摘要:

Russian Chemical Reviews 68 (8) 615 ± 636 (1999) Crystal chemistry of compounds containing mercury in low oxidation states N V Pervukhina, S A Magarill, S V Borisov, G V Romanenko, N A Pal'chik Contents n I. Introduction II. Crystal structures of inorganic compounds containing (Hg2)2+ groups III. Mixed-valence inorganic mercury compounds IV. Compounds containing polyatomic Hgxá cations (n>2) V. Monovalent mercury compounds with organic ligands VI. Mercury-containing transition metal clusters VII. Conclusion Abstract. The published data are surveyed and a comparative crystal-chemical analysis is presented for the structures of com- pounds containing mercury in low oxidation states as cluster Hgn groups with covalent Hg7Hg bonds. The geometry of com- pounds with Hg7Hg and Hg7X bonds (X=O, S, Se, N or Hal) is analysed and the types of coordination of mercury ions, the packing modes and the relationships between structural units are described.The crystallographic and crystal-chemical data for mercury compounds are given. The bibliography includes 124 references. I. Introduction It is known that mercury can exist not only in the oxidation state of +2 typical of Group II elements, but also in lower oxidation states which form polyatomic groups of the cluster type. These groups are found in inorganic complex compounds as well as in mercury-containing transition metal clusters. Diatomic groups (the so-called dumbbell-like groups), in which atoms of mono- valent { mercury 1 are bound through a covalent bond and the Hg7Hg distances vary in the range of 2.5 ± 2.6A, are most widespread.A large body of research of Hg(I) compounds confirmed the presence of the (Hg2)2+ pairs in the linear 7X7Hg7Hg7X7 fragments (X=O, N, S, Se or Hal), which contain two almost collinear sp bonds, as in the analogous { Hereinafter, by monovalent mercury compounds are meant compounds containing (Hg2)2+ dimers. N V Pervukhina, S A Magarill, S V Borisov, G V Romanenko Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences, prosp. Akad. Lavrent'eva 3, 630090 Novosibirsk, Russian Federation. Fax (7-383) 234 44 89. Tel. (7-383) 234 44 66. E-mail: pervukh@che.nsk.su (N V Pervukhina), svetlana@che.nsk.su (S A Magarill), borisov@che.nsk.su (S V Borisov), romanenk@che.nsk.su (G V Romanenko) N A Pal'chik United Institute of Geology, Geophysics and Mineralogy, Siberian Branch of the Russian Academy of Sciences, prosp.Koptyuga 3, 630090 Novosibirsk, Russian Federation. Fax (7-383) 233 27 92. Tel. (7-383) 233 29 03. E-mail: nadezhda@uiggm.nsk.su Received 14 January 1999 Uspekhi Khimii 68 (8) 683 ± 707 (1999); translated by T N Safonova #1999 Russian Academy of Sciences and Turpion Ltd UDC 548.735 615 615 624 627 629 633 635 7X7Hg7X7 fragments in Hg(II) compounds. The (Hg2)2+ pairs were found for the first time in studies of mercurous halides Hg2X2 (X=F, Cl, Br or I). These pairs were also observed in approximately twenty minerals.2 The Hg3 `triangles', in which mercury exists in the formal oxidation state of +4/3 and the Hg7Hg distance is *2.7A (in metallic mercury, the Hg7Hg distance is *3A), are less abundant.A number of compounds contain linear systems of the Hgn type (n=3, 4, ?) in which mercury atoms are bound to each other and exist in fractional oxidation states (+2/3, +1/2 or +1/3). As n increases, these compounds approximate metals in properties, and a pronounced correlation between the decrease in the charge on the mercury atom and the increase in the Hg7Hg distance (2.51 ± 2.90A) is observed. The crystal chemistry of mercury differs sharply from the crystal chemistry of its lighter analogues, viz., of zinc and cadmium. Unlike these metals, mercury can form polyatomic Hgxá n cations. Note that the (Zn2)2+ ion was found in a Zn/ZnCl2 melt 1 and the (Cd2)2+ pair was detected in the Cd2(AlCl4)2 compound (the distance between the cadmium atoms is 2.576A).3 n n There is no consensus of opinion as to the electronic structures not only of Hgxá systems, but also of simple HgX2 and Hg2X2 compounds.This is evidenced by numerous experimental and theoretical studies on the crystal and electronic structures of mercury-containing compounds and on the nature of bonding in these compounds. This heavy element with the closed shell electronic configuration 5d 106s2 `accumulates' all the factors, which hinder investigations of the electronic structures of its compounds by quantum-chemical methods. Thus, mercury is characterised by a large atomic number, the absence of unpaired electrons, the filled valence 5d and 6s orbitals, the presence of high-lying outer unoccupied 6p orbitals and a substantial influ- ence of relativistic effects on the electronic state of the mercury atom and ions.Presently, factors, which contribute to the formation of Hgxá systems, are not all revealed and the reasons for the changes in their sizes, the geometrical shape and the Hg7Hg distances are not understood.4, 5 II. Crystal structures of inorganic compounds containing (Hg2)2+ groups More than 30 crystal structures of inorganic compounds contain- ing (Hg2)2+ groups have been established. These structures belong to different types, viz., to molecular, layered or framework structures.The principal crystal-structural data for these com-616 pounds are given in Table 1, in which the compounds are placed in order of increasing complexity of their structures, viz., beginning with simple molecular structures and ending with complicated framework structures. Asystem containing the (Hg2)2+ pair and the oxygen atoms of two water molecules was found in the study 6 of the atomic arrangement in the Hg2(ClO4)2 . 4H2O compound both in aque- ous solutions at various concentrations and in the solid state. In this system, the Hg7Hg and Hg7O distances are 2.50 and 2.14A, respectively, and the remaining Hg_O distances are larger than 2.70A. Apparently, the virtually linear [H2O7Hg7Hg7OH2]2+ groups (the Hg7Hg7O angle is 178.1 8) are present both in solution and in the crystal.It was demonstrated that a change in the concentration of the solutions has no effect on the Hg7Hg bond length. In addition, the metal ¡À metal bonds in solutions (2.52 A) and in the solid state (2.50 A) differ only slightly. In the crystal structure, the [H2O7Hg7Hg7OH2]2+ groups are located parallel to the b axis (Fig. 1). Two other water molecules and the oxygen atoms of the [H2O7Hg7Hg7OH2]2+ cations and of the tetrahedral ClO¡¦4 anions are linked through hydrogen bonds (2.82A). In the study cited, mention was made of the existence of yet another hydrate, Hg2(ClO4)2 . 2H2O, which also contains the [H2O7Hg7Hg7OH2]2+ groups with the Hg7Hg and Hg7O distances of^2.48 and^2.10A, respectively.c 0 O(2) O(1) Cl O(10) O(3) O(4)O(5) b DCl, DO DHg, Figure 1. Projection of the crystal structure of Hg2(ClO4)2 . 4H2O onto the (100) plane. Hydrogen bonds are indicated by dashed lines. Analogous linear groups were found in the structures of hydrates Hg2(NO3)2 . 2H2O,7, 8 Hg2SiF6 . 2H2O (see Ref. 9) and Hg2AlF5 . 2H2O.10 Two studies were devoted to the structure of Hg2(NO3)2 . 2H2O.7, 8 Originally,7 the coordination environment about the mercury atoms in the (Hg2)2+ pairs was described as a tetrahedron. The rather short distance between the mercury atom and the oxygen atom of the water molecule is indicative of the formation of the aqua [H2O7Hg7Hg7OH2]2+ cations. In the crystal structure, the water molecules and the NO¡¦3 anions are linked through hydrogen bonds (2.29 ¡À 2.60A).The structure refinement of Hg2(NO3)2 . 2H2O8 confirmed the existence of the aqua [H2O7Hg7Hg7OH2]2+ cation. However, it was demon- strated that the coordination environment about the mercury atom is formed only by the two nearest neighbours, viz., by the mercury atom of the (Hg2)2+ pair and the oxygen atom of the water molecule. The remaining Hg_Odistances vary from 2.68 to N V Pervukhina, S A Magarill, S V Borisov, G V Romanenko, N A Pal'chik 0 b a DHg, DN, DO Figure 2. Herringbone molecular packing in the structure of Hg2(NO3)2 . 2H2O. 3.03A. Two water molecules are linked to the same oxygen atom of the NO¡¦3 group through the hydrogen bonds between the H2O molecules and the NO¡¦3 anion (2.68 and 2.70A) (Fig.2). It should be noted that the Hg7Hg and Hg7O bond lengths in the Hg2(ClO4)2 . 4H2O and Hg2(NO3)2 . 2H2O compounds are virtu- ally identical, but the [H2O7Hg7Hg7OH2]2+ fragments in Hg2(NO3)2 . 2H2O deviate significantly from linearity (the Hg7Hg7O angle is 167.5 8), which may be a consequence of the difference in the packing of these fragments in the crystal structures. 6 The structure of the Hg2SiF6 . 2H2O compound was described as a ionic structure containing the slightly nonlinear aqua [H2O7Hg7Hg7OH2]2+ cations (the Hg7Hg7O angle is 170.9 8).9 The mercury atoms each form contacts with three fluorine atoms of the octahedral SiF2¡¦ anions.The Hg7F distances vary from 2.71 to 2.87A and the remaining distances are larger than 3A. In addition, there are hydrogen bonds between the fluorine atoms and the water molecules (F_O 2.58 and 2.65A). The hydrogen bonds between the water molecules and the fluorine atoms (F_O 2.56 ¡À 2.86A) are also of great importance in the Hg2AlF5 . 2H2O compound.10 These bonds stabilise the framework formed from trans chains of the AlF6 octahedra parallel to the c axis. The quasi-linear [H2O7Hg7Hg7OH2]2+ cations are located between the chains at different heights. Therefore, the above-considered compounds containing the mercury atoms in the oxidation state of +1 and water molecules can be considered as within the ionic structures of the [Hg(H2O)]22+ cations.Early investigations of the structures of halides with compo- sition Hg2X2 (X=Cl, Br or I) have been devoted to the determination of the unit cell parameters and the atomic coor- dinates based on X-ray powder data.3 More recently, the struc- tures of Hg2X2 (X=F, Cl or Br) were refined based on single- crystal X-ray data.11, 12 The crystal structure of mercurous chloride Hg2Cl2 was determined also by neutron powder diffrac- tion analysis.13 It was confirmed that this compound has a linear molecular structure with the Hg7Hg and Hg7Cl distances of 2.5955 and 2.3622A, respectively. Longer intermolecular Hg_Cl contacts (3.2059A) were also found. The Cl_Cl distances between the adjacent linear Cl7Hg7Hg7Cl molecules along the [001] direction are 3.586 and 3.667A.The molecular character of the structure and virtually linear 7O7Hg7Hg7O7 groups were found in the study of the crystal structure of Hg2(BrO3)2.14 The (Hg2)2+ pairs are locatedTable 1. Crystallographic and crystal-chemical characteristics of low-valent mercury compounds. Compound Inorganic monovalent mercury compounds Hg2(ClO4)2 . 4H2O Hg2(NO3)2 . 2H2O Hg2(NO3)2 . 2H2O Hg2SiF6 .2H2O Hg2AlF5 . 2H2O Hg2Br2 (kuzminite) Hg2F2 Hg2Cl2 (calomel) Hg2(BrO3)2 HgReO4 Hg2(NO2)2 Hg2(NO2)2 Hg2(H2PO4)2 HgVO3 Hg2Mo2O7 Hg2Mo5O16 (Hg2)3(AsO4)2 Hg2O4 Hg2SeO4 [(Hg2)2O(NO3)](NO3) . .HNO3 [(Hg2)5(OH)4(NO3)2](NO3)4 Hg2OH(NO3)Hg2(NO3)2 Hg10(OH)4(NO3)6 Hg4(PO4)(NO3) .H2O AgHg2PO4 Hg4OPb2(NO3)6 K5Cs5[(Hg2)2WO(H2O) .. (AsW9O53)2] Hg4SbO3(OH)3 (shakhovite) Z Space group 4 Imma 2 P21/n 2 P21/n 2 P21/c 4 I4cm I4/mmm 2 I4/mmm 2 I4/mmm 24 C2/c 4 P21/c 2 P21/c 2 P21/c P21/n P1 7 22 P1 712 P21/c 2 P21/c 2 P2/c 2 P2/c 8 Aba2 P1 718 Cc2a P1 714 P21/n 4 Pbam Fd3m P1 7 842 Im Unit cell parameters a b c a b g 7.55 20.59 7.59 6.30 7.52 8.64 6.256(3) 7.506(4) 8.633(3) 8.922(2) 8.601(2) 5.642(1) 7.241(6) 9.353(5) 9.353(5) 4.663(1) 11.133(2) 4.663(1) 3.6700(4) 3.6700(4) 10.901(2) 4.4795(5) 4.4795(5) 10.9054(9) 8.595(2) 4.470(1) 18.806(7) 5.070(1) 15.204(2) 5.663(1) 6.277(1) 4.4145(9) 10.333(2) 6.301(2) 4.435(1) 10.344(2) 6.0754(5) 14.5034(7) 4.7280(4) 8.588(1) 4.752(1) 3.592(1) 8.038(2) 7.144(2) 7.097(2) 5.513(1) 14.289(2) 9.139(1) 15.64(3) 5.08(1) 8.73(2) 6.2802(9) 4.4273(5) 8.367(2) 6.3507(8) 4.5870(7) 8.499(2) 9.354(2) 11.222(8) 20.178(2) 7.657(3) 9.091(4) 9.990(3) 9.358(3) 11.217(3) 20.171(5) 7.659(2) 9.099(5) 9.994(5) 5.952(8) 8.258(3) 18.38(9) 6.152(2) 8.614(2) 9.256(2) 15.412 15.412 15.412 16.88(1) 18.82(1) 28.99(1) 5.433(1) 4.871(1) 15.098(3) 103.8 103.8(1) 123.8(2) 107.19(3) 110.17(1) 108.83(1) 108.74(2) 92.172(7) 79.60(1) 89.30(1) 144.1 88.32(1) 66.09(1) 166.45(1) 324.4 65.89(1) 110.65(1) 128.4(3) 91.76 90.98 94.05(3) 101.25(3) 109.75(3) 634.9 78.70(3) 109.83(5) 635.5 85.98(4) 91.2(1) 84.36(8) 78.25(6) 8818 78.49(1) 98.86(2) V /A3 1162.7 397.5 393.7 355.9 633.4 242.1 218.83 690.2 409.7 271.03 273.7 416.3 673.7 543.6 232.5 247.5 2118 2117 903.2 7 7 7 2.608 3660.8 394.8 Bond length /A dexp dcalc /g cm73 Hg7Hg 3.839 7 2.50 4.683 7 2.54 4.733 4.785 2.508 2.495 5.37 5.41 7 2.511 5.86 7.696 7 2.49 7 2.51 9.93 7.162 7 2.5955 2.507 6.20 6.32 7 2.506 7.31 2.516 6.20 6.04 7 2.520 5.99 2.499 4.70 4.75 6.901 7 2.543 7 2.522 7.22 5.604 7 2.474 2.535 9.05 9.06 2.500 7.05 7.10 2.51 7.14 7.27 2.502 ± 2.513 6.306 6.30 2.495 ± 2.511 6.398 6.31 2.499 ± 2.505 6.30 6.31 2.488 ± 2.505 6.20 6.39 2.508 ± 2.532 7.10 7.19 5.823 7 2.458 2.446 ± 2.545 4.90 4.86 7 2.543 8.60 Hg7Xa 2.14 2.15, 2.40, 2.42 2.13 2.68 ± 3.03 2.20, 2.713 ± 2.894 170.9 2.144 2.827 ± 2.894 2.71, 3.32 2.133 2.3622, 3.2059 2.16 2.69, 2.66 2.24 ± 2.62 2.244 2.224 2.577 ± 2.955 2.142, 2.514 2.112 2.708 ± 2.946 2.079, 2.139 2.735 ± 3.112 2.208 2.553 ± 3.113 2.16 ± 2.23 2.42 ± 2.71 2.24, 2.49 ± 2.93 2.21, 2.50 ± 2.90 2.12 ± 2.31 2.46 ± 2.96 2.09 ± 2.22 2.61 ± 2.87 2.142 ± 2.364 2.488 ± 2.733 2.052 ± 2.266 2.602 ± 2.966 2.11 ± 2.21 2.45 ± 2.85 2.224 ± 2.348 2.108 2.16, 2.34 2.135, 2.160, 2.514 ± 2.193 The Hg7Hg7X Ref.angle a 6 178.1 7 160 8 167.5 9 10 173.0 180 (Hg7Hg7Br) 11 180 (Hg7Hg7F) 12 180 (Hg7Hg7Cl) 13 14 174.0 15 159.4 16 174.2 17 173.3 18 167.2 19 174.1 20 167.3, 178.8 21 152.7 23 146 ± 157 24 165 24 160 27 145.9 ± 173.3 27 166.1 ± 178.5 29 140.5 ± 170.8 30 165.9 ± 178.8 31 147.8 ± 168.1 32 101.2, 140.1, 142.9 33 34 161.7 35 155.0, 166.3Table 1 (continued).Z Space Compound group 24 19.009(5) C2/c Hg3OCl (poyarkovite) 16 16.036(3) 16.036(3) 16.036(3) Ia3d (Hg2)3O2Cl2H (eglestonite) Hg2TeO3 (magnolite) 2 Pbm2 Hg6Si2O7 (edgarbaileyite) 2 C2/m (Hg2)8(Ni,Mg)6(CO3)12(OH)127 P63 1 7(H3O)8(H2O)x (x*3) (szymanskiite) Mixed-valence mercury compounds 8 C2/c Hg2OI [Hg2(OHg)2](NO3)2 2 P21/c 2 P21/a Hg4O2(NO3)2 Hg8O4Br3 P21/n P1 7 4 Hg2ReO5 4 Hg5Re2O10 (I) 2 P21/b 4 P21/c Hg5Re2O10 (II) Hg2VO4 8 P21/n Hg9P5I6 4 P21/c P1 72 Hg5CrO5S2 (deanesmithite) Hg5CrO6 (wattersite) 4 C2/c HgHg6[Cl(OH)]2O3 (hanawaltite) Pbma 44 C2/c Hg4O2Cl2 (terlinguaite) Hg3(AsO4)Cl (kuznetsovite) 4 P213 Hg9(AsO4)4 6 R3c Compounds containing (Hg3)2+ groups and Hgn chains Hg3(AsF6)2, 2 P21/c (Hg3)2+ group Hg3(AlCl4)2, 4 P21/c (Hg3)2+ group Hg3(NbF5)2(SO4), 8 Fdd2 (Hg3)2+ group Hg3(TaF5)2(SO4), 8 Fdd2 (Hg3)2+ group Hg4(Ta2F11)2, 4 I2/c (Hgn)2+ chain Hg4(AsF6)2, 2 P21/c (Hgn)2+ chain Unit cell parameters a b c a b g 9.018(4) 16.848(9) 3.749(1) 5.958(1) 10.576(2) 5.991(2) 7.678(2) 11.755(3) 17.3984(7) 17.3984(7) 6.0078(4) 6.701(5) 6.981(5) 17.603(8) 6.659(2) 11.578(5) 5.532(3) 5.533(1) 6.664(1) 11.580(2) 6.8554(9) 6.3033(9) 31.093(3) 9.015(2) 114.11(1) 101.64(2) 91.19(2) 569.7 8.948(2) 7.952(2) 7.981(5) 11.538(7) 6.401(5) 8.615(1) 12.009(2) 12.039(2) 3.673(1) 16.503(1) 14.255(1) 13.112(5) 12.486(2) 17.031(3) 8.1287(8) 9.4916(7) 6.8940(4) 100.36(1) 110.16(1) 82.98(1) 490.13 6.603(1) 11.274(2) 11.669(2) 6.460(1) 11.777(2) 13.891(3) 9.466(4) 5.904(3) 11.953(4) 8.379(3) 16.603(1) 7 10.830(2) 8.551(6) 11.282(10) 5.981(5) 7.1321(2) 15.0468(3) 14.1771(4) 9.176(4) 18.068(6) 15.734(5) 9.153(2) 18.078(7) 15.705(4) 7.528(3) 14.714(8) 18.556(8) 9.85(6) 5.489(2) 11.633(4) 110.81(3) 111.73(3) 101.61(2) 98.84(3) 98.82(1) 96.09(1) 98.87(19) 97.15(1) 89.99(1) 119.90(2) 98.19(2) 105.59(6) 91.16(7) 99.05(3) 91.72(4) 92.20(4) V /A3 dexp dcalc /g cm73 9.643 7 2696 8.652 7 4123.7 8.108 7 236.2 7 9.10 502.3 7 4.86 1574.9 120 7 8.96 807 7.552 7.52 421.4 7.5 7.54 422 7 9.49 1336 7 7.78 8.755 7 582.4 7 8.25 1235.8 7.934 7 864.1 7.472 7 2419.0 7 8.14 8.891 7 859.8 7 9.51 1056.9 9.40 9.35 643 8.763 7 588.3 9.038 7 2585.4 7 5.67 577.1 3.95 4.16 1502.5 5.467 2.562 5.49 2608.6 6.388 6.387 2.554 2599 7 6.285 2.593, 2.630 2054 7 6.24 628.5 Bond length /A Hg7Xa Hg7Hg 1.96 ± 2.30, 2.60 2.503 ± 2.565 2.818 ± 3.043 (Cl) 2.165 2.516 3.010 ± 3.095 (Cl) 2.06, 2.69 ± 3.00 2.532 2.12, 2.21 2.522, 2.524 2.41 ± 2.86 2.099 ± 2.144 2.494, 2.513 2.34 ± 2.44 2.141 2.534 2.16 2.510 2.136 2.510 2.10 ± 2.24 2.517 ± 2.557 2.135, 2.143 2.521 2.14, 2.19 2.546 2.102 ± 2.258 2.520, 2.508 2.20 2.536 2.452 (Hg7P) 2.541 3.568 ± 3.675 (Hg7I) 2.11, 2.352 ± 2.442 171.3 (Hg7Hg7S) 2.536 (Hg7S) 2.10 ± 2.16 2.526 1.93 ± 2.30 2.526, 2.56 2.703, 2.587(Cl) 2.234, 2.462, 2.17 ± 2.28 2.675 2.142 ± 2.343 2.662 ± 2.696 (Hg7Hg7Hg) 2.38 2.552 2.83 ± 2.96 2.517, 2.551 2.562 (Cl) 2.562 2.276 (O) 2.809 ± 2.990 (F) 2.27 (O) 2.76 ± 3.00 (F) 2.74 ± 2.82 3.033 (Hg_Hg) 2.97 ± 3.23 2.71 ± 2.95 2.588, 2.620 3.06 ± 3.34 2.985 (Hg_Hg) The Hg7Hg7X Ref.angle a 36 137.8 ± 173.2 37 162.7 38 167.0 39 177.2, 164.9 40 136.3 ± 175.2 46 174.6 27 177.9 48 178.1 49 165.1 ± 172.4 15 170.4, 173.1 52 164.0, 173.9 53 145.7 ± 177.9 19 153, 173 168.7 (Hg7Hg7P) 55 57 167.6 58 153.3, 169.5 59 175.4, 177.0 60 (Hg7Hg7Hg) 44 60 (Hg7Hg7Hg) 60 59.5 ± 60.8 180 (Hg7Hg7Hg) 63 168.9 (Hg7Hg7F) 174.4 (Hg7Hg7Hg) 66 172.8, 176.6 (Hg7Hg7Cl) 166.6 (Hg7Hg7Hg) 67 174.8 (Hg7Hg7F) 166.2 (Hg7Hg7Hg) 67 177.2 (Hg7Hg7Hg) 67 165.1 (Hg7Hg7F) 177.3 (Hg7Hg7Hg) 68 141.3 (Hg7Hg7F)Table 1 (continued).Compound Hg2.86AsF6, (Hgn)2+ chain Hg2.86(AsF6)0.953, (Hgn)2+ chain Hg37dSbF6 [d=0.10(2)], (Hgn)2+ chain Hg37dTaF6 [d=0.116(4)], (Hgn)2+ chain Hg37dNbF6 [d=0.119(2)], (Hgn)2+ chain Hg37dSbF6 [d=0.134(1)], (Hgn)2+ chain Hg37dTaF6 [d=0.142(2)], (Hgn)2+ chain Hg3NbF6, layer (Hg)n Monovalent mercury compounds with organic ligands Hg2(L1)2(ClO4)2 Hg2(L2)2(ClO4)2 Hg2(L3)2(ClO4)2 Hg2(L4)2(ClO4)2 Hg2(L5)2(ClO4)2 .H2O Hg2(L6)(ClO4)2 Hg2(L7)4(ClO4)2 Hg2(L8)4(ClO4)2 Hg2(Ph2Se)4(ClO4)2 (yellow form) Hg2(Ph2Se)4(ClO4)2 (red form) Hg2(Ph3PO)6(ClO4)2 Hg2Phen(NO3)2 Hg2(L9)2(NO3)2 Hg2(L10)2(NO3)2 Hg2(L11)2(NO3)2 Z Space group I41/amd 4 I41/amd 4 I41/amd 4 I41/amd 4 I41/amd 4 I41/amd 4 I41/amd 4 P3 71m 12 P21/c 8 C2/m 2 P21/n 2 I2/m P21/n P1 7 422 P21/c P1 722 P21/n P21/n 2 P1 71 P1 724 C2/c 4 C2/c 2 P2/c Unit cell parameters a b c a b g 7.538(4) 12.339(5) 7.538(4) 7.549(5) 12.390(9) 7.549(5) 7.711(2) 12.641(2) 7.711(2) 7.711(1) 12.714(2) 7.711(1) 7.692(1) 12.679(2) 7.692(1) 7.655(1) 12.558(1) 7.655(1) 7.634(1) 12.610(1) 7.634(1) 120 7.68(7) 5.021(1) 5.02(1) 98.1(1) 5.509(5) 15.110(10) 11.630(10) 92.4(1) 5.04(1) 22.92(4) 16.49(2) 105.95(1) 5.164(1) 11.224(1) 18.639(3) 99.06(2) 7.142(1) 10.629(1) 16.841(1) 95.42 5.979 25.794 15.913 83.04(13) 66.53(4) 1518.02 69.60(5) 10.206(2) 12.006(8) 14.411(6) 96.20(1) 11.729(1) 10.896(1) 18.392(2) 85.8(1) 115.2(1) 14.00(2) 12.76(2) 8.68(1) 92.60 13.910(8) 14.575(9) 12.109(6) 98.20 14.391 14.462 11.609 82.3(1) 120.0(1) 16.05(2) 14.47(2) 12.55(1) 93.0(1) 98.6(1) 10.58(3) 10.55(3) 6.83(2) 100.35(6) 10.628(9) 10.219(8) 18.236(15) 100.89(1) 5.273(1) 16.956(4) 26.969(4) 95.138(12) 8.6819(5) 5.3696(6) 19.7645(8) V /A3 dexp dcalc /g cm73 7.224 7 701.1 7.06 7.04 706.1 7 7.22 751.6 7 7.68 756.0 7 6.95 750.2 7.314 7 735.9 7.844 7 734.9 7 8.0 167.6 7 2.80 958 2.81 2.89 1904 2.65 2.75 1038.6 2.51 2.52 1262.5 2.738 7 2443.2 2.294 2.31 1.77 1.78 2336.7 2.35 2.34 97.5(1) 1390 2.27 2.08 2452 2.27 2.13 2392 1.50 1.51 95.2(1) 2499 3.04 3.15 744 97.6(1) 2.61 2.67 1948.34 7 2.56 2368.0 2.75 2.70 917.74 Bond length /A Hg7Xa Hg7Hg 2.99 2.64 3.24 (Hg_Hg) 2.87 2.98 2.86, 2.98 2.66 3.22 (Hg_Hg) 2.86, 2.983 2.67 3.239 (Hg_Hg) 2.86, 2.97 2.67 3.222 (Hg_Hg) 2.81, 2.956 2.67 3.210 (Hg_Hg) 2.81, 2.937 2.67 2.937 (Hg_Hg) 3.2 2.90 2.16 (N) 2.498 2.21 (N) 2.487 2.03 (N) 2.511 2.15 (N) 2.5177 2.16, 2.21 (N) 2.501 2.20 (N); 2.506 2.63, 2.69 (O) 2.227 (N) 2.5084 2.476 (N) 2.19 (O) 2.523 2.34 ± 2.56 2.701, 2.802 (Se) 2.5579 2.705 (O) 2.653, 2.919 (Se) 2.553 2.626 (O) 2.29 ± 2.43 (O) 2.522 2.30 ± 2.48 (N) 2.516 2.227 ± 2.590 (O) 2.168 (N) 2.551 2.192 (N) 2.517 2.233 (N), 2.658 (O) 164.3, 113.9 2.518 The Hg7Hg7X Ref.angle a 180 (Hg7Hg7Hg) 70 180 (Hg7Hg7Hg) 71 7 72 7 73 7 73 7 74 7 74 7 75 79 176.0 80 167.4 81 174.4 82 180 83 162.8, 171.5 84 170.3, 172.9 85 153.9, 118.4 87.5 (N7Hg7N) 87 105.9 ± 159.9 88 116.4, 141.1 (Hg7Hg7Se) 103.3 (Hg7Hg7O) 100.56 (Se7Hg7Se) 89 104.4, 152.0 (Hg7Hg7Se) 109.6 (Hg7Hg7O) 102.7 (Se7Hg7Se) 90 116.0 ± 140.0 79.4 ± 86.4 (O7Hg7O) 91 131.7, 136.7, 171.3 92 164.4 93 160.5 94Table 1 (continued). Compound Hg2(L12)2(NO3)2 Hg2(L13)2(NO3)2 [Hg2(L14)2]2(NO3)2 Hg2(L15)2(H2O)2 Hg2(L16)2 Hg2(L17)2 Hg2(L17)2(H2O)2 Hg2(L18)2 Hg2(L19)2 Hg2(CF3CO2)2 Hg2[C(CN)3]2 Hg2(C7NH4)2 Hg2(L20)2(AlCl4)2 .C7H8 Mercury-containing transition metal clusters Hg2Co2[N(C2H4PPh2)]3 .THF {Hg2Pt6[(Ph2P)2(CH2)6]37 7(C8H9NC)6} .2(C6H6) [(Ph3P)2N]2[Hg2Os18(CO)20C2] [(Ph3P)2N]4[Hg2Os18(CO)42C2] . .CH2Cl2 {Hg3[(Ph2P)2CH2]3}(SO4)2 . 1.5H2O P21/n P1 7[(Ph3P)2N]2[Hg3Ru18C2(CO)42] . .CH2Cl2 (C36H30NP2)2[Hg3Os9(CO)21C2] . .CH2Cl2 Hg2Ag[(Ph2P)2CH2]3(CF3SO3)3 [Nb(Z-C5H5)2{HgS2CN(C2H5)2}3] P21/n I4 7[(Z5-CH3C5H4)Mn(CO)2Hg]4 [(Z5-C5H5Re(CO)2Hg]4 [(C12H36)3Rh]4Hg6 [(C8H18P)2Pt]4Hg6 [Hg9Co6(CO)18] . 2(C3H6O) Note. Samples of natural and synthetic (italicised) minerals were studied; the unit cell parameters a, b and c are given in A Ê , the angles a, b, g and Hg7Hg7X are given in deg.a For inorganic monovalent mercury compounds, mixed-valence mercury compounds and compounds containing (Hg3)2+ groups and Hgn chains X=O or Hal; for monovalent mercury compounds with organic ligands, X=N, O, Se or S; for mercury-containing transition metal clusters, X=Hg, Pt, Os or Ru. Z Space group P1 724 P2/c P2/n 2 C2/c 4412 C2/c P1 7 P2/n C2/c P1 7 8142 C2/c P1 7 P21/n 24 P21/c P1 72 C2/c 4 P1 71 P17 141 P1 71 P21/n 4428444 C2/c Ccmm C2/c P21/c Unit cell parameters a b c a b g 5.4878(1) 8.4085(1) 9.6062(1) 92.599(3) 94.763(3) 89.614(3) 441.283 2.865 7 6.970(5) 15.205(8) 11.185(8) 8.760(8) 11.755(9) 10.798(8) 9.989(9) 11.788(9) 13.527(13) 6.057(9) 14.857(3) 23.624(4) 6.985(3) 114.80(15) 92.69(4) 86.41(7) 432.80 7.347(3) 9.311(9) 7.588(2) 10.345(4) 11.944(3) 26.330(20) 6.254(2) 12.90(10) 80.77(2) 5.970(1) 15.774(6) 5.038(1) 8.230(5) 9.337(5) 14.866(5) 5.2794(1) 9.9297(1) 11.3376(2) 71.004(4) 76.459(2) 74.601(4) 534.647 3.611 7 9.9193(1) 5.6912(2) 13.3806(1) 21.160(10) 10.951(7) 18.80(10) 25.691(9) 13.387(5) 13.471(4) 119.56(8) 15.120(8) 31.01(3) 56.86(8) 18.711(4) 16.379(3) 11.724(2) 111.242(2) 84.284(1) 105.994(2) 3220.08 89.23(2) 117.24(2) 94.03(2) 5053.91 19.121(2) 16.638(4) 17.676(4) 15.069(2) 24.025(2) 22.405(2) 19.042(4) 15.729(3) 15.197(3) 115.59(2) 19.022(4) 15.737(3) 15.205(3) 115.66(2) 15.256(3) 28.028(8) 21.863(3) 12.302(10) 18.385(11) 16.077(5) 7.683(1) 15.959(2) 15.959(2) 20.036(14) 16.143(8) 22.111(13) 12.909(2) 25.274(4) 25.176(4) 12.738(3) 48.692(6) 16.602(3) 14.341(6) 21.024(6) 18.543(9) V /A3 Bond length /A dexp dcalc /g cm73 Hg7Hg 2.524 2.541 3.55 3.67 1178.9 96.0(6) 1.972 7 2.549 1039.86 110.74(4) 3.151 7 2.494 1588.22 94.350(9) 2.500 2.80 2.89 1714.86 126.23(7) 2.515 2.80 2.86 2.522 2.80 2.87 903.74 105.44(6) 2.519 4.03 3.96 1893.4 116.94(3) 2.514 3.151 3.12 86.42(2) 84.38(2) 465.5 4.412 4.391 2.505 943.8 124.4(2) 2.506 3.007 7 2.503 754.63 92.544(2) 1.823 7 2.515 4209.9 104.9(1) 1.578 7 2.651 97.51(8) 87.25(7) 3994.48 2.872 (Pt7Pt) 2.878 ± 2.993 1.545 7 16673 141.29(6) 2.656 ± 2.672 2.744 (Os7Os) 2.636 ± 2.907 3.147 7 2.743 ± 3.038 2.820 (Os7Os) 2.474 ± 2.898 2.326 7 2.748 ± 3.092 1.620 7 2.764 ± 2.802 8092.8 93.88(1) 7 2.919 ± 2.934 2.66 68.51(2) 115.46(2) 2983.18 2.733 ± 3.010 (Ru7Ru) 2.910 7 2.919, 2,931 68.32(2) 115.45(3) 3609.39 1.500 7 2.660 9342 92.14(1) 2.441 7 2.901, 2.883 3454.66 108.18(5) 7 7 2.888 2.64 1956.8 7 7 2.92 3.85 78.66(5) 7 7 3.131 ± 3.149 2.05 8213.9 2.037 7 3.081 ± 3.274 10255.47 95.16(2) 7 3.066 ± 3.216 3.11 5574 94.50(4) Hg7Xa 2.209 (N) 2.496, 2.584 (S) 2.516 (O) 2.469, 2.489 (S) 2.636, 2.652 (O) 2.203 (N), 2.621 (O) 165.7 2.179 (N) 2.187 (N), 2.68 (O) 169.6, 107.3 2.201 (N) 2.711, 2.715 (O) 2.08, 2.16 (O) 2.13 (O) 2.14 (O) 2.287, 2.508 (N) 2.207 ± 2.560 (N) 2.416, 2.672 (C) 2.429, 2.444 72.640 ± 2.734 2.678 ± 2.762 2.805, 2.853 2.777 ± 2.808 2.640 2.74 2.690 ± 2.724 2.671 ± 2.876 2.521 ± 2.609 The Hg7Hg7X Ref.angle a 95 169.5 96 173.5, 138.7 97 162.0, 163.3 101.3, 113.0 98 99 170.7 99 99 172.8 89.7, 107.1 100 171. 175 101 173.9 102 166.6 103 123.9, 121.3 123.0 ± 140.0 104 162.2, 116.5 7 105 106 107 108 109 110 111 112 114 115 116 117 118 119 120Crystal chemistry of compounds containing mercury in low oxidation states nearly parallel to the a axis. The distances between the nearest pairs are 4.5A. The Hg7O distance in the 7O7Hg7Hg7O7 group is 2.16A. In addition, there are Hg_O distances (2.66 and 2.69A). Taking into account the latter contacts, the coordination environment about the mercury atoms can be described as a distorted tetrahedron.The Hg2(BrO3)2 molecules are linked in linear chains along the c axis through weak O_O contacts (2.66A). The rows of the mercury pairs alternate with double rows of the BrO¡¦3 anions along the a axis (Fig. 3). The effect of the mercury atoms on the BrO¡¦3 groups consists in the increase in the distance between the bromine atom and the oxygen atom bound to the mercury pair. This distance is 1.76A, whereas two other Br7O bond lengths are 1.64 and 1.65A. a c 0 DHg, DBr, DO Figure 3. Projection of the crystal structure of Hg2(BrO3)2 onto the (010) plane. The O_O contacts are indicated by dashed lines. The crystal structure of HgReO4 consists of discrete (O3Re7O7Hg7Hg7O7ReO3) groups, which are substan- tially nonlinear (the Hg7Hg7O angle is 159.4 8), apparently, due to the type of the molecular packing in the monoclinic unit cell.15 The mercury atoms each form contacts with the oxygen atoms of other structural units (the distances are larger than 2.49 A) along with the short Hg7O bonds.2 The virtually linear groups were also found in the first stucturally studied monovalent mercury nitride, Hg2(NO2)2, consisting of the planar centrosymmetrical molecular NO27Hg7Hg7NO2 groups.16 The nonbonded Hg_O interac- tions (2.84 and 2.93A) are analogous to those found by Grdenic.7 Taking into consideration these contacts, the coordination num- ber of the mercury atom increases to 4. In the crystal structure of Hg2(NO2)2, the molecules are packed in a herringbone fashion.7, 8 The structure of this compound was also studied by Ohba and coworkers.17 In this study, the Hg_O bond (2.577A) was found along with the Hg7O (2.24A) bond, i.e., both oxygen atoms of the NO¡¦ group are bound to the mercury atoms of the (Hg7Hg)2+ cations to form a planar centrosymmetrical mole- cule.In addition, Hg_O contacts (2.826A) between the adjacent molecules were revealed. The authors believed that the yellow colour of the crystals is associated with the bridging function of the (Hg2)2+ pairs. A rather short Hg7Hg distance (2.499A) was observed in the structure of Hg2(H2PO4)2.18 Each mercury atom has an oxygen atom as the nearest neighbour at a distance of 2.14A.The 7O7Hg7Hg7O7 fragment is nonlinear (the Hg7Hg7O angle is 167.2 8). The distances between the mercury atom and the remaining oxygen atoms are larger than 2.5A. The structure of the complex consists of the discrete Hg2(H2PO4)2 molecules linked in a three-dimensional framework via hydrogen bonds (O_O 621 2.52 ¡À 2.79A). The herringbone molecular packing in the crystal of the complex is analogous to those observed in anhydrous Hg2(NO2)2 (see Refs 16 and 17) and its dihydrate Hg2(NO2)2 . 2 . 2H2O.8 What the crystal structures of the two known mercurous vanadates, viz., HgVO3 and the mixed-valence Hg2VO4, have in common is a distorted five-vertex coordination polyhedron about the vanadium formed by the oxygen atoms.19 In both structures, the polyhedra of the vanadium atoms are linked via shared edges to form infinite [(VO3)7]n chains.In the structure of HgVO3, these chains are linked through the (Hg2)2�¢ pairs in two-dimensional corrugated infinite (Hg2)2�¢ n [(VO3)7]2n layers, which are linked via weak interlayer Hg_O contacts (2.71 ¡À 2.95A), unlike the mixed- valence Hg2VO4 compound, in which the [(VO3)7]n chains do not form strong bonds with the mercury atoms. Only three mercury molybdates were structurally character- ised. The compound HgMoO4 contains the divalent mercury atom. The Hg2Mo2O7 and Hg2Mo5O16 polymolybdates contain the (Hg2)2+ ions. The layered structures of Hg2Mo2O7 (see Ref. 20) and Hg2Mo5O16 (see Ref. 21) are based on the MoO4 tetrahedra linked in Mo2O7 groups and Mo5O16 fragments, respectively.The coordination environment about the molybde- num atoms is a distorted octahedron. In both compounds, the Mo octahedra are linked in two-dimensional infinite layers via shared vertices and edges. The layers are separated by the (Hg2)2+ pairs (Fig. 4). In the structure of Hg2Mo2O7, the Hg7Hg and Hg7O distances have standard values, whereas the Hg7Hg bond in Hg2Mo5O16 (2.474A) is rather short and the 7O7Hg7Hg7O7 fragments deviate significantly from line- arity (the Hg7Hg7O angle is 152.7 8). Noteworthy is the similarity of the structures of Hg2Mo5O16 and Cs2Mo5O16.22 4 4 In the crystal structure of the synthetic analogue of the mineral chursinite (Hg2)3(AsO4)2 (see Ref. 23), the (Hg2)2+ cations and the AsO3¡¦ anions are packed in such a manner that three of the four oxygen atoms of the AsO3¡¦ groups are bound to three different mercury pairs (the Hg7O distances are 2.16, 2.22 and 2.23A) to form puckered layers.The fourth oxygen atom is bound to three mercury atoms of the adjacent layer (the Hg_O distances are 2.48, 2.46 and 2.71A) and has a distorted tetrahedral coordination, the As7O distance with this oxygen atom (1.78A) being larger than the remaining three As7O distances (the average value is 1.68A). These characteristic groups are linked to each other along the a axis through Hg_O contacts (2.68 and 2.42A) and along the c axis through Hg_O contacts (2.47A). Taking into account all interactions, the structure of (Hg2)3(AsO4)2 can be considered as a three-dimensional frame- work (Fig.5). It should be noted that the 7O7Hg7Hg7O7 fragments are substantially nonlinear (the Hg7Hg7O angles are 146 ¡À 1578). c 0 Hg(2) Hg(1) b DHg, DMo, DO Figure 4. Crystal structure of Hg2Mo2O7.622 a Hg(3) O(2) O(3) O(4) Hg(2) As Hg(1) O(1) c 0 DHg, DAs, DO Figure 5. Projection of the crystal structure of (Hg2)3(AsO4)2 onto the (010) plane. The Hg_O contacts are indicated by dashed lines.4 The mercury pairs, which are linked in infinite 7O7Hg7Hg7O7Hg7Hg7O7 chains via the XO2¡¦ groups (X=S or Se), were observed in the isostructural Hg2SO4 and Hg2SeO4 compounds.24 The chains intersect the unit cells along the diagonals nearly parallel to the ac planes.In Hg2XO4, there are Hg_O contacts (2.49 and 2.50A in Hg2 SO4 and Hg2SeO4, respectively), which link chains. The 7O7Hg7Hg7O7 frag- ments deviate from linearity (the Hg7Hg7O angles are 1658 and 1608 in Hg2SO4 and Hg2SeO4, respectively). No noticeable changes in the size and no distortions of the XO2¡¦ 4 tetrahedra are observed in the structures. More than 30 compounds were found and described in the ternary Hg2O7N2O57H2O system.25 In the studies devoted to the hydrolysis products of nitrate Hg2(NO3)2 . 2H2O, 26 the authors confirmed the existence of only three low-valent mer- cury oxonitrates, viz., [(Hg2)2O(NO3)]NO3 .HNO3 and [(Hg2)5(OH)(NO3)2](NO3)2 containing monovalent mercury and the mixed-valence [(Hg)2(OHg)2](NO3)2 compound.In spite of the difficulties associated with the preparation of single crystals of these compounds, their structures were studied by X-ray diffraction analysis. 27 In the structure of [(Hg2)2O(NO3)]NO3 .HNO3, three (Hg2)2+ pairs are linked toer through the oxygen atoms (the Hg7O distances are 2.12, 2.19 and 2.31A) to form a planar (the height is 0.31A) trigonal pyramid with the O7Hg7O angles varying from 112.9 to 123.58. The analogous function of the oxygen atom was pointed out in the structures of mercury(II) oxochloride Hg3OCl4 (see Ref. 28), the mineral eglestonite (Hg2)3Cl3O2H (see Ref. 3) and in a number of other mercury compounds. The structure of [(Hg2)2O(NO3)]NO3 .HNO3 as a whole consists of infinite mer- cury-oxygen chains linked in a three-dimensional framework through the NO¡¦3 ions, which coordinate the mercury atoms (the Hg_O contacts are in the range of 2.45 ¡À 2.96A).The hydrogen atom was not located in the structure refinement of this com- pound. Based on the known data on the structures of the oxonium mercury salts, the authors 27 suggested that HNO3 exists as a molecule of solvation linked to the nitrate ion through a hydrogen bond (O7H_O, 2.81A). The structure of this compound was more accurately established by an independent research group .29 The position of the hydrogen atom of the hydroxy group was revealed. This group is coordinated to three (Hg2)2+ pairs (O7H, 1.26A) (Fig. 6). As a result, the structure is additionally stabilised through weak hydrogen bonds between the oxygen atoms of the hydroxy groups and the adjacent nitrate ions (Hg_O, 2.803 ¡À 2.863A).Based on this fact, the authors 29 proposed that the formula of the compound should be written as Hg2OH(NO3) . Hg2(NO3)2 . N V Pervukhina, S A Magarill, S V Borisov, G V Romanenko, N A Pal'chik Hg(1) Hg(3) Hg(4) Hg(2) DHg, DN, DO, DH Figure 6. Fragment of the structure of Hg2OH(NO3) . Hg2(NO3)2. 3 The structure of the [(Hg2)5(OH)(NO3)2](NO3)4 compound contains the finite cationic [(Hg2)5(OH)(NO3)2]4+ chains linked via weak van der Waals interactions between the adjacent mercury and oxygen atoms (Hg_O, 2.642 and 2.745A).27, 30 The chains form ribbons extended along the [100] direction. The 7O7Hg7Hg7O7 fragments are virtually linear.The coordi- nation environment about the mercury atoms involves the addi- tional NO¡¦ anions (Hg_O, 2.763 ¡À 2.887A), which are responsible for the formation of a loose framework. . 4 The structure of mercurous nitrophosphate Hg4PO4NO3 . H2O is built of the PO3¡¦ and NO¡¦3 anions and the water molecules bound to the (Hg2)2+ pairs, which form zigzag chains (the Hg7Hg distances are 2.508 and 2.532A; the Hg7O distances range from 2.11 to 2.21A; the Hg7Hg7O angles vary from 147 to 1688). These chains are linked in a three-dimensional framework through additional bonds.31 No significant changes in the size and configuration of the anions in the crystal were observed. 4 The isostructural monophosphates and monoarsenates of silver and monovalent mercury were prepared as early as 1909.However, the crystal structure of AgHg2PO4 was established only in 1978.32 The structure of the latter compound consists of the tetrahedral PO3¡¦ anions and the Ag7Ag (2.824A) and Hg7Hg pairs (2.608A). Interestingly, this structure does not contain the linear 7O7M7M7O7 fragments (M=Ag or Hg) typical of the above-considered compounds and each mercury atom is coordinated by three oxygen atoms of different PO4 tetrahedra with elongated Hg7O bonds (2.224 ¡À 2.346A). Therefore, the coordination environment about the mercury atoms in the Hg7Hg dimer is a tetrahedron (Hg+3O). Each silver atom is coordinated by two oxygen atoms (Ag7O, 2.289A). The Hg7Hg and Ag7Ag dimers are in the mutually perpendicular arrange- ment and are rather closely spaced (the Hg7Ag distances are 2.840 and 2.941A). These data suggest the existence of the tetrahedral Ag2Hg2 clusters.The three-dimensional (Hg4O2+)n framework of hexagons formed by the 7O7Hg7Hg7O7 fragments (Hg7Hg, 2.458A; Hg7O, 2.108A) was found in the crystal of the Hg4OPb2(NO3)6 compound.33 The Pb2+ ions occupy the cavities of the framework and six statistically disordered NO¡¦3 groups act as bidentate ligands with respect to Pb2+ (Pb7O, 2.77 ¡À 2.89A). The Hg4OBa2(NO3)6 compound isomorphous to Hg4OPb2(NO3)6 was also obtained. K5Cs5[(Hg2)2WO(H2O)(AsW9O53)2] Heteropolytungstate was synthesised and structurally characterised for the first time in the study.34 In this complicated structure, both [As2W19Hg4O67(H2O)]¡¦10 polyanions of one asymmetrical unit contain two (Hg2)2+ pairs, in which each mercury atom is bound to two oxygen atoms (the Hg7O distances vary from 2.16 to 2.34A). All eight mercury atoms of the asymmetrical unit form a distorted cube, whose vertices alternately correspond to theCrystal chemistry of compounds containing mercury in low oxidation states covalent Hg7Hg bonds (2.446 ¡À 2.545A) and the Hg_Hg distances (3.303 ¡À 3.796A). The structures of a series of mercury minerals containing the (Hg2)2+ pairs were analysed in detail.2 These structures are also characterised by three-dimensional frameworks. Thus, in shakho- vite Hg4SbO3(OH)3, the O_O contacts (2.618 ¡À 2.932A) between the oxygen atoms of the adjacent SbO6 octahedra link these octahedra in layers parallel to the (001) plane, which, in turn, are linked in a three-dimensional framework through the (Hg2)2+ pairs (Fig. 7).35 b Figure 7.Projection of the crystal structure of shakhovite Hg4SbO3(OH)3 onto the (100) plane. The O_O and Hg_O contacts are indicated by dashed lines. In the crystal structure of the rare mineral poyarkovite Hg3OCl, six (Hg2)2+ pairs were found; 36 the distances between the mercury atoms vary from 2.503 to 2.565A. The (Hg2)2+ cations are located along three mutually perpendicular directions. Each oxygen atom forms four tetrahedrally directed Hg7O bonds (1.94 ¡À 2.51A) through which the mercury pairs are linked in a framework (Fig.8). The above-mentioned structure of the mineral eglestonite (Hg2)3Cl3O2H (see Ref. 37) consists of four interpenetrating cubic three-dimensional frameworks (Hg2)3O2 (see Ref. 1), in which the oxygen atoms are involved in three Hg7O bonds and link the (Hg2)2+ pairs located along each bond of the framework. a 0 Figure 8. Systems of the mutually perpendicular (Hg2)2+ pairs in the structure of poyarkovite Hg3OCl. 0 c Hg(1) Hg(3) O(6) Hg(4) Hg(2) O(3) Sb O(1) O(5) O(4) O(2) DHg, DO DHg, DCl, DOc 623 The frameworks are linked to each other through short O7H_O hydrogen bonds (O_O, 2.59A) and chlorine atoms. In the structure of magnolite Hg2TeO3, the 7O7Hg7 Hg7O7 fragments are linked via the tellurium atoms (Te7O, 1.93A) in zigzag chains extended along the [010] direction. The chains are linked through Hg_O contacts (2.692 ¡À 2.998A).There are also short O_O distances (2.817 and 2.750A).38 The study of edgarbaileyite Hg6Si2O7 demonstrated 39 that the Hg7Hg pairs in this structure are parallel to each other and the 7O7Hg7Hg7O7 fragments are virtually linear. Each mer- cury atom is additionally coordinated by two oxygen atoms (the Hg7O distances are 2.41 ¡À 2.86A). The Si2O7 groups are located between the mercury pairs and are linked in a framework through the Hg7O bonds (2.21 and 2.63A). The distinguishing feature of the structure of szymanskiite Hg16(Ni,Mg)6(CO3)12(OH)12(H3O)8 .3H2O is that the MO6 octa- hedra (M=Ni or Mg) are linked to the linear 7O7Hg7Hg7O7 fragments in a rigid framework with large channels (the diameter is 13.6A) (Fig. 9).40 The channels are occupied by the disordered CO3 groups and the water molecules, which are rather weakly bound to each other. This gives grounds to consider this mineral as a nonsilicate zeolite. Note that in the structure of szymanskiite, like in the structure of AgHg2PO4 (see Ref. 32), the mercury atoms belonging to one type of the (Hg2)2+ pairs have an umbrella-shaped coordination with the involvement of three oxygen atoms of the CO3 groups located at longer distances (Hg7O, 2.34 and 2.44A). This coordination is rarely observed in monovalent mercury compounds. 3 , Analysis of the structures of inorganic compounds containing (Hg2)2+ groups with different ligands demonstrates that the Hg7Hg distances vary from 2.45 to 2.59A.No distinct correla- tions between the Hg7Hg and Hg7X distances in the X7Hg7Hg7X groups and the nature of inorganic ligands X were observed. In the series of the compounds with the NO¡¦ BrO¡¦3 , TeO23 ¡¦ and VO¡¦3 ligands, the Hg7Hg distances increase from 2.50 to 2.54A, which can be related to a decrease in the electronegativity of the ligands in this series of anions. In the series of the compounds with the ReO¡¦4 , PO34 ¡¦ and AsO34 ¡¦ ligands, the Hg7Hg distances vary from 2.506 to 2.535A. The shortest distance was observed in the HgReO4 compound because the total negative charge of the ReO¡¦4 anion is smaller than the effective negative charge of the oxygen atom due to the higher oxidation state of the rhenium atom compared to the phosphorus and arsenic atoms.The increase in the Hg7Hg distance from 2.50A in mercury nitrate to 2.52A in mercury nitrite can also be attributed to the lower degree of oxidation of the nitrogen atom in the NO¡¦2 anion compared to that in the NO¡¦3 anion. The longest Hg7Hg distance in the three-dimensional Hg7O framework (2.56A) is observed if the coordinating oxygen atoms bind only 0 b DHg DNi DC DO a Figure 9. Fragment of the crystal structure of szymanskiite.624 (Hg2)2+ groups, i.e., a competing cation is absent. An increase in the Hg7Hg distance can also occur, apparently, due to an increase in the covalence of the Hg7X bond.5 4 A noticeable effect of a strong metal7metal bond on the configuration of compact tetrahedral SO2¡¦ 4 , SiO44¡¦, PO34 ¡¦ and AsO3¡¦ anions was observed only in some instances, for example, in the (Hg2)3(AsO4)2 compound.23 An increase in the length of one Br7O bond compared to the remaining bond lengths was also found in Hg2(BrO3)2.14 Hence, the coordination of the mercury atoms in oxygen- containing compounds is generally linear with one short Hg7O distance (*2.10A) and one-to-two additional atoms located at substantially larger distances.In the mineral szymanskiite and in phosphate AgHg2PO4, some mercury atoms in the Hg7Hg dimers are nonlinearly coordinated by the oxygen atoms [an umbrella of three oxygen atoms with the larger Hg7O distances (2.22 ¡À 2.44A)].III. Mixed-valence inorganic mercury compounds The data on a number of rather rare mixed-valence compounds containing Hg2+ cations and Hgn groups (n=2 or 3), in which the oxidation state of the mercury atoms is lower than +2, are available. The principal crystal-structural characteristics of these compounds are given in Table 1. The existence of a compound containing mercury in two oxidation states, viz., in +2 and +1, was first reported in a study,41 in which the results of X-ray diffraction study of the synthetic analogue of the rare mineral terlinguaite Hg4O2Cl2 were discussed. Several studies were devoted to the crystal structures of the natural samples and their synthetic analogues.41 ¡À 44 The studies confirmed the fact that the mercury atoms in terlinguaite exist in different oxidation states, viz., in +2 and +4/3 (in the unique triangular Hg3 clusters).Two new mercury oxohalides, viz., the bromine and iodine analogues of terlinguaite, were synthesised in the study. 45 Dark- red platelet-like crystals of Hg2OI were grown by the hydro- thermal method at 450K from a stoichiometric mixture of HgO and Hg2I2. X-Ray diffraction study of the resulting compound, whose stoichiometry is identical to that of terlinguaite, demon- strated that this compound, though also mixed-valence, has quite a different structure. The structure of Hg2OI (see Ref. 46) consists of infinite zigzag chain Hg2+7O7Hg2+ along the b axis.These chains are linked through the (Hg2)2+ pairs to form 14-membered rings, which, in turn, are linked in a three-dimensional framework through weak additional Hg2+_O bonds (2.47A) (Fig. 10). The iodine atoms occupy the cavities in the layers and form weak contacts with the Hg2+ cations. The coordination Hg2+7O bonds in the structure of Hg2OI are somewhat longer (2.13 and 2.16A) and the O7Hg2+7O angles are smaller (165 8) than the corresponding values in divalent mercury compounds.47 Appa- rently, this is attributable to the contacts of the Hg2+ cation with the oxygen atom (2.47A) and with the iodine atoms (3.05 and 3.14A). Taking into account these weak bonds, the coordination polyhedron about Hg2+ can be described as a distorted square pyramid.The mercury atoms of the (Hg2)2+ pairs are linearly coordinated by the oxygen atoms and the shortest (Hg2)2+_I distance is 3.47A. In the middle 80s, two research groups 27, 48 independently prepared and studied lemon-yellow crystals of the hydrolysis product of Hg2(NO3)2 . 2H2O, viz., the mixed-valence Hg4O2(NO3)2 compound, whose stoichiometry is identical to that of Hg2OI. These compounds are partially similar in struc- ture. In the crystal structure of Hg4O2(NO3)2, as in the structure of Hg2OI, the O7Hg2+7O chains and the (Hg2)2+ pairs also form analogous 14-membered rings. However, unlike the structure of Hg2OI, the rings in Hg4O2(NO3)2 are linked in corrugated layers parallel to the (201) plane (Fig.11) rather than in a three- dimensional framework. The Hg7Hg (2.510A) and Hg7O (2.136A) bonds within the layers are covalent and the layers are N V Pervukhina, S A Magarill, S V Borisov, G V Romanenko, N A Pal'chik 0 b a DHg, DO Figure 10. Framework of the 14-membered [7(Hg2)2�¢ 2 7O67Hg24�¢7] rings in the structure of Hg2OI. linked through the weak (Hg2)2+_O contacts (2.84A) and the NO¡¦3 ions, which act as bridging ligands for the mercury atoms. This layered structure accounts for the noticeable cleavage of the crystals of Hg4O2(NO3)2 parallel to the (201) plane. The coordi- nation numbers of the Hg2+ cation and the mercury ions in the (Hg2)2+ pair are equal to 2. It is worthy of note that the bonds between the mercury atoms of the (Hg2)2+ pair and the oxygen atoms are substantially longer than the Hg2+7O distances.In attempting to synthesise the bromine analogue of terlin- guaite, viz., Hg2OBr (see Ref. 45) (hydrothermal synthesis at 460K from a stoichiometric mixture of HgO and Hg2Br2), crystals with composition Hg8O4Br3, were obtained and studied by X-ray diffraction analysis.49 The structure of Hg8O4Br3 differs from the structures of terlinguaite Hg4O2Cl2,44 Hg2OI 46 and Hg4O2(NO3)2.27, 48 There are five independent routes by which monovalent mercury atoms form three (Hg2)2+ pairs (2.517 ¡À 2.557A) and three independent Hg2+ ions per asymmet- ric unit. The metal atoms in the (Hg2)2+ pairs have the oxygen 0 b Hg(2) OHg(1) a DHg DO DN Figure 11.Layer of the 14-membered [7(Hg2)2�¢ 2 7O67Hg24�¢7] rings in the structure of Hg4O2(NO3)2.Crystal chemistry of compounds containing mercury in low oxidation states atoms as the nearest neighbours at distances of 2.14 ¡À 2.24A through which the 12-membered [7O7(Hg2)2+7]4 rings are formed. These rings are linked in infinite chains via the (Hg2)2+ dimers (Fig. 12). The Hg2+ ions coordinated by the oxygen atoms form helical chains (the Hg2+7O distances vary from 2.01 to 2.18A) similar to those found in two modifications of HgO.50, 51 The oxygen atoms bind the `divalent' and `monovalent' portions of the structure to form a three-dimensional framework with the bromine atoms located in the cavities (the shortest Hg_Br contact is 3.02A). Hg(1) O(1) Hg(2) Hg(4) Hg(5) Hg(3) O(2) Hg(6) Hg(8) Figure 12.12-Membered [7O7(Hg2)2+7O7] rings linked through the (Hg2)2+ pairs in the structure of Hg8O4Br3. 4 In the ternary Hg7Re7O system, four compounds contain- ing formally monovalent mercury,15 viz., HgReO4, and mixed- valence Hg5Re2O10 (two modifications) and Hg2ReO5, were structurally characterised. Unlike the molecular structure of HgReO4, all three mixed-valence compounds have polymeric structures. The polycations of the fused [(Hg2)2+7O7 (Hg2+)7O]n rings of different types form puckered two-dimen- sional infinite networated by the tetrahedral ReO¡¦ anions. The structure of Hg2ReO5 (see Ref. 15) contains 14-membered rings consisting of the oxygen atoms, Hg2+ cations and (Hg2)2+ pairs, which are analogous to those found in the structure of Hg4O2(NO3)2 (see Refs 27 and 48).These rings are linked in infinite two-dimensional (but with another type of corrugation) polycationic [(Hg2)2+ . 2HgO]n networks. A comparison of two modifications of Hg5Re2O10 suggested that these compounds have related structures.52, 53 Both com- pounds contain two-dimensional infinite corrugated networks with composition [Hg2+ . 2(Hg2)2+O]n, which are separated by the tetrahedral ReO¡¦4 cations. The networks in the first modifica- tion of Hg5Re2O10 consist of fused 16-membered rings.52 The networks in the second modification contain the 10- and 22- membered rings 53 (Fig.13). Analogous networks were also found in the structure of Hg3CrO6.54 Presently, the structures of about ten mercury oxovanadates are known, among which are two compounds containing mercury in the formal oxidation state of +1, viz., HgVO3 and the mixed- valence Hg2VO4 compound.19 The architecture of the crystal structure of Hg2VO4 is very unusual, namely, the (Hg2)2+ pairs and the Hg2+ ions together with certain of the oxygen atoms form infinite helical chains, which are located on the surface of the adjacent infinite channels in such a manner that the structure projected along the short a period appears as the structure consisting of fused 14-membered rings similar to those described above in the structures of Hg2OI,46 Hg4O2(NO3)2 27, 48 and Hg2ReO5.15 The mercury ions in the (Hg2)2+ pairs and the Hg2+ cations have a normal linear coordination.The trigonal- bipyramidal VO5 groups are linked via shared edges to form infinite [(VO3)7]n chains parallel to each other and located in the centres of mercury ¡À oxygen channels. These chains have no strong bonds with mercury atoms (Hg_O>2.57A). The formula of this compound can be described as follows: [(Hg2)2+ . 2(Hg2+O)]n. .[(VO3)7]2n. 625 a DHg DO b Figure 13. Types of the Hg7O rings in the crystal structures of two modifications of Hg5Re2O10. Modification: (a) I; and (b) II. The new Hg9P5I6 compound,55 which possesses semiconduct- ing properties, contains the mercury and phosphorus atoms in different oxidation states (+2, +1 and73,72, respectively), the low-valent phosphorus atoms existing as (P2)27 dimers with the P7P distance of 2.10A.The Hg2+ ions form tetrahedra about the phosphorus atoms and octahedra, whose centres are occupied by the (P2)27 dimers. The P2Hg6 octahedra are linked via shared vertices to form layers parallel to the (100) plane. These layers are linked through the ditetrahedral P2Hg7 groups and the (Hg2)2+ pairs. In this structure, the P7Hg7P and P7Hg7Hg groups have an almost linear configuration. The coordination environ- ment about the mercury atoms is completed by the iodine atoms (the Hg7I distances vary from 3.097 to 3.691A). Taking into account the different valence states of the mercury and phospho- rus atoms, it was suggested 55 that the formula of the compound be written as (Hg7Hg)2�¢Hg2�¢ 16 (P7P)44 ¡¦P32 ¡¦I12.Presently, only a few natural mixed-valence mercury com- pounds are known. These compounds, like the rare minerals containing only (Hg2)2+ pairs, are very unstable. The X-ray structural studies of these compounds are very laborious. Recently, the crystal structures of three natural mercury chro- mates, viz., edoylerite (Hg2+)3S2CrO4 (Ref. 56), deanesmithite (Hg+)2(Hg2+)3OS2CrO4 (Ref. 57) and wattersite (Hg+)4Hg2+O2CrO4 (Ref. 58), have been studied. The last two mixed-valence compounds represent new structural types con- taining the polymeric 7O7Hg7O7 and 7O7(Hg2)2+7O7 fragments typical of mercury compounds. In the structure of sulfur-containing deanesmithite, the infinite _(Hg2)2+7 O7Hg2+7O7(Hg2)2+7[(Hg2+7S)6]7(Hg2)2+_ chains involving the 12-membered [(Hg2)2+7S]6 rings can be distin- guished. The O7(Hg2)2+7S groups are virtually linear.In wattersite (Hg+)4Hg2+O2CrO4, the CrO4 tetrahedra and the distorted Hg2+ octahedra form ribbons with composition [Hg2+CrO6]67, which are linked in slightly distorted layers parallel to the (100) plane through the (Hg2)2+ pairs. In the structure of natural mercury oxochloride, viz., in the mineral hanawaltite (Hg+)6Hg2+O3Cl2, the 7O7Hg2+7O7 and 7O7(Hg2)2+7O7 fragments form a three-dimensional framework whose cavities are occupied by the chlorine atoms.59626 The distinguishing feature of this structure is that all (Hg2)2+ pairs lie approximately in the (001) plane and form corrugated layers.The researchers attributed the planar (001) habit of the mineral to the presence of strong Hg7Hg bonds in this plane and ascribed the good cleavage in the direction perpendicular to the c axis to weak bonds, which occur between the layers along this direction through the Hg2+ ions. Another natural mercury oxochloride, viz., the above-men- tioned terlinguaite Hg4O2Cl2,44 contains alternating layers of {Hg2+Cl2} and {(Hg3)4+O2}. The latter layers contain the triangular (Hg3)4+ clusters (Hg7Hg, 2.707A), which are in a single plane (Fig. 14). The resulting structure may be represented as a three-dimensional mercury-oxygen framework with Cl atoms in the cavities. The layers containing strong Hg7Hg bonds are responsible for the anisotropy of the physical properties of hanawaltite and terlinguaite.Hg(1) a 0 Hg(3) Hg(2) b DHg DCl DO Figure 14. Crystal structure of terlinguaite Hg(Hg3)O2Cl2. 4 Only three inorganic mercury compounds, whose structures contain the triangles (Hg3)4+ in which the mercury atoms exist in the formal oxidation state of +4/3, are known. Hence, although two compounds considered below are not mixed-valence, it is reasonable to describe their structures in this section. Recently, the crystal structure of the rare hypergene mineral kuznetsovite Hg3AsO4Cl, whose structure has been previously established based on X-ray powder data,61 was refined.60 This is the second naturally occurring compound containing the cyclic (Hg3)4+ group (Hg7Hg, 2.675A).In the cubic structure, the Hg3 triangles and the AsO3¡¦ tetrahedra alternate along all crystallo- graphic axes (Fig. 15). Taking into account only short Hg7O bonds (2.17 and 2.28A), a framework can be distinguished. The cavities of this framework are occupied by the chlorine atoms in a diamond-like fashion. The third compound, viz., pale-yellow crystals of Hg9As4O16, was prepared upon thermal decomposition (550 8C) of (Hg2)3(AsO4)2.62 The crystal structure of this compound consists of the (Hg3)4+ triangles (Hg7Hg, 2.662 ¡À 2.696A) and the AsO3¡¦ 4 0 a c DHg DAs DCl DO O(1) b O(2) Figure 15. Crystal structure of kuznetsovite Hg3AsO4Cl. N V Pervukhina, S A Magarill, S V Borisov, G V Romanenko, N A Pal'chik DHg Figure 16.Arrangement of the Hg3 triangles and the AsO4 tetrahedra in the crystal structure of (Hg3)3(AsO4)4. tetrahedra and corresponds to the formula [(Hg3)4+]3[(AsO4)37]4. The coordination environment about the mercury atoms is a distorted tetrahedron with the Hg7O distances of 2.14 ¡À 2.34A. The remaining distances vary from 2.58 to 2.93A (Fig. 16). The tendency of mercury-oxygen groups to polymerisation, which is characteristic of divalent mercury compounds, is retained in compounds containing mercury atoms in different oxidation states.47 The pairs of the monovalent mercury atoms form the linear O7(Hg2)2+7O groups, which (along with the linear O7Hg2+7O units) are involved in the formation of polycations of different types, viz., rings, infinite chains, corrugated and planar networks, layers or frameworks.The triangular (Hg3)4+ group plays a similar role. Fragments containing the groups of monovalent mercury are characterised by larger deviations from linearity (the Hg7Hg7Oangles are 145 ¡À 178 8) and by elongated Hg7O bonds (2.10 ¡À 2.34A) compared to the groups containing Hg2+ (the O7Hg7O angle is 180 8; the average Hg7O distance is 2.06A). Apparently, this is due to the effect of the strmetallic Hg7Hg bond, whose length changes only slightly and is virtually independent of the coordination environment about the mercury atoms. Analysis of the bond lengths in the mixed-valence and cluster mercury derivatives demonstrates that the divalent mercury atoms are not only linearly coordinated by two atoms with the shortest distances, but also are generally surrounded by several atoms located at distances of >2.5A.When describing the structures, these atoms are often included in the coordination environment about the mercury atoms. Since the environment about the mercury atoms is often formed by atoms of different types, the spread in the distances in the polyhedra is large and the polyhedra are strongly distorted. This is also true for the environment about the monovalent mercury atoms in the (Hg2)2+ pairs and (Hg3)4+ triangles. The description of the coordination polyhedra about the individual mercury atoms becomes even more arbitrary in the presence of strong metallic bonds because these polyhedra are very distorted.n n From the crystal-chemical standpoint, it is worthwhile to consider this series of structures as structures containing the overall complex Hgx�¢ cations with the coordinates of the geo- metric centres of the complexes and to describe the coordination environment about the Hgx�¢ cation as a whole. For example, the environment about the (Hg2)2+ pair in the structure of chursinite (Hg2)3(AsO4)2 is a trigonal antiprism formed by the oxygen atoms of the AsO4 tetrahedra 23 (Fig. 17 a). In the study of the structure of kuznetsovite Hg3AsO4Cl, 61 the environment about the trian- gular mercury cluster was described as a convex 16-vertex polyhedron, viz., Friauf's polyhedron (Fig.17 b) formed by twelve oxygen atoms and four chlorine atoms. The application of this approach to other structures demonstrated that the environment about the [Hg3]4+ cation (6O+6Cl) in terlinguaite Hg(Hg3)O2Cl2 is a hexagonal analogue of cuboctahedron (Fig. 17 c)44 and the environment about the analogous cation in (Hg3)3(AsO4)4 is a cuboctahedron formed by 12 oxygen atomsCrystal chemistry of compounds containing mercury in low oxidation states abcd Figure 17. Coordination Hgn polyhedra in the structures of (Hg3)2. .(AsO4)2 (a), Hg3AsO4Cl (b), Hg(Hg3)O2Cl2 (c) and (Hg2)3(AsO4)4 (d). (Fig. 17 d).62 The symmetry and the convexity of the coordination polyhedron as well as a small spread in the distances from the centre of the mercury group to the vertices of the polyhedra and a small spread in the lenghts of the edges of the polyhedron can serve as criteria for choosing the polyhedral environment about the Hgx�¢ n cation.Note that this method would never do for describing the coordination environment about cluster mercury groups if the distances between the atoms of the adjacent mercury groups are close to the cation7anion bond lengths [for example, in the structure of poyarkovite Hg3OCl,36 in which the shortened distances (3.11 ¡À 3.13A) were observed between the mercury atoms of some adjacent (Hg2)2+ pairs]. 627 n IV. Compounds containing polyatomic Hgx�¢ cations (n>2) n Salts, which contain linear Hgx�¢ systems of metal atoms directly bound to each other (where n>2, i.e., the formal oxidation state of mercury is lower than +1) as ions, are formed in strongly acidic nonaqueous solvents and exist as stable crystalline compounds with particular anions.1 For example,63 the reactions of mercury with AsF5 and SbF5 in liquid SO2 yielded the (Hg3)2+ and (Hg4)2+ ions, which were isolated as crystalline salts with the AsF76 and Sb2F711 anions.Attempts to prepare analogous salts with other anions according to this procedure failed, apparently, due to the fact that no other pentafluorides, which can oxidise mercury in an SO2 medium at room temperature, were found. More recently, a universal procedure was developed for the preparation of compounds with the (Hg3)2+ and (Hg4)2+ cations, which involves the reaction of mercury with hexafluor- ides Hg(MF6)2.Dull-yellow crystals of Hg3(AsF6)2 and dark-red crystals of Hg4(AsF6)2 as well as analogous compounds with niobium, tantalum and antimony were prepared according to this procedure.64 The reaction of mercury and HgCl2 in a melt of AlCl3 afforded the Hg3(AlCl4)2 compound.65 It should be noted that all these salts undergo rapid disproportionation in the presence of water to form elemental mercury and (Hg2)2+ salts. The principal crystal-structural data for compounds of this type are given in Table 1. X-Ray diffraction studies of the Hg3(AsF6)2 (see Ref. 63) and Hg3(AlCl4)2 (see Ref. 66) compounds revealed the linear groups of the mercury atoms of the (Hg3)2+ type. The Hg7Hg bond lengths in these groups have equal or close values.Thus, the structure of Hg3(AlCl4)2 consists of discrete molecules with the linear central 7Cl7Hg7Hg7Hg7Cl7 skeleton (the Hg7Hg bond lengths are 2.551A and 2.562A), which involves the chlorine atoms of the tetrahedral AlCl4 groups, whereas in the structure Hg3(AsF6)2 containing the (Hg3)2+ cations and the octahedral AsF¡¦6 anions, the (Hg3)2+ cation is linear and centrosymmetrical with the Hg7Hg bond length of 2.552A (Fig. 18). The Hg_F contacts between the terminal mercury and fluorine atoms of the adjacent AsF¡¦6 anions (2.38A) are collinear with the Hg7Hg bonds. These contacts are, most likely, covalent in character because their lengths are intermediate between the reference values of 2.10 and 2.46A, respectively.63 The Hg3(NbF5)2SO4 and Hg3(TaF5)2SO4 compounds are isostructural and also contain the nearly linear centrosymmetri- cal (Hg3)2+ cations linked to the [F5MOSO2OMF5]27 anions 0 c b DHg Figure 18.Linear (Hg3)2+ cations in the crystal structure of Hg3(AsF6)2.628 (M=Nb or Ta) through the terminal oxygen atoms to form chains along the [110] and [110] directions.67 The coordination environment about the mercury atoms in the (Hg3)2+ cations is analogous to those observed in Hg3(AsF6)2 (see Ref. 63) and Hg3(AlCl4)2 (see Ref. 66). The structure of the (Hg4)2+ ion was established in the studies 6 of the crystal structures of Hg4(Ta2F11)2 (see Ref. 67) and Hg4(AsF6)2 (see Ref. 68). The terminal Hg7Hg bonds (2.630A67 and 2.620A68) in these compounds are somewhat longer than the central bonds (2.593 and 2.588A, respectively) and the bonds in the (Hg3)2+ cation.63, 66 The structures of these compounds consist of the nearly linear (Hg4)2+ cations (the Hg7Hg7Hg angles are 177.3 and 177.4 8, respectively) and the Ta2F¡11 and AsF¡6 anions, respectively.The distinguishing feature of these structures is that the distances between the adjacent (Hg4)2+ cations (3.033A67 and 2.985A68) are close to the short- est Hg7Hg distance in metallic mercury (2.99A).69 Hence, taking into account these contacts, the (Hg4)2+ cations can be considered as being linked in infinite zigzag chains (along the c axis) with weak interactions between the terminal mercury atoms (Fig. 19).Thus, the interaction between the (Hg4)2+ cation and the AsF¡ anion in the Hg4(AsF6)2 compound in the direction nearly collinear with the terminal Hg7Hg bonds may be considered as being replaced by the Hg_Hg intercationic interaction at an angle of 1248 to the terminal Hg7Hg bond [107.98 in Hg4(Ta2F11)2] and by several weak Hg_F contacts with the anions. The latter contacts are substantially longer (>2.7A) than the short inter- actions (2.38A) in Hg3(AsF6)2, which are collinear with the Hg7Hg bonds, and are similar in length to the analogous contacts in other compounds with noncollinear Hg_F interac- tions (for example, the shortest Hg_F contacts in Hg2.86AsF6 are 2.87 and 2.98A).70, 71 The reactions of mercury with AsF5, SbF5 or Hg(MF6)2 (M=Nb or Ta) on the surface of liquid mercury afforded gold- coloured crystals, which were similar in appearance to metallic crystals and existed for 10 ± 15 min.Then these crystals were converted into soluble (Hg3)2+ salts. It was possible to store and isolate these crystals by choosing a weaker oxidising agent. These crystals appeared to be the most interesting substance among the compoundsneral formula Hg37dMF6 (M=As, Sb, Nb or Ta) because they posses anisotropic metallic conductivity. The Hg37dAsF6 and Hg37dSbF6 compounds exhibit superconducting properties at low temperatures (Tc=4 and 14 K, respectively).64 The crystal structure of the unique anisotropic superconduc- tor of the empirical formula Hg3AsF6 can be described as a sublattice containing the octahedral AsF¡6 anions arranged in the tetragonal unit cell in a cubic close packing fashion.70 There are linear nonintersecting channels in two nearly perpendicular directions (parallel to the a and b axes) within this sublattice.The infinite disordered chains of the mercury atoms in the formal oxidation state of +1/3 (Hg7Hg, 2.64A) are located along these channels (Fig. 20). The unit cell parameters a=b=7.54A are not proportional to the threefold Hg7Hg distance (7.92A). 0 c b Figure 19. Linear (Hg4)2+ cations in the crystal structure of Hg4(AsF6)2. The bonds between the cations are indicated by dashed lines. N V Pervukhina, S A Magarill, S V Borisov, G V Romanenko, N A Pal'chik b 0 a c Figure 20. Infinite disordered Hgn chains in the structure of Hg37dAsF6.Hence, the empirical formula of the compound under consider- ation can be formally obtained from the ratio 7.54 : 2.64=2.86 and may be written as Hg2.86AsF6.. Neutron diffraction study of Hg3AsF6 confirmed the formula Hg2.86AsF6 and the above- described crystal structure of the compound.71 However, according to the structural data, the disordered Hgn chains are not precisely one-dimensional and the sites of the mercury atoms are only partially occupied. In addition, the maximum deviation of the mercury atoms from the axes of the chains in the [001] direction was 0.07A at room temperature and the shortest Hg7Hg contacts between the chains are 3.24A.If the chains were exactly linear, these distances would be c/4=3.098A. It was concluded 71 that the incommensurate structure is stabilised by anionic vacancies so that the unit cell contains four Hg2.86(AsF6)0.953 formula units. Hence, the structure of Hg2.86AsF6 contains the unique metal- bonded infinite polymeric cations, which form a portion of the ionic crystal lattice. The shortest contacts between the mercury and fluorine atoms (2.99A) are somewhat larger than the sum of the van der Waals radii (2.85A), i.e., the crystal structure contains the AsF76 anions and the Hgn chains, in which the average charge on the mercury atoms is equal to 1/2.86=+0.35. In this crystal, the ionic character of the bonds between the positively charged Hgn chains and the AsF76 anions predominates. In addition, it should be noted that the Hg7Hg distance (2.64A) is substantially shorter than that in metallic mercury (2.99A).However, the coordination number of Hg in metallic mercury is 12, whereas in the compound under consideration, this value is equal to 2. The character of the structure under consideration is consistent with the anisotropy of conductivity in the crystal along the a and b axes. The syntheses of a series of compounds with nonstoichiomet- ric compositions of the general formula Hg37dMF6 (M=Sb,72 Nb or Ta 73) at room temperature and of the general formula Hg37dMF6 (M=Sb or Ta 74) at 173 and 150 K, respectively, were reported. It was confirmed that these compounds are isostructural to the Hg3AsF6 compounds studied previously.70, 71 Based on the comparison of the structures of three types of the above-considered compounds and taking into account the short contacts (2.985A) between the terminal atoms of the adjacent cations (Hg4)2+, it can be concluded that the structure of Hg4(AsF6)2 is intermediate between the structure of Hg3(AsF6)2, in which short contacts between the cations are absents, and the structure of Hg37dAsF6, which contains infinite Hgn chains and in which there are no discrete cations.Taking into account the high electrical conductivity of compounds containing infinite Hgn chains, the authors 68 believed that the conductivity can occur along the zigzag chains in Hg4(AsF6)2.Crystal chemistry of compounds containing mercury in low oxidation states The preparation and investigation of gold-coloured crystals containing infinite Hgn chains with compositions Hg37dNbF6 and Hg37dTaF6 led to the unexpected discovery of a new type of mercury compounds, which contain Hgn layers, but differ from chain compounds.75 If the gold-coloured crystals were not removed from the reaction mixture containing unconsumed mercury and (Hg3)2+ and (Hg4)2+ ions in the solution, these crystals were transformed over a period of time (from several hours to several months) into thin pliable silvery plates reminis- cent of aluminium foil.The reaction performed in the cold (735 8C) afforded silvery crystals without intermediate forma- tion of gold-coloured crystals.Unlike the gold-coloured crystals, the silvery crystals have the exactly stoichiometric composition Hg3MF6 (M=Nb or Ta), which is determined by its close-packed structure. The crystals with this composition exhibit supercon- ducting properties (Tc=7 K).64 X-Ray diffraction studies of the Hg3NbF6 and Hg3TaF6 compounds revealed close-packed layers of the MF76 octahedra separated by hexagonal layers of the mercury atoms (Fig. 21).75 Each mercury atom is surrounded by six nearest neighbours at distances of 2.90A within the Hg layer and by six fluorine atoms from the adjacent MF6 layers at distances of 3.2A (three atoms from each adjacent layer). The mercury and fluorine atoms form the cubic close packing and the M atoms occupy 1/3 of the octahedral cavities between the fluorine atoms.The Hg7Hg distances in the mercury layers are longer than those in the chains, in which the mercury atoms are bound only to two neighbours, but are shorter than in elemental mercury, in which metal atoms have 10 or 12 neighbours. It should be noted that the silvery crystals were rapidly converted into the gold-coloured crystals in the presence of liquid SO2 at 120 8C. Hence, it can be stated that there is a reversible structural transition between the chain and layered structures. However, the role of SO2 in this tran- sition is not entirely known (this transition does not occur at room temperature and below room temperature in the absence of SO2). The synthesis, structure and electrical properties of salts containing polyatomic (Hg3)2+ and (Hg4)2+ cations and com- pounds with chain (Hg37dMF6, where M=As, Sb, Nb or Ta) and layered (Hg3NbF6 and Hg3TaF6) structures were considered in greatest detail in the study.64 In none of the known compounds containing (Hg2)2+ and (Hg3)2+ ions, these ions tend to bind to each other. The (Hg4)2+ ions in the compounds form zigzag chains through weak bonds. The limiting case is observed in the structures of Hg37dMF6 (d=0.1), (M=As, Sb, Nb or Ta) consisting of infinite chains, in which the oxidation state of mercury is close to +1/3 and the chains are virtually linear and uniform. The tendency of the ions to form chains, apparently, results from the low oxidation state and chains are formed if the charge on the mercury atom is lower than *+1/2.It should be noted that infinite linear chains of mercury atoms were found in b-Hg.69 The layers of mercury atoms were observed in the graphite intercalation compound with composi- a c 0b Figure 21. Hexagonal Hgn layers in the structure of Hg3NbF6. 629 tion KHgC4.76 Although the Hg7Hg distances in KHgC4 are close to those in Hg3NbF6 (2.85 and 2.90A, respectively), the layers in these structures differ in that each mercury atom in Hg3NbF6 has 6 neighbours and the formal charge of +1/3, whereas each mercury atom in the intercalation compound has only three neighbours and the formal charge of 0. 6 n n n Therefore, analysis of the structures of mercury compounds with fluorine and MF7 anions shows the strict relationship between the value of the averaged formal charge on the mercury atom, the shortest Hg7F distances, the structure of the Hgxá cation and the Hg7Hg distance in this cation.As the charge on the mercury atom decreases from+1to +1/3, the shortest Hg7F distances increase from 2.133 in Hg2F2 to 3.2A in Hg3NbF6 and the sizes of the Hgxá cation increase going from the finite and virtually linear Hg2á groups (n=2 ± 4) to the infinite Hgn chains and then to a two-dimensional close-packed layer of the mercury atoms. The Hg7Hg distances in this series of the cations increase from 2.51 to 2.90A. V. Monovalent mercury compounds with organic ligands Presently, 30 complex compounds with organic ligands containing (Hg2)2+ groups have been synthesised and structurally charac- terised. The principal crystallographic and crystal-chemical char- acteristics of these compounds are given in Table 1.Most organic ligands, which are constituents of the complexes under consid- eration, are shown in Fig. 22. Many amines, including pyridine, cause disproportionation of the dimeric (Hg2)2+ cation Hg2++Hg0. (Hg2)2+ N N N N N L4 L3 Cl CN L1 O L2 O O N N O O +N N N O7 CH2Ph NH2 L5 L7 L8 L6 Me CN O N N N N N CN Me L9 O NH2 NH2 Me L12 L10 L11 NO2 SO¡ SO¡ 3 3 +NH S S NH2 SO¡3 S7 NH2 L13 L14 L17 L15 L16 Me O F F O Me Me F O7 O7 O7 O Me Me F Me O F L20 L19 L18 Figure 22.Types of organic ligands in monovalent mercury complexes.630 The possibility of formation of stable monovalent mercury complexes with low-basicity nitrogen bases was confirmed for the first time by the detection of the (Hg2)2+ complex with aniline in solution.77 Apparently, the introduction of an acceptor sub- stituent at position 4 of the pyridine ring leads to a decrease in the donor ability of the nitrogen atom. Some substituted low-basicity pyridines and anilines also form stable [Hg2L2]X2, complexes,78 the basicity of the ligand depending on both the electronic and steric properties of the substituents. Structural study of the isolated [Hg2(L1)2](ClO4)2 compound 79 demonstrated that the (Hg2)2+ ion can be covalently coordinated to the N-donor ligands through both mercury atoms. The virtually linear N7Hg7Hg7N fragments (the Hg7 Hg7N angles vary from 162.8 to 1808) were found in dimercury perchlorates with low-basicity N-containing organic ligands of the general formula [Hg2Ln](ClO4)2 (n=2);79 ¡À 83 the Hg7Hg and Hg7N bond lengths are in the ranges of 2.487 ¡À 2.518 and 2.03 ¡À 2.22A, respectively.The structures of the complexes con- tain the dimeric [Hg2L2]2+ cations and the ClO¡¦4 anions. Note- worthy is the existence of nonbonded contacts between the mercury atoms of the (Hg2)2+ ions and the oxygen atoms of the ClO¡¦4 anions. The lengths of these contacts (2.93 ¡À 3.13A) are somewhat larger than the sum of the van der Waals radii of the mercury and oxygen atoms (2.90A).The shorter Hg_O contacts were observed in the [Hg2(L2)2](ClO4)2 (2.71A),80 [Hg2(L3)2]. .(ClO4)2 (2.79A) 81 and [Hg2(L5)2](ClO4)2 (2.77A) 83 com- pounds. In the complex with acridine [Hg2(L4)2](ClO4)2, the lengths of these contacts are 2.96A,82 and hence one can say that only weak electrostatic interactions occur between the cations and the anions. The short Hg7N distance in the complexes with the ratio (Hg2)2+ :L=1 : 2 was found in [Hg2 (L3)2](ClO4)2.81 The Hg7Hg distance (2.518A) in this compound is somewhat large- r than those in the [Hg2(L1)2](ClO4)2 (2.498A) 79 and [Hg2(L2)2](ClO4)2 (2.487A) 80 complexes. The arrangement of the [(Hg2)2+(L1)2] cations in the structure of the complex, which is analogous to the arrangement of the molecules in Hg2(NO3)2 .2H2O, is the so-called herringbone packing (see Fig. 2).7, 8 In the remaining complexes, the linear N7Hg7Hg7N fragments are primarily located parallel to one of the crystallographic axes.80 ¡À 83 4 In the [Hg2(L6)2](ClO4)2 complex 84 with the stoichiometry (Hg2)2+ : L6=1 : 2, the ligand is coordinated to the mercury atoms of the (Hg2)2+ pair through the nitrogen and oxygen atoms, the coordination environment about the mercury atoms being different. The environment about the Hg(1) atom is formed by the adjacent mercury atom (Hg7Hg, 2.506A), the nitrogen atom (2.20A) and two oxygen atoms (2.63 and 2.69A). The coordination about the Hg(2) atom involves the mercury, nitro- gen (2.20A) and oxygen (2.66A) atoms.The remaining Hg_O(L6) distances are in the range of 2.89 ¡À 4.15A. The ClO¡¦ anions are not coordinated to the metal atoms. 4 The coordination number of 3 is typical of the mercury atoms in the structures of the Hg2L4(ClO4)2 compounds. Thus, the dimercury perchlorate complex with 4-benzylpyridine (L7) con- sists of the centrosymmetrical [Hg2(L7)4]2+ cations and the ClO¡¦ anions, which are linked via weak Hg_O contacts (2.899 and 3.026A).85 Without considering these contacts, the coordination about the mercury atoms is intermediate between planar-trigonal and the so-called T-shaped 86 (one of the Hg7Hg7N angles is close to 180 8; Hg7Hg is 2.508A, Hg7N are 2.227 and 2.476A) (Fig. 23). It should be noted that the L7 ligand possesses the highest basicity in the series of the above-mentioned N-donor ligands, which is manifested in the distortion of the T-shaped environment towards the planar-trigonal coordination.A com- parison of the structural data on the dimercury complexes with sterically unhindered ligands, such as 4-cyanopyridine (L1),79 3-chloropyridine (L2) 80 and 4-benzylpyridine (L7),85 revealed an interesting correlation between the stereochemistry and the basicity of the ligands (pKa is 1.86, 2.81 and 5.59, respectively). 85 There are weak contacts between the mercury atoms and the N V Pervukhina, S A Magarill, S V Borisov, G V Romanenko, N A Pal'chik O(1) O(4) Cl(1) O(3) Hg(1) N(1) O(2) DHg DCl DN DC DO N(2) Figure 23.Molecular structure of [Hg2(L7)4](ClO4)2. oxygen atoms of the ClO¡¦4 anions in all three complexes regardless of the initial coordination of ligands in the axial positions with respect to the (Hg2)2+ pair. As the basicity of the above- mentioned ligands increases, the secondary coordination becomes more essential. In particular, the secondary Hg_L contacts [2.86A (O), 2.77A (O) and 2.476A (N)] become shorter and the Hg7Hg7L angles increase (100 8, 109 8 and 118.4 8), due to which the second ligand approaches the strong acceptor axial centre of the (Hg2L2)2+ dimer. Correspondingly, the coordination is weakened, which is manifested in the increase in the Hg7N bond length (2.16, 2.21 and 2.23A). The deviation of the N7Hg7Hg7N fragment from linearity also increases (the N7Hg7Hg angles are 176.0 8, 167.4 8 are 153.9 8).Hence, it is evident that the deviation of theN7Hg7Hg7Nfragments from linearity in stable dimercury complexes with N-donor ligands of the [Hg2Ln]2X2 type (n>2) is caused by the additional coordina- tion of the metal atoms by more remote ligands. 4 The coordination polyhedra about the mercury atoms in the [Hg2(L8)4](ClO4)2 compound are distorted tetrahedra formed by the mercury atom (Hg7Hg, 2.522A) and three oxygen atoms of the ligands (Hg7O, 2.197 ¡À 2.558A).87 An analogous coordina- tion with the elongated Hg7O bonds, which is untypical of mercury atoms, was also found in Hg2AgPO4 (see Ref. 32) and in the mineral szymanskiite.40 The remaining Hg_O contacts are longer than 2.78A.The [Hg2(L8)4]2+ dimers lie in the (010) plane. The distances between the adjacent dimers are 3.90 and 4.17A�º (Fig. 24). In addition, there is a rather long contact (2.96A) between the mercury atom and the oxygen atom of the ClO¡¦ anion. Therefore, the structure of the [Hg2(L7)4](ClO4)2 complex contains only discrete cations with the three-coordinate mercury 0 b Hg(2) Hg(1) a DCl DHg, DO, DN, DC, Figure 24. Projection of the structure of [Hg2(L8)4](ClO4)2 onto the (001) plane.Crystal chemistry of compounds containing mercury in low oxidation states atoms, whereas three of four ligands in the [Hg2(L8)4](ClO4)2 complex act as bridges between the adjacent (Hg2)2+ cations.85 The compound Hg2(Ph2Se)4(ClO4)2 exists in two forms, viz., in the `yellow' 88 and `red' 89 forms.The `yellow' complex contains the centrosymmetrical [(Ph2Se)2Hg2(Ph2Se)2]2+ cations with positively charged trivalent selenium atoms.88 One of the oxygen atoms of each ClO¡¦4 anion is bound to the (Hg2)2+ group. Each mercury atom hathe trigonal environment formed by the mercury atom (Hg7Hg, 2.558A), the selenium atom (Hg7Se, 2.70A) and the oxygen atom of the ClO¡¦4 anion (Hg7O, 2.705A). In addition, there is a contact between the mercury atom and the selenium atom (2.80A), which completes the coordination about the mercury atom to a distorted tetrahedron. The observed Hg7Hg distance belongs to the longest distances found in the (Hg2)2+ groups. The value of one of the Hg7Hg7Se angles (1418) indicates that the linear coordination about the mercury atom is distorted upon addition of the second diphenyl selenide group.Correspondingly, the Hg7Se distance is 2.70A at the Hg7Hg7Se angle of 141 8, while this distance increases to 2.80A at the angle of 1168. In the centrosymmetrical molecule of the `red' form, the central Hg2Se4 fragment is planar.89 The fourth coordination site at the mercury atom is occupied by an oxygen atom of the ClO¡¦4 anion (Hg7Hg, 2.554A; Hg7Se, 2.653 and 2.918A; Hg7O, 2.626A; the Hg7Hg7Se angle is 151.9 8). Therefore, the `yellow' and `red' forms of the Hg2(Ph2Se)4. .(ClO4)2 compound are characterised by the different structures of the Hg2Se4 fragments and the different molecular packings in the crystals.In the Hg2[(Ph3PO)6](ClO4)2 complex with the stoichiometry (Hg2)2+:L=1 : 6, the coordination environment around each mercury atom is a tetrahedron formed by three ligands and the adjacent mercury atom of the (Hg2)2+ pair. As a result, the discrete complex cation is formed (Hg7Hg, 2.522A; Hg7O, 2.29 ¡À 2.43A).90 The ClO¡¦4 anions are not involved in the coordi- nation sphere about the mercury atoms. In this complex, the mercury atoms have the so-called umbrella-type coordination for- med by the oxygen atoms of the ligands with elongated Hg7O bonds. This coordination is analogous to that found in Hg2Ag. .PO4,32 szymanskiite 40 and the [Hg2(L8)4](ClO¡¦4 )2 complex.87 It should be noted that compounds of the Hg2L2X2 type contain discrete dimeric cations, in which each mercury atom is linearly coordinated.The Hg7L bonds are in the range of 2.03 ¡À 2.35A and the X anions are located at large distances from the mercury atoms (2.8 ¡À 3.0A). In the compounds with compo- sition Hg2L4X2, the coordination about the mercury atoms is intermediate between linear and tetrahedral. Besides, data on polymeric complexes with bridging N-containing L ligands, which are analogous to those found in [Hg2(L8)4](ClO4)2 with O-containing ligands, are lacking.87 Only in the Hg2[(Ph3PO)6]. .(ClO4)2 compound, is the coordination environment about the mercury atoms a tetrahedron.90 The existence of the stable mercury complex with 1,10- phenanthroline (Phen) confirms the possibility of complexation of dimercury ions with low-basicity amines.The Hg2Phen(NO3)2 complex with the ratio (Hg2)2+:L=1 : 1 has a layered structure. The discrete [Hg2(Phen)]2+ cations are separated by layers of the NO¡¦3 anions.91 The mercury atoms have different coordinations. Thus, the Hg(1) atom has four nearest neighbours; the tetrahe- dron is formed by the Hg(2) atom (Hg7Hg, 2.516A), the nitrogen atoms of the phenanthroline molecule (2.30 and 2.48A) and the oxygen atom of NO¡¦3 anion (2.59A). Another oxygen atom of the NO¡¦3 anion is located at a distance of 2.91A. The nearest environment about the Hg(2) atom is formed by the Hg(1) atom and the oxygen atom of the NO¡¦3 anion. The remaining oxygen atoms are at distances of 2.75 ¡À 2.95A.Therefore, the 1,10- phenanthroline molecule is bound to only one mercury atom of the (Hg2)2+ pair. Attempts to isolate the compound with composition Hg2(Phen)2(NO3)2 failed. In compounds with the stoichiometry Hg2�¢ 2 : L=1:2 [Hg2(L9)2](NO3)2 and [Hg2(L10)2](NO3)2, the nearly linear 631 7N7Hg7Hg7N7 groups were found with the Hg7Hg distances of 2.551 92 and 2.517A93 and the Hg7N distances of 2.168A92 and 2.193A.93 The shortest distances to the oxygen atoms of the NO¡¦3 anions are 2.696 ¡À 3.000A. The authors 93 believed that the contacts, characterised by these lengths, play a decisive role in the molecular packing of the complex. The structures of [Hg2(L11)2](NO3)2 (see Ref. 94) and [Hg2(L12)2](NO3)2 (see Ref.95) contain the nearly linear 7N7Hg7Hg7N7 groups (Hg7Hg, 2.518A94 and 2.524A95; and Hg7N, 2.233A94 and 2.209A95). Taking into account the Hg_O distance (2.659A), the coordination about the mercury atoms is close to T-shaped.94 In addition, each mercury atom has contacts with the oxygen atom of the NO¡¦3 anion (Hg_O, 2.769A) and the nitrogen atom of the nitrile group (2.906A). The NO¡¦3 anions are involved in hydrogen bonding with the NH2 groups of the adjacent molecules (N_O, 2.88 and 3.02A) through the noncoordinated and coordinated oxygen atoms to form chains along the [100] direction. These chains are linked in layers parallel to the (010) plane through the Hg7NCN interactions (2.906A). 3 The mercury atoms in the dimeric cation of the Hg2(L13)2(NO3)2 complex have different coordinations. Thus, the Hg(1) atom is coordinated to the Hg(2) atom at a distance of 2.541A and, in addition, forms a covalent bond with the sulfur atom of the ligand (2.49A).The S7Hg7Hg7S fragment is virtually linear (the Hg7Hg7S angle is 173.5 8).96 The coordina- tion environment about the Hg(2) atom is more complicated. The nearest environment involves the oxygen atoms of two NO¡¦ groups (2.516 and 2.651A) along with the sulfur atom of the ligand (2.584A). In addition, there are Hg_O contacts between the Hg(1) atom and the NO¡¦3 groups (2.773 and 2.820A). The L13 ligands serve as bridges between the mercury pairs. In the structure, the7L137(Hg2)2+7L137chains are extended paral- lel to the [101] direction.contains compound the Hg2(L14)2(NO3)2 3The [7(Hg2)2+7S7(Hg2)2+7] chains with the three-coordinate sulfur atoms and the NO¡¦3 anions (Hg7Hg, 2.548A; Hg7S, 2.488 and 2.477A; the Hg7Hg7S angles are 161.9 and 163.88);97 Hg_Ocontacts (2.64 ¡À 3.14A) are observed. The O(3) atom of the NO¡¦ anion acts as a bridge [Hg(1)7O(3), 2.652A�º ; and Hg(2)7O(3), 2.636A], completes the coordination about the mercury atom to T-shaped and links the chains in corrugated ribbons along the b axis (Fig. 25). In the crystal of the complex Hg2(L15)2(H2O)2, the molecules exist as zwitter-ions with the formal positive charge on the nitrogen atom and the negative charge on the sulfate ion.98 The N7Hg7Hg7N fragment has a nearly linear configuration.The 0 b Hg(1) S(1) Hg(2) O(3) a DHg, DO, DS, DN Figure 25. Corrugated ribbons extended along the b axis in the crystal structure of Hg(L14)2(NO3)2.632 Hg7Hg bond is rather short (2.494A). The mercury atoms form additional contacts with the oxygen atoms of the water molecules (2.621A) and of the SO¡¦ 3 3 groups of the L15 ligand (2.680A). The structures of Hg2(L16)2, Hg2(L17)2 and Hg2(L17)2(H2O)2 contain the centrosymmetrical complexes, in which the mercury atoms are coordinated by the nitrogen atoms to form the nearly linear [7N7Hg7Hg7N7] fragments.99 The Hg7Hg bond lengths are 2.500, 2.515 and 2.522A in Hg2(L16)2, Hg2(L17)2 and Hg2(L17)2(H2O)2, respectively. The Hg7N bond lengths are virtually identical (the average value is 2.19A).In the Hg2(L16)2 and Hg2(L17)2(H2O)2 compounds, the (Hg2)2+ pairs are rotated with respect to each other by 78 and 68 8, respectively. In Hg2(L17)2, these pairs are parallel to each other. There are weak Hg_O interactions, whose lengths are close to the sum of the van der Walls radii. Thus, there are contacts with three oxygen atoms of two ligand molecules (2.67, 2.92 and 2.99A) in the Hg2(L16)2 compound, contacts with the oxygen atoms of the SO2¡¦ group (2.68A) in Hg2(L17)2 and contacts with the oxygen atoms of the ligand (2.711A) and of the water molecule (2.715A) in Hg2(L17)2(H2O),. The Hg2(L16)2 and Hg2(L17)2(H2O)2 complexes are linked in layers and the Hg2(L17)2 complexes are linked in chains through the ligand molecules .26). In the Hg2(L17)2 and Hg2(L16)2 compounds, the oxygen atoms of the SO2¡¦ 3 groups are involved in intermolecular hydrogen bonding with the NH2 groups (N_O, 2.85 ¡À 3.06A). In Hg2(L17)2(H2O)2, the oxygen atoms are involved in hydrogen bonding with the water molecules (O_O, 2.777 and 2.784A). The nearest environment about each mercury atom of o-phthalate Hg2(L18)2 involves the oxygen atom. In this case, the virtually linear O7Hg7Hg7O fragments are formed (Hg7Hg, 2.519A; and Hg7O, 2.16 and 2.08A). The (Hg2)2+ pairs link the o-phthalate groups to form infinite zigzag chains.100 In the unit cell, eight crystallographically equivalent chains are linked in pairs and are located parallel to the b axis, i.e., along the longest crystallographic axis.The typical pseudosymmetrical dimer with the Hg7Hg bond (2.514A) was also found in the [Hg2(L19)2]n compound.101 The L 19 ligand is involved in one strong bond (Hg7O, 2.13A) and one weak intermolecular Hg_O bond (2.63A) through which the (Hg2)2+ dimers are linked in chains along the [100] direction. Taking into account this bond, the coordination about the mercury atom is close to T-shaped. The crystal structure of Hg2(CF3CO2)2 consists of discrete Hg2L2 molecules. The [7O7Hg7Hg7O7] fragments are virtually linear (Hg7Hg, 2.505A; and Hg7O, 2.14A).102 The additional Hg_O distances (2.81 and 2.88A) have no substantial effect on the characteristic coordination about the mercury atom.The Hg2(CF3CO2)2 molecules are linked in corrugated ribbons along the [001] direction through intermolecular Hg_O bonds (2.64A) (Fig. 27). Taking into account this contact, the coordina- tion about the mercury atom is T-shaped. In the crystal structure, the ribbons are linked in layers via F_F contacts (2.78 ¡À 3.12A). In the Hg2[C(CN)3]2 complex,103 the (Hg2)2+ ions form three elongated bonds with the nitrogen atoms of the CN7 groups (Hg7N, 2.287 ¡À 2.508A) along with the Hg7Hg bond (2.506A). This coordination is analogous to the coordination about the mercury atoms of the (Hg2)2+ pairs mentioned in several studies.32, 40, 87, 90 The centres of the (Hg2)2+ pairs coincide with the inversion centres. The ligands are bridging and tridentate.All the nitrogen atoms of each ligand are involved in coordination about different mercury atoms to form a three-dimensional framework (Fig. 28). In the centrosymmetrical cation of the Hg2(C7HN4)2 complex, the mercury atoms have the distorted trigonal environment formed by the adjacent mercury atom and the nitrogen atoms of two carbanions of the ligand (Hg7Hg, 2.503A; Hg7N, 2.207 and 2.560A; the Hg7Hg7Nangles are 162.2 and 116.5 8).104 The cations are linked in chains along the a axis through the ligands. The mercury atoms form weak Hg_N contacts (2.753 and 2.935A) through which the chains are linked in layers (Fig. 29). N V Pervukhina, S A Magarill, S V Borisov, G V Romanenko, N A Pal'chik * a * * * * * * * S(1) O(3) O(2) 0 b O(1) HgN(1) a * * * * * * * *b 0 b Hg N(1) O(1) O(2) S(1)O(3) a * c * * * 0 b O(2) Hg O(1) N(1) O(3) S(1) a * * * * DHg, DS, DO, DN Figure 26.Molecular packings in the structures of the complexes: (a) Hg2(L16)2; (b) Hg2(L17)2(H2O)2; and (c) Hg(L17)2. The rather unusual complex with hexamethylbenzene with composition [Hg2(L20)6](AlCl4)2 .C7H8 was described. 105 The hexamethylbenzene L20 ligands are asymmetrically coordinated to the (Hg2)2+ dimer in the Z2 fashion. The distances from the mercury atoms to the planes of the ligands are 2.356 and 2.367A. In the crystal structure, the complexes with the Hg7Hg bondsCrystal chemistry of compounds containing mercury in low oxidation states a O(1)O(2) Hg 0 DHg, DO, DF Figure 27. Crystal structure of Hg2(CF3CO2)2.The F_F contacts are indicated by dashed lines. 0Hg(2) N(2) N(6) N(1) N(5) N(3) Hg(1) N(4) b DHg, DN, DC Figure 28. Projection of the crystal structure of Hg2[C(CN)3]2 onto the (100) plane. a N(1) N(2) Hg(2) N(3) Hg(1) 0 DHg DN Figure 29. Layered structure of the Hg2(C7HN4)2 complex. 633 (2.515A) are located parallel to the b axis. The structure contains also distorted AlCl4 tetrahedra. The shortest Hg_Cl distances are 3.10 and 3.12A. c c Analysis of the Hg7Hg and Hg7L bonds in the monovalent mercury complexes with organic ligands demonstrates that there is no strict correlation between these parameters, as in inorganic compounds containing mercury in low oxidation states. The Hg7Hg distances vary from 2.487 to 2.558A, which is in good agreement with the distances observed in the crystal structures of inorganic compounds. In the complexes of the Hg2LnX2 type (n=2, 4 or 6) with X=ClO¡¦4 (see Refs 79 ¡À 90), the anions have no substantial effect on the Hg7Hg bond length and are involved only in nonbonded interactions with the metal atoms, whereas the oxygen atoms of the anions in the complexes with X=NO¡¦3 (see Refs 91 ¡À 97) complete the coordination about the mercury atoms of the (Hg2)2+ pairs (Hg_O, 2.516 ¡À 2.769A).In the Hg2(L15)2(H2O)2 (see Ref. 98) and Hg2(L17)2(H2O)2 (see Ref. 99) complexes, the water molecules are involved only in formation of additional bonds with the mercury atoms of the (Hg2)2+ pairs or in hydrogen bonding with the atoms of the ligands, whereas inorganic aqua complexes contain the aqua [H2O7Hg7Hg7OH2]2+ cations.In the molecular complexes of the Hg2L2 type, the Hg7Hg bond lengths vary from 2.500 to 2.519A.99 ¡À 104 The complexes are linked in chains and layers through additional Hg_L contacts, as in inorganic monovalent mercury compounds. The coordination environment about the mercury atoms is formed primarily by atoms of organic ligands. In most compounds, anions are not coordinated to the metal atoms (the coordination number of the mercury atoms is 2).79 ¡À 83 When the coordination number of Hg increases to 3 or 4 taking into account the contacts with the anions, the structures can be described as chain, layered 9 and framework.4 ¡À 102, 104, 105 VI.Mercury-containing transition metal clusters Presently, the data on a series of mercury-containing transition metal clusters containing either (Hg2)2+ pairs or more compli- cated cluster Hgn groups are available. The principal crystallo- graphic and crystal-chemical data for selected mercury-containing clusters are given in Table 1. In this section, we consider the mercury-containing clusters with the Hg7Hg bond lengths varying in the range of 2.65 ¡À 3.27A. The structure of the Hg2Co2[N(CH2CH2PPh2)3]2(THF) clus- ter consists of the discrete {[N(CH2CH2PPh2)3]Co(Hg7 Hg)Co[N(CH2CH2PPh2)3]} molecules and the tetrahydrofuran molecules located between the complex molecules.Two Co[N(CH2CH2PPh2)3] fragments are linearly bonded through the (Hg2)2+ ion (Fig. 30) so that the four metal atoms of the 7Co7Hg7Hg7Co7fragment are coplanar (the Co7Hg7Hg angles are 179.7 and 178.4 8).106 The two-coordinate mercury atoms are shielded from additional bonding with the Ph rings of the [N(CH2CH2PPh2)3] ligands. The Hg7Hg distance (2.651A) is somewhat larger than those in the dimercury complexes with organic ligands. The shortest contact between the carbon atoms of the Ph rings and the mercury atoms is 3.48A. The study of the compound {Hg2Pt6[Ph2P(CH2)6PPh2]3. c .(C8H9NC)6} . 2C6H6 demonstrated that the (Hg2)2+ pair is inserted into the trigonal antiprismatic cage of the platinum atoms.107 Two Pt3 triangles are tightened by three [Ph2P(CH2)6PPh2] ligands.Six isocyanide molecules act as bridg- ing ligands in each triangular unit. The Hg7Hg distance (2.872A) is larger than the analogous distances in monovalent mercury compounds with organic ligands but is somewhat shorter than the distances between the metal atoms in metallic mercury.69 The structural studies of mercury-containing metal carbonyl compounds demonstrated that, as in compounds containing linear Hgn chains (n=3 or 4), the Hg7Hg distances are in the range of 2.5 ¡À 2.8A. This is indicative of a strong covalent bond, which is formed due to the overlap of the linear sp-hybridised orbitals. In the cases where other atoms, for example, transition634 a Ph2P PPh2 Hg Co Hg N Co PPh2 Ph2 Ph2PPh2P P c NEt2 S S Hg S Cp Hg Nb Et2N Cp S HgS S NEt2 e Hg Rh Rh Hg Hg Hg Hg Rh Hg Rh Figure 30.Schemes of the structures of mercury-containing transition metal clusters: (a) Hg2 Co2[N(CH2CH2PPh2)3]2(THF); (b) {Hg3[(Ph2P)2CH2]3}(SO4)2 .1.5H2O; (c) [Nb(Z-C5H5)2{HgS2CN. .(C2H5)2}3]; (d) [(Z5-CH3C5H4)Mn(CO)2Hg]4; (e) [(C12H36)3Rh]4Hg6; and (f) [Hg9Co6(CO)18] . 2(C3H6O). metals (M), are involved in the Hg7Hg bond, the distances in the clusters increase to 3.2A. In the [(Ph3P)2N]2[Hg2Os18(CO)42C2] cluster, the vertices of the Os triangles are linked through the mercury atoms to form the Os9C(CO)21 units.108 The molecule is centrosymmetrical with respect to the midpoint of the Hg7Hg bond. The Hg7Hg distance is 2.744A, whereas the Hg7Hg bond in the [(Ph3P)2N]4[Hg2 (Os18(CO)42C2](CH2CH2) cluster,109 which con- tains the framework of the metal atoms with a similar structure, is somewhat longer (2.820A).4 The triangular (Hg3)4+ cluster containing the mercury atoms in the oxidation state of +4/3 was found in the {Hg3[(Ph2P)2CH2]3}(SO4)2 . 1.5H2O compound. 110 Each mer- cury atom is bound to the bridging (Ph2P)2CH2 ligands. In addition, two SO2¡ anions form weak contacts with the mercury atoms. The Hg7Hg distances are 2.763, 2.764 and 2.802A, which are comparable with the analogous distances in the triangular groups observed in terlinguaite,44 kuznetsovite 60 and Hg9As4O16.62 In the [(Ph3P)2N]2[Ru18Hg3(C)2(CO)42] .CH2Cl2 cluster, the mercury triangle links two tricapped octahedral [Ru9(CO)21C] (Hg7Hg, 2.922A; fragments Hg7Ru, 2.919 and 2.640 ± 2.734A).111 It should be noted that the Hg7Hg distances are virtually equal to the corresponding distances in metallic mercury.69 In the solid state, the [Ru18Hg3(C)2(CO)42]27 dianion has the symmetry C3.The average angle of rotation of the central Hg3 triangle with respect to the two adjacent Ru3 triangles is 30 8. The short Hg_CCO contacts (the average length is 2.64A) are present in the structure. An analogous Hg3 unit links two [Os9(CO)21C] fragments in the [(Ph3P)2N]2[Hg3Os18(CO)42C2] .CH2Cl2 cluster, the mercury triangle (Hg7Hg, 2.919 ± 2.931A) being disordered.112 Note that the Cd3 triangle with the average Cd7Cd bond length of 2.980A b Ph2P PPh2 Hg N Ph2P PPh2 Hg Hg PPh2 Ph2P d CO MeC5H4 CO C5H4Me Mn Hg MnCO OCHg OC HgCO Mn Hg C5H4Me Mn MeC5H4 CO CO f Co Hg Hg Co Co HgHg Hg Hg Co Hg Hg Hg Co Co N V Pervukhina, S A Magarill, S V Borisov, G V Romanenko, N A Pal'chik was found in the structurally related [m3-Co(CO)3]Cd3{m- [(CO)9Co3(m3-CCO2)]}3(THF)3 cluster.113 A series of Hg-containing metal clusters containing the heteronuclear triangular MHg2 fragment were studied.The Hg2Ag[(Ph2P)2CH2]3(CF3SO3)3 cluster contains the Hg2Ag tri- angle all vertices of which are bound to the [(Ph2P)2CH2] bridging ligands.114 The Hg7Hg (2.660A) and Hg7Ag (2.805 and 2.853A) distances are close to those found in AgHg2PO4.32 The mercury and silver atoms have an approximately planar-square coordination formed by two metal atoms and two phosphorus atoms.In the examples of mercury-containing transition metal clusters considered below, the Hg7Hg bonds (2.883 ± 3.274A) approximate the distances in metallic mercury. Therefore, the mercury7transition metal bonds in these clusters prevail. The rather unusual nearly planar Hg3Nb unit, which is located in the equatorial plane of the wedge-shaped Cp2Nb sandwich, was found in the organometallic [Nb(Z-C5H5)2{HgS2CN(C2H5)2]3 cluster.115 The dihedral angle between the NbHg(1)Hg(2) and NbHg(2)Hg(3) triangles in this complex is *5 8. The Hg7Hg bond lengths (2.883 and 2.901A) are indicative of a rather strong interaction between the adjacent mercury atoms.The Hg7Nb distances vary from 2.777 to 2.808A. The cluster molecules are linked in dimeric units through the weak Hg_S bonds [Hg(2)7S(11), 3.39A]. The organometallic [(Z5-CH3C5H4)Mn(CO)2Hg]4 com- pound 116 contains the eight-membered Mn4Hg4 metallocycle in which four mercury atoms form a planar square with the Hg7Hg distances of 2.888A. The four-membered virtually planar Hg4 ring (the Hg7Hg7Hg bond angle is 90 8) was also found in the [(Z5-C5H5Re(CO)2Hg]4 cluster with an analogous structure.117 The rhenium atoms are alternately located above and below the plane of the mercury square. The average angle of bend of the angular HgReHg fragments is 19.0 8.The slight shortening of the Hg7Hg bonds (2.92A) compared to the distances in metallic mercury (2.99A) is indicative of the metal7metal interaction in the Hg4 ring of the cluster. The authors believed that the distortion of the linear coordination of the mercury atoms (the Re7Hg7Re angle is 158.8 8) is also evidence in favour of the Hg7Hg interaction. The observed eight-membered ring system is similar to that found previously in [(Z5-CH3C5H4)Mn(CO)2Hg]4..116 It should be noted that the Hg7M bonds are substantially shorter than the Hg7Hg distances in the above-described compounds [2.64A (Mn) and 2.74A (Re)]. The octahedra of six mercury atoms were observed in two clusters, viz., in [(C12H36)3Rh]4Hg6 (see Ref. 118) and [(C8H18P)2Pt]4Hg6 (see Ref.119). In the molecular structures of both compounds, the Rh and Pt atoms act as `caps,' which complete the faces of the Hg6 octahedra to form the heteroatomic Hg6M4 tetrahedron. The Hg7Hg bond lengths in the nearly regular mercury octahedra are in the ranges of 3.129 ± 3.149 118 and 3.081 ± 3.274A.119 The Hg7Rh and Hg7Pt distances are in the ranges of 2.690 ± 2.724 and 2.671 ± 2.876A, respectively. In the [Hg9Co6(CO)18] . 2(C3H6O) cluster, 120 the structural unit containing nine mercury atoms was found. The framework of the metal atoms can be described as a distorted Co6Hg9 trigonal prism with the cobalt atoms occupying all vertices and the mercury atoms being located in the midpoints of the edges. The distances between the mercury atoms located in the centres of the triangular bases of the prism vary from 3.065 to 3.138A, whereas the distances from these atoms to the mercury atoms located in the midpoints of the edges of the prism, which link two bases, are somewhat longer (3.086 ± 3.198A).The authors 120 believed that the Hg7Co interaction (2.521 ± 2.609A) is the governing factor in the formation of the framework of the metal atoms. The nature of the Hg7Hg interactions in the clusters of this type is still unclear. In the review, 121 the structures of transition metal clusters with mercury atoms were considered and an attempt was made to explain the nature of the Hg7Hg and Hg7M bonds. The structural studies of transition metal clustersCrystal chemistry of compounds containing mercury in low oxidation states revealed the existence of the linear M7Hg7M units containing two-coordinate mercury atoms. The clusters can be divided into two types, viz., two-dimensional clusters in which mercury atoms form polygons {for example, a triangle in (C36H30NP2)2. .[Hg3Os9(CO)21C2] .CH2Cl2 (see Ref.112) or a square in [(Z5- CH3C5H4)Mn(CO)2Hg]4 (see Ref. 116)}, and three-dimensional clusters in which mercury atoms form polyhedra {for example, an octahedron in [(C12H36)3Rh]4Hg6 (see Ref. 118) and [(C8H18P)2Pt]4Hg6 (see Ref. 119) or a tricapped trigonal prism in [Hg9Co6(CO)18] . 2(C3H6O) (see Ref. 120)}. The mercury atoms in these clusters are characterised by the linear sp configuration of the metal7metal bonds and the involvement in the secondary Hg_Hg interactions (2.89 ¡À 3.15A). Note that in the compounds considered in Refs 115 ¡À 120, the bonds between the mercury atoms and the transition metal atoms are, apparently, determin- ing.The Hg7Hg bond lengths (2.65 ¡À 3.27A) are intermediate between the shortened bond lengths found in inorganic and complex compounds of monovalent mercury (2.46 ¡À 2.59A) and the van der Waals Hg2+_Hg2+ contacts (3.41A), which exist, for example, in polymercurated organic derivatives R(HgX)n.122 ¡À 124 VII. Conclusion In the present review, the data on the crystal structures of inorganic and complex compounds of mercury in low oxidation states and on some mercury-containing transition metal clusters containing the (Hg2)2+ pairs and the Hgn groups are summarised.The Hg7Hg and Hg7X bonds (X=O, N, S or Se) are analysed and the modes of coordination of the mercury atoms in the mercury pairs and cluster groups are considered. The crystal chemistry of monovalent mercury compounds is similar to the crystal chemistry of divalent mercury compounds. The ability of the mercury atom to form linear X7Hg7X fragments is retained. However, the sp-bonds in the X7Hg7Hg7X groups are not necessarily exactly collinear. Interestingly, the bonds between the mercury atoms of the (Hg2)2+ pair and the X atom are longer (the average length is 2.14A) than the Hg7X distances in divalent mercury compounds (the average length is 2.06A). The environment about the mercury atoms in the (Hg2)2+ pairs is generally formed by two X atoms.However, the coordination of the pair may be completed by atoms located at larger distances. The instances of the nonlinear coordination about the atoms of the (Hg2)2+ dimers by three X atoms (X=O or N) with the longer Hg7X bonds are mentioned. The Hg7Hg bond lengths in inorganic and complex compounds of formally monovalent mercury vary from 2.46 to 2.59A. An increase in the Hg7Hg bond length is observed in the linear (Hg4)2+ groups (2.59 ¡À 2.63A), infinite Hgn chains (2.64 ¡À 2.67A), (Hg3)4+ triangles (2.60 ¡À 2.70A) and transition metal clusters containing (Hg2)2+ pairs, (Hg3)4+ triangles and Hgn groups. In mixed-valence compounds, the tendency of mercury-oxy- gen groups to polymerisation, which is typical of divalent mercury, is retained.Pairs of formally monovalent mercury atoms form linear O7(Hg2)2+7O groups, which, in turn, form 10-, 12-, 14-, 16- and 22-membered rings in combination with each other and with the linear O7Hg2+7O fragments. The rings are linked in different fashions to form two-dimensional planar or corrugated networks, layers or frameworks. The structures with the 14-membered {[(Hg2)2+]2(Hg2+)4O6} rings are of frequent occurrence. In compounds containing polyatomic groups of mercury atoms, the description of the coordination polyhedra about individual mercury atoms is arbitrary because these polyhedra are substantially distorted due to the presence of the strong Hg7Hg bond.In these cases, it is worthwhile from the crystal- chemical standpoint to consider this series of structures as containing the overall complex Hgn cations (n=2 or 3) with the coordinates of the geometric centres of the complexes and to describe the coordination environment about the Hgx�¢ n cation as a whole. 635 n In the structures of mercury compounds with fluorine and MF¡¦6 anions, the relationships between the value of the averaged formal charge on the mercury atom, the shortest Hg7F distances, the structure of the Hgx�¢ cation and the Hg7Hg distance in this cation are found. As the charge on the mercury atom decreases from +1 to +0.33, the Hg7F distance increases from 2.13 in Hg2F2 to 3.2A in Hg3 NbF6 and the sizes of the Hgx�¢ cations n increase in the series from the finite nearly linear groups to infinite Hgn chains and planar close-packed layers of mercury atoms.The Hg7Hg distances in these cations vary from 2.51 to 2.90A. 4 , Analysis of the structures of inorganic monovalent mercury compounds revealed no substantial effect of the mercury atoms of the (Hg2)2+ pair on the bond lengths in the anions, such as ClO¡¦ 4 , SeO24 ¡¦, PO34 ¡¦ andNO¡¦2 , whereas an elongation of one of the SO2¡¦ bonds with the participation of the oxygen atom, which is bound to the mercury atom of the (Hg2)2+ pair, is observed in com- pounds with the AsO3¡¦ 4 and BrO¡¦3 anions. 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Scand. 21 2743 (1967) 101. T C W Mak, Wai-Hing Yip, C H L Kennard, G Smith, E J O'Reilly Aust. J. Chem. 41 683 (1988) 102. M Sikirica, D GrdeniccZh Acta Crystallogr., Sect. B 30 144 (1974) 103. K Brodersen, J Hofmann Z. Anorg. Allg. Chem. 609 29 (1992) 104. K Brodersen, J Hofmann Z. Anorg. Allg. Chem. 610 46 (1992) 105. W Frank, B Dincher Z. Naturforsch. B, Chem. Sci. 42 828 (1987) 106. F Cecconi, C A Ghilardi, S Midollini, S Moneti J. Chem. Soc., Dalton Trans. 349 (1983) 107. T Tanase, T Horiuchi, Y Yamamoto, K Kobayashi J. Organomet. Chem. 440 1 (1992) 108. E Charalambous, L H Gade, B F G Johnson, T Kotch, A J Lees, J Lewis, M McPartlin Angew. Chem., Int. Ed. Engl. 29 1137 (1990) 109. L H Gade, B F G Johnson, J Lewis, G Conole, M McPartlin J. Chem. Soc., Dalton Trans. 3249 (1992) 110. B Hammerle, E P Muller, D L Wilkinson, G Muller, P Peringer J. Chem. Soc., Chem. Commun. 1527 (1989) 111. P J Bailey, B F G Johnson, J Lewis,M McPartlin, H R Powell J. Chem. Soc., Chem. Commun. 1513 (1989) 112. L H Gade, B F G Johnson, J Lewis,M McPartlin, T Kotch, A J Lees J. Am. Chem. Soc. 113 8698 (1991) 113. Wei Cen, K J Haller, T P Fehlner Organometallics 11 3499 (1992) 114. A Knoepfler, K Wurst, P Peringer J. Chem. Soc., Chem. Commun. 131 (1995) 115. R Kergoat, M M Kubicki, J E Guerchais, N C Norman, A G Orpen J. Chem. Soc., Dalton Trans. 633 (1982) 116. W Gide, E Weiss Angew. Chem., Int. Ed. Engl. 20 803 (1981) 117. N E Kolobova, Z P Valueva, E I Kazimirchuk, V G Andrianov, Yu T Struchkov Izv. Akad. Nauk SSSR, Ser. Khim. 920 (1984) d 118. R A Jones, F M Real, G Wilkinson, A M R Galas, M B Hursthouse J. Chem. Soc., Dalton Trans. 126 (1981) 119. K Wurst, J Strahle Z. Anorg. Allg. Chem. 595 239 (1991) 120. J M Ragosta, J M Burlitch Organometallics 7 1469 (1988) 121. R B King Polyhedron 7 1813 (1988) 122. C Glidewell Inorg. Chim. Acta 36 135 (1979) 123. D Grdenic,M Sikirica, B Korpar-Colig J. Organomet. Chem. 153 1 (1978) 124. D Grdenic, M Sikirica Z. Kristallogr. 150 107 (1979) a�J. Struct. Chem. (Engl. Transl.) b�Crystallogr. Rep. (Engl. Transl.) c�Russ. J. Coord. Chem. (Engl. Transl.) d�Russ. Chem. Bull. (Engl.

ISSN:0036-021X    

出版商:RSC    

年代:1999

数据来源: RSC

摘要:

Russian Chemical Reviews 68 (8) 637 ± 652 (1999) Transformations of organic compounds under the action of mechanical stress AMDubinskaya Contents I. Introduction II. Rupture of intra- and inter-molecular bonds upon mechanical treatment III. Free-radical reactions IV. Oxidation and hydrolysis V. Mechanochemistry of proteins and polypeptides VI. Mechanochemical synthesis VII. Conclusion Abstract. Transformations of organic compounds (monomeric and polymeric) under the action of mechanical stress are consid- ered. Two types of processes occur under these conditions. The first type involves disordering and amorphisation of crystal structure and conformational transformations as a result of rupture of intermolecular bonds. The second type includes mechanochemical reactions activated by deformation of valence bonds and angles under mechanical stress, namely, the rupture of bonds, oxidation and hydrolysis.Data on the organic mechano- chemical synthesis of new compounds or molecular complexes are systematised and generalised. It is demonstrated that mechanical treatment ensures mass transfer and the contact of reacting species in these reactions. Proteins are especially sensitive to mechanical stress and undergo denaturation; enzymes are inactivated. The bibliography includes 115 references. I. Introduction Mechanical treatment of a substance can induce numerous trans- formations, which include, firstly, rupture and formation of valence bonds and deformation of bond angles, and, secondly, both destruction and generation of weaker intermolecular inter- actions (disordering, amorphisation of the crystal structure, conformational transitions and polymorphic transformations).Mechanochemistry started to develop in the 1940 ± 1950s, based on the results of applied studies dealing with polymer processing (plasticisation and rolling of elastomers, grinding of glassy polymers) (see, for example, Refs 1 ± 5). Later, substantial progress has been attained in the mechanochemistry of inorganic compounds (metals, salts, oxides);6± 13 the influence of high pressure combined with shear strain on the rate of solid-state transformations of low-molecular-mass organic compounds has been studied;14 ± 17 the occurrence of mechanochemical reactions in high-energy mills has been discovered;18 ± 21 mechanochemical transformations of coals have been studied;22 free radical reac- tions induced by mechanical stress have been considered;23, 24 and AMDubinskaya N N Semenov Institute of Chemical Physics, Russian Academy of Sciences, ul.Kosygina 4, 117977 Moscow, Russian Federation. Fax (7-095) 938 21 56. Tel. (7-095) 135 80 63. E-mail: str@center.chph.ras.ru Received 9 December 1998 Uspekhi Khimii 68 (8) 708 ± 724 (1999); translated by Z P Bobkova #1999 Russian Academy of Sciences and Turpion Ltd UDC 544.43 : 547 637 637 642 644 645 646 650 experimental studies and theoretical calculations for mechano- chemical reactions involving cleavage of C7C bonds 25 ± 27 and oxidation and hydrolysis reactions have been performed.28 ± 30 (The vast majority of these studies were concerned with solid- phase processes.) A new and fairly promising line of research representing technology of the future, nanotechnology, is closely related to mechanochemistry.A non-traditional application of atomic force and tunnelling microscopes has been reported;31 it was proposed to use them for micro-manipulation, i.e., for positioning atoms and molecules at distances required to initiate a chemical reaction between them (molecular design). Despite the fact that mechanochemistry of organic com- pounds has been successfully developing in recent years (most of the studies in this field were carried out by Russian scientists), the results obtained have not been surveyed; the reasons and the mechanisms of the influence of mechanical stress on chemical processes have not been analysed.The purpose of this review is to fill this gap and to present mechanochemistry (in particular, mechanochemistry of organic compounds) as a field of science developing at the border between chemistry and physics. II. Rupture of intra- and inter-molecular bonds upon mechanical treatment Organic compounds, both polymeric and monomeric, contain bonds of two types, namely, strong interatomic (covalent) bonds within the molecules and relatively weak (van der Waals, hydro- gen) intermolecular bonds. Naturally, the weaker intermolecular bonds should be the first to split under the action of mechanical stress; this results in disordering or loosening of the structure of substances.The degree of disordering depends on the type of mechanical treatment, the amount of energy supplied and the substance structure. Crystalline materials undergo amorphisation and polymorphic transformations under mechanical stress; poly- mers undergo conformational transitions. It should be noted that in the case of polymers, mechanical treatment induces rupture of both types of bonds, because intermolecular bonds are formed along the whole length of polymer chains and the total energy needed to cleave them becomes commensurable with the energy of valence bonds.638 1. Rupture of intermolecular bonds a. Amorphisation of molecular crystals and polymorphic transformations { During fine disintegration of a substance, after the substance particles have reached a particular size, the new surface no longer forms and plastic flow of the substance starts.In some cases, further mechanical treatment results in the particle aggregation. As a rule, the specific surface area (Ssp) of the initial organic crystals falls in the range of 0.1 ± 1 m2 g71; after grinding, it increases several-fold depending on the dose of mechanical energy delivered, the structure of the substance, the presence of moisture, impurities, etc. In some cases, exceptionally high Ssp values have been attained. Thus the specific surface areas attained on grinding of cortisone acetate and saponic acid (based on gas adsorption data) were as high as 130 m2 g71 (see Ref.32) and 400 m2 g71 (see Ref. 33), respectively. These unusually high Ssp values point to extensive disordering (loosening) of the structures of these materials. As a rule, grinding causes a decrease in the degree of crystallinity and sometimes complete amorphisation, which was confirmed by X-ray diffraction patterns and IR spectra recorded for various crystals � ampicillin trihydrate, digoxin, sodium prasteron sulfate,33 sulfanilamides,34, 35 phthalylsulfathiazole,36 sulfathiazole,37 etc. Analysis of the X-ray diffraction patterns of sulfamonomethoxine (Fig. 1 a) allowed the researchers cited 34 to conclude that the observed broadening of diffraction lines is due to both a decrease in the size of crystallites (to *100A) and an increase in the lattice micro-distortions (2 ± 2.5-fold).b a 1 3 2 2 3 dH dt 1 20 10 25 15 190 200 210 T /8C 2y Figure 1. X-Ray diffraction patterns (CuKa radiation) (a) and differ- ential scanning calorimetry curves (b) of sulfamonomethoxine powders after grinding in a jet mill.34 The initial sample (1 ) and the samples having been passed four (2) and six (3) times through the jet mill. Amorphisation increases the rates of dissolution and solubil- ity of compounds;33, 34 it decreases the melting points and heats of melting of crystals and extends the temperature ranges of melting.33 Fig. 1 b presents the variation of the melting point and the heat of melting of sulfamonomethoxine powders as functions of the degree of disintegration found from the data of differential scanning calorimetry (DSC).34 The values for the change in free energy (DG) calculated in two ways, namely, from the decrease in the melting point and the heat of melting and from the increase in the solubility of sulfamonomethoxine on grinding, agree with each other and reach 0.8 ± 0.9 kJ mol71 (see Ref.34). { The data on the influence of mechanical treatment on the properties of low-molecular-mass organic crystals, presented in the review, have been mainly taken from publications devoted to the technology of drugs, which often includes various types of mechanical treatmentfor example, grinding or pressing. AMDubinskaya In some cases, for instance, for fullerene, the peak correspond- ing to a phase transition (*260 K) completely disappears from the thermograms.38 For most of the organic crystal studied, disordering of the crystal structure is associated with disturbance of the system of intermolecular hydrogen bonds, which is confirmed by IR spectra.33, 34, 39 Some organic crystals, for example, barbiturates, streptocid, sulfathiazole, theophylline, cortisone acetate, etc.32, 33, 37 undergo polymorphic transformations on grinding, as indicated by X-ray diffraction, calorimetric and spectroscopic data.In the case of sulfathiazole, mechanically induced reversible transition of the form stable at room temperature into a metastable form occurs (the latter is usually produced by heating the stable form at *174 8C).37 In the case of cortisone acetate, a structure with P21 point group of symmetry passes into a structure with P212121 group of symmetry.32 It was found 31 that under the action of anisotropic compression forces, C60 fullerene is transformed into known carbon phases (diamond, graphite) and into some meta- stable crystalline and amorphous modifications. During the polymorphic transformations induced by mechan- ical treatment, one form does not pass directly into another; this occurs via a disordered non-crystalline state.Upon prolonged mechanical treatment, the new phase arising also becomes amorphised.32, 37 The changes in the physico-chemical properties of substances induced by pressing are similar to those occurring on grinding.Normally, pressing causes a decrease in the degree of crystallinity and polymorphic transformations.33 This has been detected for streptocid, phenylbutazone, chloropropionamide, ephedrine hydrochloride, libexin, noxyron, etc. However, the rate of dissolution of some substances can decrease upon pressing due to the aggregation of powder particles. b. Structure disordering and conformational transitions in polymers As in the case of molecular crystals, the mechanical dispersion of polymers in mills at low temperatures (*80 K) results in sub- stantial disordering (loosening) of their structure caused by loss of the intermolecular van der Waals contacts. This is indicated, for example, by the sharp increase in the adsorption of inert gases by polymers.The specific surface area of dispersed poly(methyl methacrylate) (PMMA) calculated from argon sorption iso- therms is 600 ± 800 m2 g71 (see Ref. 11), and that of poly(methyl silsesqioxane) (PMSSO) is 400 m2 g71 (see Ref. 40) under the same conditions. During unfreezing of a PMMA sample, the disordered structure relaxes even at 120K and the specific surface area diminishes to a value of several square meters per gram. How- ever, in the case of PMSSO, the disordered state is retained during heating of the samples to 500 K. This can be explained by the specific chemical structure of PMSSO; mechanical dispersion of this polymer is accompanied by free radical reactions giving valence cross-links, which stabilise the arising disordered state.40 Crystallisation of solutions (melts) of polymers and separa- tion of liquid phases on exposure to an external mechanical field are phenomena long known in the physical chemistry of poly- mers.41, 42 This is due to the fact that under tensile or shear stress, macromolecular coils are untwisted, the number of contacts between macromolecules increases, and, as a consequence, the degrees of their aggregation and orientation increase. A mechanical action (static compression under 75 ± 100 kbar combined with shear deformation) on crystalline polyoxymethy- lene (POM) induces conformational transitions of various types.43, 44 In particular, a broad range of rotational isomers of chains were found and a phase transition of the hexagonal modification into an orthorhombic one was detected in POM crystals with straightened chains which had been subjected to hydrostatic compression. Evidently, even under conditions of only hydrostatic compression, tangential stresses and micro-Transformations of organic compounds under the action of mechanical stress shears may appear due to the anisotropy of the mechanical properties of the crystals.During mechanical grinding and pressing of proteins, cleavage of hydrogen bonds and disturbance of hydrophobic and electro- static interactions occur, resulting in changed conformations of protein molecules and their denaturation. Mechanically induced denaturation of proteins and inactivation of enzymes are consid- ered in Section V.2. Rupture of valence bonds a. Models of mechanical rupture Rupture of a valence bond on stretching (the simplest mechano- chemical reaction) can be represented as follows.31 Two atoms forming a bond are spaced by distance r0 and are connected by springs to the walls of the surrounding structure. The energy of bond breakage Ubr can be represented as the sum of the potential energy of the bond Ubond and the elastic strain energy Uel of the structure to which the atoms belong. The latter parameter varies as a function of the displacement of atoms from the position where they form the bond towards the equilibrium position with respect to the structure to which they are linked (corresponds to a certain positive value of bond rigidity ks,str) Uel=12 ks,str(Dd7Dr)2, Ubr (Dr,Dd)=Ubond(Dr)+Uel(Dr,Dd ).Here Dr = r7r0 and Dd = d7d0 are the differences between the atom coordinates in the stressed and unstressed states, respec- tively; d0 is the distance between the ends of the spring in the non- stretched state. Figure 2 shows the variation of the potential energy of a C7C bond as a function of Dr for various Dd values. The model parameters used in the calculation have been reported.31 It can be seen from the Figure that as Dd increases, two potential wells appear instead of one well and subsequently they are again replaced by one potential well. As ks,str increases, the potential barrier decreases and finally it entirely vanishes. 1018UC7C /J 2 1 1.0 3 0.8 0.6 0.4 0.20 0.2 0.1 0 Dr/ nm Figure 2.Potential energy of the C7C bond as a function of the distance.31 Dd /nm: (1) 0, (2) 0.1, (3) 0.2. Figure 3 presents plots for the height of the potential barrier U6�� vs the rigidity of bonds of various types for equal depths of the wells.31 When ks,str>90 N m71 and the characteristic times for bond rupture are 51077 s, energy dissipation is small with respect to kT for all types of bonds. In the case of C7C bonds, the requirements to the rigidity are less stringent; it is sufficient that ks,str>60 N m71. In the case of weaker bonds, C7Si and Si7Si, the requirements are even lower. The kinetic theory of the strength of solids, apart from the purely mechanical rupture of interatomic valence bonds induced by an external force, takes account of the destructive role of thermal motion, i.e.cleavage of interatomic bonds is caused by 639 1021U6�� /J 100 C7O 80 60 C7N C=C 40 20 O7O N7N Si7Si C7SiC7C 0 120 80 40 160 ks,str / N m71 Figure 3. Height of the potential barrier for the stretching of bonds vs their rigidity.31 energy fluctuations arising due to the thermal motion of atoms rather than by the external force itself.45 According to a concept developed in a publication 45 (thermofluctuation mechanism), two elementary stages should be distinguished in the bond rupture, namely, (1) force perturbation of interatomic bonds in a loaded body, which decreases the energy barrier to the bond cleavage and (2) splitting of stressed bonds upon thermal fluctuations. , Ea ¡¦ sva RT k �� k0exp The rate constant for the bond rupture k can be calculated from the equation where k0 and Ea are the preexponential factor and the activation energy for the thermal bond rupture, respectively, s is the mechanical stress and va is the unit activation volume.The rupture of valence C7C bonds in polymers has been studied most comprehensively (both theoretically and experimen- tally). The deformation of valence bonds in stretched samples of oriented linear polymers (polypropylene, polyamide, polytetra- fluoroethylene, etc.) has been observed by IR spectroscbsorption bands corresponding to stretching vibrations of the C7C bonds in the polymer backbones shift to lower frequencies upon stretching. The band contours for stressed (stretched) samples also change.According to estimates,45 the maximum loads of individual bonds in polymers attained on stretching are 10 ¡À 20 GPa. The thermofluctuation elementary events of destruc- tion occur within small activation volumes (commensurable with the volume of atoms) upon great overstress. It has been assumed 46 ¡À 48 that not only rupture of stretched bonds can be induced by thermofluctuations in a stressed polymer but also self-ionisation of macromolecules accompanied by ejection of electrons. A calculation of the electronic spectrum of a macromolecule with stretched C7C bonds showed 47 that the elongation of a bond gives rise to a local electron level; its energy for a factor of two elongation is *4 ¡À 5 eV, which is close to the energy of charge separation in a polymer.The electrons having been liberated under the action of mechanical stress can be captured by traps (molecules with large electron affinity, structure defects) and are again released when the traps have been destroyed; this accounts for the mechanical emission of electrons, which has been found to accompany stretching of films and grinding of some polymers [polyethylene (PE), polyethylene terephthalate] and organic crystals.46, 48, 49 The decrease in the ionisation potential of molecules subjected to mechanical stresses has been described by quantum-chemical methods.27, 30 Figure 4 shows the calculated plot for the variation of the ionisation potential I as a function of bond angles in the propane molecule.27 It can be seen that an increase in the deformation of the molecule results in lower I values.640 E /eV 2 12 H b H C 10 CH3 H3C a 3 86 1 H b H 4 C 2 H3C CH3 a 120 80 160 a /deg Figure 4.Quantum-chemical calculation for the change in the ionisation potential upon deformation of bond angles a and b (a=b ) in the propane molecule.27 Curves (1) and (2) show the potential energy (E) of propane and its radical cation, respectively; curve (3) is the difference between curves (2) and (1). Apart from the mechanical emission of electrons, some other experimental results cannot either be interpreted in terms of the thermofluctuation mechanism.Firstly, the compositions of the molecular products of thermally and mechanically induced destructions are different.25, 26, 45 The products of mechanical destruction contain no heavy fragments of polymer chains, which are typically present in the case of thermal degradation. The formation of light products on mechanical destruction indicates that the vibrational energy is distributed non-uni- formly, being located in regions with a size of not more than 10A. Secondly, mechanical destruction of some polymers (PMMA, the three-dimensional epoxy polymer based on digly- cidyl ether of resorcinol and meta-phenylenediamine, and ebonite) has been found to give high-energy molecular products.25, 26 The kinetic energy of these species was estimated using the time-of- flight mass spectrometer equipped by a device for high-speed detection of molecules.The velocity of the flight of the molecular products formed was used to calculate the translation temper- ature, which amounted to 2000 ¡À 5400 K for the above-mentioned polymers. The appearance of vibrationally excited states upon destruc- tion of a PMMA sample was confirmed by thermal radiation spectra.50 It can be seen from Fig. 5 that radiation consists of two components D Planck's radiation and a characteristic narrow emission band at 8.3 mm, which appears 10 ¡À 60 ms after the sample fracture; this band is related to deactivation of the vibrationally excited centres, which arise during destruction of the sample and whose nature is unknown.Analysis of the spectra l (rel. u.) 3 4 21 2 8 6 4 10 l/mm Figure 5. Heat radiation spectra recorded during fracture of a PMMA sample.50 Time elapsed after the onset of destruction 10 (1), 20 (2) and 30 ms (3). AMDubinskaya obtained led to the conclusion that the average warming of the sample during the polymer fracture does not exceed 200 8C. In a series of publications (see a review 25 and the studies cited therein), the destruction of a stretched chain of atoms has been studied by methods of molecular mechanics. Studies 25 ¡À 27 on mechanodestruction of one-dimensional models of polymer chains consisting of 50 and 100 carbon atoms led the researchers to the conclusion that solitons play the crucial role in mechano- destruction.Over a long period (*10 ps) after the rupture of a stretched chain, the elastic energy stored in the chain is not thermalised and no thermal fluctuations (in the generally accepted sense 45) occur. It was shown that movement of high- energy solitons may be accompanied by the formation of C7C double bonds and by discharge of the side-chain atoms. It was shown that rupture of one chain may yield several high-energy molecular products capable of inducing destruction of the adjacent polymer chains; thus, chain branching is possible. All the models for bond rupture known to date are one- dimensional and are restricted to the views of classical mechanics. Only the first attempts to pass from one-dimensional to two- dimensional models have been undertaken.51 Nevertheless, the one-dimensional chains considered above can be accepted as a satisfactory approximation to real linear macromolecules.Description of the mechanically induced bond rupture in three-dimensional systems (cross-linked polymers and low-molecular-mass crystals) is a more complicated task, none of the models presented being suitable for this purpose. b. Formation of free radicals Free radicals resulting from the rupture of valence bonds during mechanically induced destruction of many polymers and some low-molecular-mass compounds have been detected by EPR.23, 24, 52 The appearance of `mechanical' macroradicals was observed on stretching of films and fibres and on grinding of linear and three-dimensional polymers in a mortar, in a mill, etc.The EPR spectra of `mechanical' macroradicals have been thoroughly studied, which permitted identification of the type of bond being cleaved in each polymer; it was found that the covalent bonds in the polymer backbones and cross-links (or bridges) undergo homolytic cleavage. Thus vinyl polymers [PE, polypropylene, poly(methyl acrylate), PMMA, polystyrene (PS), etc.] and poly- peptides [poly(amino acids), proteins] undergo cleavage of C7C bonds; in the case of carbon-and-oxygen polymers [polyformal- dehyde, poly(ethylene oxide), polyesters and three-dimensional polyesteracrylate], C7C and/or C7O bonds are split; for ladder and three-dimensional network organosilicon polymers [PMSSO and polyphenylsilsesquioxane (PPSSO)], rupture of the Si7O bonds is observed, and in some polypeptides (trypsin, insulin, serum albumin), cleavage of C7C and C7S bonds occurs. When polymers are subjected to mechanical treatment in a mill, the rate of accumulation of macroradicals (dR/dt) in the beginning of the process is constant and then it gradually decreases and approaches zero; thus, the concentration of macro- radicals reaches a limiting value.The kinetics of radical accumu- lation are described by the equation 24 (1) dR dt �� Wd ¡¦Wr , whereWd is the rate of bond rupture, equal to kd[M];Wr is the rate of the decay of radicals upon interaction with one another, equal to kr[R]2; [M] is the concentration of bonds that can be cleaved; [R] is the concentration of macroradicals; kd and kr are effective rate constants for these reactions in the solid phase (see below).At the beginning of the mechanical grinding when Wd Wr , (dR/dt)0%Wd , i.e. when the intensity of the mechanical energy supply is constant, the rate of destruction depends only on the polymer nature. The rate of destruction in laboratory vibrational mills with energy input of 1 ¡À 10 W g71 at temperatures of 100 ¡À 300K amounts to 1014 ¡À1016 g71 s71. The steady-state cntration of free radicals [R]lim (for dR/dt = 0) in linearTransformations of organic compounds under the action of mechanical stress flexible-chain polymers is (1 ± 5)61018 g71 and that for rigid- chain (especially three-dimensional) polymers is 1019 ±1020 g71.The relative rates of destruction of various polymers during grinding under identical conditions are compared in Table 1. The rate of bond rupture is determined, first of all, by the rigidity of the structure. It increases on passing from flexible-chain PE to more rigid PS and then to polypeptides, the structures of which are noted for special rigidity owing to the presence of peptide bonds in the backbone and a dense network of hydrogen bonds. The maximum destruction rates were detected for three-dimensional polymers (glyceromaleate, a,o-diethylene glycol phthalatedime- thacrylate). Table 1. Relative rates of mechanical destruction of polymers at T'100 K. 24 Polymer (dR/dt)rel (see a) Mn Mw 1 17 20 777 290 000 300 000 450 0007 7 120 30 55 45 4061.5 777777 PE PS PPSSO PEMb Collagen Subtilisin Serum albumin Trypsin Insulin Gramicidin 290 000 27 000 67 000 24 000 5 733 1 140 a The rate of destruction of PE was taken to be unity.b PEM is a cross-linked polymer of a,o-diethylene glycol phthalatedi- methacrylate. The rate of mechanical destruction and, hence, of the formation of free radicals decreases with a decrease in the molecular mass of the polymer. Thus the rate of formation of radicals in insulin, which has the lowest molecular mass among the series of proteins studied, is 7 ± 9 times lower than those in other proteins. The question of the limiting molecular mass Mlim or the limiting degree of polymerisation nlim below which the mechan- ical destruction of covalent bonds is terminated and only weak intermolecular bonds are broken has arisen repeatedly in the mechanochemistry of polymers.1, 24 The nlim value depends on the chemical structure of the polymer and the relationship between the strengths of valence and intermolecular bonds and can be roughly estimated from the expression (2) U=nlimUcoh , whereUis the strength of a valence bond being cleaved andUcoh is the cohesion energy for a monomer unit.Expression (2) does not take into account the structural inhomogeneity of a real polymeric material and the stress gradient. The cohesion energy is especially large for polymers which contain hydroxy, carboxy, amino and other groups which form intermolecular hydrogen bonds (for polypeptides Ucoh reaches 40 ± 50 kJ mol71 per amino-acid residue).For these polymers, low nlim and Mlim values should be expected. Indeed, for poly- ethylene nlim^100, while in the case of polypeptides, nlim^6. Therefore, free radicals have been detected after mechanical treatment of relatively low-molecular-mass cyclopeptides con- taining only ten (gramicidin) and twelve (bacitracin) amino-acid residues in the ring.52 Free radicals are formed when some low-molecular-mass organic compounds are subjected to high pressure together with shear deformation. To detect the radicals, a special resonator has been designed for an EPR spectrometer, which acts simultane- ously as one of the anvils.16, 17, 53 Thus in arylindandione dimers 641 O X R 2 O X=H, Cl, NMe2; R = p-Me2NC6H4 destruction involves the Ca7Ca bond, the strength of which (U^70 kJ mol71) is comparable with the Ucoh value.It was found that hydrostatic pressure (up to 0.7 GPa) without shear strain does not induce the formation of radicals, i.e. it is the shearing component of the mechanical stress that causes the bond rupture. Fig. 6 shows the dependence of the yield of free arylindan- dione radicals (in relative units) on the angle of rotation of the anvils at a constant pressure.16 When the angles of rotation are small, the yield of radicals rapidly increases (curves 1, 2, the linear section), i.e. the radical generation process predominates.An increase in the angle decreases the yield of radicals and their recombination starts to predominate. Ultimately, as in the case of mechanodestruction of polymers (see above), the concentration of radicals reaches a limiting value. n/n0 15 1 10 2 50 20 40 a/ deg Figure 6. Yield of arylindandione radicals vs angle of rotation of the anvils a at a pressure of 7 (1) and 12 kbar (2);16 n0 is the initial concentration and n is the current concentration of reacting species. Under the same conditions, the EPR spectrum of C60 fullerene was found to exhibit a signal which was assigned to the carbon radicals formed upon destruction of the C60 molecules.53 The rate of generation of these radicals is comparable with the rate of generation of arylindandione radicals (*1016 g71 s71).Indirect evidence pointing to the cleavage of valence bonds to give free radicals has been obtained under the action of an indenter, shock waves and vibratory grinding of the crystals of (1016 g71) of N .O2 radicals were detected by EPR spectroscopy some nitro compounds.49 For example, minor concentrations upon vibratory grinding of pentaerythritol tetranitrate or cyclo- trimethylenetrinitramine. It was suggested 49 that in this case, the formation of paramagnetic centres is related to the effect of the radiation which arises upon the fraction of crystals. To elucidate the reasons for the appearance of paramagnetic species more precisely, further studies are required.Mechanical destruction in the solid phase can be represented as a sequence of the following stages:54, 55 km ki R7R (R_R.) R.+R., . and the effective rate constant for the destruction, kd, can be represented as follows:642 k (3) d a kmkiv . km a ki The first stage is a reaction characterised by the rate constant ki and resulting in the formation of (R._R. ) radicals, which occur in unit volume or in cage v. The km constant characterises departure of the radicals from the cage. The molecule in the pre- rupture state is stretched, and after bond cleavage, the radicals are removed from each other and leave the unit volume. The rupture of the bond rather than the emergence of the radicals from the cage is the limiting step in the destruction, i.e., ki km .III. Free-radical reactions The free radicals having formed upon the mechanical destruction enter into ordinary free-radical reactions �¢ recombination, decomposition, addition and substitution. The reactions occur- ring in the field of mechanical stress should be distinguished from those proceeding after the field has been removed (post-effect). The former type of reaction would involve most likely mechan- ically activated species. In addition, mechanical treatment causes plastic deformation of the material and migration of particles. In the latter type of reaction, the role of mechanical action reduces mostly to the generation of radicals, while the subsequent free- radical processes obey the rules inherent in them. Virtually all of the mechanochemical free-radical reactions described to date occur in the solid phase; therefore, the specific features of the kinetics of solid-phase reactions should be taken into account.1. Recombination The elementary step of radical interaction (recombination) in the solid phase is preceded by the step in which they approach each other. This can occur either as chemical migration of a free valence or as physical migration of the reacting species.23, 24 In the former case, recombination is a complex process consisting of separate elementary steps. (Some of these reactions are considered below.) In the latter case, recombination kinetics are determined by the mobility of radicals.The decay of macroradicals in a polymer matrix having been subjected to mechanical grinding occurs near the glass transition temperature Tg .24 At this temperature, the segmental mobility of the polymer chains is unfrozen and the radicals become able to move large distances and meet one another. The decay of radicals in the field of mechanical stress, i.e. under conditions of forced mobility of reacting species, is a specific case. The effective rate constants for recombination of free radicals during grinding in a mill can be estimated from the kinetics of accumulation of free radicals.24, When dR/dt=0, the rate constant for recombination kr has the form [see Eqn (1), Section II.2.b] k lim r a Wd . aRa2 Depending on the nature of the polymer and the energy input of the mill, the kr values at 100 ¡¾ 300K range from 10724 to 10721 cm3 s71.Radical recombination can be represented by the following scheme: ki km molecular products. R.+R. (R._R.) In the step characterised by the constant km , the radicals approach each other under the action of plastic deformation caused by mechanical stress. Using Eqn (3) provided that km ki, we obtain kr = kmv. The volume of a cage v is approximately 5610722 cm3, and the frequency of the trans- lation of radicals during mechanical treatment of the material in the mill (80 ¡¾ 100 K) is 1073 to 1 s71. AMDubinskaya Recombination of radicals in the solid phase is characterised by a distribution of rate constants with the boundary values kmax and kmin .This may be due to the fact that the local reaction conditions �¢ the size of the cage, mutual orientation of the reacting species, the closest environment, etc.�¢ are differ- ent.16, 53, 56 ¡¾ 58 Species interacting in any system can be character- ised at any instant by the distribution function n(k,t)dk, which determines the number of species that react in unit volume at instant t with a rate constant k (kmin4k4kmax). Since species can migrate between various fractions of the distribution function (i.e., between states with different k), it becomes `intermixed'. The form of `intermixing' of the distribution function is determined by the processes that induce the changes in the kinetic properties of the reacting species.In particular, mechanical dispersion brings about `mechanical intermixing' of the distribution function.58 If mechanical intermixing results in the reaction rate constant k becoming equal to kmax , this means that the reaction occurs under kinetically controlled conditions. However, a different regime when kmin k kmax and the reaction is controlled by diffusion is more frequently encountered in practice. ¢§1 ln kmax n n O¢§ ln kmin ¢§ ln n0tU. a kmin 0 The post-effect recombination can be described satisfactorily by equations of polychronous kinetics.16, 53 The difference between kmax and kmin for arylindandione radicals reaches five orders of magnitude. The kmax value depends only slightly on the pressure applied and on the angle of shear and is approximately 5610720 cm3 s71.Thus, shear strain and pressure scarcely influence the rates of the fastest reactions but do influence the rates of the slowest ones. Obviously, the formation of free space and creation of a favourable arrangement of radicals are the limiting steps for radical recombination. 2. Radical decay It is known24, 59 that mechanical treatment of polymers is accompanied by decay of macroradicals. In macroradicals, the bond located in the b-position to the unpaired electron is weakened; the activation energy for the rupture of this bond in and in some cases [e.g. in the 7CH2C .MeX radicals in PMMA hydrocarbon radicals in the gas phase is about 100 ¡¾ 120 kJ mol71 (X=CO2Me) and polyisobutylene (X=Me)], it decreases to 50 ¡¾ 70 kJ mol71. Mechanodestruction of polyformaldehyde, polyisobutylene and polyorganylsiloxanes at low temperatures, i.e.under condi- tions when the thermal decay of macroradicals occurs at an extremely low rate, has been found to give light volatile prod- ucts.24, 60 Thus the light products of mechanodestruction obtained by grinding of PMSSO in a mill at temperatures of 4200K include mostly hydrogen, methane and ethane; those in PPSSO consist of hydrogen and benzene.60 R RSi O Si O O O Si Si R R R=Me (PMSSO), Ph (PPSSO). imply that hydrogen atoms and C .H3 and C . 6H5 radicals are The compositions and the conditions of formation of products formed during the mechanodestruction. Presumably, the mechan- ical destruction of polymers gives rise to vibrationally excited macroradicals, which then decompose to yield low-molecular- mass radicals.Thus destruction of PMSSO involves the following processes:Transformations of organic compounds under the action of mechanical stress [Si O]+CH3, Si(CH3) O* O O * Si CH3 Si CH2 + H . O O The formation of hydrogen atoms was proved experimentally. Figure 7 a shows the kinetic curves for the formation ofH2 and CH4 and for the accumulation of free radicals (R. ) during destruction of PMSSO. The diffusion of light species (H. and C .H3) results in migration and decay of the free valence; therefore, hydrogen atom has been considered theoretically using the model The influence of mechanical stress on the free-radical transfer of a the amount of macroradicals observed in the destruction of PMSSO is always lower than the amount of monomeric products (per g of the polymer).The evolution of hydrogen and the formation of CH4, C2H6 and R. are compared in Fig. 7 b; the plot was constructed using the results of a large number of experiments, in which the intensity of destruction of PMSSO varied by a factor of up to 50 (various conditions of mechanical treatment � duration of grinding, design of the working vessel, etc., were used). Irrespective of the destruction intensity and dispersion conditions, the total amount of the volatile products evolved in the PMSSO destruction exceeds*4.5-fold the number of free radicals observed.The overall rate of formation of low- molecular-mass radicals (H. and C .H3) is higher than the rate of formation of macroradicals by a factor of 8 ± 9. These data attest to a very high (*0.9) probability of decomposition of `hot' macroradicals. b a 10722 c /kg71 log c 2 2 8 23 1 6 22 3 4 3 21 2 1 20 21 20 40 t/ min 20 22 log [H2] Figure 7. Kinetics of accumulation of radical and molecular products (a) of the mechanical destruction of PMSSO and comparison of their concentrations (b);60 (a) (1) [R. ], (2) [CH4], (3) [H2]; (b) (1) [R. ], (2) [CH4], (3) [C2H6] (different designations refer to different rates of formation of hydrogen and different conditions of mechanical destruction).In the case of PPSSO, the rates of formation of volatile products and free radicals are commensurable and the total rate of formation of low-molecular-mass radicals (H. and C . 6H5) is sharply increases and at T>200K the reaction rate cannot be reaction rate scarcely depends on the temperature; at T>150 K, it twice as high as the rate of formation of macroradicals; the probability of decomposition of `hot' radicals for PPSSO is about 0.6 ± 0.7. The mechanical treatment of polymers yields internal macro- radicals, i.e. radical products of interaction of the primary terminal macroradicals with surrounding macromolecules (see Section III.3). It has been assumed that the internal macroradicals decompose during mechanodestruction to give terminal radicals and unsaturated compounds; after that, the terminal radicals interact with macromolecules to give internal macroradicals, i.e.a chain reaction occurs.61 However, experiments with polyethy- lene samples containing high concentrations of internal radicals, prepared by exposure of the samples to radiation, demonstrated that the role of mechanically induced destruction of internal 643 radicals is relatively insignificant, recombination being the main pathway for the decay of these radicals.62 This may be due to the non-uniform distribution of elastic energy among individual bonds in an amorphous solid; as a consequence, the ratio between the rates of rupture of weakened bonds (in the internal radicals) and normal bonds in macromolecules is determined by the probability of energy localisation on these bonds rather than by the ratio of their strengths.3. Hydrogen atom transfer of the symmetrical process (4) H3CH+.CH3 , H3C.+HCH3 which occurs under normal conditions with a high activation energy ('60 kJ mol71). 31 The calculation of the influence of methane compression on the height of the barrier to reaction (4) showed that within the framework of this model (extended LEPS potential and ab initio calculation methods), at a compressrce of 3.6 nN, U6à=0. However, at room temperature, there is no need to diminish the barrier to zero. Thus at a compression force of 1 nN, U6à^18 kJ mol71 and the reaction proceeds at room temperature at a plausible rate.The influence of tensile stress on the rate of hydrogen atom transfer is considered in Section IV in relation to the reaction of ozone with polyolefins. The following method proved to be fruitful for studies of low- temperature free-radical reactions:24 solutions of polymers frozen at 80 ± 100K were subjected to mechanical dispersion in a vibratory mill; the role of mechanical treatment reduced mainly to the generation of free radicals and ensuring the mass transfer and the contact between the reacting particles. It was found that reactions proceed both during treatment of mixtures in the mill and after the mill has been switched off and the temperature has increased. A series of reactions involving carbon-centred and peroxyl radicals (which are readily formed when carbon-centred radicals contact with atmospheric oxygen) have been found.For instance,24 it was shown that at low temperatures (*100 K), macroradicals abstract hydrogen atoms from various types of bonds, O7H (phenol), N7H (primary and secondary amines), S7H (benzenethiol and phenylmethanethiol) and C7H (alkylbenzenes, acetonitrile, malonic acid). The C7H bonds are especially strong and reactions involving these bonds are charac- terised by high activation energies (>30 kJ mol71). The rate constants were found to be 4 ± 6 orders of magnitude greater than those calculated from the data obtained for the liquid phase at elevated temperatures. The kinetics of the reaction of the macroradicals formed upon destruction of PS, polyvinyl acetate, etc., with malonic acid (5) RH+.CH(COOH)2 R.+CH2(COOH)2 was studied 24 over a broad temperature range (100 to 200 K) (Fig.8). It can be seen from the Figure that at 100 ± 150 K, the measured because it is too high.24 The experimental rate constants for hydrogen atom transfer are in good agreement with those calculated with allowance for the tunnelling of hydrogen through the potential barrier. The hydrogen atom transfer determines the migration and stabilisation of radical states in polymers. Thus it is known 23, 24 that the radical products of mechanical destruction of polymers contain, even at low temperatures (*80 K), internal macrorad- icals, resulting from abstraction of hydrogen atoms from polymer chain units.Yet another example of hydrogen atom transfer in polymers is provided by the reaction of peroxyl radicals with macromolecules, which is the rate-determining step in the low-temperature oxida- tion of polymers.58644 log k+5 2.0 1.2 0.4 10 12 103 T71 8 6 4 Figure 8. Temperature dependence of the rate constant for reaction (5).24 The circles show the experimental results and the curve is based on calculations with application of the tunnelling correction. ROOH+.R0 ROO.+R0H and kmin=1.361012 exp kmax=3.86108 exp ¡¦ 88 RT ¡¦ 43 RT This reaction was studied for PMMA and PS over a wide temperature range in vacuo after termination of mechanical treatment.As for other reactions occurring in the solid phase, in this case, too, kinetic non-equivalence of the reacting species was discovered; the distribution function of the `mechanical' peroxyl radicals inPMMAand PS over rate constants at 210 ¡À 300Khas a hyperbolic shape 58 (see also Section III.1). For instance, in polystyrene, the rate constants for individual fractions of the distribution function can differ by ten orders of magnitude: (the activation energy is expressed in kJ mol71). Thus, study of mechanochemical reactions of hydrogen atom transfer resulted in the elucidation of interesting specific features of the reaction kinetics, namely, tunnelling of a hydrogen atom at low temperatures, non-equivalence of the reacting species in the solid phase and `mechanical intermixing' of the distribution function.However, no influence of mechanical stress on the activation energy for the hydrogen atom transfer was found. 4. Addition A study of mechanical treatment of mixtures of polymers with monomers in a vibratory mill provided experimental data on the Experimental data on the acceleration of oxidation of poly- addition of free radicals to C=C bonds. 24 It was found that at 80 ¡À 100 K, the 7CXX0C .H2 and 7CH2C .XX0 macroradicals hydrolysis of polycaproamide are shown in Fig. 9 b; these results propylene by ozone are presented in Fig. 9 a, and the data for the (X=H, Me; X0=Ph, CO2Me, OCOMe) readily enter into the reaction R.+CH2=CXX0 . RCH2CXX0. Under the same conditions, carbon-centred and silyl macro- radicals add to benzene and its derivatives to give radicals of the cyclohexadienyl type,63, 64 for example, H .Si Si +C6H6 H The kinetics of the reaction . 7CH2C(Me)CO2Me +CH2=CHPh. 7CH2C(Me)(CO2Me)CH2CHPh, which occurs on mechanical treatment of the initial compounds in a vibrational mill, has been studied in the 80 ¡À 143K temperature range. 24 At 80 K, the reaction does not proceed, and at 113 ¡À 143K the dependence of the rate constant on the temper- ature obeys the Arrhenius equation. The activation energy for the AMDubinskaya reaction (21 kJ mol71) is close to the activation energy for the same reaction in the liquid phase at 280 ¡À 330 K. Thus, no mechanochemical effects were found in the studies of addition reactions with relatively low activation energies.Appa- rently, these effects could be found for reactions with higher activation energies. The role of mechanical stress in free-radical reactions studied to date is to initiate the formation of macroradicals and to ensure mass transfer (to let the reagents meet each other). No influence of mechanical treatment on the activation energy of these reactions was found. IV. Oxidation and hydrolysis The influence of mechanical stress on the potential barriers can be clearly followed for some reactions (oxidation, hydrolysis). Acceleration of oxidation under tensile stress was discovered by Kuz'minskii et al. back in 1953 (oxidation of elastomers by atmospheric oxygen).65 Krisyuk et al.28, 30 carried out oxidation of polyolefins by ozone.ROH+O2 [R.+HO.+O2] RH+O3 The oxidation (sorption of ozone and formation of free radicals) of oriented polypropylene films is accelerated 2 ¡À 5-fold when a tensile stress s ranging from 33 to 145 GPa is applied. Mechanical stress accelerates hydrolysis of polyamides; this was first observed by Bershtein 66 and then studied by Krisyuk et al.29, 30 Both the oxidation of polyolefins with ozone and the hydrolysis of polyamides are accelerated on stretching of these polymers according to an exponential pattern (in the temperature range of 328 to 369 K) (6) ln k �� as RT , k0 where k0 is the rate constant for the reaction (k) in the absence of tensile stress s.The constant a characterises the sensitivity of the reaction to stress and depends on the polymer structure. This constant is defined by the equation (7) a=f(l 6��7l0)s, where f is the overstress coefficient, which depends on the structure of the polymer material, l 6�� and l0 are the lengths of the reaction fragment in the transition and initial states, respectively, and s is the cross-section of the molecule. confirm the validity of Eqn (6). b a log (k/k0) ln (k/k0) II 1.0 1.0 I 0.5 0.5 12 12 0 0 5 10 5 1074 (s/RT) /mol m73 Figure 9. Rate constants for ozonisation of polypropylene (a) at 291 (1) and 313K (2) and for hydrolysis of polycaproamide (b) at 393 (1) and 113K(2) vs mechanical stress.30 The stretching ratio of the samples is 6 (I ) and 3 times (II ).Transformations of organic compounds under the action of mechanical stress It has been shown 28 that an increase in the rate of polyolefin oxidation cannot be explained either by the change in the diffusion and sorption parameters, or by the change in the molecular mobility, or by destruction of polymer chains.The change in the reactivity of the C7H bonds in polymer chains is caused by stretching and is similar toon with the abstraction of hydrogen atoms from strained rings.67 When a hydrogen atom is eliminated, the sp3 hybridisation of the carbon atom changes to sp2, resulting in a greater bond angle. This brings the structure closer to a transition state and, as a consequence, accelerates the reaction. The acceleration of hydrolysis of polyamides can be inter- preted at a qualitative level in a similar way.The C7N bonds in polyamide are strengthened due to delocalisation of the p electrons of the carbonyl groups, which interact with the nitrogen p orbitals. On stretching, the interacting orbitals move apart, the conjugation is violated and hydrolysis occurs faster. The effect of stretching resembles the influence of substituents in conformity with the Hammett ± Taft equation. Quantum-chemical calculation 30 for the cross-section of the potential energy surface for some monomers modelling polymer chains (methane, propane, butane) has shown that stretching of molecules weakens the C7H bonds.When the molecule is stretched, the energy of the initial state increases to a greater extent than the energy of the transition state, resulting in a lower activation energy for the reaction. Thus, the calculation showed that the C7Hbond is actually activated and that the sensitivity of a reaction to deformation increases with an increase in the strength of this bond and with a decrease in the activity of the hydrogen acceptor. (8) The change in the activation energy of a reaction under the influence of a force f is described by the equation DEa=f (l 6à7l0). It follows from Eqns (6) ± (8) that stretching of molecules would accelerate those reactions in which the formation of the transition complex is accompanied by elongation of the reactive fragment.Conversely, processes accompanied by a decrease in the length of this fragment should be retarded on stretching. V. Mechanochemistry of proteins and polypeptides The necessity of developing the mechanochemistry of proteins and polypeptides can hardly be overstated; indeed, study of the mechanochemical transformations provides a key for the under- standing of some phenomena occurring in living cells and organisms. During preparation of food, medicines, etc., proteins undergo various types of mechanical treatment (grinding, press- ing); this can change their structures and properties. The main mechanochemical processes occurring in proteins include rupture of covalent bonds in polypeptide chains, mechan- ically activated hydrolysis of peptide bonds and destruction of weak intermolecular bonds.Mechanical treatment can also change the catalytic activity of protein enzymes. 1. Mechanical destruction of covalent bonds Mechanical treatment (grinding, stretching) of samples of poly(amino acids) (polyalanine, polyleucine, polyvaline), fibrillar proteins (collagen, silk), globular proteins (trypsin, subtilisin, serum albumin), oligopeptides (gramicidin, bacitracin) has been found (EPR data) to yield free radicals,24, 52, 68 ± 70 the EPR spectra in gelatin, collagen, silk, serum albumin, etc. having much in common despite the different amino-acid composition of the proteins. The experimental data accumulated by now permitted determination of the structure of the resulting free radicals and the type of bond being cleaved.Based on the analysis of spectral characteristics of the radicals resulting from mechanical treatment of polypeptides at *80 ± 100K and their transformations on heating to 645 200 ± 250K52 and on exposure to light, 69 one can conclude that the C7C bonds are cleaved predominantly. 7C(O)NHCaHRC(O)NHCaHR7 . . 7C(O)NHCaHR+C(O)NHCaHR7. Initially, this affords reactive terminal radicals, which then react with polypeptide chains to give internal radicals.52 R .+7C(O)NHCaHR0C(O)NHCaHR07 . RH+7C(O)NHCaR0C(O)NHCaHR07 The abstraction of hydrogen from the carbon atom in the a-position with respect to the CO group is accompanied in some cases (e.g. in polyleucine) by its transfer from side substituents to give7NHCH(CH2C .Me2)C(O)7.52 In the case of trypsin, albumin and insulin, the mechanically induced cleavage of the polypeptide backbones is accompanied by rupture of theC7S bonds.52 TheC7S bonds are weaker than the C7C bonds and are destroyed more rapidly. The proportion of sulfur-centred radicals, R . S, ranges from 14% to 20% of the total number of radicals formed. In the presence of atmospheric oxygen, carbon-centred radicals (both terminal and internal) are oxidised, being thus converted into peroxyl radicals. Sulfur-centred radicals are stable and are retained unchanged up to 340 ± 360 K, when they become sufficiently mobile to recombine. The rate of formation of free radicals in proteins is higher than that in linear synthetic polymers (see Section II.2.b and Table 1).The rate of mechanical destruction of collagen was calculated from the rate of accumulation of free radicals and compared with the rate of decrease in the molecular mass of this protein calculated from electrophoresis data.70 The rates of rupture of the covalent C7C bonds in collagen dispersed in a micromill (80 ± 90K) or in a vibratory mill (100 ± 150 K) amount to 1.561015 and 8.061015 bonds g71 s71, respectively (EPR data) or 1.861015 and 9.661015 bonds g71 s71, respectively (electro- phoresis data); i.e. the values found by two independent methods are in satisfactory agreement with each other.70 The above data confirm the assumption that homolytic cleavage of the polypeptide chain is the main source of free radicals during the mechanical grinding of proteins. 2.Mechanically activated hydrolysis As shown above (see Section IV), polyamides readily undergo mechanically activated hydrolysis. The possibility of this type of hydrolysis in proteins was demonstrated in relation to trypsin;71 the sample obtained by mechanical dispersion of this compound at 295K was found to contain hydrolysis products, namely, N-terminal amino acids (glycine, tyrosine, serine and glutamic and aspartic acid). When trypsin was dispersed at a low temper- ature (*80 K), amino acids were not formed. 3. Breaking of weak intermolecular contacts The breaking of weak intermolecular contacts (hydrogen bonds and hydrophobic and electrostatic interactions) brings about conformational transitions and disordering of the protein struc- ture; in our opinion, this is the main reason for mechanical denaturation (both reversible and irreversible).The conforma- tional transitions have also been studied for globular proteins (trypsin, subtilisin)71, 72 and for fibrillar proteins with rod-like molecules (collagen).73 Curves 1 and 2 of Fig. 10 show the decrease in the intrinsic viscosity [Z] of collagen upon mechanical destruction.73 Curve 1 was constructed using experimental data and curve 2 was calculated from the equation [Z]=1.2361079M1.8, where M is the molecular mass of the polymer after mechanical destruction. It was assumed that the change in the viscosity of a646 [Z], [a]D (rel.u.) 1.0 0.8 0.6 3 0.4 2 0.2 1 0 10 t /min 8 4 Figure 10. Variation of some properties of collagen during mechancal grinding;73 (1) and (2) decrease in the intrinsic viscosity [Z] (1 is experimental curve, 2 is calculated curve); (3) decrease in the specific optical rotation [a]D . solution of collagen is entirely due to the decrease in the size of macromolecules caused by the rupture of covalent bonds during grinding, while the shape of the molecules remains unchanged. However, the experimental values are much smaller than the calculated ones, which might imply that the rod-like shape of macromolecules has changed. One more piece of evidence for the change in the shape of collagen macromolecules is the substantial decrease in the specific optical rotation [a]D for large degrees of grinding (see Fig.10, curve 3).73, 74 A clear representation of the change in the rod-like shape of collagen molecules (the appearance of concave molecules, spher- ical particles and associates of various shapes and sizes) is provided by electron photomicrographs 73 of dilute solutions of collagen samples subjected to mechanical treatment. Thus, experimental data obtained for collagen indicate that the rupture of covalent bonds in the macromolecule to give free radicals is accompanied by the rupture of weak intermolecular contacts. This results in disordering (loosening) of the protein structure, the change in the macromolecule conformation and in `mechanical' denaturation.At extensive stages of the process, collagen acquires the properties of flexible-chain gelatin;73 in dilute solutions, it forms molecular coils and associates composed of several macromolecules held together by new intermolecular bonds, which arise randomly. A water-insoluble fraction has been found in the samples of globular proteins, trypsin and subtilisin subjected to mechanical dispersion, the proportion of this fraction increasing with an increase in the duration of grinding.71 However, its appearance is not related to covalent cross-linking, because this fraction dissolves on heating. Apparently, dispersion leads to a change in the conformation of the protein molecules, resulting in their association, referred to as `mechanical' denaturation.The conformational changes in trypsin molecules have also been observed by circular dichroism.71 The decrease in the amplitude of the Cotton effect in the 250 ± 310 nm range points to appreciable changes in the tertiary structure of the protein, which affect the local environment of chromophore groups, in particular, tryptophan. 4. The change in the catalytic and biological activity of proteins It has been found 75 ± 77 that on stretching a polyamide thread, the enzyme activity of trypsin or chymotrypsin immobilised on it decreases 3 ± 6-fold. However, after termination of stretching and subsequent relaxation, the enzyme activity is restored, i.e. in this case, reversible deactivation of the enzyme occurs. Thus, by subjecting immobilised enzymes to mechanical treatment, one AMDubinskaya a blog (A0/A A/A0 log (A0/A) A/A0 2.0 1.0 0.8 0.8 0.6 0.6 1.2 0.6 0.4 0.4 0.2 0.2 0.4 0.2 5 10 15 t /min 20 40 60 t /min Figure 11.Kinetics of the decrease in the activity (A) of subtilisin (a) and trypsin (b) during mechanical treatment in a mill at 80 K; A0 is the activity of the enzymes before the treatment.72 can change their conformations and control the catalytic proper- ties.Irreversible inactivation of enzymes was observed upon pressing (pressure 4550 MPa)78 and mechanical grinding of some proteases.71, 72 Experimental data for trypsin and subtilisin are presented in Fig. 11. Apparently, mechanical strain leads to the change in the enzyme conformation and in the microenviron- ment of the active site.It was found that some of the enzyme molecules completely lose their catalytic activity, and some molecules start to `operate' at a lower rate than the molecules of the native enzyme.72 The influence of mechanical treatment on the thymalin � a polypeptide complex with immunomodulating properties � has been studied. 79, 80 After mild mechanical treatment in a mill, the biological activity of the preparation increases in both in vitro and in vivo experiments, which is highly important regarding the increase in its efficiency. The reasons for this phenomenon have not been elucidated yet. VI. Mechanochemical synthesis 1. Solid-phase mechanochemical synthesis The importance of mechanochemical synthesis among other methods of synthesis is constantly increasing. In particular, in recent years, substantial progress has been attained in the solid- phase mechanosynthesis using planetary activator mills and Bridgeman anvils.The first studies along this line were concerned with reactions in polymer ± monomer and polymer ± polymer systems, resulting in modification of the initial macromolecules and formation of block and graft copolymers, which are used successfully for practical purposes. Mechanical treatment of these systems was carried out in masticators, extruders, mills, bending rolls, etc. More detailed description can be found in monographs. 1, 3, 4 In this Section, we summarise the examples of solid-phase mechanochemical synthesis based on low-molecular-mass com- pounds carried out over the last decade.14, 15, 18 ± 20, 36, 81 ± 87 The syntheses were carried out using various equipment ranging from simple mortars to planetary activator mills 8 and the Bridgeman anvils.14 Planetary mills operate in pulse mode; the pressure created by these devices is normally about several Gigapascals.The Bridgeman anvils create a constant stress field with a pressure of up to*10 GPa, and the pressure in specially designed diamond anvils can reach 550 GPa. 31 The role of mechanical treatment is mainly to provide forced transfer of the reacting particles and to ensure their contact, although other mechanisms also contribute to the reactions. It was found14 that the degree of transformation of monomers into polymers in the Bridgeman anvils depends on the angle of rotation of the anvils (Fig.12). Plastic deformation ensures massTransformations of organic compounds under the action of mechanical stress 102 P M0 102 P M0 100 1 8 2 4 50 4 3 0 4 3 2 1 y/ rad Figure 12. Yield of the polymer ÖP=M0Ü vs angle of rotation of the anvils (y ) (2000 MPa, 293 K);14 (1) acrylamide, (2) methacrylamide, (3) maleic anhydride, (4) trioxane (1000 MPa). transfer and mixing of reactants and removes the reaction products from the reaction area. Solid-phase mechanochemical reactions occurring under con- ditions of explosion induced by strong uniaxial compression have been found; 81 the characteristic times of these reactions are only 1075 ± 1077 s.Two mechanisms of mechanochemical reactions are most likely: (1) under the action of mechanical stress, intermixing at the molecular level occurs and (2) the product is formed on the surface of macroscopic reacting species. However, in the case of explosion reactions, the high rates cannot be explained in terms of either of these mechanisms. It has been suggested 82 that an explosive chemical reaction is initiated by a shock wave, which loosens the lattice of reacting particles for the period of the relief of elastic stress and thus makes the system quasi-homogeneous. Several examples of mechanochemical syntheses carried out under various conditions are presented below. Diels ± Alder reaction.The action of shear stress on solid cyclopentadiene and cyclobutadiene (2 ± 5 GPa, *150 K) gives rise to dicyclopentadiene and vinylcyclohexene, respectively.83 Synthesis of amides (acylation). Solid mixtures of aromatic amines with carboxylic acids react (pressure up to 8 GPa, rotation angle of anvils up to 720 8, temperature 200 ± 300 K) to give amides.84 The yields reach 50% or even more; the rates of the transformations are greater than the rates of the same processes in the liquid phase by factors of hundreds of thousands. In the case of ortho-phenylenediamine, cyclisation of the resulting amides yields the corresponding benzoimidazoles. H2NC6H4NH2+RCOOH NH R H2NC6H4NHCOR N The cyclisation is accelerated by mechanical stress to a lesser extent than acylation.Mechanochemical synthesis of phthalylsulfathiazole has been accomplished 18 by combined mechanical treatment of phthalic anhydride and sulfathiazole. O N O+ NH2 NHSO2 S O HO2C N NHC(O) NHSO2 S 647 The product (formed in a nearly quantitative yield) is not contaminated by phthalazoleimide or phthalates, which are normally produced in the liquid-phase synthesis. Generally, phthalic anhydride readily enters into solid-phase mechanochemical reactions. Thus its pressure-initiated reaction with sulfacetamide gives rise to N-phthalylsulfacetamide.85 O CO2H O+NH2COCH2SO3H CONHCOCH2SO3H O It should be noted that reactions with phthalic anhydride do not stop after termination of mechanical treatment.Synthesis of polypeptides. The action of high shearing pressure on amino acids gives peptides. As in the case of amides, the reaction affords predominantly linear products rather than cyclic compounds (dioxopiperazines), which are usually formed in these reactions carried out in solutions and melts.87 Synthesis of metal carboxylates. A mixture of sodium hydro- gen carbonate withtaric acid has been found 88 to react under elevated pressures (1 ± 15 kPa) yielding sodium tartrates NaHCO3+HO2C(CHOH)2CO2H NaO2C(CHOH)2CO2H+H2O+CO2 NaO2C(CHOH)2CO2Na+2H2O+2CO2 The action of high pressure in combination with shear strain under conditions of explosion induces the reactions RCO2K+H2O RCO2H+KOH giving salts of organic acids in 70%± 80% yields.The reaction of sodium carbonate with benzoic or salicylic acids was carried out in a planetary activator mill.89 The process has obvious advantages over the conventional liquid-phase syn- thesis�it occurs over one technological stage instead of standard six or seven stages, does not require the use of water, etc. Halogen exchange RHal0+MHal RHal+MHal0 Hal = Br, I; Hal0 = F, Cl, I;M = Li, Na, K, Cs occurs both with aromatic 20, 21 and aliphatic (R = Me, Et, Prn) compounds.90 Synthesis of organometallic compounds. It has been shown that mechanochemical synthesis of organometallic and coordination compounds is, in principle, possible.91 ± 93 Cyclopentadienyl, dicarbollyl, b-diketonate and other organometallic derivatives were synthesised.2. Mechanosynthesis and nanotechnology One task of molecular nanotechnology, which has been develop- ing successfully over the last 10 ± 15 years, is the assembling of complex chemical structures. It has been shown 31 that a chemical reaction can, in principle, be carried out under conditions when it is controlled by forced mechanical migration of individual react- ing species (atoms, molecules, free radicals). The work on the transfer of species is done by molecular mills and manipulators such as an atomic force microscope (AFM), scanning tunnelling microscope (STM) and some other devices. Using these instru- ments, atoms or molecules can be placed (positioned) into a definite position with respect to each other (with allowance for the distance between them and orientation needed for the reaction to be initiated).For example, AFM permits the surfaces to be positioned in relation to one another with an accuracy of *0.01 nm with a compression force of up to 0.01 nN. STM was used to position xenon atoms (4 K) on the surface of a nickel single crystal, which resulted in the formation of a linear heptamer.94 The capacities and prospects for the development of the `posi-648 tional' mechanosynthesis have been described in detail by Drexler.31 The positional mechanosynthesis is carried out in vacuo and differs substantially from the conventional gas- and liquid-phase syntheses. As for solid-phase reactions, the notion of concentra- tion (the number of molecules of a given type in unit volume) is absolutely inapplicable to this type of mechanosynthesis.A certain role in the positional mechanosynthesis is played by local steric and electronic effects; however, mechanical positioning has the crucial influence on the reaction rate. , Dl 6��=7kT d dF ln kreact T The force F acting on the particles and the `activation' length Dl 6�� are related by the expression 31 where kreact is the rate constant for the reaction. Normally Dl 6��^70.1 nm and possible compression forces reach 5 nN, which corresponds to Ea*300 kJ mol71. More realistic esti- mates of the decrease in the activation energy due to the action of mechanical force are presented in the discussion dealing with the rupture of valence bonds (II.2.a) and free-radical substitution (III.3). Within the one-dimensional model and the theory of tran- react fTST , DU6��4kT err sition state, the condition for the occurrence of a reaction is given by the expression t¡¦ln P where DU6�� is the height of the potential barrier, treact is the time of the reaction, fTST is the frequency factor (for a mechanochemical reaction with a relatively rigidly fixed arrangement of the reacting species, fTST51012 s71) and Perr is the probability of an error in a mechanochemical operation.At 300 K, assuming that treact=1077 s and Perr=10715, DU6��420 kJ mol71. The positional mechanosynthesis has several advantages. Thus, unlike the conventional (diffusion mechanosynthesis), in this case, side reactions can be avoided, which is especially desirable for the synthesis of complex molecules containing a large number of functional groups.In the positional mechanosyn- thesis, non-planned collisions of molecules cannot occur and, hence, undesirable reactions are excluded. However, among other factors, the applicability of this method is restricted by the fact that such mechanosynthetic systems are usually sensitive to thermal destruction; therefore, only reactions proceeding at room temperature, i.e. those having relatively low activation energy, can be carried out by positional mechanosynthesis. Mechanical positioning ensures the transformation of the mechanical energy into chemical energy. It allows one to choose between alternative reaction pathways, to diminish the activation energy and to increase the effective concentration of the reactants because they are placed in the most favourable positions with respect to each other.Presumably,31 positional mechanosynthesis would be used for the construction of complex molecules, for example, diamond-like structures. A number of properties of diamond-like materials (strength, hardness, relatively low specific weight, etc.) permit them to be used in nanomechanical systems in order to perform positional mechanosynthesis of other complex molecules. Diamond-like structures consist of polycyclic organic mole- cules composed of sp3-hybridised carbon atoms.95 Some planes, (110) and (100), contain strained reactive alkene groups, which provide for the ability of diamond-like structures to participate in synthetic transformations.The (111) plane in diamond is usually hydrogenated, which opens up the way for its chemical modifica- tion.One modification route is based on the abstraction of a hydrogen atom, which plays an important role in the synthesis of diamonds.95 The hydrogen abstraction can be achieved by virtue of free radicals of various structures. However, to enable posi- AMDubinskaya tional mechanosynthesis, they should comply with definite requirements, namely, they should (a) have a very high hydrogen affinity, (b) contain no bulky groups in the structure, (c) represent a fragment of a structure that can be attached to theAFMorSTM tip and used as the holder during positioning; (d) possess mechanical and chemical stability during positioning and (e) be readily generated and regenerated.31, 95 Under the action of anisotropic compression forces (*20 GPa) at room temperature, fullerene can be converted into diamonds (see II.1.a); therefore, it might be a suitable substance for positional mechanosynthesis of diamond-like materials.3. Polymerisation The mechanochemical polymerisation was first discovered on grinding of acrylic and methacrylic acid derivatives (acrylamide, methacrylamide and sodium and potassium salts of these acids) in the presence of some salts, metals and oxides, which serve as initiators.1 High pressures (*103 MPa) combined with shear stress induce polymerisation of compounds containing C=C bonds (ethylene, styrene, methylstyrene, etc.), C:C bonds (acetylene derivatives), conjugated double bonds (butadiene, cyclopenta- diene, etc.), aromatic rings (benzene, naphthalene, anthracene, etc.) and heterocycles (pyridine, thiophene, etc.) even at the temperature of liquid nitrogen.14 In principle, high pressures in combination with shear strain can cause reactions that do not occur under ambient conditions.For example, the activation energy for ethylene dimerisation is about 200 kJ mol71; however, under the action of pressure and shear strain, the p bond in the ethylene molecule can be cleaved. The resulting biradical 31 can either dimerise to give cyclobutane or initiate polymerisation.It can also be claimed that the aromatic rings in benzene, pyridine, polynuclear compounds, etc., can be cleaved in a similar way, although real mechanisms of these transformations are rather complex.14 In some cases, mechanical stress sharply accelerates polymer- isation. Thus the rate constants for the mechanically initiatee, acrylamide and other monomers are 2 ¡À 5 orders of magnitude greater than the corresponding con- stants found for these reactions in the liquid phase.14 Several groups of researchers 96 ¡À 99 have discovered polymer- isation of frozen monomers, which occurred at very high rates at low temperatures (477 K). The influence of mechanical stress was found to be the main driving force of these processes.It has been shown 96 that local mechanical treatment (a needle prick) of frozen cyclopentadiene (77 K), prepared by the method of molecular beams, causes its chain polymerisation; similarly, a local treatment with a pin of g-irradiated solid acetaldehyde initiates its cryopolymerisation even at 4.2 K.99 It was shown 99 that the local mechanical action on a frozen sample induces the formation of a primary crack, which initiates spontaneous propagation over the sample of a narrow area densely covered by an extensive network of freshly formed cracks. The chemical reaction occurs on the surface of cracks (or near them) and, in turn, create conditions for further destruction in the neighbouring area of the matrix. The solidity of the sample can be violated, for example, due to the temperature or density gradients, arising during the reaction and creating stresses, which destroy the sample.Thus, the matrix undergoes layer-by-layer dispersion under the influence of the running field of mechanical stress, and the reaction wave propagates spontaneously over the sample. The relationship between the reactivity and mechanical stresses arising in the reaction has been studied by EPR for the unfreezing of organic crystals of diacyl peroxides having been subjected to photolysis at *15 K.100 Radical pairs and CO2 molecules are formed in the system and create a high local pressure. The mechanical stress thus arising relaxes as a result of movement of these molecules towards the surface.Transformations of organic compounds under the action of mechanical stress 4.Formation of molecular complexes Mechanical treatment of two-component systems gives rise to various types of molecular complexes � charge transfer com- plexes, inclusion compounds and complexes formed due to acid ± base interactions, hydrogen bonds or simply van der Waals forces. Complexation of the acid ± base type between phenols and amines has been found for a mixture of hexamethylenetetramine (urotropin) and resorcinol.101, 102 The reaction proceeds both during explosion initiated by compression 101 and under rela- tively mild conditions, namely, in a disintegrator;102 the yields are nearly quantitative in both cases. It has been shown that interpolymer complexes (polymeric compounds stabilised by bonds of the ionic type) can be prepared by mechanochemical synthesis under high pressure combined with shear stress.103 Polymethacrylic acid (polymeric acid) and PMMA or polymethylvinyltetrazole (polymeric base) were used as the initial compounds.Combined mechanical grinding of polyvinylpyrrolidone (PVP) with some additives (Ad) (chloranil, phenothiazine, hydro- quinone, acridine, etc.) gives charge transfer complexes of the n ± p and p ± p types, for example, PVP+Ad7 (with chloranil) or PVP7Ad+ (with phenothiazine).104 The samples obtained upon trituration in a mortar of two substances able to form stable radicals, one of which being an electron donor (D) (phenols, catechols, porphyrins, etc.) and the other being an electron acceptor (A) (e.g., quinones) have been studied by EPR spectroscopy.105 The researchers were able to record theEPR spectra of the primary reaction products, biradical triplet complexes or radical pairs, and secondary products�free radicals. DA D+.A7.(or D.A.) D.+A.. The triplet molecular complexes or radical pairs generated by mechanical treatment are much more stable than those prepared by photolysis of the same donor ± acceptor solid mixtures. Apparently, once formed, they are quickly incorporated into the new crystal lattice arising upon mechanical treatment. Electron transfer has also been detected on exposure of mixtures of organic compounds, electron donors and acceptors, to elastic acoustic waves.106 Yet another example of electron transfer is represented by mechanochemical reactions of peroxyl macroradicals with com- pounds containing a tertiary amino group (phenothiazine and pyrazolone derivatives), which have been studied by EPR.63 ROO.+MeNXY ROO7+MeN+.XY. The reaction occurs during mechanical grinding of a mixture of a polymer (PS, polyvinyl acetate, etc.) and a substance with electron-donating properties. Combined mechanical grinding of a- and b-cyclodextrins with acetylsalicylic, benzoic or p-hydroxybenzoic acid yields inclusion compounds.107 Their formation proceeds via a stage of amorph- isation of polymers and low-molecular-mass crystals followed by dissolution of crystals in the amorphous medium. Hungarian researchers 38 prepared inclusion compounds by grinding g-cyclodextrin with fullerene and thus attained solubilisation of the latter substance.The vast majority of studies dealing with the synthesis of molecular complexes are associated with new methods for the development of drugs aimed at increasing their therapeutic activity, which depends on bioavailability. It is known33, 108 that bioavailability of drugs poorly soluble in water is determined by the rate of dissolution. It was found that combined grinding of drugs with polymers of various structures leads to distribution (to a molecular level) of the drug in the polymer matrix to give molecular complexes (in the literature devoted to the technology of drugs, these systems are normally referred to as solid disper- sions 33).As a rule, this combined grinding makes it possible to increase the solubility and the rate of dissolution of hydrophobic compounds in aqueous media.33, 108, 109 Meanwhile, by appropri- ate selection of the initial pair consisting of a polymeric carrier and a drug, the liberation of the drug from the molecular complex can also be retarded (prolonged-action preparations). Preparations of this type have been obtained, for example, by joint grinding of some substance of the benzimidazole series with microcrystalline cellulose.110 The polymeric matrices used for this purpose are usually natural polymers, namely, cellulose and its derivatives, starch, cyclodextrins, proteins, chitin, chitosan and pectin and some syn- thetic polymers [poly(ethylene oxide) or polyvinylpyrrolidone]. The majority of drugs are low-molecular-mass organic com- pounds containing functional groups capable of forming inter- molecular hydrogen bonds (C=O, OH, NH, etc.).During mechanical grinding of mixtures of drugs with polymers, the intermolecular hydrogen bonds are destroyed and new hydrogen bonds with macromolecules are formed (IR-spectroscopy data 108). Thus the molecules of benzoic, salicylic and acetylsali- cylic acids, hexobarbital, etc. form hydrogen bonds of the C=O_HOR type with cellulose and oligosaccharide mole- cules. Derivatives of barbituric acid form in addition NH_O(H)R bonds with hydroxy groups of polymers. In the inclusion compounds described above, obtained by grinding of cyclodextrins with acetylsalicylic, benzoic and p-hydroxybenzoic acids, hydrogen bonds link the OH groups of cyclodextrin to the C=O groups of acids.The redistribution of hydrogen bonds during grinding of acetylsalicylic acid (Aspirin) with some fillers (cellulose, alu- mina) has been studied fairly comprehensively by IR spectro- scopy.39 Aspirin is responsible for an absorption band with a maximum at 1695 cm71, due to the stretching vibrations of the C=O group in the dimer. Grinding of the sample results in broadening of this band and displacement of the nCO vibration frequency of the dimer to 1700 ± 1710 cm71, indicating the appearance of a monomeric species with an intramolecular hydrogen bond.The conversion of the dimer into the monomer is also confirmed by optical diffuse refection spectra.39 The formation of molecular complexes of Aspirin with fillers (vibra- tion frequency nCO=1749 cm71) was not detected in the study cited, 39 although it had been observreviously.111 Upon grinding of isobutylphenylpropionic acid (iboprufen) with poly(ethylene glycol), hydrogen bonds between the carboxy groups of the acid and the hydroxy groups of the polymer (IR- spectroscopy data) and van der Waals interactions between the polymer molecules and the aromatic rings of iboprufen (electronic absorption and luminescence spectra) were detected.111 54321 12 4 y 20 8 16 Figure 13. X-Ray diffraction patterns of sulfathiazole (1), polyvinylpyr- rolidone (2) and their mixtures (3 ± 5) after mechanical treatment for 3 (3), 6 (4) and 12 min (5).112 649650 c/ mg ml71 20 16 12840 20 Figure 14. Change in the rate of dissolution of griseofulvin after mechan- ical treatment of its mixtures with polymers;109 (1) a mixture of griseofulvin with gelatin without mechanical treatment, (2) gelatin, (3) chitin, (4) polyethylene glycol, (5) chitosan.After grinding of a drug ± polymer mixture, peaks character- istic of the drug usually disappear from the X-ray diffraction patterns (an example is shown in Fig. 13). The initial rate of dissolution of a drug after its combined grinding with polymers can increase by a factor of tens (an example is shown in Fig.14). The increase in the solubility is especially pronounced when the mechanical treatment yields a new polymorphic modification with a higher solubility. For instance, in the case of grinding of sulfathiazole with polyvinyl- pyrrolidone in a planetary mill, the solubility of the drug increases almost 10-fold.112 Thus, the whole set of data described above, both direct (optical spectra) and indirect (the decrease in the melting point and heat of melting, the increase in the solubility and in the rate of dissolution), point to the formation of molecular complexes stabilised mostly by hydrogen bonds. The practical importance of the molecular complexes with drugs (in particular, for increasing the bioavailability of the drug) becomes obvious from the results of bioassays, which are few in number but convincing.33, 108, 113, 114 VII.Conclusion The review shows that mechanical stress induces numerous physical transformations and chemical reactions in organic compounds. They are based on the rupture of bonds, generation of free radicals, decrease in the activation energies of reactions, provision for the transport of reacting species, etc.; in some cases, some of the above-listed processes predominate, while in other cases, they occur and act simultaneously. The practical potential of the mechanochemistry has been appreciated and adopted by investigators engaged in diverse branches of science. Solid-phase mechanochemical syntheses of various compounds have been performed by now.The yields in mechanochemical reactions are sometimes higher than those in similar reactions conducted in the liquid phase. The advantages of mechanochemical synthesis include the possibility of performing it at low or room temperatures, environ- mental cleanness (no solvents are involved) and the simplicity of the process technology. A mechanochemical process carried out in a reactor mill includes three main stages (a) grinding of the material in order to attain the optimum size of particles; (b) mixing of the reactants in order to attain the maximum contact between the particles (c) the reaction itself. At present, all the three stages occur simultaneously in the same device, although they require differ- 54 3 21t/ min 60 40 AMDubinskaya ent levels of delivered energy.Apparently, for industrial imple- mentation of mechanochemical synthesis, it would be expedient to separate the stages, i.e. to carry out each stage of the process in a separate specially designed reactor.115 Mechanochemical methods have been recognised in the technology of drug manufacture and are used to control the rate of drug dissolution and to increase their therapeutic activity. 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ISSN:0036-021X    

出版商:RSC    

年代:1999

数据来源: RSC

摘要:

Russian Chemical Reviews 68 (8) 653 ± 684 (1999) N-Fluoro amines and their analogues as fluorinating reagents in organic synthesis G G Furin, A A Fainzilberg Contents I. Introduction II. Fluorination of organic compounds with neutral reagents (R2NF) III. Highly efficient fluorinating reagents based on heterocyclic compounds containing a fluorine atom at the charged nitrogen atom IV. Some examples of fluorination with inorganic tetrafluoroammonium salts V. On the mechanism of fluorination with N-fluoroamines and their analogues VI. The effect of the solvent in fluorination reactions with N-fluoro amines and their analogues. Comparative reactivities of fluorinating reagents containing the N7F bonds VII. Conclusion Abstract. The data on the synthesis and application in organic synthesis of fluorinating compounds containing N7F bonds are surveyed and systematised.The reagents are classified into two categories, viz., neutral (perfluoro-N-fluoropiperidine, N-fluoro- 2-pyridone, N-fluorosulfonamides, N-fluoro-N-alkylamides, N-fluorobis(trifluoromethyl)sulfonylamine, N-fluorobenzo± 1,3,2-dithiazole 1,1,3,3-tetroxide, N-fluoro sultams) and ionic reagents (N-fluoropyridinium, N-fluoroquinuclidinium and 1-alkyl-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane salts). A comparative analysis of the fluorinating activity of the reagents depending on their structure and the nature of the solvent is carried out taking into account theoretical calculations. The possibility of fluorination of various classes of organic com- pounds is discussed.The mechanisms of fluorination with N7F compounds are analysed using kinetic data. The advantages and disadvantages of N-fluoro amines in comparison with elemental fluorine, xenon difluoride and other fluorinating reagents are considered. The influence of the nature of the solvent on the fluorinating activity of N-fluoro amines and their analogues is discussed. The bibliography includes 245 references. I. Introduction Over almost a century, fluorination of organic and inorganic substrates with elemental fluorine has been used as the basis for the synthesis of fluorine-containing compounds. Fluorine is known to be a highly potent fluorinating reagent. However, being a strong oxidant, fluorine is aggressive against numerous organic substrates and solvents and thus does not manifest the high selectivity required in fine organic synthesis.Other plausible fluorinating reagents, such as xenon difluoride and perchloryl GG Furin Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, prosp. Akad. Lavrent'eva 9, 630090 Novosibirsk, Russian Federation. Fax (7-383) 235 47 47 A A Fainzilberg N D Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky prosp. 47, 117913 Moscow, Russian Federation. Fax (7-095) 135 53 28. Tel. (7-095) 135 63 49 Received 25 February 1999 Uspekhi Khimii 68 (8) 725 ± 759 (1999); translated by R L Birnova #1999 Russian Academy of Sciences and Turpion Ltd UDC 547.241+547.539.15 653 654 665 677 678 679 682 fluoride (FClO3), have not received wide acceptance in fluoroor- ganic chemistry, primarily because of their high cost, although their pilot-plant syntheses have already been carried out.For example, the synthesis of FClO3 is being carried out at the Russian Research Centre `Applied Chemistry'. The situation in this area has changed radically in the past decade. The ever increasing application of fluorine-containing compounds as biologically active compounds (first of all, of medicinal drugs) has given a strong impetus to the synthesis of a wide range of new electrophilic fluorinating reagents (fluorine `carriers'), viz., the so-called N-fluoro reagents and fluoro com- pounds (O-fluoro reagents). Undoubtedly, N-fluoroamines and their analogues belong to the most representative class of fluorine `carriers' as regards their number, previous experience and application.A chemist engaged in synthesis will always be able to select a reagent complementary to the substrate to be fluorinated in its physical and chemical characteristics.1 ±6 N-Fluoro reagents surpass O-fluoro and S-fluoro reagents in stability, reliability, safety, ecological friendliness and handling convenience.7±16 In considering the wealth of knowledge concerning the chem- istry of N-fluoro amines and their analogues, we thought it more reasonable to classify these fluorinating reagents into two groups according to the type of the fluorine ± nitrogen bond in their molecule. The first group includes the so-called neutral com- pounds of the type R2NF, i.e., the reagents in which the fluorine atom is bound to the uncharged nitrogen atom.The second group includes the reagents in which the fluorine atom is bound to the positively charged nitrogen atom. The most popular neutral compounds are perfluoro-N-fluo- ropiperidine, N-fluoro-2-pyridone, N-fluoro carboxamides, N- fluoro sulfonamides, N-fluoro sulfonylamines (including per- fluorinated compounds), N-fluoro(diphenylsulfonyl)amine, N- fluoro alkanesulfonimides, N-fluoro benzenesulfonimide and N- fluoro sultams. The most popular quaternary compounds include N-fluoropyridinium, N-fluoroquinuclidinium and 1-alkyl-4-flu- oro-1,4-diazoniabicyclo[2.2.2]octane salts.Only a few N-fluoro-reagents are commercially available. The data on these compounds are summarised in the review by Lal et al.6G G Furin, A A Fainzilberg 654 is assumed that this reaction gives rise to the stable phenoxyl radical 5.27 II. Fluorination of organic compounds with neutral reagents (R2NF) O O OLi But But But But But 1 + F 5 3 But But But O But But F But 4 Polyfluorinated polyethylene 6 containing perfluoropipe- ridine rings with the N7F bond as substituents also possesses the properties of a fluorinating reagent.27 CF2CF n 6 R FN F F F . F NF, F NF, R=Fluorination of sodium diethyl phenylmalonate with the reagent 6 has been described.27 It should be noted, however, that perfluoropiperidine (1) gives compound 2 in 68% yield.27 NaH, 6 PhCF(COOEt)2 PhCH(COOEt)2 2 (17% ± 23%) All fluorine `carriers' of this class are derivatives of secondary amines and their heterocyclic analogues.The methods of their preparation are based on direct substitution of the hydrogen atom in the amino group, most commonly under the action of elemental fluorine. These reactions are carried out at low temperatures under flow-through or static conditions. To avoid destruction, fluorine is diluted with an inert gas (e.g., to 5%±10% concen- tration at the beginning and to 20%± 50% at the end of the reaction). Preparatively, this method is characterised by simplic- ity; the yields of the target products are close to quantitative, especially when the reaction is performed in the presence of sodium fluoride.Some inorganic materials routinely used for this purpose (e.g., glass, quartz, polymers) are stable under these conditions, which makes it possible to use ordinary chemical equipment in conducting experiments with N-fluoro derivatives both in their synthesis and further use as fluorinating reagents. All N-fluoro reagents are oxidants. Attempts have been undertaken 17 to establish a quantitative correlation between their efficiency as oxidants and fluorinating ability, since it is the liberation of fluorine with the cleavage of a relatively weak N± F bond that is the driving force of both oxidation and fluorination. Numerous studies of the fluorination reaction using N-fluoro- reagents have led to an idea of `pseudo-positive' fluorine as an intermediate.Within the framework of this concept, strong electron-accepting substituents in a molecule of the fluorinating reagent will favour fluorination. This is characteristic of all types of reactions involving N-fluoro reagents, e.g., substitutive fluori- nation, reaction with carbanions, addition to the multiple bond, etc. N,N-Dialkylanilines react with the reagent 1 to give fluori- nated N,N-dialkylanilines.24 However, perfluorotetrahydropyri- dine and its derivatives are by-products of this reaction. NR2 NR2 1. The use of perfluoro-N-fluoropiperidine F F F F + + + N NRPh N NF 1 R=Me, Et. Perfluoro-N-fluoropiperidine (1) was obtained by electrochemical fluorination of pyridine or 2-fluoropyridine.18 ± 20 It is a liquid with a boiling point of 49.5 8C.Compound 1 compares favour- ably with other fluorinating reagents as regards its safety and solubility in organic solvents. The reagent 1 is effective in fluorination of aryl anions, the Grignard reagents, 2-nitropropane sodium salt, diethyl malonate derivatives, etc.21, 22 The initial step of this reaction is electron transfer from the dialkylaniline molecule to perfluoropiperidine. This was con- firmed by identification of the dimethylaniline radical cation using EPR spectroscopy.24 (1) FN 7 F F MeO 2. The use of N-fluoro-2-pyridone A highly efficient fluorinating reagent, N-fluoro-2-pyridone (7), Me2CFNO2+ OMe MeO Me2CNO2 Na+ MeOH, MeONa, 78 8C, 1.5 h (54%) N (76%) was obtained by the reaction of fluorine with 2-trimethyl- silyloxypyridine.28 ± 30 7 1 5% F2 in N2 NH(SiMe3)2 PhCF(COOEt)2 2 (64% ± 76%) PhC(COOEt)2 Na+ THF, 50 8C, 15 min O N O NH NF CFCl3 , OSiMe3 778 8C 7Me3SiF 7 1 7 (63%) EtCF(COOEt)2 (58%) THF, 50 8C, 15 min EtC(COOEt)2 Na+ O O COOEt F 1 COOEt 7 N The reagent 7 fluorodemetallates the Grignard reagents and fluorinates regioselectively sodium salts of diethyl malonate derivatives. It is also used in the synthesis of a-fluoro carbonyl compounds.28 + THF F COOEt Na+ 7 RF RMgBr (56%) (26%) O R=Ph (15%), C8H15 (5%), cyclo-C6H11 (11%).1 F PhMgBr 7 R1CHFCOR2 R1CH CR2 O N PhF+ (45%) Ph N (29%) R1=R2=Ph (11 ± 33%); R17R2=(CH2)4 (36%± 44%).7 RCF(COOEt)2+ NaCR(COOEt)2 ONa N R=Ph (39%), PhCH2 (33%), Me (17%), H (9%). Ph3PF2 was obtained in the reaction with triphenyl- phosphine.23 Phenols and N,N-dialkylanilines are fluorinated with the reagent 1 to give a mixture of ortho- and para-fluoro derivatives.24 ± 26 However, lithium 2,4,6-tri(tert-butyl)phenoxide (3) yields fluorinated dienone 4 under the action of the reagent 1. ItN-Fluoro amines and their analogues as fluorinating reagents in organic synthesis 3. The use of N-fluoro carboxamides and N-fluoro sulfonamides N-Fluoro carboxamides and N-fluoro sulfonamides are obtained by fluorination of the corresponding amides or sulfonamides with elemental fluorine or other fluorinating reagents.Thus fluorina- tion of alkylamides with CF3OF results in the corresponding N-fluoroalkylamides in high yields.31 R1CONFR2+CF2=O+HF R1CONHR2+CF3OF R1 Yield (%) R2 30 Me Me(CH2)16 60 Me 13 4-FC6H4 Me H Me 85 H 71 Direct fluorination of sodium N-(perfluoro-4-pyridyl)tri- fluoroacetamide with elemental fluorine was used to obtain the selective fluorinating reagent, viz., (N-fluoro-N-perfluoro-4-pyr- idyl)trifluoroacetamide (8).32 ± 34 NHCOCF3 NFCOCF3 1) NaH 2) F2, N2 F F N N8 The reagent 8 fluorinates diethyl phenylmalonate (NaH, THF, from 710 to 20 8C) to give the fluoro derivative 6 in 66% yield.32 The reaction with enamines results in the corresponding a- fluoro ketones.32 F O 8 N O CH2Cl2, 20 8C (73%) The reactions with phenol (MeOH, 20 8C) and anisole (MeCN, 20 8C) yield mixtures of ortho- and para-isomers (in 1 : 1 and 7 : 3 ratios, respectively).32 OR OR OR F 8 + F R=H (91%), Me (81%).Fluorination of sulfonamides with F2 in the presence of KF or with a FClO3 ±NaH mixture gives the corresponding N-fluoro derivatives of the type 9 (yield*60%). Fluorination of O-acetyl- N-tosyl- and -N-mesylphenylglycinol gives the corresponding N-fluoro derivatives in 52% and 13% yields, respectively.35, 36 R1R2R3CNHSO2R4 R1R2R3CNFSO2R4 9 R3 R2 R1 R4 Me H CO2Et Bn CO2Et H CH2OAc H CO2 Et H Ph Me Ph Pri Ph 4-MeC6H4 , Me, F3C 4-MeC6H4 4-MeC6H4 4-MeC6H4 , Me, F3C 4-MeC6H4 , Me, F3C Compounds 9 possess fluorinating ability and can be used for the synthesis of a-fluorocarbonyl derivatives from enolates (Table 1).35, 36 Normally, fluorination of N-alkyl(aryl)sulfonamides is per- formed in a CFCl3 ± CHCl3 mixture (1 : 1) using 1%± 5% F2 in N2, MeOF or CF3OF as fluorinating reagents.N-Fluoro sulfona- mides 10a ± g were synthesised in this way.37 ± 47 R1 Compound 10 abcdefg Sulfonamide derivatives are preferably fluorinated as the corresponding salts.48 ± 50 Thus the fluorination of sodium per- fluoro-N-(4-pyridyl)methanesulfonamide with elemental fluorine results in perfluoro-N-fluoro-N-(4-pyridyl)methanesulfonamide (11) in 89% yield.49 F CF3SO2NH2 , MeONa, MeOH THF, 80 8C, 24 h N N-Perfluoroquinolyl-, -isoquinolyl and -naphthylsulfon- amides were also introduced into the reaction.49 It is noteworthy that N-tert-butyl-N-fluoro-p-toluenesulfon- amide 10a can be obtained in 69% yield by fluorination of sodium N-tert-butyl-p-toluenesulfonamide with cesium fluoroxysulfate in MeCN at 0 ± 5 8C.51 Perfluorosuccinimide and -glutarimide react with xenon difluoride to give the corresponding N-fluoro imides 12a,b in good yields.52, 53 The fluorination is performed at 0 ± 20 8C in the absence of the solvent or at 0 8C in dichlorodifluoromethane for 24 h.These compounds represent easily distillable liquids, which are stable upon 24-h storage in quartz glassware under nitrogen. The fluorination of sodium phthalimide with cesium fluoroxysul- fate in acetonitrile gives N-fluorophthalimide in 48% yield.45 O (F2C)n NH O n = 2 (a, 55% ± 65%), 3 (b, 50%± 60%).Satyamurthy et al.54 used the reaction of solutions of lactams with 100% fluorine for the synthesis of N-fluoro lactams 13 labelled with 18F. However, the yields of N-fluoro lactams 13a ± c are rather low. Higher yields could be obtained by fluorination of solutions of lactams in Freon with fluorine diluted with neon.53 F2, N2 R1 SO2NHR2 CFCl3,MeCl 770 8C R2 R1 Me Me Me But Me ButCH2 Me Me Me t H Bu7 CF3SO2N Na+ F MeCN, 735 8C, 6 h N (90%) 0 ±22 8C (F2C)n +XeF2 655 SO2NFR2 10a ± g Yield (%) Ref. 37 37 37 14 59 57 37 47 37 71 37 11 47 7 CF3SO2NF 100% F2 FN11 ONF12a,b O656 Table 1.Fluorination of organic compounds with N-fluorosulfonamides in THF.35, 36 Reaction conditions Fluorinating reagent 9 Substrate base R4 R1 R2 R3 T /8C O Me LDAa KHMDSb LDA Ph H Me Ph H Me Ph H Me 4-MeC6H4 4-MeC6H4 Me 740 to720 740 ± 0 740 ± 0 O Bn LDA LDA Ph H Me Ph H Me 4-MeC6H4 Me 74 to720 740 ± 0 O NaH NaH Ph H Me Ph H Me 4-MeC6H4 Me 0 ± 20 0 CO2Et NaH NaH 4-MeC6H4 Me PhCOCH(Me)CO2Et Ph H Me Ph H Me 00 Pri 20 NaH Pri H CO2 Et Me HC(CN)CO2Me aLDA is lithium diisopropylamide; b Potassium bis(trimethylsilylamide). OMe O O (H2C)n (H2C)n +18F2 NH N18F 13a ± e n Radiochemical yield (%) Yield (%) Compound 13 The data on fluorination of several compounds with substi- tuted N-fluorotoluenesulfonamides 10a, c, d are presented in Table 2.37 abcde 4133424819 1 76 2 61 3 79 4 71 5 33 The halogen atoms in alkenyl iodides can be selectively substituted by the fluorine using N-fluorobenzenesulfonamide, via intermediate lithium derivatives.The yields of the resulting fluorides are rather high, although in some cases alkenes are formed in large amounts. The results of fluorination of alkenyl iodides are presented in Table 3.47 N-Fluorolactams 13 can be used for the synthesis of fluoro derivatives labelled with 18F. They react with the Grignard reagents, however, the yields of the reaction products are low.54 13 R1R2C CR3I RMgBr R18F 13c 13c Ph 13d 4-MeC6H4 1-naphthyl cyclo-C6H11 Ph 19 13a 13b 13c 13c Ph Ph 20 Reagent RYield (%) 1 ± 2 8 19 51 30 (a) ButLi, THF± Et2O±C5H12 (4 : 1 : 1),7120 8C; (b) PhSO2NFBut, from7120 to 20 8C.Controlled fluorination of aromatic compounds and deriva- 4. Fluorinating reagents based on N-fluoro sulfonylamines tives of malonic acid withN-fluoro lactams of the type 13 and with N-fluoro sulfonamides 10 and 11 can be used for the synthesis of aromatic fluoro derivatives and fluorinated malonates. Thus sulfonamide 11 fluorinates sodium diethyl phenylmalo- nate, benzene and anisole (a mixture of ortho- and para-fluoroa- nisoles is formed in 3 : 1 ratio and in 98% yield).49 N-Fluorobenzenesulfonamide reacts with anisole (4 h, 150 8C) to yield a mixture of 57% 2-fluoroanisole and 37% 4-fluoro- anisole.53, 54 7 2 (93%) PhC(COOEt)2Na+ 11 THF, 7108C F N-Fluoro imides have found much wider application in organic synthesis than N-fluoro amides.The methods for preparing N-fluorobis[alkyl(aryl)sulfonyl]amines are based on direct fluori- nation of the corresponding bisalkyl(aryl)sulfonylamines (1% ± 3% F2 in Ar or XeF2). Fluorinated products are obtained in up to 70% yields.55 N-Fluorodisulfonylamines of the type CF3SO2NFSO2R (R is perfluoroalkyl, cycloalkyl, aralkyl or aryl) are obtained by fluori- nation of the corresponding imides with elemental fluorine at 720 8C.56 ± 64 Thus treatment of (CF3SO2)2NH with F2 at 22 8C gives N-fluorobis(trifluoromethylsulfonyl)amine (14a) in 95% yield.N-Fluorodisulfonylamines 14b ± e and imides 15 were synthesised in a similar way.59 11 CDCl3,7196 to 35 8C (88%) The fluorination is performed with elemental fluorine diluted with nitrogen in solvents (CHCl3, CFCl3, HF, fluorohydro- carbons, MeCN) at 80 ± 135 8C in the presence of NaF or CaF2. Reaction product O Me F O Bn F O CO2Et F PhCOCF(Me)CO2Et PhCOCF(Me)CO2Et Pri FC(CN)CO2Me OMe 11 CDCl3, 20 8C, 10 min a R1R2C CR3Li R1R2C CFR3+R1R2C CHR3 G G Furin, A A Fainzilberg Yield (%) Enantio- meric excess (%) 10 46 11 40 46 20 466 34 14 30 206 21 21 1866 6 OMe F+ F bN-Fluoro amines and their analogues as fluorinating reagents in organic synthesis Table 2.Fluorination of organic compounds with N-fluorosulfonamides 10.37 Base Substrate NaH NaH Bun4 N+OH7 PhCH(COOEt)2 MeCH(COOEt)2 PhMgCl Me2CHNO2 OH KH Me O N KH N Cl O Ph KH BunLi PhCOCH2CHMe2 Me(CH2)13MgBr Ph2CHCOOH OMe BunLi COPri KH KH OAc MeLi Me BunLi SO2NHBut Note. A, N-fluoro-N-neopentyl-p-toluenesulfonamide (10c); B, N-tert-butyl-N-fluoro-p-toluenesulfonamide (10a); C, exo-N-fluoro-2-norbornyl-p- toluenesulfonamide (10d). Table 3. Fluorination of alkenyl iodides with N-tert-butyl-N-fluoroben- zenesulfonamide.47 Alkenyl iodide Yield (%) Alkenyl iodide fluor- alk- ene ide PriCH2 15 10 n-C6H13CH=CHI 71 76 PhCH=CHI Pri Prn Prn Et 3 85 I I O Pri(CH2)2 Me 12 75 I Pri(CH2)2 Me 12 75 I Syvret et al.have proposed to use lithium derivatives instead of free imides.62 Solvent Reagent T /8C 20 20 20 720 THF PhMe, THF Et2O PhMe, PhH AABB 20 THF B PhMe, THF B 750 20 778 750 CCC Et2O PhMe, Et2O PhMe, THF 20 PhMe, THF C PhMe, THF C 750 PhMe, THF C 750 PhMe, THF C 720 20 PhMe, THF C R1SO2NHR2 Yield (%) fluor- alk- ene ide SO2NH (F2C)n Et SO2 7 88 R1=CF3: R2=SO2CF3 (a, 95%), SO2C4F9 (b, 96%), SO2C6F13 (c, 93%), Me (d, 11%); R1=C4F9, R2=SO2C6F13 (e, 88%). SO2NF SO2 15 I n=2 (77%), 3 (61%), 4 (86%). 7 83 Bun 8 74 I I N-Fluorobis(methylsulfonyl)amine (16) was obtained in 90% yield by fluorination of bis(methylsulfonyl)amine with elemental fluorine (F2:N2=1 : 9) in acetonitrile in the presence of NaF (740 8C).34 (MeSO2)2NH 80 13 Other N-fluorobis[alkane(arene)sulfone]amides 33, 64, 65 and N-fluorobenzo-1,3,2-dithiazine 1,1,3,3-tetroxide [commonly referred to as N-fluoro-o-benzodisulfonimide (NFOBS)] 66, 67 have been synthesised in a similar way.Water or water ± organic solvent mixtures can be used as a reaction medium.64 The best results are attained through the use of sodium salts of the corresponding sulfonimides.34, 65, 67 657 Yield (%) Reaction product 81 53 50 83 ± 87 PhCF(COOEt)2 MeCF(COOEt)2 PhF Me2CFNO2 OH F 60 Me O N 52 F N Cl O Ph PhCOCHFCHMe2 81 Me(CH2)13F 1569 Ph2CFCOOH OMe 24 F COPriF 81 31 F O F 35 Me SO2NHBut 55 F F2 720 8C R1SO2NFR2 14a ± e F2 (F2C)n 720 8C F2 in N2 (MeSO2)2NF 16658 The reagent 14a obtained by the scheme given below (total yield 76% with respect to trifluoromethanesulfonyl fluoride) is the most reactive among other N-fluorodisulfonylamines.59 This compound has a boiling point at 90 ± 91 8C, is thermally stable, can be stored in glassware and is a highly efficient fluorinating agent which has many applications.The same scheme was used to obtain the reagent 14a labelled with 18F (45% radiochemical yield).68 c a, b d F3CSO2NNaSiMe3 F3CSO2NHNa F3CSO2F e f (F3CSO2)2NH (F3CSO2)2NNa (F3CSO2)2NF 14a (a) NH3 (liquid),778 8C; (b) NaOMe, MeOH (95%); (c) (Me3Si)2NH, D (92%); (d) F3CSO2F, THF, 100 8C, autoclave (98%); (e) H2SO4, sublimation in vacuo (93%); ( f ) 100% F2, metal tube, from7196 to 22 8C (95%).N-Fluorobis(phenylsulfonyl)amine (17) often referred to as N-fluorobenzenesulfonimide was obtained in 70% yield by fluo- rination of bis(phenylsulfonyl)amine with fluorine diluted with nitrogen, in acetonitrile or in a CHCl3 ± CFCl3 mixture in the presence of sodium fluoride at 740 8C.69 ± 71 The structure of compound 17 was confirmed by X-ray diffraction analysis.71 a or b (PhSO2)2NH (PhSO2)2NF 17 (a) 10% F2 in N2, NaF, MeCN,740 8C; (b) 10% F2 in N2, NaF, CHCl37CFCl3 (1 : 1),740 8C. N-Fluorobis(phenylsulfonyl)amine (17) is a white crystalline powder, which is soluble in the majority of organic solvents (ether, THF, CH2Cl2, MeCN, PhMe).It is convenient in handling, non- hygroscopic and storage-stable. This reagent can be used for fluorination of carbanions, enolates and enol esters as well as for the preparation of fluorinated intermediates used in the produc- tion of medicinal drugs. Fluorination of the sodium salt of saccharin 18 with cesium fluoroxysulfate in acetonitrile at 0 ± 5 8C gives the N-fluoro derivative 19 in 69% yield. Treatment of compound 18 with fluorine in methanol at 760 8C (770 8C) gives methyl o-fluoro- sulfonylbenzoate 20 formed by the opening of the heterocycle and the fluoro derivative 19.40 An analogue of compound 19, 3-fluorobenzo-1,2,3-oxathia- zin-4-one 2,2-dioxide (21), is prepared by treatment of sodium salt O O 1) NaOH 2) CsSO3F MeCN, 0 ± 5 8C NF SO2 19 COOMe NH SO2 F2, Ar 18 19+ SO2F MeOH, 760 to770 8C 20 of benzo-1,2,3-oxathiazin-4(3H)-one 2,2-dioxide in acetonitrile with dilute fluorine in the presence of sodium fluoride (740 8C).33, 34, 63 The reagent 21 is a rather stable crystalline compound, which manifests high fluorinating ability and is used for fluorination of various compounds including carbanions, steroids and aromatic compounds.34, 63 Examples of these reac- tions are given in Table 4.Table 4. Fluorination of organic compounds with 3-fluorobenzo-1,2,3- oxathiazin-4-one 2,2-dioxide (21).34 Starting compound PhMgBr PhC7(CO2Et)2Na+ O 7 CO2Et Na+ O CO2Et AcO PhOMe a Sodium bis(trimethylsilyl)amide (NaHMDS) was used to generate the enolates and salts.b The ortho : para ratio is 56 : 44. O NH SO2 O Substituted N-fluoro-1,2,3-oxathiazin-4-one 2,2-dioxides 22a,b are prepared in a similar way.65 O R1 NH SO2 R2 O R1=H,R2=Me (a); R1=Me, R2=Me (b). Treatment of benzo-1,3,2-dithiazole 1,1,3,3-tetroxide (23) with nitrogen-diluted fluorine at 740 8C gives N-fluorobenzo- 1,3,2-dithiazole 1,1,3,3-tetroxide (24)66, 67, 72 as a white crystalline powder. Its structure was confirmed by X-ray diffraction analy- sis.71 SO2 NH SO2 23 (a) 10% F2 in N2, NaF, CFCl3 ± CHCl3,740 8C. Electrophilic fluorination of imines 25a ± c with N-fluoro- bis(trifluoromethylsulfonyl)amine (14a) yields mono- (26a ± e) and difluoroketones (27a ± e); the imine anions were generated by treatment with bases.73 R1CCH2R2 NR3 25a ± c (a) 14a, CH2Cl2, Na2CO3 , 22 8C; (b) H3O+.Direct fluorination of imines with (CF3SO2)2NF (14a) gives a-monofluoro and a,a-difluoro ketones without preliminary gen- eration of anions.74 ± 76 The results of fluorination are listed in Table 5.73 Enamines react in a similar way. Thus 1-morpholino-1- G G Furin, A A Fainzilberg Yield (%) Reaction product Reaction condi- tions a solvent T t /8C /h PhF 20 4 20 4 THF THF 5 PhCF(CO2Et)2 (2) 52 O CO2Et 77 20 0.5 THF F O CO2Et 66 n-C6H14 65 8 F OAc OAc 59 MeCN 20 4 O FOMe 77 b MeCN 150 5 F O NF 1) Na 2) F2, N2, NaF SO2 O 21 (88%) O R1 NF 1) Na 2) 5% F2 in N2, NaF SO2 R2 O 22a,b a SO2 NF SO2 24 (90%) a, b R1CCHFR2 + R1CCF2R2 O 27a ± e O 26a ± eN-Fluoro amines and their analogues as fluorinating reagents in organic synthesis Table 5.Synthesis of fluoro ketones by fluorination of imines 25 with the reagent 14a.73 R3 R2 Yield of Yield of 26 (%) 27 (%) 14a : 25 Ratio Compo- R1 unds 25 ± 27 a H Ph Prnn b 4-MeC6H4 c Ph Me Prnn d 4-MeOC6H4 n e 4-BrC6H4 82 15 83 16 58 17 70 17 78 16 0 330 360 380 260 30 2.4 : 1 1 : 3 H Pr 2.4 : 1 1 : 3 2.4 : 1 1 : 3 H Bu 2.4 : 1 1 : 3 H Bu 2.4 : 1 1 : 3 phenylpropene reacts with compound 14a to give a-fluoro- propiophenone after hydrolysis.Fluorination of imines and enamines with the reagent 14a can be regarded as an alternative route to a-fluoro ketones, which are usually synthesised from the corresponding enolates. Mild reaction conditions and high yields of the final products make this procedure very promising. The reagent 14a proved to be efficient in fluorination of lithium enolates of esters, amides, ketones, b-diketones and b-oxo esters (enolates are prepared by treatment with lithium diisopropylamide in THF). The fluorination is fairly selective at 22 8C and results in monofluoro derivatives.75 1) LDA 2) 14a, THF, 22 8C R1R2CFCOX R1R2CHCOX 1 Yield (%) X R R2 HHMe Et 76 63 71 83 70 222 HOEt Ph Ph Ph H Ph 87 Ph Ph HPh OCH2Ph H OEt OEt OEt OEt NPri NPri NPri Ph Me Me Et HPh 85 70 86 81 The synthesis of a,a-difluoro derivatives requires 2 equiv.of the reagent 14a and more drastic conditions.60, 66, 75 ± 77 The nature of substituents at the carbonyl group of ketones has no appreciable influence on the yields of the monofluorinated derivatives, which are normally high. Esters are also smoothly fluorinated with this reagent (Table 6).76 14a R1COCH(R3)COR2 CH2Cl2, 22 8C R3=H R1COCF(R3)COR2 28 R1COCF2COR2 29 Lithium diethyl 2-nitromalonate is fluorinated with high yield in the treatment with (CF3SO2)2NF (14a) in THF.60, 76 The fluorination of b-diketones, b-oxo esters and b-oxo- amides with the reagent 14a in non-polar solvents results in the formation of a-monofluoro or a,a-difluoro derivatives. Thus ethyl 2-chloroacetoacetate,74 ethyl 2-acetoxyacetoacetate 78 and 3-chloro-2,4-pentanedione 79 are fluorinated with the reagent 14a in chloroform in quantitative yields.Fluorination of benzoyl- acetone in CH2Cl2 gives 90% of 1-benzoyl-1,1-difluoroacetone, whereas in a CH2Cl2±H2O system the monofluoro derivative is obtained in 93% yield (see Table 6).76 Fluorination of a-oxo esters can also occur in the absence of bases. These compounds generate fluoro derivatives with practi- 659 Table 6. Fluorination of 1,3-dicarbonyl compounds [R1COCH(R3)COR2] with the reagent 14a.76 t /h Yield (%) a R2 R1 R3 Reagent : Solvent : substrate ratio 29 28 7 91 7 83 3 5480 90 20 24 96 CH2Cl2 Me Me Me Me Ph Ph Ph Me HHHHHHHH OEt Me 1 : 1 OEt 1 : 1 2 : 1 2 : 1 2 : 1 2 : 1 2 : 1 1.5 : 1 1.5 : 1 1.3 : 1 OMe Hb 1 : 1 OEt CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2±H2O 11 93 24 CH2Cl2±H2O 8 86 CH2Cl2±H2O 11 94 CH2Cl2±H2O 14 91 78 92 53 THF THF Ph b 1 : 1 Me Me Me OEt Me Me OEt OEt p-NO2C6H4 OEt Pri OMe OEt a After separation by chromatography on SiO2.b Sodium enolate was used. cally quantitative yields upon treatment with equimolar amounts of the reagent 14a.74 14a R1R2CFCOCOOR3 R1R2CHCOCOOR3 Yield (%) R3 R2 R1 95 95 Me Et Et H Me MeH Me H 95 4-Substituted N,N-diphenylpyrazolidine-3,5-diones 30a,b are fluorinated with 1 equiv.of the reagent 14a in acetic acid or in CHCl3 to give 4-n-butyl-4-fluoro-1,2-diphenylpyrazolidine-3,5- dione (31a) and 4-fluoro-1,2-diphenyl-4-[(2-phenylsulfin- yl)ethyl]pyrazolidine-3,5-dione (31b).77 O O PhN PhN 14a (CH2)2R (CH2)2R AcOH or CHCl3 PhN PhN F 30a,b O O 31a,b R=Et (a, 95%), SOPh (b, 90%). The fluorination of 2-phenylindane-1,3-dione (32) with the reagent 14a in acetic acid at 20 8C gives 2-fluoro-2-phenylindane- 1,3-dione (33).42 In fluorination of substituted 4-hydroxycouma- rins 34a ± c with the reagent 14a, the fluorine atom also occupies the a-position relative to the carbonyl group to give compounds 35a ± c in high yields.42 O O Ph 14a Ph F CHCl3, 20 8C, 30 min 32 33 (93%) O O R O R HO CH2Ac CH2Ac F 14a CHCl3, H2O, 35 8C, 15 min O O O 35a ± c O 34a ± c R = H (a, 91%), Ph (b, 92%), 4-ClC6H4 (c, 90%).The fluorination of 4-hydroxy-3-(3-oxobutyl)coumarin 34a in a chloroform ± water mixture (5 min, 35 8C) gives the correspond- ing fluoro derivative 35a (which represents a mixture of diastereo- mers) in a quantitative yield.58 3-Fluoro-3-(1-phenyl-3-oxobutyl)-660 2H-benzopyran-2,4-dione and 3-fluoro-3-[1-(4-chlorophenyl)-3- oxobutyl]-2H-benzopyran-2,4-dione are prepared in a similar way. The highly selective fluorination of heterocyclic compounds with the reagent 14a is better carried out in polar solvents, e.g., 2,2,2-trifluoroethanol or nitromethane.73 N-Fluorobis(trifluoromethylsulfonyl)amine (14a) reacts with some activated aromatic compounds such as toluene, anisole and acetanilide, resulting in the ortho- and para-substituted prod- ucts.65 Monofluoro derivatives are predominantly formed at the ArH : 14a ratio of 2 : 1.As for nitrobenzene, chlorobenzene or acetophenone, they cannot be introduced into this reac- tion.59, 65, 69, 70 The reagent 14a is effective in reactions with alkenes to give addition products of fluorine at the multiple bond. If a CH2Cl2 ± acetic acid mixture is used, the latter enters into the reaction to give acetoxy and hydroxyfluoro derivatives (these reactions were described, e.g., with styrene and trans-b-methyl- styrene).80 CH2Cl2 R1R2 Ph Ph 20 8C, 24 h R1 F F 14a C Ph2C R2 Ph2C CHF+Ph2C(OAc)CF2Ph R1=Ph, R2=H CH2Cl2, AcOH 0 8C, 1.5 h 14a The reagent 14a reacts with a,b-unsaturated carbonyl com- pounds in AcOH to give b-acetoxy a-fluoro ketones.80 Ph PhCH CHFCOR CH2Cl2, AcOH COR OAc OMe 69 1 : 1 Ph 58 4 : 6 Me 71 4 : 6 RYield (%) erythro : threo Ratio Uracil does not react with (CF3SO2)2NF (14a) at 22 8C in AcOH, presumably due to its poor solubility, whereas at 45 8C this reaction is completed in 12 h to give a difluoro derivative.80 1,3-Dimethyluracil is much more reactive and gives a difluoro derivative in the reaction with 2 equiv.of (CF3SO2)2NF (14a) at 22 8C (yield 85%); 1 equiv. of the reagent 14a gives 1,3-dimethyl- 5-fluorouracil.80 N-Fluorodisulfonylamine (14a) is effective in fluorination of various steroids.Thus fluorination of estra-1,3,5-trien-3-ols in CHCl3 gives ortho- and para-fluorinated products. If acetic acid is used as a solvent, fluorine selectively occupies the para-position to give 10b-fluoro-1,4-estradien-3-one derivatives in high yields.61 R1 R2R3 14a CHCl3, 20 8C HO F F + + O HO HO F The fluorination of a suspension of 2,4,6-trihydroxy- pyrimidine in acetic acid with 1 equiv. of (CF3SO2)2NF (14a) at room temperature results in a monofluoro derivative, whereas a 5,5-difluoro derivative is obtained in high yield with 2 equiv. of the reagent.77 This method was used for the synthesis of a wide range of fluorinated pyrimidinetriones.77 G G Furin, A A Fainzilberg O O R2 R2 NR N 1 NR N 1 F 14a AcOH 20 8C, 5 min O O O O HN NHH Ph Me 91 H Me Et BunPh OMe Me Et Me Me 83 R1 R2 Yield (%) 88 H90 H91 H90 H89 H92 92 Along with reagent 14a, other N-fluoro imides, e.g., N-fluo- robis(phenylsulfonyl)amine (17) or N-fluorobenzo-1,3,2-dithia- zole 1,1,3,3-tetroxide (24) are used for fluorination of various classes of organic compounds.Some examples are given in Table 7. The reagent 17 is more efficient than the reagent 24 in fluorination of organometallic compounds and highly stabilised anions (see Table 7). Under the action of the reagent 17 (100 8C, 18 h), acetanilide gives a mixture of isomeric fluoroacetanilides, the yields of the ortho- and para-isomers being 25% and 15%, respectively.65 Fluorination of metallated aromatic and heteroar- omatic compounds with the reagent 17, which is accompanied by the formation of ortho-fluoro derivatives, is used in the synthesis of valuable biologically active compounds, e.g., fluoro- and difluoroveratric aldehydes.74, 81, 82 MeO 1) BunLi, THF, 778 8C 2) 17 F MeO CHO MeO MeO F MeO F MeO MeOCHCl2, TiCl4 CH2Cl2, 20 8C, 24 h F F (28%) (57%) Base-catalysed formation of enolates, subsequent complex- ation with boron compounds and fluorination of the latter with the reagent 17 is a novel method for the synthesis of g-fluorinated a,b-unsaturated ketones.83 ± 85 Thus the reaction of the reagent 17 with a carbanion generated from 4,4a,5,6,7,8-hexahydronaphtha- len-2(3H)-one (36) in the presence of triphenylborane gave the fluoro derivative 37.84 1) KH, HMPA 2) Ph3B 3) 17 O O 36 37 (84%) F The enolate prepared from 10-methyl-1(9)-octal-2-one upon treatment with KH in a HMPA±THF mixture in the presence of triphenylborane gives a fluoro derivative with the reagent 17 in the a : b ratio of 1 : 8.6 (yield 84%).85 Yet another example of efficient fluorination with this reagent in the presence of 2-phenylbenzo[1.3.2]dioxaborol is the synthesis of g-fluorinated steroid enones.Thus the fluoro derivative 39 was prepared from compound 38.84 1) KH, HMPA, O BPh O 2) 17 38 O O 39 (62%) FN-Fluoro amines and their analogues as fluorinating reagents in organic synthesis Table 7.Fluorination with the reagents 17 and 24. Substrate OMe NHCOMe Me CONHBut OMe OC(S)NEt2 SOBut SO2NHMe Me SO2But OSiMe3 LiMeLi O O Ph EtCOPh O Me COOMe Ph COOMe COOMe Ph Ph a The ortho : meta : para ratio is 58 : 5 : 37. b The ortho : para ratio is 62 : 38. c The ortho : meta : para ratio is 65 : 7 : 28. d The organolithium derivative was generated previously by treatment with BunLi in THF. e The lithium derivative was generated previously by treatment withLDAin THF. f The potassium derivative was generated previously by treatment with KH in Et2O. g The potassium derivative was generated previously by treatment with KHMDS in THF. The fluorination of lithium enolates of silylated ketones with the reagent 17 gives a-fluoro ketones 40 in high yields. The Reagent Reagent : substrate ratio 22 : 1 1 : 1 17 17 17 2 : 1 17 50 : 1 17 2 : 1 2 : 1 2 : 1 17 24 2 : 1 2 : 1 17 24 24 2 : 1 2 : 1 2 : 1 17 24 17 1 : 1 17 1 : 1.2 17 1 : 3 17 1 : 1.2 17 1 : 1.2 17 1 : 1.15 17 1 : 1.2 17 1 : 1.3 Tempera- Time ture /8C /h 150 100 5 24 18 100 216 100 6± 7 778 d 6± 7 6± 7 778 d 778 d 6± 7 6± 7 740 d 740 d 6± 7 740 d 6± 7 6± 7 778 d 778 d 24 20 20 778 20 105 20 778 e 20 778 e 20 795 e 20 0 f 20 778 g silyl group is eliminated by treatment with ammonium fluo- ride.86 Reaction product OMe F NHCOMe F Me F CONHBut F OMe OC(S)NEt2 F SOBut F SO2NHMe F Me SO2But F O FF MeF O Ph O F MeCHFCOPh O Me F COOMe Ph COOMe F COOMe Ph F Ph 661 Ref.Yield (%) 65 65 100 a 33 a 65 40 b 65 19 c 74 56 74 74 620 74 74 74 70 74 71 74 74 74 30 65 46 65 76 65 40 65 47 65 85 65 50 65 47 65 82662 1) (Me3Si)2NLi NH4F R1CHCOCH2FR2 R1CHCOCH2R2 2) 17 THF SiMe2But SiMe2But R1CH2COCHFR2 40 Yield (%) Configuration of 40 R2 R1 Et Pr Et Et Pr PhCH2 (CH2)3 (CH2)4 SSRRR 97 97 95 99 99 Synthesis of a-fluoro ketones with the reagent 17 has also been described by Padova et al.87 The fluorinating reagent 17 was used for introducing fluorine into a molecule containing an azetidinone fragment.88 Compound 41 is an intermediate in the synthesis of new antibiotics.ButMe2SiO ButMe2SiO H H F H 17, THF, 750 8C O O N N O O SiMe2But SiMe2But 41 (95%) The fluorination of the azetidinone derivative 42 with the reagent 17 results in a mixture of stereoisomeric 3-fluoro- azetidinones 43a,b (yield 70%). The isomer ratio depends on temperature, e.g., at 20 8C the 43a : 43b ratio is 85 : 15, whereas at715 8C it is 95:5.88 F F H H Ac Ac CO2But CO2But Ac CO2But + N N N 17 THF, 1 h PMP O PMP O O PMP 42 43b 43a PMP is polymethylenepyridine. Compound 17 is a very convenient reagent for diastereoselec- tive fluorination of optically active substances. Thus the fluorina- tion of a dianion generated from (7)-methyl 3-benzamido-3- phenylpropionate gives compound 43 with the anti : syn diaster- eomer ratio of 35 : 65.89 PhCONH 1.LDA, THF, 778 8C PhCONH 2. 17, 6 h COOMe COOMe Ph Ph F 43 (82%) Treatment of methyl phenylacetate with N-fluorodi- sulfonylamine 17 in the presence of hexamethyldisilazane in THF (1 h,778 8C) yields methyl difluorophenylacetate.90 Fluorination of alkylphosphonate anions with the reagent 17 results in monofluoro 44 and difluoro derivatives 45.78, 79, 91, 92 1) Pri2 NK, THF RCHFPO(OEt)2+RCF2PO(OEt)2 RCH2PO(OEt)2 45 44 2) 17,790 to778 8C, 1 h Yield of 44 (%) Yield of 45 (%) R 70 66 48 45 H 11 66 Bu MeO 61 54 (CH2)2 NBoc Boc is tert-butoxycarbonyl.G G Furin, A A Fainzilberg Other N-fluorinating agents can also be used for preparing monofluoro derivatives of alkylphosphonates.72, 91 7 24 (EtO)2PCHFCO2Et (EtO)2PCHCO2Et O (78%) O Li+ 7 14a (EtO)2PCHFCN (EtO)2PCHCN O (51%) O Li+ O Sodium enolate obtained by treatment of compound 46 with sodium bis(trimethylsilyl)amide is fluorinated with the reagent 17 to give the monofluoro derivative 47.92 This method was also used for the synthesis of other fluoro derivatives of oxazolidinone.93 O N O O 1) NaN(SiMe3)2, THF, 778 8C 2) 17, THF, 778 8C O 46 Me Ph O O F N O O O 47 (56%) Me O O PhO O Et Et N O N O 1) LDA, THF, 20 min 2) 0 8C, 2.5 h 3) 24 F Me Ph Me Ph [88% (97% de)] Treatment with the reagent 17 of lithium derivatives of functionalised pyrroles 48 prepared from bromides 48 results in the fluoro derivatives 49.94 Br F R1 R1 1) BuLi, THF, 778 8C, 30 min 2) 17, 25 8C, 12 h N N R2 R2 R3 49 (50%) R3 48 R1, R2=Ar, Alk, CN; R3=CH2OEt, SiPr i3 .N-Fluorobenzo-1,3,2-dithiazole 1,1,3,3-tetroxide (24) is effec- tive in fluorination of enolates and carbanions (Table 8).72 It is also used for stereoselective fluorination of chiral lithium eno- lates.66 O O O O R3 R3 1) LDA 2) 24,778 to 0 8C, 20 min N O N O H F R2 R1 R2 R1 de (%)a Yield (%) R3 R2 R1 Bun Ph i But Ph i 97 96 96 97 89 86 Me H Pr Bun Me H Pr But Me Me Ph Ph PhCH2 Ph 88 85 86 80 84 86 a The diastereomer ratio was determined on the basis of GLC and 1H NMR data.Fluorination of 1,3-dicarbonyl compounds with the imide 24 results in a-fluoro derivatives in yields up to 95%.72 The reaction of the imide 24 with anisole results in a mixture of 2-, 3- and 4- fluoroanisoles (total yield *100%, the isomer ratio is 58 : 5 : 39, respectively).N-Fluoro amines and their analogues as fluorinating reagents in organic synthesis Table 8. Fluorination of ketone enolates and carbanions with N-fluoro- benzo-1,3,2-dithiazole 1,1,3,3-tetroxide (24).72 Substrate a OO Me O Me Ph MeCOOMe Ph NSO2Ph N O2S MeO OMe PhMgBr aKHDMS, lithium bis(trimethylsilyl)amide (LiHDMS) and LDA were used to generate enolates and salts. b The fluorinating reagent was added to the enolate at 0 8C with subsequent warming to 20 8C.c After addition of the fluorinating reagent, the mixture was heated to 20 8C. d The fluorinating reagent was added to the enolate at778 8C with subsequent warming to 0 8C. e The substrate was added to the fluorinating reagent at 0 8C. 5. The use of N-fluoro sultams N-Fluoro sultams are obtained in high yields by the reaction of nitrogen-diluted fluorine (10% F2 in N2) with the corresponding sultams or their derivatives (direct fluorination in CHCl3 ± CFCl3 (1 : 1), 1 h, 740 8C, in the presence of NaF powder35, 95 ± 100). N-Fluro sultams are colourless crystalline compounds that are thermally stable and may be stored without decomposition for a sufficiently long period of time.The fluorinating reagents 50a ± d were obtained by fluorina- tion of the corresponding NH derivatives with FClO3.101 Their structure was confirmed by X-ray diffraction analysis.71 O S R=Pri(a), But (b), cyclo-C6H11 (c), Ph (d). Yet another effective fluorinating reagent of this type is N-fluoro-3,3-dimethyl-2,3-dihydro-1,2-benzothiazole 1,1-dioxide (51).98 ± 107 It is prepared using two main approaches, viz., fluori- nation (10% F2 in N2) of N-trimethylsilyl-3,3-dimethyl-2,3-dihy- dro-1,2-benzothiazole 1,1-dioxide (yield 49%105) and direct fluorination of the NH derivative in the presence of NaF. In the latter case, the yield of compound 51 reaches 74%.105 Time /h Reaction product O F 1 b O 2 b Me F O F 2 c Ph Me F 2 b Me Ph COOMe F 4 c NSO2Ph F 2 d N O2S F MeO 4 e OMe PhF 4 e O O O S NF NH FClO3 R R 50a ± d Yield (%) 80 100 87 65 60 ± 65 45 60 80 663 a NSiMe3 SO2 b NH SO2 c NF SO2 51 (a) (Me3Si)2NH, D, 95%; (b) 10% F2 in N2, CFCl3, CHCl3,740 8C, 49%; (c) 10% F2 in N2, NaF, CFCl3, CHCl3,740 8C, 74%.N-Fluoro sultams 52a ± c on the basis of bicyclo[2.2.1]heptane are synthesised in a similar way.95 ± 99 R2 R2 10% F2 in N2, NaF R2 R2 R1 R1 CHCl3, CFCl3, 740 8C, 30 min O2S NF O2S NH 52a ± c Yield (%) Configuration R2 R1 Compound 52 80 (+) Cl HH H (7) 75 Me abc 80 (+) H N-Fluoro-3,3-dimethyl-2,3-dihydro-1,2-benzothiazole 1,1-di- oxide (51) is effective in fluorination of enolates and carbanions generated by strong bases.105 The reaction is carried out in THF and yields a mixture of monofluoro and difluoro ketones (Table 9).O O O a, b R1 R1 + R1 R2 R2 R2 F F F (a) B7, THF, 778 8C; (b) 51, THF, from778 to 20 8C. Table 9. Fluorination of carbonyl compounds with N-fluoro-3,3-di- methyl-2,3-dihydro-1,2-benzothiazole 1,1-dioxide (51).105 Base R2 R1 51 : substrate ratio Mono : di- fluoro Total yield ketone ratio (%) Ph MeO 40 33 36 27 23 95 : 5 >98: 2 70 : 30 53 : 47 64 : 36 (1.3 ± 1.6) : 1 (1.3 ± 1.6) : 1 (1.3 ± 1.6) : 1 (1.3 ± 1.6) : 1 (1.3 ± 1.6) : 1 LDA LiHMDS NaHMDS KHMDS KHMDS 53 2 : 98 (2.6 ± 3.6) : 1 KHMDS Ph MeO Me Ph 53 66 56 49 40 49 97 : 3 95 : 5 78 : 22 >95: 5 50 : 50 65 : 35 1.1 : 1 1.1 : 1 1.1 : 1 1.1 : 1 1.1 : 1 1.1 : 1 LDA LiHMDS NaHMDS NaHMDS KHMDS KHMDS 64 5 : 95 (2.6 ± 3.6) : 1 KHMDS Me Ph <10 58 27 >98: 2 90 : 10 33 : 67 (1.3 ± 1.6) : 1 (1.3 ± 1.6) : 1 (2.6 ± 3.6) : 1 Me PhCH2O LiHMDS KHMDS KHMDS Me NPri2 20 47 42 >98: 2 >98: 2 54 : 46 LDA KDAa KDAa (1.3 ± 1.6) : 1 (1.3 ± 1.6) : 1 (2.6 ± 3.6) : 1 aKDA is potassium diisopropylamide.664 Table 10.Rate constants for fluorination of some organic nucleophiles with the N-fluoro sultam 51.108 Substrate OSiMe3 CO2Et 7 Me K+ CO2Et O7 K+ Me Li MgBr NMe2 Me2N a For the reagent 51, Eo=70.12. b Calculated for the SET process.c The reaction rate is too small to be measured. dNo other reaction products were found. e 62% of naphthalene and 12% of naphthyltetrahydrofuran were isolated. f The fluorinated products were not characterised. Enantioselective fluorination of lithium enolates can be car- ried out using optically active N-fluoro sultams of the type 51.103 OLi R1 R1=Me (80% ee), Et (72% ee), Bn (86% ee); R2=Me, R3=Pri. The rate of this reaction depends on the nature of the metal and the solvent. Thus propiophenone reacts with N-fluoro sultam 51 at 778 8C, its sodium derivative reacts from 760 8C to Table 11. Asymmetric fluorination of enolates with N-fluorosultams 52a,b.95, 96 Substrate O Me MeO O CO2Me MeO O CO2Et PhCH(Me)CO2Et a 0.8 Equiv.of the reagent 52a was used.Solvent T kexp Nu E (see a) /8C /litre mol71 s71 1.6 60 Cl(CH2)2Cl 1076 (see c) 0.34 Et2O 0 >861072 THF 778 70.39 3.261072 THF 775 70.34 1.961072 0 THF, Et2O 70.29 6.861072 MeCN 0 0 1.361073 OLi R2 R3 F NF + R1 SO2 740 8C, whereas the lithium derivative of propiophenone reacts only at temperatures above740 8C. The rate constants of the fluorination of various compounds with the reagent 51 are listed in Table 10.108 N-Fluoro sultams 52a ± c have found application as enantio- selective fluorinating reagents (Table 11).95, 96, 99 The fluorination of enolates was carried out using 1.5 equiv. of the reagents 52a,b. The ratio of enantiomers was determined by NMR spectroscopy with the use of a shift-reagent.95, 96 Solvent Base T /8C Fluorinating reagent 52b 52a 52a a 52a a 52a 52a THF THF THF THF THF THF LDA LDA NaHMDS NaHMDS NaHMDS NaHMDS 778 to 20 778 778 to 0 778 778 to 0 778 52b 52a 52a NaH NaH NaHMDS Et2O Et2O THF 0 to 20 0 to 20 ¡78 to 0 52b 52a NaH NaH Et2O Et2O 0 to 20 ¡78 to 0 52b 52a 52a THF THF THF LDA LDA NaHMDS ¡78 to 20 778 778 Reaction product kcalc b /litre mol71 s71 O 6.3610724 MeC(F)(CO2Et)2 5610715 3610715 1.261077 see e 1.461077 see f 261075 Reaction product O Me F MeO O CO2Me F MeO O CO2Et FMe PhF CO2Et G G Furin, A A Fainzilberg Yield (%) F no reaction 94 O 80 d Me F F 72 d 170 Yield (%) ee (confi- guration) (%) 35 <5 10(S) 49 67(S) 41 65(S) 40 75(R) 40 65(R) 5028 >95 57 25 46 26 63 59 70 34 <10 62 54 35 29 33665 N-Fluoro amines and their analogues as fluorinating reagents in organic synthesisThe range of stable fluorinating reagents on the basis of III. Highly efficient fluorinating reagents based on heterocyclic compounds containing a fluorine atom at the charged nitrogen atom pyridine has been considerably extended 125 ¡À 128 owing to employ- ment of salts (other than triflates) containing non-nucleophilic anions (BF¡¦4 , PF¡¦6 , SbF¡¦6 ) in their synthesis.This method was used for the preparation and characterisation (by 19F NMR) (see Refs 129 ¡À 131) of numerous N-fluoropyridinium salts with different substituents in the pyridine ring and counterions.Thus the fluorination of pyridine with dilute fluorine (F2:N2=1:4) in the presence of trifluoromethanesulfonic acid in MeCN results in N-fluoropyridinium triflate (53a) in 97% yield.131 Other fluorinating reagents, e.g., cesium fluoroxysulfate, can be used instead of fluorine.133 Thus the reaction of pyridine with cesium fluoroxysulfate in acetonitrile (0 ¡À 5 8C) in the presence of NaBF4 results in stable N-fluoropyridinium tetrafluoroborate in 48% yield. 1) CsSO4F 2) NaBF4 Synthesis of fluorinating reagents in which the fluorine atom is bound to the charged nitrogen atom of a heterocycle is one of the most fruitful ideas in the chemistry of organofluorine compounds.Two groups of reagents are mainly used, viz., N-fluoropyridinium and N-fluoroquinuclidinium derivatives. This type of compounds (they are commonly referred to as charged or quaternary) are characterised by high reactivity which surpasses that of neutral reagents of the typeR2NF. The interest in these compounds is also due to the possibility to vary their structures to match a specific synthetic problem. Therefore, these reagents can be used for fluorination of a vast variety of substrates. It is not accidental that only charged fluorine `carriers' have rapidly found industrial application. BF¡¦4+ N 1. Fluorination with N-fluoropyridinium salts FN Internal pyridinium salts 54a ¡À j were synthesised by introduc- tion of sulfo groups into the pyridinium ring.125, 134 ¡À 136 R3 R3 N-Fluoropyridinium salts are structurally the simplest and most readily available fluorine carriers of the type (R3NF)+X7. Direct fluorination of pyridine and its derivatives with nitrogen-diluted fluorine (10% F2 in N2) in CF2 ClCFCl2 results mainly in 2-fluoropyridines.109 R4 R2 R4 R2 10% F2 in N2 10% F2 in N2 + MeCN,720 8C R R R5 N R1 R5 R1 F N N NF 54a ¡À j Yield (%) Reaction product Substrate T /8C R5 Solvent R4 R2 R3 T /8C Yield (%) Compo- R1 und 54 a 88 Me H Me H SO¡¦3 MeCN:H2O 720 (10 : 1) b H Me H H 92 SO¡¦3 MeCN:H2O 720 (10 : 1) H H Et H 720 SO¡¦3 MeCN 4-MeC5H4N 4-EtC5H4N 4-PriC5H4N 4-PhCH2C5H4N 3,5-Me2C5H3N 3,5-Cl2C5H3N 4-AcC5H4N 4-MeOOCC5H4N 725 725 725 7250 2500 79 84 cd H H ButH SO¡¦3 MeCN:H2O 720 (20 : 1) e 65 H Me H H SO¡¦3 MeCN:H2O 720 (10 : 1) H CF3H H SO¡¦3 MeCN H CF3H Cl SO¡¦3 MeCN CF3 H CF3H SO¡¦3 MeCN H H H SO¡¦3 H (CF3)2CHOH 90 88 95 87 74 720 710 74000 fghij H H SO¡¦3 H H (CF3)2CHOH 2-F-4-MeC5H3N 31 2-F-4-EtC5H3N 32 4-F-4-PriC5H3N 47 2-F-4-CH2PhC5H3N 25 2-F-3,5-Me2C5H2N 37 2-F-3,5-Cl2C5H2N 46 2-F-4-AcC5H3N 26 2-F-4-MeOOCC5H3N 61 Earlier studies of Meinert and Cech 110, 111 showed that the fluorination of pyridine with a F2N2 mixture in CFCl3 at780 8C results in a pyridine ¡À fluorine complex, viz., N-fluoropyridinium fluoride. This compound manifests fluorinating activity at low temperatures (particularly, with respect to uracil and some chloro alkenes).It is very unstable and is decomposed explosively at temperatures above72 8C. In practice, fluorination with N-fluo- ropyridinium fluoride can be carried out only at temperatures below720 8C, which restricts the applicability of the method. Attempts to replace the fluoride ion by other, less nucleophilic anions were undertaken aimed at obtaining stable N-fluoro- pyridinium salts. These studies are well documented. Fluorination of pyridine and its derivatives in the presence of trifluoromethanesulfonic acid salts 112 ¡À 122 in aqueous acetoni- trile 123 or in polyfluorinated alcohols 124 results in N-fluoro- pyridinium triflates 53a ¡À h.F2, N2 NaOTf Rn Rn Rn + + N The reaction is normally performed in MeCN; however, polyfluorinated alcohols H(CF2)nCH2OH (n=2, 3, 4) can also be used as solvents. This approach was used to prepare N-fluo- ropyridinium-3-sulfonates (54i,j) (yields 87% and 74%, respec- tively).137, 138 Compounds 54 belong to the most potent fluorinating reagents. After completion of fluorination, the inter- nal salts are converted into pyridinium sulfonates, which are readily soluble in water but poorly soluble in organic solvents, which facilitates the isolation of the target fluorination products and their separation from the products of degradation of the fluorinating reagent.NF F7 NF TfO7 53a ¡À h Rn = H (a, 80%), 2-Me (b, 60%), 2,4,6-Me3 (c, 49%), 3,5-Me2 (d, 73%), 4-NO2 (e, 86%), 3,5-(CF3)2 (f, 68%), 4-CN (g, 94%), 2,6-(COOMe)2 (h, 72%). Umemoto et al.139 ¡À 142 synthesised N,N0-difluorobipyri- dinium salts by fluorination of bipyridine complexes with Lewis or Br��nsted acids with nitrogen-diluted molecular fluorine (10% F2 in N2). The molecule of these salts has two mutually activating cationic centres. FN+ 1) HX, MeCN 2) 10% F2 in N2 2X7 + 720 8C N N NF55a,b X=BF4 (a, 90%), TfO (b, 89%). The salts 53 represent stable crystalline compounds which decompose without explosion only at, and above, melting points. They are soluble in organic solvents and do not react with glass. This class of fluorinating reagent has found wide application, particularly in fluorination of steroids, sugars and other natural compounds.666 1) BF3,MeCN 2) 10% F2 in N2 +NF 2BF¡ N 4 + 720 8C NF N 56 (86%) N N FN+ +NF 2X7 57a,b Yield (%) Reaction conditions Compound 57 2nd step 1st step aba TfOH, MeCN BF3, MeCN LiOTf, MeCN 10% F2 in N2, 20 8C 89 10% F2 in N2, 0 8C 96 10% F2 in N2, 67 CFCl3 , CHCl3, 735 8C The reagents 53, 55 ± 57 differ in their fluorinating ability as can be exemplified in the reactions with 2-acetylcyclohexanone.139 O O O O MeCN, D F 57a 587 56 278 55b 0.1 85 53a 19 79 Fluorinating reagent t /h Yield (%) Compound 55b turned out to be the most reactive among other compounds tested.1,1 0-Difluoro-2,2 0-bipyridinium bis(te- trafluoroborate) (55a) can be regarded as one of the most efficient reagents for industrial manufacture of fluorine-containing com- pounds by virtue of its high reactivity, high (in comparison with other reagents) content of the active fluorine and ease of syn- thesis.139 Bis(tetrafluoroborate) 55a efficiently fluorinates com- pounds containing an active methylene group as well as aromatic and other compounds.140 Some N-fluorinating reagents, e.g., N,N 0-difluoro-2,2 0-bipyr- idinium (55b) and N-methyl-N0-fluoro-4,4 0-bipyridinium (58) bistriflates and N,N 0-difluoro-2,2 0-bipyridinium (57a) bistetra- fluoroborate, proved to be very convenient reagents for fluorina- tion of various types of organic compounds (Tables 12 and 13).142, 143 Table 12.Fluorination of aromatic compounds with N,N 0-difluorobipyridinium derivatives 57b and 58 (in MeCN).142 Substrate Fluorinating reagent T /8C OMe FN+ +NF. 2BF¡420 57b OMe OMe 20 OMe MeO OH + MeN+ NF. 2TfO7 80 58 80 PhOMe OMe 20 OMe 60 The introduction of readily polymerisable groups into the pyridine ring of the reagents 55 ± 57 allows one to obtain polymers with molecular masses above 500 000 Daltons. The latter are used as electrolytes (i.e., as an active cathode mass) in batteries and as solid fluorinating agents.137 Among quaternary (charged) fluorinating reagents, pyri- dinium salts present the greatest interest for investigators; there- fore, the methods for their synthesis are permanently improved and the areas of application are extended.Thus yet another approach to the preparation of fluorinating reagents on the basis of pyridinium salts consists in fluorination of the corresponding N-trimethylsilyl derivatives with fluorine in MeCN. F2, N2 Rn + + MeCN, 740 8C NF SiMe3TfO7 N Rn = H (a, 78%), 3-Cl (i, 79%), 3,5-Cl2 ( j, 55%), 2-CO2Me (k, 69%), 2,3,4,5,6-Cl5 (l, 67%). The fluorination of the pyridine ± BF3 complex with nitrogen- diluted elemental fluorine (20% F2 in N2) in MeCN or CCl4 at room temperature results in the heptafluorodiborate of a pyridine ±N-fluoropyridinium complex (59) rather thanN-fluoro- pyridinium tetrafluoroborate, which is also an efficient fluorinat- ing reagent.115, 118 ± 121 BF3 F2 in N2 .BF3 N N MeCN, H2O (cat) 2,6-Dichloropyridine gives N-fluoro-2,6-dichloropyridinium tetrafluoroborate upon fluorination with elemental fluorine in a BF3±HF±H2O±MeCN system at 715 8C (yield 76%). The effect of temperature on the fluorination of pyridine with elemen- tal fluorine in a CF3SO3H±MeCN system was estimated by Nukui.143 At 720 8C, the yield of N-fluoropyridinium triflate was 92% after 30 days and at 40 8C it was 99%. Polyfluorinated secondary alcohols (RR0CHOH, where R,R0 are C1±C4 fluo- roalkyl) are used as solvents in the synthesis of the salts.134 The fluorinating ability of N-fluoropyridinium salts depends not only on the nature of the substituent in the pyridine ring, but also on the nature of the counterion.The effect of the latter on the efficiency of fluorination of 1-trimethylsilyloxycyclohexene with N-fluoropyridinium salts has been studied by Umemoto et al.134 Reaction products t /h OMe F 20 OMe OMe F 18 OMe MeO F OH 15 15 2- and 4-FC6H4OMe OMe F 15 OMe 20 G G Furin, A A Fainzilberg Rn TfO7 53a,i ± l . . B2F¡7+ N FN 59 Yield (%) 52 61 60 55 40 40N-Fluoro amines and their analogues as fluorinating reagents in organic synthesis Table 13. Fluorination of organic compounds with the reagent 55b (in MeCN).143 Substrate O CO2Et AcCH(Me)CO2Et PhCOCH2COPh a Me (see b) Ph PhOMe OH (see d) 20 OH OH a In the presence of 20 mol.%of TfOH.b The reaction was carried out in AcOH. c The 2-F : 4-F : 2,4-F2 ratio is 6.5 : 4.6 : 1. d The reaction was carried out in HCO2H. e 50 mol.%of NaHCO3. f The a : b ratio is 1 : 1.7. g The a : b ratio is 1 : 1.4. The best results were obtained with N-fluoropyridinium triflates. They manifest high regio- and stereoselectivity in fluorination of aromatic compounds, compounds containing activated methyl- ene groups, the Grignard reagents, sodium salts of CH-acids, vinyl acetates, enolates, alkyl and silyl enol ethers, organic sulfides, enamides, alkenes, etc. +NF X7+ X T /8C 20 20 36 36 36 CF3SO3 BF4 BF4 SbF6 ClO4Some examples of fluorination of organic compounds with N-fluoropyridinium triflates are given in Table 14.144 The regioselective fluorination of enol esters and ethers with N-fluoropyridinium salts leads to a-fluorocarbonyl com- pounds.114 A modified general fluorination procedure has been proposed which consists in the conversion of a carbonyl com- pound into enol trimethylsilyl ether or enol acetate which is subject to fluorination. a-Fluorinated carbonyl compounds are convenient as starting compounds in fine organic syntheses.130, 144 ± 147 Thus the fluori- nation of the silyl ether 60 with the reagent 53a yields a mixture of a- and b-fluoro ketones 61a,b.116, 148 t /h T /8C Yield Substrate (%) Reaction product O boiling 76 8 PhNHCO2Et CO2Et F 8 48 "" 73 10, 76 AcCF(Me)CO2Et PhCOCHFCOPh, PhCOCF2COPh OAc Me 0.25 51 " Ph F AcO 73 c 9 " OMe FF OH 0.15 61 Et3SiO F F O 18 OH F 72 boiling <0.1 OH OH F 10 OH F CH2Cl2 O OSiMe3 F Yield (%) Time/h 87 traces 1 230 7 72 648 19 4NF) at room temperature.141, 149, 150 N-Fluoropyridinium salts containing the BF¡4 , SbF¡6 or PF¡6counterions give 2-fluoropyridines in good yields upon treatment with bases (Et3N, Pri2NH, Py, MeONa, ButOK, MeCOONa, BunOn heating with N-fluoro-2,4,6-trimethylpyridinium triflate (53b) in the presence of NaOH, ethyl 2-oxocyclohexane- carboxylate is converted into ethyl 1-fluoro-2-oxocyclohexane- carboxylate (yield 84%).Five- and seven-membered cyclic fluorinated b-oxo esters are obtained in a similar way.123, 151 (CH2)n n=0±2.Fluoro derivatives witpredetermined position of the fluorine atom can be synthesised using reagents of the type 53 or 54 for fluorination of steroids under various reaction condi- 667 Yield (%) T /8C t /h Reaction product F 48 boiling 48 NHCO2Et 32 F NHCO2Et OAc OAc 82 f 0.15 (see e) 70 O F OAc OAc 0.5 46 g (see e) 20 O F OAc 19 O F (CH2)3Pri+ + CH2Cl2 20 8C F TfO7 N 53a 60 OSiMe3 (CH2)3Pri (CH2)3Pri + O F 61b (27%) O F 61a (16%) F CO2Et CO2Et 1) NaOH 2) 53b 3) H2O O O (CH2)nG G Furin, A A Fainzilberg 668 Table 14. Fluorination of organic compounds with N-fluoropyridinium triflates 53a,b,j,l.144 Yield (%) Reaction product t /h Solvent Substrate T /8C Fluorinating reagent OH 53a 24 100 75 a PhOH CH2Cl2 F b 22 1-naphthol 36 CH2Cl2 17 CH2Cl2 4-NO2C6H4OH 65 65 72 2-fluoro-1-naphthol (A) 56 4-fluoro-1-naphthol (B) 2,2-difluoro-1(2H)naphthalenone (C) 2-F-4-NO2C6H3OH PhCHFCO2Et n-C7H15CHFCOMe PhCHFCO2H 68 20 PhCH=C(OEt)(OSiMe3) CH2 Cl2 20 n-C7H15CH=C(OSiMe3)Me PhCH=C(OSiMe3)2 CH2 Ê l2 CH2Cl2 222 20 20 53b n-C12H25F 7558 73 78 71 c 0.5 0.5 0.1 0.2 0.2 0.2 Et2O THF THF THF THF THF n-C12H25MgCl PhMgCl Na+[CH(CO2Et)2]7 Na+[MeC(CO2Et)2]7 Na+[PhC(CN)2]7 Na+[PhSO2CHCO2Et]7 000000 THF Na+[ClC(CO2Et)2]7 86 88 e 0.2 18 24 0 CH2(COPh)2 (see d) CH2 ClCH2Cl 60 MeCOCH2CO2Et (see d) CH2 ClCH2Cl 60 PhF FCH(CO2Et)2 MeCF(CO2Et)2 PhCF(CN)2 PhSO2CF2CO2Et (D) 53 PhSO2CHFCO2Et (E) ClCF(CO2Et)2 CF2(COPh)2 MeCOCHFCO2Et (F) 81 MeCOCF2CO2Et (G) CHF(CO2Et)2 80 48 CH2(CO2Et)2 (see d) CH2 ClCH2Cl 60 53j 54 f 23 26 CH2ClCH2Cl CH2Cl2 4-ClC6H4OH 2-naphthol 20 20 2-F-4-ClC6H3OH 1-fluoro-2-naphthol (J) 95 1,1-difluoro-2(1H)-naphthalenone (K) 3-F-4-HOC6H3CO2Me 53 40 20 CH2ClCHCl2 4-HOC6H4CO2Me g 53l 48 20 PhNHCOMe CH2Cl2 PhCH=CH2 80 h 80 h 25 trans-PhCH=CHMe PhCH=CHMe (see i ) Ph(Me)C=CH2 2-FC6H4NHCOMe (H) 51 4-FC6H4NHCOMe (I) PhCH(OAc)CH2F 72 PhCH(OAc)CH2F 56 PhCH(OMe)CH2F 54 PhCH(OEt)CH2F 29 PhCH(OAc)CHFMe PhCH(OAc)CHFMe Ph(CH2F)C=CH2 PhC(Me)(OPri )CH2F 70 Ph(CH2F)C=CH2 Me(CH2)5CHFCOMe Me(CH2)5CHFCOMe cyclo-C6H11COCHFMe AcOH AcOSiMe3 MeOSiMe3 EtOSiMe3 AcOH AcOH AcOH PriOH CH2Cl2 CH2Cl2 CH2Cl2 CH2Cl2 1 72 120 4320.3 10.08 0.16 0.08 33 73 42 58 61 Me(CH2)6C(OSiMe3)=CH2 Me(CH2)5CH=C(OSiMe3)Me cyclo-C6H11(OSiMe3)C=CHMe 10 20 20 20 20 20 20 20 20 20 20 20 20 a The ortho:para : meta ratio is 9 : 3 : 1.b The A: B:C ratio is *8 : 2 : 1. c The D: E ratio is *1 : 12. d The fluorination was performed in the presence of 0.4 equiv. of ZnCl2. e The F :G ratio is*6 : 1. f The J :K ratio is*8 : 1. g TheH: I ratio is*1 : 1. h The threo : erythro ratio is 1 : 1. i The trans : cis ratio is 1 : 1. OAc OAc +O O F F tions.130, 144, 146, 147 Oxo steroids are preliminarily converted into O-silyl enol ethers.146, 147 In the case of a,b-unsaturated oxo steroids, these are to be first converted into trimethylsilyl enol ethers.The choice of a fluorinating reagent makes it possible to selectively synthesise a required isomer. Thus the reagent 54a predominantly fluorinates the trimethylsilyl ether 62 at position 6, whereas the reagent 53a leads to 6- and 4-fluoro derivatives in comparable yields. OAc Fluorination of 3,17-diacetoxyandrosta-3,5,16-triene (63a) with N-fluoropyridinium triflate (53a) occurs selectively and yields compound 65 with the fluorine atom in position 6. The corresponding silyl ether 63b is selectively fluorinated into ring D to yield compound 66.100, 117, 152 ± 154 62 Me3SiON-Fluoro amines and their analogues as fluorinating reagents in organic synthesis OR 53a CH2Cl2, 40 8C 63a,b AcO OAc R=Ac 14 h O F 65 (51%)O R=Me3Si 1 h 66 (54%) AcO 3,17b-Diacetoxyandrosta-3,5-diene is converted into a mix- ture of 6a- and 6b-fluoro-17b-acetoxytestosterones (total yield *81%) upon treatment with the reagent 53a in acetic acid (3 h, 77 8C).155 The stereo- and regioselectivity of fluorination of steroids with the reagent 53a have been studied.115, 116, 143 OR2 53a CH2Cl2, 20 8C, 30 min R1 OR2+O O 67a F F R2 R1 Yield (%) (a : b ratio) 67b 67a OEt OAc OSiMe3 270 18 26 (2 : 3) 72 (1 : 2) 41 (1 : 3) HAc SiMe3 N O 46 H 0 The reagent 53b was used for stereoselective introduction of fluorine into the a-position relative to the carbonyl group of compound 68.The ratio of enantiomers 69a,b depends on the size of the substituent R.154, 155 1) LiHMDS 2) 53b OC(O)CH(R)CO2Me CMe2Ph 778 to 20 8C 68 R F + OC(O)C CMe2Ph OC(O)C CMe2Ph CO2Me 69b 69a 69a : 69b ratio Yield (%) R 79 : 21 67 : 33 67 : 33 38 : 62 62 : 38 87 96 95 788 Me Et Pr Bu PhCH2 669 The use of reagents 53a,b is not confined to fluorination reactions; they can also be used in the synthesis of trans-alkenes. Thus treatment of the Wittig reagents with N-fluoropyridinium triflate 53a makes it possible to obtain the corresponding trans- alkenes under mild conditions and in acceptable yields.156 + 7 53a CHR Ph3P THF, H2O 730 to 20 8C, 4 h R+Ph3PO+Ph3P+ + R N TfO7 H R=COOEt (51%), COPh (50%), COMe (44%), 2-NO2C6H4 (47%), 4-NO2C6H4 (55%), 4-MeOC6H4CO (81%), 4-NO2C6H4CO (71%).F The reaction of sulfides 70 with N-fluoro-2,4,6-trimethyl- pyridinium triflate (53b) yields sulfides 71 fluorinated at the methylene group.157 53b CH2Cl2 , 20 8C R1SCHFR2 71 R1SCH2R2 70 Yield (%) t /h R2 R1 Ph 4-ClC6H4 n-C12H25 Me Ph PhCH2 MeO2CCH(NHCOCF3)(CH2)2 8 230.5 7.5 H 4 85 H 8 87 H 17.5 44 CO2Et 46 CO2Me 45 H 77 H 39 OR2 Fluorination of b-oxo acid allyl ester 72 with N-fluoro-2,4,6- trimethylpyridinium triflate (53b) affords the a-fluoro derivative 73 in 84% yield.158 O O F H 67b CO2C3H5 CO2C3H5 1) NaH, THF 2) 53b 73 72 N-Fluoro-3,5-dimethylpyridinium triflate (53c) and other salts with a substituted pyridine ring fluorinate aromatic com- pounds. Thus benzene is fluorinated with N-fluoro-2,6-dimeth- oxycarbonylpyridinium triflate to fluorobenzene (yield 56%); N-(ethoxycarbonyl)aniline gives a mixture of the corresponding 2- and 4-fluoro derivatives (yields 60% and 27%, respectively).Phenylurethane also yields fluorination products in positions 2 (47%) and 4 (32%) of the aromatic ring. The fluorination of anisole results in a mixture of o- and p-fluoroanisoles which points to the electrophilic nature of the fluorination reac- tion.129, 132, 158 ± 161 The value of the electrochemical reducing potential (E cp=70.66 V) of the N-fluoropyridinium cation also indicates that this cation is a strong electrophile.162 F Bockman et al.160 studied fluorination of aromatic com- pounds with 3,5-dichloro-N-fluoropyridinium triflate 53j on irra- diation with UV light.R F F CO2Me 53j, hn + F 53j, hn670 F OMe OMe 53j, hn MeO MeO F 53j, hn N-Fluoropyridinium sulfonates manifest high selectivity in fluorination of activated aromatic compounds. Thus fluorination of phenol, naphthol, O-trimethylsilylphenol and phenylurethane with the reagent 54j results in the predominant formation of the corresponding ortho-isomers: for phenol, the conversion is 88% and the ortho : para ratio is 40 : 1; the ortho : para ratio for O-trimethylsilylphenol is 34 : 1; and 1-naphthol gives 63% of 2-fluoro-1-naphthol.114, 129 Chloro- and bromophenols as well as N-acylhalogenoaniline are fluorinated with N-fluoropyridinium salts with high selectivity to give high yields of ortho-fluorination products.Thus the reaction of 4-chlorophenol with 2-chloro-6-trichloromethyl-N- fluoropyridinium tetrafluoroborate in ClCH2CHCl2 (3 h, 45 8C) gives 4-chloro-2-fluorophenol in 68% yield.162 N-Fluoropyridinium triflates 155, 163, 164 along with acetylhy- pofluorite 165 are used for fluorination of biologically active compounds. Thus a mixture of 2-fluoro-17b-estradiol (74) and 4-fluoro-17b-estradiol (75) (total yield 60%) was obtained by fluorination of 17b-estradiol in CH2Cl2 ±MeCN (9 : 1) (12 h, 20 8C) with the reagent 53j.Estrol upon fluorination withN-fluoropyridinium triflate also yields a mixture of 2- and 4-fluoro derivatives (ratio 2.5 : 1, total yield 78%).155, 164 OH X 74: X = F, Y =H; 75: X = H, Y = F HO 74, 75 Y Fluorination of dopamine derivatives 76a,b and the dopamine analogue 77 with 3,5-dichloro-N-fluoropyridinium triflate (53j) proceeds under mild conditions and results in the corresponding fluoro derivatives 78a,b and 79.163 MeO CH2CHNHCOR 53j CH2Cl2, 35 8C CO2Me MeO 76a,b MeO CH2CHNHCOR CO2Me F MeO 78a,b R=CF3 (a, 20%), Me (b, 30%). CH2CHNHCOMe 53j CH2Cl2, MeCN, 20 8C, 8 h CO2Me HO 77 F CH2CHNHCOMe CO2Me HO 79 (65%) Pentachloro-N-fluoropyridinium triflate (53l) proved to be efficient in fluorination of unsaturated acids containing a phenyl G G Furin, A A Fainzilberg substituent in positions 4 or 5 leading to fluorinated g- and d-lactones.166 Ph Ph R 53l, NaHCO3 O OH R O MeCN, 20 8C, 1 h F O Yield (%) R Diastereomer ratio H 69 (Z)-Et 72 (E)-Et 51 2.1 : 1 1 : 2.4 N,N 0-Difluoro-2,2 0-bipyridinium- (55b) and N,N 0-difluoro- 4,4 0-bipyridinium triflates (57a) react with 2-acetylcyclohexanone in boiling acetonitrile to give 2-acetyl-2-fluorocyclohexanone (yields 85% and 87%, respectively).167 The reagent 57a is more efficient in this case.Treatment withN-fluoropyridinium salts was used for electro- philic fluorination of azulene and its derivatives.168 Relatively low yields of fluorination products (14% ± 40%) are due to side reactions.In addition, a prominent role is played by the solvent. For example, the reaction of azulene with N-fluoro-4-methylpyr- idinium triflate 53b in acetonitrile or CH2Cl2 gives a mixture of mono- (yields 12% and 3%, respectively) and difluoro derivatives (yields 17% and 5%, respectively). In dichloroethane, the yield of the monofluoro derivative is increased to 24%.168 The heptafluoroborate of the N-fluoropyridinium pyridine complex (59) proved to be an excellent fluorinating reagent in the synthesis of monofluoro derivatives of various classes (Table 15).115 The reagent 59 is highly selective; the reactions occur under mild conditions.129, 136 ± 140, 145 More complex compounds can also be subject to selective fluorination without oxidation and decomposition.Highly selec- tive meso-fluorination of porphyrins is effected with 2,6-dichloro- N-fluoro-pyridinium, 3,5-dichloro-N-fluoropyridinium and pen- tachloro-N-fluoropyridinium triflates.153 This reaction is carried out in acetonitrile or hexafluorobenzene as solvents andK2CO3 or SrCO3 as bases. The yield of the fluorinated product is low. For example, the tetrafluoro derivative 80 is obtained in 20% yield on boiling of octaethylporphyrin for 2 days in hexafluorobenzene.153 Salts of N-fluoropyridinium and its derivatives have obvious advantages over other fluorinating reagents. They are stable, transportable and fit for long-term storage without any deterio- ration of their properties; besides, they are explosion-proof and non-toxic.The fluorination is performed under mild conditions and is not accompanied by side reactions, which is especially important for steroids, sugars and other biologically active com- pounds. Et Et Et Et F F N N Et Et Et Et 59 NH NH HN HN Et Et Et Et N N F F Et Et Et Et 80 2. N-Fluoroquinuclidinium and 4-alkyl-1-fluoro-1,4- diazoniabicyclo[2.2.2]octane salts Like N-fluoropyridinium salts, N-fluoroquinuclidinium salts belong to the most efficient fluorinating reagents of the N-fluoro- amine series. The main method for their synthesis is direct fluorination of the corresponding NH-precursors.132, 169 ± 176 N-N-Fluoro amines and their analogues as fluorinating reagents in organic synthesis Table 15.Fluorination with the complex N-fluoropyridinium ± pyridine (59) heptafluorodiborate in MeCN.115 Substrate OSiMe3 Me3SiO OAc AcO NHCOMe AcO O AcO OAc MeO Ac AcO SMe O2N SMe ClOAc OAc AcO But AcNH But a The cis : trans ratio is 3 : 1. b The cis : trans ratio is 4 : 1. Fluoroquinuclidinium fluoride (81a) was obtained in 83% ±89% yield by direct fluorination of quinuclidine with 10% F2 in CFCl3 at 778 8C.169, 171, 175, 176 Later, preparation of N-fluoroquinucli- dinium salts with other counterions was performed by fluorina- tion of quinuclidine in the presence of the corresponding salts (the Umemoto method). With LiOTf, N-fluoroquinuclidinium triflate (81b) was obtained in 88% yield (fluorination in MeCN at 733 8C).The salts 81a,b are non-hygroscopic compounds soluble in water and polar organic solvents;17 they are non-explosive and convenient for experimenting in glassware. The synthetic proce- dure is simple and gives high yields of target products. t /h T /8C 185 48 25 80 40 120 72 18 25 25 80 120 72 10 25 40 80 965 40 80 726 40 80 72 36 40 80 18 25 18 250 118 80 18 80 48 25 X=BF4 (c, 63%), CF3CO2 (d, 72%), n-C3F7CO2 (e, 47%). Reaction product O F O F AcO O F MeO O F SCH2F O2N Cl SCH2F O FO F F But O F But OF2, CFCl3 778 8C 81a (86%) N F2, LiOTf MeCN,733 8C 671 Yield (%) OSiMe3 88 57 96 OAc 82 69 38 O F 82 68 23 O 60 39 O F 99 87 Ac 46 36 45 263761 62 a 93 b NaX MeCN + + F7 X7 FN FN 81c ± e TfOSiMe3 , 7196 to 20 8C TfO7 +FN 81b672 CH2Cl N CH2Cl N + + MX, MeCN CH2Cl2 Cl7 20 8C N N N CH2CF3 N CH2CF3 N + + CF3CH2OTf F2 in N2, LiOTf TfO7 + CH2Cl2, 0 8C MeCN,740 8C N N(97%) NF 85 (87%) + + TfO(CH2)3OTf N N N N 2TfO7 (CH2)3 CH2Cl2, 0 8C (94%) M=Li, Na; X=TfO (a), BF4 (b).fluorination 1-alkyl-1-azonia-4-azabicyc- of The lo[2.2.2]octane salts with elemental fluorine in the presence of alkali metal salts gives 4-alkyl-1-fluoro-1,4-diazoniabicyc- lo[2.2.2]octanes. Thus treatment of a mixture of 1-methyl-1- azonia-4-azabicyclo[2.2.2]octane (82a) and lithium triflate with elemental fluorine in acetonitrile (3 h,735 8C) leads to 1-fluoro- 4-methyl-1,4-diazoniabicyclo[2.2.2]octane triflate (83a) in 88%± 94% yield.167, 176 ± 182 The tetrafluoroborate 83b is prepared in a similar way.Me N Me N N + + F2 in N2, MX MeCl, MX 2X7 X7 + MeCN,740 8C MeCN, 20 8C N FN N 82a,b 83a,b M=Li, Na. Yield of 83 (%) Yield of 82 (%) Compounds 82, 83 X ab 84 94 86 98 TfO BF41,4-Diazabicyclo[2.2.2]octane N-oxide can also be used as a starting compound. Its reaction with elemental fluorine in aceto- nitrile in the presence of BF3 . Et2Oor HBF4 at 0 8C results in 75% of N-hydroxy-1-azonia-4-azabicyclo[2.2.2]octane tetrafluorobo- rate.183 The N-fluoro derivatives 84a,b and 85 containing one fluorine atom and the bisfluoro derivative 86 have been synthesised in which two bicyclic fragments are linked through a trimethylene bridge (Scheme 1).182 ± 187 The structure of some of these salts has been confirmed by X-ray diffraction analysis.Thus the length of the N7F bond in compounds 84a and 84b is 1.406 and 1.37(2) A, respectively.185 Preparation of 1-fluoro-1,4-diazoniabicyclo[2.2.2]octanes 87 containing various functional groups at the second nitrogen atom involved treatment of 1,4-diazabicyclo[2.2.2]octane with reagents XY containing the corresponding functional group X and a good leaving group Y. In intermediates 88, the anion Z is substituted for the leaving group Y. Then the salts 89 are fluorinated with elemental fluorine in inert solvents.183, 188 N XN XN XN+ + + XY Z7 F2 2Z7 Z7 Y7 + 7Y7 N N N FN 89 88 87 X=OH, OR, OCOR, SO3, SO2R, NO2, NO, P(O)(OR)2; Z=FSO3, BF4, PF6, ClO4, RFSO3.The attempts to synthesise 1,4-difluoro-1,4-diazoniabi- cyclo[2.2.2]octane salts have long been unsuccessful. The synthesis of the reagent 90 could be carried out by fluorination of 1,4- diazabicyclo[2.2.2]octane with elemental fluorine in acetonitrile in CH2Cl N+ F2 in N2 2X7 X7 + MeCN, 740 8C FN 84a,b 2TfO7 + + F2 in N2 N FN (CH2)3 MeCN,735 8C 86 (80%) the presence of BF3 and PF5 or in acetone in the presence of BF3.169 Later, polyfluorinated alcohols [e.g., (CF3)2CHOH)] and sulfuric acid were used as fluorination media (yield >80%).Yet another convenient approach to the synthesis of the reagent 90 is the fluorination of the trimethylsilyl derivative 91.179, 180, 182, 187 NN 3 + BF3 F2 NaBF4 3 + F2 2BF3 90 +BF¡ NNBF¡ NNBF¡3 SiMe3 N+ 2TfO7 2Me3SiOTf MeCN +NSiMe3 91 reagents Grignard Reagents of the type 81 efficiently fluorinate carbanions, the com- pounds.17, 166, 169, 175, 181, 182, 188 ± 191 Some examples of fluorina- tion of organic compounds with the reagent 81a are given below:176 7 Me2CNO2Li+ MeOH, 0 8C 7 PhC(COOEt)2Na+ THF, 710 to 20 8C Li F7 + S THF, 750 to 20 8C FN 81a N CH2Cl2,7196 to 20 8C RMgX R=Ph, X=Br (26%); R=cyclo-C6H11, X=Cl (20%). Fluorobenzene is formed in 22% yield upon reaction of the reagent 81a with phenyltrichlorosilane.169 G G Furin, A A Fainzilberg Scheme 1 + + N NF 4TfO7 3 FN BF¡ N + + F2,MeCN 2BF¡ BF¡ 4 4 + + 735 8C FN FN 90 (85%) (67%) F2 90 aromatic and Me2CFNO2 (47%) PhCF(COOEt)2 (56%)F S (10%) O F O (43%) RFN-Fluoro amines and their analogues as fluorinating reagents in organic synthesis PhSiCl3 81a THF, 750 8C PhF 22% Such popular reagents as 1-fluoro-4-methyl-1,4-diazonia- bicyclo[2.2.2]octane bistriflate (83a) and 4-chloro-1-fluoro- methyl-1,4-diazoniabicyclo[2.2.2]octane bistetrafluoroborate (84b) (commercial names, F-TedaBF4 or SelectfluorTM) possess excellent fluorinating properties and physicochemical charac- teristics.177, 178, 189, 192 NHAcF PhNHAc MeOH, 7196 to 20 8C (80%, ortho : para=62 : 38) OH OH F MeOH, 20 8C Me N+ (100%) 2TfO7 + OMe FN 83a F PhOMe MeCN, 40 8C, 13 h 72% (ortho : para=1:1) PhSO2Na MeCN, 20 8C PhSO2F (100%) The reagents 83a,b and 84b are highly efficient reagents for introducing fluorine into steroids, aromatic compounds, CH-a- cids and sulfides containing a-hydrogen atoms.These reactions occur under mild conditions and give high yields of fluorination products.132, 177, 178 As a rule, fluorination of oxo steroids is performed using acetates or trimethylsilyl derivatives of the corresponding enols as substrates.192, 193 The yields and regioselectivity can be rather high.Fluorination of hydrocortisone, prednisolone and other oxo steroids with the reagent 84b gives 6- or 16-monofluoro deriva- tives under extremely mild conditions.132 Reaction of 3,17b-diacetoxyandrosta-3,5-diene with the reagent 84b in a mixture of acetic acid and 1,2-dichloroethane (3 h, 77 8C) yields a mixture of 6a- and 6b-fluoro derivatives in 81% yield. OAc OAc 84b AcO O F The advantages of the reagents 84b over other fluorinating reagents are illustrated in Table 16. Fluorination of D4- and D1,4-3-oxo steroids with the reagent 84b normally gives a mixture of 4- and 6-fluoro derivatives. The presence of a trimethylstannyl group at the multiple bond of the Table 16. Fluorination of 3,17b-diacetoxyandrosta-3,5-diene. t /h Reagent Yield (%) The a : b ratio T /8C 1 1 : 3 1 : 3 3 : 5 1 : 2 1 : 2 2 : 3 58 38 70 61 71 95 20 770 778 778 40 20 FClO3 CF3OF CF3C(O)ONa, F2 MeC(O)OF 53a 84b 0.25 0.25 100.15 673 steroid allows the introduction of fluorine atoms under mild conditions and in a more selective manner.The yields of 4-fluo- roandrost-4-ene-3,17-dione and 17-O-benzoyl-4-fluorotestoster- one prepared by this method are about 50% and the results obtained are not much lower than those obtained with cesium fluoroxysulfate 194 which is potentially explosive.195 Fluorination with the reagent 84b can be used for introducing the isotope 18F into steroids. O O 84b MeCN, 20 8C, 24 h O O (52%) F SnMe3 Fluorodestannylation with reagent 84b is rather widely used in stereospecific syntheses of complex fluoroalkenes.184 84b R1R2C CF2 CHSnBu3 R1R2C MeCN, 80 8C Fluorination of 1-tosylindole 92a with the reagent 84b in MeCN±MeOHleads to 3-fluoro-2-methoxy-1-tosyl-2,3-dihydro- indole 93 in 48% yield.196 The trans-arrangement of the substitu- ents in the reaction product has been confirmed by X-ray diffraction analysis.In this case, the reaction occurs as conjugated vicinal fluoromethoxylation. The substitution of fluorine for the trimethylstannyl group in the derivative 92b occurs under the action of reagent 84b in acetonitrile to give compound 94 in 21% yield.196 F OMe NTs R=H 84b, MeOH, MeCN 93 R NTs R=SnMe3 92a,b F NTs 84b, MeCN 20 8C, 12 h 94 (40%) R = H (a), Me3Sn (b).Some other reactions of this kind are docu- mented.41, 177, 178, 197, 198 The fluorination of ethyl 1-indanone-2-carboxylate and methyl 5,7-difluoro-1-indanone-2-carboxylate with the reagent 84b leads to ethyl 2-fluoro-1-indanone-2-carboxylate (yield 80%) and methyl 2,5,7-trifluoro-1-indanone-2-carboxylate (yield 83%).192 The fluorination of methyl and menthyl 1-tetralone-2-carbox- ylates and 1-indanone-2-carboxylates with the reagent 84b affords the corresponding a-fluoro esters 95 in high yields.199 O O O O OR OR 1) NaH, DMF, 750 to 20 8C 2) 84b F (CH2)n (CH2)n 95 n=0, 1; R=Me, menthyl. The oxidation of hydroxy compounds was studied in order to determine the activity of fluorine in the fluorinating reagents 17, 59 and 84b.It was found 200 that the reagent 84b quantitatively oxidises hydroquinone to p-benzoquinone (2 h, 25 8C). The yield of p-benzoquinone upon treatment with the reagent 17 is low (30%), whereas the reagent 59 does not react with hydroquinone under these conditions. Treatment of acyclic and cyclic 1,3-diketones, b-oxo esters and b-oxo amides with the reagent 84b results in the correspond- ing mono- and difluoro compounds.189, 190 Selective fluorination of b-dicarbonyl compounds with the reagent 84b is used to obtain biologically active compounds.188G G Furin, A A Fainzilberg 674 O O Ph Ph O O 84b (1 equiv.) MeCN, 20 8C, 5 h F (84%) Ph Ph O O Ph Ph Fluorination of unsaturated compounds with the reagent 84b occurs in accordance with the Markownikoff rule.The reaction begins with the addition of the pseudo-positive fluorine to the multiple bond and generation of an intermediate carbocation. Its outcome depends on the presence of other nucleophiles in the system. Thus the tetrafluoroborate 84b reacts with styrene, a-methylstyrene and stilbene in MeCN in the presence of H2O, AcOH and MeOH, which are involved into the reaction.7, 203, 204 F 84b (2 equiv.) MeCN, 20 8C, 192 h O F (78%) O Ph H 84b, NuH Me Me R2F 84b MeCN, 208C F Nu PhR1 H R1 R2 O O MeCN, 20 8C, 19 h Nu R2 R1 (84%) Yield (%) (erythro : threo ratio) O O 84b Ph NMe2 O O F (96%) Ph NMe2 1) NaH 2) 84b, 20 8C, 27 h O O Ph NMe2 84b 40 8C, 27 days (84%) F F 48 98 89 65 66 75 (72 : 28) 86 (69 : 31) 77 (60 : 40) 65 (66 : 34) OH OMe OH OAc FOMe OH OAc F HHHHHPh Ph Ph Ph HMe Me Me Me HHHH As can be seen from the data of Table 17, the rate of Petasis et al.201 have developed a new procedure for the synthesis of alkenyl fluorides 96, substituted alcohols 97 and difluoroalkylamides 98, which is based on fluorination of alke- nylboric acids with the reagent 84b in the presence of boron trifluoride.methoxyfluorination of substituted alkenes increases with a decrease in their ionisation potential which is in favour of the ionic mechanism of the reaction. H H B(OH)2 BF¡3 K+ BF3 H2O R2 R1 R2 R1 84b (1 equiv.) R1CH CFR2 MeCN, 20 8C 96 In the fluorination of phenylacetylenes with the tetrafluoro- borate 84b in aqueous acetonitrile, the addition of fluorine to the triple bond is accompanied by the addition of water.This reaction occurs with high regioselectivity and yields a,a-difluoroketones. It was shown that the nature of the alkyl substituent in phenyl- acetylenes influences only the fluorination rate without any effect on the yield of the final products.197, 198, 205 84b (2 equiv.) 84b H2O, 20 8C R1CH(OH)CF2R2 97 PhC CR PhC(O)CF2R MeCN, H2O, D, 24 h R1CHNHCOR3 84b (2 equiv.) R3CN, 20 8C Yield (%) R krel CF2R2 98 R3 R2 R1 Yield of 98 (%) Yield of 97 (%) Yield of E:Z ratio 96 (%) 36 51 48 51 <0.01 10.63 0.56 HMe But Ph 69 1 : 1 89 H Ph 82 62 68 77 Me Et Me Me 71 58 1 : 1 5.8 : 1 1 : 1 The reagent 84b was also used for fluorination of tertiary alcohols.In this case, substitution of fluorine for the hydrogen atom of the methyl group occurs to give b-fluoroalkanols 101. 4-MeC6H4 HPh H 87 71 58H 67 Me81 Me Ph Bu 4-ClC6H4 Ph 75 Table 17. Relative rates of methoxyfluorination of some alkenes with the reagent 84b in MeCN.203 k a IP /eV Alkene The reaction of the tetrafluoroborate 84b with cyclopentadi- enylthallium affords 5-fluorocyclopentadiene, which was not isolated but its formation was confirmed by identification of cycloaddition products to acrylates 99a,b and dimethyl acetylene- dicarboxylate (100).202 F R1 CH CH R2 R2 99a,b R1 84b F F Tl CO2Me MeO2CC CCO2Me 0.64 0.54 1.00 8.60 0.47 0.63 29.0 27.8 32.2 11.3 2-Phenylprop-1-ene trans-1-Phenylprop-1-ene 1,1-Diphenylethylene 1,1-Diphenylpropene Indene 1,2-Dihydronaphthalene 1-Phenylcycloheptene 3-Phenyl-1H-indene 1,2-Dihydro-4-phenylnaphthalene 1-Phenyl-6,7-benzocyclohept-1-ene CO2Me 100 (35%) 8.40 8.36 8.24 8.14 8.40 8.26 7.92 7.73 7.67 7.91 a Hereinafter k is the relative reaction rate constant with respect to that of 1,1-diphenylethylene.R1=Cl, R2=CN (a, 18%); R1=H,R2=CO2Me (b, 17%).N-Fluoro amines and their analogues as fluorinating reagents in organic synthesis 84b Ar(OH)CRMe Ar(OH)CRCH2F MeCN, D 101 (55% ± 90%) R=Me, Ar 0.Reaction of the reagent 84b with some carboxylic acids can occur as fluorodecarboxylation. The possibility of synthesis of fluoro derivatives from the corresponding carboxylic acids is especially important in the furan and pyrrole series. Until very recently, fluorinated furans and pyrroles were not considered to be readily accessible compounds, although they have always attracted attention as starting compounds for the synthesis of fluorinated analogues of natural bactericides. In this particular case, fluorinated reagents with the N7F bond proved to be more efficient than other reagents, in the first place, the elemental fluorine. For example, the reaction of 3-bromofuran-2-carboxylic acid (102) with the reagent 84a in a biphasic system aqueous CCl4 ±NaHCO3 yields 3-bromo-2-fluorofuran.206 Br Br F COOH 84b CCl4, NaHCO3, H2O 20 8C, 1.5 h O O 102 (27%) Pyrrole-2-carboxylic acids containing electron-donor sub- stituents give the corresponding 2-fluoropyrroles upon treatment with the reagent 84b (yields 32%± 47%). Me Me Me Me F Me Me CO2H 84b CH2Cl2, NaHCO3, H2O, 20 8C, 20 min NH (32%) HN (CH2)2CO2Me (CH2)2CO2Me O O 84b F CO2H HN HN NH NH (37%) CH2Cl2, NaHCO3, H2O, 20 8C Tetronic acid derivatives attract attention in connection with the presence of its fragment in some natural biologically active compounds.Direct fluorination of 2-deoxy-L-ascorbic acid (103) with the reagent 84b afforded only traces of the 2-fluoro derivative 104.207, 208 When the reaction is performed in ethanol, a product of fluorine and the ethoxy group addition to the double bond (compound 105) is formed.Compound 104 could only be obtained by treatment of the bromofluoro derivative 106 with tributyl-tin hydride (yield 49%). O O 84a EtOH, 20 8C, 10 h O F F O RH RH EtOHO105 (67%) O HO 103 O 84a RH NBS EtOH, 20 8C, 10 h EtOH, 20 8C, 10 h Br HO O O O O RH 1) Bun3 SnH 2) HOAc F Br HO RH EtOHO106 (87%) F 104 (49%) OH ; NBS is N-bromosuccinimide. R= HO In the reaction of (7)-menthol with the reagent 84b in acetonitrile, the hydrogen atom at the tertiary exocyclic carbon atom is selectively substituted by fluorine.Presumably, the further 675 course of this reaction involves the substitution of the fluorine atom with participation of the solvent. Subsequent saponification leads to the reaction product 107.209 Me Me Me O OH OH 84b MeCN, D, 16 h NaOH CH2Cl2 , 20 8C, 16 h Pri Me2C +HN Me2CNHCOMe 107 (83%) (50%) Me BF¡4 Fluorination of chiral b-oxo sulfoxides 109 with the com- pound 84b resulted in a mixture of diastereoisomeric a-mono- fluoro chiral compounds 110.210 The formation of a,a- difluorinated products is also possible. F R R 4-MeC6H4 4-MeC6H4 1) NaH, THF 2) 84b, DMF S S O O .. .. O O 110 109 4-pyridyl Me Ph 2-pyridyl CH2F CHF2 CF=CHP- 87 70 90 73 RhConver- 60 48 84 sion (%) Yield (%) 80 23 82 70 19 23 52 Benzene derivatives containing electron-donor substituents are fluorinated with the reagent 84b.7, 147, 188, 198, 199 The fact that fluorine occupies the ortho- or para-position testifies to the electrophilic nature of the reagent.Me Me F PhMe + 84b MeCN, D, 16 h (60%) F (20%) OPh PhOPh OPh + F 84b MeCN, 78 8C, 24 h F (29%) (36%) Fluorination with the reagent 84b can be accompanied by oxidation of functional groups. For example, substituted benzyl alcohols and aromatic aldehydes give the corresponding benzal- dehydes or benzoic acids.211 Polycyclic aromatic compounds (biphenyl, naphthalene, anthracene, phenanthrene) and their derivatives give monofluoro derivatives.174, 198 The fluorination of azulene and its derivatives with the reagent 84b affords a mixture of mono- and difluoro derivatives.212 F F 84b + MeOH, MeCN 20 8C, 5 min F R R R R Yield of the difluoro derivative (%) Yield of the monofluoro derivative (%) 382 H 3427 12 6-Pri 4,6,8-Me3 Regioselective fluorination of anthraquinone derivatives with the reagent 84b presents interest for the synthesis of biologically active compounds.213G G Furin, A A Fainzilberg 676 OMe O MeO 84b MeCN, D, 10 days N-Fluoroquinuclidinium (81c),N-fluoropyridinium (53a) and N-fluoro-2,4,6-trimethylpyridinium (53c) tetrafluoroborates were obtained in sufficiently high yields by fluorination of the corre- sponding bases with the reagent 84b.217 CO2Me O CH2Cl N+ OMe O MeO OMe O MeO N BF¡4 BF¡4 + + F F N MeCN, CH2Cl N + N 53c F + 2BF¡ 20 8C, 30 min 4 CO2Me CO2Me + CH2Cl N+ (2%) (22%) O O N NF BF¡4 BF¡4 + + 84b N FN 81c Reactions of the reagent 84b with uracil, thymidine and nucleosides in the presence of an external nucleophile occur as conjugated addition.Thus 5-fluoro- (111) and 5,5-difluoro-6- hydroxy-5,6-dihydroxyuracils (112) were obtained from uracil.214 O O O F F HN HN HN F + 84b H2O, 90 8C OH O OH O O HN NH NH 112 111 Uracil and thymidine derivatives give compounds 113 in high yields.214 O O R2 R2 HN HN Properties of 1-fluoro-4-hydroxy-1,4-diazoniabicyclo[2.2.2]- octane bistetrafluoroborate (115) (commercial names, NFTh and AccufluorTM) are similar to those of the reagent 84b. This compound fluorinates the same substrates in high yields and with high stereoselectivity.The reagent 115 can be obtained by fluori- nation of 1,4-diazabicyclo[2.2.2]octane N-oxide with elemental fluorine in acetonitrile at 8 8C in the presence of BF3 . Et2O and HBF4 (yield 75%).183, 218 This fluorinates naphthalene to 1- fluoronaphthalene, phenanthrene to 9-fluorophenanthrene and pyrene to 1-fluoropyrene 219 but is less stable. It was shown 206, 220 that the stability of fluorinating reagents in water, acetonitrile, alcohols and aqueous alkali decreases in the following order: 17>84b>115. F Fluorination of unsaturated compounds with the reagent 115 O R3 N O N 84b,MeCN, R3OH AcO AcO O O 80 8C, 2 h in the presence of alcohols occurs as the conjugated vicinal fluoroalkoxylation; the formation of monofluoro derivatives occurs with high regioselectivity (Table 18).221 OH N 113 AcO R1 AcO R1 + 2BF¡4+ Yield of 113 (%) R3 R2 R1 Ph R2 (115) FN R2R3 MeCN, R4OH Ph R1 R4O F R1 R3 80 85 82 HHH OAc OAc OAc OH OMe OAc H Me OH 96 Me2C=CMe2 2 0,3 0,5 0-Tri-O-acetylcytidine is fluorinated in MeCN in the presence of methanol to give the difluoromethoxy derivative Treatment of alkenes with the reagent 115 in acetonitrile results in the corresponding fluorinated amides.222 Me2C(F)CMe2 NHCOMe 114.188, 214, 215 MeCN (93%) NH2 NH2 115 70 8C, 1 ± 24 h F PhCHCH2F N N PhCH CH2 F NHCOMe (79%) 84b, MeCN, MeOH OMe N O N O 80 8C, 2 h AcO AcO O O Table 18.Fluorination of substituted styrenes with the reagent 115.221 k Yield (%) t /min R4 R3 R2 R1 T /8C AcO OAc 114 AcO OAc H H H 90 92 60 60 80 80 HMe <0.001 H H Me 0.89 93 93 90 60 60 60 35 35 35 HMe Ac The reagent 84b is used in iodination of aromatic com- pounds.216 Thus treatment of alkylphenyl ethers and para-sub- stituted anisoles with iodine in the presence of an equimolar amount of the reagent 84b affords monoiodo derivatives in high yields. I2, 84b H H Ph PhOR OR I 1.00 95 95 93 30 30 30 35 35 35 HMe Ac R=Me (89%), PhCH2 (90%), Ph (80%).H Ph Ph I2, 84b OMe R OMe R 2.5 98 97 95 30 30 30 35 35 35 HMe Ac I Ph Ph Ph R=F (87%), Cl (89%), Br (91%), I (88%), Ac (90%), CHO (85%), But (92%). 96 96 60 60 80 80 HMe 0.24N-Fluoro amines and their analogues as fluorinating reagents in organic synthesis Table 19. The stereochemistry of methoxyfluorination of cyclic alkenes with the reagent 115.221 t /min Alkene T /8C 60 35 10 35 Ph (CH2)n n=1 55 30 455 10 n=2 n=3 22 35 35 80 22 35 The stereochemical features of fluoroalkoxylation were studied with cyclic compounds containing a multiple bond as examples (Table 19).221 The bistetrafluoroborate 115 is a highly efficient regioselective reagent for the fluorination of ketones (Table 20).223 Treatment of N-acetylaniline with the reagent 115 leads to a mixture of o- and p-fluoro-N-acetylanilines (67 : 33); 4-tert-butyl- 1-trimethylsilyloxycyclohexene gives a mixture of cis- and trans-4- tert-butyl-2-fluorocyclohexanones (10 : 1), while anisole in aceto- nitrile at 20 8C gives a mixture of o- and p-fluoroanisoles (1 : 2.4) (total yield 83%).Some steroids give monofluoro derivatives under extremely mild conditions.224 ± 226 Table 20. Direct fluorination of ketones with the reagent 115.223 t /h a Substrate O(CH2)n 8888 n=1 n=2 n=3 n=4 n=1 n=2 O (CH2)n 10.5 O 8 O 888 n=1 n=2 n=3 (CH2)n O 2 8 But 5 Me But Bun2 CO 12 10 48 30 12 C6H13COMe PhCOMe PhCOCH2Me PhCOCHMe2 a Reaction conditions: 2 mmol of ketone, 2.2 mmol of the reagent 115 in MeCN (30 ml), 80 8C.b The yield was calculated from the 19F NMR spectroscopy data for a mixture of reaction products prior to workup. The isolated yields are given in parentheses. Yield (%) The syn : anti ratio 60 : 40 92 53 : 47 89 73 : 27 59 : 41 25 : 75 25 : 75 40 : 60 1 : 100 96 96 95 95 97 96 Product Yield (%) b O F (CH2)n 80 (70) 92 (84) 85 (78) 85 (78) F 88 (80) 81 (75) O (CH2)n O F 82 (72) O 95 (88) 95 (88) 90 (82) F (CH2)n O F 91 (81) 86 (78) 33 (23) 88 (80) 83 (74) BunCOCHFPrn C5H11CHFCOMe PhCOCH2F PhCOCHFMe PhCOCFMe2 677 X X 115 15 min O AcO F (89%, a : b=1 : 2.2) X=COCH2OAc.The reactivities of the fluorinating reagents 84b, 115 and N-fluoro-2,6-difluoropyridinium tetrafluoroborate in the fluo- rination of dibenzofuran, diphenyl ether and biphenyl were found to be similar. ortho-Isomers are predominant in the reaction products.174 IV. Some examples of fluorination with inorganic tetrafluoroammonium salts Inorganic tetrafluoroammonium salts (e.g., NF4BF4, NF4SbF6) are formal analogues of organic N-fluoro derivatives. Christe et al.227, 228 showed that NF4BF4 fluorinates benzene and its derivatives in anhydrous HF to give fluorinated products. NO2 NO2 NO2 NF4BF4 F F + HF F Me Me Me Me NF4BF4 F F+ F + HF F The fluorination of nitrobenzene results in substitution of both the hydrogen atoms of the benzene ring (the predominant formation of the meta-isomer testifies to electrophilic substitu- tion) and the nitro group, resulting in fluorobenzene.The reaction of tetrafluorobenzene, pentafluorobenzene and hexafluoroben- zene with NF4BF4 gives perfluorocyclohexadienes, i.e., in this case, fluorine adds to the multiple bonds.227 ± 229 R R F F +NF4BF4 HF 25 8C R=H, F. Among inorganic fluorinating reagents, nitrosyl fluoride is worthy of note. This compound is a low-boiling highly toxic gas, and its application as a fluorinating reagent is very limited. Nitrosyl fluoride was used for fluorination of cholesteryl acetate 116 to give 5a-fluoro-6-nitroimine 117 in high yield. The latter was further converted into the corresponding ketone 118.230 Me FNO Al2O3 CH2Cl2, 0 8C AcO AcO F 116 117 NNO2 Me AcO F 118 O Fluorination of steroidal vinyl fluorides with nitrosyl fluoride leads to a,a-difluoro ketones via the intermediate nitro- imines.231, 232678 Me F Me F F NNO2 Al2O3 FNOO O Me F F O (23%) O Prakash et al.233, 234 proposed to use the Olah reagent (hydro- gen fluoride in pyridine) for the activation of nitrosyl fluoride.This results in a highly active fluorinating reagent which fluo- rinates many organic compounds. Thus the fluorination of ketoximes and thioacetals affords the corresponding gem-difluoro derivatives, while alkynes and alkenes are fluorinated to tetra- fluoro- and trifluoroalkanes in sufficiently high yields.Interest- ingly, fullerene C60 is polyfluorinated with nitrosyl fluoride. Treatment of alkyl phenyl sulfides with this reagent affords products of substitution of the hydrogen atoms of the alkyl group by fluorine atoms.233, 234 V. On the mechanism of fluorination with N-fluoroamines and their analogues The experimental data concerning the use of N-fluoroamines and their analogues in organic synthesis altogether suggest that these compounds are electrophilic fluorinating agents. Inasmuch as the formation of F+ is a thermodynamically very unfavourable process and this species is very unstable and can be detected only by spectral methods in the gas phase, the formation of F+ in fluorination is hardly probable.132, 184 This contradiction has led to an idea of specific polarisation of the N7F bond with the appearance of a partial positive charge on the fluorine atom, i.e., the concept of `pseudo-positive' fluorine.However, the idea that N-fluorinating reagents are the sources of `pseudo-positive' or `electrophilic' fluorine does not contribute any rationale to the real mechanism of fluorination. However, N-fluoro reagents can also be regarded as sources of the fluorine radical the existence of which is established (see Ref. 175). The oxidising properties of N-fluorinating reagents, particularly their ability to displace iodine from inorganic iodides (this reaction is of analytical importance) is attributed to the electrophilic nature of the fluorine radical.As a matter of fact, the mechanistic studies of fluorination available are aimed at establishing whether this occurs as single- electron transfer (SET), nucleophilic substitution at the fluorine atom (SN2) or both. SET R2N F Nu R2N7+NuF R2NF+Nu7 SN2 R2N F Nu In considering the mechanism of fluorination, one should take into account that N-fluorinating reagents comprise two groups of compounds, which differ basically in their structures, viz., R2NF and [R3NF]+A7. In addition, the role of nucleophiles can be played by compounds of various classes (e.g., aromatic, unsatu- rated, organometallic, etc.), whereas the term `fluorination' embraces various types of reactions (substitution, addition, etc.). Hence, all the plausible mechanisms of fluorination can in general be realised.The mechanism established in a specific study may be true only for the particular group of N-fluorinating reagents and substrates and for the particular reaction types that had been studied. G G Furin, A A Fainzilberg Differding et al.106, 108, 235, 236 who studied the fluorination of various substrates with N-fluoro sultam 51 attempted to distin- guish between SN2 and SET mechanisms. To this end, they compared experimental rate constants with those calculated theoretically within the single-electron transfer theory. These calculations were based on the known standard redox potentials, E8, and Marcus rearrangement energies for both reactants. As can be seen from Table 10, the values of experimental constants are by many orders of magnitude higher than might be expected based on the electron transfer concept, i.e., the reaction does not occur as a single-electron transfer.Correspondingly, the SN2 mechanism is realised in this case. The reaction of an ester enolate (derived from citronellate) with N-fluoro reagents leads exclusively to the products of electrophilic fluorination at the carbon atom of the carbanion centre. This finding provides additional support in favour of the SN2 mechanism.108, 235 If the reaction proceeded as a single- electron transfer, the substrate would undergo oxidation with subsequent cyclisation. R SN2 F R 7 + XF R SET XF 7 R R XF H However, there are literature data in favour of the SET mechanism. This process is partly realised in fluorination with XeF2, which is known to react by a radical mechanism.The electrochemical reduction ofN-fluoro sultam 51 results in electron transfer, which is accompanied by simultaneous cleavage of the N7F bond with elimination of the fluoride anion and reduction of the reagent 51 to the radical 119 and further to the amide anion 120.106, 108, 235 e 7 N7 7F7 NF SO2 SO2 N SO2 120 119 51 The electrochemical reduction of N-fluoro sultam 121 con- taining a nitro group in the benzene ring yields a radical anion as an intermediate. e 7 7F7 NF SO2 NF SO2 O2N O2N 121 N SO2 O2N According to Differding et al.,235 this step is characteristic of compounds showing high electron affinity. It should be noted that reactions of N-fluoro sultam 51 with nucleophiles (see Table 10) follow the SN2 mechanism.In studies of photochemical electrophilic fluorination of aromatic compounds 160, 161 it was concluded that the reaction occurs through the initial formation of a donor-acceptor complex, since the UV spectra contain absorption bands characteristic of a charge transfer complex (CTC). hn ArH+ . FPy ArH . FPy+ ArH+FPy+N-Fluoro amines and their analogues as fluorinating reagents in organic synthesis The excitation energy, hnCTC, is correlated with the ionisation potential of the aromatic donor. With a decrease in IP, hnCTC decreases favouring the electron transfer, as a result of which the substrate becomes potentially more reactive in electrophilic fluo- rination where the complex is converted into the final reaction products.A mechanism involving the formation of CTC was also proposed by Des Marteaux et al.80 who studied fluorination with (CF3SO2)2NF (14a). Fluorinating reagent The study into the single-electron transfer mechanism carried out by Umemoto et al. (see Ref. 144) was based primarily on the analysis of the composition of fluorination products. The concept of the single-electron transfer, which implies the formation of the fluorine radical, was used for rationalisation of various fluorina- tion processes, viz., reactions of N-fluoropyridinium salts with anions, neutral substrates, the Grignard reagents, alkenes, aro- matic compounds, etc.According to Umemoto, three different mechanisms can be 51 17 realised in the fluorination of unsaturated compounds, viz., a single-electron transfer, classical electrophilic addition and a purely radical mechanism. +NF In accordance with one of these schemes, the first step of this reaction envisages the formation of a p-complex between the fluorinating reagent and the enol ester/ether. XeF2 Further reactions can follow two different routes, viz., transfer a The figures in parentheses refer to the yields of the isolated compound. of fluorine to the substrate and transfer of the radical R to the pyridinium salt (route a) and the addition of the pyridinium salt to the substrate (route b).F a O+ + RO RO + NR X7 + + F OR b VI. The effect of the solvent in fluorination reactions with N-fluoro amines and their analogues. Comparative reactivities of fluorinating reagents containing the N7F bonds F X7 N F X7 N N+ X7 Fluorination can also occur through the intermediate forma- tion of a radical cation from the unsaturated system and radical anion from the fluorinating reagent. (CF3SO2)2NF7 +(CF3SO2)2NF + 7(CF3SO2)2N7 F F Nu7 Despite the evident role of the medium in fluorination reactions, the data accumulated in this area have not yet been adequately generalised and analysed in the literature. Systematic studies in this field have been undertaken comparatively recently by Solkan and Fainzilberg.237 ± 239 A programme for quantum-chemical calculations aimed at quantitation of various effects of the solvent (the effect of solvation, in particular) on the thermodynamic parameters of the fluorination reaction was elaborated. This programme utilises both the point dipole model and the polarising continuum model in the framework of semi-empirical quantum-chemical methods (MNDO, AM-1, MNDO-PM3).+ Nu The studies 237, 239 were carried out with N-fluoropyridinium salts, which are readily available compounds. Their fluorinating ability varies over a wide range depending on the electronic and steric characteristics of substituents (NO2, SO2F, CF3, CO2Me, F, Cl, Br, Me, CO2H, SO2OH, CO¡2 , SO¡3 ) whose position and number can be varied.Unsubstituted pyridine was selected as a substrate. It should be noted that the experimental data currently available do not contradict these schemes. Thus the regio- and stereoselectivity of alkene fluorination fits well into the mecha- nism of formation of a fluoro carbocation as an intermediate species.7, 79, 175 Alkenes in which the intermediate carbocation cannot be stabilised by substituents (e.g., oct-1-ene or cyclohex- ene) do not react with the fluorinating reagent 84b. As expected, polar solvents that favour the formation of a complex between the substrate and the fluorinating reagent facilitate fluorination. The reaction of N-fluoropyridinium salts with non-substi- tuted pyridine is convenient because it allows comparison of the reactivities of fluorine carriers both with each other and with that of a classical fluorinating reagent such as the N-fluoropyridinium cation.If the enthalpy of the reaction is negative, a given fluorine carrier surpassesN-fluoropyridinium in the fluorinating ability; in the case of positive enthalpy, it is inferior to the latter. The generation of intermediate radical species from fluorinat- ing reagents is confirmed by the formation of products of their reac- tion with the radicals present in the system. The formation of radical anions is confirmed by their capture with 1,4-benzoquinone. The introduction of electron traps suppresses the conversion of alkenes. Thus the conversion of trans-b-methylstilbene in the reaction with (CF3SO2)2NF decreases from 100% to 80% in the presence of 1,4-dinitrobenzene The fluorination of benzyl citronellate (122) with N-fluo- In order to establish the criterion of fluorinating activity (the thermal effect, DH) of an exchange reaction in the gas phase, DH(g), and in polar solvents, DH(s), the authors calculated the corresponding enthalpies of formation of the reactants with account of the solvent effect within the framework of the point rinating reagents gives a mixture of a-mono- (123) and a,a- difluoro derivatives (124), which points to the electrophilic nature of the reagent, whereas the reaction with XeF2 affords the cyclic product 125 typical of radical fluorination (Scheme 2).235 Ph O O 1.KHMDS, THF,778 8C 2. XF,778 to 20 8C 122 Ph O O O O + F F F 124 123 Yield (%) a 124 123 28 (18) 31 (31) 59 (43) 21 (21) 23 (18) 64 (45) CF3SO¡3 3 (3) 11 (10) Xn + Xn + + N N FN 679 Scheme 2 Ph O Ph O + H 125 122 125 <10 (4) 20 (20) 00 13 (6) 0 10 (6) 10 (10) +NF680 Table 21.Thermodynamic parameters of the fluorination of pyridine with N-fluoropyridinium salts.237 Fluorinating reagent NO2 +NF NO2 +NF NO2 NO2 +NF O2N NO2 +NF Me Me +NF Me Me Me +NF Me dipole model [DHf (g) and DHf (s)]. The results of this study are summarised in Table 21.237, 239 An analysis of experimental data 237, 239 and some results presented in Table 21 allow the following conclusions about the role of solvation in fluorination with N-fluoropyridinium salts.1. In strongly polar solvents, the DH(s) values are higher (CO2Me, Cl, Br, Me) or lower (NO2, F, CF3, SO2F) than those in the gas phase. 2. The additivity of the substituent effects holds to consider- able extent. 3. The largest increase in DH in the transition from the gas to the liquid phase is observed for internal N-fluoropyridinium salts containing the CO¡2 and SO ¡3 groups as substituents. In the latter case, the effect is so strong that it can be attributed to the crucial role of solvation in the fluorination reaction. However, the fluorinating ability of N-fluoropyridinium salts containing uncharged substituents in the ring depends on the number of substituents and their electronic effects rather than on the solvation effect.In order to increase the fluorinating activity of a compound containing uncharged substituents up to the level of internal N-fluoropyridinium salts, it is necessary to introduce not less than three electron-accepting nitro groups into the molecule (see Table 21). Hence, the introduction of a substituent able to form an internal salt into N-fluoropyridinium salt and the use of polar solvating solvents is a simpler procedure, which enhances the fluorinating activity of the reagent. Solkan and Fainzilberg 240 have established the activation barriers for the reaction of N-fluoropyridinium salts with pyr- idine. These calculations made it possible to select the most plausible transition states and to calculate the activation energies (Ea) in a highly polar solvent.Comparison of Ea values and enthalpies of fluorination in solutions DH(s) has revealed their nearly linear dependence, e.g., an increase in the heat of reaction by 3 kcal mol71 was accompanied by the decrease in the activa- tion barrier by *1 kcal mol71. Thus, the heats of fluorination reactions can be used in estimation of the corresponding activa- tion energies without determination of the structure of the transition state. Other types of N-fluoro derivatives extensively employed in recent synthetic studies have also been studied.239 The calculations were performed by a semi-empirical quantum-chemical method DH(g) /kcal mol71 16.0 31.9 43.1 72.6 74.9 77.6 DH(s) /kcal mol71 10.6 26.9 36.8 0.4 0.9 0.9 Fluorinating reagent DH(g) /kcal mol71 +NF HO2C +NF HO3S 7 +NF 776.4 OO2S +NF 791.6 SO2O7 7 +NF 779.0 OOC +NF 7101.1 COO7 (MNDO-PM3) using a polarising continuum model.241 The thermal effects of analogous reactions were calculated for com- parative assessment of fluorinating activities of various fluorine carriers in solvents of different polarities. + + + N SO3 NF NF54+ + MeN NF+ N 57 + + MeN +NF + + MeN NF+ + N 83 NF (FSO2)2NF+ + N 14f NF + (CF3SO2)2NF+ 14a N NF The calculation of enthalpies of formation of the reagents and the reaction products in the gas phase [DH(g)] and in solution [DH(s)] is an indispensable step in the calculation of DH.In the latter case, the calculations of the Gibbs energy of solvation were carried out for charged molecules. The results of these studies are summarised in Table 22. As can be seen from these data, the fluorination reactions (1) ± (5) are exothermic even if solvents of medium polarity (e=10) are used. This implies that the reagents 14a,f, 54, 57 and 83 surpass N-fluoropyridinium in fluorinating activity. An increase in the solvent polarity results in manifestation of differ- ence in the behaviour of compounds 14a,f, 54 and 57a, 83. For the G G Furin, A A Fainzilberg DH(s) /kcal mol71 5.8 7.9 7.6 8.1 35.8 24.7 38.9 22.0 (1) + N SO¡3 (2) N+ N MeN (3) + (4) +(FSO2)2N7 (5) +(CF3SO2)2N7N-Fluoro amines and their analogues as fluorinating reagents in organic synthesis Table 22.The thermal effects of fluorination of pyridine [reactions (1) ± (5)] with N-fluoro derivatives in solvents of different polarity.237 Reaction 7DH(s) /kcal mol71 e=10 (1) (2) (3) (4) (5) 714.7 717.6 745.7 714.5 729.7 former two compounds, the thermal effect of fluorination increases with an increase in the dielectric constant of the solvent and decreases for the latter two compounds. Such a behaviour of compounds 57a and 83 seems to be due to their structural features, since both of them are dications. Compounds 83 and 14a were the most reactive among other fluorine carriers tested as can be judged from the thermal effects of the fluorination reaction listed in Tables 21 and 22.However, according to Solkan and Fainzilberg 237, 238 the choice of an `absolute champion' among fluorinating reagents is problematic, since their reactivities depend on reaction conditions, first of all, on the nature and polarity of the solvent. On the whole, the approach to the study of the solvent effects in fluorination reactions 237 ± 240 holds great promise, for the information it provides is comprehensive. This approach makes it possible: (i) to obtain the main thermodynamic characteristics of the fluorination reaction, viz., its thermal effect, which serves as a basis for quantitative evaluation of the fluorinating activity of fluorine carriers in various solvents; (ii) to determine the values of heats of solvation for all reactants (the starting compounds and reaction products); (iii) to perform comparative analysis of heats of reaction in order to evaluate the differences in fluorination rates for various reagents and in different solvents.The use of this Table 23. The values of the redox potential, Eredox, and the half-wave potential, E1/2, for several fluorinating reagents.a Reagent Eredox Cl Cl 70.10 CF3SO¡3FN + (PhSO2)2NF 70.78 70.54 +NF.CF3SO¡3 70.37 70.63 70.65 N + F CF3SO¡3 70.75 NF SO2 O2N 71.21 NF SO2 4-MeC6H4SO2NFMe 72.10 71.44 71.52 O FN a In MeCN relative to the standard calomel electrode. e=30 e=20 724.7 712.2 738.6 723.6 738.4 721.9 713.6 740.4 721.3 736.1 E1/2 +0.38 7 +0.16 7 +0.085 70.21 70.23 70.31 7 70.50 71.30 e=78 727.8 710.4 736.4 726.6 741.2 Ref.243 242 243 242 243 243 243 243 242 243 243 approach which takes account of the contribution of solvation to the thermodynamic mechanism of the fluorination reaction is equally efficient both in predicting the optimum conditions for a reaction (the choice of a fluorinating reagent, solvent, etc.) and in the design of new fluorine carriers. As can be seen from the material presented in this section, taking account of the contribution of the solvent has in fact opened a way to the creation of a versatile scale for quantitation of relative reactivities of N-fluoro derivatives.Estimation of this contribution increases the accuracy of prognosis, for it brings them closer to the real experimental conditions. Evidently, the kinetic estimates are more reliable but the kinetic characteristics can hardly be obtained for all currently known reagents. In this context, a demand arose to elaborate a criterion for estimating fluorinating activity with a relatively simple procedure. Until recently, electrochemical reduction at the N7F bond was in fact the only general approach to the quantitative estima- tion of the fluorinating activity of N-fluoro reagents, the electro- chemical reduction potential being the main criterion. Papers devoted to this problem are scarce, since electrochemical reduc- tion is a methodologically complicated procedure. Therefore, these studies were carried out with a limited number of N-fluoro reagents and the results were poorly reproducible.The values of electrochemical reduction potentials for several N-fluoro reagents are summarised in Table 23.242, 243 Since the values of Eredox are poorly reproducible due to the differences in the experimental protocols of electrochemical studies, their application for quantitative estimation of fluorin- ating activity is problematic. According to Differding and Bers- ier,243 which is analogous (PhSO2)2NF, to N- fluoroquinuclidinium, is one of the most reactive fluorinating reagents of the given series, while Gilicinski et al.,242 assign it to the least reactive reagents, which ranks far below N-fluoroquinu- clidinium. It is of note that E1/2 seems to be a more reliable criterion than Eredox. According to recent data,244 in some cases it is difficult to Reagent Eredox O 71.53 NFBut Ph 71.58 O2S NF +0.18 (CF3SO2)2NF FN+ 70.04 +NCH2Cl .2BF¡4 + FN+ 70.04 NMe. 2CF3SO¡3 . Py . B2F¡ + 7 70.34 NF 70.47 +NF.CF3SO¡3 4-MeC6H4SO2NFPrn 72.10 681 Ref. E1/2 243 71.48 243 70.53 242 7 242 7 242 7 242 7 242 7 242 7682 Table 24. Some commercially available N-fluoro reagents. Reagent FFN +N CF3SO2O7 F+N CF3SO2O7 F+NCH2Cl 2BF¡¦4 NF ++NCH2OH 2BF¡¦4 NF + Me SO2NFMe (PhSO2)2NF.B2F¡¦ Py . 7 +NFN+ white 2BF¡¦ crystals +NF aFLCHEMDFluorochem Ltd, Wesley St., Old Glossop, Derbyshire, SK 13 9RY UK; bALD D Aldrich Chemical Company, Milwaukee, WI 53201 USA; cPCR D PCR Inc., Gainesville, FL 32602 USA; d APCI D Air Products and Chemicals Inc., Allentown, PA 18195-1501 USA; eJANCHIM D Janssen Pharmaceuticalaan, 3, 2440 Geel, Belgium; f ALD-SGL D Allied-Signal Inc., Buffalo, NY 14210 USA; g B.p.90 8C (0.01 Torr); h AP-SCDApollo Scientific Ltd, SK4 1RS, Cheshire, UK. determine Eredox with a sufficiently high degree of reliability because of broad maxima on the electrochemical wave curves. Differding and Bersier 243 also hold this viewpoint and offer an original approach to the estimation of the fluorinating ability of N-fluoro reagents. This approach is based on a semi-empirical quantum-chemical calculation of the `reductant couple' (the original term introduced by the authors), DHf (R3N) ¡À DHf (R3N+F7); however, a consistent scale of relative reactivities could be obtained only for structurally related compounds, e.g., of the pyridinium series.245 On the whole, all presently known attempts to create scientific grounds for comparative quantitative assessment of the fluorinat- ing activity of various N-fluoro reagents are represented by the examples described in this section. A wealth of quantitative estimates is scattered over numerous synthetic papers which mainly emphasise the crucial role of the N-fluorinating reagent structure on fluorination.VII. Conclusion The data surveyed in this review demonstrate the intensive development of the chemistry of fluorine carriers in the past Manufacturer Properties state of B.p.M.p. aggregation /8C /8C FLCHEMa 49 liquid 7266 ¡À 268 FLCHEMa 7 white crystalline substance the same 7 185 ¡À 187 ALD,b FLCHEM,a PCRc " 7 234 (dec.) ALO, b APCI, d FLCHEM,a JANCHIMe ALD-SGL f 7 7 50% of reagent on Al2O3 ALD,b PCRc (see g ) 42 ¡À 44 white crystals the same 7 114 ¡À 116 ALD,b PCR,c FLCHEM,a ALD-SGL f 7 dark crystals 196 ¡À 197 ALD,b PCR,c FLCHEM,a ALD-SGL f 166 ¡À 168 AP-SC h 7 4 G G Furin, A A Fainzilberg decades. Fluorination with N-fluoro reagents has stimulated the research in the field of fluorine chemistry as a whole and provided a basis for fine organic synthesis, the synthesis for organofluorine compounds of medicinal purposes, in particular.Atechnology for the production of a series of fluorine carriers has been developed by leading chemical companies of the USA, Great Britain and Japan. 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ISSN:0036-021X    

出版商:RSC    

年代:1999

数据来源: RSC

摘要:

Russian Chemical Reviews 68 (8) 685 ± 696 (1999) New condensation polymers having low dielectric constants A L Rusanov, T A Stadnik, KMuÈ llen Contents I. Introduction II. Factors influencing the dielectric constants of polymers III. Condensation polymers with low dielectric constants IV. Thermostable polymeric foams V. Conclusion Abstract. The review considers factors that determine the dielec- tric properties of the medium as well as the basic approaches to the preparation of film materials with low dielectric constants based on condensation polymers that contain fluorinated and/or alicy- clic units and of polymeric nanofoams. The bibliography includes 147 references. I. Introduction Nowadays, the problem of creating film materials with reduced dielectric constants which can be used as interlayer dielectrics (ILD) in packages of multiintegrated circuits is becoming ever more topical.1, 2 It is known that the velocity of electrical pulses is inversely proportional to e1/2, where e is the dielectric constant (DC) of the medium.3, 4 In addition, the minimum distance between the lines in integrated circuits is limited by `noises' arising because of the `cross effect' dependent on the DC of the insulating material, i.e., currents elicited in conductors near the active signal lines.For this reason, a decrease in e results in the reduction of the machine cycle, and it becomes possible to increase the density of integrated circuits. One of the materials most widely used for ILD is silicon dioxide for which e ranges from 4 to 10 depending on moisture content. Materials with e values lower than that of SiO2 are divided into four basic groups:4 SiO2 modified by fluorine treatment (e=3.0 ± 4.0); organic polymers (e=2.0 ± 3.0); nanofoams of organic polymers (e=1.1 ± 3.0); SiO2 aerogels (e=1.1 ± 4.0).Additionally, the materials for ILD should meet the require- ments for manufacture technologies and operation of circuit elements. These include high thermal stability and mechanical strength in combination with low thermal expansion and residual stress in the thermal cycle. Organic condensation polymers meet these requirements the best, and this review is devoted to the analysis of major achievements in these directions.A L Rusanov, T A Stadnik A N Nesmeyanov Institute of Organoelement Chemistry, Russian Academy of Sciences, ul. Vavilova 28, 117813 Moscow, Russian Federation. Fax (7-095) 135 50 85. Tel. (7-095) 135 63 72. E-mail: alrus@ineos.ac.ru (A L Rusanov) KMuÈ llen Max-Planck-Institut fuÈ r Polymerforschung, Ackermanweg 10, D-55021 Mainz, Germany. Fax (49-6131) 37 91 00. Tel. (49-6131) 37 91 50. E-mail: mullen@mpip-mainz.mpg.de Received 23 November 1998 Uspekhi Khimii 68 (8) 760 ± 772 (1999); translated by V D Gorokhov #1999 Russian Academy of Sciences and Turpion Ltd UDC 561.64 685 685 686 693 694 II. Factors influencing the dielectric constants of polymers The dielectric constant of polymers is mainly influenced by their free volume,5 polarisability 6 and hydrophobicity.7 An increase in the free volume may be regarded as replacement of a portion of a polymer (e'3) by air (e=1) resulting in a decrease in DC of the material.The e value of any material is proportional to the total polarisability (atot), and e increases with the increase in atot. The total polarisability includes components of three types of polar- isation: electronic (ae), atomic (aa) and resulting from dipole orientation (a0):5 ±8 a=ae+aa+a0. The total dielectric constant e is also the sum of increments related to each type of polarisation e=ee+ea+e0. Electronic polarisation is determined by a slight deviation from the equilibrium distribution of electrons relative to the positively charged nuclei with which they are associated.5±8 As this process includes only the motion of electrons, it can occur very fast, and usually the time constant is *10713 s.At optical frequencies, where only optical polarisation can take place, the Maxwell equation operates: e=n2, where n is the refractive index. Atomic polarisation results from changes in the disposition of atomic nuclei under the action of an electric field. This type of polarisation is characterised by a typical time constant of *10713 s. For solid organic compounds, the contribution of a0 to the total polarisation accounts for*10% of ae.5± 8 The polarisation resulting from dipole orientation is the consequence of redistribution of charges, i.e., reorientation of a group of atoms with a constant dipole moment in space under the action of an electric field.Since reorientation involves large-mass particles, the process proceeds more slowly than the electronic or atomic polarisation and is characterised by a time constant of *1079 s even in the gas phase. In this case, it is necessary to overcome high inertia for changing the direction of motion in each cycle of the electrical field oscillation. In the liquid phase and to a larger extent in the solid phase, intermolecular friction forces operate, which also decelerate the process and decrease the a0 values characteristic of the static conditions.686 The polarisation resulting from dipole reorientation often makes the major contribution to the formation of e values of fluids and gases; however, in solids the contribution from ae is often more substantial.Naturally, in solids the mobility of dipoles, which depends on the frequency and temperature of measurements, is increased at temperatures above the glass transition temperature Tg, though appreciable motion of dipoles may also occur below Tg due to b-transitions.8 The dielectric properties of polymers are also dependent on their hydrophobicity,7, 9, 10 since orientation of water dipoles occurs readily and is retained up to high frequencies of the electrical field (1013 Hz for free water). In addition, a water- containing polymer may be regarded as a composite material in which one component (water) has DC equal to 80,7 which makes an appreciable contribution to the additive value of etot of this material.Thus, hydrophobicity of polymers can play an important role in the formation of electrophysical properties of materials. The contributions from the above-listed factors to DC values of polymers can differ substantially on going from one structure to another. Thus the contribution of free volume to the DC of polyimides can vary from 25% to 94% depending on the polymer structure.5 III. Condensation polymers with low dielectric constants Aromatic hetero- and especially carbon-chain polymers (CP) are the most promising materials for the creation of ILD. The greatest attention of researchers was attracted to hydrophobic and non- polarisable fluorinated CP and to polymers with cycloaliphatic fragments.The dependence of e on the frequency of measure- ments, temperature and moisture creates certain difficulties in the establishment of a clear-cut dependence of DC on the structure of polymers. Nonetheless, the available experimental data make it possible to reveal basic regularities and dependences in the structure ±DC relationships for a broad range of CP. As most of the studies analysed in this review are concerned with the film- forming (i.e., high-molecular-weight) systems, the influence of the degree of polymerisation on the properties of the materials was not considered. 1. Fluorine-containing condensation polymers Introduction of fluorine into macromolecules of carbochain polymers results in an increase in their hydrophobicity and free volume with a concomitant decrease in their polarisability.7 Of different approaches to the introduction of fluorine into macro- molecules, those based on the use of monomers with the hexafluoropropane-2,2-diyl groups (HFPG) are the most popu- lar.11 ± 16 The first representatives of HFPG-containing monomers, viz., 1,1,1,3,3,3-hexafluoro-2,2-bis(4-hydroxyphenyl)propane (1), 1,1,1,3,3,3-hexafluoro-2,2-bis(4-carboxyphenyl)propane and its dichloro and 1,1,1,3,3,3-hexafluoro-2,2-bis(3,4-dicarboxyphen- yl)propane dianhydride (2), were synthesised starting from hexa- fluoroacetone according to Scheme 1.These monomers are either used directly for the preparation of aromatic CP or are applied for the synthesis of more complex HFPG-containing monomers.14 In addition to HFPG, trifluoro- methyl 17 ± 20 and other perfluoroalkyl 17, 21 substituents and per- fluoroaromatic fragments 17, 22 ± 24 were incorporated into macromolecules. Among fluorinated aromatic condensation polymers with reduced DC, aromatic polyethers (APE) and polyimides are the most interesting.The most popular method for the synthesis of APE is nucleophilic aromatic polysubstitution 25 ± 27 with bisphenoxides and activated dihalogenoaromatic or dinitroaromatic compounds as the starting reagents. A L Rusanov, T A Stadnik, KMuÈ llen CF3 CF3 HO 1 2PhOH C CF3 F3C O 2PhMe 2C6H4Me2-1,2 CF3 Me CF3 Me Me Me [O] OH CF3 O O O O CF3 OH OH OH CF3 O O O O CF3 Cl Cl O The first fluorine-containing APE O was the polycondensation product of disodium bisphenoxide 1 with 4,40-dibromobiphenyl.28 Fluorine-containing APE of the general formula 3 were obtained by the reaction of dipotassium bisphenoxide 1 with 4,40-difluorobenzophenone, 2,6-difluoroben- zonitrile and bis(4-chlorophenyl) sulfone.22, 29, 30 CF3 nHO OH+nX Ar X CF3 CF3 Ar O CF3 3a ± c (a), X=F, Cl; Ar= CO O (c).SO The dielectric constant of APE 3a ± c characterised by a moisture absorption of *0.9% varies from 2.94 to 3.03 at a relative humidity (r) equal to zero (Table 1). Comparatively high values of e for APE 3a ± c are determined by the presence of such polarisable groups as carbonyl, sulfonyl and nitrile groups in their molecules.The reaction of dipotassium bisphenoxide 1 with bis(4- fluorobenzophenone)-based monomers containing the amide, Scheme 1 OH CF3 Me CF3 Me [O] OH CF3 OO CF3 OHO CF3 O CF3 O 2 CF3 O n CF3 K2CO3, DMAA O n (b) , CNNew condensation polymers having low dielectric constants O CF3 OArO OH + n F nHO OC C F CF3 O CF3 OArO O OC C O CF3 n 4a ± e CN O O O N N (b), (a), Ar= O O N NH O N N O H H N N (d), (e). O O O Table 1. Moisture absorptivity and DC of fluorine-containing APE.22 F F F F O Polymer Moisture absorption (%) e F +nHOArOH n F C r=0 humid medium F F F F F F F 3a 3b 3c 3.25 (r=57.5%) 3.39 (r=67.3%) 3.63 (r=69.0%) 2.94 2.99 3.03 0.91 0.78 1.21 OC F F F CF3 amido-imide, nitrile, 1,3,4-oxadiazole and pyridazine fragments (Scheme 2, see Ref.31) yielded APE 4a ± c belonging to the class of polyetherketones (PEK), which are being intensively studied in the last decades.32 Films based on these polymers are elastic and thermostable. (a), Ar= CF3 (c), At r=0, the dielectric constant of PEK 4a ± e varies from 3.02 to 3.54 (measurements at 10 kHz) (Table 2). The dependence of e on r for PEK 4a is presented in Fig. 1. Table 2. Glass transition (Tg) and destruction temperatures (Td) andDCof fluorine-containing polyetherketones 4.31 Polymer Td /8C Tg /8C humid medium er=0 obtained according to Scheme 3 33 possess rather high thermal stability, while the values of e vary from 2.68 to 2.98 at r=0 and from 2.79 to 3.10 at r=68% (Table 3).The dependences of e on r forPEK 5a ± d are presented in Fig. 2. Comparison of Figs 1 and 2 shows that an increase in r results in an increase in the values of e for fluorinated APE and PEK, this being particularly pronounced for polymers with high moisture absorptivity. 4a 4b 4c 4d 4e 3.51 (r=70%) 3.53 (r=70%) 4.73 (r=54%) 4.54 (r=54%) 4.15 (r=52%) 3.02 3.09 3.11 3.51 3.54 497 498 409 458 366 162 176 146 185 164 Table 3. Glass transition and destruction temperatures and DC of fluorinated polyetherketones 5.33 Polymer Td(air) /8C Tg /8C Polymers obtained using decafluorobenzophenone as the electrophilic monomer have considerably better characteristics.Thus PEK containing the perfluoroaromatic fragments and e 4.50 425 442 436 359 155 175 223 215 5a 5b 5c 5d 4.25 4.00 3.75 3.50 r (%) 40 0 20 To make the dielectric constant of polymers still lower, it is necessary to remove the polar carbonyl groups from their macro- molecules. For this purpose, perfluorinated aromatic hydrocar- bons such as hexafluorobenzene 34 ± 37 and especially decafluorobiphenyl (6) 22 ± 24, 38 ± 45 were used instead of decafluo- robenzophenone for the synthesis of APE. Synthesis of APE based on 6 was carried out according to Scheme 4.22, 24 Figure 1. Dependence of dielectric constant on relative humidity for polyetherketone 4a.687 Scheme 2 K2CO3, DMAA (c), Scheme 3 K2CO3, DMAA F OArO F n 5a ± d Ph (b), Me (d), O O r=68% er=0 2.79 2.95 3.00 3.10 2.68 2.75 2.80 2.98688 e 3.2 3.0 2.8 2.60 20 40 Figure 2. Dependence of dielectric constant of fluorine-containing poly- etherketones 5a (1) 5b (2) 5c (3) 5d (4) on relative humidity.33 F F F F F+nHOArOH n F F F F F 6F F F F F F CF3 (a), Ar= CF3 Me (c). Me A slight excess of 6 was used to prepare polymers with the terminal nonafluorobiphenylyl groups. Some characteristics of fluorinated APE 7a, b are presented in Table 4. Table 4. Electrical and mechanical properties of APE based on decafluo- robiphenyl.40 Property Tg /8C Moisture absorptivity (%) e (n=10 kHz) r=0 r=60% Thermal expansion coefficient a /ppm (8C)71 Td (DTGA) /8C in air in a nitrogen atmosphere Loss of mass at 1000 8C in air (%) Isothermal loss of mass in air (%) 3 h at 400 8C 3 h at 450 8C Tensile elongation Dl (%) Aromatic polyethers of general formula 7 are linear or slightly branched (due to the reaction of more than two fluorine atoms with bisphenoxides) polymers soluble in DMAA, THF, bis-2- 4321 r (%)Scheme 4 K2CO3, DMAA F OArO n F 7a ± c (b), 7b Polymer 7a 260 0.15 189 0.1 2.62 2.66 65 2.50 2.62 76 500 540 37.5 500 510 60 2.7 3.6 36.0 2.5 19.8 85.0 A L Rusanov, T A Stadnik, KMuÈ llen e 2.6 2.5 2.4 r (%) 0 40 20 Figure 3.Dependence of dielectric constant on relative humidity for APE 7a.40 ethoxyethanol and isobutyl methyl ketone. Strong transparent films were prepared by casting from solutions or compression of these APE devoid of carbonyl, sulfonyl, nitrile and other polar groups. Such films have low DC (e42.8) and moisture absorp- tivity (40.1%) and are distinguished by high thermal stability and mechanical strength. Figure 3 gives the dependence of e on r for APE 7a as an example. Fluorinated APE were used to prepare the family of FLARE polymers with low values of e and moisture absorptivity. For example, the values of e for FLARETM 1.0 and FLARETM 1.51 are 2.43 and 2.52 and the coefficients of thermal expansion are 73 and 33 ppm (8C)71, respectively.45 Fluorine-containing polyimides have also attracted the atten- tion of researchers.A drawback of the systems based on polyimides as regards manufacture of materials with low DC is the presence of four carbonyl groups in each repeating unit. However, the possibility to modify their structures (including fluorination) over wide limits in combination with high thermal stability and mechanical strength make polyimides rather attrac- tive materials for this purpose. Polyimides used in electronics have e=2.9 ± 3.4. The decrease in DC is achieved by the introduction of fluorine atoms 5 ± 8, 22, 46 ± 84 into the macromolecules, most often in the form of HFPG5 ± 8, 11 ± 16, 61, 63, 80, 81, 83 and trifluoro- methyl substituents.74 ± 79, 82, 83 Synthesis of fluorinated polyimides is performed mainly with the use of dianhydride 2.This is determined by a relative accessibility of this monomer and by low DC of polymers based on it compared to analogous polymers based on other dianhy- drides (see below). The reaction of 2 with various fluorinated diamines was carried out according to Scheme 5.21, 22, 63 Moisture absorptivity and DC values of the polyimides obtained are listed in Table 5. For comparison, the table also contains the corresponding characteristics of poly(diphenylene oxide pyromellitimide) 9, which is most widely used in micro- electronics as an insulator.85 O O O N N O O n 9 Table 5. Fluorine content, moisture absorptivity and DC of polyimides 8 and 9.Ref. Polymer [F] (%) Moisture e absorp- tion (%) humid medium r=0 8a 8b 2.71 2.72 0.79 0.85 32.0 24.6 8c 2.74 0.71 28.9 22, 30 22, 30 63 22, 30 63 22, 30 3.04 (r=56.8%) 3.02 (r=56.8%) 2.96 (r=50.0%) 2.99 (r=54.5%) 2.78 (r=50.0%) 3.71 (r=58.2%) 9 3.10 2.77 0New condensation polymers having low dielectric constants O CF3 n O CF3 O O ArNO CF3 CF3 Ar= O CF3 CF3 O CF3 F F F O F F F CF3 O CF3 CF3 F F O O F F F O O NHCR1CNH R1=CF(CF3)[OCF(CF3)]mO(CF2)5O[CF(CF3)CF2]nCF(CF3) (m+n=3); F3C OR2 (g), where R2=CH(C6F5)2, CH2(CF2)2CF3; F F F (h), R3 F F F Me F3C (k), (l), Me CF3 Me F F (p), (o), F F It is seen that the parameters of polyimides based on 2 are superior to those of fluorine-free polyimide 9.For polyimides 8, the structure of diamines affects little the moisture absorptivity, DC and changes in DC depending on the relative humidity; however, at r=0 the most attractive seems to be the polymer 8a for which e=2.71. The isomeric polyimide 8d possesses identical properties.83 Fluorinated diamines were used in polycondensation with 2 63 to yield polyimides with high content of fluorine. Dielectric properties of the polyimides 8e ± g are presented in Table 6. For all the polyimides, the largest e values in the temperature range studied were found to be at 300 8C, which is due to the increased mobility of polyimide molecules at this temperature exceeding the Tg of the polymers under consideration.Scheme 5 OO+n H2N Ar NH2 72n H2O O O CF3 N CF3 O n 8a ± c F3C (a), OO (b), F (c), O F (d), O CF3 (e), F (f), F CF3 (i), (j), F F3C F3C F3C (n), (m), CF3 F (r). (q), 689 Table 6. Fluorine content and DC of fluorine-containing polyimides 8e ± g.63 [F] (%) Polyimide e (n=100 kHz, r=50%) 300 8C 250 8C 100 8C 25 8C 8e 8f 8g 2.95 3.00 3.08 2.89 2.82 2.90 2.81 2.91 2.98 2.83 2.93 2.93 24.61 48.06 38.87 An analogous phenomenon was observed 55 in studies of polyimides based on 2 and octafluorobenzidine. Analysis of the data presented in Table 6 made it possible to conclude that the reduction of e is more efficient if fluorine atoms are introduced into the aromatic rings of macromolecules rather than into the aliphatic fragments.63 The reaction of 2 with fluorine-containing substituted m-phenylenediamines NH2 H2N R R=SF5 (a), CF3 (b), OCH2CF3 (c), CH2C(CF3)2C3F7 (d), H (e), yielded polyimides 8h which are characterised by low values of e (Table 7) decreasing in the following order R:H> CH2C(CF3)2C3F7>OCH2CF3>CF3>SF5. Table 7.Dielectric constants of polyimides 8h. Ref. R e n(r=50%) /kHz 66 74 59 68 59 2.51 2.58 2.60 2.70 3.00 106 106 136103 1 SF5 CF3 OCH2CF3 CH2C(CF3)2C3F7 H For polyimides based on 2 andm-phenylenediamines contain- ing fluorinated alkoxy substituents,59, 84 NH2 H2N OCH2(CF2)mX m=3, 6, 7, 10; X=H, F, the values of e are lower than for polyimides based on 2 and nonsubstituted m-phenylenediamine (Fig.4); with an increase in the fluorine content in these polymers, the value of e decreases to 2.6. e 3.5 5 4 3.0 3 1 2.5 2 20 40 [F] (%) Figure 4. Dependence of dielectric constant (at a frequency of 1 kHz) on the fluorine content in polyimides of general formula 8b. R: (1) OCH2(CF2)10H; (2) OCH2(CF2)7F; (3) OCH2(CF2)6F; (4) OCH2(CF2)3F; (5) H.A L Rusanov, T A Stadnik, KMuÈ llen 690 These results may be explained by a decrease in the interchain R O O interactions in polyimides;50 an increase in the length of the fluorinated alkoxy group leads to a steric hindering of the interchain interaction, which, in turn, decreases e. N N O O n 10 ± 12 R=CF3 (10), SF5 (11), CH2C(CF3)3 (12).CF3 Me (b), = ( Si a), CF3 For 10: Me (e) (d), (c), Introduction of fluorinated alkoxy groups is related to two opposite aspects of the influence of fluorine atoms on DC. On the one hand, fluorine has low electronic polarisability,86 due to which DC of a polyimide is reduced. On the other hand, considerable electron affinity determined by the high electronegativity of fluorine atoms 87 favours the appearance of additional perma- nent dipoles on the methylene fragments of the fluorinated alkoxy groups and/or the benzene rings linked with the fluorinated alkoxy groups. These dipoles increase the orientational polar- isation and DC. In polyimides, the contribution of these addi- tional permanent dipoles to DC is smaller compared to those of interchain interactions and electronic polarisation.86 O O CF3 For 11: = ( CF3 a), CF3 Me CF3 (c), (b), Me O O The reduced water and moisture absorptivity of fluorinated polyimides determines the stability of their dielectric character- istics.Thus after the films have been stored for 5 days at 25 8C and r=70%, the increase in e was 0.1 (from 2.6 to 2.7) for the polymer 8h [R=CH2C(CF3)2C3F7] (see Table 7), which indicates that water absorptivity considerably influences the DC of the poly- mers.59 It should be noted that the stability of the DC is one of the most important properties that should be inherent in ILD used in microelectronics.87 O (e), (d), O O O O A detailed investigation of the relationship between the structure of polyimides and their DC has been undertaken.7, 8 Polyimides 8i ± r were obtained based on dianhydride 2 and different diamines with or without fluorine atoms in the benzene rings and side groups.(g), (f), O (h); O For 12: Ph CF3 (b), = ( CF3 a), CF3 O O CF3 The values of e for these polyimides are listed in Table 8. Under all measurement conditions the same trend was observed, viz., a decrease in DC of polyimides with the increase in fluorine content in these polymers. Some deviations from this trend are determined, in particular, by the fact that the methyl-containing polymers with low fluorine content are partially aliphatic, which diminishes the DC.7 It should also be noted that an asymmetrical arrangement of fluorinated fragments in the amine residues leads to an increase in the DC of polyimides with the same number of fluorinated fragments arranged symmetrically.7 An analysis of the results presented in Table 8 shows that the DC of polyimides decreases in the following order: 8r>8q>8o>8p> 8n>8l>8m>8k>8i. (c).CF3 Table 8. Dielectric constants of polyimides 8i ± r. Polyimide r=40% e (1 kHz) r=0 Table 9. Specific viscosity (Zlog), glass transition temperature and DC of polyimides 10. Polyimide Tg /8C e (10 GHz) Zlog /dl g71 10a 10b 10c 10d 10e 2.58 2.75 2.90 2.91 3.02 297 263 294 274 329 0.70 0.64 0.53 0.34 0.89 8i 8j 8k 8l 8m 8n 8o 8p 8q 8r 2.73 72.87 2.90 2.89 3.05 3.21 3.16 3.22 3.19 2.55 2.56 2.59 2.68 2.71 2.72 2.74 2.75 2.81 2.85 Note.Polyimides 10a ± 10d are soluble in DMAA and m-cresol; films can be prepared from solutions of polyimides 10a, 10c ± 10e in m-cresol and DMAA. The effect of the dianhydride structure on the properties of polyimides has been investigated 59, 66, 68, 74 in studies of physical properties (including DC) of polyimides of general formulae 10 ± 12. The results obtained are presented in Table 9. According to these data, the magnitude of e decreases in the following order: 10e>10d>10c>10b>10a. Some characteristics of these polymers are presented in Table 10.It is seen that values of e decrease in the order: 11h=11g>11f>11e>11d>11c>11b>11a. The values of e for SF5-containing polyimides presented in Table 10 are rather low: at a frequency of 10 GHz they vary from 2.51 to 3.00, i.e., they are about 0.2 unit lower than those for the corresponding polymers based on m-phenylenediamine. Analysis of the properties of polyimides of general formula 11 revealed a different dependence.66New condensation polymers having low dielectric constants Table 10. Specific viscosity, glass transition temperature, temperature of 10%-mass loss (DTGA) and DC of SF5-containing polyimides 11. Polyimide Tg /8C T10% /8C e (n=10 GHz) Zlog /dl g71 11a 11b 11c 11d 11e 11f 11g 11h 2.51 2.61 2.68 2.80 2.82 2.83 3.00 3.00 476 480 426 457 470 471 471 461 305 243 300 235 287 263 344 308 0.35 0.44 0.38 0.45 0.48 0.40 0.44 0.40 Similar polyimides with pentafluorosulfanyl (Table 10) and trifluoromethyl (Table 9) substituents, have close e values; some- times the former are characterised by lower e values, which is related to a higher fluorine content in these systems.For the polyimides based on m-phenylenediamines with fluorinated alkoxy groups, the e values decrease in the series of dianhydrides:59 O CF3 > > CF3 Of all of the analysed polyimides, those based on dianhydride 2 and containing the bulky hexafluoropropane-2,2-diyl have the lowest e values compared to polyimides derived from other tetracarboxylic acid dianhydrides.It is the dianhydride 2 that served as the basis for manufacture of polyimide films with e<3.0 (for the Hoechst Sixef film, e=2.6) and low (*0.5%) water absorptivity.61 In later studies,67, 88 ± 90 it was shown that a considerably better combination of mechanical and electrical properties can be reached by introducing fluorine-containing groups into rigid `rod-like' monomers; films of such polymers have low thermal expansions typical of metals and ceramics.91 ± 93 Xanthene-2,3,6,7-tetracarboxylic acid dianhydrides were used for the preparation of rigid-chain fluorinated polyimides (see Refs 94, 95) O O R CF3 O O O O O R=CF3 (a), Ph (b).The reaction of these dianhydrides with a number of the above-mentioned fluorinated diimines yielded polyimides 12, which are characterised by low e values (lower than in polyimides based on 2), low coefficients of thermal expansion and good solubility in organic solvents simultaneously. The properties of this type of polyimides are listed in Table 11.68 Polyimides with even lower thermal expansion coefficients were obtained by the reaction of xanthene-2-3,5,6-tetracarboxylic Table 11. Film thickness (d), tensile strength (s), tensile elongation (Dl), elasticity modulus (Z), thermal expansion coefficient (a), moisture absorp- tivity and DC for films based on fluorine-containing polyimides 12.68 Poly- d Dl Z a s Moisture imide /mm /MPa (%) /GPa /ppm (8C)71 absorption e(1 MHz, (%) (r=85%) r=0) 12a 12b 12c 2.3 2.5 2.7 0.6 1.1 0.5 10.5 116 28 2.0 70 13.6 115 25 1.9 67 6 1.7 86 72 14.6 691 acid dianhydrides with `rigid' fluorinated aromatic diamines, viz., bis(fluoroalkyl)- and bis(fluoroalkoxy)benzidines: R NH2 H2N R R=CF3, OCF3, OCF2CF2H.The rigid-chain polyimides obtained had the following for- mula O O R N N R O O n 13a,b Ph CF3 (b). = ( CF3 a), CF3 O O Some characteristics of such fluorinated polyimides are listed in Table 12.69, 70 Table 12. Fluorine content, tensile strength (s), tensile elongation (Dl), elasiticity modulus (Z), thermal expansion coefficient (a), moisture absorptivity and DC for fluorine-containing polyimides 13.69 R Z a [F] s Dl (%) /MPa (%) /GPa /ppm6 Moisture absorption 6(8C)71 (%) (r=85%) e(n= 1 MHz, r=0) Polyimide 13a 6 6.1 30.7 200 6 CF3 OCF3 2.4 2.7 2.8 3.0 1.2 1.4 0.8 0.7 5.1 10 5.3 10 29.4 411 18 O(CF2)2H 31.7 294 15 Polyimide 13b 5.0 87 CF3 OCF3 2.7 2.6 3.1 1.9 70.8 6.2 3.4 36 4.0 40 22.8 197 21.8 143 O(CF2)2H 24.77 249 19 Polymers based on diamine with the OCF3 substituents are characterised by small values of e, low moisture absorptivities and low thermal expansion coefficients and, at the same time, possess high thermal stability.Such polymers are rather promising as the next-generation materials for microelectronics. Along with fluorinated APE and polyimides, other types of fluorinated aromatic polymers were also used for the production of low-DC materials.Polybenzooxazoles (PBO) 14 are typical representatives of such polymers (Scheme 6).96 ± 98 Despite the fact that introduction of benzooxazole units into macromolecules of polyimides did not result in a decrease in DC Table 13. Dielectric constants of polyimides 14.99 Polyimide e r=70% r=0 14a 14b 14c 14d 3.70 4.29 4.80 4.45 2.88 3.01 3.21 3.21692 CF3 N N O CF3 O O 14a ± d CF3 = (a), (b), CF3 O O n H2N Ph NH2+n Ph H2N O O NH2 of the latter (Table 13),99 highly fluorinated PBO 100, 101 appear to be rather promising polymers for the creation of materials with low DC. In any case, for some fluorinated PBO in the humid state e=2.8 (see Refs 102, 103), and a PBO with e=2.2 ± 2.4 has been reported.104 Yet another promising class of heterocyclic polymers are polyphenylquinoxalines (PPQ).105 ± 107 The information about dielectric properties of PPQ is rather limited,1, 108 but the fact that even a fluorine-free PPQ obtained by Scheme 7 has (depending on the temperature and measurement frequency) e=2.70 ± 3.05 (see Table 14) allows optimistic conclusions about DC of fluorinated PPQ.At present, there are real possibil- ities for the preparation of PPQ containing fluorine in both the phenyl groups 109 and the hexafluoropropane-2,2-diyl `bridges'.110 Table 14. Temperature of measurement, frequency and DC of PPQ of general formula 15.1 T /8C n /kHz e 45 45 100 100 2.86 2.70 3.05 2.82 26101 26103 26101 26103 2. Polymers with alicyclic units In the case of fluorinated polymers, a possibility exists of HF evolution in the course of their processing; therefore, in recent years ever-growing attention is paid to fluorine-free CP containing alicyclic fragments (ACF).The most popular ACF is adamantane and its derivatives.111 In particular, adamantane-containing diamines used as starting compounds in the synthesis of poly- imides have been described.112 ± 116 Polyimides were synthesised by a two-step procedure consisting of low-temperature reaction of adamantane-containing diamines with tetracarboxylic acid di- anhydrides and subsequent solid-phase thermal treatment of the resulting polyamido acids (Scheme 8).Along with the two-step procedure for the synthesis of polyimides, a one-step high-temperature (200 8C) polycyclo- condensation in m-cresol with isoquinoline as the catalyst can also be used to this end. As a rule, this yields higher-molecular- weight polyimides. After incorporation of adamantane-containing fragments, the solubility of some polyimides in organic solvents is enhanced, they are less coloured than the aromatic polyimides and their DC values are diminished. The lowest e values are characteristic of polyimides based on 4,9-bis[4-(4-aminophenoxy)phenyl]diada- O N O n O O (c), C Ph N 74n H2O NO n H2N(AD)NH2+n OO O ADHN HO O O N AD O AD= OO 16 CF3 = (a), CF3 (c), (f), O O O O O A L Rusanov, T A Stadnik, KMuÈ llen Scheme 6 ON O (d).Scheme 7 Ph N N n 15 Scheme 8 O 25 ± 30 8C O O O 300 ± 350 8C NH OH 72n H2O O n ON O n , O , ; O (b), 2 O O (e), (d), 2 O (g), O O (h), (j). (i),New condensation polymers having low dielectric constants Table 15. Specific viscosity (30 8C, N-methylpyrrolidone), glass transition temperature, thermal expansion coefficient, moisture absorptivity andDC of polyimides 16.114 Polyimid Tg /8C a /ppm (8C)71 Moisture Zlog /dl g71 (DSC) e absorption (n=1kHz, (r=85%) r=0) 349 292 394 0.63 0.43 7 16a 16b 16c 16d 16e 16f 16g 2.58 2.65 2.66 2.66 2.67 2.69 2.74 0.122 0.149 0.133 0.149 0.163 0.137 0.264 57.5 67.1 67.8 7 7 72.4 74.9 56.5 41.6 267 319 341 0.80 0.52 7 mantane of the general formula 6.114 Some characteristics of these polyimides are listed in Table 15. Along with the synthesis of polyimides, the diadamantane- containing monomers were also used for the synthesis of poly- benzoazoles.117 IV.Thermostable polymeric foams An alternative to the above approaches to the creation of polymeric materials with low DC is the use of thermostable polymeric foams.1, 118 ± 132 Polymeric foams were prepared from microphase-separated block- or graft-copolymers composed of thermostable and thermolabile blocks, the latter forming the dispersed phase.1 The thermally degradable block should be a functional oligomer of a strictly determined structure; further- more, it should undergo quantitative disintegration into non- reactive species that diffuse easily through a glassy polymeric matrix.The temperature of destruction of unstable blocks must be sufficiently high to allow preparation of standard films with the removal of a solvent; at the same time, it must be considerably lower than the glass transition temperature of the polyimide block in order to avoid foam degradation.121 Hence, the difference between the temperature of unstable block destruction and the glass transition temperature of the polymeric matrix determines the `processability window' of the material.Upon heating, the thermally unstable blocks undergo degradation to produce pores, the size and shape of which are determined by the morphology of the initial copolymers. This type of foams having pores of about 1 nm in size are called nanofoams.1Adecrease inDCis achieved by replacing part of a polymer with e=3.2 by air with e=1 (see Ref. 1). O O O R X N N N O O O x 17a ± b O O O O N N N N R O O O O x18a,b R=fluorene-9,9-diyl; X=PPO; O = (a), (b). 693 The choice of different polyimides,118 ± 130 PPQ 1 or PBO,131 as thermostable polymeric matrices is determined by their high thermal stability together with solubility (at least, at the prepol- ymer stage) in organic solvents. The following polymers are most often used as thermolabile blocks: poly(propylene oxide) (PPO),1, 118 ± 122, 124, 125, 128, 129, 131 poly(methyl methacrylate) (PMMA),1, 124 polystyrene,123, 125 poly-a-methylstyrene 123, 125, 127 and aliphatic polyethers.126 Examples of such systems are amorphous polyimides based on a card diamine, 9,9-bis(4-aminophenyl)fluorene, with the terminal (17) or lateral (18) PPO blocks (Scheme 9).118, 121 In the synthesis of polyimides 17a,b the second amine component was PPO p-aminobenzoate; in the case of 18a,b part of the card diamine was replaced by PPO 3,5-diaminobenzoate.Films of soluble polymers 17a and 18a were obtained from solution, whereas films of insoluble polymers 17b and 18b were prepared in the stage of soluble polyamido acids with subsequent thermal cyclisation.Conditions of this stage (300 8C, 5 ± 10 h) allowed formation of foams of both polyamide 17 and polyamide 18. The density of the polymers points clearly to the formation of intumescent structures: the density of matrix polyimides is 1.28 g cm73, while those of nanofoams range from 1.09 to 1.27 g cm73 (see Ref. 121). Thus, the volume fraction of pores makes up from 15% to 1%. Nanofoams based on copolymers of PPQ (matrix) and PPO or PMMA (terminal blocks) were prepared using for their synthesis the monomer ± oligomer approach according to the following scheme: NH2 H2N O O + + H2N NH2 Ph C6H4X C(O)C(O)Ph + PhC(O)C(O) X(Z)X 19 X=PPO (a), PMMA (b); Z=PPQ. In order to induce destruction of terminal blocks, films of copolymers 19a, b were heated in air for 9 h at 275 8C and for 5 h at 340 8C, respectively.The density of intumescent polymers reached 1.16 ± 1.19 g cm73, which is appreciably lower than the density of a PPQ homopolymer (1.32 g cm73). Accordingly, 10%± 12% of the film volume were voids. Some characteristics of intumescent polymers are listed in Table 16. It is seen that e decreases from 2.7 for PPQ homopolymer to 2.31 for intumescent copolymers 19a. Scheme 9 O X N O y X694 Table 16. Density, temperature of measurement, frequency and DC of a PPQ homopolymer and its intumescent copolymers.1 T /8C n /kHz r /g cm73 PPQ ±PPO copolymer 1.16 2026103 2026103 45 45 100 100 PPQ ±PMMA copolymer 1.19 2026103 2026103 45 45 100 100 PPQ homopolymer 1.32 2026103 2026103 45 45 100 100 The results obtained confirm unequivocally the efficiency of this approach to the preparation of materials with low DC.V. Conclusion The data analysed in this review point to an appreciable progress in the preparation of polymers and polymeric materials with low DC. At present, polyimides meet best the requirements for the dielectric materials employed in microelectronics;132 however, these requirements are becoming more rigorous, which stimulates further search for new materials. Computer-assisted analysis of different structures of polymers has shown 133 that considerable progress may be expected if heterochain and heterocyclic polymers are replaced by phenyl- substituted polyphenylenes devoid of polar groups such as C=O, C=N, etc.present in polyheteroarylenes. Polymers of this type were obtained from phenyl-substituted biscyclopentadienones and diethynylarylenes by the Diels ± Alder reaction.134 ± 137 In this case, polyphenylenes with aliphatic 135, 136 and hexafluoropropane-1,2-diyl 137 groups were obtained along with the simplest systems containing only aromatic rings.134 Apparently, polymeric materials with e=2.50 ± 2.60 will be prepared based on various modifications of these systems. Yet another promising direction of studies aimed at the creation of low-DC materials appears to be synthesis of `cross- linked' polycyclotrimers of fluorinated cyano esters 20.138 ± 142 These polymers, obtained according to the scheme,140 O O N A O NCO A OCN N N O 20 A=CH2(CF2)nCH2; n= 3, 4, 6, 10, are reported 140 to have the record DC values for homogeneous systems (e'2.27).Taking into account the efficiency of the approach to the preparation of nanofoams, it may be expected that materials with uniquely low DC will be obtained based on 20. The same object is pursued by studies in the field of maleimides, norbornenes, benzocyclobutenes and propargylic com- pounds.143 ± 147 e2.38 2.31 2.36 2.31 2.55 2.51 2.54 2.50 2.86 2.70 3.05 2.82 O N N N O A L Rusanov, T A Stadnik, KMuÈ llen References 2. C Pan, T Ali, Y Ling C Chiang Am. Chem. Soc. Polym. Prepr. 37 (1) 1. 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ISSN:0036-021X    

出版商:RSC    

年代:1999

数据来源: RSC

摘要:

Russian Chemical Reviews 68 (8) 697 ± 707 (1999) Novel insecticides and acaricides A F Grapov Contents I. Introduction II. Heterocyclic derivatives III. Natural compounds IV. Pyrethroids and other compounds Abstract. This review outlines the major achievements in design of novel chemical insecticides and acaricides, especially those with non-standard mechanisms of action, viz., neonicotinoids and oxidative phosphorylation decouplers. The bibliography includes 119 references. I. Introduction The assortment of modern commercially available insecticides and acaricides is rather wide and permits solution of virtually any problem associated with protection of plants against insects and mites. Nevertheless, studies aimed at improving the preparation forms and the methods of their application do not stop.The need in the search for new highly effective groups of compounds with unusual mechanisms of action and the development of novel insectoacaricides is dictated by both economical considerations and the more rigorous requirements of the health and ecological characteristics of chemicals from the aspect of pesticide industry controlling institutions. Novel, highly effective and selective pesticides with usage rates of about 10 ± 100 g ha71 not only cut the finance, energy and labour expenditures per unit area treated but also decrease the impact of chemicals on the environment and enhance the safety of their application. Unfortunately, the high cost of the development and marketing of new pesticides ($US 100 ± 200 million per a product) has led to a decrease in the number of companies specialising in this problem.Since the development of every novel pesticide represents a complex and multifactor problem, its successful solution can only be attained based on joint achievements in fundamental and applied sciences of different profiles. In the design of novel pesticides, one should pursue not only high efficacy of a novel product against pests but also its compatibility with other insectoacaricides in multicomponent systems used in integrated plant protection against insects and mites, especially against pesticide resistant populations. Thus, nowadays there are pop- ulations of more than 500 species of arthropod, which are resistant to organophosphorus, carbamate and halogen-containing insec- toacaricides, including pyrethroids.In order to overcome this resistance or, in the other words, to develop systems of pesticide A F Grapov Institute of Plant Protection Chemicals, Ugreshskaya ul. 31, 109088 Moscow, Russian Federation. Tel. (7-095) 279 55 40 Received 18 January 1999 Uspekhi Khimii 68 (8) 773 ± 784 (1999); translated by S V Chapyshev #1999 Russian Academy of Sciences and Turpion Ltd UDC 632.951.2%547 697 697 704 705 alternation preventing the appearance of resistant populations in insects and mites, one should have at one's disposal pesticides with different mechanisms of action. The nerve pulse, hormonal status of the insect and mite moulting process and metamorphosis, and oxidative phosphor- ylation may be distinguished as three vitally important functions disbalancing of which is currently used to suppress the mite and insect populations.Among these three, the nervous system is the most vulnerable and it is no surprise that the majority of insectoacaricides (more than 90%) block the conductivity of nerve fibres. Thus pyrethroids act on the neuronal sodium channels, carbamates and organophosphorus compounds (OPC) suppress the activity of acetylcholinesterase, whereas nereistoxin analogues block the acetylcholine receptors. A group of insecto- acaricides that disturb the hormonal regulation of the moulting process and metamorphosis or block chitin biosynthesis is also used in the pest control programmes.So far, only the first steps have been made in the development of insecticides which decouple mitochondrial oxidative phosphorylation. The present review is mostly devoted to novel insectoacar- icides with unusual mechanisms of biological action. II. Heterocyclic derivatives The most impressive results and those interesting from the practical point of view, giving birth to new promising directions in the research and development of insectoacaricides, have been obtained for heterocyclic compounds belonging to derivatives of the pyrrole, pyridine, pyrazole and imidazole series. 1. Pyrrole derivatives Pyrrole derivatives such as synthetic analogues of the antibiotic dioxapyrrolomycin (1) are of considerable interest as insecticides. This antibiotic has been isolated from Streptomyces and exhibited moderate toxicity against insects and mites.The mechanism of biological action of compound (1) consists in inhibition of electron transport during the mitochondrial oxidative phosphor- ylation. Cl Cl NO2 H Cl Cl HN O O 1 It was shown 1±4 that certain derivatives of compound 1, first of all, such as 2- and 3-arylpyrroles, bearing electron-withdrawing substituents in positions 3,4 or 2,4 of the benzene ring, possess698 enhanced insecticidal activity. The fairly high efficacy against various insect species has been found for 2-(4-chlorophenyl)-3- cyano-4-halogeno-5-trifluoromethylpyrroles 2a ± c, 3-aryl- 4-halogeno-5-trifluoromethyl-2-trifluoromethylsulfenyl(sulfinyl, sulfonyl)pyrroles, 2-aryl-4-halogeno-5-trifluoromethyl-3-triflu- oromethylsulfonylpyrroles and 2-(4-chlorophenyl)-3,4,5-tris(tri- fluoromethyl)pyrrole.5, 6 Compound 2a (AC-303630) is the most potent insecticide in this series. At doses of about 125 ± 250 g ha71 this compound is effective against 35 insect species from16 families and 5 orders;2, 3, 7 its LD50 for rats is 223 ± 459 mg kg71.Y CN F3C C6H4Cl-4 2a ± c NR R=CH2OEt, Y=Br (a), F (b); R=H, Y=Br (c). The insectoacaricidal activity of compound 2b, 5-aryl-2-(2- bromo-1,1,2-trifluoroethylthio)pyrroles 3 and the products of intramolecular cyclisation of the latter, viz., pyrrolo[2,1-b]thia- zoles 4, is comparable with that of compound 2a.8Y X CHFBrCF2S N S NH3 X F F 4 X, Y are electron-withdrawing groups.The most convenient method for the preparation of pyrrole 2a consists in the treatment ofN-(4-chlorophenyl)trifluoroacetamide with phosphorus pentachloride and subsequent cyclocondensa- tion of the resulting imidoyl chloride with 2-chloroacrylonitrile in DMF. 5-(4-Chlorophenyl)-5-cyano-2-trifluoromethylpyrrole 5 thus obtained is brominated in the presence of sodium meth- oxide, and pyrrole 2c, in turn, is alkylated with diethoxyme- thane.9, 10 Cl H2C C(Cl)CN PCl5 4-ClC6H4NHCOCF3 4-ClC6H4N CCF3 DMF CN CN Br CH2(OEt)2 Br2 2a MeONa C6H4Cl-4 F3C F3C C6H4Cl-4 2c NH 5 NH Studies on the mechanism of action of compound 2a showed that in the insect organism this compound is activated through the oxidative dealkylation producing derivative 2c, which acts as an inhibitor of oxidative phosphorylation blocking electron trans- port during ATP synthesis in the mitochondrial chain.11, 12 As has already been mentioned, this mechanism of action is rather untypical for pesticides.Such a mechanism explains fairly well the absence of cross-resistance to compound 2a among those insect populations which are resistant to the action of OPC, carbamates and pyrethroids. 2. Pyridine derivatives (neonicotinoids) The group of compounds under consideration can be referred to as pyridine derivatives rather arbitrarily. The history of the development of these insecticides is quite interesting. In 1978, at the 4th International Congress on Pesticide Chemistry, Soloway et al.13 presented a report on the study of insecticidal activity of nitromethylidenepyridines, monocyclic and bicyclic nitromethyli- denepiperidines and other five- and six-membered heterocycles and acyclic nitromethylidene derivatives.It was shown that 3-nitromethylidenetetrahydrothiazine (6) is several times more active against larvae of Lepidoptera than parathion. S CHNO2 NH 6 This finding has stimulated studies on insecticidal properties of numerous acyclic, carbo- and heterocyclic compounds contain- ing the nitromethylidene, cyanomethylidene, nitroimino and cyanoimino fragments of the general formula 7. R1X YR2 Z In the beginning, these investigations were unsuccessful and only when 6-chloro-3-pyridylmethyl substituents were introduced did the results obtained surpass all expectations! It is for this reason that this group of compounds is referred to as pyridine derivatives. Selected data on the activity of N-nitroimino- and nitroiminomethylideneimidazolidines and -thiazolidines are listed in Table 1.Overall, several thousand compounds of the general formula 7 have been synthesised and assayed. Table 1. Insecticidal activity of some neonicotinoids of the general formula 7 (X=N) against rice green leaf hopper.14, 15 R1 PhCH2 4-ClC6H4CH2 Me CH2 N Me N CH2 CH2 Me N CH2 N F CH2 N Cl CH2 S Cl N a Relative activity was determined as a ratio of the LC90 value for imidacloprid to that for the specified compound.A new systemic insecticide 1-(6-chloro-3-pyridylmethyl)-2- nitroiminoimidazolidine (7a, imidacloprid), is widely used for seed dressing and treatment of soil and green plants. Cl N A F Grapov R1=H, Alk, Ar, Bn, HetAr, HetArCH2; R2=Alk; X, Y=N, S, CH; Z=CHNO2, CHCN, YNO2, NCN. 7 Relative activity a Z Y R2LC90 /mg litre71 0.0016 0.008 200 40 HH NN CHNO2 CHNO2 0.0016 200 H N CHNO2 0.04 8 H N CHNO2 0.2 1.6 H N CHNO2 1 0.32 H N CHNO2 HHMe 0.32 0.32 1.6 0.32 1.6 CHNO2 NNO2 NNO2 CHNO2 NNO2 110.2 10.2 NNNSS 0.32 200 CHNO2 CHNO2 10.016 HH NN NH N 7a NNO2Novel insecticides and acaricides Imidacloprid (7a) is employed against aphids, whiteflies, sawflies, flies, moths, leaf hoppers and noctuids at the usage rates of 30 ¡À 100 g ha71 (see Refs 14 ¡À 18).This is one of the most effective insecticides, which is not inferior to pyrethroids and surpasses OPC and carbamates in activity. The scale of its application is rapidly growing and presumably in the beginning of the XXIst century this will achieve the scale of application of pyrethroids. This is a very promising agent for preventing the appearance of resistant aphid populations. If pesticides are alternated in the series: compound 7a?bifenthrin?chlorpyri- fos?amitraze, a resistance of aphids to these preparations is not developed. Imidacloprid (7a), being an agonist of nicotinic acetylcholine postsynaptic receptors, suppresses the activity of acetylcholines- terase and induces hyperpolarisation of a nerve fiber membrane in insects.The complex mechanism of its action is reduced to the prolonged opening of the sodium channels.19 ¡À 21 The mode of action of compound 7a and of its analogues resembles that of nicotine, and therefore this group of compounds has been named neonicotinoids. Imidacloprid (7a) is bound fairly well to the cerebral membrane of cockroaches, flies, bees and other insects, but very poorly to the cerebral membrane of vertebrates. This probably is the basic reason for its selective toxicity. In cock- roaches, the main site of the action of compound 7a is the synapse of the sixth ganglion.22, 23 According to the X-ray data of the molecule of compound 7a, the C=NNO2 fragment and the imidazolidine ring are coplanar, the C7N bonds are shortened and the C=N bond is prolonged. Based on these data, two possible alternative schemes for the binding of compounds 7 to receptors have been suggested (a or b, Fig.1). a b O N O H X Cl HN N N N N N R H H O2N nAChR nAChR 5.9A �º 5.9A �º Figure 1. Schemes of interaction of imidacloprid (7a) with nicotinic acetylcholine receptors (nAChR). The assumption of the existence of two distinct mechanisms for the binding permits one to rationalise both the high efficacy of compound 7a and the lack of the cross-resistance to this agent.24 Imidacloprid (7a) is obtained by the reaction of nitroguani- dine with ethylenediamine followed by alkylation of 2-nitroimi- noimidazolidine (8) with 2-chloro-5-chloromethylpyridine.25 (H2N)2C NNO2+H2NCH2CH2NH2 ClCH2 Cl NH HN N 7a NNO2 8 Compound 7a is insufficiently effective against Lepidoptera. Its thiazolidine analogue 9, obtained according to the scheme shown below,23 can be successfully employed against insects which are relatively resistant to the action of imidacloprid (7a).699 SMe S O2NCH2CO2Et Me2SO4 N S N +S Cl Cl N N MeSO¡¦4 EtOOC NO2 NO2KOH, D S N S N Cl N N Cl 9 For example, the LC90 values for compounds 7a and 9 against rice green leaf hopper, cabbage looper Trichoplusia ni, cabbage moths and leaf roller Cnaphalocrosis medinalis are equal to 0.32 and 0.32, 40 and 1.6, 200 and 1.6, 200 and 8 mg litre71, respectively.23 After discovery of the insecticidal properties of imidacloprid (7a) and its analogues, the antibiotic epibatidine (10), containing the 6-chloro-3-pyridyl fragment and possessing anti-cholinester- ase and high analgesic activities, was isolated from the skin of the poisonous frog Epipedobatis tricolor.This antibiotic is highly toxic against aphids and spider mite Tetranychus telarius (LD50 0.5 and 6 mg litre71, respectively).26, 27 NH Cl N 10 1-(N-Alkyl-N-hetarylmethyl)amino-1-methylamino-2-nitro- ethylenes 11 also possess high insecticidal activity. At a dose of 0.8 mg litre71 these compounds cause 100% death for cicada Nilaparvata lugens. Different modifications of the molecule 11 (replacement of the chlorine atom in the pyridine ring by the methyl or methoxy group, elimination of the methylene group or its replacement by the double or triple bond) do not lead to the enhancement of the biological activity.25 NO2 N HetAr NHMe 11 Alk S ; X=Cl, F, Br., HetAr = N N X Cl The most effective insecticide in this group of compounds is 1-[N-(6-chloro-3-pyridylmethyl)-N-ethylamino]-1-methylamino- 2-nitroethylene (11a, nitenpyram), which is currently undergoing field testing as an aphicide. NO2 NCNMe NHMe NMe 12 NEt 11a N Cl Cl N The replacement of the nitromethylidene group by the cyanoimino group resulted in 1-(6-chloro-3-pyridylmethyl)-1,3- dimethyl-2-cyanoguanidine (12, acetamiprid).This compound, having the contact and systemic mode of action, is highly toxic against aphids, cabbage fly, army worms Spodoptera litura and Mamestra brassicae, whitefly and tobacco thrips in concentrations of 0.056 ¡À 13.4 mg litre71.28 In protecting the leaves against tobacco whitefly and cotton aphids, compound 12 considerably surpasses imidacloprid (7a).700 3. Derivatives of heterocycles with several heteroatoms in the ring In some cases, the 2-chloro-5-thiazolyl moiety can successfully mimic the 6-chloro-3-pyridyl fragment in compounds of the nitromethylidene and nitroguanidine series, and the correspond- ing compounds manifest the neonicotinoid type of insecticidal activity. (E)-1-(2-Chlorothiazol-5-ylmethyl)-3-methyl-2-nitro- guanidine (13, TI-435) in small doses kills sucking and chewing insects.28 NNO2 S Cl NHMe N N 13 H Pyrazole and pyrazoline derivatives constitute one of the basic groups of compounds which were employed in the search for novel insectoacaricides over the last 15 years. The activities of such compounds as substituted anilides of 1-alkyl- and 1-arylpyrazole- 5-carboxylic acids, 1-arylpyrazole-3-carboxylic acids, 1,5-diphe- nylpyrazoline-3-carboxylic acids, 1-arylpyrazoline-3-carboxylic acids, 3,4-disubstituted 1-alkyl- and 1-aryl-5-aminopyrazoles, substituted oximes of pyrazole-4-carbaldehydes have been studied in detail.29 One of the most original preparations of this group of compounds is O-4-tert-butoxycarbonylbenzyl-1,3-dimethyl-5- phenoxypyrazole-4-carbaldoxime (14, fenpyroximate), which is a 10 ± 100-fold more effective acaricide against mites Tetranychidae, Tarsonemidae and Eryophydae than dicofol and cyhexatin.This compound not only gives rapid knockdown in mobile stages but also suppresses the moulting process in larval stages of mites.30, 31 Me NO N OPh CO2But NMe 14 Fenpyroximate 14 acts as an inhibitor of the NADH-coen- zyme Q-reductase, which is responsible for the electron transport in the process of mitochondrial oxidative phosphorylation.32 The starting compound in the synthesis of fenpyroximate 14 is 1,3-dimethylpyrazolin-5-one (15), which is simultaneously formy- lated and chlorinated at the 5-position by the reaction with a mixture of POCl3 and DMF.Successive treatment of the aldehyde 16 with sodium phenoxide, hydroxylamine and 4-t-butoxycar- bonyl)benzyl chloride gives compound 14 in high yield.33 CHO Me Me CHO Me POCl3 H2NOH PhONa N N N DMF OPh O Cl NMe NMe 15 NMe 16 Me NOH ButO2CC6H4CH2Cl-p N 14 OPh NMe A novel acaricide, viz., N-(4-tert-butylbenzyl)-4-chloro-3- ethyl-1-methylpyrazole-5-carboxamide (17, tebufenpyrad), has been synthesised based on pyrazole-5-carboxylic acid derivatives. CONH Cl But NMe Et N 17 At concentrations of 50 ± 200 mg litre71 this agent is acute against mites Tetranyhus sp., Panonychus sp., Orygonychus sp. and Eotetranychus sp. in all stages of their development, including even those populations, which are resistant to the action of dicofol, fenbutatin and hexythiazox.34 ± 38 Compound 17 acts as A F Grapov a systemic and translaminar acaricide.Its mechanism of action resembles that of compound 14 and involves the decoupling of the oxidative phosphorylation process.10 A detailed study of the chemical structure ± biological activity relationships for ana- logues of 17, using the QSAR programme, has led to the design of a novel insecticide, viz., N-[4-(3-methylphenoxy)benzyl]-4- chloro-3-ethyl-1-methylpyrazole-5-carboxamide (18, OMI-88), having a broad range of action.39, 40 CONH Cl Me O NMe Et N 18 This agent is highly effective against cabbage moth, aphids, whitefly, leaf hoppers and thrips in concentrations of 75 ± 150 mg litre71 without inducing cross-resistance to pyreth- roids, OPC and phenylbenzoylureas in insects.41 Analogues of 17 and 18 containing 3-pyridylmethyl fragments instead of the benzyl one are less effective against spider mites.42 Bicyclic pyrazole derivative 19 is not inferior in activity to compound 18.According to the data of X-ray analysis, both compounds have similar crystal structures.43 Me N CONH NMe 19 But Compound 18 and its analogues were synthesised by cyclisa- tion of alkyl a,g-dioxocarboxylates with methylhydrazine fol- lowed by the chlorination and aminolysis.44 Et Et a, b MeNHNH2 17 N O CO2Et CO2Et O NMe (a) Cl2; (b) H2NCH2C6H4But-p. Further variation of the structure by introduction of polar and non-polar substituents in the pyrazole ring has led to the design of a fine soil and seed treating insecticide, viz., 5-amino-3-cyano-1- (2,6-dichloro-4-trifluoromethylphenyl)-4-trifluoromethylsulfinyl- pyrazole (20, fipronil).This agent is employed against soil insects at doses less than 100 g ha71. Compound 20 is effective not only against susceptible insect populations but also against those resistant to dieldrine, cypermethrin and carbaryl.45 ± 48 NH2 Cl CF3SO CF3 NC N N20 Cl Insecticidal aminopyrazoles of the fipronil group (derivatives of compound 20) are antagonists of the GABA-receptors. They block the GABA-regulated chloride channels in a membrane of the nerve fibres of insects. For the aminopyrazole 20, the degree of blocking of the chloride channels in a membrane of the nerve cells of flies is much higher than that in a membrane of the nerve cells of rats.48 Astudy of the chemical structure ± biological activity relation- ships for compounds of the type 20 has shown that introduction of a 2,6-dichloro-4-trifluoromethylphenyl substituent at the nitrogen atom of heterocycles enhances the insecticidal properties.Accord- ing to the data of quantum-mechanical calculations, compound 20 and its pyridone (21) and pyrimidone (22) analogues have very similar electrostatic surfaces.47, 49 All of them are potent insecti- cides.Novel insecticides and acaricides Cl Cl O O CF3 CF3 F5C2 N N F3C N Cl Cl 22 21 The insecticidal activities of 1-(2,6-dichloro-4-trifluorome- thylphenyl)-1,2,3- (23) and -1,2,4-triazoles 24 as well as of 5-tert- butyl-4-(2,6-dichloro-4-trifluoromethylphenyl)-1,3,4-oxadiazolin- 2-one (25) are substantially lower than that of compound 20.50 ± 52 Most likely, aminopyrazole 20 and compounds 23 ± 25 have different electrostatic surfaces.O NH2 CF3CHMe CF3SO2 N RN O NR NR N N N N But 24 25 23 Cl CF3 . R= Cl In comparison with the pyrazole derivatives, their pyrazoline analogues are less potent insectoacaricides. However, a novel insecticide, 4-methoxycarbonyl-3-(3-chlorophenyl)-4-methyl-1- [N-(4-trifluromethylphenyl)carbamoyl]-4,5-dihydro-5H-pyrazole (26, RH-341), has also been found in this group of compounds. Compound 26 acts as an inhibitor of the conductivity of sodium channels, which are blocked, as a rule, by veratridin, batracho- toxin and pumylotoxin B.It is important to note that compound 26 is bound to the sodium channels at the sites different from those for alkylamides, pyrethroids and DDT analogues.53, 54 N NC(O)NH CF3 Cl Me 26 CO2Me Compound 27 of the similar structure is effective against various species of noctuids. Methods of optimisation of the biological properties using correlation analysis have been applied in the design of this agent, in which the primary attention has been focused on the increase in lipophilic characteristics of the molecule.55 MeOSO2O7 + MeN NC(O)NH OCF3 F 27 Me2NCH2 The trihalogenoimidazole derivatives represent another exam- ple of insecticides of non-standard mechanisms of biological action. They can be employed against insect populations resistant to other insecticides. The most active agent in this series of compounds is 2-bromo-1-methoxymethyl-4,5-dichloroimidazole (28a), which is highly effective against cockroaches.56 CH2OR Cl N X Cl N 28a,b R=Me, X=Br (a); R=(CH2)4Cl, X=Cl (b).The mode of action of trihaloimidazoles has been studied in detail using 1-(4-chlorobutoxymethyl)-2,4,5-trichloroimidazole (28b, S-377) as a model compound. Like pyrethroids, this agent inhibits the inactivation system of the sodium channels in a membrane of nerve cells thus inducing huge excitation poten- 701 tials. However, the binding sites of trihaloimidazoles and pyreth- roids to the sodium channels have been found to be different.57 Insecticides of the class of 1,5-disubstituted imidazoles sup- press the activity of insect juvenile hormones disturbing the growth, development and diapause of insects.The mechanisms of their activities are highly diverse and depend substantially on the substituents in the imidazole ring. Thus 1-cyclohexyl-5-(2,6-dimethylhepta-1,5-dienyl)imidazole (29, KK-85) and particularly 1-sec-butyl-5-(3-phenoxy- phenyl)imidazole (30, KK-98) at concentrations of 1077 ± 1078 mol litre71 not only selectively inhibit the farnesoate epoxidases, but also suppress the activity of O-methyl farnesoate transferase.58, 59 EtMeCHN C6H11-cyclo N O N 30 29 N Compound 31, 1-benzyl-5-(2,6-dimethylhepta-1,5-dienyl)- imidazole (KK-42), which is structurally close to imidazole 29, suppresses in vitro at low concentrations the biosynthesis of ecdisteroids in protoracal glands of silkworm and reduces the ecdisteroidal titre in hemolymph of silkworm larvae and pupae.This compound induces premature metamorphosis of silkworm larvae, which is eliminated by methoprene and 20-hydroxyec- disone.60 CH2Ph N 31 N Terpenoids having the 2,7-dimethyloctane skeleton and a benzimidazolyl substituent, (32, 33) were obtained by catalytic alkylation of benzimidazole. They possess growth regulating properties toward mealworms Tenebrio molitor.61 N N N N 33 32 A rather unexpected mechanism of action has been found for such acaricides as N-substituted iminoimidazolidines and thiazo- lidines 34a,b.Et NH N X Et 34a,b X=NH (a), S (b). These compounds suppress the octopamine-sensitive adeny- latecyclase.62, 63 The products of 1,3-dipolar cycloaddition of diazomethane to Schiff bases, such as 1,5-diaryl-4,5-dihydro-1H-1,2,3-triazoles 35, exhibit the aphicidal properties. The detailed study of the mode of their action has shown that compounds 35 are in fact proinsecti- cides. Upon UV irradiation, they are converted to 1,2-diary- laziridines 36, which exhibit the aphicidal properties. Ar O O N hn N Ar0N CHAr +CH2N2 7N2 H2O N Ar NAr Ar0 36 35702 Model experiments have shown 64 that specially synthesised aziridines of the general formula 36 indeed manifest the same or higher activities against aphids.1-Fluoro-1,1-bis(4-trifluoromethoxyphenyl)-2-(N-tetrazolyl)- propane 37 is comparable with pyrethroids in the level and the range of insecticidal activity. The mechanism of its action consists in the blockage of the axonal calcium-dependent potassium channels.65 F3CO N NN CFCHN N N Ar Me N N HO 38 F3CO 37 3-Aryl-2-(N-tetrazolyl)propanols 38 possess a good larvicidal activity against mosquito larvae and prevent the development of army worms Spodoptera litura.66 Some groups of derivatives of six-membered heterocycles with two heteroatoms in the ring also exhibit high insectoacaricidal activity. Each certain group has its own, specific mode of action. Thus 5-chloropyridazin-6-one derivatives are agonists of juvenile hor- mone and stimulate the biosynthesis of this hormone by activating the productivity of prothoracal glands corpora allata. This group of compounds not only suppresses the metamorphosis of insects, but also disturbs many other vitally important processes such as pigment biosynthesis, embryogenesis and diapause.5-Chloro-4-(6-chloro-3-pyridylmethoxy)-1-(3,4-dichloro- phenyl)pyridazin-6(2H)-one (39, NC-170) is employed as an experimental insecticide against leaf hoppers.67 ± 69 Another compound of this group, viz., 1-tert-butyl-4-(4-n- butylbenzylthio)-5-chloropyridazin-6(2H)-one (40, pyridaben, NC-129), is effective against whitefly, aphids and thrips in all stages of their development. This is a tenfold more effective acaricide against mites of the orders Tetranychus and Panonychus than cyhexatin.70, 71O Cl Cl NN O Cl N Cl 39 O Cl ButNN S C6H4Bun-4 40 Being genetically associated with the group of juvenile hormone mimetics, 1-benzyl-4-(2-ethoxycarbonylamino)ethoxy- pyridazin-6(2H)-one (41) is of certain interest.This compound is more effective against rice green leaf hopper than fenoxycarb. It has systemic type of activity and can be applied in granulated form against soil pests at a usage rate of 200 g ha71.72 O Ph NN NHCO2Et O 41 In the series of substituted pyrimidines, 4,6-diamino-5-cyano- 2-cyclopropylaminopyrimidine (42, CGA-193893) is the most interesting experimental insecticide with the hormonal mode of A F Grapov action.This compound is tenfold more effective against aphids, pupae and imago of flies, mosquitoes and lice than cyromazine.73 NH2 CN N NH N NH2 42 N-Substituted 6-alkyl-4-amino-5-chloro- and 6-alkyl-4- amino-5-cyanopyrimidines, e.g., compound 43, are active against both phytophagous mites and noctuids.74 PhMeCHNHCl N Et N 43 Among quinazoline derivatives, 4-[2-(4-tert-butylphenyl)- ethoxy]quinazoline (44, fenazaquin) can be distinguished as an interesting acaricide with ovicidal and larvicidal types of activity and with good ecological characteristics. Its usage rates are only 1 ± 15 g ha71, and 85% of the preparation is decomposed after 7 days. As regards the mechanism of its action, fenazaquin is assigned to a new group of insecticides, viz., the mitochondrial oxidative phosphorylation decouplers.75 ± 78 N N O C6H4But-4 44 Analogues of compound 44 containing the pyridopyrimidine, thienopyrimidine, pteridine, pyrazolopyrimidine, purine, isoxa- zolopyrimidine and isothiazolopyrimidine fragments instead of the quinazoline moiety also possess acaricidal activity.78 3-(3-Pyridylmethylideneamino)-3,4-dihydroquinazolin-2-one (45) was obtained from 1-aminoquinazolin-2-one and nicotinal- dehyde.79At usage rates of 75 ± 150 g ha71 this compound is effective against aphids resistant to pyrethroids, OPC and carba- mates but does not affect useful insects.OHC NNH2 + O N NH N N N O NH 45 An analogous derivative of an asymmetrical triazine, viz., 2,5-dihydro-6-methyl-4-(3-pyridylmethylideneamino)-1,2,4-tri- azin-3-one (46, pymetrozine, CGA-215944), is also considered as a promising insectoacaricide.This agent with contact and ingested modes of action is effective against both susceptible and resistant populations of aphids, noctuids and whiteflies at low usage rates and can be applied for protection of vegetables in field and greenhouse plantations. This compound exhibits the antifeedant activity thus violating the insect behavioural instincts. The convenient method of its industrial preparation is based on the reduction of a mixture of commercially available 4-amino-6- methyl-1,2,4-triazin-3-one and nicotinonitrile with hydrogen over Raney Ni.80 ± 82Novel insecticides and acaricides Me Me NC N N NNH2 + N N O O N NH NH N 46 (*99%) Ahigh insecticidal activity against a large variety of insects has been found for 3-(2-chloro-5-thiazolylmethyl)-4-nitroimino-5- methyl-2,3,5,6(2H,5H)-tetrahydro-1,3,5-oxadiazine (47, experi- mental insecticide CGA-293343).This agent possesses long- lasting residual activity. The mechanism of biological action of compound 47 resembles that of neonicotinoids.83 The method of preparation of this compound involves the alkylation of 3-methyl- 4-nitroiminotetrahydro-1,3,5-oxadiazine (48) with either 2-chloro-5-chloromethylthiazole or 5-chloromethyl-2-methyl- thiothiazole followed by the replacement of the methylthio group by chlorine.84 NNO2 NNO2 CH2Cl S S NMe N Cl HN NMe + Cl N N O 47 O48 NNO2 CH2Cl S S [Cl] NMe N 47 MeS 48+MeS N N O 2,4-Diaryl-1,3,4-oxadiazin-5-ones manifest high insectoacar- icidal activity.The study of the chemical structure ± biological activity relationship using the QSAR programme has shown that in a series of substituted oxadiazines the maximum biocidal activity falls on 4-(2-biphenylyl)-2-(2-tolyl)-1,3,4-(4H,6H)-oxa- diazin-5-one (49); its LC50 against mite Tetranichus telarius is equal to 25 mg litre71.85 C6H4Me-2 ON N O 49 C6H4Ph-2 Among derivatives of tetrazine, one can mention 3-(2-chloro- phenyl)-6-(2,6-difluorophenyl)-1,2,4,5-tetrazine (50, SZI-121) as an analogue of clofentezine. This compound at usage rates less than 80 g ha71 is effective for protection of fruit and citrus trees, vines and vegetables against fruit tree red spider mite Panonichus ulmi and spider mite Tetranichus sp.in their ovopositional and mobile stages of development. Compound 50 has translaminar and fumigated mode of action and long-lasting residual toxic- ity.86, 87 F Cl N N N N 50 F The most detailed study in a series of five- and six-membered sulfur-containing heterocycles has been accomplished for deriva- tives of substituted 1,2-dithiolanes and 1,3-dithianes. 2-Aryl-2- cyano-5-dimethylamino-1,3-dithianes 51 were synthesised by the reaction of 1,3-bis(arylsulfonylthio)-2-dimethylaminopropanes with CH-acids. These compounds possess high insecticidal activ- ity against rice green leaf hopper and spider mites.88 703 S Ar Ar SSO2Ar oxygenase B Me2N Me2N + S CN CN SSO2Ar 51 S Me2N S (O)n 52a,b n=0 (a), 1 (b).Dithianes 51 are converted into nereistoxin (52a) and its S-oxide 52b under the action of liver microsomal oxygenases and therefore they may be considered as propesticides. The nature of the aryl substituent in the 2-position strongly affects the capability of these compounds to penetrate through the covering tissues of insects.88 At the end of the 80's, guinesines A, B and C (53a ± c, respectively) were isolated from a Brazilian tree Cassiopourea guianensis, which showed fairly strong insecticidal properties.89 OH OH OH H H H H H H Me N Me N Me N S S S S53c S S53a 53b Modification of the molecules of guinesines resulted in a series of dialkylaminomethyl-1,2-dithiolanes, -1,2,3-trithianes and 2,2- disubstituted 4-dialkylaminomethyl-1,3-dithiane derivatives.Among these compounds, the activity of 3-dimethylamino- methyl-1,2-dithiolane (54) and cis-3,5- bis(dimethylaminomethyl)-1,2-dithiolane (55) was almost the same as that of nereistoxin (52a).88, 90, 91 NMe2 Me2N NMe2 S S S S54 55 5-Substituted 1,3-dithiane derivatives and their S-oxides 56a,b, 1,4-disubstituted 2,6,7-trithiabicyclo[2.2.2]octanes and their 2-oxides 57a,b, 1,4-disubstituted 2,6,7-trioxabicyclo[2.2.2]- octanes 58, 4-substituted 2,6,7-trioxa-1-phosphabicyclo- [2.2.2]octane 1-oxides and 1-sulfides 59a,b, chlorinated 2,3:8,7- endo-4,6-dioxatricyclo[7.2.1.02.8]dodec-10-enes 60 and 2,3:8,7- endo-4,6-dioxa-5-thiatricyclo[7.2.1.02.8]dodec-10-ene oxides 61 are competitive inhibitors of the GABA-controlled chloride channels in a nerve cell membrane and show insectoacaricidal activity.92 ± 97 O S S R2 R1 R R1 R2 (O)n (O)n OO 58 SS 57a,b S 56a,b n = 0 (a), 1 (b) (Cl)n (Cl)n O R X P O O O O OO 59a,b 60 S (O)m X = O (a), S (b) 61 m=0, 1 Substituents in the 5-position of compounds 56 and in the 4-position of compounds 57 ± 59 not only substantially determine the neurotoxicity of these substances, but are also essential for their biodegradability under the action of various oxygenases.Unfortunately, so far no commercial products among com- pounds 56 ± 61 have been developed.704 III.Natural compounds Considerable qualitative changes over the last decade have taken place in the use of insectoacaricides of the natural origin. Insecticides prepared on the basis of pyrethrum and derris- alkaloids have been employed on a small scale for certain purposes for already many decades. The same is true for the products obtained from the spore bacterium Bacillus thuringiensis, which are used against many types of leaf-eating insects and, primarily of all, against gypsy moth Lymantria dispar. All these preparations refer to the class of bioinsecticides, the total cost of their sales is estimated around $US 100 million. The use of the methods of molecular biology and of protein and peptide chemistry in the elucidation of the nature of the toxicity of these compounds has led to impressive results over the last decade.Here, only work directly related to the problem of plant protection against insects will be considered. The insecticidal action of biopreparations is based on the biocidal properties of a-, b-, g- and d-endotoxins of protein nature. All of them contain an active trypsin-resistant active center of molecular mass 65 kDa. The highest efficacy against insects was shown by d-endotoxin preparations of molecular mass 133 kDa. Different segments of this endotoxin are associated with its specific activities against different species of insects: the amino acid sequence 335 ± 450 is responsible for the activity against cabbage looper Trichoplusia ni, and the amino acid sequence 335 ± 615 is active against tobacco budworm Heliothis virescens.Achimerical toxin containing the amino acid sequence 450 ± 612 is 30 times more active against budworm H. Virescens than the natural d-endotoxin itself.98, 99 Selection of Bacillus thuringiensis has been carried out to manufacture standardised insecticidal preparations by microbio- logical methods. This was aimed at isolating clones that are highly productive with respect to the d-endotoxin. Fairly simple methods for the isolation of crystalline peptide and physicochemical procedures for the control of its quality have been developed. Based on crystalline d-endotoxin, the preparations `agree' and `novodor' are nowadays commercially available.To increase economic efficiency in manufacturing the prepa- rations based on d-endotoxin the latest achievements of genetic engineering have been successfully employed. The gene Cryl IA, which is responsible for production of d-endotoxin in Bacillus thuringiensis, was introduced into the gene of the bacterium Escherichia coli, which can be fairly easily cultivated. A mutant strain of E. coli has produced d-endotoxin for over 500 gener- ations without tearing away the gene implanted. d-Endotoxin obtained by the methods of genetic engineering is approved for use as a pesticide in the US forestry industry and for control of gypsy moth Lymantria dispar.100 Yet another approach to the protection of plants using the biocidal properties of endotoxins is based on the creation of transgenic plants which can produce endotoxins by themselves and, as a result, are resistant to pests.The implantation of the gene Cryl IA into gene apparatus of many crops, e.g., rice, tobacco, tomatoes and maize, enhances more than 100-fold their resistance. In the author's opinion, the most urgent task in this field of the research is the development of transgenic strains of potatoes resistant to Colorado beetle.101 ± 103 Nucleotide 62 (dibetha, turingiensin), which is a metabolite isolated from Bacillus thuringiensis, possesses high insecticidal activity. At usage rates of about 40 ± 60 g ha71, this is effective against Colorado beetle, ligus bud and phytophagous mites on cotton, potatoes and other crops.104 A F Grapov NH2 COOH N N HOCH H2C N (HO)2P(O)OCH N CH2OH O O O HOCH OHO CH OH OH 62 COOH Me Me O O O H MeNH Et O H H H Preparations based on macrolide antibiotics avermectin and ivermectin are mainly employed in livestock farming for control of endo- and exo-pests. Modification of avermectins or structurally similar milbemectins does not usually enhance the activity.105, 106 The only exception was the introduction of the methylamino group in the terminal oleandrosyl residue, which increased the insecticidal and acaricidal activities of semi-synthetic compound 63 more than by an order of the magnitude in comparison with the starting abamectin.107 OMeMe HO Me Me O Me O O OMe H OH O Me H OR 63 The mode of action of avermectins and the products of their modification is based on the inhibition of the GABA-receptors.Macrolides of the spinosine group, viz., spinosine A and D (64a and 64b, respectively), which were isolated from the micro- organism Saccharopolyspora spinosa, are of considerable interest. They manifest high insecticidal activity against many widespread pests and possess contact and ingested mode of action. The preparation `tracer' based on spinosines has good ecological and toxicological characteristics and is employed for protection of cotton.108 Me2N O O OOMe H H OMe OMe O O O O H H H 64a,b R R = H (a), Me (b). Promising results have been also obtained in the studies of insecticidal and acaricidal activities of roxaglamide and some of its analogues 65 ± 67, which were isolated from stems of the plant Aglaja roxburgiana.109, 110 CONMe2 HO MeO HOO MeO Ph C6H4OMe-4 65Novel insecticides and acaricides N N MeO HO O O Ph O O C6H4OMe-4 66 H OH MeO O NHCOCMe(Et)OH N O MeO Ph 67 Interestingly, the first analogue of organophosphorus insecti- cides has been recently found among natural compounds.Anti- biotic NK-901093 (68), which is an enol cyclophospate, was isolated from Streptomyces sp. At a concentration of 0.1 mg litre71, this compound causes 100% mortality in mosqui- toes and suppresses the activity of cholinesterase at concentrations four orders lower than that of malaoxon.111 O O O O P MeO O 68 IV. Pyrethroids and other compounds Recent years have been marked by the rapid rise in manufacture of pyrethroids, and the value of their sales has taken the first place among all types of insectoacaricides.Although it is worth mentioning that the real pyrethroid boom had already virtually abated in the 80's. In the 90's, the main emphasis in the research and manufacture of pyrethroids is made on the development of new technologies including the isolation of pure diastereomers and enantiomers for reduction of the usage rates of these compounds and minimisation of their impact on the environ- ment. Apart from that, much attention is paid to the development of numerous multicomponent preparation forms, including mix- tures, for their usage not only in farming but in the household, public health and industry.The scope of the synthetic works on pyrethroids over recent years was not so large. The most interesting result in this field was the synthesis of fluorine- and silicon-containing derivatives of previously known synthetic pyrethroids. In the case of the synthesis of fluorinated pyrethroids, the fluorine atoms and fluorine-containing groups were introduced in both the acidic part of the molecule and the aromatic ring to make these compounds more stable toward hydrolysis and the action of oxygenases. Among these compounds, phenothrin (69) and bioallethrin (70) analogues containing the difluoroisobutenyl group 112 and an analogue of cyfluthrin (71) bearing a difluorocy- clopropylidene moiety are worth mentioning.113 Me Me O OPh HF2C 69 O Me Me O HF2C O O 70 F F O Me Me O 71 Compound 71 causes 100% mortality in Spodoptera eridania, Aphis gossipii and Diabrotica undecimpunctata at concentrations of 0.6, 2.5 and 2.5 mg litre71, respectively.However, only two analogues of pyrethroids devoid of the ester group, viz., experimental insecticides flufenprox (72) and silafluofen (73), are of certain practical interest.114, 115 EtO CHCH2OCH2 CF3 72 Me EtO Si(CH2)3 Me 73 Flufenprox (72) has good economical and ecological charac- teristics, high insecticidal activity in doses of 75 ± 300 g ha71 against a broad range of pests, and is harmless for warm-blooded animals and bees.Silafluofen (73), which belongs to the group of silaneofans, is used against lepidopterans, dipterans, coleopterans, hemipterans, homopterans, etc., but is ineffective against aphids and whiteflies. Analogues of silafluofen (74) containing the difluorinated double bond possess the high insecticidal activity.116 F X Si F Me Me From the other groups of insectoacaricides, it is worth mentioning thiourea derivatives. Studies of the biological proper- ties of several hundreds of di-, tri- and tetra-substituted thioureas has led to the preparation diafenthiuron, 1-tert-butyl-3-(2,6- diisopropyl-4-phenoxyphenyl)thiourea 75. This is effective against sucking pests such as mites, aphids and whiteflies on cotton and vegetables.Upon UV irradiation or in vivo, compound 75 is converted into the corresponding carbodiimide 76.117, 118 It is the latter that acts as an insecticide. This intermediate blocks the activity of mitochondrial ATPase and therefore is classified as an oxidative phosphorylation decoupler.118 Pri S PhO NHCNHBut 75 Pri S Pri PhO Pri NBut N N N 77 S Pri NBut PhO N O Pri O 78 A number of other compounds were also synthesised, which are converted after elimination of a part of the molecule into carbodiimide 76. These are, for example, 1,4-disubstituted tetra- 705 FOPhOC6H4Cl-4 F OPh Y Z O 74 Pri hn PhO N C NBut 1O 76 Pri706 zoline-5-thione (77) and 3-thioxo-1,2,4-oxadiazol-5-one (78).Field tests for these compounds have also given good results.119 In the author's opinion, all these studies represent a fine illustration of a propesticidal approach to the development of novel insectoacaricides. In conclusion, some general tendencies in the manufacture and application of insectoacaricides should be noted. In 1996, the production of active principles of this group of insecticidal preparations had reached 680 000 tons with a total value of $US 8.7 billion. According to the forecast, in 2001 the value of the insecticide sales will reach 10.5 ± 10.7 billion dollars. These figures show that in the beginning of the XXIst century (the author assumes that in the near future) the programmes for control of harmful insect and phytophagous mites will be based on the use of the chemical preparations despite certain recent achievements in the development of biological methods for plant protection, first of all, in the selection of transgenetic plants resistant to pests.The portion of traditional preparations such as organophosphorus compounds, carbamates and pyrethroids will constitute not less than 80%± 85% of all manufactured insectoa- caricides. At the same time, the proportion of preparations with new modes of action will be gradually increased. 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ISSN:0036-021X    

出版商:RSC    

年代:1999

数据来源: RSC