摘要:

Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) Unusual strong broadening of some absorption bands in the IR spectra of organic molecules bonded with H+ in disolvates [L–H+–L] Evgenii S. Stoyanov G. K. Boreskov Institute of Catalysis, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russian Federation. Fax: +7 3832 34 3766; e-mail: stoyanov@catalysis.nsk.su An unusual feature has been detected in the IR spectra of the proton disolvates L–H+–L, namely strong broadening of the absorption bands of molecular groups of the organic ligand L directly bonded with H+.Broad absorption continua in the frequency range 200–3000 cm–1 and strong broadening of absorption bands are general unusual features of the IR spectra of proton hydrates in water and organic solutions.A number of theories explaining them by intrinsic properties of proton hydrates1–4 or by the effect of molecules in the nearest environment5,6 have been suggested. However, they cannot comprehend all known experimental data. The main structural unit of proton hydrates is the dihydrate [H2O–H+–OH2], that is the H5O2 + cation, or the monohydrate [H2O·H+·L1]·nL, where L1 is An– or an organic base7,8.Since both cations belong to the general class of homoconjugated L·H+·L and heteroconjugated L1·H+·L2 proton disolvates, a study of the IR spectra of different proton disolvates can give a new insight to the understanding of the IR spectra of proton hydrates. This paper presents data on unusual features in the IR spectra of disolvates of a strong acid [L·H+·L]·FeCl4 –, where L is acetone, butyl acetate (BA), tributyl phosphate (TBP), ethanol or diethyl ether in CCl4 solutions.All disolvates were obtained by passing dry gaseous HCl through 0.2 M FeCl3 solutions in CCl4 containing an organic base L in the molar ratio L/FeCl3 = = 2. The reaction HCl + FeCl3 + 2L®L2H+FeCl4 – results in the formation of an acid disolvate.The IR data shows that the solutions do not contain free ligand L, and FeCl3 is quantitatively transformed into FeCl4 – ions. Anhydrous reagents of the chemically pure grade were used. Organic bases were additionally purified to remove trace water by universally known methods. The solutions were prepared and poured into an IR cell in a dry box. The IR spectra were recorded on a Bruker IFS-113v FTIR spectrometer in the range 4000–200 cm–1 using a vacuum cell with silicon windows.The IR spectra of all disolvates contain very broad and intense bands of in-plane deformations d(OHO) ª 1500 cm–1 and antisymmetric stretching vibrations nas(OHO) ª 920 cm–1 of the central OH+O fragment with a very strong H-bond and a triply degenerate band n3(F2) at 383 cm–1 of tetrahedral FeCl4 – anions.The shape of the n3(F2) band is almost undistorted. This means that the degeneration is practically not removed because the FeCl4 – anion interacts with the L2H+ cation very weakly. The main distinctive feature of the IR spectra of L2H+ cations is an unusual behaviour of the absorption bands of the ligand atomic groups that are directly bonded with the proton H+.For instance, in the spectrum of (BA)2H+ cations there are no typical strong nas and ns bands of stretching vibrations of COO groups in butyl acetate molecules, but there is a very broad band at 1575 cm–1, which can be attributed to nas(COO) (Figure 1). Since this band is strongly overlapped with the others, its width at the half height can be estimated as � 65 cm–1.The band at 1304 cm–1, which slightly appears above the contour of the nas(OHO) and d(OHO) absorption bands, can be attributed to ns(COO). In the spectrum of (Me2CO)2H+ the intense narrow band n(C=O) is absent as well, while the n(C–C) band at 1250 cm–1 is shifted to the high-frequency region by 31 cm–1. This indicates that acetone molecules are bonded with H+ very strongly.Therefore, the frequency n(C=O) will be significantly lowered. There is only one band with a frequency of 1595 cm–1, which can be attributed to n(C=O),† but its width is unusually large (Figure 1, Table 1). There are all the known TBP bands in the IR spectrum of the (TBP)2H+ cation with the exception of the intense n(P=O) band (Figure 2). If the contour of the overlapped bands d(OHO) and nas(OHO) is separated into the two symmetric components d(OHO) = 1455 cm–1 and nas(OHO) = 920 cm–1 in order to describe the resulting shape correctly, a third component, a very broad and intense band at 1100 cm–1, should be added.Obviously, the latter should be attributed to the disappeared n(P=O) band. Despite the fact that the frequency and, especially, the half-width of this band (~190 cm–1) should be considered as approximate values, they are indicative of an unusually strong broadening.Indeed, if one compares the half-widths of n(P=O) bands of TBP molecules bonded to electron acceptors of different strengths (Table 1), one can see that a decrease of the n(P=O) frequency does not lead to a regular broadening of the bands with the exception of the symmetric hydroxonium ion in [H3O+·3TBP]FeCl4 –.For the latter, the nature of the broadening can be the same as that for the disolvate [H+·2TBP]FeCl4 –, but occurring less markedly. No significant broadening of the bands nas(COO) of butyl acetate and n(C=O) of acetone with decreasing frequency of the C=O group linked with the electron † The other narrow band at 1660 cm–1 has too low intensity.Furthermore, it is not sensitive to the addition of a small quantity of water; thus, it cannot be attributed to n(C=O) of the disolvate (Me2CO)2H+. Absorbance n/cm–1 2.5 2.0 1.5 1.0 0.5 1000 2000 3000 1595 1575 1304 n(C–C) 1250 n3(F2) Figure 1 IR spectra of carbon tetrachloride solutions of (BA)2H+FeCl4 – (solid line) and (Me2CO)2H+FeCl4 – (dotted line).The spectrum of CCl4 is subtracted. 0.6 0.4 0.2 0.0 Absorbance n/cm–1 1500 1000 1455 1100 920 Figure 2 IR spectrum of the [H+·2TBP]FeCl4 – disolvate. The bands d(OHO) = 1457 cm–1 and nas(OHO) = 920 cm–1 and the band at 1100 cm–1, which is attributed to ‘disappeared’ n(P=O), are marked by a dashed line.Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) acceptor is observed as well.It is only in the IR spectra of disolvates H+·2L that the broadening of the bands n(X=O) is so significant that it can be called anomalous. The bands of molecular group linked with H+ in H+·2L, which contain only single C–C and C–O bonds, are changed much more significantly since their oscillations strongly interact and are not characteristic. Thus, in the IR spectra of (Et2O)2H+ both the nas(C–O–C) band and the bands of stretching C–C vibrations are not observed.Similarly, the stretching C–O and C–C vibrations are not detected in the spectrum of (EtOH)2H+. However, the spectra of both of the disolvates contain the bands of stretching and bending vibrations of CH2 and Me groups. Thus, if L is bonded to H+ via an X=O group with a double bond whose vibrations interact weakly with those of coupled single bonds, as is the case, for example, in the disolvates (Bu–O–)3P=O–H+–… or (Me–)2C=O–H+–…, the n(X=O) band is broadened so significantly that it becomes difficult to detect it in the IR spectra. Meanwhile, the stretching vibrations of ordinary bonds coupled with the X=O group (P–O in TBP, C–C in acetone) are observed as bands of normal width. If L is linked with H+ via a molecular group containing only ordinary bonds, as is the case, for example, in (Me–CH2–)2O– H+–… of [Et2O·H+·Et2O] or in Me–CH2–O(H)–H+–… of [EtOH·H+·EtOH], not only the bands of stretching vibrations of the single bonds nearest to H+ (Cdash;O–C in Et2O or C–O in ethanol) but also the bands of C–C bonds coupled with them, are not observed in the IR spectra.The stretching OH vibration of the disolvate (EtOH)2H+, observed as a broad band at 3271 cm–1 is the only exception. The following explanation can be proposed for the unusual broadening of some absorption bands in the IR spectra of organic molecules L in the disolvates [LH+L] weakly perturbed by an anion. The potential energy curve of the proton in L2H+ has two minima with so low a barrier between them that it does not reach the energy of the ground vibration state.2–5,9 As a result, the minimum becomes broad and flat, and H+ in the ground vibrational state is delocalised in the spatial region A–B (Figure 3).If the rates of the H+ migration within this region and of the 0®1 vibration transition are comparable, for example, for a C=O group, the width of the n(C=O) band grows significantly.In other words, a fast change of the proton charge location within the A–B region induces similar changes in the electron density of the C=O bond. As a result, the force constant and the shape of the potential energy curve of the proton are changed with the same frequencies as the spatial location of the proton.This leads to the multiplicity of 0®1 (as well as 1®2, etc.) transition energies and to a significant broadening of the absorption bands. If the group linked with H+ is X=O with a highly characteristic frequency (weakly interacting with the frequencies of coupled single bonds), the modulating effect of H+ on the force constants of the bonds does not spread beyond the X=O bond.However, if the vibrations of a molecular group of the ligand L linked with H+ interact strongly with each other (the COO group, C–O–C and C–C vibrations, etc.), the specific influence of H+ is spread on the two nearest coupled bonds. In the proton dihydrate [H2O–H+–OH2]·nH2O, there is the same specific effect of a delocalised proton on the nearest O–H···O groups formed by the H5O2 + cation and water molecules.This may be a fundamental reason for the appearance of the main feature of the IR spectra of proton hydrates in aqueous and organic solutions and solids: strong broadening of the bands and extended absorption known as continuous background absorption. References 1 G. L. Hofacker, Y. Marechal and M. A. Ratner, in The Hydrogen Bond, eds. P. Schuster, G.Zundel and C. Sandorfy, North-Holland, Amsterdam, 1976, vol. 1, p. 295. 2 G. V. Yokhnevich and E. G. Tarakanova, J. Mol. Struct., 1988, 177, 495. 3 S. Bratos and H. Ratajczak, J. Chem. Phys., 1982, 73, 77. 4 H. Romanovski and L. Sobczyk, Chem. Phys., 1977, 19, 361. 5 G. Zundel, in The Hydrogen Bond, eds. P. Schuster, G. Zundel and C. Sandorfy, North-Holland, Amsterdam, 1976, vol. 2, p. 683. 6 N. B. Librovich, V. P. Sakun and V. D. Sokolov, in Vodorodnaya svyaz (The Hydrogen Bond), Nauka, Moscow, 1981, p. 174 (in Russian). 7 E. S. Stoyanov, J. Chem. Soc., Faraday Trans., 1997, 93, 4165. 8 E. S. Stoyanov, J. Chem. Soc., Faraday Trans., 1998, 94, 2803. 9 N. D. Sokolov, M. V. Vener and V. A. Savel’ev, J. Mol. Struct., 1988, 177, 93. 10 E. S. Stoyanov and L.V. Lastovka, Zh. Neorg. Khim., 1981, 26, 744 (Russ. J. Inorg. Chem., 1981, 26, 400). 11 E. S. Stoyanov, E. S. Mikhailov and I. I. Obraztsova, Koord. Khim., 1985, 11, 1663 (in Russian). 12 E. L. Smol’skaia, E. S. Stoyanov and N. L. Egutkin, Izv. Akad. Nauk SSSR, Ser. Khim., 1991, 593 (Bull. Acad. Sci., Div. Chem. Sci., 1991, 40, 514). aThe overlapped band of some non-equivalent P=O groups of TBP isomers.bH-complex of butyl acetate and p-nitrophenol. Table 1 The n(X=O) band frequencies and widths at the half height (Dn1/2) in the IR spectra of ‘free’ ligands L and ligands linked with electron acceptors. Compound Solvent or solution composition n(P=O)/cm–1 Dn(P=O)/cm–1 Dn1/2/cm–1 Reference TBP 100% TBP 1274a — 58b (TBP·2H2O)n 100% TBP, satur. with H2O 1248 26 42 10 [H5O2 +·2TBP·2H2O]FeCl4 – TBP 1218 56 22 8 [H3O+·3TBP]FeCl4 – TBP 1195 79 58 7 UO2Cl2·2TBP CCl4 1177 97 22 11 [H+·2TBP]FeCl4 – CCl4 1100 174 ~190 This work n(COO)/cm–1 Dn(COO)/cm–1 Dn1/2/cm–1 Butyl acetate 1.5 M in CCl4 1742 — 20 BA·p-NPb CCl4 1707 35 21 12 [H+·2BA]FeCl4 – CCl4 1575 167 �65 This work n(C=O)/cm–1 Dn(C=O)/cm–1 Dn1/2/cm–1 Acetone 0.8 M in CCl4 1718 — 13 [H+·nH2O·mMe2CO]FeCl4 – CCl4 1684 34 14 This work [H+·2Me2CO]FeCl4 – CCl4 1590 128 �94 This work O H O O HO A B D 4 3 2 1 0 Figure 3 The double minimum of the potential energy function of the bridged proton in the O–H+–O fragment of disolvates L2H+ is approached to a single broad and flat bottom. The proton in the ground state (u = 0) is delocalised within the A–B region. Received: 24th March 1999; Com. 99/

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年代:1999

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Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) Electrosynthesis of mixed tertiary phosphines catalysed by nickel complexes Yulia G. Budnikova,*a Yuri M. Karginb and Oleg G. Sinyashina a A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre, Russian Academy of Sciences, 420088 Kazan, Russian Federation. Fax: +7 8432 752253; e-mail:yulia@iopc.kcn.ru b Department of Chemistry, Kazan State University, 420008 Kazan, Russian Federation A versatile method for the synthesis of tertiary phosphines with aromatic and heteroaromatic substituents by cross-coupling of chlorophosphines and organic halides catalysed by Ni0 complexes of 2,2'-bipyridine was proposed.The development of new approaches to the synthesis of compounds with P–C bonds under mild conditions starting from white phosphorus and its derivatives is one of the most important subjects in organophosphorus chemistry.A particular attention has been given to the methods of preparation of tertiary phosphines including compounds with heteroatoms or functional groups in the molecule.1–3 These phosphines are of particular interest as potential ligands in water-soluble complexes of transition metals.Currently available chemical methods for the synthesis are based on the use of organometallic compounds, e.g., Grignard reagents or alkali metal phosphides.1–3 These methods are multistage and have some significant restrictions (low temperature and a considerable volume of a solvent), and the yields of desired products are not always high. It has been possible to synthesise only triaryl phosphines containing acceptor substituents (CN, COOMe etc.) in the aromatic ring only by reduction of appropriate phosphine oxides.3 An electrochemical approach can be used to design a versatile technique for the preparation of various types of tertiary phosphines. A procedure for the electrosynthesis of trialkyl and tribenzyl phosphines using soluble anodes was previously proposed.4 Unfortunately, this procedure is unsuitable for the synthesis of tertiary phosphines with aryl and, especially, heteroaromatic substituents attached to the phosphorus atom.The aim of this study was to develop a versatible method for the preparation of mixed tertiary phosphines on the basis of cross-coupling reactions of diphenylchloro- and phenyldichlorophosphines with aryl halides or C-halogen derivatives of sulfuror nitrogen-containing heterocycles catalysed by electrochemically generated Ni0 complexes.We decided on NiBr2bipy as the starting complex of NiII because of its greater reactivity as compared with coordinatively unsaturated nickel complexes we used previously.5,6 The reactions were carried out in an undivided cell equipped with a magnesium or zinc anode in the absence of a specially added supporting electrolyte.The use of soluble anodes, in some instances, makes it possible not only to simplify the electrochemical process significantly but also to control the direction of the reaction.7 The electrolysis was performed at a constant current density and room temperature until the concentration of the desired product in solution became constant.Mixed diphenylaryl phosphines 3 were isolated as a result of a cross-coupling reaction between diphenylchlorophosphine 1 with aryl bromides 2 under conditions of metallocomplex catalysis. The yields varied from 45 to 70% (Scheme 1) and were influenced by the nature of substituents in the aromatic ring and by the anode material.Note that a magnesium anode should be used for the synthesis of tertiary phosphines with donor substituents, and a zinc anode is recommended for the preparation of phosphines with acceptor substituents. Mixing of all reagents before the electrolysis also lowers the yield of desired product to 15–20%. Compounds 3 were purified by column chromatography.The structures were proved by NMR spectroscopy, and the composition was found by mass spectrometry.† We suppose that the first stage of a catalytic cycle is the electrochemical reduction of a NiII complex to a Ni0 complex. The latter is a catalyst of the reaction and can react with aryl bromide according to Scheme 2 with the formation of organonickel compound 4, which reacts with chlorophosphine 1 to form product 3 with the regeneration of the NiII complex.Model compound 5 was obtained to support the proposed scheme. This compound is the stable s-complex o-MeC6H4- NiBrbipy prepared by the electrochemical reduction of NiBr2bipy in the presence of the corresponding tolyl bromide at a potential of –1.2 V with reference to an SCE. The addition of chlorophosphine 1 to compound 5 leads to an instantaneous disappearance of the red colour and the development of a green colour of the solution, which is characteristic of NiII complexes.Diphenyl-o-tolylphosphine and a minor amount of its oxide were isolated from the reaction mixture. Nickel diphenylphosphide obtained by an analogous procedure does not react with aryl halides.Thus, this route can be excluded from the discussion of the cross-coupling reaction. Moreover, the experimental data can explain the fact that it is necessary to perform the process with continuous addition of chlorophosphine 1 to the reaction mixture in order to obtain tertiary phosphines 3 in high yields. The proposed method for the electrosynthesis of tertiary phosphines under conditions of metallocomplex catalysis is versatile and makes it possible to introduce a phosphine group into heterocyclic compounds like pyridine, thiophene, pyrimidine, Ph2PCl + ArBr Ph2PAr 1 2 3 NiBr2bipy/e– DMF Scheme 1 Ph2P CO2Et Ph2P CO2Et Ph2P CN 3b 3a 3c N Ph2P N Ph2P Ph2P N Ph2P S OMe 6d 6c 6b 6a N N Ph2P N N Ph2P Me Me Ph P N N 6e 6f 6g Ni2+bipy Ni0bipy ArNiBrbipy 3 2e 2 1 – NiBrClbipy Scheme 2 4Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) pyrazole and their derivatives under mild conditions.As a result of the cross-coupling reaction of corresponding C-halides with mono- and dichlorophosphines, a wide variety of mixed phosphines 6, which were not easily accessible, were obtained in high yields. Thus, we proposed a new versatile method for the one-step preparation of mixed tertiary phosphines containing both aryls with acceptor or donor groups in the aromatic rings and some heterocycles as substituents at the phosphorus atom under mild conditions.† Yields were calculated on a chlorophosphine basis. Zn and Mg anodes were used for preparation of compounds 3 and 6, respectively. NMR spectra were recorded for solutions in CDCl3. 3a: yield 63%. Mp 99–100 °C. 1H NMR, d: 7.19–7.34 (m, 10H), 7.43 (d, 2H), 7.77 (d, 2H), 4.25 (q, 2H, J 21.5 Hz), 1.27 (t, 3H, J 14.3 Hz). 13C NMR, d: 166.17 (s, COO), 143.70 (d, C–P, J 14.9 Hz), 136.05 (d, J 10.7 Hz), 133.97, 133.57, 133.17, 132.77, 131.77, 130.22, 129.17, 129.03, 128.95, 128.58, 128.43, 60.84, 14.16. 31P NMR, d: –6.7. Found (%): C, 75.34; H, 5.93; P, 9.28.Calc. for C21H19PO2 (%): C, 75.45; H, 5.69; P, 9.28. 3b: yield 66%. Mp 100–101 °C. 1H NMR, d: 7.89–7.99 (m, 12H), 7.12–7.34 (m, 12H), 4.22 (q, 2H, J 20.5 Hz), 1.23 (t, 3H, J 7.5 Hz). 13C NMR, d: 161.21 (s, COO), 138.19, 137.80, 137.49, 136.56, 136.35, 135.03, 134.55, 133.65 (d, J 19.5 Hz), 130.70, 130.55, 129.74, 128.88, 128.61, 128.74, 128.40, 60.95, 14.16. 31P NMR, d: –7.0. Found (%): C, 75.60; H, 5.80; P, 9.31. Calc. for C21H19PO2 (%): C, 75.45; H, 5.69; P, 9.28. 3c: yield 45%. Mp 97–98 °C (lit.,3 mp 96–98 °C). 1H NMR, d: 7.10– 7.80 (m). 13C NMR, d: 140.79 (d, J 17.1 Hz), 136.79, 136.09, 133.98, 133.14, 132.71, 132.15, 131.90, 130.77, 129.72, 129.49, 118.79 (s, CN), 112.98 (d, C–CN, J 6.0 Hz). 31P NMR, d: –6.0. 6a: yield 80%. Mp 81–83 °C (lit.,2 mp 82–84 °C). 1H NMR, d: 8.54– 8.57 (m, 1H), 7.15–7.34 (m, 10H), 6.90–6.98 (m, 2H). 13C NMR, d: 163.91 (d, J 4.1 Hz), 150.25 (d, J 12.5 Hz), 136.17 (J 10.5 Hz), 135.70, 134.32, 133.93, 129.03, 128.66, 128.52, 127.92, 127.62, 122.15. 31P NMR, d: –5.5. 6b: yield 63%. Mp 83–84 °C. 1H NMR, d: 8.53 (dd, 2H, J 4.40 Hz), 7.16–7.57 (m, 14H). 13C NMR, d: 154.28 (d, J 23.6 Hz), 149.72, 141.19, 104.87, 135.95, 135.75, 133.79 (d, J 19.7 Hz), 128.91, 128.76, 123.65, 123.57. 31P NMR, d: –13.5. 6c: yield 65%. Mp 42–43 °C (lit.,8 mp 44–46 °C). 1HNMR, d: 7.49 (d, 1H, J 4.5 Hz), 7.24–7.39 (m, 12H), 7.07 (t, 1H, J 4.5 Hz). 13C NMR, d: 137.96 (d, J 8.5 Hz), 136.33 (d, J 25.5 Hz), 133.93, 133.08 (d, J 19.6 Hz), 132.03, 128.68 (d, J 16.4 Hz), 128.38, 128.04 (d, J 7.9 Hz), 127.96. 31P NMR, d: –21.2. 6d: yield 66%. Mp 83 °C. 1H NMR, d: 7.24–7.36 (m, 6H), 7.18–7.22 (m, 7H), 3.63 (s, 3H). 13C NMR, d: 163.49, 153.52, 139.25, 138.12 (d, J 4.2 Hz), 136.78 (d, J 10.0 Hz), 134.29 (d, J 19.5 Hz), 128.94, 128.52, 128.37, 122.04, 121.62, 113.71, 53.20. 31P NMR, d: –4.98. 6e: yield 25%. Mp 74–75 °C (lit.,8 mp 75 °C). 1H NMR, d: 7.18–7.31 (m, 10H), 6.63 (s, 1H), 3.71 (s, 3H), 2.13 (s, 3H). 13C NMR, d: 152.41 (d, J 22.0 Hz), 135.50 (d, J 9.8 Hz), 133.20 (d, J 20.0 Hz), 136.92, 128.11, 128.31, 111.20 (d, J 6.1 Hz), 38.67, 37.23. 31P NMR, d: –33.1. 6f: yield 50%. Mp 118–119 °C. 1H NMR, d: 8.59 (d, 2H, J 4.87 Hz), 7.26–7.48 (m, 10H), 6.98–7.03 (m, 1H). 13C NMR, d: 156.49 (d, J 7.0 Hz), 134.58 (d, J 20.0 Hz), 129.24, 128.52, 128.37, 118.81. 31P NMR, d: –0.2. Found (%): C, 72.65; H, 4.98; P, 11.61; N, 10.21.Calc. for C16H13N2P: C, 72.73; H, 4.92; P, 11.74; N, 10.61. 6g: yield 68%. Mp 96–98 °C (lit.,8 mp 96 °C). 1H NMR, d: 7.06–7.18 (m, 4H), 7.29–7.31 (m, 3H), 7.39–7.54 (m, 4H), 8.63–8.70 (dd, 2H, J 4.7 Hz). 13C NMR, d: 150.34 (d, J 13.0 Hz), 135.45 (d, J 23 Hz), 134.80, 129.59, 128.85, 128.70, 128.55, 129.19, 122.46. 31P NMR, d: –4.0. References 1 D.C. Gilheany and C. M. Mitchell, in The Chemistry of Organophosphorus Compounds, ed. F. R. Hartley, John Wiley, New York, 1990, vol. 1, ch. 7, pp. 151–190. 2 G.R.Newkome, Chem. Rev., 1993, 93, 2067. 3 G. P. Schiemenz and H.-U. Siebeneick, Chem. Ber., 1969, 102, 1883. 4 J. C. Folest, J. Y. Nedelec and J. Perichon, Tetrahedron Lett., 1987, 17, 1885. 5 Yu. H. Budnikova and Yu. M. Kargin, Zh. Obshch. Khim., 1995, 65, 1660 (Russ. J. Gen. Chem., 1995, 65, 1520). 6 Yu. M. Kargin, V. V. Juikov, D. S. Fattakhova and Yu. H. Budnikova, Elektrokhimiya, 1992, 28, 615 (Russ. J. Electrochem., 1992, 28, 498). 7 J. Chassard, J. C. Folest, J. Y. Nedelec, J. Perichon, S. Sibille and M. Troupel, Synthesis, 1990, 369. 8 Dictionary of Organophosphorus Compounds, ed. R. S. Edmundson, Chapman and Hall, London, New York, 1987. RnPCl3 – n + R'–X RnPR3 – n NiBr2bipy/e– DMF 6 ' Scheme 3 Received: 22nd April 1999; Com. 99/1451

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年代:1999

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Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) Electroinduced oxidative transformation of 2,5-dioxabicyclo[4.4.0]decanes into 5-(1,3-dioxolan-2-yl)- and 5-(dimethoxymethyl)pentanoates Yuri N. Ogibin,* Alexander O. Terent’ev, Alexey I. Ilovaisky and Gennady I. Nikishin N. D. Zelinsky Institute of Organic Chemistry, Russsian Academy of Sciences, 117913 Moscow, Russian Federation.Fax: + 7 095 135 5328 Anodic oxidation of 2,5-dioxabicyclo[4.4.0]decane 1a, 1-methoxy-2,5-dioxabicyclo[4.4.0]decane 1b and 1-hydroxy-2,5-dioxabicyclo[ 4.4.0]decane 1c in methanol in the presence of tetrabutylammonium fluoroborate as a supporting electrolyte induces the electrooxidative transformation of substrates 1a and 1b into methyl 5-(dimethoxymethyl)pentanoate and of substrate 1c into methyl 5-(1,3-dioxolan-2-yl)pentanoate.Recently, we found the electroinduced oxidative rearrangement of 1,6-dimethoxy-2-oxabicyclo[n.4.0]alkanes into w-(2-methoxytetrahydrofur- 2-yl)alkanoates:1 This finding provoked us to investigate the behaviour of 2,5- dioxabicyclo[4.4.0]decane 1a, 1-methoxy-2,5-dioxabicyclo- [4.4.0]decane 1b and 1-hydroxy-2,5-dioxabicyclo[4.4.0]decane 1c under similar electrolysis conditions.† In this communication, we report the results obtained by the electrolysis.Methyl 5-(dimethoxymethyl)pentanoate 2 is formed as the main product from bicyclodecanes 1a and 1b in 75% yield, and methyl 5-(1,3- dioxolan-2-yl)pentanoate 3 is formed from bicyclodecane 1c in 90% yield (Scheme 1). The transformation of 1a–c into esters 2 and 3 resulted from the electrolysis of 1a–c at room temperature in methanol in the presence of tetrabutylammonium fluoroborate as a supporting electrolyte in an undivided cell equipped with a platinum or † Starting materials.trans-2,5-Dioxabicyclo[4.4.0]decane 1a2 was prepared from epoxycyclohexane by the acid-catalysed reaction with 2-chloroethanol followed by the treatment of the resulting 2-(b-chloroethoxy)- cyclohexanol with an alcoholic potassium hydroxide solution (60% overall yield). 1-Methoxy-2,5-dioxabicyclo[4.4.0]decane 1b3 was the product of the acid-catalysed addition of methanol to 2,5-dioxabicyclo- [4.4.0]dec-1(6)-ene.4 1-Hydroxy-2,5-dioxabicyclo[4.4.0]decane 1c was synthesised by a known procedure4 from cyclohexanone in 40% yield; ethylene ketal of 2-hydroxycyclohexanone was formed along with 1c in the same yield.graphite anode and a stainless steel cathode under passages of 2–4 F mol–1 of electricity (Table 1).‡ The structures of esters 2 and 3 were established on the basis of 1H and 13C NMR spectra,§ which contained signals due to dimethoxymethyl (dH 3.28, 4.31; dC 52.5, 64.7 and 104.1), methoxycarbonyl (dH 3.63; dC 51.3, 173.8) and 1,3-dioxolanyl (dH 3.87, 4.81) groups, and by comparison of their hydrolysis product with the authentic methyl 6-oxohexanoate.6 The formation of two types of products from structurally similar starting substrates indicates a difference in the mechanisms of their electrochemical transformations.A rearrangement related to that observed for 1,6-dimethoxy-2-oxabicyclo[n.4.0]alkanes,1 occurs only in the case of bicyclodecane 1c.The electrolysis of bicyclodecanes 1a and 1b gives ester 2 and is not accompanied by the rearrangement. Ester 2 is formed from substrate 1a through the intermediate formation of bicyclodecane 1b. Scheme 2 illustrates the proposed mechanism for the transformation of substrates 1a–c into esters 2 and 3. The electrochemical process begins with electron transfer from electrophorus ethylenedioxy fragments of bicyclodecanes 1a–c.It is possible by two routes of further transformation of the resulting radical cations; one route starts with the deprotonation of radical cations and the formation of radicals A (route i), and the other route starts with the cleavage of the bridgehead C–C bond and the formation of distonic radical cation8 B (route ii). Similar radical cations also arise from subsequent electrochemical transformations of radicals A.The transformations of radical cations derived from bicyclodecanes 1a and 1b,c follow routes i and ii, respectively. The conversion of distonic ions B (X = OH) electrogenerated from substrate 1c into the final product (ester 3) is accompanied by the deprotonation, rearrangement and decyclization via oxonium ions F.¶ ‡ Electrolysis of dioxabicycloalkanes 1a–c (typical procedure).A solution of an electrolyte (9 mmol), compound 1 (5 mmol) and n-decane (internal standard, 3 mmol) in MeOH (15–25 ml) was placed in an undivided cell5 and then electrolysed at a constant current (0.5 A) and room temperature under intense stirring until more than 90% of 1 was converted.The solvent was removed, the residue was extracted with hexane (2×20 ml), and the combined extracts were concentrated. The products were isolated by vacuum distillation or flash chromathography with hexane–ethyl acetate (1%) as an eluent and then analysed. § 1-Methoxy-2,5-dioxabicyclo[4.4.0]decane 1b.3 1H NMR (200MHz, CDCl3) d: 1.55–1.80 (m, 8H, CH2), 3.23 (s, 3H, MeO), 3.30 (m, 1H, CH), 3.46 and 3.82 (m, 4H, OCH2CH2O). 13C NMR (50 MHz, CDCl3) d: 96.4 (O–C–O), 80.8 (CH–O), 64.8, 60.2 (O–C–C–O), 46.9 (MeO), 29.82, 27.96, 24.18, 21.82 (CH2). Methyl 5-(dimethoxymethyl)pentanoate 2.6 1H NMR (200 MHz, CDCl3) d: 1.35 (m, 2H, CH2), 1.60 (m, 4H, CH2), 2.30 (t, 2H, CH2COO), 3.28 (s, 6H, OMe), 3.63 (s, 3H, MeOCO), 4.31 (t, 1H, CHOMe). 13C NMR (50 MHz, CDCl3) d: 178.8 (O=C–O), 104.1 (O–CH–O), 64.7, 52.5, 51.3 (OMe), 33.8, 32.8, 24.6, 24.0 (CH2). Methyl 5-(1,3-dioxolan-2-yl)pentanoate 3.7 1H NMR (200 MHz, CDCl3) d: 1.42–1.63 (m, 6H, CH2), 2.30 (t, 2H, CH2COO, J 7.5 Hz), 3.63 (s, 3H, MeO), 3.87 (m, 4H, OCH2CH2O), 4.81 (t, 1H, OCHO, J 4.9 Hz). ¶ The participation of cyclic oxonium ions in the isomerization of linear aliphatic methoxy-substituted carbonium ions was found in ref. 9. O (CH2)n OMe OMe 1 2 3 4 5 6 – e, MeOH O COOMe OMe n O O (CH2)4 X O O COOMe 4 OMe MeO COOMe – e, MeOH X = H, OMe X = OH 4 1a–c a X = H b X = OMe c X = OH 2 3 O H COOMe 4 4 Scheme 1 H3O+ H3O+Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) A gain in energy as a result of decyclization of the strained 10-membered ring system seems to be a driving force for this process.Distonic ions B (X = OMe) derived from substrates 1a and 1b are likely to be turned to the final product (ester 2) as a result of simultaneously occurring electrooxidation and alcoholysis of radical and cationic centres and by the interaction of cationic intermediates D and cyclic ortho ether 5 with methanol.The protons generated during the electrooxidation of methanol and the alcoholysis of intermediates B and D are a possible catalyst for the reaction of this ortho ether with methanol. The reduction of the protons at a cathode to produce molecular hydrogen does not permit them to be accumulated in the electrolysis products in a concentration sufficient for catalysing the complete conversion of the ortho ether into ester 2.This was supported by the presence of signals typical of protons of the methoxy group (dH 3.13) and 13C nuclei (dC 115.5) of the ortho ether group10 in the NMR spectra of the electrolysis products of 1a. Thus, the electroinduced oxidative rearrangement of 2-oxaand 2,5-dioxabicycloalkanes is not a general case, and it is typical of only a limited range of compounds of this kind, such as 1,6-dimethoxy-2-oxabicyclo[n.4.0]alkanes and 1-hydroxy-2,5- dioxabicyclo[4.4.0]decane.This work was supported by the Russian Foundation for Basic Reseach (grant no. 97-03-33159). References 1 Yu. N. Ogibin, A. O. Terent’ev, A. I. Ilovaisky and G. I. Nikishin, Mendeleev Commun., 1998, 239. 2 F. R. Larsen and A. Neese, J.Am. Chem. Soc., 1975, 97, 4345. 3 D. Lalandais, C. Baequet and J. Einhorn, Tetrahedron, 1981, 37, 3131. 4 I. R. Fjeldskaar, P. Rongved and L. Skattebol, Acta Chem. Scand., 1987, B41, 477. 5 Yu. N. Ogibin, A. I. Ilovaisky and G. I. Nikishin, Izv. Akad. Nauk, Ser. Khim., 1994, 1624 (Russ. Chem. Bull., 1994, 43, 1536). 6 G. A. Tolstikov, M. S. Miftakhov, F. A. Valeev, R. R.Akhmetvaleev, L. M. Khalilov and A. A. Panasenko, Zh. Org. Khim., 1985, 21, 72 [J. Org. Chem. USSR (Engl. Transl.), 1985, 21, 65]. 7 T. Nakamura, H. Sawada and M. Nakayma, Jpn. Kokai Tokyo Koho, Japanese Patent 02 48.585 (90 48.585), 1991 (Chem. Abstr., 1991, 113, P 41219). 8 K. M. Stirk, L. K. Kiminkinen and H. I. Kenttamaa, Chem. Rev., 1992, 92, 1649. 9 (a) E. L. Allred and S. Winstein, J.Am. Chem. Soc., 1967, 89, 3991; (b) E. L. Allred and S. Winstein, J. Am. Chem. Soc., 1967, 89, 4012. 10 (a) P. Deslongchamps, J. Lessard and Y. Nadeau, Can. J. Chem., 1985, 63, 2485; (b) P. Deslongchamps, J. Lessard and Y. Nadeau, Can. J. Chem., 1985, 63, 2493. O O (CH2)4 i (X = H) – H+ 1a–c – e 1a–c O O (CH2)4 MeO A – e, MeOH 1b O O (CH2)4 B X MeOH – e O O (CH2)4 MeO 5 O O (CH2)4 D MeO OMe OMe X = OMe – H+ – e, MeOH OMe O O (CH2)4 C O – H+ X = OH 2 MeOH OMe (CH2)4 G O (CH2)4 F O O (CH2)4 E O 3 – e O O OH O O Scheme 2 – H+ ii X = OMe, OH – H+ aOn a converted bicyclodecane basis. Table 1 Electroinduced transformation of 2,5-dioxabicyclo[4.4.0]decane 1a, 1-methoxy-2,5-dioxabicyclo[4.4.0]decane 1b, and 1-hydroxy-2,5- dioxabicyclo[4.4.0]decane 1c to methyl 5-(dimethoxymethyl)pentanoate 2 and methyl 5-(1,3-dioxalan-2-yl)pentanoate 3. Entry Bicycloalkane Anode Q/F mol–1 Conversion (%) Product Yield (%)a 1 1a Pt 2.0 85 1b + 2 50 + 28 2 1a Pt 3.0 95 1b + 2a 34 + 44 3 1a Pt 4.0 100 1b + 2a 23 + 57 4 1b Pt 2.0 90 2 80 5 1c C 4.0 100 3 90 Received: 12th March 1999; Com. 99/1460

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Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) Catalysis of the hydrolysis of phosphorus acids esters by the mixed micelles of long-chain amines and cetylpyridinium bromide Alla B. Mirgorodskaya,*a Lyudmila A. Kudryavtseva,a Yuri F. Zuev,b Victor P. Archipovc and Zyamil Sh. Idiyatullinc a A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre, Russian Academy of Sciences, 420088 Kazan, Russian Federation.Fax: +7 8432 75 2253; e-mail: vos@iopc.kcn.ru b Kazan Institute of Biochemistry and Biophysics, Kazan Scientific Centre, Russian Academy of Sciences, 420503 Kazan, Russian Federation c Kazan State Technological University, 420015 Kazan, Russian Federation Self-association of long-chain amines and formation of mixed micelles, including cetylpyridinium bromide, influence the rate and the direction of the O,O-(bis-p-nitrophenyl)methylphosphonate hydrolysis; characteristic parameters of the micellar aggregates have been obtained by kinetic methods and 1H NMR spectroscopy.The ability of long-chain amines to self-associate leads to essential changes in their basicity and nucleophilicity compared with short-chain analogues.1–3 In the presence of surfactants, long-chain amines form mixed micelles which have some quite new properties.4,5 The influence of the mixed micelles formation in the presence of amines on their reactivity has not been practically studied up to now.The main goal of this work was to investigate the catalytic activity of primary long-chain n-alkylamines in water and aqueous solutions of cetylpyridinium bromide (CPB).For this purpose, the kinetics of hydrolysis of O,O-(bis-p-nitrophenyl)- methylphosphonate 1 has been studied, and a set of characteristic parameters of the mixed micelles formed in the systems have been obtained by independent physical techniques. Esters of phosphorus acids in the presence of amines in aqueous solutions undergo alkaline hydrolysis as well as hydrolysis due to the general base mechanism3,6 The contribution of the aminolysis in the case of primary amines is rather small.3,7 The effect of the general base catalysis in aqueous solutions is proportional to the basicity of the nucleophile.The dependence of the observed rate constants (kobs) on the concentration of hydrophilic short-chain amines is linear in a rather wide range.3 In the case of amines with hydrophobic radicals, the process becomes more complicated because of aggregation phenomena.The kinetics of hydrolysis of 1 in aqueous solutions of partially protonated decylamine or octylamine as monitored under pseudo-first-order conditions by optical spectroscopy based on an increase in the absorbance due to the liberation of p-nitrophenolate (l = 400 nm).The dependence of the rate constants on the concentration of decylamine (CDA) reflects changes in the system under study (Figure 1, curve 4). The first linear portion corresponds to a pre-micellar state. The changes in the curvature of kobs = f(CDA) are connected with micelles formation. The plateau is due to saturation of the micelles by substrate molecules.The linearity of the dependences of kobs on the octylamine concentration up to 0.015 mol dm–3 (pH 9.4–10.4) gives evidence of the absense of octylamine associates in this range. The bimolecular rate constant (k2) is equal to 0.7 dm3 mol–1 s–1. The fact of micelle formation by long-chain amines has been confirmed by measuring the surface tension of aqueous solutions.The values of the critical micelle concentration (CMC) for decylamine are essentially lower as compared with octylamine (for example, in the point of half-protonization, the CMC values at 20 °C are 0.0013 mol dm–3 for decylamine and 0.010 mol dm–3 for octylamine). The CMC data confirm that the conditions of our kinetic experiments in the case of octylamine correspond to the pre-micellar range, whereas for decylamine they cover the range of the micelle formation.This is reflected in the specific pattern of the dependence of kobs on the amine concentration. MeP(O)(OC6H4NO2-p)2 MeP(O)(OC6H4NO2-p)OH 1 + OH– + H2O(RNH2) – –OC6H4NO2-p – HOC6H4NO2-p 0.12 0.10 0.08 0.06 0.04 0.02 0.00 0.000 0.005 0.010 0.015 kobs /s–1 CDA/mol dm–3 1 2 3 4 Figure 1 Observed rate constants for the hydrolysis of 1 as functions of decylamine concentration (25 °C).(1) CCPB = 0.05 and (2) 0.02 mol dm–3 at varied pH; (3) CCPB = 0.015 mol dm–3 at pH 9.4; (4) CCPB = 0 at pH 9.4. aFor CPB in aqueous solutions, the CMC is equal to 0.0006 mol dm–3.18 bk'0 is the constant of alkaline hydrolysis at pH 9.4 in the absence of CPB. cIn the absence of CPB at pH 9.4, for decylamine: Kbond = 46 mol–1 dm3, CMC = 0.001 mol dm–3 and km = 0.21 s–1.dIn a dilute NaOH solution. Table 1 Micellar parameters for the hydrolysis of 1 in CPB solutions in the presence of primary n-alkylamines (25 °C). Amine C/mol dm–3 pH Kbond / dm3 mol–1 CMCa/ mol dm–3 km/s–1 km/k'0 b Octylamine 0.0025 9.4 195 0.00012 0.031 77 0.005 9.4 267 0.00021 0.033 82 0.01 9.4 364 0.00012 0.039 96 0.02 9.4 350 0.00010 0.041 98 Decylaminec 0.001 9.4 80 0.00010 0.060 150 0.0018 9.4 92 0.000098 0.083 206 0.0025 9.4 87 0.00007 0.12 300 OH–d 10.4 330 0.00060 0.20Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) In the decomposition of 1 in aqueous solutions in the presence of CPB and a long-chain amine, one can expect the acceleration of alkaline hydrolysis as well as of the process catalysed by the general base mechanism.First of all, it is induced by solubilization of the substrate and the amine by micelles because of hydrophilic interactions. Hydroxide ions are also concentrated at the positively charged micellar surface due to electrostatic attraction. This concentration of reagents in the micellar pseudophase, which in turn is accompanied by changes in the microenvironment, solvation and orientation of reacting species, is the reason of micellar catalytic effects observed in aqueous surfactant solutions.8–10 The influence of CPB on the hydrolysis rate of 1 (Figure 1, curves 1–3) with increasing quantities of decylamine is related to an increase in the pH of solutions (from 9 up to 11) as well as to an increase in the concentration of the nucleophile.The latter ‘activates’ water molecules which participate in the degradation of ester bonds. To estimate the influence of amines on the rate of the process, the kinetic experiment should be performed at fixed pH values, which were attained by adding HCl. The relationship obtained for the hydrolysis of 1 in the presence of octylamine in an aqueous solution of CPB at pH 9.4 was slightly changed by varying the amine concentration in the reaction media (Figure 2).This is evidence of the alkaline hydrolysis prevalence under the mentioned conditions. The amine acts here only as a buffer. At the same time, the rate of hydrolysis of 1 in the micellar solution of CPB in the case of decylamine significantly depends on the amine concentration (Figure 2).This allows us to assume that decylamine acts not only as a buffer but also as a general base catalyst. The data were analysed in terms of the pseudophase model of micellar catalysis,8,9 which was successfully used for mixed micelles,11,12 by the equation: where k0 and km are the rate constants in aqueous and micellar phases, respectively, Kbond is the reduced binding constant of the substrate, Cdet is the concentration of the detergent minus CMC.As one can see in Table 1, hydrophobic amines enhance the micelle formation of CPB and reduce the CMC values. This is characteristic of the formation of mixed aggregates.13 The effect of amines on the substrate bonding is more significant in the presence of decylamine and reflects the decrease of Kbond.Nevertheless, the efficiency of the micellar catalysis (km/k'0) in the hydrolysis process of 1 in CPB solutions is higher in the case of decylamine as compared with octylamine (Table 1). This is due to the increasing contribution of general base catalysis. Thus, the peculiarities of the decylamine kinetic behaviour in the presence of CPB can be explained by the formation of mixed micelles in these systems.We tried to confirm the kinetic data by 1H NMR spectroscopy with the Fourier transform and pulsedgradient spin echo (FT-PGSE). This technique allowed us not only to obtain the spectra of chemical ingredients of micellar systems but also to determine the self-diffusion coefficients (D) of the components.14,15 The self-diffusion measurements were performed using a modified TESLA-BS 576A NMR spectrometer (100 MHz) equipped with home-built field-gradient units producing a field gradient up to 50 G cm–1, according to the procedure described earlier.14 Water used for the NMR experiments was prepared from 95% (v/v) of deuterium oxide (Ferak) and 5% of twice-distilled water; the concentration of CPB was 0.05 mol dm–3.The self-diffusion data and the results of calculation are presented in Table 2. The lines from the (–CH2–)n groups of CPB and decylamine (1.2 ppm) and from water (4.78 ppm) are most suitable for selfdiffusion measurements in 1H NMR spectra. The diffusive decay of the methylene line cannot be divided into the fractions from CPB and decylamine.It is very difficult to imagine that two substances which differ in molecular weight and micelle-forming properties diffuse equally. We can suppose that both CPB and decylamine move as components of a single structural aggregate. Using the modified Stokes–Einstein equation,16 we estimated (see Table 2) the effective micelle radius R as where f is the volume fraction of the dispersed phase and h = = 1.033 N s m–2 is taken equal to the viscosity of D2O at 30 °C.Up to a certain concentration of decylamine, one can see only a little increase of the aggregates effective radius as compared with the pure CPB system (mole fraction XDA = 0). When the molar ratio between CPB and decylamine is approximately 3:1, the aggregate size is dramatically increased, or changes in the micelle shape from spheroid to cylinder occur.Another confirmation of the formation of mixed micelles is broadening of all lines in the NMR spectra except that of water when decylamine is added to the CPB solution (Table 2). The increase in the line width (Df1/2) indicates that there is a reduction in the intramicelle molecular motion17 as a result of penetration of decylamine into the CPB micelles.Hence, by means of the kinetic method and 1H NMR spectroscopy, the existence of mixed micelles formed by decylamine and CPB was confirmed. Their catalytic properties as well as the influence on the mechanism of hydrolytic decomposition of phosphorus acid esters were estimated. Several characteristic parameters of mixed aggregates such as critical micelle concentrations, self-diffusion coefficients and effective hydrodynamic radii of mixed micelles were obtained. 0.06 0.05 0.04 0.03 0.02 0.01 0.00 0.000 0.004 0.008 0.012 kobs /s–1 CCPB/mol dm–3 1 2 3 4 5 6 Figure 2 Observed rate constants for the hydrolysis of 1 in the presence of n-alkylamines (pH 9.4, 25 °C) as functions of CPB concentration. Decylamine CDA = (1) 0.0025, (2) 0.0018 and (6) 0.001 mol dm–3; octylamine COA = (3) 0.02, (4) 0.005 and (5) 0.0025 mol dm–3.kobs= , km Kb ondCdet + k0 1 + KbondCdet (1) aMeasurements were performed at 30±0.5 °C, the accuracy of measurements is £ 4%. bCCPB = 0.05 mol dm–3, (the concentration of CPB in the experiments remained constant). cThe width of the (–CH2–)n line (1.2 ppm). Table 2 Parameters of the mixed micelles, measured by 1H NMR spectroscopya at different ratios between CPBb and decylamine (XCPB + XDA = 1).XDA D/10–11 m2 s–1 Rm/Å Df c 1/2/Hz 0.0 5.15 42.1 4.8 0.091 5.11 43.1 5.5 0.169 4.99 44.1 7.0 0.219 4.95 44.3 9.8 0.306 4.04 54.2 12.0 0.338 2.97 73.7 14.0 0.389 2.61 83.6 16.5 0.656 1.50 125.0 R = (1 – 2f)kT/6phD, (2)Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) This work was supported by the Russian Foundation for Basic Research (grant no. 99-03-32037a). References 1 V. C. Pshezhetsky and A. P. Luk’yanova, Bioorg. Khim., 1976, 2, 110 [Sov. J. Bioorg. Chem. (Engl. Transl.), 1976, 2, 85]. 2 J. R. Knowles and C. L. Parsons, J. Chem. Soc., Chem. Commun., 1967, 755. 3 R. F. Bakeeva, L. A. Kudryavtseva, V. E. Bel’sky, S. B. Fedorov and B.E. Ivanov, Izv. Akad. Nauk SSSR, Ser. Khim., 1983, 1429 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1983, 32, 1297). 4 A. B. Mirgorodskaya, L. A. Kudryavtseva and B. E. Ivanov, Izv. Akad. Nauk, Ser. Khim., 1996, 336 (Russ. Chem. Bull., 1996, 45, 351). 5 A. B. Mirgorodskaya, L. A. Kudryavtseva, L. Ya. Zakharova and V. E. Bel’sky, Izv. Akad. Nauk, Ser. Khim., 1998, 1333 (Russ.Chem. Bull., 1998, 47, 1296). 6 H. J. Brass and M. L. Bender, J. Am. Chem. Soc., 1972, 94, 7421. 7 V. E. Bel’sky, F. G. Valeeva and L. A. Kudryavtseva, Izv. Akad. Nauk, Ser. Khim., 1998, 1339 (Russ. Chem. Bull., 1998, 47, 1302). 8 F. M. Menger and C. E. Portnoy, J. Am. Chem. Soc., 1967, 89, 4698. 9 C. A. Bunton, Adv. Chem. Soc., 1987, 425. 10 C. A. Bunton and G. Savelli, Adv. Phys. Org. Chem., 1986, 22, 213. 11 H. J. Foroudian, C. A. Bunton, P. M. Holland and F. Nome, J. Chem. Soc., Perkin Trans. 2, 1996, 557. 12 S. J. Froehner, F. Nome, D. Zanette and C. A. Bunton, J. Chem. Soc., Perkin Trans. 2, 1996, 673. 13 L. Huang and P. Somasundaran, Langmuir, 1996, 12, 5790. 14 B. Lindman, P. Stilbs and M. E. Moseley, J. Colloid Interface Sci., 1981, 83, 569. 15 V. D. Fedotov, Yu. F. Zuev, V. P. Archipov, Z. Sh. Idiyatullin and N. Garti, Colloids Surf., 1997, 128, 39. 16 H. N. W. Lekkerkerker and J. K. G. Dhont, J. Chem. Phys., 1984, 80, 5790. 17 Kh. M. Aleksandrovich, L. V. Dikhtievskaya, T. D. Mitina, S. A. Prodan and E. F. Korshuk, Kolloidn. Zh., 1990, 52, 835 [Colloid J. USSR (Engl. Transl.), 1990, 52, 725]. 18 Poverkhnostno-aktivnye veshchestva: Spravochnik (Surfactants: Handbook), eds. A. A. Abramson and G. M. Gaevoi, Khimiya, Leningrad, 1979, p. 376 (in Russian). Received: 2nd March 1999; Com. 99/1454

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Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) The first efficient electrophilic carbonylation of ethane with carbon monoxide Alexander V. Orlinkov,* Irena S. Akhrem and Sergei V. Vitt A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 117813 Moscow, Russian Federation. Fax: +7 095 135 5085; e-mail: cmoc@ineos.ac.ru Ethane reacts with CO without solvent in the presence of polyhalomethane·2AlBr3 superelectrophilic systems to form EtCOOR after alcoholysis together with small amounts of corresponding esters of 1- and 2-bromopropanoic acids.Ethane is the second alkane to methane in both inertness and abundance in natural gas. Therefore, the development of direct methods for ethane functionalization is one of the most important problems in the chemistry of alkanes.Among the numerous examples of electrophilic carbonylation of saturated hydrocarbons (mainly by HX–AlCl3 at elevated temperature and pressure with protic superacids under ambient conditions), only a very limited number of selective reactions have been described (see refs. 1–6 and references therein). These are reactions of propane (in the presence of polyhalomethane- containing promotors)3 and carbonylation of C5–C6 7 cycloalkanes, all in HF–SbF5 media.The polyhalomethane-based superelectrophilic systems were found to be good initiators for selective carbonylation of propane,8 butane and pentane,9 as well as C5–C6 10 cycloalkanes in organic media. These reactions occur probably via the Koch–Haaf mechanism involving the generation of carbocations followed by CO trapping to give acylium cations.11 The electrophilic carbonylation of ethane has not been reported earlier.On the contrary, catalytic carbonylation of methane, ethane, propane (nonselective) and cyclohexane in CF3COOH in the presence of a Pd(OAc)2 + CuCl2 mixture and K2S2O8 as an oxidant was performed.12 These reactions were carried out at 80 °C for 20 h and required large amounts of K2S2O8 and CF3COOH.For example, 100 g of Pd(OAc)2, 150 g of Cu(OAc)2, 8 kg of K2S2O8 and 17 dm3 of trifluoroacetic acid are needed to obtain 1 kg of EtCOOH.12 We report the first example of the efficient electrophilic carbonylation of ethane with CO. At 50 °C, ethane reacts with CO in the presence of polyhalomethane–AlBr3 superelectrophilic systems to form EtCOOBu 1 after treatment of the reaction mixture with n-butanol (Scheme 1).† With CBr4·2AlBr3 superacid as a promoter, the yield of 1 is 86% on a superelectrophile basis after 2 h (Table 1).In addition, esters 2 and 3 of 1- and 2-bromopropanoic acids are formed as by-products. The overall yields of ethane carbonylation products 1–3 are close to quantitative values with respect to the superelectrophile.Interestingly, under similar conditions, 50–60% yields of 1 can be achieved using CCl4·3AlBr3 and CHCl3·3AlBr3, † General procedure. To form a homogeneous liquid system, a mixture of appropriate amounts of AlBr3 and a polyhalomethane was heated and stirred without solvent in a 50 ml stainless steel autoclave (Parr Instrument Co.) at 80 °C for 5 min.After cooling to 50 °C, ethane and CO were supplied to the autoclave, and the reaction mixture was heated and stirred at 50 °C. After completion of the reaction, n-butanol was added at room temperature. The resulting mixture was poured into water, extracted, washed, dried and analysed by GC and GC–MS. while AlBr3 in CH2Br2 is completely inactive.In the case of CHCl3·3AlBr3, the ethane carbonylation occurs with a very high selectivity, although the yield of 1 is lower. The yields of 1 in the presence of the CBr4·2AlBr3 system strongly depend on temperature and the CO/C2H6 ratio (m). Higher yields of 1 were obtained at 50 °C. On going from m = 1 to m = 2.2, the yields of 1 considerably increase, while they fall down at m = 3 (Table 1).The yields and selectivities of formation of 1 also decrease on going from the hardest CBr4·2AlBr3 system to the milder CCl4·3AlBr3 and CHCl3·3AlBr3 systems. The proposed scheme of the ethane carbonylation involves generation of the ethyl cation followed by CO trapping to form the EtCO+ cation and, finally, EtCOOR 1 (Scheme 2). An increase in both the superelectrophile strenght and the CO/C2H6 ratio (within a certain range) is favourable to the generation of the ethyl cation and its addition to a CO molecule. For elucidation of the mechanism of formation of bromine-containing products 2 and 3, a further study is required.Thus, the new superelectrophilic systems allowed us to perform the efficient one-pot functionalization of ethane, which is an inert alkane.This work was supported by the Russian Foundation for Basic Research (grant nos. 97-03-32986, 96-15-97341 and 99-03-30006) and the U.S. Civilian Research & Development Foundation (grant no. RC1-274). C2H6 + CO COOBu COOBu COOBu Br Br i, E, 50 °C, 2 h ii, BuOH 1 2 3 E = CBr4·2AlBr3, CCl4·3AlBr3, CHCl3·3AlBr3 Scheme 1 aThe reactions were carried out at 65 °C. Table 1 Carbonylation of ethane with CO initiated by polyhalomethanebased superelectrophiles (E) at 50 °C.Run E PCO PC2H6 CO:C2H6:E t/h Products (mol%) 1 2 3 1a CBr4·2AlBr3 20 20 1:1:0.05 3 35 6 6 2a CBr4·2AlBr3 45 20 2.2:1:0.05 3 66 10 4 3a CBr4·2AlBr3 48 16 3:1:0.06 3 58 8 3 4 CBr4·2AlBr3 15 10 1.5:1:0.2 1 20 7 1 5 CBr4·2AlBr3 45 20 2.2:1:0.05 1 37 4 1 6 CBr4·2AlBr3 45 20 2.2:1:0.05 2 86 6 traces 7 CBr4·2AlBr3 48 16 3:1:0.05 3 47 6 2 8 CBr4·3AlBr3 45 20 2.2:1:0.05 2 82 12 2 9 CBr4·AlBr3 45 20 2.2:1:0.1 2 17 22 2 10 CCl4·3AlBr3 45 20 2.2:1:0.04 2 61 8 2 11 CCl4·3AlBr3 42 18 2.3:1:0.06 2 46 18 7 12 CHCl3·3AlBr3 42 18 2.3:1:0.06 1 50 traces traces 13 CH2Br2·2AlBr3 45 20 2.2:1:0.05 2 traces 0 0 CBr4 CBr3 Al2Br7 2AlBr3 C2H6 + CBr3 Al2Br7 C2H5 Al2Br7 + CHBr3 CO EtCO 1 ROH Scheme 2Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) References 1 H.Bahrmann, in New Syntheses with Carbon Monoxide, ed. J. Falbe, Springer, Berlin, 1980, ch. 5. 2 G. A. Olah, O. Farooq and G. K. S. Prakash, in Activation and Functionalization of Alkanes, ed. C. L. Hill, Wiley–Interscience, New York, 1989, ch. 2. 3 J. Sommer and J.Bukala, Account Chem. Res., 1993, 26, 370. 4 H. Hogeveen, in Advances in Organic Chemistry, ed. V. Gold, Academic Press, London, 1973, vol. 10, p. 29. 5 Q. Xu and Y. Souma, Topics in Catalysis, 1998, 6, 17. 6 I. Akhrem, Topics in Catalysis, 1998, 6, 27. 7 R. Paatz and G. Weisgerber, Chem. Ber., 1967, 100, 984. 8 I. S. Akhrem, A. V. Orlinkov, L. V. Afanas’eva and M. E. Vol’pin, Izv. Akad. Nauk, Ser. Khim., 1996, 1214 (Russ. Chem. Bull., 1996, 45, 1154). 9 I. Akhrem, A. Orlinkov, L. Afanas’eva, P. Petrovskii and S. Vitt, Tetrahedron Lett., 1999, 40, 5897. 10 I. S. Akhrem, S. Z. Bernadyuk and M. E. Vol’pin, Mendeleev Commun., 1993, 188. 11 M. Koch and W.Haaf, Org. Synth., 1964, 40, 1. 12 Y. Fujiwa, K. Takaki and Y. Taniguchi, Synlett., 1996, 7, 591. Received: 17th May 1999; Com. 99/1489

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Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) Regiospecific cleavage of a triazole or pyrimidine ring in nitrotriazolo[1,5-a]pyrimidones Victor V. Voronin, Eugeny N. Ulomsky, Vladimir L. Rusinov* and Oleg N. Chupakhin Urals State Technical University, 620002 Ekaterinburg, Russian Federation. Fax: +7 3432 74 0458; e-mail:rusinov@htf.ustu.ru The reaction of nitrotriazolo[1,5-a]pyrimidines 1 with primary amines leads to cleavage of the pyrimidine ring, whereas triazole ring opening takes place in the reaction of 1 with secondary amines.One of the reasons of our continuous interest in condensed azoloazine derivatives bearing a bridgehead nitrogen is their potential biological activity due to the structural similarity to purines. Indeed, a number of compounds possessing antitumor and antiviral activities1 have been found in this series.Recently, we became interested in nitrotriazolo[5,1-a]pyrimidones 1 because of their structural similarity to guanine and of the high antiviral activity of antimetabolites of guanosine and its precursors.2 A characteristic chemical property of azaindolizines is an enhanced tendency to ring cleavage by the action of nucleophiles and bases.Depending on the nature of reagents and on the reaction conditions, either azole or azine ring opening reaction can take place. However, the classification of the ring opening reactions of azaindolizines suggested recently on the basis of the molecular design approach3,4 cannot explain different reaction pathways for aza heterocycles with similar reagents.At the same time, these data are important for the comprehension of the reactivity of azoindolizines and the nature of their metabolism. In case of triazolo[1,5-a]pyrimidones,3,5 degradation of the pyrimidine ring by the action of nucleophiles appears to be a typical reaction; however, a single example of the triazole ring opening has been reported.6 Thus, the interaction of 3-b-D-ribofuranosyl- 5-chloro-1,2,4-triazolo[1,5-a]pyrimidin-7-one with liquid ammonia was found to yield 4-amino-2-N-cyano-b-Dribofuranosylaminopyrimidin- 6-one.It was found that the presence of an alkyl substituent in a triazole prevents azole ring opening in triazolo[1,5-a]pyrimidinone.6 We have found that nitrotriazolo[1,5-a]pyrimidine 1a reacts easily with pyrrolidine or morpholine to yield hetarylguanidines 2 and 3† (Scheme 1) after refluxing, instead of the expected cyanamide.An increase in the reaction time leads to the further transformation product, viz., 6-methyl-5-nitro-2-ethylaminopyrimidin- 4-one 4. In contrast to the literature data,6 we have found that 2-methylpyrimidin-7-one 1b is transformed only into the same compound 4‡ on refluxing in an excess of pyrrolidine.Opening of the pyrimidine ring via cleavage of the C7–N bond in triazolopyrimidones 1a,b was found to take place in the reaction with ammonia to form two products, viz., 3-R2-5-amino- 4-ethyl-1,2,4-triazole 5a,b and 3-amino-2-nitrocrotonamide 6.§ The use of a primary allylamine leads to the allylamide of 3-allylamino-2-nitrocrotonic acid 7¶ in addition to corresponding aminotriazoles 5a,b.The structure of triazole 5a is in good agreement with the literature data.7 Changes in the temperature conditions changed the reaction time rather than the reaction pathway. The times of full conversion of compound 1a by the action of corresponding amines are summarised in Table 1. † The general synthesis of 1-ethyl-1-(4-methyl-5-nitropyrimidin-6-on-2- yl)-3-tetramethylene guanidine 2 and 1-ethyl-1-(4-methyl-5-nitropyrimidin- 6-on-2-yl)-3-(3-oxapentamethylene) guanidine 3. 500 mg (2.24 mmol) of compound 1a was refluxed in 3 ml of pyrrolidine (10 min) or morpholine (20 min). The mixture was evaporated and treated with 50% isopropanol. The precipitate was filtered off. 2: yield 55%, mp 270 °C. 1H NMR (250 MHz, [2H6]DMSO) d: 1.17 (t, 3H), 1.80–2.00 (m, 4H), 2.08 (s, 3H), 3.30–3.50 (m, 4H), 3.78 (q, 2H), 8.78 (br.s, 2H). IR, n/cm–1: 1330, 1530 (NO2), 1680 (C=O), 1580 (C=NH); MS, m/z (%): 294 (3.15). 3: yield 73%, mp 180 °C. 1H NMR (250 MHz, [2H6]DMSO) d: 1.09 (t, 3H), 2.22 (s, 3H), 3.30–3.40 (m, 4H), 3.60–3.70 (m, 4H), 3.80 (q, 2H), 8.41 (br. s, 1H), 9.81 (br. s, 1H). IR, n/cm–1: 1310, 1530 (NO2), 1670 (C=O), 1580 (C=NH).‡ The synthesis of 2-ethyl-4-methyl-5-nitropyrimidin-6-one 4. 500 mg (2.11 mmol) of compound 1b was refluxed in 3 ml of pyrrolidine for 40 min. Pyrrolidine was evaporated. The residue was recrystallised from 20% acetic acid. Yield 83%, mp 285 °C. 1H NMR (250 MHz, [2H6]DMSO) d: 1.18 (t, 3H), 2.28 (s, 3H), 3.20–3.50 (m, 2H), 7.33 (br.s, 1H), 11.43 (br. s, 1H). IR, n/cm–1: 1510, 1320 (NO2), 1680 (C=O), 3280, 1250 (NH). § The synthesis of 3-amino-2-nitrocrotonamide 6. 500 mg (2.24 mmol) of compound 1a was added to 5 ml of a methanolic ammonia solution. The mixture was kept at room temperature for a week. The solvent was evaporated. The residue was recrystallised from water. Yield 77%, mp 202 °C. 1H NMR (250 MHz, [2H6]DMSO) d: 2.14 (s, 3H), 7.35 (br.s, 1H), 7.75 (br. s, 1H), 8.90 (br. s, 1H), 9.80 (br. s, 1H). IR, n/cm–1: 1510, 1370 (NO2), 1650 (C=O), 3300, 3150, 1270 (NH2). MS, m/z (%): 145 (48.34). ¶ General synthesis of 3-R-5-amino-4-ethyl-1,2,4-triazoles 5a,b and allylamide of 3-allylamino-2-nitrocrotonic acid 7. Compound 1 (2 mmol) was refluxed in 5 ml of allylamine for approximately 5–10 min.Allylamine was evaporated in vacuo. The residue was dissolved in 10 ml of hot chloroform. After cooling white crystals of triazole 5 were filtered off. The filtrate was evaporated. The residue was recrystallised from octane to give allylamide 7. 5a: yield 82%, mp 195 °C (lit.,7 mp 200–201 °C). 1H NMR (250 MHz, [2H6]DMSO) d: 1.23 (t, 3H), 3.74 (q, 2H), 5.66 (br. s, 2H), 7.89 (s, 1H). IR, n/cm–1: 3300, 3400 (NH2), 1380, 2920 (CH).MS, m/z (%): 112 (100.00). 5b: yield 79%, mp 247 °C. 1H NMR (250 MHz, [2H6]DMSO) d: 1.14 (t, 3H), 2.17 (s, 3H), 3.71 (q, 2H), 5.53 (br. s, 2H). IR, n/cm–1: 1120, 1680, 3300 (NH2), 1370, 2980 (CH). MS, m/z (%): 126 (100.00). 7: yield 62%, mp 65 °C. 1H NMR (250 MHz, [2H6]DMSO) d: 2.07 (s, 3H), 3.72–3.82 (m, 2H), 4.10–4.18 (m, 2H), 5.00–5.30 (m, 4H), 5.75– 6.05 (m, 2H), 8.56 (t, 1H), 10.79 (t, 1H).IR, n/cm–1: 1250, 3450 (NH), 1650 (C=O), 1350, 1550 (NO2). MS, m/z (%): 225 (46.32). N N N N R1 O NO2 Me Et 1 3 5 7 1a,b N NH2 N N R1 Et O NO2 Me NH NH R2 R2 R2NH2 5a,b 6,7 N X NH X HN N NO2 Me O N Et NH 2,3 HN N NO2 Me O HN Et D R1 = H R1 = Me 4 2 = pyrrolidine a R1 = H b R1 = Me 6 R2 = H 7 R2 = CH2–CH=CH2 Scheme 1 N X N X 3 = morpholineMendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) Thus, 6-nitrotriazolo[1,5-a]pyrimidines 1, which are heterocyclic systems prone to azole and azine ring opening reactions, exhibit an ambident character. The type of bicyclic system cleavage does not depend on the amine basicity but depends on the reagent structure.Thus, ammonia and primary amines open an azine ring, whereas cycloalkyl imines open an azole ring.A plausible explanation of the observed reactivity of triazolo- [1,5-a]pyrimidines 1 consists in lower steric hindrances of primary amines in the course of the attack on the pyrimidine carbonyl. This work was financially supported by the Federal Special Scientific and Technical Programme ‘Investigations and Elaborations of Priority Directions in the Civil Science and Technology Development,’ the section ‘Fundamental Problems of Modern Chemistry’.References 1 (a) Y. Wang, R. T. Wheelhouse, L. Zhao, D. Langnel and M. F. G. Stevens, J. Chem. Soc., Perkin Trans. 1, 1998, 1669; (b) T. L. Pilicheva, V. L. Rusinov, L. G. Egorova, O. N. Chupakhin, G. V. Vladiko, L. V. Korobchenko and E.I. Boreko, Khim.-Farm. Zh., 1990, 24, 41 (in Russian); (c) G. Fischer, Z. Chem., 1990, 30, 305; (d) S. M. Hussain, A. S. Ali and A. M. El-Reedy, Indian J. Chem., Sect. B, 1998, 27, 421; (e) J. J. Hlavka, P. Bitha and Y. Lin, US Patent 4546181, 1985 (Chem. Abstr., 1986, 104, 225051). 2 Fundamental virology, ed. B. Fields, Raven Press, New York, 1986. 3 D. A. Maiboroda and E. V. Babaev, Khim. Geterotsikl. Soedin., 1995, 1445 [Chem. Heterocycl. Compd. (Engl. Transl.), 1995, 1251]. 4 D. A. Maiboroda and E. V. Babaev, J. Org. Chem., 1997, 62, 7100. 5 O. N. Chupakhin, V. L. Rusinov, A. A. Tumashov and T. L. Pilicheva, Khim. Geterotsikl. Soedin., 1989, 278 [Chem. Heterocycl. Compd. (Engl. Transl.), 1989, 235]. 6 (a) G. R. Revankar, R. K. Robins and R. L. Tolman, J. Org. Chem., 1974, 39, 1256; (b) M. Hori, K. Tanaka, T. Kataoka, H. Shimizu and E. Imai, Tetrahedron Lett., 1985, 26, 1321. 7 Y. Makisumi and H. Kano, Chem. Pharm. Bull., 1963, 11, 67. Table 1 Times of full conversion of 1a. Amine t/min Products pKa Ammonium hydroxide 10 5a and 6 9.25 Allylamine 25 5a and 7 9.69 Pyrrolidine 30 2 11.27 Morpholine 60 3 8.33 Received: 3rd June 1999; Com. 99/1495

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年代:1999

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Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) The influence of the structure of ethyl aryl chloromethylphosphonates on the catalytic effect of direct and reverse micellar systems Lucia Ya. Zakharova,* Raissa A. Shagidullina, Farida G. Valeeva and Lyudmila A. Kudryavtseva A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre, Russian Academy of Sciences, 420088 Kazan, Russian Federation.Fax: +7 8432 75 2253; e-mail: vos@iopc.kcn.ru The reactivity of ethyl aryl chloromethylphosphonates in the basic hydrolysis reactions in direct micelles of cetyltrimethylammonium bromide depends on both electronic and hydrophobic properties of the substituent in the aryl group, while in the sodium dodecyl sulfate–hexanol–water micellar system it depends only on the electronic nature.Organised media such as micelles, microemulsions and liquid crystals are considered as biomimetic systems acting via the host–guest mechanism.1 One of the most important features of biocatalysts is their substrate specificity, i.e., their high selectivity both in respect to the compounds of different functional classes and within homologous series.2 It is of interest to study the influence of the substrate structure on the catalytic effect of direct and reverse micelles in order to elucidate the catalytic mechanism of confined systems in polar and nonpolar media and to evaluate the contribution of noncovalent interactions to micellar catalysis. In this study, the kinetics of the basic hydrolysis of ethyl aryl chloromethylphosphonates 1–7 in direct micelles of cetyltrimethylammonium bromide (CTAB) and in the sodium dodecylsulfate (SDS)–hexanol–water reverse micellar system has been investigated (Scheme 1).Substrates 1–7 were prepared according to the previously reported procedure.3 The surfactants CTAB and SDS of ‘pure’ grade were twice recrystallised from ethanol. Micellar solutions were prepared by mixing ingredients in appropriate proportions and shaking vigorously until a transparent solution was obtained.4 The reaction was carried out under pseudo-first-order conditions and monitored by observing the absorption of leaving group anions using a Specord M-400 spectrophotometer equipped with temperature-controlled cell holders.The reaction in water with no surfactant added.In the series of substrates 1–3, a marked decrease in the reactivity occurs because of weakening the electron-seeking effect of the substituent X, resulting in destabilization of the leaving group. In the series of 3–7, a smoother decrease in the reactivity is observed because of an increase in the positive inductive effect with increasing alkyl chain length.5 The reaction in CTAB direct micelles. In the CTAB micellar solutions, the reaction rate increases by a factor of about 25 as compared with the reaction in water.This increase results from the electrostatic attraction of hydroxide ions to positively charged CTAB micelles (Figure 1). The observed rate constant (kobs) decreases with decreasing electronegativity of X in the series of 1–3.The tendency in the reactivity change in the series of substrates 3–7 is opposite to that in water, namely, the highest kobs value is observed for 6 (X = n-octyl), and the lowest one, for 3 and 4 (X = H and Et, respectively). The substituent effect on the reactivity in CTAB micelles decreases in the following order: NO2 > Br > n-octyl > i-dodecyl > n-hexyl > Bu ~ Et ~ H.The kinetic data were treated in terms of a pseudophase model using the equation:6 where k2,w and k2,m (dm3 mol–1 s–1) are the second-order rate constants in the aqueous and micellar phases, respectively; KS and KOH (dm3 mol–1) are the substrate and nucleophile binding constants, respectively; V is the molar volume of the surfactant, assumed to be equal to 0.3 dm3 mol–1; C is the CTAB concentration minus the critical micelle concentration (cmc).The approach developed by Berezin makes it possible to differentiate the factors responsible for the micellar rate effects expressed as (kobs /kw)max using the equation where kw is the pseudo-first-order rate constant of the reaction in water. The first term in the right side of equation (2) is associated with the influence of the micellar microenvironment (Fm) and the second term reflects concentrating the reagents in micelles (Fc).Table 1 demonstrates that the main reason for the acceleration of the reaction is an increase in local concentrations of the reagents in the CTAB micelles. The concentration factor (Fc) increases with alkyl chain length of X and varies in the range 150–640.This means that an acceleration by two orders of magnitude can be observed if the micellar microenvironment favours the reaction. However, a dramatic decrease in the reactivity with transferring the reaction from water to a micellar pseudophase (Fm < 1) results in the reduction of the micellar rate effect by a factor of 6–25. The reaction in the SDS reverse micellar system.In accordance with the pseudophase approach, there are three pseudophases O X P ClH2C EtO O + 2OH O X+ H2 O O P ClH2C EtO O 1–7 1 X = NO2 2 X = Br 3 X = H 4 X = Et 5 X = Bu 6 X = n-octyl 7 X = i-dodecyl Scheme 1 Table 1 Kinetic data (Figure 1) treated in terms of equation (1). Substrate k2,w/dm3 mol–1 s–1 (kobs /kw)max KS/dm3 mol–1 KOH/dm3 mol–1 k2,m/dm3 mol–1 s–1 Fc Fm FcFm 1 4.0 7.5 1775 240 0.055 432 0.014 6 2 0.55 5.5 945 135 0.016 240 0.028 6.3 3 0.24 5 400 90 0.01 144 0.042 6 4 0.19 7 800 75 0.0098 146 0.053 7.7 5 0.16 9 1675 87 0.0082 190 0.051 9.8 6 0.12 22 2350 350 0.0043 604 0.037 22.5 7 0.08 24 1490 470 0.0031 640 0.039 24.9 kobs= , k2,w + k2,mKSKOHC/V (1 + KSC)(1 + KOHC) (1) (kobs /kw)max= , k2,m k2,w KSKOH V(KS 1/2 + K1/2 OH)2 (2)Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) in reverse micelles (water pool formed with incased water surrounded by a surfactant monolayer with polar head groups turned into the micellar interior and hydrophobic tails at the exterior in contact with oil).7 It is believed that the reaction of a hydrophobic substrate with a hydrophilic nucleophile occurs at the interface where the hydrophilic microenvironment favours the solubilization of both reagents. The kinetics of the reaction was measured at the molar ratios W = [H2O]/[SDS] and Z = = [hexanol]/[SDS] varied within the limits 9.8–37 and 5–22, respectively. The kinetic data are shown in Figures 2–4.Note that depending on the substrate structure and experimental conditions (surfactant, NaOH and water concentrations) either catalysis or inhibition of the reaction can be observed, as compared with the reaction in water.As can be seen in Figures 2 and 3, in the series of substrates 1–4 a marked reduction in the reactivity occurs. The highest acceleration factors for these substrates are 30, 14, 4 and 2, respectively. An increase in the alkyl-chain length in the series of 4–7 does not affect kobs.Thus, in the SDS-based reverse micellar system, a decrease in the electron-seeking effect of X results in a marked lowering of kobs, while an increase in the hydrophobicity exerts no effect. In general, the reactivity in the SDS reverse micellar system decreases in the following order: NO2 > Br > H > Et ~ ~ Bu ~ n-octyl ~ i-dodecyl. The observed rate constants decrease with surfactant concentration and, for 1–3, with water content.An analogous tendency was observed in earlier studies for the reactions occurring at the interface.8,9 It is of interest that, in the case of substrates 4–7, kobs was found to be independent of W (Figure 4). The kinetic data were treated in terms of the pseudophase model by analogy with ref. 9. For a reaction occurring at the interface, in the case when one of the reactants is distributed between an aqueous pseudophase and a surface layer, and the other reactant is distributed between an oil pseudophase and the surface layer, kobs is expressed as follows:8 where ki can be expressed in terms of the pseudo-first-order rate constant k'i and the molar ratio between the nucleophile at the interface and the [SDS], k'i = ki[OH]/[SDS]; PS and POH are the partition coefficients of the substrate and the nucleophile.The model was detailed earlier.10 Table 2 demonstrates that the partition constants PS of the substrates are almost unaffected by the substrate hydrophobicity. Note that, for substrates 2 and 3, k2,i /k2,w > 1, i.e., the micellar microenvironment exerts a favourable influence on the reaction rate, while for substrates 4–7, the above ratio is less than 1, thus indicating an unfavourable effect on the reactivity of the reaction transfer from water to the interface.Apparently, in this reaction series, high sensitivity to the microenvironment of reagents is observed so that even a slight change in the local polarity or orientation can result in the transition from catalysis to inhibition.Thus, we found that in the direct micelles of CTAB catalysis of the test reaction was observed. The main factor contributing to the micellar rate effect is concentrating reagents in micelles, while the micellar microenvironment exerts a negative effect 3.0 2.5 2.0 1.5 1.0 0.5 0.0 30 25 20 15 10 5 0 0.000 0.005 0.010 0.015 CCTAB/mol dm–3 kobs/10–3 s–1 kobs/10–3 s–1 1 2 3 4 5 6 7 Figure 1 The observed rate constants of basic hydrolysis of 1–7 in CTAB micellar solutions as functions of the surfactant concentration (0.001 M NaOH, 25 °C).The curve numbers correspond to those of the substrates in Scheme 1. 0.25 0.20 0.15 0.10 0.05 0.00 0.1 0.2 0.3 0.4 0.5 0.6 0.7 kobs /s–1 CSDS/mol dm–3 0.12 0.10 0.08 0.06 0.04 0.02 0.00 15 20 25 30 35 40 kobs/s–1 W Figure 2 The observed rate constants of basic hydrolysis of 1 in the SDS reverse micellar system as function of the surfactant concentration (W = 22.8, 0.002 M NaOH, 25 °C).Insert: the dependence of the observed rate constant of basic hydrolysis of 1 in the SDS reverse micellar system on the water content. 0.010 0.008 0.006 0.004 0.002 0.0 0.2 0.4 0.6 0.8 0.05 0.04 0.03 0.02 0.06 kobs /s–1 CSDS/mol dm–3 kobs /s–1 Figure 3 The observed rate constants of basic hydrolysis of 2–7 in the SDS reverse micellar system as functions of the surfactant concentration (W = 15.1, 0.01 M NaOH, 25 °C).X =H X = Et X = Bu X = n-octyl X = i-dodecyl X = Br kobs= , kiPSPOH[OH]t (PS + Z)(POH + W)[SDS] (3) aKinetics of the basic hydrolysis of 1 in 0.002 M NaOH is inconsistent with equation (3) (see ref. 11). bIn order to calculate k2,i, the micellar molar volume V was assumed to be equal to 0.37 dm3 mol–1.8 Table 2 Kinetic data (Figure 3) treated in terms of the pseudophase model.a Substrate PS POH ki/s–1 kb 2,i / dm3 mol–1 k2,w/dm3 mol–1 k2,i /k2,w 2 100 7 5.40 2.00 0.55 3.6 3 80 2.2 1.90 0.70 0.24 2.9 4 80 40 0.15 0.05 0.20 0.26 5 70 9.4 0.3 0.11 0.16 0.69 6 90 90 0.14 0.05 0.12 0.42 7 60 40 0.14 0.05 0.08 0.62Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) on the reactivity. In the CTAB micelles, a principle of the recognition of substrates depending on their hydrophobicity is valid, i.e., a differentiating effect on the reactivity is observed. The electronic properties of substituents exert no influence on the micellar rate effect expressed as (kobs /kw)max.In the SDS reverse micellar system, both catalysis and inhibition of the reaction were observed depending on the substrate structure and experimental conditions. The micellar microenvironment mainly contributes to the micellar rate effect, while the concentration factor plays a minor role.In the reverse system, leveling in the reactivity of substrates of different hydrophobicity, as compared to water, was observed. This work was supported by the Russian Foundation for Basic Research (grant nos. 97-03-32372 and 99-03-32037a). References 1 J. H. Fendler, Chem. Rev., 1987, 87, 877. 2 A. L. Lehninger, Biochemistry, Worth Publishers, New York, 1972. 3 D. F. Toy and K. H. Rattenbury, US Patent 2922810, 1960, (Chem. Abstr., 1960, 54, 9848). 4 E. Rodenas and E. Perez-Benito, J. Phys. Chem., 1991, 95, 4552. 5 N. A. Loshadkin, in Toksichnye efiry kislot fosfora (Toxic Esters of Phosphorus Acids), ed. P. O’Brain, Mir, Moscow, 1964, p. 460 (in Russian). 6 K. Martinek, A. K. Yatsimirsky, A. V. Levashov and I. V. Beresin, Micellization, Solubilization and Microemulsions, ed. K. L. Mittal, Plenum Press, New York–London, 1977, 489. 7 Microemulsions: Structure and Dynamics, eds. S. E. Friberg and P. Bothorel, CRC Press, Boca Raton, 1988. 8 L. Garsia-Rio, J. R. Leis, M. E. Pena and E. Iglesias, J. Phys. Chem., 1993, 97, 3437. 9 L. Ya. Zakharova, F. G. Valeeva, L. A. Kudryavtseva, N. L. Zakhartchenko and Y. F. Zuev, Mendeleev Commun., 1998, 224. 10 P. Stilbs, J. Colloid Interface Sci., 1982, 87, 385. 11 L. Ya. Zakharova, F. G. Valeeva, L. A. Kudryavtseva and E. P. Zhil’tsova, Mendeleev Commun., 1999, 125. X =H X = Et X = Bu X = n-octyl X = i-dodecyl X = Br 0.008 0.006 0.004 0.002 8 12 16 20 24 W kobs/s–1 0.04 0.03 0.02 0.05 kobs /s–1 Figure 4 The observed rate constants of basic hydrolysis of 2–7 in the SDS reverse micellar system as functions of the water content (0.01 M NaOH, 25 °C). Received: 16th June 1999; Com. 99/1503

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年代:1999

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Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) Steric factor in reactions of substituted 2-trifluoromethylchromones with ammonia and primary amines Vyacheslav Ya. Sosnovskikh,* Valentin A. Kutsenko and Danil S. Yachevskii Department of Chemistry, A. M. Gor’ky Urals State University, 620083 Ekaterinburg, Russian Federation. Fax: +7 3432 61 5978; e-mail: Vyacheslav.Sosnovskikh@usu.ru Substituted 2-trifluoromethylchromones react with ammonia and primary amines at the activated double bond to form 3-aminoand 3-alkylamino-4,4,4-trifluoro-1-(2-hydroxyaryl)but-2-en-1-ones or 2-amino- and 2-alkylamino-2-trifluoromethylchroman-4-ones depending on the substituent in the 5-position of the chromone system.Previously,1–3 it was found that condensation of substituted 2-hydroxyacetophenones with trifluoroacetonitrile results in either hydroxy oxo enamines 1a,b or, in the presence of a substituent in the 6-position of the benzene ring, mixtures of hydroxy oxo enamines 1c,d and 2-amino-2-trifluoromethylchromanones 2c,d.Subsequently, compounds 1c,d were found (unpublished data) to undergo irreversible transformation in alcoholic solutions in the presence of ethylenediamine at room temperature with the formation of cyclic species 2c,d.The latter are stable substances and do not exhibit ring–chain tautomerization in solvents such as CDCl3 and [2H6]DMSO at room temperature (1H NMR data). Thus, with a CF3 group at the C(2) atom and R1 � H, the chromanone structure of 2 is energetically more favourable than aminoenone species 1. Hydrolysis of compounds 1a–d under mild conditions1 gives 2-hydroxy-2-trifluoromethylchroman-4-ones 3a–d, which can also be prepared on condensation of corresponding methyl ketones with ethyl trifluoroacetate,4 and boiling of chromanones 2c,d and 3a–d in ethanol with catalytic amounts of HCl results in 2-trifluoromethylchromones 4a–d.4 The aim of this study was to examine the reactions of substituted 2-trifluoromethylchromones 4a–d with ammonia and primary amines. It is well known5–7 that 2-methylchromones undergo ring opening under the action of amines to form corresponding aminoenones with a 2-hydroxyaryl substituent at the carbonyl group.In this connection, taking into account published data,1–3 it is believed that 2-trifluoromethylchromones 4a–d will either exhibit a similar behaviour or, because of high electron-withdrawing capability of the CF3 group (at R1 � H), give products of amine addition to the double bond without opening the pyrone ring.We found that the structure of products strictly depends on the substituent in the 5-position of the chromone system: at R1 � H, reactions of chromones 4 with ammonia and primary amines are arrested at the step of nucleophilic addition and at R1 = H proceed further and are accompanied by opening of the pyrone ring to form corresponding aminoenones.Thus, the reactions of ammonia, methylamine (25% aqueous solutions) and benzylamine with alcoholic solutions of chromones 4a,b proceed at room temperature in 1–3 h and result in yellow hydroxy oxo enamines 1a,b, 5a,b and 6a,b, respectively,† in 58–88% yields.At the same time, chromones 4c,d having substituents in the 5-position (R1 � H) react with the above amines under the same conditions to form chromanones 2c,d, 7c,d and 8c,d (25–76% yields)‡ in 0.5 h (NH3 and MeNH2) or 7 h (PhCH2NH2). To explain the structural difference between the products, it is reasonable to suggest that, regardless of the position of a substituent in the aromatic ring, the reaction proceeds via pyrone ring opening to form intermediate B being in the equilibrium with cyclic intermediate A, the primary product of nucleophilic addition.At R1 � H, intermediate B is destabilised because of steric hindrances that occur between the substituent R1 and vinyl hydrogen of the enamine unit and hinder the formation of a planar conformation. Interactions that are inevitable in the structure of B at R1 � H render the open species energetically less favourable and shift the equilibrium towards intermediate A.The latter intermediate leads to chromanones 2c,d, 7c,d and 8c,d, which are incapable of ring–chain tautomerization. At R1 = H, the equilibrium is shifted towards intermediate B, which forms aminoenones 1a,b, 5a,b and 6a,b upon proton transfer.These aminoenones exhibit planar conformations stabilised by two intramolecular hydrogen bonds and, because of this, are not prone to cyclization.§ Taking into account that aminoenones 1c,d easily convert to chromanones 2c,d, the possibility of intermediate B converting into aminoenones with R1 � H, which undergo irreversible cyclization to chromanones R2 R3 R4 OH R1 O CF3 NH2 R1 R2 R3 R4 O O NH2 CF3 R1 � H R1 R2 R3 R4 O O OH CF3 1a–d 2c,d 3a–d THF HCl R1 R2 R3 R4 O O 4a–d D HCl CF3 HCl D a R1 = R2 = R3 = R4 = H b R1 = R2 = H, R3 + R4 = benzo c R1 = R3 = Me, R2 = R4 = H d R1 + R2 = benzo, R3 = R4 = H R1 R2 R3 R4 O H O H CF3 N H R R1 R2 R3 R4 O O NHR CF3 4a–d 1a,b, 5a,b, 6a,b 2c,d, 7c,d, 8c,d RNH2 R1 = H R1 � H a R1 = R2 = R3 = R4 = H b R1 = R2 = H, R3 + R4 = benzo c R1 = R3 = Me, R2 = R4 = H d R1 + R2 = benzo, R3 = R4 = H 1,2 R = H 5,7 R = Me 6,8 R = CH2PhMendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) 2c,d, 7c,d and 8c,d under the reaction conditions, cannot also be excluded. The appearance of a doublet of quartets of the N–Me group is the characteristic feature of the 1H NMR spectra of aminoenones 5a and 5b, which have the Z-configuration of the double † Compounds 1a,b were described in refs. 1 and 2. 4,4,4-Trifluoro-1-(2-hydroxyphenyl)-3-methylaminobut-2-en-1-one 5a: yield 78%, mp 118–119 °C. 1H NMR (100 MHz, CDCl3) d: 3.15 (dq, 3H, MeN, J 5.8, 1.4 Hz), 6.22 (s, 1H, =CH), 6.85 [td, 1H, H(5), J 8.0, 1.4 Hz], 6.95 [dd, 1H, H(3)], 7.40 [td, 1H, H(4)], 7.66 [dd, 1H, H(6)], 10.4 (br.s, 1H, NH), 12.69 (s, 1H, OH). IR (Vaseline oil, n/cm–1): 3190 (br., NH), 1625 (C=O), 1580, 1570 (C=C, NH). Found (%): C, 53.87; H, 4.22; N, 5.76. Calc. for C11H10F3NO2 (%): C, 53.88; H, 4.11; N, 5.71. 4,4,4-Trifluoro-1-(1-hydroxynaphth-2-yl)-3-methylaminobut-2-en-1-one 5b: yield 88%, mp 138–139 °C. 1H NMR (100 MHz, CDCl3) d: 3.13 (dq, 3H, MeN, J 5.8, 1.3 Hz), 6.27 (s, 1H, =CH), 7.15–7.78 (m, 5H, Harom), 8.36–8.48 (m, 1H, peri-H), 10.3 (br.s, 1H, NH), 14.37 (s, 1H, OH). IR (Vaseline oil, n/cm–1): 3180 (br., NH), 1620 (C=O), 1600, 1575, 1500 (C=C, NH). Found (%): C, 61.13; H, 4.24; N, 4.82. Calc. for C15H12F3NO2 (%): C, 61.02; H, 4.10; N, 4.74. 3-Benzylamino-4,4,4-trifluoro-1-(2-hydroxyphenyl)but-2-en-1-one 6a: yield 58%, mp 98–99 °C. 1H NMR (100 MHz, CDCl3) d: 4.60 (d, 2H, CH2, J 6.3 Hz), 6.28 (s, 1H, =CH), 6.75–6.96 [m, 2H, H(5), H(3)], 7.30– 7.47 [m, 6H, H(4), Ph], 7.66 [dd, 1H, H(6), J 8.0, 1.4 Hz], 10.6 (br. s, 1H, NH), 12.61 (s, 1H, OH). IR (Vaseline oil, n/cm–1): 3190 (br., NH), 3080, 3050 (=CH arom.), 1630 (C=O), 1580, 1530 (C=C, NH). Found (%): C, 63.47; H, 4.52; N, 4.36.Calc. for C17H14F3NO2 (%): C, 63.55; H, 4.39; N, 4.36. 3-Benzylamino-4,4,4-trifluoro-1-(1-hydroxynaphth-2-yl)but-2-en-1-one 6b: yield 65%, mp 84–85 °C. 1H NMR (100 MHz, CDCl3) d: 4.63 (d, 2H, CH2, J 6.5 Hz), 6.34 (s, 1H, =CH), 7.17–7.86 (m, 10H, Harom), 8.36–8.48 (m, 1H, peri-H), 10.6 (br. s, 1H, NH), 14.31 (s, 1H, OH). IR (Vaseline oil, n/cm–1): 3180 (br., NH), 1620 (C=O), 1575, 1500 (C=C, NH).Found (%): C, 67.74; H, 4.57; N, 3.80. Calc. for C21H16F3NO2 (%): C, 67.92; H, 4.34; N, 3.77. ‡ Compounds 2c,d were described in refs. 2 and 3. 2-Trifluoromethyl-2-methylamino-5,7-dimethylchroman-4-one 7c: yield 60%, mp 119–120 °C. 1H NMR (100 MHz, CDCl3) d: 2.1 (br. s, 1H, NH), 2.32 (s, 3H, Me), 2.43 (s, 3H, MeN), 2.59 (s, 3H, Me), 2.95 (AB system, Dd 0.34 ppm, 2H, CH2, J 16.4 Hz), 6.69 (s, 1H, Harom), 6.75 (s, 1H, Harom).IR (Vaseline oil, n/cm–1): 3350 (br., NH), 1680 (C=O), 1620, 1570, 1520 (NH, arom.). Found (%): C, 57.25; H, 5.32; N, 4.99. Calc. for , 57.14; H, 5.16; N, 5.13. 2-Trifluoromethyl-2-methylaminobenzo[f]chroman-4-one 7d: yield 76%, mp 103–104 °C. 1H NMR (100 MHz, CDCl3) d: 2.3 (br. s, 1H, NH), 2.45 (s, 3H, MeN), 3.13 (AB system, Dd 0.36 ppm, 2H, CH2, J 16.4 Hz), 7.14–8.06 (m, 5H, Harom), 9.38 (d, 1H, peri-H).IR (Vaseline oil, n/cm–1): 3400 (br., NH), 1660 (C=O), 1625, 1600, 1575, 1515 (NH, arom.). Found (%): C, 60.90; H, 3.98; N, 4.61. Calc. for C15H12F3NO2 (%): C, 61.02; H, 4.10; N, 4.74. 2-Benzylamino-2-trifluoromethyl-5,7-dimethylchroman-4-one 8c: yield 57%, mp 93–94 °C. 1H NMR (100 MHz, CDCl3) d: 2.3 (br. s, 1H, NH), 2.32 (s, 3H, Me), 2.59 (s, 3H, Me), 2.97 (AB system, Dd 0.36 ppm, 2H, CH2, J 16.4 Hz), 3.92 (m, 2H, CH2Ph), 6.72 (s, 2H, Harom), 7.0–7.3 (m, 5H, Ph). IR (Vaseline oil, n/cm–1): 3330 (br., NH), 3080, 3040 (=CH arom.), 1680 (C=O), 1620, 1575, 1515, 1500 (NH, arom.). Found (%): C, 65.38; H, 5.04; N, 4.01. Calc. for C19H18F3NO2 (%): C, 65.32; H, 5.19; N, 4.01. 2-Benzylamino-2-trifluoromethylbenzo[f]chroman-4-one 8d: yield 25%, mp 122–123 °C. 1H NMR (100 MHz, CDCl3) d: 2.5 (br. s, 1H, NH), 3.17 (AB system, Dd 0.36 ppm, 2H, CH2, J 16.5 Hz), 3.96 (m, 2H, CH2Ph), 7.05–8.07 (m, 10H, Harom), 9.38 (d, 1H, peri-H). IR (Vaseline oil, n/cm–1): 3425 (br., NH), 1680 (C=O), 1620, 1600, 1575, 1515, 1500 (NH, arom.). Found (%): C, 67.81; H, 4.28; N, 3.71.Calc. for C21H16F3NO2 (%): C, 67.92; H, 4.34; N, 3.77. § Judging from the IR spectra in Vaseline oil, in which the absorption band due to the C=O group at 1660–1680 cm–1 is absent, aminoenones 1a,b, 5a,b and 6a,b with R1 = H occur only in the open form both in the solid state and in CDCl3 solutions (1H NMR spectroscopy data). We assume the possibility of their cyclization to corresponding amino chromanones; however, the conditions for this transformation, which can be considered as a new example of reversible ring–chain tautomerization, remain to be found.bond.2 This is due to the splitting at the NH proton (J 5.8 Hz), which participates in the formation of the intramolecular hydrogen bond, and the spin–spin interaction (J 1.3–1.4 Hz), which is typical of 1H and 19F nuclei and results from the spatial proximity of the methyl and trifluoromethyl groups.8 For chromanones 8c and 8d, in addition to the AB system of the CH2(3) group, we observed a multiplet due to the benzyl methylene group whose diastereotopic protons are split because of the spin–spin interaction with the NH proton.Thus, depending on the substituent in the 5-position of the chromone system, the interaction of 2-trifluoromethylchromones 4a–d with ammonia and primary amines results in either the products of addition at the C(2) atom or the pyrone ring opening to form an aminoenone system.This fact is of interest with respect to both a new approach to the preparation of 2- amino- and 2-alkylamino-2-trifluoromethylchromanones and the synthesis of fluorine-containing N-substituted hydroxy oxo enamines, which cannot be obtained by direct condensation of nitriles with ketones.1–3 This work was supported by the Russian Foundation for Basic Research (grant no. 96-03-33373). References 1 V. Ya. Sosnovskikh and I. S. Ovsyannikov, Zh. Org. Khim., 1993, 29, 89 (Russ. J. Org. Chem., 1993, 29, 74). 2 V. Ya. Sosnovskikh, Mendeleev Commun., 1996, 189. 3 V. Ya. Sosnovskikh, Izv. Akad. Nauk, Ser. Khim., 1998, 362 (Russ. Chem. Bull., 1998, 47, 354). 4 W. B. Whalley, J. Chem. Soc., 1951, 3235. 5 G. Wittig and H. Blumenthal, Ber., 1927, 60, 1085. 6 W. Baker and V. S. Butt, J. Chem. Soc., 1949, 2142. 7 A. E. A. Sammour, J. Org. Chem., 1958, 23, 1222. 8 H.Günther, NMR Spectroscopy, George Thieme Verlag, Stuttgart, 1973 (in German). R1 R2 R3 R4 O O H CF3 NH2R R1 R2 R3 R4 O O NH2R CF3 4a–d 1a–d, 5a–d, 6a–d 2c,d, 7c,d, 8c,d RNH2 R1 � H A B R1 � H Received: 14th October 1998; Com. 98/

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年代:1999

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Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) Interaction of 2-trichloromethylchromones with ethylenediamine. A simple synthesis of 2-(2-hydroxyaroylmethylene)imidazolidines Vyacheslav Ya. Sosnovskikh* and Valentin A. Kutsenko Department of Chemistry, A. M. Gor’ky Urals State University, 620083 Ekaterinburg, Russian Federation. Fax: +7 3432 61 5978; e-mail: Vyacheslav.Sosnovskikh@usu.ru Reactions of 2-trichloromethylchromones with ethylenediamine at room temperature give 2-(2-hydroxyaroylmethylene)imidazolidines in high yields.It is well known that 2-acetonylideneimidazolidine1 and its analogues substituted at the acetyl group2 can be prepared by the interaction of ethylenediamine with b-dialkylaminoethynyl ketones and b-amino-b-trichloromethylvinyl ketones, respectively. 2-Phenacylideneimidazolidines were obtained by a reaction that involves desulfurization of phenacylthioimidazolines with triphenylphosphine as a thiophilic reagent.3 Here we report a synthesis of 2-phenacylideneimidazolidines by the interaction of 2-trichloromethylchromones 1a–f with ethylenediamine. Previously, chromone 1a was prepared by a reaction of 2-methylchromone with thionyl chloride in boiling benzene4 or by condensation of 2-hydroxyacetophenone with trichloroacetonitrile followed by treatment of the condensation product (3-amino-4,4,4-trichloro-1-phenylbut-2-en-1-one) with concentrated HCl.5 Using the latter method,5 we obtained 2-trichloromethylchromones 1a–f and found that the interaction of ethylenediamine with 1a–f is a simple and convenient method for synthesising 2-(2-hydroxyaroylmethylene)imidazolidines 2a–f.The reaction proceeded in ethanol or without solvent at room temperature in 3–5 h and afforded compounds 2a–f in 63–94% yields.† Most probably, the reaction begins with an attack of an ethylenediamine NH2 group on the C(2) atom of the chromone system resulting in pyrone ring opening and formation of an intermediate aminoenone with a 2-aminoethyl group at the nitrogen atom.Next, intramolecular replacement of the trichloromethyl group proceeds via addition–elimination steps, and 2-phenacyl-D2-imidazolines are formed. The last-mentioned compounds occur in the more stable ketoenamine form of 2-phenacylideneimidazolidines, which were the only species detected by 1H NMR spectroscopy.It was found previously that substituted chromone-2-carboxylic acid esters afforded 3-(2-hydroxyaroylmethylene)piperazin-2- ones6,7 by the reaction with ethylenediamine in ethanol. It is also well known that 2-methylchromones undergo ring opening under the action of ethylenediamine in an alcoholic solution at room temperature to form N,N'-ethylenebis[3-amino-1-(2- hydroxyaryl)but-2-en-1-ones],8 and 2-trifluoromethylchromones form 5-(2-hydroxyaryl)-7-trifluoromethyl-2,3-dihydro-1H-1,4- diazepines9 under the specified conditions.As for the properties of 2-trichloromethylchromones, the above reaction is the first example of a reaction of these compounds, except for the reaction of chromone 1a with an alcoholic alkali solution to form 4-hydroxycoumarin.4 According to X-ray diffraction analysis data,10 the structure of 2-pivaloylmethyleneimidazolidine, which was described previously,2 can be considered as the superposition of a ketoenamine tautomer and resonance charge-transfer structures.Because both of the hydrogen atoms are localised at nitrogen atoms, the iminoenol form was rejected. Taking into account these data and the possibility of forming an intramolecular hydrogen bond between hydroxyl and carbonyl groups, which stabilises the ketoenamine form relative to the iminoenol form, we believe that products 2a–f also exhibit the structure of ketoenamines with delocalised bonds.The electron-density delocalization is due to strong conjugation of lone electron pairs of nitrogen atoms with carbonyl oxygen, which is favoured by the second intramolecular hydrogen bond N–H···O responsible for flattening the ketoenamine fragment.Thus, 2-phenacylideneimidazolidines 2a–f can be considered as highly delocalised p-systems with a short strong hydrogen bond the nature of which has been studied intensively in recent years.11 The exchange of not only OH and NH protons, but also vinyl hydrogen atoms for deuterium occurred immediately after addition of CD3CO2D to solutions of compounds 2a–f in CDCl3.This is because of rapid H/D exchange due to an equilibrium between enol and keto forms of the phenacyl substituent of the symmetrically delocalised imidazolinium monocation, which is formed in an acidic medium. In this case, the AA'BB' multiplet of the ethylene unit becomes a singlet, as was the case in aliphatic analogues.2 R2 R1 R3 O O CCl3 1a–f (NH2CH2)2 R1 R2 R3 OH O CCl3 HN NH2 – CHCl3 R1 R2 R3 OH O N NH R1 R2 R3 O O N NH H H 2a–f R1 R2 R3 O O N NH H H d+ d+ 2d– a R1 = R2 = R3 = H b R1 = R3 = H, R2 = Me c R2 = R3 = H, R2 = OMe d R1 = R3 = H, R2 = Cl e R1 = OMe, R2 = R3 = H f R1 = R3 = Me, R2 = H Scheme 1 O But HN NH O But HN NH O But HN NH Scheme 2 R1 R2 R3 OD OD DN ND D R1 R2 R3 OD O DN ND D D 2a–f CD3CO2D Scheme 3Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) Enamino ketones 3a–e, acid hydrolysis of which gave chromones 1a–e, also react with ethylenediamine to form 2-phenacylideneimidazolidines 2a–e. However, in this case, the reaction proceeded at a lower rate (for 3–5 days); the yields of products were lower (25–40%); and analytically pure samples can be obtained only by chromatography.In spite of the fact that the product of 2-hydroxy-4,6-dimethylacetophenone condensation with CCl3CN occurs as cyclic species 3f,12 it also reacts with ethylenediamine to form imidazolidine 2f, suggesting that the CCl3 group at the hemiaminal carbon atom can be replaced. † 2-(2-Hydroxybenzoylmethylene)imidazolidine 2a.Chromone 1a (200 mg, 0.76 mmol) and ethylenediamine (200 ml, 180 mg, 3.0 mmol) were dissolved in 3 ml of ethanol. The reaction mixture was kept for 5 h at room temperature. The resulting crystals of imidazolidine 2a were washed with ethanol and recrystallised from C6H6 and ethanol, yield 110 mg (71%), mp 183–184 °C. 1H NMR (250 MHz, CDCl3) d: 3.74 (m, 4H, CH2CH2), 4.79 (br.s, 1H, NH), 5.38 (s, 1H, =CH), 6.74 [t, 1H, H(5), Jortho 7.2 Hz], 6.88 [d, 1H, H(3), Jortho 8.3 Hz], 7.26 [m, 1H, H(4)], 7.51 [d, 1H, H(6)], 9.19 (br. s, 1H, NH···O), 14.22 (br. s, 1H, OH); after addition of CD3CO2D: 3.96 (s, 4H, CH2CH2), 6.95 [m, 2H, H(3), H(5)], 7.48 [m, 1H, H(4)], 7.70 [m, 1H, H(6)]. IR (Vaseline oil, n/cm–1): 3360, 3200 (br., NH), 1615 (C=O), 1585, 1570, 1515.Found (%): C, 64.80; H, 6.12; N, 13.78. Calc. for C11H12N2O2 (%): C, 64.69; H, 5.92; N, 13.72. 2-(2-Hydroxy-5-methylbenzoylmethylene)imidazolidine 2b. Yield 89%, mp 195–196 °C. 1H NMR (250 MHz, CDCl3) d: 2.27 (s, 3H, Me), 3.63 (m, 2H, CH2), 3.79 (m, 2H, CH2), 4.75 (br. s, 1H, NH), 5.41 (s, 1H, =CH), 6.80 [d, 1H, H(3), Jortho 8.1 Hz], 7.09 [dd, 1H, H(4), Jmeta 2.0 Hz], 7.32 [d, 1H, H(6)], 9.20 (br.s, 1H, NH···O), 13.98 (br. s, 1H, OH); after addition of CD3CO2D: 2.27 (s, 3H, Me), 3.84 (s, 4H, CH2CH2), 6.84 [d, 1H, H(3), Jortho 8.4 Hz], 7.23 [m, 1H, H(4)], 7.42 [m, 1H, H(6)]. IR (Vaseline oil, n/cm–1): 3350, 3200 (br., NH), 1615 (C=O), 1570, 1515. Found (%): C, 66.02; H, 6.63; N, 12.70. Calc. for C12H14N2O2 (%): C, 66.04; H, 6.47; N, 12.84. 2-(2-Hydroxy-5-methoxybenzoylmethylene)imidazolidine 2c.Yield 84%, mp 165–166 °C. 1H NMR (250 MHz, CDCl3) d: 3.70 (m, 4H, CH2CH2), 3.75 (s, 3H, MeO), 4.87 (br. s, 1H, NH), 5.33 (s, 1H, =CH), 6.81 [d, 1H, H(3), Jortho 8.8 Hz], 6.90 [dd, 1H, H(4), Jmeta 3.1 Hz], 7.03 [d, 1H, H(6)], 9.17 (br. s, 1H, NH···O), 13.67 (br. s, 1H, OH); after addition of CD3CO2D: 3.74 (s, 3H, MeO), 3.83 (s, 4H, CH2CH2), 6.84 [d, 1H, H(3), Jortho 9.1 Hz], 7.01 [dd, 1H, H(4)], 7.07 [d, 1H, H(6), J 2.5 Hz].IR (Vaseline oil, n/cm–1): 3350, 3220 (br., NH), 1615 (C=O), 1570. Found (%): C, 61.48; H, 6.06; N, 12.07. Calc. for C12H14N2O3 (%): C, 61.53; H, 6.02; N, 11.96. 2-(2-Hydroxy-5-chlorobenzoylmethylene)imidazolidine 2d. Yield 94%, mp 238–239 °C. 1H NMR (250 MHz, CDCl3) d: 3.65 (m, 2H, CH2), 3.81 (m, 2H, CH2), 4.73 (br.s, 1H, NH), 5.31 (s, 1H, =CH), 6.82 [d, 1H, H(3), Jortho 8.7 Hz], 7.19 [dd, 1H, H(4), Jmeta 2.6 Hz], 7.46 [d, 1H, H(6)], 9.17 (br. s, 1H, NH···O), 14.17 (br. s, 1H, OH); after addition of CD3CO2D: 4.02 (s, 4H, CH2CH2), 6.96 [d, 1H, H(3), Jortho 8.9 Hz], 7.45 [dd, 1H, H(4), Jmeta 2.4 Hz], 7.73 [d, 1H, H(6)]; after addition of CF3CO2D: 4.11 (s, 4H, CH2CH2), 7.02 [d, 1H, H(3), Jortho 9.1 Hz], 7.55 [dd, 1H, H(4), Jmeta 2.3 Hz], 7.64 [d, 1H, H(6)].IR (Vaseline oil, n/cm–1): 3350, 3210 (br., NH), 1615 (C=O), 1570, 1515. Found (%): C, 55.31; H, 4.45; N, 11.82. Calc. for C11H11ClN2O2 (%): C, 55.36; H, 4.65; N, 11.74. 2-(2-Hydroxy-4-methoxybenzoylmethylene)imidazolidine 2e. Yield 83%, mp 192–193 °C. 1H NMR (250 MHz, CDCl3) d: 3.75 (m, 4H, CH2CH2), 3.79 (s, 3H, MeO), 4.64 (br. s, 1H, NH), 5.28 (s, 1H, =CH), 6.32 [d, 1H, H(5), Jortho 8.5 Hz], 6.38 [s, 1H, H(3)], 7.42 [d, 1H, H(6)], 9.05 (br. s, 1H, NH···O), 14.60 (br. s, 1H, OH); after addition of CD3CO2D: 3.83 (s, 3H, MeO), 3.99 (s, 4H, CH2CH2), 6.40 [d, 1H, H(3), Jmeta 2.0 Hz], 6.49 [dd, 1H, H(5), Jortho 8.7 Hz], 7.67 [d, 1H, H(6)].IR (Vaseline oil, n/cm–1): 3360, 3210 (br., NH), 1610 (C=O), 1550, 1520. Found (%): C, 61.26; H, 5.94; N, 11.82. Calc. for C12H14N2O3 (%): C, 61.53; H, 6.02; N, 11.96. 2-(2-Hydroxy-4,6-dimethylbenzoylmethylene)imidazolidine 2f. Yield 63%, mp 202–203 °C. 1H NMR (250 MHz, CDCl3) d: 2.23 [s, 3H, Me(4)], 2.42 [s, 3H, Me(6)], 3.59 (m, 2H, CH2), 3.74 (m, 2H, CH2), 4.80 (br. s, 1H, NH), 5.01 (s, 1H, =CH), 6.47 [d, 1H, H(5), Jmeta 0.7 Hz], 6.56 [d, 1H, H(3)], 9.41 (br.s, 1H, NH···O), 11.6–11.7 (br. s, 1H, OH); after addition of CD3CO2D: 2.23 [s, 3H, Me(4)], 2.35 [s, 3H, Me(6)], 3.76 (s, 4H, CH2CH2), 6.49 [s, 1H, H(5)], 6.60 [s, 1H, H(3)]. IR (Vaseline oil, n/cm–1): 3350 (NH), 1610 (C=O), 1570. Found (%): C, 67.25; H, 7.08; N, 11.91. Calc. for C13H16N2O2 (%): C, 67.22; H, 6.94; N, 12.06.The reduced reactivity of b-amino-b-trichloromethylvinyl ketones in comparison with 2-trichloromethylchromones can be explained by the fact that in aminoenones the CCl3 group is primarily replaced,13 and cyclization of ketene aminal intermediates is difficult because of the poor leaving capability of the NH2 group. Chromones 1a–f are free from this disadvantage, because first the phenol unit [O(1)–C(2) bond rupture] and then the trichloromethyl substituent‡ play the role of the leaving groups in these compounds.Thus, they can readily react not only with ethylenediamine, but also with trimethylenediamine. In the latter case, 2-phenacylidenehexahydropyrimidines are formed in good yields. Thus, unlike trichloromethylarenes14 and 2-trichloromethyl- 4-quinolones,15 which are synthetic equivalents of corresponding carboxylic acids, and also trichloromethyl ketones,16,17 which are selective acylating agents, 2-trichloromethylchromones behave as synthetic equivalents of inaccessible trichloropropynyl ketones in the reactions with aliphatic diamines and are of interest as new highly reactive synthons for preparing partially hydrogenated heterocycles.This work was supported by the Russian Foundation for Basic Research (grant no. 96-03-33373). References 1 I. G. Ostroumov, A. E. Tsil’ko, I. A. Maretina and A. A. Petrov, Zh. Org. Khim., 1988, 24, 1165 [J. Org. Chem. USSR (Engl. Transl.), 1988, 24, 1050]. 2 V. Ya. Sosnovskikh and M. Yu. Mel’nikov, Mendeleev Commun., 1998, 243. 3 M. D. Nair and J.A. Desai, Indian J. Chem., 1982, 21B, 4. 4 J. R. Merchant, A. R. Bhat and D. V. Rege, Tetrahedron Lett., 1972, 2061. 5 V. Ya. Sosnovskikh and I. S. Ovsyannikov, Zh. Org. Khim., 1993, 29, 89 (Russ. J. Org. Chem., 1993, 29, 74). ‡ According to our unpublished data, 2-trichloromethylchromones form corresponding 3-amino-4,4,4-trichloro-1-(2-hydroxyaryl)but-2-en-1-ones upon treatment with an alcoholic solution of ammonia at room temperature.These reactions demonstrate that pyrone ring opening primarily takes place in reactions of 2-trichloromethylchromones with N-nucleophiles, and next the intramolecular replacement of the CCl3 group occurs with the use of binucleophiles. a R1 = R2 = H b R1 = H, R2 = Me c R1 = H, R2 = OMe d R1 = H, R2 = Cl e R1 = OMe, R2 = H Scheme 4 R1 R2 OH O NH2 HN NH2 R1 R2 OH O CCl3 NH2 (NH2CH2)2 – CHCl3 3a–e 2a–e – NH3 O Me Me O NH2 CCl3 (NH2CH2)2 – CHCl3 3f 2fMendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) 6 V. A. Zagorevskii and D. A. Zykov, Zh. Obshch. Khim., 1960, 30, 3579 [J. Gen. Chem. USSR (Engl. Transl.), 1960, 30, 3547]. 7 V. I. Saloutin, I. T. Bazyl’, Z. E. Skryabina and O. N. Chupakhin, Izv. Akad. Nauk, Ser. Khim., 1994, 904 (Russ. Chem. Bull., 1994, 43, 849). 8 M. Owczarek and K. Kostka, Pol. J. Chem., 1991, 65, 345. 9 V. Ya. Sosnovskikh and V. A. Kutsenko, Izv. Akad. Nauk, Ser. Khim., 1999, 817 (in Russian). 10 V. Ya. Sosnovskikh, M. Yu. Mel’nikov and I. I. Vorontsov, unpublished data. 11 B. Schiøtt, B. B. Iversen, G. K. H. Madsen and T. C. Bruice, J. Am. Chem. Soc., 1998, 120, 12117. 12 V. Ya. Sosnovskikh, Izv. Akad. Nauk, Ser. Khim., 1998, 362 (Russ. Chem. Bull., 1998, 47, 354). 13 M. Coenen, J. Faust, S. Ringel and R. Mayer, J. Prakt. Chem./Chem.– Ztg., 1965, 27, 239. 14 L. I. Belen’kii, Khim. Geterotsikl. Soedin., 1993, 980 [Chem. Heterocycl. Compd. (Engl. Transl.), 1993, 29, 835]. 15 D. K. Wald and M. M. Joullié, J. Org. Chem., 1966, 31, 3369. 16 J. S. Roberto, F. Nome and M. C. Rezende, Synth. Commun., 1989, 19, 1181. 17 S. C. Hess, F. Nome, C. Zucco and M. C. Rezende, Synth. Commun., 1989, 19, 3037. Received: 4th February 1999; Com. 99/1438

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年代:1999

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Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) Heteroannelation of 3,4-dihydroisoquinoline with (3H,5H)-3-acylthiophene-2,4-diones: one-stage synthesis of new heterocyclic steroid analogues, 8-aza-16-thiagonanes Marina V. Budnikova,* Dmitry B. Rubinov, Lev G. Lis and Alexander L. Mikhal’chuk Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, 220141 Minsk, Belarus.Fax: + 7 017 263 7274; e-mail: rubinov@ns.iboch.ac.by New 8-aza-16-thiasteroid analogues, benzo[a]thieno[f]quinolizines, have been synthesised by the [2 + 4]heteroannelation of 3,4-dihydroisoquinoline with 3-acylthiotetronic acids. Condensed carbocycles and heterocycles are usually prepared by the following two ways: (1) a convergent synthesis which consists in the consecutive addition of rings to a principal carbocyclic or heterocyclic substrate and (2) a block synthesis when previously synthesised molecular units are combined at the final stage.1 The block strategy is more effective, and a large number of condensed nitrogen-containing heterocycles have been prepared in this manner, namely, benzo[a]- and dibenzo- [a,f]quinolizines,2(a) benzo[a]furo[f]quinolizines,2(b) benzo[a]- pyrrolo[f]quinolizines,2(c) benzo[a]pyrimidino[4,5-f]quinolizines2(d) and many others.3 All of the above compounds have been synthesised according to a single classical strategy involving the annelation ([2 + 4]cyclocondensation) reaction of cyclic Schiff’s bases, usually 3,4-dihydroisoquinolines, with b-dicarbonyl or b,b'-tricarbonyl compounds and their enol derivatives.2,3(b)–(d) To prepare new heterocycles, we tried to extend this approach by using 3,4-dihydroisoquinoline 1 and 3-acylthiotetronic acids such as (3H,5H)-3-acetylthiophene-2,4-dione 2a and (3H,5H)- 3-propionylthiophene-2,4-dione 2b in the annelation.4 We found that [2 + 4]cyclocondensation takes place when a mixture of compounds 1 and 2a or 2b is boiled in glacial acetic acid.† The reaction products are new heterocycles, benzo[a]thieno[f ]- quinolizines 3a,b.‡ Note that contrary to cyclocondensations with the participation of 2-acetylcyclohexane-1,3-diones2(a),5 and dihydrodehydracetic acid,3(a) which proceed in rather mild conditions, the reaction of 1 with 3-acylthiotetronic acids 2a,b, similarly to condensations with 2-acetylcyclopentane-1,3-dione6 and 3-acetyltetronic2(b) and 3-acetyltetramic2(c) acids, requires prolonged heating (8–15 h).We believe that this feature of b,b'-tricarbonyl compounds with five-membered rings is due to steric hindrances of the attack on a ring carbonyl by nitrogen atoms of Schiff’s bases. Prepared ABCD-tetracyclic 8-aza-16-thiagona-12,17-diones (benzo[a]thieno[4,3-f]quinolizines) 3a,b,5 as well as all their analogues which can be synthesised by this method, offer promise as biologically active substances and models for studying the structure–activity relationship in immune regulators such as † A mixture of 1.86 g (14.2 mmol) of 3,4-dihydroisoquinoline 1 and 2.24 g (14.2 mmol) of 3-acylthiotetronic acids 2a,b4 in 50 ml of glacial acetic acid was refluxed for 9 h and then allowed to cool to room temperature overnight.The precipitated orange crystals were separated, washed with acetic acid–diethyl ether (1:1), dried and recrystallised from a mixture of acetic and trifluoroacetic acids. Thus, 3.00 g (78.5%) of 8-aza-16-thiagona-1,3,5(10),13-tetraen-12,17-dione 3a (mp 320 °C, decomp.) and 3.01 g (75.6%) of 11-methyl-8-aza-16-thiagona-1,3,5(10),13- tetraen-12,17-dione 3b (mp 288–297 °C, decomp.) were obtained.condensed dibenzo[a,f]- and benzo[a]hetareno[f]quinolizine derivatives.7 Referenses 1 A. A. Akhrem and Yu. A. Titov, Total Steroid Synthesis, Plenum Press, New York, 1970. 2 (a) M. von Strandtmann, M. P. Cohen and J. Shavel, Jr., J. Org. Chem., 1966, 31, 797; (b) A. A. Akhrem, F. A.Lakhvich, L. G. Lis and V. N. Pshenichny, Zh. Org. Khim., 1979, 15, 1396 [J. Org. Chem. USSR (Engl. Transl.), 1979, 15, 1247]; (c) A. A. Akhrem, F. A. Lakhvich, V. N. Pshenichny, O. F. Lakhvich and B. B. Kuz’mitsky, Dokl. Akad. Nauk SSSR, 1978, 240, 595 (in Russian); (d) A. L. Mikhal’chuk, O. V. Gulyakevich, K. L. Krasnov, V. I. Slesarev and A. A. Akhrem, Zh. Org. Khim., 1993, 29, 1236 (Russ.J. Org. Chem., 1993, 29, 1026). 3 (a) A. A. Akhrem, A. M. Moiseenkov and V. A. Krivoruchko, Izv. Akad. Nauk SSSR, Ser. Khim., 1973, 1302 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1973, 22, 1258); (b) A. L. Mikhal’chuk, O. V. Gulyakevich, V. P. Peresada, A. M. Likhosherstov and A. A. Akhrem, Zh. Obshch. Khim., 1993, 63, 701 (Russ. J. Gen. Chem., 1993, 63, 494); (c) O. V.Gulyakevich and A. L. Mikhal’chuk, Dokl. Ross. Akad. Nauk, 1995, 345, 776 [Dokl. Chem. (Engl. Transl.), 1995, 345, 322]; (d) O. V. Gulyakevich and A. L. Mikhal’chuk, Dokl. Ross. Akad. Nauk, 1996, 350, 781 [Dokl. Chem. (Engl. Transl.), 1996, 350, 263]. 4 D. M. O’Mant, J. Chem. Soc. (C), 1968, 1501. 5 (a) A. L. Mikhal’chuk, O. V. Gulyakevich, A. A. Zenyuk, A. V. Korchik, L. G. Lis, V. A.Khripach, L. I. Ukhova and A. A. Akhrem, Dokl. Akad. Nauk SSSR, 1991, 317, 1397 [Dokl. Chem. (Engl. Transl.), 1991, 317, 106]; (b) O. V. Gulyakevich, A. L. Mikhal’chuk, A. I. Verenich, D. B. Rubinov, A. A. Zenyuk and A. A. Akhrem, Enaminy v organicheskom sinteze (Enamines in Organic Synthesis), Ur. Otd. RAN, Ekaterinburg, 1996, p.111 (in Russian); (c) A. L. Mikhal’chuk, O.V. Gulyakevich and A. A. Akhrem, Khim. Geterotsikl. Soedin., 1993, 86 [Chem. Heterocycl. Compd. (Engl. Transl.), 1993, 74]. ‡ For 3a: 1H NMR (200 MHz, CDCl3, TMS) d: 3.15 [t, 1H, C(11)HB, J 18.0 Hz], 3.22 [ttt, 1H, C(6)Ha, J 11.0, 13.0, 3.0 Hz], 3.29 [mmm, 1H, C(6)He, J 13.0, 3.0, 3.0 Hz], 3.45 [dd, 1H, C(11)HA, J 18.0, 5.0 Hz], 3.88 [ttt, 1H, C(7)Ha, J 13.0, 11.0, 3.0 Hz], 4.34 [mmm, 1H, C(7)He, J 13.0, 3.0, 3.0 Hz], 4.58 [d, 1H, C(15)HB, J 18.5 Hz], 4.68 [d, 1H, C(15)HA, J 18.5 Hz], 5.46 [dd, 1H, C(9)HX, J 18.0, 5.0 Hz], 7.20–7.48 [m, 4H, C(1)H, C(2)H, C(3)H, C(4)H]. 13C NMR (90 MHz, CF3CO2D, TMS) d: 30.056, 35.227, 40.850, 49.006, 60.724 (C-9), 109.985 (C-12), 127.263, 130.190, 130.866×2, 132.296, 134.287, 177.985 (C-14), 190.453, 200.015. IR (KBr, n/cm–1): 3100–2830, 1685 (sh.), 1672, 1608, 1580, 1565–1540, 1473–1445, 1396, 1347, 1320, 1285, 1230, 876, 830, 769.UV [EtOH, lmax/nm (e)]: 202.4 (36070), 230.0 (11595), 265.0 (13630), 302.4 (12245); lmin/nm (e): 219.1 (10235), 245.9 (6450), 280.0 (8985). Found (%): C, 66.24; H, 4.79; N, 5.07; S, 12.12. Calc. for C15H13NO2S (%): C, 66.40; H, 4.83; N, 5.16; S, 11.82. MS, m/z: 271.34. For 3b: 1H NMR (200 MHz, CDCl3, TMS) d: 0.78 [d, 3H, C(11)Me, J 7.0 Hz], 2.74 [m, 1H, C(11)He, J 4.0, 7.0 Hz], 2.99 [tt, 1H, C(6)He, J 4.0, 4.0, 12.0 Hz], 3.12 [ddd, 1H, C(6)Ha, J 4.0, 12.0, 12.0 Hz], 3.50 [ddd, 1H, C(7)Ha, J 4.0, 12.0, 12.0 Hz], 4.04 [d, 1H, C(15)HB, J 18.0 Hz], 4.16 [tt, 1H, C(7)He, J 4.0, 4.0, 12.0 Hz], 4.24 [d, 1H, C(15)HA, J 18.0 Hz], 5.10 [d, 1H, C(9)Ha, J 4.0 Hz], 7.15 [dd, 1H, C(1)H, J 2.0, 8.0 Hz], 7.21–7.42 [m, 3H, C(2)H, C(3)H, C(4)H].IR (KBr, n/cm–1): 3100–2830, 1698 (sh.), 1630, 1596, 1573, 1560 (sh.), 1500, 1477, 1460 (sh.), 1405, 1380, 1360–1330, 1307, 1292, 1240, 897, 811, 797, 770, 755. UV [EtOH, lmax/nm (e)]: 264.6 (15860), 303.9 (12950); lmin/nm (e): 238.1 (6290), 281.2 (7280). Found (%): C, 67.27; H, 5.14; N, 4.87; S, 11.50.Calc. for C16H15NO2S (%): C, 67.34; H, 5.30; N, 4.91; S, 11.24. MS, m/z: 285.36. N S R O O O 1 2a,b N S O O R H A B C D 3a,b AcOH D a R = H b R = Me 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17Mendeleev Communications Electronic Version, Issue 5, 1999 (pp. 171–212) 6 A. A. Akhrem, A. M. Moiseenkov, V. A. Krivoruchko, F. A. Lakhvich and A. I. Poselenov, Izv. Akad. Nauk SSSR, Ser. Khim., 1972, 2078 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1972, 21, 2014). 7 (a) N. A. Konoplya, O. V. Gulyakevich, A. L. Mikhal’chuk and B. B. Kuz’mitsky, Vesti Akad. Nauk Belarusi, Ser. Khim. Nauk, 1994, 91 (in Byelorussian); (b) A. A. Akhrem, B. B. Kuz’mitsky, F. A. Lakhvich, V. A. Khripach and Yu. L. Zhuravkov, Khymiya i biologiya immunoregulyatorov (Chemistry and Biology of Immunoregulators), Zinatne, Riga, 1985, p. 265 (in Russian). Received: 30th December 1998; Com. 98/1419

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