摘要:

Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) Synthesis of 2,5-cyclohexadien-4-one-spiro-3'-(2'-R-5',5'-dimethyl-1'-pyrrolines) by the Ritter reaction Vladimir A. Glushkov,*a Yurii V. Shklyaev,a Valentina I. Sokol,b Vladimir S. Sergienko*b and Victor V. Davidovc a Institute of Technical Chemistry, Ural Branch of the Russian Academy of Sciences, 614600 Perm, Russian Federation.Fax: +7 3422 12 4375; e-mail: cheminst@mpm.ru b N. S. Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, 117907 Moscow, Russian Federation. Fax:+7 095 954 1279; e-mail: sokol@ionchran.msk.ru c Peoples’ Friendship University of Russia, 117198 Moscow, Russian Federation. Fax:+7 095 433 1511; e-mail: vdavidov@mx.pfu.edu.ru Reactions of 1-(4'-methoxyphenyl)-2-methylpropene with nitriles RCN in concentrated sulfuric acid give 2,5-cyclohexadien-4-onespiro- 3'-(2'-R-5',5'-dimethyl-1'-pyrrolines) in good yields.In recent years, several methods to synthesise substituted 1-spiro- 2,5-cyclohexadien-4-ones have been described. These methods are based on an intramolecular electrophilic ipso-attack of para-substituted anisoles1,2 in the presence of Lewis acids.However, preparation of heterocyclic 1-spiro-2,5-cyclohexadienones has not yet been reported. In this work we present a simple synthesis of 2,5-cyclohexadien-4-one-spiro-3'-(2'-R- 5',5'-dimethyl-1'-pyrrolines) based on the Ritter reaction. Recently, we described the reaction of aromatic compounds activated by two methoxy groups with 1,1-dimethyloxirane and nitriles (tandem alkylation–cyclization procedure) leading to the substituted 3,3-dimethyl-6,7-(or 5,8-)dimethoxy-3,4-dihydroisoquinolines. 3 In the cyclisation stage, the carbimmonium ion is formed as an intermediate. Using anisole in the reaction with 1,1-dimethyloxirane and methyl thiocyanate, we expected to obtain substituted 7-methoxyisoquinoline, but to our surprise, only the corresponding 1-spiro-2,5-cyclohexadienone 2a was isolated in ~40% yield.Obviously, the para-methoxy group hinders ortho-attack that should lead to isoquinoline in the cyclisation stage. In fact, ipso-attack is favoured giving 2,5-cyclohexadiene-4-one-spiro-3'- (2'-R-5',5'-dimethyl-1'-pyrroline). In this work, we used 1-(4'-methoxyphenyl)-2-methylpropene as a carbocation source to avoid the first stage of the tandem reaction — alkylation by a tertiary oxirane — and to increase the yield.The yields of products 2a–c were 58–82%. Methyl isothiocyanate, benzonitrile or cyanoacetic ester were used as nitrile components.† The reaction proceeds according to Scheme 1. The corresponding 7-methoxyisoquinolines were formed only in trace amounts (TLC data).The structures of the compounds obtained 2a–c and 3‡ were confirmed by elemental analysis, IR and 1H NMR spectroscopy, and compound 2a was studied additionally by mass spectrometry and X-ray diffraction.§ The general view of molecule 2a is given in Figure 1. In the course of the reaction, semiketal 3 was isolated, which can be converted to 2b. Compounds 2b,c were isolated as semihydrates; in these compounds water molecules apparently bridge the carbonyl groups at two cyclohexadiene rings by forming hydrogen bonds.Thus, by changing the substituents in the aromatic ring, we changed the reaction of the carbimmonium ion, and an easy and † A typical experimental procedure is given below. A mixture of 1-(4'-methoxyphenyl)-2-methylpropene (16.2 g, 0.1 mol) and an appropriate nitrile (0.1 mol) in 100 ml of toluene was added dropwise to concentrated sulfuric acid (50 ml, 0.94 mol) during 30 min with vigorous stirring (the temperature was maintained in the range 20–50 °C; for 2a, in the range 20–25 °C).The reaction mixture was stirred for 1 h, poured into 300 ml of cold water, and stirred again. The resulting water layer was quickly separated.The organic layer was washed with 150 ml of water. In the case of 2a, the combined water layers were washed with 40 ml of toluene and then basified with ammonium carbonate to pH 8. Compound 2a was filtered off, dried in air and recrystallised first from 50% aqueous ethanol and then from a hexane–chloroform mixture. Compounds 2b,c precipitated as colourless crystals (2b) or a yellowish tar (2c) from the organic layer 3–15 min after washing it with water.Recrystallisation of 2b first from toluene and then from ethanol afforded compound 3. Refluxing semiketal 3 with 200 mg of p-toluenesulfonic acid in toluene (1 h), distilling off the solvent and recrystallising the precipitate from toluene gave 2b semihydrate. The tar of compound 2c was dissolved in CHCl3, washed with aqueous NaHCO3 and water, and dried with anhydrous magnesium sulfate; after removing the solvent, the substance was then recrystallised from acetone–water and hexane–CH2Cl2 mixtures.MeO Me Me C R N H+ MeO N Me Me R MeO N Me Me R H2O – H+ MeO N Me Me R HO – MeOH O N Me Me R EtO N Me Me Ph HO 1a–c 2a–c 3 a R = SMe b R = Ph c R = CH2COOEt Scheme 1 C(1) C(2) C(3) C(4) C(5) C(6) C(7) C(8) C(9) C(10) C(11) C(12) O(1) S(1) N(1) Figure 1 The structure of compound 2a.Selected bond lengths (Å): C(1)–N(1) 1.264(3), C(9)–N(1) 1.493(3), C(1)–S(1) 1.757(2), C(12)–S(1) 1.789(3), C(5)–O(1) 1.230(2). (The averaged values for two independent molecules.)Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) convenient synthesis of 2,5-cyclohexadiene-4-one-spiro-3'-(2'- R-5',5'-dimethyl-1'-pyrrolines) was thereby achieved.‡ 2a: yield 82%, mp 95–97 °C. 1H NMR (80 MHz, CDCl3) d: 1.38 (s, 6H, 5'-Me), 2.18 (s, 2H, 4'-CH2), 2.33 (s, 3H, SMe), 6.22 (d, 2H, 3-H and 5-H, J 10.2 Hz), 6.71 (d, 2H, 2-H and 6-H, J 10.0 Hz). IR (Nujol, n/cm–1): 1700 (weak), 1660 (s), 1625, 1585 (s), 1375, 1325, 1255, 1225, 1170, 1130, 1070 (s), 955 (s), 860 (s).MS, m/z: 221 [M+]. 2b: yield 58%, mp 145–146 °C (semihydrate). 1H NMR (80 MHz, CDCl3) d: 1.37 (s, 6H, 5'-Me), 2.98 (s, 2H, 4'-CH2), 5.72 (br. s, 1H, H2O), 6.65 (d, 2H, 3-H and 5-H), 6.92 (d, 2H, 2-H and 6-H), 7.25–7.60 (m, 5H, Harom). IR (Nujol, n/cm–1): 3400 (OH), 3200 (br., OH), 1630, 1610, 1590, 1540, 1315, 1255, 1230, 1175, 950. 2c: yield 64%, mp 100–103 °C (semihydrate). 1H NMR (80 MHz, CDCl3) d: 1.18 (t, 3H, Me), 1.26 (s, 6H, 5'-Me), 2.87 (s, 2H, a-CH2), 3.16 (s, 2H, 4'-H), 4.03 (q, 2H, OCH2), 6.54–6.68 (m, 3H, 3-H, 5-H and OH), 6.79 (d, 2H, 2-H and 6-H).IR (Nujol, n/cm–1): 3390 (OH), 3260 (br., OH), 1730 (O–C=O), 1640, 1615, 1590, 1545, 1510, 1280, 1270, 1255, 1230, 1175, 1155, 1175, 1155, 1100, 1045, 955. 3: yield 55%, mp 154–157 °C. 1H NMR (80 MHz, CDCl3) d: 1.13 (t, 3H, Me), 1.37 (s, 6H, 5'-Me), 2.98 (s, 2H, 4'-H), 3.46 (q, 2H, OCH2), 5.75 (s, 1H, OH), 6.65 (d, 2H, 3-H and 5-H), 6.90 (d, 2H, 2-H and 6-H), 7.25–7.50 (m, 5H, Harom). IR (Nujol, n/cm–1): 3410 (OH), 3200 (br., OH), 1635, 1610 (shoulder), 1535, 1260, 1230, 1180, 1135, 840. § Crystallographic data for 2a: C12H15NOS, monoclinic, space group P21/a, a = 13.404(3), b = 11.303(2), c = 17.086(3) Å, b = 105.47(3)°, V = 2494.8(8) Å3, Z = 8, Dx = 1.326 g cm–3, l(MoKa) = 0.7107 Å, m(MoKa) = 2.64 cm–1, F(000) = 1062, T = 294 K.Intensity data were collected on an Enraf-Nonius CAD-4 diffractometer using the q/2q scan method (2qmax = 54°). The structure was solved by the direct method (SHELXS-884) and refined by the full-matrix least-squares procedure (SHELXL-935) in an anisotropic approximation for all non-hydrogen atoms.The coordinates and thermal parameters of the hydrogen atoms were fixed (UH 0.08 Å2, C–H 0.096 Å). Final R1 = 0.052, wR2 = 0.137 and S = 1.071 for 3933 observed reflections with I > 2s(I). Atomic coordinates, bond lengths, bond angles and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre (CCDC).For details, see ‘Notice to Authors’, Mendeleev Commun., 1998, Issue 1. Any request to CCDC for data should quote the full literature citation and the reference number 1135/33. This study was supported by the Russian Foundation for Basic Research (grant no. 98-03-32689a) and the Special Federal Program ‘Integratsiya’ (grant no. K0512). References 1 A. M. Fivush and S. R. Strunk, Synth. Commun., 1996, 26, 1623. 2 Y. Nagao, W. S. Lee, I. Y. Jeong and M. Shiro, Tetrahedron Lett., 1995, 36, 2799. 3 V. A. Glushkov and Yu. V. Shklyaev, Mendeleev Commun., 1998, 17. 4 G. M. Sheldrick, Acta Crystallogr., 1990, 46A, 467. 5 G. M. Sheldrick, SHELXL-93, Program for the Refinement of Crystal Structures, University of Göttingen, Germany. Received: Moscow, 3rd July 1998 Cambridge, 30th September 1998; Com. 8/05570J

ISSN:0959-9436     

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) , '-Diamino- , '-dicarboxyadipic acid tetraester: synthesis, lactamisation and dilactam structure Remir G. Kostyanovsky,*a Yurii I. El’natanov,a Oleg N. Krutius,a Ivan I. Chervina and Konstantin A. Lyssenkob a N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 117977 Moscow, Russian Federation. Fax: +7 095 938 2156; e-mail: kost@center.chph.ras.ru b A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 117813 Moscow, Russian Federation. Fax: +7 095 135 5085; e-mail: kostya@xray.ineos.ac.ru a,a'-Diamino-a,a'-dicarboxyadipic acid tetraester has been synthesised for the first time; it spontaneously cyclises into a monolactam and, under the action of bases, into a dilactam; the latter forms in the crystal a heterochiral hydrogen-bonded polymer of the linear zig-zag type.Tetraesters of a,a'-dihydroxy-a,a'-dicarboxyadipic and -pimelic acids have been synthesised for the first time1 and their complete autoassembling into the corresponding dilactones was effected under the conditions of base or acid catalysis (prolonged storage at 20 °C or heating, respectively).2 The autoassembling of similar dilactams could be expected to occur substantially more easily, however, this is not the case. The above tetraacids were unknown until recently, although they are provoking interest as uncommon,3 unnatural and unusual a-amino acids.4–6 As we have shown earlier,7 the above acids could not be obtained from alkylene-bisbromomalonates. Numerous examples of the C-alkylation of N-acylaminomalonates8,9 seemed to be promising as an alternative method of synthesis.However, our attempts to obtain tetraesters of a,a'-diamino-a,a'-dicarboxyadipic acid 1 by reactions of 1,2-dihaloethanes (Hal = Cl, Br) with N-formyl- and N-acetylaminomalonates failed, as previously with N-benzoylaminomalonate.8 In this work diaminotetraester 1 was synthesised by reduction (SnCl2) of ethylene-bisazidomalonate (Scheme 1) which was itself obtained by reaction of azido transfer from tosyl azide to ethylene-bismalonate dianion.10 Diaminotetraester 1 forms stable salts (dihydrochloride and dipicrate) and undergoes a spontaneous monolactamisation under normal conditions.Dilactamisation also takes place under normal conditions on treatment with bases (DBU, Et3N and other amines).So, the reaction of 1 with 2 equivalents of MeNH2 (EtOH, 18 h, 20 °C) gives dilactam 3 in a yield of 74% and no noticeable formation of methylamides is observed. The composition and structure of all the products are confirmed by satisfactory elemental analyses and spectroscopic data† (cf. data for relative mono- and dilactones2,11 and unsubstituted dilactam12).The NMR spectra of dilactam 3 (Figure 1) point to chirality of the molecule (non-equivalence of the methylene protons of the CO2Et group) and its C2 symmetry [pairwise equivalence of protons and carbons as well as AA'BB' spectrum for the protons of the (CH2)2 bridge (Figure 1)]. This rigid bicyclic system is a matter of interest for crystal engineering by means of a stereoregular assembling of molecules using the hydrogen bonds.13–17 On the basis of data in ref. 12 we have predicted a regular crystal structure for dilactam 3 (cf. ref. 16). The molecular structure of 3 in the solid state was determined by an X-ray method‡ (Figure 2). The bond lengths and angles (Figure 2) in structure 3 have the expected values18 and are very similar to the corresponding values in the unsubstituted 2,5-diazabicyclo[2,2,2]octane-3,6-dione.12 The bicyclic molecule 3 features a synchro(-,-,-)-twist conformation (cf. similar dilactones19,20).The torsion angles C(4)– N(5)–C(6)–C(1), C(4)–C(3)–N(2)–C(1) and C(4)–C(8)–C(7)–C(1) are equal to –3.1°, –3.1° and –5.0°, respectively. Nitrogen atoms N(2) and N(5) of the amido groups are characterised by a planar conformation (the deviation of the nitrogens from the plane of the neighbouring atoms does not exceed 0.09 Å).It is noteworthy that (probably due to the packing effects in structure 3) the ethoxycarbonyl groups are disordered (Figure 2). The OCO fragments have a slightly different orientation, disturbing the local C2 symmetry of the rest of the molecule.The corre- a a a a [CH2C(CO 2Et)2]2 N3 [CH2C(CO 2Et)2]2 NH2 i ii N O He EtO 2C EtO 2C Hc Hd Hb Ha NH2 CO2Et A' B' A B HN NH O O iii EtO 2C CO 2Et 1 2 3 Scheme 1 Reagents and conditions: i, SnCl2 in abs. EtOH at –5 °C and 12 h at 20 °C, then NaHCO3 and extraction by MeCO2Et; ii, in pure form, 12 h at 20 °C; iii, cat. DBU in MeCN, 18 h at 20 °C. 123° 128° 2° 4.3 2.3 1.3 d/ppm Figure 1 1H NMR spectrum of 3 in CD3OD. C(14') C(14) C(13) C(13') O(6) C(12) O(5) C(4) N(5) O(2) C(8) C(7) C(6)C(3) O(1) C(1) O(3) C(9) N(2) O(4) C(10) C(10') C(11) C(11') Figure 2 The general view of 3. Selected bond lengths (Å): O(1)–C(3) 1.220(3), O(2)–C(6) 1.222(3), N(2)–C(3) 1.337(3), N(2)–C(1) 1.475(3), N(5)–C(6) 1.340(3), N(5)–C(4) 1.473(3); selected bond angles (°): C(3)– N(2)–C(1) 116.5(2), C(6)–N(5)–C(4) 116.8(2), O(3)–C(9)–O(4) 124.9(3), O(3)–C(9)–C(1) 122.9(3), O(4)–C(9)–C(1) 112.2(2), O(5)–C(12)–O(6) 125.4(3), O(5)–C(12)–C(4) 123.0(3), O(6)–C(12)–C(4) 111.7(2).Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) † 1: yield 63%, colourless oil. 1H NMR (400.13 MHz, CDCl3) d: 1.27 (t, 12H, 4Me, 3J 7.0 Hz), 1.93 (br.s, 4H, 2NH2), 1.96 [s, 4H, (CH2)2], 4.21 (q, 8H, 4CH2O). 13C NMR (100.61 MHz, CDCl3) d: 13.06 (qt, Me, 1J 126.4 Hz, 2J 2.9 Hz), 28.82 [tt, (CH2)2, 1J 132.2 Hz, 2J 5.8 Hz], 60.75 (tq, CH2O, 1J 148.2 Hz, 3J 4.4 Hz), 64.35 (s, CN), 170.33 (br. s, CO). MS (EI, 70 eV) m/z: 377 [M + 1] (1.0), 303 [M – CO2Et] (3.0), 286 [M – CO2Et – NH3] (100), 257 [M – CO2Et – NH3 – Et] (98). 1, dihydrochloride: yield 84%, mp 173–174 °C (decomp.). 1H NMR (400.13 MHz, CD3OD) d: 1.34 (t, 12H, 4Me, 3J 7.0 Hz), 2.36 [s, 4H, (CH2)2], 4.39 (m, 8H, 4CH2O). 1, dipicrate: yield 79%, mp 168–170 °C. 1H NMR (400.13MHz, CD3OD) d: 1.31 (t, 12H, 4Me, 3J 7.0 Hz), 2.40 [s, 4H, (CH2)2], 4.35 (m, 8H, 4CH2O), 8.77 (s, 4H, 2C6H2). 2: yield 76%, mp 74–76 °C (Et2O). 1H NMR (400.13 MHz, [2H8]toluene) d: 0.81, 0.83 and 0.91 (t, 3×3H, 3Me, 3J 7.0 Hz), 1.59 (ddd, 1H, Ha, 2Jab –14.0 Hz, 3J 7.0 Hz, 3J 4.6 Hz), 2.0 (br.s, 2H, H2N), 2.21 (ddd, 1H, Hb, 3Jbc 8.9 Hz, 3J 4.6 Hz), 2.45 (m, 1H, Hc), 2.48 (m, 1H, Hd), 3.77, 3.80 and 3.88 (m, 3×2H, 3CH2O), 6.9 (br. s, He). 13C NMR (100.61 MHz, [2H6]benzene) d: 13.8 [qt, 5,5-(MeCH2O2C)2, 1J 127.0 Hz, 2J 2.7 Hz], 14.0 (qt, 2-MeCH2O2C, 1J 127.0 Hz, 2J 2.7 Hz), 24.9 (ttd, 4-CH2, 1J 134.4 Hz, 2J 3.6 Hz, 3J 3.6 Hz), 30.3 (tt, 3-CH2, 1J 131.5 Hz, 2J 3.6 Hz), 61.8 (m, 2-C), 61.75 (tq, 2-MeCH2O2C, 1J 148.5 Hz, 2J 4.3 Hz), 62.44 and 62.7 [tq, 5,5-(MeCH2O2C)2, 1J 149.0 Hz, 2J 4.3 Hz], 66.7 (m, 5-C), 168.18 (m, CO, 3J 4.3 Hz), 168.37 (m, CO, 3J 3.6 and 2.9 Hz), 170.1 (br.s, CON), 173.6 (m, CO, 3J 3.6 and 2.9 Hz). MS (EI, 70 eV) m/z: 258 [M – C2H4 – CO2] (100), 243 (28), 183 (28), 155 (17), 137 (10), 128 (10), 116 (12), 111 (30), 100 (12), 42 (22), 29 (35), 28 (61). 2, hydrochloride: yield 90%, mp 126 °C (EtOH/Et2O). 3: yield 92.7%, mp 271 °C (MeCN). 1H NMR (400.13 MHz, CD3OD) d: 1.3 (t, 6H, 2Me, 3J 7.0 Hz), 2.3 [m, 4H, (CH2)2, AA'BB' spectrum, Dn 41.2, 2JAB –13.4 Hz, 2JA'B' –13.4 Hz, 3JAB' 10.8 Hz, 3JA'B 10.8 Hz, 3JBB' 4.5 Hz, 3JAA' 4.2 Hz], 4.3 (m, 4H, 2CH2O, ABX3 spectrum, Dn 7.0, 2JAB –11.1 Hz). 1H NMR (400.13 MHz, CDCl3) d: 1.39 (t, 6H, 2Me, 3J 7.0 Hz), 2.39 (m, 4H, 2CH2, AA'BB' spectrum, Dn 80.0), 4.40 (m, 4H, 2CH2O, ABX3 spectrum, Dn 13.0, 2JAB –12.0 Hz), 6.85 (br. s, 2H, HN). 13C NMR (100.61 MHz, [2H6]DMSO) d: 14.12 (qt, Me, 1J 126.4 Hz, 2J 2.9 Hz), 27.7 [t, (CH2)2, 1J 138.1 Hz], 62.0 (tq, CH2O, 1J 148.2 Hz, 2J 4.4 Hz), 65.31 (s, CCO2Et), 165.85 (CO2).MS (EI, 70 eV, resolution 5000, for M+ found: 284.1008, calc. for C12H16N2O6: 284.100836) m/z: 284 [M+] (48), 238 (38), 213 (20), 182 (12), 167 (25), 165 (57), 154 (13), 136 (12), 58 (46), 43 (100). sponding torsion angles O(5)–C(12)–C(4)–C(8) and O(3)–C(9)– C(1)–C(7) are –35.8° and –41.9°. The molecules in the crystal structure 3 are assembled into infinite zig-zag chains of alternating (+) and (–) enantiomers directed along the crystallographic axes a (Figure 3) through approximately equal centrosymmetric intermolecular H-bonds: N(2)–H(2)···O(1' ) (1 – x, 1 – y, –z) and N(5)–H(5)···O(2') (–x, 1 – y, –z) (the average N···O', H···O' distances and N–H–O' angle are 2.946 Å, 2.15 Å and 157°, respectively).Moreover, the (+) and (–) enantiomers are interlinked by the intermolecular contacts C(8)–H(8A)···O(2'') (–x, 2 – y, –z) [C(8)···O(2'') 2.422(4) Å, H(8A)···O(2'') 2.42 Å, C(8)–H(8A)–O(2'') 155.1°] forming layers parallel to crystallographic plane ab. These Csp3H–O contacts can be considered according to Desiraju’s classification,21 as contacts of moderate strength which play a significant role in the crystal packing.21 ‡ Crystallographic data for 3: C12H16N2O6, M = 284.1, monoclinic crystals, space group P21/n, a = 10.189(2) Å, b = 5.568(1) Å, c = 24.114(5) Å, b = 95.39(2)°, V = 1361.9(5) Å3, Z = 4, dcalc = 1.386 g cm–3, m(MoKa) = = 1.12 cm–1, F(000) = 600.Intensities of 2369 reflections were measured on a Siemens P3 diffractometer at 20 °C (lMoKa radiation, q/2q scan technique, 2q < 50°), and 2009 independent reflections were used in further calculations and refinement.The structure was solved by a direct method and refined using the full-matrix least-squares method against F2 in the anisotropic–isotropic approximation. Hydrogen atoms were located from the difference Fourier synthesis with the exception of the hydrogens of the ethyl groups, the positions of which were calculated and included in the further refinement using a riding motion model.The difference Fourier synthesis for 3 revealed additional peaks which were interpreted as a disorder of the ethyl groups by two positions with equal occupancies. The refinement is converged to wR2 = 0.1823 and GOF = 1.02 for all independent reflections [R1 = 0.0593 is calculated against F for 1520 observed reflections with I > 2s(I)].The number of refined parameters is 241. All the calculations were performed using SHELXTL PLUS 5.0 on an IBM PC/AT. Atomic coordinates, bond lengths, bond angles and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre (CCDC). For details, see ‘Notice to Authors’, Mendeleev Commun., 1998, Issue 1.Any request to the CCDC for data should quote the full literature citation and the reference number 1135/32. N(2') H(2') O(1') O(1) H(2) N(2) N(5) H(5) O(2) O(2') H(5') H(8A) O(2'') H(8A'') Figure 3 The formation of zig-zag chains and layers in structure 3. The ethoxycarbonyl groups and hydrogens which do not take part in the shortened contacts are omitted for clarity.Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) It should be noted that the present synthesis of 3 is the simplest method of functionalisation for the parent dilactam from this series (cf. ref. 22), derivatisation of 3 is in progress. This work was accomplished with financial support from the Russian Foundation for Basic Research (grant no. 97-03-33021). References 1 R. G. Kostyanovsky, Yu. I. El’natanov and O. N. Krutius, Izv. Akad. Nauk, Ser. Khim., 1994, 2190 (Russ. Chem. Bull., 1994, 43, 2070). 2 R. G. Kostyanovsky, Yu. I. El’natanov, O. N. Krutius and V. N. Voznesensky, Izv. Akad. Nauk, Ser. Khim., 1995, 327 (Russ. Chem. Bull., 1995, 44, 318). 3 E. A. Bell, FEBS Lett., 1976, 64, 29. 4 J. Brunner, Chem.Soc. Rev., 1993, 22, 183. 5 J. M. Humphrey and A. R. Chamberlin, Chem. Rev., 1997, 97, 2243. 6 K. Tanaka and H. Sawanishi, Tetrahedron Asymm., 1998, 9, 71. 7 R. G. Kostyanovsky, O. N. Krutius and Yu. I. El’natanov, Izv. Akad. Nauk, Ser. Khim., 1994, 2185 (Russ. Chem. Bull., 1994, 43, 2065). 8 C. E. Redemann and M. S. Dunn, J. Biol. Chem., 1939, 130, 341. 9 H. Schneider, G.Sigmund, B. Sehricker, K. Thirring and H. Berner, J. Org. Chem., 1993, 58, 683. 10 R. G. Kostyanovsky and O. N. Krutius, Izv. Akad. Nauk, Ser. Khim., 1996, 1036 (Russ. Chem. Bull., 1996, 45, 990). 11 R. G. Kostyanovsky and Yu. I. El’natanov, Izv. Akad. Nauk, Ser. Khim., 1994, 650 (Russ. Chem. Bull., 1994, 43, 599). 12 M.-J. Brienne, J. Gabard, M. Leclercq, J.-M. Lehn, M. Cesario, C. Pascard, M.Cheve and G. Dutruc-Rosset, Tetrahedron Lett., 1994, 35, 8157. 13 M. C. Etter, Acc. Chem. Res., 1990, 23, 120. 14 C. B. Aakeröy and K. R. Seddon, Chem. Soc. Rev., 1993, 22, 397. 15 E. Boucher, M. Simard and J. D. Wuest, J. Org. Chem., 1995, 60, 1408. 16 A. Gavezzotti, Acc. Chem. Res., 1994, 27, 309. 17 S. Palacin, D. N. Chin, E. E. Simanek, J. C.McDonald, G. M.Whitesides, M. T. McBride and G. T. R. Palmore, J. Am. Chem. Soc., 1997, 119, 11807. 18 F. H. Allen, O. Kennard, D. G. Watso, L. Brammer, A. G. Orpen and R. Taylor, J. Chem. Soc., Perkin Trans. 2, 1987, 1. 19 A. B. Zolotoi, S. V. Konovalikhin, L. O. Atovmyan, I. V. Vystorop, Yu. I. El’natanov and R. G. Kostyanovsky, Izv. Akad. Nauk, Ser. Khim., 1994, 1965 (Russ. Chem. Bull., 1994, 43, 1854). 20 A. Rauk, C. Jaime, I. V. Vystorop, V. M. Anisimov and R. G. Kostyanovsky, J. Mol. Struct. (Theochem), 1995, 342, 93. 21 G. R. Desiarju, Acc. Chem. Res., 1996, 29, 441. 22 M.-J. Brienne, J. Gabard, M. Leclercq, J.-M. Lehn and M. Cheve, Helv. Chim. Acta, 1997, 80, 856. Received: Moscow, 26th June 1998 Cambridge, 1st October 1998; Com. 8/05514I

ISSN:0959-9436     

出版商:RSC    

年代:1998

数据来源: RSC

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Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) Chiral glycouril, 2,6-diethyl-2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione: spontaneous resolution, reactivity and absolute configuration Remir G. Kostyanovsky,*a Konstantin A. Lyssenko,b Gulnara K. Kadorkina,a Oleg V. Lebedev,c Angelina N. Kravchenko,c Ivan I. Chervina and Vasily R. Kostyanovskya a N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 117977 Moscow, Russian Federation.Fax: +7 095 938 2156; e-mail: kost@center.chph.ras.ru b A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 117813 Moscow, Russian Federation. Fax: +7 095 135 5085; e-mail: kostya@xray.ineos.ac.ru c N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 118913 Moscow, Russian Federation.Fax: +7 095 135 5328 The title glycouril 1 was spontaneously resolved into enantiomers by crystallisation from H2O and sorting of conglomerate crystals, then N-chlorination and N-aminomethylation to give 2, 3 and 4, respectively, were studied. The absolute configuration 1R,5R-(+) was determined by an X-ray diffraction study of diastereomeric N,N-bis-aminomethyl derivative (–)-4.Racemic bicyclic bis-lactams (BBL) were observed to selfassemble into the hydrogen bonded heterochiral polymeric linear zig-zag (lz) chains in crystals (Scheme 1), with space groups Pccn (for R = H)1 and P21/n (for R = CO2Et).2 Therefore, these compounds cannot be spontaneously resolved by crystallisation. It can be assumed that chain termination of hydrogen bonded polymerisation takes place in the case of homochiral selfassembling. Indeed, in a crystal of (R,R)-(–)-BBL (R = H) (space group P21212) a cyclic tetramer rather than the expected hexamer (cy) is formed.1 However, a similar self-assembling could be arranged along the diagonal line, for example, in the case of bicyclic bis-ureas (BBU) (Scheme 1) where two possibilities of hydrogen bonded polymerization without chain termination exist.One of them is a heterochiral diagonal zig-zag (dz) like BBL, and the other is a homochiral helical structure (he). Exactly the latter possibility, though in a more complicated form, is realised for BBU. According to an X-ray diffraction study the chiral BBU, 2,6-diethyl-2,4,6,8-tetraazabicyclo[3.3.0]octane-3,7-dione 1 forms a conglomerate (space group P41212)3,4 whereas its complex 1·ZnCl2(H2O) has a centrosymmetric structure (space group P21/c).5 Thus, for the first time, spontaneous resolution of glycouril (±)-1 was brought about successfully by routine crystallisation from H2O followed by the sorting of levo- and dextro-rotatory crystals (Scheme 2).Crystallisation of (±)-1 in open vessels at slow self-evaporation gives large transparent sparkling crystals; the weight ranges from 10 to 50 mg and more and the size is up to 1 cm3.Aggregations are also formed, and their fracture results in enantiomeric, levo- and dextro-rotatory samples. Repeated crystallisations lead to optical enrichment, and substantial amounts of optically pure crystals of (+)- and (–)-1, which show maximum optical rotation values and constant melting points, were obtained.They are characterised by NMR and CD spectra† (Figure 1). Results of their study by X-ray diffraction are in agreement with the previous data.4 It is noteworthy that enantiomers 1 are less soluble in H2O and MeOH compared with racemic sample. After boiling of enantiomer 1 in concentrated HCl (1 h) complete decomposition of the sample (1H NMR) and loss of the optical activity are observed.In order to determine the absolute configuration of enantiomers 1 a search for suitable derivatives was carried out (Scheme 2). The heavy atom containing derivative, 2,6-dichloro-BBU (–)-2 was prepared by N-chlorination of (+)-1; however, it is rather unstable and decomposes during crystallisation attempts from a benzene–hexane mixture.N-Aminomethylation of (–)-1 gives the stable crystalline 2,6-bis-morpholinomethyl-BBU (+)-3 and oily diastereoisomer (+)-4 containing an S-(–)-proline residue. Crystalline diastereomer (–)-4 was obtained from (+)-1 and its N N R R O H O H N N R R O H O H ... ... ... ... ... ... N N R H... ... ... ... BBL R = H, CO2Et BBU N N O O H R ...... N N R H N N O O H R Linear zig-zag (lz) Diagonal zig-zag (dz) L D 120° Cycle (cy) Helix (he) 120° L D Scheme 1 L L L L L L L L L L L L L N N N N Et NR2 Et R2N O O N N N N Et H Et H O O R-(+)-3 iii S-(–)-1 iv N N N N Et NR2 Et R2N O O R-(+)-4 N N N N Et Cl Et Cl O O N N N N Et H Et H O O S-(–)-2 ii R-(+)-1 iv N N N N Et R2N Et NR2 O O S-(–)-4 (±)-1 i i O N R2N = R2N = N CO2Me H n n Scheme 2 Reagents and conditions: i, crystallisation from H2O and sorting of crystals; ii, ButOCl in CH2Cl2 , 24 h, 20 °C; iii, MeOCH2N(CH2CH2)2O and molecular sieves 4 Å in PriOH, 1 week, 20 °C; iv, S-(–)-MeOCH2- N(CH2)3CHCO2Me and molecular sieves 4 Å in PriOH, 1 week, 20 °C.Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) molecular structure (Figure 2) and the absolute configuration 1S,5S were determined by X-ray diffraction.‡ The results obtained are of importance for the chemistry of glycouril, which has been developing extensively during the last 120 years.6–8 First of all 2,4,6,8-tetraalkyl-BBUs exhibit high psychotropic activity,9 and glycouril 1 is a precursor of 2,6-diethyl-4,8-dimethyl-BBU known as the medicine Albicar.These results open up possibilities for synthesis of chiral drugs.10 Gompper’s group has studied the rearrangement reactions † The NMR spectra were measured on a Bruker WM-400 spectrometer (at 400.13 MHz for 1H and 100.62 MHz for 13C from TMS). Optical rotation was measured on a Polamat A polarimeter. The CD spectra were recorded on a JASCO J-500A instrument with a DP-500N data processor.(±)-1: obtained by the method described in ref. 4, mp 286–288 °C. 1H NMR (CD3OD) d: 1.14 (t, 6H, 2Me, 3J 7.0 Hz), 3.25 (m, 4H, 2CH2, ABX3 spectrum, Dn 84.0 Hz, 2J –14.0 Hz, 3J 7.0 Hz), 5.39 (s, 2H, 2CH). 13C NMR (CD3OD) d: 13.25 (qt, Me, 1J 126.4 Hz, 2J 2.9 Hz), 36.56 (tq, CH2, 1J 138.1 Hz, 2J 4.4 Hz), 67.49 (d, CH, 1J 167.1 Hz), 161.64 (tt, CO, 3J 2.9 Hz).lmax 216.2 nm (MeOH). R-(+)-1: mp 330–331 °C (decomp.), [a]D 20 = 101.4° (c 1.2 H2O), De = = +9.62 (lmax 198 nm). S-(–)-1: mp 330–331 °C (decomp.), [a]D 20 = –93.8° (c 0.19 MeOH), De = = –9.3 (lmax 198 nm). R-(+)-2: obtained from S-(–)-1 {[a]D 20 = –84.4° (c 0.58 MeOH)}, yield 96%, mp 122–129 °C, [a]D 20 = +46.1° (c 0.3 MeOH). 1H NMR (C6D6) d: 0.87 (t, 6H, 2Me, 3J 7.5 Hz), 3.08 (br.q, 4H, 2CH2, 3J 7.5 Hz), 3.94 (s, 2H, 2CH). S-(–)-2: obtained in a similar manner from R-(+)-1 {[a]D 20 = +87.5° (c 0.37 MeOH)}, [a]D 20 = –53.2° (c 1.67 MeOH). R-(+)-3: obtained from the partly enriched S-(–)-1 and N-methoxymethylmorpholine [1H NMR (CDCl3) d: 2.66 (m, 4H, 2CH2N), 3.31 (s, 3H, MeO), 3.69 (m, 4H, 2CH2O), 3.98 (s, 2H, OCH2N)], yield 47%, mp 144–146 °C (benzene–n-hexane), [a]D 20 = +25.6° (c 0.2 MeOH), ee ª ª 15% [as found from 1H NMR spectrum, in C6D6 with addition of Eu(tfc)3, by displacement of the CH2N signal (from 2.15 to 2.55 ppm) and its split (Dn = 42 Hz) into two signals in a ratio of 1.35]. 1H NMR (C6D6) d: 0.96 (t, 6H, 2Me, 3J 7.0 Hz), 2.15 (m, 8H, 4CH2N), 3.39 (m, 2CH2Me, ABX3 spectrum, Dn 256.0 Hz, 2J –14.0 Hz, 3J 7.0 Hz), 3.45 (m, 8H, 4CH2O), 3.72 (m, 4H, 2NCH2N, AB spectrum, Dn 168.0 Hz, 2J –12.2 Hz). 13C NMR (CDCl3) d: 12.42 (q, Me, 1J 126.4 Hz), 37.02 (tq, CH2Me, 1J 138.1 Hz, 2J 4.4 Hz), 50.57 (t, NCH2C, 1J 133.7 Hz), 65.16 (t, NCH2N, 1J 145.3 Hz), 66.14 (d, CH, 1J 165.7 Hz), 66.38 (t, CH2O, 1J 142.4 Hz), 157.55 (s, CO). S-(–)-4: obtained from R-(+)-1 {[a]D 20 = +95.8° (c 0.24 MeOH)} and S-(–)-methyl 1-methoxymethylprolinate {[a]D 20 = –58.3° (c 1.3 MeOH)}, yield 34%, mp 98.5 °C (benzene–n-hexane), [a]D 20 = –122.5° (c 0.6 MeOH). 1H NMR (C6D6) d: 1.17 (t, 6H, 2Me, 3J 7.0 Hz), 1.38, 1.56–1.72 and 1.80 [m, 8H, 2(CH2)2CH], 2.43 and 2.87 (m, 4H, 2CH2N), 3.01 (dd, 2H, 2HCN, 3J 6.3 and 8.9 Hz), 3.28 (s, 6H, 2MeO), 3.55 (m, 4H, 2CH2Me, ABX3 spectrum, Dn 168.0 Hz, 2J –12.0 Hz, 3J 7.0 Hz), 4.20 (m, 4H, 2NCH2N, AB spectrum, Dn 252.0 Hz, 2J –14.0 Hz), 5.36 (s, 2H, 2CH).R-(+)-4: obtained from S-(–)-1 {[a]D 20 = –89.5° (c 0.83 MeOH)} and S-(–)-methyl 1-methoxymethylprolinate, yield 82.6%, oil, [a]D 20 = +7.23° (c 1.9 MeOH). 1H NMR (C6D6) d: 1.14 (t, 6H, 2Me, 3J 7.0 Hz), 1.28, 1.56 and 1.73 [m, 8H, 2(CH2)2CH], 2.19 and 2.82 (m, 4H, 2CH2N), 3.30 (m, 2H, 2CHN), 3.36 (s, 6H, 2MeO), 3.50 (m, 4H, 2CH2Me, ABX3 spectrum, Dn 196.0 Hz, 2J –14.0 Hz, 3J 7.0 Hz), 4.15 (m, 4H, 2NCH2N, AB spectrum, Dn 224.0 Hz, 2J –12.0 Hz), 5.55 (s, 2H, 2CH).‡ Crystallographic data for (–)-4: C22H36N6O6, M = 480.57, monoclinic crystals, space group P21, a = 9.616(3) Å, b = 8.952(3)Å, c = 14.783(5) Å, b = 98.14(3)°, V = 1259.6(7) Å3, Z = 4, dcalc = 1.267 g cm–3, m(MoKa) = = 0.94 cm–1, F(000) = 516.Intensities of 2859 reflections were measured on a Siemens P3 diffractometer at 20 °C (lMoKa radiation, q/2q scan technique, 2q < 52°) and were used in further calculations and refinement. The absolute configuration 1S,5S for the molecule of (–)-4 was confirmed on the basis of the known configuration (S) of the proline moiety. The structure was solved by a direct method and refined by full-matrix least-squares against F2 in the anisotropic–isotropic approximation.The positions of the hydrogen atoms were calculated. The refinement converged to wR2 = 0.2123 and GOF = 1.043 for all 2698 independent reflections [R1 = 0.0595 is calculated against F for the 1663 observed reflections with I > 2s(I)]. The number of the refined parameters is 307.All calculations were performed using SHELXTL PLUS 5.0 on an IBM PC/AT. Atomic coordinates, bond lengths, bond angles and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre (CCDC). For details, see ‘Notice to Authors’, Mendeleev Commun., 1998, Issue 1. Any request to the CCDC for data should quote the full literature citation and the reference number 1135/34.of glycouril derivatives, and based on them new tricyclic cis-diaziridines and polyaza heterocycles were synthesised.11 In 10 8 6 4 2 0 –2 –4 –6 –8 –10 200 220 l/nm De Figure 1 CD spectra of R-(+)-1 (top) and S-(–)-1 (bottom). C(1) C(2) C(3) C(4) C(5) C(6) C(7) C(8) C(9) C(10) C(11) C(12) C(13) C(14) C(15) C(16) C(17) C(18) C(19) C(20) C(21) C(22) O(1) O(2) O(3) O(4) O(5) O(6) N(1) N(2) N(3) N(4) N(5) N(6) Figure 2 General view of the molecule (–)-4.Only hydrogens linked with asymmetric carbon atoms are shown. Selected bond lengths (Å): O(1)–C(3) 1.223(5), N(1)–C(1) 1.449(6), N(1)–C(3) 1.368(6), N(1)–C(5) 1.451(7), N(2)–C(2) 1.431(5), N(2)–C(3) 1.367(6), N(2)–C(21) 1.441(7), N(5)–C(5) 1.447(8), C(1)–C(2) 1.549(6); selected bond angles (°): C(3)–N(1)–C(1) 112.4(4), C(3)–N(1)–C(5) 122.3(4), C(1)–N(1)–C(5) 121.7(4), C(3)–N(2)– C(2) 112.5(4), C(3)–N(2)–C(21) 121.9(4), C(2)–N(2)–C(21) 125.2(4), N(3)– C(1)–N(1) 115.2(4), N(3)–C(1)–C(2) 103.4(4), N(1)–C(1)–C(2) 102.8(3), N(2)–C(2)–N(4) 115.9(4), N(2)–C(2)–C(1) 103.8(3), N(4)–C(2)–C(1) 103.4(3), O(1)–C(3)–N(2) 125.3(4), O(1)–C(3)–N(1) 126.7(4), N(2)– C(3)–N(1) 108.0(4), N(5)–C(5)–N(1) 112.1(4).Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) the extensive studies of Rebek’s group12–16 and Nolte’s group17 achiral glycourils have been examined as structural units for the design of self-assembling molecular clips and capsules. A glycouril-based system (cucurbituril) was used by Kim’s group in the elegant design of a coordination polymeric polyrotaxane18 and polycatenated polyrotaxane.19 Readily accessible enantiomeric glycourils can give new, strong impetus to the synthesis of chiral supramolecular systems and can be used as new chiral reagents in asymmetric halogenation and aminomethylation reactions.This work was supported by the Russian Foundation for Basic Research (grant nos. 97-03-33021, 97-03-33786 and 96-15-97367).References 1 M.-J. Brienne, J. Gabard, M. Leclercq, J.-M. Lehn, M. Cesario, C. Pascard, M. Cheve and G. Dutruc-Rosset, Tetrahedron Lett., 1994, 35, 8157. 2 R. G. Kostyanovsky, Yu. I. El’natanov, O. N. Krutius, I. I. Chervin and K. A. Lyssenko, Mendeleev Commun., 1998, 228. 3 M. G. Tsintsadze, A. Yu. Tsivadze, A. A. Dvorkin and T. B. Markova, Soobshcheniya AN GSSR, 1986, 121, 553 (in Russian). 4 E. B. Shamuratov, A. S. Batsanov, Yu. T. Struchkov, A. Yu. Tsivadze, M. G. Tsintsadze, L. I. Khmel’nitskii, Yu. A. Simonov, A. A. Dvorkin, O. V. Lebedev and T. B. Markova, Khim. Geterotsikl. Soedin., 1991, 937 [Chem. Heterocycl. Compd. (Engl. Transl.), 1991, 745]. 5 V. B. Rybakov, L. A. Aslanov, M. G. Tsintsadze and A. Yu. Tsivadze, Zh. Strukt. Khim., 1989, 30, 175 [J.Struct. Chem. (Engl. Transl.), 1989, 30, 151]. 6 H. Petersen, Synthesis, 1973, 243. 7 P. H. Boyle and E. O’Brien, Proc. Roy. Irish Acad., 1983, 83B, 13. 8 A. A. Bakibaev, A. Yu. Yagovkin and S. N. Vostretsov, Usp. Khim., 1998, 67, 333 (Russ. Chem. Rev., 1998, 67, 295). 9 O. V. Lebedev, L. I. Khmel’nitskii, L. V. Epishina, L. I. Suvorova, I. V. Zaikonnikova, I.E. Zimakova, S. V. Kirshin, A. M. Karpov, V. S. Chudnovskii, M. V. Povstyanoi and V. A. Eres’ko, in Tselenapravlennyi Poisk Novykh Neirotropnykh Preparatov (Purposeful Search for New Neurotropic Medicines), Zinatne, Riga, 1983, p. 81 (in Russian). 10 (a) S. C. Stinson, Chem. Eng. News, 1992, 70, 46; (b) S. C. Stinson, Chem. Eng. News, 1995, 73, 44; (c) S. C. Stinson, Chem. Eng. News, 1997, 75, 38. 11 R. Gompper, H. Nöth and P. Spes, Tetrahedron Lett., 1988, 29, 3639. 12 M. M. Conn and J. Rebek, Jr., Chem. Rev., 1997, 97, 1647. 13 D. M. Rudkevich and J. Rebek, Jr., Angew. Chem., Int. Ed. Engl., 1997, 36, 846. 14 Y. Tokunaga, D. M. Rudkevich and J. Rebek, Jr., Angew. Chem., Int. Ed. Engl., 1997, 36, 2656. 15 Y. Tokunaga and J. Rebek, Jr., J. Am. Chem. Soc., 1998, 120, 66. 16 J. M. Rivera, T. Martin and J. Rebek, Jr., J. Am. Chem. Soc., 1998, 120, 819. 17 R. J. Jansen, A. E. Rowan, R. de Gelder, H. W. Scheeren and R. J. M. Nolte, J. Chem. Soc., Chem. Commun., 1998, 121. 18 D. Whang, Y.-M. Jeon, J. Neo and K. Kim, J. Am. Chem. Soc., 1996, 118, 11333. 19 D. Whang and K. Kim, J. Am. Chem. Soc., 1997, 119, 451. Received: Moscow, 11th August 1998 Cambridge, 11th September 1998; Com. 8/06557H

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出版商:RSC    

年代:1998

数据来源: RSC

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Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) Reaction of N,N-dimethylaniline with 1,5-diferrocenyl-3-methyl-2,4-trimethylenepenta- 1,4-dienyl carbocation. A nonsynchronous cationic cyclodimerization mechanism in conjugated dienes Elena I. Klimova,*a Tatiana Klimova Berestneva,a Marcos G. Martínezb and Lena Ruíz-Ramireza a Department of Chemistry, National Autonomous University of Mexico, CP 04510 México, México.Fax: +5 25 622 5366; e-mail: klimova@servidor.unam.mx b Institute of Chemistry, National Autonomous University of Mexico, CP 04510 México, México Reaction of the 1,5-diferrocenyl-3-methyl-2,4-trimethylenepenta-1,4-dienyl tetrafluoroborate cation with N,N-dimethylaniline affords a mixture of products from the alkylation of N,N-dimethylaniline at the para-position by monomeric and linear and cyclic dimeric carbocations along with linear and cyclic dimers of 1,3-diferrocenylmethylene-2-methylenecyclohexane. These results confirm and illustrate a nonsynchronous cationic cyclodimerization mechanism for ferrocenylbuta-1,3-dienes.The idea that a stepped mechanism is involved in the cationic cyclodimerization of conjugated dienes was put forward by Hoffmann et al.1–3 in their study on the cyclodimerization reaction of 2,4-dimethylpenta-1,3-diene in the presence of acids.However, up to now this mechanism has not been unambiguously confirmed, although early experimental results are in agreement with it.4–6 Some recent results7–16 on the method of synthesis and on the chemical and structural properties of ferrocenyl-containing 1,3-dienes shed additional light on the reaction mechanism. The methylferrocenyl cations are deprotonated during interaction with nucleophiles (N,N-dimethylaniline, pyridine) resulting in the formation of intermediate ferrocenyl- 1,3-dienes followed by their subsequent cationic cyclodimerization. The proposed stepped cationic cyclodimerization mechanism was confirmed by the presence of ferrocenyl-1,3-diene dimers with a terpenoid or condensed polycyclic structure, as final products of the reaction.The presence of the intermediate linear dimeric ferrocenylallyl cation was confirmed in just two cases: in the cationic cyclodimerization of 2-methylene-3-ferrocenylmethylenecamphane and in 3-methylene-2-ferrocenylmethylenequinuclidine. 10,11,14 In our opinion, the absence of cyclic dimers in the above cases could be explained by steric hindrance in the camphane and quinuclidine fragments and/or by electronic factors that do not favour the intramolecular alkylation of the dimer cation 1, which would result in the less stable cation 2 (Scheme 1). However, it is worth noting that we could never prove the presence of cyclic intermediate cations, although we obtained cyclic dimers as final products, which indirectly indicates their presence in the intermediate steps of the reaction.In this work, we studied the reaction of the 1,5-diferrocenyl- 3-methyl-2,4-trimethylenepenta-1,4-dienyl tetrafluoroborate cation 1, which has not been described previously, with N,N-dimethylaniline. Carbocation 1 is of interest, because at all stages in the cationic cyclodimerization, it should form the stable dimeric (linear and cyclic) allyl carbocations.17,18 One could therefore expect that these carbocations could be observed in the reaction mixture by reaction with N,N-dimethylaniline. The final products of this reaction could prove the simultaneous existence of these cations and the stepped mechanism of the cationic cyclodimerization. In order to verify the validity of the above suggestion we obtained the tetrafluoroborate of carbocation 3 from the corresponding carbinol 4 by treatment with HBF4 etherate.7,12 This salt is rather stable upon storage under standard conditions (remains unchanged at room temperature for 10–12 h) (Scheme 2).† Indeed, treatment of salt 3 with N,N-dimethylaniline‡ results mainly in the formation of products 6–10§ from the alkylation of N,N-dimethylaniline at the para-position by all allyl (monomeric and dimeric) cations present in the equilibrium reaction mixture (Scheme 3).In addition, minor quantities of the linear and cyclic dimers 11, 12 and 13 were isolated from the reaction mixture (Scheme 4).† 1,5-Diferrocenyl-3-methylpenta-1,4-dienylcation tetrafluoroborate 3: yield 87%, black crystals, mp 221–230 °C (decomp.). 1H NMR (CD2Cl2) d: 2.13 (s, 3H), 2.71 (t, 2H, J 6.2 Hz), 3.49 (m, 4H, J 6.2 Hz), 5.10 (s, 4H, C5H4), 5.50 (s, 4H, C5H4), 5.31 (s, 5H, C5H5), 5.32 (s, 5H, C5H5), 8.33 (s, 2H). Found (%): C, 60.59; H, 5.24; F, 12.96; Fe, 19.16. Calc. for C29H29BF4Fe2 (%): C, 60.46; H, 5.07; B, 1.88; F, 13.20; Fe, 19.39. 2,6-Diferrocenylmethylene-1-methylcyclohexanol 4: yield 78%, yellow crystals, mp 156–157 °C. 1H NMR (CDCl3) d: 1.55 (s, 3H), 1.65 (s, 1H, OH), 2.21 (m, 2H, J 10.8, 4.2 Hz), 3.35 (m, 4H, J 10.8, 4.2 Hz), 4.1 (s, 10H, 2C5H5), 4.18 (s, 4H, C5H4), 4.27 (s, 2H, C5H4), 4.31 (s, 2H, C5H4), 6.42 (s, 2H). Found (%): C, 68.64; H, 6.12; Fe, 21.93. Calc.for C29H30Fe2O (%): C, 68.80; H, 5.98; Fe, 22.06. ‡ N,N-dimethylaniline (0.72 g, 6 mmol) was added to a solution of compound 3 (2.30 g, 4 mmol) in anhydrous CH2Cl2 (70 ml) with constant stirring in a dry inert atmosphere. The mixture was stirred at room temperature for 1 h, then the excess of N,N-dimethylaniline was washed out with water, a 1% solution of HCl and water again. The organic layer was separated and dried with Na2SO4.The solvent was distilled off in vacuo. The residue was chromatographed on a column filled with Al2O3 (III Brockmann activity). The following four fractions were obtained: Hexane as the eluent: fraction I (0.21 g); fraction II (0.56 g). Benzene– hexane (1:2) as second eluent: fraction III (1.02 g). Benzene–hexane (4:1) as third eluent: fraction IV (0.80 g).Then each fraction was chromatographed on SiO2 plates to obtain: from fraction I, 0.137 g (7%) of dimer 11 (hexane, Rf = 0.7); from fraction II, 0.098 g (5%) of dimer 12 (Rf = 0.63) and 0.195 g (10%) of dimer 13 (Rf = 0.54, benzene– hexane 1:2); from fraction III, 0.29 g (12%) of compound 7, (Rf = 0.51) and 0.49 g (20%) of compound 6, (Rf = 0.38, benzene–hexane 2:1); from fraction IV, 0.13 g (6%) of 10 (Rf = 0.41) and 0.20 g (9%) of 9 (Rf = 0.35) and 0.31 g (14%) of 8 (Rf = 0.28, benzene–hexane 3:1).N Me Fc N FcHC N Me N Fc Fc 1 2 Scheme 1 O FcHC CHFc MeLi FcHC CHFc Me OH Et2O·HBF4 Me FcHC CHFc Fc = C5H5FeC5H4 519 4 3 BF4 Scheme 2Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) All reaction products were separated by column chromatography on Al2O3 and then by preparative TLC on SiO2 and characterised by elemental analysis data and 1H and 13C NMR spectroscopy.According to the NMR data the dimerization and cyclodimerization occur diastereoselectively. Compounds 8–13 were § 1-p-Dimethylaminophenylferrocenylmethyl-3-ferrocenylmethylene-2- methylcyclohexene 6: orange crystals, mp 178–179 °C. 1H NMR (CDCl3) d: 1.49–1.66 (m, 2H), 1.85–2.04 (m, 2H), 2.4–2.6 (m, 2H), 2.08 (s, 3H, Me), 2.93 (s, 6H, 2Me), 4.10 (s, 5H, C5H5), 3.97 (m, 1H), 4.08 (m, 1H), 4.13 (m, 2H), 4.19 (m, 2H), 4.32 (m, 1H), 4.34 (m, 1H, 2C5H4), 5.17 (s, 1H, CH), 6.19 (s, 1H, CH=), 6.69 (d, 2H, J 8.2 Hz), 7.14 (d, 2H, J 8.2 Hz, C6H4). 13CNMR (CDCl3) d: 14.80 (Me), 23.23, 28.30, 28.42 (CH2), 40.74 (2Me), 47.49 (CH), 68.75 (C5H5), 68.98 (C5H5), 66.51, 67.35, 68.16, 68.18, 68.46, 69.45, 69.50, 69.72 (2C5H4), 83.96, 91.78 (CipsoFc), 112.28 (CH=), 119.46, 127.40, 129.06, 129.07 (C6H4), 131.49, 137.26, 139.77, 139.78, 148.89 (C).Found (%): C, 73.11; H, 6.34; Fe, 18.20, N, 2.09. Calc. for C37H39Fe2N (%): C, 79.92; H, 6.45; Fe, 18.33; N, 2.30. 1,3-Diferrocenylmethylene-2-p-dimethylaminophenyl-2-methylcyclohexane 7: orange crystals, mp 164–165 °C. 1HNMR (CDCl3) d: 1.50–1.68 (m, 2H), 1.81–2.02 (m, 2H), 2.41–2.61 (m, 2H), 2.05 (s, 3H, Me), 3.00 (s, 6H, 2Me), 4.12 (s, 5H), 4.13 (s, 5H, 2C5H5), 3.87 (m, 1H), 3.95 (m, 2H), 3.96 (m, 2H), 4.03 (m, 1H), 4.39 (m, 1H), 4.40 (m, 1H, 2C5H4), 6.28 (s, 2H, CH=), 6.79 (d, 2H, J 8.4 Hz), 7.24 (d, 2H, C6H4, J 8.4 Hz). 13C NMR (CDCl3) d: 14.13 (Me), 22.97, 28.89, 30.32 (CH2), 40.78 (2Me), 60.39 (C), 68.74 (C5H5), 69.05 (C5H5), 66.38, 67.19, 68.12, 68.13, 68.26, 69.35, 68.66, 68.90 (2C5H4), 77.21, 91.50 (CipsoFc), 112.27 (CH=), 119.45, 127.38, 129.0, 130.01 (C6H4), 131.02, 137.02, 137.24, 139.75, 148.79 (C).Found (%): C, 72.81; H, 6.58; Fe, 18.47, N, 2.12. Calc. for C37H39Fe2N (%): C, 72.92; H, 6.45; Fe, 18.33; N, 2.30.Spiro[3-p-dimethylaminophenylferrocenylmethyl-2-methyl-2-cyclohexene- 1,2'-(1,3-diferrocenyl-5-ferrocenylmethylene-1,2,3,4,5,6,7,8-octahydronaphthalene)] 8: yellow crystals, mp 241–242 °C. 1H NMR (CDCl3) d: 1.30–1.85 (m, 4H), 2.42–2.83 (m, 4H), 2.88–3.22 (m, 4H), 3.71 (d, 2H, J 7.2 Hz), 2.03 (s, 3H, Me), 2.92 (s, 6H, 2Me), 3.86 (t, 1H, J 7.2 Hz), 4.11, 4.15, 4.16, 4.17 (s, 4C5H5), 4.01 (m, 2H), 4.03 (m, 2H), 4.13 (m, 2H), 4.21 (m, 2H), 4.23 (m, 2H), 4.25 (m, 2H), 4.38 (m, 2H), 4.40 (m, 2H, 4C5H4), 4.84 (s, 1H, CHFc), 6.27 (s, 1H, CH=), 6.56 (d, 2H, J 8.7 Hz), 6.39 (d, 2H, C6H4, J 8.7 Hz). 13C NMR (CDCl3) d: 18.73 (Me), 22.66, 23.79, 26.16, 28.30, 32.06, 33.91, 40.88 (7CH2), 46.35 (2Me), 41.07, 45.93, 51.85 (3CH), 48.41 (C), 68.38, 68.82, 68.84, 69.07 (4C5H5), 65.95, 66.33, 66.49, 66.52, 66.68, 66.70, 68.22, 68.41, 68.57, 69.29, 69.37, 69.40, 69.59, 69.64, 70.06, 71.36 (4C5H4), 83.92, 91.70, 92.14, 93.55 (CipsoFc), 112.97 (CH=), 128.11, 129.34, 136.11, 136.19 (C6H4), 130.39, 132.82, 134.86, 137.06, 137.52, 139.56, 148.54 (C). Found (%): C, 72.43; H, 5.98; Fe, 20.21, N, 1.42.Calc. for C66H67Fe4N (%): C, 72.22; H, 6.15; Fe, 20.35; N, 1.28.Spiro[2-p-dimethylaminophenyl-3-ferrocenylmethylene-2-methylcyclohexane- 1,2'-(1,3-diferrocenyl-5-ferrocenylmethylene-1,2,3,4,5,6,7,8-octahydronaphthalene)] 9: yellow crystals, mp 210–211 °C. 1HNMR (CDCl3) d: 1.25–1.49 (m, 4H), 1.72–1.86 (m, 4H), 2.41–2.83 (m, 4H), 2.02 (s, 3H, Me), 2.96 (s, 6H, 2Me), 3.62 (d, 2H, J 6.9 Hz), 3.72 (t, 1H, J 6.9 Hz), 4.09, 4.12, 4.13, 4.15 (s, 4C5H5), 3.98 (m, 2H), 3.99 (m, 2H), 4.05 (m, 2H), 4.08 (m, 2H), 4.10 (m, 2H), 4.14 (m, 2H), 4.18 (m, 2H), 4.29 (m, 2H, 4C5H4), 4.92 (s, 1H, CHFc), 6.22 (s, 1H, CH=), 6.41(s, 1H, CH=), 6.63 (d, 2H, J 9.0 Hz), 6.92 (d, 2H, C6H4, J 9.0 Hz). 13C NMR (CDCl3) d: 15.56 (Me), 23.78, 25.01, 26.18, 28.30, 29.14, 32.60, 34.02 (CH2), 40.80 (2Me), 47.33, 47.97, 65.74 (CH), 48.43, 50.03 (C), 68.31, 68.71, 68.85, 69.27 (4C5H5), 66.49, 66.61, 67.90, 67.15, 67.41, 68.17, 68.45, 68.57, 68.65, 68.72, 69.19, 69.40, 69.65, 70.12, 70.74, 71.30 (4C5H4), 83.93, 90.67, 92.14, 93.52 (CipsoFc), 112.15, 117.60 (2CH=), 128.11, 129.87, 136.10, 136.20 (C6H4), 131.09, 131.12, 134.87, 139.05, 140.83, 148.60 (C).Found (%): C, 72.11; H, 6.23; Fe, 20.56, N, 1.05. Calc. for C66H67Fe4N (%): C, 72.22; H, 6.15; Fe, 20.35; N, 1.28. 1-p-Dimethylaminophenylferrocenylmethyl-3-ferrocenylmethylene-2- [2-ferrocenyl-2-(3-ferrocenylmethylene-2-methylcyclohex-1-enyl)]ethylcyclohexene 10: orange oil, 1H NMR (CDCl3) d: 1.26–1.49 (m, 4H), 1.72–1.86 (m, 4H), 2.52–2.71 (m, 4H), 3.20 (d, 2H, J 9.1 Hz), 3.85 (t, 1H, J 9.1 Hz), 2.03 (s, 3H, Me), 3.02 (s, 6H, 2Me), 4.74 (s, 1H, CHFc), 4.11, 4.13, 4.16, 4.17 (s, 4C5H5), 3.99–4.29 (m, 16H, 4C5H4), 6.24 (s, 1H, CH=), 6.31 (s, 1H, CH=), 6.62 (d, 2H, J 8.3 Hz), 6.79 (d, 2H, C6H4, J 8.3 Hz). 13CNMR (CDCl3) d: 18.74 (Me), 19.40, 20.01, 21.35, 24.93, 26.10, 27.18, 30.83 (CH2), 41.08 (2Me), 47.30, 48.56 (CH), 68.41, 68.56, 68.85, 69.10 (4C5H5), 65.71, 66.18, 66.58, 66.81, 67.22, 67.89, 68.24, 68.32, 68.76, 69.41, 70.04, 70.31, 70.50, 70.72, 71.26, 71.35 (4C5H4), 83.81, 83.86, 83.92, 92.14, (CipsoFc), 112.15 (CH=), 113.60 (CH=), 128.10, 129.87, 130.39, 136.19 (C6H4), 129.80, 130.38, 131.20, 131.22, 134.86, 136.20, 138.60, 147.68 (C).Found (%): C, 72.36; H, 5.91; Fe, 20.39, N, 1.41. Calc. for C66H67Fe4N (%): C, 72.22; H, 6.15; Fe, 20.35; N, 1.28. isolated in just one diastereoisomeric form. However, their spatial structures are not established yet.The parameters of the 1H NMR spectra (number of proton signals, values of chemical shifts and of spin–spin interaction constants) for the aliphatic and olefinic protons in compounds 3–13 confirm the suggested chemical structure of these compounds. Additional information on the structure of compounds 8–13 is obtained from the 13C NMR spectra.The presence of four quaternary carbon atom signals in the ferrocenyl fragments of compounds 8–13, together with the signals from four C5H5 groups, unambiguously prove the formation of dimers. The presence of Cspiro signals confirms the suggested cyclic structure of compounds 8, 9, 12 and 13. The number of 13C NMR signals from the C, CH, CH2 and Me groups in compounds 6–13 correspond to their chemical structure.§,¶ The formation of compounds 6 and 7 (products of alkylation of N,N-dimethylaniline) is sufficiently evident and does not require any additional justification.The existence of compounds 8–10 is explained well by the schemes discussed in refs. 1–12, which include the following stages: 1) deprotonation of the starting carbocation 3 via the intermediate formation of s-cis-diferrocenyltriene 14 [Scheme 5, (a)]; 2) formation of a linear dimeric cation 15 due to the addition of carbocation 3 to the triene 14 at the free methylene group [Scheme 5, (b)]; 3) formation of the cyclic allyl cation 16 by intramolecular alkylation of cation 15 [Scheme 5, (c)].Scheme 3 NMe2 3 + Me FcHC CHFc NMe2 Me FcHC CHFc NMe2 Fc CHFc Me Fc Fc Me2N CH Fc CHFc Me Fc Fc NMe2 Me CHFc Fc FcHC NMe2 Fc 10 9 8 6 7 CHFc Me Fc Fc CHFc CHFc Fc CHFc CHFc Fc CHFc Fc Fc CH2 11 12 13 Scheme 4Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) We believe that in this reaction, the alkylation of N,N-dimethylaniline at the para-position by carbocations 3, 15, 16a and 16b, and deprotonation of the same cations by a base, occur competitively, resulting in the formation of a mixture of all possible reaction products 6–13.We failed to detect the presence of the triene 14 in this process, most likely due to its low stability. However, we isolated the cyclodimer 12, which is a classic [4+2]-cycloaddition adduct of the Diels–Alder type. Thus, these results unambiguously confirm the previously suggested scheme1–12 for the nonsynchronous cationic cyclodimerization of buta-1,3-dienes.¶ 1,3-Diferrocenylmethylene-2-[2-ferrocenyl-2-(3-ferrocenylmethylene- 2-methylcyclohex-1-enyl)]ethylidenecyclohexane 11: orange crystals, mp 226–227 °C. 1H NMR (CDCl3) d: 1.30–1.65 (m, 4H), 1.83–2.10 (m, 2H), 2.21–2.40 (m, 2H), 2.51–3.05 (m, 4H), 1.76 (s, 3H, Me), 4.52 (d, CHFc, J 8.2 Hz) 4.02, 4.12, 4.15, 4.17 (s, 4C5H5), 3.62 (m, 2H), 3.78 (m, 2H), 3.87 (m, 2H), 3.90 (m, 2H), 4.30 (m, 4H), 4.35 (m, 4H, 4C5H4), 6.16 (d, 1H, CH=, J 8.24 Hz), 6.32 (s, 1H, CH=), 7.35 (s, 2H, CH=).Found (%): C, 71.43; H, 5.56; Fe, 23.03. Calc. for C58H56Fe4 (%): C, 71.34; H, 5.78; Fe, 22.88. Spiro[2,6-diferrocenylmethylenecyclohexane-1,2'-(1-ferrocenyl-5-ferrocenylmethylene- 1,2,3,4,5,6,7,8-octahydronaphthalene)] 12: yellow crystals, mp 236–237 °C. 1H NMR (CDCl3) d: 1.80–2.00 (m, 4H), 2.12–3.15 (m, 12H), 4.21 (s, 1H, CHFc), 4.05, 4.06, 4.09, 4.13 (s, 4C5H5) , 3.96 (m, 1H), 3.98 (m, 1H), 4.01 (m, 1H), 4.02 (m, 1H), 4.11 (m, 2H), 4.14 (m, 1H), 4.16 (m, 2H), 4.18 (m, 4H), 4.24 (m, 1H), 4.31 (m, 1H, 4C5H4), 5.56 (s, 1H), 5.91 (s, 1H), 6.15 (s, 1H, CH=). 13C NMR (CDCl3) d: 22.68, 23.55, 26.13, 26.92, 28.19, 29.58, 31.88, 33.56 (CH2), 46.55 (C), 52.28 (CHFc), 68.73, 68.87, 69.00, 69.05 (4C5H5), 65.59, 67.42, 67.48, 67.68, 67.75, 67.79, 67.83, 68.02, 68.11, 68.78, 68.96, 69.19, 69.26, 69.28, 69.32, 69.40, 69.64 (4C5H4), 83.88, 84.08, 84.28, 89.32 (CipsoFc), 116.48, 117.71, 118.78 (3CH=), 129.36, 135.60, 136.49, 144.02, 145.43 (C).Found (%): C, 71.49; H, 5.52; Fe, 23.01.Calc. for C58H56Fe4 (%): C, 71.34; H, 5.78; Fe, 22.88. Spiro[3-ferrocenylmethylene-2-methylenecyclohexane-1,2'-(1,3-diferrocenyl- 5-ferrocenylmethylene-1,2,3,4,5,6,7,8-octahydronaphthalene)] 13: yellow crystals, mp 262–263 °C. 1HNMR (CDCl3) d: 1.68–2.06 (m, 4H), 2.18–2.42 (m, 2H), 2.51–2.74 (m, 4H), 2.78–2.86 (m, 2H), 3.09 (d, 2H, J 6.1 Hz), 4.08 (t, 1H, J 6.1 Hz), 4.17 (s, 1H, CHFc), 4.04, 4.05, 4.15, 4.18 (s, 4C5H5), 3.63 (m, 1H), 3.74 (m, 2H), 3.78 (m, 1H), 3.82 (m, 1H), 3.87 (m, 1H), 3.96 (m, 2H), 4.22 (m, 2H), 4.26 (m, 1H), 4.30 (m, 1H), 4.36 (m, 2H), 4.44 (m, 1H), 4.49 (m, 1H, 4C5H4), 4.58 (d, 1H, CH2=, J 1.5 Hz), 5.06 (d, 1H, CH2=, J 1.5 Hz), 6.18 (s, 1H, CH=), 6.33 (s, 1H, CH=). 13C NMR (CDCl3) d: 28.18, 29.05, 31.57, 34.35, 36.68, 47.72, 47.83 (CH2), 52.26 (C), 65.32, 65.58 (CHFc), 68.47, 68.97, 69.19, 69.20 (4C5H5), 66.17, 66.58, 68.06, 68.19, 68.28, 68.31, 68.40, 68.53, 68.78, 69.09, 69.25, 69.42, 69.72, 70.01, 70.51, 72.49 (4C5H4), 83.06, 83.07, 83.92, 90.78 (CipsoFc), 109.52 (CH2=), 117.76, 121.51 (CH=), 128.32, 135.86, 136.01, 141.25, 159.47 (C).Found (%): C, 71.18; H, 5.99; Fe, 23.04. Calc. for C58H56Fe4 (%): C, 71.34; H, 5.78; Fe, 22.88.References 1 H. M. R. Hoffmann and H. V. Ernst, Chem. Ber., 1981, 114, 1182. 2 H. V. Ernst and H. M. R. Hoffmann, Angew. Chem., 1980, 92, 861. 3 R. J. Giguere, G. Ilsemann and H. M. R. Hoffmann, J. Org. Chem., 1982, 47, 4948. 4 P. G. Gassman and D. A. Singleton, J. Am. Chem. Soc., 1984, 106, 6085. 5 P. G. Gassman and D. A. Singleton, J. Am. Chem. Soc., 1984, 106, 7993. 6 W. R. Roush, H. R. Gillis and A. P. Essenfeld, J. Org. Chem., 1984, 49, 4674. 7 E. I. Klimova, A. N. Pushin and V. A. Sazonova, J. Organomet. Chem., 1984, 270, 319. 8 A. N. Pushin, E. I. Klimova and V. A. Sazonova, Zh. Obshch. Khim., 1987, 57, 1102 [J. Gen. Chem. USSR (Engl. Transl.), 1987, 57, 984]. 9 E. G. Perevalova, E. I. Klimova, V. V. Kryuchkova and A. N. Pushin, Zh.Obshch. Khim., 1989, 59, 873 [J. Gen. Chem. USSR (Engl. Transl.), 1989, 59, 770]. 10 E. I. Klimova, L. R. Ramirez, M. M. Garcia, N. N. Meleshonkova and A. M. Becerra, Dokl. Ross. Akad. Nauk, 1996, 351, 776 [Dokl. Chem. (Engl. Transl.), 1996, 351, 320]. 11 E. I. Klimova, L. R. Ramirez, M. M. Garcia and N. N. Meleshonkova, Izv. Akad. Nauk, Ser. Khim., 1996, 2743 (Russ. Chem. Bull., 1996, 45, 2602). 12 E. G. Perevalova, A. N. Pushin, E. I. Klimova, Yu. L. Slovokhotov and Yu. T. Struchkov, Metalloorg. Khim., 1989, 2, 1405 (Organomet. Chem. USSR, 1989, 2, 745). 13 V. N. Postnov, E. I. Klimova, M. M. Garcia and N. N. Meleshonkova, J. Organomet. Chem., 1994, 476, 189. 14 V. N. Postnov, E. I. Klimova, A. N. Pushin and N. N. Meleshonkova, Metalloorg. Khim., 1991, 4, 116 (Organomet. Chem., 1991, 4, 61). 15 V. N. Postnov, E. I. Klimova, N. N. Meleshonkova and M. M. Garcia, Dokl. Ross. Akad. Nauk, 1992, 326, 113 [Dokl. Chem. (Engl. Transl.), 1992, 326, 184]. 16 V. N. Postnov, E. I. Klimova, N. N. Meleshonkova and M. M. Garcia, J. Organomet. Chem., 1993, 453, 121. 17 M. J. A. Habib, J. Park and W. E. Watts, J. Chem. Soc. C, 1970, 2556. 18 W. E. Watts, J. Organomet. Chem., 1979, 17, 399. 19 M. Salisova, M. Puciova, V. N. Postnov and S. Toma, Chem. Papers, Chem. Zvesti, 1990, 44, 201. 3 DMA – H+ FcHC CH2 CHFc 14 DMA = C6H5NMe2 3 + 14 CHFc Me Fc Fc CHFc 15 15 Me Fc CHFc Fc Fc Me Fc CHFc Fc Fc 16a 16b Scheme 5 (a) (b) (c) Received: Moscow, 7th July 1998 Cambridge, 29th September 1998; Com. 8/05572F

ISSN:0959-9436     

出版商:RSC    

年代:1998

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) The first experimental detection, by OD ESR spectroscopy, of radical anions of siloles and germoles bearing hydrogen and chlorine substituents attached to the heteroatom Viktor A. Bagryansky,a Yuri N. Molin,*a Mikhail P. Egorovb and Oleg M. Nefedovb a Institute of Chemical Kinetics and Combustion, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russian Federation.Fax: +7 3832 34 2350; e-mail: molin@ns.kinetics.nsc.ru b N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow, Russian Federation. Fax: +7 095 135 5328 Short-lived radical anions of 2,3,4,5-tetraphenylsiloles and 2,3,4,5-tetraphenylgermoles have been detected for the first time by OD ESR spectroscopy. 1-Heterocyclopenta-2,4-dienes (metaloles), siloles and germoles, have become the subject of great interest from both synthetic and fundamental points of view.1 Special attention has been paid to the mono- and dianions of metaloles. Dianions of siloles and germoles were found to be aromatic heterocyclic systems.2 Information about the other negatively charged derivatives of metaloles, the radical anions, is still scarce.Dessy and Pohl3 have detected by ESR spectroscopy the formation of relatively stable paramagnetic intermediates upon partial reduction of 1,1,2,3,4,5-hexaphenylsilole and -germole. The unresolved ESR signals observed were tentatively assigned to the corresponding radical anions of metaloles. However, electrochemical reduction of these metaloles occurred via a two-electron irreversible process.3 The reduction of 1,1-dimethyl-2,3,4,5-tetraphenyl-1- silacyclopentadiene with potassium in 1,2-dimethoxyethane produced a stable blue solution which gave a well resolved ESR spectrum (approximately 60 lines).4 The authors assigned this spectrum to the silole radical anion without an analysis of the hyperfine structure of the ESR spectra of the paramagnetic species detected.Recently5 the electrochemical behaviour of different substituted 2,3,4,5-tetraphenylmetaloles (siloles, germoles and stannoles) was studied in MeCN solutions. All metaloles were found to reduce in a single one-electron irreversible step, indicating a very short lifetime (on the time scale of cyclic voltammetry) of the corresponding radical anions.However, using the method of quantum beats we were able to detect extremely short-lived (t ~ 10–100 ns) radical anions of 1,2,3,4-tetraphenylcyclopenta- 1,3-diene and 2,3,4,5-tetraphenyl-1-germacyclopenta-2,4-diene in decane solutions.6 Here we report on the detection of radical anions of 1,2,3,4-tetraphenylcyclopenta-1,3-diene 1 and its heteroanalogues, 2,3,4,5-tetraphenylsilole 2 and 2,3,4,5-tetraphenylgermoles 3–5, by the optically detected (OD) ESR technique.OD ESR spectra of spin-correlated radical ion pairs generated by X-ray irradiation were recorded with an X-band ER-200D Bruker spectrometer under stationary conditions described earlier.7 Data were accumulated in a lock-in amplifier SR-800 and processed on a computer.The microwave power applied to the cavity was 700 mW. Samples were degassed by a repeat freeze–pump–thaw procedure before the experiments. A chromatographically pure solvent squalane (99%, Fluka) was additionally purified on a column with an activated silica gel. Metaloles 2–5 were obtained according to known procedures.8–10 OD ESR spectra of paramagnetic species produced from the compounds 1–5 in squalane (10–3 M) at room temperature are E Ph Ph Ph Ph R' R'' 1 E = C, R' = R'' = H 2 E = Si, R' = R'' = H 3 E = Ge, R' = R'' = H 4 E = Ge, R' = R'' = Cl 5 E = Ge, R' = Me, R'' = Cl aFrom ref. 11. bCorresponds to 35Cl. Upon simulation the ratio of hfs constants for isotopes 35Cl and 37Cl was suggested to be equal to the ratio of their magnetic moments. Table 1 HFS constants and linewidth in the ESR spectra of radical anions of compounds 1–5.Compound X in EX2 fragment a(X)/G (OD ESR) a(X)/G (quantum beats)a DHpp/G 1 H, H 24.6 25.0 7.4 2 H, H 17.0 15.6 7.8 3 H, H 15.4 15.0 5.5 4 Cl, Cl 7.0b 7.0 5.5 5 Cl 12.4b 11.4 7.0 1 2 3 4 5 20 G Figure 1 OD ESR spectra of radical ion pairs generated by the X-ray irradiation of 10–3 M solutions of 1–5 in squalane at room temperature.Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) given in Figure 1. Simulation revealed the presence (when separated from the level of noise) of unresolved signals of ca. 20 G width along with the observed components of hyperfine structure. In the case of paramagnetic species from compounds 3 and 4 these unresolved signals are rather intense and have a width of ca. 10 G. This results in an increase in the intensity of the central component of the multiplets. We assigned the resolved components of the ESR spectra (Figure 1) to the radical anions of compounds 1–5. Indeed, the hyperfine splittings in these spectra correspond to the interaction of an unpaired electron with two equivalent hydrogen atoms (1–3; EH2 moieties; E = C, Si, Ge), two equivalent chlorine atoms (4; GeCl2 moiety), and one chlorine atom (5; GeClMe moiety) in the radical anions of 1–5.The corresponding hyperfine splitting (hfs) constants and line widths obtained by computer simulation are shown in Table 1. The counter ion of (1–5)·– in the radical ion pairs can be either radical cations (1–5)·+ or squalane holes which exhibit a wide unresolved spectrum.The following facts also confirm the correctness of our assignment of ESR spectra (Figure 1) to radical anions (1–5)·–. The value of the hfs constant a(H) for paramagnetic species generated from 1 is close to that reported12 for the radical anion (1)·– (25.3 G). Moreover, the hfs constants found in this work are close to those recently obtained by the analysis of the shape of quantum beats11 (see Table 1). It has been demonstrated11 that the quantum beats are caused by hyperfine interaction in the radical anions (1–5)·– rather than in the radical cations (1–5)·+. In the case of radical cations (1–5)·+ one could expect much smaller hfs constants. For example, a(H) constant corresponding to the interaction of an unpaired electron with a CH2 moiety in the cyclopentadiene radical cation is less than 2 G.13 The small value of a(CH2) in the cyclopentadiene radical cation can be explained within the framework of the Hückel approximation.The system of p-electrons in cyclopentadiene is similar to that in butadiene. In the butadiene radical ions an unpaired electron occupies the molecular orbital with contributions from the atomic orbitals of edged atoms of the same sign in the radical anion and of the opposite sign in the radical cation.This means that in the cyclopentadiene radical cation the protons of the CH2 moiety are situated in the nodal plane which results in a weak hyperfine interaction with these atoms. A decrease in temperature (to –25 °C) does not change the pattern of the spectra, but instead causes line broadening up to 2–3 G and an increase in the signal to noise ratio.In the case of radical anion (4)·–, the hyperfine structure disappears almost completely at –25 °C. Radical anions (4)·– and (5)·– are the first radical anions of group 14 organoelement halides to be detected in solution. The formation of radical anions of R3EHal (E = Si, Ge) during the electrochemical reduction of R3EHal was suggested,14 but the most accepted point of view is that the electrochemical reduction occurs via dissociative attachment of an electron.15 However, it was shown recently by electron-transmission and dissociative attachment spectroscopies that the replacement of the central carbon atom in compounds Me3EX (E = C, Si Ge, Sn; X = Cl, Br) with a heavier group element led to a dramatic reduction of the halogen anion yield indicating the stabilization of the corresponding radical anions.16 In fact, radical anions of halosilanes17 and halogermanes18 were detected by ESR spectroscopy only in low temperature matrices.This work was financially supported by the Russian Foundation for Basic Research (grant nos. 96-03-33694 and 96-03-32836) and by the Russian Ministry of Education (grant no. 3H-218-98 in the Field of Fundamental Research). References 1 J. Dubac, A. Laporterie and G. Manuel, Chem. Rev., 1990, 90, 215. 2 B. Goldfuss and P. von R. Schleyer, Organometallics, 1997, 16, 1543 and references therein. 3 R. E. Dessy and R. L. Pohl, J. Am. Chem. Soc., 1968, 90, 1995. 4 E. G. Janzen, J. B.Pickett and W. H. Atwell, J. Organomet. Chem., 1967, 10, 6. 5 (a) K. S. Nosov, M. P. Egorov, R. D. Rakhimov, A. A. Moiseeva and K. P. Butin, Abstracts of Papers, VIth International Conference on Chemistry of Carbenes and Related Species, St. Petersburg, 1998, p. 127; (b) K. S. Nosov, PhD Thesis, Moscow, N. D. Zelinsky Institute of Organic Chemistry, 1997. 6 V. A. Bagryansky, V.I. Borovkov, Yu. N. Molin, M. P. Egorov and O. M. Nefedov, Mendeleev Commun., 1997, 132. 7 Yu. N. Molin, O. A. Anisimov, V. I. Melekhov and S. N. Smirnov, Faraday Discuss. Chem. Soc., 1984, 78, 289. 8 R. Muller, Z. Chem., 1968, 262. 9 M. D. Curtis, J. Am. Chem. Soc., 1967, 89, 4241. 10 M. D. Curtis, J. Am. Chem. Soc., 1969, 91, 6011. 11 V. A. Bagryansky, V. I. Borovkov, Yu. N. Molin, M. P. Egorov and O. M. Nefedov, Chem. Phys. Lett., 1998, 295, 230. 12 B. J. Tabner and T. Walker, J. Chem. Soc., Perkin Trans. 2, 1975, 1304. 13 T. Shida, Y. Egava, H. Kubodera and T. Kato, J. Chem. Phys., 1980, 73, 5963. 14 R. J. P. Corriu, G. Dabosi and M. Martineau, J. Organomet. Chem., 1980, 188, 63. 15 V. V. Zhuikov, Usp. Khim., 1997, 66, 564 (Russ. Chem. Rev., 1997, 66, 509). 16 A. Modelli, F. Scagnolari, G. Distefado, M. Guerra and D. Jones, Chem. Phys., 1990, 145, 89. 17 S. Uchimura, A. Hasegawa and M. Hayashi, Mol. Phys., 1979, 38, 413. 18 A. Hasegawa, S. Uchimura and M. Hayashi, Mol. Phys., 1980, 40, 697. Received: Moscow, 5th October 1998 Cambridge, 5th November 1998; Com. 8/07926I

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Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) An efficient synthesis of hydroxyfurazans Aleksei B. Sheremetev* and Natalya S. Aleksandrova N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow, Russian Federation. Fax: +7 095 135 5328; e-mail: sab@cacr.ioc.ac.ru The nitro group on the furazan ring is found to undergo a facile regioselective displacement by a hydroxy group on treatment with the solid crystal hydrate of inorganic bases in dry acetonitrile; this straightforward reaction affords the hydroxyfurazans in high yields.In connection with a project directed at the investigation of the nucleophilic reactions of nitrofurazans 1,1,2 we have studied the reactivity of 1 with solid anhydrous bases in dry conditions resulting in ether bond formation and giving difurazanyl ether derivatives 2 (Scheme 1).3–6 The yields of 2 were generally very good.A major limitation of this method is that the reaction is successful only with highly electron-withdrawing groups (R). This unusual reaction pathway was identified, and a mechanism for the transformation proposed.3 We now report the surprising finding that a similar reaction between certain nitrofurazans 1 and the solid crystal hydrate of inorganic bases in dry acetonitrile can be used to synthesize hydroxyfurazan 3† in high yield, with no significant difurazanyl ether derivatives (Scheme 2).When nitrofurazan 1a–d (0.01 mol) was stirred with a suspension of the crystal hydrate (0.01–0.02 mol) in MeCN (15 ml), the reaction was completed as a rule in less than 2 h at 75–80 °C, and the corresponding hydroxyfurazan 3a–d emerged as the only reaction product.The results obtained are summarised in Table 1. On the other hand, the inclusion of 3% water in the MeCN reaction medium halved the yields of the hydroxyfurazans. This set of by-products was observed under the experimental conditions.It should be noted that low yields of hydroxyfurazans previously obtained from the corresponding nitrofurazans and aqueous alkali in organic solvents were also dependent on by-product formation.6,7 For example, reaction between 3,4-dinitrofurazan 1a and aqueous alkali in acetone proceeded via nonselective attack at each carbon to produce a mixture of mono and dihydroxy derivatives.† The compounds 3a,3,7 3c,6,7 3d7 and 3e3,7 corresponded in all respects with the compounds described earlier. New compounds gave satisfactory combustion analyses and accurate mass measurements. Some selected data for 3b: mp 107–108 °C; 13C NMR ([2H6]acetone) d: 149.8 (C-3), 152.4 (C-2), 157.0 (C-4, C–NO2), 158.4 (C-1, C–OH); 14N NMR ([2H6]acetone) d: –36.3 (NO2, Dn1/2 = 10 Hz), –60.8 (N2O, Dn1/2 = 40 Hz); IR, (n/cm–1): 3120–2790, 1580, 1495, 1425, 1345, 1245, 1180, 1120, 1090, 1020, 925; MS, m/z: 185 (M+ – N2 – NO).For 3f: mp 158–159 °C; IR, (n/cm–1): 3080–2850, 1630, 1575, 1400, 1300, 1265–1175, 1073, 1055, 1000, 910; MS, m/z: 168 (M+), 140 (M+ – N2), 110 (M+ – N2 – NO). The selectivity observed in the reaction is most likely a consequence of the incorporation of the intermediate hydroxyfurazan salt into the crystal lattice of the starting crystal hydrate, which prevents them from further transformation.In conclusion, a novel, simple and efficient method for the synthesis of hydroxyfurazans has been developed. Hydroxyfurazans with such reactive groups as nitro, cyano and azoxy are now readily accessible. The authors thank the International Science Foundation (grant nos.MM9000 and MM9300) and the Russian Foundation for Basic Research (grant no. 98-03-33024a) for financial support of this work. References 1 (a) A. B. Sheremetev, E. V. Mantseva, N. S. Aleksandrova, V. S. Kuzmin and L. I. Khmel’nitskii, Mendeleev Commun., 1995, 25; (b) for a recent review which cites several other earlier papers that deal with the reactivity of nitrofurazans, see: A.B. Sheremetev, Ross. Khim. Zh. (Zh. Ross. Khim. Ob-va im. D. I. Mendeleeva), 1997, 41 (2), 43 (in Russian). 2 A. B. Sheremetev and E. V. Shatunova, Proceedings of the 28th International Annual ICT-Conference, Combustion and Detonation, Karlsruhe, 1997, 94/1-8. 3 A. B. Sheremetev, O. V. Kharitonova, T. M. Melnikova, T. S. Novikova, V.S. Kuzmin and L. I. Khmel’nitskii, Mendeleev Commun., 1996, 141. 4 A. B. Sheremetev, V. O. Kulagina and E. A. Ivanova, J. Org. Chem., 1996, 61, 1510. 5 A. B. Sheremetev, S. E. Semenov, V. S. Kuzmin, Yu. A. Strelenko and S. L. Ioffe, Chemistry-European Journal, 1998, 4 (6), 1023. N O N R NO2 B N O N R O N O N R 1 2 Scheme 1 Reagents and conditions: MeCN, 80 °C, B = MX or M2Y (M = Li, Na, K; X = NO2, OAc, CN, HCO3; Y = CO3, HPO4).N O N R NO2 B·nH2O N O N R 1a–d 3a–d OH Scheme 2 Reagents and conditions: MeCN, 75–80 °C. Table 1 Reaction of 3-R-4-nitrofurazan with the solid crystal hydrate of inorganic bases B·nH2O in dry acetonitrile. Entry R B·nH2O Reaction time/min Yield (%) 1 NO2 Na2CO3·10H2O 45 3a, 98 2 Na2B2O7·10H2O 60 3a, 86 3 Na2CO3·10H2O 10 3b, 57 4 Na2CO3·10H2O 25 3c, 70 5 NaOAc·3H2O 35 3d, 87 6 CN Na2CO3·10H2O 60 3e, 91 7 NaOAc·3H2O 200 3e, 93 8 Ba(OH)2·8H2O 65 3f, 79 9 CsF·1.5H2O 120 3f, 73 N O N O2N N N O 4 3 N O N O2 N N N N N N N O N NN N N MeMendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) 6 A. B. Sheremetev, V. O. Kulagina, N. S. Aleksandrova, D. E. Dmitriev, Yu. A. Strelenko, V. P. Lebedev and Yu. N. Matyushin, Propellants, Explosives, Pyrotechnics, 1998, 23 (3), 142. 7 A. B. Sheremetev, O. V. Kharitonova, E. V. Nesterova, V. O. Kulagina, E. V. Shatunova, N. S. Aleksandrova, T. M. Melnikova, E. A. Ivanova, D. E. Dmitriev, V. A. Eman, V. S. Kuzmin, T. S. Novikova and O. V. Lebedev, Zh. Org. Khim., 1998, in press. Received: Moscow, 9th September 1998 Cambridge, 8th October 1998; Com. 8/07857B

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Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) Electrooxidative rearrangement of 5,(n + 6)-dimethoxy-1-oxabicyclo[n.4.0]alkanes (n = 4, 10) into -(2-methoxytetrahydrofur-2-yl)alkanoic esters Yuri N. Ogibin,* Alexander O. Terent’ev, Alexey I. Ilovaisky and Gennady I. Nikishin N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow, Russian Federation.Fax: +7 095 135 5328 5,(n + 6)-Dimethoxy-1-oxabicyclo[n.4.0]alkanes undergo a previously unknown oxidative rearrangement into w-(2-methoxytetrahydrofur- 2-yl)alkanoic esters during electrolysis in methanol. Rearrangement of 5,(n + 6)-dimethoxy-1-oxabicyclo[n.4.0]alkanes 1a,b† into w-(2-methoxytetrahydrofur-2-yl)alkanoic esters 2a,b occurred when compounds 1a,b were electrolysed in methanol in the presence of Bu4NBF4 as an electrolyte, in an undivided cell with a platinum anode and a stainless steel cathode, at room temperature with the passage of 7 F mol–1 of electric current.Products 2a,b were formed in yields of 65– 75% (Scheme 1).‡ The structures of products 2a,b were assigned based on their spectral data.§ Thus, there were signals (dH 1.76–2.13, 3.14, 3.85 and dC 47.5–47.8, 66.9–67.1, 108.8–109.1) common to the protons and 13C-nuclei of the 2-methoxytetrahydrofuryl group.7 In addition, their structures were confirmed by acidic hydrolysis into a mixture of tautomers: methyl w-hydroxy-(2-methoxytetrahydrofur- 2-yl)alkanoates (3'a,b) (minor) and w-hydroxy- (w-3)-oxoalkanoates (3''a,b) (major).‡ Evidence for the fact that the hydrolysis products constitute a tautomer mixture is provided by an infrared absorption characteristic of the ketone and ester carbonyl groups (1715 and 1735 cm–1) and 20 lines in the 13C NMR spectrum of 3a.The electrochemical transformation of compound 1a into ester 2a seems to result from a transannular rearrangement of the cationic intermediate 4a into a more stable carbocation 6a via the oxonium ion 5a and subsequent conversion of 6a into 2a (Scheme 2).¶ In a similar manner ester 2b is formed from compound 2a.Judging by the absence of orthoesters among the electrolysis products,†† the formation of which might be expected as a result of solvolysis of the cationic intermediates 4, the reaction either † The starting compounds 1a,b were obtained from 1-oxabicyclo[4.4.0]dec- 5(10)-ene1 and 1-oxabicyclo[10.4.0]hexadec-5(16)-ene2 in 65% yield under the conditions used for the electrochemical dimethoxylation of linear and monocyclic enol ethers.3–5 ‡ Electrolysis of 1 (typical procedure).An electrolyte solution (9 mmol), compound 1 (5 mmol) and n-decane (internal standard, 3 mmol) in MeOH (15–25 ml) were placed in an undivided cell described previously6 and then electrolysed at a constant current (0.5 A) and room temperature with efficient stirring until more than 90% conversion of 1 (2.5 h, 7 F mol–1) had occurred.The solvent was then removed, the residue extracted with hexane (2×20 ml), the combined extracts were concentrated and the products isolated using vacuum distillation or flash chromatography with hexane–ethyl acetate (1%) as eluent.does not proceed at all, or occurs substantially more slowly than the rearrangement of intermediates 4 into 6. § Spectral data for 2a: 1H NMR (200 MHz, CDCl3) d: 1.20–1.75 (m, 6H, CH2 of aliphatic chain), 1.76–2.13 (m, 4H, CH2 of THF ring), 2.31 (t, 2H, CH2COO), 3.14 (s, 3H, MeO), 3.64 (s, 3H, COOMe), 3.85 (t, 2H, CH2O). 13C NMR (50 MHz, CDCl3) d: 173.8 (COO), 109.1 (O–C–O), 67.1 (CH2O), 51.3, 47.8 (MeO), 35.7, 35.2, 33.8, 24.97, 24.14, 24.07 (CH2).IR (thin film, n/cm–1): 1060, 1165 (C–O), 1735 (C=O). For 2b: 1H NMR (200 MHz, CDCl3) d: 1.20–1.75 (m, 18H, CH2 of aliphatic chain), 1.76–2.13 (m, 4H, CH2 of THF ring), 2.31 (t, 2H, CH2COO), 3.17 (s, 3H, MeO), 3.67 (s, 3H, COOMe), 3.85 (t, 2H, CH2O). 13C NMR (50 MHz, CDCl3) d: 173.5 (COO), 108.8 (O–C–O), 66.9 (CH2O), 51.0, 47.5 (MeO), 34.0, 29.07, 28.95, 26.25, 24.67, 24.10, 23.85, 23.61 (CH2). IR (thin film, n/cm–1): 1070, 1175 (C–O), 1735 (C=O).For 3a: 1H NMR (250 MHz, CDCl3) d: 1.55–1.90 (m, 4H, CH2), 2.10–2.23 (m, 2H, CH2COO), 2.30–2.63 (m, 4H, CH2C=O), 3.35 (t, 2H, CH2OH), 3.68 (s, 3H, MeO), 4.28 (t, 2H, CH2O of THF ring). 13C NMR (50 MHz, CDCl3) d: 210.1 (C=O), 174.2, 173.8 (O=C–O), 104.4 (O–C–O), 66.9, 61.8 (CH2), 51.8, 51.3 (OMe), 43.8, 41,8, 33.92, 32.63, 32.31, 31.30, 30.62, 26.32, 25.70, 25.45, 23.80, 22.67 (CH2).IR (CCl4, n/cm–1): 1060, 1165 (C–O), 1715, 1735(C=O), 3660 (OH). For 3b: 1H NMR (200 MHz, CDCl3) d: 1.27 (br. s, 12H, CH2), 1.50– 2.00 (m, 6H, CH2), 2.30 (t, 2H, CH2COO), 2.43 and 2.56 (t, 4H, CH2COCH2), 3.65 (t, 2H, CH2OH), 3.67 (s, 3H, OMe), 4.87 (br.s, 1H, OH). 13C NMR (50 MHz, CDCl3) d: 211.9 (C=O), 174.3 (COO), 62.3 (CH2OH), 51.4 (OMe), 42.9, 39.5, 34.05, 29.29, 29.14, 27.90, 26.43, 24.88, 23.81 (CH2). IR (CCl4, n/cm–1): 1060, 1165 (C–O), 1715, 1735(C=O), 3660 (OH). ¶ Similar involvement of the tetrahydrofuranyl oxonium ions in the transformation of linear methoxy-substituted aliphatic carbenium ions was discussed in detail in ref. 8. ††Tests for the content of orthoesters in the electrolysis products were performed using the procedure described in ref. 9. w O (CH2)n OMe OMe 1 2 3 4 5 n + 6 1a,b a n = 4 b n = 10 i O COOMe OMe n 2a,b ii O COOMe OH n 3'a,b HO COOMe O n 3''a,b Scheme 1 Reagents and conditions: i, Bu4NBF4, MeOH, 20 °C, 2.5 h (7 F mol–1); ii, 10% HCl, 20 °C, 20 min.O (CH2)4 OMe OMe 1a – e O MeO MeO OMe 4a O MeO MeO OMe 5a O MeO MeO OMe 6a 2a i, MeOH/–H+ ii, –e Scheme 2 MeOH O (CH2)n 4 OMe MeO OMe MeO MeOH – H+ 7Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) The rearrangement of 1 into 2 is accompanied by the side process of solvent oxidation and this leads to an increase in the consumption of electricity (7 F mol–1) with respect to the theoretical amount (2 F mol–1) in order to achieve a high degree of conversion of 1.In conclusion, it may be noted that the transformation of 5,(n + 6)-dimethoxy-1-oxabicyclo[n.4.0]alkanes 1a,b into w- methoxy-w-(tetrahydrofur-2-yl)alkanoic 2a,b and w-hydroxy- (w-3)-oxoalkanoic 3a,b esters is a new synthetic approach to substituted alkanoic esters of a similar type, which may find application in, e.g.the preparation of w-(4-oxobutanoyl)alkanoic esters and 2-(w-alkoxycarbonylalkyl)cyclopent-2-en-1-ones,10 synthons for the synthesis of prostaglandins, pheromones and other valuable organic products. This work was financially supported by the Russian Foundation for Basic Research (grant no. 97-03-33159). References 1 I. J. Borowitz, G. Gonis, R. Kelsey, R. Rapp and G. J. Williams, J. Org. Chem., 1966, 31, 3032. 2 (a) J. Becker and G. Ohlaff, Helv. Chim. Acta, 1971, 54, 2889; (b) I. J. Borowitz, V. Bandurco, M. Neyman, R. D. G. Rigby and S. Ueng, J. Org. Chem., 1973, 38, 1234; (c) J. R. Mahayan and H. C. de Araujo, Synthesis, 1980, 64; (d) L. I. Zakharkin, A. P. Praynishnikov and V.V. Guseva, Zh. Org. Khim., 1979, 15, 1441 [J. Org. Chem. USSR (Engl. Transl.), 1979, 15, 1285]; (e) L. I. Zakharkin and I. M. Churikova, Izv. Akad. Nauk, Ser. Khim., 1994, 659 (Russ. Chem. Bull., 1994, 43, 608). 3 (a) T. Shono, Y. Matsumura and Y. Nakagawa, J. Am. Chem. Soc., 1974, 96, 3532; (b) T. Shono, M. Okawa and I. Nishiguchi, J. Am. Chem. Soc., 1975, 97, 6144; (c) T.Shono, I. Nishiguchi and M. Nitta, Chem. Lett., 1976, 1319; (d) T. Shono, Y. Matsumura, H. Hamaguchi, T. Imanishi and K. Yoshida, Bull. Chem. Soc. Jpn., 1978, 51, 2179; (e) T. Shono, I. Nishiguchi, S. Koshimura and M. Okawa, Bull. Chem. Soc. Jpn., 1978, 51, 2181. 4 S. Torii, T. Inokuchi and R. Oi, J. Org. Chem., 1982, 47, 47. 5 B. Belleau and V. K. Au-Young, Can. J. Chem., 1969, 47, 2117. 6 Yu. N. Ogibin, A. I. Ilovaisky and G. I. Nikishin, Izv. Akad. Nauk, Ser. Khim., 1994, 1624 (Russ. Chem. Bull., 1994, 43, 1536). 7 T. Shono, Y. Matsumura, O. Onomura and Y. Yamada, Synthesis, 1987, 1099. 8 E. L. Allred and S. Winstein, J. Am. Chem. Soc., 1967, 89, 3991, 4012. 9 Methoden der Organischen Chemie (Houben-Weyl), 4th edn., Georg Thieme Verlag, Stuttgart, 1965, Band VI/3, S. 315. 10 (a) E. Wenkert, B. L. Buckwalter, A. A. Graveiro, E. L. Sanchez and S. S. Sathe, J. Am. Chem. Soc., 1978, 100, 1267; (b) J. M. Reuter and R. G. Salomon, J. Org. Chem., 1978, 43, 4247; (c) U. Valcavi, P. Farina, S. Innocenti and V. Simoni, Synthesis, 1983, 124; (d) C. Boga, D. Savoia, C. Trombini and A. Umani-Ronchi, Synthesis, 1986, 212; (e) D. Savoia, C. Trombini and A. Umani-Ronchi, J. Org. Chem., 1982, 47, 564; (f) H. Stach and M. Hesse, Helv. Chim. Acta, 1987, 70, 315; (g) N. W. A. Geraghty and N. M. Morris, Synthesis, 1989, 603; (h) Yu. N. Ogibin, E. K. Starostin, A. V. Aleksandrov, K. K. Pivnitsky and G. I. Nikishin, Synthesis, 1994, 901. Received: Moscow, 10th August 1998 Cambridge, 11th September 1998; Com. 8/06555A

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Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) 2-Diazoacethydrazide derivatives and their ring-chain transformations Yury A. Rosin,a Elena A. Vorob’eva,a Yury Yu. Morzherin,a Alexander C. Yakimov,a Wim Dehaenb and Vasiliy A. Bakulev*a a Urals State Technical University, 620002 Ekaterinburg, Russian Federation. Fax: +7 3432 74 5483; e-mail: crocus@htf.ustu.ru b Laboratory of Organic Synthesis, Department of Chemistry, B-3001 Heverlee (Leuven), Belgium 1-Amino-1,2,3-triazol-5-olates 6, 13 and 14 have been obtained by the introduction of a diazo group into N-benzylidene-protected hydrazides of cyanoacetic and malonic acids.These compounds form open-chain isomers of 1-amino-5-hydroxy-1,2,3-triazoles upon acidification with an aqueous solution of HCl.Compounds 8, 15 and 16 are the first examples of the group of a-diazoacethydrazides. a-Diazoacetamides and the products of their cyclisation, 5-hydroxy-1,2,3-triazoles, have been extensively studied,1,2 though until this report, the relevant literature has carried no examples of diazo compounds containing the hydrazide group in the a-position. This paper presents data on the synthesis of the first examples of 2-diazoacethydrazides and derivatives of their cyclic isomers, 1-amino-1,2,3-triazoles.We showed previously3 that the interaction of 2-amino- 2-cyanoacethydrazide 1 with sodium nitrite in an aqueous solution of hydrochloric acid (or with alkyl nitrites in glacial acetic acid) proceeds simultaneously at the amino and hydrazide groups with the formation of 2-diazo-2-cyanoacetazide. To carry out the reaction selectively at the amino group, we protected of the hydrazide group with N-benzylidene.Interaction of hydrazide 1 with benzaldehyde leads to smooth formation of hydrazone 2. Reaction of 2 with butyl nitrite in glacial acetic acid yields N-benzylidene-2-diazo-2-cyanoacethydrazide 3. We found that this compound was unstable in organic solvents and underwent slow cyclisation to 1-benzylideneamino- 5-hydroxy-1,2,3-triazole-4-carbonitrile 4.The 13C NMR spectrum correlates with the cyclic structure of 4: it contains signals at 101.8 and 153.4 ppm, corresponding to the 4-C and 5-C atoms of 5-hydroxytriazoles.4 As in the case of diazomalonamides,5 cyclisation of compound 3 is accelerated by the addition of bases, and the use of sodium ethylate leads to the formation of sodium 1-benzylideneamino- 4-cyano-1,2,3-triazol-5-olate 5.The interaction of 5 with hydrazine results in the removal of benzylidene protection and formation of sodium 1-amino-5-cyano-1,2,3-triazol-5-olate 6. Upon addition of HCl (1 mol) to an aqueous solution of compound 6, 2-cyano-2-diazoacethydrazide 8 is formed as a result of ring opening in a presumed intermediate, 1-amino- 5-hydroxy-1,2,3-triazole-4-carbonitrile 7. Thus, we have synthesised the first example of 2-diazomalonohydrazides.To synthesise 2-ethoxycarbonyl and 2-methylcarbamoyl derivatives of 2-diazoacethydrazide, we studied the interaction of hydrazones of 2-ethoxycarbonyl- and 2-methylcarbamoylacethydrazides 9 and 10 with tosyl azide in the presence of sodium ethylate (‘diazo group transfer’ reaction).6 This reaction was found to result in the formation of sodium salts of 5-hydroxytriazoles 11 and 12, but not of the expected 2-diazomalonohydrazones.It is noteworthy that one could expect formation of two isomeric triazoles 12 and 17 in the reaction of methylcarbamoyl derivatives 10 with TsN3 via cyclisation of the intermediate diazo compounds at the amide or hydrazide groups.It was found that this reaction yields only isomers 12; i.e., only heterocyclisation with the participation of diazo and hydrazide fragments is realised. Treatment of 1-benzylideneamino-1,2,3- triazoles 11 and 12 with hydrazine leads to high yields of 1-amino-1,2,3-triazol-5-olates 13 and 14.As in the case of compound 6, diazohydrazides 15 and 16, which are chain isomers of 5-hydroxy-1,2,3-triazoles, are formed in the reaction of sodium salts 13 and 14 with hydrochloric acid. Thus, we have synthesised the first examples of 2-diazoacethydrazides 8, 15 and 16, and the products of their cyclisation: derivatives of 1-amino-5-hydroxy-1,2,3-triazoles 4–6 and 11– 14.† All new compounds have satisfactory elemental analyses, IR and NMR spectroscopic data.This work was supported by the Russian Foundation for Basic Research (grant no. 98-03-33045a). NH2 NC NHNH2 O NH2 NC N O N Ph H i ii N2 NC N O N Ph H iii N N N N Ph NC OY 1 2 3 4 Y = H 5 Y = Na EtONa 5 iv N N N NH2 NC OY 6 Y = Na 7 Y = H v 7 N2 NC NHNH2 O 8 Scheme 1 Reagents and conditions: i, PhCHO, EtOH, 20 °C; ii, ButONO, AcOH, 10 °C; iii, 20 °C, 24 h in DMSO or CHCl3; iv, H2NNH2, EtOH, 78 °C, 12 h; v, HCl, H2O, 0–10 °C.X N N Ph O O H i N N N N Ph O X ONa ii N N N NH2 O X ONa HCl X N NH2 O O H N2 N N N Me NaO O NH N Ph 9,10 11,12 13,14 15,16 17 9,11,13,15 X = EtO 10,12,14,16 X = MeNH Scheme 2 Reagents and conditions: i, TsN3, EtOH, EtONa; ii, EtOH, H2NNH2, 78 °C.Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) References 1 H. Wamhoff, in Comprehensive Heterocyclic Chemistry, eds. A. R. Katritzky and C. W. Rees, Pergamon Press, Oxford, 1984, vol. 5, ch. 4.11, p. 350. † The 1H and 13C NMR spectra were recorded in [2H6]DMSO solution with a Bruker WH-250 spectrometer at 250 MHz, and the IR spectra were recorded in KBr using a UR-20 spectrometer. Synthesis of 3 and 4.A solution of amine 2 (4 g, 0.02 mol) in 12 ml of glacial acetic acid at 10–15 °C was treated with butyl nitrite (2.65 g, 0.025 mol). After stirring for 1 h, the precipitate 3 was filtered off. Recrystallisation of 3 from MeCN gives triazole 4. Yield 2.22 g (52%), mp 162–164 °C (CAUTION! Explosive). 1HNMR d: 9.31 (s, 1H, N=CH), 12.31 (s, 1H, OH).Synthesis of 5. Compound 5 was obtained by treatment of 4 with an equimolar quantity of sodium ethylate in absolute ethanol with subsequent precipitation from diethyl ether. Yield 91%, mp 322–324 °C. 1H NMR d: 9.32 (s, 1H, N=CH). Synthesis of 11 and 12 was performed by a ‘diazo group transfer’ method.6 For 11: yield 72%, mp 225 °C (from EtOH, decomp.). 1H NMR d: 9.29 (s, 1H, N=CH), 4.15 (m, 2H, OCH2, J 6.9 Hz), 1.25 (m, 3H, Me, J 6.9 Hz).For 12: yield 93.7%, mp 240–245 °C (decomp.). 1H NMR d: 9.33 (s, 1H, N=CH), 7.89 (m, 1H, NH, J 4.8 Hz), 2.75 (d, 3H, NMe, J 4.8 Hz). General method for the preparation of 6, 13 and 14. Compounds 5, 11 or 12, respectively (2 mmol) were mixed with dry ethanol (8 ml) and hydrazine (100%, 2 mmol) and refluxed for 12 h. The product was filtered and washed with ethanol.For 6: yield 46%, mp 285 °C (decomp.). For 13: yield 65%, mp 170–200°C (decomp.). 1H NMR d: 5.25 (br. s, 2H, NH2), 4.13 (q, 2H, CH2, J 7.0 Hz), 1.23 (t, 3H, J 7.0 Hz). For 14: yield 90%, mp 300–305 °C. 1H NMR d: 7.86 (q, 1H, CONH, J 4.6 Hz), 5.30 (s, 2H, NH2), 2.72 (d, 3H, Me, J 4.6 Hz). General method for the preparation of 8, 15 and 16.An aqueous solution of 6, 13 or 14 was mixed with 1 equiv. of HCl. After evaporation of 8 and 15 solutions in vacuo to dryness the residue was extracted with ethanol. The product 16 was separated by filtration. For 8: yield 50%, mp 140 °C (decomp.). IR (n/cm–1): 2150 (N2), 2250 (CN). For 15: yield 55%, mp 157–160 °C. 1H NMR d: 9.94 (br. s, 1H, NH), 5.5–7.5 (br. s, 2H, NH2) 4.28 and 4.23 (2q, 2H, CH2, J 7.2 Hz), 1.27 (t, 3H, Me, J 7.2 Hz).IR (n/cm–1): 2145 (N2). For 16: yield 47%, mp 200–203 °C (decomp.). 1H NMR d: 7.87 (br. s, 1H, NH), 4.25 (br. s, 2H, NH2), 2.75 (d, 3H, Me, J 4.0 Hz). IR (n/cm–1): 2115 (N2). 2 V. A. Bakulev, C. O. Kappe and A. Pavda, in Organic Synthesis: Theory and Applications, JAI Press Inc., Greenwich, London, 1996, vol. 3, pp. 149–229. 3 M. Yu. Kolobov, V. A. Bakulev, V. C. Mokrushin and A. T. Lebedev, Khim. Geterotsikl. Soedin., 1987, 1503 [Chem. Heterocycl. Compd. (Engl. Transl.), 1987, 1202]. 4 G. L’Abbe, P. Delbeke, G. V. Essche, I. Luyten, K. Vercautern and S. Toppet, Bull. Soc. Chim. Belg., 1990, 90, 1007. 5 V. A. Bakulev, Yu. Yu. Morzherin, A. T. Lebedev, E. F. Dankova, M. Yu. Kolobov and Yu. M. Shafran, Bull. Soc. Chim. Belg., 1993, 102, 493. 6 M.Regitz, Diazoalkane: Eigenschaften und Synthesen, Thieme, Stuttgart, 1977, p. 45 (in German). Received: Moscow, 4th August 1998 Cambridge, 10th September 1998; Com. 8/06231E

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年代:1998

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Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) Reaction of aromatic isocyanides with triethylamine: a new method for the synthesis of indole betaines Maxim A. Mironov* and Vladimir S. Mokrushin Department of Technology of Organic Synthesis, Urals State Technical University, 620002 Ekaterinburg, Russian Federation. Fax: +7 3432 74 5483; e-mail: crocus@htf.ustu.ru A new reaction between aromatic isocyanides containing electron-withdrawing substituents and triethylamine is described which allows 2-triethylammonium-3-arylaminoindolates to be obtained.The structure of the compounds was determined by X-ray analysis, NMR and mass spectroscopy. The indole structure is central to a great number of biologically active compounds. Various cyclisations of aromatic isocyanides are convenient methods for the synthesis of indole derivatives. For example, dianyl indigo is a major product of oligomerisation of phenyl isocyanide.1 The interaction of aryl and naphthyl isocyanides with ketones in the presence of an acid catalyst leads to anilides of 3H-indolecarboxylic-2-acid.2 The intramolecular cyclisation of 2-alkylphenyl isocyanides is a convenient method for the preparation of 3-alkylindoles.3 We have found that refluxing of 3,5-bis(trifluoromethyl)- phenyl isocyanide 1a in hexane with triethylamine results in the formation of 2-triethylammonium-3-(3',5'-bistrifluoromethyl)- phenylamino-4,6-bistrifluoromethylindolate 2a in 85% yield (Scheme 1),† in contrast to the methods described in the literature dealing with the synthesis of indole derivatives from isocyanides.1–3 The 1H NMR spectrum of the compound exhibited resonance signals of two non-equivalent aromatic rings at d 6.3–8.1 ppm, a triplet of three methyl groups at d 1.05 ppm and two multiplets of three methylene groups at d 3.6–4.1 ppm.The mass spectrum of compound 2a exhibits a molecular ion peak m/z 579 [M]+ corresponding to the dimeric composition of the starting isocyanide plus a fragment of triethylamine.The main fragmentation ions are [M – 29]+ and [M – 86]+. These data suggest that indolate 2a results from the reaction of isocyanide 1a with triethylamine. However, 1H NMR and mass spectral data proved to be insufficient to provide unequivocal evidence of the structure of this unexpected product.An X-ray crystallographic analysis of compound 2a was therefore performed.‡ Two crystallographic molecules (A and B) in the compound 2a feature similar structures. The dihedral angle between the planes of the indole group and the phenyl ring [C(11)–C(16)] turned out to be 80.1° and 87.1° in molecules A and B, respectively. Most of the geometric parameters of molecules A and B are of standard nature,4 but the high value of the anisotropic temperature factor of the fluorine atoms can be assigned to the various positions of the trifluoromethyl groups.The reaction of aromatic isocyanides, bearing electron-withdrawing substituents (2-bromo-4-nitro 1b, 3-trifluoromethyl- 4-chloro 1c and 3,4,5-trichlorophenyl isocyanide 1d) with triethylamine proceeds similarly leading to the corresponding 2-triethylammonium-3-arylaminoindolates 2b–d. 1H NMR and mass spectral data for compounds 2b–d are similar to those for compound 2a. Phenyl isocyanide and 4-bromophenyl isocyanide do not interact with triethylamine under these conditions. The starting isocyanides 1a–d were obtained according to a well-known method.5 F(11) F(10) F(12) F(1) F(2) F(3) F(8) F(9) F(4) F(5) F(6) C(1) C(2) C(3) C(4) C(5) C(6) C(7) N(1) N(2) N(3) Figure 1 The crystal structure of 2a.The numeration of atoms does not correspond to IUPAC nomenclature. Selected bond lengths (Å): N(1)–C(1) 1.35(1), N(l)–C(4) 1.37(1), N(2)–C(2) 1.42(9), N(2)–C(11) 1.40(1), N(3)–C(1) 1.50(1), C(1)–C(2) 1.38(1), C(2)–C(3) 1.43(1), C(3)–C(4) 1.43(1), C(3)–C(8) 1.40(1), C(4)–C(5) 1.39(1), C(5)–C(6) 1.37(1), C(6)–C(7) 1.41(1), C(7)–C(8) 1.39(1); selected bond angles (°): C(1)–N(1)–C(4) 102.8(6), C(2)–N(2)–C(11) 121.0(6), N(1)–C(1)–N(3) 117.6(6), N(1)–C(1)–C(2) 116.0(7), N(3)–C(1)–C(2) 126.2(7), N(2)–C(2)–C(1) 127.4(7), N(2)–C(2)–C(3) 128.0(6), C(1)–C(2)– C(3) 104.4(6), C(2)–C(3)–C(4) 104.0(6), C(2)–C(3)–C(8) 137.5(7), C(4)–C(3)–C(8) 118.5(7), N(l)–C(4)–C(3) 112.8(6), N(l)–C(4)–C(5) 125.7(7), C(3)– C(4)–C(5) 121.5(7), C(4)–C(5)–C(6) 118.5(8), C(5)–C(6)–C(7) 121.4(8), C(7)–C(6)–C(10) 118.5(8), C(6)–C(7)–C(8) 120.3(7).A B N R1 R2 R3 R4 C R4 R3 R2 R1 N N Me Me Me R1 R2 R3 R4 HN NEt3 1a–d 2a–d a R1 = R3 = H, R2 = R4 = CF3 b R1 = Br, R2 = R4 = H, R3 = NO2 c R1 = R4 = H, R2 = CF3, R3 = Cl d R1 = H, R2 = R3 = R4 = Cl Scheme 1Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) The authors would like to thank Dr. G. Alexandrov for the X-ray analysis. † General procedure for the synthesis of 2-triethylammonium-3-(3',5'- bistrifluoromethyl)phenylamino-4,6-ditrifluoromethylindolate 2a. A solution of 3,5-bis(trifluoromethyl)phenyl isocyanide 1a (1 g, 4.2 mmol) and triethylamine (0.35 ml, 2.5 mmol) in hexane (20 ml) was refluxed for 4 h.The resulting precipitate was filtered off, washed with hexane and recrystallised from acetonitrile. Yield 85%, mp 200–201 °C. 1H NMR ([2H6]DMSO) d: 1.05 (t, 9H, 3Me), 3.66–4.09 (m, 6H, 3CH2), 6.31 (s, 1H, 2'-H), 7.11 (s, 1H, 6'-H), 7.34 (s, 1H, 4'-H), 7.50 (s, 1H, 7-H), 7.93 (s, 1H, 5-H), 8.13 (s, 1H, NH). MS, m/z: 579 (100%, M+), 550 (67), 322 (21), 277 (21), 213 (44), 86 (40).Some physical characteristics for other compounds are given below: 2b: mp 224–226 °C. 1H NMR ([2H6]DMSO) d: 1.10 (t, 9H, 3Me), 3.66–4.05 (m, 6H, 3CH2), 6.32 (d, 1H, 6'-H, J 9.2 Hz), 7.90 (d, 1H, 4-H, J 2.2 Hz), 7.93 (dd, 1H, 5'-H, J5'-H,6'-H 9.2 Hz, J5'-H,3'-H 2.6 Hz), 7.95 (d, 1H, 6-H, J 2.2 Hz), 8.26 (s, 1H, NH), 8.40 (d, 1H, 3'-H, J 2.6 Hz).MS, m/z: 555 (3%, M+), 526 (13), 525 (48), 217 (31), 215 (33), 86(100). 2c: mp 245–246 °C. 1H NMR ([2H6]DMSO) d: 1.06 (t, 9H, 3Me, J 6.9 Hz), 3.87 (q, 6H, 3CH2, J 6.9 Hz), 6.60 (d, 1H, 6'-H, J 8.7 Hz), 6.99 (s, 1H, 2'-H), 7.05 (s, 1H, 7H), 7.33 (d, 1H, 5'-H, J 8.7 Hz), 7.72 (s, 1H, NH), 7.81 (s, 1H, 4-H). MS, m/z: 513 (66%, M + 2), 511 (100%, M+), 484 (59), 482 (89), 454 (32), 86 (49). 2d: mp 283–284 °C. 1H NMR ([2H6]DMSO) d: 1.05 (t, 9H, 3Me), 3.68–3.99 (m, 6H, 3CH2), 6.00 (d, 1H, 2'-H, J 2.5 Hz), 7.05 (d, 1H, 6'-H, J 2.5 Hz), 7.48 (s, 1H, NH), 7.88 (s, 1H, 4-H). MS, m/z: 513 (77%, M + 2) and other isotopic peaks, 511 (42%, M+), 484 (100), 456 (41), 179 (55), 86 (61), 72 (73). ‡ The experimental X-ray crystallographic data for 2a were obtained on an Enraf-Nonius, Cad-4 diffractometer (lMoKa, graphite monochromator, q/2q-scan, 2qmax = 46°).The structure was solved by a direct method and refined by a full-matrix least-squares method with an anisotropic approximation using the programs SHELX-93 to R = 0.078 (wR2 = 0.227) for 3689 independent reflections with F2 > 3sI; GOOF = 1.042. Empirical formula C24H21F12N3, monoclinic crystals, space group P21/c, a = 12.188(3) Å, b = 21.093(6) Å, c = 19.733(6) Å, b = 90.50(5)°, V = 5073(5) Å3, dcalc = 1.517 g cm–3, Z = 8, m = 0.152mm–1.Full lists of atomic coordinates, bond lengths, bond angles and thermal parameters have been deposited at the Cambridge Crystallographic Data Centre (CCDC). For details, see ‘Notice to Authors’, Mendeleev Communications, 1998, Issue1. Any request to the CCDC for data should quote the full literature citation and the reference number 1135/30. References 1 Ch. Grundmann, Chem. Ber., 1958, 91, 1380. 2 (a) B. Zeeh, Chem. Ber., 1968, 101, 1753; (b) B. Zeeh, Chem. Ber., 1969, 102, 1876. 3 Y. Ito, K. Kobayashi and T. Saegusa, J. Am. Chem. Soc., 1977, 99, 3532. 4 F. H. Allen, O. Kennard, D. G. Watson, L. Brammer, A. G. Orpen and R. Taylor, J. Chem. Soc., Perkin Trans. 2, 1987, 1. 5 I. Ugi and R. Meyer, Angew. Chem., 1958, 70, 702. Received: Moscow, 7th July 1998 Cambridge, 9th September 1998; Com. 8/05578E

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出版商:RSC    

年代:1998

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Mendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) A novel synthesis of 2-acylmethyleneimidazolidines Vyacheslav Ya. Sosnovskikh* and Michail Yu. Mel’nikov 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 The reaction of aliphatic b-amino-b-trichloromethyl vinyl ketones with ethylenediamine gives 2-acylmethyleneimidazolidines.We have shown recently1 that the reactions of aliphatic b-amino- b-trifluoromethyl vinyl ketones with ethylenediamine are very sensitive to steric factors under conditions of kinetic control (at room temperature without a solvent). For example, aminoenone 1a obtained from pinacolone and trifluoroacetonitrile affords, under these conditions, imidazolidine 2, whereas aminoenone 1b with a cyclohexyl substituent at the carbonyl group results in the formation of dihydrodiazepine 3.Taking into account these results and the ability of the CCl3 group to be substituted under the action of N-nucleophiles,2 we studied the reactions of aliphatic b-amino-b-trichloromethyl vinyl ketones 4a,b with ethylenediamine and found that this reaction occurs as a double nucleophilic attack at the b-carbon atom.However, unlike CF3-containing aminoenones, it is accompanied by substitution of the amino and trichloromethyl groups resulting in the formation of 2-acylmethyleneimidazolidines 5a,b. The yields of compounds 5a,b are 48% and 50%, respectively, since the reaction is complicated by the formation of by-products, which were not studied in detail.Compound 5c was previously3 obtained by the reactions of ethylenediamine with 4-dialkylamino-3-butyn-2-ones, which allows one to consider aminoenones 4 as synthetic equivalents of the relatively inaccessible b-aminoethynyl ketones. Theoretically, imidazolidines 5, as b-aminovinyl ketones, can exist in three tautomeric forms: ketoenamine (A), iminoenole (B) and ketoimine (C), and the content of the latter, based on the absence of the exo-methylene group signal in the 1H NMR spectra, does not exceed 5%.The compound 5c was described in ref. 3 as an enolic tautomer B, by analogy with 1-benzyl-2-(2-hydroxyprop-1-enyl)- 4,5-dihydroimidazole 6, to which structure B was ascribed on the basis of the spectroscopic and crystallographic data.†,4 It is noteworthy that the data presented in refs. 3 and 4 for compounds 5c and 6 do not contradict the ketoenamine tautomer A, since the bands at 3300 and 3270 cm–1 and the chemical shifts at 9.1 and 9.5 ppm assigned to the OH group can also be attributed to the hydrogen-bonded NH, and the crystallographic data only indicate the delocalised character of the C(2)–C(6) and C(6)–C(7) bonds in the crystals of dihydroimidazole 6.Furthermore, the Me group signals in these compounds are described as singlets implying the lack of the expected allylic coupling between the Me and =CH groups in 5c and 6 (which should be present in the enolic form B).5 The 1H NMR spectrum of compound 5a exhibits two multiplets AA'BB' due to the spin system of the CH2 group protons of the imidazolidine ring with centres at 3.51 and 3.67 ppm, a singlet due to the vinyl proton at 4.89 ppm, and broadened signals due to the NH protons at 4.83 and 9.34 ppm, the latter belonging to the hydrogen atom involved in the formation of the intramolecular hydrogen bond.When deuterioacetic acid is added, the signals of the vinyl and NH protons disappear and the multiplets of the CH2 groups merge to form a singlet at 3.82 ppm indicating a fast H/D exchange and formation of a symmetrically delocalised imidazolinium monocation 7a.A similar situation was observed for imidazolidine 5b.‡ † 2-(2-Hydroxyprop-1-enyl)-4,5-dihydroimidazole 5c.3 1HNMR (100MHz, CDCl3) d: 1.90 (s, 3H, Me), 3.55 (m, 4H, CH2CH2), 4.67 (s, 1H, =CH), 9.09 (s, 1H, OH).IR (KBr disc, n/cm–1): 3300 (OH), 1620 (C=C). 1-Benzyl-2-(2-hydroxyprop-1-enyl)-4,5-dihydroimidazole 6.4 The bond lengths C(2)–C(6) and C(6)–C(7) are both 1.39 Å, intermediate between a double and a single bond. 1H NMR (100 MHz, CDCl3) d: 2.0 (s, 3H, Me), 3.2–3.7 (m, 4H, CH2CH2), 4.3 (s, 2H, CH2Ph), 4.85 (s, 1H, =CH, exchanges with D2O), 7.4 (s, 5H, Ph), 9.5 (br.s, 1H, OH, exchanges with D2O). IR (KBr disc, n/cm–1): 3280, 1605, 1530 (br.). ‡ 2-Pivaloylmethyleneimidazolidine 5a. Aminoenone 4a (305 mg, 1.25 mmol) was dissolved in 300 ml (270 mg, 4.5 mmol) of ethylenediamine, and the reaction mixture was kept for 6–7 days at room temperature. The resulting crystals of imidazolidine 5a were washed with water and recrystallised from CCl4, yield 100 mg (48%), mp 183–184 °C. 1H NMR (250 MHz, CDCl3) d: 1.12 (s, 9H, But), 3.51 (m, 2H, CH2), 3.67 (m, 2H, CH2), 4.83 (br. s, 1H, NH), 4.89 (s, 1H, =CH), 9.34 (br. s, 1H, NH); after addition of CD3CO2D: 1.13 (s, 9H, But), 3.82 (s, 4H, CH2CH2). IR (Vaseline oil, n/cm–1): 3300, 3240, 3150 (NH), 3040 (=CH), 1620 (C=O), 1545 (br., C=C, NH). Found (%): C, 64.10; H, 9.81; N, 16.66.Calc. for C9H16N2O (%): C, 64.25; H, 9.59; N, 16.65. 2-Cyclohexylcarbonylmethyleneimidazolidine 5b. Yield 50%, mp 162–163 °C. 1H NMR (250 MHz, CDCl3) d: 1.1–1.8 (m, 10H, cyclohexyl), 2.1 (m, 1H, CH of cyclohexyl), 3.51 (m, 2H, CH2), 3.67 (m, 2H, CH2), 4.55 (br. s, 1H, NH), 4.72 (s, 1H, =CH), 9.30 (br. s, 1H, NH); after addition of CD3CO2D: 1.1–1.8 (m, 10H, cyclohexyl), 2.3 (m, 1H, CH of cyclohexyl), 3.80 (s, 4H, CH2CH2).IR (Vaseline oil, n/cm–1): 3310, 3230, 3140 (NH), 1620 (C=O), 1545 (br, C=C, NH). Found (%): C, 67.69; H, 9.36; N, 14.50. Calc. for C11H18N2O (%): C, 68.01; H, 9.34; N, 14.42. O R CF3 NH2 O But HN NH CF3 N CF3 NH (NH2CH2)2 – NH3 – NH3, –H2O 1a,b 2 3 a R = But b R = cyclohexyl O R CCl3 NH2 O R HN NH (NH2CH2)2 – NH3, –CHCl3 4a,b 5a–c a R = But b R = cyclohexyl c R = Me NR2 Me O ' (NH2CH2)2 –NHR2 ' O R N NH O R N NH O R N NH H H A B C 12 3 4 5 6 7 5a,b DO R D DN ND CD3CO2D O R DN ND D D 7a,bMendeleev Communications Electronic Version, Issue 6, 1998 (pp. 207–248) The fast exchange for deuterium of the NH and vinyl protons is expected as such behaviour is consistent with the tautomerism observed in various heterocyclic systems containing exocyclic b-carbonyl moieties.4,6 Unfortunately, based on the 1H NMR spectroscopic data, we cannot choose unambiguously between structures A and B for compounds 5a,b; however, taking into account the fact that � 95% of b-aminovinyl ketones exist in the ketoenamine form, which has a greater ability to stabilise as compared to iminoenols, 7 we prefer the enamine tautomer A, a choice favoured by the comparison of the IR and 1H NMR spectra of imidazolidine 5a and the corresponding b-aminovinyl ketone (5-amino-2,2- dimethyl-4-hexen-3-one§,8). The IR spectra of these compounds in Vaseline oil contain an intense absorption band in the region of 1620–1625 cm–1, which is characteristic of the C=O group coupled with the enamine fragment.In compounds 5b,c, this band is observed at 1620 cm–1, whereas for dihydroimidazole 64 it lies at 1605 cm–1. We have additionally confirmed the conclusion about the predominant contribution of the ketoenamine form A to the tautomeric equilibrium by the reaction of ethylenediamine with aminoenone 4d9 resulting in the formation of imidazolidine 5d.¶ § 5-Amino-2,2-dimethyl-4-hexen-3-one.8 1H NMR (80 MHz, CDCl3) d: 1.10 (s, 9H, But), 1.93 (s, 3H, Me), 5.1 (br.s, 1H, NH), 5.20 (s, 1H, =CH), 9.8 (br. s, 1H, NH). IR (Vaseline oil, n/cm–1): 3300, 3160 (NH2), 1625 (C=O), 1600, 1540 (C=C, NH2). ¶ 2-(1-Hydroxy-1-methylpropyl)carbonylmethyleneimidazolidine 5d. Yield 32%, mp 142–143 °C. 1H NMR (250 MHz, CDCl3) d: 0.83 (t, 3H, Me, J 7.3 Hz), 1.29 (s, 3H, Me), 1.61 (q, 1H, MeCHH, J 7.3 Hz), 1.62 (q, 1H, MeCHH, J 7.3 Hz), 3.57 (m, 2H, CH2), 3.72 (m, 2H, CH2), 4.73 (s, 1H, =CH), 4.81 (br. s, 1H, OH), 4.89 (br.s, 1H, NH), 8.87 (br. s, 1H, NH); after addition of CD3CO2D: 0.82 (t, 3H, Me, J 7.3 Hz), 1.28 (s, 3H, Me), 1.62 , 2H, MeCH2, J 7.3 Hz), 3.69 (s, 4H, CH2CH2). IR (Vaseline oil, n/cm–1): 3380, 3270, 3220 (OH, NH), 1615 (C=O), 1560 (br., C=C, NH). Found (%): C, 58.35; H, 8.66; N, 15.06.Calc. for C9H16N2O2 (%): C, 58.67; H, 8.75; N, 15.21. Unlike 5a–c, compound 5d contains a hydroxyl group in the a-position relative to the carbonyl and hence the keto form A stabilised by two intramolecular hydrogen bonds is more preferable a priori. Similar spectral parameters for 5a–c and 5d make it possible to assign the ketoenamine structure A to all these compounds, while the reaction of aminoenones 4a,b,d with ethylenediamine described in this work is a new and simple synthetic route to 2-acylmethyleneimidazolidines.This work was supported by the Russian Foundation for Basic Research (grant no. 96-03-33373). References 1 V. Ya. Sosnovskikh, M. Yu. Mel’nikov and I. A. Kovaleva, Izv. Akad. Nauk, Ser. Khim., 1998, 2305 (Russ.Chem. Bull., 1998, 47, 2234). 2 M. Cönen, J. Faust, S. Ringel and R. Mayer, J. Prakt. Chem., 1965, 27, 239. 3 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]. 4 M. W. Anderson, M. J. Begley and R. S. F. Jones, J. Chem. Soc., Perkin Trans. 1, 1984, 2599. 5 R. Mondelli and L. Merlini, Tetrahedron, 1966, 22, 3253. 6 G. R. Malone and A. I. Meyers, J. Org. Chem., 1974, 39, 713. 7 G. O. Dudek and R. H. Holm, J. Am. Chem. Soc., 1962, 84, 2691. 8 V. Ya. Sosnovskikh and I. S. Ovsyannikov, Zh. Org. Khim., 1990, 26, 2086 [J. Org. Chem. USSR (Engl. Transl.), 1990, 26, 1850]. 9 V. Ya. Sosnovskikh, Zh. Org. Khim., 1992, 28, 1307 [J. Org. Chem. (Engl. Transl.), 1992, 28, 1250]. O O H Et Me CCl3 NH2 (NH2CH2)2 – NH3, –CHCl3 O O H Et Me N NH H 4d 5d Received: Moscow, 2nd July 1998 Cambridge, 29th September 1998; Com. 8/05566A

ISSN:0959-9436     

出版商:RSC    

年代:1998

数据来源: RSC