摘要:

Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) A polymer of 8-O-glucosylated 2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid (Kdn) in the cell wall of Streptomyces sp. VKM Ac-2090 Alexander S. Shashkov,*a Galina M. Streshinskaya,b Larisa N. Kosmachevskaya,b Lyudmila I. Evtushenkoc and Irina B. Naumovab a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow, Russian Federation.Fax: +7 095 135 5328; e-mail: shash@ioc.ac.ru b Department of Biology, M. V. Lomonosov Moscow State University, 119899 Moscow, Russian Federation. E-mail: i_naumova@mail.ru c Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, 142292 Pushchino, Moscow Region, Russian Federation. Fax: +7 095 923 3602; e-mail: evtushenko@ibpm.serpukhov.su 10.1070/MC2000v010n05ABEH001338 The title polymer of Kdn was detected in biological object for the first time. 2-Keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid (Kdn) was first found in the form of an a-2,8-linked oligomer containing 6–7 residues in rainbow trout eggs.1 Later, Kdn was found in heterooligosaccharides of animal tissues2,3 and as a constituent of the capsular heteropolysaccharide of Klebsiella ozaenae serotype K4.4 We have detected polyKdn in the cell wall of Streptomyces sp.VKM Ac-2090 isolated from scab lesions potato. The polymers were extracted from the cell wall as described previously,5 and their structure was examined using NMR spectroscopy. The 13C NMR spectrum of the polymers (Figure 1) displayed the Kdn-containing polysaccharide as the major cell wall anionic polymer, along with several glycerol teichoic acids.The 1H and 13C NMR spectra of the predominant component of the polymer mixture were completely assigned using 2D homonuclear 1H/1H COSY, TOCSY and ROESY and heteronuclear 1H/13C HSQC (Figure 2) and HMBC experiments. The residue of nonulosonic acid was identified with Kdn in accordance with the coupling constants in the 1H NMR spectrum.6 The upfield chemical shift of H-3eq (2.205 ppm) was in agreement with the b-configuration of the Kdn residue.4 The second sugar residue in the disaccharide repeating unit of the polymer was identified as the terminal b-glucopyranose (b-Glcp) based on the chemical shifts and coupling constants of the 1H and 13C NMR spectra.The ROESY spectrum (Figure 3) revealed correlation peaks for the anomeric protons of Glcp and H-8, H-9 and H-9' of Kdn. The upfield chemical shift of C-9 and the downfield chemical shift of C-8 in the Kdn residue in comparison with that of nonsubstituted sugar (Table 1) allowed one to conclude that b-Glcp was bonded with Kdn by the 1®8 linkage. The presence of a correlation peak of H-1(Glcp)/C-8(Kdn) in the HMBC spectrum is consistent with this conclusion, too.The downfied shift of C-4 by 2 ppm in the 13C NMR spectrum of the b-Kdn residue Figure 1 13C NMR spectrum of the polymers of the cell wall of Streptomyces sp. VKM Ac-2090. Designations refer to the numbers of carbon atoms in the Kdn (K) and glucopyranose (G) residues. K1 G1 K2 K8 G3,5 G2 K6 K5 G4 K4 K7 K9 G6 K3 d/ppm 180 170 110 100 90 80 70 60 50 40 30 20 40 50 60 70 80 90 100 4.5 4.0 3.5 3.0 2.5 2.0 d/ppm d/ppm Figure 2 HSQC spectrum of the Kdn-containing polysaccharide of the cell wall of Streptomyces sp.VKM Ac-2090. The corresponding parts of the 1H and 13C NMR specta are displayed along the horizontal and vertical axes, respectively. Table 1 1H NMR data (D2O, 303 K, acetone: 2.225 ppm) for b-Kdn6 and for the polysaccharide of Streptomyces sp.VKM Ac-2090 cell wall. Residue Chemical shifts, d/ppm and coupling constants, J/Hz H-3ax H-3eq H-4 H-5 H-6 H-7 H-8 H-9 H-9' b-Kdn6 1.80 J3a,3e 12.0 2.23 J3e,4 5.0 4.02 J3a,4 12.0 3.56 J4,5 9.0 4.01 J5,6 9.0 3.88 J6,7 1 3.73 J7,8 8.5 3.63 J9,9' 11 J8,9 5.5 3.88 J8,9' 2 ®4)-b-Kdn- (2®8) 1.80 J3a,3e 13.0 2.20 J3e,4 5.0 3.98 J3a,4 12.3 3.57 J4,5 9.6 4.02 J5,6 9.6 4.09 J6,7 1.2 3.99 J7,8 8.5 3.94 J9,9' 12.5 J8,9 3.1 3.83 J8,9' 3.9 H-1 H-2 H-3 H-4 H-5 H-6 H-6' b-Glcp-(1 4.58 J1,2 7.9 3.33 J2,3 8.8 3.50 J3,4 8.8 3.38 J4,5 8.7 3.42 J5,6 1.7 3.82 J6,6' 12.1 3.68 J5,6' 5.7 Table 2 13C NMR data (D2O, 303 K, acetone: 31.45 ppm) for b-Kdn6 and for the polysaccharide of Streptomyces sp.VKM Ac-2090 cell wall. Residue Chemical shifts, d/ppm C-1 C-2 C-3 C-4 C-5 C-6 C-7 C-8 C-9 b-Kdn6 174.2 96.02 39.19 68.51 70.67 71.06 69.27 72.29 63.86 ®4)-b-Kdn- (2®8) 176.0 97.9 40.5 70.5 71.7 72.6 68.05 79.5 61.9 b-Glcp-(1 102.8 74.7 77.1 71.1 77.1 61.9Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) compared to that of non-substituted b-Kdn revealed the 2®4 linkage for the polysaccharide chain.The signals of the terminal monosaccharide residues were not detected. This fact allows us to suggest a high molecular mass of the polymer. Both of the comparable NOE correlation peaks H-1(Glcp)/H-8(Kdn) and H-1(Glcp)/H-9(Kdn) (Figure 3) and relatively large in module negative b-effect of glycosylation for C-9 of the Kdn residue were in agreement with the D-glycero-D-galacto-configuration of Kdn on the assumption of the b-D-configuration of the glucopyranose residue7,8 1.Until now, a polymer of Kdn has been found neither in procaryotic nor eucaryotic cells. The b-configuration of the glycoside bond in this natural sugar has not been reported previously. This communication is the first report on the polyKdn with the b-configuration of the glycoside bond.This work was supported in part by INTAS (grant no. 96- 1571) and the Russian Foundation for Basic Research (grant no. 98-04-49277). References 1 D. Nadano, M. Iwasaki, S. Endo, K. Kitajima, S. Inoue and Y. Inoue, J. Biol. Chem., 1986, 261, 11550. 2 M. Muhlenhoff, M. Eckhardt and R. Gerardy-Schahn, Curr. Opin. Struct. Biol., 1998, 8, 558. 3 F. A. Troy, Glycobiology, 1992, 2, 5. 4 Yu. A. Knirel’, N. A. Kocharova, A. S. Shashkov, N. K. Kochetkov, V. A. Mamontova and T. F. Soloveva, Carbohydr. Res., 1989, 188, 145. 5 Yu. M. Kozlova, G. M. Streshinskaya, A. S. Shashkov, L. I. Evtushenko and I. B. Naumova, Biokhimiya, 1999, 64, 805 [Biochemistry (Engl. Transl.), 1999, 64, 671]. 6 C. Auge and C. Gautherton, J. Chem. Soc., Chem. Commun., 1987, 859. 7 G. M. Lipkind, A. S. Shashkov, S. S. Mamyan and N. K. Kochetkov, Carbohydr. Res., 1988, 181, 1. 8 A. S. Shashkov, G. M. Lipkind, Yu. A. Knirel and N. K. Kochetkov, Magn. Reson. Chem., 1988, 26, 735. Figure 3 Part of the ROESY spectrum of the Kdn-containing polysaccharide of the cell wall of Streptomyces sp. VKM Ac-2090. The corresponding parts of the 1H NMR spectum are displayed along the horizontal and vertical axes. Designations refer to the numbers of protons in the Kdn (K) and glucopyranose (G) residues. 4.55 4.60 4.0 3.8 3.6 3.4 3.2 d/ppm G1/8,9K G1/9' K G1,5 d/ppm O O HOH2C O O COOH HO HO CH2OH OH OH HO 1 Received: 8th June 2000; Com. 00/1664

ISSN:0959-9436     

出版商:RSC    

年代:2000

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) (h6-Naphthalene)tricarbonylchromium-mediated hydrogenation of 3,5-diene-1,7-diynes as a route to (Z,Z,Z)-1,4,7-trienes Edward P. Serebryakov,*a Andrei A. Vasil’ev,a Dmitrii Yu. Titskiib and Irina P. Beletskayab a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow, Russian Federation. Fax: + 7 095 135 5328; e-mail: ser@cacr.ioc.ac.ru b Department of Chemistry, M.V. Lomonosov Moscow State University, 119899 Moscow, Russian Federation. Fax: + 7 095 939 1854 10.1070/MC2000v010n05ABEH001327 The hydrogenation of internal 3,5-diene-1,7-diynes over (h6-naphthalene)tricarbonylchromium affords homoconjugated (Z,Z,Z)-1,4,7-trienes as major products. (h6-Arene)tricarbonylchromium complexes (ATCC) are known to catalyse 1,4-cis-hydrogenation of conjugated dienes1,2 and 1,2-syn-hydrogenation of acetylenes,2,3 which leads to (Z)-disubstituted olefins in both cases.Recently, ATCC were successfully used as catalysts for the simultaneous hydrogenation of both diene and acetylene groups in conjugated alkyl 2,4-diene-6-ynoates, which afforded the corresponding ‘skipped’ (Z,Z)-alka-3,6-dienoates. 4 The high selectivity of this process suggests that ATCC exhibit a higher affinity to the diene moiety than that to the triple bond. Now, we have obtained conjugated enyne substrates of another type, where acetylenic groups are attached to the termini of an internal 1,3-diene system (compounds 1a–c), and studied their ATCC-induced hydrogenation.Starting dienediynes 1a,b were prepared by the Pd-promoted cross-coupling5 of (E,E)-1,4-diiodobuta- 1,3-diene 26 (readily accessible via Pt-catalysed oxidative dimerization of acetylene in iodine-containing solutions) either with but-3-yn-1-ol 3a alone or with undec-1-yne 3b and 3a consecutively (Scheme 1). Pyrrolidine was found to be the best solvent for the crosscoupling of alkynes 3a,b with diiodide 2 (see ref. 7 for an original procedure). Its advantage is that the reaction in this solvent needs no assistance of copper co-catalysts (since the latter can promote the unwanted dimerization of alkynes). Thus, when the traditional CuI–Et3N combination in benzene5 was tried, it brought about the accumulation of monosubstituted products along with unconverted 2 despite complete consumption (IR monitoring) of more than 2 equivalents of an aliphatic alkyne. By contrast, the reaction of 2 with alkynol 3a (2 equivalents) in pyrrolidine led to symmetrical dienediyne 1a in 81% yield.Attempts to prepare the monosubstituted iododienyne by condensing 2 with only 1 equivalent of 3a were unsuccessful, because the selectivity of mono-alkylation was low.As the consequence, both simultaneous and consecutive addition of 3a and 3b (1 equivalent of each) to diiodide 2 invariably resulted in a mixture of three or more products. Nevertheless, for the preparation of unsymmetric dienediynes, the use of two acetylenes of different polarity remains reasonable. In such a case, the target material can be readily separated from symmetric by-products by flash chromatography. In fact, the sequential cross-coupling of diiodide 2 with 3b and 3a (1.2 equivalents of each) followed by chromatography on SiO2 afforded nonadeca-5,7-diene-3,9-diynol 1b in 44% yield.† Symmetric diol 1a was also isolated in this operation.To facilitate further manipulations, 1a was converted into its diacetate 1c.‡ For the planned transformation of diendiynes 1b,c into skipped (Z,Z,Z)-trienes by ATCC-mediated hydrogenation (h6-naphthalene) tricarbonylchromium (NTCC) in THF was obviously the catalyst of choice because it is effective at temperatures as low as 45 °C.2 Under these conditions, methylene-separated (Z,Z,Z)- trienes 4b,c were obtained as the major products.Their 13C NMR spectra displayed the signals (d ~25 ppm) of methylene groups flanked by adjacent C=C bonds (=CH–CH2–CH=), which were equally diagnostic for the Z-configured ‘skipped’ double bonds.4(b),(c),8,§ Once again, the predominance of this molecular array corroborates a higher affinity of the ‘Cr(CO)3’ species2 to 1,3-dienes with respect to triple bonds.In contrast to the clean transformation of alkyl alka-2,4-dien- 6-ynoates into skipped (Z,Z)-dienes,4 the selectivity of hydrogenation for dienediynes 1b and 1c was no higher than 75%.Both the 1H NMR spectra at 300 MHz and mass spectra (electron ionization at 70 eV) (the [M + 2]+ peak with Irel = 15% in addition to the molecular ion of 4b with Irel = 8%) showed that the target trienes were contaminated by products with the same carbon skeleton, but with only two double bonds separated by two or more methylene groups.This result was not unprecedented, because chromium carbonyls are known to induce 1,3-hydrogen † (E,E)-Nonadeca-5,7-diene-3,9-diyn-1-ol 1b. Into a degassed solution of diiodide 2 (306 mg, 1 mmol), PdCl2·(PPh3)2 (35 mg, 0.05 mmol) and PPh3 (35 mg) in dry pyrrolidine (1.5 ml) undec-1-yne 3b (183 mg, 1.2 mmol) and but-3-yn-1-ol 3a (84 mg, 1.2 mmol) were consecutively injected within a 10 min interval with stirring, and the reaction was monitored by TLC. In 1 h the mixture was worked up as described earlier7 and subjected to column chromatography on SiO2 (eluents: 5, 10 and 20% EtOAc in hexane) to afford 120 mg (44%) of the title compound as white crystals, mp 59–60 °C.UV (EtOH, lmax/nm): 292 and 310. 1H NMR (CDCl3) d: 0.90 (t, 3H, J 7.2 Hz), 1.20–1.45 (m, 12H), 1.52 (quint., 2H, J 6.9 Hz), 1.84 (br. s, 1H), 2.32 (br. t, 2H, J 7.0 Hz), 2.61 (br. t, 2H, J 7.0 Hz), 3.72 (t, 2H, J 6.8 Hz), 5.60 (br. d, 1H, J 14.1 Hz), 5.67 (br. d, 1H, J 14.1 Hz), 6.43–6.60 (several peaks, 2H). 13C NMR (CDCl3) d: 14.1 (Me), 19.8, 22.7, 24.1, 28.7, 28.9, 29.1, 29.3, 29.5, 31.9 and 61.1 (CH2), 79.7, 81.7, 90.4 and 95.3 (C), 112.3, 114.0, 139.7 and 140.5 (CH).‡ (E,E)-Dodeca-5,7-diene-3,9-diyne-1,12-diol 1a was prepared in a similar manner (yield 81%) by treating 2 with 3a (2 equiv.). 1H NMR (CDCl3) d: 1.75 (br. s, 2H), 2.75 (br. t, 4H, J 6.6 Hz), 3.75 (t, 4H, J 6.6 Hz), 5.26 (br. d, 2H, J 14.2 Hz), 6.60 (several peaks, 2H). (E,E)-1,12-Diacetoxydodeca-5,7-diene-3,9-diyne 1c was prepared conventionally (Ac2O–Py) and isolated by column chromatography as white crystals (mp 69–70 °C).UV (EtOH, lmax/nm): 292 and 308. 1H NMR (CDCl3) d: 2.09 (s, 6H), 2.68 (br. t, 4H, J 6.6 Hz), 4.17 (t, 4H, J 6.6 Hz), 5.24 (br. d, 2H, J 15.4 Hz), 6.52 (several peaks, 2H). 13C NMR (CDCl3) d: 20.1 (CH2), 20.9 (Me), 62.2 (CH2), 81.1 (C), 89.9(C), 113.1 (CH), 140.2 (CH), 170.8 (C=O). § Dienediynes 1b or 1c (0.1 g in 5 ml of THF in both cases) were hydrogenated over NTCC (0.1–0.15 g) in a 50 ml stainless-steel autoclave (50 atm of H2, 45–60 °C, 2 h).The reaction mixtures were filtered, concentrated in vacuo, and subjected to column chromatography (hexane– benzene, 1:1; then hexane–EtOAc, 4:1) to afford compound 4b (0.04 g, 40%) or 4c (0.056 g, 56%) as yellowish oil contaminated with 25–30 mol% of the corresponding overhydrogenation products. (Z,Z,Z)-Nonadeca-3,6,9-trienol 4b: 1HNMR (CDCl3) spectrum is consistent with that reported earlier.10 13C NMR (CDCl3) d: 14.1 (Me), 22.7 (CH2), 25.6 (CH2), 25.7 (CH2), 27.2 (CH2), 29.3 (CH2), 29.5 (two peaks, CH2), 29.6 (two peaks, CH2), 30.8 (CH2), 31.9 (CH2), 62.2 (CH2), 125.6 (CH), 127.5 (CH), 127.7 (CH), 128.6 (CH), 128.7 (CH), 130.5 (CH), 131.2 (CH), there is a good agreement with the data for the lower C12 and C15 homologues of 4b.8(b),(c) EI MS, m/z: 278 ([M1]+, 4b, C19H34O) and 280 ([M2]+, dihydro-4b, C19H36O).(Z,Z,Z)-1,12-Diacetoxydodeca-3,6,9-triene 4c: 1H NMR (CDCl3) d: 2.01 (s, 6H), 2.40 (q, 4H, J 6.6 Hz), 2.82 (br. t, 4H, J 6.1 Hz), 4.09 (t, 4H, J 6.6 Hz), 5.30–5.55 (several peaks, 6H). 13C NMR (CDCl3) d: 20.9 (Me), 25.7 (CH2), 26.9 (CH2), 63.7 (CH2), 124.9 (CH), 128.2 (CH), 130.6 (CH), 170.9 (C=O).Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) shifts in linear 1,4-dienes2 and methyl linolenate,9 a structurally related triene, which gives rise to a conjugated diene system. In an atmosphere of H2, the latter undergoes 1,4-cis-hydrogenation to give an isolated C=C bond.The formation of diolefinic contaminants, ‘dihydro-4b’ and ‘dihydro-4c’, may be tentatively represented by Scheme 2. Because the separation of triolefins 4 from their dihydro congeners is technically feasible, e.g., by using silica gel impregnated with AgNO3, and all the intermediates shown in Scheme 1 can be readily prepared from acetylene, the short route from diodide 2 to molecules like 4b seems to be synthetically attractive. Actually, alcohol 4b is a known intermediate for the synthesis of (Z,Z,Z)-nonadeca-1,3,6,9-tetraene 5, the sex pheromone of the winter moth Operophtera brumata.9 Our synthesis of homoconjugated (Z,Z,Z)-trienes represents a new approach to compounds of this chemotype, among which are eicosanoids and a number of lepidopteran insect pheromones (for earlier methodologies, see ref. 10). This work was supported by the Russian Foundation for Basic Research (grant no. 99-03-32992) and, in part, by INTAS (grant no. 97 1874). References 1 E. N. Frankel, E. Selke and C. A. Glass, J. Am. Chem. Soc., 1968, 90, 2446. 2 M. Sodeoka and M. Shibasaki, Synthesis, 1993, 643. 3 M. Sodeoka and M. Shibasaki, J. Org. Chem., 1985, 50, 1147. 4 (a) A. A. Vasil’ev, G. V. Kryshtal and E. P. Serebryakov, Mendeleev Commun., 1995, 41; (b) A. A. Vasil’ev, A. L. Vlasyuk, G. D. Gamalevich and E. P. Serebryakov, Bioorg. Med. Chem., 1996, 4, 389; (c) A. A. Vasil’ev and E. P. Serebryakov, Zh. Org. Khim., 1998, 34, 1033 (Russ. J. Org. Chem., 1998, 34, 981). 5 K. Sonogashira, in Metal-Catalysed Cross-Coupling Reactions, eds.F. Diederich and P. Stang, Wiley, New York, 1998, pp. 203–229. 6 S. A. Mitchenko, V. P. Ananikov, I. P. Beletskaya and Yu. A. Ustynyuk, Mendeleev Commun., 1997, 130. 7 M. Alami, F. Ferri and G. Linstrumelle, Tetrahedron Lett., 1993, 34, 6403. 8 (a) W. Boland and L. Jaenicke, Liebigs Ann. Chem., 1981, 92; (b) J. Sandri and J.Viala, J. Org. Chem., 1995, 60, 6627; (c) R. K. Bhatt, J. R. Falck and S. Nigam, Tetrahedron Lett., 1998, 39, 249. 9 (a) E. N. Frankel and R. O. Butterfield, J. Org. Chem., 1969, 34, 3930; (b) E. N. Frankel, E. Selke and C. A. Glass, J. Org. Chem., 1969, 34, 3936; (c) E. N. Frankel, J. Org. Chem., 1972, 37, 1549. 10 W. Huang, S. P. Pulaski and J. Meinwald, J. Org. Chem., 1983, 48, 2270. 11 (a) S. Durand, J.-L. Parrain and M. Santelli, J. Chem. Soc., Perkin Trans. 1, 2000, 253; (b) K. Mori, in The Total Synthesis of Natural Products, ed. J. Apimon, Wiley, New York, 1992, vol. 9, pp. 79–85. Scheme 1 Reagents and conditions: i, HOCH2CH2CºCH (3a, 2 equiv.), PdCl2(PPh3)2–PPh3/pyrrolidine, room temperature, 1 h (81%); ii, n-C9H19- CºCH (3b, 1.2 equiv.), then 3a (1.2 equiv.), PdCl2·(PPh3)2–PPh3/ pyrrolidine, room temperature, 1 h (44%); iii, Ac2O–Py, room temperature, 1 h (95%); iv, H2 (50 atm)–(h6-naphthalene)Cr(CO)3/THF, 45–60 °C, 2 h (ca. 56% for 4c and 40% for 4b, not optimised). I I (CH2)2OR RO(CH2)2 (CH2)2OH n-C9H19 2 1c (R = Ac) 1a (R = H) iii i ii 1b iv iv AcO OAc 4c n-C9H19 OH 4b n-C9H19 5 R2 R1 1,4-H2 R2 R1 1 1,2-H2 (2x) R2 R1 4 R2(1) R1(2) 1,4-H2 R2(1) R1(2) R1(2) R2(1) R1(2) R2(1) dihydro-4 dihydro-4' Scheme 2 1,4-H2 [~1,3-H] Received: 22nd May 2000; Com. 00/1653

ISSN:0959-9436     

出版商:RSC    

年代:2000

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) Reluctant formation of a titanium(IV) arene complex Paul Kiprof,* Brett C. Steurer, Duane D. Fansler and Mark A. Erickson Department of Chemistry, University of Minnesota Duluth, Duluth, MN 55812, USA. Fax: +1 218 726 7394; e-mail: pkiprof@d.umn.edu 10.1070/MC2000v010n05ABEH001244 A new high-valent hexaethylbenzene complex of titanium is formed in the reaction of hexaethylbenzene with TiCl4, when AlCl3 is used.High-valent transition metal arene complexes are still scarce. In spite of recent discoveries in the field, it is not well understood, how they form, especially the ionic complex [h6-C6Me6TiCl3]+ [Ti2Cl9]–, which can be obtained from TiCl4 and hexamethylbenzene, has been a mystery (equation 1).1–3 In the past, it has been shown that less substituted arenes, even pentamethylbenzene, which is lacking only one methyl group, as compared with hexamethylbenzene, do not form stable arene complexes in the same way as hexamethylbenzene does.4 We have previously shown that, assuming an equilibrium exists between TiCl4 and the free arene on the one side and the arene complex on the other side, the number of alkyl substituents plays an important role in the stability of the arene complex.Six methyl groups are necessary to form a stable complex in the reaction with TiCl4. This phenomenon is unprecedented in lowvalent transition metal arene chemistry. According to ab initio calculations, every methyl group contributes 5–6 kcal mol–1 to the binding energy of the arene to the TiCl3 + fragment.5 In the case of pentamethylbenzene this is enough to shift the equilibrium completely to the reactant side.In fact, indications of an arene complex could be only obtained by using neat TiCl4 as the solvent. We reacted hexaethylbenzene with TiCl4 in dichloromethane and did not observe the formation of an arene complex as would be indicated by substantial shifts in the 1H and 13C NMR spectra.Instead, we observed the signal of the free arene. The brown colour of the solution indicated the presence of chargetransfer complexes. Even in neat TiCl4 as a solvent,4 we could not observe the formation of a stable arene complex (Scheme 1). This result was very puzzling, especially in light of the lowvalent transition metal arene chemistry, where hexamethylbenzene and hexaethylbenzene can be used interchangeably.6 Following the procedure of Calderazzo et al.,7 the reaction was then repeated in benzene or toluene as a solvent and AlCl3 was added to remove the chloride ion from TiCl4, in order to form the cationic titanium species, and an arene complex could be obtained (Scheme 1).† The obtained complex was clearly identified by NMR spectroscopy, where it exhibits shifts in the 1H and 13C NMR spectra to more positive values compared to the free arene, which clearly indicate the complexation of the arene to the TiCl3 + centre.Ab initio molecular orbital calculations revealed that hexaethylbenzene should have essentially the same binding energy to the TiCl3 + fragment as hexamethylbenzene (83.98 vs. 84.94 kcal mol–1).‡,8,9 The calculated geometry around the titanium atom is virtually identical to that of the hexamethylbenzene complex (Figure 1). There are no close Ti–H and Ti–C (other than ring carbons) distances (from possible agostic interactions), and the ethyl groups are rotated so that they are pointing up and down in an alternating fashion. The Cl atoms are located beneath the ring C atoms that have an ethyl group pointing up.This research was supported by an award from Research Corporation. We also would like to thank the University of Minnesota Graduate School for support of this project and the Minnesota Supercomputer Institute and the UMD Digital Imaging Laboratory for a generous allocation of computer resources. † General experimental details: All manipulations were performed in a dry argon atmosphere and using standard Schlenk glassware.Solvents were dried according to standard procedures. All chemicals were obtained from Acros. To a solution of AlCl3 (0.65 g, 4.87 mmol) in benzene (10.0 ml), hexaethylbenzene (1.00 g, 4.06 mmol) was added followed by the addition of 0.67 ml (6.06 mmol) of TiCl4.The colour of the solution went from pale-yellow to dark red-brown after the addition of TiCl4. The solution was left stirring for 3 h and the product was filtered off and washed with benzene (10 ml). This produced 1.97 g of product (90.8% yield based on hexaethylbenzene). After recrystallization from dichloromethane, 1.31 g of purified product was obtained (60.4% based on hexaethylbenzene). 1H NMR (300 MHz, CD2Cl2) d: 1.47 (t, 12H, CH2Me, J 7 Hz), 3.11 (q, 18H, CH2Me, J 7 Hz). 13C NMR (75.4 MHz, CD2Cl2) d: 14.91 (CH2Me), 27.00 (CH2Me), 155.74 (ring carbons). Found (%): C, 36.93; H, 5.21. Calc. for C18H30AlCl7Ti (%): C, 37.97; H, 5.31. C6Me6 + 3TiCl4 [h6-C6Me6TiCl3]+[Ti2Cl9]– (1) ‡ All calculations were done using the program GAMESS.8 The basis set used was a combination of an effective core potential basis set for titanium by Hay and Wadt and of a double-zeta basis set by Dunning and Hay (see ref. 10). The basis was augmented with d functions (Cl: z = 0.619 and C: z = 0.72). No symmetry was implied in the calculations. The structures were optimised at the Hartree-Fock level and then, single point frozen core MP2 energy calculations were performed for each structure.The formation energy was obtained from the difference of the energies of optimised hexaethylbenzene and TiCl3 + and the energy of the titanium complex. The binding energy is the negative of the formation energy. C6Et6 + 3TiCl4 [h6-C6Et6TiCl3]+[Ti2Cl9]– C6Et6 + TiCl4 + AlCl3 TiCl3 AlCl4 – Scheme 1 C Cl Cl Cl Ti C C C C C C C C C C C C C C C C C Figure 1 Calculated structure of the cation hexaethylbenzene trichlorotitanium( IV).All Ti–C distances are between 2.56 and 2.57 Å and all Ti–Cl distances are 2.18 Å.Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) References 1 H. L. Krauss and H. Hüttmann, Z. Naturforsch., Teil B, 1963, 18, 976. 2 H. L. Krauss, H. Hüttmann and U. Deffner, Z. Anorg. Allg. Chem., 1965, 341, 164. 3 (a) E. Solari, C. Floriani, A. Chiesi-Villa and C. Gustiani, J. Chem. Soc., Chem. Commun., 1989, 1747; (b) E. Solari, C. Floriani, K. Schenk, A. Chiesi-Villa, C. Rizzoli, M. Rosi and A. Sgamellotti, Inorg. Chem., 1994, 33, 2018. 4 K. Brügermann, R. S. Czernuszewicz and J. K. Kochi, J. Phys. Chem., 1992, 96, 4405. 5 P. Kiprof, J. D. Thompson and B. C. Steurer, Internet J. Chem., 1998, 1, 29. 6 B. Mailvaganam, B. G. Sayer and M. J. McGlinchey, Organometallics, 1990, 9, 1089. 7 (a) F. Calderazzo, I. Ferri, G. Pampaloni and S. Troyanov, J. Organomet. Chem., 1996, 518, 189; (b) F. Calderazzo, G. Pampaloni and A. Vallieri, Inorg. Chim. Acta, 1995, 229, 179. 8 M.W. Schmidt, K. K. Baldridge, J. A. Boatz, S. T. Elbert, M. S. Gordon, J. H. Jensen, S. Koseki, N. Matsunaga, K. A. Nguyen, S. J. Su, T. L. Windus, M. Dupuis and J. A. Montgomery, J. Comput. Chem., 1993, 14, 1347. 9 (a) P. J. Hay and W. R. Wadt, J. Chem. Phys., 1985, 82, 270; (b) T. H. Dunning and P. J. Hay, in Methods of Electronic Structure Theory, ed. H. F. Schaefer III, Plenum Press, New York, 1977, pp. 1–27. Received: 6th December 1999; Com. 99/1570

ISSN:0959-9436     

出版商:RSC    

年代:2000

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) Aromatic stabilization of organochalcogen compounds with the intramolecular X�O (X = S, Se, Te) coordination Vladimir I. Minkin* and Ruslan M. Minyaev Institute of Physical and Organic Chemistry, Rostov State University, 344090 Rostov-on-Don, Russian Federation. Fax: +7 8632 28 5667; e-mail: minkin@ipoc.rsu.ru 10.1070/MC2000v010n05ABEH001349 The ab initio MP2/LanL2DZ calculations predict a significant contribution of cyclic p-electron delocalization to the stabilization of the trans–cis–cis conformation of derivatives of b-chalcogenovinylaldehydes 1 with the intramolecular Chalc�O coordination.The origin of a sufficiently high strength, as well as structural and chemical consequences, of the attractive interaction between electron-abundant centres suitably oriented within a molecule is of considerable interest.1–4 It was found that molecular conformations of a variety of organochalcogen (X = S, Se, Te)3–6 and organopnictogen (X = P, As, Sb, Bi)7,8 compounds are controlled by the XO or XN interactions, which draw these closedshell centres together to distances much shorter than the sum of the respective van der Waals radii.This interaction is especially strong, and the X–O distances are short in organochalcogen compounds 1 (X = S, Se, Te). The above bond closes a conjugated chain to form a five-membered ring containing an aromatic p-electron sextet or decet, as is the case with 1,6-dioxa-6a-chalcapentalenes 5 or their pnictogen analogues. The high strength of the ChalcO and ChalcN interactions is illustrated by the computational findings1,6 that the trans–cis–cis conformation of compounds 1 (X = Chalc, Y = O, NR', R = H) with the tricoordinate T-shaped chalcogen centre is preferable to the cis–cis–cis conformation of 2, ensuring the formation of a sufficiently strong intramolecular hydrogen bond similar to that characteristic of b-hydroxyvinylaldehyde (malonic aldehyde) 2 (X = Y = O), or the sterically unstrained trans–trans–trans conformation of 3.For example, conformation 1 (X = S, Y = O, R = H) with the intramolecular coordination S�O bond was calculated (MP2/6- 31+G**) to be preferable by 4.0 kcal mol–1 in terms of energy compared to conformation 2, in which a sufficiently strong intramolecular S–HO hydrogen bond occurs. In compounds 1, 4 and 5, the covalency ratio factors9 calculated for the XO bonds from the experimental or theoretically calculated distances between the formally nonbonded atoms may be as high as 0.8–0.9.Thus, these bonds are almost indistinguishable in their strength and length from the corresponding covalent or three-centre, four-electron hypervalent bonds.The energies of these secondary (‘preliminary hypervalent’1) bonds in compounds 1 (X = Chalc) were evaluated as differences between the total energies of their cis- and trans-isomers. According to the ab initio (MP2/6-31G** and MP2/LanL2DZ) calculations, 6 the attractive interaction increases in the order S, Se and Te and with increasing electronegativity of a substituent R attached to the chalcogen centre.Isomer 1 (X = S, R = H) is 1.2 (MP2/LanL2DZ) or 0.3 kcal mol–1 (MP2/6-31+G**) less stable than its unstrained isomer 3, whereas in the tellurium (X = Te, R = H) analogues, cis-isomer 1 is 3.8 kcal mol–1 (MP2/LanL2DZ) energy preferable to 3.6 By replacing the substituent R = H by a more electronegative chlorine atom in 1 (X = Te), the energy of the Te–O bond may be increased up to 16.5 kcal mol–1 (MP2/ Lanl2DZ).In 1,6-dioxa-6a-chalcapentalenes 4 � 5, the energies of the 3c, 4e O–X–O bonds estimated in a similar way were found to be 12.1, 19.8 and 27.7 kcal mol–1 (MP2/LanL2DZ) for X = S, Se and Te, respectively.6 The principal factors responsible for attractive forces between the closed-shell atomic centres in compounds 1 and 4 are the negative hyperconjugation, i.e., the donor–acceptor nO ® s* X–R ineraction, electrostatic interaction and resonance, i.e., aromatic stabilization of the five-membered ring formed by the secondary X–O bond.1–4,6,10 The goal of this work was to evaluate a contribution of the aromatic stabilization of five-membered rings in compounds 1 using an approach based on homodesmotic reactions.Reactions of this type enable the contribution from the cyclic electron delocalization to be singled out, their energies (HSE) being considered as the analogues of the Dewar resonance energies.11 Although no unambiguous homodesmotic reaction (in which the number of bonds of each formal type is retained in both reactants and products) can be constructed for compounds 1, reaction (1) may serve as a reasonable approximation.The only deviation from the above condition is the difference between the numbers of Csp3–H and Csp2–H bonds in reactants (4 and 5, respectively) and products (3 and 6, respectively). However, a small difference in the energies of Csp3–H and a Csp2–H bonds is included into the HSE values of all compounds 1 and hence does not affect the principal conclusions.The total energies of all structures involved in equation (1) were calculated by the MP2(fc)/LanL2DZ method using the Gaussian-94 and Gaussian-98 packages of ab initio programs. The orbital basis selected allows accounting for some relativistic effects (via effective core potentials), which are important for post-third-row atoms. The optimisation of a molecular geometry at stationary points was performed with a ‘tight’ convergence criterium.To exclude the extraneous stabilization of bimolecular X Y R XO H R X O Y X Y Y X Y Y X Y Y X Y 1 2 3 4a 5a 5b 4b X = S, Se, Te Y = O, NR' Table 1 Ab initio MP2(fc)/LanL2DZ data for bimolecular complexes 6. X R Etot/hartree dXO/Åa aFor comparison, the van der Waals contacts are 3.30, 3.40 and 3.60 Å and the bond lengths are: 1.75, 1.90 and 2.08 Å for SO, SeO and TeO, respectively.12 bEstab = Ecomplex – (EMeXR + ECH2O).Eb stab / kcal mol–1 S H –164.236319 3.465 0.66 Cl –178.383916 2.833 4.13 Se H –163.355948 3.402 1.18 Cl –177.519004 2.817 5.17 Te H –162.185171 3.409 1.78 Cl –176.366829 2.872 6.27 X O R 1 (Y = O) H H H O H H CH4 R X Me O H H O H H H H 6 (1)Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) complexes 6 through formation of additional hydrogen bonds (X–HO and/or CHCl) between the components,6 their energies were calculated for the conformation whose stability is provided by solely the RXO interaction (only the RXO distance was optimised, all other geometric parameters were taken to be equal to their values in monomers, the angles XO=C and Me–XO were taken constrained at 120° and 90°, respectively). Table 1 contains the results of calculations for complexes 6.As expected, the stabilization energy of the bimolecular associates increases, and the XO distances diminish in the order X = S, Se and Te with R = H, Cl. The HSE values calculated by equation (1) underestimate the stabilising effects of cyclic electron delocalization in compounds 1 by the value of the angle strain of a cis-structure.To take this effect into account, the strain energies Estr of cis-isomers 1 were calculated according to equation (2). The aromatic stabilization energies ASE = HSE – Estr of pseudo-heterocycles 1 are given in Table 2. The ASE values are indicative of a substantial contribution of the cyclic p-electron delocalization to the overall stabilization of compounds 1 with the intramolecular Chalc�O coordination of the hypervalent type.The HSE values of pseudo-heterocycles 1 constitute 10–40% of the HSE value of the prototypic aromatic system of benzene (28.9 kcal mol–1) calculated at a similar level of approximation. This finding lends support to the consideration of derivatives of b-chalcogenovinylaldehydes 1 (X = Te or Se; R = Cl) as true heterocycles, 1,2-oxatellurolyl-1-ium and 1,2-oxaselenolyl-1-ium chlorides,14 respectively, wronic structure was described as a resonance hybrid of the structures with delocalised six-electron p-systems.The chemical behaviour of compounds 1 (the retention of the structural type in reactions with electrophiles and easy ionization of the R–X bond under treatment with supernucleophiles) corresponds to the aromatic structure 1a � 1b � 1c rather than heterodiene 1.The treatment of the type 1 fragments as heterocyclic moieties has been recently used as the basis for the design of new mimic-fused bicyclic heterocycles consisting of stable nonbonded 1,5-type SO interaction.10 This work was supported by the Russian Foundation for Basic Research (grant nos. 00-15-97320 and 98-03-33169a). V. I. M. gratefully acknowledges the support of the Alexander von Humboldt Foundation (Humboldt Research Award 1999). References 1 J. G. Ángyán, R. A. Poirier, A. Kucsman and I. G. Csizmadia, J. Am. Chem. Soc., 1987, 109, 2237. 2 D. H. R. Barton, M.B. Hall, Z. Lin, S. I. Parekh and J. Reibeuspies, J. Am. Chem. Soc., 1993, 115, 5056. 3 W. R. McWhinnie, I. D. Sadekov and V. I. Minkin, Sulfur Rep., 1996, 18, 295. 4 V. I. Minkin, Ross. Khim. Zh., 1999, 43, 10 (in Russian). 5 A. Kucsman and I. Kapovits, in Organic Sulfur Chemistry: Theoretical and Experimental Advances, eds. I. G. Csizmadia, A. Mangini and F. Bernardi, Elsevier, Amsterdam, 1985, pp. 191–245. 6 R. M. Minyaev and V. I. Minkin, Can. J. Chem., 1998, 76, 766. 7 A. J. Arduengo III and C. A. Stewart, Chem. Rev., 1994, 94, 1215. 8 T. Murafuji, T. Mutoh, K. Satoh, K. Tsunenari, N. Azuma and H. Suzuki, Organometallics, 1995, 14, 3848. 9 A. E. Reed, L. A. Curtiss and F. Weinhold, Chem. Rev., 1988, 88, 899. 10 Y. Nagao, T. Hirata, S. Goto, S. Sano, A. Kakechi, K.Iizuka and M. Shiro, J. Am. Chem. Soc., 1998, 120, 3104. 11 V. I. Minkin, M. N. Glukhovtsev and B. Ya. Simkin, Aromaticity and Antiaromaticity: Electronic and Structural Aspects, Wiley, New York, 1994. 12 A. Bondi, J. Phys. Chem., 1964, 68, 441. 13 R. L. Disch and J. M. Schulman, Chem. Phys. Lett., 1988, 152, 402. 14 M. R. Detty, B. J. Murray, D. L. Smith and N. Zumbulyadis, J.Am. Chem. Soc., 1983, 105, 875. Table 2 Aromatic stabilization energies of cyclic compounds 1 calculated according to equations (1) and (2) by the ab initio MP2(fc)/LanL2DZ method.a aThe total energies (hartree) of the components of equations (1) and (2) calculated by the MP2(fc)/LanL2DZ method are the following: CH4 –40.278267, CH2=O –114.042055, EtCH=O –192.270511. bThe negative sign of energy corresponds to destabilization. X R 1, Etot/hartree 7, Etot/hartree 1, dXO/Å 7, dXO/Å DE (1 – 3)6/ kcal mol–1 HSE/kcal mol–1 Estr /kcal mol–1 ASE/kcal mol–1 S H –200.998260 –216.328403 2.980 2.917 –3.6b 2.0 –6.6 8.6 Cl –215.146857 –202.175967 2.395 2.567 5.0 2.6 –3.6 6.2 Se H –200.120475 –201.297980 2.935 2.909 0.9 3.6 –5.1 8.7 Cl –214.288736 –215.467236 2.307 2.541 10.5 6.9 –1.2 8.1 Te H –198.531140 –200.130677 2.845 2.907 3.8 5.6 –2.9 8.5 Cl –213.145592 –214.319632 2.294 2.568 16.5 12.5 –1.6 14.1 X O R 7 H O H H CH4 R X Me O H H 6 (2) Me O H X Y R 1a X Y R 1b X Y R 1c Received: 26th June 2000; Com. 00/

ISSN:0959-9436     

出版商:RSC    

年代:2000

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) Inramolecular hypervalent O®Cl interaction in the chloronium cations: an ab initio study Ruslan M. Minyaev* and Vladimir I. Minkin Institute of Physical and Organic Chemistry, Rostov State University, 344090 Rostov-on-Don, Russian Federation. Fax: +7 8632 28 5667; e-mail: minyaev@ipoc.rsu.ru 10.1070/MC2000v010n05ABEH001366 The ab initio [MP2(fu)/6-31G**] and DFT (B3LYP/6-31+G**) calculations predict that the strong hypervalent O®Cl interaction stabilises the cyclic and bicyclic heteropentalene structures of chloronium cations.Attractive inter- and intramolecular interactions of the hypervalent type play an important role in the stabilization of sterically hindered conformations of organoelement compounds1 and are responsible for secondary and tertiary structures of proteins, which are crucial for recognition processes.2,3 In the last decade, both experimental and theoretical works have been devoted to the elucidation of the nature of the intramolecular hypervalent O®X(Y) interactions in compounds 1–3, where X and Y are chalcogens (X = S, Se, Te; R = H, Me, Cl)1,4 or pnictogens (Y = = N, P, As, Sb, Bi).5,6 The energy of these hypervalent interactions was found to strongly depend on the electronegativity of chalcogen atoms X and substituents R.4,6 Similar hypervalent interactions were also observed in organoelement compounds.7–9 At the same time, weak attractive intermolecular interactions between chalcogens (O, S) and chlorine were experimentally observed in the bimolecular complexes H2O···ClF,10 SO2···ClF11 and H2S···ClF.12 The noncovalent O···I contact length observed in a crystal of PhIO 4 with the T-shaped geometry around the iodine centres is considerably shorter than the sum of the van der Waals radii of O and I (3.32 Å).13 Therefore, it may be expected that similar intramolecular attractive O®Hal hypervalent interactions also exist in halogencontaining organic compounds 5 and 6 (X = Hal+ and R = H, Me, Ph, F, Cl), isoelectronic to 1 or 2.Here, we report on the ab initio [MP2(fu)/6-31G**]14 and DFT (B3LYP/6-31+G**)14 calculations of chloronium cations 5 (R = H, F) and 6, which evidenced for rather strong attractive O®Cl interactions in these cations. To estimate the energy of the O®Cl interaction, cations 5 (R = = H, F) and 6 were compared with their trans-trans-isomers 7 (R = H, F) and 8, which are free of the O®Cl interaction.According to the calculations, all structures of 5–8 correspond to genuine minima (l = 0, hereafter l designates the number of hessian negative eigenvalues at a given stationary point) on the corresponding potential-energy surfaces (PES).Figures 1 and 2 and Table 1 demonstrate the calculated molecular structures, geometries and energy parameters of cations 5–8. All of the calculated bond lengths and angles are consistent with the available experimental data on chloronium cations (see ref. 15). As can be seen in Table 1 and Figure 1, the cis-cis forms of compounds 5 (R = H or F) are stabilised by the O®Cl interaction, whose energy substantially depends on the substituent at the chlorine.For compound 5 with an electropositive substituent R = H, the O®Cl interaction energy was predicted to be 7.1 (MP2) and 5.6 (DFT) kcal mol–1, whereas, in the case of an electronegative substituent R = F, this energy increases up to 20.3 (MP2) and 19.3 (DFT) kcal mol–1. The nonbonded O···Cl dis- X O R XO R O X OO N Y O 1a 1b 2 3 O I Ph O I Ph O I Ph O n 2.37 Å 2.06 Å 4 Cl O R ClO R O Cl O O Cl O 5a 5b 6a 6b O Cl R O Cl O H 7 8 Table 1 Ab initio [MP2(fu)/6-31G**] and DFT (B3LYP/6-31+G**) data for cations 5–8.a aEtot (a.u.) and DE (kcal mol–1) are the total and relative energies (1 a.u.= = 627.5095 kcal mol–1); ZPE (a.u.) is the harmonic zero-point correction; DEZPE (kcal mol–1) is the relative energy including the harmonic zero-point correction; DH (kcal mol–1) is the relative enthalpy under standard conditions P= 1 atm and T= 298.1 K; w1 (cm–1) is the smallest harmonic vibration frequency.bSingle-point calculations at the MP2 geometry. Structure MethodEtot DEZPE DEZPEDHw1 5, Cs MP2 –650.63832300.0632940 0142 R = H DFT –651.76373400.0614280 0148 5, Cs MP2 –749.58313500.0575370 0163 R = F DFT –750.93959600.0561130 0162 6, C2v MP2 –801.63884900.0823960 0179 DFT –803.17191400.0802090 0194 7, C1 MP2 –650.627010 7.1 0.061814 6.2 6.6 100 R = H DFT –651.754787 5.6 0.059694 4.5 5.0 91 7, C1 MP2 –749.550728 20.3 0.055466 19.0 19.4 62 R = F DFT –750.908761 19.3 0.053964 18.0 18.8 56 8, Cs MP2 –801.584553 34.1 0.078684 31.7 31.9 72 DFTb–803.098488 46.1 Figure 1 Geometry parameters of cations 5 (R = H, F) and 7 (R = H, F) calculated by the ab initio [MP2(fu)/6-31G**] and DFT (B3LYP/6-31+G**) methods (in parentheses).The bond lengths and angles are indicated in angström units and degrees, respectively. 5 (R = H), Cs 5 (R = F), Cs 7 (R = H), C1 7 (R = F), C1 O Cl F O O O Cl Cl Cl F 2.557 (2.564) 1.229 (1.216) 1.487 (1.492) 1.329 (1.322) 1.804 (1.855) 119.5 (119.7) 119.3 (118.2) 95.4 (95.4) 2.036 (2.072) 1.255 (1.244) 1.448 (1.456) 1.339 (1.334) 1.752 (1.786) 116.9 (117.4) 116.7 (116.2) 91.2 (91.2) 1.806 (1.879) 1.327 (1.320) 1.502 (1.522) 1.217 (1.204) 1.653 (1.687) 1.704 (1.725) 1.348 (1.353) 1.499 (1.511) 1.220 (1.207) 1.695 (1.715)Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) tance in 5 (R = F) is ~0.5 Å shorter than that in 5 (R = H).The C–C lengths calculated for 5 (R = H or F) indicate that the structure of 5 (R = F) is also more delocalised than that of 5 with R = H. Note that the degree of equalization of C–C bonds in 5 (R = H or F) is higher than that in unstrained trans–trans conformers 7 (R = H or F) (Figure 1). This fact is indicative of the partially aromatic character of five-membered pseudo-heterocycles 5.The structures of 7 (R = H or F) have C1 symmetry since the substituent at the chlorine is out of the molecular plane. The corresponding planar trans–trans structures of Cs symmetry are transition states for the internal rotation of the substituent R around the Cl–C bond. The energy barriers for this rotation were found to be about 8 kcal mol–1.The heteropentalene system of 6, in which the effects of both the 10p-electronic stabilization and the hypervalent O®Cl interaction act cooperatively, may exhibit a stronger hypervalent bonding than that of compounds 5. Indeed, according to the calculations, chloronium cation 6 corresponds to a minimum (l = 0, the smallest harmonic frequency is w1 = 179 cm–1, see Table 1) on the PES of C5H4O2Cl+.The structure of 8, in which no effects of the 10p-electronic stabilization and the hypervalent O®Cl bonding are present, is predicted to be 34.1 (MP2) or 46.1 (DFT) kcal mol–1 thermodynamically less stable than that of 6. Note that DFT calculations do not reveal a minimum corresponding to a stable structure like 8. To estimate the energy difference between the structures of 6 and 8, the latter was calculated by DFT in a single point with the MP2 optimised geometry.In conclusion, we found that the strong attractive hypervalent O®Cl interaction exists in chloronium cations 5 and 6. It may be expected that this interaction will increase in similar bromonium and iodonium cations. This work was supported by the Russian Foundation for Basic Research (grant nos. 98-03-33169a and 00-15-97320) and by the Ministry of Education (grant no. 97-9.1-288). References 1 V. I. Minkin, Ross. Khim. Zh., 1999, 43, 10 (in Russian). 2 A. C. Legon and D. J. Millen, in Principles of Molecular Recognition, eds. A. D. Buckingham, A. C. Legon and S. M. Roberts, Blackie Academic and Professional, London, 1993, pp. 16–42. 3 J.-M.Lehn, Supramolecular Chemistry, VCH, Weinheim, 1995. 4 R. M. Minyaev and V. I. Minkin, Can. J. Chem., 1998, 76, 766. 5 A. J. Arduengo, III and C. A. Stewart, Chem. Rev., 1994, 94, 1215. 6 E. G. Nesterova, T. N. Gribanova. R. M. Minyaev and V. I. Minkin, Izv. Akad. Nauk, Ser. Khim., in press. 7 R. R. Holmes, Chem. Rev., 1996, 96, 927. 8 J. G. Vercade, Acc. Chem. Res., 1993, 26, 483. 9 V. Pestunovich, V. Sidorkin and M. Voronkov, in Progress in Organosilicon Chemistry, eds. B. Marcinies and J. Chojnowski, Gordon and Breach Science Publishers, New York, 1994, ch. 5, p. 69. 10 S. A. Cooke, G. Cotti, C. M. Evans, J. H. Holloway and A. C. Legon, Chem. Commun., 1996, 2327. 11 G. Cotti, J. H. Holloway and A. C. Legon, Chem. Phys. Lett., 1996, 255, 401. 12 H.I. Bloemink, K. Hinds, J. H. Holloway and A. C. Legon, Chem. Phys. Lett., 1995, 242, 113. 13 P. J. Stang and V. V. Zhdankin, Chem. Rev., 1996, 96, 1123. 14 M. J. Frish, G. W. Trucks, H. B. Schlegel, P. M.W. Gill, B. G. Johnson, M. A. Robb, J. R. Cheeseman, T. A. Keith, G. A. Petersson, J. A. Montgomery, K. Raghavachari, M. A. Al-Laham, V. G. Zakrzewski, J. V. Ortiz, J. B. Foresman, C. Y. Peng, P. Y. Ayala, W. Chen, M. W. Wong, J. L. Andres, E. S. Replogle, R. Gomperts, R. L. Martin, D. J. Fox, J. S. Binkley, D. J. Defrees, J. Baker, J. P. Stewart, M. Head- Gordon, C. Gonzalez and J. A. Pople, Gaussian-94, Revision B.3, Gaussian, Inc., Pittsburgh PA, USA, 1995. 15 C. H. Reynolds, J. Am. Chem. Soc., 1992, 114, 8676. 6, C2v 8, Cs O Cl 1.707 1.851 1.335 1.478 1.216 1.436 1.339 1.388 Cl O O O 1.966 (1.941) 87.5 (87.2) 1.772 (1.837) 1.382 (1.381) 1.384 (1.392) 1.296 (1.288) Figure 2 Geometry parameters of cations 6 and 8 calculated by the ab initio [MP2(fu)/6-31G**] and DFT (B3LYP/6-31+G**) methods (in parentheses). The bond lengths and angles are given in angström units and degrees, respectively. Received: 26th June 2000; Com. 00/1692

ISSN:0959-9436     

出版商:RSC    

年代:2000

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) Selective bromination of alkanes and arylalkanes with CBr4 Vladimir V. Smirnov,*a Vladimir M. Zelikman,a Irina P. Beletskaya,a Mikhail M. Levitskii*b and Marina A. Kazankovaa a Department of Chemistry, M. V. Lomonosov Moscow State University, 119899 Moscow, Russian Federation. Fax: +7 095 932 8846; e-mail: smirnov@kinet.chem.msu.ru b N.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 117813 Moscow, Russian Federation. Fax: +7 095 135 5085; e-mail: levitsk@ineos.ac.ru 10.1070/MC2000v010n05ABEH001342 The catalytic bromination of alkanes, cycloalkanes and arylalkanes with near 100% yields was performed using CBr4 as a brominating agent in the presence of copper- and nickel-containing catalysts.We performed the selective catalytic bromination of alkanes (decane and dodecane), cycloalkanes (cyclohexane) and arylalkanes (toluene and p-xylene) by CBr4 in the presence of metal (Cu and Ni) complex catalysts for the first time. Previously,1 CBr4 was used in a combination with sodium hydroxide for the bromination of alkanes and cycloalkanes in a two-phase system in the presence of a phase-transfer catalyst.However, this process is ineffective: the reaction time was as long as 90 h even for reactive substrates, and the product yields were no higher than 30–70%. Carbon tetrabromide as the constituent of a catalytic complex with AlBr3 was also used for the bromination of alkanes and cycloalkanes.2 In this case, the CBr4·2AlBr3 complex can also serve as a brominating agent in the absence of molecular bromine.3 A required twofold molar excess of aluminium bromide and the sensitivity of the brominating agent to moisture make this synthesis difficult to perform.Analogously, in a similar process4 of alkane bromination with methylene bromide in the presence of SbF5, large relative amounts of the metal halide were used (the molar ratio CHBr2:SbF5 was about two).The aim of this study was to develop a selective procedure for alkane bromination by CBr4 in the presence of catalytic amounts of a transition metal. Copper complexes prepared by the reactions of CuBr with quaternary ammonium bromides, for example, CuBr + Bu4NBr (1:1) (catalyst 1),† the [(PhSiO1.5)2CuO]n metal-containing polyphenylsiloxane immobilised on silica (catalyst 2)‡ and the related nickel derivative {[H2N(CH2)3SiO1.5]2NiO}n (catalyst 3)‡ were used as the catalysts.Previously,5–7 copper chloride complexes similar to 1 and organometallic polysiloxanes (containing phenyl, alkyl and aminoalkyl substituents at silicon) grafted onto silica were used in the metathesis of C–Cl and C–H bonds in the CCl4–alkane systems.These catalytic systems are stable, highly active and easy to use. Chloroform and monochloroalkanes were prepared with 98–99% selectivity at 50–80% conversion of the parent alkanes in reactions with the participation of CCl4 and these catalysts. The reactions of CBr4 with alkanes and arylalkanes in the presence of 1–3 proceed at elevated temperatures (150–180°) in 100% (dodecane, decane, toluene and xylene) or near 100% (cyclohexane) yields of monobromoalkanes in terms of the initial CBr4.§ An induction period was absent.Table 1 summarises the yields of reaction products at different conditions. The reaction is highly selective: cyclohexane gives only cyclohexyl bromide, and toluene and xylene, monobromides of the benzyl structure.Isomer mixtures of secondary bromoalkanes were obtained from decane and dodecane; 1-bromoalkanes and dibromo derivatives were absent from the products or occurred as traces. We failed to identify particular isomers by GC–MS because of the similarity of the mass spectra of linear secondary bromoalkane isomers. The bromination of n-dodecane at 150 °C in the presence of catalyst 1 gave five isomeric secondary bromides in the ratio 1.3:1.2:1.0:1.4:0.9 (to within ±0.1); the selectivity for particular isomers varied within narrow limits from 16 to 24% (±2%) in † Chemically pure carbon tetrabromide was triply recrystallised from ethanol.Dodecane, decane, cyclohexane, bromoform, and dodecyl bromide were distilled and thoroughly dried before use. Tetrabutylammonium bromide prepared by the interaction between tributylamine and n-bromobutane was azeotropically dried and twice recrystallised from benzene.The catalytic complex was prepared from chemically pure CuBr and the quaternary salt by dissolving the components in the reaction mixture on heating (40–50 °C). ‡ The cage organometallic siloxane oligomers were prepared by wellknown methods.10,11 The structure of the compounds was confirmed by the presence of absorption bands typical of Si–O–Si (1030–1100 cm–1, 2 and 3), Si–O–Cu (950–980 cm–1, 2), Ph–Si (1130 cm–1, 2) and NH2 (750, 3380 cm–1, 3) groups in the IR spectra; a typical band at 750 nm in the electronic absorption spectrum of 2 (d–d transitions in the Cu2+ ion); and elemental analysis data.In all of the compounds, the Si:M atomic ratio was close to 2.For a precursor of 2 found (%): Cu, 18.2; Si, 16.4; C, 45.3; H, 2.7. C12H10Si2O4Cu requires (%): Cu, 18.8; Si, 16.6; C, 45.6; H, 3.0. For a precursor of 3 found (%): Ni, 19.0; Si, 18.5; C, 24.7; H, 5.0. C6H16N2Si2O4Ni requires (%): Ni, 19.9; Si, 18.9; C, 24.4; H, 5.4. Catalysts supported on silica (Silochrome C-80) were prepared by sorption from toluene or toluene–DMF solutions.After the removal of the solvent, the catalysts were heated at 160 °C in a vacuum. The copper or nickel content of heterogeneous catalyst 2 or 3 was 0.11 or 0.16 wt.%, respectively. § The bromination was performed in sealed ampoules under temperature- controlled conditions with stirring. The amount of a catalyst was 2 mol% on a hydrocarbon basis for complex 1 or 1 g of a heterogeneous catalyst per 10 ml of the reaction mixture. Oxygen was removed by repeated freeze–pump–thaw cycles (the residual pressure was 10–3 mmHg).Products were analysed by GLC and GC–MS (a Finnigan MAT-212 instrument coupled with a Varian 3740 chromatograph). The mass spectra of monobromodecanes exhibited a peak of the [M – Br]+ ion (m/z = 169) and a set of peaks corresponding to alkyl chain fragmentation (m/z = 43, 57, 71, 85, 113).The absence of a peak of the stable ion C4H8Br+ (m/z = = 135, 137)12 suggests that 1-bromodecane is not a reaction product. The released hydrogen bromide was determined by acid–base titration. Table 1 Bromination of alkanes by CBr4. Entry Alkane (RH) RH:CBr4 molar ratioCatalyst t/h T/°C Yield of RBr (%) (on a CBr4 basis) 1 C12H26 10:1 1a aEquimolar mixture of CuBr and Bu4NBr (10 wt.% of the weight of reactants).bYields higher than 100% indicate that more than one bromine atom from a molecule of CBr4 took part in the formation of bromoalkanes. 2.5 180 67 2 C10H22 5:1 1 8 160 93 3 C12H26 10:1 1 5 180 95 4 cyclo-C6H12 10:1 1 10 180 86 5 C12H26 10:1 2 2.5 160 130b 6 C12H26 10:1 2 5 150 68 7 C12H26 2.2:1 2 5 150 61 8 C12H26 10:1 2 10 130 55 9 C12H26 10:1 2 10 98 28 10 C10H22 10:1 2 5 150 60 11 cyclo-C6H12 10:1 2 8 150 48 12 C12H26 10:1 3 2.5 150 155b 13 cyclo-C6H12 10:1 3 10 150 67 14 Toluene 10:1 3 10 150 160b 15 Toluene 5:1 3 10 150 145b 16 p-Xylene 10:1 3 5 150 135bMendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) the absence of 1-bromododecane.Temperatures above 150 °C are required to obtain 100% yields in several hours. At 98–130 °C, the reaction rate decreases; however, as follows from Table 1 (entries 8 and 9), it remains measurable. This is a dissimilarity from analogous reactions with the participation of CCl4, which proceed very slowly below 150 °C. The ratio between reactant has almost no effect on the yield (cf.entries 6, 7 and 14, 15 in Table 1). Undoubtedly, the bromination in the presence of copper complexes has radical nature and can be represented by the following reaction scheme taking into account published data5–9 concerning reactions with the participation of CCl4 and CCl3Br: where {CuI} and {CuIIBr} are bromide complexes of CuI and CuII. It is likely that the reaction is responsible for the catalytic character of the overall process.Reaction (4) leads to the target product and, simultaneously, to the regeneration of an active form of the catalyst. Only CuI rather than CuII was found in the reaction mixture after the reaction completed. The reaction in the presence of homogeneous catalyst 1 corresponds to the equation A material balance on bromine for entry 4 in Table 1 is written as follows: 3 mmol of CBr4 gave 2.4 mmol of bromoform, 2.6 mmol of bromocyclohexane, 0.15 mmol of HBr, and 0.45 mmol of unreacted CBr4.The discrepancy between the initial amount of bromine (12 mmol of Br atoms) and the value found from the chemical analysis of products (11.75 mmol) does not exceed the measurement error.Thus, a side reaction with the formation of HBr plays an insignificant role in the material balance. In contrast, in the presence of heterogenised catalysts 2 and 3, comparable amounts of HBr (20–50% of the initial CBr4) were found; methylene bromide was also detected at high conversions. More than 1 mol of a monobromoalkane per mole of parent CBr4 can be obtained with the use of the most reactive hydrocarbons (dodecane and alkylbenzenes) and highly active catalysts 2 and 3 (Table 1, entries 5, 12, 14–16).This fact, as well as the formation of CH2Br2 and the yields of bromoalkanes higher than that of bromoform by 10–20% in some experiments with catalyst 1, can be explained by the participation of CHBr3 in the reaction. It is likely that the following reactions occur in the system in the presence of CBr4 and catalysts 2 and 3: The role of these reactions increases with the conversion of CBr4 and hence with the CHBr3:CBr4 ratio.As a result, the yield of bromoform on 2 and 3 at high conversions was lower than that of a monobromoalkane by 30–50%. We found in special experiments with a mixture of CBr4 and CHBr3 in place of initial CBr4 that bromoform was really consumed in the presence of CBr4.Thus, a mixture of dodecane, CHBr3 and CBr4 in the molar ratio 10:3.5:1 (150 °C, the reaction time 2.5 h) gave a mixture of secondary monobromododecanes in 59% yield referred to parent CBr4. In this case, the RH:CHBr3:CBr4 ratio after the reaction was 9.4:3.2:0.7 rather than 9.4:3.5:0.4 expected for the process with no participation of bromoform.In the absence of CBr4, which takes part in chain initiation, bromoform reacts with alkanes and arylalkanes very slowly on all of the catalysts. Thus, the results suggest that the reaction with CBr4 is an effective and convenient method for alkane and arylalkane functionalisation. Its advantages are high conversion of parent CBr4, near 100% selectivity for secondary bromoalkanes and bromocycloalkanes, and the absence of hazardous and toxic reagents. This work was supported by the Russian Foundation for Basic Research (grant nos. 00-03-32211 and 00-03-32813).References 1 P. R. Schreiner, O. Lauenstein, I. V. Kolomitsyn, S. Nadi and A. A. Fokin, Angew. Chem., Int. Ed. Engl., 1998, 37, 1895. 2 M. E. Vol’pin, I. S. Akhrem and A. V.Orlinkov, New J. Chem., 1989, 13, 771. 3 I. S. Akhrem, A. V. Orlinkov, L. V. Afanas’eva and M. E. Vol’pin, Izv. Akad. Nauk, Ser. Khim., 1996, 1208 (Russ. Chem. Bull., 1996, 45, 1148). 4 G. A. Olah, An-hsiang Wu and O. Farooq, J. Org. Chem., 1989, 54, 1463. 5 E. N. Golubeva, A. I. Kokrin, N. A. Zubareva, P. S. Vorontsov and V. V. Smirnov, J. Mol. Catal., A, 1999, 146, 343. 6 V. V.Smirnov, E. N. Golubeva, O. V. Zagorskaya, S. M. Nevskaya, M. M. Levitskii and V. Yu. Zufman, Kinet. Katal., 2000, 41, 439 (in Russian). 7 V. V. Smirnov, M. M. Levitskii, I. G. Tarkhanova, S. M. Nevskaya and E. N. Golubeva, Kinet. Katal., 2000, 41, in press. 8 G. A. Russel, C. Deboer and K. M. Desmond, J. Am. Chem. Soc., 1963, 85, 365. 9 J. M. Tedder and R. A. Watson, Trans. Faraday Soc., 1966, 62, 1215. 10 A. A. Zhdanov and M. M. Levitskii, in Uspekhi v oblasti sinteza elementoorganicheskikh polimerov (Advances in the Synthesis of Organoelement Polymers), ed. V. V. Korshak, Nauka, Moscow, 1988, pp. 143–231 (in Russian). 11 V. A. Igonin, O. I. Shchegolikhina, S. V. Lindeman, M. M. Levitsky, Yu. T. Struchkov and A. A. Zhdanov, J. Organomet. Chem., 1992, 423, 351. 12 NIST/EPA/NIH Mass Spectral Database, version 4.5, 02.1994. {CuI} + CBr4 {CuIIBr} + CBr3 · CBr3 · + RH CHBr3 + R· R· + CBr4 RBr + CBr3 ·, (1) (2) (3) {CuIIBr} + R· {CuI} + RBr (4) CBr4 + R'H CHBr3 + R'Br R· + CHBr3 CHBr· 2 + RBr CHBr· 2 + RH CH2Br2 + R·. (4a) (3a) Received: 19th June 2000; Com. 00/1668

ISSN:0959-9436     

出版商:RSC    

年代:2000

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) The first example of a tweezer-like structure in diterpene derivatives of the kaurane series Vladimir A. Alfonsov, Galina A. Bakaleynik, Aidar T. Gubaidullin, Vladimir E. Kataev,* Galina I. Kovyljaeva, Alexander I. Konovalov, Igor A. Litvinov, Irina Yu. Strobykina, Olga V. Andreeva and Maya G. Korochkina A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the Russian Academy of Sciences, 420088 Kazan, Russian Federation.Fax: +7 8432 75 2253; e-mail: kataev@iopc.kcn.ru 10.1070/MC2000v010n05ABEH001314 The first compound with a tweezer-like structure in diterpene derivatives of the kaurane series was obtained in the reaction of the acid chloride of isosteviol with diethylene glycol.The literature provides a great number of examples on the molecular receptors for binding organic and natural compounds, and considerable attention has been directed towards these studies in steroid chemistry.1 Cholic acid was used as the starting point for obtaining so-called tweezer-like molecules where two tetracyclic steroid moieties are linked together through a conformationally flexible chain and placed above each other to form a cavity capable of binding different guest molecules.1 These compounds show association with glucopyranosides2 and are known for their DNA binding affinity.3 Analogous tweezer-like molecules can also be obtained using diterpene derivatives of the kaurane series 2.Like cholic acid, they have a rigid tetracyclic framework but differ by the position of ring D and the way in which rings A and B are condensed (cis for steroid 1 and trans for compounds 2).We suppose that such bis-isosteviol compounds will also exhibit binding affininity, which can differ from properties of steroid-based receptors. Note that starting material isosteviol 2a forms molecular complexes with medium-sized molecules.4 The key rigid tetracyclic fragment of the tweezer-like diterpene derivatives, namely, (4a,8b,13b)-13-methyl-16-oxo-17-norkauran- 18-oic acid (isosteviol, 2a), was obtained earlier by the acid hydrolysis of glycoside stevioside extracted from the plant Stevia rebaudiana Bertoni.5 A convenient starting reagent for binding two diterpenes into a tweezer-like structure is acid chloride 2b, which was synthesised by the reaction of isosteviol 2a with an excess of thionyl chloride.†,6 In fact, product 3 obtained by the reaction of compound 2b with diethylene glycol in the 2:1 ratio in the presence of triethylamine‡ appears to have a tweezer-like structure according to single crystal X-ray diffraction (Figure 1).§ The unit cell of bis-isosteviol derivative 3 contains one symmetrically independent molecule of 3.The oxyethylene chain binding the two isosteviol fragments has mainly syn-clinal conformation, which is in agreement with published data10 on the structure of 1,2-dioxy-substituted ethanes. The torsion angles (°) are as follows: O(1B)–C(21B)–C(22B)–O(1) 71.7(9), C(21B)– C(22B)–O(1)–C(22A) –156.4(7), C(22B)–O(1)–C(22A)–C(21A) –73.2(12), O(1)–C(22A)–C(21)–O(1A) –48.5(15). The distances between the ether oxygen atom O1 and the carbonyl oxygen atoms O(2A) and O(2B) of two isosteviol fragments are 4.43 Å and 4.51 Å, respectively. Tetracyclic fragments of compound 3 are located above each other in the crystal, forming a cavity.The cavity size can be characterised by the distances between the carbonyl atoms O(16A) and O(16B) (5.54 Å), the carbon atoms of methyl groups C(20A) and C(20B) (4.97 Å) and the atoms C(6A) and C(6B) of cyclohexane rings B (7.09 Å).Me CO2H Me HO Me OH HO A B C D OH Me Me Me CO2H OH OH Me Me C(O)R Me H H O A B D O Me Me Me O R 1 2a R = OH 2b R = Cl O Me Me Me O O O O Me Me Me O O 3 † A mixture of isosteviol 2a (0.5 g, 1.57 mmol) and freshly distilled thionyl chloride (0.5 ml, 2.5 mmol) was refluxed for 1 h.The unreacted excess of thionyl chloride was removed at a reduced pressure. The residue was recrystallised from hexane to give 2b; mp 143–145 °C (yield 0.36 g, 68%). IR spectrum (mineral oil, n/cm–1): 1740 (C=O, ketone), 1800 (ClC=O). Found (%): Cl, 9.93. Calc. for C20H29ClO2 (%): Cl, 10.52. ‡ A solution of diethylene glycol (0.045 ml, 0.47 mmol) and triethylamine (0.13 ml, 0.93 mmol) was added to a solution of acid chloride 2b (0.32 g, 0.9 mmol) in carbon tetrachloride (5 ml).The reaction mixture was refluxed for 37 h. Then, it was washed with water and dried over CaCl2. The compound was isolated by column chromatography (silica gel, CCl4) and then recrystallised from hexane to give 3; mp 153–155 °C (yield 0.24 g, 71%).IR spectrum (mineral oil, n/cm–1): 1130, 1180, 1720 (ester); 1740 (ketone). Found (%): C, 74.27; H, 9.83. Calc. for C44H66O7 (%): C, 74.75; H, 9.41. § Single-crystal X-ray data collection for compound 3 was performed on an Enraf-Nonius CAD4 four-circle diffractometer (graphite monochromator, CuKa radiation, w/2q scan method, q £ 74.3°) using a colourless prismatic crystal (crystal dimensions 0.45×0.35×0.30 mm).Twenty five centered reflections gave a refined orthorhombic unit cell of the dimensions a = 12.137(4), b = 18.24(1), c = 18.462(8) Å, V = 4086(4) Å3, Z = 4, dcalc = 1.149 g cm–3. A total of 4388 reflections were measured, of which 2631 were unique with I > 3s(I). The structure was solved in the space group P212121 by direct methods using the SIR program7 and by difference Fourier syntheses.All non-hydrogen atoms were refined anisotropically, while hydrogen atoms were refined isotropically. The final R values were R = 0.064, Rw = 0.086 for 2349 unique reflections with F2 � 3s. All calculations were carried out on a DEC Alpha Station 200 computer with the MolEN system.8 The selected bond distances and torsion angles were obtained using the PLATON program.9 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., Issue 1, 2000. Any request to the CCDC should quote the full literature citation and the reference number 1135/68.Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) References 1 P. Wallimann, T. Marti, A. Furer and F. Diederich, Chem. Rev., 1997, 97, 1567. 2 P. Schiessl and F. P. Schmidtchen, J. Org. Chem., 1994, 59, 509. 3 H. Hsieh, J. G. Muller and C. J. Burrows, J. Am. Chem. Soc., 1994, 116, 12077. 4 V. A. Alfonsov, G. A. Bakaleynik, V. E. Kataev, G. I. Kovyljaeva, A. I. Konovalov, I.Yu. Strobykina, O. V. Andreeva and M. G. Korochkina, Mendeleev Commun., 1999, 227. 5 V. A. Alfonsov, G. A. Bakaleynik, A. T. Gubaidullin, V. E. Kataev, G. I. Kovyljaeva, A. I. Konovalov, I. A. Litvinov and I. Yu. Strobykina, Zh. Obshch. Khim., 1998, 68, 1813 (Russ. J. Gen. Chem., 1998, 68, 1735). 6 V. A. Alfonsov, G. A. Bakaleynik, V. E. Kataev, G. I. Kovyljaeva, A. I. Konovalov, I.Yu. Strobykina, O. V. Andreeva and M. G. Korochkina, Zh. Obshch. Khim., 2000, 70, 1406 (in Russian). 7 A. Altomare, G. Cascarano, C. Giacovazzo and D. Viterbo, Acta Crystallogr., 1991, A47, 744. 8 L. H. Straver and A. J. Schierbeek, MolEN. Structure Determination System. Program Description, Nonius B.V., 1994, vol. 1, p. 180. 9 A. L. Spek, Acta Crystallogr., 1990, A46, 34. 10 V. E. Kataev, in Konformatsionnyi analiz uglevodorodov i ikh proizvodnykh (Conformational Analysis of Hydrocarbons and Their Derivatives), ed. B. A. Arbuzov, Nauka, Moscow, 1990, p. 53 (in Russian). C(3B) C(2B) C(1B) C(4B) C(5B) C(6B) C(14B) C(13B) C(8B) C(15B) C(20B) C(16B) O(16B) C(17B) C(12B) C(19B) C(18B) O(1B) O(2B) C(21B) C(22A) C(22B) O(1) C(21A) O(1A) C(18A) O(2A) C(4A) C(19A) C(3A) C(20A) C(10A) C(2A) C(1A) C(9A) C(11A) C(12A) C(14A) C(15A) C(16A) C(13A) C(17A) O(16A) Figure 1 The crystal structure of bis-diterpene 3. Hydrogen atoms are omitted for clarity. C(10B) Received: 12th April 2000; Com. 00/16

ISSN:0959-9436     

出版商:RSC    

年代:2000

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) 2-Trifluoromethylperimidines with electron-withdrawing groups at the 6(7)-position: a case of extremely hindered annular prototropy Ekaterina A. Filatova,a Ivan V. Borovlev,b Alexander F. Pozharskii,*a Zoya A. Starikovac and Nikolay V. Vistorobskiia a Department of Chemistry, Rostov State University, 344090 Rostov-on-Don, Russian Federation.Fax:+7 8632 24 5905; e-mail: apozharskii@chimfak.rsu.ru b Department of Biology and Chemistry, Stavropol State University, 355009 Stavropol, Russian Federation. E-mail: nauka@stavsu.ru c A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 117813 Moscow, Russian Federation. Fax: +7 095 135 5085; e-mail: star@xrpent.ineos.ac.ru 10.1070/MC2000v010n05ABEH001328 In solutions of 6(7)-formyl-, 6(7)-acetyl- and 6(7)-p-toluenesulfonyl-2-trifluoromethylperimidines in non-polar solvents, both of the NH tautomers were detected using 1H NMR spectroscopy even on heating up to 130 °C.It is well known that annular tautomerism in NH azoles is a very fast process in the NMR time scale, which can be normally frozen only at rather low temperatures.1,2 Here, we report amidine-like NH heterocycles, in which annular prototropy is hindered so that distinct tautomers are observed not only under ordinary conditions but also on heating above 100 °C.We found that in the 1H NMR spectra of 6(7)-formyl-, 6(7)-acetyl- and 6(7)-p-toluenesulfonyl- 2-trifluoromethylperimidines† in non-polar solvents (CDCl3, CDCl2CDCl2 and C6D6) at room temperature all signals are duplicated showing the presence of both possible annular tautomers 1a–3a and 1b–3b [Figure 1(a)].‡ The individual tautomers can be easily identified by examining the multiplicity of signals for the 9-H proton adjacent to the pyrrole nitrogen atom.In all perimidines, this proton resonates at a considerably higher frequency in comparison with other aromatic protons.6 Thus, this signal for 6-R species 1a–3a is a doublet of doublets, whereas it looks as a doublet for 7-R species 1b–3b.Concentrations of each species and the tautomeric equilibrium constants KT = [a species]/[b species] were calculated from the relative intensities of corresponding peaks. It follows from Table 1 that the 7-R form somewhat dominates over the 6-R form for all compounds in non-polar media.We found by X-ray diffraction analysis of aldehyde 1 that the 7-R form is the only form in a solid state (Figure 2).§ The possible reason may consist in a much higher dipole moment of the 7-R form (m = 3.47 D) than that of † Compounds 1, 4 and 6 were prepared in accordance with procedures described in refs. 3, 4 and 5, respectively.New compounds 2 and 3 gave satisfactory elemental analyses. The synthesis of compounds 7 and 8 will be described elsewhere. The 1H NMR spectra were recorded on a Bruker-250 spectrometer. Because of fast prototropy in [2H6]DMSO, the atoms in compounds 1–3 were numbered arbitrarily. For 1: 1H NMR ([2H6]DMSO) d: 6.75 (br. d, 1H, 9-H), 7.03 (br. dd, 1H, 4-H), 7.55 (dd, 1H, 5-H, 3J5,4 7.9 Hz, 3J5,6 8.2 Hz), 7.85 (d, 1H, 8-H, 3J8,9 8.0 Hz), 8.64 (br.d, 1H, 6-H, 3J6,5 8.5 Hz), 9.89 (s, 1H, CHO), 12.40 (br. s, 1H, NH). For 1a: 1H NMR (CDCl3) d: 6.66 (dd, 1H, 9-H, 3J9,8 7.1 Hz, 4J9,7 0.7 Hz), 7.04 (d, 1H, 4-H, 3J4,5 7.8 Hz), 7.46 (dd, 1H, 8-H, 3J8,9 7.1 Hz, 3J8,7 8.9 Hz), 7.79 (d, 1H, 5-H, 3J5,4 7.8 Hz), 8.23 (br. s, 1H, NH), 8.77 (dd, 1H, 7-H, 3J7,8 8.9 Hz, 4J7,9 0.7 Hz), 10.04 (s, 1H, 6-CHO).For 1b: 1H NMR (CDCl3) d: 6.49 (d, 1H, 9-H, 3J9,8 7.9 Hz), 7.25 (dd, 1H, 4-H, 3J4,5 7.6 Hz, 4J4,6 0.7 Hz), 7.62 (dd, 1H, 5-H, 3J5,4 7.6 Hz, 3J5,6 8.7 Hz), 7.68 (d, 1H, 8-H, 3J8,9 7.9 Hz), 8.23 (br. s, 1H, NH), 8.82 (dd, 1H, 6-H, 3J6,5 8.7 Hz, 4J6,4 0.7 Hz), 9.97 (s, 1H, 7-CHO). For 2: A mixture of compound 4 (2 mmol), AcOH (3 mmol) and polyphosphoric acid (6 g, 84% P2O5) was stirred at 65 °C for 4 h and then poured into water (100 ml).The subsequent basification with NH4OH to pH 3–4, extraction with ethyl acetate (3×20 ml) and column chromatography on silica gel gave 2 (in the second fraction) as orange crystals with mp 218–219 °C (decane), 76% yield. 1H NMR ([2H6]DMSO) d: 2.57 (s, 3H, Me), 6.69 (br. d, 1H, 9-H, 3J9,8 8.0 Hz), 6.96 (br.dd, 1H, 4-H), 7.48 (dd, 1H, 5-H, 3J5,4 7.6 Hz, 3J5,6 8.7 Hz), 8.07 (d, 1H, 8-H, 3J8,9 8.1 Hz), 8.57 (br. dd, 1H, 6-H), 12.20 (br. s, 1H, NH). IR, (Vaseline oil, n/cm–1): 3180–3090 (NH), 1633 (C=O), 1613, 1580 (ring). For 2a: 1H NMR (CDCl3) d: 2.63 (s, 3H, Me), 6.55 (dd, 1H, 9-H, 3J9,8 7.6 Hz, 4J9,7 0.7 Hz), 6.92 (d, 1H, 4-H, 3J4,5 8.0 Hz), 7.35 (dd, 1H, 8-H, 3J8,7 8.9 Hz, 3J8,9 7.6 Hz), 7.92 (d, 1H, 5-H, 3J5,4 8.0 Hz), 8.10 (br.s, 1H, NH), 8.55 (dd, 1H, 7-H, 3J7,8 8.9 Hz, 4J7,9 0.7 Hz). For 2b: 1H NMR (CDCl3) d: 2.60 (s, 3H, Me), 6.35 (d, 1H, 9-H, 3J9,8 8.0 Hz), 7.16 (dd, 1H, 4-H, 3J4,5 7.5 Hz, 4J4,6 0.8 Hz), 7.52 (dd, 1H, 5-H, 3J5,4 7.5 Hz, 3J5,6 8.8 Hz), 7.83 (d, 1H, 8-H, 3J8,9 8.0 Hz), 8.10 (br. s, 1H, NH), 8.72 (dd, 1H, 6-H, 3J6,5 8.8 Hz, 4J6,4 0.8 Hz).For 3: A mixture of compound 4 (2 mmol), 4-MeC6H4SO3H·H2O (3 mmol) and polyphosphoric acid (5 g, 84% P2O5) was stirred at 140– 145 °C for 1 h and then poured into water (50 ml). The subsequent basification with NH4OH to pH 4–5 gave a solid, which was filtered off, washed with water and dried. After column chromatography on silica gel, firstly, with benzene to separate 4(9)-p-toluenesulfonyl-2-trifluoromethylperimidine (14%, yellowish crystals, mp 253–254 °C) and then with benzene–ethyl acetate (10:1) gave 3 as yellow-green crystals with ‡ Preliminary 19F and 13C NMR examinations of compounds 1–3 led to the same conclusions.mp 259–260 °C (benzene), 44% yield. 1H NMR ([2H6]DMSO) d: 2.33 (s, 3H, Me), 6.80 (br. d, 1H, 9-H), 6.97 (br.dd, 1H, 4-H), 7.37 (d, 2H, 4-MeC6H4SO2, 3'-H and 5'-H, J0 8.1 Hz), 7.46 (br. dd, 1H, 5-H), 7.77 (m, 3H, 6-H, 4-MeC6H4SO2, 2'-H and 6'-H, J0 8.1 Hz), 8.14 (d, 1H, 8-H, 3J8,9 8.9 Hz), 12.30 (br. s, 1H, NH). For 3a: 1H NMR (CDCl3) d: 2.35 (s, 3H, Me), 6.53 (dd, 1H, 9-H, 3J9,8 7.3 Hz, 4J9,7 0.7 Hz), 6.99 (d, 1H, 4-H, 3J4,5 7.8 Hz), 7.22 (d, 2H, 4-MeC6H4SO2, 3'-H and 5'-H, J0 8.4 Hz), 7.25 (m, 1H, 8-H), 7.78 (d, 2H, 4-MeC6H4SO2, 2'-H and 6'-H, J0 8.4 Hz), 7.85 (dd, 1H, 7-H, 3J8,9 8.7 Hz), 8.26 (d, 1H, 5-H, 3J5,4 7.8 Hz), 8.43 (br.s, 1H, NH). For 3b: 1H NMR (CDCl3) d: 2.35 (s, 3H, Me), 6.45 (d, 1H, 9-H, 3J9,8 8.1 Hz), 7.07 (dd, 1H, 4-H, 3J4,5 7.5 Hz, 4J4,6 0.7 Hz), 7.21 (d, 2H, 4-MeC6H4SO2, 3'-H and 5'-H, J0 8.4 Hz), 7.40 (dd, 1H, 5-H, 3J5,4 7.5 Hz, 3J5,6 8.7 Hz), 7.77 (d, 2H, 4-MeC6H4SO2, 2'-H and 6'-H, J0 8.4 Hz), 7.90 (dd, 1H, 6-H, 3J6,5 8.7 Hz, 4J6,4 0.7 Hz), 8.13 (d, 1H, 8-H, 3J8,9 8.1 Hz), 8.60 (br.s, 1H, NH). NH N R1 R2 N NH R1 R2 4 5 6 7 8 9 4 5 6 7 8 9 1a–6a 1b–6b 1 R1 = CF3, R2 = CHO 2 R1 = CF3, R2 = COMe 3 R1 = CF3, R2 = 4-MeC6H4SO2 4 R1 = CF3, R2 = H 5 R1 = Me, R2 = H 6 R1 = H, R2 = COMe NMe N CF3 7a,b O R NMe N CF3 8a,b R O 7, 8: a R = H b R = MeMendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) its 6-R counterpart (m = 1.05D).¶ This can result in more effective stabilisation of the 7-R form in a crystalline state and, to a certain extent, in solution because of stronger dipole–dipole interactions. We failed to reach a coalescence temperature for signals of both of the tautomeric forms in the non-polar solvents used.Upon heating a solution of aldehyde 1 or ketone 2 in C6D6 up to 70 °C or in CDCl2CDCl2 up to 130 °C, only slight broadening of the indicator peaks was observed. Judging from these observations, we can suggest that the value of DG� for the tautomerisation of compounds 1 and 2 in non-polar media may be higher than 20 kcal mol–1. To the best of our knowledge, this is an unprecedentedly high value for annular tautomerism in azole systems (cf.refs. 1 and 2). At the same time, the coalescence does occur when a drop of D2O is added to a solution of 1–3 in CDCl2CDCl2.†† Moreove fast tautomerisation with averaging signals of both of the forms takes place at room temperature in solutions of 1–3 in polar solvents, e.g., CD3CN and [2H6]DMSO [Figure 1(b)].In this instance, the percentage of tautomers in an equilibrium mixture was calculated for compounds 1 and 2 using the equation8 where pt is the difference between the chemical shifts of 4-H and 9-H atoms for compound 1 or 2, p7 and p8 are the analogous differences for fixed forms 7 and 8 (Table 2), ca and cb are the molar fractions of tautomers 1a,2a and 1b,2b, respectively.As can be seen in Table 1, the ratio between both of the forms for aldehyde 1 and ketone 2 in non-polar and polar solvents differs little; the only exception is compound 2 in CD3CN, for which the 6-COR form becomes somewhat predominant. A pronounced influence of perfluoroalkyl groups on prototropy in NH-containing heterocycles was reported.9 In 2-perfluoropropylimidazole, a stabilisation of annular prototropy was observed as thought because of intramolecular hydrogen bonding between NH protons and terminal fluorine atoms in the n-C3F7 substituent. 10 Obviously, a similar explanation is not valid in our case because (i) no stabilisation of prototropy was noticed for 2-CF3- and 2-C2F5-imidazoles10 and (ii) X-ray diffraction data did not indicate the existence of similar intramolecular hydrogen bonding for 1.We believe that the main reason for the very slow tautomerism of compounds 1–3 in non-polar media consists in their very low basicity‡‡ and insufficient NH acidity to ensure fast proton interchange between different molecules of the hetero- § Crystals of 1 suitable for X-ray analysis were obtained by slow evaporation of a solution of 1 in acetylacetone.A red single crystal (0.50× ×0.25×0.20 mm) containing 0.5 molecules of acetylacetone per molecule of 1 was chosen (C13H7F3N2O·0.5C5H8O2, M = 314.26). The crystals are orthorhombic, a = 6.9420(14) Å, b = 16340(3) Å, c = 24.776(5) Å, V = 2810.4(10) Å3, dcalc = 1.485 g cm–3, Z = 8, space group Pmc21, m(MoKa) = 1.26 cm–1, F(000) = 1288.Intensities of 3645 reflections were measured on an Enraf-Nonius CAD4 diffractometer at 293 K (graphite-monochromated MoKa radiation, q\5/3q scan technique, q £ £26.96°) and 3306 independent reflections (Rint = 0.0518) were used in further calculations and refinement. The structure was solved by a direct method and refined by a full-matrix least-squares technique against F2 in an anisotropic approximation for non-hydrogen atoms.All hydrogen atoms were placed in the geometrically calculated positions and included in the refinement using the riding model approximation with Uiso(H) = 1.5Ueq(Ci) and Uiso(H) = 1.2Ueq(Cj), where Ci and Cj are the carbon atoms to which the corresponding hydrogen atoms are attached in methyl groups and benzene rings, respectively.The refinement was converged to wR2 = = 0.1515 and GOOF = 0.936 for all independent reflections [R1 = 0.0438 is calculated against F for the 1183 independent reflections with I > 2s(I)]. The number of the refined parameters was 547. All calculations were performed using SHELXTL PLUS 5.0 on an IBM computer. 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., Issue 1, 2000. Any request to the CCDC for data should quote the full literature citation and the reference number 1135/67. ¶ The dipole moments were calculated by the PM3 method for conformations in which a carbonyl oxygen atom is directed towards the periproton.The occurrence of such conformations was confirmed by X-ray diffraction data (for 1) and 1H NMR spectra showing strong deshielding of peri-protons for both of the tautomers. Table 1 Ratio between tautomers at 25 °C. Compound Solvent Content (%) Equilibrium constant 6-COR (1a–3a) 7-COR (1b–3b) 1 CDCl3 37 63 0.59 CDCl2CDCl2 34 66 0.52 C6D6 38 62 0.62 [2H6]DMSO 33a aFast equilibrium. 67a 0.50a CD3CN 38a 62a 0.61a 2 CDCl3 40 60 0.67 CDCl2CDCl2 38 62 0.61 C6D6 47 53 0.89 [2H6]DMSO 49a 51a 0.96a CD3CN 68a 32a 2.12a 3 CDCl3 33 67 0.49 CDCl2CDCl2 36 64 0.56 KT = [form a] [form b] pt = cap7 + cbp8, (1) ††Unlike 1 and 2, prototropy in 3 is extremely sensitive to moisture traces. Thus, in three different commercial batches of CDCl3, only the average spectrum of 3 was observed, whereas in each of these cases compounds 1 and 2 demonstrated separate signals of both tautomers. Tautomers 3a and 3b could be observed only in a carefully dried sample of CDCl3.Indirectly, these data indicate that the tautomerisation of 1–3 most likely proceeds through a mesomeric N anion rather than the perimidinium cation. Indeed, the NH acidity of 3 should be greater than that of 1 and 2 because the 4-MeC6H4SO2 group (sp = 0.67) is a stronger electron acceptor than CHO (sp = 0.22) and COMe (sp = 0.50).7 ‡‡ In accordance with published data,11 the value of pKa for 1-methyl-2- trifluoromethylperimidine in MeCN is equal to 6.64. Extrapolation to an aqueous solution results in pKa within the limits from –1.0 to –0.5.Obviously, the basicity of compounds 1–3 should be even lower. 9.0 8.0 7.0 6.0 d/ppm Figure 1 1H NMR spectra (250 MHz, 30 °C) of compound 2 in (a) CDCl3 and (b) [2H6]DMSO. (a) (b) 2b 2a NH 2a 2b 2a 2b 2b 2a 2a 2b F(1') F(2'A) H(1'A) C(2') F(2') N(1') C(1') N(2') C(4') C(3') C(11') C(12') C(5') C(6') C(7') C(10') H(13C) C(13') C(8') C(9') O(1') Figure 2 Molecular structure of compound 1 (one of four independent molecules is shown; the acetylacetone molecule is omitted for clarity; the atom numbering does not correspond to the IUPAC nomenclature).Selected bond lengths and distances (Å): N(1')–C(1') 1.39(2), N(2')–C(1') 1.29(2), N(1')–C(3') 1.34(2), N(2')–C(11') 1.40(2), C(6')–C(13') 1.45(2), O(1')– C(13') 1.27(2), O(1')···H(8'A) 2.38(0.02), O(1')···C(8') 3.00(0.02); selected bond angles (°): C(3')–N(1')–C(1') 115(1), C(1')–N(2')–C(11') 116(1), N(2')–C(1')–N(1') 127(1), N(2')–C(1')–C(2') 119(1), N(1')–C(1')–C(2') 113(1), N(1')–C(3')–C(12') 123(1), N(1')–C(3')–C(4') 117(1), C(5')–C(6')– C(13') 112(1), C(6')–C(7')–C(8') 121(1), O(1')–C(13')–C(6') 124(2).Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) cyclic compounds (conjugated cations or anions are known to be ordinary prototropy intermediates in NH heterocycles).1 This view is substantiated by the fact that 2-trifluoromethyl- and 2-methylperimidines 4 and 5, respectively, as well as 6(7)-acetylperimidine 6, exhibit only average spectra even in non-polar solvents (see also ref. 12).§§ It follows from the above discussion that the specificity of compounds 1–3 consists in a cooperative electron acceptor effect of the 2-CF3 group and a substituent at the 6(7)-position, which creates an optimal balance of the basicity and NH acidity making prototropy in non-polar media extremely hindered.References 1 J. Elguero, C. Marzin, A. R. Katritzky and P. Linda, The Tautomerism of Heterocycles, Adv. Heterocycl. Chem., Supplement 1, Academic Press, New York, 1976. 2 V. I. Minkin, A. D. Garnovskii, J. Elguero, A. R. Katritzky and O. V. Denisko, Adv. Heterocycl. Chem., 2000, 76, 157. 3 A. F. Pozharskii, E. A. Filatova, N. V. Vistorobskii and I. V. Borovlev, Khim. Geterotsikl. Soedin., 1999, 365 [Chem. Heterocycl. Compd. (Engl. Transl.), 1999, 35, 319]. 4 A. F. Pozharskii, G. G. Yurchuk and L. L. Gervits, Khim. Geterotsikl. Soedin., 1979, 413 [Chem.Heterocycl. Compd. (Engl. Transl.), 1979, 15, 342]. 5 A. F. Pozharskii, I. V. Borovlev and I. S. Kashparov, Khim. Geterotsikl. Soedin., 1975, 543 [Chem. Heterocycl. Compd. (Engl. Transl.), 1975, 11, 480]. 6 A. F. Pozharskii and V. V. Dal’nikovskaya, Usp. Khim., 1981, 50, 1559 (Russ. Chem. Rev., 1981, 50, 816). 7 A. J. Gordon and R. A. Ford, The Chemist’s Companion, Wiley- Interscience, New York, 1972. 8 D. S. Wofford, D. M. Forkey and J. G. Russell, J. Org. Chem., 1982, 47, 5132. 9 J. Elguero, A. Fruchier, N. Jagerovic and A. Werner, Org. Prep. Proced. Int., 1995, 27, 33. 10 H. Kimoto, S. Fojii and L. A. Cohen, J. Org. Chem., 1982, 47, 2867. 11 A. F. Pozharskii and G. G. Yurchuk, Khim. Geterotsikl. Soedin., 1979, 418 [Chem. Heterocycl. Compd. (Engl. Transl.), 1979, 15, 346]. 12 P. D. Woodgate, J. M. Herbert and W. A. Denny, Magn. Reson. Chem., 1988, 26, 191. §§ It is noteworthy that in compound 4, unlike 5, the average 4-H and 9-H signal is considerably broadened even at room temperature. Thus, the 2-CF3 group alone slows down prototropy, though to a lesser extent than both substituents in compounds 1–3. Table 2 Chemical shifts of 4-H and 9-H protons in polar solvents. Compound Solvent d(9-H)a/ ppm aThe atom numbering in compounds 1 and 2 is arbitrary. d(4-H)a/ ppm p = d(4-H) – d(9-H)/ ppm 1 [2H6]DMSO 6.75 7.03 0.28 CD3CN 6.75 7.05 0.30 2 [2H6]DMSO 6.69 6.96 0.27 CD3CN 6.65 6.95 0.30 7a [2H6]DMSO 7.00 7.04 0.04 CD3CN 6.85 7.00 0.15 7b [2H6]DMSO 6.88 6.95 0.07 CD3CN 6.76 6.93 0.17 8a [2H6]DMSO 6.83 7.23 0.40 CD3CN 6.65 7.20 0.55 8b [2H6]DMSO 6.68 7.14 0.46 CD3CN 6.55 7.13 0.58 Received: 19th May 2000; Com. 00/1654

ISSN:0959-9436     

出版商:RSC    

年代:2000

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) Synthesis and reactivity of 4-lithium and 4-copper derivatives of sydnone imines Ilya A. Cherepanov and Valery N. Kalinin* A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 117813 Moscow, Russian Federation. Fax: +7 095 135 5085; e-mail: vkalin@ineos.ac.ru 10.1070/MC2000v010n05ABEH001319 4-Lithium and 4-copper sydnone imines have been obtained, and preparative methods for the direct introduction of hydroxyalkyl, acyl, carbalkoxyl, vinyl and aryl groups into the 4-position of sydnone imines have been developed on this basis.Sydnone imines 1 and their exocyclic N6-derivatives 2 hold a special place among mesoionic heterocycles.1–4 This unique class of synthetic compounds has no analogues among the known natural substances.Sydnone imines exhibit biological activity,2,4 and a number of medicines were created on this basis. The cyclization of substituted N-nitroso-a-aminonitriles in acid media is the most productive method for the preparation of sydnone imines. However, this method has a significant drawback because the necessary a-aminonitriles are not easily accessible, and their functional groups may hinder the cyclization. The direct introduction of substituents into the already formed sydnone imine ring using organometallic derivatives can solve the problem of the direct synthesis of sydnone imines.Unfortunately, only 4-mercurio sydnone imines obtained by the direct mercuration of sydnone imines are presently known.5 However, these compounds found no synthetic applications.All attempts to obtain lithium derivatives of sydnone imines by the replacement of bromine with lithium in 4-bromo-N6- acetyl sydnone imines by analogy with sydnones were unsuccessful. 6 In this study, we developed a method for the direct functionalization of sydnone imines using their organometallic derivatives.We supposed that 4-lithium-N6-acyl derivatives of sydnone imines can be synthesised by the direct metallation of sydnone imines unsubstituted at the 4-position in the presence of butyllithium: The following two side reactions can occur in the synthesis of 4-lithium-N6-acyl derivatives of sydnone imines by this method: the addition of a metallation agent to the carbonyl group and decomposition of the obtained lithium derivatives.In our opinion, the carbonyl activity in N6-acyl derivatives of sydnone imines is essentially suppressed because of a high negative charge of the exocyclic nitrogen. The influence of the latter side reaction is significant only in the case of low-reactivity electrophiles, when the rate of the reaction of 4-lithium derivatives with electrophiles is comparable to the rate of decomposition.The reaction mixture changed from colourless to yellow-brown within 30 min on the treatment of 3-cyclohexyl-N6-pivaloyl sydnone imine in THF with BunLi at –78 °C. The solution became light yellow on the addition of benzaldehyde. The treatment of the reaction mixture with water followed by chromatography resulted in the formation of an alcohol (53% yield) as a product of addition of 4-lithium sydnone imine to benzaldehyde.We found that the metallation of other sydnone imines can also be performed, and other substrates that react with lithium sydnone imines can be used (Table 1).† Unfortunately, 4-lithium sydnone imine derivatives exhibit low nucleophilicity and are thermally unstable. At –78 °C, these derivatives do not react with active electrophiles such as trimethylsilyl chloride, methyl iodide and allyl bromide, and they decompose at higher temperatures.Carbonyl compounds that are incapable of enolization were N N O R R' NH2 X N N O R R' N O R'' 1 2 R = alkyl, aryl, NR2 R' = H, alkyl, aryl, alkenyl, alkynyl R'' = alkyl, aryl, OR, NR2 Table 1 Reactivity of 4-lithium derivatives of sydnone imines.Run R1 R2 E+ E Yield (%) mp/°C 1 cyclo-C6H11 ButC(O) PhCHO PhCH(OH) 53 168–169 2 cyclo-C6H11 ButC(O) p-ClC6H4CHO p-ClC6H4CH(OH) 63 185 (decomp.) 3 cyclo-C6H11 ButC(O) 53 130–132 4 cyclo-C6H11 ButC(O) 33 134 (decomp.) 5 cyclo-C6H11 ButC(O) AcOCl MeOC(O) 83 70–71 6 cyclo-C6H11 PhC(O) PhCHO PhCH(OH) 45 173–175 7 cyclo-C6H11 CF3C(O) PhCHO PhCH(OH) 47 118–120 8 cyclo-C6H11 MeC(O) PhCHO PhCH(OH) 30 137 (decomp.) 9 cyclo-C6H11 MeOC(O) PhCHO PhCH(OH) 65 142–144 10 cyclo-C6H11 p-MeC6H4SO2 PhCHO PhCH(OH) 44 160–161 11 1-morpholine PhC(O) PhCHO PhCH(OH) 62 181–182 12 1-morpholine PhC(O) AcOCl MeOC(O) 60 124–125 13 1-morpholine PhC(O) CH2O HOCH2 36 147–149 N N O R1 H N R2 N N O R1 Li N R2 BunLi, THF –78 °C, 30 min E+ N N O R1 E N R2 O CHO O CH(OH) O CHO I O CH(OH) I N N O R1 H N R2 BunLi N N O R1 Li N R2Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) found to be the only type of electrophiles that react with 4-lithium sydnone imines. The low stability of 4-lithium sydnone imines and a small number of electrophiles that react with 4-lithium derivatives significantly restrict the preparative capabilities of using 4-lithium sydnone imines for the direct functionalization of a sydnone imine ring. 4-Copper sydnones, which are oxygen analogues of sydnone imines, are known to be highly stable. Convenient preparative methods for introducing different substituents at the 4-position of sydnones via palladium-catalysed cross-coupling reactions were developed for 4-copper sydnones.7,8 We suppose that 4-copper sydnone imines are as stable as the sydnones.On the addition of copper bromide (1 equiv.) to a solution of 4-lithium-3-cyclohexyl-N6-pivaloyl sydnone imine at –78 °C, the colour of the reaction mixture became deeper, and copper bromide underwent dissolution. This suggests the formation of 4-copper sydnone imines. An increase in the temperature to room temperature and even the refluxing of the solution for several hours did not result in decomposition of 4-copper sydnone imine.We also examined the applicability of 4-copper derivatives to palladium-catalysed cross-coupling reactions with different organohalides (Table 2).‡ Preparative methods for the direct introduction of hydroxyalkyl, acyl, carbalkoxyl, vinyl, and aryl groups at the 4-position of a sydnone imine ring were developed on the basis of the synthesised organometallics. This work was supported by the Russian Foundation for Basic Research (grant no. 93-03-33107). References 1 H. U. Daeniker and J. Druey, Helv. Chim. Acta, 1962, 45, 2426. 2 V. G. Yashunskii and L. E. Kholodov, Usp. Khim., 1980, 49, 54 (Russ. Chem. Rev., 1980, 49, 28). 3 L. B. Clapp, in Comprehensive Heterocyclic Chemistry, ed.K. T. Potts, Pergamon Press, Oxford, 1984, vol. 6, p. 365. 4 C. G. Newton and C. A. Ramsden, Tetrahedron, 1982, 38, 2967. 5 H. Kato, M. Hashimoto and M. Otha, Nippon Kagaku Zasshi, 1957, 78, 707. 6 S. A. Zotova and V. G. Yashunskii, Zh. Org. Khim., 1965, 1, 2218 [J. Org. Chem. USSR (Engl. Transl.), 1965, 1, 2258]. 7 V. N. Kalinin and F. M. She, J. Organomet. Chem., 1988, 352, C34. 8 V. N. Kalinin, D. N. Pashchenko and F. M. She, Mendeleev Commun., 1992, 60. † Typical experimental procedure. A solution of BunLi (2.1 mmol) in hexane was added to a solution of sydnone imine (2.0 mmol) in 50 ml of absolute THF at –78 °C. The mixture was stirred at –78 °C for 30 min; then, 3.0 mmol of an electrophile was added. After the mixture was heated to room temperature, 1 ml of water was added, the mixture was diluted with 100 ml of methylene chloride and filtered through a layer of Al2O3.The solvent was removed by evaporation, and the residue was chromatographed on SiO2 (chloroform–diethyl ether, 10:1). The resulting product was crystallised from diethyl ether–hexane. Satisfactory elemental analysis and 1H NMR data were obtained for all substances.Table 2 Reactivity of 4-copper derivatives of sydnone imines. Entry R1 R2 R3Hal Yield (%) mp/°C 1 cyclo-C6H11 ButC(O) PhCH=CHBr 53 206 (decomp.) 2 cyclo-C6H11 CF3C(O) PhI 63 156–158 3 cyclo-C6H11 CF3C(O) PhCH=CHBr 53 199 (decomp.) 4 cyclo-C6H11 CF3C(O) MeCOCl 33 92–93 5 cyclo-C6H11 CF3C(O) PhCOCl 30 150–151 6 Me ButC(O) p-O2NC6H4I 45 132–133 7 Me ButC(O) CH2=CHBr 65 92–94 8 Me ButC(O) PhCH=CHBr 47 210 (decomp.) 9 Me CF3 C (O) PhCH=CHBr 44 200–201 N N O R1 H N R2 N N O R1 Cu N R2 i, BunLi, THF –78 °C, 30 min R3Hal N N O R1 R3 N R2 ii, CuBr, –78 ® 20 °C Pd(PPh3)4 20 °C, 2–24 h ‡ Typical experimental procedure. A solution of BunLi (2.1 mmol) in hexane was added to a solution of sydnone imine (2.0 mmol) in 50 ml of absolute THF at –78 °C.The mixture was stirred at –78 °C for 30 min; then, 2.1 mmol of copper(I) bromide was added. The mixture was additionally stirred for 20 min. After the mixture was heated to room temperature, 3.0 mmol of an organohalide and 0.1 mmol of tetrakis-triphenylphosphinepalladium( 0) were added. The mixture was stirred for 2–24 h until the reaction completed (monitoring by TLC). The reaction mixture was decomposed with water, then diluted with 100 ml of methylene chloride and filtered through a layer of Al2O3. The solvent was removed by evaporation, and the residue was chromatographed on SiO2 (chloroform– diethyl ether, 10:1). The resulting product was crystallised from diethyl ether–hexane. Satisfactory elemental analysis and 1H NMR data were obtained for all substances. Received: 27th April 2000; Com. 00/1645

ISSN:0959-9436     

出版商:RSC    

年代:2000

数据来源: RSC

摘要:

Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) Effective synthesis of 1,2-di-, 1,2,3-tri-, 1,2,3,3-tetraalkyldiaziridines and 1,5-diazabicyclo[3.1.0]hexanes Nina N. Makhova,* Anatolii N. Mikhailyuk, Vladimir V. Kuznetsov, Sergei A. Kutepov and Pavel A. Belyakov N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow, Russian Federation. Fax: +7 095 135 5328; e-mail: mnn@cacr.ioc.ac.ru 10.1070/MC2000v010n05ABEH001350 A versatile single-step procedure was proposed for the synthesis of the title compounds by the interaction of equimolar amounts of aliphatic carbonyl compounds, primary aliphatic amines and N-chloroalkylamines in an aprotic organic solvent in the presence of potassium carbonate.A number of methods for the synthesis of 1,2-dialkyldiaziridine derivatives are known,1–5 depending on substituents at the 3-position of the ring.Thus, a synthesis of 1,2-dialkyl- and 1,2,3- trialkyldiaziridines is based on the interaction of 1 mol of an aldehyde and 2 mol of a primary aliphatic amine with NaOCl in an aqueous alkaline medium1 under controlled pH.2,3 However, methods based on reactions in water cannot be extended to the production of 1,2,3,3-tetraalkyldiaziridines and diaziridines from sterically hindered and water-insoluble amines.A few tetrasubstituted diaziridines were earlier prepared by transformations of 1-H- or 1,2-H-diaziridines.6,7 At the same time, diaziridine derivatives are convenient compounds for studying the stereochemistry of nitrogen,8 in particular, for spontaneous resolution into enantiomers. 9 We synthesised10 sterically hindered 1,2-di(1-adamantyl)diaziridine, which cannot be prepared using the above methods, by the interaction of 1 mol of ButOCl with a mixture of 1 mol of formaldehyde and 2 mol of 1-aminoadamantane in CHCl3 in the presence of K2CO3 as a base. On this basis, we hoped to develop a versatile single-step method for the preparation of 1,2-di-, 1,2,3-tri- and 1,2,3,3-tetraalkyldiaziridines.For this purpose, we examined the reaction of carbonyl compounds, primary aliphatic amines and N-chloroalkylamines in aprotic organic solvents in the presence of K2CO3. It is well known11 that, regardless of the synthetic procedure, the diaziridine ring is closed by intramolecular nucleophilic substitution in a methylenediamine intermediate 2, which contains a readily leaving group (Hal, HSO4 or OSO2R) at a nitrogen atom.Intermediate 2 can be formed from an amine and a carbonyl compound via a-aminocarbinol 1 followed by the a-aminomethylation of an N-chloroalkylamine (Scheme 1). The cyclization of 2 to diaziridine 3 is rapid; because of this, the formation of 2 is the rate-limiting step in the synthesis of diaziridines.Successful formation of 2 in aqueous solution was optimised by adjusting the pH.2,3 In an aprotic medium, the dehydration of 1 to form imines 4 and methylenebisamines 5 may be an alternative pathway of the reaction. In the case of aldehydes, and in particular, formaldehyde, trimerisation of 4 to hexahydro-1,3,5-triazines 6 can also occur.In principle, compounds 5, as well as a-aminocarbinol 1, can give diaziridines in the reaction with N-chloroalkylamines. However, it is likely that this reaction pathway is hindered in an aprotic medium (Scheme 1). a-Aminocarbinols of aliphatic amines are unstable under ordinary conditions. In particular, N-piperidinocarbinol was isolated and characterised by spectroscopy at a low temperature; however, it transformed into methylenebispiperidine with increasing temperature.12 Stable a-aminocarbinols were obtained from only amines or carbonyl compounds that bear electron-acceptor substituents. 13,14 Hydroxymethyl derivatives of diaziridines15 and aziridines16 were also described. There is no published data on the stability of a-aminocarbinols 1 in aprotic organic solvents over long time.Thus, before attempting to synthesise diaziridines in the presence of K2CO3, we examined the behaviour of the reaction mixture (in both the absence and presence of K2CO3) obtained by passing gaseous formaldehyde into a solution of allylamine in CD2Cl2 at –30 °C by 1H NMR spectroscopy. The 1H NMR spectra† of parent allylamine and 1,3,5-triallylhexahydro-1,3,5- triazine 6a17 were measured under the same conditions.The spectrum measured immediately after mixing allylamine and formaldehyde at –30 °C exhibited the signals of allylamine† and two groups of signals with the 4:1 ratio between the integrated intensities, which can be attributed, by analogy with published data,15,16 to a CH2 group of a-aminocarbinol 1a (s, 4.4 ppm) and an NCH2N group (3.47 ppm) of methylenediamine 5a.Next, the ampoule was heated to 20 °C and after holding for 1 min cooled again to –30 °C. In the 1H NMR spectrum of this solution, the above signals were retained; however, the ratio between the integrated intensities was 1:1, and weak signals of hexahydrotriazine 6a appeared. After holding this ampoule at 20 °C for 10 min, almost pure compound 6a was detected in solution; that is, hexahydrotriazine 6a is the end product of the reaction even after a short time under the conditions specified.A completely different behaviour was observed when an equimolar amount of K2CO3 was added to an analogous reaction mixture prepared at –30 °C. After stirring at 20 °C for 10 min, the reaction mixture was cooled to –30 °C, potassium carbonate † All new compounds exhibited satisfactory elemental analyses, and their structures were confirmed by IR, 1H and 13C NMR spectroscopy. The IR spectra were measured on an UR-20 spectrometer in thin films of pure substances; 1H and 13C NMR spectra were recorded on Bruker WM-250 (250 MHz) and Bruker AM-300 (75.5 MHz) spectrometers, respectively (TMS was used as an internal standard). 1,2-Dimethyl- (3b),1 1,2-bis(2- acetamidoethyl)- (3c),2 1,2,3-trimethyl- (3f)2 and 1,2-dibutyl-3-methyl- (3g)22 diaziridines as well as 1,5-diazabicyclo[3.1.0]hexane 7a18 and its 3-methyl (7b)18 and 3,3-dimethyl (7c)18 derivatives were described in the literature. 1,3,5-Triallylhexahydro-1,3,5-triazine 6a: 1H NMR (CD2Cl2, –30 °C) d: 2.65, 3.65 (AB system, 2H, NCH2N, 2J 13 Hz), 2.95 (d, 2H, NCH2, 3J 8 Hz), 5.05 (m, 2H, =CH2), 5.67 (m, 1H, =CH).Allylamine: 1H NMR (CD2Cl2, –30 °C) d: 1.6 (br. s, 2H, NH2), 3.15 (dq, 2H, NCH2, 3J 6 Hz and 2 Hz), 4.95 (m, 2H, =CH2), 5.85 (m, 1H, =CH). N-Hydroxymethylallylamine 1a: 1H NMR (CD2Cl2, –30 °C) d: 3.5 (d, 2H, NCH2C=), 4.4 (s, 2H, NCH2O), 5.2 (m, 2H, CH2=), 6.9 (m, 1H, CH=). O R R1 + R2NH2 OH NHR2 R1 R R3NHCl NR3 NHR2 R1 R Cl N N R2 R R1 R3 N N N R1 R2 R2 R2 R1 R1 R1RC NR2 R2NHC(R,R1)NHR2 6 a R = R1 = H, R2 = R3 = CH2CH=CH2 R2NH2 1 2 3 5 4 – H2O R3NHCl – R2NH2 K2CO3 Scheme 1 R R RMendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) was filtered off, and the 1H NMR spectrum of the resulting solution was measured. All operations were performed at –30 °C. a-Aminocarbinol 1a† was found to be the main component of this reaction mixture.Moreover, after stirring at 20 °C with K2CO3 for 1 h followed by the removal of K2CO3, the shape of the 1H NMR spectrum at –30 °C was changed only slightly. Although signals of 5a appeared, 1a was the major product. Hexahydrotriazine 6a was almost completely absent from this mixture. Thus, we found that the a-aminocarbinol prepared from a primary aliphatic amine and formaldehyde can be retained in an aprotic organic solvent containing K2CO3 for a reasonably long time without conversion into hexahydro-1,3,5-triazine.It is likely that potassium carbonate, which exhibits both basic and dehydrating properties, can remove trace water from an aprotic medium (under these conditions, water can play a role of a weak acid) and result in the stabilisation of the a-aminocarbinol.However, to perform the reaction successfully, the reaction mixture should be continuously efficiently stirred; when the stirring was stopped, a water layer appeared after several minutes, and hexahydrotriazine was formed. Based on these results, we examined the synthesis of diaziridines from carbonyl compounds, primary aliphatic amines and N-chloroalkylamines in aprotic organic solvents in the presence of potassium carbonate.‡ Formaldehyde, acetaldehyde, acetone, methyl ethyl ketone and acetamidoacetone (a ketone with an electron-acceptor group) were taken as carbonyl compounds.Of primary amines, methylamine, allylamine, 2-hydroxyethylamine and 2-acetamidoethylamine (the two amines last named bear electron-acceptor substituents) were examined.For the reason of an amine and an N-chloroalkylamine with different alkyl groups, the N-chloroalkylamine was prepared by the reaction of the corresponding amine (as a rule, MeNH2) with NaOCl followed by extraction with methylene chloride or chloroform, which were also used as the reaction solvent. In the case of an amine and an N-chloroalkylamine with identical alkyl groups, the N-chloroalkylamine was prepared by the reaction between 1 mol of BuOCl and 2 mol of the corresponding amine in the above solvents.The organic reactants were taken in equimolar amounts, and potassium carbonate was taken in a threefold amount (Scheme 2).§ The reaction was complete after 8–10 h in 30–70% yields.The optimum reaction temperature was 20–22 °C in the case of alkyl-substituted amines and carbonyl compounds or 24–26 °C for those bearing electron-acceptor substituents. This procedure was extended to other compounds. Thus, a series of 1,5-diazabicyclo[3.1.0]hexanes† 7 was prepared in high yields from equimolar amounts of corresponding carbonyl compounds, 1,3-diaminopropane and ButOCl in the presence of K2CO3 (Scheme 3).‡,§ It was found previously18–21 using 1H and 13C NMR spectroscopy and X-ray diffraction data that compounds 7a–c predominantly occur in the boat conformation, and the introduction of an endo-Me group results in flattering the ring.A comparison of the chemical shifts of the carbon atoms and the spin–spin coupling constants of the protons on the pyrazolidine ring of previously unknown compound 7d with the corresponding values for 7b,c suggests that it also contains a flattened boat conformation with methyl and acetamidomethyl groups in the endo and exo positions, respectively.This work was supported by the Russian Foundation for Basic Research (grant no. 97-03-33021a) and INTAS (grant no. 99- 0157). References 1 R.Ohme, E. Schmitz and P. Dolge, Chem. Ber., 1966, 99, 2104. 2 V. V. Kuznetsov, N. N. Makhova, Yu. A. Strelenko and L. I. Khmel’nitskii, Izv. Akad. Nauk SSSR, Ser. Khim., 1991, 2861 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1991, 40, 2496). 3 V. V. Kuznetsov, N. N. Makhova and L. I. Khmel’nitskii, Izv. Akad. Nauk, Ser. Khim., 1997, 1410 (Russ. Chem. Bull., 1997, 46, 1354). 4 E.Schmitz and D. Habisch, Chem. Ber., 1962, 95, 680. 5 E. Schmitz and K. Schinkowski, Chem. Ber., 1964, 97, 49. 6 R. G. Kostyanovsky, G. V. Shustov and O. L. Nabiev, Khim.-Farm. Zh., 1986, 20, 671 (in Russian). 7 N. N. Makhova, G. A. Karpov, A. N. Mikhailyuk and L. I. Khmel’nitskii, Mendeleev Commun., 1999, 112. 8 G. V. Shustov, A. I. Prokof’ev, S. N. Denisenko, A. Yu. Shibaev, Yu. V.Pusanov and R. G. Kostyanovsky, J. Chem. Soc., Perkin Trans. 2, 1990, 141. 9 R. G. Kostyanovsky, K. A. Lyssenko and V. R. Kostyanovsky, Mendeleev Commun., 2000, 44. 10 N. N. Makhova, V. V. Kuznetsov and R. G. Kostyanovsky, Izv. Akad. Nauk, Ser. Khim., 1996, 1870 (Russ. Chem. Bull., 1996, 45, 1780). 11 H. W. Heine, in Chemistry of Heterocyclic Compounds, ed. A. Hassner, Wiley-Interscience, New York, 1983, vol. 42, part 2, p. 547. 12 R. G. Kostyanovsky and O. A. Pan’shin, Izv. Akad. Nauk SSSR, Otdel. Khim. Nauk, 1963, 182 (in Russian). O R R1 + R2NH2 + R3NHCl N N R2 R R1 R3 3 K2CO3 Scheme 2 a bc def g hi j kl mn H H H H H H H Me Me Me Me Me Me Me H H H H H Me Me Me Me Me Me Me CH2NHCOMe Et CH2CH=CH2 Me CH2CH2NHCOMe Me Me Me Bu Me CH2CH2OH CH2CH2NHCOMe Me Me Me Me CH2CH=CH2 Me CH2CH2NHCOMe CH2CH2NHCOMe CH2CH2NH2 Me Bu Me CH2CH2OH CH2CH2NHCOMe CH2CH2OH CH2CH2NHCOMe Me Me R R1 R2 R3 O R R 1 + H2N(CH2)3NH2 ButOCl, K 2CO3 N N R1 R 7 a R = R1 = H b R = H, R1 = Me c R = R1 = Me d R = CH2NHCOMe, R1 = Me Scheme 3 ‡ General procedure for the synthesis of 1,2-di-, 1,2,3-tri- and 1,2,3,3- tetraalkyldiaziridines with different 1,2-substituents.A solution of 0.1 mol of NaOCl [prepared from 0.21 mol of NaOH and 7.1 g (0.1 mol) of Cl2 in 30 ml of H2O at –5–0 °C] was added dropwise to 0.1 mol 30% aqueous MeNH2 solution at the specified temperature, and MeNHCl was extracted with two 50 ml portions of CHCl3 or CH2Cl2.Then, 0.1 mol of a corresponding amine and 41.5 g (0.3 mol) of K2CO3 were added, the reaction mixture was cooled to –10 °C, and 0.1 mol of a carbonyl compound was added dropwise with stirring for 10–12 h at 20–22 °C (or 24–26 °C for amine or carbonyl compounds with electron-withdrawing substituents). The inorganic precipitate was filtered off and washed with CHCl3 or CH2Cl2, the solvent was distilled off in a vacuum, and the final product was isolated by chromatography on SiO2 L40/100 (eluent: CHCl3, washed two times with equal volumes of 25% NH3) followed by distillation.General procedure for the synthesis of 1,2-di-, 1,2,3-tri- and 1,2,3,3- tetraalkyldiaziridines with identical 1,2-substituents. A solution of 0.1 mol of ButOCl in 20 ml of CHCl3 (CCl4 or CH2Cl2) was added dropwise to a mixture of 0.2 mol of an amine and 41.5 g of K2CO3 in 100 ml of CHCl3 at –5–0 °C with efficient stirring, and after 15 min 0.1 mol of a carbonyl compound was added.The temperature was increased to a required value, and the reaction was carried out as described above. General procedure for the synthesis of 1,5-diazabicyclo[3.1.0]hexanes. The carbonyl compound (0.1 mol) was added to a mixture of 0.1 mol of 1,3-diaminopropane and 41.5 g (0.3 mol) of K2CO3 in 100 ml of CHCl3 (CH2Cl2) at –5–0 °C, and a solution of 0.1 mol of ButOCl in 20 ml of CHCl3 (CH2Cl2 or CCl4) was added dropwise. Next, the reaction was performed as described above.Mendeleev Communications Electronic Version, Issue 5, 2000 (pp. 167–206) 13 A. S. Wheeler and S. Jordan, J. Am. Chem. Soc., 1909, 31, 937. 14 A. Lowy and E. H. Balz, J. Am. Chem. Soc., 1921, 43, 341. 15 R.G. Kostyanovsky, K. S. Zakharov, M. Zaripova and V. F. Rudchenko, Izv. Akad. Nauk SSSR, Ser. Khim., 1975, 875 (in Russian). 16 S. V. Varlamov, G. K. Kadorkina and R. G. Kostyanovsky, Khim. Geterotsikl. Soedin., 1988, 390 [Chem. Heterocycl. Compd. (Engl. Transl.), 1988, 24, 320]. 17 M. Dominikiewcz, Arch. Chem. Pharm., 1935, 2, 160 (Chem. Abstr., 1936, 30, 1030). 18 G. V. Shustov, S.N. Denisenko, I. I. Chervin, N. L. Asfandiarov and R. G. Kostyanovsky, Tetrahedron, 1985, 41, 5719. 19 S. N. Denisenko, G. V. Shustov, I. I. Chervin and R. G. Kostyanovsky, Khim. Geterotsikl. Soedin., 1985, 1348 [Chem. Heterocycl. Compd. (Engl. Transl.), 1985, 21, 21]. 20 G. V. Shustov, S. N. Denisenko, N. L. Asfandiarov, L. P. Khusnutdinova and R. G. Kostyanovsky, Izv. Akad.Nauk SSSR, Ser. Khim., 1980, 1824 (Bull. Acad. Sci. USSR, Div. Chem. Sci., 1980, 36, 1655). 21 V. V. Kuznetsov, N. N. Makhova and M. O. Dekaprilevich, Izv. Akad. Nauk, Ser. Khim., 1999, 623 (Russ. Chem. Bull., 1999, 48, 617). 22 A. N. Mikhailyuk, V. Yu. Petukhova and N. N. Makhova, Mendeleev Commun., 1997, 60. § 1,2-Diallyldiaziridine 3a: yield 32%, bp 99 °C (170 Torr), nD 20 1.4500. 1H NMR (CDCl3) d: 2.3 (s, 2H, ring CH2), 2.90 (dq, 2H, NCH2, 2J –6.0 Hz, 3J 2.0 Hz), 5.0 (m, 2H, CH2=, 3J 9.0 Hz), 5.75 (m, 1H, CH=, 3J 2.0 Hz, 3J 9.0 Hz). IR (n/cm–1): 1650, 3040, 3080. 1-(2-Acetamidoethyl)-2-methyldiaziridine 3d: yield 48%, bp 106–107 °C (1.5 Torr), nD 20 1.4750. 1H NMR (CDCl3) d: 1.95 (s, 3H, MeCO), 2.38 (s, 3H, MeN), 2.1, 2.58 (m, 2H, NringCH2, 2J –11.0 Hz, 3J 5.5 Hz), 2.48 (q, 2H, ring CH2, 2J –6.0 Hz), 3.48 (m, 2H, CH2NCO, 3J 5.5 Hz), 6.3 (br.s, 1H, NH). IR (n/cm–1): 1660, 3050, 3300. 1-(2-Aminoethyl)-2-methyldiaziridine 3e: yield 78%, bp 98 °C (13 Torr), nD 20 1.4812. 1H NMR (CDCl3) d: 2.3, 2.6 (m, 2H, CH2Nring, 2J –11.5 Hz, 3J 5.6 Hz), 2.63 (q, 2H, ring CH2, 2J –6.2 Hz), 2.77 (m, 2H, CH2N, 3J 5.5 Hz), 4.7 (s, 2H, NH2). 13C NMR (CDCl3) d: 41.9 (t, CH2Nring, 1J 134.5 Hz), 48.4 (q, Me, 1J 141 Hz), 59.4 (t, ring CH2, 1J 177 Hz), 64.0 (t, CH2NH2, 1J 129 Hz).IR (n/cm–1): 875, 905, 1045, 1055, 1080, 3190, 3290, 3365. 1,2,3,3-Tetramethyldiaziridine 3h: yield 51%, bp 76 °C (15 Torr), nD 20 1.4370. 1H NMR (CDCl3) d: 1.18 (s, 6H, CMe), 2.34 (s, 6H, NMe). 13C NMR (CDCl3) d: 19.0 (CMe), 39.8 (NMe), 60.5 (diaziridine ring). IR (n/cm–1): 760, 1070, 1150, 1250, 1380, 1470, 1640, 2960. 1,2-Di-(2-hydroxyethyl)-3,3-dimethyldiaziridine 3i: yield 33.7%, undistilled oil, nD 20 1.4810. 1H NMR (CDCl3) d: 1.34 (s, 6H, CMe), 2.50, 2.83 (dt, 4H, NCH2, 2J –13.4 Hz, 3J 4.1 Hz), 3.85 (dt, 4H, OCH2, 3J 4.1 Hz), 4.75 (br. s, 1H, OH). 13C NMR (CDCl3) d: 20.0 (q, Me, 1J 126 Hz), 55.3 (t, NCH2, 1J 135 Hz), 59.2 (s, diaziridine ring), 61.8 (t, OCH2, 1J 142 Hz).IR (n/cm–1): 670, 760, 890, 1070, 1130, 1450, 1480, 1660, 2970, 3310. 1,2-Bis(2-acetamidoethyl)-3,3-dimethyldiaziridine 3j: yield 32.5%, undistilled oil, nD 20 1.4878. 1H NMR (CDCl3) d: 1.26 (s, 6H, CringMe), 1.98 (s, 6H, MeCO), 2.37, 2.72 (dt, 4H, NCH2, 2J –12.0 Hz, 3J 6.0 Hz), 3.29, 3.50 (dt, 4H, CH2NH, 2J –12.0 Hz, 3J 6.0 Hz), 6.58 (br. s, NH). 13C NMR (CDCl3) d: 19.8 (q, CringMe, 1J 127 Hz), 23.1 (q, MeCO, 1J 123 Hz), 39.3 (t, NCH2, 1J 139 Hz), 52.5 (t, CH2NH, 1J 136.0 Hz), 61.2 (s, diaziridine ring), 170.6 (s, CO). IR (n/cm–1): 884, 912, 1000, 1128, 1288, 1376, 1440, 1544, 1664, 2944, 3312. 2-(2-Hydroxyethyl)-1,3,3-trimethyldiaziridine 3k: yield 35.8%, bp 97 °C (1 Torr), nD 20 4.4623. 1H NMR (CDCl3) d: 1.11 (br. s, 6H, CMe), 2.36 (s, 3H, NMe), 2.38, 2.71 (dt, 2H, NCH2, 2J –12.4 Hz, 3J 5.8 Hz), 3.5 (br.s, 1H, OH), 3.67 (t, 2H, OCH2, 3J 5.8 Hz). 13C NMR (CDCl3) d: 18.9, 19.5 (CMe2), 40.0 (NMe), 54.6 (NMe), 60.7 (diaziridine ring), 61.0 (OCH2). 2-(2-Acetamidoethyl)-1,3,3-trimethyldiaziridine 3l: yield 37.6%, bp 102.5 °C (1 Torr), nD 20 1.4650, 1H NMR (CDCl3) d: 1.13 (s, 3H, CMe), 1.15 (s, 3H, CMe), 1.82 (s, 3H, COMe), 2.26 (s, 3H, NMe), 2.22, 2.58 (dt, 2H, NCH2, 2J –12.5 Hz, 3J 5.8 Hz), 3.23, 3.28 (dt, 2H, NHCH2, 2J –12.0 Hz, 3J 5.8 Hz), 6.50 (br.s, 1H, NH). 13C NMR (CDCl3) d: 18.9, 19.2 (CMe2), 22.7 (MeCO), 39.0 (NMe), 40.0 (NCH2), 51.7 (CH2NH), 60.5 (diaziridine ring), 169.7 (CO). 3-Acetamidomethyl-1,2,3-trimethyldiaziridine 3m: yield 34.6%, bp 105 °C (1 Torr), nD 20 1.4742. 1H NMR (CDCl3) d: 1.28 (s, 3H, CringMe), 1.98 (s, MeCO), 2.43, 2.46 (2s, 6H, NMe), 3.43 (d, 2H, CH2N, 3J 5.3 Hz), 6.1 (br. s, 1H, NH). 13C NMR (CDCl3) d: 16.0 (CMe), 23.0 (MeCO), 29.7, 41.4 (NMe), 62.1 (diaziridine ring), 170.1 (CO). IR (n/cm–1): 610, 690, 1000, 1140, 1270, 1380, 1560, 1660, 1888, 3080, 3290. 3-Ethyl-1,2,3-trimethyldiaziridine 3n: yield 34%, bp 89 °C (15 Torr), nD 20 1.4825. 1H NMR (CDCl3) d: 0.85 (t, 3H, CH2Me, 3J 7.1 Hz), 1.07 (s, 3H, CMe), 1.38 (dq, 2H, CCH2, 3J 7.1 Hz), 2.25 (s, 3H, NMe), 2.29 (s, 3H, NMe). 13C NMR (CDCl3) d: 9.5 (MeCH2), 15.6 (CringMe), 25.8 (CringCH2), 39.3, 39.9 (NMe), 64.0 (diaziridine ring). IR (n/cm–1): 970, 1410, 1460, 1640, 2990. 6-Acetamidomethyl-6-methyl-1,5-diazabicyclo[3.1.0]hexane 7d: yield 52%, undistilled oil, nD 20 1.4365. 1H NMR (CDCl3) d: 0.90 (s, 3H, CringMe), 1.71 (s, 3H, MeCO), 1.68, 1.96 (m, 2H, 2J –13.0 Hz, 3J2a–3a 11.5 Hz, 3J2a–3e 7.0 Hz, 3J2e–3a 10.1 Hz, 3J2e–3e 4.7 Hz), 2.60, 2.93 (m, 4H, NCH2, 2J –11.5 Hz, 3J2a–3a 11.5 Hz, 3J2a–3e 7.0 Hz, 3J2e–3a 10.1 Hz, 3J2e–3e 4.7 Hz), 3.0 (d, 2H, CringCH2, 3J 5.1 Hz), 6.60 (br. s, 1H, NH). 13C NMR (CDCl3) d: 9.7 (CringMe), 22.5 (MeCO), 32.0 (CCC), 46.5 (CH2NH), 47.2 (CH2N), 61.6 (diaziridine ring), 170.0 (CO). IR (n/cm–1): 732, 1040, 1256, 1376, 1464, 1652, 2888, 2944, 3280. Received: 26th June 2000; Com. 00/1676

ISSN:0959-9436     

出版商:RSC    

年代:2000

数据来源: RSC