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Mendeleev Communications Electronic Version, Issue 2, 1998 (pp. 43–82) Reaction of glycidol with dichloroethers: cyclic and acyclic ortho ester formation Alexander A. Bredikhin* and Sergey N. Lazarev 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: baa@glass.ksu.ras.ru The interaction of stoichiometric quantities of glycidol with alkyl dichloromethyl ethers in the presence of 2 equiv.of NEt3 in diethyl ether leads to formation of diglycidyloxy alkoxy methanes whereas the same reaction involving equimolar quantities of the reagents in benzene in the presence of 1 equiv. of NEt3 leads to formation of 4-chloromethyl-2-alkoxy-1,3-dioxolanes. 2,3-Epoxy alcohols and parental glycidol 1 are examples of bifunctional organic compounds widely used in organic synthesis.1 The value of 2,3-epoxy alcohols as building blocks in organic synthesis has been greatly increased with the development by Sharpless and his group of a simple and straightforward procedure to produce these compounds in enantiopure form with the desired configuration.2 However, the most common way to use them in synthesis involves the hydroxy and epoxy functions separately in reactions with different reagents.We recently described the formation of the 4-chloromethyl- 1,3,2-dioxaphospholanes in the reactions of glycidol with PCl3 and other phosphorus compounds possessing a –P(X)Cl2 fragment (X = lone pair, O).3 In these processes, which have usually been achieved as one-pot procedures, a single molecule with at least two active P–Cl bonds takes part in a sequence of substitution and addition reactions involving both the hydroxy and epoxy functions of the glycidol as a substrate. We believe that the scheme for converting the 2,3-epoxy alcohols to the 4-halomethyl- 1,3-dioxacyclane fragments through the interaction with activated geminal dihalogenides has general value.Here we report the predominant formation (according to the protocol chosen) of either linear or cyclic ortho esters in the reactions of alkyl dichloro methyl ethers 2a–c with racemic glycidol. The latter reaction course confirms our above-mentioned expectations. It is deemed that a,a-dichloroethers do not exchange both chlorine atoms by alkoxy groups on reaction with alcohols.The usual result of these reactions is the formation of alkyl chlorides and alkyl formates:4 When glycidol reacts with a,a-dichloromethyl methyl ether 2a in the absence of any base methyl formate and (ClCH2)2CHOH (54%) are the only products isolated. Their formation is consistent with the above scheme if one takes into account the possibility of subsequent HCl addition to epichlorohydrin (RCl) formed in the early step.The known method of obtaining linear ortho esters from a,a-dichloroethers involves reaction of the latter compounds with alcoholates of alkali metals.5 We found that in the presence of 2 equiv. of NEt3 glycidol reacts smoothly with 2a–c forming the ortho esters 3a–c in moderate to good isolated yields.† Obviously the compounds 3 are generated from (±)-1 in diastereoisomeric forms, but they do not manifest themselves in the routine 1H NMR spectra (the numbering of the atoms corresponds to Scheme 1).‡ On the contrary, some signals in the 13C-{H} NMR spectra consist of several (up to three) different lines in an approximate intensity ratio in the last case of 1:1:2 (in any order).This picture agrees well with the simultaneous existence in the mixture of a chiral R,R(S,S)-diastereoisomer (signal of double intensity) and two different achiral meso-forms with pseudo chiral r- and s-atoms C-4. The alternative reaction path completely dominated when reagents 1 and 2 (1:1) and 1 equiv. of NEt3 were mixed in benzene at ca. 0 °C and then boiled for 2 h.The cyclic ortho esters 4a–c were isolated as a mixture of almost equal quantities of cis and trans diastereoisomers (the numbering of the atoms corresponds to Scheme 1).‡ The assignment of the isomers is based on the known fact6 that the low field signal of the proton bound to C-2 in the 1H NMR spectra and the high field signal of the atom C-2 itself in the 13C NMR spectra of the 2,4-disubstituted 1,3-dioxolanes belong to the trans isomers.The usual method of producing the cyclic ortho esters involves transesterification of linear ones by the corresponding diols or by reaction of 1,3-dioxacycloalkanium salts with the alcoholates of alkali metals.7 In particular, all known 4-chloromethyl- 2-alkoxy-1,3-dioxolanes (and the compound 4b among them) were obtained from 3-chloropropen-1,2-diol by the former procedure.8 The method introduced here appears to be a quite new approach to the synthesis of cyclic ortho esters.We are grateful to Dr. T. A. Zyablikova and Dr. Z. A.Bredikhina for collaboration in the work. References 1 R. M. Hanson, Chem. Rev., 1991, 91, 437. 2 R. A. Johnson and K. B. Sharpless, in Catalytic Asymmetric Synthesis, ed.I. Ojima, VCH, New York, 1993, p. 103. 3 (a) A. A. Bredikhin, O. R. Sharapov, A. N. Ustyugov and V. A. Al’fonsov, Zh. Obshch. Khim., 1996, 66, 2057 (Russ. J. Gen. Chem., 1996, 2001); (b) A. A. Bredikhin, S. N. Lazarev and Z. A. Bredikhina, Zh. Obshch. Khim., 1997, 67, 1806 (in Russian); (c) A. A. Bredikhin, S. N. Lazarev, Z. A. Bredikhina and V. A. Al’fonsov, Phosphorus Sulfur Relat.Elem., in press. † In a typical procedure an ethereal solution of glycidol (2 equiv.) and NEt3 (2 equiv.) was added to a stirred ethereal solution of dichloro ether (1 equiv.) at less than –30 °C. The reaction mixture was allowed to warm to room temperature and was then boiled for ca. 5 min. After cooling and removal of solid deposit and solvent the crude mixture was fractionated in vacuo.HOCH2 CH CH2 O RP(X)Cl2 + RP(X)OCH2 CH CH2 O Cl P O O X R CH2Cl 1 AlkOCH(OCH2CH CH2)2 O AlkO CH O O CH2Cl 1 + AlkOCHCl2 2:1; 2 equiv. NEt3; ether 1:1; 1 equiv. NEt3; benzene 40–70% 50–70% 2a–c 3a–c 4a–c a Alk = Me b Alk = Et c Alk = Prn Scheme 1 1 2 3 4 5 4 3 2 1 AlkOCHCl2 + ROH HCOOAlk + RCl + HCl MeOCHCl2 + 1 HCOOMe + ClH2CCH(OH)CH2ClMendeleev Communications Electronic Version, Issue 2, 1998 (pp. 43-82) 4 A. Rieche and H. Gross, Angew. Chem., 1957, 69, 726. 5 H. Gross and A. Rieche, Chem. Ber., 1961, 94, 538. 6 (a) W. E. Willy, G. Binsch and E. L. Eliel, J. Am. Chem. Soc., 1970, 92, 5394; (b) E. L. Eliel, V. S. Rao and K. M. Pietrusiewicz, Org. Magn. Reson., 1979, 12, 461. 7 D. L. Rakhmankulov, S. S. Zlotskii, R. A. Karakhanov and E.A. Kantor, Khimiya ortoefirov (The Chemistry of Ortho Esters), Itogi Nauki Tekh., Ser. Tekhnologiya organicheskikh veshchestv, VINITI, Moscow, 1986, vol. 11, p. 1 (in Russian). 8 D. Kurbanov, I. Kurbanov, Yu. K. Khekimov, S. S. Zlotskii and D. L. Rakhmankulov, Zh. Org. Khim., 1991, 27, 1083 (Russ. J. Org. Chem., 1991, 27, 937). ‡ 3a: yield 46%, bp 99–104 °C (1 mmHg). 1H NMR (250.132 MHz, CDCl3) d: 4.73 (s, 1H, 4-H), 3.38–3.32 and 3.00–2.92 (m, 2H, 3-H), 2.85 (s, 3H, 4b-H), 2.69–2.64 (m, 1H, 2-H), 2.32–2.27 and 2.13–2.09 (m, 2H, 1-H); 13C NMR (100.624 MHz, CDCl3) d: 112.38 (d, C-4, 1JCH = 189.6, 189.3 and 192.5 Hz), 64.11 and 64.01 (t, C-3, 1JCH = = 143.5 and 143.7 Hz), 50.93, 50.89 and 50.88 (q, C-4b, 1JCH = 143.4, 143.3 and 143.3 Hz), 49.48 (d, C-2, 1JCH = 176.7 Hz), 43.41 (t, C-1, 1JCH = 175.7 Hz). 3b: yield 49%, bp 105–108 °C (1 mmHg). 1H NMR (250.132 MHz, CCl4 + C6D6) d: 5.30 (s, 1H, 4-H), 3.88–3.81 and 3.53–3.44 (m, 2H, 3-H), 3.67 (q, 2H, 4b-H, 3JHH = 7.1 Hz), 3.17–3.13 (m, 1H, 2-H), 2.78– 2.73 and 2.60–2.57 (m, 2H, 1-H), 1.27 (t, 3H, 4g-H, 3JHH = 7.1 Hz); 13C NMR (100.624 MHz, CCl4 + C6D6) d: 112.37 (d, C-4, 1JCH = 188.7 and 191.5 Hz), 64.65, 64.57 and 64.48 (t, C-3, 1JCH = 143.3, 143.3 and 143.3 Hz), 59.95 and 59.92 (t, C-4b, 1JCH = 142.9 and 142.8, 142.9 Hz), 49.99 and 49.97 (d, C-2, 1JCH = 175.9 and 175.9 Hz), 43.71 (t, C-1, 1JCH = 175.4 Hz), 14.71 (q, C-4g, 1JCH = 126.2 Hz). 3c: yield 72%, bp 107–110 °C (1 mmHg). 1H NMR (250.132 MHz, CCl4 + C6D6) d: 5.30 (s, 1H, 4-H), 3.88–3.82 and 3.56–3.46 (m, 2H, 3-H), 3.55 (q, 2H, 4b-H, 3JHH = 7.0 Hz), 3.17–3.12 (m, 1H, 2-H), 2.77–2.75 and 2.61-2.58 (m, 2H, 1-H), 1.75–1.61 (m, 2H, 4g-H), 1.04 (t, 3H, 4d-H, 3JHH = 7.4 Hz); 13C NMR (100.624 MHz, CCl4 + C6D6) d: 112.39 (d, C-4, 1JCH = 188.5 and 185.7 Hz), 66.01 and 65.98 (t, C-4b, 1JCH = 146.6 and 145.1 Hz), 64.52, 64.45 and 64.35 (t, C-3, 1JCH = = 144.3, 144.3 and 144.3 Hz), 49.93 and 49.92 (d, C-2, 1JCH = 175.8 and 175.8 Hz), 43.68 and 43.65 (t, C-1, 1JCH = 174.3 and 174.9 Hz), 22.59 (t, C-4g, 1JCH = 127.6, 126.1 and 124.6 Hz), 10.42 and 10.41 (q, C-4d, 1JCH = 125.6, 125.5 and 125.5 Hz). 4a: yield 54%, cis:trans 1:1, bp 93–97 °C (30 mmHg). 1HNMR (250.132MHz, CDCl3) d: 5.58 (s, 1H, trans-2-H), 5.54 (s, 1H, cis-2-H), 4.33–4.25 and 4.20–4.09 (m, 1H, 4-H), 3.99–3.92 and 3.71–3.65 (m, 2H, 5-H), 3.55–3.46 and 3.42–3.30 (m, 2H, 4a-H), 3.10 (s, 3H, cis-2d-H), 3.09 (s, 3H, trans-2d-H); 13C NMR (100.624 MHz, CDCl3) d: 115.90 (d, cis-C-2, 1JCH = 200.8 Hz), 115.59 (d, trans-C-2, 1JCH = = 199.1 Hz), 74.83 (d, cis-C-4, 1JCH = 155.7 Hz), 74.20 (d, trans-C-4, 1JCH = 154.3 Hz), 66.56 (t, cis-C-5, 1JCH = 150.7 Hz), 65.72 (t, trans-C-5, 1JCH = 151.0 Hz), 50.82 (q, cis-C-2b, 1JCH = 143.0 Hz), 50.57 (q, trans- C-2b, 1JCH = 143.0 Hz), 44.24 (t, cis-C-4a, 1JCH = 152.1 Hz), 43.56 (t, trans-C-4a, 1JCH = 151.5 Hz). 4b: yield 69%, cis:trans 1.4:1, bp 77–81 °C (12 mmHg). 1H NMR (250.132 MHz, CDCl3) d: 5.50 (s, 1H, trans-2-H), 5.46 (s, 1H, cis-2-H), 4.34–3.95 and 4.18–4.11 (m, 1H, 4-H), 3.85–3.76 and 3.58–3.49 (m, 2H, 5-H), 3.41–3.35 and 3.27–3.17 (m, 2H, 4a-H), 3.23 (q, 2H, 2b-H, 3JHH = 7.1 Hz), 0.85 (t, 3H, 2d-H, 3JHH = 7.1 Hz); 13C NMR (100.624 MHz, CDCl3) d: 115.22 (d, cis-C-2, 1JCH = 198.3 Hz), 114.91 (d, trans-C-2, 1JCH = 198.4 Hz), 74.77 (d, cis-C-4, 1JCH = 156.2 Hz), 74.11 (d, trans-C-4, 1JCH = 154.4 Hz), 66.69 (t, cis-C-5, 1JCH = 150.5 Hz), 65.67 (t, trans-C-5, 1JCH = 150.9 Hz), 59.77 (t, cis-C-2b, 1JCH = = 143.4 Hz), 59.53 (t, trans-C-2b, 1JCH = 142.4 Hz), 44.27 (t, cis-C-4a, 1JCH = 152.2 Hz), 43.51 (t, trans-C-4a, 1JCH = 150.2 Hz), 14.31 (q, C-2g, 1JCH = 126.8 Hz). 4c: yield 69%, cis:trans 1.5:1, bp 93–98 °C (18 mmHg). 1H NMR (250.132 MHz, CDCl3) d: 5.66 (s, 1H, trans-2-H), 5.63 (s, 1H, cis-2-H), 4.35–4.27 and 4.20–4.13 (m, 1H, 4-H), 4.01–3.93 and 3.75–3.67 (m, 2H, 5-H), 3.57–3.48 and 3.43–3.34 (m, 2H, 4a-H), 3.29 (t, 2H, 2b-H, 3JHH = 7.0 Hz), 1.48–1.34 (m, 2H, 2g-H), 0.74 (t, 3H, 2d-H, 3JHH = = 7.5 Hz). 13C NMR (100.624 MHz, CCl4 + C6D6) d: 115.88 (d, cis-C-2, 1JCH = 198.0 Hz), 115.53 (d, trans-C-2, 1JCH = 197.8 Hz), 75.11 (d, cis-C-4, 1JCH = 154.3 Hz), 74.50 (d, trans-C-4, 1JCH = 154.5 Hz), 67.12 (t, cis-C-5, 1JCH = 149.8 Hz), 66.12 (t, trans-C-5, 1JCH = 150.7 Hz), 66.07 (t, cis-C-2b, 1JCH = 148.5 Hz), 65.71 (t, trans-C-2b, 1JCH = = 148.2 Hz), 44.71 (t, cis-C-4a, 1JCH = 152.2 Hz), 43.84 (t, trans-C-4a, 1JCH = 151.3 Hz), 22.61 (t, C-2g, 1JCH = 126.7 Hz), 10.38 (q, cis-C-2d, 1JCH = 125.4 Hz), 10.34 (q, trans-C-2d, 1JCH = 125.7 Hz). Received: Moscow, 25th December 1997 Cambridge, 25th March 1997; Com. 8/00168E

ISSN:0959-9436     

出版商:RSC    

年代:1998

数据来源: RSC