摘要:
Reaction of Imines with Trichloroacetic Esters or Anhydride Promoted by Iron Carbonyl or Microwave Irradiation. Preparation of 3,3-Dichloro-b-Lactams$ Mohammad S. Khajavi,* Fatemeh Sefidkon and S. S. Sadat Hosseini Department of Chemistry, Faculty of Science, Shahid Beheshti University, Tehran, Iran The synthesis of 3,3-dichloroazetidin-2-ones by the reaction of imines and methyl or trimethylsilyl trichloroacetate promoted by diiron nonacarbonyl or by microwave irradiation of imines and trichloroacetic anhydride is described.Monocyclic b-lactams are an important class of hetero- cyclic compounds because of their use in the synthesis of biologically active classical or non-classical b-lactam anti- biotics.1 The cycloaddition of substituted acetic acid deriva- tives with imines has become one of the major routes for the synthesis of b-lactams.2 Here we wish to report a novel method for the synthesis of 3,3-dichloro-b-lactams by the condensation of an imine with the methyl or trimethyl- silyl ester of trichloroacetic acid (1a,b) promoted by diiron nonacarbonyl through an enolate intermediate (2).The preparation of 3,3-dihalo-b-lactams by the reaction of a Schi€ base with trimethylsilyl trihaloacetate and tri- phenylphosphine has been described previously.3 Noyori et al. have described the reaction of dibromo ketones with iron carbonyls to produce an oxyallyl-iron(II) complex by the mechanism outlined in Scheme 1.4 Accordingly, we decided to extend this successful iron carbonyl reduction of a,a'-dihalo ketones to iron(II) dichloro enolate (2) formation.Our initial experiments showed that imines reacted with methyl trichloroacetate in the presence of diiron nonacarbonyl to a€ord poor yields of b-lactams (3). Subsequently, it was found that the yields of the desired b-lactams increase when the imines were treated with boron tri�Puoride etherate. In the presence of BF3 the imines, to some extent, cannot form a complex with diiron nona- carbonyl.5 Kamiya has utilized the BF3 complex of monomeric formaldehyde imines for the preparation of 4-unsubstituted b-lactams.6 Thus, it was found that when a mixture of methyl or trimethylsilyl trichloroacetate (1a,b) and diiron nonacarbonyl in dry benzene was treated with an equimolar amount of the N-benzylideneaniline�} boron tri�Puoride complex at 50 8C, 3,3-dichloro-1,4-diphenyl azetidin-2-one (3c) was isolated in 65% yield.A number of 3,3-dichloro-b-lactams with various substituents were prepared by this procedure (Table 1).To the best of our knowledge, there have been no studies on the synthesis of diahalo-b-lactams using the ester of trichloroacetic acid promoted by iron carbonyl. Noteworthy is that changing the trichloroacetate from methyl (1a) to trimethylsilyl (1b) did not greatly improve the yields of the desired b-lactams. A possible mechanism for this dichloro-b-lactam formation is suggested in Scheme 2.The formation of iron(II) dichloro enolate (2) from the methyl or trimethylsilyl ester of trichloroacetic acid has an analogy in the mechanism of Noyori4 for the formation of the iron enolate (4) in Scheme 1. The reaction of the in situ prepared 2 with imines would be similar to the condensation of lithium ester enolates with imines.7 Furthermore, Sekiya8 has reported that the reaction of trichloroacetic anhydride with imines in re�Puxing xylene over a period of 1�}8 h, led to 3,3-dichloro-b-lactams.As part of our programme to study the highly accelerated synthesis of heterocyclic compounds under microwave irradiation,9 we examined this reaction under such irra- diation and it was found that the reaction of trichloroacetic anhydride with the imines results in the rapid formation of b-lactams (3a�}g) in high yield when the reactions were conducted in a tall beaker covered with a stemless funnel in a microwave oven. The results are summarized in Table 1.In conclusion, we have developed a new procedure for the synthesis of 3,3-dichloro-b-lactams by the condensation of iron(II) dichloro-enolate and imines; this is a rapid method under microwave irradiation. Work is continuing in this area to extend these reactions to other tri- and di-haloacetic esters. Experimental IR spectra were recorded as KBr pellets on a Shimadzu IR-470 spectrophotometer. 1H NMR spectra were obtained on a Bruker AC 80 or JEOL-EX-90 instrument.Microwave irradiations were carried out in a National oven, Model 5250, at 2450 MHz. Melting points are uncorrected and were determined in open capillary tubes using Mel-Temp apparatus. Benzene and m-xylene were dried over sodium and freshly distilled before use. Diiron nonacar- bonyl (Aldrich), trichloroacetic anhydride (Fluka) and methyl trichloroacetate (Aldrich) were used as received. Trimethylsilyl tri- chloroacetate was readily prepared by the reaction of hexamethyl- disilazane and trichloroacetic acid.11 For safety reasons all experiments with microwave ovens should be performed in an ecient hood to avoid contact with vapours.If J. Chem. Research (S), 1998, 724�}725$ Scheme 1 Scheme 2 $This is a Short Paper as deRned in the Instructions for Authors, Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is there- fore no corresponding material in J. Chem. Research (M). *To receive any correspondence. Present address: Organization for the Prohibition of Chemical Weapons, Johan de Wittlaan 32, 2517 JR, The Hague, The Netherlands. 724 J. CHEM. RESEARCH (S), 1998Table 1 b-Lactams from trichloroacetic esters or anhydride and iminesMethod A Method B, irradiation conditionsb Mp Lit. mpEntry Product R1 R2 Yield (%)a (1)P/W t/min (2)P/W t/min Yield (%)a (T/8C) (T/8C)1 3a MeOC6H4 PhCH2 60 70 1 210 1.5 72 104¡Ó106 ¡Ó2 3b Ph PhCH2 64 70 1 210 1.5 68 46¡Ó48 45¡Ó4683 3c Ph Ph 65 70 2 210 1.5 80 162¡Ó164 164104 3d Ph MeOC6H4 75 70 1.5 210 1.5 84 110¡Ó111 110.5¡Ó11285 3e Ph ClC6H4 68 70 2 210 2 74 129¡Ó131 131¡Ó13286 3f MeOC6H4 Ph 72 70 1.5 210 2 79 155¡Ó156 154¡Ó15587 3g ClC6H4 Ph 78 70 2 210 2 77 130¡Ó132 130¡Ó1318aYield of pure, isolated product based on imines.b To control the reaction the irradiation was carried out in two stages, with a coolingperiod between each irradiation.a tall beaker covered with a watch glass or a small stemless funnelis used and the microwave irradiation period is interrupted witha 5 min cooling period there is little vaporization and very highconversions can be observed.Preparation of 3,3-Dichloro--lactams (Method A).The generalprocedure is illustrated with 1-benzyl-3,3-dichloro-4-p-anisylazetidin-2-one (3a).In a ame-dried three-necked ask, equipped with adropping funnel, a condenser and a three-way stopcock attached toa dry nitrogen inlet tube, was placed 3.64 g, 10 mmol of diiron non-acarbonyl and the system was evacuated then ushed with nitrogen.To this were added 20 ml of dry benzene and then 1.8 g, 10 mmolof methyl trichloroacetate or 2.36 g, 10 mmol of trimethylsilyl tri-chloroacetate and the resultant mixture stirred at room temperaturewhile a benzene 30 ml solution of 2.25 g, 10 mmol of N-p-methoxy-benzylidenebenzylamine and an equimolar amount of borontriuoride etherate was added dropwise over a 10 min period.Theresulting reaction mixture was stirred at 50 8C for 48 h. The precipi-tates that formed were removed by ltration through a pad ofCelite.Evaporation of benzene gave the crude product which waschromatographed on silica gel (100¡Ó200 mesh), using dichloro-methane¡Óhexane (50:50) as eluent gave the title compound in60% yield, mp 104¡Ó106 8C (from hexane and diethyl ether) (Found:C, 61.13; H, 4.53; N, 4.13. C17H15Cl2NO2 requires C, 60.73; H, 4.49;N, 4.16%); max/cm£¾1 (KBr) 1786; H (CDCl3) 3.75 (s, 3 H, OCH3),3.87 (d, 1 H, J 13.7 Hz), 4.82 (s, 1 H, C4-H), 4.91 (d, 1 H, J13.7 Hz), 6.87¡Ó7.46 (m, 9 H, Ar-H).Preparation of 3,3-Dichloro--lactams (Method B).The generalprocedure is illustrated with 3,3-dichloro-1,4-diphenylazetidin-2-one(3c). A mixture of N-benzylideneaniline (1.81 g, 10 mmol) andt anhydride (3.4 g, 11 mmol) in 8 ml of m-xylene con-tained in a tall beaker was placed in the microwave oven and thebeaker was covered with a stemless funnel and irradiated for 2 minat 70 W, and after 10 min (during this time the mixture cools slowlyto room temperature) it was irradiated again at 210 W for 1.5 min.The solvent was evaporated under reduced pressure.Trituration ofthe crude residue with diethyl ether led to the title compound whichwas recrystallized from ethanol and hexane to give an 80% yieldof 3c, mp 162¡Ó164 8C (lit.,10 164 8C); max/cm1 (KBr) 1767; H(CDCl3) 5.59 (s, 1 H, C4-H), 7.11¡Ó7.48 (m, 10 H, Ar-H).3b: max/cm£¾1 (KBr) 1782; dH (CDCl3) 3.82 (d, 1 H, J 13.6 Hz),4.71 (s, 1 H, C4-H), 4.86 (d, 1 H, J 13.6 Hz), 6.85¡Ó7.61 (m, 10 H,Ar-H).3d: max/cm£¾1 (KBr) 1776; dH (CDCl3) 3.73 (s, 3 H, OCH3), 5.45(s, 1 H, C4-H), 6.82¡Ó7.93 (m, 9 H, Ar-H).3e: max/cm£¾1 (KBr) 1785; dH (CDCl3) 5.48 (s, 1 H, C4-H), 7.21¡Ó7.67 (m, 9 H, Ar-H).3f: max/cm£¾1 (KBr) 1770; dH (CDCl3) 3.78 (s, 3 H, OCH3), 5.41(s, 1 H, C4-H), 6.63¡Ó7.45 (m, 9 H, Ar-H).3g: max/cm£¾1 (KBr) 1774; dH (CDCl3) 5.48 (s, 1 H, C4-H), 7.05¡Ó7.63 (m, 9 H, Ar-H).We are grateful to the late Professor T.Kametani andProfessor T.Honda for support of the early part of thework done at the Institute of Medicinal Chemistry at HoshiUniversity in Tokyo.Received, 8th June 1998; Accepted, 29th July 1998Paper E/8/04314KReferences1 (a) T. Kametani, Heterocycles, 1982, 17, 463; (b) R. B. Morinand M. Gorman, Chemistry and Biology of -Lactam Antibiotics,Academic Press, New York, 1982, vols. 1¡Ó3; (c) T. Nagaharaand T. Kametani, Heterocycles, 1987, 25, 729.2 (a) A. K. Bose, M. S. Manhas, J.M. Van Der Veen, S. G.Amin, I. F. Firnandez, K. Gala, R. Gruska, J. C. Kapur, M. S.Khajavi, J. Kreder, L. Mukkavilli, B. Ram, M. Sugiura andJ. E. Vincent, Tetrahedron, 1981, 37, 2321, and references citedtherein; (b) M. S. Manhas, A. K. Bose and M. S. Khajavi,Synthesis, 1981, 209.3 M. S. Manhas, M. S. Khajavi, S. S. Bari and A. K. Bose,Tetrahedron Lett., 1983, 24, 2323.4 (a) R. Noyori, Y. Hayakawa, H. Takaya, S. Murai, R. Kobayashiand N. Sonoda, J. Am. Chem. Soc., 1978, 100, 1759; (b) R. Noyoriand Y. Hayakawa, Tetrahedron, 1985, 41, 5879, and referencescited therein.5 For a similar improvement in yields see H. Takaya, S. Makino,Y. Hayakawa and R. Noyori, J. Am. Chem. Soc., 1978, 100,1765.6 T. Kamiya, T. Oku, O. Nakaguchi, H. Takeno and M. Hashimoto,Tetrahedron Lett., 1978, 5119.7 (a) A. K. Bose, M. S. Khajavi and M. S. Manhas, Synthesis,1982, 407; (b) F. H. van der Steen, H. Kleijn, A. L. Spek andG. van Koten, J. Org. Chem., 1991, 56, 5868; (c) L. E. Overmanand T. Osawa, J. Am. Chem. Soc., 1985, 107, 1698; for reviewsof the ester enolate imine condensation, see (d) M. J. Brown,Heterocycles, 1989, 29, 2225; (e) D. J. Hart and D.-C. Ha,Chem. Rev. 1989, 89, 1447.8 M. Sekiya and T. Morimoto, Chem. Pharm. Bull., 1975, 23,2353.9 (a) M. S. Khajava, N. Montazari and S. S. Sadat Hosseini,J. Chem. Res. (S), 1997, 286; (b) M. S. Khajavi, M. Hajihadiand R. Naderi, J. Chem. Res. (S), 1996, 92.10 E. Ziegler, Th. Wimmer and H. Mittelbach, Monatsh. Chem.,1968, 99, 2128.11 G. A. Gornowicz and J. W. Ryan, J. Org. Chem., 1966, 31,3439.J. CHEM. RESEARCH (S), 1998 725
ISSN:0308-2342
DOI:10.1039/a804314k
出版商:RSC
年代:1998
数据来源: RSC