Third International Electronic Conference on Synthetic Organic Chemistry (ECSOC-3), www.mdpi.org/ecsoc-3.htm, September 1-30, 1999

[a0027] 

SYNTHESIS OF 3-BENZYLIDENE-1-METHYLPYRROLIDIN-2-ONE THROUGH 3-CHLOROMETHYLENE-1-METHYLPYRROLIDIN-2-ONE

Julio A. Seijas*, M. Pilar Vázquez-Tato*, Luis Barreiro-Castro and Pablo Díaz

Received: 5 August 1999 / Uploaded: 22 August 1999

 Introduction of a carbon chain in the -position of amides is a common step to many organic synthesis. Here we describe an improvement in a simple way to achieve 3-chloromethylene-1-methylpyrrolidin-2-one 2, and its reaction with phenyllithium/CuCN to afford 3-arylidene-1-methylpirrolidin-2-one (3), this would represent an approach to a kind of carbon skeleton present in a wide variety of pharmacologically active compounds¹. The preparation of 2 was previously reported² by addition of dichlorocarbene to N-methyl-2-pyrrolidone (1) under phase transfer catalysis (PTC), but the yield reported , using Bu₄NCl, was too low (30%) to make it a practical way to achieve 2 in a preparative scale.

 As we became interested in compounds like 3, through 2, we did some attempts to get a yield that was useful for a preparative scale. The procedure was described as a phase transfer addition of dichlorocarbene followed of a ß-elimination, as both steps were phase-transfer catalyzed, we thought that we should focus our efforts in the nature of the catalyst. When Bu₄NBr, instead of the chloride, was used we achieved only a slight improvement in the yield (39%), a change towards more lipophylic catalysts showed a noteworthy improvement, with adogen ((CH₃(CH₂)₇)₃NCl) a 60% of addition elimination product was obtained, and with cetyltrimetilammonium bromide (CH₃(CH₂)₇NMe₃Br) the yield was similar (62%)
 

 As an application of this product to the synthesis of 3-arylidenepyrrolidin-2-ones. Compound 2 was treated with PhLi/CuCN in ethyl ether at 0ºC and left overnight at r. t., as expected the phenyl ring gave a conjugated addition to the C=C, followed by chloride elimination regenerating the C=C, thus 3 was obtained in 78% yield.

 We think that with this report it is opened an easy access to 2 which could be used as a versatile synthon whose position  to carbonyl shows a functionality that can be interconverted with another groups, allowing to use this procedure as an intermediate step in the design of synthetic strategies. On the other hand the addtion-elimination of PhLi to 2, opens a new route to the 3-arylidene-1-methylpirrolidin-2-ones, in fact actually we are investigating the application of this strategy to a variety of substitution in the aromatic ring and in the pyrrolinone nucleus.

ACKNOWLEDGMENTS

 We thank Dirección General de Enseñanza Superior (DGES) for its financial support (PB96-0932).

REFERENCES

1.- H. Ikuta, h. Shiroda, S. Kobayashi, Y. Yamagishi, K. Yamada, I. Yamatsu, K. Katayama, J. Med. Chem., 1987, 30, 1995-1998. I. Katsumi, H. Kondo, Y. Fuse, K. Yamashita, T. Hidaka, K. Takeo, T. Yamashita, K. Watanabe, Chem. Pharm, Bull., 1986, 30, 1619-1627

2.-J. L. Castro, M. Marcos, L. Castedo, and R. Riguera, TetrahedronLett. (1986), 41, 649-653.

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