Subscribe to RSS
DOI: 10.1055/s-2004-825607
Synthesis of N,N-Dimethylpropanediamide and its Utility for the Preparation of 2-(Acetamidomethyl)-4-aryloxazoles
Publication History
Publication Date:
18 May 2004 (online)
![](https://www.thieme-connect.de/media/synlett/200408/lookinside/thumbnails/10.1055-s-2004-825607-1.jpg)
Abstract
A practical, readily scaleable synthesis of N,N-dimethylpropanediamide (1) is reported. The utility of this bis-amide is demonstrated in the preparation of several 2,4-disubstituted oxazoles from α-bromoketones.
Key words
oxazole - bromo-ketone - annulation - N,N-dimethylpropanediamide - heterocycle
- 1
Hartner FW. In Comprehensive Heterocyclic Chemistry II Vol. 3:Katritzky AR.Rees CW.Scriven EFV. Pergamon; Oxford: 1996. p.262-318 ; and references therein -
2a
Friedman BS.Sparks M.Adams R. J. Am. Chem. Soc. 1937, 59: 2262 -
2b
Panek JS.Beresis RT. J. Org. Chem. 1996, 61: 6496 -
2c
Takechi H.Oda Y.Hishizono N.Oda K.Machida M. Chem. Pharm. Bull. 2000, 48: 1702 -
3a
Gellman SH.Dado GP.Liang G.-B.Adams BR. J. Am. Chem. Soc. 1991, 113: 1164 -
3b
Interestingly, both Beilstein and Sci-Finder searches for bis-amide 1 gave the preceding reference for its synthesis. We suspect that this was a typographical error upon entry in these databases, as there is no description of compound 1 in the Gellman paper. The Beilstein reference gives a reaction time of 63 h and 81% yield, values which are identical to the first experimental procedure in the paper, in which the mono-N,N-dimethylamide of malonic acid (3) is prepared en route to N,N,N′-trimethylpropanediamide.
- 4 This effect has recently been noted in the esterification of carboxylic acids activated at the α-carbon with phosphonates, esters, sulfones, and nitriles. A mechanism proceeding through an acyl ketene was supported by trapping of the ketene with DCC in a [4+2] cycloaddition:
Shelkov R.Nahmanh M.Melman A. J. Org. Chem. 2002, 67: 8975
References
Intermediacy of a ketene is also supported by the following experiment: exposure of ethyl benzoate to the same reaction conditions (2 N Me2NH in MeOH) for several days showed no detectable formation of N,N-dimethylbenzamide by 1H NMR or GC/MS.
6Actually, the opposite enantiomer of the other diastereomer would be formed. For example, in the condensation of the R-acid chloride with racemic amine, the products are amide 10 and (ent)-11. This has no impact on the achiral HPLC and NMR analyses, however.