[6780-49-0] · C9H11NO · N-Ethoxymethyleneaniline · (MW 149.19)
Alternate Name: ethyl N-phenylformimidate.
Physical Data: bp 87-88 °C/10 mmHg.
Form Supplied in: liquid, commercially available; best preparation is from Triethyl Orthoformate and aniline.4
Handling, Storage, and Precautions: store refrigerated under dry nitrogen.
Of the various older methods reviewed1 for the synthesis of aldehydes from Grignard reagents, use of this imidate reagent was considered one of the best,2 giving higher yields than Triethyl Orthoformate.1a However, newer procedures have been developed that may yield superior results, e.g. treatment of Grignard reagents with Pentacarbonyliron.5 The reaction proceeds through the formation of the imine which is hydrolyzed to the aldehyde (eq 1).2 Cyclohexane-1,3-dione also adds to the imidate, and upon hydrolysis of the intermediate 2-(phenylamino)methylene gives the 2-formylcyclohexane-1,3-dione.6,7
Recent reinvestigation of the above reaction has demonstrated that the reagent can also be utilized for the synthesis of a variety of ketones, by using 2 equiv of a Grignard reagent (80 °C) or alkyllithium (-30 °C).8 This involves the addition of a second Grignard reagent or, preferably, an alkyllithium to the first-formed imine. Aqueous hydrolysis gives N-disubstituted methylaniline (ca. 100% yield) which is oxidized with 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone to the Schiff's base; hydrolysis gives the ketone (eq 2).8 This is not applicable to aliphatic ketones.
Condensation of ethoxymethyleneaniline with a-lithioalkylphosphonates gives, after treatment with Lithium Diisopropylamide, lithio enaminoalkylphosphonates, which condense with aldehydes to give a,b-unsaturated a-substituted aldehydes in moderate yield (eq 3).9
Treatment of a-substituted aliphatic acid chlorides with ethoxymethyleneaniline in the presence of Triethylamine generates only trans 1-phenyl-3-substituted 4-ethoxy-b-lactams in moderate to good yield.10,11 The chromium carbene complex in eq 4 photochemically cyclizes with the imidate to give the same azetidinone (X = NBz2) in good yield.12
Steven J. Brickner
The Upjohn Company, Kalamazoo, MI, USA