[93-61-8]  · C8H9NO  · N-Methylformanilide  · (MW 135.18)

(formylating reagent for certain organometallics;1 used in combination with POCl3 for Vilsmeier-Haack reactions2 and heterocycle syntheses3,4)

Alternate Name: N-methyl-N-phenylformamide.

Physical Data: mp 8-13 °C; bp 243-244 °C; d 1.095 g cm-3.

Form Supplied in: colorless liquid; widely available.

Analysis of Reagent Purity: IR, NMR.

Handling, Storage, and Precautions: irritant, toxic.

General Discussion.

N-Methylformanilide (1) has been used for formylating organolithium and Grignard reagents (eq 1).1

Alternatively, formylation can be achieved under Vilsmeier-Haack reaction conditions.2 In this manner, aromatic compounds such as (2) can be formylated by treatment with the chloromethylene ammonium salt generated from reagent (1) (eq 2).

1,3-Cyclohexanediones and vinyl acetates undergo some interesting transformations on reaction with (1) in the presence of Phosphorus Oxychloride (eqs 3 and 4).3 A wide variety of vinyl compounds other than vinyl acetate have been successfully utilized in this reaction (eq 4).3b

1,3,5-Triazines (3) can be obtained by condensing cyanoamidines with (1) and phosphorus oxychloride (eq 5).4 Enaminals can be afforded by the reaction of (1) with a vinyl ether and Oxalyl Chloride.5

A convenient synthesis of both symmetrical and unsymmetrical 1,5-diketones (4) has been achieved (eq 6).6

N-Acylamino-2-azaallene salts are the products of reaction of (1) with nitrilium salts.7 Enamines can be easily made by reacting metal carbene complexes with (1).8 Reduction of (1) to N,N-dimethylaniline can be effected using bis(2-bromoethylselenium dibromide) and sodium borohydride.9

Related Reagents.

N,N-Dimethylformamide; N-Formylpiperidine; N-Methyl-N-phenyl(chloromethylene)ammonium Phosphorochloridate; N-Methyl-N-(2-pyridyl)formamide.

1. (a) Talley, J. J.; Evans, I. A. JOC 1984, 49, 5267. (b) Azzena, U.; Melloni, G.; Piroddi, A. M.; Azara, E.; Contini, S.; Fenude, E. JOC 1992, 57, 3101. (c) Jacob, P. III; Shulgin, A. T. JMC 1983, 26, 746. (d) Amaratunga, W.; Frechet, J. M. J. TL 1983, 24, 1143.
2. (a) Yamamura, K.; Miyake, H.; Murata, I. JOC 1986, 51, 251. (b) Rizzacasa, M. A.; Sargent, M. V. JCS(P1) 1987, 2017. (c) Deschamps, E.; Mathey, F. JOC 1990, 55, 2494.
3. (a) Katritzky, A. R.; Marson, C. M.; Palenik, G.; Koziol, A. E.; Luce, H.; Karelson, M.; Chen, B. C.; Brey, W. T 1988, 44, 3209. (b) Meth-Cohn, O. TL 1985, 26, 1901. (c) Meth-Cohn, O. S 1986, 76.
4. Harris, R. L. N. AJC 1981, 34, 623.
5. Lee, G. T.; Amedio, J. C.; Underwood, R. Jr.; Prasad, K.; Repic, O. JOC 1992, 57, 3250.
6. Kiyooka, S.-I.; Yamashita, T. CL 1987, 1175.
7. Jochims, J. C.; Glocker, M. O. CB 1990, 123, 1537.
8. (a) Soderberg, B. C.; Hegedus, L. S. JOC 1991, 56, 2209. (b) Aumann, R.; Hinterding, P. CB 1990, 123, 611.
9. Akabori, S.; Takanohashi, Y. CL 1990, 251.

Daniel L. Comins & Sajan P. Joseph

North Carolina State University, Raleigh, NC, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.