[67242-59-5]  · C7H8N2O  · N-Methyl-N-(2-pyridyl)formamide  · (MW 136.17)

(formylating reagent for Grignard reagents1 and certain organolithiums;6 sequential addition of two Grignard reagents can provide unsymmetrical secondary alcohols3)

Alternate Name: 2-(N-formyl-N-methyl)aminopyridine.

Physical Data: bp 71-72 °C/0.05 mmHg; d 1.137 g cm-3.

Form Supplied in: colorless liquid; commercially available.

Analysis of Reagent Purity: IR, NMR.

Handling, Storage, and Precautions: moisture sensitive; irritant; should be kept under argon or nitrogen.

General Discussion.

N-Methyl-N-(2-pyridyl)formamide (1) is a good formylating reagent for certain organometallics. Dropwise addition of Grignard reagents to (1) provides good yields of aldehydes (eq 1).1

Various Grignard reagents have been studied and yields are good to excellent. The formylation is effective and facile because of a six-membered chelate complex formed in situ; this inhibits further reaction at low temperature (eq 2).1,2 On workup with aqueous acid the complex is protonated and dissociates to give the aldehyde and amine salt. The aldehyde is isolated by ether extraction, and the byproduct, 2-(methylamino)pyridine, can be recovered by neutralization of the aqueous layer with sodium hydroxide and extraction with CH2Cl2. The amine can be economically recycled to (1) in 90% yield by formylation with a formic acid-acetic anhydride mixture.3

Using a modification of this methodology, unsymmetrical secondary alcohols can be synthesized via a one-pot reaction using two different Grignard reagents (eq 3).3 Similarly, the vinyl Grignard reagent (2) has been formylated using the reagent (1) (eq 4).4

Using a one-pot reaction, a dithioester has been converted to a protected a-keto carbaldehyde using the reagent (1) (eq 5).5 Heterocycles can be converted to their formyl derivatives by lithiation and reaction with (1) (eq 6).6 The importance of the reagent (1) has been demonstrated by its application in natural product synthesis.7

Related Reagents.

N,N-Dimethylformamide; N-Formylpiperidine; N-Methylformanilide.

1. Comins, D. L.; Meyers, A. I. S 1978, 403.
2. Amaratunga, W.; Frechet, J. M. J. TL 1983, 24, 1143.
3. Comins, D. L.; Dernell, W. TL 1981, 22, 1085.
4. Munstedt, R.; Wannagat, U. LA 1985, 944.
5. Meyers, A. I.; Tait, T. A.; Comins, D. L. TL 1978, 4657.
6. Pridgen, L. N.; Shilcrat, S. C. S 1984, 1048.
7. (a) Meyers, A. I.; Comins, D. L.; Roland, D. M.; Henning, R.; Shimizu, K. JACS 1979, 101, 7104. (b) Meyers, A. I.; Roland, D. M.; Comins, D. L.; Henning, R.; Fleming, M. P.; Shimizu, K. JACS 1979, 101, 4732. (c) Guthrie, A. E.; Semple, J. E.; Joullie, M. M. JOC 1982, 47, 2369.

Daniel L. Comins & Sajan P. Joseph

North Carolina State University, Raleigh, NC, USA

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