Grignard reagents reaction with formamides

Alkylation of enamines Addition of amines to triple-bond compounds Addition of amines to aldehydes or ketones Reaction between Grignard reagents and formamides Reaction of phosphonates with aldehydes or ketones... 

The reaction of Grignard reagents with orthoformates is an old-established alternative to reactions with formates (see Section 6.2) or formamides (see Section 6.3) for the preparation of aldehydes. Many examples are listed in General Ref. [A], and two are fully described in Organic Syntheses. ... 

Aldehydes can also be obtained from Grignard reagents by reaction with formamides, such as A-formylpiperidine. In this case, the initial adducts are stable and the aldehyde is not formed until hydrolysis during workup. 

An interesting appetite suppressant very distantly related to hexahydroamphetamines is somanta-dine (24). The reported synthesis starts with conversion of 1-adamantanecarboxylic acid (20) via the usual steps to the ester, reduction to the alcohol, transformation to the bromide (21), conversion of the latter to a Grignard reagent with magnesium metal, and transformation to tertiary alcohol 22 by reaction with acetone. Displacement to the formamide (23) and hydrolysis to the tertiary amine (24) completes the preparation of somantadine [6]. 

This type of reaction with A N-disubstituted formamides, giving aldehydes, was an early application of Grignard reagents, sometimes known as the Bouveault reaction [A]. Dimethylformamide and N-methylformanilide, PhN(Me)CHO, have been most commonly used, but more recently iV-formylpiperidine and 2-(/V-formylmethylamino)pyridine have been recommended examples are listed in Table 6.5, and a recent example of the traditional procedure follows. It should be noted that these reactions are subject to a number of side-reactions [A]. One useful one is the formation of enamines by elimination from the initial adduct [9] ... 

A few tertiary amines have been prepared from i T,iV-dialkyl-formamides by reaction with an excess of Grignard reagent, though yields are frequently not high (reaction 68)... 

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