Eschweiler—Clarke reaction

A modified protocol of the Eschweiler-Clarke reaction, a reductive transamination, was also used for an efficient N-alkylation of hexahydroazepine and benzylamine in the presence of formic acid and aldehydes or ketones53. 

Torchy, S. and Barbry, D., N-alkylation of amines under microwave irradiation modified Eschweiler-Clarke reaction, /. Chem. Res. (S), 2001, 292-293. 

The first reported ferroceno heterocyclic compound of the type 1 was A-methyltetrahydropyridoferrocene (4). This compound was obtained from an anomalous Leuckart-Eschweiler-Clark reaction of 2-aminomethylferrocene (5 R = H), formaldehyde, and formic acid,4 although the structure 4 was not immediately recognized for this compound.5-8 The heterocyclic compound 4 can be used as an entry to 1,2-disubstituted ferrocenes since on reaction with potassium amide in liquid ammonia7 or with potassium hydroxide in methanol9 its... 

It is usually straightforward to poly-A-acylate or A-alkylate an aza crown. For example A-methylation of ring secondary amines is conveniently achieved using the Eschweiler-Clarke reaction involving condensation of the... 

Methylation of 3-piperideines can be performed by the Eschweiler-Clarke reaction (treatment with formaldehyde in the presence of excess formic acid).54... 

Other N-methylations of l-[cyano-(4-methoxyphenyl)-methyI]cyclohexanol using formaldehyde, formic acid, and excess water by a modified Eschweiler-Clarke reaction are described (3). 

The reductive methylation of amines with formaldehyde in the presence of formic acid. See Lindeke, B., Anderson, B., and Jenden, D.J., Specific deuteromethylation by the Eschweiler-Clark reaction. Synthesis of differently labelled variants of trimethylamine and their use of the preparation of labelled choline and acetylcholine, Biomed. Mass Spectrom. 3, 257-259, 1976 Boldavalli, E, Bruno, O., Mariani, E. et al.. Esters of A-methyl-iV-(2-hydroxyethyl or... 

Methylation of amines. The classical method for methylation of primary or secondary amines is the Eschweiler -Clarke reaction. The reaction involves treatment of an amine with formaldehyde and formic acid ... 

Eschweiler-Clarke reaction The reductive methylation reaction of an amine with methanal and methanoic acid to give the A-methyl derivative. 

The deuterated chelating agent iso-HMTT-di8, N[CH2CH2N(CD3)]3, was prepared from tris-(2-aminoethyl) amine, paraformaldehyde-d2, formic acid-d2 and D20 via the Eschweiller-Clarke reaction (7). 

The tetramethylcyclohexanediamine isomers, Compounds 12 and 13 in Table I, occurred admixed with at least three other components in the technical grade samples used. Except for the TMCHD isomers, some or all of the remaining compounds in Table I are found in differing amounts in the various N-permethylated polyethylene polyamine fractions (6,7). Experimentally the N-permethylated amines were obtained via the Eschweiler-Clarke reaction (16). 

The Eschweiler-Clarke reaction is the reductive methylation of amines 1, both primary and secondary, using formaldehyde (2) and formic acid (3).1 2 This represents a specific application of the Leuckart-Wallach reaction. 

In contrast to other methods for the methylation of primary amines, for example, the use of methyl iodide, this method leads to good yields of the iV,iV-dimethyl tertiary amines, without the formation of quaternary salt products.3 In comparison to reductive animation techniques, the reagents for the Eschweiler-Clarke reaction are cheap, and the reaction is easily scaled up.4... 

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