Leuckart reaction Eschweiler-Clarke modification

Eschweiler-Clarke modification org chem A modification of the Leuckart reaction, involving reductive alkylation of ammonia or amines (except tertiary amines) by formaldehyde and formic acid. esh,vTl-3r klark. mad-o-fo ka-shon ... 

The reactions of the completely reduced compounds have attracted much attention because of their close relationship to piperazine. Thus it has been shown, as might be expected, that the 2-position in compounds such as the parent 100 can be readily acetylated and benzoylated" and ureas are formed with phenylisocyanate and phenylisothiocyanate." Compound 100 also reacts at the 2-position with p-acetamidobenzene-sulfonyl chloride to give a sulfonamide. There are several examples of the alkylation of the amine in the 2-position. Various alkyl halides -have been used, as well as ethylene oxide," p-nitrobenzoyl-ethyleneimine, " and l-guanyl-3,5-dimethylpyrazole nitrate. Compound 100 also undergoes the Eschweiler-Clarke modification of the Leuckart reaction to give the 2-methyl compound." ... 

As an example of all lation, methylation by the Eschweiler-Clarke modification of the Leuckart reaction was adopted. The methylation of the cyclic amines was carried out without difficulty by only refluxing the mixture of the amine, 37% formalin and 95% formic acid. 

N,N, N, N -Tetramethyl-2,ll,20,29-tetraazaC3.3.3.3]paracyclophane (lVIe N [3 ]PC) Methylation of the tetramine by the Eschweiler-Clarke modification of the Leuckart reaction ... 

D. Eschweiler-Clarke Modification of the Leuckart Reaction 13-10. Preparation of l-Methyl-2-(p-tolyl)piperidine... 

Leuckart reaction, 130-131 Eschweiler-Clarke modification, 131-132 Lossen rearrangement, 108... 

A modification of the Leuckart reaction for the preparation of methylated amines which requires less drastic reaction conditions, known as the Eschweiler-Clarke reaction, involves the use of aqueous formaldehyde and an excess of formic acid as reducing agent, along with the appropriate amine. Usually the reaction conditions... 

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