Reductive Alkylation of Primary Amines with Carbonyl Compounds

2 REDUCTIVE ALKYLATION OF PRIMARY AMINES WITH CARBONYL COMPOUNDS 

Winans and Adkins obtained IV-butylcyclohexylamine (eq. 6.8) and N-butylpiperidine in 91 and 93% yields, respectively, by hydrogenating a mixture of cyclohexylamine or piperidine with slightly molar excess of butyraldehyde over Ni-kieselguhr at 125°C and 10 MPa H2.26 Under similar conditions hydrogenation of 

Raney Ni and copper-chromium oxide can be used satisfactorily for these reductive alkylations at elevated temperatures and pressures in ethanol solution or without a solvent (eq. 6.11). 2-pnm-Alkylaminoethanols were prepared in a similar manner in 60-90% yields by hydrogenating mixtures of aldehydes with ethanolamine. In these cases the alcohol solution of ethanolamine was cooled in ice while the aldehyde (15% molar excess) was added slowly in order to avoid polymerization. 

Emerson and Waters alkylated primary aromatic amines with C2-C7 aliphatic aldehydes and benzaldehyde over Raney Ni in the presence of sodium acetate as a condensing agent and obtained /V-alkylanilincs in 47-65% yields.33 With C2-C5 aldehydes, up to 10% of the tertiary amines were produced, but no tertiary amines were found in the case of heptanal and benzaldehyde. With acetaldehyde in the absence of sodium acetate, aniline was recovered unchanged over platinum oxide and a mixture of amines resulted over Raney Ni, compared to 41 and 58% yields of N-ethylaniline over platinum oxide and Raney Ni (eq. 6.12), respectively, in the presence of sodium acetate. 

Similarly, (V-ethyl-l-naphthylamine was prepared in 88% yield, and (V-ethyl-, N-bu-tyl- and (V-benzyl-2-naphthylamine, and (V-ethyl- and (V-butyl-/ -toluidine were prepared in 50-64% yields.34 In the alkylation of / -toluidine and / -anisidine with butyraldehyde, N,N-dibutyl derivatives were also produced in 19 and 25% yields, respectively. The Emerson-Waters procedure was also applied to the reductive alkylation of 2-phenylpropylamines and 2-phenylisopropylamines with C1-C3 aldehydes (amine aldehyde ratio = 1 3).35 With higher aldehydes the monosubstituted products were isolated in good yields (in 48-94% yields with acetaldehyde), while with formaldehyde (V.N-dimethyl derivatives were obtained in 51-85% yields. 

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