Amines by reductive amination

A valuable application of sodium cyanoborohydride is in the synthesis of amines by reductive amination. What combination of carbonyl and amine components would give the following amines by this method ... 

Oxidation aldehydes ketones acids 10 amines by reductive amination 8... 

Mechanism 19-6 Diazotization of an Amine 910 19-17 Reactions of Arenediazonium Salts 911 Summary Reactions of Amines 915 19-18 Synthesis of Amines by Reductive Amination 918 19-19 Synthesis of Amines by Acylation-Reduction 920... 

Many aldehydes (RCHO) and ketones (R2CO) are converted into amines by reductive amination reduction in the presence of ammonia. Reduction can be accomplished catalytically or by use of sodium cyanohydridoboratc, NaBHjCN. Reaction involves reduction of an intermediate compound (an imine RCH NH or R2C NH) that contains a carbon-nitrogen double bond. 

Assembly of Diels-Mder reaction components using a Ugi reaction Furfural and related compounds (293) can serve as diene building blocks in intramolecular and intermolecular cycloadditions, as they can be attached to resin-bound amines by reductive amination [306]. Particularly versatile is the use of furfural derivatives in 4-component Ugi reactions, where the diene and the dienophile component can be present. However, in the reaction set-up the electronic characteristics of the building blocks such as HOMO/LUMO energy or electron demand have to be considered to receive high yields. In the study presented by Schreiber et al., an acrylic acid served as dienophile (Scheme 64) [307]. 

Stevens chose to protect the aldehyde immediately after the Michael reaction to prevent side reactions on this reactive group, and to put in the amine by reductive amination (Chapter 8) using sodium cyanoborohydride as the reducing agent. Note the short cut of decarboxylation with NaCI in wet solvent (DMF or DMSO) when the ester, e.g. (13) is needed. 

Method for the production of amines by reductive amination of carbonyl componnds nnder transfer-hydrogenation conditions. Bdmer, A. Dingerdissen, U. Kadyrov, R. Riermeier, T. H. Tararov, V. Degussa AG, Germany. Patent pnbhcation number US2004267051, 2004. 

This useful way of adding two methyl groups to a primary amine by reductive amination is sometimes called the Eschweiler-Clarke reaction. For more on formic acid as a reducing agent, see Chapter 41,... 

Formyl-pinane can be isolated from the aldehyde mixture as pure compound in moderate yield by distillation with a column of 20 trays [70a]. In turn, the aldehyde was converted into the primary amine by reductive amination with ammonia. The chiral amine has been utilized, for example, for the optical resolution of racemic pantolactone. Alternatively, aldol condensation of the formed aldehydes with ketones and subsequent hydrogenation give alcohols that might have a broad scope of potential applications in perfumes, soaps, and shampoos [73]. 

Yields dropped notably, when this procedure was applied to synthesize branched polyamines. This comes from the slow reduction rate of the tertiary amide that leads mainly to only partially reduced side products, even after 5 days at 65 °C. The problem was satisfactorily solved for ahphatic substituents by alkylating the secondary amine by reductive amination with aldehydes using NaBHAcs as an additional hydride source. 

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