Reductive Amination

Reductive amination describes the process of adding ammonia to a carbonyl compound to produce a more substituted amine. Variations include the use of either ketones or aldehydes as the carbonyl-containing species.

Reductive Amination

The first step for either reductive amination or reductive alkylation is the reversible formation of the imine intermediate and water. The imine is then hydrogenated to the amine.

Another variation is the apparent direct amination of alcohols. This reaction can be more thoroughly described as progressing via dehydrogenation of the alcohol to a ketone (or, in the case of a primary alcohol, to an aldehyde). The carbonyl-containing compound next reacts with ammonia or an amine to form the imine, which is hydrogenated to the amine.

Reductive amination describes the process of adding ammonia to a carbonyl compound to produce a more substituted amine. Variations include the use of either ketones or aldehydes as the carbonyl-containing species.

Why it's not that simple

There are many opportunities for these reaction sequences to go awry.

First, the carbonyl compound may not react completely with the amine (including ammonia), and may simply be reduced to the alcohol. Another opportunity for byproduct formation comes from the addition of the product amine to the imine, and following loss of ammonia, a dimer-like product results:

addition of the product amine to the imine, and following loss of ammonia, a dimer-like product results

Note that formation of the dimer-like product may be the desired reaction! The choice of catalyst, operating conditions and molar quantities of certain reactants will influence the selectivity. When high yields of mono-aminated products are desired, excess ammonia or amine is used; often times a Full Morris or more is required for >90% selectivity

What Pressure Chemical Company has to get the job done

High pressure reactors. High pressure autoclaves are available from the laboratory scale to 250 gallons. Depending on choice of solvent (which may be the amine or ammonia!) and reaction temperature, pressures vary from below 100 to over 1,000 psi.

Amine/ammonia delivery systems. Where gaseous amines are used, transfer systems must be considered. And in some cases, the carbonyl compound is added to the amine in the pressurized system to influence selectivity. High pressure feed pumps are used to add the carbonyl compound at a controlled rate.

Amine/ammonia scrubbing systems. The job is not over when the reaction is complete. The excess amine/ammonia must be separated from the crude mixture. In large, commercial systems these materials are cryogenically trapped and reused in subsequent batches. PCC manages the excess by use of absorbers and neutralizers at all scales.

Purification of the crude product. Distillation is a common technique for purifying the crude product of a reductive amination. The common impurities (alcohol, dimer etc) will often have a large enough difference in boiling point to make distillation a good option.

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