The development of a sustainable catalytic reductive amination process

Abstract

The development of more sustainable catalytic reductive amination processes for the generation of high value amines represents a high priority challenge. An alternative cleaner route for the selective production of an amino acid (Tert-butylglycine, TBG) from a a-keto-carboxylic acid (Trimethylpyruvic acid TMP) under mild reaction conditions has been investigated. TMP was reacted with aqueous NH3 and hydrogen gas under atmospheric pressure at 343 K over commercial Pd/C, Pt/C, Rh/C and Pd/Al2O3 catalysts. Catalyst characterization in terms of temperature programmed reduction (TPR), H2 chemisorption, X-ray diffraction (XRD), transmission electron microscopy (TEM), BET area/pore volume and pH point of zero charge (pHpzc) measurements is provided and correlated with catalytic activity and selectivity. Mass transport contributions during reaction in a three phase slurry reactor were evaluated experimentally by varying (i) hydrogen flow rate, (ii) stirring speed, (iii) catalyst concentration and (iv) temperature. Reaction conditions wherein chemical control prevailed were established. Reductive amination rate was pressure invariant over the 1-20 bar range. Process optimisation revealed that the rate was sensitive to solution pH and NH3/TMP ratio. An increase in pH (with NaOH addition) above the pKa of ammonia was shown to elevate reaction rate. The basic character of the aminating agent also influenced rate as demonstrated by a comparison of activity using ammonium hydroxide, ammonium acetate and ammonium nitrate. Catalyst reuse was examined where a decline in activity was observed and is linked to pore occlusion and metal sintering. Solvent (water, 1-propanol, 1-butanol and aqueous mixtures of 1-propanol/1-butanol) effects were established where, in absence of mass transport limitations, reaction in pure 1-butanol delivered higher rate, a response that is attributed to combined TMP solubility and ammonia solvation. With the goal of probing reaction mechanism, the amination of two additional a-keto-carboxylic acids (pyruvic acid and phenylpyruvic acid) were screened where steric hindrance due to the substituent resulted in lower reaction rate.