Primary Benzylamines by Efficient N-Alkylation of Benzyl Alcohols Using Commercial Ni Catalysts and Easy-to-Handle Ammonia Sources

Abstract

Primary benzylamines are highly important building blocks in the pharmaceutical and polymer industry. An attractive catalytic approach to access these compounds is the direct coupling of benzyl alcohols with ammonia via the borrowing hydrogen methodology. However, this approach is usually hampered by a series of side-reactions, one of the most prominent being the overalkylation of the formed primary amine. Herein, we describe a robust catalytic methodology, which utilizes commercially available heterogeneous Ni catalysts and easy-to-handle ammonia sources, such as aqueous ammonia or ammonium salts, for the formation of primary benzylamines with good selectivity and scope. Notably, our method enables the conversion of potentially lignin-derived vanillyl alcohol to vanillylamine, which can be used to produce emerging biobased polymers or as pharma building blocks. Important sugar derived platform alcohols as well as long chain aliphatic primary alcohols can be successfully aminated. Moreover, we provide an alternative, sustainable route to p-xylylenediamine and m-xylylenediamine, important components of heat resistant polyamides such as Kevlar.

Deoxygenation of Primary Amides to Amines with Pinacolborane Catalyzed by Ca[N(SiMe3)2]2(THF)2

“…Amines are widely present in natural products, pharmaceuticals, and agrochemicals. − Because of their importance, many synthetic strategies such as reductive amination, , alcohol amination, − and transamination, , and hydroamination , have been developed for the construction of complex amine architectures. One favored way to obtain amines is to deoxygenatively transform amides, which are prevalent in nature and synthetically accessible, into amines .…”

Direct Amination of Isohexides via Borrowing Hydrogen Methodology: Regio‐ and Stereoselective Issues

“…Due to a lack of diastereoselectivity, a mixture of the two amino‐alcohols was obtained . More recently, Barta et al also reported the mono‐amination of isosorbide using a supported‐Ni catalyst and aqueous ammonia within 32 to 51 % GC yield but without information concerning the stereochemistry . We thus developed the first synthesis of this pure chiral amino‐alcohol 7 in 54 % over 2 steps from isosorbide with an excellent optical purity (Scheme ).…”

Rapid Multialkylation of Aqueous Ammonia with Alcohols by Heterogeneous Iridium Catalyst under Simple Conditions

“…Water‐soluble iridium complex catalysts bearing N‐heterocyclic carbene ligands that enable the selective N‐monoalkylation of aqueous ammonia with a variety of alcohols were developed [26] . Meanwhile, heterogeneous catalysts using Ir, [28] Ni, [29–34] Ru, [35–37] Au−Pd, [38] and Rh‐In [39] have newly emerged. Nevertheless, there are still some restrictions in the catalytic reactions such as indispensability of organic solvent, high‐pressure atmosphere of hydrogen or ammonia, and high temperature.…”