Regioselective N‐Alkylation of 2‐Aminoimidazoles with Alcohols to 2‐(N‐Alkylamino)imidazoles Catalyzed by the [Cp*IrCl₂]₂/K₂CO₃ System

Abstract

The direct N‐alkylation of 2‐aminoimidazoles to give the corresponding 2‐(N‐alkylamino)imidazoles was accomplished using alcohols as alkylating agents in the presence of a [Cp*IrCl2]2/K2CO3 system. The iridium‐catalyzed regioselective reaction is simple, efficient, general, and environmentally benign.

Substitution of alcohols by N-nucleophiles via transition metal-catalyzed dehydrogenation

“…The [Cp*IrCl 2 ] 2 /K 2 CO 3 catalyst system worked very efficiently for the regioselective N-alkylation of 2-amino-imidazoles 65 with alcohols, forming 2-(N-alkylamino)-imidazoles 66 (eqn ( 22)). 65 A catalytic amount of the relatively weak K 2 CO 3 base (10 mol%) was necessary, rendering the synthetic reactions highly selective.…”

Recent Advances in Iridium-Catalyzed Alkylation of C–H and N–H Bonds

“…Dehydrative alkylation using alcohols is also a common protocol for the synthesis of N-alkylated amines. − In 2009, Kempe used a P,N-ligand-coordinated iridium complex as an efficient catalyst for the selective monoalkylation of (hetero)aromatic amines (Scheme ) . This reaction proceeded under mild reaction conditions, and nearly quantitative conversion was observed at 70 °C, with a catalyst loading as low as 0.05 mol % iridium.…”

Sodium Hydroxide Catalyzed N-Alkylation of (Hetero) Aromatic Primary Amines and N1,C5-Dialkylation of 4-Phenyl-2-aminothiazoles with Benzyl Alcohols

“…In this regard, many groups have achieved N-alkylation of amines with alcohols using transition-metal/metal complexes as catalysts through borrowing hydrogen methodology. 9 In addition to these recent advancements, a major drawback of these methods is the requirement of transition-metal catalysts to promote this transformation efficiently. Thus, transition-metal separation from organic products is of particular importance for the synthesis of pharmaceutical fine chemicals because their residual toxicity in the target compounds is a central issue to consider; hence, the development of more improved synthetic routes without transition metals is desirable.…”

“…The C–N bond-forming reactions have attracted much attention over the last two decades and have found its applications in all areas of organic chemistry, ranging from the laboratory bench to the synthesis of pharmaceutical fine chemicals and the production of bulk chemicals. − Among the C–N bond forming reactions, the N -alkylation of primary amines is important because of the tremendous utility of these amines in industry for the synthesis of dyes, additives, agrochemicals, functional materials, and pharmacophores for the synthesis of bioactive molecules. − Arguably, the direct N -alkylation of amines with alcohols is most desirable because of the ready and inexpensive availability of wide range of alcohols and theoretically produces only water as a byproduct. In this regard, many groups have achieved N -alkylation of amines with alcohols using transition-metal/metal complexes as catalysts through borrowing hydrogen methodology . In addition to these recent advancements, a major drawback of these methods is the requirement of transition-metal catalysts to promote this transformation efficiently.…”