Alkylation of Amines with Alcohols and Amines by a Single Catalyst under Mild Conditions

Abstract

An efficient catalytic system for the alkylation of amines with either alcohols or amines under mild conditions has been developed, using cyclometallated iridium complexes as catalysts. The method has broad substrate scope, allowing for the synthesis of a diverse range of secondary and tertiary amines with good to excellent yields. By controlling the ratio of substrates, both mono- and bis-alkylated amines can be obtained with high selectivity. In particular, methanol can be used as the alkylating reagent, affording N-methylated products selectively. A strong solvent effect is observed for the reaction.

Hofmann N‐alkylation of aniline derivatives with alcohols using ferric perchlorate immobilized on SiO2 as a catalyst through Box–Behnken experimental design

“…[8] 3 Montmorillonite 1-30 39-99 1,4-Dioxane, 150°C [7] 4 Iridium complex/K 2 CO 3 12-24 19-95 2,2,2-Trifluoroethanol, 100°C [9] 5 Pd/Fe 2 O 3 2-28 72-99 Solvent-free, 140-170°C [10] 6 CsOH⋅H 2 O 2 4 -28 26-95 Solvent-free, air, 130-150°C [33] 7 Au/TiO 2 5-63 50-98 120°C, N 2 (5 atm), toluene [34] 8 P h 2 CHBr 24 Trace to 96 Solvent-free, N 2 , 120°C [35] A variety of aniline derivatives with electron-donating as well as electron-withdrawing groups undergo N-alkylation with isopropanol, α-phenylethanol and diphenylcarbinol derivatives using Fe(ClO 4 ) 3 /SiO 2 in good to excellent yields and in short reaction times.…”

“…[3][4][5] The most common route is N-alkylation of amines with alkyl halides which produces a mixture of amines and ammonium halides and leads to low selectivity and problems involving product separation and purification. [8][9][10] Ferric perchlorate is a transition metal Lewis acid that acts as an inexpensive, easily available, odourless, nontoxic, reusable and stable catalyst in many organic reactions. [6,7] Alkylation of amines with alcohols instead of alkyl halides is an environmentally friendly and efficient method for synthesizing N-substituted amines because water is the only by-product.…”

ChemInform Abstract: Pentamethylcyclopentadienyl Iridium(III) Metallacycles Applied to Homogeneous Catalysis for Fine Chemical Synthesis

“…Based on results relatedt oi mine reduction and dehydrogenation (see above), Xiao and co-workers reported the application of half-sandwichi ridium(III) metallacycles to catalyse amine al-kylationw ith alcohols or amines under rather mild conditions (Scheme13). [21] TFE was found to be crucial for the reactiont op roceed as no reaction was observed with any other solvent. Alkylation of anilines and cyclic amines could be performed with variousa lcoholsi ncluding methanol.…”

Pentamethylcyclopentadienyl Iridium(III) Metallacycles Applied to Homogeneous Catalysis for Fine Chemical Synthesis

“…Based on results related to imine reduction and dehydrogenation (see above), Xiao and co‐workers reported the application of half‐sandwich iridium(III) metallacycles to catalyse amine alkylation with alcohols or amines under rather mild conditions (Scheme ) …”