Selective N,N-Dimethylation of Primary Aromatic Amines with Methyl Alkyl Carbonates in the Presence of Phosphonium Salts

Abstract

In the presence of onium salts, at 140-170 degrees C, methyl alkyl carbonates [1a-c, ROCO2Me, R = MeO(CH2)2[O(CH2)2]n; n = 2-0, respectively] react with primary aromatic amines (XC6H4NH2, X= p-OMe, p-Me, H, p-Cl, p-CO2Me, o-Et, and 2,3-Me2C6H3NH2) to yield the corresponding N,N-dimethyl derivatives (ArNMe2) with high selectivity (up to 96%) and good isolated yields (78-95%). Phosphonium salts (e.g., Ph3PEtI and n-Bu4PBr) are particularly efficient catalysts. Overall, a solvent-free reaction is coupled with safe methylating agents (1a-c) made from nontoxic dimethyl carbonate.

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

“…14e Notably, methanol could be used as substrate, affording mono‐ and bis‐alkylated amines with good yields ( 3 o and 3 p ) and thus providing a green and selective method for N ‐methylation of amines 24. The use of methanol as an alkylating reagent is rare in the literature7a,b and the selective formation of mono‐methylated amines is a still difficult issue in N ‐methylation reactions 24a,c–e. Secondary alcohols displayed lower activities, however, even with a higher catalyst loading and longer reaction time ( 3 q and 3 r ).…”

Sulfur and Nitrogen Mustard Carbonate Analogues

“…While being stirred magnetically, the mixture was heated at reflux temperature for 22 h. The reaction mixture was then filtered, and the solvent was evaporated. (1): [14] (6): [15] The pure compound was obtained by fractionated distillation under vacuum; b.p. 60-62°C (0.05 bar).…”

Phosphonium Salt Organocatalysis

“…[51] Selva et al employed unsymmetrical carbonates as methylating agents of primary aromatic amines in the presence of Lewis acidic ammonium and phosphonium salts, respectively. [52] Ethyltriphenylphosphonium iodide (17) proved to be a particularly efficient catalyst for the N,N-dimethylation of various substituted anilines (Scheme 18). At 170 8C the reaction times were short and the desired products were obtained in good to excellent yields and selectivities.…”