Reaction of 3-chloro-1-(2,4,6-trimethylphenyl)propan-2-one with amines

Abstract

SHORT COMMUNICATIONSWhile continuing our studies in the fields of synthesis and transformations of 1,2-chlorohydrins [1] obtained by reaction of arenes with 3-chloro-1,2-epoxypropane in the presence of aluminum chloride, we performed oxidation of 3-chloro-1-(2,4,6-trimethylphenyl)propan-2-ol (I) with chromium(VI) oxide and isolated 3-chloro-1-(2,4,6-trimethylphenyl)propan-2one (II). α-Chloro ketone II was brought into reaction with various primary amines in aqueous potassium hydroxide at room temperature. The reaction time was 20-45 min. Regardless of the amine nature, in all cases the products were the corresponding N-substituted 3-(2,4,6-trimethylphenyl)propionamides III-IX which were isolated in 50-97% yield as colorless crystalline substances and were recrystallized from ethanol.

1-(Piperidin-1-yl)-3-(2,4,6-trimethylphenyl)propan-2-ol

“…A recent study reported the reaction of 1-chloro-3-(2,4,6-trimethylphenyl)propan-2-one and primary amines. The chlorine atom in the α-chloro ketone is not replaced directly by the amino RNH-group; the intermediate product undergoes a Favorskii rearrangement that furnishes a compound having two methylene groups between the aromatic system and the amido unit (Yadigarov et al, 2010). A recent study used thiourea as the amino reactant (Maharramov et al, 2011).…”

“…For background to the synthesis: see: Yadigarov et al (2010). For the structure of tolperisone hydrochloride, see: Tanaka & Hirayama (2007).…”

4-(2,4,6-Trimethylbenzyl)-1,3-thiazol-2-amine

“…The chlorine atom in the α-chloro ketone is not replaced directly by an amino RNH-group. The intermediate product undergoes a Favorskii rearrangement that furnishes a compound having two methylene groups between the aromatic system and the amido unit (Yadigarov et al, 2010). The present study employs thiourea as the amine.…”

1-Methylamino-3-(2,4,6-trimethylphenyl)propan-2-ol

“…For background to the synthesis: see: Yadigarov et al (2010). For the structure of 1-(piperidin-1-yl)-3-(2,4,6-trimethylphenyl)propan-2-ol, see: Maharramov et al (2011).…”

“…A recent study reported the reaction of 1-chloro-3-(2,4,6-trimethylphenyl)propan-2-one and primary amines. The chlorine atom in the α-chloro ketone is not replaced directly by the amino RNH-group; the intermediate product undergoes a Favorskii rearrangement that furnishes a compound having two methylene groups between the aromatic system and the amido unit (Yadigarov et al, 2010). A recent study used cyclic secondary amine as the amino reactant in the synthesis of a compound having a formulation similar to that of tolperisone (a piperidine derivative that is commercially used as a muscle relaxant) (Maharramov et al 2011).…”