Synthesis and Crystal Structures of Stable 4-Aryl-2-(trichloromethyl)-1,3-diaza-1,3-butadienes

Abstract

A simple and convenient method to generate 4-aryl-substituted 1H-2-(trichloromethyl)-1,3-diaza-1,3-butadienes from aryl(chloro)methaniminium salts (best known as Vilsmeier-Haack reagents) and trichloroacetamidine has been developed. These 4-aryl-1H-1,3-diazabutadienes are isolable, relatively stable during silica gel chromatography, and can be crystallized. The analysis by X-ray diffraction demonstrated that in the solid state these 1,3-diazabutadienes have an s-cisoid conformation. The principal characteristic of these 1,3-diazabutadienes is their reactivity towards electron-deficient acetylenes, reacting under mild reaction conditions to produce 4-aryl-2-(trichloromethyl)pyrimidines in good yields.

Nitrene Cyclization of 2-(Trichloromethyl)-5-phenylpyrimidines: Application to the Synthesis of 2-(Trichloromethyl)pyrimido[4,5-b]indoles and Related Heterocycles

“…Over the past years, our research group has devoted great efforts on the synthesis of trichloromethylated heterocyclic compounds using 2-(trichloromethyl)-1,3-diazabutadienes as the source of the trichloromethyl group. [47][48][49][50][51] Based on our interest in the synthesis of 2-(trichloromethyl)pyrimidine derivatives and their potential application in medicinal chemistry, we were curious to explore the specific reactivity of 4-chloro-5-phenyl-2-(trichloromethyl)pyrimidines with the azide ion. These types of derivatives might undergo cyclization reactions by the loss of N 2 through a nitrene species which reacts onto the ortho position of the attached phenyl substituent at C-5 of the pyrimidine ring, that acts as an acceptor of the nitrene species, to afford pyrimido [4,5-b]indole derivatives containing the trichloromethyl unit.…”

“…Our approach began with the synthesis of the necessary 4-chloro-5-phenyl-2-(trichloromethyl)pyrimidines 1a-1c which were prepared from 2-(trichloromethyl)-1,3-diazadienes according to our published procedure. [48][49][50][51] Briefly, a solution of the respective 2-(trichloromethyl)-1,3-diazadiene in dichloromethane was reacted with phenylacetyl chloride under basic conditions (Et 3 N/DMAP) at -10 °C and warmed to room temperature. The crude material obtained was treated with POCl 3 and refluxed in toluene solution to afford the 4-chloro-5-phenyl-2-(trichloromethyl)pyrimidines 1a-1c (Scheme 1).…”

“…The 6-substituted 4-chloro-5-phenyl-2-(trichloromethyl)pyrimidines 1a-1c were prepared according to our published procedure. [48][49][50][51] 6-Substituted 4-Azido-5-phenyl-2-(trichloromethyl)pyrimidines 2a-2c; General Procedure NaN 3 (5.0 equiv) was added to a solution of 6-substituted 4-chloro-5phenyl-2-(trichloromethyl)pyrimidine 1 (1.0 equiv) in anhydrous DMF (10 mL/mmol 1) under N 2 atmosphere. The reaction mixture was stirred at rt for 15 h. After completion, the reaction mixture was washed with sat.…”