Preparation and Utility of Trihaloethyl Imidates: Useful Reagents for the Synthesis of Amidines

Abstract

2,2,2-Trifluoro- and trichloroethyl imidates, which are easily prepared by reaction of a nitrile and a trihaloethanol in the presence of HCl, have proven to be excellent reagents for the preparation of amidines under mild reaction conditions. Depending on the nature of the amine nucleophile, the imidates can react either as the free-base or the hydrochloride salt in a telescoped process. In several cases, the p-bromobenzoate salt of the desired product was directly isolated from the reaction mixture.

Facile N-arylation of amidines and N,N-disubstituted amidines

“…N-Arylamidines have been prepared by reaction of aniline with corresponding thioimidic esters, 7a activated nitrile, 7a-d and trihaloethyl imidates. 8 Recently, application of transition-metal catalyzed C-N cross-coupling to N-arylation of amidines has been advanced. 9 On the other hand, tertiary amidines are generally prepared from monosubstituted amides or thioamides.…”

Synthesis of quinazolines and quinazolinones via palladium-mediated approach

“…Examples are deoxyvasicinone isolated from Adhatoda vasica, rutecarpine isolated from Evodia rutaecarpa , luotonin A isolated from Peganum nigellastrum , and tryptanthrin isolated from Couropita guianensis [53] . There are several approaches developed for the synthesis of ring-fused quinazolinones [53,54] substituted amidines [49] . There have been several recent reports of successful amidine N -arylation, particularly using copper catalysis [50] .…”

Strategy for Synthesizing Novel Acetamidines as CO2-Triggered Switchable Surfactants via Acetimidates

“…Amidines can be synthesized using various strategies, such as the nucleophilic addition of amines to nitriles [23], reaction of catalytic three-component coupling [24], displacement reaction of imidates with amines [25,26], and the Scoggins procedure [27,28]. Of these synthetic methods, the Scoggins procedure involving primary amines and N,N-dimethylacetamide dimethyl acetal can synthesize long-chain aliphatic amidines and aromatic amidines with a high yield of 90% accompanied by the formation of a small amount of imidates as a by-product [27,28].…”