A new and environmentally benign synthesis of aroylguanidines using iron trichloride

Abstract

A new synthetic approach for the guanylation of aroylthioureas using iron trichloride is presented.

Palladium(0)-Catalyzed Carbonylative One-Pot Synthesis of N-Acylguanidines

“…Light brown solid (116 mg, 78%). Compound 5r is known and spectral data were in agreement with the proposed structure and matched those reported in the literature …”

“…Acylguanidines are typically obtained from the reaction of thioureas and amines. However, this often requires the addition of mercury salts or coupling agents in order to achieve desulfurization. − Additionally, acylguanidines can be prepared from the condensation of aroyl- S -methylisothioureas with amines . Another approach is to prepare acylguanidines from N -cyanobenzamides, , which generally are prepared by reacting the corresponding acyl chloride and sodium cyanamide. − They have also been prepared via radical reactions including the rearrangement reaction of acylcyanamides and diphenyldisulfide followed by subsequent reaction with amines and the synthesis of polycyclic acylguanidines via a radical cascade cyclization reaction .…”

Iron Trichloride and Air Mediated Guanylation of Acylthioureas. An Ecological Route to Acylguanidines: Scope and Mechanistic Insights

“…Thus, in the case of guanidine 5a the yield was decreased by 26% (50% vs 76% yield) when 0.7 equiv of iron(III) chloride was used. 22 Taking one step back to the results of LC-MS analysis, we still needed to find an explanation for the formation of side products. In this regard it would be useful to determine at which point of the guanylation the exchange of aromatic rings occurs.…”

“…21 We recently published our results on the synthesis of aroylguanidines using iron(III) chloride as a green, highly reactive, and cost-efficient reagent for the conversion of thioureas. 22 Among a broad variety of synthetic approaches 1,23 toward the synthesis of acylguanidines, conversions starting from thioureas are frequently used. Thioureas are easily accessible and convenient to handle due to their high stability.…”

“…However, we were able to show that our approach using nontoxic and low-priced FeCl 3 grants access to N-benzoylguanidines in comparable or superior yields under mild reaction conditions using easily accessible and stable starting materials. 22 The aim of this publication is to highlight the role of iron(III) chloride in the desulfurization of thioureas using in situ IR spectroscopy and other analytical methods. The scope of the reaction and optimization of the synthetic protocol are discussed.…”