Metal-Free Synthesis of Guanidines from Thioureas in Water Reactions Mediated by Visible Light

Abstract

Metal-free synthesis of guanidine from thiourea under visible light irradiation in water was successfully developed. Using 1-5% mol of inexpensive and commercially available phenazine ethosulfate as a photocatalyst in the presence of 1% CTAB as surfactant with K2CO3 as an additive base, transformations of a variety of thiourea into corresponding guanidine under visible light irradiation were achieved in moderated to high yields. The advantages of this reaction included the use of metal-free photocatalyst, water as a non-toxic solvent and ease for operating at room temperature in open-flask manner.

Electrochemical NaI-mediated one-pot synthesis of guanidines from isothiocyanates via tandem addition-guanylation

“…Based on the experimental results and previous reports, 19,22,24 we proposed two plausible mechanisms of the addition-guanylation as shown in Scheme 5 (pathways A and B). Firstly, the intermediate thiourea 1aa was generated in situ through the addition of aniline 2a to isothiocyanate 3a , and was tautomerized-deprotonated under basic conditions to produce 1aa′ .…”

“…The desul-furization of 1aa″ was facilitated by those iodide oxidizing species to generate carbodiimide (5aa). [22][23][24] Then the guanylation occurred to produce the desired product 4aab via the addition of amine to 5aa. Although the exact mechanism of direct electrolysis remains unclear, we also postulated a tentative pathway for the direct electrochemical process.…”

“…In recent years, our group and Zhang's group first reported the use of a photocatalyst as a desulfurizing agent in guanidine synthesis. [22][23][24] Ru(bby) 3 Cl 2 , 22 dipyrido purine, 23 and phenazine ethosulfate 24 could be used in catalytic amounts to perform the guanylation between thioureas and amines mediated by visible light at ambient temperature in aqueous media. Although these methods offer wide functional group tolerance, high efficiency, and mild synthetic routes of guanidines, there are some concerns that need to be addressed.…”

Recent advancement in the synthesis of isothiocyanates

“…Several methods have been explored to broaden the substrate scope of electron-deficient anilines and aminopyridines. 55,[57][58][59][60][61]67,71,72,74,75 Moreover, employing a strong base, 69 ball milling, 56 a photoredox catalyst, 72 an electrolytic reaction, 73 or an appropriate desulfurization reagent 60,61,68,71 enables the one-step synthesis of isothiocyanates. Table 1 provides a comprehensive review of the progress in dithiocarbamate salt protocols over the past decade.…”

Electrocatalytic Desulfurizative Amination of Thioureas to Guanidines

“…Among the existing synthetic routes to substituted guanidines, coupling of amines with thioureas is highly promising because of the stable, cost-effective, and readily accessible thiourea reactants . Previous reported approaches to guanidines from thioureas involved treatment with various desulfurizing agents, including metal salts, trichloro cyanuric acid, Burgess’s reagent, Mukaiyama’s reagent, hypervalent iodine, and oxygen . However, these methods lead to some limitations such as the use of toxic metals, stoichiometric amounts of oxidants, relatively harsh conditions, or a limited substrate scope.…”