Synthesis of Mono- and N,N-Disubstituted Thioureas and N-Acylthioureas

Abstract

1-Benzotriazole-1-carbothioamide (2), prepared from 1-cyanobenzotriazole (1) and hydrogen sulfide, reacts with amines to give thioureas 3a-e. Reactions of (benzotriazol-1-yl)carboximidamides 4a-d,f-j and acyl-5a-f,i-k or arylaminocarbonyl-5g,h (benzotriazol-1-yl)carboximidamides with hydrogen sulfide give the corresponding thioureas 3a-d,f-j, and N-acylthioureas 6a-f,i-k or N-carbamoylthioureas 6g,h, respectively.Thiourea moieties are important chemical building blocks that have numerous chemical and pharmaceutical applications. For example, recent reports describe thiourea derivatives as efficient guanylating agents both in solution 1 and on solid support. 2 Thermal decomposition of N-arylthioureas gives aryl isothiocyanates. 3 Oxidation of arylthioureas with lead tetraacetate 4 or iodic acid 5 affords arylcyanamides. Thioureas condense with a-halocarbonyl compounds to afford 2-amino-1,3-thiazoles. 6 Benzothiazoles can be prepared from arylthioureas in the presence of bromine. 7 Solid-phase Biginelli pyrimidine synthesis 8 and synthesis of imidazolone derivatives 9 using resin-bound thioureas have been reported. The uses of thioureas to make 1,3-thiazines, 10 1,3-diazines, 11 1,3-quinazolines 12 and 1,2,4-triazines 13 were also described recently.Synthetic approaches to thioureas have been long investigated. 14 Well-known routes to substituted thioureas (Scheme 1) involve reactions of (i) anilines with sodium 15 or ammonium thiocyanate 16 in the presence of strong acids (TFA or concentrated HCl); (ii) aroyl isothiocyanates with amines followed by basic hydrolysis; 17 (iii) silicon tetraisothiocyanate with primary and secondary amines; 18 (iv) unsubstituted thioureas with primary alkyl amines at 170-180°C; 19 (v) isothiocyanates with ammonia or amines; 20 (vi) primary amines with carbon disulfide in the presence of mercury acetate and aqueous ammonia; 21 and (vii) disubstituted cyanamides with hydrogen chloride and LiAlHSH 22 or hydrogen sulfide in the presence of ammonia. 23 Mono and N,N-disubstituted thioureas were also prepared on solid support from Fmoc-isothiocyanate with subsequent deprotection. 9 Scheme 1Acylthioureas are valuable starting materials for numerous transformations: acylthioureas were used for the preparation of four-, 24 five-, 25 six-25c,26 and seven-27 membered heterocyclic ring systems. N,N-Dialkyl-N¢-acyl(aroyl)thioureas are efficient ligands for the separation and refinement of platinum group metals (Pd, Rh, Ru, Ir, and Os). 28 Acylthiourea derivatives have been patented as antidiabetic, 29 antiarthritic, 30 antineoplastic, 31 and anticoagulant 32 agents and for treatment of cognitive problems 33 and prostate disorder. 34 Herbicidal, 35 fungicidal, 35 bactericidal, 35 insecticidal 36 and plant growth regulator activities have also been reported.Common routes to acylthioureas are presented in Scheme 2. Acylthioureas can be prepared by (i) reaction of aminothiocarbonylimidoyl chlorides with potassium thiocyanate followed by hydrolysis; 37 (ii) acylation of N,N-disubstituted thioureas; 38 (...

N,N-Disubstituted-N′-acylthioureas as modular ligands for deposition of transition metal sulfides

“…The N,N-disubstituted-N′-acylthiourea ligands are readily synthesized in a two-step, one-pot reaction by mixing the acid chloride and sodium thiocyanate, followed by addition of the secondary amine (Scheme 1). 32 After purification by recrystallization from an appropriate solvent mixture, the ligand was deprotonated with a mild base and reacted with a metal salt to form the respective ML 2 or ML 3 complex in good yield. 33 The wide range of commercially available acid chlorides and secondary amines make this family of ligands highly modular.…”

Synthesis and phytotoxic activity of novel acylthiourea and 2H-1,2,4-thiadiazolo[2,3-.ALPHA.]pyrimidine derivatives

“…General procedure for synthesizing compounds 4a-4h 22) : To a stirred solution of 2-amino-4,6-disubstituted pyrimidine 3 (5 mmol) and a catalytic amount of tetrabutyl ammonium bromide (TBAB, 0.10 g) in dry acetonitrile (10 mL) was added dropwise a mixture of 3-(2,4-dichlorophenyl)-5-methylisoxazole-4-formyl isothiocyanate 2 (1.56 g, 5 mmol) in dry acetonitrile (10 mL) at room temperature within 0.5 hr. The mixture was then refluxed with stirring for 2 hr.…”

Thiourea and Selenourea and Their Applications

“…Reactions of (benzotriazol-1-yl)carboximidamides and acyl-or arylaminocarbonyl-(benzotriazol-1-yl)carboximidamides with hydrogen sulfide give the corresponding thioureas and N-acylthioureas or N-carbamoylthioureas, respectively (Scheme 11) [29]. product has been achieved by the changing the concentration of KSCN as shown in Scheme 14 [32].…”