Synthesis of 4-amino-5-arylmethyl-2-bromothiazoles

Abstract

Thiazole derivatives with 4-amino substituents are comparatively inaccessible [1]. We have developed a simple method for the synthesis of such compounds based on products from the thiocyanoarylation of acrylonitrile (Ia,b). cx-Thiocyanatonitriles add hydrogen bromide to cyclize readily to thiazole derivatives (IIa,b):

Discovery and Potency Optimization of 2‐Amino‐5‐arylmethyl‐1,3‐thiazole Derivatives as Potential Therapeutic Agents for Prostate Cancer

“…These, after reaction workup and isolation of the crude material, were reacted, without further purification, with thiourea in refluxing ethanol to provide the requisite 2-amino-5-benzyl-1,3-thiazole core building blocks 4 in moderate to good yields. Thus, we introduced two notable improvements to the original procedure [8,9], namely, the use of the biphasic toluene-water reaction medium throughout the syntheses, and avoidance of the purification of intermediates 7 by distillation. These, however, lead to virtually no yield improvement compared to the originally described procedure but rather simplified the syntheses operationally.…”

“…According to the literature analogy [8,9], the 2-amino-5-benzyl-1,3-thiazole precursors 4 substituted at the benzyl portion, can be synthesized in two steps from readily available anilines 5 as shown in Scheme 1. The respective diazonium salts 6 were reacted with acrolein in the pres- ence of cupric chloride in biphasic toluene-water medium to provide respective 3-aryl-2-chloropropanals 7.…”

The synthesis and anticancer properties of 2-(4-amino-5-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-N-(5-R-benzylthiazol-2-yl)-acetamides

“…At the first stage acrolein was chloroarylated by diazonium salts in the presence of copper(II) chloride under Meerwein arylation conditions. Refluxing of 3-aryl-2-chloropropanals 2a-h and thiourea in ethanol gave 5-substituted 2-aminothiazoles 3a-h [15,16],…”

“…Combine the extract with the organic phase, dry over MgSO 4 , evaporate, and distill the residue under reduced pressure. Compounds 2a, c-g were described earlier [15,16]. Heat the mixture of 0.8 g of thiourea and 0.01 Mol of aldehyde 2 in 10 ml of ethanol for 1.5-2 h under reflux.…”

“…Filter the precipitate and recrystallize from CCl 4 or C 6 H 6 -CCl 4 . Compounds 3a, c-g were described earlier [15,16]. The general procedure for the synthesis of N-(5- (R-benzyl)-1,3-thiazol-2-yl)-2-chloroacetamides (4a-h).…”