L-acetyl-2-thiourea

From the diverse examples on Hantzsch syntheses reported, the reaction of 2-bromo-4 -methylacetophenone and l-acetyl-2-thiourea was exemplarily chosen to be represented here [10]. 

GlaxoSmithKline Pharmaceuticals in Harlow, UK, performed the Hantzsch synthesis of 2-bromo-4 -methylacetophenone and l-acetyl-2-thiourea in NMP (N-methyl-2-pyrrolidone) using a microchip reador under EOF conditions [10] (for EOF see [11]) [10] This is claimed to be the first example of a heated organic reaction performed on a glass chip reactor under electroosmotic flow control, whereas only room temperature reactions were made earlier. In a wider scope, the Hantzsch synthesis is a further example to evaluate the potential of microfluidic systems for high-throughput... 

Bromooctane refluxed 24 hrs. with 1.1 equivalents l-acetyl-2-thiourea in ethanol -> n-octyl mercaptan. Y 53%. - This method obviates the need for a separate hydrolysis step and may prove useful for the prepn. of water- and alkali-sensitive thiols. F. e. s. D. L. Klayman, R. J. Shine and J. D. Bower, J. Org. Chem. 57, 1532 (1972). 

In this sequence, substitution by 1 mol of dimethylamine first replaces the benzylmercaptan leading to 5-acetyl-2-dimethylamino-6//-l,3-thiazine (197). The thiazine then undergoes attack by dimethylamine excess at C-6, leading to the thiourea (198). The benzylmercaptan liberated in the first reaction may act as a nucleophile (BzS",H2NMe2+), and a different thiourea substituted by dimethylamino and benzylthio groups is obtained. The action of pyrrolidine on 1,3-thiazine-4-ones (194) can be seen as a Michael addition followed by elimination of H2S. In acidic media, the linear compound obtained is cyclized to the pyrimidone (200) (Scheme 80)... 

Thiourea derivatives (11) are available from 2-amino-2-deoxy-l,3,4,6-tetra-Q-acetyl-a-D-glucopyranose (9) or from the corresponding 2-isothiocyanate (10) by treatment with methyl isothiotyanate or a primary amine, respectively (Scheme 4). On exposure to hydrobromic acid they cyclise to give glucopyrano[2,l-d]-2-thiazolinium bromides (12). ... 

N-Acetylation. A soln. of cupric acetate monohydrate in ethanol added to a soln. of l-(3-phenoxypropyl)-3-phen-yl-2-thiourea in the same solvent, and refluxed 7 hrs. l-(3-phenoxypro-pyl)-3-phenyl-3-acetylurea. Y 83%. 

Furium. N[4-(5-Nitro-2-furanyl)-2-thia2olyl]acetamide, has demonstrated activity against baciUi and pathogenic enterobacteria (24). The product, prepared from thiourea and 2-bromo-l-(5-nitro-2-furanyl)ethanone followed by acetylation of the intermediate aminothia2ole with acetic anhydride in pyridine (25), is marketed in several countries for both human and veterinary use. 

An acylated glycosyl halide, such as a 2,3,4,6-tetra-O-acetyl derivative, is treated with thiourea. The resulting pseudothiouronium salt is hydrolyzed with aqueous potassium carbonate to give the 2,3,4,6-tetra-0-acetyl-l-thio-(3-D-glucopyranose,48 which then is alkylated. 

Type D synthesis, where the 3,4-CN bond is being formed, involves the reaction of thiosemicarbazones of aldehydes, ketones, and esters 97 with 3,3-pentamethyleneoxaziridine 98 to afford 5-imino-3,3-pentamethylene-l,2,4-thiadi-azolidines 99 (Equation 27). yV-Acylthioureas also undergo this transformation but, whereas this reaction is fairly general for thiosemicarbazones, only acetyl and benzoyl thioureas give 1,2,4-thiadiazolidines <1996CHEC-II(4)307>. There have been no new reports of type D syntheses since the publication of CHEC-II(1996). 

Glycosyl halides (7a-e) were stereoselectively transformed into l,2-tra s-thio-glycoses by i) (8a-d, 8j) a two-step procedure via the pseudothiourea derivatives [9,10a] the substitution of halide by thiourea is mostly a S l-type reaction since acetylated 1-thio-a-D-mannose (8b) was obtained from acetobromoman-nose (7b) [9cj ii) (8e-i) using thiolates in protic and aprotic solvents [10], or under phase transfer catalysis conditions [11]. Another approach involved the reaction of thioacetic acid with 1,2-trans-per-O-acetylated glycoses catalyzed with zirconium chloride [12]. The 1,2-trans-peracetylated 1-thioglycoses (8e-h) were obtained in high yield. No anomerized products could be detected in these reactions (Fig. 1). 

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