Type B Syntheses

Type B Syntheses (C—C—N + C—S).—Thiocyanation of oi -unsaturated jS-amino-ketones R3HNCRi=CHC(0)R2 (Ri = Me or Ph R= = Me, Ph, or OEt R = H, Me, or Ph) with cyanogen occurs at the olefinic H-atom, or gives a 2-imino-A -thiazoline, or its rearranged isomer (8), depending upon the structure of the starting material and reaction temperature. The thiocyanated alkenes are cyclized to mixtures of the cyclized products in acid or alkali, or else thermally. 

Type B (C—C—+ C—S) Syntheses.—Primary and secondary enamines and chlorocarbonyl sulphenyl chloride undergo a cycloacylation to thiazolones. Ethyl 3-aminoacrylate (7 X = OR ), for example, produces the 2-oxothiazole-5-carboxylic acid esters (8 X = COR ) in 60—80% yields. /3-Aminocrotonic nitriles (9) similarly afford the corresponding 5-cyano-heterocycles.  

The synthesis of the thiazole nucleus from aminothiocyanogen and ketones (these Reports, Vol. 2, p. 589) is also applicable to enamines derived from jS-dicarbonyl compounds. Thus, 3 aminocrotonic ester (10) or 2-aminopent-2-en-4-one (11) yield the intermediate enamines (12), which are cyclized to 2-aminothiazoles (13) under the influence of alkalis, and to A -thiazol-2-ones (14) by acids.  

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The principal difficulty associated with this type of synthesis is in the availability of a-aminoacyl compounds, e.g. a-aminoaldehydes, a-aminoketones, etc., and most type B syntheses rely on the generation of these compounds in situ, where the self-condensation occurs spontaneously. A large number of research groups have addressed themselves to this problem and a variety of routes are now available. 

No practical type B syntheses of quinoxalines are commonly in use, largely because of the fact that type A syntheses are more facile however, some phenazine syntheses of this type are known, particularly those described in the older chemical literature. Hillemann (38CB42) has effected dimerization of 0-bromoaniline by heating its solution in nitrobenzene with K2CO3 and copper powder. The reaction is believed to proceed through the intermediacy of 5,10-dihydrophenazine, but the latter has not been isolated (Scheme 68). 

Type B syntheses are characterized by the reaction of an amidoxime 77 with carbon disulfide to afford 5-mercapto-1,2,4-thiadiazoles 78. The corresponding 5-amino derivatives 80 are obtained from the reaction of iV-sulfenylami-dines 79 with arylisothiocyanates (Scheme 8) <1996CHEC-II(4)307>. 

Type B syntheses starting from HPs require a Dimroth rearrangement. By contrast, in the following reaction paths, the 1,3 orientation of two nitrogen atoms needed to form the triazole ring of the TP is preformed in the pyrimidine precursor. 

Type B Syntheses of Thiazoles (C-C-N + C-S). Enamino-esters CF3C-(NH2)=CHC02Et, with ClCOSCl, are converted into 2-chloro-4-trifluoro-methylthiazole-5-carboxylic esters and derivatives. Thioketens and 3-dimethylamino-2J -azirines give 2-substituted 4-(7V7V-dimethylcarbamoyl)-5-(MV-dimethylamino)thiazoles. ... 

Type B Syntheses of df-Thiazolines (C-C—N + C-S). CF3C(NH2)=CHC02Et was heated with ClCOSCl in benzene to yield the A -thiazolin-2-one (158). Compound (158) and POCI3 in DMF were refluxed to give the thiazole (159). We also find the cyclo-condensation of MeC(NH2)=CHCN with ClCOSCl, giving 5-cyano-4-methy 1--thiazolin-2-one... 

Synthesis. - Type B Syntheses (C-C—N + C-S). 2-Arylaminothiazolidines are prepared from R2NHCH2CH2CI and R NCS (EtgN, CHCla). ... 

Type B Syntheses of Benzothiazoles (CfJBs-N-C-S). Following a known method, arylthioureas were oxidized to give substituted 2-aminobenzo-thiazoles and 2-[(2-thioxoimidazolidin)-3-yl] benzothiazole by bromine, and substituted 2-aminobenzothiazoles by SOCl2 or Br2 (CI2) and... 

The formation of the diketopiperazine ring from proline-containing peptides can occur in two ways (see type A and type B). Entropy considerations predict that type A syntheses should result in relatively easier cyclization than type B syntheses. In both approaches, the presence of a proline residue in the peptide allows ready cyclization to the diketopiperazine under conditions which would leave other nonproline-containing dipeptides unaffected. ... 

Type B Syntheses C—C—N + C—S). Attempts to synthesize 1,3-thiazine derivatives by the condensation of alkylamines, carbon disulphide, and dialkyl maleates gave instead the 2-thioxothiazolidin-4-ones (rhodanines) (77). ... 

Other Type B Syntheses.— The interaction of 2-picoline with 3-substituted anilines in the presence of sulphur under Willgerodt-Kindler conditions, reported... 

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