Thiazolines from thioamides

Similarly, 5-thiazole alkanoic acids and their salts are obtained from thioamides and /3-halo -y-keto acids (695). Thus thioarylamides condensed with 3-aroyl-3-bromopropionic acid (88) in isopropanolic solution in the presence of Na COs give first 4-hydroxy-2-aryl-A-2-thiazoline-5-acetic acid intermediates (89), which were dehydrated in toluene with catalytic amounts of p-toluene sulfonic acid to 2,4-diaryl-5-thiazole acetic acid (90) (Scheme 39) (657), with R = H or Me Ar = Ph, o-, m- or p-tolyl, o-, m-, or P-CIC6H4, 0-, m-, or p-MeOC(iH4, P-CF3C6H4, a-thienyl, a-naphthyl (657). 

E. Pfund, S. Masson, M. Vazeux, T. Lequeux, Syntheses of ot-fluoro-ot,j -unsaturated thioamides and thiazolines from a fluorophosphonodithioacetate, J. Org. Chem. 69 (2004) 4670 676. 

From Thioamides and Acetylenedicarboxylic Acid. The interaction of o-aminobenzenethioamides and dimethyl acetylenedicarboxylate does not yield the quinazoline-4(l )-thione (164) as might be expected from the behaviour of the corresponding o-aminobenzamides, but produces 2-(o-aminophenyl)-5-methoxycarbonylmethylidene-2-thiazolin-4-one (165) in high yield. ... 

Further Syntheses from Thioamides (Linear and Cyclic). The acid-catalysed cyclization of A -allylthioureas provides a synthetic route to 2-thiazolines. The reaction, performed in 60—90% sulphuric acid, is initiated by protonation, producing the highly resonance-stabilized thiazolinium cations (168), and is completed by hydrolysis to (169). It is an example of... 

Synthesis from Thioamides and Related Compounds. Type B, CgHs—N-—C—S.) The action of a large excess of thionyl chloride on substituted thioureas of type (22) (incorporating a jS-hydroxy-group in their Aralkyl group) produces 2-aminobenzothiazole derivatives (23) preferentially, rather than thiazolines (24) or oxazolines. Thionyl chloride, like sulphuryl... 

Fluorinated dithioester 39 has also been involved in thioacylation reaction of enantiopure aminoalcohols leading to the corresponding hydroxylated thioamides. The later, treated either by SOCVpyridine, CH3SO2CI, or PhjP/DEAD, cyclise into thiazolines 42 without epimerisation and in excellent yields. An interesting application of this reaction is the synthesis of a new type of modified nucleotides such as 43 and 44 by a one pot reaction simply by mixing the dihydroxy substituted thioamide (obtained from 39 and the 2-amino-l,3-... 

One of the most valuable methods for the preparation of A2-thiazolines is of this class. The reaction of 2-haloalkylamines (334) with thioamides, metal thiocyanates or carbon disulfide give 2-alkyl- or -aryl- (335), 2-amino- (336), and 2-mercapto- (337) A2-thiazolines, respectively (Scheme 218) (17CB804). A method derived from the last procedure leads to a convenient synthesis of 2-phenyl-A2-thiazolines (340) under very mild conditions and consists of the condensation between a-aminothiols (338) and thiobenzoylmercaptoacetic acid (339 Scheme 219) (74TL1863) (this method could be better classified under Type E, Section 4.19.3.2.5). 

The synthesis of enantiopure thiazolines has been reported. The mixture of enantiomerically pure diastereoisomeric amido selenides 64, obtained from the reaction of camphorselenyl sulfate with trans alkenes, when treated with Lawesson s reagent affords a mixture of two thioamide derivatives 65a and 65b. The two diastereoisomeric thioamide selenides were easily separated by chromatography, each was then treated with phenyl selenyl chloride which caused deselenylation to occur in a stereospecific manner furnishing the thiazolines 66a and 66b in an enantiopure form <02TA429>. 

Thiazolines 186 and 187 were prepared from acetic and benzoic thioamides and bis-trifluoromethyl enone 188. Benzoic thioamide underwent oxidation readily upon treatment with />-toluenesulfonic acid (PTSA) to form the corresponding thiazole 189, whereas methyl variant did not (Scheme 72) <2003JST(646)1>. 

Benzimidoyl chlorides and )V, -dimethyl-)V -thiobenzoylfoimamidine react to afford thioimidic acid anhydrides (270 Scheme 40). Spirocyclic thioimino esters have been prepared from benzimidoyl chlorides and thiazolin-S-thiones.- Carboxylic acid imidothio acid anhydrides (271) can be synthesized from carboxylic acid chlorides and secondary thioamides. ... 

Thioxo-2-thiazolines (334) can be synthesized by treatment of A(,iV-disubstituted thioamides (332) with dithiaphosphetane (333), an easily available sulfurating agent similar to the Lawesson s reagent. In turn, compounds (332) can be prepared from azirines and thiocarboxylic acids (Scheme 84) <87HCA1001>. 

As described previously, thiazolines are versatile intermediates to thiazoles. In addition, thiazoline rings are structural motifs found in numerous natural products. Among a variety of methods for the construction of thiazolines, the cyclodehydration protocol is perhaps most popular. Bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) is used as the cyclo-dehydrating agent for the conversion of 3-hydroxy thioamide 60 to the bis(thiazoline) 15 <04H(63)773>. A more recent protocol for the cyclodehydration of P-hydroxy thioamides to thiazolines involves pyridine-buffered phosphorus oxychloride as exemplified by the formation of 62 from 61 <04JA12897>. 

Several thioamides have been prepared by treating nitriles with hydrogen sulfide. " A few -thiazoline derivatives (XI-1S6) have been isolated from the reaction of pyridylacetonitriles with 2-aminoethyl thiol. 3-Pyridylacetoni-... 

Thiazolines can be obtained through cyclodehydration of the compounds bearing C(=S)-NH-C-C-OH moiety (P-hydroxy thioamide). Exposure of P-hydroxy thioamide 33 with DAST brings about intramolecular cyclization to provide thiazoline 34 and its epimer in 75% yield.The epimer results from racemization of the proline-derived residue due to strong acid conditions of DAST (13TL3150). Compound 34 represents the (i -dehydrobutyrine-thiazoline-proline-leucine fragment ofvioprolides B and D isolated from Cystobacter violaceus. 

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