5/7-Thiazolo pyridine-5 -ones

Anhydro-3-hydroxy-2-phenylthiazolo[2,3-6]thiazolylium hydroxide (407) underwent ready thermal reaction with alkynic and alkenic dipolarophiles in refluxing toluene. With the former dipolarophile sulfur was lost from the intermediate 1 1 cycloadduct (408) to give the substituted 5H-thiazolo[3,2- i]pyridin-5-ones (409). With the latter, the intermediate (410) lost H2S, also forming (409). 

The reaction of 6-amino[l,2,4]triazin-5(2//)-ones or its thione derivatives 680 with acetic anhydride gave the 6-acetamido derivatives 681 and 682, respectively. Treatment with phosphorus pentasulfide in pyridine gave thiazolo[5,4-e][l,2,4]triazines 683 (84LA283 87AJC491) (Scheme 142). 

A novel series of 5//-thiazolo[3,2-a]pyridine-5-ones 64 is prepared by addition of malonic esters 59 to 2-alkynylthiazoles 60 <06H(67)523>. A plausible reaction mechanism involves an intramolecular cyclization of the initial adduct 61 to give the cyclobutenoxide intermediate 62. Ring-opening of this intermediate and subsequent cyclization lead to 5//-thiazolo[3,2-a]pyridine-5-one 64. 

The Liebeskind group cross-coupled 4-chloro-2-cyclobutenone 69 with 2-tribuylstannyl-benzothiazole to synthesize a-pyridone-based azaheteroaromatics [48], The adduct 70 underwent a thermal rearrangement to afford a transient vinylketene 71, which then intramolecularly cyclized onto the C—N double bond of benzothiazole, giving rise to thiazolo[3,2-a]pyridin-5-one 72. In another case, 2-acetyl-4-trimethylstannylthizaole (73) was coupled with an acid chloride 74 to form the desired ketone 75 [49]. 

Arylidene-33-diethyl-3,4,6,7-tetrahydro-2//-thiazolo[3,2-/j][l, 4 ]-tetrazin-6-ones 53 have been synthesized in a single step by the condensation of tetrahydro-l, 4 -tetrazin-3-thione 52 with ethyl chloioacetate and aldehydes in the presence of pyridine and piperidine. Condensation of 53 with hydrazine afforded fused derivatives 54 <98IJC(B)819>. 

Epicorazine A (8S,9R,9aS,10aS)-9-Ethenyl-8-(P-D-glucopyranosyloxy)- 2,3,9,9a,10,10a-hexahydro-5H,8H-pyrano[4,3-d]thiazolo- [3,2-a]pyridine-5-one Xylostosidine... 

Treatment of 3,6-dihydroxy-3,4-dihydro-2//-pyrido[2,l-h][l,3] thiazinium salt (86) with orthophosphoric acid at 140°C for 34 h or with cone, sulfuric acid at ambient temperature for 5 h afforded 1 1 and 3 1 mixtures of pyrido[2,l-6][l,3]thiazine (87) and thiazolo[3,2-a]pyridine (88), respectively (70ACS2949). Under basic conditions, only extensive destruction of 86 was observed. When 3-hydroxy-2,3,4,6-tetrahydro[l,3]thiazino[2,3-a]isoquinolin-6-one was left to stand in cone, sulfuric acid at room temperature overnight, 4,6-dihydro[l,3]thiazino[2,3-a]isoquinolin-6-one was obtained in 61% yield (72ACS1620). 9-Oxido-3,4-dihydro-2H-pyrido[2,l-h] [l,3]thiazinium betaine did not undergo cycloaddition even under extreme conditions [81JCR(S)208],... 

Thiazolidines are also known to selectively intercept the biochemical processes of the pathogenic organisms such as bacteria, virus, and fungi, in the host species. Thiazolidines introduction into the HIV/AIDS (Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome) therapy is due to l-aryl-lff,3ff-thiazolo[3,4-a]benzimidazole (TBZ) analogues (Fig. 26). Barreca et al. have modified the TBZ by opening its B ring to explore the thiazolidines namely 2-(2,6-dihalo phenyl)-3-(substituted pyridin-2-yl)-thiazolidin-4-ones (Table 16) as potential anti-HIV-1 RT agents [173]. 

Japanese workers were the first to use the reactive properties of nitrile compounds to synthesize thiazolo[3,2-a]pyridin-3(2//)-ones (77S839). Ethyl a-cyanocinnamate (88, R = Ph, R = CO Et) reacts with ethyl mer-captoacetate in the presence of triethylamine to give 5-amino-2-benzyli-dene-6,8-bis (ethoxycarbonyl )-7-phenyl-7//-thiazolo [3,2-n]pyridin-3(2//)-one (89, R = R- = Ph, R = R = C02Et), which is also obtained from the reaction of 5-benzylidene-2-ethoxycarbonylmethyl-2-thiazolin-4-one (90a) with ehtyl a-cyanocinnamate (77S839). Reaction of 90a,b with ben-zylidenemalononitrile (88, R- = Ph, R" = CN) and of 90c with ethyl a-cyanocinnamate furnish the respective bicyclic compounds 89 [83ZN(B)781] (Scheme 21). Similar results were also obtained from 88 (R = furan-2-yl-or thiophen-2-yl) (86M105). 

Synthesis of thiazolo[3,2-a]pyridin-3(2//)-one can also be accomplished by an alternate route in which a thiazole ring is built onto a pyridine ring. Thus, copper-catalyzed reaction of piperidine-2-thione (95) with methyl diazoacetate affords 5,6-dihydro-7//-thiazolo[3,2-a]pyridin-3(2//)-one 97) (80LAI68) (Scheme 22). During the reaction uncyclized intermediate (96) could not be isolated, it evidently cyclized immediately to the bicyclic product (97), whereas with the pyrrolidine-2-thione the corresponding uncyclized product was isolated (80LAI68) (Scheme 22). 

Diazacyclotridecane-2-thione (231) reacts with chloroacetic acid or ethyl chloroacetate to furnish thiazolo [3,2-a]-[l,3]diazocyclotridecane-3(2//)-one (232). Compound 231, on condensation with ethyl chloroacetate and aldehydes in the presence of pyridine and piperidine, yields arylidene-thiazolidinone (233) which is also obtained from 232 and aldehydes (83J1C970) (Scheme 56). No spectral data are recorded. 

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