Thiazolo thiadiazines

Because of its importance in biological areas, special efforts have been made with the synthesis of the thiazolo[2,3-t]-[l,2,4]thiadiazole derivative 308 <2001BML1805>. The pathway started from the benzothiazole derivative 305 which was treated with chlorosulfonylacetyl chloride to form an intermediate 306, which underwent cyclization to a second intermediate 307 with hydrogen chloride elimination. The last step is the attack of the first intermediate 306 at the thiadiazine carbon atom to form the final product 308. 

Some rearrangements in the 1,3,4-oxadiazole series are explained by an /pso-nucleophilic attack by the side-chain (Scheme 72). Thus, under amination conditions, oxadiazolyl ketones 458 give the rearranged thia-zoles 460 via the enamino compounds 459 as intermediates. Sometimes, performing the reaction in refluxing acetic acid causes direct cyclodehydration into thiazolo[2,3-c]-s-triazoles. In a similar way, hydrazine in refluxing acetic acid converts compounds 458 into triazolo(3,4-b)thiadiazines 463... 

The amidine 61 when treated with alkylsulfonyl chlorides forms the intermediate thiazoline diazadiene 62 which cyclises to give the thiazolo[3,2-6]-l,2,4-thiadiazine-l,1-dioxide 63 in moderate yield. This is the first synthesis of this class of compound <02TL4099>... 

Disubstituted 2-thioxo-pyrido[2,3-d]pyrimidinones condensed with aldehydes in the presence of chloroacetic acid to yield thiazolo[2,3-a]pyrido[2,3-. One-pot alkoxylation at the 7-position of 6-arylpyrazino[2,3-c][l,2,6]thiadiazine 2,2-dioxides with NBS or NCS in the appropriate alcohol has been studied <02EJ02109>. 

The practical utility of the facile addition of mercaptoacetic acid across the double bond of an azomethine has been used in the synthesis of thiazolo-triazolothiadiazin-6(7//)-one (328). Thus, 7//-3-methyl-5-triazolo[3,4-f>]thiadiazine hydrochloride (327), obtained by reacting l-amino-2-methyl-j-triazolyl-2-thione (326) with chloroacetaldehyde di-ethylacetal, reacts with mercaptoacetic acid in the presence of p-toluenesulfonic acid in boiling anhydrous benzene for 40 hr using a Dean-Stark water separator followed by basification with sodium bicarbonate to furnish 8a//,9//-3-methylthiazolo[3,2-u]-[l,3,4]triazolo(3,4-f>](1,3,4]-thiadiazin-6(7//)-one (328) (74IJC287) (Scheme 77). The absorption at 1725 cm (lactam carbonyl) in product 328 supports the cyclic structure in preference to the open-chain acid structure. 

The electrochemical oxidation of catechols in the presence of 6-methyl-l,2,4-triazin-3-thion-5-one and 4-amino-6-methyl-l,2,4-triazin-3-thion-5-one as nucleophiles in aqueous solutions provided an efficient electrosynthesis of thiazolo[3,2-fi][l,2,4]triazin-7-one and l,2,4-triazino[3,4- ]l,3,4-thiadiazine derivatives respectively <06TL1713> <06TL8553>. 

Substituted 2 f-l,2,4-benzothiadiazin-3(4//)-one 1,1-dioxides are available by a one-pot intramolecular Friedel-Crafts reaction involving the action of chlorosulfonyl isocyanate on a secondary aromatic amine in the presence of aluminum chloride <85IJC(B)1295>. Chlorosulfonyl isocyanate is also employed in the synthesis of oxazolo- and thiazolo[2,3-z(][l,2,4]-thiadiazin-3(2//)-ones (196 X = O and S) from 2-ethyloxazolines (195 X = O) and 2-ethylthiazolines (195 X = S) respectively (Scheme 33) <93SC121>. 

The totally saturated compound (75) represents the first example of the thiazolo[2,3-c] [l,2,4]thiadiazine ring system (6). This compound was obtained as a ring enlargement product in the reaction of (74) with ammonia (Equation (13)) (89CL89>. Reaction of 2-ethyloxazoline (76 X = O) or 2-ethylthiazoline (76 X = S) with chlorosulfonyl isocyanate followed by treatment with triethylamine led to the ring closed products (77 X = O or S), derivatives of ring systems (7) and (8), respectively (Equation (14)) <93SC121>. 

Aryl-2-(carboxymethyl)(or carboxyethyl)thiazolo[3, 4 2,3]-l,2,4-triazolo[5,4-3]-l,3,3-thiadiazines 234 are obtained from 2-aryl-3-thioureido-4-thiazolidinones 235, which are formed by the addition-condensation of aldehyde thiosemi-carbazones 237 and mercaptoacetic acid. Compounds 235 undergo chemoselective intramolecular heterocyclizations to 5-aryl-2-mercapto-l,5-dihydrothiazolo[3,4- ]-l,2,4-triazoles 236, which in turn undergo condensation with a-amino acids to yield 1,3,5-thiadiazines 234 (Scheme 44) <1994JFA811>. 

Spiro [2H-l-benzopyran-2,2 -benzothiazolines] spiro [pyrroli din-3,1 -(py rro-lidino-[3,4-c]pyrrolidones)] sydnones thiadiazines thiadi azoles thiaoxaborepanes thiazaphospholanes thiazolo[3,2-a]benzimidazoles thiazolo[3,4-a]benzimidazoles thiazolo[3,2-a][l,3]diazepines thiazolo[2,3-b]quinazolines thieno[2,3-e][l,4]diazepines thieno[2,3-d]pyrimidines... 

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