2-Thiazolyl acetals

Copper-catalyzed cross-dehydrogenative coupling (CDC) reactions of (benzo)thiazoles 49 with cycHc ethers 50 have been developed under mild conditions (130L4600). Notably, the 2-thiazolyl acetals, known as the masked 2-thiazolecarboxaldehydes, could be successfully obtained by this CDC reaction. 

For example, (2-phenyl-4-thiazolyl) acetate (87), R = H, was obtained in good yield from thiobenzamide and ethyl-7-bromo acetoacetate (86) as in Scheme 38 (640). 

Phenyl-5-thiazolyl)acetic acids variously substituted in the 2-position give the corresponding naphtho[l,2]thiazoles in the presence of acetic anhydride and sodium acetate (397, 426, 857). 

C17H12CINO2S, (2-Phenyl-4-(p-chlorophenyl)-5-thiazolyl)acetic acid, 44B, 366... 

The Curtius rearrangement in acetic anhydride of the azide (8) prepared from 4-carboxythiazole yields 4-acetamidothiazole (Scheme 8) (47). The same reaction starting with ethyl-2-methyl-4-thiazolyl carboxy-late, failed to give the 4-aminothiazole (48). Heterocyclizations are more convenient synthetic methods (Chapter II. Table 40). 

The preparation and spectroscopic properties (infrared, ultraviolet, NMR) of iV-alkoxycarbonyl-N -(2-thiazolyl)thioureas (268) have been studied by the Nagano group (78, 264). These compounds react with bromine in acetic acid or chloroform to give 2--alkoxycarbonylimino-thiazolo[3,2-h]thiadiazolines (Scheme 162), whose structures were established by mass spectroscopy, infrared, NMR, and reactivity patterns (481). 

The thiazolyl-2-thioglycollic acid (119) undergoes intramolecular ring closure to give mesoionic compound 120 under treatment with acetic anhydride and triethylamine (Scheme 60) (192). The parent acid (119) can be recovered from 120 by hydration with hot 50% aqueous sulfuric add. Compound 120 affords monohydrate of bis(-cyclopentenothiazolyi-2-thio)acetone (121) (192). 

By refluxing 54 and thioformamide for 16 hr m aqueous acetone solution, the expected compound 55 was obtained (Scheme 25). 55 in acetic medium, after treatment with hydrochloric add and zinc, gives 2-(4-thiazolyl)benziinida2ole derivatives 56 (554, 593). 

Oxidation of carbon side-chains has resulted in the synthesis of dithiazolyl ketone (82) and thiazolyl phenyl ketone (83). The hydrocarbon chain can also be dehydrogenated in acetic acid in the presence of... 

Thiazolyl magnesium halide reacts at low temperature with acetic anhydride to give acetylthiazole in low yield (10 to 20%) (31). 

The Claisen condensation of an aliphatic ester and a thiazolic ester gives after acidic hydrolysis a thiazolylketone (56). For example, the Claisen condensation of ethyl 4-methyl-5-thiazolecarboxylate with ethyl acetate followed by acid hydrolysis gives methyl 4-methyl-5-thiazolyl ketone in 16% yield. 

CN [25-[2a,3a(Z)]]-[[[2-[[2-[[(aminocarbonyl)oxy]methyl]-4-oxo-l-sulfo-3-azetidinyl]amino]-l-(2-amino-4-thiazolyl)-2-oxoethylidene]amino]oxy]acetic acid... 

Yadav and Kapoor <2003TL8951> reported on a microwave-assisted ring closure leading to novel thiazolo[l,3,5]-triazines, as shown in Scheme 36. This three-component one-pot procedure started from the thiazolyl Schiff base 230, to which ammonium acetate and an aldehyde was added. In the first step, the azomethine moiety of the Schiff base reacted with ammonia to give the zwitterionic first intermediate 231, which underwent deprotonation to the amine 232, and, finally, reaction of this second intermediate with the aldehyde involving the ring-closure step afforded the product 233. It is important to emphasize that the MW-assisted technique ensured high yields (76-88%)... 

Anodic regioselective fluorination of a-phenylsulphenylated ethyl acetates, 1-naphthalene and 2-pyridine derivatives [80], l-aryl-3-(phenylthio)oxindoles and 2-substituted-3-oxo-4-(phenylthio)-l, 2, 3,4-tetrahydroisoquinolines [81], 2-benzo-thiazolyl and 5-chloro-2-benzothiazolyl sulfides [82], a-(phenylsulfenyl)lactams [83], as well as various heterocycles such as thiolanones, oxathiolanones, dithi-olanones, 3Fl-l,4-benzoxathian-2-ones [84] in Et3N-3HF or Etr NF- HF [n = 3,4), has been reported. 

A study of reactions of NBS in acetic acid and acetic anhydride with thiophenes substituted in the a-position by groups such as 4-thiazolyl or 2-quinolinyl demonstrated that after initial perbromide formation (at around 20°C), slow conversion into C-brominated products followed. Reactions carried out above 40°C with one molar equivalent of NBS gave 5-bromo products only, but introduction of electron-donating groups into the thia-zole substituent and excess brominating agent led to some thiazole bromi-nation. With a 2-aminothiazolyl substituent, bromination took place exclu-... 

The remarkable stability of the thiazole ring allowed synthetic manipulations of the thiazolyl ketol acetates, which extended considerably the scope of the above C-formylation method of furanoses and pyranoses. Instead of the reductive removal of the acetoxy group, the /V-glycosidation of either a- or p-anomer 73 with TMSN3 afforded stereoselectively the azido galactopyranoside 75 in 88% isolated yield (Scheme 22) [77]. The cleavage of the... 

The same type of reaction sequence was employed for the conversion of the thiazolyl ketol acetate 79 into the azido aldehyde 80 (Scheme 23) [77], a key precursor of the natural product hydantocidin 81 [78]. 

Famotidine, Also known as Pepcid, famotidine [76824-35-6] (AT-(aminosulfonyl)-3-([[2-[(diaminomethylene) amino]-4-thiazolyl] methyl]thio)propanimidamide (2) is a white to pale yellow crystalline compound, freely soluble in glacial acetic acid, slighdy soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol. It may be prepared by the method described in Reference 3. 

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