Benzimidazole thiadiazoles

The synthesis of the benzoimidazo[l,2- ][l,2,3]thiadiazole 61 can be explained using the same mechanistic model to that used for the Hurd-Mori reaction. The amino benzimidazole 58 when treated with thionyl chloride at reflux affords the benzoimidazo[l,2-r ][l,2,3]thiadiazole 61. If, however, the reactant 58 is treated with thionyl chloride at room temperature, the chloromethyl derivative 59 is formed. This derivative was then transformed into product 61 on reflux with thionyl chloride. The proposed mechanism for the formation of product 61 is for the initial formation of the sulfoxide 60, which then undergoes a Pummerer-like rearrangement, followed by loss of SO2 and HC1 to give the c-fused 1,2,3-thiadiazole 61 (Scheme 7) <2003TL6635>. 

Thermolysis of the thiadiazole (164) leads to elimination of isocyanate and sulfur giving the triazine derivative (167). If the thermolysis is carried out in the presence of phenols 2-aryl-benzimidazoles (168) are produced <85JCS(P1)1007>. The S—N bond of (157) is readily cleaved with both N- and C-nucleophiles. Thus, treatment of (157) with an excess of amine gives the sulfenamide (169) (Scheme 39) and reaction of (157) with active methylene compounds leads to derivatives of type (170) (Scheme 39) which on heating furnish (171). Cyanide ion inserts into the S—N bond of (164), probably via the intermediate (172) which immediately recyclizes to give the thiadiazinone (173) (Scheme 40) <85JCS(P1)1007>. 

Other desulfurization reagents are also effective, and the dithiadiazine (149) gives the thiadiazole (150) on treatment with triphenylphosphine (76JCS(P1)38). Triphenylphosphine also converts thiadiazines (144) into pyrazoles (77S485), and 2,1,4-benzothiadiazines (151) into the corresponding benzimidazoles (74BRP1350277). This latter reaction is in marked contrast to that of the isomeric 1,2,4-benzothiadiazines (145), which lose NH rather than S on treatment with triphenylphosphine. 

Herbicides that act as inhibitory uncouplers are dinitro-phenols, N-phenylcarbamates, acylanilides, halogenated benzoni-triles, substituted imidazoles, substituted benzimidazoles, bromofenoxim, substituted 2,6-dinitroanilines, pyridinols, and substituted 1,2,4-thiadiazoles (2). 

A large body of information on the methods of synthesis, application, structure, and properties of all known five-membered nitroazoles - pyrazoles, imidazoles, triazoles, tetrazoles, oxazoles, isoxazoles, oxadiazoles, thiazoles, isothiazoles, thiadiazoles, selenazoles, selenadiazoles, and their benzo analogs - indazoles, benzimidazoles, benzoxazoles, benzisoxazoles, benzoxadiazoles, benzothiazoles, benzoisothiazoles, benzothiadiazoles, benzotriazoles, benzoselenazoles, and ben-zoselenadiazoles has been systematized, summarized, and critically discussed in this monograph. 

Several benzimidazole-4,7-diones were synthesized and tested for antitumor activity (88JMC260). There is also a report on oxidation of 4-amino-or 4-aikoxybenzo-2,l,3-thiadiazoles with hydrogen peroxide in concentrated hydrochloric acid to give 5-chlorobenzo-2,l,3-thiadiazole-4,7-dione (88KGS114). 

Benzimidazole-based glutaminyl cyclase inhibitors Benzimidazolyl-1,2,3 -triazoles Benzimidazolyl-1,3,4 -thiadiazoles... 

Glutaminyl cyclase (hQC) represents a new potential target for the treatment of AD, since inhibition of hQC prevents the formation of the Ap3(pE)-40,42-species. Novel molecules containing benzimidazole as the metal binding group connected to 1,3,4-oxadiazole as the central scaffold were identified. Benzimidazolyl-1,3,4-thiadiazoles and -1,2,3-triazoles display inhibitory potency in the nano-molar range [557]. 

Similarly, thiazol-2-amine, 5-ethyl-l,3,4-thiadiazol-2-amine, 5-methylisoxazol-3-amine. 1,2,4-triazol-3-amine and benzimidazol-2-amine give the corresponding heterocyclic systems on reaction with 2-aza-l-chloro-l,3-bis(dimethylamino)-3-phenylpropenylium perchlorate.490... 

By condensation of 2-amino-1,3,4-thiadiazoles with p-benzoquinone the 6-hydroxy[l,3,4]-thiadiazolo[3,2-a]benzimidazoles (356) are prepared (Equation (117)) <86IJC(B)1266>. 

The reaction of 3-(2-nitroaryl)-2,3-dihydro[l,2,4]oxadiazol-2-ones (385) with phosphorus pentasulfide in refluxing xylene transforms the oxadiazole ring into the thiadiazole ring concomitant reduction of the nitro group and closure of the imidazole ring affords [l,3,4]thia-diazolo[3,2-a]benzimidazoles (386). The reaction of l,3-dinitro-4,6-bis[(5-(l,l-dimethylethyl)-2-oxo-2,3-dihydro[l,3,4]oxadiazol-3-yl)benzene (387) is only partially successful and gives some 2-( 1,1 -dimethyl-ethyl)-5-[5-( 1,1 -dimethylethyl)-2-thioxo-2,3-dihydro-[l,3,4]oxadiazol-3-yl]-6-nitro-5-[l,3>4]thiadiazolo[3,2-a]benzimidazole (388) (Equation (132)) <88PS(36)139>. 

The reaction of 2-aminothiazoles (389 X = S) with 2-benzyl-5-chloro-2,3-dihydro[ 1,2,4]-thiadiazol-3-ones gives 3-(benzylaminocarbonylimino)thiazolo[2,3-c]thiadiazoles (390 X = S). With 2-aminobenzazoles the corresponding 3-(benzylaminocarbonylimino)-3/f-[l,2,4]thiadiazolo[3,4-fijbenzoxazole, -benzthiazole and -3,9-dihydro[l,2,4]thiadiazolo[4,3-a]benzimidazole derivatives (391) are obtained (Equation (133)) <94T7019>. 

Monocyclic and Bicyclic aromatic heterocycles such as imidazoles, thiazoles, thiadiazoles, oxazoles, oxadiazoles quinazolines, indoles, benzimidazoles, purines pyrido[43-d]pyri-midines, thiazolo[5,4-d]pyrimidines, thiazolo[4,5-d]pyrimidines, oxazolo[5,4-d]pyrimi-dines and thieno[2,3-d]pyrimidines are renowned pharmacophores in drug discovery. These special structures are well explained and exemplified in chemical compound libraries. In this chapter, several types of thiazole based heterocyclic scaffolds such as mono-cyclic or bicyclic systems synthesis and their biological activities studies are presented, which are not frequently present in books and reviews. We mention the first importance of synthetic route of various thiazole based compounds and their applications in medicinal chemistry in this chapter. 

Treatment of 2-phenyl-1,3,4-thiadiazole (121) with aroyl achlorides in aqueous sodium carbonate, bicarbonate, or cyanide has been claimed to yield 4-aroyl-5-hydroxy-2-phenyl-A -l,3,4-thiadiazolines (122). Analogous pseudobases derived from benzimidazole and dihydroisoquinoline have... 

A-(5-Ethyl-1,3,4-thiadiazol-2-yl)-4-[3-methy 1-5-( 1 -methyl-1 //-benzimidazol-2-yl)-1 -formazanyl]benzenesulfonamide, E-OOl 17... 

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