Isothiazoles, hydrolysis

Addition of nucleophiles to the cyano group of cyanothiadiazole under basic conditions takes place with unusual ease <88AG(E)434,94ACS372). Hydrolysis to the amide, for example, can be effected at 0°C in the presence of a catalytic amount of sodium hydroxide or basic ion-exchange resin. At reflux temperature, hydrazine and monosubstituted hydrazines convert 3,4-dicyano-l,2,5-thia-diazole into the l,2,5-thiadiazole[3,4-. The base-catalyzed addition of acetone to cyanothiadiazole forms an enamino ketone, used as a key intermediate for the synthesis of a number of heterocyclic ring systems, e.g. isothiazole, isoxazole, pyrazole, pyrimidine, and thiazole <77H(6)1985>. 

Isothiazole-5-carboxylic acids have usually been synthesized from the lithium derivatives and carbon dioxide, or by alkaline hydrolysis of nitriles obtained from 5 hromo compounds and cuprous cyanide.3,70... 

Acetylisothiazoles have also been obtained from 5-cyanoisothiazoles and methylmagnesium iodide and by hydrolysis of j8-ketoesters derived from isothiazole-5-carboxylic esters.70... 

N-Acyl saccharins (13) in part resemble iV-alkyl saccharins in their reactions. From the hydrolysis of 3-oxo-2-acetyl-6-chloro-2,3-dihydro-benz[d]isothiazole-1,1-dioxide (64) with a base/alcohol mixture one obtains iV-acetyl-4-chloro-2-sulfamoylbenzoic acid (65). On heating with base the acetyl group is hydrolyzed off.180... 

Alkaline hydrolysis of 5a appears to pass through l,244 leading to the same final product (o-carboxybenzenesulfonamide). The monomethyl and ethyl derivatives (9 R = Me, Et) hydrolyze slowly to 1 in dilute alkali,13 3-(o-carboxyanilino)benz[d]isothiazole-l, 1-dioxide (77) and functional derivatives form a tetracyclic system (78) on treatment with... 

Another application of the well-known cyclization of ortV o-substituted benzenesulfonamides consists in the treatment of 415 (R =NR2, R = Me) with Et30Bp4 followed by aqueous H2SO4 affording good yields of benz-isothiazol-3-one 1,1-dioxides 416. Their alkaline hydrolysis afforded 415 (R = OH, R = R = H), which is stable at neutral pH but recyclizes to 416 under even mild acidic conditions (pH <4) <1999T237>. 

Isothiazole-A-carboxylates are obtained starting from amides by first forming the oxathlazolone by means of ClCOSCl. Condensation with methyl acetylene dicarboxylate followed by hydrolysis and decarboxylation completes the sequence. ... 

The reaction of (148) with glycol and hydrogen peroxide gave (149). Compound (19b) has been reduced with liAlH4 to the corresponding alcohol, which was converted into the aldehyde and bromomethyl and aminomethyl derivatives that are of pharmaceutical interest. A mild method for the hydrolysis and decarboxylation of various amides of methyl 3-aminothiophen-2-carboxylates has been developed. Thermal decomposition of (150) led to cleavage of the thiophen ring, with extrusion of sulphur and formation of the isothiazole (151). ... 

Thienof3,2-d]isothiazoles. - Ethyl 4-amino-3-methylthienoT 3,2-db isothiazole-5-carboxylate (47 R =Me,R =NH2,R =C00Et) was obtained by NaOEt cyclisation of (46 R=CH2COOEt). Compounds (46 R=Me, 2 , 2 6 1-4) were also prepared. Diazotisation, reduction and hydrolysis of (47 R1=Me,R2=NH2,R3=COOEt) gave (47 R1=Me,R2=H, R3=COOH) which could be decarboxylated to the parent 3-n ethyl-thieno(3 2-d]isothiazole (47 R1=Me,R2=R3=H). The latter nitrates or brominates at the 5-position. Reduction with hypophosphorous... 

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