2-Amino-5- thiadiazole

The reactions of 2-amino-1,3,4-thiadiazoles and diethyl 1-ethoxyethyli-denemalonate in diglyme at 140°C for 20 hr gave 7-methyl-1,3,4-thiadia-zolo[3,2-a]pyrimidine-6-carboxylates (672) in 14-25% yields after column chromatography (86FES737). Reactions in ethanol or dimethylacetamide were unsuccessful. 

For instance, the treatment of 2-aminothiazole or 2-amino-1,3,4-thiadiazole with a equimolar amounts of appropriate (hetero)aromatic or aliphatic aldehydes in the presence of an excess of mercaptoacetic acid under refluxing in anhydrous benzene gave diverse 2-substituted 3-(2-thiazolyl)- and 3-[2-( 1,3,4-thiadiazolyl)]-4-thiazolidinones 115a or 115b, respectively (Scheme 54). 

The novel heterocyclic system 92 has been prepared by reaction of 2-amino-1,3,4-thiadiazoles 91 with either l-(haloalkyl)pyridinium halides 89 or N,N -methylenebis(pyridinium) dihalides 90. A mechanism for the formation of 92 was proposed and involved a series of specific proton migrations, bond-breaking and bond-forming processes <98EJOC2923>. 

The sulfonylurea hypoglycemic agents, as noted in Chapter 2, also trace their ancestry to the sulfonamides. It is of interest that activity is retained when a substituted 2-amino-1,3,4-thiadiazole replaces the urea function. Reaction of isobutyryl chloride (123-1) with thiosemicarbazone (123-2) leads initially to the transient 1,2-diacyUiydrazine (123-3). This apparently cyclizes spontaneously to thiadiazine (123-4) under reaction conditions. Acylation with p-methoxysulfonyl chloride (123-5) affords the oral hypoglycemic agent isobuzole (123-6) [134]. 

Amino-1,3,4-thiadiazole or 2-lmino-1,3,4-thiadiazoline, called by Freund Tmidothio-biazolin", HC-S-C-NH. or HC-S-C NH. 

Diaminothiadiazole and derivs 5 Dl 145 5 -nitrosoamino-2-amino-1,3,4-thiadiazole 5 D1145... 

Amino-l,2,5-thiadiazole is chlorinated or brominated at the 4-position at 20°C in acetic acid. 3-Methyl-1,2,5-thiadiazole can also be chlorinated in the 4-position (68AHC(9)107). Bromination of 2-amino-1,3,4-thiadiazole succeeds in the 5-position (65ACS2434). 

CjHjN S, rnw 130.13, N 43.06%. Yel crysts, mp 220°(dec). Was prepd by treating 2-amino-1,3,4-thiadiazole hydrochloride with aq Na nitrate while cooling... 

The reaction of unsubstituted 2-amino-1,3,4-thiadiazole (131) with 1,3-dicarbonyl compounds is dependent on the nature of the dicarbonyl compound (Scheme 13). Thus, reaction of (131) with pentane-2,4-dione gives the 4,6-dimethyl-2-thiocyanatopyrimidine (132). The formation of (132) may proceed via the cation (132a). With ethyl acetoacetate, however, a mixture of (133) and (134) is formed, (133) also being converted into (134) on heating. 

The unsubstituted 1,3,4-thiadiazole (3, R = H) was described in 1956 by Goerdeler et al. They transformed 2-amino-1,3,4-thiadiazole (4, R = H) into the 2-bromo compound (5, R = H) by a Sandmeyer reaction, and by hydrogenation of the latter with Adams catalyst the parent compound of the series was obtained as a colorless solid, m.p. 42-43°, b.p. 204-205°. Jensen and Pedersen prepared the same... 

A patent describes the preparation of 2-amino-5-nitro-l,3,4-thiadiazole (142) by nitration of 2-amino-1,3,4-thiadiazole (4, R = H) with fuming nitric acid at 40°. However, the product has the same melting point as the 2-nitramino-1,3,4-thiadiazole (46, R = H) described by Kanaoka, which was obtained under very similar conditions. Since the structure of 46 (R = H) was demonstrated by reduction to 2-hydrazino-l,3,4-thiadiazole, the structure 142 may be viewed with some skepticism. 

Diaminopyridinium salts also cyclize with acylating agents to give s-triazolo[l,5-a]pyridines (Eq. 14).138,143 Applications of this reaction to aminodiazines,144 2-amino thiazoles,145 146 2-amino-1,3,4-thiadiazole,147... 

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>. 

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