1,2,3-Thiadiazole rearrangement

Thiadiazoles rearrange to variously substituted 1,2,3-thiadiazoles (83CC588). Many 5-azido-1,2,3-thiadiazoles rearrange to 1,2,3,4-thiatriazoles (Scheme 9) (88BSB163). 

There are many related examples which are now known as the general Dimroth rearrangement. For example, 3-ethylamino-l,2-benzisothiazole (419) is in equilibrium in aqueous solution with the 2-ethyl-3-imino isomer (420) <72AHCf 14)43). Dimroth rearrangements are known in the 1,2,4-thiadiazole series (421- 422), and in the 1,3,4-thiadiazole series as products of reactions of halogeno-l,3,4-thiadiazoles see Section 4.02.3.9.1 <68AHC(9)165). For a similar example in the 1,2,3,4-thiatriazole series, see Section 4.02.3.1.9. 

Pyrazblin-5-one, 3-alkyl-(l,2,4-thiadiazol-5-yl)-reactions, 6, 483 2-Pyrazolin-5-one, 3-amino-tautomerism, 5, 215 2-Pyrazolin-5-one, 4,4-diazido-rearrangement, 5, 720 2-Pyrazolin-5-one, 3-hydroxy-tautomerism, 5, 215 2-Pyrazolin-5-one, 3-methyl-1 -phenyl-reactions, 5, 252... 

According to REM, hydrazine hydrate Is reacted with 2 mols of ammonium thiocyanate to produce 1,2-bislthlocarbamoyl) hydrazine which by loss of ammonia and rearrangement produces 5-amino-2-mercapto-1,3,4-thiadiazole. That compound is acetyied with acetic anhydride. 

An interesting rearrangement was found by Davies and Kirby (1967) in the diazo-tization of 7-amino-benzothiazole (6.68). As Scheme 6-45 shows, the diazonium ion formed initially rearranges under hydrolytic conditions into 7-amino-l,2,3-benzo-thiadiazole (6.69). 

A rearrangement involving a fluctuating 1,2,3-thiadiazole ring has been found by Haddock et al. (1970) after diazotization of 7-amino-6-substituted 1,2,3-benzothia-diazoles (Scheme 6-46). 

The thermally induced rearrangements in the furoxan series have also been found. In particular, the transformation of 3-R-substituted 4-(3-ethoxycarbonylthioureido)-l,2,5-oxadiazole 2-oxides into derivatives of 5-amino-3-(a-nitroalkyl)-l,2,4-thiadiazole and into (5-amino-l,2,4-thiadiazol-3-yl)nitroformaldehyde arylhydrazones has been reported (Equation 8) <2003MC188>. 

L abbe has studied the rearrangement reactions of 1,2,3-thiadiazoles to differently substituted 1,2,3-thiadiazoles <1983CC588>. He also studied many 5-azido-l,2,3-thiadiazoles 33 that rearranged to 1,2,3,4-thiatriazoles 34 (Equation 5) <1988BSB163>. He even found that l,2,3-thiadiazole-4-carboxaldehydes 35 upon treatment with amines underwent thermal rearrangement to 1,2,3-triazoles 36 (Equation 6) <1993J(P1)1719>. 

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>. 

Mesoionic derivatives are generally synthesized from the parent 1,2,3-thiadiazoles. A new method based on the rearrangement of oxadiazoles under reductive conditions has been reported. For example, the oxadiazole 70 when... 

A good method for the preparation of substituted 3,5-diamino-l,2,4-thiadiazoles is the rearrangement of dithiazolium cations with sodium azide <2004HOU277>. If the amino groups at the 3- and 5-positions are different, then a mixture of isomeric 3,5-diamino-l,2,4-thiadiazoles is obtained. 

Amino derivatives of 1,2,4-oxadiazoles, isoxazoles, and 1,2,5-oxadiazoles interact with phenyl isocyanate to produce various 3-substituted 5-amino-l,2,4-thiadiazoles, via intermediate thioureides which can be isolated. The tendency to rearrange follows the order 1,2,4-oxadiazoles, isoxazoles, and 1,2,5-oxadiazoles <1996CHEC-II(4)307>. 

A novel approach to 1,2,4-thiadiazoles 112 is based on the monocyclic and cascade rearrangement of 1,2,5-oxadiazole-2-oxides 111 <2004PAC1691>. Thus, /V-oxidcs 110 upon treatment with ethoxycarbonyl isothiocyanate undergo cascade rearrangement to give 1,2,4-thiadiazoles 112 via intermediate 111 (Scheme 13). 

Thiadiazoles are also obtained when the thermolysis is carried out in the presence of isocyanates and carbodiimides <1996CHEC-II(4)307>. There have been no new reports of this type of rearrangement since the publication of CHEC-II(1996). 

Electrophilic substitution reactions on the carbon atoms of 1,3,4-thiadiazoles are rare due to the low electron density of ring carbons. G-Acylation can be accomplished via rearrangement of intermediate W-acylthiadiazolium salts while radical halogenation can give chlorinated or brominated 2-halo-5-substituted thiadiazoles. Examples can be found in CHEC(1984) <1984CHEC(6)545> and in Houben-Weyls Science of Synthesis <2004HOU(13)349>. 

The 5-thio-substituted l,3,4-thiadiazole-2(377)-thiones 75 react with iV-methyl-C-phenylnitrilimine in a regiospe-cific 1,3-dipolar cycloaddition to form not the expected cycloadducts 76 but rather the rearranged products 77 and 78 in 16-28% yields (Scheme 6) <1998AJC499>. 

Heating of a solution of 5-ethyl-3-phenyl-l,3,4-thiadiazol-2(377)-imine 85 in aq. NaOH to 80°C for 5h gave the 5-ethyl-2,3-dihydro-2-phenyl-l/7-l,2,4-triazole-3-thione 86 via Dimroth rearrangement (Scheme 7) <2002HCA1883>. Nucleophilic attack of the hydroxide on the electrophilic C-5 resulted in ring opening and, after rotation around the C(2)-N(3) bond and subsequent recyclization, triazole thione 86 formed. 

The allylation of thiadiazole-2-thione 114 with ally 1 bromide gave as the main product the N-allyl derivative 115 with trace amounts of the corresponding S-derivative 116 (Equation 36) <2003CHE228>. Furthermore, it was shown that refluxing the thiadiazole 116 in DMF (3h) gave thiadiazole-2-thione 115 via a thio-Claisen rearrangement. 

The sulfide derivative of furocoumarin based natural products can be synthesized by treatment of a thiadiazole 107 with KO-f-Bu and an organohalide in an one-pot operation. This process presumably involves the generation of a phenolate 108 and is followed by an intramolecular proton shift and a rearrangement to give an alkynethiolate 109, which undergoes a sequence of intramolecular proton shift, cyclization and alkylation to lead to the furocoumarin product. The thiadiazole, in turn, can be prepared by reaction of the corresponding acetyl precursor with carbethoxyhydrazine, followed by treatment with thionyl chloride . 

In the presence of triethylamine, the reaction of 2-amino-5-methyl[l,3,4]thiadiazole 134 with 2-benzyl-5-chloro-[l,2,4]thiadiazol-2-one 135 gives 3-(benzylcarbamoylimino)-6-methyl-3//-[l,3,4]thiadiazolo[2,3-c][l,2,4]thiadiazole 138. Presumably, the first-formed intermediate 136 rearranges through the thiapentalene intermediate 137 to the fused thiadiazole product 138 (Scheme 10) <1994T7019>. 

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