1.2.4- Thiadiazole Dimroth rearrangements

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. 

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. 

Examples of the Dimroth rearrangement (Section IV, F) include several s3mtheses of monocyclic triazoles from other heterocyclic systems (cf. Scheme 25). Triazole-5-thiols can be prepared by treatment of 5-amino-l,2,3-thiadiazoles with bases.A similar base-induced rearrangement of sydnoneimines provides a synthesis of 4-hydroxy-triazoles. ... 

Nitrogen-15 NMR has been used to study the course of acylation and carbamidization reactions of 3-amino-5-methylthio-1,2,4-thiadiazole (3). Using a N label in the 2-position of (3), its reaction with hard nucleophiles was found to proceed via initial reactioa on the 2-position followed by a Dimroth rearrangement to give the acylated product (4) with the N label in the exocyclic position. The reaction of (3) with soft nucleophiles, such as methyl isocyanate occurs directly on the exocyclic nitrogen to give the urea (5) (Scheme 1) <84CHEC-l(6)463 >. 

The positive ion mass spectrum of 3-amino-5-methylthio-l,2,4-thiadiazole (3) has also been studied using N isotopes. When a N label was incorporated into the 2-position or the exocyclic nitrogen a 13-16% incorporation of the N label was found in the mercaptothiazirinium ion (6) (Equation (1)). This incorporation is explained by a series of Dimroth rearrangements (Scheme 4) <86MI 408-01 >. 

Alkylation of 5-amino-1,2,4-thiadiazoles (17) with methyl iodide leads to N-4 derivatives of type (18) which undergo a Dimroth rearrangement to (110) on warming in ethanol when R = H (Scheme 26). When R = methyl, phenyl, or benzyl the reaction is severly hindered <84CHEC-I(6)463>. In contrast, benzhydryl and trityl chlorides (which are harder electrophiles) alkylate (17) at the 5-amino function to give compounds of type (109) (Scheme 26). 

Methylation of 3-amino-5-phenyl-l,2,4-thiadiazole (111) with trimethyloxonium tetrafluoro-borate produces the N-2 quaternary salt (112) which on basification undergoes a Dimroth rearrangement to give the 3-methylamino derivative (113) (Scheme 27) <82AHC(32)285>. By analogy with 5-amino-l,2,4-thiadiazole (17) (R = H), the 3-amino-1,2,4-thiadiazole (111) is alkylated by benzhydryl and trityl chlorides to give (114) (Scheme 27). 

Methylation of 5-amino-l,2,4-thiadiazoles (16 R = H, Ph), leads to N-4 derivatives (19) which on warming in ethanol undergo a Dimroth rearrangement to 5-methylamino-l,2,4-thiadiazoles (20) when R = H. Available evidence suggests that the isomerization proceeds by the sequence shown in Scheme 12. Ethylation of (16) proceeds in low yield and no reaction is observed when R = Ph. Introduction of higher alkyl, allyl and benzyl groups is also unsuccessful. 

The Hector s bases (73) undergo a Dimroth rearrangement, presumably via (264), to the symmetrical Dost s bases (84) when heated under alkaline conditions. Oxidation of N -alky 1-iV-arylthioureas affords the symmetrical thiadiazoles (265) directly whereas the products obtained from N,N - disubstituted thioureas (266) depend on the nature of the substituents (80JCR(S)407). 

Dimroth rearrangement also occurs between the 5-mercapto-l,2,3-triazoles (109) and the 5-amino-l,2,3-thiadiazoles (110). If the thiadiazoles (110) are heated in basic solvents they are converted into the triazoles, whereas the reverse reaction is observed in acidic media (67LA(710)118, 69CB417, 72ACS1243). Thermal equilibria of thiadiazoles and triazoles, with both isomers present, have been reported (62Acs(B)1800, 66CB1618). 

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