Hector s base

Diamino-1,2,4-thiadiazoles 66, also known as Hector s bases, are the oxidation products from iV-arylthioureas 65 a large number of examples of this type of reaction are known. Typical oxidants that give good yields are acidic hydrogen peroxide, nitrous acid, and iron(m) chloride (Equation 20) <1996CHEC-II(4)307>. 

The oxidation of amidinothioureas by a range of oxidizing agents to give 3,5-diimino derivatives is still one of the most versatile methods for the synthesis of N-linked derivatives (see Section 5.08.9.4). An alternative method which gives symmetrical derivatives is the oxidation of A-arylthioureas to produce Hector s bases which readily isomerize to give 3,5-diamino-l,2,4-thiadiazoles (see Section 5.08.9.2). 

A somewhat similar conversion was found when the 3-anilino-4-phenyl-5-imino-l,2,4-thiadiazoline (Hector s base) was heated with ammonia. 

The production and structure of Hector s bases have been the subjects of previous summaries1,2 and need not therefore be discussed in detail here. Recent results appear to favor their representation as 4-aryl-3-arylimino-5-imino-l,2,4-thiadiazolidines (35)53,54a... 

More decisive evidence is provided by the interconvertibility of N-aryl-JV-arylamidinothioureas (28) and Hector s bases by oxidation-reduction.63, B4,67b The former compounds are accessible (as salts) (i) by the condensation of arylthioureas (24) with arylcyanamides (23),63 (ii) by the extrusion of sulfur from the recently described40,41 s-diaryldithioformamidine hydrobromidesB4a (22), (tit) by the oxidation of arylthioureas (24) with 0.5 moles of hydrogen peroxide in the presence of mineral acids,B4a and (iv) by the mild reduction of Hector s bases by hydrogen sulfide in acid media.B4a The first of these four reactions limitB the structure of the products to the three alternatives 25, 28, and 30. Of these, 25 is excluded by the non-identity of the product with authentic67 N-phenyl-i -phenylamidinothiourea (25 R = Ph). The monosulfide structure (30) is not reconciled as readily with the observedB4a hydrolytic fission of the products into diaryl-guanidines (29) and thiocyanic acid as is structure 28. Indeed, as in the case of thioamides and nitriles (see Section II, C, 1), the present condensation may involve the primary formation of an intermediate diimido-monosulfide (30) and its isomerization to 28. 

Hector s bases571 thus leaves a choice between 35 and 36 for the structure of the latter. The decision in favor of 35 is based on the assumption that a free amino group rather than the anilino group is likely to be involved in the ring closure (28->35) it is supported by the fact that the chemical properties of Hector s bases are accounted for better in terms of structure 35 than 36 (see below). 

The connection between diaryldithioformamidines (22) and Hector s bases thus established suggests that the production of these heterocyclic bases from aromatic thioureas proceeds in acid media by way of primarily formed dithioformamidines (for references, see ref. 41) by the following sequence 24->22—>(23 + 24)- -28- -35. In particular, this interpretation accounts for the contrasting course of the oxidation of arylthioureas to Hector s bases in acidic polar solvents where intermediate disulfide formation is favored, and to benzthiazoles58 in nonpolar neutral solvents where a free-radical mechanism may operate. 

Reduction. The near-quantitative reduction of Hector s bases to s-diarylguanidines under various conditions34-30 53, 55 is well established. Milder reduction, by hydrogen sulfide at 26°, gives excellent yields of A-aryl-A-arylamidinothioureas (28),54a obviously by the familiar preferential fission of the heterocycle at the S—N(2) bond (see Section III,D,1) since these amidinothioureas (28) are cleaved to s-diarylguanidines and thiocyanic acid under the mildest hydrolytic conditions,54 their primary formation in aM reductions of Hector s bases is probable.54 ... 

Acidity. Hector s bases are mono-acid bases34-80,40,41>50,51 the presence of only one imino group in the preferred formulation 35 accounts well for the observed exclusive formation of monoalkyl, monoacyl, and mononitroso derivatives. The A-ethyl derivative30 is reducible to s-diphenylguanidine and ethylamine and is therefore regarded54 as 37, and the nitroso derivative as 38. 

Dost s keto compound. Treatment with concentrated hydrochloric acid converts Hector s base into a non-basic keto compound55 this is... 

The use of Hector s base (5-imino-4-phenyl-3-phenylimino-1,2,4-thiadiazolidine) as a sensitive reagent for carbon disulfide, and the nature of the product34,60 formed by the interaction of these compounds have been discussed by Feigl et ol.237... 

The preparations of 1,2,4-thiadiazoles and 1,2,4-thiadiazolidines from thioureas are well known and have been summarized in three reviews those of Bambas,188 Sherman,189 and Kurzer.170 Contained in these reviews are discussions of the controversies that surrounded some of the products, notably Hector s bases, which resulted from oxidation of substituted thioureas.171,172 Subjects covered in the above reviews, but too extensive to outline in detail here, are the oxidation of amidinothioureas to 3,5-diamino-1,2,4-thiadiazoles (71),173,174 the oxidation of phenylthiourea175 and of substituted amidinothioureas176 to 3,5-diimino-l,2,4-thiadiazolidines (72, Hector s bases), the reaction of thiopseudoureas with trichloromethanesulfenyl chloride to form 3-alkylthio-5-chloro-l,2,4-thiadiazoles (73),177 the reaction of thiopseudoureas with sodium thiocyanate and bromine178 and the oxidation... 

Additions of MPP and DMAD to Hector s bases (118) are considered to proceed via 6a-thia(SIV)-l,3,4-triazapentalenes (119), which decompose to give thiazoles (120) and the 7V-cyanoaniline 121.586... 

Cyclocondensation of alkyl(aryl)isothiocyanates with 4-aryl-3-arylimino-5-imino-l,2,4-thiadiazolidines (Hector s bases) 126 in the presence of strong bases leads to the formation of the corresponding (l,2,4-thiadiazolidinyl)thio-ureas 127 and heteropentalene stmctures 41 (Scheme 35), for which an isomerization equilibrium with the open form 42 was proposed (see Section 6.03.4.2) <1997IJB399>. 

The crystal structure of Hector s base (3) (78CC652) and a thiadiazolinedithione (4)... 

In the case of aniline, a weak base, no substitution occurs and (64) is obtained (75BCJ310). Oxidation of 1-phenylthiourea (66) with H2O2 gives Hector s base (3a Scheme 33). This... 

Hector s base (3a) forms a 1 1 adduct with carbon disulfide for which the alternative structures (70) and (71) were suggested by Butler (Scheme 34) (78JCR(M)0855). A recent X-ray analysis study has shown the correct structure of the adduct to be (72), readily explained in terms of an attack by the dithiocarbamate sulfur of (71) on the ring-sulfur atom. 

Hector s base (3a) and (73 Ar = C6H4Me-4) react with electron deficient alkynes (74) to give 2-arylaminothiazoles (76). The intermediacy of a 1,3-dipolar cycloadduct (75) has been suggested (75TL459) to explain this result (Scheme 35). In order to provide support for the intermediate formation of (75), the reactions of 2-imino-3,4-diphenylthiazoline (77) with alkynes were studied. No 1,3-dipolar addition product (78) could be isolated instead, simple addition products (79) were obtained in high yields (Scheme 36). 

In contrast to the formation of Hector s base (3a) by the oxidation of 1-phenylthiourea, oxidation of l-phenyl-3-methylthiourea and 1,3-diphenylthiourea give thiadiazole (86 ... 

Moderate yields of thiadiazoles (255) also have been obtained by the thermolysis of mixtures of thioamides (253) and A-sulfinylsulfonamides (259 Scheme 91) (62AG135). The manner in which the proposed intermediate (260) is converted into (255) has not been discussed and the mechanism of this reaction deserves further study. TV-Arylthioureas (261) form 1,2,4-thiadiazole derivatives (73) ( Hector s bases ) in good yields when oxidized with acidic hydrogen peroxide or other oxidizing agents (nitrous acid, iron(III) chloride) as indicated in Scheme 92 (65AHC(5)119). Evidence for the intermediate formation of dithio-... 

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). 

Oxidation of N-arylthioureas (261) with acidic hydrogen peroxide produces Hector s bases (73) which readily isomerize under basic conditions to afford 3,5-diamino-l,2,4-thiadiazoles (84 Scheme 146) (65AHC(5)119) (also see Scheme 92). A variety of 3-amino-and 3,5-diamino-l,2,4-thiadiazoles (325) also have been obtained by the treatment of iminocarbonates (322) with chloramine at low temperature, as illustrated in Scheme 147 (also see Scheme 115) (76EGP119791). 

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