1,2-Dithiole-3-thione, methylation

Dithiole-3-thione, methylation of, 391 Di-(trimethyisilyl) amine, reaction with A-4-thiazoline-2-thione, 396 Diuretic sulfonamide, 414 Diuretic properties, 150, 152 Dithiobiuret, 85... 

C3S2 s s — — — l,2-Dithiolane-4-carboxylic acid 3-phenyl-l,2-dithiolylium iodide 4-methyl-1,2-dithiole-3-thione ... 

Dithiole-3-thione, 4-methyl-bond distances, 6, 785 synthesis, 6, 804... 

Many papers deal with both analytical determination and cathodic transformations of thiones (21). Thus, a four-electron reduction of OLTIPRAZ [4-methyl-5-(2-pyrazinyl)-l,2-dithiole-3-thione] produces several species that could account for the schistosomicidal activity of metabolites of the starting compound. The first two-electron reduction (in aqueous media) affords the scission of the S —S linkage and the thus formed dianion can be readily [197] alkylated by common alkyl halides. Let us note that the cathodic behavior of structure (21) was shown to be strongly influenced by the nature of substituents and particularly [198] by the electron-donating ability of Rh... 

These spectra were routinely obtained for most of the compounds discussed in forthcoming sections. Specific studies were performed on selected compounds such as (i) (+)-(S )-4,5,6,7-tetrahydroimidazo-9-chloro-5-methyl-6-(3-methyl-but-2-enyl)imidazo [4,5,1 -jk [1,4] benzodiazepin-2(l//)-thione (9-chloro-TIBO)187 and (ii) series of metal chelates derived from l,2-dithiol-3-thion-4,5-dithiolate (dmt)188. The equilibria between 2-ethoxycarbonylthiolane-3-thiones and their (Z)-enethiol tautomers were also studied by these techniques189. It was found that the equilibrium is largely shifted in favor of the enethiols. NMR was also used to study the syn-anti conformational equilibria of seven A-(l-methoxycarbonylethyl)-A4-thiazoline-2-thiones with S conformation of the chiral rotor (43)190. A variety of substituents were used. 

Syntheses and X-ray structures have been reported for (53) [94T11205] and (54) [95MI645], The preparation and non-linear optical properties of 2-imino-l,3-dithioles (55) have been described [95MI35] and the dimeric derivatives (R3 = p-phenylene) have also been reported [94BSF774]. The product (56), obtained from reaction of 4-methyl-5-phenyl-l,2-dithiol-3-thione with DMAD, undergoes cycloaddition with a further molecule of DMAD to afford the spiro compound (57) whose structure is confirmed by X-ray methods [94KGS908]. 

Reaction of 4-fluoro5-5-(l,l,2,2-tetrafluoroethyl)-3//-dithiole-3-thione with 2equiv of Na2S affords 3,4-difluoro-2-mercapto-l,6,6aA-trithiapentalene after an acidic work-up. Further reduction with Na2S gives 3,5-difluoro-4-mercapto-2//-thiopyran-2-thione 507 in >30% overall yield. Methylation of the Na salt of the pentalene affords an 1 1 mixture of methylsulfanyl derivatives of a 2//-thiopyran-2-thione 508 and 4//-thiopyran-4-thione 509 (Scheme 190). DFT calculations predict the stability sequence for the thiones is 507 > 508 > 509 <2006JFC(127)774>. 

An unusual synthesis of 2-alkylthio-TA 41 consists in the ring enlargement of l,2-dithiole-3-thiones 40 in the reaction with sodium cyanide, followed by methylation (88JHC1223) (Scheme 9). The suggested mechanism is confirmed by an increase in yield of TA 41, when excess thiocyanate ion is added. 

These structures may be named as follows 7, l-(l,2-benzodithiol-3-ylidene)propane-2-thione and 8, 6-(5-methyl-l,2-dithiol-3-ylidene)-2,4 -cy clohexadiene-1 -thione. 

Carbon oxysulfide and sodium hydride react with 4,5,6,7-tetra-hydro-l,2-benzodithiole-3-thione in dimethyl sulfoxide (DMSO), giving a dianion (28) which, by action of methyl iodide, gives a dithiolic thio ester (29). On standing, 28 partly isomerizes to 30, which, by methylation gives the dithiolone 31.23... 

Methyl or 5-methylene substituents in a l,2-dithiole-3-thione are particularly reactive. In the presence of <-amyloxide, carbon disulfide reacts with such groups giving a dianion which, when treated by methyl iodide, forms a bis(methylthio)trithiapentalene (Scheme... 

Sulfur atoms in positions 1 and 6 in the trithiapentalene system may sometimes react as the thione sulfur atom of l,2-dithiole-3-thiones. For instance, 2,4-diphenyl- and 2,3,4-triphenyl-l,6,6a IV-trithiapentalene add methyl iodide (Eq. 34).76... 

Let us now consider the bond lengths between two sulfur atoms. The following values have been found for the S8 stable molecule, 2.12103 and 2.037 A104 106 for bis-2-iodoethyltrisulfide, 2.05 A101 and for 4-methyl-l,2-dithiole-3-thione, 2.04 A.107... 

For alkanes, alkenes and their aryl derivatives, direct sulfurization gives thiones (3b). Typical examples are the preparation of 4-methyl- (10), 5-(4-methoxyphenyl)- (129) and 4-phenyl-l,2-dithiole-3-thiones (71) and benzo-l,2-dithiole-3-thione (77b) (Scheme 22) (B-66MI43100). 

In l,6,6aA4-trithiapentalenes, the sulfur atoms numbered 1 or 6 are much less reactive than the thione sulfur of l,2-dithiole-3-thiones. Nevertheless in some cases they may be alkylated leading to a compound which may be considered as a dithiolylium cation. Methyl... 

Carbanions derived from 5-alkyl-l,2-dithiole-3-thiones react with carbon oxysulfide or disulfide, or with phenyl isothiocyanate, to give dianions which can be methylated as shown in Scheme 8. 

Thione groups can often be eliminated by oxidation probably the sulfinic acid is the intermediate. Sometimes the sulfinic acid can be isolated (e.g., 740 741), but more often it spontaneously loses SO2. In this way, thiazoline-2-thiones give thiazoles, l,2-dithiole-3-thiones 742 are converted into 1,2-dithiolylium salts 743, l,3-dithiole-2-thiones 744 into 1,3-dithiolylium salts 745, 1,5-disubstituted imidazole-2-thiones into imidazoles <2003JHC229>, and 3-mercapto-l,2,4-triazoles into the parent triazole <2006S156>. In the pyrazole series, 746 also loses an A-methyl group to yield 747. 

Unsymmetrical hexathioorthooxalates are obtained in good yields (60 to 90%) by coupling two different l,3-dithiole-2-thiones in the following manner [59] Methyllithium is added to the first l,3-dithiole-2-thione S-alkyl-ation occurs to form 21. A second 1,3-dithiole is reacted with the adduct (21), and the resulting product is alkylated with methyl iodide. The hexathioorthooxalate obtained in this way (22) can be converted to a tetra-thiafulvalene as outlined above [36,37] (75 to 95%). The overall sequence is shown for the preparation of benzodimethyltetrathiafulvalene (23) in Scheme 8. 

Potential 2-hydroxy- and 2-mercapto-l,3,4-thiadiazoles have been examined both by infrared and by ultraviolet spectra in the solid state and in solution by Sheinker et They concluded that these compounds exist in the 2-oxo and 2-thione forms, respectively. To 2,5-dimercapto-l,3,4-thiadiazole the 2-mercapto-5-thione structure (155) was given. The structure of this compound has been the subject of some controversy. Stanovnik and TiSler have added some valuable arguments to the discussion. They measured the pKfl values of 155, its iV-methyl, iV -phenyl, and iV -phenyl-/S-methyl derivatives (156), and of the conjugate acids of these and the S-methyl derivative (pKn ) (Table III). In all compounds 156 with R = H, the infrared spectrum showed an absorption band near 2300 cm characteristic of the SH group. They also had pK i values near —1.5, Avhich in connection with the infrared evidence was taken as characteristic of an SH group in this situation. Since the 2,5-dithiol structure is excluded by ultraviolet spectral evidence, the 2-mercapto-5-thione structure (155) seems rather well established. It has previously been shown bj Thorn to predominate in chloroform solution, whereas he concluded that the dithione form (157) should predominate in ethanol solution. However, the pK i value for 155, — 1.36, makes it rather probable that Thorn used the monoanion of 155 instead of the acid itself for spectral comparison, and in that case his conclusions have a very weak foundation. 

When an N-substituent at C-2 of 1,3-dithioles was replaced by an S-substituent, a similar reaction sequence led to formation of the bis(2,3-dithiabutane-l,4-diyl)TTF 686. Thus, methylation of the l,3-dithiole-2-thione 681 with MeOTf afforded the corresponding salt 682, which after reduction with NaBH4 produced the 1,3-dithiole 683. 

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