Dithioles and Related Systems

When 4-phenyl-l,3-dithiol-2-one is heated with mercuric acetate, a substitution reaction occurs leading to 4-acetoxymercuri-5-phenyl-l,3-dithiol-2-one. Treatment of this product with iodine in chloroform solution brings about displacement of the acetoxymercuri-group by iodine. 4-Bromo-l,3-dithiol-2-one (54) is conveniently prepared from l,3-dithiolan-2-one (53) by the sequence shown. A detailed analysis has been made of the n.m.r. spectra of l,3-dithiol-2-one and the corresponding 2-thione.  

As already noted in this Chapter, 4,5-dialkyl-l,3-dithiole-2-thiones are formed, with l,2-dithioIe-3-thiones, when thioketones are treated with sulphur and carbon disulphide in the presence of a base.  

An interesting series of compounds of general structure (56 X or Y = S or Se) has been prepared from phenylacetylene by the route shown, via the anions (55 X = S or Se). The four possible products all react with 

Reduction of l,3-dithiole-2-thione and its benzo-derivative with lithium aluminium hydride gives ethanedithiol and thiocatechol respectively, but similar reduction of the cyclohexene compound (59) replaces the thio-carbonyl group by a methylene group.  

Related structures, for example (62), are prepared by condensation of 2-piperidino-l,3-dithiolium salts with active-methylene compounds.  

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This section is divided into reactions of fully unsaturated rings like 1,3-dithiolylium ions, mesoionic 1,3-dithiolones, l,3-dithiol-2-ones and l,3-dithiole-2-thiones, and reactions of the saturated 1,3-dithiolanes. As a consequence of the positive charge in 1,3-dithiolylium ions, the main reactions of this class of compounds consist of nucleophilic attack at the 2-position, whereas the mesoionic 1,3-dithiolones undergo cycloaddition reactions. Reactivity of the benzo ring in benzo-l,3-dithiole and related systems has not been studied to any extent. 

Dithioles and Related Systems. - Base-catalysed condensation of the 1,2-dithiolium salt (195) with ethylidenemalononitrile yields the dithiole (196). The action of potassium borohydride on the enamine (197) results in the rearranged thiopyranthione (199), presumably via compound (198). Deprotonation of the bisulphate (200) or heating the tosylhydrazone (201) produces the thienothiophen (202). It has been reported that the dihydrodithiolone (203) is desulphurized by hexaethylphosphoric triamide to yield the thietanone (204). 1,2-Dithiole-3-thiones (205 X = S =... 

The high level of activity in the synthesis of tetrathiafulvalenes (TTFs) and related systems has continued and several major reviews of the area have appeared <95AHC(62)249, 95MI1481,96SR(18)1>. A mechanistic study on the P(III) mediated coupling of 1,3-dithiole-... 

Several workers have studied the reactions of l,2-dithiole-3-thiones and related systems with acetylenic esters. The thiones (395), for example, react with DMAD to give 2-thioacylmethylene-l,3-dithioles (396), which may arise through a concerted 1,3-dipolar addition to the S—C=S moiety. These adducts undergo further reaction with DMAD, yielding thiopyran-4-spiro-2 -(l,3-dithioles) (397) (Scheme 62). Similarly, the reaction of 5-phenyl-l,2,4-dithiazole-3-thione (398) with... 

Examples of these systems are the l,2-dithiole-3-thione 43 and the type A mesoionic l,3-thiazolium-4-olate 44. Important members of this class are the tetrathiafulvalenes (TTFs) 45 and related systems, which have been studied extensively because of their potentially useful electrical properties . 

The chemistry of the 1,2-dithioles and related compounds was covered in the first edition of Comprehensive Heterocyclic Chemistry (CHEC-I), and a review, published in 1990, of some systems containing the 1,2-dithiolane ring <90SR257>. Reviews of other 1,2-dithioles were published in the early 1980s <80SRi, 82AHC(3i)63>. Since 1985 there has been a marked increase in published applications of 1,2-dithioles. 

The 1,2-dithiole system and related compounds possess two adjacent sulfur atoms in a five-membered ring. The types are known respectively as 1,2-dithiolanes (1), 1,2-dithioles (2), l,2-dithiol-3-ones (3a), l,2-dithiole-3-thiones (3b), 3-iminodithioles (3c), l,2-dithiol-3-ylidenes (3d) and 1,2-dithiolylium (4) ions. 

Some simple dithiolethiones, including the parent (3b) and 5-aryl derivatives, have been isolated from Brassica species, and some Streptomyces strains produce four antibiotics which possess pyrrolo[3,2-c][l,2]dithiole skeletons (174a-d). Some of these have been synthesized (B-66MI43100,77JOC2891). Lipoic acid (29) is a growth factor and an essential component of enzyme systems involved in oxidative decarboxylation of pyruvic and related acids (B-61MI43101). 

The RSH/RSSR interconversion is well known in organic chemistry due to its biological importance in systems like cysteine-cystine, glutathione and the corresponding disulfide, and Q -lipoic acid and related dithiol. 

All non-heme iron containing ribonucleotide reductases are also inhibited by hydroxyurea and related hydroxamates, while the adenosyl-cobalamin-dependent reductases are not affected (27, 156). The inhibition by these reagents can be partially reversed by excess Fe+2 or dithiols. Reaction of ribonucleotide reductase of E. coli with [14C]hydro-xyurea inactivated only the B2 subunit and this inactivation was not reversed by removal of the radioactivity (157). Inactivation by hydroxyurea does not affect the iron content of protein B2, but involves the destruction of the stable free radical (66,67). Reactivation can be accomplished by removal of the iron and reconstitution of apoprotein B2 with Fe+2. Hydroxyurea has been demonstrated to be a powerful radical scavenger in another system (158). 

Pacquer et al. also recognized a second series of intensely colored 1 1 adducts, the trithiapentalenes 153, from benzyne and 5-aryl-l,2-dithiole-3-thiones (151).93 Although very little of 153 (Ar = Ph) was obtained (< 1%), p-anisyl, p-tolyl, and p-chlorophenyl compounds were formed in higher yields. Unsuccessful attempts to achieve the conversion 152 - 153 render more likely an independent pathway for the formation of 153, e.g., one involving an initial 1,2-cycloaddition of benzyne to the exocyclic C=S bond of 151. Derivatives of the related l,2,4-dithiazole-3-thione system 160 and benzyne also afford two series of 1 1 adducts 161 and 162 corresponding to 152 and 153, respectively.93... 

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