Dithiazoles, synthesis

Imidazo[2,l-c][l,2,4]dithiazole-3-thione, 5,6-dihydro-synthesis, 6, 1016 Imidazo[ 1,2-c]hydantoin synthesis, 6, 991... 

The sole recent example of this synthesis involved the complex reaction of 1,2-benzenediamine (348) with 4-chloro-5-cyano-l,2,3-dithiazol-l-ium chloride (349)... 

The general synthetic methodology to benzo-fused dithiazolyl radicals has been extended to the synthesis of di- and tri-radicals. Of these the benzo-1,2 4,5- /h.v(l,3,2-dithiazole) system has been studied in its full range of oxidation states, i.e. 34, 35 and 36 (Scheme 9). 

A great advantage of this method is the synthesis of bis(l,2,3-dithiazoles) from diaminodithiols (1997JA12136, 1999CM164, 2000JA7602). Reduction of radical cations formed with PhsSb led to neutral heterocycles 122 and 123 as air-stable crystalline solids (Scheme 61). 

Synthesis of 1,2,3-dithiazoles is the most extensively studied. The widely used and very long-known Herz reaction of arylamines with S2CI2 to give benzo-l,2,3-dithiazolium salts (Section 4.11.8.5) has been extended to hetarylamines (Scheme 17). More importantly, a new impetus for its investigation and development was provided when benzo-l,2,3-dithiazolyl radicals were shown by Mayer and co-workers to be intermediates. The reaction in a modified form was transformed by the above authors to an effective method for synthesis of this new class of stable radicals. When applied to acyclic enaminoketones the thiosulfinylamine precursor of the free radical could be isolated (Scheme 18). It was also extended to cyclic and acyclic oximes to afford fused and monocyclic... 

A new wave of interest and productive research was aroused by synthesis of tricyclic condensed derivative benzobis(l,3,2-dithiazole) (BBDTA) which was shown experimentally to afford at least three distinct oxidation states dication, radical cation, and diradical <86SM233, 86SM239). This has been helpful for developing an approach to ferromagnetic organic metals in which homomolecular stacks are formed from donor-acceptor complexes in which the donor is a triplet and the acceptor a radical ion derived from the donor <86SM233>. Initial experiments showed conductivities lO " -10 S for complexes of BBDTA radicals with TCNQ <86SM239>. 

Dithiazole systems have received most attention in synthesis. 

In CHEC-II(1996) <1996CHEC-II(7)89> only one system, the thieno[2,3-rf -l,2,3-dithiazole, was covered in this section. Since then, there have been more examples of reactions of fully conjugated 5-5 fused heterocycles of the type being considered in this chapter. Although the number of examples of these systems has increased, most of the studies have been carried out on their synthesis rather than on their reactions. 

Opening of the dithiazole ring of the imidazolo[4,5-r7 [l,2,3]dithiazole 107 was employed as a key step in a multistep synthesis leading to hydroxamic acid derivatives 108 and 109 which are under investigation as matrix metalloproteinase inhibitors. Following initial reaction of 107 with NaOH treatment with 2-bromo-3-(4-chlorophenyl)propionic acid tert-butyl ester lead to the thioethers 108 from which 109 could be obtained (Scheme 10). <2000W0063197>. 

While studying the chemistry of 4,5-dichloro-l,2,3-dithiazolium chloride (Appel s salt) and its derivatives, Besson reported the synthesis of various benzothiazoles from N-arylimino-l,2,3-dithiazoles, which could be synthesised from commercially available aromatic amines28. In this work, the authors explored a variety of strategies to construct the benzothiazole ring and demonstrated that in all cases the focused microwave methodologies were more productive and under well-defined conditions provided convenient methods for scale-up (Scheme 3.17)28. Comparisons were also made between reactions performed under solvent-free conditions and in the presence of solvent29. It is noteworthy that there is no general rule and some reactions performed in the presence of solvent may sometimes be more convenient than the same dry media reaction. 

Frere, S., Thiery, V. and Besson T., Eco-friendly microwave-assisted scaleable synthesis of 2-cyanobenzo-thiazoles via N arylimino 1,2,3 dithiazoles, Synth. Commun., 2003, 33, 3789-3798. 

Kim et al. [103] have shown that spiro-(3-lactams 128 (Scheme 32) obtained by a facile synthesis, serves as a precursor for the synthesis of hitherto unknown (3-lactams undergoing cleavage of the bond between S-l and S-2 with nucleophiles. Treatment of 5-substitutedimino-4-chloro-5//- l, 2,3-dithiazoles 126 with 2-chloro-2-phenylacetyl chloride 127 in the presence of triethylamine afforded spiro-(3-lactams 128. 

Scheme 32 Synthesis of spiro-fl-lactams using 5-substitutedimino-4-chloro-5//-l,2,3-dithiazoles and 2-chloro-2-phenylacetyl chloride...

The reaction of 5-arylimino-l,2,3-dithiazoles 56 with hydroxylamine proceeds smoothly to give A -arylcyanoform-amidoximes 98 (Equation 19), which can be utilized as starting materials for the synthesis of 4-substituted-2-cyanoquinazolines and 4-aryl-3-cyano-l,2,4-oxadiazin-5(67/)-ones <1999H(51)2653>. 

Much attention was given in CHEC-II(1996) <1996CHEC-II(4)409> to the synthesis of 1,2,3-dithiazoles. Cyclic and acyclic oximes were found to be important precursors to their preparation. The discovery of 4,5-dichloro-1,2,3-dithiazolium chloride (Appel salt 20) from the reaction of commercial and cheap acetonitrile and disulfur dichloride gave strong impulse to the synthesis of various 1,2,3-dithiazole derivatives. Formation of the 1,2,3-oxathiazole ring involved almost exclusively the conversion of m -aminohydroxyl compounds to the A-oxide derivatives. 

Research in the reviewed period 1995-2005 has covered more the chemistry of 1,3,2-dithiazoles and less the chemistry of 1,3,2-dioxazoles. 1,3,2-Oxathiazoles and their derivatives were not investigated in this period. Much attention has been paid to the neutral 1,3,2-dithiazolyl radicals including their synthesis, theoretical and structural study, and application. Special attention was given to their magnetic properties and conductivity. 1,3,2-Benzodithiazole. Y-oxidcs were of interest as enantiomeric compounds and intermediates for the preparation of enantiopure amines and alcohols. 

Synthesis of 1,3,2-dithiazoles has been the most extensively studied. Various structural types of these compounds have been synthesized in 1990s from raV-dithiols, bis(sulfenylchlorides), and alkynes <1996CHEC-II(4)433>. Much attention has been paid to the preparation of stable 1,3,2-dithiazolyl radicals and, especially, cations. The synthetic potential of 1,3,2-oxathiazoles and 1,3,2-dioxazoles is restricted by several uncommon procedures including nitrosation of thiolcarboxylic acids and photochemical addition of nitrobenzene to alkenes <1996CHEC-II(4)433>. 

To study the stability of 5-methyl-1,2,4-dithiazole-3-one 27 in solution at room temperature, the sulfurization efficiency of the freshly prepared compound was compared with a 3-week solution in the synthesis of 25-mer oligodeoxyribonucleotide phosphorothioate <1999TL2095>. The result obtained showed that in both cases the same sulfur transfer efficiency (>99.5%) was achieved. 

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