From dithiazoles

From dithiazoles. The alkylation of phenylthiuret (45) is attended by isomerization to 1,2,4-thiadiazole derivatives. Thus methylation or benzylation in alkaline media gives 5-imino-3-alkylthio-2-phenyl-l,2,4-thiadiazolines (46 R = Me or PhCHg, R = Ph, R = H), which can be independently synthesized by the oxidation of 2-5-alkyliso-l-phenyldithiobiuret (47 R = Me or PhCHg, R = Ph, R = H). Conversely, the dealkylation, by concentrated hydrochloric acid, of 3-t-butylthio-5-phenylimino-l,2,4-thiadiazoline (46 R = Bu R = H, R = Ph), obtained from (47 R = Bu , R = H, R = Ph), proceeds with the opposite isomerization, yielding (45) instead of the expected (46 R = R = H, R = Ph). Possible mechanisms of these reactions, and their significance for the structure of phenylthiuret, have been discussed. However, the issue is complicated by the fact that different alkyl halides produce different structural types of the 1,2,4-thiadiazole system.  

The thermal decomposition of 5-(dialkylamino)-3-alkylimino-l,2,4-dithiazoles (48) gives products derived from 2 molecules of the reactant, with loss of one atom of sulphur. They are formulated as the substituted 3,5-bis(thioureido)-l,2,4-thiadiazolidines (49) and are thought to arise by a mechanism involving intermediate spiranes. The 3-phenylimino-analogues of (48) decompose differently, yielding benzothiazole derivatives. The same class of 1,2,4-thiadiazolines (49) arise also by the successive alkylation and aminolysis of the 1,2,4-dithiazoles (50).  

Nagano, M. Oshige, T. Matsui, J. Tobitsuka, and K. Oyamada, Chem. and Pharm. Bull. 

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Iminodithiazoles 108 prepared from Appel salt 20 and o-aminobenzyl- and o-aminophenethyl-alcohols can be converted into 3,1-benzoxazine 109a and 3,1-benzoxazepine 109b by treatment with sodium hydride in THF (Equation 22) <1997SL704>. The oxygen-containing heterocycles 109 are apparently formed by cyclization of the alkoxide from dithiazole 108 onto the imine bond, followed by loss of S2 with generation of the cyano group. 

A new method was developed for the formation of A -(2-aroylbenzofuran-3-yl)-2-hydroxythiobenzamides from dithiazole and bromoacetylaryl derivatives <05H(65)1295>. 

Li and co-workers introduced a rapid and efficient microwave-assisted method to prepare new disubstituted 1,3,4-thiazoles from 1,4-disubtituted thiosemicarbazides with the objective to obtain biologically active molecules. The intermediate l-aryloxyacetyl-4-(4-methoxybenzoyl)thiosemicarbazide was irradiated in an excess of glacial acetic acid in a domestic microwave oven and led to the formation of 2-(methoxybenzoyl-5-aryloxymethyl)-l,3,4-dithiazoles in good yields [30] (Scheme 20). 

Transformation of the thiadiazolopyrimidine compound 138 to the fused dithiazole 140 also follows a fairly complicated pathway <2004JHC99>. When the derivative 138 is treated with carbon disulfide, a cyclization reminiscent of 1,3-dipolar cyclization takes place with the reagent acting as a dipolarophile to give a />OT-fused tricyclic intermediate containing a hypervalent sulfur atom 139. This intermediate can undergo isothiocyanate elimination to furnish 140. It is interesting to note that the sulfur atom of the thione moiety in the product is derived from carbon disulfide. 

Heterocycles with two sulfur atoms obtained from sulfur monochloiide, for example, 1,2-dithioles, 1,2,3-dithiazoles and 1,2-dithiines, are the most anticipated compounds because they are obtained by a direct insertion of two sulfur atoms during heterocyclic molecule construction. But even in that case some... 

A series of condensed 1,2,3-dithiazoles were prepared by Oakley and coworkers from o-aminoaromatic and heterocyclic thiols and S2CI2. This approach is more beneficial than a common Herz reaction that fails when applied to some aromatic amines, especially to phenylenediamines (1999JA969 Scheme 59). 

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). 

The single known N-oxide of 1,2,3-dithiazole 132 was isolated from cyclic oxime 133 and sulfur monochloride (1985TL189 Scheme 66). 

H-l,2,3-Benzodithiazol-6-ones 141 were prepared from p-benzoquinone-4-oximes, S2CI2, N-ethyldi/sopropylamine and NCS (1998T223 Scheme 72). Some ring chlorination occurred and 2,6-substituents were retained in the products except for the ferf-butyl group, which was replaced by chlorine. 1,4-Naphthoquinone 4-oxime and 1,2-naphthoquinone 2-oxime similarly gave dithiazole derivatives 142 and 143 (1998T223). 

Novel routes to 1,2,3-dithiazole ring systems from polysulfurdi- and triazepines discovered by Rees and co-workers involve their reactions with acetylenes to give (134) and (135) and the thermolysis of (132). 

A hypsochromic shift was observed for the benzo-bis-l,3,2-dithiazole system (Section 4.12.4.6) with increasing oxidation state from diradical (62) through radical cation (61) to dication (60) 560, 504, and 450 nm <86SM239>. 

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>. 

Reaction of 5-phenyl-3//-l,2,4-dithiazole-3-thione (84) with 1,2-diphenylcyclopropenone leads to the SS bridged ring-opened cyclopropenone product (85) (70%) and the trithiaheterapentalene bicycle (25 R = Ph)(7%) which is believed to result from thermal decomposition of (84) (Equation... 

Thioxo-1,2,4-dithiazolidines can be obtained from thioxo-l,2,4-thiadiazolidines by Dimroth rearrangement (Scheme 47) or reversibly by addition and elimination of acetone (Scheme 22). 1,2,4-Dithiazole type products are also obtained from thiocarbonyl isothiocyanates (154) by reaction with CI2 <84CHEC-I(6)897>, PhMgBr, Sj, or CS2. Other routes include reactions of carbonyl isothiocyanates and thiocarbonyl isocyanates with P4S10 or Sg <84Chec-I(6)897> and sulfonyl isocyanates with dialkyl thioketenes. Phenylisothiocyanate heated with N,C-disubstituted oxaziridines affords 3,5-diimino-l,2,4-dithiazolidines (226, 227). Other miscellaneous syntheses of 1,2,4-dithiazoline derivatives include cyclization of A7-thioacyl hexafluoroacetonimine to 5,5-bis(trifluoromethyl)-... 

Oxathiazoles and dithiazoles with exocyclic conjugation have also been obtained from appropriately substituted sulfenyl chlorides and carboxamides as detailed in Scheme 46. Part of the chlorocarbonylsulfenyl chloride chemistry has been reviewed <70AG(E)54>. 

Thermally labile 3-dialkylamino-5-dialkylthiocarbamoylimino-l,4,2-dithiazoles (263a) are obtained from 3-dialkylamino-1,2,4-dithiazole-5-thiones and dialkylcyanamides under high pressure (Scheme 52) <89CL1357>. 

Cyano-4-quinazolinones (4-oxo-3,4-dihydro-2-quinazolinecarbonitriles) 975 are available from 2-[A -(chloro-dithiazole)imino]benzoate esters 973 by reaction with primary aliphatic amines at room temperature <1998JHC659, 2002H(57)1471, 2002TL3993, 2005TL7477>. 

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>. 

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