Heterocyclics 1.2- dithiins

Tricyclic dithiine derivatives of tetrathiafulvalene (TTF) 32 have been prepared for their increased electropolymerization potential <2000CC1005>. The effect of different tricyclic heterocycles upon the redox properties of TTF analogues was explored, and showed that the furan derivative 33 had an unusual nonplanar conformation that allowed for the attainment of higher oxidation states at relatively low oxidation potentials <2004JMC2822>. 

Other heterocyclic systems prepared by a thionyl chloride reaction include fused thiazoles,71 thiatriazoles,72 oxathiins,73 and dithiins 74 some further examples are given in reviews.53... 

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... 

Other heterocyclic compourtds containing four sulfur atoms - tetrathiocines 196, 197 - were synthesized from activated aromatic compounds, in particular 1,2-dialkoxybenzenes or 2,3-dialkoxynaphthalenes, and sulfur monochloride in acetic acid in fairly good yields (1989PS111 Scheme 97). Biphenyl 154 treated with S2CI2 under the same conditions yielded 1,2-dithiines (see Section 4.3). 

Simple side-chain reactions of 1,2-dithiin diols have been conducted. Besides the formation of esters, ethers (R = Me, Et, 7-Pr, cyclopropyl, Ph, pyridyl, cyclopentyl), and thioethers (R = H, TBDMS R = 4 -(4-hydroxyphenyl)-l//-tetrazole-5-thiol), selective oxidation of the primary alcohol groups in the presence of the 1,2-dithiin heterocycle could be readily achieved (Scheme 36) <1995JME2628, 1994SL201>. Additionally, amides, ureas, and carbamates of the dithiin diol were synthesized <1995JME2628>. 

There are few examples of the preparations of heterocyclic compounds containing two or more heteroatoms which involve cyclization with formation of a bond between two heteroatoms. The best known instances of this type of reaction, all of which are [6 + 0] reactions, are the preparations of benzocinnolines as outlined in equations (l)-(4). A similar type of approach to that outlined in equation (4) has been used for the direct preparation of the di-N-oxide (2) from the dioxime (1 equation 5). The naphthotriazine betaine (4) is obtained as one of the products of the thermal decomposition of the azidoazo compound (3 equation 6). 1,2-Dithiins and their dibenzo derivatives have been prepared by oxidation of appropriate dithiols and related starting materials as outlined in equation (7). All of these reactions are, however, somewhat specialized and there has been essentially no systematic study of the preparation of six-membered heterocycles via formation of a bond between two heteroatoms. 

Substitution products can be obtained from some 1,4-dithiins. Thus, 2,5-diphenyldithiin is formylated under Vilsmeier conditions, and mono- or di-nitrated and brominated in the heterocyclic ring. 1,4-Benzodithiin shows similar properties (see Scheme 51). 

In theory, an isosteric/isoelectronic aromatic ring replacement within a toxic or therapeutic molecule should lead to a retention of biological activity. The fact that this is sometimes not observed may mean either that the activity is heterocycle-specific or that unforseen changes in metabolism, biological distribution and excretion, partition coefficient or stability have accompanied the molecular change. In such cases, activity may be observed in in vitro assays while not being observed in vivo (cf. the possible case of the dithiin analogue of TCDD in Table 3). 

Several heterocyclic sulfur compounds have been shown to function as C2S sources in this type of thiophene synthesis. Thus 2,5-diphenyl- 1,4-dithiin 1,1-dioxide (255a) condenses... 

An authoritative review covering application of UV photoelectron spectroscopy to heterocycles appeared in 1974 <74PMH(6)l) and important work on saturated multi oxygen and sulfur compounds is discussed therein. However, the studies of 1,4-dioxin, its dibenzo analogue, 1,4-dithiin and phenoxathiin, which are referred to in the first part of this section, appeared after the publication of that review. 

Known compounds in this class include mainly 1,3-oxazine, 1,3-thiazine, 1,3-diazine (perimidine), and to a lesser extent 1,3-dithiine and 1,3-dioxine peri-annelated derivatives. The general strategy for constructing such systems is based on heterocyclization of 8-hydroxy-, 8-mercapto-, or 8-amino-substituted 1-naphthylamines 426 (X = NR)... 

Very recently a theoretical study of the tautomerism between 1,2-dithiins and dithiones was published139. Contrary to 1,2-dithiete, 1,2-dithiin (34a) is a nonplanar heterocycle with an energy barrier of inversion via the fully conjugated planar structure of 8.3 kcal mol 1, estimated attheMP2/6-31G(d) level. Similarly to what was found for 1,2-dithiete with respect to 1,2-dithioglyoxal, the cyclic unsubstituted 1,2-dithiin is predicted to be about 15 kcal mol 1 more stable than the open-chain dithiones (34b-34d). 

An investigation into the aroma of cooked small shrimp and krill revealed more than forty sulfur- and/or nitrogen-containing heterocyclic substances. Among these eight were newly identified as contributors to food flavor. The main ring structures encountered were pyrazine, trithiolane, dithiin and dithiazine. 

Few examples of photochemical transformations of the 10n heterocycles in this series have been reported. Notable is the conversion of thieno[2,3-c]isothiazoles (33) to thiophenes (37) by homolytic cleavage of the nitrogen-sulfur bond (Scheme 4). The enedithione (34) which arises from the initial diradical may undergo (a) cyclization via the bicyclic thiirane (35) or (b) electrocyclization to the 1,2-dithiine (36) <88H(27)2539>. Since similar rearrangements do not occur with isothiazoles, benzoisothiazoles, or the isomeric thieno[3,2-d]isothiazoles, this unique transformation is a direct consequence of the thieno[2,3-c]annelation. However, substituent effects on the efficiency of the transformation have not been explored. 

Carbosulfan carbamate, benzofuran Carboxin oxathiin, amide Cartap thiocarbamate CDAA see Allidochlor CJiinomethionat dithiin, heterocyclic nitrogen, quinoxaline... 

Dimethametryn heterocyclic nitrogen, triazine Dimethazone see Clomazone Dimethenamid heterocyclic sulfur, thiophene, amide Dimethipin heterocyclic sulfur, dithiin, sulfone Dimethirimol heterocyclic nitrogen, pyrimidine Dimethoate phosphoro organic, phosphoro dithioate, amide... 

Dithianon heterocyclic sulfur, dithiin, quinone Dithiopyr heterocyclic nitrogen, pyridine Diuron urea DNOC dinitrophenol... 

HETEROCYCLIC SULFUR COMPOUNDS DITHIINS, OXATHINS, THIOPHENES, THIOPYRANES, TRITHIANES... 

From sulfur- and nitrogen-containing five-membered heterocyclic compounds Photocyclization of l,3-dithiole-2-ones 723 affords thieno[3,2-r ]dithiins 725. The reaction probably involves cycliza-tion of the intermediate dithiones 724 (Scheme 110) <20010L3573, 2003JOC7115>. 

The mass spectra of several unsaturated sulfur heterocycles show the presence of 1,2-dithiete cation radicals. 1,2-Dithiete cation radicals also are obtained by treatment of a-hydroxyketones or a-diketones with sodium sulfide, sodium thiosulfate or sodium dithionite, and sulfuric acid. ° Bis(trifluoromethyl)-l,2-dithiete yields a cation radical directly when dissolved in sulfuric acid. ° The electron-spin resonance spectrum of the benzo-1,2-dithiete cation radical (formed in chlorina-tions with sulfur-containing reagents) has been observed.Thermolysis of a 1,4-dithiin may go via a l,2-dithiete. ° ... 

Gerson and co-workers ° have formed both cation- and anion-radicals from the heterocycle dithieno[3,4-6 3, 4 -e][l,4]dithiin-l,3,5,7-tetraone... 

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