Dithiins, aromaticity

Anti-aromatic 1,2-dithiins 179 display properties opposite to those of 1,4-dithiins 180, whose dications show aromatic stabilization. Unlike other antiaromatic compounds, the 1,2-dithiin derivatives, with eight jr-electrons (such as 181 and 182), appear in... 

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). 

Thermodynamic data has been published for 1,3- and 1,4- dithianes <99JCT635, 99JOC9328, 99T359>. Both theoretical and experimental evidence indicates that the 1,4-dithiin dication is aromatic <99CC777>. 

Formal replacement of one double bond in thiepin (51) by a sulfur atom leads to 1,2- (53) and 1,4-dithiin (54). The latter compound has been synthesized,70 and it is a non-planar, thermally stable molecule with a reactivity widely different from that of aromatic systems. A refined HMO method (Model B)71 has been used successfully to explain known properties of 54, and remarkably good agreement was obtained between the calculated and experimental C—S—C and C—C—S bond angles. For the parameters used (8S =0, pcc = 1.06, pcs = 0.77), the highest occupied orbital is anti-bonding, in agreement with the high... 

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). 

The identical vicinal coupling constants for 1,4-benzodioxin and 2,3-dihydro-l,4-dioxin, 3.73 Hz, have been cited as evidence to confirm the absence of aromatic character in the former (67AJC1773), and by the same reasoning (22) should also be non-aromatic (70ZC296). The corollary of this argument, however, is that the dissimilar 3/ values for 1,4-dithiin, 6.97 Hz, and its dihydro analogue, 10.02 Hz, indicate substantial aromatic character in the former. However, it has been pointed out that this simple type of comparison fails to allow... 

Chemical shifts of protons of 1,2-dithiin (Table 4) show no evidence of a ring current, but borderline aromaticity of a 1,2-oxathiin 2,2-dioxide derivative has been inferred from the chemical shift of H-6 which falls midway between that for a proton in a nonaromatic cyclic ether and for H-2 of furan (64JOC1110). 13C shifts of 1,2-oxathiin 2,2-dioxides at the C-4 and C-6 positions have been considered anomalous but may be rationalized by invoking mesomeric withdrawal of electron density from these positions by the SO2 moiety (770MR(10)208>. 

The early evaluations of DE (Section 2.26.2.1) for 1,4-dithiin and thianthrene, which suggested that both ring systems have aromatic character, received support from an empirical measurement of the resonance energy of thianthrene using combustion methods. The compound was found to have a resonance energy of 71 kJ mol-1 in excess of that for two benzene rings (55ACS847). However, it will be recalled that more recent theoretical treatments... 

Chemical two-electron oxidation of the corresponding 1,2-dithiin resulted in the formation of a stable solution of dication 95 (no decomposition was observed at 18°C for months)256 [Eq. (4.73)]. 1H and 13C NMR spectra of the dication exhibited resonances at considerably lower fields compared with those of the neutral starting material suggesting aromatic stabilization. Calculated geometries (B3LYP/6-31G ) indicate a planar ring and calculated chemical shifts are in fair agreement with observed values. The related 1,4-dithiin dication was also characterized.257... 

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