Annelated Thiophenes

Gewald reaction in the synthesis of annelated thiophenes as biologically active substances 90PHA545. 

Mass spectrometry of annelated thiophenes 88MI19 90MI15. Peri-condensed thiophenes 90H(30)1219. 

Thieno-annelated tetracyanoquinodimethanes and dithiadiselenafulva-lenes as organic conductors 89PS(43)187. 

---

Potts and co-workers have used phosphorus pentasulfide and pyridine as a standard reagent for constructing annelated diphenylthiophene rings from o-dibenzoyl compounds. Many of these annelated thiophenes can be written only in the tetracovalent sulfur or ylid dipolar form (96) and are thus termed nonclassical 123 other examples, particularly of the synthesis of non-classical thienoisothiazoles, have been reported by Gotthardt.124... 

The electron-rich thiophene ring system can be annelated by intramolecular Friedel-Crafts acylation reactions to give fused thiophenes <99IJC648, 99JMC2774>. The synthesis of a thiophene isostere of ninhydrin involved an intramolecular Friedel-Crafts acylation <99SL1450>. Specifically, treatment of thiophene 86 with thionyl chloride followed by aluminum chloride gave annelated thiophene 87. The synthesis of isothianinhydrin 88 was then accomplished in six steps from 87. 

These methods are limited in scope. Direct thiation has been reported for the transformation of vicinal diketones to [3,4]-annelated thiophenes <1996CHEC-II(7)49>. Thionations and selenations of vicinal halomethyl ketones with thioacetamide or iV,iV-diethylselenopropionamide as sulfur and selenium donors, respectively, have also been reported <1996CHEC-II(7)49>. In a recent example, thieno[3,4-f]pyrazoles 160 were readily prepared from aryl 5-bromomethyl-l//-l-phenylpyrazole-4-yl ketones 159 by reaction with thioacetamide (Equation 35) <1998JHC71>. Additionally, an example of an amination cyclization by reaction of 161 with benzylamine to afford pyrrolo[3,4-i/ thiazole 162 has been described (Equation 36) <1998JHC71>. 

Polarimetry, circular dichroism (CD) and optical rotatory dispersion (ORD) are the most important tools for the study of properties arising from optical activity. Although many chiral thiophenes have been prepared, there is no secure basis for a systematic discussion of the special effects of thiophene or annelated thiophene rings. For the purpose now at hand it is more expedient to discuss three different areas in which thiophene containing molecules and the related chiroptical techniques are central features. 

The parent nonclassical annelated thiophenes represented by structure (Id X = S, Y = O, NR, S, Se) are unknown however, there is considerable information on their characteristic reactions, mainly as ylides in the case of those derivatives which have been either generated in solution or isolated as stable solid compounds. 

The known nonclassical A,B-diheteropentalenes consist of compounds containing an annelated thiophene or selenophene ring, the only uncharged nonradical representations of which contain a tetravalent sulfur or selenium, while the charged structures represent carbonyl, azomethine, thiocarbonyl or selenocarbonyl ylides. The parent systems have not yet been synthesized, only substituted compounds being known. The properties of these substituted derivatives provide a good measure of understanding of the reactivities of the parent systems. 

It seems likely that aromatic amines which are found in liquefaction products have been produced by a combination of thermolysis and hydrogenation. There is no evidence for aromatic amines in coals from either selective oxidation degradations (22) or from direct X-ray Photoelectron Spectroscopy measurements (23). Oxidations would produce very stable nitroaromatics which are not seen. Another possible structure for this formula is phenoxazine(Vb). Such a molecule would not survive high temperature combined with long reaction times. Although annelated thiophene with a pyrrole(VI) would appear to be a likely structure in coal, there is no evidence for its existence in any of the coal derived materials. 

Fig. 15.14 Carbon-sulfur (C2S)H helix illustrated as stick and space-filling plots for oligomers of 21 helically annelated thiophenes.

The annelated thiophene 35 was synthesized in 91% yield as shown in Equation (8). In cyclic voltammetry, it showed a well-defined reversible oxidation wave in contrast to the irreversible oxidation waves obtained for thiophene analogs having only alkyl substituents at all four positions. 

Intramolecular addition of thiolate, dithiocarboxylate, and enedithiolate sulfurs to unsaturated carbon-carbon bonds also provides a convenient way to thiophenes. Thus, reductive cleavage of the thioester group of the compound (11) followed by intramolecular addition of the thiolate sulfur to the triple bond affords the thiophene (12) directly (Equation (2)) <93SL209>. In this way, a number of alkyl-substituted and six-membered ring annelated thiophenes were synthesized in good overall yields. 

Treatment of the ketenethioacetals (73) with BujSnH under radical forming conditions (AIBN, PhH, reflux) directly affords thiophenes (79) and/or (80) (Scheme 21) <93TL5653>. The reaction involves a radical centered tandem cyclization-fragmentation sequence for example, cyclization (74)- (75), fragmentation (75)- (76), cyclization (76)- (77), fragmentation (77)- (79). Application of this procedure to some other annelated thiophenes was also described. 

U.v.-Photoelectron spectra are available for (49)—(52) and diben-zothiophen (55). On the basis of band shapes and PPP calculations, the first three bands have been assigned to -ionization potentials. The good agreement obtained between measured and calculated ionization potentials suggests that sulphur 3d participation must be very small. In contrast, Johnstone et have explained the striking resemblance of the photoelectron spectra of the annelated thiophens to the iso-ir-electronic hydrocarbons naphthalene and anthracene, by the 3d participation of the sulphur atoms. This resemblance is well known, and although the usefulness of the PPP model without d-orbitals has been confirmed, e.g. by calculations of the spectral data of (49)—(53), " of (55) and annelated compounds, " ... 

---