Thieno thiophenes, structure

Horton,however, correctly observed that the product obtained by Friedmann could have the structure of thieno[3,2-6]thiophene (2) type rather than that of 1, since 2,5-dimethylthieno[3,2-6] iophene (18) can be formed by ring closure through sulfur bridging without carbon chain isomerization [Eq. (3)]. 

In 1949 Cox and co-workers ° from X-ray structural analysis and quantum-mechanical calculations suggested that thieno[3,2-b]thiophene (2) possesses a ground state intermediate form between the extremes with completely localized double bonds and that with complete delocalization of TT-electrons. The discrepancy between the theoretical and experimental (Fig. 1) values (0.05 A) for the central C,—Cg bond was noted, and the thienothiophene (2) molecule was shown to be planar and to have a center of symmetry. 

Recent X-ray structural studies of selenopheno[3,2-b]selenophene (12) have shown it to be isostructural with thieno[3,2-b]thiophene (2). The C—C bond lengths in these molecules are nearly the same (Fig. 2). 

Thieno[3,4-6]thiophene (3) possesses three plausible sites of attack, positions 2,4, and 6. However, consideration of resonance structures in-dcates that electrophilic substitution should occur at positions 4 or 6 rather than at 2. 

Bugge brominated thienothiophenes 1 and 2 with IV-bromo-succinimide in glacial acetic acid to 2-bromothieno[2,3-6]thiophene (66%) and 2-bromothieno[3,2-6]thiophene (55%). The structure of 2-bromothieno[2,3-6]thiophene was confirmed by the replacement of bromine by lithium at —70° followed by carbonation to thieno[2,3-6j-thiophene-2-carboxylic acid 2-bromothieno[3,2-fe]thiophene was independently prepared by the treatment of 2-lithiothieno[3,2-6]thiophene with one equivient of bromine at —70°. The 2-bromo derivatives of thienothiophenes 1 and 2 decompose within several hours at 20°, but remain uncWged for weeks at —15°. 

A reactivity study of the isomeric 2-vinylthieno[3,2-/ ][l]henzofuran 95 as well as of the structurally related 2-vinyl[l]thieno[3,2-/ ][l]benzothiophene 96 and 2-vinylthieno[3,2- ]thiophene 97 with dienophiles was performed by Svoboda and co-workers <2004TL2189>. Cycloaddition reactions were performed by heating 95-97 with dimethyl acetylenedicarboxylate (DMAD) to reflux in toluene under a nitrogen atmosphere. 

The structure of the benzoate derivative 166 was established by X-ray analysis, confirming the selective oxidation of the sulfur atom at the 6-position of thieno[2,3- ]thiophene-2-sulfonamides. The activated double bond of the cyclic vinyl sulfone moiety readily underwent nucleophilic addition, which was exemplified by reaction of 165 with 4-methoxybenzylthiol in the presence of base to provide a mixture of 167 and 168 <1999JHC249>. 

Over the last few decades there has been much interest in the thiophene-based systems and considerable effort has been expended in many laboratories on various aspects of their chemistry, including synthesis, structural studies and theoretical calculations and predictions. X-Ray analysis of the crystal structures of thieno[3,2-6]thiophene (3) (49AX356), selenolo[3,2-6]selenophene (4) (69AX(B)1374) and thieno[3,2-6 jfuran derivative (5) (79CC366) have been reported. 

Theoretical calculations using the semiempirical CNDO/2 method including d- orbital participation in (Id X = O, NH, S Y = S) predicted singlet ground states for these systems as well as substantial n- bond character between the S—C bonds arising from dir-pTr overlap, and very little double bond character in the central C—C bond (74JA1817). There is also considerable contribution to the electronic structure from dipolar canonical forms in (Id X = O, NH Y = S) compared to thieno[3,4-c]thiophene (9) as evidenced by the respective calculated dipole moments of 0.15 and 3.21 D for the former and 0.00 D for the latter. 

A perusal of the / values in Table 1 also shows that/aa is higher in the [3,2-6]-annelated systems than in the corresponding [2,3-6] isomers. For example / , in thieno[3,2-6]thiophene (3) and N-benzylthieno[3,2-6]pyrrole (18) is 1.55 and 1.3 Hz compared to 1.17 and 1.0 Hz for the corresponding [2,3-6 ]- annelated systems (7) and (19). This relatively high value for / - in the [3,2-6]-fused systems is a consequence of the transmission of the spin interactions between the protons through the v- framework rather than the cr-framework. In qualitative terms this means that several resonance structures can be written for such systems wherein electronic perturbations at C-2 are effectively transmitted to C-5 rather than C-6 (Scheme 4). 

Thieno[3,4-c]thiophenes 6 have attracted much attention from both theoretical and spectroscopic viewpoints as 10-7t-electron heterocycles with nonclassical structures [1-3]. However, the synthesis of thieno[3,4-c]thiophenes is not easy. This chapter surveys known compounds of this type and their methods of synthesis. 

The majority of methods for the synthesis of thieno[2,3-c]pyridines and related fused structures can be tentatively divided into two groups based on the construction of the pyridine or thiophene rings, respectively. 

An x-ray crystallographic analysis of bcnzo[J,2,3- / 4,5,6-cV ]bis(thieno)[2,3-c]thiophene (61) demonstrated that the molecule is planar and symmetrical but has strained bond angles. The crystal structure comprises herring-bone type column stacking with intercolumnar heteroatom interactions. Compound (61) showed the same oxidation potential as perilene and, like perilene, formed an iodine complex with the relatively high electroconductivity of 0.11 S cm-1 <93BCJ2033>. 

The electron-withdrawing effect of the isothiazole unit is evident in the proton chemical shifts of H-3 and H-4 in 5-phenylfuro[3,2-d]isothiazole (15), V-methyl-5-phenylpyrrolo[3,2-parent monocyclic heterocycles <80BSB773,85KGS223). As expected, changing the orientation of the isothiazole subunit (i.e., thieno[2,3-c]isothiazole (17)) vis-a-vis the thiophene subunit has little effect on the chemical shift of H-4 (see structures (14a) and (17)) <82AJC385>. 

Unequivocal structural proof of l,l,4,4-tetramethyl-l//,4//-thieno[3,4-c]thiophene (see Scheme 19) was obtained by X-ray crystallographic analysis (80TL3617). Methyl iV-vinyl carbamate adds benzonitrile oxide to yield a mono- or bis-adduct, depending upon the experimental conditions. The syn stereochemistry of the bis-adduct (10) has been elucidated by an X-ray structure determination which showed that the carbamate moiety orients its NH above the isoxazolidine ring and toward the oxygen of the syn-oxadiazolinic ring (NH------O is 3.08 A) <80JCR(S)4341>. 

Crystal structures for a number of bimanes (see Scheme 6) have been reported (81JOC1666). The formation from 3-(l-pyrrolidinyl)thiophenes and dimethyl acetylenedicar-boxylate (DMAD) of 6,7,7a,8-tetrahydro-5IT-thieno[2,3-6]pyrrolizines (226) always occurs stereospecifically, as shown by the X-ray structure of (226) (81JOC424). It is also shown that in l,3a,6,6a-tetrahydropyrrolo[3,4-c]pyrazoles (see equation 70), both of the cw-fused five-membered rings are in the envelope form with six peripheral side groups directly bonded to them (81BCJ41). 

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