Thienothiophenes reduction

Thiophene and thienothiophene units have been frequently used in thienoquinoid or condensed forms in the design of new molecular architecture (16). Incorporation of the thiophene or thienothiophene unit as a rc-bridge linker could stabilize the quinoidal structure in the reduced forms (Figures 13 and 14). These two-types of new dications (222+ and 232+) stabilize the presumed two-electron reduction state by contribution of the thienoquinoid substructures (22 and 23) instead of the quinoidal form in the dication 212+ (77). 

Challenger and Harrison found both thienothiophene 1 and its isomer 2 in the products of the reaction between acetylene and sulfur. To identify these compounds, Challenger et developed syntheses of unsubstituted and 2-alkyl-substituted thieno[3,2-f>]thiophene (2) from thiophene derivatives. Cyclization of (3-thienylthio)acetic acid in the presence of sulfuric acid gave 2,3-dihydrothieno[3,2-6]thiophen-3-one (22) (R = H) in 14% yield reducing the latter with lithium aluminum hydride resulted in thienothiophene (2) formation in 80% yield [Eq. (9)]. Similarly 2-methyl- and 2-ethyl-2,3-dihydrothieno[3,2-/>]thiophen-3-one were obtained from a-(3-thienylthio)propionic and a-(3-tWenylthio)-butyric acids in 30% and 27% yields, respectively their reduction yielded 2-methyl (32%) and 2-ethylthieno[3,2-6]thiophenes (52%). The parent acids were prepared from 3-mercaptothiophene. ... 

The synthesis of alkylated thieno[3,2-h]thiophenes (2) via a similar procedure was also studied. As stated above, existing methods for the preparation of a-alkyl-substituted thienothiophene 2 derivatives and thienothiophene 2 itself are inefficient. The reduction of 4-bromo-2-acetothienone (56) (prepared by bromination of 2-acetothienone )... 

Zwanenburg and Wynberg also proposed another route to the thienothiophene (112). 2,5-Dibromo-3,4-bisbromomethylthiophene (116) was cyclized with sodium sulfide to give 4,6-dibromo-l f,3/f-thieno[3,4-c]thiophene (117) in 60% yield 117 was then reduced to thienothiophene (112). l,3,7,9-Tetrabromo-4i/,67f,10.H, 12ff-dithieno-[3,4 C 3, 4 -/i][l,6]dithiecin (118) (18%) was also formed during the ring closure. Oxidation of thienothiophene (117) followed by reduction by zinc in acetic acid gave l/f,3H-thieno[3,4-c]thiophene 2,2-dioxide (119). ... 

The formation of a radical-anion with a very short lifetime on the surface of a sodium-potassium alloy during the reduction of thieno[3,2- ]-thiophene (2) at —100° was established by ESR (theoretical and experimental spectra are presented). The formation of the thieno[2,3-61-thiophene (1) radical-anion even under such extreme conditions was not observed. The difference in the stability of radical-anions of thienothiophenes 1 and 2 was accounted for by a greater degree of conjugation in thienothiophene 2 molecule as compared to 1. The spectrum of the thienothiophene 2 radical-anion distinctly exhibits two types of hydrogen atoms with coupling constants 4.87 and 0.52 Gauss. The... 

Aromatic substitution reactions are often complicated and multistep processes. A correlation, however, in many cases can be found between the charged attacking species and the electron density distribution in the molecule attacked during electrophilic and nucleoph c substitution. No such correlation is expected in radical substitution where the attacking particles are neutral, rather a correlation between the reactivities of separate bonds and a free valency index of the bond order. This allows the prediction of the most reactive bonds. Such an approach has been used by researchers who applied quantum calculations to estimate the reactivities of the isomeric thienothiophenes and to compare them with thiophene or naphthalene. " Until recently quantum methods for studying reactivities of aromatics and heteroaromatics were developed mainly in the r-electron approximation (see, for example, Streitwieser and Zahradnik ). The M orbitals of a sulfur atom were shown not to contribute substantially to calculations of dipole moments, polarographic reduction potentials, spin-density distribution, ... 

The structures of the acetylation products of 1 and 2 were also proved by the following conversions. The oximes derived from the acetyl thienothiophenes gave the corresponding acylamino compounds on Beckman rearrangement. The latter were identical with the derivatives obtained by reduction (Hj/Ni) in acetic anhydride of the 2-nitro-substituted thienothiophenes 1 and 2 [Eq. (61)]. 

Reduction by UAIH4 of 2,3-dihydrothieno[3,2-6]thiophen-3-one (22) and its 2-methyl- and 2-ethyl-derivatives afforded the appropriate thienothiophene Similarly, Gronowitz and co-workers ... 

Alkyl-substituted thienothiophenes can be prepared by reducing acetyl or formyl derivatives (see refs. 18,21,25,26,28,44,57,67,68). Wolff-Kishner reduction is preferred to the Clemmensen method, since the latter requires hot concentrated hydrochloric acid, which may cause resinification. ... 

Thienothiophenes, like thiophenes and benzo[h]thiophenes, easily undergo reductive desulfurization with Raney nickel. The method was fvst applied in this series by Challenger et to determine the structures of 2-acetylthieno[3,2-h]thiophene and 2-acetylthieno[2,3-hl-thiophene the former gave 2-octanone (229), and the latter 5-methyl-heptan-2-ol (230) [Eqs. (75) and (76)]. 

The reduction of thienothiophene 2 with Na-K alloy produced a radical-anion (see Section III,D), and a radical-cation resulted from oxidation with AlCl, in nitromethane or SbCl, in methylene chloride (see Section IV,B 5). No such conversion was observed in the case of thienothiophene 1 this is explained by the extended conjugation throughout the thienothiophene 2 molecide, impossible in thienothiophene 1. 

As already mentioned (Section III,D), reduction with sodium potassium alloy at —100° of thieno[3,2-6]thiophene (2) generates a short-lived radical-anion on the alloy surface.1 7,188,237 Sodium in alcohol opens one thiophene ring of thienothiophene (2) to give 2-ethyl-3-mercaptothiophene (227), which was characterized as its mercury derivative (228)18 [Eq. (74)]. 

Reduction by LiAlH4 of 2,3-dihydrothieno[3,2-6]thiophen-3-one (22) and its 2-methyl- and 2-ethyl-derivatives afforded the appropriate thienothiophene 2.21,25,28,29 Similarly, Gronowitz and co-workers48 used borohydride reduction of ketones 33 and 34 to prepare 2-methyl-thieno[3,2-6]thiophene (35). Attempts to reduce 2,3-dihydrothieno[3,2-6]thiophen-3-one (22)28 and 2,3-dihydro-4,6-dimethylthieno[3,4-6]-thiophen-3-one (87)T with zinc powder in acetic acid were unsuccessful. 

A new procedure was developed for the synthesis of benzoannulated thienothio-phene based on reduction of stilbene-2,2 -disulfochloride (131) with concentrated hydroiodic add in acetic acid (80ZOR425, 80ZOR430, 81MI2, 81USSR755785). This approach is applicable also to the synthesis of 2,7-disubstituted derivatives of thienothiophenes 121 starting from the corresponding 4,4 -disubstituted disulfo-nylchlorides. 

Tetrathiabenzo[l,3-cfirst time by dimerization of thieno[2,3- >]thiophene (142) (92PS73). More recently, it was found that catalytic reduction of 3,4-dibromothieno[2,3-i]thiophene (227) with an excess of activated zinc in the presence of bis(triphenyl-phosphine)nickel(II) chloride and tetraethylammonium iodide afforded only 4,4 -dibromo-3,3-bis(thieno[2,3- )]thiophene) (228) (in a maximum yield of 28%) (89AG1254). However, the reaction in the presence of a larger amount of the nickel catalyst afforded also dipenatlene 225. Optimization of the reaction conditions made it possible to increase the yield of the latter to only 14%. An alternative procedure was employed to transform thienothiophene 227 into trimethylstannyl derivative 229. The reaction of thienothiophene 227 with organotin intermediate 229 in the presence of the palladium triphenylphosphine complex afforded dipentalene 225 (13% yield). Derivatives 226 were prepared by lithiation of... 

Thienothiophens, Thienoselenophens, and Related Systems.—The thiophen derivative (738) cyclises to the thieno[2,3- >]tiiiophen (739)/ Electrochemical reduction of carbon disulphide in acetonitrile gives the di-anion (740), which forms the dithiolodithiole (741) on treatment with thiophosgene. The di(acylimino)tetrathiapentalenes (742) are obtained by the action of acid chlorides RCOCl on the complex of sodium cyanodithioformate with Perchloric acid transforms the bis-dithiocarbamate (743 R2N = piperidine) into the salt (744) the tetraselenium analogue has been prepared similarly/ ... 

Physical Properties.— Triethylsilyloxyl nitroxide radicals of thienothiophens and radical anions of three dithienothiophen 7,7-dioxides produced by potassium reduction in DME have been studied. ... 

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