Thiophene thienothiophenes

The IR spectrum of thieno[2,3-6]thiophene (1) was first reported by Godart in 1937 in work devoted to the UV and IR spectral analysis of thiophene, thienothiophene 1, and benzo[6]thiophene. Comparison of spectral features in the 4000-11,000 cm" region of thiophene and benzene, thieno[2,3-6]thiophene (1) and naphthalene, and benzo[6]-thiophene, benzene, and naphthalene demonstrated, in Godart s opinion, the similarity of IR spectra (in this region) of thiophene, thienothiophene 1, and benzo[6]thiophene, on the one hand, and benzene, thienothiophene 1, and naphth ene, on the other hand. The molecular absorption coefficients of benzene and thiophene, as well as of naphthalene and thienothiophene 1, were also similar. 

Abstract The main methodologies for the synthesis of fused thiophenes (thienothiophenes, dithienothiophenes, and thienoacenes) and some of their oligomers and polymers are described. Such compounds are particularly important in materials chemistry. They have applications in organic light-emitting diodes (OLEDs), organic field effect transistors (OFETs), (dye-sensitized) solar cells, and electrochromic devices (ECDs). 

The bromination behavior of isomeric thienothiophenes (53-55) has been studied in detail. Both the [2,3-b] (53) and the [3,2-h](54) isomers reacted with one equivalent of NBS in acetic acid to give an a-monobrominated product, with some evidence of 2,5-dibromo species also being formed. With 2 mol of NBS these latter products were formed in good yield three molar equivalents led to 2,3,5-tribromothieno-[2,3-h]-and -[3,2-6]-thiophenes (Scheme 28). The monobromo compounds can also be prepared from lithium derivatives quenched with bromine [76AHC( 19) 123]. Apparently the [2,3-c]isomer (55) also reacted initially in the 2-position. 

An alternative approach to thienothienopyridines involves intramolecular electrophilic attack at C-3 of the thiophene ring. In this way, the thienothiophene 82 can be cyclized to the benzothieno[2,3-/]thieno[2,3-c]pyridine 83 upon treatment with polyphosphoric acid (PPA) at 150°C (Equation 3). Similarly, treatment of the amide 84 with POCI3 gives the corresponding 1-alkyl-3,4-dihydro-benzothieno[3,2-g]thieno[3,2-f]pyridine 85 <1999PS(153)401> (Equation 4). 

Several useful specialized reviews have appeared during the reporting period of this chapter. The chemistry of thienothiophenes <06AHC(90)125> and thienopyrimidines <06AHC(92)83> has been discussed in detail, whereas accounts of related interest highlight the field of thiaheterohelicenes <06OBC2518> as well as similar fused thiophene systems <06AG(E)8092>. 

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). 

All isomeric thienothiophenes are now known thieno[2,3-b]thiophene (1), thieno[3,2-b]thiophene (2), thieno[3,4-b]thiophene (3), and thieno-[3,4-clthiophene (4) (the last as a tetraphenyl-substituted derivative... 

According to the available literature, two main routes to the synthesis of isomeric thienothiophenes have been studied cyclization of various aliphatic substances, and cyclization of derivatives of the thiophene series. 

A synthetic route developed by Capelle and deConinck in 1908 produced thienothiophene 1 in somewhat better yields. By passing acetylene through the vapors of boiling sulfur and then trapi g the reaction products by carbon disulfide, they isolated, together with benzo[bl-thiophene, a compound, b.p. 225°, which formed a picrate similar to that obtained by Biedermann and Jacobson. ... 

Meyer et a/. obtained in low yields thiophene, 2-methylthiophene, benzo[6]thiophene, traces of thienothiophene 1, and some other products on passing a mixture of acetylene, hydrogen (or methane), and hydrogen sulfide at 640°-670° through a tube filled wth FeSj. 

Later authors established the approximate composition of products formed in the reaction of acetylene with sulfur at different temperatures. At 325° the composition was found to be CSj 77%, thiophene 9%, thienothiophene 1 6% at 500°, CSj 77%, thiophene 12%, and thienothiophene 1 6% at 650° CS2 83%, thiophene 5%, and thienothiophene 1 3%, with sulfur conversion being 38%, 74%, and 77%, respectively. When studying this reaction at 290°-390°, Bhatt et isolated thiophenol in addition to the above compounds but failed to increase the yield of thienothiophene 1. 

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. ... 

When studying the carcinogenic activity of polycyclic hydrocarbons and their antdogs containing thiophene rings (cf. Tilak "), Tilak et al synthesized both thienothiophene 1 and its isomer 2 in low yield from 2-thienyl dimethoxyethyl sulfide (23) and 3-thienyl diethoxyethyl sulfide (24), respectively, by the method developed for synthesis of thiophenes and thiopyrans - [Eqs. (10) and (11)]. The compounds 23 and 24 were prepared from 2- and 3-mercaptothiophenes. ... 

Another method for e preparation of aryl w-dimethoxyethyl sulfides was described by Pandya and Tilak. The procedure consists in allowing aryl lithium derivatives to react with 2,2,2, 2 -tetramethoxy-diethyl disulfide. Subsequent cyclization of the sulfides by polyphos-phoric acid yields 2-35% of condensed thiophenes and thiopyrans. By this method, thienothiophene 1 was prepared from 2-thienyllithium [Eq. (12)] and the previously unknown dithieno[2,3-6 3, 2 -i/]thiophene (5) was obtained from thienyl-2,5-dilithium. The possibility of synthesizing a heterocyclic analog (25) of pentacene from dithieno[2,3-6 3 2 -[Pg.130]

The mechanism of formation of two isomeric thienothiophenes by cyclization of 2-acetonylthio-thiophenes in the presence of aluminum chloride may be as shown in Scheme 1. 

Isomerization does not occur when the acetonylthio group is in the thiophene /J-position. Thus, 3-acetonylthio-thiophene with aluminum chloride in benzene results only in alkyl-substituted thieno[3,2-h]-thiophene (2) as shown by UV spectroscopy and the identity of acetyl derivatives of the cyclization products with those of well established alkyl-substituted thienothiophene 2 [Eq. (15)]. 

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 )... 

Syntheses of unsubstituted thieno[3,2-A]thiophene (2) and 3-methyl-thieno[3,2-6]thiophene were carried out in a similar way metalation of 3-bromothiophene with n-butyllithium at —70° and subsequent treatment with sulfur and methyl monochloroacetate gave methyl (3-thienyl-thio)acetate (60). Further reactions along the lines indicated above led to the thienothiophenes 2 and 27. 

Ortho-bi functional thiophenes provide the most convenient route to unsubstituted thieno[2,3-6]thiophene (1). 3-Bromothiophene yielded 3-thiophenealdehyde. The corresponding diethyl acetal, using the procedure for thienothiophene 2, led to thieno[2,3-6]thiophene (l) in about 40% yield based on 3-bromothiophene [Eq. (24)]. This method was also used by Gronowitz and Persson for the synthesis of thienothiophene 1. 

Introducing a second acyl group into monoacyl derivatives of the thiophene series by blocking the ketone group with excess aluminum chloride opened another route to substituted thienothiophene 1. ... 

As Stated above, one of the routes to thienothiophene 2 is cyclization of (3-thienylthio)acetic acid in the presence of concentrated sulfuric acid followed by action of the 2,3-dihydrothieno[3,2-2>]thiophen-3-one (22, R = H) formed with lithium aluminum hydride.Attempts by the present authors as well as those of Gronowitz and Moses to obtain... 

Unsubstituted thieno[3,4-6]thiophene (3) (see Litvinov and Fraenkel ), was prepared by Cava and Pollack s method for benzo[c]-thiophene i.e., thermal decomposition of H, 3 -benzo[c]thiophene sulfoxide. By refluxing 4/f,6/f-thieno[3,4-ft]thiophene-2-carboxylic acid 5-oxide (91) with acetic anhydride (the synthesis of dihydrothieno-thiophenes will be described below), Wynberg et a/." obtained the mixed anhydride 92 in 95% yield. Hydrolysis gave thieno[3,4-6]-thiophene-2-carboxylic acid (93) (88%). Decarboxylation of the acid (93) gave thienothiophene 3, unstable at room temperature [Eq. (29)]. 

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). ... 

Dihydrothieno[3,4-Z ]thiophene (131) was prepared by two methods. In the first (Scheme 8), chloromethylation of methyl thiophene-2-carboxylate (132) forms methyl 2,3-bischloromethyl-thiophene-5-carboxylate (133) (85%) cyclization of 133 with sodium sulfide in methanol yields (66%) methyl 4,6-dihydrothieno[3,4-i]-thiophene-2-carboxylate (134). Peroxide oxidation of 134 gives 2-methoxycarbonyl-4,6-dihydrothieno[3,4-h]thiophene 5,5-dioxide (135) and hydrolysis of 134 followed by metaperiodate oxidation furnishes the sulfoxide (91). Thienothiophene (131) was produced by hydrolysis and decarboxylation of 134. As indicated above, the sulfoxide (91) was used for the synthesis of thieno[3,4-6]thiophene (3). 

In the second route to thienothiophene (131) [Eq. (41)], 3-thiophene-aldehyde ethyleneacetal (136) was converted into diiophene-2,3-dialdehyde (138), which was reduced to 2,3-bishydroxymethyl-thiophene (139). 139 was converted by PBrj into 2,3-bisbromomethyl-thiophene (140), which with anhydrous sodium sulfide in DMF formed thienothiophene (131) (27%). 

In 1967 Cava and Pollack obtained derivatives of the fourth, so-called nonclassical , thienothiophene— thieno[3,4-c]thiophene (4), a condensed heterocycle with formdly tetracovalent sulfur (42)j. The reaction of 3,4-bischloromethyl-2,5-dimethylthiophene (141) with sodium sulfide afforded 4,6-dimethyl-lif,3ff-thieno[3,4-c]thiophene (142) periodate oxidation of 142 gave die corresponding sulfoxide (143) in 91% yield. Attempts to convert the sulfoxide (143) into the thieno-[3,4-c]thiophene by the method used for S3mthesizing benzo[c]-thiophene led only to polymer. However, 24% of adduct 144 and 10% of 145 were obtained by refluxing sulfoxide (143) with N-phenylmaleimide in acetic anhydride, indicating that the thieno[3,4-c]-thiophene was formed as an intermediate. 

In 1973 Cava et al. reported the synthesis of 4,6-dimethyl-l/f,3if-thieno[3,4-c]thiophene (142) and l,3,4,6-tetraphenylthieno[3,4-cl-thiophene (149) ° as well as data on some chemicaJ conversions of the latter and the dehydration of 4,6-dimethoxycarbonyl-l/f,3H-thieno-[3,4-c]thiophene sulfoxide. Thienothiophene (149) was also obtained (42%) by Potts and McKeough by condensation of anhydro-4-hydroxy-2,3,5-triphenylthiazolium hydroxide with dibenzoylacetylene followed by reaction of the product with P S,. 

Finally, in this section of syntheses from thiophenes, a catalytic one-step meftod for the preparation of thieno[3,2-2>]thiophene (2) should be mentioned. Reaction of 2-ethylthiophene with SOj over CrjOj/AljOj at 450° afforded a 13% yield of thienothiophene 2, together with thiophene, 2-methylthiophene, 2-vinylthiophene, and 2-aceto-thienone [Eq. (45)]. Under these conditions formation of the isomeric thieno[2,3-6]thiophene (1) was not observed. 

Wynberg and Bantjes studied the pyrolysis of thiophene at 800°-850° by mass spectrometry they established the presence of isomeric dithienyls, benzo[6]thiophene, and traces of naphthalene, isomeric phenylthiophenes, and thienothiophenes, besides unreacted thiophene and carbon disulfide. 

In a study of the formation and reactions of arynes at high temperatures. Fields and Meyerson plyrolyzed a thiophene solution of phthalic anhydride at 690° by mass spectrometry and gas chromatography they found benzene, naphthalene, benzo[b]thiophene, phenylthiophenes, bithienyls, thienothiophene 1, and naphthothiophene in the pyrolysis products. Pyrolysis of thiophene itself produced benzo-[Z lthiophene, thienothiophene 1, phenylthiophene, and bithienyl. The... 

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. 

Pig. 3. Bond lengths (A) and angles of the thienothiophene fragment of the 1,3,4,6-tetraphenylthieno[3,4-c]thiophene molecule. 

Recent analysis of the bond length data in thienothiophene isomers indicates good agreement for thieno[2,3-ft]thiophene (1) and thieno[3,2-6]-thiophene (2). However, while the S,—Cj distance in thienothiophene 1 coincides exactly with S,—C, distance, the calculated Sj—Cj distance in thienothiophene 2 is somewhat shorter than Sj—C,. In thieno[3,4-A]-thiophene (3) these bonds are a little longer than in thienothiophenes 1 and 2. The central C,—Cg bond in two condensed rings in thieno[3,4-i]-thiophene (3) and thieno[3,4-c]thiophene (4) is somewhat longer than the corresponding bond in the other two isomers 1 and 2. 

PMR spectroscopy has found wide application in studies of unsubstituted tWenothiophenes, " enophenothiophenes (Table I), > 9 carboxy-, formyl-, bromo-, and adkyl- thienothiophenes, and carboxy- selenopheno-thiophenes. The PMR meAod has also been used to study alkylthieno-[3,2-h]thiophene sulfones and 4,6-dihydrothieno[3,4-h]tMophene (131)9 analyze the mixture of products of the thio-Claisen ... 

In 2-substituted formyl thienothiophene 1 or 2 there is a slight long-range interaction (/cho-s Hz) between protons separated by seven bonds. With 3-formyl thienothiophene 1 or 2 no long-range coupling is observed between the proton of the formyl group and those of the thiophene system. A similar effect is also observed in 2-methyl-thieno[3,2-6]thiophene (35) and 3-methylthieno[3,2-b]thiophene (27). 

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