2- Methyl-2,3-dihydrothieno -thiophene

Additional studies featuring reactions of thiophene derivatives detail biohydrolysis of (S)-3-(thiophen-2-ylthio)butanenitrile <06TL8119>, lipase catalyzed resolution of thiotetronic acids <06TL7163>, enzymatic kinetic resolution of l,l-dioxo-2,3-dihydrothiophen-3-ol <06TL5273>, and efficient synthesis of 6-methyl-2,3-dihydrothieno[2,3-c]furan 55, a coffee... 

Dipolar cycloaddition of 2,4-(trimethylsilyl)- and 2,4-(trimethylgermyl)-substituted thiophene-1,1-dioxides as well as silylated 2,2 -bithiophene-1,1-dioxides was investigated. It was shown that only the C(4)=C(5) double bond of 2,4-disubstituted thiophene-1,1-dioxides interacts with acetonitrile oxide to give thienoisoxazoline dioxides. Bithiophene derivatives were inactive or their reaction with nitrile oxide was accompanied by desilylation. Cycloaddition of benzonitrile oxide with all mentioned sulfones did not occur. The molecular structure of 3a-methyl-5.6a-bis(trimethylgermyl)-3a,6a-dihydrothieno 2.3-c/ isoxazole 4,4-dioxide was established by X-ray diffraction (263). ... 

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. ... 

Rearrangement of allyl 3-thienyl sulfide (45) gives 2-methyl-2,3-dihydrothieno[3,2- >]thiophene (46) [Eq. (21)]. 

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). 

Analogous oxidation of methyl 4,6-dihydrothieno[3,4-i]thiophene-2-carboxylate (134) leads to the 5,5-dioxide (135) (70%) hydrolysis and subsequent oxidation with sodium metaperiodate at 0° (cf. Leonard and Johnson ) results in 2-carboxy-4,6-dihydrothieno[3,4-i]thiophene-5-oxide (91) (74%). ... 

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 ... 

As in the synthesis of thieno[2,3-,7]-l,2,3-thiadiazoles, thieno[3,2-.7 -l,2,3-thiadiazoles are made using diazotization of aminothio-substituted thiophenes and by Hurd-Mori reaction of hydrazones. Diazotization of compound 134 with NaN02 in AcOH/HCl at 0°C produced methyl thieno[3,2- / -l,2,3-thiadiazole-5-carboxylate 135 but in only low yield. Hydrazone tautomer 136 treated with excess SOCI2 in CH2CI2 at room temperature gave dimethyl thieno[3,2- / -l,2,3-thiadiazole-5,6-dicarboxylate 137 and dimethyl 5,6-dihydrothieno[3,2- / -l,2,3-thiadiazole-5,6-dicarboxylate 138 in a ratio of 3 2 (Equations 20 and 21) <1998H(48)259>. 

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 complex sequence of pericyclic reactions, intramolecular and intermolecular cycloadditions and cycloreversions, was studied in an attempt to readily achieve bicyclic five-membered heterocycles, the methyl 4,6-dihydrothieno- and methyl-4, 6-dihydrofuro[3,4-b]-furan-3-carboxylates 146 and 147. The results give further evidence of the potential of intramolecular Diels-Alder based multiple processes [129], 2-Substituted furans and thiophenes 148 and 149, heated in the presence of 3,6-di(pyridin-2 -yl)-,y-tetrazine, underwent intramolecular and intermolecular cycloadditions. The cycloadducts underwent double cycloreversion reactions with the loss of a nitrogen and dipyridyldiazine as illustrated in Scheme 2.55. The electron-deficient dipyridyltetrazine reacts with the isolated, electron-rich olefinic bond rather than with the bond conjugated with the methylcarboxylate. 

Thiophen Analogues of Isoquinoline. - Several derivatives of thienol3,2-c]pyridine, such as 4-allyl-5-methyl-4,5-dihydrothieno-... 

Ionic hydrogenation of 2-methyl-2,3-dihydrothieno[2,3-Z)]-thiophene (262) affords cw-2,8-dithiabicyclo[3.3.0]octane (263) (79MI1). 

---