2- Methyl-4 thieno

The influence of catalysts (A1C13 and SnCl4), acid chlorides, and solvents (dichloroethane, nitromethane) in the acylation of methyl 2-methyl-4//-thieno[3,2-b]pyrrole-5-carboxylate 48 was studied [17]. Conditions for the regioselective acylation processes were found and thus were obtained four types of compounds 49a-f, 50a-e and 51 (Fig. 6). 

Fig. 6 Methyl 2-me.thyl-4//-thicno 3,2-hlpyrrole-5-carboxylate 48, methyl 3-acetyl-2-methyl-4//-thieno 3,2-b pyrrole-5-carboxylate 49a, methyl 2-methyl-3-propanoyl-4//-thieno [3,2-h]pyrrole-5-carboxylate 49b, methyl 3-chloroacetyl-2-methyl-4//-thieno[3,2-h]pyrrole-5-carboxylate 49c, methyl 3-dichloroacetyl-2-methyl-4//-thieno[3,2-h]pyrrole-5-carboxylate 49d, methyl 2-methyl-3-trichlomacctyl-4//-thicno 3,2-h]pyrrole-5-carboxylate 49e, methyl 2-methyl-3-(2-methylpropanoyl)-4/7-thieno[3,2- ]pyrrole-5-carboxylate 49f, methyl 3,6-diacetyl-2-methyl-4//-thieno[3,2-h]pyrrole-5-carboxylate 50a, methyl 6-acetyl-2-methyl-3-propanoyl-4//-thieno [3,2-h]pyrrole-5-carboxylate 50b, methyl 6-acetyl-3-chloroacetyl-2-methyl-4//-thieno [3,2-h]pyrrole-5-carboxylate 50c, methyl 6-acetyl-3-dichloroacetyl-2-methyl-4//-thieno[3,2-h]pyrrole-5-carboxylate50d, methyl 6-acetyl-2-methyl-3-trichloroacetyl-4//-thieno[3,2-h]pyrrole-5-carboxylate 50e, methyl 6-acctyl-2-mcthyl-4//-thicno 3,2-h pyrrole-5-carboxylate 51 [17]...

Methylation of halothiophenes 86 and 88 was accomplished via the Stille reaction with tetramethyltin to give methylated thieno[3,2- >]pyran 87 [74] and thienyldeoxyuridine 89 [75], respectively. Analogously, the coupling of an allyl chloride, chloromethylcephem 90 and 2-tri-n-butylstannylthiophene furnished 91, an intermediate for a C(3) thiophene analog of cephalosporin [76]. 

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. 

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). 

More vigorous conditions were required for the formylation of thienothiophene 3 with an electron acceptor group in the molecule. Thus, refluxing methyl thieno[3,4-6]thiophene-2-carboxylate, iV-methyl-formanilide and phosphorus oxychloride for 1 hour gave a mixture (1 1)... 

The 2-ethyl derivatives of thienothiophenes 1 and 2 form in high yields the corresponding monoacetoxymercury compounds which considerably differ in their melting-points and may be used for identification of the isomeric thienothiophenes. Bisacetoxymercury compounds can be formed from 2,5-dialkyl thienothiophene 1. 2-Ethyl-5-methyl-thieno[2,3-6]thiophene with mercuric acetate in methanol produced the... 

Methyl thieno[3,2-r/][l,2,3]thiadiazole-6-carboxylate (MTTC) 50 has been shown to deactivate the P450 enzyme-catalyzed oxidation of 1-phenylethanol to acetophenone <1997B7209>. It was postulated that this was due to preferential enzymatic oxidization of MTTC. GC-MS analysis of the enzymatic oxidation products of compound 50 showed the major product to have a molecular mass of 188. Compounds 51 or 52 are possible structures assigned to this molecular mass although no other analytical method had been used for confirmation. 

Diazotization of aminothiophene and the Hurd-Mori reaction <1955JA5359> are two popular methods for synthesis of thieno[2,3- -l,2,3-thiadiazoles. Amine 128 gave only a poor yield of methyl thieno[2,3-/7]-l,2,3-thiadiazole-6-carbox-ylate 131a when subjected to acidic diazotization conditions (Scheme 14). The fully substituted thiophenes 129 and 126 underwent cyclization in much greater yields under similar conditions <1999M573>. Protected amines 127 and 130 also gave a better yield of the cyclized product than the unprotected amine 128 <1999JHC761>. 

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>. 

Hurd-Mori reaction on hydrazone 147 produced methyl thieno[3,4-r/ -l,2,3-thiadiazole-6-carboxylate 148 along with methyl thieno[3,2-r7 -l,2,3-thiadiazole-5-carboxylate 135 and methyl 5,6-dihydrothieno[3,2-r7 -l,2,3-thiadiazole-5-carboxylate 149 in a ratio of 1 2.6 0.5 (72% combined yield). Conversion of compound 149 to the fully aromatized 135 is accomplished by treatment with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) in refluxing benzene for 10 days (Scheme 15). A modified reaction mechanism for the Hurd-Mori reaction is also presented here <1998H(48)259>. 

Acetylation of 3-ethylthieno[2,3-6]thiophene (21) gives 2-acetyl-3-ethylthieno[2,3-6]thiophene,2 and acetylation of 3-methylthieno[3,2-61-thiophene (27) proceeds similarly (92% yield), while 2-ethyl-6-methyl-thieno[3,2-6]thiophene is converted into 2-acetyl-5-ethyl-3-methyl-thieno[3,2-6]thiophene (73%).43... 

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. 

The stable did -azulcnyl)thieno[3,2-9]thiophene-2,5-diyl spacers 78a and 78b were prepared by hydride abstraction of the corresponding 2,5-bis[bis(methyl and 3,6-di-tert-butyl-l-azulenyl)methyl]thieno[3,2-9]thiophenes 77a and 77b, the synthesis of which was established by the reaction of 1-methyl- and 1,6-di-t-butylazulcncs 75a and 75b with thicno 3,2-9 thiophene-2,5-dicarbaldehyde 76 (Scheme 11). The dications 76 showed high stability with large pA"R+ values. The electrochemical behavior of 78 was examined by cyclic voltammetry (CV). Chemical reduction of 78 with Zn powder in acetonitrile afforded 79 as deep-colored crystals, which exhibited rather high... 

That electrophilic attack on thienopyridines can occur on neutral or positively charged species receives support from the observations of Dressier and Joullie.48 These workers found that, under conditions where complete protonation of nitrogen was not to be expected, 7-methyl-thieno[2,3-c pyridine (56 pA, 5.81) underwent the Friedel-Crafts reaction whereas 4-methylthieno[3,2-c]pyridine (57 ptfa 6.17) did not, which the authors ascribed to the effect of the stronger basicity of 57. 

Cyclization of isomeric thiophenes 65 and 66 containing the aldehyde function and the SCH2C02Me group in positions 2 and 3 by reaction with l,5-diazabicyclo[4.3.0]-non-5-ene (DBN) affords methyl thieno[2,3- )]- (67) and -[3,2-i ]thiophene-2-carboxylates (68), respectively (91JMC1805). 

Diethyl 3,4-bis((diethoxyphosphoryl) methyl) thieno[2,3-b]thiophene-2,5-dicarboxylate [3e colorless oil, P(OEt)3i 2.5 equiv ZnBr2 0.4 equiv reaction time 7 h yield 85%]... 

UV, 6, 1032 (74JA4268) 47/-Thieno[3,4-c]pyrrol-5-ium-4-ide, 5-methyl-UV, 6, 1032 (74JA4268) 47/-Thieno[3,4-c]pyiTol-5-ium-4-ide, 5-phenyl-UV, 6, 1032 (74JA1817) l-(2-Thienyl)ethyl acetate kinetic data, 4, 952 (77AHC(21)119>... 

Thieno[2,3-e]azaborine-6-carboxylic acid, 1,2-dihydro-2-phenyl-3-(2-thienyl)-methyl ester... 

Thieno[3,4-d]oxazole-3a(4H)-carboxylic acid, dihydro-2-methyl-synthesis, 6, 1020 Thieno[2,3-d Joxazoles synthesis, 6, 990 Thieno[3,2-g]pteridine structure, 3, 284 lH-Thieno[3,4-c]pyran-2-ones synthesis, 4, 1032 Thienopyrazines synthesis, 4, 1022-1024 Thieno[2,3-6]pyrazines, 4, 1023 electrophilic substitution, 4, 1024 Thieno[3,4-6]pyrazines, 4, 1024 Thieno[3,4-c]pyrazole, 4,6-dihydro-3-hydroxy-carbamates... 

Thieno[2,3-6]pyridine-5-catboxylic acid, 4-chloro-2-methyl-... 

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