2-Formyl-5-methylthiophen

J.14) 2-Thiophenecarboxaldehyde, 5-methyl-, 5-methylthiophene-2-carbaldehyde, 2-formyl-5-methylthiophene 13679-70-4] FEMA 3209... 

This activation of the ortho position is most strikingly illustrated in the reactivity of 2,5-dimethylthiophene, which competitive experiments have shown to undergo the SnCb-catalyzed Friedel-Crafts reaction more rapidly than thiophene and even 2-methylthiophene. The influence of the reagent on the isomer distribution is evident from the fact that 2-methoxythiophene is formylated and bromi-nated (with A -bromosuccinimide) only in the 5-position. Similarly, although 3-bromo-2-methylthiophene has been detected in the bromi-nation of 2-methylthiophene with bromine, only the 5-isomer (besides some side-chain bromination) is obtained in the bromination of alkylthiophenes with A -bromosuccinimide. ° However, the mechanism of the latter type of bromination is not established. No lines attributable to 2-methyl-3-thiocyanothiophene or 2-methyl-3-chIoro-thiophene could be detected in the NMR spectra of the substitution products (5-isomers) obtained upon thiocyanation with thiocyanogen or chlorination with sulfuryl chloride. 2-Methyl- and 2-ethyl-thiophene give, somewhat unexpectedly, upon alkylation with t-butyl chloride in the presence of Feds, only 5-t-butyl monosubstituted and... 

Substituted 3-hydroxythiophenes are convenient starting-points for the synthesis of the thieno[3,2-Mthiophene system. Shvedov et obtained 50% of 3-chloro-3-ethoxycarbonyl-5-methylthiophene-2-aldehyde (110) from 3-ethoxycarbonyl-4-hydroxy-2-methylthiophene (109) by Vilsmeier formylation at 100°. Reaction with thioglycolic ter formed 3-ethoxycarbonyl-5-methoxycarbonyl-2-methylthieno[3,2-6]-thiophene (111) [. (36)]. 

Thiophene-2-carbaldehyde has become extremely cheap and easily available through the Vilsmeier formylation of thiophene. The reactions of thiophene substrates with several iminium salts have been investigated (B-76MI31400). 3-Phenylthiophene gives 4-phenylthiophene-2-carbaldehyde with chloromethylene iminium ion. In the case of 2-methoxy-5-methylthiophene, a dealkylation takes place above 50-70 °C. If the intermediate iminium salt (91) is formed at 20 °C and then hydrolyzed, the aldehyde (92) is obtained. 

Thiophenes thiophene tetrahydrothiophene-3-one 2-butylthiophene 2-formy1-3-methylthiophene 2-pentylthiophene 2-hexylthiophene 2-heptylthiophene 2-formyl-5(or 3)-pentylthiophene 3.5 10.5 57.2 29.8 13.1 42.0 1.8 15.6... 

Scheme 9.12 shows the synthetic route. [4-Methyl-2,5-bis(trimethylsilylethy-nyl)-3-thienyl]heptafluorocyclopentene (31) was prepared from 3-bromo-4-methylthiophene (28) in three steps. 2 -methoxy derivative 33 was synthesized by the coupling of 31 with lithiated 32. After desilylation with KOH, Sonogashira coupling with bromoformyl compounds gave bisformylated diarylethenes 34. Formyl derivative 34 was converted into nitroxide radical 27a. 

A kinetic study of the Vilsmeier-Haak formylation of thiophene derivatives in dichloroethane solution has been recently reported.156 Reactions of thiophene and 2-methylthiophene follow third-order kinetics, first-order in substrate, dimethylformamide (DMF), and phosphorus oxychloride. These results are in agreement with a mechanism involving a rapid preequilibrium step leading to an... 

Kinetic investigation of the formylation of thiophene and of 2- and 3-methylthiophene in 1,2-dichloroethane showed the reactions to be first order in each of aromatic, DMF, and POC1,. However, for the much more reactive 2-methoxythiophene, the reaction is second order overall, and zeroth order in aromatic. This is consistent with a slow pre-equilibrium to form the electrophile [(Me2NC+HCl)P02Cl2-], which reacts with the aromatic to give the Wheland intermediate in a step which is ratedetermining except when the aromatic is very reactive, whereupon this step becomes relatively fast. Finally, the intermediate decomposes to products in a fast step [72JCS(P2)2070]. 

J.13) 2-Thiophenecarboxaldehyde, 3-methyl-, 3-methylthiophene-2-carbaldehyde, 2-formyl-3-methylthiophene [5834-16-2]... 

Figure 6 NOED spectra for structure elucidation of 2-ethyl-4-formyl-3-methylthiophene 3 showing signal intensifications from irradiation of a) formyl group, b) aromatic methine proton, c) methylene protons, and d) methyl group.

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