5- Methylthiophene-2-aldehyde

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)]. 

The Stobbe condensation between 5-methylthiophen-2-aldehyde and dimethyl succinate has been studied. Through reduction of a mixture of thiophen-2-aldehyde and acrolein the vinylthienyl glycol (160) was obtained... 

Aldol-type condensations between but-2-enolides and carbonyl compounds constitute probably the most flexible routes to 4-ylidene-butenolides and 4-ylidenetetronic acids. One of the first applications of this general approach was in the preparation of (130) from but-2-enolide (129 a) employing aqueous sodium hydrogen carbonate as base 114). Bohlmann and Zdero 34) later described a synthesis of the naturally occurring thiophene (131) involving condensation between butenolide (129 b) and 5-methylthiophene-2-aldehyde in the presence of piperidine acetate in glacial acetic acid at 80°. 

Synthetic routes that access appropriately substituted thienobenzazepines are also quite important for medicinal chemistry stracture activity relationship studies, and many involve similar bond connectivity strategies. One notable example employs the use of conunercially available 4-methyl-3-nitrophenol (Scheme 6.3). Methylation of the phenol followed by bromination, hydrolysis, and oxidation of the benzylic alcohol afforded aldehyde 9 in quantitative yield. Treatment of this aldehyde with 5-lithio-2-methylthiophene provided, after dehydroxylation, nitro intermediate A in good overall yield. Reduction of the nitro functionality and treatment with phosgene presented the corresponding isocyanide which upon cychzation using aluminum trichloride in a Friedel-Crafts fashion afforded the... 

A New Improved Synthesis of Tricycle Thienobenzazepines Apphcation of chemistry recently developed by Knochel" combined with the well-described halogen dance (HD) reaction, allowed preparation of our key intermediate A in only three synthetic transformations (Scheme 6.4). In this respect, treatment of 2-bromo-5-methylthiophene with hthium diisopropylamide followed by dimethylformamide afforded aldehyde 11 in good yield, lodo-magnesium exchange with conunercial 4-iodo-3-nitro anisole followed by reaction with 11 afforded the thiophene catbinol 12. Dehydroxylation of 12 provided our key intermediate A which presented the requisite functionality to examine our approach to the construction of the seven-member ring system. 

Oxidation of the aldehyde was not used earlier because of the difficulty of obtaining the aldehyde, which is now readily available by the Sommelet synthesis from 3-thenyl bromide. Campaigne and LeSuer 7 also used alkaline permanganate as the oxidizing agent, but the yields decreased to 40-60%. The present procedure gives an over-all yield from 3-methylthiophene of about 45%. 

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. 

The preparation of 3-methvl-2-f3 7Ur-trimethvldodecvrithiophene. This compound, which has a carbon skeleton resembling that of phytane, is often a major component of certain immature sediments Q). Previous syntheses of this compound have used the acylation method whereby 3-methylthiophene is acylated with 3,7,11-trimethyldodecanoic acid (1, 8). Reference to Figure 5 indicates that the required compound will be accompanied by the 2,4-isomer and this is indeed the case. The pure compound can, however, be prepared using a lithiated alkylthiophene and an aldehyde (Figure 23). 

MWCNTs/poly(3- methylthiophene) (MWCNT-PMTH) In-situ chemical polymerization Pellets Methane, acetone, acetaldehyde, benz-aldehyde, tetrahydro-furan, methanol, and ethanol [36]... 

E.S.R. Spectra.— The e.s.r. spectra of some thienylphenyl and trithienyl-methyl radicals have been analysed. The complex e.s.r. spectrum that arises on treatment of 2,2 -bithienyl with potassium at — 80 °C is interpreted as due to two rotamers of the radical anion of 2,2 -bithienyl. It is believed that the two aromatic rings are held in a planar or nearly planar conformation, where the sulphur atoms are in a cw- or /I a/w-position, for a sufficient time for each rotamer to give an individual spectrum. 2-Phenyl-thiophen is claimed to behave similarly. The ketyls from thiophen-2-aldehyde and 2-acetylthiophen also give overlapping spectra, assigned to the 0-cis- and O-frawj -isomers present in unequal amounts. Well-resolved e.s.r. spectra of the 2- and 3-thenyl and 5-methyl-2-thenyl radicals, produced by the reaction of t-butoxyl radicals with the methylthiophens, were also obtained, and the spin distributions in the radicals studied were compared... 

The radical products of low-temperature reactions of hydrogen atoms with a number of thiophen derivatives in the solid phase have been studied. In the case of 2-methylthiophen, thiophen-2-aldehyde, and 2-acetothienone, e.s.r. studies indicate that the hydrogen atoms are added to the ring at the C=C bonds, forming radicals with an unpaired electron on the carbon atom. In the interaction of 3-methylthiophen with hydrogen... 

The introduction of hydroxymethyl groups into thiophenes is possible by the reaction of thienyllithiums with ketones or aldehydes (Scheme 36, Table 22) [227-229]. Electron-rich heterocycles like 2-methylthiophene 32 can be treated with l-[(triphenylphosphoranyUdeneamino)methyl]-l,2,3-benzotriazole 90, which serves as aminomethylation agent, forming the corresponding product 91 in moderate yield (Scheme 37) [230]. 

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