Thiophene-3-carbaldehyde, reaction with

Benzo[6]thiophene-2-carbaldehyde can be converted to 2-(l, 2 -epoxyethyl)-benzo[6]-thiophene by reaction with trimethylsulfoxonium iodide and sodium hydride or with diazomethane. However, the 3-carbaldehyde is reported to give the 3-acetyl derivative on treatment with diazomethane (Scheme 120) (70AHC(ll)177). 

Pyridine ring construction according to strategy P is based on the one-step formation of the C(4)-N(5) and C(7)-C(7a) bonds. For example, this approach provides the basis for the synthesis of the simplest isomeric dithienopyridines (1988CS281). The Stille cross-coupling reaction of 2-tributylstannyl-3-thiophene-carbaldehyde (256) with thienylcarbamates 115, 257, and 258 affords the target compounds 259-261, respectively, in different yields. 

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 C-thioacylation of l-alkyl-2-methyltetrahydropyrimidines and 1,2-dimethyl-dihydroimidazole has been achieved by reaction with thiophene-2-carbaldehydes in the presence of sulfur (Scheme 115) (82T1673). The yield of product is better with thiophene-2-carbaldehydes (30-40%) than with benzaldehyde. 

Thenaldehyde (thiophene-2-carbaldehyde) is readily available via the Vilsmeier-Haack reaction of DMF with thiophene catalyzed by phosphorus oxychloride. The Sommelet reaction with 2-chloromethylthiophene also gives reasonable yields (63AHC(l)l). Likewise, thiophene is readily acylated with acyl anhydrides or acid chlorides (equation 14), using mild Friedel-Crafts catalysts, such as tin(IV) chloride, zinc chloride, boron trifluoride, titanium tetrachloride, mercury(II) chloride, iodine and even silica-alumina gels or low-calcium-content montmorillonite clays (52HC(3)l). 

The use of methyltriphenylphosphonium bromide and MeSOCH2 on 5-bromo-2-thienyl-thiophene-2-carbaldehyde (128) furnished the corresponding olefin 133. The reaction with propyne in this case furnished a natural bithiophene 134 isolated from Tagetes minuta (86G747). 

Structural changes affect seriously an electrophilic substitution orientation in pyrroles owing to their low positional selectivity in reactions with electrophiles. Thus, in contrast to thiophene, selenophene, and, especially, furan analogues, even a relatively weak type 11 substituent in position 2 of the pyrrole ring is capable of overcoming the a-oiienting effect of the heteroatom and directs an electrophile preferably to the position 4 (68JCS(B)392). N-(p-Nitrophenyl)pyrrole-2-carbaldehyde... 

A very convenient method for the synthesis of (158) consists in the side-chain bromination of 2-thienyl ethyl ketone followed by reaction with sodium methoxide in methanol and with methanesulphonyl chloride in pyridine, which gave (157) in 88% yield. Treatment of (157) with calcium carbonate led to 1,2-rearrangement of the thienyl group to give (158). Metal complexes of s> -thiophen-2-aldoxime, thiophen-2-carbaldehyde 2-benzothiazolylhydrazone, and thiophen-2-carbaldehyde thiosemicarba-zone have been studied. 

Trialkylsilicon, germanium or tin derivatives have been introduced at position 5 of thiophene-2-carbaldehyde via lithiation <92S954>. The first step is the protection of the aldehyde as the amino-alkoxide by reaction with lithium A(-methylpiperazide (LNMP). Subsequent treatment with BuLi followed by R MCl and hydrolysis by cold brine gave the desired products. 

Condensation of thiophene-3-carbaldehyde 38 with malonic acid (Doebner reaction) in a mixture of pyridine (Py) and piperidine (Hp) with heating affords ( )-3-(3-thienyl)acrylic add (42), whose treatment with thionyl chloride in Py produces 3-chlorothieno[2,3-6]thiophene-2-carboxylic add chloride (43) (72ACS2982,... 

The multistep synthesis involving aldol condensation of thiophene-3-carbaldehyde 38 with malonic acid or the Heck reaction using 3-bromothiophene 30 or 4-bromothiophene-2-carboxylate produced thieno[3, 2 4,5]thieno[2,3-c]quinolones 82, which exhibit high antitumour activity (2002CPB656). 

A-Vinylic phosphazenes, are useful building blocks, that have been used in Aza-Wittig reactions with unsaturated aldehydes to form 3-azatrienes through a [2 -I- 21-cycloaddition-cycloreversion sequence. " The presence of an alkyl substituent in position 3 of A-vinylic phosphazenes increases the steric interactions, and [4 + 2] periselectivity (1,4 addition) is observed." Other Aza-Wittig reactions include the reaction of iminophosphorane (60) with aromatic isocyanates to obtain, inter alia, useful carbodiimides for the selective synthesis of pyrimidones." Also the iminophosphorane (61) was reacted with furan-2-carbaldehyde, thiophene-2-carbaldehyde, furan-3-carbaldehyde, and thiophene-3-carbaldehyde to give, depending on temperature and aldehyde, trans imines or mixtures of trans and cis imines." " The... 

Usually formylation of thiophenes is possible through a direct Vilsmeier-Haack reaction [208, 209]. Alternatively, thiophene-carbaldehydes, for example, 78 and 80, can be prepared by the reaction of thienyllithiums with iV,iV-dimethylformamide (Scheme 33, Table 20) [210, 212, 213, 215-219]. Notably, thiophene-3-carbaldehyde derivatives are easily accessible using this formylation methodology. 

The copolymer 174 was prepared from diaUcyl thienylated benzodithiophene (173) and perfluororalkyl-carbonyl substituted thieno[3,4-h]thiophene (172) monomers (Scheme 41). Thus, reaction of thieno[3,4-6]thiophene-2-carbaldehyde (150) with heptadecafluorooctyl iodide in the presence of methyllithium to form 170 was followed by oxidation with Mn02 giving ketone 171. Bromination with two equivalents of NBS furnished dibromide 172, and this was Stille cross-coupled with 173 in the presence of Pd2(dba)3 to obtain the copolymer 174 [63]. 

The carbonyl reactivity of pyrrole-, furan-, thiophene- and selenophene-2- and -3-carbaldehydes is very similar to that of benzaldehyde. A quantitative study of the reaction of iV-methylpyrrole-2-carbaldehyde, furan-2-carbaldehyde and thiophene-2-carbaldehyde with hydroxide ions showed that the difference in reactivity between furan- and thiophene-2-carbaldehydes was small but that both of these aldehydes were considerably more reactive... 

The reactions of substituted furo[3,2- ]pyrrole-5-carbohydrazides with 5-arylfuran-2-carbaldehydes, 4,5-disubsti-tuted furan-2-carbaldehydes, and thiophene-2-carbaldehyde have been studied <2005CEC622>. The advantage of microwave (MW) irradiation on some of these reactions was reflected in the reduced reaction time and increased yields (Table 8). The series of substituted hydrazones 241-246 was obtained from these... 

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