Reimer-Tiemann formylation

Hydroxy-4-methylthiazole failed to react when submitted to Friedel-Crafts benzoylation conditions (349) on the other hand, it reacted normally in Gattermann and in Reimer-Tiemann formylation reactions, affording the 5-formyl derivative (348). 4-Methylthiazole is insufficiently activated and fails to react under the same conditions. 2,4-Dimethylthiazole undergoes perfluoroalkylation when heated at 200° for 8 hr in a sealed tube with perfluoropropyl iodide and sodium acetate (116) (358). 

The idea that dichlorocarbene is an intermediate in the basic hydrolysis of chloroform is now one hundred years old. It was first suggested by Geuther in 1862 to explain the formation of carbon monoxide, in addition to formate ions, in the reaction of chloroform (and similarly, bromoform) with alkali. At the end of the last century Nef interpreted several well-known reactions involving chloroform and a base in terms of the intermediate formation of dichlorocarbene. These reactions included the ring expansion of pyrroles to pyridines and of indoles to quinolines, as well as the Hofmann carbylamine test for primary amines and the Reimer-Tiemann formylation of phenols. 

Very few reactions of carbenes with heterocyclic systems containing more than one hetero atom have been studied. They are confined to variants of the Reimer-Tiemann formylation of thiazoles, pyra-zoles, iminazoles, and indolizines/ and ring expansion does not appear to have been observed. 

The Reimer-Tiemann formylation of several phenols in the quinohne and pyrimidine series is known, but the reaction is unsuccessful with hydroxypyridines 3-hydroxypyridine gave a polymer. No 2-hydroxyquinoline appears to have been studied the 4-hydroxy... 

H2SO4 alone destroys ring), (ii) Reimer-Tiemann formylation 2-pyrrolecarboxaldehyde (2-formylpyrrole),... 

Indole, like benzothiophene, reacts with electrophiles to give preferentially -substituted products. Bromination241-243 in dioxane or pyridine, nitration by ethyl nitrate,244 chlorination by sulfuryl chloride,245 iodination in aqueous solution,246, 247 Vilsmeier and Reimer-Tiemann formylations,248-261 diazo coupling,252 thio-cyanation,263 and nitrosation254 all give the 3-substituted indoles, practically free from other isomers. 

Reimer-Tiemann formylation of phenols.1 Yields in this reaction can be increased by use of solid, powdered NaOH and addition of water (2 equiv. per phenol). 

We include in this section formylation reactions involving carbon monoxide, hydrogen cyanide, formyl fluoride and dichloromethyl alkyl ethers." The Vilsmeier and Reimer-Tiemann formylation reactions are the subjects of other chapters (Volume 2, Chapters 3.4 and 3.5). 

A combined Reimer-Tiemann formylation and Claisen condensation procedure with nitromethane has been described for 4 hydroxybenzoic acid constituting... 

A well-established cycloaddition of pyrroles is the [2+2] cycloaddition with dichlorocarbene. This is in competition with the Reimer-Tiemann formylation ... 

The Reimer-Tiemann formylation of phenols with chloroform was attempted under sonication, in order to improve the frequently unsatisfactory yields. Optimal conditions make use of aqueous sodium hydroxide, and the electrophilic attack of the carbene on the ring is followed by the hydrolysis of the dichloromethyl group to the aldehyde. The advantages of the sonochemical method are not clearly apparent. The positive effect of sonication is limited to the reaction of 4-chlorophenol, and 4-methyl- and 4-methoxyphenol react with a yield lower than conventionally found. 

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