Reimer-Tiemann reaction limitations

While the Friedel-Crafts acylation is a general method for the preparation of aryl ketones, and of wide scope, there is no equivalently versatile reaction for the preparation of aryl aldehydes. There are various formylation procedures known, each of limited scope. In addition to the reactions outlined above, there is the Vdsmeier reaction, the Reimer-Tiemann reaction, and the Rieche formylation reaction The latter is the reaction of aromatic compounds with 1,1-dichloromethyl ether as formylating agent in the presence of a Lewis acid catalyst. This procedure has recently gained much importance. 

The applicability of the Reimer-Tiemann reaction is limited to the formylation of phenols and certain reactive heterocycles like pyrroles and indoles. Yields are usually below 50%. In contrast to other formylation procedures, the Reimer-Tiemann reaction is ort/zo-selective it is therefore related to the Kolb e-Schmitt reaction. 

The opening of 9a jlOce -oxides by Grignard reagents (Scheme 74) and the Michael reaction with 17a-ketones (Schemes 104 and 105) have been used to an extremely limited extent. The passage from estrogens to 10-methylsteroids has been effected in low yield by Birch reduction and subsequent reaction with carbenes (Scheme 39). The Reimer—Tiemann reaction has been used for the same purpose [53] with the reaction (70) (71)... 

Although 4-hydroxybenzaldehyde can be made by the saligenin route, it has been made historically by the Reimer-Tiemann process, which also produces sahcylaldehyde (64). Treatment of phenol with chloroform and aqueous sodium hydroxide results in the formation of benzal chlorides, which are rapidly hydrolyzed by the alkaline medium into aldehydes. Acidification of the phenoxides results in the formation of the final products, sahcylaldehyde and 4-hydroxybenzaldehyde. The ratio of ortho and para isomers is flexible and can be controlled within certain limits. The overall reaction scheme is shown in Figure 1. Product separation is accomphshed by distillation, but this process leads to environmental problems because of the quantities of sodium chloride produced. 

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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