Reimer-Tiemann reaction mechanism

The structure of the product of the Reimer-Tiemann reaction of 1,2,3-trimethylindole (24) has been confirmed as 3-dichloromethyl-1,3-dimethyl-2-methyleneindoline (25) by spectroscopy and oxidation to the iV -methyloxindole when the dichlorocarbene was generated under neutral conditions a ring-expanded product, 3-chloro-1,4-dimethyl-2-methylene-1,2-dihydroquinoline (26) could be isolated and oxidized to the corresponding a-quinolone. These reactions presumably proceed by mechanisms similar to those discussed for 2,3-di-... 

Problem 19.18 Outline a mechanism for the (a) Kolbe reaction, (h) Reimer-Tiemann reaction. (a) Phenoxide carbanion adds at the electrophilic carbon of CO,. 

The Reimer-Tiemann reaction used to be an important way of making ortho-substituted phenols, but the yields are often poor, and modern industly is wary of using large quantities of chlorinated solvents. On a small, laboratory scale it has largely been superseded by ortholithiation (Chapter 9) and by modern methods outside the scope of this book. The mechanism probably goes something like this. 

Treatment of a phenol with chloroform (trichloromethane) in the presence of hydroxide ion results in the synthesis of a 2-hydroxybenzalde-hyde through C-formylation. Dichlorocarbene, CCl2, is generated by the action of base on chloroform and this highly reactive electrophile then attacks the phenoxide. The mechanism of the Reimer-Tiemann reaction, is given in Scheme 4.12. 

Castillo, R., Moliner, V., Andres, J. A theoretical study on the molecular mechanism for the normal Reimer-Tiemann reaction. Chem. Phys. Lett. 2000, 318, 270-275. 

It is interesting to compare early experimental work with the facilities available in a modem laboratory. Von Auwers was the first to separate the chloro ketones from the normal phenolic aldehydes of the Reimer-Tiemann reaction. Identirication and strocture proof by chemical means followed. It is a tribute to von Auwers skill and insight that his identification procedures have withstood the onslaught of modem spectroscopic means. Although the chloro ketones (equations 8-10) have been called the abnormal products of the reaction, in cases where the ortho and para positions are occupied (see equation 10) only ketonic material is obtained.In fact, the presence of the dichloro ketones provides one of the better arguments for the intermediacy of dichlorocarbene in the reaction mechanism. ... 

The formation of all of the reaction products, phenolic aldehydes, dichloro ketones and ring-expansion products, can be explained satisfactorily by postulating the carbene intermediate originally proposed by Mine (Scheme 3). The only products that might be thought of as resulting from direct nucleophilic displacement of phenolate anion on chloroform are the orthoformic esters (e.g. 2) formed in low yields in most Reimer-Tiemann reactions (and rarely isolated or identified). However, even these can result from a version of the Hine mechanism. 

Phenol reacts with chloroform in an alkaline medium (OH ) to give rise to the formation oiortho- andpara-isomers of salicylaldehyde. The mechanism of the above reaction has already been explained earlier (under Reimer-Tiemann reaction section 4.7 J). Obviously, a mixture of bothorf/io- and para-isomers are formed simultaneously in the products of reaction however. 

It is well known that under basic conditions, phenol is converted into phenoxide and chloroform is transformed into dichlorocarbene, a highly electron-deficient species, thus the Reimer-Tiemann reaction involves the electrophilic attack of dichlorocarbene on phenoxide, followed by intermolecular proton transfer, as indicated by the deuterium and tritium isotope labeling experiment. An illustrative mechanism is thus provided for the formation of salicylaldehyde. 

A theoretical study on the molecular mechanism for the normal Reimer-Tiemann reaction ... 

Three further computational explorations of carbene reaction mechanisms have been reported. DFT study of the Reimer-Tiemann reaction (formal reaction between CCl2 and a phenoxide ion) using either potassium or sodium hydroxide as base has revealed that the active carbenic species is an alkaline carbenoid form rather than its free form as suggested earlier. DFT study of the reaction of CHF with dioxygen has confirmed fhaf fhe firsf step involves formation of the planar HFCO2 adduct. The initial steps of 2,5-dimethylfuran thermal decomposition have been computationally identified as scission of the C—H bond in the methyl side chain and subsequent formation of ft- and a-carbenes (39) and (40) via [3,2]-H and [2,3]-methyl shifts, respectively (Scheme 6). Once generated, carbenes (39) and (40) are believed to follow diverse fragmentation pathways. ... 

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