Reimer-Tiemann

C7H6O2 Oily liquid of aromatic odour b.p. 196°C. (t is prepared by the action of chloroform and caustic potash on phenol (the Reimer-Tiemann reaction) or by the oxidation of the glucoside salicin. It is easily reduced to salicyl alcohol or oxidized to salicylic acid. 

From phenols by interaction with chloroform and sodium hydroxide solution (Reimer - Tiemann reaction), for example ... 

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). 

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. 

Phenyhsonitrile has a powerful characteristic odor it is used as a qualitative test (the carbylamine test) for chloroform or primary aromatic amines. Chloroform reacts with phenols in alkaline solution to give hydroxyaromatic aldehydes in the Reimer-Tiemann reaction eg, phenol gives chiefly Nhydroxyben2aldehyde and some sahcylaldehyde (11) (see Hydroxybenzaldehydes). 

Aminotriazole is carboxylated at the 5-position by heating with aqueous sodium bicarbonate in a Kolbe-type reaction (7lJCS(C)l50l). 2-Thiazolinones undergo the Gatter-mann and Reimer-Tiemann reactions at the 4-position, and 3- and 4-pyrazolinone anions on alkylation give 4-alkyl as well as O- and N-alkyl derivatives. 

Using Reimer-Tiemann reaction conditions on 3-alkyl-6-hydroxy-1,2-benzisoxazoles results in formylation occurring at the 7-position (77UC(B)1056). 

Reimer-Tiemann reaction, 2, 209-210 Oxycarboxin as fungicide, 1, 193 Oxydimethiin... 

Pyrrolo[2,3-6]pyridine, 2-methyl-Reimer-Tiemann reaction, 4, 508 Pyrrolo[2,3-6]pyridine, 4-methyl-hydrogen exchange, 4, 502 reaction with aldehydes, 4, 503 reaction with benzaldehyde, 4, 511... 

REIMER - TIEMANN Phenol Pormylation Formylation ot phenols with CHCt3-base (dichiorocarbene)... 

The Ciamician-Dennstedt reaction can be thought of as the complement to the Reimer-Tiemann reaction (Scheme 8.3.2). The first step of both reactions is cyclopropanation of one of the carbon-carbon double bonds of a pyrrole with a dichlorocarbene, resulting in intermediate 3. The Ciamician-Dennstedt reaction results from cleavage of the internal C-C bond and elimination of chloride (path a), while the Reimer-Tiemann reaction results from cleavage of the exocyclic bond, and subsequent hydrolysis of the dichloromethyl moiety to furnish aldehyde 5 (path b). 

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. 

Under conditions more similar to those of the Reimer-Tiemann reaction 3-bromopyridine was obtained from pyrrole and bromo-form. Treatment of pyrrole with chloroform and aqueous alkali gave pyrrole-2-aldehyde curiously, the formation of 3-chloropyridine under these conditions does not appear to have been reported, in spite of being frequently quoted. However, indole gave both indole-3-aldehyde and 3-chloroquinoline under these conditions [Eq. (10)]. 

The Reimer-Tiemann reaction has also been used to formylate 2,5-dimethylpyrrole and its iV-methyl derivative and indoles having methyl, methoxyl, and phenyl substituents. Significantly, 3-methylindole gave only 3-chloro-4-methylquinoline. ... 

A variant of the Reimer-Tiemann reaction, using chloroform or bromoform with ethanohc sodium ethoxide, has been apphed (mainly by Plancher and co-workers) to certain pyrroles and indoles with interesting results. Thus Bocchi has shown that 2,5-dimethylpyrrole gave 3-halogeno-2,6-dimethylpyridine, and 2,4-dimethylpyrrole with bromoform gave two isomeric bromodimethylpyridines [Eq. (11)]. 

The latter reaction has been repeatedly misquoted (e.g. ref. 50) as involving 2,3-dimethylpyrrole, but the Reimer-Tiemann reaction of this pyrrole has not been investigated. In this case the methyl groups should activate the 2,3-bond sufficiently to make the 3-halogeno-2,4-dimethylpyridine the major—if not the sole— product. 

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-... 

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... 

There are a few scattered references to the reaction of nonphenohc six-membered heterocyclics with dichlorocarbene under Reimer-Tiemann conditions. Thus a mixture of 2-methylpyridine, chloroform, and sodium hydroxide is reported to contain sorbic acid and cyanide ions after standing for several months. Another similar reaction of... 

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