Dichlorocarbene reaction with phenol

In alkaline solution, the phenol 1 is deprotonated to the phenolate 4, which reacts at the ort/zo-position with dichlorocarbene 3. The initial addition reaction product 5 isomerizes to the aromatic o-dichloromethyl phenolate 6, which under the reaction conditions is hydrolyzed to the o-formyl phenolate." ... 

Phenols are smoothly converted into phenolic aldehydes by reaction with chloroform in the presence of base (the Reimer-Tiemann reaction). This overall formylation reaction is of interest in that it involves the generation from chloroform and alkali of the reactive intermediate, dichlorocarbene (2). This effects electrophilic substitution in the reactive phenolate ions giving the benzylidene dichloride (3) which is hydrolysed by the alkaline medium to the corresponding hydroxyaldehyde. The phenolic aldehyde is isolated from the reaction medium after acidification. 

Regioselective reaction of phenols. Reaction of phenols with chloroform in aqueous alkaline solution catalyzed by P-cyclodextrin results in virtually complete attack at the para-position by dichlorocarbene to give, after hydrolysis, 4-hydroxybenzaldehydes. If the para-position is substituted, 4-(dichloromethyl)-2,5-cyclohexadienones are obtained as the major product. The selectivity results from formation of a ternary complex from P-cyclodextrin, chloroform, and the phenol. ... 

Phenols react with chloroform in the presence of hydroxide ion in water to give o- and jp-hydroxybenzaldehydes. The steps of the reaction are (1) the formation of dichlorocarbene, as shown in Example 4.22 (2) nucleophilic reaction of the phenoxide with the electrophilic carbene and (3) hydrolysis. 

The reaction of phenol with chloroform and alkali (dichlorocarbene) at 65 to 70 °C gives salicylaldehyde (Reimer-Tiemann synthesis), from which coumarin is produced by reaction with acetic anhydride and sodium acetate at 135 to 155 °C (Perkin reaction). Coumarin is used as a perfume and fragrance. 

Despite the long history of the Reimer-Tiemann reaction, little has been reported in the phase transfer literature on this subject. There appears to be a single report of work in which phase transfer generated dichlorocarbene has been added to a phenolic substrate [58]. 4-Methyl-2,6-nonamethylenephenol reacts with dichlorocarbene in chloroform solution to yield the product of ortho insertion (76%) as shown in equation 2.39. The reactions of dichlorocarbene with several other lipophilic phenols are likewise reported [58]. 

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. 

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. 

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 best way to introduce the formyl group in the proper position is through a Reimer-Tiemann reaction. This involves treating a phenol with chloroform in the presence of base. Under these conditions, chloroform sequentially loses a proton and a chloride anion in an a-elimination (elimination with both leaving groups on same carbon) to form a dichlorocarbene. 

In Equation (6), the resulting dichlorocarbene and the phenolate ion tmdergoes a reversible reaction to form an intermediate, which subsequently loses a proton and then gains a proton to 3deld the benzylidene dichloride. The benzylidene dichloride on being subjected to a treatment with an alkali followed by the hydronium ion yields the corresponding ort/io-hydroxy aldehyde (or salicylaldehyde). 

The structure of the ternary inclusion complex composed of 3-cyclodextrin, phenol, and, chloroform or carbon tetrachloride, formed in the reaction mixture, is determined by NMR spectroscopy. The selective catalysis by cyclodextrin was attributed to the regulation of molecular conformation of substrates with respect to dichlorocarbene, to trichloromethy1 cation, or to allyl cation in the ternary molecular complex. 

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