Phenols Reimer-Tiemann reaction

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 ... 

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). 

The formylation of a phenol 1 with chloroform in alkaline solution is called the Reimer-Tiemann reaction. It leads preferentially to formation of an ortho-formylated phenol—e.g. salicylic aldehyde 2 —while with other formylation reactions, e.g. the Gattermann reaction, the corresponding /jara-formyl derivative is obtained as a major product. The Reimer-Tiemann reaction is mainly used for the synthesis of o-hydroxy aromatic aldehydes. 

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 Reimer-Tiemann reaction of phenol with chloroform, in the presence of 50% NaOH, gives a much higher ratio of para to ortho hydroxy benzaldehyde when polyethylene glycol is used as compared to the established procedure without any addition of a hydrotope. A para to ortho ratio of 1 1 has been realized (Neumann and Sasson, 1986). 

Under suitable conditions, this can be a useful preparative method for cyclopropanes another preparative trapping reaction of CC12 is its electrophilic attack on phenols in the Reimer-Tiemann reaction (p. 290). 

Because of the differential partitioning of hydroxide and phenoxide anions into organic solvents by quaternary ammonium cations, the catalysts generally have little effect on the Reimer-Tiemann reaction of phenols with dihalocarbenes [15]. Cetyltrimethylammonium bromide has been used in the two-phase dichloromethyl-ation of polysubstituted phenols (Scheme 7.21, Table 7.10) under Makosza s conditions [16,17] ring expansion of the reaction products provides an effective route to tropones. The rate of the reaction is enhanced by ultrasonic radiation [16]. 

Reimer-Tiemann reaction org chem Formation of phenolic aldehydes by reaction of phenol with chloroform in the presence of an alkali. rTm-or te-m3n re.ak-shon Reinecke s salt analychem (Ntf3)2Cr(SCN)4 NH4 H2O A reagent to detect mercury (gives a red color or a precipitate), and to isolate organic bases (such as proline or histidine). rTn-o-kez, s6lt ... 

The presence of -OH group In phenols activates the aromatic ring towards electrophilic substitution and directs the Incoming group to ortho and para positions due to resonance effect. Reimer-Tiemann reaction of phenol 5delds sallcylaldehyde. In presence of sodium hydroxide, phenol generates phenoxlde Ion which Is even more reactive than phenol. Thus, In alkaline medium, phenol undergoes Kolbe s reaction. 

Other reported syntheses include the Reimer-Tiemann reaction, in which carbon tetrachloride is condensed with phenol in the presence of potassium hydroxide. A mixture of the ortho- and para-isomers is obtained the para-isomer predominates. -Hydroxybenzoic acid can be synthesized from phenol, carbon monoxide, and an alkali carbonate (52). It can also be obtained by heating alkali salts of -cresol at high temperatures (260—270°C) over metallic oxides, eg, lead dioxide, manganese dioxide, iron oxide, or copper oxide, or with mixed alkali and a copper catalyst (53). Heating potassium salicylate at 240°C for 1—1.5 h results in a 70—80% yield of -hydroxybenzoic acid (54). When the dipotassium salt of salicylic acid is heated in an atmosphere of carbon dioxide, an almost complete conversion to -hydroxybenzoic acid results. They>-aminobenzoic acid can be converted to the diazo acid with nitrous acid followed by hydrolysis. Finally, the sulfo- and halogenobenzoic acids can be fused with alkali. 

Aldehyde formation Reimer-Tiemann reaction Treatment of a phenol with chloroform (CHCI3) and aqueous hydroxide introduces an aldehyde group (—CHO) onto the aromatic ring, generally ortho to the —OH group. A substituted henzalchloride is initially formed, but is hydrolysed by the alkaline medium. Salicylaldehyde can be produced from phenol by this reaction. Again, salicylaldehyde could be oxidized to sahcylic acid, which could be acetylated to aspirin. 

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. 

Another example of minimizing the reaction steps necessary for synthesis is the direct conversion of cresols into hydroxybenzaldehydes, replacing the Reimer-Tiemann reaction in which phenol is reacted with chloroform in the presence of KOH. Hydroxybenzaldehydes are used in pharmaceuticals, perfumes, and colors. In the direct oxidation cresols are reacted with oxygen in the presence of Cu/Co/C catalysts forming the salicylaldehyde [49]. 

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. 

Today an unequivocal determination of substituent positions on a phenol or naphthol or hydroxyaldehyde by infrared and NMR spectroscopy is usually straightforward and should always be performed routinely the major or most easily isolated product is sometimes not the expected one For example, the most easily isolated product (the first to crystallize) from a Reimer-Tiemann reaction of 3-chlorophenol is 6-chlorosalicylaldehyde, and not the 4-chloro isomer, which is the major product. 

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. 

Reimer-Tiemann Reaction. —Both the ortho- and para-hydroxy benzaldehydes are important. They may both be synthesized by what is known as the Reimer-Tiemann reaction. This consists of the interaction between a salt of a phenol and chloroform in the presence of an excess of alkali. The result is the introduction of the aldehyde group, (—CHO), into the benzene ring of the phenol as follows ... 

From Phenols by CCI4.—The Reimer-Tiemann reaction for the synthesis of hydroxy aldehydes (p. 659) is ... 

In the Reimer-Tiemann reaction, aromatic rings are formylated by reaction with chloroform and hydroxide ion." ° The method is useful only for phenols and certain heterocyclic compounds such as pyrroles and indoles. Unlike the previous formyla-tion methods (11-18), this one is conducted in basic solution. Yields are generally... 

Reimer-Tiemann reaction. Discussed in Sec. 24.12. Only for phenols. 

Reimer-Tiemann reaction. Synthesis of phenolic aldehydes. Dichlorocarbene... 

Like other aromatic compounds, these five-membered heterocycles undergJ nitration, halogenation, sulfonation, and Friedel-Crafts acylation. They are mucji more reactive than benzene, and resemble the most reactive benzene derivatives (amines and phenols) in undergoing such reactions as the Reimer-Tiemann reaction, nitrosation, and coupling with diazonium salts. 

M.E. Jung and co-workers have developed a synthesis of selectively protected L-Dopa derivatives from L-tyrosine via a Reimer-Tiemann reaction followed by the modified Dakin oxidation. The formyl group introduced by the Reimer-Tlemann reaction had to be converted to the corresponding phenol. After trying many sets of conditions, the Syper process was chosen, which uses arylselenium compounds as activators for the oxidation. Treatment of the aromatic aldehyde with 2.5 equivalents of 30% hydrogen peroxide in the presence of 4% diphenyl diselenide in dichloromethane for 18h gave the aryl formate in excellent yield. This ester was cleaved by treatment with methanolic ammonia for 1h to afford the desired phenol in good yield. 

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