Friedel-Crafts reaction phenol

By the Fries reaction. This is a variant of the Friedel-Craft reaction it consists in the conversion of an ester of a phenol to the corresponding o- and p-hydroxyketone, or a mixture of both, by treatment with anhydrous aluminium chloride ... 

As shown in the sixth entry of Table 24 4 C acylation of phenols is observed under the customary conditions of the Friedel-Crafts reaction (treatment with an acyl chloride or acid anhydride m the presence of aluminum chloride) In the absence of aluminum chloride however O acylation occurs instead... 

Aromatics containing electron releasing groups such as phenols, dim ethyl am in oben 2en e and indole are formylated by 2-ethoxy-l,3-dithiolane in the presence of boron trifluoroetherate, followed by hydrolysis (114). The preformed dithiolanium tetrafluoroborate also undergoes Friedel-Crafts reaction with aromatics such as dim ethyl am in oben 2en e and indole (115), and was used to generate dithiolanium derivatives (formyl precursors) from the enoltrimethylsilyl ether derivatives (116). 

Friedel-Crafts acylation using nittiles (other than HCN) and HCI is an extension of the Gattermann reaction, and is called the Houben-Hoesch reaction (120—122). These reactions give ketones and are usually appHcable to only activated aromatics, such as phenols and phenoHc ethers. The protonated nittile, ie, the nitrilium ion, acts as the electrophilic species in these reactions. Nonactivated ben2ene can also be acylated with the nittiles under superacidic conditions 95% trifluoromethanesulfonic acid containing 5% SbF (Hg > —18) (119). A dicationic diprotonated nittile intermediate was suggested for these reactions, based on the fact that the reactions do not proceed under less acidic conditions. The significance of dicationic superelectrophiles in Friedel-Crafts reactions has been discussed (123,124). 

Several methods are available to supplement the phenol alkylations described above. Primary alkylphenols can be produced using the more traditional Friedel-Crafts reaction. Thus an -butylphenol can be synthesized direcdy from a butyl haUde, phenol, and mild Lewis acid catalyst. Alternatively, butyryl chloride can be used to acylate phenol producing a butyrophenone. Reduction with hydrazine (a Wolff-Kishner reduction) generates butylphenol. 

Benzoyl chloride is an important benzoylating agent. In this use the benzoyl radical is introduced into alcohols, phenols, amines, and other compounds through the Friedel-Crafts reaction and the Schotten-Baumaim reaction. Other significant uses are in the production of benzoyl peroxide [94-56-0], benzophenone [119-61-9], and in derivatives employed in the fields of dyes, resins, perfumes, pharmaceuticals, and as polymerization catalysts. 

The general discussion (Section 4.02.1.4.1) on reactivity and orientation in azoles should be consulted as some of the conclusions reported therein are germane to this discussion. Pyrazole is less reactive towards electrophiles than pyrrole. As a neutral molecule it reacts as readily as benzene and, as an anion, as readily as phenol (diazo coupling, nitrosation, etc.). Pyrazole cations, formed in strong acidic media, show a pronounced deactivation (nitration, sulfonation, Friedel-Crafts reactions, etc.). For the same reasons quaternary pyrazolium salts normally do not react with electrophiles. 

Numerous preparative methods have been reported for these acids and their salts and ester derivatives.1 4 Dithiophosphoric acids are accessible from the reaction of phosphorus pentasulfide with alcohols or phenols (Equation 18). Dithiophosphinic acids can be prepared from thiophosphinic chlorides and sodium hydrosulfide (Equation 19), although the phenyl derivative is better prepared using a modified Friedel-Crafts reaction in which phosphorus pentasulfide is reacted with benzene in the presence of anhydrous aluminium trichloride (Equation 20). 

Reactions. -Hydroxybenzoic acid undergoes the typical reactions of the carboxyl and hydroxyl moieties. When heated above its melting point, it decomposes almost completely into phenol and carbon dioxide. It reacts with electrophilic reagents in the predicted manner and does not undergo the Friedel-Crafts reaction. Nitration, halogenation, and sulfonation afford the 3-substituted products. Heating -hydroxybenzoic acid with 8 IV-nitric acid results in a 95% yield of picric acid. In a similar fashion, treatment with chlorine water yields 2,4,6-trichlorophenol (50). 

Since the Friedel-Crafts reaction when applied to the phenol ethers yields the corresponding ketones far more easily than the same reaction applied to hydrocarbons (see Reaction XX. (6) (iv.)), it is noteworthy that the above reaction does not apply to the phenol ethers. To obtain aldehydes from them or from phenols, a modified method must be used (see pp. 104, 106). 

The phenol 44 can obviously be made by a Friedel-Crafts reaction and the amine 45 by reduction of the nitro group in 46 as well as of the benzene ring. Since OH and OEt are both o, p-directing, the syntheses are simple.9... 

As industrial relevant Friedel-Crafts reaction, the synthesis of Bisphenol-F, a material for epoxy resin, from phenol and formaldehyde was chosen [57]. This reaction involves formation of higher order condensates such as tris-phenols. To minimize the latter, the molar ratio of phenol to formaldehyde is set to a very high value (30-40), which is more than 15 times larger than the amount theoretically necessary. Three types of micromixers were used. These are a T-shaped mixer with 500 pm inner diameter, a multilaminating interdigital micromixer with 40 pm channels and a so-called self-made K-M micromixer with center collision mixing. 

We started this chapter by comparing phenols with enols (Ph-enol is the phenyl enol) and now we return to them and look at electrophilic substitution in full detail. You will find that the reaction is much easier than it was with benzene itself because phenols are like enols and the same reactions (bromination, nitration, sulfonations, and Friedel-Crafts reactions) occur more easily. There is a new question too the positions round the phenol ring are no longer equivalent—where does substitution take place ... 

We shall return to reactions of phenols and phenyl ethers when we consider directing effects in electrophilic aromatic substitution in other reactions and in Friedel-Crafts reactions in particular. 

Alkylation of aryl halides (method 76) and phenols (method 106) is discussed elsewhere as is the application of the Friedel-Crafts reaction to the synthesis of ketones (method 178) and carboxylic acids (method 273)-Nitro and alkoxy groups also have been present on the aromatic nucleus during alkylations. ... 

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