Alkyl methyl carbonates, phenol reactions

TABLE 4.8 Reactions of Phenol with Different Alkyl Methyl Carbonates"... 

Aryl ethers. Phenols are converted into methyl ethers by reaction with 1 in the presence of potassium carbonate and 18-crown-6 at 150°. The reaction involves liberation of chloroform and carbon dioxide (equation 1). If the reaction is conducted in the presence of an alkyl halide, alkyl aryl ethers are formed in generally good yield (equation 11). 

The palladium(0)-catalyzed asymmetric O-allylation of phenols has been described using five-, six- and seven-membered ring allylic carbonates and acyclic allylic carbonates (eq 9). The products from these reactions were subjected to a Claisen rearrangement to provide C-alkylated phenols. A study of various ligands for the reaction of phenol with 2-cyclohexenyl-l-methyl carbonate clearly showed that the Trost ligand is superior. ... 

The products of the asymmetric alkylation have been used as key building blocks in syntheses of morphanes, phyllanthocin, and periplanone B natural products. In the case of the synthesis of the morphane skeleton, a phenolic nucleophile was reacted with cyclohexenyl methyl carbonate and the resulting ether was subjected to a europium-induced Claisen rearrangement followed by an intramolecular aldehyde-ene reaction to generate the key tricyclic intermediate. Scheme 27 [56]. 

Deprotonation of phenol (P20.2) gives an anion which is equivalent to the enolate anion of cyclohexadienone (P20.3). This can be alkylated on carbon, rather than oxygen, if the reaction conditions are correct. The product ketone (P20.4) can be re-enolised to give o-cresol (P20.5) and the whole process repeated. After the addition of three methyl groups, the product ketone (P20.1) cannot enolise and so the alkylation process ceases (Figure S20). 

For carbon-carbon bond-formation purposes, S 2 nucleophilic substitutions are frequently used. Simple S 2 nucleophilic substitution reactions are generally slower in aqueous conditions than in aprotic organic solvents. This has been attributed to the solvation of nucleophiles in water. As previously mentioned in Section 5.2, Breslow and co-workers have found that cosolvents such as ethanol increase the solubility of hydrophobic molecules in water and provide interesting results for nucleophilic substitutions (Scheme 6.1). In alkylations of phenoxide ions by benzylic chlorides, S/y2 substitutions can occur both at the phenoxide oxygen and at the ortho and para positions of the ring. In fact, carbon alkylation occurs in water but not in nonpolar organic solvents and it is observed only when the phenoxide has at least one methyl substituent ortho, meta, or para). The effects of phenol substituents and of cosolvents on the rates of the competing alkylation processes... 

Unsubstituted cycloamyloses have been used to catalyze a number of reactions in addition to acyl group transfer. Brass and Bender (8) showed that cycloamyloses promoted phenol release from diphenyl and bis(p-nitro-phenyl) carbonates and from diphenyl and bis(m-nitrophenyl)methyl phos-phonates. Breslow and Campbell (10,11) showed that the reaction of anisole with HOCL in aqueous solution is catalyzed by cyclohexaamylose and cycloheptaamylose. Anisole is bound by the cyclodextrins and is chlorinated exclusively in the para position while bound. Cycloheptaamylose has been used to promote regiospecific alkylation followed by the highly selective oxidation shown in reaction (3) (95). In addition cycloheptaamylose effec-... 

A recent example of zeolite-catalyzed esterification involving biochemicals is the reaction of aminoacids with methanol. For instance, L-phenylalanine was converted to its methyl ester over H-USY at 130°C. However, the chiral carbon atom was racemized to a considerable extent, yielding an eventual ee of 52% (27). In the reaction of a, (3-unsaturated acids with phenols, the esterification over H-Beta is followed by an alkylation of the aromatic ring for instance resorcinol and acrylic acid react to form 7-hydroxy-3,4-dihydrocoumarin (28). 

The Williamson reaction, discovered in 1850, is still the best general method for the preparation of unsymmetrical or symmetrical ethers.The reaction can also be carried out with aromatic R, although C-alkylation is sometimes a side reaction (see p. 515). The normal method involves treatment of the halide with alkoxide or aroxide ion prepared from an alcohol or phenol, although methylation using dimethyl carbonate has been reported. It is also possible to mix the halide and alcohol or phenol directly with CS2CO3 in acetonitrile, or with solid KOH in Me2SO. The reaction can also be carried out in a dry medium,on zeolite-or neat or in solvents using microwave irradiation. Williamson ether synthesis in ionic liquids has also been reported. The reaction is not successful for tertiary R (because of elimination), and low yields are often obtained with secondary R. Mono-ethers can be formed from diols and alkyl halides. Many other... 

Phenol readily couples with diazonium salts to yield coloured compounds. The latter can be nsed for the photometric detection of phenol as in the case of diazotized 4-nitroaniline. Sahcylic acid (2-hydroxybenzoic acid) can be prodnced by the Kolbe-Schmitt reaction (stndied by the density functional method ) from sodinm phenolate and carbon dioxide, whereas potassium phenolate gives the para compound. Alkylation and acylation of phenol can be carried out with aluminium chloride as catalyst methyl groups can also be introduced by the Mannich reaction. Diaryl ethers can only be produced under extreme conditions. 

The classical Kolbe-Schmidt reaction treats alkali metal phenoxides and carbon dioxide at higher than atmospheric pressure, giving salicylic acid. Hirao and Kato developed several modifications for industrial production ". Recently, phenol phosphate was enzymatically carboxylated, giving p-hydroxybenzoic acid ". As for related reactions, Sartori and coworkers conducted o-carbamoylation of aluminum or boron phenoxides with alkyl isocyanate ", and Adachi and Sugasawa o-cyanated phenols using methyl thioisocyanate in the presence of BCI3 (equation 54). ... 

---