Phenol, alkylation with allyl bromide

The combination of these compounds will generate the target compound through a three-step synthetic sequence. In the first step, illustrated below, phenol is alkylated with allyl bromide through an Sn2 mechanism. The mechanism for an SN2 reaction was presented in detail in Chapter 4. In this reaction it is important to... 

Monomer Synthesis. 4-Allyloxystyrene was prepared by the Wittig reaction of 4-allyloxybenzaldehyde and methyltriphenylphosphonium bromide, under basic conditions. The allyloxybenzaldehyde was prepared, in turn, by the alkylation of 4-hydroxybenzaldehyde with allyl bromide. This method, which provides high purity monomer in high overall yield, is outlined in Scheme 1 and has been previously described (2). Alternatively, the monomer may be prepared by the direct alkylation of p-vinylphenol with allyl bromide (8,9), although this method is less convenient due to the difficulties in synthesizing and storing the highly reactive vinyl phenol (10). 

The extent of C-alkylation as a side reaction in etherification varies about 1% of allyl 2-allylphenyl ether is formed when phenol is used in the acetone and potassium carbonate method with allyl bromide with cinnamyl bromide or 7,7-dimethylallyl bromide the extent of C-alkylar tion is greater.16 A complicated mixture of C- and O-alkylation products results from the treatment of phenol with 4-bromo-2-hexene and 4-chloro-2-hexene. 9 4-Hexenylresordnol has been obtained in about 40% yield from the reaction of l-bromo-2-hexene, resorcinol, and potassium carbonate in boiling acetone.99 An appreciable amount of C-alkylation occurs when 2,6-dimethyIphenol is treated with allyl bromide and sodium ethoxide in ethanol.70 Since, in general, the ampunt of C-alkylation is greatly increased by carrying out the alkylation on the sodium salt of the phenol in benzene,16 this method is unsuitable for the preparar tion of allyl aryl ethers. 

Phenols, such as e-nitrophenol (cf. Acetophenetidine), are alkylated by heating with alkyl chlorides in the presence of aqueous alkali. Methyl and ethyl bromides or iodides react very smoothly and, in spite of their cost, find application iii the field of dyes and medicinal products, e.g., pyramidone and antipyrine, for the preparation of simple and mixed ethers and for the alkylation of phenols and amines. Allyl bromide is employed for making diallylbarbituric acid (Dial). 

Unlike the acid-catalyzed ether cleavage reaction discussed in the previous section, which is general to all ethers, the Claisen rearrangement is specific to allyl aryl ethers, Ar—O—CH2CH = CH2. Treatment of a phenoxide ion with 3-bromopropene (allyl bromide) results in a Williamson ether synthesis and formation of an allyl aryl ether. Heating the allyl aryl ether to 200 to 250 °C then effects Claisen rearrangement, leading to an o-allylphenol. The net result is alkylation of the phenol in an ortho position. 

The solvent can also affect regioselectivity. Consider O- vs C-alkylation of phenoxide ion with allyl chloride or bromide. In water, with allyl chloride the O- to C-alkylation ratio is 49 41 with phenol as a solvent it is 22 78 with methanol, dimethylformamide, and dioxane 100% O-alkylation is achieved. The selective solvation of the more electronegative O by the more protic solvents perhaps leads to some C-alkylations. 

Conversion of phenols into their methyl or ethyl ethers by reaction with the corresponding alkyl sulphates in the presence of aqueous sodium hydroxide affords a method which avoids the use of the more expensive alkyl halides (e.g. the synthesis of methyl 2-naphthyl ether and veratraldehyde, Expt 6.111). Also included in Expt 6.111 is a general procedure for the alkylation of phenols under PTC conditions.38,39 The method is suitable for 2,6-dialkylphenols, naphthols and various functionally substituted phenols. The alkylating agents include dimethyl sulphate, diethyl sulphate, methyl iodide, allyl bromide, epichlorohy-drin, butyl bromide and benzyl chloride. 

Allylphenols and derivatives with substituents in the allyl group can, be prepared by direct C-alkylation of the sodium salt of the phenol in benzene solution.16 This method is not as good for the preparation of allylphenols themselves as the one involving preparation of the allyl ether followed by rearrangement, because a mixture of several products is obtained in C-alkylation. Thus the alkylation of p-cresol in benzene with sodium and allyl bromide yields 20% of allyl 4-methylphenyl ether, 8% of allyl 2-allyl-4-methylphenyl ether, 40% of 2-allyl-4-methyl-phenol, and 15% of 2,6-diallyl-4-methylphenol.16 The rearrangement of allyl 4-methylphenyl ether, however, yields 2-allyl-4-methylphenol in practically quantitative yield, and the ether is easily obtained. 

Preparation of Allyl Phenyl Ether, f A mixture of 188 g. of phenol, 242 g. of allyl bromide, 280 g. of finely ground calcined potassium carbonate, and 300 g. of acetone is refluxed on the steam bath for eight hours. A heavy predpitate of potassium bromide begins to form soon after the refluxing is started. After cooling, water is added the product is taken up in ether and washed twice with 10% aqueous sodium hydroxide solution. The ether solution is dried over potassium carbonate, and, after removal of the ether, the residue is distilled under diminished pressure. The yield is 230 g. (86%), b.p. 85°/19 mm., dll 0.9845. The residue is so small (6 g.) that the distillation might be omitted unless a very pure product is desired. About 1% of allyl 2-allylphenyl ether (a product of C-alkylation) is formed by this procedure. 

Electron-rich phenols react with isoprene in ionic liquids and with added Sc(OTf)3 to give 2,2-dimethylchromans <07SL3050>. Ionic liquids also promote the one-pot synthesis of 4-arylchromans from benzaldehydes, phenols and allyl bromide which involves sequential Barbier allylation, Friedel-Crafts alkylation and an intramolecular hydroalkoxylation <07SL1357>. 

Thiophene sulfonium salts have also been used for alkylation of phenols, thiophenols, and other nucleophiles (Equation 70) <2001T2871>. Ylides generated from THT and alkyl or allyl halides are known to react with aldehydes to form oxiranes. However, a modified procedure has been developed in which only a catalytic amount of THT is used for the preparation of vinyloxiranes from allyl bromides and aldehydes. In most of the cases, a m-/ra r-mixture of vinyloxiranes was obtained. Optically pure C2-symmetric /ra r-2,5-dimethyltetrahydrothiophene has also been used for the asymmetric version of this reaction, but the enantioselectivity was poor (25% ee) (Equation 71) <2003CC2074>. 

The study of phenol alkylation has a long history. Claisen and co-workers (178) showed that metal phenoxides react with active alkyl halides (e.g., allyl and benzyl bromides) in nonpolar solvents to give o-alkylphenols. Cyclohexa-dienones may be prepared in this way starting from 2,6-disubstituted phenols... 

In the next step of the dendrimer synthesis, treatment of the dichloromethylsilyl-capped product with allylmagnesium bromide provides eight terminal alkenes and provides the first-generation product. Subsequent cycles of hydrosilylation and alkylation provide the second- and third-generation dendrimers in similar fashion. The third-generation dendrimers were ultimately capped with phenols, pendant allyl- or alkoxy- groups, or phenylethylene units. ... 

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