Benzyl chloride, condensation with phenol

Benzyl chloride reacts with benzene in the presence of a Lewis acid catalyst to give dipbenylmetbane [101 -81-5]. It undergoes self-condensation to form polymeric oils and soHds (21). With phenol, benzyl chloride produces a mixture of o- andp-her zylpbeno1. 

Reaction of dibenzylamine with ethylene oxide affords the amino alcohol, 82. Treatment of that product with thionyl chloride gives the a-sympathetic blocking agent, dibenamine (83). (Condensation of phenol with propylene chlorohydrin (84) gives the alcohol, 85. Reaction with thionyl chloride affords the chloride (86). Use of the halide to alkylate ethanolamine affords the secondary amine (87). Alkylation of this last with benzyl chloride... 

Condensation of phenol with propylene chlorohydrin gives an alcohol which upon treatment with thionyl chloride yields the corresponding chloride. This on alkylation with enthanolamine affords a secondary amine which on treatment with benzyl chloride followed by chlorination and lastly with hydrochloric acid yields the official compound. 

This reaction was initially studied by von Baeyer in 1872. It is an acid-catalyzed condensation of aromatic compounds with formaldehyde or formaldehyde derivatives. In normal conditions, the reactive benzene derivatives such as phenols and arylamines are applied to condense with formaldehyde however, a small number of less-reactive aromatics have also been used in this reaction, including benzene, toluene, benzyl chloride,biphenyl, iodobenzene, naphthalene, and mesitylene. Although no yields were given in the early studies, it is reasonable to obtain 70-80% yield for this type of reaction. Many other reactions have been developed to synthesize diarylmethanes, including Katritzky s benzotriazole method, Kochi s dealkylative coupling," Fukuzaw s 1,3-propandiol method, and the reduction method. In general, the condensation occurs at the /tflra-position of substituted aromatics. 

The second order nature of quaternization reactions in our system was confirmed by rate studies on model compounds. Although benzyl chloride is usually selected as the model for chloro-methylated polymers , we chose to synthesize a difunctional model that would be sensitive to neighboring group effects. Condensation of 4-chlorophenyl phenyl sulfone with the disodlum salt of bis-phenol-A yielded an excellent model for the polysulfone segment, Quantitative chloromethylation of with a chloromethyl methyl ether/ methyl acetate mixture in the presence of stannic chloride afforded the corresponding bischloromethyl adduct,... 

Synthesis of 51 commenced with racemic 7-hromotiyptophan methyl ester (52), a three-step process involving treatment with acyl chloride 53, Yonemitsu oxidation and degradation with HBr/AcOH afforded oxazole 54. Condensation of 54 with sulfonamide 55 gave phenol derivative 56, which underwent the key oxidative cycloaddition reaction mediated by PhI(OAc)2 to deliver the desired 57. A three-step functional group manipulation followed by acylation with 7-hydroxy trypt-amine 58 afforded diamide 59. A subsequent two-step benzylic oxidation and cyclodehydration sequence gave bis(oxazoyl)indole 60 (Scheme 8). 

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