P Methoxybenzyl Chloride

Substitution of a 2-pyridyl residue for the phenyl attached rectly to nitrogen affords a series of potent antihistamines, eparation of these compounds, too, is accomplished by a series alkylation reactions. It is further probable that the order the reaction can be readily interchanged. Thus, alkylation 2-aminopyridine with the chloroethyldimethylamine side chain ads to the diamine, 59. Alkylation with benzyl chloride af-rds tripelenamine (60) reaction with p-methoxybenzyl chloride ads to pyrilamine (61), °... 

Aromatic rings containing more than one hetero atom also yield active antihistamines. Alkylation of 2-aminopyrimidine (6S) with p-methoxybenzyl chloride gives the corresponding secondary amine (66). Alkylation with the usual chloroamine affords thonzylamine (67), Application of the same sequence to 2-aminothiazole (68) affords zolamine (70). ... 

Trimethyl phosphite (12.4 g, 0.1 mol) and p-methoxybenzyl chloride (15.6 g, 0.1 mol) were heated at reflux under a nitrogen atmosphere for 20 h. The residue was vacuum distilled (141°C/0.45 torr) to give the pure dimethyl (4-methoxybenzyl)phosphonate (12.6 g, 59%) as an oil, which exhibited spectra in accord with the proposed structure. 

Several 1-benzylisoquinoline alkaloids have been synthesized utilizing the above reaction sequence. For example, takatonine (34) has been obtained from Reissert compound 27 via alkylation with p-methoxybenzyl chloride and subsequent hydrolysis and quatemarization with methyl iodide 17). Similarly, es-cholamine (37) has been prepared from A-benzoyl-l-cyano-6,7-meth-ylenedioxy-1,2-dihydroisoquinoline (28) and 3,4-methylenedioxybenzyl chloride (77) as shown in Scheme 6. 

Raaen et al. (1974) have interpreted 12C/14C kinetic isotope effects as evidence against the ion pair mechanism they also dispute an alternative interpretation by Graczyk and Taylor (1974), who used 3 5 Cl/3 7 Cl isotope effects in a study of the hydrolysis of p-methoxybenzyl chloride. 

Access to derivatives with protecting groups other than benzyl was also desired. Tri-O-acetyl-D-glucal (13) was deacetylated and benzylated with p-methoxybenzyl chloride to give 14. Cleavage of the olefin in 14 gave formate aldehyde 15. Hydrolysis of the formate ester led to lactol 16 and Wittig olefination then furnished the PMB protected olefin alcohol Id (Scheme 3). 

D-Galactal Acetal Benzene TBAB 80 p-Methoxybenzyl chloride — 70 0 182... 

Methyl /3-lactoside (71) Acetal Benzene TBAI 80 p-Methoxybenzyl chloride 0 3 70 0 192... 

The sodium alkoxides prepared from primary and secondary alcohols and sodium hydride in a mixture of THF and DMF or DMSO react with p-methoxy-benzyl chloride at room temperature to give the p-methoxybenzyl ethers in good yield. Use of THF alone is not so satisfactory. p-Methoxybenzyl chloride (nip -1 °C bp 117 C/L9 kPa) is moisture sensitive and deteriorates on standing so it should be freshly distilled in vacuo before use. In sluggish reactions, the rate can be increased by the addition of a catalytic amount of tetrabutylam-... 

PhenyT9-xanthenyl Phenylmercuric acetate 4-Methoxybenzyl (p-methoxybenzyl) p-Methoxybenzyl chloride p-Methoxybenzyloxymethyl p-Methoxybenzyl alcohol 2,2,5,7,8-Pentamethylchroman-6-sulfonyl Pentamethyldiethylenetriamine Pentamethylbenzenesulfonyl... 

Using this scheme with other diarylacetylenes, or with p-methoxybenzyl chloride instead of benzal chloride, the p-anisyldiphenyl- di-p-anisylphenyl- and tri-p-anisylcyclopropenyl ions could be prepared. Monophenylacetylene is also a suitable component for the reaction and diphenylcyclopropenyl bromide (7) has been synthesized... 

Methoxybenzo[c]phenanthrene, 81 p-Methoxybenzyl alcohol, 669 p-Methoxybenzyl chloride, 668,1088 P Methoxybenqil oyanlda, 1088... 

Carboxymethyl-l(2//)-phthalazinone (25) with p-methoxybenzyl chloride gave4-p-methoxybenzyloxycarbonylmethyl-l(2/i)-phthalazinone (25a) (substrate, Nal, Et3N, Me2NCHO synthonj., 20°C, 3 h 42%). ... 

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