(p-Methoxybenzyloxy)methyl Chloride1

[88023-78-3]  · C9H11ClO2  · (p-Methoxybenzyloxy)methyl Chloride  · (MW 186.65)

(protection of alcohols;1 one-carbon synthon4)

Alternate Name: PMBM-Cl; 4-methoxybenzyl chloromethyl ether.

Physical Data: bp 66-67 °C/0.01 mmHg.

Preparative Method: easily prepared from the MTM ether of p-methoxybenzyl alcohol by treatment with Sulfuryl Chloride in CH2Cl2 at -78 °C followed by solvent evaporation and distillation.

Handling, Storage, and Precautions: decomposes upon storage1 but can be stored in the freezer for at least 3 days.2

Alcohol Protection.

The PMBM group was developed as an alcohol protecting group for protection of the allylic alcohol in the indole (1) when other groups were found not to be suitable. The PMBM group is readily introduced (PMBM-Cl, Diisopropylethylamine, CH2Cl2, rt, 5-30 h) on to a variety of structural types, as illustrated in Table 1. PMBM-Cl has also been used to trap alkoxides directly (eq 1).3

Deprotection is accomplished oxidatively with 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone, but conditions used for the deprotection of the p-methoxybenzyl group may also be suitable. It may also be cleaved by a simple hydrolysis with 3:1 THF/6 M HCl at 50 °C.

One-Carbon Synthon.

The preparation of 4-methoxybenzyloxymethyllithium from PMBM-Cl proceeds smoothly and is used in a reaction with crotonaldehyde to form a differentially protected diol derivative (eq 2).4

Related Reagents.

p-Methoxybenzyl Chloride; 4-Methoxybenzyl 2,2,2-Trichloroacetimidate.

1. Benneche, T.; Strande, P.; Undheim, K. S 1983, 762.
2. Kozikowski, A. P.; Wu, J.-P. TL 1987, 28, 5125.
3. Marshall, J. A.; Gung, W. Y. TL 1989, 30, 7349.
4. Booker-Milburn, K. I.; Heffernan, G. D.; Parsons, P. J. CC 1992, 350.

Peter G. M. Wuts

Upjohn Co., Kalamazoo, MI, USA

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