Chloromethyl benzyl ether

Paul Sampson Kent State University, Kent, OH, USA 

Solubility sol THF, ether, dioxane, dichloromethane, chloroform, benzene, toluene, DMF, DMSO, and acetonitrile. 

Preparative Methods benzyl alcohol plus aqueous formaldehyde and hydrogen chloride gas - reaction of benzyl methyl ether with boron trichloride cleavage of benzyloxymethyl methyl sulfide with sulfuryl chloride.  

Handling, Storage, and Precautions stable indefinitely when kept dry but destroyed by water and other nucleophilic reagents. 

Alcohol Protecting Group. The foremost use for this reagent is as a protecting group for the alcohol functional group. This can be illustrated in a step utilized in the total synthesis of kijanolide (eq 1). An enantioselective synthesis of the taxol side chain used the benzyloxymethyl (BOM) ether for protection of an alcohol group (eq 2).  

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BENZYL CHLOROMETHYL ETHER (Ether, benzyl chloromethyl)... 

Several other alkylation reactions of benzyl chloromethyl ether have been reported using phosphorus compounds as nucleophiles. Hydrolysis and alcoholysis reactions of the reagent have been investigated along with the addition of the chloroether to propylene in the presence of zinc chloride. The alkylation of enamines with benzyl bromomethyl ether has been reported. ... 

Benzyl chloromethyl ether has been prepared from benzyl alcohol, aqueous formaldehyde solution, and hydrogen chloride. Gaseous formaldehyde and trioxane have also been used. This chloromethyl ether has also been prepared by the chlorination of benzyl methyl ether. The present procedure is based on the first method, but avoids the use of a large excess of formaldehyde and provides a considerably simplified isolation method. 

Alkylation, of acids, 50,61 with benzyl chloromethyl ether, 52,... 

Benzophenone, directed reaction with acetaldehyde, 50, 68 Benzoylacetone, from acetophenone and acetic anhydride, 51, 93 BENZYL CHLOROMETHYL ETHER, 52,16... 

Small samples may readily be distilled with little decomposition, while large samples decompose significantly during (list, nation. The undistilled material may be satisfactory for use in alkylation reactions without purification. The checkers have (bund that 200 g. quantities of the product can reprodticibly lie distilled at approximately 1 mm. The reported physical constants for benzyl chloromethyl ether are b.p. 96-98° (9.5 imn.)2, n n 1.5264-1.5292. i2... 

Caution must be used in handling benzyl chloromethyl ether since it is a mild lachrymator and reacts with water to form hydrogen chloride. 

The generation of ion pairs from NH-unsubstituted tetrazoles has also been performed using sodium salts and sodium hydroxide. Tetrazole alkylation with benzyl chloromethyl ether in tetrahydrofuran (THF) in the presence of sodium hexamethyldisilazane (NaHMDS) has been reported < 1995J(P 1) 1747, 1998SL528>. Regioisomers 240 and 241 formed under these conditions in comparable amounts (Scheme 24) <1998SL528>. 

Methoxy-2-tetralone was methylated by the Stork method to yield 337. The latter was treated with sodium hydride and benzyl chloromethyl ether to furnish compound 338 in 60% yield. Ketalization of 338 afforded the ketal 339 which was hydrogenated with palladium on calcium carbonate to give the alcohol 340 in a yield of 92%. The alcohol 340 was oxidized with chromium trioxide in pyridine to afford the aldehyde 341 in quantitative... 

Primary, secondary, and tertiary alcohols react with benzyl chloromethyl ether (BOMCI, bp 53-56 DC/0.Q7 kPa, HAZARD carcinogenic) in the presence of iPr2NEt to give the BOM ethers501 in good yield. If the reaction requires acceleration, some tetrabutylammonium iodide (10 mol%) may be added to the reaction mixture [Scheme 4.280],503... 

Hydroxymethylation of carbonyl compounds.3 Alkyl chloromethyl ethers react in the presence of Sml2 (2 equiv.) with ketones in THF to give adducts in 50-80% yield. The reaction with aldehydes is conducted in tetraethylene glycol dimethyl ether, which suppresses pinacol reduction. Hydroxymethylation of carbonyl compounds can be effected by use of benzyl chloromethyl ether followed by hydrogenolysis of the adduct. 

Chloromethylatioa. The reagent can be used for the piettaration of benzyl chloromethyl ether. ... 

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