Chloromethyl ether

Synonyms BCME chloromethyl ether chloro(chloromethoxy)methane dichloro-methyl ether symmetrical dichloro-dimethyl ether dimethyl-1 -1dichloroether 

Toxicology, bis (Chloromethyl) ether (BCME) is a mucous membrane and respiratory irritant it is a recognized human carcinogen. 

In humans, concentrations of 3 ppm are reported to be distinctly irritating. A fatal case of accidental acute poisoning of a research 

A retrospective study of 136 BCME workers employed at least 5 years revealed 5 cases of lung cancer, which represented a ninefold increase in lung cancer risks 0.54 cases would have been expected to occur in the plant population. The predominant histologic type of carcinoma was small cell undifferentiated. Exposure ranged from 7.5 to 14 years, and the mean induction period was 15 years. In addition, abnormal sputum cytology was observed in 34% of 115 current workers with exposure to BCME for 5 or more years, as contrasted with 11 % in a control group. 

In another study, 6 cases of lung cancer occurred among 18 technical department workers, a group known to experience very high BCME exposure other cases of lung cancer were reported among 50 production workers. Oat cell carcinomas occurred in five of eight cases. 

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Cm.OROCARBONSANDCm.OROHYDROCARBONS - BENZYL Cm ORIDE, BENZAL Cm ORIDE AND BENZOTEICm.ORIDE] (Vol 6) Bis(chloromethyl) ether [542-88-1]... 

The hydroxyl groups can be alkylated in the usual manner. Hydroxyalkyl ethers may be prepared with alkylene oxides and chloromethyl ethers by reaction with formaldehyde and hydrogen chloride (86). The terminal chlorides can be easily converted to additional ether groups. 

The limitations of this reagent are several. It caimot be used to replace a single unactivated halogen atom with the exception of the chloromethyl ether (eq. 5) to form difluoromethyl fluoromethyl ether [461 -63-2]. It also caimot be used to replace a halogen attached to a carbon—carbon double bond. Fluorination of functional group compounds, eg, esters, sulfides, ketones, acids, and aldehydes, produces decomposition products caused by scission of the carbon chains. 

Under neutral or slightly alkaline conditions, only the unstable hemiformal (CH O—CH2OH, methoxymethan0I) is produced. Alpha-chloromethyl ether is synthesized from aqueous formaldehyde, methanol, and hydrogen chloride (54). However, under anhydrous conditions, a carcinogenic by-product, bis(chloromethyl)ether is also formed (55). 

Chloromethjlation Reactions. The introduction of the chloromethyl group to both aHphatic and aromatic compounds is carried out by reaction of paraformaldehyde [30525-89-4] and hydrogen chloride. This method is used for synthesizing methyl chloromethyl ether [107-30-2], benzyl chloride [100-44-7], and chloromethyl acetate. 

Ghloromethylation. The reactive intermediate, 1-chloromethylnaphthalene [86-52-2] has been produced by the reaction of naphthalene in glacial acetic acid and phosphoric acid with formaldehyde and hydrochloric acid. Heating of these ingredients at 80—85°C at 101.3 kPa (1 atm) with stirring for ca 6 h is required. The potential ha2ard of such chloromethylation reactions, which results from the possible production of small amounts of the powerhil carcinogen methyl chloromethyl ether [107-30-2J, has been reported (21). 

The typical acid catalysts used for novolak resins are sulfuric acid, sulfonic acid, oxaUc acid, or occasionally phosphoric acid. Hydrochloric acid, although once widely used, has been abandoned because of the possible formation of toxic chloromethyl ether by-products. The type of acid catalyst used and reaction conditions affect resin stmcture and properties. For example, oxaUc acid, used for resins chosen for electrical appHcations, decomposes into volatile by-products at elevated processing temperatures. OxaUc acid-cataly2ed novolaks contain small amounts (1—2% of the original formaldehyde) of ben2odioxanes formed by the cycli2ation and dehydration of the ben2yl alcohol hemiformal intermediates. 

Curing the treated fibers with ammonia chemically attaches the compound to the cloth. The corresponding sulfate has replaced much of the hydroxide because under certain conditions of manufacture or use the carcinogen bis(chloromethyl) ether may form. 

Alkylation involving formaldehyde in the presence of hydrogen chloride is known as chloromethylation (eq. 3). The reagent may be a mixture of formalin and hydrochloric acid, paraformaldehyde and hydrochloric acid, a chloromethyl ether, or a formal. Zinc chloride is commonly employed as a catalyst, although many other Lewis acids can be used. Chloromethylation of sahcyhc acids yields primarily the 5-substituted product 5-chlotomethylsahcyhc acid [10192-87-7] (4). 

Etherification. The reaction of alkyl haUdes with sugar polyols in the presence of aqueous alkaline reagents generally results in partial etherification. Thus, a tetraaHyl ether is formed on reaction of D-mannitol with aHyl bromide in the presence of 20% sodium hydroxide at 75°C (124). Treatment of this partial ether with metallic sodium to form an alcoholate, followed by reaction with additional aHyl bromide, leads to hexaaHyl D-mannitol (125). Complete methylation of D-mannitol occurs, however, by the action of dimethyl sulfate and sodium hydroxide (126). A mixture of tetra- and pentabutyloxymethyl ethers of D-mannitol results from the action of butyl chloromethyl ether (127). Completely substituted trimethylsilyl derivatives of polyols, distillable in vacuo, are prepared by interaction with trim ethyl chi oro s il an e in the presence of pyridine (128). Hexavinylmannitol is obtained from D-mannitol and acetylene at 25.31 MPa (250 atm) and 160°C (129). 

An 80% yield of benzyl chloride is obtained with sulfuryl chloride as chlorinating agent. Yields of >70% of benzyl chloride are obtained by the zinc chloride-catalyzed chloromethylation of benzene but formation of bis-chloromethyl ether presents a health hazard for this reaction pathway. 

This derivative has been prepared from an indole, the chloromethyl ether, and potassium hydride in 50% yield it is cleaved in 84% yield by potassium cyanide/ 18-crown-6 in refluxing acetonitrile/ ... 

Carcinogens Cancer-producing agents Skin Respiratory Bladder/urinary tract Liver Nasal Bone marrow Coal tar pitch dust crude anthracene dust mineral oil mist arsenic. Asbestos polycyclic aromatic hydrocarbons nickel ore arsenic bis-(chloromethyl) ether mustard gas. p-naphthylamine benzidine 4-am i nodi pheny lam ine. Vinyl chloride monomer. Mustard gas nickel ore. Benzene. 

Beryllium compounds (except aluminium beryllium silicates) Bis(chloromethyl)ether (BCME)... 

Bis(chloromethyl)ether [542-88-1] and chloromethyl methyl ether [107-30-2] (technical-grade)... 

Biphenyl ether bis (2-Chloromethyl) ether bis (Dimethylaminoethyl) ether Bromine... 

Bhmingham Metal Company Ltd., 207 Bis(2-chloroisopropyl) ether, 25 Bis(chloromethyl) ether, 25 Bis(chloromethyl) ketone, 25 Bis(2-EthyUiexyl) phthalate, 25 Bismuth and Bismuth Compounds, 25 Bismuth Institute, 256 Bismuth telluride, 26 Bisphenol-A, 26 Bithionol, 26 Bitmac Ltd., 207, 236 Bitoscanate, 26 Bitoumina SA, 167... 

Chlorobenzene Producers Association (CPA), 270 p-Chlorobenzotrichloride, 39 Chlorobenzotrifluorides, 39 Chlorobromomethane, 39 Chlorodifluorobromomethane, 39 Chlorodifluoroethane, 39 Chlorodifluoromethane, 39 Chlorodiphenyl, 39 Chloroethanol, 39 2-Chloroethyl vinyl ether, 39 Chlorofluorocarbons, 39 Chloroform, 40 Chloromethyl anilines, 40 Chloromethyl ether, 40 Chloromethyl methyl ether, 40 2-(4-Chloro-2-methylphenoxy) propionic acid, 40 Chloromethyl phenyl isocyanate, 40... 

The BOM group is introduced onto an indole with the chloromethyl ether and sodium hydride in 80-90% yield. It is cleaved in 92% yield by catalytic reduction followed by basic hydrolysis, or by CF3COOH, HBr or 6 M HCl at... 

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