Chloromethyl ether formation

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. 

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. 

The reactivity of the chloromethyl group is illustrated by the reaction of 2,5-dimethyl-3,4-dichloromethylthiophene (174) with water, which gives (175) Another example of ether formation, is the formation of (176) upon normal acidic workup of the reaction product from 2-thiophenemagnesium bromide and 2-thiophenaldehyde. With... 

Halide ions will also act as nucleophiles towards aldehydes under acid catalysis, but the resultant, for example, 1,1-hydroxychloro compound (35) is highly unstable, the equilibrium lying over in favour of starting material. With HC1 in solution in an alcohol, ROH, the equilibrium is more favourable, and 1,1-alkoxychloro compounds may be prepared, e.g. 1-chloro-l-methoxymethane (36, a-chloromethyl ether ) from CH20 and MeOH (cf. acetal formation, p. 209), provided the reaction mixture is neutralised before isolation is attempted ... 

A Michaelis-Arbusov rearrangement followed by a Wittig-Horner reaction is involved in preparation of the distyrylbenzene derivative 11.37, as shown in Scheme 11.15. Precautions must be taken in the first stage to minimise formation of the carcinogenic by-product bis(chloromethyl) ether 11.16. The stilbene bis-ester 11.38 can be made by a similar procedure, or alternatively by the reaction of ethyl acrylate with 4,4 -dibromostilbene in the presence of a palladium-based catalyst (Scheme 11.16), a synthesis that yields the required trans form of the brightener. 

Serine has been prepared by the Strecker method from glycol-aldehyde 1 and from ethoxyacetaldehyde,2 3 by the condensation of ethyl formate with ethyl hippurate followed by reduction and hydrolysis,4 5 from the reaction product of chloromethyl ether with ethyl sodium phthalimidomalonate,6 and by amination of a-bromo-/3-methoxypropionic acid with subsequent demethyla-tion.7... 

Frankel, L.S., McCallum, K.S., and Collier, L. Formation ofbis(chloromethyl) ether from formaldehyde and hydrogen chloride, Environ. Scl. Technol, 8(4) 356-359, 1974. 

Travenius, S.Z.M. Formation and occurrence of bis(chloromethyl) ether and its prevention in the chemical industry, Scand. J. Work Environ. Health, 8(Suppl. 3) l-86, 1982. 

CAUTION Perform this preparation in a good hood because of the possible formation ofbis(chloromethyl)ether, as well as the pungent odors of salicylaldehyde, concentrated hydrochloric acid and acetic acid. 

The formation of 10 is an example of the addition of chloromethyl ethers to perfluorinated alkenes in the presence of potassium fluoride and a catalytic amount of tetrabutylammonium... 

An excellent means of protecting phenolic hydroxyl groups for reactions in alkaline media is by the formation of the methoxymethyl ether from the sodium salt of the phenol and chloromethyl ether, viz.,... 

It is also worthwhile to add that the versatility of the Wittig reaction suggested entirely new opportunities for the synthetic utilization of carbonyl compounds. Thus, the employment of methoxymethylenephosphorane 83 (easily prepared from chloromethyl ether) as the ylide component represents a standard protocol for the transformation of aldehydes or ketones into homologous aldehydes 84, via the intermediate formation of enol ether 84a. 

A very convenient hydroxymethylation process has been developed based on the Sml2-mediated Bar-bier-type reaction. Treatment of aldehydes or ketones with benzyl chloromethyl ether in the presence of Smh provides the alkoxymethylated products in good to excellent yields. Subsequent reductive cleavage of the benzyl ether provides hydroxymethylated products. Even ketones with a high propensity for enolization can be alkylated by this process in reasonable yields. The method was utilized by White and Soners as a key step in the synthesis of ( )-deoxystemodinone (equation 27). This particular ketone substrate resisted attack by many other nucleophilic reagents (such as methyllithium) owing to conpeti-tive enolate formation. 

Tetraglyme (2,5,8,11,14-pentaoxapentadecane) has been used in the hy-droxymethylation of aldehydes via addition of benzyl chloromethyl ether in the presence of Sml2. Addition of tetraglyme suppresses the competitive pinacol formation, presumably by a complex formation with Sml2 as evidenced by a purple color [25]. Tetraglyme has also been used as a cosolvent in an intramolecular Barbier reaction involving an iodoaldehyde and a THF solution of diiodosamar-ium [26]. 

CHLOROMETHYL ETHER (542-88-1) Forms explosive mixture with air (flash point <66°F/< 19°C). Contact with water causes decomposition and the formation of hydrogen chloride. Forms unstable peroxides. Contact with oxidizers, peroxides, sunlight may form shock-sensitive compounds. Attacks many plastics, coatings. Flow or agitation of substance may generate electrostatic charges due to low conductivity. 

Cyclopropyl ethers cyclopropeuyl ethers. Cyclopropyl ethers can be prepared in satisfactory yield by reaction of an alkene (excess) with chloromethyl ethers and LiTMP. The base eliminates HCl from the ether with formation of ROCH. 

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