Chloro methyl ether

The formaldehyde may be replaced by methylal CHjlOCH,), or by chloro-methyl ether CHjOCHjCl, produced from paraformaldehyde, hydrogen chloride and methyl alcohol ... 

This type of nucleoside includes numerous simple derivatives of heterocyclic compounds. Only a few examples are given. Condensation of the chloro-methyl ethers 1053 with silylated 5-fluorouracil gave the two mono- and one disubsituted derivatives 1054,1055, and 1056, respectively (86MI3). 

Chloromethylation is an efficient process but it has a serious drawback. Small amounts of the very carcinogenic (cancer-causing) bis(chloro-methyl)ether are formed in the reaction mixture so that the process has fallen out of favour. 

The use of alkyl bromides and chlorides, chloroacetone, and chloro-methyl ether mostly yields oily products in slow reactions. With phenacyl bromide the rate of the reaction depends on the kind and on the position of the substituents in the phenacyl bromide.110—I substituents favor the reaction. As a rule the initial thio compounds are readily regenerated from S-alkylthiopyrylium salts (49a and 50a) by bases. We already referred to this while discussing the synthesis of thiopyrones. 

A complete product study was reported on the reaction of bis(chloro-methyl) ether with a-bromoisobutyrate in the presence of zinc (557). The reaction of chloromethyl benzoate with a Reformatsky reagent RCH-(ZnBr)COOR gives PhC(OH)(OCH2CHRCOOR )(CHRCOOR ) (296). 

Typical examples of 2-chloroethoxycyclopropanes prepared from (2-chloroethyl) chloro-methyl ether, base and an alkene are collected in Table 39. 

SYNONYMS BCME, chloro-methyl-ether, sym-dichloro-dimethyl-ether, oxy-bis(chloromethane). 

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