Synthesis of chloromethyl ethers from halogenated alcohols and corresponding fluoromethyl ethers

The reactivity of three halogenated alcohols 1,1,1,3,3,3-hexafluoro-2-propanol (1a), 2,2,2-trifluoroethanol(1b) and 2-chloroethanol (1c) in chloromethylation reaction with 1,3,5-trioxane and aluminum trichloride underdifferent conditions were investigated. the chloromethylated products (cf3)2choch2cl (2a) and cf3ch2och2cl(2b) were subjected to the nucleophilic substitution reaction by kf under single- and two-phase conditions. it hasbeen found out that both chloromethylation and fluorination reactions are highly dependent on the nature of r instarting roh. decreasing the number of halogen atoms in roh gradually shifts chloromethylation to acetalizationreaction such that in the case of 1a chloromethyl ether 2a is slowly and quantitatively produced while 1c results in theformation of the corresponding acetal as the major product in a fast kinetic reaction. accordingly, chloromethylationof the less strically hindered alcohols with higher pka, produces less chloromethylatied product under the alcl3/trioxane reaction condition. the nucleophilic fluorination of 2a is completed within 2h under reflux in polyethyleneglycol while negligible progress was detected under two-phase condition in ch2cl2/h2o. on the other hand, thenucleophilic fluorination kinetic of 2b was very slow and, thus, the corresponding fluoromethyl ether was preparedin 10 and 6% yields under the same single- and two-phase conditions, respectively.