[357-83-5] · C6H11ClF3N · (2-Chloro-1,1,2-trifluoroethyl)diethylamine · (MW 189.61)
(mild electrophilic fluorinating agent capable of nucleophilic substitution of hydroxyl group1-7 by fluorine)
Alternate Name: Yarovenko reagent.
Solubility: sol most aprotic organic solvents.
Preparative Method: from diethylamine and chlorotrifluoroethylene at -5 to -10 °C without solvent.
Purification: by distillation.
Handling, Storage, and Precautions: highly sensitive toward moisture (elimination of HF) and should be stored in tightly closed polyethylene vessels; reactions should be performed in thoroughly predried glass or quartz vessels; use in a fume hood.
The main application of the reagent (1) is in the preparation of alkyl or acyl flourides by the substitution reaction of hydroxyl groups (alcohols, carboxylic acids, and their salts) by fluorine (eqs 1 and 2).2
The fluorination of some cyclic secondary and especially tertiary alcohols may lead to the elimination of HF and alkene formation.3,4 Thioacids give acyl fluorides, rather than thioacyl fluorides.2
The fluorination can be performed using equimolar amounts or a slight excess of the reagent, either without solvent or in a solvent such as CH2Cl2, MeCN, Et2O, or THF. As a rule, the reactions are slightly exothermic or performed at rt. Neither t-amino groups nor alkoxycarbonyl groups prevent fluorination (eq 3).5
The reagent has been used extensively for the fluorination of steroids (eq 4).6-8
One paper9 describes the application of (1) to the fluorination of aromatic aldehydes to give difluoromethylene compounds (eq 5).
The mechanism of the fluorination includes nucleophilic substitution of the highly labile fluorine atom in the a-position to nitrogen to give the alkoxyamino intermediate which, in turn, undergoes SN2 reaction to give the corresponding fluoride and diethylamide of fluorochloroacetic acid (eq 6).
An analogous reagent (Et2NCF2CHFCF3 + Et2NCF=CFCF3; Ishikawa reagent) has been described.10
Nikolai S. Zefirov & Sergei A. Lermontov
Russian Academy of Science, Moscow, Russia