[76-03-9] · C2HCl3O2 · Trichloroacetic Acid · (MW 163.38)
(strong acid catalyst used in diazotization reactions and porphyrin syntheses; dichlorocarbene precursor)
Alternate Name: TCA.
Physical Data: mp 57-58 °C; bp 196-197 °C; d 1.629 g cm-3.
Solubility: sol alcohol, ether, water.
Form Supplied in: white crystals, widely available.
Handling, Storage, and Precautions: very caustic; should only be handled in a fume hood. Rubber gloves should be worn when handling this reagent. Extremely destructive to mucous membranes and tissues of upper respiratory tract, eyes, skin. Keep away from strong bases.
Trichloroacetic acid is used as a catalyst in the diazotization of amines by nitrites (eq 1). In this reaction, strong mineral acids (Hydrochloric Acid, Sulfuric Acid) give unsatisfactory results, as does Acetic Acid. Other catalysts used for this reaction are perfluorobutyric acid and Trifluoroacetic Acid.
The use of TCA as a catalyst allows the use of aldehydes with acid labile groups, such as acetals, in the synthesis of porphyrins (eq 2). This method is a convenient alternative to other methods available, which may not be as tolerant of other functionalities in the aldehydes.
Along with various other acids and bases, TCA catalyzes the condensation of silanols with alkoxysilanes (eq 3). This catalysis is believed to be bifunctional, with the acidic proton of TCA coordinating to the oxygen of the alkoxy silane, while the carbonyl oxygen coordinates to the proton of the silanol.
In the presence of strong base, TCA, as well as its esters and salts, reacts with alkenes to give 1,1-dichlorocyclopropanes (eq 4).4 The reaction of base with TCA eliminates CO2, leaving a trichloromethyl anion. This anion loses chloride ion to give dichlorocarbene, which subsequently reacts with the alkene to give the substituted cyclopropane. Dihalocarbenes from other sources undergo analogous reactions. The 1,1-dichlorocyclopropanes formed are subject to rearrangement, as shown by the reaction of norbornene with Ethyl Trichloroacetate (eq 5).5
TCA can be used to effect the Michael addition of trichloromethyl anion into alkenes and aromatic systems with strong electron-withdrawing groups attached, rather than forming 1,1-dichlorocyclopropanes (eqs 6-8).6 TCA can also react with carbonyls to give 1-(trichloromethyl)-substituted alcohols (eq 9).7
Enamines react with TCA to give trichloromethyl derivatives, which are somewhat unstable (eq 10).8 These rearrange to give a-chloroamides, via aziridinium salts. The trichloromethyl derivatives are generated by addition of the trichloromethyl anion to a carbocation formed by protonation of the enamine. Imines undergo a similar reaction.9
Primary aryl amines react via a dichlorocarbene formed from the decomposition of Sodium Trichloroacetate to yield isocyanates (eq 11).10
2-Alkoxybenzothiazolium salts of optically active alcohols, formed in situ by the reaction of 2-fluorobenzothiazolium with the appropriate alcohol, react with TCA to give the corresponding esters of trichloroacetate, which then undergo saponification to give back the optically active alcohols with inverted configuration (eq 12).11
Andrew K. Jones & Timothy E. Wilson
Emory University, Atlanta, GA, USA