3.3.3- Trifluoropropionic acid

CHLORO-2,2,3-TRIFLUOROPROPIONIC ACID (Propionic acid, 3-chloro-2,2,3-trifluoro-)... 

Chloro-2,2,3-trifluoropropionic acid has been prepared by permanganate oxidation of 3-chloro-2,2,3-trifluoropropanol which is one of the telomerization products of chlorotrifluoroethylene with methanol. The present procedure is a modification of one reported earlier and is undoubtedly the method of choice for making propionic acids containing 2 fluorine atoms, i.e., 2,2,3,3-tetrafluoropropionic acid, 3,3-dichloro-2,2-difluoropropionic acid, and 3-bromo-2,2,3-trifluoropropionic acid. When preparing 2,2,3,3-tetrafluoropropionic acid from tetrafluoroethylene, it is desirable to use an additional 50 ml. of acetonitrile and externally applied heat to initiate the reaction. 

Chloro-2,2,3-trifluoropropionamide as by-product in synthesis of 3-chloro-2,2,3-trifluoropropionic acid, 40,12... 

The Wolff rearrangement is the third step of the Amdt-Eistert homologation of carboxylic acids. Figure 14.27 picks up an example that was discussed in connection with Figure 8.13, that is, the homologation of trifluoroacetic acid to trifluoropropionic acid. The first step of the Amdt-Eistert synthesis consists of the activation of the carboxylic acid via the acid chloride. The Cj elongation to an a-diazoketone occurs in the second step. 

A two-phase liq. mixture of NaCN, water, and acetonitrile shaken with cooling at 75-80° under 2.7 atm. chlorotrifluoroethylene until absorption of the latter ceases after ca. 1 hr., then poured slowly into aq. H2SO4 crude 3-chloro-2,2,3-trifluoropropionic acid. Y 76-79%. F. e. s. D. G. England and L. R. Melby, Org. Synth. 40, 11 (1960). 

W-(Methoxycarbonyl)triphenylphosphine imide reacts with methyl trifluoro-pyruvate to form methyl A -methoxycarbonyl 2 immo-3,3,3 trifluoropropionate m 95% yield This convenient building block easily adds nucleophiles such as Gngnard reagents without competing side reactions at the ester group to form trifluoromethylated amino acids [J.S] (equation 31)... 

The use of a silyl triflate and triethylamine to carry out the Ireland-Claiscn rearrangement was successfully employed by Nakai and co-workers60 in the early 1980s to convert allylic 3,3,3-trifluoropropionates 17 into 2-(trifluoromethyl)alk-4-enoic acids 18 (Table 22). The low dia-stereoselectivily in the rearrangement of 17b was attributed to the mixture of (E)- and (Z)-l-... 

Table 22. Synthesis of 2-(Trifluoromcthyl)alk-4-enoic Acids 18 by the Ireland-Claisen Rearrangement of Allylic 3,3.3-Trifluoropropionates I760...

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