224
S.A. Lermontov et al. / Journal of Fluorine Chemistry 121 (2003) 223–225
Scheme 1.
Table 1
2.1. Hexafluoroisopropanol
Hexafluoroacetone (HFA) reduction by high-temperature alcohols
Entry
R
HFA:ROH
mol)
T (8C/6 h)
HFIP
In a typical experiment, an autoclave filled with 5 ml of
the mixture containing HFAꢀ1.5 H O and i-PrOH in
(
Yield (%)
2
1
:10 mol ratio was heated in a furnace equipped with a
1
2
3
4
5
6
7
8
9
Me
Me
Et
1:10
1:10
1:10
1:10
1:10
1:10
1:10
1:10
1:1.5
1:1.5
1:1
180
220
180
180
180
200
220
240
220
240
210
0
30
10
43
42
73
86
96
75
88
65
device for automated temperature maintenance and the
temperature and pressure inside the autoclave were mon-
itored during heating. After the end of heating, the autoclave
i-Pr
2-Bu
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
was cooled and the reaction mixture was analyzed by 19
F
NMR. The HFA to HFIP ratio was determined by integration
thus giving the yield of the product (in a special experiment
it was shown that both HFA and HFIP do not loose CF3-
groups under reaction conditions). HFIP can be isolated as a
pure substance by distillation of the reaction mixture from
concentrated H SO . The (bp: 56–58 8C) H and 19F NMR
1
1
0
1
a
a
1
Nonaqueous HFA–i-PrOH compound [12] was used.
2
4
spectra coincide with those of a commercial sample.
A mixture of free trifluorolactic acid and its methyl and
2.2. Trifluorolactic acid
isopropyl esters is obtained as a result of transesterification;
further, this mixture can be easily converted to a pure acid by
hydrolysis.
Both compounds (HFA and MTP) are more active in this
reaction than the non-fluorinated ketones and aldehydes
investigated by Bagnell and Strauss [8] and substantially
shorter reaction times and smaller substrate: alcohol ratios
are required. This may be due to a greater ‘oxidative’
potential of fluorinated carbonyl compounds compared with
non-fluorinated analogues.
A solution of 7.8 g (0.05 mol) of MTP in 10 ml of i-PrOH
was heated at 250 8C during 6 h in an autoclave. After
cooling the reaction mixture was analyzed by 19F NMR
revealing three doublets (96% overall content by integra-
tion) which were attributed to CF CH(OH)COOR (R ¼ H,
3
Me and i-Pr). The reaction mixture was poured into 100 ml
of 2 M HCl and the solution was refluxed during 6 h. The
mixture was made alkaline by 5 M KOH (pH 12), extracted
byCHCl andEt OandacidifiedtopH1byconcentratedHCl.
3
2
The reaction mechanism undoubtedly includes formation
of an alcohol-HFA compound [12] and a reversible hydride
transfer, which is accelerated by high-temperature and hence
does not need a catalyst (Scheme 1).
It may be concluded that heating with secondary alcohols
can be a convenient method of MPV reduction of fluorinated
carbonyl compounds.
The acidified solution was exracted by Et O (4 ꢁ 20 ml),
2
combined extracts were dried over Na SO , all volatiles were
2 4
evaporated on a rotary evaporator and the residual oil was
dried by high-vacuum pumping giving 3 g (41%) of tri-
1
fluorolactic acid as a waxy solid. H NMR (d DMF): 4.9
7
(quartet, JHꢂF ¼ 7:6 Hz, 1H), 8.1 (broad s, 2H). 19F NMR:
3
3
1
1.4 (d, JFꢂH ¼ 7:9 Hz). The H NMR (CDCl –CD OD): 4.6
3
3
(
quartet, 1H), 5.15 (s, 2H) [10].
2
. Experimental
Acknowledgements
1H and 19F NMR spectra were recorded on a Bruker DPX-
00 spectrometer. Chemical shifts are referred to the exter-
nal standards Me Si and CF COOH, respectively. Hexa-
2
This work was supported by the Russian Foundation of
Basic Research, Grants # 03-03-32921 and 00-03-32846.
4
3
fluoroacetone sesquihydrate (HFAꢀ1.5 H O) and the methyl
2
ester of trifluoropyruvic acid MTP (both of 98% purity) were
produced by Unisyntez Ltd., Russia. Reactions were carried
out in a stainless steel 40 ml autoclave equipped with a
pocket for a thermocouple and a D-60 tensometric sensor for
precision pressure monitoring.
References
[
1] C.F. de Graauw, J.A. Peters, H. van Bekkum, J. Huskens, Synthesis
(1994) 1007–1017.