M. Inoue et al. / Journal of Fluorine Chemistry 167 (2014) 135–138
137
Table 2
Synthesis of trifluoropropionic acid derivatives from
3. Conclusion
7
using various bases.
base (3.3 eq.)
Br
Br
In this paper, we described the simple and facile synthesis of
ethyl 3,3,3-trifluoropropionate (1) from commercially available 2-
bromo-3,3,3-trifluoropropene (2). Bromination of 2 with Br2 gave
2,2,3-tribromo-1,1,1-trifluoropropane (7) and the resulting tri-
bromide 7 was allowed to react with 3 equiv. of KOEt, giving 1 in
60% overall yield in 2 steps. We regarded this one pot sequence
involved an ethoxide induced elimination-substitution-elimina-
tion-addition pathway (path a) and/or an ethoxide induced
elimination-elimination-addition-substitution pathway (path b).
Br
CF3
CF3
COR
solvent (0.7 M),
15 min;
.
HCl aq.
7
1: R = OEt
11: R = OBut
12: R = NH2
13: R = OH
Entry
Base
Solvent
Temperature
Yield
(%)a
(8C)
1
2
3
4
5
6
7
KOEt (R = OEt)
KOEt (R = OEt)
KOEt (R = OEt)
KOEt (R = OEt)
KOBut (R = OBut)
NaNH2 (R = NH2)
KOAc (R = OH)
THF
THF
THF
Et2O
THF
THF
THF
20
0
75
4
40
20
20
20
20
62
(72)b
0
4. Experimental
4.1. General
0
0
a
All reactions involving air- and moisture-sensitive reagents
were carried out using oven-dried glassware and standard syringe-
septum cap techniques. Routine monitoring of reaction was carried
out and Low-resolution mass (MS) spectra were measured on a
Shimadzu GCMS-QP2010. All solvents and reagents were obtained
from commercial suppliers and were used without further
purification. Infrared (IR) spectral measurements were carried
out with a HORIBA FT-720 spectrometer. 1H, 13C, and 19F NMR
spectra were measured with a Bruker AVANCE III spectrometer.
Chemical shifts are expressed in parts per million (ppm) using
Determined by GC analysis.
b
Value in parentheses indicates isolated yield.
treatment of
7 with 1 equiv. of KOEt in THF produced
dibromopropene 8 concurrently with the formation of 1, we
thought our developed reaction began with elimination of HBr
from 7 and dibromide 8 is the first reaction intermediate.
There might be two possibilities to explain the second step
of the reaction: replacement of the bromine atom in 8 by
ethoxide ion to produce 9 [14] (path a) and/or elimination of
HBr from 8, followed by addition of EtOH to the resulting alkyne
14, affording alkene 15 (path b). Before quenching of the
reaction mixture with aq. HCl, the target compound 1 was not
observed by GC-Ms analysis and an unidentified product
(M+ = 184) was detected. After hydrolysis, this unidentified
compound disappeared with the formation of 1, which indicated
ketene diethyl acetal 16 (M+ = 184) may form as a precursor of
the targeted compound 1 during the reaction. We regarded
ketene diethyl acetal 16 was produced through elimination of
HBr from 9, followed by addition of EtOH to the resulting ynol
ether 10 and/or substitution of the bromine atom in 15 by
ethoxide anion.
tetramethylsilane (
d
= 0, 1H NMR) and C6F6
(
d
= À163.0, 19F NMR)
as standard substances. Multiplicities are indicated by s (singlet), t
(triplet), and q (quartet). 19F NMR spectra were recorded without
1H decoupling. High-resolution mass (HRMS) spectra were
measured on a JEOL MStation JMS-700 mass spectrometer.
4.2. Preparation of 2,2,3-tribromo-1,1,1-trifluoropropane (7)
To a stirred solution of 2-bromo-3,3,3-trifluoropropene (2)
(30.6 g, 0.175 mol) in CH2Cl2 (300 mL) was added dropwise
bromine (10.8 mL, 0.21 mol) at 0 8C and the resulting solution
was stirred at room temperature overnight. The resulting mixture
was quenched with 15% aq. Na2S2O3 (50 mL) and the aqueous layer
was extracted with CH2Cl2 (50 mL Â3). The extract was washed
with brine (40 mL), then dried over MgSO4. Concentration of the
solvent in vacuo afforded a residue, which was purified by
distillation to give 7 (49.1 g, 84%) as a colorless oil. bp. 79–81 8C
(80 mmHg). IR (neat): 1419, 1280, 1261, 1236, 1186, 1162, 1054,
Br
Br
933, 912, 894, 817, 775, 732, 705, 674, 651, 644 cmÀ1
.
1H NMR
Br
4.17 (s, 2H). 13C NMR (100 MHz, CDCl3):
d
CF3
Br
elimination
(path a)
(400 MHz, CDCl3):
d
7
+
Br
121.4 (q, JCF = 280 Hz, 1C), 57.08 (q, JCF = 33.6 Hz, 1C), 38.26 (s, 1C).
CF3
19F NMR (376 MHz, CDCl3):
calcd for C3H2Br3F3: 331.7659; found: 331.7664.
d
À74.4 (s, 3F). HRMS-EI: m/z [M]+
EtOK (3 eq.)
8
(path b)
substitution
Br
elimination
Br
4.3. Preparation of (EZ)-1,2-dibromo-1,1,1-trifluoropropene (8)
F3C
CF3
OEt
To a stirred solution of 2,2,3-tribromo-1,1,1-trifluoropropane (7)
(2.0 g, 6.0 mmol) in Et2O (50 mL) was added DBU (1.07 mL,
7.16 mmol) at room temperature and the resulting solution was
stirred for 1 h. The resulting mixture was quenched with aq. HCl
(1 M, 50 mL) and the organic phase was dried over MgSO4.
Concentration of the solvent in vacuo afforded a residue, which
was purified by distillation to give 8 (531 mg, 35%, E:Z = 1:2.7 by 1H
NMR) as a colorless oil. bp. 96 8C (760 mmHg). IR (neat): 1606, 1276,
CF3
14
9
elimination
addition
OEt
OEt
CF3
F3C
OEt
addition
substitution
OEt
16
Br
15
10
1141, 933, 919, 815, 782, 752, 717, 674, 609 cmÀ1
(400 MHz, CDCl3): 7.72(brq, J = 1.1 Hz, 1HforZ-isomer), 7.13(s, 1H
for E-isomer). 13C NMR (100 MHz, CDCl3):
120.3 (q, JCF = 271.3 Hz,
.
1H NMR
hydrolysis
CF3
d
d
CO2Et
1C for Z-isomer), 120.0 (q, JCF = 272.7 Hz, 1C for E-isomer), 119.4 (q,
JCF = 5.8 Hz, 1Cfor Z-isomer), 118.5(q, JCF = 37.6 Hz, 1Cfor Z-isomer),
111.4 (q, JCF = 3.1 Hz, 1C for E-isomer), 111.0 (q, JCF = 38.4 Hz, 1C for
1
Scheme 4. Plausible mechanism for the formation of 1.