Trifluoroacetylation of ketone O-vinyloximes

Article abstract of DOI:10.1023/A:1012363904621

Ketone oxime O-vinyl ethers having alkyl or phenyl radicals react with trifluoroacetic anhydride in ether in the presence of pyridine, yielding 43-54% of the corresponding ketone oxime O-(trans-4,4,4-trifluoro-3-oxo-1-butenyl) ethers with high stereoselec

Full text of DOI:10.1023/A:1012363904621

Russian Journal of Organic Chemistry, Vol. 37, No. 3, 2001, pp. 334 338. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 3, 2001,
pp. 362 366.
Original Russian Text Copyright
2001 by Vasil’tsov, Shmidt, Mikhaleva, Zaitsev, Tarasova, Afonin, Toryashinova, Il’icheva, Trofimov.
Trifluoroacetylation of Ketone O-Vinyloximes
A. M. Vasil’tsov, E. Yu. Shmidt, A. I. Mikhaleva, A. B. Zaitsev, O. A. Tarasova,
A. V. Afonin, D.-S. D. Toryashinova, L. N. Il’icheva, and B. A. Trofimov
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: bat@irioch.irk.ru
Received June 13, 2000
Abstract Ketone oxime O-vinyl ethers having alkyl or phenyl radicals react with trifluoroacetic anhydride
in ether in the presence of pyridine, yielding 43 54% of the corresponding ketone oxime O-(trans-4,4,4-tri-
fluoro-3-oxo-1-butenyl) ethers with high stereoselectivity.
Trifluoro(or trichloro)acetylation of vinyl ethers
with trifluoro(trichloro)acetic anhydride can be
regarded as electrophilic substitution at the vinyl
fluoroacetic anhydride. We also planned to find
conditions under which the reaction can be stopped
at the stage of formation of primary replacement
products. We have found that thoroughly dehydrated
-
carbon atom. As a rule, the reaction proceeds
smoothly under mild conditions and leads to forma- O-vinyloximes Ia Ie react with trifluoroacetic anhy-
tion of trans-trifluoro(trichloro)acetylvinyl ethers in
high yields. These products are valuable synthons for
preparation of potential biologically active hetero-
cyclic compounds, specifically of perhaloacyl pyran
derivatives [1 4].
Ketone O-vinyloximes, which have become acces-
sible in the recent time [5, 6], may also be regarded
as vinyl ethers. However, the double bond in these
compounds appears near the energy-rich ON group [6]
in which the basic nitrogen atom can also be attacked
by electrophile. The first attempt to effect trifluoro-
acetylation of acetone oxime O-vinyl ether (Ia)
resulted in formation of not only expected trifluoro-
acetyl derivative but also of product of its further
transformation, 5-hydroxy-5-trifluoromethyl-4,5-di-
hydro-1,2-oxazole (II) [7].
dride in dry diethyl ether in the presence of pyridine at
room temperature as readily as common vinyl ethers
do (the reaction conditions were almost identical to
those described in [1]). As a result, expected O-(trans-
4,4,4-trifluoro-3-oxo-1-butenyl)oximes IIIa IIIe were
isolated in 43 54% yield (Scheme 1). The yields,
physical properties, and elemental analyses of com-
pounds IIIa IIIe are given in Table 1, and Tables 2
and 3 contain their NMR and IR spectral parameters.
1
In the H NMR spectra of oximes IIIa IIIe the
3
coupling constant J(1-H, 2-H) was found to be
12.3 Hz. This value corresponds to trans-replacement
of hydrogen at the -carbon atom of the vinyl group
with formation of the trans isomers. Introduction of
a trifluoroacetyl group sharply changes 13C chemical
shifts of unsaturated fragments, as compared to initial
O-vinyloximes Ia Ie, indicating strong redistribution
of electron density. Signals from the - and -carbon
atoms shift downfield by 11 and 14 ppm, respec-
The goal of the present work was to get a deeper
insight into specific features of the reaction of ali-
phatic and aromatic ketone O-vinyloximes with tri-
Scheme 1.
1
2
1
2
1
2
1
2
1
2
R = R = Me (a); R = Me, R = i-Pr (b); R = Me, R = t-Bu (c); R = R = i-Pr (d); R = Me, R = Ph (e).
1
070-4280/01/3703-0334$25.00 2001 MAIK Nauka/Interperiodica

TRIFLUOROACETYLATION OF KETONE O-VINYLOXIMES
335
Table 1. Yields, boiling points, refractive indices, and elemental analyses of O-(trans-4,4,4-trifluoro-3-oxo-1-butenyl)-
oximes IIIa IIIe
Found, %
Calculated, %
Comp. Yield,
bp,
(p, mm)
C
2
0
n
Formula
D
no.
%
C
H
F
N
C
H
F
N
IIIa
IIIb
IIIc
IIId
IIIe
53
53
52
54
43
60 63 (2)
62 64 (2)
70 72 (2)
78 80 (3)
116 119 (2)
1.4410 42.99 4.56 28.67 7.20 C H F NO
2
43.08 4.13 29.21 7.18
48.43 5.42 25.54 6.28
50.63 5.95 24.03 5.90
52.59 6.42 22.69 5.57
56.04 3.93 22.16 5.45
7
8 3
1.4414 47.84 6.02 25.60 6.25 C H F NO
9
12 3
2
1.4411 50.65 6.02 23.73 5.80 C H F NO
1
0
14 3
2
2
2
1.4406 52.31 6.70 23.01 5.52 C H F NO
1
1 16 3
1.5286 56.26 4.27 22.37 5.72 C H F NO
1
2 10 3
tively. In the former case this shift directly results
from the substitution of hydrogen, and the downfield
shift of the -carbon signal reflects -acceptor effect
of the trifluoroacetyl fragment. The same factor is
responsible for the downfield shift of the C N signal
by 5 6 ppm (Table 2). In molecule IIIe the acceptor
effect of the trifluoroacetyl group also extends to the
ortho- and para-carbon atoms of the benzene ring:
the corresponding signals shift downfield by 1.2 and
The calculation results (Table 3) were fully consistent
with the experimental data, including both vibration
frequencies and band intensities.
The increased intensity and reduced frequency of
the C C bond vibrations in trifluoroacetyl derivatives
may be explained by p, -conjugation involving
double bonds and heteroatoms, for the molecule is
planar. Introduction of a bulky isopropyl or tert-butyl
group into the ketone fragment distorts the planar
structure, which results in splitting of the symmetric
bending vibration of methyl C H bonds. Therefore,
the IR spectra of compounds IIIb IIId contain
doublet absorption bands at 1385/1371, 1399/1370,
2
.2 ppm, respectively.
No thermal isomerization of the products about the
double C C bond was observed during vacuum
1
13
distillation (60 119 C). However, the H and
C
1
NMR spectra of IIIb contain two sets of signals from
the methyl and isopropyl groups, indicating the pres-
ence of E and Z isomers with respect to the C N
and 1388/1370 cm , respectively. In the IR spectrum
of trifluoroacetyl derivative IIIe, the monosubstituted
1
benzene ring is characterized by bands at 1766 cm
1
(overtone) and 692 and 761 cm 1 (out-of-plane
bending vibrations). Characteristic frequencies in the
regions 1600 1580 and 1500 1450 cm 1 are obscured
by the C C and C N bond vibrations. The results of
calculations of molecule IIIa show that IR absorption
in the region 892 905 cm 1 belongs to stretching
vibrations of the N O bond. According to published
bond. The H NMR data show that the isomer ratio
of product IIIb is the same as in the initial O-vinyl-
oxime Ib (E:Z = 7:1). In the other cases, i.e., with
unsymmetrically substituted compounds IIIc and IIIe,
no Z isomers were detected.
Trifluoroacetyl derivatives showed a quite different
absorption pattern in the IR regions 1590 1715 and
1
1
2
850 3100 cm , as compared with initial O-vinyl-
data [10], the HC CH vibration band at 960 cm ,
oximes I. All products IIIa IIIe are characterized by
which characterizes trans configuration of the double
bond, should have a high intensity. However, the band
at 972 cm 1 in the IR spectra of trifluoroacetyl deriva-
tives III is medium. The IR spectra of compounds
IIIa and IIIe are also characterized by low intensity
a very strong IR absorption band with its maximum
1
at 1595 1598 cm , (C C). The CF group gives
3
1
rise to symmetric bending vibration band at 1307 cm
and strong asymmetric vibration bands at 1195 and
1
(
at the background level) of stretching vibrations of
1
146 cm . The C N vibration frequency differs only
C H bonds in the substituents.
slightly from that observed for initial O-vinyloximes
1
Ia Ie [5, 6, 8]; it ranges from 1626 to 1652 cm ,
Trifluoroacetyl O-vinyloxime derivatives IIIa IIId
are light yellow liquids (compound IIIe is light red)
with a specific odor, which are soluble in most
organic solvents. Unlike initial O-vinyloximes I which
are capable of decomposing with explosion on heating
to 145 155 C [6], trifluoroacetyl derivatives IIIa IIIe
are more thermally stable (no explosions occurred
while working with these compounds). The low yields
depending on the substituent in the ketone fragment.
Carbonyl stretching vibrations appear as a doublet
1
band at 1712/1692 cm with unusually low intensity.
In order to assign IR bands more precisely, we have
calculated vibration frequencies of the three double
bonds in compound IIIa using Gaussian-98 program
[9] assuming equilibrium geometry (6-31G basis set).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 3 2001

3
36
VASIL’TSOV et al.
Table 2. 1H and 13C NMR spectra of O-(4,4,4-trifluoro-3-oxo-1-butenyl)oximes IIIa IIIea
1H NMR spectrum, , ppm
13C NMR spectrum,b C, ppm
Comp.
no.
1
-H 2-H
R1
R2
C O
C N
C
C
CF3
R1
R2
IIIa
8.21 6.18
2.00
2.02
180.36
163.90
(
170.44
166.91
97.80 116.53 21.47 16.73
(21.23) (15.63)
97.66 116.42 17.51 34.44, 19.36
(164.65) (152.61) (86.99) (11.82) (34.29, 19.62)
170.44 167.08 97.66 116.42 18.89 27.36, 18.89
(165.51) (152.57) (86.95) (15.14) (27.07, 18.95)
172.11 167.28 97.61 116.45 11.70 37.99, 27.21
166.00) (152.76) (86.92) (10.94) (37.36, 27.49)
176.69 167.04 96.97 116.05 31.27, 29.13, 18.51
(171.34) (152.87) (86.72)
157.26)b (152.32) (86.79)
E-IIIb 8.22 6.15
Z-IIIb 8.22 6.15
1.93 2.58 (CH), 180.20
.12 (2Me)
1.88 3.38 (CH), 180.20
167.08
1
1
.07 (2Me)
1.16 180.17
IIIc
IIId
8.23 6.15
8.23 6.13
1.95
(
3.07 2.58 (CH), 179.78
CH), 1.12 (2Me)
.17
(
1
20.27 (28.86, 19.12)
(31.46,
(
2Me)
21.06)
i
IIIe
8.33 6.30
2.40 7.68 (2-H), 180.12
162.93
166.90
98.33 116.45 13.91 133.85 C ,
p
7
.49 7.23
(157.13) (152.78) (88.11)
(13.21) 131.05 C ,
o
(3-H, 4-H)
128.79 C ,
m
1
(
1
1
1
26.81 C
i
135.86 C ,
p
29.26 C ,
o
26.32 C ,
m
28.42 C )
a
3
1
2
For all the compounds, J(1-H,2-H) = 12.3 Hz, J(C,F) = 290.6 Hz, J(C,F) = 35.1 Hz.
In parentheses are given the chemical shifts for the corresponding initial O-vinyloximes.
b
of products III, as compared to trifluoroacetyl deriva-
tives of common vinyl ethers [1], may be attributed
to side polymerization processes: Their distillation
resulted in formation of a considerable amount of tars.
Due to the presence of activated C C bond com-
pounds IIIa IIIe readily undergo hydrolysis to give
(II) (Scheme 2; see also [7]). This scheme is sup-
ported by the H NMR spectra of samples exposed to
1
atmospheric moisture (3 days, 18 20 C). The spectra
contained signals belonging to compounds III, di-
hydrooxazole II, intermediate 4,4,4-trifluoro-3-oxo-
butyraldehyde oxime (IV), and also ketones V. In
1
5
-hydroxy-5-trifluoromethyl-4,5-dihydro-1,2-oxazole
the H NMR spectrum of a mixture obtained by partial
Scheme 2.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 3 2001

TRIFLUOROACETYLATION OF KETONE O-VINYLOXIMES
337
1
Table 3. Absorption bands ( , cm ) in the IR spectra of O-(trans-4,4,4-trifluoro-3-oxo-1-butenyl)oximes IIIa IIIe
Comp.
no.
C O
C N
C C
CF3
HC CH
972 m
R1, R2
HC CH, R1, R2
IIIa
1711 s-m, 1691 m,
1652 m
1598 v.s 1195 v.s,
1433 m
1372 m
3089 w, 3000 w,
2970 w, 2927 w
a
b
1598a
1
1
680 m
1638 (116)
1146 v.s
700 (75)b
a
(880)b
IIIb
IIIc
1712 s-m
692 m
1643 m
1638 m
1594 v.s 1196 v.s,
1147 v.s
972 m
972 m
1469 m
1420 m
3093 w, 3052 w,
2975 s, 2938 m,
2879 m
1
1
1
385 m
371 m
1712 s-m
692 m
1597 v.s 1197 v.s
1146 v.s
1480 m
1465 m
2975 s, 2943 m,
2912 m, 2875 m
1
1
1
399 w
370 s-m
IIId
IIIe
1712 s-m
693 m
1642 m
1626 m
1593 v.s 1195 v.s
1146 v.s
971 m
985 m
1470 m
1388 m
3086 w, 3052 w,
2974 s, 2939 m,
2879 m
3059 m, 2930 w,
2855 v.w
1
1
370 m
1712 s-m
691 m
1592 v.s 1198 v.s
1145 v.s
761 s
692 s
1
a
Calculated frequency.
Relative intensity.
b
hydrolysis of oxime IIIe we observed a triplet at
.48 ppm ( CH) and a doublet at 3.51 ppm (CH2,
J = 5.68 Hz), which can be assigned to intermediate
IV; also, a singlet from the methyl protons of aceto-
phenone was present at 2.60 ppm. The absence of
signal from aldehyde proton of 4,4,4-trifluoro-3-oxo-
butyraldehyde (VI) in the downfield region of the
spectrum ( 9 10 ppm) suggests that the stages of
water addition and cyclization are much slower than
transoximation of ketone oxime VII with aldehyde VI
O-(trans-4,4,4-Trifluoro-3-oxo-1-butenyl)oximes
III (general procedure). A solution of 6.30 g
(30 mmol) of trifluoroacetic anhydride in 5 ml of
diethyl ether was added dropwise with stirring at
18 20 C to a solution of 10 mmol of appropriate
ketone O-vinyloxime I and 0.87 g (11 mmol) of
pyridine in 5 ml of diethyl ether. The time of addition
was 30 min. The mixture was then stirred for 2.5 h,
the solvent was distilled off, and the residue was
distilled in vacuo. In the synthesis of compounds
IIIb IIIe, pyridinium trifluoroacetate was preli-
minarily removed by flash chromatography on a dry
column charged with silica gel (5 40 m) containing
an LL254 luminescent indicator (the adsorbent was
calcined for 5 h at 140 C; eluent diethyl ether).
6
3
(
exchange of the oxime moiety between carbonyl
compounds VII and VI is well known [11]).
EXPERIMENTAL
The H and 13C NMR spectra were recorded on
1
a Bruker-400DPX instrument operating at 400.13 and
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