Synthesis and properties of 2,2-dichlorovinyl trifluoromethyl ketone

Article abstract of DOI:10.1023/A:1012483314133

Highly reactive 2,2-dichlorovinyl trifluoromethyl ketone was synthesized. Its reactions with N,N-and N,S-nucleophiles gave 1,3-thiazine, pyrazole, and imidazole derivatives containing a trifluoromethyl substituent.

Full text of DOI:10.1023/A:1012483314133

Russian Journal of Organic Chemistry, Vol. 37, No. 5, 2001, pp. 644 648. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 5, 2001,
pp. 684 688.
Original Russian Text Copyright
2001 by Levkovskaya, Bozhenkov, Larina, Evstaf’eva, Mirskova.
Synthesis and Properties of 2,2-Dichlorovinyl
Trifluoromethyl Ketone
G. G. Levkovskaya, G. V. Bozhenkov, L. I. Larina,
I. T. Evstaf’eva, and A. N. Mirskova
Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: ggl@irioch.irk.ru
Received April 5, 2000
Abstract Highly reactive 2,2-dichlorovinyl trifluoromethyl ketone was synthesized. Its reactions with N,N-
and N,S-nucleophiles gave 1,3-thiazine, pyrazole, and imidazole derivatives containing a trifluoromethyl
substituent.
Compounds containing a trifluoromethyl group, chloride is stabilized through elimination of proton
especially those belonging to the heterocyclic series,
exhibit high biological activity. Some representatives
have found application as drugs and herbicides [1].
With the goal of obtaining heteroatomic and hetero-
cyclic compounds having a CF3 group we synthesized
previously unknown 2,2-dichlorovinyl trifluoromethyl
ketone and studied its reactions with N,N- and N,S-
nucleophiles.
2,2-Dichlorovinyl trifluoromethyl ketone (I) was
synthesized by the known procedure which is used for
preparation of 2,2-dichlorovinyl ketones: by reaction
of trifluoroacetyl chloride with 1,1-dichloroethene in
the presence of AlCl3 [2, 3]. The reaction was per-
formed with equimolar amounts of the reactants and
the catalyst at 50 to 60 C. It should be noted that
the process was not accompanied by formation of
a saturated product, trichloroethyl trifluoromethyl
ketone, though alkanoyl and benzoyl chlorides are
known to react with 1,1-dichloroethene, yielding the
corresponding 2,2,2-trichloroethyl ketones which are
converted into 2,2-dichlorovinyl ketones by ther-
molysis, treatment with bases, or steam distillation
[3]. Presumably, intermediate carbocation formed in
the reaction of 1,1,-dichloroethene with trifluoroacetyl
to give the final product, rather than through addition
of chloride ion with formation of 2,2,2-trichloroethyl
trifluoromethyl ketone (Scheme 1).
Ketone I is a slightly colored volatile liquid with
a strong specific odor. Unlike alkyl dichlorovinyl
ketones, 2,2-dichlorovinyl trifluoromethyl ketone is
stable to storage and is incapable of undergoing
crotonization to form pyranones [2, 3]. The structure
of ketone I and other compounds derived therefrom
was proved by spectral data and elemental analyses
(Tables 1, 2). The IR spectrum of I contains a number
of absorption bands typical of the C O group and
C C, C H, and CF2 F bonds [4] (Table 1). In
1
the H NMR spectrum of ketone I, as well as in the
1H NMR spectra of alkyl and aryl 2,2-dichlorovinyl
ketones (the spectra of these compounds were not
reported previously), we observed only one olefinic
proton signal (Table 2). As a rule, the olefinic proton
signal in the spectra of alkyl (or aryl) 2,2-dichloro-
vinyl ketones shifts downfield as the electron-acceptor
power of the substituent at the carbonyl group rises.
The olefinic proton signal of ketone I is located in
a weaker field than those of alkyl 2,2-dichlorovinyl
ketones and chloromethyl 2,2-dichlorovinyl ketone
but in a stronger field than the corresponding signal
of dichloromethyl, trichloromethyl, and aryl 2,2-di-
chlorovinyl ketones.
Scheme 1.
By reaction of ketone I with 2,4-dinitrophenyl-
hydrazine we obtained the corresponding hydrazone
II which underwent intramolecular cyclization to
to 5-chloro-1-(2,4-dinitrophenyl)-3-trifluoromethyl-
1070-4280/01/3705-0644$25.00 2001 MAIK Nauka/Interperiodica

SYNTHESIS AND PROPERTIES OF 2,2-DICHLOROVINYL TRIFLUOROMETHYL KETONE
645
Scheme 2.
pyrazole (III) on heating above the melting point or
on treatment with triethylamine (Scheme 2). The
cyclization was accompanied by liberation of HCl.
An analogous transformation was reported for 2,2-di-
chlorovinyl phenyl ketone dinitrophenylhydrazone [7].
As is known [7], alkyl 2,2-dichlorovinyl ketone 2,4-di-
nitrophenylhydrazones do not undergo cyclization to
pyrazoles on treatment with bases or on heating.
The reaction of ketone I with methylhydrazine in
the presence of triethylamine (equimolar amounts
of the reactants) resulted in formation of only cyclic
product, 5-chloro-1-methyl-3-trifluoromethylpyrazole
(IV) (Scheme 2). Pyrazole IV was also formed from
equimolar amounts of ketone I and methylhydrazine
in the absence of dehydrochlorinating agent, but in
this case the conversion of I was not complete and
the yield of the product was lower. We succeeded in
increasing the yield of IV by reacting ketone I with
2 equiv of methylhydrazine. Compounds II and III
are strongly colored crystalline substances. Pyrazole
IV is a liquid with a pungent odor.
2,2-Dichlorovinyl ketones are known to react with
thiourea and N-acetylthiourea to afford, respectively,
2-amino- and 2-acetylamino-1,3-thiazine-6-thiones
[10]. We performed analogous reactions of triluoro-
methyl ketone I with thiourea and thioacetamide in
alcohol. These reactions involved replacement of both
chlorine atoms with simultaneous heterocyclization to
give 2-amino-4-trifluoromethyl-1,3-thiazine-6-thione
(V) and 2-methyl-4-trifluoromethyl-1,3-thiazine-6-
thione (VI), respectively (Scheme 3).
Scheme 3.
The presence of a halogen atom in 3-trifluoro-
methylpyrazoles III and IV provides the possibility
for synthesizing promising biologically active sub-
stances, herbicides, dyes, and fluorescent compounds
[1, 8, 9].
Compounds V and VI are colored solids with
a specific odor. The IR spectra of V and VI contained
absorption bands typical of C C, C N, and C S
bonds, which were located at shorter frequencies than
the corresponding bands of known 4-alkyl(aryl)-2-
amino-1,3-thiazine-6-thiones [10]. In the 1H NMR
spectra of compounds V and VI we observed only
signals from the olefinic proton (Table 2) and methyl
group for thiazine VI. The 5-H signal of VI appears in
a weaker field ( 7.23 ppm) than those of compound
V and 4-alkyl(aryl)-2-amino-1,3-thiazine-6-thiones
[10] (Table 1). This fact may be explained by increase
of electron density in the thiazine ring of 2-amino-
thiazinethiones due to effect of lone electron pair on
The IR spectrum of 2,4-dinitrophenylhydrazone II
contains an absorption band of the NH group, which
is absent in the spectrum of cyclization product III.
Instead, a band from the C H bond appears at
1
at 3110 cm . A similar band is present in the IR
spectrum of pyrazole IV. Its frequency is higher than
the C H vibration frequency in the spectrum of initial
hydrazone II (Table 1). Pyrazoles III and IV also
showed in the IR spectra absorption bands belonging
1
to the C C and C N bonds. In the H NMR spec-
trum of IV we observed signals from the CH and
NCH3 protons.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 5 2001

646
LEVKOVSKAYA et al.
Scheme 4.
the amino nitrogen atom, which is transmitted through
the conjugated bond system.
and hydrazines both chlorine atoms and the carbonyl
oxygen atom are replaced simultaneously, leading to
formation of 1,3-thiazine and pyrazole derivatives,
respectively; the reaction with o-phenylenediamine
involves only the halogen atoms and yields 2-(tri-
fluoroacetonyl)benzimidazole.
2-(3,3,3-Trifluoroacetonyl)benzimidazole was pre-
viously synthesized [11, 12] by reaction of 2,2-di-
ethoxyvinyl trifluromethyl ketone or ethyl trifluoro-
acetoacetate with o-phenylenediamine (yield 70 and
15%, respectively). We have found that the reaction
of ketone I with o-phenylenediamine also leads to
formation of 2-(3,3,3-trifluoroacetonyl)benzimidazole
(VII) in 70% yield (Scheme 4, Table 1).
EXPERIMENTAL
1
The H and 19F NMR spectra were obtained on
Bruker DPX-400 (400 and 376.3 MHz, respectively)
and Jeol FX-90Q spectrometers (90 and 84 MHz,
respectively). Hexamethyldisiloxane was used as
According to the IR and NMR spectra, trifluoro-
acetonylbenzimidazole VII exists in different tauto-
meric forms. The ketone tautomer predominates in
the crystalline state. The IR spectrum of benzimid-
azole VII in KBr contains absorption bands of the
C O, N H, C C, and C H (alkyl and aryl) bonds.
It should be noted that the carbonyl vibration fre-
quency of trifluoroacetonylbenzimidazole VII is
appreciably lower than the carbonyl frequency of
initial trifluoromethyl ketone I.
internal reference (for 1H). The IR spectra were
recorded on a Specord IR75 instrument from samples
prepared as KBr pellets or thin films.
2,2-Dichlorovinyl trifluoromethyl ketone (I).
Trifluoroacetyl chloride, 48 g (0.36 mol), was added
through a gas-inlet tube into a suspension of 48 g
(0.36 mol) of AlCl3 in 50 ml of anhydrous chloroform
or methylene chloride, stirred at 50 to 60 C.
1,1-Dichloroethene, 35 g (0.36 mol), was then added
dropwise, and the mixture was stirred for 2 h,
gradually raising the temperature to ambient. The
mixture was treated with ice, the organic layer
was separated, the aqueous layer was extracted with
chloroform, and the combined organic layers were
dried over CaCl2 and evaporated. The residue was
distilled, a fraction with bp 103 110 C being col-
lected. Repeated distillation gave 40.6 g of pure
1
Compound VII showed in the H NMR spectrum
signals from four aromatic proton, a one-proton signal
at
5.41 (DMSO-d6) or 5.5 ppm (CD3OD), and
a broadened downfield signal from the NH proton
at 12 13 ppm. Likewise, in the H NMR spectrum
1
of VII, recorded in CDCl3, only one olefinic proton
signal was observed at 6.1 ppm [11]. According to
[11], the NH proton signal is overlapped by signals
from the imidazole ring protons, and the broadened
downfield signal at 9.1 ppm was assigned to the OH
group. We observed no hydroxy proton signal in the
1H NMR spectra of benzimidazole VII in DMSO-d6
and CD3OD. This fact may be explained by H D
exchange with the solvent, as well as by formation of
intramolecular hydrogen bond C O H N .
Obviously, the formation of intramolecular hydro-
gen bond C O H N like that proposed in [13] for
2-phenacylbenzimidazole is also typical of the ketone
tautomer of compound VII in the crystalline state.
As a result, the carbonyl absorption frequency in the
IR spectrum of VII is anomalously low.
Thus, the chemical properties of 2,2-dichlorovinyl
trifluoromethyl ketone are determined by the presence
of two labile chlorine atoms and highly electrophilic
carbonyl group. In reactions with S,N-dinucleophiles
product I, bp 108 110 C, n2D0 1.4210; d420 1.6523.
Found, %: C 25.15; H 0.52. C4HCl2F3O. Calculated,
%: C 24.87; H 0.52.
2,2-Dichlorovinyl trifluoromethyl ketone 2,4-di-
nitrophenylhydrazone (II). 2,2-Dichlorovinyl tri-
fluoromethyl ketone (I), 1.93 g (0.01 mol), was added
with stirring to a solution of 1.76 g (0.01 mol) of
2,4-dinitrophenylhydrazine in 15 ml of anhydrous
methanol containing 0.5 ml of concentrated sulfuric
acid. When the exothermic reaction was complete, the
mixture was stirred for 15 min at 60 C. The precip-
itate was filtered off and dried in a vacuum desiccator.
Yield 2.30 g. Found, %: C 31.89; H 1.31; Cl 19.31;
N 15.05. C10H5Cl2F3N4O4. Calculated, % C 32.19;
H 1.35; Cl 19.00; N 15.02.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 5 2001

SYNTHESIS AND PROPERTIES OF 2,2-DICHLOROVINYL TRIFLUOROMETHYL KETONE
647
Table 1. Yields, melting points, and IR and NMR spectral parameters of compounds I VII
Comp. Yield,
1H and 19F NMR spectra,
or F, ppm
1
mp,
C
IR spectrum (KBr), , cm
no.
%
I
58
108 110a 1050 1330 (CF3) [4], 1575 (C C), 1720 (C O), CDCl3: 7.00 ( CH); 80.30 (CF3)c
3070 ( C H)b
II
62
182 183 1310, 1350, 1510, 1545 (NO2); 1610, 1620 (C N), DMSO-d6: 6.39 s ( CH), 9.46
3100 ( C H); 3265, 3300 (NH)
(NH), 7.52 d, 8.34 d, 9.34 d (J =
10 Hz) (C6H3)
III
IV
V
68
56
50
50
70
84 86
1330, 1350, 1510, 1550 (NO2); 1600, 1625 (C N,
C C); 3110 ( C H)
140 141a 790 (C Cl), 1280 (CF2 F) [4], 1480 (C C), 2960 CD3Cl: 3.88 s (NCH3), 6.47 s
(CH3), 3150 ( C H)b ( CH); 63.40 s (CF3)c
177 178 1300 (C S); 1500, 1570 (C C); 1635 (C N); CD3OD: 6.85 s ( CH), 70.15 s
3100 ( C H); 3295 (NH2)
(CF3)c
1300 (C S); 1510, 1590 (C C, C N); 2930, 2970 CD3OD: 7.23 s ( CH), 2.61 s
(CH3); 3045 ( C H)
(CH3); 69.93 s (CF3)c
289 291 1483 (C C); 1603 (C N); 1632 (C O); 2653 DMSO-d6: 7.49 m, 7.21 m (C7H5),
VI
VII
53 55
2923 (N H , C H); 3040, 3080 ( C H);
5.414 s ( CH), 13 12 (NH)
3250 (N H)
a
b
c
Boiling point.
The IR spectrum was recorded from thin film.
Relative to CCl3F.
5-Chloro-1-(2,4-dinitrophenyl)-3-trifluoro-
reaction was complete, the mixture was stirred for
1 2 h. The precipitate was filtered off, and the filtrate
was evaporated to isolate 5.45 g (56%) of product IV.
When the reaction of 2,2-dichlorovinyl trifluoro-
methyl ketone with methylhydrazine was performed
at a reactant ratio of 1:2 in ether, hexane, benzene,
and lower alcohols (methanol, ethanol, or 2-propanol),
other conditions being equal, pyrazole IV was ob-
tained in 50 60% yield.
methylpyrazole (III). 2,2-Dichlorovinyl trifluoro-
methyl ketone 2,4-dinitrophenylhydrazone (II), 1.58 g
(0.005 mol), was heated at 185 C. Evolution of HCl
was observed over a period of 5 min. The product was
recrystallized from alcohol. Yield 1.08 g (68%).
Found, %: C 35.18; H 1.24; Cl 10.38; N 16.09.
C10H4ClF3N4O4. Calculated, % C 35.68; H 1.20;
Cl 10.00; N 16.64.
5-Chloro-1-methyl-3-trifluoromethylpyrazole
(IV). a. Methylhydrazine sulfate, 1.46 g (0.01 mol),
was mixed with 15 ml of anhydrous ethanol, and
a solution of 1.45 g (0.0075 mol) of ketone I in 5 ml
of anhydrous ethanol was added dropwise with stir-
ring. Triethylamine, 1.95 g (0.03 mol), was then
added, and the mixture was stirred for 2 h. The precip-
itate of triethylamine sulfate and hydrochloride was
filtered off, and the filtrate was evaporated to isolate
5.46 g of pyrazole IV. Found, %: C 35.18; H 1.24;
Cl 10.38; N 16.09. C10H4ClF3N4O4. Calculated, %:
C 35.68; H 1.20; Cl 10.00; N 16.64.
b. Ketone I, 10.97 g (0.0619 mol), was slowly
added (dropwise) to a solution of 0.1238 mol of
methylhydrazine in 40 50 ml of anhydrous aceto-
nitrile. The mixture warmed up, and methylhydrazine
hydrochloride precipitated. When the exothermic
2-Amino-4-trifluoromethyl-6H-1,3-thiazine-6-
thione (V). 2,2-Dichlorovinyl trifluoromethyl ketone
(I), 3.06 g (0.016 mol), was added dropwise with
stirring to a solution of 2.44 g (0.032 mol) of thiourea
in 50 ml of ethanol. When the exothermic reaction
was complete, the mixture was stirred for 4 h at 40 C
and poured into cold water. The yellow flaky precip-
itate was filtered off and dried in a vacuum desiccator.
Yield 1.7 g. Found, %: C 27.79; H 1.72; N 13.25;
S 29.60. C5H3F3N2S2. Calculated, %: C 28.29;
H 1.41; N 13.20; S 30.17.
2-Methyl-4-trifluoromethyl-6H-1,3-thiazine-6-
thione (VI). 2,2-Dichlorovinyl trifluoromethyl ketone
(I), 1.93 g (0.01 mol), was added dropwise with
stirring to a solution of 1.5 g (0.02 mol) of thioacet-
amide in 32 ml of methanol. When the exothermic
reaction was complete, the mixture was stirred for
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 5 2001

648
LEVKOVSKAYA et al.
1
Table 2. Chemical shifts of the dichlorovinyl group proton in the H NMR spectra of 2,2-dichlorovinyl trifluoromethyl
a
ketone (I) and ketones RCOCH CCl2 (Ia In) in dilute solutions in CCl4 and CDCl3
Comp.
no.
p
*
R
, ppm
[5], ( *) [6]
[5], ( ) [6]
[5]
[5]
[6]
C
I
I
Ia
Ib
Ic
Id
Ie
Ib
CH3
C2H5
C3H7
iso-C3H7
CH2Cl
CF3
6.45
6.54
6.53
6.59
6.95
7.00
7.09
7.20
7.08
7.12
7.17
7.11
7.12
7.20
7.24
0.00 (0.0)
0.10 ( 0.10)
0.15 ( 0.115)
0.19
0.05 ( 0.08)
0.05 ( 0.09)
0.129
0.117
0.15
0.14
0.07 ( 0.11)
0.17 (0.14)
0.42
0.098
0.532
0.15
0.03
1.05 ( 1.09)
If
CHCl2
CCl3
(1.94)
Ig
Ih
Ii
Ij
Ik
Il
2.65 [6]
0.32
0.52
4-CH3OC6H4
4-CH3C6H4
C6H5
4-BrC6H4
4-ClC6H4
4-NO2C6H4
3-NO2C6H4
0.26 (0.29)
0.05 ( 0.08)
0.0
0.45 (0.44)
0.47 (0.47)
0.63 (0.60)
0.63 (0.60)
0.268
0.17
0.0
0.232
0.227
0.778
0.710
0.111
0.129
0.0
0.265
0.238
0.778
0.710
0.17 ( 0.12 [5])
0.0
0.22
0.24
0.15
0.08
Im
In
a
p
*
is the Hammett constant,
the conjugation constant.
In CDCl3.
is the Taft constant,
is the inductive constant,
is the substituent constant [5], and
is
C
I
b
3 h at 50 C and poured into water. The precipitate
was filtered off and dried in a vacuum desiccator.
Yield 1.05 g. Found, %: C 34.24; H 1.82; N 5.80;
S 29.50. C6H4F3NS2. Calculated, %: C 34.12; H 1.91;
N 6.63; S 30.36.
4. Berney, C.V. and Cormier, A.D., Spectrochim. Acta,
Part A, 1977, vol. 33, pp. 929 935.
5. Gordon, A.J. and Ford, R.A., The Chemist’s Compa-
nion, New York: Wiley, 1972. Translated under the
title Sputnik khimika, Moscow: Mir, 1976, p. 172.
6. Zhdanov, Yu.A. and Minkin, V.I., Korrelyatsionnyi
analiz v organicheskoi khimii (Correlation Analysis
in Organic Chemistry), Rostov-on-Don: Rostov. Gos.
Univ., 1966.
7. Kalikhman, I.D., Levkovskaya, G.G., Lavlin-
skaya, L.I., Mirskova, A.N., and Atavin, A.S., Izv.
Akad. Nauk SSSR, Ser. Khim., 1973, no. 10,
pp. 2235 2240.
2-(Trifluoroacetonyl)benzimidazole (VII). 2,2-Di-
chlorovinyl trifluoromethyl ketone, 2 g (0.01034 mol),
was added dropwise with stirring to a solution of
1.12 g (0.01034 mol) of o-phenylenediamine in 60 ml
of dry diethyl ether. When the exothermic reaction
was complete, the mixture was stirred for 3 h. The
precipitate of 2-(trifluoroacetonyl)benzimidazole
hydrochloride, mp 166 169 C, was filtered off, dried
in a vacuum desiccator, and treated with a solution of
sodium carbonate. The precipitate of VII was filtered
off and dried. Yield 1.65 g, mp 289 291 C. Found,
%: C 52.37; H 3.42; N 12.14. C10H7F3N2O. Calcu-
lated, %: C 52.46; H 3.09; N 12.28.
8. JPN Patent no. 06-56792, 1993; Chem. Abstr., 1995,
vol. 122, no. 31573f.
9. Nazarinia, M., Sharifian, A., and Shafiee, A.,
J. Heterocycl. Chem., 1995, vol. 32, pp. 223 225.
10. Mirskova, A.N., Levkovskaya, G.G., and Ata-
vin, A.S., Zh. Org. Khim., 1976, vol. 12, no. 4,
pp. 904 905.
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