Reactions of 1,2,4-trichlorotrifluorobenzene with nucleophiles

Article abstract of DOI:10.1134/S107042801601005X

1,2,4-Trichlorotrifluorobenzene reacted with potassium hydrogen sulfide, potassium hydroxide, sodium isopropoxide, liquid ammonia, and ethyl cyanoacetate via nucleophilic substitution of one fluorine atom with predominant formation of the isomer in which

Full text of DOI:10.1134/S107042801601005X

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2016, Vol. 52, No. 1, pp. 25–31. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © P.V. Nikul’shin, A.M. Maksimov, V.E. Platonov, 2016, published in Zhurnal Organicheskoi Khimii, 2016, Vol. 52, No. 1, pp. 33–39.
Reactions of 1,2,4-Trichlorotrifluorobenzene with Nucleophiles
P. V. Nikul’shin, A. M. Maksimov, and V. E. Platonov
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: platonov@nioch.nsc.ru
Received July 15, 2015
Abstract—1,2,4-Trichlorotrifluorobenzene reacted with potassium hydrogen sulfide, potassium hydroxide,
sodium isopropoxide, liquid ammonia, and ethyl cyanoacetate via nucleophilic substitution of one fluorine
atom with predominant formation of the isomer in which the new substituent replaced fluorine atom in the
5-position.
DOI: 10.1134/S107042801601005X
Polyfluorochlorobenzenes are important interme-
diate products in the synthesis of a wide range of
polyfluoroaromatic compounds containing various
functional groups [1]. Among polyfluorochloroben-
zenes, trichlorotrifluoro derivatives remain poorly
studied. The reaction of hexachlorobenzene with
potassium fluoride was reported [2, 3] to give ~12%
of a mixture of isomeric trichlorotrifluorobenzenes,
where the major component was 1,3,5-trichlorotri-
fluorobenzene (~69%), and the fractions of the 1,2,3-
and 1,2,4-trichloro isomers were ~18 and 13%, respec-
tively. 1,3,5-Trichlorotrifluorobenzene was the only
product isolated in the pure state [3]. 1,2,4-Trichloro-
trifluorobenzene (1) was synthesized in 11% yield by
reaction of 1,2,4,5-tetrachloro-3,3,6,6-tetrafluorocyclo-
hexa-1,4-diene with potassium fluoride at 525°C [4].
Compound 1 was also obtained by bromination of
1,2,4-trifluorobenzene to 1,2,4-tribromotrifluoroben-
zene, followed by replacement of the bromine atoms
by chlorine (overall yield 53%) [3].
presence or in the absence of water [7]. Fluorine atoms
therein were replaced by the action of such nucleo-
philes as hydrazine in alcohol [8], sodium azide in
DMSO [9], and potassium hydroxide in tert-butyl
alcohol [10]. 1,3,5-Trichlorotrifluorobenzene was con-
verted into organolithium [11], organomagnesium [12],
and organozinc compounds [7]. 3,5-Dichloro-2,4,6-tri-
fluorophenyllithium was used to introduce 3,5-di-
chloro-2,4,6-trifluorophenyl ligands into platinum and
palladium complexes [13], and its reactions with nickel
compounds were also reported [11].
Only a few data are available on the chemical trans-
formations of 1,2,4-trichlorotrifluorobenzene (1). The
substitution of chlorine by fluorine in isomeric tri-
chlorotrifluorobenzenes, including compound 1, by the
action of potassium fluoride was described in [14], and
chlorine atoms were replaced by hydrogen via reduc-
tion with zinc in DMF in the presence of water [7].
The synthesis of 1 from dichlorotetrafluoroben-
zenes made it possible to examine its reactions with
some nucleophiles, which may be interesting from
the viewpoint of synthesis of physiologically active
compounds, by analogy with 1,2,4-trichlorobenzene
derivatives [15, 16].
We have recently developed a procedure for the
preparation of polyhalobenzene 1 from a crude mixture
of isomeric dichlorotetrafluorobenzenes formed in the
reaction of hexachlorobenzene with KF [2, 3]. The
procedure is based on the transformation of that mix-
ture into isomeric dichlorotrifluorobenzenethiols by
treatment with potassium hydrogen sulfide and subse-
quent chlorination. As a result, arene 1 was isolated in
a good yield [5].
The reaction of 1 with potassium hydrogen sulfide
in DMF afforded 91% of 2,4,5-trichloro-3,6-difluoro-
benzenethiol (2), while only small amounts of isomers
3 and 4 were formed (according to the 19F NMR data;
Scheme 1). However, our attempt to introduce a hy-
droxy group into molecule 1 to obtain 2,4,5-trichloro-
3,6-difluorophenol (5) by heating with aqueous potas-
sium hydroxide for 5 days at ~220°C resulted in a low
conversion (~25%), and the reaction was accompanied
1,3,5-Trichlorotrifluorobenzene has been studied
most thoroughly. In particular, the chlorine atoms in its
molecule were replaced by hydrogens via reactions
with copper and water [6] and with zinc in DMF in the
25

NIKUL’SHIN et al.
26
Scheme 1.
Cl
F
Cl
Cl
Cl
Cl
Cl
(1) KSH, DMF, 31–36°C
(2) HCl
F
SH
F
F
F
HS
Cl
F
F
+
+
Cl
Cl
Cl
SH
Cl
Cl
1
2
3
4
~99
<0.5
<0.5
Scheme 2.
Cl
Cl
Cl
Cl
(1) KOH, H2O, 220°C
(2) HCl
F
OH
F
F
HO
F
F
+
+
F
Cl
Cl
F
Cl
OH
Cl
Cl
Cl
Cl
Cl
1
5
6
7
~81
6
13
by formation of isomeric phenols 6 and 7. The overall
yield of polyfluorochlorophenols 5–7 was ~13%
(Scheme 2).
The reaction of 1 with liquid ammonia according to
the procedure described in [17] afforded 2,4,5-tri-
chloro-3,6-difluoroaniline (11) as the major product
together with minor isomeric trichlorodifluoroanilines
12 and 13 (Scheme 4), the overall yield of 11–13 being
91%. By acylation of mixture 11/12/13 with acetic acid
in the presence of phosphorus(III) chloride we
obtained a mixture of acetyl derivatives 14–16 (91%;
Scheme 5), and recrystallization of the product mixture
gave acetanilide 14. By alkaline hydrolysis of the latter
with aqueous sodium hydroxide we isolated 90% of
pure aniline 11. Arene 1 reacted with ethyl cyano-
acetate in dimethylformamide in the presence of
potassium carbonate to give mainly ester 17 and
By contrast, compound 1 reacted with sodium iso-
propoxide in isopropyl alcohol under mild conditions,
and the major product was 1,2,4-trichloro-3,6-difluoro-
5-isopropoxybenzene (8). In addition, small amounts
of 1,2,4-trichloro-3,5-difluoro-6-isopropoxybenzene
(9) and 1,2,4-trichloro-5,6-difluoro-3-isopropoxyben-
zene (10) were obtained (Scheme 3). The overall yield
of isopropoxy derivatives 8–10 was 91%. Treatment of
mixture 8/9/10 (89 : 4 : 7) with sulfuric acid gave
a mixture of polychlorofluorophenols 5, 6, and 7
(91:4:5) with an overall yield of 84%.
Scheme 3.
Cl
F
Cl
Cl
Cl
F
OPr-i
F
F
i-PrO
F
F
i-PrONa, i-PrOH, ~68°C
+
+
Cl
Cl
F
Cl
OPr-i
Cl
Cl
Cl
Cl
Cl
1
8
9
10
~89
4
7
Scheme 4.
Cl
F
Cl
Cl
Cl
Cl
F
NH2
F
F
H2N
F
F
NH3 (liquid), ~50°C
+
+
Cl
Cl
F
Cl
NH2
Cl
Cl
Cl
Cl
13
1
11
12
~92
1
7
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 1 2016

REACTIONS OF 1,2,4-TRICHLOROTRIFLUOROBENZENE WITH NUCLEOPHILES
27
Scheme 5.
Cl
Cl
Cl
F
NHAc
F
F
F
AcNH
Cl
F
F
PCl3, AcOH, 50°C
11 + 12 + 13
+
+
Cl
Cl
NHAc
Cl
Cl
Cl
14
~92
15
1.5
16
6.5
Scheme 6.
Cl
F
Cl
CN
Cl
CN
Cl
Cl
NCCH2C(O)OEt
K2CO3, DMF, 95–100°C
F
OEt
F
F
EtO
F
F
O
+
+
O
F
O
Cl
Cl
Cl
OEt
Cl
Cl
Cl
Cl
CN
1
17
~97.5
18
1
19
1.5
EXPERIMENTAL
insignificant amounts of isomers 18 and 19 with
an overall yield of 89% (Scheme 6).
The analytical and spectral studies were performed
at the Joint Chemical Service Center, Siberian Branch,
The regioselectivity observed in the reactions of 1
with nucleophiles may be rationalized by comparing
the stabilities of possible intermediate σ-complexes
A–C (Scheme 7). The activating effect of chlorine
atoms in different positions of benzene ring toward
fluorine atoms in polyfluorochlorobenzenes (C6F5Cl,
C6F4Cl2) weakly depends on the nucleophile or solvent
nature and can be expressed by the following relations:
ortho–meta–para 3.2:0.69:35 (in the reactions with
sodium methoxide in methanol) and 3:1:27 (in the
reactions with ammonia in aqueous dioxane) [18].
Presumably, the orienting effect of chlorine atoms in
molecule 1 in nucleophilic substitution reactions is
also determined by their position with respect to the
reaction center. Then, the stability of intermediate σ-
complexes should decrease in the series A > C > B.
The experimental isomer ratios are consistent with the
above stability series of σ-complexes which are likely
to represent the structures of transition states in the
two-step substitution process where nucleophile ad-
dition is the rate-determining step.
1
Russian Academy of Sciences. The H and 19F NMR
spectra were recorded on a Bruker AV-300 instrument
at 300 and 282.4 MHz, respectively, using carbon
tetrachloride with addition of CDCl3 as solvent. The
19F chemical shifts were measured relative to hexa-
fluorobenzene as internal standard. Signals in the
19F NMR spectra were assigned with account taken of
chemical shifts calculated by the additivity scheme
[19]. The IR spectra were recorded on a Bruker Vector
22 IR spectrometer. The UV spectra were registered
with a Hewlett Packard 8453 spectrophotometer. The
molecular weights and elemental compositions were
determined from the high-resolution mass spectra
which were obtained using a DFS instrument (electron
impact, 70 eV). Gas chromatographic–mass spectro-
metric analysis was performed on HP 5890/5971 and
Agilent 6890N/5973N GC/MSD systems (electron
impact, 70 eV; ion source temperature 173°C; HP-5
column, 30 m×0.25 mm×0.25 μm; carrier gas helium,
flow rate 1 mL/min; oven temperature programming
Scheme 7.
Cl
F
Cl
Cl
Cl
F
Nu
F
F
F
F
F
Nu–
Nu
+
F
+
Nu
Cl
Cl
F
Cl
Cl
F
Cl
Cl
Cl
Cl
1
A
B
C
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 1 2016

NIKUL’SHIN et al.
28
from 50 to 280°C). GLC analyses were obtained on
an HP 5890 gas chromatograph equipped with a ther-
mal conductivity detector (HP-5 column, 30 m×
0.52 mm×2.6 μm).
with 1.11 g (4.72 mmol) of compound 1, 0.63 g
(11.63 mmol) of potassium hydroxide, and 3.16 g of
water. The ampule was sealed and heated for 5 days at
219–221°C. After cooling, the mixture was treated
with 2 mL of concentrated aqueous HCl and 2 mL of
water and extracted with methylene chloride (3×
3 mL). The extract was dried over CaCl2, and the sol-
vent was removed on a rotary evaporator. The residue
was 0.97 g of a mixture of unreacted compound 1 and
isomers 5–7 at a ratio of ~87:13 (19F NMR; 85.4:14.6,
GLC; ratio 5:6:7 ~81:6:13, 19F NMR).
1,2,4-Trichlorotrifluorobenzene (1) with a purity of
99% (GLC) was synthesized according to [5]. A solu-
tion of potassium hydrogen sulfide in ethylene glycol
(~4.1 M) was prepared by passing gaseous hydrogen
sulfide through a solution of 2 mol of KOH in 330 mL
of ethylene glycol until a gain in weight of 64 g was
attained.
Reaction of 1,2,4-trichlorotrifluorobenzene (1)
with potassium hydrogen sulfide. Compound 1,
76.55 g (0.33 mol), was dissolved in 330 mL of DMF,
and 170 mL of a solution of KSH (prepared as de-
scribed above) was added under stirring over a period
of 0.7 h, maintaining the temperature below 35°C. The
mixture was then stirred for 2.2 h at 32–36°C and
poured into 400 mL of a mixture of concentrated
aqueous HCl and 700 g of ice. The precipitate was
filtered off and dried in a desiccator over CaCl2. The
product, 75.52 g, contained 99.5% (GLC) of a mixture
of thiols 2, 3, and 4 (yield 91%) at a ratio of
~99:<0.5:<0.5 (19F NMR). Found (for mixture 2/3/4),
%: C 28.84; H 0.35; Cl 42.40; F 15.02; S 12.80.
C6HCl3F2S. Calculated, %: C 28.88; H 0.40; Cl 42.63;
F 15.23; S 12.85.
Reaction of 1,2,4-trichlorotrifluorobenzene (1)
with sodium isopropoxide. A solution of sodium iso-
propoxide prepared from 1.24 g (53.93 mmol) of
sodium and 100 mL of isopropyl alcohol was added
under stirring to a solution of 9.81 g (41.67 mmol) of
compound 1 in 30 mL of isopropyl alcohol, main-
taining the temperature below 68°C. The mixture was
stirred for 2 h at 65–68°C, cooled, and poured into
a mixture of 50 mL of concentrated aqueous HCl and
100 mL of water. The organic layer (11.09 g) was
separated and dried over CaCl2. According to the GLC
data, the overall concentration of isomers 8, 9, and 10
in the reaction mixture was 94% (yield 91%); ratio
8 :9 :10 ~90:4 :6 (19F NMR). Vacuum distillation
(~33 mm) of 10.11 g of mixture 8–10 gave 1.64 g of
a fraction boiling below 144°C, which contained 96%
of 8–10 (GLC) at a ratio of ~89:4:7 (19F NMR) and
6.26 g of a fraction with bp 144–145°C which
contained 98.1% of 8–10 (GLC) at the same ratio
(19F NMR). Found (for mixture 8–10), %: C 39.70;
H 2.68; Cl 38.70; F 13.58. m/z 273.9524 [M]+.
C9H7Cl3F2O. Calculated, %: C 39.24; H 2.56;
Cl 38.60; F 13.79. M 273.9525.
2,4,5-Trichloro-3,6-difluorobenzenethiol (2).
mp 97.5–99°C [after sublimation at 140–150°C
(12 mm)]. IR spectrum (KBr), ν, cm–1: 2590, 1747,
1516, 1476, 1435, 1391, 1339, 1292, 1259, 1169,
1099, 1016, 988, 951, 887, 854, 799, 777, 754, 719,
669, 629. UV spectrum (hexane), λmax, nm (logε): 218
1
(4.35), 244 (4.14), 289 (3.34), 297 (3.36). H NMR
spectrum, δ, ppm: 4.08 d.d (SH, JH, 6-F = 2, JH, 3-F
=
=
1 Hz). 19F NMR spectrum, δF, ppm: 49.5 d.d (3-F, JFF
1,2,4-Trichloro-3,6-difluoro-5-isopropoxyben-
1
zene (8). H NMR spectrum (from the spectrum of
12, JFH = 1 Hz), 54.6 d.d (6-F, JFF = 12, JFH = 2 Hz).
Found: m/z 247.8831 [M]+. C6HCl3F2S. Calculated:
M 247.8827.
isomer mixture), δ, ppm: 1.36 d.d (6H, CH3, JHH = 6,
JH,6-F ≈ 1 Hz), 4.52 sept.d (1H, CH, JHH = 6, JH,6-F
≈
1 Hz). 19F NMR spectrum (from the spectrum of
isomer mixture), δF, ppm: 33.5 d.m (6-F, JFF = 9.5 Hz),
48.0 d (3-F, JFF = 9.5 Hz).
2,3,5-Trichloro-4,6-difluorobenzenethiol (3).
19F NMR spectrum (from the spectrum of isomer mix-
ture), δF, ppm: 49.7 d (4-F, JFF = 1.5 Hz), 56.4 m (6-F).
Found: m/z 248 [M]+. Calculated: M 247.88.
1,2,4-Trichloro-3,5-difluoro-6-isopropoxyben-
zene (9). 19F NMR spectrum (from the spectrum of
isomer mixture), δF, ppm: 35.1 s (5-F), 46.8 s (3-F).
2,3,6-Trichloro-4,5-difluorobenzenethiol (4).
19F NMR spectrum (from the spectrum of isomer mix-
ture), δF, ppm: 28.2 d (JFF = 21 Hz), 30.5 d (JFF
=
1,2,4-Trichloro-5,6-difluoro-3-isopropoxyben-
zene (10). 19F NMR spectrum (from the spectrum of
isomer mixture), δF, ppm: 25.8 d (JFF = 22 Hz), 28.2 d
(JFF = 22 Hz).
21 Hz). Found: m/z 248 [M]+. Calculated: M 247.88.
Reaction of 1,2,4-trichlorotrifluorobenzene (1)
with potassium hydroxide. An ampule was charged
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 1 2016

REACTIONS OF 1,2,4-TRICHLOROTRIFLUOROBENZENE WITH NUCLEOPHILES
29
Reaction of isopropoxybenzenes 8–10 with sul-
furic acid. A mixture of 5.09 g (18.48 mmol) of iso-
mer mixture 8–10 (~89:4:7, 19F NMR) and 30 mL of
~83% sulfuric acid was stirred for 13 h at 95–100°C.
The mixture was cooled and extracted with methylene
chloride (4×15 mL), the extract was dried over CaCl2
and evaporated on a rotary evaporator, and the residue,
4.74 g, was subjected to vacuum sublimation at 130–
135°C (~10 mm). The product, 3.62 g, contained
99.5% (GLC) of a mixture of isomers 5, 6, and 7 at
a ratio of ~91 :4:5 (19F NMR). Found (for isomer
mixture 5–7), %: C 30.90; H 0.45; Cl 44.92; F 16.64.
m/z 231.9053 [M]+. C6HCl3F2O. Calculated, %:
C 30.87; H 0.43; Cl 45.56; F 16.28. M 231.9056.
11 :12 :13 ~92 :1:7 (19F NMR). Found (for isomer
mixture 11–13), %: C 30.66; H 0.84; Cl 45.75;
F 16.37; N 5.77. C6H2Cl3F2N. Calculated, %: C 31.00;
H 0.87; Cl 45.76; F 16.35; N 6.03.
2,3,5-Trichloro-4,6-difluoroaniline (12). 19F NMR
spectrum (from the spectrum of isomer mixture), δF,
ppm: 28.1 d (6-F, JFF = 4 Hz), 36.5 d (4-F, JFF = 4 Hz).
Found: m/z 231 [M]+. Calculated: M 230.92.
2,3,6-Trichloro-4,5-difluoroaniline (13). 19F NMR
spectrum (from the spectrum of isomer mixture), δF,
ppm: 15.9 d (4-F, JFF = 22 Hz), 26.8 d (5-F, JFF
=
22 Hz). Found: m/z 231 [M]+. Calculated: M 230.92.
Acetanilides 14–16. Phosphorus(III) chloride,
0.91 g (6.63 mmol), was added to a solution of 4.01 g
(17.25 mmol) of isomer mixture 11–13 (~92:1:7,
19F NMR) in 7.03 g of glacial acetic acid. The mixture
was stirred for 3 h at 50°C, cooled to room tempera-
ture, and poured into 30 mL of water. The precipitate
was filtered off and dried in a desiccator over CaCl2.
The product, 4.30 g, contained 99.9% (GLC, yield
91%) of a mixture of compounds 14, 15, and 16 at
a ratio of ~92:1.5:6.5 (19F NMR). Found (for isomer
mixture 14–16), %: C 34.86; H 1.63; Cl 38.60;
F 14.26; N 4.66. C8H4Cl3F2NO. Calculated, %:
C 35.01; H 1.47; Cl 38.75; F 13.84; N 5.10.
Five recrystallizations of 3.50 g of mixture 5–7
from hexane (~1 mL of the solvent per gram of
substrate) gave 2.01 g of mixture 5–7 at a ratio of
~98:1.5:0.5 (19F NMR).
2,4,5-Trichloro-3,6-difluorophenol (5). mp 61–
63°C (from hexane). IR spectrum (KBr), ν, cm–1: 3410,
1607, 1466, 1454, 1371, 1358, 1341, 1315, 1308,
1246, 1092, 881, 711, 644. UV spectrum (hexane),
λ
max, nm (logε): 223 (4.06), 285 (3.20). 1H NMR spec-
trum: δ 5.46 ppm, br.s (OH). 19F NMR spectrum, δF,
ppm: 25.3 d (6-F, JFF = 9.5 Hz), 46.7 d (3-F, JFF
=
9.5 Hz). Found, %: C 30.98; H 0.75; Cl 45.50; F 16.22.
m/z 231.9053 [M]+. C6HCl3F2O. Calculated, %:
C 30.87; H 0.43; Cl 45.56; F 16.28. M 231.9056.
2,3,5-Trichloro-4,6-difluorophenol (6). 19F NMR
spectrum (from the spectrum of isomer mixture), δF,
ppm: 27.4 d (6-F, JFF = 3 Hz), 41.6 d (4-F, JFF = 3 Hz).
Found: m/z 232 [M]+. Calculated: M 231.91.
Double recrystallization of mixture 14–16, 4.11 g,
from acetonitrile (~10 mL of the solvent per gram of
substrate) gave 2.74 g of isomer 14 containing less
than 0.5% of each of 15 and 16 (19F NMR).
N-(2,4,5-Trichloro-3,6-difluorophenyl)acetamide
(14). mp 190–191.5°C. IR spectrum (KBr), ν, cm–1:
3242, 3196, 3107, 3017, 2932, 2770, 1682, 1593,
1564, 1522, 1458, 1414, 1375, 1271, 1231, 1092,
1040, 1011, 986, 880, 812, 727, 708, 667, 630, 600,
584, 536. UV spectrum (hexane), λmax, nm (logε):
2,3,6-Trichloro-4,5-difluorophenol (7). 19F NMR
spectrum (from the spectrum of isomer mixture), δF,
ppm: 20.6 d (4-F, JFF = 22 Hz), 27.2 d (5-F, JFF
22 Hz). Found: m/z 232 [M]+. Calculated: M 231.91.
=
1
230 sh (3.73), 288 (3.08). H NMR spectrum
(acetone-d6), δ, ppm: 2.17 s (3H, Me), 9.23 s (NH).
Reaction of 1,2,4-trichlorotrifluorobenzene (1)
with liquid ammonia. A mixture of 5.21 g
(22. 13 mmol) of compound 1 and 11. 46 g
(672.91 mmol) of liquid ammonia was heated for
4 days at 45–50°C in a closed metal vessel. After
cooling, unreacted ammonia was removed, the residue
was extracted with methylene chloride (5×10 mL), the
extract was dried, and the solvent was removed on
a rotary evaporator. The residue, 4.81 g, contained
97.6% (GLC) of compounds 11–13 (yield 91%) at
a ratio of ~92:1:7 (19F NMR). Vacuum sublimation of
4.51 g of the product at 160–170°C (~10 mm) gave
4.23 g of isomer mixture 11–13 (99.1%, GLC); ratio
19F NMR spectrum (acetone-d6), δF, ppm: 47.2 d (JFF
=
10 Hz), 48.9 d (JFF = 10 Hz). Found, %: C 34.65;
H 1.59; Cl 38.73; F 13.87; N 4.79. m/z 272.9323 [M]+.
C8H4Cl3F2NO. Calculated, %: C 35.01; H 1.47;
Cl 38.75; F 13.84; N 5.10. M 272.9321.
N-(2,3,5-Trichloro-4,6-difluorophenyl)acetamide
(15). 19F NMR spectrum (acetone–CDCl3) (from the
spectrum of isomer mixture 14–16), δF, ppm: 48.4 s,
52.6 s. Found: m/z 273 [M]+. Calculated: M 272.93.
N-(2,3,6-Trichloro-4,5-difluorophenyl)acetamide
(16). 19F NMR spectrum (acetone–CDCl3) (from the
spectrum of isomer mixture 14–16), δF, ppm: 29.0 d
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 52 No. 1 2016

NIKUL’SHIN et al.
30
(JFF = 22 Hz), 31.4 d (JFF = 22 Hz). Found: m/z 273
[M]+. Calculated: M 272.93.
(JFF = 12 Hz). Found: m/z 326. 9431 [M]+.
C11H6Cl3F2NO2. Calculated: M 326.9427.
Hydrolysis of N-(2,4,5-trichloro-3,6-difluoro-
phenyl)acetamide (14). A mixture of 1.01 g
(3.68 mmol) of compound 14 and 0.61 g (15.25 mmol)
of sodium hydroxide in 3 mL of water was stirred for
4 days at 85–90°C. The mixture was cooled to room
temperature, and the precipitate was filtered off and
dried in a desiccator over CaCl2.
Ethyl 2-cyano-2-(2,3,5-trichloro-4,6-difluoro-
phenyl)acetate (18). 19F NMR spectrum (MeCN–
CDCl3) (from the spectrum of mixture 17–19), δF,
ppm: 51.8 d (6-F, JFF = 4 Hz), 57.7 d (4-F, JFF = 4 Hz).
Found: m/z 327 [M]+. Calculated: M 326.94.
Ethyl 2-cyano-2-(2,3,6-trichloro-4,5-difluoro-
phenyl)acetate (19). 19F NMR spectrum (MeCN–
CDCl3) (from the spectrum of mixture 17–19), δF,
2,4,5-Trichloro-3,6-difluoroaniline (11). Yield
0.78 g (90%), purity 98.9% (GLC); mp 105–107°C.
IR spectrum (KBr), ν, cm–1: 3499, 3400, 1620, 1589,
1474, 1447, 1364, 1350, 1288, 1232, 1113, 870, 770,
716, 637, 592, 532. UV spectrum (hexane), λmax, nm
ppm: 31.3 d (5-F, JFF = 21 Hz), 38.8 d (4-F, JFF
=
21 Hz). Found: m/z 327 [M]+. Calculated: M 326.94.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 15-03-08869a).
1
(logε), 238 (4.16), 285 (3.45). H NMR spectrum:
δ 4.26 ppm, s (NH2). 19F NMR spectrum, δF, ppm:
26.7 d (6-F, JFF = 10 Hz), 45.9 d (3-F, JFF = 10 Hz).
Found, %: C 30.90; H 1.23; Cl 45.39; F 16.59; N 6.15.
m/z 230.9207 [M]+. C6H2Cl3F2N. Calculated, %:
C 31.00; H 0.87; Cl 45.76; F 16.35; N 6.03.
M 230.9215.
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Reaction of 1,2,4-trichlorotrifluorobenzene (1)
with ethyl cyanoacetate. Compound 1, 5.08 g
(21.58 mmol), was dissolved in 50 mL of DMF, 2.94 g
(25.99 mmol) of ethyl cyanoacetate and 6.04 g
(43.70 mmol) of potassium carbonate were added, and
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~97.5:1:1.5 (19F NMR). Vacuum sublimation at 150°C
(~10 mm) gave white crystals with mp 79–81°C and
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C11H6Cl3F2NO2. Calculated, %: C 40.22; H 1.84;
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1182, 1093, 1070, 1036, 995, 912, 881, 852, 783, 766,
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REACTIONS OF 1,2,4-TRICHLOROTRIFLUOROBENZENE WITH NUCLEOPHILES
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