Two-step regioselective synthesis of 1,2-difluorobenzenes from chlorotrifluoroethylene and buta-l,3-dienes

Article abstract of DOI:10.1007/s11172-020-2724-8

The gas-phase copyrolysis of chlorotrifluoroethylene with buta-1,3-diene, penta-1,3-diene, or isoprene in a flow reactor at 440–480°C gave 4-chloro-4,5,5-trifluorocyclohex-1-enes. The latter treated with aqueous KOH under condition of phase-transfer catalysis were selectively converted into 1,2-difluorobenzene, 2,3-difluorotoluene, or 3,4-difluorotoluene.

Full text of DOI:10.1007/s11172-020-2724-8

Russian Chemical Bulletin, International Edition, Vol. 69, No. 1, pp. 68—75, January, 2020
68
Two-step regioselective synthesis of 1,2-difluorobenzenes
from chlorotrifluoroethylene and buta-1,3-dienes*
N. V. Volchkov, M. B. Lipkind, and O. M. Nefedov
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 6390. E-mail: volchkov@ioc.ac.ru
The gas-phase copyrolysis of chlorotrifluoroethylene with buta-1,3-diene, penta-1,3-diene,
or isoprene in a flow reactor at 440—480 °C gave 4-chloro-4,5,5-trifluorocyclohex-1-enes. The
latter treated with aqueous KOH under condition of phase-transfer catalysis were selectively
converted into 1,2-difluorobenzene, 2,3-difluorotoluene, or 3,4-difluorotoluene.
Key words: chlorotrifluoroethylene, buta-1,3-diene, isoprene, penta-1,3-diene, cycloaddi-
tion, (alkenyl)chlorotrifluorocyclobutanes, chlorotrifluorocyclohexenes, 1,2-difluorobenzene,
3,4-difluorotoluene, 2,3-difluorotoluene.
The unique effect of fluorine atom on the biological
ethylene, and hexafluoropropylene with buta-1,3-dienes
and physicochemical properties of organic compounds
attracts an increased attention to the development of
new syntheses of organofluorine compounds of various
classes.1—7 Of particular interest are fluoroaromatic com-
pounds, which are used in the synthesis of more than
100 modern drugs and agrochemicals and are intensively
explored in the search for new biologically active sub-
stances, components of liquid crystals, and discovery of
new materials.1—7 The conventional approaches to fluor-
ine-containing aromatic compounds implemented in
industry and most of the described new laboratory proce-
dures involve nucleophilic or electrophilic substitution of
hydrogen or appropriate functional groups pre-introduced
into the aromatic ring with fluorine using different fluor-
inating agents.1,2,8—11 An alternative methodology for
production of fluoroarenes is also being developed. It
consists in the synthetic assembly of fluorobenzoid struc-
tures from reactive fluorine-containing synthons (fluori-
nated carbenes, olefins, dienes, and acetylenes), which
can simultaneously act as building blocks and sources of
fluorine bonded to the C atom.12—27 In the present work,
we report on the possibilities of efficient application of this
methodology for the regioselective synthesis of 1,2-diflu-
orobenzenes using thermal cycloaddition of chlorotri-
fluoroethylene to buta-1,3-dienes.
proceed either almost exclusively or predominantly as
[2+2] cycloaddition to form vinylcyclobutanes.28—32
Nevertheless, thermal cycloaddition of polyfluoroolefins
to dienes turned out to be quite applicable for obtaining
cyclohexenes and arenes due to the ability of fluorinated
vinylcyclobutanes to undergo thermal rearrangement with
ring expansion and aromatization.15—20,24—27
Earlier, we16—20 and DuPont researchers25 showed the
fundamental possibility of the synthesis of chlorotrifluoro-
cyclohexenes and difluorobenzenes under conditions of
gas-phase pyrolysis of 2-chloro-1,2,2-trifluoro-3-vinyl-
cyclobutanes obtained by thermal cycloaddition of chloro-
trifluoroethylene (CTFE) to buta-1,3-diene and its de-
rivatives. Herein we described the detailed studies on
optimization of these processes.
The pyrolysis of an equimolar mixture of CTFE and
buta-1,3-diene (1a) in a flow reactor at 410 °C leads to
isomeric 2-chloro-1,2,2-trifluoro-3-vinylcyclobutanes
(2a) ((2S*,3S*)-2a : (2S*,3R*)-2a = 1 : 1)) in 57% yield,
as well as to 4-chloro-4,5,5-trifluorocyclohex-1-ene (3a)
(6% yield) and 1,2-difluorobenzene (4a) (1% yield)
(Scheme 1, Table 1). An increase in the pyrolysis tem-
perature in the range of 410—470 °C is accompanied by
the increase in the fractions of cyclohexene 3a and di-
fluorobenzene 4a with a simultaneous decrease in the
fraction of cyclobutane 2a. Under optimal conditions,
cyclohexene 3a can be obtained in 39% isolated yield.
The data obtained are consistent with the results of
pyrolysis of cyclobutane 2a at the same temperature range
(Table 2) confirming the sequence of the reaction steps of
formation of 2a and its isomerization to cyclohexene 3a
under the reaction conditions. Pyrolysis of cyclobutane
2a at 450—480 °C gives chlorotrifluorocyclohexene 3a as
The most common approach to construct C6 cyclic
carbon skeleton is the Diels—Alder [2+4] cycloaddition
of olefins to 1,3-dienes. However, this reaction is not
typical of fluorinated olefins. The thermal reactions of
tetrafluoroethylene, chlorotrifluoroethylene, trifluoro-
* Dedicated to Academician of the Russian Academy of Sciences
V. V. Lunin on the occasion of his 80th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 0068—0075, January, 2020.
1066-5285/20/6901-0068 © 2020 Springer Science+Business Media, Inc.

1,2-Difluorobenzenes
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 1, January, 2020
69
Scheme 1
1—5: R1 = R2 = R3 = H (a); R1 = R2 = H, R3 = Me (b); R1 = Me, R2 = R3 = H (c); R1 = R3 = H, R2 = Me (d)
the main product, which is likely a result of homolytic
cleavage of the C(2)—C(3) cyclobutane bond and subse-
quent C6 cyclization of the biradical intermediate 5a
stabilized by the allyl fragment (see Scheme 1). The ex-
pected alternative route of the rearrangement of 2a through
the ring opening at the C(3)—C(4) bond and intermediate
6a, which should lead to chlorotrifluorocyclohexene 7a
(Scheme 2), seems to have a small contribution to the
process due to the lower stability of intermediate 6a com-
pared to intermediate 5a additionally stabilized by the
chlorine atom.
It should be noted that similar thermal rearrangements
of 1,1,2,2-tetrafluoro-3-vinylcyclobutane,15—18 in contrast to
rearrangements of compound 2a, proceed mainly via the
ring opening at the C(3)—C(4) bond to give 3,3,4,4-tetra-
fluorocyclohexene (Scheme 2). In this case, the contribution of
an alternative rearrangement pathway (see Scheme 1) lead-
ing to 4,4,5,5-tetrafluorocyclohexene is significantly lower.
Table 1. Composition and yield of copyrolysis products of chlorotrifluoroethylene (CTFE)
and buta-1,3-dienes 1a—c at various temperaturesa
Diene
T/°C
Products (yieldb (%))
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
1c
1c
1c
1c
1c
410
435
450
470
500
580
410
435
450
470
500
400
420
440
460
480
2a (62), (57)c + 3a (9), (6)c + 4a (1)
2a (29) + 3a (37), (31)c + 4a (3)
2a (18) + 3a (45), (39)c + 4a (6)
2a (12) + 3a (41), (32)c + 4a (8)
2a (8) + 3a (31) + 4a (10)
2a (4) + 3a (19) + 4a (18)
2b (57), (52)c + 3b (7) + 4b (1) + 4c (1)
2b (25), (20)c + 3b (32), (27)c + 4b (4) + 4c (2)
2b (18) + 3b (36), (31)c + 4b (7) + 4c (2)
2b (14) + 3b (35) (29)c + 4b (9) + 4c (2)
2b (10) + 3b (30) + 4b (12) + 4c (3)
2с (39), (34)c + 2d (26) (19)c + 3с,d (10), (6)c + 4с (0.5) + 4b (0.3)
2c (22) + 2d (16) + 3с,d (34), (28)c + 4с (2) + 4b (1)
2c (6) + 2d (8) + 3с,d (46), (41)c + 4с (5) + 4b (1)
2c (4) + 2d (6) + 3с,d (42), (35)c + 4с (7) + 4b (3)
2c (3) + 2d (5) + 3с,d (38), (32)c + 4с (9) + 4b (3)
a Conditions: a flow reactor, flow rate of CTFE 0.54 mol h–1, flow rate of 1a—c 0.54 mol h–1
.
b The yield in mixtures was calculated according to the analysis of the pyrolysate by GC and
NMR spectroscopy.
c Isolated yield after distillation of the pyrolysate.

Volchkov et al.
70
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 1, January, 2020
Scheme 2
expected products of their isomerization, methylcyclo-
hexenes 3b (a mixture of two isomers in a ratio of 1.3 : 1,
7% total yield), and small amounts of 2,3-difluorotoluene
(4b) and 3,4-difluorotoluene (4c) (see Table 1). Cyclo-
hexenes 3b become the main products at temperatures of
435—470 °C and can be obtained in 27—31% isolated yields
by fractional distillation of pyrolysates. Copyrolysis of CTFE
and 1b at higher temperatures does not increase the yield
of cyclohexenes 3b due to an increase in the contribution
of the side processes of aromatization and resinification.
Cyclohexenes 3b can also be obtained according to
a two-step scheme involving preliminary synthesis of
cyclobutanes 2b by copyrolysis of CTFE with pentadiene
1b at 410 °C and their subsequent isomerization under
pyrolysis conditions at 450—500 °C (see Table 2). The
highest isolated yield of compound 3b (38%) was achieved
by the pyrolysis of cyclobutane 2b at 480 °C. When tem-
perature is decreased or increased, the yield of cyclo-
hexenes 3b decreases due to lowering of the conversion of
cyclobutanes 2b or an increase in the contribution of
aromatization of cyclohexenes 3b and resinification. It
should be noted that the highest yields of cyclohexenes 3b
are noticeably lower than those observed for similar rear-
rangements of compound 2a, which is probably explained
by the unfavorable steric effect of the methyl group on the
C6 cyclization of intermediate 5b.
2, 6, 7: R1 = R2 = R3 = H (a), R1 = R2 = H, R3 = Me (b),
R1 = Me, R2 = R3 = H (c), R1 = R3 = H, R2 = Me (d)
Similar results were obtained for the thermal reactions
of CTFE with penta-1,3-diene (1b) and isoprene 1c. Thus,
the copyrolysis of CTFE with penta-1,3-diene (1b) (a mix-
ture of E-1b : Z-1b = 1.6 : 1) at 410 °C results in four
expected stereoisomeric 2-chloro-1,1,2-trifluoro-3-(prop-
1-en-1-yl)cyclobutanes (2b) (52% total isolated yield,
ratio of isomers 1.6 : 1.5 : 1 : 1) as the main products, the
It is important to note that the pyrolysis of cyclobutanes
2b gives along with 2,3-difluorotoluene (4b) the expected
Table 2. Composition and yield of pyrolysis products of 3-alkenyl-2-chloro-1,1,2-trifluoro-
cyclobutanes 2a—d at various temperaturesa
Cyclobutane
T/°C
Conversion of 2a—d (%)
Products (yieldb (%))
2a
2a
2a
2a
2b
2b
2b
2b
2b
2c
2с
2c
2с
2d
2d
2d
420
450
480
580
420
450
480
500
580
420
450
470
550
450
475
580
450
470
600
23
78
3a (14) + 4a (1)
3a (48), (42)c + 4a (4)
3a (56), (50)c + 4a (8)
89
96
3a (29)
4a (20) (14)c
22
3b (13) + 4b (1) + 4c (1)
70
3b (39), (32)c + 4b (4) + 4c (1)
3b (44), (38)c + 4b (7) + 4c (2)
3b (40), (34)c + 4b (10) + 4c (2)
3b (26) + 4b (17) + 4c (3)
85
90
95
35
3c (23) + 4c (1) + 4b (1)
82
3с (50), (44)c + 4c (4) + 4b (2)
3c (56), (51)c + 4c (7) + 4b (2)
3с (31) + 4c (15) + 4b (2)
90
98
77
3d (44), (38)c + 4c (5) + 4b (—)
3d (54), (48)c + 4c (9) + 4b (—)
3d (28) + 4c (19) (13)c + 4b (—)
3c,d (47) (41)c + 4c (5)+ 4b (2)
3c,d (55), (50)c + 4c (7) + 4b (3)
3c,d (18) + 4c (17) + 4b (4)
89
98
2c,d
2c,d
2c,d
78—83
88—92
95—98
a Conditions: a flow reactor, flow rate of 2a—d 0.54 mol h–1; flow rate of N2 13.0 L h–1
.
b The yield in mixtures was calculated according to the analysis of the pyrolysate by GC and
NMR spectroscopy.
c Isolated yield after distillation of the pyrolysate.

1,2-Difluorobenzenes
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 1, January, 2020
71
product of dehydrohalogenation of cyclohexenes 3b (see
Scheme 1), and fair amounts of isomeric 3,4-difluoro-
toluene (4c). The formation of product 4c is consistent
with possible competitive isomerization of 2b to cyclohex-
ene 7b and aromatization of the latter (see Scheme 2).
The cycloaddition of CTFE to isoprene 1c under the
copyrolysis conditions at 400 °C proceeds at both multiple
bonds resulting in the corresponding [2+2] cycloadducts
2c and 2d (in a ratio of 1.5 : 1). These compounds can be
separated using a distillation column and obtained in 34
and 19% isolated yields, respectively (see Table 1).
Pyrolysis of cyclobutane 2c at 450—470 °C gives cyclo-
hexene 3c in 50—56% yield (GC data) (44—51% isolated
yield) and difluorotoluenes 4c and 4b (6—9% total yield)
(see Table 2). 3,4-Difluorotoluene (4c) obviously results
from dehydrohalogenation of cyclohexene 3c (see Scheme 1),
while the presence of 2,3-difluorotoluene (4b) in the pyrol-
ysate, as in the case of aromatization of cyclobutane 2b,
can be explained by partial rearrangement of cyclobutane
2c following the competitive Scheme 2.
suggested earlier25,27 turned out to be ineffective. The
transformations 2a → 4a under these conditions provided
22—35% yields, while pyrolysis of compounds 2b and 2c,d
led to inseparable mixtures of 2,3-difluorotoluene (4b)
and 3,4-difluorotoluene (4c) in 12—15% total yield.
Moreover, significant amounts of fluoro- and chlorofluo-
robenzenes were formed in all the cases.
We found a much more efficient procedure for synthe-
sizing difluoroarenes, which consists in the isolation of
chlorotrifluorocyclohexenes 3a—d from the mixtures of
pyrolysis products and their subsequent aromatization by
water-alkaline dehydrohalogenation under phase-transfer
catalysis conditions (Scheme 3). Thus, the reaction of
chlorotrifluorocyclohexene 3a with a 3—4-fold molar
excess of 50% aqueous KOH in the presence of catalytic
amounts of triethylbenzylammonium chloride (TEBAC)
at 85—95 °C gives 1,2-difluorobenzene (4a) in 83% isolated
yield. 2-Chloro-1-fluorobenzene (8a) is formed as a by-
product (7% yield).
Cyclobutane 2d under similar conditions at 450—475 °C
isomerizes to cyclohexene 3d (38—48% isolated yield)
with minor (5—9%) formation of 3,4-difluorotoluene (4c)
(see Table 2). At 580 °C, the yield of arene 4c increases
to 19% with no formation of 2,3-difluorotoluene being
observed, which is consistent with the fact that both com-
petitive routes of isomerization of cyclobutane 2d (see
Schemes 1 and 2) should lead to compound 4c via de-
hydrohalogenation of cyclohexenes 3d or 7d.
Scheme 3
Cyclohexenes 3c and 3d can also be obtained by pyrol-
ysis of a mixture of 2c and 2d at 450—470 °C in 41—50%
total isolated yield or in a single step by copyrolysis of
CTFE and isoprene 1c at 440—460 °C (35—41% total
yield, ratio 3c : 3d = 2.1 : 1) (see Table 1).
3, 4, 8: R1 = R2 = R3 = H (a); R1 = R2 = H, R3 = Me (b);
R1 = Me, R2 = R3 = H (c); R1 = R3 = H, R2 = Me (d)
Reagents and conditions: KOH, H2O, Et3NBnCl, 85—95 °C.
A comparison of the results presented in Tables 1 and
2 allows us to conclude that in terms of the yields of chloro-
trifluorocyclohexenes 3 the one-step version is more
preferable than the alternative two-step procedure. At the
same time, to obtain pure cyclohexenes 3c and 3d, which
have very close boiling points, only a two-step procedure
is suitable via a preliminary synthesis of the mixtures of
2c and 2d from CTFE and isoprene, separation of com-
pounds 2c and 2d, and their subsequent isomerization.
The yields of difluoroarenes 4a—c obtained by pyrol-
ysis of cyclobutanes 2a—d at 420—500 °C do not exceed
5—10% because of the low rate of thermal dehydrohalo-
genation of cyclohexenes 3a—d at this temperature range.
When the temperature of pyrolysis is increased to
550—600 °C, the yield of difluoroarenes increases insig-
nificantly, only up to 15—20%, because of a decrease in
the selectivity of 2 → 3 rearrangements and a sharp increase
in the contribution of resinification.
2,3-Difluorotoluene (4b) and 2-chloro-3-fluorotoluene
(8b) (82% and 6% yield, respectively) were obtained from
cyclohexene 3b under similar conditions. The alkaline
aromatization of cyclohexenes 3c and 3d gave 3,4-difluoro-
toluene (4c) in 82—83% yield with 4-chloro-3-fluoro-
toluene (8c) and 3-chloro-4-fluorotoluene (8d) being
formed as the minor products. A mixture of cyclohexenes
3c and 3d obtained by copyrolysis of CTFE and isoprene
can also be used as a starting material for selective synthe-
sis of 4c in 84% yield. Dehydrohalogenation can be carried
out solvent-free by addition of aqueous alkali to cyclo-
hexenes 3a—d, stirring the reaction mixture at 85—95 °C
for 3—4 h, and subsequent steam distillation to separate
the products.
In conclusion, thermal cycloaddition reactions of
commercially available monomers of chlorotrifluoroeth-
ylene, buta-1,3-diene, penta-1,3-diene, and isoprene were
used to accomplish a simple two- or three-step regioselec-
tive synthesis of 1,2-difluorobenzene, 2,3-difluorotoluene,
or 3,4-difluorotoluene, respectively. We showed the pos-
Aromatization of cyclobutanes 2a—d by gas-phase
heterogeneous pyrolysis in the presence of SiC or metal
oxides (Al2O3, ZnO/Al2O3, V2O5/Al2O3) at 400—500 °C

Volchkov et al.
72
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 1, January, 2020
of this mixture afforded 467.4 g (57%) of 3-chloro-1,1,2-tri-
fluoro-3-vinylcyclobutane 2a ((2S*,3S*)-2a : (2S*,3R*)-2a =
= 1 : 1), b.p. 114—115 °C. Liquified products (140.2 g) col-
lected in the trap cooled with dry ice—ethanol mixture contained
64% of CTFE and 26% of butadiene 1a.
Similar copyrolysis procedure (450 °C) of CTFE and diene
1a at a flow rate of 0.54 mol h–1 of each reactant for 9 h and
subsequent treatment of the crude pyrolysate gave 629.8 g of
a product mixture containing 1.1% of butadiene 1a, 23.5% of
cyclobutanes 2a, 58.7% of cyclohexene 3a, 5.9% of difluorobenz-
ene 4a, and 10.8% (total) of unidentified products. Vacuum dis-
tillation of this mixture using a rectification apparatus afforded
320.6 g (39%) of cyclohexene 3a, b.p. 83—85 °C (130 Torr).
Liquified products (94.4 g) collected in the trap cooled with
dry ice—ethanol mixture contained 63% of CTFE and 22% of
butadiene 1a.
Similar copyrolysis procedure (410 °C) of CTFE and penta-
1,3-diene (1b) (a mixture of E-1b : Z-1b = 1.6 : 1) at a flow rate
of 0.54 mol h–1 of each reactant for 10 h and subsequent treat-
ment of the crude pyrolysate gave 785.2 g of a product mixture
containing 5.8% of pentadiene 1b, 72.7% of cyclobutanes 2b,
9.1% of a mixture of cyclohexenes 3b, 1.9% of a mixture of
difluorotoluenes 4b,c, and 10.5% (total) of unidentified products.
Distillation of this mixture using a rectification apparatus afforded
520.3 g (52%) of cyclobutanes 2b (a mixture of four isomers:
(2S*,3S*)- and (2S*,3R*)-3-chloro-1,1,2-trifluoro-3-(E-prop-
1-en-1-yl)cyclobutanes and (2S*,3S*)- and (2S*,3R*)-3-chloro-
1,1,2-trifluoro-3-(Z-prop-1-en-1-yl)cyclobutanes in the ratio of
1.6 : 1.5 : 1 : 1), b.p. 139—142 °C. Liquified products (120.2 g)
collected in the trap cooled with dry ice—ethanol mixture con-
tained 82% of CTFE and 9% of pentadiene 1b.
Similar copyrolysis procedure (450 °C) of CTFE and penta-
diene 1b at a flow rate of 0.54 mol h–1 of each reactant for 10 h
and subsequent treatment of the crude pyrolysate gave 739.2 g of
a product mixture containing 5.2% of pentadiene 1b, 25.6% of
cyclobutanes 2b, 48.6% of a mixture of cyclohexenes 3b, 8.5%
of a mixture of difluorotoluenes 4b and 4c, and 7.5% (total) of
unidentified products. Vacuum distillation of this mixture using
a rectification apparatus afforded 308.8 g (31%) of cyclohexenes
3b (a mixture of cis-3b and trans-3b, 1 : 1.3), b.p. 68—69 °C
(44 Torr). Liquified products (115.2 g) collected in the trap cooled
with dry ice—ethanol mixture contained 79% of CTFE and 9%
of pentadiene 1b.
sibility to scale-up these procedures by obtaining kilogram
amounts of these products under laboratory conditions,
which were used as the starting compounds for the develop-
ment of new technologies for the synthesis of a series of
fluoroquinolone antibacterial drugs (pefloxacin, cipro-
floxacin, and their analogs).
Experimental
Commercially available chlorotrifluoroethylene (99.5%)
(Poly-Trade, Russia), buta-1,3-diene (99.0%), isoprene (99.0%),
and penta-1,3-diene (98.0%) (Sintez-Kauchuk, Russia) were
used. Isoprene and penta-1,3-diene were additionally distilled
to separate from the polymer products formed during storage.
Commercially available KOH (85%), triethylbenzylammonium
chloride (TEBAC) (99%), 1,2-difluorobenzene, and 3,4-difluoro-
toluene (Sigma-Aldrich) were used as purchased.
GC analysis was performed on Kristal 2000M (Macherey-
Nagel OPTIMA-1 capillary column, 30 m×0.25 mm, carrier gas
helium, flame-ionizing detector) and LHhM-8MD (steel column
3.0 m×0.5 cm, 5% SE-30 on Chromaton N-AW-DMCS, car-
rier gas helium, a katharometer) chromatographs. 1H and
19F NMR spectra were recorded on a Bruker AC-200 spectro-
meter (200.1 (1H) and 188.3 MHz (19F)) in CDCl3 containing
0.05% of Me4Si (an internal standard). 19F NMR chemical shifts
are given relative to CClF3 (an external standard). Mass spectra
were recorded on a Trace GC Ultra instrument equipped with
a Finnigan MAT DSQII mass detector (EI, 70 eV, an ion trap
as an ion source, 200 °C) and a Thermo TR-5ms SQC capillary
chromatographic column (15000×0.25 mm). Fischer HMS-500
and Fischer MMS-255 distillation apparatus were used to sepa-
rate products with close boiling points.
Gas-phase pyrolytic processes (general procedure). A tubular
quartz reactor with an inner diameter of 30 mm and a length of
1000 mm with a coaxially inserted quartz rod 16 mm in diameter
and 1000 mm long was used. The reactor was placed in a tubular
electric heating furnace with a heated zone length of 750 mm.
The length of the measured, conditionally isothermal, heating
zone of the reactor (with a temperature variation of 5 °C from
the set) was 380—390 mm. The reaction temperature was evalu-
ated by the readings of a thermocouple placed in a special quartz
pocket installed in the center of the reaction zone. The reactor
was heated to a pre-set temperature in a stream of nitrogen, then
the starting substrates were fed into the reactor at a constant flow
rate controlled by rheometers (for gases) or a microdosing pump
(for liquids).
Copyrolysis of CTFE and buta-1,3-diene (1a). The gas flows
of CTFE at a constant flow rate of 13.0 L h–1 (0.54 mol h–1) and
buta-1,3-diene (1a) at a constant flow rate of 13.0 L h–1
(0.54 mol h–1) were passed through a tubular reactor heated to
410 °C for 9 h. The pyrolysis products leaving the reactor were
cooled in a water condenser and then collected in two sequen-
tially connected traps cooled with ice—water mixture and dry
ice—ethanol mixture. The resulting crude pyrolysate was steam
distilled to separate resins, gaseous components, and inorganic
products. The obtained distillate was washed with water and dried
with CaCl2 to give 630.8 g of the product mixture containing
(GC and NMR spectroscopy data) 1.1% of butadiene 1a, 80.9%
of cyclobutane 2a, 11.6% of cyclohexene 3a, 1.8% of difluoro-
benzene 4a, and 4.6% (total) of unidentified products. Distillation
Similar copyrolysis procedure (400 °C) of CTFE and isoprene 1c
(flow rate of each reactant 0.54 mol h–1) for 10 h gave 820.21 g
of a product mixture containing 3.9% of isoprene 1c, 47.7% of
cyclobutane 2c, 31.4% of cyclobutane 2d, 11.8% of a mixture of
cyclohexenes 3c,d, 1.1% of difluorotoluenes 4b,c, and 4.1%
(total) of unidentified products. Distillation of this mixture using
a rectification apparatus afforded 340.12 g (34%) of 2-chloro-
1,1,2-trifluoro-3-methyl-3-vinylcyclobutane (2c) ((2S*,3R*)-
2c : (2S*,3S*)-2c = 1 : 1), b.p. 129—130 °C, and 184.21 g (19%)
of 2-chloro-1,1,2-trifluoro-3-isopropenylcyclobutane (2d)
((2S*,3R*)-2d : (2S*,3S*)-2d = 1.7 : 1), b.p. 139—142 °C.
Liquified products (103.3 g) collected in the trap cooled with dry
ice—ethanol mixture contained 82% of CTFE and 11% of
isoprene.
Similar copyrolysis procedure (440 °C) of CTFE and isoprene
1c (flow rate of each reactant 0.54 mol h–1) for 10 h and subse-
quent steam distillation of the crude pyrolysate gave 752.31 g of
a product mixture containing (GC and NMR spectroscopy data)

1,2-Difluorobenzenes
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 1, January, 2020
73
4.1% of isoprene 1c, 7.9% of cyclobutane 2c, 10.6% of cyclobut-
ane 2d, 60.9% of cyclohexenes 3c,d, 5.8% of difluorotoluenes
4b,c, and 10.7% (total) of unidentified products. Vacuum distil-
lation of this mixture afforded 407.8 g (40%) of a mixture of
cyclohexenes 3c,d (3c : 3d = 2.1 : 1), b.p. 84—88 °C (70 Torr).
Liquified products (116.2 g) collected in the trap cooled with dry
ice—ethanol mixture contained 81% of CTFE and 9% of isoprene.
Pyrolysis of 3-alkenyl-2-chloro-1,1,2-trifluorocyclobut-
anes 2a—d. 2-Chloro-1,1,2-trifluoro-3-vinylcyclobutane (2a)
((2S*,3S*)-2a : (2S*,3R*)-2a = 1 : 1) (460.3 g, 2.70 mol) at
a constant flow rate of 1.53 g min–1 and a gas flow of nitrogen
(220 mL min–1) were passed through a tubular reactor heated to
480 °C for 5 h. The pyrolysis products leaving the reactor were
cooled in a water condenser and then collected in two sequen-
tially connected traps cooled with ice—water mixture and dry
ice—ethanol mixture. Steam distillation and drying of the liquid
pyrolysate gave 363.1 g of a mixture containing 13.8% of cyclo-
butane 2a, 71.1% of cyclohexene 3a, 6.9% of difluorobenzene 4a,
0.7% of butadiene, and 7.5% of unidentified products. Vacuum
distillation of this mixture afforded 230.3 g (50%) of 4-chloro-
4,5,5-trifluorocyclohex-1-ene (3a), b.p. 83—85 °C (130 Torr).
Liquified products (65.4 g) collected in the trap cooled with
dry ice—ethanol mixture contained 69% of CTFE and 24% of
butadiene 1a.
Similar pyrolysis (480 °C) of cyclobutane 2b (a mixture of
four isomers: (2S*,3S*)- and (2S*,3R*)-3-chloro-1,1,2-trifluoro-
3-(E-prop-1-en-1-yl)cyclobutanes and (2S*,3S*)- and (2S*,3R*)-
3-chloro-1,1,2-trifluoro-3-(Z-prop-1-en-1-yl)cyclobutanes in
the ratio of 1.6 : 1.5 : 1 : 1) (199.2 g, 1.08 mol) at a constant flow
rate of 1.66 g min–1 in a flow of nitrogen (220 mL min–1) for
2 h gave 173.1 g of the liquid pyrolysate, steam distillation and
drying of which gave 156.1 g of a product mixture containing
19.2% of cyclobutanes 2b, 56.4% of cyclohexenes 3b, 6.3% of
difluorotoluene 4b, 2.7% of difluorotoluene 4c, 5.1% of penta-
diene 1b, and 10.3% (total) of unidentified products. Vacuum
distillation of this mixture afforded 75.96 g (38%) of cyclohexenes
3b (a mixture of cis-3b and trans-3b in the ratio of 1 : 1.4), b.p.
66—69 °C (44 Torr). Liquified products (18.1 g) collected in the
trap cooled with dry ice—ethanol mixture contained 81% of
CTFE and 6% of pentadiene 1b.
Similar pyrolysis (470 °C) of cyclobutane 2c (99.62 g,
0.540 mol) (flow rate 1.66 g min–1) in a flow of nitrogen
(220 mL min–1) for 1 h gave 90.32 g of the liquid pyrolysate, steam
distillation and drying of which gave 82.21 g of a product mixture
containing 12.1% of cyclobutane 2c, 67.9% of cyclohexene 3c,
6.1% of difluorotoluene 4c, 2.1% of difluorotoluene 4b, 1.8% of
isoprene, and 9.8% (total) of unidentified products. Vacuum
distillation of this mixture afforded 50.79 g (51%) of 4-chloro-
4,5,5-trifluoro-1-methylcyclohex-1-ene (3c), b.p. 85—87 °C
(70 Torr). Liquified products (7.9 g) collected in the trap cooled
with dry ice—ethanol mixture contained 79% of CTFE and 9%
of isoprene 1c.
Similar pyrolysis (475 °C) of cyclobutane 2d (99.63 g,
0.540 mol) at a constant flow rate of 1.66 g min–1 in a flow of
nitrogen (220 mL min–1) for 1 h gave 86.42 g of the liquid pyroly-
sate, which was steam distilled and dried to give 79.41 g of
a product mixture containing 13.7% of cyclobutane 2d, 67.8%
of cyclohexene 3d, 7.8% of difluorotoluene 4c, 1.9% of isoprene,
and 8.8% (total) of unidentified products. Vacuum distillation
of this mixture afforded 47.78 g (48%) of cyclohexene 3d, b.p.
85—87 °C (70 Torr). Liquified products (8.7 g) collected in the
trap cooled with dry ice—ethanol mixture contained 81% of
CTFE and 5% of isoprene 1c.
Similar pyrolysis (470 °C) of a 1.5 : 1 mixture of cyclobutanes
2c and 2d (199.26 g, 1.08 mol) at a constant flow rate of
1.66 g min–1 in a flow of nitrogen (220 mL min–1) for 2 h gave
174.8 g of the crude liquid pyrolysate, which was steam distilled
and dried to give 160.8 g of a product mixture containing 5.9%
of cyclobutane 2c, 6.5% of cyclobutane 2d, 68.2% of cyclohexenes
3c,d, 5.4% of difluorotoluene 4c, 2.3% of difluorotoluene 4d,
1.9% of isoprene, and 9.8% (total) of unidentified products.
Vacuum distillation of this mixture afforded 98.8 g (50%) of
a 1.9 : 1 mixture of cyclohexenes 3c and 3d, b.p. 84—86 °C
(70 Torr). Liquified products (15.2 g) collected in the trap cooled
with dry ice—ethanol mixture contained 81% of CTFE and 5%
of isoprene.
2-Chloro-1,1,2-trifluoro-3-vinylcyclobutane (2a)33,34 (a 1 : 1
mixture of (2S*,3R*)- and (2S*,3S*)-2-chloro-1,1,2-trifluoro-
3-vinylcyclobutanes). 1H NMR (CDCl3), δ: 2.20—2.93 (m, 2 H,
CH2); 3.17—3.48 (m, 1 H, CH); 5.18—5.45 (m, 2 H, C=CH2);
5.29—6.00 (m, 1 H, C=CH). 19F NMR (for (2S*,3S*)-2a)
(CDCl3), δ: –98.3, –117.1 (both br.d, 1 F each, CF2, J = 196 Hz);
–110.0 (br.s, 1 F, CFCl). 19F NMR (for (2S*,3R*)-2a) (CDCl3),
δ: –104.7, –109.1 (both br.d, 1 F each, CF2, J = 199 Hz); –134.1
(br.s, 1 F, CFCl)). MS, m/z (Irel (%)): 170 [M]+ (2), 135 (45),
106 (16), 54 (100), 53 (40).
2-Chloro-1,1,2-trifluoro-3-((Z)-prop-1-en-1-yl)cyclobutane
(Z-2b)25 (a 1 : 1 mixture of (2S*,3R*)-Z-2b and (2S*,3S*)-Z-2b).
1H NMR (CDCl3), δ: 1.71 (dd, 3 H, CH3, J = 5.0 Hz, J = 1.8 Hz);
2.08—2.37 (m, 2 H, CH2); 3.33—3.71 (m, 1 H, CH); 5.30—5.90
(m, 2 H, HC=CH). 19F NMR (for (2S*,3S*)-Z-2b) (CDCl3),
δ: –98.2, –117.8 (both br.d, 1 F each, CF2, J = 194 Hz); –108.9
(br.s, 1 F, CFCl). 19F NMR (for (2S*,3R*)-Z-2b) (CDCl3), δ:
–106.2, –108.0 (both br.d, 1 F each, CF2, J = 194 Hz); –134.5
(br.s, 1 F, CFCl). MS (for the mixture of Z-2b and E-2b), m/z
(Irel (%)): 184 [M]+ (2), 149 (42), 120 (18), 85 (32), 68 (100),
67 (44), 53 (18), 39 (19).
2-Chloro-1,1,2-trifluoro-3-((E)-prop-1-en-1-yl)cyclobutane
(E-2b)25 (a 1 : 1.1 mixture of (2S*,3R*)-E-2b and (2S*,3S*)-E-
2b). 1H NMR (CDCl3), δ: 1.76 (d, 3 H, CH3, J = 6.3 Hz);
2.38—2.95 (m, 2 H, CH2); 3.01—3.32 (m, 1 H, CH); 5.30—5.90
(m, 2 H, HC=CH). 19F NMR (for (2S*,3S*)-E-2b) (CDCl3),
δ: –98.9, –117.8 (both br.d, 1 F each, CF2, J = 194 Hz); –110.2
(br.s, 1 F, CFCl). 19F NMR (for (2S*,3R*)-E-2b) (CDCl3), δ:
–107.1, –108.7 (both br.d, 1 F each, CF2, J = 194 Hz); –134.9
(br.s, 1 F, CFCl). MS (for the mixture of Z-2b and E-2b), m/z
(Irel (%)): 184 [M]+ (2), 149 (42), 120 (18), 85 (32), 68 (100),
67 (44), 53 (18), 39 (19).
2-Chloro-1,1,2-trifluoro-3-methyl-3-vinylcyclobutane (2c)35
(a 1 : 1 mixture of (2S*,3R*)-2c and (2S*,3S*)-2c). 1H NMR
(CDCl3), δ: 1.35—1.45 (m, 3 H, CH3); 2.30—2.53 (m, 1 H,
CH2); 2.55—2.91 (m, 1 H, CH2); 5.08—5.37 (m, 2 H, =CH2);
5.92—6.12 (m, 1 H, =CH—). 19F NMR (for (2S*,3S*)-2c)
(CDCl3), δ: –98.8, –109.3 (both br.d, 1 F each, CF2, J = 202 Hz);
–123.5 (1 F, CF). 19F NMR (for (2S*,3R*)-2c) (CDCl3), δ:
–101.9, –107.8 (both br.d, 1 F each, CF2, J = 202 Hz); –126.7
(br.s, 1 F, CFCl). MS, m/z (Irel (%)): 184 [M]+ (2), 149 (17),
120 (22), 85 (27), 68 (100), 67 (63), 53 (28), 39 (26).
2-Chloro-1,1,2-trifluoro-3-isopropenylcyclobutane (2d)35
(a 1.7 : 1 mixture of (2S*,3R*)-2d and (2S*,3S*)-2d). 1H NMR
(CDCl3), δ: 1.87 (m, 3 H, CH3); 2.29—2.62 (m, 1 H, CH2);
2.63—2.84 (m, 1 H, CH2); 4.71—4.87 (m, 1 H, =CH2); 5.06—5.14

Volchkov et al.
74
Russ. Chem. Bull., Int. Ed., Vol. 69, No. 1, January, 2020
(m, 1 H, =CH2). 19F NMR (for (2S*,3S*)-2d) (CDCl3), δ:
–99.0, –119.0 (both br.d, 1 F each, CF2, J = 202 Hz); –108.8
(br.s, 1 F, CFCl). 19F NMR (for (2S*,3R*)-2d) (CDCl3), δ:
–107.7 (br.s, 2 F, CF2); –138.2 (br.s, 1 F, CFCl). MS, m/z
(Irel (%)): 184 [M]+ (2), 149 (18), 120 (24), 85 (28), 68 (100),
67 (66), 53 (30), 39 (27).
presence of TEBAC (1.0 g) gave 17.42 g of a product mixture
containing 85.9% of 3,4-difluorotoluene (4c) and 8.5% of
4-chloro-3-fluorotoluene (8c). Distillation afforded 14.03 g (83%)
of 3,4-difluorotoluene (4c), b.p. 123—124 °C.
Similar dehydrohalogenation of cyclohexene 3d (22.54 g,
0.122 mol) by treatment with 50% aqueous KOH (50.0 g) in the
presence of TEBAC (1.0 g) gave 15.96 g of a product mixture
containing 85.1% of 3,4-difluorotoluene (4c) and 9.1% of
3-chloro-4-fluorotoluene (8d). Distillation afforded 12.81 g (82%)
of 3,4-difluorotoluene (4c), b.p. 123—124 °C.
4-Chloro-4,5,5-trifluorocyclohex-1-ene (3a).19,25,36 B.p.
83—85 °C (130 Torr). 1H NMR (CDCl3), δ: 2.72—2.94 (m, 2 H,
CH2); 2.95—3.13 (m, 2 H, CH2); 5.53—5.72 (m, 2 H, HC=CH).
19F NMR (CDCl3), δ: –111.2, –113.4 (both br.d, 1 F each, CF2,
J = 245 Hz); –122.2 (br.s, 1 F, CFCl). MS, m/z (Irel (%)): 172
and 170 [M]+ (12 and 38), 135 (55), 134 (91), 115 (92), 106 (60),
95 (51), 90 (58), 84 (45), 57(37), 51(44), 39 (100).
Similar dehydrohalogenation of a mixture of cyclohexenes
3c,d (3c : 3d = 2.1 : 1) (293.31 g, 1.59 mol) by treatment with
50% aqueous KOH (640.0 g) in the presence of TEBAC (12.0 g)
gave 205.9 g of a product mixture containing 86.1% of 3,4-di-
fluorotoluene (4c), 6.2% of 4-chloro-3-fluorotoluene (8c), and
2.9% of 3-chloro-4-fluorotoluene (8d). Distillation afforded
170.42 g (84%) of 3,4-difluorotoluene (4c) and 16.82 g (7%)
of a 2.1 : 1 mixture of chlorofluorotoluenes 8c and 8d, b.p.
156—160 °C.
4-Chloro-4,5,5-trifluoro-3-methylcyclohex-2-ene (3b)19,25
(a 1 : 1.3 mixture of cis-3b and trans-3b). MS (a mixture of cis-3b
and trans-3b), m/z (Irel (%)): 186 and 184 [M]+ (5 and 16),
149 (100), 133 (12), 129 (22), 120 (22), 109 (18), 85 (22), 68 (20),
65 (16), 39 (12).
Major isomer. 1H NMR (CDCl3), δ: 1.31 (d, 3 H, CH3,
J = 6.4 Hz); 2.67—3.02 (m, 2 H, CH2); 3.03—3.25 (m, 1 H,
CH); 5.36—5.67 (m, 2 H, HC=CH). 19F NMR (CDCl3), δ:
–110.4, –115.6 (both br.d, 1 F each, CF2, J = 244 Hz); –132.4
(br.s, 1 F, CFCl).
1,2-Difluorobenzene (4a). 1H NMR (CDCl3), δ: 7.05—7.25
(m, 4 H, arom.). 19F NMR (CDCl3), δ: –137.5 (m, 2 F, arom.).
MS, m/z (Irel (%)): 114 [M]+ (100), 95 (7), 88 (30), 63 (35),
56 (17), 50 (14).
Minor isomer. 1H NMR (CDCl3), δ: 1.34 (d, 3 H, CH3,
J = 6.4 Hz); 2.67—3.02 (m, 2 H, CH2); 3.03—3.25 (m, 1 H,
CH); 5.36—5.67 (m, 2 H, HC=CH). 19F NMR (CDCl3), δ:
–108.0, –111.2 (both br.d, 1 F each, CF2, J = 244 Hz); –134.2
(br.s, 1 F, CFCl).
Spectral data of compound 4a are identical to those of a com-
mercially available sample of 1,2-difluorobenzene (Sigma-
Aldrich).
2,3-Difluorotoluene (4b).19,37 1H NMR (CDCl3), δ: 2.31
(br.s, 3 H, CH3); 6.83—7.10 (m, 3 H, Ar). 19F NMR (CDCl3),
δ: –139.1 (m, 1 F); –142.6 (m, 1 F). MS, m/z (Irel (%)):
128 [M]+ (58), 127 (100), 109 (7), 107 (8), 101 (10), 75 (6),
57 (6), 51 (6).
4-Chloro-4,5,5-trifluoro-1-methylcyclohex-1-ene (3c).19,25
1H NMR (CDCl3), δ: 1.75 (m, 3 H, CH3); 2.60—2.82 (m, 2 H,
CH2); 2.84—3.08 (m, 2 H, CH2); 5.24—5.34 (m, 1 H, =CH).
19F NMR (CDCl3), δ: –110.5, –112.7 (both br.d, 1 F each, CF2,
J = 246 Hz); –124.0 (br.s, 1 F, CFCl). MS, m/z (Irel (%)): 186
and 184 [M]+ (17 and 53), 149 (100), 133 (28), 129 (53), 109
(15), 85 (47), 68 (55).
3,4-Difluorotoluene (4c).19 1H NMR (CDCl3), δ: 2.32 (s, 3 H,
CH3); 6.85—7.12 (m, 3 H, Ar). 19F NMR (CDCl3), δ: –138.7
(m, 1 F); –143.0 (m, 1 F). MS, m/z (Irel (%)): 128 [M]+ (46),
127 (100), 109 (9), 107 (7), 101 (13), 75 (7), 57 (8), 51 (9).
Spectral data of compound 4a are identical to those of a com-
mercially available sample of 3,4-difluorotoluene (Sigma-
Aldrich).
5-Chloro-4,4,5-trifluoro-1-methylcyclohex-1-ene (3d).19,25
1H NMR (CDCl3), δ: 1.75 (m, 3 H, CH3); 2.63—2.85 (m, 2 H,
CH2); 2.86—3.04 (m, 2 H, CH2); 5.26—5.38 (m, 1 H, =CH).
19F NMR (CDCl3), δ: –111.8, –114.6 (both br.d, 1 F each, CF2,
J = 246 Hz); –122.4 (br.s, 1 F, CFCl). MS, m/z (Irel (%)): 186
and 184 [M]+ (19 and 58), 149 (100), 133 (32), 129 (57), 109
(16), 85 (48), 68 (57).
Water-alkaline aromatization of chlorotrifluorocyclohexenes
3a—d. A 50% aqueous KOH (392.0 g, 3.50 mol) was added to
a mixture of cyclohexene 3a (170.5 g, 1.0 mol) and TEBAC (7.0 g)
at 75—85 °C (oil bath) with stirring over 90 min, then the mixture
was stirred for 3 h at 85—95 °C. Steam distillation of the result-
ing mixture gave a mixture of organic products, which was dried
with CaCl2. The dried mixture of product (110.8 g) contained
86.1% of 1,2-difluorobenzene (4a) and 9.2% of 2-chloro-1-
fluorobenzene (8a). Distillation of this mixture afforded 94.91 g
(83%) of 1,2-difluorobenzene (4a), b.p. 92—92.5 °C, and 9.22 g
(7%) of chlorofluorobenzene 8a, b.p. 137—138 °C.
1-Chloro-2-fluorobenzene (8a).38 1H NMR (CDCl3), δ:
7.03—7.12 (m, 2 H, Ar); 7.17—7.24 (m, 1 H, Ar); 7.34—7.38
(m, 1 H, arom.). 19F NMR (CDCl3), δ: –109.7 (m, 1 F).
2-Chloro-3-fluorotoluene (8b).39 1H NMR (CDCl3), δ: 2.39
(s, 3 H, CH3); 6.89—7.08 (m, 3 H, Ar). 19F NMR (CDCl3), δ:
–113.8 (m, 1 F). MS, m/z (Irel (%)): 146 and 144 [M]+ (15 and
45), 109 (100), 107 (14), 83 (12).
4-Chloro-3-fluorotoluene (8c).14 1H NMR (CDCl3), δ: 2.21
(s, 3 H, CH3); 7.20—7.26 (m, 3 H, Ar). 19F NMR (CDCl3), δ:
–115.2 (m, 1 F). MS, m/z (Irel (%)): 146 and 144 [M]+ (13 and
42), 109 (100), 107 (13), 83 (11).
3-Chloro-4-fluorotoluene (8d).14,40 1H NMR (CDCl3), δ:
2.30 (s, 3 H, CH3); 6.99—7.20 (m, 3 H, Ar). 19F NMR (CDCl3),
δ: –119.6 (m, 1 F). MS, m/z (Irel (%)): 146 and 144 [M]+
(16 and 49), 109 (100), 107 (17), 83 (15).
Similar dehydrohalogenation of cyclohexene 3b (a 1 : 1.3
mixture of cis-3b and trans-3b) (243.93 g, 1.32 mol) by treatment
with 50% aqueous KOH (535.0 g) in the presence of TEBAC
(10.0 g) gave 170.17 g of a product mixture containing 85.1% of
2,3-difluorotoluene (4b) and 8.4% of 2-chloro-3-fluorotoluene
(8b). Distillation afforded 138.92 g (82%) of 2,3-difluorotoluene
(4b), b.p. 124—125 °C.
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