Mechanistic studies on fluorobenzene synthesis from 1,1-difluorocyclohexane via pd-catalyzed dehydrofluorodehydrogenation

Article abstract of DOI:10.1246/bcsj.20100270

The chemical reactivity and reaction mechanism of fluorobenzene synthesis via dehydrofluorodehydrogenation of 1,1-difluorocyclohexane was investigated. 1,1-Difluorocyclohexane reacted with molecular oxygen to give fluorobenzene in good yields in the presence of both Pd and metal fluoride catalysts. The reaction proceeded with dehydrofluorination of 1,1-difluorocyclohexane to yield 1-fluorocyclohexene as the sole intermediate species, followed by oxidative dehydrogenation. The present system offers a selective synthesis of fluorobenzene.

Full text of DOI:10.1246/bcsj.20100270

© 2011 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 84, No. 3, 333–340 (2011)
333
Mechanistic Studies on Fluorobenzene Synthesis from
1,1-Difluorocyclohexane via Pd-Catalyzed
Dehydrofluoro-Dehydrogenation
Masahiro Tojo,*1,2 Shinsuke Fukuoka,3 and Hiroshi Tsukube1
1Department of Chemistry, Graduate School of Science, Osaka City University,
Sugimoto, Sumiyoshi-ku, Osaka 558-8585
2Chemistry and Chemical Process Laboratory, Asahi KASEI Chemicals Corporation,
2767-11 Niihama, Kojima-Shionasu, Kurashiki, Okayama 711-8510
3New Business Development, Asahi KASEI Corporation,
1-105 Kanda Jinbocho, Chiyoda-ku, Tokyo 101-8101
Received September 21, 2010; E-mail: tojo.mb@om.asahi-kasei.co.jp
The chemical reactivity and reaction mechanism of fluorobenzene synthesis via dehydrofluoro-dehydrogenation of
1,1-difluorocyclohexane was investigated. 1,1-Difluorocyclohexane reacted with molecular oxygen to give fluorobenzene
in good yields in the presence of both Pd and metal fluoride catalysts. The reaction proceeded with dehydrofluorination
of 1,1-difluorocyclohexane to yield 1-fluorocyclohexene as the sole intermediate species, followed by oxidative
dehydrogenation. The present system offers a selective synthesis of fluorobenzene.
Fluoroaromatics are widely used in the synthesis of
pharmaceuticals,1 agrochemicals,2 functional organic materi-
als,3 and high-performance polymers.4 Fluorobenzene in
particular is a common starting material for commercial-scale
manufacturing processes. Although various synthetic methods
have been reported for fluorobenzene,5 most of them have
drawbacks as follows. The Schiemann reaction typically
involves unstable diazonium salts.5a,6 Nucleophilic displace-
ment of aryl chloride by fluoride is known to generate
chloride as waste.7 Direct fluorination of benzene using F2
and some metal fluorides exhibits poor selectivity.8 1-Alkyl-4-
fluoro-1,4-diazoniabicyclo[2.2.2]octane salts (Selectfluor·)
are applicable in fluorination of activated aromatics.8,9
Copper(II) fluoride reacts directly with benzene, and is
regenerated by treating the copper metal with hydrogen
fluoride (HF) under molecular oxygen,10 but its conversion is
less than 30%.
We have previously reported that 1,1-difluorocyclohexane
was converted to fluorobenzene by catalytic oxidative dehydro-
fluoro-dehydrogenation.16 Because 1,1-difluorocyclohexane is
easily synthesized from cyclohexanone by various meth-
ods,17,18 its dehydrofluoro-dehydrogenation can be an alter-
native synthesis of fluorobenzene. Although this method had
been reported earlier,16 the reaction mechanism had not yet
been discussed. Herein, we report the chemical reactivity and
reaction mechanism of the dehydrofluoro-dehydrogenation
of 1,1-difluorocyclohexane in the presence of catalyst. 1,1-
Difluorocyclohexane reacted with molecular oxygen to give
fluorobenzene in good yields in the presence of both Pd and
metal fluoride catalysts. It was proven that the reaction
proceeded with dehydrofluorination of 1,1-difluorocyclohexane
to yield 1-fluorocyclohexene as the sole intermediate species,
and subsequent oxidative dehydrogenation gave fluorobenzene.
Thus, this offers a selective synthesis of fluorobenzene.
Recently, transition-metal-promoted fluorinations have been
developed using electrophilic N-F reagents. Sanford and co-
workers11 reported a palladium-mediated fluorination of ar-
omatic C-H bonds. Ritter and co-workers12 published a
palladium-12a-12c or silver-mediated12d-12f fluorination of aryl
boronic acids and aryl stannanes. However, substrates are
limited to specific pyridine derivatives in the former reaction
and stoichiometric amounts of transition metal are necessary in
the latter reaction. More recently, Buchwald and co-workers13
achieved a palladium-catalyzed nucleophilic conversion of aryl
triflates into aryl fluorides using metal fluorides. Most recently,
Knochel and co-workers14 and Beller and co-workers15
reported an electrophilic fluorination of aryl bromides or
iodides via aryl magnesium reagent.
Results and Discussion
Oxidative Dehydrofluoro-Dehydrogenation of 1,1-Di-
fluorocyclohexane (1). We first characterized the catalytic
oxidative dehydrofluoro-dehydrogenation of 1,1-difluorocyclo-
hexane (1) in the presence of molecular oxygen as an oxidant.
In the formation of fluorobenzene (2) from 1, an effective
catalyst must promote both dehydrofluorination and dehydro-
genation. HF is formed as a result of dehydrofluorination, and
therefore the catalyst should be acid resistant. Combinations of
heterogeneous group VIII metals and metal fluorides were
chosen for these reasons,16 because the metal fluoride works
as a dehydrofluorination catalyst, and the group VIII metal
operates as a dehydrogenation catalyst. Gas-phase reaction of 1
Published on the web March 4, 2011; doi:10.1246/bcsj.20100270

334
Bull. Chem. Soc. Jpn. Vol. 84, No. 3 (2011)
PhF Synthesis from 1,1-Difluorocyclohexane
Table 1. Oxidative Dehydrofluoro-Dehydrogenation of 1,1-Difluorocyclohexane (1)a)
F
b)
F
F
O2 + N2
F
+
+
+
+
Catalyst
∆
5
1
2
3
4
6
Group VIII
metal
(wt %)d)
Metal
fluoride
(wt %)d)
Selectivityg)/%
Catalyst
activityh)
/mmol m¹2 h
Temperature Timee) Conversionf)
Entry
/°C
/h
/%
2
3
4
5
6
¹1
1
2
3
4
5
6
7
8
9
Pd-black (10)
Pt-black (10)
Ru-black (10)
Pd-black (10)
Pd-black (10)
Pd-black (10)
Pd-black (10)
Pd-black (10)
Pd-black (30)
Pd-black (60)
AlF3 (90)
AlF3 (90)
AlF3 (90)
FeF3 (90)
GaF3 (90)
AlF3 (90)
AlF3 (90)
AlF3 (90)
AlF3 (70)
AlF3 (40)
370
370
370
370
370
370
410
450
450
450
0.31
0.31
0.31
0.31
0.31
0.63
0.63
0.63
0.63
0.63
72
69
70
30
9
72
99
100
100
100
8
5
1
7
6
91
94
98
92
93
92
84
71
38
18
0.2
0.2
0.3
0.4
0.2
0.2
0.3
0.4
0.4
0.5
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.2
0.2
0.1
0.1
0.1
0.2
0.1
0.2
2.0
1.0
0.1
0.7
0.2
0.9
2.5
4.8
2.6
2.3
7
15
28
61
81
10
a) 8 g h¹1 (Entries 1-5) or 4 g h¹1 (Entries 6-10) of gaseous 1 was fed to a fixed bed flow reactor packed with the catalysts. b) Mixed
¹1 c)
¹1 c)
gas [O2: 20 cm3 min¹1 c); N2: 200 cm3 min
(Entries 1-5) or O2: 50 cm3 min¹1 c); N2: 450 cm3 min
(Entries 6-10)] was used.
c) Standard cubic centimeters per minute. d) Total amount of catalyst was 2.50 g. e) Residence time was calculated from a reciprocal of
WHSV (weight hourly space velocity). f) Determined by gas-liquid chromatography. g) Based on 1. h) Yield of 2 per unit metal
¹1
surface areai) per hour. i) Metal surface area: Pt-black 30 m2 g¹1; Ru-black 90 m2 g¹1; Pd-black 25 m2 g
.
with molecular oxygen was performed under atmospheric
pressure over a fixed bed flow reactor packed with a mixture of
a group VIII metal and metal fluoride catalysts as described
earlier.16 Reaction conditions and selected results are summa-
rized in Table 1.
When the catalyst activities (yield of 2 per unit metal surface
per hour) with AlF3 were compared (Entries 1-3), Pd-black
exhibited the highest activity (2.0 mmol m¹2 h¹1). Although the
major product was 1-fluorocyclohexene (3) (91-98% selectiv-
ity), this dehydrofluorination catalyst also produced 2 (1-8%
selectivity) and benzene (4), cyclohexene (5), and cyclohexane
(6) (less than 1% each). Among the dehydrofluorination
catalysts (Entries 1, 4, and 5), AlF3, the most acidic Lewis
acid, was the most active catalyst in the presence of Pd-black.
Table 1 also (Entries 6-8) shows that conversion of 1,
selectivity of 2, and catalyst activity increased with higher
temperature (conversion of 1: 72-100%; selectivity of 2: 7-
28%; catalyst activity: 0.9-4.8 mmol m¹2 h¹1). A relatively
higher selectivity of 2 (28%) was observed at 450 °C (Entry 8).
The increase in the ratio of Pd-black catalyst to AlF3 catalyst
enhanced the yield of 2 (28-81%, Entries 8-10), whereas the
conversion of 1 remained 100%. Thus, a smaller amount of
dehydrofluorination catalyst (AlF3) is sufficient because the
dehydrogenation catalyst (Pd-black) catalyzes the rate-control-
ling step.
Figure 1 indicates the time course of dehydrofluoro-de-
hydrogenation of 1. Catalysts and reaction temperature were
identical to those of Entry 10 in Table 1. A range of the
residence time (from 0.078 to 1.25 h) was determined by
varying the feed rate of the inlet gas (the mixture of 1, O2, and
N2). Because 3 (symbol ) increased with decreasing of 1
(symbol ), and 2 (symbol ) increased with decreasing of 3,
simple consecutive first-order kinetics of 2 from 1 via 3 were
assumed. The rate equations are
Figure 1. Time courses of oxidative dehydrofluoro-de-
hydrogenation of 1,1-difluorocyclohexane (1). Gaseous 1
was fed to a fixed bed flow reactor packed with catalyst
(mixture of 1.5 g of Pd-black and 1.0 g of AlF3) under
mixed gas (O2: 50 cm3 min¹1; N2: 450 cm3 min¹1) at
450 °C, and residence time was calculated from
a
reciprocal of WHSV (weight hourly space velocity).
Symbols ( , , and ) are experimental data and
calculated lines are based on the assumption that 1 yields
2 via 3 consecutively.
d½1ꢀ=dt ¼ ꢁk1½1ꢀ
d½3ꢀ=dt ¼ k1½1ꢀ ꢁ k2½3ꢀ
d½2ꢀ=dt ¼ k2½3ꢀ
ð1Þ
ð2Þ
ð3Þ
where [1], [2], and [3] are concentrations in mole fractions of 1,
2, and 3, respectively. The symbols k1 and k2 are rate constants
of the reaction from 1 to 3 and 3 to 2, which were obtained by

M. Tojo et al.
Bull. Chem. Soc. Jpn. Vol. 84, No. 3 (2011)
335
F
b)
9
10
c)
a)
d)
Reactant
Intermediate
F
F
b), e)
F
F
1
3
4
5
6
By-products
a)
F
a), e)
a), e)
F
b)
F
High reactive intermediates
11
7
8
a)
a), e)
a), e)
Main product
F
F
b)
F
2
12
Scheme 1. Possible reaction sequence of 2 formation by dehydrofluoro-dehydrogenation of 1. Conditions: a) Oxidative
dehydrogenation. b) Dehydrofluorination. c) Isomerization. d) Disproportionation or simple dehydrogenation. e) Bold lines are
possible main paths.
curve fitting of the experimental data.19 The calculated lines
based on this assumption were in good agreement with the
experimental data, supporting that 3 is an intermediate to 2
from 1. The fitted rate constant k1 (12.1 h¹1) was larger than k2
(3.3 h¹1), showing that the dehydrofluorination is faster than
oxidative dehydrogenation under the present conditions.
dehydrofluorinated to yield 7 and 2, respectively. The reaction
steps including 11 and 12 as shown in Scheme 1 are discussed
below.
Dehydrofluorination of 1,1-Difluorocyclohexane (1). We
conducted gas-phase dehydrofluorination of 1 in order to
characterize the reaction path from 1 to 3 as shown in
Scheme 1. Although gas-phase heterogeneous dehydrofluori-
Scheme 1 shows a possible reaction sequence including
several dehydrofluorination and dehydrogenation pathways. At
first, 1 yields 3 as shown in Figure 1. 2-Fluorocyclohexa-1,3-
diene (7) or 1-fluorocyclohexa-1,3-diene (8) must be consec-
utively formed by dehydrogenation of 3, but were not
observed. The conjugated dienes 7 and 8 do not desorb and
have high reactivities for further dehydrogenation to 2. Besides
fluorine-containing compounds 2 and 3, small amounts of
cyclic hydrocarbons 4, 5, and 6 are formed. It was confirmed
that independently synthesized 920 easily dehydrofluorinates
to yield reactive cyclohexa-1,3-diene (10), which yields 4, 5,
and 6 under oxidative conditions. Considering that the bond
between the sp2-carbon and fluorine atom is stable, this
suggests that 3 isomerizes to 3-fluorocyclohexene (9). When
the dehydrofluorination and dehydrogenation catalysts are
mixed before use (Table 1), there is a possibility that
dehydrogenation occurs prior to dehydrofluorination. The
dehydrogenated product 3,3-difluorocyclohexene (11) might
be further dehydrogenated to yield 5,5-difluorocyclohexa-
1,3-diene (12). Both allyl difluorides 11 and 12 could be
21a
nation of 1 has been reported before using Al2O3 or metal
fluorides21b as catalysts, no detailed data was published. The
reaction was carried out under atmospheric pressure over a
fixed bed flow reactor packed with AlF3. Detailed conditions
and selected results are summarized in Table 2. Intermediate 3
was obtained as the single product only with AlF3 (all entries).
Because the dehydrofluorinated product 10 and further dis-
proportionated products 4, 5, and 6 were not observed at all,
it is evident that the Pd-black catalyzed an isomerization
(Table 1). The activation energy Ea of the dehydrofluorination
of 2, determined by Arrhenius plot (Entries 2a-2d), was
136 kJ mol¹1, indicating that a high reaction temperature of up
to 450 °C is necessary to attain the high conversion of 1.
Oxidative Dehydrogenation of Cyclohexenes.
The
reactivities of fluorocyclohexenes 3 and 9 were examined in
order to understand the reaction path from 3 to 2 as shown in
Scheme 1. This reaction had been reported earlier,22 but metal
fluorides were not employed as catalysts. The oxidative
dehydrogenation of fluorocyclohexenes was carried out in a

336
Bull. Chem. Soc. Jpn. Vol. 84, No. 3 (2011)
PhF Synthesis from 1,1-Difluorocyclohexane
Table 2. Dehydrofluorination of 1 with AlF3 Catalysta)
F
F
F
AlF3
+
HF
N2, ∆
1
3
Selectivityd)/%
e)
f)
Temperature
Timeb)
/h
Conversionc)
/%
k1
/h
Ea
Af)
/h
Entry
¹1
¹1
¹1
/°C
/kJ mol
2
3
4
5
6
1
450
400
380
360
340
0.63
100
19.8
8.0
3.7
2.0
ND
ND
ND
ND
ND
>99
>99
>99
>99
>99
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
ND
®
®
®
9
2a
2b
2c
2d
0.078
0.078
0.078
0.078
2.83
1.07
0.48
0.26
>
=
136
9.3 © 1010
>
;
a) 4 g h¹1 (Entry 1) or 32 g h¹1 (Entries 2a-2d) of gaseous 1 and N2 [200 cm3 min¹1 (Entry 1) or 500 cm3 min¹1 (Entries 2a-2d)] were
fed to a fixed bed flow reactor packed with AlF3 (2.5 g). b) Residence time was calculated from a reciprocal of WHSV. c) Determined
by gas-liquid chromatography. d) Based on 1. ND: Not detected. e) Calculated from the integral representation of the first-order
reaction rate: k1 = ¹ln([1]/[1]0)/t. f) Activation energy Ea and frequency factor A were determined by Arrhenius plot.
Table 3. Oxidative Dehydrogenation of Fluorocyclohexenes with/without Dehydrofluorination Catalysta)
F
b)
F
O2 + N2
+
+
+
Pd/Support
2
4
5
6
∆, 0.63 hc)
1-Fluorocyclohexene (3)
3-Fluorocyclohexene (9)
Selectivityf)/%
Pdd)
(wt %)
Supportd)
(wt %)
Temperature
Conversione)
/%
Entry
Substrate
/°C
2
4
5
6
1
2
3
4
5
3
3
3
3
9
Pd-black (60)
Pd-black (60)
Pd (5)
Pd-black (60)
Pd-black (60)
AlF3 (40)
AlF3 (40)
SiO2 (95)
Quartz (40)
AlF3 (40)
370
200
200
200
200
100
34
96
51
100
98
98
81
98
1.5
1.5
14
1
99
0
0
2
0
0
0.4
0.3
3
0.6
0.2
0.6
¹1
a) 3.3 g h of gaseous 3 or 9 were fed to a fixed bed flow reactor packed with catalyst. b) Mixed gas (O2: 50 cm3 min¹1; N2:
450 cm3 min¹1) was used. c) Residence time was calculated from a reciprocal of WHSV. d) Mixed catalysts (Pd catalyst and support)
were used in Entries 1, 2, 4, and 5, and SiO2-supported Pd was used in Entry 3; total amount of catalysts was 2.5 g. e) Determined by
¹1
gas-liquid chromatography. f) Based on 1. g) Yield of 2 per unit metal surface areah) per hour. h) Metal surface area: Pd-black 25 m2 g
¹1
and Pd-SiO2 100 m2 g
.
similar manner as described for Entry 1 of Table 1, except 3 or
9 was used instead of 1.
steps relating to the formation of by-products (3 to 9, and 9 to 4
via 10) were catalyzed by Pd-black.
Table 3 shows that the conversion of 3 was 100% and
selectivity of 2 was 98% at 370 °C (Entry 1), but the conversion
of 3 was suppressed at 200 °C (34%, Entry 2). When Pd/SiO2
was employed, high conversion (96%) but low selectivity of 2
(81%) were observed (Entry 3). Because this is a common
catalyst for dehydrogenation, the acidity of the SiO2 might
affect the reactivity of the palladium metal. Indeed, an inactive
quartz support showed the same selectivity (98%) as that of
AlF3 at higher conversion (51%) in Entry 4. These results
suggest that AlF3 did not affect the selectivity of formation of
2 but somewhat affected the conversion of 3. When allyl
monofluoride 9, a probable intermediate to 4, 5, and 6, was used
instead of 3, 4 was mainly produced (99% selectivity) and only
a small amount of 2 was obtained (0.6% selectivity) (Entry 5).
Thus, 9 was found to be a precursor of 4 and Pd-black worked
as a dehydrogenation catalyst. As described above, the Pd-black
also worked as an isomerization catalyst of 3. Thus, the main
In comparing Entry 10 in Table 1 with Entry 1 in Table 3,
the former gave a lower yield of 2 (81%) at 450 °C than the
latter (98% yield) at 370 °C. Even if there might be some time-
lag in the reaction of Entry 10, the formation rate of 2 from 1 at
450 °C seems lower than that from 3 at 370 °C. Because the
former involved HF, the reaction kinetics of the oxidative
dehydrogenation of 3 were evaluated in order to confirm that
an effect from HF exists. Figure 2 illustrates the temperature
dependency of the reaction rate of oxidative dehydrogenation
of 3 with (symbol ) and without (symbol ) HF. The
Arrhenius plot based on the assumption of first-order kinetics
of 2 formation gave reaction rate constants k2 for each [with
HF: k2 = 2.06 © 104 exp(¹50000/RT); without HF: k2 =
3.42 © 104 exp(¹43000/RT)]. At 250 °C, the reaction rate in
the presence of HF (k2 = 0.21 h¹1) is 8 times slower than that in
the absence of HF (k2 = 1.73 h¹1). This suggests that the
activity of the Pd catalyst is somewhat affected by HF, e.g., HF

M. Tojo et al.
Bull. Chem. Soc. Jpn. Vol. 84, No. 3 (2011)
337
Scheme 2. Oxidative dehydrogenation of 1 without dehy-
drofluorination catalyst.
Effect of Catalyst Configuration. Because the dehydro-
genation of 1 is much more difficult than dehydrofluorination,
as mentioned above, the main pathway of the dehydrofluoro-
dehydrogenation of 1 should first experience dehydrofluorina-
tion of 1 to 3, followed by dehydrogenation of 3 to 2. In
Table 4, when the dehydrofluorination and dehydrogenation
catalysts were added separately in this order along the reaction
gas flow, this was indicated as “separated catalyst.” When both
catalysts were added, this was indicated as “mixed catalyst.”
Table 4 shows that the separated catalyst configuration showed
lower selectivity of 2 with larger amounts of by-products 4 and
6 (Entry 2) than the mixed catalyst configuration (Entry 1). The
concentration of 3 in the mixed catalyst is lower than that in the
separated catalyst, because the formed 3 immediately under-
goes dehydrogenation in the mixed catalyst. In the separated
catalyst configuration, formed 3 is accumulated during de-
hydrofluorination and is exposed all at once at its highest
concentration to the Pd catalyst, causing by-product formation.
Figure 2. Temperature dependency of the reaction rate of
oxidative dehydrogenation of 3. 26.7 g h of gaseous 3
¹1
Conclusion
was fed to a fixed bed flow reactor packed with catalyst
(2.5 g) under mixed gas (O2: 50 cm3 min¹1; N2: 450
cm3 min¹1) in the absence (symbol )/presence (symbol
) of HF at 140 to 350 °C. Residence time calculated from
a reciprocal of WHSV was 0.078 h. Activation energy Ea
of the dehydrofluorination of 3 was determined by
Arrhenius plot (first-order kinetics of 3 to 2 was assumed).
We have described the chemical reactivity and reaction
mechanism of the one-step synthesis of fluorobenzene (2)
by dehydrofluoro-dehydrogenation of 1,1-difluorocyclohexane
(1). gem-Difluoride 1 reacted with molecular oxygen to give 2
in good yields in the gas phase in the presence of Pd and metal
fluoride catalysts. Each possible reaction pathway was con-
ducted separately to elucidate the reaction mechanism, showing
that dehydrofluorination and dehydrogenation proceeded con-
secutively via 1-fluorocyclohexene (3). Examination of the
catalyst configuration showed that the dehydrofluorination and
dehydrogenation catalysts should be mixed to avoid lowering
the selectivity resulting from a high concentration of inter-
mediate 3. It was also found that the formed HF suppressed
the dehydrogenation to some extent, though a high yield of 2
was attained by increasing both the reaction temperature and
residence time. Because 1,1-difluorocyclohexane is easily
synthesized from cyclohexanone,17 its dehydrofluoro-dehydro-
genation is an alternative synthesis of fluorobenzene. From the
viewpoint of industrial production, it offers a practical syn-
thesis of fluorobenzene compared to direct fluorination of
benzene and homogeneous-metal-complex-mediated fluorina-
tion of benzene derivatives. The present system exhibits high
selectivity without any active electrophilic N-F reagent and/or
highly specialized metal complexes. Furthermore, this is a
clean reaction system, in which only water and recyclable HF
are formed as by-products.
could adsorb on Pd-black and suppress the activity of active
sites by surface-coating. Therefore, it is necessary to increase
the reaction temperature to 450 °C and extend the residence
time in order to achieve a high yield of 2 (Entry 10 of Table 1).
Oxidative Dehydrogenation of 1,1-Difluorocyclohexane (1).
In order to examine the possibility of the pathway via 11
in Scheme 1, gem-difluoride 1 was reacted using Pd-black
catalyst without AlF3 catalyst (Scheme 2). However, no
reaction proceeded, proving the absence of the pathway via
11 or 12. Because 3 was dehydrogenated to yield 2 even at
lower temperature (200 °C in Entry 4 of Table 3), it follows
that 1 has low reactivity against dehydrogenation. The HOMO
energy levels of the substrates were calculated, showing that
the HOMO energy of 1 (¹11.8 eV) is lower than that of 3
(¹9.8 eV). This supports that 1 is more stable than 3 against
dehydrogenation. It has become apparent that 1 can yield 2
only via reactive intermediate 3. The HOMO energy level of
unsubstituted cyclohexane 6 (¹11.2 eV) is considerably higher
than that of 1. This is in agreement with the fact that 6 is known
to dehydrogenate to benzene 4.23 The origin of the lower
HOMO energy level of 1 is derived from the lower atomic
orbital energy level of the fluorine’s 2p orbital (¹18.6 eV)
compared to that of the proton’s 1s orbital (¹13.6 eV).24
Experimental
General. Unless otherwise noted, chemical reagents were
purchased from commercial sources and used without further

338
Bull. Chem. Soc. Jpn. Vol. 84, No. 3 (2011)
PhF Synthesis from 1,1-Difluorocyclohexane
Table 4. Oxidative Dehydrofluoro-Dehydrogenation of 1: Effect of Catalyst Configurationa)
Catalyst configuration
Catalystb) (zone-A)c) Catalystb) (zone-B)c)
Mixture of AlF3 (1.0 g) and Pd-black (1.5 g)
AlF3 (1.0 g) Pd-black (1.5 g)
Selectivitye)/%
Conversiond)
/%
Entry
2
3
4
5
6
1f)
2
100
100
81
76
18
15
0.5
6
0.1
0.3
0.2
2
a) Gaseous 1 (4 g) and mixed gas (O2: 50 cm3 min¹1; N2: 450 cm3 min¹1) were fed to a fixed bed flow reactor packed
with catalyst; residence time calculated from a reciprocal of WHSV was 0.63 h; reaction temperature was 450 °C. b)
Total amount of catalyst was 2.50 g. c) Catalyst bed was divided into 2 zones, zone-A and zone-B, in this order along
the reaction gas flow. d) Determined by gas-liquid chromatography. e) Based on 1. f) Identical to Entry 10 of Table 1.
treatment. Group VIII metal catalysts were purchased from
N.E. Chemcat Corporation. Metal surface areas of catalysts
equipped with a mechanical stirrer and a condenser. The
mixture was stirred at 150 °C for 1.5 h, followed by vacuum
distillation. The distillate was redistilled under reduced
pressure to give trans-2-fluorocyclohexanol in 69% yield. Bp
77-78 °C/22 mmHg (lit.27 bp 68-69 °C/14 mmHg), mp 19-
¹1
¹1
were: Pt-black 30 m2 g
; ; Pd-black
Ru-black 90 m2 g
25 m2 g¹1; Pd-SiO2 100 m2 g¹1. The unit of gas flow rate was
standard cubic centimeters per minute (cm3 min¹1). Quantita-
tive analysis was carried out on a gas chromatograph with a
FID detector. The chemical structure of each product was
identified by a combination of GC-MS spectroscopy (Hewlett
1
20 °C (lit.21 19-20 °C). H NMR (270 MHz, CCl4): ¤ 0.6-2.4
(m, 8H), 3.33 (s, 1H), 3.2-4.8 (m, 2H). To a mixture of PBr3
(0.9 mol) and NaBr (0.72 mol), trans-2-fluorocyclohexanol
(0.9 mol) was added with stirring at 140 °C. After stirring at
140 °C for 5 h, the reaction mixture was poured into ice water
and worked up as described above. The crude product was
distilled under reduced pressure to give cis-1-bromo-2-fluoro-
cyclohexane (14) in 46% yield. Colorless liquid, bp 68-70 °C/
14 mmHg (lit.27 bp 78 °C/16 mmHg). 1H NMR (270 MHz,
CCl4): ¤ 1.0-2.6 (m, 8H), 3.8-5.1 (m, 2H). To the magnetically
stirred solution of tert-BuOK (0.25 mol) and tert-BuOH (300
mL), 14 (0.25 mol) was added slowly at room temperature
under nitrogen atmosphere, and the mixture was stirred at 70 °C
for 4 h. The reaction mixture was worked up as described
above. The crude product was distilled under atmospheric
pressure to give 3 in 80% yield. Bp 95-96 °C/760 mmHg
(lit.27 bp 96 °C/760 mmHg). The obtained 1 had an identical
1H NMR spectrum to that reported.25c,26
1
Packard HP-5971 or Hitachi M-80) and H NMR spectroscopy
(JEOL GX-270).
Synthetic Procedure.
1,1-Difluorocyclohexane (1):
Compound 1 was synthesized from cyclohexanone via 1,1-
bis(trifluoroacetoxy)cyclohexane (13) according to literature
procedures:17g Colorless liquid, bp 99-101 °C/760 mmHg
(lit.25b 99-100 °C/760 mmHg). 1H NMR (270 MHz, CDCl3):
¤ 1.9-2.3 (m, 10H). MS (EI): m/z 120 (M+, 9%), 100 (63), 80
(12), 57 (98), 41 (100).
1-Fluorocyclohexene (3) (Method A: Dehydrofluorina-
tion of 1): Authentic sample 3 was synthesized from 1.25 To a
magnetically stirred solution of tert-BuOK (0.3 mol) and 1,2-
dimethoxyethane (200 mL), 1 (0.2 mol) was added slowly at
room temperature under nitrogen atmosphere, and the mixture
was stirred under reflux (85 °C) for 12 h. After three quarters
of the solvent were evaporated under reduced pressure (550
mmHg) at an oil bath temperature of 90 °C, the reaction
mixture was poured into a mixture of ice and saturated aq.
NaHCO3. The resulting mixture was extracted five times with
diethyl ether. The combined extract was washed with water,
dried over MgSO4, and the solvent was evaporated. The crude
product was distilled under atmospheric pressure to give 3:25c,26
yield 17.4 g (87%). Colorless liquid, bp 95-96 °C/760 mmHg
(lit.26 95-96 °C/760 mmHg). MS (EI): m/z 100 (M+, 47%).
1H NMR (270 MHz, CCl4): ¤ 1.7-2.0 (m, 4H), 2.1-2.4 (m, 4H),
5.1 (d, J = 17.3 Hz, 1H).
3-Fluorocyclohexene (9):20
To diethylaminosulfur tri-
fluoride (=(diethylamino)trifluoro--4-sulfane, DAST, 0.05
mol) in a 50-mL polyethylene bottle cooled at ¹50 °C, 2-
cyclohexen-1-ol (0.05 mol) was added slowly at ¹50 °C with
stirring under nitrogen atmosphere, and the mixture was further
stirred for 3 h while warming to room temperature. The reaction
mixture was poured into a mixture of ice and saturated aq.
NaHCO3. The upper layer was separated, washed with ice
water, and dried over MgSO4 in a refrigerator to give crude 9
1
in 63% yield. H NMR (270 MHz, CCl4): ¤ 1.5-2.2 (m, 2H),
4.9 (m, 1H), 5.8 (m, 1H), 6.0 (m, 1H). The obtained product
decomposed slowly at room temperature20 to give HF and 1,3-
cyclohexadiene (10), which was identified spectroscopically.
Caution: Because HF is corrosive, the reaction mixture
containing HF should be handled in a well ventilated hood with
protection.
1-Fluorocyclohexene (3) (Method B: Dehydrobromina-
tion of cis-1-Bromo-2-fluorocyclohexane (14)):
Another
authentic sample 3 was synthesized according to literature
procedures:26,27 Cyclohexene oxide (1.22 mol), KHF2 (1.81
mol), and diethylene glycol (230 g) were mixed in a 1-L flask

M. Tojo et al.
Bull. Chem. Soc. Jpn. Vol. 84, No. 3 (2011)
339
Catalytic Reaction. Conversion of 1 to 2 by Oxidative
Dehydrofluoro-Dehydrogenation (Table 1, Figure 1): The
Group VIII metal (Pd-black, Pt-black, or Ru-black) and metal
fluoride (AlF3, FeF3, or GaF3) were mixed in advance. The
mixed catalyst (2.5 g) was packed in a fixed bed flow reactor.
Conversion of 1 to 2 by Oxidative Dehydrogenation
(Entry 2 of Table 4): The catalyst bed of the fixed bed flow
reactor was divided into two zones, zone-A and zone-B, in this
order along the reaction gas flow. AlF3 (1.0 g) was placed at
zone-A and Pd-black (1.5 g) was placed at zone-B. Compound
1 (4 g h¹1) was treated in a similar manner as above. Reaction
temperature was 450 °C and residence time was 0.63 h. The
reaction mixture was analyzed in the same manner as described
above.
To the reactor, the mixed gas [O2: 20 cm3 min¹1; N2: 200
¹1
cm3 min
(Entries 1-5) or O2: 50 cm3 min¹1; N2: 450
¹1
cm3 min (Entries 6-10)], which was used as the carrier gas
with oxidant, was fed. After the reactor was heated to the
desired temperature, gaseous 1 was fed to the reactor.
Residence time calculated from a reciprocal of WHSV (weight
hourly space velocity) was 0.31 or 0.63 h. The reaction mixture
gas, which contained HF, water, and organic compounds, was
cooled and collected into a mixture of ice and saturated aq.
NaHCO3. After the resulting mixture was extracted with
diethyl ether, the combined extracts were washed with water,
dried over MgSO4, and the solvent was evaporated. The crude
products were analyzed with toluene as an internal standard
using gas-liquid chromatography. The yields of 2-6 were based
on converted 1. Yields of 2 per unit metal surface area per hour
were calculated using the metal surface area. Products 2 and 3
were separated by preparative gas-liquid chromatography. All
products 2-6 were characterized spectroscopically and showed
Computational Method.
MOPAC 200228 in CS
ChemBio3D Ultra (ver. 11.0)29 was used to compute the
HOMO energy levels of 1, 3, and 6. The PM3 method was
selected in MOPAC.
References
1
a) S. Purser, P. R. Moore, S. Swallow, V. Gouverneur,
Chem. Soc. Rev. 2008, 37, 320. b) K. Müller, C. Faeh, F.
Diederich, Science 2007, 317, 1881. c) K. Uneyama, Organo-
fluorine Chemistry, Blackwell, Oxford, 2006, pp. 206-222. d) T.
Itoh, in Fluorine in Medicinal Chemistry and Chemical Biology,
ed. by I. Ojima, Wiley-Blackwell, London, 2009, pp. 313-315.
e) T. Itoh, in Current Fluoroorganic Chemistry: New Synthetic
Directions, Technologies, Materials, and Biological Applications
(ACS Symposium Series 949), ed. by V. A. Soloshonok, K.
Mikami, T. Yamazaki, J. T. Welch, J. F. Honek, American
Chemical Society, Washington, 2007, pp. 352-362. doi:10.1021/
bk-2007-0949.ch021
1
identical MS and H NMR spectra to the commercial reagents
(2 and 4-6) and 3 synthesized above.
Conversion of 1 to 3 by Dehydrofluorination (Table 2):
AlF3 (2.5 g) was packed in a fixed bed flow reactor instead of
mixed catalyst. N2 (500 cm3 min¹1) was fed to the reactor
instead of mixed O2/N2 gas. Compound 1 (4-32 g h¹1) was
treated in a similar manner as above except for the elimination
of dehydrofluorination catalyst and oxygen. Reaction temper-
ature was 340-450 °C and residence time was 0.63 h.
Conversion of Fluorocyclohexenes (3 and 9) by Oxidative
Dehydrogenation (Table 3): To a reactor, the mixed gas (O2:
50 cm3 min¹1; N2: 450 cm3 min¹1) was fed. After the reactor
was heated to 200 °C, 3.3 g h¹1 of gaseous 3 or 9 were fed to a
fixed bed flow reactor packed with catalyst [a mixture of a Pd
catalyst and a support (Entries 1, 2, 4, or 5) or Pd-supported
SiO2 (Entry 3); total amount of catalyst was 2.5 g]. Residence
time was 0.63 h.
2
D. Cartwright, Organofluorine Chemistry: Principles and
Commercial Applications, ed. by R. E. Banks, B. E. Smart, J. C.
Tatlow, Plenum Press, New York, 1994, pp. 237-262.
3
a) S. Singh, Liquid Crystals: Fundamentals, World Scien-
tific Pub., Singapore, 2002, pp. 92-173. b) T. Itoh, M. Kanbara, M.
Ohashi, S. Hayase, M. Kawatsura, T. Kato, K. Miyazawa, Y.
Takagi, H. Uno, J. Fluorine Chem. 2007, 128, 1112.
4
R. J. Cotter, Engineering Plastics: A Handbook of Poly-
arylethers, Gordon and Breach Science Pub., Basel, 1994, pp. 1-
52.
5
a) J. H. Clark, D. Wails, T. W. Bastock, Aromatic
Fluorination, CRC Press, Florida, 1996, pp. 1-17. b) J. S.
Moilliet, in Organofluorine Chemistry: Principles and Commer-
cial Applications, ed. by R. E. Banks, B. E. Smart, J. C. Tatlow,
Plenum Press, New York, 1994, pp. 195-220.
Conversion of 3 to 2 by Oxidative Dehydrogenation
¹1
6
7
H. Suschitzky, Adv. Fluorine Chem. 1965, 4, 1.
J. H. Clark, D. Wails, T. W. Bastock, Aromatic Fluorina-
with/without HF (Figure 2):
Without HF: 26.7 g h of
gaseous 3 was fed to a fixed bed flow reactor packed with
catalyst (2.5 g) under mixed gas (O2: 50 cm3 min¹1; N2: 450
cm3 min¹1) at 140-350 °C, and residence time was 0.078 h.
With HF: in the experiment (Symbol in Figure 2), 32 g h¹1 of
gaseous 1 was fed to a fixed bed flow reactor packed with AlF3
(2.5 g) and heated at 450 °C. The reaction mixture gas, which
contained HF and 3, was fed as 3 accompanied by HF.
Oxidative Dehydrogenation of 1 (Scheme 2): 2.5 g of a
mixture of Pd-black (60%) and quartz (40%) was packed in a
fixed bed flow reactor. Mixed gas (O2: 50 cm3 min¹1; N2:
450 cm3 min¹1) was fed to the reactor. The compound 1
(4 g h¹1) was treated in a similar manner as above except for
the elimination of the dehydrofluorination catalyst. Reaction
temperature was 450 °C and residence time was 0.63 h. The
reaction mixture was analyzed in the same manner as
described above. However, it was confirmed that no reaction
proceeded.
tion, CRC Press, Florida, 1996, pp. 19-55.
J. H. Clark, D. Wails, T. W. Bastock, Aromatic Fluorina-
tion, CRC Press, Florida, 1996, pp. 69-88.
a) R. E. Banks, S. N. Mohialdin-Khaffaf, G. S. Lal, I.
Sharif, R. G. Syvret, J. Chem. Soc., Chem. Commun. 1992, 595.
b) Selectfluor·: trademark of Airproducts and Chemicals, Inc.
10 a) M. A. Subramanian, L. E. Manzer, Science 2002, 297,
1665. b) M. A. Subramanian, T. G. Calvarese, Adv. Fluorine Sci.
2006, 2, 203.
8
9
11 K. L. Hull, W. Q. Anani, M. S. Sanford, J. Am. Chem. Soc.
2006, 128, 7134.
12 a) T. Furuya, H. M. Kaiser, T. Ritter, Angew. Chem., Int. Ed.
2008, 47, 5993. b) T. Furuya, T. Ritter, J. Am. Chem. Soc. 2008,
130, 10060. c) T. Furuya, D. Benitez, E. Tkatchouk, A. E. Strom,
P. Tang, W. A. Goddard, III, T. Ritter, J. Am. Chem. Soc. 2010,
132, 5922. d) T. Furuya, A. E. Strom, T. Ritter, J. Am. Chem. Soc.
2009, 131, 1662. e) T. Furuya, T. Ritter, Org. Lett. 2009, 11, 2860.

340
Bull. Chem. Soc. Jpn. Vol. 84, No. 3 (2011)
PhF Synthesis from 1,1-Difluorocyclohexane
f) P. Tang, T. Furuya, T. Ritter, J. Am. Chem. Soc. 2010, 132,
12150.
13 D. A. Watson, M. Su, G. Teverovskiy, Y. Zhang, J. Garcia-
Fortanet, T. Kinzel, S. L. Buchwald, Science 2009, 325, 1661.
14 S. Yamada, A. Gavryushin, P. Knochel, Angew. Chem., Int.
Ed. 2010, 49, 2215.
15 P. Anbarasan, H. Neumann, M. Beller, Angew. Chem., Int.
Ed. 2010, 49, 2219.
16 M. Tojo, S. Fukuoka, Jpn. Kokai Tokkyo Koho JP 63-
088145, 1988; M. Tojo, S. Fukuoka, Chem. Abstr. 1988, 109,
189977.
that the calculated (ln[1] ¹ ln[1]0) of eq 1a had a linear relation-
ship with time. The rate constant k1 was calculated from the slope
of the linear plot to be 12.1 h¹1. The first-order rate constant k2 was
determined to be 3.3 h¹1 by trial-and-error-method using eq 3a {A
rough value of k2 was obtained as an initial value for the trial-and-
error method in the following manner. As shown in Figure 1, the
concentration of 3 has a maximum, where d[3]/dt = k1[1]m ¹
k2[3]m = 0. [1]m and [3]m are the concentrations of 1 and 3 when 3
¹1
is maximum. The value of k2 was calculated roughly to be 2.5 h
according to the relationship k2 = k1[1]m/[3]m = 12.1 © 0.13/
0.635 = 2.5 (h¹1) when t = 0.16 (h).}.
17 a) K. Uneyama, Organofluorine Chemistry, Blackwell,
Oxford, 2006, pp. 263-266. b) P. Kirsch, Modern Fluoroorganic
Chemistry: Synthesis, Reactivity, Applications, Wiley-VCH, Wein-
heim, 2004. c) R. D. Chambers, Fluorine in Organic Chemistry,
Blackwell, Oxford, 2004. d) Advances in Organic Synthesis,
Bentham Science, Sharjah, 2006, Vol. 2, pp. 3-592. e) T. Itoh, N.
Ishida, K. Mitsukura, K. Uneyama, J. Fluorine Chem. 2001, 112,
63. f) Y. Guo, K. Fujiwara, H. Amii, K. Uneyama, J. Org. Chem.
2007, 72, 8523. g) M. Tojo, S. Fukuoka, H. Tsukube, J. Fluorine
Chem. 2010, 131, 29.
18 a) M. Tojo, S. Fukuoka, Jpn. Kokai Tokkyo Koho JP 63-
041443, 1988; M. Tojo, S. Fukuoka, Chem. Abstr. 1988, 109,
230380. b) M. Tojo, S. Fukuoka, Jpn. Kokai Tokkyo Koho JP 63-
044536, 1988; M. Tojo, S. Fukuoka, Chem. Abstr. 1988, 109,
230381. c) M. Tojo, S. Fukuoka, Jpn. Kokai Tokkyo Koho JP 63-
054331, 1988; M. Tojo, S. Fukuoka, Chem. Abstr. 1989, 110,
74914. d) S. Fukuoka, M. Tojo, Jpn. Kokai Tokkyo Koho JP 1-
199922, 1989; S. Fukuoka, M. Tojo, Chem. Abstr. 1990, 112,
97726.
20 M. Hudlicky, J. Fluorine Chem. 1986, 32, 441.
21 a) D. R. Strobach, G. A. Boswell, Jr., J. Org. Chem. 1971,
36, 818. b) M. Tojo, S. Fukuoka, Jpn. Kokai Tokkyo Koho JP 63-
048235, 1988; M. Tojo, S. Fukuoka, Chem. Abstr. 1988, 109,
169917.
22 a) S. Fukuoka, M. Tojo, Jpn. Kokai Tokkyo Koho JP 62-
061930, 1987; S. Fukuoka, M. Tojo, Chem. Abstr. 1987, 107,
175646. b) M. Tojo, S. Fukuoka, Jpn. Kokai Tokkyo Koho JP 62-
019541, 1988; M. Tojo, S. Fukuoka, Chem. Abstr. 1987, 107,
39355. c) M. Tojo, S. Fukuoka, Jpn. Kokai Tokkyo Koho JP 62-
019540, 1987; M. Tojo, S. Fukuoka, Chem. Abstr. 1987, 107,
39354.
23 G. C. Bond, Metal-Catalysed Reactions of Hydrocarbons,
Springer, New York, 2005, pp. 509-514.
24 a) K. Uneyama, Organofluorine Chemistry, Blackwell,
Oxford, 2006, pp. 1-2. b) P. Atkins, Physical Chemistry, 5th ed.,
Freeman, New York, 1994, p. 488.
25 a) W. R. Hasek, W. C. Smith, V. A. Engelhardt, J. Am.
Chem. Soc. 1960, 82, 543. b) D. R. Strobach, G. A. Boswell, Jr.,
J. Org. Chem. 1971, 36, 818. c) C. Hu, F. Qing, C. Shen, J. Chem.
Soc., Perkin Trans. 1 1993, 335.
26 T. Ando, T. Ishihara, E. Ohtani, H. Sawada, J. Org. Chem.
1981, 46, 4446.
27 G. Wittig, U. Mayer, Chem. Ber. 1963, 96, 329.
28 MOPAC 2002, Version 2.0 for Windows, Fujitsu Ltd., 2008.
29 CS ChemBio3D Ultra, Version 11.0, CambridgeSoft, 2008.
19 The integral representations of the reaction rates are
ln½1ꢀ ꢁ ln½1ꢀ0 ¼ k1t
½3ꢀ ¼ ½1ꢀ0½k1=ðk2 ꢁ k1Þꢀ½expðꢁk1tÞ ꢁ expðꢁk2tÞꢀ
(1a)
(2a)
½2ꢀ ¼ ½1ꢀ0½1 þ 1=ðk1 ꢁ k2Þꢀ½k2 expðꢁk1tÞ ꢁ k1 expðꢁk2tÞꢀ (3a)
where [1]0 is the initial concentration of 1. First-order plot showed