Nucleophilic aryloxydefluorination of pentafluorobenzene without noble metal catalysis

Article abstract of DOI:10.1016/j.jfluchem.2013.05.016

1-Phenoxy-2,3,5,6-tetrafluorobenzene and 1-(40-fluorophenoxy)-2,3,5,6- tetrafluorobenzene were prepared in a quantitative yield from C ₆F₅H, ArOH and K₂CO₃ (DMF or DMSO, 120 8C, 9-11 h). The catalytic effect of Pd(OAc)₂ in the presence of AgNO₃ as claimed in Ref. [1] was not confirmed.

Full text of DOI:10.1016/j.jfluchem.2013.05.016

Journal of Fluorine Chemistry 153 (2013) 165–167
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Journal of Fluorine Chemistry
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Short communication
Nucleophilic aryloxydefluorination of pentafluorobenzene without
noble metal catalysis
b
Nicolay Yu. Adonin a, , Vadim V. Bardin
*
a G.K. Boreskov Institute of Catalysis, SB RAS, Acad. Lavrentjev Ave. 5, 630090 Novosibirsk, Russian Federation
b N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, SB RAS, Acad. Lavrentjev Ave. 9, 630090 Novosibirsk, Russian Federation
A R T I C L E I N F O
A B S T R A C T
1-Phenoxy-2,3,5,6-tetrafluorobenzene and 1-(40-fluorophenoxy)-2,3,5,6-tetrafluorobenzene were pre-
pared in a quantitative yield from C6F5H, ArOH and K2CO3 (DMF or DMSO, 120 8C, 9–11 h). The catalytic
effect of Pd(OAc)2 in the presence of AgNO3 as claimed in Ref. [1] was not confirmed.
ß 2013 Elsevier B.V. All rights reserved.
Article history:
Received 8 April 2013
Received in revised form 14 May 2013
Accepted 15 May 2013
Available online 31 May 2013
Keywords:
Pentafluorobenzene
Phenol
Nucleophilic substitution
NMR spectroscopy
1. Introduction
require a longer reaction time and gave low to medium product
yields. We were surprised with such a way to improve the well-
Substitution of nucleophilic reagents of different nature for
fluorine atom(s) in polyfluoroaromatic compounds is a well-
known reaction under intensive studies during the last five
decades. Numerous fundamental monographs and comprehensive
reviews [2] present synthetic results, as well as kinetic data and
theoretical considerations. Typical example is the substitution of
fluorine atom in pentafluorobenzene derivatives, C6F5X, by O-
nucleophiles MOR (R=H or organyl group). This reaction produces
ROC6F4X (primary product) provided that X is not a highly reactive
functional group or peculiar organoelement substituent.
We were interested in some aryloxytetrafluorobenzenes, 1-
ArO-2,3,5,6-C6F4H. Fortunately, synthesis of such diaryl ethers was
reported recently by Sandford et al. [3], and the protocols, after
slight modification, were successfully applied by us for preparation
of the required products. After accomplishing the work, we have
found another paper where a ligand-free palladium-catalyzed
method was offered for cross coupling reaction of C6F5H with
phenols [1]. The authors assert that the use Pd(OAc)2 as the
catalyst, AgNO3 as the additive and K2CO3 as the base leads to
polyfluorinated diaryl ethers in a moderate to excellent yield. The
known methods are, seemingly, less convenient because they
elaborated procedures and checked some aspects of the work [1].
2. Results and discussion
We discovered that the table of optimization (Table 1 [1])
presented data on the reaction of C6F5H with phenol and base in
the presence of either Pd(OAc)2 or AgNO3 (entries 1 and 2) but not
on any blind experiments, e.g. reaction without both Pd(OAc)2 and
an additive. We found that heating of C6F5H with PhOH (2
equivalents) and K2CO3 in DMF at 120 8C over a period of 10 h gives
1-phenoxy-2,3,5,6-tetrafluorobenzene (1) and 1,3-diphenoxy-
2,5,6-trifluorobenzene (2) in 90% and 8% yield, respectively (based
on pentafluorobenzene) (Scheme 1). The reported Pd-catalyzed
(Table 1, entry 3 [1]) reaction leads to 1 at the 93% yield (19F NMR).
In our experiments, this process results in a mixture of C6F5H (59%
conversion) and 1 (51% yield based on reacted pentafluoroben-
zene) (Scheme 2).
The further studies showed a similar picture. Ethers 1, 2 and,
probably, 1,2-(PhO)2-3,4,6-C6F3H are obtained at 69%, 22% and 3%
yield from C6F5H with PhOH and K2CO3 in DMSO without Pd(OAc)2
and AgNO3 (this work) while the Pd-catalyzed reaction (Table 1,
entry 15 [1]) gives 1-PhO-2,3,5,6-C6F4H in 75% yield.
Meanwhile, the formation of 2 can be easily prevented using
excess pentafluorobenzene. For example, stirring of C6F5H (excess)
with phenol and K2CO3 in DMF, followed by removal of
* Corresponding author. Tel.: +7 383 326 9674; fax: +7 383 330 8056.
E-mail address: adonin@catalysis.ru (N.Yu. Adonin).
0022-1139/$ – see front matter ß 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2013.05.016

166
N.Y. Adonin, V.V. Bardin / Journal of Fluorine Chemistry 153 (2013) 165–167
F
F
F
F
3. Conclusion
F
F
F
F
K2CO3 (2 equ.)
+ PhOH
F
The catalytic effect of Pd(OAc)2 on formation of 1-ArO-2,3,5,6-
C6F4H from C6F5H, ArOH (Ar55C6H5, 40-FC6H4) and K2CO3 (DMF or
DMSO, 120 8C, 12 h) [1] in the presence of AgNO3 was not
confirmed.
DMF, 120 °C, 10 h
PhO
F PhO
OPh
F
F
2 equ.
1 (90 %)
2 (8 %)
Scheme 1.
4. Experimental
F
F
Pd(OAc)2 (10 mol. %)
AgNO3 (1 equ.)
4.1. General
F
F
F
K2CO3 (2 equ.)
NMR spectra were acquired using a Bruker AVANCE 300
spectrometer (19F at 282.40 MHz). Chemical shifts are assigned to
CCl3F (19F, with C6F6 as secondary reference (ꢀ162.9 ppm)). A
Hewlett-Packard 1800A (with HP-5MS column) and Shimadzu
GCMS-QP 2010 Ultra instruments were used for GC–MS analysis.
The elemental analysis was performed in the Collective Service
Center of SB RAS (Novosibirsk).
+ PhOH
F
DMF, 120 °C, 12 h
PhO
F
F
F
1 equ.
2 equ.
93 % [1]
51 % [this work]
Scheme 2.
Dimethylformamide was distilled over P4O10 at reduced
pressure. Dimethyl sulfoxide (Panreac) was stirred with CaH2 and
distilled. Phenols were distilled in argon atmosphere. K2CO3 was
calcinated at 450 8C for 4 h before being use. Pentafluorobenzene
(Octa), Pd(OAc)2 (Acros) and AgNO3 (ABCR) were used as supplied.
Compounds 1 and 3 were completely characterized in Refs.
[1,3] by 1H, 13C, 19F NMR, IR, HRMS, mp., therefore they were
identified using only 19F NMR spectra, which are the most
informative for this aim (references on corresponding reported
spectra of 1 and 3 are given in Section 4), and GC–MS. Compound 2
(minor admixture) was identified in a mixture with 1 by 19F NMR
and GC–MS, which unambiguously show constitution of 2 as 1,3-
(PhO)2-2,5,6-C6F3H. Because of the low ratio 1:2 = 10:1, measure-
ment of 1H, 13C NMR spectra was not possible.
non-reacted C6F5H (bp 85–87 8C) from reaction mixture by
distillation and routine work up of the residue results in ether 1
(quantitative isolated yield) (Scheme 3). Again, 1-(40-fluorophe-
noxy)-2,3,5,6-tetrafluorobenzene (3) is prepared similar way at an
excellent yield (96% from 19F NMR spectrum and 88% of isolated
substance) (Scheme 4). For comparison, the Pd-catalyzed reaction
produced ether 3 at no more than 57% yield ([1], Table 2, entry 16)
(Scheme 5).
Thus, the reaction of pentafluorobenzene with phenols and a
base leads to the expected polyfluorinated diaryl ethers at an
excellent yield, i.e. there is the ordinary substitution of O-
nucleophile for aromatically bonded fluorine atom. Introduction
of Pd(OAc)2 and AgNO3 has no catalytic effect in synthesis of 1 in
DMF (Schemes 1 and 2) and has negative effect in synthesis 1
in DMSO and 3 in DMF (Schemes 4 and 5).
4.2. Reaction of C6F5H with phenols and K2CO3
A glass ampoule was flushed with dry argon and charged with
K2CO3 (153 mg, 1.10 mmol) and solution of C6F5H (88 mg,
0.52 mmol) and PhOH (101 mg, 1.07 mmol) in DMF (3 mL). After
sealing by flame, it was kept at 120 8C for 10 h and cooled to 25 8C.
A probe of the mother liquor contained 1-PhO-2,3,5,6-C6F4H [3]
(0.47 mmol), 1,3-(PhO)2-2,5,6-C6F3H (0.04 mmol) and probably,
1,2-(PhO)2-2,5,6-C6F3H (trace) (19F NMR, C6F6 quantitative internal
reference). GC–MS analysis showed PhOH (21%), 1-PhO-2,3,5,6-
C6F4H (66%) and isomers (PhO)2-2,5,6-C6F3H (1 + 11%).
F
F
F
F
F
K2CO3 (2 equ.)
+ PhOH
F
DMF, 120 °C, 11 h
PhO
F
F
F
excess
1 equ.
1 (100 %)
1,3-(PhO)2-2,5,6-C6F3H (2) (mixture with 1). 19F NMR (DMF):
d
ꢀ139.4 (ddd, 3J(F5, F6) = 22 Hz, 3J(F5, H4) = 9 Hz, 5J(F5, F2) = 11 Hz,
1F, F5), ꢀ148.0 (dd, 5J(F2, F5) = 11 Hz, 4J(F2, H6) = 8 Hz, 1F, F2), ꢀ155.5
(dd, 3J(F6, F5) = 22 Hz, 4J(F6, H4) = 8 Hz, 1F, F6). GC–MS: M+ 316.
Reaction in DMSO was performed similar way to give 1-PhO-
2,3,5,6-C6F4H, 1,3-(PhO)2-2,5,6-C6F3H and, probably, 1,2-(PhO)2-
2,5,6-C6F3H in 69%, 22% and 3% yield (19F NMR, C6F6 as the
quantitative internal reference).
A glass ampoule equipped with a stir bar was flushed with dry
argon and charged with K2CO3 (960 mg, 6.9 mmol) and solution of
C6F5H (2.8 g, 16.6 mmol) and PhOH (620 mg, 6.5 mmol) in DMF
(6 mL). The ampoule was sealed by flame and the suspension was
stirred at 120 8C for 11 h. After cooling to 25 8C, pentafluoroben-
zene (1.5 g) was distilled off from reaction mixture. Residue was
poured out into water (80 mL), extracted with CH2Cl2
(3 mL ꢁ 10 mL), the extract was dried with MgSO4 and the solvent
was removed under reduced pressure to give 1-PhO-2,3,5,6-C6F4H
(1.55 g, 99%).
Scheme 3.
F
F
F
F
F
F
F
F
O
K2CO3 (2 equ.)
+
DMF, 120 °C, 9 h
F HO
F
F
excess
1 equ.
3 (96 %)
Scheme 4.
F
F
Pd(OAc)2 (10 mol. %)
AgNO3 (1 equ.)
K2CO3 (2 equ.)
F
F
F
F
+
DMF, 120 °C, 12 h
F
F HO
O
F
A glass ampoule equipped with a stir bar was flushed with dry
argon and charged with K2CO3 (435 mg, 3.1 mmol) and solution of
C6F5H (1.44 g, 8.5 mmol) and 4-fluorophenol (345 mg, 3.8 mmol)
in DMF (5 mL). The ampoule was sealed by flame and the
F
F
1 equ.
2 equ.
3 (57 %) [1]
Scheme 5.

N.Y. Adonin, V.V. Bardin / Journal of Fluorine Chemistry 153 (2013) 165–167
167
suspension was stirred at 120 8C for 9 h. Unreacted pentafluor-
obenzene (882 mg, 5.25 mmol) was distilled off from the reaction
mixture. The residue was poured out into water (75 mL) acidified
with 5% HCl, extracted with CH2Cl2 (2 mL ꢁ 25 mL), the extract
was dried with MgSO4 and concentrated under reduced pressure to
(24 mg, 0.10 mmol), AgNO3 (368 mg, 2.16 mmol) and a solution of
C6F5H (184 mg, 1.09 mmol) and PhOH (191 mg, 2.03 mmol) in
DMF (4 mL). The ampoule was sealed by flame and the suspension
was stirred at 120 8C for 12 h. After cooling to 25 8C, the reaction
mixture was filtered. A probe of the filtrate showed resonances of
C6F5H (0.45 mmol) and 1-PhO-2,3,5,6-C6F4H (0.33 mmol) besides
minor unknown products.
give
crude
1-(40-fluorophenoxy)-2,3,5,6-tetrafluorobenzene
(2.88 mmol, 96%) (19F NMR, internal quantitative reference PhCF3).
Pure ether 3 was obtained by steam-distillation (686 mg, 88%).
1-(40-FC6H4O)-2,3,5,6-C6F4H (3). 19F NMR (DMF):
d
ꢀ119.4 (tt,
3
4
3 ,5
4
4
2 ,6
4
0
0
0
0
0
J(F , H 0) = 7 Hz, J(F , H 0) = 5 Hz, 1F, F ), ꢀ138.8 (ddd,
References
3J(F3, F2) = 21 Hz, 3J(F3, H4) = 9 Hz, 5J(F3, F6) = 9 Hz, 2F, F3,5),
ꢀ154.8 (ddd, 3J(F2, F3) = 21 Hz, 4J(F2, H4) = 8 Hz, 5J(F2, F5) = 9 Hz,
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2F, F2,6) (cf. 19F NMR (CDCl3):
ꢀ138.47 to ꢀ138.63 (m, 2F), ꢀ154.19 to ꢀ154.32 (m, 2F) [1]).
d
ꢀ119.53 to ꢀ119.72 (m, 1F),
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(b) G.G. Yakobson, V.M. Vlasov, Synthesis (1976) 652–672;
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4.3. Reaction of C6F5H with phenol in the presence of Pd(OAc)2 and
AgNO3
A glass ampoule equipped with a stir bar was flushed with dry
argon and charged with K2CO3 (248 mg, 1.8 mmol), Pd(OAc)2