Regioselective ortho-hydrodefluorination of pentafluorobenzoic acid by low-valent nickel complexes

Article abstract of DOI:10.1016/S0022-1139(99)00181-5

2,3,4,5-Tetrafluorobenzoic and 3,4,5-trifluorobenzoic acids were prepared in high yields by reaction of C₆F₅COOH with zinc in the presence of NiCl₂-2′-bipyridine (or 1,10-phenanthroline) complexes.

Full text of DOI:10.1016/S0022-1139(99)00181-5

Journal of Fluorine Chemistry 101 (2000) 65±67
Regioselective ortho-hydrode¯uorination of penta¯uorobenzoic
acid by low-valent nickel complexes
N.Yu. Adonin, V.F. Starichenko*
N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, 630090 Novosibirsk, Russia
Received 14 June 1999; accepted 3 August 1999
Abstract
2,3,4,5-Tetra¯uorobenzoic and 3,4,5-tri¯uorobenzoic acids were prepared in high yields by reaction of C6F5COOH with zinc in the
presence of NiCl2±20-bipyridine (or 1,10-phenanthroline) complexes. # 2000 Elsevier Science S.A. All rights reserved.
Keywords: Hydrode¯uorination; Nickel complexes; Reductive de¯uorination
1. Introduction
entries 1,2). However, in the presence of in situ genera-
ted catalysts NiCl2±Bipy (or phen) (1 mol%), 2,3,4,5-
tetra¯uorobenzoic acid was obtained in 83% yield (Table
1, entry 3).
There are several methods of hydrode¯uorination of
penta¯uorobenzoic acid 1. Electrochemical reduction leads
to the formation of 2,3,5,6-tetra¯uorobenzoic acid 2 together
with ¯uorine containing benzaldehydes and benzyl alcohols
[1]. Action of sodium in liquid ammonia on acid 1 results in
a complex mixture of ¯uorobenzoic acids C6HnF5 nCOOH
(n ˆ 0±5) [2]. Reduction of 1 with zinc [2] or Zn(Cu) couple
[3,4] proceeds more selectively and gives only acid 2.
In contrast, the interaction of acid 1 with ytterbium(II)
compounds yields mainly 2,3,4,5-tetra¯uorobenzoic acid 3.
Indeed, a mixture of both acids 2 and 3 are obtained from
C6F5COOH and ytterbium(II) iodide [5]. Regiospeci®c
ortho-hydrode¯uorination of 1 takes place under the action
of bis(penta¯uorophenyl)ytterbium or Yb(Cp2)dme [6,7].
Recently we showed that hexa- and penta¯uorobenzenes,
octa¯uoronaphthalene and penta¯uoropyridine react easily
with zinc dust in the presence of NiCl2±2,20-bipyridine
(Bipy) (or 1,10-phenanthroline (Phen)) to give the less
¯uorinated benzenes, naphthalenes and pyridines [8]. In
the course of our systematic investigation, we studied the
reactions of C6F5COX (X ˆ OH, OC2H5, NH2) with the
above mentioned reductive system.
Increased amount of catalyst (up to 5 mol%) and the
reaction duration favoured the further removal of ortho-
¯uorine atoms (Table 1, entry 4). In this way, acid 4 was
obtained in quantitative yield.
To study the reaction conditions, we investigated some
factors which in¯uenced the reaction routes. For instance,
interaction of 1 with a reduced amount of zinc (2.3 eqv.) and
NiCl2±Bipy (1 mol%) resulted in ca. 10% conversion of the
substrate within 2 h (Table 1, entry 5). Increasing the amount
of catalyst to 5 mol% and the reaction duration to 4 h did not
affect on the conversion of acid 1 (Table 1, entry 6).
2. Results and discussion
Penta¯uorobenzoic acid did not react with zinc dust or
Zn±NiCl2 (5 mol%) in aqueous DMF at 708C (Table 1,
*Corresponding author. Fax: ‡7-3832-34-47-52.
E-mail address: vstar@nioch.nsc.ru (V.F. Starichenko)
0022-1139/00/$ ± see front matter # 2000 Elsevier Science S.A. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 9 9 ) 0 0 1 8 1 - 5

66
N.Y. Adonin, V.F. Starichenko / Journal of Fluorine Chemistry 101 (2000) 65±67
Table 1
Reaction of C6F5COOHa with NiCl2±Bipy (or Phen)±Zn in DMF
Entry Catalyst
Composition
Proton
source
Molecular ratio Temperature Time (h) Conversion Yield
‡
Product distribution
(mol%)
(1 : Zn : H )
(8C)
of 1 (%)
(g)
Amount
(mol%)
3
4
1
±
0
5
1
5
1
5
5
5
5
5
5
5
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
NH4Cl
NH4Cl
±
1 : 10 : 56
1 : 10 : 56
1 : 10 : 56
1 : 10 : 56
1 : 2.3 : 56
1 : 2.3 : 56
1 : 2.3 : 56
1 : 3 : 56
1 : 3 : 2
70
70
60
60
70
70
50
50
50
50
70
35
24
24
ꢁ0
ꢁ2
83
2.1
2.0
±
±
±
±
±
2
NiCl2
3
NiCl2±Bipy
NiCl2±Bipy
NiCl2±Phen
NiCl2±Phen
NiCl2±Phen
NiCl2±Phen
NiCl2±Phen
NiCl2±Bipy
NiCl2±Bipy
NiCl2±Bipy
0.75
1.8
100
±
4
6
100
9.5
9.7
63
1.5
100
±
5
1
1.7
100
100
95
77
5
6
4
1.5
±
7
4
1.68
1.7
5
8
6
83
23
95
100
4
9
1
100
100
64
1.8
10
11
12
1 : 3 : 2
1
1.72
1.73
1.8
±
1 : 5 : 0
1.5
6
96
87
NH4Cl
1 : 3 : 2
96
13
a The amount of 1 2.12 g (10 mmol).
Surprisingly, lowering the temperature to 508C increased
the conversion of 1 to 63% under the same reaction con-
ditions (Table 1, entry 7). The probable reason is in deac-
tivation of the catalyst at high temperatures. The conversion
of 1 increased to 83% when 3 equ. of zinc were used, but
simultaneously the ratio 3 to 4 changed from 95 : 5±77 : 23
(Table 1, entry 8).
The replacement of water by ammonium chloride as
proton donor led to acceleration of hydrode¯uorination.
Thus, reaction of acid 1 with NiCl2±Bipy (or Phen)±Zn±
NH4Cl in DMF gave 3,4,5-tri¯uorobenzoic acid 4 in nearly
quantitative yield at 508C within 1 h (Table 1, entries 9, 10).
At the lower temperature (358C) we obtained the opposite
result: acid 3 became the main product (Table 1, entry 11). A
similar picture was observed at 708C without ammonium
chloride (Table 1, entry 12). In this case the starting acid or
NiCl2Á6H2O could be the proton sources.
Under similar conditions, the reactivity of C6F5COX
increased in the order X ˆ NH2 < OH < OC2H5. Moreover,
no derivatives of benzoic acid 4 were found when the
conversions 5 or 6 did not exceed ca. 60%.
We assume that above mentioned transformations involve
the generation of zero-valent nickel complexes and follow
formation of a hydride complex 7, which acted as the
reactive intermediate.
It should be noted that the catalytic activity of NiCl2±
Bipy does not differ from that of NiCl2±Phen.
In contrast to acid 1, the reactions of ethyl penta¯uor-
obenzoate 5 or penta¯uorobenzamide 6 with NiCl2±Bipy
(or Phen)±Zn proceed with less regioselectivity to give
comparable amounts of 2,3,4,5- and 2,3,5,6-C6HF4COX
(X ˆ OC2H5, NH2) (Table 2).
NiCl2 ‡ nL ‡ Zn ˆ ZnCl2 ‡ Niꢀ0†Ln
n ˆ 1; 2; L ˆ 2; 20-bipyridine; 1; 10-phenanthroline
Niꢀ0†Ln ‡ HX ˆ HNiꢀII†XLn
7
The reaction pathway of the intermediate 7 is determined
by the structure of the poly¯uoroarene. The normal nucleo-
philic ortho- and para-hydrode¯uorination takes place when
poly¯uoroarenes were C6F6, C6F5H, C5F5N, C10F8 [8] as
well as ester 5 and amide 6. Alternatively, the regioselective
ortho-hydrode¯uorination of acid 1 can be rationalized as an
intramolecular process via the coordination of the car-
boxylic group with intermediate 7 (cf. [7]). The latter
pathway seems to partially contribute also to ortho-hydro-
de¯uorination of 5 and 6, increasing the yield of the
corresponding 2,3,4,5-C6F4HCOX derivatives (cf. hydrode-
¯uorination with LiAlH4 [9]).
Table 2
Interaction of ethyl pentafluorobenzoate 5 and pentafluorobenzamide 6
with NiCl2±Bipy±Zn
Entry
Substrate
Time
(h)
Conversion
(%)
Isomer distribution
(mol%)
a
b
1
2
3
5
6
6
2
2
4
47
22
59
43
73
64
57
27
36

N.Y. Adonin, V.F. Starichenko / Journal of Fluorine Chemistry 101 (2000) 65±67
67
3. Experimental
with MgSO4 and ether was removed under reduced
pressure. A solid residue was crystallised from hexane.
Yields and composition of products are in Table 1.
2. Reactions of ester 5 or amide 6 (10 mmol) with
NiCl2Á6H2O (120 mg, 0.5 mmol), Bipy (80 mg,
0.5 mmol) and zinc dust (1.3 g, 20 mmol) were
performed in a similar way (see Table 2).
19F NMR spectra were measured on a Bruker WP-200SY
instrument at 188.3 MHz with respect to internal C6F6.
HPLC analysis was carried out on a Milichrom-4 chroma-
tograph equipped with a UV detector (at 230 and 254 nm).
A Separon C-18 analytical column (2 mm i.d. Â 6.2 cm) at
408C was used with 40% methanol in 0.1% aqueous phos-
phoric acid and the ¯ow rate was 200 ml/min.
The reaction products 3, 4, 5a, 5b, 6a and 6b were
identi®ed by 19F NMR spectrometry.
3.1. Hydrodefluorination of pentafluorobenzoic acid and
its derivatives (general procedure)
References
1. A three-necked flask (25 ml) equipped with the
thermometer and magnetic stirrer was charged with
NiCl2Á6H2O, Bipy (or Phen), zinc dust, DMF (10 ml)
and H2O (or NH4Cl). The stirred reaction mixture was
warmed and kept for within 30 min. Then a solution of
acid 1 in DMF (5 ml) was added and the resulting
suspension was kept under HPLC control. Then it was
filtered, the solid residue was washed with DMF and
washings were combined with the filtrate. The latter
was diluted with water and extracted with diethyl ether
(5 Â 10 ml). The extract was washed with water, dried
[1] F.G. Drakesmith, J. Chem. Soc., Perkin Trans. 1 (1972) 184.
[2] S.S. Laev, V.D. Shteingarbs, Tetrahedron Lett. 38 (1997) 3765.
[3] V.I. Krasnov, V.E. Platonov, Zh. Org. Khim. 29 (1993) 1078.
[4] V.E. Platonov, V.I. Krasnov, Zh. Org. Khim. 30 (1994) 1271.
[5] G.B. Deacon, P.I. MacKinnon, T.D. Tuong, Aust. J. Chem. 36 (1983)
43.
[6] G.B. Deacon, P.I. MacKinnon, Tetrahedron Lett. 25 (1984) 783.
[7] G.B. Deacon, C.M. Forsyth, J. Sun, Tetrahedron Lett. 35 (1994)
1095.
[8] N.Yu. Adonin, V.F. Starichenko, Mendeleev Commun., in press.
[9] G.M. Brooke, J. Fluorine Chem. 86 (1997) 1.