Preparation of organozinc compounds from 3-chloroheptafluorotoluene and zinc: The participation of C-F bonds

Article abstract of DOI:10.1070/MC2006v016n03ABEH002266

Organozinc compounds were obtained from 3-chloroheptafluorotoluene and Zn in DMF; the C-Cl bond is mainly involved in this reaction; the addition of SnCl₂ changes the main reaction course in the direction of the participation of the C-F bond (p

Full text of DOI:10.1070/MC2006v016n03ABEH002266

Mendeleev
Communications
Mendeleev Commun., 2006, 16(3), 168–170
Preparation of organozinc compounds from 3-chloroheptafluorotoluene and zinc:
the participation of C–F bonds
Vyacheslav I. Krasnov, Andrey S. Vinogradov and Vyacheslav E. Platonov*
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences,
630090 Novosibirsk, Russian Federation. Fax: +7 383 330 9752; e-mail: platonov@nioch.nsc.ru
DOI: 10.1070/MC2006v016n03ABEH002266
Organozinc compounds were obtained from 3-chloroheptafluorotoluene and Zn in DMF; the C–Cl bond is mainly involved in this
reaction; the addition of SnCl2 changes the main reaction course in the direction of the participation of the C–F bond (para to the
CF3 group).
Perfluoroarenes react with zinc in dimethylformamide (DMF)
in the presence of metal salts (SnCl2, CuCl2 or ZnBr2) to give
perfluorozincarenes as the formal result of fluorine atom sub-
stitution with zinc in the aromatic ring.1 Chloropentafluoro-
benzene reacted with zinc at the C–Cl bond to give penta-
fluorophenylzinc chloride under similar conditions.1
tion of polyfluoroaromatic organozinc compounds at C–Cl
bonds took place, whereas C–F bonds were unaffected.2 Here,
the formation of organozinc compounds with the participation
of the C–F bond of the aromatic ring of a polychlorofluoroarene
under the action of Zn and SnCl2 is considered.
We studied the reaction of 3-chloroheptafluorotoluene 1 with
Zn in dry DMF in order to obtain organozinc compounds.†
It was found that the interaction of compound 1 with Zn(Cu) in
We found that polychlorofluoroarenes react with Zn in DMF
upon heating without addition of salts; in all cases, the forma-
168 Mendeleev Commun. 2006

Mendeleev Commun., 2006, 16(3), 168–170
between two competitive locations of metallation of arene 1;
H
F
3
ZnX
F
Cl
F
Cl
F
it follows from the ratio of reaction products, which were
obtained by the hydrolysis of a mixture of organozinc com-
pounds (ratios of 31:69 and 26:74 in favour of fluorine atom
substitution).
ZnX
i
ii
2 +
F3C
F3C
F3C
F3C
Proportion of fluorine atom substitution in compound 1 reduced
but kept a considerable value when tin powder was used instead
of SnCl2 for the formation of organozinc compounds (run 6,
Table 1). In this case, the consumption of compound 1 was reduced
in comparison with the use of Zn–SnCl2 or only Zn. Thus, the
addition of SnCl2 promotes the formation of organozinc com-
pounds with the participation of a C–F bond of toluene 1 (the
4-position); it is in agreement with the orientation, which was
observed in the nucleophilic substitution reaction of 1 with
dimethyl amine, where the dimethyl amine group enters mainly
at the 4-position to give N-[2-chloro-3,5,6-trifluoro-4-(trifluoro-
methyl)phenyl]-N,N-dimethylamine 8.¶¶ At the same time, no
reaction between SnCl2 or Sn/SnCl2 and 1 in a DMF solution
(70 °C) in the absence of Zn was found to detect the formation
of organostannane compounds or products of substitution of
fluorine atoms by chlorine in 1. In this connection, the assump-
tion of the initial nucleophilic substitution of fluorine atoms
with chlorine at the 4-position of arene 1 under the action of
2
1
4
a X = Cl
b X = 3-CF3C6F4
a X = Cl
b X = 3-CF3C6F4,
2-Cl-4-CF3C6F3
Scheme 1 Reagents and conditions: DMF, 70 °C; i, Zn; ii, Zn/SnCl2.
aqueous DMF took place with participation of the C–Cl bond
to give the product of hydrodechlorination.2
Compound 1 reacted with Zn in dry DMF to give pre-
dominantly organozinc compounds 2‡ (Scheme 1) as result
of the participation of the C–Cl bond in the reaction (run 1,
Table 1). Note that 3-H-heptafluorotoluene 3 as a product of
formal hydrolysis of 2 was also observed in the reaction.
Unexpectedly, the addition of ~10–11 mol% SnCl2 (relative to 1)
to zinc changed the reaction course (runs 2, 3; Table 1). In this
case, organozinc compounds 4§ were obtained as the major
products along with smaller amounts of 2 (Scheme 1).
These data are in agreement with the results of treatment of
a mixture of organozinc compounds 2 and 4 with hydrochloric
acid and bromine;¶ this treatment gave the hydrolysis products
3, 1-chloro-2,4,5-trifluoro-3-(trifluoromethyl)benzene 5†† and
bromo compounds [1-bromo-2,3,4,6-tetrafluoro-5-(trifluoro-
methyl)benzene 6‡‡ and 1-bromo-2-chloro-3,5,6-trifluoro-4-(tri-
fluoromethyl)benzene 7§§], respectively (Table 2, Scheme 2).
An increase of the relative quantity of SnCl2 to 100 or 300 mol%
(runs 4, 5; Tables 1, 2) insignificantly affects the correlation
H
F
Br
F
Cl
Br
Cl
H+
Br2
3
2
4
F
CF3
CF3
CF3
6
7
5
Scheme 2
†† Compound 5. Reaction mixture (run 4, Table 2) was fractionated
in vacuo. Fraction (79–79.5 °C/35 Torr) contained 96% compound 5.
†
General procedure. DMF was stored over KOH, fractionally distilled
4
4
under reduced pressure, and the main fraction was stored over CaH2.
Compound 1 (95%) contained ~4% 2-H-3-chlorohexafluorotoluene (GC/MS
and NMR). To a mixture of Zn dust (fivefold amount over stoichio-
metry) or Zn dust together with SnCl2 or another addition, DMF (0.4 ml
per 1 mmol of 1) compound 1 was added. The mixture was stirred by
a magnetic stirrer in a closed flask immersed in a thermostat. After
completion of the reaction and subsequent precipitation process, the
solution was decanted and the 19F NMR spectrum of the solution was
recorded (Table 1). The 19F and 1H NMR spectra were obtained on a
Bruker WP-200SY instrument at 188.3 and 200 MHz for reaction
mixtures containing organozinc compounds in DMF, as well as in other
cases for solutions in CCl4; the internal standards were C6F6 (162.9 ppm
from CCl3F) and HMS (0.04 ppm from TMS). The 19F chemical shifts
are reported vs. CCl3F.
19F NMR, d: –57.6 (quasitriplet, 3F, CF3, JCF –F(2) ~ 22.7 Hz, JCF –F(4)
3
3
4
5
~ 22.7 Hz), –116.6 (qddd, 1F, F-2, JCF –F(2) 22.4 Hz, J2,5 13.7 Hz,
3
4JF(2)–H 6.6 Hz, 4J2,4 ~ 2.5 Hz), –135.8 (qddd, 1F, F-4, 4JCF –F(4) 22.8 Hz,
3
4
4
3
3J4,5 20.5 Hz, JF(4)–H 7.8 Hz, J2,4 2.5 Hz), –138.5 (ddd, 1F, F-5, J4,5
5
3
1
20.4 Hz, J2,5 13.6 Hz, JF(5)–H 9.0 Hz). H NMR, d: 7.49 (quasiquartet,
broadened peaks, 23.2 Hz). IR (CCl4, n/cm–1): 3124, 3071, 1633, 1498,
1315, 1207, 1158, 922, 872, 834. HRMS for C7HClF6: found, 233.96741;
calc., 233.96709.
‡‡ Compound 6. Reaction mixture (run 3, Table 2) was fractionated
in vacuo. Fraction (69–69.5 °C/18 Torr) contained 98% compound 6.
4
4
19F NMR, d: –57.6 (quasitriplet, 3F, CF3, JCF –F(4) ~ 22.5 Hz, JCF –F(6)
3
3
4
5
~ 22.5 Hz), –108.8 (qddd, 1F, F-6, JCF –F(6) ~ 22.5 Hz, J3,6 ~ 9.5 Hz,
3
4J4,6 ~ 4 Hz, J2,6 ~ 1.5 Hz), –118.4 (dd, 1F, F-2, J2,3 21.7 Hz, J2,4
4
3
4
4
3
10.2 Hz), –133.8 (qddd, 1F, F-4, JCF –F(4) 22.7 Hz, J3,4 20.9 Hz,
3
[2,3,4,6-Tetrafluoro-5-(trifluoromethyl)phenyl]zinc chloride 2a. 19F NMR,
4J2,4 10.0 Hz, 4J45,6 3.7 Hz), –160.4 (quasitriplet d, 1F, F-3, 3J2,3 ~ 21.3 Hz,
3J3,4 ~ 21.3 Hz, J3,6 9.7 Hz). IR (CCl4, n/cm–1): 1638 (m), 1609, 1502,
1474, 1318, 1214, 1184, 1158, 1090, 918. HRMS for C7BrF7: found,
295.90721; calc., 295.90716. MS, m/z (%): 298 (M+, 96) 296 (M+, 100),
279 (M+ – F, 38), 277 (M+ – F, 41), 248 (M+ – CF2, 19), 246 (M+ – CF2,
19), 217 (M+ – Br, 51). Found (%): C, 28.11; Br, 26.86; F, 45.02. Calc. for
C7BrF7 (%): C, 28.31; Br, 26.91; F, 44.78.
‡
d: ~ –55.5 (quasitriplet, 3F, CF3, 4JCF –F(4) ~ 22 Hz, 4JCF –F(6) ~ 22 Hz), –89.5
(qdd, 1F, F-6, 4JCF –F(6) 21.3 Hz, 5J33,6 14.6 Hz, 4J4,6 3.9 Hz), –102.9 (dd,
3
3
1F, F-2, 3J2,3 31.2 Hz, 4J2,4 9.3 Hz), –138.3 (qddd, 1F, F-4, 4JCF –F(4) 23.5 Hz,
3J3,4 18.6 Hz, 4J2,4 9.2 Hz, 4J4,6 3.8 Hz), –165.6 (ddd, 1F, F-3, 33J2,3 31.3 Hz,
3J3,4 18.6 Hz, 5J3,6 14.6 Hz). Spectrum of the reaction mixture also contains
the signals of 2b (X = 3-CF3C6F4): –55.5, –89.9, –103.3, –139.2, –165.9.
Fine structure of the signals is similar to 2a excepting 3J2,3 32.3 Hz.
§§ Compound 7. Reaction mixture (run 3, Table 2) was fractionated
in vacuo to give a fraction (95–96.5 °C/17 Torr) containing 96% com-
§
[2-Chloro-3,5,6-trifluoro-4-(trifluoromethyl)phenyl]zinc chloride 4a.
4
4
4
19F NMR, d: –55.6 (quasitriplet, 3F, CF3, JCF –F(3) ~ 22 Hz, JCF –F(5)
pound 7 and 1% compound 6. 19F NMR, d: –57.9 (t, 3F, CF3, JCF –F(3)
~ 22 Hz), –114.9 (dd, 1F, F-6, 3J5,6 31.0 Hz, 5J3,6 18.5 Hz), –115.8 (3qdd,
22.4 Hz, JCF –F(5) 22.4 Hz), –112.4 (qdd, 1F, F-3, JCF –F(3) 22.4 Hz,
3
3
4
4
3
1F, F-3, 4JCF –F(3) 22.1 Hz, 5J3,6 18.5 Hz, 4J3,5 ~ 4.5 Hz), –138.5 (dqd, 1F,
5J3,6 11.7 Hz, 4J3,5 2.7 Hz), –126.9 (dd, 1F, F-6, 3J5,6 21.9 Hz,35J3,6 11.7 Hz),
3
3
4
4
4
3
F-5, J5,6 31.0 Hz, JCF –F(5) 22.4 Hz, J3,5 ~ 4 Hz). Spectrum of the
–135.0 (quasiquintet d, 1F, F-5, JCF –F(5) ~ 22.4 Hz, J5,6 ~ 22.4 Hz,
4J3,5 2.7 Hz). IR (CCl4, n/cm–1): 1625, 13593 (weak), 1471, 1313, 1159 (m),
1090, 949, 873. HRMS for C7ClBrF6: found, 311.87766; calc., 311.87761.
MS, m/z (%): 316 (M+, 24), 314 (M+, 100), 312 (M+, 75), 295 (M+ – F,
22), 293 (M+ – F, 18), 279 (M+ – Cl, 16), 277 (M+ – Cl, 18), 264 (M+ – CF2,
14), 262 (M+ – CF2, 11), 235 (M+ – Br, 9), 233 (M+ – Br, 27). Found
(%): C, 26.54; F, 36.17. Calc. for C7ClBrF6 (%): C, 26.82; F, 36.37.
¶¶ Reaction of compound 1 with HNMe2. 16.2 mmol HNMe2 (2.21 g of a
33% aqueous solution) was added to a solution of 1 in 12.6 ml of DMF
and shaken. After four days, the resulting mixture was diluted with 12 ml
of 5% aqueous HCl, the organic layer was separated and dried over
Na2SO4. Liquid (2.28 g) contained 80% compound 8 according to GLC
3
reaction mixture also contains the signals of 4b (X = 2-Cl-4-CF3C6F3):
–55.6, –115.5, –116.1, –139.2. Fine structure of the signals is similar to
4a excepting 3J5,6 ~ 32 Hz. For mixtures of 2 and 4, the signals of 2b and
4b (X = 3-CF3C6F4, 2-Cl-4-CF3C6F3) are close overlapping sets assigned
to the structures of Ar2Zn and ArAr'Zn types.
¶
Hydrogen derivatives were obtained by treatment of the solution and
solid material after decantation of the solution with dilute HCl. Bromo
derivatives were synthesised in the following manner: to a mixture of
bromine (an equimolar amount vs. compound 1) in DMF the decanted
solution was added. The solid material was washed with a small amount
of DMF (3–5 ml) and the solution was added to the above mixture.
Reaction mixtures were steam distilled; if necessary, the organic layer
was separated and treated with a 10% aqueous solution of Na2SO3 until
the disappearance of its colour to remove the excess of bromine. Then,
the organic layer was dried over CaCl2.
and GC-MS. 19F NMR, d: –57.2 (quasitriplet, 3F, CF3, 4JCF –F(3) ~ 21.8 Hz,
3
4JCF –F(5) ~ 21.8 Hz), –116.3 (qdd, 1F, F-3, 4JCF –F(3) 21.6 Hz, 5J3,6 9.5 Hz,
3
4J3,5 2.3 Hz), –138.4 (qdd, 1F, F-5, 4JCF –F(5) ~322 Hz, 3J5,6 18.9 Hz, 4J3,5
3
2.3 Hz), –150.9 (m, 1F, F-6, 35 Hz breadth and 16 peaks at least).
Mendeleev Commun. 2006 169

Mendeleev Commun., 2006, 16(3), 168–170
Table 1 Reaction of 3-chloroheptafluorotoluene 1 with Zn (70 °C, 8 h).
Concentrations (ratio) of products
in the reaction mixturea,b
Addition
g (mmol)
Compound 1/
g (mmol)
Ratio
Run
4:2b
mol%
1
2 (a:b)
3
4 (a:b)
5
c
1
4.04 (16.0)
3.20 (12.7)
6.65 (26.3)
4.04 (16.0)
4.04 (16.0)
4.04 (16.0)
—
—
4.4
0.5
0
0
—
92.0 (7:3)
36.0 (5.5:4.5)
32.9 (5.5:4.5)
36.9 (6.5:3.5)
—
3.5
1.4
0.4
0.7
—
—
0
~0c
2
3d
4
5
6
SnCl2, 10
SnCl2, 11
SnCl2, 100
SnCl2, 300
Sn, 10
0.24 (1.3)
0.57 (3.0)
3.00 (15.8)
9.10f (48.0)
0.19 (1.6)
59.0 (~5.5:4.5)
61.8 (5.5:4.5)
57.8 (~6.5:3.5)
—
3.1
4.9
4.6
—
0.7
62:38
65:35
61:39e
g
—
41.6
30.1 (6:4)
2.3
25.3 (6:4)
46:54
aRatios of 2a and 2b, 4a and 4b are given by polyfluoroaromatic fragments considering organozinc compounds as molecules with such a fragment. bValues
were found by 19F NMR spectroscopy. cPrecise estimate failed because of a very small quantity of 4. d27 h. eAfter the reaction, a decanted solution contained
only partly organometallic compounds; the significant portion of the reaction mixture was likely in a solid phase untested by 19F NMR. f12.1 ml of DMF
(0.8 ml per 1 mmol of 1) was also used in the reaction. gReaction mixture is thick mass; compound 1 was mainly detected in solution by 19F NMR
spectroscopy.
Table 2 Treatment of reaction mixtures of organozinc compounds 2 and 4 by Br2 and HCl.a
Concentrations (yield) of reaction product mixture according to GLC (%)
Yield of product
Run
Reagent/g (mmol)
Ratio 7:6b
mixture/g
1
3
5
6
7
1
Br2, 2.6 (16.3)
Br2, 2.1 (13.1)
Br2, 3.7 (23.2)
HCld
3.80
2.23
5.75
2.97
2.90
3.88
5.1 (4.8)
—
—
2.6 (2.8)
1.4 (1.2)
5.6 (6.6)
26.1 (22.2)
19.6 (16.3)
1.5 (1.7)
—
84.1 (67.3)
33.7 (20.0)
28.3 (24.5)
—
0.7 (0.5)
55.8 (31.3)
43.4 (35.6)
—
<1:100
61:39
59:41
69:31e
74:26e
44:56
2
3c
4
5
6
3.2 (2.4)
15.4 (16.9)
63.7 (50.4)
59.6 (46.1)
1.6 (1.7)
—
HCld
14.9 (10.7)
26.0 (25.0)
—
—
Br2, 2.6 (16.3)
35.6 (29.1)
30.1 (23.3)
aReaction mixtures were taken from experiments, which are given in Table 1. bAccording to 19F NMR spectra. c22.3 mmol of organozinc compounds
(run 3, Table 1) was used for the reaction with Br2. The rest of solution was treated with 10% HCl to give 0.49 g of a mixture of 3 and 5 in a ratio of 38:62
(
19F NMR). d15 ml of 10% HCl was used. eRatio 5:3.
chloride ions and subsequent formation of organometallics from
the corresponding 4-chloro derivative appears to be unlikely.
We also found that octafluorotoluene 9 reacts with Zn in DMF
in the presence of SnF2, i.e., in the absence of chloride ions, to
give bis(4-heptafluorotolyl)zinc 10; the latter was treated with
bromine to give 4-bromoheptafluorotoluene 11 in a good yield.
The reaction took place with Zn–Sn powder mixture but
occured slowly. Without addition of Sn, organozinc compound
10 is formed from 9 and Zn in a very small yield.†††
F
SnYa,b
Cl
F
Sns
F
F
Cl
F
F
F
Cl
F
F
F
Sns
F
CF3
CF3
CF3
ZnYb
The formation of organozinc compounds 2 in the reaction of 1
with Zn in the absence of SnCl2 can be rationalised by a radical
anion process by analogy with the mechanism of formation of
Grignard reagents and organozinc compounds.3,4
At the same time, the influence of the addition of SnCl2 on
the main route of the reaction of 1 with the participation of a
C–F bond would be expected to take place as a result of the
contribution of a nucleophilic mechanism. A possible route is
shown in Scheme 3. A concerted mechanism is also likely (cf.
ref. 5). It is known that octafluorotoluene is much more reactive
than chloropentafluorobenzene in nucleophilic reactions.6 In this
connection, a nucleophilic mechanism for chloropentafluoro-
F
F
Cl
F
Zn
CF3
Ya = Sns, F
Yb = Cl, 3-CF3C6F4, 2-Cl-4-CF3C6F3
Scheme 3
benzene seems incompetitive with a radical anion process and
only the C–Cl bond of chloropentafluorobenzene takes part in
the reaction. As a result of a nucleophilic attack, intermediate
organostannane compounds could be formed; they are probably
converted into organozinc compounds. A similar mechanism
could be suggested for the reaction of toluene 9 with Zn and SnF2.
†††Reaction of octafluorotoluene 9 with Zn–SnF2, Zn–Sn and Zn. The
mixture of Zn (4.05 g, 62.0 mmol), SnF2 (0.20 g, 1.3 mmol), toluene 9
(3.00 g, 12.7 mmol) was placed in closed flask (10 ml), magnetically
stirred at 70 °C for 8 h and then stored overnight. According to 19F NMR,
the starting compound converted completely. The main product was found
to be bis(4-heptafluorotolyl)zinc 10.1 The obtained solution was added
to a solution of bromine (2.05 g, 12.8 mmol) in 1.4 ml of DMF. Steam
distillation gave 96.9% (GLC) 4-bromoheptafluorotoluene 11 in 90%
yield (3.39 g after drying over CaCl2). Reaction of 9 with Zn and Sn
(powder, 0.15 g, 1.26 mmol) was carried out under conditions of the
previous experiment. According to 19F NMR, a solution of fluoroaromatics
included 9 (77%) and 10 (19%) (per aromatic moiety). A mixture (2.32 g)
obtained by treatment with a solution of Br2 (0.88 g, 5.5 mmol) contained
30.7% (GLC) compound 11 and 63.8% compound 9; estimated yields
were 19 and 49%, respectively.
References
1 A. O. Miller, V. I. Krasnov, D. Peters, V. E. Platonov and R. Miethchen,
Tetrahedron Lett., 2000, 41, 3817.
2 V. I. Krasnov and V. E. Platonov, Zh. Org. Khim., 2000, 36, 1524 (Russ.
J. Org. Chem., 2000, 36, 1488).
3 B. J. Wakefield, in Comprehensive Organic Chemistry, ed. D. N. Jones,
Pergamon Press, Oxford, New York, Toronto, Sydney, Paris, Frankfurt,
1979, vol. 3, p. 975.
4 A. Guijarro, D. M. Rosenberg and R. D. Rieke, J. Am. Chem. Soc., 1999,
121, 4155.
5 M. I. Slaked, T. Broun, B. Newmann and H.-G. Stammler, New J. Chem.,
2003, 27, 313.
6 G. M. Brooke, J. Fluorine Chem., 1997, 86, 1.
Reaction of 9 with Zn was performed by the above procedure. The
reaction mixture contained compound 10 (2%) (per aromatic moiety)
and compound 9 (95%). Bromine (0.40 g, 2.50 mmol) was added to the
solution. The above treatment resulted in the mixture (2.63 g) containing
4.5% compound 11 and 90.6% compound 9 (yields by NMR: 3 and 80%,
respectively).
Received: 1st November 2005; Com. 05/2608
170 Mendeleev Commun. 2006