New Access to Chloro- and Fluoroaromatics
J . Org. Chem., Vol. 63, No. 8, 1998 2495
formate,15d and 2-isopropylphenyl chloroformate15e were pre-
pared from the corresponding phenols by literature procedures.
2,6-Dim eth yl-4-br om op h en yl Ch lor ofor m a te. The title
compound was prepared from 2,6-dimethyl-4-bromophenol by
a method analogous to the previously described synthesis of
2,6-dimethylphenyl chloroformate15b in 63% yield upon recrys-
tallization from hexanes/diethyl ether (9:1) (mp ) 55-56 °C;1H
NMR δ 2.25 (s, 6H, 2CH3), 7.1 (3H, H-aromatic)).
Ta ble 4. Deca r boxyla tion of Ar om a tic Ch lor ofor m a tes
in HF a n d 1,2,4-Tr ich lor oben zen e to th e Cor r esp on d in g
F lu or oben zen es
Deca r b oxyla t ion of 2,6-Dim et h ylp h en yl Ch lor ofor -
m a te: Gen er a l P r oced u r e. Anhydrous Lewis acid (2-20
mol %) was added to 2,6-dimethylphenyl chloroformate (1)
(46.1 g, 0.25 mol) and then heated at 200 °C for the stated
time. The reaction mixture was then allowed to cool to room
temperature and then poured onto ice and extracted with
dichloromethane (3 × 150 mL). The combined organic extracts
were dried (MgSO4) and evaporated under reduced pressure
to give a brown oil that was purified by vacuum distillation to
give the pure 1-chloro-2,6-dimethylchlorobenzene: bp 70-74
°C/5 mbar; NMR data were in agreement with published
data.16a
T
(°C)
yielda
(%)
entry
R1
R2
R3
R4
1
2
3
4
5
6
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
110
110
150
140
150
200
72
0b
76
90
70
0
CH3
CH3
CH3
CH3
CH3
Br
a
b
Isolated yield. The corresponding fluoroformate was isolated
in greater than 90% yield.
Deca r boxyla tion of Ar yl Ch lor ofor m a tes w ith ou t Sol-
ven t: Gen er a l P r oced u r e. Anhydrous aluminum chloride
(0.006 mol) was added to the phenyl chloroformate (1) (0.27
mol) and then heated to 200 °C. Above 180 °C, the evolution
of carbon dioxide commenced and heating was continued until
the evolution stopped (ca. 210 min). The reaction mixture was
worked up as described above. All NMR data were in
agreement with published data: 1-chloro-2,4,6-trimethylben-
zene,16b 2,4-dimethylchlorobenzene,16c 1-chloro-2,3-dimethyl-
benzene,16d and 1-chloro-2-isopropylbenzene.16e
Sch em e 3
Deca r boxyla t ion of Ar yl Ch lor ofor m a t es in 1,2,4-
Tr ich lor oben zen e. Gen er a l P r oced u r e. Anhydrous alu-
minum chloride (0.05 mol) was added to a solution of the
phenyl chloroformate 1 (2.5 mol) in 1,2,4-trichlorobenzene (600
mL) and then heated to 200 °C. Above 180 °C, the evolution
of carbon dioxide commenced, and heating was continued until
the evolution stopped (210 min). The mixture was worked up
as above.
The first step of the reaction is fluorination of the
phenylchloroformate by the HF, indicated by the isolation
of 2,3-dimethylphenylfluoroformate as the sole product
from the treatment of the corresponding chloroformate
at 100 °C (Table 4, entry 2). The temperature required
for the decarboxylation of the fluoroformate is dependent
on the nature, number, and position of substituents. The
more alkyl substituents present, the lower the decar-
boxylation temperature. For example, there is a 30 °C
difference between the decarboxylation temperature of
2,4,6-trimethyl- and 2,6-dimethylphenyl formate (Table
4, entries 1 and 2). The difference in the decarboxylation
temperature between 2,3- and 2,6-dimethylphenyl for-
mate indicates that substituents in the 2 and 6 positions
have the greatest effect on the decarboxylation temper-
ature. When an electron-withdrawing substituent such
as a bromine atom is present, the stability of the phenyl
fluoroformate is such that decarboxylation does not occur
below 200 °C, the practical limit of our procedure (Table
4, entry 6). Finally, the treatment of 2-methoxyphenyl
chloroformate with HF under identical conditions did not
give the desired fluorinated aromatic compound, but
instead benzo[1,3]dioxol-2-one (4) (Scheme 3).
Syn th esis of 2,6-Dim eth ylp h en yl F lu or ofor m a te. An-
hydrous potassium fluoride (50 g, 0.86 mol) was added por-
tionwise to a stirred solution of 2,6-dimethylphenyl chlorofor-
mate (100 g, 0.54 mol) and 18-crown-6 (7 g, 0.26 mol) in
dichloromethane (250 mL) at room temperature. After 5 h,
the suspension was filtered, and the resulting solution was
then evaporated under reduced pressure to give a colorless oil
that was purified by vacuum distillation to give the pure 2,6-
dimethylphenyl fluoroformate (bp 59-63 °C/16 mbar) in 80%
-1
1
yield: IR (neat) 1842 cm
;
19F NMR δ 16.4; H NMR δ 2.25
(s, 6H, 2 CH3), 7.1 (3H, H-aromatic).
Syn th esis of 2,6-Dim eth ylflu or oben zen e by th e SbF 5-
Ca ta lyzed Deca r boxyla tion of 2,6-Dim eth ylp h en yl F lu o-
r ofor m a te. A stirred mixture of anhydrous SbF5 (17.6 g,
0.059 mol) and 2,6-dimethylphenyl fluoroformate (100 g, 0.59
mol) was heated to 185 °C. Above 180 °C, the evolution of
carbon dioxide commenced, and heating was continued until
the evolution stopped (180 min). The reaction mixture was
then allowed to cool to room temperature and then poured onto
ice and extracted with dichloromethane (3 × 150 mL). The
combined organic extracts were dried (MgSO4) and evaporated
under reduced pressure to give a black oil that was purified
by vacuum distillation to give the pure 1-chloro-2,6-dimeth-
ylfluorobenzene: bp ) 80-82 °C/20 mBar; NMR data were in
agreement with published data.16a
Exp er im en ta l Section
(15) (a) Pattison, V. A.; Colson, J . G.; Carr, R. L. K. J . Org. Chem.
1968, 33, 1084-1087. (b) Zabik, M. J .; Schuetz, R. D. J . Org. Chem.
1967, 32, 300-307. (c) Pickard, R. H.; Littlebury, W. O. J . Chem. Soc.
1907, 91, 302-307. (d) Barnes, J . H. J . Pharm. Pharmacol. 1961, 13,
39-48. (e) Altner, W.; Meisert, E.; Rockstroh, G. German Patent
1,117,589, 1961; Chem. Abstr. 1962, 57, 11106d.
(16) (a) J enneskens, L. W.; De Wolf, W. H.; Bickelhaupt, F. Synthesis
1985, 647-649. (b) Brown, F.; Bruyne, J . M. A.; Gross, P. J . Am. Chem.
Soc. 1934, 56, 1-93. (c) Socrates, G.; Adlard, M. W. J . Chem. Soc B,
1971, 733-736. (d) Hopff, H.; Gallegra, P. Helv. Chim. Acta 1968, 51,
253-260. (e) Beak, P.; Trancik, R. J .; Simpson, D. A. J . Am. Chem.
Soc. 1969, 91, 5073-5086.
NMR spectra were performed in CDCl3 solution on a Bruker
AC 200 and ARX 400 (1H, 200 or 400 MHz; 19F, 188 or 376
MHz). Chemical shifts are reported in ppm relative to Me4Si
and CFCl3 (for 19F NMR) as internal standards. GC analysis
was performed on capillary columns SE30, 10 or 25 m. All
reagents were used as supplied, without further purification.
Syn th esis of Ar yl Ch lor ofor m a tes. 2,6-Dimethylphenyl
chloroformate,15a 2,4,6-trimethylphenyl chloroformate,15b 2,4-
dimethylphenyl chloroformate,15c 2,3-diimethylphenyl chloro-