Fluorobenzoates and process for their production

A fluorobenzoate having the formula: ##STR1## wherein X is a fluorine atom or a hydrogen atom, and R is an alkyl group.

The present invention relates to novel fluorobenzoates and a process for 
their production. 
In recent years, an attention has been drawn to fluorine-containing 
agricultural chemicals and medicines as they have excellent 
pharmacological or physiological activities. They have been positively 
studied. For example, fluorine-containing urea insecticides and 
fluorine-containing quinolone germicides have been proposed. Among them, 
N-(3,5-dichloro-2,4-difluorophenyl)-N'-(2,6-difluorobenzoyl)urea disclosed 
in Japanese Unexamined Patent Publication No. 126460/1982 is known to have 
high activities as an insecticide. Further, as a method for its 
production, it is known to react 3,5-dichloro-2,4-difluorophenyl 
isocyanate with 2,6-difluorobenzamide. 
The fluorophenyl isocyanate used in the method disclosed in the above 
publication is prepared usually by reacting the corresponding aniline with 
phosgene. However, phosgene is a poisonous gas, and its use is restricted 
by regulations. Under the circumstances, it has been desired to develop a 
method for producing the phenyl isocyanate without using phosgene. As a 
method for producing an isocyanate without using phosgene, it has been 
recently proposed to fluorinate 2,3,4,5-tetrachlorobenzoyl chloride to 
obtain 3,5-dichloro-2,4-difluorobenzoyl fluoride, which is reacted with 
sodium azide to obtain the corresponding benzoyl azide, which is then 
heated to obtain 3,5-dichloro-2,4-difluorophenyl isocyanate (International 
Patent Application published under WO86/05487). However, this method 
employs explosive sodium azide, and is therefore not satisfactory for 
practical industrial application. 
Under these circumstances, the present inventors have conducted extensive 
researches to develop a method for producing a fluorophenyl isocyanate in 
a different manner on an industrial scale. As a result, it has been found 
that when the corresponding chlorobenzoate is reacted with a metal 
fluoride in the presence of a certain specific catalyst in a certain 
specific solvent or in the absence of a solvent, a novel fluorobenzoate 
can be produced while suppressing a side reaction of the ester group, and 
further that the above-mentioned fluorophenyl isocyanate can be produced 
from this fluorobenzoate. The present invention has been accomplished on 
the basis of these discoveries.

The present invention provides a fluorobenzoate having the formula: 
##STR2## 
wherein X is a fluorine atom or a hydrogen atom, and R is an alkyl group, 
which is useful as an intermediate for the production of 
fluorine-containing urea insecticides or fluorine-containing quinolone 
germicides. 
Further, the present invention provides a process for producing a 
fluorobenzoate of the formula I, which comprises reacting a chlorobenzoate 
having the formula: 
##STR3## 
wherein Y is a hydrogen atom or a chlorine atom, and R is as defined 
above, with a metal fluoride. The reaction is conducted either in an 
aprotic polar solvent in the presence of at least one salt selected from 
the group consisting of quaternary phosphonium salts, quaternary ammonium 
salts and pyridinium salts, as catalyst, or in the presence of a 
combination of at least one salt selected from the group consisting of 
quaternary phosphonium salts, quaternary ammonium salts and pyridinium 
salts, and at least one compound selected from the group consisting of 
crown ethers and polyalkylene glycols, as catalyst. 
Now, the present invention will be described in detail with reference to 
the preferred embodiments. 
The fluorobenzoate of the present invention is a compound of the formula I 
wherein X is a hydrogen atom or a fluorine atom, and R is an alkyl group, 
preferably a C.sub.1 -C.sub.5 alkyl group such as a methyl group, an ethyl 
group, a propyl group, an isopropyl group, a t-butyl group, a sec-butyl 
group or a neopentyl group. Such a fluorobenzoate includes, for example, 
methyl 3,5-dichloro-4-fluorobenzoate, ethyl 3,5-dichloro-4-fluorobenzoate, 
isopropyl 3,5-dichloro-4-fluorobenzoate, t-butyl 
3,5-dichloro-4-fluorobenzoate, sec-butyl 3,5-dichloro-4-fluorobenzoate, 
neopentyl 3,5-dichloro-4-fluorobenzoate, methyl 
3,5-dichloro-2,4-difluorobenzoate, ethyl 
3,5-dichloro-2,4-difluorobenzoate, isopropyl 
3,5-dichloro-2,4-difluorobenzoate, t-butyl 
3,5-dichloro-2,4-difluorobenzoate, sec-butyl 
3,5-dichloro-2,4-difluorobenzoate and neopentyl 
3,5-dichloro-2,4-difluorobenzoate. 
The chlorobenzoate used as a starting material in the process for the 
production of a fluorobenzoate of the present invention is a compound of 
the formula II wherein Y is a hydrogen atom or a chlorine atom, and R is 
an alkyl group, preferably a C.sub.1 -C.sub.5 alkyl group such as a methyl 
group, an ethyl group, a propyl group, an isopropyl group, a t-butyl 
group, a sec-butyl group or a neopentyl group. Particularly preferred as R 
is a neopentyl group. Such a chlorobenzoate includes, for example, methyl 
3,4,5-trichlorobenzoate, ethyl 3,4,5-trichlorobenzoate, isopropyl 
3,4,5-trichlorobenzoate, t-butyl 3,4,5-trichlorobenzoate, sec-butyl 
3,4,5-trichlorobenzoate, neopentyl 3,4,5-trichlorobenzoate, methyl 
2,3,4,5-tetrachlorobenzoate, ethyl 2,3,4,5-tetrachlorobenzoate, isopropyl 
2,3,4,5-tetrachlorobenzoate, t-butyl 2,3,4,5-tetrachlorobenzoate, 
sec-butyl 2,3,4,5-tetrachlorobenzoate and neopentyl 
2,3,4,5-tetrachlorobenzoate. 
The quaternary phosphonium salts, the quaternary ammonium salts and the 
pyridinium salts used as catalyst in the process of the present invention 
may be compounds represented by the following formulas III, IV and V, 
respectively. 
##STR4## 
wherein each of R.sup.1, R.sup.2, R.sup.3 and R.sup.4 which may be the 
same or different is an alkyl group, an aryl group or an aralkyl group, X' 
is a halogen atom, each of R.sup.5, R.sup.6 and R.sup.7 which may be the 
same or different is an alkyl group, and X" is a halogen atom. 
Specific examples of such compounds include quaternary phosphonium salts 
such as tetraphenyl phosphonium bromide, tetraphenyl phosphonium chloride, 
benzyltributyl phosphonium chloride, benzyltriphenyl phosphonium chloride 
and triphenylmethyl phosphonium chloride; quaternary ammonium salts such 
as tetramethylammonium chloride, tetraethylammonium bromide, 
tetrabutylammonium bromide, tetrabutylammonium iodide, tetrahexylammonium 
bromide, tetraoctylammonium chloride, ethyltrimethylammonium chloride, 
butyltriethylammonium chloride, lauryltrimethylammonium bromide, 
ethyltributylammonium bromide, isobutyltributylammonium bromide, 
hexyltributylammonium bromide, octyltributylammonium bromide, 
lauryltributylammonium bromide, methyltrioctylammonium bromide, 
tetraphenylammonium chloride, benzyltrimethylammonium bromide, 
benzyltriethylammonium chloride, benzyltripropylammonium chloride, 
benzyltrihexylammonium chloride and benzyltrioctylammonium chloride; and 
pyridinium salts such as N-(2-ethylhexyl)-4-dimethylaminopyridinium 
chloride, N-(2-ethylhexyl)-4-di-n-butylaminopyridinium chloride, 
N-(2-ethylhexyl)-4-di-n-hexylaminopyridinium chloride, 
N-neopentyl-4-dimethylaminopyridinium chloride, 
N-neopentyl-4-di-n-butylaminopyridinium chloride, 
N-neopentyl-4-di-n-hexylaminopyridinium chloride, 
N-(2-ethylhexyl)-4-dimethylaminopyridinium chloride, 
N-(2-ethylhexyl)-4-di-n-butylaminopyridinium bromide, 
N-(2-ethylhexyl)-4-di-n-hexylaminopyridinium bromide, 
N-neopentyl-4-dimethylaminopyridinium bromide, 
N-neopentyl-4-di-n-butylaminopyridinium bromide and 
N-neopentyl-4-di-n-hexylaminopyridinium bromide. 
Further, in the present invention, a combination of at least one salt 
selected from the group consisting of the above quaternary phosphonium 
salts, quaternary ammonium salts and pyridinium salts and at least one 
compound selected from the group consisting of crown ethers and 
polyalkylene glycols may be used as catalyst. 
The crown ethers include, for example, 18-crown-6, dibenzo-18-crown-6, 
dicyclohexano-18-crown-6, 12-crown-4,15-crown-5 and dibenzo-24-crown-8. 
Among them, 18-crown-6, dibenzo-18-crown-6 and dicyclohexano 18-crown-6 
are particularly preferred. 
As the polyalkylene glycols, compounds of the formula: 
EQU R.sup.9 O(R.sup.8 O).sub.z R.sup.10 (V) 
wherein R.sup.8 is an alkylene group, each of R.sup.9 and R.sup.10 which 
may be the same or different is a hydrogen atom, an alkyl group, an aryl 
group or an aralkyl group, and z is an integer of at least 2 may be used. 
Such compounds include, for example, glycols such as diethylene glycol, 
triethylene glycol, tetraethylene glycol, pentaethylene glycol, 
hexaethylene glycol, diisopropylene glycol, dipropylene glycol, 
tripropylene glycol, tetrapropylene glycol and tetramethylene glycol; 
monoalkyl ethers such as monomethyl, monoethyl, monopropyl and monobutyl 
ethers of such glycols; dialkyl ethers such as tetraethylene glycol 
dimethyl ether and pentaethylene glycol dimethyl ether; phenyl ethers; 
benzyl ethers; and polyalkylene glycols such as polyethylene glycol 
dimethyl ether (average molecular weight: 300), polyethylene glycol 
dibutyl ether (average molecular weight: 300) and polyethylene glycol 
dimethyl ether (average molecular weight:400). Among them, compounds 
wherein both R.sup.9 and R.sup.10 are alkyl groups, aryl groups or aralkyl 
groups are preferred. 
In the present invention, such crown ethers or such polyalkylene glycols 
may be used alone or in combination as a mixture of two or more. Further, 
such a crown ether and such a polyalkylene glycol may be used in 
combination. 
In the present invention, the catalyst may be used usually in an amount 
within a range of from 1 to 50 mol %, preferably from 5 to 40 mol %, per 
mol of the chlorobenzoate of the formula II. When the crown ether or 
polyalkylene glycol and the quaternary phosphonium salt, quaternary 
ammonium salt or pyridinium salt are used in combination as the catalyst, 
the proportions of the two components are preferably such that the amount 
of the crown ether or polyalkylene glycol does not exceed 4 mol times of 
the amount of the quaternary phosphonium salt, quaternary ammonium salt or 
pyridinium salt. When the crown ether or polyalkylene glycol is used alone 
without the quaternary phosphonium salt, the desired fluorobenzoate does 
not substantially form. 
The metal fluoride used in the process of the present invention may be, for 
example, potassium fluoride or cesium fluoride. Particularly preferred is 
spray-dried conducted under atmospheric pressure. The reaction time is 
usually from 1 to 20 hours. 
As shown below, the novel fluorobenzoate obtained by the process of the 
present invention can be reacted with hydrazine by a conventional method 
to obtain the corresponding fluorobenzoyl hydrazide, which is further 
reacted with sodium nitrite to obtain the corresponding fluorobenzoyl 
azide, which is then heated to obtain the above-mentioned fluorophenyl 
isocyanate. Further, by reacting this fluorophenyl isocyanate with 
benzamide, it is possible to produce a fluorine-containing urea 
insecticide as disclosed in Japanese Unexamined Patent Publication No. 
126460/1982. 
##STR5## 
According to the process of the present invention, a chlorobenzoate of the 
formula II is reacted with a metal fluoride in the presence of the 
specific catalyst and the specific solvent, whereby it is possible to 
suppress side reactions such as transfer of the --OR group in the formula 
potassium fluoride. Such a metal fluoride is used preferably in an amount 
of from 1 to 2 times in equivalent to the chlorine atom to be substituted 
in the chlorobenzoate of the formula II. 
This reaction is conducted usually in the presence of a solvent to 
facilitate the reaction, or may be conducted in the absence of a solvent. 
When a solvent is used, it is preferred to use an aprotic polar solvent 
such as sulfolane, dimethyl sulfone, 1,3-dimethylimidazolin-2-one, 
dimethylformamide, N-methylpyrrolidone, tetramethyl urea or dimethyl 
sulfoxide. When at least one salt selected from the group consisting of 
the above-mentioned quaternary phosphonium salts, quaternary ammonium 
salts and pyridinium salts is used alone as the catalyst, the reaction is 
preferably conducted in an aprotic polar solvent. This aprotic polar 
solvent is used usually in an amount within a range of from 100 to 1000 g, 
preferably from 150 to 500 g, per mol of the halogenated benzoate of the 
formula II. 
This reaction is conducted usually at a temperature within a range of from 
150.degree. to 300.degree. C., preferably from 160.degree. to 200.degree. 
C. There is no particular restriction as to the reaction pressure, and the 
reaction may be conducted under atmospheric pressure or under positive 
pressure. When the reaction is conducted under positive pressure, the 
pressure is preferably at most 10 kg/cm.sup.2. From the industrial point 
of view, the reaction is preferably to the aromatic ring decarboxylation 
and formation of high boiling substances and to produce a fluorobenzoate 
of the formula I in an industrially feasible manner. Further, the 
fluorobenzoate obtained by this method is useful as an intermediate for 
the production of fluorophenyl isocyanate. 
Now, the present invention will be described in further detail with 
reference to Examples. However, it should be understood that the present 
invention is by no means restricted by such specific Examples. 
EXAMPLE 1 
Into a 50 ml three-necked flask equipped with a condenser and a stirrer, 
6.0 g (104 mmol) of spray-dried potassium fluoride (purchased from Morita 
Kagaku Kogyo K.K.), 1.7 g (4 mmol) of tetraphenyl phosphonium bromide, 12 
g of anhydrous sulfolane and 20 ml of toluene, and the mixture was heated 
and stirred in an oil bath to distill off toluene and to conduct 
azeotropic removal of water. The mixture was heated at 140.degree. C., and 
then the pressure was reduced to a level of 45 mmHg to distill off 
substantially all the remaining toluene. The content of the flask was 
cooled to 100.degree. C. and substituted by nitrogen gas. Then, 13.1 g (40 
mmol) of neopentyl 2,3,4,5-tetrachlorobenzoate was added thereto, and the 
mixture was reacted under a nitrogen gas atmosphere at 190.degree. C. 
under stirring for 15 hours. 
After completion of the reaction, the reaction mixture was cooled and after 
an addition of 100 ml of toluene, subjected to filtration to remove 
inorganic substances. The filtrate was washed three times with 200 ml of 
water. The toluene layer was dried over anhydrous sodium sulfate, and 
concentrated under reduced pressure by a rotary evaporator to obtain 11.0 
g of a brown oily substance. The oily substance thus obtained was 
distilled under reduced pressure to obtain 7.2 g of neopentyl 
3,5-dichloro-2,4-difluorobenzoate as a colorless oil. The yield was 61%. 
The analytical data of the infrared spectrum (hereinafter referred to 
simply as IR), the nuclear magnetic resonance spectrum (hereinafter 
referred to simply as NMR) and the mass spectrum (hereinafter referred to 
simply as Mass) of this compound are shown below. 
Boiling point: 115.degree.-117.degree. C./2 mmHg 
Melting point: 38.degree.-42.degree. C. 
IR (KBr): 1720(C=O), 1250(C-F)cm.sup.-1 
.sup.1 H-NMR .delta. (CDCl.sub.3): 7.93(dd,J=8.0Hz,8.0Hz,1H), 4.07(s,2H), 
1.07(s,9H) 
Mass m/e: 296(M.sup.+), 209(M.sup.+ --CH.sub.2 C)CH.sub.3).sub.3) 
EXAMPLE 2 
The reaction was conducted in the same manner as in Example 1 for 6 hours 
by using 8.9 g (30 mmol) of neopentyl 3,4,5-trichlorobenzoate instead of 
neopentyl 2,3,4,5-tetrachlorobenzoate in Example 1, 2.6 g (45 mmol) of 
spray-dried potassium fluoride, 1.3 g (3 mmol) of tetraphenyl phosphonium 
bromide and 9 g of anhydrous sulfolane. The post-treatment was conducted 
in the same manner, followed by distillation under reduced pressure to 
obtain 5.3 g of neopentyl 3,5-dichloro-4-fluorobenzoate. Further, the 
distillation residue was subjected to silica gel column chromatography and 
eluted with benzene to obtain 2.0 g of neopentyl 
3,5-dichloro-4-fluorobenzoate as slightly yellow plates. The combined 
yield was 87%. The physical properties are shown below. 
Boiling point: 137.degree.-140.degree. C./7 mmHg 
Melting point: 96.degree.-98.degree. C. 
IR (KBr): 1730(C=O), 1240(C-F)cm.sup.-1 
.sup.1 H-NMR .delta. (CDCl.sub.3): 7.85(d,J=6.0Hz,2H), 3.97(s,2H) 
1.03(s,9H) 
Mass m/e: 278(M.sup.+), 191(M.sup.+ --CH.sub.2 C(CH.sub.3).sub.3) 
EXAMPLE 3 
The reaction and post-treatment were conducted in the same manner as in 
Example 1 except that 9.9 g (30 mmol) of neopentyl 
2,3,4,5-tetrachlorobenzoate, 4.0 g (69 mmol) of spray-dried potassium 
fluoride and 9 g of sulfolane were employed, and instead of tetraphenyl 
phosphonium bromide in Example 1, 0.8 g (3 mmol) of 
N-(2-ethylhexyl)-4-dimethylaminopyridinium chloride was used, whereby 5.7 
g of 3,5-dichloro-2,4-difluorobenzoate was obtained. The yield was 64%. 
EXAMPLE 4 
The operation was conducted in the same manner as in Example 2 except that 
0.8 g (3 mmol) of N-(2-ethylhexyl)-4-dimethylaminopyridinium chloride was 
used instead of tetraphenyl phosphonium bromide in Example 2, whereby 7.6 
g of neopentyl 3,5-dichloro-4-fluorobenzoate was obtained. The yield was 
91%. 
EXAMPLE 5 
Into a three-necked 50 ml flask equipped with a condenser and a stirrer, 
1.9 g (33 mmol) of spray-dried potassium fluoride (purchased from Laporte 
Industry), 1.1 g (2.5 mmol) of tetraphenyl phosphonium bromide, 0.7 g (2.5 
mmol) of 18-crown-6 and 6.4 g (25 mmol) of ethyl 3,4,5-trichlorobenzoate 
were introduced, and the mixture was heated in an oil bath and reacted 
under a nitrogen atmosphere at 210.degree. C. for 2 hours. The reactor was 
cooled, and the mixture was diluted with 40 ml of toluene. Inorganic salts 
were filtered off, and toluene was concentrated to give the residue, which 
was distilled under reduced pressure to obtain 3.4 g of ethyl 
3,5-dichloro-4-fluorobenzoate. The yield was 57%. The physical properties 
are shown below. 
Boiling point: 109.degree.-115.degree. C./5 mmHg 
Mass m/e: 236(M.sup.+), 208(M.sup.+ --CH.sub.2 .dbd.CH.sub.2)