PROCESS FOR THE SELECTIVE DEHALOGENATION OF ORTHO-HALOGENONITROBENZENES

PROCEDE DE DESHALOGENATION SELECTIVE DES ORTHO-HALOGENONITROBENZENES

English Abstract

HOE 92/F 050
Abstract of the Disclosure:
Process for the selective dehalogenation of ortho-
halogenonitrobenzenes
The present invention relates to a novel process for the
selective dehalogenation of ortho-halogenonitrobenzenes,
halogen being chlorine, bromine or a combination thereof,
wherein, in nitrobenzenes of general formula (I):
<IMG> (I)
wherein X1 and X3 or X1 and X5 are in each case chlorine,
bromine or a combination thereof and the remaining
substituents X independently of one another are hydrogen,
fluorine or C1-C4-alkyl, the halogen atoms X1 and X5 are
each replaced with hydrogen atoms by reaction with copper
in the presence of a proton donor.
Access to the industrially relevant 4-chloro-3-fluoro-
nitrobenzene from 2,4-dichloro-3-fluoronitrobenzene or
2,4-dichloro-5-fluoronitrobenzene is of particular
interest.

Claims

- 9 - HOE 92/F 050
WHAT IS CLAIMED IS:
1. A process for the selective dehalogenation of ortho-
halogenonitrobenzenes, halogen being chlorine,
bromine or a combination thereof, wherein, in nitro-
benzenes of general formula (I):
<IMG> (I)
wherein X1 and X3 or X1 and X5 are in each case
chlorine, bromine or a combination thereof and the
remaining substituents X independently of one
another are hydrogen, fluorine or C1-C4-alkyl, the
halogen atoms X1 and X5 are each replaced with
hydrogen atoms by reaction with copper in the
presence of a proton donor.
2. The process as claimed in claim 1, wherein, in the
compound of formula (I), X1 and X3 or X1 and X5 are in
each case chlorine and X2 and X4 independently of one
another are hydrogen or fluorine.
3. The process as claimed in claim 1 or 2, wherein the
compound of formula (I) is 2,4-dichloro-3-fluoro-
nitrobenzene, 2,4-dichloro-5-fluoronitrobenzene or
2,6- dichloro-3,5-difluoronitrobenzene.
4. The process as claimed in at least one of claims 1
to 3, wherein, in nitrobenzenes of general formula
(I), the halogen atoms X1 and X5 are each replaced
with hydrogen atoms by reaction with copper and a

- 10 -
reducing agent whose potential is sufficient to
reduce copper salts to metallic copper, preferably
aliphatic aldehydes, in the presence of a proton
donor.
5. The process as claimed in claim 4, wherein the
aliphatic aldehyde is methanal, ethanal, propanal,
butanal or a mixture thereof.
6. The process as claimed in at least one of claims 1
to 5, wherein the proton donor used is an inorganic
acid, an aromatic monocarboxylic acid, an aromatic
dicarboxylic acid, an aromatic polycarboxylic acid,
an aliphatic monocarboxylic acid, an aliphatic
dicarboxylic acid, an aliphatic polycarboxylic acid
or a mixture thereof.
7. The process as claimed in at least one of claims 1
to 6, wherein the proton donor used is hydrochloric
acid, benzoic acid, phthalic acid, acetic acid,
propionic acid, malonic acid, succinic acid or a
mixture thereof.
8. The process as claimed in at least one of claims 1
to 7, wherein the reaction is carried out without
the addition of a solvent.
9. The process as claimed in at least one of claims 1
to 7, wherein the reaction is carried out in the
presence of an organic solvent which is inert
towards the reaction in question, preferably
benzene, toluene, xylene, dichlorobenzene, dichloro-
toluene, decalin, nitrobenzene or a mixture thereof.
10. The process as claimed in at least one of claims 1
to 7, wherein the reaction is carried out in the
presence of nitrobenzene.

- 11 -
11. The process as claimed in at least one of claims 1
to 10, wherein the proton donor is used in amounts
less than the stoichiometric amounts, based on the
ortho-halogenonitrobenzene used.

Description

2~90280
HOECHST AKTIENGESELLSCHAFT HOE 92/F 050 Dr. HU/PL
Description
..
Proces for the selective dehalogenation of ortho-
halogenonitrobenzenes
The present invention relates to a novel process for the
selective dehalogenation of nitrobenzenes containing one
or two chlorine or bromine atoms in the 2- and/or 6-
position relative to the nitro group.
Industrial access to 4-chloro-3-fluoronitrobenzene is
greatly restricted with the synthetic routes
conventionally used hitherto. Thus, for example, the
nitration of 2-fluorochlorobenzene leads to a mixture of
79% of 3-chloro-4-fluoronitrobenzene and only 21% of 4-
chloro 3-fluoronitrobenzene (Houben-Weyl, Methoden der
Organischen Chemie (Methods of Organic Chemistry), 4th
edition, vol. X/1, p. 507). A Sandmeyer reaction is also
unattractive for the preparation of 4-chloro-3- fluoro-
nitrobenzene on the industrial scale because of the
expensive 6ynthesis of the starting material 2- fluoro-
4-nitroaniline.
Japanese patent disclosure Sho-63 156 757 describQs a
process for the selective dehalogenation of fluorinated
ortho-chloronitrobenzenes with the aid of sodium boro-
hydride, although this is too expensive for industrial
u~e.
There was therefore considerable interest in a novel,
economically sen~ible route to the preparation of halo-
genated nitrobenzenes which are selectively dehalogenated
in the 2- and 6-position relative to the nitro group,
especially for the preparation of 4-chloro-3- fluoro-
nitrobenzene, which is a precursor for 3,4-difluoro-
nitrobenzene (US-P5 4,036,977; US-PS 4,12n,099; US-PS 4,130,561
and US-PS 4,200,588).
.:
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209~2~0
-- 2 --
It is known that 2-chloronitrobenzene, but not 3-chloro-
nitrobenzene or 4-chloronitrobenzene, can be reductively
dechlorinated to nitrobenzene with copper in benzoic acid
(W.T. Smith Jr., J. Amer. Chem. Soc., 71, 2852 (1949)).
Later, this author also describes the reductive dehalo-
genation of 2,5-dichloronitrobenzene and 2,5-dibromo-
nitrobenzene to 3-chloronitrobenzene and 3-bromonitro-
benzene, respectively, in moderate yields of 37 - 38%
(W.T. Smith Jr. and L. Campanaro, J. Amer. Chem. Soc.,
75, 3602 (1953)). He further proves that monofluoronitro-
benzenes cannot be reductively defluor.inated with
copper/benzoic acid. By contrast, nothing was known about
the behavior of nitrobenzenes containing chlorine or
bromine atoms in the 2- and 4-position or in the 2- and
6-position relative to the nitro group. Because the
electronic conditions in the benzene ring change
substantially when additional chlorine or bromine atoms
are present or the position of these halogen atoms in the
ring alters, it could not be assumed that the method of
Smith et al. was suitable for the preparation of 4-
chloro-3-fluoronitrobenzene.
It has been found, surprisingly, that both 2,4-di-
halogenonitrobenzenes and 2,6-dihalogenonitrobenzenes,
halogen being chlorine, bromine or a combination thereof,
can be selectively dehalogenated in the ortho-
position(s) relative to the nitro group u8ing copper with
the addition of a proton donor.
Furthermore, it has been found, surprisingly, that the
addition of suitable reducing agents makes it possible to
cut down the amounts of metallic copper required. The
potential of the reducing agents here must be
sufficiently high to be able to reduce the copper salts
formed in the dehalogenation to metallic copper.
-
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2090280
-- 3 --
The present invention relates to a process for the
selective dehalogenation of ortho-halogenonitrobenzenes,
halogen being chlorine, bromine or a combination thereof,
wherein, in nitrobenzenes of general formula (I):
N02
X 5\ /1, /X
Js 3 ~ (I)
X4 \ j / X2
wherein X~ and X3 or Xl and X5 are in each case chlorine,
bromine or a combination thereof and the remaining
substituents X independently of one another are hydrogen,
fluorine or Cl-C4-alkyl, the halogen atoms X~ and X5 are
each replaced with hydrogen atoms by reaction with
copper, preferably in the presence of a reducing agent
capable of reducing copper salts to metallic copper, and
in the presence of a proton donor.
Compounds of formula (I) which are of special interest
here are those in which Xl and X3 or X~ and X5 are in each
case chlorine and x2 and X4 independently of one another
are hydrogen or fluorine.
of particular intere~t are the compounds 2,4-dichloro- 3-
fluoronitrobenzeneand2,4-dichloro-5-fluoronitrobenzene,
which can be converted to 4-chloro-3-fluoronitrobenzene,
selectively and in good yields, by the process according
to the invention~
Also of interest is the compound 2,6-dichloro-3,5-di-
fluoronitrobenzene, which is converted to 3,5-difluoro-
:

~0280
-- 4 --
nitrobenzene by the process according to the invention.In no case does defluorination take place; likewise,
dechlorination does not occur in the para- or meta-
position relative to the nitro group.
In the process according to the invention, the addition
of suitable reducing agents can cut down the amount of
metallic copper required by up to 90~, preferably up to
60~. Suitable reducing agents are any substances whose
redox potential is sufficient to reduce the copper salts
formed in the dehalogenation to metallic copper. Possible
reducing agents in terms of the invention are aldehydes,
reducing sugars, polyalcohols and hydroquinones.
Particularly suitable reducing agents, however, are
aliphatic aldehydes, especially methanal, ethanal,
propanal and butanal, compounds which release methanal or
ethanal, such as trioxane, paraformaldehyde and polyoxy-
methylene, or a mixture of these compounds.
Proton donors which can be used in the process according
to the invention are both inorganic acids, preferably
hydrochloric acid, and aromatic monocarboxylic acids,
preferably benzoic acid, aromatic dicarboxylic acids,
preferably phthalic acid, aromatic polycarboxylic acids
and aliphatic monocarboxylic acids, preferably methane-
carboxylic acid, ethanecarboxylic acid, propanecarboxylic
acid and butanecarboxylic acid, aliphatic dicarboxylic
acids, preferably malonic acid and succinic acid, and
aliphatic polycarboxylic acids, as well as combinations
thereof. The amounts of proton- providing compounds used
can be either equal to or greater than or less than the
stoichiometric amounts. ~he use of amounts less than the
stoichiometric amounts is favorable in all cases where
the copper ~alts formed dissolve in the excess acid and
hence make the working- up more difficult.
The process according to the invention can be carried out
either with or without the addition of a solvent.

2 ~
Convenient organic solvents are all those which are inert
towards the reaction according to the invention and which
have a high boiling point, preferably benæene, toluene,
xylene, dichlorobenzene, dichlorotoluene or decalin, but
especially nitrobenzene. The addition of a solvent,
especially nitrobenzene, can considerably increase the
yield when benzoic acid is used.
The upper limit of the reaction temperature is governed
only by the stability of the carboxylic acids used in the
presence of copper. Said temperature can be within a very
wide range from about 80 to about 300C, preferably 140
to 240C. The reaction according to the invention can be
carried out at atmospheric pressure or under excess
pressure in an autoclave.
In the Examples which follow, percentages are always by
weight. The products were identified with the aid of gas
chromatographic analyses.
Examples
1) Preparation of 4-chloro-3-fluoronitrobenzene from
2,4-dichloro-3-fluoronitrobenzene
209.7 g (3.3 mol) of copper powder were suspended in
portions at 150C in a ~olution of 630 g (2.7 mol) of
2,4-dichloro-3-fluoronitrobenzene (90%; contains 10% of
3,5-dichloro-4-fluoronitrobenzene) and 402.6 g (3.3 mol)
of benzoic acid in 600 g of nitrobenzene, with stirring.
When the addition was complete, stirring was continued
for 4 hours, the suspension was filtered with suction,
the solid was washed twice with in each case 100 g of
nitrobenzene and the combined mother liquors were
fractionated to give 355.6 g (83% of theory) of 4-
chloro-3-fluoronitrobenzene together with 55 g of
'
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2~28~
-- 6 --
unreacted 3,5-dichloro-4-fluoronitrobenzene and 91 ~ of
unreacted 2,4-dichloro-3-fluoronitrobenzene.
2) Preparation of 4-chloro-3-fluoronitrobenzene from
2,4-dichloro-5-fluoronitrobenzene
à) 241.5 g (3.8 mol) of copper powder were suspended in
portions at 150C in a solution of 630 g (3.0 mol) of
2,4-dichloro-5-fluoronitroben~ene and 463.6 g (3.8 mol)
of benzoic acid in 600 g of nitrobenzene, with ~tirring.
When the addition was complete, stirring was continued
for 4 hours, the resulting suspension was filtered with
suction, the solid was rinsed twice with in each case
200 g of nitrobenzene and the combined mother liquor was
washed with 200 g of 10~ sodium hydroxide solution and
then with 200 g of water, dried over sodium sulfate and
15 fractionated to give 362.3 g (69% of theory) of 4-
chloro-3-fluoronitrobenzene and 104 g of unreacted 2,4-
dichloro-5-fluoronitrobenzene.
b) 420 g (2.0 mol) of 2,4-dichloro-5-fluoronitrobenzene
were placed at lS0C in a 1 1 round-bottomed flask
equipped with a stirrer, a reflux condenser, an internal
thermometer and a dropping funnel with stirrer, and a
suspension of 158.9 g (2.5 mol) of copper powder in 296
g (4 mol) of propionic acid was added dropwise over one
hour. The mixture was then heated for 3 hours at 150C
and the excess propionic acid was distilled off. The
resulting suspension was filtered with suction, the
residue waY rinsed with nitrobenzene and the mother
liquor was fractionatQd to give 247.6 g (71% of theory)
of 4-chloro-3-fluoronitrobenzene and 70.1 g of unreacted
2,4-dichloro-S-fluoronitrobenzene.
c) 52.5 g (0.25 mol) of 2,4-dichloro-5-fluoronitrobenzene
and 14.5 g (0.25 mol) of propionaldehyde were placed in
a glass autoclave equipped with a stirrer and an internal
thermometer, 4.5 g (0.07 mol) of copper powder were
35 suspended therein, 9.3 g (0.13 mol) of propionic acid and
.
.

2~2~0
6.0 g (0.3 mol) of water were added and the mixture was
heated for 6 h at approx. 155C, with stirring. ~11 the
constituents volatile up to 80C/ 0.06 bar were then
distilled off, the resulting suspension was filtered with
suction and the mother liquor was fractionated to give
15.3 g (125% based on copper used) of 4-chloro-3-fluoro-
nitrobenzene together with 23.1 g of unreacted 2,4-
dichloro-5-fluoronitrobenzene.
d) A suspension of 210.1 g (1.0 mol) of 2,~-dichloro-5-
fluoronitrobenzene, 63.6 g (1.0 mol) of copper powder, 74
g (1.0 mol) of propionic acid and 1250 g of nitrobenzene
was prepared in a 4 1 enamel autoclave equipped with a
stirrer, a nitrogen pressure of approx. 2 bar was
established and the mixture was heated for 5 hours at
170C. According to gas chromatographic analysis, the
conversion to 3-fluoro-4-chloronitrobenzene after this
time was 74.3%.
e) A suspension of 210.1 g (1.0 mol) of 2,4-dichloro-5-
fluoronitrobenzene, 63.6 g (1.0 mol) of copper powder,
60.1 g (1.0 mol) of acetic acid and 1250 g of nitro-
benzene was prepared in a 4 1 enamel autoclave equipped
with a stirrer, a nitrogen pressure of approx. 2 bar was
established and the mixture was heated for 12 hours at
170C. According to gas chromatographic analysis, the
conversion to 3-fluoro-4-chloronitrobenzene after this
time was 50.4~.
f) A su~pen~ion of 210.1 g (1.0 mol) of 2,4-dichloro-5-
fluoronitrobenzene, 63.6 g (1.0 mol) of copper powder,
100 g (1.0 mol) of 37~ hydrochloric acid and 1250 g of
nitrobenzene was prepared in a 4 1 enamel autoclave
equipped with a stirrer, a nitrogen pressure of approx.
2 bar was established and the mixture was heated for 12
hours at 170C. According to gas chromatographic
analysis, the conversion to 3-fluoro-4-chloronitrobenzene
after this time was 22.5%.
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2~28~
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3) Preparation of 3,5-difluoronitrobenzene from 2,6-
dichloro-3,5-difluoronitrobenzene
A total of 2.5 g (40 mmol~ of copper powder was added in
portions at 150C to a solution of 4.6 g (20 mmol) of
2,6-dichloro-3,5-difluoronitrobenzene and 3.0 g (40 mmol)
of propionic acid in 20 g of nitrobenzene, with stirring,
and stirring was continued for 3 hours at 150C. The
conversion to 3,5-difluoronitrobenzene after this time
was over 60~ (GC).