Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
The present invention relates to an improved
process for the preparation of certain phenoxybenzoie acid
deriva-tives containlng a sulphonamide group, ~7hieh have
herbieidal properties.
Herbieidal derivatives of phenoxybenzole aeids
eontaining a sulphonamide group are known from European
Paten-t Applieations 3,416 and 23,392 published on 8th
Au~ust, 1979 and A-th Fe~ruary, 1981, respeetively.
These pa-tent applieations disclose products of
the formula:
C B R
D ~ ~ ~ ~ A (II~
E F
and their salts, in whieh formula:
A is hydrogen, fluorine, chlorine, bromine,
iodine, a n.i-tro groupr -N=NCF3, PO3H2 or an alkyl ester
-thereof having 1 to 4 carbon atoms, NH2, NHOH, N2, a carboxy
group or one of its funetional derivatives, a monoalkylamino
or dialkylam-no group, a group NH~CO-R , in whieh R is an
alkyl, alkoxy, monoalkyl.amino or dialkylamino radieal, an
alkyl group, trialkylammonio, NHSO2R , in which R is an
alkyl or phenyl radical, NHCONHSO2R , in which R is as
hereinbefore defined; alkylthio, alkylsulphinyl, alkyl-
sul.phonyl, dialkylsulphonio, cyano-
mab/lf`rl
sulphonyl, hydroxy, alkanoyloxy, alkoxy, alkoxy substitu-ted
by an alkoxycarbonyl group, SH, nitroso, -SCN, azide, CF3,
-N=N-P(OCH3)2 or acyl,
B is hydrogen, flllorirle, chlorine, bromine, iodine,
an alkyl, alkoxy, alkylsulphinyl or alkylsulphonyl group,
CF3, NO2, CN~ NH~, NHCOR , in which R is as :hereinbefore
defined, or CO~H2,
C is hydrogen, fluorine, chlorine, bromine, iodine
or an alkyl or dialkylamino group;
D is fluorine, chlorine, bromine, iodine or an
alkylthio, alkylsulphinyl, alkylsulphonyl, alkyl, halogeno-
alkyl, preferably CF3, sulphamoyl, formyl, alkylcarbonyl,
CN or dimethylamino group,
E is hydrogen, fluorine, chlorine, bromine, iodine,
an alkyl, alkoxy, alkylsulphinyl or alkylsulphonyl group,
CN, halogenoalkyl, preferably CF3, NH2, CONH2 or N~I-CO-R ,
wherein R is as hereinbefore defined,
F is as hereinbefore defined for B, and
R is a group -CO~(R )SO2R , in which:
R4 is hydrogen or an alkyl group having 1 to 4
carbon atoms, and
R is a phenyl, pyridyl or thienyl group optionally
substituted ~y one or more halogen atoms, ~lkyl groups
or nitro groups, an alkenyl or alkynyl radical having
2 to 4 carbon atoms, or an alkyl radical having 1 to 4
carbon atoms, which is optionally substituted by one or
more fluorine, chlorine, bromine or iodine atoms)
-- 3 --
preferably CF3, or by one or more of the following
substituents: carboxy, alkoxycarbonyl ha-~ing 2 to 5 carbon
atoms, alkylcarbonyl having 2 to 5 carbon atoms, monoalkyl-
carbamoyl or dialkylcarbamoyl, in which the alkyl groups have
from 1 to 4 carbon atoms, alko~y having 1 to h carbon atoms,
alkylthio, alkylsulphinyl, alkylsulphonyl, each having from
1 to 4 carbon atoms, alkylcarbonyloxy having 2 to 5 car~on
atoms, alkylcarbonylamino having 2 to 5 carbon atoms, or cyano.
In t~e above definitions, where reference is made
to alkyl radicals or radicals containing one or more alkyl
~roups, for example mono- and di-alkylamino, or alkoxy, the
alkyl radical may be for example a lower alkyl radical having
for example 1 to 6 carbon atoms.
In the known processes, the products of the -formula
(I) are prepared by reacting an intermediate acid halide of
the formula-
C B COX
D ~ -0- ~ A (II)
E F
wherein X is chlorine, bromine or iodine and A, B, C, D, E
and F are as hereinbefore defined, with a sulphonamide of
the formula: 3
2 2 (III)
wherein R3 is as hereir~efore defined, at from 25 to 140C, in
the presence of an acid accepto.r, in particular a tertiary
amine, such as ~,N-dimethylaniline or pyridine, an alkali
metal carbonate, such as anhydrous potassium c~rbonate, or
an alkali metal fluoride, such as caesium fluorideO
~ le compounds of formula (I) in which R4 is
hydrogen can be alkylated in a known manner, e.y. by
reaction with a diazoalkane having 1 to 4 carbon atoms, so
as to give the cc~rresponding products in which R4 is an
alkyl group ha~ing 1 to 4 carkon atoms.
The compounds of formula I in which, for exarnple,
R4 is a hydrogen atom are acids and form salts with bases:
such compounds may be converted in known manner into their
salts.
This process for the condensation of the products
of formulae ~II) and (III) has a number of disadvantages:
the yields are mediocre (e~g. it is possible to calculate a
yield of 27% for Example 14 of E-.lropean Patent Application
23,392 and of 9.5% for Example 34)O It is now considered
that it is the presence of the acid acceptor which lowers
the yield by promoting a diacylation reaction. Fur-thermore,
the use of an acid acceptor makes the final products more
difficult and more expensive to isolate and purify. An
object of the invention is to overcome these disadvantages.
The process accordlng to the invantlon comprises
reacting an acid halide of formula II wherein X, A, B, C, D,
E and F are as hereinbefore defined wi~h a sulphonamide of
formula (III), wherein R i,s as hereinbefore defined, in -the
absence of an acid acceptor and at a temperature at which the
gaseous hydrogen halide (HCl, HBr or HI) formed during the
reaction is eliminated from the reaction medium, as it is
-- 5 --
formed, the reaction temperature being be].ow the
decomposition temperature of the product of fo~mula (I)
~i.e~ the xeaction i5 carried out at a temperature at which
appreciable decomposition of the xeaction prvduct of the
formula (I) does not occur) and optionally converting in
known manner a compound thus obtained into a sal-t thereof
or converting in known manner a compound thus obtained
wherein R4 represents a hydrogen atom into a corresponding
compound wherein R4 represents an alkyl group having 1 to
carbon atoms~
By virtue of the process according -to the
invention, substantially higher yields of sulphonamide
derivatives of phenoxybenzoic acids can be obtained, eOg.
yields of at least about 30% and frequently of at least
about 50%, and with a much simpler me-thod of recovering and
purifying the final product than the methods of the kn~wn
processes.
It is pre-ferred to use an acid halide (preferably
the chloride) of formllla (II) in which A is the group ~2
or a fluorine, chlorine, bromine or iodine atom, B is a
halogen (preferably chlorine) atom, C, E and F are hydrogen
and D is the group CF3O It is also prefexred to use sulphon-
amides of formula (III) in which R3 is an alkyl group,
especially CH3l or a group CF3~
The temperature at which the process of the
invention can be carried out depends, in particular, on
whether either the acid halide of the formula (II~ or the
~ 6
sulphonamide of the formula (III) is in large excess, or
on whether or not a solvent having catalytic properties
is usedO
~he reaction may be carried out in the presence
of an excess of acid halide of formula (II). If the acid
halide ~II) is in large excess, i.eO the molar ratio (II)/
(III) is from about 1.5 to 5, as is preferred, the acid
halide (II) can serve as a solvent for the reaction and the
reaction temperature can be from 80 to 200C, but it is
then preferably from 90 to 160C.
~he unreacted acid halide (II) can be recovered
from the reaction medium by washing with an inert solvent,
such as a hydrocarbon, in particular pentane, hexane,
heptane, cyclopentane, cyclohexane, cycloheptane, benzene,
toluene or ~ylene, a halogenated hydrocarbon, in particular
chlorobenzenes, CS2, tetrahydrofuran, dioxane and the like~
~hen an excess of sulphonamide is used, for example
when the molar ratio of the compounds (III)/(II) is f.rom
1.5 to 5, the reaction temperature is then generally from 90
to 200C and preferably from 140 to 160C~ In any case, it
mu~st be at least sufficient to melt the reaction medium.
The excess sulphonamide (III) can be recovered from the
reaction medium by washing with water or another inert
solvent for this reactant ~III)~
~he reactants can also be dissolved in an inert
solvent havi.ng a boiling point above the reaction temperature,
e.g. a chlorinated or non-chlorinated liquid hydrocarbon,
such as benzene, toluene, xylenes, mixtures of xylenes or
~umene, the maximum reaction temperature is advantageously
slightly below the boiliny point of the solvent, Thus, in
the case of cumene, which boils at about 153C, the reaction
i5 preferably carried out at from 130 to 150C. me use of
an inert solvent has the practical advantage of permitting
better heat transfer in an in~ustrial-scale process, it
also makes it possible to avoid local overheating of the
reaction mediumO
According to another feature of the inventionl a
solvent is used which catalyses the reaction of the acid
halide (II) with the sulphonamide (III3 to give the phenoxy-
benzoylsulphonamide ~ Dimethylformamide (DMF, which boils
at about 154C) and dimethylacetamide (DMAC, which boils at
about 164C) are particu~arly advantageous in this respect,
and their use makes it possible to use relatively low
temperatures, e.g. from 80 to 120C, preferably from 90 -to
110C, or higher temperatures slightly below the boiling
point of these solvents; the reaction rate is then more
rapid. It is especially preferred to carry out the reaction
at a te~perature from 80C to -the boiling point of the
solvent, preferably at a temperature above 90Co
The following Examples illustrate the present
inventionO
-- 8 --
E~ample 1
Methanesulphonamide (2 g, On021 mol) is mixed
with 5-[2'-chloro-4'~(trifluoromethyl)-p~enoxy]-2-nitro-
benzoyl ~hloride (3.8 g; 0.01 mol). The mix-ture is heated
for 20 minutes at 150C. The hydrochloric acid is released
from the reaction medium as it is formed. ~ne medium is
cooled to give a black oil, which is dissolved in aque~us
sodium hydroxide solution; the solution is filtered and
the filtrate is acidified with dilute HCl, which precipitates
the product of the foxmula (IV~. ~his gave, with a yield of
71%, a product (3~1 g) meltiny at 195-197C and having an
in~ra-red absorption band at 1,692 cm 1 (C=0 group~ This
product has the ~ormula:
Cl ~ CO~NH-SO2-CH3
~< /~
3 ~ ~ NO2 (IV)
Example 2
Example 1 is repeated, but 250 g of acid chloride
and 130 g of me-thanesulphonamide are used. The reaction
product is isolated directly after the mixture has cooled~
by recrystallisation from isopropanol. This gives a
yield of 64% (785 g~ of the product of the formula (IVl.
The s-tructure of this product is confirmed by infra-red
(absorp-tion band at 1,692 cm ) and by nuclear magne-tic
resonance (singlet at 3,5 ppm; multiplet at 8~07 ppm).
When applying the process of thi.s example of
European Patent Application 23,392, using pyridine as an
acid acceptor, -the yield was only 25%.
_ 9 _
mab/~
