|Title of Invention||
PROCESS FOR PREPARING ACYLSULFAMOYLBENZAMIDES
|Abstract||The invention relates to a process for the preparation of a compound of formula (1) which comprises reaction of a compound of formula (II) with a compound of the formula (III) in the presence of a chlorinating agent, followed by reaction of the resultant compound of the formula (IV) with a compound of formula (V) in the presence of a base wherein the various symbols are as defined in claim 1.|
Process for Preparing Acylsulfamoylbenzamides
This invention relates to the technical field of chemical processes for the preparation of compounds, particularly a novel process for the preparation of a wide range of acylsulfamoylbenzamides, which compounds are useful* e. g. as safeners for pesticides.
The use of safeners is an increasingly valuable tool for extending the practical utility of many types of pesticides, in particular herbicides, in crops of useful plants such as maize, rice, or cereals, particularly in post-emergence application.
Patent Publication Number WO 99/16744 describes acylsulfamoylbenzamide derivatives and their use as safeners for the control of weeds by herbicides. The safened herbicide mixtures possess very desirable agronomic properties and may potentially of commercial utility.
Various processes are described for the preparation of these compounds in the above publication, however these methods are not always very efficient and generally require many reaction steps from readily available starting materials. Consequently it is of value to develop a new process which does not suffer from these disadvantages and can therefore be useful for industrial scale operations.
Two general processes for preparing acylsulfamoylbenzamide derivatives are described in WO 99/16744.
The first process described involves the acylation of a sulfamoylbenzamide using a benzoic acid halide, anhydride or carbonylimidazolide, or using a benzoic acid and a coupling agent such as N,N-dicyclohexylcarbodiimide. A number of specific examples of this process are described therein, which are carried out by heating a mixture of a benzoic acid with the sulfamoylbenzamide, 1,1'-carbonyldiimidazoIe and 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) in tetrahydrofuran. However this procedure is of limited value for large scale or industrial operations because of the
moderate yields obtained, as well as the prohibitively expensive 1,1'-carbonyldiimidazole which additionally gives rise to substantial waste by-products.
The second general process described in the above reference involves the reaction of an activated acylsulfamoylbenzoic acid derivative with an amine, but this method is not specifically exemplified therein. A disadvantage of this approach is that procedures for the preparation of the activated acylsulfamoylbenzoic acid derivative, such as the acid chloride derivative, are generally inefficient since many reaction steps are involved, leading to poor or moderate overall yields.
In order to overcome the above limitations of the known processes we have now developed a new two step process for the preparation of acylsulfamoylbenzamide compounds, which involves a reduced number of reaction steps and which is applicable to industrial scale processes. "
According to the present invention there is provided a process for the preparation of a compound of general formula (I):
preferably from 1.1 to 2 molar equivalents per equivalents of (II) and (III), most preferably from 1.2 to 1.9 molar equivalents per equivalents of (II) and (III). When Y is CI, the amount of chlorinating agent used is preferably from 1 to 2 molar equivalents per equivalent of compound (II), more preferably from 1.1 to 2 molar equivalents per equivalent of (II), most preferably from 1.2 to 1.9 molar equivalents per equivalent of (II).
In reaction step a) the compound of formula (IV) can be isolated by common or customary methods, for instance preferably by partial evaporation during which it precipitates and may be filtered off.
In a further feature of the invention the unreacted excess chlorinating agent, which in the case of thionyl chloride is present in the distillate, may be recycled.
The ratio" of (II):(Illa) is preferably 1:1, but in some cases it is beneficial to add a slight excess (up to 10%) of the acid (Ilia), which has the advantage of ensuring a more complete conversion of the acid (II) in the reaction. This variation is preferably used if the corresponding acid chloride of formula (lllb) remains soluble in the reaction mixture after partial evaporation, since separation from the precipitated desired product (IV) is then effected.
A catalyst such as a N,N-diaIkylacylamide, for example N,N-dimethylformamide or N,N-dibutylformamide, or a cyclic amine such as pyridine <: quinoline is optionally also present in the reaction mixture.> The reaction can be conducted in the absence or preferat presence of a stable and inert solvent, which can be an non-polar or a polar organic solvent which essentially do not react with the chlorinating agent or the compounds (III) or V) in the reaction mixture. It is for example a non-polar organic solvent which is preferably selected from
aliphatic or aromatic hydrocarbons such as alkalies, for example heptane, octane, or an alkylated benzene such as toluene, dimethylbenzenes (xylols) or trimethylbenzenes, or paraffin oil,
halogenated aliphatic hydrocarbons such as dichloromethane, or halogenated aromatic hydrocarbons such as chlorobenzene or dichlorobenzene, or haloalkylbenzenes such as benzotrifiuoride, and
silicon oils. The most preferred solvents are chlorobenzene and toluene.
The reaction temperature in step a) may vary within wide limits dependent on the solvent and pressure used. For example, the reaction temperature is from 70°C to 140°C, preferably from 80°C to 130°C, more preferably from 80°C to 115°C.
The reaction step a) generally proceeds in excellent yield, with typical yields of the compound of formula (IV) in excess of 90% or even 95%. The purity of the compound of formula (IV) is generally very high (typically at least 95%). The acid chloride derivative of formula (II lb) above is formed as an intermediate in the preferred reaction where the compound of formula (Ilia) is used as starting material, and acylates the sulfamoyl moiety of the compound of formula (II) and/or its acid chloride derivative of formula (VI):
In contrast with the above-mentioned preparation of acyisulfamoyl benzoic acid chlorides from the corresponding benzoic acids of formula (III) via separate chlorination of the compound of formula (II), unwanted dimeric side-products are essentially avoided in the process of the invention.
The reaction of the compound of formula (IV) with the compound of formula (\/) in step b) can be performed with or without an additional base. Preferably an additional base is used in which case it may be an inorganic base such as an alkali metal hydroxide or alkoxide, for example sodium hydroxide, potassium hydroxide or sodium methoxide, or an alkali metal carbonate such as potassium carbonate, sodium carbonate or lithium carbonate, or an alkali metal bicarbonate such as sodium
bicarbonate or potassium bicarbonate, or an alkali metal alkanoate such as sodium
acetate, or an alkaline earth metal hydroxide, carbonate or bicarbonate, or an organic
base such as a trialkylamine for example triethylamine or tributylamine, or a N-
dialkylaniline such as dimethylaniline.
The preferred additional base is triethylamine, potassium carbonate or sodium
The amount of the additional base used can generally be varied within wide limits
and optimized by preliminary testing. Preferably the ratio of molar equivalents of
additional base to molar equivalents of the compound of formula (IV) is from 1.2:1 to
1:1.2, more preferably equimolar amounts of base and compound (IV).
The amount of amine (V) used is preferably a small excess in relation to the amount
of (IV), typically about 1.05 molar equivalents of (V) for 1 molar equivalent of (IV).
It is also possible to use 2 molar equivalents of the compound of formula (V) wherei n
one molar equivalent is utilised as the base in the reaction:
The process step b) is typically carried out in the presence or absence of a solvent.
When a solvent is used a wide variety of polar or non-polar solvents may be
employed, as long as they do not substantially react with the compound of formula
(IV). A number of solvents may be used, for example
aromatic hydrocarbons such as an alkylated benzene, for example toluene, or nitriles
such as cyanoalkanes for example acetonitrile, or halogenated hydrocarbons such as
haloalkanes, for example dichloromethane, or halogenated aromatic compounds
such as halobenzenes, for example chlorobenzene, or ethers such as dialkyl ethers,
for example diethyl ether or diglyme, or cyclic ethers such as tetrahydrofuran or
dioxan, or a N,N-dialkylacylamide such as N,N-dimethyIformamide or N,N-
dimethylacetamide, or a N-alkylpyrroIidinone such as N-methylpyrrolidinone.
Nitrile solvents are preferred, most particularly acetonitrile.
The reaction temperature for step b) is preferably from 0°C to 150°C, more preferably from 0°C to 60°C, most preferably from 10°C to 20°C.
The product of formula (I) can be isolated in a simple manner, for example by dilution of the reaction mixture with water, followed by acidification with, for example a mineral acid such as hydrochloric acid, and filtration.
The isolated yield of the compound of formula (I) is generally very high, typically in excess of 90% or even 95%. The product is generally obtained in high purity, typically at least 95%.
The process of the invention, depending upon the chlorinating agent may also be carried out as a one-pot procedure. In this variation, reaction step a) is preferably followed by removal (for example by evaporation) of remaining chlorinating agent, followed in the same pot by the reaction step b).
In a further feature of the invention there is provided a process for the preparation of a compound of formula (IV) as defined above, by the reaction of a compound of formula (II) as defined above, with a compound of formula (III), preferably compound (Ilia) as defined above, in the presence of a chlorinating agent as defined above (preferably thionyl chloride).
In a further feature of the invention there is provided a process for the preparation of a compound of formula (IV) as defined above, by the reaction of a compound of formula (II) as defined above, with a compound of formula (lllb) as defined above in the presence of a chlorinating agent as defined above (preferably thionyl chloride).
In a further feature of the invention there is provided a process for the preparation of a compound of formula (I) as defined above, by the reaction of a compound of formula (IV) as defined above, with a compound of formula (V) as defined above:
In the formula (I) and all the formulae hereinabove and hereinbelow, the terms mentioned have the meanings outlined below:
The term "halogen" includes fluorine, chlorine, bromine and iodine.
The term "(CrC4)-alkyl" is to be understood as a straight-chain or branched hydrocarbon radical having 1, 2,3 or 4 carbon atoms, for example the methyl, ethyl, propyl, isopropyl, 1-butyl, 2-butyl, 2-methylpropyl ortert-butyl radical.
Correspondingly, alkyl radicals having a greater range of carbon atoms are to be understood as straight-chain or branched saturated hydrocarbon radicals which contain a number of carbon atoms which corresponds to this range. The term n(CrC6)-aIkyr thus includes the abovementioned alkyl radicals, and also, for example, the pentyl, 2-methylbutyl, 1,1-dimethylpropyl and hexyl radical.
n(CrC4)-haioalkyr or n(CrC6)-haloalkyP are to be understood as an alkyl group mentioned under the term n(CrC4)-alkyl" or n(Ci-C6)-alkyln respectively in which one or more hydrogen atoms are replaced by the corresponding number of identical or different halogen atoms, preferably chlorine or fluorine, such as the trifluoromethyl, the 1-fluoroethyl, the 2,2,2-trifluoroethyl, the chloromethyl, fluoromethyl, the difluoromethyl and the 1,1,2,2-tetrafluoroethyl group.
"(CrC^-alkoxy" or n(CrC6>alkoxy" are to be understood as an alkoxy group whose hydrocarbon radical has the meaning given under the term "(CrC^alkyl" or "(Ci-C6)-alkyl" respectively. Alkoxy groups embracing a larger range of carbon atoms are to be understood likewise.
The terms "alkenyl" and "alkynyl" having a prefix stating a range of carbon atoms denote a straight-chain or branched hydrocarbon radical having a number of carbon atoms corresponding to this range, this hydrocarbon radical having at least one multiple bond which can be in any position of the unsaturated radical in question. ,,(C2-C6)-alkenyln thus denotes, for example, the vinyl, allyl, 2-methyl-2-propenyl, 2-butenyl, pentenyl, 2-methylpentenyl or the hexenyl group. "^-CeJ-alkynyl" denotes, for example, the ethinyl, propargyl, 2-methyl-2-propynyl, 2-butynyl, 2-pentynyl and the 2-hexynyl group.
n(C3-C8)-cycloalkyP denotes monocyclic alkyl radicals, such as the cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl orcyclooctyl radical and bicyclic alkyl radicals, such as the norbornyl radical.
The amounts, relative amounts, percentages or ratios refer to the weight unless another definition is specifically given.
Example 1 4-[[(2-Methoxy-5-chlorobenzoyl)amino]sulfonyl]benzoyl chloride
A mixture of 4-aminosulfonylbenzoic acid (1 mol), 2-methoxy-5-chlorobenzoic acid (1 mol) and thionyl chloride (2.5 mol) in chlorobenzene (700 ml) was heated at 120°C for 7-9 hours. After the reaction was complete 200 ml of the solvent was removed in vacuo. The mixture was cooled and the precipitate filtered off and washed with heptane to give the title compound , mp. 138-140°C, yield 93 % of theory. 4-[[(Benzoyl)amino]sulfonyl]benzoyl chloride was prepared in a similar manner from 4-aminosulfonylbenzoic acid and benzoic acid, mp. 180-182°C, yield 96 % of theory. 4-[[(2-Chlbrobenzoyl)amino]sulfonyl]benzoyl chloride was prepared in a similar manner from 4-aminosulfonylbenzoic acid and 2-chlorobenzoic acid, mp. 198-20Q°C, yield 95 % of theory.
Example 2 N,N-Diethyl-4-[[(2-methoxybenzoyl)amino]sulfonyl]benzamide
To a suspension of 4-[[(2-methoxybenzoyl)amino]sulfonyl)benzoyl chloride (1 mol) and diethylamine (1 mol) in acetonitrile (1000 ml), was added triethylamine (1 mol) at 10° C. The mixture was stirred for 2 hours at 20°C and diluted with water (500ml). The white precipitate was filtered off, washed and dried to give the title compound. The yield of product obtained was 98 % of theory, and the purity 98 %.
Example 3 N-Cyclopropyl-4-[[(2-chlorobenzoyl)amino]sulfonyl]benzamide
By employing the procedure described in Example 2 but using potassium carbonate (1 equivalent) instead of triethylamine, there was obtained the title compound in a yield of 99% of theory.
In the Tables 1 to 3 below are listed a number of examples of compounds of formula (I) which are prepared by the process of the invention.
The abbreviations in the tables 1 to 6 denote:
Bu = n-butyl Et = ethyl
Me = methyl c = cyclo
Pr = n-propyl s = secondary
i = iso Mp = melting point
t = tertiary
If an alkyl radical is listed in the tables without any further specification, this alkyl radical is straight-chain.
|Indian Patent Application Number||3499/CHENP/2005|
|PG Journal Number||24/2009|
|Date of Filing||23-Dec-2005|
|Name of Patentee||BAYER CROPSCIENCE AG|
|Applicant Address||ALFRED-NOBEL-STRASSE 50, 40789 MONHEIM,|
|PCT International Classification Number||C07C 303/40|
|PCT International Application Number||PCT/EP04/06295|
|PCT International Filing date||2004-06-11|