Aminophenyl ketone derivatives and a method for the preparation thereof

Abstract: The present invention provides o -aminophenyl ketone derivatives which are intermediates useful in the manufacture of herbicidal sulfamoyl urea compounds, including the crop selective herbicide 1-{[ o -(cyclopropylcarbonyl)phenyl]-sulfamoyl}-3-(4,6-dimethoxy-2-pyrimidinyl)urea. Also provided is a method for the preparation of said intermediates.

Description: The present invention provides o-aminophenyl ketone derivatives of formula I wherein R, R 1 and X are as defined below. Compounds of formula I are useful as intermediates in the manufacture of a wide variety of herbicidal sulfamoyl urea derivatives, and in particular, the manufacture of the crop-selective herbicidal agent 1-{[ o -(cyclopropyl-carbonyl)phenyl]sulfamoyl}-3-(4,6-dimethoxy-2-pyrimidinyl)urea. Also provided is a method for the preparation of said formula I intermediate. The invention provides a compound of formula I wherein R is straight or branched C 1 -C 6 alkyl or phenyl optionally substituted with one or more substituents the same or different selected from C 1 -C 3 alkyl, C 1 -C 3 alkoxy, chlorine and bromine; R 1 is hydrogen, cyano, nitro, halogen, formyl, C 1 -C 4 alkyl optionally substituted with one or more substituents the same or different selected from halogen, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3- alkylsulfinyl and C 1 -C 3 alkylsulfonyl, C 1 -C 4 alkoxy optionally substituted with one or more substituents the same or different selected from halogen, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3- alkylsufinyl and C 1 -C 3 alkylsulfonyl, C 1 -C 4 alkylthio optionally substituted with one or more substituents the same or different selected from halogen, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3- alkylsufinyl and C 1 -C 3 alkylsulfonyl, C 1 -C 4 alkylsulfinyl optionally substituted with one or more substituents the same or different selected from halogen, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3- alkylsufinyl and C 1 -C 3 alkylsulfonyl, C 1 -C 4 alkylsulfonyl optionally substituted with one or more substituents the same or different selected from halogen, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3- alkylsufinyl and C 1 -C 3 alkylsulfonyl, C 1 -C 4 alkylcarbonyl optionally substituted with one or more substituents the same or different selected from halogen, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3- alkylsufinyl and C 1 -C 3 alkylsulfonyl, C 1 -C 4 alkoxycarbonyl optionally substituted with one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, di(C 1 -C 4 alkyl)amino optionally substituted with one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, di(C 1 -C 4 alkyl)aminocarbonyl optionally substituted with one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, di(C 1 -C 4 alkyl)aminosulfonyl optionally substituted with one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, or a heterocyclic ring having 2 to 6 carbon atoms and 1 to 3 heteroatoms the same or different selected from nitrogen, oxygen and sulfur atoms and being optionally substituted on the carbon atoms with one or more substituents the same or different selected from halogen, C 1 -C 4 alkyl and C 1 C 4 haloalkyl; X is -(CH 2 ) 3 -Y, cyclopropyl or tetrahydro-2-oxo-3-furyl; and Y is chlorine, bromine or hydroxy; or an acid addition salt thereof. The invention also provides a process for preparing a compound of formula A wherein R 1 is as defined in claim 1 which comprises the following steps: i) reacting a compound of formula B wherein R and R 1 are as defined in claim 1 with a compound of formula C in the presence of a base and an organic solvent to form a compound of formula E and optionally hydrolysing any compound of formula D present to give a compound of formula E; if desired isolating compound E by crystallization; ii) reacting compound E with concentrated HCl or HBr in the presence of an organic solvent optionally in the presence of water to form a compound of formula F; wherein Y 1 is Cl, Br or OH iii) treating compound F with an aqueous base at an elevated temperature to give a compound of formula G; iv) treating compound G with a strong acid to give a compound of formula H; and and v) reacting compound H with HCl to form the compound of formula A. Compound A wherein R 1 is hydrogen, 1-( o -aminophenyl)-4-chloro-1-butanone hydrochloride, is used in the manufacture of the herbicidal intermediate o -(aminophenyl)cyclopropyl ketone. A description of o -(aminophenyl)cyclopropyl ketone and its use in the manufacture of 1-{[ o -(cyclopropylcarbonyl)phenyl]-sulfamoyl}-3-(4,6-dimethoxy-2-pyrimidinyl)urea herbicide is described in EP-A-0 463 287. The present invention also avoids the use of o -nitrobenzoyl chloride, which is an explosive, as an intermediate. The base used in step (i) may be a magnesium C 1 -C 4 alkoxide, preferably one which is readily available such as magnesium methoxide or magnesium ethoxide. The organic solvent used in step (i) may be an aromatic hydrocarbon or dialkyl ether such as toluene, xylene or tetrahydrofuran. The organic solvent used in step (ii) for preparing compound F may be an inert organic solvent such as toluene or xylene and the acid used in step (ii) may be a mineral acid such as concentrated HCl. When water is present compound of formula F wherein Y 1 is OH may be formed. The base used in step (iii) for preparing compound G may be an alkali metal hydroxide such as sodium hydroxide or potassium hydroxide. The elevated temperature in step (iii) may be any temperature in excess of 25 °C, preferably about 90 °-130 °C. The strong acid used in step (iv) for preparing compound H may be sulfuric acid. The acid used for preparing compound A in step (v) may be a mineral acid such as concentrated HCl. The compounds of the invention may be used to prepare herbicidal sulfamoyl urea compounds (K) by employing the process of the invention to prepare compounds of formula A and converting said formula A compounds to the corresponding o -(aminophenyl)cyclopropyl ketones (J) using conventional methods described in EP-A-0 655 436 and converting said phenyl ketones to the desired sulfamoylurea herbicidal products, preferably the cereal-selective, herbicidal sulfamoyl urea, 1-{( o -(cyclopropylcarbonyl)phenyl]sulfamoyl}-3-(4,6-dimethoxy-2-pyrimidinyl urea. The conversion of the phenyl ketone derivatives to sulfamoylurea herbicides may be accomplished by known processes. The preparation is shown in flow diagram I. In accordance with the process of the invention, the compound of formula A is prepared as described hereinabove and converted to the o -(aminophenyl)cyclopropyl ketone compound of formula J by conventional dehydrohalogenation techniques and the formula J compound may be reacted with a 2-aminoaryl compound of formula L and chlorosulfonyl isocyanate in the presence of triethylamine and a solvent to give the desired herbicidal sulfamoyl urea of formula K. The invention is further illustrated in the examples, below, but is not to be deemed limited thereby. The terms NMR and MS designate proton nuclear magnetic resonance and mass spectrometry, respectively. EXAMPLE 1 Preparation of 2'-(Tetrahydro-2-oxo-3-furoyl)-p-toluenesulfonanilide To a mixture of 40 mL of toluene and 2.03 g (178 mmol) of magnesium ethoxide in a flask under nitrogen at 5-10° C is charged 4.6 g (36 mmol) of 2-acetylbutyrolactone over 2 minutes. The resulting slurry is stirred for 10 minutes at 5-10°C and for about 1.5 hours at 20°C. The reaction mixture is treated with a solution of 10.0 g (32 mmol) of N-p-tolylsulfonyl anthranoyl chloride in 20 mL of toluene, stirred several hours at ambient temperature and for about 2 hours at 45-50°C. Water (120 mL) is added and the gray slurry is stirred for about 4 hours at 65-70°C. The pH is adjusted to 1 with concentrated sulfuric acid. The phases are separated and the organic layer is filtered to afford 7.6 g of 2'-(tetrahydro-2-oxo-3-furoyl)- p -toluenesulfonanilide. The remaining product is isolated from the organic layer filtrate by concentration in vacuo to give an additional 2.1 g of product for an overall yield of 83% (mp 138-141° C). The product is identified by NMR and MS analyses. EXAMPLE 2 Preparation of 2'-(Cyclopropylcarbonyl)-p-toluenesulfonanilide A two phase slurry mixture of 3.56 g (1.0 mmol) of the product from example 1, 25 mL of toluene and 20 mL of 37% HCl is refluxed for about 12 hours, cooled and the resulting slurry is filtered to afford 1.98 g of 4-chloro-1-(2-N-tosylaminophenyl)-1-butanone. The filtrate phases are separated and the aqueous phase is extracted with toluene. The organic phases are combined and concentrated in vacuo to give the remaining 4-chloro-1-(2-N-tosylaminophenyl)-1-butanone product (1.15 g) for an overall yield of 90% (mp 108-113 °C). The product is identified by NMR and MS analyses. To a solution of 1.62 g (4.6 mmol) of 4-chloro-1-(2-N-tosylaminophenyl)-1-butanone in 10 mL of toluene is charged 17.3 g (28.7 mmol) of 6.6% sodium hydroxide solution. The resulting two phase mixture is refluxed for about 1 hour, cooled and adjusted to pH 1 with concentrated sulfuric acid. The organic layer is separated and concentrated in vacuo to afford 1.50 g of 2'-(cyclopropylcarbonyl)- p -toluenesulfonanilide in 100% yield (mp 92-100 °C). The product is identified by NMR and MS analyses. EXAMPLE 3 Preparation of 1-(o-Aminophenyl)-4-chloro-1-butanone hydrochloride The product of example 2 (1.5 g, 4.7 mmol) is treated with 96% sulfuric acid and heated to 90 °C for 15 minutes. The solution is cooled, adjusted to pH 9 with ammonium hydroxide and extracted with methylene chloride. The combined extracts are concentrated in vacuo to provide 1-( o -aminophenyl)-4-hydroxy-1-butanone ( 80% yield, mp 58-61 °C). The product is identified by NMR and MS analyses. A mixture of 9.3 g (5.1 mmol) of 1-( o -aminophenyl)-4-hydroxy-1-butanone, 26 mL of water and 90 mL of 37% HCl is refluxed for about 6.5 hours, cooled and filtered to afford 8.0 g of 1-( o -aminophenyl)-4-chloro-1-butanone hydrochloride. Extraction of the aqueous mother liquor with methylene chloride gives an additional 1.10 g of the title product for an overall yield of 73% (mp 142-145 °C). The product is identified by NMR and MS analyses. EXAMPLE 4 Preparation of o-Aminophenyl cyclopropyl ketone A solution of 0.30 g (1.3 mmol) of 1-( o -aminophenyl)-4-chloro-1-butanone hydrochloride in 3 mL of methylene chloride and 3 mL of ethylene dichloride is treated with 1.2 g (3 mmol) of 10% sodium hydroxide solution and 0.05 g (0.2 mmol) of 75% aqueous methyl tributylammonium chloride and heated to 50 °C for about 5 hours. After cooling to room temperature, the phases are separated. The aqueous layer is extracted with methylene chloride. The combined organic extracts are washed with water and concentrated in vacuo to give 0.14 g (70% yield) of o -aminophenyl cyclopropyl ketone (mp 46-48 °C). The product is identified by NMR and MS analyses.

Claims: A compound of the formula wherein Rx is straight or branched C 1 -C 6 alkyl or phenyl optionally substituted with one or more substituents the same or different selected from C 1 -C 3 alkyl, C 1 -C 3 alkoxy, chlorine and bromine; R 1 is hydrogen, cyano, nitro, halogen, formyl, C 1 -C 4 alkyl optionally substituted with one or more substituents the same or different selected from halogen, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3 -alkylsulfinyl and C 1 -C 3 alkylsulfonyl, C 1 -C 4 alkoxy optionally substituted with one or more substituents the same or different selected from halogen, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3 -alkylsufinyl and C 1 -C 3 alkylsulfonyl, C 1 -C 4 alkylthio optionally substituted with one or more substituents the same or different selected from halogen, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3- alkylsufinyl and C 1 -C 3 alkylsulfonyl, C 1 -C 4 alkylsulfinyl optionally substituted with one or more substituents the same or different selected from halogen, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3- alkylsufinyl and C 1 -C 3 alkylsulfonyl, C 1 -C 4 alkylsulfonyl optionally substituted with one or more substituents the same or different selected from halogen, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3- alkylsufinyl and C 1 -C 3 alkylsulfonyl, C 1 -C 4 alkylcarbonyl optionally substituted with one or more substituents the same or different selected from halogen, C 1 -C 3 alkoxy, C 1 -C 3 alkylthio, C 1 -C 3- alkylsufinyl and C 1 -C 3 alkylsulfonyl, C 1 -C 4 alkoxycarbonyl optionally substituted by one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, di(C 1 -C 4 alkyl)amino optionally substituted by one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, di(C 1 -C 4 alkyl)aminocarbonyl optionally substituted by one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, di(C 1 -C 4 alkyl)aminosulfonyl optionally substituted by one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, or a heterocyclic ring having 2 to 6 carbon atoms and 1 to 3 heteroatoms the same or different selected from nitrogen, oxygen and sulfur atoms and being optionally substituted on the carbon atoms with one or more substitutents the same or different selected from halogen, C 1 -C 4 alkyl and C 1 -C 4 haloalkyl; X is -(CH 2 ) 3 -Y, cyclopropyl or tetrahydro-2-oxo-3-furyl; and Y is chlorine, bromine or hydroxy; or an acid addition salt thereof. The compound according to claim 1 wherein R 1 is hydrogen and optionally R is methyl or p -tolyl. The compound according to claim 1 or claim 2 wherein X is cyclopropyl, -(CH 2 ) 3 -Cl, or tetrahydro-2-oxo-3-furyl. A process for preparing a compound of formula A characterized by : i) reacting a compound of formula B with a compound of formula C in the presence of a base and an organic solvent to form a compound of formula E and optionally hydrolysing any compound of formula D present to give a compound of formula E; ii) reacting compound E with concentrated HCl or HBr in the presence of an organic solvent optionally in the presence of water to form a compound of formula F where Y 1 = Cl, Br or OH iii) treating compound F with an aqueous base at an elevated temperature to give a compound of formula G iv) treating compound G with a strong acid to give a compound of formula H and v) reacting compound H with HCl to form the compound of formula A; in which formulae R and R 1 are as defined in claim 1. The process according to claim 4 wherein the base in step (i) is magnesium ethoxide and the organic solvent is toluene; the organic solvent in step ii) is toluene; the base in step iii) is NaOH; and the strong acid in step iv) is sulfuric acid. The process according to claim 4 or claim 5 wherein R 1 is hydrogen. The process according to any one of claims 4 to 6 wherein R is p -tolyl or methyl. The process according to any one of claims 4 to 7 which further comprises reacting the compound of formula A with a base to prepare o -aminophenyl cyclopropyl ketone. A process for preparing a sulfamoyl urea compound of formula K wherein R 1 is as defined in Claim 1; z is N or CR 3; R 2 is hydrogen, halogen, C 1 -C 4 alkyl optionally substituted with one or more substituents the same or different selected from halogen or C 1 -C 3 alkoxy, C 1 -C 4 alkoxy optionally substituted with one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, C 1 -C 4 alkylthio optionally substituted with one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, C 1 -C 4 alkylsulfinyl optionally substituted with one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, C 1 -C 4 alkylsulfonyl optionally substituted with one or more the same or different selected from halogen and C 1 -C 3 alkoxy groups, or C 1 -C 4 alkylamino or di(C 1 -C 4 alkyl)amino each alkyl group being optionally substituted with one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy; R 3 is hydrogen or halogen; and R 4 is hydrogen, C 1 -C 4 alkyl optionally substituted with one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, C 1 -C 4 alkoxy optionally substituted with one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, C 1 -C 4 alkylthio optionally substituted with one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, C 1 -C 4 alkylsulfinyl optionally substituted with one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, C 1 -C 4 alkylsulfonyl optionally substituted with one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, or C 1 -C 4 alkylamino or di(C 1 -C 4 alkyl)amino each alkyl group being optionally substituted with one or more substituents the same or different selected from halogen and C 1 -C 3 alkoxy, characterized by : i) preparing a compound of formula A by a process as claimed in Claim 4; ii) dehydrohalogenating the compound of formula A obtained by step (i) above to form the o -(aminophenyl)cyclopropyl ketone of formula J and iii) reacting said o -(aminophenyl)cyclopropyl ketone with a 2-aminoaryl compound of formula L and chlorosulfonyl isocyanate, in the presence of triethylamine and a solvent to give the desired sulfamoyl urea compound of formula K. The process according to claim 9 for preparing a compound of formula K wherein Z is CR 3 ; R 1 and R 3 are each hydrogen; and R 2 and R 4 are each methoxy.

Inventors: CORTES DAVID ANDRES, KREMER KENNETH ALFRED MARTIN, CORTES, DAVID ANDRES, KREMER, KENNETH ALFRED MARTIN, Cortés, David Andrés 
Applicants: AMERICAN CYANAMID CO, AMERICAN CYANAMID COMPANY
Application year: 1997
Main classification: C07D307
IPC codes: C07C315, C07D307, C07C225, C07C311, C07D251, A01N47, C07C49, C07C221, C07D239