PROCESS FOR PRODUCING SUBSTITUTED ASYMMETRIC UREAS

Abstract: A process is disclosed for producing substituted asym­ metric ureas, starting from dialkylcarbonates, aromatic amines and aliphatic amines, by a two-step procedure and in the presence of a catalyst selected from among the Lewis' acids and the alkoxides or the hydroxides of alkali metals or alkaline earth metals.

Description: PROCESS FOR PRODUCING SUBSTITUTED ASYMMETRIC UREAS. This invention relates to a process for preparing substitute-d asymmetric ureas, which are especially useful as active ingredients in the formulation of pesticides and, more particularly, of weed-killers. The methods which are conventionally known for the preparation of asymmetric ureas are mainly based on the reaction between an aromatic isocyanate, or a carbamoyl chloride, and an aliphatic amine such as described, for example, by M.Sitting, in "Pesticides Manual Encyclopedia", 1979 Edition. This productive mode, however, involves a few problems, the most prominent of which is the toxicity of the compounds to be used, Special care and expedients of a technical nature must be adopted in shipping, storage and handling of the reactants, such as carbamoyl chlorides and isocyanates. This fact is still'more significant if one takes into account the circumstance that both the isocyanates and the carbamoyl chlorides are synthesized, in their turn, by reacting an aromatic amine with phosgene, so that their production involves additicnal hazards and considerable environmental and oecological problems. The compounds to be employed have a toxicological limit of tolerability (TLV= Threshold limiting value) which is extremely low so that the safety problems become a predominant factor when erecting industrial installations. It is required, moreover, that the saline effluents be disposed of without neglecting the pollution problems. It has now been found that it is possible to prepare substituted asymmetric ureas by reacting a dialkyl carbonate with an aromatic amine and an aliphatic amine by a simplified stepwise procedure, which requires but a minimal handling of intermediates. In addition, the use of a dialkylcarbonates solves the safety problems because they are inert towards the biological systems and are conducive to co-products (alcohols) which are nonpclluting and which can be reused. In the art the preparation of asymmetric ureas starting from aliphatic amines and from carbamates is known, special catalysts being present, as disclosed in the European Patent Application No. 82200632.6 filed on May 24, 1982. It is also known the preparation of carbamates starting from dialkyl carbonates and from aromatic amines, appropriate catalysts being present, as disclosed in the US Patens 4,268,683 and 4,268,684. These patents, however, do not teach the preparation of asymmetric ureas starting from a dialkylcarbonate and an aromatic and an aliphatic amine, by a stepwise process, which requires but a minimum handling of the intermediates and which is carried out with a single reaction catalyst being present. More particularly, according to the present invention, a substituted asymmetric urea is prepared, having the general formula: EMI3.1 wherein R1 is an aryl radical, especially phenyl, optionally carrying one or- more substituents on the ring, R2 is a straight-line or a branched alkyl radical having from 1 to 10 carbon atoms, or a cycloalkyl radical having 5 or 6 carbon atoms, R3is H or has the same meaning as R2, by a prccess characterized in that in a first reaction stage a dialkylcarbonate having the formula EMI3.2 wherein R is an alkyl radical having from 1 to 4 carbon atoms, is contacted with an aromatic amine having the formula R1NH2 wherein R1 has the same meaning as explained above, the working reaction conditions being such that the molar ratio of the dialkylcarbonate to the aromatic amine is equal to, or higher than 1 : 1, a partial conversion of the reactants taking place, the unreacted dialkylcarbonate and the co-produced alcohol being distilled off from the reaction mixture thus obtained, in a second reaction stage the residue of said distillation is contacted with an aliphatic amine having the formula: R 2R3 NH wherein R2 and R3 have the same meaning as explained above, the reaction conditions being such that the molar ratio of the aliphatic amine to the dialkylcarbonate which has been interacted in said first reaction stage is equal to or higher than 1: :1, the corresponding substituted asymmetric urea being obtained, and, moreover, said first and said second reaction stage being carried out at a temperature of from 700C to 1600C in the presence of catalytic amounts of a compound which is a member selected from the group consisting of the Lewis acids,and the alkoxides or hydroxides of alkali metals o alkaline earth metals or of zinc, whereafter the asymmetric urea is separated from the reaction mixture as obtained in the second reaction stage. Dialkylcarbonates which are usable to the ends of the present invention are dimethylcarbonate, dietthylcarbonate, dipropylcarbonate, diisopropylcarbonate and dibutylcarbonate. Examples of amines R1NH2 which can be used for the intended purpose are: aniline, 3,4-bichloroaniline, 3-chloro -4-methyl aniline, 3-chloroaniline, 4-chloroaniline and trifluoromethylaniline. Examples of amines R2R3NH which can be used to the intended purpose are: dimethylamine, diethylamine, di-nor.propylamine, di-nor.butylamine, nor.butylmethylamine, cyclohexylamine, methylamine, ethylamine, propyl- amine and butylamine. The catalysts which are useful for the purpose intended herein are members selected from the group consisting of the Lewis' acids, the alkoxides or the hydroxides of alkali metal, alkaline earth metals, or of zinc. Examples of these are: sodium methoxide, sodium ethoxide, lithium methoxide, lithium ethoxide, zinc methoxide, zinc ethoxide, zinc acetate, zinc chloride and tin chloride. The first reaction stage is carried out by contacting the dialkylcarbonate concerned with the aromatic amine, in a molar ratio of the one to the other equal to, or higher than 1 : 1, at a temperature of from 700C to 160or, in the presence of an amount of catalyst which is from 1 to 10 mol per 100 mols of the aromatic amine, until the reactants are but partially converted. It has been ascertained, in practice, that final reaction products having the expected purity are obtained if the conversion of the aromatic amine is stopped to a value not exceeding 95%. The lower limit of the conversion of the aromatic amine has no criticality but, for economical reasons, it is preferred not to fall below about 50%. The working conditions which are preferred for the first reaction stage are as follows: molar ratio of the dialkylcarbonate to the aromatic amine over 1 : 1 up to 5 : 1, temperature from 1200C to 1600C, catalyst from 5 to 10 mol per 100 mol of amine in the case of using, as catalysts, alkoxides, oxides or hydroxides, and from 1 to 5 mol of catalyst per 100 mol of amine when using the Lewis' acids as the catalysts, the amine conversion rating being from 50% to 90%. The times which are required to bring about these conversions generally vary from 1-to 6 hours. From the reaction mixture as obtained in the first reaction stage, the unreacted dialkylcarbonate and the co-produced alcohol are removed by distilling them off under an atmospheric pressure or a reduced pressure. The unreacted aromatic amine is not removed at this stage of the reaction, since it is more favorable to effect its separation from the mixture which is discharged on completion of the second reaction stage. It has been ascertained, in fact, that is said second stage the reaction runs in a quick and selective way in the presence of the aromatic amine. More particularly, during progress of said second stage, the distillation residue comes into contact with the aliphatic gamine with a molar ratio of the aliphatic amine to the dialkylcarbonate which had been interacted in the first stage equal to or higher than 1 : 1, at a temperature of from 700C to 1600C, in the presence of the catalyst charged in the first stage, the corresponding substituted asymmetric urea being thus obtained. The conditions which are preferred for the second reaction stage are as follows: molar ratio of the aliphatic amine to the dialkylcarbonate which had been interacted in the first stage higher than 1 : 1 up to 5 : 1, and temperatures from 1200C to 1400C. The times which are required for completing the reaction in the second stage vary from 1 to 3 hours as a rule. In both stage, it is also possible to work within a solvent, such as toluene, xylene, hexane, dodecylbenzene, decahydronaphthalene, tetrahydronaphthalene, diethyl ether and methyltert.butyl ether. The substituted asymmetric urea thus obtained can be withdrawn from the reaction mixture with conventional procedures such as precipitation or by distilling off the unreacted reactants, the co-produced alcohol and the solvent which may have been added to the system. The substituted asymmetric urea thus prepared can finally be subjected to purification, for example by crystallization from a solvent. The experimental examples reported hereinafter are illustrative and do not limit the scope of the invention. EXAMPLE 1 A stainless-steel autoclave is used, having a volume of 150 mls, and equipped with a jacket and a termocouple, a magnetic stirrer and a thermostatically controlled fractionation column connected to a condenser. The autoclave is charged with 7.76 g (0.083 mol) of aniline, 11.8 g (0.10 mol) of DEC (diethylcarbonate) and 0.68 g (0.01 mol) of sodium ethoxide and the reaction is carried out during 5 hours at 1200C. The pressure within the 2 autoclave attains 2 Kg/cni At the end of the period of time aforesaid, the residual DEC and the ethanol (by-product) are distilled off under a pressure lower than the ambient pressure. The residue of the distillation is supplemented with 50 g of toluene and 13 g (0.10 mol) of di-norbutylamine.The reaction is now carried out for 3 hours at 1200C and ethanol is distilled off as it is being formed. At the end of the period of time aforementioned the unreacted toluene, dibutylamine and aniline are distilled off, under a pressure which is lower than the ambient pressure and the residue is recovered. A conversion of aniline is determined, which is 62.5 molar % with a yield of useful reaction product, which is 1dibutyl-3-phenylurea, equal to 60.3% (assessed after recrystallization from nor.hexane) whereas N-ethylethylcarbanylate is obtained with a yield of 2%. EXAMPLE 2 The reactor of'Example 1 is charged with 7.76 g (0.083 mol) of aniline, 11.8 g (0.10 mol) of DEC and 0.068 g of sodium ethoxide and the reaction is caused to proceed during 5 hours at 1200C. At the end of this period of time, the unreacted DEC and the ethanol which has been formed are distilled off under a pressure lower than the ambient pressure and to the residue there are added 60 g of toluene and 8.3 g (0.085 mol) of cyclohexylamine. The reaction is carried out during 2.5 hours at 1200C while ethanol is distilled off as it is being formed. At the end of the period of time in question, toluene, cyclohexylamine and aniline which did not react are distilled off working under a pressure lower than the ambient pressure, and the residue is recovered. A conversion of aniline is determined, which is 63.5 molar %, with a yield of the useful reaction product, which is 1-cyclchexyl-3-phenylurea, equal to 58.9% (assessed upon recrystallization), whereas the yield of N-ethyl-ethylcarbanylate is 1.9%. EXAMPLE 3 The reactor of Example 1 is charged with 12.20 g (0.086 mol) of 3-chloro-4-methylaniline, 12.25 g (0.10 mol) of DEC and 0.7 g (0.01 mol) sodium ethoxide. The reaction is carried out for 5 hours at 1200C and at the end of this period of time the unreacted DEC and the by-product, ethanol, are distillled off working under a pressure which is lower than the ambient pressure. To the residue there are added 10.4 g (0.10 mol) of di.nor.propylamine and 50 g of toluene. The reaction is carried out again for 3 hours at 1150C and ethanol is distilled off as it is being produced. On completion of the reaction there is determined a conversion of the 3-chloro4-methylaniline which is equal to 64 molar %, with a yield of the useful product, 1-(3-chloro-4-methylphenyl) -3-dipropylurea equal to 61.1 % and with a yield of 2.1% for the N-ethyl-ethyl-carbanylate of the 3-chloro-4methylaniline. EXAMPLE 4 A 500-ml stainless steel autoclave-is used, which is equipped with magnetic stirrer, heating jacket thermocouple and a thermostatically controlled fractionation column which is connected to a condenser.The autoclave is charged with 64.8 g (0.40 mol of 3,4-dichloroaniline, 56.64 g (0.48 mol) of DEC and 15.1 mls of a 18% solution of sodium ethoxide (the solution is in terms of weight/ volume and the quantity used corresponds to 0.04 mol of sodium ethoxide).The reaction is carried out for 5 hours at 1200C and in the reactor the pressure attains a maxi 2 mum value of 2 Kg/cm . At the end of that period of time, the residual DEC and the as-formed ethanol are distilled off under a pressure lower than the ambient pressure. To the residue there are added 40 mls of decahydronaphthalene and 44.7 g (0.99 mol) of dimethylamine. The reaction is allowed to proceed during 3 hours at 1200C, and a maximum pressure of about 5 Kg/cm2 is attained within the reactor. At the end of this period of time, the unreacted dimethylamine is vented off the reactor ceiling and the reaction mixture is transferred into a filtration device wherein the solids are separated from the solvent and from the unreacted amine. The recovered solid is white and crystalline and has a melting point of 1520C - 1530C. The IR spectra, mass spectra and NMR spectra confirm that the compound is 3-(3,4-bichlorophenyl)-l,l-dimethylurea. In addition, a conversion of dichloroaniline is detected, which is equal to 53.1 molar %, with a yield of 50.1% of the useful reaction product (assessed upon recrystallization) and with a yield of 1.5% of N-ethyl-ethylcarbanylate of the 3,4-dichloroaniline, EXAMPLE 5 The reactor of Example 1 is charged with 17.4 g (0.11 mol) of 3,4-dichloroaniline, 50 g (0.55 mol) of DMC (dimethylcarbonate) and 0.64 g (0.005 mol) of zinc dimethoxide and the reaction is carried out with stirring for 6 hours at 1400C, a maximum pressure being attained, 2 which is about 10 Kg/cm . At the end of said period of time, the unreacted DMC and the as-formed methanol are distilled off working under a pressure which is slightly below the ambient pressure. To the residue of the distillation there are added 40 mls of xylene and 14 g (0.31 mol) of dimethylamine and the reaction is carried out for 3 hours at 1200C. At the end of said period of time the unreacted dimethylamine is evaporated off and the reaction mixture is filtered. The solid which is thus separated is dried and is identified by analysis as 3-(3,4-bichlorophenyl)-1,1 dimethylurea. The GLC-analysis (gas-liquid chromatography) of the liquid filtrate has permitted to determine a conversion of 3,4-dichloroaniline as high as 63 molar %, with a yield of the useful product of the reaction equal to 55% (evaluated upon recrystallization).As a by-product of the reaction, N-methyl-3,4-dichloroaniline is obtained with a yield of 2%. EXAMPLE 6 The reactor of Example 1 is charged with 32.4 g (0.20 mol) of 3,4-dichloroaniline, 90 g (1.0 mol) of DMC and 1.90 g (0.01 mol) of zinc acetate. The reaction is conducted at 1400C for 6 hours and a maximum pressure 2 of 9 Kg/cm is attained. At the end of this period of time, the unreacted DMC and the as-formed methanol are distilled off while working under a pressure slightly below the ambient pressure. To the residue there are added 32.9 g (0.73 mol) of dimethylamine and the reaction is carried out at 1200C for 3 hours, a maximum pressure of 2 about 11 Kg/cm2 being attained. At the end of that period of time, the unreacted dimethylamine is evaporated off and the reaction mixture is filtered. A crystalline solid is recovered, which melts at 1510C - 1520C and is analytically identified as 3-(3,4-bichlorophenyl)-1,1dimethylurea. A conversion of the dichloroaniline is experienced, which is equal to 80 molar % with a yield of 76% of the useful reaction product (evaluated upon recrystallization) and with a yield of 0.5X of N-methyldichloroaniline. EXAMPLE 7 The reactor of Example 1 is charged with 32.4 g (0.20 mol) of 3,4-bichloroaniline, 21.6 g (0.24 mol) of DMC and 1.9 g (0.015 mol) of zinc carbonate. The reaction is conducted for 6 hours at 1400C and, at the end of this period of time, the unreacted DMC and the as-formed methanol are distilled off, working under a pressure which is slightly below the ambient pressure. To the residue there are added 35 mls of toluene and 28.8 g (0.64 mol) of dimethylamine and the reaction is carried out for 3 hours at 1200C, a maximum pressure of about 12 Kg/cm being attained. At the end of that period of time, the reaction mixture is filtered and there are recovered 22.35 g of a solid product which melts at 1500C-1520C and which is identified analytically as being3-(3,4bichlorophenyl)-1,1-dimethylurea. A conversion of 3,4bichloroaniline is experienced, which is as high as 54 molar %, with a yield of 48.2 % of the useful reaction product, evaluated after recrystallization and with a yield of 0.5% of N-methyl-3,4-bichloroaniline. EXAMPLE 8 The reactor of Example 1 is charged with 9.88 g (0.1062 mol) of aniline, 50 g (0.5556 mol) of DMC and 0.92 g (0.005 mol) of zinc acetate. The reaction is carried out with stirring and under a nitrogen blanket at 140at for 6 hours. At the end of that period of time, the reactor is fed with 10 mls of dodecylbenzene, whereafter both the residual DMC and the newly formed methanol are distilled off, working under a pressure which is slightly below the ambient pressure. To the residue there are added 15.3 g (0.33 mol) of dimethylamine and the reaction is carried out for 3 hours at 1200C. At the end of such period of time, the unreacted dimethylamine is evaporated off and the reaction mixture is filetered. The solid collected on the filter is washed with 20 mls of ethyl ether and dried. There are thus recovered 13.28 g (0.081 mol) of a solid product, which melts at 1310C - 1330C and is identified by NMR and MS analyses as 3-phenyl-1,1-dimethylurea. A conversion of aniline is experienced which is as high as 78 molar %, with a yield of the useful reaction product as high as 76.2% and a yield of 0.6 % of N-methylaniline. EXAMPLE 9 The reactor of Example 1 is charged with 32.4 g (0.20 mol) of 3,4-dichloroaniline, 90.0 g (1.0 mol) of DMC and 1.9 g (0.01 mol) of zinc acetate. The reaction is carried out with stirring and under a nitrogen blanket for 6 hours at 1400C. At the end of that period of time, the unreacted DMC and the as-formed methanol are distilled off under a pressure slightly below the atmospheric pressure. To the residue there are added 30 mls of toluene and 55.8 g (0.64 mol) of N-butylmethylamine and the reaction is carried out for 3 hours at 12doC. At the end of that period of time the unreacted N-butylmethylamine is distilled off and the reaction mixture is filtered. A white crystalline solid is recovered, which melts at 990C - 1010C and is identified as N-butyl-N'-(3,4-dichlorophenyl)-N-methylurea. A conversion of the 3,4-dichloroaniline as high as 78 molar % is experienced, with a yield of 74% of the useful reaction product and with a yield of 1% in terms of N-methyldichloroaniline. EXAMPLE 10 The reactor of Example 4 is charged with 64.8 g (0.40 mol) of 3,4-dichloroaniline, 72.1 g (0.80 mol) of DMC and 3.8 g (0.02 mol) of zinc acetate. The reaction is carried out at 1400C for 6 hours. At the end of that period of time the unreacted DMC and the newly formed methanol are distilled off under a pressure.below the ambient pressure. To the residue there are added 62.3 g (1.38 mol) of dimethylamine and 60 mls of xylene and the reaction is conducted for 3 hours at 1200C. At the end of that period the unreacted dimethylamine is evaporated off and the residue is filtered. The solid collected on the filter is washed with nor.hexane and there are recovered 63.2 g of a product which has been identified as 3-(3,4-dichlorophenyl)-1 , 1-dimethylurea. A conversion of 3,4-dichloroaniline as high as 71.5 molar% is experienced, with a yield of 68.1 % of the useful reaction product (evaluated upon recrystallization) and with a yield of 1 % in terms of N-methyl-3,4-dichloroaniline.

Claims: CLAIMS 1. A process for preparing a substituted asymmetric urea having the general formula: EMI16.1 wherein R1 is an aryl radical, especially phenyl, optionally carrying one or more substituents on the ring, R2 is a straight-line or a branched alkyl radical having from 1 to 10 carbon atoms, or a cycloalkyl radical having 5 or 6 carbon atoms, R3 is H or has the same meaning as R2, by a process characterized in that: in a first reaction stage a dialkylcarbonate having the formula EMI16.2 wherein R is an alkyl radical having from 1 to 4 carbon atoms, is contacted with an aromatic amine having the formula R1NH2 wherein R1 has the same meaning as explained above, the working reaction conditions being such that the molar ratio of the dialkylcarbonate to the aromatic amine is equal to, or higher than 1:1, a partial conversion of the reactants taking place, the unreacted dialkylcarbonate and the co-produced alcohol being distilled off from the reaction mixture thus obtained, in a second reaction stage the residue of said distillation is contacted with an aliphatic amine having the formula: : R2R3NH wherein R2 and R3 have the same meaning as explained above, the reaction conditions being such that the molar ratio of the aliphatic amine to the dialkylcarbonate which has been interacted in said first reaction stage is equal to or higher than 1:1, the corresponding substituted asymmetric urea being obtained, and, moreover, said first and said second reaction stage being carried out at a temperature of from 700C to 1600C in the presence of catalytic amounts of a compound which is a member selected from the group consisting of the Lewis1 acids, and the aikoxides or hydroxides of alkali metals or alkaline earth metals or of zinc, whereafter the asymmetric urea is separated from the reaction mixture as obtained in the second reaction stage. 2. Process according to Claim 1, characterized in that the aromatic amines are members selected from the group consisting of: aniline, 3,4-bichloroaniline, 3-chloro-4-methyl aniline, 3-chloroaniline, 4-chloro aniline and trifluoromethylaniline. 3. Process according to Claim 1, characterized in that the aliphatic amines are members selected from the group consisting of: dimethylamine, diethylamine, di nor. propylamine, di-nor.butylamine, nor.butylmethylamine, cyclohexylamine, methylamine, ethylamine, propylamine and butylamine. 4. Process according to Claim 1, characterized in that the catalysts are members selected from the group consisting of: sodium methoxide, sodium ethoxide, lithium methoxide, lithium ethoxide, zinc methoxide, zinc ethoxide, zinc acetate, zinc chloride and tin chloride. 5. Process according to Claim 1, characterized in that in the first and the second stage a quantity of catalyst is used which is from 1 to 10 mols per 100 mols of the aromatic amine charged in the first stage. 6. Process according to Claim 1, characterized in that in the first reaction stage a quantity of aromatic amine is converted which is from 50% to 95%. 7. Process according to Claim 1, characterized in that the first stage is carried out with a molar ratio of the dialkylcarbonate to the aromatic amine which is higher than 1:1 and up to 5:1 at a temperature of from 1200C to 1600C with from 5 to 10 mols of catalyst per 100 mols of aromatic amine in the case of alkoxides, oxides or hydroxides and with from 1 to 5 mols of catalyst per 100 mols of amine in the case of Lewis' acids, for times from 1 to 6 hours and with conversion of the dialkylcarbonate from 50% to 90%. 8. Process according to Claim 1, characterized in that in the second reaction stage the molar ratio of the aliphatic amine to the dialkylcarbonate interacted in the first stage is adopted higher than 1:1 and up to 5:1, at a temperature of from 1200C to 1400C, with the catalyst fed to the first stage and for a time from 1 to 3 hours.

Inventors: FORNASARI, GIANCARLO, ROMANO, UGO, SGAMBATO, UMBERTO
Applicants: ANIC S.P.A.
Application year: 1983
Main classification: C07C127
IPC codes: A01N47, C07C273, C07C67, C07C275, C07C239