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GB2106499A - Method for making benzoylphenylureas - Google Patents

Method for making benzoylphenylureas Download PDF

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Publication number
GB2106499A
GB2106499A GB08128333A GB8128333A GB2106499A GB 2106499 A GB2106499 A GB 2106499A GB 08128333 A GB08128333 A GB 08128333A GB 8128333 A GB8128333 A GB 8128333A GB 2106499 A GB2106499 A GB 2106499A
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compound
formula
alkyl
above defined
individually
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GB2106499B (en
Inventor
David Philip Clifford
Robert Arthur Sewell
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Dow Chemical Co Ltd
Dow Chemical Co
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Dow Chemical Co Ltd
Dow Chemical Co
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Priority to GB08128333A priority Critical patent/GB2106499B/en
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C265/00Derivatives of isocyanic acid
    • C07C265/12Derivatives of isocyanic acid having isocyanate groups bound to carbon atoms of six-membered aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C275/00Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
    • C07C275/46Derivatives of urea, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylureas
    • C07C275/48Y being a hydrogen or a carbon atom
    • C07C275/54Y being a carbon atom of a six-membered aromatic ring, e.g. benzoylureas
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07CACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/39Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton at least one of the nitrogen atoms being part of any of the groups, X being a hetero atom, Y being any atom
    • C07C323/43Y being a hetero atom
    • C07C323/44X or Y being nitrogen atoms

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

A process for preparing a compound having the general formula: <IMAGE> wherein X and Y are individually H, F, Cl, alkyl or haloalkyl; R and R' are individually H, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro or cyano; wherein T is halogen, halogenated alkyl or the group ZR'' wherein R'' is H, alkyl, aryl, alkyl, halogenated alkyl, halogenated alkylene, pyridyl, substituted pyridyl, phenyl or substituted phenyl and Z is O or S, comprises reacting an aniline compound having the formula: <IMAGE> wherein R, R', R'' and R are as above defined with an active carbonyl compound of the formula: <IMAGE> wherein W is individually Cl, alkoxy or haloalkoxy, optionally in the presence of a tertiary base, and thereafter reacting the resulting compound of the formula: <IMAGE> wherein R, R', R'' and T are as above defined and V is NCO or <IMAGE> wherein W is as above defined with a compound having the formula: <IMAGE> wherein X and Y are as above defined, at a temperature in the range of from 80 DEG C to 180 DEG C.

Description

SPECIFICATION Method for making benzoylphenylureas This invention relates to a method for making benzoylphenylureas and, more particularly, relates to a process comprising a novel sequence of steps for preparing penzoylphenylureas.
We have now found that benzoylphenylureas can be conveniently and economically prepared by a process which comprises reacting an aniline compound with an active carbonyl compound and thereafter reacting the resulting product with a benzamide.
More specifically, the present invention comprises a process for making a compound having the formula
wherein X and Y are individually H,F,CI, alkyl or haloalkyl; R and R' are individually H, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro or cyano; wherein T is halogen, halogenated alkyl or the group ZR" wherein R" is H. alkyl aryl, alkyl, halogenated alkyl, halogenated alkylene, pyridyl, substituted pyridyl, phenyl or substituted phenyl and Z is O or S,- which comprises reacting an aniline compound having the formula:-
wherein R, R', R" and T are as above defined with an active carbonyl compound of the formula::-
wherein W is individually Cl, alkoxy or haloalkoxy, optionally in the presence of a tertiary base, and thereafter reacting the resulting compound of the formula:-
wherein R, R', R" and Tare as above defined and V is NCO or
wherein W is as above defined with a compound having the formula:-
wherein X and Y are as above defined, at a temperature in the range of from 800 to 1 800C.
When carrying out the reactions wherein the active carbonyl compound contains an alkoxy or haloalkoxy group, novel compounds are obtained.
The reactions of the active carbonyl compound with the aniline compound may be carried out at a temperature in the range of from 200 to 1 200C and are preferably carried out at ambient to reflux temperatures in the presence of an inert solvent, preferably ethyl acetate or tetrahydrofuran and an acid acceptor such as a tertiary amine or an excess of the aniline compound.
The reactions of the isocyanate compound with the benzamide compound are preferably carried out at reflux temperatures in the presence of inert solvents such as, for example, o- dichlorobenzene or xylene.
The invention is further illustrated by the following examples.
Example 1 4-(2,2-Dichloro-1 ,1 -difluoroethoxy)phenyl isocyanate A solution of 4-(2,2-dichloro-1,1 -difluoroethoxy) benzeneamine (72.6 g) in ethyl acetate (200 ml) was added to a solution of phosgene (large excess) in ethyl acetate (800 ml) with stirring. The reaction mixture was allowed to stand at 220C for 20 hours. The ethyl acetate and excess phosgene were removed by distillation at atmospheric pressure. The black residue was then distilled under high vacuum to give a clear distillate (56.0 g, 70 percent), b.p.1mm 1100 to 1 120C.
Structural confirmation was given by NMR and IR.
Example 2 N-(((4(2,2-Dichlorn-1 1 -difluoroethoxy)- phenyl)amino)carbonyl)-2-chlorobenzamide 4-(2,2-Dichloro- 1 , 1 -difluoroethoxy)phenylisocyanate (2.54 g) was added to a slurry of 2chlorobenzamide (1.56 g) in dry xylene (50 ml) and the mixture heated under reflux for 24 hours.
The hot, clear solution was cooled, producing a dense mass of colorless needles. The suspension was filtered and the solid washed with coid xylene, 40-60 petrol and dried to give the desired compound (3.22 g, 79 percent), m.p.
1550 to 1560C.
Example 3 Ethyl-4-(2,2-dichloro-1,1 -difluoroethoxy)- phenylcarbamate Ethyl chloroformate (2.23 g) in tetrahydrofuran (15 ml) was added dropwise over 5 minutes to a stirred solution of 4-(2,2-dichloro-1,1 - difluoroethoxy)-aniline (10 g) in tetrahydrofuran (35 ml) at OOC. After stirring for 30 minutes, the resulting suspension was filtered and the clear filtrate was partitioned between ethyl acetate and 2N-HCl (70 ml of each). The organic layer was separated, washed with water, dried and the solvent removed to give a brown oil. After standing for 3 hours at -OOC, the partially solidified oil was triturated with 30-40 petrol (50 ml).The resulting suspension was filtered and the solid product dried to give ethyl 4-(2,2 dichloro- 1 1 -difloroethoxy-phenyl-carbamate (5.6 g, 86 percent), m.p. 900 to 930C.
Elemental analysis percent expected/found: C, 42.04/42.05; H 3.55/3.53; N, 4.45/4.46; Cl, 22.27/22.57; F. 12.21/12.09.
Alternatively, this product was also prepared by adding dropwise a solution of 1,1-dichloro2,2-difluoroethylene (10.2 g) in acetonitrile (10 ml) to a stirred slurry of ethyl 4-hydroxyphenylcarbamate (11.6 g) and potassium hydroxide (2.12 g) in acetonitrile (30 ml) at 50C. The rate of addition was such as to maintain a reaction temperature of less than 80C. The mixture was stirred until the reaction was complete (HPLC).
The reaction mixture was concentrated and partitioned between dichloroemethane (30 ml) and water (50 ml) and the organic layer separated and dried. The solution was made up to a known volume with methanol and assayed by high pressure liquid chromatography (HPLC) against an external standard. The yield was 7.0 g, 35 percent.
A further novel process for the preparation of ethyl 4-(2,2-dichloro-1,1 -difluoroethoxy)phenyl carbamate comprises the addition of 4 (2,2-dichloro-1,1 -difluoroethoxy)phenyl isocyanate (2.68 g) to absolute ethanol (30 ml) at 220C. After standing for 10 minutes, the excess ethanol was removed from the clear reaction mixture under reduced pressure to give a colourless solid (3.0 g, 95 percent).
Example 4 N (((4-(2,2-Dichloro-1 1 -difluoroethoxy- phenyl)amino)carbonyl-2-chlorobenzamide 2-Chlorobenzamide (0.8 g) was added to a solution of ethyl 4-(2,2-dichloro-1,1 - difluoroethoxy)phenyl-carbamate (1.6 g) in odichlorobenzene (25 ml). The resulting slurry was heated under a reflux for five hours. The cooled suspension was dissolved in methanol and made up to a known volume and assayed by HPLC against an external standard. The yield was 22 percent.
Example 5 Ethyl-4-chlorophenylcarbamate Ethyl chloroformate (108.3 g) in tetrahydrofuran (250 ml) was added dropwise over 10 minutes to a stirred solution of 4chlorophenylaniline (128.0 g) and triethylamine (139 ml) at OOC. The resulting suspension was stirred for a further four hours at 0 to 220C. The solids were removed by filtration and the clear filtrate was concentrated to a brown oil which solidified after standing for several hours at OOC.
The product was crystallized from ethanol/water (1:1, 1 liter) to give an off-white solid (145 g, 73 percent), m.p. 690C.
Elemental analysis percent expected/found: C, 54.14/54.17 H, 5.05/5.07; N. 7.02/6.93; Cl, 17.76/17.51.
Example 6 N-( (4-Chlorophenyl )am ino)carbonyl-2chlorobenzamide 2-Chlorobenzamide (0.8 g) was added to a solution of ethyl 4-chlorophenylcarbamate (1.0 g) in o-dichlorobenzene (25 ml). The resulting slurry was heated under reflux for 24 hours. The cooled suspension was dissolved in methanol and made up to a known volume and assayed by HPLC against an external standard of N-((4chlorophenyl)amino)carbonyl-2-chlorobenzamide previously prepared. The yield of the desired compound was 83 percent.
Example 7 N-((4-Chlorophenyl)amino)carbonyl-2- chlorobenzamide 2-Chlorobenzamide (15.5 g) and 4chlorophenyl-isocyanate (16.89 g) in dry xylene (200 ml) were heated to gentle reflux and the ensuing orange solution heated further under reflux for 24 hours. The solution was cooled and a solid formed, 26 g, 84 percent, m.p. 195.50 to 1 960C, filtered and crystallized successively from acetic acid and ethyl acetate, m.p. 1 96.50C to 1 970C.
Found: C, 55.38; H, 3.58; N, 9.49. Required: C, 54.37; H, 3.24; N. 9.06.
Example 8 4-Hydroxyphenylisocyanate To a solution of phosgene (39.6 g) in ethyl acetate (125 ml) at 50 was added a slurry of 4aminophenol (21.89) in ethyl acetate (200 ml).
The reaction was allowed to stand for an hour at 50--200. The resulting clear solution was heated to reflux and phosgene slowly passed into the solution through a gas sparge tube. After 30 minutes the passage of gas was stopped, and the reaction allowed to cool. The ethyl acetate and excess phosgene were removed by atmospheric distillation. The residue was vacuum distilled to give a colourless oil (17.8 g 66%).
Example 9 N-((4-Hydroxyphenyl)amino)carbonyl-2chlorobenza mide A suspension of 2-chlorobenzamide (1.4 g) in dry xylene (35 ml) was treated with 4hydroxyphenylisocyanate (0.6 g) in dry xylene (5 ml) and the resulting mixture heated under reflux for 1 hour. The reaction mixture was cooled and then diluted to known volume with methanol and assayed by HPLC against an external standard.
Yield of desired compound 84%.

Claims (9)

Claims
1. A process for preparing a compound having the general formula:-
wherein X and Y are individually H,F,CI, alkyl or haloalkyl; R and R' are individually H, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, nitro or cyano; wherein T is halogen, halogenated alkyl or the group ZR" wherein R" is H, alkyl aryl, alkyl, halogenated alkyl, halogenated alkylene, pyridyl, substituted pyridyl, phenyl or substituted phenyl and Z is O or S, which comprises reacting an aniline compound having the formula:-
wherein R, R', R" and Tare as above defined with an active carbonyl compound of the formula:-
wherein W is individually Cl, alkoxy or haloalkoxy, optionally in the presence of a tertiary base, and thereafter reacting the resulting compound of the formula::
wherein R, R', R" and Tare as above defined and V is NCO or
wherein W is as above defined with a compound of the formula:-
wherein X and Y are as above defined, at a temperature in the range of from 800 to 1800 C.
2. A process as claimed in claim 1 wherein the compound of the formula:-
wherein V is NHCOW, is prepared by reacting a compound wherein V is NCO with an alkanol of the formula WH.
3. A process as claimed in claim 1 or claim 2, wherein R" is pyridyl substituted with Cl, CF3, NO2, or CN, or phenyl substituted with F, Cl, CF3, NO2 or CN.
4. A process as claimed in any one of the preceding claims which is carried out in an inert aromatic solvent.
5. A process as claimed in claim 4 wherein the solvent is o-dichlorobenzene.
6. A process as claimed in claim 4 wherein the solvent is xylene.
7. A process as claimed in any one of claims 4 to 6 wherein the reaction is carried out at reflux temperature.
8. A process as claimed in claim 1 substantially as hereinbefore described with reference to any one of the Examples.
9. A benzoylphenylurea as defined in claim 1 whenever prepared by a process as claimed in any one of the preceding claims.
GB08128333A 1981-09-18 1981-09-18 Method for making benzoylphenylureas Expired GB2106499B (en)

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GB2106499B GB2106499B (en) 1986-01-02

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4550202A (en) * 1983-01-24 1985-10-29 Duphar International Research B.V. Benzoylurea compounds, and pesticidal and pharmaceutical compositions comprising same
EP0143302A3 (en) * 1983-10-27 1985-12-18 Nihon Tokushu Noyaku Seizo K.K. Benzoylurea derivatives and intermediates
US4567295A (en) * 1983-01-24 1986-01-28 Duphar International Research B.V. Composition active against mites, whitefly and thrips, pharmaceutical composition, and new benzoylurea compounds
EP0176868A1 (en) * 1984-09-29 1986-04-09 Shell Internationale Researchmaatschappij B.V. Benzoyl ureas having an insecticidal activity
US4594451A (en) * 1983-04-22 1986-06-10 Montedison S.P.A. Benzoyl-ureas exerting an insecticide activity
EP0205049A1 (en) * 1985-05-31 1986-12-17 BASF Aktiengesellschaft N-benzoyl-N'-(1,1-difluoro-phenylmethyl)-phenyl ureas, processes for their production and their use in pest control
US4632938A (en) * 1984-02-27 1986-12-30 Takeda Chemical Industries, Ltd. Thiophenylureas, their production and use
US4665235A (en) * 1983-01-24 1987-05-12 Duphar International Research B.V. Benzoylurea compounds, and pesticidal and pharmaceutical compositions comprising same
EP0268952A1 (en) * 1986-11-25 1988-06-01 Bayer Ag Benzoyl(thio) ureas
WO1993004044A1 (en) * 1991-08-20 1993-03-04 Korea Research Institute Of Chemical Technology Pyrazole containing benzoyl urea derivatives, composition and use
US5210100A (en) * 1984-08-31 1993-05-11 Ciba-Geigy Corporation Phenylbenzoylureas

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4710516A (en) * 1983-01-24 1987-12-01 Duphar International Research B.V. Insecticidal and acaricidal composition comprising a benzoylurea compound
US4567295A (en) * 1983-01-24 1986-01-28 Duphar International Research B.V. Composition active against mites, whitefly and thrips, pharmaceutical composition, and new benzoylurea compounds
US4550202A (en) * 1983-01-24 1985-10-29 Duphar International Research B.V. Benzoylurea compounds, and pesticidal and pharmaceutical compositions comprising same
US4609676A (en) * 1983-01-24 1986-09-02 Duphar International Research B.V. Benzoylurea compounds, and pesticidal and pharmaceutical compositions comprising same
US4665235A (en) * 1983-01-24 1987-05-12 Duphar International Research B.V. Benzoylurea compounds, and pesticidal and pharmaceutical compositions comprising same
US4594451A (en) * 1983-04-22 1986-06-10 Montedison S.P.A. Benzoyl-ureas exerting an insecticide activity
EP0143302A3 (en) * 1983-10-27 1985-12-18 Nihon Tokushu Noyaku Seizo K.K. Benzoylurea derivatives and intermediates
US4632938A (en) * 1984-02-27 1986-12-30 Takeda Chemical Industries, Ltd. Thiophenylureas, their production and use
US5210100A (en) * 1984-08-31 1993-05-11 Ciba-Geigy Corporation Phenylbenzoylureas
EP0176868A1 (en) * 1984-09-29 1986-04-09 Shell Internationale Researchmaatschappij B.V. Benzoyl ureas having an insecticidal activity
US5607977A (en) * 1984-09-29 1997-03-04 Shell Agrar Gmbh & Co. Kg Benzoylureas
EP0205049A1 (en) * 1985-05-31 1986-12-17 BASF Aktiengesellschaft N-benzoyl-N'-(1,1-difluoro-phenylmethyl)-phenyl ureas, processes for their production and their use in pest control
EP0268952A1 (en) * 1986-11-25 1988-06-01 Bayer Ag Benzoyl(thio) ureas
WO1993004044A1 (en) * 1991-08-20 1993-03-04 Korea Research Institute Of Chemical Technology Pyrazole containing benzoyl urea derivatives, composition and use

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PCNP Patent ceased through non-payment of renewal fee

Effective date: 19970918