CA1092125A - Process for preparing amino-phenyl-ureas and amino- carbanylates - Google Patents
Process for preparing amino-phenyl-ureas and amino- carbanylatesInfo
- Publication number
- CA1092125A CA1092125A CA294,489A CA294489A CA1092125A CA 1092125 A CA1092125 A CA 1092125A CA 294489 A CA294489 A CA 294489A CA 1092125 A CA1092125 A CA 1092125A
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- urea
- methyl
- ethyl
- chloro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C273/00—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups
- C07C273/18—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas
- C07C273/1854—Preparation of urea or its derivatives, i.e. compounds containing any of the groups, the nitrogen atoms not being part of nitro or nitroso groups of substituted ureas by reactions not involving the formation of the N-C(O)-N- moiety
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
ABSTRACT OF THE DISCLOSURE :
Process for preparing aminophenyl-ureas and amino-carbanylates by direct amination of phenylureas and carbanylates respectively by means of N-chloro-amines, in a redox type system, in an acid reaction medium.
Process for preparing aminophenyl-ureas and amino-carbanylates by direct amination of phenylureas and carbanylates respectively by means of N-chloro-amines, in a redox type system, in an acid reaction medium.
Description
~L~9Z~L~5 This invention relates to a particularly sirnple and selective process for preparing amino-phenyl-ureas and arnino-carbanylates.
- Such products are of great interest in the field of the fine chemi~als and chiefly in that of the dyes, as they are basic intermediates for the dyes synthesis. In particular they are useful as herbicides and as coupling compounds in the preparation of the azo dyes, as is described, for example, in Belgian patent.s Ns. 694,733, 702,400 and 694,633.
The process of the present invention is prac-ticed by treating the phenyl-ureas or the carbanylates in suitable acid solvents, such as sulphuric acid, trifluoroacetic acid or mixtures thereof with acetic acid, with a suited N-halogen amine, and with a redox system containing salts, such as, e.g., ferrous, titanous or cuprous salts, at more or less low temperatures, for example around the room temperature.
; The phenyl-ureas and the carbanylates can be substituted at the nitrogen, for example, by alkyls, aralkyls, cycloalkyls, aryls, optionally suhstituted. Also, phenyl can be substituted, for instance, by halogens, alkyls, a nitro-group, a cyano-group, a hydroxyl, an alkoxyl, optionally substituted.
The method of synthetising aromatic N-alkyl-amines ; by amination of aromatic substrates with N-chloro-amines, in the presence of a reducing salt in an acid reaction medïum, has been described in US patent N. 3,483,255, where aromatic compounds either not substituted or monosubstituted with chlorine, bromine, iodine, -OCH3 are alkylaminated.
It was expectable that, by operating according to said method, N-chloro-ureas and chlorination products of the side chains in the substituted ureas should form.
For the carbanylates-too it was expectable that, by operating according to said method, by-products should form, - 1 - '"~
~z~s such as, e.g. N-chloro-carbanylates, chlorination products of the side chains in the substituted carbanylates, and furthermore that the carbanylates could be hydrolised in the reaction conditions.
It has now been surprisingly found that the new synthesis method of the present invention does not cause the formation of the above-said products, but rather is accompanied by high yields and a high selectivity for preparing substituted aminobenzenes, either using phenyl-ureas or carbanylates, or using phenyl-substituted phenyl-ureas and carbanylates~
It is an object of the present invention to provide a particularly simple industrial process for the production of substituted amino benzenes, which permits to obtain products whose synthesis according to conventional methods is usually very difficult.
Other objects of the invention will be apparent from the discussion which follows.
In general, the process of this invention relates to a process for preparing aminophenyl-ureas and amino~carbanylates by direct amination of phenylureas and carbanylates respectively by means of N-chloro-amines, in a redox type system, in an acid reaction medium.
The reaction occurs in a very broad temper-ature range: from -60 to +100C; good results are achieved for example, between 0C and ~0C.
The molar ratios between N-chloro-amine and aromatic substrate (phenyl-ureas or carbanylates) vary as a function of the synthe5~s: generally they may range from 1:3 to 3:1.
The catalyst may vary in respect oE N-chloro-amine .. ,,j ~J' ~0~2~S
from 1:1 to 1:100 by mols, according to the case, preferably from 1:1,2 to 1:50.
Also with regard to the acid mixture, it is possible to employ the most different ratios in respect of the aromatic substrate~
A high selectivity and good yields can be achieved, in several cases, by using 300 to 1000 ml for each mole of such aromatic substrate.
Using H2S04, the best results are attained at a concentration by weight of H2S04 equal to at least 25%.
A way of conducting the process is the following.
Into a reactor equipped with stirrer, thermometer, tap funnel and cooler, there are introduced :
- the acid mixture - the phenyl-urea of the carbanylate - the N-chloro-amine dissolved in an acid mixture - the catalyst.
At the conclusion of the reaction, the reactor contents are poured onto ice, under stirring, and the starting product, if still present, is extracted from the acid solution by means of a proper solvent, for example chloroform, CC14, ethyl acetate, ethyl ether, toluene, chlorobenzene, dichloro-benzene, nitrobenzene, cyclohexane, etc.
After alkalinization with a concentrated al]caline sol-ution, for example caustic soda at 30%, the reaction product is extracted.
Use is made of the solvent most ~uitcd ~o each case, Tho selection is essentially bound to the coefficient of distribution of the product between solvent and aqueous solution.
Some employable solvents are, for example: chloroform, carbon tetrachloride, ethyl ether, toluene, cyclohexane, etc.
After distillation of the solvent, the finished products are obtained generally at a purity degree already useful for the successive uses. In some cases it may be useful to effect a crystallization from a proper solvent or a frac-tionated precipitation such as hydrochlori~e, sulphate, phosphate, etc.
As N-halogen-amine it is possible to use, for instance:
- N-chloro-methyl amine - N-chloro-dimethyl-amine - N-chloro-methyl-ethylamine - N-chloro-methyl-benzyl-amine - N-chloro-diethyl-amine - N-chloro-chloro-morpholine - N-chloro-piperidine and the like.
Employable phenyl-ureas are, for example :
; - N-phenyl-urea - N-methyl-N-phenyl-urea - N-phenyl-N'-methyl-urea - N-phenyl-N',N'-dime-thyl-urea - N-methyl-N-phenyl-N'-methyl-urea - N-methyl-N-phenyl-N',N'-dimethyl-urea - N-phenyl-N'-ethyl-urea - N-ethyl-N-phenyl-urea - N-phenyl-N', N'-diethyl-urea - N-ethyl-N-phenyl-N'ethyl- urea - N-ethyl-N-phenyl-N',N'-diethyl-urea - N-phenyl-N'-phenyl-urea - N-methyl-N-phenyl-N'-phenyl-urea - N-methyl-N-phenyl-N'-methyl-N'-phenyl-urea - N-ethyl-N-phenyl-N'-phenyl-urea - N-ethyl-N-phenyl-N'-ethyl-N'-phenyl-urea - N-phenyl-N'-ethyl-N'-phenyl-urea - N-methyl-N-phenyl-N',N'-diethyl~urea 9Z~ZS
- N-methyl-N-phenyl-N'-methyl-N'-ethyl-urea - N-ethyl-N-phenyl-N'-methyl-N'-ethyl-urea - N-ethyl-N-phenyl-N',N' dimethyl-urea - N-ethyl-N-phenyl-N'-methyl-N'-ethyl-urea - N-phenyl-N'-phenyl-N'-methyl-urea - N-phenyl-N'-ethyl-N'-phenyl-urea - N-methyl-N-phenyl-N'-methyl-N'-ethyl-urea - N-methyl-N-phenyl-N'-methyl-N'phenyl-urea - N-methyl-N-phenyl-N'-ethyl-N'-phenyl-urea - N-ethyl-N-phenyl-N'-methyl-N'-ethyl urea - N-ethyl-N-phenyl-N'-methyl-N'phenyl-urea - N-ethyl-N-phenyl-N'-ethyl-N'phenyl-urea - N-2-nitro-phenyl-urea - N-2-chloro-phenyl-urea - N-2-bromo-phenyl-urea - N-2-iodo-phenyl-urea - N-2-methyl-phenyl-urea : - N-2-isopropyl-phenyl-urea - N-2-chloro-phenyl-N-methyl-N'-ethyl-urea - N-2-methyl-phenyl-N',N'-dimethyl-urea - M-2-methyl-phenyl-N'-2-methyl-phenyl-urea - N-2-cyano-phenyl-urea - N-2-acetoamino-phenyl-urea - N-2-methoxy-phenyl-urea - N-2-methoxy-phenyl-N',N'-dimethyl-urea - N-2-methoxy-phenyl-N'-ethyl-urea - N-2-methoxy-phenyl-N',N'-diethyl-urea - - N-methyl-N-2-ethoxy-phenyl-urea - N-2-hydroxy-phenyl-urea - N-3-chloro-phenyl-urea - N-3-methyl-phenyl-urea - N-methyl-N-3-chloro-phenyl-urea ~Z~2S
- N-ethyl-N-3-chloro-phenyl-urea - N-methyl-N-3-chloro-phenyl-N'-dimethyl-urea - N-3-chloro-phenyl-N',N'-diethyl-urea - N-3-methyl-phenyl-N',N'-diethyl-urea - N-3-ethoxy-phenyl-urea or N-3-methoxy-phenyl-urea - N-3-hydroxy-phenyl-urea - N-2-tert.-butyl-phenyl-urea - N-3-nethoxy-phenyl-N',N'-diethyl-urea - N-methyl-N-3-methoxy-pherlyl-urea - N-4-chloro-phenyl-urea - N-4-methyl-phenyl-urea - N-4-hydroxy-phenyl-urea - N-4-methoxy-phenyl-urea - N-4-ethoxy-phenyl-urea - N-4-acetamino-phenyl-urea - N-4-ureido-phenyl-urea - N-ethyl-N-4-chloro-phenyl-N',N'-diethyl-urea - N-methyl-N-4-methoxy-phenyl-urea - N-4-methoxy-phenyl-N',N'-dimethyl-urea - N-4-methoxy-phenyl-N'-ethyl-urea - N-4-methoxy-phenyl-N'-methyl-urea - N-methyl-N-4-methoxy-phenyl-N',N'-dimethyl-urea - N-methyl-N-4-methoxy-phenyl-N',N'-diethyl-urea - N-4-ethoxy-phenyl-N'-ethyl-urea - N-4-ethoxy-phenyl-N',N'-dimethyl-urea - N-ethyl-N-4-ethoxy-phenyl-N',N'-diethyl-urea - N-2.5-dimethoxy-phenyl-urea - N-2.5-dimethyl-phenyl-urea - N-4-methoxy-phenyl~N'/4'-methoxy-phenyl-urea - N-4-ethoxy-phenyl-N'-4'-ethoxy-phenyl-urea - N-phenyl-N'-3',5'-dinitro-phenyl-urea - N-4-methyl-phenyl-N'-3'-5'-dinitro-phenyl-urea ~39Z12S
- N-~-ethoxy-phenyl-N'-3'-5'-dinitro-phenyl-urea - N-4-methoxy-phenyl-N'-3'-5'-dinitro-phenyl-urea - N-phenyl-N'-3'-5'-dicyano-phenyl-urea - N-4-methyl-phenyl-N'-3'-5'-dicyano-phenyl-urea - N-4-methoxy phenyl-N'-3'-5'-dicyano-phenyl-urea - N-4-ethoxy-phenyl-N'-3',5'-dicyano-phenyl-urea - N-phenyl-N'-3'-nitro-5'-cyano-phenyl-urea - N-phenyl-N'-chloroethyl-urea - N-phenyl-N'-cyanoethyl-urea - N-phenyl-N'-sulphopropyl-urea - N-phenyl-N'-hydroxyphentyl-urea - N-phenyl-N'-ethoxy-valeryl-ùrea - N-phenyl-N'-aminobutyl-urea - N-methyl-N-phenyl-N'-hydroxypropyl-urea - N-ethyl-N-4-ethoxy-phenyl-N'-sulphopropyl-urea - N-4-ethoxy-phenyl-N'-cyanoethyl-urea - N-4-(2-hydroxy-ethoxy)-phenyl-N'-hydroxy-ethyl-urea - ~-methyl-N-4-methyl-propionatoxy-phenyl-N'-chloroethyl-urea - N-4-~2-hydroxy-ethoxy)-phenyl-urea - N-4-methyl-pripionatoxy-phenyl-urea - N-4-cyanoethoxy-phenyl-urea - N-4-cyclohexoxy-phenyl-urea - N-4-methoxy-pripionyl-oxy-phenyl-urea - N-4-(2-ethoxy-ethoxy)-phenyl-urea - N-4-isopropoxy-phenyl-urea N-4 t-butoxy-phenyl-urea - N-methyl-N-4-cyclohexoxy-phenyl-urea - N-methyl-N-4-(2-hydroxy-ethoxy)-phenyl-urea - N-ethyl-N-4-methyl-propionatoxy-phenyl-urea - N ethyl-N-phenyl-N'-cyclohexyl-urea - N-phenyl-N'-cyclohexyl-urea ~19~2~25 - N-4-methoxy-phenyl-N'-cyclohexyl-urea - N-methyl-N-4-ethoxy-phenyl-N'-cyclohexyl-urea -~ N-ethyl-N-4-methoxy-phenyl-N'-cyclohexyl-urea - N-4-cyclohexoxy-phenyl-N'-cyclohexyl-urea - N-ethyl-N-4-(2-hydroxy-ethoxy)-phenyl-N'-cyclohexyl-urea - N-methyl-N-phenyl-N'-ethyl-urea.
Employable carbanylates may be the derivatives of methyl or ethyl carbanylate, such as ~or example:
- N-methyl-methyl carbanylate - 4-methoxy-methyl carbanylate - N-methyl-~-methoxy-methyl carbanylate - N-ethyl-methyl carbanylate - N-ethyl-4-methoxy-methyl carbanylate
- Such products are of great interest in the field of the fine chemi~als and chiefly in that of the dyes, as they are basic intermediates for the dyes synthesis. In particular they are useful as herbicides and as coupling compounds in the preparation of the azo dyes, as is described, for example, in Belgian patent.s Ns. 694,733, 702,400 and 694,633.
The process of the present invention is prac-ticed by treating the phenyl-ureas or the carbanylates in suitable acid solvents, such as sulphuric acid, trifluoroacetic acid or mixtures thereof with acetic acid, with a suited N-halogen amine, and with a redox system containing salts, such as, e.g., ferrous, titanous or cuprous salts, at more or less low temperatures, for example around the room temperature.
; The phenyl-ureas and the carbanylates can be substituted at the nitrogen, for example, by alkyls, aralkyls, cycloalkyls, aryls, optionally suhstituted. Also, phenyl can be substituted, for instance, by halogens, alkyls, a nitro-group, a cyano-group, a hydroxyl, an alkoxyl, optionally substituted.
The method of synthetising aromatic N-alkyl-amines ; by amination of aromatic substrates with N-chloro-amines, in the presence of a reducing salt in an acid reaction medïum, has been described in US patent N. 3,483,255, where aromatic compounds either not substituted or monosubstituted with chlorine, bromine, iodine, -OCH3 are alkylaminated.
It was expectable that, by operating according to said method, N-chloro-ureas and chlorination products of the side chains in the substituted ureas should form.
For the carbanylates-too it was expectable that, by operating according to said method, by-products should form, - 1 - '"~
~z~s such as, e.g. N-chloro-carbanylates, chlorination products of the side chains in the substituted carbanylates, and furthermore that the carbanylates could be hydrolised in the reaction conditions.
It has now been surprisingly found that the new synthesis method of the present invention does not cause the formation of the above-said products, but rather is accompanied by high yields and a high selectivity for preparing substituted aminobenzenes, either using phenyl-ureas or carbanylates, or using phenyl-substituted phenyl-ureas and carbanylates~
It is an object of the present invention to provide a particularly simple industrial process for the production of substituted amino benzenes, which permits to obtain products whose synthesis according to conventional methods is usually very difficult.
Other objects of the invention will be apparent from the discussion which follows.
In general, the process of this invention relates to a process for preparing aminophenyl-ureas and amino~carbanylates by direct amination of phenylureas and carbanylates respectively by means of N-chloro-amines, in a redox type system, in an acid reaction medium.
The reaction occurs in a very broad temper-ature range: from -60 to +100C; good results are achieved for example, between 0C and ~0C.
The molar ratios between N-chloro-amine and aromatic substrate (phenyl-ureas or carbanylates) vary as a function of the synthe5~s: generally they may range from 1:3 to 3:1.
The catalyst may vary in respect oE N-chloro-amine .. ,,j ~J' ~0~2~S
from 1:1 to 1:100 by mols, according to the case, preferably from 1:1,2 to 1:50.
Also with regard to the acid mixture, it is possible to employ the most different ratios in respect of the aromatic substrate~
A high selectivity and good yields can be achieved, in several cases, by using 300 to 1000 ml for each mole of such aromatic substrate.
Using H2S04, the best results are attained at a concentration by weight of H2S04 equal to at least 25%.
A way of conducting the process is the following.
Into a reactor equipped with stirrer, thermometer, tap funnel and cooler, there are introduced :
- the acid mixture - the phenyl-urea of the carbanylate - the N-chloro-amine dissolved in an acid mixture - the catalyst.
At the conclusion of the reaction, the reactor contents are poured onto ice, under stirring, and the starting product, if still present, is extracted from the acid solution by means of a proper solvent, for example chloroform, CC14, ethyl acetate, ethyl ether, toluene, chlorobenzene, dichloro-benzene, nitrobenzene, cyclohexane, etc.
After alkalinization with a concentrated al]caline sol-ution, for example caustic soda at 30%, the reaction product is extracted.
Use is made of the solvent most ~uitcd ~o each case, Tho selection is essentially bound to the coefficient of distribution of the product between solvent and aqueous solution.
Some employable solvents are, for example: chloroform, carbon tetrachloride, ethyl ether, toluene, cyclohexane, etc.
After distillation of the solvent, the finished products are obtained generally at a purity degree already useful for the successive uses. In some cases it may be useful to effect a crystallization from a proper solvent or a frac-tionated precipitation such as hydrochlori~e, sulphate, phosphate, etc.
As N-halogen-amine it is possible to use, for instance:
- N-chloro-methyl amine - N-chloro-dimethyl-amine - N-chloro-methyl-ethylamine - N-chloro-methyl-benzyl-amine - N-chloro-diethyl-amine - N-chloro-chloro-morpholine - N-chloro-piperidine and the like.
Employable phenyl-ureas are, for example :
; - N-phenyl-urea - N-methyl-N-phenyl-urea - N-phenyl-N'-methyl-urea - N-phenyl-N',N'-dime-thyl-urea - N-methyl-N-phenyl-N'-methyl-urea - N-methyl-N-phenyl-N',N'-dimethyl-urea - N-phenyl-N'-ethyl-urea - N-ethyl-N-phenyl-urea - N-phenyl-N', N'-diethyl-urea - N-ethyl-N-phenyl-N'ethyl- urea - N-ethyl-N-phenyl-N',N'-diethyl-urea - N-phenyl-N'-phenyl-urea - N-methyl-N-phenyl-N'-phenyl-urea - N-methyl-N-phenyl-N'-methyl-N'-phenyl-urea - N-ethyl-N-phenyl-N'-phenyl-urea - N-ethyl-N-phenyl-N'-ethyl-N'-phenyl-urea - N-phenyl-N'-ethyl-N'-phenyl-urea - N-methyl-N-phenyl-N',N'-diethyl~urea 9Z~ZS
- N-methyl-N-phenyl-N'-methyl-N'-ethyl-urea - N-ethyl-N-phenyl-N'-methyl-N'-ethyl-urea - N-ethyl-N-phenyl-N',N' dimethyl-urea - N-ethyl-N-phenyl-N'-methyl-N'-ethyl-urea - N-phenyl-N'-phenyl-N'-methyl-urea - N-phenyl-N'-ethyl-N'-phenyl-urea - N-methyl-N-phenyl-N'-methyl-N'-ethyl-urea - N-methyl-N-phenyl-N'-methyl-N'phenyl-urea - N-methyl-N-phenyl-N'-ethyl-N'-phenyl-urea - N-ethyl-N-phenyl-N'-methyl-N'-ethyl urea - N-ethyl-N-phenyl-N'-methyl-N'phenyl-urea - N-ethyl-N-phenyl-N'-ethyl-N'phenyl-urea - N-2-nitro-phenyl-urea - N-2-chloro-phenyl-urea - N-2-bromo-phenyl-urea - N-2-iodo-phenyl-urea - N-2-methyl-phenyl-urea : - N-2-isopropyl-phenyl-urea - N-2-chloro-phenyl-N-methyl-N'-ethyl-urea - N-2-methyl-phenyl-N',N'-dimethyl-urea - M-2-methyl-phenyl-N'-2-methyl-phenyl-urea - N-2-cyano-phenyl-urea - N-2-acetoamino-phenyl-urea - N-2-methoxy-phenyl-urea - N-2-methoxy-phenyl-N',N'-dimethyl-urea - N-2-methoxy-phenyl-N'-ethyl-urea - N-2-methoxy-phenyl-N',N'-diethyl-urea - - N-methyl-N-2-ethoxy-phenyl-urea - N-2-hydroxy-phenyl-urea - N-3-chloro-phenyl-urea - N-3-methyl-phenyl-urea - N-methyl-N-3-chloro-phenyl-urea ~Z~2S
- N-ethyl-N-3-chloro-phenyl-urea - N-methyl-N-3-chloro-phenyl-N'-dimethyl-urea - N-3-chloro-phenyl-N',N'-diethyl-urea - N-3-methyl-phenyl-N',N'-diethyl-urea - N-3-ethoxy-phenyl-urea or N-3-methoxy-phenyl-urea - N-3-hydroxy-phenyl-urea - N-2-tert.-butyl-phenyl-urea - N-3-nethoxy-phenyl-N',N'-diethyl-urea - N-methyl-N-3-methoxy-pherlyl-urea - N-4-chloro-phenyl-urea - N-4-methyl-phenyl-urea - N-4-hydroxy-phenyl-urea - N-4-methoxy-phenyl-urea - N-4-ethoxy-phenyl-urea - N-4-acetamino-phenyl-urea - N-4-ureido-phenyl-urea - N-ethyl-N-4-chloro-phenyl-N',N'-diethyl-urea - N-methyl-N-4-methoxy-phenyl-urea - N-4-methoxy-phenyl-N',N'-dimethyl-urea - N-4-methoxy-phenyl-N'-ethyl-urea - N-4-methoxy-phenyl-N'-methyl-urea - N-methyl-N-4-methoxy-phenyl-N',N'-dimethyl-urea - N-methyl-N-4-methoxy-phenyl-N',N'-diethyl-urea - N-4-ethoxy-phenyl-N'-ethyl-urea - N-4-ethoxy-phenyl-N',N'-dimethyl-urea - N-ethyl-N-4-ethoxy-phenyl-N',N'-diethyl-urea - N-2.5-dimethoxy-phenyl-urea - N-2.5-dimethyl-phenyl-urea - N-4-methoxy-phenyl~N'/4'-methoxy-phenyl-urea - N-4-ethoxy-phenyl-N'-4'-ethoxy-phenyl-urea - N-phenyl-N'-3',5'-dinitro-phenyl-urea - N-4-methyl-phenyl-N'-3'-5'-dinitro-phenyl-urea ~39Z12S
- N-~-ethoxy-phenyl-N'-3'-5'-dinitro-phenyl-urea - N-4-methoxy-phenyl-N'-3'-5'-dinitro-phenyl-urea - N-phenyl-N'-3'-5'-dicyano-phenyl-urea - N-4-methyl-phenyl-N'-3'-5'-dicyano-phenyl-urea - N-4-methoxy phenyl-N'-3'-5'-dicyano-phenyl-urea - N-4-ethoxy-phenyl-N'-3',5'-dicyano-phenyl-urea - N-phenyl-N'-3'-nitro-5'-cyano-phenyl-urea - N-phenyl-N'-chloroethyl-urea - N-phenyl-N'-cyanoethyl-urea - N-phenyl-N'-sulphopropyl-urea - N-phenyl-N'-hydroxyphentyl-urea - N-phenyl-N'-ethoxy-valeryl-ùrea - N-phenyl-N'-aminobutyl-urea - N-methyl-N-phenyl-N'-hydroxypropyl-urea - N-ethyl-N-4-ethoxy-phenyl-N'-sulphopropyl-urea - N-4-ethoxy-phenyl-N'-cyanoethyl-urea - N-4-(2-hydroxy-ethoxy)-phenyl-N'-hydroxy-ethyl-urea - ~-methyl-N-4-methyl-propionatoxy-phenyl-N'-chloroethyl-urea - N-4-~2-hydroxy-ethoxy)-phenyl-urea - N-4-methyl-pripionatoxy-phenyl-urea - N-4-cyanoethoxy-phenyl-urea - N-4-cyclohexoxy-phenyl-urea - N-4-methoxy-pripionyl-oxy-phenyl-urea - N-4-(2-ethoxy-ethoxy)-phenyl-urea - N-4-isopropoxy-phenyl-urea N-4 t-butoxy-phenyl-urea - N-methyl-N-4-cyclohexoxy-phenyl-urea - N-methyl-N-4-(2-hydroxy-ethoxy)-phenyl-urea - N-ethyl-N-4-methyl-propionatoxy-phenyl-urea - N ethyl-N-phenyl-N'-cyclohexyl-urea - N-phenyl-N'-cyclohexyl-urea ~19~2~25 - N-4-methoxy-phenyl-N'-cyclohexyl-urea - N-methyl-N-4-ethoxy-phenyl-N'-cyclohexyl-urea -~ N-ethyl-N-4-methoxy-phenyl-N'-cyclohexyl-urea - N-4-cyclohexoxy-phenyl-N'-cyclohexyl-urea - N-ethyl-N-4-(2-hydroxy-ethoxy)-phenyl-N'-cyclohexyl-urea - N-methyl-N-phenyl-N'-ethyl-urea.
Employable carbanylates may be the derivatives of methyl or ethyl carbanylate, such as ~or example:
- N-methyl-methyl carbanylate - 4-methoxy-methyl carbanylate - N-methyl-~-methoxy-methyl carbanylate - N-ethyl-methyl carbanylate - N-ethyl-4-methoxy-methyl carbanylate
- 2-nitro-methyl carbanylate - 2-chloro-methyl carbanylate - 2-bromo-methyl carbanylate - 2-iodine-methyl carbanylate - 2-methyl-methyl carbanylate - 2-ethyl-methyl carbanylate - 2-isopropyl-methyl carbanylate - 2-tert.butyl-methyl carbanylate - N-methyl-2-chloro-methyl carbanylate - N-ethyl-2-methyl-methyl carbanylate - 2-cyano-methyl carbanylate - 2-methoxy-methyl carbanylate - 2-hydroxy-methyl carbanylate - 2-ethoxy-methyl carbanylate - N-ethyl-2-ethoxy-methyl carbanylate N-methyl-2-acetylamino-methyl carbanylate
- 3-chloro-methyl carbanylate - 3-methyl-methyl carbanylate )9;~ S
- 3-methoxy-methyl carba:nylate - 3-hydroxy-methyl carbanylate - 3-ethoxy-methyl carbanylate - N-methyl-3-methoxy-methyl carbanylate - N-methyl-3-methyl-methyl carbanylate - N-ethyl-3-ethoxy-methyl carbanylate ~ N-ethyl-3-methoxy-methyl carbanylate
- 3-methoxy-methyl carba:nylate - 3-hydroxy-methyl carbanylate - 3-ethoxy-methyl carbanylate - N-methyl-3-methoxy-methyl carbanylate - N-methyl-3-methyl-methyl carbanylate - N-ethyl-3-ethoxy-methyl carbanylate ~ N-ethyl-3-methoxy-methyl carbanylate
- 4-chloro-methyl carbanylate - 4-methoxy-methyl carbanylate - 4-methyl-methyl carbanylate - 4-ethoxy-methyl carbanylate - 2.5-dimethoxy~methyl carbanylate - 2.5-dimethyl-methyl carbanylate - 4(beta-hydroxy~-ethoxy-methyl carbanylate - 4-methoxypropionyl-oxy-methyl carbanylate - 4-(beta-cyano~-ethoxy-methyl carbanylate - 4-cyclohexyloxy-methyl carbanylate - 4-(beta-ethoxy)-ethoxy-methyl carbanylate - 4-isopropyl-oxy-methyl carbanylate - 4-t-butyl-oxy-methyl carbanylate - N-cyclohexyl-methyl carbanylate - N-ethyl-4-ethoxy-methyl carbanylate - N-cyclohexyl-4-methoxy-methyl carbanylate - N-ethyl-4-cyclohexyl-oxy-methyl carbanylate - N-methyl-4-(beta-cyano)-ethoxy-methyl carbanylate - N-ethyl-4-(beta-hydroxy)~ethoxy-methyl carbanylate - N-methyl-4-methoxy-pripionyl-oxy-methyl carbanylate - N-ethyl-4-(beta-ethoxy)-ethoxy-me-thyl carbanylate.
For the compounds listed hereinbefore it is understood that the methyl of the ester group can be substituted by an ethyl.
Other employable carbanylates are for exam~le :
_ g _ ~LQ~2~XS
- beta-chloro-ethyl earbanylate - beta-cyano-ethyl carbanylate - propyl earbanylate - isopropyl carbanylate - tert.-butyl earbanylate - eyelohexyl carbanylate - beta-hydroxy-ethyl earbanylate - beta-ehloro-ethyl N-methyl-earbanylate - eyelohexyl N-ethyl-earbanylate - eyclohexyl N-eyelohexyl-carbanylate - beta-eyano-ethyl N-methyl-carbanylate - propyl 4-methoxy-carbanylate - tert.-butyl 4-methoxy-carbanylate - isopropyl N-methyl-4-methoxy-carbanylate - N-cyelohexyl-4-cyclohexyl-oxy-eyelohexyl earbanylate - N-ethyl-4-ethoxy beta eyano-ethyl earbanylate.
The proeess for aminating phenyl~ureas ean be represent-ed as follows:
~ _ e - N ~ \ R
N - I - N
Rl N
wherein :
- R and Rl, like or unlike eaeh other, may be hydrogen or an alkyl, eyeloalkyl, aryl, arylkyl, optionally substituted, - R2 may be hydrogen or an alkyl, eye].oalkyl, aryl, aralkyl, 2~L25 optionally substituted;
- R3 and R4, like or unlike each other, may be alkyl, cyclo-alkyl, aralkyl, optionally substituted and furthermore one of the two, either R3 or R4, may be hydrogen. R3 and R4 may also be the residue of a cyclo, optionally substituted, containing or not containing other hetero-atoms;
- A is a benzene ring either or not containing substituents, with at least a free position.
The substituents of Rl, R2, R3, R4 and A may be, for example, halogen, nitrile, sulphonic, carboxylic groups and esters thereof, amino-hydroxyl, alkyl, alkyl-substituted, alkoxyl, alkoxyl-substituted, acylamino, cycloalkyloxy, ureic groups, etc.' in particular the substituents of the alkyl and alkoxyl groups may be, for example, halogen, hydroxyl, carboxylic, sulphoric groups and esters thereof, a nitrile, an alkoxyl.
When Rl, R2, R3 and R4 mean an alkyl or an alkoxyl, their alkyl chains contain preferably 1 to 5 carbon atoms.
The process for aminating the carbanylates with N-chloro-amines can be represented as follows:
O O R
\ / ~ ~> + Cl - N~ ~0 ,N~
wherein :
Rl, R2 may be, for example, an alkyl or cycloalkyl, an aryl, an aralkyl, optionally substituted;
30 R2 may be also hydrogen, R3, R4 may, for example, an alkyl or cycloalkyl, an aralkyl, optionally substituted, and furthermore one of the two Z~,Z~
may be also hydrogen, R3, R4 may constitute the residue of a cyclo, optionally substituted, either or not containing hetero-atoms;
A is a benzene nucleus, having at least a free position.
The substituents of Rl, R2, R3, R4 and A, may be, for example, halogen, nitrile, sulphonic, carboxylic groups and esters thereof, amino, hydroxyl, alkyl, alkyl-substituted, alkoxyl, alkoxyl-substituted, acylamino, cycloalkyloxy, ureic groups, etc.; furthermore the substituen-ts of the alkyls and alkoxyls may be, for instance, halogen, hydroxyl, carboxylic, sulphonic groups and esters thereof, nitrile, oxygen-alkyl.
When Rl, R2, R3, R~ mean an alkyl or an alkoxyl, their alkyl chains contain preferably from 1 to 5 carbon atoms.
In accordance with the process of this invention when a substituted benzene reactant is a phenyl urea type, such as:
N-phenyl-urea ; N-phenyl-N'-ethyl-urea N-methyl-N-phenyl-N',N'-dimethyl-urea N-methyl-N-phenyl-N'-ethyl-urea a selective linking in para position in respect of nitrogen in A is obtained.
If phenyl is substituted in para position, i.e. if products of the following type are used:
N-4-methoxy-phenyl-urea N-4-methoxy-phenyl-N'-ethyl-urea N-4-ethoxy-phenyl-N'-ethyl-urea N-4-hydroxy-phenyl-urea N-4-cyclohexoxy-phenyl-N',N'-dimethyl-urea N-methyl-N-4-chloro-phenyl-urea N-4-ethoxy-phenyl-N',N'-dimethyl-urea a selective linking in meta position in respect of N in A is obtained.
~0~2~S
Conversely, if phenyl is substi-tuted in ortho position, i.e. if products of the following -type are used:
N-2-methyl-phenyl-urea N-2-methyl-phenyl-N',N'-dimethyl-urea N-2-chloro-phenyl-N'-ethyl-urea ~-methyl-N-2-bromo-phenyl-urea, etc.
a selective linking in para position in respect o nitrogen in A is obtained.
As to the carbanylates, when starting products such as:
methyl carbanylate ethyl carbanylate N-methyl-ethyl carbanylate N-ethyl-methyl carbanylate are used, a selective linking in para position in respect of nitrogen in A is obtained.
If phenyl is substituted in para position, i.e. if products of the following type are utilized:
4-methoxy-methyl carbanylate ~ 4-ethoxy-methyl carbanylate 4-methoxy-ethyl carbanylate 4-ethoxy-ethyl carbanylate N-methyl-4-methoxy-methyl carbanylate, a selective linking in meta position in respect of nitrogen in A is obtained.
Conversely, if phenyl is substituted in ortho position, i.e. if products such as the following ones are used:
2-methyl-methyl carbanylatc 2-chloro-ethyl carbanylate 2-methyl-ethyl carbanylate a selective linking in para position in respect of nitrogen in A is obtained.
The following examples are given merely to illustrate 1~1392~Z5 the present invention and are not intended to limit more general aspects thereof.
In such examples, unless otherwise specified, the term "parts"
is to be understood as expressed in units by weight.
For the examples relating to phenyl-ureas, the yield is cal-culated on the amount of N-chloro-amine used, while for the examples concerning the carbanylates, the yield is calculated on the amount of converted carbanylate.
A) Preparation of amino-phenyl-ureas Into a reactor equipped with stirrer, cooler, thermo-meter and dropping funnel, 60 parts of concentrated H2S04 were charged and, keeping the temperature below 10C, 8.2 parts of N-phenyl-N'-ethyl-urea were charged.
Successively, under stirring, there were added thereto 41.7 parts of a sulphuric solution of N-chloro-dimethyl-amine at 9.65%, corresponding to 4 parts at 100%.
7 parts of FeS04.7H20 were then charged batchwise.
It was allowed to react for 2 hours, whereupon the reactor contents were poured onto 150 parts of minced iceO
After extraction with chloroform, the solven-t was distilled and 2.4 parts of starting product were obtained.
Waters were alkalized with 30% NaOH and, after extraction with chloroform, the solvent was distilled, thus obtaining 7.7 parts of N-para-dimethylamino-phenyl-N'-ethyl-urea at a titre of 93.4%. Yield: ahout 69.5%. Melting point =
154-156.5C.
Into a reactor like that of example 1, there were charged: 23.8 parts of a sulphuric solution of N-chloro-piper-idine at 25.2% corresponding to about 6 parts at 100%, 60 parts of concentrated H2SO~
2~L2S
and, keeping the -temperature below 0C, ~.2 parts of N-phenyl-N'-ethyl-urea were added thereto.
7 parts of FeSo~.7H20 were then charged batchwisev It was reacted for 2 hours, whereupon the reactor contents were poured onto 150 parts of minced ice.
After extraction with chloroform, the solvent was distilled and 2.9 parts of starting product were obtained.
8.9 parts of N-para-piperidino-phenyl-N'-ethyl-urea at a titre of 90.2% were obtained. Yield = 65%, melting point = 162.5-164.5C.
Into a reactor like that of example 1, 150 parts of concentrated H2S04 were charged.
ICeeping the temperature below 20C, 19.4 parts of N-4-methoxy-phenyl-N'-ethyl-urea were charged.
Then, under stirring, 37.5 parts of a sulphuric solution of N-chloro-dimethyl-amine at 21.2%, equal to about 8 parts at 100%, were added thereto.
14 parts of FeS04.7 H20 were successively added batchwise.
It was allowed to react for 2 hours, whereupon the reactor contents were poured onto 300 parts of minced ice.
After extraction with chloroform, the solvent was distilled and 1.7 parts of starting product were obtained.
After alkalinization with 30% NaOH, extraction with chloro-form and distillation of the solvent, there were obtained:
22.3 parts of N-3-dimethylamino-4-methoxy-phenyl-N'-ethyl-urea at a titre of 94%.
Yield : about 90%, melting point = 114.5 - 115.5C.
Into a reactor like that of example 1, 60 parts of concentrated H2S03 were charged and, keeping the temperature below 10C, 9 parts of N-4-ethoxy-phenyl-urea were added thereto.
~Z~LZS
Under stirring, there were then char~ed : 40 parts of a sul-phuric solution of N-chloro-dimethyl-amine a-t 9.94%, corres-ponding to about 4 parts at 100C.
6 parts of FeC12 were then charged batchwise.
Following the modalities of exarnple 1, there were obtained :
9 parts of N-3-dimethyl-amino-4-ethoxy-phenyl-urea at 94.7%.
Yield : 76.4%, melting point = 134 - 137C.
Into a reactor like that of e~ample 1, 50 parts of concentrated H2S03 were charged and, keeping the temperature below -5C, 10.4 parts of N-4-ethoxy-phenyl-N',N'-dimethyl-urea were added~ Successively, 4 parts of N-chloro-dimethyl-amine, dissolved in 35 parts of concentrated H2S04, were charged under stirring.
3.5 parts of FeS04.7 H20 were then charged batchwise.
By operating similarly to example 1, it was possible to ob-tain 9.6 parts of N-3-dimethyl amino-4-ethoxy-phenyl N',N'-dimethyl-urea at a titre of 94.4%.
Yield = 72%; melting point = 129 - 131.5C.
By operating analogously with example 3, the following products were prepared :
Ex.No. Acid Catalyst Formula Chromato-mixture graphic analysis , \CH Eluent N
6 96% H2S04 FeS04.7H20 ~ \CH CH / R.F~=0.5 Unitary / N \
H C=0 /N \
~L09Zl~S
/C2H5 R.F.= 0.1 796% H2S04 FeS04^7H2 ~ \C2H5 Unitary ,~N\
H C=0 I~CH2-CH ~ Eluent N.l 896% H2SO4 FeS04O7H20 j C 2 CH~ R F = 0.1 ~N \
H C=0 C2H5 / CH3 R.F.= 0.1 996% H2SO4 FeS04~7~I2 ~ - ~ \ Unitary H C=0 I /CH2-CH2\ Eluent N.l 10 6% 2S04 Fe 4 7 2 ~ ~ CH -CH " 2 Unitary H~N~C o / N \
/ H
\ N/ 2 5 Eluent N.l I R.F.= 0.65 2 44 2 ~ Unitary 9Zl;~5 N-C-N~ Eluent N. 1 ¦ ~CH3 R.F.= 0.65 2 4 4 2 ~ Unitary N _ H
H ~ C-N
~N o \ C H Eluent N.l 13 conc. H2S04 FeS04.7H20 ~ _ CH3 R F = 0.2 CH3 \CH3 H C-N Eluent N. 1 \N/ \C2H5 R F =0 2 14 conc- H2S04 e 4 2 ,N \
C-N
I Eluent N. 2 15 conc. H2S0 = 80 FeS04.7H20 ~ CH3 R F - 0 1 Acetlc acld 20 I CH3 . OCH3 - 18 _ :~0~2~L25 H O H
N-C-N Eluent N. 1 C2H5 R.F.= 002 16 conc. H2S0~ TiC13 ~ Unitary / \ ., All the products were diluted on silicic acid.
Eluent N. 1 : benzene = 79 parts, methanol = 14 parts, acetic acid = 7 parts.
Eluent N.2: toluene = 50 parts, ethyl acetate = 50 parts.
The product of example N. 15 exhibited the same melting point and the same spectra as the one obtained in example N. 3.
The product of example N. 16 exhibited the same melting point and the same spectra as the one obtained in example N. 1.
B) Preparation of amino-carbanylates Into a reactor equipped with stirrer, cooler, thermo-meter and dropping funnel there were charged :
60 parts of concentrated H2S04 and, keeping the temperature below 0C, there were charged-9.75 parts of 4-methoxy-ethyl carbanylate.
Under stirring, the following was then added :
19.1 parts of a sulphuric solution of N-chloro-dimethyl-amine at 20.8%, corresponding to about 4 parts at 100%.
7 parts of FeS04.7H20 were then charged batchwise.
It was allowed to react for 2 hours, whereupon the reactor contents were poured onto 150 parts of minced ice.
After extraction with chloroform, the solvent was distilled and 3.68 parts of unreacted product were obtained.
Waters were alkalized with 30% NaOH and, after extraction with chloroform, the solvent was distilled, thus obtaining 7.26 parts of 3-N,N-dimethyl-amino-4-methoxy ethyl carbanylate ~L~9Z~S
acid at a titre of 90.7%. Yield ~ 95%.
The product eluted on salicylic acid exhibited a R.F. of 0.5 with the eluent consisting of 50 parts of toluene, 50 parts of ethyl acetate, and a R.F. of 0.5 with the eluent consisting of 79 parts of benzene, 14 parts of methanol, 7 parts of acetic acid.
By operating according to example 1, but varying the starting materials, i.e. the type of carbanylate and of chloro-amine, the following products were prepared:
~ . . .... . . . .. . ... .... . __ ___ _ _ .... ._ _ __ Z~ 5 ~1 ,, I . .
o d~ o ~ o ~9 0 ~1 Z
~) O :~ o ~ O
o o ~ ~ a) ~ ~) (I) U
/ O \ / \ /
Z-11_o ~o ~
,~ O O
a u~ u, o ~ a) ~ u~
C) a S~
~D ~D O
X ~ (~
.~ d~ od~ od~
U~
~1 ~ d~
X
Z91~25 u ., ~,u~ ~n O
. ~
o . ~ o 0~1 ~ O ~ >, ~, ~~; ~
~ `~ ~
~n ~`1 /
o \ o o U~ o ~ ~ U~
C~
a~
s~
~ ~D
X S~
.~ o ~ o .,, U~
U ~ o ,~
~o' In X~
_ 22 --~91Zl~S
U
U~
~,-,, ~ . U~ . Ln O ~ .D o , ~ O ~1 ~) o ~ a ~, X ~ ~ ` ~ /
o~
o~ \ o~
x ~ ~ ~ o ~ o o u~
u~
~ a o ~ ~
~ ~D 0 ~D
x ~ ~ ~
d' d' O O O
,~ u~
~ X X
I` 0 .~J~Vf~
u .~ ~ ~ ~
C O ,, ~ o ~ o ~.
U~ .
0 X~m\ ~ =O f) h ~ ~) \ / / ~ \ --C--~ P~
O O O
. ~ U~
a) a . .
.0 ,~
X C~ o ~1 ~ d' O
O ~ ~0 ,~ u~ O ol ~n u~ I
N (\I
a~
~o' O
X~ ~ ~1 o ~:
~U~ . ' . In ~l~rl o ~ o. o ~
o ~ ~ ~, o ~, ~ o ,1 ~ s~
a O ~
~ ~ o ~ C)--O
~ \o (o~ \o~~~ \0-~
~1 ~ ~
~1 ~ O
O o V~
a .,, u~ a U E~
~1 ~ CO ' X C~
.,1 ~ 0~ 0~ 0~
., O
~
o ~ ~ Lr X~ . ~ ~
u r-l r-¦ r-¦
O ~ d' o ~ a) .~ a) ~ ~
U r~ r U ~) t_) r~ ~) U ~ I U U
U
f~
.~
~rl U
rl ~a r~
- rl~J O
ta ~ ~
0~ 0~' ,U~I~
O
'd Ei ~ I I
a) ~ ~ . r-¦ ~ O
I ~ ~ ~ a X
r O O
~ X ~U ~
~ r-¦ ~I
~ ~
a a ~Z r~ r~¦ r-¦
x ~
_ 26 --
For the compounds listed hereinbefore it is understood that the methyl of the ester group can be substituted by an ethyl.
Other employable carbanylates are for exam~le :
_ g _ ~LQ~2~XS
- beta-chloro-ethyl earbanylate - beta-cyano-ethyl carbanylate - propyl earbanylate - isopropyl carbanylate - tert.-butyl earbanylate - eyelohexyl carbanylate - beta-hydroxy-ethyl earbanylate - beta-ehloro-ethyl N-methyl-earbanylate - eyelohexyl N-ethyl-earbanylate - eyclohexyl N-eyelohexyl-carbanylate - beta-eyano-ethyl N-methyl-carbanylate - propyl 4-methoxy-carbanylate - tert.-butyl 4-methoxy-carbanylate - isopropyl N-methyl-4-methoxy-carbanylate - N-cyelohexyl-4-cyclohexyl-oxy-eyelohexyl earbanylate - N-ethyl-4-ethoxy beta eyano-ethyl earbanylate.
The proeess for aminating phenyl~ureas ean be represent-ed as follows:
~ _ e - N ~ \ R
N - I - N
Rl N
wherein :
- R and Rl, like or unlike eaeh other, may be hydrogen or an alkyl, eyeloalkyl, aryl, arylkyl, optionally substituted, - R2 may be hydrogen or an alkyl, eye].oalkyl, aryl, aralkyl, 2~L25 optionally substituted;
- R3 and R4, like or unlike each other, may be alkyl, cyclo-alkyl, aralkyl, optionally substituted and furthermore one of the two, either R3 or R4, may be hydrogen. R3 and R4 may also be the residue of a cyclo, optionally substituted, containing or not containing other hetero-atoms;
- A is a benzene ring either or not containing substituents, with at least a free position.
The substituents of Rl, R2, R3, R4 and A may be, for example, halogen, nitrile, sulphonic, carboxylic groups and esters thereof, amino-hydroxyl, alkyl, alkyl-substituted, alkoxyl, alkoxyl-substituted, acylamino, cycloalkyloxy, ureic groups, etc.' in particular the substituents of the alkyl and alkoxyl groups may be, for example, halogen, hydroxyl, carboxylic, sulphoric groups and esters thereof, a nitrile, an alkoxyl.
When Rl, R2, R3 and R4 mean an alkyl or an alkoxyl, their alkyl chains contain preferably 1 to 5 carbon atoms.
The process for aminating the carbanylates with N-chloro-amines can be represented as follows:
O O R
\ / ~ ~> + Cl - N~ ~0 ,N~
wherein :
Rl, R2 may be, for example, an alkyl or cycloalkyl, an aryl, an aralkyl, optionally substituted;
30 R2 may be also hydrogen, R3, R4 may, for example, an alkyl or cycloalkyl, an aralkyl, optionally substituted, and furthermore one of the two Z~,Z~
may be also hydrogen, R3, R4 may constitute the residue of a cyclo, optionally substituted, either or not containing hetero-atoms;
A is a benzene nucleus, having at least a free position.
The substituents of Rl, R2, R3, R4 and A, may be, for example, halogen, nitrile, sulphonic, carboxylic groups and esters thereof, amino, hydroxyl, alkyl, alkyl-substituted, alkoxyl, alkoxyl-substituted, acylamino, cycloalkyloxy, ureic groups, etc.; furthermore the substituen-ts of the alkyls and alkoxyls may be, for instance, halogen, hydroxyl, carboxylic, sulphonic groups and esters thereof, nitrile, oxygen-alkyl.
When Rl, R2, R3, R~ mean an alkyl or an alkoxyl, their alkyl chains contain preferably from 1 to 5 carbon atoms.
In accordance with the process of this invention when a substituted benzene reactant is a phenyl urea type, such as:
N-phenyl-urea ; N-phenyl-N'-ethyl-urea N-methyl-N-phenyl-N',N'-dimethyl-urea N-methyl-N-phenyl-N'-ethyl-urea a selective linking in para position in respect of nitrogen in A is obtained.
If phenyl is substituted in para position, i.e. if products of the following type are used:
N-4-methoxy-phenyl-urea N-4-methoxy-phenyl-N'-ethyl-urea N-4-ethoxy-phenyl-N'-ethyl-urea N-4-hydroxy-phenyl-urea N-4-cyclohexoxy-phenyl-N',N'-dimethyl-urea N-methyl-N-4-chloro-phenyl-urea N-4-ethoxy-phenyl-N',N'-dimethyl-urea a selective linking in meta position in respect of N in A is obtained.
~0~2~S
Conversely, if phenyl is substi-tuted in ortho position, i.e. if products of the following -type are used:
N-2-methyl-phenyl-urea N-2-methyl-phenyl-N',N'-dimethyl-urea N-2-chloro-phenyl-N'-ethyl-urea ~-methyl-N-2-bromo-phenyl-urea, etc.
a selective linking in para position in respect o nitrogen in A is obtained.
As to the carbanylates, when starting products such as:
methyl carbanylate ethyl carbanylate N-methyl-ethyl carbanylate N-ethyl-methyl carbanylate are used, a selective linking in para position in respect of nitrogen in A is obtained.
If phenyl is substituted in para position, i.e. if products of the following type are utilized:
4-methoxy-methyl carbanylate ~ 4-ethoxy-methyl carbanylate 4-methoxy-ethyl carbanylate 4-ethoxy-ethyl carbanylate N-methyl-4-methoxy-methyl carbanylate, a selective linking in meta position in respect of nitrogen in A is obtained.
Conversely, if phenyl is substituted in ortho position, i.e. if products such as the following ones are used:
2-methyl-methyl carbanylatc 2-chloro-ethyl carbanylate 2-methyl-ethyl carbanylate a selective linking in para position in respect of nitrogen in A is obtained.
The following examples are given merely to illustrate 1~1392~Z5 the present invention and are not intended to limit more general aspects thereof.
In such examples, unless otherwise specified, the term "parts"
is to be understood as expressed in units by weight.
For the examples relating to phenyl-ureas, the yield is cal-culated on the amount of N-chloro-amine used, while for the examples concerning the carbanylates, the yield is calculated on the amount of converted carbanylate.
A) Preparation of amino-phenyl-ureas Into a reactor equipped with stirrer, cooler, thermo-meter and dropping funnel, 60 parts of concentrated H2S04 were charged and, keeping the temperature below 10C, 8.2 parts of N-phenyl-N'-ethyl-urea were charged.
Successively, under stirring, there were added thereto 41.7 parts of a sulphuric solution of N-chloro-dimethyl-amine at 9.65%, corresponding to 4 parts at 100%.
7 parts of FeS04.7H20 were then charged batchwise.
It was allowed to react for 2 hours, whereupon the reactor contents were poured onto 150 parts of minced iceO
After extraction with chloroform, the solven-t was distilled and 2.4 parts of starting product were obtained.
Waters were alkalized with 30% NaOH and, after extraction with chloroform, the solvent was distilled, thus obtaining 7.7 parts of N-para-dimethylamino-phenyl-N'-ethyl-urea at a titre of 93.4%. Yield: ahout 69.5%. Melting point =
154-156.5C.
Into a reactor like that of example 1, there were charged: 23.8 parts of a sulphuric solution of N-chloro-piper-idine at 25.2% corresponding to about 6 parts at 100%, 60 parts of concentrated H2SO~
2~L2S
and, keeping the -temperature below 0C, ~.2 parts of N-phenyl-N'-ethyl-urea were added thereto.
7 parts of FeSo~.7H20 were then charged batchwisev It was reacted for 2 hours, whereupon the reactor contents were poured onto 150 parts of minced ice.
After extraction with chloroform, the solvent was distilled and 2.9 parts of starting product were obtained.
8.9 parts of N-para-piperidino-phenyl-N'-ethyl-urea at a titre of 90.2% were obtained. Yield = 65%, melting point = 162.5-164.5C.
Into a reactor like that of example 1, 150 parts of concentrated H2S04 were charged.
ICeeping the temperature below 20C, 19.4 parts of N-4-methoxy-phenyl-N'-ethyl-urea were charged.
Then, under stirring, 37.5 parts of a sulphuric solution of N-chloro-dimethyl-amine at 21.2%, equal to about 8 parts at 100%, were added thereto.
14 parts of FeS04.7 H20 were successively added batchwise.
It was allowed to react for 2 hours, whereupon the reactor contents were poured onto 300 parts of minced ice.
After extraction with chloroform, the solvent was distilled and 1.7 parts of starting product were obtained.
After alkalinization with 30% NaOH, extraction with chloro-form and distillation of the solvent, there were obtained:
22.3 parts of N-3-dimethylamino-4-methoxy-phenyl-N'-ethyl-urea at a titre of 94%.
Yield : about 90%, melting point = 114.5 - 115.5C.
Into a reactor like that of example 1, 60 parts of concentrated H2S03 were charged and, keeping the temperature below 10C, 9 parts of N-4-ethoxy-phenyl-urea were added thereto.
~Z~LZS
Under stirring, there were then char~ed : 40 parts of a sul-phuric solution of N-chloro-dimethyl-amine a-t 9.94%, corres-ponding to about 4 parts at 100C.
6 parts of FeC12 were then charged batchwise.
Following the modalities of exarnple 1, there were obtained :
9 parts of N-3-dimethyl-amino-4-ethoxy-phenyl-urea at 94.7%.
Yield : 76.4%, melting point = 134 - 137C.
Into a reactor like that of e~ample 1, 50 parts of concentrated H2S03 were charged and, keeping the temperature below -5C, 10.4 parts of N-4-ethoxy-phenyl-N',N'-dimethyl-urea were added~ Successively, 4 parts of N-chloro-dimethyl-amine, dissolved in 35 parts of concentrated H2S04, were charged under stirring.
3.5 parts of FeS04.7 H20 were then charged batchwise.
By operating similarly to example 1, it was possible to ob-tain 9.6 parts of N-3-dimethyl amino-4-ethoxy-phenyl N',N'-dimethyl-urea at a titre of 94.4%.
Yield = 72%; melting point = 129 - 131.5C.
By operating analogously with example 3, the following products were prepared :
Ex.No. Acid Catalyst Formula Chromato-mixture graphic analysis , \CH Eluent N
6 96% H2S04 FeS04.7H20 ~ \CH CH / R.F~=0.5 Unitary / N \
H C=0 /N \
~L09Zl~S
/C2H5 R.F.= 0.1 796% H2S04 FeS04^7H2 ~ \C2H5 Unitary ,~N\
H C=0 I~CH2-CH ~ Eluent N.l 896% H2SO4 FeS04O7H20 j C 2 CH~ R F = 0.1 ~N \
H C=0 C2H5 / CH3 R.F.= 0.1 996% H2SO4 FeS04~7~I2 ~ - ~ \ Unitary H C=0 I /CH2-CH2\ Eluent N.l 10 6% 2S04 Fe 4 7 2 ~ ~ CH -CH " 2 Unitary H~N~C o / N \
/ H
\ N/ 2 5 Eluent N.l I R.F.= 0.65 2 44 2 ~ Unitary 9Zl;~5 N-C-N~ Eluent N. 1 ¦ ~CH3 R.F.= 0.65 2 4 4 2 ~ Unitary N _ H
H ~ C-N
~N o \ C H Eluent N.l 13 conc. H2S04 FeS04.7H20 ~ _ CH3 R F = 0.2 CH3 \CH3 H C-N Eluent N. 1 \N/ \C2H5 R F =0 2 14 conc- H2S04 e 4 2 ,N \
C-N
I Eluent N. 2 15 conc. H2S0 = 80 FeS04.7H20 ~ CH3 R F - 0 1 Acetlc acld 20 I CH3 . OCH3 - 18 _ :~0~2~L25 H O H
N-C-N Eluent N. 1 C2H5 R.F.= 002 16 conc. H2S0~ TiC13 ~ Unitary / \ ., All the products were diluted on silicic acid.
Eluent N. 1 : benzene = 79 parts, methanol = 14 parts, acetic acid = 7 parts.
Eluent N.2: toluene = 50 parts, ethyl acetate = 50 parts.
The product of example N. 15 exhibited the same melting point and the same spectra as the one obtained in example N. 3.
The product of example N. 16 exhibited the same melting point and the same spectra as the one obtained in example N. 1.
B) Preparation of amino-carbanylates Into a reactor equipped with stirrer, cooler, thermo-meter and dropping funnel there were charged :
60 parts of concentrated H2S04 and, keeping the temperature below 0C, there were charged-9.75 parts of 4-methoxy-ethyl carbanylate.
Under stirring, the following was then added :
19.1 parts of a sulphuric solution of N-chloro-dimethyl-amine at 20.8%, corresponding to about 4 parts at 100%.
7 parts of FeS04.7H20 were then charged batchwise.
It was allowed to react for 2 hours, whereupon the reactor contents were poured onto 150 parts of minced ice.
After extraction with chloroform, the solvent was distilled and 3.68 parts of unreacted product were obtained.
Waters were alkalized with 30% NaOH and, after extraction with chloroform, the solvent was distilled, thus obtaining 7.26 parts of 3-N,N-dimethyl-amino-4-methoxy ethyl carbanylate ~L~9Z~S
acid at a titre of 90.7%. Yield ~ 95%.
The product eluted on salicylic acid exhibited a R.F. of 0.5 with the eluent consisting of 50 parts of toluene, 50 parts of ethyl acetate, and a R.F. of 0.5 with the eluent consisting of 79 parts of benzene, 14 parts of methanol, 7 parts of acetic acid.
By operating according to example 1, but varying the starting materials, i.e. the type of carbanylate and of chloro-amine, the following products were prepared:
~ . . .... . . . .. . ... .... . __ ___ _ _ .... ._ _ __ Z~ 5 ~1 ,, I . .
o d~ o ~ o ~9 0 ~1 Z
~) O :~ o ~ O
o o ~ ~ a) ~ ~) (I) U
/ O \ / \ /
Z-11_o ~o ~
,~ O O
a u~ u, o ~ a) ~ u~
C) a S~
~D ~D O
X ~ (~
.~ d~ od~ od~
U~
~1 ~ d~
X
Z91~25 u ., ~,u~ ~n O
. ~
o . ~ o 0~1 ~ O ~ >, ~, ~~; ~
~ `~ ~
~n ~`1 /
o \ o o U~ o ~ ~ U~
C~
a~
s~
~ ~D
X S~
.~ o ~ o .,, U~
U ~ o ,~
~o' In X~
_ 22 --~91Zl~S
U
U~
~,-,, ~ . U~ . Ln O ~ .D o , ~ O ~1 ~) o ~ a ~, X ~ ~ ` ~ /
o~
o~ \ o~
x ~ ~ ~ o ~ o o u~
u~
~ a o ~ ~
~ ~D 0 ~D
x ~ ~ ~
d' d' O O O
,~ u~
~ X X
I` 0 .~J~Vf~
u .~ ~ ~ ~
C O ,, ~ o ~ o ~.
U~ .
0 X~m\ ~ =O f) h ~ ~) \ / / ~ \ --C--~ P~
O O O
. ~ U~
a) a . .
.0 ,~
X C~ o ~1 ~ d' O
O ~ ~0 ,~ u~ O ol ~n u~ I
N (\I
a~
~o' O
X~ ~ ~1 o ~:
~U~ . ' . In ~l~rl o ~ o. o ~
o ~ ~ ~, o ~, ~ o ,1 ~ s~
a O ~
~ ~ o ~ C)--O
~ \o (o~ \o~~~ \0-~
~1 ~ ~
~1 ~ O
O o V~
a .,, u~ a U E~
~1 ~ CO ' X C~
.,1 ~ 0~ 0~ 0~
., O
~
o ~ ~ Lr X~ . ~ ~
u r-l r-¦ r-¦
O ~ d' o ~ a) .~ a) ~ ~
U r~ r U ~) t_) r~ ~) U ~ I U U
U
f~
.~
~rl U
rl ~a r~
- rl~J O
ta ~ ~
0~ 0~' ,U~I~
O
'd Ei ~ I I
a) ~ ~ . r-¦ ~ O
I ~ ~ ~ a X
r O O
~ X ~U ~
~ r-¦ ~I
~ ~
a a ~Z r~ r~¦ r-¦
x ~
_ 26 --
Claims (12)
1. Process for preparing aminophenyl-ureas and amino-carbanylates by direct amination of phenylureas and carbanylates respectively by means of N-chloro-amines, in a redox type system, in an acid reaction medium.
2. Process according to claim 1, characterized in that there are employed N-chloro-amines having general formula:
wherein:
R3 may be an alkyl, cycloalkyl, aralkyl;
R4 may be hydrogen or an alkyl, cycloalkyl, aralkyl;
R3,R4 may also form with N a piperidine ring.
wherein:
R3 may be an alkyl, cycloalkyl, aralkyl;
R4 may be hydrogen or an alkyl, cycloalkyl, aralkyl;
R3,R4 may also form with N a piperidine ring.
3. Process according to claim 1, characterized in that the phenyl-ureas employed have the general formula:
wherein:
R, R1, either like or unlike each other, may be hydrogen or an alkyl, cycloalkyl, aryl, aralkyl;
R2 may be hydrogen or an alkyl, cycloalkyl, aryl, aralkyl;
A is a benzene ring either or not containing substi-tuents, with at least a free position.
wherein:
R, R1, either like or unlike each other, may be hydrogen or an alkyl, cycloalkyl, aryl, aralkyl;
R2 may be hydrogen or an alkyl, cycloalkyl, aryl, aralkyl;
A is a benzene ring either or not containing substi-tuents, with at least a free position.
4. Process according to claim 1, characterized in that aminophenyl-ureas having the following general formula are obtained:
wherein:
R, R1, R2, R3, R4 and A have the meanings defined in claims 2 and 3 hereinbefore.
wherein:
R, R1, R2, R3, R4 and A have the meanings defined in claims 2 and 3 hereinbefore.
5. Process according to claim 1, characterized in that the carbanylates employed have the following general formula:
wherein:
R1 may be an alkyl, cycloalkyl, aryl, aralkyl;
R2 may be hydrogen, or an alkyl, cycloalkyl, aryl, aralkyl;
A is a benzene nucleus having at least a free position and where the substituents present on R1, R2 and A
are selected from amongst the halogen, nitrile, sul-phonic groups and esters thereof, the carboxylic group and esters thereof, the amino, hydroxyl, alkoxyl, alkoxyl-substituted, alkyl, alkyl-substituted, acylamino, ureic, cycloalkyloxy groups.
wherein:
R1 may be an alkyl, cycloalkyl, aryl, aralkyl;
R2 may be hydrogen, or an alkyl, cycloalkyl, aryl, aralkyl;
A is a benzene nucleus having at least a free position and where the substituents present on R1, R2 and A
are selected from amongst the halogen, nitrile, sul-phonic groups and esters thereof, the carboxylic group and esters thereof, the amino, hydroxyl, alkoxyl, alkoxyl-substituted, alkyl, alkyl-substituted, acylamino, ureic, cycloalkyloxy groups.
6. Process according to claim 1, characterized in that the amino-carbanylates having the following general formula are obtained:
wherein :
R1, R2, R3, R4 have the same meanings as defined in claims 2 and 5 hereinbefore.
wherein :
R1, R2, R3, R4 have the same meanings as defined in claims 2 and 5 hereinbefore.
7. Process according to claim 1, characterized in that the reaction medium contains a strong acid selected from the group consisting of sulphuric acid, trifluoroacetic acid and mixtures thereof with acetic acid, and a salt selected from the group consisting of ferrous, cuprous and titanous salts.
8. Process according to claim 7, characterized in that the acid reaction medium contains ferrous sulphate.
9. Process according to claim 7, characterized in that the acid reaction medium contains concentrated H2S04 or mixtures thereof with solvents, in which H2S04 is employed at a concentration by weight equal to at least 25%.
10. Process according to claim 1, characterized in that N-chloro-amine is employed in molar ratios comprised between 1:3 and 3:1 in respect of phenyl-urea.
11. Process according to claim 8, characterized in that ferrous sulphate is employed in molar ratios comprised between 1:1 and 1:100 in respect of N-chloro-amine.
12. Process according to claim 11, characterized in that ferrous sulphate is employed in molar ratios comprised between 1:1.2 and 1:50 in respect of N-chloro-amine.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT1909377A IT1076004B (en) | 1977-01-07 | 1977-01-07 | Substd. aminobenzene deriv. prepn. by direct amination - of benzene deriv. with N-chloro-amine(s) using redox system in strong acid medium, esp. for phenylurea and carbanilate derivs. |
| IT19093A/77 | 1977-01-07 | ||
| IT20262A/77 | 1977-02-14 | ||
| IT2026277A IT1075118B (en) | 1977-02-14 | 1977-02-14 | Substd. aminobenzene deriv. prepn. by direct amination - of benzene deriv. with N-chloro-amine(s) using redox system in strong acid medium, esp. for phenylurea and carbanilate derivs. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1092125A true CA1092125A (en) | 1980-12-23 |
Family
ID=26327047
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA294,489A Expired CA1092125A (en) | 1977-01-07 | 1978-01-06 | Process for preparing amino-phenyl-ureas and amino- carbanylates |
Country Status (6)
| Country | Link |
|---|---|
| JP (1) | JPS53124237A (en) |
| CA (1) | CA1092125A (en) |
| DE (1) | DE2800111A1 (en) |
| FR (1) | FR2376841A1 (en) |
| GB (1) | GB1554543A (en) |
| NL (1) | NL7800026A (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1067024B (en) * | 1976-11-17 | 1985-03-12 | Acna | PROCEDURE FOR THE PREPARATION OF AROMATIC AMINES |
| OA07768A (en) * | 1983-05-12 | 1985-08-30 | Sumitomo Chemical Co | Derivatives of fungicidal anillins. |
| SE9802209D0 (en) * | 1998-06-22 | 1998-06-22 | Astra Pharma Inc | Novel compounds |
| CA2413421A1 (en) * | 2000-06-21 | 2001-12-27 | Bristol-Myers Squibb Pharma Company | N-ureidoalkyl-piperidines as modulators of chemokine receptor activity |
| AU2005260495B2 (en) * | 2004-07-02 | 2009-04-30 | Sankyo Company, Limited | Urea derivative |
| EP2256105B1 (en) | 2008-03-26 | 2013-12-04 | Daiichi Sankyo Company, Limited | Novel tetrahydroisoquinoline derivative |
-
1978
- 1978-01-02 NL NL7800026A patent/NL7800026A/en not_active Application Discontinuation
- 1978-01-03 DE DE19782800111 patent/DE2800111A1/en not_active Withdrawn
- 1978-01-04 GB GB16178A patent/GB1554543A/en not_active Expired
- 1978-01-04 FR FR7800113A patent/FR2376841A1/en active Granted
- 1978-01-06 JP JP29078A patent/JPS53124237A/en active Pending
- 1978-01-06 CA CA294,489A patent/CA1092125A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| FR2376841A1 (en) | 1978-08-04 |
| JPS53124237A (en) | 1978-10-30 |
| DE2800111A1 (en) | 1978-07-13 |
| FR2376841B1 (en) | 1981-10-09 |
| NL7800026A (en) | 1978-07-11 |
| GB1554543A (en) | 1979-10-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US2655534A (en) | Preparation of n-aromatic-n'-aliphatic hydrocarbon ureas | |
| CA1092125A (en) | Process for preparing amino-phenyl-ureas and amino- carbanylates | |
| JPH03173860A (en) | Preparation of pure urea disubstituted unsymmetrically | |
| US3746760A (en) | N-monohalomonosubstituted ureas | |
| PL117490B1 (en) | Method for manufacturing thiocarbamates | |
| JPS6222730A (en) | Manufacture of carboxylic acid chloride and catalyst therefor | |
| JPS61238750A (en) | Manufacture of alkoxyhalides | |
| US3657324A (en) | Hydrazine derivatives and process therefor | |
| US2753345A (en) | Substituted mercaptobenzoic acids and methods of preparing the same | |
| CA1209589A (en) | Process for the preparation of optionally halogenated anilines | |
| US3118903A (en) | 2-oxo-1, 2, 3, 5-oxathiadiazoles and methods for preparing the same | |
| US3059029A (en) | Process for alkyl and aralkyl biguanides | |
| IL27897A (en) | Preparation of pyrazinoylguanidines and pyrazinamidoguanidines | |
| DE3880997T2 (en) | METHOD FOR ALLYLATING PERHALOALKYL, PERHALOALKOXY, PERHALOALKYLTHIOANILINES IN THE PRESENCE OF METALS. | |
| US3163667A (en) | Preparation of beta-sulfato-ethane sulfonamides and amine salts thereof | |
| CA1092124A (en) | Process for the preparation of aromatic amines | |
| US2709706A (en) | Preparation of beta-dithiocarbamyl and beta-mercapto carboxylic acid amides and the corresponding hydrazides | |
| US3340254A (en) | Amino methylene ureas | |
| US3644518A (en) | Process for the production of naphthamide derivatives | |
| US3159663A (en) | Process for preparing amino-substituted sulfate esters | |
| US2014522A (en) | Manufacture of azoxy-arylamines | |
| US4081436A (en) | Process for dry quaternization of azo compounds | |
| US2655528A (en) | Sulfur trioxide compounds of pentaalkylguanidines | |
| US2836602A (en) | Process for the production of z-amino-s- | |
| US2377485A (en) | Process for the production of sulphonylguanidines |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |