DE1670918A1 - Process for the preparation of 2-aryl-amino-substituted nitrogen-containing heterocycles - Google Patents

Description

Process for the preparation of 2-arylamino-substituted nitrogen-containing Heterocycles It has been found that 2-arylamino-substituted nitrogen-containing Heterocycles are obtained if diamines of the general formula R1NH- (CnH2n-2 R2R3) -NHR4 in which n is the number 2 or 3 and in which R1 and R4 are identical or different radicals such as hydrogen, an alkyl or cycloalkyl radical, and where R1 furthermore denotes an optionally substituted aryl radical, and where R2 and R3 are hydrogen and one of the radicals R2 and R3 is the same or the same different radicals such as hydrogen or one optionally by a lower one Alkoxy radical means substituted aliphatic radical, and where one of the radicals R2 or R3 represents an optionally substituted aryl or aralkyl radical, with about the stoichiometrically required amount of a carbodiimide of the general Formula R5-N = C = N-R6 in which R5 and R6 represent the same or different given values substituted aryl radicals, preferably in Presence of one inert organic solvent in the temperature range from about 20 to about 150 ° C, preferably about 70 to about 100 ° C., and optionally after removal of the solvent, the guanidine derivative formed, optionally without intermediate isolation and optionally in the presence of a high-boiling inert organic solvent heated to about 100 to about 250 ° C, optionally under reduced pressure, and after the amine split off and, if appropriate, the solvent present have been distilled off the heterocyclic compound formed is isolated.

As aliphatic radicals (R1, R4), alkyl creations with 1-20 are preferred 1-6 carbon atoms, as cycloaliphatic radicals those with 5-12, preferably Mentioned 5 or 6 carbon atoms in the ring system. Aromatic radicals (R1) are such with up to 10 carbon atoms in the ring system, preferably the phenyl radical. the aromatic ring systems (phenyl, amphtyl) can optionally also be replaced by halogens (preferably fluorine, chlorine, bromine) alkoxy or S-alkyl with 1 to 12 each, preferably 1-4 carbon atoms, straight-chain or branched alkyl radicals with up to 12, preferably 1-4 carbon atoms, 5- or 6-membered cycloalkyl radicals (optionally through lower alkyl groups substituted), dialkylamino groups (with 1-6 carbon atoms per alkyl group) where the alkyl radicals together also components of one 5- or 6-membered ring system can be substituted.

As optionally by lower alkoxy groups (preferably I-4 carbon atoms) substituted aliphatic radicals are alkyl radicals with 1-20, preferably 1-6 carbon atoms as well as 5- or 6-membered cycloaliphatic radicals. In the event that # R2 or R3 denotes an optionally substituted aryl radical, it is around aromatic radicals with up to 10 carbon atoms in the ring system (preferably Jhenyl but also NaDhtyl), which may be replaced by the at R1 for the aromatic Remainder mentioned atoms or groups can be substituted. Aralkyl radicals are such with 1-4, preferably 1-2 carbon atoms in the aliphatic part, the aromatic The remainder (preferably phenyl but also naphthyl), optionally through halogens, alkoxy or S-alkyl groups may be substituted with the scope given above can.

Optionally substituted aryl radicals (R5 and R) are also to be understood as meaning those with up to 10 carbon atoms in the ring system. The following may be mentioned as substituents of the aromatic radicals R and R6 (preferably phenyl but also naphthyl): halogen (fluorine, chlorine, bromine) alkyl with 1-20, preferably 1-8 carbon atoms, alkoxy and S-alkyl with 1-6 each, preferably 1-4 carbon atoms, 5- and 6-membered cycloalkyl radicals, dialkylamino with 1-4 carbon atoms per alkyl group, wherein these alkyl radicals can furthermore together also be components of a 5- or 6-membered heterocyclic ring system, which in the case of the 6-membered ring optionally as further heteroatom can also contain oxygen or sulfur; further substituents are: phenyl, benzyl, phenoxy, dernc or. B-naphthyl radical as well The amines used for the process according to the invention include, for example: Ethyleneditmin-1,2,1.2-diaminopropane, 1,3-diaminopropane, 1,2-diaminobutane, 1,3-diaminopentane, 2,4-N-phenyl- N "-wethyl-ethylenediamine, N-dodecylphenyl-ethylenediamine, N- (2,4-dicchlorophenyl) -ethylenediamine and the like. Other diarylcarbodiimides used for the process may be mentioned, for example: Diphenylcarbodiimide, di- (ortho-toluyl) -carbodiimide, di- (m-toluyl) -carbodiimide, di- (p-toluyl) -carbodiimide, bis- (2,6-dimethylphenyl) -carbodiimide, bis- (2,4-dimethylphenyl) -carbodiimide, bis- ( 2,5-Dimethyl-phenyl) -carbodiimide, bis- (2-ethylphenyl) -carbodiimide, bis- (4-ethylphenyl) -carbodiimide, bis- (3-ethylphenyl) -carbodiimide, bis- (2-iBopropylphenyl) -carbodiimide , Bia- (2n-propylphenyl) -carbodiimide, bis- (3-normal / iso-propylphenyl) -carbodiimide, bis- (4-normal / iso-propylphelyl) -carbodiimide, Bi8- (2-methyl-6-chlorophenyl) -carbodiimide, bis- (2,6-dichlorophenyl) -carbodiimide, bis- (2,6-dimeth yl-4-chlorophenyl) -carbodiimide, N- (4-chlorophenyl) -N- (2,6-diisopropylphenyl) -carbodiimide, bis- (1,4-diphenyl) -carbodiimide, N-naphthyl-N'-phenylcarbodiimide, N-2,6-diisopropylphenyl-Nt'-4-methylphenylcarbodiimide.

The diarylcarbodiimides used for the process are known or can be obtained by known methods (see e.g. magazine for applied chemistry, 74, pp. 804 and 805 (1962)).

When carrying out the method according to the invention is in the first stage generally in the temperature range from about 120 to about 150 ° C., preferably from about 70 to about 100 ° C, in the second stage in the temperature range of about 100 to about 250 ° C, preferably from about 130 to about 200 ° C worked.

In a two-way manner, the aromatic which is released during the reaction is removed Amine during the implementation. This is advantageously done under reduced pressure, preferably under 100 Torr., worked, naturally taking the negative pressure of the type of the released Arylamine adapts. It may optionally be advantageous to carry out the reaction in the presence of high-boiling, inert, organic solvents such as Xylene, o-dichlorobenzene, 1, 2, 4-trichlorobenzene, tetrahydronaphthalene, decahydronaphthalene, or in mixtures of such solvents. Here ee is often It is advisable to first heat without applying a vacuum and only later that Aromatic amine set free together with the solvent, if appropriate remove at reduced pressure.

The compounds obtainable by the process according to the invention are mostly obtained in good purity and in excellent yields. For special areas of application with the highest purity requirements, they can easily be further purified by recrystallization. The heterocyclic compounds obtainable by the process described are valuable intermediates for further reactions and can be used as lubricant additives. They correspond to the general formula in which the radicals R1 to R5 as well as n have the abovementioned meaning.

Example 1 30 parts by weight of ethylenediamine were in 100 parts of benzene dissolved and treated dropwise at room temperature with 97 parts of diphenylcarbodiimide. After standing for several hours at room temperature, the benzene was distilled off and the residue is heated to 150 ° C. in an oil bath. The 2-phenylimino-imidazolidine solidifies crystalline after cooling.

Yield: 78 parts (97% of theory). After recrystallization from Cyclohexane F.: 131-134 ° C.

Analysis: C9HIIN3 Calculated: C 67, 1% H 6, 83% N 26, 07% mol wt. 161 Found: C 66.6% / H 7.10% N 26.30% molar weight. 155 66.9% Example 2 37 parts 1, 2-Diaminopropane in 50 parts of ligroin is added dropwise to a mixture at room temperature from 200 parts of ligroin and 97 parts of diphenylcarbodiimide. External cooling was used the reaction mixture was kept at room temperature.

The resulting, crude NN'-diphenyl-N "-2-amine-D-propylguanidine precipitates as a viscous, white mass. After the ligroin had been separated off, the mixture was heated to 160.degree and under reduced pressure (reducing from 100 to 15 Torr) 80% of theory (37, 2 parts) aniline distilled off. All that remained was a clear melt solidified at room temperature. This residue was found to be identical by the IR spectrum identified with the 2-phenylimino-4-methyl-imidazolidine from Example 1.

Example 3 1 mol of di-m-toluylcarbodiimide and 1 mol of propylenediamine-1, 2 were as stated in Example 2 to give the N, N'-di-m-toluyl-N "- (2-aminoproyl) -guanidine reacted and this heated under reduced pressure (15 torr) to 170 ° C.-It were 95 g (88.5% of theory) of m-tolnidine were recovered. 2- (m-Toluyl) -imino-4-methyl-imidazolidine. Acidimetric titration revealed a Molecular weight of 192 and asmotic a molecular weight of 194 (calculated 190) found.

Example 4 N, N'-Diphenyl-N "-methyl- (B-methylaminoethyl) -guanidine (made from diphenylcarbodiimide and N, N-dimethyl-ethylenediamine) were under heated to 200 ° C. under reduced pressure (200 torr). After distilling off 95% of the theoretical amount of aniline, the pressure was reduced to 1.6 Torr. It distilled 98% of theory of 2-phenylimino-1,3-dimethyl-imidazolidine at 134-138 ° C / 1.6 Torr liber. Redistillation at 0.7 Torr, boiling point 113 ° C, gave a pure product in 90% yield.

Analysis: CllHl5N3 Calculated: C 69, 8% H 7, 9% N 22, 2% mol wt. 189 Found: C 69, 84% H 8, 1% N 22.0% mol wt. 168/189 Example 5 One by reaction of 1 mole of 1-amino-3-methylaminopropane with 1 mole of di-p-toluylcarbodiimide N, N'-di-ptoluyl -N "- (3-methylaminopropyl) -guanidine (yield 98% of theory) was heated to 150 ° C. in an oil bath for 1 hour. With subsequent Distillation went over 0.87 mol of p-toluidine.

The residue was identified as 2-p-toluylinino-1-methyl-hexahydro-pyrimidine by IR spectrum identified. By acidimetric titration in alcoholic solutions using hydrochloric acid (Indicator: bromophenol blue) a molecular weight of 210 (calculated 203) was found.

Example 6 35 parts of N- (B-aminoethyl) -N ', N "-bis 2- (i-methyl-3-chlorophenyl) -guanidine were heated in an oil bath under reduced pressure to 220 ° C. 14.1 parts were distilled The remaining residue (20 parts = 95% of theory) solidifies in crystalline form and, according to the IR spectrum, is 2- (2'-methyl-6'-chlorophenyl) imidazolidine of the formula With acidimetric titration, a molecular weight of 216 (calculated 209) was found.

The product was purified by recrystallization (gasoline).

Yield: 17 parts = 70% of theory), melting point 180.degree.

The IR spectrum shows characteristic bands at 761, 710 and 1670 cm 1.

The crude guanidine used in Example 6 was prepared by reacting 29.1 part of bis (2-methyl-6-chlorophenyl) -carbodiiaid (F.: 44-46 ° C) prepared with 6 parts of ethylenediamine in 50 parts of benzene at 80 ° C and distilled off the benzene isolates.

Example 7 a) 16.6 parts of 2, 2 ', 6, 6'-tetrachloro-, @lphenylcarbodiimide and 3.0 parts of ethylenediamine were reacted in 20.0 parts of benzene.

The resulting crude aminoguanidine was after distilling off the solvent implemented directly. b) 20.0 parts of the crude N- (B-aminoethyl) -N, N-bis- (2,6-dichlorophenyl) -guanidine were heated to 150 ° C. in an oil bath. Only a few grams of benzene passed over. Under steadily reducing the pressure to 5 Torr, the temperature of the vessel # contents increased up to 250 ° C. 8.0 parts of dichloroaniline were distilled off. The backlog (100% of theory), a red-brown mass, solidifies in crystalline form after cooling. The 2- (2,6-dichlorophenyl) imidazolidine melts after being recrystallized once from i-propanol at 142-144 ° C., yield: 78% of theory.

The compound obtained was confirmed by IR spectrum and high melting point identified with an authentic sample.

Claims (1)

Claim: Process for the preparation of 2-arylamino-substituted nitrogen-containing heterocycles, characterized in that one diamines of the general Formula R-NH- (CHRR) -NHR in which n is the number 2 or 3 and in which R1 and R4 stands for identical or different radicals such as hydrogen, an alkyl or cycloalkyl radical stand, and where R1 furthermore denotes an optionally substituted aryl radical, and where R2 and R3 denote hydrogen and furthermore ener of the radicals R2 and R3 identical or different radicals such as hydrogen or one optionally through is a lower alkoxy substituted aliphatic radical, and wherein one of the radicals R or R for an optionally substituted aryl or aralkyl radical stands, with about the stoichiometrically required amount of a carbodiimide of general formula R5-N = C = NR6 in which R5 and R6 are optionally identical or different substituted aryl radicals, preferably in the presence of an inert organic Reacts solvent in the temperature range from about 20 to about 150 ° C and optionally after removal of the solvent, the guanidine derivative formed, if appropriate without intermediate isolation and optionally in the presence of a high-boiling inert organic Solvent to about 100 to about 250 ° C, optionally under reduced pressure, heated and after distilling off the cleaved amine and, if appropriate, of the solvent present, the heterocyclic one formed Connection isolated.