EP0005475B1 - Process for the preparation of 4,4'-diaminobenzhydrol and its substitution products - Google Patents

Description

worin

• A und B unabhängig voneinander für einen gegebenenfalls substituierten 1,4-Arylenrest und
• R₁, R₂,
• R₃ und R₄ unabhängig voneinander für Wasserstoff oder einen gegebenenfalls substituierten Alkyl-, Cycloalkyl-, Aralkyl- oder Arylrest stehen, oder
• R₁ und R₂
• bzw.
• R₃ und R₄ gemeinsam mit dem benachbarten Stickstoffatom einen heterocyclischen Ring bilden, oder
  einer oder mehrere der Reste R_i, R₂, R₃ und R₄ mit dem benachbarten Stickstoff und einem benachbarten Kohlenstoffatom des Restes A bzw. B einen heterocyclischen Ring bilden,

durch Reduktion von 4,4'-Benzophenonen der allgemeinen Formel

in einem organischen Lösungsmittel mit Hilfe von Alkaliborhydrid in Gegenwart von einem Alkalimetallhydroxyd.The invention relates to a process for the preparation of 4,4'-diaminobenzhydroles of the general formula

wherein

• A and B independently of one another for an optionally substituted 1,4-arylene radical and
• R ₁ , R ₂ ,
• R ₃ and R ₄ independently of one another represent hydrogen or an optionally substituted alkyl, cycloalkyl, aralkyl or aryl radical, or
• R ₁ and R ₂
• respectively.
• R ₃ and R ₄ together with the adjacent nitrogen atom form a heterocyclic ring, or
  one or more of the radicals R _i , R ₂ , R ₃ and R ₄ form a heterocyclic ring with the adjacent nitrogen and an adjacent carbon atom of the radicals A and B,

by reduction of 4,4'-benzophenones of the general formula

in an organic solvent using alkali borohydride in the presence of an alkali metal hydroxide.

The alkyl radicals mentioned in the formulas (I) and (11) are generally those having 1 -6 carbon atoms.

Particularly suitable substituents of the alkyl radicals are, for example, halogen, hydroxy, C ₁ -C ₄ alkoxy or cyano.

Aryl is preferably understood to mean phenyl or 1- or 2-naphthyl and aralkyl is benzyl and β-phenyl-C ₁ -C ₄ -alkyl. The phenyl rings may, for example, by 1-4 radicals such as halo, C _l -C ₄ alkyl, hydroxy, C _l -C ₄ alkoxy, C _l -C ₄ alkoxycarbonyl, carboxyl, amidocarbonyl, cyano, nitro, amidosulfonyl, C ₁ - C ₃ alkylcarbonylamino or benzoylamino substituted.

Cycloalkyl stands in particular for cyclopentyl and cyclohexyl which, for. B. by 1 -4 radicals, especially methyl, may be substituted.

Examples of heterocyclic rings which are formed by R ₁ and R ₂ or by R ₃ and R ₄ with the adjacent nitrogen atom are the piperidine, N-methylpiperazine and the morpholine ring. Examples of heterocyclic rings which are formed by R ₁ and / or R _{2 being} attached to the aromatic radical A or by R ₃ and / or R _{4 being} attached to the aromatic radical B are julolidine, lilolidine, N- Methyltetrahydroquinoline and 1,2-dimethylindoline called.

A and B preferably represent a 1,4-phenylene or 1,4-naphthylene radical. These radicals can carry 1 -4 substituents such as C ₁ - C ₄ alkyl substituted, C ₁ -C ₄ alkoxy or halogen.

Halogen is understood to mean in particular fluorine, chlorine and bromine.

Alkali borohydrides are preferably understood to mean sodium, potassium and lithium borohydride.

in welcher

• Rs, R₆,
• R₇ und R₈ unabhängig voneinander für Wasserstoff oder einen Alkylrest mit 1 -4 Kohlenstoffatomen stehen, und
• R₉ und R_io unabhängig voneinander Wasserstoff, Methyl, Äthyl, Methoxy, Äthoxy, Chlor oder Brom bedeuten,

mit Natriumborhydrid in einem organischen Lösungsmittel und in Gegenwart von einem Metallhydroxid reduziert.A preferred procedure consists in that diaminobenzophenones of the general formula

in which

• Rs, R ₆ ,
• R ₇ and R ₈ independently of one another represent hydrogen or an alkyl radical having 1 -4 carbon atoms, and
• R ₉ and R _io independently of one another denote hydrogen, methyl, ethyl, methoxy, ethoxy, chlorine or bromine,

reduced with sodium borohydride in an organic solvent and in the presence of a metal hydroxide.

The process is particularly suitable for producing Michler's hydrol (4,4'-tetramethyldiamino-benzhydrol) from Michler's ketone (4,4'-tetramethyldiamino-benzophenone).

The alkali metal hydroxide preferably used in the process according to the invention is potassium hydroxide.

Suitable solvents are monohydric and polyhydric alcohols and their ethers, for example methanol, ethanol, isopropanol, methyl glycol, ethyl glycol, butyl glycol, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether; Dioxane, tetrahydrofuran and acetonitrile are also suitable as solvents.

• 4,4'-Diaminobenzophenon,
• 4,4'-Tetramethyldiaminobenzophenon,
• 4,4'-Tetraäthyldiaminobenzophenon,
• 4,4 -Tetramethyldiamino-2,2'-dimethoxybenzophenon,
• 4,4'-Tetramethyldiamino-2,2'-dimethylbenzophenon,
• 4,4'-Bisbenzylmethylaminobenzophenon,
• 4,4'-Bis-benzyläthylaminobenzophenon,
• 4,4'-Bisdibenzylaminobenzophenon,
• 4,4'-Bisphenylmethylaminobenzophenon,
• 4,4'-Bisphenyläthylaminobenzophenon,
• 4,4'-Bispiperidinobenzophenon,
• 4,4'-Bismorpholinobenzophenon,
• 4,4'-Bis-N-methylpiperazinobenzophenon,
• Bis-(N-methyl-6-tetrahydrochinolyl)-keton.

Suitable starting materials of the general formula (II) are

• 4,4'-diaminobenzophenone,
• 4,4'-tetramethyldiaminobenzophenone,
• 4,4'-tetraethyldiaminobenzophenone,
• 4,4-tetramethyldiamino-2,2'-dimethoxybenzophenone,
• 4,4'-tetramethyldiamino-2,2'-dimethylbenzophenone,
• 4,4'-bisbenzylmethylaminobenzophenone,
• 4,4'-bis-benzylethylaminobenzophenone,
• 4,4'-bisdibenzylaminobenzophenone,
• 4,4'-bisphenylmethylaminobenzophenone,
• 4,4'-bisphenylethylaminobenzophenone,
• 4,4'-bispiperidinobenzophenone,
• 4,4'-bismorpholinobenzophenone,
• 4,4'-bis-N-methylpiperazinobenzophenone,
• Bis (N-methyl-6-tetrahydroquinolyl) ketone.

The reaction can be carried out at a temperature of 20-100 ° C. The preferred temperature range is 50 - 70 ° C.

The solutions of the diaminobenzhydrols obtained in reduction in organic solvents preferably contain 15-35% of the benzhydrols.

It is already known to produce diaminobenzhydrols, such as Michler's hydrol, by oxidizing the corresponding diaminodiarylmethane with lead dioxide or manganese dioxide. Compared to these processes, the process according to the invention has the advantage that it delivers much purer end products. It is also known to prepare diaminobenzhydrols by reducing the corresponding ketones with the aid of zinc dust and an alkali metal hydroxide in a lower alcohol. The advantage over this. The process consists in the fact that no waste water containing heavy metals has to be worked up and that no heavy metal residues have to be separated off.

From FR-A 2179 493 it is known to reduce o-aminobenzophenone with potassium borohydride in the absence of alkali to o-aminobenzohydrol. It was found that p, p'-diaminobenzophenone can only be reduced with a low yield by this process, while the hydrol is surprisingly obtained in excellent yield and purity by the process according to the invention in the presence of alkali metal hydroxide.

The diaminobihydroles which can be prepared according to the invention are suitable as intermediates for the preparation of basic and acidic di- and triaminotriphenylmethane dyes. They are also suitable as intermediates for the production of printing copy dyes, such as crystal violet lactone, leukauramines and sulfinates of diaminobenzhydrols.

example 1

536 g of Michler's ketone (4,4'-tetramethyldiaminobenzophenone) are dissolved with 10 g of KOH in 1500 ml of alcohol while warming to 50 ° C. 40 g of sodium borohydride are added to the solution, the mixture is heated to 70 ° C. and left to stir at this temperature for 3 hours; then another 40 g of sodium borohydride are added, the mixture is stirred for another 3 hours at 70 ° C. and another 20 g of sodium borohydride are added. After stirring at 70 ° C. for 18 hours, the reaction mixture is diluted by adding 21 Water to a volume of 3700 ml, stirring again for 4 hours, suctioned off the separated Michlers hydrol (4,4'- _t ramethyldiaminobenzhydrol) and washes it neutral. After drying in vacuo, 506.2 g of Michler's hydrol are obtained. Melting point 101 -103 ° C. The same volume of isopropanol can be used instead of alcohol.

Example 2

53.6 g of Michler's ketone are heated to 70 ° C. with 150 ml of ethylene glycol dimethyl ether. A solution of 12 g sodium borohydride and 1 g KOH in 24 ml water is added dropwise evenly within 6 hours. After stirring for 2 hours at 70 ° C, only a trace of the starting material is shown in the thin layer chromatogram. The mixture is diluted with 200 ml of water, the suspension is left to stir at room temperature overnight, and Michler's hydrol is suctioned off and washed neutral.

Yield: 52.6 g, melting point: 104-105 ° C.

If instead of ethylene glycol dimethyl ether the diethylene glycol dimethyl ether is used as the solvent and the procedure is otherwise the same, Michler's hydrol is obtained in a yield of 51.9 g with a melting point of 104-105 ° C. In the same way, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monobutyl ether, dioxane, tetrahydrofuran and acetonitrile can be used as solvents. Equally good results are also obtained with the addition products of methanol, ethanol and diethylene glycol with caprolactam.

Example 3

42.4 g of 4,4'-diaminobenzophenone are heated to 70 ° C. with 150 ml of ethylene glycol dimethyl ether and a solution of 12 g of sodium borohydride and 1 g of KOH in 24 ml of water is added dropwise within 6 hours. The reaction mixture is left to stir at 70 ° C. for a further 18 hours, then only traces of the starting material 4,4'-diaminobenzophenone are shown in the thin-layer chromatogram. A clear solution is formed when diluted with 200 ml of water. The 4,4'-diaminobenzhydrol is salted out by adding 500 ml of saturated saline. After stirring for 3 hours, the hydrol is suctioned off and dried in vacuo. 37.5 g of 4,4'-diaminobenzhydrol are obtained. Melting point after recrystallization from methanol: 113-114 ° C.

Example 4

• 4,4'-Tetrabutyldiaminobenzophenon,
• 4,4'-Tetramethyldiamino-2,2'-dichlorbenzophenon,
• 4,4'-Bis-N-benzylmethylaminobenzophenon,
• 4,4'-Bis-N-benzyläthylaminobenzophenon,
• 4,4'-Bis-N-dibenzytäminobenzophenon,
• 4,4'-Bis-N-phenylmethylaminobanzophenon,
• 4,4'-Bis-N-phenyläthylamino-benzophenon,
• 4,4'-Bispiperidinobenzophenon,
• 4,4'-Bismorpho)inobenzophenon,
• 4,4'-Bis-N-methylpiperazinobenzophenon,
• Bis-(N-methyl-6-tetrahydrochinolyl)-keton.

32.4 g of 4,4'-bisdiethylaminobenzophenone are heated to 50 ° C. with 100 ml of alcohol and 1 g of KOH. Now 2 g of sodium borohydride are added and the suspension is further heated to 70 ° C. After stirring for 3 hours at 70 ° C., 2 g of sodium borohydride are again added, the mixture is heated to 70 ° C. for a further 3 hours and set three times at 3-hour intervals 2 g of sodium borohydride. The reaction mixture is then left to stir at 70 ° C. for a further 20 hours, 400 ml of water are added and the mixture is again stirred at room temperature for 4 hours. The precipitated tetraethyldiaminobenzhydrol is filtered off and washed neutral with water. A yield of 31.2 g is obtained. After recrystallization from methylcyclohexane, the melting point is 74-75 ° C. If one of the compounds listed below is used instead of the 4,4'-tetraethyldiaminobenzophenone used in this example and the procedure is otherwise the same, the corresponding diaminobenzhydrols are obtained in good yield and quality:

• 4,4'-tetrabutyldiaminobenzophenone,
• 4,4'-tetramethyldiamino-2,2'-dichlorobenzophenone,
• 4,4'-bis-N-benzylmethylaminobenzophenone,
• 4,4'-bis-N-benzylethylaminobenzophenone,
• 4,4'-bis-N-dibenzytaminobenzophenone,
• 4,4'-bis-N-phenylmethylaminobanzophenone,
• 4,4'-bis-N-phenylethylamino-benzophenone,
• 4,4'-bispiperidinobenzophenone,
• 4,4'-bismorpho) inobenzophenone,
• 4,4'-bis-N-methylpiperazinobenzophenone,
• Bis (N-methyl-6-tetrahydroquinolyl) ketone.

Claims (3)

1. Process for the preparation of 4,4'-diaminobenzhydrol and its substitution products of the general formula

where in

A and B independently of one another represent an optionally substituted 1,4-arylene radical and

R₁, R₂,

R₃ and R₄ independently of one another represent hydrogen or an optionally substituted alkyl, cycloalkyl, aralkyl or aryl radical, or

R, and R₂,
and

R₃ and R₄ together with the adjacent nitrogen atom, form a heterocyclic ring, or one or more of the radicals R_i, R₂, R₃ and R₄, with the adjacent nitrogen atom and an adjacent carbon atom of the radical A or B, form a heterocyclic ring,

characterised in that4,4'-diaminobenzophenones of the general formula

are reduced in an organic solvent with the aid of an alkali metal borohydride in the presence of an alkali metal hydroxide.

2. Process according to Claim 1, characterised in that diaminobenzophenones of the general formula

in which

R₅, R₆,

R₇ and R₈ independently of one another represent hydrogen or an alkyl radical with 1 -4 carbon atoms and

R₉ and R_io independently of one another denote hydrogen, methyl, ethyl, methoxy, ehoxy, chlorine or bromine,

are reduced with sodium borohydride in an organic solvent and in the presence of a metal hydroxide.

3. Process according to Claim 1, characterised in that 4,4'-tetramethyldiaminobenzophenone or 4,4'-tetraethyldiaminobenzophenone is reduced with sodium borohydride in an organic solvent and in the presence of a metal hydroxide.