DE3832756A1 - METHOD FOR PRODUCING N-ARALKYLATED AMINOFLUORANE COMPOUNDS - Google Patents

Abstract

N-aralkylated and N-aryloxyalkylated aminofluoranes, are prepared by reacting a 2-aminofluorane of formula <IMAGE> wherein the ring A is unsubstituted or substituted by halogen, nitro, amino, C1-5 alkylamino or di-C1-5 alkylamino, R1 and R3 are each independently of the other hydrogen, halogen, C1-5 alkyl or C1-5 alkoxy, R2 is hydrogen, C1-5 alkyl or C1-5 alkoxy, X1 and X2 are each independently of the other hydrogen, alkyl containing not more than 12 carbon atoms which is unsubstituted or substituted by halogen, hydroxy, cyano or C1-5 alkoxy; or are cycloalkyl, tetrahydrofuryl, aryl or acyl, or -NX1X2 is a 5- or 6-membered, preferably saturated, heterocyclic radical, with an aralkylarlsulfonate of formula (2) Z-SO2-O-Y, wherein Z is an aryl radical and Y is an arylalkyl or aryloxyalkyl radical. The N-aryloxyalkylated aminofluorane compounds are also claimed per se

Description

The present invention relates to a method for producing N-aralkylated aminofluorane compounds.

The aralkyl group is usually formed by reacting the amino compound with an aralkyl halide, such as. B. benzyl chloride or benzyl bromide introduced, the implementation in both polar media and in non-polar solvents in the presence of alkali compounds becomes. However, these methods have the disadvantage that polycyclic Amino compounds the end product in some cases inadequate Yield is obtained.

The present invention has for its object an improved To develop a process that promises an increase in yield and at the same time suitable products with high practicality Purity without complicated cleaning steps results.

The present invention therefore relates to a method for Production of N-aralkylated aminofluorane compounds, which thereby is characterized in that a fluorine compound of the formula

in which ring A is unsubstituted or substituted by halogen, nitro, amino, mono-lower alkylamino or di-lower alkylamino,
R₁ and R₃, independently of one another, are each hydrogen, halogen, lower alkyl or lower alkoxy,
R₂ is hydrogen, lower alkyl or lower alkoxy,
X₁ and X₂ independently of one another, each hydrogen, unsubstituted or substituted by halogen, hydroxy, cyano or lower alkoxy alkyl having at most 12 carbon atoms, cycloalkyl, tetrahydrofurfuryl, aryl or acyl or (X₁ and X₂) together with the common nitrogen atom a five- or six-membered, preferably saturated, heterocyclic radical, with an arylsulfonic acid aralkyl ester of the formula

Z-SO₂-O-Y (2)

wherein Z is an aryl radical and
Y represents an arylalkyl or aryloxyalkyl radical.

Halogen means for example fluorine, bromine, iodine or preferably chlorine.

Lower alkyl and lower alkoxy represent in the definition of the residues Fluoranes usually represent such groups or group components that 1 to 5, especially 1 to 3 carbon atoms, such as. B. Methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl or Amyl or methoxy, ethoxy, isopropoxy, tert-butoxy or tert-amyloxy.

"Acyl" is especially formyl, lower alkylcarbonyl, such as. B. acetyl or Propionyl or benzoyl. Other acyl radicals can be lower alkylsulfonyl, such as e.g. B. methylsulfonyl or ethylsulfonyl and phenylsulfonyl. Cycloalkyl means e.g. B. cyclopentyl and especially cyclohexyl. Is aryl especially phenyl or tolyl.

If (X₁ and X₂) together with the common nitrogen atom represent heterocyclic radical, this is for example pyrrolidino, Piperidino, Pipecolino, Morpholino, Thiomorpholino or Piperazino, such as B. Methylpiperazino. Preferred saturated heterocyclic Residues for -NX₁X₂ are pyrrolidino, piperidino or morpholino.

X₁ and X₂ can be the same or different and are is preferably C₁-C₆ alkyl, cyclohexyl, phenyl or tolyl or -NR₁R₂ especially pyrrolidino.  

Ring A is preferably not further substituted. If he has substituents has, it is primarily halogen or di-lower alkylamino substituted.

Particularly good results are obtained in the process according to the invention when using a fluoran compound of the formula given in the R₂ is hydrogen or especially lower alkyl or especially methyl means.

Suitable arylsulfonic acid aralkyl esters of the formula (2) are those in which both the aryl radical Z and the arylalkyl radical or aryloxyalkyl radical Y are unsubstituted or ring-substituted. Preferred Substituents for this are halogens, nitro, trifluoromethyl, lower alkyl, especially methyl or lower alkoxy such as methoxy.

Among these sulfonic acid esters, sulfonic acid esters are particularly suitable of formula (2) in which Y is arylalkyl, such as. B. benzenesulfonates, p-toluenesulfonates, p-bromobenzenesulfonates or p-nitrobenzenesulfonates.

Examples of sulfonic acid esters suitable for introducing the aralkyl group are:
p-toluenesulfonic acid benzyl ester,
Phenyl benzylsulfonate,
p-toluenesulfonic acid phenethyl ester,
p-toluenesulfonic acid phenpropylester,
p-toluenesulfonic acid a -methylbenzyl ester,
Benzenesulfonic acid propyl ester,
p-toluenesulfonic acid phenisopropyl ester,
p-toluenesulfonic acid 4-chlorobenzyl ester,
p-toluenesulfonic acid 4-methylbenzyl ester,
p-toluenesulfonic acid 2,5-dimethyl-benzyl ester,
p-toluenesulfonic acid 2,5-dichlorobenzyl ester,
p-nitrobenzenesulfonic acid benzyl ester,
p-bromobenzenesulfonic acid benzyl ester,
p-toluenesulfonic acid-2,4-dimethyl-benzyl ester,
p-toluenesulfonic acid 4-trifluoromethylbenzyl ester,
p-toluenesulfonic acid 4-methoxybenzyl ester,
p-toluenesulfonic acid 2-phenoxyethyl ester,
2-phenoxyethyl benzenesulfonic acid.

The preferred aryl sulfonic acid is benzyl p-toluenesulfonate. p-Toluenesulfonic acid 2-phenoxyethyl ester is also preferred.

The aminofluorane compound and the sulfonic acid ester are generally used in approximately stoichiometric amounts, one per amino group or preferably two aralkyl groups are introduced. An excess from Z. B. 10-15% of one of the components is also possible.

The reaction is advantageously carried out at elevated temperature, preferably at 80 to 120 ° C and in the presence of an acid-binding Means.

Suitable acid-binding agents are e.g. B. alkali metal hydroxides, alkaline earth metal hydroxides, Alkali metal bicarbonates, alkali metal carbonates or tertiary nitrogen bases, such as. B. pyridine, N-methylpiperidine or Trialkylamines or mixtures of these compounds. Is preferred Sodium.

The reaction preferably takes place in a non-polar, especially aromatic solvents, such as. B. benzene, toluene, xylene, chlorobenzenes such as dichlorobenzene or trichlorobenzene, or nitrobenzene instead. Preferred The solvent is toluene or xylene.

After the condensation reaction, the N-aralkylated aminofluorane compound isolated in a conventional manner, for example by adding the solvent removed by steam distillation, then the N-aralkylated Aminofluoranverbindung filtered off and dried. If necessary, the aralkylated aminofluorane compound by recrystallization, e.g. B. in Isopropanol.

In the following examples, percentages mean percentages by weight.

Example 1

12 g of 2-amino-3-methyl-6-diethylaminofluoran (according to DE-AS 20 01 864, Example 6) are in 28 g of toluene with 8.7 g of sodium carbonate stirred and heated to 100 ° C. Then a solution is left of 23.6 g of benzyl p-toluenesulfonate (prepared according to the monthly magazine chemistry 82, pp. 452-459, 1951) in toluene at 100-105 ° C in the course drop of 2 hours. The mixture is stirred for a further 8 hours at 100 ° C, carries to 100 g of water, whereupon the toluene phase is separated off and 3 times with 50 g of water is washed. After drying over sodium sulfate and Filtration, the toluene is distilled off under reduced pressure. The Crude product is taken up in a little isopropyl alcohol and as crystalline Product filtered off at 20 ° C. After drying, 12 g of one are obtained Fluoran compound of the formula

Yield: 69% of theory
Melting point: 154-155 ° C

On acid-modified silica gel, this compound immediately gives a red one Colour.

Example 2

12 g of 2-amino-3-methyl-6-diethylaminofluoran in 60 ml Toluene heated to 100 ° C with 12.4 g of potassium carbonate. Then 39.3 g p-Toluenesulfonic acid benzyl ester, dissolved in 51 g toluene, within Dosed at 100-105 ° C for 1 hour. One removed from the reaction mixture Analysis sample already shows 68.8% condensation product in the liquid chromatogram (LC) of formula (11). The reaction is continued for 1 hour Kept reflux. The analysis sample now taken gives 99.2% Reaction product.

The reaction product is clear filtered from the inorganic salt, whereupon the filtrate is concentrated and stirred with 75 ml of isopropanol. The crystallized condensation product is filtered off and weighed  Drying 10.5 g. According to LC analysis, a further 2.1 g of are in the filtrate Dibenzylaminofluoran compound according to formula (11), but none corresponding monobenzylaminofluoran compound.

Comparative example

12 g of 2-amino-3-methyl-6-diethylaminofluoran in 60 ml of toluene 12.4 g of potassium carbonate heated to 100 ° C. This is followed by a solution from 19 g of benzyl chloride in 51 g of toluene within one hour 100-105 ° C metered. An analytical sample taken from the reaction mixture shows no condensation product of formula (11) in the LC. The reaction is held at reflux for 1 hour. Another drawn Analytical sample still contains no dibenzylaminofluoran compound of formula (11), but only 3.2% of the corresponding N-monobenzylated Aminofluorane compound.

The reaction mixture is filtered clear of the inorganic salt, whereupon the filtrate is concentrated and stirred with 75 ml of isopropanol. To this By filtering off the crystallized product 8.3 g of the 2-amino-3-methyl-6-diethylaminofluorane used as the starting material recovered.

By concentrating the filtrate, the condensation proceeds slightly Ahead. LC analysis shows 1.7 g of monobenzylamino and 1.1 g of dibenzylaminofluoran compound.

Example 3

10 g of 2-amino-3-methyl-6-diethylaminofluoran in 40 ml Xylene (mixture of isomers) with 10.4 g of potassium carbonate and 21.9 g of 2-phenoxy ethyl p-toluenesulfonate (prepared according to J. Org. Chem. 9 (1944), 235, 238-240) for 11 hours at 137-140 ° C under reflux. Then are added with a further 50 ml of xylene and extracted several times with each 100 ml water at 50 ° C. The xylene phase is then concentrated to the condensation product crystallized out. The product is filtered off, washed with isopropanol and dried. 3.1 g of the compound are obtained of the formula

in the form of colorless crystals. Melting point 189-191 ° C. On acid modified Silica gel creates a toluene solution of this product instant black color.

Example 4

The filtrate obtained according to Example 3 results after column chromatography (Silica gel, eluent: toluene / ethyl acetate (20: 1)) 2.8 g of the fluoran compound of the formula

which, recrystallized from isopropanol / toluene (10: 1), has a melting point from 117-119 ° C.

On acid-modified silica gel, this compound immediately creates one Red color.

Example 5

9.6 g of 2-amino-3-diethylaminofluoran in 50 ml of xylene 6.9 g of potassium carbonate and 14.6 g of 2-phenoxyethyl p-toluenesulfonate under heated with good stirring and under reflux at 133-137 ° C for 22 hours held. The reaction mixture is with 50 ml of xylene and at 80 ° C. 100 ml of water are added. The xylene phase is then separated off, several times washed with water and concentrated. 20 g of the crude reaction mixture are obtained. Using column chromatography (silica gel, eluent: Toluene / ethyl acetate (10: 1)) are the fluoran compounds of the Formulas (14) and (15) separated and each recrystallized from isopropanol.

M.p. 124-127 ° C.

Mp 143-146 ° C.

On acid-modified clay, the compound of formula (14) develops one green color, the compound of formula (15) a black color.

Claims (7)

1. A process for the preparation of N-aralkylated aminofluorane compounds, characterized in that a fluoran compound of the formula in the
ring A is unsubstituted or substituted by halogen, nitro, amino, mono-lower alkylamino or di-lower alkylamino,
R₁ and R₃, independently of one another, are each hydrogen, halogen, lower alkyl or lower alkoxy,
R₂ is hydrogen, lower alkyl or lower alkoxy,
X₁ and Y₂, independently of one another, are each hydrogen, unsubstituted or substituted by halogen, hydroxy, cyano or lower alkoxy alkyl having at most 12 carbon atoms, cycloalkyl, aryl or acyl or (X₁ and X₂) together with the common nitrogen atom a five- or six-membered heterocyclic radical mean with an arylsulfonic acid aralkyl ester of the formula Z-SO₂-OY (2) wherein Z is an aryl radical and
Y represents an arylalkyl or aryloxyalkyl radical. 2. The method according to claim 1, characterized in that one Arylsulfonic acid aralkyl esters of the formula (2), in which Y is the arylalkyl radical means used. 3. The method according to any one of claims 1 and 2, characterized in that as arylsulfonic acid aralkyl ester a p-toluenesulfonate arylalkyl ester, a p-bromobenzenesulfonic acid aryl alkyl ester or one p-Nitrobenzenesulfonsäurearylalkylester used.   4. The method according to claim 3, characterized in that as Arylsulfonic acid aralkyl ester p-toluenesulfonic acid benzyl ester used. 5. The method according to claim 1, characterized in that as Arylsulfonic acid aralkyl ester p-toluenesulfonic acid 2-phenoxyethyl ester used. 6. The method according to any one of claims 1 to 5, characterized in that that one uses a fluoran compound of formula (1) in which R₂ is hydrogen or lower alkyl. 7. The method according to any one of claims 1 to 6, characterized in that that one uses a fluoran compound of formula (1) in which R₂ Methyl means.