CS251252B1 - Process for the preparation of 2,5-dialkoxy-4-morpholino-anilines and their sulphates - Google Patents

Abstract

A method for the production of 2,5-dialkoxy-4-morpholino-anilines and their sulfates of the formula where R is an alkyl with 1 to 5 carbons and n is 0 or 0.5 to 2 by treating 2,5-dialkoxy-4-morpholino-nitrobenzenes in an aqueous or organic solvent environment and with the addition of a catalyst with hydrogen at a temperature of 40 to 140 °C and a pressure of 0.1 to 5 MPa, the catalyst is first separated from the obtained reaction product and then 2,5-dialkoxy-4-morpholino-aniline is isolated. Valuable semi-finished products for the production of light-sensitive diazonium compounds for diazography.

Description

The invention solves a process for the production of the formula

2,5-dialkoxy-4-morpholino-anilines and their sulphates

wherein R is alkyl of 1 to 5 carbons and n is or 0.5 to 2.

2,5-dialkoxy-4-morpholino-anilines and their sulfate salts, particularly useful for the production of photosensitive diazonium compounds, are valuable semi-finished products used in diazography.

The preparation of these compounds has not been described separately in the literature. It is only known, for example from US Pat. 3,028,240, Br. U.S. Pat. No. 853,020 that 2,5-dialkoxy-4-morpholino-anilines can be prepared from 2,5-dialkoxy-4-morpholino-nitrobenzenes by reduction with zinc dust in hydrochloric acid with the addition of alcohol or also catalytic hydrogenael without specifying the specific processing conditions and yield . A method for preparing the sulfate salts of these substituted anilines is not published in the literature at all.

Dialkoxymorpholinoanilines are volatile compounds readily subject to decomposition by light, oxygen and elevated temperature. These properties are of great importance for the selection of a suitable process for their production, for example, it is desirable that the reduction be carried out in a short time with the exclusion of air atmosphere, the method of isolation of the product from the reaction mixture being as simple as possible and high purity of the product. Zinc dust reduction procedure in sulfuric acid solution, resp. yet with the addition of ethanol, it is technically unsuitable because, because of the minimal consumption of zinc, the reduction needs to be carried out over a long period with gradual zinc dosing. Further problems of this process are in the isolation of 2,5-dialkoxy-4-morpholinoanilines or their sulfate salts from the reaction mixture after reduction and in a considerable amount of waste products. Reduction of 2,5-dialkoxy-4-morpholino-nitrobenzenes alone by catalytic hydrogenael in the absence of another inert medium does not proceed well with the result that the catalyst is deactivated by polymer formation and the conversion of the substituted nitrobenzene starting material is not complete.

We have now found a process for the preparation of 2,5-dialkoxy-4-morpholinoanilines and their sulfates of the general formula

wherein R is an alkyl of 1 to 5 carbons and n is 0 or 0.5 to 2, characterized in that the 2,5-dialkoxy-4-morpholino-nitrobenzenes of formula II

wherein R is as defined above, is treated in a water or organic solvent medium with hydrogen addition at a temperature of 40 to 140 ° C and a pressure of 1 to 5 MPa, whereupon the catalyst is first separated from the reaction product obtained and then optionally isolated

2,5-dialkoxy-4-morpholino-aniline, or optionally to a solution of 2,5-dialkoxy-4-morpholino-aniline obtained after catalyst separation or a solution of isolated 2,5-dialkoxy-4-morpholino-aniline in an organic solvent, which are aliphatic saturated alcohols or aliphatic ketones having 1 to 6 carbons, either alone or in admixture with water, react with sulfuric acid or an aqueous solution thereof in an amount of 0.5 to 2 mol of acid per 1 mol of 2,5-dialkoxy-4-morpholine -aniline at a temperature of up to 50 ° C and the precipitated sulfate salt is isolated as a solid, for example by filtration at 30 to -20 ° C.

The catalysts used in the process according to the invention are metals of group VIIIb of the Periodic Table of the Elements in finely powdered form either alone or on supports, optionally containing up to 10% aluminum. The catalyst is separated by filtration or sedimentation, whereby the catalyst is separated as a solid product at a temperature where 2,5-dialkoxy-4-morpholinoaniline is in the liquid state or in solution. Isolation of 2,5-dialkoxy-4-morpholino-anilines is accomplished by conventional isolation methods for separating solids from liquids, e.g., by filtration or sedimentation at temperatures from -30 to 50 ° C, wherein 2,5-dialkoxy-4-morpholino-aniline they form a solid phase or are precipitated in the solid phase by cooling from an organic solvent solution.

According to the process of the invention, 2,5-dialkoxy-4-morpholinoanilines are preferably prepared by reduction of the nitro group by catalytic hydrogenation from the corresponding substituted nitrobenzene in an inert liquid medium such as ethanol, aqueous ethanol, most preferably water or acetone in an amount of 0, 1 to 10 parts by weight per 1 part of 2,5-dialkoxy-4-morpholino-nitrobenzene. A hydrogenation catalyst such as palladium on activated carbon, Raney nickel, nickel on alumina in an amount of 0.01 to 10% by weight to the starting 2,5-dialkoxy-4-morpholino-nitrobenzene is used and the reduction is carried out at a temperature of 50 to 140 ° C, preferably 60 to 100 ° C, under a hydrogen pressure of 0.2 to 10 MPa. The hydrogenation time is 1 to 18 hours depending on the hydrogenation conditions and up to 100% conversion of the starting 2,5-dialkoxy-4-morpholino-nitrobenzene is achieved. After the hydrogenation has been carried out, the catalyst is easily removed, for example by filtration at a temperature above the melting point

2,5-dialkoxy-4-morpholino-aniline if the inert medium is water, or by filtration at lower temperatures when the organic solvent is used in the hydrogenation, but the filtration temperature must be above the saturated solution temperature of the corresponding dialkoxymerfollnoaniline.

Isolation of substituted anilines from the hydrogenation products after removal of the catalyst is easy, especially when the hydrogenation is carried out in an aqueous medium. It is sufficient to cool the reaction product after filtration to a temperature below the melting point of the respective substituted aniline and then to separate the precipitated solid substituted aniline from the aqueous phase by conventional means since it is insoluble in water and has a higher density than water.

When using organic solvents, cooling to low temperatures is necessary to eliminate the substituted aniline in solid form in high yield. It is then isolated, for example, by filtration followed by drying, or it is possible to further process the undried product, for example in the preparation of diazonium salts. Another possibility is to precipitate directly from the solution of the substituted aniline sulfuric acid into the sulphate salt, whose solubility in organic solvents is considerably lower and allows an efficient method of isolation.

It has been found that 2,5-dialkoxy-4-morpholine sulphate salt can be advantageously prepared and isolated so that 1 part by weight of the compound is used. 2,5-dialkoxy-4-morpholino-aniline is dissolved in 1 to 20 parts by weight of an organic solvent, e.g. ethanol or other aliphatic alcohols, aliphatic ketones, preferably in acetone, and acid is added to the obtained solution with stirring and cooling sulfuric acid in an amount of 0.5 to 2 mol per 1 mol of substituted aniline at temperatures up to 40 ° C, whereby the sulphate salt precipitates in solid form and, after cooling, is isolated e.g. by filtration, washed with solvent and further processed as such or further dried preferably under vacuum and in the dark. Filtration and washing can be carried out, for example, at a temperature of 20 to 30 ° C, if used e.g. acetone as an organic solvent, in the case of other solvents such as ethanol, it is necessary to cool the suspension to lower temperatures prior to filtration in order to reduce solubility losses and increase yield.

AND

It has been found that when the amount of sulfuric acid in the stoichiometric ratio corresponding to normal sulphate or acid sulphate is used to prepare the substituted aniline sulphate salts, salts of a uniform composition are not formed but a sulphate-acid sulphate mixture with a higher sulfuric acid content and free amine base. The amount of free amine base is suppressed with an increased amount of sulfuric acid, but a large excess is not suitable, since the sulfate salts are deposited in the paste form and condensation cakes also occur to form colored substances. The advantage of the preparation of sulphate salts in organic solvents is that the residual amount of the free amine base remains dissolved in the organic solvent during sulphate recovery, but the refining effect is particularly important, since other undesirable impurities, especially coloring substances, are photochemical by-products. decomposition. Thus, by the process of preparing the sulfate salts of the present invention, it is possible to obtain the sulfate salts of substituted anilines as white color products of high purity, which are more stable to decomposition than the pure free base and are also more suitable for the preparation of diazonium salts.

The production process of the 2,5-dialkoxy-4-morpholino-anilines of the invention achieves up to 99% yields and good product quality without refining operations. The process is simple, technically easy to carry out and economically advantageous. The mild temperature conditions of the process and, moreover, the hydrogen atmosphere, minimize decomposition and by-product formation, achieving up to 100% conversion of the substituted nitrobenzene feedstock. The amount of waste material is minimal and easy to dispose of. The catalyst can be used for several manufacturing operations or, in other operations, the catalyst used from the previous operation can be added with a small proportion of fresh catalyst, thus achieving further economic advantage.

The process for producing the sulfate salts of the 2,5-dialkoxy-4-morpholinoanilines of the present invention is very simple in technical terms and achieves up to 95% yields in obtaining high quality sulfate salts and free of color compounds, which is a prerequisite for further their processing, for example, into diazonium compounds for diazographic materials.

Further details follow from the examples. In the examples, parts are parts by weight, percentages are percentages by weight, percentages are expressed as percentages of the theory of 2,5-dialkoxy-4-morpholino-aniline obtained based on the starting amount

2,5-dialkoxy-4-morpholino-nitrobenzene, in the case of sulphate salts, as a percentage of the theory, to the content of the 2,5-dialkoxy-4-morpholino-aniline component in the sulphate salt obtained relative to the starting amount of 2,5-dialkoxy-4-morpholino -aniline _f unless otherwise indicated. The melting points of the products are determined by Kofler.

Example 1

A mixture of 60 parts of 2,5-dibutoxy-4-morpholino-nitrobenzene, 200 parts of water and 1.2 parts of Raney-Nickel catalyst was reduced in an autoclave at 80 ° C and 2.5 MPa for 12.5 h. Upon completion of the reduction, the hydrogenation product was cooled to 65 ° C, filtered and the catalyst separated in solid form. The filtrate was cooled to 25 ° C and after separation of the aqueous layer, 54.8 parts of 2,5-dibutoxy-4-morpholino-aniline were obtained as a crystalline white-gray melt, m.p. 54-59 ° C. 99.8% yield.

Example 2

In contrast to the procedure of Example 1, hydrogen reduction was carried out at 100 ° C for 3.5 hours. 52.6 parts of 2,5-dibutoxy-4-morpholino-aniline of the same appearance were obtained, m.p. ° C, i.e. in a yield of 95.8%.

Example 3

54.8 parts of 2,5-dibutoxy-4-morpholino-aniline prepared according to Example 1 are dissolved in 124 parts of acetone at 25 ° C, and then, while maintaining the temperature at 18-20 ° C by cooling, gradually admixing with stirring. 5 parts of 98% sulfuric acid. The precipitated crystalline product is isolated by filtration, the filter cake is washed with acetone to a colorless liquor and then dried in the dark under reduced pressure of 5 kPa. 55.25 parts of 2,5-dibutoxy-4-morpholino-aniline sulfate salt are obtained in the form of a white-gray solid with an analysis of 83.1% of 2,5-dibutoxy-4-morpholino-aniline and 16.8% of acid. sulfur, i.e. in a yield of 83.7%.

Example 4

In contrast to the procedure of Example 3, 0.35 parts of 98% sulfuric acid was added per part of 2,5-dibutoxy-4-morpholino-nitrobenzene. The product was obtained by analysis containing 58% 2,5-dibutoxy-4-morpholinoaniline and 25.5% sulfuric acid, according to chromatographic analysis except acetone without other impurities, white color with a blue tint in a yield of 94.4%.

Example 5

A mixture of 90 parts of 2,5-dibutoxy-4-morpholino-nitrobenzene, 143 parts of acetone and 1.8 parts of catalyst containing 3% palladium metal on activated carbon as the carrier is reduced in an autoclave with hydrogen at 60 ° C and a pressure of 2 to 2 After a reduction, the reaction mixture was cooled to 25 ° C, the catalyst was removed by filtration as a solid, and 87 parts of acetone were added to the filtrate with stirring and cooling, followed by 29.9 parts of 98% sulfuric acid. so that the temperature does not exceed 35 ° C. After cooling to 20 ° C, the resulting suspension was filtered and the filter cake washed with acetone. 109.8 parts of a filter cake, a white paste are obtained, after drying in the dark and under a vacuum of 1 kPa, 86.93 parts of a white-gray sulphate product according to analysis containing 76.3% 2,5-dibutoxy-4-morpholino-aniline and 22%. Sulfuric acid, according to chromatographic analysis, except acetone without other impurities, ie in a yield of 81.6% of the theoretical content of the 2,5-dibutoxy-4-morpholino-aniline component in the obtained sulfate salt and based on the starting amount of 2,5-dibutoxy -4-morpholino-nitrobentene.

Example 6

A mixture of 84.1 parts of 2,5-diethoxy-4-morpholino-nitrobenzene, 170 parts of water and 10 parts of Raney-Nickel catalyst in an autoclave was reduced with hydrogen at 100 ° C and 2.5 MPa for 18 h. to 25 ° C and after separation of the aqueous phase by filtration, 85.6 parts of a solid product are obtained in the form of a melt consisting of a white crystalline mass of 2,5-diethoxy-4-morpholino-aniline, m.p. 93-95 ° and a black deposited catalyst mass. . According to chromatographic analysis, in addition to the catalyst and unreacted nitro compounds up to 1% no other impurities were found. Product yield after deduction of catalyst mass 99%.

Example 7

43.3 parts of the obtained solid product were dissolved in 120 parts of acetone according to the preparation of Example 6 and the catalyst was collected as a solid by filtration. 14.06 parts of 98% sulfuric acid are added to the filtrate with stirring and cooling over 10 minutes. After cooling to 6 ° C, the resulting suspension is filtered, the filter cake is washed with acetone until the color disappears. After drying the filter cake, 49.02 parts of the sulphate salt are obtained as a white product, according to analysis containing 68.6% of the 2,5-diethoxy-4-morpholino-aniline component, i.e. in a yield of 88.0%. According to chromatographic analysis, besides acetone and sulfuric acid, no other impurities are present.

AND

251252,

Example 8

A mixture of 75.29 parts of 2,5-diethoxy-4-morpholino-nitrobenzene, 160 parts of acetone and 3 parts of a catalyst containing 3% palladium on activated carbon is reduced in an autoclave with hydrogen at 80 ° C and 2.5 MPa. After cooling to 25 ° C, the catalyst is removed by filtration as a solid. Under stirring and cooling, 24.9 parts of 98% sulfuric acid are added to the filtrate and the precipitate formed is filtered off at 10 ° C, the filter cake is washed with acetone and dried to give 68.2 parts of 2,5-diethoxy-4 sulfate salt. morpholino-aniline in the form of a white-gray powder containing 68.0% of 2,5-diethoxy-4-morpholino-aniline component. The yield was 68.2% of theory based on the aniline component content of the salt obtained and based on the starting 2,5-diethoxy-4-morpholino-nitrobenzene. According to chromatographic analysis, in addition to the main components and residual acetone, no impurities were found.

Other 2,5-dialkoxy-4-morpholino-anilines and their sulfate salts can be prepared by analogous procedures to those described in the Examples, in which the alkoxy group is methoxy, propoxy, isopropoxy or isoamyloxy.

Claims (4)

1. A process for the preparation of 2 _< 5 > -dialkoxy-4-morpholinoanilines and their sulphates of the general formula I wherein R is an alkyl of 1 to 5 carbons and n is 0 or 0.5 to 2, characterized in that The 4-morpholino-nitrobenzenes of the formula II wherein R is as defined above, are treated in a medium of water or an organic solvent and added to the catalyst with hydrogen at a temperature of 40 to 140 ° C and a pressure of 1 to 5 MPa. of the reaction product first separates the catalyst and then optionally isolates 2,5-dialkoxy-4-morpholino-aniline, or optionally to a solution of 2,5-dialkoxy-4-morpholino-aniline obtained after separation of the catalyst or to a isolated 2,5- dialkoxy-4-morpholino-aniline in an organic solvent, which are aliphatic saturated alcohols or aliphatic ketones with 1 to 6 carbons, either alone or in admixture with water, treat sulfuric acid or its aqueous solution in an amount of 0,5 to 2 mol of acid 1 mol of 2,5-dialkoxy-4-oxo-olefin The compound is isolated as a solid, e.g., by filtration at 30 to -20 ° C. 2,5-dialkoxy-4-morpholino-aniline in liquid or in solution form. 2. A process according to claim 1, wherein the catalyst is a Group VII metal of the Periodic Table of the Elements in finely powdered form either alone or on supports, optionally containing up to 10% aluminum. 3. The process of claim 1 wherein the catalyst is separated by filtration or sedimentation, wherein the catalyst is separated as a solid product at a temperature where 4. A process according to claim 1, wherein the isolation of 2,5-dialkoxy-4-morpholino-anilines is carried out by conventional isolation methods for separating solids from liquids, e.g. by filtration or sedimentation, at temperatures of from 30 to 50 [deg.] C. 2,5-dialkoxy-4-morpholino-aniline forms a solid phase or precipitates in the solid phase from the organic solvent solution.