DD224592A1 - PROCESS FOR THE PREPARATION OF 3-SUBSTITUTED CUMARINES - Google Patents

Abstract

The invention relates to a process for the preparation of 3-substituted coumarins, which are used as dyes, optical brighteners and organic intermediates. The coumarins are prepared in a one-pot process by reacting N, N-disubstituted 3-aminophenol-trimethylsilyl ethers with the Vilsmeier adduct of dimethylformamide and phosphorus oxychloride and further condensation of the reaction product without intermediate isolation with an active methylene component at 70 to 100C.

Description

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3-substituted coumarins of the formula I are known. They are used as optical brighteners, as dyes for synthetic fibers and for laser technology and are also interested in pharmaceuticals and pesticides. The preparation of the technically important coumarins of the formula I is carried out by acid or base-catalyzed aldol condensation of Ν, Ν-disubstituted Aminosalizylaldehyden the formula

III ι

where R ₂ and R _{3 have} the abovementioned meaning, with CH-active compounds (DE-AS 1898125).

According to this synthesis method, the Aminosalizylaldehyde of formula III are required, which are available only in moderate and unsatisfactory yields. Therefore, many manufacturing methods for these aldehydes are known, but do not yield higher than 60% of theory. This makes their application to coumarin synthesis significant

limited.

A further disadvantage is that the aldehydes obtained in a known manner are very contaminated by by-products, which cumbersome and expensive purification operations are required.

The process for the preparation of fluorescent coumarins described in DE-OS 2011500 eliminates the disadvantages associated with the use of the p-Aminosalizylaldehyde isolated in crystalline form. Thereafter, it is possible, starting from Ν, Ν-disubstituted m-aminophenols without intermediate isolation of the aldehydes, with benzimidazolyl-2-acetonitriles in the 3-position by Benzimidazoylreste substituted coumarins produce.

But even this method still has the disadvantages of an unsatisfactory yield in the implementation of 3-aminophenols

with the Vilsmeier reagent on.

The Coumarinausbeuten are therefore, based on the 3-aminophenols used, also not satisfactory.

A major disadvantage of this production process is also that the reaction requires extremely large amounts of organic solvents, the separation and recovery of which means additional work steps

are expensive.

Another possibility of preparing the coumarins of the formula I is described in DE-AS 1098125, according to which the alkyl ethers of Ν, Ν-disubstituted Aminosalizylaldehyde, which are obtained in better yields, used for condensation

become.

Nevertheless, this coumarin synthesis shows significant disadvantages that significantly affect the productivity of the manufacturer.

Thus, the acrylic acid derivatives obtainable therefrom by known condensation methods are capable of coumarin ring closure only after the alkyl ethers have been split into the reactive phenolic hydroxyl group. This ether cleavage means an additional working stage for the producer and consequently leads to a reduction of the space-time yield. Far greater is the effort resulting from the required in this procedure application of anhydrous organic solvents and the need for ether cleavage Lewis acids such. Anhydrous aluminum chloride and pyridine chlorohydrate,

results.

If this process is carried out without organic solvents, the reaction in the melt can be carried out. This means a significant corrosive load on the aggregates and is therefore not very suitable for ongoing production.

Object of the invention

The aim of the invention is a new process for the preparation of coumarins of the formula I, which no longer has the disadvantages of the known technical solutions.

Essence of the invention

In pursuit of this aim, the object was to find a new process for the preparation of coumarins of formula I, which is characterized by a simple technology and without expensive intermediate stage.

It has surprisingly been found that in the formylation under the conditions of the Vilsmeier reaction from the trialkylsilyl ethers known in the literature Ν, Ν-disubstituted 3-aminophenols of the formula

г /

in which R ₂ and R _{3 have} the abovementioned meaning, functional aldehyde derivatives are formed as intermediates which make it possible, without intermediate isolation, to prepare the 3-substituted coumarins of the formula I in high yield and in a high purity in a one-pot process.

It can not be deduced from the literature that N, N-disubstituted 3-aminophenols of the trialkylsilyl ethers give rise to reactive derivatives of Ν, Ν-disubstituted amino trialkylsilyloxybenzaldehydes under the conditions of Vilsmeier's formylation, which are useful as building blocks for coumarin synthesis. It was therefore not foreseeable that with these intermediates in

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one operation by reaction with active methylene compounds of the formula

R ₁ CH ₂ R ₄ V,

in which R _{1 has} the abovementioned meaning and R ₄ = -CN, -CO ₂ CH ₃ , -CO ₂ C ₂ H ₅ , -CONHC ₆ H ₅

means, directly the 3-substituted coumarins of formula I are available in high yield and in excellent purity.

The inventive novel preparation process for coumarins of the formula I allows under mild reaction conditions, the trialkylsilyl, preferably the trimethylsilyl, of N, N-disubstituted 3-aminophenols at 20 to 40 ⁰ C with the Vilsmeier react reagent and after the hydrolysis of the reaction mixture with the methylene component to be condensed by simple heating to 70 to 100 ° C, wherein the coumarin formed precipitates already during the reaction in the heat or water-soluble coumarins of the formula I after cooling to room temperature, optionally by salting out,

is obtained.

The advantages of the new production method according to the invention over the prior art are:

- Reduction of the energy expenditure in the Formylierungsstufe

- Low risk of danger due to low reaction temperature and low heat of reaction during the hydrolysis of the formylation mixture

- Use of simple technical units

- Significantly reduced corrosion damage to equipment

- No cleaning operations, thus high space-time yield

- high degree of conversion

- easy insulating the end products.

Thus, the inventive method is characterized over the previously known technical solutions by a

significantly higher technical and economic effectiveness.

The following exemplary embodiments are intended to explain the invention in more detail.

Exemplary embodiments Example 1

In the reaction vessel, 22 parts of dimethylformamide are introduced with stirring and cooling and 10 parts of phosphorus oxychloride are added dropwise so that the temperature does not exceed 20 ⁰ C. Subsequently, 24 parts of m-Diethylaminophenyltrimethylsilylether are added dropwise so that the temperature reaches a maximum of 20 ⁰ C. The mixture is stirred for 2 h without cooling (25 to 30 ⁰ C) and then hydrolyzed with 100 parts of ice. Of the resulting clear yellow solution 15.7 parts of 2-Cyanmethylbenzimidazol added, stirred and heated to 85 ⁰ C. The spontaneously separating dye is filtered off after cooling to room temperature and dried. This gives 23 parts of a dye of the formula

VI

with a melting point of 239 to 241 ⁰ C. Example 2

15.7 parts of 2-cyanomethylbenzimidazole and 5.2 parts of magnesium oxide are slurried with 40 parts of water and heated to 50 ⁰ C. Then added dropwise 25 parts of dimethyl sulfate so that the temperature does not exceed 70 ⁰ C. The mixture is stirred for 1 h at this temperature and then cooled to 0 to 5 ⁰ C. The thus prepared methylation solution is added to the reaction mixture prepared according to Example 1 from 22 parts of dimethylformamide, 10 parts of phosphorus oxychloride and 24 parts of m-diethylaminophenyl-trimethylsilyl ether, 10 parts of conc. Dropped hydrochloric acid and stirred for 1 h at 80 to 9O ⁰ C. After cooling to room temperature, 50 parts of saturated sodium chloride solution are added and the reaction product is filtered off with suction. After drying, 48 parts of a dyestuff of the formula

ti:

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Example 3

In a prepared according to Example 1 hydrolysis 19 parts of the compound of formula

VIII

added, stirred and heated to 90 ° C for 1 h. The dye which already partially separates on cooling to room temperature is precipitated by the addition of 20 parts of sodium chloride, filtered off with suction and dried. This gives 41 parts of a dye salt, which corresponds to about 100 parts of the known commercial product.

The dye is identical to that of Example 2.

The intermediate of the abovementioned formula is obtained when the methylation solution obtained according to Example 2

alkaline and sucks.

The crude product thus obtained can be used directly for condensation.

Example 4

In a prepared according to Example 1 hydrolysis 7 parts of malononitrile are added and 1 h at 80 to 90 ⁰ C.

touched.

The spontaneously separating dye is filtered off with suction after cooling to room temperature.

This gives 20 parts of З-Суап-7-diethyl-aminocoumarin of melting point 229 to 230 ° C.

Example 5

In a hydrolysis solution prepared according to Example 1, 11.7 parts of benzyl cyanide are added dropwise and at 80 to 90 ° C for 1 h

touched.

After cooling and suction, 25 parts of the known S-phenyl ^ -diethyl-aminocoumarin are obtained.

Example 6

21 parts Benzimidazolylessigsäureethylester are added and stirred at 80 to 90 ⁰ C for 1 h in a prepared according to Example 1 hydrolysis. The procedure is analogous to Example 1 and receives 30 parts of benzimidazolyl-7-diethyl-aminocoumarin. The dye is identical to the product prepared according to Example 1.

Example 7

In a prepared according to Example 1 hydrolysis 25.2 parts Benzoxazolylacetanilid are added and stirred at 80 to 90 ⁰ C for ² h. After cooling to room temperature, it is diluted with 50 parts of saturated sodium chloride solution and filtered with suction. After drying, 30 parts of the known S-Benzoxazolyl ^ -diethyl-aminocoumarin obtained.

Claims (1)

-1- 642 93 Invention claim: Process for the preparation of 3-substituted coumarins of the formula (D, in the R ₁ = -CN, -COrAlkyl, -CO-alkyl, -CO-aryl, -CONH ₂ , -CONH-alkyl- -CONH-aryl, -CO-N-dialkyl, CO-N-diaryl, -CO-N -alkyl, aryl, - substituted aryl or heterocyclic radicals, wherein the heterocyclic radical R, the formula (II) in which X represents a bivalent radical which complements the nitrogen-containing ring to a 5- or 6-membered ring, and A is optionally a fused aromatic ring, and their quaternary salts which may be substituted at the fused aromatic ring and R ₂ and R _{3 is} methyl or ethyl radicals, where R ₂ and R _{3 may be} identical or different and R _{2 may} also be the benzyl radical, characterized in that trimethylsilyl ether of the 3-aminophenols of the formula (IV), - "J in which R ₂ and R _{3 have} the abovementioned meaning, are reacted at 20 to 40 ° C in dimethylformamide with phosphorus oxychloride and after hydrolysis with water, the reaction mixture without intermediate isolation with the active Methylene component of the formula RiCH ₂ R ₄ (V), in which R _{1 has} the abovementioned meaning and R ₄ = -CN, -CO ₂ CH ₃ , -CO ₂ C ₂ H ₅ , -CONHC ₆ H ₅ mean, is reacted at 70 to 100 ⁰ C in a one-pot process directly to coumarin. Field of application of the invention The invention relates to a novel process for the preparation of 3-substituted coumarins of the formula in the R ₁ = -CN, -COrAlkyl, -CO-alkyl, -CO-aryl, -CONH ₂ , -CONH-alkyl, -CONH-aryl, -CO-N-dialkyl, -CO-N-diaryl, -CO- N-alkyl, aryl, substituted aryl or heterocyclic radicals,
wherein the heterocyclic radical R _{1 of} the formula where X represents a divalent radical which complements the nitrogen-containing ring to a 5- or 6-membered ring and optionally represents a fused ring, and their quaternary salts attached to the fused aromatic ring can be substituted as desired. R ₂ and R ₃ are methyl or ethyl radicals, wherein R ₂ and R _{3 may be the} same or different and R _{2 is} also the benzyl radical represents. The coumarins are partly known dyes, optical brighteners and organic intermediates.