RU2378273C1 - Method of producing 3,4-dithienyl-substituted maleic anhydrides or maleimides - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing new 3,4-dithienyl-substituted maleic anhydrides or maleimides of general formula I:

, where X=O, or NR₁; R₁ and R₂=alkyl C₁-C₄; R₃=alkyl C₁-C₄, or nitrogen- and/or sulphur-containing heterocyclic substitute. The method involves reacting the corresponding 2,5-disubstituted 3-thienyl-acetic acid with the corresponding 2,5-disubstituted 3-halogen acetythiophenes while heating in the presence of a base in a medium of inert organic solvent in atmospheric oxygen with subsequent separation of the end product of general formula I, where X=O, or, if necessary, the latter is converted to a compound of general formula I, where X=NR₁, where R₁ assumes values given above, by treating it with the corresponding amine. These compounds can be used as photochromes, which are widely used as optical switches in high-capacity data carriers used for recording, processing and storing data.

EFFECT: versatility of the method, ie possibility of obtaining compounds with and without equivalent heterocyclic substitutes using readily available thienyl-acetic acid and halogen ketones of the thiophene family, which considerably widens the assortment of organic photochromic dithienylethenes.

4 cl, 5 ex

Description

The invention relates to the field of producing organic photochromes, in particular new photochromic dithienylethenes not described in the literature, containing a fragment of maleic anhydride or maleimide as a bridge link. Photochromic products of this class are widely used as optical switches in high-capacity storage media used for recording, processing and storage of data. Photochromic compounds that can be used as such should have a certain set of operational characteristics: thermal irreversibility of both forms, high quantum yield of photoconversion, and also high cyclicity. One of the classes of photochromes satisfying these conditions is 1,2-thienylethenes, in particular, products containing a maleic anhydride or maleimide fragment as an ethene bridge.

The literature describes several methods for producing photochromic dithienylethenes containing a maleic anhydride fragment as a bridge link. Thus, there is a known method for producing the desired 3,4-dithienyl substituted maleic anhydrides, which involves the treatment of cyclobut-3-ene-1,2-dione derivatives with 90% hydrogen peroxide in acetonitrile at 30-40 ° C. (Photochromic digitariethenes. 8. A new approach to the synthesis of 3,4-bis (2,5-dimethyl-3-thienyl) furan-2,5-dione as potential photochrome. Shirinyan VZ, Krajushkin MM, Belenky L.I., Vorontsova L.G., Starikova Z.A., Martynkin A.Yu., Ivanov V.L., Uzhinov B.M., HGS, 37 (1), 2001, 81-88). However, this method does not allow to obtain the target compounds with nonequivalent thiophene fragments. In addition, this method is applicable for a very narrow range of starting compounds. A significant disadvantage of this method is the use of explosive concentrated hydrogen peroxide.

There is also known a method for producing 3,4-dithienyl substituted maleic anhydrides based on the processing of 3,4-dithienyl substituted derivatives of maleic dinitrile with alkali in ethylene glycol monoethyl ether with prolonged boiling. (Thermally irreversible photochromic systems. Reversible photocyclization of diarylethene derivatives. Irie M., Mohri M., J. Org. Chem., 53 (4), 1988, 803-808). It should be noted that this method is also not universal, since it is not applicable for the synthesis of photochromic products with nonequivalent heterocyclic substituents. In addition, the target maleic anhydride is formed in this case with a rather low yield (20%).

The literature describes several methods for producing photochromic 3,4-dithienyl substituted maleimide derivatives based on the corresponding maleic anhydrides. So, there is a known method for producing maleimides, which consists in the treatment of maleic anhydride with methylamine methanol at room temperature (Photochromic digitariethenes: XVII. A new synthesis of photochromic N-alkyldithienyl maleimides. Krajushkin MM, Shirinyan VZ, Belenky LI, Shimkin A.A., Martynkin A.Yu., Uzhinov B.M., ZhORkh, 38 (9), 2002, 1390-1393). However, this method is not applicable for the synthesis of photochromic 3,4-dithienyl substituted maleimide derivatives with nonequivalent heterocyclic substituents due to the absence of the corresponding starting anhydrides.

The objective of the present invention is to develop a universal method for producing organic photochromes, in particular dithienylethenes, containing as a bridge a fragment of maleic anhydride or maleimide, which allows to expand the range of organic photochromes to obtain compounds with both equivalent and nonequivalent heterocyclic substituents.

The problem is achieved by the proposed method for producing 3,4-dithienyl substituted maleic anhydrides or maleimides of the general formula I:

where X = O or NR1

R1 and R2 = alkyl C ₁ -C ₄

R3 = alkylC ₁ -C ₄ , or a nitrogen and / or sulfur-containing heterocyclic substituent, consisting in the fact that the corresponding 2,5-disubstituted 3-thienylacetic acid is reacted with the corresponding 2,5-disubstituted 3-haloacetylthiophenes when heated in the presence of a base in an inert organic solvent in an atmosphere of oxygen. The target product of general formula I, where X = O, is isolated in a known manner, or, if necessary, the latter is converted to a compound of general formula I, where X = NR1, where R1 has the above meanings, by treating it with the corresponding amine.

The process proceeds as follows:

As the basis for the above condensation, alkali metal carbonates can be used, preferably using potassium carbonate. Potassium carbonate is taken in a 3-5-fold excess in relation to the starting reagents. In the proposed production method, for the first time for a similar type of reaction, the base is used both as a condensing agent and as a cyclizing agent and an oxidation catalyst. The process is carried out in an inert organic solvent, for example, in dimethylformamide.

The process must be carried out when heated, for example, in the temperature range from 70 to 90 ° C. At lower temperature conditions of the process (<70 ° C), the reaction proceeds slowly, and an increase in temperature above 90 ° C leads to a decrease in the yield of the target product as a result of the grinding of the reaction mixture.

A key feature of the proposed method is the process in the atmosphere of oxygen, which is an oxidizing agent for the conversion of intermediate formed compounds.

The proposed method allows to synthesize maleimide derivatives of the general formula I (X = NR1) by recycling the corresponding derivatives of maleic anhydride of the formula I (X = O) under the action of an aliphatic amine. The use of an amine in a 3-5 fold excess with respect to maleic anhydride is preferred.

The process is carried out according to known methods in an inert organic solvent, for example, in ethanol when heated, preferably in the temperature range from 70 to 90 ° C in an atmosphere of oxygen. Lower temperature conditions of the process (<70 ° C) reduce the rate of the reaction, and an increase in temperature above 90 ° C leads to a decrease in the yield of the target product as a result of grinding the reaction mixture.

The method is illustrated by the following examples.

Example 1

Obtaining 3,4-bis- [2-methyl-5- (2-methylthiazol-4-yl) thiophen-3-yl] furan-2,5-dione of the formula:

A mixture of 0.16 g (0.622 mmol) of [2-methyl-5- (2-methylthiazol-4-yl) -3-thiophen-3-yl] -acetic acid, 0.17 g (0.622 mmol) of 1- [2-methyl-5 - (2-methylthiazol-4-yl) -3-thiophen-3-yl] -2-chloroethanone and 0.28 g (2 mmol) of anhydrous potassium carbonate in 4 ml of dimethylformamide are stirred at a temperature of from 70 to 90 ° C under atmospheric oxygen , in the dark, for 16 hours. Then the reaction mass is poured into water and extracted with ethyl acetate (2 * 30 ml), the organic layer is discarded, the aqueous solution is acidified with 10% hydrochloric acid to pH 2-3, 30 ml of ethyl acetate are added and stirred for 3 hours at room temperature. Then the organic layer was separated, the aqueous layer was extracted with ethyl acetate (2 * 30 ml), dried over Na ₂ SO ₄ . The solvent was evaporated, the residue was chromatographed on silica gel, eluent: petroleum ether (60-80 ° C) - ethyl acetate 3: 1, and recrystallized from ether.

Yield 0.11 g (35%), mp. 173-175 ° C. ¹ H NMR spectrum (δ, ppm) (DMSO-d ₆ ): 1.98 (s, 6H, 2CH ₃ ), 2.68 (s, 6H, 2CH ₃ ), 7.48 (s, 2H, 2CH _Het ), 7.79 (s, 2H, 2CH _Het ).

Example 2

Preparation of 3- (2,5-dimethylthiophen-3-yl) -4- [2-methyl-5- (2-methylthiazol-4-yl) -thiophen-3-yl] furan-2,5-dione of the formula:

Obtained by the method described in example 1 from (2,5-dimethylthiophen-3-yl) -acetic acid and 1- [2-methyl-5- (2-methylthiazol-4-yl) -thiophen-3-yl] -2-chloroethanone. Yield 56%, mp. 181-183 ° C. ¹ H NMR spectrum (δ, ppm) (CDCl ₃ ): 1.98 (s, 6H, 2CH ₃ ), 2.41 (s, 3H, CH ₃ ), 2.74 (s, 3H, CH ₃ ), 6.78 (s , 1H, CH _Het ), 7.21 (s, 1H, CH _Het ), 7.42 (s, 1H, CH _Het ).

Example 3

Preparation of N- (4- {4- [4- (2,5-dimethylthiophen-3-yl) -2,5-dioxo-2,5-dihydrofuran-3-yl] -5-methylthiophen-2-yl} - thiazol-2-yl) -acetamide of the formula:

Obtained by the method described in example 1 from (2,5-dimethylthiophen-3-yl) -acetic acid and N- {4- [4- (2-chloroacetyl) -5-methylthiophen-2-yl] thiazole- 2-yl} -acetamide.

Yield 48%, mp. 257-259 ° C. ¹ H NMR spectrum (δ, ppm) (CDCl ₃ ): 1.98 (s, 6H, 2CH ₃ ), 2.23 (s, 3H, CH ₃ ), 2.42 (s, 3H, COSH ₃ ), 6.70 (s , 1H. CH _Het ), 7.01 (s, 1H, CH _Het ), 7.38 (s, 1H, CH _Het ), 9.80 (s, 1H, NH).

Example 4

Preparation of 3- (2,5-dimethylthiophen-3-yl) -4- [2-methyl-5- (2-morpholin-4-ylthiazol-4-yl) -thiophen-3-yl] -furan-2,5 dione of the formula:

Obtained by the method described in example 1 from (2,5-dimethylthiophen-3-yl) -acetic acid and 1- [2-methyl-5- (2-morpholin-4-ylthiazol-4-yl) -thiophen- 3-yl] -2-chloroethanone.

Yield 41%, mp. 231-233 ° C. ¹ H NMR spectrum (δ, ppm) (CDCl ₃ ): 1.98 (s, 6H, 2CH ₃ ), 2.41 (s, 3H, CH ₃ ), 3.50 (t, 4H, 2CH ₂ ), 3.80 (t , 4H, 2CH ₂ ), 6.68 (s, 1H, CH _Het ), 6.79 (s, 1H, CH _Het ), 7.38 (s, 1H, CH _Het ).

Example 5

Obtaining 1-methyl-3,4-bis- [2-methyl-5- (2-methylthiazol-4-yl) -thiophen-3-yl] pyrrole-2,5-dione of the formula:

0.24 g (0.5 mmol) of 3,4-bis- [2-methyl-5- (2-methylthiazol-4-yl) thiophen-3-yl] furan-2,5-dione in 5 ml of a bimolar methylamine solution in ethanol is refluxed for 16 hours. Then the reaction mass is poured into water and extracted with ethyl acetate (3 * 30 ml), the organic phase is washed with water, dried over Na ₂ SO ₄ . The solvent was evaporated, the residue was chromatographed on silica gel, eluent: petroleum ether (60-80 ° C) - ethyl acetate 3: 1, and recrystallized from ether. Yield 0.16 g (67%), mp. 188-190 ° C. ¹ H NMR spectrum (δ, ppm) (DMSO-d ₆ ): 1.85 (s, 6H, 2CH ₃ ), 2.80 (s, 6H, 2CH ₃ ), 3.87 (s, 3H, NCH ₃ ), 7.33 (s, 2H, 2CH _Het ); 7.68 (s, 2H, 2CH _Het ).

Thus, a convenient universal method has been proposed for the preparation of new photochromic dithienylethenes not described in the literature with maleic anhydride and maleimide bridged fragments with both equivalent and nonequivalent heterocyclic substituents based on the use of available thienylacetic acids and thiophene halogen ketones. A special advantage of the proposed method compared with previously known is the possibility of obtaining photochromic products with nonequivalent heterocyclic substituents. The proposed method can be used both for the synthesis of previously described photochromic dithienylethenes of this type, and to obtain new products with a different combination of heterocyclic fragments. The proposed method allows to obtain compounds with fairly good yields.

A significant advantage of the proposed method compared to previously known is the production of photochromic maleic anhydrides from available thienylacetic acids and thiophene halogen ketones, which allows us to significantly expand the range of organic photochromic dithienethenes.

Claims (4)

1. The method of obtaining 3,4-dithienyl substituted maleic anhydrides or maleimides of the general formula I:

where X = O or NR ₁ ;
R ₁ and R ₂ = alkyl C ₁ -C ₄ ;
R ₃ = C ₁ -C ₄ alkyl, or a nitrogen and / or sulfur-containing heterocyclic substituent, wherein the corresponding 2,5-disubstituted 3-thienylacetic acid is reacted with the corresponding 2,5-disubstituted 3-haloacetylthiophenes when heated in presence of a base in an inert organic solvent under an air atmosphere of oxygen with subsequent isolation of the desired product of the general formula I, wherein X = O, or, if necessary, the latter is converted into a compound of general formula I, wherein X = NR _1, where R ₁ has the aforementioned e values, by treating it with the appropriate amine. 2. The method according to claim 1, characterized in that the potassium carbonate is used as the base. 3. The method according to claim 1, characterized in that dimethylformamide is used as a solvent. 4. The method according to claim 1, characterized in that the process is carried out at a temperature of from 70 to 90 ° C.