The method of obtaining 2-(furyl-2)-1,3-oxazolidine

 

(57) Abstract:

The invention relates to the field of organic chemistry, specifically to a method for producing 2-(furyl-2)-1,3-oxazolidine formula I

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with astragalina activity. The invention solves the problem of increasing the yield of products, simplifying the process of obtaining and allocating them to the reaction mixture. The invention consists in that the 2-(furyl-2)-1,3-oxazolidine produced by the interaction of substituted aminoalcohols of formula II

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where R1, R2, R3= H or C1-C4alkyl, for example 2-amino-2-methyl-propan-1-ol with furfural at a molar ratio of 1:1 at room temperature in the presence of 10% sulfuric acid as catalyst, taken in an amount of 10 ml per mol of furfural, followed by separation of the synthesized compounds by precipitation from an aqueous suspension or emulsion.

The invention relates to the field of organic chemistry, specifically to a method for producing 2-(furyl-2)-1,3-oxazolidines with like 2-aryl-1,3-oxazolidine (Zelikman H. I., Shkrebets A. I., kulenovic, B., Chemistry of heterocycle. connect. 1971, No. 3, S. 291, Melnicka, A., Khlebnikov T. D., Fedorov, C. G., proc. Dokl. VIII Mezhdunarodnie interaction diaminoalkanes with furfural, proceeding in the presence of potash at a temperature of 40oC for 3-3,5 hours and leading to the formation of 2-(furyl-2)-3-alkyl-5-aminomethyl-1,3-oxazolidines with outputs 54-57% (Kirsanov B. H., Karimov M. B. Balk. chem. zhurn., 1996, T. 3, vol. 5-6, S. 28).

Chiral 2-(furyl-2)-1,3-oxazolidine obtained by reacting (1R, 2S)-ephedrine or (1S, 2S)-pseudoephedrine with furfural in the presence of molecular sieves (F. Polyak, T. Dorofeeva, G. Zelchan, Synth Commun, 1955, 25, N 19, p. 2895).

The closest solution of the problem, that is the prototype, is a method of obtaining 2-(furyl-2)-1,3-oxazolidines by reacting furfural with substituted aminoalcohols in the environment of benzene (Senkug M., J. Amer. Chem. Soc. 1945, v. 67, No. 9, p. 1515).

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R = N(C2H5)2; N(CH2)5; N(CH2)4O

Consider it on the example of 2-(furyl-2)-4,4-dimethyl-1,3-oxazolidine.

According to the prototype of a mixture of 1 mol (89 g), 2-aminomethyl-propan-1-ol, 1 mol (96 g) of fresh furfural and 150 g of benzene is boiled in a flask equipped with a mechanical stirrer and a trap Dean-stark under reflux until the evolution stops the reaction of water (within 2-2 .5 hours). After evaporation of the solvent allocate by vacuum distillation to 92.4 g of 2-(furyl-2)-4,4-dimethyl-1,3-aktov - 60%.

2. The complexity of the hardware design (the flask with a stirrer and a trap Dean-stark).

3. The use of toxic solvent is benzene.

4. The necessity of heating up to 80oC.

5. A long reaction time is 2-2,5 hours

The aim of the invention is to increase the output and simplify the process of obtaining 2-(furyl-2)-1,3-oxazolidine.

This goal is achieved by the fact that 2-(furyl-2)-1,3-oxazolidine get interaction aminoalcohols with furfural at room temperature in the presence of an aqueous solution of sulfuric acid as catalyst

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R1, R2, R3=H or C1-C4alkyl. Selection of products from the reaction mixture is carried out by precipitation from a water suspension or emulsion. With the purity of the crystalline product after drying in air up to 99% without additional purification. For separation of liquid products is used, an additional vacuum partition.

The resulting 2-(furyl-2)-1,3-oxazolidine identified by physico-chemical constants and PMR spectra.

The method is as follows: to the mixture of amerosport with furfural, taken in equimolar amounts, PR is Le 5 - 10 minutes of intense mixing is heated and becomes cloudy. At the time of turbidity to the reaction mixture add distilled water. When this liquid products form the lower oily organic layer, the crystal comes in the form of fine sediment.

Crystalline product does not require recrystallization or vacuum distillation, because after washing and drying it is an almost pure substance (99,8%). The remaining 2-(furyl-2)-1,3-oxazolidine allocated partition under vacuum, the lower organic layer of the reaction mixture.

Compared with the prototype of the proposed method differs in that the known reaction of interaction of substituted aminoalcohols with furfural, leading to the formation of 2-(furyl-2)-1,3-oxazolidine, is carried out in different conditions: without the use of a solvent, at room temperature instead of the boiling point of benzene (80oC) in the presence of dilute sulfuric acid as a catalyst. The reaction time is reduced to 5-10 minutes.

The claimed method of obtaining 2-(furyl-2)-1,3-oxazolidine is illustrated by examples 1-11.

Example 1. Synthesis of 2(furyl-2)-4,4-dimethyl-1,3-oxazolidine (I): Henichesk the azeotropic distillation of water (volume ratio of water: furfural = 2:1, boiling point 98oC). The mixture is cooled in a water bath to room temperature and with stirring, add in one 10 ml of 10% aqueous solution of sulfuric acid. Stirring is continued for another 5-10 minutes, the exothermic reaction of acetalization the reaction mixture is heated to 40-50oC. Subsequent cooling of the reaction mixture indicates the end of the reaction and can be accelerated by immersion of the reaction beaker in a cold water bath. At the time of the turbidity of the reaction mixture, indicating the beginning of crystallization of the product to the contents of the glass in one go with constant stirring poured 200-500 ml of distilled water. Immediately begins a sharp precipitation, the degree of dispersion which depends on the intensity of mixing. After 1 minute, the reaction is completed. The reaction mixture is neutralized 10% sodium carbonate solution to pH 7, after which the product is filtered under vacuum, washed several times on the filter with distilled water and dried in air at room temperature. If necessary to obtain a homogeneous powder product can be cleaned manually through a sieve. Output (2-furyl-2)-4,4-dimethyl-1,3-Oksana, and not in a flask equipped with a mechanical stirrer and a trap Dean-stark under reflux. For mixing, you can use the magnetic stirrer, and if no mixer or just plug that does not affect the quality of the product. Conducting the reaction at room temperature simplifies installation and reduces the energy consumption for the synthesis of the product. In addition, the use of the proposed method avoids the use of toxic solvent is benzene.

Example 2. Glass load 1 mol (96 g, 83,5 ml) of furfural and 1.1 mol (97.9 g) 2-aminomethyl-propan-1-ol. The reaction is carried out analogously to example 1. The product yield 144,8 g (94%).

Example 3. In chemical glass download 1 mol (89 g), 2-aminomethyl-propyl-1-ol and 1.1 mol (105,6 g, 92 ml) of furfural. The reaction is carried out analogously to example 1. The product yield 127,8 g (83%).

As can be seen from examples 2 and 3, the optimal molar ratio of reactants is 1: 1. When used in the reaction, even a small excess of furfural yield is reduced due to losses during repeated washings with hot water required to remove unreacted furfural. A slight excess of 2-amino-methyl-propan-1-ol has virtually no effect on the output produ loading of reagents. At a temperature of 40oC poured 10 ml of sulfuric acid. The reaction mixture is partially osmoses and dark, yield 57 g (37%). The product has a brown tinge, fatal when washing.

As can be seen from example 4, the addition of a catalyst at a temperature above room temperature leads to the resinification of the reaction mixture and the reduction of product yield.

Example 5. Analogously to example 1 are loaded reagents. At room temperature, poured 3 ml of 30% aqueous solution of sulfuric acid. The reaction mixture osmoses, yield 54 g (35%).

Example 6. Analogously to example 1 are loaded reagents. At a temperature of 20oC to the reaction mixture is poured 10 cm310%-aqueous solution of hydrochloric acid. Crystallization begins only after 35 minutes. The yield of 58.5 g (38%).

Example 7. Analogously to example 1 are loaded reagents. At a temperature of 20oC to the reaction mixture add 1 cm3epirate boron TRIFLUORIDE. Add water stops beginning of the crystallization, the product remains in solution. Without the addition of water the product crystallizes in the form of a solid piece of brown color. The output of 63.1 g (41%).

Example 8. Similarly, prioi acid. Water and sodium carbonate solution to neutralize poured before crystallization. Increases the time of crystallization to 50 minutes, the yield of 46.2 g (30%).

Example 9. Analogously to example 1 are loaded reagents. Water and sodium carbonate solution is poured after crystallization. The product solidifies in the form of a monolithic piece. The product yield with 95.5 g (62%).

As can be seen from examples 8 and 9, the optimal time of prilipanie water and a neutralizing solution is the moment of crystallization.

The given examples show that the optimal ratio of 2-amino-2-methyl-propan-1-ol : furfural is 1:1, the optimum amount of catalyst 10 cm310%-aqueous solution of sulfuric acid, the optimum temperature 20oC, the optimal time of adding water and a neutralizing solution is the moment of crystallization.

In these conditions, carried out the reaction of interaction of a number of other substituted aminoalcohols with furfural.

Example 10. Synthesis of 3-butyl-2-(furyl-2)-1,3-oxazolidine (II): in chemical beaker 750 ml download 1 mol (117 g; 77,2 ml) of N-butylaminoethyl and 1 mol of furfural (96 g, 83.5 cm3), purified by azeotropic distillation with water. The reagents are mixed in the 40 to 50oC. Interaction lasts 5-10 minutes. Subsequent cooling of the reaction mixture and isolation of the reaction water (17,4 ml) in the form of lower layer indicates the end of the reaction. The organic layer was separated using a separating funnel. The aqueous layer was extracted with pentane or ether for maximum product recovery. The extract combined with the organic layer, the solvent is distilled off and the vacuum distillation give 2-(furyl-2)-3-butyl-1,3-oxazolidin with access 174,7 g (96%) (so Kip. 97oC, 3 mm RT.cent.), n2D0= 1,4642, d240= 1,0101.

Example 11. Analogously to example 10 by the interaction of 1 mol (103 g, 112,5 ml) of N-propylaminoethyl with 1 mol (96 g of 83.4 ml) of furfural get 2-(furyl-2)-3-propyl-1,3-oxazolidin with so Kip. 120oC (5 mm RT.cent.), d240= 1,0135, n2D0= 1,4634. Output 151,2 g (90%)

Example 12. Analogously to example 10 by the interaction of 1 mol (103 g, 72.4 ml) of N-isopropylaminoethyl with 1 mol (96 g of 83.4 ml) of furfural get 2-(furyl-2)-3-isopropyl-1,3-oxazolidin with so Kip. 102oC (4 mm RT. century ), d240= 1,0130, n2D0= 1,4632. Output 156,2 g (93%).

Example 13. Analogously to example 10 by the interaction of 1 mol (117 g, to 132.6 ml) of N-sibutraminebecause 1 M40= 1,0128, n2D0= 1,4635. Output 167,4 g (92%).

According to the results of primary screening astragalina, fungicidal and bactericidal activity of the synthesized compounds in NEISSER (, Moscow), synthesized 2-(furyl-2)-1,3-oxazolidine have astragalina activity level growth regulator "Krasnodar-1 and inhibit the development of pathogenic bacteria and viruses, Fusarium oxysporum, Rhizootonio solani, Alternazia solani, Venturia inacqualis, Xantomonos malvacearum, which cause such widespread plant diseases as late blight, Rhizoctonia, scab, and other currently conducted in-depth research.

Using the proposed method to obtain 2-(furyl-2)-1,3-oxazolidine allows you to:

to increase the yield of 2-(furyl-2)-1,3-oxazolidine up to 90-98%;

to reduce the reaction time to 3-3,5 hours 5-10 min;

avoid the use of toxic reaction solvent is benzene, replace it with stages of crystallization and washing with distilled water;

to reduce the reaction temperature to 80oC prototype (the boiling point of benzene) to room, which greatly simplifies the installation and reduces the power consumption when receiving data connections;

snakily product, the contaminated resin and traces of solvent.

The method of obtaining 2-(furyl-2)-1,3-oxazolidine General formula I

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where R1, R2, R3is a hydrogen atom or a C1- C4alkyl, interaction substituted amerosport formula II

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where R1, R2, R3have the above meanings, with furfural in the presence of an acid catalyst, wherein the process is carried out at a molar ratio of 1 : 1, respectively at room temperature in the presence of 10% sulfuric acid, taken in an amount of 10 ml per mol of furfural, followed by cooling the reaction mixture and adding thereto water at the time of crystallization for separation of the target product deposition from aqueous suspensions or emulsions.

 

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