RU2086550C1 - Method for production of 2-(furyl-2)-1,3-dioxanes - Google Patents

Abstract

FIELD: agriculture, production of growth regulator for plants. SUBSTANCE: 2-(furyl-2)-1,3-dioxanes having formula

where R¹ is H or C₁-C₄ alkyl, R² is H, C₁-C₄ alkyl, hydroxy C₁-C₄ alkyl, R³,R⁴ and R⁵ are H or C₁-C₄ alkyl is prepared by interaction of polyhydric alcohol having formula

where R¹-R⁵ are mentioned above with furfurol, molar ratio of ingredients is 1.1:1, respectively. The process is carried out at room temperature in the presence of 10 % sulfuric acid, its quantity being 10 ml per 1 mole of furfurol. Then cooling of reaction mixture and adding water into it at the beginning of crystallization are carried out to isolate desired product by cooling of aqueous suspension of emulsion. EFFECT: improved efficiency.

Description

The invention relates to organic chemistry, specifically to a method for producing 2- (furyl-2) -1,3-dioxanes having high physiological activity [1, 2] including 5-ethyl-5-hydroxymethyl-2- (furyl-2 ) -1,3-dioxane, the well-known plant growth regulator Krasnodar-I [3]
A known method of producing 2- (furyl-2) -1,3-dioxacycloalkanes based on various polyols in the presence of paratoluenesulfonic acid or calcium chloride. Moreover, the yield of the target products does not exceed 30% [4]
A known method for producing cyclic acetals of the furan series by the interaction of halogen- or nitro-substituted furfural with polyhydric alcohols in organic solvents in the presence of a KU-2 catalyst. The synthesis is carried out in an inert gas. The yield of the target products does not exceed 50 [5]
The closest solution to the problem, that is, the prototype, is a method for producing 2- (furyl-2) -1,3-dioxacycloalkanes by the interaction of furfural with polyhydric alcohols (polyols) in benzene in the presence of KU-2 ion exchanger as a catalyst [6] Let us consider it as an example of obtaining 5-ethyl-5-hydroxymethyl-2- (furyl-2) -1,3-dioxane, as a substance that has wide practical application as a plant growth regulator.

According to the prototype, a mixture of 0.1 mol (13.4 g) of freshly distilled furfural, 0.1 mol (9.6 g) of 1,1,1-trimethylolpropane, 50 ml of dry benzene and 2 g of KU-2 catalyst is boiled in a flask, equipped with a Dean-Stark trap with a reflux condenser in an inert gas flow until the evolution of reaction water ceases. The hot mixture is filtered, the catalyst is washed with a small amount of benzene. The solvent is distilled off from the filtrate. The product is isolated from the residue either by crystallization or by distillation at 180-200 ^° C (3-5 mm Hg). Yield 53%
The main disadvantages of this method.

 1. Low yield.

 2. The complexity of the hardware design process.

3. Multi-stage:
a) synthesis with stirring and heating;
b) filtration;
c) washing the catalyst;
g) atmospheric distillation of the solvent;
e) vacuum distillation or crystallization.

 5. Use of a toxic benzene solvent.

 6. Carrying out the reaction in an inert gas atmosphere.

The yield of other 1,3-dioxanes obtained by a similar method by the interaction of various homologs of propanediol-1,3 with furfural is 60-90% [7]
The aim of the invention is to increase the yield of products, simplifying the process of obtaining and separation from the reaction mixture of 2- (furyl-2) -1,3-dioxanes.

 This goal is achieved in that 2- (furyl-2) -1,3-dioxanes are prepared by reacting polyols with furfural at room temperature in the presence of an aqueous solution of sulfuric acid as a catalyst. Isolation of products from the reaction mixture is carried out by precipitation from an aqueous suspension or emulsion. The purity of 5-ethyl-5-hydroxymethyl-2- (furyl-2) -1,3-dioxane (l) after drying in air reaches 99.8% without further purification. An additional vacuum distillation is used to isolate liquid products of similar purity.

 The method is as follows.

 To a mixture of polyol with furfural, taken in equimolar amounts (1.1: 1), a 10% solution of sulfuric acid, taken in an amount of 10 ml per 1 mol of furfural, is poured at room temperature. After 5-10 minutes of vigorous stirring, the perfectly clear reaction mixture is heated and cloudy when cooled. At the time of turbidity, distilled water is added to the reaction mixture. In this case, liquid products form the lower oily organic layer, crystalline precipitate in the form of a finely dispersed precipitate.

 The crystalline product 5-ethyl-5-hydroxymethyl- (2- (furyl-2) -1,3-dioxane (l) does not need recrystallization or distillation, since it is a practically pure substance after washing and drying (99.8% The remaining 2- (furyl-2) -1,3-dioxanes are isolated by vacuum distillation of the lower organic layer of the reaction mixture, and due to the stability of the synthesized compounds, preliminary drying is not required.

 The resulting furan cyclic acetals are identified by physicochemical constants and PMR spectra.

Compared with the prototype, the claimed method is characterized in that the known reaction of the interaction of polyols with furfural, leading to the formation of 2- (furyl-2) -1,3-dioxacycloalkanes, is carried out under fundamentally different conditions: without solvent, in the presence of another catalyst - undiluted sulfuric acid instead of KU-2, at room temperature instead of the boiling point of benzene (80 ^o C). Crystalline products are isolated by precipitation from an aqueous suspension or emulsion.

 The inventive method for producing 2- (furyl-2) -1,3-dioxanes is illustrated in examples 1-14. The optimization of the synthesis process is considered in detail on the example of 5-ethyl-5-hydroxymethyl-2- (furyl-2) -1,3-dioxane (the preparation "Krasnodar-1").

Example 1. Synthesis of 5-ethyl-5-hydroxymethyl- (2-furyl-2) -1,3-dioxane (l): in a 750 ml beaker, 1 mol of molten 1,1,1-trimethylolpropane and 1 mol ( 96 g, 83.5 cm ³ ) of furfural purified by azeotropic distillation with water (volume ratio of water: furfural = 2:16, boiling point 98 ^o C). The mixture is cooled in a water bath to room temperature and 10 ml of 10% sulfuric acid solution are added in one portion with stirring. Stirring is continued for another 5-10 minutes, and as a result of the exothermic reaction of acetalization, the reaction mixture is heated to 50-50 ^o C. Subsequent cooling of the reaction mixture indicates the end of the reaction and can be accelerated by immersion of the reaction glass in a cold water bath. At the time of turbidity of the reaction mixture, indicating the beginning of crystallization of the product, 200-250 ml of distilled water is poured into the contents of the glass in one go with constant stirring. A sharp precipitation immediately begins, the degree of dispersion of which depends on the intensity of mixing. After 1 min, the reaction is complete. The reaction mixture is neutralized with a 10% sodium carbonate solution to pH 7, after which the product is filtered off under vacuum, washed several times on the filter with distilled water and dried in air at room temperature for 2-3 days. If necessary, to obtain a uniform powder, the product can be wiped manually through a sieve. Yield of 5-ethyl-5-hydroxymethyl-2- (furyl-2) -1,3-dioxane 98%
From example 1 shows that it is possible to carry out the reaction in an ordinary beaker, and not in a flask equipped with a mechanical stirrer and a Dean-Stark trap with reflux condenser. For mixing, you can use a magnetic stirrer, and in its absence, a mixer or just a plug, which does not affect the quality of the product. Carrying out the reaction at room temperature also simplifies the installation and reduces the energy consumption for the synthesis of the product. In addition, the use of the proposed method avoids the use of a toxic solvent of benzene.

 Example 2. 1 mol (96 g, 83.5 ml of furfural and 1.1 mol (147.5 g) of molten 1,1,1-trimethylolpropane is charged into a glass beaker. The reaction is carried out analogously to example 1. The product yield 95% of theoretical .

 Example 3. In a beaker loaded with 1 mol (134 g) of molten 1,1,1-trimethylolpropane and 1.1 mol (105.5 g, 92 ml) of furfural. The reaction is carried out analogously to example 1. Product yield 72%. The product has a yellowish tint.

 As can be seen from examples 2 and 3, the optimal molar ratio of the reactants is 1: 1. When using even a small excess of furfural in the reaction, the yield of the product decreases due to losses during repeated washing with hot water, necessary to remove unreacted furfural. A small excess of 1,1,1-trimethylolpropane practically does not affect the yield of the product, but is impractical for economic reasons.

Example 4. Analogously to example 1 carry out the loading of reagents. The mixture is cooled to 40 ^o C and poured 10 ml of a 10% solution of sulfuric acid. As a result of the exothermic reaction, the mixture is heated to 70 ^o C, partially resins and darkens. Yield 56%. The product has a brownish tint and cannot be removed by washing.

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

Example 5. Analogously to example 1 carry out the loading of reagents. At a temperature of 20 ^o C poured 20 ml of a 10% solution of sulfuric acid. In this case, the reaction mixture is partially resinized, the product must be purified by vacuum distillation or two to three times recrystallization. Yield 62%
Example 6. Analogously to example 1, the reagents are loaded. At a temperature of 20 ^o C poured 3 ml of a 30% solution of sulfuric acid. The reaction mixture is ground in, product yield 32%. The product has a brown tint.

 As can be seen from examples 5, 6, an increase in the amount of catalyst and its concentration leads to a gumming of the reaction mixture, a decrease in yield, and a deterioration in the quality of the product.

Example 7. Analogously to example 1 carry out the loading of reagents. At a temperature of 20 ^o C to the reaction mixture is poured 10 cm ³ 10% hydrochloric acid solution. Crystallization begins only after 35 minutes. Product yield 34%
Example 8. Analogously to example 1 carry out the loading of reagents. At a temperature of 20 ^° C., 1 cm ³ boron fluoride etherate was added to the reaction mixture. Adding water stops the onset of crystallization, the product remains in solution. Without the addition of water, the product crystallizes as a brownish solid. Yield 40%
Example 9. Analogously to example 1 carry out the loading of reagents. At a temperature of 20 ^o C poured 10 cm ^{3 of a} 10% solution of sulfuric acid. Water and a sodium carbonate solution are added to neutralize before crystallization begins. Crystallization time increases up to 50 min, product yield 25%
Example 10. The synthesis is carried out analogously to example 1. Water and a solution of sodium carbonate are poured after crystallization. The product solidifies in the form of a monolithic piece, product yield 69%
As can be seen from examples 9, 10, the optimal time of the rushing of water and a neutralizing solution, the moment of onset of crystallization.

From the above examples it is seen that the optimal molar ratio of 1,1,1-trimethylolpropane: furfural is 1: 1, the optimal amount of catalyst is 10 cm ^{3 of a} 10% sulfuric acid solution, the optimum temperature is 20 ^o C, the optimal time for adding water and a neutralizing solution is moment crystallization onset. The results of experiments 1-10 are given in table. one.

Under these conditions, a reaction of the interaction of a number of other diols with furfural was carried out. The result is 2- (furyl-2) -1,3-dioxanes with yields of 70-85%
Example 11. Synthesis of 5,5-dimethyl- (2-furyl-2) -1,3-dioxane (II): 1 mol (136 g) of molten 2,2-dimethyl-1,3 is loaded into a 750 ml beaker -propanediol (neopentyl glycol) and 1 mol (96 g, 83.5 cm ³ ) of furfural purified by azeotropic distillation with water. The mixture is cooled in a water bath to room temperature and 10 ml of 10% sulfuric acid solution are added to one prem with stirring. Stirring is continued for another 5-10 minutes, while as a result of the exothermic reaction of acetalization, the reaction mixture is heated to 40-50 ^o C. Subsequent cooling of the reaction mixture indicates the end of the reaction and can be accelerated by immersion of the reaction glass in a cold water bath. At the time of turbidity of the reaction mixture, 200-250 ml of distilled water is poured into the contents of the beaker in one go with constant stirring. The mixture is immediately divided into two layers. The reaction mixture was neutralized with a 10% sodium carbonate solution to pH 7, the layers were separated using a separatory funnel, and chromatographed. The upper aqueous layer contains virtually no product. From the lower layer, 5,5-dimethyl-2- (furyl-2) -1,3-dioxane is isolated by vacuum distillation in 75% yield (mp 20 ^° C). In this case, preliminary drying of the reaction mixture is not required, because the product is quite stable when heated.

Example 12. Analogously to example 11, the interaction of 1 mol (118 g, 115.3 ml) of 2-methyl-pendanediol-2.4 with 1 mol (96 g, 83.5 cm) of freshly distilled furfural give 2- (furyl-2) - 4,4,6-trimethyl-1,3-dioxane (III) d $\genfrac{}{}{0ex}{}{\text{twenty}}{\text{4}}$ = 1,060, n $\genfrac{}{}{0ex}{}{\text{twenty}}{\text{D}}$ = 1.4870, T _bales. = 116 (4)) with a yield of 72%
Example 13. Analogously to example 11, the interaction of 1 mol (76 g, 72.1 cm ³ ) of propanediol-1.3 with 1 mol (96 g, 83.5 cm ³ ) of furfural gives 2- (furyl-2) -1.3 dioxane (IV) d $\genfrac{}{}{0ex}{}{\text{twenty}}{\text{4}}$ = 1,206, n $\genfrac{}{}{0ex}{}{\text{twenty}}{\text{D}}$ = 1.4870 T _bp. 105 ^o C (18)) with a yield of 81%
Example 14. Analogously to example 11, the interaction of 1 mol (90 g, 89.5 cm ³ ) of butanediol-1.3 with 1 mol (96 g, 85 cm ³ ) of furfural gives 2- (furyl-2) -4-methyl-1 , 3-dioxane (V) d $\genfrac{}{}{0ex}{}{\text{twenty}}{\text{4}}$ = 1,118, n $\genfrac{}{}{0ex}{}{\text{twenty}}{\text{D}}$ = 1.4830 T _bales. = 126 ^o C (20)) with a yield of 79%
Compounds (II-V) are isolated by vacuum distillation. The results of the synthesis of compounds (II-V) are given in table. 2.

 Based on the proposed synthesis method, a simple and effective technology for the production of the active substance of the plant growth regulator Krasnodar-1 on an experimental-industrial and industrial scale can be developed. The technology can be implemented on the basis of the Scientific Research Institute of Herbicides (NITIG) on existing equipment with a slight upgrade.

Using the proposed method allows you to:
increase the yield of 2- (furyl-2) -1,3-dioxanes to 70-98%
reduce the reaction time from 2-2.5 to 0.25 hours;
replace the KU-2 catalyst with more available sulfuric acid, avoid product losses on the catalyst;
avoid the use of a toxic solvent of benzene in the reaction, replace it at the crystallization and washing stages with distilled water;
reduce the reaction temperature from 80 ^o C on the prototype (the boiling point of benzene) to room temperature, which greatly simplifies the installation and reduces the energy consumption for the production of the drug;
significantly simplify the hardware design of the process compared to the prototype, eliminate the use of expensive inert gas;
significantly simplify the process of isolating 5-ethyl-5-hydroxymethyl-2- (furyl-2) -1,3-dioxane (Krasnodar-1 plant growth regulator), eliminate the recrystallization step, and obtain a pure product that is not contaminated with resins and traces of solvent .

Literature
1. Blicke FF Anderson FFJAm.Chem.Soc. 1952, 74, p. 1733.

 2. Kulnevich V.G. Zelikman Z.I. Shkrebets A.I. CHC, 1971, p. 291.

 3. A. St. USSR N 694168.1979.

 4. Lowry D. Glycerin and glycols. L. Goskhimtekhizdat, 1933, p. 396.

 5. Shkrebets A. I. Zelikman Z.I. Kulnevich V.G. and other HGS, 1972, N 9, p. 1159.

 6. A. St. USSR N 235044, 1969.

 7. Shkrebets A.I. Abstract of diss. Candidate of Chemical Sciences Krasnodar: 1973.

Claims (1)

The method of obtaining 2- (furyl-2) -1,3-dioxanes of the General formula

where R ^{1 is} a hydrogen atom or C ₁ -C ₄ alkyl,
R ^{2 is} a hydrogen atom, C ₁ -C ₄ alkyl, hydroxy-C ₁ -C ₄ alkyl,
R ³ , R ⁴ and R ^{5 are} hydrogen atoms or C ₁ -C ₄ alkyl,
the interaction of a polyhydric alcohol of the formula

where R ¹ -R ⁵ have the indicated meanings,
with furfural in the presence of an acid catalyst, characterized in that the process is carried out at a molar ratio of components equal to 1.1 1, respectively, at room temperature in the presence of 10% sulfuric acid, taken in an amount of 10 ml per 1 mol of furfural, followed by cooling the reaction mixture and adding water to it at the time of crystallization to isolate the target product by precipitation from an aqueous suspension or emulsion.

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