Method of production of limonene diepoxides

FIELD: chemistry.

SUBSTANCE: invention covers production of mixture of stereoisomers of limonene diepoxides (1.2-8.9-diepoxide-p-terpanes) used as resin components or composites for technical purposes, in fine organic synthesis and in perfumes. The method includes epoxidation of double bonds in limonene with diluted hydrogen peroxide in water solution of acetonitrile, N,N-dimethylformamide or methanol at ambient temperature under catalytic action of manganese sulphate mixed with sodium bicarbonate and salicylic acid. Further reaction products are extracted from the reaction mixture with organic solvent, extractant is distilled. Crude epoxide thus obtained undergoes purification by established methods (vacuum distillation or absorption). The method allows to obtain diepoxides mixture with 93-97% purity and yield up to 85%.

EFFECT: development of technological method of production of resin component and composite material for fine organic synthesis.

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The invention relates to the field of chemistry terpene compounds, namely, to obtain a mixture of spatial isomers diepoxides limonene - 1,2-8,9-diepoxy-para-montanov General formula I

Compound I can be used as an additive to lubricating oil for refrigerators [US 5454963, 1995], as well as the starting compound to obtain hernandulcin - substance, which is 1000 times sweeter than cane sugar [Kenji Mori, Minoru Kato. Tetrahedron Letters, 1986, 27, 981]for the stereoselective synthesis of components of the sex pheromone of the southern green activist [Chen Xin, Gottlieb Levi, Jocelyn Millar G. Synthesis, 2000, No. 2,269].

Diepoxide limonene is also widely used as components of resins and composite materials. For example, to obtain a thermosetting resin, insulating semiconductor products [WO 0174798, 2001], a lubricating composition for optical fiber [EN 2155169, 2000], for the manufacture of cosmetic compositions [US 2006 52,521, 2006], compositions for applying glossy coatings on ceramics, glass and porcelain [DE 10328531, 2005].

From literature it is known that diepoxide limonene extracted from the products of the epoxidation of limonene.

Sequential epoxidation of double bonds in the molecule limonene is not practiced, so the higher the content of diepoxides in the epoxidation products, the more efficient the process and the receipt.

All known methods of epoxidation of limonene are divided into two groups: using as epoxidised agent aqueous hydrogen peroxide and using other sources of active oxygen.

The methods of the second group of ethnologica, since they use expensive, unstable, suitable only for laboratory conditions oxidants [WO 0174798, epoxygenase agent - m-chlormadinone acid], or complex and expensive catalysts, sometimes in the presence of auxiliary substances [Naima Fdil, My Youssef Ait Itto, Mustapha Ait Ali et al. Tetrahedron Letters, 2002, 43, 8769, epoxygenase agent with oxygen in the presence of isobutyl aldehyde, the catalyst is a complex of ruthenium - p-timal with 1,2,4-thiazepine as ligands. The content of diepoxides in raw 60%]. Besides, at the stage of obtaining raw these methods often give a lot of monoepoxides.

Variants of using hydrogen peroxide, can, in turn, be divided into four groups depending on the catalytic system. The main component of this system may be a simple chemical structure, but expensive and difficult, which is, for example, methyltrioxorhenium (MTO), which gives good results epoxidation [PCT WO 98/33786, 1997; US 5939568, 1999]. The second group of methods uses toxic or harmful to the environment catalysts, such as dibutylphthalate [Michiel S. van Vliet,Isabel W..E. Arends, Roger A. Sheldon Tetrahedron Letters, 1999, 40, 5239]. So get monoepoxide containing up to 5% of diepoxides. In the third group of methods are used cheap and available catalysts, which require, however, either hydrogen peroxide of high concentration, or give little diepoxides. For example, in [Michiel S.A. van Viet, Dalmo Mandelli, Isabel W.C.E. Arends et al. Green Chemistry, 2001, 3, 243] in addition to the Al₂O₃use 60%hydrogen peroxide, disutility ether, ethyl acetate, a nitrogen atmosphere.

Recently, a number of options catalyzed epoxidation of olefins, including lemon, using complex manganese complexes with nitrogen-containing macrocyclic ligands, for example, trimethyltetradecylammonium, as well as complexes containing heteroalicyclic, ion-exchange resins, mesoporous silica with grafted thereon a titanium atoms. The lack of such methods of epoxidation is not only complex catalyst, but not high (no higher than 30%) content of diepoxides in the reaction products, and the use of ancillary reagents. For example, in [Dmandell, Kubowitzki, Usuard and other Chemistry of natural compounds, 2002, No. 3, 203] use complex [L₂Mn₂O₃](PF₆)₂with the addition to the reaction acetic acid medium, where L is 1,4,7-trimethyl-1,4,7-triazacyclononane; output epoxides 48% content diepoxides 25%.

In kachestvenaia selected epoxidation of limonene action 35%aqueous hydrogen peroxide in the presence of methyltrioxorhenium (MTO), most are described in detail in [Aida L. Villa de P., Dirk E. De Vos, Consuelo Montes de C. et al. Tetrahedron Letters 1998, 39, 8521]. To achieve good results diepoxides process is carried out with 2,6 - or 3,4-multiple excess aqueous hydrogen peroxide content of the catalyst is 0.5 mol.% in the presence of pyridine. When more of these excess hydrogen peroxide to the pyridine add methylene chloride, with less excess - 3-cyanopyridine. The duration of the reaction to achieve 100%conversion of limonene and 90%selectivity to diepoxides amounted to less excess hydrogen peroxide for 6 hours at 20°S, with a larger excess of hydrogen peroxide - 40 hours at 0°C. the Output diepoxides not specified.

The disadvantages of the described method include the fact that the catalyst (methyltrioxorhenium) remote and roads, and used nitrogen-containing solvents are toxic and have a sharp odor.

The present invention is to develop a technological and economical method of producing diepoxides limonene.

Chemical-physical scheme of solving the problem involves the gradual interaction of limonene with hydrogen peroxide in a medium consisting of an organic solvent (acetonitrile, N,N-dimethylformamide or methanol) and a catalyst system consisting of manganese sulfate, salicia the Oh of the acid, water, sodium bicarbonate. Next, the reaction mixture is processed by the known methods, the main of which is recovered by methylene chloride or non-polar solvent of the reaction products. After removal of the extractant epoxide raw if necessary, cleaned one of the known methods (vacuum distillation, fractionation on silica gel). The outputs of the mixture of diepoxides reach 55-85%. Organic solvents and extractants can be re-used.

Applying the above catalytic system containing manganese sulfate, sodium bicarbonate and salicylic acid, for epoxidation of limonene are not described in literature. It is the combination of the catalytic system, manganese sulfate, salicylic acid and sodium bicarbonate allows you to get diepoxide limonene with high output.

The advantage of the proposed method of obtaining diepoxides limonene is that the formation of two oxirane rings, including hard epoxidizing double bond C8-C9 molecule limonene, is produced by a simple, industrially available, non-toxic reagents under mild conditions. This is achieved by replacing methyltrioxorhenium - expensive connections received by a multi-stage synthesis from multiple element rhenium, available manganese complex catalyst. Eseade advantage of the proposed method - this is its variability, the ability to choose the most beneficial for specific conditions and costs, scale of production solvent and method of cleaning product. A further advantage of the method of using a catalytic system containing manganese sulfate, sodium bicarbonate and salicylic acid is the possibility of enrichment of diepoxides defined spatial isomers (see example 7).

The invention is illustrated by the following examples.

Example 1. The mixture of diepoxides limonene in an aqueous solution of acetonitrile.

In a glass reactor with mechanical stirrer, thermometer and fittings for loading of solid and liquid reagents pour 3.21 g (22.4 mmol) of 95%limonene, fall asleep 0.066 g (0.44 mmol) of anhydrous manganese sulfate, 0.122 g (0.87 mmol) of 98%salicylic acid, fill in 41 ml of acetonitrile. Within 3.5 hours served in the reactor cooled mixture of 30 ml of a 0.4 molar aqueous solution of sodium bicarbonate and 21.5 ml of 33%aqueous hydrogen peroxide. The temperature in the reactor 20±2°C. Stir the mixture at this temperature for another 15 minutes. Evaporated reaction mixture in vacuum at 25°With, reducing its mass 1.5 times. The distillate is collected in a cooled trap. One stripped off, the reaction mixture was treated several times with methylene chloride, the extract washed with water, dried, othona the t extractant under reduced pressure and a temperature of 25° C. Obtain 3.43 g of product containing according to GC and¹H NMR 95% of a mixture of four spatial isomers of 1,2-8,9-diepoxy-p-montanov. The signals in the spectrum of¹H NMR: 1.10, 1.11, 1.12, 1.13 (¹⁰H₃); 1.19 (⁷H₃); 2.34-2.50 (m⁹H₂); 2.82-2.92 (m²H). Output 100%diepoxide limonene per 100%lemon amounted to 86% of theoretical yield of a technical product 1.12 g per 1 g of 100%limonene. Distilled from the reaction mixture is azeotropic mixture of acetonitrile with water and distilled from a solution of epoxides methylene chloride can be used in the following cycles get diepoxides limonene.

Example 2. The mixture of epoxides limonene, enriched diepoxide, (epoxide raw) in an aqueous solution of acetonitrile using azeotropic mixture of acetonitrile - water.

In the reactor described in example 1 is placed 3.25 g (22.7 mmol) of 95%limonene, 0.067 g (0.44 mmol) of anhydrous manganese sulfate, 0.126 g (0.89 mmol) of 98%salicylic acid, pour 20 ml of acetonitrile with a water content of 4%, 20 ml of acetonitrile recovered from example 1 in the form of an azeotropic mixture with water and contains 16% water. For 2.8 hours served in the reactor cooled mixture of 30 ml of a 0.35 molar aqueous solution of sodium bicarbonate and 21 ml of 33%aqueous hydrogen peroxide. The temperature in the reactor 20±2°C. Paramashiva the t mixture at this temperature for another 20 minutes. Evaporated reaction mixture and process the rest of the suspension as described in example 1, using for the extraction of the reaction products methylene chloride, distilled in example 1. After distillation from the extract of methylene chloride obtain 3.17 g of a mixture of organic products containing according to GC 0.03% limonene, 4% monoepoxides and 67% of diepoxides limonene, and unidentified impurities. The distillate from the reaction mixture detected 2.4% limonene. Trace amounts of limonene and diepoxides there are also driven into the methylene chloride. The outputs taken lemon, expressed in the same way as in example 1, was 3% for mono - and 49% diepoxide. The outputs on the spent lemon 4% and 62%, respectively. Output technical product 1.02 g per 1 g of 100%limonene.

Example 3. Getting epoxide raw in aqueous solution of N,N-dimethylformamide (DMF).

In the conditions of example 1 when loading 3.28 g (22.9 mmol) of 95%limonene, 0.07 g (0.46 mmol) of anhydrous manganese sulfate, 0.129 g (0.92 mmol) of 98%salicylic acid, 42 ml of DMF with a water content of 0.6% and a gradual uploads to specified reagents cooled mixture of 31 ml of a 0.4 molar aqueous solution of sodium bicarbonate with 22 ml of 33%aqueous hydrogen peroxide surgery epoxidation. The reaction mass is treated with hexane, the extract washed with water, dried and after evaporation of the solution is a dye receive 2.29 g of the mixture, containing according to GC 2% limonene, 13% of monoepoxides and 84% of diepoxides limonene. The outputs of mono - and diepoxides limonene 8% and 50%, respectively. Output technical product 0.73 g per 1 g of 100%limonene.

Example 4. Getting epoxide-raw water-methanol solution.

In the conditions of example 1 when loading 3.00 g (21.0 mmol) of 95%limonene, 0.065 g (0.43 mmol) of anhydrous manganese sulfate, 0.119 g (0.84 mmol) of 98%salicylic acid, 38 ml of anhydrous methanol and gradual uploads to specified reagents cooled mixture of 29 ml of a 0.35 molar aqueous solution of sodium bicarbonate with 20.5 ml of 33%aqueous hydrogen peroxide surgery epoxidation. From the two-phase reaction mass separating the upper organic layer (1.15 g), washed with water, dried. The lower layer is evaporated and treated the same way as in example 1, obtaining after evaporation of the methylene chloride 0.97 g epoxidation products. According to GC in the upper layer contains 40% limonene, 20% of monoepoxides and unidentified impurities, which are included in the product composition of the lower layer along with limonene (3%) and diepoxide (68%). The outputs on the spent lemon: monoepoxides 10%, diepoxides 24%. 1 g of 100%limonene obtain 0.74 g of a technical product.

Example 5. Vacuum distillation of resin raw.

The mixture of products of epoxide raw synthesized in experience is Oh, similar to those described in examples 1-3, is subjected to distillation at a residual pressure of 3 mm Hg of the bulb with the neck of the nozzle without capillary. In the scheme of acceleration establish a cooled trap. The initial mixture contains 89% of diepoxides, 9% of monoepoxides and 1% limonene. To a temperature in the bath 90°With distilled compounds condensed in the trap. According to GC it's basically a mixture of limonene and monoepoxides mixed with diepoxides. To 100°With distilled fraction 1, containing the remains of limonene, 35% mono, 56% of diepoxides. Up to 120°With distilled off diepoxide (fraction 2). Set in the flask capillary and at a residual pressure of 5 mm Hg is distilled off until a temperature of 160°volatile products (fraction 3). Fractions 1 and 3 is subjected to re-distilled at a residual pressure of 3 mm Hg From a fraction of 1 at a temperature of 76-78°With distilled off one third of the mass, and the residue is combined with fraction 2. From fraction 3 at temperatures up to 110°With a few drops of distilled liquid, connecting them to the faction 2. Of 10.49 g original mix get 7.17 g of the target product, containing 94% of diepoxides, 3% monoepoxides and unidentified compounds, and 0.21 g of a mixture of 80-85% enriched monoepoxide, 0.85 g of the oligomeric epoxides and 0.88 g pitched VAT residue.¹H NMR spectrum of the target product corresponds to the range of mixture 4 stereoisomeric of diepoxides. O the d of the target product in the distillation of 72%. The total output of 100%diepoxide spent on lemon 45%, the yield of technical product 0.94 g/year

Example 6. Vacuum distillation of resin raw.

The mixture of products of epoxide raw synthesized in experiments similar to those described in examples 1-4, is subjected to distillation at a residual pressure of 2-3 mm Hg from a flask without capillary with a reflux condenser, with 11 degrees of contact of phases, and a refrigerator cooled by water. In the scheme of acceleration establish a cooled trap. The initial mixture contains 88% of diepoxides, 0.5% monoepoxides and unidentified impurities. At temperatures in the cube up to 50°With distilled products, condensed in the trap. To a temperature in the cube 140°in pairs to 81°With distilled fraction 1, to a temperature in the cube 154°in pairs to 87°With distilled fraction 2. Put the capillary and to temperatures in the cube 160°With, in pairs up to 82°With distilled fraction 3. Similar composition (GLC) fractions 1-3 unite in the target. Of the bulb with the neck of the nozzle is evaporated from the cube, a small amount of oligomeric epoxides containing ˜30% of diepoxides. As a result of 10.04 g of a mixture of products of epoxide raw get 7.53 g of the target product containing 96% of diepoxides, 0.5% monoepoxides and small amounts of unidentified compounds, and 0.09 g of a mixture containing mainly monoepoxide, 0.62 g of the oligomeric epoxides is 1.49 g of resin VAT residue. ¹H NMR spectrum of the target product corresponds to the range of mixture 4 stereoisomeric of diepoxides. The yield of the target product in the distillation of 82%. The total output of 100%diepoxide spent on lemon 45%, the yield of technical product 0.73 g/g

Example 7. Cleaning epoxide raw sorbent.

In a column with an inner diameter of 11 mm fall asleep 22.5 g of silica gel L40/100 Silasorb 600. On the post sorbent height 43 cm put 743 mg of the mixture of products of epoxide raw synthesized in experiments similar to those described in examples 1-3, containing 85% diepoxide limonene, 2% monoepoxides and unidentified impurities. The sorbate elute diethyl ether. Collect the fractions containing 62-95% of diepoxides, evaporated the solvent at room temperature and reduced pressure, receive 594 mg of a mixture containing 539 mg (91%) of diepoxide, trace amounts of monoepoxides, unidentified impurity. 370 mg of this product chromatografic on a column with an inner diameter of 8 mm under the same conditions, getting 331 mg of the target product containing 97.0-97.5% diepoxide limonene, free from monoepoxides (GC, NMR). Stereoisomeric 1,2-8,9-diepoxy-p-mentary present in the following proportions: 1S, 2R, 4R, 8S : 1S, 2R, 4R, 8R : 1R, 2S, 4R, 8S : 1R, 2S, 4R, 8R=1.4 : 1.0 : 2.0 : 1.5. Output 100%-s epoxides when cleaning 82%, the output from theoretical 100%lemon 55%, the yield of technical p is oduct 0.7 g per 1 g of 100%limonene.

The method of producing diepoxides limonene General formula I

by reacting limonene with aqueous hydrogen peroxide in the environment of a solvent and in the presence of a catalytic mixture, characterized in that the catalytic mixture using manganese sulfate in combination with sodium bicarbonate and salicylic acid at room temperature, and the solvent used polar solvent (methanol, N,N-dimethylformamide or acetonitrile).