RU2464035C1 - Method for preparing borneol from waste fir wood green extractives - Google Patents

Abstract

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical and cosmetic industry, particularly to a method for preparing borneol. The method for preparing borneol from a hydrodistillate of a lipid portion of fir wood green extract involving saponification of the hydrodistillate in an alcohol solution of alkali, heating, stripping of alcohol and a portion of volatile ingredients, washing in hot still bottom water, separation of still bottom from an aqueous layer, crystallisation of borneol, filtration, washing in an organic solvent, re-crystallisation from mixed ethylacetate and petroleum benzene under certain conditions.

EFFECT: method is used to prepare borneol with the content of the main ingredient >99%; the method promotes a higher degree of using the feedstock.

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Description

The invention relates to methods for producing biologically active substances from renewable plant materials, specifically borneol, from waste from the extraction of green wood fir.

Borneol is of interest as a starting material for the synthesis of camphor, and is also a promising agent for medical use. For borneol, in particular, the protective effect of cerebral ischemia is known [Not, Xiaojing; Zhao, Limei; Liu, Yulan Guangdong Yaoxueyuan Xuebao, 22 (2), 171-173], antispasmodic effect [CN 1679623 A 12]. Borneol is also used in cosmetic compositions [US 7851425] and perfumes.

A known method of producing borneol from terpene fractions of green wood fir, representing fir oil [G.A. Rudakov. Chemistry and camphor technology. M .: "Forest industry", 1976, p.150]. The method includes obtaining fir oil from a fir foot by steam distillation, followed by distillation of monoterpene hydrocarbons, distillation of the residue to obtain a mixture of bornyl acetate and sesquiterpenoids in a ratio of ~ 7: 3, vacuum distillation of this mixture with release from sesquiterpenoids. In this case, a concentrate of bornyl acetate is obtained, the saponification of which is carried out with an aqueous solution of sodium hydroxide, and the subsequent separation of technical borneol by centrifugation. This method is a prototype of the proposed method.

The disadvantages of the prototype method are as follows:

- When using fir oil as a raw material, other valuable components of the woody green matter (DZ) substance of fir (triterpene acids, low-volatile neutral components, water-soluble substances) are not removed and fall into the dump with a fir foot after steam distillation.

- Fir oil, used as a raw material, is a valuable consumer product.

- Multi-stage, technical complexity, energy and labor costs of the processes used (rectification, vacuum distillation).

The objective of the present invention is:

the creation of a technological method for producing borneol from terpene fractions obtained from the processing of plant materials containing borneol or its derivatives using available standard processing equipment.

The problem is solved by the method in which a terpenic fraction containing borneol and boron acetate is used as a raw material for the production of borneol, which is a waste from the production of the amount of triterpene acids - the Novosil preparation (the sum of volatile components separated by hydrodistillation from the lipid fraction, RU 2108803, RU 2336889), which is hydrolyzed with alcohol alkali and purified crystalline borneol from impurities by filtration, washing and crystallization.

The proposed method is as follows.

The terpene fraction, which is a waste from the production of the drug Novosil (the sum of the volatile components separated by hydrodistillation from the lipid fraction, RU 2108803, RU 2336889), containing the sum of bornel acetate and borneol> 50 wt.%, A mixture of monoterpenes, sesquiterpenes, is treated with alcohol alkali, while boron acetate in the mixture is hydrolyzed to borneol. The mixture is concentrated by distillation of alcohol and volatile impurities, the residue is washed with hot water and, when cooled, borneol is crystallized. To remove non-volatile impurities, the crystals are washed with petroleum ether or gasoline, and a product with a basic substance content> 94% is obtained, which is additionally crystallized from a mixture of ethyl acetate and petroleum ether 1: 5 to obtain a product with a basic substance content> 99%.

The inventive method differs in the following:

- As a terpene fraction of fir green wood for the production of borneol, hydrodistillate from the lipid part of the extract of green wood is used (containing the sum of borneol and bornyl acetate ~ 50 wt.%) - the fraction of extractive substances from the production of Novosil, which allows for complex processing of raw materials.

- Hydrolysis of the terpene fraction containing the sum of borneol and bornyl acetate 50% + is carried out with an alcohol solution of an inorganic base.

- Purification from crystalline borneol impurities (monoterpenes, sesquiterpenes) is carried out after the hydrolysis step, in contrast to the prototype method, where fir oil boronacetate is purified from monoterpenes and sesquiterpenes before hydrolysis, which requires the use of distillation and vacuum rectification.

The advantages of the proposed method.

- The use of a hydrodistillate of a neutral fraction of the extract of woody green fir - a waste from the Novosil production to produce borneol allows to increase the degree of use of processed raw materials, reduce the amount of waste, which determines the environmental benefits of the proposed method.

- Economic benefits associated with the use of the present method as a raw material of the hydrodistillate of the lipid fraction of the extract of green wood, which is a waste from the production of the drug "Novosil", while fir oil used by the prototype method is a finished consumer product.

- Technological advantages of the proposed method are associated with the use of purification of a crystalline product of borneol by washing and crystallization, while the prototype method uses technically complex and energy-intensive vacuum distillation and distillation of fir oil bornyl acetate before saponification, as well as centrifugation of the product after saponification.

The inventive method is illustrated by example.

Example. The combined fractions of the hydrodistillate from the sum of lipids obtained according to [RU 2108803, RU 2336889], with a total content of borne acetate and borneol of at least 50 wt.% In the amount of 50 kg, are loaded into a steel enameled apparatus with a capacity of 100 l, equipped with a mechanical stirrer and a heating jacket, and add 20 kg of an alkaline alcohol solution containing 15% potassium hydroxide and 80% ethanol. The mixture of reagents is heated to a temperature of 50-60 ° C by supplying hot water or steam to the jacket of the apparatus and incubated for ~ 1 hour with stirring.

The end of saponification of boronyl acetate is monitored by TLC on Silufol or Sorbfil plates. Eluent is a mixture of 20% ethyl acetate and 80% petroleum ether or hexane. R _{f of} borneol acetate is 0.63, R _{f of} borneol is 0.36. The developer is concentrated sulfuric acid (raspberry stain after heating the plate) or a 3% solution of vanillin and sulfuric acid in ethanol (staining after heating the plate: light brown - borne acetate, bluish - borneol).

Alcohol and part of the volatile hydrolysis products (~ 25-30 kg) are distilled off at a temperature of 40-60 ° C in a technical vacuum (0.2-0.3 ata). The hot bottoms are washed in the apparatus with hot tap water (4 times 10 l), each time mixing the mass for 1-2 minutes. Washing is stopped when the pH of the aqueous layer reaches 7-8. After sedimentation, the lower aqueous layer is drained for 10-15 minutes, then 30-33 kg of bottoms liquid with borneol content up to 70% (yield 85-90% of theoretical).

продукта до перекристаллизации (содержание основного вещества >94%) составляет - 34±3° (с=40-50 мг/см³, в ЕOtН, лит. данные: - 35.6°), после перекристаллизации (содержание основного вещества >99%) - -37.0±0,5°.Crystallization upon cooling the still liquid (melt) to a temperature of 0 ÷ (-7) ° С gives crude borneol (content of the main substance> 85%) as a light yellow crystalline substance, followed by separation of the liquid phase containing impurities by filtration on a suction filter in a technical vacuum. Technical borneol (content of the main substance> 94%) is obtained by washing the crude product on the suction filter with petroleum ether or gasoline with a yield of 72.4-74.3% of theory based on the content of boron acetate in the saponified mixture, or 10-15% based on the amount of extractive substances DZ fir, or 1.0-1.5% by weight of air-dry DZ fir. The liquid phase, separated by filtration from crystalline borneol on a suction filter, and one stripped off gasoline washing solutions are accumulated and used to obtain additional quantities of the target product. The product is colorless or slightly yellowish plate crystals, sparingly soluble in water (0.075 g / 100 ml), but readily soluble in most organic solvents - hexane, tert-butyl methyl ether, alcohol, isopropanol, acetone, ethyl acetate. Specific rotation angle

product before recrystallization (content of the main substance> 94%) is - 34 ± 3 ° (c = 40-50 mg / cm ³ , in ЕOtН, lit. data: - 35.6 °), after recrystallization (content of the main substance> 99%) - -37.0 ± 0.5 °.

Borneol with a basic substance content> 99% is obtained in 72.0% yield by recrystallization of a technical product from a mixture of ethyl acetate and petroleum ether (1: 5). ¹ H NMR spectrum (in CDCl ₃ ) δ 0.81, 0.82 and 0.83 ppm, all 3H singlets (three CH ₃ groups); δ 3.96 ppm, 1H, ddd, J = 10.0, 3.4 and 1.6 Hz, ( Н -С-ОН), characteristic of endo-borneol. The dry residue obtained after removal of the solvent mixture from the mother liquor contains 40-50% borneol, which can be isolated in additional yield up to 20% by weight of the dry residue.

Claims (1)

A method of obtaining borneol from a hydrodistillate from the lipid part of an extract of green wood fir containing a sum of 50% by weight of borneol and boronyl acetate, a mixture of monoterpenes, sequiterpenes, including saponification of a hydrodistillate with an alkaline alcohol solution (15% KOH and 80% ethanol), heating to 50-60 ° C, keeping for 1 h with stirring, distilling off the alcohol and part of the volatile components, washing with water the hot bottoms to reach pH 7-8, separating the bottoms from the water layer, crystallization of borneol, filtering, washing with organic recrystallization from a mixture of ethyl acetate and petroleum ether (1: 5).