SU1684282A1 - Method of synthesis of 2-oxy-1,8-cineol - Google Patents

Abstract

The invention relates to heterocyclic compounds, in particular to the preparation of 2-hydroxy-1,8-cineol, which is used for the synthesis of physiologically active substances. The goal is to simplify the process and increase the yield of the target product. The preparation is carried out by treating & b-terpineol with an equimolar amount of iodine in a medium of 23-56% by weight of an aqueous solution of potassium iodide followed by treating the resulting 2-iodine-1,8-cineole with an aqueous solution of potassium carbonate. The yield of the product is up to 37-71% (against 10% in the known method).

Description

The invention relates to an improved process for the preparation of 2-hydroxy-1,8-cyneol, which is used in the pharmaceutical industry and as an intermediate for the synthesis of physiologically active substances.

The goal is to simplify the process and increase the yield of the target product due to the use of OC-terpineol, which is subjected to, as the initial carbocyclic hydrocarbon. iodocyclic in the presence of 23-ЗЬ% - aqueous K1 solution followed by treatment of the obtained 2-iodine-1,8-cineol with potassium carbonate in an aqueous medium.

Example 1. To a mixture of 10 ma.h. alpha-terpineol, 9.5 ma. bicarone sodium and 95 parts by weight of water add a solution of iodine in potassium iodide

(16 parts by weight of iodine, 31 parts by weight of potassium iodide, 100 parts by weight of water) at room temperature and stirring for 30 minutes. The mixture was transmemulated for 2 hours, extracted with diethyl ether, the extract was treated with 5% sodium thiosulfate and MgSO4. After distilling off the solvent, 8.6 parts by weight of the remaining oil (9.7 parts by weight) was added. potassium carbonate and 100 wt.h. water. The mixture is heated at 96-100 ° C for 5 hours, washed with Lgm, extracted with diethyl ether, dried with MgSO4. After distilling off the solvent from the remaining oil (8.2 parts by weight), the fraction of 2-hydroxy-1,8-cineol (4.1 parts by weight of purity 92%) by bp was isolated by distillation. 89-90 ° C / 2 mmHg, Pr 1.4840, yield 37.2% of the theoretical amount.

Found,%: C 70.3J H 10.7.

0 8 ° Vrchsleno,%: C 70, L {H 10.70

IB

O 00 N O

uh oh

PRI me R 3. Analogously to example 1, but alpha-terpineol is treated with a mixture containing 16 wt. iodine 51 wt.h ,, potassium iodide and 1 76 mach.h. water (concentration of potassium iodide in water is 15%).

The complete conversion of alpha-terpineol to the reaction products takes 3.5 hours. After the treatment, 4.0 mph are obtained. 2-hydroxy-1,8-cyneol (purity 92%).

Pr imer4. Analogously to example 1, but the temperature of the reaction spectrum spectrum (UK-20 spectrometer, liquid film) cm 1: 790, 1045, 1168, 1370, 1387, 1460, 2975 (CH) gS 7.35, 1468 2928 (CH2), 1348 , 2880 (CH). 920, 1020 (cyclohexane), 1100 (C-O-C-C), 1078, 3440 (OH).

NMR spectrum N (spectrometer BS-567 A, 10% solution in SDS internal standard TKS) o, ppm: 1.18 with JQ (6H, 2SNE) 1.33 with (ZN, SN,), 2 , 32 s (1H, OH) 1.20-2.40 m (7H, CH, ZCHN2), 3.77 d (1H, C2H).

NMR spectrum 13C (spectrometer Bruker

WH-90 operating frequency for C 22.63 MHz.) 5 s When adding iodine in an aqueous plant, a 30% solution in the SDSS was used, an internal TMS standard with a pulse duration of 9 ms (60) and a delay between pulses of 12 s), ppm C 82.1 C6 24.6 C3 33.6 C 41.8 C 31.9. C2 82.6, C7 23.6 C3 71.8 C1 30.5, C10 28.9.

GLC analysis: LHM-8 MD chromatograph with flame ionization detector, ZmhZmm column, filled with inert AW-DMCS, granulation (0.250-0.315 mm) 5% SE-30 siloxane rubber, column temperature 130 ° C, nitrogen consumption 60 ml / min Relative retention time: alpha-terpineol 1.00; 2-hydroxy-1,8-cineole 1,88

Pr im p 2. Analogously to example 1 but alpha-terpineol is treated

20

25

The potassium iodide is maintained by ZaaC. After the same treatment as in example 1, the fraction of 2-hydroxy-1,8-cineole (3.2 parts by weight; purity 88%) was isolated by distillation.

The upper limit of the concentration (56%) of potassium iodide is due to the limiting solubility of potassium iodide in water at 20 ° C. A decrease in this concentration of less than 20% is impractical due to an unjustified increase in the volume of the reaction mixture. In addition, the processing time is increased (1.4-1.7 compared with Examples 1.2).

Increasing the temperature of the iodization process above room temperature leads to a decrease in the yield of the target product (. Example 4).

thirty

a mixture containing 16 ma.h. iodine 31 ma.ch. potassium iodide and 24 ma.ch. water (concentration of potassium iodide in water is 56%).

The complete conversion of alpha-terpineol to the reaction products takes 2 hours, including the step of adding pe-40

to alpha-terpineol. After the same treatment as in example 1, 4.2 mue.h are obtained. 2-hydroxy-1,8-cyneol (purity 93%).

Duration of the reaction, h The content of the target product in the organic layer,%

PRI me R 3. Analogously to example 1, but alpha-terpineol is treated with a mixture containing 16 wt. iodine 51 wt.h ,, potassium iodide and 1 76 mach.h. water (concentration of potassium iodide in water is 15%).

The complete conversion of alpha-terpineol to the reaction products takes 3.5 hours. After the treatment, 4.0 mph are obtained. 2-hydroxy-1,8-cyneol (purity 92%).

Pr imer4. Analogously to example 1, but the temperature of the reaction mixture WHILE iodine is added in an aqueous plant

5 si When iodine is added to an aqueous plant

0

five

The potassium iodide is maintained by ZaaC. After the same treatment as in example 1, the fraction of 2-hydroxy-1,8-cineole (3.2 parts by weight, purity 88%) was isolated by distillation.

The upper limit of the concentration (56%) of potassium iodide is due to the limiting solubility of potassium iodide in water at 20 ° C. A decrease in this concentration of less than 20% is impractical due to an unjustified increase in the volume of the reaction mixture. In addition, the processing time is increased (1.4-1.7 compared with Examples 1.2).

Increasing the temperature of the iodization process above room temperature leads to a decrease in the yield of the target product (. Example 4).

The optimal duration of the process (4-5 hours) is determined by GLC by determining the maximum conversion of the intermediate product to the desired product.

0

The dynamics of the increase in the content of the target product depending on the duration of the reaction is as follows to Example 1 o

13456 31 60 67 70 71

Thus, this method allows to simplify the process by using available tf-terpineol as the starting compound instead of prototype 2-oxocineol, as well as using available and safe iodine, iodide and potassium carbonate instead of lithium aluminum hydride. In addition, this method allows to increase the yield of the target product from 10 to 37-71%

Claims (1)

DETAILED DESCRIPTION A method for producing a 2-hydroxy-1,8-cineole based on a carbocyclic hydrocarbon derivative, characterized in that, in order to simplify the process and increase the yield of the target product, Od-terpineol is used as a derivative of the carbocyclic hydrocarbon, a treatment with an equimolar amount of iodine in the medium 23516842826 56% by weight of an aqueous solution of iodide of valuable 2-iodine-1,8-cineol were diluted with water, followed by treatment with potassium carbonate.