CS271986B1 - A method of preparing verbenone - Google Patents

Abstract

Verbenone 4,6,6-trimethyl-bicyclo-(3,1,1)-hept-3-en-2-one is a component of some essential oils and is used as a component of perfumes and as an intermediate for the preparation of various aromatic terpene compounds. Verbenone is prepared by oxidation of alphapinene with oxygen in the presence of a catalyst and initiator at a temperature of 50 to 80°C for 4 to 12 hours. The essence of the solution is that the reaction takes place in the presence of 0.005 to 0.1 mol of a copper complex with the composition Cu:Br:pyridine 1:2:2 of the dipyridyl-copper-dibromide type as a catalyst, preferably and 0.001 to 0.005 mol of copper phthalocyanine or a chromic salt of carboxylic acids with a carbon number of 14 to 18 as of co-catalyst per 1 kg of alpha-pinene. The initiator is peroxide compounds or azobisisobutyronitrile.

Description

The invention relates to a process for the preparation of verbenone.

Verbenone (4,6,6-trimethyl-bicyclo- [3,1,1] -hept-3-en-2-n) is a component of some oils and is used as a component of perfumes as well as an intermediate for the preparation of various aromatic terpene compounds. Optically active (S) -cis-verbenol and (R) -cis- were found.

-verbenol are important compounds useful as components of pheromones for bark beetles and, in addition, influence the behavior of some species of harmful insects. These compounds are prepared by reduction of verbenone, which thus becomes an important intermediate in their production.

Verbenone, (4,6,6-trimethyl-bicyclo- (3,1,1) -hept-3-en-2-one), is prepared by oxidation of alpha-pinene in various ways. By oxidation and lead acetate in acetic acid with the advantage of high yields but with the disadvantage of its toxicity as well as with the problems of waste treatment -,

Mori, K .: Agr. Biol. Chem. 40, 415-0 (1976), CA 04, 135842. Oxidation in benzene and basic media is also possible and the trans-verbenol obtained after reoxidation with chromium oxide in pyridine gave verbenone - Mitsubishi Chem. In. What. Ltd .: 3ap. vykl, spis Bl 30, 940, CA 95, '

150956. Oxidation by lead dioxide, chromium oxide or ,! manganese dioxide is possible in pyridine, acetone, benzene or even ligroine - Iglesias 0., Oora I.A., Retamar J.A .: Essenze Deriv. Agrum. 42, 41-7 (1972), CA 77, 164860. Oxidation with oxygen at temperatures up to 100 ° C without catalyst gave the products alpha-pinene oxide, trans-verbenol and verbene - Moore RN, Golumbic C., Fisher, GS: J. Amer. Chem. Soc. 28, 1173-6 (1956). Similar to air oxidation at 60-90 ° C, verbenol and verbenon were obtained in addition to cosmetic products - Rain J.P., Booth A.0., Klein E.A. (Glidden Co./): U.S. Pat. 2,063,082 (1950), CA 53, 8194. At temperatures above 50 DEG C., relatively many by-products, mainly bituminous products, are formed, at 50 DEG C. the desired products are obtained as before but in better yield - 0ain J.P., Garv W.Y. (Glidden Co./): U.S. Pat. 2,911,442 (1959), CA |

55, 607. By oxidation with oxygen at a temperature of 40 [deg.] C. in the presence of oleate or cobalt stearate or of manganese as a catalyst, verbenone was obtained in a yield of up to 40% - Suzuki K .: Bull. Inst. Phys. Chem. Res. (Tokyo): 14, 179-81 (1935), CA 29, 5830. Oxidation with oxygen at 30-40 ° C in the presence of benzaldehyde and cobalt acetate as catalyst gave verbene in 40% yield - Romanichin AM, Popova NI, Prudnichenko EK: Chim. Chem. technol. 20, 177-9 (1977). By oxidation with oxygen at a temperature of 60 to 65 ΐ in the presence of pyridine and cobalt palmitate as catalyst, verbenone was obtained after reoxidation with chromium oxide in a yield of 33% - Kalvoda L., Vrkoč L .: Pat. Czechoslovakia AO 215485/1982 /. By modifying the process using dibenzoyl peroxide as initiator or peracetic acid, verbenone was obtained in a yield of up to 40%, while the reaction time was shortened from 24 to 18 hours - Collective: Pheromones, research report, VÚCHT Bratislava 1983. Autooxidation with oxygen at 25 ° C for in the presence of cobalt naphthenate as catalyst, a mixture of verbenol and verbenone was also obtained - Bohe RL: Essenze Deriv. Agrum. 52, 148-56 (1983), CA 101, 211401. Oxidation with oxygen or air at 50 DEG C. for 20 hours in the presence of a dipyridyl diiodide complex as catalyst gave verbenone in good yield above 30% - bhaduri S., Mahadru M.M. / Indian Explosives Co./: Brit. pat. 2,078 th most common .223 (1982), CA 96, 218066. Oxidation of oxygen in chlorobenzene in the presence of palladium chloride and meonium chloride as catalysts with the addition of substances such as lithium, sodium, potassium and barium chlorides gave verbenol and verbenone in a yield of up to 57%. Sirakova V., Dimitrov 0., Angelov V .: Docl. Bolg. Akad. Nauk 22, 767-9 (1984), CA 101, 211484. By oxidation at temperatures of 68 to 80 ° C, it is possible to increase the yield of products as well as larger products for cosmetics in addition to increasing the conversion - Dimitrov 0., Sirakova V., Angelov V., Stefanova R .: Chim. Ind. / Sofia /: 56, 54-56 / 1984 /, Ca 101, 38676, similar to Sirakov

V.) Dimitrov 0 .: Chim. Ind. / Sofia / 52, 205-7 / 1987 /, CA 108, 211898. | i

Oxygen oxidation at 80 ° C using azodisobutyronitrile (AIBN) as initiator also yields verbenone - Pritzkow W. in addition to cosmetic products.

CS 271986 Bl.

Van Trien V., Schmidt-Renner W .: Miltitzter Berichte 80, 17-25. Oxygen oxidation at 70-80 ° C using AIBN as an initiator yielded verbenone, among other products, with the main purpose being kinetic measurements and design of probabilities. reaction mechanism - Martinez de la Cuesta P.O., Rus Martinez E., Garcia Herruzo F .: Ann. Quim., Ser. A, 80, 262-6 (1984). Oxidation with oxygen at 50-80 ° C for 4-12 hours in the presence of dipyridyl dibromide-cobalt as catalyst and AIBN or organic peroxides as initiators gave a mixture with a yield of 34% verbenone and 10% verbenol, after reoxidation with chromium-sulfur mixture up to 90% verbenol transformed into verbenon - Kizlink 3., Hronec M., Cvengrošová Z., Kuruc ú., Kříž M., Obložinský A., Ilavský 3 .: Pat. ČSSR AO 258634/1988 /, by adding chromium salts of carboxylic acids as cocatalysts it is possible to further increase the amount of obtained oxidation products - Kizlink 3., Hronec M., Cvengrošová Z., Haruštiak, M., Obložinský A., Hutník 3., Ilavský 3rd: USSR (PV 7113-87 .. A0 .....)

Although the oxidation of alpha-pinene by means of tetravalent lead salts or even trivalent salts of thallium is advantageous in terms of product yields, it is disadvantageous from the point of view of the high toxicity of the reagents and thus of the waste disposal problems. Oxidation in alkaline environment by salts of cobalt or manganese so-called metal soaps are good and products are obtained at the time of extraction, but a relatively large amount of harmful organic bases such as pyridine, quinoline, target, amines and the like. In addition to unpleasant work, they also cause more demanding health protection for workers. In some processes, there is also considerable economic complexity caused mainly by waste disposal and operation of technological equipment.

These shortcomings are partially overcome by the process for preparing verbenone from alpha-pinene by oxidation with oxygen in the presence of a catalyst at 50 to 80 ° C for 4 to 12 hours according to the invention, which is carried out in the presence of 0.005 to 0.01 mol. of a methanate complex of Cu: Br: pyridine 1: 2: 2 type of dipyridyl-meadibromide type, as a catalyst, and preferably 0.001 to 0.005 mol of copper phthalocyanine or chromium salt of carboxylic acids having a carbon number of 14 to 18 as cocatalyst. The reaction can also be carried out in the presence of a solvent of a meonate complex catalyst such as carboxylic acids or their esters. The reaction takes place in the presence of azobisisobutyronitrile or organic peroxide compounds as initiators. The reaction mixture obtained is distilled by distillation into a fraction containing mainly unreacted pinene, which can be recycled, and into a fraction of oxidation products containing mainly oxygenated morioterpenes, from which verbenon and trans-verbenol can be obtained in relatively good purity by distillation in vacuo. up to 85% for further processing e.g. reoxidation of trans-verbenol naverbenon and the like. The fraction of oxidation products can be reoxidized in an acid homogeneous medium with peroxyacetic acid or a mixture of acetic acid and hydrogen peroxide with the addition of sulfuric acid, catalyzed by cobalt salts at temperatures of 60 to 90 ° C with the addition of alkali bromides. In this process, trans-verbenol is oxidized to verbenone and this can then be obtained from the mixture by rectification under vacuum in a very good purity of 87 to 97%, which is sufficient for its further processing by reduction to the desired cis-verbenol for pheromones.

The range of temperatures used in the oxidation of pinene is 30 to 90 ° C, preferably around 55 to 65 ° C. At lower temperatures less by-products are formed, but the reaction time is too long, at higher temperatures the elongation of by-products, mainly of a bituminous nature, is already considerably high and above 80 ° C their formation is practically unbearable, these proportions causing great difficulties in working up the reaction mixture. Removal of the water of reaction by suitable equipment has a favorable effect on the course of the reaction. The reactor must also have a considerable reserve space for considerable foaming of the oxidized pinene, namely 30 to 50% of the height of the pinene column in the batch.

The copper complex catalyst used can be prepared relatively easily according to King's cars. H.C.A., Koros E., Nelson S.M .: 3. Chem. Soc. 1963, 5449 originally intended for

CS 271986 B1 cobalt and with the possibility of its application also for meth), by precipitation of a hot solution of meononium bromide in butanol with a solution of pyridine in butanol. Chromium salts, in turn, are precipitated by hot solutions of sodium salts of carboxylic acids with a solution of inorganic chromium salts. Carboxylic acids with a carbon number of 14 to 18 are particularly preferred here.

Deperoxidation of the reaction mixture after oxygen oxidation can be done thermally by heating the mixture at 110 ° C for 30 minutes or passing it through a heated packed column or by catalytic heating to 90 ° C with the addition of 1 to 3% by weight of boric acid by weight of the mixture during 30 minutes. The acid remains in the distillation residue after distillation.

Example 1

500 g of alpha- pinene (97% purity by GLC). After heating the contents of the reactor to 90-100 ° C, the oxygen flow was maintained between 20-30 lh ^-1 and 2.2 g (0.005 mol) of a finely divided dipyridyl-meromobromide (Py ₂ CuBr _{2) catalyst were gradually added to the top of the reactor.} ). After about 10 minutes, when most of the catalyst had dissolved, the temperature was adjusted to 60-2 ° C and the oxygen flow to 20 lh ^-1 , a further 0.8 g (0.005 mol) of azobisisobutyronitrile (AIBN) was added as initiator. The mixture was oxidized for 6 hours, allowed to cool to about 30 ° C, filtered and then maintained at 90 ° C for at least 30 minutes with the addition of 2% boric acid with stirring in a conical flask to destroy the peroxides present. After cooling, the reaction mixture was partitioned under vacuum at a pressure of about 2.66 kPa (20 torr) into two fractions, fraction I up to 70 ° C (which contains predominantly unreacted pinene that can be recycled) and fraction II. to a flask temperature of 180 ° C, which contains oxidation products, mainly verbenone and trans-verbenol. The distillation residue contains various bituminous substances and catalyst residues. Fraction II. was then rectified under vacuum using an 8 TP injection column. A total of 250 g of unreacted pinene (fraction I) and 105 g (24.7%) of oxidation products (fraction II) were obtained, from which 39 g (37%) of verbenone and 17.6% of verbenol were obtained, the residue being 50 g (29%) to reacted pinene. The conversion was 42% and the selectivity 0.31.

Example 2

As in Example 1, a pinene charge was used and a catalyst was added at 90-100 ° C, 2.2 g (0.005 mol) of Py ₂ CuBr ₂ and at 60 ° C an initiator of 1.2 g (0.005 mol). ) of dibenzoyl peroxide and the oxidation was carried out for 6 hours, then the reaction mixture was worked up as in Example 1. 240 g of unreacted pinene (fraction I) and 130 g (26.5%) of oxidation products (fraction II) were obtained, from which 32 , 6 g (25.1%) of verbenone and 24.0 g (18.5%) of verbenol. The conversion was 51% and the selectivity 0.21.

Example 3

As in Example 1, a pinene charge was used and a catalyst of 2.2 g (0.005 mol) of Py ₂ CuBr ₂ and a cocatalyst of 0.8 g (0.001 mol) of chromium palmitate and 50 g (0.001 mol) were added at 90-100 ° C. g of acetic acid and at 60 DEG C. an initiator of 0.8 g (0.005 mol) of AIBN and the oxidation was carried out for 5 hours, then the reaction mixture was worked up as in

OS 271986 B1 of Example 1. 270 g of unreacted pinene (fraction I) and 80 g (16.3%) of oxidation products (fraction II) were obtained, from which 33.3 g (41.6%) of verbenone and 19 , 1 g (23.8%) of verbenol. The conversion was 45% and the selectivity 0.22.

Example 4

As in Example 2, a pinene charge was used and a catalyst of 1.1 g (0.0025 mol) of Py2CuBr2 and a cocatalyst of 1.6 g (0.0025 mol) of copper phthalocyanine were added at 90-100 ° C and 50 g of butyl acetate and an initiator at 60 DEG C., 1.2 g (0.005 mol) of dibenzoyl peroxide, and the oxidation was carried out for 8 hours. The reaction mixture was then worked up as in Example 1. 220 g of unreacted pinene (fraction I) and 160 g (32.6%) of oxidation products (fraction II) were obtained, from which 40 g (25%) of verbenone and 30 g of 8 g (19.3%) of verbenol. The conversion was 48% and the selectivity was 0.28.

Example 5

100 g of fraction II (0.25 mol of trans-verbenol) and 100 g of acetic acid were weighed into a 1000 ml conical flask with stirrer and thermometer. 6.3 g (0.0025 mol) of cobalt acetate tetrahydrate and 5 g (0.05 mol) of sodium bromide were added with stirring. At 60 ° C, 60 g of peracetic acid (40%) were added so that the temperature of the mixture did not exceed 90 ° C, which required about 1 h. The mixture was stirred for an additional 1 h, cooled, diluted with water and extracted with ether or hexane. After drying the extract over sodium sulfate and distilling off the residue, the residue was fractionated in vacuo. The conversion of trans-verbenol was 84% and the selectivity to verbenone was 0.66.

Analysis of the oxidation products was performed by gas chromatography (GLC), using 2,000 mm long, 3 mm diameter glass columns packed with 10% 0V-17 / Chromaton N-AW-DMCS at 110-250 ° C with a 10 ° C gradient. .min ^- · ¹ ·. The temperature of the dispenser was 250 ° C, the FID type detector was 270 ° C and the nitrogen flow was 30 cm ³ . min ^- ^. The internal standard was dipropyl phthalate (m.p. 305 ° C).

Physical constants of compounds

compound molecular weight ’ m.p. t. IN . _d 20 ^d 4 kg.m ' ³ „20 ⁿ D alpha-pinene 136.2 - 156 874 1.4660 verbone 150.2 - 253 973 1.4961 cis-verbenol 152.2 70 215 - - trans-verbenol 152.2 14 250 965 1.4914

CS 271986 Bl

Claims (5)

OBJECT OF THE INVENTION A process for the preparation of verbenone from alpha-pinene by oxidation with oxygen in the presence of a catalyst and an initiator at a temperature of 50 to 80 ° C for 4 to 12 hours, characterized in that the reaction is carried out in the presence of 0.005 to 0.1 mol of a copper complex of Cu molar composition: Br: pyridine = 1: 2: 2 of the dipyridyl-mela dibromide type as catalyst per 1 kg of alpha-pinene feed, is initiated with azobisisobutyronitrile or organic peroxide compounds and the product is separated by distillation. 2. The process according to item 1, characterized in that a copper phthalocyanine or a chromium salt of a fatty acid having a carbon number of 14 to 18 in an amount of 0.001 to 0.006 mol, based on 1 kg of alpha-pinene charge, is used as cocatalyst. 3. The preparation method according to item 2, characterized in that the reaction is carried out. in the presence of a catalyst solvent which is carboxylic acids or their esters. 4. The process according to item 3, characterized in that before distillation, the mixture is heated to 90 DEG C. for 0.5 to 1 h with the addition of 1 to 3% by weight of boric acid, based on the weight of the mixture. 5. The process according to items 1 to 4, characterized in that the distillation product is subjected to reoxidation with peracetic acid or a mixture of hydrogen peroxide and acetic acid in the presence of cobalt salts of carboxylic acids as catalysts at a temperature of 60 to 90 ° C.