CS258634B1 - Method of verbenone preparation - Google Patents

Abstract

The solution is to eliminate harmful ones effects of toxic catalysts such as demanding disposal of production waste. The essence of the solution is that the reaction is taking place in the presence of 0.005 to 0.1 mole of cobalt complex per 1 kg of alpha-pinene in composition cobalt Co: Br: pyridine complex is 1: 0.1 to 5: 0.1 to 10. Preferred is a cobalt complex of dipyridyl- Cobalt-bromide.

Description

The invention relates to a process for preparing verbenone.

Verbenone 4,6,6-trimethylbicyclo- (3,11-hept-3-en-2-one is prepared by oxidation of alpha-pipene by conventional methods. Oxidation with lead acetate in acetic acid preferably with high yields but with the disadvantage of its toxicity as with the problems of waste treatment - Sea K .: Agr Biol Chem 40, 415-8 (1976), CA 84, 135 842. Oxidation in benzene and alkaline medium and the obtained trans-verbenol after reoxidation with chromium trioxide are possible pyridine was provided by verbenone Mitsubishi Chem. Ind. Co. Ltd .: Japanese Patent 8130, 940 CA 95, 150 956. Oxidation by means of lead oxide, chromium oxide or even manganese dioxide is possible in pyridine, acetone, benzene or even ligroin. known from Iglesias D., Dora IA, Retamar JA: Essenze Deriv. Agrum., 42, 41-7 (1972), CA 77, 164 860. Alpha-pinene oxide products were obtained by oxidation with oxygen at temperatures up to 100 ° C without catalyst. transverbenol and verbenone - Moore RN, Golumbic C., Fischer GS: J. Amer. Chem., Soc., 78, 1173-6 (1956) Similar to air oxidation at 60-90 ° C, verbenol and verbenone were obtained in addition to cosmetic products - Bain JP, Booth AB, Klein EA, (Glidden Co). .): US Pat. No. 2 863 882 (1958), CA 53, 8 194. At temperatures above 50 ° C, a relatively large number of by-products mainly of bituminous products are already formed; at 50 ° C, the desired products are obtained as before, in a better yield - Bain J. Gary WY (Glidden Co.): U.S. Pat. No. 2,911,441 (1959J CA 55, 607). Oxidation with oxygen at 40 ° C in the presence of oleate or cobalt or manganese stearate as catalyst provided verbenone in up to 40% yield - Suzuki K .: Bull. Inst. Phys. Chem. Res. (Tokyoj: 14, 179-81 (1935) CA 29, 5830) Oxidation with oxygen at temperatures of 30 to 40 ° C in the presence of benzaldehyde and cobalt acetate as catalyst gave verbenol and verbenone in yields above 40% - Romanichin AM, Popova NI , Prudničenko EK: Chim Chim Technol 20, 177-9 (1977): Oxidation with oxygen at 60 to 65 ° C in the presence of pyridine and cobalt palmitate as a catalyst yielded verbenone in 33% yield after re-oxidation with chromium oxide - Kalvoda L , Vrkoč J .: Pat. CSSR AO 215 485 (1982) By modifying the procedure using dibenzoyl peroxide as the initiator or peracetic acid initiator, verbenone was obtained in a yield of up to 40%, while the reaction time was also shortened. from 24 to 18 hours - Collective: Pheromones, Research report by VÚCHT Bratislava 1983. Autooxidation with oxygen at 25 ° C in the presence of cobalt naphthalate as a catalyst also yielded a mixture of verbenol and verbenone - Bohe R.L .: Essenze Deriv. Agrum. 53, 148-56 (1983), CA 101, 211481. Oxidation with oxygen or air at 50 ° C for 20 hours in the presence of a dipyridyldiodium copper complex catalyst provided verbenone in good yield - Bhaduri S., Mahandru Μ. M. (Indian Explosives Co., J: Brit. Pat. 2,078,223 (1982), CA 98,218,066.) Oxidation with oxygen in chlorobenzene in the presence of palladium (II) chloride and copper (I) chloride catalysts with additives such as lithium, sodium, potassium and barium, verbenol and verbenone were obtained in up to 57% yield - Sirakova V., Dimitrov D., Angelov V .: Bolg., Akad. Nauk 37, 767-9 (1984), CA 101, 211 484. Oxidation at temperatures of 68-80 ° C, the yield of the products as described in Dimitrov, D., Sirakova, V., Angelov, V., Stefanova, R .: Chim. 56 (1984), CA 101, 38 676. The oxidation of oxygen at 80 [deg.] C. using azodisobutyronitrile (AIBNj as initiator) also produced, in addition to cosmetic products, also verbenone - Pritzkov W., Van Trien V., Schmidt-Renner W. : Míltitzter Berichte 1 982, 17-25. Oxidation with oxygen at 70 to 80 ° C using AIBN In addition to other products, verbenone was also initiated, with the main purpose being kinetic measurements and probability suggestions. mechanism of reaction - Martinez de la Cuesta P.J., Rus Martinez E., Garcia Herruzo F .: Ann. Quim., Ser. A 80, 262-6 (1984).

Oxidation of alpha-pinin with tetravalent lead salts or even trivalent thallium salts is disadvantageous in view of the high toxicity of the reagents and thus the disposal problems. Oxidation in alkaline environment by cobalt or manganese salts. metal soaps proceed well and produce good yields, but the presence of harmful organic bases such as pyridine, quinoline, target. amines etc '. In addition to unpleasant work, they also cause more demanding health protection for workers. Also, treatment of the reaction mixture containing soluble metal soaps is more difficult due to the considerable foaming in vacuum distillation. In some processes, considerable economic demands are mainly caused by waste disposal and operation of technological equipment.

These drawbacks are overcome by the preparation of verbenone from alpha-pinene by oxidation with oxygen in the presence of a catalyst at a temperature of 50 to 80 ° C for 4 to 12 hours, which is characterized in that the reaction proceeds in the presence of 0.005 to 0.1 moles of cobalt complex The composition of the cobalt complex Co: Br: pyridine is 1: 0.1 to 5: 0.1 to 10. The reaction proceeds in the presence of a dipyridyl-cobalt-dibromide cobalt complex. The reaction may be carried out in the presence of a catalyst solvent such as carboxylic acids, their anhydrides and / or esters.

The reaction may be carried out in the presence of azonitrile carboxylic acids and / or organic peroxide compounds.

The reaction mixture obtained is separated by distillation into a fraction containing mainly unreacted pinene, which can not be recycled, and into a fraction of oxidation products containing mainly oxygen monoterpenes, from which it is possible to distill the vacuum to obtain verbenone and trans-berbenol in a good purity ratio of 70 to 85%. for further processing.

The oxidation product fraction can be subjected to reoxidation in an acidic environment with a hexavalent chromium salt homogeneously or by a phase transfer method at temperatures of 0 to 10 ° C, respectively. in complexes with organic bases up to 30 ° C. In this process, mainly transberbenol is oxidized to verbenone and this can then be recovered from the mixture by rectification under vacuum in very high purity of 87-97%, which is sufficient for further processing by reduction to the desired cis-verbenol.

The temperature range used is 30 to 90 ° C, preferably about 55-65 ° C. At lower temperatures there are less by-products but the reaction time is too long, at higher temperatures the proportion of by-products mainly of bituminous character is already very high and their formation is practically unbearable above the temperature of 80 ° C. of the reaction mixture. The removal of the reaction water by a suitable device has a favorable effect on the reaction. The reactor must also have a large reserve space for considerable foaming of the oxidized pinene, namely 30 to 50% of the height of the pinene column in the batch. The catalyst used for this process for the preparation of verbenone is of the type dipyridylcobaltdibromide (PZCoBn) and can be prepared in a relatively simple manner in a very pure form, the well sealed being stable and thus effective for at least 6 months. It can also be prepared in a reaction mixture "in situ" from cobalt bromide and cobalt acetate and pyridine or even hydrogen bromide additives.

Example 1

Oxidation of alpha-pinene

A glass cylinder oxidizing reactor (800 mm long, 45 mm diameter) with an electrically heated jacket, a thermometer, a cooling coil, and possibly an azeotropic water take-off, with oxygen supplied from below through a frit, 500 grams of alpha was metered in after rotating the oxygen. -pinene (97% pure GLC). After the reactor was allowed to warm to 60 + 1 ° C, the oxygen flow was adjusted to 20 L. h ¹ and 2.0 g (0.005 mol) of finely atomized dipyridyl-cobalt-dibromide catalyst (PyzCoBrz see note) were added successively at the top of the reactor. The mixture was oxidized for 6 h, allowed to cool to about 30 ° C, filtered and then either passed through a packed column (length).

000 mm, diameter 25 mm, glass or porcelain Raschig rings) heated to 110 to 115 ° C or kept in a conical flask at 30 minutes with agitation to destroy the peroxides present. After cooling, the reaction mixture was distilled under vacuum at about 2.6 (20 torr) for two fractions, namely fraction I to 70 ° C (which contains predominantly unreacted pinene that can be recycled) and fraction II to the mixture temperature. in a 180 ° C flask (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 a 6 TP puncture column. 234 g of unreacted pinene (fraction I) and 143 g (28.6%) of oxidation products (fraction II), from which 47.6 g (33.3%) of verbenone and 8.9 g (6.2%) were obtained %) of verbenol.

The catalyst was prepared as follows: A solution of 8 g (0.1 mol) pyridine in 100 ml butanol heated to 80 ° C was gradually added over a period of about minutes to a solution of 14 g (0.04 mol) cobalt bromide (hexahydrate) in 300 mL of butanol at a temperature of 80 to 90 ^e C. After partial cooling to 50 DEG C., the resulting crystals blue sucked off, washed with ether and dried in a drying cabinet at max. 60'C and good sealed in a stock bottle.

Example 2

As in Example 1, a mixture of the same composition was used, the catalyst was added at a temperature of 90-100 ° C (better solubility quota) and after 10 minutes the temperature was adjusted to 60 ° C. Addition of 0.8 g (0.005 mol) of azo-bis-isobutyronitrile (AIBN) was used as initiator. The reaction mixture obtained was worked up similarly to give 210 g of unreacted pinene (fraction I) and 162 g (32.4%) of oxidation products (fraction II) from which

67.6 g (41.7%) of verbenone and 12.8 g (7.9%) of verbenol.

Example 3

As in Example 1, a mixture of the same composition was used to which 1 ml of 77% cumene hydroperoxide (KHP) was added as an initiator. The reaction mixture obtained was worked up similarly to give 245 g of unreacted pinene (fraction I) and 130 g (26%) of oxidation products (fraction II), from which 42.6 g (32.8%) of verbenone and 4 g of fraction were obtained. .8 g (3.7%) of verbenol.

Example 4

As in Example 1, a mixture of the same composition was used, to which 50 g of glacial acetic acid (as catalyst solvent) and 1 ml of 77% KHP initiator were added, 240 g of pinene (fraction I) and 136 g (27.2 pere) of fraction II, from which 15.5 g (11.4%) of verbenone and 46.8 g (34.4%) of verbenol were obtained.

Example 5

As in Example 1, a 500 g alpha-pinene feed was used. After bringing the reactor to 50 + 1 ° C, 1.64 g (0.005 mol) of cobalt bromide (hexahydrate), 0.8 g (0.01 mol) of pyridine and 50 g of acetic acid were added to the reactor. After about 10 minutes, 1 ml of 77% KHP was added and the reaction was continued as in Example 1 for a reaction time of 10 hours. 193 g of pinene (fraction Ij and 188 g (37.6%) of fraction II) were obtained from which 24.3 g (13.8% of verbenone) and 12.2 g (7.2%) of verbenol were obtained.

example

As in Example 1, a 500 g alpha-pinene feed was used. After bringing the reactor to 70 +1 ° C, 1.15 g (0.005 mol) of cobalt acetate (hexahydrate), 0.8 g (0.01 mol) of pyridine, 1.60 g (0.01 mol) were added to the reactor. 48% HBr and 50 g acetic acid. About 10 minutes, 1 ml of 77% KHP was added and the reaction was continued as in Example 1, with a reaction time of 4 hours. 230 g of pinene (fraction I) and 136 g (27.2 pens) of fraction II were obtained, from which 23.6 g (18.2%) of verbenone and 40.2 g (31.0%) were obtained. verbenol.

Example 7

As in Example 1, a batch of 500 g recycled pinene was used. After the reactor was heated to about 80 ° C, 2.0 g (0.005 mol) of catalyst, 0.8 g (0.005 mol) of AIBN as initiator and 50 g of acetic acid were added. The mixture was heated exothermally up to 100 ° C and after about 10 minutes the temperature of the mixture was adjusted to 60 + 1 ° C and proceeded as in Example 1 for a reaction time of 6 hours. 122 g of pinene (fraction Ij and 176 g (35.2%) of fraction II) were obtained, from which 61.2 g (34.8 pere) of verbenone and 38.2 g (21.7%) of verbenol were obtained.

Example 8

As in Example 1, a 500 g pinene feed was used as a mixture of 250 g pure and 250 g recycled pinene. The catalyst and other additives were added here as in Example 7. After adjusting the temperature to 60 +1 degrees Celsius, the procedure was as in Example 1, the reaction time being 12 hours. 73 g of pinene (fraction I) and 241 g (48.2%) of fraction II were obtained, from which 77.6 g (32.2%) of verbenone and 12.1 g (5.0%) of verbenol were obtained. .

Example 9

As in Example 1, a batch of 400 g recycled pinene was used. After the reactor was heated to 60 ° C, 2.0 g (0.005 mol) of catalyst dissolved in 100 g hot pure alpha-pinene, 0.4 g (0.0025 mol) AIBN as initiator and 50 g acetic acid were added to the reactor. The reactor temperature was adjusted to 60 + 1 ° C and the oxygen flow to 10 L. h ^_1, with the reaction time of 8 hours. 86 g of pinene (fraction I) and 116 g (23.2%) of fraction II were obtained, from which 40.3 g (34.7%) of verbenone and 10.1 g (8.7%) of verbenol were obtained. .

Example 10

As in Example 1, a 500 g pinene feed was used as in Example 8. The catalyst and other additives were added here as in Example 7. After adjusting the temperature to 60 +1 ° C, the reaction was allowed to proceed for 6 hours and then the temperature was raised to 80 +1. ° C and the reaction was allowed to proceed for 2 hours, m.p. j. total 8 hours. 132 g of pinene (fraction I) and 228 g (45.6 pens) of fraction II were obtained, from which 66.4 g (29.1% of verbenone) and 21.7 g (9.5%) were obtained. verbenol.

Example 11

As in Example 1, a feed of 500 g recycled pinene, 1.0 g (0.0025 mol) catalyst and 0.8 g (0.005 mol) AIBN was used, yielding 306 g pinene (fraction I) and 118 g (23 g). 6%) of fraction II, from which 38.6 g (32.7%) of verbenone and 28.7 g (24.3%) of verbenol were obtained.

Example 12

Reoxidation of oxidation products

100 g of Fraction II was weighed into a 1000 ml conical flask with stirrer and thermometer. (32.8%) verbenone and 3.7% verbenol. Hexane (230 mL) and water (180 mL) were added and the reaction mixture was cooled to 0-5 ° C. A chromosulfur mixture (38.5 g CrO ₃ , 142 ml water, 58 g 96% H 2 SO 4) was gradually added thereto so that the temperature of the mixture was max. Low: 14 ° C. Stirring was continued for 1 h, the mixture was partitioned in a separatory funnel, the upper organic layer was separated, and the lower aqueous layer was extracted with 3 X 100 mL hexane. The organic layers were combined, washed with 50 mL of a 10% soda solution and dried with Na 2 SO 4 with 200 mL of water. After the desiccant was filtered off, hexane and hexane were distilled off

1B the bottoms residue was fractionated under 20 torr in vacuo using a small column. The fraction up to 105 ° C is still a pinene that can be recycled here. 70 g of crude product (35.4% verbenone and 0.4% verbenol) were obtained, therefrom 24.8 g of verbenone and 0.3 g of verbenol, representing a yield of 68.8% verbenone and a conversion of 89% verbenol.

Example 13

As in Example 12, 100 g of Fraction II was weighed. (33.3% verbenone and 6.2% verbenol). 100 ml of dichloromethane, 60 ml of water and 1-2 g of cetyltrimethylammonium bromide were added. A chromosulfur mixture (56 g of K 2 Cr 2 O 7, 200 ml of water) was added to the reaction mixture. 75 g [40 ml] of 96% H 2 SO 4) After completion of the reaction, the reaction mixture was treated as the physical constants of the compounds of Example 12 using hexane or dichloromethane for extraction to give 70 g of crude product (36.7%). verbenone and 0.5% verbenol) and therefrom 25.7 g verbenone and 0.4 g verbenol, which represents a yield of 66% verbenone and a conversion of 92% verbenol.

The verbenone thus prepared can be used practically without further treatment for reduction to produce the desired cis-verbenol.

Analysis of the oxidation products was performed by gas chromatography (GLC) using 2,000 mm glass columns, 3 mm diameter with 10% OV-17 packing (Chromaton N-AW-DMCS at temperatures of 110 to 250 ° C with a gradient of 10 ° C min. ^-1. The temperature of the dispenser was 250 ° C, detector FID was 270 ° C and a nitrogen flow rate of 30 cm ^3rd min. ^- '. The internal standard was dipropyl (telephone 305 ° C.

compound molecular mass t. t. ° C t. in. ° C gives ²⁰ kg. m ^-3 Ud ²⁰ (- β-alpha-pinene 136.2 - 156 874 1.4660 verbenone 150.2 - 253 973 1,4961 cis Verbena 152.2 70 215 - - trans Verbena 152.2 14 250 965 1.4914

Verbenone 4,6,6-trimethylbicyclo- (3,1,1) -hept-3-en-2-one is a constituent of some essential oils and is used as a perfume component as well as an intermediate for the preparation of various other aromatic terpenic compounds. Recently, it has been found that optically active (Sj-cis-verbenol and (Rj-cis-verbenol) are important compounds useful as components of pheromone pheromones and also affect the behavior of some species of harmful insects. These compounds are prepared by reducing verbenone becomes an important intermediate for their production.

Claims (4)

258634 1B flask in the flask was fractionated under a pressure of 2.66 kPa (20 torr) using a small column. A fraction up to 105 ° C is a pinene that can be recycled here. 70 g of crude product (35.4% verbenone and 0.4% verbenol) were obtained and 24.8grams of verbenone and 0.3 g of verbenol were present. yield 68.8% verbenone and convert 89% verbenol. Example 13 As in Example 12, 100 g of fraction II was weighed. (33.3% verbenone and 6.2% verbenol). 100 ml of dichloromethane, 60 ml of water and 1-2 g of cetyltrimethylammonium bromide were added. Similar to Example 12, chromosulphurate (56 g K 2 Cl 2 Cl 2, 200 mL of water, 75 g (40 mL) of 96% H 2 SO 4) was added to the reaction mixture, and after completion of the reaction, the reaction mixture was worked up as the physical constants of Compounds 12, with hexane or dichloromethane being used for extraction, 70 g of crude product (36.7% verbenone and 0.5% verbenol) were obtained and 25.7 g of ver-benone and 0.4 g of verbenol, respectively, representing the yield The verbenone prepared in this way is virtually without further modification to be used for the reduction of the desired cis-verbenol.The analysis of the oxidation products was made by gas chromatography (GLC) method using glass columns of 2,000 mm in length, 3 mm in diameter. with 10% OV-17 (Chromaton N-AW-DMCS at 10 ° C to 250 ° C with a 10 ° C, min-1 gradient. The dispenser heat was 250 ° C, the FID was 270 ° C and the nitrogen flow was 30 ° C) cm3 .. min- ' standard was the dispersion numbers dipropylene pylftalát (b. p. 305 ° C). Molecular weight compound m. p. C i. v. C DA20 kg. m-3 UD20 (-) - alpha-pinene 136,2 - 156 874 1,4660 verbenone 150,2 - 253 973 1,4961 cis-verbenol 152,2 70 215 - - trans-verbenol 152,2 14 250 965 1 , 4914 Verbenone 4,6,6-trimethylbicyclo- (3,1,1) -hept-3-en-2-one, constitutes a component of some of the licin and is used both as a perfume ingredient and as an intermediate for the preparation of various other aromatic terpene compounds . Recently, it has been found that the optically active (S) -cis-benzene and (R) -cis-verbenol are important compounds useful as constituents of the pheromone for the cores, and in addition to affecting some species of insects, these compounds are prepared by -ducing the verbenone, which thus becomes an important intermediate for their production. OBJECT A process for the preparation of verbenone from alpha-pinene by oxidation with oxygen in the presence of a catalyst at 50 to 80 ° C for 4 to 12 hours, characterized in that the reaction occurs in the presence of 0.005 to 0.1 mole of cobalt complex per kg of alpha -Pinenation of the cobalt complex Co: Br:: pyridine is 1: 0.1 to 5: 0.1 to 10. 2. Process according to claim 1, characterized in that the reaction is carried out in the presence of a dipyridyl-cobalt-dibromide-type complex. 3. Process according to claim 2, wherein the reaction is carried out in the presence of a catalyst solvent such as carboxylic acids, their anhydrides and / or esters. 4. The process of claims 1 to 3, wherein the reaction is initiated with azonitrile-micarboxylic acids and / or with organic piperidine compounds.