CS215485B1

CS215485B1 - Method for preparing verbenone

Info

Publication number: CS215485B1
Application number: CS99681A
Authority: CS
Inventors: Ladislav Kalvoda
Original assignee: Ladislav Kalvoda
Priority date: 1981-02-11
Filing date: 1981-02-11
Publication date: 1982-08-27

Abstract

Vynález se týká způsobu přípravy verbenonu oxidací α-pinenu kyslíkem v přítomnosti organické báze a katalytického množství solí kobaltu, načež se získaná směs kyslíkatých monoterpenů oxiduje v kyselém prostředí kysličníkem chromovým. Získaný surový verbenon se přímo může použít pro přípravu cis-verbenolu, jedné složky agregačního feromonu lýkožrouta smrkového (Ips typographus)The invention relates to a method for preparing verbenone by oxidizing α-pinene with oxygen in the presence of an organic base and a catalytic amount of cobalt salts, after which the obtained mixture of oxygenated monoterpenes is oxidized in an acidic environment with chromium trioxide. The obtained crude verbenone can be directly used for the preparation of cis-verbenol, one component of the aggregation pheromone of the spruce bark beetle (Ips typographus)

Description

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BACKGROUND OF THE INVENTION The present invention relates to a process for the preparation of verbenone oxidations of α-piperene by oxygen in the presence of cobalt salts.

Verbetone, 4,6,6-trimethylbicyclo [3.1.1] hept-3-en-2-one, forming part of some essential oils, is used in perfumes and as an intermediate for the preparation of aromatic terpene compounds. It has recently been found that optically active (S) -cis-verbenol and (R) -cis-verbenol are one of the components of the bark beetle family. In addition, it affects the behavior of some species of bark beetles (Dendroctonus). (JP Vité: Biology in unsererZeit 8, 112 (1978) and references cited therein). Because optically active cis-verbols are readily prepared from the corresponding verbenones by reduction with lithium aluminum hydride, a greater demand is produced after the verbenone.

The optically active verbenone is prepared in high yield from the appropriate optically active α-pineone by the procedure of K. Sea: Agr. Biol. Chem. 40, 415 (1976). However, this process has the disadvantage of requiring work with toxic and costly lead dioxide and problems with the treatment of waste products. A number of methods of oxidation by air or oxygen, both catalysed and non-catalysed (Gildemeister and Hoffmann: Die Aetherischen Oele, Vol. IIIc, Akademie Verlag, Berlin 1963, p. 345). According to one of these, the autooxidation of α-pinene to produce the phenol, verbenone and polymers is carried out in the presence of cobalt, lead or manganese oleate at a temperature above 40 ° C. (K. Suzuki, Bull. Inst. Phys. Chem. Res. (Tokyo) 14, 179 (1935), Chem. Abstr. 29.5830).

The reproduction of some known oxygen including oxidation processes in the presence of cobalt salts in an neutral or acidic environment afforded poor yields of relatively complicated reaction mixtures economically viable. When using catalysis with cobalt salts in the alkaline medium of strong inorganic bases, the reaction proceeded poorly. However, carrying out the oxidation with oxygen under the catalysis of solemicobalt in an organic base environment, a reaction mixture was obtained which could be further converted to verbenone in a simple manner. SUMMARY OF THE INVENTION The present invention relates to a process for the preparation of verbornone, characterized in that the α-pinene is oxidized in the presence of an organic base and a catalytic amount of cobalt salts, preferably cobalt salts of 10 to 20 carbon fatty acids. ° C for 10 to 48 hours, the reaction mixture obtained is distilled into portions formed by unreacted α-pinene, oxygen monimonoterpenes and polymers, whereupon the α-piperene fraction is used for re-oxidation with oxygen and oxidized with oxygenated monoterpenes in the acid medium by chromium oxide. For the oxidation of α-piperene in the presence of an organic base of cobalt ions, the temperature of the reaction mixture is of considerable importance. The reaction proceeds at room temperature, but is slow and requires unacceptably long periods of time. 215485

By increasing the temperature, the reaction is accelerated, but the formation of polymers increases. At temperatures above 80 ° C, the formation of polymers is so high that oxygen consumption stops. The optimum relationship between the reaction intermediate and the polymer formation is in the range of 50 to 60 ° C. The oxidation is conveniently carried out under vigorous stirring in an atmosphere of air, preferably oxygen.

The oxidation reaction intermediate is a verbenyl peroxide which, in the presence of an organic base and an ion cobalt, provides a reaction mixture consisting essentially of unreacted α-pinene, from the compounds of Scheme I and polymers.

The reaction mixture is separated by distillation into unreacted α-pinene and oxygen monoterpenes. Unreacted α-pinene can be used directly for re-oxidation, the mixture of oxygen derivatives can easily be converted to verbenone. The reaction is carried out by oxidation of the oxygenated monoterpene acid fraction with hexavalent chromium salts. Preferably, the sulfuric acid in chromium trioxide is used at a reaction temperature of 0-10 ° C in a conventional reaction product to obtain a purity of verbenone which is completely sufficient for example. for subsequent reduction to cis-verbenol. Pure verbenone can be prepared from the crude product by distillation on a several-column column and / or silica gel column chromatography.

Cobalt cobalt salts of 10 to 20 carbon atoms are preferably used as the source of cobalt ions for reasons of solubility, although other salts may be used. The amount of catalyst used ranges from 0.1 to 5% by weight. % of the mixture, preferably 1 wt.

As organic bases, tertiary organic bases such as triethylamine, pyridine or quinoline can be used. Pyridine is preferably used. The amount of organic base depends on its type and ranges from 1 to 20% by weight of the reaction mixture.

The course of both oxygen oxidation and chromium oxide oxidation is followed by chromatography on a silica gel layer and by gas chromatography in a manner known to those skilled in the art.

For the practical use of verbenone as an insect behavioral agent or for the conversion of the corresponding optically active cis- or trans-verbene, it is necessary that the optical activity of the compounds is maintained during the reactions. The process of the invention maintains this condition, as can be seen from the following examples, and can therefore be used for the desired purposes.

The invention is further illustrated by the following examples.

Claims

EXAMPLE 1 2720 g (20 mol) of (-) -. Alpha.-pinene [.alpha.] D = -51.6 DEG, 27 g of cobalt palmitate and 200 ml of pyridine are placed in a reactor equipped with an effective oxygen supply. The reactor contents are heated to 60-65 ° C and oxygen is introduced at a temperature above 200 Pa at this temperature. After 24 hours, the reaction is discontinued, the reaction mixture is allowed to settle, the bottom dark (about 100 ml) is separated, which causes irregularities in the distillation and the upper phase is vacuum distilled. 1300 g) and a fraction from 65 to 130 ° C at 2.6 kPa (1300 g). A fraction boiling up to 65 ° C at 2.6 kPa (1300 g) of the major portion of unreacted α-pinene and pyridine. Tofraction is used without further modification, after the addition of palmitanucobalt, α-pinene, and the adjustment of the pyridine concentration for the new oxidation as described above. An oxidation mixture prepared from 430 g of oxide is added dropwise to the boiling fraction of 65 to 130 ° C at 2.6 kPa (1300 g) dissolved in acetone (2600 ml) with intensive stirring and cooling to 10 ° C (dry ice bath). chromium, 1200 ml sulfuric acid and 2200 g water. After the addition was complete, the reaction mixture was stirred for a further 30 minutes. diluted with 3 liters of water. The separated oil layers were separated and the aqueous phase was extracted with ether (2 x 1000 mL). The oily layer and ether extracts were combined and washed with water and aqueous sodium bicarbonate. After drying over magnesium sulfate, the ether is distilled off and the residue is vacuum distilled. By distillation over a 5-gallon boiling column, the fraction from 103 to 106 ° C at 2.0 kPa is collected. Yield of crude verbenone 655 g [α] D 20 = -208 ° (c = 1.1, chloroform), purity 91% (gas chromatography). The total yield of verbene after reoxidation of unreacted α-pineone is 990 g (33.5%). The crude product can be used directly for the next reaction, for example to reduce to (S) -cis-verbenol. The crude verbenone (5 g) is purified by chromatography on an object

A process for the preparation of verbenone, characterized in that α-pinene is oxidized with oxygen in the presence of an organic base and a catalytic amount of co-salt salts, preferably cobalt salts of 10 to 20 carbon atoms, at a temperature of 40 to 80 ° C. 10 to 48 hours, the reaction mixture obtained is separated by distillation into portions consisting of unreacted α-pinene, oxygen monoterpenes and poly-215485 silica gel column with a mixture of petroleum ether with increasing ether content (1% to 5%). The verbone-containing fractions are combined, the solvent is evaporated and the evaporation is distilled under vacuum. Verbenone [α] θ = -217 ° (c = 1.2, chloroform) is 98.5% by gas chromatography. Example 2 The procedure of Example 1 was repeated except that (+) - α-pinene [α] 4 = + 25.4 was used as the starting material. Yield 35.2% veneer [α] θ = + 176 ° (c = 0.9, chloroform). EXAMPLE 3 100 g of lithium aluminum hydride are suspended in 4 liters of a 6 liter flask equipped with a stirrer, a scrubber and a reflux condenser. 1200 g of crude hoverbone, prepared according to Example 1, was added dropwise to the slurry at such a rate as to maintain the reaction mixture at the boiling point. After the addition was complete, the reaction mixture was stirred for 60 min, then quenched by addition of 265 mL of 30% NaOH and then 130 mL of NaOH. The reaction mixture was allowed to stand overnight, the ether phase was decanted, filtered and the insoluble matter on the filter was washed with ether. The ether solution was concentrated and the residue was crystallized from petroleum ether at -25 ° C. The precipitated crystalline fraction was separated and washed with petroleum ether cooled to - 80 ° C. Yield 710 g of (S) -cis-verbenol 1.1.69 to 71 ° C [α] D = + 8.3 ° (c = 1.0, methanol) and [α] 4 = -13.1 ° (c = 0.5, chloroform). Deviations in the rotation values over the literature (K. Moir et al. Agric. Biol. Chem. 40, 1611 (1976)) are a moderate admixture of trans-verbenol and can be removed by further crystallization. Example 4 Using the procedure of Example 3 using (+) - verbene prepared according to the procedure of Example 2, a (R) -cis verbenone is prepared from 68 to 70 ° C [α] D = -8.9 ° (c = 0, 9, methanol [α] D = + 10.9 ° (c = 1.1, chloroform). BRIEF DESCRIPTION OF THE INVENTION Measurements, whereupon the α-pinene containing moiety is used for re-oxidation with oxygen, and the proportion of oxygenate mono-therapens is oxidized in an acidic medium with chromium oxide.

2. A process according to claim 1 wherein the oxygen is oxidized in the presence of pyridine.