CH628868A5 - Process for the preparation of acyclic monoterpene alcohols - Google Patents

Description

The aim of the present invention is to provide a process for the preparation of the acyclic monoterpene alcohols linalool, geraniol and nerol, which are used as perfume components and can also serve as starting material for the synthesis of fragrances, pharmaceuticals and other 5 useful compounds, which is also of isoprene runs out, requires fewer stages and delivers a higher yield.

The process according to the invention for the synthesis of acyclic monoterpene alcohols is characterized in that isoprene is reacted with a dialkylamine in the presence of a lithium catalyst to give N, N-dialkylnerylamine, which converts nerylamine with the peroxide compound into the N, N-dialkylnerylamine N-oxide , the latter heated for the purpose of thermal rearrangement in the 0-monoterpenyl-N, N-dialkyl-hydroxylamine and this reduced to alcohol. In this process, the desired products are obtained after a few reaction steps and in high yield. The procedure is represented by the following scheme:

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f Et NH

Lithium isoprene catalyst

NEt,

N, N-diethylnerylamine 0

N, N-diethylnerylamine-N-oxide thermal rearrangement

ONEt,

ONEt,

0-Linalyl-N, N-diethyl-0-neryl-N, N-diethyl-O-geranyl-N, N-di-hydroxylamine hydro ^ xylamine ethylhydroxylamine

[

H 1

acyclic monoterpene alcohol I

OH

Linalool

The process according to the invention consists of the following three stages, namely a first stage in which isoprene is reacted with a dialkylamine in the presence of a lithium catalyst to give N, N-dialkylnerylamine, a second stage in which the nerylamine is reacted with a peroxide and then by thermal rearrangement is converted into the OM onoterpenyl-N, N-dialkylhydroxylamine, and a third stage in which the alcohol is formed by cleavage of the ON bond of the hydroxylamine by reduction.

OH

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A solvent is preferably used in the first reaction stage in the reaction of isoprene with a dialkylamine in the presence of a lithium catalyst to give N, N-dialkylnerylamine. For example, you can use a solvent mixture of benzene and ethyl ether. Furthermore, simple solvents such as benzene, tetrahydrofuran, petroleum ether or tertiary amines can be used and in general all solvents which dissolve the starting materials of the first stage and do not prevent the intended reaction.

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Organic lithium compounds such as vinyllithium, phenyllithium, n-butyllithium or metallic lithium can be used as the lithium catalyst. The amount of catalyst is generally less than 1 mol and preferably less than 0.5 mol, based on the dialkylamine compound.

To react isoprene with the N, N-dialkylamine in the presence of solvent and catalyst, the molar ratio of isoprene to N, N-dialkylamine should be more than 2 and the reaction temperature should preferably be in the range from 20 to 80 ° C. Dialkylamines which can be used are dimethylamine, diethylamine, di-n-propylamine and di-n-butylamine and also secondary cyclic amines such as piperidine.

The order in which the components are added to the reaction mixture is not particularly critical, apart from the fact that direct mixing of isoprene with the lithium catalyst should be avoided. For example, the solvent, a secondary amine and the lithium catalyst can be mixed together in this order and then the isoprene added.

In the second stage, the N, N-dialkylnerylamine formed in the above manner is converted into the N, N-di-alkylnerylamine-N-oxide in almost quantitative yield by reaction with a peroxide.

Peroxides suitable for the preparation of this amine oxide are, for example, hydrogen peroxide, cumene hydroperoxide, t-butyl hydroperoxide and peracetic acid. The usual molar ratios are more than equimolar to 5 moles per mole of amine compound. The reaction temperature is advantageously kept below 30 ° C. during the admixing of the oxidizing agents and, after the admixing, is increased to 40 to 90 and preferably 60 to 70 ° C. In the oxidation reaction, solvents such as methanol, propanol, butanol and the like can be used. can be used, but you can also work without solvents.

If excess peroxide remains in the reaction system after the formation of the neurylamine oxide, the following thermal rearrangement is preferably carried out only after the peroxide has decomposed, for example with platinum oxide.

The nerylamine N-oxide is then converted into the 0- (acyclic monoterpenyl) -N, N-di-alkyl-hydroxylamine by thermal rearrangement. The thermal rearrangement proceeds differently depending on the temperature. At temperatures below 110 ° C (or above 110 ° C in a very short time), the 0-linalyl-N, N-di-alkylhydroxylamine is easily obtained. However, if it is heated to a temperature above 110 ° C and below 200 ° C for a sufficient period of time, rearrangement takes place into a 0- (3,7-dimethyl-2,6-octadienyl) -N, N-dialkylhydroxylamine, i.e. 0-geranyl-N, N-dialkyl-hydroxylamine and Ò-neryl-N, N-dialkylhydroxylamine.

To produce linalool, the nerylamine oxide is distilled under reduced pressure, the distillate obtained being the 0-linalyl-N, N-hydroxylamine as a result of the slight rearrangement of the nerylamine oxide into the O-linalyl-hydroxylamine. In the fractional distillation of the hydroxylamine, it is advisable to keep the heating temperature below 110 ° C by lowering the pressure or the like.

For the preparation of 0- (3,7-dimethyl-2,6-octadienyl) -N, N-dialkylhydroxylamine, i.e. 0-Geranyl-N, N-dialkyl-hydroxylamine and Ò-neryl-N, N-dialkylhydroxylamine, the thermal rearrangement is carried out at 110 to 200 ° C. If you heat to less than 110 ° C or too short to more than 110 ° C, the 0-linalyl-N, N-dialkylhydroxylamine is formed. By continuing heating, geranyl or

Nerylhydroxylamine while the linalylhydroxylamine disappears.

To produce geranyl- and neryl-like O- (3,7-dimethyl-2,6-octadienyl) -N, N-dialkylhydroxylamine by heating the nerylamine oxide, the nerylamine oxide is heated to the above-mentioned temperature for a sufficient time so that by thermal rearrangement the geranyl and nerylhydroxylamines are formed, which are then distilled off for isolation.

The O-N bond of the hydroxylamine compounds is then reductively cleaved, giving the alcohol 3,7-dimethyl-2,6-octadien-l-ol. It is preferred to reduce with a metal dust, such as zinc, iron or tin, and an organic or inorganic acid, but other reducing mixtures can also be used, as can other reducing methods.

The distillation of the acyclic mono-terpene alcohol thus obtained gives, as can be seen from the following examples, very pure linalool or a mixture of geraniol and nerol. For example, 90% purity was achieved. The invention thus provides a technically very useful method.

Example 1 Preparation of Linalool

A glass pressure vessel is filled with dry nitrogen and then charged with 17 g of isoprene, 3.7 g of diethylamine, 0.6 g of n-butyllithium and 10 ml of a solvent mixture of benzene and ethyl ether. The reaction is carried out at 50 ° C for 24 hours. The distillation of the reaction product gives the N, N-diethylnerylamine (bp 80 to 81 ° C / 0.5 mm Hg) in 75% yield, based on the diethylamine.

6.2 g of N, N-diethylnerylamine are then reacted with 16 ml of a 30% strength aqueous hydrogen peroxide solution in the presence of 20 ml of methanol in a glass vessel equipped with a distillation column (the hydrogen peroxide solution is added dropwise over the course of 30 minutes while the Reaction mixture is cooled with ice, then the reaction is continued at room temperature for a further 15 hours). After the decomposition of excess hydrogen peroxide, the product is distilled in vacuo, the latter compound being obtained with thermal rearrangement of the N, N-diethylnerylamine-N-oxide to give 0-linalyl-N, N-diethyl-hydroxylamine (bp. 89 to 90 ° C / 2.0mmHg).

3 g of the 0-linalyl-N, N-diethylhydroxylamine thus obtained, 4.5 g of zinc dust and 30 ml of acetic acid are reacted at 35 ° C. for 20 hours, then the reaction mixture is worked up in a conventional manner. Linalool (bp 80 to 82 ° C / 8 mm Hg) is obtained in the distillation in 93% yield (based on N, N-diethylnerylamine).

Gas chromatographic analysis of the linalool thus obtained showed 98% purity. The identification of N, N-diethylnerylamine, 0-linalyl-N, N-diethylhydroxylamine and linalool was carried out by infrared spectroscopy, NMR spectroscopy and mass spectroscopy.

Example 2 Preparation of Linalool

In a reaction vessel of the type described in Example 1, 17 g of isoprene, 3.65 g of diethylamine and 0.2 g of lithium metal in 15 ml of benzene are reacted at 50 ° C. for 12 hours. Distillation of the reaction mixture gives N, N-diethylnerylamine in 14% yield.

This is used to carry out the further steps described in Example 1, by which linalool is obtained in 94% yield, based on the N, N-diethylnerylamine.

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Example 3 Preparation of Linalool The reaction vessel described in Example 1 is charged with 15 ml of benzene, 3.65 g of diethylamine and 0.33 g of n-butyllithium. Then 17.0 g of isoprene are added and the reaction takes place at 65 ° C. for 8 hours. When the reaction has ended, the product is worked up as in Example 1, giving 8.5 g of N, N-diethylnerylamine. The yield was 80.7% (based on diethylamine).

8.5 g of the nerylamine thus obtained and 27 g of methanol are introduced into a glass pressure vessel. The vessel is cooled to 0 to 5 ° C., then 19 g of 35% strength aqueous hydrogen peroxide solution are added dropwise over the course of 30 minutes. The reaction is then carried out with stirring at 20 to 30 ° C for 10 hours. After the reaction has ended, a little platinum oxide is added with stirring and the mixture is left to stand overnight (in order to decompose excess hydrogen peroxide).

The reaction mixture is then filtered and concentrated under reduced pressure. An investigation showed that the N, N-diethylnerylamine-N-oxide was present in the reaction vessel in almost quantitative yield (9.15 g of oxide).

This N, N-diethylnerylamine-N-oxide concentrate was heated at 75 to 80 ° C at a pressure of 20 mm Hg for 1 hour to remove components of lower boiling point. The temperature of the reaction vessel was then raised to 80 to 95 ° C., 10.2 g of distillate having a bp of 85 ° C./1.8 mm Hg to 81 ° C./1.2 mm Hg being obtained (90% yield, based on Nerylamine).

This fraction contained more than 95% 0-linalyl-N, N-diethylhydroxylamine. The 0-linalyl-N, N-diethylhydroxylamine was reduced with zinc and acetic acid using the procedure of Example 1. When the product was distilled, 6.27 g of linalool were obtained.

Example 4 Preparation of Geraniol and Nerol A glass pressure vessel was filled with dry nitrogen and then charged with 17 g of isoprene, 3.65 g of diethylamine and 0.6 g of n-butyllithium and a solvent mixture of benzene and ethyl ether. The reaction took place at 50 ° C. for 24 hours. After the reaction had ended, the N, N-diethyl-nerylamine (bp. 80 to 81 ° C./0.5 mm Hg) was obtained in 80% yield (based on diethylamine).

6.2 g of N, N-diethylnerylamine were then reacted with 16 ml of a 30% strength aqueous hydrogen peroxide solution in 20 ml of methanol to give the N, N-diethylnerylamine oxide. 20 g of N, N-diethylnerylamine oxide and 15 ml of bezol are melted into a glass tube and this is heated at 115 to 125 ° C. for 6 hours. The reaction product is distilled, giving 0- (3,7-dimethyl-2,6-octadienyl) -N, N-di-ethylhydroxylamine in 15% yield (bp. 95 to 97 ° C / 2.0 mm Hg ).

3 g of this compound are reduced with 4.5 g of zinc dust in 30 ml of acetic acid for 15 hours at 27 ° C. The reaction product is worked up in a conventional manner and then distilled, giving the 3,7-dimethyl-2,6-octadien-l-ol (bp. 91 to 93 ° C / 3 mm Hg) in 94% yield.

Gas chromatographic analysis showed a geraniol to nerol ratio of about 2: 1.

Example 5 Preparation of Geraniol and Nerol 17 g of isoprene, 3.65 g of diethylamine and 0.2 g of metallic lithium are introduced into a reaction vessel according to Example 1 with 15 ml of benzene, and the reaction is then continued

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Executed for 12 hours at 50 ° C. The distillation of the reaction product gives the N, N-diethylnerylamine in 14% yield. Using the procedure of Example 4, 3,7-dimethyl-2,6-octadien-l-ol is produced therefrom in 75% yield (based on N, N-diethylnerylamine).

Example 6 Preparation of Linalool A glass pressure vessel is filled with dry nitrogen and charged with 17 g of isoprene, 2.4 g of dimethylamine in 10 g of a solvent mixture of benzene and ethyl ether and 0.4 g of n-butyllithium. The reaction is carried out at 50 ° C. for 24 hours. The distillation of the reaction product gives the N, N-dimethylnerylamine (bp. 55 ° C / 0.5 mm Hg) in 78% yield, based on the dimethylamine.

6.0 g of N, N-dimethylnerylamine are then reacted with 16 ml of a 30% strength aqueous hydrogen peroxide solution in the presence of 20 ml of methanol in a glass vessel equipped with a distillation column (the hydrogen peroxide solution is added dropwise in the course of 30 minutes, while cooling the reaction mixture with ice, then the reaction is continued at room temperature for another 15 hours). After the decomposition of excess hydrogen peroxide, the product is distilled in vacuo (the thermal rearrangement of N, N-dimethylnerylamine-N-oxide to 0-linalyl-N, N-dimethylhydroxylamine taking place due to the heating required for the distillation) receives the 0-linalyl-N, N-dimethyl-hydroxylamine (bp. 65 ° C / 2.0 mm Hg).

A mixture of 3 g of this 0-linalyl-N, N-dimethyl-hydroxylamine, 4.5 g of zinc dust and 30 ml of acetic acid is reacted for 8 hours at 35 ° C., then the reaction mixture is worked up in a conventional manner. When distilling linalool (bp 80 to 82 ° C / 8 mm Hg) is obtained in 94% yield, based on N, N-dimethylnerylamine.

Gas chromatographic analysis of the linalool thus obtained showed more than 99% purity. The identification of 0-linalyl-N, N-dimethylhydroxylamine and linalool as well as N, N-dimethylnerylamine was carried out by infrared spectroscopy, NMR spectroscopy and mass spectroscopy.

Example 7 Preparation of Geraniol and Nerol A glass pressure vessel is filled with dry nitrogen and then charged with 17 g of isoprene, 2.4 g of dimethylamine in a solvent mixture of benzene and ethyl ether and 0.6 g of n-butyllithium. The reaction is carried out at 50 ° C for 24 hours. When the reaction has ended, the N, N-dimethylnerylamine (bp. 80 to 81 ° C./0.5 mm Hg) is obtained by distillation in 80% yield, based on the dimethylamine.

Then 6.0 g of N, N-dimethylnerylamine are reacted with 16 ml of 30% aqueous hydrogen peroxide solution in 20 ml of methanol to give N, N-dimethylnerylamine-N-oxide. 20 g of the amine oxide and 15 ml of benzene are heated in a sealed glass tube at 115 to 125 ° C. for 6 hours. The reaction product is distilled to give the 0- (3,7-dimethyl-2,6-octadienyl) -N, N-dimethylhydroxylamine (bp. 75 ° C / 2.0 mm Hg). Then 3 g of this compound are reduced with 5 g of zinc dust in 30 ml of acetic acid for 8 hours at 35 ° C. The reaction product is worked up in a conventional manner and then distilled, giving the 3,7-dimethyl-2,6-octadienyl-l-ol (bp. 91 to 93 ° C / 3 mm Hg) in 94% yield.

Gas chromatographic analysis of this product showed a geraniol and nerol content in the ratio of about 2: 1.

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Claims (14)

628 868 PATENT CLAIMS 1. A process for the preparation of linalool, characterized in that isoprene is reacted with a dialkylamine in the presence of a lithium catalyst for N, N-dialkyl-nerylamine, the N, N-dialkylnerylamine with a peroxide compound for N, N-dialkylnerylamine-N-oxide implemented, the oxide by thermal rearrangement at a temperature below 110 ° C or very briefly above 110 C in the 0-linal-N, N-dialkylhydroxylamine and reductively cleaves the ON bond of the hydroxylamine compound to form the alcohol. 2. The method according to claim 1, characterized in that one uses a molar ratio of isoprene to dialkylamine of more than 2. 3. The method according to claim 1, characterized in that isoprene is reacted with the dialkylamine at a temperature of 20 to 80 ° C. 4. The method according to claim 1, characterized in that the catalyst used is metallic lithium or an organic lithium compound. 5. The method according to claim 1, characterized in that the lithium catalyst is used in an amount of less than 1 mole per mole of dialkylamine. 6. The method according to claim 4, characterized in that one works with an organic lithium compound in a solvent mixture of benzene and ethyl ether or in tetrahydrofuran, petroleum ether or a tertiary amine. 7. The method according to claim 1, characterized in that isoprene is reacted with diethylamine in the presence of a lithium catalyst for N, N-diethylnerylamine, this is reacted with a peroxide compound for N, N-diethylnerylamine-N-oxide, the oxide by thermal rearrangement converted to 0-linalyl-N, N-diethylhydroxylamine and the ON bond of this hydroxylamine compound reductively cleaves to form linalool. 8. Process for the preparation of 3,7-dimethyl-2,6-octa 10th dien-l-ol, characterized in that isoprene is reacted with a dialkylamine in the presence of a lithium catalyst for N, N-dialkylnerylamine, the N, N-dialkylnerylamine with a peroxide compound for N, N-dialkylnerylamine-N-oxide implemented, the oxide by thermal rearrangement at a temperature above 110 ° C and below 200 ° C in the O-neryl and 0-geranyl-N, N-dialkyl-hydroxylamine and the ON bond of the hydroxylamine compound reductively to form the alcohol splits. 9. The method according to claim 8, characterized in that one uses a molar ratio of isoprene to dialkylamine of more than 2. 10. The method according to claim 8, characterized in that isoprene is reacted with the dialkylamine at a temperature of 20 to 80 ° C. 11. The method according to claim 8, characterized in that the catalyst used is metallic lithium or an organic lithium compound. 12. The method according to claim 8, characterized in that one uses the lithium catalyst in an amount of less than 1 mole per mole of dialkylamine. 13. The method according to claim 11, characterized in that one works with an organic lithium compound in a solvent mixture of benzene and ethyl ether or in tetrahydrofuran, petroleum ether or a tertiary amine. 14. The method according to claim 8, characterized in that isoprene with diethylamine in the presence of a Lithium catalyst to N, N-diethylnerylamine, this with a peroxide compound to N, N-diethylnerylamine-N-oxide, the oxide by heating in 0- (3,7-dimethyl-2,6-octadienyl) - N, N-diethylhydroxylamine umwan-3s delt and the ON bond of this hydroxylamine compound reductively cleaves to form 3,7-dimethyl-2,6-octadien-l-ol. 20th 25th The previously known synthesis of acyclic monoterpene is rather low, since several reaction stages are required and alcohols such as, for example, linalool (formula I) and geraniol require cleaning after each stage. (Formula II) and nerol (Formula III) from isoprene shows the following- 45 The known process proceeds according to the following of the reaction scheme. The yield of this process is schematic: C = Û OH H- OH catalysis t11 "f OH [in] OH M 3rd 628 868