CH642649A5 - PROCESS FOR THE PREPARATION OF A TERPENIC ETHER. - Google Patents

Description

The present invention relates to the field of perfumery, more precisely it relates to a process for the preparation of a terpene ether, 2- [2-methylprop-1-en-1-yl] -4-methyltetrahydro-pyran.

This ether, of formula:

better known under the name of rose oxide, is a highly appreciated compound in the perfume industry.

Since its discovery in 1960 [see Swiss patent N ° 395406], numerous scientific publications have reported on new syntheses for the preparation of rose oxide. It has also appeared in use that the cyclanic isomer eis was of major interest, hence the need to develop manufacturing processes which can make it possible to obtain said isomer, or even a mixture containing predominant proportions of that -this.

Most of the known methods provide for the use of acyclic intermediates or the introduction of the 2-isobutenyl substituent on the pyrannic ring previously formed. A new synthetic approach, starting from 3-methylbut-2-ene-1-al and 2-methyl-but-1-ene-4-ol, was formulated by J.P.H. Tyman and BJ. Willis [see “Tetrahedron Letters”, 51, 4507 (1970)], said method can be illustrated as follows:

0

H

According to the authors cited above, the reduction of the methylene intermediate, or rose dehydroxide, is carried out by hydrogenation in a homogeneous phase in the presence of tin chloride11 and hexachloroplatinic acid. It was thus possible to obtain a mixture consisting of approximately 91% of the eis isomer and 9% of the trans isomer. Unfortunately, such a method encounters, in its industrial application, a major economic difficulty: the price of the hydrogenation catalyst is indeed very high.

US Patent No. 3163658 (granted December 29, 1964) describes a process for the preparation of mixtures of rose oxide with some of its isomers, which process is characterized by the high temperature heat treatment of 3,7-dimethyloctane- 1,6,7-triol with a catalyst for dehydration and acid cyclization. As a catalyst, it has been suggested to use phosphoric acid, p-toluenesulfonic acid, sulfuric acid (40-70%), alkali metal bisulfates, boron oxides and copper chlorides . Although the content of rose cisoxide in the mixtures thus obtained was higher than in the mixtures used as starting materials, the conversion rates of the trans isomer into eis, under the stated reaction conditions, were very low.

The present invention provides a new and advantageous solution to the problem posed.

It has in fact been discovered that it is now possible, thanks to the process as defined by claim 1, to obtain mixtures of rose oxide containing predominant amounts of its isomer isis.

The present invention further relates to a process for the preparation of mixtures of rose oxide containing preponderant amounts of its isomer eis, said process being characterized in that a methylene cyclic ether of formula is subjected to hydrogenation:

in the presence of a catalyst consisting of Raney nickel or palladium to provide a mixture of eis- and trans-2- [2-methyl-prop-1-ene-1-yl] -4-methyltetrahydropyran, and that l 'said mixture is then enriched in the eis isomer by treatment with an acid agent.

It has been found that, by the process defined by claims 1 to 8, isomeric mixtures are obtained whose rose cisoxide content exceeds 80-85% by total weight of the mixture obtained. Though

5

I "

15

20

25

30

35

40

45

50

55

60

65

3

642,649

the concentration of the desired isomer does not reach the value indicated for the product obtained by Tyman and Willis, the process of the invention proves to be more profitable, from the point of view of its industrial application, than that described by these authors , the price of the hydrogenation catalyst as well as the acid reagent being much lower than that of the SnCl2-H2PtCl6 mixture. In addition, it has resulted from this that the particular isomeric mixtures obtained using the process of the invention constitute raw materials of excellent olfactory quality, any additional purification being therefore superfluous for most practical uses. io

According to a special embodiment of the process of the invention, as defined by claim 1, a protic acid, such as for example sulfuric or phosphoric acid, an acid diatomaceous earth or a Lewis acid. BF3, in particular in its form of boron trifluoride etherate salt, is preferably used. Such a treatment is carried out in an atmosphere of inert gas, of nitrogen or of argon for example, at ambient temperature or at a temperature higher than this, and in the presence of an inert solvent, such as an aromatic hydrocarbon such as benzene or toluene, or an ether. 20

According to the invention as described in claim 8, Raney nickel is preferably used as hydrogenation catalyst. It has in fact been observed that such a catalyst allows the almost exclusive reduction of the cyclic methyl ether to a cis / trans (4/6) isomeric mixture of rose oxide, this product being accompanied by small amounts. , of the order of 3 to 5%, of nerol oxide. When the catalytic hydrogenation is carried out in the presence of a palladium catalyst, such as palladium on carbon, at 5 or 10%, or partially inactivated palladium according to Lindlar [see for example “Helv. Chim. Acta ”, 35, 446 30 (1952)], the mixture of rose oxide obtained, on the other hand, is accompanied by much larger amounts of nerol oxide, these amounts being able to go up to 20 or 30%. On the other hand, the isomeric ratio eis: trans of the mixture of rose oxide thus obtained appears more favorable; in these cases it contains approximately 65% of the 35 eis isomer.

The above-mentioned catalytic hydrogenation is carried out according to the usual conditions, at ambient temperature or at a temperature slightly lower than this, and at ordinary pressure. Preferably, said hydrogenation is carried out by dissolving the rose dehydrooxide (I) in an inert solvent, such as an alcohol such as methanol or ethanol.

The rose oxide present in the mixture obtained, accompanied by nerol oxide, can be separated from the latter by simple distillation, optionally using a Vigreux type column. 45

The next step is carried out by treating, with an acid agent, the isomeric mixture of rose oxide obtained, in accordance with the conditions indicated above.

Rose dehydrooxide (I), used as a starting material in the above process, can be prepared in accordance with 50

process described in the aforementioned literature [see “Tetrahedron Letters”, 51, 4507 (1970)]. 3-methylbut-2-ene-1-al and 2-methyl-but-1-ene-4-ol, used in the preparation of rose dehydrooxide, are commercial products.

The invention is illustrated in more detail by the following examples in which the temperatures are indicated in degrees centigrade and the abbreviations have the usual meaning in the art.

Example 1:

at. S g (0.033 mol) of pink dehydrooxide in 25 ml of ethanol were hydrogenated at 15 ° in the presence of 0.250 g of Raney nickel previously washed with water and ethanol. After 3 h, the absorption of hydrogen was 755 ml. The reaction mixture was filtered and the clear filtrate evaporated to provide a residue which, by distillation using a Vigreux column, gave a fraction having Eb. 65-70 ° / 8 Torr. This consisted of 4.5 g of a mixture of eis- and rose transoxide in a respective weight ratio of 4: 6.

b. 45 g of an isomeric mixture of rose oxide, obtained according to the process indicated above under letter a, in 200 ml of toluene, were mixed at 25 ° with 5 ml of boron trifluoride etherate. The operation is carried out under a nitrogen atmosphere. 3 hours were enough to reach the desired balance. The mixture was then poured onto ice to which an NaHCO 3 solution was added, then, once separated, the organic phase was washed until neutral, dried and concentrated. By fractional distillation of the residue obtained, 39 g of an Eb fraction were obtained. 65-70 ° / 8 Torr. This fraction consisted of an isomeric mixture of eis and rose transoxide, the content of the eis isomer of 85% (yield = 86.5%).

By replacing Raney nickel in the above process with palladium on carbon, or a catalyst of the so-called Lindlar type, a similar course of the reaction was observed. However, the hydrogenation mixture obtained contained amounts of up to 30% of nerol oxide. The mixture of rose oxide isolated by means of fractional distillation of the mixture obtained consisted of approximately 65% of isis isomer.

Example 2:

45 g of rose transoxide, obtained from the 4: 6 mixture of eis- and rose transoxide as prepared in Example 1, under letter a, by fractional distillation using a column with a rotating band : Eb. 68-69 ° / 8 Torr; n24 ° = 1.4591; d24 ° = 0.8770, were treated, according to the method indicated under letter b of Example 1, with boron trifluoride etherate using the quantities and the reaction conditions indicated in said example. An isomeric mixture of eis and rose transoxide was thus obtained, the content of the eis isomer of which was approximately 85%.

The table summarizes other tests carried out in a similar manner to that described in paragraph b of Example 1.

Solvent

Catalyst (%) '

Reaction time (h)

Reaction temperature (° C)

Isometric report cis / trans

Toluene

12.5

bf3

3 '/ 2

25

80/20

Toluene

5

bf3

4

25

89/11

Toluene

5

bf3

1%

35

89/11

Toluene

5

TsOH

28

30

83/17

Petroleum ether

(30750 °)

5

bf3

3

30

88/12

Methanol

5

bf3

32

30

83/17

1% by weight relative to the weight of the rose oxide used.

2 Reaction product.

Board

R

Claims (8)

642,649 CLAIMS 1. Process for the preparation of an isomeric mixture of trans-2- [2-methylprop-1-en-1-yl] -4-methyltetrahydropyran eiset having a content of cyclic isomer eis greater than or equal to 80% weight, characterized in that the trans-2- [2-methyl-prop-1-en-1-yl] -4-methyltetrahydropyran, or any cis-trans mixture whose content in said trans isomer is greater or is subjected, equal to 20% by weight, to treatment with an acid agent. 2. Method according to claim 1, characterized in that the acid agent is a mineral protic acid. 3. Method according to claim 2, characterized in that the mineral protic acid is phosphoric acid. 4. Method according to claim 1, characterized in that the acid agent is selected from Lewis acids. 5. Method according to claim 4, characterized in that the Lewis acid is BF3. 6. Method according to claim 5, characterized in that the BF3 is in the form of boron trifluoride etherate. 7. Method according to claims 4 to 6, characterized in that the acid treatment is carried out in the presence of an inert organic solvent, such as an aromatic hydrocarbon. 8. Process for the preparation of an isomeric mixture of 2- [2-methylprop-1-en-1-yl] -4-methyltetrahydropyran, consisting mainly of the cyclanic isomer eis, by hydrogenation of a cyclic ether methylene of formula: characterized in that said hydrogenation is carried out in the presence of a catalyst consisting of Raney nickel or palladium to provide a mixture of eis- and trans-2- [2-methylprop-1-en-1-yl] - 4-methyltetrahydropyran, and enriches said mixture with the eis isomer by treatment with an acid agent.