CH680853A5 - New (plus)-(R)-1,4-di:methyl-3-cyclohexene-1-carboxylate - useful perfume ingredient e.g. in soap, shampoo, cosmetics, etc. - Google Patents

Abstract

Methyl 1,4-dimethyl-3-cyclohexene-1- carboxylate in the form of the (+)-(R)-optically active diastereomer of formula (I) or a mixt. contg. a preponderant amt. of (I) is new. (I) is prepd. by subjecting the lactose (+)-(1S-3'R)-tetrahydro -4,4'-dimethyl-2'-oxo-3'- furyl-1,4-dimethyl-3-cyclohexene-1- carboxylate of formula (II) to a transesterification reaction using an alkali metal alkoxide. USE/ADVANTAGE - (I) is a useful perfume constituent with a very fresh, fruity-minty-aniseed fragrance with a hint of pear and an overall aromatic type scent, useful e.g., for perfuming soap, bath and shower gel, shampool, cosmetics, body deodourants, air fresheners, detergents, fabric conditioners, household prods., etc..

Description

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CH 680 853 A5

Description

The present invention relates to the field of perfumery. It relates more particularly to an optically active diastereomer of 1,4-dimethyl-3-cyclohexene-1-methyl carboxylate and to its use as a perfuming ingredient. Methyl 1,4-dimethyl-3-cyclohexene-1-carboxylate can be in two diastereomeric forms of formula

OR

(+) - (R)

(the)

(-) - (S) (Ib)

It is a compound of well-known structure, the utility of which in organic synthesis, in particular for the preparation of ketones and lubricating products, has been the subject of several publications. On the other hand, A. A. Zelenetskaya et al., In Maslo-Zhir. Prom.-St. 1975. 32, mention the usefulness of the esters of formula

R = methyl or butyl for application in perfumes and cosmetics, without however describing the specific odorous properties of the above-mentioned compound. We have indeed been unable to detect in the prior art any mention of these properties. However, this compound is used in several commercial perfume compositions. Furthermore, W. Kreiser et al., In Liebig's Annalen Chem. 1985. 194, describe the structure of the diastereomer of formula (Ib) within the framework of a synthesis of 1,4,4-trimethyIbicyclo [3.2.1] octan-3-one without having noticed any odorous property of this diastereomer.

Now, we have now discovered that the diastereomers of formulas (la) and (Ib) are of certain interest from the perfume point of view and that they have odor properties which are quite distinct from each other, and also of those of the racemic compound, the structure of which is well known.

This is how methyl (-) - (S) -1,4-dimethyl-3-cyclohexene-1-carboxylate has an herbaceous, humus, woody and slightly spicy odor in the resinous-fenugreek direction, also a slightly chemical and moldy, while methyl (+) - (R) -1,4-dimethyl-3-cyclohexene-1-carboxyIate has a very fresh, fruity-mint-anise odor, with a slight pear side, the overall odor effect being of aromatic type. They are therefore quite distinct fragrant notes, both powerful and rising, although to different degrees. Indeed, these two products are also characterized by very different olfactory perception thresholds, the odor of the compound of formula (la) having a perception threshold of 5.85 ppb (parts per billion), while that of the compound ( Ib) is perceptible from a concentration of 20.1 ppb.

As can be seen from the comparison example presented below, it is methyl (+) - (R) -1,4-dimethyl-3-cyclo-hexene-1-carboxyiate which is preferred as fragrance ingredient, because of its fresher and more rising odor, also sharper, elegant and marked. This compound also appears to be clearly superior to the racemic methyl 1,4-dimethyl-3-cyclohexene-1-carboxylate known from the prior art, both from the standpoint of potency and of olfactory quality. Indeed, the odor of the last-mentioned compound was made heavier by the olfactory contribution of the other diastereomer of formula (Ib), so that its odor note was clearly less elegant and fresh, and less rising too, than that methyl (+) - (R) -1,4-dimethyl-3-cyclohexene-1-carboxylate according to the present invention. Consequently, mixtures containing a preponderant amount of this diastereomer (la) are also preferred according to the invention.

Due to its olfactory qualities, the compound of formula (la), and its aforementioned mixtures, find wide use in fine perfumery as well as in functional applications, they also lend themselves well to the preparation of perfumes and toilet waters and to perfume of various articles such as soaps, bath or shower gels, deodorants, shampoos, cosmetic preparations, as well as de2

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CH 680 853 A5

tergents, textile conditioners and cleaning products. For these applications, the compound of the invention can be used either alone or as a mixture with other perfuming ingredients, solvents or adjuvants customary in perfumery.

When used in the preparation of perfume compositions, the compound (la) or mixtures containing a predominant amount of this compound can be added in concentrations varying over a wide scale. Mention may be made, for this purpose, of concentrations of 1 to 10%, or even 20% by weight, relative to the weight of the composition. These values are quoted only by way of indication, the person skilled in the art knowing from experience that such concentrations depend both on the desired perfuming effect and on the nature of the other perfuming ingredients in a given composition. On the other hand, these concentrations can be much lower than the values cited when using the compounds according to the invention for the perfuming of the various articles mentioned above.

The compounds of formulas (la) and (Ib) are prepared according to a process consisting in subjecting to a transesterification reaction, using an alkali metal alkoxide, a lactone of formula

This transesterification reaction is carried out under conventional conditions, for example, using sodium methylate. Other alkali metal alkoxides can also be used for this purpose. The specific reaction conditions are described in the preparation examples presented below.

The lactones of formulas (IIa) and (IIb), used as starting materials in this process, can be prepared according to a process analogous to that described by T. Poil et al. in Tetrahedron Lett. 26, 3095 (1985), and which can be represented by the following diagram:

respectively

(lia)

(IIb)

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CH 680 853 A5

Diagram I

(R)

♦ r o

X

AlCis

D-pantolactone

+

59%

41%

(IIb)

(He has)

The above-mentioned authors have in fact shown that the Diels-Alder type addition of D-pantolactone acrylate to isoprene, catalyzed by Lewis acid, promotes the formation of the diastereomer of configuration S in position 1 of the cycle hexagonal, with a diastereofacia selectivity of almost 100%. According to the process represented in scheme I, the D-pantolactone methacrylate was reacted with isoprene, under the conditions described in the prior art. It was found that the diastereofacia selectivity was much lower, although the diastereomer of configuration S is always favored. The reaction was carried out in the presence of TiCU as a catalyst, but better results were obtained when using AlCb as Lewis acid.

The two iactones (IIa) and (IIb) can be separated from the mixture thus obtained, using conventional chromatographic techniques.

According to an alternative process, the compounds of formulas (IIa) and (IIb) can be prepared by the method shown schematically below:

Diagram n

DCC: dicyclohexyl carbodiimide DMAP: 4,4-dimethylaminopyridine

In this case, it is a condensation reaction which is catalyzed by 4,4-dimethylaminopyridine. The specific conditions of this reaction are described in detail below.

The lactones (IIa) and (IIb) can then be separated from the mixture by chromatography and obtained in the pure state by recrystallization from hexane.

DCC / CHjCtj

DMAP

(IIb)

(lia)

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CH 680 853 A5

The configuration of these starting lactones determines that of the desired esters of formula (la) or (Ib), the transesterification reaction which characterizes the process according to the invention being diastereoselective.

The invention will now be described in more detail with the aid of the preparation examples presented below, in which the temperatures are indicated in degrees centigrade and the abbreviations have the usual meaning in the art. The invention will also be illustrated using the example of application in perfumery presented below.

Example 1

Preparation of (-WSH .4-dimethvl-3-cvclohexene-1 -methylcarboxvlate and (+ HRV1.4-dimethvl-3-cvclohexene-1 -methylcarboxvlate

These two esters were prepared from the corresponding lactones, namely, (-) - (IR, 3'R) -1,4-dimethyl-3-cyclohexene-1-carboxylate of 4 'tetrahydro, 4'-dimethyl -2'-oxo-3'-furyle and (+) - (1S-3'R) -1,4-dimethyl-3-cyclohexene-1-carboxylate-4,4'-dimethyl-2'-oxo -3'-furyl, by heating at reflux of a mixture of the appropriate lactone with 2% sodium methylate in methanol. After the usual treatment, methyl (-) - (S) -1,4-dimethyl-3-cyclohexene-1-carboxylate was obtained with an optical purity of 95% and (+) - (R) -1 , Methyl 4-dimethyl-3-cyclohexene-1-carboxylate with an optical purity of 96%.

(-WSH .4-dimethvl-3-cvclohexene-1 -methylcarboxvlate [a] 20 ° D = -1 o, 2 ° (c = 2% in CHCI3)

NMR (H 360 MHz): 1.19 (s, 3H); 1.52-1.62 (m, 1H); 1.64 (s, 3H); 1.87 (broad d, 1H); 1.90-2.50 (m, 2H); 2.50 (Iarge d, 1H); 3.67 (s, 3H); 5.32 (s, H) Sppm.

SM: 168 (8, M +), 109 (48), 108 (100), 93 (60), 68 (36), 67 (40)

f + HRÌ-1 4-dimethvl-3-cvclohexene-1-methvlcarboxvlate

[a] 20 ° D = -11.8 ° (c = 2% in CHCI3)

The other analytical data for this compound are identical to that of its methyl isomer {-) - (S) -1,4-di-methyl-3-cyclohexene-1-carboxylate.

The aforementioned Iactones, used as starting materials, were prepared as follows:

a) By the process represented in diagram I

In a flask, 25 g of D-pantolactone and 29.2 g of triethylamine in 240 ml of methylene chloride were mixed, with stirring and at -24 °, and then added dropwise over 1 hour. , 7 g of methacryloyl chloride. After 4.5 h of stirring, the reaction mixture was washed with an aqueous 1N HCl solution (135 ml), with a solution of sodium bicarbonate and water. After concentrating and distilling, 99% pure D-pantolactone methacrylate was obtained.

P. eb. 83 ° / 13.3 Pa

[a] 20 ° o = -5 ° (c = 6.6% in CHCI3)

20 g of the ester prepared above and 0.33 g of aluminum chloride in toluene (6.2 ml) were heated at 60 ° in a sealed tube for 1 h. 7.5 g of isoprene was added all at once and the sealed tube was heated at 60 ° for 8 days. After washing and concentration, the residue was chromatographed ("flash") on siiica gel, all the fractions containing the reaction product having been combined. The gas chromatogram showed only two peaks in a proportion of about 60:40. The subsequent transesterification of this mixture, however, showed that it contained, in addition to the two desired lactones, approximately 10% in total of their 1,3-dimethyl-3-cyciohexene-1-carboxyla-te-tetrahydro-4 'isomers, 4'-dimethyl! -2'-oxo-3'-furyl. The two desired lactones could be separated by several successive chromatographic elutions.

b) By the process represented in diagram II

20 g of 1,4-dimethyl-3-cyclohexene-1-carboxylic acid [prepared by reaction of isoprene with methyl methacrylate; the product (168 g) was heated at reflux with potassium hydroxide (140 g) in ethanol (1.4 I) for 17 h, then acidified extracted with ether and concentrated; two successive recrystallizations from hexane allowed the acid to be obtained at 99% purity

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(p. 68 to 69 °)] in 30 ml of methylene chloride, 16.8 g of D-pantolactone, 29.5 g of dicyclohexyl carbodiimide and 2.7 g of 4,4-dimethylaminopyridine. The mixture was heated at reflux for 48 h, then washed with sulfuric acid and water, dried and concentrated. A mixture of the two lactones (IIa) and (IIb) was obtained, which was carefully chromatographed on a silica gel column, using a 7: 3 mixture of cyclohexane / ether as eluent, to enrich the first lactone fraction (IIa). and the subsequent lactone (IIb) fractions.

After several chromatographic purifications and crystallization of each of these products in hexane, the lactone of formula (IIa) was obtained at 94% purity and the lactone of formula (IIb) at 96% purity. Their analytical data were as follows:

(-H1 R.3'RÌ-1.4-dimethvl-3-cvclohexene-1 -carboxvlate of tetrahvdro-4'.4'-dimethvl-2, -oxo-3 / -furvle p. F .: 70-71 "

[<x] 20 ° d = -3.5 ° (c = 2% in CHCI3)

NMR (H 360 MHz): 1.10 (s, 3H); 1.17 (s, 3H); 1.28 (s, 3H); 1.64 (8.3H); 1.93 (d, 1H); 2.56 (d, 1H); 5.36 (s, 1H) 8ppm.

SM: 266 (2, M +), 109 (35), 108 (100), 106 (17), 93 (40), 67 (20)

(+) - (1 S.3'RV1.4-dimethvl-3-cvclohexene-1 -carboxvlate of tetrahvdro-4 / .4'-dimethvl-2'-oxo-3 / -furvle m.p .: 48-49 °

[cc] 20 ° d = + 4.2 ° (c = 2% in CHCI3)

NMR (1H, 360 MHz): 1.13 (s, 3H); 1.20 (s, 3H); 1.29 (s, 3H); 1.65 (s, 3H); 1.96 (d, 1H); 2.56 (d, 1H); 5.35 (s, 1H) 8ppm.

SM: 266 (2, M +), 109 (35), 108 (100), 106 (17), 93 (40), 67 (20)

Example 2

Preparation of a perfume composition

A basic perfume composition was prepared by mixing the following ingredients:

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CH 680 853 A5

Ingredients

Parts by weight

Isobornyl acetate

220

A-hexylcinnamic aldehyde

100

P-tert-butyl cyclohexyl acetate

100

Distilled limonene

80

l-distilled limonene

60

10% methyl nonyl aldehyde *

60

Phenylhexanol

40

Vertofix heart1 *

40

Siberian pine essence

40

Exaltex®2)

40

Menthol

40

a-Methyiionone

30

Essence of Resin Galbanum

20

10% parmantheme *

20

Hydratropic alcohol

20

Sagebrush essence

20

2,4-Dimethyl-3-cyclohexene-1-carbaldehyde

10

Rhubofix®3)

.10

Essence of synthetic galbanum

5

ß-Damascone at 50% *

5

Total

960

* in dipropylene glycol (DIPG)

origin: International Fiavors and Fragrances, USA 2 'cydopentadécanolide; origin: Firmenich SA, Geneva, Switzerland 3) 3 ', 4-dimethyl-tricycio [6.2.1.C?, 7] undec-4-ene-9-spiro-2'HDxirane; origin: Firmenich SA, Geneva, Switzerland

With this basic composition, three compositions A, B and C were prepared by mixing the following ingredients:

Ingredients (parts by weight) ABC

Basic composition 960 960 960

DIPG 40 -

Methyl (+) - (R) -1,4-dimethyl-3-cyclohexene-1-carboxylate - 40 - (-) - (S) -1,4-dimethyl-3-cyclohexene-1-carboxylate - - 40

Three identical samples of foaming bath gel were prepared with the following ingredients and according to the method described below:

Ingredients section%

AT

Texapon®1) N25

65.00

Comperlan®1 'KD

3.00

B

Distilled water

31.36

Sodium chloride

0.50

Citric acid

0.04

Nipagin®2 'MNA

0.10

1) origin: Henkel

2) origin: NIPA

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The ingredients in part A were mixed. The sodium chloride and Nipagin® MNA were dissolved in distilled water and then citric acid was added. Part B thus prepared was poured, little by little, onto part A, stirring slowly to avoid incorporating air.

The three bubble bath samples were perfumed with the perfuming compositions A, B and C respectively in an amount of 3% by weight of composition, relative to the total weight.

These three perfumed samples were blindly evaluated for comparison by a panel of expert perfumers. By a large majority, they preferred the sample scented with the help of composition B. In their opinion, this sample had a fragrant note much fresher and rising, and also richer, than that of the other two samples. Indeed, the perfumers have found that composition B could even be used in a concentration lower than that of compositions A and C, without noticing a loss of power in the perfume effect imparted by composition B to the sample of bath gei.

Furthermore, a comparison test of the same type was carried out between a sample of foaming bath perfumed with composition B and a sample of foaming bath perfumed using a similar composition, in which the (+) - (R ) -1,4-methyl dimethyl-3-cyclohexene-1-carboxylate had been replaced by the corresponding racemic mixture. The perfumers again preferred the perfumed sample using composition B for the freshness and the richness of its odor.

Claims (6)

Claims Methyl 1.1,4-dimethyl-3-cyclohexene-1-carboxylate in the form of the optically active diastereomer of formula or of a mixture containing a preponderant amount of this diastereomer. 2. Use of a compound of formula (la) or of any mixture containing a preponderant amount of this compound, as a perfuming ingredient. 3. Perfuming composition containing as a perfuming ingredient a compound of formula (la), or a mixture containing a preponderant amount of this compound. 4. Perfumed article containing as a perfuming ingredient a compound of formula (la), or a mixture containing a preponderant amount of this compound. 5. As a perfumed article according to claim 4, a perfume or eau de toilette, a soap, a shower or bath gel, a shampoo, a cosmetic preparation, a body or air deodorant, a detergent or textile conditioner, or a cleaning product. 6. Process for the preparation of a compound of formula (Ia), characterized in that a transesterification reaction is carried out, using an alkali metal alkoxide, a lactone of formula O (+) - (R) (the) (lia) 8