ES2303477B1 - NEW MOLECULA WITH ODOR SANDALO TYPE, PROCEDURE FOR ITS PREPARATION AND USE OF THE SAME AS AN ODORANT. - Google Patents

Abstract

New molecule with sandalwood smell, procedure for its preparation and use as odorant

The present invention relates to a new odorant 1, its preparation from (1 R ) - (-) - nopol (2) and its usefulness as a sandalwood ingredient in the production of perfume compositions. Obtaining 1 from 2 is achieved in 5 stages with an overall yield of 25%, by means of the following transformations: (a) catalytic hydrogenation, (b) oxidation to aldehyde of the hydroxyl group, (c) aldol condensation of the resulting aldehyde with butanone, (d) deconjugation and? -methylation of the aldol condensation product, and (e) reduction of carbonyl group.

Description

       \ global \ parskip0.930000 \ baselineskip
    

New molecule with sandalwood smell, procedure for its preparation and use as odorant

Object of the invention

The present invention relates to a new sandal-type odorant molecule of formula 1 or (2 R / 2 S ) - ( E ) -3,3-dimethyl-5 - ((1 S , 2 S , 5 S ) -6, 6-dimethylbicyclo [3.1.1] hept-2-yl) pent-4-en-2-ol, to its preparation procedure from (1 R ) - (-) - nopol 2 and to its use in the preparation of Perfume compositions

one

Background of the invention

Sandalwood essential oil, obtained by hydrodistilation of the wood and roots of the Santalum album L. shrub, native to eastern India, is one of the oldest and most appreciated by perfumers [G. Fráter, JA Bajgrowicz and P. Kraft, Tetrahedron 1998 , 54 , 7633-7703]. In addition to playing an important role in the Indian religion, it is highly prized in South Asia for its therapeutic and antiseptic properties [H. Okugawa, R. Ueda, K. Matsumoto, K. Kawanishi and A. Kato, Phytomedicine 1995 , 2 , 119-126]. From the point of view of the perfume industry, it is one of the most widely used raw materials due to the stability of its composition, its properties as a fixative and its floral, sweet, warm, woody, tenacious, spicy and musky notes [ KH Shankaranarayana and K. Parthasarathi, Perfum. Flavor 1984 , 9 , 17-20].

The (-) - ( Z ) -? -Santalol (3) (see Fig. 1), one of the main constituents of sandalwood essential oil, is considered as the main responsible for the sandalwood olfactory note [G. Ohloff, B. Winter and C. Fehr, in Perfumes. Art, Science and Technology , PM Müller and D. Lamparsky (editors). Elsevier Applied Science: London, 1991; 287-330]. The structure of santalol (3) consists of a bicyclic and bulky fragment, separated from the hydroxyl function by a hydrocarbon chain of 5 carbon atoms.

\euro

el litro, dependiendo de su origen y calidad, por lo que los perfumistas han tenido que confiar en sustitutos sintéticos más accesibles y de mejor precio. Entre ellos, dos tipos de compuestos han sido comercialmente exitosos, los terpenilciclohexanoles, por ejemplo (4) (véase Fig. 1) [J.R. Byers, Am. Perf. Essent. Oil Rev. 1947, 49, 483-484; E. Demole, Hely. Chim. Acta 1964, 47, 319-338; E. Demole, ibid. 1969, 52, 2065-2085], y los derivados de aldehído canfolénico (5) (véase Fig. 1). Dentro de este segundo grupo, el Polysantol® (6) (véase Fig. 1) es el más caro y también el más apreciado por los perfumistas debido a sus excelentes características olfativas y técnicas (umbral olfativo, presión de vapor, sustantividad, naturalidad, estabilidad,...). Por tanto, es evidente que su síntesis ya ha sido abordada y patentada mediante la utilización de diversos métodos [C. Chapuis y P.-A. Blanc (Firmenich S.A.), EP 0694520, 1994; T. Markert, V. Porrmann y K. Bruns (Henkel), WO 9321142, 1992; K.H. Schulte-Elte, B. Muller y H. Pamingle (Firmenich S.A.), EP 155591, 1984]. Probablemente, la síntesis más directa es la que parte de \alpha-pineno (7) (véase Fig. 1), el cual, por transposición ácida de su epóxido, se convierte estereoselectivamente en aldehído canfolénico (5) (véase Fig. 1). Los siguientes pasos hasta llegar a obtener Polysantol consisten en una condensación aldólica de 5 y butanona, desconjugación y \alpha-metilación de la enona resultante, y reducción del grupo carbonilo resultando Polysantol (6).This natural product was immediately the subject of numerous attempts at total synthesis [E.-J. Brunke and E. Klein, Chemistry of Sandalwood Fragrance, in Fragrance Chemistry , ET Theimer (Editor), Academic Press, Orlando, 1982, pp. 397-431]. Unfortunately, natural essential oil began to be scarce and more expensive since 1974. Its current market price is around 800

 \euro 

the liter, depending on its origin and quality, so that perfumers have had to rely on more affordable and better priced synthetic substitutes. Among them, two types of compounds have been commercially successful, terpenylcyclohexanols, for example (4) (see Fig. 1) [JR Byers, Am. Perf. Essent Oil Rev. 1947 , 49 , 483-484; E. Demolish, Hely. Chim. Act 1964 , 47 , 319-338; E. Demolish, ibid . 1969 , 52, 2065-2085], and the derivatives of cannibalic aldehyde (5) (see Fig. 1). Within this second group, Polysantol® (6) (see Fig. 1) is the most expensive and also the most appreciated by perfumers due to its excellent olfactory and technical characteristics (olfactory threshold, vapor pressure, substantivity, naturalness, stability,...). Therefore, it is clear that its synthesis has already been addressed and patented through the use of various methods [C. Chapuis and P.-A. Blanc (Firmenich SA), EP 0694520, 1994 ; T. Markert, V. Porrmann and K. Bruns (Henkel), WO 9321142, 1992 ; KH Schulte-Elte, B. Muller and H. Pamingle (Firmenich SA), EP 155591, 1984 ]. Probably, the most direct synthesis is that part of α-pinene (7) (see Fig. 1), which, by acid transposition of its epoxide, is stereoselectively converted to canniphenic aldehyde (5) (see Fig. 1) . The next steps to obtain Polysanthol consist of an aldol condensation of 5 and butanone, decongestion and? -Methylation of the resulting enone, and reduction of the carbonyl group resulting in Polysantol (6).

Similarly, the structure-odor relationships of Polysanthol and other derivatives of cannibalic aldehyde have been the subject of multiple studies [G. Buchbauer, H. Spreitzer, F. Zechmeister-Machhart, A. Klinsky, P. Weiss-Greiler and P. Wolschann, Eur. J. Med. Chem . 1998 , 33 , 463-470; G. Buchbauer, I. Stappen, C. Pretterklieber and P. Wolschann, Ibid . 2004 , 39 , 1039-1046; B. Hölscher, NA Braun, B. Weber, C.-H. Kappey, M. Meier and W. Pickenhagen, Hely. Chim. Minutes 2004 , 87 , 1666-1680].

Since the structure of the olfactory receptors and the mechanism of interaction between them and the molecules responsible for the odor is still to some extent unknown, the determination of the correct olfactory phosphorus associated with each olfactory sensation has to be done following molecular similarity studies with those responsible compounds of smell and other related toilets. With all this information and to date [G. Buchbauer, A. Hillisch, K. Mraz and P. Wolschann, Helv. Chim. Acta 1994 , 77 , 2286-2296] it is known that three osmoforic centers, located in Polysantol (6) (and in santalol (3)), are important for olfactory printing. a hydroxyl group, a lipophilic substituent neighboring OH and a rigid and bulky group several carbon atoms apart. Although it is accepted that with the first two osmophors there is little room for improvement, it is known that the third, the rigid and bulky fragment, still allows structural modifications, judging by the variety described in this fragment.

       \ global \ parskip1.000000 \ baselineskip
    

Molecules with good olfactory results described in the literature are, for example, alcohols 8 [B. Auger, JA Bajgrowicz, and E. Giraudi (Givaudan), WO 9311094, 1991 ], 9 [C. Chapuis (Firmenich), EP 572797, 1992 ], 10 [AS Dimoglo, AA Beda, NM Shvets, MY Gorvachov, LA Kheifits and IS Aulchenko, New J. Chem . 1995 , 19 , 149-154], 11 [U. Wahren, I. Sprung, K. Schulze, M. Findensen and G. Buchbauer, Tetrahedron Lett . 1999 , 40 , 5991-5992], 12 [S. Ono, J. Etsuno, K. Fukuda, S. Toi and Y. Fujikura (Kao), JP 7165655, 1993] and 13 [K. Schulze and H. Uhlig, Monatsh. Chem 1989 , 120 , 547-559]. All referenced molecules are shown in Figure 1.

Although there are several speakers Sandalwood synthetic types commonly used in processing of perfume compositions, there is still a need for look for new molecules that allow to expand the "palette of perfumer "and that allow to find better approaches to Smell of natural sandalwood oil.

Summary of the invention

The present invention describes the process of obtaining a new sandalwood odorant, the (2 R / 2 S ) - ( E ) -3,3-dimethyl-5 - ((1 S , 2 S , 5 S ) - 6,6-dimethylbicyclo [3.1.1] hept-2-yl) pent-4-en-2-ol (1) from (1 R ) - (-) - nopol (2), the result of the evaluation olfactory thereof and spectroscopic data that define its chemical structure.

The nopol 2 starting product, also called homomirtenol, is a viscous, colorless and immiscible liquid in water, with an olfactory description of a sweet and citrus smell of pine wood with hints of a bizarre. For the development of the present invention 98% pure commercial nopol is used, which is catalytically hydrogenated to give (1 S , 2 S , 5 S ) -dihydronopol (14) (see Fig. 1), various catalysts can be used metallic, for example of the Ni-Raney, Pd (C) or Adams (PtO2) [W. Heitmann and U. Mätzel (Kali-Chemie Pharma GmbH), EP 0406742, 1989 ].

The primary alcohol 14 is then treated with an oxidant type Cr (VI) salts, such as Collins , Corey reagents or pyridinium dichromate (PDC) [KB Sharpless and K. Akashi, J. Am. Chem. Soc . 1975 , 97 , 5927-5928; EJ Corey and JW Suggs, Tetrahedron Lett . 1975 , 2647-2650; EJ Corey and G. Schmidt, Tetrahedron Lett . 1979 , 5 , 399-402], although the CrO3 / HMPA system or the oxidation of Oppenauer with aluminum t- butoxide and acetone or butanone can also be used [G. Cardillo, M. Orena and S. Sandri, Synthesis 1976 , 394-396; C. Djerassi, Org. React . 1951 , 6 , 207-272], to obtain compound 15 (see Fig. 1).

Subsequently, 15 is subjected to aldol condensation with butanone in basic medium [KH Schulte-Elte, B. Muller and H. Pamingle (Firmenich SA), EP155591, 1984 ]. Alternatively, the preformed enolate with metals such as Mg PM Castro, PJ Linares-Palomino, S. Salido, J. Altarejos, M. Nogueras and A. Sánchez, Tetrahedron Lett can be used . 2004 , 45 , 2619-2622] or other divalent metals [JR Stille and RH Grubbs, J. Am. Chem. Soc . 1983 , 105 , 1664-1665; DA Evans and LR McGee, Tetrahedron Lett . 1980 , 21 , 3975-3978; DA Evans and LR McGee, J. Am. Chem. Soc . 1981 , 103 , 2876-2878]. In this way, 16 is obtained (see Fig. 1), whose epider in C2 'has a powerful sandalwood aroma, with floral, sweet and animal tones [BD Mookherjee, RW Trenkle, RK Wolff, RM Boden and T. Yoshida (IFF ), US 4428387, 1982 ], which can be used to increase and enhance the aroma of tobacco. Next, the α, β-unsaturated ketone 16 is transformed into the β, γ-unsaturated ketone (17) (see Fig. 1) by treatment with base and a methyl halide. As a base, potassium t- butoxide can be used in polar solvents, such as DMF or t- butanol, and as a methyl halide, anyone except fluorine can be used [JM Castro, PJ Linares-Palomino, S. Salido, J. Altarejos , M. Nogueras and A. Sánchez, Tetrahedron 2005 , 61 , 11192-11203; RE Naipawer (Givaudan), EP 0203528, 1985 ; JA Bajgrowicz and G. Fráter (Givaudan), EP 0841318, 1996 ]. Finally, the reduction of 17 with metal hydrides, such as sodium borohydride, or by reduction of Meerwein-Ponndorf-Verley [CF de Graauw, JA Peters, H. van Bekkum and J. Huskeus, Synthesis 1994 , 10 , 1007-1017 ], leads to the obtaining of compound 1, object of this invention, with an overall yield around
25%

The olfactory analysis of compound 1 indicates that It has a clean note of natural sandalwood, woody, something green type Moss and citrus, with a somewhat animal finish, vanilla and cresolic. These olfactory characteristics of compound 1, closer to the of natural sandalwood oil than of synthetic odorants type Polysantol®, give this new molecule an interesting value in the production of perfume compositions.

Figure 1 shows all the molecules referenced above and in what follows here description of the invention

Description of the invention

The preparation of the new molecule according to the invention, (2 R / 2 S ) - ( E ) -3,3-dimethyl-5 - ((1 S , 2 S , 5 S ) -6,6-dimethylbicyclo [3.1. 1] hept-2-yl) pent-4-en-2-ol (1), from (1 R ) - (-) - nopol (2), is performed in 5 stages with a 25% yield.

All compounds obtained in the sequence synthetic that is described to obtain the new molecule 1 is structurally determined based on the techniques usual spectroscopic specimens (IR, low and high resolution MS, NMR of 1 H, 13 C and two-dimensional, such as COZY, NOESY, HMBC and HSQC).

Each stage can be carried out as described below.

The (1 R ) - (-) - nopol (2) dissolved in absolute MeOH (0.12M) is subjected to catalytic hydrogenation using PtO2 (molar ratio 2: PtO2 of 15: 1) and a pressure of H2 of 1-2 atm. The reaction is carried out at room temperature and with vigorous stirring for 90 min and, after filtration of the catalyst and evaporation of the solvent, 14 is obtained in a yield of 90%. The NMR signals of some of the hydrogen in the bicyclo [3.1.1] heptan-2-yl cluster of 14 are overlapping, making it difficult to make unambiguous assignments. For this reason it was necessary to apply all the usual spectroscopic techniques in NMR and other more specific ones, such as that of double irradiation decoupling, in order to help obtain unequivocal structural and conformational conclusions, thus confirming that the compound 14 obtained corresponds to the cis isomer of dihydronopol, that is, 2 - ((1 S , 2 S , 5 S ) -6,6-dimethylbicyclo [3.1.1] hept-2-yl) ethanol [K.-Y. Kim and S.-G. Lee, Magn. Reson Chem 1997 , 35 , 451-454; EC Sen and RA Jones, Tetrahedron 1972, 28, 2871-2876; AY Badjah-Hadj-Ahmed, BY Meklati, H. Waton and QT Pham, Magn. Reson Chem 1992 , 30 , 807-816]. The oxidation of alcohol 14 can be carried out by adding a freshly prepared solution of PDC in dichloromethane (0.4M) over a solution of 14 in the same solvent (0.7M) at 25 ° C and for 20 hours.

The conversion of 14 into aldehyde 15, 2 - ((1 S , 2 S , 5 S ) -6,6-dimethylbicyclo [3.1.1] hept-2-yl) acetaldehyde, is complete, and the reaction yield It is 75%. The aldehyde 15 side chain can be increased by 4 more carbon atoms by two-step aldol condensation: (a) aldol reaction of 15 with butanone and KOH in MeOH, (b) dehydration of the aldoles obtained by acid azeotropic distillation with p - TsOH For the aldol reaction, a solution of aldehyde 15 in MeOH (6M) is added, within 30 min, to a solution of butanone in MeOH and KOH (molar ratio 15: butanone: KOH, 1: 4: 0.04 ) previously stirred at 0 ° C for 1 hour.

After the reaction, the crude is subjected to azeotropic distillation with the help of a Dean-Stark type water trap and a catalytic amount of p- TsOH. After purification, enone 16, ( E ) -3-methyl-5 - ((1 S , 2 S , 5 S ) -6,6-dimethylbicyclo [3.1.1] hept-2-yl) pent-3- is obtained en-2-one, with a yield of 56%.

The conversion of 16 into 17 is carried out by deconjugation reaction and? -Methylation. For this, a solution of 16 in DMF (15M) is added, dropwise, onto another stirred solution of K t BuO in DMF (2M) (16: K t BuO molar ratio, 1: 1 , 1) for 30 min. The addition of MeI (molar ratio 16: MeI from 1:10) at 0 ° C allows obtaining the β, γ-unsaturated ketone 17, ( E ) -3,3-dimethyl-5 - ((1 S , 2 S , 5 S ) -6,6-dimethylbicyclo [3.1.1] hept-2-yl) pent-4-en-2-one, with a yield of 85% after purification. Finally, the ketone 17 can be reduced to alcohol 1 by treatment with NaBH 4 in MeOH (molar ratio 17: NaBH 4 of 1: 1.5) at 0 ° C.

Purification of the reaction crude allows obtaining 1, (2 R / 2 S ) - ( E ) -3,3-dimethyl-5 - ((1 S , 2 S , 5 S ) -6,6-dimethylbicyclo [3.1. 1] hept-2-yl) pent-4-en-2-ol, with a yield of 77% after purification.

The olfactory evaluation of compound 1 is performed (a) by impregnating mouillette strips with the sample and describing its smell at first, after 3 hours and at 24 hours, (b) introducing the sample in a gas chromatograph equipped with a sniffing port and describing its smell at the exit of it.

Both analyzes allow to conclude that the compound 1 has sandalwood olfactory properties interesting, that make this new molecule an odorant of utility in the elaboration of compositions for perfumery.

       \ vskip1.000000 \ baselineskip
    

Examples of embodiment of the invention

Example one

A stirring mixture of 2 (250 mg, 1.5 mmol), PtO2 (23 mg) and absolute MeOH (13 ml) is subjected to a pressure of H2 from 1 to 2 atmospheres at room temperature for 1.5 h. The crude is filtered and the solvent is evaporated, obtaining 14 (227 mg, 90%) in the form of a colorless oil.

quad

IR: 3332, 2907, 1383, 1366 cm -1

quad

MS (70 eV): 168 (1%), 150 (1%), 135 (5%), 123 (14%), 107 (33%)

quad

1 H NMR (CDCl 3, 400 MHz): 3,653 ( dt , J 1A-1B = 10.1 Hz; J 1A-2A-2B = 7.0 Hz, 1H, H-1A ), 3,623 ( dt , J 1A-1B = 10.1; J 1A-2A-2B = 7.0, 1H, H-1 B), 1,677 ( q , J 2-2'-1 = 7.0 Hz, 2H, CH 2} {-2), 1870-1822 (m, 1H, CH-1 '), 2.124 (ddq, J _ {2'-3'-2-} = 7.1 Hz; J 2'-3's = 11.0 Hz; J 2'-1 '= 2.0 Hz, 1H, CH-2'), 1,474 ( ddt , J 3'a-3's = 14.2 Hz; J 3'a-2'-4's = 5.8 Hz; J 3'a-4'a = 11.1 Hz, 1H, CH-3'a), 2.005-1.920 ( m , 1H, CH-3's ), 1.890-1.822 ( m , 1H, CH-4'a), 1.965-1.896 ( m , 1H, CH-4's), 1.910-1.870 ( m , 1H, CH-5 '), 0.900 ( d , J _ {7's-7'a} = 9.5 Hz, 1H, CH-7's), 2,329 ( ddt , J 7'a-7's = 9.3; J 7'a-4'a = 2.0; J _ {7'a-1'-5 '} = 6.2, 1H, CH-7'a), 1,186 ( s , 3H, CH 3 -8'), 1,013 ( s , 3H, CH 3 -9 ').

       \ vskip1.000000 \ baselineskip
    

Example 2

A solution of 14 (907 mg, 5.4 mmol) in Dry CH 2 Cl 2 (8 ml) is added to a stirred solution of PDC (3.05 g, 8.1 mmol) in CH 2 Cl 2 (22 ml) under atmosphere of argon at 25 ° C for 20 h. The mixture is diluted with hexane-Et2O, the solvent is filtered and evaporated, obtaining 15 (672 mg, 75%) in the form of yellow oil pale:

quad

IR: 2907, 2713, 1725, 1384, 1367 cm -1

quad

1 H NMR (CDCl 3, 400 MHz): 0.904 ( d , J 7's-7'a = 9.8 Hz, 1H, CH-7's), 0.947 ( s , 3H, Me-9 '), 1,115 ( s , 3H, Me-8'), 1,368 ( m , 1H, CH-3'a), 1,994 ( ddt , J 3's-3'a) = 14.6 HZ, J 3's- 4'a} = 3.0 HZ, J 3's-4's-2 '= 10.4 Hz, 1H, CH-3's), 1,735-1,785 ( m , 1H, CH-1'), 1,730-1,920 ( m , 2H , CH2-4 '), 1,910-1,890 ( m , 1H, CH-5'), 2,284 ( ddt , J 7'a-7's) = 9.3 Hz, J 7'a-4'a = 2.0 Hz, J 7'a-1'-5 '= 6.0 Hz, 1H, CH-7'a), 2.435 ( ddd , J 2A-1 = 2.0 Hz; J 2A-2B = 16.3 Hz; J 2A-2 '= 7.3 Hz, 1H, CH-2A), 2.467 ( ddd , J 2B-1 = 2.0 Hz; J 2A-2B = 16.3 Hz; J 2B-2 '= 7.3 Hz, 1H, CH-2B), 2,582 ( ddt , J 2'-2 = 7.3 Hz; J 2'-3's = 17.1 Hz; J 2'-1} = 2.3 Hz, 1H, CH2-2 ').

       \ vskip1.000000 \ baselineskip
    

Example 3

A solution of 15 (996 mg, 6.0 mmol) in MeOH (1 ml) is added to a stirred solution of butanone (1.73 g, 24.0 mmol) and KOH (15 mg, 0.25 mmol) in MeOH (1.5 ml) at 0 ° C for 1 h. The mixture is kept under stirring at room temperature for 8 h, an aqueous solution of 1N AcOH (100 ml) is added, the solvent is partially evaporated and the resulting crude is diluted with Et2O (25 ml), washed with an aqueous solution of 1N AcOH (25 ml) and brine (3 x 25 ml). The organic phase is dried over anhydrous Na2SO4 and the solvent is evaporated to give a yellow residue, to which dry toluene (10 ml) and p -TsOH (40 mg, 0.2 mmol) are added. The mixture is refluxed for 1.5 h using a Dean-Stark type water trap. The mixture is allowed to cool and washed with a saturated aqueous solution of NaHCO3 (3 x 25 ml), with a 1N aqueous solution of AcOH (25 ml) and with brine (3 x 25 ml). The organic phase is dried over anhydrous Na2SO4 and the solvent is evaporated, yielding 16 crude, which is purified by silica gel column chromatography to give pure 16 (739 mg, 56%) as of yellow oil:

quad

IR: 2982, 2907, 1669, 1641, 1468, 1431, 1387, 1365 cm -1

quad

MS (70 eV): 220 (1%), 205 (9%), 177 (13%), 137 (7%), 123 (27%), 83 (20%), 43 (86%)

quad

1 H NMR (CDCl 3, 400 MHz): 2,298 ( s , 3H, CH 3 -1), 1,766 ( q , J Me-3-4 = 1.1 Hz, 3H, CH 3 -C3), 6,618 ( tq , J 4-5 = 7.3 and J 4-Me-3 = 1.3 Hz, 1H, CH-4), 2,353-2,301 ( m , 2H, CH 2 -5), 1,883-1826 ( m , 1H, CH-1 '), 1,955-1,895 ( m , 1H, CH-2'), 1,499 ( ddt , J 3'a-3's) = 14.5, J 3'a-4'a = 11.5, J 3'a-4's-2 '= 5.9 Hz, 1H, CH-3'a), 2,042-1,932 ( m , 1 H, CH-3's), 1910-1853 (m, 1H, CH-4'a), 2003-1915 (m, 1H, CH-4's), 2.187 (ddt, J 5'- {1 '} = 2.0, J 5'-7'a = 2.6, J 5'-4's-4'a} = 7.4 Hz, 1H, CH-5 '), 1.070 ( s , 3H, CH 3 -9') , 1,196 ( s , 3H, CH 3 -8), 0.894 ( d , J 7's-7'a = 9. Hz, 1H, CH-7's), 2,389-2,322 ( m , 1H, CH- 7'a).

       \ vskip1.000000 \ baselineskip
    

Example 4

A solution of 16 (13.31 g, 60.5 mmol) in DMF Dry (4 ml) is added to a stirred solution of K t BuO (6.98 g, 61.0 mmol) in dry DMF (30 ml) at 25 ° C for 0.5 h. Mix stir another 10 minutes, cool to 0 ° C and Mel is added thereto (22.81 g, 160.7 mmol). After 10 minutes brine is added (10 ml) and an aqueous solution of 1N AcOH (10 ml), and the mixture is extract with hexane / Et 2 O 1: 1 (75 ml). The organic phase is washed with a 1 N aqueous solution of AcOH (2 x 30 ml) and brine (3 x 30 ml), dried over anhydrous Na2SO4, and the solvent is evaporated, obtaining 17 crude, which is purified by silica gel column chromatography, to give pure 17 (12.03 g, 85%) in the form of yellow oil:

quad

IR: 2939, 2909, 1710, 1672, 1383, 1364, 972 cm -1

quad

MS (70 eV): 234 (1%), 219 (1%), 191 (23%), 149 (15%), 93 (3%), 69 (100%), 43 (77%)

quad

1 H NMR (CDCl 3, 400 MHz): 2,080 ( s , 3H, CH3-1), 5,376 ( dd , J 4-5 = 15.8 and J 4-2 ') = 1.6 Hz, 1H, CH-4), 5.670 ( dd , J 5-4 = 15.8 and J 5.2 '= 6.8 Hz, 1H, CH-5), 1.910-1.990 ( m , 1H, CH-1 ') 1 2,733 ( ddddd , J 2'-3's = 10.5, J 2'-5 = 6.8, J 2'-1' = 6.0, J 2'-3'a = 2.5, J 2'-4 = 1.7 Hz, 1H, CH-2 '), 1,598 ( dddd , J 3'a-3's) = 15.3, J 3'a-4'a = 10.5, J 3'a-2 '= 6.0, J 3'a-4's = 4.5, 1H, CH-3'a), 1.936-2.022 ( m , 1H, CH-3's) , 1810-1919 (m, 1H, CH-4'a), 1920-2001 (m, 1H, CH-4's), 1865-1960 (m, 1H, CH-5 '), 0.995 (d, J { 7's-7'a} = 9.7 Hz, 1H, CH-7's), 2,324 ( dddd , J 7's-7'a = 9.7, J 7's-1 '= 6.6, J 7's-5 '= 5.7, J 7's-4'a = 1.6 Hz, 1H, CH-7'a), 1,189 ( s , 3H, CH3 -8), 0.948 ( s , 3H, CH_3 } -9), 1,189 ( s , 6H, 2CH3-C3).

       \ vskip1.000000 \ baselineskip
    

Example 5

Solid NaBH 4 (2.77 g, is added in portions) 71.8 mmol) to a stirred solution of 17 (12.80 g, 54.7 mmol) in MeOH (50 ml) at 0 ° C. After 15 minutes, the mixture is maintained under stirring at room temperature for 45 minutes, it is partially evaporates the solvent and the resulting crude is diluted with hexane / Et2O 1: 2 (75 ml) and neutralized with a solution 1 N aqueous AcOH at 0 ° C. The organic phase is washed again with a 1N aqueous solution of AcOH (50 ml) and with brine (3 x 50 ml), dried over anhydrous Na2SO4, and the solvent is evaporate, obtaining 1 crude, which is purified by chromatography on silica gel column, to yield 1 pure (9.94 g, 77%) in form of yellow oil:

quad

IR: 3475-3300, 2938, 2907, 1654, 1384, 1366, 1090, 1069, 975 cm -1

quad

1 H NMR (CDCl 3, 400 MHz): 1,086 ( d , J = 6.4 Hz, 3H, CH-1), 3,458 ( q , J = 6.4 Hz, 1H, CH-2), 5,295 ( dd , J 4-5 = 15.8 and J 4-2 '= 1.5 Hz, 1H, CH-4), 5.622 ( dd , J 5-4 = 15.8 and J 5 -2 '} = 7.0 Hz, 1H, CH-5), 1,897-1,988 ( m , 1H, CH-1'), 2,729 ( dtt , J 2'-1'-4 = 1.1, J _ 2'-3'a-5 = 6.0, J 2'-3's = 11.8 Hz 1H, CH-2 '), 1.606 ( ddt , J 3'a-4'a} = 5.6, J 3'a-3's = 10.2, J 3'a-2'-4's = 10.0 Hz, 1H, CH-3'a), 1.934-2.030 ( m , 1H, CH-3's), 1.808 -1,921 ( m , 1H, CH-4'a), 1,922-1,997 ( m , 1H, CH-4's), 1,860-1,968 ( m , 1H, CH-5 '), 0.989 ( d , J 7's- 7'a} = 9.9 Hz, 1H, CH-7's), 2,323 (dt, J 7's-7'a} = 8.8 and J 7'a-1'-5 '= 6.1 Hz, 1H, CH-7'a), 1,189 ( s , 3H, CH 3s-C-6), 0.969 ( s , 3H, CH 3s-C-6), 0.969 ( s , 3H, CH 3 - C-3), 0.962 ( s , 3H, CH 3 '- C-3).

Claims (9)

1. New compound of systematic name (2 R / 2 S ) - ( E ) -3,3-dimethyl-5 - ((1 S , 2 S , 5 S ) -6,6-dimethylbicyclo [3.1.1] hept -2-il) pent-4-en-2-ol represented by formula 1 2 2. Method for obtaining the new compound of formula 1 according to claim 1 characterized in that it is obtained from (1 R ) - (-) - nopol (2), 3 by catalytic hydrogenation of 2 to give saturated alcohol 14, oxidation of 14 to the aldehyde 15, aldol condensation of 15 and butanone to give the ketone α, β-unsaturated 16, conversion of 16 into the ketone β, γ-unsaturated 17 by deconjugation and? -methylation, and reduction end of 17. 3. Method for obtaining the new compound of formula 1 according to claim 2 characterized in that in the catalytic hydrogenation of (1 R ) - (-) - nopol (2) to cause saturated alcohol 14, 2 - ((1 S , 2 S , 5 S ) -6,6-dimethylbicyclo [3.1.1] hept-2-yl) ethanol, a catalyst of the type Ni-Raney, PtO2, Pd (C) or the like is used. 4. Process for obtaining the new compound of formula 1 according to claim 2 characterized in that for the oxidation of saturated alcohol 14 to cause aldehyde 15, 2 - ((1 S , 2 S , 5 S ) -6,6-dimethylbicyclo [3.1.1] hept-2-yl) acetaldehyde, an oxidizing agent such as Cr (VI) salts or the like is used. 5. Method for obtaining the new compound of formula 1 according to claim 2 characterized in that for aldol condensation of aldehyde 15 to give the ketone?,? -Unsaturated 16, ( E ) -3-methyl-5 - (( 1 S , 2 S , 5 S ) -6,6-dimethylbicyclo [3.1.1] hept-2-yl) pent-3-en-2-one, butanone is used. Method for obtaining the new compound of formula 1 according to claim 2, characterized in that for the deconjugation and? -Methylation of the?,? -Unsaturated ketone 16 to originate the?,? -Unsaturated ketone 17, ( E ) -3,3-dimethyl-5 - ((1 S , 2 S , 5 S ) -6,6-dimethylbicyclo [3.1.1] hept-2-yl) pent-4-en-2-one, a basic treatment is carried out followed by the addition of a methyl halide. 7. Method for obtaining the new compound of formula 1 according to claim 2, characterized in that in the reduction of the β, γ-unsaturated ketone 17 to give the alcohol 1 a reducing agent selected from sodium borohydride, isopropoxide of aluminum or similar 8. A new compound of formula 1 according to claim 1 characterized in that it has olfactory properties that define it as a sandalwood odorant. 9. Use of the new compound of formula 1 according to claim 1 as an odorant useful in the preparation of compositions for perfumery.