Indane Derivatives for Malodor Counteraction

Abstract

The present invention relates to the field of malodor counteraction. More particularly, it concerns malodor masking ingredient having an indane moiety (as defined in formula (I)), as well as malodor masking compositions comprising such ingredients.

Claims

1. A method to modify, suppress, reduce, decrease or mask a toilet malodor comprising the step of releasing into the air or over a surface, or to the malodor source, an effective amount of at least a compound of formula ##STR00006## wherein n represents 1 or 2; R.sup.1 represents a hydrogen atom or a methyl or ethyl group; R.sup.2 represents a CH.sub.2OR.sup.7 or a R.sup.8CO group, R.sup.7 being a hydrogen atom or a C.sub.1-3 hydrocarbon group or a R.sup.8CO group, and R.sup.8 being a hydrogen atom or a C.sub.1-3 hydrocarbon group; R.sup.3 represents a hydrogen atom or a C.sub.1-4 hydrocarbon group or a C.sub.1-3 alkoxyl group; and each of R.sup.4, R.sup.5 and R.sup.6 represents, independently from each other, a hydrogen atom or a C.sub.1-3 alkyl group.

2. A method according to claim 1, characterized in that said compound (I) is a compound of formula ##STR00007## wherein n represents 1 or 2; R.sup.1 represents a hydrogen atom or a methyl group; R.sup.2 represents a CH.sub.2OR.sup.7 or a R.sup.8CO group, R.sup.7 being a hydrogen atom or a methyl or ethyl group or a R.sup.8CO group, and R.sup.8 being a methyl or ethyl group; R.sup.3 represents a hydrogen atom or a C.sub.1-4 alkyl group; and R.sup.4 represents a hydrogen atom or a methyl group.

3. A method according to claim 1 or 2, characterized in that said compound (I) is a compound of formula ##STR00008## wherein n represents 1 or 2; R.sup.1 represents a hydrogen atom or a methyl group; R.sup.9 represents a hydrogen atom or a methyl or ethyl group or a CH.sub.3CO group; and R.sup.3 represents a hydrogen atom or a methyl or ethyl group.

4. A method according to any one of claims 1 to 3, characterized in that said compound is a C.sub.11-13 compound.

5. A method according to any one of claims 1 to 4, characterized in that said compound is 2,5-dimethyl-2-indanemethanol, (2,5-dimethyl-2,3-dihydro-1h-inden-2-yl)methyl methyl ether, (2-methyl-2,3-dihydro-1h-inden-2-yl)methanol, (5-methyl-2,3-dihydro-1h-inden-2-yl)methanol, (2-methyl-2,3-dihydro-1h-inden-2-yl)methyl acetate, 1-(2,5-dimethyl-2,3-dihydro-1h-inden-2-yl)ethanone, (2,4,6-trimethyl-2,3-dihydro-1H-inden-2-yl)methanol and/or (2,6-dimethyl-1,2,3,4-tetrahydro-2-naphthalenyl)methanol.

6. A method according to any one of claims 1 to 5, characterized in that said toilet malodor is generated by the presence of skatole, C.sub.1-7 aliphatic carboxylic acids, methyl morpholines, thioglycolic acid, cresols, C.sub.1-4 dialkyl sulfide or disulfide or trisulfide, indole, and/or C.sub.1-7 thiols or mixtures thereof.

7. A method according to any one of claims 1 to 6, characterized in that said toilet malodor is generated by the presence of skatole, p-cresol, dimethyl sulfide or disulfide or trisulfide, indole, or mixtures thereof.

8. A compound of formula ##STR00009## wherein n represents 1 or 2; R.sup.1 represents a hydrogen atom or a methyl or ethyl group; R.sup.7 being a C.sub.1-3 hydrocarbon group; R.sup.3 represents a hydrogen atom or a C.sub.1-4 hydrocarbon group or a C.sub.1-3 alkoxyl group; and each of R.sup.4, R.sup.5 and R.sup.6 represents, independently from each other, a hydrogen atom or a C.sub.1-3 alkyl group; provided that 2-methoxy-2,3-dihydro-1H-indene is excluded.

9. A MOC composition comprising: i) as a MOC ingredient, at least one compound of formula (I), as defined in any one of claims 1 to 5; ii) at least one ingredient selected from the group consisting of a perfumery carrier and a perfumery base; and iii) optionally at least another MOC compound; and iv) optionally at least one perfumery adjuvant.

10. A MOC consumer product comprising, as an active ingredient, at least one compound of formula (I), as defined in any one of claims 1 to 5.

11. A MOC consumer product according to claim 10, characterized in that the MOC consumer product is selected amongst a fabric care product, a toilet paper or napkin, an air freshening product, a surface care product and/or a pet-litter.

12. A MOC consumer product according to claim 10, characterized in that the MOC consumer product is selected amongst: a fabric care product in the form of a liquid detergent, a powder detergent, detergent tablets, a detergent bar, a detergent paste, a liquid fabric softener, fabric softener sheets, a fabric scent booster, a laundry pre-treatment, a fabric refresher, an ironing water, a laundry bleach, a carpet powder or a carpet cleaner; an air freshening product in the form of an air freshener spray, a gel air freshener, a liquid-wick air freshener, a solid air freshener comprising a porous substrate, a liquid or gel air freshener comprising a permeable membrane, an electrically operated air freshener, and a dual purpose air freshener/disinfectant spray; and/or a surface care product in the form of an all-purpose cleaner, a furniture polish, a wood floor cleaner, a toilet care product.

Description

DESCRIPTION OF THE DRAWINGS

[0096] FIG. 1: Ca.sup.2+ imaging traces of individual indole-responsive olfactory sensory neurons and their inhibition to Compound 1, Compound 2 or Compound 3 (MOC) are shown in FIG. 1 plots (A, C, E). Inhibition of the population of indole-responsive olfactory sensory neurons is shown in FIG. 1 plots (B, D, F).

[0097] Open circles are individual olfactory neuron modulation values that lie outside 95.sup.th percentile.

[0098] FIG. 2: Radar graph reporting the duplicated assessment of 3 odor descriptors (Animal/Fecal/Tar, Pleasantness and Freshness) for indole alone (-: Indole alone) and indole combined to Compound 1 ( - - - : indole alone+Compound 1).

[0099] The invention's compounds can be prepared according to a method known in the literature, and the compounds of formula (V) can be obtained by a standard alkylation of the corresponding alcohol.

EXAMPLES

[0100] The invention will now be described in further detail by way of the following examples, wherein the abbreviations have the usual meaning in the art, the temperatures are indicated in degrees centigrade ( C.); the NMR spectral data were recorded in CDCl.sub.3 (if not stated otherwise) with a 360 or 400 MHz machine for .sup.1H and .sup.13C, the chemical shifts are indicated in ppm with respect to TMS as standard, the coupling constants J are expressed in Hz. [0101] 2,5-Dimethyl-2-indanemethanol (compound 1); 2-Methyl-2-indanemethanol (compound 3); 5-methyl-2-indanemethanol (compound 4); (2-Methyl-2,3-dihydro-1H-inden-2-yl)methyl acetate (compound 5); 5-ethyl-2-methyl-2-indanmethanol (compound 8); 5-isopropyl-2-methyl-2-indanmethanol (compound 12); 2,5,6-trimethyl-2-indanmethanol (compound 14); 2,4-dimethyl-2-indanmethanol (compound 15); 2,4,6-Trimethyl-2-indanemethanol (compound 16).

[0102] These compounds were synthesized according to the procedure reported in the publication Helv. Chim. Acta 2005, 88, 3118 and in patent EP 1022265.

[0103] 5-Tert-butyl-2-methyl-2-indanmethanol (compound 13):

[0104] This compound was synthesized according to the procedure reported in the publication Helv. Chim. Acta 2004, 87, 1767.

Example 1

Synthesis of Compounds of Formula (I)

()-(R)-2,5-dimethyl-2-indanemethanol (Compound 1R) and ()-(S)-2,5-dimethyl-2-indanemethanol (Compound 1S)

[0105] Racemic 2,5-Dimethyl-2-indanemethanol (14.4 g) was resolved in portions of 1 g on a preparative HPLC column (Chiralpack AD; 2511 cm, 20 mm), eluting with isohexane/EtOH 95:5. After concentration to dryness, (+)-(S)-2,5-Dimethyl-2-indanemethanol (6.39 g) and ()-(R)-2,5-Dimethyl-2-indanemethanol (6.15 g) were obtained and further purified by flash chromatography and bulb-to-bulb distillation (boiling at 1108 oven temp./0.01 mbar). The(S)- and (R)-isomers of 2,5-Dimethyl-2-indanemethanol were >99% and >98%. The absolute configuration of (+)-(S)-2,5-dimethyl-2-indanemethanol was established through X-ray diffraction, using crystals of the ester obtained from the condensation of it with ()-camphanoyl chloride (see Helv. Chim. Acta 2005, 88, 3109).

2-(Methoxymethyl)-2,5-dimethyl-2,3-dihydro-1H-indene (Compound 2)

[0106] The synthesis of 2-(methoxymethyl)-2,5-dimethyl-2,3-dihydro-1H-indene was accomplished in one step starting from 2,5-dimethyl-2-indanemethanol.

[0107] NaH (55% suspension in mineral oil, 0.34 g, 7.7 mmol, 1.4 eq) was washed with pentane (3 times) and suspended in THF (5.0 mL). A solution of 2,5-dimethyl-2-indanemethanol (1.0 g, 5.5 mmol, 1.0 eq) in THF (10 mL) was added dropwise and the mixture was stirred at room temperature during 0.5 hours. MeI (0.59 mL, 9.4 mmol, 1.7 eq) was added dropwise and the mixture was stirred at room temperature for 16 hours. The mixture was then diluted with Et.sub.2O and the reaction was quenched through cautious addition of water. The organic layer was washed with sat. aqueous NaHCO.sub.3 and brine, dried over MgSO.sub.4, filtered and concentrated in vacuo to afford a yellow crude oil. The latter was purified by bulb-to-bulb distillation (0.30 mbar, oven temp. 75 C.) to furnish the product as a clear colorless oil (1.03 g, 5.42 mmol, 96% yield, 98% purity).

[0108] Analytical data:

[0109] .sup.1H-NMR: 7.04 (d, J=7.56 Hz, 1 H, Ar), 6.98 (s, 1 H, Ar), 6.93 (d, J=7.44 Hz, 1 H, Ar), 3.34 (s, 3 H, OCH.sub.3), 3.24 (s, 2 H, CH.sub.2OMe), 2.89 (d, J=9.01 Hz, 1 H, ArCH.sub.2), 2.86 (d, J=8.76 Hz, 1 H, ArCH.sub.2), 2.61 (d, J=3.66 Hz, 1 H, ArCH.sub.2), 2.58 (d, J=3.54 Hz, 1 H, ArCH.sub.2), 2.30 (s, 3 H, ArCH.sub.3), 1.16 (s, 3 H, aliphat. CH.sub.3).

[0110] .sup.13C-NMR: 142.8, 139.6, 135.7, 126.9, 125.5, 124.5, 80.8, 59.3, 44.1, 43.2, 42.9, 24.7, 21.2.

1-(2,5-Dimethyl-2,3-dihydro-1H-inden-2-yl)ethan-1-one (Compound 6)

[0111] The synthesis of 1-(2,5-dimethyl-2,3-dihydro-1H-inden-2-yl)ethan-1-one was accomplished in two steps starting from 2,5-dimethyl-2,3-dihydro-1H-indene-2-carbaldehyde. The latter was prepared according to the procedure reported in the publication Helv. Chim. Acta 2005, 88, 3118.

[0112] A solution of 2,5-dimethyl-2,3-dihydro-1H-indene-2-carbaldehyde (10.2 g, 58.8 mmol, 1.0 eq) in Et.sub.2O (60 mL) was added dropwise to a suspension of MeMgBr (3.0 M in Et.sub.2O, 31.4 mL, 94.0 mmol, 1.6 eq) in Et.sub.2O (25 mL) under stirring at room temperature over a period of 1 hour. Exothermy was observed during the addition (22 to 34 C.). The resulting mixture was stirred at room temperature for 1 hour. The reaction was quenched by pouring the mixture onto ice/sat. aqueous NH.sub.4Cl. The aqueous layer was extracted with EtOAc (3 times). The combined organic layers were washed with brine (once), dried over MgSO.sub.4, filtered and the solvent was removed under reduced pressure to afford a pale yellow crude oil. The latter was purified by bulb-to-bulb distillation (0.14 mbar, oven temp.: 150 C.) to furnish 1-(2,5-dimethyl-2,3-dihydro-1H-inden-2-yl)ethan-1-ol as a colorless oil (10.0 g, 52.6 mmol, yield 89%; 1:1 mixture of diastereoisomers).

[0113] Analytical data:

[0114] .sup.1H-NMR: 7.04 (dd, J=3.98, 7.51 Hz, 1 H, Ar), 6.98 (d, J=4.07 Hz, 1 H, Ar), 6.93 (d, J=7.63 Hz, 1 H, Ar), 3.77 (q, J=6.35 Hz, 1 H, CHOH), 3.01-2.85 (m, 2 H, ArCH.sub.2), 2.60 (d, J=15.74 Hz, 1 H, ArCH.sub.2), 2.47 (d, J=15.70 Hz, 1 H, ArCH.sub.2), 2.30 (s, 3 H, ArCH.sub.3), 1.61 (broad s, 1 H, OH), 1.18 (d, J=6.34 Hz, 3 H, CHCH.sub.3), 1.04 (s, 3 H, aliphat. CH.sub.3).

[0115] .sup.13C-NMR (the signals corresponding to the two diastereoisomers are partially resolved): 142.7, 142.6, 139.5, 139.4, 135.7, 127.0, 125.6, 125.4, 124.6, 124.4, 74.4, 48.2, 43.4, 43.1, 43.0, 42.9, 21.4, 21.4, 21.2, 18.9.

[0116] 1-(2,5-Dimethyl-2,3-dihydro-1H-inden-2-yl)ethan-1-ol (10.0 g, 52.6 mmol, 1.0 eq) obtained from the previous reaction was dissolved in acetone (50 mL) and the resulting clear solution was cooled to 0 C. (ice/water bath) under stirring. Jones reagent (2.7 M, 21.4 mL, 57.8 mmol, 1.1 eq) was added dropwise, at such a rate to maintain the temperature under 5 C. The reaction mixture was then stirred at room temperature for 1 additional hour. The reaction was quenched by pouring the mixture onto brine. The aqueous layer was extracted with Et.sub.2O (3 times). The combined organic layers were washed with brine (3 times), sat. aqueous NaHCO.sub.3 (once) and again with brine, dried over MgSO.sub.4, filtered and concentrated in vacuo, to afford a yellow crude oil. The latter was purified by bulb-to-bulb distillation (0.12 mbar, oven temp. 120 C.) to furnish the product as a clear colorless solid (8.40 g, 43.8 mmol, 83% yield, 98% purity).

[0117] Analytical data:

[0118] .sup.1H-NMR: 7.07 (d, J=7.60 Hz, 1 H, Ar), 7.01 (s, 1 H, Ar), 6.97 (d, J=7.65 Hz, 1 H, Ar), 3.36 (d, J=10.45 Hz, 1 H, ArCH.sub.2), 3.33 (d, J=10.30 Hz, 1 H, ArCH.sub.2), 2.74 (d, J=4.05 Hz, 1 H, ArCH.sub.2), 2.70 (d, J=4.20 Hz, 1 H, ArCH.sub.2), 2.31 (s, 3 H, COCH.sub.3), 2.20 (s, 3 H, ArCH.sub.3), 1.30 (s, 3 H, aliphat. CH.sub.3).

[0119] .sup.13C-NMR: 212.0, 141.3, 138.0, 136.3, 127.4, 125.5, 124.5, 56.2, 42.6, 42.3, 25.6, 24.6, 21.2.

(2,6-dimethyl-1,2,3,4-tetrahydro-2-naphthalenyl)methanol (Compound 7)

[0120] The synthesis of (2,6-dimethyl-1,2,3,4-tetrahydronaphthalen-2-yl)methanol was accomplished in five steps starting from p-xylene and maleic anhydride.

[0121] Maleic aldehyde (22.0 g, 224 mmol, 1.00 equivalent) was dissolved in p-xylene (279.0 mL, 2244 mmol, 10.0 eq). Di-tert-butyl peroxide (0.234 g, 1.57 mmol, 0.007 eq) was added to the resulting solution under stirring and the mixture was heated to 150 C. (bath temperature) during 5 hours. The excess p-xylene was removed by distillation under reduced pressure. The residue was purified by crystallization from a mixture of EtOAc (30 mL) and heptane (30 mL) to give the pure product as an off-white solid (21.8 g). An additional amount (8.30 g) of the pure product was obtained through bulb-to-bulb distillation of the mother liquor (0.16 mbar, over temp. 225 C.) (Total amount of the product: 73.6 g, 147 mmol, 74% yield, 99% purity).

[0122] .sup.1H-NMR: 7.14 (d, J=7.88, 2H), 7.05 (d, J=8.00 Hz, 2H), 3.42 (m, J=2.11, 1H), 3.17 (dd, J=4.92, 14.27, 1H), 2.98 (dd, J=8.28, 14.04, 1H), 2.93 (dd, J=9.78, 18.91, 1H), 2.71 (dd, J=6.46, 18.99, 1H), 2.33 (s, 3H).

[0123] Methanesulfonic acid (100 g, 102 mmol, 11.0 eq) was added to the anhydride obtained from the previous reaction (3-(4-methylbenzyl)dihydrofuran-2,5-dione, 19 g, 93 mmol, 1.0 eq). The resulting mixture was then stirred and heated to 100 C., gradually transforming into a suspension. The mixture was cooled to 15 C. using a water bath. MeOH (70 mL) was added dropwise, while maintaining the temperature under 20 C. Once the addition was completed, the mixture was stirred at room temperature for another 15 minutes and then partitioned between brine and Et.sub.2O. The aqueous layer was extracted with Et.sub.2O (4 times). The combined organic layers were washed with brine (5 times), dried over MgSO.sub.4, filtered and concentrated in vacuo to afford a red-brown crude oil. Bulb-to-bulb distillation (twice, 0.18 mbar, oven temp. 190-210 C.) furnished the pure ketoester as a pale yellow solid (13.6 g, 62.5 mmol, 67% yield).

[0124] .sup.1H-NMR: 7.83 (s, 1H), 7.32 (dd, J=1.55, 8.05, 1H), 7.17 (d, J=7.80, 1H), 3.72 (3H, s), 3.22-3.14 (m, 3H), 2.92 (m, J=5.23, 1H), 2.80 (m, J=5.57, 1H), 2.36 (s, 3H).

[0125] The ketoester obtained from the previous reaction (methyl 6-methyl-4-oxo-1,2,3,4-tetrahydronaphthalene-2-carboxylate, 13.0 g, 59.6 mmol) was dissolved in AcOH (130 mL). Palladium on charcoal (10%, 1.2 g) was added and the resulting suspension was shaken under an atmosphere of H.sub.2 (1 atm) during 2 days. After this time, the reaction mixture was filtered through celite, which was then washed with Et.sub.2O. The filtrate was concentrated in vacuo to furnish a pale yellow crude oil. Bulb-to-bulb distillation (0.15 mbar, oven tem. 130 C.) afforded the pure ester (10.5 g, 51.6 mmol, 86% yield).

[0126] .sup.1H-NMR: 6.98 (d, J=7.76, 1H), 6.92 (d, J=7.96, 1H), 6.90 (s, 1H), 3.71 (s, 3 H), 2.99-2.90 (m, 2H), 2.86-2.76 (m, 2H), 2.71 (m, J=3.04, 1H), 2.28 (s, 3H), 2.19 (m, J=4.11, 1H), 1.83 (m, J=3.74, 1H).

[0127] Under a nitrogen atmosphere, the ester obtained from the previous reaction (methyl 6-methyl-1,2,3,4-tetrahydronaphthalene-2-carboxylate, 10.5 g, 51.6 mmol, 1.0 eq) was dissolved in THF (70 mL) and the resulting solution was cooled to 78 C. After 10 minutes, an LDA solution (2.0 M in THF, 33.5 mL, 67.0 mmol, 1.3 eq) was added dropwise, while maintaining the temperature under 68 C. The resulting suspension was subsequently stirred at 78 C. for 2 hours. MeI (4.2 mL, 67 mmol, 1.3 eq) was then added dropwise and the mixture was further stirred for 2 hours, while allowing the temperature to rise up to 55 C. The reaction was quenched by addition of sat. aqueous NH.sub.4Cl. The aqueous layer was extracted with Et.sub.2O (3 times). The combined organic layers were washed once with brine, dried over MgSO.sub.4, filtered and concentrated in vacuo to furnish a pale yellow crude oil. Purification by column chromatography (SiO.sub.2, elution with cyclohexane/EtOAC 24/1 to 10/1) afforded the pure product as a pale yellow solid (7.38 g, 33.4 mmol, 67% yield).

[0128] .sup.1H-NMR: 6.97 (d, J=7.70, 1H), 6.91 (d, J=7.85, 1H), 6.89 (s, 1H), 3.65 (s, 3H), 3.19 (d, J=16.30, 1H), 2.78 (t, J=6.35, 1H), 2.61 (d, J=16.30, 1H), 2.27 (s, 3H), 2.13 (m, J=3.05, 1H), 1.76 (m, J=6.74, 1H), 1.26 (s, 3H).

[0129] LiAlH.sub.4 (1.50 g, 39.6 mmol, 1.3 eq) was suspended in Et.sub.2O (60 mL). The suspension was cooled under stirring to 0 C. A solution of the ester obtained from the previous reaction (methyl 2,6-dimethyl-1,2,3,4-tetrahydronaphthalene-2-carboxylate, 6.60 g, 30.2 mmol, 1.0 eq) was then added dropwise during 1 hour. The reaction mixture was stirred at room temperature for 1 additional hour and then cooled back to 0 C. Water (1.5 mL), aqueous NaOH (15% w/w, 1.5 mL), and water (4.5 mL) were carefully added in this order under vigorous stirring. The resulting suspension was further stirred at room temperature for 45 minutes. The solids were filtered off through celite and washed with Et.sub.2O (5 times). The organic solution was concentrated in vacuo to afford a pale yellow crude oil, which was purified by bulb-to bulb distillation (0.15 mbar, oven temp. 130 C.). The pure product (4.45 g, 23.4 mmol, 77% yield, 99% purity) was obtained as a colorless oil.

[0130] .sup.1H-NMR: 6.96-6.88 (m, 3 H), 3.44 (d, J=10.68, 1H), 3.40 (d, J=10.64, 1 H), 2.76 (d, J=6.44, 1H), 2.74 (d, J=6.44, 1 H), 2.62 (d, J=16.33, 1 H), 2.43 (d, J=16.29, 1 H), 2.28 (s, 3 H), 1.72-1.61 (m, 2H), 1.54 (m, J=4.25, 1H), 0.97 (s, 3H).

[0131] .sup.13C-NMR: 135.6, 135.0, 132.3, 129.4, 129.3, 126.5, 71.3, 37.9, 34.5, 30.8, 25.8, 22.1, 20.9.

(2,4,5-trimethyl-2,3-dihydro-1H-inden-2-yl)methanol (Compound 2)

[0132] The synthesis of (2,4,5-Trimethyl-2-indanemethanol was accomplished in six steps starting from 2,3-dimethylbenzaldehyde.

[0133] Ethyl 2-(diethoxyphosphoryl)propanoate (80.0 g, 335 mmol, 1.5 eq) was added to a stirred solution of 2,3-dimethylbenzaldehyde (30.0 g, 224 mmol, 1.0 eq) in pentane (300 mL) at room temperature. A solution of NaOEt (21% w/w in EtOH, 109 mL, 293 mmol, 1.3 eq) was subsequently added dropwise under stirring, while cooling the reaction mixture with a water bath. Once the addition was completed, the resulting mixture was stirred at reflux for 45 minutes. The reaction mixture was then cooled to 0 C. and quenched by addition of aqueous NaOH (1 N, 300 mL). The organic layer was separated and washed again with NaOH (1 N, 300 mL). The combined aqueous layers were extracted with Et.sub.2O (3), washed with sat. aqueous NaHCO.sub.3, brine (twice), dried over MgSO.sub.4, filtered and concentrated in vacuo to afford an orange crude oil. Bulb-to bulb distillation (0.15 mbar, oven temp. 150-155 C.) afforded the product as a colorless oil (46.5 g, 213 mmol, 95% yield; 94:6 mixture of E-Z isomers).

[0134] .sup.1H-NMR (major diastereoisomer): 7.79 (s, 1 H), 7.13-7.06 (m, 2 H), 7.01 (m, J=3.00, m), 4.28 (q, J=7.13, 2 H), 2.29 (s, 3 H), 2.17 (s, 3 H), 1.90 (d, J=1.40, 3 H), 1.35 (t, J=7.13, 3 H).

[0135] To a solution of the esters obtained in the previous reaction (ethyl 3-(2,3-dimethylphenyl)-2-methylacrylate, 46.5 g, 213 mmol) in EtOAc (50 mL) was added palladium on charcoal (10%, 1.2 g) and the resulting suspension was stirred under H.sub.2 (40 atm) in an autoclave. The solids were then filtered off through celite and washed with CH.sub.2Cl.sub.2 (5 times). Removal of the solvent under reduced pressure afforded the crude product as a colorless oil (46.5 g).

[0136] The latter was then dissolved in a 2.5 N NaOH solution in water/EtOH. The resulting mixture was heated to reflux. The mixture was cooled down to 0 C. with an ice/water-bath. Under stirring, concentrated aqueous HCl was added in small portions until acidic pH (pH 1). The aqueous layer was extracted CH.sub.2Cl.sub.2 (4 times). The combined organic layers were washed with brine, dried over MgSO.sub.4, filtered and concentrated in vacuo to afford an oil (38.1 g), which was not submitted to further purification. Finally, the so prepared carboxylic acid was added to polyphosphoric acid (PPA, 300 g), preheated to 100 C. The resulting mixture rapidly converted into a suspension, which was stirred at 110 C. for 1 hour. The reaction was then quenched by pouring the mixture onto ice/water, with formation of a red solution. The aqueous layer was extracted with Et.sub.2O (4 times). The combined organic layers were washed once with brine, dried over MgSO.sub.4, filtered and the concentrated in vacuo to afford a red-brown crude oil. Bulb-to-bulb distillation (0.15 mbar, oven temp. 140-170 C.) furnished the pure product (23.0 g, 132 mmol, 62% yield over 3 steps) as a pale yellow solid.

[0137] .sup.1H-NMR: 7.50 (d, J=7.74, 1 H), 7.17 (d, J=7.74, 1 H), 3.29 (dd, J=7.74, 17.00, 1 H), 2.69 (m, J=3.77, 1 H), 2.58 (dd, J=1.85, 18.89, 1 H), 2.35 (s, 3 H), 2.23 (s, 3 H), 1.30 (d, J=7.45, 3 H).

[0138] The 2,4,5-trimethylindanone (22.2 g, 127 mmol, 1.0 eq) obtained from the previous reaction was dissolved in toluene (52 mL). K.sub.2CO.sub.3 (8.89 g, 63.7 mmol, 0.5 eq) was then added and the resulting mixture was heated to 50 C. under stirring. A solution of formaldehyde in MeOH (Formacel, 55% w/w, 10.5 mL, 204 mmol, 1.6 eq) was added dropwise and the reaction mixture was then stirred at 50 C. for 3 hours. The reaction was subsequently stopped and allowed to cool down to room temperature. The mixture was diluted with Et.sub.2O and washed brine (3 times), dried over MgSO.sub.4, filtered and concentrated in vacuo. Purification by column chromatography (SiO.sub.2, elution with CH.sub.2Cl.sub.2) afforded the pure product (22.7 g, 111 mmol, 82%) as a colorless solid.

[0139] .sup.1H-NMR: 7.47 (d, J=7.78, 1H), 7.16 (d, J=7.78, 1H), 3.81 (d, J=10.70, 1 H), 3.61 (d, J=10.70, 1H), 3.14 (d, J=17.11, 1H), 2.77 (d, J=17.14, 1H), 2.65 (broad s, 1H), 2.36 (s, 3H), 2.24 (s, 3H), 1.23 (s, 3H).

[0140] The hydroxyketone obtained from the previous reaction (2-(hydroxymethyl)-2,4,5-trimethyl-2,3-dihydro-1H-inden-1-one, 22.3 g, 109 mmol) was dissolved in AcOH (440 mL). Palladium on charcoal (10%, 1.2 g) was added and the resulting suspension was shaken under an atmosphere of H.sub.2 (1 atm) during 3 days. After this time, the reaction mixture was filtered through celite, which was then washed with Et.sub.2O. The filtrate was concentrated in vacuo to furnish a pale yellow crude oil. Purification by column chromatography (SiO.sub.2, elution with cyclohexane/EtOAC 45/5 to 40/10.) afforded the pure product (12.9 g, 67.2 mmol, 62% yield, 98% purity) as a pale yellow oil. A sample was further purified by bulb-to-bulb distillation (0.16-0.17 mbar, oven temp. 140 C.) to give a colorless oil (99% purity)

[0141] .sup.1H-NMR: 6.94 (d, J=7.60, 1H), 6.90 (d, J=7.55, 1H), 3.51 (s, 2H), 2.89 (d, J=14.07, 1H), 2.86 (d, J=13.65, 1H), 2.65 (d, J=15.85, 1H), 2.60 (d, J=16.10, 1H), 2.24 (s, 3H), 2.14 (s, 3H), 1.65 (s, 1H), 1.18 (s, 3H).

[0142] .sup.13C-NMR: 141.5, 139.7, 134.1, 132.6, 128.0, 121.7, 70.9, 44.4, 42.9, 42.0, 24.4, 19.6, 15.8.

(2,5-dimethyl-2-indanyl)methyl acetate (Compound 10)

[0143] The synthesis of (2,5-dimethyl-2,3-dihydro-1H-inden-2-yl)methyl acetate was accomplished in one step starting from 2,5-dimethyl-2-indanemethanol.

[0144] A solution of 2,5-dimethyl-2-indanemethanol (0.57 g, 3.1 mmol) in pyridine (5 mL) and acetic anhydride (5 mL) was stirred at room temperature for 3 hours. The mixture was then concentrated under reduced pressure and the residue was evaporated three times from toluene to obtain a crude oil. The latter was purified through bulb-to-bulb distillation (0.35 mbar, oven temp. 100-135 C.) to furnish the product (0.63 g, 2.5 mmol, 87% yield, 94% purity) as an oil.

[0145] .sup.1H-NMR: 7.04 (d, J=7.56, 1 H) 6.98 (s, 1H), 6.94 (d, J=7.60, 1H), 3.99 (s, 2H), 2.89 (dd, J=4.16, 15.79, 2H), 2.63 (d, J=15.63, 2H), 2.30 (s, 3H), 2.05 (s, 3H), 1.16 (s, 3H).

[0146] .sup.13C-NMR: 171.2, 142.2, 139.0, 135.9, 127.1, 125.5, 124.5, 71.3, 43.3, 43.0, 42.7, 24.3, 21.2, 20.9.

2-ethyl-5-methyl-2-indanmethanol (Compound 11)

[0147] The synthesis of (2-ethyl-5-methyl-2,3-dihydro-1H-inden-2-yl)methanol was accomplished in four steps starting from 5-methylindanone.

[0148] NaH (55% dispersion in mineral oil, 3.9 g, 90 mmol, 2.2 eq) was washed with pentane (3 times) and suspended in a mixture of toluene (50 ml) and 1,2-dimethoxyethane (20 ml). Dimethyl carbonate (9.0 g, 100 mmol) was added and the mixture was heated to 60 C. A solution of 5-methylindanone (6.0 g, 41 mmol) in toluene (20 ml) was added dropwise over a period of 1 hour, while maintaining the temperature between 60-80 C. (H.sub.2 evolution). After stirring for 2 hours at 80 C., the mixture was cooled, diluted with ether and saturated aqueous NaHCO.sub.3. The organic layer was washed with brine (twice), dried over Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford an oil. Bulb-to-bulb distillation (0.2 mbar, oven temp. 175 C.) provided methyl 5-methyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate as an oil (4.92 g, 24.1 mmol, 59% yield). The product was crystallized from ether-pentane at 30 C. to afford colorless crystals (mp 42-46 C.).

[0149] .sup.1H-NMR: 7.65 (d, J=7.89, 1H), 7.29 (s, 1H), 7.20 (d, J=7.92, 1H), 3.78 (s, 3H), 3.72 (dd, J=4.02, 8.23, 1H), 3.50 (dd, J=3.96, 17.25, 1H), 3.31 (dd, J=8.25, 17.25, 1H), 2.44 (s, 3H).

[0150] .sup.13C-NMR: 199.0, 169.7, 154.1, 146.9, 133.0, 129.1, 126.9, 124.5, 53.3, 52.7, 30.1, 22.1.

[0151] To a stirred solution of methyl 5-methyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (2.0 g, 10 mmol, 1.0 eq) in THF at room temperature was added K.sub.2CO.sub.3 (2.8 g, 20 mmol, 2.0 eq) and ethyl iodide (2.34 g, 15 mmol, 1.5 eq) and the mixture was heated to reflux (65 C.) during 20 hours. The mixture was then cooled to room temperature, diluted with ether, and washed with saturated aqueous NaHCO.sub.3 and brine. The organic layer was dried over Na.sub.2SO.sub.4 and concentrated under reduced pressure to afford a yellow crude oil. Bulb-to-bulb distillation (0.2 mbar, oven temp. 150 C.) afforded methyl 2-ethyl-5-methyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate as an oil (2.20 g, 9.48 mmol, 93% yield, 98% purity). Crystallization from ether at 30 C. gave colorless crystals (mp 67-68 C.).

[0152] .sup.1H-NMR: 7.65 (d, J=7.85, 1H), 7.29 (s, 1H), 7.20 (d, J=7.81, 1H), 3.68 (s, 3H), 3.66 (d, J=19.52, 1H), 3.03 (d, J=17.39, 1H), 2.45 (s, 3H), 2.14 (m, J=7.18, 1H), 1.93 (m, J=7.21, 1H), 0.87 (t, J=7.44, 3H).

[0153] .sup.13C-NMR: 202.1, 171.8, 153.6, 146.7, 133.2, 129.0, 126.7, 124.5, 61.2, 52.6, 36.1, 27.9, 22.1, 9.0.

[0154] To a solution of methyl 2-ethyl-5-methyl-1-oxo-2,3-dihydro-1H-indene-2-carboxylate (1.6 g, 7.1 mmol) in acetic acid (20 ml) was added 10% PdC (0.2 g) and the mixture was stirred under an atmosphere of H.sub.2 (1 atm) at room temperature over a period of 110 hours. The catalyst was filtered off and the filtrate was concentrated under reduced pressure to afford a yellow crude oil. Bulb-to-bulb distillation (0.2 mbar, oven temp. 125 C.) gave methyl 2-ethyl-5-methyl-2,3-dihydro-1H-indene-2-carboxylate as a colorless oil (1.40 g, 6.41 mmol, 87% yield, 97% purity).

[0155] .sup.1H-NMR: 7.04 (d, J=7.60, 1H), 6.98 (s, 1H), 6.94 (d, J=7.71), 3.68 (s, 3H), 3.41 (dd, J=4.72, 16.13, 2H), 2.84 (d, J=16.03, 2H), 2.30 (s, 3H), 1.76 (q, J=7.43, 2H), 0.86 (t, J=7.44, 3H).

[0156] .sup.13C-NMR: 177.4, 141.5, 138.3, 136.0, 127.2, 125.1, 124.1, 55.0, 51.9, 41.6, 41.4, 31.6, 21.2, 9.9.

[0157] To a stirred suspension of LiAlH.sub.4 (220 mg, 5.8 mmol, 1.0 eq) in ether (20 ml) at room temperature was added dropwise a solution of methyl 2-ethyl-5-methyl-2,3-dihydro-1H-indene-2-carboxylate (1.30 g, 5.8 mmol, 1.0 eq) in ether (10 ml) and the mixture was stirred at room temperature during 0.5 hours. The mixture was diluted with ether, acetone (0.5 ml) was added followed by 1.0 N aqueous NaOH (1.1 ml) and the mixture was stirred at room temperature during 0.5 hours. Na.sub.2SO.sub.4 was added, the solids were filtered off and the filtrate concentrated under reduced pressure to provide an oil. Bulb-to-bulb distillation (0.2 mbar, oven temp. 140 C.) gave (2-ethyl-5-methyl-2,3-dihydro-1H-inden-2-yl)methanol as a colorless oil (1.10 g, 5.78 mmol, 98% yield, >98% purity).

[0158] .sup.1H-NMR: 7.03 (d, J=7.60, 1H), 6.97 (s, 1H), 6.92 (d, J=7.60, 1H), 3.49 (d, J=3.96, 2H), 2.76 (dd, J=4.09, 16.12, 2H), 2.68 (dd, J=2.18, 16.22, 2H), 2.29 (s, 3H), 1.68 (br s, 1H), 1.59 (q, J=7.48, 2H), 0.88 (t, J=7.49, 3H).

[0159] .sup.13C-NMR: 142.7, 139.4, 135.7, 127.0, 125.4, 124.4, 67.7, 48.1, 40.6, 40.3, 29.0, 21.2, 9.0.

(5-methoxy-2-methyl-2,3-dihydro-1H-inden-2-yl)methanol (Compound 17)

[0160] The synthesis of (5-methoxy-2-methyl-2,3-dihydro-1H-inden-2-yl)methanol was accomplished in four steps starting from 3-(4-methoxyphenyl)-2-methylpropanal. Sodium acetate (92.0 g, 1.12 mol, 0.8 eq) was added to a solution of 3-(4-methoxyphenyl)-2-methylpropanal (250 g, 1.4 mol, 1.0 eq) in toluene (575 mL). The resulting mixture was heated to 30 C. and peracetic acid (117 g, 1.54 mol, 1.1 eq) was added dropwise under stirring over a period of 3 hours. The mixture was then stirred at 30 C. for one hour. The mixture was then washed with water (twice), 5% w/w aqueous Na.sub.2SO.sub.3 (twice), and water. The resulting pale yellow crude oil was submitted to bulb-to-bulb distillation (0.1 mbar, oven temp. 130-145 C.) to afford 3-(4-methoxyphenyl)-2-methylpropanoic acid (244 g, 1.29 mol, 89% yield, 99% purity) as an oil.

[0161] .sup.1H-NMR: 11.66 (br s, 1H), 7.09 (d, J=8.60, 2H), 6.82 (d, J=8.64, 2H), 3.76 (s, 3H), 3.00 (dd, J=6.38, 13.46, 1H), 2.71 (m, J=7.06, 1H), 2.61 (dd, J=7.92, 13.44, 1H), 1.16 (d, J=6.96, 3H).

[0162] .sup.13C-NMR: 182.8, 158.2, 131.0, 129.9, 113.8, 55.2, 41.5, 38.4, 16.4.

[0163] 3-(4-Methoxyphenyl)-2-methylpropanoic acid (170 g, 875 mmol) was added dropwise to polyphosphoric acid (150 g) under stirring at 95 C. over a period of 55 minutes. The resulting red mixture was then cooled to room temperature and water (140 mL) was added. Toluene (140 mL) was added and the biphasic mixture was stirred before removing the aqueous layer. The organic layer was washed with water and saturated aqueous NaHCO.sub.3. The resulting mixture was concentrated under reduced pressure, diluted in MTBE and the organic solution was washed with 10% w/w aqueous NaOH and water (4 times). Upon removal of the volatiles under reduced pressure, the resulting crude oil was submitted to bulb-to-bulb distillation (0.1 mbar, oven temp. 90-120 C.) to afford 6-methoxy-2-methyl-2,3-dihydro-1H-inden-1-one (67.3 g, 375 mmol, 43% yield, 98% purity) as an oil.

[0164] .sup.1H-NMR: 7.32 (m, 1H), 7.18-7.15 (m, 2H), 3.82 (s, 3H), 3.31 (dd, J=7.60, 16.65, 1H), 2.72 (m, J=4.34, 1H), 2.64 (dd, J=3.72, 16.65, 1H), 1.30 (d, J=7.48, 3H).

[0165] .sup.13C-NMR: 209.4, 159.4, 146.2, 137.4, 127.2, 124.0, 105.1, 55.5, 42.8, 34.3, 16.3.

[0166] 6-Methoxy-2-methyl-2,3-dihydro-1H-inden-1-one (74.5 g, 383 mmol, 1.0 eq) was dissolved in toluene (170 mL) and K.sub.2CO.sub.3 (26.5 g, 190 mmol, 0.5 eq) was added to the resulting solution. The latter was heated to 60 C. and formaldehyde (55% w/w solution in MeOH, 20.9 g, 380 mmol, 1.0 eq) was then added dropwise over a period of 90 minutes. The mixture was stirred at the same temperature for additional 60 minutes and it was then allowed to cool down to room temperature. The organic mixture was washed with water, 1% w/w aqueous H.sub.2SO.sub.4 (twice), water (3 times) and concentrated under reduced pressure. Upon crystallization from toluene, 2-(hydroxymethyl)-6-methoxy-2-methyl-2,3-dihydro-1H-inden-1-one (75.6 g, 206 mmol, 96% yield, >99% purity) was obtained.

[0167] .sup.1H-NMR: 7.33 (d, J=8.44, 1H), 7.18 (dd, J=2.56, 8.32, 1H), 7.10 (d, J=2.52, 1 H), 3.83 (dd, J=6.74, 10.70, 1H), 3.78 (s, 3H), 3.59 (dd, J=5.08, 10.72, 1H), 3.20 (d, J=16.85, 1H), 2.88 (dd, J=5.26, 6.58, 1H), 2.79 (d, J=16.81, 1H), 1.21 (s, 3H).

[0168] .sup.13C-NMR: 211.1, 159.4, 146.3, 136.9, 127.3, 124.6, 105.2, 67.8, 55.5, 51.9, 37.2, 20.7.

[0169] To a solution of 2-(hydroxymethyl)-6-methoxy-2-methyl-2,3-dihydro-1H-inden-1-one (17 g, 81 mmol) in EtOH (95 ml) was added 5% PdC (1.66 g) and the mixture was stirred under an atmosphere of H.sub.2 (1 atm) at 60 C. over a period of 70 hours. The catalyst was filtered off and the filtrate was concentrated under reduced pressure. The resulting crude product was recrystallized from petroleum ether (60-80)/toluene (3/1) to provide (5-methoxy-2-methyl-2,3-dihydro-1H-inden-2-yl)methanol (7.3 g, 37 mmol, 46% yield).

[0170] .sup.1H-NMR: 7.04 (d, J=8.12, 1H), 6.71 (m, 1H), 6.67 (dd, J=2.40, 8.16, 1H), 3.75 (s, 3H), 3.48 (s, 2H), 2.84 (dd, J=15.79, 20.67, 2H), 2.58 (dd, J=15.38, 15.3, 2H), 2.08 (s, 1H), 1.15 (s, 3H).

[0171] .sup.13C-NMR (100 MHz, CDCl.sub.3) 158.6, 144.0, 134.5, 125.2, 112.1, 110.3, 70.5, 55.3, 45.4, 42.9, 41.9, 24.0.

Example 2

Nose Receptor Based Screening Methods and Results

[0172] Identification of malodor-sensitive olfactory neurons was performed as previously described in WO 2014/210582. Identification of antagonist compounds that inhibit the response of malodor-sensitive olfactory neurons to the target malodor was performed according to Kajiya et al (2001) (K. Kajiya, et al in The Journal of Neuroscience, (2001) 21, 6018-6025).

Experiment 1: Identification of Indole Olfactory Receptor Antagonists Compound 1, Compound 2, and Compound 3

[0173] Ca.sup.2+ imaging traces of individual olfactory sensory neurons and their inhibition to Compound 1, Compound 2 or Compound 3 (MOC) are shown in FIG. 1 plots (A, C, E). Inhibition of the population of indole-response olfactory sensory neurons is shown in FIG. 1 plots (B, D, F).

[0174] Olfactory sensory neurons were stimulated with 25 M indole (MO) and 125 M MOC either alone or as a binary mixture. By comparing the peak value of the calcium-induced fluorescence ratio change induced by exposure to the target MO compound to that of the mixture of MO+MOC candidate, a modulation value was calculated. The larger the difference between the two peak values, the greater the magnitude of the modulation value. If the peak value for the MO was larger than that of the MO+MOC, the modulation value was negative, whilst the inverse produced positive modulation values. A modulation value was calculated for each cell responding to the positive-control stimulus forskolin (Pos) and the MO compound, but not to the negative-control buffer stimulus (Neg). For each candidate MOC compound, a baseline modulation value was obtained by repeated stimulations of olfactory neurons with indole alone (left box plot in B, D, F). The percentage of target malodor-responsive cells with negative modulation values less than 10% was plotted on a bar chart. Population data are represented as box plots, where the interquartile range (25-75.sup.th percentiles) of olfactory sensory neuron modulation is contained within the box, with the median indicated by the black bar and the 95.sup.th percentile by the arms.

Experiment 2: Identification of Antagonists of Feces Malodors Compounds Using Olfactory Receptors

TABLE-US-00002 TABLE 1 Summary of the results obtained on the screening of antagonist compounds for indole, skatole and dimethyl trisulfide (DMTS): Proportion.sup.3) of Proportion.sup.3) of Proportion.sup.3) of MOC Compound Indole OSNs.sup.2) Skatole OSNs.sup.2) DTMS OSNs.sup.2) 17 23% 16 14% 15 17% 14 20% 13 54% 12 57% 11 35% 10 42% 9 78% 8 30% 7 54% 6 69% 92% 94% 5 77% 87% 82% 4 41% 3 41% 2 43% 1 56% 82% 69% .sup.1)missing data mean the compound was not tested against the target malodor .sup.2)OSN means Olfactory Sensory Neurons .sup.3)the percentage of the Malodor-responsive olfactory neuron population that was inhibited by more than 10% (i.e. with modulation values less than 10%) was plotted.

[0175] Olfactory sensory neurons were stimulated with 25 M indole malodor and 125 M candidate MOC compound as a binary mixture.

[0176] Olfactory sensory neurons were stimulated with 50 M skatole malodor and 250 M candidate MOC compound as a binary mixture.

[0177] Olfactory sensory neurons were stimulated with 50 M DMTS malodor and 250 M candidate MOC compound as a binary mixture.

Example 3

Olfactometry Based Screening Methods and Results

[0178] Air dilution olfactometry was used to measure all psychophysical data of individual and mixed odorants. Odorized flows of air with precisely set concentrations were prepared by the evaporation of a known flux of odorant in a determined flow of air. The flux of odorant was delivered through a microsyringe operated by a calibrated micromotor into a heated vessel under a steady nitrogen flow. The odorant was vaporized and swept away by the nitrogen, and this primary flow was later diluted with humidified air to the desired concentration. Odorants can be presented one by one in olfactometers (see as a reference Multidimensional visualization of physical and perceptual data leading to a creative approach in fragrance development, C. Vuilleumier, M. van de Waal, H. Fontannaz, I. Cayeux and P. A. Rebetez, in Perfumer & Flavourist, 33, 55 (2008)); alternatively, a machine blending up to 12 flows of odorants in variable and adjustable proportions could be used. A sniffing outlet delivered a continuous and adjustable odorized air flow. The upper working limit was determined by the vapor pressure of the odorants at room temperature. The odorized flow was delivered at a temperature of 26 C., close to the temperature within the nose. The combination of air (540 l/h) and nitrogen (60 l/h) represented a total gas flow of 600 l/h with a relative humidity of 50%. The speed of injection of the solutions in the evaporation chamber was modulated and controlled for each subject and adjusted to obtain a medium perceived intensity (see above reference, for instance FIG. 4).

[0179] Standardized psychophysical procedures were used to determine olfactory detection thresholds (triangle testing) or perceived intensity, after a training period (see above reference).

[0180] A method was designed as an iterative process to obtain dose-response relationship and odor detection threshold of perfumery ingredients or malodorants with a minimum number of experiments (see FIG. 5 in the above reference).

[0181] FIG. 2 reports the radar plot of indole alone and indole+compound 1 obtained with a panel of 13 persons using a sensory protocol to evaluate the potential antagonists versus indole. The protocol involves two steps: [0182] Step 1: the participants evaluated the tested ingredients and indole independently to adjust their individualized concentrations by changing the rate of injection (see above description and reference) to elicit a medium intensity perception for each chemical. These concentrations, corresponding to iso-intense levels, were applied in the second step of the process. The range of concentrations to be submitted to subjects was determined from dose-response relationships for the selected ingredients and indole. In the present experiment the molar ratio Compound 1/indole varied according to the individuals from about 1/1 to 10/1 (typical preferred individual range is between 2.5/1 and 4.5/1). [0183] Step 2: Blind sensory evaluations were set; no information was disclosed to the participants on the submitted odorous stimuli. The subjects had to evaluate first indole alone at its individualized concentration and rate the following three descriptors on a linear labeled scale: [0184] Pleasantness (From Very unpleasant to Very pleasant) [0185] Freshness (From No Freshness to Very fresh) [0186] Malodor character: Animal/Fecal/Tar (From No . . . to Very . . . )

[0187] The next submission, 30 seconds after the previous one to avoid odor adaptation, involved the simultaneous injection of indole and of the tested ingredient at individualized concentrations. The same descriptors were rated.

[0188] By applying the same method to various compounds were obtained the results reported in Table 2 herein below.

TABLE-US-00003 TABLE 2 Sensory results of Indole vs (Indole + invention's Compound) Animal/Fecal/Tar Freshness Pleasantness Compound/ Compound score Reduction .sup.2) score score Indole .sup.1) Indole 6.9 0.2 0 2.2 0.2 2.6 0.2 alone 2 3.5 1.5 50 4.7 1.3 3.9 0.8 23.9 3 3.1 1.3 55 5.2 1.5 6.0 1.4 26.5 5 2.7 1.0 61 5.2 1.2 5.7 1.1 51.1 16 2.6 1.4 62 6.2 1.6 6.4 1.3 4.9 6 2.2 1.2 68 5.2 1.6 5.8 1.4 10.7 4 2.1 1.1 70 6.6 1.5 7.2 1.2 12.1 1 1.3 0.5 81 6.7 0.9 7.8 0.7 3.0 .sup.1) Median of individual molar concentrations ratios (Compound/Indole) .sup.2) In percentage

[0189] The best performers can be defined as being the one providing the highest reduction of the Animal/Fecal/Tar character when tested at the iso-intense levels.

[0190] Alternatively the best performer can be defined as being the one providing the lowest molar ratio vs. indole when tested at the iso-intense levels.