COMPOUNDS

Abstract

A compound of the formula (I)

##STR00001##

in which, independently, R.sub.1 is selected from H and methyl; R.sub.2 is selected from H, and methyl; R.sub.3 is selected from H, methyl and ethyl; R.sub.4 is selected from H, methyl and ethyl; or R.sub.3 and R.sub.4 together form a ring in which n is 1 or 2.

The compounds have the characteristic desirable odour qualities of the Damascone molecules, but lack their disadvantageous skin sensitization effects.

Claims

1. A compound of the formula (I) ##STR00005## in which, independently, R.sub.1 is selected from H and methyl; R.sub.2 is selected from H, and methyl; R.sub.3 is selected from H, methyl and ethyl; R.sub.4 is selected from H, methyl and ethyl; or R.sub.3 and R4 together form a ring in which n is 1 or 2.

2. The compound according to claim 1, wherein both R.sup.1 and R.sup.2 are hydrogen.

3. The compound according to claim 2, wherein R.sup.4 is selected from methyl and ethyl, or wherein R.sup.3 and R.sup.4 together form a cyclopentyl ring (n=1).

4. The compound according to claim 3 selected from the group consisting of (2E,1R*,2S*)-2-methyl-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one, (2E,1R*,2R*)-2-methyl-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one, (2E,6R*,7S*)-2-methyl-1-(7-methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one, (2E,6R*,7R*)-2-methyl-1-(7-methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one, (2E)-1-(2,6-dimethylcyclohex-3-en-1-yl)-2-methylbut-2-en-1-one, (2E)-1-(6-ethyl-2-methylcyclohex-3-en-1-yl)-2-methylbut-2-en-1-one, (2E)-2-methyl-1-(1,2,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one, (2E,1R*,2S*)-2-methyl-1-(2-methylcyclohex-3-en-1-yl)but-2-en-1-one, and (2E,1R*,2R*)-2-methyl-1-(2-methylcyclohex-3-en-1-yl)but-2-en-1-one.

5. (2E,1R*,2S*)-2-methyl-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one.

6. A method comprising using in a fragrance composition or incorporating in a fragrance application as a fragrance ingredient, a compound or compounds of formula (I) according to claim 1.

7. A fragrance composition comprising a compound according to claim 1 and at least one other fragrance ingredient.

8. A perfumed product comprising a perfumed product base and at least one compound according to claim 1.

9. The perfumed product according to claim 8, selected from fine perfumery, fabric care, household products, beauty and personal care products and air care products.

10. A precursor capable of generating a compound according to Formula (I) as defined in claim 1, having the Formula (II): ##STR00006## in which X is selected from SR.sup.5, NHR.sup.6 and NR.sup.6R.sup.7; R.sup.5, R.sup.6 and R.sup.7 being selected from linear or branched C.sub.1-C.sub.15 alkyl, a C.sub.3-C.sub.8 cycloalkyl or an aryl substituent, both optionally substituted with linear or branched C.sub.1-C.sub.7 alkyl groups or, in the case of NR.sup.6R.sup.7, R.sup.6 and R.sup.7, together with the nitrogen atom to which they are attached, form part of a polymeric entity;

11. A method of providing in a fragrance application a compound of Formula (I) according to claim 1, comprising (i) preparing a precursor compound according to Formula II ##STR00007## in which X is selected from SR.sup.5, NHR.sup.6 and NR.sup.6R.sup.7; R.sup.5, R.sup.6 and R.sup.7 being selected from linear or branched C.sub.1-C.sub.15 alkyl, a C.sub.3-C.sub.8 cycloalkyl or an aryl substituent, both optionally substituted with linear or branched C.sub.1C.sub.7 alkyl groups or, in the case of NR.sup.6R.sup.7, R.sup.6 and R.sup.7, together with the nitrogen atom to which they are attached, form part of a polymeric entity; (ii) adding the precursor compound of Formula II to an application; and (iii) subjecting the application to conditions that will result in the generation of a compound according to Formula (I).

12. A method comprising adding in a fragrance application, a compound according to Formula II ##STR00008## in which X is selected from SR.sup.5, NHR.sup.6 and NR.sup.6R.sup.7; R.sup.5, R.sup.6 and R.sup.7 being selected from linear or branched C.sub.1-C.sub.15 alkyl, a C.sub.3C.sub.8 cycloalkyl or an aryl substituent, both optionally substituted with linear or branched C.sub.1-C.sub.7 alkyl groups or, in the case of NR.sup.6R.sup.7, R.sup.6 and R.sup.7, together with the nitrogen atom to which they are attached, form part of a polymeric entity; for the in situ generation of a compound according to claim 1.

13. A method of providing in a fragrance application a fruity-floral fragrance note with reduced skin sensitization, comprising the addition to a fragrance application base of a compound according to claim 1.

14. The method according to claim 13, wherein both R.sup.1 and R.sup.2 are hydrogen.

15. The method according to claim 14, wherein R.sup.4 is selected from methyl and ethyl, or wherein R.sup.3 and R.sup.4 together form a cyclopentyl ring (n=1).

16. The method according to claim 15, in which the compound is selected from the group consisting of: (2E,1R*,2S*)-2-methyl-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one, (2E,1R*,2R*)-2-methyl-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one, (2E,6R*,7S*)-2-methyl-1-(7-methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one, (2E,6R*,7R*)-2-methyl-1-(7-methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one, (2E)-1-(2,6-dimethylcyclohex-3-en-1-yl)-2-methylbut-2-en-1-one, (2E)-1-(6-ethyl-2-methylcyclohex-3-en-1-yl)-2-methylbut-2-en-1-one, (2E)-2-methyl-1-(1,2,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one, (2E,1R*,2S*)-2-methyl-1-(2-methylcyclohex-3-en-1-yl)but-2-en-1-one, and (2E,1R*,2R*)-2-methyl-1-(2-methylcyclohex-3-en-1-yl)but-2-en-1-one.

17. The method according to claim 16, in which the compound is (2E,1R*,2S*)-2-methyl-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one.

Description

EXAMPLE 1

(2E,1R*,2S*)-2-Methyl-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one

[0047] In a reaction flask, an LDA solution was prepared at 70 C. under N.sub.2 atmosphere by dropwise addition of a 2.5 M solution of nBuLi in hexanes (35.8 mL, 90 mmol) to a stirred solution of iPr.sub.2NH (12.9 mL, 90 mmol) in anhydrous THF (50 mL). After stirring for 10 min at this temp., the cooling bath was removed, and the reaction mixture was allowed to warm to room temp. within 45 min. At this temp., a 0.5 M solution of 1-methyl-2-propenylmagnesium chloride in THF (244 mL, 122 mmol) was added dropwise with stirring over a period of 3 h, followed by dropwise addition of a solution of (1R*,2S*)-methyl 2,6,6-trimethylcyclohex-3-enecarboxylate (15.0 g, 81.0 mmol) in dry THF (150 mL) over a period of 1 h 30 min. The resulting reaction mixture was heated to 40 C., and stirring was continued at this temp. for 18 h. The reaction mixture was allowed to cool down to room temp., and poured into ice-cold 2 M aqueous NaOH solution (250 mL) with vigorous stirring. After stirring for 45 min., the mixture was extracted with Et.sub.2O (2300 mL), and the organic extracts were washed with water (2250 mL) and brine (1200 mL). The combined organic extracts were dried over Na.sub.2SO.sub.4, filtered, and concentrated under reduced pressure. Flash chromatography (600 g silica gel, pentane-ether, 39:1; R.sub.f=0.41) of the resulting residue afforded a 5:1 mixture of the desired (2E,1R*,2S*)-2-methyl-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one/(3Z,1R*,2S*)-1-(2,6,6-trimethylcyclohex-3-en-1-yl)pent-3-en-1-one and the starting material (11.7 g) as a yellowish liquid. Since the (3Z,1R*,2S*)-1-(2,6,6-trimethylcyclohex-3-en-1-yl)pent-3-en-1-one isomer proved to be very weak in smell, not altering the character of the main product (2E,1R*,2S*)-2-methyl-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one, only the starting material was removed by Kugelrohr distillation to afford a 5:1 mixture of (2E,1R*,2S*)-2-methyl-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one/(3Z,1R*,2S*)-1-(2,6,6-trimethylcyclohex-3-en-1-yl)pent-3-en-1-one (8.70 g,48%) as a colourless odoriferous liquid.

[0048] Spectral data for the main component (2E,1R*,2S*)-2-methyl-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one: IR (neat): 3018, 2956, 1656, 1640, 1458, 1367, 1273, 1233, 1078, 688 cm.sup.1. .sup.1H NMR (CDCl.sub.3): =0.79/0.94 (2s, 6H, CMe.sub.2-), 0.80 (d, J=7.0 Hz, 3H, CHCH.sub.3), 1.71 (m.sub.c, 1H, CMe.sub.2-CHH), 1.79 (quint, J=1.0 Hz, 3H, COCMe=CHMe), 1.85 (dq, J=7.0, 1.0 Hz, 3H, COCMe=CHMe), 1.99 (m.sub.c, 1H, CMe.sub.2-CHH), 2.27 (m.sub.c, 1H, CHCHMe-CH(CMe.sub.2)-CO), 2.94 (d, J=10.5 Hz, 1H, CHMe-CH(CMe.sub.2)-CO, trans), 5.47-5.55 (m, 2H, CHCH), 6.69 (q, J=7.0 Hz, 1H, CMe=CHMe) ppm. .sup.13C NMR (CDCl.sub.3): =11.2 (q), 14.9 (q), 20.0 (q), 20.6 (q), 29.9 (q), 31.9 (d), 33.3 (s), 42.1 (t), 54.7 (d), 124.0 (d), 132.5 (d), 136.3 (d), 141.7 (s), 205.8 (s) ppm. MS: m/z (%)=29 (9), 41 (10), 55 (35), 83 (100), 123 (8), 191 (3), 206 (5) [M.sup.+].

[0049] Odour description: fruity-floral, typical damascone, dried fruits, sweet, plum, milky, apple.

EXAMPLE 2

(2E,1R*,2R*)-2-Methyl-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one

[0050] At 30 C. under N.sub.2 atmosphere, a solution of (2E,1R*,2R*)-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one (2.00 g, 10.4 mmol) in THF (15 mL), prepared by Diels-Alder reaction of 4-methylpent-3-en-2-one and (3E)-penta-1,3-diene according to EP 1 162 190 A2 with subsequent aldol condensation with acetaldehyde according to WO 2010/080504 A1, was added over a period of 35 min. to a stirred 1.0 M solution of LiHMDS in THF (15.6 mL, 15.6 mmol). After keepin the stirred reaction mixture between 30 C. and 10 C. for 30 min, neat Mel (0.975 mL, 15.6 mmol) was added dropwise at 20 C. during a period of 20 min. After stirring at 20 C. for 10 min, the reaction mixture was allowed to warm to room temp., and the mixture was stirred for 18 h at this temp. The reaction mixture was poured into ice-cold satd. NH.sub.4Cl-solution (80 mL), and then extracted with diethyl ether (2100 mL). The combined organic extracts were washed with water (1100 mL) and brine (150 mL), and then dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure. Purification of the crude product by flash chromatography (150 g silica gel, pentane-ether, 39:1; R.sub.f=0.32) and Kugelrohr distillation afforded the title compound (2E,1R*,2R*)-2-methyl-1-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one (1.00 g, 40%) as a colourless crystals (mp: 31.5-33.5 C.).

[0051] IR (neat): 3017, 2956, 2873, 1661, 1639, 1459, 1391, 1269, 1235 1067, 1014, 653 cm.sup.1. .sup.1H NMR (CDCl.sub.3): =0.82/0.99 (2s, 6H, CMe.sub.2-), 0.86 (d, J=7.0 Hz, 3H, CHCH.sub.3), 1.57-1.71 (m, 1H, CMe.sub.2-CHH), 1.76 (s, 3H, COCMe=CHMe), 1.86 (d, J=7.0 Hz, 3H, COCMe=CHMe), 2.06-2.29 (m, 1H, CMe.sub.2-CHH), 2.53 (m.sub.c, 1H, CHCHMe-CH(CMe.sub.2)-CO), 3.28 (d, J=6.5 Hz, 1H, CHMe-CH(CMe.sub.2)-CO, cis), 5.32-5.48 (m, 1H, CHCH), 5.71 (ddt, J=10.0, 5.0, 2.5 Hz, 1H, CHCH), 6.69 (q, J=7.0 Hz, 1H, CMe=CHMe) ppm. .sup.13C NMR (CDCl.sub.3): =11.0 (q), 14.9 (q), 17.7 (q), 28.7 (q), 29.1 (q), 30.7 (d), 32.4 (s), 36.0 (t), 50.8 (d), 125.7 (d), 128.9 (d), 135.8 (d), 142.0 (s), 205.1 (s) ppm. MS: m/z (%)=29 (19), 41 (23), 55 (70), 83 (100), 123 (43), 137 (33), 151 (14), 163 (6), 177 (3), 191 (8), 206 (9) [M.sup.+].

[0052] Odour description: Minty, agrestic, fruity-floral, damascone-like.

EXAMPLE 3

(2E,6R*,7S*)-2-Methyl-1-(7-methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one and (2E,6R*,7R*)-2-Methyl-1-(7-methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one

[0053] In a reacition flask at 70 C. under N.sub.2 atmosphere, an LDA solution was prepared by dropwise addition of a 2.5 M solution of nBuLi in hexanes (9.70 mL, 24.2 mmol) to a stirred solution of iPr.sub.2NH (3.44 mL, 24.2 mmol) in anhydrous THF (15 mL). After stirring for 10 min at 70 C., the cooling bath was removed and the reaction mixture allowed to warm to room temp. within 30 min. Then, at room temp., a 0.5 M solution of 1-methyl-2-propenylmagnesium chloride in THF (66.1 mL, 33.1 mmol) was added dropwise over a period of 1 h, followed by dropwise addition during a period of 1 h of a solution of (6R*,7S*)-ethyl 7-methylspiro[4.5]dec-8-ene-6-carboxylate (5.00 g, 22.0 mmol) in dry THF (45 mL), prepared according to WO 2008151455 A1. The resulting reaction mixture was heated to 40 C., and the mixture stirred at this temp. for 18 h. The heating source was removed, and after the reaction mixture had reached room temp., it was poured into ice-cold 2 M NaOH-solution (100 mL), and stirred vigorously for 45 min. The product was extracted with diethyl ether (2200 mL), and the organic extracts were washed with water (2200 mL) and brine (1150 mL). The combined organic extracts were dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure, to provide a mixture of the crude title compounds, which were then separated and purified by flash chromatography (300 g silica gel, pentane-ether, 39:1; R.sub.f=0.67 (trans), R.sub.f=0.48 (cis)) followed by Kugelrohr distillation to provide (2E,6R*,7S*)-2-methyl-1-(7-methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one (650 mg, 12%) as a colourless liquid, and (2E,6R*,7R*)-2-methyl-1-(7-methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one (900 mg, 17%) as colorless crystals (mp: 49.2-52.0 C.).

[0054] Spectroscopic data for (2E,6R*,7S*)-2-methyl-1-(7-methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one: IR (neat): 3014, 2954, 1656, 1639, 1234, 1075, 688 cm.sup.1. .sup.1H NMR (CDCl.sub.3): =0.82 (d, J=7.0 Hz, 3H, CH.sub.3), 0.90-1.66 (m, 8H, CH.sub.2), 1.81 (quint, J=1.0 Hz, 3H, COCMe=CHMe), 1.88 (dq, J=7.0, 1.0 Hz, 3H, COCMe=CHMe), 1.89-2.07 (m, 2H, CH.sub.2), 2.64 (m.sub.c, 1H, CHCHMe-CHCO), 3.16 (d, J=10.5 Hz, 1H, CHMe-CHCO, trans), 5.49-5.59 (m, 2H, CHCH), 6.72 (qd, J=7.0, 1.0 Hz, 1H, CMe=CHMe) ppm. .sup.13 C NMR (CDCl.sub.3): =11.2 (q), 15.0 (q), 20.0 (q), 23.7 (t), 24.5 (t), 29.6 (t), 33.2 (d), 38.8 (t), 39.7 (t), 45.3 (s), 52.8 (d), 124.3 (d), 133.6 (d), 136.7 (d), 141.7 (s), 206.1 (s) ppm. MS: m/z (%)=29 (10), 41 (12), 55 (39), 83 (100), 134 (16), 149 (19), 164 (4), 217 (3), 232 (5) [M.sup.+].

[0055] Odour description for (2E,6R*,7S*)-2-methyl-1-(7-methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one: rather weak, fruity-floral, apricot, peach, slight damascone aspect.

[0056] Spectroscopic data for (2E,6R*,7R*)-2-methyl-1-(7-methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one): IR (neat): 3014, 2954, 1650, 1637, 1244, 1067, 657 cm.sup.1. .sup.1H NMR (CDCl.sub.3): =0.87 (d, J=7.5 Hz, 3H, CH.sub.3), 1.19-1.71 (m, 8H, CH.sub.2), 1.77 (quint, J=1.0 Hz, 3H, COCMe=CHMe), 1.78-1.84 (m, 1H, CH.sub.2), 1.87 (dq, J=7.0, 1.0 Hz, 3H, COMe=CHMe), 2.18-2.25 (m, 1H, CH.sub.2), 2.54 (m.sub.c, 1H, CHCHMe-CHCO) 3.32 (d, J=6.5 Hz, 1H, CHMe-CHCO, cis), 5.41-5.41 (m, 1H, HCH) 5.69-5.73 (m, 1H, CHCH), 6.68 (qd, J=7.0, 1.0 Hz, 1H, CMe=CHMe) ppm. .sup.13C NMR (CDCl.sub.3): =11.1 (q), 14.9 (q), 17.9 (q), 23.4 (t), 24.2 (t), 31.6 (d), 33.9 (t), 38.5 (t), 39.1 (t), 44.3 (s), 50.7 (d), 126.0 (d), 129.8 (d), 135.7 (d), 142.1 (s), 204.8 (s) ppm. MS: m/z (%)=29 (22), 41 (27), 55 (87), 83 (100), 134 (30), 149 (51), 164 (17), 217 (7), 232 (13) [M.sup.+].

[0057] Odour description for (2E,6R*,7R*)-2-methyl-1-(7-methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one): fresh fruity, minty, damascenone.

EXAMPLE 4

(2E)-1-(2,6-Dimethylcyclohex-3-en-1-yl)-2-methylbut-2-en-1-one as isomeric mixture

[0058] In an autoclave, a mixture of methyl crotonate (7.00 g, 68.5 mmol) and (3E)-penta-1,3-diene (9.33 g, 137 mmol) was heated to 160 C., and stirred for 65 h. Purification of the crude product by flash chromatography (500 g silica gel, pentane-ether, 39:1; R.sub.f=0.24) afforded methyl 2,6-dimethylcyclohex-3-enecarboxylate (4.20 g, 31%) as a colourless liquid. At room temp. under N.sub.2 atmosphere, a 0.5 M solution of 1-methyl-2-propenylmagnesium chloride in THF (89.0 mL, 44.6 mmol) was added dropwise over a period of 1 h 30 min to a stirred 2.0 M LDA solution in THF (16.4 mL, 32.7 mmol). Followed by dropwise addition during a period of 1 h of a solution of the above prepared 2,6-dimethylcyclohex-3-enecarboxylate (5.00 g, 29.7 mmol) in THF (50 mL). The resulting reaction mixture was heated to 40 C., and the mixture stirred at this temp. for 18 h. The heating source was removed, and after the reaction mixture had reached room temp., it was poured into ice-cold 2 M NaOH-solution (150 mL). After vigorous stirring for 45 min, the product was extracted with diethyl ether (2100 mL), and the organic extracts were washed with water (2100 mL) and brine (1100 mL). The combined organic extracts were dried over Na.sub.2SO.sub.4, filtered, and concentrated under reduced pressure. Purification of the resulting residue by flash chromatography (200 g silica gel, pentane-ether, 39:1; R.sub.f=0.27) and Kugelrohr distillation afforded the title compound (2E)-1-(2,6-dimethylcyclohex-3-en-1-yl)-2-methylbut-2-en-1-one (2.00 g, 31%) as liquid colourless mixture of isomers.

[0059] IR (neat): 3019, 2957, 1656, 1640, 1374, 1232, 1070, 684 cm.sup.1. .sup.1H NMR (CDCl.sub.3): =0.74 (d, J=6.5 Hz, 1H, CH.sub.3), 0.75 (d, J=6.5 Hz, 2H, CH.sub.3), 0.81 (d, J=7.0 Hz, 2.2H, CH.sub.3), 0.84 (d, J=6.5 Hz, 0.8H, CH.sub.3), 1.61-1.65 (m, 0.2H, cyclohexane ring), 1.67-1.77 (m, 0.8 H, cyclohexane ring), 1.77-1.80 (m, 1H, CH.sub.3), 1.82 (quint, J=1.0 Hz, 2H, CH.sub.3), 1.84-1.87 (m, 1H, CH.sub.3), 1.89 (dq, J=7.0, 1.0 Hz, 2H, CH.sub.3), 1.91-1.99 (m, 0.6H, cyclohexane ring), 1.99-2.20 (m, 1.4H, cyclohexane ring), 2.36-2.44 (m, 0.3H, cyclohexane ring), 2.45-2.56 (m, 0.7H, cyclohexane ring), 2.72 (t, J=10.0 Hz, 0.6H, cyclohexane ring), 3.13-3.28 (m, 0.4 H, cyclohexane ring), 5.49 (dq, J=10.0, 2.0 Hz, 0.6H, endocyclic-CHCH), 5.57-5.66 (m, 1.4H, endocyclic-CHCH), 6.69-6.81 (m, 1H, CHCH) ppm. .sup.13C NMR (CDCl.sub.3), two main diastereomers: =11.0 (q), 14.8 (q), 15.0 (q), 17.1 (q), 19.7 (q), 20.1 (q), 24.5 (d), 32.8 (d), 32.9 (d), 33.9 (t), 34.3 (t), 35.3 (d), 50.3 (d), 53.5 (d), 125.0 (d), 125.2 (d), 131.9 (d), 132.9 (d), 136.2 (d), 137.5 (d), 138.8 (s), 141.4 (s), 203.1 (s), 207.2 (s) ppm. MS: m/z (%)=29 (8), 39 (11), 55 (46), 83 (100), 93 (8), 108 (8), 109 (8), 135 (4), 137 (4), 177 (4), 192 (5) [M.sup.+].

[0060] Odour description: fruity-rosy, minty-agrestic, damascone-like.

EXAMPLE 5

(2E)-1-(6-Ethyl-2-methylcyclohex-3-en-1-yl)-2-methylbut-2-en-1-one as Isomeric Mixture

[0061] In an autoclave, a mixture of methyl trans-2-pentenoate (6.00 g, 52.6 mmol) and (3E)-penta-1,3-diene (7.16 g, 105 mmol) was heated with stirring to 150 C. for 48 h. Purification of the crude product by flash chromatography (500 g silica gel, pentane-ether, 39:1; R.sub.f=0.31) afforded methyl 6-ethyl-2-methylcyclohex-3-enecarboxylate (1.16 g, 12%) as a colourless liquid.

[0062] At room temp. under N.sub.2 atmosphere, a 0.5 M solution of 1-methyl-2-propenylmagnesium chloride in THF (43.5 mL, 21.7 mmol) was added dropwise over a period of 1 h to a stirred 2.0 M LDA-solution in THF (7.97 mL, 15.93 mmol). A solution of the above prepared methyl 6-ethyl-2-methylcyclohex-3-enecarboxylate (2.64 g, 14.48 mmol) in THF (30 mL) was then added dropwise over a period of 1 h. The resulting reaction mixture was heated with stirring to 40 C. for 18 h. The heating source was removed, and after the reaction mixture had reached room temp., it was poured into ice-cold 2 M NaOH-solution (150 mL). After vigorous stirring for 45 min, the product was extracted with diethyl ether (2100 mL), and the organic extracts were washed with water (2100 mL) and brine (1100 mL). The combined organic extracts were dried over Na.sub.2SO.sub.4, filtered, and concentrated under reduced pressure. Purification of the resulting residue by flash chromatography (280 g silica gel, pentane-ether, 39:1; R.sub.f=0.35) and Kugelrohr distillation afforded the title compound (2E)-1-(6-ethyl-2-methylcyclohex-3-en-1-yl)-2-methylbut-2-en-1-one (480 mg, 15%) as liquid yellowish isomeric mixture.

[0063] IR (neat): 3018, 2961, 1656, 1640, 1374, 1231, 1067, 712, 685, 644 cm.sup.1. .sup.1H NMR (CDCl.sub.3): =0.76 (d, J=7.0 Hz, 1H, CH.sub.3), 0.78-0.85 (4 d, 5H, CH.sub.3), 0.86-1.12 (m, 2H, CH.sub.2), 1.25 (ddd, J=13.0, 7.5, 3.5 Hz, 0.6H, cyclohexane ring), 1.42-1.57 (m, 0.4H, cyclohexane ring), 1.60-1.75 (m, 1H, cyclohexane ring), 1.78-1.80 (m, 1H, CH.sub.3), 1.81-1.84 (m, 2H, CH.sub.3), 1.86 (dq, J=7.0, 1.0 Hz, 1H, CH.sub.3), 1.87-1.92 (m, 2H, CH.sub.3), 2.18-2.58 (series of m, 2H, cyclohexane ring), 2.80 (t, J=10.0 Hz, 0.6H, cyclohexane ring), 3.14-3.25 (m, 0.5H, cyclohexane ring), 3.30 (dd, J=11.0, 5.5 Hz, 0.3H, cyclohexane ring), 5.49 (dq, J=10.0, 2.0 Hz, 0.6H, endocyclic-CHCH), 5.58-5.72 (m, 1.4H, endocyclic-CHCH), 6.68-6.84 (m, 1H, CHCH) ppm. .sup.13C NMR (CDCl.sub.3), two main diastereomers: =10.6 (q), 11.0 (q), 11.1 (q), 11.2 (q), 14.8 (q), 15.0 (q), 17.2 (q), 20.1 (q), 26.5 (t), 27.1 (t), 30.1 (t), 30.5 (d), 30.6 (t), 32.7 (d), 35.5 (d), 39.1 (d), 48.2 (d), 52.5 (d), 124.9 (d), 125.1 (d), 131.8 (d), 132.9 (d), 136.0 (d), 137.6 (d), 138.8 (s), 141.4 (s), 203.3 (s), 207.6 (s) ppm. MS: m/z (%)=29 (9), 41 (8), 55 (39), 83 (100), 93 (9), 122 (6), 137 (4), 177 (1), 192 (2), 206 (2, [M.sup.+].

[0064] Odour description: fruity-floral, apple, slightly aromatic, in direction of Damascone alpha.

EXAMPLE 6

(2E,1R*,2S*,6S*)-2-Methyl-1-(1,2,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one as Isomeric Mixture

[0065] In an autoclave, a mixture of ethyl tiglate (7.00 g, 53.5 mmol) and (3E)-penta-1,3-diene (8.02 g, 118 mmol) was heated with stirring to 170 C. for 72 h. Purification of the crude product by flash chromatography (600 g silica gel, pentaneether, 39:1; R.sub.f=0.33) afforded ethyl 1,2,6-trimethylcyclohex-3-enecarboxylate (1.6 g, 15%) as a colourless liquid.

[0066] In a reacition flask at 70 C. under N.sub.2 atmosphere, an LDA solution was prepared by dropwise addition of a 2.5 M solution of nBuLi in hexanes (6.66 mL, 16.6 mmol) to a stirred solution of/Fr.sub.2NH (2.34 mL, 16.6 mmol) in anhydrous THF (10 mL). After stirring for 10 min at 70 C., the cooling bath was removed, and the reaction mixture allowed to warm to room temp. within 30 min. At room temp., a 0.5 M solution of 1-methyl-2-propenylmagnesium chloride in THF (45.4 mL, 22.70 mmol) was then added dropwise with stirring over a period of 2 h, followed by dropwise addition during a period of 45 min of a solution of ethyl 1,2,6-trimethylcyclohex-3-enecarboxylate (3.00 g, 15.1 mmol) in dry THF (20 mL).

[0067] The resulting reaction mixture was heated with stirring to 40 C. for 18 h. The heating source was removed, and after the reaction mixture had reached room temp., it was poured into ice-cold 2 M NaOH-solution (100 mL). After vigorous stirring for 45 min, the product was extracted with diethyl ether (2150 mL), and the organic extracts were washed with water (2150 mL) and brine (1100 mL). The combined organic extracts were dried over Na.sub.2SO.sub.4, filtered, and concentrated under reduced pressure. Purification of the resulting residue by flash chromatography (300 g silica gel, pentaneether, 39:1; R.sub.f=0.35) and Kugelrohr distillation afforded the (2E,1R*,2S*,6S*)-configured title compound 2-methyl-1-(1,2,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one as the main component (60%) of a liquid clolourless isomeric mixture (130 mg, 4%).

[0068] IR (neat): 3020, 2962, 2931, 1702, 1659, 1451, 1374, 1249, 1035, 1007, 979, 713, 605, 541 cm.sup.1. .sup.1H NMR (C.sub.6D.sub.6), major component: =0.88 (d, J=6.5 Hz, 3H, CH.sub.3), 0.95 (d, J=7.0 Hz, 3H, CH.sub.3), 1.11 (s, 3H, CH.sub.3), 1.40 (dq, J=7.0, 1.0 Hz, 3H, CH.sub.3), 1.54 (dd, J=19.5, 11.0 Hz, 1H, CH.sub.aH.sub.b), 1.70 (quint, J=1.0 Hz, 3H, CH.sub.3), 1.93 (ddd, J=19.5, 6.0, 3.0 Hz, 1H, CH.sub.aH.sub.b), 2.17 (qt, J=7.0, 3.0 Hz, 1H, CHC.sub.3), 2.56 (dquint, J=11.0, 6.5, 6.5, 6.5, 6.5 Hz, 1H, CH.sub.2CHCH.sub.3), 5.50-5.52 (m, 2H, 2=CHCH.sub.2), 5.85 (qq, J=7.0, 1.5 Hz, 1H, CHCH.sub.3) ppm. .sup.13C NMR (C.sub.6D.sub.6), major component: =13.4 (q), 13.7 (q), 17.3 (2q), 18.8 (q), 27.3 (d), 31.9 (t), 40.4 (s), 52.2 (s), 125.0 (d), 127.1 (d), 130.5 (d), 139.3 (s), 208.2 (s). MS: m/z (%)=29 (10), 41 (13), 55 (45), 83 (100), 91 (13), 107 (20), 122 (21), 123 (69), 139 (4), 151 (3), 177 (1), 191 (2), 206 (6, [M.sup.+]).

[0069] Odour description: red fruits, raspberry, green-fruity, with a bell pepper nuance and rooty facets.

EXAMPLE 7

2E,1R*,2S*)-2-Methyl-1-(2-methylcyclohex-3-en-1-yl)but-2-en-1-one

[0070] At room temp., a solution of ethyl acrylate (80.0 g, 799 mmol) in toluene (100 mL) was added dropwise to a a stirred suspension of aluminium trichloride (15.98 g, 120 mmol) and toluene (150 mL). After the addition the reaction mixture was stirred for 20 min at room temp., followed by dropwise addition of a solution of (3E)-penta-1,3-diene (82.0 g, 1199 mmol) in toluene (100 mL). The temp. was maintained between 25 C. and 36 C. by immersion in a water bath, and stirring was then continued for further 24 h at room temp.

[0071] The reaction mixture was poured into ice-cold 2 M HCl-solution (200 mL), and the product was extracted with hexane (2200 mL). The organic extracts were washed with water (1200 mL) and brine (1200 mL), combined organic and were dried with MgSO.sub.4, filtered, and concentrated under reduced pressure. Purification of the resulting residue by thin-film distillation (120 C./0.20 mbar), followed by disillation employing a Sulzer columm under high vacuo afforded (1R*,2S*)-ethyl 2-methylcyclohex-3-enecarboxylate (46.1 g, 34%) as colorless liquid.

[0072] At 70 C. under N.sub.2 atmosphere, an LDA solution was prepared in a reacition flask by dropwise addition of a 2.5 M solution of nBuLi in hexanes (12.7 mL, 31.7 mmol) to a stirred solution of iPr.sub.2NH (4.5 mL, 31.7 mmol) in anhydrous THF (15 mL). After stirring for 10 min at 70 C., the cooling bath was removed, and the reaction mixture allowed to warm to room temp. over a period of 30 min. At room temp., a 0.5 M solution of 1-methyl-2-propenylmagnesium chloride in THF (86.0 mL, 43.2 mmol) was then added dropwise over a period of 2 h, followed by dropwise addition during a period of 1 h of a solution of (1R*,2S*-ethyl 2-methylcyclohex-3-enecarboxylate (5.00 g, 28.8 mmol) in dry THF (45 mL), as prepared above. The resulting reaction mixture was heated to 40 C., and stirred at this temp. for 18 h. The heating source was removed, and the reaction mixture, after it had reached room temp., poured into ice-cold 2 M NaOH-solution (100 mL). After stirring vigorously for 45 min., the product was extracted with diethyl ether (2200 mL), and the organic extracts were washed with water (2200 mL) and brine (1150 mL). The combined organic extracts were dried with Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure. Purification of the resulting residue by flash chromatography (300 g silica gel, pentane-ether, 39:1; R.sub.f=0.19) and Kugelrohr distillation afforded the title compound (2E,1R*,2S*)-2-Methyl-1-(2-methylcyclohex-3-en-1-yl)but-2-en-1-one (1.00 g, 17%) as a colourless liquid.

[0073] IR (neat): 3018, 2961, 2912, 2837, 1661, 1643, 1434, 1393, 1371, 1298, 1273, 1242, 1095, 1060, 987, 868, 811, 730, 705, 636 cm.sup.1. .sup.1H NMR (CDCl.sub.3): =0.73 (d, J=7.0 Hz, 3H, CH.sub.3), 1.56-1.65 (m, 1H, CH.sub.aH.sub.b), 1.74-1.84 (m, 1H, CH.sub.aH.sub.b), 1.79 (quint, J=1.0 Hz, 3H, CH.sub.3), 1.87 (dq, J=7.0, 1.0 Hz, 3H, CH.sub.3), 1.93-2.14 (m, 2H, CHCH.sub.2CH.sub.2), 2.48-2.56 (m, 1H, CHCHCO), 3.35 (ddd, J=12.0, 5.5, 3.0 Hz, 1H, CHCHCO), 5.60-5.69 (m.sub.3), 5.60-5.69 (m, 2H, 2=CHCH.sub.2), 6.72 (qq, J=7.0, 2.5 Hz, 1H, CHCH.sub.3) ppm. .sup.13C NMR (CDCl.sub.3): =11.2 (q), 14.8 (q), 16.2 (q), 19.1 (t), 25.1 (t), 33.1 (d), 44.2 (d), 126.2 (d), 132.1 (d), 136.3 (d), 137.7 (s), 204.3 (s) ppm. MS: m/z (%)=29 (15), 39 (20), 55 (75), 67 (13), 79 (16), 83 (100), 95 (14), 110 (8), 111 (9), 123 (13), 137 (5), 145 (2), 149 (3), 163 (16), 178 (5, [M.sup.+]).

[0074] Odour description: agrestic, dark fruity, berries, plum, Cyprisate (methyl 1,4-dimethylcyclohexanecarboxylate).

EXAMPLE 8

(2E,1R*,2R*)-2-Methyl-1-(2-methylcyclohex-3-en-1-yl)but-2-en-1-one

[0075] At room temp., a reaction flask was charged with ethanol (200 mL) and sodium (2.49 g, 108 mmol), and the resulting mixture was heated to reflux until all sodium was completely dissolved. (1R*,2S*)-Ethyl 2-methylcyclohex-3-enecarboxylate (91.0 g, 541 mmol), prepared by DielsAlder reaction of ethyl acrylate and (3E)-penta-1,3-diene according to Example 7, was then added with stirring. After the reaction mixture had been stirred at reflux for 15 h, a second portion of sodium (1.24 g, 53.9 mmol) was added, and refluxing was continued for a further 3 h. The reaction mixture was allowed to cool to room temp., and the solvent was evaporated in a rotary evaporator. The resulting residue was taken up in 2-methoxy-2-methylpropan, washed with water (1150 mL) and brine (1150 mL), and then dried over MgSO.sub.4. After filtration and removal of the solvent under reduced pressure, purification of the crude material by distillation in vacuo afforded (1R*,2R*)-ethyl 2-methylcyclohex-3-enecarboxylate (26.8 g, 29%) as colorless liquid.

[0076] In a reaction flask at 70 C. under N.sub.2 atmosphere, an LDA solution was prepared by dropwise addition of a 2.5 M solution of nBuLi in hexanes (12.68 mL, 31.7 mmol) to a stirred solution of iPr.sub.2NH (4.5 mL, 31.7 mmol) in anhydrous THF (15 mL). After stirring for 10 min at 70 C., the cooling bath was removed and the reaction mixture allowed to warm to room temp. within 30 min. Then, at room temp., a 0.5 M solution of 1-methyl-2-propenylmagnesium chloride in THF (86.0 mL, 43.2 mmol) was added dropwise over a period of 1 h, followed by dropwise addition during a period of 2 h of a solution of (1R*,2R*-ethyl 2-methylcyclohex-3-enecarboxylate (5.00 g, 28.8 mmol) in dry THF (45 mL) as prepared above. The resulting reaction mixture was heated to 40 C., and the mixture stirred at this temp. for 18 h. The heating source was removed, and after the reaction mixture had reached room temp., it was poured into ice-cold 2 M NaOH-solution (100 mL), and stirred vigorously for 45 min. The product was extracted with diethyl ether (2200 mL), and the organic extracts were washed with water (2200 mL) and brine (1150 mL). The combined organic extracts were dried with Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure. Purification of the crude product by flash chromatography (300 g silica gel, pentaneether, 39:1; R.sub.f=0.48) and Kugelrohr distillation afforded the title compound (2E,1R*,2R*)-2-methyl-1-(2-methylcyclohex-3-en-1-yl)but-2-en-1-one (1.60 g, 30%) as a colourless liquid.

[0077] IR (neat): 2955, 2928, 1659, 1640, 1453, 1396, 1285, 1236, 1098, 680 cm.sup.1. .sup.1H NMR (CDCl.sub.3): =0.85 (d, J=7.0 Hz, 3H, CH.sub.3), 1.51-1.63 (m, 1H, CH.sub.aH.sub.b), 1.71-1.78 (m, 1H, CH.sub.aH.sub.b), 1.81 (quint, J=1.0 Hz, 3H, CH.sub.3), 1.88 (dq, J=7.0, 1.0 Hz, 3H, CH.sub.3), 2.04-2.13 (m, 2H, CHCH.sub.2CH.sub.2), 2.53-2.68 (m, 1H, CHCHCH.sub.3), 2.91 (ddd, J=12.0, 9.5, 2.5 Hz, 1H, CHCHCH.sub.2), 5.54 (dq, J=10.0, 2.0 Hz, 1H, CHCH), 5.61-5.69 (m, 1H, CHCH.sub.2), 6.73-6.83 (m, 1H, CH.sub.3CH). .sup.13C NMR (CDCl.sub.3): =11.2 (q), 14.8 (q), 20.1 (q), 25.1 (t), 27.4 (t), 32.5 (d), 47.5 (d), 125.0 (d), 133.2 (d), 136.7 (d), 138.5 (s), 205.2 (s). MS: m/z (%)=29 (11), 39 (14), 55 (53), 83 (100), 95 (8), 110 (2), 163 (5), 178 (4) [M.sup.+].

[0078] Odour description: agrestic, dark fruity, berries, plum, Cyprisate (methyl 1,4-di methylcyclohexanecarboxylate).

EXAMPLE 9

Perfume Examples

[0079] A series of perfumes was prepared according to the following formulae. The numbers signify parts by weight:

[0080] First, a base perfume was prepared, according to the following formula

TABLE-US-00001 BENZYL ACETATE EXTRA 10 BENZYL SALICYLATE 150 CINNAMIC ALCOHOL SYNTHETIC 1 CITRONELLOL EXTRA (3,7-dimethyloct-6-en-1-ol) 30 CYCLOHEXAL(4-(4-hydroxy-4-methylpentyl)cyclohex- 60 3-ene-1-carbaldehyde) DIPROPYLENE GLYCOL 49.1 ETHYL LINALOOL 20 EUGENOL RECTIFIED 20 GALAXOLIDE (1,3,4,6,7,8-hexahydro-4,6,6,7,8,8- 45 hexamethylcyclopenta[g]-2-benzopyran) GARDENOL (1-phenylethyl acetate) 4 GERANYL ACETATE ([(2E)-3,7-dimethylocta-2,6- 15 dienyl]acetate) HEDIONE (methyl 3-oxo-2-pentylcyclopentaneacetate) 30 HELIOTROPINE CRYSTALS (1,3-benzodioxole-5- 45 carbaldehyde) HEXENYL-3-CIS SALICYLATE FINE 30 HYDROXYCITRONELLAL SYNTHETIC (7-hydroxy- 7 3,7-dimethyloctanal) INDOLE PURE (1H-indole) 0.4 IONONE BETA (4-(2,6,6-trimethylcyclohexen-1- 65 yl)but-3-en-2-one) IRISONE ALPHA ((E)-4-(2,6,6-trimethyl-1-cyclohex- 15 2-enyl)but-3-en-2-one) ISO E SUPER (1-(2,3,8,8-tetramethyl-1,3,4,5,6,7- 145 hexahydronaphthalen-2-yl)ethanone) LILIAL (3-(4-tert-butylphenyl)butanal) 120 LINALOOL SYNTHETIC (3,7-dimethylocta-1,6-dien-3- 15 ol) LINALYL ACETATE SYNTHETIC (3,7-dimethylocta- 30 1,6-dien-3-yl acetate) LINDENOL (2-(4-methyl-1-cyclohex-3-enyl)propan-2- 5 ol) PHENYL ETHYL ALCOHOL 20 RADJANOL ((E)-2-ethyl-4-(2,2,3-trimethyl-1- 6 cyclopent-3-enyl)but-2-en-1-ol) TAGETES OIL EXTRA 1 THIBETOLIDE (16-oxacyclohexadecan-1-one) 20 VANILLIN (4-hydroxy-3-methoxy-benzaldehyde) 1.5

[0081] To this base perfume, the following ingredients, were added, to provide 5 perfume compositions, labelled A, B, C, D and E. Total parts by weight of the 5 perfumes was 1000.

TABLE-US-00002 PERFUME A B C D E Compound from Example 1 2 20 Compound from Example 2 2 trans-compound from Example 3 .sup.[*.sup.] 2 damascone delta 2 2 DPG 38 38 38 38 18 Total 1000 1000 1000 1000 1000 .sup.[*.sup.] (2E,6R*,7S*)-2-Methyl-1-(7-methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one

[0082] The perfumes were assessed by trained perfumers, and characterised as follows:

[0083] Perfume Afruity, rosy character

[0084] Perfume Bsimilar to Perfume A, but with a slightly less fresh mint contribution

[0085] Perfume Csimilar in freshness to Perfume A, but a fruity agrestic twist

[0086] Perfume Dsimilar to Perfume A, but with a lingering rosy effect, especially noticeable on dry skin

[0087] Perfume Esimilar to Perfume A, but possessing a stronger, rounder, more balanced and overall more pleasant odour. This is because it is possible to use considerably more of the compound of Example 1 (ten times in this instance), than is possible with Damascone compounds, because of the lack of skin sensitisation. This quantity is far in excess of the maximum proportion proposed by the guidelines of IFRA (International Fragrance Asssociation). The lack of skin sensitisation is demonstrated in Examples 12 and 13 hereinunder.

EXAMPLE 10

Perfume Examples in Fabric Conditioner

[0088] A base perfume was prepared according to the following formula (numbers signify parts by weight):

TABLE-US-00003 AMBROFIX ((3aR,5aS,9aS,9bR)-3a,6,6,9a-tetramethyl- 6 2,4,5,5a,7,8,9,9b-octahydro-1H-benzo[e][1]benzofuran) BOURGEONAL (3-(4-tert-butylphenyl)propanal) 40 COSMONE ((5E)-3-methylcyclotetradec-5-en-1-one) 20 FLORHYDRAL (3-(3-propan-2-ylphenyl)butanal) 30 FRESKOMENTHE (2-butan-2-ylcyclohexan-1-one) 100 HEDIONE 180 ISO E SUPER 30 LINALOOL SYNTHETIC 100 MEFROSOL (3-methyl-5-phenylpentan-1-ol) 100 MENTHANYL ACETATE (2-(4-methylcyclohexyl)propan- 100 2-yl acetate) NEROLIONE (1-(3-methyl-2-benzofuran-1- 2 yl)ethanone) @ 10% in DPG PINOACETALDEHYDE (3-(7,7-dimethyl-4- 20 bicyclo[3.1.1]hept-3-enyl)propanal) PRUNOLIDE (5-pentyloxolan-2-one) 6 RADJANOL SUPER ((E)-2-ethyl-4-(2,2,3- 40 trimethyl-1-cyclopent-3-enyl)but-2-en-1-ol) ROSSITOL (1-methyl-3-(2-methylpropyl)-cyclohexanol) 100 SILVANONE SUPRA (cyclopentadecanone/cyclohexadecanone 100 mixture) YLANG YLANG OIL 6

[0089] The base perfume is a fresh, watery, floral, musky accord specifically formulated for use in fabric conditioners.

[0090] To this base perfume, was added the following ingredients, to make Perfumes G, H and I. (Perfume F is the base perfume with only an addition of DPG to make the respective weight proportions equal.)

TABLE-US-00004 PERFUME F G H I Compound from Example 1 20 Compound from Example 2 20 trans-compound from Example 3 .sup.[*.sup.] 20 DPG 20 Total 1000 1000 1000 1000 .sup.[*.sup.] (2E,6R*,7S*)-2-Methyl-1-(7-methylspiro[4.5]dec-8-en-6-yl)but-2-en-1-one

[0091] These perfumes were added at 1% (wt) to a fabric conditioner of the following formula in which the numbers represent parts by weight

TABLE-US-00005 Esterquat cationic surfactant.sup.1 12.00 Soft water 86.65 Calcium chloride 0.30 Antimicrobial.sup.2 0.03 Preservative.sup.3 0.02 Detergent alcohol.sup.4 1.00 .sup.1DEHYQUART AU 57 ex BASF .sup.22-bromo-2-nitropropane (BRONIDOX L ex Cognis) .sup.3benzisothiazolinone (PROXEL GXL ex Lonza) .sup.4Ethoxylated C12-15 alcohol (NEODOL 25-7 ex Shell)

[0092] This was used to wash a load of 3 towels, as follows:

[0093] Machine: Miele Navitronic W3985.

[0094] Washing cycle duration: 16 minutes

[0095] Water temperature: room

[0096] Spin-dry:1200 rpm.

[0097] Fabric conditioner added: 35 g

[0098] The towels were assessed by trained perfumers, and the results were as follows:

[0099] Perfume Ffresh, watery, floral, musky

[0100] Perfume Gadds to Perfume F's qualities an additional clear, fruity, rosy twist, giving it a more pronounced feminine accord with an undertone of gourmand cooked apple

[0101] Perfume Hadds to Perfume F's qualities a fresh mintiness and natural agrestic facette.

[0102] Perfume Iadds to Perfume F's qualities a pleasant fruity, rosy character, especially noticeable on dry cloth.

EXAMPLE 11

Preparation and Application of a Precursor for a Non-Sensitizing Damascone-Type Perfumery Ingredient

[0103] (2E,1R*,2S*)-2-Methyl-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one (cf. Example 1, 1.00 g, 4.85 mmol) and dodecane-1-thiol (930 mg, 4.59 mmol) were dissolved in THF (10 ml), and 1,8-diazabicyclo[5.4.0]undec-7-ene (740 mg, 4.86 mmol) was added. The resulting solution was stirred at room temperature for 22 h, then poured into ice-cold 2 M aqueous HCl-solution (40 ml). The product was extracted with methyl t-butyl ether (250 mL). The combined organic layers were washed with brine, dried over MgSO.sub.4, aand concentrated under reduced pressure. The resulting residue was purified by flash chromatography (90 g silica gel, hexane/methyl t-butyl ether, 100:1) to yield the product as a colourless oil (750 mg, 38%) as a mixture of diastereomers.

[0104] MS for diastereomers 11.1-11.5 (area-% by GC): Diastereomer 9.1 (33%): m/z (%)=29 (22), 41 (29), 55 (51), 83 (100), 132 (30), 229 (42), 257 (27), 285 (6), 408 (<1, M.sup.+); diastereomer 11.2 (27%): m/z (%)=29 (10), 41 (20), 55 (34), 83 (100), 123 (16), 229 (24), 257 (14), 285 (3), 408 (<1, M.sup.+); diastereomer 11.3 (11%): m/z (%)=29 (18), 41 (32), 55 (51), 83 (100), 123 (29), 229 (48), 257 (24), 285 (5), 408 (<1, M.sup.+); diastereomer 11.4 (11%): m/z (%)=29 (14), 41 (29), 55 (33), 69 (18), 83 (100), 123 (16), 206 (7), 243 (30), 257 (4), 408 (<1, M.sup.+); diastereomer 11.5 (8%): m/z (%)=29 (14), 43 (32), 55 (55), 69 (18), 83 (100), 123 (34), 229 (56), 257 (32), 285 (8), 408 (<1, M.sup.+).

[0105] For the demonstration of the long-lasting release properties of a non-sensitizing Damascone-like fragrance ingredient, two fabric conditioner samples A and B were prepared as follows:

[0106] To an unperfumed fabric conditioner base as described in Example 10 (15.9 g) was added a mixture of dipropylene glycol (144 mg) and either (2E,1R*,2S*)-2-methyl-(2,6,6-trimethylcyclohex-3-en-1-yl)but-2-en-1-one (cf. Example 1, 16.0 mg, Sample A) or the precursor as above prepared (16.0 mg, Sample B).

[0107] Two standard wash/rinse cycles were carried out contemporarily, each with a 1 kg load of cotton terrycloth towels in European front-loading washing machines, using an unperfumed powder detergent (35.0 g) for the wash cycles and the above described fabric conditioner samples A and B for the rinse cycles.

[0108] The odour intensity of the towels was judged by a panel of 6 expert assessors on a scale of 0 (odourless) to 5 (very strong) at wet stage and after 4 days (1 day line dry, then folded and left at room temperature in ambient air). The results are summarized in the following Table.

TABLE-US-00006 Paired mean Paired mean Student's intensity Student's intensity t-test score after t-test Sample score on wet (wet) 4 days (4 days) A (free odorant) 2.5 p = 1.5 p = B (precursor) 2 0.6 2.2 0.008

[0109] The results show that at wet stage, the free odorant imparted a slightly higher odour intensity to the towels, the difference was however not significant. After 4 days, the towels rinsed with the precursor containing fabric conditioner sample had a significantly higher intensity score. The odour quality was described as fruity, floral, Damascone-like.

EXAMPLE 12

Demonstration of Reduced Sensitisation of Compounds

[0110] Compounds were tested using the commercial KeratinoSens assay for skin sensitization.

[0111] The compound of Example 1 (Example 1) was compared with Damascone delta.

[0112] FIG. 1 shows the gene-induction and cell viability curves for Damascone delta and Example 1, in which the black diamonds indicate the induction of the luciferase activity and the open squares Cellular viability.

[0113] Example 1 did not induce luciferase activity above the 1.5-fold threshold, and is thus rated as non-sensitizing by this assay. Damascone delta on the other hand clearly induces the luciferase gene already at 4 micromolar, indicating it is a significantly sensitizing compound and maximal gene induction reaches 8.7-fold over control. These results show that Example 1 can be used in perfume formulations for reduced sensitization risk to the consumer. Table 1 shows the results of other compounds according to this disclosure, as compared with Damascone delta. With the exception of example 6, none of the inventive compounds induced the gene above the threshold of 1.5-fold at non-cytotoxic concentrations, while the maximal gene induction was at 8.7 for Damascone delta. A marginal gene induction (1.67-fold at 125 M only) was noted for example 6. This indicates that all inventive compounds have a strongly reduced sensitization potential as compared to Damascone delta.

TABLE-US-00007 Imax (fold Concentration for 1.5- Concentration for 50% maximal gene fold gene induction Cytotoxicity induction) (EC 1.5 in M) (in M) Damascone delta 8.77 3.96 40.47 Compound of Example 1 1.09 n.i. 90.3 Compound of Example 2 1.28 n.i. 112.1 (2E,6R*,7R*)-2-Methyl- 1.12 n.i. 48.8 1-(7-methylspiro[4.5]dec- 8-en-6-yl)but-2-en-1-one (Example 3) (2E,6R*,7S*)-)-2-Methyl- 1.19 n.i. 21.4 1-(7-methylspiro[4.5]dec- 8-en-6-yl)but-2-en-1-one (Example 3) Compound of Example 4 1.36 n.i. 176.2 Compound of Example 5 1.51 Induction only 77.5 below 70% viability Compound of Example 6 1.64 48.8 89.3 (2E,1R*,2S*)-2-Methyl- 1.26 n.i. 339.8 1-(2-methylcyclohex-3- en-1-yl)but-2-en-1-one (Example 7) (2E,1R*,2R*)-2-Methyl- 1.35 n.i. 316.4 1-(2-methylcyclohex-3- en-1-yl)but-2-en-1-one (Example 8) n.i. no induction above threshold of 1.5

EXAMPLE 13

Compounds Tested in the a Peptide Reactivity Assay for Skin Sensitization

[0114] A second method to determine allergenic potential of chemicals is the DPRA direct peptide assay (OECD TG 442c). It is based on the fact that allergenic chemicals must react with a peptide/protein in order to be immunogenic.

[0115] A peptide reactivity assay (A. Natsch, H. Gfeller, Toxicol. Sci 2008, 106, 464-478) was conducted similarly to the DPRA assay: The test chemicals were dissolved to a final concentration of 4 mM in acetonitrile and 250 l of this solution were added to 2 ml HPLC vials. The test peptide Cor1C-420 with the sequence Ac-NKKCDLF (Genscript Inc., Piscataway, N.J., USA), was dissolved at 0.133 mM in 20 mM phosphate buffer at pH 7.5, and 750 l of this solution were added to each test vial (final concentrations: 1 mM of test chemical and 0.1 mM of peptide in 25% acetonitrile; ratio 1:10 as in the DPRA assay). The samples were incubated for 1-24 h at 37 C. and at regular intervals they were analysed by LC-MS analysis on a VELOS PRO Mass spectrometer (Thermo SCIENTIFIC, San Jose, Calif., U.S.A.) operated in the ESl(+) mode. The temperature of the capillary was kept at 275 C. Mass spectra were recorded from 200-2000 amu. A ZORBAX Eclipse XDB-C18 column, 2.1 mm ID, 150 mm, 5-Micron (Agilent Technologies) was used. The mobile phase consisted of H.sub.2O (A) and methanol (B) each containing 0.1% formic acid (v/v). The solvent flow was 250 l/min and the following gradient (ratio A: B) was used: 0 min, 95:5; 2 min, 40:60; 10 min, 2:98; 12 min, 2:98. The integration was performed with Xcalibur Quan Browser.

[0116] Two endpoints are measured with this assay:

[0117] a) Depletion of the parent peptide. The mass of the protonated parent peptide is measured and the corresponding peak integrated (% depletion; FIG. 2). Depletion of the parent peptide is indicative of reactivity and is described as endpoint in OECD guideline 442c.

[0118] b) Formation of modified peptides. The specific ion trace for a new adduct with the mass of the test chemical added to the test peptide is extracted, and the peak of the peptide-adduct is integrated (FIG. 3). Peptide adduct formation is a particular sensitive endpoint to determine reactive, and thus allergenic nature of compounds.

[0119] FIGS. 2 (peptide depletion) and 3 (adduct formation on a logarithmic scale) compare the 5 peptide reactivity of two commercial damascones with the compound of Example 1 (Example 1). After 1 h, Example 1 produces 3200-fold lower levels of peptide adducts as compared to Damascone delta, and no significant peptide depletion is noted over the 24 h experiment, indicating a dramatic and unexpected reduction of reactivity (and thus allergenicity) for Example 1.