Organic Compounds

Abstract

A compound of formula I

##STR00001##

wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 can be independently selected from H or Me,
n=0, 1,
the dotted lines are indicating single bonds, or in case n=0 an isolated double bond at position 3, or in case n=1 an isolated double bond at position 3 or 4,
and the wavy bond is indicating an unspecified configuration of the adjacent double bond. Said compounds, as well as precursors capable to generate said compounds, are useful as fragrance ingredients.

Claims

1. A compound of formula I ##STR00017## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 can be independently selected from H or Me, n=0, 1, the dotted lines are indicating single bonds, or in case n=0 an isolated double bond at position 3, or in case n=1 an isolated double bond at position 3 or 4, and the wavy bond is indicating an unspecified configuration of the adjacent double bond.

2. A compound according to claim 1 selected from the group consisting of (1s*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-but-2-enoate, (1s*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-2-methylbut-2-enoate, (1R*,2S*,6R*)-2-ethyl-6-methylcyclohex (E)-but-2-enoate, (1S*,2S*)-2,6,6-trimethylcyclohex-3-en-1-yl (E)-but-2-enoate, (1R*,2S*,6R*)-2,6-dimethylcyclohex-3-en-1-yl (E)-but-2-enoate and (1s*,2R*,5S*)-2,5-dimethylcyclopentyl (E)-but-2-enoate.

3. (canceled)

4. A fragrance composition comprising a compound according to claim 1, or a mixture thereof.

5. A fragrance composition according to claim 4 comprising at least one other fragrance ingredient.

6. A consumer product comprising a compound according to claim 1 or a fragrance composition according to claim 4, and a consumer product base.

7. A consumer product according to claim 5 selected from fine perfumery, household products, laundry products, body care products, cosmetic and air care products.

8. A method of improving, enhancing or modifying a consumer product by means of addition thereto of an olfactory acceptable amount of a compound of formula I as defined in claim 1.

9. A precursor adapted to generate a compound according to formula (I) as defined in claim 1, having the formula (II) ##STR00018## in which R.sub.1, R.sub.2, R.sub.3 and R.sub.4 can be independently selected from H or Me, n=0, 1, the dotted lines are indicating single bonds, or in case n=0 an isolated double bond at position 3, or in case n=1 an isolated double bond at position 3 or 4, the substituents at the ring system are having an all-syn relationship, and in which X is selected from SR.sup.5, NHR.sup.6 and NR.sup.6R.sup.7, 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.

10. (canceled)

11. (canceled)

Description

EXAMPLES

Example 1: (1s*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-but-2-enoate

[0078] ##STR00008##

[0079] a) Sodium borohydride (18.6 g, 499 mmol) was added portion wise to a solution of 2,6-dimethylcyclohexanone (90.0 g, 713 mmol, mixture of isomers) in methanol (300 ml) at 20 C. After complete addition, the cooling bath was removed and stirred for 1 hour. The reaction mixture was diluted with MTBE (300 ml) and poured into 2M HCl (200 ml). The organic phase was washed with water and (200 ml) and brine (200 ml), dried (MgSO.sub.4) and concentrated in vacuo to yield the product as a mixture of diastereomers (82.9 g) as a clear slightly yellow liquid. From 12.0 g of the crude product, (1s*,2R*,6S*)-2,6-dimethylcyclohexanol (3.85 g, 29%) was isolated by chromatography over silica gel (hexane:MTBE=9:1).

[0080] b) To a cooled (0 C.) solution of (1s*,2R*,6S*)-2,6-dimethylcyclohexanol (3.00 g, 23.40 mmol) in THF (60 ml) was added a catalytic amount of 1,10-phenanthroline and butyl lithium (14.6 ml, 1.6 M solution in hexane). The color of the solution gradually turned from yellow to brown and the internal temperature rose to 6 C. A solution of crotonyl chloride (3.26 g, 28.10 mmol) in THF (20 ml) was added dropwise while the temperature rose to 30 C. The mixture was stirred for another 15 min at room temperature. Then MTBE (80 ml) and 2M HCl (80 ml) were added. The organic phase was washed with water (80 ml) and brine (80 ml), dried (MgSO.sub.4) and concentrated in vacuo. The residue (4.40 g of a yellowish oil) was purified by chromatography over silica gel (hexane:MTBE=99:1) and Kugelrohr distillation (120 C., 0.06 mbar) to yield (1s*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-but-2-enoate (2.1 g, 46%) as a colorless oil.

[0081] .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm 6.98 (dq, J=15.6, 6.9 Hz, 1H) 5.88 (dq, J=15.6, 1.71 Hz, 1H) 5.08 (t, J=2.2 Hz, 1H) 1.89 (dd, J=6.8, 1.71 Hz, 3H) 1.71-1.77 (m, 1H) 1.57-1.69 (m, 2H) 1.20-1.46 (m, 5H) 0.83 (d, J=6.8 Hz, 6H). .sup.13C-NMR (101 MHz, CDCl.sub.3) b ppm 166.7 (s) 143.9 (d) 123.1 (d) 76.1 (d) 36.4 (d, 2C) 28.6 (t, 2C) 25.8 (t) 18.3 (q, 2C) 17.9 (q). GC/MS (EI): 110 (M+, C.sub.4H.sub.6O.sub.2, 32), 109 (13), 95 (36), 69 (100), 55 (14), 41 (23), 32 (16).

[0082] Odor: baked apple, pineapple, plum jam, creamy, damascenone

Comparative Example 2: (2R*,6R*)-2,6-dimethylcyclohexyl (E)-but-2-enoate

[0083] ##STR00009##

[0084] a) In an autoclave, neat 2,6-dimethylcyclohexanone (900 g, 7.13 mol) was hydrogenated over carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)-amino]ruthenium(II) (Ru-MACHO, CAS 1295649-40-9) (0.5 g) during 3 h at 50 bar and 80 C. The reaction product, consisting of the (1s*,2R*,6S*)- and the (2R*,6R*)-2,6-dimethylcyclohexan-1-ol isomers in a ratio of 67:33, was fractionated over a 100 cm Sulzer column to yield (2R*,6R*)-2,6-dimethylcyclohexanol (41 g, bp. 43 C./5 mbar).

[0085] b) (2R*,6R*)-2,6-Dimethylcyclohexyl (E)-but-2-enoate was synthesized from (2R*,6R*)-2,6-dimethylcyclohexanol and (E)-but-2-enoyl chloride in a yield of 68% according to Example 1.

[0086] 1H NMR (400 MHz, CDCl.sub.3) ppm 7.28 (s, 1H) 6.98 (dq, J=15.5, 7.0 Hz, 1H) 5.88 (dq, J=15.5, 1.7 Hz, 1H) 4.65 (dd, J=8.1, 3.9 Hz, 1H) 2.06-2.15 (m, 1H) 1.90 (dd, J=7.0, 1.7 Hz, 3H) 1.69-1.77 (m, 1H) 1.41-1.58 (m, 4H) 1.10-1.20 (m, 1H) 0.92 (dd, J=6.8, 2.4 Hz, 6H). 13C NMR (101 MHz, CDCl.sub.3) ppm 166.2 (s) 143.9 (d) 123.3 (d) 79.2 (d) 31.3 (d) 30.9 (d) 30.5 (t, 2C) 19.8 (t) 17.9 (q) 17.7 (q) 14.3 (q). GC/MS (EI): 110 (M+, C.sub.4H.sub.6O.sub.2, 53), 109 (5), 95 (76), 69 (100), 82 (8), 81 (8), 55 (10), 41 (29), 39 (17).

[0087] Odor: Fruity, metallic, animalic, crotonic

Comparative Example 3: (1r*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-but-2-enoate

[0088] ##STR00010##

[0089] a) A solution of (1s*,2R*,6S*)-2,6-dimethylcyclohexanol (10.0 g, 78 mmol, prepared as described in Example 1, step a) in acetone (100 ml) was cooled to 5 C. and Jones reagent (19.5 ml) was added dropwise (temperature rose to 20 C.). The mixture is stirred for another 30 min, and isopropanol (10 ml) is added dropwise and left stirring for another 10 min. The reaction mixture was diluted with MTBE (150 ml) and poured on 2M NaOH (100 ml). The organic phase was washed with water (100 ml) and brine (2100 ml), dried (MgSO.sub.4) and concentrated in vacuo to afford (2R*,6S*)-2,6-dimethylcyclohexanone (9.0 g, 91%) as a clear colorless liquid.

[0090] b) A solution of (2R*,6S*)-2,6-dimethylcyclohexanone (10.0 g, 79 mmol) in methanol (100 ml) was cooled to 5 C. and sodium borohydride (2.10 g, 55.5 mmol) was added in 3 portions (temperature rose to 20 C.). The cooling bath was removed and the mixture stirred for 30 min, diluted with MTBE (150 ml) and poured onto 2M NaOH (100 ml). The organic phase was washed with water (100 ml) and brine (2100 ml), dried (MgSO.sub.4) and concentrated in vacuo to yield a diastereomeric mixture of 2,6-dimethyl cyclohexanols (7.7 g). (1r*,2R*,6S*)-2,6-Dimethylcyclohexanol (1.80 g, 17.7%) was isolated from the mixture by chromatography on silica gel (hexane:MTBE=87:13) and recrystallization as colorless crystals.

[0091] c) To a cooled (0 C.) solution of (1r*,2R*,6S*)-2,6-dimethylcyclohexanol (1.80 g, 14.04 mmol) in THF (50 ml) was added a catalytic amount of 1,10-phenanthroline and butyl lithium (8.8 ml, 1.6 M solution in hexane). The color of the solution gradually turned from yellow to brown and the internal temperature rose to 6 C. A solution of crotonyl chloride (1.96 g, 16.85 mmol) in THF (20 ml) was added dropwise while the temperature rose to 20 C. The mixture was stirred for another 15 min at room temperature. Then MTBE (80 ml) and 2M HCl (80 ml) were added. The organic phase was washed with water (80 ml) and brine (80 ml), dried (MgSO.sub.4) and concentrated in vacuo. The residue (3.16 g of a yellowish oil) was purified by chromatography over silica gel (hexane:MTBE=99:1) and Kugelrohr distillation (120 C., 0.06 mbar) to yield (1r*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-but-2-enoate (0.71 g, 25%) as a colorless oil.

[0092] .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm 7.00 (dq, J=15.4, 6.9 Hz, 1H) 5.89 (dq, J=15.7, 1.7 Hz, 1H) 4.38 (t, J=10.3 Hz, 1H) 1.90 (dd, J=6.9, 1.7 Hz, 3H) 1.72-1.79 (m, 2H) 1.61-1.68 (m, 1H) 1.49-1.61 (m, 1H) 1.22-1.36 (m, 1H) 1.05-1.18 (m, 2H) 0.86 (d, J=6.6 Hz, 6H). .sup.13C-NMR (101 MHz, CDCl.sub.3) 5 ppm 166.7 (s) 144.3 (d) 122.9 (d) 82.6 (d) 37.9 (d, 2C) 33.9 (t, 2C) 25.3 (t) 18.5 (q, 2C) 17.9 (q). GC/MS (EI): 110 (M+, C4H6O2, 36), 95 (26), 82 (6), 69 (100), 55 (7), 41 (22), 39 (13).

[0093] Odor: Fruity metallic, crotonic

Example 4: (1s*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-2-methylbut-2-enoate

[0094] ##STR00011##

[0095] This compound was synthesized from (1s*,2R*,6S*)-2,6-dimethylcyclohexanol and (E)-2-methylbut-2-enoyl chloride in a yield of 68% according to Example 1.

[0096] .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm 6.89 (qq, J=7.1, 1.5 Hz, 1H) 5.10 (br s, 1H) 1.88-1.87 (m, 3H) 1.82 (dq, J=7.1, 1.5 Hz, 3H) 1.61-1.69 (m, 2H) 1.22-1.51 (m, 6H) 0.84 (d, J=6.8 Hz, 6H). .sup.13C-NMR (101 MHz, CDCl.sub.3) ppm 168.2 (s) 136.5 (d) 128.9 (s) 76.4 (d)

[0097] 36.5 (d, 2C) 28.8 (t, 2C) 25.9 (t) 18.4 (q) 14.3 (q) 12.2 (q). GC/MS (EI): 110 (M.sup.+, C.sub.5H.sub.8O.sub.2, 43), 109 (7), 101 (8), 95 (32), 83 (100), 69 (14), 55 (38), 41 (12), 39 (8).

[0098] Odor: fruity, red fruits

Example 5: (1R*,2S*,6R*)-2-ethyl-6-methylcyclohexyl (E)-but-2-enoate

[0099] ##STR00012##

[0100] a) A solution of 2-ethyl-6-methylphenol (25 g, 184 mmol) in hexane (20 ml) was hydrogenated in an autoclave over Pd on carbon (10%, 0.2 g) during 48 h at 50 bar and 100 C. The mixture was filtered over a pad of silica gel and concentrated in vacuo to yield 2-ethyl-6-methylcyclohexanone as a slightly turbid oil (24.38 g) which was used directly in the next step.

[0101] b) In an autoclave, neat 2-ethyl-6-methylcyclohexanone (24 g, 174 mol) was hydrogenated over carbonylhydrido(tetrahydroborato)[bis(2-diphenylphosphinoethyl)-amino]ruthenium(II) (Ru-MACHO, CAS 1295649-40-9; 10 mg) during 21 h at 50 bar and 80 C. The crude reaction product (21.2 g), consisting of a mixture of isomers, was purified by chromatography (SiO.sub.2, hexane:MTBE=87:13) to yield diastereomerically pure (1R*,2S*,6R*)-2-ethyl-6-methylcyclohexan-1-ol (3.71 g, 15%) which was used directly in the next step.

[0102] c) (1R*,2S*,6R*)-2-ethyl-6-methylcyclohexan-1-ol (1.75, 12.3 mmol) was esterified according to Example 1b.

[0103] (1R*,2S*,6R*)-2-Ethyl-6-methylcyclohexyl (E)-but-2-enoate: .sup.1H-NMR (400 MHz, CDCl.sub.3) b ppm 6.96 (dq, J=15.4, 6.8 Hz, 1H) 5.86 (dq, J=15.5, 1.7 Hz, 1H) 5.18 (bs, 1H) 1.87 (dd, J=6.8, 1.8 Hz, 3H) 1.49-1.78 (m, 3H) 1.19-1.48 (m, 6H) 1.07-1.16 (m, 1H) 0.87 (d, J=7.3 Hz, 3H), 0.82 (d, J=6.8 Hz, 3H). .sup.13C-NMR (101 MHz, CDCl.sub.3) ppm 166.5 (s) 143.9 (d) 123.0 (d) 74.3 (d) 43.6 (d) 36.4 (d) 29.0 (t) 26.6 (t) 25.8 (t) 25.5 (t) 18.4 (q) 17.9

[0104] (q) 11.6 (q). GC/MS (EI): 210 (M.sup.+, <1), 181 (2), 124 (22), 109 (4), 95 (58), 82 (8), 69 (100), 55 (16), 41 (34), 29 (6).

[0105] Odor: fruity, saffron, plum, damascone-like, apple

Example 6a: (1S*,2S*)-2,6,6-Trimethylcyclohex-3-en-1-yl (E)-but-2-enoate and Comparative Example 6b: (1S*,2R*)-2,6,6-trimethylcyclohex-3-en-1-yl (E)-but-2-enoate

[0106] ##STR00013##

[0107] a) A few ml of a solution of (E)-1-chlorobut-2-ene (25.6 g, 282 mmol) in THF (200 ml) were added to magnesium turnings (8.58 g, 353 mmol) in THF (100 ml) under argon atmosphere. After the reaction had started, the rest of the chlorobutene solution was added dropwise. The mixture was allowed to cool to room temperature and a solution of 2,2-dimethylpent-4-enal (40.0 g, 66% solution in toluene, 235 mmol) in THF (50 ml) was added slowly. The mixture was cooled to 0 C. and quenched with aq. NH.sub.4Cl (200 ml). The organic layer was separated and the aqueous layer was extracted with ethyl acetate (3200 mL). The combined organic layers were washed with brine, dried (MgSO.sub.4) and concentrated in vacuo. The residue was distilled bulb-to-bulb (0.14 mbar, 140 C.) to yield 20.0 g of 3,5,5-trimethylocta-1,7-dien-4-ol as a colorless oil.

[0108] b) To a 250 ml single-neck round-bottomed flask was added above product, dissolved in toluene (20 ml), and Zhan Catalyst-1B (CAS 918870-76-5; 0.346 g, 0.471 mmol) under Ar atmosphere. The reaction was heated to 80 C. for 1 h. Then, the solvent was evaporated and the residue purified by chromatography on silica gel (hexane:MTBE=100:1) and distilled bulb-to-bulb to give 5.0 g of 2,6,6-trimethylcyclohex-3-enol (syn/anti isomers in a ratio of 58:42) as a colorless oil.

[0109] c) To a solution of methylmagnesium bromide (7.84 ml, 23.53 mmol) in THF (20 ml) was added 2,6,6-trimethylcyclohex-3-enol (syn/anti isomers in a ratio of 58:42, 3.00 g, 21.4 mmol) dropwise at 10 C. under argon atmosphere. Then, (E)-but-2-enoyl chloride (3.35 g, 32.1 mmol) was added slowly at this temperature. The mixture was stirred for 1 h at room temperature, poured onto water (100 mL) and extracted with MTBE (3100 mL). The combined organic layers were dried (MgSO.sub.4) and concentrated in vacuo. The residue was purified by chromatography (silica gel, hexane:MTBE=100:1) and Kugelrohr distillation to (0.13 mbar, 83 C.) to give (1S*,2S*)-2,6,6-trimethylcyclohex-3-en-1-yl (E)-but-2-enoate (1.00 g 22%) and (1S*,2R*)-2,6,6-trimethylcyclohex-3-en-1-yl (E)-but-2-enoate (0.5 g, 11%), both as colorless oils.

[0110] (1S*,2S*)-Isomer: .sup.1H NMR (300 MHz, CDCl.sub.3) ppm 6.96 (dq, J=15.7, 7.0 Hz, 1H) 5.87 (dq, J=15.7, 1.6 Hz, 1H) 5.65 (dddd, J=10.1, 5.0, 2.4, 2.4 Hz, 1H) 5.34 (br d, J=10.1 Hz, 1H) 4.87 (d, J=3.6 Hz, 1H) 2.45-2.56 (m, 1H) 2.08 (br dd, J=17.5, 3.0 Hz, 1H) 1.87 (dd, J=7.0, 1.6 Hz, 3H) 1.68 (br dd, J=17.5, 4.4 Hz, 1H) 0.95 (s, 3H) 0.93 (d, J=7.2 Hz, 3H) 0.87 (s, 3H). .sup.13C NMR (75 MHz, CDCl.sub.3) ppm 166.7 (s) 144.4 (d) 128.4 (d) 125.2 (d) 122.9 (d) 77.5 (d) 34.9 (t) 33.5 (s) 31.6 (d) 27.1 (q) 24.9 (q) 17.9 (q) 16.1 (q).

[0111] GC/MS (EI): 208 (M.sup.+, <1), 140 (42), 122 (27), 107 (31), 91 (6), 69 (100), 55 (5).

[0112] (1S*,2R*)-Isomer: .sup.1H NMR (300 MHz, CDCl.sub.3) ppm 7.00 (dq, J=15.3, 6.8 Hz, 1H) 5.89 (dq, J=15.3, 1.5 Hz, 1H) 5.48-5.56 (m, 1H) 5.41 (d, J=9.8 Hz, 1H) 4.70 (d, J=9.4 Hz, 1H) 2.33-2.23 (m, 1H) 2.14-2.04 (m, 1H) 1.90 (dd, J=6.8, 1.5 Hz, 3H) 0.96 (d, J=7.0 Hz, 3H) 0.95 (s, 3H), 0.88 (s, 3H). .sup.13C NMR (75 MHz, CDCl.sub.3) ppm 166.6 (s) 144.4 (d) 130.4 (d) 124.6 (d) 122.9 (d) 81.1 (d) 40.2 (t) 34.0 (s) 33.9 (d) 27.2 (q) 20.0 (q) 18.1 (q) 17.9 (q). GC/MS (EI): 208 (M.sup.+, <1), 140 (41), 122 (25), 107 (28), 91 (6), 69 (100), 55 (5).

[0113] Odor (1S*,2S*)-Isomer: fruity green, damascone, stronger than the (1S*,2R*) derivative Odor (1S*,2R*)-Isomer: weaker, fruity, slightly crotonic

Example 7: (1R*,2S*,6R*)-2,6-Dimethylcyclohex-3-en-1-yl (E)-but-2-enoate

[0114] ##STR00014##

[0115] a) Sodium borohydride (0.19 g, 5.13 mmol) was added to a solution of 2,6-dimethylcyclohex-3-enone (0.91 g, 7.33 mmol, mixture of isomers) in methanol (20 ml). The temperature was kept at 30 C. by means of a water bath. After 1 h, the mixture was poured into diluted HCl (20 ml, 2 M) and extracted twice with MTBE (40 ml). The combined organic phases were washed with water (40 ml) and brine (40 ml), dried (MgSO.sub.4) and concentrated in vacuo to yield a colorless clear oil (0.41 g) which was purified by chromatography over silica gel (hexane:MTBE=84:16) to afford 0.22 g of a colorless oil from which (1R*,2S*,6R*)-2,6-dimethylcyclohex-3-en-1-ol (0.13 g) solidified in form of colorless crystals which were used directly in the next step.

[0116] b) A solution of (1R*,2S*,6R*)-2,6-dimethylcyclohex-3-en-1-ol (0.13 g, 1.30 mmol) and a spatula tip of 1,10-phenantroline in THF (20 ml) were cooled to 10 C. Then, 0.7 ml buthyllithium (1.6M in hexane) were added (the temperature rose to 5 C. and the color changed from yellow to dark brown). The mixture was stirred for 10 min, followed by addition of crotonyl chloride (0.13 g, 1.13 mmol). After completed addition, the cooling bath was removed and the mixture was stirred for 30 min and poured into aq. HCl (20 ml, 2M) and extracted two times with MTBE (20 ml). The organic layer was washed with water (20 ml) and brine (20 ml), dried over MgSO.sub.4 and evaporated in vacuo to yield 0.27 g of an clear, yellow liquid which was purified by a flash chromatography over silica gel (hexane/MTBE 50:1) to yield (1R*,2S*,6R*)-2,6-dimethylcyclohex-3-en-1-yl (E)-but-2-enoate (0.11 g, 55%) as a colorless oil.

[0117] .sup.1H NMR (600 MHz, BENZENE-d.sub.6) ppm 6.9 (dq, J=15.4, 6.9 Hz, 1H) 5.8 (dq, J=15.4, 1.6 Hz, 1H) 5.7 (ddt, J=10.2, 5.0, 2.6, 2.6 Hz, 1H) 5.3-5.3 (m, 2H) 2.26-2.20 (m, 1H) 1.96-1.89 (m, 1H) 1.82-1.76 (m, 1H) 1.67-1.61 (m, 4H) 1.29 (dd, J=6.8, 1.9 Hz, 3H) 1.0 (d, J=7.2 Hz, 3H) 0.9 (d, J=6.8 Hz, 3H). .sup.13C-NMR (151 MHz, C.sub.6D.sub.6) ppm 166.2 (s) 144.0 (d) 129.8 (d) 126.1 (d) 123.3 (d) 73.6 (d) 35.5 (d) 32.8 (d) 29.3 (t) 18.3 (q) 17.4 (q) 16.6 (q). GC/MS (EI): 18.3 (q, 2C) 17.9 (q). GC/MS (EI): 194 (M.sup.+, 1), 126 (9), 108, (48), 93 (21), 81 (6), 69 (100), 55 (7), 41 (18).

[0118] Odor: pleasant apple, plum jam, creamy, damascenone

Example 8: (1s*,2R*,5S*)-2,5-dimethylcyclopentyl (E)-but-2-enoate+stereoisomers

[0119] ##STR00015##

[0120] a) Dimethyl carbonate (224.8 g, 2.5 mol) was added to a suspension of sodium hydride (60% in oil, 125 g, 3.11 mol) in THF (500 ml) and the resulting mixture was heated to reflux and treated dropwise within 1.5 h with a solution of 98% pure 2-methyl cyclopentanone (100 g, 1 mol) in THF (500 ml). The resulting mixture was stirred at reflux for 45 min, cooled to 5 C., and treated dropwise within 1 h with an aqueous solution of 3M AcOH (1 l). The mixture was then acidified to pH 1 by addition of conc. HCl. and the resulting mixture was treated with aq. sat. NaCl soln. (0.5 l) and extracted with MTBE (1 l). The water phase was extracted twice with MTBE (0.5 l) and the combined organic phases were washed with brine, dried (MgSO.sub.4) and concentrated. The crude product (233 g, yellow oil) was purified by short-path distillation (0.1 mbar; oil bath temperature: 100 C., boiler temp: 85 C., head temp: 80 C.) leading to 3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester (162 g, quant., colorless oil, ratio of diastereomers=48:52).

[0121] b) A mixture of 3-methyl-2-oxo-cyclopentanecarboxylic acid methyl ester (10 g, 0.064 mol), methyl iodide (27.2 g, 0.192 mol), and potassium carbonate (35.4 g, 0.256 mol) in acetone (100 ml) was refluxed for 1 h, cooled to 20 C., poured into 2N HCl/ice and extracted twice with MTBE (100 ml). The combined organic phases were washed with brne, dried (MgSO.sub.4), and concentrated affording crude 1,3-dimethyl-2-oxo-cyclopentanecarboxylic acid methyl ester (9.4 g, yellow oil, 89% yield over 2 steps, 1:2 mixture of diastereomers).

[0122] c) A mixture of 1,3-dimethyl-2-oxo-cyclopentanecarboxylic acid methyl ester (9.4 g, 0.055 mol), acetic acid (130 ml), conc. sulfuric acid (35 ml) and water (50 ml) was refluxed for 1.25 h, cooled to 20 C., poured over 2N NaOH/ice and extracted three times with diethyl ether (200 ml). The combined organic phases were washed with brine, dried (MgSO.sub.4), and concentrated. The crude product (5.6 g, orange oil) was purified by Kugelrohr distillation (80 C., 24 mbar) yielding 2,5-dimethylcyclopentanone (4.2 g, colorless oil, 68% yield, 61% yield over 3 steps, cis/trans ratio=1:2).

[0123] d) At 0 C., a solution of 2,5-dimethylcyclopentanone (4.2 g, 0.0374 mol) in ethanol (25 ml) was added dropwise to a mixture of NaBH.sub.4 (1 g, 0.0262 mol) in ethanol (25 ml). The resulting mixture was stirred for 2 h, poured over 2N HCl/ice and extracted three times with diethyl ether (100/50/50 ml). The combined organic phases were washed with brine, dried (MgSO.sub.4), and concentrated to yield crude 2,5-dimethylcyclopentanol (5.0 g, colorless oil, mixture of isomers=23:9:68).

[0124] Major isomer (68%, cis, trans): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm selected signal 3.60 (dd, J=4.2, 5.7, 1H). .sup.13C-NMR (100 MHz, CDCl.sub.3) ppm 82.2 (d) 41.3 (d) 37.1 (d) 30.8 (t) 30.7 (t) 19.4 (q) 14.0 (q). GC/MS (EI): 114 (M.sup.+, 23), 99 (4), 96 (14), 81 (37), 71 (100), 58 (70), 57 (89), 43 (27), 41 (23), 29 (10).

[0125] Second major isomer (23%, trans, trans): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm selected signal 3.03 (t, J=8.2, 1H). .sup.13C-NMR (100 MHz, CDCl.sub.3) ppm 86.8 (d) 41.8 (d) 29.2 (t) 18.2 (q).

[0126] GC/MS (EI): 114 (M.sup.+, 27), 99 (4), 96 (14), 81 (36), 71 (100), 58 (70), 57 (87), 43 (29), 41 (22), 29 (10).

[0127] Minor isomer (9%, cis, cis): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm selected signal 3.74 (t, J=3.8, 1H). .sup.13C-NMR (100 MHz, CDCl.sub.3) ppm 78.9 (d) 39.9 (d) 30.2 (t) 14.3 (q). GC/MS (EI): 114 (M.sup.+, 22), 99 (5), 96 (15), 81 (36), 71 (100), 58 (68), 57 (88), 43 (27), 41 (24), 29 (11).

[0128] e) A solution of crude 2,5-dimethylcyclopentanol (5.0 g, 0.0374 mol max.) and DMAP (0.46 g, 3.7 mmol) in cyclohexane (100 ml) and pyridine (5.92 g, 7.5 mmol) was treated dropwise with crotonyl chloride (6.5 g, 56.2 mmol, 90% pure). The resulting mixture was stirred for 5.5 h at 20 C., poured over aq. sat. NaHCO.sub.3/ice and extracted three times with MTBE (200/100/100 ml). The combined organic phases were washed with 2N HCl, water, brine, dried (MgSO.sub.4), and concentrated. Flash chromatography (SiO.sub.2, hexane:MTBE 30:1) followed by Kugelrohr distillation (bp: 70 C., 0.06 mbar) of the crude product gave 2,5-dimethylcyclopentyl (E)-but-2-enoate (2.1 g, colorless oil, 31% yield over 2 steps, mixture of isomers=20:74:6).

[0129] (2S*,5S*)-2,5-dimethylcyclopentyl (E)-but-2-enoate (cis, trans; 74%): .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm selected signals 6.95 (dq, J=15.4, 6.9 Hz, 1H) 5.85 (dq, J=15.4, 1.8 Hz, 1H) 4.71 (dd, J=4.3, 6.1 Hz, 1H) 1.87 (dd, J=1.8, 6.8 Hz, Me) 1.02 (d, J=7.1 Hz, Me), 0.90 (d, J=6.8 Hz, Me). .sup.13C-NMR (100 MHz, CDCl.sub.3) ppm 166.5 (s) 143.9 (d) 123.1 (d) 83.9 (d) 39.4 (d) 36.1 (d) 31.7 (t) 31.1 (t) 19.2 (q) 17.9 (q) 14.3 (q). GC/MS (EI): 182 (M.sup.+, <1), 167 (<1), 153 (<1), 113 (2), 96 (21), 81 (20), 69 (100), 55 (11), 41 (16).

[0130] (1s*,2R*,5S*)-2,5-dimethylcyclopentyl (E)-but-2-enoate (cis, cis; 6%): .sup.1H-NMR (600 MHz, BENZENE-d.sub.6) ppm 6.95 (dq, J=15.4, 6.8 Hz, 1H) 5.83 (d, J=15.4 Hz, 1H) 5.37 (t, J=4.1 Hz, 1H) 1.80-1.88 (m, 2H) 1.57-1.77 (m, 2H) 1.39-1.46 (m, 2H) 1.33 (d, J=6.8 Hz, 3H) 0.98 (d, J=6.8 Hz, 6H). .sup.13C NMR (150 MHz, BENZENE-d.sub.6) ppm 165.9 (s) 143.7 (d) 123.3 (d) 80.3 (d) 39.3 (d, 2C) 31.3 (t, 2C) 17.5 (q) 14.9 (q, 2C). GC/MS (EI): 113 (M.sup.+C.sub.4H5O, 4), 96 (20), 81 (18), 69 (100), 55 (12), 41 (20).

[0131] (1r*,2R*,5S*)-2,5-dimethylcyclopentyl (E)-but-2-enoate (trans, trans; 20%): .sup.1H-NMR (600 MHz, BENZENE-d.sub.6) ppm 6.95 (dq, J=15.4, 6.8 Hz, 1H) 5.85 (br d, J=15.4 Hz, 1H) 4.71 (t, J=7.2 Hz, 1H) 2.04-1.97 (m, 2H) 1.64-1.71 (m, 2H) 1.33 (br d, J=6.8 Hz, 3H) 1.04 (d, J=7.2 Hz, 6H). .sup.13C NMR (101 MHz, CDCl.sub.3) ppm 166.2 (s) 143.9 (d) 123.5 (d) 86.9 (d) 40.5 (d, 2C) 30.4 (t, 2C) 18.5 (q, 2C) 17.5 (q). GC/MS (EI): 113 (M.sup.+C.sub.4H5O, 4), 96 (20), 82 (18), 69 (100), 55 (12), 41 (20). GC/MS (EI): 113 (M.sup.+C.sub.4H.sub.5O, 3), 96 (26), 81 (27), 69 (100), 55 (11), 41 (18).

[0132] Odor of the mixture of isomers (20:74:6): fruity, damascone-like, plum; the odor of the all-syn isomer (6% of the mixture) was evaluated by GC-Sniff: fruity, natural, apple, damascone-like.

Example 9: rac-(1s*,2R*,6S*)-2,6-dimethylcyclohexyl 3-(decylthio)butanoate

[0133] ##STR00016##

[0134] To the solution of 1-dodecanethiol (9.8 g, 48.4 mmol, 0.95 equiv.) and (1s*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-but-2-enoate (10.0 g, 51.0 mmol 1.0 equiv.) in THF (100 mL) was added dropwise the solution of DBU (1,8-DiazabicycloUndec-7-ene, 7.76 g, 51.0 mmol, 1.0 equiv.) in THF (50 mL). The resulting mixture was stirred during 22 h at RT, then poured on icecold 2 M aq. HCl-solution (100 mL). The product was extracted with MTBE and the organic layer washed with water and brine and dried over MgSO.sub.4. The crude product obtained after removal of the solvents was purified by flash chromatography on SiO.sub.2 (hexane/MTBE 100:1) to yield rac-(1s*,2R*,6S*)-2,6-dimethylcyclohexyl 3-(decylthio)butanoate (colourless oil, 9.87 g, 49%).

[0135] .sup.1H-NMR (400 MHz, CDCl.sub.3) ppm 0.83-0.92 (series of s, 9H), 1.19-1.25 (m, 3H), 1.27 (br. s, 12H), 1.29-1.34 (m, 7H), 1.36 (d, J=6.6 Hz, 3H), 1.38-1.46 (m, 1H), 1.54-1.69 (m, 4H), 1.70-1.78 (m, 1H), 2.44-2.52 (m, 1H), 2.54-2.59 (m, 2H), 2.67-2.74 (m, 1H), 3.16-3.32 (m, 1H), 5.07 (s, 1H). .sup.13C-NMR (101 MHz, CDCl.sub.3) ppm 14.12 (q), 18.44 (2q), 21.51 (q), 22.69 (t), 25.75 (2 t), 28.56 (t), 29.03 (t), 29.25 (t), 29.35 (t), 29.53 (t), 29.60 (t), 29.64 (t), 29.65 (t), 29.69 (t), 30.67 (t), 31.92 (t), 36.06 (d), 36.23 (d), 36.26 (d), 42.50 (t), 76.92 (d), 171.58 (s). EI-MS (70 ev). 398 (M+, 6), 287 (33), 229 (14), 201 (100), 111 (48), 87 (9), 69 (49), 55 (26), 41 (19).

Example 10: Selective Stability to Enzymatic Hydrolysis of Compounds of Examples 1-3

[0136] Enzymes of the nasal cavity are not easily available, but the nasal cavity contains similar enzymatic activities as found in the liver, namely carboxylesterases (J. L. Lewis, K. J. Nikula, R. Novak, A. R. Dahl, Anat Rec 1994, 239). Therefore the different compounds of examples 1-3 were compared for enzymatic hydrolysis using human liver microsomes. Chemicals were dissolved to a final concentration of 100 M in a total volume of 600 l of phosphate buffer (100 mM, pH 7.4, containing 1.15% potassium chloride and 1 mM of EDTA). S9 fractions from humans at a final level of 0.166 mg/ml were added (Corning Gentest Human Liver S9 Pooled Donors, 20 mg/mL protein content, Product #452961;), Lot 22877,). As control experiment, equal levels of heat inactivated S9 fractions (incubated for 10 min at 99 C.) were added to parallel samples. The samples were incubated for different time periods and then mixed in 2 ml glass vials with 300 l of Methyl-tert-butylether (MTBE) containing as internal standard 1 ppm of dodecane. Samples were extracted on a vortex mixer for 20 s, and then ca. 200 l of the supernatant was transferred to conical GC vials and concentrated under a stream of nitrogen. 1 l of these concentrated extracts were then injected with a splitless injection into an Agilent GC 6890N gas chromatograph equipped with a flame-ionisation detector. The following GC conditions were applied: Column: Rtx 5; 30 m length0.32 mm internal diameter0.25 m film thickness; Carrier gas: Hydrogen; Column flow: 2 mL; Initial temperature of 60 C. held for 2 min, subsequent linear gradient with 10 C. per minute up to a temperature of 240 C. The peak of the test compound (parent) and the peak of potentially released alcohols after ester hydrolysis were integrated and compared to synthetic reference standards. To determine calibration curves, dilutions of the test chemicals or of the potentially released alcohols were added to heat inactivated S9 fraction and extracted, concentrated and analysed as described above. All concentrations (in test samples and calibration curves) were determined by normalization to the internal standard. FIG. 1 shows the enzymatic stability in human liver S9 fractions of the compounds of example 1-3. This graph indicates both the degradation of the parent ester and the release of the corresponding alcohol, both in heat inactivated and in active S9 fractions.

[0137] For compound in Example 1, no significant cleavage (<3%) was observed, while Example 2 is completely hydrolysed by active S9 fractions and Example 3 is significantly cleaved (15%). No cleavage in heat inactivated samples was observed clearly showing that cleavage is due to enzymatic hydrolysis.

Example 11: Skin Sensitization Test of Compounds 1 and 6a in Comparison with 3-Damascone in a Cell-Based Assay

[0138] Compounds were tested using the commercial KeratinoSens assay for skin sensitization.

[0139] The KeratinoSens test compares the potential skin sensitization risk of chemicals. The KeratinoSens cell line contains a stable insertion of a Luciferase gene under the control of the ARE-element of the gene AKR1C2 and induction of luciferase is indicative of skin sensitization potential (R. Emter, G. Ellis, A. Natsch, Toxicol. Appl. Pharmacol. 2010, 245, 281-290). The assay was performed as described by the OECD test guideline 442d. KeratinoSens cells were grown for 24 h in 96-well plates. The medium was then replaced with medium containing the test chemical and the solvent dimethylsulfoxide (DMSO) at a final level of 1%. Each compound was tested at 12 binary dilutions in the range from 0.98 to 2000 M. Cells were incubated for 48 h with the test agents, and then luciferase activity and cytotoxicity were determined. This full procedure was repeated three times for each chemical. For each chemical in each repetition and at each concentration, the gene induction compared to DMSO controls and the wells with statistically significant induction over the threshold of 1.5 (i.e. 50% enhanced gene activity) were determined. Furthermore, the maximal fold-induction (Imax) and the EC1.5 value (concentration in M for induction above the threshold) were calculated. Chemicals are rated as positive (i.e. likely skin-sensitizers) in the assay if the following three criteria are fulfilled:

[0140] (i) EC1.5 value is below 1000 M.

[0141] (ii) At the lowest concentration with a gene induction above 1.5 fold, the cellular viability is above 70%.

[0142] (iii) There is an apparent overall dose-response for luciferase induction, which is similar between the repetitions.

[0143] (1s*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-but-2-enoate, the compound of Example 1, and (1S*,2S*)-2,6,6-trimethylcyclohex-3-en-1-yl (E)-but-2-enoate, the compound of Example 6a were compared with -Damascone.

[0144] FIG. 2a shows the gene-induction and cell viability curves for -Damascone and FIG. 2b the corresponding data for compound of Example 1, in which the black diamonds indicate the induction of the luciferase activity and the open squares Cellular viability, respectively.

[0145] The compound of Example 1 does not induce luciferase activity above the 1.5-fold threshold, and is thus rated as non-sensitizing by this assay. -Damascone on the other hand clearly induces the luciferase gene already at a concentration of 4.5 micromolar, indicating it is a significantly sensitizing compound. These results show that Example 1 can be used in perfume formulations for reduced sensitization risk to the consumer. Similar data have been obtained for the compound of Example 6a.

[0146] Table 1 shows the results of compounds according to this disclosure, as compared with p-Damascone. The maximal gene induction was below the threshold of 1.5-fold for the inventive compounds, while the maximal gene induction was at 29.8-fold for p-Damascone.

TABLE-US-00001 TABLE 1 Concentration for Imax (fold 1.5-fold gene Concentration for maximal gene induction 50% Cytotoxicity induction) (EC 1.5 in M) (in M) -Damascone 29.8 4.5 56.73 Compound of 1.25 No induction 86.9 Example 1 Compound of 1.13 No induction 89.4 Example 6a

Example 12: Skin Sensitization Test of Compound 1 in Comparison with Damascones in a Peptide Reactivity Assay

[0147] 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.

[0148] A peptide reactivity assay (A. Natsch, H. Gfeller, Toxicol. Sci. 2008, 106, 464-478) was conducted similarly to the DPRA assay, but including a kinetic measurement to quantify reactivity: 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 ESI(+) mode.

[0149] 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 H2O (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

[0150] Two endpoints are measured with this assay:

[0151] a) Depletion of the parent peptide (FIG. 3): The mass of the protonated parent peptide is measured and the corresponding peak integrated (% depletion). Depletion of the parent peptide is indicative of reactivity and is described as endpoint in OECD guideline 442c.

[0152] b) Formation of modified peptides (FIG. 4): 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. Peptide adduct formation is a particular sensitive endpoint to determine reactive, and thus allergenic nature of compounds.

[0153] FIGS. 3 (peptide depletion) and 4 (adduct formation on a logarithmic scale) compare the peptide reactivity of two commercial damascones with the compound of Example 1 (Example 1). After 1 h, Example 1 produces >100 lower levels of peptide adducts as compared to Damascone Delta and Damascone gamma, indicating a dramatic and unexpected reduction of reactivity (and thus allergenicity) for Example 1. Peptide depletion indicates complete consumption of the peptide by Damascones, while only <10% is consumed as compared to controls for the Example 1.

Example 13: Perfume Example 1: A Freshly Cut Ginger Root Perfume for Shampoo Application (0.5% in Shampoo Base)

[0154]

TABLE-US-00002 CAS-No. Compound/Ingredient parts by weight 150-84-5 ACET CITRONELLYLE 60 105-87-3 ACET GERANYLE SYNT 20 112-31-2 ALD C 10 DECYLIQUE 3 507-70-0 BORNEOL CRYSTALS 10 5392-40-5 CITRAL LEMAROME N 100 68917-33-9 CITRON TERPENES w/o CITRAL 100 65405-70-1 DECENAL-4-TRANS 1 8023-89-0 ELEMI ESS 30 10339-55-6 ETHYL LINALOL 40 470-82-6 EUCALYPTOL NATURAL 20 106-24-1 GERANIOL 980 120 24851-98-7 HEDIONE 300 97-54-1 ISOEUGENOL 20 78-70-6 LINALOL SYNT 100 68855-99-2 LITSEA CUBEBA ESS CHINE 15 67674-46-8 METHYL PAMPLEMOUSSE 30 121-33-5 VANILLIN @10% TEC 1 R1 F2 F3 DIPROPYLENE GLYCOL 30 0 0 Compound A 0 30 0 Compound B 0 0 30 1000 Compound A: (1s*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-but-2-enoate Compound B: mixture of (1s*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-but-2-enoate, (2R*,6R*)-2,6-dimethylcyclohexyl (E)-but-2-enoate and (1r*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-but-2-enoate in a ratio of 72:18:8.

[0155] The reference accord R1 comprising dipropylene glycol (DPG), but no compounds A or B gives a freshly cut ginger root impression, mainly through a citrus citral freshness combined with aromatic elements. Formula F2, wherein DPG is replaced by compound A, softens the sharp citral freshness with a juicy natural fruityness, damascone like character that complements nicely the accord and reinforces the natural ginger root connotation. Formula F3, wherein DPG is replaced by compound B, does also cover the sharp citral freshness, but adds a green chemical plastic and dusty connotation, which is not pleasant and natural anymore.

Example 14: Perfume Example 2: A Fruity Plum, Red Berry Perfume for Shampoo Application, (0.5% in Shampoo Base)

[0156]

TABLE-US-00003 CAS-No. Compound/Ingredient parts by weight 123-86-4 ACET BUTYLE 15 103-54-8 ACET CINNAMYLE 20 21722-83-8 ACET CYCLOHEXYLE ETHYLE 15 105-87-3 ACET GERANYLE SYNT 30 3681-71-8 ACET HEXENYLE-3-CIS 1 142-92-7 ACET HEXYLE 25 100-52-7 BENZALDEHYDE @10% TEC 6 10094-34-5 BUTYRATE DIMETHYL BENZ CARB 440 123-68-2 CAPRONATE ALLYLE 2 706-14-9 DECALACTONE GAMMA 3 106-24-1 GERANIOL 980 15 8013-90-9 IONONE BETA 30 103-60-6 ISOBUTYRATE PHENOXYETHYLE 300 78-70-6 LINALOL SYNT 30 118-71-8 MALTOL LG CRIST 1%/AB 10 7452-79-1 METHYL-2-BUTYRATE ETHYLE 3 104-67-6 PECHE PURE 10 104-61-0 PRUNOLIDE 4 5471-51-2 RASPBERRY KETONE (N112) 10 121-33-5 VANILLIN 1 R4 F5 F6 DIPROPYLENE GLYCOL 30 0 0 Compound A 0 30 0 Compound B 0 0 30 1000 Compound A: (1s*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-but-2-enoate Compound B: mixture of (1s*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-but-2-enoate, (2R*,6R*)-2,6-dimethylcyclohexyl (E)-but-2-enoate and (1r*,2R*,6S*)-2,6-dimethylcyclohexyl (E)-but-2-enoate in a ratio of 72:18:8.

[0157] The reference accord R4 comprising dipropylene glycol (DPG), but no compounds A or B represents a fruity berry combo, mainly between plum and raspberry. Formula F5, containing compound A instead of DPG, shifts the juicy pear freshness to a harmonized plum berry juiciness, having a natural and edible effect. Formula F6, wherein DPG is replaced by compound B, moderates the pear like freshness, but adds a green chemical plastic dusty character and became unpleasant and not natural.