ORGANIC COMPOUNDS AS FRAGRANCE

Abstract

Disclosed are oxa macrocyclic ketones of formula (I) possessing musky, powdery, nitro musk odor characteristics.

Claims

1. A method of providing fragrance, the method comprising adding a compound of formula (I) ##STR00004## wherein X is a divalent residue (CH2).sub.n optionally substituted with one additional methyl group, Y is divalent residue (CH2).sub.m, n is an integer selected from 3 to 12, and m is an integer selected from 3 to 12, with the proviso that the n+m is at least 13 and not greater than 15; and with the proviso that the compound of formula (I) is not oxacyclohexadecan-6-one to at least one other odorant or to a consumer product base.

2. A fragrance composition comprising a compound of formula (I) ##STR00005## wherein X is a divalent residue (CH2).sub.n optionally substituted with one additional methyl group, Y is divalent residue (CH2).sub.m, n is an integer selected from 3 to 12, and m is an integer selected from 3 to 12, with the proviso that the n+m is at least 13 and not greater than 15; and at least one other odorant.

3. A fragrance composition comprising a compound according to claim 1, wherein the compound is selected from the group consisting of 4-methyloxacyclopentadecan-6-one; 3-methyloxacyclopentadecan-5-one; oxacyclopentadecan-5-one; oxacyclopentadecan-6-one; oxacyclopentadecan-7-one; oxacyclopentadecan-8-one; 3-methyloxacyclohexadecan-5-one; 4-methyloxacyclohexadecan-6-one; oxacyclohexadecan-5-one; oxacyclohexadecan-7-one; oxacyclohexadecan-8-one; oxacycloheptadecan-5-one; oxacycloheptadecan-6-one; oxacycloheptadecan-7-one; oxacycloheptadecan-8-one; oxacycloheptadecan-9-one and combinations thereof.

4. A fragranced article comprising a) as odorant a compound of formula (I) ##STR00006## wherein X is a divalent residue (CH2) optionally substituted with one additional methyl group, Y is divalent residue (CH2).sub.m, n is an integer selected from 3 to 12, and m is an integer selected from 3 to 12, with the proviso that the n+m is at least 13 and not greater than 15; and b) a consumer product base.

5. The fragranced article according to claim 4 wherein the consumer product base is selected from fine perfumery, personal care products and fabric care products.

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

7. A compound of formula (I) ##STR00007## wherein X is a divalent residue (CH2).sub.n optionally substituted with one additional methyl group, Y is divalent residue (CH2).sub.m, n is an integer selected from 3 to 7, and m is an integer selected from 8 to 11, with the proviso that the n+m is at least 13 and not greater than 15; and with the proviso that oxacyclohexadecan-6-one and oxacyclohexadecan-5-one are excluded.

8. A compound according to claim 6 selected from the group consisting of 4-methyloxacyclopentadecan-6-one; 3-methyloxacyclopentadecan-5-one; oxacyclopentadecan-5-one; oxacyclopentadecan-6-one; oxacyclopentadecan-7-one; oxacyclopentadecan-8-one; 3-methyloxacyclohexadecan-5-one; 4-methyloxacyclohexadecan-6-one; oxacyclohexadecan-7-one; oxacyclohexadecan-8-one; oxacycloheptadecan-5-one; oxacycloheptadecan-6-one; oxacycloheptadecan-7-one; oxacycloheptadecan-8-one; oxacycloheptadecan-9-one, and combinations thereof.

9. The method according to claim 1, wherein X is a divalent residue (CH2).sub.n substituted with one additional methyl group, Y is divalent residue (CH2).sub.m, n is an integer selected from 3 and 4, and m is an integer selected from 9 to 11, with the proviso that the n+m is at least 13 and not greater than 15.

10. The method according to claim 1, wherein X is a divalent residue (CH2).sub.n, Y is divalent residue (CH2).sub.m, n is an integer selected from 3 to 7, and m is an integer selected from 7 to 12, with the proviso that the n+m is at least 13 and not greater than 15; and with the proviso that the compound of formula (I) is not oxacyclohexadecan-6-one.

11. The method according to claim 1, wherein X is a divalent residue (CH2).sub.n, Y is divalent residue (CH2).sub.m, n is an integer selected from 6, 7 and 8, and m is an integer selected from 6, 7 and 8, with the proviso that n+m is at least 13 and not greater than 15.

12. The method according to claim 1, wherein X is a divalent residue (CH2).sub.n, Y is divalent residue (CH2).sub.m, n is an integer selected from 6 and 7, and m is an integer selected from 6 to 9, with the proviso that n+m is at least 13 and not greater than 15.

13. The method according to claim 1, wherein the compound of formula (I) is selected from the group consisting of 4-methyloxacyclopentadecan-6-one; 3-methyloxacyclopentadecan-5-one; oxacyclopentadecan-5-one; oxacyclopentadecan-6-one; oxacyclopentadecan-7-one; oxacyclopentadecan-8-one; 3-methyloxacyclohexadecan-5-one; 4-methyloxacyclohexadecan-6-one; oxacyclohexadecan-5-one; oxacyclohexadecan-7-one; oxacyclohexadecan-8-one; oxacycloheptadecan-5-one; oxacycloheptadecan-6-one; oxacycloheptadecan-7-one; oxacycloheptadecan-8-one; oxacycloheptadecan-9-one, and combinations thereof.

Description

Example 1: 4-methyloxacyclohexadecan-6-one

[0090] Example 1a: 10-((3-methylbut-3-en-1-yl)oxy)dec-1-ene: A suspension of sodium hydride (0.65 g, 60 wt % in mineral oil, 16.2 mmol) in tetrahydrofuran (THF) (30 mL) was treated slowly at room temperature (r.t.) with a solution of 3-methylbut-3-en-1-ol (1.20 g, 1.41 mL, 97 wt %, 13.5 mmol) in THF (10 mL). After addition the mixture was heated to 60 C. and stirred for 1 h and then treated with 10-bromodec-1-ene (3.55 g, 16.2 mmol) and the resulting mixture stirred at 60 C. overnight. After cooling to r.t., the mixture was poured onto iced water (50 mL), extracted with MTBE (methyl tert-butyl ether) (280 mL), washed with water (80 mL) and brine (50 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated. The resulting material was purified by flash column chromatography on silica gel, eluting with a gradient of MTBE in heptane to give 10-((3-methylbut-3-en-1-yl)oxy)dec-1-ene (1.6 g, 7.13 mmol, 53% yield) as a yellow liquid.

[0091] 1H NMR (400 MHz, CDCl3, 298 K) (ppm)=5.83 (tdd, J=6.6, 10.3, 17.1 Hz, 1H), 5.01 (qd, J=1.8, 17.1 Hz, 1H), 4.95 (tdd, J=1.2, 2.3, 10.2 Hz, 1H), 4.82-4.72 (m, 2H), 3.54 (t, J=7.1 Hz, 2H), 3.44 (t, J=6.7 Hz, 2H), 2.32 (t, J=7.0 Hz, 2H), 2.10-2.02 (m, 2H), 1.77 (s, 3H), 1.59 (quin, J=7.0 Hz, 2H), 1.45-1.26 (m, 10H).

[0092] 13C NMR (101 MHz, CDCl3, 298 K) (ppm)=143.0, 139.2, 114.1, 111.3, 71.0, 69.3, 37.8, 33.8, 29.7, 29.4, 29.4, 29.1, 28.9, 26.2, 22.8.

[0093] GC/MS (El, 70 eV): 209 (2, [M-CH.sub.3].sup.+), 169 (1), 155 (1), 109 (9), 99 (36), 83 (74), 70 (100), 69 (63), 55 (95).

[0094] Example 1b: methyl 11-((5-methoxy-3-methyl-5-oxopentyl)oxy)undecanoate: In an autoclave, a solution of 10-((3-methylbut-3-en-1-yl)oxy)dec-1-ene (1.60 g, 7.13 mmol) in Methanol (15 mL) was treated with Bis(acetonitrile)dichloropalladium(II) (93.4 mg, 99 wt %, 357 mol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphane) (213 mg, 97 wt %, 357 mol) and methanesulfonic acid (69.2 mg, 99 wt %, 713 mol) and the resulting mixture flushed with carbon monoxide (CO) then pressurized with CO to 15 bar and heated to 80 C. for 20 h. The mixture was then cooled to r.t., the gas pressure was released carefully and the mixture poured into iced water (100 mL), extracted with EtOAc (ethyl acetate) (250 mL), washed with water (50 mL), brine (50 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated. The resulting material was purified by flash column chromatography on silica gel, eluting with a gradient of MTBE in heptane to give methyl 11-((5-methoxy-3-methyl-5-oxopentyl)oxy)undecanoate (1.40 g, 3.43 mmol, 48% yield) along with other regioisomers, as a pale yellow oil which was used in the following step without further purification.

[0095] GC/MS (El, 70 eV): 344 (1, [M].sup.+*), 312 (1), 280 (2), 271 (2), 215 (12), 199 (4), 183 (20), 145 (61), 129 (75), 113 (100) 101 (22), 97 (25), 87 (49), 69 (66), 59 (21), 55 (41), 41 (25).

[0096] Example 1c: mixture of methyl 4-methyl-6-oxooxacyclohexadecane-7-carboxylate and methyl 4-methyl-6-oxooxacyclohexadecane-5-carboxylate: A solution of methyl 11-((5-methoxy-3-methyl-5-oxopentyl)oxy)undecanoate (1.40 g, 4.06 mmol) in THF (180 ml) was added dropwise over 6.5 h to a refluxing mixture of NaHMDS (sodium hexamethyldisilazide) (8.94 g, 24.4 mL, 2.0 molar in THF, 48.8 mmol) and THF (120 ml). The reaction was then further refluxed for additional 30 min then cooled to r.t. and slowly treated with acetic acid (AcOH) (20 mL). The mixture was then washed with water (3150 mL) and the washings extracted with MTBE (200 mL). the combined organic layers were washed with brine (150 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated. The resulting material was purified by flash column chromatography on silica gel, eluting with a gradient of MTBE in heptane to give a mixture of methyl 4-methyl-6-oxooxacyclohexadecane-7-carboxylate and methyl 4-methyl-6-oxooxacyclohexadecane-5-carboxylate (0.190 g, 89% purity, 13% yield) which was taken to the next step without further purification.

[0097] GC/MS (El, 70 eV): 312 (1, [M].sup.+*), 281 (3), 170 (5), 115 (100).

[0098] Example 1d: 4-methyloxacyclohexadecan-6-one: A solution of mixture of methyl 4-methyl-6-oxooxacyclohexadecane-7-carboxylate and methyl 4-methyl-6-oxooxacyclohexadecane-5-carboxylate (0.17 g, 0.54 mmol) in MeOH (5 ml) was treated with aqueous NaOH (0.82 mL, 2 molar, 1.6 mmol) and the resulting mixture heated to reflux (80 C.) for 1 h. The resulting mixture was then cooled to r.t., acidified to pH 1 by dropwise addition of 10% H.sub.2SO.sub.4 and then heated to reflux for 30 min. The mixture was then cooled to r.t., extracted with MTBE (250 mL), washed with water (50 mL), brine (50 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated. The resulting material was purified by flash column chromatography on silica gel, eluting with a gradient of MTBE in heptane to give 4-methyloxacyclohexadecan-6-one (0.100 g, 98% purity, 0.54 mmol, 71% yield) as a colorless liquid.

[0099] 1H NMR (400 MHz, CDCl3, 298 K) (ppm)=3.53-3.35 (m, 4H), 2.57 (dd, J=5.9, 14.1 Hz, 1H), 2.49-2.35 (m, 2H), 2.34-2.21 (m, 1H), 2.20-2.11 (m, 1H), 1.76-1.21 (m, 18H), 0.93 (d, J=6.6 Hz, 3H).

[0100] 13C NMR (101 MHz, CDCl3, 298 K) (ppm)=212.2, 70.3, 68.0, 50.7, 40.7, 36.6, 29.1, 27.1, 27.0, 26.9, 26.8, 25.9, 25.8, 25.0, 22.4, 20.0.

[0101] GC/MS (El, 70 eV): 254 (6, [M]+*), 239 (1), 167 (4), 149 (6), 125 (37), 115 (63), 97 (100), 83 (26), 69 (53), 55 (63), 41 (54).

[0102] Odour description (10% solution in DPG on paper blotter, 4 h): musky, powdery, ambery, nitro musk.

Example 2: oxacyclopentadecan-6-one

[0103] Example 2a: methyl 10-((5-methoxy-5-oxopentyl)oxy)decanoate: A mixture of 1,7-dioxacycloheptadecan-8-one (58.33 g, 228 mmol) and NaOH (10.94 g, 273 mmol) in water (100 mL) was refluxed for 4 hours. After the total conversion of the starting lactone (monitoring with GC and TLC), the mixture was cooled to room temperature, then diluted HCl was added dropwise to obtain pH=6-7. The mixture was then cooled to 0 C., then KMnO.sub.4 (43.20 g, 273 mmol) was added in portions to the reaction mixture at 0 C. and the resulting mixture stirred overnight at room temperature. The mixture was then filtered and the filtrate treated dropwise with 2M HCl to obtain pH=4-5 with concomitant formation of a white precipitate. The precipitate was filtered to give crude diacid (70.01 g) as a white solid. The solid was mixed with methanol (100 mL) and treated with 2 drops of conc. sulfuric acid. The reaction mixture was stirred at reflux for 2 hours then cooled to room temperature. The solvent was evaporated and the resulting oil purified by column chromatography on silica gel, eluting with a gradient of MTBE in heptane to give methyl 10-((5-methoxy-5-oxopentyl)oxy)decanoate (19.37 g, 61 mmol, 27% yield) as a colorless oil.

[0104] 1H NMR (400 MHz, CDCl3) (ppm)=3.68, 3.66 (s, 6H), 3.52-3.20 (m, 4H), 2.37-2.25 (m, 4H), 1.81-1.42 (m, 8H), 1.38-1.22 (m, 10H).

[0105] 13C NMR (101 MHz, CDCl3) (ppm)=174.23 (s), 173.99 (s), 70.96 (t), 70.23 (t), 51.40 (q), 51.36 (q), 34.05 (t), 33.78 (t), 29.70 (t), 29.37 (t), 29.33 (t), 29.14 (t), 29.08 (t), 26.12 (t), 24.90 (t), 21.75 (t).

[0106] GC/MS (El): m/z (%): 284 (1) [M+], 252 (4), 201 (17), 169 (42), 131 (77), 115 (94), 101 (86), 99 (97), 83 (65), 73 (50), 55 (100).

[0107] Example 2b: mixture of methyl 6-oxooxacyclopentadecane-7-carboxylate and methyl 6-oxooxacyclopentadecane-5-carboxylate: A solution of methyl 10-((5-methoxy-5-oxopentyl)oxy)decanoate (6.00 g, 17 mmol) in THF (340 mL) was slowly added at a speed of 50 mL/h to a refluxing mixture of LiHMDS (Lithium hexamethyldisilazide) (180 mL, 1M in THF, 180 mmol) and THF (220 mL) under Argon. After completion of the feed, the mixture was further stirred for 15 min at reflux. The mixture was then cooled to room temperature and treated with diluted HCl to obtain a pH=4-5, extracted with MTBE (3200 mL), washed with water (200 mL), brine (200 mL), dried over MgSO.sub.4 and concentrated. The obtained crude oil was purified by column chromatography on silica gel, eluting with a gradient of MTBE in heptane to give a mixture of methyl 6-oxooxacyclopentadecane-7-carboxylate and methyl 6-oxooxacyclopentadecane-5-carboxylate (2.30 g, 8.1 mmol, 43% yield, Ratio of two isomers=1.3:1) as a light yellow oil.

[0108] 1H NMR (400 MHz, CDCl3) (ppm)=3.71 (s, 3H), 3.66-3.57 (m, 1H), 3.54-3.30 (m, 4H), 2.82-2.43 (m, 2H), 2.18-1.86 (m, 2H), 1.85-1.68 (m, 3H), 1.64-1.51 (m, 4H), 1.42-1.28 (m, 9H).

[0109] 13C NMR (101 MHz, CDCl3) (ppm)=207.05 (s), 206.58 (s), 170.34 (s), 170.25 (s), 70.57 (t), 70.33 (t), 70.21 (t), 69.81 (t), 58.40 (d), 57.23 (d), 52.26 (q), 52.22 (q), 42.87 (t), 40.51 (t), 28.92 (t), 28.80 (t), 28.37 (t), 28.09 (t), 27.53 (t), 27.19 (t), 27.00 (t), 26.98 (t), 26.74 (t), 26.41 (t), 26.17 (t), 25.54 (t), 25.40 (t), 25.30 (t), 25.12 (t), 23.23 (t), 21.64 (t).

[0110] Major GC/MS (El): m/z (%): 284 (1) [M+], 253 (5), 207 (6), 156 (10), 115 (33), 100 (73), 83 (33), 69 (38), 55 (100)., Minor GC/MS (El): m/z (%): 284 (1) [M+], 253 (3), 207 (1), 156 (10), 110 (9), 101 (100), 83 (36), 69 (16), 55 (65).

[0111] Example 2c: oxacyclopentadecan-6-one: A mixture of methyl 6-oxooxacyclopentadecane-7-carboxylate and methyl 6-oxooxacyclopentadecane-5-carboxylate (2.50 g, 8 mmol) was dissolved in MeOH (100 mL) and treated with a solution of NaOH (0.96 g, 24 mmol) in water (100 mL) at room temperature, and the resulting mixture was refluxed for 1 h. After cooling down, the mixture was acidified to pH=3-4 with 10% H.sub.2SO.sub.4, followed by refluxing for 30 min.

[0112] The mixture was then cooled to room temperature and concentrated under reduced pressure to remove MeOH. The residue was extracted with MTBE (3100 mL), washed with water (100 mL), brine (100 mL), dried over MgSO.sub.4 and concentrated. The resulting material was purified by column chromatography on silica gel, eluting with a gradient of MTBE in heptane, followed by Kugelrohr distillation (190 C., 0.082 MPa) to give oxacyclopentadecan-6-one (1.76 g, 7.4 mmol, 92% yield) as a colorless oil. 1H NMR (400 MHz, CDCl3) (ppm)=3.49-3.36 (m, 4H), 2.58-2.48 (m, 2H), 2.47-2.37 (m, 2H), 1.79-1.63 (m, 4H), 1.60-1.48 (m, 3H), 1.47-1.20 (m, 11H).

[0113] 13C NMR (101 MHz, CDCl3) (ppm)=213.12 (s), 70.49 (t), 70.18 (t), 43.12 (t), 41.45 (t), 28.97 (t), 28.78 (t), 27.31 (t), 27.05 (t), 26.58 (t), 26.29 (t), 25.12 (t), 24.08 (t), 21.96 (t).

[0114] GC/MS (El): m/z (%): 226 (8) [M+], 135 (7), 111 (26), 101 (55), 98 (90), 83 (75), 81 (20), 69 (30), 55 (100).

[0115] Odour description (10% solution in DPG on paper blotter, 4 h): musky, powdery, nitro musk.

Example 3: oxacyclohexadecan-9-one

[0116] Example 3a: 8-(benzyloxy)octyl 4-methylbenzenesulfonate: A flask was charged with 8-(benzyloxy)octan-1-ol (10.0 g, 42.3 mmol), Dichloromethane (100 mL), Et.sub.3N (trimethylamine) (5.19 g, 7.15 mL, 50.8 mmol) and the reaction mixture was cooled to 0 C. (ice bath). Finally, p-toluenesulfonyl chloride (9.78 g, 50.8 mmol) was added in small portions over 30 min, the reaction mixture was stirred at 0 C. for 30 min and then stirred for 17 h (overnight) at rt. The reaction mixture was poured into ice-cold HCl 1M (150 ml) and stirred vigorously for 10 min.

[0117] The mixture was extracted with MTBE (2150 ml), washed with sat. NaHCO.sub.3 solution (1150 ml) and brine (1100 ml), dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure to give 8-(benzyloxy)octyl 4-methylbenzenesulfonate (17.7 g, 94% purity, 42.5 mmol, quant. yield) as a yellow oil which was used without further purification.

[0118] GC/MS (El, 70 eV): 390 (1, [M].sup.+*), 372 (1), 218 (1), 173 (33), 155 (6), 107 (37), 91 (100).

[0119] Example 3b: (((oxybis(octane-8,1-diyl))bis(oxy))bis(methylene))dibenzene: A suspension of sodium hydride (2.5 g, 60 wt % in mineral oil, 62.2 mmol) in THF (100 ml) was treated at r.t. with a solution of 8-(benzyloxy)octan-1-ol (14.0 g, 59.2 mmol) in THF (50 ml) over 30 min and the resulting reaction mixture heated to 60 C. for 1 h. Finally, a solution of 8-(benzyloxy)octyl 4-methylbenzenesulfonate (24.3 g, 62.2 mmol) in THF (50 ml) was added over 45 min. The reaction mixture was stirred at r.t. for 17 h then at 60 C. for 23 h. The reaction mixture was poured into ice water (200 ml) and stirred vigorously for 10 min. The mixture was then extracted with MTBE (2200 ml), the org. layers were washed with water (1200 ml) and brine (1150 ml). The combined org. layers were dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure to give a product that was purified by column chromatography on silica gel, eluting with a gradient of MTBE in heptane to give (((oxybis(octane-8,1-diyl))bis(oxy))bis(methylene))dibenzene (19.0 g, 41.8 mmol, 71% yield) as a colorless oil.

[0120] 1H NMR (400 MHz, CDCl3, 298 K) (ppm)=7.37-7.30 (m, 8H), 7.30-7.23 (m, 2H), 4.49 (s, 4H), 3.45 (t, J=6.6 Hz, 4H), 3.38 (t, J=6.7 Hz, 4H), 1.65-1.50 (m, 8H), 1.40-1.26 (m, 16H).

[0121] 13C NMR (101 MHz, CDCl3, 298 K) (ppm)=138.7, 128.3, 127.6, 127.5, 72.9, 71.0, 70.5, 29.8, 29.5, 26.2.

[0122] GC/MS (El, 70 eV): 363 (5, [M-CH.sub.2Ph].sup.+*), 235 (1), 111 (13), 167 (9), 91 (100).

[0123] Example 3c: 8,8-oxybis(octan-1-ol): A solution of (((oxybis(octane-8,1-diyl))bis(oxy))bis(methylene))dibenzene (19.0 g, 41.8 mmol) in Methanol (250 mL) was treated with palladium on carbon (2.22 g, 10 wt % palladium, 2.09 mmol). The flask was placed under vacuum and purged with argon and then flushed with hydrogen gas to expel the argon. The mixture was stirred at rt under H.sub.2-atmosphere (Balloon-pressure) for 20 h then flushed with argon gas to expel the hydrogen. The mixture was filtered over a short pad of silica, washing with EtOAc (2100 ml) and the filtrate was concentrated under reduced pressure to give 8,8-oxybis(octan-1-ol) (11.05 g, 40.2 mmol, 96% yield) as a beige solid.

[0124] 1H NMR (400 MHz, CDCl3, 298 K) (ppm)=3.62 (t, J=6.7 Hz, 4H), 3.39 (t, J=6.7 Hz, 4H), 1.95 (br s, 2H), 1.64-1.48 (m, 8H), 1.41-1.26 (m, 16H).

[0125] 13C NMR (101 MHz, CDCl3, 298 K) (ppm)=70.9, 62.9, 32.7, 29.7, 29.4, 29.4, 26.1, 25.7. GC/MS (El, 70 eV): 256 (1, [M-H.sub.2O].sup.+*), 145 (17), 129 (6), 127 (14), 109 (46), 69 (100).

[0126] Example 3d: 8,8-oxydioctanoic acid: A solution of 8,8-oxybis(octan-1-ol) (10.0 g, 36.4 mmol) in Acetone (200 mL) was treated dropwise at r.t. (water bath cooling) with Jones reagent (67 g, 52 mL, 36.4 mmol) over 60 min until the reaction mixture showed a persistent orange color. After stirring for 2 h at r.t., the reaction mixture was quenched with isopropanol (50 ml).

[0127] The reaction mixture was poured into ice cold NaOH 2M (150 ml) and stirred vigorously for 10 min. The mixture was extracted with EtOAc (1150 ml) and the org. layer was discarded.

[0128] The aq. layer was then acidified with HCl 5 M to pH 1, filtered, extracted with CH.sub.2Cl.sub.2 (2200 ml) and the org. layers were washed with brine (1150 ml). The combined org. layers were dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure to give 8,8-oxydioctanoic acid (9.40 g, 80% purity, 25 mmol, 69% yield) as a white solid which was used without further purification.

[0129] 1H NMR (400 MHz, CDCl3, 298 K) (ppm)=10.29 (br s, 2H), 3.40 (t, J=6.7 Hz, 4H), 2.34 (t, J=7.5 Hz, 4H), 1.72-1.49 (m, 8H), 1.44-1.23 (m, 12H).

[0130] 13C NMR (101 MHz, CDCl3, 298 K) (ppm)=180.1, 70.8, 34.1, 29.6, 29.0, 29.0, 26.0, 24.6.

[0131] Example 3e: dimethyl 8,8-oxydioctanoate: A mixture of 8,8-oxydioctanoic acid (9.40 g, 31.1 mmol), Methanol (200 mL) and 1 drop of sulfuric acid (311 mg, 0.169 mL, 3.11 mmol) was heated to 65 C. and stirred for 3.5 h. The reaction mixture was poured into ice water (200 ml) and stirred vigorously for 10 min. The mixture was extracted with MTBE (2150 ml), the org. layers were washed with water (1150 ml), aqueous saturated NaHCO.sub.3 solution (1100 ml) and brine (1100 ml). The combined org. layers were dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure to give dimethyl 8,8-oxydioctanoate (9.40 g, 95% purity, 29.2 mmol, 94% yield) as a pale yellow liquid.

[0132] 1H NMR (400 MHz, CDCl3, 298 K) (ppm)=3.66 (s, 6H), 3.38 (t, J=6.7 Hz, 4H), 2.30 (t, J=7.5 Hz, 4H), 1.70-1.49 (m, 8H), 1.40-1.26 (m, 12H).

[0133] 13C NMR (101 MHz, CDCl3, 298 K) (ppm)=174.2, 70.9, 51.4, 34.0, 29.7, 29.1, 29.1, 26.0, 24.9.

[0134] GC/MS (El, 70 eV): 299 (1, [M-MeO].sup.+*), 281 (1), 267 (1), 257 (3), 173 (48), 157 (26), 141 (100), 125 (80), 59 (19), 55 (69).

[0135] Example 3f: methyl 9-oxooxacyclohexadecane-8-carboxylate: A solution of dimethyl 8,8-oxydioctanoate (5.00 g, 15.1 mmol) in THF (270 ml) was added over 6 h under N.sub.2 atmosphere to a gently refluxing mixture of NaHMDS (27.7 g, 75.6 mL, 2.0 molar in THF, 151 mmol) and THF (450 ml). After the addition the reaction mixture was refluxed for an additional 1 h then cooled to r.t. and treated slowly with acetic acid (50 ml). The reaction mixture was washed with water (2250 ml) and the water layers were extracted with MTBE (250 ml). The org. layers were finally washed with brine (1200 ml), dried over Na.sub.2SO.sub.4, filtered and concentrated under reduced pressure. The resulting material was purified by column chromatography on silica gel, eluting with a gradient of MTBE in heptane to give methyl 9-oxooxacyclohexadecane-8-carboxylate (1.60 g, 96% purity, 4.90 mmol, 32% yield) as a pale yellow liquid.

[0136] 1H NMR (400 MHz, CDCl3, 298 K) (ppm)=3.77-3.65 (m, 3H), 3.57 (dd, J=6.5, 8.4 Hz, 1H), 3.51-3.35 (m, 4H), 2.64-2.47 (m, 2H), 2.05-1.79 (m, 2H), 1.78-1.19 (m, 18H).

[0137] 13C NMR (101 MHz, CDCl3, 298 K) (ppm)=206.6, 170.2, 69.4, 69.4, 57.6, 52.2, 40.7, 29.0, 28.9, 27.8, 27.6, 27.5, 27.3, 26.6, 25.5, 25.4, 22.8.

[0138] GC/MS (El, 70 eV): 298 (2, [M]+*), 283 (1), 280 (1), 267 (9), 248 (2), 238 (1), 125 (58), 98 (46), 87 (34), 55 (100), 41 (37).

[0139] Example 3g: oxacyclohexadecan-9-one: A solution of methyl 9-oxooxacyclohexadecane-8-carboxylate (1.6 g, 5.4 mmol) in MeOH (50 ml) was treated with aqueous NaOH (0.64 g, 8.0 mL, 2 molar, 16 mmol) and the resulting mixture heated to reflux (80 C.) for 1 h. The resulting mixture was then cooled to r.t., acidified to pH 1 by dropwise addition of 10% H.sub.2SO.sub.4 and then heated to re-flux for 30 min. The mixture was then cooled to r.t., extracted with MTBE (2100 mL), washed with water (100 mL), brine (100 mL), dried over Na.sub.2SO.sub.4, filtered and concentrated. The resulting material was purified by flash column chromatography on silica gel, eluting with a gradient of MTBE in heptane to give oxacyclohexadecan-9-one (1.0 g, 4.2 mmol, 77% yield) as a pale yellow liquid.

[0140] 1H NMR (400 MHz, CDCl3, 298 K) (ppm)=3.48-3.38 (m, 4H), 2.41 (t, J=7.2 Hz, 4H), 1.74-1.62 (m, 4H), 1.60-1.50 (m, 4H), 1.49-1.39 (m, 4H), 1.38-1.26 (m, 8H).

[0141] 13C NMR (101 MHz, CDCl3, 298 K) (ppm)=212.8, 69.4, 41.5, 29.0, 27.9, 27.3, 25.4, 23.5. GC/MS (El, 70 eV): 240 (5, [M].sup.+*), 225 (1), 197 (1), 153 (11), 125 (45), 97 (45), 82 (58), 55 (100), 41 (54), 29 (15).

[0142] Odour description (10% solution in DPG on paper blotter, 4 h): musky, powdery, nitro musk, warm.

Example 4a to 4e

[0143] Following the general procedure described in Example 3, the compounds 4a-4e were prepared.

[0144] 4a: oxacyclohexadecan-8-one: using 9-(phenylmethoxy)-1-nonanol in the first step (Tosylation), then reacting it with 7-(phenylmethoxy)-1-heptanol, followed by the steps described. This gave oxacyclohexadecan-8-one as a pale yellow oil.

[0145] .sup.1H NMR (400 MHz, CDCl.sub.3) (ppm)=3.44-3.23 (m, 4H), 2.52-2.18 (m, 4H), 1.72-1.52 (m, 4H), 1.52-1.39 (m, 4H), 1.38-1.15 (m, 12H).

[0146] .sup.13C NMR (101 MHz, CDCl.sub.3) (ppm)=211.59 (q), 68.99 (t), 68.64 (t), 41.02 (t), 40.64 (t), 28.30 (t), 27.96 (t), 27.08 (t), 26.51 (t), 26.21 (t), 26.09 (t), 25.03 (t), 24.04 (t), 22.64 (t), 22.36 (t). GC/MS (El): m/z (%): 240 (5) [M+], 139 (17), 126 (18), 111 (28), 97 (26), 83 (33), 81 (25), 69 (45), 55 (100).

[0147] Odour description (10% solution in DPG on paper blotter, 4 h): musky, powdery, nitro musk, warm.

[0148] 4b: oxacycloheptadecan-7-one: using 6-(benzyloxy)-1-hexanol in the first step (Tosylation), then reacting it with 11-(phenylmethoxy)-1-undecanol, followed by the steps described. This gave oxacycloheptadecan-7-one as a colorless liquid.

[0149] .sup.1H NMR (500 MHz, CDCl3, 298 K) (ppm)=3.45-3.37 (m, 4H), 2.43 (t, J=6.7 Hz, 2H), 2.40 (t, J=6.9 Hz, 2H), 1.68-1.59 (m, 4H), 1.58-1.49 (m, 4H), 1.45-1.35 (m, 4H), 1.35-1.23 (m, 10H).

[0150] .sup.13C NMR (126 MHz, CDCl3, 298 K) (ppm)=212.4, 70.3, 70.2, 42.5, 42.5, 29.8, 29.2, 27.9, 27.9, 27.5, 27.2, 27.1, 26.6, 25.6, 24.1, 23.3.

[0151] GC/MS (El, 70 eV): 254 (5, [M]+*), 236 (1), 211 (1), 125 (23), 112 (26), 97 (35), 83 (21), 69 (48), 55 (100), 41 (70).

[0152] Odour description (10% solution in DPG on paper blotter, 4 h): musky, powdery, nitro musk, slightly ambery.

[0153] 4c: oxacycloheptadecan-6-one: using 5-(Benzyloxy)-1-pentanol in the first step (Tosylation), then reacting it with 12-(Phenylmethoxy)-1-dodecanol, followed by the steps described. This gave oxacycloheptadecan-6-one as a colorless liquid.

[0154] .sup.1H NMR (500 MHz, CDCl3, 298 K) (ppm)=3.47-3.39 (m, 4H), 2.49-2.39 (m, 4H), 1.77-1.69 (m, 2H), 1.68-1.58 (m, 4H), 1.58-1.51 (m, 2H), 1.47-1.38 (m, 2H), 1.37-1.26 (m, 12H).

[0155] .sup.13C NMR (126 MHz, CDCl3, 298 K) (ppm)=212.7, 70.3, 43.1, 41.9, 29.4, 29.4, 27.6, 27.3, 27.2, 26.9, 25.5, 23.6, 22.1.

[0156] GC/MS (El, 70 eV): 254 (5, [M].sup.+*), 236 (1), 225 (1), 111 (32), 98 (82), 83 (60), 69 (22), 55 (100), 41 (65).

[0157] Odour description (10% solution in DPG on paper blotter, 4 h): musky, powdery, nitro musk, slightly ambery.

[0158] 4d: oxacycloheptadecan-9-one: using 8-(Benzyloxy)-1-octanol in the first step (Tosylation), then reacting it with 9-(Phenylmethoxy)-1-nonanol, followed by the steps described. This gave oxacycloheptadecan-9-one as a colorless liquid.

[0159] .sup.1H NMR (500 MHz, CDCl3, 298 K) (ppm)=3.46-3.37 (m, 4H), 2.47-2.35 (m, 4H), 1.70-1.59 (m, 4H), 1.58-1.50 (m, 4H), 1.47-1.38 (m, 4H), 1.38-1.22 (m, 10H).

[0160] .sup.13C NMR (126 MHz, CDCl3, 298 K) (ppm)=212.9, 70.0, 69.9, 42.9, 41.9, 29.5, 29.4, 28.7, 28.3, 28.2, 28.2, 25.8, 24.1, 23.8.

[0161] GC/MS (El, 70 eV): 254 (3, [M].sup.+*), 239 (1), 211 (1), 197 (1), 171 (2), 153 (4), 139 (9), 125 (15), 111 (14), 97 (26), 82 (24), 69 (24), 55 (100), 41 (55).

[0162] Odour description (10% solution in DPG on paper blotter, 4 h): musky, powdery, nitro musk, slightly ambery, warm.

[0163] 4e: oxacycloheptadecan-8-one: using 7-(Benzyloxy)-1-heptanol in the first step (Tosylation), then reacting it with 10-(Phenylmethoxy)-1-decanol, followed by the steps described. This gave oxacycloheptadecan-8-one as a colorless liquid.

[0164] .sup.1H NMR (500 MHz, CDCl3, 298 K) (ppm)=3.47-3.38 (m, 4H), 2.44 (t, J=6.9 Hz, 2H), 2.42-2.38 (m, 2H), 1.71-1.61 (m, 4H), 1.59-1.51 (m, 4H), 1.46-1.24 (m, 14H).

[0165] .sup.13C NMR (126 MHz, CDCl3, 298 K) (ppm)=212.4, 70.2, 70.1, 42.1, 41.9, 29.4, 29.3, 28.4, 28.1, 28.0, 27.8, 27.4, 26.0, 25.9, 23.7, 23.5.

[0166] GC/MS (El, 70 eV): 254 (4, [M]+*), 236 (1), 211 (1), 197 (2), 186 (3), 169 (2), 153 (3), 139 (9), 126 (16), 111 (22), 98 (15), 83 (24), 69 (36), 55 (100), 41 (58).

[0167] Odour description (10% solution in DPG on paper blotter, 4 h): musky, powdery, nitro musk, slightly ambery.

Example 5: Fragrance Composition

TABLE-US-00001 parts by Ingredient weight Benzyl acetate 0.6 3,7-Dimethyl-1,6-octadien-3-yl acetate 0.5 2-Methoxy-4-(1-propenyl)phenyl acetate 0.1 2-Phenylethanol 2.0 2-Hexyl-3-phenyl-2-propenal 0.3 Decanal @ 10% in TEC 0.4 Dodecanal @ 10% in TEC 0.5 Dipropylene glycol (DPG) 62.9 Cinnamaldehyde @ 10% in TEC 0.4 Ambrox 0.2 Bergamot oil 6.0 Cedarwood oil 0.1 Ethylene Brassylate 14.0 Cashmeran (6,7-dihydro-1,1,2,3,3-pentamethyl-4(5h)- 0.1 indanone Citronellol (3,7-dimethyl-6-octen-1-ol) 0.3 Coumarine pure 0.7 Gardenol (1-phenylethyl acetate) 0.1 Geraniol 0.4 Hedione (methyl 3-oxo-2-pentylcyclopentaneacetate 0.7 7-Hydroxy-3,7-dimethyloctan-1-al 2.3 Indole @ 1% in TEC 1.0 Iris absolute 0.2 Isoraldeine 2.5 cis-Jasmone (3-methyl-2-(pent-2-en-1-yl)cyclopent-2-enone) 0.1 @ 10% in DPG Linalol 0.6 Methyl 2-(methylamino)benzoate @ 10% in DPG 0.7 Methyl cedryl ketone 0.2 Nerolex (3,7-dimethyl-2,6-octadien-1-ol) 0.2 sweet orange oil 1.0 Patchouli oil 0.2 Peche Pure (4-undecanolide) @ 10% in DPG 0.2 Phenylethyl phenylacetate 0.2 Vetiver oil 0.3 100.0

[0168] By replacing 8 parts DPG with 8 parts oxacyclohexadecan-9-one (a compound of formula (I)) the fragrance composition is perceived more rounded off, better blended, warmer with a musky note, adding depth to the fragrance.