Tetrahydropyranyl lower alkyl esters and the production of same using a ketene compound

Abstract

The present invention relates to tetrahydropyranyl lower akyl esters and specifically to tetrahydropyranyl acetates, a method for preparation thereof using ketene and use thereof as fragrances and aroma substances.

Claims

1. A compound of the formula (I′) ##STR00070## in which R.sup.1 is hydrogen, R.sup.2 is monosubstituted or polysubstituted phenyl, wherein the substituents are each independently selected from C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.4-alkoxy, R.sup.3 is hydrogen, C.sub.1-C.sub.6-alkyl or C.sub.3-C.sub.6-cycloalkyl, R.sup.4 is hydrogen or methyl, R.sup.6 is C.sub.1-C.sub.3-alkyl, or R.sup.1 and R.sup.2 together with the atoms to which they are bonded form a cyclohexane ring, which is unsubstituted or monosubstituted or polysubstituted with methyl.

2. The compound according to claim 1, wherein the compound is of the formula (I) ##STR00071## in which R.sup.1 is hydrogen, R.sup.2 is monosubstituted or polysubstituted phenyl, wherein the substituents are each independently selected from C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.4-alkoxy, R.sup.3 is hydrogen, C.sub.1-C.sub.6-alkyl or C.sub.3-C.sub.6-cycloalkyl, R.sup.4 is hydrogen or methyl, or R.sup.1 and R.sup.2 together with the atoms to which they are bonded form a cyclohexane ring, which is unsubstituted or monosubstituted or polysubstituted with methyl.

3. The compound according to claim 1, wherein the compound is of the formula (I-A′) ##STR00072## in which R.sup.1 is hydrogen, R.sup.3 is hydrogen or methyl, R.sup.4 is hydrogen or methyl, R.sup.Ph1, R.sup.Ph2, R.sup.Ph3, R.sup.Ph4 and R.sup.Ph5 are each independently hydrogen, C.sub.1-C.sub.6-alkyl or C.sub.1-C.sub.4-alkoxy, R.sup.6 is C.sub.1-C.sub.3-alkyl.

4. The compound according to claim 1, wherein the compound is of the formula (I-A) ##STR00073## in which R.sup.1 is hydrogen, R3 is hydrogen or methyl, R.sup.4 is hydrogen or methyl, R.sup.Ph1, R.sup.Ph2, R.sup.Ph3, R.sup.Ph4 and R.sup.Ph5 are each independently hydrogen, C.sub.1-C.sub.6-alkyl or C.sub.1-C.sub.4-alkoxy.

5. The compound according to claim 3, of the formula (I-A′) or (I-A), ##STR00074## wherein R.sup.1 is hydrogen, R.sup.3 is hydrogen or methyl, R.sup.4 is hydrogen or methyl, 2, 3, 4 or 5 of the residues R.sup.Ph1, R.sup.Ph2, R.sup.Ph3, R.sup.Ph4 and R.sup.Ph5 are hydrogen and the other residues R.sup.Ph1, R.sup.Ph2, R.sup.Ph3, R.sup.Ph4 and R.sup.Ph5 are each independently selected from methyl and methoxy.

6. The compound according to claim 1, wherein the compound is a compound of the formulae (I-A.2), (I-A.3), (I-A.4), (I-A.5), (I-A.6), (I-A.7), (I-A.8), (I-A.9) or (I-A.10) ##STR00075## ##STR00076##

7. The compound according to claim 1, wherein in the compound is of the formula (I-B) ##STR00077## in which R.sup.3 is hydrogen or C.sub.1-C.sub.6-alkyl or C.sub.3-C.sub.6-cycloalkyl, R.sup.4 is hydrogen, R.sup.5 is hydrogen or methyl.

8. The compound according to claim 7, wherein R.sup.3 is C.sub.1-C.sub.4-alkyl or C.sub.3-C.sub.4-cycloalkyl, R.sup.4 is hydrogen, and R.sup.5 is hydrogen or methyl.

9. The compound according to claim 1, wherein the compound is selected from compounds of the formulae (I-B.1), (I-B.2), (I-B.3) and (I-B.4). ##STR00078##

10. A method for preparing the compound of the formula (I) ##STR00079## in which R.sup.1 is hydrogen, R.sup.2 is monosubstituted or polysubstituted phenyl, wherein the substituents are each independently selected from C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.4-alkoxy, R.sup.3 is hydrogen, C.sub.1-C.sub.6-alkyl or C.sub.3-C.sub.6-cycloalkyl, R.sup.4 is hydrogen or methyl, or R.sup.1 and R.sup.2 together with the atoms to which they are bonded form a cyclohexane ring, which is unsubstituted or monosubstituted or polysubstituted with methyl, in which a) providing at least one compound of formula (Ic) ##STR00080## and b) reacting the compound of formula (Ic) with a ketene of the formula (K) ##STR00081## to obtain compounds of the formula (I).

11. An aroma chemical which comprises the compound of the formula (I′) as claimed in claim 1, a compound of the formula (I) or formula (I-A.1) ##STR00082## in which R.sup.1 is hydrogen, R.sup.2 is monosubstituted or polysubstituted phenyl, wherein the substituents are each independently selected from C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.4-alkoxy, R.sup.3 is hydrogen, C.sub.1-C.sub.6-alkyl or C.sub.3-C.sub.6-cycloalkyl, R.sup.4 is hydrogen or methyl, or R.sup.1 and R.sup.2 together with the atoms to which they are bonded form a cyclohexane ring, which is unsubstituted or monosubstituted or polysubstituted with methyl, ##STR00083##

12. The aroma chemical according to claim 11, wherein the compounds of the formula (I′) or (I), or (I-A.1) are used in compositions selected from the group consisting of perfumes, detergents and cleaning compositions, cosmetic agents, body care agents, hygiene articles, products for oral and dental hygiene, scent dispensers, fragrances and pharmaceutical agents.

13. The aroma chemical according to claim 11, wherein i) the compound of the formula (I-A.1) is used for preparing a fragrance having a green and/or dill note, and/or ii) a compound of the formula (I-A.2) ##STR00084## is used for preparing a fragrance having a floral and/or grape hyacinth and/or sweet and/or coumarin note, and/or iii) a compound of the formula (I-A.3) ##STR00085## is used for preparing a fragrance having a phenolic and/or leather and/or technical note, and/or iv) a compound of the formula (I-A.4) ##STR00086## is used for preparing a fragrance having a cresol and/or technical note, and/or v) a compound of the formula (I-A.6) ##STR00087## is used for preparing a fragrance having a floral and/or honey and/or iris note, and/or vi) a compound of the formula (I-A.10) ##STR00088## is used for preparing a fragrance having a natural and/or green and/or herbaceous and/or spearmint and/or cumin and/or fresh note.

14. An aroma substance and/or fragrance composition comprising i) at least one compound of the formula (I′) as claimed in claim 1, a compound of the formula (I) or formula (I-A.1) ##STR00089## in which R.sup.1 is hydrogen, R.sup.2 is monosubstituted or polysubstituted phenyl, wherein the substituents are each independently selected from C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.4-alkoxy, R.sup.3 is hydrogen, C.sub.1-C.sub.6-alkyl or C.sub.3-C.sub.6-cycloalkyl, R.sup.4 is hydrogen or methyl, or R.sup.1 and R.sup.2 together with the atoms to which they are bonded form a cyclohexane ring, which is unsubstituted or monosubstituted or polysubstituted with methyl, ##STR00090## ii) optionally at least one further aroma chemical different from compounds of the formula (I′) or (I) or compound (I-A.1) and iii) optionally at least one diluent, with the proviso that the composition comprises at least one component ii) or iii).

15. A perfumed or fragranced product comprising at least one compound of the formula (I′) as claimed in claim 1, a compound of the formula (I) or formula (I-A.1) ##STR00091## in which R.sup.1 is hydrogen, R.sup.2 is monosubstituted or polysubstituted phenyl, wherein the substituents are each independently selected from C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.4-alkoxy, R.sup.3 is hydrogen, C.sub.1-C.sub.6-alkyl or C.sub.3-C.sub.6-cycloalkyl, R.sup.4 is hydrogen or methyl, or R.sup.1 and R.sup.2 together with the atoms to which they are bonded form a cyclohexane ring, which is unsubstituted or monosubstituted or polysubstituted with methyl, ##STR00092##

16. A method for scenting a product comprising scenting the product with at least one compound of the formula (I′) as claimed in claim 1, a compound of the formula (I) or formula (I-A.1) ##STR00093## in which R.sup.1 is hydrogen, R.sup.2 is monosubstituted or polysubstituted phenyl, wherein the substituents are each independently selected from C.sub.1-C.sub.6-alkyl and C.sub.1-C.sub.4-alkoxy, R.sup.3 is hydrogen, C.sub.1-C.sub.6-alkyl or C.sub.3-C.sub.6-cycloalkyl, R.sup.4 is hydrogen or methyl, or R.sup.1 and R.sup.2 together with the atoms to which they are bonded form a cyclohexane ring, which is unsubstituted or monosubstituted or polysubstituted with methyl, ##STR00094##

17. The method according to claim 16, i) in which one or more compounds of the formula (I-A.1) is used for scenting a product with a green and/or dill note, and/or ii) in which one or more compounds of the formula (I-A.2) ##STR00095## is used for scenting a product with a floral and/or grape hyacinth and/or sweet and/or coumarin note, and/or iii) in which one or more compounds of the formula (I-A.3) ##STR00096## is used for scenting a product with a phenolic and/or leather and/or technical note, and/or iv) in which one or more compounds of the formula (I-A.4) ##STR00097## is used for scenting a product with a cresol and/or technical note, and/or v) in which one or more compounds of the formula (I-A.6) ##STR00098## is used for scenting a product with a floral and/or honey and/or iris note, and/or vi) in which one or more compounds of the formula (I-A.10) ##STR00099## is used for scenting a product with a natural and/or green and/or herbaceous and/or spearmint and/or cumin and/or fresh note.

18. The compound according to claim 1, wherein R.sup.1 and R.sup.2 together with the atoms to which they are bonded form a cyclohexane ring, which is unsubstituted or monosubstituted or polysubstituted with methyl.

Description

EXAMPLES

(1) The following chemicals and abbreviations were used: Amberlyst® 131: acidic ion exchange resin from Rohm and Haas Isoprenol: 3-methyl-3-buten-1-ol Isopulegol: 2-isopropenyl-5-methylcyclohexanol Ketene: ethenone (H.sub.2C═C═O) DMAP: 4-(dimethylamino)pyridine

(2) Gas Chromatographic Analysis Gas chromatographic analyses (GC) were carried out in accordance with the following method: Column: DB WAX 30 m×0.32 mm; FD 0.25 μm Flow rate: 1.5 mL/min N.sub.2 Method A: Start 50° C., then at 3° C./min to 170° C., then at 20° C./min to 230° C. Method B: Start 60° C., then at 2° C./min to 120° C., then at 20° C./min to 230° C. Method C: Start 80° C., then at 2° C./min to 140° C., then at 20° C./min to 230° C.

(3) Aroma Determination

(4) The odor of the respective substances was assessed on a smelling strip. If stated, the intensity is between 1 (very weak) and 6 (very strong).

Example 1

Preparation of Compounds (I-A.1)

(5) ##STR00030##

(6) Benzaldehyde (1961 g, 18.5 mol) and an acidic ion exchange resin (Amberlyst® 131, 375 g) were initially charged at 40° C. Isoprenol (1591 g, 18.5 mol) was added with stirring over 3 h, whereupon the internal temperature increased to ca. 60° C., After addition was complete, the mixture was further stirred at 60° C. for 3 h and then filtered off from the acidic ion exchanger while hot. 2913 g of crude product were obtained with a purity of 67% (yield ca. 55% by gas chromatography, GC method A, R.sub.t=44.4 min).

(7) The product can be purified by means of fractional distillation (top temperature 106 to 130° C. at 3 mbar).

cis-Tetrahydro-4-methyl-2-phenylpyranol, cis-(I-Ac.1)

(8) .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=25.1, 40.1, 48.2, 65.8, 68.9, 77.6, 125.9 (2×), 127.6, 128.4 (2×), 141.9 ppm.

trans-Tetrahydro-4-methyl-2-phenylpyranol, trans-(I-Ac.1)

(9) .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=31.6, 38.2, 46.4, 64.0, 67.9, 75.2, 125.9 (2×), 127.4, 128.3 (2×) 142.6 ppm.

(10) Tetrahydro-4-methyl-2-phenylpyranol (as cis/trans mixture, 10.3 g, 53.5 mmol) was initially charged in 80 ml of toluene at 60° C. Ketene was obtained by pyrolysis of acetone at 700° C. and the pyrolysis gas stream passed through the reaction mixture with vigorous stirring for 8 h. The conversion was >98%. The mixture was allowed to cool and the solvent was removed on the rotary evaporator.

(11) The crude product was purified by means of column chromatography (cyclohexane with 0 to 20% ethyl acetate over 30 min). The product was obtained at a purity of 96% as a mixture of two diastereomers with a cis:trans ratio of 1.4:1.

(12) Odor: green (Int. 4), dill (Int. 4)

cis-Tetrahydro-4-methyl-2-phenylpyranyl acetate, cis-(I-A.1)

(13) R.sub.t=34.8 min (GC method B). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=21.6, 22.4, 37.4, 45.2, 65.0, 76.7, 79.9, 125.8 (2×), 127.6, 128.4 (2×), 141.8, 170.2 ppm.

trans-Tetrahydro-4-methyl-2-phenylpyranyl acetate, trans-(I-A.1)

(14) R.sub.t=34.1 min (GC method B). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=22.4, 26.1, 35.7, 44.2, 63.8, 74.9, 79.2, 125.8 (2×), 127.5, 128.3 (2×), 142.1, 170.4 ppm.

Example 2

Preparation of Compounds (I-A.2)

(15) ##STR00031##

(16) The preparation was effected analogously to example 1, The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 86% as a cis/trans mixture with a cis:trans ratio of 1.7:1.

(17) Odor: floral, grape hyacinth (Int. 3), sweet (Int. 3), coumarin (Int. 2)

(18) Intensity: 2-3

cis-(I-A.2)

(19) R.sub.t=43.4 min (GC method C). MS (EI): m/z (%)=264 [M].sup.+ (15), 204 (35), 189 (100), 173 (10), 137 (39), 135 (35), 69 (11), 43 (13). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.4, 159.0, 134.0, 127.2, 113.7, 80.0, 76.4, 65.0, 55.3, 45.0, 37.4, 22.5, 21.6 ppm.

trans-(I-A.2)

(20) R.sub.t=41.2 min (GC method C). MS (EI): m/z (%)=264 [M].sup.+ (2), 204 (37), 189 (100), 137 (16), 135 (28), 77 (4), 69 (5), 43 (8). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=171.1, 158.9, 134.3, 127.1, 113.7, 79.3, 74.5, 63.9, 55.3, 44.0, 35.7, 26.2, 22.5 ppm.

Example 3

Preparation of Compounds (I-A.3)

(21) ##STR00032##

(22) The preparation was effected analogously to example 1. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 80% as a cis/trans mixture with a cis:trans ratio of 1.2:1.

(23) Odor: phenolic (Int. 3), leather (Int. 2), technical (Int. 3)

(24) Intensity: 3

cis-(I-A.3)

(25) R.sub.t=42.4 min (GC method C). MS (EI): m/z (%)=264 [M].sup.+ (29), 204 (24), 189 (100), 173 (17), 135 (32), 121 (6), 109 (6), 77 (6), 69 (11), 43 (17). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.4, 159.6, 143.8, 129.4, 118.1, 113.2, 111.0, 79.2, 74.8, 63.8, 55.2, 44.2, 35.6, 22.4, 21.6 ppm.

trans-(I-A.3)

(26) R.sub.t=40.5 min (GC method C). MS (EI): m/z (%)=264 [M].sup.+ (2), 204 (38), 189 (100), 173 (7), 135 (21), 43 (8). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.3, 159.6, 143.4, 129.4, 118.1, 113.4, 111.1, 79.9, 76.6, 64.9, 55.2, 45.1, 37.4, 26.1, 22.4 ppm.

Example 4

Preparation of Compounds (I-A.4)

(27) ##STR00033##

(28) The preparation was effected analogously to example 1. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 74% as a cis/trans mixture with a cis:trans ratio of 4:1.

(29) Odor: cresol, technical (Int. 3)

(30) Intensity: 3

cis-(I-A.4)

(31) R.sub.t=39.8 min (GC method C). MS (EI): m/z (%)=264 [M]+ (18), 204 (35), 189 (100), 173 (13), 159 (10), 135 (39), 119 (18), 107 (14), 91 (17), 69 (17), 43 (28). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.3, 155.4, 130.3, 128.3, 126.2, 120.8, 110.1, 80.3, 71.0, 65.2, 55.4, 44.1, 37.7, 22.5, 21.5 ppm.

trans-(I-A.4)

(32) R.sub.t=38.1 min (GC method C). MS (EI): m/z (%)=(264) [M]+ (1), 204 (48), 189 (100), 173 (8), 159 (7), 135 (35), 119 (11), 107 (8), 91 (12), 69 (9), 43 (16). .sup.13C-NMR (125 MHz, CDCl3): δ=170.5, 155.6, 130.7, 128.2, 126.0, 120.7, 110.2, 80.3, 71.0, 64.1, 55.4, 42.6, 36.3, 26.2, 22.5 ppm.

Example 5

Preparation of Compounds (I-A.5)

(33) ##STR00034##

(34) The preparation was effected analogously to example 1. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 96% as a cis/trans mixture with a cis:trans ratio of 5:1.

(35) Odor: not determined.

cis-(I-A.5)

(36) Rt=41.6 min (GC method C). MS (EI): m/z (%)=294 [M].sup.+ (73), 234 (24), 219 (89), 206 (83), 191 (28), 165 (100), 152 (21), 139 (15), 69 (24), 43 (40). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.2, 160.7, 144.2, 103.6, 99.7, 79.8, 76.7, 64.8, 55.3, 45.1, 37.4, 22.4, 21.6 ppm.

trans-(I-A.5)

(37) Rt=41.2 min (GC method C). MS (EI): m/z (%)=294 [M].sup.+ (14), 234 (37), 219 (100), 206 (12), 165 (20), 152 (6), 43 (11). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.4, 160.7, 144.7, 103.6, 99.6, 79.2, 74.9, 63.8, 55.3, 44.3, 35.5, 26.1, 22.4 ppm.

Example 6

Preparation of Compounds (I-A.6)

(38) ##STR00035##

(39) The preparation was effected analogously to example 1. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 97% as a cis/trans mixture with a cis:trans ratio of 45:1.

(40) Odor: floral (Int. 2), honey (Int. 2), iris (Int. 2)

(41) Intensity: 1-2

cis-(I-A.6)

(42) R.sub.t=37.9 min (GC method C). MS (EI): m/z (%)=248 [M].sup.+ (2), 188 (40), 173 (100), 159 (3), 145 (5), 119 (22), 91 (11), 69 (10), 43 (14). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.2, 138.8, 137.2, 129.0, 125.8, 80.0, 76.6, 65.0, 45.1, 37.4, 22.4, 21.5, 21.1 ppm.

trans-(I-A.6)

(43) R.sub.t=36.8 min (GC method C). MS (EI): m/z (%)=188 (40), 173 (100), 159 (2), 145 (4), 119 (21), 91 (9), 69 (6), 43 (9).

Example 7

Preparation of Compounds (I-A.7)

(44) ##STR00036##

(45) The preparation was effected analogously to example 1. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 84% as a cis/trans mixture with a cis:trans ratio of 2.8:1.

(46) Odor: lily of the valley (Int. 1), cresol/smoke (Int. 2), technical (Int. 2)

cis-(I-A.7)

(47) R.sub.t=37.7 min (GC method C). MS (EI): m/z (%)=248 [M].sup.+ (2), 188 (46), 173 (100), 145 (7), 119 (27), 91 (16), 69 (16), 43 (25). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.3, 141.6, 138.0, 128.4, 128.3, 126.5, 122.9, 79.9, 76.8, 65.0, 45.1, 37.4, 22.5, 21.5, 21.4 ppm.

trans-(I-A.7)

(48) R.sub.t=36.7 min (GC method C). MS (EI): m/z (%)=248 [M].sup.+ (<1), 188 (41), 173 (100), 145 (6), 119 (23), 91 (12), 69 (8), 43 (15). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.4, 142.0, 138.0, 129.4, 128.24, 128.22, 126.4, 79.2, 74.9, 63.9, 44.2, 35.7, 26.1, 22.4, 21.5 ppm.

Example 8

Preparation of Compounds (I-A.8)

(49) ##STR00037##

(50) The preparation was effected analogously to example 1. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 86% as a cis/trans mixture with a cis:trans ratio of 3.8:1.

(51) Odor: solvent (Int. 3), rubber (Int. 4), hot angle grinder

cis-(I-A.8)

(52) R.sub.t=37.7 min (GC method C). MS (EI): m/z (%)=248 [M].sup.+ (4), 188 (54), 173 (100), 143 (14), 119 (34), 91 (21), 69 (26), 43 (31). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.2, 139.8, 134.0, 130.2, 127.3, 126.3, 125.2, 80.0, 73.6, 65.2, 44.0, 37.5, 22.5, 21.4, 18.9 ppm.

trans-(I-A.8)

(53) R.sub.t=36.5 min (GC method C). MS (EI): m/z (%)=248 [M].sup.+ (<1), 188 (50), 173 (100), 145 (10), 119 (25), 91 (15), 69 (14), 43 (18). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.4, 140.2, 134.1, 130.2, 127.1, 126.2, 125.0, 79.4, 73.8, 64.0, 42.8, 36.1, 26.1, 22.4, 18.8 ppm.

Example 9

Preparation of Compounds (I-A.9)

(54) ##STR00038##

(55) The preparation was effected analogously to example 1. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 70% as a cis/trans mixture with a cis:trans ratio of 3:1.

(56) Odor: not determined

cis-(I-A.9)

(57) R.sub.t=38.8 min (GC method C). MS (EI): m/z (%)=262 [M].sup.+ (4), 202 (41), 187 (100), 159 (8), 133 (32), 119 (6), 105 (9), 91 (9), 69 (11), 43 (18). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.2, 141.6, 137.9, 129.2, 123.6, 80.0, 76.9, 65.0, 45.0, 37.4, 22.4, 21.5, 21.3 ppm.

trans-(I-A.9)

(58) R.sub.t=37.7 min (GC method C). MS (EI): m/z (%)=262 [M].sup.+ (1), 202 (39), 187 (100), 159 (6), 133 (25), 119 (4), 105 (7), 91 (6), 69 (6), 43 (11). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.4, 142.0, 137.8, 129.2, 123.5, 79.3, 75.0, 65.0, 45.0, 37.4, 26.1, 22.3, 21.3 ppm.

Example 10

Preparation of Compounds (I-B.3)

(59) ##STR00039##

(60) n-Butanal (120 g, 1.66 mol) was initially charged with an acidic ion exchange resin (Amberlyst® 131, 50 g) at room temperature and isopulegol (240 g, 1.56 mol) was added over 20 minutes. The temperature increased to ca. 65° C. during the addition. After the addition was complete, the mixture was stirred at 70° C. for 8 h, allowed to cool and the mixture diluted with water and filtered off from the acidic ion exchanger. The phases were separated, the organic phase diluted with toluene and washed with saturated aqueous NaHCO.sub.3 solution and NaCl solution. Subsequently, the solvent was removed on the rotary evaporator.

(61) The product was obtained after fractional distillation as a viscous liquid (110.4 g, 30%) as a diastereomeric mixture of the alcohols with an (alpha)-(I-Bc.3):(beta)-(I-Bc.3) ratio of 1:4.

(62) (Alpha)-(I-Bc.3)

(63) ##STR00040##

(64) R.sub.t=32.6 (GC method B). MS (EI): m/z (%)=225 [M-H].sup.+ (<1), 208 (56), 193 (52), 183 (27), 165 (43), 139 (100), 121 (19), 111 (13), 95 (24), 81 (53), 71 (29), 55 (23), 43 (50). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=75.0, 72.1, 69.0, 50.3, 47.0, 42.0, 38.8, 35.0, 31.5, 28.4, 22.9, 22.5, 19.2, 14.5 ppm.

(65) (Beta)-(I-Bc.3)

(66) ##STR00041##

(67) R.sub.t=33.3 (GC method B). MS (EI): m/z (%)=225 [M-H].sup.+ (<1), 208 (4), 183 (45), 165 (8), 139 (100), 131 (24), 121 (13), 113 (27), 95 (25), 81 (53), 71 (24), 55 (19), 43 (51). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=76.8, 74.4, 70.8, 52.3, 48.4, 41.6, 38.4, 34.4, 31.4, 23.0, 22.2, 21.4, 18.7, 14.1 ppm.

(68) The alcohol (as a diastereomeric mixture, 10.2 g, 42 mmol) was initially charged in toluene at 60° C. Ketene was obtained by pyrolysis of acetone at 700° C. and the pyrolysis gas stream passed through the reaction mixture with vigorous stirring for 8.5 h. The conversion was >90%. The mixture was allowed to cool and the solvent was removed on the rotary evaporator.

(69) The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 96% as a mixture of two diastereomers with an (alpha)-(I-B.3):(beta)-(I-B.3) ratio of 1:10.

(70) Odor: not determined

(71) (Alpha)-(I-B.3)

(72) ##STR00042##

(73) R.sub.t=31.5 min (GC method B). MS (EI): m/z (%)=267 [M-H].sup.+ (<1), 208 (39), 193 (64), 180 (15), 165 (100), 139 (8), 121 (18), 107 (15), 93 (23), 81 (46), 67 (9), 55 (17), 43 (32). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.4, 80.5, 74.6, 72.2, 51.4, 41.4, 40.3, 37.9, 34.4, 31.1, 23.4, 22.5, 22.2, 22.1, 18.7, 14.0 ppm.

(74) (Beta)-(I-B.3)

(75) ##STR00043##

(76) R.sub.t=32.8 min (GC method B). MS (EI): m/z (%)=208 (27), 193 (22), 179 (9), 165 (100), 147 (7) 136 (12), 121 (25), 107 (13), 93 (20), 81 (40), 67 (7), 55 (12), 43 (24). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.1, 82.5, 75.9, 73.6, 50.0, 43.9, 41.6, 38.4, 34.2, 31.3, 23.3, 22.5, 22.2, 18.8, 18.4, 14.1 ppm.

Example 11

Preparation of Compounds (I-B.1)

(77) ##STR00044##

(78) The preparation was effected analogously to example 10. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 84% as a mixture of two isomers with an (alpha)-(I-B.1):(beta)-(I-B.1) ratio of 1:16.

(79) Odor: not determined

(80) (Alpha)-(I-B.1)

(81) ##STR00045##

(82) R.sub.t=30.2 min (GC method C). MS (EI): m/z (%)=180 (45), 165 (100), 151 (22), 137 (24), 122 (15), 107 (14), 95 (16), 81 (37), 67 (9), 55 (11), 43 (33).

(83) (Beta)-(I-B.1)

(84) ##STR00046##

(85) R.sub.t=32.3 min (GC method C). MS (EI): m/z (%)=239 [M-H]+ (<1), 180 (65), 165 (100), 151 (31), 137 (36), 121 (44), 107 (17), 95 (23), 81 (58), 67 (12), 55 (14), 43 (49). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.5, 82.3, 75.8, 69.9, 49.6, 45.5, 41.6, 34.2, 31.3, 23.2, 22.5, 22.2, 21.9, 18.3 ppm.

Example 12

Preparation of Compounds (I-B.2)

(86) ##STR00047##

(87) The preparation was effected analogously to example 10. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 91% as a mixture of two isomers with an (alpha)-(I-B.2):(beta)-(I-B.2) ratio of 1:6.5.

(88) Odor: not determined

(89) (Alpha)-(I-B.2)

(90) ##STR00048##

(91) R.sub.t=31.5 min (GC method C). MS (EI): m/z (%)=194 (47), 179 (81), 165 (100), 151 (18), 139 (6), 121 (10), 107 (9), 95 (12), 81 (25), 67 (5), 55 (9), 43 (20). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.4, 80.5, 74.6, 73.7, 51.5, 41.4, 40.0, 34.4, 31.2, 28.7, 23.4, 22.6, 22.3, 22.2, 9.9 ppm.

(92) (Beta)-(I-B.2)

(93) ##STR00049##

(94) R.sub.t=33.0 min (GC method C). MS (EI): m/z (%)=194 (32), 179 (29), 165 (100), 151 (11), 137 (10), 121 (22), 107 (8), 95 (11), 81 (25), 67 (5), 55 (7), 43 (19). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.5, 82.5, 75.8, 75.2, 50.0, 43.4, 41.6, 34.2, 31.3, 29.1, 23.3, 22.5, 22.2, 18.4, 10.0 ppm.

Example 13

Preparation of Compounds (I-B.4)

(95) ##STR00050##

(96) The preparation was effected analogously to example 10, The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 70% as one isomer. A low-boiling by-product could be removed under reduced pressure and the purity could be increased to >90%.

(97) Odor: not determined

(98) (Beta)-(I-B.4)

(99) ##STR00051##

(100) R.sub.t=35.1 min (GC method C). MS (EI): m/z (%)=266 [M].sup.+ (1), 206 (68), 191 (100), 178 (49), 165 (23), 149 (9), 136 (47), 121 (52), 107 (30), 95 (41), 81 (58), 69 (18), 55 (16), 43 (53). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=170.5, 82.2, 78.7, 75.8, 49.9, 43.7, 41.6, 34.2, 31.3, 23.3, 22.5, 22.2, 18.2, 16.2, 3.5, 2.0 ppm.

Example 14

Preparation of Compound (I-A.10)

(101) ##STR00052##

(102) 4-Methyl-2-(p-tolyl)tetrahydropyran-4-ol (4.13 g; 20 mmol; 1.0 eq.), Et.sub.3N (2.23 g; 22 mmol; 1.1 eq.) and DMAP (240 mg; 2 mmol; 0.1 eq.) were initially charged in toluene (40 mL) at RT. The mixture was heated to 60° C. and butyryl chloride (2.24 g; 21 mmol, 1.05 eq.) was added dropwise with stirring. After addition was complete, the mixture was stirred for 6 h. The mixture was then allowed to cool to RT, water (10 g) was added to the mixture and the phases were separated. The solvent was removed from the organic phase on a rotary evaporator and the product was purified by column chromatography (cyclohexane/ethyl acetate) to a purity of >90%.

(103) Odor: natural (5), green (5), herbaceous (5), spearmint (4), cumin (4), fresh (4). Intensity 3.

cis-Isomer

(104) ##STR00053##

(105) R.sub.t=39.7 min (GC method C). MS (EI): m/z (%)=276 (1) [M].sup.+, 188 (36), 173 (100), 145 (6), 121 (17), 119 (18), 105 (4), 91 (10), 71 (12), 69 (15), 43 (16). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=172.8, 138.9, 137.2, 129.0, 125.8, 79.7, 76.6, 65.0, 45.3, 37.5, 37.4, 21.6, 21.1, 18.5, 13.6 ppm.

COMPARATIVE EXAMPLES

General Preparation Method of Tetrahydropyranol Derivatives from Benzaldehydes

(106) To prepare the various tetrahydropyranol derivatives the respective benzaldehyde was initially charged at room temperature with Amberlyst 131 wet® (10% by weight based on the sum total of the masses of benzaldehyde and isoprenol) and an equimolar amount of isoprenol was rapidly added. If required, particularly if the benzaldehyde concerned was solid at room temperature, toluene was used as solvent. The reaction mixture was then stirred at 60° C. for 5 h, subsequently cooled, the acidic ion exchanger was filtered off and washed with toluene. Any solvents were removed on the rotary evaporator. Fragrance samples were obtained either by purification by means of distillation, column chromatography or by recrystallization.

Comparative Example 1

Preparation of Compounds (I-Ac.2)

(107) ##STR00054##

(108) The preparation was effected analogously to the general preparation method of tetrahydropyranol derivatives from benzaldehydes. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 99% as a cis/trans mixture with a cis:trans ratio of 2:1.

(109) The alcohol was odorless.

cis-Isomer

(110) R.sub.t=44.8 min (GC method C). MS (EI): m/z (%)=222 [M].sup.+ (24), 204 (32), 189 (100), 135 (55), 43 (13). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=159.0, 134.2, 127.3, 113.7, 77.2, 69.0, 65.8, 55.2, 48.0, 40.2, 25.2 ppm.

trans-Isomer

(111) R.sub.t=43.7 min (GC method C). MS (EI): m/z (%)=222 [M].sup.+ (22), 204 (31), 189 (100), 135 (49), 43 (11). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=158.8, 134.8, 127.3, 113.7, 74.8, 68.0, 64.1, 55.2, 46.3, 38.3, 31.7 ppm.

Comparative Example 2

Preparation of Compounds (I-Ac.3)

(112) ##STR00055##

(113) The preparation was effected analogously to the general preparation method of tetrahydropyranol derivatives from benzaldehydes. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 99% as a cis/trans mixture with a cis:trans ratio of 1.1:1.

(114) Odor: technical.

cis-Isomer

(115) R.sub.t=44.1 min (GC method C). MS (EI): m/z (%)=222 [M].sup.+ (22), 204 (37), 189 (100), 177 (9), 135 (48), 109 (12), 77 (10), 43 (17). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=159.6, 143.6, 129.4, 118.2, 113.3, 111.2, 77.5, 69.1, 65.8, 55.2, 48.3, 40.2, 25.3 ppm.

trans-Isomer

(116) R.sub.t=43.2 min (GC method C). MS (EI): m/z (%)=222 [M].sup.+ (26), 204 (35), 189 (100), 135 (55), 119 (13), 108 (11), 77 (10), 43 (20). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=159.6, 144.3, 129.3, 118.1, 113.1, 111.1, 75.1, 68.1, 64.0, 55.2, 46.6, 38.4, 31.7 ppm.

Comparative Example 3

Preparation of Compounds (I-Ac.4)

(117) ##STR00056##

(118) The preparation was effected analogously to the general preparation method of tetrahydropyranol derivatives from benzaldehydes. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 96% as a cis/trans mixture with a cis:trans ratio of 1.4:1.

(119) Odor: technical.

cis-Isomer

(120) R.sub.t=40.7 min (GC method C). MS (EI): m/z (%)=222 [M].sup.+ (23), 204 (31), 189 (100), 177 (6), 135 (54), 119 (22), 107 (17), 91 (19), 77 (11), 43 (18). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=155.4, 130.5, 128.2, 126.1, 120.7, 110.1, 71.7, 69.2, 66.0, 55.3, 47.1, 40.5, 25.1 ppm.

trans-Isomer

(121) R.sub.t=39.7 min (GC method C); MS (EI): m/z (%)=222 [M].sup.+ (18), 204 (35), 189 (100), 135 (46), 121 (10), 119 (18), 107 (14), 91 (15), 43 (13); .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=155.5, 131.1, 128.0, 126.2, 120.7, 110.1, 69.4, 68.2, 64.2, 55.3, 45.4, 38.4, 31.6 ppm.

Comparative Example 4

Preparation of Compounds (I-Ac.5)

(122) ##STR00057##

(123) The preparation was effected analogously to the general preparation method of tetrahydropyranol derivatives from benzaldehydes. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 98% as a cis/trans mixture with a cis:trans ratio of 2.1:1.

(124) The product was odorless.

cis-Isomer

(125) R.sub.t=60.1 min (GC method C). MS (EI): m/z (%)=252 [M].sup.+ (27), 219 (15), 206 (8), 191 (4), 165 (100), 152 (14), 139 (10). .sup.13C-NMR (125 MHz, acetone-D.sub.6): δ=161.6, 146.8, 104.3, 99.6, 78.0, 68.4, 66.2, 55.5, 50.0, 41.3, 25.6 ppm.

trans-Isomer

(126) R.sub.t=58.3 min (GC method C). MS (EI): m/z (%)=252 [M].sup.+ (66), 219 (69), 206 (10), 191 (7), 165 (100), 152 (13), 139 (15), 43 (11). .sup.13C-NMR (125 MHz, acetone-D.sub.6): δ=161.6, 146.8, 104.3, 99.4, 75.7, 67.5, 64.5, 55.5, 48.0, 39.2, 31.9 ppm.

Comparative Example 5

Preparation of Compounds (I-Ac.6)

(127) ##STR00058##

(128) The preparation was effected analogously to the general preparation method of tetrahydropyranol derivatives from benzaldehydes. The crude product was recrystallized from n-heptane. The cis isomer was obtained at a purity of 99%.

(129) The product was odorless.

cis-Isomer

(130) R.sub.t=38.6 min (GC method C). MS (EI): m/z (%)=206 [M].sup.+ (5), 188 (52), 173 (100), 119 (36), 103(4), 91 (18), 71 (9), 43 (14). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=139.0, 137.2, 129.0, 125.9, 77.5, 69.0, 65.8, 48.2, 40.2, 25.2, 21.1 ppm.

trans-Isomer

(131) R.sub.t=38.1 min (GC method C).

Comparative Example 6

Preparation of Compounds (I-Ac.7)

(132) ##STR00059##

(133) The preparation was effected analogously to the general preparation method of tetrahydropyranol derivatives from benzaldehydes. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 97% as a cis/trans mixture with a cis:trans ratio of 9:1.

(134) The product was odorless.

cis-Isomer

(135) R.sub.t=38.5 min (GC method C). MS (EI): m/z (%)=206 [M].sup.+ (4), 188 (58), 173 (100), 119 (35), 91 (19), 71 (10), 43 (16). .sup.13C-NMR (125 MHz, acetone-D.sub.6): δ=144.2, 138.2, 128.8, 128.4, 127.1, 123.6, 78.0, 68.4, 66.2, 50.0, 41.3, 25.5, 21.4 ppm.

trans-Isomer

(136) R.sub.t=38.0 min (GC method C). MS (EI): m/z (%)=206 [M].sup.+ (2), 188 (60), 173 (100), 119 (31), 91 (15), 71 (8), 58 (6), 43 (12).

Comparative Example 7

Preparation of Compounds (I-Ac.8)

(137) ##STR00060##

(138) The preparation was effected analogously to the general preparation method of tetrahydropyranol derivatives from benzaldehydes. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 98%.

(139) Odor: balsamic (2), cresol (2).

cis-Isomer

(140) R.sub.t=38.6 min (GC method C). MS (EI): m/z (%)=206 [M].sup.+ (4), 188 (53), 173 (100), 118 (64), 91 (37), 71 (24), 58 (16), 43 (37). .sup.13C-NMR (125 MHz, acetone-D.sub.6): δ=142.1, 134.7, 130.8, 127.6, 126.7, 126.1, 75.1, 68.5, 66.4, 48.4, 41.4, 25.4, 18.9 ppm.

trans-Isomer

(141) R.sub.t=37.8 min (GC method C). MS (EI): m/z (%)=206 [M].sup.+ (8), 188 (49), 173 (100), 118 (49), 91 (32), 71 (18), 58 (14), 43 (29). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=140.6, 134.5, 130.1, 127.1, 126.1, 125.3, 71.9, 68.2, 64.2, 45.1, 38.5, 31.7, 19.0 ppm.

Comparative Example 8

Preparation of Compounds (I-Ac.9)

(142) ##STR00061##

(143) The preparation was effected analogously to the general preparation method of tetrahydropyranol derivatives from benzaldehydes. The product was obtained after column chromatography (cyclohexane/ethyl acetate) as the cis isomer at a purity of 95%.

(144) The product was odorless.

(145) cis-Isomer: R.sub.t=39.7 min (GC method C); MS (EI): m/z (%)=220 [M].sup.+ (13), 202 (53), 187 (100), 159 (6), 133 (45), 117 (15), 107 (17), 91 (14), 71 (12), 43 (15); .sup.13C-NMR (125 MHz, acetone-D.sub.6): δ=144.2, 138.1, 129.3, 124.3, 78.1, 68.4, 66.2, 50.1, 41.4, 25.6, 21.4 ppm.

(146) trans-Isomer: R.sub.t=39.2 min (GC method C); MS (EI): m/z (%)=220 [M].sup.+ (10), 202 (51), 187 (100), 159 (6), 133 (41), 117 (12), 107 (14), 91 (14), 71 (11), 58 (5), 43 (15); .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=142.5, 137.9, 129.0, 123.6, 75.3, 68.2, 64.1, 46.5, 38.4, 31.8, 21.3 ppm.

COMPARATIVE EXAMPLES

General Preparation Method of Tetrahydropyranol Derivatives from Aliphatic Aldehydes

(147) To prepare the various tetrahydropyranol derivatives the respective aldehyde was initially charged at room temperature with Amberlyst 131 wet® (10% by weight based on the sum total of the masses of the relevant aldehyde and isopulegol) with toluene as solvent if required and an equimolar amount of isopulegol was rapidly added. The reaction mixture was then stirred at 60° C. for 5 h, subsequently cooled, the acidic ion exchanger was filtered off and washed with toluene. Any solvents were removed on the rotary evaporator. Fragrance samples were obtained either by purification by means of distillation, column chromatography or by recrystallization.

Comparative Example 9

Preparation of Compounds (I-Bc.1)

(148) ##STR00062##

(149) The preparation was effected analogously to the general preparation method of tetrahydropyranol derivatives from aliphatic aldehydes. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 97% as an isomeric mixture with an (alpha)-(I-Bc.1):(beta)-(I-Bc.1) ratio of 1:5.5.

(150) Odor: no specific odor.

(151) (Alpha)-(I-Bc.1)

(152) ##STR00063##

(153) R.sub.t=32.2 min (GC method C). MS (EI): m/z (%)=198 [M].sup.+ (1), 180 (71), 165-(100), 151 (32), 137 (31), 121 (10), 95 (24), 81 (65), 71 (30), 55 (18), 43 (52). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=75.0, 69.3, 68.5, 49.4, 47.9, 41.4, 34.4, 31.3, 28.2, 22.5, 22.3, 21.7 ppm.

(154) ##STR00064##

(155) R.sub.t=33.1 min (GC method C). MS (EI): m/z (%)=198 [M].sup.+ (<1), 183 (10), 165 (7), 139 (15), 103 (100), 95 (26), 81 (77), 71 (34), 55 (19), 43 (59). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=76.9, 70.7, 70.5, 51.9, 50.2, 41.6, 34.4, 31.5, 23.0, 22.3, 22.0, 21.4 ppm.

Comparative Example 10

Preparation of Compounds (I-Bc.2)

(156) ##STR00065##

(157) The preparation was effected analogously to the general preparation method of tetrahydropyranol derivatives from aliphatic aldehydes. The product was obtained after column chromatography (cyclohexane/ethyl acetate) at a purity of 92% as an isomeric mixture with an (alpha)-(I-Bc.1):(beta)-(I-Bc.1) ratio of 1:5.6.

(158) Odor: no specific odor.

(159) (Alpha)-(I-Bc.2)

(160) ##STR00066##

(161) R.sub.t=33.0 min (GC method C). MS (EI): m/z (%)=212 [M].sup.+ (1), 194 (83), 179 (81), 165 (59), 151 (26), 139 (100), 121 (19), 111 (14), 95 (26), 71 (23), 55 (18), 81 (56), 43 (42). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=75.0, 73.8, 69.3, 49.7, 45.7, 41.4, 34.4, 31.3, 28.9, 28.3, 22.6, 22.2, 10.0 ppm.

(162) (Beta)-(I-Bc.2)

(163) ##STR00067##

(164) R.sub.t=33.8 min (GC method C). MS (EI): m/z (%)=197 (6), 183 (53), 165 (6), 139 (100), 117 (34), 99 (29), 81 (50), 43 (41). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=76.9, 75.9, 70.8, 52.3, 48.0, 41.6, 34.4, 31.5, 29.1, 23.1, 22.3, 21.5, 10.0 ppm.

Comparative Example 11

Preparation of Compounds (I-Bc.4)

(165) ##STR00068##

(166) The preparation was effected analogously to the general preparation method of tetrahydropyranol derivatives from aliphatic aldehydes. The product was recrystallized from n-heptane and obtained as a pure isomer.

(167) Odor: no specific odor.

(168) (Beta)-(I-Bc.4)

(169) ##STR00069##

(170) R.sub.t=35.6 min (GC method C). MS (EI): m/z (%)=224 [M].sup.+ (2), 109 (39), 191 (58),165 (82), 139 (84), 111 (91), 95(47), 81 (85), 71 (100), 43 (99). .sup.13C-NMR (125 MHz, CDCl.sub.3): δ=77.1, 70.8, 59.6, 52.3, 48.2, 41.8, 34.5, 31.6, 23.2, 22.4, 21.4, 16.3, 3.7, 2.0 ppm.