Process

Abstract

The regio-selective functionalization of a dialkyl benzene compound

##STR00001##

wherein the ratio of the compound functionalized at position (a) to the compound functionalized at the position (b) is at least 70:30, more particularly at least 80:20, still more particularly at least 85:15, and still more particularly at least 90:10, characterised in that the substituent R is an isobutyl group.

Claims

1. (canceled)

2. (canceled)

3. (canceled)

4. (canceled)

5. (canceled)

6. (canceled)

7. (canceled)

8. A compound according to the formula I ##STR00015## wherein R.sub.1 through R.sub.4 is independently H or methyl; and R.sub.5 is a branched or linear, saturated or unsaturated C.sub.3-C.sub.7 alkyl, alkenyl, cycloalkyl or cycloalkenyl residue; wherein the compound is a perfume ingredient.

9. The compound according to claim 8, wherein the compound exhibits muguet odour characteristics.

10. A compound according to formula I ##STR00016## wherein R.sub.1 through R.sub.4 is independently H or methyl; and R.sub.5 is a branched or linear, saturated or unsaturated C.sub.3-C.sub.7 alkyl or alkenyl, cycloalkyl or cycloalkenyl residue; and wherein said compound is not 4-(4-(tert-butyl)phenyl)butanal, 4-(4-isopropylphenyl)butanal, 4-(4-isobutylphenyl)butanal, 4-(4-(tert-butyl)phenyl)-3-methylbutanal.

11. A pro-perfume, adapted to release the compound represented by the formula I ##STR00017## wherein R.sub.1 through R.sub.4 is independently H or methyl; and R.sub.5 is a branched or linear, saturated or unsaturated C.sub.3-C.sub.7 alkyl, alkenyl, cycloalkyl or cycloalkenyl residue.

12. A perfume composition comprising a compound represented by the formula I ##STR00018## wherein R.sub.1 through R.sub.4 is independently H or methyl; and R.sub.5 is a branched or linear, saturated or unsaturated C.sub.3-C.sub.7 alkyl, alkenyl, cycloalkyl or cycloalkenyl residue; and/or, comprising a pro-perfume adapted to release the compound represented by the formula I.

13. A perfume composition according to claim 12 that is free of any aryl-substituted propanal, odourants that are unsubstituted on the aryl ring at a position ortho to the substituent bearing the aldehyde functionality and/or not bearing butanal as the aldehyde functionality, in particular Lilial.

14. A perfume composition according to claim 12 comprising one or more additional fragrance ingredients.

15. A personal care or household care composition comprising a compound according to the formula I ##STR00019## wherein R.sub.1 through R.sub.4 is independently H or methyl; and R.sub.5 is a branched or linear, saturated or unsaturated C.sub.3-C.sub.7 alkyl, alkenyl, cycloalkyl or cycloalkenyl residue.

16. A personal care or household care composition according to claim 15, further comprising one or more enzymes.

17. A personal or household care composition according to claim 15 which is a textile treatment product.

18. A personal or household care composition according to claim 15 which is a detergent composition.

19. A method of imparting muguet odour characteristics to a fine fragrance or consumer product comprising the step of: adding thereto an aryl-substituted butanal compound according to the formula I ##STR00020## wherein R.sub.1 through R.sub.4 is independently H or methyl; and R.sub.5 is a branched or linear, saturated or unsaturated C.sub.3-C.sub.7 alkyl, alkenyl, cycloalkyl or cycloalkenyl residue; and/or a pro-perfume adapted to release the compound represented by the formula I, with the proviso that said fine fragrance or consumer product excludes any aryl-substituted butanal compounds, which have a greatly reduced susceptibility of said compounds to undergo an enzymatically-mediated degradation to their benzoic acid derivatives when incubated with hepatocytes isolated from rats, said compounds being suitable for addition on the basis that they do far less degrade to their benzoic acid derivatives in comparison to Lilial.

20. The pro-perfume of claim 11, which is an aminal and/or enamine of the compound represented by the formula I.

21. A perfume composition according to claim 147, wherein the additional fragrance ingredients are selected from: 3-(4-isobutyl-2-methylphenyl)propanal; and, 3-(4-(tert-butyl)-2-methylphenyl)-2-methylpropanal.

22. A personal care or household care composition comprising a perfume composition according to claim 12.

23. A personal care or household care composition comprising a perfume composition according to claim 13.

24. A personal care or household care composition comprising a perfume composition according to claim 14.

Description

EXAMPLE 1: SYNTHESIS OF 3-(4-ISOBUTYL-2-METHYLPHENYL)PROPANAL

A) 3-isobutyl toluene (II)

[0050] A mixture of freshly distilled 3- and 5-isobutyl-1-methylcyclohex-1-ene (700 g, 4.6 mol) was passed vertically through a glass tube (250 cm) filled with 100 g of palladium on alumina pellets (Aldrich, art. 205745) and heated to 200 C. The cyclohexene was passed though the column at a rate of 2 ml/min at 32 mbar. The crude (II) was condensed and collected in a recipient at the bottom of the column. The product, containing 90% (II) and 10% 1-isobutyl-3-methylcyclohexane was purified by distillation (bp. 105 C., 88 mbar) over a 50 cm packed column to afford pure (II) (566 g, 83% yield).

[0051] .sup.1H-NMR (400 MHz, CDCl3): =7.24 (dd, J=7.58 Hz, 1H), 7.05 (m, 3H), 2.52 (d, J=7.07 Hz, 2H), 2.41 (s, 3H), 1.94 (m, 1H), 0.99 (d, J=6.82 Hz, 6H) ppm. .sup.13C-NMR (400 MHz, CDCl3): =141.7 (s), 137.6 (s), 130.0 (d), 128.0 (d), 126.4 (d), 126.2 (d), 45.5 (t), 30.3 (d), 22.5 (2q), 21.5 (q) ppm. GC/MS (EI): 148 (M.sup.+, 26), 106 (42), 105 (100), 103 (8), 91 (18), 79 (7), 77 (11), 43 (8), 41 (8), 39 (8).

B) 2-methyl-4-isobutyl bromide (IV)

[0052] The reactor was flushed with nitrogen and (II) (5440 g, 36.7 mol) was added. Iron powder (102 g, 1.8 mol) and iodine (1 g) was added while stirring. The mixture was cooled to 10 C. and dibromine (5860 g, 36.7 mol) was added drop wise over 6 hours at 10 C. During the addition one molar equivalent of hydro bromic acid is produced that must be absorbed by appropriate means. Following the addition the reaction was stirred for 1 h at room temperature and then washed with 101 of NaOH 2M. The mixture was extracted twice with hexane, then the organic layers were combined, washed with water and brine and concentrated in vacuo. Short path distillation (120 C., 8 mbar) afforded (IV) (4580 g, 55% yield).

[0053] .sup.1H-NMR (400 MHz, CDCl3): =7.46 (d, J=8.07 Hz, 1H), 7.06 (s, 1H), 6.87 (d, J=8.07 Hz, 1H), 2.45 (d, J=7.09 Hz, 2H), 2.42 (s, 3H), 1.88 (m, 1H), 0.95 (d, J=6.60 Hz, 6H) ppm. .sup.13C-NMR (400 MHz, CDCl3): =141.0 (s), 137.2 (s), 132.0 (d), 131.7 (d), 128.3 (d), 122.0 (s), 44.7 (t), 30.1 (d), 22.9 (q), 22.3 (2q) ppm. GC/MS (EI): 228 (M.sup.+, 20), 226 (M.sup.+, 20), 186 (21), 185 (97), 184 (23), 183 (100), 105 (19), 104 (14), 103 (17), 77 (13).

C) 2-methyl-4-isobutyl benzaldehyde (III)

[0054] Magnesium turnings (171 g, 7 mol) was placed in a reactor and covered with THF. A small amount (6 ml) of (IV) was added and the reaction initiated by gentle heating. The remaining (IV) (1589 g, 7 mol) was mixed with THF (3 l) and added drop wise while maintaining a gentle reflux (70-85 C.) without external heating. After the addition was complete, the mixture was stirred at reflux for an additional hour. The reaction mixture was cooled to 10 C. and dimethyl formamide (566 g, 7.7 mol) was added drop wise over 1 hour keeping the temperature below 30 C. The reaction mixture was stirred for 1 hour and then quenched with ice cold HCl (2M). The mixture was extracted with hexane, the organic layers were combined and washed with water and brine. The solution was dried over MgSO.sub.4 and concentrated in vacuo. Distillation over a 100 cm packed column (b.p. 105 C., 2.5 mbar) gave pure (III) (592 g, 48% yield).

[0055] .sup.1H-NMR (400 MHz, CDCl3): =10.22 (s, 1H), 7.71 (d, J=7.82 Hz, 1H), 7.14 (d, J=7.58 Hz, 1H), 7.04 (s, 1H), 2.65 (s, 3H), 2.50 (d, J=7.34 Hz, 2H), 1.91 (m, 1H), 0.92 (d, J=6.85 Hz, 6H) ppm. .sup.13C-NMR (400 MHz, CDCl3): =192.3 (d), 148.2 (s), 140.5 (s), 132.6 (d), 132.3 (d), 132.2 (s), 127.1 (d), 45.4 (t), 30.1 (d), 22.4 (2q), 19.6 (q) ppm. GC/MS (EI): 176 (M.sup.+, 53), 134 (100), 133 (38), 106 (14), 105 (70), 103 (14), 91 (37), 77 (19), 43 (30), 41 (14).

D) 3-(4-isobutyl-2-methyl phenyl)propen-2-al (VI)

[0056] A reactor was charged with (III) (1 kg, 5.68 mol), methanol (400 ml) and trimethyl orthoformate (900 g, 8.49 mol). The reaction mixture was cooled to 10 C. and hydrochloric acid (37%, 1 g) was added. The reaction was exothermal and the temperature was allowed to rise to 25 C., the mixture was stirred for 30 minutes. The reaction was quenched with sodium acetate (20 g) and the volatiles were removed by distillation under vacuum. The residual acetal was charged into a second reactor and boron trifluoride etherate (1 g) was added and ethyl vinyl ether (538 g, 7.5 mol) was added drop wise over 4 hours while maintaining the temperature at 25-30 C. The reaction mass was quenched with saturated sodium carbonate (500 ml). The resulting crude methoxy ethoxy acetals were hydrolysed with water (500 ml) containing hydrochloric acid (37%, 50 g) at 90 C. for 5 hours. The intermediate (VI) was short path distilled at 120 C.

[0057] .sup.1H-NMR (400 MHz, CDCl3): =9.87 (s, 1H), 7.78 (d, J=15.89 Hz, 1H), 7.55 (d, J=8.31, 1H), 7.06 (m, 1H), 6.96 (m, 1H), 6.68 (m, 1H), 2.50 (s, 2H), 2.49 (s, 3H), 1.88 (m, 1H), 0.94 (d, J=6.60 Hz, 6H) ppm. .sup.13C-NMR (400 MHz, CDCl3): =194.0 (d), 150.4 (d), 145.5 (s), 137.8 (s), 131.9 (d), 130.3 (s), 128.7 (d), 127.5 (d), 126.7 (d), 45.3 (t), 30.1 (d), 22.40 (2q), 19.8 (q) ppm. GC/MS (EI): 202 (M.sup.+, 8), 187 (42), 159 (31), 145 (100), 141 (13), 131 (30), 129 (20), 128 (22), 116 (18), 115 (34).

E) 3-(4-Isobutyl-2-methyl phenyl)propanal (I)

[0058] The distilled (VI) was charged into an autoclave and isopropanol (200 ml) was added. The unsaturated aldehyde was hydrogenated over palladium (5%) on carbon at 0.5 bar hydrogen pressure. The mixture was filtrated and concentrated in vacuo. The crude product was purified by distillation over a 50 cm packed column (b.p. 116 C., 0.05 mbar) to provide the product (I) (926 g, 80% yield based on (III)).

[0059] Odor: floral, aldehydic, green, rubbery, Lilial, watery. .sup.1H-NMR (400 MHz, CDCl3): =9.88 (t, J=1.5 Hz, 1H), 7.07 (d, J=7.6 Hz, 1H), 7.0-6.95 (m, 2H), 2.98-2.93 (m, 2H), 2.79-2.74 (m, 2H), 2.46 (d, J=7.1 Hz, 2H), 2.33 (s, 3H), 1.95-1.82 (m, 1H), 0.95 (d, J=6.6 Hz, 6H) ppm. .sup.13C-NMR (400 MHz, CDCl3): =202.2 (d), 140.2 (s), 136 (s), 135.9 (s), 131.6 (d), 128.6 (d), 127.3 (d), 45.4 (t), 44.6 (t), 30.6 (d), 25.5 (t), 22.9 (q), 19.7 (q) ppm. GC/MS (EI): 204 (M.sup.+, 23), 161 (100), 147 (26), 143 (49), 119 (84), 118 (34), 117 (33), 115 (33), 105 (59), 91 (36).

EXAMPLE 2: SYNTHESIS OF 1-(DIETHOXYMETHYL)-4-ISOBUTYL-2-METHYLBENZENE (IIIB)

[0060] A mixture 85:15 of (III) and (X) (200 g, 1.13 mol) was placed in a reactor and trifluoroborane THF complex (1 g, 0.01 mol) was added. Triethyl orthoformate (200 g, 1.35 mol) was added over 20 minutes at 25-30 C. while cooling with an ice bath. The dark red reaction mixture was stirred for 10 minutes and then triethylamine (2 ml, 0.01 mol) was added and the mixture containing (IIIb) and (Xb) was distilled over a 30 cm column filled with wire mesh cylinders (23 mm) to afford pure (IIIb) (b.p 100 C., 2.6 mbar, 197 g, 69% yield)

[0061] .sup.1H-NMR (400 MHz, CDCl3): =7.46 (d, J=7.83 Hz, 1H), 6.96 (dd, J=7.58, 1.47 Hz, 1H), 6.93 (s, 1H), 5.54 (s, 1H), 3.56 (m, 4H), 2.42 (d, J=7.09 Hz, 2H), 2.35 (s, 3H), 1.84 (dt, J=13.39, 6.88(2) Hz, 1H), 1.22 (t, J=7.09(2) Hz, 6H), 0.89 (d, J=6.60 Hz, 6H) ppm. .sup.13C-NMR (400 MHz, CDCl3): =141.7 (s), 135.8 (s), 134.1 (s), 131.3 (d), 126.2 (2d), 100.2 (d), 61.3 (2t), 45.1 (t), 30.2 (d), 22.4 (2q), 18.9 (q), 15.25 (2q) ppm. GC/MS (EI): 250 (M.sup.+, 1), 206 (15), 205 (100), 177 (27), 162 (8), 134 (10), 105 (22), 103 (8), 91 (13), 57 (10), 29 (7).