ORGANIC COMPOUNDS

Abstract

The use of a compound represented by the formula I

##STR00001##

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,
as perfume ingredients in personal care and household care products.

Claims

1. A perfume ingredient being 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; as a perfume ingredient.

2. The perfume ingredient according to claim 1, wherein the compound has muguet odour characteristics.

3. A compound represented by 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 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, or 4-(4-(tert-butyl)phenyl)-3-methylbutanal.

4. A pro-perfume, adapted to release the compound represented by 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.

5. A perfume composition comprising a compound represented by the formula I ##STR00021## 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 ##STR00022## 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.

6. A perfume composition according to claim 5 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?.

7. A perfume composition according to claim 5 comprising one or more additional fragrance ingredients selected from: 3-(4-isobutyl-2-methylphenyl)propanal and 3-(4-(tert-butyl)-2-methylphenyl)-2-methylpropanal.

8. A personal care or household care composition comprising a compound represented by the formula I ##STR00023## 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.

9. A personal care or household care composition according to claim 8, further comprising enzymes.

10. A personal or household care composition according to claim 8 which is a textile treatment product.

11. A personal or household care composition according to which is a detergent composition.

12. 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 represented by the formula I ##STR00024## 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 ##STR00025## 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 selectively excluding from said fine fragrance or consumer product 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?.

13. The pro-perfume of claim 4, which is an aminal and/or enamine of the compound represented by the formula I.

14. A personal care or household care composition comprising a perfume composition according to claim 5.

15. A personal care or household care composition comprising a perfume composition according to claim 6.

16. A personal care or household care composition comprising a perfume composition according to claim 7.

Description

EXAMPLE 1

4-(4-(tert-Butyl)phenyl)butanal

[0100] A mixture comprising this compound was described in NL 7502553 having a pleasantly sharp, pungent odor, useful for perfumes.

##STR00008##

1) A suspension of KOtBu (8.85 g, 79 mmol) in THF (150 ml) was cooled to 0? C. and methoxymethyl triphenylphosphoniumchloride (27.00 g, 79 mmol) was added in two portions. The mixture was stirred for 10 min and a solution of 3-(4-(tert-butyl)phenylpropanal (Bourgeonal; 10.00 g, 52.6 mmol) in THF (50 ml) was added dropwise. The mixture was stirred for another 1.5 h and poured into water (80 ml, containing a few drops of HCl) and extracted twice with pentane (100 ml). The combined organic phases were washed with water (100 ml) and brine (100 ml), dried (MgSO.sub.4) and concentrated in vacuo. The residue was taken up in pentane (50 ml), filtered and concentrated again in vacuo to yield crude 1-(tert-butyl)-4-(4-methoxybut-3-en-1-yl)benzene (13.04 g) as a yellowish oil.
2) This oil (11.27 g) was added to a mixture of THF (150 ml) and 2M HCl (39 ml) and the heated to reflux temperature for 2 h. The solution was then poured into ice cold aq. 2M NaOH and extracted with MTBE (2?100 ml). The combined organic phases were washed with water (100 ml) and brine (100 ml), dried (MgSO.sub.4) and concentrated in vacuo. The residue was purified by chromatography on silica gel (eluent hexane:MTBE 50:1) to yield 4-(4-(tert-butyl)phenyl)butanal (7.33 g, 70%) as a colorless oil.

[0101] .sup.1H-NMR (CDCl.sub.3, 400 MHz): 9.75 (t, J=1.7 Hz, 1H), 7.32-7.29 (m, 2H), 7.11-7.09 (m, 2H), 2.62 (t, J=7.8 Hz, 2H), 2.44 (dt, J=7.8 Hz, 1.7 Hz, 2H), 1.98-1.91 (m, 2H), 1.31 (s, 9H) ppm.

[0102] Odor description: fatty, waxy, floral, weak in comparison to 4-(4-(isobutyl)phenyl)butanal and 4-(4-isobutyl-2-methylphenyl)butanal

EXAMPLE 2

4-(4-(Isobutyl)phenyl)butanal

[0103] The material was prepared according to example 1 using 3-(4-(isobutyl)phenylpropanal as starting material.

[0104] .sup.1H-NMR (CDCl.sub.3, 400 MHz): 9.74 (t, J=1.7 Hz, 1H), 7.09-7.04 (m, 4H), 2.62 (dd, J=7.4 Hz, 7.4 Hz, 2H), 2.46-2.41 (m, 4H), 1.98-1.91 (m, 2H), 1.84 (sept, J=6.8 Hz, 1H), 0.89 (d, J=6.8 Hz, 6H) ppm.

[0105] Odor description: fruity, aldehydic, floral, green, fatty, strong

EXAMPLE 3

Synthesis of 4-(4-Isobutyl-2-methylphenyl)butanal

[0106] ##STR00009##

[0107] 3-(4-Isobutyl-2-methylphenyl)propanal was obtained as described in patent application PCT/EP2014/059427, which is hereby incorporated by reference.

[0108] 3-(4-Isobutyl-2-methylphenyl)propanal was converted according to the procedure described in example 1 to yield 4-(4-isobutyl-2-methylphenyl)butanal as a colourless oil.

[0109] .sup.1H-NMR (CDCl.sub.3, 400 MHz): 9.76 (t, J=1.7 Hz, 1H), 7.03-6.99 (m, 1H), 6.92-6.89 (m, 2H), 2.61 (dd, J=7.8 Hz, 7.6 Hz, 2H), 2.48 (dt, J=7.6 Hz, 1.7 Hz, 2H), 2.40 (d, J=7.2 Hz, 2H), 2.27 (s, 3H), 1.94-1.86 (m, 2H), 1.83 (sept, J=6.8 Hz, 1H), 0.89 (d, J=6.8 Hz, 6H) ppm. .sup.13C-NMR (CDCl.sub.3, 100 MHz): 202.4 (s), 139.6 (s), 136.6 (s), 135.5 (s), 131.2 (d), 128.7 (d), 126.7 (d), 45.9 (t), 43.5 (t), 32.1 (t), 30.2 (d), 22.6 (t), 22.5 (2q), 19.3 (q) ppm. MS (EI, 70 eV): 218 (M.sup.+, 10), 174 (28), 159 (100), 145 (15), 133 (17), 119 (88), 105 (25), 91 (21), 77 (9), 55 (12), 41 (17).

[0110] Odor description: floral, green, lilial, silvial, strong

EXAMPLE 4

In Vitro Metabolism Study. A Comparison of Compounds of the Present Invention and Lilial?

[0111] Cryopreserved hepatocytes from male rats (Sprague Dawley; Lifetechnologies) were defrozen, washed in Cyropreserved Hepatocytes Recovery Medium (CHRM; Lifetechnologies) and suspended in Williams E Medium (WEM; Lifetechnologies). Lilial?, or the compounds of the present invention (final concentration: 100 ?M) were added to the cells (1?106 viable cells/ml) and suspensions were incubated up to 4 hours at 37? C. on a shaker in duplicate. Metabolism of testosterone was monitored as positive control. Decrease of the test compounds and formation of the corresponding benzoic acid derivative was determined by GC-MS analysis of methyl esters formed after derivatisation with trimethylsilyl diazomethane (Sigma-Aldrich) in methanol. The test compounds react with diazomethane yielding a methyl ketone which was used for the quantification of Lilial? and the compound of formula (I). Metabolism was stopped with ice cold 1 M HCl, samples were extracted with tert-butyl methyl ether (MTBE) and analysed by GC-MS. Incubations containing testosterone as control were also stopped with ice cold 1 M HCl, centrifuged to separate the cells, filtrated and the decrease of testosterone analysed by LC-MS. To quantify decrease of the test substances and formation of benzoic acid metabolites, calibration curves of reference materials Lilial? and the compounds of the present invention, tert-butyl benzoic acid (Fluka) was prepared in hepatocyte incubation medium and analysed like the hepatocyte samples.

[0112] A rapid decrease of testosterone as positive control was observed indicating that the hepatocytes were metabolically active. The compounds of the present invention and Lilial? were metabolised rapidly in rat hepatocytes and no residual compound except for 2% with one compound was measured after 4 h. Whereas tert-butyl benzoic acid was detected as metabolite of Lilial? (3.4-3.9 ?M) no benzoic acid derivatives were formed from compounds of the present invention (Table 1). Limit of detection was <1 ?M.

[0113] Table 1 (below), shows the concentrations of Lilial? and compounds of the present invention as well as corresponding benzoic acid metabolites in rat hepatocytes within 4 hours incubation. Initial test concentration at 0 hours incubation was 100 ?M.

[0114] It is clear from the data presented in Table 1 that the ortho substituent at the benzene ring of the compounds of the present invention and/or the aldehyde functionality being butanal does affect the formation of the corresponding benzoic acid derivative in vitro. Since benzoic acid derivatives such as tert-butyl benzoic acid from Lilial? cause reproductive toxicity in male rats, these toxic effects in male rats are prevented by the ortho-substituent of the compounds of the present invention, and are reduced by the aldehyde functionality being butanal.

[0115] Beta oxidation should lead to 4-substituted phenyl acetic acid derivatives but not to the corresponding benzoic acid. Indeed the formation of the benzoic acid is reduced to low levels in comparison with Lilial?.

TABLE-US-00001 TABLE 1 Residual conc. Benzoic acid concentration Test compound (?M) derivative (?M) [00010] 0 [00011] 3.5-3.9 [00012] 0 [00013] 1.4 [00014] 0.7 [00015] 1.3 [00016] 0.2 [00017] 0.5

[0116] In a further experiment, it was demonstrated, that 4-(4-isobutyl-2-methylphenyl)butanal (compound of example 3) does not provide the formation of the corresponding esters with Coenzym A. Therefore, it can be assumed, that no benzoic acid derivative of that compound is formed.