MXPA00011236A - Novel fragrance compounds - Google Patents

Abstract

4,8-cyclododecadienyl ketones having formula (I), in which R has up to 5 carbon atoms, are novel compounds exhibiting woody/amber odour characteristics which find use in perfumes and in perfumed products.

Description

"Ketones", coirto ^ 'is discussed in more detail later. In particular, the preferred compounds of the invention comprise a mixture of the illustrated isomers-ß- Figure 3. The ketones of the invention exhibit wood / amber / alkylated odor characteristics and thus can be used as such for impart, reinforce or improve the odor of a wide variety of products, can be used as a component of a perfume (or fragrance composition) to contribute to its odor character to the full smell of this perfume. For the purposes of this invention, a perfume is proposed to mean a mixture of fragrance materials, if desired, mixed with or dissolved in a suitable solvent or mixed with a solid substrate, which can be used to impart a desired odor to the skin and / or any product for which a pleasant smell is indispensable or desirable. Examples of these products are: fabric washing powders, washing liquids, fabric softeners and other fabric care products; detergents and household cleaning products, scrubbing and disinfection; air fresheners, room sprays and perfumed pads; soaps, bath and shower gels, shampoos, hair conditioners and other personal cleansing products; cosmetics such as creams, ointments, cologne waters, pre-shaving lotions, after-shave lotions, for skin and others, talcum powder, deodorants and body perspirants, etc. Other fragrance materials that can be advantageously combined with a ketone according to the invention in a perfume are for example natural products such as extracts, essential oils, absolutes, resinoids, resins, concretes, etc., but also synthetic materials such as hydrocarbons. , alcohols, aldehydes, ketones, ethers, acids, esters, acetals, ketals, nitriles, etc., including saturated and more saturated compounds, aliphatic, carboxylic and heterocyclic compounds. These fragrance materials are mentioned, for example, in S. Arctander, Perfume and Flavor Chemicals (Montclair, NJ, 1969), in S. Arctander, Perfume and Flavor Materials of Natural Origin (Elizabeth, NJ, 1960) and in "Flavor and Fragrance Materials - 1991", Allured Publishing Co. Wheaton, III, USA.

The examples of fragrance materials that may be used in combination with a ketone according to the invention are: geraniol, geranyl acetate, linalool, linalyl acetate, tet rahydrolmalol, citronellol, citronellyl acetate, dihydromyrcenol, dihydromyrcenyl acetate, tetrahydromyrcenol, terpineol, terpinyl acetate, nopol, nopyl acetate, 2-phenyl-ethanol, 2-phenylethyl acetate, benzyl alcohol, benzyl acetate, benzyl salicylate, styralyl acetate, benzyl benzoate, amyl salicylate, dimethylbenzyl carbinol, ricloromet and l-phenylcarbonyl acetate, p-tert-butyl-cyclohexyl acetate, isononyl acetate, vetyveryl acetate, vetyverol, a-hexylcinnamaldehyde, 2-methyl-3- (p-) tert-butylphenyl) propanal, 2-met il-3- (p-isopropyl phenyl) propanal, 3- (p-ter-but i 1 phenyl) propanal, 2,4-dimethylcyclohex-3-enylcarboxaldehyde, tr iciclodecenyl, tricyclodecenyl propionate, 4- (4-hydroxy-4-methylpentyl) -3-cycl ohexenocarboxaldehyde, 4- (4-methyl-3-pent-enyl) -3-c-clohexene-carboxaldehyde, 4-acetoxy-3 -pent i 1-tetrahydropyran, 3-carboxymethyl-2-pentyl-cyclopentane, 2-n- heptylcyclopentanone, 3-methyl -2- S &? J- SS .. pentyl-2-c-clopenteno-na, n-decendal, n-dodecenal, 9-decenol-1, phenoxyethyl isobutyrate, fen-lacetaldehyde-dimethyl, ketal, phenylacetaldehyde-dietary, geranyl-nitryl, citronellyl nitrile cedaryl acetate, 3-isocamf ilcyclohexanol, cedrile methyl ether, isolongifolanone, aubepin nitrile, aubepin, heliotropin, coumarin, eugenol, vanillin, diphenyl oxide, hydroxy itronellal, ionones, methionines, isomethyl ionones, ironones, cis-3-hexenol and esters thereof, indax musks, tetralin musks, isochroman musks, macrocyclic ketones, macrolactone musks, ethylene brasilate. The solvents that can be used for perfumes containing the ketones according to the invention are for example: ethanol, isopropanol, ethylene glycol monomethyl ether, dipropylene glycol, diethyl phthalate, triethyl citrate, isopropyl myristate, etc. The amounts in which a ketone according to the invention can be used in perfumes or in products to be perfumed can vary within wide limits and depend inter alia on the nature of the product, the nature and the nature of the product. quality of the other components of the perfume in which the ketone is used and of the desired olfactory effect. Therefore, it is only possible to specify broad limits, which, however, provide sufficient information for the person skilled in the art to be able to use the ketone according to the invention for its specific purpose. In perfumes, an amount of 0.01% by weight or more of a ketone according to the invention will generally have a clearly perceptible olfactory effect. Preferably, the amount is 0.1-80% by weight, more preferably at least 1%, the amount of the ketone according to the invention present in products will generally be at least 10 ppm by weight, preferably at least 100 ppm, more preferably at least 1000 ppm. However, levels of up to about 20% by weight can be used in particular cases, depending on the product to be perfumed. In a further aspect, the invention thus provides a fragrance comprising a ketone of the invention in an olfactory effective amount. The invention also covers a product perfumed comprising a ketone of the invention.

Ketones of the invention can be produced from the aldehyde, 4,8-c? Clododecad? Ene-1 -carbaldehyde (referred to herein as QRM 2815) by reaction with a range of Grignard reagents (RMgX), followed by oxidation with chromic acid, as illustrated in Figure 1. A range of ketones according to the invention has thus been produced, with the side chains R and odor properties as follows: R Number Description of chemical name of QRM odor Methyl 2828 Not selected l- (4,8-cyclododecadienyl) -1- ethanone Ethyl 2843 Cedar wood, l- (4,8-amber, pepper cyclododecadienil) -1- propanone n- propyl 3101 Wood, l- (4,8- cyclododecadienyl musk) -1- butanone Iso2885 Wood, amber l- (4,8-propyl cyclododecadienyl) -2- methy1-1-propanone n-butyl 3102 Not selected l- (4,8-cyclododecadienyl) -1- pentanone Sec- 3056 Amber / wood, l- (4,8-butyl with fruit smell cyclododecadienyl) -2- methyl-1-butanone 2- 2924 Amber / wood, l- (4,8-propenyl cyclododecadienyl cyclo) -2- buten-1-one The side chain R in this manner can be a straight or branched chain, saturated or unsaturated. R has these 5 carbon atoms, resulting in a molecule having at least 18 carbon atoms. Molecules with more than 18 carbon atoms tend to have a vapor pressure that is too low for the molecule to have an odor value. Conveniently isopropyl magnesium chloride is used as the Grignard reagent to produce the QRM ketone 2885 in this manner, with other Grignard reagents (RMgX) which is used as is analogously appropriate to produce other ketones. Ketones can exist in different isomeric forms, and the invention covers each isomeric form alone and mixtures of different isomeric forms. The preparative technique used has a major influence on the relative proportions of the different isomeric forms. The QRM 2815 aldehyde can be produced from 1, 5, 9-cyclododecatriene, which is a cheap and easily accessible starting material, by the reaction shown in Figure 2, in which the cyclododecatene is converted to monoepoxide cyclododecat rieno by reaction with an acid followed by catalytic isomerization. The reaction is described in more detail later. An alternative preparative route to the aldehyde comprises the hydroformylation of 1,5,9-cyclododecatiene by reaction with hydrogen and carbon monoxide in the presence of a catalyst such as rhodium catalyst. Of the ketones of the invention produced and tested so far, QRM 2885 (R = iso-propyl) is currently favored as a fragrance material since it has good odor characteristics and a good balance of initial impact and substantivity properties. . The compound is also predicted to be biodegradable, but this has not been proven yet. The QRM 2885 is presented in two geometric isomers. When the QRM 2815 aldehyde is prepared by the route shown in Figure 2, the QRM 2885 is produced as an isomeric mixture of (Z, E) -4, 8-cyclododecadienyl-2-met il-1-propanone [isomer A] (89%), and (E, Z) -4, 8-cyclo-dodecadienyl-2-methyl-1-propanone [isomer B] (7%), as shown in Figure 3. However, when the aldehyde is prepared by the hydroformylation route described previously, the two isomers were found to be present in approximately equal amounts. The two isomers are preferably present in a ratio of A: B in the range of 95: 5 to 5:95 by weight, more preferably in the range of 90: 5 to 40:60, A: B by weight and more preferably, in the range of 55:45 to 45:55, A: B by weight. Each of the geometric isomers of QRM 2885 exists as two optical isomers and the ketones of the invention include mixtures of optical isomers. The olfactometry by glc indicated that both isomers have an amber odor of wood, with the isomer of (Z, E) -4, 8 -c? Clododecad? In? L-2-met? L-l-propanone that seems to have a dryer smell quality. Excellent performance was exhibited on a wet and dry fabric conditioner fabric, by QRM 2885 against the standards of known fragrance materials, Cyclisone (Cyclisone is a registered trademark) of Quest International and Iso E Super (Iso E super is a registered trademark) of Acedsa. The QRM 2885 ketone is useful as a fragrance material both as an isomeric mixture and as a preparation, and as individual isomers.

The invention was further described, by way of illustration, in the following examples and with reference to the accompanying figures in which: Figure 1 illustrates the ketone production from 4,8-c? Clododecad? Ene-l-carbaldehyde; Figure 2 shows a reaction scheme for the production 4, 8 -c? clododecad? ene-1-carbaldehyde; and Figure 3 shows the two geometric isomers of 1- (4,8-cyclododecadienyl) -2-met-1-propanone (QRM 2885).

ETemplo 1 Synthesis of l- (< -cyclododecadienil) -2-met íl-l-propanone (QRM 2885) a) Synthesis of 4,8-C? clododecad? ene-1-carbaldehyde (QRM 2815) 4,8-c? Clododecad? ene-carboxaldehyde (QRM 2815) was produced from 1,5,9- cyclododecat rino by the reaction illustrated in Figure 2. The 1, 5, 9-c? clododecat peno ((1) in Figure 2) was reacted with an equivalent of met a-chloroperoxybenzoic acid (m-CPBA) in the presence of CH2Cl2 to give 1,5,9-cyclododecane monoepoxide ((2) in Figure 2). This is consistent with the reported relative susceptibility of E-bonds to electrophilic reagents (H. Nozaki, S. Kato, R. Noyoru, Can. J. Chem., 44, 1021, (1966)). The isomerization of this epoxide by a rearrangement catalyzed with Mgl2 in the presence of diethyl ether (German Patent No. 1,075,601). It gave the cyclododecadienone (referred to herein as QRM 2814) as a mixture of isomers, 4-Z-8-E- (87%) and 4-E-8-Z- (12%) (F. Lombardo, RA Ne Mark, E. Kariv-Miller J Org. Chem. 56.2422, (1991)). In order to retain this known ratio of isomers, therefore, the homologation of the ketone QRM 2814 to 4,8-cyclododecadienylcarboxaldehyde (QRM 2815) was carried out by the reaction with lithium tripolylsilyldiazomethane (K. Miwa, T. Aoyama, T. Shiop Synlett, 109, (1994)), in the presence of excess dusopropylamine, to give the enamma ((3) in Figure 2), which readily hydrolyzed the aldehyde, QRM 2815, only by stirring on wet silica. Considering the matter in more detail, the monoepoxide of 1, 5, 9-c? Clododecatriene [100 g; 0.56 mol] in Et2Ü (300 ml), and magnesium iodide [10 g; 0.036 mol] was added. The mixture was placed in a 1-liter Buchi autoclave and heated to 70 °, with stirring, monitoring the progress of the reaction by glc [SE 54; 100-250 ° to 4 ° C / m? N].

Epoxide Reaction mixture 16.408 mm (94%) 15.753 min (12%) 15.858 min (87%) After cooling, the reaction mixture was partitioned (Et2? / H20), and the organic layer was separated, washed, dried and flash chromatographed [silica: 90% hexane, Et2? 10%] to give a colorless oil (89.2 g, 89%), which was used directly in the next stage. Add? -Pr2NH [80 g; 0.79 mol] to tetrahydrofuran (THF) (100 ml), cooled to -30 ° C, and added dropwise by n-BuLi syringe [40 ml of 2.5 M, 0.1 mol], under N2. Add dropwise (tpmethylsilyl) diazo ethane (TMSCHN2) [50 ml; 1.9 M in hexane; 0.095 mol] to this solution of lithium dusopropylamide (LDA) at -70 ° C. After complete addition, a solution of 4,8-c? Clododecad? Ene-l-one [14.2 g; 0.08 mol] in Anhydrous THF (50 ml), the reaction mixture was allowed to stir for 1 hour at -70 ° C, then allowed to reach room temperature. Subsequently, it was refluxed for 3 hours. Most of the THF was removed in vacuo, added to Et20 (300 mL), and the reaction mixture was poured into ice water. After extraction in Et2 ?, the solvent was removed, the residue redissolved in ethyl acetate (300 ml), and added on silica gel (100 g), together with H20 (1 ml). The mixture was stirred overnight under N2, the mixture was concentrated in vacuo, then charged onto a short column of silica. Flash chromatography using a mixture of hexane (90%) and Et20 (10%) as eluent gave the 4,8-cyclododecadiene-carboxaldehyde (QRM 2815) as a colorless oil (14.0 g). b) Synthesis of 1- (4,8-Cyclododecadienyl) -2-met il-1-propanone (QRM 2885) The reaction is shown in Figure 1, where R is isopropyl. 4,8-cyclododecadiene-carboxaldehyde (QRM 2185) [14.0 g; 0.072 mol] in THF (50 ml), and isopropyl-magnesium chloride [36] ml; 2.0 M in Et20, 0 072 mol] was added dropwise with stirring under N2. The reaction mixture was stirred for 30 minutes, most of the solvent was removed and the residue was rapidly cooled with saturated ammonium chloride solution, and then partitioned (Et20 / H20). The organic layer was separated, washed and dried over MgSO4. The solvent was removed and the residue was chromatographed [50% silica, 50% hexane] to give 1- (4, 8-c? Clododecad? In? L) -2 -met? L-1- Propanol (11.1 g, 65%) as a colorless oil. This material was dissolved in Et20 (150 ml), and chromic acid [from sodium dichromate (10 g), H2SO4 (10 ml) and H2O (50 ml)] was added dropwise with stirring. The reaction mixture was partitioned between Et20 and H2O, and the organic layer was separated, washed and dried. Chromatography [silica; Et2? 10%, hexane 90%] gave a colorless oil which was distilled by short route, boiling at 125 ° C at 3 mbar, 6.3 g (58%). Glc [SE54; 100-250 ° C at 4 ./min] 22.512 min (7%) M + 234, 23.118 mm (89%) M + 234. The material produced was an isomeric mixture of (Z, E) - 1- (4, 8-c? Clododecad? In? 1) -2- methanol-1-propanone (89%), and (E, Z, -1- (4,8-cyclododecadienyl) -2-met? l-1-propanone (7%), as shown in Figure 3 As noted above, other ketones according to the invention can be produced from the QRM 2815 aldehyde by reaction with a range of Gpgnard reagents, followed by oxidation, as generally illustrated in Figure 1.

EXAMPLE 2 Experiments were carried out to test the stability and substantivity of l- (4,8-cyclododecadienyl) 2-met l-1-propanone (QRM 2885) in the form of isomeric mixture produced as described in Example 1 a) Stability test in the product Performance in QRM 2885 was compared with that of two known fragrance materials, Cyclisone (Cyclisone is a Registered Trademark) of Quest International and Iso E Super (Iso E Super is a Registered Trademark) of Acedesa. The three fragrance materials were dosed individually in an interval selected from product bases (listed below) and subjected to accelerated storage. The assessment for olfactory and color stability was carried out by a panel of perfumers and synthetic chemists after 4 and 12 weeks of storage. The product bases and the fragrance dose in percent w / w used for this study were: Alcohol (1%) Soap base No. 2 (0 5%) Shampoo (3.0%) Citric acid toilet cleaner (0.5%) Fabric conditioner - Hamburg Ester Quaternary (HEQ) (0.3%) Heavy Duty Laundry Liquid (HDLL) (Maplyn) (0.3%) Anti-Perspirant (Aluminum Hydrochloride (ACH) Roll-On) (3.0%) Laundry powder from tet raacet i let ilendiamine (TAED) / Perborate (0.3%) Laundry powder (Surf) (0.5%).

In addition, samples of QRM 2885 in HEQ tissue conditioner and No. 2 soap base were assessed for chemical stability after 12 weeks of accelerated storage at 37 ° C. The extraction was carried out by normal laboratory methods. The HEQ samples were stored in 15 ml glass bottles and the soaps were stored as small bars in a wax paper package.

The conclusions were as follows: 1. The QRM 2885 was rated as having a "good" "good / moderate" performance in alcohol, soap, shampoo, tissue conditioner, anti-perspirant and laundry powder Surf after 12 weeks of storage at 37 ° C (37 ° C) C / 70% relative humidity for laundry test). A "moderate performance" in TAED / perborate laundry powder was also recorded. 2. QRM 2885 was rated as having better performance / stability than both Cyclonone and Iso E Super in soap, tissue conditioner, TAED / perborate laundry powder and Surf laundry powder. 3. In the other product bases (ie alcohol, shampoo and anti-perspirant), QRM 2885 performance was considered to be equivalent and better than either Cyclisone or Iso E Super. 4. QRM 2885, Cyclisone and Iso E Super all exhibited "poor" stability / performance in citric acid and HDLL toilet cleaner. 5. The chemical stability of QRM 2885, after 12 weeks of storage at 37 ° C. remaining Tissue Conditioner (HEQ) 66% Soap Base No. 2 100% b) Fiber substantivity test The same three fragrance materials were evaluated for their fiber-based substantivity in plush fabric from the HEQ tissue conditioner base. All the fragrance ingredients were dosed at 0.25% w / w at a regular concentration of HEQ tissue conditioner. The tissue conditioner was then dosed 3 g / 1 of Water in the tergotometer was mixed and two pieces of plush fabric were added and shaken at 100 rpm for 10 minutes. The fabrics were then evaluated dried on line and moistened by 5 creative perfumers. The results of this fiber mass assessment showed that QRM 2885 has good fiber quality in both wet and dry plush with the QRM 2885 which performs better than the Ciclosona and Iso E Super standards in three of the five valuations.

Example 3 A rhodium catalyst, Rh-42, was dissolved [Carbonylhydpdotris (tp-phenylphosphine) rod (I)] in cis, trans, t rans-c? Clododeca-1, 5, 9-trilene at a concentration of 0.5 molar percent and the resulting solution is rapidly stirred under an atmosphere of CO / H2 1: 1 by volume at a pressure of 1 MPa for 45 hours. The temperature was maintained at 70 to 80 ° C and the reaction was monitored by glc. The crude reaction mixture was passed through a cloth film evaporator to remove the rhodium catalyst and 4,8-cyclododecadiene-1-carbaldehyde.

I separate by distillation. The yield of 4,8-c? Clododecad? Ene-1 -carbaldehyde was 55%. This aldehyde was then converted to l- (4,8-cyclododecadieml) -2-met l-1-propanone by reaction with isopropylmagnesium chloride as described in part (b) of Example 1. The produced material contained about 91% of an isomeric mixture of (Z, E) -1- (4,8-cyclododecadienyl) -2 -met-l-1-propanone, and (E, Z) -1- (4,8-cydododecadienyl) ) -2-methyl-1-propanone, these two isomers that are present in approximately normal amounts.

Claims (10)

1. CLAIMS 1. A 4, 8-c? Clododecad? In? L-ketone, which has the formula shown below wherein R is an alkyl group having up to 5 carbon atoms.
2. 2. A ketone according to claim 1, wherein R is iso-propyl
3. 3. A ketone according to claim 2, comprising a mixture of geometric isomers (Z, E) -4, 8-cyclododecadieni 1-2 -methyl 1- 1 -propanone and (E, Z) -4,8-cyclododecadiem 1-2 -met-1-l-propanone.
4. 4. A method for making the compound according to any of claims 1 to 3, which comprises reacting 4,8-c? Clododecad? Ene-1-carbaldehyde with a Grignard reagent, followed by oxidation.
5. 5. A method of claim 4, wherein 4,8-c? Clododecad? Ene-1-carbaldehyde is prepared by reaction of 1, 5, 9-c? Clododecatrone with a peroxyacid to form monoepoxide of 1, 5,9- ciclododecat r íeno followed by catalysed isomerization.
6. 6. A method according to claim 4, wherein 4,8-cyclododecadiene-1-carbaldehyde is prepared by hydroformylation of 1,5,9-cyclododecane with carbon monoxide and hydrogen. .
7. A perfume comprising a ketone according to any of claims 1 to 3, in an olfactory effective amount.
8. 8. A perfume according to claim 7, wherein the ketone is present in a cation of at least 0.01% by weight.
9. 9. A perfume according to claim 8, wherein the ketone is present in an amount in the range of 0.1 to 80% by weight.
10. 10. A perfumed product comprising a ketone according to any of claims 1 to 3 or a perfume according to any of claims 7, 8 or 9.