A flavor compound and methods of making and using the same

Abstract

The present invention relates to a compound having a special aromatic odor, which is long-lasting and suitable for use as a flavor. The present invention also relates to a method for preparing and using the flavor compound.

Description

Technical Field

[0001] This invention belongs to the field of fragrances and relates to a compound that has a distinctive aromatic odor and a long-lasting fragrance, making it suitable for use as a fragrance. This invention also relates to methods for preparing and using the aforementioned fragrance compound. Background Technology

[0002] In the fragrance and flavor industry, the classification of floral fragrances follows the classic Ye Xinong fragrance classification system in the domestic perfumery industry. This system divides floral fragrances into four basic fragrance categories: fresh, sweet, umami, and subtle, as well as four compound fragrance categories: fresh-sweet, sweet-umami, umami-subtle, and subtle-fresh. Among them, fresh and subtle-fresh floral fragrances are characterized by good diffusion, soft aroma, and low olfactory threshold. They can impart a fresh and clean subtle fragrance effect to daily chemical products with low addition amounts. They are widely applicable to the development of fragrance formulations in areas such as fabric care, personal care, and home fragrances, and are one of the mainstream R&D directions in the industry that align with the current consumer trends of "minimalist fragrance" and "subtle fragrance".

[0003] However, the current perfumery system suffers from a severe lack of readily applicable fresh and delicate floral monomers, with the core being a limited number of classic synthetic monomers such as methyl dihydrojasmonate, lily of the valley aldehyde, and hydroxycitronellol. From the perspective of natural fragrance supply, the natural extracts of these fragrances are constrained by factors such as raw material origin, harvesting period, and extraction process, generally resulting in low yield, high cost, easy variation in aroma components, and poor stability, making it difficult to meet the requirements of large-scale industrial production. From the perspective of synthetic fragrances, existing product portfolios largely focus on strong floral monomers such as sweet and delicate notes, while commercially available fresh and delicate synthetic fragrances suffer from technical shortcomings such as limited aroma profiles, insufficient longevity, and poor compatibility with other fragrance monomers. Long-term reliance on a limited number of classic monomers for formulation not only leads to severe homogenization of end-product aromas and market olfactory fatigue, but also makes it difficult to meet the industry's stringent requirements for natural equivalent fragrances and "clean label" standards.

[0004] Therefore, developing novel floral fragrance compounds with novel structures, aroma characteristics that closely match natural fresh and subtle floral fragrances, excellent stability, long-lasting fragrance, and controllable production costs is of great practical significance for enriching the product matrix of floral fragrances, expanding the innovative dimensions of fragrance formulations, breaking through the application bottlenecks of existing fresh or subtle floral fragrances, and promoting the development of the fragrance and flavor industry towards high quality and differentiation. Summary of the Invention

[0005] The inventors of this invention unexpectedly discovered that compounds obtained by further alkylating known daphne compounds (hereinafter referred to as "compounds of this invention") possess a unique aromatic odor, which is significantly different from that of the original daphne compounds. Specifically, daphne compounds are characterized by a rich, sweet rose scent, combined with fresh berry notes and warm woody aromas, exhibiting high aroma recognition and excellent diffusion, presenting a sweet and floral fragrance. In contrast, compounds of this invention form a unique aroma profile different from daphne compounds—the sweetness is more restrained and soft, the berry notes are delicate and elegant, and the woody aroma is transformed into a velvety, warm texture, presenting an overall typical, clear, and subtle floral complex fragrance with harmonious and natural layers. At the same time, the aroma release curve of compounds of this invention differs from that of daphne compounds, exhibiting a long-lasting and subtle fragrance effect even at low addition levels, with long-lasting scent, and possessing unique advantages in compatibility with commonly used fragrance monomers, including but not limited to effectively complementing the application scenarios of daphne compounds.

[0006] Therefore, the first aspect of the present invention relates to a compound of formula I or an isomer or salt thereof:

[0007] I

[0008] Among them, R1, R2, R3, R4, and R5 are each independently selected from straight chains or branched chains C. 1-6 Alkyl groups, preferably selected from straight-chain or branched C4 groups. 1-4 Alkyl groups, more preferably selected from methyl, ethyl, n-propyl, and isopropyl, and even more preferably methyl; and

[0009] Indicates a single or double bond, and three There is at least one double bond and at most two double bonds. When there are two double bonds, the two double bonds are not adjacent to each other.

[0010] Preferably, the compound of formula I or its isomers or salts are selected from the following:

[0011] .

[0012] A second aspect of the present invention relates to a method for preparing a compound of formula I or an isomer or salt thereof, comprising the step of reacting a compound of formula II or an isomer or salt thereof with a Grignard reagent:

[0013] II,

[0014] Among them, R1, R2, R3, R4 and The definition is the same as in Equation I.

[0015] Specifically, the compound of formula II or its isomers or salts may be the following compounds of formula II-1 or II-2 or their isomers or salts:

[0016] .

[0017] More specifically, the compound of formula II or its isomers or salts are selected from the following compounds or their isomers or salts:

[0018] β-D-stakhone;

[0019] Alpha-tacrotone;

[0020] β-Turkeyone;

[0021] Tufyrenone.

[0022] The Grignard reagent may be, for example, R5-MgCl or R5-Li, wherein the definition of R5 is the same as in Formula I.

[0023] A third aspect of the invention relates to a method for obtaining or enhancing an aromatic (specifically, a light or subtle aroma) atmosphere, comprising using a compound of formula I or an isomer or salt thereof. Detailed Implementation

[0024] The isomers described in this specification include tautomers (e.g., tautomers resulting from keto-enol tautomerism of the carbonyl group of Formula I or II) and stereoisomers (e.g., E / Z isomers of the compound of Formula II). The salts described in this specification include alkoxides or oxonium salts formed from the enol configuration when keto-enol tautomerism occurs.

[0025] The preparation of compound I, or its isomers or salts, can be carried out according to the process and mechanism shown in reaction formula 1. Taking R5-MgCl as the Grignard reagent as an example, the α,β-unsaturated ketone structure in formula II undergoes a 1,4-addition with R5-MgCl to form the transition state of formula III, which is then reacted with hydrated hydrogen ions (H3O). + Compound of formula I is formed under the action of ).

[0026] The inventors of this invention unexpectedly discovered a breakthrough in the inherent rules of this type of reaction during the alkylation reaction of daumatones using Grignard reagents. In conventional understanding within the field of organic synthesis, the addition reaction of Grignard reagents with α,β-unsaturated ketones preferentially proceeds via 1,2-addition due to the significantly higher electrophilicity of the carbonyl carbon compared to the β-unsaturated carbon, generating allyl alcohol derivatives. This reaction orientation has been confirmed by extensive experimental data and authoritative literature in the vast majority of Grignard addition systems of α,β-unsaturated ketones and is a typical characteristic of this type of reaction.

[0027] The reaction system for constructing daumatone compounds in this invention does not require the introduction of special ligands, noble metal catalysts, or extreme reaction conditions. It only uses the specific reaction substrate structure of this invention and relatively mild reaction conditions to unexpectedly achieve a 1,4-addition selectivity of over 99%, generating alkylated ketone products in a near-directional manner. Even more surprisingly, this highly selective 1,4-addition product is not a trace byproduct that is difficult to avoid in traditional synthesis, but a target derivative with a special aromatic odor, whose aroma characteristics are significantly different from those of the original daumatone compounds.

[0028] Reaction 1

[0029]

[0030] As those skilled in the art will understand, the chemical formulas (e.g., formula II or III) in this specification... Indicates a single bond with unspecified direction, that is, for The double bonds are not limited to E / Z configuration.

[0031] The use of a compound of Formula I or its isomers or salts to obtain or enhance an aromatic atmosphere is known to those skilled in the art, including but not limited to placing a compound of Formula I or its isomers or salts in bath liquids or shampoos, or adding it to fabric care products (such as laundry detergent, fabric softener, fabric fragrance beads), personal care products (such as hand cream, body lotion, antiperspirant), and home fragrance products (such as air fresheners, cleaning wipes) to impart a long-lasting and harmonious aromatic scent to the aforementioned products.

[0032] The following examples are used to explain and illustrate the present invention, but should not be construed as limiting the scope of protection of the patent application.

[0033] Example

[0034] The starting reactants used in the examples were obtained as follows: β-takidomone (1-(2,6,6-trimethylcyclohex-3-enyl)but-2-en-1-one) was obtained according to the methods of Examples 2 and 5 of Chinese Patent CN102531865A; α-takidomone (1-(2,6,6-trimethyl-cyclohex-2-enyl)-2-buten-1-one) and β-takidomone (1-(2,6,6-trimethyl-cyclohex-1-enyl)-2-buten-1-one) were obtained according to the method of Example 1 of Chinese Patent CN104844431A; and dafurenone was obtained according to the method of Example 2 of Chinese Patent CN114573439A.

[0035] Other raw materials used in the examples are commercially available reagents.

[0036] The NMR spectra of the products obtained from each step of the reaction in the examples were determined by the following proton NMR spectroscopy method, using a Bruker Avance NMR spectrometer (500MHz), deuterated chloroform (CDCl3) as solvent, tetramethylsilane (TMS) as internal standard, 32 scans, 10ppm spectral width, and chemical shifts recorded using the δ-ppm scale.

[0037] The mass spectrometry of the products obtained from each step of the reaction in the examples was determined by the following gas chromatography-mass spectrometry (GC-MS): Instrument model: Agilent 8860-5977C GC-MS; Column: HP-FFAP; Injector temperature: 250℃; Carrier gas: High-purity helium (purity >99.999%); Carrier gas flow rate: 1.2 mL / min; Injection volume: 0.1 μL; Temperature program: Initial temperature 70℃ (hold for 2 min), then increase to 200℃ at 10℃ / min (hold for 20 min); Ion source: Electron impact ionization (EI); Ionization energy: 70 eV; Source temperature: 230℃; Scan mode: Full scan; Scan range: m / z 30-500; Data acquisition mode: Positive ion mode; Split ratio: 60:1; Solvent delay time: 4.5 min.

[0038] The purity of the products obtained from each step of the reaction in the examples was determined by the following gas chromatography method: using an Agilent 8860 gas chromatograph and an HP-FFAP column, the temperature was maintained at 70°C for 2 min, increased to 200°C at a rate of 10°C / min, and maintained at 200°C for 18 min. The purity was determined by the gas chromatography peak area normalization method, which is a commonly used method for determining purity in the fragrance and flavor industry.

[0039] For the evaluation of aroma effects, since they cannot be measured or evaluated using physicochemical parameters, the usual practice in the field is for professional fragrance evaluators to conduct sensory evaluations. In the embodiments of this application, the sensory evaluation of the products obtained from each reaction step was performed by a senior and authoritative fragrance evaluator with over twenty years of experience. This evaluator has extensive expertise in the sensory evaluation of fragrances and flavors, formulation development, and quality control. With solid professional theoretical knowledge and a wealth of practical experience, this evaluator possesses extremely high authority in the industry, and their evaluation conclusions have strong credibility and widespread acceptance. The fragrance evaluation experiments were conducted in a professional fragrance evaluation laboratory that meets industry standards. Before the experiment, the laboratory underwent comprehensive ventilation and purification to completely eliminate environmental odors, dust, and other interference. During the experiment, the laboratory temperature was kept constant at 22±2℃, and the relative humidity was maintained at a stable 50±5%. The room was free from direct airflow and external noise interference, and the lighting was soft and uniform, providing a standardized testing environment for the fragrance evaluation work. The experiment used standard fragrance evaluation paper (purchased from Guangzhou Zhengmao Printing Co., Ltd.) as the core evaluation medium. The fragrance sample to be tested was precisely dipped into the standard marking line on the evaluation paper. The paper, now dipped in the sample, was placed in front of the fragrance taster's nose at a suitable position, and the top notes, middle notes, and base notes of the fragrance were evaluated one by one. The aroma type, aroma intensity, aroma harmony, lasting power, and potential off-odors were systematically recorded. After each sample evaluation, sufficient olfactory recovery time was allowed before testing the next sample to avoid olfactory fatigue affecting the accuracy of the evaluation results. The evaluation method for lasting power was as follows: the standard evaluation paper was dipped into the sample to be tested, and the initial time was recorded. The paper was then placed in a standard environment and allowed to stand. Professional fragrance tasters smelled the paper at regular intervals, recording the aroma changes until no obvious target aroma remained. Parallel tests were conducted, and the average value was taken to ensure accurate results.

[0040] Example 1: Synthesis of 3-methyl-1-(2,6,6-trimethylcyclohexyl-3-enyl)but-1-one

[0041]

[0042] 3-Methyl-1-(2,6,6-trimethylcyclohexyl-3-enyl)but-1-one

[0043] 765 mL (2.30 mol) of methyl magnesium chloride solution (3 M in THF) was added to a 5000 mL four-necked flask equipped with a thermometer, mechanical stirrer, reflux condenser and drying tube. The mixture was heated to 35 °C with stirring, and 367 g (1.91 mol) of butyl dacrotone was added dropwise. The reaction temperature was controlled at 35-40 °C during the dropwise addition. After the dropwise addition was completed, the reaction was continued at 35-40 °C for 1 h.

[0044] Cool to below 30℃, add 2500g (1.28mol) of 5% sulfuric acid dropwise, stir for 30 minutes and let stand to remove the aqueous phase; wash the organic phase with 500mL of water 3-4 times, and rotary evaporate to obtain the crude product with a gas chromatographic purity of 97.98%.

[0045] The crude product was distilled under reduced pressure (<3 mmHg) in a precision distillation column, and the fraction collected at 103~108℃ was used to obtain 370 g of 3-methyl-1-(2,6,6-trimethylcyclohexyl-3-enyl)but-1-one, with a purity of 99.53% and a yield of 93.06%.

[0046] Product mass spectra (m / z): 208 (M+, 18), 123 (55), 107 (14), 91 (12), 85 (100), 81 (36), 57 (61), 43 (11), 41 (22)

[0047] Product NMR: 1H NMR (500 MHz, CDCl3) δ 5.46 (ddt, J = 9.9, 5.2, 2.2 Hz, 1H), 5.38 (ddt, J = 10.0, 3.1, 1.5 Hz, 1H), 2.45 (ddtt, J = 13.4, 6.7, 4.5, 2.1 Hz, 1H), 2.38 (dd, J = 18.0, 7.2 Hz, 1H), 2.23 (dd, J = 18.0, 6.0 Hz, 1H), 2.18 – 2.08 (m, 2H), 1.94 – 1.87 (m, 1H), 1.62 (ddt, J = 17.6, 5.4, 1.7Hz, 1H). 0.92 – 0.88 (m, 6H), 0.86 (dd, J = 6.8, 5.0 Hz, 6H), 0.81 (d, J =7.0 Hz, 3H).

[0048] Aroma of the product: Compared to the strong and full-bodied jam-like sweetness of butyl dacrotone, as well as the distinct smoky, woody and tea-based notes, the aroma of 3-methyl-1-(2,6,6-trimethylcyclohexyl-3-enyl)but-1-one is more restrained and mellow. The smoky and woody notes are also more gentle and elegant. The overall aroma has lost its flamboyance and is more delicate and refined, with a light or subtle fragrance. The fragrance lasts for up to 3 days.

[0049] Example 2: Synthesis of 3-methyl-1-(2,6,6-trimethylcyclohexyl-2-enyl)but-1-one

[0050]

[0051] 3-Methyl-1-(2,6,6-trimethylcyclohexyl-2-enyl)but-1-one

[0052] The same method as in Example 1 was used to synthesize methyl damascene as a reactant.

[0053] Product mass spectra (m / z): 208 (M+, 20), 123 (43), 91 (11), 85 (100), 81 (27), 57 (70), 41 (20)

[0054] Aroma: Compared to the intense and assertive fruity and rose notes of methyl takison, along with its interwoven smoky, woody, and green fruity undertones, 3-methyl-1-(2,6,6-trimethylcyclohexyl-2-enyl)but-1-one has a lighter and softer overall scent. Its fruity and rose notes have lost some of their sharpness, and the smoky and woody undertones are more mellow and elegant. The overall aroma is more delicate and restrained, possessing a clean or subtle fragrance profile, with a lasting scent of up to 7 days.

[0055] Example 3: Synthesis of 3-methyl-1-(2,6,6-trimethylcyclohexyl-1-enyl)but-1-one

[0056]

[0057] 3-Methyl-1-(2,6,6-trimethylcyclohexyl-1-enyl)but-1-one

[0058] The same method as described above was used to synthesize β-takitone as a reactant.

[0059] Product mass spectra (m / z): 208 (M+, 4), 152 (15), 151 (100), 123 (49), 81 (35), 41 (14)

[0060] Aroma of the product: Compared to the characteristic full-bodied and sweet rose fruit scent of β-takison, along with the accompanying notes of ripe plum, blackcurrant and smoky candied fruit, 3-methyl-1-(2,6,6-trimethylcyclohexyl-1-enyl)but-1-one expresses a more mellow rose scent and a more elegant layer of fruity aroma, presenting a more transparent and soft fragrance quality. While retaining a rounded feel, it has shed the original strong tension, with a light or delicate fragrance profile and a lasting scent of up to 3 days.

[0061] Example 4: Synthesis of 3-methyl-1-(2,6,6-trimethylcyclohexyl-1,3-dienyl)but-1-one

[0062]

[0063] 3-Methyl-1-(2,6,6-trimethylcyclohexyl-1,3-dienyl)but-1-one

[0064] Synthesized using datumene ketone as a reactant, following the same method as described above.

[0065] Product mass spectra (m / z): 206 (M+, 20), 150 (11), 149 (100), 122 (14), 121 (93), 120 (12), 105 (39), 91 (29), 85 (32), 79 (15), 77 (18), 57 (42), 41 (16)

[0066] Aroma: Compared to the explosive floral and fruity notes of daumarenone, 3-methyl-1-(2,6,6-trimethylcyclohexyl-1,3-dienyl)but-1-one retains its natural, authentic complex of rose, plum, berry, and tobacco, but presents it with a more elegant and transparent quality. The rose scent loses its intensity, the freshness of the berries and plum becomes more prominent, and the tobacco base also transforms into a soft finish, presenting an overall serene and elegant character with a lasting fragrance of up to 3 days.

Claims

1. A compound of formula I or an isomer or salt thereof: I in, R1, R2, R3, R4, and R5 are each independently selected from straight chains or branched chains C. 1-6 Alkyl groups, preferably selected from straight-chain or branched C4 groups. 1-4 Alkyl groups, more preferably selected from methyl, ethyl, n-propyl, and isopropyl, and even more preferably methyl; and Indicates a single or double bond, and three There is at least one double bond and at most two double bonds. When there are two double bonds, the two double bonds are not adjacent to each other.

2. The compound of formula I according to claim 1, or an isomer or salt thereof, is selected from the following compounds or isomers or salts thereof: 。 3. A method for preparing a compound of formula I according to claim 1 or 2, or an isomer or salt thereof, comprising the step of reacting a compound of formula II, or an isomer or salt thereof, with a Grignard reagent: II, Among them, R1, R2, R3, R4 and The definition is the same as in claim 1 or 2.

4. The method according to claim 3, wherein the compound of formula II or its isomer or salt is a compound of formula II-1 or formula II-2 or its isomer or salt: 。 5. The method according to claim 3, wherein the compound of formula II or an isomer or salt thereof is selected from the group consisting of: ； ； ； 。 6. The method according to any one of claims 3-5, wherein the Grignard reagent is R5-MgCl or R5-Li, wherein R5 is defined as in claim 1 or 2.

7. A method for obtaining or increasing an aromatic atmosphere, comprising using a compound of formula I or an isomer or salt thereof.

8. The method according to claim 7, wherein the aromatic atmosphere is a light or subtle aromatic atmosphere.

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