A green-type fragrance compound and methods of making and using the same

Abstract

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

Description

Technical Field

[0001] This invention belongs to the field of fragrances and relates to a compound that has a distinctive green aromatic odor with 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] Green aroma fragrances are a type of fragrance with a fresh, invigorating, and grassy scent. Their aroma mimics the natural scent of freshly mowed lawns, dewy grass in the morning, and wet grass after rain. They can bring people a refreshing, relaxing, and nature-inspired sensory experience. They are widely used in various fields such as daily chemicals, food, and tobacco, and are one of the most in-demand fragrance types in the fragrance industry.

[0003] Currently, existing green aromatic fragrances are mainly divided into two categories: naturally extracted and chemically synthesized. Natural green aromatic fragrances are mainly extracted from plants through methods such as distillation, cold pressing, and solvent extraction, such as leaf alcohol, leaf aldehyde, and bergamot oil. Their aroma is natural and pure, but they suffer from drawbacks such as limited raw material sources, complex extraction processes, high production costs, low yields, poor aroma stability, and short retention time, making it difficult to meet the needs of large-scale industrial production and practical applications. Chemically synthesized green aromatic fragrances, on the other hand, have advantages such as readily available raw materials, low production costs, high yields, and good aroma stability, making them the mainstream products in the market. However, most existing chemically synthesized green aromatic fragrances suffer from a single aroma, impure green aroma, off-flavors or a cloying sweetness, and a short retention time. In addition, some synthesis processes have problems such as harsh reaction conditions (e.g., high pressure, high temperature), high energy consumption, high pollution, complex reaction steps, and low product yields, which limit their application scope.

[0004] With the improvement of people's living standards and the upgrading of consumption, the market has increasingly higher requirements for the quality of green aroma fragrances. These fragrances not only need to be fresh, natural, pure, and free of off-flavors, with long-lasting aroma, but also require green, environmentally friendly, simple, and low-cost preparation processes that can be widely adapted to different application scenarios. Therefore, developing a green aroma fragrance compound that is pure, long-lasting, stable, has a simple, environmentally friendly, and low-cost preparation process, and has a wide range of applications has significant practical importance and market prospects. Summary of the Invention

[0005] The inventors of this application, referring to the method in CN101125805B, used cyclohexenylethyl ketone compounds as starting materials to prepare α,β-unsaturated ketones. The first step of this reaction is to perform an addition reaction of the ketone carbonyl group of the starting material with a Grignard reagent to generate an enol salt intermediate. During this process, the inventors of this application discovered that the reaction simultaneously generates a small amount of byproducts. After purification, these byproducts were identified as tertiary alcohol compounds. The tertiary alcohol compound was then subjected to an esterification reaction with a carboxylic acid or anhydride, unexpectedly yielding a green fragrance compound. This product has a significantly higher aroma intensity than existing green fragrances, and possesses a pure, grassy aroma with strong layers of complexity.

[0006] The tertiary alcohol compound and the tertiary alcohol ester compound obtained by esterification (i.e., the green fragrance compound) and its use discovered in this invention have not been reported in any prior art. This invention is the first to identify and purify the tertiary alcohol compound, and then obtains the green fragrance compound of this invention for the first time through a subsequent esterification reaction.

[0007] Therefore, the first aspect of the present invention relates to a compound of formula I or an isomer or salt thereof:

[0008] I

[0009] Among them, R1, R2, R3, R4, R5, and R6 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

[0010] 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.

[0011] In a preferred technical solution, three The two non-adjacent bonds in the formula are double bonds, meaning that a compound of formula I or its isomers or salts are compounds of formula I' or their isomers or salts.

[0012] I'

[0013] The definitions of R1, R2, R3, R4, R5, and R6 are the same as in Equation I.

[0014] In another preferred embodiment, the compound of formula I or its isomers or salts are selected from the following compounds or their isomers or salts:

[0015] ;

[0016] More preferably, the following compounds or their isomers or salts:

[0017] .

[0018] The 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 steps of first reacting a compound of formula II or an isomer or salt thereof with a Grignard reagent to generate a compound of formula III, then purifying the compound of formula III or an isomer or salt thereof, and then subjecting the compound of formula III to an esterification reaction:

[0019] II

[0020] III

[0021] Among them, R1, R2, R3, R4, R5 and The definition is the same as in Equation I.

[0022] In a preferred embodiment, the compound of formula II or its isomer or salt is a compound of formula II' or its isomer or salt:

[0023] II'

[0024] The definitions of R1, R2, R3, and R4 are the same as in Equation I.

[0025] In another preferred embodiment, the compound of formula II or its isomers or salts are selected from the following compounds or their isomers or salts:

[0026] ;

[0027] More preferably, the following compounds or their isomers or salts:

[0028] .

[0029] The Grignard reagent may be, for example, R5-MgCl or R5-Li, wherein the definition of R5 is the same as in Formula I.

[0030] The esterification reaction can be carried out using a carboxylic acid or anhydride, such as R6-COOH or (R6-CO)2O, where R6 is defined as in Formula I.

[0031] A third aspect of the present invention relates to a compound of formula III, or an isomer or salt thereof, as a synthetic intermediate for a compound of formula I or an isomer or salt thereof, and its use as a synthetic intermediate for a compound of formula I or an isomer or salt thereof:

[0032] III

[0033] Among them, R1, R2, R3, R4, R5 and The definition is the same as in Equation I.

[0034] In a preferred embodiment, the compound of formula III or its isomer or salt is a compound of formula III' or its isomer or salt:

[0035] III',

[0036] The definitions of R1, R2, R3, R4, and R5 are the same as in Equation I.

[0037] In another preferred embodiment, the compound of formula III or its isomers or salts are selected from the following compounds or their isomers or salts:

[0038] ;

[0039] More preferably, the following compounds or their isomers or salts:

[0040] .

[0041] A fourth aspect of the invention relates to a method for obtaining or increasing an aromatic (specifically, purslane) atmosphere, comprising using a compound of formula I or an isomer or salt thereof. Detailed Implementation

[0042] 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., R / S isomers of the compound of Formula II). The salts described in this specification are, for example, alkoxides or oxonium salts formed from alcohols (including enol configurations resulting from keto-enol tautomerism).

[0043] 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 the Grignard reagent R5-MgCl and the esterification reaction using acid anhydride (R6-CO)2O as an example, the ketone structure in formula II undergoes nucleophilic addition with R5-MgCl to form the tertiary alcohol of formula III, which then forms compound I under the action of (R6-CO)2O.

[0044] Reaction 1

[0045]

[0046] The purification of the compound of formula III can be carried out using any method known in the art, such as chromatography, crystallization, or solid-liquid separation based on melting point differences as used in the examples. The compound of formula III is a byproduct of this reaction step. After the purification of the compound of formula III, the main product of this reaction step, namely the enol salt (or the ketone obtained by tautomerization rearrangement), can still be purified and used as a synthetic starting material for downstream reactions, thus not affecting the overall economic efficiency of the reaction.

[0047] Compounds of Formula I and their isomers or fragrance-acceptable salts can be used in ways known to those skilled in the art to impart and enhance a fresh, grassy aroma and improve the fragrance quality of products. For example, they can be added directly to daily necessities such as shower gels and shampoos, or compounded in fabric care products such as laundry detergents, fabric softeners, and fragrance beads, personal care products such as hand creams, body lotions, and antiperspirants, as well as home fragrance products such as air fresheners and cleaning wipes, to impart a pure, harmonious, and long-lasting fresh natural grassy scent to the products.

[0048] The terms “green aroma,” “green scent type,” “green aroma atmosphere,” and “green grass aroma” used in this article are used interchangeably and have meanings known to those skilled in the art. As mentioned above, it refers to the fresh scent of green grass and / or the aroma of freshly mowed lawn and / or dewy grass in the morning and / or wet grass after rain.

[0049] 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.

[0050] Example

[0051] The starting reactant used in the examples was 1-(2,6,6-trimethylcyclohexyl-1,3-dienyl) ethyl-1-one, which was synthesized and characterized according to the method in patent document CN121107961A.

[0052] Other raw materials used in the examples are commercially available reagents.

[0053] 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 (400MHz), deuterated chloroform (CDCl3) as solvent, tetramethylsilane (TMS) as internal standard, 32 scans, 10ppm spectral width, and chemical shifts recorded using the δ-ppm scale.

[0054] 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), 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.

[0055] The purity of the products obtained from each step of the reaction in the examples was determined by the following gas chromatography (GC) 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.

[0056] 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.

[0057] Example 1: Synthesis of 2-(2,6,6-trimethylcyclohexyl-1,3-dienyl)propyl-2-yl acetate

[0058]

[0059] 2-(2,6,6-trimethylcyclohexyl-1,3-dienyl)propyl-2-yl acetate

[0060] In a 5000 mL four-necked round-bottom flask equipped with a thermometer, mechanical stirrer, reflux condenser, and drying tube (containing anhydrous calcium chloride), 765 mL (2.30 mol) of 3 mol / L methyl magnesium chloride tetrahydrofuran solution was added. The mechanical stirrer was turned on, and the system was cooled to 0 °C. Then, 328 g (2.00 mol) of 1-(2,6,6-trimethylcyclohexyl-1,3-dienyl)ethyl-1-one was slowly added dropwise. During the dropwise addition, the temperature of the reaction system was strictly controlled at 0–5 °C using a cryostat. After the dropwise addition was complete, the reaction was continued at 0–5 °C with stirring for 1 hour.

[0061]

[0062] 1-(2,6,6-trimethylcyclohexyl-1,3-dienyl) 1-ethyl-1-one

[0063] After the reaction was complete, 2500 g (1.28 mol) of a 5% sulfuric acid aqueous solution was slowly added dropwise to the system. After the addition was complete, the mixture was stirred for 30 min, allowed to stand and separate into layers, and the aqueous phase was removed. The organic phase was washed 3-4 times with 500 mL of distilled water until the washings were neutral (pH≈7). The solvent was removed by rotary evaporation under reduced pressure to obtain 330 g of crude product. Gas chromatography (GC) analysis showed that the content of the byproduct (which was identified as 2-(2,6,6-trimethylcyclohexyl-1,3-dienyl)prop-2-ol after purification) in the crude product was approximately 5%.

[0064] The crude product was transferred to a clean flask and placed in a -18°C freezer for 3 hours. Since the main product of this reaction, the enol (or the ketone obtained via tautomerism rearrangement), is liquid at -18°C, while the byproduct 2-(2,6,6-trimethylcyclohexyl-1,3-dienyl)prop-2-ol is solid at -18°C, they can be separated by vacuum filtration and collection of the filter cake. This yielded 14 g of high-purity 2-(2,6,6-trimethylcyclohexyl-1,3-dienyl)prop-2-ol, with a purity of 99.4% as determined by GC. Its structure and mass spectrometry data are shown below.

[0065]

[0066] 2-(2,6,6-trimethylcyclohexyl-1,3-dienyl)prop-2-ol

[0067] Mass spectrometry (m / z): 180 (M+, 0.01), 162 (1), 122 (40), 121 (12), 107 (100), 105 (20), 91 (30), 77 (11), 59 (83), 43 (12).

[0068] In a 100mL four-necked round-bottom flask equipped with a thermometer, mechanical stirrer, reflux condenser, and drying tube (containing anhydrous calcium chloride), 14g of 2-(2,6,6-trimethylcyclohexyl-1,3-dienyl)prop-2-ol obtained according to the aforementioned steps, 0.38g of potassium acetate, and 16g of acetic anhydride were added sequentially. The mechanical stirrer was turned on, and the temperature was slowly raised to 125℃ and reacted at a constant temperature for 2 hours.

[0069] After the reaction was complete, 50 mL of distilled water was slowly added dropwise to the system. After stirring for 30 min, the mixture was allowed to stand and separate into layers. The aqueous phase was then removed. The organic phase was washed 3-4 times with 50 mL of distilled water until the washing solution was neutral (pH≈7). The solvent was removed by rotary evaporation under reduced pressure to obtain 17 g of crude product. GC analysis showed that the product content was 70%.

[0070] The crude product was further separated and purified by silica gel column chromatography: 200-300 mesh silica gel was used as the stationary phase, and petroleum ether-ethyl acetate (95:5 v / v) was used as the eluent. Isocratic elution was employed. During elution, the elution progress was monitored by thin-layer chromatography (TLC, with the same developing solvent as the eluent, and color development under 254 nm UV light). The eluent corresponding to the target component was collected, and the collected eluent was concentrated under reduced pressure to remove the eluent, yielding the product 2-(2,6,6-trimethylcyclohexyl-1,3-dienyl)propyl-2-yl acetate. GC analysis showed that the product purity was 98.5%.

[0071] Product mass spectra (m / z): 222 (M+, 0.02), 164 (12), 162 (24), 147 (30), 121 (90), 119 (17), 107 (11), 105 (32), 101 (32), 91 (30), 79 (12), 77 (14), 59 (43), 43 (100);

[0072] Product NMR: 1H NMR (400 MHz, CDCl3) δ 5.74 – 5.70 (m, 1H), 5.38 (d, J = 9.0 Hz, 1H), 2.83 (s, 3H), 1.88 (d, J = 1.4 Hz, 3H), 1.77 (d, J = 5.2 Hz, 2H), 1.49 (s, 3H), 1.36 (s, 3H), 1.17 (s, 3H), 0.96 (s, 3H).

[0073] Aroma of the product: The aroma is distinctive and pure, with green notes as the main tone. It has a fresh, clear, and crisp texture, much like the scent of tender grass with morning dew and freshly cut green lawn. It has a slight natural green astringency, without any off-flavors or sweetness, and the natural vegetation feeling is prominent. The aroma intensity is moderate and long-lasting, with simple and bright layers. The green aroma base is mellow, while also having a slightly light herbal crispness. It perfectly matches the core characteristics of green aroma fragrances and the fragrance lasts for up to 3 days.

Claims

1. A compound of formula I or an isomer or salt thereof: I in, R1, R2, R3, R4, R5, and R6 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 or an isomer or salt thereof according to claim 1, wherein it is a compound of formula I' or an isomer or salt thereof: I’ The definitions of R1, R2, R3, R4, R5, and R6 are the same as in claim 1; or The compound of formula I, or its isomers or salts, is selected from the following: ； More preferably, the following compounds or their isomers or salts: 。 3. A method for preparing the compound of formula I according to claim 1 or 2, or an isomer or salt thereof, comprising the steps of first reacting the compound of formula II, or an isomer or salt thereof, with a Grignard reagent to generate the compound of formula III, then purifying the compound of formula III, or an isomer or salt thereof, and then subjecting the compound of formula III to an esterification reaction: II III Among them, R1, R2, R3, R4, R5 and The definition is the same as in claim 1.

4. The method according to claim 3, wherein the compound of formula II or its isomer or salt is a compound of formula II' or its isomer or salt: II’ The definitions of R1, R2, R3, and R4 are the same as in claim 1; or The compound of formula II, or its isomers or salts, is selected from the following: ； More preferably, the following compounds or their isomers or salts: ； The Grignard reagent is R5-MgCl or R5-Li, wherein R5 is defined as in claim 1, and The esterification reaction is carried out using R6-COOH or (R6-CO)2O, wherein R6 is defined as in claim 1.

5. Compounds of formula III or their isomers or salts: III, Among them, R1, R2, R3, R4, R5 and The definition is the same as in claim 1.

6. The compound of formula III or an isomer or salt thereof according to claim 5, wherein it is a compound of formula III' or an isomer or salt thereof: III’, The definitions of R1, R2, R3, R4, and R5 are the same as in claim 1; or The compound of formula III or its isomers or salts are selected from the following compounds or their isomers or salts: ； More preferably, the following compounds or their isomers or salts: 。 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 green aroma atmosphere.

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