Use of nitrone compounds as precursors for producing isoxazolidine mosquito repellent ingredients and / or isoxazolidine cooling ingredients

Abstract

The invention provides application of a nitrone compound as shown in a formula I, a nitrone compound as shown in a formula II and / or a nitrone compound as shown in a formula III as a precursor for generating an isoxazolidine mosquito repelling component and / or an isoxazolidine cooling component. In the formula # imgabs0, R is Me, Et, n-Pr, i-Pr, Cy, t-Bu or Bn. The nitrone compound is used as a precursor of the isoxazolidine mosquito-repelling component and / or the isoxazolidine cooling component for the first time, the isoxazolidine mosquito-repelling component and / or the isoxazolidine cooling component are / is generated by heating to reach the initial ring closing temperature or above, and the repelling rate of the generated isoxazolidine mosquito-repelling component after 24 hours is 100%; the mosquito repelling effect is good, A-level mosquito repelling is achieved, and the generated isoxazolidine mosquito repelling component also has aroma and cooling effects. As a precursor of an isoxazolidine mosquito-repelling component, the nitrone compound can be stored for a long time when mosquito repelling is not needed; when mosquito repelling is needed, release of mosquito repelling components can be controlled by adjusting the heating temperature, and the purposes of slow release and long-acting mosquito repelling are achieved; as a precursor of an isoxazolidine cooling component, the nitrone compound can be stored for a long time when cooling is not needed; when cooling is needed, release of cooling components can be controlled by adjusting the heating temperature, and the purposes of slow release and long-acting cooling are achieved.

Description

Technical Field

[0001] The present invention belongs to the technical field of mosquito repellent small molecules, and specifically relates to the use of nitrone compounds as precursors for generating isoxazolidine mosquito repellent ingredients and / or isoxazolidine cooling ingredients. Background Art

[0002] As consumers have higher and higher requirements for mosquito repellent / cooling products, they hope that mosquito repellent / cooling products can be stored for a long time and have a long-lasting mosquito repellent / cooling effect. In order to meet these needs of consumers, it is urgent to develop some mosquito repellent / cooling ingredient precursors. Mosquito repellent / cooling ingredient precursors themselves do not have mosquito repellent / cooling effects, but they will decompose and release mosquito repellent / cooling ingredient molecules under certain circumstances to achieve mosquito repellent / cooling effects.

[0003] Compared with the direct use of mosquito repellent / cooling ingredients, the mosquito repellent / cooling ingredient precursor can not only meet the needs of long-term storage when mosquito repellent / cooling is not needed, but also provide controlled and sustained release of mosquito repellent / cooling ingredients when mosquito repellent / cooling is needed, thereby achieving the purpose of long-term mosquito repellent / cooling. Summary of the invention

[0004] In order to solve the problems in the prior art, the present invention provides the use of nitrone compounds as precursors for generating isoxazolidine mosquito repellent ingredients and / or isoxazolidine cooling ingredients.

[0005] The specific technical solutions of the present invention are as follows:

[0006] Use of the nitrone compound represented by formula I, the nitrone compound represented by formula II and / or the nitrone compound represented by formula III provided by the present invention as a precursor for generating an isoxazolidine mosquito repellent component and / or an isoxazolidine cooling component: In the formula, R is Me, Et, n-Pr, i-Pr, Cy, t-Bu or Bn. (R is methyl, ethyl, n-propyl, isopropyl, cyclohexyl, tert-butyl or benzyl).

[0007] The above-mentioned use provided by the present invention also has such a technical feature, wherein the method for the nitrone compound shown in formula I, the nitrone compound shown in formula II and / or the nitrone compound shown in formula III to generate an isoxazolidine mosquito repellent component and / or an isoxazolidine cooling component is: heating the nitrone compound shown in formula I, the nitrone compound shown in formula II and / or the nitrone compound shown in formula III.

[0008] The above-mentioned use provided by the present invention also has such a technical feature, wherein the nitrone compound represented by formula I is heated to reach the starting ring-closing temperature or above, and its starting ring-closing temperature is 90-150°C; the nitrone compound represented by formula II is heated to reach the starting ring-closing temperature or above, and its starting ring-closing temperature is 40-105°C; the nitrone compound represented by formula III is heated to reach the starting ring-closing temperature or above, and its starting ring-closing temperature is 40-105°C.

[0009] The present invention also provides a mosquito repellent consumer product, characterized in that the mosquito repellent consumer product comprises at least one of the nitrone compound represented by formula I, the nitrone compound represented by formula II and the nitrone compound represented by formula III in the above-mentioned use.

[0010] The mosquito repellent consumer product provided by the present invention also has such a technical feature that the mosquito repellent consumer product is selected from mosquito repellent spray, mosquito repellent liquid, mosquito repellent aromatherapy, mosquito repellent gel, mosquito repellent bracelet, mosquito repellent patch and electric mosquito coil.

[0011] The present invention also provides a cooling consumer product, characterized in that the cooling consumer product comprises at least one of the nitrone compounds shown in formula I, the nitrone compounds shown in formula II and the nitrone compounds shown in formula III in the above-mentioned use.

[0012] The cooling consumer product provided by the present invention also has such a technical feature that the cooling consumer product is selected from food, beverage, chewing gum, tobacco and tobacco substitute products, dental care products or personal care products.

[0013] Functions and Effects of the Invention

[0014] The present invention uses nitrone compounds as precursors of isoxazolidine mosquito repellent ingredients and / or isoxazolidine cooling ingredients for the first time, and generates isoxazolidine mosquito repellent ingredients and / or isoxazolidine cooling ingredients under heating conditions (heating to reach its initial ring closing temperature or above), and the generated isoxazolidine mosquito repellent ingredients have an avoidance rate of 100% after 24 hours, and have a good mosquito repellent effect, reaching Class A mosquito repellent, and the generated isoxazolidine mosquito repellent ingredients also have both fragrance and cooling effects.

[0015] As a precursor of the isoxazolidine mosquito repellent component, the nitrone compound can satisfy the requirement of long-term storage when no mosquito repellent is needed; and when mosquito repellent is needed, the release of the mosquito repellent component can be controlled by adjusting the heating temperature, thereby achieving the purpose of slow release and long-lasting mosquito repellent. As a precursor of the isoxazolidine cooling component, the nitrone compound can satisfy the requirement of long-term storage when no cooling is needed; and when cooling is needed, the release of the cooling component can be controlled by adjusting the heating temperature, thereby achieving the purpose of slow release and long-lasting cooling. DETAILED DESCRIPTION

[0016] The terms used in the present invention, unless otherwise specified, generally have the meanings that are commonly understood by those of ordinary skill in the art.

[0017] In the following examples, various processes and methods not described in detail are conventional methods well known in the art.

[0018] The reagents used in the following examples were purchased from common commercial sources, and the experimental operations and experimental conditions not specified were referred to the conventional operations and conventional conditions in the art.

[0019] The specific implementation of the present invention is described below with reference to embodiments.

[0020] <Example>

[0021] 1. First, referring to the preparation method of invention patent CN117500783A, 2,6-dimethylhept-5-enal (melon aldehyde), 3,7-dimethyl-oct-6-enal (citronellal) and 2,4,7-trimethyloct-6-enal were used as raw materials to prepare 10 nitrone compounds shown in the following formula:

[0022]

[0023]

[0024] The purity of the 10 nitrone compounds prepared is all ≥90%.

[0025] 2. Heating the nitrone compounds prepared above to make them reach their respective starting ring-closing temperatures or above to form isoxazolidine mosquito repellent components. The ring-closing reaction is as follows:

[0026] 2-1,

[0027] After the ring-closure reaction, the analysis results of the product are: 1 H NMR (400 MHz, CDCl 3 )δ2.91-2.50 (m, 3H), 2.01 (ddd, J=21.1, 15.3, 5.2Hz, 3H), 1.55 (ddd, J=18.9, 17. 9, 9.5Hz, 3H), 1.40 (dd, J=10.7, 7.0Hz, 1H), 1.30-1.05 (m, 5H), 1.04-0.64 (m, 8H)

[0028] GC / MS(EI):m / z(%):197(32)[M] + ,182(100),151(17),126(22),109(18),100(47),60(19)

[0029] The product is 1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole.

[0030] 2-2,

[0031] After the ring-closure reaction, the analysis results of the product are: 1 H NMR (400 MHz, CDCl 3 )δ3.05 (dd, J=13.0, 6.5Hz, 1H), 2.22 (t, J=9.9Hz, 1H), 1.94-1.76 (m, 1H), 1.61-1.35 (m, 4H), 1. 16-1.07(m,6H),0.98-0.90(m,6H),0.83(dt,J=14.1,7.0Hz,6H),0.69(dd,J=24.9,12.7Hz,2H)

[0032] GC / MS(EI):m / z(%):225(18)[M] + ,210(100),168(19),151(7),128(9),109(10),95(19)

[0033] The product is 1-isopropyl-3,3,5,7-tetramethyloctahydrobenzo[c]isoxazole.

[0034] 2-3.

[0035] After the ring-closure reaction, the analysis results of the product are: 1 H NMR (400 MHz, CDCl 3 )δ2.58(s,3H),2.14(td,J=10.9,3.5Hz,1H),1.81-1.55(m,4H),1.49-1.28(m,1H),1.27-1.10(m,4H),1.05(d,J=9.8Hz,3H),0.99-0.81(m,5H)

[0036] GC / MS(EI):m / z(%):183(71)[M] + ,168(54),137(94),126(9),109(15),100(100),95(43),81(44).

[0037] The product is 1,3,3,6-tetramethyloctahydrobenzo[c]isoxazole.

[0038] 2-4,

[0039] After the ring-closure reaction, the analysis results of the product are:1 H NMR (400 MHz, CDCl 3 )δ2.62 (s, 3H), 2.11 (td, J=10.9, 3.1Hz, 1H), 1.78 (dd, J=15.9, 7.2Hz, 3H) , 1.66 (d, J=12.3Hz, 1H), 1.38-1.13 (m, 9H), 1.05 (s, 3H), 0.95-0.73 (m, 5H)

[0040] GC / MS(EI):m / z(%):211(23)[M] + ,210(100),196(33),165(48),153(85),126(61),109(33),96(41),82(66),67(34),55(26)

[0041] The product is 1-isopropyl-3,3,6-trimethyloctahydrobenzo[c]isoxazole.

[0043] 2-5,

[0044] After the ring-closure reaction, the analysis results of the product are: 1 H NMR (400 MHz, CDCl 3 )δ2.78–2.55(m,2H),2.14–2.04(m,1H),1.96–1.89(m,1H),1.88–1.83(m,1H),1.82–1.72(m,4H), 1.71–1.55(m,3H),1.54–1.40(m,1H),1.36–1.15(m,9H),1.08(d,J=6.2Hz,3H),0.99–0.92(m,4H)

[0045] GC / MS(EI):m / z(%):251(36)[M] + ,236(10),208(100),168(15),137(30),81(28),55(29),41(27)

[0046] The product is 1-cyclohexyl-3,3,6-trimethyloctahydrobenzo[c]isoxazole.

[0047] 2-6,

[0048] After the ring-closure reaction, the analysis results of the product are: 1 H NMR (400 MHz, CDCl 3)δ7.38(d,J=7.4Hz,2H),7.29(t,J=7.4Hz,2H),7.26–7.20(m,1H),4.10–3.85(m,2H),2.73–2.27(m,1H),1.91– 1.72(m,2H),1.71–1.59(m,2H),1.48–1.34(m,1H),1.27(d,J=13.9Hz,3H),1.24–1.14(m,1H),1.11–0.81(m,8H)

[0049] GC / MS(EI):m / z(%):259(56)[M] + ,244(31),201(20),176(32),137(45),106(38),91(100),81(26),41(17)

[0050] The product is 3,3,6-trimethyl-1-benzyloctahydrobenzo[c]isoxazole.

[0051] 2-7,

[0052] After the ring-closure reaction, the analysis results of the product are: 1 H NMR (400 MHz, CDCl 3 )δ2.77–2.65(m,2H),2.61(s,3H),2.05–1.88(m,2H),1.72–1.56(m,2H),1.39–1.29(m,1H),1.26(s,6H),0.92(d,J=7.1Hz,3H)

[0053] GC / MS(EI):169(75)[M] + ,154(95),123(100),112(30),96(62),87(70),68(55),42(62)

[0054] The product is 1,3,3,6-tetramethyl-hexahydro-cyclopenta[c]isoxazole.

[0055] 2-8,

[0056] After the ring-closure reaction, the analysis results of the product are: 1 H NMR (400 MHz, CDCl 3)δ3.11–3.01(m,1H),2.96–2.80(m,1H),2.73–2.59(m,1H),2.13–1.91(m,2H),1.75–1.57(m,2H),1.28–1.24(m,3H), 1.24–1.18(m,4H),1.14(d,J=6.2Hz,3H),1.02(d,J=6.2Hz,3H),0.94(d,J=7.0Hz,3H)GC / MS(EI):m / z(%):197(25)[M] + ,182(100),140(37),123(35),81(30),55(13),43(31),41(26)

[0057] The product is 1-isopropyl-3,3,6-trimethyl-hexahydro-cyclopenta[c]isoxazole.

[0058] 2-9,

[0059] After the ring-closure reaction, the analysis results of the product are: 1 H NMR (400 MHz, CDCl 3 )δ3.16–2.99(m,1H),2.72–2.49(m,2H),2.24–2.09(m,1H),2.07–1.90(m,2H), 1.84–1.51(m,7H),1.31–1.23(m,5H),1.23–1.17(m,6H),0.92(d,J=6.9Hz,3H)

[0060] GC / MS(EI):m / z(%):237(40)[M] + ,222(37),194(100),140(55),123(42),55(39),41(25)

[0061] The product is 1-cyclohexyl-3,3,6-trimethyl-hexahydro-cyclopenta[c]isoxazole.

[0062] 2-10,

[0063] After the ring-closure reaction, the analysis results of the product are: 1 H NMR (400 MHz, CDCl 3)δ7.44–7.35(m,2H),7.34–7.27(m,2H),7.26–7.18(m,1H),4.15–3.77(m,2H),2.99(dd,J=8.3,2.4Hz,1H),2.78 –2.64(m,1H),2.09–1.94(m,1H),1.92–1.81(m,1H),1.76–1.60(m,2H),1.33–1.26(m,7H),0.79(d,J=7.1Hz,3H)

[0064] GC / MS(EI):m / z(%):245(40)[M] + ,230(37),186(14),163(16),123(30),91(100),81(20),65(15),41(13)

[0065] The product is 3,3,6-trimethyl-1-benzyl-hexahydro-cyclopenta[c]isoxazole.

[0066] The mosquito repellent effect of the above-mentioned partial ring-closing reaction products was tested.

[0067] The density of the homemade 3 The trimethylsilyl modified aerogel blocks were used as carriers to saturate the adsorption of the cyclization reaction products 1-isopropyl-3,3,5,7-tetramethyloctahydrobenzo[c]isoxazole, 1-isopropyl-3,3,6-trimethyloctahydrobenzo[c]isoxazole, 1,3,3,6-tetramethyloctahydrobenzo[c]isoxazole, 1,3,3,5,7-pentamethyloctahydrobenzo[c]isoxazole, 1,3,3,6-tetramethyl-hexahydro-cyclopenta[c]isoxazole, and 1-isopropyl-3,3,6-trimethyl-hexahydro-cyclopenta[c]isoxazole. The mosquito repellent effect was tested after being placed in a non-sealed environment for 24 hours (tested by Beijing Qingxi Technology Research Institute).

[0068] The preparation steps of trimethylsilyl modified aerogel block are as follows:

[0069] Step S1, mixing tetraethyl orthosilicate, ethanol, water, and ethylene glycol, wherein the mass ratio of tetraethyl orthosilicate, ethanol, water, and ethylene glycol is 1:5:0.2:0.5, and performing a hydrolysis reaction at 60° C. and pH 2.0 for 8 hours to obtain a hydrolysis solution.

[0070] Step S2, adjusting the pH of the hydrolysis solution to 7.6, injecting the solution into a mold to make it gel, and then placing the solution in a 70° C. oven for curing for 12 hours to obtain a gel block after heat curing;

[0071] Step S3, uniformly mix solvent 2 (a mixture of acetone and ethanol, with a mixing mass ratio of 2:1) and modifier hexamethyldisilazane at a mass ratio of 10:1 to obtain a modified solution, immerse the heat-cured gel block obtained in step S2 in the modified solution, place it in an oven at 70°C for curing for 12 hours, and obtain a gel block after heat curing again.

[0072] Step S4, taking out the gel block after heat drying and curing again, and placing it in supercritical CO 2 The extraction reactor was set at 55°C for the extraction stage, 10 MPa for the extraction stage, 45°C for the separation stage, and 5.5 MPa for the separation stage. The extraction was carried out for 6 h, and the density was 0.153 g / cm 3 Trimethylsilyl-modified aerogel blocks.

[0073] The mosquito repellent effect test method is as follows: according to GB / T 30126-2013 test, each test volunteers are two men and two women, take 0.1g of saturated adsorption aerogel block after 24h, spread it on the volunteer's arm (5cm×5cm), each test uses 300 active Aedes albopictus (female adults 4-7d after emergence), the volume of the mosquito cage is 40cm×40cm×40cm, the temperature is 26±1℃, and the relative humidity is 65±10%.

[0074] The test results are: the avoidance rate is 100%, the mosquito repellent effect is very good, reaching Class A mosquito repellent.

[0075] The carrier (self-made with a density of 0.153 g / cm 3 The trimethylsilyl modified aerogel block was placed in a non-sealed environment for 24 hours and then tested for mosquito repellent effect (tested by Beijing Qingxi Technology Research Institute). The test method is the same as above.

[0076] The test result is: no mosquito repellent effect.

[0077] Comparing the above two test results, it can be seen that the isoxazolidine compounds generated by heating the above nitrone compounds to their initial ring-closing temperature or above do have excellent mosquito repellent effects. The above nitrone compounds can be used as precursors of isoxazolidine mosquito repellent ingredients.

[0078] The cooling effect of the above ring-closing reaction product has been confirmed by invention patent CN114761385A. Therefore, the above nitrone compounds can be used as precursors of isoxazolidine cooling ingredients.

[0079] The nitrone compounds with an initial ring-closing temperature of ≤100°C can be ring-closed to generate isoxazolidine mosquito repellent ingredients and / or isoxazolidine cooling ingredients when heated to the initial ring-closing temperature or above in the presence or absence of water. The nitrone compounds with an initial ring-closing temperature of >100°C can only be ring-closed to generate isoxazolidine mosquito repellent ingredients and / or isoxazolidine cooling ingredients when heated to the initial ring-closing temperature or above in the absence of water. When the temperature of the nitrone compounds is lower than the initial ring-closing temperature, they have good stability and can be stored for a long time.

[0080] <Test example>

[0081] 1. The density of the homemade one is 0.153g / cm 3 The trimethylsilyl modified aerogel block was used as a carrier (preparation method is the same as above) to saturate the adsorption of nitrone Then the saturated adsorption aerogel block was placed in a non-sealed 60°C environment (the selection standard of the environmental temperature is: to make the test nitrone molecule reach its initial ring closing temperature or above) for 24 hours and then tested for mosquito repellent effect (tested by Beijing Qingxi Technology Research Institute). The test method is as follows: according to GB / T 30126-2013 test, each test volunteer is two men and two women, 0.1g of saturated adsorption aerogel block placed in a non-sealed 60°C environment for 24 hours was spread out on the volunteer's arm (5cm×5cm), 300 active Aedes albopictus mosquitoes (female adults 4-7 days after emergence) were used in each test, the volume of the mosquito cage was 40cm×40cm×40cm, the temperature was 26±1°C, and the relative humidity was 65±10%.

[0082] The test results are: the avoidance rate is 100%, the mosquito repellent effect is very good, reaching Class A mosquito repellent.

[0083] 2. The carrier (self-made density is 0.153g / cm 3 The mosquito repellent effect of the trimethylsilyl modified aerogel block was tested after being placed in an unsealed 60°C environment for 24 hours (tested by Beijing Qingxi Technology Research Institute). The test method is the same as above.

[0084] The test result is: no mosquito repellent effect.

[0085] 3. The density of the homemade one is 0.153g / cm 3 The trimethylsilyl modified aerogel block was used as a carrier to saturate the adsorption of nitrone The saturated aerogel block was then placed in a non-sealed 30°C environment for 24 hours to test the mosquito repellent effect (tested by Beijing Qingxi Technology Research Institute). The test method is the same as above.

[0086] The test result is: no mosquito repellent effect.

[0087] Comparing the above three test results, it can be seen that heating the nitrone to its initial ring-closing temperature or above can make it close to generate isoxazolidine mosquito repellent ingredients. The nitrone can be used as a precursor of isoxazolidine mosquito repellent ingredients.

[0088] The above is a detailed description of the embodiments, which is convenient for those skilled in the art to correctly understand and use the present invention. Any improvements or modifications to the technical solutions obtained by those skilled in the art based on the present invention on the basis of the prior art, without innovative work, only through analysis, analogy or limited enumeration, etc., should be within the scope of protection determined by the claims.

Claims

1. Use of the nitrone compound represented by formula I, the nitrone compound represented by formula II and / or the nitrone compound represented by formula III as a precursor for producing an isoxazolidine mosquito repellent component and / or an isoxazolidine cooling component: In the formula, R is Me, Et, n-Pr, i-Pr, Cy, t-Bu or Bn.

2. The use according to claim 1, characterized in that in, The method for generating isoxazolidine mosquito repellent component and / or isoxazolidine cooling component from the nitrone compound of formula I, the nitrone compound of formula II and / or the nitrone compound of formula III is: The nitrone compound represented by formula I, the nitrone compound represented by formula II and / or the nitrone compound represented by formula III are heated.

3. The use according to claim 2, characterized in that: in, The nitrone compound represented by formula I is heated to a starting ring-closing temperature or above, wherein the starting ring-closing temperature is 90-150° C.; The nitrone compound represented by formula II is heated to a starting ring-closing temperature or above, wherein the starting ring-closing temperature is 40-105° C.; The nitrone compound represented by formula III is heated to reach the initial ring-closing temperature or above, and the initial ring-closing temperature is 40-105°C.

4. A mosquito repellent consumer product, characterized in that: The mosquito repellent consumer product comprises at least one of the nitrone compound of formula I, the nitrone compound of formula II and the nitrone compound of formula III for the use as described in claim 1.

5. The mosquito repellent consumer product according to claim 4, characterized in that: The mosquito repellent consumer product is selected from mosquito repellent spray, mosquito repellent liquid, mosquito repellent aromatherapy, mosquito repellent gel, mosquito repellent bracelet, mosquito repellent patch and electric mosquito coil.

6. A cooling consumer product, characterized in that: The cooling consumer product comprises at least one of the nitrone compound of formula I, the nitrone compound of formula II and the nitrone compound of formula III in the use as claimed in claim 1.

7. The cooling consumer product according to claim 6, characterized in that The cooling consumer product is selected from food, beverages, chewing gum, tobacco and tobacco substitute products, dental care products or personal care products.

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