Fluoroalkyl derivative and preparation method and application thereof

Abstract

The invention discloses a fluoroalkyl derivative ((2E, 4E, 7S)-11-methoxy-3, 7, 11-trimethyl-2, 4-dodecadienoic acid fluoroalkyl ester (or amide)) and a preparation method of the fluoroalkyl derivative ((2E, 4E, 7S)-11-methoxy-3, 7, 11-trimethyl-2, 4-dodecadienoic acid fluoroalkyl ester (or amide)). The compounds comprise structures as shown in a formula (I) and a formula (II). The synthetic method provided by the invention comprises the following step: (2E, 4E, 7S)-11-methoxy-3, 7, 11-trimethyl-2, 4-dodecadienoic acid reacts with fluoroalcohols or fluoroamines with different structures under different esterification or amidation conditions to form corresponding carboxylic acid fluoroalkyl ester (or amide). The compound has a good biological activity inhibition effect on targets such as plutella xylostella and aphis medicaginis, and the compound and the method thereof have wide application prospects. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the technical field of the development of biochemical pesticides, and relates to a class of fluoroalkyl derivatives, their preparation methods and applications, specifically to (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid fluoroalkyl esters (or amides) and their synthesis methods and applications. Background Art

[0002] (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid isopropyl ester (S-methoprene) is one of the most successful biochemical pesticides in the world. It has the advantages of specificity, high efficiency, no (low) toxicity, low resistance, low residue and environmental friendliness. It is considered as a product of "originating from nature, transcending nature and returning to nature". It has played an important role in many non-agricultural fields such as mosquito and fly control, storage pest control, silk production of mulberry silkworms and public health.

[0003] On the other hand, Plutella xylostella belongs to the family Plutellidae of Lepidoptera and is a major world-wide pest that harms cruciferous vegetables. It has been seriously recorded in more than 140 countries and regions around the world and occurs widely in almost all provinces in China. Plutella xylostella has a long damage period and great harmfulness, causing huge economic losses and great troubles to the safe production of cruciferous vegetables. The annual losses caused by Plutella xylostella to the global planting industry reach 4-5 billion US dollars. Due to its own physiological and biochemical characteristics and the continuous use of chemical pesticides, Plutella xylostella has developed varying degrees of resistance to nearly a hundred kinds of insecticides, becoming the most pesticide-resistant agricultural pest in the world, greatly increasing the difficulty of controlling Plutella xylostella. There is an urgent need to develop new green control agents and methods that are highly effective against Plutella xylostella and safe and friendly to the environment and non-target organisms.

[0004] In addition, the alfalfa aphid of the family Aphididae of Hemiptera is a pest that harms a variety of leguminous plants such as alfalfa, peas, broad beans, soybeans and peanuts and is widely distributed worldwide. The alfalfa aphid has a short generation cycle, a large reproduction amount and a fast reproduction speed, and causes serious harm. In addition to direct harm, the alfalfa aphid can also cause indirect harm as a virus transmission vector, which is a serious obstacle to the production of leguminous crops. At present, the large use of chemical pesticides has led to relatively serious resistance, and at the same time poses a potential threat to the ecological environment, bringing great difficulties to field control. There is an urgent need to develop new green agents and methods to control such pests.

[0005] Therefore, it is of great significance to conduct more diverse systematic structural modification and optimization of optically pure S-methoprene and carry out bioactivity tests of the synthesized series of S-methoprene analogs against agricultural pests such as Plutella xylostella and Aphis medicaginis. This not only holds the promise of creating new chiral biochemical pesticides for the safe and green control of the above three types of pests but also provides useful references for the research and development of green pesticides and ecological environmental protection. SUMMARY OF THE INVENTION

[0006] To overcome the problems existing in the prior art, the present invention provides a class of fluoroalkyl derivatives with a new structure, and its structure is shown in formula (1):

[0007]

[0008] In the said formula (1), R F is selected from fluoroalkyl groups containing 1 - 20 carbon atoms, fluoro-substituted aryl groups, and fluoro-substituted heteroaryl groups; wherein, the heteroaryl groups include thiophene, furan, pyridine, pyrrole, pyrazole, pyrimidine, pyrazine, pyridazine, and thiazole; the number of fluorine atoms on the fluoroalkyl carbon chain is 1 - 15; X is O or NH; the chiral configuration of the compound shown in formula (1) is the (S) configuration.

[0009] In a specific embodiment, the present invention provides a class of (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid fluoroalkyl esters, and its structural formula is shown in formula (I):

[0010]

[0011] Wherein, R F is selected from fluoroalkyl groups containing 1 - 20 carbon atoms, fluoro-substituted aryl groups, and fluoro-substituted heteroaryl groups; wherein, the heteroaryl groups include thiophene, furan, pyridine, pyrrole, pyrazole, pyrimidine, pyrazine, pyridazine, and thiazole; the number of fluorine atoms on the fluoroalkyl carbon chain is 1 - 15; the chiral configuration of the compound shown in formula (I) is the (S) configuration.

[0012] In a specific embodiment, the present invention provides a class of (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid fluoroalkyl amides, and its structural formula is shown in formula (II):

[0013]

[0014] Wherein, R FFluoroalkyl groups, fluoro-substituted aryl groups, and fluoro-substituted heteroaryl groups selected from C1-C20; wherein the heteroaryl groups include thiophene, furan, pyridine, pyrrole, pyrazole, pyrimidine, pyrazine, pyridazine, and thiazole; the number of fluorine atoms on the fluoroalkyl carbon chain is 1-15; the chiral configuration of the compound represented by the formula (II) is the (S) configuration.

[0015] Specifically, the fluoroalkyl derivatives provided by the present invention include, but are not limited to, the following compounds:

[0016]

[0017] The present invention also provides a method for preparing the fluoroalkyl derivatives, including a method for preparing (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid fluoroalkyl esters represented by the formula (I) and (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid fluoroalkyl amides represented by the formula (II). Specifically, in a solvent, (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid and a fluoroalcohol or a fluoroamine undergo an esterification or amidation reaction under the action of a condensing agent and a base, and the (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid fluoroalkyl esters represented by the formula (I) or the (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid fluoroalkyl amides represented by the formula (II) can be obtained by separation and purification. The method is shown in the following reaction formula (A):

[0018]

[0019] Wherein, R F is selected from fluoroalkyl groups, fluoro-substituted aryl groups, and fluoro-substituted heteroaryl groups of C1-C20; wherein the heteroaryl groups include thiophene, furan, pyridine, pyrrole, pyrazole, pyrimidine, pyrazine, pyridazine, and thiazole; the number of fluorine atoms on the fluoroalkyl carbon chain is 1-15; X is O or NH; the chiral configurations of both (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid and the compound represented by the formula (1) are the (S) configuration.

[0020] In the method of the present invention, the condensing agent includes, but is not limited to, one or more selected from DIC (N,N-diisopropylcarbodiimide), DCC (N,N-dicyclohexylcarbodiimide), HOBt (hydroxybenzotriazole), HOAt (N-hydroxy-7-azabenzotriazole), HATU (N,N,N',N'-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate), HBTU (benzotriazole-N,N,N',N'-tetramethyluronium hexafluorophosphate), HCTU (6-chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate), or EDC·HCl (1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride), etc. The amount of the condensing agent used is 0.5 to 5 mmol, i.e., 0.5 to 5 equivalents, corresponding to each mmol of (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid. Preferably, the condensing agent is one of HOBt (hydroxybenzotriazole), EDC·HCl (1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride), etc.; the amount of the condensing agent used is 1.5 equivalents.

[0021] In the present invention, the base includes, but is not limited to, one or more selected from triethylamine, diisopropylethylamine, DMAP, pyridine, tributylamine, N,N-dimethylaniline, N-methylpyrrolidine, N-methylpiperidine, etc. The amount of the base used is 0.1 to 4 mmol, i.e., 0.1 to 4 equivalents, corresponding to each mmol of (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid. Preferably, the base is one of triethylamine, diisopropylethylamine, etc.; the amount of the base used is 2.0 equivalents.

[0022] In the present invention, the solvent includes, but is not limited to, one or more selected from toluene, dichloromethane, ethyl acetate, tetrahydrofuran, acetone, acetonitrile, DMF, DMSO, ethanol, methanol, etc.; the amount of the solvent used is 0.1 mL to 50 mL corresponding to each mmol of (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid. Preferably, the solvent is one of dichloromethane, tetrahydrofuran, etc.; the amount of the solvent used is 5 mL per mmol.

[0023] In the present invention, the reaction temperature is -10°C to 100°C. Preferably, the reaction temperature is 0°C or 25°C.

[0024] In the present invention, the reaction time is 0.5 - 100 hours. Preferably, the reaction time is 2 h.

[0025] The present invention also provides fluoroalkyl derivatives synthesized according to the above preparation method, including fluoroalkyl esters of (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid and fluoroalkyl amides of (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid as shown in formula (I) and formula (II).

[0026] The present invention also provides the above-mentioned fluoroalkyl derivatives, including the above two types of compounds of fluoroalkyl esters (amides) of (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid, and their applications in the control of agricultural pests such as Plutella xylostella and Aphis medicaginis, and their applications in the growth inhibition of Plutella xylostella larvae and Aphis medicaginis nymphs.

[0027] The beneficial effects of the present invention include but are not limited to: providing fluoroalkyl derivatives with new structures and their preparation methods, and at the same time providing the applications of the above two types of compounds of fluoroalkyl esters (or amides) of (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid in the control of agricultural pests including but not limited to Plutella xylostella and Aphis medicaginis. The newly synthesized fluoroalkyl derivatives with new structures in the present invention have good activities in the inhibition of specific pests, and preferably have good activities in the growth inhibition of Plutella xylostella larvae and Aphis medicaginis nymphs, and have broad application prospects. Detailed implementation manners

[0028] In combination with the following specific embodiments, the present invention will be further described in detail. The processes, conditions, experimental methods, etc. for implementing the present invention are all common knowledge and well-known common sense in the art except for the specifically mentioned content below, and the present invention has no particularly limited content.

[0029] Example 1:

[0030]

[0031] In a 25 mL Schlenk flask, under nitrogen protection, (2E,4E,7S)-11-methoxy-3,7,11-trimethyldodeca-2,4-dienoic acid (268.4 mg, 1.0 mmol) and DMF (5.0 mL) were added and stirred at room temperature. Then, N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate HATU (570.4 mg, 1.5 mmol) was slowly added and stirred. Subsequently, 2,2-difluoroethanol (123.1 mg, 1.5 mmol) and triethylamine (202.4 mg, 2.0 mmol) were added in sequence and stirred for 4 h. After the raw materials were completely converted, water was added to quench the reaction system, and it was extracted three times with dichloromethane, 10 mL each time; the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 90 / 1 - 10 / 1) to obtain the target product as a colorless oily liquid (297.2 mg, 90% yield, NMR and gas phase purity: 98%). When N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (HATU) was replaced with similar condensation reagents such as benzotriazole-N,N,N',N'-tetramethylurea hexafluorophosphate (HBTU) and 6-chloro-1,1,3,3-tetramethylurea hexafluorophosphate (HCTU), similar yields could also be obtained. [α] D 20 = 3.56 (c = 0.180, CHCl3). 1 H NMR (400 MHz, CDCl3): δ 6.21–6.10 (m, 2H), 6.09–5.82 (m, 1H), 5.74 (s, 1H), 4.30 (td, J = 13.7, 4.1 Hz, 2H), 3.17 (s, 3H), 2.29 (s, 3H), 2.23–2.17 (m, 1H), 2.06 - 1.98 (m, 1H), 1.62 - 1.55 (m, 1H), 1.44–1.28 (m, 6H), 1.14 (s, 6H), 0.89 (d, J = 6.6 Hz, 3H); 13 C NMR (100 MHz, CDCl3): δ 165.9, 155.0, 137.5, 134.5, 115.8, 113.1 (t, J = 241.0 Hz), 74.5, 61.8 (t, J = 29.4 Hz), 49.0, 40.6, 40.1, 37.2, 33.1, 24.9, 21.3, 19.6, 14.1; 1919F NMR (376 MHz, CDCl3): δ -125.37 (s, 2F); IR (neat): 2970, 1721, 1610, 1363, 1235, 1156, 1126, 1080, 963, 893 cm -1 ; HRMS (ESI): Exact mass calcd for C 18 H 30 F2O3Na [M+Na] + : 355.2055, Found: 355.2051.

[0032] Example 2:

[0033]

[0034] In a 25 mL Schlenk flask, (2E,4E,7S)-11-methoxy-3,7,11-trimethyldodeca-2,4-dienoic acid (268.4 mg, 1.0 mmol) and DCM (5.0 mL) were added under nitrogen protection and stirred at room temperature. Then 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) (287.6 mg, 1.5 mmol) was slowly added and stirred. Then DMAP (12.2 mg, 0.1 mmol), 2,2,2-trifluoroethanol (150.1 mg, 1.5 mmol) and triethylamine (151.8 mg, 1.5 mmol) were added in sequence and stirred for 4 h. After the raw materials were completely converted, water was added to quench the reaction system, and it was extracted with dichloromethane three times, 10 mL each time; the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 50 / 1 - 10 / 1) to obtain the target product as a colorless oily liquid (257.0 mg, 73% yield, NMR and gas phase purity: 98%). When 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) was replaced with similar condensation reagents such as N,N-diisopropylcarbodiimide (DIC), 6-chlorobenzotriazol-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU), etc., similar yields could also be obtained. [α] D 20 = 1.36 (c = 0.177, CHCl3). 11H NMR (400 MHz, CDCl3): δ 6.23–6.09 (m, 2H), 5.75 (s, 1H), 4.48 (q, J = 8.5 Hz, 2H), 3.17 (s, 3H), 2.29 (s, 3H), 2.23–2.17 (m, 1H), 2.06 - 1.99 (m, 1H), 1.63 - 1.54 (m, 2H), 1.43–1.41 (m, 2H), 1.37–1.24 (m, 4H), 1.14 (s, 6H), 0.89 (d, J = 6.6 Hz, 3H); 13 13C NMR (100 MHz, CDCl3): δ 165.0, 155.7, 137.8, 134.4, 123.22 (q, J = 277.2 Hz), 115.2, 74.5, 59.6 (q, J = 36.4 Hz), 49.0, 40.6, 40.1, 37.2, 33.1, 24.9, 21.2, 19.5, 14.1; 19 19F NMR (376 MHz, CDCl3): δ -73.72; IR (neat): 2971, 1732, 1610, 1363, 1232, 1135, 1076, 967, 870 cm -1 ; HRMS (ESI): Exact mass calcd for C 18 H 29 F3O3Na [M+Na] + : 373.1961, Found: 373.1946.

[0035] Example 3:

[0036]

[0037] In a 25 mL Schlenk flask, (2E,4E,7S)-11-methoxy-3,7,11-trimethyldodeca-2,4-dienoic acid (268.4 mg, 1.0 mmol) and DMF (5.0 mL) were added under nitrogen protection and stirred at room temperature. Then, benzotriazol-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) (568.9 mg, 1.5 mmol) was slowly added and stirred. Subsequently, 4,4,4-trifluorobutanol (192.1 mg, 1.5 mmol) and triethylamine (303.6 mg, 3.0 mmol) were added successively and stirred for 4 h. After the raw materials were completely converted, water was added to quench the reaction system, and it was extracted three times with dichloromethane, 10 mL each time; the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 50 / 1 - 12 / 1) to obtain the target product as a colorless oily liquid (238.4 mg, 63% yield, NMR and gas phase purity: 99%). When benzotriazol-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) was replaced with similar condensation reagents such as N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (HATU) and N,N-dicyclohexylcarbodiimide (DCC), similar yields could also be obtained. [α] D 20 = 3.32 (c = 0.380, CHCl3). 1 1H NMR (400 MHz, CDCl3): δ 6.17–6.07 (m, 2H), 5.69 (s, 1H), 4.16 (t, J = 6.2 Hz, 2H), 3.17 (s, 3H), 2.27 (s, 3H), 2.23–2.14 (m, 3H), 2.05 - 1.89 (m, 3H), 1.62 - 1.57 (m, 1H), 1.45–1.26 (m, 6H), 1.14 (s, 6H), 0.89 (d, J = 6.6 Hz, 3H); 13 13C NMR (100 MHz, CDCl3): δ 167.0, 153.5, 136.8, 134.7, 127.0 (q, J = 274 Hz), 116.9, 74.6, 61.9, 49.1, 40.6, 40.1, 37.2, 33.2, 30.8 (q, J = 29 Hz), 25.0, 21.7 (q, J = 3 Hz), 21.3, 19.6, 14.0; 19 19F NMR (376 MHz, CDCl3): δ -66.44; IR (neat): 2970, 1715, 1611, 1363, 1237, 1148, 1082, 967, 871 cm -1; HRMS(ESI): Exact mass calcd for C 20 H 33 F3O3Na[M+Na] + : 401.2274, Found: 401.2267.

[0038] Example 4:

[0039]

[0040] In a 25 mL Schlenk flask, (2E,4E,7S)-11-methoxy-3,7,11-trimethyldodeca-2,4-dienoic acid (268.4 mg, 1.0 mmol) and THF (5.0 mL) were added under nitrogen protection and stirred at room temperature. Then, 6-chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU) (496.4 mg, 1.2 mmol) was slowly added and stirred. Subsequently, 2,2,3,3-tetrafluoropropanol (198.1 mg, 1.5 mmol) and triethylamine (253.0 mg, 2.5 mmol) were added in sequence and stirred for 6 h. After complete conversion of the starting materials, the reaction system was quenched with water and extracted three times with 10 mL of dichloromethane each time. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 80 / 1 - 15 / 1) to obtain the target product as a colorless oily liquid (254.2 mg, 66% yield, NMR and gas phase purity: 99%). Similar yields can also be obtained when 6-chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU) is replaced with similar condensation reagents such as N,N'-diisopropylcarbodiimide (DIC) and N,N,N',N'-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (HATU). [α] D 20 = 3.00 (c = 0.350, CHCl3). 1 1H NMR (400 MHz, CDCl3): δ 6.23–6.16 (m, 1H), 6.11 (d, J = 15.6 Hz, 1H), 5.89 (tt, J = 53.2, 4.0 Hz, 1H), 5.73 (s, 1H), 4.49 (t, J = 12.9 Hz, 2H), 3.17 (s, 3H), 2.29 (s, 3H), 2.23–2.17 (m, 1H), 2.06 - 1.99 (m, 1H), 1.63 - 1.60 (m, 1H), 1.53–1.27 (m, 6H), 1.14 (s, 6H), 0.89 (d, J = 6.6 Hz, 3H); 1313C NMR (100 MHz, CDCl3): δ 165.2, 155.7, 137.8, 134.3, 116.8 (t, J = 27.7 Hz), 115.2, 114.3 (tt, J = 248, 28 Hz), 109.2 (tt, J = 249, 36 Hz), 74.5, 59.0 (t, J = 29.2 Hz), 49.0, 40.6, 40.1, 37.2, 33.1, 24.9, 21.3, 19.6, 14.1; 19 19F NMR (376 MHz, CDCl3): δ -123.96, -137.91; IR (neat): 2971, 1731, 1609, 1363, 1240, 1120, 967, 870 cm -1 ; HRMS (ESI): Exact mass calcd for C 19 H 30 F4O3Na [M+Na] + : 405.2023, Found: 405.2025.

[0041] Example 5:

[0042]

[0043] In a 25 mL Schlenk flask, under nitrogen protection, (2E,4E,7S)-11-methoxy-3,7,11-trimethyldodeca-2,4-dienoic acid (268.4 mg, 1.0 mmol) and THF (5.0 mL) were added and stirred at room temperature. Then, N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (HATU) (570.4 mg, 1.5 mmol) was slowly added and stirred. Subsequently, 2,2,3,3,3-pentafluoropropanol (225.1 mg, 1.5 mmol) and diisopropylethylamine (387.7 mg, 3.0 mmol) were added in sequence and stirred for 5 h. After the raw materials were completely converted, water was added to quench the reaction system, and the mixture was extracted with dichloromethane three times, 10 mL each time; the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 80 / 1 - 15 / 1) to obtain the target product as a colorless oily liquid (254.2 mg, 66% yield, NMR and gas phase purity: 99%). When N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate (HATU) was replaced with similar condensation reagents such as N,N-dicyclohexylcarbodiimide (DCC), 6-chlorobenzotriazol-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU), etc., similar yields could be obtained. [α] D 20= 0.74 (c = 0.008, CHCl3). 1 1H NMR (300 MHz, CDCl3): δ 6.26–6.07 (m, 2H), 5.74 (s, 1H), 4.56 (t, J = 17.2 Hz, 2H), 3.17 (s, 3H), 2.29 (s, 3H), 2.25 - 2.16 (m, 1H), 2.07 - 1.98 (m, 1H), 1.60–1.55 (m, 1H), 1.45 - 1.38 (m, 2H), 1.38–1.28 (m, 4H), 1.14 (s, 6H), 0.89 (d, J = 8.8 Hz, 3H); 13 13C NMR (100 MHz, CDCl3): 165.1, 156.0, 138.1, 134.4, 115.1, 74.6, 58.5 (t, J = 27 Hz), 49.1, 40.7, 40.1, 37.2, 33.2, 25.0, 21.3, 19.6, 14.2. 19 19F NMR (376 MHz, CDCl3): δ -83.80 (s), -123.38 (s); IR (neat): 2971, 1732, 1609, 1362, 1200, 1133, 1082, 966, 870 cm -1 ; HRMS (ESI): Exact mass calcd for C 19 H 29 F5O3Na [M+Na] + : 423.1929, Found: 423.1929.

[0044] Example 6:

[0045]

[0046] In a 25 mL Schlenk flask, under nitrogen protection, (2E,4E,7S)-11-methoxy-3,7,11-trimethyldodeca-2,4-dienoic acid (268.4 mg, 1.0 mmol) and CH3CN (5.0 mL) were added and stirred at room temperature. Then, hydroxybenzotriazole (HOBt) (202.7 mg, 1.5 mmol) was slowly added and stirred. Subsequently, hexafluoroisopropanol (252.1 mg, 1.5 mmol), DMAP (183.3 mg, 1.5 mmol), and triethylamine (202.4 mg, 2.0 mmol) were added in sequence and stirred for 8 h. After the raw materials were completely converted, water was added to quench the reaction system, and it was extracted three times with dichloromethane, 10 mL each time. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 40 / 1 - 20 / 1) to obtain the target product as a colorless oily liquid (324.1 mg, 78% yield, NMR and gas phase purity: 98%). When hydroxybenzotriazole (HOBt) was replaced with similar condensation reagents such as N,N'-diisopropylcarbodiimide (DIC), 6-chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU), etc., similar yields could also be obtained. [α] D 20 = 3.50 (c = 0.100, CHCl3). 1 1H NMR (300 MHz, CDCl3): δ 6.33–6.23 (m, 1H), 6.15 (d, J = 15.8 Hz, 1H), 5.85–5.77 (m, 2H), 3.17 (s, 3H), 2.33 (s, 3H), 2.27–2.18 (m, 1H), 2.09 - 2.00 (m, 1H), 1.64 - 1.59 (m, 1H), 1.47–1.26 (m, 6H), 1.14 (s, 6H), 0.90 (d, J = 6.6 Hz, 3H); 13 13C NMR (100 MHz, CDCl3): δ 163.0, 158.7, 139.4, 134.1, 120.7 (q, J = 280 Hz), 113.4, 74.5, 66.4–65.0 (m), 49.0, 40.7, 40.1, 37.2, 33.1, 24.9, 21.3, 19.6, 14.5; 19 19F NMR (376 MHz, CDCl3): δ -73.29; IR (neat): 2969, 1745, 1606, 1363, 1232, 1197, 1107, 952, 883 cm -1 ; HRMS (ESI): Exact mass calcd for C 19 H 28F6O3Na[M+Na] + : 441.1835, Found: 441.1843.

[0047] Example 7:

[0048]

[0049] In a 25 mL Schlenk flask, (2E,4E,7S)-11-methoxy-3,7,11-trimethyldodeca-2,4-dienoic acid (268.4 mg, 1.0 mmol) and DMF (5.0 mL) were added under nitrogen protection and stirred at room temperature. Then N-hydroxy-7-azabenzotriazole (HOAt) (204.2 mg, 1.5 mmol) was slowly added and stirred. Subsequently, 2,2,3,3,4,4,5,5-octafluoropentanol (348.1 mg, 1.5 mmol), DMAP (24.4 mg, 0.2 mmol), and triethylamine (202.4 mg, 2.0 mmol) were added in sequence and stirred for 5 h. After the raw materials were completely converted, water was added to quench the reaction system, and it was extracted three times with dichloromethane, 10 mL each time; the organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 50 / 1 - 10 / 1) to obtain the target product as a colorless oily liquid (249.5 mg, 53% yield, NMR and gas phase purity: 99%). When N-hydroxy-7-azabenzotriazole (HOAt) was replaced with similar condensation reagents such as 1-hydroxybenzotriazole (HOBT) and 6-chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU), similar yields could also be obtained. [α] D 20 = 2.50 (c = 0.525, CHCl3). 1 H NMR (400 MHz, CDCl3): δ 6.24–5.91 (m, 3H), 5.75 (s, 1H), 4.61 (t, J = 14.0 Hz, 2H), 3.17 (s, 3H), 2.30 (s, 3H), 2.24–2.17 (m, 1H), 2.06 - 1.99 (m, 1H), 1.63–1.60 (m, 1H), 1.44–1.27 (m, 6H), 1.14 (s, 6H), 0.89 (d, J = 6.7 Hz, 3H). 1313C NMR (100 MHz, CDCl3): δ 165.1, 155.9, 137.9, 134.4, 117.3 (t, J = 31 Hz), 115.1, 114.8 (t, J = 31 Hz), 113.7–107.3 (m), 105.1 (t, J = 31 Hz), 74.4, 58.6 (t, J = 26.4 Hz), 48.9, 40.6, 40.0, 37.2, 33.1, 24.8, 21.2, 19.5, 14.0; 19 19F NMR (376 MHz, CDCl3): δ -117.57~-119.67 (m, 2F), -125.39 (t, J = 8.2 Hz, 2F), -130.10~-130.17 (m, 2F), -137.22~-137.27 (m, 2F); IR (neat): 2972, 1732, 1609, 1363, 1233, 1170, 1128, 1082, 967, 809 cm -1 ; HRMS (ESI): Exact mass calcd for C 21 H 30 F8O3Na [M+Na] + : 505.1959, Found: 505.1969.

[0050] Example 8:

[0051]

[0052] In a 25 mL Schlenk flask, (2E,4E,7S)-11-methoxy-3,7,11-trimethyldodeca-2,4-dienoic acid (268.4 mg, 1.0 mmol) and DCM (5.0 mL) were added under nitrogen protection and stirred at room temperature. Then, N,N'-dicyclohexylcarbodiimide (DCC) (309.5 mg, 1.5 mmol) was slowly added and stirred. Subsequently, 2,2,3,3,4,4,4-heptafluorobutanol (300.1 mg, 1.5 mmol), DMAP (12.2 mg, 0.1 mmol), and diisopropylethylamine (258.5 mg, 2.0 mmol) were added in sequence and stirred for 7 h. After the raw materials were completely converted, water was added to quench the reaction system, and the mixture was extracted with dichloromethane three times, 10 mL each time. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 50 / 1 - 10 / 1) to obtain the target product as a colorless oily liquid (369.4 mg, 82% yield, NMR and gas phase purity: 99%). Similar yields can also be obtained when N,N'-dicyclohexylcarbodiimide (DCC) is replaced with similar condensation reagents such as benzotriazol-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) and 1-hydroxybenzotriazole (HOBT). [α] D 20 = 2.66 (c = 0.707, CHCl3). 1 1H NMR (400 MHz, CDCl3): δ 6.24–6.10 (m, 2H), 5.75 (s, 1H), 4.60 (t, J = 14.0 Hz, 2H), 3.17 (s, 3H), 2.29 (s, 3H), 2.23–2.17 (m, 1H), 2.06–1.99 (m, 1H), 1.63 - 1.57 (m, 1H), 1.43–1.40 (m, 2H), 1.30–1.25 (m, 4H), 1.14 (s, 6H), 0.89 (d, J = 6.4 Hz, 3H); 13 13C NMR (100 MHz, CDCl3): δ 165.1, 155.9, 138.0, 134.4, 115.1, 74.5, 58.6 (t, J = 26.9 Hz), 49.0, 40.6, 40.1, 37.2, 33.1, 24.9, 21.3, 19.6, 14.1; 19 19F NMR (376 MHz, CDCl3): δ -80.85 (t, J = 9.2 Hz), -120.38~-120.46 (m), -127.63~-127.71 (m); IR (neat): 2937, 1732, 1609, 1354, 1227, 1149, 1085, 967, 870 cm -1; HRMS(ESI): Exact mass calcd for C 20 H 29 F7O3Na [M+Na] + : 473.1897, Found: 473.1910.

[0053] Example 9:

[0054]

[0055] In a 25 mL Schlenk flask, (2E,4E,7S)-11-methoxy-3,7,11-trimethyldodeca-2,4-dienoic acid (268.4 mg, 1.0 mmol) and ethyl acetate (5.0 mL) were added under nitrogen protection and stirred at room temperature. Then, N,N-diisopropylcarbodiimide (DIC) (151.4 mg, 1.2 mmol) was slowly added and stirred. Subsequently, 4,4,4-trifluorobutylamine (190.7 mg, 1.5 mmol), DMAP (61.1 mg, 0.5 mmol), and triethylamine (151.8 mg, 1.5 mmol) were added in sequence and stirred for 4 h. After the raw materials were completely converted, water was added to quench the reaction system, and the mixture was extracted three times with 10 mL of dichloromethane each time. The organic phase was washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 12 / 1 - 5 / 1) to obtain the target product as a colorless oily liquid (237.8 mg, 63% yield, NMR and gas phase purity: 98%). Among them, N,N-diisopropylcarbodiimide (DIC) can be replaced with reagents such as 1-hydroxybenzotriazole (HOBT) and N-hydroxy-7-azabenzotriazole (HOAT) to obtain a similar yield. 1 1H NMR (400 MHz, CDCl3): δ 7.70 (s, 1H), 6.27 (d, J = 8.0 Hz, 1H), 5.84 (s, 1H), 5.76–5.70 (m, 1H), 3.21–3.15 (m, 5H), 2.50–2.41 (m, 2H), 2.06 (s, 3H), 2.00–1.91 (m, 1H), 1.76–1.69 (m, 1H), 1.55–1.51 (m, 2H), 1.45–1.39 (m, 2H), 1.35–1.30 (m, 1H), 1.28–1.11 (m, 9H), 0.95 (d, J = 6.7 Hz, 3H). 1313C NMR (101 MHz, CDCl3): δ 167.2, 149.4, 137.4, 128.8, 126.8, 122.1, 82.3, 49.0, 41.8, 40.0, 39.8, 37.1, 33.3, 29.0, 25.0, 21.1, 21.0, 12.4, 11.8; 19 19F NMR (376 MHz, CDCl3): δ -74.23; IR (neat): IR(neat): 3292, 2970, 1645, 1612, 1539, 1363, 1265, 1193, 1082, 964, 871 cm -1 ; HRMS (ESI): Exact mass calcd for C 20 H 34 F3NO2Na [M+Na] + : 377.4922, Found: 377.2542.

[0056] Example 10

[0057] Growth inhibition experiment on Plutella xylostella larvae: Using chromatographically pure N,N-dimethylformamide as a co-solvent, dilute the compound of the present invention (see Table 1) to 0.04 - 20 mg / L with pure water containing 0.05% Tween-80. The content of N,N-dimethylformamide in the test solution does not exceed 0.1%. Wash the cabbage leaves, dry them, and make leaf discs with a diameter of 5.0 cm. Using the leaf dipping method, immerse the leaves in 100 mL of the test solution, take them out and dry after 10 s, and place them in a 9 cm petri dish. Put 10 healthy late fourth-instar Plutella xylostella larvae of the same size in each petri dish. The whole operation is carried out in a well-ventilated environment. There are 3 replicates for each treatment, and 20 Plutella xylostella larvae for each replicate. The control group is an aqueous solution of Tween-80 containing 0.1% N,N-dimethylformamide. After applying the drug, place the petri dishes in an incubator at 25 ± 1 °C, 50 - 70 RH%, and a light-dark cycle of 14L:10D, and continuously observe the situation of Plutella xylostella turning into adults. The experimental results are shown in Table 1.

[0058] Table 1 Representative data on the growth inhibition of Plutella xylostella larvae by fluoroalkyl ester (amide) compounds in the present invention

[0059]

[0060] Example 11

[0061] Experiment on the inhibition of alfalfa aphid growth: Using chromatographically pure N,N-dimethylformamide as a cosolvent, the compound of the present invention (see Table 2) was diluted to 200, 100, 66.7, 44.4, 29.6, and 14.8 mg / L using pure water containing 0.05% Tween-80, and the N,N-dimethylformamide content in the test solution did not exceed 0.1%. Using the insect-leaf dipping method, the broad bean seedlings with 10 four-day-old alfalfa aphid nymphs were soaked in the test solution for 10 seconds, and the excess liquid was taken out and dried. The insect-infested broad bean seedlings were inserted into a glass bottle containing clean water and cultured at 25±1℃ and a light-dark cycle of 14L:10D. After 5 days, the number of surviving adult aphids and nymphs was recorded. Each treatment was repeated 3 times, with 20 alfalfa aphid nymphs in each repeat, and the control group was a Tween-80 aqueous solution containing 0.1% N,N-dimethylformamide. The results are shown in Table 2.

[0062] Table 2 Representative data of the inhibition of aphid nymphs of alfalfa by fluoroalkyl ester (amide) compounds of the present invention

[0063]

[0064]

[0065] According to the above data, the fluoroalkyl (2E, 4E, 7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoate (amide) provided by the present invention (including the compounds of the present invention listed in Tables 1 and 2 and other compounds of the present invention) have good biological activity and growth inhibitory effects on the larvae of the diamondback moth and the nymphs of the alfalfa aphid.

[0066] The protection content of the present invention is not limited to the above embodiments. Without departing from the spirit and scope of the present invention, changes and advantages that can be thought of by those skilled in the art are included in the present invention and are protected by the attached claims.

Claims

1. A class of fluoroalkyl derivatives, characterized in that, Its structure is shown in formula (1): In the formula (1), R F is selected from C1-C20 fluoroalkyl, fluorine-substituted aryl, fluorine-substituted heteroaryl; wherein, the heteroaryl includes thiophene, furan, pyridine, pyrrole, pyrazole, pyrimidine, pyrazine, pyridazine, thiazole; the number of fluorine atoms on the fluoroalkyl carbon chain is 1-15; X is O, NH; the chiral configuration of the compound shown in the formula (1) is the (S) configuration.

2. The fluoroalkyl derivative according to claim 1, characterized in that, The said formula (1) includes (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid fluoroalkyl esters shown in formula (I) below, and (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid fluoroalkyl amides shown in formula (II) below: Among them, R F is selected from C1-C20 fluoroalkyl, fluorine-substituted aryl, and fluorine-substituted heteroaryl; wherein, the heteroaryl includes thiophene, furan, pyridine, pyrrole, pyrazole, pyrimidine, pyrazine, pyridazine, thiazole; the number of fluorine atoms on the fluoroalkyl carbon chain is 1-15; the chiral configurations of the compounds represented by formula (I) or formula (II) are all (S) configurations.

3. The fluoroalkyl derivative according to claim 1 or 2, characterized in that, It includes the following compounds:

4. The method for preparing a fluoroalkyl derivative according to claim 1, characterized in that, In a solvent, (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid and a fluoroalcohol or fluoroamine undergo an esterification or amidation reaction under the action of a condensing agent and a base, and after separation and purification, a fluoroalkyl derivative shown in formula (1) is obtained; the said preparation method is as shown in reaction formula (A) In the reaction formula (A), R F is selected from C1-C20 fluoroalkyl, fluoro-substituted aryl, and fluoro-substituted heteroaryl; wherein, the heteroaryl includes thiophene, furan, pyridine, pyrrole, pyrazole, pyrimidine, pyrazine, pyridazine, and thiazole; the number of fluorine atoms on the fluoroalkyl carbon chain is 1-15; X is O or NH; the chiral configurations of the (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid and the compound shown in formula (1) are both (S) configurations.

5. The preparation method according to claim 4, characterized in that, The said condensing agent is selected from one or more of N,N-diisopropylcarbodiimide, N,N-dicyclohexylcarbodiimide, hydroxybenzotriazole, N-hydroxy-7-azabenzotriazole, N,N,N',N'-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate, benzotriazole-N,N,N',N'-tetramethylurea hexafluorophosphate, 6-chlorobenzotriazole-1,1,3,3-tetramethylurea hexafluorophosphate or 1-ethyl-(3-dimethylaminopropyl)carbodiimide hydrochloride; the amount of the condensing agent used is 0.5 to 5 mmol corresponding to each mmol of (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid; and / or, The said base is selected from one or more of triethylamine, diisopropylethylamine, DMAP, pyridine, tributylamine, N,N-dimethylaniline, N-methyltetrahydropyrrole, N-methylpiperidine; the amount of the base used is 0.1 to 4 mmol corresponding to each mmol of (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid; and / or, The said solvent is selected from one or more of toluene, dichloromethane, ethyl acetate, tetrahydrofuran, acetone, acetonitrile, DMF, DMSO, ethanol, methanol; the amount of the solvent used is 0.1 mL to 50 mL corresponding to each mmol of (2E,4E,7S)-11-methoxy-3,7,11-trimethyl-2,4-dodecadienoic acid; and / or, The temperature of the said reaction is -10°C to 100°C; and / or, The time of the said reaction is 0.5 - 100 hours.

6. The fluoroalkyl derivative shown in formula (1) prepared by the preparation method according to claim 4, which includes the compounds shown in formula (I) and formula (II).

7. The application of the fluoroalkyl derivative according to any one of claims 1 - 3, 6 and the preparation method according to claim 4 or 5 in the control of agricultural pests such as Plutella xylostella and Aphis medicaginis, and in the growth inhibition of Plutella xylostella larvae and Aphis medicaginis nymphs.

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