A method for synthesizing oxime compounds by catalyzing carbon-hydrogen bond oxidation with tetradentate nitrogen-containing coordinated manganese

Abstract

The invention discloses a method for synthesizing oxime compounds by catalyzing carbon-hydrogen bond oxidation with tetradentate nitrogen-containing coordinated manganese. With tetradentate nitrogen-containing coordinated manganese as a catalyst, under the condition of H2O2 as an oxidant, selective oxidation of carbon-hydrogen bonds of various organic compounds is achieved by adding organic carboxylic acids, and the obtained intermediate product is oximated with hydroxylamine or hydroxylamine hydrochloride or hydroxylamine sulfate, and then further alkalized to generate various ketone oxime structure products such as aromatic ketone oxime, alkyl ketone oxime, allyl ketone oxime, propargyl ketone oxime, etc. with various functional groups. Compared with the existing method, the catalytic reaction raw materials of the present invention are cheap and easy to obtain, the substrate range is wide, the catalyst dosage is small, the reaction conditions are mild, it is green and environmentally friendly, water is the only byproduct in the reaction, the selectivity is good, the yield is high, and the production cost is low.

Description

Technical Field

[0001] The invention belongs to the technical field of selective oxidation of carbon-hydrogen bonds in organic compounds, and specifically relates to a method for synthesizing various ketone oxime structures such as aromatic ketone oxime, allyl ketone oxime, propargyl ketone oxime, chain alkyl ketone oxime, cyclic alkyl ketone oxime, etc., by using a hydrocarbon compound as a catalyst and H2O2 as an oxidant to generate ketones and then oximating the ketones with hydroxylamine or hydroxylamine salt. Background Art

[0002] Oxime is an important class of organic compounds and an important intermediate for the synthesis of many drug molecules, natural products, material molecules, etc. In the synthesis of material molecules, especially in the synthesis of chemical materials, oxime plays an extremely important role as a synthetic intermediate. For example, the synthesis of nylon-6, which is widely used in industry, is obtained by transformation through cyclohexanone oxime, and the synthesis of nylon-12 used for 3D printing materials is obtained by transformation through cyclododecanone oxime. In addition, oxime compounds are also important intermediates for the synthesis of many drug molecules, such as the antiparasitic drug milbemycin oxime, the antidote pralidoxime for the treatment of organophosphorus poisoning, and various antiviral drugs, anticancer drugs, antiparasitic drugs, antidepressant drugs, etc.

[0003] Since oxime compounds have a wide range of uses, chemists have developed a variety of methods for synthesizing oxime compounds. There are five common methods for synthesizing oximes: 1) direct oximation of aldehydes and ketones with hydroxylamine (RSC Advances 2013, 38168-8171); 2) condensation of aldehydes and ketones with ammonium salts or ammonia water and then oxidation to form oximes (Chemical Engineering Science 2016, 152, 717-723); 3) dehydrogenation of alcohols followed by oximation with hydroxylamine (Catalysis Communications 2016, 87, 27-31); 4) oxidative dehydrogenation of amines to form oximes (J Org Chem. 2016, 81, 781-786); 5) free radical reactions of nitroso compounds with carbon-hydrogen bonds to form oximes (ChemPhotoChem. 2018, 2, 22-26). In summary, most of the current methods for synthesizing oximes use functionalized carbon-hydrogen bonds as raw materials. However, the oxidation functionalization of carbon-hydrogen bonds usually requires harsh reaction conditions, the use of equivalent strong oxidants, toxic or expensive metals as catalysts, and a large amount of waste is generated after the reaction. Therefore, the method of synthesizing oximes using functionalized carbon-hydrogen bonds as raw materials is not direct, economical, and environmentally friendly. The oxidation oximation of carbon-hydrogen bonds using nitroso compounds through free radical pathways is a direct process; however, since nitroso compounds are unstable and highly toxic, the requirements for reaction equipment are high and the reaction conditions are also harsh. In recent years, with the strengthening of people's environmental awareness, scientists have begun to explore more green, economical, and simple methods for synthesizing oximes; however, due to the high bond energy of carbon-hydrogen bonds and the small difference in bond energy of different carbon-hydrogen bonds, the yield of synthesizing oxime compounds from simple hydrocarbon compounds is usually low. Therefore, it is necessary to develop efficient and selective catalytic methods to achieve direct oxidative oximation of carbon-hydrogen bonds, so as to provide a method for developing simpler, more efficient, economical and environmentally friendly methods to synthesize more types of oxime compounds. Summary of the invention

[0004] The purpose of the present invention is to provide a method for catalyzing the selective carbon-hydrogen bond oxidation synthesis of aromatic ketoximes, allyl ketoximes, propargyl ketoximes, chain alkyl ketoximes and cyclic alkyl ketoximes with various functional groups by using a low-cost and easily prepared tetradentate nitrogen-containing coordinated manganese as a catalyst.

[0005] In view of the above purpose, the technical scheme adopted by the present invention is: under the conditions of a tetradentate nitrogen-containing coordinated manganese as a catalyst and an organic carboxylic acid as an additive, H2O2 is used as an oxidant to oxidize the carbon-hydrogen bonds of the hydrocarbon compound represented by formula I or I′ or I" or I′" or I′"′ or I′"′ or I′"″ and oximation with hydroxylamine or hydroxylamine hydrochloride or hydroxylamine sulfate, and the oximation product is separated and purified after alkalization to obtain an oxime compound represented by formula II or II′ or II" or II′" or II′"′ or I′"″;

[0006]

[0007]

[0008] In the formula, R represents any one of hydrogen, halogen, methyl, methoxy, ester, acyl, protected amine, and nitro, and R′ represents hydrogen, C1-C 10 Any of the alkyl groups, FG represents C1~C 10 Alkyl, C1~C 10 Alkoxy, phenyl, ester, halogen, acyloxy, amide, cyano, protected amine, C1~C 10 Any of the alkylamine and protected amino acid groups, FG' represents C1~C 10 Alkyl, C1~C 10 Alkoxy, protected amine, C1~C 10 Any one of an alkylamino group and a protected amino acid group; n is an integer of 0 to 15;

[0009] The tetradentate nitrogen-containing coordinated manganese is any one of formula A or B:

[0010]

[0011] In formula A, X represents the coordinated anion Cl - Br - ,I - ,OAc - ,OTf - Any one of the above, where Y in formula B represents the uncoordinated anion ClO4 - 、NO3 - ,BF4 - PF6 - 、SbF6 - Any one of the following, m = 2, or Y represents SO4 2- , m=1; in formula A or formula B Structural representation Any of Structural representation Any one of the R 1 , R 2 , R 3 , R 4 Each independently represents H, C1~C 10 Any of an alkyl group and a silane group.

[0012] The above-mentioned tetradentate nitrogen-containing coordinated manganese is preferably any one of formulas A-1 to A-5:

[0013]

[0014] The organic carboxylic acid is any one of acetic acid, propionic acid, butyric acid, amino acid, etc., and the amount of the organic carboxylic acid added is 1 to 30 times the molar amount of the hydrocarbon.

[0015] The amount of the tetradentate nitrogen-containing coordinated manganese added is 0.01% to 5% of the molar amount of the hydrocarbon.

[0016] The added amount of the above hydroxylamine or hydroxylamine hydrochloride or hydroxylamine sulfate is 0.2 to 5 times the molar amount of the hydrocarbon.

[0017] The amount of H2O2 added is 1 to 15 times the molar amount of the hydrocarbon.

[0018] The reaction conditions of the above method are ice bath reaction for 30 to 300 minutes.

[0019] The solvent used in the above method is any one of tert-butyl alcohol, acetonitrile, acetone, ethyl acetate and trifluoroethanol.

[0020] The alkalization is carried out using sodium bicarbonate, and the alkalization temperature is from room temperature to 80°C.

[0021] The beneficial effects of the present invention are as follows:

[0022] The manganese catalyst of the present invention uses manganese trifluoromethanesulfonate, manganese chloride, manganese bromide, manganese acetate, manganese nitrate, and manganese perchlorate, which are inexpensive and less toxic, as manganese sources, and uses a simple tetradentate nitrogen-containing ligand (for example: 1,1'-bis-(3-methyl-4-methoxypyridine)-2,2'-bipiperidine or 1,1'-bis-(3-triisopropylsilylpyridine)-2,2'-bipiperidine), and is prepared by stirring at 80°C, and the preparation method is simple. The present invention uses hydroxylamine or hydroxylamine salt as an amine source under the action of a synthesized manganese catalyst and H2O2 as an oxidant, and adds organic carboxylic acids to catalyze and selectively oxidize carbon-hydrogen bonds of various organic compounds to synthesize various types of oxime compounds with different functional groups. Compared with the methods that have been reported, the method of the present invention has the advantages of easy availability of raw materials, wide applicability of substrates, low catalyst usage, mild conditions, simple operation, green environmental protection, water is the only byproduct in the reaction, good selectivity, high yield, and low production cost. DETAILED DESCRIPTION

[0023] The present invention is further described in detail below with reference to examples, but the protection scope of the present invention is not limited to these embodiments.

[0024] The synthesis method of the (racemic)-1,1'-bis-(3-methyl-4-methoxypyridine)-2,2'-bipiperidine coordinated manganese catalyst used in the following examples is as follows:

[0025] 1. Synthesis of 1,1'-bis-(3-methyl-4-methoxypyridine)-2,2'-bipiperidin

[0026]

[0027] 336 mg (2.0 mmol, 1 equiv) of bipiperidine and 869 mg (4.2 mmol, 2.1 equiv) of 3-methyl-4-methoxypyridine hydrochloride were weighed in a reaction tube, 20 mL of dichloromethane was added, and then 400 mg (10 mmol, 5 equiv) of sodium hydroxide was dissolved in 4 mL of deionized water and added dropwise to the reaction tube. The reaction was stirred at 55 °C for 5 days. After the reaction was completed, the reaction solution was transferred to a 100 mL separatory funnel, 20 mL of deionized water was added, and the mixture was extracted three times with dichloromethane. The organic phases were combined and the organic phases were dried with anhydrous sodium sulfate. The residue was dried over sodium sulfate to remove water, and then rotary evaporated on a rotary evaporator to obtain a crude product. A mixed solution of petroleum ether / ethyl acetate / triethylamine in a volume ratio of 100:10:0.5 to 100:20:0.5 was used as an eluent. Half of the crude product was purified by silica gel column chromatography to obtain 171 mg (39% yield) of (racemic)-1,1'-bis-(3-methyl-4-methoxypyridine)-2,2'-bipiperidine as a white solid and 127 mg (29% yield) of (meso)-1,1'-bis-(3-methyl-4-methoxypyridine)-2,2'-bipiperidine as a white solid. The other half of the crude product was purified by silica gel column chromatography to obtain a mixture of (racemic, meso)-1,1'-bis-(3-methyl-4-methoxypyridine)-2,2'-bipiperidine as a white solid 311 mg (yield 71% racemic, meso NMR ratio 57:43). The spectral data of (racemic)-1,1'-bis-(3-methyl-4-methoxypyridine)-2,2'-bipiperidine are: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.29 (d, J = 5.6Hz, 2H), 6.62 (d, J = 5.6Hz, 2H), 4.16 (d, J = 12.4Hz, 2H), 3.83 (s, 3H), 3.82 (s, 3H), 3.69 (d, J = 12.0H) z,2H),2.82(s,2H),2.65-2.59(m,2H),2.34-2.30(m,2H),2.19(s,3H) ,2.18(s,3H),1.73-1.50(m,6H),1.24-1.20(m,2H),1.07-0.94(m,4H); 13C NMR (100MHz, CDCl3) δ (ppm): 163.8, 158.2, 147.7, 121.6, 104.3, 64.3, 59.6, 55.4, 54.4, 26.0, 24.9, 24.7, 10.6; HRMS (ESI) m / z C 26 H 38 N4O2[M+H] + Theoretical value 439.3068, measured value 439.3070; (meso)-1,1'-bis-(3-methyl-4-methoxypyridine)-2,2'-bipiperidine spectral data: 1 H NMR(400MHz, CDCl3)δ(ppm):8.26-8.24(m,2H),6.65-6.63(m,2H),4.16(d,J =12.4Hz,2H),3.87-3.78(m,6H),3.76-3.62(d,J=12.4Hz,2H),2.82(s,2H),2 .69-2.56(m,2H),2.32(d,J=12Hz,2H),2.23-2.15(m,6H),1.74-1.65(m,2H) ,1.62-1.49(m,4H),1.25-1.19(m,2H),1.10-1.02(m,2H),1.00-0.87(m,2H); 13 C NMR (100MHz, CDCl3) δ (ppm): 163.9, 159.2, 147.1, 122.1, 104.5, 58.9, 56.1, 55.4, 48.8, 21.4, 21.2, 20.5, 10.5; HRMS (ESI) m / zC 26 H 38 N4O2[M+H] + Theoretical value 439.3068, measured value 439.3070.

[0028] 2. Synthesis of (racemic)-1,1'-bis-(3-methyl-4-methoxypyridine)-2,2'-bipiperidine coordinated manganese catalyst

[0029]

[0030] 89 mg (0.25 mmol, 1 equiv) of manganese trifluoromethanesulfonate (Mn(OTf)2) and 110 mg (0.25 mmol, 1 equiv) (racemic)-1,1'-bis-(3,5-dimethylpyridine)-2,2'-bipiperidine were weighed in a 10 mL reaction tube, and N2 was replaced three times. Then, 3 mL of acetonitrile was added under N2, and the reaction was stirred magnetically at 80 ° C for 8 hours. After the reaction stopped, the reaction solution was cooled to room temperature, and then transferred to a glove box and filtered with diatomaceous earth to remove the solid precipitate, and then transferred to the outside of the glove box and the solvent was drained with an oil pump to obtain a light yellow solid (racemic)-1,1'-bis-(3,5-dimethylpyridine)-2,2'-bipiperidine coordinated manganese catalyst (referred to as (racemic)-A-4) 190 mg, with a yield of 96%. HRMS (ESI) m / z C 28 H 38 F6MnN4O8S2[M-OTf] + :Theoretical value 642.1896, measured value 642.1868.

[0031] The synthesis method of the (racemic)-1,1'-bis-(3-triisopropylsilylpyridine)-2,2'-bipiperidine coordinated manganese catalyst used in the following examples is as follows:

[0032] 1. Synthesis of 1,1'-bis-(3-triisopropylsilylpyridine)-2,2'-bipiperidin

[0033]

[0034] 336 mg (2.0 mmol, 1 equiv) and 1192.4 mg (4.2 mmol, 2.1 equiv) of 3-triisopropylsilylpyridine were weighed in a reaction tube, 20 mL of dichloromethane was added, and then 200 mg (5 mmol, 2.5 equiv) of sodium hydroxide was dissolved in 2 mL of deionized water and added dropwise to the reaction tube. The reaction was stirred at 55 °C for 5 days. After the reaction was completed, the reaction solution was transferred to a 100 mL separatory funnel, 20 mL of deionized water was added, and the mixture was extracted three times with dichloromethane. The organic phases were combined and the organic phases were washed with water. The residue was dried over anhydrous sodium sulfate to remove water, and then rotary evaporated on a rotary evaporator to obtain a crude product. A mixed solution of petroleum ether / ethyl acetate / triethylamine in a volume ratio of 50:3:0.5 to 10:1:0.1 was used as an eluent. Half of the crude product was purified by silica gel column chromatography to obtain 292 mg (44% yield) of (racemic)-1,1'-bis-(3-triisopropylsilylpyridine)-2,2'-bipiperidine as a white solid and 139 mg (21% yield) of (meso)-1,1'-bis-(3-triisopropylsilylpyridine)-2,2'-bipiperidine as a white solid. The other half of the crude product was purified by silica gel column chromatography to obtain a mixture of (racemic, meso)-1,1'-1,1'-bis-(3-triisopropylsilylpyridine)-2,2'-bipiperidine as a white solid 457 mg (yield 69%, racemic to meso NMR ratio 7:3). The spectral data of (racemic)-1,1'-bis-(3-triisopropylsilylpyridine)-2,2'-bipiperidine are: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.59 (s, 2H), 7.71 (dd, J = 7.6, 2.0Hz, 2H), 7.43 (d, J = 8.0Hz, 2H), 4.26 (d, J = 14.4Hz, 2H), 3.20 (d, J = 14.0Hz, 2H), 2.8 6(d,J=11.6Hz,2H),2.70(d,J=10.4Hz,2H),2.06-1.86(m,6H),1.75-1. 70(m,2H),1.59-1.44(m,6H),1.44-1.34(m,6H),1.07(d,J=7.6Hz,36H); 13 C NMR (100MHz, CDCl3) δ (ppm): 160.4, 154.9, 143.4, 127.4, 122.2, 62.7, 60.0, 55.1, 25.8, 24.9, 18.6, 10.8; HRMS (ESI) m / z C 40 H 70 N4Si2[M+H] +Theoretical value: 663.5212, measured value: 663.5205; (meso)-1,1'-bis-(3-triisopropylsilylpyridine)-2,2'-bipiperidine spectral data: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.57 (s, 2H), 7.74 (d, J = 7.6Hz, 2H), 7.50 (d, J = 8.0Hz, 2H), 4.92 (d, J = 14.4Hz, 2H), 3.28 (d, J = 14.8Hz, 2H),2.82(d,J=12.0Hz,2H),2.59(brs,2H),2.00(t,J=10.8Hz,2H),1.77-1.61(m,6H),1.49-1.22(m,12H),1.08(d,J=7.6Hz,36H); 13 C NMR (100MHz, CDCl3) δ (ppm): 161.2, 154.7, 143.6, 127.2, 122.0, 63.5, 60.4, 54.1, 27.3, 24.7, 18.6, 10.8; HRMS (ESI) m / z C 40 H 70 N4Si2[M+H] + Theoretical value: 663.5212, measured value: 663.5205.

[0035] 2. Synthesis of (racemic)-1,1'-bis-(3-triisopropylsilylpyridine)-2,2'-bipiperidine coordinated manganese catalyst

[0036]

[0037] 89 mg (0.25 mmol, 1 equiv) of manganese trifluoromethanesulfonate (Mn(OTf)2) and 166 mg (0.25 mmol, 1 equiv) (racemic)-1,1'-bis-(3-triisopropylsilylpyridine)-2,2'-bipiperidine were weighed in a 10 mL reaction tube, and N2 was replaced three times. Then, 3 mL of acetonitrile was added under N2, and the reaction was stirred magnetically at 80 ° C for 8 hours. After the reaction stopped, the reaction solution was cooled to room temperature, and then transferred to a glove box and filtered with diatomaceous earth to remove the solid precipitate, and then transferred to the outside of the glove box and the solvent was drained with an oil pump to obtain a light yellow solid (racemic)-1,1'-bis-(3-triisopropylsilylpyridine)-2,2'-bipiperidine coordinated manganese catalyst (referred to as (racemic)-A-5) 246 mg, with a yield of 97%. HRMS (ESI) m / z C 42 H 70 F6MnN4O6S2Si[M-OTf] + :Theoretical value 866.4040, measured value 866.4017.

[0038] Example 1

[0039] Synthesize (E)-4-fluoroacetophenone oxime with the following structural formula

[0040]

[0041] 7.92 mg (0.01 mmol) of (racemic)-1,1'-bis-(3-methyl-4-methoxypyridine)-2,2'-bipiperidine manganese catalyst ((racemic)-A-4), 164.10 mg (1.0 mmol) of hydroxylamine sulfate and 64 μL (0.5 mmol) of 4-fluoroethylbenzene were added to a reaction tube, and 3.0 mL of tert-butanol and 0.4 mL (7.0 mmol) of acetic acid were added, and the reaction tube was placed in an ice bath and stirred. Then, 284 μL (2.5 mmol) of a 30% H2O2 aqueous solution was dissolved in 1.0 mL of tert-butanol and added dropwise to the reaction tube via a microinjection pump within 1 hour. After the addition was completed, the reaction was stirred for 20 minutes. After the reaction is completed, anhydrous sodium sulfite solid is added to the reaction solution to quench the remaining H2O2 until the solution does not change color on starch potassium iodide test paper, and anhydrous sodium bicarbonate solid is added at room temperature until the solution pH is about 8, and the reaction product oxime is completely freed by monitoring by TLC. After the alkalization is completed, dichloromethane (10mL×3) and water are extracted, the organic layer is dried with anhydrous sodium sulfate, collected, the solvent is removed by rotary evaporation, and column chromatography is separated to obtain 70 mg of white solid (E)-4-fluoroacetophenone oxime, with a yield of 91%. The spectral data of (E)-4-fluoroacetophenone oxime are: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.42 (brs, 1H, N-OH), 7.61 (dd, J = 8.8, 5.6Hz, 2H, ArH), 7.07 (t, J = 8.8Hz, 2H, ArH), 2.28 (s, 3H); 13 C NMR (100MHz, CDCl3) δ (ppm): 163.6 (d, J C-F =247.0Hz),155.3(C=N),132.7(d,J C-F =4.0Hz),128.0(d,J C-F =8.0Hz),115.6(d,J C-F =21.0Hz),12.5; HRMS(ESI)m / z C8H8FNO[M+Na] + :Theoretical value 176.0482, measured value 176.0488.

[0042] Example 2

[0043] Synthesize (E)-benzoyl oxime with the following structural formula

[0044]

[0045] In Example 1, the 4-fluoroethylbenzene used was replaced by an equal molar amount of octylbenzene, and the other steps were the same as in Example 1 to obtain 88 mg of (E)-octanophenone oxime with a yield of 80%. The spectral data of (E)-octanophenone oxime are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.20 (brs, 1H, N-OH), 7.62-7.60 (m, 2H, ArH), 7.40-7.38 (m, 3H ,ArH),2.82(t,J=7.6Hz,2H),1.60-1.54(m,2H),1.42-1.23(m,8H),0.86(t,J=6.4Hz,3H); 13 C NMR (100MHz, CDCl3) δ (ppm): 160.1 (C = N), 136.0, 129.3, 128.7, 126.5, 31.9, 30.0, 29.2, 26.5, 22.8, 14.2; HRMS (ESI) m / z C 14 H 21 NO[M+Na] + :Theoretical value 242.1515; measured value 242.1513.

[0046] Example 3

[0047] Synthesize (E)-3-acetoxy-1-phenyl-1-acetone oxime with the following structural formula

[0048]

[0049] In Example 1, the 4-fluoroethylbenzene used was replaced by an equal molar amount of 3-phenylpropyl acetate, and the other steps were the same as in Example 1 to obtain 86 mg of (E)-3-acetoxy-1-phenyl-1-acetone oxime with a yield of 83%. The spectral data of (E)-3-acetoxy-1-phenyl-1-acetone oxime are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.46 (brs, 1H, N-OH), 7.65-7.63 (m, 2H, ArH), 7.4 2-7.37(m,3H,ArH),4.36(t,J=7.2Hz,2H),3.18(t,J=7.2Hz,2H),1.97(s,3H); 13C NMR (100MHz, CDCl3) δ (ppm): 171.2 (C=O), 156.2 (C=N), 135.6, 129.6, 128.8, 126.4, 60.9, 26.5, 21.0; HRMS (ESI) m / z C 11 H 13 NO3[M+Na] + :Theoretical value 230.0788, measured value 230.0785.

[0050] Example 4

[0051] Synthesize benzophenone oxime with the following structural formula

[0052]

[0053] In Example 1, the 4-fluoroethylbenzene used was replaced by an equal molar amount of diphenylmethane, and the mixture was alkalized and heated to 80°C. The other steps were the same as in Example 1 to obtain 66 mg of benzophenone oxime with a yield of 67%. The spectral data of benzophenone oxime are as follows: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.33 (brs, 1H, N-OH), 7.50-7.42 (m, 6H), 7.41-7.32 (m, 4H); 13 C NMR (100MHz, CDCl3) δ (ppm): 158.0 (C = N), 136.3, 132.8, 129.7, 129.4, 129.3, 128.5, 128.4, 128.0; HRMS (ESI) m / z C 13 H 11 NO[M+Na] + :Theoretical value 220.0733, measured value 220.0740.

[0054] Example 5

[0055] Synthesize (E)-4-oxime-4-phenylbutyronitrile with the following structural formula

[0056]

[0057] In Example 1, the 4-fluoroethylbenzene used was replaced by an equal molar amount of 4-phenylbutyronitrile, and the other steps were the same as in Example 1 to obtain 78 mg of (E)-4-oximino-4-phenylbutyronitrile with a yield of 89%. The spectral data of (E)-4-oximino-4-phenylbutyronitrile are: 1H NMR (400MHz, CDCl3) δ (ppm): 9.17 (brs, 1H, N-OH), 7.62-7.59 (m, 2H), 7.45-7.40 (m, 3H), 3.17 (t, J = 7.6Hz, 2H), 2.70 (t, J = 7.6Hz, 2H); 13 C NMR (100MHz, CDCl3) δ (ppm): 156.2 (C = N), 134.3, 130.0, 129.0, 126.3, 118.9, 22.9, 14.0; HRMS (ESI) m / z C 13 H 11 NO[M-Na] + Theoretical value is 197.0685, measured value is 197.0688.

[0058] Example 6

[0059] Synthesize (E)-4-oxime-4-phenylbutyric acid methyl ester with the following structural formula

[0060]

[0061] In Example 1, the 4-fluoroethylbenzene used was replaced by an equal molar amount of 4-phenylbutyric acid methyl ester, and the other steps were the same as in Example 1 to obtain 90 mg of (E)-4-oximino-4-phenylbutyric acid methyl ester with a yield of 87%. The spectral data of (E)-4-oximino-4-phenylbutyric acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.33 (brs, 1H, N-OH), 7.63-7.59 (m, 2H, ArH), 7.4 0-7.38(m,3H,ArH),3.66(s,3H),3.14(t,J=8.0Hz,2H),2.64(t,J=8.4Hz,2H); 13 C NMR (100MHz, CDCl3) δ (ppm): 173.2 (C=O), 158.2 (C=N), 135.2, 129.6, 128.8, 126.4, 51.9, 30.6, 22.1; HRMS (ESI) m / z C 11 H 13 NO3[M+Na] + :Theoretical value 230.0788, measured value 230.0785.

[0062] Example 7

[0063] Synthesize methyl (2R,4E)-2-((tert-butyloxycarbonyl)amino)-4-oximino-4-phenylbutyrate of the following structural formula

[0064]

[0065] In Example 1, the 4-fluoroethylbenzene used was replaced by an equal molar amount of (R)-2-((tert-butoxycarbonyl)amino)-4-phenylbutyric acid methyl ester, and the other steps were the same as in Example 1 to obtain 129 mg of (2R,4E)-2-((tert-butoxycarbonyl)amino)-4-oximino-4-phenylbutyric acid methyl ester with a yield of 80%. The spectral data of (2R,4E)-2-((tert-butoxycarbonyl)amino)-4-oximino-4-phenylbutyric acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.71 (brs, 1H, N-OH), 7.63-7.60 (m, 2H), 7.37-7.34 (m, 3H), 5.55 (d, J=7.6Hz,1H),4.62-4.55(m,1H),3.60(s,3H),3.38-3.33(m,1H),3.27-3.22(m,1H),1.37(s,9H); 13 C NMR (100MHz, CDCl3) δ (ppm): 172.5 (C=O), 155.4 (C=N), 135.2, 129.6, 128.7, 126.5, 80.1, 52.5, 51.7, 28.7, 28.4; HRMS (ESI) m / z C 16 H 22 N2O5[M+Na] + Theoretical value is 345.1421, measured value is 345.1423.

[0066] Example 8

[0067] Synthesize (2R,4E)-2-((tert-butyloxycarbonyl)amino)-4-oximino-4-phenylbutane of the following structural formula

[0068]

[0069] In Example 1, the 4-fluoroethylbenzene used was replaced by an equal molar amount of (R)-2-((tert-butoxycarbonyl)amino)-4-phenylbutane, and the other steps were the same as in Example 1 to obtain 117 mg of (2R,4E)-2-((tert-butoxycarbonyl)amino)-4-oximino-4-phenylbutane with a yield of 84%. The spectral data of (2R,4E)-2-((tert-butoxycarbonyl)amino)-4-oximino-4-phenylbutane are: 1H NMR (400MHz, CDCl3) δ (ppm): 9.61 (brs, 1H, N-OH), 7.66-7.62 (m, 2H, ArH), 7.38-7.35 (m, 3H, ArH), 4.87 (brs,1H),4.02-3.95(m,1H),3.20-3.06(m,1H),2.95-2.87(m,1H),1.39(s,9H),1.16(d,J=6.4Hz,3H); 13 C NMR (100MHz, CDCl3) δ (ppm): 157.1 (C = O), 155.4 (C = N), 135.4, 129.4, 128.7, 126.5, 79.2, 45.3, 32.8, 28.5, 21.3; HRMS (ESI) m / z C 15 H 22 N2O3[M+Na] + Theoretical value 301.1523, measured value 301.1521.

[0070] Example 9

[0071] Synthesize the following structural formula of (2S,5E)-2-((tert-butyloxycarbonyl)amino)-5-oximino-5-phenylpentanoic acid methyl ester

[0072]

[0073] In Example 1, the 4-fluoroethylbenzene used was replaced by an equal molar amount of (S)-2-((tert-butoxycarbonyl)amino)-5-phenylpentanoic acid methyl ester, and the other steps were the same as in Example 1 to obtain 136 mg of (S)-2-((tert-butoxycarbonyl)amino)-5-oximino-5-phenylpentanoic acid methyl ester with a yield of 81%. The spectral data of (2S,5E)-2-((tert-butoxycarbonyl)amino)-5-oximino-5-phenylpentanoic acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.91 (brs, 1H, N-OH), 7.59-7.55 (m, 2H, ArH), 7.38-7.35 (m, 3H, ArH), 5.29 (d, J = 8.4Hz, 1 H),4.40(dd,J=8.4,13.2Hz,1H),3.72(s,3H),2.88-2.78(m,2H),2.20-2.03(m,1H),2.00-1.91(m,1H),1.45(s,9H); 13C NMR (100MHz, CDCl3) δ (ppm): 173.1 (C=O), 158.2 (C=O), 155.6 (C=N), 135.3, 129.4, 128.7, 126.2, 80.1, 53.6, 52.4, 28.9, 28.4, 22.4; HRMS (ESI) m / z C 17 H 24 N2O5[M+Na] + Theoretical value is 359.1577, measured value is 359.1576.

[0074] Example 10

[0075] Synthesize (2E,4E) / (2E,4Z)-4-oxime-2-pentenoic acid methyl ester with the following structural formula

[0076]

[0077] 15.84 mg (0.01 mmol) of (racemic)-1,1'-bis-(3-methyl-4-methoxypyridine)-2,2'-bipiperidine manganese catalyst ((racemic)-A-4), 328.0 mg (2.0 mmol) of hydroxylamine sulfate and 158 μL (1.0 mmol) of (E)-2-pentenoic acid methyl ester were added to a reaction tube, and 6.0 mL of tert-butanol and 0.8 mL (14.0 mmol) of acetic acid were added, and the reaction tube was placed in an ice bath and stirred. Then, 568 μL (5.0 mmol) of 30% H2O2 aqueous solution was dissolved in 2.0 mL of tert-butanol and added dropwise to the reaction tube via a microinjection pump within 1 hour. After the addition was completed, the reaction was stirred for 20 minutes. After the reaction is completed, anhydrous sodium sulfite solid is added to the reaction solution to quench the remaining H2O2 until the solution does not change color to starch potassium iodide test paper, and anhydrous sodium bicarbonate solid is added at room temperature until the solution pH is about 8, and the reaction product oxime is completely freed by monitoring by TLC. After the alkalization is completed, dichloromethane (15mL×3) and water are extracted, the organic layer is dried with anhydrous sodium sulfate and collected, the solvent is removed by rotary evaporation, and column chromatography is separated to obtain a light yellow solid (2E, 4E) / (2E, 4Z)-4-oxime-2-pentenoic acid methyl ester mixture ((2E, 4E) / (2E, 4Z)=2:1) 100mg, the yield is 70%. The main isomer (2E, 4E)-4-oxime-2-pentenoic acid methyl ester spectral data are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.96 (brs, 1H), 7.32 (d, J = 16.0Hz, 1H), 6.18 (d, J = 16.0Hz, 1H), 3.76 (s, 3H), 2.01 (s, 3H); 13C NMR (100MHz, CDCl3) δ (ppm): 167.0, 155.3, 141.8, 122.5, 52.1, 9.8; the spectral data of the minor isomer (2E, 4Z)-4-oxime-2-pentenoic acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.96 (brs, 1H), 7.97 (d, J = 16.4Hz, 1H), 6.20 (d, J = 16.4Hz, 1H), 3.78 (s, 3H), 2.03 (s, 3H); 13 C NMR (100MHz, CDCl3) δ (ppm): 167.0, 151.5, 131.3, 125.3, 52.2, 16.7; HRMS (ESI): m / z C6H9NO3 [M+Na] + :Theoretical value 166.0475; measured value 166.0474.

[0078] Embodiment 11

[0079] Synthesize (2E,4E) / (2E,4Z)-4-oximino-2-methyl-2-pentenoic acid methyl ester with the following structural formula

[0080]

[0081] In Example 10, the (E)-2-pentenoic acid methyl ester used was replaced by an equimolar amount of (E)-2-methyl-2-pentenoic acid methyl ester, and the other steps were the same as in Example 10 to obtain 36 mg (yield 23%) of (2E, 4E)-4-oxime-2-methyl-2-pentenoic acid methyl ester and 21 mg (yield 13%) of (2E, 4Z)-4-oxime-2-methyl-2-pentenoic acid methyl ester. The spectral data of (2E, 4E)-4-oxime-2-methyl-2-pentenoic acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.15 (brs, 1H), 7.01 (s.1H), 3.78 (s, 3H), 2.09 (s, 3H), 2.07 (s, 3H); 13 C NMR (100MHz, CDCl3) δ (ppm): 108.6, 154.7, 134.0, 131.9, 52.3, 14.8, 14.7; HRMS (ESI): m / z C7H 11 NO3[M+Na] + : Theoretical value 180.0631; Measured value 180.0628; The spectral data of (2E,4Z)-4-oxime-2-methyl-2-pentenoic acid methyl ester are: 1H NMR (400MHz, CDCl3) δ (ppm): 8.57 (brs, 1H), 7.21 (s.1H), 3.78 (s, 3H), 2.05 (s, 3H), 1.94 (s, 3H); 13 C NMR (100MHz, CDCl3) δ (ppm): 108.0, 152.9, 132.8, 130.4, 52.4, 19.9, 15.3; HRMS (ESI): m / z C7H 11 NO3[M+Na] + :Theoretical value 180.0631; measured value 180.0629.

[0082] Example 12

[0083] Synthesize (2E,4E) / (2E,4Z)-4-oxime-2-hexenoic acid methyl ester with the following structural formula

[0084]

[0085] In Example 10, the (E)-2-pentenoic acid methyl ester used was replaced by an equimolar amount of (E)-2-hexenoic acid methyl ester, and the other steps were the same as in Example 10 to obtain 131 mg of a (2E, 4E) / (2E, 4Z)-4-oxime-2-hexenoic acid methyl ester mixture ((2E, 4E) / (2E, 4Z)=2:1) ​​with a yield of 83%. The spectral data of the main isomer (2E, 4E)-4-oxime-2-hexenoic acid methyl ester are: 1 HNMR (400MHz, CDCl3) δ (ppm): 9.28 (brs, 1H), 7.20 (d, J = 16.4Hz, 1H), 6.15 (d, J = 16.0Hz, 1H), 3.72 (s, 3H), 2.48 (q, J = 7.6Hz, 2H), 1.03 (t, J = 7.6Hz, 3H); 13 C NMR (100MHz, CDCl3) δ (ppm): 167.1, 159.9, 140.9, 122.1, 52.0, 17.7, 10.6; the spectral data of the minor isomer (2E, 4Z)-4-oxime-2-hexenoic acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.28 (brs, 1H), 7.24 (d, J = 16.8Hz, 1H), 6.19 (d, J = 16.0Hz, 1H), 3.73 (s, 3H), 2.39 (q, J = 7.6Hz, 2H), 1.08 (t, J = 7.6Hz, 3H); 13CNMR (100MHz, CDCl3) δ (ppm): 167.1, 159.3, 130.8, 124.8, 52.2, 24.3, 11.5; HRMS (ESI): m / zC7H 11 NO3[M+Na] + :Theoretical value 180.0631; measured value 180.0625.

[0086] Embodiment 13

[0087] Synthesize (2E, 4E) / (2E, 4Z)-4-oxime-2-methyl-2-hexenoic acid methyl ester with the following structural formula

[0088]

[0089] In Example 10, the (E)-2-pentenoic acid methyl ester used was replaced by an equimolar amount of (E)-2-methyl-2-hexenoic acid methyl ester, and the other steps were the same as in Example 10 to obtain 60 mg of a (2E, 4E) / (2E, 4Z)-4-oxime-2-hexenoic acid methyl ester mixture ((2E, 4E) / (2E, 4Z)=2:1) ​​with a yield of 35%. The spectral data of the main isomer (2E, 4E)-4-oxime-2-methyl-2-hexenoic acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.88 (brs, 1H), 6.97 (s, 1H), 3.78 (s, 3H), 2.51 (q, J = 7.6Hz, 2H), 2.07 (s, 3H), 1.11 (t, J = 4.0Hz, 3H); 13 C NMR (100MHz, CDCl3) δ (ppm): 168.6, 132.8, 130.5, 52.4, 21.9, 14.8, 10.3; the spectral data of the minor isomer (2E, 4Z)-4-oxime-2-methyl-2-hexenoic acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.88 (brs, 1H), 7.03 (s, 1H), 3.78 (s, 3H), 2.36 (q, J = 7.6Hz, 2H), 1.88 (s, 3H), 1.09 (t, J = 4.0Hz, 3H); 13 C NMR (100MHz, CDCl3) δ (ppm): 167.8, 133.2, 132.7, 52.3, 27.4, 15.5, 11.1; HRMS (ESI): m / z C8H 13 NO3[M+Na] + :Theoretical value 194.0788; measured value 194.0786.

[0090] Embodiment 14

[0091] Synthesize (2E,4E) / (2E,4Z)-4-oxime-2-heptenoic acid methyl ester with the following structural formula

[0092]

[0093] In Example 10, the (E)-2-pentenoic acid methyl ester used was replaced by an equimolar amount of (E)-2-heptenoic acid methyl ester, and the other steps were the same as in Example 10 to obtain 110 mg of a (2E, 4E) / (2E, 4Z)-4-oxime-2-heptenoic acid methyl ester mixture ((2E, 4E) / (2E, 4Z)=2:1) ​​with a yield of 64%. The spectral data of the main isomer (2E, 4E)-4-oxime-2-heptenoic acid methyl ester are: 1 HNMR (400MHz, CDCl3) δ (ppm): 8.87 (brs, 1H), 7.25 (d, J = 16.4Hz, 1H), 6.18 (d, J = 16.4 Hz,1H),3.76(s,3H),2.49(t,J=7.6Hz,2H),1.60-1.47(m,2H),2.49(t,J=8.0Hz,3H); 13 C NMR (100MHz, CDCl3) δ (ppm): 167.1, 158.7, 141.3, 122.2, 52.0, 26.2, 19.7, 14.3; the spectral data of the minor isomer (2E, 4Z)-4-oxime-2-heptenoic acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.87 (brs, 1H), 7.88 (d, J = 16.4Hz, 1H), 6.23 (d, J = 16.8H z,1H),3.77(s,3H),2.37(t,J=7.6Hz,2H),1.60-1.47(m,2H),2.49(t,J=8.0Hz,3H); 13 C NMR (100MHz, CDCl3) δ (ppm): 167.1, 154.3, 130.9, 124.9, 52.2, 32.8, 20.6, 13.8; HRMS (ESI): m / z C8H 13 NO3[M+Na] + :Theoretical value 194.0788; measured value 194.0787.

[0094] Embodiment 15

[0095] Synthesize (2E,4E) / (2E,4Z)-4-oximino-2-ene-1-octanoic acid methyl ester with the following structural formula

[0096]

[0097] In Example 10, the (E)-2-pentenoic acid methyl ester used was replaced by an equimolar amount of (E)-2-ene-1-octanoic acid methyl ester, and the other steps were the same as in Example 10 to obtain 104 mg of a (2E, 4E) / (2E, 4Z)-4-oxime-2-octenoic acid methyl ester mixture ((2E, 4E) / (2E, 4Z)=2:1), with a yield of 56%. The H NMR spectrum data of the main isomer (2E, 4E)-4-oxime-2-octenoic acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.80 (brs, 1H), 7.26 (d, J = 16.0 Hz, 1H), 6.20 (d, J = 16.4 Hz, 1H), 3.78 (s, 3H), 2.53 (t, J = 7.6 Hz, 2H), 1.56-1.43 (m, 2H), 1.41-1.29 (m, 2H), 0.91 (t, J = 7.2 Hz, 3H); The H NMR spectrum data of the minor isomer (2E, 4Z)-4-oxime-2-octenoic acid methyl ester are as follows: 1 HNMR (400MHz, CDCl3) δ (ppm): 9.80 (brs, 1H), 7.89 (d, J = 16.4Hz, 1H), 6.25 (d, J = 16.8Hz, 1H), 3.79 (s, 3H), 2.41 (t, J = 7.8Hz, 2H), 1.56-1.43 (m, 2H), 1.41-1.29 (m, 2H), 0.90 (t, J = 7.2Hz, 3H); (2E, 4E) / (2E, 4Z)-4-oxime-2-octenoic acid methyl ester NMR mixture carbon spectrum data are: 13 C NMR (100MHz, CDCl3) δ (ppm): 167.0, 159.1, 154.7, 141.3, 130.9, 125.0, 122.3, 7 7.48,52.2,52.1,30.7,29.4,28.4,24.1,23.0,22.5,13.9,13.8; HRMS(ESI):m / z C9H 15 NO3[M+Na] + :Theoretical value 208.0944; measured value 208.0944.

[0098] Example 16

[0099] Synthesize (1E, 3E) / (1E, 3Z)-3-oxime-1-cyclohexenecarboxylic acid methyl ester with the following structural formula

[0100]

[0101] In Example 10, the (E)-2-pentenoic acid methyl ester used was replaced by an equal molar amount of 1-cyclohexenecarboxylic acid methyl ester, and the other steps were the same as in Example 10 to obtain 47 mg (yield 28%) of (1E, 3E)-3-oximino-1-cyclohexenecarboxylic acid methyl ester and 54 mg (yield 32%) of (1E, 3Z)-3-oximino-1-cyclohexenecarboxylic acid methyl ester. The spectral data of (1E, 3E)-3-oximino-1-cyclohexenecarboxylic acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.70 (s, 1H), 7.13 (s, 1H), 3.78 (s, 3H), 2.61 (t, J = 6.6Hz, 2H), 2.43 (t, J = 6.6Hz, 2H), 1.79 (p, J = 6.4Hz, 2H); 13 C NMR (100MHz, CDCl3) δ (ppm): 167.4, 156.5, 136.5, 132.3, 52.2, 24.3, 22.0, 20.6; HRMS (ESI): m / z [M+Na] + 8H 11 NO3[M+Na] + : Theoretical value 192.0631; Measured value 192.0632; The spectral data of (1E,3Z)-3-oxime-1-cyclohexenecarboxylic acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.50 (s, 1H), 7.76 (s, 1H), 3.79 (s, 3H), 2.58-2.35 (m, 4H), 1.86 (p, J = 6.4Hz, 2H); 13 C NMR (100MHz, CDCl3) δ (ppm): 167.7, 153.0, 139.0, 123.0, 52.3, 27.7, 25.5, 22.0; HRMS (ESI): m / z C8H 11 NO3[M+Na] + :Theoretical value 192.0631; measured value 192.0631.

[0102] Embodiment 17

[0103] Synthesize (1E,3E) / (1E,3Z)-3-oxime-1-cyclopentenecarboxylic acid methyl ester with the following structural formula

[0104]

[0105] In Example 10, the (E)-2-pentenoic acid methyl ester used was replaced by an equal molar amount of 1-cyclopentenecarboxylic acid methyl ester, and the other steps were the same as in Example 10 to obtain 84 mg (yield 54%) of (1E, 3E)-3-oximino-1-cyclopentenecarboxylic acid methyl ester and 30 mg (yield 19%) of (1E, 3Z)-3-oximino-1-cyclohexenecarboxylic acid methyl ester. The spectral data of (1E, 3E)-3-oximino-1-cyclopentenecarboxylic acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.51 (s, 1H), 7.00 (s, 1H), 3.79 (s, 3H), 2.92-2.62 (m, 4H); 13 C NMR (100MHz, CDCl3) δ (ppm): 167.4, 165.1, 147.8, 136.5, 52.1, 29.8, 25.3; HRMS (ESI): m / z C7H9NO3 [M+Na] + : Theoretical value 178.0475; Measured value 178.0476; The spectral data of (1E,3Z)-3-oxime-1-cyclohexenecarboxylic acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.85 (s, 1H), 7.42 (s, 1H), 3.81 (s, 3H), 2.74 (m, 4H); 13 C NMR (100MHz, CDCl3) δ (ppm): 165.5, 164.1, 148.8, 129.7, 52.3, 29.0, 27.0; HRMS (ESI): m / z C7H9NO3 [M+Na] + :Theoretical value 178.0475; measured value 178.0475.

[0106] Embodiment 18

[0107] Synthesize the following structural formulas of (2E,4E) / (2E,4Z)-4-oximino-2-ene-1-nonanoic acid methyl ester and (2E,8E) / (2E,8Z)-4-oximino-2-ene-1-nonanoic acid methyl ester

[0108]

[0109] In Example 10, the (E)-2-pentenoic acid methyl ester used was replaced by an equimolar amount of (E)-2-ene-1-nonanoic acid methyl ester, and the other steps were the same as in Example 10, to obtain (2E, 4E) / (2E, 4Z)-4-oximino-2-ene-1-nonanoic acid methyl ester ((2E, 4E) / (2E, 4Z) = 2:1) 112 mg (yield 56%) and (2E, 8E) / (2E, 8Z)-4-oximino-2-ene-1-nonanoic acid methyl ester mixture ((2E, 8E) / (2E, 8Z) = 8:1) 36 mg (yield 18%). The main isomer (2E, 4E)-4-oximino-2-ene-1-nonanoic acid methyl ester H NMR spectrum data are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.43 (brs, 1H), 7.25 (d, J = 16.4Hz, 1H), 6.18 (d, J = 16.4Hz, 1H), 3.77 (s, 3H), 2.51 (t, J = 7.6Hz, 2H), 1.55-1.46 (m, 2H), 1.33-1.28 (m, 4H). The nuclear magnetic resonance hydrogen spectrum data of the minor isomer (2E, 4Z)-4-oximino-2-ene-1-nonanoic acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.43 (br.s, 1H), 7.88 (d, J = 16.8Hz, 1H), 6.24 (d, J = 16.8Hz, 1H), 3.78 (s, 1H), 2.39 (t, J = 7.6Hz, 1H), 1.55-1.46 (m, 2H), 1.33-1.28 (m, 4H). The mixed carbon nuclear magnetic resonance spectrum data of the (2E, 4E) / (2E, 4Z)-4-oximino-2-ene-1-nonanoic acid methyl ester mixture are as follows: 13 C NMR (100MHz, CDCl3) δ (ppm): 167.0, 159.0, 154.7, 141.3, 130.9, 125.0, 122.2, 5 2.2,52.0,32.0,31.5,30.9,27.0,25.9,24.3,22.5,22.4,14.0; HRMS(ESI):m / z C 10 H 17 NO3[M+Na] + : Theoretical value 222.1101; Measured value 22.1097; (2E, 8E) / (2E, 8Z)-4-oxime-2-ene-1-nonanoic acid methyl ester mixed spectrum data are: 1H NMR (400MHz, CDCl3) δ (ppm): 9.05 (brs, 1H), 7.95-7.88 (m, 0.14H), 7.31-7.25 (m, 1H), 6.27-6.21 (m, 0.86H), 3.80 (s, 0.42H), 3.79(s,2.58H),2.60-2.54(m,2H),2.47-2.42(m,1H),2.29-2.25(m,2H),1.90(s,3H),1.81-1.71(m,2H),1.26-1.90(m,1H); 13 C NMR (100MHz, CDCl3) δ (ppm): 167.1, 158.2, 141.2, 122.3, 52.1, 35.6, 23.6, 22.7, 19.9, 13.7; HRMS (ESI): m / z C 10 H 17 NO3[M+Na] + :Theoretical value 222.1101; measured value 22.1099.

[0110] Embodiment 19

[0111] Synthesize (2E, 4E) / (2E, 4Z)-4-oximino-2-ene-1-hexanoic acid (L-valine methyl ester) amide having the following structural formula

[0112]

[0113] In Example 10, the (E)-2-pentenoic acid methyl ester used was replaced by an equimolar amount of (E)-2-ene-1-hexanoic acid (L-valine methyl ester) amide, and the other steps were the same as in Example 10 to obtain 164 mg of a (2E, 4E) / (2E, 4Z)-4-oximino-2-ene-1-hexanoic acid (L-valine methyl ester) amide mixture ((2E, 4E) / (2E, 4Z)=7:2) with a yield of 64%. The spectral data of the main isomer (2E, 4E)-4-oximino-2-ene-1-hexanoic acid (L-valine methyl ester) amide are: 1 H NMR (400MHz, CDCl3) δ (ppm): 10.0 (brs, 1H), 7.21 (d, J = 16.0Hz, 1H), 6.72 (d, J = 8.8Hz, 1H), 6.28 (d, J = 16.0Hz, 1H), 4. 72-4.68(m,1H),3.74(s,3H),2.50(q,J=7.6Hz,2H),2.23-2.14(m,1H),1.06(t,J=7.6Hz,3H),0.92(d,J=5.6Hz,6H); 13C NMR (100MHz, CDCl3) δ (ppm): 173.4, 165.9, 159.6, 137.8, 124.2, 57.4, 52.5, 31.5, 19.1, 18.0, 10.7; the spectral data of the minor isomer (2E, 4Z)-4-oximino-2-ene-1-hexanoic acid (L-valine methyl ester) amide are: 1 H NMR (400MHz, CDCl3) δ (ppm): 10.0 (brs, 1H), 7.72 (d, J = 16.4Hz, 1H), 6.77 (d, J = 8.8Hz, 1H), 6.40 (d, J = 16.0Hz, 1H), 4. 72-4.68(m,1H),3.74(s,3H),2.47(q,J=7.6Hz,2H),2.23-2.14(m,1H),1.11(t,J=7.6Hz,3H),0.91(d,J=5.6Hz,6H); 13 C NMR (100MHz, CDCl3) δ (ppm): 173.2, 165.8, 155.1, 127.9, 127.6, 57.5, 24.8, 18.1, 17.9, 11.7 10.7; HRMS (ESI): m / z C 12 H 20 N2O4[M+Na] + :Theoretical value 279.1315; measured value 279.1311.

[0114] Embodiment 20

[0115] Synthesize (2E, 4E) / (2E, 4Z)-4-oximino-2-ene-1-hexanoic acid (L-tert-leucine methyl ester) amide with the following structural formula

[0116]

[0117] In Example 10, the (E)-2-pentenoic acid methyl ester used was replaced by an equimolar amount of (E)-2-ene-1-hexanoic acid (L-tert-leucine methyl ester) amide, and the other steps were the same as in Example 10 to obtain 146 mg of a (2E, 4E) / (2E, 4Z)-4-oximino-2-ene-1-hexanoic acid (L-tert-leucine methyl ester) amide mixture ((2E, 4E) / (2E, 4Z)=7:2) with a yield of 54%. The spectral data of the main isomer (2E, 4E)-4-oximino-2-ene-1-hexanoic acid (L-tert-leucine methyl ester) amide are: 1H NMR (400MHz, CDCl3) δ (ppm): 10.3 (brs, 1H), 7.18 (d, J = 16.0Hz, 1H), 6.85 (d, J = 9.6Hz, 1H), 6.28 (d,J=15.6Hz,1H),4.60(s,1H),3.67(s,3H),2.47-2.41(m,2H),1.07-0.98(m,3H),0.93(s,9H); 13 C NMR (100MHz, CDCl3) δ (ppm): 172.7, 165.7, 159.3, 137.9, 124.0, 60.2, 52.0, 34.9, 26.6, 17.8, 10.6. The spectral data of the minor isomer (2E, 4Z)-4-oximino-2-ene-1-hexanoic acid (L-tert-leucine methyl ester) amide are: 1 HNMR (400MHz, CDCl3) δ (ppm): 10.3 (brs, 1H), 7.79 (d, J = 16.0Hz, 1H), 6.95 (d, J = 9.6Hz, 1H), 6.40 (d,J=16.0Hz,1H),4.57(s,1H),3.67(s,3H),2.37-2.31(m,2H),1.07-0.98(m,3H),0.93(s,9H); 13 C NMR (100MHz, CDCl3) δ (ppm): 172.5, 165.8, 154.9, 127.9, 127.3, 60.3, 51.9, 34.9, 26.6, 24.6, 11.7; HRMS (ESI): m / zC 13 H 22 N2O4[M+Na] + :Theoretical value 293.1472; measured value 293.1473.

[0118] Embodiment 21

[0119] Synthesize the following structural formula of (E / Z)-4-oximino-2-yne-1-pentanoic acid ethyl ester

[0120]

[0121] In Example 10, the (E)-2-pentenoic acid methyl ester used was replaced by an equimolar amount of 2-alkyne-1-pentanoic acid ethyl ester, and the other steps were the same as in Example 10 to obtain 33 mg of a (E / Z)-4-oxime-2-alkyne-1-pentanoic acid ethyl ester mixture (E / Z) = 1:1) with a yield of 21%. The spectral data of the (E / Z)-4-oxime-2-alkyne-1-pentanoic acid ethyl ester mixture are: 1H NMR (400MHz, CDCl3) δ (ppm): 9.06 (brs, 1H), 4.31-4.24 (m, 2H), 2.10 (s, 1.5H), 2.07 (s, 1.5H), 1.34-1.30 (m, 3H); 13 C NMR (100MHz, CDCl3) δ (ppm): 153.4, 153.2, 141.6, 137.1, 89.3, 81.2, 80.3, 75.7, 62.8, 62.6, 19.6, 15.5, 14.1; HRMS (ESI): m / z C7H9NO3 [M+Na] + :Theoretical value 178.0475; measured value 178.0476.

[0122] Embodiment 22

[0123] Synthesize (Z / E)-2-pentanone oxime with the following structural formula

[0124]

[0125] 10.15 mg (0.01 mmol) of (racemic)-1,1'-bis-(3-triisopropylsilylpyridine)-2,2'-bipiperidine coordinated manganese catalyst ((racemic)-A-5), 82.0 mg (0.5 mmol) of hydroxylamine sulfate and 288 μL (2.5 mmol) of n-pentane were added to a reaction tube, and 3.0 mL of tert-butanol and 0.4 mL (7.0 mmol) of acetic acid were added, and the reaction tube was placed in an ice bath with stirring. Then, 284 μL (2.5 mmol) of a 30% H2O2 aqueous solution was dissolved in 1.0 mL of tert-butanol and added dropwise to the reaction tube via a microinjection pump within 1 hour. After the addition was completed, the reaction was stirred for 20 minutes. After the reaction is completed, anhydrous sodium sulfite solid is added to the reaction solution to quench the remaining H2O2 until the solution does not change color on starch potassium iodide test paper, and anhydrous sodium bicarbonate solid is added at room temperature until the solution pH is about 8, and the reaction product oxime is completely freed by monitoring by TLC. After the alkalization is completed, dichloromethane (10mL×3) and water are extracted, the organic layer is dried with anhydrous sodium sulfate, collected, the solvent is removed by rotary evaporation, and column chromatography is separated to obtain a white solid (Z / E)-2-pentanone oxime mixture (E / Z=3:1) 41mg, the yield is 41%, and the gas chromatography (GC) yield is 69%. The main isomer (E)-2-pentanone oxime spectral data are: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.58 (brs, 1H), 2.17 (t, J = 7.6Hz, 2H), 1.88 (s, 3H), 1.57-1.51 (m, 2H), 0.93 (t, J = 7.6Hz, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm): 158.5 (C=N), 37.8, 19.7, 13.7, 13.5; the spectral data of the minor isomer (Z)-2-pentanone oxime are: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.58 (brs, 1H), 2.36 (t, J = 8.0Hz, 2H), 1.87 (s, 3H), 1.57-1.52 (m, 2H), 0.96 (t, J = 7.6Hz, 3H); 13 C NMR (100MHz, CDCl3) δ (ppm): 158.5 (C = N), 30.7, 19.9, 19.0, 14.3; HRMS (ESI) m / z C5H 11 NO[M+Na] + :Theoretical value 124.0733, measured value 124.0731.

[0126] Embodiment 23

[0127] Synthesize (Z / E)-2-hexanone oxime with the following structural formula

[0128]

[0129] In Example 22, the n-pentane used was replaced by an equimolar amount of n-hexane, and the other steps were the same as in Example 22 to obtain 53 mg of a white solid (Z / E)-2-hexanone oxime mixture (E / Z=3:1), with a yield of 46% and a gas chromatography (GC) yield of 68%. The spectral data of the main isomer (E)-2-hexanone oxime are: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.79 (s, 1H, N-OH), 2.40-2.15 (m, 2H), 1.87 (s, 3H), 1.53-1.43 (m, 2H), 1.39-1.27 (m, 2H), 0.91 (q, J = 7.2Hz, 3H); 13 C NMR (100 MHz, CDCl3) δ (ppm): 159.048 (C=N), 158.69 (C=N), 35.51, 28.50, 28.47, 27.68, 22.89, 22.32, 19.82, 13.90, 13.84, 13.43; the spectral data of the minor isomer (Z)-2-hexanone oxime are: 1H NMR (400MHz, CDCl3) δ (ppm): 8.79 (s, 1H, N-OH), 2.40-2.15 (m, 2H), 1.87 (s, 3H), 1.53-1.43 (m, 2H), 1.39-1.27 (m, 2H), 0.91 (q, J = 7.2Hz, 3H); 13 C NMR (100MHz, CDCl3) δ (ppm): 159.048 (C = N), 158.69 (C = N), 35.51, 28.50, 28.47, 27.68, 22.89, 22.32, 19.82, 13.90, 13.84, 13.43; HRMS (ESI) m / z C6H 13 NO[M+H] + :Theoretical value 116.1070, measured value 116.1071.

[0130] Embodiment 24

[0131] Synthesize (Z / E)-2-heptanone oxime with the following structural formula

[0132]

[0133] In Example 22, the n-pentane used was replaced by an equimolar amount of n-heptane, and the other steps were the same as in Example 22 to obtain 56 mg of a white solid (Z / E)-2-heptanone oxime mixture (E / Z=3:1) with a yield of 43% and a gas chromatography (GC) yield of 55%. The spectral data of the main isomer (E)-2-heptanone oxime are: 1 H NMR (400MHz, CDCl3) δ (ppm): 2.17 (t, J = 7.6Hz, 2H), 1.87 (s, 3H), 1.54-1.46 (m, 2H), 1.35-1.25 (m, 4H), 0.88 (t, J = 7.6Hz, 3H); 13 CNMR (100MHz, CDCl3) δ (ppm): 158.7 (C=N), 35.8, 31.4, 26.0, 22.5, 14.1, 13.5; the spectral data of the minor isomer (Z)-2-heptanone oxime are: 1 H NMR (400MHz, CDCl3) δ (ppm): 2.36 (t, J = 7.6Hz, 2H), 1.86 (s, 3H), 1.54-1.46 (m, 2H), 1.35-1.25 (m, 4H), 0.90 (t, J = 7.6Hz, 3H); 13C NMR (100MHz, CDCl3) δ (ppm): 159.1 (C = N), 32.0, 28.7, 25.3, 22.5, 21.0, 19.9; HRMS (ESI) m / z C7H 15 NO[M+Na] + :Theoretical value 152.1046, measured value 152.1046.

[0134] Embodiment 25

[0135] Synthesize (Z / E)-6-oximino-2-acetoxyheptane with the following structural formula

[0136]

[0137] 10.15 mg (0.01 mmol) of (racemic)-1,1'-bis-(3-triisopropylsilylpyridine)-2,2'-bipiperidine coordinated manganese catalyst ((racemic)-A-5), 328.0 mg (2.0 mmol) of hydroxylamine sulfate and 158 mg (1.0 mmol) of 2-acetoxyheptane were added to a reaction tube, and 6.0 mL of tert-butanol and 0.8 mL (14.0 mmol) of acetic acid were added, and the reaction tube was placed in an ice bath with stirring. Then, 568 μL (5.0 mmol) of 30% H2O2 aqueous solution was dissolved in 1.0 mL of tert-butanol and added dropwise to the reaction tube via a microinjection pump within 1 hour. After the addition was completed, the reaction was stirred for 20 minutes. After the reaction is completed, anhydrous sodium sulfite solid is added to the reaction solution to quench the remaining H2O2 until the solution does not change color on starch potassium iodide test paper, and anhydrous sodium bicarbonate solid is added at room temperature until the solution pH is about 8, and the reaction product oxime is completely freed by monitoring by TLC. After the alkalization is completed, dichloromethane (15mL×3) and water are extracted, the organic layer is dried with anhydrous sodium sulfate, collected, the solvent is removed by rotary evaporation, and column chromatography is separated to obtain a white solid (Z / E)-6-oximino-2-acetoxyheptane mixture (E / Z=2.7:1) 88mg, with a yield of 47%. The main isomer (E)-6-oximino-2-acetoxyheptane hydrogen spectrum data is: 1 H NMR (400 MHz, CDCl3) δ (ppm): 8.33 (brs, 1H), 4.92-4.82 (m, 1H), 2.18 (t, J = 6.8 Hz, 2H), 2.02 (s, 3H), 1.86 (s, 3H), 1.58-1.42 (m, 4H), 1.18 (d, J = 7.2 Hz, 3H); The hydrogen spectrum data of the minor isomer (Z)-6-oximino-2-acetoxyheptane are: 1HNMR (400MHz, CDCl3) δ (ppm): 8.33 (brs, 1H), 4.92-4.82 (m, 1H), 2.37 (t, J = 6.8Hz, 2H), 2.02 (s, 3H), 1.85 (s, 3H), 1.58-1.42 (m, 4H), 1.23 (d, J = 7.2Hz, 3H); (Z / E)-6-oximino-2-acetoxyheptane mixed carbon spectrum data are: 13 C NMR (100MHz, CDCl3) δ (ppm): 170.9 (C=O), 162.1 (C=O), 161.9 (C=N), 158.3 (C=N ),70.9,70.6,35.7,35.5,32.3,31.7,29.8,27.6,23.8,22.2,21.5,21.1,20.1 19.9,13.5,10.8,10.2; HRMS(ESI)m / zC9H 17 NO3[M+Na] + :Theoretical value 210.1101, measured value 210.1107.

[0138] Embodiment 26

[0139] Synthesize (Z / E)-5-oxime-1-hexanoic acid methyl ester with the following structural formula

[0140]

[0141] In Example 25, the 2-acetoxyheptane used was replaced by an equimolar amount of 1-hexanoic acid methyl ester, and the other steps were the same as in Example 25 to obtain 105 mg of a (Z / E)-6-oximino-1-hexanoic acid methyl ester mixture (E / Z=2.5:1) with a yield of 66%. The spectral data of the (Z / E)-6-oximino-1-hexanoic acid methyl ester mixture are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.33 (brs, 1H, N-OH), 3.62 (s, 3H), 2.40-2.12 (m, 4H), 1.92-1.68 (m, 5H); 13 C NMR (100MHz, CDCl3) δ (ppm): 173.7 (C = O), 157.8 (C = N), 157.5 (C = N), 51.6, 35.0, 33.7, 33.2, 27.9, 21.5, 20.8, 19.7, 13.4; HRMS (ESI) m / z C7H 13 NO3[M+Na] + Theoretical value is 182.0788, measured value is 182.0791.

[0142] Embodiment 27

[0143] Synthesize (Z / E)-6-oximino-1-heptanoic acid methyl ester with the following structural formula

[0144]

[0145] In Example 25, the 2-acetoxyheptane used was replaced by an equimolar amount of 1-heptanoic acid methyl ester, and the other steps were the same as in Example 25 to obtain 135 mg of a (Z / E)-6-oximino-1-heptanoic acid methyl ester mixture (E / Z=1.8:1) with a yield of 78%. The spectral data of the main isomer (E)-6-oximino-1-heptanoic acid methyl ester are: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.22 (brs, 1H, N-OH), 3.64 (s, 3H), 2.38-2.24 (m, 4H), 1.84 (s, 3H), 1.69-1.45 (m, 4H); 13 C NMR (100 MHz, CDCl3) δ (ppm): 174.1 (C=O), 158.1 (C=N), 51.6, 35.4, 33.8, 25.0, 24.4, 13.4; the spectral data of the minor isomer (Z)-6-oximino-1-heptanoic acid methyl ester are: 1 HNMR (400MHz, CDCl3) δ (ppm): 9.22 (brs, 1H, N-OH), 3.64 (s, 3H), 2.19-2.13 (m, 4H), 1.84 (s, 3H), 1.69-1.45 (m, 4H); 13 C NMR (100MHz, CDCl3) δ (ppm): 174.2 (C=O), 158.4 (C=N), 35.4, 33.7, 28.2, 25.0, 24.8, 19.8; HRMS (ESI) m / zC8H 15 NO3[M+Na] + Theoretical value is 196.0944, measured value is 196.0946.

[0146] Embodiment 30

[0147] Synthesize (Z / E)-5-oxime-1-acetoxyhexane with the following structural formula

[0148]

[0149] In Example 25, the 2-acetoxyheptane used was replaced by an equimolar amount of 1-acetoxyhexane, and the other steps were the same as in Example 25 to obtain 97 mg of a (Z / E)-5-oxime-1-acetoxyhexane mixture (E / Z=1.6:1) with a yield of 56%. The hydrogen spectrum data of the main isomer (E)-5-oxime-1-acetoxyhexane are:1 H NMR (400 MHz, CDCl3) δ (ppm): 4.13-4.04 (m, 2H), 2.20 (t, J = 7.2 Hz, 2H), 2.03 (s, 3H), 1.87 (s, 3H), 1.68-1.55 (m, 4H); The hydrogen spectrum data of the minor isomer (Z)-5-oximino-1-acetoxyhexane are: 1 H NMR (400MHz, CDCl3) δ (ppm): 4.13-4.04 (m, 2H), 2.39 (t, J = 7.6Hz, 2H), 2.03 (s, 3H), 1.85 (s, 3H), 1.68-1.55 (m, 4H); (Z / E)-5-oxime-1-acetoxyhexane mixed carbon spectrum data are: 13 C NMR (100MHz, CDCl3) δ (ppm): 171.4 (C=O), 158.5 (C=N), 158.2 (C=N), 64.3, 64 .2,35.4,29.8,28.6,28.2,28.1,22.7,22.1,21.1,19.9,13.5; HRMS(ESI)m / z C8H 15 NO3[M+Na] + Theoretical value is 196.0944, measured value is 196.0945.

[0150] Embodiment 29

[0151] The synthetic structure of cyclododecanone oxime is as follows:

[0152]

[0153] 10.15mg (0.01mmol) (racemic)-1,1'-bis-(3-isopropylsilylpyridine)-2,2'-bipiperidine manganese catalyst ((racemic)-A-5), 328mg (2.0mmol) hydroxylamine sulfate and 168mg (1.0mmol) cyclododecane were added to the reaction tube, and 1.0mL tert-butyl alcohol and 1.4mL (24.5mmol) acetic acid were added, and then 568μL (5.0mmol) of 30% H2O2 aqueous solution was dissolved in 2.0mL tert-butyl alcohol and added dropwise to the reaction bottle through a microinjection pump within 1 hour, and the reaction was continued in an ice bath with stirring for 1 hour. After the reaction was completed, anhydrous sodium sulfite solid was added to the reaction solution to quench the remaining H2O2 until the solution did not change color to starch potassium iodide test paper, and anhydrous sodium bicarbonate solid was added at room temperature until the solution pH = 8 or so, and stirred for 1 hour. After alkalization, dichloromethane and water were used for extraction, the organic layer was dried over anhydrous sodium sulfate, collected, the solvent was evaporated, and column chromatography was performed to obtain 180 mg of white solid cyclododecanone oxime, with an isolation yield of 91%. The spectral data of cyclododecanone oxime are as follows:1 HNMR (400MHz, CDCl3) δ (ppm): 8.26 (brs, 1H, N-OH), 2.42 (t, J = 6.4Hz, 2H), 2.26 (t, J = 6.4Hz, 2H), 1.70-1.52 (m, 4H), 1.45-1.27 (m, 14H); 13 C NMR (100MHz, CDCl3) δ (ppm): 160.7 (C = N), 30.4, 26.3, 25.6, 25.2, 24.9, 24.1, 23.6, 23.4, 23.3, 23.2, 22.8; HRMS (ESI) m / zC 12 H 23 NO[M+Na] + :Theoretical value 220.1672, measured value 220.1679.

[0154] In this example, the catalyst used was replaced by (R,R)-A-1 to obtain 61 mg of white solid cyclododecanone oxime with an isolated yield of 31%.

[0155] In this example, the catalyst used was replaced by (R,R)-A-2 to obtain 140 mg of white solid cyclododecanone oxime with an isolated yield of 71%.

[0156] In this example, the catalyst used was replaced by (R,R)-A-3 to obtain 130 mg of white solid cyclododecanone oxime with an isolated yield of 66%.

[0157] In this example, the catalyst used was replaced by (R,R)-A-4 to obtain 177 mg of white solid cyclododecanone oxime with an isolated yield of 90%.

[0158] In this embodiment, 101.5 mg (0.1 mmol) (racemic)-1,1'-bis-(3-isopropylsilylpyridine)-2,2'-bipiperidine manganese catalyst ((racemic)-A-5), 32.8 g (200 mmol) hydroxylamine sulfate and 16.8 g (100 mmol) cyclododecane were added to a 500 mL round-bottom flask, and 100 mL tert-butyl alcohol and 140 mL (2450 mmol) acetic acid were added, and then 56.8 mL (500 mmol) of 30% H2O2 aqueous solution was dissolved in 200 mL tert-butyl alcohol and added dropwise to the reaction bottle within 3 hours through a microinjection pump, and the reaction was continued in an ice bath with stirring for 3 hours. After the reaction was completed, anhydrous sodium sulfite solid was added to the reaction solution to quench the remaining H2O2 until the solution did not change color to starch potassium iodide test paper, and anhydrous sodium bicarbonate solid was added at room temperature until the solution pH = 8 or so, and stirred for 2 hours. After alkalization, the product was extracted with dichloromethane and water, the organic layer was dried over anhydrous sodium sulfate, collected, the solvent was rotary evaporated, and separated by column chromatography to obtain 17.3 g of white solid cyclododecanone oxime with an isolation yield of 88%.

[0159] Embodiment 30

[0160] Synthesize cyclopentanone oxime with the following structural formula

[0161]

[0162] In Example 29, the cyclododecane used was replaced by an equal molar amount of cyclopentane, and the other steps were the same as in Example 29 to obtain 77 mg of cyclopentanone oxime with a yield of 78%. The spectral data of cyclopentanone oxime are: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.43 (brs, 1H, N-OH), 2.46 (t, J = 8.0Hz, 2H), 2.36 (t, J = 6.4Hz, 2H), 1.82-1.67 (m, 4H); 13 CNMR (100MHz, CDCl3) δ (ppm): 167.6 (C=N), 31.0, 27.3, 25.3, 24.7; HRMS (ESI) m / z C5H9NO[M+Na] + :Theoretical value 122.0576, measured value 122.0581.

[0163] Embodiment 31

[0164] The synthetic structure of cyclohexanone oxime is as follows:

[0165]

[0166] In Example 29, the cyclododecane used was replaced by an equal molar amount of cyclohexane, and the other steps were the same as in Example 29 to obtain 96 mg of cyclopentanone oxime with a yield of 85%. The spectral data of cyclohexanone oxime are: 1 H NMR (400MHz, CDCl3) δ (ppm): 7.37 (brs, 1H, N-OH), 2.50 (t, J = 5.6Hz, 2H), 2.21 (t, J = 5.6Hz, 2H), 1.69-1.58 (m, 6H); 13 CNMR (100MHz, CDCl3) δ (ppm): 160.9 (C=N), 32.3, 27.0, 25.9, 25.7, 24.60; HRMS (ESI) m / zC6H 11 NO[M+H] + :Theoretical value 114.0913, measured value 114.0912.

[0167] Embodiment 32

[0168] The synthesis structure of cycloheptanone oxime is as follows:

[0169]

[0170] In Example 29, the cyclododecane used was replaced by an equal molar amount of cycloheptane, and the other steps were the same as in Example 29 to obtain 109 mg of cycloheptanone oxime with a yield of 86%. The spectral data of cycloheptanone oxime are: 1 H NMR (400MHz, CDCl3) δ (ppm): 2.57 (t, J = 6.0 Hz, 2H), 2.37 (t, J = 5.2 Hz, 2H), 1.73-1.48 (m, 8H); 13 C NMR (100MHz, CDCl3) δ (ppm): 164.4 (C = N), 33.8, 30.5, 30.4, 28.6, 27.6, 24.6; HRMS (ESI) m / z C7H 13 NO[M+Na] + :Theoretical value 150.0889, measured value 150.0885.

[0171] Embodiment 33

[0172] The synthetic structure of cyclooctanone oxime is as follows:

[0173]

[0174] In Example 29, the cyclododecane used was replaced by an equal molar amount of cyclooctane, and the other steps were the same as in Example 29 to obtain 126 mg of cyclooctanone oxime with a yield of 89%. The spectrum data of cyclooctanone oxime are: 1H NMR (400MHz, CDCl3) δ (ppm): 7.98 (brs, 1H, N-OH), 2.45 (t, J = 6.4Hz, 2H), 2.29 (t, J = 6.4Hz, 2H), 1.82-1.69 (m, 4H), 1.69-1.58 (m, 6H); 13 C NMR (100MHz, CDCl3) δ (ppm): 164.4 (C = N), 33.4, 27.4, 26.9, 26.7, 25.5, 24.7, 24.6; HRMS (ESI) m / z C8H 15 NO[M+Na] + :Theoretical value 164.1046, measured value 164.1040.

[0175] Embodiment 34

[0176] The synthetic structure is as follows: cyclopentadecanone oxime

[0177]

[0178] In Example 29, the cyclododecane used was replaced by an equal molar amount of cyclopentadecane, and the other steps were the same as in Example 29 to obtain 211 mg of cyclooctanone oxime with a yield of 88%. The spectrum data of cyclopentadecanone oxime are: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.09 (brs, 1H, N-OH), 2.34 (t, J = 7.6Hz, 2H), 2.19 (t, J = 7.6Hz, 2H), 1.64-1.50 (m, 4H), 1.49-1.20 (m, 20H); 13 C NMR (100MHz, CDCl3) δ (ppm): 162.38 (C=N), 34.47, 28.05, 27.57, 27.45, 26.78, 26.65,26.53,26.51,26.49,26.46,26.43,26.42,25.33,24.45; HRMS(ESI)m / z C 15 H 29 NO[M+H] + :Theoretical value 240.2322, measured value 240.2319.

[0179] Embodiment 35

[0180] Synthesize (Z / E)-3-(oxime)cyclopentyl acetate with the following structural formula

[0181]

[0182] In Example 29, the cyclododecane used was replaced by an equal molar amount of cyclopentyl acetate, and the other steps were the same as in Example 29 to obtain 118 mg of a (Z / E)-3-(oxime)cyclopentyl acetate mixture with a yield of 75%. The spectral data of the (Z / E)-3-(oxime)cyclopentyl acetate mixture are: 1 H NMR (400MHz, CDCl3) δ (ppm): 8.07 (brs, 1H, N-OH), 5.30-5.24 (m, 1H), 2.81-2.42 (m, 4H), 2.03 (s, 3H), 2.02-1.93 (m, 2H); 13 C NMR (100MHz, CDCl3) δ (ppm): 170.8 (C = O), 164.0 (C = N), 163.7 (C = N), 74.0, 37.2, 34.2, 31.0, 30.5, 28.0, 24.8, 21.3; HRMS (ESI) m / z C7H 11 NO3[M+Na] + :Theoretical value 180.0631, measured value 80.0639.

[0183] Embodiment 36

[0184] Synthesis of (Z / E)-1-((tert-butyloxycarbonyl)amino)-3-oximinocyclopentylcarboxylic acid methyl ester having the following structural formula

[0185]

[0186] In Example 29, the cyclododecane used was replaced by an equal molar amount of 1-((tert-butoxycarbonyl)amino)-cyclopentylcarboxylic acid methyl ester, and the other steps were the same as in Example 29 to obtain 191 mg of a mixture of (Z / E)-1-((tert-butoxycarbonyl)amino)-3-oximinocyclopentylcarboxylic acid methyl esters with a yield of 70%. The spectral data of the mixture of (Z / E)-1-((tert-butoxycarbonyl)amino)-3-oximinocyclopentylcarboxylic acid methyl esters are as follows: 1 H NMR(400MHz, CDCl3)δ(ppm):8.86(brs,1H,N-OH),5.22(brs,1H),3.73(s,3H),3.13-2.77(m,2H),2.71-2.44(m,2H),2.35-2.08(m,2H),1.41(s,9H); 13C NMR (100MHz, CDCl3) δ (ppm): 173.8 (C = O), 173.5 (C = O), 162.9 (C = N), 162.60 (C = N) 155.5 (C = O) ,155.4(C=O),80.5,64.2,52.8,41.0,34.0,29.8,28.4,28.3,28.2,25.1,24.6; HRMS(ESI)m / z C 12 H 20 N2O5[M+Na] + Theoretical value 295.1264, measured value 295.1265.

[0187] Embodiment 37

[0188] Synthesis of 2-((Z / E)-3-oximino)cyclopentyl-2-((tert-butyloxycarbonyl)aminoacetic acid methyl ester having the following structural formula:

[0189]

[0190] In Example 29, the cyclododecane used was replaced by an equal molar amount of 2-cyclopentyl-2-((tert-butoxycarbonyl)aminoacetic acid methyl ester, and the other steps were the same as in Example 29 to obtain 180 mg of a 2-((Z / E)-3-oximino)cyclopentyl-2-((tert-butoxycarbonyl)aminoacetic acid methyl ester mixture with a yield of 63%. The spectral data of the 2-((Z / E)-3-oximino)cyclopentyl-2-((tert-butoxycarbonyl)aminoacetic acid methyl ester mixture are: 1 H NMR(400MHz, CDCl3)δ(ppm):8.99(brs,1H,N-OH),5.32-5.21(m,1H),4.35(brs,1H),3.72(s, 3H),2.74-2.56(m,1H),2.52-2.11(m,4H),1.96-1.77(m,1H),1.60-1.46(m,1H),1.41(s,9H); 13 C NMR (100MHz, CDCl3) δ (ppm): 172.7 (C=O), 164.7 (C=N), 164.5 (C=N), 155.60 (C=O), 80.3, 55.8, 55.6 ,52.5,47.8,41.3,33.8,33.0,30.2,30.0,29.8,28.4,27.9,27.3,27.2,26.8,26.5; HRMS(ESI)m / z C 13 H 22 N2O5[M+Na] + Theoretical value is 309.1421, measured value is 309.1416.

[0191] Embodiment 38

[0192] Synthesize methyl ((Z / E)-3-oximinocyclopentyl)formate of the following structural formula

[0193]

[0194] In Example 29, the cyclododecane used was replaced by an equal molar amount of cyclopentyl methyl carboxylate, and the other steps were the same as in Example 29 to obtain 127 mg of a ((Z / E)-3-oximinocyclopentyl)methyl formate mixture with a yield of 81%. The spectral data of the ((Z / E)-3-oximinocyclopentyl)methyl formate mixture were: 1 H NMR (400MHz, CDCl3) δ (ppm): 9.58 (brs, 1H, N-OH), 3.63 (s, 3H), 2.96-2.26 (m, 5H), 2.13-1.96 (m, 1H), 1.96-1.80 (m, 1H); 13 C NMR (100MHz, CDCl3) δ (ppm): 175.0 (C=O), 174.8 (C=O), 164.5 (C=N), 164.3 (C=N), 51.9, 42.5, 42.2, 33.8, 30.5, 29.8, 28.5, 28.0, 26.5; HRMS (ESI) m / z 7H 11 NO3[M+Na] + Theoretical value is 180.0631, measured value is 180.0634.

[0195] Embodiment 39

[0196] Synthesize (Z / E)-3-(oxime)-2-cyclopentyl acetate methyl ester with the following structural formula

[0197]

[0198] In Example 29, the cyclododecane used was replaced by an equal molar amount of 2-cyclopentyl acetate methyl ester, and the other steps were the same as in Example 29 to obtain 142 mg of a (Z / E)-3-(oxime)-2-cyclopentyl acetate methyl ester mixture (E / Z=1.6:1) with a yield of 83%. The hydrogen spectrum data of the main isomer (E)-3-(oxime)-2-cyclopentyl acetate methyl ester are: 1H NMR (400MHz, CDCl3) δ (ppm): 9.40 (brs, 1H, N-OH), 3.65 (s, 3H), 2.65-2.54 (m, 2H), 2.46-2.32 (m, 4H), 2.08-1.94 (m, 2H), 1.43-1.30 (m, 1H); The hydrogen spectrum data of the minor isomer (Z)-3-(oxime)-2-cyclopentyl acetate are: 1 HNMR (400MHz, CDCl3) δ (ppm): 9.40 (brs, 1H, N-OH), 3.65 (s, 3H), 2.83-2.77 (m, 2H), 2.46-2.32 (m, 4H), 2.08-1.94 (m, 2H), 1.43-1.30 (m, 1H); (Z / E)-3-(oxime)cyclopentyl acetate methyl ester mixture carbon spectrum data are: 13 C NMR (100MHz, CDCl3) δ (ppm): 173.00 (C=O), 172.99 (C=O), 165.72 (C=N), 165.55 (C= N),51.70,39.31,38.92,36.90,35.24,34.80,33.47,31.09,30.45,30.13,26.65.

Claims

1. A method for synthesizing oxime compounds by catalyzing carbon-hydrogen bond oxidation with a tetradentate nitrogen-containing coordinated manganese, characterized in that: Under the conditions of a tetradentate nitrogen-containing coordinated manganese as a catalyst and an organic carboxylic acid as an additive, the carbon-hydrogen bond of the hydrocarbon compound represented by formula I or I′ or I" or I′" or I′"′ or I′"′′ is oxidized with H2O2 as an oxidant and oximated with hydroxylamine or hydroxylamine hydrochloride or hydroxylamine sulfate, and the oximation product is separated and purified after alkalization to obtain an oxime compound represented by formula II or II′ or II" or II′" or II′"′ or I′"′′; In the formula, R represents any one of hydrogen, halogen, methyl, methoxy, protected amine, and nitro, and R′ represents hydrogen, C1-C 10 Any of the alkyl groups, FG represents C1~C 10 Alkyl, C1~C 10 Alkoxy, phenyl, halogen, cyano, protected amine, C1~C 10 Any of the alkylamine and protected amino acid groups, FG' represents C1~C 10 Alkyl, C1~C 10 Alkoxy, protected amine, C1~C 10 Any one of an alkylamino group and a protected amino acid group; n is an integer of 0 to 15; The tetradentate nitrogen-containing coordinated manganese is any one of formula A or B: In formula A, X represents the coordinated anion Cl - Br - ,I - ,OAc - , OTf - Any one of the above, where Y in formula B represents the uncoordinated anion ClO4 - 、NO3 - , BF4 - PF6 - 、SbF6 - Any one of the following, m=2, or Y represents SO4 2- , m=1; in formula A or formula B Structural representation Any of Structural representation Any one of R 1 , R 2 , R 3 , R 4 Each independently represents H, C1~C 10 Any of an alkyl group and a silane group.

2. The method for synthesizing oxime compounds by catalyzing carbon-hydrogen bond oxidation with a tetradentate nitrogen-containing coordinated manganese according to claim 1, characterized in that: The tetradentate nitrogen-containing coordinated manganese is any one of formulas A-1 to A-5: 。 3. The method for synthesizing oxime compounds by catalyzing carbon-hydrogen bond oxidation with a tetradentate nitrogen-containing coordinated manganese according to claim 1, characterized in that: The organic carboxylic acid is any one of acetic acid, propionic acid, butyric acid and amino acid.

4. The method for synthesizing oxime compounds by catalyzing carbon-hydrogen bond oxidation with a tetradentate nitrogen-containing coordinated manganese according to any one of claims 1 to 3, characterized in that: The added amount of the tetradentate nitrogen-containing coordinated manganese is 0.01% to 5% of the molar amount of the hydrocarbon.

5. The method for synthesizing oxime compounds by catalyzing carbon-hydrogen bond oxidation with a tetradentate nitrogen-containing coordinated manganese according to any one of claims 1 to 3, characterized in that: The added amount of the hydroxylamine or hydroxylamine hydrochloride or hydroxylamine sulfate is 0.2 to 5 times the molar amount of the hydrocarbon.

6. The method for synthesizing oxime compounds by catalyzing carbon-hydrogen bond oxidation with a tetradentate nitrogen-containing coordinated manganese according to any one of claims 1 to 3, characterized in that: The amount of H2O2 added is 1 to 15 times the molar amount of the hydrocarbon.

7. The method for synthesizing oxime compounds by catalyzing carbon-hydrogen bond oxidation with a tetradentate nitrogen-containing coordinated manganese according to any one of claims 1 to 3, characterized in that: The amount of the organic carboxylic acid added is 1 to 30 times the molar amount of the hydrocarbon.

8. The method for synthesizing oxime compounds by catalyzing carbon-hydrogen bond oxidation with a tetradentate nitrogen-containing coordinated manganese according to any one of claims 1 to 3, characterized in that: The reaction condition of the method is ice bath reaction for 30 to 300 minutes.

9. The method for synthesizing oxime compounds by catalyzing carbon-hydrogen bond oxidation with a tetradentate nitrogen-containing coordinated manganese according to any one of claims 1 to 3, characterized in that: The solvent used in the method is any one of tert-butyl alcohol, acetonitrile, acetone, ethyl acetate and trifluoroethanol.

10. The method for synthesizing oxime compounds by catalyzing carbon-hydrogen bond oxidation with a tetradentate nitrogen-containing coordinated manganese according to any one of claims 1 to 3, characterized in that: The alkalization is carried out by using sodium bicarbonate, and the alkalization temperature is from room temperature to 80°C.

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