CN114835660A - Preparation method of oxime ether - Google Patents

Preparation method of oxime ether Download PDF

Info

Publication number
CN114835660A
CN114835660A CN202210373220.3A CN202210373220A CN114835660A CN 114835660 A CN114835660 A CN 114835660A CN 202210373220 A CN202210373220 A CN 202210373220A CN 114835660 A CN114835660 A CN 114835660A
Authority
CN
China
Prior art keywords
oxime
preparation
ether
oxime ether
ethers
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN202210373220.3A
Other languages
Chinese (zh)
Other versions
CN114835660B (en
Inventor
涂梦
沈永淼
李志明
王艾
刘小睿
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Longgang Research Institute Of Zhejiang University Of Technology Co ltd
Zhejiang Sci Tech University ZSTU
Original Assignee
Longgang Research Institute Of Zhejiang University Of Technology Co ltd
Zhejiang Sci Tech University ZSTU
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Longgang Research Institute Of Zhejiang University Of Technology Co ltd, Zhejiang Sci Tech University ZSTU filed Critical Longgang Research Institute Of Zhejiang University Of Technology Co ltd
Priority to CN202210373220.3A priority Critical patent/CN114835660B/en
Publication of CN114835660A publication Critical patent/CN114835660A/en
Application granted granted Critical
Publication of CN114835660B publication Critical patent/CN114835660B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/04—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D307/18—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D307/20—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
    • C07D309/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
    • C07D309/08—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D309/10—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D313/00—Heterocyclic compounds containing rings of more than six members having one oxygen atom as the only ring hetero atom
    • C07D313/02—Seven-membered rings
    • C07D313/04—Seven-membered rings not condensed with other rings
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/584—Recycling of catalysts

Abstract

The invention belongs to the technical field of bactericide, pesticide and medicine synthesis, and particularly relates to a preparation method of oxime ether. The synthesis process is environment-friendly, the reaction system is mild, the raw materials are low in price and easy to obtain, and the method is suitable for large-scale industrial production.

Description

Preparation method of oxime ether
Technical Field
The invention belongs to the technical field of bactericide, pesticide and medicine synthesis, and particularly relates to a preparation method of oxime ether.
Background
The oxime ether and the derivative thereof are important chemical products and have important application in pesticides and medicines. Because of its advantages of high efficiency, low toxicity and low residue, it is often used as an effective group for preparing important novel drugs and antibacterial agents. There are some reports on the synthesis of oxime ethers. For example, in CN109369449A, ketoxime and organic base are proportionally added into a high-pressure reactor, the reaction temperature is controlled between 10-60 ℃, an alkylating reagent is introduced for reaction for 2-6 hours, filtration is performed after the reaction is finished, and the filtrate is desolventized and crystallized to obtain oxime ether, wherein the yield is about 85%. In EP0158159, a water phase step-by-step process is adopted, namely ketoxime and sodium hydroxide are reacted to obtain oxime sodium salt, then an alkylating reagent is added for alkylation reaction, and after the reaction is finished, extraction and rectification are carried out to obtain an oxime ether product. The process route is relatively complex, the operation is more complicated, the production cost is high, and the post-treatment is relatively complex. In 2016, the Articima task group developed that oxime and tetrahydrofuran are used as raw materials, and dehydrogenation cross-coupling reaction is carried out through CuI catalysis, so that the construction of oxime ether bonded by C-O is realized. Although the reaction has simple process flow, the metal catalyst is used, so that metal residues are easy to remain during waste liquid treatment, and certain harm is caused to the environment and human bodies. Therefore, the market needs a synthesis process of oxime ether with simple reaction system, mild reaction and low cost.
Disclosure of Invention
Aiming at the problems in the prior art, the invention solves the difficulties of the prior art, provides a safe, green and simple-operation oxime ether preparation method, and constructs C-O to be bonded into oxime ether by utilizing visible light-mediated metal-free catalysis.
In order to achieve the technical purpose, the technical scheme of the invention is as follows:
a preparation method of oxime ether is disclosed, wherein the structure of the oxime ether is shown as formula (1):
Figure BDA0003589382710000011
wherein, R is 1 Using P-Ph, P-Cl, P-F, P-C (CH) 3 ) 3 、P-OMe、P-CH 3 、P-CF 3 、O,P-(CH 3 ) 2 、O,M,P-F 5 、Syn-(CH 3 ) 3 And Ph;
the R is 2 By CH 3 、CH 2 CH 3 、Ph-CH 3 H, Oxohexane, 4-Cl-Ph, 4-F-Ph, 4-Me-Ph, (CH) 2 ) 2 CH 3 One of (1);
said R is taken
Figure BDA0003589382710000021
Figure BDA0003589382710000022
One kind of (1).
Furthermore, the oxime ether is prepared by a method containing R 1 、R 2 The method comprises the steps of taking ketoxime or aldoxime as a raw material, adding an alkylating agent and a water removing agent, taking carbon tetrabromide as a catalyst, catalytically abstracting hydrogen of the alkylating agent through bromine free radicals generated by the carbon tetrabromide under the conditions of organic solvent and visible light irradiation, and carrying out single electron transfer on the generated free radicals and electrophilic substitution reaction with oxime to obtain an oxime ether product.
The raw material adopts ketoxime or aldoxime of R1 and R2 groups, and further adopts one of acetophenone oxime, p-chlorobenzophenone oxime, p-trifluorobenzaldehyde oxime, benzophenone oxime, 2, 4-dimethylbenzaldehyde oxime, p-methylbenzaldehyde oxime and phenylacetone oxime.
The alkylating reagent is one of cyclohexene oxide, tetrahydrofuran, 2-methyltetrahydrofuran and tetrahydropyran.
The organic solvent is one of n-butyl acetate, ethyl acetate, tetrahydrofuran, ethanol and toluene.
The reaction time is 4-6 h.
The dosage of the carbon tetrabromide is 0-2.0 eq.
The water removal agent is one of anhydrous magnesium sulfate and a 4A molecular sieve.
The purification method of the oxime ether product is that after the reaction is finished, petroleum ether and ethyl acetate are used as developing agents, column chromatography is used for separation, and drying is carried out after exsolution and concentration.
Carbon tetrabromide is used as a cheap and easily synthesized organic small molecular reagent, and can lead C-Br bonds to generate homologous cracking under the condition of heating or illumination to generate high-activity bromine free radicals. It is generally very chemoselective and regioselective and exhibits very good reactivity towards the cross-dehydrocoupling reaction (CDC).
From the above description, it can be seen that the present invention has the following advantages:
1. the invention solves the difficulty of the prior art, provides a safe, green and simple-operation oxime ether preparation method, and constructs C-O bonding oxime ether by utilizing visible light-mediated metal-free catalysis.
2. Under the condition of visible light, the method synthesizes oxime ether by the cross dehydrogenation coupling reaction of carbon tetrabromide catalytic oxime and an alkylating reagent, and uses the carbon tetrabromide to replace a complex catalytic system of metal, so that the method has the advantages of low cost, mild reaction condition, short time, easy treatment and the like.
3. The method is carried out at normal temperature by utilizing visible light, has mild reaction conditions, avoids potential safety hazards caused by high-temperature reaction, is easy to control the reaction, and is simple in reaction operation process and post-treatment.
4. The process provided by the invention is environment-friendly, is more suitable for industrial production, can be used for reducing the preparation cost and simultaneously obtaining products with high yield and high purity, and has better ecological advantages and economic advantages.
Drawings
FIG. 1 is a nuclear magnetic hydrogen spectrum of the oxime ether prepared in example 1.
FIG. 2 is a nuclear magnetic carbon spectrum of the oxime ether prepared in example 1.
FIG. 3 is a nuclear magnetic hydrogen spectrum of the oxime ether prepared in example 2.
FIG. 4 is a nuclear magnetic carbon spectrum of the oxime ether prepared in example 2.
FIG. 5 is a nuclear magnetic hydrogen spectrum of the oxime ether prepared in example 3.
FIG. 6 is a nuclear magnetic carbon spectrum of the oxime ether prepared in example 3.
FIG. 7 is a nuclear magnetic hydrogen spectrum of the oxime ether prepared in example 4.
FIG. 8 is a nuclear magnetic carbon spectrum of the oxime ether prepared in example 4.
FIG. 9 is a nuclear magnetic hydrogen spectrum of the oxime ether prepared in example 5.
FIG. 10 is a nuclear magnetic carbon spectrum of the oxime ether prepared in example 5.
FIG. 11 is a nuclear magnetic hydrogen spectrum of the oxime ether prepared in example 6.
FIG. 12 is a nuclear magnetic carbon spectrum of the oxime ether prepared in example 6.
FIG. 13 is a nuclear magnetic hydrogen spectrum of the oxime ether prepared in example 7.
FIG. 14 is a nuclear magnetic carbon spectrum of the oxime ether prepared in example 7.
FIG. 15 is a nuclear magnetic hydrogen spectrum of the oxime ether prepared in example 8.
FIG. 16 is a nuclear magnetic carbon spectrum of the oxime ether prepared in example 8.
FIG. 17 is a nuclear magnetic hydrogen spectrum of the oxime ether prepared in example 9.
FIG. 18 is a nuclear magnetic carbon spectrum of the oxime ether prepared in example 9.
FIG. 19 is a nuclear magnetic hydrogen spectrum of the oxime ether prepared in example 10.
FIG. 20 is a nuclear magnetic carbon spectrum of the oxime ether prepared in example 10.
Detailed Description
The embodiments of the present invention will be described in detail with reference to fig. 1 to 20, but the present invention is not limited to the claims.
Example 1
Anhydrous n-butyl acetate, benzophenone oxime (0.0197g, 0.1mmol, 1.0eq), anhydrous tetrahydrofuran (0.3606g, 50eq), carbon tetrabromide (0.0597g, 1.8eq), and 0.1000g molecular sieve were added in this order to a 5mL transparent glass reaction flask and mixed well. After the magneton was placed, the reaction flask was placed under argon gas for 15 minutes, and the reaction was carried out for 5 hours under the irradiation of a 3W LED blue lamp. After the reaction is finished, placing the reacted solution in a centrifuge tube for centrifugation, taking the supernatant liquid, and carrying out reduced pressure distillation and concentration by using a rotary evaporator to obtain a thick liquid. And finally, mixing ethyl acetate and petroleum ether in proportion as a developing agent, and performing column chromatography separation to obtain a product, wherein the yield is 87% after desolventizing and drying. As shown in fig. 1: 1 H NMR(400MHz,CDCl 3 ) δ 7.56-7.46 (m,2H), 7.44-7.37 (m,3H), 7.37-7.31 (m,4H),7.30(s,1H),5.91(dd, J ═ 5.3,1.3Hz,1H), 4.05-3.87 (m,2H), 2.11-1.75 (m, 4H). As shown in fig. 2: 13C NMR (101MHz, CDCl3) δ 158.15(s),136.49(s),133.55(s),129.35(d, J ═ 7.4Hz),128.68(s),128.16(d, J ═ 7.2Hz),127.91(s),106.70(s),77.38(s),77.06(s),76.74(s),67.98(s),30.71(s),23.88(s).
Examples 1 to 12 were prepared in the same manner as in example 1 except that the reaction time, the kind of organic solvent, the amount of carbon tetrabromide, etc. were adjusted and the influence on the reaction was examined, respectively.
Figure BDA0003589382710000041
Figure BDA0003589382710000051
As shown in the above table, in the synthesis of oxime ether, when the reaction time is 5h, the amount of carbon tetrabromide is 1.8eq based on the raw material, 4A molecular sieve is added, and butyl acetate is used as a solvent, the yield of oxime ether is the highest, and the yield is 87%.
Example 2
The pure p-trifluoromethylbenzaldehyde-O-2-tetrahydrofuryl oxime ether was obtained in 90% yield under the same conditions and by the same procedures as in example 1 except that 0.0189g of p-trifluoromethylbenzaldehyde oxime (0.1mmol) was used in place of 0.0197g of benzophenone oxime (0.1 mmol). As shown in fig. 3: 1 H NMR(400MHz,CDCl 3 ) δ 8.11(s,1H),7.72(d, J ═ 8.2Hz,2H),7.61(d, J ═ 8.3Hz,2H),5.90(dd, J ═ 5.0,1.5Hz,1H), 4.07-3.93 (m,2H), 2.18-2.02 (m,3H),1.93(dt, J ═ 9.5,4.6Hz, 1H). As shown in fig. 4: 13 C NMR(101MHz,CDCl 3 )δ148.54(s),135.59(s),125.57(dd,J＝7.5,3.7Hz),107.00(s),77.36(s),77.04(s),76.73(s),68.14(s),30.82(s),23.77(s)。
Example 3
The same procedures and conditions as in example were repeated except that 0.0149g of 2, 4-dimethylbenzaldehyde oxime (0.1mmol) was used in place of 0.0197g of benzophenone oxime (0.1mmol)1, the pure product was obtained as 2, 4-dimethylbenzaldehyde-O-2-tetrahydrofuryl oxime ether in 93% yield. As shown in fig. 5: 1 H NMR(400MHz,CDCl 3 ) δ 8.32(s,1H),7.64(d, J ═ 7.8Hz,1H),6.99(d, J ═ 9.6Hz,2H), 5.92-5.86 (m,1H), 4.08-3.91 (m,2H),2.38(s,3H),2.31(s,3H), 2.16-2.00 (m,3H), 1.97-1.86 (m, 1H). As shown in fig. 6: 13 C NMR(101MHz,CDCl 3 )δ148.92(s),139.82(s),136.75(s),131.47(s),127.52(s),127.11(s),127.00(d,J＝20.8Hz),106.58(s),77.39(s),77.07(s),76.75(s),68.00(s),30.87(s),23.89(s),21.31(s),19.73(s)。
example 4
The pure product obtained in the same manner as in example 1 except that 0.0169g of p-chloroacetophenone oxime (0.1mmol) was used in place of 0.0197g of benzophenone oxime (0.1mmol) was p-chloroacetophenone-O-2-tetrahydrofuryl oxime ether in a yield of 91%. As shown in fig. 7: 1 H NMR(400MHz,CDCl 3 ) δ 7.61(d, J ═ 7.3Hz,2H),7.31(d, J ═ 7.3Hz,2H),5.89(d, J ═ 2.0Hz,1H),4.07 to 3.86(m,2H),2.20(s,3H),2.15 to 2.00(m,3H),1.97 to 1.84(m, 1H). As shown in fig. 8: 13 C NMR(101MHz,CDCl 3 )δ154.68(s),135.04(d,J＝16.1Hz),128.47(s),127.52(s),106.62(s),77.42(s),77.11(s),76.79(s),67.98(s),30.90(s),23.95(s),12.75(s)。
example 5
The pure product obtained in the same manner as in example 1 except that 0.0135g of p-methylbenzaldehyde oxime (0.1mmol) was used in place of 0.0197g of benzophenone oxime (0.1mmol) was 88% yield of p-methylbenzaldehyde-O-2-tetrahydrofuryl oxime ether. As shown in fig. 9: 1 H NMR(400MHz,CDCl 3 ) δ 8.05(s,1H),7.50(d, J ═ 8.1Hz,2H),7.16(d, J ═ 8.0Hz,2H), 5.90-5.84 (m,1H), 4.12-3.89 (m,2H),2.35(s,3H), 2.15-2.01 (m,3H),1.91(dd, J ═ 7.5,2.6Hz,1H), as shown in fig. 10: 13 C NMR(101MHz,CDCl 3 )δ150.08(s),140.16(s),129.33(s),127.27(s),106.56(s),77.38(s),77.06(s),76.74(s),67.91(d,J＝9.7Hz),30.83(s),23.86(s),21.47(s).
example 6
Substituting 0.0135g of acetophenone oxime (0.1mmol) for 0.0197g of benzophenone oxime (0.1mmol), and other conditions and proceduresIn the same manner as in example 1, the pure product was obtained as acetophenone-O-2-tetrahydrofuryl oxime ether in 93% yield. As shown in fig. 11: 1 H NMR(400MHz,CDCl 3 ) δ 7.68(dd, J ═ 6.7,3.0Hz,2H), 7.37-7.33 (m,3H), 6.08-5.81 (m,1H),3.99(ddd, J ═ 13.5,11.5,6.8Hz,2H),2.24(s,3H), 2.15-2.03 (m,3H), 1.96-1.85 (m,1H). as shown in fig. 12: 13 C NMR(101MHz,CDCl 3 )δ155.86(s),136.56(s),129.14(s),128.29(s),126.27(s),106.51(s),77.36(s),77.05(s),76.73(s),67.96(s),30.94(s),23.97(s),12.97(s).
example 7
The pure product was propiophenone-O-2-tetrahydrofuryl oxime ether in 83% yield under the same conditions and procedures as in example 1 except that 0.0149g of phenylacetone oxime (0.1mmol) was used in place of 0.0197g of benzophenone oxime (0.1 mmol). As shown in fig. 13: 1 H NMR(400MHz,CDCl 3 ) δ 7.67(dd, J ═ 6.8,3.0Hz,2H),7.35(dd, J ═ 5.0,1.8Hz,3H), 5.97-5.80 (m,1H),3.99(ddd, J ═ 13.4,11.6,6.8Hz,2H),2.75(qd, J ═ 7.6,3.3Hz,2H), 2.18-2.01 (m,3H),1.93(d, J ═ 1.2Hz,1H),1.14(t, J ═ 7.6Hz,3H), as shown in fig. 14: 13 C NMR(101MHz,CDCl 3 )δ160.84(s),135.55(s),129.08(s),128.34(s),126.47(s),106.43(s),77.36(s),77.04(s),76.73(s),67.87(s),30.91(s),23.92(s),20.44(s),11.18(s).
example 8
The same procedures and conditions as in example 1 were repeated except for using 0.0135g of acetophenone oxime (0.1mmol) in place of 0.0197g of benzophenone oxime (0.1mmol) and 0.1503g of cyclohexene oxide (15eq) in place of 0.3606g of tetrahydrofuran (50eq) to obtain acetophenone-O-2-epoxyhexy oxime ether in a yield of 50%. As shown in fig. 15: 1 H NMR(400MHz,CDCl 3 ) δ 7.68(dd, J ═ 6.5,2.9Hz,2H), 7.37-7.32 (m,3H),5.54(dd, J ═ 9.2,5.2Hz,1H), 3.94-3.84 (m,1H), 3.71-3.61 (m,1H),2.27(s,3H), 1.91-1.81 (m,2H), 1.81-1.35 (m,6H), as shown in fig. 16: 13 C NMR(101MHz,CDCl 3 )δ155.96(s),136.55(s),129.19(s),128.32(s),126.32(s),104.60(s),77.40(s),77.08(s),76.77(s),62.82(s),32.89(s),30.77(s),29.42(s),22.92(s),13.12(s).
example 9
0.0135g of acetophenone oxime (0.1mmol) was substituted0.0197g of benzophenone oxime (0.1mmol), 0.4307g (50eq) of tetrahydropyran instead of 0.3606g of tetrahydrofuran (50eq), and the other conditions and procedures were the same as in example 1 to obtain acetophenone-O-2-tetrahydropyranyloxime ether in a yield of 30%. As shown in fig. 17: : 1 H NMR(400MHz,CDCl 3 ) δ 7.70-7.66 (m,2H), 7.37-7.33 (m,3H),5.41(dd, J ═ 4.9,2.6Hz,1H),3.94(ddd, J ═ 10.8,7.7,3.0Hz,1H), 3.68-3.60 (m,1H),2.31(s,3H), 1.94-1.76 (m,3H),1.62(dd, J ═ 8.7,3.3Hz, 3H). As shown in fig. 18: 13 C NMR(101MHz,CDCl 3 )δ156.37(s),136.48(s),129.23(s),128.34(s),126.38(s),101.08(s),77.43(s),77.11(s),76.79(s),29.17(s),25.33(s),20.09(s),13.09(s)。
example 10
The same procedures and conditions as in example 1 were repeated except that 0.0135g of acetophenone oxime (0.1mmol) was used in place of 0.0197g of benzophenone oxime (0.1mmol) and 0.4301g of 2-methyltetrahydrofuran (50eq) was used in place of 0.3606g of tetrahydrofuran (50eq), to obtain acetophenone-O-2- (2-tetrahydrofuran) -based oxime ether in a yield of 37%. As shown in fig. 19: 1H NMR (400MHz, CDCl3) δ 7.68(dd, J ═ 6.8,3.0Hz,2H),7.35(dd, J ═ 5.0,1.8Hz,3H),5.85(d, J ═ 4.4Hz,1H),4.27(dd, J ═ 10.4,4.2Hz,1H),2.24(s,3H), 2.21-2.04 (m,3H), 1.79-1.67 (m,1H),1.34(d, J ═ 6.2Hz,3H), as shown in fig. 20: 13C NMR (101MHz, CDCl3) delta 155.35(s),136.66(s),129.08(s),128.29(s),126.26(s),106.77(s),77.38(s),77.07(s),76.75(s),32.31(s),31.38(s),22.71(s),13.03(s).
Example 11: amplification reaction of example 1
1.000g of benzophenone oxime (0.005mol),3.027g of carbon tetrabromide (1.8eq), 18.283g of tetrahydrofuran (50eq) and 1.000g of 4A molecular sieve were sequentially charged into a 100mL single-neck flask, and 50mL of anhydrous n-butyl acetate was added thereto and mixed uniformly. After the addition of magnetons, the flask was placed under argon gas for 30 minutes and reacted for 12 hours under irradiation of a 30W blue lamp. The working-up procedure after completion of the reaction was the same as in example 1, and the oxime was obtained in 85% yield.
The method takes ketoxime or aldoxime as a raw material, synthesizes oxime ether by the catalysis of the light-mediated carbon tetrabromide, has green and mild reaction conditions, avoids using a transition metal catalyst, has short reaction time and simple operation process, and can effectively replace the traditional oxime ether synthesis method. When benzophenone oxime and tetrahydrofuran are used as the basis, the optimum conditions are: the reaction time is 5h, the dosage of carbon tetrabromide is 1.8eq of the raw material, a 4A molecular sieve is added, and when butyl acetate is taken as a solvent, the yield of the obtained oxime ether is highest. Further, the substrate adaptability was developed under these conditions, and it can be seen from examples 2 to 5 that the substrate adaptability was good. And after the amplification reaction, the yield can reach 85 percent, and the method is very suitable for industrial production.
In the technical scheme, the yield of the oxime ether can reach 93 percent, which is higher than the highest yield (88 percent) of the oxime ether synthesized by catalyzing a metal catalyst CuI in the literature, and the acetophenone-O-2-tetrahydropyranyl oxime ether is obtained by reacting cyclohexene oxide with oxime, wherein the yield is 50 percent, and the reaction which cannot be completed by a CuI catalytic system can be realized. The method for synthesizing oxime ether by visible light mediated carbon tetrabromide catalysis can achieve good yield, has wide substrate adaptability and no metal residue, and has wider application prospect in the pharmaceutical field.
It should be understood that the detailed description of the invention is merely illustrative of the invention and is not intended to limit the invention to the specific embodiments described. It will be appreciated by those skilled in the art that the present invention may be modified or substituted equally as well to achieve the same technical result; as long as the use requirements are met, the method is within the protection scope of the invention.

Claims (10)

1. A method for preparing oxime ether is characterized in that: the oxime ether has a structure shown in formula (1):
Figure FDA0003589382700000011
wherein, R is 1 Using P-Ph, P-Cl, P-F, P-C (CH) 3 ) 3 、P-OMe、P-CH 3 、P-CF 3 、O,P-(CH 3 ) 2 、O,M,P-F 5 、Syn-(CH 3 ) 3 And Ph;
the R is 2 By CH 3 、CH 2 CH 3 、Ph-CH 3 H, Oxohexane, 4-Cl-Ph, 4-F-Ph, 4-Me-Ph, (CH) 2 ) 2 CH 3 One of (1);
said R is taken
Figure FDA0003589382700000012
Figure FDA0003589382700000013
One kind of (1).
2. The process for the preparation of oxime ethers of claim 1 wherein: the preparation method of the oxime ether is to add an alkylating reagent and a water removing agent into raw materials of China, take carbon tetrabromide as a catalyst, and obtain the oxime ether under the irradiation conditions of an organic solvent and visible light.
3. The process for preparing an oxime ether according to claim 2, which comprises: the raw material adopts ketoxime or aldoxime corresponding to R1 and R2 groups.
4. The process for preparing oxime ethers of claim 3 wherein: the raw material adopts one of acetophenone oxime, p-chlorobenzophenone oxime, p-trifluorobenzaldehyde oxime, benzophenone oxime, 2, 4-dimethylbenzaldehyde oxime, p-methylbenzaldehyde oxime and phenylacetone oxime.
5. The process for the preparation of oxime ethers of claim 2 wherein: the alkylating reagent is one of cyclohexene oxide, tetrahydrofuran, 2-methyltetrahydrofuran and tetrahydropyran.
6. The process for the preparation of oxime ethers of claim 2 wherein: the organic solvent is one of n-butyl acetate, ethyl acetate, tetrahydrofuran, ethanol and toluene.
7. The process for the preparation of oxime ethers of claim 2 wherein: the reaction time is 4-6 h.
8. The process for the preparation of oxime ethers of claim 2 wherein: the dosage of the carbon tetrabromide is 0-2.0 eq.
9. The process for the preparation of oxime ethers of claim 2 wherein: the water removal agent adopts one of anhydrous magnesium sulfate and a 4A molecular sieve.
10. The process for preparing an oxime ether according to claim 2, which comprises: the purification method of the oxime ether product is that after the reaction is finished, petroleum ether and ethyl acetate are used as developing agents, column chromatography is used for separation, and drying is carried out after exsolution and concentration.
CN202210373220.3A 2022-04-11 2022-04-11 Preparation method of oxime ether Active CN114835660B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210373220.3A CN114835660B (en) 2022-04-11 2022-04-11 Preparation method of oxime ether

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210373220.3A CN114835660B (en) 2022-04-11 2022-04-11 Preparation method of oxime ether

Publications (2)

Publication Number Publication Date
CN114835660A true CN114835660A (en) 2022-08-02
CN114835660B CN114835660B (en) 2024-03-22

Family

ID=82564280

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210373220.3A Active CN114835660B (en) 2022-04-11 2022-04-11 Preparation method of oxime ether

Country Status (1)

Country Link
CN (1) CN114835660B (en)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0158159A1 (en) * 1984-04-12 1985-10-16 AlliedSignal Inc. Process for the synthesis of o-substituted oxime compounds and the conversion thereof into the corresponding hydroxylamine o-substituted
CN109369449A (en) * 2018-12-25 2019-02-22 浙江工业大学 A kind of method of synthesizing oxime ether

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0158159A1 (en) * 1984-04-12 1985-10-16 AlliedSignal Inc. Process for the synthesis of o-substituted oxime compounds and the conversion thereof into the corresponding hydroxylamine o-substituted
CN109369449A (en) * 2018-12-25 2019-02-22 浙江工业大学 A kind of method of synthesizing oxime ether

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
H. JU HAN等: "Synthesis and biological activity of selenopsammaplin A and its analogues as antitumor agents with DOT1L inhibitory activity", 《BIOORG. MED. CHEM.》, vol. 35, pages 116072 *
IVOR SMAJLAGIC等: "Organocatalysis Linked to Charge-Enhanced Acidity with Superelectrophilic Traits", 《ACS CATAL.》, vol. 12, pages 1128 - 1138 *
ZHI-HUI REN等: "CuI-catalyzed oxidative cross coupling of oximes with tetrahydrofuran: a direct access toOtetrahydrofuran-2-yl oxime ethers", 《RSC ADV.》, vol. 6, pages 16516 - 16519 *

Also Published As

Publication number Publication date
CN114835660B (en) 2024-03-22

Similar Documents

Publication Publication Date Title
CN106892935B (en) A kind of immobilized copper catalysis of chitosan prepares the method and application of organoboron compound
Cheng et al. Palladium catalyzed acetoxylation of benzylic C–H bonds using a bidentate picolinamide directing group
CN110590819B (en) Process for producing organoboron compound and process for producing beta-hydroxyorganoboron compound
Shi et al. Nickel catalyzed reduction of arenols under mild conditions
CN104262071A (en) Photocatalysis synthesis method of biphenyl compounds
CN112441875B (en) Method for copper photocatalytic synthesis of 9-trifluoromethyl-9, 10-dihydrophenanthrene compound
CN113461597B (en) Preparation method of nilaparib intermediate
CN114835660A (en) Preparation method of oxime ether
Liu et al. A New Formal Synthetic Route to Entecavir
CN112778351B (en) Preparation method of beta-dimethylphenyl silicon substituted aromatic nitro compound
CN110317170B (en) Green synthesis method of 3-phenanthridinyl propyl formate compound
CN108948055B (en) 8-methylquinoline gem-diboron compound and preparation method thereof
CN110845291B (en) Method for catalytic reduction of alkyne into olefin by visible light induction
Shao et al. Bioinspired Total Synthesis of Cephalotaxus Diterpenoids and Their Structural Analogues
CN114213443B (en) Method for preparing alkyl boron ester from alkenyl boron ester
CN111302880B (en) Application of iron catalyst in reduction coupling reaction and preparation method of aromatic ring and heterocyclic derivative
CN114773354B (en) Simple synthesis method of Trisphaeridine
CN111848483B (en) Asymmetric catalytic preparation method of brivaracetam
CN114933624B (en) Artificial synthesis method of natural product (+) -digitonin
CN110642770B (en) Preparation method of 5-methoxyindole
CN110256210B (en) Preparation method of 1,2, 3-trimethoxy-4-benzyl benzene
CN116217625A (en) CNC (computer numerical control) tridentate ruthenium complex as well as preparation method and application thereof
CN107445879B (en) Preparation method of Latricinib intermediate
CN108101797B (en) Method for synthesizing o-aminobenzaldehyde
CN1970517A (en) Method for synthesizing hang type dicyclopentadiene catalyzed by molecular sieve

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
CB02 Change of applicant information

Address after: 325802 floor 3, building 2, printing industry innovation service complex, Century Avenue (Chengdong Industrial Park), Longgang City, Wenzhou City, Zhejiang Province

Applicant after: ZHEJIANG SCI-TECH University

Applicant after: Longgang Research Institute of Zhejiang University of Technology Co.,Ltd.

Address before: No.928, No.2 Baiyang street, Hangzhou Economic and Technological Development Zone, Hangzhou, Zhejiang 310000

Applicant before: ZHEJIANG SCI-TECH University

Applicant before: Longgang Research Institute of Zhejiang University of Technology Co.,Ltd.

CB02 Change of applicant information
GR01 Patent grant
GR01 Patent grant