CN109988091B - Preparation method of imine compound - Google Patents
Preparation method of imine compound Download PDFInfo
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- CN109988091B CN109988091B CN201910318935.7A CN201910318935A CN109988091B CN 109988091 B CN109988091 B CN 109988091B CN 201910318935 A CN201910318935 A CN 201910318935A CN 109988091 B CN109988091 B CN 109988091B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D207/20—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07—ORGANIC CHEMISTRY
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- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/82—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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Abstract
The invention discloses a preparation method of an imine compound, which comprises the steps of adding oxime ether and a metal simple substance into a reaction vessel in a one-pot manner under anhydrous and anaerobic conditions, taking tetrahydrofuran as a solvent, initiating by using an iodine simple substance at high temperature, carrying out an inert gas protection reaction, reacting for 4 hours at 60 ℃, detecting the reaction progress by using a TLC plate, carrying out water quenching reaction, extracting by using ethyl acetate, washing by using saturated salt, drying by using anhydrous sodium sulfate, and carrying out column chromatography purification by using alkaline alumina to obtain a product. The method is simple and efficient, and can be used for promoting gamma-bromooxime ether and delta-bromooxime ether to carry out intramolecular cyclization by utilizing rare earth metals of samarium and ytterbium, so that the target compound can be synthesized with a yield on the upper middle level.
Description
Technical Field
The present invention relates to a method for producing an imine compound.
Background
Imine structures are not only ubiquitous in Natural product molecules (Journal of Natural Products,1994,57,4, 528-containing 533.), but are also the key backbone of many drug molecules (ACS Catal.2013,3, 1752-containing 1755). For example, MLN8237 is an Aurora-A kinase inhibitor and is useful in the treatment of epithelial ovarian cancer, fallopian tube cancer and primary peritoneal cancer. The small molecule (+) -JQ1 was reported by the doctris Haldar doctor study and is an effective drug for the treatment of heart failure (sci. trans. med.,2017,9, eaah 5084.). Myosmine is a natural tobacco alkaloid (J.Med.chem.1987,30, 1433-. E7016 is a PARP inhibitor that treats many cancers by targeting the DNA damage repair mechanism (Biochemistry,2014,53, 1779-. Furthermore, imines are also important precursors for the preparation of pyrrole compounds (ACS Catal.2016,6, 3880-3889). Therefore, its importance has attracted extensive attention by chemists and medical scientists. From the prior literature reports, the methods for synthesizing imine compounds can be roughly divided into the following methods: (1) the organic metal reagent reacts with 4-chlorobutyronitrile or amide, and the method has low applicability because the reaction substrate is difficult to synthesize; (2) aza-witting reaction of azido alkyl ketone, wherein the reaction takes azide as raw material and has certain danger; (3) the complexes such as palladium, rhodium and the like catalyze alkenyl amine or alkynyl amine to synthesize imine, but the yield is not optimistic and the economic cost is higher; (4) the complex formed by the transition metal cation catalyzes various oxime structures to generate amino-Heck. Although the method has high yield, the method has higher requirements on reaction conditions; (5) although such methods as microwave irradiation or photochemical methods are environmentally friendly, they have certain difficulties in handling.
Disclosure of Invention
The present invention has been made to solve the above problems, and an object of the present invention is to provide a method for producing an imine compound.
The technical scheme of the invention is as follows:
a method of preparing an imine compound, the method comprising: under anhydrous and anaerobic conditions, adding oxime ether and a metal simple substance into a reaction vessel in a one-pot manner, initiating at high temperature by using tetrahydrofuran as a solvent and using an iodine simple substance, carrying out an inert gas protection reaction at 60 ℃ for 4 hours, detecting the reaction progress by using a TLC plate, quenching the reaction by using water, extracting by using ethyl acetate, washing by using saturated salt, drying by using anhydrous sodium sulfate, and carrying out column chromatography purification by using alkaline alumina to obtain the product.
Further, the oxime ether is selected from the group consisting of 4-bromo-1-phenylbutan-1-one O-methyloxime, 4-bromo-1- (p-tolyl) butan-1-one O-methyloxime, 4-bromo-1- (4-methoxyphenyl) butan-1-one O-methyloxime, 4-bromo-1- (4-ethylphenyl) butan-1-one O-methyloxime, 4-bromo-1- (4- (tert-butyl) phenyl) butan-1-one O-methyloxime, 4-bromo-1- (3, 4-dimethoxyphenyl) butan-1-one O-methyloxime, 4-bromo-1- (3-bromo-4-methoxyphenyl) butan-1-one O-methyloxime, and mixtures thereof, 4-bromo-1- (4-fluorophenyl) butan-1-one O-methyloxime, 4-bromo-1- (5-bromothien-2-yl) butan-1-one O-methyloxime, 4-bromo-1- (naphthalen-2-yl) butan-1-one O-methyloxime, 4-bromo-1-phenylbutan-1-one O-benzyloxime, 5-bromo-1-phenylpentan-1-one O-methyloxime, 5-bromo-1- (4-ethylphenyl) pentan-1-one O-methyloxime, 5-bromo-1- (4-methoxyphenyl) pentan-1-one O-methyloxime, any one of 5-bromo-1- (4-fluorophenyl) pent-1-one O-methyloxime or 5-bromo-1- (thiophen-2-yl) pent-1-one O-methyloxime.
Further, the molar ratio of the oxime ether to the metal simple substance is 1: 1.5.
further, the metal simple substance is samarium or ytterbium.
Further, the metal simple substance: tetrahydrofuran 0.75 mmol: 5 ml.
Further, the oxime ethers: tetrahydrofuran 0.5 mmol: 2 ml.
Further, the temperature of the high-temperature initiation is 60 ℃, and the reaction time is 4 h.
Further, the amount of water used for quenching the reaction with water was 2 ml.
Further, the alkaline alumina is 200-300 meshes.
The invention provides a preparation method of an imine compound, which has the advantages that: the method is simple and efficient, and can be used for promoting gamma-bromooxime ether and delta-bromooxime ether to carry out intramolecular cyclization by utilizing rare earth metals of samarium and ytterbium, so that the target compound can be synthesized with a yield on the upper middle level.
Detailed Description
In order to make the aforementioned objects, features and advantages of the present invention comprehensible, embodiments accompanied with figures are described in detail below. The invention is not limited to the embodiments listed but also comprises any other known variations within the scope of the invention as claimed.
Reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic may be included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
Example 1
The present embodiment shows a method for preparing an imine compound according to the following steps: adding freshly ground samarium or ytterbium (0.75mmol) into a 25-ml round-bottom flask, and vacuumizing for three times under the protection of nitrogen. 5ml of tetrahydrofuran which had been distilled off was taken out by a syringe and charged into the flask, and then 4-bromo-1-phenylbutan-1-one O-methyloxime (0.5mmol) was dissolved in 2ml of tetrahydrofuran and charged into the system. Taking a small particle of iodine, initiating the reaction at high temperature, stirring for 4 hours at 60 ℃, and monitoring the reaction progress by a TLC plate. After the reaction is finished, quenching the reaction by using 2ml of water, extracting by using ethyl acetate, washing by using saturated salt solution, drying by using anhydrous sodium sulfate, carrying out column chromatography by using 200-mesh 300-mesh alkaline alumina, and separating to obtain the 5-phenyl-3, 4-dihydro-2H-pyrrole. The yield is Sm 60% and Yb 70%.
1H NMR(400MHz,CDCl3)δ7.98–7.74(m,2H),7.41(dd,J＝5.1,1.9Hz,3H),4.15–4.00(m,2H),3.02–2.84(m,2H),2.03(dt,J＝15.3,7.6Hz,2H)ppm；13C NMR(101MHz,CDCl3)δ173.43,134.71,130.42,128.53,127.71,61.64,35.03,22.78ppm；HRMS(CI)m/z[M+H]+calcd for C10H12N 144.0813,found 144.0812。
Example 2
The present embodiment shows a method for preparing an imine compound according to the following steps: using a method similar to that in example 1, 4-bromo-1- (p-tolyl) butan-1-one O-methyloxime was used in place of 4-bromo-1-phenylbutan-1-one O-methyloxime in example 1 to give 5- (p-tolyl) -3, 4-dihydro-2H-pyrrole in a yield of Sm 70% and Yb 77%.
1H NMR(400MHz,CDCl3)δ7.74(d,J＝8.1Hz,2H),7.21(d,J＝8.0Hz,2H),4.05(dd,J＝10.1,4.6Hz,2H),2.93(dd,J＝11.5,4.9Hz,2H),2.38(s,3H),2.03(dd,J＝8.4,7.4Hz,2H)ppm；13C NMR(101MHz,CDCl3)δ173.40,140.70,131.93,129.26,127.73,61.45,35.01,22.75,21.56ppm；HRMS(CI)m/z[M+H]+calcd for C11H14N 159.1048,found159.1042。
Example 3
The present embodiment shows a method for preparing an imine compound according to the following steps: by a similar synthesis procedure, 4-bromo-1- (4-methoxyphenyl) butan-1-one O-methyloxime was used instead of 4-bromo-1-phenylbutan-1-one O-methyloxime as in example 1, giving 5- (4-methoxyphenyl) -3, 4-dihydro-2H-pyrrole in a yield of Sm 69% and Yb 78%.
1H NMR(400MHz,CDCl3)δ7.80(d,J＝8.8Hz,2H),6.92(d,J＝8.9Hz,2H),4.04(t,J＝7.3Hz,2H),3.84(s,3H),3.00–2.87(m,2H),2.02(dt,J＝15.1,7.6Hz,2H)ppm；13C NMR(101MHz,CDCl3)δ172.81,161.47,129.36,127.48,113.85,61.35,55.44,34.96,22.82ppm；HRMS(CI)m/z[M+H]+calcd for C11H14NO 176.1075,found 176.1068。
Example 4
The present embodiment shows a method for preparing an imine compound according to the following steps: in a similar manner, 4-bromo-1- (4-ethylphenyl) butan-1-one O-methyloxime was used in place of 4-bromo-1-phenylbutan-1-one O-methyloxime in example 1 to give 5- (4-ethylphenyl) -3, 4-dihydro-2H-pyrrole in an Sm 86% yield; yb 90 percent.
1H NMR(400MHz,CDCl3)δ7.76(d,J＝8.2Hz,2H),7.23(d,J＝8.3Hz,2H),4.05(t,J＝7.3Hz,2H),2.92(dd,J＝8.9,7.6Hz,2H),2.68(d,J＝7.6Hz,2H),2.02(dd,J＝8.5,7.4Hz,2H),1.25(t,J＝7.6Hz,3H)ppm；13C NMR(101MHz,CDCl3)δ173.28,146.87,132.25,128.02,127.76,61.53,35.01,28.88,22.77,15.49ppm；HRMS(CI)m/z[M+H]+calcd for C12H16N 174.1283,found 174.1283。
Example 5
The present embodiment shows a method for preparing an imine compound according to the following steps: in a similar manner, 4-bromo-1- (4- (tert-butyl) phenyl) butan-1-one O-methyloxime was used in place of 4-bromo-1-phenylbutan-1-one O-methyloxime in example 1 to give 5- (4- (tert-butyl) phenyl) -3, 4-dihydro-2H-pyrrole in a yield of Sm 85%; yb 95 percent.
1H NMR(400MHz,CDCl3)δ7.78(d,J＝8.5Hz,2H),7.42(d,J＝8.5Hz,2H),4.05(t,J＝7.3Hz,2H),2.96–2.89(m,2H),2.01(dq,J＝15.0,7.6Hz,2H),1.33(s,9H)ppm；13C NMR(101MHz,CDCl3)δ173.18,153.70,131.94,127.51,125.43,61.53,34.99,34.91(s),31.31,22.76ppm；HRMS(CI)m/z[M+H]+calcd for C14H20N 202.1596,found 202.1594。
Example 6
The present embodiment shows a method for preparing an imine compound according to the following steps: in a similar manner, 4-bromo-1- (3, 4-dimethoxyphenyl) butan-1-one O-methyloxime was used in place of 4-bromo-1-phenylbutan-1-one O-methyloxime in example 1 to give 5- (3, 4-dimethoxyphenyl) -3, 4-dihydro-2H-pyrrole in a yield of Sm 70%; yb 82%.
1H NMR(400MHz,CDCl3)δ7.57(d,J＝1.9Hz,1H),7.26(dd,J＝8.6,2.2Hz,1H),6.86(d,J＝8.3Hz,1H),4.05(t,J＝7.3Hz,2H),3.94(s,3H),3.92(s,3H),3.02–2.81(m,2H),2.13–1.95(m,2H)ppm；13C NMR(101MHz,CDCl3)δ172.92,151.13,149.07,127.85,121.58,110.30,109.53,61.45,56.06,56.02,34.90,22.93ppm；HRMS(CI)m/z[M+H]+calcd for C12H16NO2 206.1181,found 206.1174。
Example 7
The present embodiment shows a method for preparing an imine compound according to the following steps: in a similar manner, 4-bromo-1- (3-bromo-4-methoxyphenyl) butan-1-one O-methyloxime was used instead of 4-bromo-1-phenylbutan-1-one O-methyloxime in example 1 to give 5- (3-bromo-4-methoxyphenyl) -3, 4-dihydro-2H-pyrrole in yield: sm 56%; 68 percent of Yb.
1H NMR(400MHz,CDCl3)δ8.05(s,1H),7.75(d,J＝8.0Hz,1H),6.90(d,J＝8.3Hz,1H),4.04(s,2H),3.93(s,3H),2.87(d,J＝7.0Hz,2H),2.21–1.85(m,2H)ppm；13C NMR(101MHz,CDCl3)δ171.60,157.45,132.78,128.77,128.16,111.76,111.41,61.46,56.39,34.89,22.80ppm；HRMS(CI)m/z[M+H]+calcd for C11H13BrNO 254.0181,found 254.0175。
Example 8
The present embodiment shows a method for preparing an imine compound according to the following steps: in a similar manner, 4-bromo-1- (4-fluorophenyl) butan-1-one O-methyloxime was used instead of 4-bromo-1-phenylbutan-1-one O-methyloxime in example 1 to give 5- (4-fluorophenyl) -3, 4-dihydro-2H-pyrrole in yield: sm 89%; yb 96%.
1H NMR(400MHz,CDCl3)δ8.01–7.67(m,2H),7.16–6.98(m,2H),4.05(t,J＝7.3Hz,2H),3.04–2.80(m,2H),2.04(td,J＝15.0,7.6Hz,2H)ppm；13C NMR(101MHz,CDCl3)δ172.19(s),164.20(1J(C,F)＝250.48Hz),131.08(4J(C,F)＝3.03Hz),129.70(2J(C,F)＝8.08Hz),115.52(3J(C,F)＝21.21Hz),61.66,35.07,22.89ppm；HRMS(CI)m/z[M+H]+calcd for C10H11FN 164.0876,found 164.0882。
Example 9
The present embodiment shows a method for preparing an imine compound according to the following steps: in a similar manner, 4-bromo-1- (5-bromothiophen-2-yl) butan-1-one O-methyloxime was used instead of 4-bromo-1-phenylbutan-1-one O-methyloxime in example 1 to give 5- (5-bromothiophen-2-yl) -3, 4-dihydro-2H-pyrrole in yield: sm 23%; yb 30%.
1H NMR(400MHz,CDCl3)δ7.03(q,J＝3.9Hz,2H),4.10–3.84(m,2H),2.97–2.73(m,2H),2.12–1.96(m,2H)ppm；13C NMR(101MHz,CDCl3)δ167.28,141.35,130.48,129.23,116.84,61.45,35.17,23.05ppm；HRMS(CI)m/z[M+H]+calcd for C8H9BrNS229.9639,found 229.9635。
Example 10
The present embodiment shows a method for preparing an imine compound according to the following steps: in a similar manner, 4-bromo-1- (naphthalen-2-yl) butan-1-one O-methyloxime was used instead of 4-bromo-1-phenylbutan-1-one O-methyloxime in example 1 to give 5- (naphthalen-2-yl) -3, 4-dihydro-2H-pyrrole in yield: sm 48%; yb 50%.
1H NMR(400MHz,CDCl3)δ8.21–8.01(m,2H),7.93–7.76(m,3H),7.51(dd,J＝6.4,2.7Hz,2H),4.12(t,J＝7.3Hz,2H),3.06(t,J＝8.2Hz,2H),2.09(dd,J＝15.8,7.7Hz,2H)ppm；13C NMR(101MHz,CDCl3)δ173.42,134.46,133.12,132.25,128.81,128.29,128.25,127.87,127.13,126.48,124.62,61.79,35.04,22.87ppm；HRMS(CI)m/z[M+H]+calcd for C14H14N 196.1126,found 196.1131。
Example 11
The present embodiment shows a method for preparing an imine compound according to the following steps: in a similar manner, 4-bromo-1-phenylbutan-1-one O-benzyl oxime was used instead of 4-bromo-1-phenylbutan-1-one O-methyl oxime in example 1 to give 5-phenyl-3, 4-dihydro-2H-pyrrole in yield: sm 33%; yb 40%.
1H NMR(400MHz,CDCl3)δ7.98–7.74(m,2H),7.41(dd,J＝5.1,1.9Hz,3H),4.15–4.00(m,2H),3.02–2.84(m,2H),2.03(dt,J＝15.3,7.6Hz,2H)ppm；13C NMR(101MHz,CDCl3)δ173.43,134.71,130.42,128.53,127.71,61.64,35.03,22.78ppm；HRMS(CI)m/z[M+H]+calcd for C10H12N 144.0813,found 144.0812。
Example 12
The present embodiment shows a method for preparing an imine compound according to the following steps: in a similar manner, 5-bromo-1-phenylpentan-1-one O-methyloxime was used in place of 4-bromo-1-phenylbutan-1-one O-methyloxime in example 1 to give 6-phenyl-2, 3,4, 5-tetrahydropyridine. The yield is Sm 56%; 60 percent of Yb.
1H NMR(400MHz,CDCl3)δ7.80–7.69(m,2H),7.41–7.31(m,3H),4.11–3.76(m,2H),2.61(ddd,J＝6.5,4.4,2.1Hz,2H),1.81(d,J＝6.3Hz,2H),1.73–1.59(m,2H)ppm；13C NMR(101MHz,CDCl3)δ165.71,140.24,129.54,128.24,125.93,77.48,77.16,76.84,49.91,27.07,21.90,19.79ppm；HRMS(CI)m/z[M+H]+calcd for C11H14N 160.1124,found160.1126。
Example 13
The present embodiment shows a method for preparing an imine compound according to the following steps: in a similar manner, 5-bromo-1- (4-ethylphenyl) pentan-1-one O-methyloxime was used in place of 4-bromo-1-phenylbutan-1-one O-methyloxime in example 1 to give 6- (4-ethylphenyl) -2,3,4, 5-tetrahydropyridine. The yield is Sm 53%; and Yb is 69 percent.
1H NMR(400MHz,CDCl3)δ7.68(d,J＝8.3Hz,2H),7.19(d,J＝8.3Hz,2H),3.81(ddd,J＝7.7,5.7,2.0Hz,2H),2.71–2.57(m,4H),1.81(d,J＝6.3Hz,2H),1.66(d,J＝6.0Hz,2H),1.23(t,J＝7.6Hz,3H)ppm；13C NMR(101MHz,CDCl3)δ165.53,145.92,137.86,127.79,125.99,49.94,28.75,27.08,22.03,19.91,15.57ppm；HRMS(CI)m/z[M+H]+calcd for C13H18N 188.1439,found 188.1432。
Example 14
The present embodiment shows a method for preparing an imine compound according to the following steps: in a similar manner, 5-bromo-1- (4-methoxyphenyl) pentan-1-one O-methyloxime was used in place of 4-bromo-1-phenylbutan-1-one O-methyloxime in example 1 to give 6- (4-methoxyphenyl) -2,3,4, 5-tetrahydropyridine. The yield is Sm 73%; yb 64 percent.
1H NMR(400MHz,CDCl3)δ7.81–7.63(m,2H),6.92–6.83(m,2H),3.83–3.77(m,5H),2.63–2.54(m,2H),1.81(dd,J＝7.6,4.6Hz,2H),1.69–1.60(m,2H)ppm；13C NMR(101MHz,CDCl3)δ164.85,160.81,132.99,127.40,113.50,55.35,49.77,26.90,22.00,19.90ppm；HRMS(CI)m/z[M+H]+calcd for C12H16NO 190.1232,found 190.1228。
Example 15
The present embodiment shows a method for preparing an imine compound according to the following steps: in a similar manner, 5-bromo-1- (4-fluorophenyl) pent-1-one O-methyloxime was used in place of 4-bromo-1-phenylbutan-1-one O-methyloxime in example 1 to give 6- (4-fluorophenyl) -2,3,4, 5-tetrahydropyridine. The yield is Sm 58%; 70% of Yb.
1H NMR(400MHz,CDCl3)δ7.85–7.59(m,2H),7.11–6.94(m,2H),3.87–3.74(m,2H),2.59(tt,J＝6.5,2.1Hz,2H),1.82(qd,J＝6.4,3.6Hz,2H),1.71–1.60(m,2H)ppm；13C NMR(101MHz,CDCl3)δ164.7(1J(C,F)＝56.7Hz),162.54,136.46(4J(C,F)＝3.13Hz),127.87(3J(C,F)＝8.38Hz),115.09(2J(C,F)＝21.11Hz),49.91,27.02,21.86,19.79ppm；HRMS(CI)m/z[M+H]+calcd for C11H13FN 178.1032,found 178.1034。
Example 16
The present embodiment shows a method for preparing an imine compound according to the following steps: in a similar manner, 5-bromo-1- (thiophen-2-yl) pentan-1-one O-methyloxime was used in place of 4-bromo-1-phenylbutan-1-one O-methyloxime in example 1 to give 6- (thiophen-2-yl) -2,3,4, 5-tetrahydropyridine. The yield is Sm 45%; yb 50%.1H NMR(400MHz,CDCl3)δ7.36(dd,J＝5.1,0.9Hz,1H),7.32(d,J＝4.1Hz,1H),7.06(dd,J＝5.0,3.7Hz,1H),3.82(ddd,J＝7.6,5.6,1.9Hz,2H),2.68(tt,J＝6.6,2.0Hz,2H),1.93–1.81(m,2H),1.76–1.65(m,2H)ppm；13C NMR(101MHz,CDCl3)δ161.24,146.90,127.95,127.26,125.63,49.63,27.17,22.13,19.53ppm；HRMS(CI)m/z[M+H]+calcd for C9H12NS 166.0685,found166.0685.。
Note that: (1) the present invention reports a method; (2) reacting an organometallic reagent with 4-chlorobutyronitrile or amide; (3) aza-witting reaction of azido alkyl ketone; (4) the complexes such as palladium, rhodium and the like catalyze alkenyl amine or alkynyl amine to synthesize imine; (5) the complex formed by the transition metal cations catalyzes various oxime structures to generate amino-Heck reaction; (6) microwave radiation or photochemical methods.
In conclusion, the preparation method of the imine compound has the advantages of no danger in the experimental process, simple and feasible operation steps, easily available raw materials and considerable yield, and the method can be expanded to substrates containing different substituents and shows good substrate adaptability. Therefore, the method has potential use value.
It should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.
Claims (7)
1. A method for producing an imine compound, characterized by comprising: under the anhydrous and anaerobic condition, adding oxime ether and samarium or ytterbium metal into a reaction vessel in a one-pot manner, taking tetrahydrofuran as a solvent, initiating at high temperature by using an iodine simple substance, carrying out an inert gas protection reaction, reacting for 4 hours at 60 ℃, detecting the reaction progress by using a TLC plate, quenching the reaction by using water, extracting by using ethyl acetate, washing by using saturated salt water, drying by using anhydrous sodium sulfate, and carrying out column chromatography purification by using alkaline alumina to obtain a product
。
2. The method of claim 1, wherein: the molar ratio of the oxime ether to the metal simple substance is 1: 1.5.
3. The method of claim 1, wherein: the metal simple substance is as follows: tetrahydrofuran was 0.75 mmol: 5 ml.
4. The method of claim 1, wherein: the oxime ethers are: tetrahydrofuran was 0.5 mmol: 2 ml.
5. The method of claim 1, wherein: the high-temperature initiation temperature is 60 ℃, and the reaction time is 4 h.
6. The method of claim 1, wherein: the reaction was quenched with water, 2ml of water was used.
7. The method of claim 1, wherein: the alkaline alumina is 200-300 meshes.
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