CN117552025A - Metal-free 1, 4-enedione selective hydrogenation reduction method - Google Patents

Abstract

The invention discloses a metal-free 1, 4-enedione selective hydrogenation reduction method, which belongs to the technical field of organic synthesis. The method comprises the following steps: to the reactor was added 0.1mmol of substituted 1, 4-enedione, 0.2mmol of tetra-n-butyl ammonium perchlorate, and the catalyst was added to the reaction vessel in 1, 2-dichloroethane: hexafluoroisopropanol: after the electrocatalytic reaction in water= (4.5 ml:0.5ml:0.1 ml) was completed, the crude product was concentrated using a rotary evaporator, and then the target product was obtained by silica gel column chromatography separation. The metal-free 1, 4-enedione selective hydrogenation reduction method provided by the invention is scientific and reasonable, and the synthetic route is green and environment-friendly, and a metal catalyst is not needed; the reaction solvent is 1, 2-dichloroethane, hexafluoroisopropanol and water; the substrate can react under lower current; the synthesis method is simple and the reaction is rapid; the yield of the target compound is high, and the product is easy to purify. Which is a kind ofThe reaction equation is as follows:

Description

Metal-free 1, 4-enedione selective hydrogenation reduction method

Technical Field

The invention belongs to the technical field of organic synthesis, and particularly relates to a metal-free 1, 4-enedione selective hydrogenation reduction method.

Background

The reduction of unsaturated carbon-carbon bonds is one of the basic reactions in organic synthesis and industry, and the industrial application range of the unsaturated carbon-carbon bond can be from fine chemicals to drug synthesis, so that the unsaturated carbon-carbon bond has great significance; ((a) J.P.Collman, K.M.Kosydar, M.Bressan, W.Lamanna and T.Garrett, J.Am.Chem.Soc.,1984,106,2569-2579), (b) c.zheng and s. -L.You, chem.Soc.Rev.,2012,41,2498-2518, (c) d.wang and D.Astruc, chem.Rev.,2015,115,6621-6686.) 1, 4-dione moieties are present in a variety of natural products and bioactive compounds; (a) S. -H.Li, J.Wang, X. -M.Niu, Y. -H.shen, H. -J.Zhang, H. -D.Sun, M. -L.Li, Q. -E.Tian, Y.Lu, P.Cao, Q. -T.Zheng, org.Lett.,2004,6,4327-4330; b) G.Valot, C.S.Regens, D.P.O' Maley, E.Godineau, H.Takikawa, A.F urstner, angew.chem.,2013,125,9713-9717.) the 1, 4-dione compounds are versatile synthetic precursors of biologically active five-membered heterocycles (e.g., pyrrole, furan, thiophene, and cyclopentenone) with unique biological properties. (a) H.S.P.Rao, S.Jothilingam, J.Org.Chem.,2003,68,5392-5394; b) M.Biava, G.C.Porretta, D.Deidda, R.Pompei, A.Tafi, F.Manetti, bioorg.Med.Chem.,2004,12,1453-1458; c) J.B.Chaires, J.Ren, D.Hamelberg, A.Kumar, V.Pandya, D.W.Boykin, W.D.Wilson, J.Med.Chem.,2004,47,5729-5742.)

As an important heterocyclic ring synthesis intermediate, the quantitative method for providing the 1, 4-diketone is not much and complicated, and the development of a novel method for rapidly and efficiently selectively reducing the 1, 4-enedione has important practical significance.

The process for synthesizing 1, 4-diketones is reported by the university of south opening Wang Qingmin group: under photocatalysis, the visible light of alpha-chloroketone and ethyl enolacetate mediates the free radical coupling reaction to obtain the 1, 4-enedione compound. (adv. Synth. Catalyst., 2020,362,4391-4396.) equation (i):

the above method has obvious disadvantages of using metal catalyst, alkali, long reaction time, etc.

Disclosure of Invention

In order to overcome the defects of the existing synthesis of 1, 4-diketone compounds, the invention provides a metal-free selective hydrogenation reduction method for 1, 4-enedione.

Electrocatalytic synthesis reactions have a number of significant advantages: the catalyst which is poisonous or difficult to treat can be avoided, electrons are green reaction reagents, the purity of reaction products is high, the reaction products are easy to separate, and the environment is hardly polluted; in the electrocatalytic reaction, the reaction rate can be regulated and controlled by changing the electrode voltage or current so as to avoid side reactions, thereby improving the selectivity and the yield of the target product.

A metal-free 1, 4-enedione selective hydrogenation method is characterized in that 0.1mmol of substituted 1, 4-enedione and 0.2mmol of tetra-n-butyl ammonium perchlorate are added into a reactor, and a solvent is 1, 2-dichloroethane: hexafluoroisopropanol: water=4.5 ml:0.5ml:0.1ml, the current used is 5mA, the reaction temperature is 20 ℃, the reaction time is 2h, after the power-on promotion reaction is finished, the crude product is obtained by concentrating by using a rotary evaporator, and the chemical process is shown as a reaction formula II:

R ¹ the substituent groups are selected from hydrogen, fluorine, chlorine, tertiary butyl and methyl; r is R ² The substituent groups are selected from hydrogen, fluorine, chlorine and methyl.

The molar ratio of the substituted 1, 4-enedione to tetra-n-butyl ammonium perchlorate is 1:2, the solvent is 1, 2-dichloroethane: hexafluoroisopropanol: water=45: 5:1 (volume ratio).

The beneficial effects of the invention are as follows: the metal-free 1, 4-enedione selective hydrogenation reduction method provided by the invention is scientific and reasonable, provides a novel way for reducing 1, 4-enedione, and obtains the 1, 4-dione compound with various substituent groups by the method, and is characterized in that: the synthetic route is green and environment-friendly, and a metal catalyst is not needed; the reaction solvent is 1, 2-dichloroethane, hexafluoroisopropanol and water; the substrate can react under weak current; the synthesis method is simple and the reaction is rapid; the yield of the target compound is high, and the product is easy to purify.

Drawings

FIG. 1 is an NMR spectrum of compound 2b prepared in example 2;

FIG. 2 is an NMR spectrum of compound 2f prepared in example 6;

FIG. 3 is an NMR spectrum of compound 2i prepared in example 9.

Detailed Description

The invention is described in further detail below with reference to the attached drawings and specific examples:

the test methods described in the following examples, unless otherwise specified, are all conventional; the reagents and materials, unless otherwise specified, are commercially available.

Example 1

Preparation of 1, 4-enedione 2a

To a 10mL membrane-free electrolyzer were added 1, 4-enedione 1a (0.1 mmol,23.8 mg), tetra-n-butyl ammonium perchlorate (0.2 mmol,68.4 mg), and graphite felt electrodes (2cm x 1cm x 0.5cm) were used for both the negative and positive electrodes. 1, 2-dichloroethane is added: hexafluoroisopropanol: water= (4.5 ml:0.5ml:0.1 ml). The electrolysis was carried out at room temperature under a constant current of 5mA, and the reaction was carried out for 2 hours. After the reaction was completed, the solvent was removed by using a rotary evaporator to obtain a crude product, which was separated by column chromatography (200-300 mesh silica gel, petroleum ether/ethyl acetate=15/1), and the solvent was removed by using a rotary evaporator to obtain an unsubstituted 1, 4-dione 2a as a target product in a yield of 96%.

Spectrogram analysis data 2a:

¹ H NMR(500MHz,CDCl ₃ )δ8.04(d,J＝7.2Hz,4H),7.58(t,J＝7.0Hz,2H),7.48(t,J＝6.8Hz,4H),3.47(s,4H). ¹³ C NMR(125MHz,CDCl ₃ )δ198.8,136.9,133.3,128.7,128.3,32.7.

example 2

1b was used instead of 1a in example 1, and the other conditions were the same as in example 1, and the experimental results are shown in Table 1.

Spectrogram analysis data 2b:

¹ H NMR(500MHz,CDCl ₃ )δ8.04(d,J＝7.6Hz,2H),7.94(d,J＝8.0Hz,2H),7.57(t,J＝7.3Hz,1H),7.48(t,J＝7.7Hz,2H),7.27(d,J＝8.2Hz,2H),3.44(d,J＝2.2Hz,4H),2.42(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ198.8,198.3,143.9,136.8,134.3,133.1,129.3,128.6,128.2,128.1,32.6,32.5,21.6.

example 3

1c was used instead of 1a in example 1, and the other conditions were the same as in example 1, and the experimental results are shown in Table 1.

Spectrogram analysis data 2c:

¹ H NMR(500MHz,CDCl ₃ )δ8.04(d,J＝7.7Hz,2H),7.99(d,J＝8.4Hz,2H),7.57(t,J＝7.3Hz,1H),7.50–7.48(m,4H),3.46(s,4H),1.35(s,9H). ¹³ C NMR(125MHz,CDCl ₃ )δ198.8,198.4,156.9,136.8,134.2,133.1,128.6,128.1,128.1,125.5,35.1,32.7,32.5,31.1.

example 4

1d was used instead of 1a in example 1, and the other conditions were the same as in example 1, and the experimental results are shown in Table 1.

Spectrogram analysis data 2d:

¹ H NMR(500MHz,CDCl ₃ )δ8.10–8.01(m,4H),7.58(t,J＝7.1Hz,1H),7.48(t,J＝7.6Hz,2H),7.15(t,J＝8.5Hz,2H),3.44(dd,J＝14.7,6.2Hz,4H). ¹³ C NMR(125MHz,CDCl ₃ )δ198.6,197.1,166.8,164.8,136.7,133.3,133.2,133.2,130.8,130.7,128.6,128.1,115.8,115.6,32.6,32.4.

example 5

1e was used instead of 1a in example 1, and the other conditions were the same as in example 1, and the experimental results are shown in Table 1.

Spectrogram analysis data 2e:

¹ H NMR(500MHz,CDCl ₃ )δ8.03(d,J＝7.7Hz,2H),7.97(d,J＝7.6Hz,2H),7.57(d,J＝7.2Hz,1H),7.51–7.42(m,4H),3.45(d,J＝4.3Hz,2H),3.42(d,J＝5.8Hz,2H). ¹³ C NMR(125MHz,CDCl ₃ )δ198.5,197.5,139.6,136.7,135.1,133.2,129.6,128.9,128.6,128.1,32.6,32.5.

example 6

1f was used instead of 1a in example 1, and the other conditions were the same as in example 1, and the experimental results are shown in Table 1.

Spectrogram analysis data 2f:

¹ H NMR(500MHz,CDCl ₃ )δ7.97(d,J＝8.0Hz,4H),7.30(d,J＝8.1Hz,4H),3.46(s,4H),2.45(s,6H). ¹³ C NMR(125MHz,CDCl ₃ )δ198.5,143.9,134.3,129.3,128.3,32.5,21.7.

example 7

1g was used instead of 1a in example 1, and the other conditions were the same as in example 1, and the experimental results are shown in Table 1.

Spectrogram analysis data 2g:

¹ H NMR(500MHz,CDCl3)δ8.13–8.06(m,2H),7.96(d,J＝8.0Hz,2H),7.30(d,J＝8.0Hz,2H),7.17(t,J＝8.6Hz,2H),3.46–3.44(m,4H),2.44(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ196.2,195.2,164.8,162.8,142.0,132.3,131.3(d,J＝3.1Hz),128.8,128.7,127.3,126.2,113.7,113.6,30.5,19.6.

example 8

1h was used instead of 1a in example 1, the other conditions were the same as in example 1, and the experimental results are shown in Table 1.

Spectrogram analysis data 2h:

¹ H NMR(500MHz,CDCl ₃ )δ7.98(d,J＝8.5Hz,2H),7.93(d,J＝8.2Hz,2H),7.45(d,J＝8.6Hz,2H),7.27(d,J＝8.1Hz,2H),3.47–3.37(m,4H),2.42(s,3H). ¹³ C NMR(125MHz,CDCl ₃ )δ197.1,196.6,143.0,138.5,134.1,133.2,128.5,128.3,127.9,127.2,31.5,31.4,20.6.

example 9

1i was used instead of 1a in example 1, and the other conditions were the same as in example 1, and the experimental results are shown in Table 1.

Spectrogram analysis data 2i:

¹ H NMR(500MHz,CDCl ₃ )δ8.07–8.05(m,4H),7.15(t,J＝8.5Hz,4H),3.42(s,4H). ¹³ C NMR(125MHz,CDCl ₃ )δ197.0,166.9,164.8,133.2,130.8,130.7,115.8,115.6,32.4.

example 10

1j was used instead of 1a in example 1, and the other conditions were the same as in example 1, and the experimental results are shown in Table 1.

Spectral analysis data 2j:

¹ H NMR(500MHz,CDCl ₃ )δ7.97(d,J＝8.6Hz,4H),7.45(d,J＝8.6Hz,4H),3.42(s,4H). ¹³ C NMR(125MHz,CDCl ₃ )δ197.3,139.7,135.0,129.5,129.0,32.5.

TABLE 1

Claims (2)

1. A metal-free 1, 4-enedione selective hydrogenation method is characterized in that 0.1mmol of substituted 1, 4-enedione and 0.2mmol of tetra-n-butyl ammonium perchlorate are added into a reactor, and a solvent is 1, 2-dichloroethane: hexafluoroisopropanol: water=4.5 ml:0.5ml:0.1ml, the current used is 5mA, the reaction temperature is 20 ℃, the reaction time is 2h, after the power-on promotion reaction is finished, the crude product is obtained by concentrating by using a rotary evaporator, and the chemical process is shown as the reaction formula:

R ¹ the substituent groups are selected from hydrogen, fluorine, chlorine, tertiary butyl and methyl; r is R ² The substituent groups are selected from hydrogen, fluorine, chlorine and methyl.

2. The method of manufacturing according to claim 1, wherein: the electrode material is graphite felt.