CN108341733B - Novel electronic salt system and reduction method of unsaturated hydrocarbon compound - Google Patents

Novel electronic salt system and reduction method of unsaturated hydrocarbon compound Download PDF

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CN108341733B
CN108341733B CN201710059952.4A CN201710059952A CN108341733B CN 108341733 B CN108341733 B CN 108341733B CN 201710059952 A CN201710059952 A CN 201710059952A CN 108341733 B CN108341733 B CN 108341733B
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unsaturated hydrocarbon
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alkali metal
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安杰
张小河
雷鹏
凌云
李恒朝
吴羽飞
丁宇轩
阿迪拉
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China Agricultural University
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Abstract

The invention discloses an electronic salt system and a method for reducing unsaturated hydrocarbon compounds by utilizing the electronic salt system, belongs to the field of organic synthesis, and solves the problems that the reduction method of unsaturated hydrocarbon compounds in the prior art is complex in operation, harsh in conditions, easy to generate complex over-reduction products and the like. The electronic salt can be synthesized by the following reagents: alkali metal reagent, ether and alcohol, wherein the ether is crown ether or crypt ether; the reduction method adopts the electronic salt system, and the unsaturated hydrocarbon compound and the electronic salt system are subjected to a reduction reaction in an organic solvent. The method for reducing the unsaturated hydrocarbon compound is used for reducing the unsaturated hydrocarbon compound.

Description

Novel electronic salt system and reduction method of unsaturated hydrocarbon compound
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a novel electronic salt system and a reduction method of an unsaturated hydrocarbon compound.
Background
At present, the reduction method of unsaturated hydrocarbon compounds (such as aromatic compounds, alkenes and alkynes) mainly comprises the following steps: birch reduction, reductive silylation, photochemical electron transfer, catalytic hydrogenation, electrochemical reduction, and the like. However, the method has complex operation, harsh conditions, difficult control of the generated product and limited application range.
The birch reduction reaction, one of the most important reduction methods for unsaturated hydrocarbon compounds, is widely used for reduction of aromatic compounds, and is known as a "bridge" between an aromatic compound and an alicyclic compound (and some aliphatic chain compounds).
In 2002, Donohoe et al used LiDBB as a reducing agent to achieve several reduction reactions of heteroaromatic compounds which are not easily performed under conventional Burger reaction conditions (J.Org.chem.2002,67(14),5015-5018. however, this system has a weak reducing ability, limiting its applicability.
There is also an improved birch reduction reaction in the prior art, which is called as Benkeser reduction reaction, and the Benkeser reduction reaction can use amine compounds with low boiling point as complexing agents instead of liquid ammonia to realize the reduction reaction of aromatic compounds (compr.org.synth.second ed.2014,8, 639-. However, this system is more reducing than the conventional birch system and often produces over-reduced by-products or completely converts reactants to more highly saturated products.
Disclosure of Invention
The invention aims to provide an electronic salt system and a reduction method of an unsaturated hydrocarbon compound, and solves the problems that the reduction method of the unsaturated hydrocarbon compound in the prior art is complex in operation, harsh in conditions and difficult in control of generated products.
In order to achieve the purpose, the technical scheme of the invention is as follows:
establishing a novel electronic salt system, wherein the electronic salt system comprises an alkali metal reagent, ethers and alcohols, and the ethers are crown ethers or cryptates; the electron salt system comprises the following components in molar ratio: 2-15 alkali metals, 2-10 ethers and 2-10 alcohols in the alkali metal reagent.
The alkali metal reagent is alkali metal block or alkali metal dispersion in dispersant or Na-SG (I); the alkali metal is sodium, potassium or lithium; the particle size of the alkali metal in the alkali metal dispersion is 5-100 μm; the dispersant is mineral oil, paraffin or toluene. The ether is one or more of 18-crown-6, 15-crown-5, 12-crown 4, dibenzo-18-crown-6 and [2.2.2] cryptate mixed at any proportion. The alcohol is one or a mixture of more of MeOH, EtOH, n-PrOH, i-PrOH, n-BuOH and t-BuOH in any proportion.
The reduction method of the unsaturated hydrocarbon compound adopts the electron salt system, and the unsaturated hydrocarbon compound and the electron salt system are subjected to reduction reaction in an organic solvent.
The unsaturated hydrocarbon compound is a substituted aromatic compound, the substituted aromatic compound and an electronic salt system react in an organic solvent to generate a substituted cyclic olefin or alicyclic compound, and the reaction general formula is as follows:
Figure BDA0001218589760000021
alternatively, the first and second electrodes may be,
Figure BDA0001218589760000022
alternatively, the first and second electrodes may be,
Figure BDA0001218589760000031
wherein, R1 represents one of hydrogen, linear or branched alkyl, substituted or unsubstituted cycloalkyl, linear or branched alkenyl and substituted alkenyl; n is zero or a positive integer.
The unsaturated hydrocarbon compound is an aromatic heterocyclic compound, the aromatic heterocyclic compound and an electron salt system react in an organic solvent to generate a substituted heterocyclic compound, and the reaction general formula is as follows:
Figure BDA0001218589760000032
alternatively, the first and second electrodes may be,
Figure BDA0001218589760000033
alternatively, the first and second electrodes may be,
Figure BDA0001218589760000034
wherein, R2 represents one of linear or branched alkyl, substituted or unsubstituted cycloalkyl, linear or branched alkenyl and substituted alkenyl; x represents an oxygen atom or a nitrogen atom, the number of oxygen atoms or nitrogen atoms in the heterocycle being equal to or greater than one; n is zero or a positive integer.
The unsaturated hydrocarbon compound is alkyne or alkene, the alkyne or alkene reacts with the electron salt system in an organic solvent to generate an alkane compound, and the reaction general formula is as follows:
Figure BDA0001218589760000035
alternatively, the first and second electrodes may be,
Figure BDA0001218589760000036
wherein, R3 represents one of aryl, linear or branched alkyl, substituted or unsubstituted cycloalkyl, linear or branched alkenyl and substituted alkenyl; r4 represents one of aryl, linear or branched alkyl, substituted or unsubstituted cycloalkyl, linear or branched alkenyl and substituted alkenyl.
The reduction method comprises the following steps:
step S1: under the protection of nitrogen, mixing and stirring an alkali metal reagent, ethers and an organic solvent uniformly;
step S2: stirring and mixing unsaturated hydrocarbon compounds and alcohols uniformly, adding an organic solvent into a mixed solution of the unsaturated hydrocarbon compounds and the alcohols, and stirring and mixing uniformly to obtain a substrate solution;
step S3: mixing the substrate solution prepared in the step S2 with the alkali metal reagent and ether mixed solution prepared in the step S1 for reaction, and quenching the reaction to obtain a product to be treated;
step S4: extracting, drying the organic phase, concentrating and separating the product to be treated to obtain the reduction product of the unsaturated hydrocarbon compound.
The organic solvent is one or a mixture of several of n-pentane, hexane, cyclohexane, diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran and dioxane in any proportion.
The reaction temperature of the reduction reaction is-30 ℃ to 30 ℃; the reaction time is 0.1-60 min.
The molar ratio of the unsaturated hydrocarbon compound to the alkali metal in the alkali metal reagent is 1: 2-15; the molar ratio of the unsaturated hydrocarbon compound to the ethers is 1: 2-10; the molar ratio of the unsaturated hydrocarbon compound to the alcohol is 1: 2 to 10.
The invention has the beneficial effects that:
1) the invention provides a method for reducing unsaturated hydrocarbon compounds, which adopts an electronic salt system consisting of different alkali metals, ethers and alcohol compounds to replace the alkali metal/liquid ammonia electronic salt system used in the traditional birch reduction. And the new improved birch reaction has higher chemoselectivity compared with the traditional birch reduction reaction.
2) The reduction method of the unsaturated hydrocarbon compound provided by the invention has the advantages of high yield, safe and simple operation, easily obtained raw materials, no use of low boiling point solvents such as liquid ammonia and the like in the preparation process, no use of transition metal reagents such as samarium diiodide and the like, less by-products and lower toxicity.
3) Compared with the traditional reduction method of aromatic compounds by the birch reduction reaction, the reduction method of aromatic compounds provided by the invention greatly improves the chemical selectivity of the reaction, and can even reduce benzene rings under the condition of being compatible with non-benzyl substituted amide groups.
Detailed Description
The following examples are given to further illustrate the embodiments of the present invention.
The invention provides a novel electronic salt system, which comprises an alkali metal reagent, ethers and alcohols, wherein the ethers are crown ethers or crypt ethers, and the molar ratio of the components of the electronic salt system is calculated as follows: 2-15 alkali metals, 2-10 ethers and 2-10 alcohols in the alkali metal reagent, preferably alkali metals in the alkali metals: ethers: alcohols are 1: 1: 1.
wherein the alkali metal reagent is alkali metal block or alkali metal dispersion in dispersant or Na-SG (I); alkali metal means especially sodium, potassium or lithium, preferably sodium; dispersants mean in particular mineral oils, paraffins or toluene, preferably mineral oils; the particle size of the alkali metal in the alkali metal dispersion is 5 to 100. mu.m, preferably 5 to 10 μm.
The ethers are one or more of 18-crown-6, 15-crown-5, 12-crown 4, dibenzo-18-crown-6 and [2.2.2] cryptate, preferably 15-crown-5.
The alcohol is one or more of MeOH, EtOH, n-PrOH, i-PrOH, n-BuOH and t-BuOH mixed at any proportion, preferably i-PrOH.
The invention also provides a method for reducing unsaturated hydrocarbon compounds, belonging to the improved birch reduction reaction. The method adopts the electron salt system, and the unsaturated hydrocarbon compound and the electron salt system are subjected to reduction reaction in an organic solvent.
Specifically, the unsaturated hydrocarbon compound may be a substituted aromatic compound, and the substituted aromatic compound reacts with an electron salt system in an organic solvent to form a substituted cyclic olefin or alicyclic compound, wherein the reaction formula is as follows:
Figure BDA0001218589760000051
alternatively, the first and second electrodes may be,
Figure BDA0001218589760000052
alternatively, the first and second electrodes may be,
Figure BDA0001218589760000061
wherein, R1 represents one of hydrogen, linear or branched alkyl, substituted or unsubstituted cycloalkyl, linear or branched alkenyl and substituted alkenyl; n is zero or a positive integer.
Or, the unsaturated hydrocarbon compound can also be an aromatic heterocyclic compound, the aromatic heterocyclic compound and the electron salt system react in an organic solvent to generate a substituted heterocyclic compound, and the reaction general formula is as follows:
Figure BDA0001218589760000062
alternatively, the first and second electrodes may be,
Figure BDA0001218589760000063
alternatively, the first and second electrodes may be,
Figure BDA0001218589760000064
wherein, R2 represents one of linear or branched alkyl, substituted or unsubstituted cycloalkyl, linear or branched alkenyl and substituted alkenyl; x represents an oxygen atom or a nitrogen atom, the number of oxygen atoms or nitrogen atoms in the heterocycle being equal to or greater than one; n is zero or a positive integer.
Or, the unsaturated hydrocarbon compound may also be alkyne or alkene, and the alkyne or alkene reacts with the electron salt system in an organic solvent to generate the alkane compound, wherein the reaction formula is as follows:
Figure BDA0001218589760000065
alternatively, the first and second electrodes may be,
Figure BDA0001218589760000066
wherein R3 represents an aromatic group, a linear or branched alkyl group, a substituted alkyl group, or a substituted alkyl groupOne of substituted or unsubstituted cycloalkyl, linear or branched alkenyl and substituted alkenyl; r4Represents one of aryl, straight-chain or branched-chain alkyl, substituted or unsubstituted cycloalkyl, straight-chain or branched-chain alkenyl and substituted alkenyl; r3 and R4 may be the same or different.
The method for reducing the unsaturated hydrocarbon compound provided by the invention comprises the following specific steps:
step S1: under the protection of nitrogen, mixing and stirring an alkali metal reagent, ethers and an organic solvent uniformly;
step S2: stirring and mixing unsaturated hydrocarbon compounds and alcohols uniformly, adding an organic solvent into a mixed solution of the unsaturated hydrocarbon compounds and the alcohols, and stirring and mixing uniformly to obtain a substrate solution;
step S3: mixing the substrate solution prepared in the step S2 with the alkali metal reagent and ether mixed solution prepared in the step S1 for reaction, and quenching the reaction to obtain a product to be treated;
step S4: extracting, drying the organic phase, concentrating and separating the product to be treated to obtain the reduction product of the unsaturated hydrocarbon compound.
In the above-mentioned method for reducing an unsaturated hydrocarbon compound, the organic solvent is one or more selected from n-pentane, hexane, cyclohexane, diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran and dioxane, preferably tetrahydrofuran.
The reaction temperature is-30 ℃ to 30 ℃, and 0 ℃ is preferred; the reaction time is 0.1-60 min, preferably 5 min.
The molar ratio of the unsaturated hydrocarbon compound to the alkali metal in the alkali metal reagent is 1: (2-15), preferably 1: 6.
the molar ratio of the unsaturated hydrocarbon compound to the ether is 1: (2-10), preferably 1: 6.
the molar ratio of the unsaturated hydrocarbon compound to the alcohol is 1: (2-10), preferably 1: 6.
example 1
Figure BDA0001218589760000071
In a 10ml single-neck flask, under nitrogen, 172.5mg (3.0mmol) of sodium reagent (40 wt%, suspension in toluene, particle size <100 μm), 15-crown-5593.7 μ l (3.0mmol), 1ml of tetrahydrofuran were added and stirred at 0 ℃ for 5 min.
A1.5 ml centrifuge tube was taken, added with 89.1mg (0.5mmol) of diphenylacetylene, 229.3. mu.l (3.0mmol) of isopropanol and 1ml of tetrahydrofuran, shaken well, taken into a syringe, washed with 1ml of tetrahydrofuran and taken into the syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 66.5mg of a target compound with the yield of 73 percent.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ7.38-7.23(m,4H),7.23-7.13(m,6H),2.92(s,4H)。
example 2
Figure BDA0001218589760000081
In a 10ml single-neck flask, under nitrogen, 172.5mg (3.0mmol) of sodium reagent (40 wt%, suspension in toluene, particle size <10 μm), 15-crown-5593.7 μ l (3.0mmol), 1ml of 2-methyltetrahydrofuran were added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, and 64.6mg (0.5mmol) of quinoline, 229.3. mu.l (3.0mmol) of isopropanol, and 1ml of 2-methyltetrahydrofuran were added thereto, shaken well, taken into a syringe, washed with 1ml of 2-methyltetrahydrofuran, and taken into a syringe. Adding the prepared mixed solution into a single-mouth bottle, and stirring for 15min at 0 ℃.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying the organic phase, concentrating, and separating by column chromatography to obtain 40.6mg of target compound with the yield of 70%.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ7.01(t,J＝7.7Hz,2H),6.65(t,J＝7.4Hz,1H),6.51(d,J＝7.7Hz,1H),3.41-3.24(m,2H),2.81(t,J＝6.4Hz,2H),2.05-1.91(m,2H)。
example 3
Figure BDA0001218589760000091
In a 10ml single-neck flask, under nitrogen protection, 172.5mg (3.0mmol) of sodium reagent (40 wt%, sodium dispersion in paraffin wax, particle size <10 μm), 18-crown-6674.8 μ l (3.0mmol), 1ml dioxane were added and stirred at 0 ℃ for 20 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, 76.1mg (0.50mmol) of acenaphthylene, 229.3. mu.l (3.0mmol) of methanol and 1ml of dioxane were added, shaken well, taken into a syringe, washed with 1ml of dioxane and taken into the syringe. Adding the prepared mixed solution into a single-mouth bottle, and stirring for 45min at 0 ℃.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 57.8mg of a target compound with the yield of 75%.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ7.58(d,J＝8.1Hz,2H),7.43(t,J＝7.5Hz,2H),7.32-7.21(m,2H),3.40(s,4H)。
example 4
Figure BDA0001218589760000092
In a 10ml single neck flask, under nitrogen, 195.5mg (1.5mmol) of potassium reagent (30 wt%, potassium dispersion in mineral oil, particle size <100 μm), 12-crown-4242.7 μ l (1.5mmol), 1ml of ether were added and stirred for 5min at-30 ℃.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, added with 89.1mg (0.50mmol) of anthracene, 67.6. mu.l (1.5mmol) of ethanol, and 1ml of diethyl ether, shaken up, taken into a syringe, washed with 1ml of diethyl ether, and taken into the syringe. The prepared mixed solution is added into a single-mouth bottle and stirred for 5min at the temperature of minus 30 ℃.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 60.4mg of a target compound with the yield of 60%.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ7.29(dt,J＝7.3,3.6Hz,4H),7.24-7.12(m,4H),3.94(s,4H)。
example 5
Figure BDA0001218589760000101
In a 10ml single-neck flask, under nitrogen, 20.8mg (3.0mmol) of lithium reagent (lithium sand, particle size <100 μm), dibenzo-18-crown-6772.3 μ l (3.0mmol), 1ml of n-pentane were added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was charged with 89.6mg (0.5mmol) of acridine, 224.2. mu.l (3.0mmol) of n-propanol and 1ml of n-pentane, shaken well, taken into a syringe, washed with 1ml of n-pentane and taken into the syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5min
The reaction was quenched with 2ml of saturated aqueous NaHCO3 solution and warmed to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 68.0mg of a target compound with the yield of 75%.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ7.08(t,J＝8.4Hz,4H),6.85(t,J＝7.4Hz,2H),6.66(d,J＝7.8Hz,2H),5.94(s,1H),4.05(s,2H)。
example 6
Figure BDA0001218589760000102
In a 10ml single neck flask, under nitrogen, 258.8mg (4.5mmol) of sodium reagent (40 wt%, sodium dispersion in mineral oil, particle size <10 μm), [2.2.2] cryptate 1757.5 μ l (4.5mmol), 1ml of hexane were added and stirred at 30 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was charged with 86.3mg (0.5mmol) of p-tert-butyl anisole, 343.9. mu.l (4.5mmol) of isopropanol, and 1ml of hexane, shaken, taken into a syringe, washed with 1ml of hexane, and taken into a syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 30 ℃ for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 58.1mg of a target compound with the yield of 60%.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ5.47(dd,J＝4.2,2.7Hz,1H),4.65(t,J＝3.4Hz,1H),3.55(s,3H),2.90-2.79(m,2H),2.74(ddd,J＝8.8,6.2,2.9Hz,2H),1.06(s,9H)。
example 7
Figure BDA0001218589760000111
In a 10ml single neck flask, under nitrogen, 115.0mg (2.0mmol) of sodium reagent (40 wt%, sodium dispersion in mineral oil, particle size <10 μm), 15-crown-5395.8 μ l (2.0mmol), 1ml tetrahydrofuran are added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube is taken, added with 89.1mg (0.5mmol) of phenanthrene, 152.9 mu l (2.0mmol) of isopropanol and 1ml of tetrahydrofuran, shaken up, taken into a syringe, washed by 1ml of tetrahydrofuran and taken into the syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 67.6mg of a target compound with the yield of 75%.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ7.82(d,J＝7.9Hz,2H)，7.41-7.32(m,2H)，7.28(dd,J＝9.4,6.9Hz,4H)，2.94(s,4H)。
example 8
Figure BDA0001218589760000121
In a 10ml single neck flask, under nitrogen, 172.5mg (3.0mmol) of sodium reagent (40 wt%, sodium dispersion in mineral oil, particle size <10 μm), 15-crown-5593.7 μ l (3.0mmol), 1ml of tetrahydrofuran are added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, and 64.6mg (0.5mmol) of isoquinoline, 229.3. mu.l (3.0mmol) of isopropanol and 1ml of tetrahydrofuran were added thereto, shaken well, taken into a syringe, washed with 1ml of tetrahydrofuran and taken into the syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying the organic phase, concentrating, and separating by column chromatography to obtain 34.4mg of target compound with the yield of 52%.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ7.16-7.02(m,3H),6.96(dd,J＝8.4,4.4Hz,1H),3.97(s,2H)，3.09(t,J＝6.0Hz,2H),2.75(t,J＝6.0Hz,2H)。
example 9
Figure BDA0001218589760000122
In a 10ml single-neck flask, under nitrogen protection, Na-SG (I) (35 wt%, sodium dispersion in mineral oil, particle size <10 μm), 15-crown-5197.9 μ l (1.0mmol), 1ml cyclohexane were added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, 101.5mg (0.5mmol) of 3-phenyl-1- (pyrrolidin-1-yl) propan-1-one, 74.8. mu.l (1.0mmol) of isopropanol, and 1ml of cyclohexane were added, shaken well, taken in a syringe, washed with 1ml of cyclohexane, and taken in a syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 76.9mg of a target compound with the yield of 75%.
This example enables the reduction of the benzene ring under compatible amide group conditions with non-benzylic substitution.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ5.71(s,2H),5.46(s,1H),3.51-3.37(m,4H),2.80-2.52(m,4H),2.44-2.26(m,4H),1.90(ddd,J＝19.3,13.2,6.6Hz,4H)。
example 10
Figure BDA0001218589760000131
In a 10ml single neck flask, under nitrogen, 115.0mg (2.0mmol) of sodium reagent (40 wt%, suspension in toluene, particle size <10 μm), 15-crown-5593.7 μ l (3.0mmol), 1ml of tetrahydrofuran were added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was charged with 121.7mg (0.5mmol) of (1-phenylcyclopentyl) (pyrrolidin-1-yl) methanone, 382.2. mu.l (5.0mmol) of isopropanol, and 1ml of tetrahydrofuran, shaken well, taken into a syringe, washed with 1ml of tetrahydrofuran, and taken into a syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 97.8mg of a target compound with the yield of 80%.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ5.81-5.60(m,2H),5.59-5.46(m,1H),3.42(dt,J＝30.6,6.3Hz,5H),2.85-2.65(m,2H),2.62-2.46(m,2H),2.25-1.99(m,4H),1.93-1.71(m,10H),1.70-1.45(m,7H)。
example 11
Figure BDA0001218589760000141
In a 10ml single neck flask, under nitrogen, 431.2mg (7.5mmol) of sodium reagent (40 wt%, sodium dispersion in mineral oil, particle size <10 μm), 15-crown-5593.7 μ l (3.0mmol), 1ml of tetrahydrofuran were added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, 158.3mg (0.5mmol) of heptadecylbenzene, 229.3. mu.l (3.0mmol) of isopropanol, and 1ml of tetrahydrofuran were added, shaken well, taken into a syringe, washed with 1ml of tetrahydrofuran, and taken into the syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 111.5mg of a target compound with the yield of 70%.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ5.80-5.60(m,2H),5.41(s,1H),2.67(d,J＝6.9Hz,2H),2.61-2.53(m,2H),1.36(d,J＝22.2Hz,3H),1.25(s,32H)。
example 12
Figure BDA0001218589760000142
In a 10ml single neck flask, under nitrogen, 172.5mg (3.0mmol) of sodium reagent (40 wt%, sodium dispersion in mineral oil, particle size <10 μm), 15-crown-5989.5 μ l (5.0mmol), 1ml of tetrahydrofuran are added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, and 64.1mg (0.5mmol) of naphthalene, 229.3. mu.l (3.0mmol) of isopropanol and 1ml of tetrahydrofuran were added thereto, shaken well, taken into a syringe, washed with 1ml of tetrahydrofuran and taken into the syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated salt solution for extraction, drying the organic phase,Concentration and column chromatography separation to obtain 49.6mg of the target compound with 73% yield.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ5.78(s,4H),2.59(s,8H),7.18-7.01(m,4H),2.95-2.72(m,4H),1.91-1.77(m,4H)。
example 13
Figure BDA0001218589760000151
In a 10ml single neck flask, under nitrogen, 258.8mg (4.5mmol) of sodium reagent (40 wt%, sodium dispersion in mineral oil, particle size <10 μm), 15-crown-5890.6 μ l (4.5mmol), 1ml of tetrahydrofuran are added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, and 58.1mg (0.5mmol) of indene, 343.9. mu.l (4.5mmol) of isopropanol and 1ml of tetrahydrofuran were added, shaken well, taken into a syringe, washed with 1ml of tetrahydrofuran and taken into the syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 43.7mg of a target compound with the yield of 74 percent.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ6.76(d,J＝132.8Hz,2H),2.58(s,4H),2.32(s,4H)。
example 14
Figure BDA0001218589760000161
In a 10ml single neck flask, under nitrogen, 115.0mg (2.0mmol) of sodium reagent (40 wt%, sodium dispersion in mineral oil, particle size <10 μm), 15-crown-5395.8 μ l (2.0mmol), 1ml tetrahydrofuran are added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, and 59.1mg (0.5mmol) of 2, 3-benzofuran (152.9. mu.l (2.0mmol) of isopropanol and 1ml of tetrahydrofuran were added thereto, shaken well, taken into a syringe, washed with 1ml of tetrahydrofuran and taken into the syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 45mg of a target compound with the yield of 75%.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ7.30-6.97(m,2H),6.97-6.60(m,2H),4.55(t,J＝8.7Hz,2H),3.19(t,J＝8.7Hz,2H)。
1H NMR(500MHz,CDCl3)δ7.13(dd,J＝7.5Hz,1.2Hz,1H),δ7.06(td,J＝7.7Hz,1.6Hz,1H),6.88(td,J＝7.5Hz,0.9Hz,1H),6.73(dd,J＝8.0Hz,0.9Hz,1H),5.16(s,1H),2.62(q,J＝7.6Hz,2H),1.24(t,J＝7.6Hz,1H)。
example 15
Figure BDA0001218589760000162
In a 10ml single neck flask, under nitrogen protection, 103.6mg (1.8mmol) of sodium reagent (40 wt%, sodium dispersion in mineral oil, particle size <10 μm), 15-crown-5356.2 μ l (1.8mmol), 1ml of tetrahydrofuran are added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, and 45.3mg (0.2mmol) of 9-chloromethylanthracene, 137.6. mu.l (1.8mmol) of isopropanol and 1ml of tetrahydrofuran were added, shaken well, taken into a syringe, washed with 1ml of tetrahydrofuran and taken into the syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 27.4mg of a target compound with the yield of 60%.
Structure confirmation data:
1HNMR(500MHz,CDCl3)δ7.45-7.21(m,8H),4.29-4.10(m,2H),4.01(m,1H),1.54(d,3H)。
example 16
Figure BDA0001218589760000171
In a 10ml single neck flask, under nitrogen, 86.3mg (1.5mmol) of sodium reagent (40 wt%, sodium dispersion in mineral oil, particle size <10 μm), 15-crown-5296.9 μ l (1.5mmol), 1ml of tetrahydrofuran are added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, and 65.6mg (0.5mmol) of 1-methylindole, 114.7. mu.l (1.5mmol) of isopropanol and 1ml of tetrahydrofuran were added, shaken well, taken into a syringe, washed with 1ml of tetrahydrofuran and taken into the syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 47.9mg of a target compound with the yield of 72 percent.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ7.19-6.99(m,2H),6.69(t,J＝7.0Hz,1H),6.50(dd,J＝7.6,4.1Hz,1H),3.30(t,J＝8.1Hz,2H),2.96(t,J＝8.1Hz,2H),2.77(s,3H)。
example 17
Figure BDA0001218589760000181
In a 10ml single neck flask, under nitrogen, 86.3mg (1.0mmol) of sodium reagent (40 wt%, sodium dispersion in mineral oil, particle size <10 μm), 15-crown-5296.9 μ l (1.0mmol), 1ml of tetrahydrofuran are added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, and 90.1mg (0.5mmol) of trans-1, 2-stilbene, 114.7. mu.l (1.0mmol) of isopropanol and 1ml of tetrahydrofuran were added, shaken well, taken into a syringe, washed with 1ml of tetrahydrofuran and taken into the syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 65.6mg of a target compound with the yield of 72 percent.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ7.38-7.23(m,4H),7.23-7.13(m,6H),2.92(s,4H)。
example 18
Figure BDA0001218589760000182
In a 10ml single neck flask, under nitrogen, 172.5mg (3.0mmol) of sodium reagent (40 wt%, sodium dispersion in mineral oil, particle size <10 μm), 15-crown-5593.7 μ l (3.0mmol), 1ml of tetrahydrofuran are added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, and 69.1mg (0.5mmol) of 4-methoxybenzyl alcohol, 229.3. mu.l (3.0mmol) of isopropyl alcohol, and 1ml of tetrahydrofuran were added, shaken well, taken into a syringe, washed with 1ml of tetrahydrofuran, and taken into the syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying the organic phase, concentrating, and separating by column chromatography to obtain 49.1mg of the target compound with the yield of 70%.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ5.61(m,1H),4.65(m,1H),4.03(m,2H),3.58(s,3H),2.81(m,2H),2.68(m,2H)。
example 19
Figure BDA0001218589760000191
In a 10ml single neck flask, under nitrogen, 172.5mg (3.0mmol) of sodium reagent (40 wt%, sodium dispersion in mineral oil, particle size <10 μm), 15-crown-5593.7 μ l (3.0mmol), 1ml of tetrahydrofuran are added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, 116.7mg (0.5mmol) of N, N-a-trimethyl-4- (2-methylpropyl) -phenylacetamide, 229.3. mu.l (3.0mmol) of isopropanol, and 1ml of tetrahydrofuran were added, shaken well, taken into a syringe, washed with 1ml of tetrahydrofuran, and taken into a syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 66.9mg of a target compound with the yield of 73 percent.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ5.52(s,1H)，5.39(s,1H)，3.35-3.16(m,1H)，3.02-2.94(m,6H)，2.69-2.51(m,4H)，1.84(t,2H)，1.75-1.70(m,1H)，0.85(d,J＝6.3Hz,9H)。
example 20
Figure BDA0001218589760000201
In a 10ml single neck flask, under nitrogen, 172.5mg (3.0mmol) of sodium reagent (40 wt%, sodium dispersion in mineral oil, particle size <10 μm), 15-crown-5593.7 μ l (3.0mmol), 1ml of tetrahydrofuran are added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, and 75.6mg (0.5mmol) of 1-ethyl-4- (nitromethyl) benzene, 229.3. mu.l (3.0mmol) of isopropanol, and 1ml of tetrahydrofuran were added thereto, shaken well, taken in a syringe, washed with 1ml of tetrahydrofuran, and taken in a syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, drying and concentrating an organic phase, and separating by column chromatography to obtain 60.3mg of a target compound with the yield of 73 percent.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ6.99(d,J＝8.3Hz,2H),6.71-6.51(m,2H),3.58(s,2H),2.54(q,J＝7.6Hz,2H),1.19(t,3H)。
example 21
Figure BDA0001218589760000202
In a 25ml single neck flask, under nitrogen, 345.0mg (6.0mmol) of sodium reagent (40 wt%, sodium dispersion in mineral oil, particle size <10 μm), 15-crown-51187.5 μ l (6.0mmol), 2ml of tetrahydrofuran are added and stirred at 0 ℃ for 5 min.
Preparing a substrate solution. A1.5 ml centrifuge tube was taken, and 143.2mg (1.0mmol) of 4-methylquinoline, 458.5. mu.l (6.0mmol) of isopropanol, and 1ml of tetrahydrofuran were added thereto, shaken well, taken into a syringe, washed with 1ml of tetrahydrofuran, and taken into a syringe. Adding the mixed solution into a single-mouth bottle, and stirring at 0 deg.C for 5 min.
With 2ml of saturated NaHCO3The aqueous solution was quenched and allowed to warm to room temperature. Adding ether and saturated saline solution for extraction, washing organic phase with saturated NaCl water solution for 3 times, adding hydrochloric acid for acidification, separating water phase, adding saturated NaOH water solution for neutralization, extracting with ether, drying, and concentrating to obtain 103.0mg target compound with yield of 70%.
Structure confirmation data:
1H NMR(500MHz,CDCl3)δ7.04(d,J＝7.5Hz,1H),6.95(t,J＝7.6Hz,1H),6.62(t,J＝7.3Hz,1H),6.55–6.38(m,1H),3.75(d,J＝39.3Hz,1H),3.41–3.11(m,2H),2.99–2.81(m,1H),1.97(ddd,J＝13.0,9.0,4.6Hz,1H),1.66(dtd,J＝10.0,6.3,3.7Hz,1H),1.28(d,J＝7.0Hz,3H)。

Claims (8)

1. an electron salt system for use in the reduction of unsaturated hydrocarbon compounds, characterized in that:
the electronic salt system comprises an alkali metal reagent, ethers and alcohols, wherein the alkali metal reagent is a dispersion of alkali metal in a dispersing agent; alkali metal refers to sodium, potassium or lithium;
the ethers are one or more of 18-crown-6, 15-crown-5, 12-crown-4, dibenzo-18-crown-6 and [2.2.2] cryptate mixed at any proportion;
the alcohol is one or more of MeOH, EtOH, n-PrOH, i-PrOH, n-BuOH and t-BuOH mixed in any proportion;
the dispersant is mineral oil, paraffin or toluene;
the electron salt system comprises the following components in molar ratio: 2-15 alkali metals, 2-10 ethers and 2-10 alcohols in the alkali metal reagent.
2. The electronic salt system of claim 1, wherein:
the particle size of the alkali metal in the alkali metal dispersion is 5-100 μm.
3. A method of reducing an unsaturated hydrocarbon compound using the electron salt system of claim 1, wherein: the unsaturated hydrocarbon compound and the electron salt system are subjected to reduction reaction in an organic solvent, and the method comprises the following steps:
step S1: under the protection of nitrogen, mixing and stirring an alkali metal reagent, ethers and an organic solvent uniformly;
step S2: stirring and mixing unsaturated hydrocarbon compounds and alcohols uniformly, adding an organic solvent into a mixed solution of the unsaturated hydrocarbon compounds and the alcohols, and stirring and mixing uniformly to obtain a substrate solution;
step S3: mixing the substrate solution prepared in the step S2 with the alkali metal reagent and ether mixed solution prepared in the step S1 for reaction, and quenching the reaction to obtain a product to be treated;
step S4: extracting, drying an organic phase, concentrating and separating a product to be treated to obtain a reduction product of an unsaturated hydrocarbon compound;
wherein:
the organic solvent is one or a mixture of several of n-pentane, hexane, cyclohexane, diethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran and dioxane in any proportion;
the reaction temperature of the reduction reaction is-30 ℃ to 30 ℃.
4. A process for reducing an unsaturated hydrocarbon compound according to claim 3, wherein:
the unsaturated hydrocarbon compound is a substituted aromatic compound which reacts with an electron salt system in an organic solvent to generate a substituted cyclic olefin and alicyclic compound, and the reaction general formula is as follows:
Figure FDA0002704002870000021
alternatively, the first and second electrodes may be,
Figure FDA0002704002870000022
alternatively, the first and second electrodes may be,
Figure FDA0002704002870000023
wherein, R1 represents one of hydrogen, linear or branched alkyl, substituted or unsubstituted cycloalkyl, linear or branched alkenyl and substituted alkenyl; n is zero or a positive integer.
5. A process for reducing an unsaturated hydrocarbon compound according to claim 3, wherein:
the unsaturated hydrocarbon compound is an aromatic heterocyclic compound, the aromatic heterocyclic compound and an electron salt system react in an organic solvent to generate a substituted heterocyclic compound, and the reaction general formula is as follows:
Figure FDA0002704002870000031
wherein, R2 represents one of linear or branched alkyl, substituted or unsubstituted cycloalkyl, linear or branched alkenyl and substituted alkenyl; x represents an oxygen atom or a nitrogen atom, the number of oxygen atoms or nitrogen atoms in the heterocycle being equal to or greater than one; n is zero or a positive integer.
6. A process for reducing an unsaturated hydrocarbon compound according to claim 3, wherein:
the unsaturated hydrocarbon compound is alkyne or alkene, the alkyne or alkene reacts with the electron salt system in an organic solvent to generate an alkane compound, and the reaction general formula is as follows:
Figure FDA0002704002870000032
or
Figure FDA0002704002870000033
Wherein, R3 represents one of aryl, linear or branched alkyl, substituted or unsubstituted cycloalkyl, linear or branched alkenyl and substituted alkenyl; r4 represents one of aryl, linear or branched alkyl, substituted or unsubstituted cycloalkyl, linear or branched alkenyl and substituted alkenyl.
7. A process for reducing an unsaturated hydrocarbon compound according to claim 3, wherein:
the reaction time of the reduction reaction is 0.1-60 min.
8. A process for reducing an unsaturated hydrocarbon compound according to claim 3, wherein:
the molar ratio of the unsaturated hydrocarbon compound to the alkali metal in the alkali metal reagent is 1: 2-15;
the molar ratio of the unsaturated hydrocarbon compound to the ethers is 1: 2-10;
the molar ratio of the unsaturated hydrocarbon compound to the alcohol is 1: 2 to 10.
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Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Ammonia-free Birch reductions with sodium stabilized in silica gel, Na-SG(I);Costanzo, MJ;《Tetrahedron Letters》;20090805;第50卷(第39期);第5463-5466页 *
Compounds of Alkali Metal Anions;James L. Dye;《angewandte chemie international edition》;19790831;第18卷(第18期);第587-598页 *
在碱金属/液氨作用下两类还原反应的机理探讨;戴亚中等;《大学化学》;20150831;第30卷(第4期);第58-62页 *

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