Method for preparing five-membered ring diene compound through inverse D-A reaction

Abstract

The invention discloses a preparation method for preparing a five-membered ring diene compound through a reverse D-A reaction, and the preparation method comprises the following steps: under a vacuum condition, carrying out a reaction on a substituted bicyclo [2, 2, 1] heptyl-2-ene compound to obtain the five-membered ring diene compound. According to the method, the bicyclo [2, 2, 1] hept-2-ene compound is heated under the continuous vacuumizing condition, a gas product is rapidly moved out of a reaction system, and the decomposition reaction is balanced and moves rightwards, so that the bicyclo [2, 2, 1] hept-2-ene compound can be completely decomposed at a relatively mild temperature, and the energy consumption is reduced.

Description

Technical Field

[0001] The present application relates to a method for preparing a five-membered ring diene compound by reverse DA reaction, belonging to the technical field of organic synthesis. Background Art

[0002] Five-membered ring diene compounds include cyclopentadiene, furan, thiophene, pyrrole and their derivatives. In addition to obtaining them through processing of natural products, their industrial production methods include substitution, condensation cyclization and other methods to prepare corresponding products substituted at specific positions. Among them, the reverse Diels-Alder reaction of substituted bicyclic [2,2,1] hept-2-ene compounds is also a simple and effective method to obtain such compounds. Such raw materials can be obtained through Diels-Alder reaction and selective hydrogenation. However, the synthetic technology using this method has not been thoroughly studied. The reason is that such reactions are reversible in themselves and difficult to completely convert. They need to be separated from another product produced by decomposition. In actual operation, high temperatures of more than 200°C are usually required to completely convert the raw materials, which consumes a lot of energy and is highly dangerous. The products are prone to side reactions such as polymerization at high temperatures. These harsh conditions limit their large-scale production applications. There is still a lack of a relatively mild and efficient production method in this field. Summary of the invention

[0003] According to one aspect of the present application, a method for preparing a five-membered ring diene compound by a reverse DA reaction is provided, the preparation method comprising:

[0004] Under continuous vacuum conditions, a substituted bicyclo[2,2,1]hept-2-ene compound is reacted to obtain a five-membered ring diene compound;

[0005] The substituted bicyclo[2,2,1]hept-2-ene compound has a structure shown in Formula I;

[0006] The five-membered ring diene compound has a structure shown in Formula II:

[0007]

[0008] In Formula I and Formula II, R1, R2, R3, and R4 are independently selected from one of -H, -NO2, -SO3R, -F, -Cl, -Br, -I, -CO2R, -OR, -CH2OR, -CH2R, -CF3, and -C6H4R;

[0009] R is selected from one of hydrogen, -CH3, -C2H5, -C3H7, -C4H9;

[0010] In Formula I and Formula II, X is selected from one of -CH2, -NH, -O, and -S;

[0011] In Formula I, R' and R" are independently selected from one of hydrogen, methyl and ethyl.

[0012] A method for preparing a five-membered ring aromatic compound by reverse Diels-Alder reaction at low temperature, comprising the following steps:

[0013] A substituted bicyclo[2,2,1]hept-2-ene substrate is placed in a container, the reaction container is continuously vacuumed, and the reaction container is heated.

[0014] Optionally, the container used for the reaction is selected from a round-bottom flask, a two-necked flask, a three-necked flask, a Schlenk tube, and a Schlenk bottle.

[0015] Optionally, the reaction temperature is 150-200°C.

[0016] Optionally, the reaction temperature is selected from any value of 150°C, 160°C, 170°C, 180°C, 190°C, 200°C or a range between any two of the above values.

[0017] Optionally, the reaction is heated in an oil bath or heating mantle.

[0018] Optionally, the reaction time is 2 to 48 hours.

[0019] Optionally, the reaction time is selected from any value of 2h, 4h, 6h, 8h, 12h, 24h, 48h or a range between any two of the above.

[0020] Optionally, the vacuum degree of the reaction is -0.08 to -0.1 MPa.

[0021] Optionally, the reaction is carried out under magnetic stirring or mechanical stirring.

[0022] Optionally, during the reaction, the stirring speed is 200 to 800 rpm.

[0023] Optionally, the stirring speed is any value among 200 rpm, 300 rpm, 400 rpm, 500 rpm, 600 rpm, 700 rpm, 800 rpm or a range value between any two of the above.

[0024] Optionally, the reaction is carried out without solvent.

[0025] The reaction formula for preparing five-membered ring aromatic compounds by reverse Diels-Alder reaction is as follows:

[0026]

[0027] in,

[0028] R1, R2, R3, R4=-H, -OH, -NO2, -SO3R, -F, -Cl, -Br, -I, -CO2H, -CO2R, -OR, -CH2OR, -CH3, -CH2R, -CF3, -C6H4R, etc.;

[0029] R is selected from one of hydrogen, -CH3, -C2H5, -C3H7, -C4H9;

[0030] R', R”=-H, -CH3, -C2H6;

[0031] X=CH2, NH, O, S.

[0032] In the present application, the terms "methyl" and "ethyl" refer to groups formed by losing any hydrogen atom from a molecule of a methane or ethane compound.

[0033] The beneficial effects of this application include:

[0034] The present application heats a bicyclo[2,2,1]hept-2-ene compound under continuous vacuum conditions, quickly removes the gaseous product from the reaction system, and shifts the decomposition reaction equilibrium to the right, so that it can be completely decomposed at a relatively mild temperature, saving energy consumption. By utilizing the fact that another product in the decomposition reaction is a highly volatile gas, the gaseous product in the reverse Diels-Alder reaction is quickly removed by vacuuming and continuously applying negative pressure to the reaction system, so that the reaction equilibrium is greatly shifted to the right, thereby reducing the temperature required for the reaction at normal pressure and saving energy consumption. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 This is a diagram of the device for preparing five-membered ring diene compounds by reverse DA reaction in this application. DETAILED DESCRIPTION

[0036] The present application is described in detail below with reference to embodiments, but the present application is not limited to these embodiments.

[0037] Unless otherwise specified, the raw materials in the examples of this application were purchased through commercial channels.

[0038] Unless otherwise specified, the substrates involved in this application are all prepared by Diels-Alder reaction, and the reaction formula is as follows:

[0039]

[0040] in,

[0041] R1, R2, R3, R4=-H, -OH, -NO2, -SO3R, -F, -Cl, -Br, -I, -CO2H, -CO2R, -OR, -CH2OR, -CH3,, -CH2R, -CF3, -C6H4R, etc.;

[0042] R is selected from one of hydrogen, -CH3, -C2H5, -C3H7, -C4H9;

[0043] R', R”=-H, -CH3, -C2H6;

[0044] X=CH2, NH, O, S.

[0045] Gas phase analysis was performed using Agilent 7890A GC

[0046] The conversion rate and product yield in the examples of this application are calculated as follows:

[0047] Conversion rate [mol%] = (n0-n) / n0×100%

[0048] Product yield [mol%] = n x / n0×100%

[0049] In the formula, n0 is the amount of substrate (calculated as olefin) added before the reaction [mol], n is the amount of substrate remaining after the reaction [mol], and n x The amount of product produced during the reaction [mol].

[0050] Example 1: Preparation of diethyl cyclopenta-2,5-diene-1,2-dicarboxylate

[0051] Use Figure 1 The reaction device shown in the figure, add 5mmol of diethyl bicyclo[2.2.1]hept-2-ene-2,3-dicarboxylate in a 30mL Schlenk tube, use a water pump to continuously evacuate, and heat the oil bath at 160°C for 12h. After the reaction is completed, the reaction device is returned to normal temperature and pressure, dissolved with ethyl acetate and qualitatively analyzed by GC, and the raw material is completely consumed, that is, the conversion rate is 100%. The reaction product is separated by column chromatography (petroleum ether: ethyl acetate = 5:1), and the yield of the product cyclopenta-2,5-diene-1,2-dicarboxylate is 98%.

[0052] The reaction formula is as follows:

[0053]

[0054] Example 2-5: Preparation of dimethyl 3,4-furandicarboxylate

[0055] Add 5 mmol of raw material (Example 2 is 7-oxabicyclo[2.2.1]hept-2-ene-2,3-dicarboxylic acid dimethyl ester, and Example 3-5 is its homologue) to a 30 mL Schlenk tube, use a water pump to continuously evacuate, and heat the oil bath at 160° C. for 10 hours. After the reaction is completed, the reaction device is returned to normal temperature and pressure, dissolved with ethyl acetate and qualitatively analyzed by GC. The raw material is completely consumed, that is, the conversion rate is 100%. The reaction product is separated by column chromatography (petroleum ether: ethyl acetate = 5:1), and the specific results are shown in Table 1.

[0056] The reaction formula is as follows:

[0057]

[0058] Table 1

[0059] Example R’ R” Yield of dimethyl 3,4-furandicarboxylate (%) 2 H H 93 3 <![CDATA[CH3]]> H 95 4 <![CDATA[C2H6]]> H 91 5 <![CDATA[CH3]]> <![CDATA[CH3]]> 92

[0060] Example 6-9: Preparation of 3,4-dihexyl-1H-pyrrole

[0061] Add 5 mmol of raw material (Example 6 is 2,3-dihexyl-7-azabicyclo[2.2.1]hept-2-ene, and Example 7-9 is its homologue) to a 30 mL Schlenk tube, use a water pump to continuously evacuate, and heat the oil bath at 170°C for 8 hours. After the reaction is completed, the reaction device is returned to normal temperature and pressure, dissolved in ethyl acetate and qualitatively analyzed by GC. The raw material is completely consumed, that is, the conversion rate is 100%. The reaction product is separated by column chromatography (petroleum ether: ethyl acetate = 2:1), and the specific results are shown in Table 2.

[0062] The reaction formula is as follows:

[0063]

[0064] Table 2

[0065]

[0066]

[0067] Example 10-13: Preparation of diethyl 3,4-thiophenedicarboxylate

[0068] Add 5 mmol of raw material (Example 10 is 7-thiobicyclo[2.2.1]hept-2-ene-2,3-dicarboxylic acid diethyl ester, and Examples 11-13 are its homologues) to a 30 mL Schlenk tube, use a water pump to continuously evacuate, and heat the oil bath at 160° C. for 6 hours. After the reaction is completed, the reaction device is returned to normal temperature and pressure, dissolved in ethyl acetate and qualitatively analyzed by GC. The raw material is completely consumed, that is, the conversion rate is 100%. The reaction product is separated by column chromatography (petroleum ether: ethyl acetate = 5:1), and the specific results are shown in Table 3.

[0069] The reaction formula is as follows:

[0070]

[0071] Table 3

[0072] Example R’ R” Yield of diethyl 3,4-thiophenedicarboxylate (%) 10 H H 96 11 <![CDATA[CH3]]> H 95 12 <![CDATA[C2H6]]> H 99 13 <![CDATA[CH3]]> <![CDATA[CH3]]> 98

[0073] Embodiment 14

[0074] 5 mmol of 7-oxabicyclo[2.2.1]hept-2-ene-2,3-dicarboxylic acid dimethyl ester was added to a 30 mL Schlenk tube, and a water pump was used to continuously evacuate the tube while heating the tube in an oil bath at 120°C for 4 hours. After the reaction, the reaction apparatus was returned to normal temperature and pressure, dissolved with methyl acetate, and analyzed by GC. The raw material did not decompose, and no dimethyl 3,4-furandicarboxylate was detected.

[0075] Embodiment 15

[0076] 5 mmol of 7-oxabicyclo[2.2.1]hept-2-ene-2,3-dicarboxylic acid dimethyl ester was added to a 30 mL Schlenk tube, and a water pump was used to continuously evacuate the mixture, and the mixture was heated in an oil bath at 210° C. for 2 h. After the reaction, the reaction apparatus was returned to normal temperature and pressure, dissolved with methyl acetate, and qualitatively analyzed by GC. The raw material was completely consumed, i.e., the conversion rate was 100%. The reaction product was separated by column chromatography (petroleum ether: ethyl acetate = 5:1), and the yield of the product 3,4-furandicarboxylic acid dimethyl ester was 78%.

[0077] The above are only a few embodiments of the present application and do not constitute any form of limitation to the present application. Although the present application is disclosed as above with preferred embodiments, it is not intended to limit the present application. Any technician familiar with the profession, without departing from the scope of the technical solution of the present application, using the technical content disclosed above to make slight changes or modifications are equivalent to equivalent implementation cases and fall within the scope of the technical solution.

Claims

1. A method for preparing a five-membered ring diene compound by reverse DA reaction, characterized in that: The preparation method comprises: Under continuous vacuum conditions, a substituted bicyclo[2,2,1]hept-2-ene compound is reacted to obtain a five-membered ring diene compound; The substituted bicyclo[2,2,1]hept-2-ene compound has a structure shown in Formula I; The five-membered ring diene compound has a structure shown in Formula II: In Formula I and Formula II, R1, R2, R3, and R4 are independently selected from one of -H, -NO2, -SO3R, -F, -Cl, -Br, -I, -CO2R, -OR, -CH2OR, -CH2R, -CF3, and -C6H4R; R is selected from one of hydrogen, -CH3, -C2H5, -C3H7, -C4H9; In Formula I and Formula II, X is selected from one of -CH2, -NH, -O, and -S; In Formula I, R' and R" are independently selected from one of hydrogen, methyl and ethyl.

2. The preparation method according to claim 1, characterized in that: The reaction temperature is 150-200°C.

3. The preparation method according to claim 1, characterized in that: The reaction time is 2 to 48 hours.

4. The preparation method according to claim 1, characterized in that: The vacuum degree of the reaction is -0.08 to -0.1 MPa.

5. The preparation method according to claim 1, characterized in that: During the reaction, the stirring speed is 200-800 rpm.

6. The preparation method according to claim 1, characterized in that: There was no solvent in the reaction.

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