CN108821966B - Method for synthesizing 3,3' - (1,4-phenylene) bis-glutaric acid - Google Patents

Method for synthesizing 3,3' - (1,4-phenylene) bis-glutaric acid Download PDF

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CN108821966B
CN108821966B CN201810562888.6A CN201810562888A CN108821966B CN 108821966 B CN108821966 B CN 108821966B CN 201810562888 A CN201810562888 A CN 201810562888A CN 108821966 B CN108821966 B CN 108821966B
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phenylene
bis
glutaric acid
symmetrical
bicyclohexanone
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CN108821966A (en
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陈超越
杨廷海
潘长多
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Jiangsu University of Technology
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
    • C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
    • C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
    • C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Abstract

The invention discloses a method for synthesizing 3,3' - (1,4-phenylene) bis-glutaric acid. The method comprises the following steps: firstly, terephthalaldehyde and ethyl acetoacetate are taken as starting materials, and a symmetrical bicyclohexanone structure (IV) is obtained by a series reaction process comprising Knoevcnagel condensation, Michael addition and intramolecular Aldol condensation under the catalysis of organic base; and (3) carrying out ring opening on the symmetrical bicyclohexanone compound (IV) under an alkaline condition through a reverse Aldol condensation reaction to form a chain intermediate tetrone (V), and then carrying out ketone decomposition on a substituted ethyl acetoacetate structural unit in the structure of the tetrone (V) to obtain the 3,3' - (1,4-phenylene) bis-glutaric acid (I). The preparation method has the advantages of cheap and easily obtained raw materials, no toxic or side effect, simple and convenient post-treatment, high yield and better industrial application value.

Description

Method for synthesizing 3,3' - (1,4-phenylene) bis-glutaric acid
Technical Field
The invention relates to a preparation method of a fine chemical intermediate, in particular to a method for synthesizing 3,3' - (1,4-phenylene) bis-glutaric acid.
Background
3,3'- (1,4-phenylene) dipentanoic acid (3,3' - (1,4-phenylene) dipentanoic acid) is an important intermediate for preparing high molecular materials such as polyamides, polyimides and polyesters, and for synthesizing organic charge transfer compounds. The structure is shown as the following formula (I):
Figure BDA0001683742700000011
there are two methods for synthesizing 3,3' - (1,4-phenylene) bis-glutaric acid reported so far:
(1) the following synthetic methods are disclosed in Journal of Polymer Science, Part A: Polymer Chemistry (1987),25(1),31-36 and Chemistry-A European Journal (2014),20(37), 11946-11953:
Figure BDA0001683742700000012
the method comprises the steps of firstly carrying out condensation reaction on terephthalaldehyde and ethyl cyanoacetate to obtain a compound (II), reacting the obtained condensation product (II) with Meldrum's acid (isopropylidene malonate) in an alkaline system, and finally acidifying with acetic acid to obtain 3,3' - (1,4-phenylene) bis-glutaric acid. The method needs to use the raw materials such as cyanoethyl acetate, Meldrum's acid and the like with higher price, and has higher cost; in addition, ethyl cyanoacetate has certain toxic and side effects, and in addition, the total yield of the route is only 36 percent, and the yield is not high.
(2) The following synthesis methods are disclosed in Chinese Journal of Chemistry (2004),22(11), 1330-:
Figure BDA0001683742700000021
the method also uses terephthalaldehyde as a starting material, firstly reacts with 10 times of cyanoacetic acid to obtain a tetracyano compound (III), and then is hydrolyzed and acidified to obtain 3,3' - (1,4-phenylene) bis-glutaric acid. The method needs cyanoacetic acid with higher price and toxic and side effects; further, the amount of cyanoacetic acid used is 10 times the amount of terephthalaldehyde, and it is necessary to consider post-treatment problems such as recovery of excessive cyanoacetic acid.
Disclosure of Invention
The invention aims to provide a method for synthesizing 3,3' - (1,4-phenylene) bis-glutaric acid, which has the advantages of cheap and easily obtained raw materials, no toxic or side effect, simple and convenient post-treatment and high yield.
The technical scheme adopted by the invention for solving the technical problems is as follows:
a method for synthesizing 3,3' - (1,4-phenylene) bis-glutaric acid, comprising the steps of:
(1) taking terephthalaldehyde and ethyl acetoacetate as initial raw materials, and obtaining a symmetrical dicyclohexyl ketone structure (IV) under the catalysis of organic base;
(2) decomposing a symmetrical bicyclohexanone compound (IV) under an alkaline condition to obtain 3,3' - (1,4-phenylene) bis-glutaric acid (I);
wherein the symmetrical bicyclohexanone structure (IV) and 3,3' - (1,4-phenylene) bis-glutaric acid (I) have the following structural formulas:
Figure BDA0001683742700000031
the method specifically comprises the following steps: taking terephthalaldehyde as a starting material, and carrying out a series reaction process comprising Knoevcnagel condensation-Michael addition-intramolecular Aldol condensation with ethyl acetoacetate to obtain a symmetrical bicyclohexanone structure (IV); and (3) carrying out ring opening on the symmetrical bicyclohexanone compound (IV) under an alkaline condition through a reverse Aldol condensation reaction to form a chain intermediate tetrone (V), and then carrying out ketone decomposition on a substituted ethyl acetoacetate structural unit in the structure of the tetrone (V) to obtain the 3,3' - (1,4-phenylene) bis-glutaric acid (I).
The synthetic route is as follows:
Figure BDA0001683742700000041
specifically, the molar ratio of the terephthalaldehyde to the ethyl acetoacetate in the step (1) is 1: 4-6.
Specifically, the organic base in the step (1) is one or two of diethylamine and 1, 8-diazabicyclo [5.4.0] undec-7-ene.
Specifically, the molar ratio of the organic base to the terephthalaldehyde in the step (1) is 1:2 to 1: 6.
Specifically, the alkaline condition in the step (2) is an inorganic alkaline condition.
Specifically, the inorganic base is sodium hydroxide and/or potassium hydroxide.
Specifically, the molar ratio of the symmetric bicyclohexanone compound (IV) to the inorganic base is 1: 10-30.
Specifically, the inorganic base is an inorganic base aqueous solution, and the mass fraction of the inorganic base aqueous solution is 40-60%.
The invention has the beneficial effects that: the invention does not use the more expensive ethyl cyanoacetate, cyanoacetic acid, Meldrum's acid and the like as raw materials, but uses the cheap and easily obtained ethyl acetoacetate without toxic and side effects as the raw material, thereby reducing the cost and improving the production safety. Meanwhile, the total yield of the 3,3' - (1,4-phenylene) bis-glutaric acid reaches 78.4%, the yield is improved, and the post-treatment is simple and convenient.
Detailed Description
The technical scheme provided by the invention is further detailed and completely described by combining the embodiment.
Example 1: synthesis of Compound IV
Terephthalaldehyde (26.83g,0.20mol) was dissolved in 150mL absolute ethanol, and ethyl acetoacetate (104.11g,0.80mol) was added. To the mixture was added 5mL of diethylamine under stirring, and the mixture was heated under reflux for 60min and then stirred at room temperature for 18 h. After 3h, crystals began to precipitate, and the mixture was stored in a refrigerator for 6 h. Filtering at 0 ℃, washing the solid with cold absolute ethyl alcohol to obtain white needle crystal which is the compound (IV), wherein the yield is as follows: 81.5 percent.1H NMR(400MHz,DMSO-d6)δ(ppm):7.19(s,4H),4.88(s,2H),3.91– 3.74(m,10H),3.72–3.64(m,2H),3.26(dd,J＝12.0,4.0Hz,2H),2.92 (d,J＝12.0Hz,2H),2.32(d,J＝12.0Hz,2H),1.23(s,6H),0.95(t,J＝8.0 Hz,6H),0.87(t,J＝8.0Hz,6H).13C NMR(100MHz,DMSO-d6)δ:203.43, 170.41,168.00,138.60,128.04,72.59,61.95,59.78,59.40,56.18,54.10, 39.94,28.25,13.82,13.76.HRMS(ESI)m/z Calcd.for C32H41O12: 617.6607[M-H]-；found:617.6610.
Example 2: synthesis of 3,3' - (1,4-phenylene) bis-glutaric acid
Compound IV (61.87g,0.10mol) was dissolved in 200mL of ethanol, 120mL of 50% by mass aqueous sodium hydroxide solution was added with stirring, and the reaction mixture was heated under reflux for 8 h. The resulting slurry was diluted with 200mL of water and concentrated in vacuo to remove ethanol.Then diluting with 200mL of water, adjusting the pH value to 1 by using concentrated hydrochloric acid, filtering the obtained solid, washing the solid with a small amount of cold water, and drying to obtain a light yellow solid, namely 3,3' - (1,4-phenylene) bis-glutaric acid, wherein the yield is 96.2%.1H NMR (400MHz,DMSO-d6)δ(ppm):12.04(s,4H),7.15(s,4H),3.45–3.35(m, 2H),2.86(d,J＝7.2Hz,8H).13C NMR(100MHz,DMSO-d6)δ(ppm): 172.2,141.6,127.5,40.2,37.5.HRMS(ESI)m/z Calcd.for C16H17O8: 337.0930[M-H]-；found:337.0934。
Example 3: synthesis of Compound IV
Terephthalaldehyde (26.83g,0.20mol) was dissolved in 150mL absolute ethanol and ethyl acetoacetate (156.17g,1.2mol) was added. To the above mixture was further added 12mL of 1, 8-diazabicycloundec-7-ene with stirring, and the mixture was heated under reflux for 60min and then stirred at room temperature for 18 h. After 3h, crystals began to precipitate, and the mixture was stored in a refrigerator for 6 h. Filtering at 0 ℃, washing the solid with cold absolute ethyl alcohol to obtain white needle crystal which is the compound (IV), wherein the yield is as follows: 82.2 percent.
The nuclear magnetic data were as in example 1.
Example 4: synthesis of 3,3' - (1,4-phenylene) bis-glutaric acid
Compound IV (61.87g,0.10mol) was dissolved in 200mL of ethanol, 180mL of an aqueous 40% by mass potassium hydroxide solution was added with stirring, and the reaction mixture was heated under reflux for 8 h. The resulting slurry was diluted with 200mL of water and concentrated in vacuo to remove ethanol. Then diluting with 200mL of water, adjusting the pH value to 2 by using concentrated hydrochloric acid, carrying out suction filtration on the obtained solid, washing with a small amount of cold water, and drying to obtain a light yellow solid, namely 3,3' - (1,4-phenylene) bis-glutaric acid, wherein the yield is 95.0%.
The nuclear magnetic data were as in example 2.
In light of the foregoing description of the preferred embodiment of the present invention, many modifications and variations will be apparent to those skilled in the art without departing from the spirit and scope of the invention. The technical scope of the present invention is not limited to the content of the specification, and must be determined according to the scope of the claims.

Claims (5)

1. A method for synthesizing 3,3' - (1,4-phenylene) bis-glutaric acid, comprising the steps of:
(1) with terephthalaldehyde
And acetoacetic acid ethyl ester
Heating and stirring the raw materials under the catalysis of organic base to obtain a symmetrical dicyclohexyl ketone structure (IV);
(2) decomposing a symmetrical bicyclohexanone compound (IV) under an alkaline condition to obtain 3,3' - (1,4-phenylene) bis-glutaric acid (I);
wherein the symmetrical bicyclohexanone structure (IV) and 3,3' - (1,4-phenylene) bis-glutaric acid (I) have the following structural formulas:
Figure FDA0002968298530000011
the molar ratio of the terephthalaldehyde to the ethyl acetoacetate in the step (1) is 1: 4-6;
the organic base in the step (1) is one or two of diethylamine and 1, 8-diazabicyclo [5.4.0] undec-7-ene;
the molar ratio of the organic alkali to the terephthalaldehyde in the step (1) is 1: 2-1: 6.
2. A process for the synthesis of 3,3' - (1,4-phenylene) bis-glutaric acid as claimed in claim 1, wherein: and (3) adding an inorganic alkali solution to form an alkaline condition in the step (2).
3. A process as claimed in claim 2 for the synthesis of 3,3' - (1,4-phenylene) bis glutaric acid wherein: the inorganic alkali is sodium hydroxide and/or potassium hydroxide.
4. A process as claimed in claim 2 for the synthesis of 3,3' - (1,4-phenylene) bis glutaric acid wherein: the molar ratio of the symmetrical bicyclohexanone compound (IV) to the inorganic base is 1: 10-30.
5. A process as claimed in claim 2 for the synthesis of 3,3' - (1,4-phenylene) bis glutaric acid wherein: the inorganic alkaline solution is an inorganic alkaline water solution, and the mass fraction of the inorganic alkaline water solution is 40-60%.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101993426A (en) * 2009-08-31 2011-03-30 四川大学 3-aryl glutaric acid mono-amide compound as well as preparation method and application thereof
CN102381961A (en) * 2011-09-03 2012-03-21 四川大学 3-phenyl glutaric acid compound, preparation method and purpose thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101993426A (en) * 2009-08-31 2011-03-30 四川大学 3-aryl glutaric acid mono-amide compound as well as preparation method and application thereof
CN102381961A (en) * 2011-09-03 2012-03-21 四川大学 3-phenyl glutaric acid compound, preparation method and purpose thereof

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* Cited by examiner, † Cited by third party
Title
"Aliphatic Polyimides from Phenylene Bis( Succinic Anhydride) and Bis( glutaric anhydride) ";Yonezawa等;《Journal of Polymer Science: Part A:Polymer Chemistry》;19870131;第25卷;第33页scheme 1、第31页第3段EXPERIMENTAL material、第32页第1-2段 *
"Modified Synthesis of NOP Receptor Antagonist SB612111";David A.Perrey等;《Synthesis》;20161219;第49卷;第1395页右栏Scheme3 *
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