CN110627732A - Method for synthesizing nitroquinoxaline or derivative thereof and aminoquinoxaline or derivative thereof - Google Patents

Method for synthesizing nitroquinoxaline or derivative thereof and aminoquinoxaline or derivative thereof Download PDF

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CN110627732A
CN110627732A CN201910966508.XA CN201910966508A CN110627732A CN 110627732 A CN110627732 A CN 110627732A CN 201910966508 A CN201910966508 A CN 201910966508A CN 110627732 A CN110627732 A CN 110627732A
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derivative
nitro
nitroquinoxaline
aminoquinoxaline
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路庆华
刘团青
张书宇
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Tongji University
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Tongji University
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
    • B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
    • B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
    • B01J31/0271—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds also containing elements or functional groups covered by B01J31/0201 - B01J31/0231
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
    • C07C201/06—Preparation of nitro compounds
    • C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/42—Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2231/00—Catalytic reactions performed with catalysts classified in B01J31/00
    • B01J2231/40—Substitution reactions at carbon centres, e.g. C-C or C-X, i.e. carbon-hetero atom, cross-coupling, C-H activation or ring-opening reactions
    • B01J2231/42—Catalytic cross-coupling, i.e. connection of previously not connected C-atoms or C- and X-atoms without rearrangement
    • B01J2231/4277—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues
    • B01J2231/4283—C-X Cross-coupling, e.g. nucleophilic aromatic amination, alkoxylation or analogues using N nucleophiles, e.g. Buchwald-Hartwig amination

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  • Materials Engineering (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

The present application relates to a method for synthesizing nitroquinoxaline or a derivative thereof, which comprises reacting a mononitro-substituted o-phenylenediamine or a derivative thereof with a mononitro-substituted benzil or a derivative thereof in a solvent in the presence of a catalyst, o-benzoylsulfimide, for a predetermined period of time to obtain the nitroquinoxaline or the derivative thereof. The present application also provides a method of synthesizing aminoquinoxaline or a derivative thereof. The application also provides an application of the o-benzoylsulfimide as a catalyst in synthesizing nitroquinoxaline or derivatives thereof. The application also provides a method for preparing the 4-nitrobenzoyl. The synthesis process has low cost and high yield, and is favorable for realizing large-scale preparation of the nitroquinoxaline or the derivative thereof and the aminoquinoxaline or the derivative thereof.

Description

Method for synthesizing nitroquinoxaline or derivative thereof and aminoquinoxaline or derivative thereof
Technical Field
The application relates to the technical field of organic synthesis, in particular to a method for synthesizing nitroquinoxaline or derivatives thereof and aminoquinoxaline or derivatives thereof.
Background
Quinoxaline is a benzopyrazine compound having excellent biological activity and thermal stability, and has been widely studied because it exists in various compounds and is expected to be used in the fields of dyes, organic semiconductors, electroluminescent materials, anion receptors, and the like. Similarly, quinoxaline derivatives are potentially applicable in many fields. Therefore, many methods have been developed in the art for synthesizing quinoxaline derivatives, for example, reacting a monomer containing an o-phenylenediamine structure with an α -hydroxyketone or an epoxide, etc.
Aminoquinoxaline has a higher chemical bond energy, a larger molar volume and a weaker polarity, which endows a polymer prepared from the aminoquinoxaline with excellent heat resistance and oxidation resistance, higher environmental stability, a low dielectric constant, dielectric loss and higher plasticity. The aminoquinoxaline can be dissolved in an organic solvent and has good processing performance.
The mixture of 2- (4-aminophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-aminophenyl) -2-phenyl-6-aminoquinoxaline is a novel aminoquinoxaline diamine monomer. Polymers such as quinoxaline polyimide, polyether, polyester and the like synthesized by the mixture have good thermal stability, chemical stability, excellent conductivity, good air permeability and toughness. In addition, the mixture has good solubility in organic solvents, low crystallinity and a wider processing window.
Chinese patent publication CN105153144A discloses a main chain diamine quinoxalinyl benzoxazine and a preparation method thereof, wherein 4-nitrophenyl coupling, 4-nitro o-phenylenediamine and glacial acetic acid are used as starting materials, a mixture of 2- (4-nitrophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-nitrophenyl) -2-phenyl-6-aminoquinoxaline is synthesized firstly, and the yield is 81%. Then, the mixture of 2- (4-aminophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-aminophenyl) -2-phenyl-6-aminoquinoxaline is obtained by hydrazine hydrate reduction. The process disclosed in the patent document has disadvantages that the yield of the mixture of nitroquinoxalines is not high, and the starting material 4-nitrobenzoyl is expensive and not easily available, resulting in high production cost and unsuitability for industrial production.
Chinese invention patent publication CN107089954A discloses a method for synthesizing a mixture of 2- (4-aminophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-aminophenyl) -2-phenyl-6-aminoquinoxaline, which comprises (1) obtaining 4-nitrophenylacetyl chloride by chlorination reaction with 4-nitrophenylacetic acid as a starting material; (2) reacting 4-nitrophenylacetyl chloride with benzene to obtain 2- (4-nitrophenyl) -1-acetophenone; (3) reacting 2- (4-nitrophenyl) -1-acetophenone with 4-nitro-o-phenylenediamine to obtain a mixture of 2- (4-nitrophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-nitrophenyl) -2-phenyl-6-aminoquinoxaline; and (4) carrying out catalytic hydrogenation on the nitroquinoxaline mixture in the step (3) to obtain a mixture of 2- (4-aminophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-aminophenyl) -2-phenyl-6-aminoquinoxaline. The synthesis method disclosed in the patent document does not use 4-nitrobenzoyl, and reduces the production cost to some extent. However, step (3) of the process needs to be carried out at a relatively high temperature of 70-80 ℃ in the presence of a gaseous oxidant and a basic catalyst, with a yield between 90.1% and 95.0%.
For this reason, there is a continuous need in the art to develop a low-cost, high-yield method for synthesizing nitroquinoxaline or a derivative thereof and aminoquinoxaline or a derivative thereof.
Disclosure of Invention
The present application aims to provide a method for synthesizing nitroquinoxaline or a derivative thereof at a low cost and a high yield, thereby solving the above-mentioned technical problems in the prior art. Specifically, 4-nitro iodobenzene and phenylacetylene are used as starting materials to economically and efficiently synthesize 4-nitro benzil. Then, a mixture of 2- (4-nitrophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-nitrophenyl) -2-phenyl-6-aminoquinoxaline is prepared by reacting 4-nitrophenyl benzil with 4-nitrophthalimide at normal temperature and pressure in a yield of up to 98% using o-benzoylsulfonylimide (also called saccharin) as a specific catalyst. Finally, a mixture of 2- (4-aminophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-aminophenyl) -2-phenyl-6-aminoquinoxaline is prepared by a catalytic hydrogenation method.
It is also an object of the present application to provide a method for the synthesis of nitro-substituted benzils.
It is also an object of the present application to provide a method for synthesizing aminoquinoxaline or a derivative thereof.
The application also aims to provide an application of the o-benzoylsulfonyl imide as a catalyst in the preparation of nitroquinoxaline or derivatives thereof.
It is also an object of the present application to provide a process for the preparation of 4-nitrobenzoyl.
In order to solve the above technical problem, the present application provides the following technical solutions:
in a first aspect, the present application provides a method for synthesizing nitroquinoxaline or a derivative thereof, characterized in that the method comprises the steps of: reacting a mononitro-substituted o-phenylenediamine or derivative thereof with a mononitro-substituted benzil or derivative thereof in a solvent in the presence of a catalyst, o-benzoylsulfimide, for a predetermined period of time to obtain said nitroquinoxaline or derivative thereof;
wherein the mononitro-substituted o-phenylenediamine or derivative thereof has a structure represented by the following general formula (I):
in formula (I), the groups R1, R2, R3 and R4 are each independently selected from H, C1-C10 alkyl or nitro, and only one and one of the groups R1, R2, R3 and R4 is nitro;
wherein the mononitro-substituted benzil has a structure represented by the following general formula (II):
in general formula (II), the groups R5, R6, R7, R8, R9, R10, R11, R12, R13 and R14 are each independently selected from H, C1-C10 alkyl or nitro, and one and only one of the groups R5, R6, R7, R8, R9, R10, R11, R12, R13 and R14 is nitro;
wherein the nitroquinoxaline or the derivative thereof has a structure represented by the following general formula (III):
in formula (III), the groups R21, R22, R23 and R24 are each independently selected from H, C1-C10 alkyl or nitro, and one and only one of the groups R21, R22, R23 and R24 is nitro; in general formula (III), the groups R31, R32, R33, R34, R35, R41, R42, R43, R44 and R45 are each independently selected from H, C1-C10 alkyl or nitro, and one and only one of the groups R31, R32, R33, R34, R35, R41, R42, R43, R44 and R45 is nitro.
In one embodiment of the first aspect, the mononitro-substituted benzil or derivative thereof comprises 4-nitrobenzoyl, 3-nitrobenzoyl, 2-methyl-4-nitrobenzoyl, 3-methyl-4-nitrobenzoyl, 2, 3-dimethyl-4-nitrobenzoyl, 2,3, 5-trimethyl-4-nitrobenzoyl;
and/or the mononitro-substituted o-phenylenediamine or the derivative thereof is 3-nitrophthalenediamine, 4-nitrophthalenediamine, 5-nitrophthalenediamine, 6-nitrophthalenediamine, 3-methyl-4-nitrophthalenediamine, 5-methyl-4-nitrophthalenediamine, 3, 5-dimethyl-4-nitrophthalenediamine or 3,5, 6-trimethyl-4-nitrophthalenediamine;
and/or the solvent is one or more of glacial acetic acid, methanol, N N-dimethylformamide or acetonitrile.
In one embodiment of the first aspect, the catalyst is present in an amount of less than or equal to 5% o/f on a molar basis of the benzoylsulfonimide and the mononitro-substituted benzil.
In one embodiment of the first aspect, the nitroquinoxaline or derivative thereof comprises a mixture of 2- (4-nitrophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-nitrophenyl) -2-phenyl-6-aminoquinoxaline.
In one embodiment of the first aspect, the 4-nitrobenzoyl is prepared by the following process:
(1) reacting nitrohalogenated benzene with phenylacetylene to obtain 1-nitro-4-phenylacetylene; and
(2) reacting 1-nitro-4-phenylacetylene with an oxidant in the presence of a metal catalyst to obtain the 4-nitrobenzoyl.
In one embodiment of the first aspect, the nitrohalobenzene is 4-nitroiodobenzene, 4-nitrobromobenzene or 4-nitrochlorobenzene;
and/or the metal catalyst is palladium dichloride or a mixture of aluminum chloride and palladium acetate in equimolar amount;
and/or the oxidizing agent is dimethyl sulfoxide.
In a second aspect, the present application provides a method for synthesizing an aminoquinoxaline or a derivative thereof, characterized in that the method comprises reducing a nitro group corresponding to a nitroquinoxaline or a derivative thereof prepared by the method for synthesizing a nitroquinoxaline or a derivative thereof according to claim 1 to an amino group to obtain the aminoquinoxaline or the derivative thereof.
In one embodiment of the second aspect, the aminoquinoxaline or derivative thereof is a mixture of 2- (4-aminophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-aminophenyl) -2-phenyl-6-aminoquinoxaline.
In a third aspect, the present application provides the use of a phthalimide as a catalyst in the synthesis of nitroquinoxaline or a derivative thereof.
In a fourth aspect, the present application provides a process for preparing 4-nitrobenzoyl comprising the steps of:
(1) reacting nitrohalogenated benzene with phenylacetylene to obtain 1-nitro-4-phenylacetylene; and
(2) reacting 1-nitro-4-phenylacetylene with an oxidant in the presence of a metal catalyst to obtain the 4-nitrobenzoyl.
Compared with the prior art, the method has the beneficial effects that the synthesis process is low in cost and high in yield, and is beneficial to realizing large-scale preparation of the nitroquinoxaline or the derivative thereof and the aminoquinoxaline or the derivative thereof.
Drawings
FIG. 1 shows a hydrogen nuclear magnetic resonance spectrum of 1-nitro-4-phenylacetylene benzene.
FIG. 2 shows a hydrogen nuclear magnetic resonance spectrum of 4-nitrobenzoyl.
FIG. 3 shows the hydrogen nuclear magnetic resonance spectra of a mixture of two isomers, 2- (4-nitrophenyl) -3-phenyl-6-nitroquinoxaline and 3- (4-nitrophenyl) -2-phenyl-6-nitroquinoxaline, according to example 1, in a molar ratio of 1: 1.
FIG. 4 shows the hydrogen nuclear magnetic resonance spectra of a mixture of two isomers, 2- (4-aminophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-aminophenyl) -2-phenyl-6-aminoquinoxaline, according to example 1, in a molar ratio of 1: 1.
Detailed Description
The aminoquinoxaline or the derivative thereof is a novel diamine monomer, and the polyimide, polyether, polyester and other polymers synthesized by utilizing the aminoquinoxaline have excellent thermal stability and chemical stability. Nitroquinoxaline or a derivative thereof is a precursor compound for synthesizing aminoquinoxaline or a derivative thereof, and a process for converting nitro group into amino group, such as catalytic hydrogenation reduction, hydrazine hydrate reduction and the like, is well established in the industry. However, the process for synthesizing nitroquinoline or derivatives thereof in the prior art has high cost, low reaction yield and harsh reaction conditions. Therefore, there is a continuing need in the art to develop a low-cost, high-yield method for synthesizing nitroquinoxaline or a derivative thereof.
The application provides a method for synthesizing nitroquinoxaline or a derivative thereof, which is characterized by comprising the following steps: reacting a mononitro-substituted o-phenylenediamine or derivative thereof with a mononitro-substituted benzil or derivative thereof in a solvent in the presence of a catalyst, o-benzoylsulfimide, for a predetermined period of time to obtain said nitroquinoxaline or derivative thereof;
wherein the mononitro-substituted o-phenylenediamine or derivative thereof has a structure represented by the following general formula (I):
in formula (I), the groups R1, R2, R3 and R4 are each independently selected from H, C1-C10 alkyl or nitro, and only one and one of the groups R1, R2, R3 and R4 is nitro;
wherein the mononitro-substituted benzil has a structure represented by the following general formula (II):
in general formula (II), the groups R5, R6, R7, R8, R9, R10, R11, R12, R13 and R14 are each independently selected from H, C1-C10 alkyl or nitro, and one and only one of the groups R5, R6, R7, R8, R9, R10, R11, R12, R13 and R14 is nitro;
wherein the nitroquinoxaline or the derivative thereof has a structure represented by the following general formula (III):
in formula (III), the groups R21, R22, R23 and R24 are each independently selected from H, C1-C10 alkyl or nitro, and one and only one of the groups R21, R22, R23 and R24 is nitro; in general formula (III), the groups R31, R32, R33, R34, R35, R41, R42, R43, R44 and R45 are each independently selected from H, C1-C10 alkyl or nitro, and one and only one of the groups R31, R32, R33, R34, R35, R41, R42, R43, R44 and R45 is nitro.
In one embodiment, the arrow in the formula (III) indicates the simultaneous presence of two isomers, specifically a mixture of isomers composed of the interchanging of substituents at the 2-and 3-positions on the nitrogen-containing six-membered ring of quinoxaline.
As used herein, the term "C1-C10 alkyl" refers to a straight or branched alkyl group having from 1 to 10 carbon atoms. In one embodiment, the C1-C10 alkyl group includes methyl, ethyl, propyl, isopropyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, or decyl, and the like.
In a particularly preferred embodiment, the nitroquinoline or derivative thereof is a mixture of 2- (4-nitrophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-nitrophenyl) -2-phenyl-6-aminoquinoxaline.
In a particularly preferred embodiment, the aminoquinoline or derivative thereof is a mixture of 2- (4-aminophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-aminophenyl) -2-phenyl-6-aminoquinoxaline.
In another embodiment, the inventors of the present application have surprisingly found that the yield of the reaction between mononitrosubstituted benzil and mononitrosubstituted o-phenylenediamine is significantly increased with very low amounts of phthalimide (also known as saccharin), which is commonly used as a sweetener.
The application also provides a method for economically and efficiently synthesizing the 4-nitrobenzoyl. The method may comprise the steps of: (1) reacting nitrohalogenated benzene with phenylacetylene to obtain 1-nitro-4-phenylacetylene; and (2) reacting 1-nitro-4-phenylacetylene with an oxidant in the presence of a metal catalyst to obtain the 4-nitrobenzoyl.
In one embodiment, the palladium chloride is replaced by equimolar amounts of aluminum chloride and palladium acetate in the preparation of benzil, but the yields of aluminum chloride and palladium acetate as catalysts are low (around 40%).
In one embodiment, higher yields can be achieved without the use of a catalyst at different temperatures and durations: the yield can reach 98 percent after the reaction for 12 hours at normal temperature by taking glacial acetic acid as a solvent; the yield can reach 98 percent after the reaction is carried out for 12 hours at the temperature of 64 ℃ by taking methanol as a solvent under heating and refluxing; the yield can be more than 80% after 36h reaction at 90 ℃ by using DMF as a solvent, and the yield can be more than 60% after 36h reaction at 90 ℃ by using acetonitrile as a solvent. The reaction time can be shortened to 1h by using saccharin as a catalyst in the presence of 5% of glacial acetic acid as a solvent.
Examples
The present application will now be described and illustrated in further detail with reference to the following examples. All chemical raw materials can be purchased from the market unless otherwise specified. Those skilled in the art will appreciate that the following embodiments are exemplary only.
Example 1
The synthetic route of this example is as follows:
hereinafter, the nuclear magnetic resonance spectrometer used is a bruker 500M nuclear magnetic resonance spectrometer.
In the nuclear magnetic data described below, it is,1H NMR(CDCl3400MHz) represents the hydrogen nuclear magnetic resonance spectrum at 400MHz using deuterated chloroform as a solvent.1H NMR (DMSO-d6,500MHz) represents a nuclear magnetic resonance hydrogen spectrum at 500MHz in deuterated DMSO as a solvent.
Step 1: synthesis of 1-nitro-4-phenylacetylene benzene
12.5g (50mmol) of 4-nitroiodobenzene, 6.5mL (60mmol) of phenylacetylene, 112.3mg (0.5mmol) of palladium acetate, 95.3mg (0.5mmol) of iodone iodide, Xantphos (289.3mg (0.5mmol) of CAS:161265-03-8), and 32.6g (100mmol) of cesium carbonate were dissolved in 200mL of N, N-dimethylformamide. Heated to 60 ℃ and stirred for 16 h. The reaction was terminated by Thin Layer Chromatography (TLC) and quenched by adding 200mL of distilled water to the system. Ethyl acetate (200mL × 2) was extracted, and the organic phase was washed with saturated brine (200mL × 2). The mixture was dried over anhydrous magnesium sulfate, rotary evaporated to dryness and separated by column chromatography to give 10.47g (yield 94%) of a yellow solid powder. And (3) performing hydrogen spectrum nuclear magnetic resonance characterization on the product, wherein the spectrogram is shown in figure 1, and the nuclear magnetic peak data is as follows:
1H NMR(CDCl3,400MHz):δ8.23(d,J＝8.84Hz,2H),7.67(d,J＝8.88Hz,2H),7.58-7.55(m,2H),7.40-7.39(m,3H)。
step 2: synthesis of 4-nitrobenzoyl
8.9g (40mmol) of 1-nitro-4-phenylacetylene benzene was uniformly dissolved in 250mL of dimethyl sulfoxide, and 709.3mg (4mmol) of palladium dichloride was further added. Heated to 145 ℃ and stirred for 4 h. The reaction was terminated by Thin Layer Chromatography (TLC) and quenched by adding 250mL of distilled water to the system. Ethyl acetate (150ml x 2) was extracted and the organic phase was washed with saturated brine (100ml x 2). The extract was dried over anhydrous magnesium sulfate, rotary evaporated to dryness and separated by column chromatography to give 8.78g (yield: 86%) of a yellow solid powder. And (3) performing hydrogen nuclear magnetic resonance characterization on the product, wherein the spectrogram is shown in figure 2, and the nuclear magnetic peak data is as follows:
1H NMR(CDCl3,400MHz):δ8.36(d,J＝8.28Hz,2H),8.17(d,J＝7.72Hz,2H),7.99(d,J＝7.28Hz,2H),7.73-7.70(m,1H),7.58-7.54(m,2H)。
and step 3: synthesis of 2- (4-nitrophenyl) -3-phenyl-6-nitroquinoxaline and 3- (4-nitrophenyl) -2-phenyl-6-nitroquinoxaline mixtures
6.7g (26mmol) of 4-nitrobenzoyl, 4.0g (26mmol) of 4-nitrophthalenediamine and 241mg (1.3mmol) of saccharin were uniformly dissolved in 250mL of glacial acetic acid at ordinary temperature and pressure. Stir at room temperature for 1 h. The reaction was terminated by Thin Layer Chromatography (TLC) and quenched by adding 250mL of distilled water to the system. Filtration, washing with distilled water three times, and drying gave 9.49g (yield 98%) of a yellow solid powder. The product was characterized by hydrogen nuclear magnetic resonance (including a mixture of two isomers) as shown in fig. 3, and the nuclear magnetic peak data were as follows:
1H NMR(CDCl3,400MHz):δ9.10(1H),8.59-8.56(1H),8.34-8.32(1H),8.24-8.22(2H),7.78-7.75(2H),7.54-7.39(5H)。
and 4, step 4: synthesis of 2- (4-aminophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-aminophenyl) -2-phenyl-6-aminoquinoxaline mixtures
9g (24mmol) of the nitro mixture was dissolved homogeneously in 250mL of methanol and 0.9g of 5% palladium on carbon was added. The solution was placed in a hydrogen bag to replace hydrogen three times and stirred at room temperature under one atmosphere for 12 hours. The reaction was monitored by Thin Layer Chromatography (TLC) for completion, filtered through celite, and the palladium on carbon was recovered. The filtrate was concentrated and recrystallized from methanol to obtain 5.85g (yield: 78%) of a yellow solid powder. The product was characterized by hydrogen nuclear magnetic resonance (including a mixture of two isomers) as shown in fig. 4, and the nuclear magnetic peak data were as follows:
1H NMR(DMSO-d6,500MHz):δ7.74-7.71(1H),7.45-7.41(2H),7.37-7.33(3H),7.23-7.16(1H),7.12-7.06(2H),6.94-6.92(1H),6.47-6.44(2H),6.02-5.98(2H),5.36-5.27(2H)。
the embodiments described above are intended to facilitate the understanding and appreciation of the application by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present application is not limited to the embodiments herein, and those skilled in the art who have the benefit of this disclosure will appreciate that many modifications and variations are possible within the scope of the present application without departing from the scope and spirit of the present application.

Claims (10)

1. A method for synthesizing nitroquinoxaline or a derivative thereof, comprising the steps of: reacting a mononitro-substituted o-phenylenediamine or derivative thereof with a mononitro-substituted benzil or derivative thereof in a solvent in the presence of a catalyst, o-benzoylsulfimide, for a predetermined period of time to obtain said nitroquinoxaline or derivative thereof;
wherein the mononitro-substituted o-phenylenediamine or derivative thereof has a structure represented by the following general formula (I):
in formula (I), the groups R1, R2, R3 and R4 are each independently selected from H, C1-C10 alkyl or nitro, and only one and one of the groups R1, R2, R3 and R4 is nitro;
wherein the mononitro-substituted benzil has a structure represented by the following general formula (II):
in general formula (II), the groups R5, R6, R7, R8, R9, R10, R11, R12, R13 and R14 are each independently selected from H, C1-C10 alkyl or nitro, and one and only one of the groups R5, R6, R7, R8, R9, R10, R11, R12, R13 and R14 is nitro;
wherein the nitroquinoxaline or the derivative thereof has a structure represented by the following general formula (III):
in formula (III), the groups R21, R22, R23 and R24 are each independently selected from H, C1-C10 alkyl or nitro, and one and only one of the groups R21, R22, R23 and R24 is nitro; in general formula (III), the groups R31, R32, R33, R34, R35, R41, R42, R43, R44 and R45 are each independently selected from H, C1-C10 alkyl or nitro, and one and only one of the groups R31, R32, R33, R34, R35, R41, R42, R43, R44 and R45 is nitro.
2. The method for synthesizing nitroquinoxaline or a derivative thereof according to claim 1, wherein the mononitro-substituted benzil or a derivative thereof comprises 4-nitrobenzoyl, 3-nitrobenzoyl, 2-methyl-4-nitrobenzoyl, 3-methyl-4-nitrobenzoyl, 2, 3-dimethyl-4-nitrobenzoyl, 2,3, 5-trimethyl-4-nitrobenzoyl;
and/or the mononitro-substituted o-phenylenediamine or the derivative thereof is 3-nitrophthalenediamine, 4-nitrophthalenediamine, 5-nitrophthalenediamine, 6-nitrophthalenediamine, 3-methyl-4-nitrophthalenediamine, 5-methyl-4-nitrophthalenediamine, 3, 5-dimethyl-4-nitrophthalenediamine or 3,5, 6-trimethyl-4-nitrophthalenediamine;
and/or the solvent is one or more of glacial acetic acid, methanol, N N-dimethylformamide or acetonitrile.
3. The method for synthesizing nitroquinoxaline or a derivative thereof according to claim 1, wherein the catalyst o-benzoylsulfimide is used in an amount of 5% or less based on the molar ratio to the mono-nitro substituted benzil.
4. The method for synthesizing a nitroquinoxaline or a derivative thereof according to claim 1, wherein the nitroquinoxaline or the derivative thereof comprises a mixture of 2- (4-nitrophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-nitrophenyl) -2-phenyl-6-aminoquinoxaline.
5. The method for synthesizing nitroquinoxaline or a derivative thereof according to claim 2, wherein the 4-nitrobenzoyl group is prepared by the following method:
(1) reacting nitrohalogenated benzene with phenylacetylene to obtain 1-nitro-4-phenylacetylene; and
(2) reacting 1-nitro-4-phenylacetylene with an oxidant in the presence of a metal catalyst to obtain the 4-nitrobenzoyl.
6. The method for synthesizing nitroquinoxaline or a derivative thereof according to claim 5, wherein the nitrohalogenobenzene is 4-nitroiodobenzene, 4-nitrobromobenzene or 4-nitrochlorobenzene;
and/or the metal catalyst is palladium dichloride or a mixture of aluminum chloride and palladium acetate in equimolar amount;
and/or the oxidizing agent is dimethyl sulfoxide.
7. A method for synthesizing an aminoquinoxaline or a derivative thereof, which comprises reducing a nitro group corresponding to the nitroquinoxaline or the derivative thereof prepared by the method for synthesizing a nitroquinoxaline or the derivative thereof according to claim 1 to an amino group to obtain the aminoquinoxaline or the derivative thereof.
8. The method for synthesizing aminoquinoxaline or a derivative thereof according to claim 7, wherein the aminoquinoxaline or the derivative thereof is a mixture of 2- (4-aminophenyl) -3-phenyl-6-aminoquinoxaline and 3- (4-aminophenyl) -2-phenyl-6-aminoquinoxaline.
9. An application of o-benzoyl sulfonyl imide as a catalyst in synthesizing nitroquinoxaline or derivatives thereof.
10. A process for preparing 4-nitrobenzoyl comprising the steps of:
(1) reacting nitrohalogenated benzene with phenylacetylene to obtain 1-nitro-4-phenylacetylene; and
(2) reacting 1-nitro-4-phenylacetylene with an oxidant in the presence of a metal catalyst to obtain the 4-nitrobenzoyl.
CN201910966508.XA 2019-10-12 2019-10-12 Method for synthesizing nitroquinoxaline or derivative thereof and aminoquinoxaline or derivative thereof Pending CN110627732A (en)

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