CN110292948A - Imidazoles villaumite containing single imines functionalization is preparing the application in aromatic heterocycle formic ether compounds as catalyst - Google Patents

Imidazoles villaumite containing single imines functionalization is preparing the application in aromatic heterocycle formic ether compounds as catalyst Download PDF

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CN110292948A
CN110292948A CN201910395225.4A CN201910395225A CN110292948A CN 110292948 A CN110292948 A CN 110292948A CN 201910395225 A CN201910395225 A CN 201910395225A CN 110292948 A CN110292948 A CN 110292948A
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catalyst
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aromatic heterocycle
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CN110292948B (en
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孙宏枚
刘灵
朱凡
周巧云
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Suzhou 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
    • B01J31/0235—Nitrogen containing compounds
    • B01J31/0244—Nitrogen containing compounds with nitrogen contained as ring member in aromatic compounds or moieties, e.g. pyridine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • 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
    • B01J2231/49—Esterification or transesterification

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  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

The invention discloses a kind of methods for synthesizing aromatic heterocycle formic ether compounds, i.e., with molecular formula for [(ArN=C (CH3)NCH2CH2NCH2C6H5) CH] and Cl imidazoles villaumite (wherein bis--CH (CH of Ar=2,6-3)2‑C6H3) it is catalyst, aromatic heterocycle formic ether compounds are synthesized by the carboxylation reaction of heteroaromatic compound and carbon dioxide under normal pressure.This is the first case that aromatic heterocycle formic ether compounds are prepared by the carboxylation reaction of heteroaromatic compound and carbon dioxide being catalyzed by imidazole salts, compared with prior art, not only catalyst is more green, synthesis is easier, and reaction condition is mild, has suitable or better catalytic activity and functional group's tolerance.

Description

Imidazoles villaumite containing single imines functionalization is preparing aromatic heterocycle formic acid as catalyst Application in ester type compound
The present invention be it is entitled it is a kind of synthesize aromatic heterocycle formic ether compounds method, application No. is 2016109319327, the applying date is the divisional application of the October in 2016 of patent application on the 31st, belongs to catalyst Division Of Applied Technology Point.
Technical field
The invention belongs to the field of chemical synthesis, and in particular to utilizing the imidazoles villaumite containing single imines functionalization is catalyst conjunction At the method for aromatic heterocycle formic ether compounds.
Background technique
Aromatic heterocycle formic ether compounds are raw material or intermediate and natural products, agriculture important in organic synthesis Important skeleton in medicine or medicine.In recent years, using carbon dioxide as the source C1, pass through the carboxylation reaction of heteroaromatic compound Method to prepare aromatic heterocycle formic ether compounds, is rapidly developed.
2010, Nolan et al. discovery aza ring carbene complex of golden (I) in the presence of room temperature and potassium hydroxide can urge The carboxylation reaction for changing heteroaromatic compound and carbon dioxide (1.4 atmospheric pressure), can be used for aromatic heterocycle formate ester Close the synthesis of object；Then, the aza ring carbene complex which reports similar copper (I) is deposited in 40 DEG C and cesium hydroxide Under, it can also be catalyzed the carboxylation reaction of heteroaromatic compound and carbon dioxide (1.4 atmospheric pressure)；At the same time, Hou Zhao People et al. in the presence of 80 DEG C and potassium tert-butoxide, synthesize this kind of compound using the aza ring carbene complex of similar copper (I) (referring to: I. I. F. Boogaerts, S. P. Nolan,J. Am. Chem. Soc., 2010, 132, 8858- 8859;I. I. F. Boogaerts, G. C. Fortman, M. R. L. Furst, C. S. J. Cazin, S. P. Nolan, Angew. Chem. Int. Ed., 2010, 49, 8674-8677;L. Zhang, J. Cheng, T. Ohishi, Z. Hou, Angew. Chem. Int. Ed, 2010,49,8670-8673).
The prior art can be realized aromatic heterocycle formate ester chemical combination using metal active using transition-metal catalyst The synthesis of object, but golden series catalysts are expensive, and Cu-series catalyst has toxicity, most of dioxy for also needing certain pressure again Change carbon, answers factor there are dangerous.Up to the present, it yet there are no using the imidazoles villaumite of single imines functionalization as catalyst, pass through The carboxylation reaction of heteroaromatic compound and carbon dioxide under normal pressure synthesizes the reports of aromatic heterocycle formic ether compounds Road.
Summary of the invention
The purpose of the present invention is to provide a kind of methods for synthesizing aromatic heterocycle formic ether compounds, i.e., are with molecular formula [(ArN=C(CH3)NCH2CH2NCH2C6H5) CH] and Cl imidazoles villaumite (wherein bis--CH (CH of Ar=2,6-3)2-C6H3) it is catalysis Agent synthesizes virtue by the carboxylation reaction of heteroaromatic compound and carbon dioxide under normal pressure in the presence of potassium tert-butoxide Fragrant heterocyclic formic ester type compound.
In order to achieve the above objectives, the technical solution adopted by the present invention is that: a kind of synthesis aromatic heterocycle formic ether compounds Method, include the following steps, in an inert gas atmosphere, using the imidazoles villaumite containing single imines functionalization as catalyst, with virtue Fragrant heterocyclic compound and carbon dioxide are raw material, in the presence of a base, carry out synthesis under normal pressure；Halogenated hydrocarbons, ester are added after reaction Change reaction and obtains aromatic heterocycle formic ether compounds；The chemical structural formula of the imidazoles villaumite containing single imines functionalization is such as Under:
。
In above-mentioned technical proposal, heteroaromatic compound be benzoxazoles class compound, benzothiazole compound or Benzimidazoles compound；The method of the present invention substrate applicability is excellent, not only can using conventional heteroaromatic compound as raw material, It can also be catalyzed the substrate of more difficult reaction, such as benzimidazoles compound, benzothiazole compound, thus the more knots of preparation The aromatic heterocycle formic ether compounds of structure.
In above-mentioned technical proposal, synthesis under normal pressure temperature is 50~85 DEG C, and the time is 12~24 hours；Esterification reaction temperature is 45~75 DEG C, the time is 0.5~2 hour.
In above-mentioned technical proposal, reaction carries out in organic solvent, such asN,NDimethylformamide (DMF) orN,N- two Methylacetamide (DMA), preferably DMF, can good dissolution reaction raw materials so that reaction is uniform.
In above-mentioned technical proposal, halogenated hydrocarbons is idohydrocarbon, preferably iodomethane, and iodomethane is good O- methylating reagent, Esterification can be made to go on smoothly.
In above-mentioned technical proposal, using the imidazoles villaumite containing single imines functionalization as single component catalyst, potassium tert-butoxide or In the presence of person's cesium carbonate is as alkali, virtue is synthesized by the carboxylation reaction of heteroaromatic compound and carbon dioxide under normal pressure Fragrant heterocyclic formic ester type compound, specifically includes the following steps: in an inert gas atmosphere, successively by catalyst, alkali, solvent, Heteroaromatic compound is added in reaction flask；Then pass to carbon dioxide gas；At 50~85 DEG C, it is stirred to react under normal pressure 12~24 hours；Then halogenated hydrocarbons is added, esterification obtains aromatic heterocycle formic ether compounds.
In above-mentioned technical proposal, after esterification, is terminated and reacted with deionized water after reaction solution is cooling, then use acetic acid Ethyl ester extraction, obtains aromatic heterocycle formic ether compounds finally by column Image processing.
In above-mentioned technical proposal, in molar ratio, the amount ranges of catalyst are the 1%~5% of heteroaromatic compound, alkali Amount ranges are 1.0~1.5 times of heteroaromatic compound.
In preferred technical solution, when heteroaromatic compound is benzoxazoles class compound, with the meter of substance, alkali Dosage be 1.2 times of benzoxazoles class compound, the dosage of catalyst is 5 % of benzoxazoles class compound, halogenated hydrocarbons Dosage is 3.0 times of benzoxazoles class compound；Synthesis under normal pressure temperature is 80 DEG C, and the time is 18 hours；Esterification reaction temperature is 65 DEG C, the time is 1 hour.
The invention also discloses the imidazoles villaumite containing single imines functionalization as catalyst in catalysis heteroaromatic compound With the application in carbon dioxide reaction；And the imidazoles villaumite containing single imines functionalization is preparing aromatic heterocycle first as catalyst Application in acid esters compound.
Due to the above technical solutions, the present invention has the following advantages over the prior art:
1. the present invention avoids the use of metallic catalyst for the first time, uses the imidazoles villaumite of single imines functionalization for catalyst, have Feature cheap and easy to get, green environment is friendly, stable in the air is conducive to synthesize use on a large scale.
2. reaction carries out under normal pressure, has in the method for synthesis aromatic heterocycle formic ether compounds disclosed by the invention Effect guarantees safety, overcomes the prior art and thinks to need certain pressure, such as the problem of 1.4 atmospheric pressure ability effecting reaction, The product gas phase yield of preparation reaches 95%, achieves unexpected technical effect.
3. it is disclosed by the invention synthesis aromatic heterocycle formic ether compounds method in, synthesis under normal pressure temperature be 50~ 85 DEG C, preferably 65~80 DEG C, most preferably 80 DEG C；Under the prior art thinks that no metal participates in, heteroaromatic compound and titanium dioxide The carboxylation reaction of carbon, effective temperature cannot then convert (yield is lower than 80%) at least at 100 DEG C, lower than 100 DEG C even not very well (without product at 65 DEG C) can be converted, reaction yield can be up to 95% at 80 DEG C using technical method of the invention, or even at 65 DEG C Lower reaction yield achieves unexpected technical effect up to 72%.
4. preparation method disclosed by the invention has universality to a variety of reaction substrates, can not only efficient catalytic benzo The carboxylation reaction of oxazole class heteroaromatic compound, for the benzothiazole compound that cannot achieve with the prior art Carboxylation reaction can smoothly realize that substrate universality and product yield have bright compared with prior art using method of the invention It is aobvious to improve.
Specific embodiment
The present invention will be further described below with reference to examples:
In the present embodiment, imidazoles villaumite molecular formula of the catalyst containing single imines functionalization is [(ArN=C (CH3) NCH2CH2NCH2C6H5) CH] Cl(wherein bis--CH (CH of Ar=2,6-3)2-C6H3), chemical structural formula is as follows:
。
The carboxylation reaction of one benzoxazoles of embodiment and carbon dioxide synthesizes benzoxazoles -2- methyl formate
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), benzoxazoles (50.7 microlitres, 0.5 mM) is passed through carbon dioxide gas Body, lower 80 DEG C of normal pressure are stirred to react 18 hours.65 DEG C are cooled to, is added iodomethane (93 microlitres, 1.5 mMs), 65 DEG C of stirrings Reaction 1 hour.It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, through gas chromatographic analysis Yield is 95%, column Chromatographic purification (using ethyl acetate/petroleum ether volume ratio be 1: 10 mixed solvent as solvent), yield is 90%。
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), tertiary fourth are sequentially added under argon gas protection Potassium alcoholate (0.056 gram, 0.5 mM), DMF(3.0 milliliters), benzoxazoles (50.7 microlitres, 0.5 mM) is passed through titanium dioxide Carbon gas, lower 80 DEG C of normal pressure are stirred to react 18 hours.65 DEG C are cooled to, is added iodomethane (93 microlitres, 1.5 mMs), 65 DEG C It is stirred to react 1 hour.It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, column Chromatographic purification (using ethyl acetate/petroleum ether volume ratio be 1: 10 mixed solvent as solvent), yield 88%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 7.87 (d, J = 7.6 Hz, 1H), 7.64 (d, J = 8.2 Hz, 1H), 7.51 (dd, J 1 = 7.6 Hz, J 2 = 1.5 Hz, 1H), 7.44 (m, 1H), 4.07 (s, 3H)。
The carboxylation reaction of embodiment dibenzo oxazole and carbon dioxide synthesizes benzoxazoles -2- Ethyl formate
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), benzoxazoles (50.7 microlitres, 0.5 mM) is passed through carbon dioxide gas Body, lower 80 DEG C of normal pressure are stirred to react 18 hours.65 DEG C are cooled to, is added iodoethane (120 microlitres, 1.5 mMs), 65 DEG C of stirrings Reaction 1 hour.It being cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, column Chromatographic purification (with The mixed solvent that ethyl acetate/petroleum ether volume ratio is 1: 10 is solvent), yield 89%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 7.90 (d, J = 7.6 Hz, 1H), 7.67 (d, J = 8.2 Hz, 1H ), 7.55 (dd, J 1 = 7.6 Hz, J 2 = 1.5 Hz, 1H), 7.44 (m, 1H), 4.57 (q, J = 7.1 Hz, 2H), 1.50 (t, J = 7.1 Hz, 3H)。
The carboxylation reaction of three benzoxazoles of embodiment and carbon dioxide synthesizes benzoxazoles -2- hexyl formate
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), benzoxazoles (50.7 microlitres, 0.5 mM) is passed through carbon dioxide gas Body, lower 80 DEG C of normal pressure are stirred to react 18 hours.65 DEG C are cooled to, is added 1- iodohexane (222 microlitres, 1.5 mMs), 65 DEG C are stirred Mix reaction 1 hour.It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, column Chromatographic purification (using ethyl acetate/petroleum ether volume ratio be 1: 10 mixed solvent as solvent), yield 85%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 7.90 (d, J = 6.8Hz, 1H), 7.67 (d, J = 6.8Hz, 1H), 7.55 (dd, J 1 = 6.8 Hz, J 2 = 1.6 Hz, 1H), 7.44 (m, 1H), 4.38 (t, J = 6.8Hz, 2H), 1.70-1.79 (m, 2 H), 1.21-1.38 (m, 6H), 0.79 (t, J = 6.6Hz, 3H)。
The carboxylation reaction of example IV benzoxazoles and carbon dioxide synthesizes benzoxazoles -2- methyl formate
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), benzoxazoles (50.7 microlitres, 0.5 mM) is passed through carbon dioxide gas Body, lower 65 DEG C of normal pressure are stirred to react 18 hours.It is added iodomethane (93 microlitres, 1.5 mMs), 65 DEG C are stirred to react 1 hour. It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, and column Chromatographic purification is (with ethyl acetate/stone The mixed solvent that oily ether volume ratio is 1: 10 is solvent), yield 72%.
In reaction flask, catalyst (2.0 milligrams, 0.005 mM, 1 mol%), tertiary fourth are sequentially added under argon gas protection Potassium alcoholate (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), benzoxazoles (50.7 microlitres, 0.5 mM) is passed through titanium dioxide Carbon gas, lower 80 DEG C of normal pressure are stirred to react 18 hours.65 DEG C are cooled to, is added iodomethane (93 microlitres, 1.5 mMs), 65 DEG C It is stirred to react 1 hour.It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, column Chromatographic purification (using ethyl acetate/petroleum ether volume ratio be 1: 10 mixed solvent as solvent), yield 70%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 7.87 (d, J = 7.6 Hz, 1H), 7.64 (d, J = 8.2 Hz, 1H), 7.51 (dd, J 1 = 7.6 Hz, J 2 = 1.5 Hz, 1H), 7.44 (m, 1H), 4.07 (s, 3H)。
The carboxylation reaction of five benzoxazoles of embodiment and carbon dioxide synthesizes benzoxazoles -2- methyl formate
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), benzoxazoles (50.7 microlitres, 0.5 mM) is passed through carbon dioxide gas Body, lower 50 DEG C of normal pressure are stirred to react 18 hours.It is added iodomethane (93 microlitres, 1.5 mMs), 65 DEG C are stirred to react 1 hour. It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, and column Chromatographic purification is (with ethyl acetate/stone The mixed solvent that oily ether volume ratio is 1: 10 is solvent), yield 54%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 7.87 (d, J = 7.6 Hz, 1H), 7.64 (d, J = 8.2 Hz, 1H), 7.51 (dd, J 1 = 7.6 Hz, J 2 = 1.5 Hz, 1H), 7.44 (m, 1H), 4.07 (s, 3H)。
The carboxylation reaction of six benzoxazoles of embodiment and carbon dioxide synthesizes benzoxazoles -2- methyl formate
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), cesium carbonate are sequentially added under argon gas protection (0.1955 gram, 0.6 mM), DMF(3.0 milliliters), benzoxazoles (50.7 microlitres, 0.5 mM) is passed through carbon dioxide gas Body, lower 80 DEG C of normal pressure are stirred to react 18 hours.65 DEG C are cooled to, is added iodomethane (93 microlitres, 1.5 mMs), 65 DEG C of stirrings Reaction 1 hour.It being cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, column Chromatographic purification (with The mixed solvent that ethyl acetate/petroleum ether volume ratio is 1: 10 is solvent), yield 60%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 7.87 (d, J = 7.6 Hz, 1H), 7.64 (d, J = 8.2 Hz, 1H), 7.51 (dd, J 1 = 7.6 Hz, J 2 = 1.5 Hz, 1H), 7.44 (m, 1H), 4.07 (s, 3H)。
The carboxylation reaction of seven 5- bromine benzoxazoles of embodiment and carbon dioxide synthesizes 5- bromine benzoxazoles -2- formic acid first Ester
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), 5- bromine benzoxazoles (99.01 milligrams, 0.5 mM) is passed through dioxy Change carbon gas, lower 80 DEG C of normal pressure are stirred to react 18 hours.65 DEG C are cooled to, is added iodomethane (93 microlitres, 1.5 mMs), 65 It DEG C is stirred to react 1 hour.It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, and column chromatography mentions It is pure (using ethyl acetate/petroleum ether volume ratio be 1: 10 mixed solvent as solvent), yield 85%.
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), tertiary fourth are sequentially added under argon gas protection Potassium alcoholate (0.084 gram, 0.75 mM), DMF(3.0 milliliters), 5- bromine benzoxazoles (99.01 milligrams, 0.5 mM) is passed through Carbon dioxide gas, lower 80 DEG C of normal pressure are stirred to react 18 hours.Be cooled to 65 DEG C, be added iodomethane (93 microlitres, 1.5 mmoles You), 65 DEG C are stirred to react 1 hour.It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, column Chromatographic purification (using ethyl acetate/petroleum ether volume ratio be 1: 10 mixed solvent as solvent), yield 88%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 8.02 (d, J = 1.6 Hz, 1H), 7.55 (m, 1H), 7.62 (dd, J1 = 8.8 Hz, J2 = 1.6 Hz, 1H), 4.09 (s, 3H)。
The carboxylation reaction of eight 5- chlorobenzene diozaiole of embodiment and carbon dioxide synthesizes 5- chlorobenzene diozaiole -2- formic acid first Ester
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), 5- chlorobenzene diozaiole (76.79 milligrams, 0.5 mM) is passed through dioxy Change carbon gas, lower 80 DEG C of normal pressure are stirred to react 18 hours.65 DEG C are cooled to, is added iodomethane (93 microlitres, 1.5 mMs), 65 It DEG C is stirred to react 1 hour.It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, and column chromatography mentions It is pure (using ethyl acetate/petroleum ether volume ratio be 1: 10 mixed solvent as solvent), yield 82%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 7.83 (d, J = 2.1 Hz, 1H), 7.57 (m, 1H), 7.47 (dd, J1 = 8.8 Hz, J2 = 2.1 Hz, 1H), 4.07 (s, 3H)。
The carboxylation reaction of nine 5- methylbenzoxazole of embodiment and carbon dioxide synthesizes 5- methylbenzoxazole -2- first Sour methyl esters
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), 5- methylbenzoxazole (66.58 milligrams, 0.5 mM) is passed through two Carbon oxide gas, lower 80 DEG C of normal pressure are stirred to react 18 hours.65 DEG C are cooled to, is added iodomethane (93 microlitres, 1.5 mMs), 65 DEG C are stirred to react 1 hour.It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, column chromatography Purification (using ethyl acetate/petroleum ether volume ratio be 1: 10 mixed solvent as solvent), yield 88%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 7.65 (s, 1H), 7.52 (d, J = 8.8Hz, 1H), 7.35 (d,J = 8.4 Hz, 1H), 4.09 (s, 3H), 2.50 (s, 3H)。
The carboxylation reaction of ten 6- methylbenzoxazole of embodiment and carbon dioxide synthesizes 6- methylbenzoxazole -2- first Sour methyl esters
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), 6- methylbenzoxazole (58.0 microlitres, 0.5 mM) is passed through dioxy Change carbon gas, lower 80 DEG C of normal pressure are stirred to react 18 hours.65 DEG C are cooled to, is added iodomethane (93 microlitres, 1.5 mMs), 65 It DEG C is stirred to react 1 hour.It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, and column chromatography mentions It is pure (using ethyl acetate/petroleum ether volume ratio be 1: 10 mixed solvent as solvent), yield 84%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 7.74 (d, J = 8.4 Hz, 1H), 7.45(s, 1H), 7.29 (d,J = 10.0 Hz, 1H), 4.08 (s, 3H), 2.53 (s, 3H)。
The carboxylation reaction of 11 benzothiazole of embodiment and carbon dioxide synthesizes benzothiazole -2- methyl formate
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), benzothiazole (55.0 microlitres, 0.5 mM) is passed through carbon dioxide gas Body, lower 80 DEG C of normal pressure are stirred to react 18 hours.65 DEG C are cooled to, is added iodomethane (93 microlitres, 1.5 mMs), 65 DEG C of stirrings Reaction 1 hour.It being cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, column Chromatographic purification (with The mixed solvent that ethyl acetate/petroleum ether volume ratio is 1: 10 is solvent), yield 89%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 8.20 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.52 (m, 2H), 4.05 (s, 3H)。
The carboxylation reaction of ten bisbenzothiazole of embodiment and carbon dioxide synthesizes benzothiazole -2- methyl formate
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), benzothiazole (55.0 microlitres, 0.5 mM) is passed through carbon dioxide gas Body, lower 65 DEG C of normal pressure are stirred to react 18 hours.It is added iodomethane (93 microlitres, 1.5 mMs), 65 DEG C are stirred to react 1 hour.It is cold But it to room temperature, is terminated and is reacted with deionized water, reaction product is extracted with ethyl acetate, and column Chromatographic purification is (with ethyl acetate/petroleum The mixed solvent that ether volume ratio is 1: 10 is solvent), yield 52%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 8.20 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.52 (m, 2H), 4.05 (s, 3H)。
The carboxylation reaction of 13 benzothiazole of embodiment and carbon dioxide synthesizes benzothiazole -2- hexyl formate
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), benzothiazole (55.0 microlitres, 0.5 mM) is passed through carbon dioxide gas Body, lower 80 DEG C of normal pressure are stirred to react 18 hours.65 DEG C are cooled to, is added 1- iodohexane (222 microlitres, 1.5 mMs), 65 DEG C are stirred Mix reaction 1 hour.It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, column Chromatographic purification (using ethyl acetate/petroleum ether volume ratio be 1: 10 mixed solvent as solvent), yield 80%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 8.20 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 8.4 Hz, 1H), 7.52 (m, 2H), 4.05 (q, J = 7.1 Hz, 2H), 1.31 (t, J = 7.1 Hz, 3H)。
The carboxylation reaction of 14 6- methoxybenzothiazole of embodiment and carbon dioxide synthesizes 6- methoxyl group benzo thiophene Azoles -2- methyl formate
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), 6- methoxybenzothiazole (82.5 milligrams, 0.5 mM) is passed through two Carbon oxide gas, lower 80 DEG C of normal pressure are stirred to react 18 hours.65 DEG C are cooled to, is added iodomethane (93 microlitres, 1.5 mMs), 65 DEG C are stirred to react 1 hour.It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, column chromatography Purification (using ethyl acetate/petroleum ether volume ratio be 1: 10 mixed solvent as solvent), yield 82%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 8.11 (d, J = 8.8 Hz, 1H), 7.36 (s, 1H), 7.18 (dd, J 1= 8.8 Hz, J 2 = 2.4 Hz, 1H), 4.06 (s, 3H), 3.90 (s, 3H)。
The carboxylation reaction of 15 6- chloro benzothiazole of embodiment and carbon dioxide synthesizes 6- chloro benzothiazole -2- formic acid Methyl esters
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), 6- chloro benzothiazole (84.99 milligrams, 0.5 mM) is passed through dioxy Change carbon gas, lower 80 DEG C of normal pressure are stirred to react 18 hours.65 DEG C are cooled to, is added iodomethane (93 microlitres, 1.5 mMs), 65 It DEG C is stirred to react 1 hour.It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, and column chromatography mentions It is pure (using ethyl acetate/petroleum ether volume ratio be 1: 10 mixed solvent as solvent), yield 75%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 8.13 (s, 1H), 7.60 (d, J = 8.4 Hz, 1H), 7.56 (d, J = 8.4 Hz, 1H), 4.06 (s, 3H)。
The carboxylation reaction of 16 1- tolimidazole of embodiment and carbon dioxide synthesizes 1- tolimidazole -2- Methyl formate
In reaction flask, catalyst (9.9 milligrams, 0.025 mM, 5 mol%), potassium tert-butoxide are sequentially added under argon gas protection (0.0672 gram, 0.6 mM), DMF(3.0 milliliters), 1- tolimidazole (60.0 microlitres, 0.5 mM) is passed through dioxy Change carbon gas, lower 80 DEG C of normal pressure are stirred to react 24 hours.65 DEG C are cooled to, is added iodomethane (93 microlitres, 1.5 mMs), 65 It DEG C is stirred to react 1 hour.It is cooled to room temperature, is terminated and reacted with deionized water, reaction product is extracted with ethyl acetate, and column chromatography mentions It is pure (using ethyl acetate/petroleum ether volume ratio be 1: 10 mixed solvent as solvent), yield 50%.
Product is dissolved in CDCl3In (about 0.4 milliliter), tube sealing surveys on Unity Inova-400 type NMR instrument at room temperature Fixed characterization.1H NMR (400MHz, CDCl3): 7.78 (m, 1H), 7.61 (m, 1H), 7.33 (m, 1H), 7.32 (m, 1H), 4.00 (s, 3H), 3.88 (s, 3H)。

Claims (10)

1. the imidazoles villaumite containing single imines functionalization is preparing the application in aromatic heterocycle formic ether compounds as catalyst, It is characterized in that, using heteroaromatic compound and carbon dioxide as raw material when preparing aromatic heterocycle formic ether compounds；It is described The chemical structural formula of imidazoles villaumite containing single imines functionalization is as follows:
。
2. application according to claim 1, it is characterised in that: preparing aromatic heterocycle formic ether compounds includes following step Suddenly, in an inert gas atmosphere, using the imidazoles villaumite containing single imines functionalization as catalyst, with heteroaromatic compound and dioxy Change carbon is raw material, in the presence of a base, carries out synthesis under normal pressure；Halogenated hydrocarbons is added after reaction, esterification obtains aromatic heterocycle Formic ether compounds.
3. application according to claim 2, it is characterised in that: the synthesis under normal pressure temperature is 50~85 DEG C, the time 12 ~24 hours；Esterification reaction temperature is 45~75 DEG C, and the time is 0.5~2 hour.
4. application according to claim 3, it is characterised in that: synthesis under normal pressure temperature is 80 DEG C, and the time is 18 hours；Esterification Reaction temperature is 65 DEG C, and the time is 1 hour.
5. application according to claim 2, it is characterised in that: the halogenated hydrocarbons is idohydrocarbon；The alkali is potassium tert-butoxide Or cesium carbonate；The reaction carries out in organic solvent.
6. application according to claim 2, which is characterized in that specifically includes the following steps: in an inert gas atmosphere, according to It is secondary that catalyst, alkali, solvent, heteroaromatic compound are added in reaction flask；Then pass to carbon dioxide gas；In 50~85 At DEG C, it is stirred to react under normal pressure 12~24 hours；Then halogenated hydrocarbons is added, esterification obtains aromatic heterocycle formate ester chemical combination Object.
7. application according to claim 2, it is characterised in that: in molar ratio, the amount ranges of catalyst are aromatic heterocycles The 1%~5% of compound, the amount ranges of alkali are 1.0~1.5 times of heteroaromatic compound.
8. application according to claim 7, it is characterised in that: with the meter of substance, the dosage of alkali is heteroaromatic compounds 1.2 times of object, the dosage of catalyst are 5 % of heteroaromatic compound, and the dosage of halogenated hydrocarbons is the 3.0 of heteroaromatic compound Times.
9. application according to claim 1, it is characterised in that: the heteroaromatic compound include dislike azole compounds, Thiazole compound, glyoxaline compound.
10. application according to claim 9, it is characterised in that: the heteroaromatic compound includes disliking azole compounds.
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