CN106565623A - Method of synthesizing heteroaromatic formic ether compound - Google Patents
Method of synthesizing heteroaromatic formic ether compound Download PDFInfo
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- CN106565623A CN106565623A CN201610931932.7A CN201610931932A CN106565623A CN 106565623 A CN106565623 A CN 106565623A CN 201610931932 A CN201610931932 A CN 201610931932A CN 106565623 A CN106565623 A CN 106565623A
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- reaction
- compound
- aromatic heterocycle
- formic ether
- ether compounds
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- -1 heteroaromatic formic ether compound Chemical class 0.000 title claims abstract description 47
- 238000000034 method Methods 0.000 title claims abstract description 24
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 9
- 238000006243 chemical reaction Methods 0.000 claims abstract description 101
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims abstract description 75
- 239000003054 catalyst Substances 0.000 claims abstract description 40
- 239000001569 carbon dioxide Substances 0.000 claims abstract description 38
- 229910002092 carbon dioxide Inorganic materials 0.000 claims abstract description 38
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 33
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 31
- 150000002390 heteroarenes Chemical class 0.000 claims abstract description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 119
- 238000003756 stirring Methods 0.000 claims description 38
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims description 29
- 239000008367 deionised water Substances 0.000 claims description 21
- 229910021641 deionized water Inorganic materials 0.000 claims description 21
- 239000002904 solvent Substances 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- 238000004440 column chromatography Methods 0.000 claims description 20
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 19
- 150000001875 compounds Chemical class 0.000 claims description 14
- 150000002460 imidazoles Chemical class 0.000 claims description 14
- 238000007306 functionalization reaction Methods 0.000 claims description 13
- 150000002466 imines Chemical class 0.000 claims description 13
- 239000003513 alkali Substances 0.000 claims description 9
- 238000005886 esterification reaction Methods 0.000 claims description 9
- 150000008282 halocarbons Chemical class 0.000 claims description 8
- 230000032050 esterification Effects 0.000 claims description 5
- 239000002994 raw material Substances 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- 239000012298 atmosphere Substances 0.000 claims description 4
- 239000011261 inert gas Substances 0.000 claims description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 claims description 3
- 229910000024 caesium carbonate Inorganic materials 0.000 claims description 3
- 238000006555 catalytic reaction Methods 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 239000003205 fragrance Substances 0.000 claims 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 2
- 150000002916 oxazoles Chemical class 0.000 claims 1
- 238000006473 carboxylation reaction Methods 0.000 abstract description 27
- 230000003197 catalytic effect Effects 0.000 abstract description 2
- 150000003841 chloride salts Chemical class 0.000 abstract 1
- 125000000524 functional group Chemical group 0.000 abstract 1
- 150000004693 imidazolium salts Chemical class 0.000 abstract 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 64
- HEDRZPFGACZZDS-MICDWDOJSA-N deuterated chloroform Substances [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
- 239000007789 gas Substances 0.000 description 39
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 38
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 19
- 229910052786 argon Inorganic materials 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- 239000012046 mixed solvent Substances 0.000 description 19
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 18
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 18
- IOJUPLGTWVMSFF-UHFFFAOYSA-N cyclobenzothiazole Natural products C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 17
- 238000005160 1H NMR spectroscopy Methods 0.000 description 16
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- 239000003208 petroleum Substances 0.000 description 16
- 238000007789 sealing Methods 0.000 description 16
- 238000000746 purification Methods 0.000 description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 150000000183 1,3-benzoxazoles Chemical class 0.000 description 6
- 241000790917 Dioxys <bee> Species 0.000 description 6
- 239000005489 Bromoxynil Substances 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- ANOOTOPTCJRUPK-UHFFFAOYSA-N 1-iodohexane Chemical class CCCCCCI ANOOTOPTCJRUPK-UHFFFAOYSA-N 0.000 description 2
- VMQMZMRVKUZKQL-UHFFFAOYSA-N Cu+ Chemical compound [Cu+] VMQMZMRVKUZKQL-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- GCNLQHANGFOQKY-UHFFFAOYSA-N [C+4].[O-2].[O-2].[Ti+4] Chemical compound [C+4].[O-2].[O-2].[Ti+4] GCNLQHANGFOQKY-UHFFFAOYSA-N 0.000 description 2
- 229910002090 carbon oxide Inorganic materials 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000004575 stone Substances 0.000 description 2
- VKPJOERCBNIOLN-UHFFFAOYSA-N 1,3-benzoxazole-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=NC2=C1 VKPJOERCBNIOLN-UHFFFAOYSA-N 0.000 description 1
- MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 description 1
- PSCJODZIMUSFCK-UHFFFAOYSA-N 4,5-dihydro-1,3-oxazole-2-carboxylic acid Chemical compound OC(=O)C1=NCCO1 PSCJODZIMUSFCK-UHFFFAOYSA-N 0.000 description 1
- AIBQGOMAISTKSR-UHFFFAOYSA-N 6-chloro-1,3-benzothiazole Chemical class ClC1=CC=C2N=CSC2=C1 AIBQGOMAISTKSR-UHFFFAOYSA-N 0.000 description 1
- FXZTXJYJMOJSBU-UHFFFAOYSA-N 6-chloro-1,3-benzothiazole-2-carboxylic acid Chemical compound C1=C(Cl)C=C2SC(C(=O)O)=NC2=C1 FXZTXJYJMOJSBU-UHFFFAOYSA-N 0.000 description 1
- AHOIGFLSEXUWNV-UHFFFAOYSA-N 6-methoxy-1,3-benzothiazole Chemical class COC1=CC=C2N=CSC2=C1 AHOIGFLSEXUWNV-UHFFFAOYSA-N 0.000 description 1
- DWMDBTZBRQFLDO-UHFFFAOYSA-N COC=O.C(=O)=O Chemical compound COC=O.C(=O)=O DWMDBTZBRQFLDO-UHFFFAOYSA-N 0.000 description 1
- OHLUUHNLEMFGTQ-UHFFFAOYSA-N N-methylacetamide Chemical compound CNC(C)=O OHLUUHNLEMFGTQ-UHFFFAOYSA-N 0.000 description 1
- HUDZMKXIGQHGLG-UHFFFAOYSA-N O=C=O.C=1C=CNC=1 Chemical class O=C=O.C=1C=CNC=1 HUDZMKXIGQHGLG-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- 230000001035 methylating effect Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- 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 method of synthesizing a heteroaromatic formic ether compound. By taking midazolium chloride salt of which the molecular formula is [(ArN=C(CH3)NCH2CH2NCH2C6H5)CH]Cl (wherein Ar is equal to 2,6-bi-CH(CH3)2-C6H3) as a catalyst, the heteroaromatic formic ether compound is synthesized through carboxylation reaction of a heteroaromatic compound and carbon dioxide at atmospheric pressure. The heteroaromatic formic ether compound is a first example that is catalyzed by imidazolium salt and prepared through the carboxylation reaction of the heteroaromatic compound and carbon dioxide. Compared with the prior art, the catalyst is green, the synthesis is easier, reaction conditions are mild, and the heteroaromatic formic ether compound has equivalent or better catalytic activity and functional group tolerance.
Description
Technical field
The invention belongs to the field of chemical synthesis, and in particular to utilize the imidazoles villaumite containing single imines functionalization to be catalyst conjunction
Into the method for aromatic heterocycle formic ether compounds.
Background technology
Aromatic heterocycle formic ether compounds are raw materials or intermediate important in organic synthesis, are also natural products, agriculture
Important skeleton in medicine or medicine.In recent years, using carbon dioxide as C1 sources, by the carboxylation reaction of heteroaromatic compound
Method to prepare aromatic heterocycle formic ether compounds, has obtained rapid development.
2010, Nolan et al. had found that the aza ring carbene complex of in the presence of room temperature and potassium hydroxide golden (I) can be urged
Change heteroaromatic compound and carbon dioxide（1.4 atmospheric pressure）Carboxylation reaction, can be used for aromatic heterocycle formate ester
The synthesis of compound；Subsequently, the seminar reports the aza ring carbene complex of similar copper (I) and deposits in 40 DEG C and cesium hydroxide
Under, heteroaromatic compound and carbon dioxide can be also catalyzed（1.4 atmospheric pressure）Carboxylation reaction；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）.
Prior art uses transition-metal catalyst, using metal active, can realize aromatic heterocycle formate ester chemical combination
The synthesis of thing, but golden series catalysts are expensive, and Cu-series catalyst has toxicity again, and major part also needs to the dioxy of certain pressure
Change carbon, exist and dangerous answer factor.Up to the present, yet there are no with the imidazoles villaumite of single imines functionalization as catalyst, pass through
Heteroaromatic compound and carbon dioxide carboxylation reaction at ambient pressure is synthesizing the report of aromatic heterocycle formic ether compounds
Road.
The content of the invention
It is an object of the invention to provide a kind of method of synthesis aromatic heterocycle formic ether compounds, i.e., be with molecular formula
[(ArN=C(CH3)NCH2CH2NCH2C6H5) CH] and Cl imidazoles villaumite（Wherein-CH (the CH of Ar=2,6- bis-3)2-C6H3）For catalysis
Agent, in the presence of potassium tert-butoxide, by heteroaromatic compound and carbon dioxide carboxylation reaction at ambient pressure virtue is synthesized
Fragrant heterocyclic formic ester type compound.
To reach above-mentioned purpose, the technical solution used in the present invention is：One kind synthesis aromatic heterocycle formic ether compounds
Method, comprise the following steps, in inert gas atmosphere, with the imidazoles villaumite containing single imines functionalization as catalyst, with virtue
Fragrant heterocyclic compound is raw material with carbon dioxide, in the presence of a base, carries out synthesis under normal pressure；Reaction adds halogenated hydrocarbons, ester after terminating
Change reaction and obtain 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 Benzooxazole kind compound, benzothiazole compound or
Benzimidazoles compound；The inventive method substrate applicability is excellent, not only can with conventional heteroaromatic compound as raw material,
The substrate of more difficult reaction, such as benzimidazoles compound, benzothiazole compound can also be catalyzed, so as to prepare more knots
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 is carried out in organic solvent, such asN,N- dimethylformamide (DMF) orN,N- two
Methylacetamide (DMA), preferred DMF, dissolving reaction raw materials that can be good so that reaction is uniform.
In above-mentioned technical proposal, halogenated hydrocarbons is idohydrocarbon, preferred iodomethane, and iodomethane is good O- methylating reagents,
It is smoothed out esterification.
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 heteroaromatic compound and carbon dioxide carboxylation reaction at ambient pressure
Fragrant heterocyclic formic ester type compound, specifically includes following steps：In inert gas atmosphere, successively by catalyst, alkali, solvent,
Heteroaromatic compound is added in reaction bulb；Then pass to carbon dioxide；At 50～85 DEG C, stirring reaction under normal pressure
12～24 hours；Halogenated hydrocarbons is subsequently adding, esterification obtains aromatic heterocycle formic ether compounds.
In above-mentioned technical proposal, after esterification terminates, deionized water terminating reaction after reactant liquor cooling, then use acetic acid
Ethyl ester is extracted, and finally by column chromatography process aromatic heterocycle formic ether compounds are obtained.
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 scheme, when heteroaromatic compound is Benzooxazole kind compound, with the gauge of material, alkali
Consumption be 1.2 times of Benzooxazole kind compound, the consumption of catalyst for Benzooxazole kind compound 5 %, halogenated hydrocarbons
Consumption is 3.0 times of Benzooxazole kind 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 is being catalyzed heteroaromatic compound as catalyst
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.
Because above-mentioned technical proposal is used, the present invention has compared with prior art following advantages：
1. the present invention avoids first the use of metallic catalyst, adopts the imidazoles villaumite of single imines functionalization for catalyst, has
Cheap and easy to get, green environment is friendly, it is stable in the air the characteristics of, be conducive to extensive synthesis to use.
2. in the method for synthesis aromatic heterocycle formic ether compounds disclosed by the invention, reaction is carried out at ambient pressure, is had
Effect ensures security, overcomes prior art and thinks to need certain pressure, such as 1.4 atmospheric pressure could effecting reaction problem,
The product gas phase yield of preparation reaches 95%, achieves unexpected technique 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 prior art thinks to be participated in without metal, heteroaromatic compound and titanium dioxide
The carboxylation reaction of carbon, effective temperature at least at 100 DEG C, then can not be converted very well less than 100 DEG C（Yield is less than 80%）Not even
Can conversion（Without product at 65 DEG C）, reaction yield 95% can be up at 80 DEG C using the technical method of the present invention, or even at 65 DEG C
Lower reaction yield achieves unexpected technique effect up to 72%.
4. preparation method disclosed by the invention has universality to various reaction substrates, can not only efficient catalytic benzo
The carboxylation reaction of oxazole class heteroaromatic compound, for the benzothiazole compound that cannot be realized with prior art
Carboxylation reaction, can smoothly realize, compared to existing technology substrate universality and product yield have bright using the method for the present invention
It is aobvious to improve.
Specific embodiment
With reference to embodiment, the invention will be further described：
In the present embodiment, imidazoles villaumite molecular formula of the catalyst containing single imines functionalization is [(ArN=C (CH3)
NCH2CH2NCH2C6H5)CH]Cl（Wherein-CH (the CH of Ar=2,6- bis-3)2-C6H3）, chemical structural formula is as follows：
。
The carboxylation reaction synthesis benzoxazole -2- methyl formates of the benzoxazole of embodiment one and carbon dioxide
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, benzoxazole（50.7 microlitres, 0.5 mM）, it is passed through carbon dioxide gas
Body, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, iodomethane is added（93 microlitres, 1.5 mMs）, 65 DEG C of stirrings
Reaction 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, Jing gas chromatographic analysis
Yield is 95%, column chromatography purification（Mixed solvent with ethyl acetate/petroleum ether volume ratio as 1: 10 is as solvent）, yield is
90%。
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, tertiary fourth
Potassium alcoholate（0.056 gram, 0.5 mM）, DMF（3.0 milliliter）, benzoxazole（50.7 microlitres, 0.5 mM）, it is passed through titanium dioxide
Carbon gas, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, iodomethane is added（93 microlitres, 1.5 mMs）, 65 DEG C
Stirring reaction 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, column chromatography purification
（Mixed solvent with ethyl acetate/petroleum ether volume ratio as 1: 10 is as solvent）, yield is 88%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis benzoxazole -2- Ethyl formates of embodiment Er benzoxazole and carbon dioxide
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, benzoxazole（50.7 microlitres, 0.5 mM）, it is passed through carbon dioxide gas
Body, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, iodoethane is added（120 microlitres, 1.5 mMs）, 65 DEG C of stirrings
Reaction 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, column chromatography purification（With
Ethyl acetate/petroleum ether volume ratio is solvent for 1: 10 mixed solvent）, yield is 89%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis benzoxazole -2- hexyl formates of embodiment San benzoxazole and carbon dioxide
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, benzoxazole（50.7 microlitres, 0.5 mM）, it is passed through carbon dioxide gas
Body, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, 1- iodohexanes are added（222 microlitres, 1.5 mMs）, 65 DEG C are stirred
Mix reaction 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, column chromatography purification
（Mixed solvent with ethyl acetate/petroleum ether volume ratio as 1: 10 is as solvent）, yield is 85%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis benzoxazole -2- methyl formates of example IV benzoxazole and carbon dioxide
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, benzoxazole（50.7 microlitres, 0.5 mM）, it is passed through carbon dioxide gas
Body, the lower 65 DEG C of stirring reactions of normal pressure 18 hours.Add iodomethane（93 microlitres, 1.5 mMs）, 65 DEG C of stirring reactions 1 hour.
Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, column chromatography purification（With ethyl acetate/stone
Oily ether volume ratio is solvent for 1: 10 mixed solvent）, yield is 72%.
In reaction bulb, under argon gas protection catalyst is sequentially added（2.0 milligrams, 0.005 mM, 1 mol%）, tertiary fourth
Potassium alcoholate（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, benzoxazole（50.7 microlitres, 0.5 mM）, it is passed through titanium dioxide
Carbon gas, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, iodomethane is added（93 microlitres, 1.5 mMs）, 65 DEG C
Stirring reaction 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, column chromatography purification
（Mixed solvent with ethyl acetate/petroleum ether volume ratio as 1: 10 is as solvent）, yield is 70%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis benzoxazole -2- methyl formates of the benzoxazole of embodiment five and carbon dioxide
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, benzoxazole（50.7 microlitres, 0.5 mM）, it is passed through carbon dioxide gas
Body, the lower 50 DEG C of stirring reactions of normal pressure 18 hours.Add iodomethane（93 microlitres, 1.5 mMs）, 65 DEG C of stirring reactions 1 hour.
Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, column chromatography purification（With ethyl acetate/stone
Oily ether volume ratio is solvent for 1: 10 mixed solvent）, yield is 54%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis benzoxazole -2- methyl formates of embodiment Liu benzoxazole and carbon dioxide
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, cesium carbonate
（0.1955 gram, 0.6 mM）, DMF（3.0 milliliter）, benzoxazole（50.7 microlitres, 0.5 mM）, it is passed through carbon dioxide gas
Body, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, iodomethane is added（93 microlitres, 1.5 mMs）, 65 DEG C of stirrings
Reaction 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, column chromatography purification（With
Ethyl acetate/petroleum ether volume ratio is solvent for 1: 10 mixed solvent）, yield is 60%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis 5- bromoxynil oxazoline -2- formic acid first of the 5- bromoxynil oxazolines of embodiment seven and carbon dioxide
Ester
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, 5- bromoxynil oxazolines（99.01 milligrams, 0.5 mM）, it is passed through dioxy
Change carbon gas, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, iodomethane is added（93 microlitres, 1.5 mMs）, 65
DEG C stirring reaction 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, and column chromatography is carried
It is pure（Mixed solvent with ethyl acetate/petroleum ether volume ratio as 1: 10 is as solvent）, yield is 85%.
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, tertiary fourth
Potassium alcoholate（0.084 gram, 0.75 mM）, DMF（3.0 milliliter）, 5- bromoxynil oxazolines（99.01 milligrams, 0.5 mM）, it is passed through
Carbon dioxide, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, iodomethane is added（93 microlitres, 1.5 mmoles
You）, 65 DEG C of stirring reactions 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, post
Chromatographic purification（Mixed solvent with ethyl acetate/petroleum ether volume ratio as 1: 10 is as solvent）, yield is 88%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis 5- Lv benzoxazole -2- formic acid first of the 5- Lv benzoxazoles of embodiment eight and carbon dioxide
Ester
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, 5- Lv benzoxazoles（76.79 milligrams, 0.5 mM）, it is passed through dioxy
Change carbon gas, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, iodomethane is added（93 microlitres, 1.5 mMs）, 65
DEG C stirring reaction 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, and column chromatography is carried
It is pure（Mixed solvent with ethyl acetate/petroleum ether volume ratio as 1: 10 is as solvent）, yield is 82%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis 5- Jia base benzoxazole -2- first of the 5- Jia bases benzoxazoles of embodiment nine and carbon dioxide
Sour methyl esters
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, 5- Jia base benzoxazoles（66.58 milligrams, 0.5 mM）, it is passed through two
Carbon oxide gas, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, iodomethane is added（93 microlitres, 1.5 mMs）,
65 DEG C of stirring reactions 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, column chromatography
Purification（Mixed solvent with ethyl acetate/petroleum ether volume ratio as 1: 10 is as solvent）, yield is 88%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis 6- Jia base benzoxazole -2- first of the 6- Jia bases benzoxazoles of embodiment ten and carbon dioxide
Sour methyl esters
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, 6- Jia base benzoxazoles（58.0 microlitres, 0.5 mM）, it is passed through dioxy
Change carbon gas, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, iodomethane is added（93 microlitres, 1.5 mMs）, 65
DEG C stirring reaction 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, and column chromatography is carried
It is pure（Mixed solvent with ethyl acetate/petroleum ether volume ratio as 1: 10 is as solvent）, yield is 84%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis benzothiazole -2- methyl formates of the benzothiazole of embodiment 11 and carbon dioxide
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, benzothiazole（55.0 microlitres, 0.5 mM）, it is passed through carbon dioxide gas
Body, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, iodomethane is added（93 microlitres, 1.5 mMs）, 65 DEG C of stirrings
Reaction 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, column chromatography purification（With
Ethyl acetate/petroleum ether volume ratio is solvent for 1: 10 mixed solvent）, yield is 89%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis benzothiazole -2- methyl formates of the bisbenzothiazole of embodiment ten and carbon dioxide
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, benzothiazole（55.0 microlitres, 0.5 mM）, it is passed through carbon dioxide gas
Body, the lower 65 DEG C of stirring reactions of normal pressure 18 hours.Add iodomethane（93 microlitres, 1.5 mMs）, 65 DEG C of stirring reactions 1 hour.It is cold
But to room temperature, deionized water terminating reaction, product is extracted with ethyl acetate, column chromatography purification（With ethyl acetate/oil
Ether volume ratio is solvent for 1: 10 mixed solvent）, yield is 52%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis benzothiazole -2- hexyl formates of the benzothiazole of embodiment 13 and carbon dioxide
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, benzothiazole（55.0 microlitres, 0.5 mM）, it is passed through carbon dioxide gas
Body, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, 1- iodohexanes are added（222 microlitres, 1.5 mMs）, 65 DEG C are stirred
Mix reaction 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, column chromatography purification
（Mixed solvent with ethyl acetate/petroleum ether volume ratio as 1: 10 is as solvent）, yield is 80%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis 6- methoxyl group benzo thiophenes of the 6- methoxybenzothiazoles of embodiment 14 and carbon dioxide
Azoles -2- methyl formates
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, 6- methoxybenzothiazoles（82.5 milligrams, 0.5 mM）, it is passed through two
Carbon oxide gas, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, iodomethane is added（93 microlitres, 1.5 mMs）,
65 DEG C of stirring reactions 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, column chromatography
Purification（Mixed solvent with ethyl acetate/petroleum ether volume ratio as 1: 10 is as solvent）, yield is 82%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis 6- chloro benzothiazole -2- formic acid of the 6- chloro benzothiazoles of embodiment 15 and carbon dioxide
Methyl esters
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, 6- chloro benzothiazoles（84.99 milligrams, 0.5 mM）, it is passed through dioxy
Change carbon gas, the lower 80 DEG C of stirring reactions of normal pressure 18 hours.65 DEG C are cooled to, iodomethane is added（93 microlitres, 1.5 mMs）, 65
DEG C stirring reaction 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, and column chromatography is carried
It is pure（Mixed solvent with ethyl acetate/petroleum ether volume ratio as 1: 10 is as solvent）, yield is 75%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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 synthesis 1- tolimidazole -2- of the 1- tolimidazoles of embodiment 16 and carbon dioxide
Methyl formate
In reaction bulb, under argon gas protection catalyst is sequentially added（9.9 milligrams, 0.025 mM, 5 mol%）, potassium tert-butoxide
（0.0672 gram, 0.6 mM）, DMF（3.0 milliliter）, 1- tolimidazoles（60.0 microlitre, 0.5 mM）, it is passed through dioxy
Change carbon gas, the lower 80 DEG C of stirring reactions of normal pressure 24 hours.65 DEG C are cooled to, iodomethane is added（93 microlitres, 1.5 mMs）, 65
DEG C stirring reaction 1 hour.Room temperature is cooled to, deionized water terminating reaction, product is extracted with ethyl acetate, and column chromatography is carried
It is pure（Mixed solvent with ethyl acetate/petroleum ether volume ratio as 1: 10 is as solvent）, yield is 50%.
Product is dissolved in into CDCl3In（About 0.4 milliliter）, tube sealing, the survey on Unity Inova-400 type NMR instrument under room temperature
It is fixed to characterize.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. it is a kind of synthesis aromatic heterocycle formic ether compounds method, it is characterised in that comprise the following steps, in inert gas
In atmosphere, with the imidazoles villaumite containing single imines functionalization as catalyst, with heteroaromatic compound and carbon dioxide as raw material,
In the presence of alkali, synthesis under normal pressure is carried out；Reaction adds halogenated hydrocarbons, esterification to obtain aromatic heterocycle formate ester chemical combination after terminating
Thing；The chemical structural formula of the imidazoles villaumite containing single imines functionalization is as follows：
。
2. the method for synthesizing aromatic heterocycle formic ether compounds according to claim 1, it is characterised in that：The fragrance is miscellaneous
Cycle compound Bao Kuo oxazole compounds, thiazole compound, glyoxaline compound.
3. the method for synthesizing aromatic heterocycle formic ether compounds according to claim 1, it is characterised in that：The atmospheric reverse
Temperature is answered for 50～85 DEG C, the time is 12～24 hours；Esterification reaction temperature is 45～75 DEG C, and the time is 0.5～2 hour.
4. the method for synthesizing aromatic heterocycle formic ether compounds according to claim 1, it is characterised in that：The halogenated hydrocarbons
For idohydrocarbon；The alkali is potassium tert-butoxide or cesium carbonate；The reaction is carried out in organic solvent.
5. according to claim 4 synthesize aromatic heterocycle formic ether compounds method, it is characterised in that specifically include with
Lower step：In inert gas atmosphere, catalyst, alkali, solvent, heteroaromatic compound are added in reaction bulb successively；So
After be passed through carbon dioxide；At 50～85 DEG C, stirring reaction 12～24 hours under normal pressure；Halogenated hydrocarbons is subsequently adding, is esterified
Reaction obtains aromatic heterocycle formic ether compounds.
6. the method for synthesizing aromatic heterocycle formic ether compounds according to claim 1, it is characterised in that：The esterification is anti-
After should terminating, deionized water terminating reaction after reactant liquor cooling, then be extracted with ethyl acetate, process finally by column chromatography
To aromatic heterocycle formic ether compounds.
7. the method for synthesizing aromatic heterocycle formic ether compounds according to claim 1, it is characterised in that：In molar ratio,
The amount ranges of catalyst are the 1%～5% of heteroaromatic compound, the amount ranges of alkali be heteroaromatic compound 1.0～
1.5 again.
8. the method for synthesizing aromatic heterocycle formic ether compounds according to claim 7, it is characterised in that：The fragrance is miscellaneous
Cycle compound is Benzooxazole kind compound；With the gauge of material, the consumption of alkali is 1.2 times of Benzooxazole kind compound, is urged
The consumption of agent is 5 % of Benzooxazole kind compound, and the consumption of halogenated hydrocarbons is 3.0 times of Benzooxazole kind compound；Normal pressure
Reaction temperature is 80 DEG C, and the time is 18 hours；Esterification reaction temperature is 65 DEG C, and the time is 1 hour.
9. the imidazoles villaumite containing single imines functionalization is as catalyst in catalysis heteroaromatic compound with carbon dioxide reaction
Application.
10. the answering in aromatic heterocycle formic ether compounds are prepared as catalyst of the imidazoles villaumite containing single imines functionalization
With.
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| JP2014070026A (en) * | 2012-09-27 | 2014-04-21 | Univ Of Tokyo | Method for producing indole-3-carboxylic acids |
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| WO2014081618A1 (en) * | 2012-11-20 | 2014-05-30 | Merck Sharp & Dohme Corp. | Thrombin inhibitors |
| CN105001031A (en) * | 2015-07-27 | 2015-10-28 | 苏州大学 | Ionic type iron (III) complex with monophenol functionalization tetrahydroglyoxaline cations and preparation method and application thereof |
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