CN103333171B - The synthetic method of pyrroles [1,2-a] quinoxaline derivatives - Google Patents

The synthetic method of pyrroles [1,2-a] quinoxaline derivatives Download PDF

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CN103333171B
CN103333171B CN201310238303.2A CN201310238303A CN103333171B CN 103333171 B CN103333171 B CN 103333171B CN 201310238303 A CN201310238303 A CN 201310238303A CN 103333171 B CN103333171 B CN 103333171B
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tetralyl
formaldehyde
pyrroles
phenyl
quinoxaline
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CN103333171A (en
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韩世清
蒋增强
张�杰
童耀
何国珍
周双利
赵丹
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Nanjing Tech University
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Abstract

The present invention relates to the synthetic method of a kind of pyrroles [1,2-a] quinoxaline derivatives, belong to chemical preparation techniques field.With 2-halogen arylamine and 2-formyl radical azole compounds for raw material; be 1 ~ 3:1 by amount of substance ratio; get 2-formyl radical azole compounds and 2-halogen arylamine is dissolved in organic solvent; add alkaline medium; under protection of inert gas, 80 ~ 100 DEG C are stirred 12 ~ 24 hours reaction acquisition pyrroles [1; 2-a] quinoxaline derivatives, obtain pure products through cooling, extraction, drying, underpressure distillation.The method beneficial effect that application the present invention synthesizes pyrroles [1,2-a] quinoxaline derivatives is as follows: (1) reaction conditions is gentleer, and catalytic activity is high, reaction yield is up to more than 90%, the highlyest can reach 100%, and selectivity of product is high, it is wide that substrate expands scope.(2) catalyst system avoids the use of transition metal especially precious metal chemical complex, and cost is low, safe ready, and reaction system environmental pollution is little.

Description

The synthetic method of pyrroles [1,2-a] quinoxaline derivatives
Technical field
The present invention relates to organic synthesis field, be specifically related to the synthetic method of a kind of pyrroles [1,2-a] quinoxaline derivatives.
Background technology
Pyrroles [1,2-a] quinoxaline derivatives is a kind of important benzopyrazines heterocyclic compounds, there is higher thermostability and electron affinity energy, quinoxaline compounds is many important skeletons having important biomolecule active compound due to its inner distinctive molecular conjugation structure, is also widely used in fluorescence probe material simultaneously.The method of traditional synthesis pyrroles [1,2-a] quinoxaline is through two steps: first under the condition heated, generate 1-2-aminophenyl pyrroles by aryl 1,2-diamine compounds and 2,5-diethoxy tetrahydrofuran (THF), then add formic acid,
Reflux 10 ~ 13h obtains product, and productive rate is 28%(Cheeseman et al.Chem.Ind, and 1965,1382.).
In recent years, the method for many bibliographical informations synthesis pyrroles [1,2-a] quinoxaline is had: the people such as such as Kobayashi report and use BF 3(OEt 2) catalysis 1-2-Cyanophenylpyrrole and alkane ketone are under the existence of methylene dichloride, 0 DEG C is obtained by reacting pyrroles [1,2-a] quinoxaline derivatives (Kobayashi et al.Chem.Lett, 1998,551-552.); Harrak reported 1-2-nitrophenyl pyrroles at phosphorus oxychloride and N in 2007, react under the existence of dinethylformamide and first generate 1-2-nitrophenyl-1H-pyrrole-2-aldehyde, then pyrroles [1 is obtained through intramolecular C-N linked reaction, 2-a] quinoxaline (Harrak et al.Arkivoc, 2007,4,251-259.); Jonathan at 2009 annual reports by pyrrole-2-aldehyde and 2-Iodoaniline at CuI, K 3pO 4, NMP and sparteine catalysis under, 130 DEG C are stirred 24h and obtain pyrroles [1,2-a] quinoxaline derivatives (Jonathan T.Reeves, J.Org.Chem.2010,75,992 – 994.); Use AlCl 3/ BtH/THF mixed solvent catalysis 1-2-aminophenyl pyrrole derivative and corresponding aldehyde stir 1 ~ 2h at normal temperatures and obtain pyrroles [1,2-a] quinoxaline derivatives (Akhilesh et al.Eur.J.Org.Chem, 2011,4,6998-7010.); Maria in 2012 reports 1-2-nitrophenyl pyrroles and corresponding alcohol under the existence of fe and hydrochloric acid, and in air, backflow obtains pyrroles [1,2-a] quinoxaline derivatives (Maria et al.Org.Lett, 2012,4,251-259.).
But, above-mentioned various method all also exists some defects, reactions steps is more loaded down with trivial details, condition is harsher, productive rate is lower, aftertreatment is more difficult, need complicated part, use some virose solvents, especially use some transition-metal catalysts, fancy price, stronger toxicity and the dependence to high toxicity phosphorus-containing ligand seriously constrain its industrial applications in a lot of field.
Summary of the invention
The object of the invention is the synthetic method that a kind of pyrroles [1,2-a] quinoxaline derivatives is provided to improve the deficiencies in the prior art.The method low cost, without transition metal-catalyzed, productive rate is high, substrate applicability is wide.
The technical solution used in the present invention is: the synthetic method of a kind of pyrroles [1,2-a] quinoxaline derivatives, with 2-halogen arylamine and 2-formyl radical azole compounds for reactant synthesizes pyrroles [1,2-a] quinoxaline derivatives: specifically comprise the following steps:
Be 1 ~ 3:1 by 2-halogen arylamine and 2-formyl radical azole compounds amount of substance ratio, get 2-halogen arylamine and 2-formyl radical azole compounds is dissolved in organic solvent, add alkaline medium, under protection of inert gas, 80 ~ 100 DEG C are stirred reaction in 12 ~ 24 hours and obtain pyrroles [1,2-a] quinoxaline derivatives;
Reaction process is as follows:
The structural formula of preferred described 2-halogen arylamine is as follows:
wherein X 1can be selected from respectively: the one in chlorine, bromine or iodine; Y, Y 1and Y 2can be selected from respectively: the one in carbon or nitrogen; R 1can be selected from respectively: the one in hydrogen, methyl, methoxyl group, fluorine-based, chloro, nitro, benzoyl, cyano group or 3-methyl fluoride.
2-halogen arylamine is selected from: 2-Iodoaniline 2-bromaniline 2-chloroaniline 2-amino-3-iodine pyridine 2-amino-3-bromopyridine 2-amino-3-chloropyridine 5-amino-4-iodine pyrimidine 5-amino-4-bromo pyrimi piperidine 5-amino-4-chlorine pyrimidine 4-amino-3-iodine benzotrifluoride 4-amino-3-ioxynil 4-amino-3-iodo-benzoic acid methyl esters The fluoro-2-Iodoaniline of 5- 4-amino-3-5 bromine benzotrifluoride 4-amino-3-Brominal 4-amino-3-methyl-bromobenzoate The fluoro-2-bromaniline of 5- 4-amino-3-chlorobenzotrifluoride 4-amino-3-6-chlorophenyl nitrile 4-amino-3-chloro benzoic ether The fluoro-2-chloroaniline of 5- The iodo-5-5-flumethiazine of 2-amino-3- The iodo-nicotinic acid nitrile of 6-amino-5- 6-amino-5-iodine methyl nicotinate The fluoro-3-iodine pyridine-2-amine of 6- The bromo-2-chlorin-5-trifluoro picoline of 3- The bromo-nicotinic acid nitrile of 6-amino-5- 6-amino-5-bromo-nicotinic acid methyl esters The bromo-6-fluorine pyridine-2-amine of 3- 2-amido-3-5-trifluoro picoline The chloro-nicotinic acid nitrile of 6-amino-5- 6-amino-5-chlorine apellagrin methyl esters The chloro-6-fluorine pyridine-2-amine of 3- The iodo-2-trifluoromethyl pyrimidine-5-amine of 4- The bromo-2-trifluoromethyl pyrimidine-5-amine of 4- The chloro-2-trifluoromethyl pyrimidine-5-amine of 4- 5-amido-4-iodine pyrimidine-2-nitrile 5-amido-4-bromo pyrimi piperidine-2-nitrile 5-amido-4-chlorine pyrimidine-2-nitrile Methyl 5-amido-4 chlorine pyrimidine-2-carboxyl Methyl 5-amido-4 bromo pyrimi piperidine-2-carboxyl Methyl 5-amido-4 iodine pyrimidine-2-carboxyl The fluoro-4-iodine pyrimidine-5-amido of 2- The fluoro-4-bromo pyrimi piperidine-5-amido of 2- Or the fluoro-4-chlorine pyrimidine-5-amido of 2- In one.
The structural formula of preferred described 2-formyl radical azole compounds is as follows:
wherein Z can be selected from respectively: the one in carbon or nitrogen, Het can be selected from respectively: phenyl, 2-aminomethyl phenyl, 2-p-methoxy-phenyl, 2-fluorophenyl, 2-chloro-phenyl-, 2-bromophenyl, 2-iodophenyl, 2-benzoylphenyl, 2-nitrophenyl, 3-aminomethyl phenyl, 3-p-methoxy-phenyl, 3-fluorophenyl, 3-chloro-phenyl-, 3-bromophenyl, 3-iodophenyl, 3-benzoylphenyl, 3-nitrophenyl, 4-aminomethyl phenyl, 4-p-methoxy-phenyl, 4-fluorophenyl, 4-chloro-phenyl-, 4-bromophenyl, 4-iodophenyl, 4-benzoylphenyl, 4-nitrophenyl, 5-aminomethyl phenyl, 5-p-methoxy-phenyl, 5-fluorophenyl, 5-chloro-phenyl-, 5-bromophenyl, 5-iodophenyl, 5-benzoylphenyl, 5-nitrophenyl, 1,2,3,4-tetralyl, 5-methyl isophthalic acid, 2,3,4-tetralyl, 5-methoxyl group-1,2,3,4-tetralyl, fluoro-1,2,3, the 4-tetralyl of 5-, chloro-1,2,3, the 4-tetralyl of 5-, bromo-1,2,3, the 4-tetralyl of 5-, iodo-1,2,3, the 4-tetralyl of 5-, 5-benzoyl-1,2,3,4-tetralyl, 5-nitro-1,2,3,4-tetralyl, 6-methyl isophthalic acid, 2,3,4-tetralyl, 6-methoxyl group-1,2,3,4-tetralyl, fluoro-1,2,3, the 4-tetralyl of 6-, chloro-1,2,3, the 4-tetralyl of 6-, bromo-1,2,3, the 4-tetralyl of 6-, iodo-1,2,3, the 4-tetralyl of 6-, 6-benzoyl-1,2,3,4-tetralyl, 6-nitro-1,2,3,4-tetralyl, 7-methyl isophthalic acid, 2,3,4-tetralyl, 7-methoxyl group-1,2,3,4-tetralyl, fluoro-1,2,3, the 4-tetralyl of 7-, chloro-1,2,3, the 4-tetralyl of 7-, bromo-1,2,3, the 4-tetralyl of 7-, iodo-1,2,3, the 4-tetralyl of 7-, 7-benzoyl-1,2,3,4-tetralyl, one in 7-nitro-1,2,3,4-tetralyl or 4,5,6,7,8,9-hexahydro--1H-cyclooctane base.
2-formoxyl azole compounds is selected from: pyrrole-2-aldehyde Imidazoles-2-formaldehyde Pyrazoles-2-formaldehyde 3,5-dimethyl-2-pyrrole aldehyde 3-methyl pyrazole-5-formaldehyde 4-methyl-imidazoles-2-formaldehyde 5-phenyl-pyrrol-2-formaldehyde 4-phenyl-pyrrol-2-formaldehyde 3-phenyl-pyrrol-2-formaldehyde Indoles-2 formaldehyde 4-Methvl-indole-2 formaldehyde 5-Methvl-indole-2 formaldehyde 6-Methvl-indole-2 formaldehyde 7-Methvl-indole-2 formaldehyde 4-Methoxv-indole-2 formaldehyde 5-Methoxv-indole-2 formaldehyde 6-Methoxv-indole-2 formaldehyde 7-Methoxv-indole-2 formaldehyde 4-is fluorine-based-indoles-2 formaldehyde 5-is fluorine-based-indoles-2 formaldehyde 6-is fluorine-based-indoles-2 formaldehyde 7-is fluorine-based-indoles-2 formaldehyde 4-chloro-indoles-2 formaldehyde 5-chloro-indoles-2 formaldehyde 6-chloro-indoles-2 formaldehyde 7-chloro-indoles-2 formaldehyde 4-bromo-indoles-2 formaldehyde 5-bromo-indoles-2 formaldehyde 6-bromo-indoles-2 formaldehyde 7-bromo-indoles-2 formaldehyde 4-iodo-indoles-2 formaldehyde 5-iodo-indoles-2 formaldehyde 6-iodo-indoles-2 formaldehyde 7-iodo-indoles-2 formaldehyde 4-nitro-indole-2 formaldehyde 5-nitro-indole-2 formaldehyde 6-nitro-indole-2 formaldehyde 7-nitro-indole-2 formaldehyde Benzimidazolyl-2 radicals formaldehyde 4-nitro-benzimidazolyl-2 radicals formaldehyde 5-nitro-benzimidazolyl-2 radicals formaldehyde 6-nitro-benzimidazolyl-2 radicals formaldehyde 4-iodo-benzimidazolyl-2 radicals formaldehyde 5-iodo-benzimidazolyl-2 radicals formaldehyde 6-iodo-benzimidazolyl-2 radicals formaldehyde 7-iodo-benzimidazolyl-2 radicals formaldehyde 4-bromo-benzimidazolyl-2 radicals formaldehyde 5-bromo-benzimidazolyl-2 radicals formaldehyde 6-bromo-benzimidazolyl-2 radicals formaldehyde 7-bromo-benzimidazolyl-2 radicals formaldehyde 4-chloro-benzimidazolyl-2 radicals formaldehyde 5-chloro-benzimidazolyl-2 radicals formaldehyde 6-chloro-benzimidazolyl-2 radicals formaldehyde 7-chloro-benzimidazolyl-2 radicals formaldehyde 4-is fluorine-based-benzimidazolyl-2 radicals formaldehyde 5-is fluorine-based-benzimidazolyl-2 radicals formaldehyde 6-is fluorine-based-benzimidazolyl-2 radicals formaldehyde 7-is fluorine-based-benzimidazolyl-2 radicals formaldehyde 4-methyl-benzoimidazole-2 formaldehyde 5-methyl-benzoimidazole-2 formaldehyde 6-methyl-benzoimidazole-2 formaldehyde 7-methyl-benzoimidazole-2 formaldehyde 4-Methoxy-benzoimidazol-2 formaldehyde 5-Methoxy-benzoimidazol-2 formaldehyde 6-Methoxy-benzoimidazol-2 formaldehyde 7-Methoxy-benzoimidazol-2 formaldehyde 4,5-dihydro-benzindole-2-formaldehyde 6-methyl-4,5-dihydro-benzindole-2-formaldehyde 7-methyl-4,5-dihydro-benzindole-2-formaldehyde 8-methyl-4,5-dihydro-benzindole-2-formaldehyde 9-methyl-4,5-dihydro-benzindole-2-formaldehyde 6-methoxyl group-4,5-dihydro-benzindole-2-formaldehyde 7-methoxyl group-4,5-dihydro-benzindole-2-formaldehyde 8-methoxyl group-4,5-dihydro-benzindole-2-formaldehyde 9-methoxyl group-4,5-dihydro-benzindole-2-formaldehyde Or 4,5,6,7,8,9-hexahydro-1H-cyclooctane-pyrrole-2-aldehyde In one.
Described alkaline medium is t-butoxide salt or hydroxide radical metal-salt, and molecular formula is (CH 3) 3cOM and M (OH), wherein metal M is selected from lithium (Li), sodium (Na), potassium (K); Be more preferably the one in trimethyl carbinol lithium, sodium tert-butoxide, potassium tert.-butoxide, lithium hydroxide or sodium hydroxide; Preferred alkaline medium and 2-formyl radical azole compounds amount of substance ratio are 1 ~ 3:1.
Preferred described organic solvent is the one in dimethyl sulfoxide (DMSO), dimethyl formamide (DMF) or toluene.The amount of organic solvent is solubilizing reaction raw material.
Preferably described inert nitrogen gas or argon gas.
In technique scheme, react and need inert nitrogen gas or argon shield, 80 ~ 100 DEG C are stirred end in 12 ~ 24 hours, and system obtains product through cooling, extraction, drying, underpressure distillation, can obtain highly purified product after recrystallization.
Due to the utilization of technique scheme, the present invention compared with prior art has following advantages:
1. due to alkaline medium, and the application of reactant 2-formyl radical azole compounds and 2-halogen arylamine, this reaction can be carried out at relatively low temperatures, and reaction conditions is simple, gentle, and reaction yield is high, can reach the productive rate of 100%.
2. with t-butoxide salt or hydroxide radical metal-salt for alkaline medium, reaction system only need add organic solvent just can obtain target product, solves the problem that the increase of final product Financial cost and transition metal may remain, reduces the pollution to environment; Product can complete aftertreatment through overcooling, extraction, drying, underpressure distillation, washing, recrystallization, and aftertreatment is simple, convenient.
3. above-mentioned set up catalyst system, suitability is extensive, the transformation efficiency of substrate and the productive rate of product all very high, expanded the industrial applications in a lot of field.
Embodiment
Below in conjunction with embodiment, the invention will be further described, but embodiment does not limit the present invention in any way:
Embodiment 1:
The present embodiment is the synthesis of pyrroles [1,2-a] quinoxaline, and with 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in 25ml eggplant-shape bottle, 0.215mmol2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 99%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 DEG C; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s; 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m; 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 11h 9n 2(M *) 169.0760, found:169.0769.
Embodiment 2:
The present embodiment is the synthesis of pyrroles [1,2-a] quinoxaline, and with 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, argon shield, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 99%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 DEG C; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s; 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m; 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 11h 9n 2(M *) 169.0760, found:169.0769.
Embodiment 3:
The present embodiment is the synthesis of pyrroles [1,2-a] quinoxaline, and with 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in 25ml eggplant-shape bottle, 0.43mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 99%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 DEG C; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s; 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m; 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 11h 9n 2(M *) 169.0760, found:169.0769.
Embodiment 4:
The present embodiment is the synthesis of pyrroles [1,2-a] quinoxaline, and with 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in 25ml eggplant-shape bottle, 0.645mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 99%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 DEG C; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s; 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m; 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 11h 9n 2(M *) 169.0760, found:169.0769.
Embodiment 5:
The present embodiment is the synthesis of pyrroles [1,2-a] quinoxaline, and with 2-Iodoaniline, pyrroles-2 formaldehyde, potassium hydroxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol sodium hydroxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 87%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 DEG C; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s; 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m; 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 11h 9n 2(M *) 169.0760, found:169.0769.
Embodiment 6:
The present embodiment is the synthesis of pyrroles [1,2-a] quinoxaline, and with 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol trimethyl carbinol lithium; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 83%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 DEG C; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s; 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m; 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 11h 9n 2(M *) 169.0760, found:169.0769.
Embodiment 7:
The present embodiment is the synthesis of pyrroles [1,2-a] quinoxaline, and with 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl formamide (DMF) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl formamide (DMF) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 76%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 DEG C; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s; 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m; 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 11h 9n 2(M *) 169.0760, found:169.0769.
Embodiment 8:
The present embodiment is the synthesis of pyrroles [1,2-a] quinoxaline, and with 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, toluene for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide, then add 1.5ml toluene, nitrogen protection, 100 DEG C are stirred 24 hours, and solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 56%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 DEG C; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s; 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m; 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 11h 9n 2(M *) 169.0760, found:169.0769.
Embodiment 9:
The present embodiment is the synthesis of pyrroles [1,2-a] quinoxaline, and with 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.215mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 50%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 DEG C; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s; 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m; 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 11h 9n 2(M *) 169.0760, found:169.0769.
Embodiment 10:
The present embodiment is the synthesis of pyrroles [1,2-a] quinoxaline, and with 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.645mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 99%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 DEG C; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s; 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m; 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 11h 9n 2(M *) 169.0760, found:169.0769.
Embodiment 11:
The present embodiment is the synthesis of pyrroles [1,2-a] quinoxaline, and with 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 80 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 65%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 DEG C; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s; 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m; 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 11h 9n 2(M *) 169.0760, found:169.0769.
Embodiment 12:
The present embodiment is the synthesis of pyrroles [1,2-a] quinoxaline, and with 2-Iodoaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 12 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 51%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 DEG C; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s; 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m; 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 11h 9n 2(M *) 169.0760, found:169.0769.
Embodiment 13:
The present embodiment be the synthesis of imidazoles [1,2-a] quinoxaline with 2-bromaniline, imidazoles-2-formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol imidazoles-2-formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-bromaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 91%, this imidazoles [1,2-a] quinoxaline fusing point is 124-126 DEG C; Nucleus magnetic hydrogen spectrum (400Hz, CDCl 3); δ 9.13 (s, 1H), 8.15-8.13 (m, 2H), 7.93-7.91 (m, 1H), 7.83 (s, 1H), 7.70-7.66 (m, 1H), 7.63-7.59 (m, 1H); High resolution mass spectrum: m/z (%), calcd for C 10h 8n 3(M *) 170.0712, found:170.0724.
Embodiment 14:
The present embodiment is the synthesis of pyrroles [1,2-a] quinoxaline, and with 2-chloroaniline, pyrroles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrroles-2 formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-chloroaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 53%, this pyrroles [1,2-a] quinoxaline fusing point is 131-133 DEG C; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3): δ 8.79 (s, 1H), 7.94 (d, J=7.95Hz, 1H), 7.89 (s; 1H), 7.82 (d, J=8.15Hz, 1H), 7.51-7.48 (m; 1H), 7.44-7.41 (m, 1H), 6.88-6.86 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 11h 9n 2(M *) 169.0760, found:169.0769.
Embodiment 15:
The present embodiment is the synthesis of 1,3-Dimethyl-pyrrol [1,2-a] quinoxaline, and with 2-Iodoaniline, 3,5-dimethyl-2-pyrrole aldehydes, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol 3,5-dimethyl-2-pyrrole aldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline; 0.54mmol potassium tert.-butoxide, then add 1.5ml dimethyl sulfoxide (DMSO), nitrogen protection; 100 DEG C are stirred 24 hours, and solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 92%, this 1,3-Dimethyl-pyrrol [1,2-a] quinoxaline fusing point is 65-69 DEG C; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3); δ 8.64 (s, 1H), 8.13 (d, J=7.4Hz, 1H), 7.88 (d; J=7.0Hz, 1H), 7.41-7.33 (m, 2H), 6.39 (s; 1H), 2.86 (s, 3H), 2.41 (s, 3H); High resolution mass spectrum: m/z (%), calcd for C 13h 13n 2(M *) 197.1073, found:197.1086.
Embodiment 16:
The present embodiment is the synthesis of imidazoles [1,2-a] quinoxaline, and with 2-Iodoaniline, imidazoles-2-formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol imidazoles-2-formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 100%, this imidazoles [1,2-a] quinoxaline fusing point is 124-126 DEG C; Nucleus magnetic hydrogen spectrum (400Hz, CDCl 3); δ 9.13 (s, 1H), 8.15-8.13 (m, 2H), 7.93-7.91 (m, 1H), 7.83 (s, 1H), 7.70-7.66 (m, 1H), 7.63-7.59 (m, 1H); High resolution mass spectrum: m/z (%), calcd for C 10h 8n 3(M *) 170.0712, found:170.0724.
Embodiment 17:
The present embodiment is the synthesis of benzoglyoxaline [1,2-a] quinoxaline, and with 2-Iodoaniline, benzimidazolyl-2 radicals formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol benzimidazolyl-2 radicals formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 98%, this benzoglyoxaline [1,2-a] quinoxaline fusing point is 182-184 DEG C; Nucleus magnetic hydrogen spectrum (300Hz, CDCl 3): δ 9.20 (s, 1H), 8.35 (d; J=8.1Hz, 1H), 8.28 (d; J=7.4Hz, 1H), 8.12 (d; J=7.8Hz, 1H), 8.06 (d; J=7.3Hz, 1H), 7.72-7.69 (m; 1H), 7.58-7.52 (m, 3H); High resolution mass spectrum: m/z (%), calcd for C 14h 10n 3(M *) 219.0797, found:219.0789.
Embodiment 18:
The present embodiment is the synthesis of indoles [1,2-a] quinoxaline, and with 2-Iodoaniline, indoles-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol indoles-2 formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 94%, this indoles [1,2-a] quinoxaline fusing point is 109-112 DEG C; Nucleus magnetic hydrogen spectrum (300Hz, CDCl 3): δ 8.94 (s, 1H), 8.44 (m, 2H), 7.98 (m, 2H); 7.62 (t, J=7.7Hz, 1H), 7.56 (t, J=7.5Hz; 1H), 7.47-7.42 (m, 2H), 7.15 (s, 1H); High resolution mass spectrum: m/z (%), calcd for C 15h 11n 2(M *) 219.0916, found:219.0933.
Embodiment 19:
The present embodiment is the synthesis of 9-methoxy-Indole [1,2-a] quinoxaline, and with 2-Iodoaniline, 5-Methoxv-indole-2 formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol 5-Methoxv-indole-2 formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 93%, this 9-methoxy-Indole [1,2-a] quinoxaline fusing point is 133-135 DEG C; Nucleus magnetic hydrogen spectrum (300Hz, CDCl 3): δ 8.89 (s, 1H), 8.35 (d, J=8.3Hz, 1H); 8.27 (d, J=8.3Hz, 1H), 7.97 (d; J=7.8Hz, 1H), 7.58 (t, J=7.8Hz; 1H), 7.41 (t, J=7.7Hz, 1H); 7.28 (broads, 1H), 7.18-7.16 (m, 1H); 7.03 (s, 1H), 3.92 (s, 3H); High resolution mass spectrum: m/z (%), calcd for C 16h 13n 2o (M *) 249.1022, found:249.1028.
Embodiment 20:
The present embodiment is 8,9,10,11,12, the synthesis of 13-hexahydro--1H-cyclooctane-pyrroles [1,2-a] quinoxaline, with 2-Iodoaniline, 4,5,6,7,8,9-hexahydro--1H-cyclooctane-pyrrole-2-aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) are raw material, and its reaction formula is as follows:
Preparation method: add 0.215mmol 4 in 25ml eggplant-shape bottle, 5,6; 7; 8,9-hexahydro--1H-cyclooctane-pyrrole-2-aldehyde, 0.215mmol 2-Iodoaniline; 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, argon shield, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 91%, this 8,9,10,11,12,13-hexahydro--1H-cyclooctane-pyrroles [1,2-a] quinoxaline is soft type solid; Nucleus magnetic hydrogen spectrum (300Hz, CDCl 3) δ 8.64 (s, 1H), 8.17 (dd, J=8.4,1.2Hz; 1H), 7.94 (dd, J=7.8,1.8Hz, 1H); 7.47-7.36 (m, 2H), 6.70 (s, 1H); 3.40-3.37 (m, 2H), 2.82-2.79 (m, 2H); 1.99-1.92 (m, 2H), 1.73-1.67 (m, 2H); 1.58-1.52 (m, 2H), 1.38-1.32 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 17h 19n 2o (M *) 251.1542, found:251.1566.
Embodiment 21:
The present embodiment is the synthesis of 11-methoxyl group-8,9-dihydrobenzo indoles [1,2-a] quinoxaline, and with 2-Iodoaniline, 7-methoxyl group-4,5-dihydros-benzindole-2-formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol 7-methoxyl group-4 in 25ml eggplant-shape bottle; 5-dihydro-benzindole-2-formaldehyde; 0.215mmol 2-Iodoaniline; 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 91%, this 11-methoxyl group-8,9-dihydrobenzo indoles [1,2-a] quinoxaline fusing point is 174-178 DEG C; Nucleus magnetic hydrogen spectrum (300Hz, CDCl 3): δ 8.71 (s, 1H), 8.19 (d, J=8.3Hz; 1H), 7.94 (d, J=8.0Hz; 1H), 7.64 (d, J=8.6Hz; 1H), 7.42 (t, J=7.2Hz; 1H), 7.34 (t, J=7.8Hz; 1H), 6.93-6.92 (m, 1H); 6.83-6.80 (m, 1H), 6.78 (s; 1H), 3.87 (s, 3H); (2.97 t, J=6.5Hz, 2H); (2.81 t, J=7.3Hz, 2H); High resolution mass spectrum: m/z (%), calcd for C 20h 17n 2o (M *) 301.1335, found:301.1349.
Embodiment 22:
The present embodiment is the synthesis of 1-phenyl-pyrrol [1,2-a] quinoxaline, and with 2-Iodoaniline, 5 – phenyl-pyrrol-2-formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol 5 – phenyl-pyrrol-2-formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 94%, this 1-phenyl-pyrrol [1,2-a] quinoxaline is soft type solid; Nucleus magnetic hydrogen spectrum (500Hz, CDCl 3): δ 8.70 (s, 1H), 7.82 (d, J=8.0Hz; 1H), 7.40-7.35 (m, 5H), 7.29 (d; J=8.5Hz, 1H), 7.22 (t, J=7.7Hz; 1H), 7.00 (t, J=8.1Hz, 1H); 6.84 (d, J=4.0Hz, 1H); 6.64 (d, J=4.0Hz, 1H); High resolution mass spectrum: m/z (%), calcd for C 17h 13n 2(M *) 245.1073, found:245.1094.
Embodiment 23:
The present embodiment is the synthesis of 9-fluoro-7-skatole [1,2-a] quinoxaline, and with 2-Iodoaniline, the fluoro-3-skatole of 5--2-formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add the fluoro-3-skatole of 0.215mmol 5--2-formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 91%, this 9-fluoro-7-skatole [1,2-a] quinoxaline is 170-171 DEG C; Nucleus magnetic hydrogen spectrum (400Hz, CDCl 3): δ 8.88 (s, 1H), 8.25-8.21 (m, 2H); 7.93 (dd, J=7.9,1.4Hz, 1H); 7.56-7.52 (m, 1H), 7.45 (dd; J=8.9,2.6Hz, 1H); 7.40-7.36 (m, 1H), 7.27-7.22 (m; 1H), 2.57 (s, 3H); High resolution mass spectrum: m/z (%), calcd forC 16h 12fN 2o (M *) 251.0979, found:251.0958.
Embodiment 24:
The present embodiment is the synthesis of 2-methyl pyrazole [1,5-a] quinoxaline, and with 2-Iodoaniline, 3-methyl pyrazole-5-formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol 3-methyl pyrazole-5-formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-Iodoaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 93%, this 2-methyl pyrazole [1,5-a] quinoxaline fusing point is 89-91 DEG C; Nucleus magnetic hydrogen spectrum (400Hz, CDCl 3): δ 8.95 (s, 1H), 8.43 (dd; J=8.3,1.0Hz, 1H); 8.04 (dd, J=8.1,1.0Hz; 1H), 7.68-7.63 (m, 1H); 7.55-7.51 (m, 1H), 6.64 (s; 1H), 2.59 (s, 3H); High resolution mass spectrum: m/z (%), calcd for C 11h 10n 3o (M *) 184.0869, found:184.0886.
Embodiment 25:
The present embodiment is the synthesis of 2-methyl pyrazole [1,5-a] quinoxaline, and with 2-chloroaniline, 3-methyl pyrazole-5-formaldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol 3-methyl pyrazole-5-formaldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-chloroaniline, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 41%, this 2-methyl pyrazole [1,5-a] quinoxaline fusing point is 89-91 DEG C; Nucleus magnetic hydrogen spectrum (400Hz, CDCl 3): δ 8.95 (s, 1H), 8.43 (dd; J=8.3,1.0Hz, 1H); 8.04 (dd, J=8.1,1.0Hz; 1H), 7.68-7.63 (m, 1H); 7.55-7.51 (m, 1H), 6.64 (s; 1H), 2.59 (s, 3H); High resolution mass spectrum: m/z (%), calcd for C 11h 10n 3o (M *) 184.0869, found:184.0886.
Embodiment 26:
The present embodiment is the synthesis of pyrido pyrroles [1,2-a] pyrazine, and with 2-amino-3-iodine pyridine, pyrrole-2-aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrrole-2-aldehyde in 25ml eggplant-shape bottle, 0.215mmol 2-amino-3-iodine pyridine, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, argon shield, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 94%, this pyrido pyrroles [1,2-a] pyrazine fusing point is 170-172 DEG C; Nucleus magnetic hydrogen spectrum (300Hz, CDCl 3): δ 9.01 (s, 1H), 8.76-8.74 (m, 1H), 8.22-8.19 (m, 1H), 7.97-7.96 (m, 1H), 7.45 (dd, J=8.2,4.6Hz, 1H), 6.96-6.92 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 10h 8n 3(M *) 170.0712, found:170.0729.
Embodiment 27:
The present embodiment is the synthesis of pyrido pyrroles [1,2-h] pteridine, and with 5-amino-4-iodine pyrimidine, pyrrole-2-aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrrole-2-aldehyde in 25ml eggplant-shape bottle, 0.215mmol 5-amino-4-iodine pyrimidine, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 90%, this pyrido pyrroles [1,2-h] pteridine fusing point is 122-123 DEG C; Nucleus magnetic hydrogen spectrum (300Hz, CDCl 3): δ 9.24 (s, 1H), 9.06 (s, 1H), 8.82 (s, 1H), 8.34-8.33 (m, 1H), 7.05-7.04 (m, 1H), 6.99-6.97 (m, 1H); High resolution mass spectrum: m/z (%), calcd for C 9h 7n 4(M *) 171.0665, found:171.0676.
Embodiment 28:
The present embodiment is the synthesis of 8-trifluoromethyl pyrpole [1,2-a] quinoxaline, and with 4-amino-3-iodine phenylfluoroform, pyrrole-2-aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrrole-2-aldehyde in 25ml eggplant-shape bottle, 0.215mmol 4-amino-3-iodine phenylfluoroform, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.Productive rate 93%, this 8-trifluoromethyl pyrpole [1,2-a] quinoxaline fusing point is 133-134 DEG C; Nucleus magnetic hydrogen spectrum (300Hz, CDCl 3): δ 8.85 (s, 1H), 8.09 (s, 1H), 8.05-8.03 (m; 1H), 7.98-7.96 (m, 1H), 7.67-7.65 (m, 1H); 6.97-6.96 (m, 1H), 6.94-6.92 (m, 1H); High resolution mass spectrum: m/z (%), calcd for C 12h 8f 3n 2(M *) 237.0634, found:237.0650.
Embodiment 29:
The present embodiment is the synthesis of 8-formonitrile HCN pyrroles [1,2-a] quinoxaline, and with 4-amino-3-ioxynil, pyrrole-2-aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrrole-2-aldehyde in 25ml eggplant-shape bottle, 0.215mmol 4-amino-3-ioxynil, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 90%, this 8-formonitrile HCN pyrroles [1,2-a] quinoxaline fusing point is 273-275 DEG C; Nucleus magnetic hydrogen spectrum (400Hz, d-6DMSO): δ 9.15 (s, 1H), 9.01 (d; J=1.5Hz, 1H), 8.76-8.74 (m; 1H), 8.05 (d, J=8.4Hz; 1H), 7.94 (dd, J=8.4; 1.6Hz, 1H), 7.31-7.29 (m; 1H), 7.13 (m, 1H); High resolution mass spectrum: m/z (%), calcd for C 12h 8n 3(M *) 194.0712, found:194.0728.
Embodiment 30:
The present embodiment is the synthesis of 8-methyl-formiate pyrroles [1,2-a] quinoxaline, and with 4-amino-3-iodo-benzoic acid methyl esters, pyrrole-2-aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrrole-2-aldehyde in 25ml eggplant-shape bottle, 0.215mmol 4-amino-3-iodo-benzoic acid methyl esters, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 90%, this 8-methyl-formiate pyrroles [1,2-a] quinoxaline fusing point is 235-240 DEG C; Nucleus magnetic hydrogen spectrum (400Hz, d-6DMSO): δ 8.95 (s, 1H); 8.78-8.77 (m, 1H), 8.64-8.63 (m; 1H), 8.00 (dd, J=8.4; 1.5Hz, 1H), 7.93 (d; J=8.4Hz, 1H), 7.06 (m; 1H), 6.97-6.95 (m, 1H); High resolution mass spectrum: m/z (%), calcd for C 12h 9n 2o 2(M *) 213.0658, found:213.0670.
Embodiment 31:
The present embodiment is the synthesis of 7-fluorine pyrroles [1,2-a] quinoxaline, and with the fluoro-2-Iodoaniline of 5-, pyrrole-2-aldehyde, potassium tert.-butoxide, dimethyl sulfoxide (DMSO) for raw material, its reaction formula is as follows:
Preparation method: add 0.215mmol pyrrole-2-aldehyde in 25ml eggplant-shape bottle, the fluoro-2-Iodoaniline of 0.215mmol 5-, 0.54mmol potassium tert.-butoxide; add 1.5ml dimethyl sulfoxide (DMSO) again, nitrogen protection, 100 DEG C are stirred 24 hours; solution colour becomes transparent color, has product to generate.
Reaction solution is filtered after cooling, extraction, drying, underpressure distillation, washing, recrystallization and obtains white solid.
Productive rate 96%, this 7-fluorine pyrroles [1,2-a] quinoxaline fusing point is 166-167 DEG C; Nucleus magnetic hydrogen spectrum (400Hz, CDCl 3): δ 8.78 (s, 1H), 7.86 (broad s, 1H), 7.78 (dd, J=9.0; 5.0Hz, 1H), 7.61 (dd, J=9.4,2.7Hz; 1H), 7.26-7.21 (m, 1H), 6.90-6.85 (m, 2H); High resolution mass spectrum: m/z (%), calcd for C 11h 8fN 2(M *) 187.0666, found:187.0680.

Claims (3)

1. the preparation method of the pyrrole quinoxaline derivatives of a formula Ι, it is characterized in that: getting halogen aromatic amines and formyl radical azole compounds or formylpyrrole compounds is raw material, be that 1 ~ 3:1 is dissolved in organic solvent by amount of substance ratio, add alkaline medium, under protection of inert gas, 80 ~ 100 DEG C are stirred reaction in 12 ~ 24 hours, obtain Ι compound;
The structural formula of wherein said halogen aromatic amines is as follows: wherein X 1for the one in chlorine, bromine or iodine; Y, Y 1with the one that Y is in carbon or nitrogen separately; R 1for the one in hydrogen, methyl, methoxyl group, fluorine-based, chloro, nitro, benzoyl, cyano group or trifluoromethyl; The structural formula of described formyl radical azole compounds or formylpyrrole compounds is as follows:
wherein Z is the one in carbon or nitrogen, Het is phenyl, 2-aminomethyl phenyl, 2-p-methoxy-phenyl, 2-fluorophenyl, 2-chloro-phenyl-, 2-bromophenyl, 2-iodophenyl, 2-benzoylphenyl, 2-nitrophenyl, 3-aminomethyl phenyl, 3-p-methoxy-phenyl, 3-fluorophenyl, 3-chloro-phenyl-, 3-bromophenyl, 3-iodophenyl, 3-benzoylphenyl, 3-nitrophenyl, 4-aminomethyl phenyl, 4-p-methoxy-phenyl, 4-fluorophenyl, 4-chloro-phenyl-, 4-bromophenyl, 4-iodophenyl, 4-benzoylphenyl, 4-nitrophenyl, 5-aminomethyl phenyl, 5-p-methoxy-phenyl, 5-fluorophenyl, 5-chloro-phenyl-, 5-bromophenyl, 5-iodophenyl, 5-benzoylphenyl, 5-nitrophenyl, 1,2,3,4-tetralyl, 5-methyl isophthalic acid, 2,3,4-tetralyl, 5-methoxyl group-1,2,3,4-tetralyl, fluoro-1,2,3, the 4-tetralyl of 5-, chloro-1,2,3, the 4-tetralyl of 5-, bromo-1,2,3, the 4-tetralyl of 5-, iodo-1,2,3, the 4-tetralyl of 5-, 5-benzoyl-1,2,3,4-tetralyl, 5-nitro-1,2,3,4-tetralyl, 6-methyl isophthalic acid, 2,3,4-tetralyl, 6-methoxyl group-1,2,3,4-tetralyl, fluoro-1,2,3, the 4-tetralyl of 6-, chloro-1,2,3, the 4-tetralyl of 6-, bromo-1,2,3, the 4-tetralyl of 6-, iodo-1,2,3, the 4-tetralyl of 6-, 6-benzoyl-1,2,3,4-tetralyl, 6-nitro-1,2,3,4-tetralyl, 7-methyl isophthalic acid, 2,3,4-tetralyl, 7-methoxyl group-1,2,3,4-tetralyl, fluoro-1,2,3, the 4-tetralyl of 7-, chloro-1,2,3, the 4-tetralyl of 7-, bromo-1,2,3, the 4-tetralyl of 7-, iodo-1,2,3, the 4-tetralyl of 7-, 7-benzoyl-1,2,3,4-tetralyl, one in 7-nitro-1,2,3,4-tetralyl or 4,5,6,7,8,9-hexahydro--1H-cyclooctane base, described alkaline medium is the one in trimethyl carbinol lithium, sodium tert-butoxide, potassium tert.-butoxide, lithium hydroxide or sodium hydroxide, alkaline medium and formyl radical azole compounds or formylpyrrole compounds amount of substance ratio are 1 ~ 3:1.
2. synthetic method according to claim 1, is characterized in that: described organic solvent is the one in dimethyl sulfoxide (DMSO), dimethyl formamide or toluene.
3. synthetic method according to claim 1, is characterized in that: described inert nitrogen gas or argon gas.
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