CN105439965B - The synthetic method of quinoxaline heterocycle and its derivative - Google Patents
The synthetic method of quinoxaline heterocycle and its derivative Download PDFInfo
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- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 title claims abstract description 18
- 238000010189 synthetic method Methods 0.000 title claims abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 76
- ISAOCJYIOMOJEB-UHFFFAOYSA-N benzoin Chemical compound C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1 ISAOCJYIOMOJEB-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000003054 catalyst Substances 0.000 claims abstract description 14
- 235000000126 Styrax benzoin Nutrition 0.000 claims abstract description 10
- 150000004985 diamines Chemical class 0.000 claims abstract description 9
- 244000028419 Styrax benzoin Species 0.000 claims abstract description 7
- 235000008411 Sumatra benzointree Nutrition 0.000 claims abstract description 7
- 229960002130 benzoin Drugs 0.000 claims abstract description 7
- 235000019382 gum benzoic Nutrition 0.000 claims abstract description 7
- 230000001590 oxidative effect Effects 0.000 claims abstract description 7
- 239000007800 oxidant agent Substances 0.000 claims abstract description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000006227 byproduct Substances 0.000 claims abstract description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical group CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 69
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Chemical group [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 claims description 46
- 238000009833 condensation Methods 0.000 claims description 5
- 230000005494 condensation Effects 0.000 claims description 5
- 239000003513 alkali Substances 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 238000007363 ring formation reaction Methods 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 239000007810 chemical reaction solvent Substances 0.000 claims 1
- 125000002541 furyl group Chemical group 0.000 claims 1
- 150000007529 inorganic bases Chemical class 0.000 claims 1
- 125000004076 pyridyl group Chemical group 0.000 claims 1
- 125000001544 thienyl group Chemical group 0.000 claims 1
- 239000000047 product Substances 0.000 abstract description 21
- 238000000034 method Methods 0.000 abstract description 7
- 229910052751 metal Inorganic materials 0.000 abstract description 5
- 239000002184 metal Substances 0.000 abstract description 5
- 238000007254 oxidation reaction Methods 0.000 abstract description 5
- 230000003647 oxidation Effects 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000006482 condensation reaction Methods 0.000 abstract description 2
- 239000011261 inert gas Substances 0.000 abstract description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 abstract 1
- 238000011084 recovery Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 78
- 238000000926 separation method Methods 0.000 description 40
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 20
- 238000005160 1H NMR spectroscopy Methods 0.000 description 20
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 20
- 238000012544 monitoring process Methods 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- LRRQSCPPOIUNGX-UHFFFAOYSA-N 2-hydroxy-1,2-bis(4-methoxyphenyl)ethanone Chemical compound C1=CC(OC)=CC=C1C(O)C(=O)C1=CC=C(OC)C=C1 LRRQSCPPOIUNGX-UHFFFAOYSA-N 0.000 description 12
- GEYOCULIXLDCMW-UHFFFAOYSA-N 1,2-phenylenediamine Chemical compound NC1=CC=CC=C1N GEYOCULIXLDCMW-UHFFFAOYSA-N 0.000 description 8
- OYTKINVCDFNREN-UHFFFAOYSA-N amifampridine Chemical compound NC1=CC=NC=C1N OYTKINVCDFNREN-UHFFFAOYSA-N 0.000 description 8
- PYHXGXCGESYPCW-UHFFFAOYSA-N diphenylacetic acid Chemical compound C=1C=CC=CC=1C(C(=O)O)C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-N 0.000 description 7
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 6
- ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical compound NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 0.000 description 6
- ZWVHTXAYIKBMEE-UHFFFAOYSA-N 2-hydroxyacetophenone Chemical class OCC(=O)C1=CC=CC=C1 ZWVHTXAYIKBMEE-UHFFFAOYSA-N 0.000 description 4
- DGRGLKZMKWPMOH-UHFFFAOYSA-N 4-methylbenzene-1,2-diamine Chemical compound CC1=CC=C(N)C(N)=C1 DGRGLKZMKWPMOH-UHFFFAOYSA-N 0.000 description 4
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 4
- AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 description 4
- 229910052723 transition metal Inorganic materials 0.000 description 4
- 150000003624 transition metals Chemical class 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 235000015511 Liquidambar orientalis Nutrition 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 241000736148 Styrax Species 0.000 description 3
- 239000004870 Styrax Substances 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 125000000217 alkyl group Chemical group 0.000 description 3
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 150000003216 pyrazines Chemical class 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 150000005361 3-phenylpyridines Chemical class 0.000 description 2
- BHHMPZQRVWVAAR-UHFFFAOYSA-N 7-bromo-8-methylpyrido[2,3-b]pyrazine Chemical compound C1=CN=C2C(C)=C(Br)C=NC2=N1 BHHMPZQRVWVAAR-UHFFFAOYSA-N 0.000 description 2
- USDIRSJFHPHMAS-UHFFFAOYSA-N ClC1=NC=C(C=2C1=NC=CN=2)F Chemical compound ClC1=NC=C(C=2C1=NC=CN=2)F USDIRSJFHPHMAS-UHFFFAOYSA-N 0.000 description 2
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 150000001345 alkine derivatives Chemical class 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- -1 dicarbonyl compound Chemical group 0.000 description 2
- AUJXLBOHYWTPFV-UHFFFAOYSA-N levomycin Chemical compound CN1C(=O)C(C)NC(=O)C(NC(=O)C=2N=C3C=CC=CC3=NC=2)COC(=O)C(C(C)C)N(C)C(=O)C2N(C)C(=O)C(C)NC(=O)C(NC(=O)C=3N=C4C=CC=CC4=NC=3)COC(=O)C(C(C)C)N(C)C(=O)C1CSC2SC AUJXLBOHYWTPFV-UHFFFAOYSA-N 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 150000003222 pyridines Chemical class 0.000 description 2
- TYLGVQVJCVFREB-UHFFFAOYSA-N pyrido[3,4-b]pyrazine Chemical compound C1=NC=CC2=NC=CN=C21 TYLGVQVJCVFREB-UHFFFAOYSA-N 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- RSNQVABHABAKEZ-UHFFFAOYSA-N 2,3-diphenylquinoxaline Chemical class C1=CC=CC=C1C1=NC2=CC=CC=C2N=C1C1=CC=CC=C1 RSNQVABHABAKEZ-UHFFFAOYSA-N 0.000 description 1
- KPGPIQKEKAEAHM-UHFFFAOYSA-N 2-chloro-3-phenylquinoxaline Chemical class ClC1=NC2=CC=CC=C2N=C1C1=CC=CC=C1 KPGPIQKEKAEAHM-UHFFFAOYSA-N 0.000 description 1
- QWNCDHYYJATYOG-UHFFFAOYSA-N 2-phenylquinoxaline Chemical class C1=CC=CC=C1C1=CN=C(C=CC=C2)C2=N1 QWNCDHYYJATYOG-UHFFFAOYSA-N 0.000 description 1
- XLVXYKCXPXIGEB-UHFFFAOYSA-N 6-methyl-2,3-diphenylquinoxaline Chemical class C=1C=CC=CC=1C1=NC2=CC(C)=CC=C2N=C1C1=CC=CC=C1 XLVXYKCXPXIGEB-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- AUJXLBOHYWTPFV-BLWRDSOESA-N CS[C@H]1SC[C@H]2N(C)C(=O)[C@@H](C)NC(=O)[C@H](COC(=O)[C@@H](C(C)C)N(C)C(=O)[C@@H]1N(C)C(=O)[C@@H](C)NC(=O)[C@H](COC(=O)[C@@H](C(C)C)N(C)C2=O)NC(=O)c1cnc2ccccc2n1)NC(=O)c1cnc2ccccc2n1 Chemical compound CS[C@H]1SC[C@H]2N(C)C(=O)[C@@H](C)NC(=O)[C@H](COC(=O)[C@@H](C(C)C)N(C)C(=O)[C@@H]1N(C)C(=O)[C@@H](C)NC(=O)[C@H](COC(=O)[C@@H](C(C)C)N(C)C2=O)NC(=O)c1cnc2ccccc2n1)NC(=O)c1cnc2ccccc2n1 AUJXLBOHYWTPFV-BLWRDSOESA-N 0.000 description 1
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 108010009858 Echinomycin Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229930183665 actinomycin Natural products 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium chloride Substances Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 229960004012 amifampridine Drugs 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- JHXKRIRFYBPWGE-UHFFFAOYSA-K bismuth chloride Chemical compound Cl[Bi](Cl)Cl JHXKRIRFYBPWGE-UHFFFAOYSA-K 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000010985 leather Substances 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical group [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- YEYHFKBVNARCNE-UHFFFAOYSA-N pyrido[2,3-b]pyrazine Chemical compound N1=CC=NC2=CC=CN=C21 YEYHFKBVNARCNE-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
- C07D241/42—Benzopyrazines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to carbon atoms of the hetero ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D241/12—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention provides the synthetic methods of a kind of quinoxaline heterocycle and its derivative, and quinoxaline heterocycle and its derivative are prepared through air oxidation, one step of cyclized condensation reaction under nontransition metal catalyst by benzoin and its derivatives and ortho position diamines.This method using benzoin and its derivatives cheap and easy to get be raw material, water-soluble nontransition metal catalyst and conveniently, economic, safety air be direct oxidant; one-step synthesis obtains target heterocyclic compound under conditions of room temperature or a little higher than room temperature; reaction condition is simply mild; inert gas shielding is proceeded without under air; it is easily operated; unique by-product is water; product separating-purifying is simple; the rate of recovery is high; reaction condition requirement is than relatively low; it is applied widely, there is good research and prospects for commercial application.
Description
Technical field
The invention belongs to the field of chemical synthesis, and in particular to benzoin and its derivatives are with ortho position diamines in nontransition metal
Under catalyst through under air aerobic oxidation, condensation and cyclization directly prepare the synthesis side of quinoxaline heterocycle and its derivative
Method.
Background technology
Substituted quinoxaline heterocycle and its derivative have very wide a pharmaceutical activity and biochemical activity, such as antibiotic activity,
Middle levomycin, echinomycin, actinomycin are blue for inhibiting leather（Family name）Positive bacteria growth is simultaneously active etc. to transplanted tumor.
Therefore these Hete rocyclic derivatives are played an important role pharmaceutical synthesis and bio-pharmaceuticals etc. are multi-field, are a kind of to have very much city
The medicine intermediate of field prospect.Quinoxaline heterocycle is generally by activity higher adjacent dicarbonyl compound or α-halogenatedcarbonylcompounds
It carries out condensation reaction acquisition at high temperature with ortho position diamines or passes through CAN, HF, BiCl3、AlCl3Catalyst action is compared with low temperature
The lower reaction of degree obtains.But adjacent dicarbonyl compound and α-halogenatedcarbonylcompounds are more active, it is unstable it is perishable, be not easy to store up
It deposits, therefore alternative need to be found.Also there are document report alkynes and ortho position diamines adding under transition metal-catalyzed in recent years
Annellated method for oxidation, but alkynes price is too high, hardly possible expands reaction scale, and reaction will use transition-metal catalyst and oxygen
Agent it is difficult to which transition metal is avoided to remain and generates discarded object, therefore is not very practical preparation method.Hydroxy-ketone such as styrax
And its derivative is simple and easy to get, is easily reacted and obtained by classical benzoic conden-sation, therefore uses hydroxyl ketone chemical combination
Object is a kind of relatively good strategy for raw material.Known generally with manganese dioxide is oxidant, but also generates the discarded object of manganese.
Therefore, exploitation is participated in using hypotoxicity, avirulent catalyst even without transition metal, in mildly simple item
The benzoin and its derivatives carried out under part prepare the non-constant value of method of quinoxaline heterocycle and its derivative with ortho position diamine reactant
It must study.
The content of the invention
The purpose of the present invention is：The synthetic method of a kind of quinoxaline heterocycle and its derivative is provided, with neighbour cheap and easy to get
Hydroxy-ketone such as benzoin and its derivatives are raw material, and water-soluble nontransition metal catalyst, air is oxidant, simple condition
Lower and ortho position diamines direct cyclizative condensation, oxidation reaction synthesizing quinoxaline heterocycle and its derivative, environmental pollution is small, it is efficient,
Convenience, safety, green.
The present invention technical solution be：By benzoin and its derivatives and ortho position diamines in nontransition metal catalyst
Direct reaction prepares quinoxaline heterocycle and its derivative under catalysis, it is characterized in that：Catalyst is water-soluble inorganic alkali, and air is oxygen
Agent, styrax or derivatives thereof and ortho position diamines direct oxidation condensation and cyclization synthesizing quinoxaline heterocycle and its derivative under air
Object, reaction temperature are room temperature ~ 120oC, when the reaction time is 12 ~ 48 small, unique by-product is water；
Wherein：
R1、R2It is that various functional groups are substituted in all kinds of substituted aryls of 2-, 3- or 4-, all kinds of substituted heteroaryls or each
Kind carbon chain lengths and the alkyl or hydrogen of branch substitution；
R3、R4Be various carbon chain lengths and branch substitution alkyl or hydrogen or be linked to be into closed-loop system in 2-, 3-,
Or 4- various substituted phenyl ring, heteroaryls；
Reaction dissolvent is benzene, DMSO, acetonitrile, THF, toluene, dimethylbenzene, DMF, alcohol or water；
Base catalyst is Li2CO3、K2CO3、Na2CO3、Cs2CO3、KHCO3、NaHCO3、CH3COOK、 K3PO4 .3H2O、
LiOH、NaOH、KOH、CsOH、t-BuONa、t-BuOK；1 ~ 200 mol% of dosage of alkali.
Wherein, react air to carry out, be oxidant directly using air.
Wherein, reaction temperature is room temperature ~ 100oC, when the time is 12 ~ 36 small.
Wherein, when the reaction time is 24 small.
Wherein, R1、R2Be various functional groups be substituted in all kinds of substituted aryls of 2-, 3- or 4-, all kinds of substituted heteroaryls or
It is various carbon chain lengths and the alkyl or hydrogen of branch substitution；
Wherein, reaction dissolvent DMSO.
Wherein, the catalyst is CsOH.
Wherein, the dosage of alkali used is 5-50 mol%.
It is an advantage of the invention that：1st, without using any transition-metal catalyst and ligand in reacting；2nd, reaction is in air
It carries out, it is oxidant that air is directly used without inert gas shielding；3rd, the base catalyst used can be directly commercially available；4、
This method compared with other methods reported in document, using styrax cheap and easy to get or derivatives thereof be raw material, mild condition,
Easily operated, reaction uses a small amount of organic solvent, and relatively environment-friendly green, the requirement to reaction condition is low, applied widely, and
Perception method has and potential is widely applied prospect compared to the obvious advantage.
Specific embodiment
The technical solution further illustrated the present invention with reference to specific embodiment, it will help understand the present invention,
But it is not restricted to present disclosure.
Embodiment 1：Diphenylhydroxyethanone and o-phenylenediamine prepare 2,3- diphenylquinoxalines, and reaction equation is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, and o-phenylenediamine (0.75 mmol, 1.5
Equiv.) and diphenylhydroxyethanone (0.106g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, in addition normal pressure
Air balls, at room temperature（30oC ）React 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 72%.1H NMR (500 MHz,
CDCl3): δ8.20 (dd, J = 3.5 Hz, J = 6.5 Hz, 2H), 7.75 (dd, J = 3.5 Hz, J = 6.5
Hz, 2H), 7.55 (d, J = 8.0 Hz, 4H), 7.38-7.32 (m, 6H). 13C NMR (125.4 MHz,
CDCl3): δ 153.3, 141.1, 139.0, 129.8, 129.7, 129.1, 128.7, 128.1. MS (EI): m/
z (%) 282 (96), 281 (100), 207 (33), 179 (34), 178 (30), 152 (15), 151 (15),
147 (13), 141 (11), 140 (15), 77 (13), 76 (22), 73 (39), 50 (14).
Embodiment 2：Diphenylhydroxyethanone and 3,4- diaminotoluene prepare 6- methyl -2,3- diphenylquinoxalines, reaction equation
It is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, 3,4- diaminotoluenes (0.75 mmol,
1.5 equiv.) and diphenylhydroxyethanone (0.106g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, in addition
Atmospheric air ball, at room temperature（30oC ）Reaction is for 24 hours.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 73%.1H NMR (500 MHz,
CDCl3): δ8.07 (d, J = 8.5 Hz, 1H), 7.96 (s, 1H), 7.59 (d, J = 9.0 Hz, 1H),
7.52 (d, J = 8.0 Hz, 4H), 7.37-7.31 (m, 6H), 2.61 (s, 3H). 13C NMR (125.4 MHz,
CDCl3): δ153.2, 152.5, 141.2, 140.4, 139.6, 139.1, 132.2, 129.8, 129.7,
128.61, 128.58, 128.5, 128.1, 127.9, 21.8. MS (EI): m/z (%) 296 (100), 295
(91), 281 (11), 207 (15), 193 (17), 192 (21), 165 (20), 148 (12), 147 (11),
90 (11), 89 (32), 73 (12).
Embodiment 3：Diphenylhydroxyethanone and chloro- 1, the 2- phenylenediamines of 4- prepare chloro- 2, the 3- diphenylquinoxalines of 6-, and reaction equation is such as
Under：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, chloro- 1, the 2- phenylenediamines of 4- (0.75 mmol,
1.5 equiv.) and diphenylhydroxyethanone (0.106g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, in addition
Atmospheric air ball, at room temperature（30oC ）React 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 70%.1H NMR (500 MHz,
CDCl3): δ8.17 (d, J = 2.5 Hz, 1H), 8.10 (d, J = 9.0 Hz, 1H), 7.71-7.61 (m,
1H), 7.52 (d, J = 7.5 Hz, 4H), 7.39-7.32 (m, 6H). 13C NMR (125.4 MHz, CDCl3):δ154.2, 153.5, 141.4, 139.6, 138.7, 138.6, 135.6, 130.9, 130.3, 129.8, 129.7,
129.0, 128.9, 128.24, 128.23, 128.0. MS (EI): m/z (%) 316 (100), 315 (85),
281 (31), 213 (20), 207 (44), 202 (22), 178 (46), 177 (22), 151 (28), 110
(16), 77 (15), 75 (32), 73 (31).
Embodiment 4：Diphenylhydroxyethanone and 2,3- diamino-pyridine prepare 2,3- hexichol yl pyridines [2,3-b] pyrazine, reaction
Formula is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, 2,3- diamino-pyridines (0.75 mmol,
1.5 equiv.) and diphenylhydroxyethanone (0.106g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, in addition
Atmospheric air ball, is heated to 70oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 78%.1H NMR (500 MHz,
CDCl3): δ9.14-9.13 (m, 1H), 8.47 (d, J = 8.0 Hz, 1H), 7.67-7.65 (m, 1H), 7.60
(d, J = 7.0 Hz, 2H), 7.52 (d, J = 7.0 Hz, 2H), 7.35-7.26 (m, 6H). 13C NMR
(125.4 MHz, CDCl3): δ 156.2, 154.6, 153.9, 149.7, 138.4, 138.0, 136.0, 132.8,
130.1, 129.7, 129.3, 129.2, 128.3, 128.0, 125.1. MS (EI): m/z (%) 283 (100),
282 (86), 281 (12), 207 (19), 180 (29), 179 (45), 141 (13), 103 (16), 77
(23), 76 (14), 73 (13).
Embodiment 5：Diphenylhydroxyethanone and 3,4- diamino-pyridine prepare 3,4- hexichol yl pyridines [3,4-b] pyrazine, reaction
Formula is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, 3,4- diamino-pyridines (0.75 mmol,
1.5 equiv.) and diphenylhydroxyethanone (0.106g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, in addition
Atmospheric air ball, is heated to 70oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 74%.1H NMR (500 MHz,
CDCl3): δ 9.59 (s, 1H), 8.80 (d, J = 6.0 Hz, 1H), 7.97 (d, J = 6.0 Hz, 1H),
7.54-7.51 (m, 4H), 7.41-7.36 (m, 2H), 7.35-7.32 (m, 4H). 13C NMR (125.4 MHz,
CDCl3): δ157.8, 155.2, 154.4, 147.2, 143.5, 138.2, 136.2, 129.8, 129.7,
129.6, 129.3, 128.3, 121.2. MS (EI): m/z (%) 283 (100), 282 (68), 180 (28),
179 (38), 153 (12), 141 (11), 103 (25), 77 (13), 76 (12), 50 (19).
Embodiment 6：Diphenylhydroxyethanone and ethylenediamine prepare 2,3- xenyl pyrazines, and reaction equation is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, and ethylenediamine (0.75 mmol, 1.5
Equiv.) and diphenylhydroxyethanone (0.106g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, in addition normal pressure
Air balls are heated to 90oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 65%.1H NMR (500 MHz,
CDCl3): δ8.60 (s, 2H), 7.46 (dd, J = 1.5 Hz, J = 8.0 Hz, 4H), 7.34-7.28 (m,
6H). 13C NMR (125.4 MHz, CDCl3): δ152.8, 142.0, 138.6, 129.6, 128.6, 128.2. MS
(EI): m/z (%) 232 (85), 231 (100), 204 (9), 177 (6), 176 (6), 116 (5), 115
(9), 104 (8), 103 (72), 102 (7), 77 (7), 76 (21). This compound was known:
Fan, L.; Chen, W.; Qian, C. Tetrahedron Letters, 2013, 54, 231-234.
Embodiment 7：Diphenylhydroxyethanone and 1,2- propane diamine prepare 5- methyl -2,3- xenyl pyrazines, and reaction equation is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, and 1,2- propane diamine (0.75 mmol, 1.5
Equiv.) and diphenylhydroxyethanone (0.106g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, in addition normal pressure
Air balls are heated to 90oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 59%.1H NMR (500 MHz,
CDCl3): δ 8.47 (s, 1H), 7.44-7.40 (m, 4H), 7.30-7.25 (m, 6H), 2.65 (s, 3H).13C NMR (125.4 MHz, CDCl3): δ151.5, 151.1, 149.7, 141.8, 138.8, 138.7, 129.6,
129.5, 128.4, 128.21, 128.17, 128.1, 21.3. MS (EI): m/z (%) 246 (81), 245
(100), 218 (8), 177 (7), 176 (7), 123 (6), 104 (12), 103 (53), 89 (7), 77
(8), 76 (22).
Embodiment 8：Anisoin and o-phenylenediamine prepare 2,3- (4- methoxyphenyls) quinoxaline, and reaction equation is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, and o-phenylenediamine (0.75 mmol, 1.5
Equiv.) and anisoin (0.136g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, in addition normal pressure is empty
Balloon is heated to 90oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 75%.1H NMR (500 MHz,
CDCl3): δ 8.12 (dd, J = 3.5 Hz, J = 6.5 Hz, 2H), 7.70 (dd, J = 3.5Hz, J = 6.0
Hz, 2H), 7.50 (d, J = 9.0 Hz, 4H), 6.87 (d, J = 8.5 Hz, 4H), 3.81 (s, 6H). 13C NMR (125.4 MHz, CDCl 3): δ 160.1, 152.9, 141.0, 131.7, 131.2, 129.4, 128.9, 113.7,
55.2. MS (EI): m/z (%) 342 (100), 341 (38), 327 (31), 311 (31), 299 (10), 281
(20), 209 (17), 208 (11), 207 (38), 171 (12), 166 (19), 133 (17), 73 (16).
Embodiment 9：Anisoin and 3,4- diaminotoluene prepare 2,3- (4- methoxyphenyls) -6- methyl-quinoxalines,
Reaction equation is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, 3,4- diaminotoluenes (0.75 mmol,
1.5 equiv.) and anisoin (0.136g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, in addition normal
Air balls are pressed, are heated to 90oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 76%.1H NMR (500 MHz,
CDCl3): δ8.00 (d, J = 8.5 Hz, 1H), 7.89 (s, 1H), 7.54 (dd, J = 2.0 Hz, J =
8.5 Hz, 1H), 7.48 (dd, J = 2.5 Hz, J = 9.0 Hz, 4H), 6.86 (d, J = 9.0 Hz, 4H),
3.81 (s, 6H), 2.58 (s, 3H). 13C NMR (125.4 MHz, CDCl3): δ160.03, 159.98,
152.8,152.1, 141.1, 139.9, 139.5, 131.86, 131.85, 131.7, 131.2, 131.1, 128.5,
127.8, 113.68, 113.66, 55.2, 21.8. MS (EI): m/z (%) 356 (26), 355 (25), 341
(29), 282 (21), 208 (21), 207 (100), 202 (22), 191 (15), 147 (26), 133 (14),
73 (78).
Embodiment 10：Anisoin and chloro- 1, the 2- phenylenediamines of 4- prepare 2,3- (4- methoxyphenyls) -6- chloro-quinoxalines,
Reaction equation is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, chloro- 1, the 2- phenylenediamines of 4- (0.75 mmol,
1.5 equiv.) and anisoin (0.136g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, in addition normal
Air balls are pressed, are heated to 90oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 80%.1H NMR (500 MHz,
CDCl3): δ 8.10 (d, J = 2.0 Hz, 1H), 8.03 (d, J = 8.5 Hz, 1H), 7.63 (dd, J =
2.5 Hz, J = 8.0 Hz, 1H), 7.48 (dd, J = 2.5 Hz, J = 9.0 Hz, 4H), 6.87 (d, J =
8.5 Hz), 3.82 (s, 6H). 13C NMR (125.4 MHz, CDCl3): δ160.4, 160.3, 153.7,
153.1, 131.3, 131.23, 131.21, 131.16, 130.3, 130.1, 127.8, 113.8, 113.7,
55.2. MS (EI): m/z (%) 376 (100), 375 (29), 361 (30), 345 (35), 281 (28), 208
(21), 207 (49), 202 (18), 200 (19), 133 (34), 103 (16), 73 (33).
Embodiment 11：Anisoin and 3,4- diamino-pyridines prepare 2,3- (4- methoxyphenyls) pyrido [3,4-b]
Pyrazine, reaction equation are as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, 3,4- diamino-pyridines (0.75 mmol,
1.5 equiv.) and anisoin (0.136g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, in addition normal
Air balls are pressed, are heated to 90oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 83%.1H NMR (500 MHz,
CDCl3): δ 9.51(s, 1H), 8.74 (d, J = 5.5 Hz, 1H), 7.90 (d, J = 5.5 Hz, 1H),
7.53-7.49 (m, 4H), 6.87 (dd, J = 3.0 Hz, J = 9.0 Hz, 4H), 3.82 (s, 6H). 13C
NMR (125.4 MHz, CDCl3): δ F160.9, 160.6, 157.3, 154.8, 154.1, 146.8, 143.4,
136.1, 131.4, 131.2, 130.9, 130.8, 121.1, 113.85, 113.84, 55.3. MS (EI): m/z
(%) 344 (27), 343 (100), 342 (23), 328 (28), 312 (41), 281 (25), 210 (20),
209 (13), 208 (11), 207 (45), 181 (10), 167 (12), 133 (35), 103 (14), 73
(18).
Embodiment 12：Anisoin and ethylenediamine prepare 5,6- (4- methoxyphenyls) -2,3- dihydro pyrazines, and reaction equation is such as
Under：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, and ethylenediamine (0.75 mmol, 1.5
Equiv.) and anisoin (0.136g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, in addition normal pressure is empty
Balloon is heated to 90oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 61%.1H NMR (500 MHz,
CDCl3): δ7.29 (d, J = 8.5 Hz, 4H), 6.69 (d, J = 8.5 Hz, 4H), 3,69 (s, 6H),
3.56 (s, 4H). 13C NMR (125.4 MHz, CDCl3): δ 160.6, 159.5, 130.5, 129.5, 113.4,
55.1, 45.7. MS (EI): m/z (%) 294 (17), 293 (9), 134 (11), 133 (100), 103
(10), 90 (8), 77 (5).
Embodiment 13：Anisoin and 1,2- propane diamine prepare 2,3- (4- methoxyphenyls) -5- methylpyrazines, reaction equation
It is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, and 1,2- propane diamine (0.75 mmol, 1.5
Equiv.) and anisoin (0.136g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, in addition normal pressure is empty
Balloon is heated to 90oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 65%.1H NMR (500 MHz,
CDCl3): δ 8.39 (s, 1H), 7.40-7.36 (m, 4H), 6.84-6.83 (m, 4H), 3.80 (s, 6H),
2.62 (s, 3H). 13C NMR (125.4 MHz, CDCl3): δ 159.8, 159.7, 150.9, 150.4, 149.1,
141.2, 131.5, 131.4, 130.9, 130.8, 113.74, 113.68, 55.2, 21.2. MS (EI): m/z
(%) 306 (100), 305 (57), 291 (23), 275 (14), 263 (15), 262 (10), 133 (45),
103 (19), 90 (15).
Embodiment 14：2- hydroxy acetophenones and o-phenylenediamine prepare 2- phenyl quinoxalines, and reaction equation is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, and o-phenylenediamine (0.75 mmol, 1.5
Equiv.) and 2- hydroxy acetophenones (0.068g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, in addition normal
Air balls are pressed, are heated to 90oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 78%.1H NMR (500 MHz,
CDCl3): δ9.28 (s, 1H), 8.17-8.08 (m, 4H), 7.74-7.67 (m, 2H), 7.54-7.46 (m,
3H). 13C NMR (125.4 MHz, CDCl3): δ151.6, 143.1, 142.1, 141.4, 136.6, 130.03,
129.98, 129.5, 129.3, 128.97,128.94, 127.37. MS (EI): m/z (%) 206 (100), 205
(9), 180 (5), 179 (36), 178 (15), 152 (6), 151 (5), 103 (13), 77 (6), 76
(18), 70 (6), 61 (6), 50 (8).
Embodiment 15：2- hydroxy acetophenones and chloro- 1, the 2- phenylenediamines of 4- prepare the chloro- 2- phenyl quinoxalines of 7-, and reaction equation is such as
Under：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, chloro- 1, the 2- phenylenediamines of 4- (0.75 mmol,
1.5 equiv.) and 2- hydroxy acetophenones (0.068g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, is added
Upper atmospheric air ball, is heated to 90oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 72%.1H NMR (500 MHz,
CDCl3): δ 9.30 (s, 1H), 8.19-8.14 (m, 3H), 8.04 (d, J = 9.0Hz, 1H), 7.67 (d,J = 9.0 Hz, 1H), 7.58-7.53 (m, 3H). 13C NMR (125.4 MHz, CDCl3): δ152.5, 143.4,
142.6, 140.1, 136.3, 136.1, 130.52, 130.46, 130.3, 129.2, 128.5, 127.6. MS
(EI): m/z (%) 240 (100), 213 (21), 205 (14), 178 (29), 177 (9), 151 (10), 120
(9), 110 (12), 75 (17), 63 (10), 61 (8).
Embodiment 16：2- hydroxy acetophenones and 2,3 diamino pyridine prepare 3- phenylpyridines simultaneously [2,3-b] pyrazine, reaction
Formula is as follows：
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, 2,3- diamino-pyridines (0.75 mmol,
1.5 equiv.) and 2- hydroxy acetophenones (0.068g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, is added
Upper atmospheric air ball, is heated to 90oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 69%.1H NMR (500 MHz,
CDCl3): δ9.41 (s, 1H), 9.14 (dd, J = 2.0 Hz, J = 4.5 Hz, 1H), 8.42 (dd, J =
2.0 Hz, J = 8.5 Hz, 1H), 8.30 (dd, J = 2.0 Hz, J = 8.0 Hz, 2H), 7.65 (dd, J =
4.0 Hz, J = 8.0 Hz, 1H), 7.55-7.48 (m, 3H). 13C NMR (125.4 MHz, CDCl3): δ
154.5, 154.3, 150.7, 144.2, 138.0, 136.7, 135.6, 130.9, 129.1, 127.9, 124.6.
MS (EI): m/z (%) 208 (11), 207 (72), 180 (16), 179 (26), 104 (28), 103 (14),
92 (50), 91 (80), 88 (33), 77 (22), 73 (42), 70 (100), 61 (98).
Embodiment 17：2- hydroxy acetophenones and 3,4- diamino-pyridines prepare 3- phenylpyridines simultaneously [3,4-b] pyrazine, reaction
Formula is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, 3,4- diamino-pyridines (0.75 mmol,
1.5 equiv.) and 2- hydroxy acetophenones (0.068g, 0.5 mmol), DMSO (1.0 mL) is added as solvent, is added
Upper atmospheric air ball, is heated to 90oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 70%.1H NMR (500 MHz,
CDCl3): δ 9.53 (s, 1H), 9.41 (s, 1H), 8.82 (d, J = 6.0 Hz, 1H), 8.22-8.20 (m,
2H), 7.95 (d, J = 6.0 Hz, 1H), 7.59-7.57 (m, 3H). 13C NMR (125.4 MHz, CDCl3):δ 155.8, 154.2, 147.7, 145.0, 144.9, 136.7, 135.8, 131.3, 129.3, 128.0,
121.8. MS (EI): m/z (%) 207 (100), 206 (7), 180 (24), 179 (19), 153 (6), 104
(16), 103 (15), 102 (9), 77 (11), 76 (9), 50 (12). HRMS calcd for C13H10N3 ([M+
H]+): 208.0869; found: 208.0882.
Embodiment 18：1,2- (4- chlorphenyls) -2- hydroxyethanones and o-phenylenediamine prepare 2,3- (4- chlorphenyls) quinoxaline,
Reaction equation is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, and o-phenylenediamine (0.75 mmol, 1.5
Equiv.) and 1,2- (4- chlorphenyls) -2- hydroxyethanones (0.141g, 0.5 mmol), DMSO (1.0 mL) is added
For solvent, in addition atmospheric air ball, is heated to 70oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 79%.1H NMR (500 MHz,
CDCl3): δ 8.17-8.13 (m, 2H), 7.80-7.77 (m, 2H), 7.48-7.46 (m, 4H), 7.35-7.33
(m, 4H). 13C NMR (125.4 MHz, CDCl3): δ 151.9, 141.2, 137.2, 135.3, 131.1,
130.3, 129.2, 128.7. MS (EI): m/z (%) 350 (100), 349 (63), 315 (74), 207
(54), 178 (84), 151 (36), 76 (72), 75 (32), 73 (48), 50 (40)
Embodiment 19：1,2- (4- chlorphenyls) -2- hydroxyethanones and 2,3 diamino pyridine prepare 2,3- (4- chlorphenyls)
Pyrido [2,3-b] pyrazine, reaction equation is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, 2,3- diamino-pyridines (0.75 mmol,
1.5 equiv.) and 1,2- (4- chlorphenyls) -2- hydroxyethanones (0.141g, 0.5 mmol), add DMSO (1.0
ML it is) solvent, in addition atmospheric air ball, is heated to 90oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 86%.1H NMR (500 MHz,
CDCl3): δ 9.14-9.13 (m, 1H), 8.45-8.42 (m, 1H), 7.70-7.67 (m, 1H), 7.53-7.51
(m, 2H), 7.46-7.45 (m, 2H), 7.32-7.26 (m, 4H). 13C NMR (125.4 MHz, CDCl3): δ
154.6, 154.3, 153.0, 149.5, 138.0, 136.5, 136.1, 136.0, 135.7, 131.4, 131.2,
131.0, 128.7, 128.5, 125.4. MS (EI): m/z (%) 351 (61), 349 (54), 291 (40),
281 (24), 251 (29), 207 (42), 205 (63), 204 (46), 203 (24), 202 (43), 176
(17), 165 (100), 164 (16), 163 (22), 73 (33). HRMS calcd for C19H12Cl2N3 ([M+H
]+): 352.0403; found: 352.0413.
Embodiment 20：1,2- (4- chlorphenyls) -2- hydroxyethanones and 3,4- diamino-pyridines prepare 2,3- (4- chlorphenyls)
Pyrido [3,4-b] pyrazine, reaction equation is as follows：
,
Sequentially add CsOH (0.0126g, 15 mol%) in reaction tube, 3,4- diamino-pyridines (0.75 mmol,
1.5 equiv.) and 1,2- (4- chlorphenyls) -2- hydroxyethanones (0.141g, 0.5 mmol), add DMSO (1.0
ML it is) solvent, in addition atmospheric air ball, is heated to 90oC reacts 24 h.
TLC monitorings are after the reaction was complete, and product is purified with pillar layer separation, separation yield 82%.1H NMR (500 MHz,
CDCl3): δ 9.53 (s, 1H), 8.79 (d, J = 6.0 Hz, 1H), 7.92 (d, J = 6.0 Hz, 1H),
7.47-7.44 (m, 4H), 7.33 (d, J = 8.5 Hz, 4H). 13C NMR (125.4 MHz, CDCl3): δ
156.2, 154.3, 153.6, 147.5, 143.4, 136.3, 136.2, 136.0, 135.9, 131.1, 131.0,
128.8, 121.1. MS (EI): m/z (%) 351 (100), 349 (86), 291 (31), 281 (22), 251
(36), 207 (31), 205 (41), 204 (25), 203 (24), 202 (50), 165 (60), 73 (28).
HRMS calcd for C19H12Cl2N3 ([M+H]+): 352.0403; found: 352.0418。
Claims (1)
1. the synthetic method of quinoxaline heterocycle and its derivative, direct under air by benzoin and its derivatives and ortho position diamines
Oxidative condensation Cyclization quinoxaline heterocycle and its derivative, unique by-product are water；
It is characterized in that：R1, R2 be various functional groups be substituted in 2-, 3- or 4- phenyl, furyl, thienyl, pyridyl group；
R3, R4 be carbon atom adjacent thereto be linked to be closed-loop system in 2-, 3- or 4- various substituted phenyl ring, heteroaryls；Reaction
Solvent is DMSO；The water-soluble inorganic base catalyst is CsOH, 1 ~ 200 mol% of dosage of alkali；Reaction carries out under air,
It is oxidant directly using air；Reaction temperature is room temperature ~ 120oC, when the reaction time is 12 ~ 36 small.
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