CN104447536B - Preparation method of N-2-quinolyl aryl sulfonamide compounds - Google Patents
Preparation method of N-2-quinolyl aryl sulfonamide compounds Download PDFInfo
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- CN104447536B CN104447536B CN201410579457.2A CN201410579457A CN104447536B CN 104447536 B CN104447536 B CN 104447536B CN 201410579457 A CN201410579457 A CN 201410579457A CN 104447536 B CN104447536 B CN 104447536B
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- compound
- quinoline
- sulfonic acid
- acid amides
- aryl sulfonic
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- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- GIIWGCBLYNDKBO-UHFFFAOYSA-N Quinoline 1-oxide Chemical class C1=CC=C2[N+]([O-])=CC=CC2=C1 GIIWGCBLYNDKBO-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 11
- 239000000654 additive Substances 0.000 claims abstract description 8
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 150000002497 iodine compounds Chemical class 0.000 claims abstract description 4
- 239000007800 oxidant agent Substances 0.000 claims abstract description 4
- 230000001590 oxidative effect Effects 0.000 claims abstract description 4
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- -1 aryl sulfonic acid Chemical compound 0.000 claims description 39
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 21
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 18
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 12
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Natural products P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 9
- 241001597008 Nomeidae Species 0.000 claims description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 7
- 230000000996 additive effect Effects 0.000 claims description 7
- 238000000926 separation method Methods 0.000 claims description 7
- 239000000741 silica gel Substances 0.000 claims description 7
- 229910002027 silica gel Inorganic materials 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 6
- DORMTBIPKNPJPY-UHFFFAOYSA-N acetic acid;iodobenzene Chemical compound CC(O)=O.IC1=CC=CC=C1 DORMTBIPKNPJPY-UHFFFAOYSA-N 0.000 claims description 6
- 230000003647 oxidation Effects 0.000 claims description 6
- 238000007254 oxidation reaction Methods 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- LMYRWZFENFIFIT-UHFFFAOYSA-N toluene-4-sulfonamide Chemical compound CC1=CC=C(S(N)(=O)=O)C=C1 LMYRWZFENFIFIT-UHFFFAOYSA-N 0.000 claims description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- QWKKYJLAUWFPDB-UHFFFAOYSA-N 4-nitrobenzenesulfonamide Chemical class NS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1 QWKKYJLAUWFPDB-UHFFFAOYSA-N 0.000 claims description 3
- 150000008424 iodobenzenes Chemical class 0.000 claims description 3
- 239000012046 mixed solvent Substances 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical class ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 2
- HHHDJHHNEURCNV-UHFFFAOYSA-N 4-chlorobenzenesulfonamide Chemical class NS(=O)(=O)C1=CC=C(Cl)C=C1 HHHDJHHNEURCNV-UHFFFAOYSA-N 0.000 claims description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical group COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 2
- 125000001033 ether group Chemical group 0.000 claims description 2
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 3
- AKSGZTOWWHUHEB-UHFFFAOYSA-N [N]=O.N1=CC=CC2=CC=CC=C12.N1=CC=CC2=CC=CC=C12 Chemical class [N]=O.N1=CC=CC2=CC=CC=C12.N1=CC=CC2=CC=CC=C12 AKSGZTOWWHUHEB-UHFFFAOYSA-N 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- SVDVKEBISAOWJT-UHFFFAOYSA-N n-methylbenzenesulfonamide Chemical compound CNS(=O)(=O)C1=CC=CC=C1 SVDVKEBISAOWJT-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 10
- 230000015572 biosynthetic process Effects 0.000 abstract description 8
- 238000003786 synthesis reaction Methods 0.000 abstract description 8
- 150000001875 compounds Chemical class 0.000 abstract description 4
- 125000004421 aryl sulphonamide group Chemical group 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 239000012847 fine chemical Substances 0.000 abstract description 2
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- 238000003889 chemical engineering Methods 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- XFJJGEIKODBFGJ-UHFFFAOYSA-N 4-methyl-n-quinolin-2-ylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC1=CC=C(C=CC=C2)C2=N1 XFJJGEIKODBFGJ-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000009432 framing Methods 0.000 description 3
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 3
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 2
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 2
- JNPGUXGVLNJQSQ-BGGMYYEUSA-M (e,3r,5s)-7-[4-(4-fluorophenyl)-1,2-di(propan-2-yl)pyrrol-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)N1C(C(C)C)=C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C1 JNPGUXGVLNJQSQ-BGGMYYEUSA-M 0.000 description 2
- VAVHMEQFYYBAPR-ITWZMISCSA-N (e,3r,5s)-7-[4-(4-fluorophenyl)-1-phenyl-2-propan-2-ylpyrrol-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound CC(C)C1=C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=CN1C1=CC=CC=C1 VAVHMEQFYYBAPR-ITWZMISCSA-N 0.000 description 2
- HIHOEGPXVVKJPP-JTQLQIEISA-N 5-fluoro-2-[[(1s)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyridine-3-carbonitrile Chemical compound N([C@@H](C)C=1N=CC(F)=CC=1)C(C(=CC=1F)C#N)=NC=1NC=1C=C(C)NN=1 HIHOEGPXVVKJPP-JTQLQIEISA-N 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- BMQYPTYCJLNXQP-UHFFFAOYSA-N n-(6-methoxyquinolin-2-yl)-4-methylbenzenesulfonamide Chemical compound C1=CC2=CC(OC)=CC=C2N=C1NS(=O)(=O)C1=CC=C(C)C=C1 BMQYPTYCJLNXQP-UHFFFAOYSA-N 0.000 description 2
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 1
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 1
- QKJAZPHKNWSXDF-UHFFFAOYSA-N 2-bromoquinoline Chemical compound C1=CC=CC2=NC(Br)=CC=C21 QKJAZPHKNWSXDF-UHFFFAOYSA-N 0.000 description 1
- YCMLQMDWSXFTIF-UHFFFAOYSA-N 2-methylbenzenesulfonimidic acid Chemical compound CC1=CC=CC=C1S(N)(=O)=O YCMLQMDWSXFTIF-UHFFFAOYSA-N 0.000 description 1
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- CXGAWPLDXXMJON-UHFFFAOYSA-N [N]=O.CC1=CC=NC2=CC=CC=C12 Chemical class [N]=O.CC1=CC=NC2=CC=CC=C12 CXGAWPLDXXMJON-UHFFFAOYSA-N 0.000 description 1
- SBCJZZMEBWLYDH-UHFFFAOYSA-N [N]=O.COC=1C=C2C=CC=NC2=CC1 Chemical class [N]=O.COC=1C=C2C=CC=NC2=CC1 SBCJZZMEBWLYDH-UHFFFAOYSA-N 0.000 description 1
- NIEVKYPIXJDDNI-UHFFFAOYSA-N [N]=O.N1=CC=CC2=CC=CC=C12 Chemical class [N]=O.N1=CC=CC2=CC=CC=C12 NIEVKYPIXJDDNI-UHFFFAOYSA-N 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
- KDFTZXJPBNANFN-UHFFFAOYSA-N ethyl n-[4-(6-methyl-1,3-benzothiazol-2-yl)phenyl]carbamate Chemical compound C1=CC(NC(=O)OCC)=CC=C1C1=NC2=CC=C(C)C=C2S1 KDFTZXJPBNANFN-UHFFFAOYSA-N 0.000 description 1
- AKPBXEIYIYWEFI-UHFFFAOYSA-N n-(trifluoromethyl)benzenesulfonamide Chemical compound FC(F)(F)NS(=O)(=O)C1=CC=CC=C1 AKPBXEIYIYWEFI-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the technical field of fine chemical engineering, and discloses a preparation method of N-2-quinolyl aryl sulfonamide compounds. The preparation method can be used for synthesizing a series of N-2-quinolyl aryl sulfonamide compounds from aryl sulfonamide and derivative of quinoline N-oxide by carrying out a heating reaction in an organic solvent with a trivalent iodine compound serving as an oxidant and triarylphosphine compounds functioning as additives. The invention mainly aims at providing a synthesis method of the N-2-quinolyl aryl sulfonamide compounds. The method is simple and efficient, high in atom economy and environment-friendly; the method has the advantages of being simple in method step, easy in obtaining of raw materials, high in atom economy, environment-friendly and the like. The N-2-quinolyl aryl sulfonamide, as an important skeleton structure, can be widely applied to the medicine synthesis field, and has high use value and social and economic benefits.
Description
Technical field
The present invention relates to a kind of preparation method of N-2- quinolyls arylsulfonamides compound, belongs to fine chemical technology
Field.
Background technology
N-2- quinolyl arylsulfonamides compounds be a class it is important with bioactive molecule, its framing structure frequency
It is numerous to come across in drug molecule, have a very wide range of applications in pharmaceutical synthesis field.With regard to N-2- quinolyl arylsulfonyls
The synthesis of aminated compoundss, generally adopts the following two kinds method:
(1) aryl sulfonic acid amides and 2- Bromoquinoline coupling reactions
The substrate of the method is expensive, need to be previously prepared, and environment is unfriendly, and Atom economy is low.[referring to:
Baffoe,Jonathan et al.Org.Lett.2010,12,1532.]。
(2) sulfonic acid chloride and 2- quinolin-2-ylamine coupling reactions
The substrate of the method is expensive, need to be previously prepared, and environment is unfriendly, and Atom economy is low.[referring to (a)
Uchikawa,Osamu et al.PCT Int.Appl.2008016131,07Feb 2008;(b)Edwards,Martin
Paul et al.PCT Int.Appl.,2005060963,07Jul 2005;(c)Jacobsen,Jennifer A.et
al.Journal of Medicinal Chemistry,2011,54,591-602;(d)Kokatla,Hari Prasad et
al.Org.Biomolecular Chemistry,2013,11,1179.]。
The content of the invention
In order to overcome the deficiencies in the prior art, it is an object of the present invention to provide a kind of N-2- quinolyls aryl sulfonic acid amides
The preparation method of class compound.The method has that method and step is simple, raw material is easy to get, Atom economy height, environmental friendliness etc. are excellent
Point.As N-2- quinolyl aryl sulfonic acid amides are the important framing structures of a class, have widely in pharmaceutical synthesis field
Using.
In order to realize foregoing invention purpose, in the presence of solving the problems, such as prior art, the technical scheme that the present invention takes
It is:A kind of preparation method of N-2- quinolyls arylsulfonamides compound, is spread out with aryl sulfonic acid amides and Quinoline N-Oxide
Biological is raw material, and with trivalent iodine compound as oxidant, triaryl phosphine compound is additive, is heated in organic solvent anti-
Should, synthesizing a series of N-2- quinolyls arylsulfonamides compounds, reaction equation is as follows:
In formula, the aryl sulfonic acid amides are selected from p-methylphenyl sulphonylamine, 4- chlorobenzene sulfonamides, 4- nitrobenzene sulfonamides or 4-
One kind in trifluoromethyl benzene sulfonamide;
The Quinoline N-Oxide derivant is selected from Quinoline N-Oxide, 4- methylquinolines nitrogen oxides or 6- methoxyl group quinolines
One kind in quinoline nitrogen oxides;
The one kind of iodonium compound oxidation agent in iodobenzene acetate or double (trifluoroacetyl epoxide) iodobenzenes;
The triaryl phosphine compound additive in triphenylphosphine or 4-N- morpholines-phenyl diphenylphosphine one
Kind;
The organic solvent is selected from ether, benzene, toluene, 1,4- dioxane, dimethyl sulfoxide, N, N- dimethyl formyls
Amine, methanol, ethanol, 1,2- dichloroethanes, n-butyl alcohol, dichloromethane, chloroform, hexamethylene, n-butyl ether, carbon tetrachloride, second
One or two mixed solvents in acetoacetic ester, petroleum ether, methyl tertiary butyl ether(MTBE), tetrahydrofuran, acetone or acetonitrile.
A kind of preparation method of N-2- quinolyls arylsulfonamides compound, comprises the following steps:
A () is by aryl sulfonic acid amides, Quinoline N-Oxide derivant, the agent of iodonium compound oxidation and triaryl phosphine chemical combination
Thing additive is added sequentially in the Schlenk bottles of 25mL, then add refined organic solvent be placed in oil bath it is anti-
Should, at 20-130 DEG C, the response time is controlled in 7-30 hours, the aryl sulfonic acid amides and Quinoline N-Oxide for reaction temperature control
The mol ratio of derivant is 1.0:1.0th, the mol ratio of the aryl sulfonic acid amides and iodonium compound oxidation agent is 1.0:0.5-
4.0th, the mol ratio of the aryl sulfonic acid amides and triaryl phosphine compound additive is 1.0:0.5-4.0, the organic solvent
Addition be 10-100 times of aryl sulfonic acid amides quality;
B () reaction terminates after, organic solvent is removed under reduced pressure;
C () is obtained series N-2- quinolyl arylsulfonamides using petrol ether/ethyl acetate eluting, Jing silica gel post separation
Compound.
Present invention has the advantages that:A kind of preparation method of N-2- quinolyls arylsulfonamides compound, is with aryl
Sulfonamide and Quinoline N-Oxide derivant are raw material, and with trivalent iodine compound as oxidant, triaryl phosphine compound is to add
Plus agent, reacting by heating, synthesizes a series of N-2- quinolyls arylsulfonamides compounds in organic solvent.With prior art phase
Than, the present invention be mainly to provide it is a kind of it is simple efficiently, Atom economy is high, eco-friendly N-2- quinolyls arylsulfonyl amination
The synthetic method of compound, the method have that method and step is simple, raw material is easy to get, Atom economy high, advantages of environment protection.By
It is the important framing structure of a class in N-2- quinolyl aryl sulfonic acid amides, has a very wide range of applications in pharmaceutical synthesis field,
With larger use value and economic results in society.
Description of the drawings
Fig. 1 is compound 1a's1H-NMR。
Fig. 2 is compound 1a's13C-NMR。
Fig. 3 is compound 1b's1H-NMR。
Fig. 4 is compound 1b's13C-NMR。
Fig. 5 is compound 1c's1H-NMR。
Fig. 6 is compound 1c's13C-NMR。
Fig. 7 is compound 1d's1H-NMR。
Fig. 8 is compound 1d's13C-NMR。
Fig. 9 is compound 1e's1H-NMR。
Figure 10 is compound 1e's13C-NMR。
Figure 11 is compound 1f's1H-NMR。
Figure 12 is compound 1f's13C-NMR。
Specific embodiment
With reference to embodiment, the invention will be further described:
Embodiment 1:The synthesis of 4-Methyl-N- (quinolin-2-yl) benzenesulfonamide (1a)
Accurately weigh p-methylphenyl sulphonylamine (42.8mg, 0.25mmol), Quinoline N-Oxide (36.3mg,
0.25mmol), iodobenzene acetate (40.1mg, 0.125mmol), triphenylphosphine (32.8mg, 0.125mmol), and be added sequentially to
In the Schlenk bottles of 25mL, refined acetonitrile (0.50mL), 20 DEG C of reaction 8h are added.After reaction terminates, it is removed under reduced pressure molten
Agent, using petrol ether/ethyl acetate as eluant, silica gel post separation, 4-Methyl-N- (quinolin-2-yl)
The yield of benzenesulfonamide is 80%.1H NMR(400MHz,CDCl3)δ11.86(s,1H),7.90–7.85(m,
3H), 7.63-7.60 (m, 2H), 7.46 (d, J=8.5Hz, 1H), 7.37-7.34 (m, 1H), 7.26 (d, J=5.8Hz, 2H),
6.95 (d, J=9.4Hz, 1H), 2.39 (s, 3H);13C NMR(101MHz,CDCl3)δ154.0,142.6,140.5,139.7,
136.3,131.5,129.2,127.9,126.1,124.5,121.2,120.9,117.2,21.3;IR(KBr)υ(cm-1)3425,
3337,3050,3024,1670,1601,1493,1475,1441,1382,1157,910,778,736,730,698;HRMS-EI
(m/z):[M+H]+Calculated for C16H14N2O2S,299.0854;found,299.0866.
Embodiment 2:The synthesis of 4-Nitro-N- (quinolin-2-yl) benzenesulfonamide (1c)
Accurately weigh 4- nitrobenzene sulfonamides (50.5mg, 0.25mmol), Quinoline N-Oxide (44.3mg,
0.25mmol), iodobenzene acetate (123.5mg, 0.5mmol), triphenylphosphine (17.9mg, 0.125mmol), and be added sequentially to
In the Schlenk bottles of 25mL, refined toluene (3.0mL) is added, is placed in 60 DEG C of oil baths and is reacted 7h.After reaction terminates, subtract
Pressure removes solvent, using petrol ether/ethyl acetate as eluant, silica gel post separation, 4-Nitro-N- (quinolin-2-yl)
The yield of benzenesulfonamide is 76%.1H NMR (400MHz, DMSO) δ 13.43 (s, 1H), 8.17 (d, J=
8.3Hz, 2H), 7.87 (d, J=7.9Hz, 1H), 7.74-7.70 (m, 1H), 7.64-7.57 (m, 5H), 7.44-7.40 (m,
1H);13C NMR(101MHz,DMSO)δ148.4,141.8,131.6,131.4,130.9,130.8,128.2,128.1,
127.7,126.9,123.9,123.7,114.8;IR(KBr)υ(cm-1)3439,3326,2960,2921,2865,1653,
1492,1395,1378,1092,1015,908,837,771,758,734;HRMS(EI)Calculated for
C15H11N3O4S329.0470[M+],found 329.0478.
Embodiment 3:The synthesis of 4-Methyl-N- (quinolin-2-yl) benzenesulfonamide (1d)
Accurately weigh p-methylphenyl sulphonylamine (42.8mg, 0.25mmol), 4- methylquinoline nitrogen oxides (50.5mg,
0.25mmol), iodobenzene acetate (40.1mg, 0.125mmol), triphenylphosphine (32.8mg, 0.125mmol), and be added sequentially to
In the Schlenk bottles of 25mL, acetonitrile (2.50mL) and toluene (2.50mL) mixed solvent, 20 DEG C of reaction 8h are added.Reaction terminates
Afterwards, removal of solvent under reduced pressure, using petrol ether/ethyl acetate as eluant, silica gel post separation, 4-Methyl-N-
(quinolin-2-yl) yield of benzenesulfonamide is 80%.White solid (62.4mg, 40%yield),
mp 225-227℃.1H-NMR(d6-DMSO,400MHz):12.90 (bs, 1H), 7.86 (d, J=8.0Hz, 1H), 7.80 (d, J
=7.5Hz, 2H), 7.68-7.65 (m, 1H), 7.56 (d, J=8.1Hz, 1H), 7.42 (s, 1H), 7.38-7.33 (m, 3H),
2.57(s,3H),2.34(s,3H);13C-NMR(d6-DMSO,101MHz):155.0,150.9,142.1,141.5,132.2,
129.8,126.6,125.5,124.4,121.6,118.8,118.2,115.4,21.4,19.7;IR(KBr)(cm-1)3442,
3198,2973,1629,1514,1396,1269,1138,908,838,677,615,555,475;HRMS-EI(m/z):[M]+
Calculated for C17H16N2O2S,312.0932;found,312.0930.
Embodiment 4:The conjunction of 4-Trifluoromethyl-N- (quinolin-2-yl) benzenesulfonamide (1e)
Into
Accurately weigh Quinoline N-Oxide (44.3mg, 0.25mmol), 4- trifluoromethyl benzene sulfonamides (55.0mg,
0.25mmol), double (trifluoroacetyl epoxide) iodobenzenes (107.2mg, 0.25mmol), 4-N- morpholines-phenyl diphenylphosphine
(100.9mg, 0.75mmol), and be added sequentially in the Schlenk bottles of 25mL, add refined dimethyl sulfoxide
(3.0mL), it is placed in 120 DEG C of oil baths and reacts 30h.After reaction terminates, removal of solvent under reduced pressure is made using petrol ether/ethyl acetate
For eluant, silica gel post separation, the receipts of 4-Trifluoromethyl-N- (quinolin-2-yl) benzenesulfonamide
Rate is 67%.1H NMR (400MHz, DMSO) δ 13.42 (s, 1H), 8.32 (d, J=9.5Hz, 1H), 8.13 (d, J=8.0Hz,
2H), 7.94 (d, J=8.2Hz, 2H), 7.87 (d, J=7.8Hz, 1H), 7.74-7.71 (m, 1H), 7.63-7.59 (m, 2H),
7.44–7.41(m,1H);13C NMR(101MHz,DMSO)δ155.5,147.6,142.3,132.3,131.8,131.5,
128.4,127.0,126.2,125.0,124.5,122.3,121.2,115.5;IR(KBr)υ(cm-1)3421,3022,2956,
2923,2868,1670,1510,1466,1378,1157,1110,1021,817,756,744;HRMS(EI)Calculated
for C16H11N2O2F3S 352.0493[M+],found 352.0496.
Embodiment 5:The conjunction of N- (6-Methoxyquinolin-2-yl) -4-methylbenzenesulfonamide (1f)
Into
Accurately weigh p-methylphenyl sulphonylamine (42.8mg, 0.25mmol), 6- methoxy quinoline nitrogen oxides (44.0mg,
0.25mmol), iodobenzene acetate (320.8mg, 1.00mmol), triphenylphosphine (262.4mg, 1.00mmol), and be added sequentially to
In the Schlenk bottles of 25mL, acetonitrile (0.50mL), 20 DEG C of reaction 8h are added.After reaction terminates, removal of solvent under reduced pressure, using stone
Oily ether/ethyl acetate is used as eluant, silica gel post separation, N- (6-methoxyquinolin-2-yl) -4-
The yield of methylbenzenesulfonamide is 80%.White solid (131.3mg, 80%yield), mp 255-
257℃.1H-NMR(d6-DMSO,400MHz):7.97 (d, J=9.3Hz, 1H), 7.64 (d, J=7.4Hz, 2H), 7.46-7.43
(m, 2H), 7.38-7.36 (m, 2H), 7.13 (d, J=8.3Hz, 2H), 3.62 (s, 3H), 2.13 (s, 3H);13C-NMR(d6-
DMSO,101MHz):155.7,141.8,133.2,132.2,132.0,131.5,131.4,129.2,128.8,128.7,
126.3,122.3,107.8,55.5,20.9;IR(KBr)(cm-1)3433,2916,1608,1393,1367,1269,1089,
954,816,722,663,585,543,467;HRMS-ESI(m/z):[M]+Calculated for C17H16N2O3S,
328.0882;found,328.0866.
Claims (2)
1. a kind of preparation method of N-2- quinolyls arylsulfonamides compound, it is characterised in that:With aryl sulfonic acid amides and quinoline
Quinoline nitrogen oxides derivant is raw material, and with trivalent iodine compound as oxidant, triaryl phosphine compound is additive, organic
Reacting by heating in solvent, synthesizes a series of N-2- quinolyls arylsulfonamides compounds, and reaction equation is as follows:
In formula, the aryl sulfonic acid amides are selected from p-methylphenyl sulphonylamine, 4- chlorobenzene sulfonamides, 4- nitrobenzene sulfonamides or 4- trifluoros
One kind in methyl benzenesulfonamide;
The Quinoline N-Oxide derivant is selected from Quinoline N-Oxide, 4- methylquinolines nitrogen oxides or 6- methoxy quinoline nitrogen
One kind in oxide;
The one kind of iodonium compound oxidation agent in iodobenzene acetate or double (trifluoroacetyl epoxide) iodobenzenes;
The one kind of the triaryl phosphine compound additive in triphenylphosphine or 4-N- morpholines-phenyl diphenylphosphine;
The organic solvent is selected from ether, benzene, toluene, 1,4- dioxane, dimethyl sulfoxide, N,N-dimethylformamide, first
Alcohol, ethanol, 1,2- dichloroethanes, n-butyl alcohol, dichloromethane, chloroform, hexamethylene, n-butyl ether, carbon tetrachloride, acetic acid second
One or two mixed solvents in ester, petroleum ether, methyl tertiary butyl ether(MTBE), tetrahydrofuran, acetone or acetonitrile.
2. a kind of preparation method of N-2- quinolyls arylsulfonamides compound according to claim 1, it is characterised in that
Comprise the following steps:
A aryl sulfonic acid amides, Quinoline N-Oxide derivant, the agent of iodonium compound oxidation and triaryl phosphine compound are added by ()
Plus agent is added sequentially in the Schlenk bottles of 25mL, then adds during refined organic solvent is placed in oil bath and react, instead
Answer temperature control at 20-130 DEG C, response time control is derived with Quinoline N-Oxide in 7-30 hours, the aryl sulfonic acid amides
The mol ratio of thing is 1.0:1.0th, the mol ratio of the aryl sulfonic acid amides and iodonium compound oxidation agent is 1.0:0.5-4.0、
The aryl sulfonic acid amides are 1.0 with the mol ratio of triaryl phosphine compound additive:0.5-4.0, the organic solvent plus
It is 10-100 times of aryl sulfonic acid amides quality to enter amount;
B () reaction terminates after, organic solvent is removed under reduced pressure;
C () is obtained series N-2- quinolyl arylsulfonamides chemical combination using petrol ether/ethyl acetate eluting, Jing silica gel post separation
Thing.
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