CN104447536A - 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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- CN104447536A CN104447536A CN201410579457.2A CN201410579457A CN104447536A CN 104447536 A CN104447536 A CN 104447536A CN 201410579457 A CN201410579457 A CN 201410579457A CN 104447536 A CN104447536 A CN 104447536A
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- Prior art keywords
- sulfonic acid
- acid amides
- aryl sulfonic
- compounds
- quinolyl
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- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- GIIWGCBLYNDKBO-UHFFFAOYSA-N Quinoline 1-oxide Chemical class C1=CC=C2[N+]([O-])=CC=CC2=C1 GIIWGCBLYNDKBO-UHFFFAOYSA-N 0.000 claims abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 16
- 239000003960 organic solvent Substances 0.000 claims abstract description 12
- 239000000654 additive Substances 0.000 claims abstract description 10
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 238000010438 heat treatment Methods 0.000 claims abstract description 4
- -1 aryl sulfonic acid Chemical compound 0.000 claims description 47
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 30
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 28
- 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
- 230000000996 additive effect Effects 0.000 claims description 9
- 150000003003 phosphines Chemical class 0.000 claims description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 229910002027 silica gel Inorganic materials 0.000 claims description 8
- 239000000741 silica gel Substances 0.000 claims description 8
- 229960001866 silicon dioxide Drugs 0.000 claims description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 230000003647 oxidation Effects 0.000 claims description 6
- 238000007254 oxidation reaction Methods 0.000 claims description 6
- 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
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- TVHXQQJDMHKGGK-UHFFFAOYSA-N 4-(trifluoromethyl)benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(C(F)(F)F)C=C1 TVHXQQJDMHKGGK-UHFFFAOYSA-N 0.000 claims description 3
- HHHDJHHNEURCNV-UHFFFAOYSA-N 4-chlorobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C(Cl)C=C1 HHHDJHHNEURCNV-UHFFFAOYSA-N 0.000 claims description 3
- QWKKYJLAUWFPDB-UHFFFAOYSA-N 4-nitrobenzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=C([N+]([O-])=O)C=C1 QWKKYJLAUWFPDB-UHFFFAOYSA-N 0.000 claims description 3
- HFDLDPJYCIEXJP-UHFFFAOYSA-N 6-methoxyquinoline Chemical compound N1=CC=CC2=CC(OC)=CC=C21 HFDLDPJYCIEXJP-UHFFFAOYSA-N 0.000 claims description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 3
- PCRAJOWHMTYSKR-UHFFFAOYSA-N iodobenzene;2,2,2-trifluoroacetic acid Chemical class OC(=O)C(F)(F)F.IC1=CC=CC=C1 PCRAJOWHMTYSKR-UHFFFAOYSA-N 0.000 claims description 3
- 239000012046 mixed solvent Substances 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound 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
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-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
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 2
- 229960001701 chloroform Drugs 0.000 claims description 2
- 230000006837 decompression Effects 0.000 claims description 2
- 125000001033 ether group Chemical group 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 230000015572 biosynthetic process Effects 0.000 abstract description 11
- 238000003786 synthesis reaction Methods 0.000 abstract description 11
- 238000000034 method Methods 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract description 2
- 125000004421 aryl sulphonamide group Chemical group 0.000 abstract 1
- 238000003889 chemical engineering Methods 0.000 abstract 1
- 239000012847 fine chemical Substances 0.000 abstract 1
- 150000002497 iodine compounds Chemical class 0.000 abstract 1
- 239000007800 oxidant agent Substances 0.000 abstract 1
- 230000001590 oxidative effect Effects 0.000 abstract 1
- 238000001308 synthesis method Methods 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 238000005481 NMR spectroscopy Methods 0.000 description 12
- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 9
- 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 7
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 6
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 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 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
- GCMNJUJAKQGROZ-UHFFFAOYSA-N 1,2-Dihydroquinolin-2-imine Chemical compound C1=CC=CC2=NC(N)=CC=C21 GCMNJUJAKQGROZ-UHFFFAOYSA-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
- 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
- QKJAZPHKNWSXDF-UHFFFAOYSA-N 2-bromoquinoline Chemical compound C1=CC=CC2=NC(Br)=CC=C21 QKJAZPHKNWSXDF-UHFFFAOYSA-N 0.000 description 1
- YYROPELSRYBVMQ-UHFFFAOYSA-N Cc(cc1)ccc1S(Cl)(=O)=O Chemical compound Cc(cc1)ccc1S(Cl)(=O)=O YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
- WQQUNMCGLAUAEW-UHFFFAOYSA-N O=S(c1ccc(C(F)(F)F)cc1)(Nc1nc(cccc2)c2cc1)=O Chemical compound O=S(c1ccc(C(F)(F)F)cc1)(Nc1nc(cccc2)c2cc1)=O WQQUNMCGLAUAEW-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 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
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (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-quinolyl aryl sulfonic acid amides compounds, belong to technical field of fine.
Background technology
N-2-quinolyl aryl sulfonic acid amides compounds be a class important there is bioactive molecules, its skeleton structure frequently comes across in drug molecule, has a very wide range of applications in pharmaceutical synthesis field.About the synthesis of N-2-quinolyl aryl sulfonic acid amides compounds, usually adopt the following two kinds method:
(1) aryl sulfonic acid amides and 2-Bromoquinoline linked reaction
The substrate of the method is expensive, and need previously prepared, environment is unfriendly, and Atom economy is low.[see: Baffoe, Jonathan et al.Org.Lett.2010,12,1532.].
(2) SULPHURYL CHLORIDE and 2-quinolylamine linked reaction
The substrate of the method is expensive, and need previously prepared, environment is unfriendly, and Atom economy is low.[see (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.].
Summary of the invention
In order to overcome the deficiencies in the prior art, the object of the invention is to provide a kind of preparation method of N-2-quinolyl aryl sulfonic acid amides compounds.The method has that method steps is simple, raw material is easy to get, Atom economy is high, advantages of environment protection.Because N-2-quinolyl aryl sulfonic acid amides is the important skeleton structure of a class, have a very wide range of applications in pharmaceutical synthesis field.
In order to realize foregoing invention object, solve problem existing in prior art, the technical scheme that the present invention takes is: a kind of preparation method of N-2-quinolyl aryl sulfonic acid amides compounds, for raw material with aryl sulfonic acid amides and Quinoline N-Oxide derivative, with iodonium compound for oxygenant, triaryl phosphine compounds is additive, in organic solvent reacting by heating, synthesize a series of N-2-quinolyl aryl sulfonic acid amides compounds, reaction formula is as follows:
In formula, described aryl sulfonic acid amides is selected from the one in p-methylphenyl sulphonylamine, 4-chlorobenzene sulfonamide, 4-nitrobenzene sulfonamide or 4-trifluoromethyl benzene sulfonamide;
Described Quinoline N-Oxide derivative is selected from the one in Quinoline N-Oxide, 4-toluquinoline oxynitride or 6-methoxy quinoline oxynitride;
The agent of described iodonium compound oxidation is selected from the one in acetic acid iodobenzene, two trifluoroacetic acid iodobenzenes or two trifluoro ethoxy iodobenzenes;
Described triaryl phosphine compounds additive is selected from the one in triphenylphosphine or 4-N-morpholine-phenyl diphenylphosphine;
Described organic solvent is selected from ether, benzene, toluene, 1,4-dioxane, dimethyl sulfoxide (DMSO), N, one or both mixed solvents in dinethylformamide, methyl alcohol, ethanol, 1,2-ethylene dichloride, propyl carbinol, methylene dichloride, trichloromethane, hexanaphthene, n-butyl ether, tetracol phenixin, ethyl acetate, sherwood oil, methyl tertiary butyl ether, tetrahydrofuran (THF), acetone or acetonitrile.
The preparation method of described a kind of N-2-quinolyl aryl sulfonic acid amides compounds, comprises the following steps:
A () is by aryl sulfonic acid amides, Quinoline N-Oxide derivative, the agent of iodonium compound oxidation and triaryl phosphine compounds additive join in the Schlenk bottle of 25mL successively, and then add refined organic solvent and be placed in oil bath and react, temperature of reaction controls at 20-130 DEG C, reaction times controls at 7-30 hour, the mol ratio of described aryl sulfonic acid amides and Quinoline N-Oxide derivative is 1.0:1.0, the mol ratio of described aryl sulfonic acid amides and the agent of iodonium compound oxidation is 1.0:0.5-4.0, the mol ratio of described aryl sulfonic acid amides and triaryl phosphine compounds additive is 1.0:0.5-4.0, the add-on of described organic solvent is 10-100 times of aryl sulfonic acid amides quality,
B () reaction terminates after, decompression removing organic solvent;
C () uses petrol ether/ethyl acetate wash-out, be separated obtained serial N-2-quinolyl aryl sulfonic acid amides compounds through silicagel column.
Beneficial effect of the present invention is: a kind of preparation method of N-2-quinolyl aryl sulfonic acid amides compounds, for raw material with aryl sulfonic acid amides and Quinoline N-Oxide derivative, with iodonium compound for oxygenant, triaryl phosphine compounds is additive, reacting by heating in organic solvent, synthesizes a series of N-2-quinolyl aryl sulfonic acid amides compounds.Compared with the prior art, the present invention mainly provides a kind of synthetic method of simple efficient, Atom economy high, eco-friendly N-2-quinolyl arylsulfonamide compounds, and the method has that method steps is simple, raw material is easy to get, Atom economy is high, advantages of environment protection.Because N-2-quinolyl aryl sulfonic acid amides is the important skeleton structure of a class, has a very wide range of applications in pharmaceutical synthesis field, there are larger use value and economic results in society.
Accompanying drawing explanation
Fig. 1 is compound 1a's
1h-NMR.
Fig. 2 is compound 1a's
13c-NMR.
Fig. 3 is compound 1b's
1h-NMR.
Fig. 4 is compound 1b's
13c-NMR.
Fig. 5 is compound 1c's
1h-NMR.
Fig. 6 is compound 1c's
13c-NMR.
Fig. 7 is compound 1d's
1h-NMR.
Fig. 8 is compound 1d's
13c-NMR.
Fig. 9 is compound 1e's
1h-NMR.
Figure 10 is compound 1e's
13c-NMR.
Figure 11 is compound 1f's
1h-NMR.
Figure 12 is compound 1f's
13c-NMR.
Embodiment
Below in conjunction with embodiment, the invention will be further described:
The synthesis of embodiment 1:4-Methyl-N-(quinolin-2-yl) benzenesulfonamide (1a)
Accurately take p-methylphenyl sulphonylamine (42.8mg, 0.25mmol), Quinoline N-Oxide (36.3mg, 0.25mmol), acetic acid iodobenzene (40.1mg, 0.125mmol), triphenylphosphine (32.8mg, 0.125mmol), and join successively in the Schlenk bottle of 25mL, add refined acetonitrile (0.50mL), 20 DEG C of reaction 8h.After reaction terminates, removal of solvent under reduced pressure, use petrol ether/ethyl acetate as eluent, silicagel column is separated, and the yield of 4-Methyl-N-(quinolin-2-yl) benzenesulfonamide is 80%.
1H NMR(400MHz,CDCl
3)δ11.86(s,1H),7.88(dd,J＝13.6,8.8Hz,1H),7.61(t,J＝6.5Hz,1H),7.46(d,J＝8.5Hz,1H),7.35(t,J＝7.5Hz,1H),7.26(d,J＝5.8Hz,1H),6.95(d,J＝9.4Hz,1H),2.39(s,1H)；
13C NMR(101MHz,CDCl
3)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 C
16H
14N
2O
2S,299.0854；found,299.0866.
The synthesis of embodiment 2:4-Chloro-N-(quinolin-2-yl) benzenesulfonamide (1b)
Accurately take 4-chlorobenzene sulfonamide (42.8mg, 0.25mmol), Quinoline N-Oxide (36.3mg, 0.25 mmol), two trifluoro ethoxy iodobenzene (107.0mg, 0.5mmol), 4-N-morpholine-phenyl diphenylphosphine (47.6mg, 0.25mmol), and join successively in the Schlenk bottle of 25mL, add refined hexanaphthene (3.0mL), be placed in 100 DEG C of oil baths and react 10h.After reaction terminates, removal of solvent under reduced pressure, use petrol ether/ethyl acetate as eluent, silicagel column is separated, and the yield of 4-Chloro-N-(quinolin-2-yl) benzenesulfonamide is 63%.
1H NMR(400MHz,DMSO)δ13.38(s,1H),8.28(d,J＝9.5Hz,1H),7.90(d,J＝8.4Hz,2H),7.87–7.82(m,1H),7.73–7.67(m,1H),7.67–7.57(m,3H),7.54(d,J＝9.3Hz,1H),7.43–7.37(m,1H)；
13C NMR(101MHz,DMSO)δ155.6,142.8,142.2,136.7,132.4,130.6,129.3,128.5,128.2,124.6,121.3,117.3,115.7；IR(KBr)υ(cm
-1)3444,3321,2956,2917,2848,1659,1604,1509,1478,1380,1224,1157,1093,1015,909,830,816,777,758,734；HRMS(EI)Calculated for C
15H
11N
2O
2SCl 318.0230[M+],found 318.0235.
The synthesis of embodiment 3:4-Nitro-N-(quinolin-2-yl) benzenesulfonamide (1c)
Accurately take 4-nitrobenzene sulfonamide (50.5mg, 0.25mmol), Quinoline N-Oxide (44.3mg, 0.25mmol), acetic acid iodobenzene (123.5mg, 0.5mmol), triphenylphosphine (17.9mg, 0.125mmol), and join successively in the Schlenk bottle of 25mL, add refined toluene (3.0mL), be placed in 60 DEG C of oil baths and react 7h.After reaction terminates, removal of solvent under reduced pressure, use petrol ether/ethyl acetate as eluent, silicagel column is separated, and the yield of 4-Nitro-N-(quinolin-2-yl) benzenesulfonamide is 76%.
1H NMR(400MHz,DMSO)δ13.43(s,1H),8.17(d,J＝8.3Hz,2H),7.87(d,J＝7.9Hz,1H),7.76–7.69(m,1H),7.69–7.59(m,4H),7.57(d,J＝5.8Hz,1H),7.42(t,J＝7.3Hz,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 C
15H
11N
3O
4S 329.0470[M+],found 329.0478.
The synthesis of embodiment 4:4-Methyl-N-(quinolin-2-yl) benzenesulfonamide (1d)
Accurately take p-methylphenyl sulphonylamine (42.8mg, 0.25mmol), 4-toluquinoline oxynitride (50.5mg, 0.25mmol), acetic acid iodobenzene (40.1mg, 0.125mmol), triphenylphosphine (32.8mg, 0.125mmol), and join successively in the Schlenk bottle of 25mL, add acetonitrile (2.50mL) and toluene (2.50mL) mixed solvent, 20 DEG C of reaction 8h.After reaction terminates, removal of solvent under reduced pressure, use petrol ether/ethyl acetate as eluent, silicagel column is separated, and the yield of 4-Methyl-N-(quinolin-2-yl) benzenesulfonamide is 80%.White solid(62.4mg,40％yield),mp 225-227℃.
1H-NMR(d
6-DMSO,400MHz):12.90(bs,1H),7.87(d,J＝7.96Hz,1H),7.81(d,J＝7.48Hz,2H),7.69-7.65(m,1H),7.57(d,J＝8.08Hz,1H),7.42(s,1H),7.39-7.33(m,3H),2.57(s,3H),2.35(s,3H)；
13C-NMR(d
6-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 C
17H
16N
2O
2S,312.0932；found,312.0930.
The synthesis of embodiment 5:4-Trifluoromethyl-N-(quinolin-2-yl) benzenesulfonamide (1e)
Accurately take Quinoline N-Oxide (44.3mg, 0.25mmol), 4-trifluoromethyl benzene sulfonamide (55.0mg, 0.25mmol), two trifluoroacetic acid iodobenzene (103.2mg, 0.5mmol), 4-N-morpholine-phenyl diphenylphosphine (100.9mg, 0.75mmol), and join successively in the Schlenk bottle of 25mL, add refined dimethyl sulfoxide (DMSO) (3.0mL), be placed in 120 DEG C of oil baths and react 30h.After reaction terminates, removal of solvent under reduced pressure, use petrol ether/ethyl acetate as eluent, silicagel column is separated, and the yield of 4-Trifluoromethyl-N-(quinolin-2-yl) benzenesulfonamide is 67%.
1H NMR(400MHz,DMSO)δ13.42(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),7.73(t,J＝7.4Hz,1H),7.67–7.52(m,2H),7.43(t,J＝7.4Hz,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 C
16H
11N
2O
2F
3S352.0493[M+],found 352.0496.
The synthesis of embodiment 6:N-(6-Methoxyquinolin-2-yl)-4-methylbenzenesulfonamide (1f)
Accurately take p-methylphenyl sulphonylamine (42.8mg, 0.25mmol), 6-methoxy quinoline oxynitride (44.0mg, 0.25mmol), acetic acid iodobenzene (320.8mg, 1.00mmol), triphenylphosphine (262.4mg, 1.00mmol), and join successively in the Schlenk bottle of 25mL, add acetonitrile (0.50mL), 20 DEG C of reaction 8h.After reaction terminates, removal of solvent under reduced pressure, use petrol ether/ethyl acetate as eluent, silicagel column is separated, and the yield of N-(6-methoxyquinolin-2-yl)-4-methylbenzenesulfonamide is 80%.White solid(131.3mg,80％yield),mp 255-257℃.
1H-NMR(d
6-DMSO,400MHz):7.97(d,J＝9.32Hz,1H),7.64(d,J＝7.44Hz,2H),7.46-7.43(m,2H),7.74(d,J＝5.16Hz,2H),7.13(d,J＝8.28Hz,2H),3.62(s,3H),2.21(s,3H)；
13C-NMR(d
6-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 C
17H
16N
2O
3S,328.0882；found,328.0866。
Claims (2)
1. the preparation method of a N-2-quinolyl aryl sulfonic acid amides compounds, it is characterized in that: with aryl sulfonic acid amides and Quinoline N-Oxide derivative for raw material, with iodonium compound for oxygenant, triaryl phosphine compounds is additive, reacting by heating in organic solvent, synthesize a series of N-2-quinolyl aryl sulfonic acid amides compounds, reaction formula is as follows:
In formula, described aryl sulfonic acid amides is selected from the one in p-methylphenyl sulphonylamine, 4-chlorobenzene sulfonamide, 4-nitrobenzene sulfonamide or 4-trifluoromethyl benzene sulfonamide;
Described Quinoline N-Oxide derivative is selected from the one in Quinoline N-Oxide, 4-toluquinoline oxynitride or 6-methoxy quinoline oxynitride;
The agent of described iodonium compound oxidation is selected from the one in acetic acid iodobenzene, two trifluoroacetic acid iodobenzenes or two trifluoro ethoxy iodobenzenes;
Described triaryl phosphine compounds additive is selected from the one in triphenylphosphine or 4-N-morpholine-phenyl diphenylphosphine;
Described organic solvent is selected from ether, benzene, toluene, 1,4-dioxane, dimethyl sulfoxide (DMSO), N, one or both mixed solvents in dinethylformamide, methyl alcohol, ethanol, 1,2-ethylene dichloride, propyl carbinol, methylene dichloride, trichloromethane, hexanaphthene, n-butyl ether, tetracol phenixin, ethyl acetate, sherwood oil, methyl tertiary butyl ether, tetrahydrofuran (THF), acetone or acetonitrile.
2. the preparation method of a kind of N-2-quinolyl aryl sulfonic acid amides compounds according to claim 1, is characterized in that comprising the following steps:
A () is by aryl sulfonic acid amides, Quinoline N-Oxide derivative, the agent of iodonium compound oxidation and triaryl phosphine compounds additive join in the Schlenk bottle of 25 mL successively, and then add refined organic solvent and be placed in oil bath and react, temperature of reaction controls at 20-130 DEG C, reaction times controls at 7-30 hour, the mol ratio of described aryl sulfonic acid amides and Quinoline N-Oxide derivative is 1.0:1.0, the mol ratio of described aryl sulfonic acid amides and the agent of iodonium compound oxidation is 1.0:0.5-4.0, the mol ratio of described aryl sulfonic acid amides and triaryl phosphine compounds additive is 1.0:0.5-4.0, the add-on of described organic solvent is 10-100 times of aryl sulfonic acid amides quality,
B () reaction terminates after, decompression removing organic solvent;
C () uses petrol ether/ethyl acetate wash-out, be separated obtained serial N-2-quinolyl aryl sulfonic acid amides compounds through silicagel column.
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| CN108329262A (en) * | 2018-02-07 | 2018-07-27 | 温州大学 | The synthetic method of N- (2- quinolyls) benzamide compound |
| CN108373448A (en) * | 2018-04-23 | 2018-08-07 | 中南大学 | A kind of microwave assisted synthesizing method of N- (quinoline -2- bases) aromatic amides |
| CN108409652A (en) * | 2018-04-13 | 2018-08-17 | 中南大学 | A kind of preparation method of ultrasonic wave added N- (quinoline -2- bases) alkylamide |
| CN108610304A (en) * | 2018-06-19 | 2018-10-02 | 陕西师范大学 | A kind of two fragrant and sultam class compound synthetic methods |
| CN109485598A (en) * | 2018-11-29 | 2019-03-19 | 河南师范大学 | The new method of quinoline protecting group on a kind of removal amino |
| CN112724083A (en) * | 2021-01-06 | 2021-04-30 | 常州工学院 | Method for synthesizing secondary sulfonamide compound from benzamide compound and direct ortho-amine and application |
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| CN112724083A (en) * | 2021-01-06 | 2021-04-30 | 常州工学院 | Method for synthesizing secondary sulfonamide compound from benzamide compound and direct ortho-amine and application |
| CN112724083B (en) * | 2021-01-06 | 2022-09-02 | 常州工学院 | Method for synthesizing secondary sulfonamide compound from benzamide compound and direct ortho-amine and application |
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