CN110204504A - The more two thiocarbohydrazone derivatives of piperazines of triazine radical and its synthetic method and application - Google Patents
The more two thiocarbohydrazone derivatives of piperazines of triazine radical and its synthetic method and application Download PDFInfo
- Publication number
- CN110204504A CN110204504A CN201910315324.7A CN201910315324A CN110204504A CN 110204504 A CN110204504 A CN 110204504A CN 201910315324 A CN201910315324 A CN 201910315324A CN 110204504 A CN110204504 A CN 110204504A
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- CN
- China
- Prior art keywords
- thiocarbohydrazone
- piperazines
- derivatives
- compound
- triazine radical
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 150000004885 piperazines Chemical class 0.000 title claims abstract description 32
- 238000010189 synthetic method Methods 0.000 title claims description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000006467 substitution reaction Methods 0.000 claims abstract description 13
- 230000007062 hydrolysis Effects 0.000 claims abstract description 8
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 8
- 150000002500 ions Chemical group 0.000 claims abstract description 5
- XTEGARKTQYYJKE-UHFFFAOYSA-N chloric acid Chemical compound OCl(=O)=O XTEGARKTQYYJKE-UHFFFAOYSA-N 0.000 claims abstract description 4
- 229940005991 chloric acid Drugs 0.000 claims abstract description 4
- 125000001424 substituent group Chemical group 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 24
- 239000002585 base Substances 0.000 claims description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 20
- 239000003960 organic solvent Substances 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 15
- 239000003513 alkali Substances 0.000 claims description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 claims description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 235000019441 ethanol Nutrition 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 229910001385 heavy metal Inorganic materials 0.000 claims description 4
- 230000003287 optical effect Effects 0.000 claims description 4
- 239000000523 sample Substances 0.000 claims description 4
- 239000012855 volatile organic compound Substances 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 3
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- 229910052738 indium Inorganic materials 0.000 claims 1
- 229910052744 lithium Inorganic materials 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 40
- 239000000126 substance Substances 0.000 abstract description 10
- 230000000694 effects Effects 0.000 abstract description 6
- 238000000034 method Methods 0.000 abstract description 4
- 125000004193 piperazinyl group Chemical class 0.000 abstract description 4
- 210000000080 chela (arthropods) Anatomy 0.000 abstract description 3
- 229910001428 transition metal ion Inorganic materials 0.000 abstract description 3
- 125000006841 cyclic skeleton Chemical group 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 description 38
- 230000015572 biosynthetic process Effects 0.000 description 36
- 238000005481 NMR spectroscopy Methods 0.000 description 35
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 26
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 17
- 238000010792 warming Methods 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 238000012805 post-processing Methods 0.000 description 12
- 239000000376 reactant Substances 0.000 description 12
- 239000002253 acid Substances 0.000 description 10
- 229940125898 compound 5 Drugs 0.000 description 10
- 238000000746 purification Methods 0.000 description 10
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 9
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 9
- HTSVYUUXJSMGQC-UHFFFAOYSA-N 2-chloro-1,3,5-triazine Chemical compound ClC1=NC=NC=N1 HTSVYUUXJSMGQC-UHFFFAOYSA-N 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- -1 1- pyridyl group Chemical group 0.000 description 7
- QKOFSFOOALTCPW-UHFFFAOYSA-N 2-piperazin-1-yl-1,3,5-triazine Chemical compound C1CNCCN1C1=NC=NC=N1 QKOFSFOOALTCPW-UHFFFAOYSA-N 0.000 description 7
- 229940126214 compound 3 Drugs 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 description 6
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 6
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 6
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 6
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 6
- 229940125797 compound 12 Drugs 0.000 description 6
- 229940125758 compound 15 Drugs 0.000 description 6
- 239000001257 hydrogen Substances 0.000 description 6
- 229910052739 hydrogen Inorganic materials 0.000 description 6
- 239000001103 potassium chloride Substances 0.000 description 6
- 235000011164 potassium chloride Nutrition 0.000 description 6
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 5
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 5
- 229940126657 Compound 17 Drugs 0.000 description 5
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 description 5
- 229940125773 compound 10 Drugs 0.000 description 5
- 229940126543 compound 14 Drugs 0.000 description 5
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 235000011181 potassium carbonates Nutrition 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 3
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- 229940126142 compound 16 Drugs 0.000 description 3
- 238000006073 displacement reaction Methods 0.000 description 3
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 230000000269 nucleophilic effect Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 2
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 2
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 235000015320 potassium carbonate Nutrition 0.000 description 2
- 238000001338 self-assembly Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 125000006414 CCl Chemical group ClC* 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 229940043237 diethanolamine Drugs 0.000 description 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000005909 ethyl alcohol group Chemical group 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- DYUWTXWIYMHBQS-UHFFFAOYSA-N n-prop-2-enylprop-2-en-1-amine Chemical compound C=CCNCC=C DYUWTXWIYMHBQS-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229920001596 poly (chlorostyrenes) Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 150000003921 pyrrolotriazines Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 1
- IPISOFJLWYBCAV-UHFFFAOYSA-N tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole-1-carboxylate Chemical compound C1=NN(C(=O)OC(C)(C)C)C=C1B1OC(C)(C)C(C)(C)O1 IPISOFJLWYBCAV-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/12—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D251/26—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with only hetero atoms directly attached to ring carbon atoms
- C07D251/40—Nitrogen atoms
- C07D251/54—Three nitrogen atoms
- C07D251/70—Other substituted melamines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K11/00—Luminescent, e.g. electroluminescent, chemiluminescent materials
- C09K11/06—Luminescent, e.g. electroluminescent, chemiluminescent materials containing organic luminescent materials
-
- C—CHEMISTRY; METALLURGY
- C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
- C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
- C09K2211/00—Chemical nature of organic luminescent or tenebrescent compounds
- C09K2211/10—Non-macromolecular compounds
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Abstract
The invention discloses a kind of more two thiocarbohydrazone derivatives of piperazines of triazine radical, the more two thiocarbohydrazone derivatives of piperazines of the triazine radical synthesize with the following method: (1) 1- piperazine-Boc, Cyanuric Chloride ,-R1With-R2Substitution reaction occurs for substituent group, generates intermediate c；(2) hydrolysis occurs for the intermediate c and hydrochloric acid, takes off-Boc base, obtains intermediate d；(3) the intermediate d and CS2Thiocarboxylic's reaction occurs, obtains finished product.The more two thiocarbohydrazone derivatives of piperazines of triazine radical provided in the present invention can improve the chemical stability of corresponding thiocarbohydrazone compound by the semi-rigid six-membered cyclic skeleton of piperazine group by push-pull electronic effect, its with unique pincer structure, can and transition metal ions form that coordination is strong, super molecular complex of stable in physicochemical property.The present invention also provides the applications of the more two thiocarbohydrazone derivatives of piperazines of triazine radical.
Description
Technical field
The invention belongs to technical field of organic synthesis, are related to a kind of multiple tooth metal organic complex donor, more specifically,
It is related to a kind of more two thiocarbohydrazone derivatives of piperazines of triazine radical and its synthetic method and application.
Background technique
Thiocarbohydrazone derivative bioprobe, coordination catalysis, Supramolecular self assembly and in terms of
It has a wide range of applications.The thiocarbohydrazone derivative controllable method for preparing of different function has been realized by chemical synthesis process
It is concerned by people.
From the point of view of current document report, fatty two thiocarbohydrazone derivative of amido is closed by reaction in-situ " one kettle way "
At what is obtained, but obtained compound separation difficult to realize and characterization, and the property of product is extremely unstable, easily and in air
Oxygen reacts to form persulfide, is difficult to store at room temperature, and then influences the Coordinate self-assembly and sulphur-alkene with metal ion
With sulphur-alkynes polymer reaction activity.
In view of the extensive use of thiocarbohydrazone derivative, it is necessary to provide a kind of chemical property more stable thio kappa
Hydazone derivative.
Summary of the invention
It is an object of the invention to overcome above-mentioned technical deficiency, propose that a kind of more two thiocarbohydrazones of piperazines of triazine radical spread out
Biology, the thiocarbohydrazone derivatives chemical property are stablized, and it is with unique pincer structure, can be with transition metal ions shape
Strong, stable in physicochemical property the super molecular complex at coordination；The purpose of second aspect of the present invention is, provides a kind of triazine
The synthetic method of two thiocarbohydrazone derivative of Quito piperazines；The purpose of third aspect present invention is, provides a kind of triazine
The application of two thiocarbohydrazone derivative of Quito piperazines.
To reach above-mentioned technical purpose, technical solution of the present invention provides a kind of more two thiocarbohydrazones of piperazines of triazine radical
Derivative has the following structure formula:
Wherein, R1And R2Independently of each other, R1And R2Be respectively selected from A1, A2, A3, A4 or
A5:
Technical solution of the present invention also provides a kind of synthetic method of more two thiocarbohydrazone derivatives of piperazines of triazine radical,
Include the following steps:
S1,1- piperazine-Boc, Cyanuric Chloride ,-R1With-R2Substitution reaction occurs for substituent group, generates intermediate c；
Hydrolysis occurs for S2, the intermediate c and hydrochloric acid, takes off-Boc base, obtains intermediate d；
S3, the intermediate d and CS2Thiocarboxylic's reaction occurs, obtains finished product.
Technical solution of the present invention additionally provides a kind of more two thiocarbohydrazone derivatives of piperazines of triazine radical in heavy metal
Application in terms of ion fluorescence probe, OLED luminescent material, VOCs fluorescent optical sensor, supermolecule photoswitch.
Compared with prior art, the beneficial effect comprise that
1, the more two thiocarbohydrazone derivatives of piperazines of triazine radical provided in the present invention pass through the semi-rigid of piperazine group
Six-membered cyclic skeleton can improve the chemical stability of corresponding thiocarbohydrazone compound by push-pull electronic effect, have
Unique pincer structure, can and transition metal ions form that coordination is strong, super molecular complex of stable in physicochemical property；
2, synthetic method provided by the invention as starting material and makes full use of 1,3,5- in Cyanuric Chloride using Cyanuric Chloride
The activity difference of the nucleophilic displacement of fluorine of the C-Cl key of position, reacts to obtain property by substitution reaction, hydrolysis and thiocarboxylic
The more two thiocarbohydrazone derivatives of piperazines of stable triazine radical, to realize that the more piperazinyl rigid backbone molecular fractionations of classification are controllable
Function dough；And of the invention synthetic method is simple, yield is high, storage ability is good at room temperature for the product of synthesis；
3, the more two thiocarbohydrazone derivatives of piperazines of triazine radical provided by the invention can be applied to heavy metal ion fluorescence
Probe, OLED luminescent material, VOCs fluorescent optical sensor and supermolecule photoswitch etc. are also used as Jin-gold bonding effect
The synthesis material of the organic polymer self-assembled material of driving has further widened more two thiocarbohydrazones of piperazines of triazine radical and has spread out
The application of biology.
Detailed description of the invention
Fig. 1 is the nuclear magnetic resonance spectroscopy spectrogram of compound 3 obtained in the embodiment of the present invention 1；
Fig. 2 is the carbon-13 nmr spectra spectrogram of compound 3 obtained in the embodiment of the present invention 1；
Fig. 3 is the nuclear magnetic resonance spectroscopy spectrogram of compound 5 obtained in the embodiment of the present invention 1；
Fig. 4 is the carbon-13 nmr spectra spectrogram of compound 5 obtained in the embodiment of the present invention 1；
Fig. 5 is the nuclear magnetic resonance spectroscopy spectrogram of compound 6 obtained in the embodiment of the present invention 2；
Fig. 6 is the carbon-13 nmr spectra spectrogram of compound 6 obtained in the embodiment of the present invention 2；
Fig. 7 is the mass spectrogram of compound 6 obtained in the embodiment of the present invention 2；
Fig. 8 is the carbon-13 nmr spectra spectrogram of compound 7 obtained in the embodiment of the present invention 2；
Fig. 9 is the nuclear magnetic resonance spectroscopy spectrogram of compound 8 obtained in the embodiment of the present invention 2；
Figure 10 is the carbon-13 nmr spectra spectrogram of compound 8 obtained in the embodiment of the present invention 2；
Figure 11 is the mass spectrogram of compound 8 obtained in the embodiment of the present invention 2；
Figure 12 is the nuclear magnetic resonance spectroscopy spectrogram of compound 9 obtained in the embodiment of the present invention 2；
Figure 13 is the nuclear magnetic resonance spectroscopy spectrogram of compound 10 obtained in the embodiment of the present invention 3；
Figure 14 is the nuclear magnetic resonance spectroscopy spectrogram of compound 12 obtained in the embodiment of the present invention 3；
Figure 15 is the carbon-13 nmr spectra spectrogram of compound 12 obtained in the embodiment of the present invention 3；
Figure 16 is the nuclear magnetic resonance spectroscopy spectrogram of compound 13 obtained in the embodiment of the present invention 4；
Figure 17 is the carbon-13 nmr spectra spectrogram of compound 13 obtained in the embodiment of the present invention 4；
Figure 18 is the nuclear magnetic resonance spectroscopy spectrogram of compound 14 obtained in the embodiment of the present invention 4；
Figure 19 is the nuclear magnetic resonance spectroscopy spectrogram of compound 15 obtained in the embodiment of the present invention 4；
Figure 20 is the carbon-13 nmr spectra spectrogram of compound 15 obtained in the embodiment of the present invention 4；
Figure 21 is the nuclear magnetic resonance spectroscopy spectrogram of compound 17 obtained in the embodiment of the present invention 5；
Figure 22 is the nuclear magnetic resonance spectroscopy spectrogram of compound 18 obtained in the embodiment of the present invention 5；
Figure 23 is the nuclear magnetic resonance spectroscopy spectrogram of compound 19 obtained in the embodiment of the present invention 5；
Figure 24 is the carbon-13 nmr spectra spectrogram of compound 19 obtained in the embodiment of the present invention 5；
Figure 25 is the mass spectrogram of compound 19 obtained in the embodiment of the present invention 5.
Specific embodiment
In order to make the objectives, technical solutions, and advantages of the present invention clearer, with reference to the accompanying drawings and embodiments, right
The present invention is further elaborated.It should be appreciated that embodiment described herein is only used to explain the present invention, and do not have to
It is of the invention in limiting.
The embodiment provides a kind of more two thiocarbohydrazone derivatives of piperazines of triazine radical, have following knot
Structure formula:
Wherein, R1And R2Independently of each other, R1And R2It is respectively selected from A1, A2, A3, A4 or A5:
In some preferred embodiments of the invention, R1And R2It is A1；More two thiocarbohydrazones of piperazines of the triazine radical
Derivant structure is symmetrical, and property is more stable.
The embodiment of the present invention also provides a kind of synthetic method of more two thiocarbohydrazone derivatives of piperazines of triazine radical, packet
Include following steps:
(1) 1- piperazine-Boc, Cyanuric Chloride ,-R1With-R2Substitution reaction occurs for substituent group, generates intermediate c；
(2) hydrolysis occurs for intermediate c and hydrochloric acid, takes off-Boc base, obtains intermediate d；
(3) intermediate d and CS2Thiocarboxylic's reaction occurs, obtains finished product.
Substitution reaction generation intermediate c occurs in the present invention, in step (1) and is specifically divided into the following two kinds situation: if (1) R1
And R2It is A1, then three in Cyanuric Chloride-Cl is replaced by-Boc, then 1- piperazine-Boc and Cyanuric Chloride occur to replace anti-
Intermediate 3 (i.e. intermediate c), directly progress next step reaction should be directly obtained；(2) if R1 and R2 are not all A1, three polychlorostyrene
The part-Cl in cyanogen is replaced by-Boc, then 1- piperazine-Boc first occur with Cyanuric Chloride the obtained intermediate 6 of substitution reaction or
16, intermediate 6 or 16 is further continued for and-R1With-R2Nucleophilic substitution occurs, generates intermediate c.
In the present invention, in step (1), the first alkali and the first organic solvent are also added into during substitution reaction, wherein the
One alkali is one of sodium carbonate, potassium carbonate, triethylamine, DMAP, sodium bicarbonate, saleratus or a variety of；Preferably, the first alkali
For potassium carbonate.
In some preferred embodiments of the invention, the molar ratio of the first alkali and Cyanuric Chloride is 1~10:1.
In the present invention, the first organic solvent be one of tetrahydrofuran, methanol, ethyl alcohol, dioxane, methylene chloride or
It is a variety of.
In some preferred embodiments of the invention, if R1And R2It is A1, the first organic solvent is tetrahydrofuran；If
R1And R2It is not all A1, the first organic solvent is tetrahydrofuran and dioxane, wherein 1- piperazine-Boc and Cyanuric Chloride occur
Reacting the first organic solvent used in obtained intermediate 1 is tetrahydrofuran, intermediate 1 and-R1With-R2Substitution reaction institute occurs
First organic solvent is dioxane.
In the present invention, the temperature of substitution reaction is -5~150 DEG C in step (1).
In some preferred embodiments of the invention, in step (1), if R1And R2It is A1, then the temperature of substitution reaction
It is 70~100 DEG C；If R1And R2It is not all A1, then 1- piperazine-Boc prepares the anti-of intermediate 1 with Cyanuric Chloride generation substitution reaction
Answering temperature is -5~30 DEG C；Intermediate 1 and-R1With-R2Occur nucleophilic substitution prepare intermediate c reaction temperature be 110~
150℃。
The present invention makes full use of the activity difference of the nucleophilic displacement of fluorine of 1,3,5- C-Cl keys in Cyanuric Chloride, passes through control
Reaction temperature realizes Cyanuric Chloride and 1-Boc- piperazine or substep nucleophilic displacement of fluorine occurs for other nitrogenous compounds, and synthesis obtains a system
The pyrrolotriazine derivatives that more piperazines of the N-Boc protection of column replace, and then realize and be classified controllable function dough, target product yield height
And property is stablized.
In the present invention, in step (2), be also added into the second organic solvent in hydrolysis, the second organic solvent be methanol,
One of ethyl alcohol, normal propyl alcohol, isopropanol are a variety of；Preferably, the second organic solvent is ethyl alcohol.
In some preferred embodiments of the invention, the molar ratio of hydrochloric acid and intermediate c are 1~4:1 in step (2).
In the present invention, in step (2), temperature 50 C~90 DEG C of hydrolysis, the reaction time is 8~48h；Preferably,
Hydrolysising reacting temperature is 50 DEG C.
In the present invention, it is also added into the second alkali and third organic solvent in thiocarboxylic's reaction process in step (3), the
Two alkali are one of sodium hydroxide, potassium hydroxide, lithium hydroxide or a variety of；Preferably, the second alkali is potassium hydroxide.Third has
Solvent is one of methanol, ethyl alcohol, normal propyl alcohol, isopropanol or a variety of；Preferably, third organic solvent is methanol or second
Alcohol.
In some preferred embodiments of the invention, the molar ratio of the second alkali and intermediate d are 2~10:1.
In the present invention, step (3) specifically prepares finished product with the following method: intermediate d, the second alkali and third is organic molten
After agent dissolution, after mixed liquor is heated to 8~12h of reaction temperature reaction, CS is added2The reaction was continued, and 8~48h obtains finished product.
In the present invention, in step (3), the reaction temperature of thiocarboxylic's reaction is 20~60 DEG C；Preferably, reaction temperature
It is 40 DEG C.
In the present invention, CS2Molar ratio with intermediate d is 3~10:1.
The embodiments of the present invention also provide a kind of more two thiocarbohydrazone derivatives of piperazines of triazine radical heavy metal from
Application in terms of sub- fluorescence probe, OLED luminescent material, VOCs fluorescent optical sensor and supermolecule photoswitch.
Below in conjunction with specific embodiment, the present invention will be described in further detail.It should be appreciated that tool described herein
Body embodiment is only used to explain the present invention, is not intended to limit the present invention.Experimental method in the present invention, such as without special theory
It is bright, it is conventional method.Experimental material used in the present invention is that market is commercially available unless otherwise specified.
Embodiment 1:
The synthesis of 4- tri- (1- carbodithioic acid base) piperazinyl -1,3,5- triazine sylvite (compound 5):
(1) synthesis of (1-Boc yl) piperazinyl -1,3,5- triazine of 4- tri- (compound 3):
By Cyanuric Chloride (0.92g, 5.03mmol), 1- piperazine-Boc (3.3g, 5.21mmol), K2CO3 (0.69g,
It 5mmol) is added in 80mL tetrahydrofuran organic solvent, is stirred continuously, mixed liquor is warming up to 85 DEG C of reflux, in nitrogen protection
It after lower reaction 48h, is spin-dried for, washes, filters, dries by vacuum, obtain dry compound 3 (2.83g, yield 89%)；
(2) synthesis of three piperazinyl -1,3,5- triazine (compound 4) of 4- (1- hydrogen):
5mL water and 5mL concentrated hydrochloric acid is added using 20mL ethyl alcohol as solvent in Weigh Compound 3 (2.80g, 4.42mmol)
(1M), is stirred continuously, and is warming up to 50 DEG C of reflux, reacts 48h under nitrogen protection；After the reaction was completed, solvent is spin-dried for, is added
Water is added dropwise NaOH concentrated solution to pH of mixed and reaches 14 after ultrasonic, 50mL methylene chloride is added and is stirred continuously and extracts, will
Organic phase after liquid separation is spare, and water phase is carried out liquid separation again using 50mL methylene chloride, is repeated above extracting operation 3~5 times,
By all liquid separations obtain it is organic mix after, it is dry using 4g anhydrous sodium sulfate and depressurize and be spin-dried for solvent to get to compound 4
(1.25g, yield 85%)；
(3) synthesis of 4- tri- (1- carbodithioic acid base) piperazinyl -1,3,5- triazine sylvite (compound 5):
Using 50mL sealing straight reaction tube as container, by compound 4 (1.20g, 3.60mmol) and KOH (0.5g,
It 8.93mmol) is dissolved in 20mL alcohol solvent and in logical stirred under nitrogen mixed liquor, mixed liquor is warming up to 40 DEG C of reaction 12h,
CS is added under air-proof condition again2(1mL, 15mmol), the reaction was continued for 24 hours, is after the reaction was completed spin-dried for solvent, and 3~5mL is added
Methanol, ultrasonic dissolution, then 10mL Diethyl ether recrystallization is poured into, obtain target compound 5 (1.94g, the yield of pale yellow powder shape
80%, purity 96%, 262~263 DEG C of fusing point).
Nuclear magnetic resonance spectroscopy is carried out to substance obtained using Nuclear Magnetic Resonance, as a result as follows:
Compound 3:
1H NMR (500MHz, Chloroform-d) δ 3.73 (t, J=5.1Hz, 11H), 3.44 (t, J=5.1Hz,
12H), 1.48 (s, 27H), specific nuclear magnetic resonance spectroscopy spectrogram are shown in Fig. 1；
13C NMR (100MHz, Chloroform-d) δ 165.39,154.80,79.82,67.06,43.03,28.41, tool
Body carbon-13 nmr spectra spectrogram is shown in Fig. 2.
Compound 5:
1H NMR(500MHz,DMSO-d6, 298K) and δ=3.64 (s, 12H), 3.35 (s, 14H), specific hydrogen nuclear magnetic resonance
Spectrum spectrogram is shown in Fig. 3；
13C NMR(100MHz,DMSO-d6) δ 214.60,165.12,49.33,43.21, specific carbon-13 nmr spectra spectrogram
See Fig. 4.
Embodiment 2:
1,3- bis- (1- carbodithioic acid base -4- piperazinyl) -5- (1- pyridyl group -4- piperazinyl) -1,3,5- triazine sylvite
The synthesis of (compound 9):
(1) synthesis of the chloro- 1,3,5- triazine (compound 6) of (1-Boc base -4- the piperazinyl) -5- of 1,3- bis-:
By Cyanuric Chloride (1g, 5.46mmol), 1- piperazine-Boc (1.03g, 5.50mmol), potassium carbonate (3.8g,
It 27.5mmol) is added in 80mL tetrahydrofuran organic solvent, is stirred continuously, mixed liquor is reacted at room temperature, protected in nitrogen
After the lower reaction 48h of shield, it is spin-dried for, washes, filters, dries by vacuum, obtain dry compound 6 (2.34g, yield
88%)；
(2) 1,3- bis- (1-Boc base -4- piperazinyl) -5- (1- pyridyl group -4- piperazinyl) -1,3,5- triazine (compound 7)
Synthesis:
Compound 6 (2.30g, 4.77mmol) is dissolved in Isosorbide-5-Nitrae-dioxane solvent of 50mL, (4- pyridine is sequentially added
Base) -1- piperazine (0.80g 4.91mol), K2CO3 (1.97g, 14.31mol), it is stirred continuously, is warming up in a nitrogen atmosphere
110 DEG C of reflux after reacting 48h, are spin-dried for by vacuum, wash, filtering, drying and obtain dry compound 7 (2.36g, yield
81%)；
(3) 1,3- bis- (1- hydrogen -4- piperazinyl) -5- (1- pyridyl group -4- piperazinyl) -1,3,5- triazine (compound 8)
Synthesis:
And the synthesis step of compound 4 is identical as post processing mode, and difference is, with compound 7 (2.3g, 3.77mmol)
For reactant, 50 DEG C of progress back flow reactions are warming up to, by reaction and after purification, obtain compound 8 (1.31g, yield 85%)；
(4) 1,3- bis- (1- carbodithioic acid base -4- piperazinyl) -5- (1- pyridyl group -4- piperazinyl) -1,3,5- triazine potassium
The synthesis of salt (compound 9):
And the synthesis step of compound 5 is identical as post processing mode, and difference is, with compound 8 (1.3g, 2.04mmol)
It is reactant with KOH (0.68g, 12.2mmol), mixed liquor is warming up to 40 DEG C of reactions, by reaction and after purification, obtains white
The powdered target compound 9 of color (1.04g, yield 80%, purity 92%, 222~223 DEG C of fusing point).
Nuclear magnetic resonance spectroscopy is carried out to substance obtained using Nuclear Magnetic Resonance, as a result as follows:
Compound 6:
1H NMR (500MHz, Chloroform-d) δ 3.82 (s, 8H), 3.51 (s, 8H), 1.53 (d, J=2.0Hz,
18H), specific nuclear magnetic resonance spectroscopy spectrogram is shown in Fig. 5；
13C NMR (100MHz, Chloroform-d) δ 165.39,154.80,79.82,43.03,28.41, specific nuclear-magnetism
Resonance carbon spectrum spectrogram is shown in Fig. 6；
Mass spectrum: ESI-MS (CH3OH) m/z:[M+H]+,calcd for C21H34ClN7O4 +,483.24；Found, 484.6,
Specific mass spectrogram is shown in Fig. 7.
Compound 7:
13C NMR (100MHz, Chloroform-d) δ 165.35 (d, J=3.9Hz), 154.81,149.33,108.25,
79.91,45.81,42.74 (d, J=79.0Hz), 28.42, specific carbon-13 nmr spectra spectrogram is shown in Fig. 8.
Compound 8:
1H NMR(500MHz,DMSO-d6) δ 14.02 (s, 1H), 9.69 (s, 4H), 8.29 (t, J=5.4Hz, 2H), 7.25
(dd, J=14.6,7.0Hz, 2H), 4.18-3.87 (m, 12H), 3.09 (s, 8H), specific nuclear magnetic resonance spectroscopy spectrogram are shown in Fig. 9；
13C NMR(100MHz,DMSO-d6) δ 165.11,157.09,140.22 (d, J=38.3Hz), 108.22 (d, J=
66.3Hz), 45.75,42.75, specific carbon-13 nmr spectra spectrogram is shown in Figure 10；
Mass spectrum: ESI-MS (CH3OH) m/z:[M+H]+, calcd for C20H30N10 +,410.27；Found, 411, specifically
Mass spectrogram is shown in Figure 11.
Compound 9:
1H NMR(500MHz,DMSO-d6) δ 8.20 (dd, J=6.0,2.5Hz, 2H), 7.01-6.73 (m, 2H), 4.41
(p, J=3.0Hz, 9H), 3.85 (dd, J=7.1,3.6Hz, 4H), 3.69 (p, J=3.1Hz, 9H), 3.41 (d, J=5.6Hz,
4H), specific nuclear magnetic resonance spectroscopy spectrogram is shown in Figure 12.
Embodiment 3:
1,3- bis- (1- carbodithioic acid base -4- piperazinyl) -5- (N, N- diallyl) -1,3,5- triazine (compound 12)
Synthesis:
(1) conjunction of 1,3- bis- (1-Boc base -4- piperazinyl) -5- (N, N- diallyl) -1,3,5- triazine (compound 10)
At:
And the synthesis step of compound 7 is identical as post processing mode, and difference is, with compound 6 (1g, 2.07mmol),
Diallylamine (1.3mL, 10mmol), K2CO3(1.38g, 10mmol) is reactant, is warming up to 110 DEG C of progress back flow reactions, is passed through
Reaction is crossed with after purification, obtains compound 10 (0.93g, yield 82%)；
(2) 1,3- bis- (1- hydrogen -4- piperazinyl) -5- (N, N- diallyl) -1,3,5- triazine hydrochloride (compound 11)
Synthesis:
And the synthesis step of compound 4 is identical as post processing mode, and difference is, with compound 10 (0.9g,
1.65mmol) be reactant, be warming up to 50 DEG C of progresss back flow reactions, by reaction with after purification, obtain compound 11 (0.49g,
Yield 85%)；
(3) 1,3- bis- (1- carbodithioic acid base -4- piperazinyl) -5- (N, N- diallyl) -1,3,5- triazine (compound
12) synthesis:
And the synthesis step of compound 5 is identical as post processing mode, and difference is, with compound 11 (0.49g,
1.41mmol) and KOH (0.4g, 7.10mmol) is reactant, mixed liquor is warming up to 40 DEG C of reactions, by reacting and purifying
Afterwards, the target compound 12 (0.69g, yield 86%, purity 96%, 205~206 DEG C of fusing point) of white powder is obtained.
Nuclear magnetic resonance spectroscopy is carried out to substance obtained using Nuclear Magnetic Resonance, as a result as follows:
Compound 10:
1H NMR(500MHz,DMSO-d6) δ 9.58 (s, 4H), 3.94 (t, J=5.1Hz, 8H), 3.60 (dq, J=12.0,
6.7Hz, 8H), 3.46 (q, J=7.0Hz, 2H), 3.20-3.00 (m, 8H), 1.08 (t, J=7.0Hz, 2H) .3.35 (s,
17H), 1.44 (s, 19H), specific nuclear magnetic resonance spectroscopy spectrogram are shown in Figure 13.
Compound 12:
1H NMR(500MHz,DMSO-d6) δ 5.82 (brs, 2H), 5.11 (t, J=13.7Hz, 4H), 4.35 (t, J=
5.3Hz, 8H), 4.09 (d, J=5.7Hz, 4H), 3.62 (t, J=5.3Hz, 8H), specific nuclear magnetic resonance spectroscopy spectrogram are shown in Figure 14；
13C NMR(100MHz,DMSO-d6)δ214.73,194,165.28,165.09,134.98,116.80,66.51,
49.33,48.51,43.21,42.40, specific carbon-13 nmr spectra spectrogram is shown in Figure 15.
Embodiment 4:
1,3- bis- (1- carbodithioic acid base -4- piperazinyl) -5- (N, N- bis- (1- ethylene glycol) -1,3,5- triazine sylvite
The synthesis of (compound 15):
(1) 1,3- bis- (1-Boc base -4- piperazinyl) -5- (N, N- bis- (1- ethylene glycol) -1,3,5- triazine (compound
13) synthesis:
And the synthesis step of compound 7 is identical as post processing mode, and difference is, with compound 6 (1g, 2.07mmol),
Diethanol amine (2mL, 20.7mmol), K2CO3(1.38g, 10mmol) is reactant, is warming up to 110 DEG C of progress back flow reactions, is passed through
Reaction is crossed with after purification, obtains compound 13 (1.01g, yield 88%)；
(2) 1,3- bis- (1- hydrogen -4- piperazinyl) -5- ((1- the ethylene glycol) -1,3,5- triazine of N, N- bis- (compound 14)
Synthesis:
And the synthesis step of compound 4 is identical as post processing mode, and difference is, with compound 13 (1.0g,
It is 1.81mmol) reactant, is warming up to 50 DEG C of progress back flow reactions, by reaction and after purification, obtains compound 14
(0.568g, yield 89%)；
(3) 1,3- bis- (1- carbodithioic acid base -4- piperazinyl) -5- (N, N- bis- (1- ethylene glycol) -1,3,5- triazine potassium
The synthesis of salt (compound 15):
And the synthesis step of compound 5 is identical as post processing mode, and difference is, with compound 14 (0.56g,
1.60mmol) and KOH (0.54g, 9.6mmol) is reactant, mixed liquor is warming up to 40 DEG C of reactions, by reacting and purifying
Afterwards, the target compound 15 (0.79g, yield 85%, purity 96%, 202~203 DEG C of fusing point) of white powder is obtained.
Nuclear magnetic resonance spectroscopy is carried out to substance obtained using Nuclear Magnetic Resonance, as a result as follows:
Compound 13:
1H NMR(500MHz,Chloroform-d)δ4.52(s,2H),3.89(s,5H),3.75(s,12H),3.48(s,
8H), 1.49 (s, 18H), specific nuclear magnetic resonance spectroscopy spectrogram are shown in Figure 16；
13C NMR(100MHz,Chloroform-d)δ167.05,164.40,154.70,80.00,62.79,51.28,
43.17,28.39, specific carbon-13 nmr spectra spectrogram is shown in Figure 17.
Compound 14:
1H NMR(500MHz,DMSO-d6) δ 9.58 (s, 4H), 3.94 (t, J=5.1Hz, 8H), 3.60 (dq, J=12.0,
6.7Hz, 8H), 3.46 (q, J=7.0Hz, 2H), 3.20-3.00 (m, 8H), specific nuclear magnetic resonance spectroscopy spectrogram are shown in Figure 18.
Compound 15:
1H NMR(500MHz,DMSO-d6) δ 4.71 (s, 2H), 4.47-4.27 (m, 8H), 3.61 (t, J=5.3Hz, 8H),
3.56 (s, 8H), specific nuclear magnetic resonance spectroscopy spectrogram are shown in Figure 19；
13C NMR(100MHz,DMSO-d6) δ 214.69,194.22,165.09,59.54 (d, J=12.1Hz), 50.93
(d, J=55.56Hz), 49.30 (d, J=70.76Hz), 42.83 (d, J=102.9Hz), specific carbon-13 nmr spectra spectrogram are shown in
Figure 20.
Embodiment 5:
1,3- bis- (3- acrylic-amino) -5- (1- carbodithioic acid base 4- piperazinyl) -1,3,5- triazine sylvite (compound
19) synthesis:
(1) synthesis of the chloro- 1,3,5- triazine (compound 16) of 2- (1-Boc base -4- piperazinyl) -4,6-:
And the synthesis step of compound 3 is identical as post processing mode, and difference is, with Cyanuric Chloride (1g, 5.43mmol),
1- piperazine-Boc (1.03g, 5.50mmol), potassium carbonate (3.8g, 27.5mmol) are reactant, and mixed liquor is carried out at -5 DEG C
Reaction, by after purification, obtaining compound 16 (1.537g, yield 85%).The compound easily hydrolyzes at room temperature, directly into
Row reacts in next step；
(2) synthesis of 1,3- bis- (3- acrylic-amino) -5- (1-Boc base 4- piperazinyl) -1,3,5- triazine (compound 17):
And the synthesis step of compound 7 is identical as post processing mode, and difference is, with compound 16 (1.0g,
3.00mmol), allylamine (2.4mL, 54.30mmol), K2CO3(3.06g, 22.2mmol) be reactant, be warming up to 110 DEG C into
Row back flow reaction obtains compound 17 (1.47g, yield 82%) by reaction and after purification；
(3) synthesis of 1,3- bis- (3- acrylic-amino) -5- (1 hydrogen -4- piperazinyl) -1,3,5- triazine (compound 18):
And the synthesis step of compound 4 is identical as post processing mode, and difference is, with compound 17 (1.4g,
3.59mmol) be reactant, be warming up to 50 DEG C of progresss back flow reactions, by reaction with after purification, obtain compound 18 (0.80g,
Yield 81%)；
(4) 1,3- bis- (3- acrylic-amino) -5- (1- carbodithioic acid base 4- piperazinyl) -1,3,5- triazine sylvite (chemical combination
Object 19) synthesis:
And the synthesis step of compound 5 is identical as post processing mode, and difference is, with compound 18 (0.80g,
2.9mmol) and KOH (0.54g, 9.6mmol) is reactant, and mixed liquor is warming up to 40 DEG C of reactions, by reaction and after purification,
Obtain the target compound 19 (0.90g, yield 80%, purity 93%, 200~201 DEG C of fusing point) of white powder.
Nuclear magnetic resonance spectroscopy is carried out to substance obtained using Nuclear Magnetic Resonance, as a result as follows:
Compound 17:
1H NMR (500MHz, Chloroform-d) δ 5.15 (dd, J=52.6,13.7Hz, 5H), 4.91 (s, 2H),
4.00 (s, 5H), 3.73 (s, 6H), 3.43 (s, 5H), 1.88 (s, 2H), specific nuclear magnetic resonance spectroscopy spectrogram are shown in Figure 21.
Compound 18:
1H NMR (500MHz, Chloroform-d) δ 5.21 (d, J=17.1Hz, 2H), 5.10 (d, J=10.3Hz,
2H), 4.91 (s, 2H), 4.00 (s, 4H), 3.73 (s, 4H), 3.43 (s, 4H), 1.88 (s, 1H), specific nuclear magnetic resonance spectroscopy spectrum
Figure is shown in Figure 22.
Compound 19:
1H NMR(500MHz,DMSO-d6) δ 6.84 (d, J=65Hz, 2H), 5.96-5.75 (m, 2H), 5.24-5.04 (m,
2H), 5.01 (d, J=10.3Hz, 2H), 4.34 (t, J=5.4Hz, 4H), 3.84 (t, J=5.8Hz, 4H), 3.60 (s, 4H),
Specific nuclear magnetic resonance spectroscopy spectrogram is shown in Figure 23；
13C NMR(100MHz,DMSO-d6)δ220.96,172.25,142.99,121.21,72.55,55.44,49.17,
21.07, specific carbon-13 nmr spectra spectrogram is shown in Figure 24；
Mass spectrum: ESI-MS (CH3OH) m/z:[M-K+Na+H]+,calcd for C14H20NaN7S2+,389.09；found,
376.1, specific mass spectrogram is shown in Figure 25.
It should be noted that the above various embodiments belongs to same inventive concept, the description of each embodiment emphasizes particularly on different fields,
Not detailed place is described in separate embodiment, can refer to the description in other embodiments.
Embodiments of the present invention above described embodiment only expresses, the description thereof is more specific and detailed, but can not
Therefore it is construed as limiting the scope of the patent.It should be pointed out that for those of ordinary skill in the art,
Under the premise of not departing from present inventive concept, various modifications and improvements can be made, and these are all within the scope of protection of the present invention.
Therefore, the scope of protection of the patent of the invention shall be subject to the appended claims.
Claims (10)
1. a kind of more two thiocarbohydrazone derivatives of piperazines of triazine radical, which is characterized in that it has the following structure formula:
Wherein, R1And R2Independently of each other, the R1And R2It is respectively selected from A1, A2, A3, A4 or A5:
2. a kind of synthetic method of the more two thiocarbohydrazone derivatives of piperazines of triazine radical as described in claim 1, feature
It is, includes the following steps:
S1,1- piperazine-Boc, Cyanuric Chloride ,-R1With-R2Substitution reaction occurs for substituent group, generates intermediate c；
Hydrolysis occurs for S2, the intermediate c and hydrochloric acid, takes off-Boc base, obtains intermediate d；
S3, the intermediate d and CS2Thiocarboxylic's reaction occurs, obtains finished product.
3. the synthetic method of the more two thiocarbohydrazone derivatives of piperazines of triazine radical according to claim 2, feature exist
In, be also added into the first alkali and the first organic solvent in the step S1, first alkali be sodium carbonate, potassium carbonate, triethylamine,
One of DMAP, sodium bicarbonate, saleratus are a variety of；The molar ratio of first alkali and Cyanuric Chloride is 1~10:1；Institute
Stating the first organic solvent is one of tetrahydrofuran, methanol, ethyl alcohol, dioxane, methylene chloride or a variety of.
4. the synthetic method of the more two thiocarbohydrazone derivatives of piperazines of triazine radical according to claim 2, feature exist
In the temperature of substitution reaction is -5~150 DEG C in the step S1.
5. the synthetic method of the more two thiocarbohydrazone derivatives of piperazines of triazine radical according to claim 2, feature exist
In the molar ratio of hydrochloric acid and the intermediate c are 1~4:1 in the step S2.
6. the synthetic method of the more two thiocarbohydrazone derivatives of piperazines of triazine radical according to claim 2, feature exist
In temperature 50 C~90 DEG C of hydrolysis in the step S2, the reaction time is 8~48h.
7. the synthetic method of the more two thiocarbohydrazone derivatives of piperazines of triazine radical according to claim 2, feature exist
In being also added into the second alkali and third organic solvent in the step S3, the second alkali is sodium hydroxide, potassium hydroxide, hydroxide
One of lithium is a variety of；The molar ratio of second alkali and the intermediate d are 2~10:1；The third organic solvent is
One of methanol, ethyl alcohol, normal propyl alcohol, isopropanol are a variety of.
8. the synthetic method of the more two thiocarbohydrazone derivatives of piperazines of triazine radical according to claim 2, feature exist
In the reaction temperature that thiocarboxylic reacts in the step S3 is 20~60 DEG C.
9. the synthetic method of the more two thiocarbohydrazone derivatives of piperazines of triazine radical according to claim 2, feature exist
In the CS2Molar ratio with the intermediate d is 3~10:1.
10. a kind of more two thiocarbohydrazone derivatives of piperazines of triazine radical as described in claim 1 are in heavy metal ion fluorescence
Application in terms of probe, OLED luminescent material, VOCs fluorescent optical sensor and supermolecule photoswitch.
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| US20020019389A1 (en) * | 2000-06-15 | 2002-02-14 | Chaconne Nsi Co., Ltd. | Urea derivative useful as an anti-cancer agent and process for preparing same |
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