CN103450178A - Coumarin grafted thiazole hydrazone derivatives and preparation method thereof - Google Patents
Coumarin grafted thiazole hydrazone derivatives and preparation method thereof Download PDFInfo
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- -1 thiazole hydrazone derivatives Chemical class 0.000 title claims abstract description 22
- ZYGHJZDHTFUPRJ-UHFFFAOYSA-N coumarin Chemical compound C1=CC=C2OC(=O)C=CC2=C1 ZYGHJZDHTFUPRJ-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 title abstract description 22
- 229960000956 coumarin Drugs 0.000 title abstract 4
- 235000001671 coumarin Nutrition 0.000 title abstract 4
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 12
- 150000002367 halogens Chemical group 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 26
- 239000000843 powder Substances 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 238000001953 recrystallisation Methods 0.000 claims description 8
- 238000004440 column chromatography Methods 0.000 claims description 4
- 239000012043 crude product Substances 0.000 claims description 4
- BRWIZMBXBAOCCF-UHFFFAOYSA-N hydrazinecarbothioamide Chemical compound NNC(N)=S BRWIZMBXBAOCCF-UHFFFAOYSA-N 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 claims description 3
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims description 2
- 229940125904 compound 1 Drugs 0.000 claims description 2
- 229940125782 compound 2 Drugs 0.000 claims description 2
- 229940126214 compound 3 Drugs 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 2
- 230000000630 rising effect Effects 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000010025 steaming Methods 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 abstract 6
- 229910052799 carbon Inorganic materials 0.000 abstract 6
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical class CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 14
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 5
- 244000046052 Phaseolus vulgaris Species 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 229960000935 dehydrated alcohol Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- RAIPHJJURHTUIC-UHFFFAOYSA-N 1,3-thiazol-2-amine Chemical class NC1=NC=CS1 RAIPHJJURHTUIC-UHFFFAOYSA-N 0.000 description 1
- OWBBAPRUYLEWRR-UHFFFAOYSA-N 4-hydroxycoumarin Chemical compound C1=CC=C2OC(O)=CC(=O)C2=C1 OWBBAPRUYLEWRR-UHFFFAOYSA-N 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- VXIXUWQIVKSKSA-UHFFFAOYSA-N benzotetronic acid Natural products C1=CC=CC2=C1OC(=O)C=C2O VXIXUWQIVKSKSA-UHFFFAOYSA-N 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 210000001700 mitochondrial membrane Anatomy 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 239000003642 reactive oxygen metabolite Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses coumarin grafted thiazole hydrazone derivatives. The coumarin grafted thiazole hydrazone derivatives are characterized by having a formula, which is represented in the description. In the formula, R1, R2 are selected from H, alkyl with a carbon number of 1 to 10, cycloalkyl, alkyloxy with a carbon number of 1 to 5, halogen, and halogen substituted alkyl with a carbon number of 1 to 5; R3, R4, and R5 are selected from H, alkyl with a carbon number of 1 to 5, alkyloxy with a carbon number of 1 to 5, halogen, and halogen substituted alkyl with a carbon number of 1 to 5. The invention also discloses a preparation method of the coumarin grafted thiazole hydrazone derivatives, and the preparation method comprises following steps.
Description
Technical field
The present invention relates to class tonka bean camphor grafting thiazole hydrazone analog derivative and preparation method thereof.
Background technology
Tonka bean camphor can produce antitumous effect by the enhancing body immunologic function, there are some researches show, tonka bean camphor can strengthen the effect of scavenger cell, activate and strengthen monocytic quantity, reconcile monocyte and scavenger cell to lymphocytic activation and strengthen interleukin-etc. to bring into play antitumous effect.In recent years, containing the thiazole ring compound, at aspects such as drug research and biology, demonstrate more and more important effect, wherein the aminothiazole compounds has the reason activity than Johnson & Johnson, especially is subject to investigator's attention.The inhibition of the generation of tumour and the apoptotic signal of tumour cell own is closely bound up, so apoptosis plays an important role in the chemotherapy of tumour, and a lot of medicines is all to reach the purpose for the treatment of tumour by the reconstituted cell apoptosis.Excessive ROS (intracellular reactive oxygen species) can induce mitochondrial membrane potential (MMP) collapse, the dead factor in plastosome is discharged, inducing cell death; The accumulation of ROS simultaneously can cause lipid peroxidation, the oxidation inactivation of protein, enzyme and the oxidative damage of DNA.Research shows, tumour cell has the ROS level higher than normal cell, more responsive to the attack of ROS, so the relevant drug development of ROS becomes a focus of antitumor drug research and development.Develop it and there is certain theory significance and actual value, therefore, we design and have synthesized a series of chloro-3-of (E)-4-tonka bean camphor grafting thiazole hydrazone analog derivatives that ((2-(4-phenyl thiazole-2-yl) hydrazono-) methyl)-2H-tonka bean camphor-2-ketone is female ring of take.
Summary of the invention
The object of the present invention is to provide class tonka bean camphor grafting thiazole hydrazone analog derivative and preparation method thereof.
Technical scheme of the present invention is as follows:
1. a class tonka bean camphor grafting thiazole hydrazone analog derivative is characterized in that they have following general formula:
In formula, R
1, R
2be selected from the C1-5 alkyl of hydrogen, C1-10 alkyl, cycloalkyl, C1-5 alkoxyl group, halogen, halogen replacement;
R
3, R
4, R
5be selected from the C1-5 alkyl of H, C1-5 alkyl, C1-5 alkoxyl group, halogen, halogen replacement.
A kind ofly prepare a class tonka bean camphor grafting thiazole hydrazone analog derivative method for making claimed in claim 1, they are become by the following step:
Step 1., in stink cupboard, under cold condition, after adding the organic solvent certain volume in flask, slowly drips the POCl of equal volume
3the compound 1 that will be dissolved in again the equal volume organic solvent is added drop-wise in above-mentioned flask, stirring reaction is after for some time, and the rising temperature, follow the tracks of reaction through TLC, after question response is complete, reaction solution is poured in the frozen water of certain volume, with alkali, regulates the pH value to 5-10, and decompress filter obtains yellow solid, drying, the method by column chromatography or recrystallization obtains yellow powder 2 to its purifying.
Step 2. is mixed compound 2 obtained above and thiosemicarbazide, adds a certain amount of organic solvent dissolution, drips appropriate acid and makees catalyzer, stirring reaction at room temperature, TLC follows the tracks of reaction, after reacting completely, the pressure reducing and steaming organic solvent obtains crude product, and crude product is through the column chromatography yellow powder 3 of purifying to obtain.
Step 3. is by compound 3 obtained above, containing various substituent alpha-brominated methyl phenyl ketones, be dissolved in appropriate organic solvent, follow the tracks of reaction through TLC, the rear removal of solvent under reduced pressure that reacts completely, purifiedly obtain target compound tonka bean camphor grafting thiazole hydrazone analog derivative of the present invention.
Embodiment:
Embodiment mono-: the preparation of the chloro-3-of (E)-4-((2-(4-phenyl thiazole-2-yl) hydrazono-) methyl)-2H-tonka bean camphor-2-ketone
In stink cupboard, under cold condition, add the DMF of 10mL in the 100mL single necked round bottom flask, by 5ml POCl
3slowly drop in flask, then the 4 hydroxy coumarin (2.38g, 12.4mmol) that will be dissolved in 10mL DMF slowly is added drop-wise in flask, after the about 2h of stirring reaction, move to the about 2-3h of reaction under 70 ℃, after reaction finishes, standing after it is cooling, reactant is joined in the 20mL frozen water, use Na
2cO
3or K
2cO
3regulate pH value to neutral, the solid filtering of separating out is dried rear with acetone and anhydrous alcohol solution recrystallization.Get the solid (0.8g that above-mentioned recrystallization goes out, 3.8mmoL) join in the 50mL single necked round bottom flask, adding the 25mL Virahol dissolves, the thiosemicarbazide that adds again 0.35g, the glacial acetic acid that drips 0.25mL is made catalyzer, stirring reaction under room temperature, TLC follows the tracks of reaction, finish reaction after about 24h, evaporated under reduced pressure, obtain yellow solid.Get above-mentioned brown color solid (0.1g, 0.35mmoL) be placed in the single necked round bottom flask of 50mL, adding the 25mL Virahol dissolves, amount (the 67.5mg such as add again, 0.35mmoL) alpha-brominated methyl phenyl ketone, stirring reaction under room temperature, TLC follows the tracks of, react completely after about 24h, the solid obtained is dissolved in to the purification of dehydrated alcohol recrystallization and obtains yellow powder shape target compound.198～199 ℃ of productive rate 78.7%.m.p.
1h NMR (DMSO-d
6, 300MHz) δ: 7.30 (t, J=7.3Hz, 1H), (7.40 t, J=9.2Hz, 3H), 7.49 (t, J=7.2Hz, 2H), 7.71 (t, J=7.8Hz, 1H), 7.87 (d, J=7.3Hz, 2H), 8.02 (d, J=8.4Hz, 1H), 8.23 (s, 1H).
Embodiment bis-: the preparation of the chloro-3-of (E)-4-((2-(4 methoxyl groups-phenyl thiazole-2-yl) hydrazono-) methyl)-2H-tonka bean camphor-2-ketone
The preparation method, with embodiment mono-, replaces alpha-brominated methyl phenyl ketone with 4-methoxyl group-α bromoacetophenone, obtains yellow powder shape target compound.201～203 ℃ of productive rate 69.5%.m.p.
1h NMR (DMSO-d
6, 300MHz) δ: 3.79 (s, 3H), 6.97 (d, J=8.8Hz, 2H), 7.20 (s, 1H), (7.50 t, J=7.2Hz, 2H), 7.70 (t, J=7.8Hz, 1H), 7.79 (d, J=8.8Hz, 1H), 8.03 (d, J=8.0Hz, 1H), 8.22 (s, 1H).
Embodiment tri-: (E)-((2-(4-bromophenyl) thiazol-2-yl) hydrazono-) methyl)-preparation of the chloro-2H-tonka bean camphor of 4--2-ketone
The preparation method, with embodiment mono-, replaces alpha-brominated methyl phenyl ketone with the bromo-alpha-brominated methyl phenyl ketone of 4-, obtains yellow powder shape target compound.244～247 ℃ of productive rate 56.3%.m.p.
1h NMR (DMSO-d
6, 300MHz) δ: 7.41 (t, J=7.8Hz, 3H), 7.52 (d, J=8.6Hz, 2H), 7.66～7.61 (m, 1H), 7.73 (d, J=6.6Hz, 2H), 7.94 (d, J=6.8Hz, 1H), 8.15 (s, 1H), 12.53 (s, 1H).
Embodiment tetra-: the preparation of (E)-3-((2-(4-(2-bromophenyl) thiazol-2-yl) hydrazono-) the methyl)-chloro-2H-tonka bean camphor of 4--2-ketone
The preparation method, with embodiment mono-, replaces alpha-brominated methyl phenyl ketone with the bromo-alpha-brominated methyl phenyl ketone of 2-, obtains yellow powder shape target compound.225～227 ℃ of productive rate 59.2%.m.p.
1h NMR (DMSO-d
6, 300MHz) δ: 7.29 (t, J=7.3Hz, 1H), 7.44～7.38 (m, 4H), 7.66～7.61 (m, 4H), 7.88 (d, J=8.3Hz, 2H), 7.96 (d, J=9.7Hz, 1H), 8.16 (s, 1H).
Embodiment five: the chloro-3-of (E)-4-(preparation of (2-(4-(4-(trifluoromethyl) phenyl-2-yl) hydrazono-) methyl)-2H-tonka bean camphor-2-ketone
The preparation method, with embodiment mono-, replaces alpha-brominated methyl phenyl ketone with 4-trifluoromethyl-alpha-bromoacetophenone, obtains yellow powder shape target compound.246～247 ℃ of productive rate 34.2%.m.p.
1h NMR (DMSO-d
6, 300MHz) δ: 7.37 (t, J=7.3Hz, 1H), 7.46～7.53 (m, 4H), 7.70～7.74 (m, 4H), 7.96 (d, J=8.3Hz, 4H), 8.04 (d, J=6.8Hz, 1H), 8.25 (s, 1H).
Embodiment six: (E)-3-((2-(4-phenyl) thiazol-2-yl) hydrazono-) methyl)-6, and the preparation of the chloro-2H-tonka bean camphor of 8-di-t-butyl-4--2-ketone
In stink cupboard, under cold condition, add the DMF of 10mL in the 100mL single necked round bottom flask, by 5mL POCL
3slowly drop in flask, to be dissolved in again the 4-hydroxyl-2 of 10mL DMF, 8-di-t-butyl tonka bean camphor (3.40g, 12.4mmoL) slowly be added drop-wise in flask, after the about 2h of stirring reaction, move to the about 2-3h of reaction under 70 ℃, after reaction finishes, standing after it is cooling, reactant is joined in the 20mL frozen water, use Na
2cO
3or K
2cO
3regulate pH value to neutral, the solid filtering of separating out is dried rear with acetone and anhydrous alcohol solution recrystallization.Get the solid (1.22g that above-mentioned recrystallization goes out, 3.8mmoL) join in the 50mL single necked round bottom flask, adding the 25mL Virahol dissolves, the thiosemicarbazide that adds again 0.35g, the glacial acetic acid that drips 0.25mL is made catalyzer, stirring reaction under room temperature, TLC follows the tracks of reaction, finish reaction after about 24h, evaporated under reduced pressure, obtain yellow solid.Get above-mentioned yellow solid (0.138g, 0.35mmoL) be placed in the single necked round bottom flask of 50mL, adding the 25mL Virahol dissolves, amount (the 67.5mg such as add again, 0.35mmoL) alpha-brominated methyl phenyl ketone, stirring reaction under room temperature, TLC follows the tracks of, react completely after about 24h, the solid obtained is dissolved in to the purification of dehydrated alcohol recrystallization and obtains yellow crystals shape target compound.Productive rate 34.9%.m.p222-224 ℃.
1h NMR (DMSO-d
6, 300MHz) δ: 1.36 (s, 9H), 1.47 (s, 9H), 7.30 (t, J=4.4Hz, 1H), 7.38～7.42 (m, 3H), 7.65 (s, 1H), 7.86 (s, 3H), 8.24 (s, 1H), 12.56 (s, 1H).
Embodiment seven: (E)-3-((2-(4-(4-methoxyl group-phenyl) thiazol-2-yl) hydrazono-) methyl)-6, the preparation of the chloro-2H-tonka bean camphor of 8-di-t-butyl-4--2-ketone
The preparation method, with embodiment six, replaces alpha-brominated methyl phenyl ketone with 4-methoxyl group-alpha-brominated methyl phenyl ketone, obtains yellow powder shape target compound, 201～203 ℃ of productive rate 68.6%.m.p.
1h NMR (DMSO-d
6, 300MHz) δ: 1.31 (s, 9H), 1.43 (s, 9H), 3.74 (s, 3H), (6.92 d, J=5.1Hz, 2H), 7.13 (s, 1H), 7.60 (s, 1H), (7.74 d, J=5.1Hz, 2H), 7.81 (s, 1H), 8.18 (s, 1H).
Embodiment eight: (E)-3-((2-(4-(4-bromophenyl) thiazol-2-yl) hydrazono-) methyl)-6, the preparation of the chloro-2H-tonka bean camphor of 8-di-t-butyl-4--2-ketone
The preparation method, with embodiment six, replaces alpha-brominated methyl phenyl ketone with the bromo-alpha-brominated methyl phenyl ketone of 4-, obtains yellow powder shape target compound.209～210 ℃ of productive rate 51.5%.m.p.
1h NMR (DMSO-d
6, 300MHz) δ: 1.36 (s, 9H), 1.47 (s, 9H), 7.47 (s, 1H), 7.61 (t, J=10.4Hz, 1H), 7.82 (t, J=10.2Hz, 3H), 8.24 (s, 1H), 12.56 (s, 1H).
Embodiment nine: (E)-6, the chloro-3-of 8-di-t-butyl-4-((2-(4-(4-trifluoromethyl) phenyl) thiazol-2-yl) hydrazono-) methyl)-2H-tonka bean camphor-2-ketone
The preparation method, with embodiment six, replaces alpha-brominated methyl phenyl ketone with 4-trifluoromethyl-alpha-bromoacetophenone, obtains yellow powder shape target compound.210～219 ℃ of productive rate 48.8%.m.p.
1h NMR (DMSO-d
6, 300MHz) δ: 1.36 (s, 9H), 1.47 (s, 9H), 7.64 (d, J=8.0Hz, 2H), 7.76 (d, J=8.3Hz, 1H), 7.84 (d, J=8.0Hz, 2H), 8.08 (t, J=5.8Hz, 2H), 8.26 (s, 1H).
Embodiment ten: (E)-3-((2-(4-(2-bromophenyl) thiazol-2-yl) hydrazono-) methyl)-6, the chloro-2H-tonka bean camphor of 8-di-t-butyl-4--2-ketone
The preparation method, with embodiment six, replaces alpha-brominated methyl phenyl ketone with the bromo-alpha-brominated methyl phenyl ketone of 2-, obtains yellow powder shape target compound, 208～210 ℃ of productive rate 50.8%.m.p.
1h NMR (DMSO-d
6, 300MHz) δ: 1.37 (s, 9H), 1.48 (s, 9H), 7.37 (t, J=8.0Hz, 1H), (7.48 t, J=8.0Hz, 3H), 7.65 (s, 1H), 7.70～7.74 (m, 4H), 7.87 (d, J=3.6Hz, 1H), 7.95 (d, J=8.3Hz, 2H), 8.26 (s, 1H).
Claims (1)
1. a class tonka bean camphor grafting thiazole hydrazone analog derivative is characterized in that they have following general formula:
In formula, R
1, R
2be selected from the C1-5 alkyl of hydrogen, C1-10 alkyl, cycloalkyl, C1-5 alkoxyl group, halogen, halogen replacement;
R
3, R
4, R
5be selected from the C1-5 alkyl of H, C1-5 alkyl, C1-5 alkoxyl group, halogen, halogen replacement.
A kind ofly prepare a class tonka bean camphor grafting thiazole hydrazone analog derivative method for making claimed in claim 1, they are become by the following step:
Step 1., in stink cupboard, under cold condition, after adding the organic solvent certain volume in flask, slowly drips the POCl of equal volume
3the compound 1 that will be dissolved in again the equal volume organic solvent is added drop-wise in above-mentioned flask, stirring reaction is after for some time, and the rising temperature, follow the tracks of reaction through TLC, after question response is complete, reaction solution is poured in the frozen water of certain volume, with alkali, regulates the pH value to 5-10, and decompress filter obtains yellow solid, drying, the method by column chromatography or recrystallization obtains yellow powder 2 to its purifying.
Step 2. is mixed compound 2 obtained above and thiosemicarbazide, adds a certain amount of organic solvent dissolution, drips appropriate acid and makees catalyzer, stirring reaction at room temperature, TLC follows the tracks of reaction, after reacting completely, the pressure reducing and steaming organic solvent obtains crude product, and crude product is through the column chromatography yellow powder 3 of purifying to obtain.
Step 3. is by compound 3 obtained above, containing various substituent alpha-brominated methyl phenyl ketones, be dissolved in appropriate organic solvent, follow the tracks of reaction through TLC, the rear removal of solvent under reduced pressure that reacts completely, purifiedly obtain target compound tonka bean camphor grafting thiazole hydrazone analog derivative of the present invention.
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| CN104945388A (en) * | 2015-07-09 | 2015-09-30 | 南京大学 | Preparing method for 4-(3-(3-(4-clocoumarol)-acylhydrazone)-5-phenyl-pyrazol) benzene sulfonamide derivate and application to anti-cancer drugs |
| CN107382998A (en) * | 2017-09-05 | 2017-11-24 | 河南农业大学 | A kind of fluorine-containing cumarin thiazole compound and its synthetic method |
| CN114213407A (en) * | 2021-12-01 | 2022-03-22 | 江苏海洋大学 | 2-pyridyl thiazole hydrazone coumarin derivative chemical sensor, preparation method and application |
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| CN104817552A (en) * | 2015-05-04 | 2015-08-05 | 吉首大学 | Preparing method of (E)-N'-arylmethylene-4-(coumarin-3-yl)thiazole-2-hydrazide compound and its application |
| CN104817552B (en) * | 2015-05-04 | 2017-06-27 | 吉首大学 | (E) (base of cumarin 3) the hydrazide kind compound preparation method of thiazole 2 of N ' aryl methylenes 4 and purposes |
| CN104945388A (en) * | 2015-07-09 | 2015-09-30 | 南京大学 | Preparing method for 4-(3-(3-(4-clocoumarol)-acylhydrazone)-5-phenyl-pyrazol) benzene sulfonamide derivate and application to anti-cancer drugs |
| CN107382998A (en) * | 2017-09-05 | 2017-11-24 | 河南农业大学 | A kind of fluorine-containing cumarin thiazole compound and its synthetic method |
| CN114213407A (en) * | 2021-12-01 | 2022-03-22 | 江苏海洋大学 | 2-pyridyl thiazole hydrazone coumarin derivative chemical sensor, preparation method and application |
| CN114213407B (en) * | 2021-12-01 | 2023-12-19 | 江苏海洋大学 | Chemical sensor of 2-pyridyl thiazole hydrazone coumarin derivative, preparation method and application |
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