CN103739594A - Schiff base derivatives containing pyrazine ring and triazole structure and preparation method of the derivatives - Google Patents
Schiff base derivatives containing pyrazine ring and triazole structure and preparation method of the derivatives Download PDFInfo
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- 239000002262 Schiff base Substances 0.000 title claims abstract description 18
- 125000001425 triazolyl group Chemical group 0.000 title claims abstract 6
- 238000002360 preparation method Methods 0.000 title abstract description 26
- 150000004753 Schiff bases Chemical class 0.000 title abstract description 11
- 125000003373 pyrazinyl group Chemical group 0.000 title abstract description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 75
- 235000019441 ethanol Nutrition 0.000 claims description 27
- 229960004756 ethanol Drugs 0.000 claims description 24
- 239000007787 solid Substances 0.000 claims description 23
- 238000003756 stirring Methods 0.000 claims description 21
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 18
- 239000012074 organic phase Substances 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 238000010992 reflux Methods 0.000 claims description 9
- 239000012065 filter cake Substances 0.000 claims description 7
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- 238000000605 extraction Methods 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 6
- 238000001953 recrystallisation Methods 0.000 claims description 6
- 238000010792 warming Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 5
- 239000003921 oil Substances 0.000 claims description 5
- 150000002148 esters Chemical class 0.000 claims description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- 229960000583 acetic acid Drugs 0.000 claims description 3
- 239000012043 crude product Substances 0.000 claims description 3
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 239000012362 glacial acetic acid Substances 0.000 claims description 3
- 238000002386 leaching Methods 0.000 claims description 3
- NIPZZXUFJPQHNH-UHFFFAOYSA-N pyrazine-2-carboxylic acid Chemical compound OC(=O)C1=CN=CC=N1 NIPZZXUFJPQHNH-UHFFFAOYSA-N 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 235000002639 sodium chloride Nutrition 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 238000010025 steaming Methods 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 150000003935 benzaldehydes Chemical class 0.000 claims description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 2
- 239000000047 product Substances 0.000 claims description 2
- 239000003814 drug Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 description 19
- -1 triazole compound Chemical class 0.000 description 17
- 150000003852 triazoles Chemical group 0.000 description 13
- 239000000843 powder Substances 0.000 description 12
- 101100391174 Dictyostelium discoideum forC gene Proteins 0.000 description 5
- 239000002585 base Substances 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 2
- ZWDVQMVZZYIAHO-UHFFFAOYSA-N 2-fluorobenzaldehyde Chemical compound FC1=CC=CC=C1C=O ZWDVQMVZZYIAHO-UHFFFAOYSA-N 0.000 description 2
- 230000000259 anti-tumor effect Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 description 2
- 150000003216 pyrazines Chemical class 0.000 description 2
- WJUFSDZVCOTFON-UHFFFAOYSA-N veratraldehyde Chemical compound COC1=CC=C(C=O)C=C1OC WJUFSDZVCOTFON-UHFFFAOYSA-N 0.000 description 2
- 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 1
- 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 1
- ZPQOPVIELGIULI-UHFFFAOYSA-N 1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1 ZPQOPVIELGIULI-UHFFFAOYSA-N 0.000 description 1
- SUYSQRHNTDVWKJ-UHFFFAOYSA-N 1,3-dichlorobenzene;formaldehyde Chemical compound O=C.ClC1=CC=CC(Cl)=C1 SUYSQRHNTDVWKJ-UHFFFAOYSA-N 0.000 description 1
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical class N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 description 1
- WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 description 1
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 description 1
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 description 1
- BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 1
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- BFDOQXWGUPSPDV-AUEPDCJTSA-N CN(CCc1ccc(/C=N/N(C(c2nccnc2)=NN2)C2=S)cc1)[IH][IH]N[IH]I Chemical compound CN(CCc1ccc(/C=N/N(C(c2nccnc2)=NN2)C2=S)cc1)[IH][IH]N[IH]I BFDOQXWGUPSPDV-AUEPDCJTSA-N 0.000 description 1
- 102000016938 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 235000014493 Crataegus Nutrition 0.000 description 1
- 241001092040 Crataegus Species 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000002082 anti-convulsion Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical class 0.000 description 1
- 150000007857 hydrazones Chemical class 0.000 description 1
- 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 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000007721 medicinal effect Effects 0.000 description 1
- 239000002184 metal Chemical class 0.000 description 1
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 1
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 150000007659 semicarbazones Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 231100000167 toxic agent Toxicity 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 201000008827 tuberculosis Diseases 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The objective of the invention is to provide Schiff base derivatives containing a pyrazine ring and a triazole structure and a preparation method of the derivatives. The Schiff base derivatives and the preparation method thereof are characterized in that: the derivatives have the Schiff base structure common in many medicines, and the structure is important as a support group or a pharmacophore group and is widely applied; based on this, the pyrazine ring and the triazole structure are introduced through a reasonable molecular design; and the Schiff base derivatives are novel and will provide novel directions for research in the medical chemistry field.
Description
Technical field
The present invention relates to a class containing Schiff bases derivative and the method for making thereof of pyrazine ring and triazole structure.
Background technology
Pyrazine compounds was synthesized by people first in 1888, and many compounds containing pyrazine ring have important physiologically active, pyrazine compounds is main on medicine plays tuberculosis, drive rich worm, anticonvulsion, antibacterial, remove the vital role such as free radical.
Triazole and derivative thereof are the important nitrogenous compounds of a class.The Philiph-Duphe of middle nineteen sixties Holland company successfully develop first 1,2, the spirit of 4-triazole class sterilant-Wei bacterium, the biological activity that itself has has caused attention and the research of height, and the aspects such as sterilization, weeding, desinsection, agricultural chemicals are are extensively researched and developed and be applied to the triazole compound more afterwards with efficient sterilizing activity.In mid-term in last century, people find that in the research of triazole amino triazole has significant restraining effect to the catalase of mammalian cell, by increasing H in cell
2o
2level and produce cytotoxicity, for this reason, triazole has obtained broad research as potential cell toxicant antitumor drug.
Schiff bases compound and metal complexes thereof are in the important application in medical science, catalysis, analytical chemistry, corrosion and photochromic field.At medical field, that Schiff's base has is antibacterial, sterilization, antitumor, antiviral biological activity.Because some Schiff's base has special physiologically active, in recent years, more and more cause the attention of the world of medicine.It is reported, that the title complex of amino acids, semicarbazone class, contracting amine, heterocyclic, hydrazone class Schiff's base and application thereof has is antibacterial, sterilization, unique medicinal effect such as antitumor, antiviral.
Based on above research, we have synthesized a series of Schiff bases derivatives containing pyrazine ring and triazole structure, this compounds provides potential skeleton structure for the work of carrying out rational molecular designing and screen novel active molecule from natural bioactivity substance, introduce the design of pyrazine ring and triazole, the research for New Schiff Base compounds in medical chemistry field has important theory value.
Summary of the invention
The object of this invention is to provide a class novel Schiff bases derivative and method for making thereof containing pyrazine ring and triazole structure.
Technical scheme of the present invention is as follows:
One class is containing the Schiff bases derivative of pyrazine ring and triazole structure, and it has following general formula:
In formula, R is:
Prepare a class claimed in claim 1 containing a method for the Schiff bases derivative of pyrazine ring and triazole structure, it is characterized in that it is comprised of the following step:
Step 1. is by 10mmol 2-pyrazine carboxylic acid, and 15mL ethanol is placed in the round-bottomed flask with reflux, stirs the lower 40 μ L vitriol oils that slowly drip, oil bath heating, and back flow reaction 10-12h at 90 ℃, adds suitable quantity of water after reaction system concentrating under reduced pressure is removed to ethanol.With ethyl acetate 10mL extraction three times, merge organic phase again, and wash three times with saturated aqueous common salt 10mL.Finally organic phase concentrating under reduced pressure can be obtained to oily liquids product.
Step 2. is dissolved in 15mL ethanol by the ester of step 1 gained, drips gradually 85% hydrazine hydrate 0.6mL under stirring, is warming up to 90 ℃ of stirring and refluxing 4-6h, and pressure reducing and steaming etoh solvent, then adds water, after solid is separated out, filters and washes with water.Filter cake ethyl alcohol recrystallization post-drying.
Step 3. is dissolved in 25mL ethanol by the KOH of the solid of step 2 gained and 9mmol, drips the CS of 11mmol under stirring at normal temperature
2, there is gradually yellow solid to separate out, stir after 30min, by solid filtering and with after a small amount of washing with alcohol three times, filter cake is dried.
Step 4. is dissolved in 20ml ethanol by the solid of step 3 gained, adds 85% hydrazine hydrate 0.6mL, is warming up to 90 ℃ of stirring and refluxing 4-6h, adds suitable quantity of water after reaction system concentrating under reduced pressure is removed to ethanol.With ethyl acetate 10mL extraction three times, merge organic phase again, will after organic phase concentrating under reduced pressure, can obtain white solid.
Step 5. is dissolved in 20mL ethanol by the substituted benzaldehyde of the solid of step 4 gained and equimolar amount, and drip several Glacial acetic acid and several dripping, stirring at normal temperature 1h, by the solid filtering of separating out, the crude product leaching is obtained to class of the present invention containing the Schiff bases derivative of pyrazine ring and triazole structure with dehydrated alcohol recrystallization.
Advantage of the present invention is: derivative of the present invention has the common schiff base structure of many medicines, and this structure is as supporting group or pharmacophoric group all have very consequence and are widely used; On this basis, by rational molecular designing, introduce pyrazine ring and triazole structure, as novel Schiff bases compound, will provide for the research in medical chemistry field new direction.
Embodiment
By following examples, further describe the present invention, but scope of the present invention is not subject to any restriction of these embodiment.
Embodiment 1:(E)-4-(benzylidene is amino)-3-(pyrazine-2-yl)-1H-1, the preparation of 2,4-triazole-5 (4H)-thioketones (compound 1)
By 10mmol 2-pyrazine carboxylic acid, 15mL ethanol is placed in the round-bottomed flask with reflux, stirs the lower 40 μ L vitriol oils that slowly drip, and back flow reaction 10-12h at 90 ℃ adds suitable quantity of water after reaction system concentrating under reduced pressure is removed to ethanol.With ethyl acetate 10mL extraction three times, merge organic phase again, and wash three times with saturated aqueous common salt 10mL.Organic phase concentrating under reduced pressure can be obtained to the ester of oily.Ester is dissolved in to 15mL ethanol, under stirring, drips gradually 85% hydrazine hydrate 0.6mL, be warming up to 90 ℃ of stirring and refluxing 4-6h, after pressure reducing and steaming etoh solvent, add water, after solid is separated out, filter and wash with water.Filter cake ethyl alcohol recrystallization post-drying.The KOH of solid and 9mmol is dissolved in to 25mL ethanol, under stirring at normal temperature, drips the CS of 11mmol
2, there is gradually yellow solid to separate out, stir after 30min, by solid filtering and with after a small amount of washing with alcohol three times, filter cake is dried.Filter cake is dissolved in to 20ml ethanol, adds 85% hydrazine hydrate 0.6mL, be warming up to 90 ℃ of stirring and refluxing 4-6h, add suitable quantity of water after reaction system concentrating under reduced pressure is removed to ethanol.With ethyl acetate 10mL extraction three times, merge organic phase again, will after organic phase concentrating under reduced pressure, can obtain white solid.The phenyl aldehyde of white solid and equimolar amount is dissolved in to 20mL ethanol, and drips several Glacial acetic acid and several dripping, stirring at normal temperature 1h, by the solid filtering of separating out, obtains target compound by the crude product leaching with dehydrated alcohol recrystallization.White powder, productive rate 81%, mp:201-203 ℃;
1h NMR (CDCl
3, 300MHz) δ: 7.21-7.26 (m, 3H), 7.73-7.77 (m, 2H), 8.30 (s, 1H), 8.56 (s, 1H), 8.82 (s, 1H), 9.52 (s, 1H), 10.63 (s, 1H) .MS (ESI): 283.07 (C
13h
11n
6s, [M+H]
+) .Anal.Calcd for C
13h
10n
6s:C, 55.30; H, 3.57; N, 29.77.Found:C, 55.44; H, 3.57; N, 29.73.
Embodiment 2:(E)-4-((2-fluorine benzylidene) amino)-3-(pyrazine-2-yl)-1H-1, the preparation of 2,4-triazole-5 (4H)-thioketones (compound 2)
Preparation method is with embodiment 1.With o fluorobenzaldehyde, replace phenyl aldehyde, obtain target compound.White powder, productive rate 75%, mp:195-197 ℃;
1h NMR (CDCl
3, 300MHz) δ: 7.31-7.33 (m, 2H), 7.67-7.71 (m, 2H), 8.36 (s, 1H), 8.56 (s, 1H), 8.82 (s, 1H), 9.51 (s, 1H), 10.69 (s, 1H) .MS (ESI): 301.06 (C
13h
10fN
6s, [M+H]
+) .Anal.Calcd for C
13h
9fN
6s:C, 51.99; H, 3.02; N, 27.98.Found:C, 52.11; H, 3.02; N, 27.92.
Embodiment 3:(E)-4-((3-fluorobenzene methylene radical) amino)-3-(pyrazine-2-yl)-1H-1, the preparation of 2,4-triazole-5 (4H)-thioketones (compound 3)
Preparation method is with embodiment 1.With a fluorobenzaldehyde, replace phenyl aldehyde, obtain target compound.White powder, productive rate 78%, mp:213-216 ℃;
1h NMR (CDCl
3, 300MHz) δ: 7.20-7.24 (m, 2H), 7.71-7.75 (m, 2H), 8.32 (s, 1H), 8.55 (s, 1H), 8.80 (s, 1H), 9.53 (s, 1H), 10.69 (s, 1H) .MS (ESI): 301.06 (C
13h
10fN
6s, [M+H]
+) .Anal.Calcd for C
13h
9fN
6s:C, 51.99; H, 3.02; N, 27.98.Found:C, 51.88; H, 3.02; N, 27.94.
Embodiment 4:(E)-4-((4-chlorine benzylidene) amino)-3-(pyrazine-2-yl)-1H-1, the preparation of 2,4-triazole-5 (4H)-thioketones (compound 4)
Preparation method is with embodiment 1.With 4-chloro-benzaldehyde, replace phenyl aldehyde, obtain target compound.White powder, productive rate 77%, mp:242-244 ℃;
1h NMR (CDCl
3, 300MHz) δ: 7.39-7.53 (m, 2H), 7.75-7.77 (d, J=8.43Hz, 1H), 8.36 (s, 1H), 8.56 (s, 1H), 8.82 (s, 2H), 9.51 (s, 1H), 10.69 (s, 1H) .MS (ESI): 317.03 (C
13h
10clN
6s, [M+H]
+) .Anal.Calcd forC
13h
9clN
6s:C, 49.29; H, 2.86; N, 26.53.Found:C, 49.41; H, 2.86; N, 26.48.
Embodiment 5:(E)-4-((4-bromobenzene methylene radical) amino)-3-(pyrazine-2-yl)-1H-1, the preparation of 2,4-triazole-5 (4H)-thioketones (compound 5)
Preparation method is with embodiment 1.With p-bromobenzaldehyde, replace phenyl aldehyde, obtain target compound.White powder, productive rate 79%, mp:227-230 ℃;
1h NMR (CDCl
3, 300MHz) δ: 7.33-7.38 (m, 2H), 7.66-7.72 (m, 2H), 8.63 (s, 1H), 8.79-8.80 (m, 1H), (8.93-8.94 d, J=2.4Hz, 1H), 9.27 (s, 1H), 12.35 (s, 1H) .MS (ESI): 360.98 (C
13h
10brN
6s, [M+H]
+) .Anal.Calcd for C
13h
9brN
6s:C, 43.23; H, 2.51; N, 23.27.Found:C, 43.37; H, 2.51; N, 23.31.
Embodiment 6:(E)-4-((2,4 dichloro benzene base) amino)-3-(pyrazine-2-yl)-1H-1, the preparation of 2,4-triazole-5 (4H)-thioketones (compound 6)
Preparation method is with embodiment 1.With 2,4 dichloro benzene formaldehyde, replace phenyl aldehyde, obtain target compound.White powder, productive rate 77%, mp:177-179 ℃;
1h NMR (CDCl
3, 300MHz) δ: 7.01-7.07 (m, 1H), 7.33-7.35 (m, 1H), 7.75-7.77 (m, 1H), 8.34 (s, 1H), 8.56 (s, 1H), 8.82 (s, 1H), 9.52 (s, 1H), 10.63 (s, 1H) .MS (ESI): 350.99 (C
13h
9cl
2n
6s, [M+H]
+) .Anal.Calcd for C
13h
8cl
2n
6s:C, 44.46; H, 2.30; N, 23.93.Found:C, 44.41; H, 2.30; N, 23.88.
Embodiment 7:(E)-4-((4-nitrobenzal) amino)-3-(pyrazine-2-yl)-1H-1, the preparation of 2,4-triazole-5 (4H)-thioketones (compound 7)
Preparation method is with embodiment 1.With paranitrobenzaldehyde, replace phenyl aldehyde, obtain target compound.White powder, productive rate 67%, mp:217-220 ℃;
1h NMR (CDCl
3, 300MHz) δ: 7.35-7.37 (m, 2H), 7.72-7.74 (m, 2H), 8.38 (s, 1H), 8.57 (s, 1H), 8.81 (s, 1H), 9.53 (s, 1H), 10.68 (s, 1H) .MS (ESI): 328.05 (C
13h
10n
7o
2s, [M+H]
+) .Anal.Calcd for C
13h
9n
7o
2s:C, 47.70; H, 2,77; N, 29.95.Found:C, 47.85; H, 2.77; N, 29.92.
Embodiment 8:(E)-4-(4-methoxyl group benzylidene) amino)-3-(pyrazine-2-yl)-1H-1, the preparation of 2,4-triazole-5 (4H)-thioketones (compound 8)
Preparation method is with embodiment 1.With aubepine, replace phenyl aldehyde, obtain target compound.White powder, productive rate 70%, mp:182-184 ℃;
1h NMR (CDCl
3, 300MHz) δ: 3.96 (s, 3H), 6.97-7.03 (m, 2H), 7.21-7.26 (m, 2H), 8.28 (s, 1H), 8.56 (s, 1H), 8.80 (s, 1H), 9.52 (s, 1H), 10.64 (s, 1H) .MS (ESI): 313.08 (C
14h
13n
6oS, [M+H]
+) .Anal.Calcd forC
14h
12n
6oS:C, 53.83; H, 3.87; N, 26.91.Found:C, 53.68; H, 3.87; N, 26.88.
Embodiment 9:(E)-4-(3-methoxyl group benzylidene) amino)-3-(pyrazine-2-yl)-1H-1, the preparation of 2,4-triazole-5 (4H)-thioketones (compound 9)
Preparation method is with embodiment 1.With NSC 43794, replace phenyl aldehyde, obtain target compound.White powder, productive rate 72%, mp:188-190 ℃;
1h NMR (CDCl
3, 300MHz) δ: 3.95 (s, 3H), 7.01-7.06 (m, 2H), 7.27-7.33 (m, 2H), 8.26 (s, 1H), 8.55 (s, 1H), 8.82 (s, 1H), 9.51 (s, 1H), 10.62 (s, 1H) .MS (ESI): 313.08 (C
14h
13n
6oS, [M+H]
+) .Anal.Calcd forC
14h
12n
6oS:C, 53.83; H, 3.87; N, 26.91.Found:C, 53.72; H, 3.87; N, 26.96.
Embodiment 10:(E)-4-(2-methoxyl group benzylidene) amino)-3-(pyrazine-2-yl)-1H-1, the preparation of 2,4-triazole-5 (4H)-thioketones (compound 10)
Preparation method is with embodiment 1.With o-methoxybenzaldehyde, replace phenyl aldehyde, obtain target compound.White powder, productive rate 67%, mp:178-181 ℃;
1h NMR (CDCl
3, 300MHz) δ: 3.95 (s, 3H), 6.99-7.04 (m, 2H), 7.26-7.31 (m, 2H), 8.28 (s, 1H), 8.56 (s, 1H), 8.81 (s, 1H), 9.52 (s, 1H), 10.66 (s, 1H) .MS (ESI): 313.08 (C
14h
13n
6oS, [M+H]
+) .Anal.Calcd forC
14h
12n
6oS:C, 53.83; H, 3.87; N, 26.91.Found:C, 53.71; H, 3.87; N, 26.85.
Embodiment 11:(E)-4-(3,4-dimethoxybenzylidenegroup group) amino)-3-(pyrazine-2-yl)-1H-1, the preparation of 2,4-triazole-5 (4H)-thioketones (compound 11)
Preparation method is with embodiment 1.With Veratraldehyde, replace phenyl aldehyde, obtain target compound.White powder, productive rate 73%, mp:172-176 ℃;
1h NMR (CDCl
3, 300MHz) δ: 3.95 (s, 3H), 3.97 (s, 3H), 6.87-7.00 (m, 1H), 7.15-7.19 (m, 1H), 7.56 (s, 1H), 8.26 (s, 1H), 8.56 (s, 1H), 8.81 (s, 1H), 9.51 (s, 1H), 10.61 (s, 1H) .MS (ESI): 343.09 (C
15h
15n
6o
2s, [M+H]
+) .Anal.Calcd for C
15h
14n
6o
2s:C, 52.62; H, 4.12; N, 24.55.Found:C, 52.50; H, 4.12; N, 24.61.
Embodiment 12:(E)-4-(4-methyl benzylidene) amino)-3-(pyrazine-2-yl)-1H-1, the preparation of 2,4-triazole-5 (4H)-thioketones (compound 12)
Preparation method is with embodiment 1.With p-tolyl aldehyde, replace phenyl aldehyde, obtain target compound.White powder, productive rate 78%, mp:249-251 ℃;
1h NMR (CDCl
3, 300MHz) δ: 2.39 (s, 3H), 7.22-7.26 (m, 2H), 7.70-7.79 (m, 2H), 8.31 (s, 1H), 8.55 (s, 1H), 8.81 (s, 1H), 9.52 (s, 1H), 10.63 (s, 1H) .MS (ESI): 297.08 (C
14h
13n
6s, [M+H]
+) .Anal.Calcd forC
14h
12n
6s:C, 56.74; H, 4.08; N, 28.36.Found:C, 56.60; H, 4.08; N, 28.33.
Advantage of the present invention is: derivative of the present invention has the common schiff base structure of many medicines, and this structure is as supporting group or pharmacophoric group all have very consequence and are widely used; On this basis, by rational molecular designing, introduce pyrazine ring and triazole structure, as novel Schiff bases compound, will provide for the research in medical chemistry field new direction.
Claims (2)
1. a class, containing the Schiff bases derivative of pyrazine ring and triazole structure, is characterized in that it has following general formula:
In formula, R is:
2. prepare a class claimed in claim 1 containing a method for the Schiff bases derivative of pyrazine ring and triazole structure, it is characterized in that it is comprised of the following step:
Step 1. is by 10mmol 2-pyrazine carboxylic acid, and 15mL ethanol is placed in the round-bottomed flask with reflux, stirs the lower 40 μ L vitriol oils that slowly drip, oil bath heating, and back flow reaction 10-12h at 90 ℃, adds suitable quantity of water after reaction system concentrating under reduced pressure is removed to ethanol.With ethyl acetate 10mL extraction three times, merge organic phase again, and wash three times with saturated aqueous common salt 10mL.Finally organic phase concentrating under reduced pressure can be obtained to oily liquids product.
Step 2. is dissolved in 15mL ethanol by the ester of step 1 gained, drips gradually 85% hydrazine hydrate 0.6mL under stirring, is warming up to 90 ℃ of stirring and refluxing 4-6h, and pressure reducing and steaming etoh solvent, then adds water, after solid is separated out, filters and washes with water.Filter cake ethyl alcohol recrystallization post-drying.
Step 3. is dissolved in 25mL ethanol by the KOH of the solid of step 2 gained and 9mmol, drips the CS of 11mmol under stirring at normal temperature
2, there is gradually yellow solid to separate out, stir after 30min, by solid filtering and with after a small amount of washing with alcohol three times, filter cake is dried.
Step 4. is dissolved in 20ml ethanol by the solid of step 3 gained, adds 85% hydrazine hydrate 0.6mL, is warming up to 90 ℃ of stirring and refluxing 4-6h, adds suitable quantity of water after reaction system concentrating under reduced pressure is removed to ethanol.With ethyl acetate 10mL extraction three times, merge organic phase again, will after organic phase concentrating under reduced pressure, can obtain white solid.
Step 5. is dissolved in 20mL ethanol by the substituted benzaldehyde of the solid of step 4 gained and equimolar amount, and drip several Glacial acetic acid and several dripping, stirring at normal temperature 1h, by the solid filtering of separating out, the crude product leaching is obtained to class of the present invention containing the Schiff bases derivative of pyrazine ring and triazole structure with dehydrated alcohol recrystallization.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104086497A (en) * | 2014-07-23 | 2014-10-08 | 张远强 | Triazole Schiff base compounds as well as preparation methods and applications of triazole Schiff base compounds |
| CN104086493A (en) * | 2014-07-23 | 2014-10-08 | 张远强 | Compounds with terminally-substituted phenyl triazole Schiff base structures and applications of compounds |
| CN104086494A (en) * | 2014-07-23 | 2014-10-08 | 张远强 | Compounds with terminally-disubstituted methyl triazole Schiff base structures as well as preparation methods and applications of compounds |
| CN104086495A (en) * | 2014-07-23 | 2014-10-08 | 张远强 | Compounds with terminally-disubstituted triazole Schiff base structure as well as preparation methods and applications of compounds |
| CN104086496A (en) * | 2014-07-23 | 2014-10-08 | 张远强 | Antithrombotic compounds as well as preparation methods and applications of antithrombotic compounds |
| CN104098520A (en) * | 2014-07-23 | 2014-10-15 | 张远强 | Phenyl triazole schiff base compound as well as preparation method and application thereof |
| CN104140398A (en) * | 2014-07-23 | 2014-11-12 | 张远强 | Compound of methyl triazole Schiff base structure, and preparation method and applications of compound |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE4127026A1 (en) * | 1991-08-16 | 1993-02-18 | Boehringer Ingelheim Kg | New 3-amino-6-chloro:pyrazine 2-carboxamide derivs. - useful as hypotensive, mucolytic, diuretic and antitumoural drugs |
| CN1161967A (en) * | 1991-02-01 | 1997-10-15 | 默克·夏普-道姆公司 | Preparation method for imidazole derivatives |
| WO2009086303A2 (en) * | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| WO2012080729A2 (en) * | 2010-12-14 | 2012-06-21 | Electrophoretics Limited | CASEIN KINASE 1δ (CK1δ) INHIBITORS |
-
2012
- 2012-10-17 CN CN201210392783.3A patent/CN103739594A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1161967A (en) * | 1991-02-01 | 1997-10-15 | 默克·夏普-道姆公司 | Preparation method for imidazole derivatives |
| DE4127026A1 (en) * | 1991-08-16 | 1993-02-18 | Boehringer Ingelheim Kg | New 3-amino-6-chloro:pyrazine 2-carboxamide derivs. - useful as hypotensive, mucolytic, diuretic and antitumoural drugs |
| WO2009086303A2 (en) * | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| WO2012080729A2 (en) * | 2010-12-14 | 2012-06-21 | Electrophoretics Limited | CASEIN KINASE 1δ (CK1δ) INHIBITORS |
Non-Patent Citations (7)
| Title |
|---|
| FOROUGHIFAR, NASER等: "Efficient and convenient protocol for the synthesis of novel 1,2,4-triazolo[3,4-b][1,3,4]thiadiazines", 《SYNTHETIC COMMUNICATIONS》 * |
| HASSAN, E.等: "Synthesis and antimicrobial testing of certain oxadiazoline and triazole derivatives", 《PHARMAZIE》 * |
| KHALIL, NASSER S. A. M.: "First synthesis and antimicrobial activity of N- and S-α-L-arabinopyranosyl-1,2,4-triazoles", 《NUCLEOSIDES, NUCLEOTIDES & NUCLEIC ACIDS》 * |
| NASSER S. A. M. KHALIL: "Efficient synthesis, structure, and antimicrobial activity of some novel N- and S-b-D-glucosides of 5-pyridin-3-yl-1,2,4-triazoles", 《CARBOHYDRATE RESEARCH》 * |
| SHENOY, G. GAUTHAM等: "Synthesis and in-vitro antimicrobial activity of new 1,2,4-triazoles", 《JOURNAL OF PHARMACY AND PHARMACOLOGY 》 * |
| 丁然等: "有机化合物中氟的微量测定改进", 《中国医药工业杂志》 * |
| 丁然等: "有机化合物中氟的微量测定改进", 《中国医药工业杂志》, vol. 20, no. 12, 31 December 1989 (1989-12-31), pages 547 * |
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