CN103819407A - Green catalytic synthesis method for N-(phenylimino)indazole-1-thioamides - Google Patents
Green catalytic synthesis method for N-(phenylimino)indazole-1-thioamides Download PDFInfo
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- CN103819407A CN103819407A CN201410066913.3A CN201410066913A CN103819407A CN 103819407 A CN103819407 A CN 103819407A CN 201410066913 A CN201410066913 A CN 201410066913A CN 103819407 A CN103819407 A CN 103819407A
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- thioamides
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- 238000000034 method Methods 0.000 title claims abstract description 17
- LPYNXEBBIXNRTN-UHFFFAOYSA-N N-phenyliminoindazole-1-carbothioamide Chemical class C1(=CC=CC=C1)N=NC(=S)N1N=CC2=CC=CC=C12 LPYNXEBBIXNRTN-UHFFFAOYSA-N 0.000 title abstract 3
- 238000007036 catalytic synthesis reaction Methods 0.000 title abstract 2
- 239000002608 ionic liquid Substances 0.000 claims abstract description 26
- 239000003054 catalyst Substances 0.000 claims abstract description 18
- 238000006243 chemical reaction Methods 0.000 claims abstract description 18
- UOFGSWVZMUXXIY-UHFFFAOYSA-N 1,5-Diphenyl-3-thiocarbazone Chemical compound C=1C=CC=CC=1N=NC(=S)NNC1=CC=CC=C1 UOFGSWVZMUXXIY-UHFFFAOYSA-N 0.000 claims abstract description 9
- 150000003934 aromatic aldehydes Chemical class 0.000 claims abstract description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 8
- 238000001816 cooling Methods 0.000 claims abstract description 8
- 239000000741 silica gel Substances 0.000 claims abstract description 8
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 8
- 230000035484 reaction time Effects 0.000 claims abstract description 5
- -1 indazole-1-thioamide analog compound Chemical class 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 14
- 238000006555 catalytic reaction Methods 0.000 claims description 8
- 238000000967 suction filtration Methods 0.000 claims description 8
- 239000007848 Bronsted acid Substances 0.000 claims description 7
- 239000000706 filtrate Substances 0.000 claims description 7
- 238000002390 rotary evaporation Methods 0.000 claims description 7
- 238000001291 vacuum drying Methods 0.000 claims description 7
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 claims description 4
- QVTPWONEVZJCCS-UHFFFAOYSA-N 2-formylbenzonitrile Chemical compound O=CC1=CC=CC=C1C#N QVTPWONEVZJCCS-UHFFFAOYSA-N 0.000 claims description 3
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 claims description 3
- HJSLFCCWAKVHIW-UHFFFAOYSA-N cyclohexane-1,3-dione Chemical compound O=C1CCCC(=O)C1 HJSLFCCWAKVHIW-UHFFFAOYSA-N 0.000 claims description 3
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 claims description 3
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 claims description 2
- SRWILAKSARHZPR-UHFFFAOYSA-N 3-chlorobenzaldehyde Chemical compound ClC1=CC=CC(C=O)=C1 SRWILAKSARHZPR-UHFFFAOYSA-N 0.000 claims description 2
- 235000014493 Crataegus Nutrition 0.000 claims description 2
- 241001092040 Crataegus Species 0.000 claims description 2
- BTFQKIATRPGRBS-UHFFFAOYSA-N o-tolualdehyde Chemical compound CC1=CC=CC=C1C=O BTFQKIATRPGRBS-UHFFFAOYSA-N 0.000 claims description 2
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 11
- 150000002473 indoazoles Chemical class 0.000 abstract description 8
- 230000015572 biosynthetic process Effects 0.000 abstract description 6
- 230000003197 catalytic effect Effects 0.000 abstract description 5
- BADXJIPKFRBFOT-UHFFFAOYSA-N dimedone Chemical compound CC1(C)CC(=O)CC(=O)C1 BADXJIPKFRBFOT-UHFFFAOYSA-N 0.000 abstract description 2
- 239000011831 acidic ionic liquid Substances 0.000 abstract 1
- 238000006065 biodegradation reaction Methods 0.000 abstract 1
- 125000004122 cyclic group Chemical group 0.000 abstract 1
- 238000001914 filtration Methods 0.000 abstract 1
- 239000005457 ice water Substances 0.000 abstract 1
- 238000011031 large-scale manufacturing process Methods 0.000 abstract 1
- 238000005086 pumping Methods 0.000 abstract 1
- 238000000926 separation method Methods 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- RHEMILZGKPGZEU-UHFFFAOYSA-N indazole-1-carbothioamide Chemical class C1=CC=C2N(C(=S)N)N=CC2=C1 RHEMILZGKPGZEU-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical group CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000002994 raw material Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000003513 alkali Substances 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000004064 recycling Methods 0.000 description 4
- 238000006137 acetoxylation reaction Methods 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000002475 indoles Chemical class 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- KAIPKTYOBMEXRR-UHFFFAOYSA-N 1-butyl-3-methyl-2h-imidazole Chemical class CCCCN1CN(C)C=C1 KAIPKTYOBMEXRR-UHFFFAOYSA-N 0.000 description 1
- IBZJNLWLRUHZIX-UHFFFAOYSA-N 1-ethyl-3-methyl-2h-imidazole Chemical class CCN1CN(C)C=C1 IBZJNLWLRUHZIX-UHFFFAOYSA-N 0.000 description 1
- GOSUFRDROXZXLN-UHFFFAOYSA-N 4-phenyl-1,2,4-triazolidine-3,5-dione Chemical compound O=C1NNC(=O)N1C1=CC=CC=C1 GOSUFRDROXZXLN-UHFFFAOYSA-N 0.000 description 1
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 1
- 0 CC(C)(CC1=C2C(C3=CC=C*(*)C=C3)N(c3ccccc3)N1C(N=Nc1ccccc1)=S)CC2=O Chemical compound CC(C)(CC1=C2C(C3=CC=C*(*)C=C3)N(c3ccccc3)N1C(N=Nc1ccccc1)=S)CC2=O 0.000 description 1
- CTENFNNZBMHDDG-UHFFFAOYSA-N Dopamine hydrochloride Chemical compound Cl.NCCC1=CC=C(O)C(O)=C1 CTENFNNZBMHDDG-UHFFFAOYSA-N 0.000 description 1
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 239000002879 Lewis base Substances 0.000 description 1
- 241001136616 Methone Species 0.000 description 1
- HUMNYLRZRPPJDN-UHFFFAOYSA-N O=Cc1ccccc1 Chemical compound O=Cc1ccccc1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 1
- UOFGSWVZMUXXIY-BMRADRMJSA-N S=C(NNc1ccccc1)/N=N/c1ccccc1 Chemical compound S=C(NNc1ccccc1)/N=N/c1ccccc1 UOFGSWVZMUXXIY-BMRADRMJSA-N 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 239000011830 basic ionic liquid Substances 0.000 description 1
- 239000003225 biodiesel Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003433 contraceptive agent Substances 0.000 description 1
- 230000002254 contraceptive effect Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- ZIUSEGSNTOUIPT-UHFFFAOYSA-N ethyl 2-cyanoacetate Chemical compound CCOC(=O)CC#N ZIUSEGSNTOUIPT-UHFFFAOYSA-N 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 150000007527 lewis bases Chemical class 0.000 description 1
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical compound N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
The invention discloses a green catalytic synthesis method for N-(phenylimino)indazole-1-thioamides, which belongs to the technical field of organic synthesis. In a synthetic reaction, a mol ratio of aromatic aldehyde to dithizone to 5,5-dimethyl-1,3-cyclohexanedione is 1: 1: 1, the molar weight of a Mucopolysacchariden Bronsted acidic ionic liquid catalyst is 20 to 50% of that of aromatic aldehyde, reaction temperature is 80 to 100 DEG C, and reaction time is 25 to 60 min; after the reaction, ice water is used for cooling, pumping filtration is carried out, and a filter residue undergoes separation by a silica gel chromatographic column so as to obtain pure N-(phenylimino)indazole-1-thioamides. Compared with other methods using ionic liquid as a catalyst for synthesis of indazoles, the method provided by the invention has the characteristics of good catalytic activity, a small application amount of the catalyst, a small loss amount of the catalyst in cyclic usage of the catalyst, easy biodegradation of the catalyst, convenient industrial large-scale production, etc.
Description
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to the method for synthetic N-(phenylimino) indazole-1-thioamide analog compound of a kind of green catalysis.
Background technology
Indazole is as the bioisostere of indoles, and its many indazole compounds are not only widely used aspect agricultural chemicals, is also the intermediate of the medicines such as preparation antidepressant, anti-inflammatory, Antipyretic, Dopamine HCL antagonism, antitumor, anti AIDS virus and contraception.For example, indazole ring is at Cu
2+under catalysis, can obtain 1-arylindazoles with aromatic yl acid reaction, 1-arylindazoles can be used as contraceptive bian; Indazole and acid anhydrides or acyl chloride reaction can obtain N-acyl group indazole, and some of them N-acyl group indazole has anthelmintic activity.So the synthetic tool of research indazole compounds is of great significance.And preparation method's ubiquity long reaction time of traditional indazole compounds, catalyzer poisonous and harmful, usage quantity are large and the shortcoming such as can not recycle.Therefore a kind of, develop green, efficient, simple synthesis of indole compounds method becomes many organic synthesis worker questions of common concern.
Acid, basic functionalized ionic liquid, comprise lewis acidity ionic liquid, lewis base property ionic liquid, bronsted acid ionic liquid and bronsted alkali ionic liquid, because it has that kind is many, active sites density is high, intensity distribution is even, active sites is difficult for the features such as losss and is applied in the organic synthesis of some important drugs intermediates, but in indazole compounds synthetic, apply less.Such as Hamid Reza Shaterian etc. is at weakly alkaline ionic liquid acetoxylation N-butyl-N-crassitude salt, under acetoxylation 1-butyl-3-methylimidazole salt and the katalysis of acetoxylation 1-ethyl-3-methylimidazole salt, by aromatic aldehyde, 4-phenyl urazole and propane dinitrile or ethyl cyanacetate three components " one kettle way " have been synthesized a series of 7-amino-1, 3-dioxy-1, 2, 3, 5-tetrahydro-pyrazole [1, 2, 4] triazole derivative (Mild basic ionic liquids as catalyst for the multi component synthesis of7-amino-1, 3-dioxo-1, 2, 3, 5-tetrahydropyrazolo[1, 2-a] [1, 2, 4] triazole and6, 6-dimethyl-2-phenyl-9-aryl-6, 7-dihydro-[1, 2, 4] triazolo[1, 2-a] indazole-1, 3, 8 (2H, 5H, 9H)-trione derivatives, Journal of Molecular Liquids, 2013, 183:8-13).Again such as Iraj Mohammadpoor-Baltork etc. utilizes lewis acidity ionic liquid [BPy] [FeCl
4] as a kind of effective catalyst, aldehyde, dithizone and methone are catalyzed and synthesized to N-(phenylimino) indazole-1-thioamide analog compound, the method has advantage (A novel one-pot three component synthesis of N-(phenylimino) indazole-1-carbothioamides such as reaction conditions gentleness, reaction times be short, RSC Advances, 2014,4:2251-2256).
The alkali ionic liquid that aforesaid method adopts all belongs to weakly alkaline ionic liquid, and in the reaction process that catalyzes and synthesizes indazole compounds, catalytic efficiency is poor, and the usage quantity of ionic liquid is also larger.[the BPy] [FeCl adopting
4] belong to lewis acidity ionic liquid, easily there is hydrolysis with the water capacity and cause its structure to change, thereby affect its catalysis and the effect recycling.In addition, the parent of above-mentioned ionic liquid structure is the structure such as imidazoles, pyridine of difficult for biological degradation, and preparation price is higher, and the aim of this and green organic synthesis is contrary, causes it in suitability for industrialized production, to be difficult to be used on a large scale.
Summary of the invention
The object of the invention is to overcome in prior art utilize acid, alkali ionic liquid to catalyze and synthesize in indazole compounds process, to have ionic liquid consumption and recycle middle number of dropouts all very large, catalytic efficiency is undesirable, easily there is the shortcoming such as hydrolysis and unsuitable biological degradation in ionic liquid, and provide, a kind of readily biodegradable, acidity are higher, facile hydrolysis, multi-sulfonic bronsted acid ionic liquid that preparation expense is lower are not made green catalyst, catalyze and synthesize the method for indazole compounds under condition of no solvent.
The structural formula of multi-sulfonic bronsted acid ionic-liquid catalyst used in the present invention (hereinafter to be referred as BAIL) is:
The method of synthetic N-(phenylimino) indazole-1-thioamide analog compound of a kind of green catalysis provided by the present invention, its chemical equation is:
Wherein: aromatic aldehyde in reaction (I), dithizone (II) and 5,5-dimethyl-1, the mol ratio of hydroresorcinol (III) is 1:1:1, the molar weight of BAIL is 20～50% of aromatic aldehyde used, temperature of reaction is 80～100 ℃, reaction times is 25～60min, reaction pressure is a normal atmosphere, after reaction, frozen water is cooling, suction filtration, filter residue separates and obtains pure N-(phenylimino) indazole-1-thioamide analog compound (IV) through silica gel chromatographic column (moving phase is normal hexane: ethyl acetate=4:1).Filtrate (main component is BAIL and water) is repeatedly reusable after rotary evaporation, vacuum-drying first.
The present invention's aromatic aldehyde used is phenyl aldehyde, 4-chloro-benzaldehyde, o-chlorobenzaldehyde, m chlorobenzaldehyde, to phenyl phenyl aldehyde, p-tolyl aldehyde, aubepine, o-tolualdehyde, salicylaldhyde, p-Hydroxybenzaldehyde, to any in cyanobenzaldehyde.
The preparation method of BAIL used in the present invention, is shown in pertinent literature (Synthesis of a novel multi – SO
3h functionalized ionic liquid and its catalytic activities for biodiesel synthesis, Green Chemistry, 12 (2010), 201-204; A preparation method for multi-sulfonic functional ion liquid, CN101348487A).
Compared with the synthetic method that the present invention makes catalyzer with other acid, alkali ionic liquid, have the following advantages:
The sour density of the acidic ion liquid that 1, contains multi-sulfonic is high, and catalytic activity is good;
2, catalyzer usage quantity is few and to recycle middle loss amount also less;
3, not facile hydrolysis of catalyzer, it is prepared and working conditions is fairly simple, convenience;
4, catalyzer can biological degradation, environmental friendliness;
5, whole reaction process is simple, convenient, economical, is convenient to large-scale industrialization and produces.
Accompanying drawing explanation
Fig. 1 is that multi-sulfonic bronsted acid ionic-liquid catalyst of the present invention is synthetic 2,3,4,5,6,7-, six hydrogen-6,6-dimethyl-4-oxo-2, the product yield figure while recycling in 3-phenylbenzene-N-(phenylimino) indazole-1-thioamides.
Fig. 2 is that multi-sulfonic bronsted acid ionic-liquid catalyst of the present invention is at synthetic 3-(4-cyano-phenyl)-2,3,4,5,6,7-six hydrogen-6, the product yield figure while recycling in 6-dimethyl-4-oxo-2-phenyl-N-(phenylimino) indazole-1-thioamides.
Embodiment
Substantive features of the present invention and unusual effect can be embodied from following embodiment; but they do not impose any restrictions the present invention; those skilled in the art's content according to the present invention is made some nonessential improvement and adjustment, all belongs to protection scope of the present invention.Below by embodiment, the present invention is further illustrated, wherein in embodiment the test of reaction product to characterize what use be the nuclear magnetic resonance analyser that German Bruker company, model are AVANCE-II400MHz; The fusing point of reaction product adopts capillary tube technique to measure.
Embodiment 1: by 2mmol phenyl aldehyde, 2mmol dithizone, 2mmol5,5-dimethyl-hydroresorcinol and 0.6mmol BAIL join in the 25ml single port bottle with stirrer and prolong.Under 80 ℃ of vigorous stirring, react 35min, TLC (thin plate chromatography) follows the tracks of and detects (developping agent is normal hexane: ethyl acetate=4:1), and raw material point disappears, frozen water is cooling, suction filtration, and filter residue separates and obtains pure 2 through silica gel chromatographic column (moving phase is normal hexane: ethyl acetate=4:1), 3,4,5,6,7-six hydrogen-6,6-dimethyl-4-oxo-2,3-phenylbenzene-N-(phenylimino) indazole-1-thioamides, yield is 85%.Filtrate (main component is BAIL and water) is reusable after rotary evaporation, vacuum-drying first.
2,3,4,5,6,7-, six hydrogen-6,6-dimethyl-4-oxo-2,3-phenylbenzene-N-(phenylimino) indazole-1-thioamides: m.p.186～188 ℃;
1h NMR (400MHz, CDCl3): δ=0.78 (s, 3H), 0.96 (s, 3H), 1.94 (m, J=17.5Hz, 2H), 2.19 (m, J=16.2Hz, 2H), 5.30 (s, 1H), 7.11 (t, J=7.3Hz, 1H), 7.20～7.27 (m, 6H), 7.51 (dd
1j=8.2Hz,
2j=1.3Hz, 2H), 7.52～7.59 (m, 6H)
Embodiment 2: by 2mmol 4-chloro-benzaldehyde, 2mmol dithizone, 2mmol5,5-dimethyl-hydroresorcinol and 0.7mmol BAIL join in the 25ml single port bottle with stirrer and prolong.Under 90 ℃ of vigorous stirring, react 40min, TLC (thin plate chromatography) follows the tracks of and detects (developping agent is normal hexane: ethyl acetate=4:1), raw material point disappears, frozen water is cooling, suction filtration, filter residue separates and obtains pure 3-(4-chloro phenyl)-2 through silica gel chromatographic column (moving phase is normal hexane: ethyl acetate=4:1), 3,4,5,6,7-, six hydrogen-6,6-dimethyl-4-oxo-2-phenyl-N-(phenylimino) indazole-1-thioamides, yield is 82%.Filtrate (main component is BAIL and water) is reusable after rotary evaporation, vacuum-drying first.
3-(4-chloro phenyl)-2,3,4,5,6,7-six hydrogen-6,6-dimethyl-4-oxo-2-phenyl-N-(phenylimino) indazole-1-thioamides: m.p.87～89 ℃;
1h NMR (400MHz, CDCl
3): δ=0.80 (s, 3H), 0.95 (s, 3H), 1.96 (m, J=17.5Hz, 2H), 2.17 (m, J=16.1Hz, 2H), 5.26 (s, 1H), 7.21～7.24 (m, 5H), 7.32 (d, J=8.5Hz, 4H), 7.54～7.58 (m, 5H)
Embodiment 3: to phenyl phenyl aldehyde, 2mmol dithizone, 2mmol5,5-dimethyl-hydroresorcinol and 0.6mmol BAIL join in the 25ml single port bottle with stirrer and prolong by 2mmol.Under 95 ℃ of vigorous stirring, react 40min, TLC (thin plate chromatography) follows the tracks of and detects (developping agent is normal hexane: ethyl acetate=4:1), raw material point disappears, frozen water is cooling, suction filtration, filter residue separates and obtains pure 3-(4-phenylbenzene)-2 through silica gel chromatographic column (moving phase is normal hexane: ethyl acetate=4:1), 3,4,5,6,7-, six hydrogen-6,6-dimethyl-4-oxo-2-phenyl-N-(phenylimino) indazole-1-thioamides, yield is 81%.Filtrate (main component is BAIL and water) is reusable after rotary evaporation, vacuum-drying first.
3-(4-phenylbenzene)-2,3,4,5,6,7-six hydrogen-6,6-dimethyl-4-oxo-2-phenyl-N-(phenylimino) indazole-1-thioamides: m.p.179～181 ℃;
1h NMR (400MHz, CDCl
3): δ=0.84 (s, 3H), 0.94 (s, 3H), 1.92 (m, J=16.5Hz, 2H), 2.14 (m, J=16.5Hz, 2H), 5.46 (s, 1H), 7.19 (dd,
1j=8.1Hz,
2j=2.1Hz, 2H), 7.21～7.26 (m, 5H), 7.49～7.59 (m, 8H), 7.66 (d, J=8.5Hz, 4H)
Embodiment 4: by 2mmol p-tolyl aldehyde, 2mmol dithizone, 2mmol5,5-dimethyl-hydroresorcinol and 1.0mmol BAIL join in the 25ml single port bottle with stirrer and prolong.Under 100 ℃ of vigorous stirring, react 50min, TLC (thin plate chromatography) follows the tracks of and detects (developping agent is normal hexane: ethyl acetate=4:1), and raw material point disappears, frozen water is cooling, suction filtration, filter residue separates and obtains pure 2,3 through silica gel chromatographic column (moving phase is normal hexane: ethyl acetate=4:1), 4,5,6,7-, six hydrogen-6,6-dimethyl-4-oxo-2-phenyl-N-(phenylimino)-3-p-methylphenyl indazole-1-thioamides, yield is 84%.Filtrate (main component is BAIL and water) is reusable after rotary evaporation, vacuum-drying first.
2,3,4,5,6,7-, six hydrogen-6,6-dimethyl-4-oxo-2-phenyl-N-(phenylimino)-3-p-methylphenyl indazole-1-thioamides: m.p.79～81 ℃;
1h NMR (400MHz, CDCl
3): δ=0.82 (s, 3H), 0.95 (s, 3H), 1.96 (m, J=17.2Hz, 2H), 2.16 (m, J=16.5Hz, 2H), 2.60 (s, 3H), 5.27 (s, 1H), 7.08 (d, J=7.9Hz, 2H), 7.22～7.24 (m, 5H), 7.33 (d, J=8.1Hz, 2H), 7.53～7.60 (m, 5H)
Embodiment 5: to cyanobenzaldehyde, 2mmol dithizone, 2mmol5,5-dimethyl-hydroresorcinol and 0.6mmol BAIL join in the 25ml single port bottle with stirrer and prolong by 2mmol.Under 80 ℃ of vigorous stirring, react 35min, TLC (thin plate chromatography) follows the tracks of and detects (developping agent is normal hexane: ethyl acetate=4:1), raw material point disappears, frozen water is cooling, suction filtration, filter residue separates and obtains pure 3-(4-cyano-phenyl)-2 through silica gel chromatographic column (moving phase is normal hexane: ethyl acetate=4:1), 3,4,5,6,7-, six hydrogen-6,6-dimethyl-4-oxo-2-phenyl-N-(phenylimino) indazole-1-thioamides, yield is 87%.Filtrate (main component is BAIL and water) is reusable after rotary evaporation, vacuum-drying first.
3-(4-cyano-phenyl)-2,3,4,5,6,7-six hydrogen-6,6-dimethyl-4-oxo-2-phenyl-N-(phenylimino) indazole-1-thioamides: m.p.82～84 ℃;
1h NMR (400MHz, CDCl
3): δ=0.82 (s, 3H), 0.93 (s, 3H), 1.96 (m, J=17.3Hz, 2H), 2.12 (m, J=16.2Hz, 2H), 5.41 (s, 1H), 7.19 (dd,
1j=5.1Hz,
2j=2.2Hz, 2H), 7.20～7.25 (m, 5H), 7.52～7.58 (m, 5H) 7.60 (d, J=8.2Hz, 2H)
Embodiment 6: take embodiment 1 as probe reaction, make the active replica test of catalysts BAIL, ionic liquid is reused 5 times.Product 2,3,4,5,6,7-six hydrogen-6,6-dimethyl-4-oxo-2, the yield of 3-phenylbenzene-N-(phenylimino) indazole-1-thioamides changes sees Fig. 1.
Embodiment 7: take embodiment 5 as probe reaction, make the active replica test of catalysts BAIL, ionic liquid is reused 5 times.Product 3-(4-cyano-phenyl)-2,3,4,5,6,7-six hydrogen-6, the yield of 6-dimethyl-4-oxo-2-phenyl-N-(phenylimino) indazole-1-thioamides is shown in Fig. 2.
Can be found out by Fig. 1,2: catalyst B AIL is recycling synthetic 2,3,4,5,6,7-, six hydrogen-6,6-dimethyl-4-oxo-2,3-phenylbenzene-N-(phenylimino) indazole-1-thioamides and 3-(4-cyano-phenyl)-2,3,4,5,6,7-, six hydrogen-6, yield in the process of 6-dimethyl-4-oxo-2-phenyl-N-(phenylimino) indazole-1-thioamides is in a slight decrease, but reduction amplitude is all smaller.By showing above, catalyst B AIL can be recycled catalyzing and synthesizing in N-(phenylimino) indazole-1-thioamide analog compound.
Claims (3)
1. the method for synthetic N-(phenylimino) indazole-1-thioamide analog compound of green catalysis, it is characterized in that, aromatic aldehyde in described building-up reactions, dithizone and 5, 5-dimethyl-1, the mol ratio of hydroresorcinol is 1:1:1, the molar weight of multi-sulfonic bronsted acid ionic-liquid catalyst is 20～50% of aromatic aldehyde used, temperature of reaction is 80～100 ℃, reaction times is 25～60min, reaction pressure is a normal atmosphere, after reaction, frozen water is cooling, suction filtration, filter residue separates and obtains pure N-(phenylimino) indazole-1-thioamide analog compound through silica gel chromatographic column,
The structural formula of described multi-sulfonic bronsted acid ionic-liquid catalyst is:
2. the method for synthetic N-(phenylimino) indazole-1-thioamide analog compound of a kind of green catalysis as claimed in claim 1, it is characterized in that, described aromatic aldehyde is phenyl aldehyde, 4-chloro-benzaldehyde, o-chlorobenzaldehyde, m chlorobenzaldehyde, to phenyl phenyl aldehyde, p-tolyl aldehyde, aubepine, o-tolualdehyde, salicylaldhyde, p-Hydroxybenzaldehyde and to any in cyanobenzaldehyde.
3. the method for synthetic N-(phenylimino) indazole-1-thioamide analog compound of a kind of green catalysis as claimed in claim 1, is characterized in that, the filtrate after described suction filtration is reusable after rotary evaporation, vacuum-drying.
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