CN104892540B - Simple preparation method of naphthoxazine ketone derivative - Google Patents
Simple preparation method of naphthoxazine ketone derivative Download PDFInfo
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- aromatic aldehyde
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- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- -1 naphthoxazine ketone Chemical class 0.000 title abstract description 14
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 33
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- 239000003054 catalyst Substances 0.000 claims abstract description 21
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000007787 solid Substances 0.000 claims abstract description 18
- 239000004202 carbamide Substances 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 15
- 150000003934 aromatic aldehydes Chemical class 0.000 claims abstract description 12
- 239000011831 acidic ionic liquid Substances 0.000 claims abstract description 10
- 238000005406 washing Methods 0.000 claims abstract description 9
- 238000001291 vacuum drying Methods 0.000 claims abstract description 8
- 235000013877 carbamide Nutrition 0.000 claims description 16
- 238000001914 filtration Methods 0.000 claims description 16
- GVQSEVRVQSAFNJ-UHFFFAOYSA-N benzo[f][1,2]benzoxazin-1-one Chemical class C1=CC=CC2=C3C(=O)C=NOC3=CC=C21 GVQSEVRVQSAFNJ-UHFFFAOYSA-N 0.000 claims description 15
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 9
- WMPDAIZRQDCGFH-UHFFFAOYSA-N 3-methoxybenzaldehyde Chemical compound COC1=CC=CC(C=O)=C1 WMPDAIZRQDCGFH-UHFFFAOYSA-N 0.000 claims description 8
- 239000000706 filtrate Substances 0.000 claims description 8
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 5
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 claims description 4
- SUISZCALMBHJQX-UHFFFAOYSA-N 3-bromobenzaldehyde Chemical compound BrC1=CC=CC(C=O)=C1 SUISZCALMBHJQX-UHFFFAOYSA-N 0.000 claims description 4
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 claims description 4
- FXLOVSHXALFLKQ-UHFFFAOYSA-N p-tolualdehyde Chemical compound CC1=CC=C(C=O)C=C1 FXLOVSHXALFLKQ-UHFFFAOYSA-N 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 claims description 2
- ZRYZBQLXDKPBDU-UHFFFAOYSA-N 4-bromobenzaldehyde Chemical compound BrC1=CC=C(C=O)C=C1 ZRYZBQLXDKPBDU-UHFFFAOYSA-N 0.000 claims 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims 1
- HUMNYLRZRPPJDN-KWCOIAHCSA-N benzaldehyde Chemical group O=[11CH]C1=CC=CC=C1 HUMNYLRZRPPJDN-KWCOIAHCSA-N 0.000 claims 1
- JWAZRIHNYRIHIV-UHFFFAOYSA-N 2-naphthol Chemical compound C1=CC=CC2=CC(O)=CC=C21 JWAZRIHNYRIHIV-UHFFFAOYSA-N 0.000 abstract description 33
- 229950011260 betanaphthol Drugs 0.000 abstract description 16
- 239000002608 ionic liquid Substances 0.000 abstract description 9
- 239000002994 raw material Substances 0.000 abstract description 9
- 238000010992 reflux Methods 0.000 abstract description 5
- 238000006555 catalytic reaction Methods 0.000 abstract description 4
- 238000005516 engineering process Methods 0.000 abstract description 2
- 230000003197 catalytic effect Effects 0.000 abstract 1
- 239000007810 chemical reaction solvent Substances 0.000 abstract 1
- 238000001816 cooling Methods 0.000 abstract 1
- 238000000967 suction filtration Methods 0.000 abstract 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 43
- 150000002500 ions Chemical class 0.000 description 22
- 239000007788 liquid Substances 0.000 description 22
- 230000002378 acidificating effect Effects 0.000 description 21
- 239000000047 product Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 238000004587 chromatography analysis Methods 0.000 description 6
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 5
- 238000011049 filling Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 238000012805 post-processing Methods 0.000 description 4
- 230000008569 process Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000010189 synthetic method Methods 0.000 description 3
- PKZJLOCLABXVMC-UHFFFAOYSA-N 2-Methoxybenzaldehyde Chemical compound COC1=CC=CC=C1C=O PKZJLOCLABXVMC-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 150000004904 1,3,5-trioxanes Chemical class 0.000 description 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000007848 Bronsted acid Substances 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 102000011759 adducin Human genes 0.000 description 1
- 108010076723 adducin Proteins 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000001820 anti-cytotoxin effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000010936 aqueous wash Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 230000007096 poisonous effect Effects 0.000 description 1
- KCXFHTAICRTXLI-UHFFFAOYSA-N propane-1-sulfonic acid Chemical compound CCCS(O)(=O)=O KCXFHTAICRTXLI-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
- C07D263/60—Naphthoxazoles; Hydrogenated naphthoxazoles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0277—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature
- B01J31/0278—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre
- B01J31/0285—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides comprising ionic liquids, as components in catalyst systems or catalysts per se, the ionic liquid compounds being used in the molten state at the respective reaction temperature containing nitrogen as cationic centre also containing elements or functional groups covered by B01J31/0201 - B01J31/0274
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention discloses a simple preparation method of a naphthoxazine ketone derivative and belongs to the field of an ionic liquid catalysis technology. In the preparation reaction, molar ratio of aromatic aldehyde to beta-naphthol to urea is 1:1:1; molar weight of an acidic ionic liquid catalyst is 5-10% of molar weight of aromatic aldehyde; volume (ml) of a reaction solvent 90% ethanol water is 4-6 times larger than molar weight (mmol) of aromatic aldehyde; reaction pressure is an atmospheric pressure; and reflux reaction lasts for 50-110 min. After the reaction is finished, preparation comprises steps as follows: cooling to room temperature until a lot of solids separate out, crushing the solids, standing, carrying out suction filtration, washing a filter residue with 90% ethanol water, and carrying out vacuum drying to obtain a product. In comparison with a preparation method by the use of other acidic ionic liquid catalyst, the method provided by the invention has characteristics as follows: catalytic activity of the catalyst is high; biodegradability is good; utilization rate of raw materials is high; reaction conditions are mild; and operations during the whole preparation process are simple and convenient. The method provided by the invention is convenient for industrial large-scale application.
Description
Technical field
The invention belongs to ionic liquid-catalyzed technical field is and in particular to a kind of simplicity prepares naphtho- oxazinone derivative
Method.
Background technology
Heterocyclic compound generally existing in nature, and closely bound up with the life of people, in the past few decades in
Cause the very big interest of people.And the naphtho- oxazinone derivative containing piperazine ketone construction unit is widely present in and has
In the natural product of biological activity, there is important pharmacology and biologic activity, antitumor, anti-inflammatory can be played, resist very
Bacterium and anticytotoxin etc. act on.Such compound is generally carried out by three component one pot reactions of betanaphthol, aldehyde and carbamide
Synthesis, but using traditional inorganic acid catalyst generally existing response time length, yield be not high enough, poisonous and harmful, post processing numerous
The shortcomings of trivial, environmental pollution is serious.Therefore, develop a kind of green, efficiently, conveniently and efficiently prepare naphtho- oxazinone derivative
Method becomes many organic synthesiss worker's questions of common concern.
Acidic ion liquid, particularly more stable to water and air bronsted acid ionic liquid, due to its tool
The features such as species is many, active site density height, uniform intensity distribution, active sites not easily run off are had to be applied to naphtho- piperazine ketone and spread out
In biological preparation process.Such as Fang Dong etc. employs the hydrogenation 1- propane sulfonic acid yl pyridines hydrochloric acid of the sulphuric acid containing a sulfonate radical
Property ionic liquid as catalyst, can effectively be catalyzed aromatic aldehyde in the absence of a solvent, betanaphthol and carbamide occur three
Component " one kettle way " reaction is prepared for a series of naphtho- oxazinone derivative, wherein acidic ionic liquid catalysts be evaporated off molten
Can recycle after agent (synthesis [p] of functionalized ion liquid solvent-free catalysis naphtho- oxazinone derivative, application number:
201210272622.0).
The structural matrix of the acidic ion liquid that said method is adopted is the pyridine structure of difficult for biological degradation, this be with green
The policy of color chemical industry is contrary.Additionally, the reaction of synthesis naphtho- oxazinone derivative, due to being inhomogeneous reaction, needs to heat
Could be efficiently against boundary resistance so that reaction can be smoothed out to more than 150 DEG C, reaction condition is harsher；
Again, acidic ionic liquid catalysts need solvent process is evaporated off before recycling, and process is complex and consumes energy higher,
Reaction dissolvent can not recycle, and wastes larger；Finally although using uninanned platform in above-mentioned synthetic method, but
In order to carry out separating product and imidazole radicals acidic ionic liquid catalysts in last handling process, employ relatively complicated
Add 95% ethanol to separate out product, washing etc. to separate and purification step, increased its difficulty in industrial applications.
Content of the invention
Derive it is an object of the invention to overcoming and preparing naphtho- piperazine ketone using presence of acidic ionic liquid catalyst in prior art
There is ionic liquid not easily biological-degradable, reaction temperature is higher during thing, the shortcomings of raw material availability is low, post processing is complicated,
And provide that a kind of easily biological-degradable, reaction condition are gentle, Atom economy is high, simply and easily acidic ion liquid is made for post processing
Green catalyst, 90% ethanol water makees the method that naphtho- oxazinone derivative is prepared in catalysis under solvent condition.
The structural formula of acidic ionic liquid catalysts used in the present invention is:
The method that a kind of simplicity provided by the present invention prepares naphtho- oxazinone derivative, its chemical equation is:
In wherein reacting, the mol ratio of aromatic aldehyde (i), betanaphthol (ii) and carbamide (iii) is 1:1:1, acidic ion liquid
The mole of catalyst is the 5～10% of aromatic aldehyde used, and volume in terms of milliliter for reaction dissolvent 90% ethanol water is
Aromatic aldehyde by mM in terms of 4～6 times of mole, reaction pressure is an atmospheric pressure, back flow reaction 50～110min, reaction
It is cooled to room temperature after end, have a large amount of solids to separate out, pulverize solid, standing, sucking filtration, gained filtering residue 90% ethanol aqueous wash
Wash, be vacuum dried after obtain pure naphtho- oxazinone derivative (iv).Filtrate any process need not be directly used in next secondary response, can
To reuse at least 5 times, its product yield is not obviously lowered.
Aromatic aldehyde used by the present invention be benzaldehyde, 4-chloro-benzaldehyde, o-chlorobenzaldehyde, p-tolyl aldehyde, to bromobenzene
Any one in formaldehyde, o-methoxybenzaldehyde, P-methoxybenzal-dehyde, 3-bromobenzaldehyde, m-methoxybenzaldehyde.
The synthetic method of acidic ionic liquid catalysts used in the present invention, with reference to associated materials (a convenient
Approach for the synthesis of 1,3,5-trioxanes under solvent-free conditions
At room temperature, monatshefte f ü r chemie chemical monthly, 2014,145 (6): 1017
～1022).
The present invention has the advantage that compared with making the synthetic method of catalyst with other acidic ion liquids
1st, two-so are contained3The acidity of the acidic ion liquid of h is high, and catalysis activity is high, and usage amount is less；
2nd, reaction raw materials utilization rate is high, and Atom economy is preferable；
3rd, reaction dissolvent can recycle, cost-effective, environmental protection；
4th, catalyst is readily biodegradable, friendly to human and environment；
5th, reaction condition is gentleer, energy-saving consumption-reducing；
6th, whole preparation process post processing is simple, is easy to industrialization large-scale production.
Specific embodiment
The substantive features of the present invention and remarkable result can emerge from from following embodiments, but they are not to this
Invention imposes any restrictions, and those skilled in the art makes some nonessential improvement according to present disclosure and adjusts, all
Belong to protection scope of the present invention.Below by specific embodiment, the present invention is further illustrated, wherein in embodiment
The test of product characterizes the nuclear magnetic resonance analyser of the model avance-ii 300mhz using German bruker company；
Examination of infrared spectrum characterizes the model bruker tensor 37 ft-ir infrared spectrum using German bruker company
Instrument, kbr tabletting；The fusing point of product adopts capillary tube method to measure.
Embodiment 1
1mmol benzaldehyde, 1mmol betanaphthol, 1mmol carbamide and 0.06mmol acidic ion liquid are added separately to
Fill in the 25ml single port bottle with stirrer and condensing tube of 4ml 90% ethanol water (volume ratio).Heating reflux reaction
52min, tlc (thin plate chromatography) detect, raw material point disappears, and is cooled to room temperature, have a large amount of solids to separate out, pulverize solid, and standing is taken out
Filter, obtains pure 1,2- dihydro -1- phenyl naphtho- [1,2-e] [1,3] after the washing of gained filtering residue 90% ethanol water, vacuum drying
Piperazine -3- ketone, yield is 88%.Reused after being directly added into benzaldehyde, betanaphthol and carbamide in filtrate.
1,2- dihydro -1- phenyl naphtho- [1,2-e] [1,3] piperazine -3- ketone: m.p.218～220 DEG C；Ir (kbr): 3294,
1728,1514cm-1；1H nmr (300mhz, dmso-d6): δ=6.17 (d, j=2.1hz, 1h), 7.22～8.01 (m, 11h),
8.85 (brs, 1h)
Embodiment 2
1mmol o-chlorobenzaldehyde, 1mmol betanaphthol, 1mmol carbamide and 0.06mmol acidic ion liquid are separately added into
To in the 25ml single port bottle with stirrer and condensing tube filling 6ml 90% ethanol water (volume ratio).It is heated to reflux anti-
Answer 73min, tlc (thin plate chromatography) detects, raw material point disappears, and is cooled to room temperature, have a large amount of solids to separate out, pulverize solid, standing,
Sucking filtration, gained filtering residue 90% ethanol water washing, vacuum drying after obtain pure 1,2- dihydro -1- (2- chlorphenyl) naphtho- [1,
2-e] [1,3] piperazine -3- ketone, yield is 85%.Repeated after being directly added into o-chlorobenzaldehyde, betanaphthol and carbamide in filtrate
Use.
1,2- dihydro -1- (2- chlorphenyl) naphtho- [1,2-e] [1,3] piperazine -3- ketone: m.p.250～252 DEG C；ir
(kbr): 3238,3122,1726,1394,1231cm-1；1H nmr (300mhz, dmso-d6): δ=6.48 (d, j=2.9hz,
1h), 7.16～8.03 (m, 10h), 8.86 (brs, 1h)
Embodiment 3
1mmol 3-bromobenzaldehyde, 1mmol betanaphthol, 1mmol carbamide and 0.07mmol acidic ion liquid are added respectively
Enter in the 25ml single port bottle with stirrer and condensing tube filling 6ml 90% ethanol water (volume ratio).It is heated to reflux
Reaction 82min, tlc (thin plate chromatography) detect, raw material point disappears, and is cooled to room temperature, have a large amount of solids to separate out, pulverize solid, quiet
Put, sucking filtration, after the washing of gained filtering residue 90% ethanol water, vacuum drying, obtain pure 1,2- dihydro -1- (3- bromophenyl) naphtho-
[1,2-e] [1,3] piperazine -3- ketone, yield is 83%.Carry out after being directly added into 3-bromobenzaldehyde, betanaphthol and carbamide in filtrate
Reuse.
1,2- dihydro -1- (3- bromophenyl) naphtho- [1,2-e] [1,3] piperazine -3- ketone: m.p.232～234 DEG C；ir
(kbr): 3265,3159,1744,1712,1221cm-1；1H nmr (300mhz, dmso-d6): δ=6.23 (d, j=2.9hz,
1h), 7.17～8.02 (m, 10h), 8.88 (brs, 1h)
Embodiment 4
1mmol m-methoxybenzaldehyde, 1mmol betanaphthol, 1mmol carbamide and 0.09mmol acidic ion liquid are divided
It is not added in the 25ml single port bottle with stirrer and condensing tube filling 5ml 90% ethanol water (volume ratio).Heating
Back flow reaction 96min, tlc (thin plate chromatography) detects, raw material point disappears, and is cooled to room temperature, has a large amount of solids to separate out, and pulverizes solid
Body, standing, sucking filtration, obtain pure 1,2- dihydro -1- (3- methoxyl group after the washing of gained filtering residue 90% ethanol water, vacuum drying
Phenyl) naphtho- [1,2-e] [1,3] piperazine -3- ketone, yield is 81%.It is directly added into m-methoxybenzaldehyde, betanaphthol in filtrate
Reused with after carbamide.
1,2- dihydro -1- (3- methoxyphenyl) naphtho- [1,2-e] [1,3] piperazine -3- ketone: m.p.202～204 DEG C；ir
(kbr): 3211,3134,1749,1599,1261cm-1；1H nmr (300mhz, dmso-d6): δ=6.15 (d, j=2.9hz,
1h), 6.73～7.94 (m, 10h), 8.86 (brs, 1h)
Embodiment 5
By 1mmol p-tolyl aldehyde, 1mmol betanaphthol, 1mmol carbamide and 0.10mmol acidic ion liquid respectively
It is added in the 25ml single port bottle with stirrer and condensing tube filling 5ml 90% ethanol water (volume ratio).Heat back
Stream reaction 89min, tlc (thin plate chromatography) detect, raw material point disappears, and is cooled to room temperature, have a large amount of solids to separate out, pulverize solid,
Standing, sucking filtration, obtain pure 1,2- dihydro -1- (4- aminomethyl phenyl) after the washing of gained filtering residue 90% ethanol water, vacuum drying
Naphtho- [1,2-e] [1,3] piperazine -3- ketone, yield is 82%.It is directly added into p-tolyl aldehyde, betanaphthol and carbamide in filtrate
After reused.
1,2- dihydro -1- (4- aminomethyl phenyl) naphtho- [1,2-e] [1,3] piperazine -3- ketone: m.p.166～168 DEG C；ir
(kbr): 3230,3135,1716cm-1；1H nmr (300mhz, dmso-d6): δ=2.23 (s, 3h), 6.14 (d, j=2.4hz,
1h), 7.12～7.98 (m, 10h), 8.82 (brs, 1h)
Embodiment 6
1mmol 4-chloro-benzaldehyde, 1mmol betanaphthol, 1mmol carbamide and 0.07mmol acidic ion liquid are added respectively
Enter in the 25ml single port bottle with stirrer and condensing tube filling 6ml 90% ethanol water (volume ratio).It is heated to reflux
Reaction 85min, tlc (thin plate chromatography) detect, raw material point disappears, and is cooled to room temperature, have a large amount of solids to separate out, pulverize solid, quiet
Put, sucking filtration, after the washing of gained filtering residue 90% ethanol water, vacuum drying, obtain pure 1,2- dihydro -1- (4- chlorphenyl) naphtho-
[1,2-e] [1,3] piperazine -3- ketone, yield is 87%.Carry out after being directly added into 4-chloro-benzaldehyde, betanaphthol and carbamide in filtrate
Reuse.
1,2- dihydro -1- (4- chlorphenyl) naphtho- [1,2-e] [1,3] piperazine -3- ketone: m.p.208～210 DEG C；ir
(kbr): 3221,3144,1736cm-1；1H nmr (300mhz, dmso-d6): δ=6.24 (s, 1h), 7.29～8.03 (m,
10h), 8.84 (brs, 1h)
Embodiment 7
With embodiment 1 as probe reaction, make the active replica test of catalysts acidic ion liquid, ionic liquid
Reuse 5 times, product 1, the yield change of 2- dihydro -1- phenyl naphtho- [1,2-e] [1,3] piperazine -3- ketone is shown in Table 1.
Embodiment 8
With embodiment 2 as probe reaction, make the active replica test of catalysts acidic ion liquid, ionic liquid
Reuse 5 times, product 1, the yield change of 2- dihydro -1- (2- chlorphenyl) naphtho- [1,2-e] [1,3] piperazine -3- ketone is shown in Table
2.
Embodiment 9
With embodiment 3 as probe reaction, make the active replica test of catalysts acidic ion liquid, ionic liquid
Reuse 5 times, product 1, the yield change of 2- dihydro -1- (3- bromophenyl) naphtho- [1,2-e] [1,3] piperazine -3- ketone is shown in Table
3.
The work in preparation 1,2- dihydro -1- phenyl naphtho- [1,2-e] [1,3] piperazine -3- ketone of table 1, acidic ion liquid
Property replica test result
| Acidic ion liquid access times | Yield (%) |
| 1 | 88 |
| 2 | 86 |
| 3 | 86 |
| 4 | 87 |
| 5 | 85 |
| 6 | 85 |
Table 2, acidic ion liquid are in preparation 1,2- dihydro -1- (2- chlorphenyl) naphtho- [1,2-e] [1,3] piperazine -3- ketone
In active replica test result
| Acidic ion liquid access times | Yield (%) |
| 1 | 85 |
| 2 | 83 |
| 3 | 84 |
| 4 | 86 |
| 5 | 83 |
| 6 | 84 |
Table 3, acidic ion liquid are in preparation 1,2- dihydro -1- (3- bromophenyl) naphtho- [1,2-e] [1,3] piperazine -3- ketone
In active replica test result
| Acidic ion liquid access times | Yield (%) |
| 1 | 83 |
| 2 | 81 |
| 3 | 82 |
| 4 | 83 |
| 5 | 81 |
| 6 | 81 |
By table 1,2,3 it can be seen that acidity of catalyst ionic liquid is recycling preparation 1,2- dihydro -1- phenyl naphtho-
[1,2-e] [1,3] piperazine -3- ketone, 1,2- dihydro -1- (2- chlorphenyl) naphtho- [1,2-e] [1,3] piperazine -3- ketone and 1,2- bis-
Yield during hydrogen -1- (3- bromophenyl) naphtho- [1,2-e] [1,3] piperazine -3- ketone is in a slight decrease, but reduction amplitude all than
Less.Therefore, this acidity of catalyst ionic liquid can be recycled during preparing naphtho- oxazinone derivative, and it is urged
Change activity not obviously lowered.
Claims (2)
1. a kind of simplicity prepare naphtho- oxazinone derivative method it is characterised in that described preparation reaction in aromatic aldehyde, β-naphthalene
The mol ratio of phenol and carbamide is 1:1:1, and the mole of acidic ionic liquid catalysts is the 5～10% of aromatic aldehyde used, reaction
The volume that solvent 90% ethanol water is counted with milliliter for aromatic aldehyde by mM in terms of 4～6 times of mole, reaction pressure
For an atmospheric pressure, back flow reaction 50～110min, reaction is cooled to room temperature after terminating, and has a large amount of solids to separate out, pulverizes solid,
Standing, sucking filtration, obtain naphtho- oxazinone derivative after the washing of gained filtering residue 90% ethanol water, vacuum drying；
Described aromatic aldehyde is benzaldehyde, 4-chloro-benzaldehyde, o-chlorobenzaldehyde, p-tolyl aldehyde, p-bromobenzaldehyde, O-methoxy
Any one in benzaldehyde, P-methoxybenzal-dehyde, 3-bromobenzaldehyde, m-methoxybenzaldehyde；
The structural formula of described acidic ionic liquid catalysts is:
2. a kind of simplicity prepares the method for naphtho- oxazinone derivative it is characterised in that described sucking filtration as claimed in claim 1
Filtrate afterwards need not any be processed reusable at least 5 times.
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