CN106748797B - A kind of preparation method of the naphthol derivative of 2 nitro 1 - Google Patents
A kind of preparation method of the naphthol derivative of 2 nitro 1 Download PDFInfo
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- CN106748797B CN106748797B CN201710065412.7A CN201710065412A CN106748797B CN 106748797 B CN106748797 B CN 106748797B CN 201710065412 A CN201710065412 A CN 201710065412A CN 106748797 B CN106748797 B CN 106748797B
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- C07C201/08—Preparation of nitro compounds by substitution of hydrogen atoms by nitro groups
Abstract
The invention belongs to organic synthesis field, and in particular to a kind of preparation method of the naphthol derivative of 2 nitro 1.1 naphthol derivative, nitrite tert-butyl and a certain amount of water of Formula II 1 are added into dry reactor, add a certain amount of organic solvent, a period of time is stirred under room temperature (referring generally to 20 25 DEG C), question response is into rear, reaction solution is filtered by filling the glass dropper of silica gel, ethyl acetate rinse filter cake, filtrate is spin-dried for, silica gel column chromatography separates, and obtains the target product of Formula II.Reaction equation can represent as follows：
Description
Technical field
The invention belongs to organic synthesis field, and in particular to a kind of preparation method of nitronaphthol derivative.
Background technology
Nitronaphthol is a kind of important organic synthesis intermediate and pharmaceutical intermediate.Synthesizing nitryl naphthols in the prior art
Classical way include the oxidation of nitrosonaphthol, the hydrolysis of the hydroxylating of nitronaphthalene, the nitrification of naphthols and chloro- 2 nitronaphthalenes of 1-
Deng.It is existing for the nitration reaction of naphthols prepares the method for nitronaphthol but these traditional methods have the shortcomings that many
There is nitrating agent used in technology to include natrium nitrosum, isoamyl nitrite, the halogen cyclohexadiene ketone of nitro four, ammonium ceric nitrate
Deng these methods generally produce o- and p- nitronaphthols, the mixture of more nitrophenols, cause target product purification difficult, yield
Lowly.Although ammonium ceric nitrate can selectively obtain o- nitronaphthols as nitrating agent, its is expensive, and reaction condition is severe
Carve.
As the application of nitronaphthol derivative in the prior art is more and more extensive, there is an urgent need to one kind warp by people
The defects of Ji, the convenient feasible method for preparing nitronaphthol derivative is to overcome art methods.
Prior art literature 1 and 2 is correspondingly disclosed a kind of nitration reaction research of phenol derivatives, these research into
Fruit shows that nitrite tert-butyl can be used as a kind of phenol derivatives nitrating agent well.
Prior art literature 1：Tertiary Butyl Nitrite Triggered Nitration of Phenols：
Solvent-and Structure-Dependent Kinetic Study, M.SATISHKUMAR etc.,《International
Journal of Chemical Kinetics》, 2016, DOI10.1002/kin.20979；
Prior art literature 2：Chemoselective Nitration of Phenols with tert-Butyl
Nitrite in Solution and on Solid Support, Dipankar Koley etc.,《ORGANIC LETTERS》,
2009, DOI10.1021/ol901731w.
But inventor but encounters when the nitration reaction that these reaction conditions are applied to naphthols prepares nitronaphthol
Difficulty, even being reacted under identical optimal conditions, the yield of the nitration reaction of naphthols is hovered 20% or so all the time, it is seen that
Due to the difference in reaction substrate structure, the above method disclosed in prior art literature 1-2 is also not suitable for preparing nitronaphthol
Derivative.Inventor is by research and probe repeatedly, it is proposed that a kind of to be tried at normal temperatures by nitrification of cheap nitrite tert-butyl
Agent, water are auxiliary agent, and reaction at normal temperatures can prepare the method suitable for industrialized production of nitronaphthol derivative in high yield.
The content of the invention
The defects of it is an object of the invention to overcome prior art, there is provided one kind prepares nitronaphthol by naphthol derivative and spread out
The method of biology, this method have the characteristics of production cost is low, process conditions are gentle, target product yield is high and purity is high, fit
In industrial production.
To realize the purpose of foregoing invention, the present invention is achieved through the following technical solutions：
The beta naphthal derivative of Formulas I -1 reacts under conditions of nitrite tert-butyl is nitrating agent, obtains shown in Formulas I
1- nitros-beta naphthal derivative (referring to formula one).
In above-mentioned Formulas I -1 and Formulas I, R1Represent one or more substituents on the phenyl ring that it is connected, each R1Independently of one another
Ground is selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 acyl group, halogen, C3-C6 cycloalkyl, C5-C14 virtue
The heteroaryl ,-NR of base, C5-C142R3。
Wherein, R2, R3It is independently from each other C1-C6 alkyl or hydrogen；The hetero atom of the heteroaryl is selected from O, S or N.
Above-mentioned alkyl, alkoxy, cycloalkyl, aryl and heteroaryl can be further substituted with a substituent, described
Substituent is selected from halogen or C1-C6 alkyl.
Specific preparation process is as follows：Beta naphthal derivative, the nitrite tert-butyl of Formulas I -1 are added into dry reactor
With a certain amount of water, a certain amount of organic solvent is added, a period of time is stirred under room temperature (referring generally to 20-25 DEG C), is treated anti-
Ying Chenghou, reaction solution is filtered by filling the glass dropper of silica gel, ethyl acetate rinse filter cake, filtrate is spin-dried for, silica gel column chromatography
Separation, obtains the target product of Formulas I.
Wherein, the beta naphthal derivative of Formulas I -1: nitrite tert-butyl: the mol ratio of water is 1: 1~3: 1~3；Preferably,
Beta naphthal derivative: nitrite tert-butyl: the mol ratio of water is 1: 2: 2.
Described organic solvent is any one in tetrahydrofuran, dioxane, ethyl acetate, dichloromethane or toluene
Or several mixture, it is preferable that the organic solvent is any one in tetrahydrofuran, dioxane, toluene.
The described reaction time is 1-12 hours, preferably 2-6 hours.
In order to realize the purpose of the present invention, another technical scheme of the invention is as follows：
The 1- naphthol derivatives of Formula II -1 react under conditions of nitrite tert-butyl is nitrating agent, obtain shown in Formula II
2- nitro -1- naphthol derivatives (referring to formula two).
In above-mentioned Formula II -1 and Formula II, R1Represent one or more substituents on the phenyl ring that it is connected, each R1It is only each other
On the spot selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 acyl group, halogen, C3-C6 cycloalkyl, C5-C14
The heteroaryl ,-NR of aryl, C5-C142R3。
Wherein, R2, R3It is independently from each other C1-C6 alkyl or hydrogen；The hetero atom of the heteroaryl is selected from O, S or N.
Above-mentioned alkyl, alkoxy, cycloalkyl, aryl and heteroaryl can be further substituted with a substituent, described
Substituent is selected from halogen or C1-C6 alkyl.
Specific preparation process is as follows：The tertiary fourth of 1- naphthol derivatives, nitrous acid of Formula II -1 is added into dry reactor
Ester and a certain amount of water, add a certain amount of organic solvent, and a period of time is stirred under room temperature (referring generally to 20-25 DEG C), is treated
React into rear, reaction solution is filtered by filling the glass dropper of silica gel, ethyl acetate rinse filter cake, filtrate is spin-dried for, silica gel column layer
Analysis separation, obtains the target product of Formula II.
Wherein, the 1- naphthol derivatives of Formula II -1: nitrite tert-butyl: the mol ratio of water is 1: 1~3: 1~3；It is preferred that
Ground, 1- naphthol derivatives: nitrite tert-butyl: the optimum molar ratio of water is 1: 2: 2.
Described organic solvent is appointing in tetrahydrofuran, dioxane, ethyl acetate, dichloromethane, acetonitrile or toluene
The mixture for one or more of anticipating, it is preferable that the organic solvent is any one in tetrahydrofuran, dioxane, toluene.
The described reaction time is 1-12 hours, preferably 2-6 hours.
In the present invention, unless otherwise instructed, described raw material I-1, II-1 and reagent can pass through commercially available acquisition.
The beneficial effects of the invention are as follows：A kind of new method of synthesizing nitryl naphthols is proposed, this method uses cheap nitre
Change reagent and reaction initiation material, react at normal temperatures and pressures, to obtain nitronaphthol derivative with purity in high yield；In addition,
The present invention is significantly improved the selectivity of reaction, is considerably improved the yield of target product using water as reaction promoter.
Embodiment
Below in conjunction with specific embodiment, further detailed description is carried out to the present invention.
Embodiment 1-16 reaction condition optimizations
With beta naphthal (formula 1a) for reaction raw materials, nitrite tert-butyl (formula 2a) is nitrating agent, explores various differences
Influence of the condition for reaction, select wherein representative embodiment 1-16, as a result as shown in Table 1：
Table one：
Reaction condition：1a (0.3mmol), 2a (2equiv), 2.5h is reacted under solvent (2mL) air conditionses；a1a(1mol)
for 12h.
Optimum reaction condition of the present invention is the reaction condition of embodiment 6 it can be seen from embodiment 1-16.In the reaction bar
Under part, reaction raw materials still can obtain 81% yield in the scale of 1mol levels, be suitable for industrialized production (embodiment 16).
The concrete operations of wherein embodiment 6 are as follows：Beta naphthal 43.2mg is added in dry schlenk bottles
(0.3mmol), nitrite tert-butyl 61.8mg (0.6mmol), water 10.8mg (0.6mmol), tetrahydrofuran (2mL), reaction bulb
2.5h is stirred at normal temperatures.After completion of the reaction, reaction solution is filtered by the glass dropper containing silica gel, after ethyl acetate rinse, filter
Liquid is spin-dried for, column chromatography for separation, obtains target product, yellow solid, yield 85%.1H NMR (300MHz, CDCl3)：12.19 (s,
1H), 8.88 (d, J=8.7Hz, 1H), 7.97 (d, J=9.0Hz, lH), 7.78 (d, J=7.8Hz, 1H), 7.70 (t, J=
7.8Hz, 1H), 7.48 (t, J=7.5Hz, 1H), 7.21 (d, J=9.0Hz, 1H)；13C NMR (75MHz, CDCl3)：158.9
139.3,131.0,129,4,128.7,126.9,125.7,123.2,119.4,119.3；IR (KBr, cm-1)：1542,1374；
LRMS (EI, 70eV) m/z (%)：189(M+, 100), 115 (77), 89 (39)
The synthesis of the bromo- 1- nitros-beta naphthals of the 6- of embodiment 17
The bromo- beta naphthal 66.6mg (0.3mmol) of 6-, nitrite tert-butyl are added in dry 10mL schlenk bottles
61.8mg (0.6mmol), water 10.8mg (0.6mmol), tetrahydrofuran (2mL), reaction bulb stirs 2.5h at normal temperatures.React
Bi Hou, reaction solution are filtered by the glass dropper containing silica gel, and after ethyl acetate rinse, filtrate is spin-dried for, and column chromatography for separation, obtains mesh
Mark product, yellow solid, yield 93%.1H NMR (300MHz, CDCl3)：12.13 (s, 1H), 8.77 (d, J=9.3Hz, 1H),
7.94-7.87 (m, 2H), 7.78-7.74 (m, 1H), 7.27 (t, J=9.0Hz, 1H)；13C NMR (75MHz, CDCl3)：
158.8,138.0,133.9,131.2 (2), 129.9,125.5,125.1,120.8,119.5；IR (KBr, cm-1)：1538,
1361；LRMS (EI, 70eV) m/z (%)：269 (M+2,21), 267 (M+, 22), 222 (100), 115 (97).
The synthesis of the 2- nitro -1- naphthols of embodiment 18
1- naphthols 43.2mg (0.3mmol), nitrite tert-butyl 61.8mg are added in dry 10mL schlenk bottles
(0.6mmol), water 10.8mg (0.6mmol), tetrahydrofuran (2mL), reaction bulb stirs 4h at normal temperatures.After completion of the reaction, instead
Liquid is answered to be filtered by the glass dropper containing silica gel, after ethyl acetate rinse, filtrate is spin-dried for, and column chromatography for separation, obtains target product,
Yellow solid, yield 82%.1H NMR (300MHz, CDCl3)：12.23 (s, 1H), 8.49 (d, J=8.1Hz, 1H), 7.98 (d,
J=9.6Hz, 1H), 7.80 (d, J=7.8Hz, 1H), 7.71 (t, J=7.5Hz, 1H), 7.61 (t, J=7.5Hz, 1H), 7.32
(d, J=9.3Hz, 1H)；13C NMR (75MHz, CDCl3)：155.7,138.7,137.4,131.4,127.9,127.1,
126.5,125.1,120.2,119.4；IR (KBr, cm-1)：1540,1370；LRMS (EI, 70eV) m/z (%)：189(M+,
100), 115 (74), 89 (34).
Embodiment described above is only the preferred embodiments of the present invention, and the simultaneously exhaustion of the feasible implementation of non-invention.For
For those skilled in the art, on the premise of without departing substantially from the principle of the invention and spirit, to any apparent made by it
Change, should all be contemplated as falling with the present invention claims within.
Claims (7)
1. the preparation method of the 2- nitro -1- naphthol derivatives shown in a kind of formula II, it is characterised in that the preparation method is anti-
Answer formula as follows：
In above-mentioned Formula II -1 and Formula II, R1Represent one or more substituents on the phenyl ring that it is connected, each R1Independently of one another
Selected from hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 acyl group, halogen, C3-C6 cycloalkyl, C5-C14 aryl,
C5-C14 heteroaryl ,-NR2R3；
Wherein, R2, R3It is independently from each other C1-C6 alkyl or hydrogen；The hetero atom of the heteroaryl is selected from O, S or N；
Above-mentioned alkyl, alkoxy, cycloalkyl, aryl and heteroaryl can be further substituted with a substituent, described substitution
Base is selected from halogen or C1-C6 alkyl；
The preparation method concrete operations are as follows：1- naphthol derivatives, the nitrous acid of Formula II -1 are added into dry reactor
The tert-butyl ester and a certain amount of water, add a certain amount of organic solvent, and a period of time is stirred at room temperature, and question response, will into rear
Reaction solution is filtered by filling the glass dropper of silica gel, and ethyl acetate rinse filter cake, filtrate is spin-dried for, and silica gel column chromatography separation, is obtained
The target product of Formula II.
2. the method as described in claim 1, it is characterised in that：The 1- naphthol derivatives of Formula II -1: nitrite tert-butyl: water
Mol ratio is 1: 1~3: 1~3.
3. according to the method for claim 2, it is characterised in that：1- naphthol derivatives: nitrite tert-butyl: the mol ratio of water
Preferably 1: 2: 2.
4. the method as described in claim 1, it is characterised in that：Described organic solvent is tetrahydrofuran, dioxane, acetic acid
Any one or a few mixture in ethyl ester, dichloromethane or toluene.
5. according to the method for claim 4, it is characterised in that the organic solvent is tetrahydrofuran, dioxane, toluene
In any one.
6. the method as described in claim 1, it is characterised in that the described reaction time is 1-12 hours.
7. according to the method for claim 6, it is characterised in that the described reaction time is 2-6 hours.
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| CN113717052B (en) * | 2021-08-26 | 2024-04-05 | 武汉朋和科技有限公司 | Production process of 2-nitro-1-naphthol |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1709856A (en) * | 2005-06-10 | 2005-12-21 | 中国科学院上海有机化学研究所 | Nitrofication method for catalysis of phenol and diphenyl ether compounds using metal salt |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1709856A (en) * | 2005-06-10 | 2005-12-21 | 中国科学院上海有机化学研究所 | Nitrofication method for catalysis of phenol and diphenyl ether compounds using metal salt |
Non-Patent Citations (2)
| Title |
|---|
| "Chemoselective Nitration of Phenols with tert-Butyl Nitrite in Solution and on Solid Support";Dipankar Koley et al.;《Org. Lett.》;20090821;第11卷(第18期);4172-4175 * |
| "Room-Temperature, Water-Promoted, Radical-Coupling Reactions of Phenols with tert-Butyl Nitrite";Wen-Ting Wei et al.;《Synlett》;20170621;第28卷;2153-2158 * |
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