CN107011368A - A kind of preparation method of the hydroxyl phenyl boric acid of 3 methoxyl group 2 - Google Patents
A kind of preparation method of the hydroxyl phenyl boric acid of 3 methoxyl group 2 Download PDFInfo
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- CN107011368A CN107011368A CN201610748553.4A CN201610748553A CN107011368A CN 107011368 A CN107011368 A CN 107011368A CN 201610748553 A CN201610748553 A CN 201610748553A CN 107011368 A CN107011368 A CN 107011368A
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- phenyl boric
- preparation
- hydroxyl phenyl
- crude product
- white solid
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic System
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
Abstract
The present invention relates to a kind of preparation method of the hydroxyl phenyl boric acid of 3 methoxyl group 2, deprotection three-step reaction is mainly protected, introduces boronate and hydrolyzed by etherified hydroxy groups and obtains the hydroxyl phenyl boric acid of 3 methoxyl group of final product 2.At home and abroad in document, there is not been reported for the synthesis pertinent literature of the product；The synthetic method of product is simple, easy to operate, and yield is higher, and theoretical and experimental basis is provided for the synthesis of this class product.
Description
Technical field
The present invention relates to organic synthesis intermediate, more particularly to a kind of preparation side of 3- methoxyl groups -2- hydroxyl phenyl boric acids
Method.
Background technology
3- methoxyl group -2- hydroxyl phenyl boric acids are a kind of new aryl boric acid class compounds.Aryl boric acid is with Dan Fang
The boronic acid compounds of ring or many aromatic rings, are important organic synthesis intermediates, are not widely used in the synthesis of medicine with modification and not
The synthesis of asymmetric catalyst, isolate and purify in saccharide sensor device, material, also have in terms of controlled drug delivery system it is very important should
With.Application in recent years in the field such as liquid crystal display material and agricultural chemicals is also more and more extensive.Therefore, develop efficient, inexpensive, green
3- methoxyl group -2- hydroxyl phenyl boric acid the synthesis techniques that colour circle is protected, can be applied to industrialization, of far-reaching significance.
The content of the invention
Protected by etherified hydroxy groups, introduce boronate and hydrolysis deprotection three-step reaction obtain final product 3- methoxyl groups-
2- hydroxyl phenyl boric acids.
A kind of preparation method of 3- methoxyl groups -2- hydroxyl phenyl boric acids, comprises the following steps：
(1) etherified hydroxy groups is protected
With dichloromethane (CH2Cl2) it is solvent, 2- metoxyphenols (A) and DIPEA (DIEA) is mixed
After conjunction, under cryogenic, chloromethyl methyl ether (MOMCl) is slowly added dropwise, 6-8h is stirred at room temperature and obtains crude product B.
(2) boronate is introduced
Crude product B is dissolved in after a certain amount of methyl tertiary butyl ether(MTBE) (MTBE) with tetramethylethylenediamine (TMEDA), at -10 DEG C
It is slowly added to add a certain amount of triisopropyl borate (B (OiPr) after tert-butyl lithium, stirring and dissolving3), it is warming up to room temperature
It is stirred for 2-4h.Crude product is washed in two times using aqueous ammonium chloride solution, and separation merges organic layer, through dense after organic layer drying
Contracting, filtering and n-hexane wash to obtain white solid C.
(3) hydrolysis deprotection
White solid C is dissolved in HCl and THF in the mixed solvent (v/v=1:1) 1h, is stirred at room temperature, and revolving removes molten
Agent, then through filtering, washing, be dried to obtain white solid D.
Wherein, in step (1), the consumption of 2- metoxyphenols, DIPEA and chloromethyl methyl ether, according to matter
Amount ratio is calculated as 1:1~2:0.5~1；2- metoxyphenol quality (g) is with methylene chloride volume (mL) than being 1:5~15；It is described
Low temperature be 0~10 DEG C.
In step (2), crude product B, tetramethylethylenediamine, tert-butyl lithium, triisopropyl borate consumption, according to mass ratio
It is calculated as 1：0.5~2：0.5~1：1.5~3；Crude product B mass (g) and methyl tertiary butyl ether(MTBE), aqueous ammonium chloride solution, n-hexane three
The volume (mL) of person is than being 1：2~6：2~6：2~4；The concentration of aqueous ammonium chloride solution is 100~200g/L.
In step (3), white solid C mass and HCl, THF mixed solvent volume ratio are 1：3~9；HCl's is mole dense
Spend for 2~5mol/L.
Beneficial effects of the present invention：
(1) a kind of aryl boric acid class compound 3- methoxyl group -2- hydroxyl phenyl boric acids of research synthesis, current synthetic method is not yet
See document report；
(2) synthesis route is short, simple and easy to apply, environmental protection, and theoretical and experimental basis is provided for industrialized production；
(3) the 3- methoxyl group -2- hydroxyl phenyl boric acids purity of method synthesis is high, and yield is high, reduces production cost.
Brief description of the drawings
Fig. 1 is nuclear-magnetism result and intermediate；
Fig. 2 is 3- methoxyl group -2- hydroxyl phenyl boric acid collection of illustrative plates；
Fig. 3 is liquid chromatogram.
Embodiment
Embodiment 1
A kind of preparation method of 3- methoxyl groups -2- hydroxyl phenyl boric acids, comprises the following steps：
(1) etherified hydroxy groups is protected
4g 2- metoxyphenols (A) are dissolved in 35mL dichloromethane (CH2Cl2) in, 6g N, N- diisopropyls are added under ice bath
Base ethamine (DIEA), is cooled to after 5 DEG C, and 3.2g chloromethyl methyl ethers (MOMCl) are slowly added dropwise into mixture, stir at room temperature
6h, obtains crude product B.
(2) boronate is introduced
Crude product B 6g and tetramethylethylenediamine (TMEDA) 6g in step (1) is dissolved in 20mL methyl tertiary butyl ether(MTBE)s
(MTBE) in；Tert-butyl lithium 3g (3h) is slowly added at -10 DEG C, and is stirred after 3h, 9g triisopropyl borates (B is slowly added to
(OiPr)3) (2h), it is warming up to room temperature and is stirred for 3h.Then, 10mL aqueous ammonium chloride solutions are added, organic layer is separated, is used in combination
Merge organic layer after the washing of 10mL aqueous ammonium chloride solutions.Organic layer is concentrated into 5mL after drying, filtering, n-hexane 18ml washings are pure
Change to obtain white solid C 3.4g, yield 62%.
(3) hydrolysis deprotection
In HCl the and 10mL THF that 3g white solids C is dissolved in 10mL concentration 3mol/L, 1h is stirred at room temperature；Revolving is removed
THF is removed, then through filtering, washing, being dried to obtain 1.7g white solid D, yield 72%.
Embodiment 2
A kind of preparation method of 3- methoxyl groups -2- hydroxyl phenyl boric acids, comprises the following steps：
(1) etherified hydroxy groups is protected
4g 2- metoxyphenols (A) are dissolved in 20mL dichloromethane (CH2Cl2) in, 4g N, N- diisopropyls are added under ice bath
Base ethamine (DIEA), is cooled to after 5 DEG C, and 2g chloromethyl methyl ethers (MOMCl) are slowly added dropwise into mixture, 7h is stirred at room temperature,
Obtain crude product B.
(2) boronate is introduced
Crude product 6g and tetramethylethylenediamine (TMEDA) 9g in step (1) is dissolved in 36mL methyl tertiary butyl ether(MTBE)s (MTBE)
In；Tert-butyl lithium 12g (3h) is slowly added at -10 DEG C, and is stirred after 3h, 18g triisopropyl borates (B is slowly added to
(OiPr)3) (2h), it is warming up to room temperature and is stirred for 4h.Then, 18 mL aqueous ammonium chloride solutions (concentration is 200g/L), separation are added
Organic layer, and merge organic layer after being washed with 18mL aqueous ammonium chloride solutions.Organic layer is concentrated into 5mL, filtering, n-hexane after drying
24ml washings purify to obtain white solid C 4.4g, yield 80%.
(3) hydrolysis deprotection
White solid C 4g are dissolved in the HCl and 18mLTHF that 18mL concentration is 3mol/L, 1h is stirred at room temperature；Revolving
THF is removed, then through filtering, washing, being dried to obtain 2.33g white solid D, yield 74%.
Embodiment 3
A kind of preparation method of 3- methoxyl groups -2- hydroxyl phenyl boric acids, comprises the following steps：
(1) etherified hydroxy groups is protected
4g 2- metoxyphenols (A) are dissolved in 60mL dichloromethane (CH2Cl2) in, 8g N, N- diisopropyls are added under ice bath
Base ethamine (DIEA), is cooled to after 5 DEG C, and 4g chloromethyl methyl ethers (MOMCl) are slowly added dropwise into mixture, 8h is stirred at room temperature,
Obtain crude product B.
(2) boronate is introduced
Crude product B 6g and tetramethylethylenediamine (TMEDA) 12g in step (1) is dissolved in 12mL methyl tertiary butyl ether(MTBE)s
(MTBE) in；Tert-butyl lithium 10g (3h) is slowly added at -10 DEG C, and is stirred after 3h, 12g triisopropyl borates are slowly added to
(B(OiPr)3) (2h), it is warming up to room temperature and is stirred for 3h.Then, 6mL aqueous ammonium chloride solutions (concentration 100g/L) are added, separation has
Machine layer, and merge organic layer after being washed with 6mL aqueous ammonium chloride solutions.Organic layer is concentrated into 5mL, filtering, n-hexane after drying
12ml washings purify to obtain white solid C 2.9g, yield 53%.
(3) hydrolysis deprotection
White solid C 2.9g are dissolved in HCl the and 3ml THF that 3mL concentration is 3mol/L, 1h is stirred at room temperature；Revolving
THF is removed, then through filtering, washing, being dried to obtain 1.2g white solid D, yield 52%.
Claims (4)
1. a kind of preparation method of 3- methoxyl groups -2- hydroxyl phenyl boric acids, it is characterised in that comprise the following steps：
(1) etherified hydroxy groups is protected
With dichloromethane (CH2Cl2) it is solvent, after 2- metoxyphenols (A) and DIPEA (DIEA) are mixed,
Under cryogenic, chloromethyl methyl ether (MOMCl) is slowly added dropwise, 6-8h is stirred at room temperature and obtains crude product B.
(2) boronate is introduced
Crude product B is dissolved in after a certain amount of methyl tertiary butyl ether(MTBE) (MTBE) with tetramethylethylenediamine (TMEDA), slow at -10 DEG C
A certain amount of triisopropyl borate (B (OiPr) is added after adding tert-butyl lithium, stirring and dissolving3), it is warming up to room temperature and stirs again
Mix 2-4h.Crude product is washed in two times using aqueous ammonium chloride solution, and separation merges organic layer, through concentration, mistake after organic layer drying
Filter and n-hexane wash to obtain white solid C.
(3) hydrolysis deprotection
White solid C is dissolved in HCl and THF in the mixed solvent (v/v=1:1) 1h, is stirred at room temperature, and revolving removes solvent,
Again through filtering, washing, be dried to obtain white solid D.
2. a kind of preparation method of 3- methoxyl groups -2- hydroxyl phenyl boric acids according to claim 1, it is characterised in that step
(1) in, the consumption of 2- metoxyphenols, DIPEA and chloromethyl methyl ether is calculated as 1 according to mass ratio:1~2:
0.5~1；2- metoxyphenol quality (g) is with methylene chloride volume (mL) than being 1:5~15；Described low temperature is 0~10 DEG C.
3. a kind of preparation method of 3- methoxyl groups -2- hydroxyl phenyl boric acids according to claim 1, it is characterised in that step
(2) in, crude product B, tetramethylethylenediamine, tert-butyl lithium, triisopropyl borate consumption are calculated as 1 according to mass ratio：0.5~
2：0.5~1：1.5~3；Crude product B mass (g) and methyl tertiary butyl ether(MTBE), aqueous ammonium chloride solution, the volume of n-hexane three
(mL) than being 1：2~6：2~6：2~4；The concentration of aqueous ammonium chloride solution is 100~200g/L.
4. a kind of preparation method of 3- methoxyl groups -2- hydroxyl phenyl boric acids according to claim 1, it is characterised in that step
(3) in, white solid C mass and HCl, THF mixed solvent volume ratio are 1：3~9；HCl molar concentration is 2~5mol/
L。
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108409978A (en) * | 2018-02-28 | 2018-08-17 | 武汉大学 | A kind of metal-organic framework and preparation method thereof that can fast detect mercaptoamino acid |
Citations (2)
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|---|---|---|---|---|
| CN103804403A (en) * | 2014-02-24 | 2014-05-21 | 蚌埠中实化学技术有限公司 | Method for preparing 2-hydroxybenzeneboronic acid |
| CN103896974A (en) * | 2014-04-11 | 2014-07-02 | 北京乐威泰克医药技术有限公司 | Method for preparing 2-hydroxyphenylboronic acid |
-
2016
- 2016-08-29 CN CN201610748553.4A patent/CN107011368A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103804403A (en) * | 2014-02-24 | 2014-05-21 | 蚌埠中实化学技术有限公司 | Method for preparing 2-hydroxybenzeneboronic acid |
| CN103896974A (en) * | 2014-04-11 | 2014-07-02 | 北京乐威泰克医药技术有限公司 | Method for preparing 2-hydroxyphenylboronic acid |
Non-Patent Citations (1)
| Title |
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| JINGXIN LIU ET AL.: "Pd-Catalyzed C−S Activation for [3+3] Annulation of 2-(Methylthio)benzofuran-3-carboxylates and 2-Hydroxyphenylboronic Acids: Synthesis of Coumestan Derivatives", 《J. ORG. CHEM》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108409978A (en) * | 2018-02-28 | 2018-08-17 | 武汉大学 | A kind of metal-organic framework and preparation method thereof that can fast detect mercaptoamino acid |
| CN108409978B (en) * | 2018-02-28 | 2021-02-02 | 武汉大学 | Metal-organic framework capable of rapidly detecting mercapto-amino acid and preparation method thereof |
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