CN110330417A - The preparation method of 2,5- 4-dihydroxy benzaldehyde - Google Patents
The preparation method of 2,5- 4-dihydroxy benzaldehyde Download PDFInfo
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- CN110330417A CN110330417A CN201910761047.2A CN201910761047A CN110330417A CN 110330417 A CN110330417 A CN 110330417A CN 201910761047 A CN201910761047 A CN 201910761047A CN 110330417 A CN110330417 A CN 110330417A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/22—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogens; by substitution of halogen atoms by other halogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/455—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation with carboxylic acids or their derivatives
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
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Abstract
The present invention provides a kind of method for synthesizing 2,5- 4-dihydroxy benzaldehyde.This method obtains 2,5- 4-dihydroxy benzaldehyde using terephthaldehyde's ether as raw material, through bromination reaction, grignard reaction (Grignard reaction), demethylating reaction.Preparation condition of the present invention is mild, simple process, and has stronger industrial application value.
Description
Technical field
The present invention relates to a kind of preparation sides of important intermediate 2,5- 4-dihydroxy benzaldehyde for being used to prepare liquid-crystal compounds
Method.
Background technique
2,5- 4-dihydroxy benzaldehydes are a kind of important intermediates, have extensive use in terms of high molecule liquid crystal, dyestuff.
The synthetic route for preparing 2,5- 4-dihydroxy benzaldehyde at present does not have specific document report.Therefore, one is also lacked at present
Kind preparation process is simple, at low cost, is suitble to the preparation method of 2, the 5- 4-dihydroxy benzaldehyde of industrialization amplification.
Summary of the invention
Easy to operate the purpose of the present invention is to provide a kind of mild condition, yield is higher and with before industrial applications
The preparation method of the 2,5- 4-dihydroxy benzaldehyde of scape.
The preparation method of 2,5- 4-dihydroxy benzaldehyde of the invention, comprising the following steps:
First step bromination reaction: using terephthaldehyde's ether as raw material, using n,N-Dimethylformamide as solvent, with N- bromo fourth
Imidodicarbonic diamide (NBS) is bromide reagent, is reacted 3~5 hours, and reaction solution extracts through washing, layering, halogenated alkane, solvent is evaporated off,
Obtain liquid 2, the molar ratio of 5- dimethoxy bromobenzene, n,N-Dimethylformamide used and terephthaldehyde's ether is 10~15:1；
The molar ratio of N- bromo-succinimide used and terephthaldehyde's ether is 0.8~1:1；
Second step grignard reaction (Grignard reaction):, will be obtained by the first step with tetrahydrofuran (THF) for solvent
2,5- dimethoxy bromobenzenes are reacted with magnesium powder, and product reacts 1~2 hour with n,N-Dimethylformamide (DMF) again, reaction solution
It is hydrolyzed, adjusts reaction solution pH=3, halogenated alkane, which is extracted, is layered, saturated salt is washed, solvent is evaporated off obtains 2,5- dimethoxy benzene
Formaldehyde, 1.1~1.5:1 of molar ratio of magnesium powder used and 2,5- dimethoxy bromobenzene；N,N-dimethylformamide and 2,5- used
2~2.2:1 of molar ratio of dimethoxy bromobenzene；
Third step demethylating reaction:, using halogenated alkane as solvent, by 2,5- dimethoxy benzaldehyde obtained by second step and nothing
2,5- 4-dihydroxy benzaldehyde, halogenated alkane used and 2,5- dimethoxy are obtained through demethylating reaction under the action of water alchlor
The weight ratio of benzaldehyde is 7~10:1, and the molar ratio of aluminum trichloride (anhydrous) used and 2,5- dimethoxy benzaldehyde is 2~2.2:
1
Specific synthetic route is as follows:
The present invention is using terephthaldehyde's ether as raw material, through bromination reaction, grignard reaction (Grignard reaction), piptonychia
Base reacts to obtain 2,5- 4-dihydroxy benzaldehyde.Preparation condition of the present invention is mild, simple process, and has stronger industrial applications
Value.
Specific embodiment
The present invention is further illustrated with reference to embodiments.
Embodiment 1
1) synthesis of 2,5- dimethoxy bromobenzene
38.5g (278.6mmol) terephthaldehyde ether, 120g N, N- dimethyl formyl are sequentially added into 500ml four-hole bottle
Amine (DMF), mechanical stirring is cooled to 10 DEG C and 45g (252.8mmol) N- bromo succinyl is slowly added dropwise to being completely dissolved at room temperature
Imines and the prepared solution of n,N-Dimethylformamide, drip off for 1 hour or so, reaction 1 hour, at room temperature slowly to reaction solution
200ml water is added, dichloroethanes (100mL) is added and extracts 2 times, organic layer is extracted with saturated brine (100mL), organic layer nothing
Aqueous sodium persulfate is dried overnight, and is filtered, and filtrate steaming removal solvent obtains brown color liquid 2,5- dimethoxy bromobenzene 49.3g.
2) synthesis of 2,5- dimethoxy benzaldehyde
7.5g (312.5mmol) magnesium powder, 35g tetrahydrofuran (THF), nitrogen protection, machinery are added into 500mL four-hole bottle
The drop of solution 10 that lower dropwise addition 50g (230.3mmol) the 2,5- dimethoxy bromobenzene of stirring and tetrahydrofuran (THF) are prepared causes instead
It answers, then maintains the reflux for continuing to be added dropwise, be dripped off in 3 hours.It flows back again 0.5 hour.Anti- liquid is cooled to 10 DEG C hereinafter, 35g is added dropwise
(479.5mmol) n,N-Dimethylformamide is stirred to react 1 hour.It is slowly added into 100g water at 30 DEG C of control, uses salt at room temperature
The extraction of 80mL dichloroethanes is added in acid for adjusting pH=3, and organic layer is extracted with saturated brine, is layered, rotates to obtain brown liquid 2,5-
Dimethoxy benzaldehyde 34.4g.
3) synthesis of 2,5- 4-dihydroxy benzaldehyde
Addition 43.5g (261.7mmol) 2,5- dimethoxy benzaldehyde into 500mL four-hole bottle, 200mL dichloroethanes,
69.7g (523.4mmol) aluminum trichloride (anhydrous) is added under mechanical stirring in nitrogen protection by several times, reacts 3 hours for 65 DEG C after adding,
Cooling down is slowly added into 125mL water to 10 DEG C, is recovered under reduced pressure and is evaporated dichloroethanes, cools down 40 DEG C and 150mL ethyl acetate is added
50mL water is added in dissolution, and organic layer is added in the solution of sodium bisulfite of 200g30% by layering under stirring, is layered, water layer
75g concentrated hydrochloric acid is added, 65 DEG C are reacted 2 hours, are cooled to 35 DEG C, are added 5g decolorizing with activated carbon, filtrate is extracted with ethyl acetate, organic
Solvent is evaporated off in layer, and 30mL dichloroethanes crystallization is added, obtains yellow solid 24g.
Embodiment 2
1) synthesis of 2,5- dimethoxy bromobenzene
38.5g (278.6mmol) terephthaldehyde ether, 150g N, N- dimethyl formyl are sequentially added into 500ml four-hole bottle
Amine, for mechanical stirring to being completely dissolved, 49.6g (278.6mmol) N- bromo-succinimide is slowly added dropwise in 10 DEG C of cooling at room temperature
It with the prepared solution of n,N-Dimethylformamide, drips off within 1 hour or so, reacts 1 hour, be slowly added at room temperature to reaction solution
Dichloroethanes (100mL) extraction is added in 200ml water, and organic layer is extracted with saturated brine (100mL), organic layer anhydrous slufuric acid
Sodium is dried overnight, and is filtered, and filtrate revolving obtains brown color liquid 51g.
2) synthesis of 2,5- dimethoxy benzaldehyde
11g (460mmol) magnesium powder, 50g tetrahydrofuran are added into 500mL four-hole bottle, nitrogen protection is dripped under mechanical stirring
The solution 10 for adding 50g (230.3mmol) 2,5- dimethoxy bromobenzene and tetrahydrofuran to prepare drips, and after reaction causes, maintains the reflux for
Continue to be added dropwise, be dripped off in 3 hours.It flows back again 0.5 hour.Anti- liquid is cooled to 10 DEG C hereinafter, 42g (574mmol) N, N- bis- is added dropwise
Methylformamide is stirred to react 1 hour after dripping.It is slowly added into 100g water under control 30, adjusts pH=with hydrochloric acid at room temperature
3, the extraction of 100mL dichloroethanes is added, organic layer is extracted with saturated brine, is layered, is rotated to obtain brown liquid 35.1g.
3) synthesis of 2,5- 4-dihydroxy benzaldehyde
Addition 43.5g (261.7mmol) 2,5- dimethoxy benzaldehyde into 500mL four-hole bottle, 250mL dichloroethanes,
76.4g (523.4mmol) aluminum trichloride (anhydrous) is added under mechanical stirring in nitrogen protection by several times, reacts 3 hours for 65 DEG C after adding,
Cooling down is slowly added into 150mL water to 10 DEG C, is recovered under reduced pressure and is evaporated dichloroethanes, cools down 40 DEG C and 150mL ethyl acetate is added
50mL water is added in dissolution, and organic layer is added in the solution of sodium bisulfite of 200g30% by layering under stirring, is layered, water layer
75g concentrated hydrochloric acid is added, is reacted 2 hours for 65 DEG C of heating under nitrogen, is cooled to 35 DEG C, adds 5g decolorizing with activated carbon, filtrate acetic acid second
Ester extraction, organic layer saturated salt washing, rotates recycling design, and 30mL dichloroethanes crystallization is added, obtains yellow solid 23.5g.
The above, embodiment is only that preferred embodiments of the present invention will be described, not to of the invention
Range is defined, and under the premise of not departing from the spirit of the technology of the present invention, this field engineers and technicians are to skill of the invention
The various changes and improvements that art scheme is made should all fall into claims of the present invention and determine in protection scope.
Claims (2)
- The preparation method of 1.2,5- 4-dihydroxy benzaldehydes, includes the following steps:First step bromination reaction: using terephthaldehyde's ether as raw material, using n,N-Dimethylformamide as solvent, with N- bromo succinyl Imines (NBS) is bromide reagent, is reacted 3~5 hours, and reaction solution extracts through washing, layering, halogenated alkane, solvent is evaporated off, and is obtained The molar ratio of liquid 2,5- dimethoxy bromobenzene, n,N-Dimethylformamide used and terephthaldehyde's ether is 10~15:1；It is used The molar ratio of N- bromo-succinimide and terephthaldehyde's ether is 0.8~1:1；Second step grignard reaction (Grignard reaction):, will be 2,5- obtained by the first step with tetrahydrofuran (THF) for solvent Dimethoxy bromobenzene is reacted with magnesium powder, and product reacts 1~2 hour with n,N-Dimethylformamide (DMF) again, and reaction solution is through water Solution adjusts reaction solution pH=3, and halogenated alkane, which is extracted, is layered, saturated salt is washed, solvent is evaporated off obtains 2,5- dimethoxy benzaldehyde, 1.1~1.5:1 of molar ratio of magnesium powder used and 2,5- dimethoxy bromobenzene；N,N-dimethylformamide used and 2,5- dimethoxy 2~2.2:1 of molar ratio of bromide benzene；Third step demethylating reaction:, using halogenated alkane as solvent, by 2,5- dimethoxy benzaldehyde obtained by second step and anhydrous three 2,5- 4-dihydroxy benzaldehyde, halogenated alkane used and 2,5- dimethoxy benzene first are obtained through demethylating reaction under the action of aluminium chloride The weight ratio of aldehyde is 7~10:1, and aluminum trichloride (anhydrous) used and 2, the molar ratio of 5- dimethoxy benzaldehyde is 2~2.2:1.
- 2. the preparation method of 2,5- 4-dihydroxy benzaldehyde according to claim 1, it is characterised in that the first step, second step, Used halogenated alkane is methylene chloride, chloroform, 1,2- dichloroethanes in three steps.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110862292A (en) * | 2019-11-19 | 2020-03-06 | 中国科学院兰州化学物理研究所 | Preparation method of 1-aryl-1, 2-dibromoethane |
| CN113121325A (en) * | 2021-03-23 | 2021-07-16 | 西安拓超生物科技有限公司 | Preparation method of 2,5-dihydroxy benzaldehyde |
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| WO2008119793A1 (en) * | 2007-04-02 | 2008-10-09 | Esteve Química, S.A. | Process for the preparation of entacapone and intermediates thereof |
| CN104211582A (en) * | 2013-05-30 | 2014-12-17 | 江西益泰宁药业有限公司 | Synthesis method of resveratrol |
| CN105503551A (en) * | 2015-12-21 | 2016-04-20 | 索安克（上海）投资有限公司 | Method for preparing 2,3-dimethyl benzaldehyde |
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2019
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2008119793A1 (en) * | 2007-04-02 | 2008-10-09 | Esteve Química, S.A. | Process for the preparation of entacapone and intermediates thereof |
| CN104211582A (en) * | 2013-05-30 | 2014-12-17 | 江西益泰宁药业有限公司 | Synthesis method of resveratrol |
| CN105503551A (en) * | 2015-12-21 | 2016-04-20 | 索安克（上海）投资有限公司 | Method for preparing 2,3-dimethyl benzaldehyde |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110862292A (en) * | 2019-11-19 | 2020-03-06 | 中国科学院兰州化学物理研究所 | Preparation method of 1-aryl-1, 2-dibromoethane |
| CN113121325A (en) * | 2021-03-23 | 2021-07-16 | 西安拓超生物科技有限公司 | Preparation method of 2,5-dihydroxy benzaldehyde |
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Application publication date: 20191015 |