CN110256214A - A method of synthesis 3,5- 4-dihydroxy benzaldehyde - Google Patents
A method of synthesis 3,5- 4-dihydroxy benzaldehyde Download PDFInfo
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- C07C37/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring
- C07C37/001—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain
- C07C37/002—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain by transformation of a functional group, e.g. oxo, carboxyl
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Abstract
The invention discloses a kind of synthesis 3, the method of 5- 4-dihydroxy benzaldehyde, synthetic route are as follows: first 3,5- dihydroxy-benzoic acid obtains intermediate B under the action of sodium borohydride, dimethyl suflfate, trimethylborate, then intermediate B obtains compound C under the action of chromium trioxide and sulfuric acid, that is 3,5- 4-dihydroxy benzaldehyde；Reaction equation are as follows:Synthesis condition of the invention is mild, and reaction yield is high, and this method concise in technology, raw material it is cheap and easy to get, it is easy to operate, be particularly well suited for industrialized production, there is very extensive industrial applications prospect and market value.
Description
Technical field
The invention belongs to technical field of organic synthesis, in particular to a kind of method for synthesizing 3,5- 4-dihydroxy benzaldehyde.
Background technique
3,5- 4-dihydroxy benzaldehydes are a kind of important medicine intermediates and chemical intermediate, in many natural drug activity
There are the structure fragments in ingredient.Such as the non-flavonoids polyphenol with anticancer, anti-oxidant, hypolipidemic activity stilbene class formation
It closes object resveratrol (D), just contains the structure (CN105622350A) of 3,5- 4-dihydroxy benzaldehyde.For another example from Cortex Mori
That extracts has anti-diabetic, anti arteriosclerosis and the treatment active compound Moracin M (E) of central nervous system disease
Contain 3,5- 4-dihydroxy benzaldehyde similar structures (CN104447646A).In addition it is also deposited in New LED material molecule intermediate F
In 3,5- 4-dihydroxy benzaldehyde structure (J.Mater.Chem., 2000,10,867-871).
The comparison reported in the literature of 3,5- 4-dihydroxy benzaldehydes is more, reports if any document (CN107951870) with 3,5- diformazan
Oxygroup benzaldehyde is that raw material synthesizes 3,5- 4-dihydroxy benzaldehyde under the action of anhydrous aluminum chloride, but this method there are raw material at
The disadvantages of this height, reaction yield bottom, industry's enlarging production is not suitable for it.For another example have document (Chemische Berichte,
1941,74,869-872) it reports with 3,5- diacetoxy chlorobenzoyl chloride as raw material, synthesizes 3,5- bis- under palladium catalyst effect
Hydroxy benzaldehyde, but the factors such as this method needs to use precious metals palladium catalyst, and reaction temperature is excessively high, and yield is low, constrain
The application of this method industry's enlarging production.
The present invention use for reference existing document (Tetrahedron Letters., 2008,49,3260-3263；
J.Mater.Chem., 2000,10,867-871) with cheap 3,5- dihydroxy-benzoic acid (A) be raw material in sodium borohydride, sulphur
What dimethyl phthalate, trimethylborate acted on lower high yield obtains intermediate (B), then under the action of chromium trioxide and sulfuric acid
To target compound 3,5- 4-dihydroxy benzaldehyde (C), this method is with other literature procedures with raw material is cheap and easy to get, reacts
The advantages that mild condition, reaction yield are high, post-processing operation is easy is suitable for industrial amplification production.
Summary of the invention
In order to solve the problems in the prior art, the present invention provides a kind of method for synthesizing 3,5- 4-dihydroxy benzaldehyde, with
Applied to industry's enlarging production.
To achieve the above object, the technical solution adopted by the present invention are as follows:
A kind of method synthesizing 3,5- 4-dihydroxy benzaldehyde,
Synthetic route are as follows: intermediate (B) is obtained for raw material under the action of catalyst I with 3,5- dihydroxy-benzoic acid (A),
Then intermediate (B) obtains target compound 3,5- 4-dihydroxy benzaldehyde (C) under the action of catalyst II；
Reaction equation is as follows:
Preferably, the catalyst I is sodium borohydride, dimethyl suflfate and trimethylborate.
Preferably, the catalyst II is chromium trioxide and sulfuric acid.
Preferably, the sulfuric acid is the concentrated sulfuric acid.
It further, is raw material in sodium borohydride, dimethyl suflfate and trimethylborate with 3,5- dihydroxy-benzoic acid (A)
Under the action of obtain intermediate (B) yield be >=85%；It is raw material under the action of chromium trioxide and sulfuric acid with intermediate (B)
The yield for obtaining target compound 3,5- 4-dihydroxy benzaldehyde (C) is >=80%.
A kind of method synthesizing 3,5- 4-dihydroxy benzaldehyde, comprising the following steps:
Step 1, under nitrogen protection, at 0 DEG C, dimethyl suflfate is added drop-wise to the tetrahydrofuran solution of sodium borohydride
In, 0 DEG C of progress first time stirring is kept, then at room temperature, second is carried out and stirs, stirring to mixture is generated without gas；
The tetrahydrofuran solution of 3,5- dihydroxy-benzoic acid and trimethylborate is added dropwise thereto again, carries out third time stirring at room temperature；
After reaction, 0 DEG C of system is kept, deionized water is added thereto, carries out the 4th stirring, then boil off tetrahydrofuran, then
It is extracted with ethyl acetate, then is successively cleaned with saturated sodium bicarbonate solution, saturated salt solution, finally dry concentration, obtains white
Solid B；
Step 2, the concentrated sulfuric acid is added drop-wise in the solution of saturation chromium trioxide, Jones reagent is made；By the tetrahydro of intermediate B
Tetrahydrofuran solution is cooled to 0 DEG C, and the Jones reagent prepared is added dropwise thereto, is kept for 0 DEG C carry out the 5th stirring；Reaction knot
Beam is added dropwise saturated sodium bicarbonate solution until bubble-free generates thereto at 0 DEG C, then ethyl acetate is added thereto, into
Row the 6th time stirring, is obtained by filtration filtrate；Filtrate is extracted with deionized water, and water phase is extracted with ethyl acetate again, is harmonious organic
And dry concentration, obtain brown solid C.
Preferably, in the step 1, the time of stirring is 1 hour for the first time, and the time of second of stirring is 4 hours, the
The time of triple mixing is 5 hours, and the time of the 4th stirring is 0.5 hour；
In the step 1, the time that dimethyl suflfate is added dropwise is 1 hour；3,5- dihydroxy-benzoic acid and boric acid three is added dropwise
The time of the tetrahydrofuran solution of methyl esters is 0.5 hour；
In the step 1, tetrahydrofuran is boiled off using Rotary Evaporators, is carried out at 50 DEG C；Dry concentration is using rotation
Evaporimeter carries out at 45 DEG C；
In the step 1, after extraction, first use saturated sodium bicarbonate solution backwash 3 times, then with saturated salt solution backwash 3 times.
Preferably, in the step 2, the time of the 5th stirring is 2 hours, and the time of the 6th stirring is 0.5 hour；
In the step 2, the time for adding of Jones reagent is 0.5 hour；Filtrate is extracted 3 times with deionized water；Organic phase
Merge dry concentration and use Rotary Evaporators, is carried out at 45 DEG C.
Compared with prior art, the invention has the following advantages:
The synthesis condition that the present invention synthesizes 3,5- 4-dihydroxy benzaldehyde technique is mild, high income, and this method concise in technology,
Raw material is cheap and easy to get, it is easy to operate, be particularly well suited for industrialized production, there is very extensive industrial applications prospect and market
Value.
Detailed description of the invention
Fig. 1 is the H-NMR spectrum for the product Compound B that step 1 obtains in the embodiment of the present invention 1；
Fig. 2 is the H-NMR spectrum for the product Compound C that step 2 obtains in the embodiment of the present invention 1.
Specific embodiment
Below with reference to embodiment, the present invention will be further explained.
Embodiment 1
A kind of method synthesizing 3,5- 4-dihydroxy benzaldehyde,
Synthetic route are as follows: intermediate (B) is obtained for raw material under the action of catalyst I with 3,5- dihydroxy-benzoic acid (A),
Then intermediate (B) obtains target compound 3,5- 4-dihydroxy benzaldehyde (C) under the action of catalyst II；
Reaction equation is as follows:
Specific synthetic method the following steps are included:
A kind of method synthesizing 3,5- 4-dihydroxy benzaldehyde, comprising the following steps:
Step 1, under nitrogen protection, at 0 DEG C, dimethyl suflfate (2kg) is added drop-wise to the four of sodium borohydride (615g)
In hydrogen furans (1kg) solution, time for adding 1 hour, is kept for 0 DEG C stir 1 hour, then at room temperature, extremely mixed within stirring 4 hours
Object is generated without gas；The tetrahydrofuran of 3,5- dihydroxy-benzoic acid (1kg) and trimethylborate (2kg) is added dropwise thereto again
(1kg) solution time for adding 0.5 hour, stirs 5 hours at room temperature；After reaction, 0 DEG C of system is kept, is added goes thereto
Ionized water (1kg) stirs 0.5 hour, using Rotary Evaporators, tetrahydrofuran is boiled off at 50 DEG C, then uses ethyl acetate
(2kg) extraction, then successively cleaned instead with saturated sodium bicarbonate solution (each 2kg) backwash 3 times, saturated salt solution (each 2kg)
It washes 3 times, finally uses Rotary Evaporators, dry concentration, obtains white solid B (770g), yield 85%, such as Fig. 1 at 45 DEG C
It is shown, the H-NMR spectrum for the product Compound B that step 1 obtains in embodiment 1；1H-NMR(DMSO-d6,600MHz):δ9.08
(2H, s), 6.19 (2H, s), 6.08 (2H, s), 5.01 (1H, t, J=6Hz), 4.32 (1H, d, J=6Hz)；
Step 2, the concentrated sulfuric acid (1.5kg) is added drop-wise in the solution of saturation chromium trioxide (770g), Jones reagent is made；It will
Tetrahydrofuran (1kg) solution of intermediate B (770g) is cooled to 0 DEG C, and the Jones reagent prepared is added dropwise thereto, is added dropwise
Time 0.5 hour, kept for 0 DEG C stir 2 hours；Reaction terminates, and saturated sodium bicarbonate solution (3kg) is added dropwise thereto at 0 DEG C
Ethyl acetate (2kg) is added until bubble-free generates, then thereto, stirs 0.5 hour, filtrate is obtained by filtration；Filtrate spends
Ionized water (each 1kg) extracts 3 times, and water phase uses ethyl acetate (2kg) extraction primary again, and organic phase is merged, and is steamed using rotation
Instrument is sent out, dry concentration, obtains brown solid C (610g), yield 80% at 45 DEG C, as shown in Fig. 2, step 2 obtains in embodiment 1
The H-NMR spectrum of the product Compound C arrived；
1H-NMR (DMSO-d6,600MHz): δ 9.78 (1H, m), 6.74 (2H, d, J=3Hz), 6.53 (1H, dd, J=
3Hz)。
The above is only a preferred embodiment of the present invention, it should be pointed out that: for the ordinary skill people of the art
For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications are also answered
It is considered as protection scope of the present invention.
Claims (8)
1. a kind of method for synthesizing 3,5- 4-dihydroxy benzaldehyde, which is characterized in that
Synthetic route are as follows: intermediate (B) is obtained for raw material under the action of catalyst I with 3,5- dihydroxy-benzoic acid (A), then
Intermediate (B) obtains target compound 3,5- 4-dihydroxy benzaldehyde (C) under the action of catalyst II；
Reaction equation is as follows:
2. the method for synthesis 3,5- 4-dihydroxy benzaldehyde according to claim 1, which is characterized in that the catalyst I is
Sodium borohydride, dimethyl suflfate and trimethylborate.
3. the method for synthesis 3,5- 4-dihydroxy benzaldehyde according to claim 1, which is characterized in that the catalyst II is
Chromium trioxide and sulfuric acid.
4. the method for synthesis 3,5- 4-dihydroxy benzaldehyde according to claim 4, which is characterized in that the sulfuric acid is dense sulphur
Acid.
5. the method for synthesis 3,5- 4-dihydroxy benzaldehyde according to claim 1, which is characterized in that with 3,5- dihydroxy benzenes
Formic acid (A) be raw material obtained under the action of sodium borohydride, dimethyl suflfate and trimethylborate intermediate (B) yield be >=
85%；It is that raw material obtains target compound 3,5- 4-dihydroxy benzaldehyde under the action of chromium trioxide and sulfuric acid with intermediate (B)
(C) yield is >=80%.
6. -5 any synthesis 3 according to claim 1, the method for 5- 4-dihydroxy benzaldehyde, which is characterized in that including following
Step:
Step 1, under nitrogen protection, at 0 DEG C, dimethyl suflfate is added drop-wise in the tetrahydrofuran solution of sodium borohydride, is protected
0 DEG C of progress first time stirring is held, then at room temperature, second is carried out and stirs, stirring to mixture is generated without gas；Again to it
The middle tetrahydrofuran solution that 3,5- dihydroxy-benzoic acid and trimethylborate is added dropwise, carries out third time stirring at room temperature；Reaction knot
Shu Hou is kept for 0 DEG C of system, and deionized water is added thereto, is carried out the 4th stirring, then boil off tetrahydrofuran, is then used acetic acid
Ethyl ester extraction, then successively cleaned with saturated sodium bicarbonate solution, saturated salt solution, finally dry concentration, obtains white solid B；
Step 2, the concentrated sulfuric acid is added drop-wise in the solution of saturation chromium trioxide, Jones reagent is made；By the tetrahydrofuran of intermediate B
Solution is cooled to 0 DEG C, and the Jones reagent prepared is added dropwise thereto, is kept for 0 DEG C carry out the 5th stirring；Reaction terminates,
Saturated sodium bicarbonate solution is added dropwise thereto at 0 DEG C until bubble-free generates, then ethyl acetate is added thereto, carries out the
Six stirrings, are obtained by filtration filtrate；Filtrate is extracted with deionized water, and water phase is extracted with ethyl acetate again, organic phase is merged dry
Dry concentration obtains brown solid C.
7. the method for synthesis 3,5- 4-dihydroxy benzaldehyde according to claim 6, which is characterized in that in the step 1, the
The time once stirred is 1 hour, and the time of second of stirring is 4 hours, and the time of third time stirring is 5 hours, the 4th time
The time of stirring is 0.5 hour；
In the step 1, the time that dimethyl suflfate is added dropwise is 1 hour；3,5- dihydroxy-benzoic acid and trimethylborate is added dropwise
Tetrahydrofuran solution time be 0.5 hour；
In the step 1, tetrahydrofuran is boiled off using Rotary Evaporators, is carried out at 50 DEG C；Dry concentration uses rotary evaporation
Instrument carries out at 45 DEG C；
In the step 1, after extraction, first use saturated sodium bicarbonate solution backwash 3 times, then with saturated salt solution backwash 3 times.
8. the method for synthesis 3,5- 4-dihydroxy benzaldehyde according to claim 6, which is characterized in that in the step 2, the
The time of five stirrings is 2 hours, and the time of the 6th stirring is 0.5 hour；The time for adding of Jones reagent is 0.5 hour；
Filtrate is extracted 3 times with deionized water；Organic phase merges dry concentration and uses Rotary Evaporators, carries out at 45 DEG C.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001199916A (en) * | 2000-01-17 | 2001-07-24 | Honshu Chem Ind Co Ltd | Method for producing hydroxybenzyl alcohols |
| CN103130617A (en) * | 2013-03-07 | 2013-06-05 | 江苏集贤绿色化学科技研究院有限公司 | Synthetic method of 3,5-dihydroxybenzyl alcohol |
| CN105884580A (en) * | 2014-11-25 | 2016-08-24 | 天津工业大学 | Preparation method of 3,5-dihydroxybenzyl alcohol |
| CN107162883A (en) * | 2017-05-22 | 2017-09-15 | 三峡大学 | A kind of preparation method of 2,4 4-dihydroxy benzaldehyde |
| CN109867592A (en) * | 2017-12-04 | 2019-06-11 | 南京科技职业学院 | A kind of synthesis technology of 3,5- 4-dihydroxy benzaldehyde |
-
2019
- 2019-07-26 CN CN201910681378.5A patent/CN110256214A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001199916A (en) * | 2000-01-17 | 2001-07-24 | Honshu Chem Ind Co Ltd | Method for producing hydroxybenzyl alcohols |
| CN103130617A (en) * | 2013-03-07 | 2013-06-05 | 江苏集贤绿色化学科技研究院有限公司 | Synthetic method of 3,5-dihydroxybenzyl alcohol |
| CN105884580A (en) * | 2014-11-25 | 2016-08-24 | 天津工业大学 | Preparation method of 3,5-dihydroxybenzyl alcohol |
| CN107162883A (en) * | 2017-05-22 | 2017-09-15 | 三峡大学 | A kind of preparation method of 2,4 4-dihydroxy benzaldehyde |
| CN109867592A (en) * | 2017-12-04 | 2019-06-11 | 南京科技职业学院 | A kind of synthesis technology of 3,5- 4-dihydroxy benzaldehyde |
Non-Patent Citations (3)
| Title |
|---|
| LUPTON JM等: "Electroluminescence from a new distyrylbenzene based triazine dendrimer", 《JOURNAL OF MATERIALS CHEMISTRY 》 * |
| WANG LIJUN: "Carbon-carbon bond construction using electron transfer initiated cyclization reactions. Ruthenium-catalyzed hydroesterification and its application towards the synthesis of integramycin", 《DISS. ABSTR. INT.》 * |
| ZHOU YUHAN等: "A convenient method to reduce hydroxyl-substituted aromatic carboxylic acid with NaBH4/Me2SO4/B(OMe)3", 《TETRAHEDRON LETTERS》 * |
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Application publication date: 20190920 |