CN107935984B - A kind of preparation method of 3- thiophenecarboxaldehyde - Google Patents
A kind of preparation method of 3- thiophenecarboxaldehyde Download PDFInfo
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- CN107935984B CN107935984B CN201711433755.0A CN201711433755A CN107935984B CN 107935984 B CN107935984 B CN 107935984B CN 201711433755 A CN201711433755 A CN 201711433755A CN 107935984 B CN107935984 B CN 107935984B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/22—Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
Abstract
The present invention relates to technical field of organic synthesis, more particularly, to a kind of preparation method of 3- thiophenecarboxaldehyde.The preparation method of the 3- thiophenecarboxaldehyde includes the following steps: after reacting 1,1,3,3- tetramethoxy propane under acid condition that hybrid reaction, post-processing obtain 3- thiophenecarboxaldehyde under alkaline condition with-two sulphur -2,5- glycol of Isosorbide-5-Nitrae.The preparation method of 3- thiophenecarboxaldehyde of the invention, which only passes through, is simply mixed reaction, and the 3- thiophenecarboxaldehyde product that purity is more than 98% can be prepared, and ultralow temperature is not necessarily in preparation process and is reacted using hazardous agents, production safety coefficient is improved.And preparation method of the invention is easy to operate, and raw material is easy to get, and has saved operating cost and cost of material, is suitable for industrialized production 3- thiophenecarboxaldehyde.
Description
Technical field
The present invention relates to technical field of organic synthesis, more particularly, to a kind of preparation method of 3- thiophenecarboxaldehyde.
Background technique
3- thiophenecarboxaldehyde is a kind of colourless or weak yellow liquid, and solution colour gradually deepens after meeting light, has irritation gas
Taste is soluble in the organic solvents such as alcohol, benzene, ether, methylene chloride, is slightly soluble in water.3- thiophenecarboxaldehyde is in the important medicine of one kind
Mesosome is mainly used for amine antimicrobial anti-inflammatory drug, for treating staphylococcus, streptococcus, pneumococcus and meningococcal sense
Dye.The production capacity of Chinese Enterprises thiophenecarboxaldehyde is smaller at present, constrains the development of such medicine, is badly in need of a kind of new suitable industry
The production method of change.
In the prior art, there is document (Synthetic Communications, 2001,31 (10), 1527-1530) report
The synthetic method of road 3- thiophenecarboxaldehyde is, with-two sulphur -2,5- glycol of Isosorbide-5-Nitrae for raw material, first to synthesize 2,5- dihydro -3- thiophenecarboxaldehyde,
3- thiophenecarboxaldehyde is synthesized under conditions of -35 DEG C with chlorosulfuric acid again.The route first step needs steam distillation, is not easy to amplify,
Second step needs react under the conditions of extremely low temperature, once temperature is slightly higher easily to generate impurity, to equipment requirement harshness, need
Special Cryo Equipment consumes energy larger, is also not easy to amplify.There are also document (Bulletin of the Korean Chemical
Society, 2013,34 (4), 1170-1174) it reports, using 3 bromo thiophene as raw material, reacted at -78 DEG C with n-BuLi
The temperature and its low, unsuitable industrialization needed to 3- thiophenecarboxaldehyde, this route, also, n-BuLi meets the poles such as water, oxide
Easy burn is easy kindling, uses danger close.
In view of this, the present invention is specifically proposed.
Summary of the invention
It is easy to operate the purpose of the present invention is to provide a kind of preparation method suitable for industrialized production 3- thiophenecarboxaldehyde
Economy, high income, purity is high, to solve, extremely low reaction temperature existing in the prior art, reagent safety is low and is not easy
The technical issues of amplification.
In order to realize above-mentioned purpose of the invention, the following technical scheme is adopted:
A kind of preparation method of 3- thiophenecarboxaldehyde, includes the following steps:
After 1,1,3,3- tetramethoxy propane is reacted under acid condition, with-two sulphur -2,5- glycol of Isosorbide-5-Nitrae in alkaline item
Hybrid reaction under part, post-processing obtain 3- thiophenecarboxaldehyde.
The preparation method of 3- thiophenecarboxaldehyde of the invention, which only passes through, is simply mixed reaction, and purity can be prepared
3- thiophenecarboxaldehyde product more than 98%, and reacted without ultralow temperature and in preparation process using hazardous agents, improve life
Produce safety coefficient.And preparation method of the invention is easy to operate, and raw material is easy to get, and has saved operating cost and cost of material, fits
For industrialized production 3- thiophenecarboxaldehyde.
1,1,3,3- tetramethoxy propane under the action of an acid, can react generation malonaldehyde at room temperature, produce in centre
- two sulphur -2,5- glycol of Isosorbide-5-Nitrae is directly added into object malonaldehyde, in the presence of alkali, reaction generates 3- thiophenecarboxaldehyde.
1,1,3,3- tetramethoxy propane and-two sulphur -2,5- diol starting materials of Isosorbide-5-Nitrae be easy to get and safety, and reaction process without
Ultralow temperature or superhigh temperature are needed, production safety coefficient is improved, and without expensive catalyst etc., both reduces cost of material,
It in turn avoids catalyst in last handling process and is not easy the problem of removing.
Preferably, 1, reaction temperature of 1,3, the 3- tetramethoxy propane under acid condition is 20-40 DEG C.It is furthermore preferred that
Reaction time of the 1,1,3,3- tetramethoxy propane under acid condition is 2-3h.
It preferably, is 50-70 DEG C with the reaction temperature of-two sulphur -2,5- glycol of Isosorbide-5-Nitrae under alkaline condition.It is furthermore preferred that with
The reaction time of bis- sulphur -2,5- glycol of 1,4- under alkaline condition is 4-6h.
Preferably,-two sulphur -2,5- bis- pure and mild 1 of Isosorbide-5-Nitrae, the molar ratio of 1,3,3- tetramethoxy propane are 1 ﹕ (1.5-
5).It is furthermore preferred that-two sulphur -2,5- bis- pure and mild 1 of Isosorbide-5-Nitrae, the molar ratio of 1,3,3- tetramethoxy propane is 1 ﹕ (2-4).
Preferably, 1, the acid that 1,3,3- tetramethoxy propane reacts under acid condition includes hydrochloric acid, sulfuric acid, to toluene sulphur
One of acid and sulfonic acid are a variety of.
Preferably, described 1,1,3,3- tetramethoxy propane and sour molar ratio are (2-4) ﹕ (0.2-0.4).
Preferably, mixed in hydrochloric acid reaction is added into 1,1,3,3- tetramethoxy propane.It is furthermore preferred that described 1,1,3,3-
The molar ratio of tetramethoxy propane and hydrochloric acid is (2-4) ﹕ (0.2-0.4).
Preferably, the mass fraction of the hydrochloric acid is 8%-15%.
Preferably, with-two sulphur -2,5- glycol of Isosorbide-5-Nitrae under alkaline condition hybrid reaction alkali be organic base.It is furthermore preferred that
The organic base includes one of diethylamine, triethylamine, piperidines, pyridine and DBU or a variety of.It is furthermore preferred that the Isosorbide-5-Nitrae-two
The molar ratio of sulphur -2,5- glycol and alkali is 1 ﹕ (0.5-1).
Preferably, the method for the post-processing includes the following steps: for the mixture after reaction to be added to the water and be quenched,
Then organic solvent extraction is added and separates organic phase, is concentrated to get the 3- thiophenecarboxaldehyde.
Preferably, the organic solvent includes one of ethyl acetate, toluene and isohexane or a variety of.
The mixture for the thiophenecarboxaldehyde containing 3- that reaction obtains is added in cold water, mode is quenched, reduces by-product
It generates, selects model, substantially increase product yield and purity.
Preferably, the mass ratio of the organic solvent and-two sulphur -2,5- glycol of Isosorbide-5-Nitrae is (8-15) ﹕ 1.
By selecting suitable extraction split-phase solvent, available purity is more than 98% product, and yield is higher.
Preferably, the mixture after reaction is added in cold water and is quenched.
Preferably, the temperature of the cold water is 3-12 DEG C.Preferably, the temperature of the cold water is 5-10 DEG C.
Compared with prior art, the invention has the benefit that
(1) preparation method of the invention, which only passes through, is simply mixed reaction, and it is more than 98% that purity, which can be prepared,
3- thiophenecarboxaldehyde, and the high income of 3- thiophenecarboxaldehyde；
(2) preparation method of the invention is easy to operate without reacting under condition of ultralow temperature, is not necessarily to Cryo Equipment, saves
Operating cost and energy consumption；
(3) preparation method of the invention is using the pure and mild 1,1,3,3- tetramethoxy propane of bis- sulphur -2,5- of 1,4- two as former
Material, raw material are easy to get, do not need hazardous agents, effectively increase production safety coefficient；
(4) preparation method simple economy of the invention is suitable for industrialized production 3- thiophenecarboxaldehyde.
Detailed description of the invention
It, below will be to specific in order to illustrate more clearly of the specific embodiment of the invention or technical solution in the prior art
Embodiment or attached drawing needed to be used in the description of the prior art be briefly described, it should be apparent that, it is described below
Attached drawing is some embodiments of the present invention, for those of ordinary skill in the art, before not making the creative labor
It puts, is also possible to obtain other drawings based on these drawings.
Fig. 1 is the gas chromatogram for the 3- thiophenecarboxaldehyde that the embodiment of the present invention 1 is prepared；
Fig. 2 is the gas chromatogram for the 3- thiophenecarboxaldehyde that the embodiment of the present invention 2 is prepared；
Fig. 3 is the gas chromatogram for the 3- thiophenecarboxaldehyde that the embodiment of the present invention 3 is prepared；
Fig. 4 is the gas chromatogram for the 3- thiophenecarboxaldehyde that the embodiment of the present invention 4 is prepared.
Specific embodiment
Technical solution of the present invention is clearly and completely described below in conjunction with the drawings and specific embodiments, but
Be it will be understood to those of skill in the art that it is following described embodiments are some of the embodiments of the present invention, rather than it is whole
Embodiment is merely to illustrate the present invention, and is not construed as limiting the scope of the invention.Based on the embodiments of the present invention, ability
Domain those of ordinary skill every other embodiment obtained without making creative work, belongs to guarantor of the present invention
The range of shield.The person that is not specified actual conditions in embodiment, carries out according to conventional conditions or manufacturer's recommended conditions.Agents useful for same
Or production firm person is not specified in instrument, is the conventional products that can be obtained by commercially available purchase.
The preparation method of 3- thiophenecarboxaldehyde of the invention, includes the following steps:
(a) acid is added to 1,1,3,3- tetramethoxy propane under agitation, control reaction temperature is 20-40 DEG C, is stirred
Mix reaction 2-3h；
(b) the pure and mild alkali of-two sulphur -2,5- of Isosorbide-5-Nitrae bis- is added into mixture obtained in step (a), control reaction temperature is
50-70 DEG C, 4-6h is reacted, 3- thiophenecarboxaldehyde solution is obtained；
(c) 3- thiophenecarboxaldehyde solution is post-processed, obtains 3- thiophenecarboxaldehyde；Specifically, 3- thiophenecarboxaldehyde solution is added
It is quenched in water, organic solvent extraction is then added and separates organic phase, washes organic phase, is concentrated to get the 3- thiophene first
Aldehyde.
Wherein,-two sulphur -2,5- glycol of Isosorbide-5-Nitrae, 1,1,3,3- tetramethoxy propane, acid, alkali molar ratio be preferably 1 ﹕
(2-4) ﹕ (0.2-0.4) ﹕ (0.5-1).In this proportional region, it can guarantee the yield of 3- thiophenecarboxaldehyde being prepared
Height, and purity is good, and the utilization rate of raw material maximizes, and production cost is relatively minimum.
The acid is preferably one of hydrochloric acid, sulfuric acid, p-methyl benzenesulfonic acid and sulfonic acid or a variety of.
The alkali is preferably in diethylamine, triethylamine, piperidines, pyridine and DBU (11 carbon -7- alkene of 1,8- diazabicylo)
It is one or more.
In post-processing, the organic solvent is preferably one of ethyl acetate, toluene and isohexane or a variety of.
The synthetic route of 3- thiophenecarboxaldehyde of the invention is as follows:
1,1,3,3- tetramethoxy propane under the action of an acid, can react generation malonaldehyde at room temperature, produce in centre
- two sulphur -2,5- glycol of Isosorbide-5-Nitrae is directly added into object malonaldehyde, in the presence of alkali, reaction generates 3- thiophenecarboxaldehyde.
Embodiment 1
The preparation method of the 3- thiophenecarboxaldehyde of the present embodiment, includes the following steps:
(a) 1,1,3, the 3- tetramethoxy propane of 2mol is added into reaction vessel at room temperature, is added under agitation
(0.2mol refers to the amount of the substance of the HCl in the hydrochloric acid of addition, following embodiment to the hydrochloric acid that 0.2mol mass fraction is 10%
Similarly), it is 20 DEG C by reaction temperature control, is stirred to react 2h.
(b) the bis- sulphur -2,5- two of 1,4- that 1mol is added in the mixture in the reaction vessel into step (a) is pure and mild
Reaction temperature control is 60 DEG C, is stirred to react 4h, obtains 3- thiophenecarboxaldehyde solution by the triethylamine of 0.5mol.
(c) 3- thiophenecarboxaldehyde solution obtained in step (b) is added dropwise in 5 DEG C of cold water and is quenched, is added dropwise
Afterwards, ethyl acetate is added into system and extracts split-phase, collect organic phase；Water is added into organic phase to be washed, then split-phase
Collect organic phase；Organic phase is concentrated, excessive raw material and solvent are removed, obtains 3- thiophenecarboxaldehyde product, yield 62%.Its
In, the additional amount of the ethyl acetate for extraction is 8 times of the quality of-two sulphur -2,5- glycol of Isosorbide-5-Nitrae, for washing organic phase
The additional amount of water is 4 times of the quality of bis- sulphur -2,5- glycol of 1,4-.Referring to Fig. 1, it is the 3- thiophene that the present embodiment is prepared
The gas chromatogram of pheno formaldehyde, it can be seen that the purity for the 3- thiophenecarboxaldehyde product that the present embodiment is prepared is
98.97%.
Embodiment 2
The preparation method of the 3- thiophenecarboxaldehyde of the present embodiment, includes the following steps:
(a) 1,1,3, the 3- tetramethoxy propane of 3mol is added into reaction vessel at room temperature, is added under agitation
Reaction temperature control is 25 DEG C, is stirred to react 3h by the hydrochloric acid that 0.2mol mass fraction is 8%.
(b) the bis- sulphur -2,5- two of 1,4- that 1mol is added in the mixture in the reaction vessel into step (a) is pure and mild
Reaction temperature control is 70 DEG C, is stirred to react 4h, obtains 3- thiophenecarboxaldehyde solution by the diethylamine of 0.7mol.
(c) 3- thiophenecarboxaldehyde solution obtained in step (b) is added dropwise in 10 DEG C of cold water and is quenched, is added dropwise
Afterwards, toluene is added into system and extracts split-phase, collect organic phase；Water is added into organic phase to be washed, then split-phase is collected
Organic phase；Organic phase is concentrated, excessive raw material and solvent are removed, obtains 3- thiophenecarboxaldehyde product, yield 64%.Wherein,
The additional amount of toluene for extraction is 8 times of the quality of-two sulphur -2,5- glycol of Isosorbide-5-Nitrae, the addition of the water for washing organic phase
Amount is 4 times of the quality of bis- sulphur -2,5- glycol of 1,4-.Referring to Fig. 2, it is the 3- thiophenecarboxaldehyde that the present embodiment is prepared
Gas chromatogram, it can be seen that the purity for the 3- thiophenecarboxaldehyde product that the present embodiment is prepared is 98.98%.
Embodiment 3
The preparation method of the 3- thiophenecarboxaldehyde of the present embodiment, includes the following steps:
(a) 1,1,3, the 3- tetramethoxy propane of 4mol is added into reaction vessel at room temperature, is added under agitation
Reaction temperature control is 30 DEG C, is stirred to react 2.5h by the hydrochloric acid that the mass fraction of 0.3mol is 15%.
(b) the pure and mild 1mol of bis- sulphur -2,5- of 1,4- two of 1mol is added in the mixture in the reaction vessel into step (a)
Piperidines, by reaction temperature control be 50 DEG C, be stirred to react 5h, obtain 3- thiophenecarboxaldehyde solution.
(c) 3- thiophenecarboxaldehyde solution obtained in step (b) is added dropwise in 5 DEG C of cold water and is quenched, is added dropwise
Afterwards, isohexane is added into system and extracts split-phase, collect organic phase；Water is added into organic phase to be washed, then split-phase is received
Collect organic phase；Organic phase is concentrated, excessive raw material and solvent are removed, obtains 3- thiophenecarboxaldehyde product, yield 60%.Its
In, the additional amount of the isohexane for extraction is 12 times of the quality of-two sulphur -2,5- glycol of Isosorbide-5-Nitrae, for washing the water of organic phase
Additional amount be 6 times of quality of bis- sulphur -2,5- glycol of 1,4-.Referring to Fig. 3, it is the 3- thiophene that the present embodiment is prepared
The gas chromatogram of formaldehyde, it can be seen that the purity for the 3- thiophenecarboxaldehyde product that the present embodiment is prepared is 98.77%.
Embodiment 4
The preparation method of the 3- thiophenecarboxaldehyde of the present embodiment, includes the following steps:
(a) 1,1,3, the 3- tetramethoxy propane of 2mol is added into reaction vessel at room temperature, is added under agitation
Reaction temperature control is 40 DEG C, is stirred to react 2h by the hydrochloric acid that 0.4mol mass fraction is 12%.
(b) the bis- sulphur -2,5- two of 1,4- that 1mol is added in the mixture in the reaction vessel into step (a) is pure and mild
Reaction temperature control is 70 DEG C, is stirred to react 6h, obtains 3- thiophenecarboxaldehyde solution by the diethylamine of 0.8mol.
(c) 3- thiophenecarboxaldehyde solution obtained in step (b) is added dropwise in 5 DEG C of cold water and is quenched, is added dropwise
Afterwards, isohexane is added into system and extracts split-phase, collect organic phase；Water is added into organic phase to be washed, then split-phase is received
Collect organic phase；Organic phase is concentrated, excessive raw material and solvent are removed, obtains 3- thiophenecarboxaldehyde product, yield 65%.Its
In, the additional amount of the isohexane for extraction is 15 times of the quality of-two sulphur -2,5- glycol of Isosorbide-5-Nitrae, for washing the water of organic phase
Additional amount be 7 times of quality of bis- sulphur -2,5- glycol of 1,4-.Referring to Fig. 4, it is the 3- thiophene that the present embodiment is prepared
The gas chromatogram of formaldehyde, it can be seen that the purity for the 3- thiophenecarboxaldehyde product that the present embodiment is prepared is 98.62%.
Embodiment 5
3- thiophenecarboxaldehyde is prepared referring to preparation method as described in example 4, difference is only that,-two sulphur -2,5- glycol of Isosorbide-5-Nitrae
Molar ratio with 1,1,3,3- tetramethoxy propane is 1 ﹕ 1.5.It is characterized by identical gas chromatographic analysis, the present embodiment preparation
The purity of obtained 3- thiophenecarboxaldehyde product is 98.64%.
Embodiment 6
3- thiophenecarboxaldehyde is prepared referring to preparation method as described in example 4, difference is only that,-two sulphur -2,5- glycol of Isosorbide-5-Nitrae
Molar ratio with 1,1,3,3- tetramethoxy propane is 1 ﹕ 5.It is characterized by identical gas chromatographic analysis, the present embodiment is prepared into
The purity of the 3- thiophenecarboxaldehyde product arrived is 98.60%.
Embodiment 7
3- thiophenecarboxaldehyde is prepared referring to preparation method as described in example 4, difference is only that, the acid is sulfuric acid, described
The mass fraction of sulfuric acid is 15%.It is characterized by identical gas chromatographic analysis, the 3- thiophenecarboxaldehyde that the present embodiment is prepared
The purity of product is 98.73%.
Embodiment 8
3- thiophenecarboxaldehyde is prepared referring to preparation method as described in example 4, difference is only that, the acid is to toluene sulphur
Acid.It is characterized by identical gas chromatographic analysis, the purity for the 3- thiophenecarboxaldehyde product that the present embodiment is prepared is
98.66%.
Embodiment 9
3- thiophenecarboxaldehyde is prepared referring to preparation method as described in example 4, difference is only that, the acid is benzene sulfonic acid.It is logical
Identical gas chromatographic analysis characterization is crossed, the purity for the 3- thiophenecarboxaldehyde product that the present embodiment is prepared is 98.68%.
Embodiment 10
3- thiophenecarboxaldehyde is prepared referring to preparation method as described in example 4, difference is only that, the temperature of the cold water is 3
℃.It is characterized by identical gas chromatographic analysis, the purity for the 3- thiophenecarboxaldehyde product that the present embodiment is prepared is
98.78%.
Embodiment 11
3- thiophenecarboxaldehyde is prepared referring to preparation method as described in example 4, difference is only that, the temperature of the cold water is 12
℃.It is characterized by identical gas chromatographic analysis, the purity for the 3- thiophenecarboxaldehyde product that the present embodiment is prepared is
98.60%.
Comparative example 1
2,5- dihydro -3- thiophenecarboxaldehyde is first synthesized for raw material with-two sulphur -2,5- glycol of Isosorbide-5-Nitrae, then with chlorosulfuric acid at -35 DEG C
Under conditions of synthesize 3- thiophenecarboxaldehyde.
Comparative example 2
Using 3 bromo thiophene as raw material, at -78 DEG C and n-BuLi reacts to obtain 3- thiophenecarboxaldehyde.
Experimental example 1
For the 3- of the preparation method of 3- thiophenecarboxaldehyde and comparative example 1 and 2 described in comparative illustration various embodiments of the present invention
The preparation method of thiophenecarboxaldehyde, the carry out such as raw material and reaction condition and yield to various embodiments of the present invention and comparative example 1 and 2 are total
Knot, is shown in Table 1.
Raw material, reaction condition and the yield of the different preparation methods of table 1
It is found that raw material used by the preparation method of 3- thiophenecarboxaldehyde of the invention is easy to get from upper table, cost of material is low,
Safety coefficient is high, and reaction condition is simple, without the complex conditions such as superhigh temperature or low temperature, the yield of obtained 3- thiophenecarboxaldehyde
Higher, purity is higher.
Finally, it should be noted that the above embodiments are only used to illustrate the technical solution of the present invention., rather than its limitations；To the greatest extent
Pipe present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that: its according to
So be possible to modify the technical solutions described in the foregoing embodiments, or to some or all of the technical features into
Row equivalent replacement；And these are modified or replaceed, various embodiments of the present invention technology that it does not separate the essence of the corresponding technical solution
The range of scheme.
Claims (17)
1. a kind of preparation method of 3- thiophenecarboxaldehyde, which comprises the steps of:
Malonaldehyde is obtained after 1,1,3,3- tetramethoxy propane is reacted under acid condition, is existed with-two sulphur -2,5- glycol of Isosorbide-5-Nitrae
Hybrid reaction under alkaline condition, post-processing obtain 3- thiophenecarboxaldehyde；
The acid that the 1,1,3,3- tetramethoxy propane reacts under acid condition includes hydrochloric acid, sulfuric acid, p-methyl benzenesulfonic acid and benzene
One of sulfonic acid is a variety of；
With bis- sulphur -2,5- glycol of 1,4- under alkaline condition hybrid reaction alkali be organic base；The organic base include diethylamine,
One of triethylamine, piperidines, pyridine and DBU or a variety of.
2. the preparation method of 3- thiophenecarboxaldehyde according to claim 1, which is characterized in that 1,1,3,3- tetramethoxy propane
Reaction temperature under acid condition is 20-40 DEG C.
3. the preparation method of 3- thiophenecarboxaldehyde according to claim 2, which is characterized in that 1,1,3,3- tetramethoxy propane
Reaction time under acid condition is 2-3h.
4. the preparation method of 3- thiophenecarboxaldehyde according to claim 1, which is characterized in that with-two sulphur -2,5- glycol of Isosorbide-5-Nitrae
Reaction temperature under alkaline condition is 50-70 DEG C.
5. the preparation method of 3- thiophenecarboxaldehyde according to claim 4, which is characterized in that with-two sulphur -2,5- glycol of Isosorbide-5-Nitrae
Reaction time under alkaline condition is 4-6h.
6. the preparation method of 3- thiophenecarboxaldehyde according to claim 1, which is characterized in that-two sulphur -2,5- bis- of Isosorbide-5-Nitrae
The molar ratio of pure and mild 1,1,3,3- tetramethoxy propane is 1 ﹕ (1.5-5).
7. the preparation method of 3- thiophenecarboxaldehyde according to claim 6, which is characterized in that-two sulphur -2,5- bis- of Isosorbide-5-Nitrae
The molar ratio of pure and mild 1,1,3,3- tetramethoxy propane is 1 ﹕ (2-4).
8. the preparation method of 3- thiophenecarboxaldehyde according to claim 1, which is characterized in that described 1,1,3,3- tetramethoxy
The molar ratio of propane and acid is (2-4) ﹕ (0.2-0.4).
9. the preparation method of 3- thiophenecarboxaldehyde according to claim 1, which is characterized in that the acid is hydrochloric acid.
10. the preparation method of 3- thiophenecarboxaldehyde according to claim 9, which is characterized in that the mass fraction of the hydrochloric acid
For 8%-15%.
11. the preparation method of 3- thiophenecarboxaldehyde according to claim 1, which is characterized in that-two sulphur -2,5- bis- of Isosorbide-5-Nitrae
The molar ratio of alcohol and alkali is 1 ﹕ (0.5-1).
12. the preparation method of 3- thiophenecarboxaldehyde according to claim 1, which is characterized in that the method packet of the post-processing
It includes following steps: the mixture after reaction being added to the water and is quenched, organic solvent extraction is then added and separates organic phase, it is dense
Contracting obtains the 3- thiophenecarboxaldehyde.
13. the preparation method of 3- thiophenecarboxaldehyde according to claim 12, which is characterized in that the organic solvent includes second
One of acetoacetic ester, toluene and isohexane are a variety of.
14. the preparation method of 3- thiophenecarboxaldehyde according to claim 12 or 13, which is characterized in that the organic solvent with
The mass ratio of bis- sulphur -2,5- glycol of 1,4- is (8-15) ﹕ 1.
15. the preparation method of 3- thiophenecarboxaldehyde according to claim 12, which is characterized in that add the mixture after reaction
Enter in cold water and is quenched.
16. the preparation method of 3- thiophenecarboxaldehyde according to claim 15, which is characterized in that the temperature of the cold water is 3-
12℃。
17. the preparation method of 3- thiophenecarboxaldehyde according to claim 16, which is characterized in that the temperature of the cold water is 5-
10℃。
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| JP2001199979A (en) * | 2000-01-19 | 2001-07-24 | Ube Ind Ltd | Method for producing thiophene-3-carboxaldehyde |
| WO2001083489A1 (en) * | 2000-05-04 | 2001-11-08 | Astrazeneca Ab | THIENO[2,3-d]PYRIMIDINEDIONES AND THEIR USE AS PHARMACEUTICALS |
| CN101175746A (en) * | 2005-05-16 | 2008-05-07 | 宇部兴产株式会社 | Process for producing 3-substituted thiophene |
-
2017
- 2017-12-26 CN CN201711433755.0A patent/CN107935984B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001199979A (en) * | 2000-01-19 | 2001-07-24 | Ube Ind Ltd | Method for producing thiophene-3-carboxaldehyde |
| WO2001083489A1 (en) * | 2000-05-04 | 2001-11-08 | Astrazeneca Ab | THIENO[2,3-d]PYRIMIDINEDIONES AND THEIR USE AS PHARMACEUTICALS |
| CN101175746A (en) * | 2005-05-16 | 2008-05-07 | 宇部兴产株式会社 | Process for producing 3-substituted thiophene |
Non-Patent Citations (2)
| Title |
|---|
| "A SHORT, PRACTICAL SYNTHESIS OF 3-THIOPHENECARBOXALDEHYDE";Brian K. Huckabee等;《Synthetic Communications》;20100802;第31卷(第10期);第1527-1530页 |
| "Facile synthesis of 3-aldehyde-2-substituted thiophenes through Lewis base catalyzed [3+2] cycloaddition of 1,4-dithiane-2,5-diolswith ynals";Shi Wenjuan等;《Tetrahedron Letters》;20150317;第56卷;第2083-2085页 |
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