CN107935984A - A kind of preparation method of 3 thiophenecarboxaldehyde - Google Patents
A kind of preparation method of 3 thiophenecarboxaldehyde Download PDFInfo
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- 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
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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 3 thiophenecarboxaldehyde, includes the following steps：After 1,1,3,3 tetramethoxy propane is reacted under acid condition, hybrid reaction, post processing obtain 3 thiophenecarboxaldehydes in alkaline conditions with two sulphur of Isosorbide-5-Nitrae, 2,5 glycol.The preparation method of 3 thiophenecarboxaldehydes of the present invention is only by being simply mixed reaction, you can 3 thiophenecarboxaldehyde products of the purity more than 98% are prepared, is reacted in preparation process without ultralow temperature and using hazardous agents, improves production safety coefficient.And the preparation method of the present invention is easy to operate, and raw material is easy to get, and has saved running cost and cost of material, suitable for 3 thiophenecarboxaldehyde of industrialized production.
Description
Technical field
The present invention relates to technical field of organic synthesis, more particularly, to a kind of preparation method of 3- thiophenecarboxaldehydes.
Background technology
3- thiophenecarboxaldehydes are a kind of colourless or weak yellow liquids, and solution colour gradually deepens after meeting light, has irritation gas
Taste, is soluble in the organic solvents such as alcohol, benzene, ether, dichloromethane, is slightly soluble in water.3- thiophenecarboxaldehydes are in a kind of important medicine
Mesosome, is mainly used for amine antimicrobial antiphlogistic, 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- thiophenecarboxaldehydes is, with the sulphur -2,5- of Isosorbide-5-Nitrae-two glycol for raw material, first synthesizes 2,5- dihydro -3- thiophenecarboxaldehydes,
3- thiophenecarboxaldehydes are 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 to react under extremely low temperature conditionss, once temperature is slightly higher easily to produce impurity, it is harsh to equipment requirement, it is necessary to
Special Cryo Equipment, energy consumption is larger, is not easy to amplify.Also document (Bulletin of the Korean Chemical
Society, 2013,34 (4), 1170-1174) report, using 3 bromo thiophene as raw material, reacts at -78 DEG C with n-BuLi
The temperature needed to 3- thiophenecarboxaldehydes, this route and its low, unsuitable industrialization, also, n-BuLi meets the poles such as water, oxide
Easy burn, easily catches fire, and uses danger close.
In view of this, it is special to propose the present invention.
The content of the invention
It is easy to operate it is an object of the invention to provide a kind of preparation method suitable for industrialized production 3- thiophenecarboxaldehydes
Economy, high income, purity are high, and to solve extremely low reaction temperature existing in the prior art, reagent safety is low and is not easy
The technical problem of amplification.
In order to realize the above-mentioned purpose of the present invention, spy uses following technical scheme：
A kind of preparation method of 3- thiophenecarboxaldehydes, includes the following steps：
After 1,1,3,3- tetramethoxy propane is reacted under acid condition, with the sulphur -2,5- of Isosorbide-5-Nitrae-two glycol in alkaline bar
Hybrid reaction under part, post processing obtain 3- thiophenecarboxaldehydes.
The preparation method of the 3- thiophenecarboxaldehydes of the present invention is only by being simply mixed reaction, you can purity is prepared
3- thiophenecarboxaldehyde products more than 98%, and reacted without ultralow temperature in preparation process and using hazardous agents, improve life
Produce safety coefficient.And the preparation method of the present invention is easy to operate, and raw material is easy to get, and has saved running cost and cost of material, fit
For industrialized production 3- thiophenecarboxaldehydes.
1,1,3,3- tetramethoxy propane under the action of an acid, can react generation malonaldehyde at room temperature, be produced in centre
Sulphur -2, the 5- glycol of Isosorbide-5-Nitrae-two is directly added into thing malonaldehyde, under the action of alkali, reaction generation 3- thiophenecarboxaldehydes.
1,1,3,3- tetramethoxy propane and sulphur -2, the 5- diol starting materials of Isosorbide-5-Nitrae-two be easy to get and safety, and reaction process without
Ultralow temperature or superhigh temperature are needed, production safety coefficient, and catalyst without costliness etc. is improved, both reduces cost of material,
It turn avoid the problem of catalyst is not easy to remove in last handling process.
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 propanes under acid condition is 2-3h.
Preferably, the reaction temperature with the sulphur -2,5- of Isosorbide-5-Nitrae-two glycol in alkaline conditions is 50-70 DEG C.It is furthermore preferred that with
The reaction time of bis- sulphur -2,5- glycol of 1,4- in alkaline conditions is 4-6h.
Preferably, the sulphur -2,5- of Isosorbide-5-Nitrae-two glycol and 1, the molar ratio of 1,3,3- tetramethoxy propane is 1 ﹕ (1.5-
5).It is furthermore preferred that the sulphur -2,5- of Isosorbide-5-Nitrae-two glycol and 1, 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 or more in acid and sulfonic acid.
Preferably, described 1, the molar ratio of 1,3,3- tetramethoxy propane and acid is (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, the alkali with the sulphur -2,5- of Isosorbide-5-Nitrae-two glycol hybrid reaction in alkaline conditions is organic base.It is furthermore preferred that
The organic base includes the one or more in diethylamine, triethylamine, piperidines, pyridine and DBU.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：Mixture after reaction is added to the water and is quenched,
Then add organic solvent extraction and separate organic phase, be concentrated to give the 3- thiophenecarboxaldehydes.
Preferably, the organic solvent includes the one or more in ethyl acetate, toluene and isohexane.
The mixture for reacting the obtained thiophenecarboxaldehyde containing 3- is added in cold water mode is quenched, reduce accessory substance
Generation, selects model, substantially increases product yield and purity.
Preferably, the mass ratio of the organic solvent and sulphur -2, the 5- glycol of Isosorbide-5-Nitrae-two is (8-15) ﹕ 1.
By selecting suitable extraction split-phase solvent, product of the purity more than 98% can be obtained, 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, beneficial effects of the present invention are：
(1) preparation method of the invention is only by being simply mixed reaction, you can purity is prepared more than 98%
3- thiophenecarboxaldehydes, and the high income of 3- thiophenecarboxaldehydes；
(2) preparation method of the invention is easy to operate without being reacted under condition of ultralow temperature, without Cryo Equipment, saves
Running cost and energy consumption；
(3) preparation method of the invention is used as former using bis- sulphur -2,5- glycol of 1,4- and 1,1,3,3- tetramethoxy propanes
Material, raw material are easy to get, it is not necessary to which hazardous agents, effectively increase production safety coefficient；
(4) preparation method simple economy of the invention, suitable for industrialized production 3- thiophenecarboxaldehydes.
Brief description of the drawings
, below will be to specific in order to illustrate more clearly of the specific embodiment of the invention or technical solution of the prior art
Embodiment or attached drawing needed to be used in the description of the prior art are briefly described, it should be apparent that, in describing below
Attached drawing is some embodiments of the present invention, for those of ordinary skill in the art, before not making the creative labor
Put, other attached drawings can also be obtained according to these attached drawings.
Fig. 1 is the gas chromatogram for the 3- thiophenecarboxaldehydes that the embodiment of the present invention 1 is prepared；
Fig. 2 is the gas chromatogram for the 3- thiophenecarboxaldehydes that the embodiment of the present invention 2 is prepared；
Fig. 3 is the gas chromatogram for the 3- thiophenecarboxaldehydes that the embodiment of the present invention 3 is prepared；
Fig. 4 is the gas chromatogram for the 3- thiophenecarboxaldehydes that the embodiment of the present invention 4 is prepared.
Embodiment
Technical scheme 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 following described embodiment is part of the embodiment of the present invention, it is rather than 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 all other embodiments obtained without making creative work, belong to guarantor of the present invention
The scope of shield.The person that is not specified actual conditions in embodiment, the condition suggested according to normal condition or manufacturer carry out.Agents useful for same
It is the conventional products that can be obtained by commercially available purchase or production firm person is not specified in instrument.
The preparation method of the 3- thiophenecarboxaldehydes of the present invention, includes the following steps：
(a) acid is added to 1,1,3,3- tetramethoxy propane under agitation, controlling reaction temperature is 20-40 DEG C, is stirred
Mix reaction 2-3h；
(b) add the sulphur -2,5- of Isosorbide-5-Nitrae-two glycol in the mixture obtained into step (a) and alkali, controlling reaction temperature are
50-70 DEG C, 4-6h is reacted, obtains 3- thiophenecarboxaldehyde solution；
(c) 3- thiophenecarboxaldehydes solution is post-processed, obtains 3- thiophenecarboxaldehydes；Specifically, 3- thiophenecarboxaldehydes solution is added
It is quenched in water, then adds organic solvent extraction and separate organic phase, wash organic phase, be concentrated to give the 3- thiophene first
Aldehyde.
Wherein, the sulphur -2,5- of Isosorbide-5-Nitrae-two glycol, 1,1,3,3- tetramethoxy propane, acid, the molar ratio of alkali are preferably 1 ﹕
(2-4) ﹕ (0.2-0.4) ﹕ (0.5-1).In this proportion, it can ensure the yield of 3- thiophenecarboxaldehydes being prepared
Height, and purity is good, and the utilization rate of raw material maximizes, production cost is relatively minimum.
The acid is preferably the one or more in hydrochloric acid, sulfuric acid, p-methyl benzenesulfonic acid and sulfonic acid.
The alkali is preferably in diethylamine, triethylamine, piperidines, pyridine and DBU (11 carbon -7- alkene of 1,8- diazabicylos)
One or more.
In post processing, the organic solvent is preferably the one or more in ethyl acetate, toluene and isohexane.
The synthetic route of the 3- thiophenecarboxaldehydes of the present invention is as follows：
1,1,3,3- tetramethoxy propane under the action of an acid, can react generation malonaldehyde at room temperature, be produced in centre
Sulphur -2, the 5- glycol of Isosorbide-5-Nitrae-two is directly added into thing malonaldehyde, under the action of alkali, reaction generation 3- thiophenecarboxaldehydes.
Embodiment 1
The preparation method of the 3- thiophenecarboxaldehydes 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 material of the HCl in the hydrochloric acid of addition, following embodiments to the hydrochloric acid that 0.2mol mass fractions are 10%
Similarly), it is 20 DEG C by reaction temperature control, stirring reaction 2h.
(b) in the mixture in the reaction vessel into step (a) add 1mol bis- sulphur -2,5- glycol of 1,4- and
The triethylamine of 0.5mol, is 60 DEG C by reaction temperature control, and stirring reaction 4h, obtains 3- thiophenecarboxaldehyde solution.
(c) the 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 extraction split-phase is added into system, collects organic phase；Add water into organic phase to be washed, then split-phase
Collect organic phase；Organic phase is concentrated, removes excessive raw material and solvent, obtains 3- thiophenecarboxaldehyde products, yield 62%.Its
In, the addition for the ethyl acetate of extraction is 8 times of the quality of sulphur -2, the 5- glycol of Isosorbide-5-Nitrae-two, for washing organic phase
The addition of water is 4 times of the quality of bis- sulphur -2,5- glycol of 1,4-.Referring to Fig. 1, its 3- thiophene that to be the present embodiment be prepared
The gas chromatogram of fen formaldehyde, it can be seen that the purity for the 3- thiophenecarboxaldehyde products that the present embodiment is prepared is
98.97%.
Embodiment 2
The preparation method of the 3- thiophenecarboxaldehydes 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
0.2mol mass fractions are 8% hydrochloric acid, are 25 DEG C by reaction temperature control, stirring reaction 3h.
(b) in the mixture in the reaction vessel into step (a) add 1mol bis- sulphur -2,5- glycol of 1,4- and
The diethylamine of 0.7mol, is 70 DEG C by reaction temperature control, and stirring reaction 4h, obtains 3- thiophenecarboxaldehyde solution.
(c) the 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 extraction split-phase is added into system, collects organic phase；Add water into organic phase to be washed, then split-phase is collected
Organic phase；Organic phase is concentrated, removes excessive raw material and solvent, obtains 3- thiophenecarboxaldehyde products, yield 64%.Wherein,
Addition for the toluene of extraction is 8 times of the quality of sulphur -2, the 5- glycol of Isosorbide-5-Nitrae-two, the addition of the water for washing organic phase
Measure the quality for bis- sulphur -2,5- glycol of 1,4- 4 times.Referring to Fig. 2, its 3- thiophenecarboxaldehyde that to be the present embodiment be prepared
Gas chromatogram, it can be seen that the purity for the 3- thiophenecarboxaldehyde products that the present embodiment is prepared is 98.98%.
Embodiment 3
The preparation method of the 3- thiophenecarboxaldehydes 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
The mass fraction of 0.3mol is 15% hydrochloric acid, is 30 DEG C by reaction temperature control, stirring reaction 2.5h.
(b) the bis- sulphur -2,5- glycol of 1,4- and 1mol of 1mol is added in the mixture in the reaction vessel into step (a)
Piperidines, by reaction temperature control be 50 DEG C, stirring reaction 5h, obtain 3- thiophenecarboxaldehyde solution.
(c) the 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 extraction split-phase is added into system, collects organic phase；Add water into organic phase to be washed, then split-phase is received
Collect organic phase；Organic phase is concentrated, removes excessive raw material and solvent, obtains 3- thiophenecarboxaldehyde products, yield 60%.Its
In, the addition for the isohexane of extraction is 12 times of the quality of sulphur -2, the 5- glycol of Isosorbide-5-Nitrae-two, for washing the water of organic phase
Addition be 6 times of quality of bis- sulphur -2,5- glycol of 1,4-.Referring to Fig. 3, its 3- thiophene that to be the present embodiment be prepared
The gas chromatogram of formaldehyde, it can be seen that the purity for the 3- thiophenecarboxaldehyde products that the present embodiment is prepared is 98.77%.
Embodiment 4
The preparation method of the 3- thiophenecarboxaldehydes 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
0.4mol mass fractions are 12% hydrochloric acid, are 40 DEG C by reaction temperature control, stirring reaction 2h.
(b) in the mixture in the reaction vessel into step (a) add 1mol bis- sulphur -2,5- glycol of 1,4- and
The diethylamine of 0.8mol, is 70 DEG C by reaction temperature control, and stirring reaction 6h, obtains 3- thiophenecarboxaldehyde solution.
(c) the 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 extraction split-phase is added into system, collects organic phase；Add water into organic phase to be washed, then split-phase is received
Collect organic phase；Organic phase is concentrated, removes excessive raw material and solvent, obtains 3- thiophenecarboxaldehyde products, yield 65%.Its
In, the addition for the isohexane of extraction is 15 times of the quality of sulphur -2, the 5- glycol of Isosorbide-5-Nitrae-two, for washing the water of organic phase
Addition be 7 times of quality of bis- sulphur -2,5- glycol of 1,4-.Referring to Fig. 4, its 3- thiophene that to be the present embodiment be prepared
The gas chromatogram of formaldehyde, it can be seen that the purity for the 3- thiophenecarboxaldehyde products that the present embodiment is prepared is 98.62%.
Embodiment 5
Preparation method with reference to described in embodiment 4 prepares 3- thiophenecarboxaldehydes, differs only in, sulphur -2, the 5- glycol of Isosorbide-5-Nitrae-two
Molar ratio with 1,1,3,3- tetramethoxy propanes is 1 ﹕ 1.5.Characterized by identical gas chromatographic analysis, prepared by the present embodiment
The purity of obtained 3- thiophenecarboxaldehyde products is 98.64%.
Embodiment 6
Preparation method with reference to described in embodiment 4 prepares 3- thiophenecarboxaldehydes, differs only in, sulphur -2, the 5- glycol of Isosorbide-5-Nitrae-two
Molar ratio with 1,1,3,3- tetramethoxy propanes is 1 ﹕ 5.Characterized by identical gas chromatographic analysis, the present embodiment is prepared into
The purity of the 3- thiophenecarboxaldehyde products arrived is 98.60%.
Embodiment 7
Preparation method with reference to described in embodiment 4 prepares 3- thiophenecarboxaldehydes, differs only in, the acid is sulfuric acid, described
The mass fraction of sulfuric acid is 15%.Characterized by identical gas chromatographic analysis, the 3- thiophenecarboxaldehydes that the present embodiment is prepared
The purity of product is 98.73%.
Embodiment 8
Preparation method with reference to described in embodiment 4 prepares 3- thiophenecarboxaldehydes, differs only in, and the acid is to toluene sulphur
Acid.Characterized by identical gas chromatographic analysis, the purity for the 3- thiophenecarboxaldehyde products that the present embodiment is prepared is
98.66%.
Embodiment 9
Preparation method with reference to described in embodiment 4 prepares 3- thiophenecarboxaldehydes, differs only in, the acid is benzene sulfonic acid.It is logical
Identical gas chromatographic analysis characterization is crossed, the purity for the 3- thiophenecarboxaldehyde products that the present embodiment is prepared is 98.68%.
Embodiment 10
Preparation method with reference to described in embodiment 4 prepares 3- thiophenecarboxaldehydes, differs only in, and the temperature of the cold water is 3
℃.Characterized by identical gas chromatographic analysis, the purity for the 3- thiophenecarboxaldehyde products that the present embodiment is prepared is
98.78%.
Embodiment 11
Preparation method with reference to described in embodiment 4 prepares 3- thiophenecarboxaldehydes, differs only in, and the temperature of the cold water is 12
℃.Characterized by identical gas chromatographic analysis, the purity for the 3- thiophenecarboxaldehyde products that the present embodiment is prepared is
98.60%.
Comparative example 1
2,5- dihydro -3- thiophenecarboxaldehydes are first synthesized for raw material with the sulphur -2,5- of Isosorbide-5-Nitrae-two glycol, then with chlorosulfuric acid at -35 DEG C
Under conditions of synthesize 3- thiophenecarboxaldehydes.
Comparative example 2
Using 3 bromo thiophene as raw material, at -78 DEG C and n-BuLi reacts to obtain 3- thiophenecarboxaldehydes.
Experimental example 1
For the preparation method of the 3- thiophenecarboxaldehydes described in comparative illustration various embodiments of the present invention and the 3- of comparative example 1 and 2
The carry out such as the preparation method of thiophenecarboxaldehyde, raw material and reaction condition and yield to various embodiments of the present invention and comparative example 1 and 2 is total
Knot, is shown in Table 1.
Raw material, reaction condition and the yield of the different preparation methods of table 1
It was found from from upper table, raw material is easy to get used by the preparation method of 3- thiophenecarboxaldehydes of the invention, and cost of material is low,
Safety coefficient is high, and reaction condition is simple, without complex conditions such as superhigh temperature or low temperature, the yield of obtained 3- thiophenecarboxaldehydes
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 is described in detail the present invention with reference to foregoing embodiments, it will be understood by those of ordinary skill in the art that：Its according to
Can so modify to the technical solution described in foregoing embodiments, either to which part or all technical characteristic into
Row equivalent substitution；And these modifications or replacement, the essence of appropriate technical solution is departed from various embodiments of the present invention technology
The scope of scheme.
Claims (10)
1. a kind of preparation method of 3- thiophenecarboxaldehydes, it is characterised in that include the following steps：
After 1,1,3,3- tetramethoxy propane is reacted under acid condition, with the sulphur -2,5- of Isosorbide-5-Nitrae-two glycol in alkaline conditions
Hybrid reaction, post processing obtain 3- thiophenecarboxaldehydes.
2. the preparation method of 3- thiophenecarboxaldehydes according to claim 1, it is characterised in that 1,1,3,3- tetramethoxy propane
Reaction temperature under acid condition is 20-40 DEG C；
Preferably, 1, reaction time of 1,3, the 3- tetramethoxy propane under acid condition is 2-3h.
3. the preparation method of 3- thiophenecarboxaldehydes according to claim 1, it is characterised in that with sulphur -2, the 5- glycol of Isosorbide-5-Nitrae-two
Reaction temperature in alkaline conditions is 50-70 DEG C；
Preferably, the reaction time with the sulphur -2,5- of Isosorbide-5-Nitrae-two glycol in alkaline conditions is 4-6h.
4. the preparation method of 3- thiophenecarboxaldehydes according to claim 1, it is characterised in that the sulphur -2,5- of Isosorbide-5-Nitrae-two bis-
The molar ratio of alcohol and 1,1,3,3- tetramethoxy propanes is 1 ﹕ (1.5-5)；
Preferably, the sulphur -2,5- of Isosorbide-5-Nitrae-two glycol and 1, the molar ratio of 1,3,3- tetramethoxy propane is 1 ﹕ (2-4).
5. the preparation method of 3- thiophenecarboxaldehydes according to claim 1, it is characterised in that 1,1,3,3- tetramethoxy propane
The acid reacted under acid condition includes the one or more in hydrochloric acid, sulfuric acid, p-methyl benzenesulfonic acid and sulfonic acid；
Preferably, described 1, the molar ratio of 1,3,3- tetramethoxy propane and acid is (2-4) ﹕ (0.2-0.4)；
It is furthermore preferred that the acid is hydrochloric acid；
It is furthermore preferred that the mass fraction of the hydrochloric acid is 8%-15%.
6. the preparation method of 3- thiophenecarboxaldehydes according to claim 1, it is characterised in that with sulphur -2, the 5- glycol of Isosorbide-5-Nitrae-two
The alkali of hybrid reaction is organic base in alkaline conditions；
Preferably, the organic base includes the one or more in diethylamine, triethylamine, piperidines, pyridine and DBU；
Preferably, the molar ratio of the sulphur -2,5- of Isosorbide-5-Nitrae-two glycol and alkali is 1 ﹕ (0.5-1).
7. the preparation method of 3- thiophenecarboxaldehydes according to claim 1, it is characterised in that the method for the post processing includes
Following steps：Mixture after reaction is added to the water and is quenched, organic solvent extraction is then added and separates organic phase, concentrate
Obtain the 3- thiophenecarboxaldehydes.
8. the preparation method of 3- thiophenecarboxaldehydes according to claim 7, it is characterised in that the organic solvent includes acetic acid
One or more in ethyl ester, toluene and isohexane.
9. the preparation method of the 3- thiophenecarboxaldehydes according to claim 7 or 8, it is characterised in that the organic solvent and 1,
The mass ratio of bis- sulphur -2,5- glycol of 4- is (8-15) ﹕ 1；
Preferably, the mass ratio of the organic solvent and sulphur -2, the 5- glycol of Isosorbide-5-Nitrae-two is 8 ﹕ 1,12 ﹕ 1,15 ﹕ 1.
10. the preparation method of 3- thiophenecarboxaldehydes according to claim 7, it is characterised in that add the mixture after reaction
Enter in cold water and be quenched；
Preferably, the temperature of the cold water is 3-12 DEG C；
It is furthermore preferred that the temperature of the cold water is 5-10 DEG C.
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Citations (3)
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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 |
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2017
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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 |
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| Title |
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| BRIAN K. HUCKABEE等: ""A SHORT, PRACTICAL SYNTHESIS OF 3-THIOPHENECARBOXALDEHYDE"", 《SYNTHETIC COMMUNICATIONS》 * |
| SHI WENJUAN等: ""Facile synthesis of 3-aldehyde-2-substituted thiophenes through Lewis base catalyzed [3+2] cycloaddition of 1,4-dithiane-2,5-diolswith ynals"", 《TETRAHEDRON LETTERS》 * |
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