CN109305946A - A kind of synthetic method of 4- methyl -5- ethyoxyl oxazole - Google Patents
A kind of synthetic method of 4- methyl -5- ethyoxyl oxazole Download PDFInfo
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- CN109305946A CN109305946A CN201811451600.4A CN201811451600A CN109305946A CN 109305946 A CN109305946 A CN 109305946A CN 201811451600 A CN201811451600 A CN 201811451600A CN 109305946 A CN109305946 A CN 109305946A
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- oxazole
- ethyoxyl
- ethyoxyl oxazole
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- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 title claims abstract description 95
- 238000010189 synthetic method Methods 0.000 title claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims abstract description 185
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 99
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims abstract description 92
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 87
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 54
- -1 oxalyl alanine ethyl ester Chemical compound 0.000 claims abstract description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 42
- 238000003916 acid precipitation Methods 0.000 claims abstract description 32
- 239000011541 reaction mixture Substances 0.000 claims abstract description 30
- 239000000376 reactant Substances 0.000 claims abstract description 29
- 239000007788 liquid Substances 0.000 claims abstract description 26
- 238000007127 saponification reaction Methods 0.000 claims abstract description 25
- 238000010438 heat treatment Methods 0.000 claims abstract description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000007864 aqueous solution Substances 0.000 claims abstract description 13
- 239000003513 alkali Substances 0.000 claims abstract description 9
- 238000006386 neutralization reaction Methods 0.000 claims abstract description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 48
- 239000000047 product Substances 0.000 claims description 39
- 239000012074 organic phase Substances 0.000 claims description 26
- 239000007795 chemical reaction product Substances 0.000 claims description 19
- 230000035484 reaction time Effects 0.000 claims description 19
- 238000003756 stirring Methods 0.000 claims description 13
- 238000000034 method Methods 0.000 abstract description 26
- 230000008569 process Effects 0.000 abstract description 16
- 239000002351 wastewater Substances 0.000 abstract description 16
- 238000003786 synthesis reaction Methods 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 4
- 238000005516 engineering process Methods 0.000 abstract description 4
- 239000002253 acid Substances 0.000 description 26
- 238000009413 insulation Methods 0.000 description 16
- 239000000243 solution Substances 0.000 description 15
- 238000004821 distillation Methods 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 13
- 239000002904 solvent Substances 0.000 description 12
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 229910052708 sodium Inorganic materials 0.000 description 10
- 238000001256 steam distillation Methods 0.000 description 8
- 238000013517 stratification Methods 0.000 description 8
- 239000007789 gas Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 5
- 239000002585 base Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 230000008901 benefit Effects 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 238000005265 energy consumption Methods 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000002910 solid waste Substances 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- AFCIMSXHQSIHQW-UHFFFAOYSA-N [O].[P] Chemical compound [O].[P] AFCIMSXHQSIHQW-UHFFFAOYSA-N 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 150000003851 azoles Chemical class 0.000 description 2
- 238000006114 decarboxylation reaction Methods 0.000 description 2
- 239000012024 dehydrating agents Substances 0.000 description 2
- WVPKAWVFTPWPDB-UHFFFAOYSA-N dichlorophosphinic acid Chemical compound OP(Cl)(Cl)=O WVPKAWVFTPWPDB-UHFFFAOYSA-N 0.000 description 2
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 125000003504 2-oxazolinyl group Chemical class O1C(=NCC1)* 0.000 description 1
- MAOYFMLUTBSVFC-QMMMGPOBSA-N C(C)OC([C@@H](NCCC)CCO)=O Chemical compound C(C)OC([C@@H](NCCC)CCO)=O MAOYFMLUTBSVFC-QMMMGPOBSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- ROBXZHNBBCHEIQ-BYPYZUCNSA-N ethyl (2s)-2-aminopropanoate Chemical compound CCOC(=O)[C@H](C)N ROBXZHNBBCHEIQ-BYPYZUCNSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000011344 liquid material Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000003431 oxalo group Chemical group 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/34—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/36—One oxygen atom
- C07D263/42—One oxygen atom attached in position 5
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The present invention discloses a kind of synthetic method of 4- methyl -5- ethyoxyl oxazole, comprising the following steps: toluene, N- ethoxy oxalyl alanine ethyl ester, triethylamine and phosphorus oxychloride is sequentially added into reaction kettle, then heating carries out cyclization reaction；Water and liquid alkaline are added into the product of the cyclization reaction to pH value in saponification is carried out after alkalinity, collects lower layer's reactant after being then layered the saponification product；The aqueous solution of hydrochloric acid is added into lower layer's reactant to being in carry out heating reaction after acidity, so that lower layer's reactant is successively passed through acid precipitation reaction and decarboxylic reaction, obtains generating the reaction mixture for having 4- methyl -5- ethyoxyl oxazole；The reaction mixture is separated and purified to after being in neutrality with alkali neutralization, 4- methyl -5- ethyoxyl oxazole is obtained.The synthesis technology of 4- methyl -5- ethyoxyl oxazole is optimized in the present invention, reduces the wastewater flow rate generated in technical process.
Description
Technical field
The present invention relates to technical field of organic synthesis, in particular to a kind of synthetic method of 4- methyl -5- ethyoxyl oxazole.
Background technique
5- alkoxy-substituted oxazoline acid esters compound is important intermediate in organic chemistry and pharmaceutical synthesis, answers
It is very extensive with range, wherein 4- methyl -5- ethyoxyl oxazole is one of the main intermediate for synthesizing vitamin B6, at present 4-
The production technology of methyl -5- ethyoxyl oxazole is usually using N- ethoxy oxalyl alanine ethyl ester as raw material, after cyclization reaction
It hydrolyzes again, acid out and decarboxylation, is made after 4- methyl -5- ethyoxyl oxazole using separating-purifying, target product can be obtained.So
And the wastewater flow rate generated in the technical process of existing production 4- methyl -5- ethyoxyl oxazole is larger, it is to be improved.
Summary of the invention
The main object of the present invention is to propose a kind of synthetic method of 4- methyl -5- ethyoxyl oxazole, it is intended to reduce 4- first
The wastewater flow rate generated in base -5- ethyoxyl oxazole synthesis process.
To achieve the above object, the present invention proposes a kind of synthetic method of 4- methyl -5- ethyoxyl oxazole, including following step
It is rapid:
Step S10, toluene, N- ethoxy oxalyl alanine ethyl ester, triethylamine and phosphorus oxychloride are sequentially added into reaction kettle,
Then heating carries out cyclization reaction；
Step S20, water and liquid alkaline are added into the product of the cyclization reaction to pH value in carrying out saponification after alkalinity,
Then lower layer's reactant is collected after being layered the saponification product；
Step S30, the aqueous solution of hydrochloric acid is added to lower layer's reactant to being in carry out acid precipitation reaction after acidity, then will
The product heating of the acid precipitation reaction carries out decarboxylic reaction, obtains generating the reaction mixture for having 4- methyl -5- ethyoxyl oxazole；
Step S40, it is separated and is purified to after being in neutrality with alkali neutralization by the reaction mixture, obtain 4- methyl -5- second
Oxygroup oxazole.
Preferably, in step slo:
The N- ethoxy oxalyl alanine ethyl ester, phosphorus oxychloride, the molar ratio of triethylamine and toluene are 1:(0.5~2): (2
~6): (5~10)；And/or
The reaction temperature of the cyclization reaction is 70~110 DEG C, and the reaction time is 2~10h.
Preferably, in step slo:
The N- ethoxy oxalyl alanine ethyl ester, phosphorus oxychloride, the molar ratio of triethylamine and toluene are 1:1:3:7；With/
Or,
The reaction temperature of the cyclization reaction is 85 DEG C, reaction time 7h.
Preferably, step S10 is specifically included:
After sequentially adding toluene, N- ethoxy oxalyl alanine ethyl ester and triethylamine into reaction kettle, under stirring to
Phosphorus oxychloride is at the uniform velocity added dropwise in the reaction kettle, then heating carries out cyclization reaction, and obtaining generating has 4- methyl -5- ethyoxyl evil
The cyclization reaction product of azoles ester；
Wherein, the dropping temperature of the phosphorus oxychloride is 40~70 DEG C, and time for adding is 0.5~2h.
Preferably, in step slo:
The dropping temperature of the phosphorus oxychloride is 55 DEG C, time for adding 1h.
Preferably, in step S20:
The reaction temperature of the saponification is 50~80 DEG C, and the reaction time is 1~5h；And/or
The pH value of the saponification system is 12~14.
Preferably, in step S20:
The reaction temperature of the saponification is 70 DEG C, reaction time 3h.
Preferably, in step s 30:
The pH value of the acid precipitation reaction system is 1~3；And/or
The reaction temperature of the decarboxylic reaction is 50~90 DEG C, and the reaction time is 1~3h.
Preferably, in step s 30:
The pH value of the acid precipitation reaction system is 1.5；And/or
The reaction temperature of the decarboxylic reaction is 60 DEG C, reaction time 2h.
Preferably, step S40 is specifically included:
The reaction mixture is distilled to after being in neutrality with alkali neutralization and collects distillate；
Organic phase is collected after being extracted with chloroform to the distillate；
The organic phase is distilled to remove chloroform therein, obtains 4- methyl -5- ethyoxyl oxazole.
In technical solution provided by the invention, with toluene, N- ethoxy oxalyl alanine ethyl ester, triethylamine and phosphorus oxychloride work
For reaction system, 4- methyl -5- ethyoxyl oxazole ester is generated by cyclization reaction, then generates 4- methyl-by saponification
5- ethyoxyl oxazole acid sodium, generates 4- methyl -5- ethyoxyl oxazole acid using acid precipitation reaction, generates 4- first by decarboxylic reaction
Base -5- ethyoxyl oxazole finally can be obtained 4- methyl -5- ethyoxyl oxazole product, the process phase by purification
Than the wastewater flow rate for greatly reducing generation in prior art.
Detailed description of the invention
In order to more clearly explain the embodiment of the invention or the technical proposal in the existing technology, to embodiment or will show below
There is attached drawing needed in technical description to be briefly described, it should be apparent that, the accompanying drawings in the following description is only this
Some embodiments of invention for those of ordinary skill in the art without creative efforts, can be with
Other relevant attached drawings are obtained according to these attached drawings.
Fig. 1 is the flow diagram of an embodiment of the synthetic method of 4- methyl -5- ethyoxyl oxazole provided by the invention；
Fig. 2 is the process signal of another embodiment of the synthetic method of 4- methyl -5- ethyoxyl oxazole provided by the invention
Figure.
The embodiments will be further described with reference to the accompanying drawings for the realization, the function and the advantages of the object of the present invention.
Specific embodiment
It in order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below will be in the embodiment of the present invention
Technical solution be clearly and completely described.The person that is not specified actual conditions in embodiment, according to normal conditions or manufacturer builds
The condition of view carries out.Reagents or instruments used without specified manufacturer is the conventional production that can be obtained by commercially available purchase
Product.
For the product yield for improving existing production 4- methyl -5- ethyoxyl oxazole technique, the present invention proposes a kind of 4- methyl -
The synthetic method of 5- ethyoxyl oxazole, using N- ethoxy oxalyl alanine ethyl ester/phosphorus oxychloride/triethylamine/toluene system, successively
By the processing step of cyclization, extracting, saponification, acid out, decarboxylation, neutralization and distillation, 4- methyl -5- ethyoxyl is successfully made and dislikes
Azoles, and reduce the wastewater flow rate generated in technical process, Fig. 1 show 4- methyl -5- ethyoxyl oxazole provided by the invention
One embodiment of synthetic method.Referring to Fig. 1, in the present embodiment, the synthetic method packet of the 4- methyl -5- ethyoxyl oxazole
Include following steps:
Step S10, toluene, N- ethoxy oxalyl alanine ethyl ester, triethylamine and phosphorus oxychloride are sequentially added into reaction kettle,
Then heating carries out cyclization reaction；
During the cyclization reaction, the N- ethoxy oxalyl alanine ethyl ester is in triethylamine/phosphorus oxychloride/triethylamine
Reaction generates 4- methyl -5- ethyoxyl oxazole ester, triethylamine hydrochloride and dichloro phosphoric acid, following (the following reactions of reaction equation in system
N- oxalyl object in formula is the N- ethoxy oxalyl alanine ethyl ester put into step S10, and the oxazole ester of generation is the 4-
Methyl -5- ethyoxyl oxazole ester, the reaction equation in following step S20 are identical):
The N- ethoxy oxalyl alanine ethyl ester is as the primary raw material for preparing 4- methyl -5- ethyoxyl oxazole, and described three
Ethamine, phosphorus oxychloride and toluene are as cyclization dehydrating agent, in the present embodiment, the adding proportion of each material are as follows: the N- ethoxy
Oxalyl alanine ethyl ester, phosphorus oxychloride, the molar ratio of triethylamine and toluene are 1:(0.5~2): (2~6): (5~10), herein
Under proportion, the triethylamine, phosphorus oxychloride and toluene can promote further amounts of N- ethoxy oxalyl alanine as cyclization dehydrating agent
Ethyl ester is converted into 4- methyl -5- ethyoxyl oxazole ester by cyclization reaction.Further, the N- ethoxy oxalyl alanine second
Ester, phosphorus oxychloride, the molar ratio of triethylamine and toluene are more preferably 1:1:3:7, in this way, can not only effectively promote N- ethoxy oxalyl
Alanine ethyl ester reacts completely is converted into 4- methyl -5- ethyoxyl oxazole ester, is also avoided that unnecessary wastage of material.
Under normal conditions, the cyclization reaction needs are performed under heating conditions, to accelerate reaction process, in the present embodiment
In, the cyclization reaction carries out under normal pressure, and reaction temperature is 70~110 DEG C, the reaction time is 2~10h, reacts item herein
Under part, the cyclization reaction can forward direction go on smoothly.Further, during the cyclization reaction, gas phase can be passed through
The modes such as tracking determine reaction process, and determine the reaction temperature more optimized and time, wherein the reaction of the cyclization reaction
Temperature is more preferably 85 DEG C, reaction time 7h, with this condition, the attainable higher reaction rate of cyclization reaction,
And energy consumption is lower, time-consuming shorter.Further, the cyclization reaction carries out in the reaction kettle for adding condenser, to return
Solvent is flowed, the loss of solvent is reduced.
The phosphorus oxychloride is a kind of colorless and transparent fuming liquids, with the N- ethoxy oxalyl alanine ethyl ester, three
Ethamine and toluene will appear exothermic phenomenon when mixing, in the present embodiment, by being eventually adding the phosphorus oxychloride to described
Cyclization reaction system, slow, addition at the uniform velocity is into the cyclization reaction system more preferably by way of dropwise addition, to reduce
Risk of exotherm when charging improves operational safety.It can carry out when specific implementation: be sequentially added into reaction kettle in the following manner
After toluene, N- ethoxy oxalyl alanine ethyl ester and triethylamine, trichlorine oxygen is at the uniform velocity added dropwise into the reaction kettle under stirring
Phosphorus, then heating carries out cyclization reaction, obtains generating the cyclization reaction product for having 4- methyl -5- ethyoxyl oxazole ester；Wherein, institute
The dropping temperature for stating phosphorus oxychloride is 40~70 DEG C, and time for adding is 0.5~2h, i.e., will be added with toluene, N- ethoxy oxalyl third
After the reaction kettle of propylhomoserin ethyl ester and triethylamine is warming up to 40~70 DEG C, under stirring, in 0.5~2h by the trichlorine oxygen
Phosphorus is all added in the reaction kettle.By the way that the phosphorus oxychloride has been added in the dropping temperature and time for adding
Finish, so that the heat release during charging is controllable, avoids the occurrence of slug accident, improve operational safety.Further, described
The dropwise addition condition of phosphorus oxychloride is more preferably: dropping temperature is 55 DEG C, time for adding 1h, i.e., will be added with toluene, N- ethoxy
After the reaction kettle of oxalyl alanine ethyl ester and triethylamine is warming up to 55 DEG C, under stirring, in 1h or so by the trichlorine oxygen
Phosphorus is all added in the reaction kettle.Wherein, realizing that the phosphorus oxychloride is at the uniform velocity added dropwise can be used the adjustable of this field routine
The device for saving liquid material drop rate is realized, such as dropping funel or silicone tube add the combination unit of peristaltic pump, wherein using drop
The operation of liquid funnel is relatively simple, can rate be easy to regulate and control, only need the phosphorus oxychloride being added to dropping liquid when specific operation
In funnel, the opening size of dropping funel piston is then adjusted, i.e., controllable drop rate makes the phosphorus oxychloride scheduled
It is at the uniform velocity added dropwise to and finishes in time.
Step S20, water and liquid alkaline are added into the product of the cyclization reaction to pH value in carrying out saponification after alkalinity,
Then lower layer's reactant is collected after being layered the saponification product；
During the saponification, the 4- methyl -5- ethyoxyl oxazole ester in the cyclization reaction product is in water/liquid
Reaction generates 4- methyl -5- ethyoxyl oxazole acid sodium, dichloro phosphoric acid and triethylamine in the cyclization reaction product in alkali systems
Reaction generates triethylamine hydrochloride and phosphoric acid in water/liquid alkaline system, and reaction equation is following, and (oxazole acid sodium is the 4- in reaction equation
Methyl -5- ethyoxyl oxazole acid sodium):
The saponification is usually also required to be performed under heating conditions, and in the present embodiment, is saponified described in step S20
The reaction temperature of reaction is 50~80 DEG C, and the reaction time is 1~5h；And/or the pH value of the saponification system be 12~
14, to after completion of the reaction, the product after the saponification be stood to water phase and organic phase layering, collection mainly contains 4-
Lower layer's reactant of methyl -5- ethyoxyl oxazole acid sodium, is then demultiplex out lower layer's reactant, to carry out the acid out of next step
And decarboxylic reaction.The reaction temperature and time conditions and pH value of reaction system condition of above-mentioned saponification can limit simultaneously,
A restriction can also be selected, in the present embodiment to limit simultaneously, to improve reaction efficiency.
Further, during the saponification, it again may be by tracking reaction process to optimize it and react item
Part, wherein the condition of saponification described in step S20 be more preferably reaction temperature be 70 DEG C, reaction time 3h, the soap
The pH value for changing reaction system is more preferably 14, and at this point in the reaction, the 4- methyl -5- ethyoxyl oxazole ester is able to sufficiently anti-
4- methyl -5- ethyoxyl oxazole acid sodium should be generated, and reaction temperature is lower, time-consuming shorter.
Step S30, the aqueous solution of hydrochloric acid is added to lower layer's reactant to being in carry out acid precipitation reaction after acidity, then will
The product heating of the acid precipitation reaction carries out decarboxylic reaction, obtains generating the reaction mixture for having 4- methyl -5- ethyoxyl oxazole；
4- first of the aqueous solution of hydrochloric acid to after being in acidity, in the saponification product is added to lower layer's reactant
Acid precipitation reaction occurs in acid solution environment for base -5- ethyoxyl oxazole acid sodium, corresponding to generate 4- methyl -5- ethyoxyl oxazole
Acid, reaction equation are following (oxazole acid is the 4- methyl -5- ethyoxyl oxazole acid in reaction equation):
4- methyl -5- ethyoxyl oxazole acid the sodium reacts in acid solution environment generates 4- methyl -5- ethyoxyl evil
After azoles acid, continuation heats in the acid solution environment and decarboxylic reaction occurs, and generates target product 4- first to remove carboxyl
Base -5- ethyoxyl oxazole, and carbon dioxide gas is released, reaction equation is following, and (oxazole is the 4- methyl -5- second in reaction equation
Oxygroup oxazole):
Since the process needs of 4- methyl -5- ethyoxyl oxazole acid removing carboxyl are performed under heating conditions,
The reaction temperature of the heating reaction can should at least make the 4- methyl -5- ethyoxyl oxazole acid smoothly remove carboxyl, at this
In embodiment, the pH value of the acid precipitation reaction system is 1~3 in step s 30；And/or the reaction temperature of the decarboxylic reaction
It is 1~3h for 50~90 DEG C, reaction time.The reaction temperature and time conditions of above-mentioned decarboxylic reaction and acid precipitation reaction system
PH value can limit simultaneously, can also select a restriction, in the present embodiment to limit simultaneously, to improve reaction efficiency.
Further, since the 4- methyl -5- ethyoxyl oxazole acid can release titanium dioxide during decarboxylic reaction
Carbon gas, therefore reaction process can be judged according to the production quantity of gas, to optimize reaction condition, wherein institute in step S30
State heating reaction reaction condition be more preferably reaction temperature be 60 DEG C, reaction time 2h；And/or the heating reactant
The pH value of system is 1.5, and with this condition, the 4- methyl -5- ethyoxyl oxazole acid sodium, which can sufficiently react, generates 4- methyl -5-
Ethyoxyl oxazole, and reaction efficiency is high, time-consuming shorter.
Step S40, it is separated and is purified to after being in neutrality with alkali neutralization by the reaction mixture, obtain 4- methyl -5- second
Oxygroup oxazole.
Obtain production have the reaction mixture of purpose product 4- methyl -5- ethyoxyl oxazole after, first plus alkali neutralization to solution is in
After neutrality, then separation and the purification of product are carried out, can be obtained 4- methyl -5- ethyoxyl oxazole product, wherein described point
It is carried out from conventional in the prior art separation and method of purification is referred to the step of purification, for example, being in neutrality to being neutralized to
Reaction mixture afterwards carries out the substance separation that distillation keeps its mid-boiling point different, then extracts to the distillate containing target product
Rear recycling extractant is taken, can be obtained purpose product.In another embodiment provided by the invention, purpose product is carried out
The method of separating-purifying can also carry out in the following manner, referring to Fig. 2, step S40 is specifically included:
Step S41, it is distilled to after being in neutrality with alkali neutralization by the reaction mixture and collects distillate；
Step S42, organic phase is collected after being extracted with chloroform to the distillate；
Step S43, the organic phase is distilled to remove chloroform therein, obtains 4- methyl -5- ethyoxyl oxazole.
The alkaline matters such as liquid alkaline are added into the reaction mixture, adjusting pH value is 6.5~7.5, then uses vapor
Distillate is distilled and collected, 4- methyl -5- ethyoxyl oxazole crude product is obtained；Then using chloroform as extractant, to 4- methyl -5-
Ethyoxyl oxazole crude product is extracted, and makes water phase and organic phase layering in the 4- methyl -5- ethyoxyl oxazole crude product, then
Collect organic phase；The extractant chloroform in the organic phase finally is removed again by distillation, and then the 4- after being purified
Methyl -5- ethyoxyl oxazole product.
The present invention is using toluene, N- ethoxy oxalyl alanine ethyl ester, triethylamine and phosphorus oxychloride as reaction system, by ring
It closes reaction and generates 4- methyl -5- ethyoxyl oxazole ester, then generate 4- methyl -5- ethyoxyl oxazole acid sodium by saponification,
4- methyl -5- ethyoxyl oxazole acid is generated using acid precipitation reaction, generates 4- methyl -5- ethyoxyl oxazole by decarboxylic reaction,
Finally it can be obtained 4- methyl -5- ethyoxyl oxazole product by purification, this synthetic method has the advantage that (1) originally
Technique reduces the discharge of waste water, exhaust gas and solid waste, is embodied in: compared in prior art, every production 1kg purpose product is about
24kg waste water is generated, this technique produces the waste water that same amount of purpose product only generates about 14kg or so, reduces discharge of wastewater
Amount about 40%, to save the runing time of effluent treatment plant about 40%；It extracted, washed by reduction, water, decompression is divided to steam
The number for the operational sequences such as evaporating reduces exhaust gas discharge；The cyclization reaction is reduced using condenser reflux solvent is added
The discharge of solvent loss and exhaust gas；It is generated in entire technical process without solid waste；(2) compared to existing production 4- methyl -5- second
The process of oxygroup oxazole improves product yield, and yield is up to 82.51~84.62%；(3) pass through cyclization reaction
The adjustment of material order of addition in journey, keeps exothermic heat of reaction controllable, is not in slug accident, improves operational safety；(4) right
Synthesis technology is simplified, and compared to prior art, from being dosed into, to obtain 4- methyl -5- ethyoxyl oxazole crude product time-consuming about 50h left
The right side, this technique only time-consuming 35h or so, accelerates reaction process, shortens reaction time；(6) technical process provided by the invention
Recycling triethylamine is not needed, and 4- methyl -5- ethyoxyl oxazole obtained needs not move through 150 DEG C of high temperature distillation processes, not only
Wastewater flow rate is advantageously reduced, and significantly reduces operation energy consumption, to reduce process costs, and is subtracted compared to prior art
The dosage about 25% for having lacked triethylamine, reduces cost of material.
Technical solution of the present invention is described in further detail below in conjunction with specific embodiments and the drawings, it should be understood that
Following embodiment is only used to explain the present invention, is not intended to limit the present invention.
Embodiment 1
(1) 13L (122.2mol) toluene, 4kg (18.41mol) are successively put into 50L reaction kettle (adding condenser)
N- ethoxy oxalyl alanine ethyl ester, 7.7L (55.4mol) triethylamine, above-mentioned solution is stirred, reaction kettle is then heated to
After interior temperature is 50 DEG C, 2.9kg (18.91mol) phosphorus oxychloride is added dropwise into reaction kettle, control drop rate makes phosphorus oxychloride
Time for adding is 1h, and 85 DEG C of insulation reaction 7h are heated to after being added dropwise, obtain cyclization reaction product；
(2) cyclization reaction product is cooled to 50 DEG C, 4L water is added and stirs 30min, liquid alkaline is then added and is adjusted to pH
Value is 14, then in 70 DEG C of insulation reaction 3h, stratification and collects lower layer's reactant after completion of the reaction；
(3) being adjusted to pH value to the aqueous solution (molar concentration of hydrochloric acid is 0.3mol/L) that hydrochloric acid is added in lower layer's reactant is
1.5, to carry out acid precipitation reaction, to acid precipitation reaction after be heated to 60 DEG C of progress decarboxylic reaction 2h, reaction to bubble-free generates
As reaction end obtains generating the reaction mixture for having 4- methyl -5- ethyoxyl oxazole；
(4) after being cooled to room temperature reaction mixture, it is 7 that liquid alkaline, which is added, and is adjusted to pH value, then using after steam distillation
Distillate is collected, then using chloroform as solvent, organic phase is collected after extracting to distillate, finally by distillation removal organic phase
In chloroform, obtain purpose product 4- methyl -5- ethyoxyl oxazole.
Embodiment 2
(1) 13.47L (126.6mol) toluene, 5.5kg are successively put into 50L reaction kettle (condenser is housed)
(25.32mol) N- ethoxy oxalyl alanine ethyl ester, 7.04L (50.64mol) triethylamine, above-mentioned solution are stirred, then
Be heated to reactor temperature be 40 DEG C after, into reaction kettle be added dropwise 1.94kg (12.66mol) phosphorus oxychloride, control be added dropwise speed
Rate makes the time for adding 2h of phosphorus oxychloride, and 70 DEG C of insulation reaction 10h are heated to after being added dropwise, obtain cyclization reaction product；
(2) cyclization reaction product is cooled to 50 DEG C, 4L water is added and stirs 30min, liquid alkaline is then added and is adjusted to pH
Value is 13, then in 50 DEG C of insulation reaction 5h, stratification and collects lower layer's reactant after completion of the reaction；
(3) being adjusted to pH value to the aqueous solution (molar concentration of hydrochloric acid is 0.3mol/L) that hydrochloric acid is added in lower layer's reactant is
1.0, to carry out acid precipitation reaction, to acid precipitation reaction after be heated to 50 DEG C of progress decarboxylic reaction 3h, reaction to bubble-free generates
As reaction end obtains generating the reaction mixture for having 4- methyl -5- ethyoxyl oxazole；
(4) after being cooled to room temperature reaction mixture, it is 7 that liquid alkaline, which is added, and is adjusted to pH value, then using after steam distillation
Distillate is collected, then using chloroform as solvent, organic phase is collected after extracting to distillate, finally by distillation removal organic phase
In chloroform, obtain purpose product 4- methyl -5- ethyoxyl oxazole.
Embodiment 3
(1) 17.63L (165.722mol) toluene, 6kg are successively put into 50L reaction kettle (condenser is housed)
(27.62mol) N- ethoxy oxalyl alanine ethyl ester, 11.52L (82.86mol) triethylamine, above-mentioned solution are stirred, then
Be heated to reactor temperature be 60 DEG C after, into reaction kettle be added dropwise 3.39kg (22.10mol) phosphorus oxychloride, control be added dropwise speed
Rate makes the time for adding 1.5h of phosphorus oxychloride, and 80 DEG C of insulation reaction 8h are heated to after being added dropwise, obtain cyclization reaction product；
(2) cyclization reaction product is cooled to 50 DEG C, 4L water is added and stirs 30min, liquid alkaline is then added and is adjusted to pH
Value is 12, then in 60 DEG C of insulation reaction 4h, stratification and collects lower layer's reactant after completion of the reaction；
(3) being adjusted to pH value to the aqueous solution (molar concentration of hydrochloric acid is 0.3mol/L) that hydrochloric acid is added in lower layer's reactant is
2.0, to carry out acid precipitation reaction, to acid precipitation reaction after be heated to 60 DEG C of progress decarboxylic reaction 2h, reaction to bubble-free generates
As reaction end obtains generating the reaction mixture for having 4- methyl -5- ethyoxyl oxazole；
(4) after being cooled to room temperature reaction mixture, it is 7 that liquid alkaline, which is added, and is adjusted to pH value, then using after steam distillation
Distillate is collected, then using chloroform as solvent, organic phase is collected after extracting to distillate, finally by distillation removal organic phase
In chloroform, obtain purpose product 4- methyl -5- ethyoxyl oxazole.
Embodiment 4
(1) 19.59L (184.1mol) toluene, 4kg are successively put into 50L reaction kettle (condenser is housed)
(18.41mol) N- ethoxy oxalyl alanine ethyl ester, 15.35L (11.46mol) triethylamine, above-mentioned solution are stirred, then
Be heated to reactor temperature be 70 DEG C after, into reaction kettle be added dropwise 5.64kg (36.82mol) phosphorus oxychloride, control be added dropwise speed
Rate makes the time for adding 0.5h of phosphorus oxychloride, and 90 DEG C of insulation reaction 6h are heated to after being added dropwise, obtain cyclization reaction product；
(2) cyclization reaction product is cooled to 50 DEG C, 4L water is added and stirs 30min, liquid alkaline is then added and is adjusted to pH
Value is 14, then in 65 DEG C of insulation reaction 1.5h, stratification and collects lower layer's reactant after completion of the reaction；
(3) being adjusted to pH value to the aqueous solution (molar concentration of hydrochloric acid is 0.3mol/L) that hydrochloric acid is added in lower layer's reactant is
1.5, to carry out acid precipitation reaction, to acid precipitation reaction after be heated to 65 DEG C of progress decarboxylic reaction 1.5h, reaction to bubble-free produces
Raw is reaction end, obtains generating the reaction mixture for having 4- methyl -5- ethyoxyl oxazole；
(4) after being cooled to room temperature reaction mixture, it is 7 that liquid alkaline, which is added, and is adjusted to pH value, then using after steam distillation
Distillate is collected, then using chloroform as solvent, organic phase is collected after extracting to distillate, finally by distillation removal organic phase
In chloroform, obtain purpose product 4- methyl -5- ethyoxyl oxazole.
Embodiment 5
(1) 13.71L (128.87mol) toluene, 4kg are successively put into 50L reaction kettle (condenser is housed)
(18.41mol) N- ethoxy oxalyl alanine ethyl ester, 7.68L (55.23mol) triethylamine, above-mentioned solution are stirred, then
Be heated to reactor temperature be 55 DEG C after, into reaction kettle be added dropwise 2.82kg (18.4mol) phosphorus oxychloride, control drop rate
The time for adding 1h for making phosphorus oxychloride is heated to 85 DEG C of insulation reaction 7h, obtains cyclization reaction product after being added dropwise；
(2) cyclization reaction product is cooled to 50 DEG C, 4L water is added and stirs 30min, liquid alkaline is then added and is adjusted to pH
Value is 14, then in 70 DEG C of insulation reaction 3h, stratification and collects lower layer's reactant after completion of the reaction；
(3) being adjusted to pH value to the aqueous solution (molar concentration of hydrochloric acid is 0.3mol/L) that hydrochloric acid is added in lower layer's reactant is
1.5, to carry out acid precipitation reaction, to acid precipitation reaction after be heated to 60 DEG C of progress decarboxylic reaction 2h, reaction to bubble-free generates
As reaction end obtains generating the reaction mixture for having 4- methyl -5- ethyoxyl oxazole；
(4) after being cooled to room temperature reaction mixture, it is 7 that liquid alkaline, which is added, and is adjusted to pH value, then using after steam distillation
Distillate is collected, then using chloroform as solvent, organic phase is collected after extracting to distillate, finally by distillation removal organic phase
In chloroform, obtain purpose product 4- methyl -5- ethyoxyl oxazole.
Embodiment 6
(1) 17.63L (165.69mol) toluene, 4kg are successively put into 50L reaction kettle (condenser is housed)
(18.41mol) N- ethoxy oxalyl alanine ethyl ester, 10.24L (73.64mol) triethylamine, above-mentioned solution are stirred, then
Be heated to reactor temperature be 45 DEG C after, into reaction kettle be added dropwise 3.39kg (22.09mol) phosphorus oxychloride, control be added dropwise speed
Rate makes the time for adding 1.25h of phosphorus oxychloride, and 95 DEG C of insulation reaction 5h are heated to after being added dropwise, and obtains cyclization reaction production
Object；
(2) cyclization reaction product is cooled to 50 DEG C, 4L water is added and stirs 30min, liquid alkaline is then added and is adjusted to pH
Value is 13, then in 75 DEG C of insulation reaction 2h, stratification and collects lower layer's reactant after completion of the reaction；
(3) being adjusted to pH value to the aqueous solution (molar concentration of hydrochloric acid is 0.3mol/L) that hydrochloric acid is added in lower layer's reactant is
3.0, to carry out acid precipitation reaction, to acid precipitation reaction after be heated to 70 DEG C of progress decarboxylic reaction 2h, reaction to bubble-free generates
As reaction end obtains generating the reaction mixture for having 4- methyl -5- ethyoxyl oxazole；
(4) after being cooled to room temperature reaction mixture, it is 7 that liquid alkaline, which is added, and is adjusted to pH value, then using after steam distillation
Distillate is collected, then using chloroform as solvent, organic phase is collected after extracting to distillate, finally by distillation removal organic phase
In chloroform, obtain purpose product 4- methyl -5- ethyoxyl oxazole.
Embodiment 7
(1) 15.67L (147.28mol) toluene, 4kg are successively put into 50L reaction kettle (condenser is housed)
(18.41mol) N- ethoxy oxalyl alanine ethyl ester, 12.79L (92.05mol) triethylamine, above-mentioned solution are stirred, then
Be heated to reactor temperature be 65 DEG C after, into reaction kettle be added dropwise 5.08kg (33.14mol) phosphorus oxychloride, control be added dropwise speed
Rate makes the time for adding 1.75h of phosphorus oxychloride, and 100 DEG C of insulation reaction 4h are heated to after being added dropwise, and obtains cyclization reaction production
Object；
(2) cyclization reaction product is cooled to 50 DEG C, 4L water is added and stirs 30min, liquid alkaline is then added and is adjusted to pH
Value is 12, then in 80 DEG C of insulation reaction 1h, stratification and collects lower layer's reactant after completion of the reaction；
(3) being adjusted to pH value to the aqueous solution (molar concentration of hydrochloric acid is 0.3mol/L) that hydrochloric acid is added in lower layer's reactant is
2.5, to carry out acid precipitation reaction, to acid precipitation reaction after be heated to 80 DEG C of progress decarboxylic reaction 1.5h, reaction to bubble-free produces
Raw is reaction end, obtains generating the reaction mixture for having 4- methyl -5- ethyoxyl oxazole；
(4) after being cooled to room temperature reaction mixture, it is 7 that liquid alkaline, which is added, and is adjusted to pH value, then using after steam distillation
Distillate is collected, then using chloroform as solvent, organic phase is collected after extracting to distillate, finally by distillation removal organic phase
In chloroform, obtain purpose product 4- methyl -5- ethyoxyl oxazole.
Embodiment 8
(1) 14.1L (132.55mol) toluene, 4kg are successively put into 50L reaction kettle (condenser is housed)
(18.41mol) N- ethoxy oxalyl alanine ethyl ester, 11.52L (82.85mol) triethylamine, above-mentioned solution are stirred, then
Be heated to reactor temperature be 55 DEG C after, into reaction kettle be added dropwise 4.24kg (27.62mol) phosphorus oxychloride, control be added dropwise speed
Rate makes the time for adding 1h of phosphorus oxychloride, and 110 DEG C of insulation reaction 2h are heated to after being added dropwise, obtain cyclization reaction product；
(2) cyclization reaction product is cooled to 50 DEG C, 4L water is added and stirs 30min, liquid alkaline is then added and is adjusted to pH
Value is 14, then in 55 DEG C of insulation reaction 5h, stratification and collects lower layer's reactant after completion of the reaction；
(3) being adjusted to pH value to the aqueous solution (molar concentration of hydrochloric acid is 0.3mol/L) that hydrochloric acid is added in lower layer's reactant is
1.5, to carry out acid precipitation reaction, to acid precipitation reaction after be heated to 90 DEG C of progress decarboxylic reaction 1h, reaction to bubble-free generates
As reaction end obtains generating the reaction mixture for having 4- methyl -5- ethyoxyl oxazole；
(4) after being cooled to room temperature reaction mixture, it is 7 that liquid alkaline, which is added, and is adjusted to pH value, then using after steam distillation
Distillate is collected, then using chloroform as solvent, organic phase is collected after extracting to distillate, finally by distillation removal organic phase
In chloroform, obtain purpose product 4- methyl -5- ethyoxyl oxazole.
Content, quality and the technique of the purpose product 4- methyl -5- ethyoxyl oxazole of above-described embodiment 1 to 8 are counted respectively
The wastewater flow rate generated in the process, the corresponding wastewater flow rate for calculating the 1 ton of purpose product production of product yield and every production, as a result such as following table
Shown in 1.
The wastewater flow rate generated in the content of purpose product, yield and technical process in each embodiment of table 1
By the statistical result in table 1 it is found that synthesizing 4- methyl -5- ethyoxyl oxazole using method provided in this embodiment,
For the 4- methyl -5- ethyoxyl oxazole of every production 1kg about generates waste water 24kg in compared with the prior art, the embodiment of the present invention
The waste water of middle generation only 13.7~14.5kg, reduces wastewater flow rate about 40%, and then alleviate the workload of effluent treatment plant,
The runing time for saving effluent treatment plant about 40% reduces process costs, and entire technical process is generated without solid waste；
In addition, the yield of 4- methyl -5- ethyoxyl oxazole is up to 82.51~84.62%, and technique is more simplified, also improves operation
Safety saves the usage amount of triethylamine, needs not move through 150 DEG C of high temperature distillation process, reduces process energy consumption.
The above is only a preferred embodiment of the present invention, is not intended to limit the scope of the invention, for this field
For technical staff, the invention may be variously modified and varied.All within the spirits and principles of the present invention, made any
Modification, equivalent replacement, improvement etc. should all be included within the scope of the present invention.
Claims (10)
1. a kind of synthetic method of 4- methyl -5- ethyoxyl oxazole, which comprises the following steps:
Step S10, toluene, N- ethoxy oxalyl alanine ethyl ester, triethylamine and phosphorus oxychloride are sequentially added into reaction kettle, then
Heating carries out cyclization reaction；
Step S20, water and liquid alkaline are added into the product of the cyclization reaction to pH value in saponification is carried out after alkalinity, then
Lower layer's reactant is collected after being layered the saponification product；
Step S30, the aqueous solution of hydrochloric acid is added to lower layer's reactant to being in carry out acid precipitation reaction after acidity, it then will be described
The product heating of acid precipitation reaction carries out decarboxylic reaction, obtains generating the reaction mixture for having 4- methyl -5- ethyoxyl oxazole；
Step S40, it is separated and is purified to after being in neutrality with alkali neutralization by the reaction mixture, obtain 4- methyl -5- ethyoxyl
Oxazole.
2. the synthetic method of 4- methyl -5- ethyoxyl oxazole as described in claim 1, which is characterized in that in step slo:
The N- ethoxy oxalyl alanine ethyl ester, phosphorus oxychloride, the molar ratio of triethylamine and toluene are 1:(0.5~2): (2~
6): (5~10)；And/or
The reaction temperature of the cyclization reaction is 70~110 DEG C, and the reaction time is 2~10h.
3. the synthetic method of 4- methyl -5- ethyoxyl oxazole as claimed in claim 2, which is characterized in that in step slo:
The N- ethoxy oxalyl alanine ethyl ester, phosphorus oxychloride, the molar ratio of triethylamine and toluene are 1:1:3:7；And/or
The reaction temperature of the cyclization reaction is 85 DEG C, reaction time 7h.
4. the synthetic method of the 4- methyl -5- ethyoxyl oxazole as described in claims 1 to 3 any one, which is characterized in that step
Rapid S10 is specifically included:
After sequentially adding toluene, N- ethoxy oxalyl alanine ethyl ester and triethylamine into reaction kettle, under stirring to described
Phosphorus oxychloride is at the uniform velocity added dropwise in reaction kettle, then heating carries out cyclization reaction, and obtaining generating has 4- methyl -5- ethyoxyl oxazole ester
Cyclization reaction product；
Wherein, the dropping temperature of the phosphorus oxychloride is 40~70 DEG C, and time for adding is 0.5~2h.
5. the synthetic method of the 4- methyl -5- ethyoxyl oxazole as described in claim 4 any one, which is characterized in that in step
In rapid S10:
The dropping temperature of the phosphorus oxychloride is 55 DEG C, time for adding 1h.
6. the synthetic method of 4- methyl -5- ethyoxyl oxazole as described in claim 1, which is characterized in that in step S20:
The reaction temperature of the saponification is 50~80 DEG C, and the reaction time is 1~5h；And/or
The pH value of the saponification system is 12~14.
7. the synthetic method of 4- methyl -5- ethyoxyl oxazole as claimed in claim 6, which is characterized in that in step S20:
The reaction temperature of the saponification is 70 DEG C, reaction time 3h.
8. the synthetic method of 4- methyl -5- ethyoxyl oxazole as described in claim 1, which is characterized in that in step s 30:
The pH value of the acid precipitation reaction system is 1~3；And/or
The reaction temperature of the decarboxylic reaction is 50~90 DEG C, and the reaction time is 1~3h.
9. the synthetic method of 4- methyl -5- ethyoxyl oxazole as claimed in claim 8, which is characterized in that in step s 30:
The pH value of the acid precipitation reaction system is 1.5；And/or
The reaction temperature of the decarboxylic reaction is 60 DEG C, reaction time 2h.
10. the synthetic method of 4- methyl -5- ethyoxyl oxazole as described in claim 1, which is characterized in that step S40 is specific
Include:
The reaction mixture is distilled to after being in neutrality with alkali neutralization and collects distillate；
Organic phase is collected after being extracted with chloroform to the distillate；
The organic phase is distilled to remove chloroform therein, obtains 4- methyl -5- ethyoxyl oxazole.
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| CN111689920A (en) * | 2019-03-13 | 2020-09-22 | 江西天新药业股份有限公司 | Vitamin B6Recovery method of intermediate production tail gas |
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| CN110483433A (en) * | 2019-08-30 | 2019-11-22 | 厦门金达威维生素有限公司 | The synthetic method of 4- methyl -5- ethyoxyl oxazole acetoacetic ester |
| CN112174907A (en) * | 2020-10-12 | 2021-01-05 | 新发药业有限公司 | Environment-friendly preparation method of substituted oxazole compound |
| CN114163341A (en) * | 2021-12-13 | 2022-03-11 | 华中药业股份有限公司 | Preparation method of impurity TS-2A |
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Application publication date: 20190205 |