CN102086194A - Synthesis method of furazolidone - Google Patents
Synthesis method of furazolidone Download PDFInfo
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- CN102086194A CN102086194A CN 201110032710 CN201110032710A CN102086194A CN 102086194 A CN102086194 A CN 102086194A CN 201110032710 CN201110032710 CN 201110032710 CN 201110032710 A CN201110032710 A CN 201110032710A CN 102086194 A CN102086194 A CN 102086194A
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Abstract
The invention belongs to the field of organic chemical synthesis, and particularly relates to a synthesis method of furazolidone. The synthesis method comprises the following steps: introducing gasified ethylene oxide into a hydrazine hydrate through a coiler placed in hot water so as to prepare beta-hydroxyethylhydrazine; after cooling the beta-hydroxyethylhydrazine, adding sodium methoxide methyl alcohol solution and then stirring, and adding dimethyl carbonate so as to prepare 3-amino-2-oxazolidinone; and adding water in 3-amino-2-oxazolidinone, adding hydrochloric acid, rising the temperature, adding 5-nitryl furfural ester diacetate, and carrying out periodical warming so as to obtain the finished furazolidone. By using the synthesis method, the problems that the process is not environment-friendly, the requirement on equipment is high, the yield of the product is low, and the like in the prior art are effectively solved, and the yield of the product in the invention can be improved by 5-10%.
Description
Technical field
The invention belongs to the synthetic field of organic chemistry, be specifically related to a kind of processing condition and be simple and easy to be used for produce greatly and energy-conserving and environment-protective, and the synthetic method of the low Nifurazolidone of production cost.
Background technology
Nifurazolidone, chemical name: " 3-(5-nitrofuran methene amino)-the 2-oxazolidone ", having wider antimicrobial spectrum, sensitive organism is intestinal bacteria, anthrax bacillus, paratyphosum Bacterium, dysentery bacterium etc.Present stage, the synthesis technique about Nifurazolidone mainly contained:
Operational path one (industrial production usefulness): add thermal condensation by thanomin and urea, through nitrosification, cyclization, nitrosification again, reduction, the 3-amido-2-oxazolidinone; Obtain Nifurazolidone with the condensation of 5-nitryl furfural again.This not environmental protection of technology, waste gas, waste water are many, and energy consumption is big.
Operational path two: in the hydrazine hydrate by 65-75 ℃ of oxyethane (10.73 ℃ of boiling points) gasification feeding, boil off hydrazine hydrate, get the beta-hydroxyethyl hydrazine by distillation tower; Beta-hydroxyethyl hydrazine and methylcarbonate are made catalyzer at sodium methylate, and 65-75 ℃ of reaction gets 3-An oxazolidinone, adds 5-nitryl furfural (acid hydrolysis) again, makes solvent with methyl alcohol or ethanol, obtains Nifurazolidone.This process using distillation tower, the equipment complexity; The final step condensation is made solvent with methyl alcohol, ethanol; Yield is lower; Therefore be not used for industrial production always.
In addition, publication number be CN101450944A Chinese disclosure of the Invention the synthetic and process for purification of a kind of Nifurazolidone, the technical scheme of this patent documentation report is: add the formaldehyde that is equivalent to 5-nitryl furfural diethyl ester 30%～50% in 3-amino-2-oxazolidone and the 5-nitryl furfural diethyl ester reaction process, reaction gained Nifurazolidone crude product is refining with the EDTA aqueous solution, obtains the Nifurazolidone elaboration after the separation.The effect of used formaldehyde is the product decolouring in this invention technical scheme, and used EDTA effect is to remove metal ion neutralization product, and aforesaid operational path also needs to use.And the present invention does not need with formaldehyde and EDTA, and quality product is up to standard.
Summary of the invention
At the problem that above-mentioned prior art exists, the present invention does bigger innovation on the basis of second technology, aims to provide the synthetic method that a kind of technology environmental protection, energy consumption are little, be easy to the higher Nifurazolidone of industrialized production and yield.
For realizing purpose of the present invention, the contriver provides following technical scheme:
A kind of synthetic method of Nifurazolidone comprises that the following step poly-:
(1) preparation beta-hydroxyethyl hydrazine:
React in the hydrazine hydrate that the oxyethane feeding of gasification is 65-70 ℃, the oxyethane of described gasification feeds in the hydrazine hydrate by the coil pipe that is placed in the hot water, ventilation finishes back insulation 30-60 minute, first then air distillation boils off part (about 1/4th) hydrazine hydrate, and the hydrazine hydrate of surplus is done underpressure distillation, reaches 130-140 ℃ to temperature, the hydrazine hydrate evaporate to dryness, obtain the beta-hydroxyethyl hydrazine, the hydrazine hydrate that underpressure distillation steams (hydrazine hydrate content is generally more than 70%) is applied mechanically
(2) preparation 3-amido-2-oxazolidinone:
After treating beta-hydroxyethyl hydrazine cooling that step (1) obtains, at first adding methanol solution of sodium methylate stirs, add methylcarbonate again, be warming up to 68-73 ℃, insulation is more than 1 hour, and methyl alcohol and methylcarbonate are reclaimed in air distillation then, follows underpressure distillation again more than 20 minutes, obtain the 3-amido-2-oxazolidinone
(3) preparation Nifurazolidone:
Add entry in the 3-amido-2-oxazolidinone that step (2) obtains, add hydrochloric acid again, be warming up to 60-75 ℃, add the 5-nitryl furfural ester diacetate, be warming up to 75-80 ℃, insulation is more than 40 minutes, and then be warming up to 84-86 ℃, insulation was cooled to the blowing of back below 60 ℃ more than 30 minutes, obtained the Nifurazolidone finished product.
As preferably, according to the synthetic method of Nifurazolidone of the present invention, wherein, the hot water in the described step (1) is meant that temperature is 50-70 ℃ a water.Can guarantee that the oxyethane that gasifies fully heats, experiment shows that fully the ethylene oxide gas after the heating can improve yield 5-10% after feeding in the hydrazine hydrate.
As preferably, according to the synthetic method of Nifurazolidone of the present invention, wherein, hydrazine hydrate in the described step (1): oxyethane 1:0.1～0.2 in molar ratio feeds intake.Feeding intake by this proportioning both to guarantee that sufficient reacting carries out, and production cost is rationalized.Optimum mole ratio is hydrazine hydrate: oxyethane=1:0.1235, feeds intake by this proportioning, can also make the yield optimum of product.
As preferably,, wherein, treat to add again after the beta-hydroxyethyl hydrazine is cooled to below 50 ℃ methanol solution of sodium methylate in the described step (2) and stirred 10-20 minute according to the synthetic method of Nifurazolidone of the present invention.Be beneficial to the carrying out that reacts below, the carrying out of may command reaction.
As preferably, according to the synthetic method of Nifurazolidone of the present invention, wherein, beta-hydroxyethyl hydrazine in the described step (2): methylcarbonate: the mol ratio=1:1.03 of sodium methylate～1.04:0.08～0.09.Feeding intake by this proportioning both to guarantee that sufficient reacting carries out, and production cost is rationalized.Optimum mole ratio is the beta-hydroxyethyl hydrazine: methylcarbonate: the mol ratio=1:1.039:0.086 of sodium methylate, feed intake by this proportioning, and can also make the yield optimum of product.
As preferably, according to the synthetic method of Nifurazolidone of the present invention, wherein, the mass concentration of the methanol solution of sodium methylate in the described step (2) is 30%.The yield of product is than higher, in addition, crosses the lower concentration methanol solution of sodium methylate and can cause long or reaction of reaction times not exclusively, and the excessive concentrations methanol solution of sodium methylate can cause in the product impurity too high.
As preferably, according to the synthetic method of Nifurazolidone of the present invention, wherein, 3-amido-2-oxazolidinone in the described step (3): the mol ratio=1:1.01 of 5-nitryl furfural ester diacetate～1.03.Feeding intake by this proportioning both to guarantee that sufficient reacting carries out, and production cost is rationalized.Optimum mole ratio is the 3-amido-2-oxazolidinone: 5-nitryl furfural ester diacetate=1:1.02, feed intake by this proportioning, and can also make the yield optimum of product.
As preferably, according to the synthetic method of Nifurazolidone of the present invention, wherein, the hydrazine hydrate (hydrazine hydrate content is 50～60%) that air distillation steams in the described step (1) is removed moisture and is applied mechanically after hydrazine hydrate content is more than 70%.So operation can further reduce production costs.
As preferably, according to the synthetic method of Nifurazolidone of the present invention, wherein, long 3 meters to 100 meters of the coil pipe in the described step (1).The oxyethane that the too short words of coil pipe can cause gasifying can not fully heat; Long meeting increases energy consumption.
As preferably, according to the synthetic method of Nifurazolidone of the present invention, wherein, the feeding speed of the oxyethane of the gasification in the described step (1) is 0.3～0.4mol/ hour.The feeding speed of the oxyethane of control gasification rationally helps reaction carries out, and cost also relatively rationally.
Term among the present invention all is this area technique means commonly used as normal pressure distillation, underpressure distillation etc., no longer makes special instruction at this.
Specifically, technical scheme of the present invention is:
(1) elder generation adds the hydrazine hydrate of 80% hydrazine hydrate or recovery, is warmed up to 65-70 ℃.Begin the oxyethane that gasifies, ethylene oxide gas is by the coil pipe of 3-100 rice, coil pipe is put into 50-70 ℃ water, the oxyethane of heat feeds in the hydrazine hydrate, control feeding speed (per hour feeding about 15g), the hydrazine hydrate temperature is controlled at about 70 ℃, after ventilation finishes, 70 ℃ of insulations 30-60 minute.Without distillation tower, the hydrazine hydrate of first air distillation about 1/4th (its content 50% to 60%, boil off partly water-content reach more than 70% apply mechanically again); Hydrazine hydrate is collected in remaining underpressure distillation again, reaches 130-140 ℃ to temperature, the hydrazine hydrate evaporate to dryness of trying one's best, beta-hydroxyethyl hydrazine (this hydrazine hydrate content is applied mechanically more than 70% always).Reaction formula is as follows:
(2) the beta-hydroxyethyl hydrazine is cooled to about 50 ℃, add methanol solution of sodium methylate earlier, stirred 10-20 minute, add methylcarbonate again, temperature is raised to about 70 ℃, and insulation is more than 1 hour, and methyl alcohol and methylcarbonate are reclaimed in air distillation then, then underpressure distillation got the 3-amido-2-oxazolidinone more than 20 minutes again.Reaction formula is as follows:
(3) in the 3-amido-2-oxazolidinone, add entry, slowly add hydrochloric acid, be warmed up to then about 65 ℃, add the 5-nitryl furfural ester diacetate, be warming up to 75-80 ℃, be incubated after at least 40 minutes, be warming up to 84-86 ℃, be incubated after at least 30 minutes, be cooled to blowing below 60 ℃, get the Nifurazolidone finished product.Reaction formula is as follows:
Compared with prior art, the present invention has the following advantages:
The present invention has the technology environmental protection, equipment is simple, easy-to-use commercial scale production, the characteristics that product yield is high.
1. oxyethane gasification, ethylene oxide gas be by coil pipe (this coil pipe is put into 50-70 ℃ water), and long 3 meters to 100 meters of coil pipe, gas be through fully heating, and feeds in 65-70 ℃ the hydrazine hydrate again, can improve yield 5-10%.2. remove distillation tower, use distillation instead, though there is micro-beta-hydroxyethyl hydrazine to take out of like this, hydrazine hydrate repeats to apply mechanically, and yield is not had influence, saves large number quipments, and reduces distillation time.3. water as solvent is adopted in the final step reaction, has reduced cost, has also reduced danger.4. experiment shows that the addition sequence of catalyzer sodium methylate of the present invention and amount thereof also have raising to product yield.(the present invention has been used for industrial production).
Embodiment
Below in conjunction with embodiment, be described more specifically content of the present invention.Should be appreciated that enforcement of the present invention is not limited to the following examples, all will fall into protection domain of the present invention any pro forma accommodation and/or the change that the present invention made.
In the present invention, if not refer in particular to, all equipment and raw material etc. all can be buied from market or the industry is commonly used.Method among the following embodiment if no special instructions, is the ordinary method of this area.
Embodiment 1:
Add 80% hydrazine hydrate 250g earlier, be warmed up to 70 ℃, begin the oxyethane that gasifies, ethylene oxide gas is by 5 meters coil pipes, and coil pipe is put into 70 ℃ water, and the ethylene oxide gas of heat feeds in the hydrazine hydrate, control ventilation speed, the hydrazine hydrate temperature is at 70 ℃, and about 1.5 hours of the 23.7g time of ventilation, 70 ℃ are incubated 1 hour.Then, 60g hydrazine hydrate (content boils off part moisture hydrazine hydrate content is applied mechanically more than 50%) is removed in first air distillation after more than 70%, (content is more than 70 ℃ for underpressure distillation collection hydrazine hydrate again, this hydrazine hydrate is applied mechanically always), reach 135 ℃ to temperature, the hydrazine hydrate evaporate to dryness of trying one's best.Get beta-hydroxyethyl hydrazine 40g.
Beta-hydroxyethyl hydrazine 40g is chilled to 50 ℃, add 30% methanol solution of sodium methylate 8.2g earlier, stirred 10 minutes, add methylcarbonate 49.2g again, temperature rises to 70 ℃, is incubated 1 hour, and methyl alcohol and methylcarbonate are reclaimed in first then air distillation, follow underpressure distillation again 20 minutes, get the 3-amido-2-oxazolidinone.
In the 3-amido-2-oxazolidinone, add 300g water, add the 60ml technical hydrochloric acid, be warming up to 65 ℃, add 5-nitryl furfural ester diacetate 98g, be warming up to 75 ℃, be incubated after 40 minutes, be warming up to 84 ℃, be incubated 30 minutes, be cooled to 60 ℃ after blowing, Nifurazolidone dry product 87.0g.
The fusing point that records the Nifurazolidone dry product is 257-259 ℃ (document is 255-259 ℃), and the HPLC purity assay is 99.5%, residue on ignition: less than 0.08%, total recovery is that 71.72%(is in oxyethane).
Embodiment 2
Add 80% hydrazine hydrate 250g earlier, be warmed up to 65 ℃, begin the oxyethane that gasifies, ethylene oxide gas is by 3 meters coil pipes, and coil pipe is put into 50 ℃ water, and the oxyethane of heat feeds in the hydrazine hydrate, control ventilation speed, the hydrazine hydrate temperature is at 65 ℃, and about 1.5 hours of the 23.7g time of ventilation, 65 ℃ are incubated 1 hour.Then, 60g hydrazine hydrate (content boils off part moisture hydrazine hydrate content is applied mechanically more than 50%) is removed in first air distillation after more than 70%, (content is more than 70 ℃ for underpressure distillation collection hydrazine hydrate again, this hydrazine hydrate is applied mechanically always), reach 140 ℃ to temperature, the hydrazine hydrate evaporate to dryness of trying one's best.Get beta-hydroxyethyl hydrazine 40g.
Beta-hydroxyethyl hydrazine 40g is chilled to 50 ℃, add 30% methanol solution of sodium methylate 8.2g earlier, stirred 20 minutes, add methylcarbonate 49.2g again, temperature rises to 68 ℃, is incubated 1 hour, then, methyl alcohol and methylcarbonate are reclaimed in elder generation's air distillation, follow underpressure distillation again 20 minutes, get the 3-amido-2-oxazolidinone.
In the 3-amido-2-oxazolidinone, add 300g water, add the 60ml technical hydrochloric acid, be warming up to 60 ℃, add 5-nitryl furfural ester diacetate 98g, be warming up to 80 ℃, be incubated after 40 minutes, be warming up to 86 ℃, be incubated 30 minutes, be cooled to 60 ℃ after blowing, Nifurazolidone dry product 85.7g.
The fusing point that records the Nifurazolidone dry product is 257-259 ℃ (document is 255-259 ℃), and the HPLC purity assay is 99.8%, residue on ignition: less than 0.08%, total recovery is that 70.65%(is in oxyethane).
Embodiment 3
Add 70% earlier and reclaim hydrazine hydrate 285.7g, begin the oxyethane that gasifies, ethylene oxide gas is by 100 meters coil pipes, coil pipe is put into 70 ℃ water, the oxyethane of heat feeds in the hydrazine hydrate, control ventilation speed, and the hydrazine hydrate temperature is at 70 ℃, about 1.5 hours of the 23.7g time of ventilation, 70 ℃ are incubated 1 hour.Then, 60g hydrazine hydrate (content boils off part moisture hydrazine hydrate content is applied mechanically more than 50%) is removed in first air distillation after more than 70%, (content is more than 70 ℃ for underpressure distillation collection hydrazine hydrate again, this hydrazine hydrate is applied mechanically always), reach 130 ℃ to temperature, the hydrazine hydrate evaporate to dryness of trying one's best.Get beta-hydroxyethyl hydrazine 40g.
Beta-hydroxyethyl hydrazine 40g is chilled to 50 ℃, add 30% methanol solution of sodium methylate 8.2g earlier, stirred 12 minutes, add methylcarbonate 49.2g again, temperature rises to 73 ℃, is incubated 1 hour, then, methyl alcohol and methylcarbonate are reclaimed in elder generation's air distillation, follow underpressure distillation again 20 minutes, get the 3-amido-2-oxazolidinone.
In the 3-amido-2-oxazolidinone, add 300g water, add the 60ml technical hydrochloric acid, be warming up to 75 ℃, add 5-nitryl furfural ester diacetate 98g, be warming up to 80 ℃, be incubated after 40 minutes, be warming up to 85 ℃, be incubated 30 minutes, be cooled to 60 ℃ after blowing, Nifurazolidone dry product 87.5g.
The fusing point that records the Nifurazolidone dry product is 257-259 ℃ (document is 255-259 ℃), and the HPLC purity assay is 99.5%, residue on ignition: less than 0.08%, total recovery is that 72.13%(is in oxyethane).
Embodiment 4
Add 80% hydrazine hydrate 250g earlier, be warmed up to 70 ℃, begin the oxyethane that gasifies, ethylene oxide gas is by 5 meters coil pipes, and coil pipe is put into 70 ℃ water, and the oxyethane of heat feeds in the hydrazine hydrate, control ventilation speed, the hydrazine hydrate temperature is at 70 ℃, and about 1.5 hours of the 23.7g time of ventilation, 70 ℃ are incubated 0.5 hour.With the underpressure distillation of glass distillation column, reclaim hydrazine hydrate, reach 135 ℃ to temperature, the hydrazine hydrate evaporate to dryness of trying one's best.Get beta-hydroxyethyl hydrazine 40.2g.
Beta-hydroxyethyl hydrazine 40.2g is chilled to 50 ℃, add 30% methanol solution of sodium methylate 8.2g earlier, stirred 18 minutes, add methylcarbonate 49.2g again, temperature rises to 70 ℃, is incubated 1 hour, then, methyl alcohol and methylcarbonate are reclaimed in elder generation's air distillation, follow underpressure distillation again 20 minutes, get the 3-amido-2-oxazolidinone.
In the 3-amido-2-oxazolidinone, add 300g water, add the 60ml technical hydrochloric acid, be warming up to 65 ℃, add 5-nitryl furfural ester diacetate 98g, be warming up to 76 ℃, be incubated after 40 minutes, be warming up to 84 ℃, be incubated 30 minutes, be cooled to 60 ℃ after blowing, Nifurazolidone dry product 86.5g.
The fusing point that records the Nifurazolidone dry product is 257-259 ℃ (document is 255-259 ℃), and the HPLC purity assay is 99.5%, residue on ignition: less than 0.08%, total recovery is that 71.31%(is in oxyethane).
Comparative example 1
Add 80% hydrazine hydrate 250g earlier, be warmed up to 70 ℃, begin the oxyethane that gasifies, ethylene oxide gas is by 5 meters coil pipes, and coil pipe is put into 70 ℃ water, and the oxyethane of heat feeds in the hydrazine hydrate, control ventilation speed, the hydrazine hydrate temperature is at 70 ℃, and about 1.5 hours of the 23.7g time of ventilation, 70 ℃ are incubated 1 hour.Then, 60g hydrazine hydrate (content boils off part moisture hydrazine hydrate content is applied mechanically more than 50%) is removed in first air distillation after more than 70%, (content is more than 70 ℃ for underpressure distillation collection hydrazine hydrate again, this hydrazine hydrate is applied mechanically always), reach 135 ℃ to temperature, the hydrazine hydrate evaporate to dryness of trying one's best.Get beta-hydroxyethyl hydrazine 40g.
Beta-hydroxyethyl hydrazine 40g is chilled to 50 ℃, adds methylcarbonate 49.2g earlier, stirred 20 minutes, add 30% methanol solution of sodium methylate 5.6g again.Temperature rises to 70 ℃, is incubated 1 hour, and then, methyl alcohol and methylcarbonate are reclaimed in first air distillation, follow underpressure distillation again 20 minutes, get the 3-amido-2-oxazolidinone.
In the 3-amido-2-oxazolidinone, add 300g water, add the 60ml technical hydrochloric acid, be warming up to about 65 ℃, add 5-nitryl furfural ester diacetate 98g, be warming up to 75 ℃, be incubated after 40 minutes, be warming up to 84 ℃, be incubated 30 minutes, be cooled to 60 ℃ after blowing, Nifurazolidone dry product 83.9g.
The fusing point that records the Nifurazolidone dry product is 257-259 ℃ (document is 255-259 ℃), and the HPLC purity assay is 99.5%, residue on ignition: less than 0.08%, total recovery is that 69.17%(is in oxyethane).
Comparative example 2
Add 80% hydrazine hydrate 250g earlier, be warmed up to 70 ℃, begin the oxyethane that gasifies, the oxyethane of gasification directly feeds in the hydrazine hydrate, and control ventilation speed, hydrazine hydrate temperature are at 70 ℃, and about 1.5 hours of the 23.7g time of ventilation, 70 ℃ are incubated 1 hour.Then, 60g hydrazine hydrate (content boils off part moisture hydrazine hydrate content is applied mechanically more than 50%) is removed in first air distillation after more than 70%, (content is more than 70 ℃ for underpressure distillation collection hydrazine hydrate again, this hydrazine hydrate is applied mechanically always), reach 135 ℃ to temperature, the hydrazine hydrate evaporate to dryness of trying one's best.Get beta-hydroxyethyl hydrazine 40g.
Beta-hydroxyethyl hydrazine 40g is chilled to 50 ℃, adds methylcarbonate 49.2g earlier, stirred 10 minutes, add 30% methanol solution of sodium methylate 5.6g again.Temperature rises to 70 ℃, is incubated 1 hour, and then, methyl alcohol and methylcarbonate are reclaimed in first air distillation, follow underpressure distillation again 20 minutes, get the 3-amido-2-oxazolidinone.
In the 3-amido-2-oxazolidinone, add 300g water, add the 60ml technical hydrochloric acid, be warming up to 65 ℃, add 5-nitryl furfural ester diacetate 98g, be warming up to 80 ℃, be incubated after 40 minutes, be warming up to 86 ℃, be incubated 30 minutes, be cooled to 60 ℃ after blowing, Nifurazolidone dry product 79.2g.
The fusing point that records the Nifurazolidone dry product is 257-259 ℃ (document is 255-259 ℃), and the HPLC purity assay is 99.3%, residue on ignition: less than 0.08%, total recovery is that 65.29%(is in oxyethane).
Comparative example 3
Add 80% hydrazine hydrate 250g earlier, be warmed up to 70 ℃, begin the oxyethane that gasifies, the oxyethane of gasification directly feeds in the hydrazine hydrate, and control ventilation speed, hydrazine hydrate temperature are at 70 ℃, and about 1.5 hours of the 23.7g time of ventilation, 70 ℃ are incubated 1 hour.Then, 60g hydrazine hydrate (content boils off part moisture hydrazine hydrate content is applied mechanically more than 50%) is removed in first air distillation after more than 70%, (content is more than 70 ℃ for underpressure distillation collection hydrazine hydrate again, this hydrazine hydrate is applied mechanically always), reach 135 ℃ to temperature, the hydrazine hydrate evaporate to dryness of trying one's best.Get beta-hydroxyethyl hydrazine 40g.
Beta-hydroxyethyl hydrazine 40g is chilled to 50 ℃, adds methylcarbonate 49.2g earlier, stirred 20 minutes, add 30% methanol solution of sodium methylate 3.8g again.Temperature rises to 70 ℃, is incubated 1 hour, and then, methyl alcohol and methylcarbonate are reclaimed in first air distillation, follow underpressure distillation again 20 minutes, get the 3-amido-2-oxazolidinone.
In the 3-amido-2-oxazolidinone, add 300g water, add the 60ml technical hydrochloric acid, be warming up to 65 ℃, add 5-nitryl furfural ester diacetate 98g, be warming up to 78 ℃, be incubated after 40 minutes, be warming up to 85 ℃, be incubated 30 minutes, be cooled to 60 ℃ after blowing, Nifurazolidone dry product 74.9g.
The fusing point that records the Nifurazolidone dry product is 257-259 ℃ (document is 255-259 ℃), and the HPLC purity assay is 99.2%, residue on ignition: less than 0.08%, total recovery is that 61.75%(is in oxyethane).
Above preferred embodiment just is used for description and interpretation content of the present invention, does not constitute the restriction to content of the present invention.Discover that in the synthetic method of Nifurazolidone of the present invention, hydrazine hydrate in the step (1): the mol ratio of oxyethane is controlled between 1:0.1～0.2; Beta-hydroxyethyl hydrazine in the step (2): methylcarbonate: the mol ratio of sodium methylate is controlled between 1:1.03～1.04:0.08～0.09; 3-amido-2-oxazolidinone in the step (3): the mol ratio of 5-nitryl furfural ester diacetate is controlled between 1:1.01～1.03, those of ordinary skill in the art makes modifications and variations according to above preferred embodiment, do not need to pay creative work and can realize goal of the invention of the present invention, therefore, give unnecessary details no longer one by one herein.
Although the contriver has done in more detail the present invention and has enumerated, but, the content that those skilled in the art is disclosed according to summary of the invention part and embodiment, can make various modifications or/and to replenish or adopt similar mode to substitute be obvious to described specific embodiment, and can realize technique effect of the present invention.The term that occurs among the present invention is used for the elaboration of technical solution of the present invention and understanding are not construed as limiting the invention.
Claims (10)
1. the synthetic method of a Nifurazolidone is characterized in that, described synthetic method comprises that the following step poly-:
(1) preparation beta-hydroxyethyl hydrazine:
React in the hydrazine hydrate that the oxyethane feeding of gasification is 65-70 ℃, the oxyethane of described gasification feeds in the hydrazine hydrate by the coil pipe that is placed in the hot water, ventilation finishes back insulation 30-60 minute, first then air distillation boils off partially hydrated hydrazine, and the hydrazine hydrate of surplus is done underpressure distillation, reaches 130-140 ℃ to temperature, the hydrazine hydrate evaporate to dryness, obtain the beta-hydroxyethyl hydrazine, the hydrazine hydrate that underpressure distillation steams is applied mechanically
(2) preparation 3-amido-2-oxazolidinone:
After treating beta-hydroxyethyl hydrazine cooling that step (1) obtains, at first adding methanol solution of sodium methylate stirs, add methylcarbonate again, be warming up to 68-73 ℃, insulation is more than 1 hour, and methyl alcohol and methylcarbonate are reclaimed in air distillation then, follows underpressure distillation again more than 20 minutes, obtain the 3-amido-2-oxazolidinone
(3) preparation Nifurazolidone:
Add entry in the 3-amido-2-oxazolidinone that step (2) obtains, add hydrochloric acid again, be warming up to 60-75 ℃, add the 5-nitryl furfural ester diacetate, be warming up to 75-80 ℃, insulation is more than 40 minutes, and then be warming up to 84-86 ℃, insulation was cooled to the blowing of back below 60 ℃ more than 30 minutes, obtained the Nifurazolidone finished product.
2. the synthetic method of Nifurazolidone according to claim 1 is characterized in that, the hot water in the described step (1) is meant that temperature is 50-70 ℃ a water.
3. the synthetic method of Nifurazolidone according to claim 1 is characterized in that, hydrazine hydrate in the described step (1): oxyethane 1:0.1～0.2 in molar ratio feeds intake.
4. the synthetic method of Nifurazolidone according to claim 1 is characterized in that, treats to add after the beta-hydroxyethyl hydrazine is cooled to below 50 ℃ methanol solution of sodium methylate in the described step (2) again and stirs 10-20 minute.
5. the synthetic method of Nifurazolidone according to claim 1 is characterized in that, beta-hydroxyethyl hydrazine in the described step (2): methylcarbonate: the mol ratio=1:1.03 of sodium methylate～1.04:0.08～0.09.
6. the synthetic method of Nifurazolidone according to claim 1 is characterized in that, the mass concentration of the methanol solution of sodium methylate in the described step (2) is 30%.
7. the synthetic method of Nifurazolidone according to claim 1 is characterized in that, 3-amido-2-oxazolidinone in the described step (3): the mol ratio=1:1.01 of 5-nitryl furfural ester diacetate～1.03.
8. the synthetic method of Nifurazolidone according to claim 1 is characterized in that, the hydrazine hydrate that air distillation steams in the described step (1) is removed moisture and applied mechanically after hydrazine hydrate content is more than 70%.
9. the synthetic method of Nifurazolidone according to claim 1 is characterized in that, long 3 meters to 100 meters of the coil pipe in the described step (1).
10. the synthetic method of Nifurazolidone according to claim 1 is characterized in that, the feeding speed of the oxyethane of the gasification in the described step (1) is 0.3～0.4mol/ hour.
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| CN104876833A (en) * | 2015-06-16 | 2015-09-02 | 杨东 | Microreactor device for producing 2-hydroxyethylhydrazine and preparation process |
| CN107118123A (en) * | 2017-06-07 | 2017-09-01 | 李博强 | A kind of method for preparing 2 hydroxyethylhydrazines |
| CN111039886A (en) * | 2018-10-12 | 2020-04-21 | 上海安谱实验科技股份有限公司 | Stable isotope labeled furazolidone metabolite and synthetic method thereof |
| CN111303063A (en) * | 2018-12-12 | 2020-06-19 | 中国农业科学院农业质量标准与检测技术研究所 | Synthetic method of furazolidone metabolite AOZ |
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| CN103420934A (en) * | 2013-06-07 | 2013-12-04 | 华中农业大学 | Synthesis method of 5- methylmorpholine-3-amino-2-oxazolidinyl ketone |
| CN104876833A (en) * | 2015-06-16 | 2015-09-02 | 杨东 | Microreactor device for producing 2-hydroxyethylhydrazine and preparation process |
| CN104876833B (en) * | 2015-06-16 | 2016-08-31 | 杨东 | A kind of microreactor device producing 2-hydroxyethylhydrazine and preparation technology |
| CN107118123A (en) * | 2017-06-07 | 2017-09-01 | 李博强 | A kind of method for preparing 2 hydroxyethylhydrazines |
| CN109694359B (en) * | 2017-10-24 | 2020-11-10 | 中国农业科学院农业质量标准与检测技术研究所 | Synthetic method of nitrofuran metabolite-furazolidone AOZ-D4 |
| CN111039886A (en) * | 2018-10-12 | 2020-04-21 | 上海安谱实验科技股份有限公司 | Stable isotope labeled furazolidone metabolite and synthetic method thereof |
| CN111303063A (en) * | 2018-12-12 | 2020-06-19 | 中国农业科学院农业质量标准与检测技术研究所 | Synthetic method of furazolidone metabolite AOZ |
| CN111303064A (en) * | 2018-12-12 | 2020-06-19 | 中国农业科学院农业质量标准与检测技术研究所 | Synthetic method of furazolidone metabolite AOZ |
| CN111303064B (en) * | 2018-12-12 | 2022-08-23 | 中国农业科学院农业质量标准与检测技术研究所 | Synthetic method of furazolidone metabolite AOZ |
| CN114195674A (en) * | 2020-09-02 | 2022-03-18 | 中国科学院大连化学物理研究所 | Micro-reaction system and method for synthesizing hydroxyethyl hydrazine |
| CN114195674B (en) * | 2020-09-02 | 2022-12-27 | 中国科学院大连化学物理研究所 | Micro-reaction system and method for synthesizing hydroxyethyl hydrazine |
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