CN109776424B - Novel method for preparing L-phenylglycine precursor phenylhydantoin by using MIC reactor - Google Patents
Novel method for preparing L-phenylglycine precursor phenylhydantoin by using MIC reactor Download PDFInfo
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- CN109776424B CN109776424B CN201910059874.7A CN201910059874A CN109776424B CN 109776424 B CN109776424 B CN 109776424B CN 201910059874 A CN201910059874 A CN 201910059874A CN 109776424 B CN109776424 B CN 109776424B
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Abstract
The invention relates to a novel method for preparing a levo-phenylglycine precursor phenylhydantoin by using an MIC reactor. The existing process adopts a reaction kettle for intermittent production, the amount of unorganized waste gas is large, the possibility of leakage of sealing surface materials exists in the material transferring process, and the potential safety hazard and the environmental protection risk are high. According to the invention, ammonium bicarbonate (pure), sodium cyanide (30% aqueous solution) and benzaldehyde are pumped into an MIC reactor preheated to 60 ℃ in a mass ratio of 8.2 to 10 for mixing reaction, the prepared solution is hydrolyzed to obtain the DL-phenylglycine, a discharge port of the MIC reactor is connected with a gas-liquid separation tank, a gas outlet of the gas-liquid separation tank is connected with a pressure gauge to display the pressure of the system, and the gas-liquid separation tank is also connected with a back pressure valve to carry out back pressure on the whole system. The invention adopts the ammonium bicarbonate aqueous solution to replace solid ammonium bicarbonate, successfully avoids dust and unorganized waste gas generated during feeding of the solid ammonium bicarbonate, reduces the dosage of the ammonium bicarbonate from 1.5 equivalent to 1.1 equivalent, and has obvious economic benefit.
Description
Technical Field
The invention relates to a novel method for preparing a levo-phenylglycine precursor phenylhydantoin by using an MIC reactor.
Background
At present, manufacturers at home and abroad basically produce the levo-phenylglycine by a Bucherer-Bergs method, in the method, benzaldehyde is taken as a starting raw material, under the action of sodium cyanide (or potassium cyanide), the benzaldehyde and excessive ammonium bicarbonate (or ammonium carbonate) are mixed to prepare phenylhydantoin, and the phenylhydantoin is hydrolyzed and split to prepare the levo-phenylglycine, wherein the yield of the phenylhydantoin (calculated by benzaldehyde) is about 80%, and the wastewater treatment difficulty is high.
The Bucherer-Bergs method uses a large amount of virulent sodium cyanide (or potassium cyanide), a small amount of hydrogen cyanide gas is generated in the reaction, and CN-exists in the reaction liquid, so that the Bucherer-Bergs method has higher requirements on equipment safety operation, occupational health control measures and environmental protection treatment facilities. In addition, the process adopts a reaction kettle for intermittent production, the amount of unorganized waste gas is large, the possibility of leakage of sealing surface materials exists in the material transferring process, and the potential safety hazard and the environmental protection risk are high.
Disclosure of Invention
Aiming at the problems in the prior art, the invention provides a novel method for preparing the L-phenylglycine precursor phenylhydantoin by using an MIC reactor.
The technical scheme adopted by the invention is as follows: a new method for preparing a levo-phenylglycine precursor phenylhydantoin by an MIC reactor is characterized in that ammonium bicarbonate (pure), sodium cyanide (30% aqueous solution) and benzaldehyde are pumped into the MIC reactor preheated to 60 ℃ in a mass ratio of 8.2. Pumping into an MIC reactor preheated to 60 ℃ for mixing reaction, hydrolyzing the prepared liquid to obtain the DL-phenylglycine, connecting a discharge port of the MIC reactor with a gas-liquid separation tank, connecting a gas outlet of the gas-liquid separation tank with a pressure gauge for displaying the pressure of the system, and connecting a back pressure valve to the gas-liquid separation tank for carrying out back pressure on the whole system. The invention prepares the racemic phenylglycine by liquid alkali hydrolysis, and then prepares the levophenylglycine by resolution of the dextro camphorsulfonic acid, and the L-phenylglycine is a semi-synthetic important intermediate of ampicillin, cephalexin and other beta-lactam antibiotics. The MIC reactor related by the invention has low heat buffer demand and extremely high automation degree, meets the requirement of clean production, and represents the development direction of green chemistry and automation.
When in preparation, ammonium bicarbonate water solution accounting for 60 percent of the total mass of the raw materials is pumped firstly, and then the three raw materials are pumped at the same time by setting the flow rate.
When in preparation, ammonium bicarbonate aqueous solution, 30 percent sodium cyanide and benzaldehyde are respectively and continuously pumped into an MIC reactor at the flow rates of 2800L/h, 940L/h and 600L/h.
And a nanoscale 2205 stainless steel microchannel insert is inserted into the MIC reactor. Enhancing the shearing action of the benzaldehyde and 30 percent sodium cyanide during mixing and strengthening the mixing process
The internal channels of the MIC reactor are arranged in parallel, and the size of a single channel is unchanged. Slowing down the amplification effect of the Bucherer-Bergs reaction process.
The invention has the beneficial effects that: the environmental protection policy requirements of 'closed production process replacing open production process' and 'continuous and automatic production process replacing intermittent production process' can be realized, and meanwhile, the preparation method of the MIC reactor belongs to the category of 'micro reaction and continuous flow' and meets the current safety policy requirements.
The invention adopts the ammonium bicarbonate aqueous solution to replace solid ammonium bicarbonate, successfully avoids dust and unorganized waste gas generated during feeding of the solid ammonium bicarbonate, reduces the dosage of the ammonium bicarbonate from 1.5 equivalent to 1.1 equivalent, and has obvious economic benefit. The most important is that the yield of the phenylhydantoin (calculated by benzaldehyde) can be improved from the existing 80 percent to 92 percent by adopting the preparation method of the MIC reactor, the yield is improved by 12 percent, and the economic benefit is obvious.
Drawings
FIG. 1 is a schematic diagram of the synthetic route of the present invention.
FIG. 2 is a schematic diagram of the reaction mechanism of the present invention.
FIG. 3 shows a schematic diagram of the MIC reactor of the present invention.
Detailed Description
The invention is described in detail below with reference to the attached drawing figures:
as shown in figures 1-3, a discharge port of the MIC reactor is connected with a gas-liquid separation tank, a gas outlet of the gas-liquid separation tank is connected with a pressure gauge to display the pressure of the system, and the gas-liquid separation tank is also connected with a back pressure valve to carry out back pressure on the whole system. The inside of the MIC reactor is inserted with a nano 2205 stainless steel microchannel insert. The internal channels of the MIC reactor are arranged in parallel, and the size of a single channel is unchanged. The preparation method comprises the following steps:
example 1: 820kg of ammonium bicarbonate (pure), 1580kg of sodium cyanide (30% aqueous solution) and 1000kg of benzaldehyde are respectively pumped into an MIC reactor preheated to 60 ℃ from an inlet of the MIC reactor by a metering pump, about 500kg of ammonium bicarbonate aqueous solution is firstly pumped, then the benzaldehyde, the ammonium bicarbonate aqueous solution and 30% of sodium cyanide are simultaneously pumped, and the flow rate is set on the basis that three raw materials are pumped simultaneously. 1644kg of DL-phenylglycine is obtained by hydrolyzing the preparation solution, and the detection result is as follows: loss on drying: 19.23 percent; sulfate radical: 2ppm; alkali light absorption value: 0.277AU.
Example 2:
and continuously pumping ammonium bicarbonate water solution, 30% sodium cyanide and benzaldehyde into an MIC reactor preheated to 60 ℃ at the flow rates of 2800L/h, 940L/h and 600L/h respectively to continuously obtain preparation liquid meeting the requirements, and hydrolyzing the preparation liquid to obtain qualified racemic phenylglycine. In the continuous preparation process, attention needs to be paid to whether the reaction liquid turns blue or not, if the reaction liquid turns blue, the reaction liquid shows that sodium cyanide in the reaction system is excessive, and the feeding amount of 30 percent of sodium cyanide needs to be reduced in time.
The above description is only an example of the present invention, and the present invention is not limited to the above example, and many modifications are possible. All modifications which can be derived or suggested by a person skilled in the art from the disclosure of the present invention are to be considered within the scope of the invention.
Claims (4)
1. A method for preparing DL-phenylglycine by an MIC reactor is characterized in that pure ammonium bicarbonate, aqueous solution containing 30% of sodium cyanide and benzaldehyde are pumped into the MIC reactor preheated to 60 ℃ according to the mass ratio of 8.2 to 15.8 for mixed reaction, prepared liquid is hydrolyzed to obtain the DL-phenylglycine, a discharge port of the MIC reactor is connected with a gas-liquid separation tank, a gas outlet of the gas-liquid separation tank is connected with a pressure gauge to display system pressure, the gas-liquid separation tank is also connected with a back pressure valve to carry out back pressure on the whole system, ammonium bicarbonate aqueous solution accounting for 60% of the total mass of the ammonium bicarbonate aqueous solution is pumped firstly during preparation, and then the flow setting is carried out to pump the three raw materials at the same time.
2. A method for preparing DL-phenylglycine in a MIC reactor according to claim 1, wherein the method comprises continuously pumping ammonium bicarbonate solution, 30% NaCN, and benzaldehyde into the MIC reactor at 2800L/h, 940L/h, and 600L/h.
3. The method for preparing DL-phenylglycine according to claim 1, wherein the MIC reactor has a nano-scale 2205 stainless steel microchannel insert inserted therein.
4. The method for preparing DL-phenylglycine according to claim 3, in a MIC reactor, wherein the internal channels of the MIC reactor are arranged in parallel and the size of each channel is unchanged.
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| CN111269134B (en) * | 2020-04-01 | 2022-09-20 | 九江中星医药化工有限公司 | Preparation method of phenylglycine and derivatives thereof |
| CN112250634B (en) * | 2020-10-22 | 2022-08-12 | 苏州亚科科技股份有限公司 | Preparation method of 4-phenylimidazole |
| CN114516811A (en) * | 2022-03-07 | 2022-05-20 | 浙江云涛生物技术股份有限公司 | Method for racemization reaction of phenylglycine in alkaline environment |
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| CN103086905A (en) * | 2011-09-07 | 2013-05-08 | 浙江云涛生物技术股份有限公司 | Preparation method for DL-phenylglycine |
| CN104876876A (en) * | 2014-02-28 | 2015-09-02 | 李宽义 | Clean production method for continuously synthesizing hydantoin |
| CN106083628A (en) * | 2016-06-01 | 2016-11-09 | 河北诚信有限责任公司 | A kind of method preparing p-chlorophenylglycine |
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| CN103086905A (en) * | 2011-09-07 | 2013-05-08 | 浙江云涛生物技术股份有限公司 | Preparation method for DL-phenylglycine |
| CN104876876A (en) * | 2014-02-28 | 2015-09-02 | 李宽义 | Clean production method for continuously synthesizing hydantoin |
| CN106083628A (en) * | 2016-06-01 | 2016-11-09 | 河北诚信有限责任公司 | A kind of method preparing p-chlorophenylglycine |
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