CN106083628B - A kind of method for preparing p-chlorophenylglycine - Google Patents
A kind of method for preparing p-chlorophenylglycine Download PDFInfo
- Publication number
- CN106083628B CN106083628B CN201610383761.9A CN201610383761A CN106083628B CN 106083628 B CN106083628 B CN 106083628B CN 201610383761 A CN201610383761 A CN 201610383761A CN 106083628 B CN106083628 B CN 106083628B
- Authority
- CN
- China
- Prior art keywords
- solution
- reaction
- chlorophenylglycine
- pipeline
- chlorobenzene
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- FWALJUXKWWBNEO-UHFFFAOYSA-N 2-(4-chloroanilino)acetic acid Chemical compound OC(=O)CNC1=CC=C(Cl)C=C1 FWALJUXKWWBNEO-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 51
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 claims abstract description 28
- MFDCPGMRJMPEIQ-UHFFFAOYSA-N C(CO)(=O)NC(=O)N.ClC1=CC=CC=C1 Chemical compound C(CO)(=O)NC(=O)N.ClC1=CC=CC=C1 MFDCPGMRJMPEIQ-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000001099 ammonium carbonate Substances 0.000 claims abstract description 28
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 claims abstract description 26
- 235000012538 ammonium bicarbonate Nutrition 0.000 claims abstract description 26
- AVPYQKSLYISFPO-UHFFFAOYSA-N 4-chlorobenzaldehyde Chemical compound ClC1=CC=C(C=O)C=C1 AVPYQKSLYISFPO-UHFFFAOYSA-N 0.000 claims abstract description 21
- MNWBNISUBARLIT-UHFFFAOYSA-N sodium cyanide Chemical compound [Na+].N#[C-] MNWBNISUBARLIT-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- 239000002994 raw material Substances 0.000 claims abstract description 10
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 5
- 238000002425 crystallisation Methods 0.000 claims abstract description 4
- 230000008025 crystallization Effects 0.000 claims abstract description 4
- 230000020477 pH reduction Effects 0.000 claims abstract description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 69
- 239000000243 solution Substances 0.000 claims description 52
- 239000007788 liquid Substances 0.000 claims description 28
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 claims description 13
- FGUUSXIOTUKUDN-IBGZPJMESA-N C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 Chemical compound C1(=CC=CC=C1)N1C2=C(NC([C@H](C1)NC=1OC(=NN=1)C1=CC=CC=C1)=O)C=CC=C2 FGUUSXIOTUKUDN-IBGZPJMESA-N 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- 239000000463 material Substances 0.000 claims description 4
- 150000007522 mineralic acids Chemical class 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 238000010792 warming Methods 0.000 claims description 4
- YWMLZQYDCHFLMO-UHFFFAOYSA-N chlorobenzene formaldehyde Chemical compound C=O.ClC1=CC=CC=C1 YWMLZQYDCHFLMO-UHFFFAOYSA-N 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 239000012047 saturated solution Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 9
- 230000008676 import Effects 0.000 abstract description 8
- 238000005904 alkaline hydrolysis reaction Methods 0.000 abstract description 2
- 230000036632 reaction speed Effects 0.000 abstract description 2
- MIDPLJHJWQIBNG-UHFFFAOYSA-N [Na].ClC1=CC=C(C(N)C(=O)O)C=C1 Chemical compound [Na].ClC1=CC=C(C(N)C(=O)O)C=C1 MIDPLJHJWQIBNG-UHFFFAOYSA-N 0.000 abstract 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 3
- 238000006150 Bucherer-Bergs reaction Methods 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Natural products NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 3
- 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 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000000155 melt Substances 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 230000001360 synchronised effect Effects 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 2
- WYPWSGOKHITIJT-UHFFFAOYSA-N C(CO)(=O)NC(=O)N.C1=CC=CC=C1 Chemical compound C(CO)(=O)NC(=O)N.C1=CC=CC=C1 WYPWSGOKHITIJT-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- 235000012501 ammonium carbonate Nutrition 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 150000007945 N-acyl ureas Chemical class 0.000 description 1
- 230000000895 acaricidal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- CWFOCCVIPCEQCK-UHFFFAOYSA-N chlorfenapyr Chemical compound BrC1=C(C(F)(F)F)N(COCC)C(C=2C=CC(Cl)=CC=2)=C1C#N CWFOCCVIPCEQCK-UHFFFAOYSA-N 0.000 description 1
- -1 chlorophenyl glycine Chemical compound 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/24—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from hydantoins
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/66—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two 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
- C07D233/72—Two oxygen atoms, e.g. hydantoin
- C07D233/76—Two oxygen atoms, e.g. hydantoin with substituted hydrocarbon radicals attached to the third ring carbon atom
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a kind of preparation methods of p-chlorophenylglycine, are reacted completely in micro passage reaction with 4-chloro-benzaldehyde, ammonium hydrogen carbonate and Cymag, then prepare p-chlorophenylglycine with tubular reactor.Its main feature is that raw material is prepared into intermediate to chlorobenzene glycolylurea through flow gauge by carrying out cyclization in micro passage reaction, intermediate is subjected to alkaline hydrolysis by tubular reactor through flow gauge again and prepares p-chlorophenylglycine sodium, reaction can be completed within 8 18 minutes in total, finally import in reaction bulb and carry out acidification crystallization processing.Product purity is more than 98.0%, and yield is more than 95%.Present invention process route is succinct, and reaction speed is fast, is not only able to improve working efficiency and production capacity, also ensures the production operation safety of technique.
Description
Technical field
The present invention relates to the preparation methods of a kind of medicine, pesticide intermediate p-chlorophenylglycine, and in particular to a kind of to prepare
The method of chlorophenyl glycine.
Background technology
P-chlorophenylglycine is a kind of important organic intermediate, is pesticide aryl-pyrrolidine nitrile insecticidal/acaricidal agent chlorfenapyr
Important intermediate.
At present the country prepare p-chlorophenylglycine method it is very much, it is main to use " Bucherer-Bergs methods ",
Bucherer-Bergs react, and are that carbonyls directly reacts generation second with ammonium carbonate with potassium cyanide and ammonium carbonate or cyanalcohol
The reaction of interior ureide derivative compound.Prepared by raw material and ammonium hydrogen carbonate, Cymag reaction of 4-chloro-benzaldehyde to chlorobenzene glycolylurea
Intermediate, then Basic fluxing raction obtain mixed p-chlorophenylglycine, such as patent CN103086905B.Also document report uses " chlorine
Imitative method " prepares p-chlorophenylglycine, but yield is relatively low with the reaction of 4-chloro-benzaldehyde, chloroform and solid potassium hydroxide through two steps
About 55-60%, such as document Jiangsu Petrochemical Engineering College journal, 1994,6 (2), 31-33.Because both common methods mainly use
Autoclave batch production technique, the period in reaction time is longer, about 8-9h；Technique controlling difficulty is big, product yield is not high and sets
Standby investment is big, cumbersome.
In recent years, micro passage reaction is due in heat transfer, mass transfer, size Control and there is no " enlarge-effects " etc.
Excellent specific property increasingly attracts attention.Corning micro passage reactions are widely used one kind in microreactor.Such as
Fruit this field can make good use of the micro passage reaction of Corning companies, then undoubtedly to the industry
Invention content
It is an object of the invention to use " Bucherer-Bergs methods ", 4-chloro-benzaldehyde, carbonic acid can be made by providing one kind
Hydrogen ammonium and Cymag react completely in micro passage reaction, prepare to chlorobenzene glycolylurea intermediate.Intermediate is not purified directly
Alkaline hydrolysis is carried out, p-chlorophenylglycine is obtained by acidification.The present invention can substantially shorten the reaction time, simplify operating process, into
One step improves the purity and yield of target product p-chlorophenylglycine, and industrial production is suitble to use.
The specific technical solution that the present invention uses is：
A kind of method for preparing p-chlorophenylglycine, this method by reactor include micro passage reaction, microchannel
Reactor includes the preheating zone pipeline communicated from beginning to end successively, mixed zone pipeline, reaction zone pipeline, area's pipeline is quenched, and this method is first
Intermediate material first is prepared to chlorobenzene glycolylurea by micro passage reaction, further prepares p-chlorophenylglycine on this basis, has
Body step includes：
A, prepare raw material：4-chloro-benzaldehyde, ammonium bicarbonate soln, sodium cyanide solution and the sodium hydroxide for preparing liquid are molten
Liquid；
B, preheating zone pipeline is provided with two groups, after being all warming up to 50-60 DEG C of preheating temperature, one group be passed through liquid to chlorobenzene
Formaldehyde, another group each leads into ammonium bicarbonate soln, sodium cyanide solution；
C, the solution of two groups of preheating zone pipelines is all passed through in the pipeline of mixed zone and mixes；
D, the temperature of reaction zone pipeline is warming up to 120-150 DEG C, and mixed solution enters reaction zone from mixed zone pipeline
Ring-closure reaction is carried out in pipeline；
E, the solution after reacting, which enters, to be cooled to 40-60 DEG C area's pipeline is quenched, and carries out obtaining intermediary after reaction is quenched
Confrontation chlorobenzene glycolylurea solution；
F, chlorobenzene glycolylurea solution will not be purified, preparation generation p-chlorophenylglycine is directly reacted with sodium hydroxide solution.
In the step b, 4-chloro-benzaldehyde, Cymag, ammonium hydrogen carbonate molar ratio be 1.0: (1.0-1.5): (1.5-
2.0)。
The step b, the mass flow of the 4-chloro-benzaldehyde of liquid is 5-10g/min；Ammonium hydrogen carbonate saturated solution matter
Amount flow is 20-60g/min；Sodium cyanide solution mass flow is 5-20g/min.
In the step d, when ring-closure reaction is carried out in reaction zone pipeline, solution is used when flowing through reaction zone pipeline to stop
The time stayed is 1-3min.
The step f is realized by the tubular reactor with helical coil line structure, the temperature of tubular reactor
It is 150-170 DEG C to spend, and is mixed what step e was generated containing being passed through tubular reactor with the mixed liquor of sodium hydroxide to chlorobenzene glycolylurea
After carry out Basic fluxing raction, the solution in tubular reactor is exported, be quenched, is acidified to by residence time 7.0-15.0min later
Neutral crystallization obtains p-chlorophenylglycine.
In the step f, the molar ratio to chlorobenzene glycolylurea and sodium hydroxide is 1.0: (2.0-4.0).
The mixed liquor mass flow to chlorobenzene glycolylurea and sodium hydroxide be 25-35g/min, the pipe reaction
Device pipe range 20-30m.
In the step f, the temperature that is quenched of solution is 50-70 DEG C after tubular reactor export.
In the step f, the acidification uses inorganic acid, and the inorganic acid is the concentrated sulfuric acid or dense of concentration 98%
The concentrated hydrochloric acid of degree 36%.
The key of the present invention is using 4-chloro-benzaldehyde, Cymag, ammonium hydrogen carbonate and sodium hydroxide as raw material, using micro- logical
Road reactor and tubular reactor are reacted, and by controlling the technical conditions such as proportioning and flow between each raw material, make main original
Material and the intermediate successively complete reaction in micro passage reaction and tubular reactor, product can be introduced directly into reaction bulb acid
Change crystallization.Reaction process can in a few minutes can the reaction was complete, be greatly shortened the reaction time, save production process, improve
Production capacity.
Equipment is simple used by the method for the present invention, and production operation is easy, improves the security performance of operation.
In short, present invention process route is succinct, reaction speed is fast, is not only able to improve working efficiency and production capacity, also
It ensures the production operation safety of technique, has saved production cost.Pass through the process of the present invention, p-chlorophenylglycine production
Product purity is more than 98.0%, and yield is more than 95.0%.
Description of the drawings
Fig. 1 is the flow diagram of the preparation method of the present invention；
Fig. 2 is the flow diagram of 1,2,3 preparation method of embodiment
Specific embodiment
Below in conjunction with the accompanying drawings and specific embodiment the invention will be further described：
Following embodiment use Corning companies micro passage reaction, use when preparation flow as shown in Figure 1,
The model G1 of micro passage reaction 101, micro passage reaction 101 internal module model include an import, one outlet
G1R*F modules, an import, the G1R*H modules of one outlet and two imports, the G1SHH modules of one outlet, wherein preheating
Area's pipeline 1 includes G1R*F modules in parallel and G1SHH modules, mixed zone pipeline 2 include G1SHH modules, reaction zone pipeline 3 wraps
The G1R*F modules of multiple series connection are included, area's pipeline 4 is quenched and includes G1R*F modules or blocks the G1SHH modules after an import,
As shown in Figure 2.
Tubular reactor 5 is stainless steel pipe dish, and pipe range 20-30m, internal diameter 4mm are placed in the casing equipped with heat medium.
Yield=actually generated in the splicing time in the quality ÷ splicing times of p-chlorophenylglycine theoretical generation to chlorobenzene
The quality of glycine.The content of p-chlorophenylglycine is determined by high performance liquid chromatography external standard method.
Prepare raw material：4-chloro-benzaldehyde needs heating to be allowed to melt rear feeding before the reaction；Ammonium hydrogen carbonate needs to match before the reaction
It is set to 20% aqueous solution；Sodium cyanide solution content is 30%.
Embodiment 1
A, it prepared by chlorobenzene glycolylurea
A) prepare raw material：It prepares and melts the 4-chloro-benzaldehyde feed liquid for liquid, 20% ammonium bicarbonate soln, 30% cyaniding
Sodium solution and 30% sodium hydroxide solution；
B) 4-chloro-benzaldehyde heating is melted after liquid, to be passed through in the G1R*F modules of preheating zone pipeline 1 through metering pump,
Control flow is 5.0g/min, and G1R*F modules preheating temperature is 50 DEG C；
20% ammonium bicarbonate aqueous solution and 30% sodium cyanide solution are passed through preheating zone pipeline 1 simultaneously through metering pump respectively
G1SHH modules are preheated and are mixed, and the flow of 20% ammonium bicarbonate aqueous solution of control is 21.0g/min, 30% sodium cyanide solution
Flow is 5.8g/min, and G1SHH modules preheating temperature is 50 DEG C；
C) 4-chloro-benzaldehyde feed liquid and step b) preheatings and mixed Cymag, ammonium hydrogen carbonate after step a) is preheated
Solution is synchronized to be pumped into mixed zone pipeline 2 and be mixed, and pipeline 2 heating temperature in mixed zone is 120 DEG C, chlorobenzaldehyde, Cymag
Molar ratio with ammonium hydrogen carbonate is 1.0: 1.0: 1.5；
D) mixed liquor obtained through step c) continues through the reaction zone pipe of the G1R*F modules composition including 6 series connection
Road 3, module temperature are 120 DEG C, and the control residence time is 2.6min.
E) area's pipeline 4 is quenched in the feed liquid importing after step d), temperature 60 C carries out that reaction is quenched；
The feed liquid that step e) is obtained exports, and the splicing time is 30min, collects altogether standby to chlorobenzene glycolylurea solution 957.0g
With.
B, the preparation of p-chlorophenylglycine；
F) chlorobenzene glycolylurea solution will not be purified, preparation generation p-chlorophenylglycine is directly reacted with sodium hydroxide solution.
F1) 30% sodium hydroxide solution to chlorobenzene glycolylurea aqueous and 282.7g prepared by 957g is mixed, to chlorine
The molar ratio of benzene glycolylurea and sodium hydroxide is 1.0: 2.0, and the pipe with spiral pipeline structure of 20m long is then passed through through metering pump
In formula reactor 5, control mass flow is 35.0g/min, and reaction temperature is 170 DEG C, and the control residence time is 7.1min.
F2) through step f1) obtained mixed liquor imports and is cooled to 70 DEG C in receiving bottle reaction is quenched, and the splicing time is
35.2min；
F3) by step f2) feed liquid using activated carbon decolorizing, neutralized, generated big with the concentrated sulfuric acid of concentration 98%
The phenylglycine precipitation of amount, filtering drying obtain phenylglycine product 188.8g, content 98.7%, yield 95.3%.
Embodiment 2
A, it prepared by chlorobenzene glycolylurea
A) prepare raw material：It prepares and melts the 4-chloro-benzaldehyde feed liquid for liquid, 20% ammonium bicarbonate soln, 30% cyaniding
Sodium solution and 30% sodium hydroxide solution；
B) 4-chloro-benzaldehyde heating is melted after liquid, to be passed through in the G1R*F modules of preheating zone pipeline 1 through metering pump,
Control flow is 7.5g/min, and G1R*F modules preheating temperature is 55 DEG C；
20% ammonium bicarbonate aqueous solution and 30% sodium cyanide solution are passed through preheating zone pipeline 1 simultaneously through metering pump respectively
G1SHH modules are preheated and are mixed, and the flow of 20% ammonium bicarbonate aqueous solution of control is 35.9g/min, 30% sodium cyanide solution
Flow is 11.3g/min, and G1SHH preheating temperatures are 55 DEG C；
C) 4-chloro-benzaldehyde feed liquid and step b) preheatings and mixed Cymag, ammonium hydrogen carbonate after step a) is preheated
Solution is synchronized to be pumped into mixed zone pipeline 3 and be mixed, and pipeline 3 temperature in mixed zone is 135 DEG C, chlorobenzaldehyde, Cymag and carbon
The molar ratio of sour hydrogen ammonium is 1.0: 1.3: 1.7；
D) mixed liquor obtained through step c) continues through the G1R*F moulds of 6 series connection set in reaction zone pipeline 3
Block, module temperature are 135 DEG C, and the control residence time is 1.5min.
E) the feed liquid importing after step d) is quenched in area's pipeline 4, temperature 50 C carries out that reaction is quenched；
The feed liquid that step e) is obtained exports, and the splicing time is 30min, collects altogether standby to chlorobenzene glycolylurea solution 1640.4g
With.
B, prepared by p-chlorophenylglycine
F) chlorobenzene glycolylurea solution will not be purified, preparation generation p-chlorophenylglycine is directly reacted with sodium hydroxide solution.
F1) by 1640.4 prepared to chlorobenzene glycolylurea aqueous and 640.0 30% sodium hydroxide solution mix, to chlorine
The molar ratio of benzene glycolylurea and sodium hydroxide is 1.0: 3.0, is then passed through in the tubular reactor 5 of 25m long through metering pump, controls matter
Amount flow is 30.0g/min, and reaction temperature is 160 DEG C, and the control residence time is 10.5min.
F2) through step f1) obtained mixed liquor imports and is cooled to 60 DEG C in receiving bottle reaction is quenched, and the splicing time is
76min；
F3) by step f2) feed liquid using activated carbon decolorizing, neutralized, generated big with the concentrated hydrochloric acid of concentration 36%
The phenylglycine precipitation of amount, filtering drying obtain phenylglycine product 283.8g, content 98.2%, yield 95.5%.
Embodiment 3
A, it prepared by chlorobenzene glycolylurea
A) prepare raw material：It prepares and melts the 4-chloro-benzaldehyde feed liquid for liquid, 20% ammonium bicarbonate soln, 30% cyaniding
Sodium solution and 30% sodium hydroxide solution；
B) heat up 4-chloro-benzaldehyde the G1R*F modules melted after liquid, to be passed through through metering pump in preheating zone pipeline 1,
Control flow is 10.0g/min, and G1R*F modules preheating temperature is 60 DEG C；
20% ammonium bicarbonate aqueous solution and 30% sodium cyanide solution are passed through through metering pump in preheating zone pipeline 1 simultaneously respectively
G1SHH modules preheat and mix, the flow of 20% ammonium bicarbonate aqueous solution of control is 56.3g/min, 30% sodium cyanide solution
Flow for 17.4g/min, G1SHH preheating temperatures are 60 DEG C；
C) 4-chloro-benzaldehyde feed liquid and step b) preheatings and mixed Cymag, ammonium hydrogen carbonate after step a) is preheated
Solution is synchronized to be pumped into mixed zone pipeline 2 and be mixed, and pipeline 2 temperature in mixed zone is 120 DEG C, control chlorobenzaldehyde, Cymag
Molar ratio with ammonium hydrogen carbonate is 1.0: 1.5: 2.0；
D) mixed liquor obtained through step c) continues through the reaction zone pipe of the G1R*F modules composition including 6 series connection
Road 3,3 module temperature of reaction zone pipeline are 150 DEG C, and the control residence time is 1min.
E) area's pipeline 4 is quenched in the feed liquid importing after step d), 40 DEG C of temperature carries out that reaction is quenched；
The feed liquid that step e) is obtained exports, and the splicing time is 30min, collects altogether standby to chlorobenzene glycolylurea solution 2510.1g
With.
B, prepared by p-chlorophenylglycine
F) chlorobenzene glycolylurea solution will not be purified, preparation generation p-chlorophenylglycine is directly reacted with sodium hydroxide solution.
F1) 30% sodium hydroxide solution to chlorobenzene glycolylurea aqueous and 1136.0g prepared 2510.1 mixes, right
The molar ratio of chlorobenzene glycolylurea and sodium hydroxide is 1.0: 4.0, is then passed through in the tubular reactor 5 of 30m long through metering pump, is controlled
Mass flow is 25.0g/min, and reaction temperature is 150 DEG C, and the control residence time is 15min.
F2) through step f1) obtained mixed liquor imports and is cooled to 50 DEG C in receiving bottle reaction is quenched, and the splicing time is
145.8min；
F3) by step f2) feed liquid using activated carbon decolorizing, neutralized, generated big with the concentrated sulfuric acid of concentration 98%
The phenylglycine precipitation of amount, filtering drying obtain phenylglycine product 379.2g, content 98.6%, yield 95.9%.
Claims (4)
1. a kind of method for preparing p-chlorophenylglycine, this method by reactor include micro passage reaction (101), it is micro- logical
Road reactor (101) including communicate from beginning to end successively preheating zone pipeline (1), mixed zone pipeline (2), reaction zone pipeline (3), be quenched
Area's pipeline (4), it is characterised in that：This method prepares intermediate material to chlorobenzene glycolylurea by micro passage reaction (101) first,
P-chlorophenylglycine is further prepared on the basis of this, specific steps include：
A, prepare raw material：Prepare 4-chloro-benzaldehyde, ammonium bicarbonate soln, sodium cyanide solution and the sodium hydroxide solution of liquid；
B, preheating zone pipeline (1) is provided with two groups, after being all warming up to 50-60 DEG C of preheating temperature, one group be passed through liquid to chlorobenzene
Formaldehyde, another group each leads into ammonium bicarbonate soln, sodium cyanide solution；
C, the solution of two groups of preheating zone pipelines (1) is all passed through in mixed zone pipeline (2) and mixes；
D, the temperature of reaction zone pipeline (3) is warming up to 120-150 DEG C, and mixed solution enters from mixed zone pipeline (2) to react
Ring-closure reaction is carried out in area's pipeline (3)；
E, the solution after reacting, which enters, to be cooled to 40-60 DEG C and is quenched area's pipeline (4), carries out obtaining intermediate material after reaction is quenched
To chlorobenzene glycolylurea solution；
F, chlorobenzene glycolylurea solution will not be purified, preparation generation p-chlorophenylglycine is directly reacted with sodium hydroxide solution；
The step f is realized by the tubular reactor (5) with helical coil line structure, tubular reactor (5)
Temperature is 150-170 DEG C, by step e generate containing being passed through tubular reactor to the mixed liquor of chlorobenzene glycolylurea and sodium hydroxide
(5) carry out Basic fluxing raction after mixing, residence time 7.0-15.0min, later by tubular reactor (5) solution export,
It is quenched, is acidified to neutral crystallization and obtains p-chlorophenylglycine；
In the step f, the molar ratio to chlorobenzene glycolylurea and sodium hydroxide is 1.0: (2.0-4.0)；
The mixed liquor mass flow to chlorobenzene glycolylurea and sodium hydroxide be 25-35g/min, the tubular reactor pipe
Long 20-30m；
In the step f, the temperature that is quenched of solution is 50-70 DEG C after tubular reactor (5) export；
In the step f, the acidification uses inorganic acid, and the inorganic acid is the concentrated sulfuric acid or concentration of concentration 98%
36% concentrated hydrochloric acid.
2. a kind of method for preparing p-chlorophenylglycine according to claim 1, it is characterised in that：In the step b,
4-chloro-benzaldehyde, Cymag, ammonium hydrogen carbonate molar ratio be 1.0: (1.0-1.5): (1.5-2.0).
3. a kind of method for preparing p-chlorophenylglycine according to claim 1 or 2, it is characterised in that：The step
B, the mass flow of the 4-chloro-benzaldehyde of liquid is 5-10g/min；Ammonium hydrogen carbonate saturated solution mass flow is 20-60g/min；
Sodium cyanide solution mass flow is 5-20g/min.
4. a kind of method for preparing p-chlorophenylglycine according to claim 1, it is characterised in that：In the step d,
When ring-closure reaction is carried out in reaction zone pipeline (3), residence time used is 1- when solution flows through reaction zone pipeline (3)
3min。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610383761.9A CN106083628B (en) | 2016-06-01 | 2016-06-01 | A kind of method for preparing p-chlorophenylglycine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610383761.9A CN106083628B (en) | 2016-06-01 | 2016-06-01 | A kind of method for preparing p-chlorophenylglycine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106083628A CN106083628A (en) | 2016-11-09 |
| CN106083628B true CN106083628B (en) | 2018-06-26 |
Family
ID=57447935
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610383761.9A Active CN106083628B (en) | 2016-06-01 | 2016-06-01 | A kind of method for preparing p-chlorophenylglycine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN106083628B (en) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108623489B (en) * | 2017-03-23 | 2021-02-05 | 重庆紫光川庆化工有限责任公司 | Method for synthesizing glycine by continuously and rapidly alkaline hydrolyzing aminoacetonitrile |
| CN109776424B (en) * | 2019-01-22 | 2022-11-15 | 浙江云涛生物技术股份有限公司 | Novel method for preparing L-phenylglycine precursor phenylhydantoin by using MIC reactor |
| CN109824531B (en) * | 2019-04-02 | 2022-08-23 | 天宝动物营养科技股份有限公司 | Method for continuously and rapidly preparing DL-phenylglycine and analogues thereof |
| CN111470994A (en) * | 2019-10-31 | 2020-07-31 | 上海开荣化工科技有限公司 | Preparation method of p-chlorobenzene glycine |
| CN112174841B (en) * | 2020-11-09 | 2023-02-17 | 唐山晋广化工有限公司 | Production method of p-chlorophenylglycine |
| CN112574049A (en) * | 2020-12-17 | 2021-03-30 | 华阳新材料科技集团有限公司 | Novel method for preparing phenylglycine by using hydrocyanic acid |
| CN113979959A (en) * | 2021-11-20 | 2022-01-28 | 九江中星医药化工有限公司 | Method for continuously and rapidly preparing 1H-tetrazole acetic acid and derivatives thereof |
| CN117964029B (en) * | 2024-03-28 | 2024-06-14 | 内蒙古莱科作物保护有限公司 | Method for preparing p-chlorophenylglycine based on waste liquid generated in production of chlorfenapyr |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104496848A (en) * | 2015-01-15 | 2015-04-08 | 河北诚信有限责任公司 | Method for preparing n-phenylglycinenitrile |
| CN105218401A (en) * | 2015-09-21 | 2016-01-06 | 河北诚信有限责任公司 | The method of continuous processing synthesis benzyl cyanide |
-
2016
- 2016-06-01 CN CN201610383761.9A patent/CN106083628B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104496848A (en) * | 2015-01-15 | 2015-04-08 | 河北诚信有限责任公司 | Method for preparing n-phenylglycinenitrile |
| CN105218401A (en) * | 2015-09-21 | 2016-01-06 | 河北诚信有限责任公司 | The method of continuous processing synthesis benzyl cyanide |
Non-Patent Citations (1)
| Title |
|---|
| Evaluating the one-pot synthesis of hydantoins;Nosrat O. Mahmoodi et al.;《ARKIVOC》;20071231;第29-36页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN106083628A (en) | 2016-11-09 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106083628B (en) | A kind of method for preparing p-chlorophenylglycine | |
| CN101613229B (en) | Improved method for preparing sulfur base fertilizer | |
| CN101254908B (en) | Method for preparing high heat-resistant crystallization II type ammonium polyphosphate | |
| CN106608811A (en) | Method used for preparing chloropropene using microchannel reactors | |
| CN102993034A (en) | Preparation method of methyl-glycine diacetate tri-sodium | |
| CN107628931B (en) | Micro-reaction system and method for synthesizing anisole and derivatives thereof | |
| CN104910031B (en) | The combine production method and device of glycine and hydantoins | |
| CN101107221B (en) | Method for producing imide ether compound | |
| CN111004126A (en) | Preparation method of p-nitrophenol sodium salt | |
| CN108623489A (en) | A method of continuous quickly alkaline hydrolysis aminoacetonitriles synthesizes glycine | |
| CN103194501A (en) | Method for synthetizing chiral cyclic alkyl amino acid by amino transferase | |
| CN105646302B (en) | A kind of production method of methyl mercaptan salt | |
| CN104891462B (en) | Method for synthesising phosphorus oxychloride by virtue of micro-reaction | |
| CN109574918B (en) | Method for continuously preparing 2-chloro-5-chloromethyl pyridine by using microchannel reactor | |
| CN104876876A (en) | Clean production method for continuously synthesizing hydantoin | |
| CN111423392B (en) | Synthesis method of 2-mercapto-6-chlorobenzoxazole | |
| CN101723842B (en) | Method for preparing ethylene diamine tetraacetic acid (EDTA) disodium salt | |
| CN210994311U (en) | Production device for synthesizing imazethapyr by one-step method | |
| CN114105827A (en) | System and method for continuously synthesizing dicyandiamide | |
| CN104974054A (en) | Method and apparatus for preparing iminodiacetic acid by using iminodiacetonitrile to produce mother liquor | |
| CN101417959B (en) | Synthesis method of L-p-nitrophenylalanine | |
| CN113968792A (en) | Novel method for synthesizing 2-chloro-5-aminophenol | |
| CN217140330U (en) | Device for continuously producing hydantoin by fixed bed reactor | |
| CN109912439A (en) | A kind of method that cyanalcohol method continuously quickly prepares DL- phenylglycine and the like | |
| CN100365071C (en) | Method for producing idigo by cyclic utilization of non-reacted raw materials |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Liu Shaohua Inventor after: Shen Shigang Inventor after: Wang Xiaolong Inventor after: Guo Yayun Inventor after: Zhang Chenliang Inventor before: Liu Shaohua Inventor before: Shi Hui Inventor before: Wang Xiaolong Inventor before: Guo Yayun Inventor before: Zhang Jing |
|
| TA01 | Transfer of patent application right |
Effective date of registration: 20171123 Address after: Shijiazhuang City, Hebei province 051130 yuan Yuanshi County, Zhao Lunan Applicant after: Hebei Chengxin Co., Ltd. Applicant after: Hebei University Address before: Shijiazhuang City, Hebei province 051130 yuan Yuanshi County, Zhao Lunan Applicant before: Hebei Chengxin Co., Ltd. |
|
| TA01 | Transfer of patent application right | ||
| TA01 | Transfer of patent application right |
Effective date of registration: 20180321 Address after: 071002 East Road, Hebei, Baoding No. 54 Applicant after: Hebei University Applicant after: Hebei Chengxin Co., Ltd. Address before: Shijiazhuang City, Hebei province 051130 yuan Yuanshi County, Zhao Lunan Applicant before: Hebei Chengxin Co., Ltd. Applicant before: Hebei University |
|
| TA01 | Transfer of patent application right | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CP01 | Change in the name or title of a patent holder | ||
| CP01 | Change in the name or title of a patent holder |
Address after: No. 180, 54 East Road, Baoding, Hebei Province Co-patentee after: Hebei Chengxin Group Co., Ltd. Patentee after: Hebei University Address before: No. 180, 54 East Road, Baoding, Hebei Province Co-patentee before: Hebei Chengxin Co., Ltd. Patentee before: Hebei University |
|
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20190426 Address after: 750336 North End of Lantai Avenue, Ustin Town, Alxa League Economic Development Zone, Inner Mongolia Autonomous Region Patentee after: Inner Mongolia integrity Yong'an Chemical Co., Ltd. Address before: No. 180, 54 East Road, Baoding, Hebei Province Co-patentee before: Hebei Chengxin Group Co., Ltd. Patentee before: Hebei University |