CN117586261A - Efficient environment-friendly guanine continuous synthesis process and device - Google Patents
Efficient environment-friendly guanine continuous synthesis process and device Download PDFInfo
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- CN117586261A CN117586261A CN202311500674.3A CN202311500674A CN117586261A CN 117586261 A CN117586261 A CN 117586261A CN 202311500674 A CN202311500674 A CN 202311500674A CN 117586261 A CN117586261 A CN 117586261A
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- guanine
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- hydrochloric acid
- water
- formamide
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- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 title claims abstract description 294
- 238000000034 method Methods 0.000 title claims abstract description 53
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 41
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 224
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims abstract description 116
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 80
- 238000006243 chemical reaction Methods 0.000 claims abstract description 76
- 239000012043 crude product Substances 0.000 claims abstract description 61
- 239000000243 solution Substances 0.000 claims abstract description 57
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 28
- 238000003756 stirring Methods 0.000 claims abstract description 28
- 238000000967 suction filtration Methods 0.000 claims abstract description 28
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims abstract description 26
- 239000000725 suspension Substances 0.000 claims abstract description 26
- 239000000047 product Substances 0.000 claims abstract description 21
- 239000000203 mixture Substances 0.000 claims abstract description 20
- 239000010413 mother solution Substances 0.000 claims abstract description 18
- SWELIMKTDYHAOY-UHFFFAOYSA-N 2,4-diamino-6-hydroxypyrimidine Chemical compound NC1=CC(=O)N=C(N)N1 SWELIMKTDYHAOY-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 16
- 238000006170 formylation reaction Methods 0.000 claims abstract description 15
- 239000003054 catalyst Substances 0.000 claims abstract description 13
- 235000010288 sodium nitrite Nutrition 0.000 claims abstract description 13
- 238000001704 evaporation Methods 0.000 claims abstract description 12
- 238000002156 mixing Methods 0.000 claims abstract description 7
- 239000012452 mother liquor Substances 0.000 claims description 69
- 238000010438 heat treatment Methods 0.000 claims description 40
- 239000002351 wastewater Substances 0.000 claims description 30
- IBAOFQIOOBQLHE-UHFFFAOYSA-N 2-amino-3,9-dihydropurin-9-ium-6-one;chloride Chemical compound Cl.N1C(N)=NC(=O)C2=C1N=CN2 IBAOFQIOOBQLHE-UHFFFAOYSA-N 0.000 claims description 25
- 238000001914 filtration Methods 0.000 claims description 21
- 238000004821 distillation Methods 0.000 claims description 19
- 239000000706 filtrate Substances 0.000 claims description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 18
- 150000003863 ammonium salts Chemical class 0.000 claims description 18
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 16
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 16
- 238000001816 cooling Methods 0.000 claims description 16
- 238000007670 refining Methods 0.000 claims description 12
- 238000006297 dehydration reaction Methods 0.000 claims description 11
- 238000011010 flushing procedure Methods 0.000 claims description 11
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 230000003472 neutralizing effect Effects 0.000 claims description 9
- 238000011084 recovery Methods 0.000 claims description 9
- 238000004065 wastewater treatment Methods 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 claims description 5
- 239000000110 cooling liquid Substances 0.000 claims description 4
- 230000002194 synthesizing effect Effects 0.000 claims description 4
- 238000004321 preservation Methods 0.000 claims description 3
- 229910052979 sodium sulfide Inorganic materials 0.000 claims description 3
- GRVFOGOEDUUMBP-UHFFFAOYSA-N sodium sulfide (anhydrous) Chemical compound [Na+].[Na+].[S-2] GRVFOGOEDUUMBP-UHFFFAOYSA-N 0.000 claims description 3
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 3
- 235000019345 sodium thiosulphate Nutrition 0.000 claims description 3
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 239000002699 waste material Substances 0.000 abstract description 2
- 238000001514 detection method Methods 0.000 description 20
- 239000007791 liquid phase Substances 0.000 description 20
- 230000002572 peristaltic effect Effects 0.000 description 13
- 238000001035 drying Methods 0.000 description 10
- 239000012535 impurity Substances 0.000 description 10
- 238000005303 weighing Methods 0.000 description 10
- 238000007034 nitrosation reaction Methods 0.000 description 9
- 230000014759 maintenance of location Effects 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 230000001276 controlling effect Effects 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 238000000746 purification Methods 0.000 description 5
- 230000001502 supplementing effect Effects 0.000 description 5
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000009935 nitrosation Effects 0.000 description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 238000010924 continuous production Methods 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000022244 formylation Effects 0.000 description 2
- 229960000789 guanidine hydrochloride Drugs 0.000 description 2
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 229940075420 xanthine Drugs 0.000 description 2
- SYEYEGBZVSWYPK-UHFFFAOYSA-N 2,5,6-triamino-4-hydroxypyrimidine Chemical compound NC1=NC(N)=C(N)C(O)=N1 SYEYEGBZVSWYPK-UHFFFAOYSA-N 0.000 description 1
- HVMRLFSFHWCUCG-UHFFFAOYSA-N 2,6-diamino-5-nitroso-1h-pyrimidin-4-one Chemical compound NC1=NC(=O)C(N=O)=C(N)N1 HVMRLFSFHWCUCG-UHFFFAOYSA-N 0.000 description 1
- MGWGWNFMUOTEHG-UHFFFAOYSA-N 4-(3,5-dimethylphenyl)-1,3-thiazol-2-amine Chemical compound CC1=CC(C)=CC(C=2N=C(N)SC=2)=C1 MGWGWNFMUOTEHG-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- NDEMNVPZDAFUKN-UHFFFAOYSA-N guanidine;nitric acid Chemical compound NC(N)=N.O[N+]([O-])=O.O[N+]([O-])=O NDEMNVPZDAFUKN-UHFFFAOYSA-N 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- ANGDWNBGPBMQHW-UHFFFAOYSA-N methyl cyanoacetate Chemical compound COC(=O)CC#N ANGDWNBGPBMQHW-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/18—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 one oxygen and one nitrogen atom, e.g. guanine
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0006—Controlling or regulating processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0006—Controlling or regulating processes
- B01J19/0013—Controlling the temperature of the process
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/24—Stationary reactors without moving elements inside
- B01J19/2415—Tubular reactors
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J4/00—Feed or outlet devices; Feed or outlet control devices
- B01J4/001—Feed or outlet devices as such, e.g. feeding tubes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2204/00—Aspects relating to feed or outlet devices; Regulating devices for feed or outlet devices
- B01J2204/002—Aspects relating to feed or outlet devices; Regulating devices for feed or outlet devices the feeding side being of particular interest
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00002—Chemical plants
- B01J2219/00027—Process aspects
- B01J2219/0004—Processes in series
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00049—Controlling or regulating processes
- B01J2219/00051—Controlling the temperature
- B01J2219/00074—Controlling the temperature by indirect heating or cooling employing heat exchange fluids
- B01J2219/00087—Controlling the temperature by indirect heating or cooling employing heat exchange fluids with heat exchange elements outside the reactor
- B01J2219/00099—Controlling the temperature by indirect heating or cooling employing heat exchange fluids with heat exchange elements outside the reactor the reactor being immersed in the heat exchange medium
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention discloses a high-efficiency environment-friendly continuous guanine synthesis process and device, comprising the following steps of: uniformly mixing 2, 4-diamino-6-hydroxypyrimidine, sodium nitrite and first water to obtain a suspension; introducing the suspension and the first hydrochloric acid solution into a pipeline for mixed reaction, and injecting the reaction solution into a reaction bottle for continuous stirring; after all the reaction liquid in the pipeline is injected into the reaction bottle, continuing stirring to uniformly mix the reaction liquid, and then evaporating to remove water until no water is distilled; and adding formamide and a catalyst into a reaction bottle, sequentially carrying out formylation reaction and cyclization reaction, and then carrying out suction filtration to obtain a guanine crude product and a formamide mother solution. The invention has the advantages of short process flow, safe and controllable reaction, capability of reducing three wastes, high purity of guanine finished products, high reaction yield, and high purity of guanine finished products of more than 99.6 percent, and the total yield of guanine finished products obtained by reaction of more than 89 percent.
Description
Technical Field
The invention relates to the technical field of guanine production, in particular to a high-efficiency environment-friendly continuous guanine synthesis process and device.
Background
In the existing guanine production process, methyl cyanoacetate is mainly used as a starting material and cyclized with guanidine hydrochloride or guanidine nitrate to obtain 2, 4-diamino-6-hydroxypyrimidine; nitrosation with sodium nitrite in an acidic medium to obtain 2, 4-diamino-5-nitroso-6-hydroxypyrimidine; then using a metal catalyst, introducing hydrogen to reduce nitroso to obtain 2,4, 5-triamino-6-hydroxypyrimidine, and reacting with sulfuric acid to form relatively stable sulfate; finally heating and cyclization in formamide or formic acid to obtain guanine crude product. The process has long flow, complex reaction, high risk processes such as nitrosation and hydrogenation, metal catalysts, liquid alkali, sulfuric acid and formic acid, high treatment difficulty of byproducts and wastewater, high production cost and high environmental protection cost. In addition, the acid and nitrite used in the nitrosation reaction are severely excessive, which can lead to increased impurities in subsequent reactions. To obtain guanine with high purity, the nitrosate must be purified before proceeding to the next process. Therefore, high-purity guanine cannot be obtained by a continuous production process in the prior art.
Disclosure of Invention
The invention aims to overcome the technical defects, and provides a high-efficiency environment-friendly continuous guanine synthesis process and device, which solve the technical problem that high-purity guanine cannot be obtained through a continuous process in the prior art.
In a first aspect, the invention provides a high-efficiency environment-friendly guanine continuous synthesis process, which comprises the following steps:
s100, synthesizing a guanine crude product; optionally, the composition may be in the form of a gel,
s200, recovering formamide mother liquor;
s300, refining a guanine crude product;
wherein, the steps of guanine crude product synthesis include:
s101, uniformly mixing 2, 4-diamino-6-hydroxypyrimidine, sodium nitrite and first water to obtain a suspension;
s102, introducing the suspension and the first hydrochloric acid solution into a pipeline for mixed reaction, and injecting the reaction solution into a reaction bottle for continuous stirring;
s103, after all the reaction liquid in the pipeline is injected into the reaction bottle, continuing stirring to uniformly mix the reaction liquid, and then evaporating to remove water until no water is distilled;
s104, adding formamide and a catalyst into a reaction bottle, sequentially carrying out formylation reaction at 100-160 ℃ and cyclization reaction at 160-175 ℃, and carrying out suction filtration to obtain guanine crude product and formamide mother liquor.
In a second aspect, the invention provides a high-efficiency environment-friendly guanine continuous synthesis device, which comprises a pipeline and a reaction bottle which are sequentially communicated;
the efficient and environment-friendly guanine continuous synthesis device is used for executing the efficient and environment-friendly guanine continuous synthesis process provided by the first aspect of the invention.
Compared with the prior art, the invention has the beneficial effects that:
the invention has the advantages of short process flow, safe and controllable reaction, reduced originally required dangerous process, no use of metal catalyst, liquid alkali, sulfuric acid and formic acid, reduced three wastes, high purity of guanine finished products, high reaction yield, purity of guanine finished products being more than 99.6 percent, and total yield of guanine finished products being more than 89 percent.
Drawings
FIG. 1 is a schematic diagram of an embodiment of a high-efficiency, environmentally friendly guanine continuous synthesis system provided by the present invention;
FIG. 2 is a graph showing the liquid phase detection data of guanine (fresh hydrochloric acid) obtained in example 1 of the present invention;
FIG. 3 is a graph showing the liquid phase detection data of guanine (mother liquor of hydrochloric acid) obtained in example 1 of the present invention;
FIG. 4 is a graph showing the liquid phase detection data of guanine (fresh hydrochloric acid) obtained in example 2 of the present invention;
FIG. 5 is a graph showing the liquid phase detection data of guanine (mother liquor of hydrochloric acid) obtained in example 2 of the present invention;
FIG. 6 is a graph showing the liquid phase detection data of guanine (fresh hydrochloric acid) obtained in example 3 of the present invention;
FIG. 7 shows liquid phase detection data of guanine (mother liquor of hydrochloric acid) obtained in example 3 of the present invention;
FIG. 8 is a graph showing the liquid phase detection data of guanine (fresh hydrochloric acid) obtained in example 4 of the present invention;
FIG. 9 is a graph showing the liquid phase detection data of guanine (mother liquor of hydrochloric acid) obtained in example 4 of the present invention;
FIG. 10 is a graph showing the liquid phase detection data of guanine (fresh hydrochloric acid) obtained in example 5 of the present invention;
FIG. 11 shows liquid phase detection data of guanine (mother liquor of hydrochloric acid) obtained in example 5 of the present invention.
Detailed Description
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
In a first aspect, the invention provides a high-efficiency environment-friendly guanine continuous synthesis process, which comprises the following steps: s100, synthesizing a guanine crude product; and optionally, S200, recovery of the carboxamide mother liquor; s300, refining the guanine crude product.
In this embodiment, the steps for synthesizing the guanine crude product include:
s101, uniformly mixing 2, 4-diamino-6-hydroxypyrimidine, sodium nitrite and first water to obtain a suspension;
s102, introducing the suspension and the first hydrochloric acid solution into a pipeline for mixed reaction, and injecting the reaction solution into a reaction bottle for continuous stirring;
s103, after all the reaction liquid in the pipeline is injected into the reaction bottle, continuing stirring to uniformly mix the reaction liquid, and then evaporating to remove water until no water is distilled;
s104, adding formamide and a catalyst into a reaction bottle, sequentially carrying out formylation reaction at 100-160 ℃ and cyclization reaction at 160-175 ℃, and carrying out suction filtration to obtain guanine crude product and formamide mother liquor.
As is known to those skilled in the art, the nitrosation reaction is strongly exothermic and tends to cause instability of the system. According to the invention, the suspension containing 2, 4-diamino-6-hydroxypyrimidine, sodium nitrite and first water and the first hydrochloric acid solution are introduced into a pipeline in advance for mixed reaction, so that the mass and heat transfer efficiency is increased, the nitrosation reaction is more stable and controllable, and the hydrogenation process is omitted; when the reaction liquid is discharged out of the pipeline, the nitrosation reaction is basically finished, a reaction bottle is used for receiving nitrosation products and carrying out the next reaction, the heat release is not obvious after the reaction liquid enters the reaction bottle, and the reaction bottle does not need to control the temperature; however, after the reaction liquid enters the reaction bottle, materials are uniformly mixed by continuous stirring, so that the situation that the raw materials are entrapped and do not participate in the reaction due to the subsequent reaction caused by direct heating is avoided. In addition, the inventor finds that if evaporation and water removal are not carried out before the formylation reaction, the formylation reaction is too severe, a large amount of gas is generated, and flushing is caused, so that the reaction cannot be smoothly carried out, and finally continuous synthesis of guanine cannot be realized. It can be seen that the process of the invention reduces the risk of reaction and allows for continuous production.
In the step S101, the mass ratio of the 2, 4-diamino-6-hydroxypyrimidine to sodium nitrite to the first water is 1: (0.5-0.7): (7.5-11).
In the step S102, the mass fraction of the first hydrochloric acid solution is 30% -35%, and the dosage ratio of the 2, 4-diamino-6-hydroxypyrimidine to the first hydrochloric acid solution is 1g: (3-5) mL.
In the step S102, the inner diameter of the pipeline is 2-20 mm, more preferably 4-15 mm, still more preferably 4-10 mm; the length of the pipeline is 5-20 m, and further 10-15 m.
In step S102, the flow rate of the suspension into the pipeline is 15-20 mL/min, and the flow rate of the first hydrochloric acid solution into the pipeline is 5-10 mL/min. Too high a flow rate will cause the reactants to solidify and clog the pipeline just after mixing, and too low a flow rate will result in too long a reaction time.
In step S102, the suspension and the first hydrochloric acid solution are introduced into a pipeline by a peristaltic pump to perform a mixing reaction.
In step S102, when the suspension and the first hydrochloric acid solution are mixed in the pipeline, the pipeline is soaked in cold water at 0-20 ℃ so as to further increase the heat and mass transfer efficiency, and the nitrosation reaction which originally emits a large amount of heat and nitrogen dioxide becomes safer and more controllable.
In step S103, in the process of evaporating water, the temperature is raised to 100 ℃ and evaporated until no water is distilled off or only a very small amount of water is distilled off. In the process of evaporating and removing water, the water cannot be completely evaporated due to the existence of a large amount of nitrosation products, so that the water is evaporated until no water is distilled or only a very small amount of water is distilled.
In step S104, the catalyst is at least one of sodium sulfide, sodium thiosulfate or sodium dithionite. Compared with other common catalysts, the catalyst is more beneficial to reducing impurities in guanine crude products and improving guanine purity.
In step S104, the mass ratio of the 2, 4-diamino-6-hydroxypyrimidine to the formamide to the catalyst is 1: (5-7): (0.1-0.2).
In step S104, the temperature is raised from 100 ℃ to 160 ℃ at a heating rate of 0.1-0.3 ℃/min in the process of formylation, the formylation must be slowly raised to prevent flushing, and the total time of the whole heating stage and the heat preservation stage is 4-6 h; in the process of the cyclization reaction, the temperature is raised from 160 ℃ to 175 ℃ at a heating rate of 0.1-0.5 ℃/min, the heating rate of the high Wen Huange reaction can be properly accelerated, and the total time of the whole heating stage and the heat preservation stage is 3-5 h.
Wherein the cyclization reaction is a cyclization reflux reaction or a cyclization dehydration reaction, preferably a cyclization dehydration reaction. The inventor further found in the experimental process that compared with the cyclization reaction in a reflux way, the method provided by the invention is more beneficial to improving the purity of the guanine crude product through the cyclization dehydration reaction.
In this embodiment, the step of recovering the formamide mother solution includes:
s201, performing first reduced pressure distillation on the formamide mother liquor obtained after suction filtration in the step S104 through a water pump to obtain a front fraction with ammonia water as a main component;
s202, performing second reduced pressure distillation on the formamide mother liquor subjected to the first reduced pressure distillation through an oil pump, and recovering formamide.
In the first reduced pressure distillation process, the temperature is firstly increased to 110-130 ℃ to start reduced pressure distillation, and the temperature is continuously increased to 140-160 ℃ until no fraction is distilled out.
In the second reduced pressure distillation process, the temperature is firstly increased to 80-100 ℃ to start reduced pressure distillation, and the temperature is continuously increased to 120-140 ℃ until no fraction is distilled out.
After the first reduced pressure distillation, the temperature must be reduced before the oil pump is replaced, so that formamide is prevented from being sucked into the oil pump, and the recovery rate is reduced.
Wherein the receiver is also replaced before the second reduced pressure distillation, avoiding the recovered formamide from mixing with the front cut.
Wherein, the temperature of the cooling liquid introduced into the condensing tube jacket is 10-20 ℃ in the process of the first reduced pressure distillation, and the temperature of the cooling liquid introduced into the condensing tube jacket is 5-10 ℃ in the process of the second reduced pressure distillation. Ammonia water is the main component of the front fraction, ammonia gas with too high jacket temperature escapes from the water, has strong odor, has too low temperature and high energy consumption, and can solidify the fraction in the jacket; the second reduced pressure distillation replaces an oil pump with higher vacuum degree, and when the temperature is too high, formamide cannot be liquefied and collected to be sucked into the pump, the pump body is damaged, the recovery rate is reduced, and the formamide is possibly solidified in the jacket when the temperature is too low.
Wherein, the recovered formamide in step S202 can be used for the reaction in step S104, and a certain amount of new formamide is added when the reaction is insufficient.
In this embodiment, the steps of purifying the guanine crude product include:
s301, adding the guanine crude product into a second hydrochloric acid solution, and fully dissolving the guanine crude product into a dark brown clear solution;
s302, adding active carbon into dark brown clear liquid, stirring and decoloring, and then filtering while the mixture is hot, cooling and suction-filtering filtrate to obtain guanine hydrochloride and hydrochloric acid mother liquor;
s303, dissolving guanine hydrochloride into second water, then adjusting the pH value to 6-8 by ammonia water, and obtaining a guanine finished product through suction filtration.
The invention further improves the purity of guanine by adding secondary refining to remove impurities.
Wherein the mass fraction of the second hydrochloric acid solution is 7% -10%; the dosage ratio of the guanine crude product to the second hydrochloric acid solution is 1g: (10-20) mL.
Wherein, in the process of fully dissolving the guanine crude product into dark brown clear solution, the guanine crude product needs to be heated to 80-90 ℃.
Wherein the dosage ratio of the activated carbon to the dark brown clarified liquid is (0.01-0.03) g:1mL, further (0.015-0.03) g:1mL.
Wherein the temperature of stirring and decoloring is not more than 90 ℃, further 80-90 ℃, and the time of stirring and decoloring is 20-40 min. In the process of stirring and decoloring, the content of the impurity xanthine can be increased due to the excessively high temperature or excessively long decoloring time.
Wherein the temperature of the filtrate after cooling is 10-20 ℃.
Wherein, the hydrochloric acid mother solution can be used for refining guanine crude products in other batches. The invention is favorable for improving the yield of guanine by applying hydrochloric acid mother liquor. When the solution can not be dissolved into dark brown clear solution, a proper amount of hydrochloric acid mother solution or concentrated hydrochloric acid can be added. However, if the acidity of the hydrochloric acid mother solution is more than 20%, the hydrochloric acid mother solution can not be continuously used, and if the hydrochloric acid mother solution is continuously used, the final finished product has high xanthine content.
Wherein, the mass ratio of guanine hydrochloride to second water is 1: (5-20).
Wherein, in the process of dissolving guanine hydrochloride in the second water, the guanine hydrochloride needs to be heated to 50-60 ℃.
In this embodiment, the efficient and environment-friendly continuous guanine synthesis process further includes: s400, wastewater treatment is performed to recover ammonium salt.
Wherein, the step of reclaiming ammonium salt in wastewater treatment comprises the following steps: and (3) neutralizing hydrochloric acid mother liquor in the step (302) by using the alkaline wastewater distilled in the step (S104) and/or the alkaline wastewater generated by flushing the water diversion device, regulating the pH to 6-8, and then filtering, concentrating, cooling and crystallizing to obtain ammonium salt.
In the formylation reaction process, formamide can be decomposed to generate ammonia and carbon dioxide under the conditions of first water, alkali and high temperature, and ammonium salt is further formed; when the cyclization reaction is a cyclization dehydration reaction, water is also distilled out; the ammonium salt is carried out by the water distilled out in S104 to form alkaline waste water. The ammonium salt formed by neutralizing the hydrochloric acid mother solution with the alkaline wastewater can be used for the synthesis reaction of guanidine hydrochloride.
Wherein, in the process of neutralizing hydrochloric acid mother liquor by the alkaline waste water distilled out in the step S104 and/or the alkaline waste water generated by the flushing water diversion device, when the alkaline waste water is insufficient, ammonia water can be supplemented.
The hydrochloric acid mother solution is hydrochloric acid mother solution with concentration of more than 20% in the step S302, which can not be continuously used, so that high-value utilization of alkaline wastewater and the hydrochloric acid mother solution is realized.
Referring to fig. 1, in a second aspect, the present invention provides a high-efficiency environment-friendly guanine continuous synthesis apparatus, which includes a pipeline 1 and a reaction bottle 2 that are sequentially connected;
the efficient and environment-friendly guanine continuous synthesis device is used for executing the efficient and environment-friendly guanine continuous synthesis process provided by the first aspect of the invention.
In this embodiment, the feeding end of the pipeline 1 is communicated with the suspension storage tank 5 through the first peristaltic pump 3, and the feeding end of the pipeline 1 is communicated with the hydrochloric acid storage tank 6 through the second peristaltic pump 4, so that the suspension and the first hydrochloric acid solution are introduced into the pipeline 1 for reaction.
In the present embodiment, the pipe 1 is immersed in a cold water tank so as to cool the pipe 1.
Example 1
A high-efficiency environment-friendly guanine continuous synthesis process comprises the following steps:
(1) And (3) guanine crude product synthesis: 50 g of 2, 4-diamino-6-hydroxypyrimidine and 30 g of sodium nitrite are added into 450mL of water to prepare suspension; the peristaltic pump flow rate of the injected suspension is set to be 15mL/min, the peristaltic pump flow rate of the injected 35% hydrochloric acid is set to be 5mL/min, the two solutions are led into a pipeline (the inner diameter of the pipeline is 6mm and the length of the pipeline is 10 m) soaked in cold water at 20 ℃ for mixed reaction, and the reaction solution is injected into a reaction bottle and stirred continuously; after all the reaction liquid in the pipeline is injected into the reaction bottle, stirring is fully carried out for 30 minutes, the temperature is raised to 100 ℃ for evaporation and water removal until no water is distilled; 330 g of formamide and 10 g of sodium sulfide are added, the temperature is gradually increased to 160 ℃ for formylation reaction, the temperature increasing time is controlled to be 4 hours, and the temperature is kept for 1 hour; continuously heating to 175 ℃ to carry out cyclization dehydration reaction, controlling the heating time to be 1 hour, preserving heat for 3 hours, and carrying out suction filtration to obtain guanine crude products and formamide mother liquor;
(2) Recovering formamide mother liquor: 175.3 g of formamide mother liquor is distilled under reduced pressure by a water pump at 120 ℃, and the temperature is continuously increased to 150 ℃ until no fraction is distilled out, and the front fraction is 15 g; the receiver was replaced again, formamide was distilled off under reduced pressure at 90℃with an oil pump, and the temperature was continuously raised to 130℃until no more fraction was distilled off, and 153 g of formamide was recovered.
(3) Guanine crude purification (fresh hydrochloric acid): adding 900mL of 8% hydrochloric acid and the guanine crude product obtained in the step (1) into a reactor, heating to 90 ℃ to fully dissolve the guanine crude product into dark brown clear solution, adding 13.5 g of active carbon, stirring and decoloring for 30 minutes; and filtering while the mixture is hot, cooling the filtrate to 10 ℃, and carrying out suction filtration to obtain guanine hydrochloride and hydrochloric acid mother liquor.
(4) Guanine crude product refining (hydrochloric acid mother liquor is used for application): adding the hydrochloric acid mother solution and another batch of guanine crude product obtained in the step (1) into a reactor, and heating to 90 ℃, wherein the guanine crude product is not fully dissolved into dark brown clear solution; adding 30mL of hydrochloric acid, fully dissolving to obtain dark brown clear solution, adding 13.5 g of active carbon, stirring and decoloring for 30 minutes; and then filtering while the mixture is hot, cooling the filtrate to 10 ℃, and carrying out suction filtration to obtain guanine hydrochloride (after hydrochloric acid mother liquor is applied) and hydrochloric acid mother liquor.
Adding 800mL of water into 2 batches of guanine hydrochlorides in the step (3) and the step (4), heating to 50 ℃, adjusting the pH to 7 by ammonia water, carrying out suction filtration to obtain a guanine finished product, drying and weighing 52.5 g of the previous batch, and obtaining 99.94% of purity; the latter batch was 56.7 g with a purity of 99.95%.
(5) And (3) wastewater treatment and ammonium salt recovery: and collecting alkaline wastewater distilled in the reaction, combining the alkaline wastewater with alkaline wastewater of a flushing water diversion device, neutralizing hydrochloric acid mother liquor, supplementing ammonia water, adjusting the pH value to 7, filtering insoluble impurities, concentrating filtrate to obtain ammonium salt, and weighing 122.5 g after drying.
TABLE 1 liquid phase detection data for guanine (fresh hydrochloric acid) obtained in example 1
| Retention time | Area of | Area percent | Peak height | Theoretical plate number |
| 3.206 | 0.62 | 0.00 | 0.13 | 4733 |
| 4.753 | 0.88 | 0.01 | 0.16 | 8960 |
| 10.634 | 16280.00 | 99.94 | 1121.32 | 12262 |
| 13.543 | 4.35 | 0.03 | 0.24 | 12696 |
| 17.998 | 4.70 | 0.02 | 0.21 | 15593 |
| Totals to | 16290.55 | 100.00 |
TABLE 2 liquid phase detection data for guanine (mother liquor with hydrochloric acid) obtained in example 1
| Retention time | Area of | Area percent | Peak height | Theoretical plate number |
| 3.202 | 0.61 | 0.00 | 0.13 | 13089 |
| 4.752 | 1.11 | 0.01 | 0.18 | 9028 |
| 4.918 | 1.35 | 0.01 | 0.19 | 9412 |
| 10.599 | 13846.06 | 99.95 | 984.72 | 13090 |
| 13.540 | 3.85 | 0.03 | 0.20 | 10926 |
| Totals to | 13852.99 | 100.00 |
Example 2
A high-efficiency environment-friendly guanine continuous synthesis process comprises the following steps:
(1) And (3) guanine crude product synthesis: 50 g of 2, 4-diamino-6-hydroxypyrimidine and 35 g of sodium nitrite are added into 400mL of water to prepare suspension; the peristaltic pump flow rate for injecting the suspension is set to be 20mL/min, the peristaltic pump flow rate for injecting the 33% hydrochloric acid to be 180mL is set to be 9mL/min, the two solutions are led into a pipeline (the inner diameter of the pipeline is 6mm and the length of the pipeline is 15 m) soaked in cold water at the temperature of 10 ℃ for mixed reaction, and the reaction solution is injected into a reaction bottle and stirred continuously; after all the reaction liquid in the pipeline is injected into the reaction bottle, stirring is fully carried out for 30 minutes, the temperature is raised to 100 ℃ for evaporation and water removal until no water is distilled; adding 350 g of formamide and 10 g of sodium thiosulfate, gradually heating to 160 ℃ to perform formylation reaction, controlling the heating time to be 4 hours, and preserving the heat for 1 hour; continuously heating to 175 ℃ to carry out cyclization dehydration reaction, controlling the heating time to be 1 hour, preserving heat for 3 hours, and carrying out suction filtration to obtain guanine crude products and formamide mother liquor;
(2) Recovering formamide mother liquor: 205.3 g of formamide mother liquor is distilled under reduced pressure by a water pump at 120 ℃ and is continuously heated to 150 ℃ until no fraction is distilled out, and 16 g of front fraction is obtained; the receiver was replaced again, formamide was distilled off under reduced pressure at 90℃with an oil pump, and the temperature was continuously raised to 130℃until no more fraction was distilled off, and 183 g of formamide was recovered.
(3) Guanine crude purification (fresh hydrochloric acid): 1000mL of hydrochloric acid with the concentration of 7% and the guanine crude product obtained in the step (1) are put into a reactor and heated to 90 ℃ to be fully dissolved into dark brown clear solution, 15 g of activated carbon is added, and the mixture is stirred and decolorized for 30 minutes; and filtering while the mixture is hot, cooling the filtrate to 15 ℃, and carrying out suction filtration to obtain guanine hydrochloride and hydrochloric acid mother liquor.
(4) Guanine crude product refining (hydrochloric acid mother liquor is used for application): adding the hydrochloric acid mother solution and another batch of guanine crude product obtained in the step (1) into a reactor, and heating to 90 ℃, wherein the guanine crude product is not fully dissolved into dark brown clear solution; adding 35mL of hydrochloric acid, fully dissolving to obtain dark brown clear solution, adding 15 g of active carbon, and stirring for decolorizing for 30 minutes; and then filtering while the mixture is hot, cooling the filtrate to 15 ℃, and carrying out suction filtration to obtain guanine hydrochloride (after hydrochloric acid mother liquor is applied) and hydrochloric acid mother liquor.
Adding 700mL of water into 2 batches of guanine hydrochlorides in the step (3) and the step (4), heating to 50 ℃, adjusting the pH to 7 by ammonia water, carrying out suction filtration to obtain a guanine finished product, drying and weighing 51.9 g of the former batch, and obtaining 99.94% of purity; the latter batch was 57.9 g with a purity of 99.95%.
(5) And (3) wastewater treatment and ammonium salt recovery: and collecting alkaline wastewater distilled in the reaction, combining the alkaline wastewater with alkaline wastewater of a flushing water diversion device, neutralizing hydrochloric acid mother liquor, supplementing ammonia water, adjusting the pH value to 7, filtering insoluble impurities, concentrating filtrate to obtain ammonium salt, and weighing 120.8 g after drying.
TABLE 3 liquid phase detection data for guanine (fresh hydrochloric acid) obtained in example 2
| Retention time | Area of | Area percent | Peak height | Theoretical plate number |
| 3.199 | 0.70 | 0.00 | 0.15 | 13515 |
| 4.752 | 0.89 | 0.005 | 0.17 | 11550 |
| 5.150 | 0.89 | 0.005 | 0.13 | 12566 |
| 5.641 | 1.84 | 0.01 | 0.23 | 11196 |
| 10.629 | 16763.02 | 99.94 | 1145.21 | 12034 |
| 13.531 | 5.95 | 0.04 | 0.30 | 9861 |
| Totals to | 16773.30 | 100 |
TABLE 4 liquid phase detection data for guanine (mother liquor with hydrochloric acid) obtained in example 2
| Retention time | Area of | Area percent | Peak height | Theoretical plate number |
| 3.199 | 0.68 | 0.00 | 0.14 | 13534 |
| 4.752 | 0.87 | 0.01 | 0.17 | 12051 |
| 4.909 | 1.36 | 0.01 | 0.19 | 7411 |
| 10.608 | 13848.14 | 99.95 | 979.45 | 12959 |
| 13.556 | 3.91 | 0.03 | 0.21 | 11348 |
| Totals to | 13854.96 | 100.00 |
Example 3
A high-efficiency environment-friendly guanine continuous synthesis process comprises the following steps:
(1) And (3) guanine crude product synthesis: 50 g of 2, 4-diamino-6-hydroxypyrimidine and 35 g of sodium nitrite are added into 450mL of water to prepare suspension; the peristaltic pump flow rate of the injected suspension is set to be 15mL/min, the peristaltic pump flow rate of the injected 35% hydrochloric acid 180mL is set to be 6mL/min, the two solutions are led into a pipeline (the inner diameter of the pipeline is 6mm and the length is 10 m) soaked in cold water at 10 ℃ for mixed reaction, and the reaction solution is injected into a reaction bottle and stirred continuously; after all the reaction liquid in the pipeline is injected into the reaction bottle, stirring is fully carried out for 30 minutes, the temperature is raised to 100 ℃ for evaporation and water removal until no water is distilled; 330 g of formamide and 10 g of sodium dithionite are added, the temperature is gradually increased to 160 ℃ to carry out formylation reaction, the temperature increasing time is controlled to be 4 hours, and the temperature is kept for 1 hour; continuously heating to 175 ℃ to carry out cyclization dehydration reaction, controlling the heating time to be 1 hour, preserving heat for 3 hours, and carrying out suction filtration to obtain guanine crude products and formamide mother liquor;
(2) Recovering formamide mother liquor: 172.1 g of formamide mother liquor is distilled under reduced pressure by a water pump at 120 ℃, and the temperature is continuously increased to 150 ℃ until no fraction is distilled out, and the front fraction is 14 g; the receiver was replaced again, formamide was distilled off under reduced pressure at 90℃with an oil pump, and the temperature was continuously raised to 130℃until no more fraction was distilled off, and 151 g of formamide was recovered.
(3) Guanine crude purification (fresh hydrochloric acid): 1000mL of hydrochloric acid with the concentration of 7% and the guanine crude product obtained in the step (1) are put into a reactor and heated to 90 ℃ to be fully dissolved into dark brown clear solution, 15 g of activated carbon is added, and the mixture is stirred and decolorized for 30 minutes; and filtering while the mixture is hot, cooling the filtrate to 15 ℃, and carrying out suction filtration to obtain guanine hydrochloride and hydrochloric acid mother liquor.
(4) Guanine crude product refining (hydrochloric acid mother liquor is used for application): adding the hydrochloric acid mother solution and another batch of guanine crude product obtained in the step (1) into a reactor, and heating to 90 ℃, wherein the guanine crude product is not fully dissolved into dark brown clear solution; adding 30mL of hydrochloric acid, fully dissolving to obtain dark brown clear solution, adding 15 g of active carbon, and stirring for decolorizing for 30 minutes; and then filtering while the mixture is hot, cooling the filtrate to 15 ℃, and carrying out suction filtration to obtain guanine hydrochloride (after hydrochloric acid mother liquor is applied) and hydrochloric acid mother liquor.
Adding 700mL of water into 2 batches of guanine hydrochlorides in the step (3) and the step (4), heating to 50 ℃, adjusting the pH to 7 by ammonia water, carrying out suction filtration to obtain a guanine finished product, drying and weighing 52.3 g of the former batch, and obtaining 99.96% of purity; the latter batch was 57.6 g with a purity of 99.96%.
(5) And (3) wastewater treatment and ammonium salt recovery: and collecting alkaline wastewater distilled in the reaction, combining the alkaline wastewater with alkaline wastewater of a flushing water diversion device, neutralizing hydrochloric acid mother liquor, supplementing ammonia water, adjusting the pH value to 7, filtering insoluble impurities, concentrating filtrate to obtain ammonium salt, and weighing 117.6 g after drying.
TABLE 5 liquid phase detection data for guanine (fresh hydrochloric acid) obtained in example 3
TABLE 6 liquid phase detection data for guanine (mother liquor with hydrochloric acid) obtained in example 3
| Retention time | Area of | Area percent | Peak height | Theoretical plate number |
| 3.199 | 0.75 | 0.00 | 0.16 | 14082 |
| 4.753 | 1.09 | 0.01 | 0.18 | 7540 |
| 5.639 | 0.85 | 0.00 | 0.11 | 11549 |
| 10.624 | 16211.86 | 99.96 | 1113.72 | 12166 |
| 13.530 | 4.28 | 0.03 | 0.21 | 9391 |
| Totals to | 16218.84 | 100.00 |
Example 4
A high-efficiency environment-friendly guanine continuous synthesis process comprises the following steps:
(1) And (3) guanine crude product synthesis: 50 g of 2, 4-diamino-6-hydroxypyrimidine and 30 g of sodium nitrite are added into 450mL of water to prepare suspension; the peristaltic pump flow rate of the injected suspension is set to be 15mL/min, the peristaltic pump flow rate of the injected 33% hydrochloric acid 180mL is set to be 6mL/min, the two solutions are led into a pipeline (the inner diameter of the pipeline is 6mm and the length is 10 m) soaked in cold water at 5 ℃ for mixed reaction, and the reaction solution is injected into a reaction bottle and stirred continuously; after all the reaction liquid in the pipeline is injected into the reaction bottle, stirring is fully carried out for 30 minutes, the temperature is raised to 100 ℃ for evaporation and water removal until no water is distilled; 360 g of formamide and 10 g of sodium dithionite are added, the temperature is gradually increased to 160 ℃ to carry out formylation reaction, the temperature increasing time is controlled to be 4 hours, and the temperature is kept for 1 hour; continuously heating to 175 ℃ to carry out cyclization dehydration reaction, controlling the heating time to be 1 hour, preserving heat for 3 hours, and carrying out suction filtration to obtain guanine crude products and formamide mother liquor;
(2) Recovering formamide mother liquor: 212.1 g of formamide mother liquor is distilled under reduced pressure by a water pump at 120 ℃, and the temperature is continuously increased to 150 ℃ until no fraction is distilled out, and the front fraction is 15 g; the receiver was replaced again, formamide was distilled off under reduced pressure at 90℃with an oil pump and the temperature was continuously raised to 130℃until no more fraction was distilled off, and 193 g of formamide was recovered.
(3) Guanine crude purification (fresh hydrochloric acid): adding 900mL of 8% hydrochloric acid and the guanine crude product obtained in the step (1) into a reactor, heating to 90 ℃ to fully dissolve the guanine crude product into dark brown clear solution, adding 13.5 g of active carbon, stirring and decoloring for 30 minutes; and filtering while the mixture is hot, cooling the filtrate to 20 ℃, and carrying out suction filtration to obtain guanine hydrochloride and hydrochloric acid mother liquor.
(4) Guanine crude product refining (hydrochloric acid mother liquor is used for application): adding the hydrochloric acid mother solution and another batch of guanine crude product obtained in the step (1) into a reactor, and heating to 90 ℃, wherein the guanine crude product is not fully dissolved into dark brown clear solution; adding 30mL of hydrochloric acid, fully dissolving to obtain dark brown clear solution, adding 13.5 g of active carbon, stirring and decoloring for 30 minutes; and then filtering while the mixture is hot, cooling the filtrate to 20 ℃, and carrying out suction filtration to obtain guanine hydrochloride (after hydrochloric acid mother liquor is applied) and hydrochloric acid mother liquor.
Adding 800mL of water into 2 batches of guanine hydrochlorides in the step (3) and the step (4), heating to 60 ℃, adjusting the pH to 7 by ammonia water, carrying out suction filtration to obtain a guanine finished product, drying and weighing 52.0 g of the former batch, and obtaining the guanine finished product with the purity of 99.93%; the latter batch was 57.2 g with a purity of 99.90%.
(5) And (3) wastewater treatment and ammonium salt recovery: and collecting alkaline wastewater distilled in the reaction, combining the alkaline wastewater with alkaline wastewater of a flushing water diversion device, neutralizing hydrochloric acid mother liquor, supplementing ammonia water, adjusting the pH value to 7, filtering insoluble impurities, concentrating filtrate to obtain ammonium salt, and weighing 123.6 g after drying.
TABLE 7 liquid phase detection data for guanine (fresh hydrochloric acid) obtained in example 4
| Retention time | Area of | Area percent | Peak height | Theoretical plate number |
| 3.196 | 0.79 | 0.00 | 0.17 | 13598 |
| 4.754 | 1.19 | 0.01 | 0.19 | 9350 |
| 4.987 | 1.04 | 0.00 | 0.11 | 5542 |
| 5.633 | 2.72 | 0.02 | 0.34 | 11387 |
| 10.615 | 17816.96 | 99.93 | 1201.21 | 11651 |
| 13.504 | 6.74 | 0.04 | 0.34 | 10033 |
| Totals to | 17829.45 | 100 |
TABLE 8 liquid phase detection data for guanine (mother liquor with hydrochloric acid) obtained in example 4
| Retention time | Area of | Area percent | Peak height | Theoretical plate number |
| 3.194 | 0.89 | 0.00 | 0.20 | 15082 |
| 4.754 | 1.40 | 0.01 | 0.21 | 10675 |
| 5.640 | 1.30 | 0.01 | 0.17 | 11649 |
| 10.645 | 19048.98 | 99.90 | 1262.39 | 11277 |
| 13.539 | 8.78 | 0.05 | 0.50 | 13442 |
| 25.105 | 6.04 | 0.03 | 0.22 | 18128 |
| Totals to | 19067.39 | 100 |
Example 5
A high-efficiency environment-friendly guanine continuous synthesis process comprises the following steps:
(1) And (3) guanine crude product synthesis: 50 g of 2, 4-diamino-6-hydroxypyrimidine and 30 g of sodium nitrite are added into 450mL of water to prepare suspension; the peristaltic pump flow rate of the injected suspension is set to be 15mL/min, the peristaltic pump flow rate of the injected 33% hydrochloric acid 180mL is set to be 6mL/min, the two solutions are led into a pipeline (the inner diameter of the pipeline is 6mm and the length is 10 m) soaked in cold water at 5 ℃ for mixed reaction, and the reaction solution is injected into a reaction bottle and stirred continuously; after all the reaction liquid in the pipeline is injected into the reaction bottle, stirring is fully carried out for 30 minutes, the temperature is raised to 100 ℃ for evaporation and water removal until no water is distilled; 360 g of formamide and 10 g of sodium dithionite are added, the temperature is gradually increased to 160 ℃ to carry out formylation reaction, the temperature increasing time is controlled to be 4 hours, and the temperature is kept for 1 hour; continuously heating to 175 ℃ to carry out cyclization reflux reaction, controlling the heating time to be 1 hour, preserving the heat for 3 hours, and carrying out suction filtration to obtain guanine crude products and formamide mother liquor;
(2) Recovering formamide mother liquor: distilling 210.1 g of formamide mother liquor under reduced pressure by using a water pump at 120 ℃, and continuously heating to 150 ℃ until no fraction is distilled out, wherein the front fraction is 16 g; the receiver was replaced again, formamide was distilled off under reduced pressure using an oil pump at 90℃and the temperature was increased continuously to 130℃until no more fraction was distilled off, and 189 g of formamide was recovered.
(3) Guanine crude purification (fresh hydrochloric acid): adding 900mL of 8% hydrochloric acid and the guanine crude product obtained in the step (1) into a reactor, heating to 90 ℃ to fully dissolve the guanine crude product into dark brown clear solution, adding 13.5 g of active carbon, stirring and decoloring for 30 minutes; and filtering while the mixture is hot, cooling the filtrate to 20 ℃, and carrying out suction filtration to obtain guanine hydrochloride and hydrochloric acid mother liquor.
(4) Guanine crude product refining (hydrochloric acid mother liquor is used for application): adding the hydrochloric acid mother solution and another batch of guanine crude product obtained in the step (1) into a reactor, and heating to 90 ℃, wherein the guanine crude product is not fully dissolved into dark brown clear solution; adding 30mL of hydrochloric acid, fully dissolving to obtain dark brown clear solution, adding 13.5 g of active carbon, stirring and decoloring for 30 minutes; and then filtering while the mixture is hot, cooling the filtrate to 20 ℃, and carrying out suction filtration to obtain guanine hydrochloride (after hydrochloric acid mother liquor is applied) and hydrochloric acid mother liquor.
Adding 800mL of water into 2 batches of guanine hydrochlorides in the step (3) and the step (4), heating to 60 ℃, adjusting the pH to 7 by ammonia water, carrying out suction filtration to obtain a guanine finished product, drying and weighing 51.3 g of the former batch, and obtaining 99.69% of the purity; the latter batch was 55.8 g, 99.72% pure.
(5) And (3) wastewater treatment and ammonium salt recovery: and collecting alkaline wastewater distilled in the reaction, combining the alkaline wastewater with alkaline wastewater of a flushing water diversion device, neutralizing hydrochloric acid mother liquor, supplementing ammonia water, adjusting the pH value to 7, filtering insoluble impurities, concentrating filtrate to obtain ammonium salt, and weighing 126.6 g after drying.
TABLE 9 liquid phase detection data for guanine (fresh hydrochloric acid) obtained in example 5
| Retention time | Area of | Area percent | Peak height | Theoretical plate number |
| 3.197 | 0.70 | 0.01 | 0.14 | 13905 |
| 5.174 | 0.39 | 0.01 | 0.06 | 14476 |
| 5.786 | 1.16 | 0.02 | 0.14 | 11782 |
| 9.334 | 11.27 | 0.15 | 0.91 | 13628 |
| 10.629 | 7319.13 | 99.69 | 562.04 | 15828 |
| 13.709 | 9.04 | 0.12 | 0.59 | 18510 |
| Totals to | 7341.69 | 100 |
TABLE 10 liquid phase detection data for guanine (mother liquor with hydrochloric acid) obtained in example 5
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Example 5 is a comparative experiment to example 4, except that after the low temperature formylation reaction, the water produced by the cyclization was allowed to continuously reflux during the high Wen Huange reaction in example 5. As can be seen from the results of example 5, if the high temperature cyclization dehydration step is such that water generated by the cyclization is not distilled off, both the front and rear impurity peaks of the main peak guanine are significantly increased. Namely, the present invention can further improve the purity of guanine by employing a cyclization dehydration reaction instead of a cyclization reflux reaction.
In summary, by adopting the process of the invention, each batch of guanine finished products is an off-white solid, the purity of the guanine finished products is more than 99.6%, and the total yield of the guanine finished products obtained by the reaction is more than 89% (calculated by half before and after the application). The invention can also reduce the waste water and energy consumption generated by the process, and reduce the production cost and the environmental protection cost of the whole process flow.
The above-described embodiments of the present invention do not limit the scope of the present invention. Any of various other corresponding changes and modifications made according to the technical idea of the present invention should be included in the scope of the claims of the present invention.
Claims (10)
1. The efficient environment-friendly continuous guanine synthesis process is characterized by comprising the following steps of:
s100, synthesizing a guanine crude product; optionally, the composition may be in the form of a gel,
s200, recovering formamide mother liquor;
s300, refining a guanine crude product;
wherein, the steps of the guanine crude product synthesis include:
s101, uniformly mixing 2, 4-diamino-6-hydroxypyrimidine, sodium nitrite and first water to obtain a suspension;
s102, introducing the suspension and the first hydrochloric acid solution into a pipeline for mixed reaction, and injecting the reaction solution into a reaction bottle for continuous stirring;
s103, after all the reaction liquid in the pipeline is injected into the reaction bottle, continuing stirring to uniformly mix the reaction liquid, and then evaporating to remove water until no water is distilled;
s104, adding formamide and a catalyst into the reaction bottle, sequentially carrying out formylation reaction at 100-160 ℃ and cyclization reaction at 160-175 ℃, and carrying out suction filtration to obtain guanine crude product and formamide mother liquor.
2. The efficient and environment-friendly continuous guanine synthesis process according to claim 1, wherein in step S101, the mass ratio of the 2, 4-diamino-6-hydroxypyrimidine to sodium nitrite to the first water is 1: (0.5-0.7): (7.5-11); in the step S102, the mass fraction of the first hydrochloric acid solution is 30% -35%, and the dosage ratio of the 2, 4-diamino-6-hydroxypyrimidine to the first hydrochloric acid solution is 1g: (3-5) mL; in step S104, the catalyst is at least one of sodium sulfide, sodium thiosulfate or sodium dithionite; the mass ratio of the 2, 4-diamino-6-hydroxypyrimidine to the formamide to the catalyst is 1: (5-7): (0.1-0.2).
3. The efficient environment-friendly guanine continuous synthesis process according to claim 1, wherein in step S102, the inner diameter of the pipeline is 2-20 mm, and the length of the pipeline is 5-20 m; the flow rate of the suspension into the pipeline is 15-20 mL/min, and the flow rate of the first hydrochloric acid solution into the pipeline is 5-10 mL/min.
4. The efficient and environment-friendly continuous guanine synthesis process according to claim 1, wherein in step S102, the suspension and the first hydrochloric acid solution are mixed in a pipeline, and the pipeline is immersed in cold water at 0-20 ℃.
5. The efficient and environment-friendly continuous guanine synthesis process according to claim 1, wherein in step S104, the temperature is raised from 100 ℃ to 160 ℃ at a temperature raising rate of 0.1-0.3 ℃/min, and the total time of the whole temperature raising stage and the whole heat preserving stage is 4-6 h; in the process of the cyclization reaction, the temperature is increased from 160 ℃ to 175 ℃ at the heating rate of 0.1-0.5 ℃/min, and the total time of the whole heating stage and the heat preservation stage is 3-5 h.
6. The efficient and environment-friendly guanine continuous synthesis process according to claim 1, wherein the cyclization reaction is a cyclization reflux reaction or a cyclization dehydration reaction.
7. The efficient and environmentally friendly continuous guanine synthesis process according to claim 1, wherein said step of recovering the mother liquor of formamide comprises:
s201, performing first reduced pressure distillation on the formamide mother liquor obtained after suction filtration in the step S104 through a water pump to obtain a front fraction;
s202, performing second reduced pressure distillation on the formamide mother liquor subjected to the first reduced pressure distillation through an oil pump, and recovering formamide; wherein,
in the first reduced pressure distillation process, firstly heating to 110-130 ℃ to start reduced pressure distillation, and continuously heating to 140-160 ℃ until no fraction is distilled out; the temperature of the cooling liquid introduced into the condensing tube jacket is 10-20 ℃;
in the second reduced pressure distillation process, firstly heating to 80-100 ℃ to start reduced pressure distillation, and continuously heating to 120-140 ℃ until no fraction is distilled out; the temperature of the cooling liquid introduced into the condensing tube jacket is 5-10 ℃.
8. The efficient and environment-friendly continuous guanine synthesis process according to claim 1, wherein the step of refining the crude guanine product comprises the steps of:
s301, adding the guanine crude product into a second hydrochloric acid solution, and fully dissolving the guanine crude product into a dark brown clear solution;
s302, adding active carbon into dark brown clear liquid, stirring and decoloring, and then filtering while the mixture is hot, cooling and suction-filtering filtrate to obtain guanine hydrochloride and hydrochloric acid mother liquor;
s303, dissolving guanine hydrochloride into second water, then regulating the pH value to 6-8 by ammonia water, and obtaining a guanine finished product through suction filtration; wherein,
the mass fraction of the second hydrochloric acid solution is 7% -10%; the dosage ratio of the guanine crude product to the second hydrochloric acid solution is 1g: (10-20) mL;
in the process of fully dissolving the guanine crude product into dark brown clear solution, heating to 80-90 ℃;
the dosage ratio of the activated carbon to the dark brown clarified liquid is (0.01-0.03) g:1mL;
the temperature of stirring and decoloring is not more than 90 ℃;
the temperature of the filtrate after cooling is 10-20 ℃;
the hydrochloric acid mother liquor is used for refining guanine crude products in other batches;
the mass ratio of the guanine hydrochloride to the second water is 1: (5-20);
in the process of dissolving guanine hydrochloride in the second water, the guanine hydrochloride needs to be heated to 50-60 ℃.
9. The efficient and environmentally friendly continuous guanine synthesis process according to claim 8, further comprising S400, wastewater treatment recovery of ammonium salt: the hydrochloric acid mother liquor in the step S302 is neutralized by the alkaline waste water distilled in the step S104 and/or the alkaline waste water generated by the flushing water diversion device, the pH is adjusted to 6-8, and then the ammonium salt is obtained through filtration, concentration, cooling and crystallization; wherein,
in the process of neutralizing hydrochloric acid mother liquor by the alkaline wastewater distilled out in the step S104 and/or the alkaline wastewater generated by the flushing water diversion device, when the alkaline wastewater is insufficient, adding ammonia water;
the hydrochloric acid mother solution is the hydrochloric acid mother solution with the concentration of more than 20% in the step S302, which can not be continuously used.
10. The efficient environment-friendly guanine continuous synthesis device is characterized by comprising a pipeline and a reaction bottle which are sequentially communicated;
the efficient and environment-friendly guanine continuous synthesis apparatus is used for executing the efficient and environment-friendly guanine continuous synthesis process according to any one of claims 1 to 9.
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