CN114702522A - Preparation method and reaction device of diethoxyethylphosphane - Google Patents
Preparation method and reaction device of diethoxyethylphosphane Download PDFInfo
- Publication number
- CN114702522A CN114702522A CN202210379143.2A CN202210379143A CN114702522A CN 114702522 A CN114702522 A CN 114702522A CN 202210379143 A CN202210379143 A CN 202210379143A CN 114702522 A CN114702522 A CN 114702522A
- Authority
- CN
- China
- Prior art keywords
- reaction tube
- reaction
- sealing
- diethoxyethylphosphane
- reactants
- 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.)
- Pending
Links
- 238000006243 chemical reaction Methods 0.000 title claims abstract description 152
- 238000002360 preparation method Methods 0.000 title claims abstract description 26
- XKEABTCTAJJFOP-UHFFFAOYSA-N 2,2-diethoxyethylphosphane Chemical compound CCOC(CP)OCC XKEABTCTAJJFOP-UHFFFAOYSA-N 0.000 title abstract description 30
- 238000007789 sealing Methods 0.000 claims abstract description 54
- 239000000376 reactant Substances 0.000 claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 20
- 238000002844 melting Methods 0.000 claims abstract description 7
- 230000008018 melting Effects 0.000 claims abstract description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 54
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 32
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- FWFZRPMNAAFGBA-UHFFFAOYSA-N 2-phosphanylethylphosphane Chemical compound PCCP FWFZRPMNAAFGBA-UHFFFAOYSA-N 0.000 claims description 25
- 239000011521 glass Substances 0.000 claims description 18
- 239000007789 gas Substances 0.000 claims description 12
- FJKIXWOMBXYWOQ-UHFFFAOYSA-N ethenoxyethane Chemical compound CCOC=C FJKIXWOMBXYWOQ-UHFFFAOYSA-N 0.000 claims description 10
- 230000001681 protective effect Effects 0.000 claims description 8
- BYTNQSLSCFWBSI-UHFFFAOYSA-N 2-ethoxyethylphosphane Chemical compound CCOCCP BYTNQSLSCFWBSI-UHFFFAOYSA-N 0.000 claims description 7
- 239000011261 inert gas Substances 0.000 claims description 2
- 239000011541 reaction mixture Substances 0.000 claims 1
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 abstract description 17
- 230000000694 effects Effects 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract 1
- 238000004821 distillation Methods 0.000 description 13
- 238000001816 cooling Methods 0.000 description 11
- 239000000155 melt Substances 0.000 description 10
- 239000011259 mixed solution Substances 0.000 description 10
- 238000010438 heat treatment Methods 0.000 description 8
- 229920006395 saturated elastomer Polymers 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- 238000011049 filling Methods 0.000 description 7
- -1 2-ethoxyethyl Chemical group 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 3
- 239000004810 polytetrafluoroethylene Substances 0.000 description 3
- 229960004113 tetrofosmin Drugs 0.000 description 3
- ZSSWXNPRLJLCDU-UHFFFAOYSA-N 1-diethylphosphorylethane Chemical compound CCP(=O)(CC)CC ZSSWXNPRLJLCDU-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- CYMAFSFDGZKOCN-UHFFFAOYSA-N bis(2-ethoxyethyl)phosphane Chemical compound CCOCCPCCOCC CYMAFSFDGZKOCN-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 238000002485 combustion reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- 230000002269 spontaneous effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229910052713 technetium Inorganic materials 0.000 description 2
- GKLVYJBZJHMRIY-UHFFFAOYSA-N technetium atom Chemical compound [Tc] GKLVYJBZJHMRIY-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- APQIUTYORBAGEZ-UHFFFAOYSA-N 1,1-dibromoethane Chemical compound CC(Br)Br APQIUTYORBAGEZ-UHFFFAOYSA-N 0.000 description 1
- DQTGWWXQOJWLME-UHFFFAOYSA-N 2-diethoxyphosphoryloxyethyl diethyl phosphate Chemical compound CCOP(=O)(OCC)OCCOP(=O)(OCC)OCC DQTGWWXQOJWLME-UHFFFAOYSA-N 0.000 description 1
- HZTUQWZPFRZDSH-UHFFFAOYSA-N CCOCCC1(CCOCC)CCPCC1 Chemical compound CCOCCC1(CCOCC)CCPCC1 HZTUQWZPFRZDSH-UHFFFAOYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- VZZJVOCVAZHETD-UHFFFAOYSA-N diethylphosphane Chemical compound CCPCC VZZJVOCVAZHETD-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- QCWJONLQSHEGEJ-UHFFFAOYSA-N tetrofosmin Chemical compound CCOCCP(CCOCC)CCP(CCOCC)CCOCC QCWJONLQSHEGEJ-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4025—Esters of poly(thio)phosphonic acids
- C07F9/4028—Esters of poly(thio)phosphonic acids containing no further substituents than -PO3H2 groups in free or esterified form
- C07F9/4031—Acyclic unsaturated derivatives
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
Abstract
The invention provides a preparation method and a reaction device of diethoxyethylphosphane. The preparation process of diethoxyethylphosphane includes setting reactant inside the reaction tube, sealing the end of the reaction tube and oil bath reaction. The reaction device is a reaction tube used in the preparation method of the diethoxyethylphosphane, and the reaction tube comprises a containing part suitable for placing reactants and a sealing part suitable for sealing by fusing. The invention realizes the sealing of the reaction tube by sealing through melting instead of sealing the reaction tube through the rotary cover, greatly improves the sealing effect of the reaction tube, can prevent vinyl ether in the reaction tube from volatilizing and leaking in the oil bath process, and ensures that the vinyl ether can fully react, thereby being beneficial to improving the yield and the purity of the prepared diethoxyethylphosphane.
Description
Technical Field
The invention relates to the technical field of chemical preparation, in particular to a preparation method and a reaction device of diethoxyethylphosphine.
Background
The stannous tetrofosmin for injection is a technetium labeled medicine box, which is labeled by radioactive isotope technetium99mTc-tetrofosmin (99mTc-bis (ethoxyethylphosphine) injection is a radioactive diagnostic drug and is clinically used for myocardial perfusion imaging.9mThe radiochemical purity of the Tc-tetrofosmin injection isThe key influencing the clinical imaging quality is that the ligand compound is bis (ethoxyethylphosphine) with the chemical name of 1, 2-bis (2-ethoxyethyl) phosphine]Ethane) is critical to affect its radiochemical purity.
The synthesis of diethoxyethylphosphane is generally carried out by the following general method: reacting diethyldiphosphine (H)2PC2H4PH2Chemical name 1, 2-bis (phosphino) ethane) and vinyl ethyl ether, then adding azobisisobutyronitrile, uniformly mixing, filling nitrogen, sealing, then placing in an oil bath at 75 ℃ for reaction for 16 hours, and then cooling to room temperature. And (3) after cooling, carrying out reduced pressure distillation on the reactants at the temperature of 80 ℃ for 1h, removing unreacted vinyl ethyl ether and ethanediphosphine in the process, decomposing azodiisobutyronitrile into low molecular substances, and continuously evaporating the low molecular substances to obtain the diethoxyethylphosphane.
The above reaction is generally carried out in a common glass tube, and a polytetrafluoroethylene screw cap is screwed on the glass tube for sealing, so that the yield of the obtained diethoxyethylphosphane is 70%, and the purity is 98%. At present, the diethoxyethylphosphane is not purified by a method after the preparation of the diethoxyethylphosphane is finished, so that the control of the preparation of the diethoxyethylphosphane and the control of the reaction process are important, but tests show that the yield and the purity cannot be effectively improved by only adjusting parameters, and the prior art does not disclose any record for effectively controlling the reaction process and further obviously improving the yield and the purity of the diethoxyethylphosphane.
Disclosure of Invention
The invention aims to solve the technical problem of overcoming the defect that the yield and the purity of the diethoxyethylphosphane are difficult to improve in the prior art.
The invention provides a preparation method of diethoxyethylphosphane, which comprises the steps of placing reactants into a reaction tube, sealing the end part of the reaction tube by melting, and carrying out oil bath reaction.
Optionally, after all reactants are added, protective gas is filled into the reaction tube immediately, and then the reaction tube is sealed by melting.
Optionally, the shielding gas is nitrogen or inert gas.
Optionally, the reaction was added under ice bath conditions.
Optionally, the reaction tube is removed from the ice bath during sealing.
Optionally, the reactants include ethylene diphosphine, vinyl ethyl ether, and azobisisobutyronitrile.
Optionally, when the reactants are added, the azobisisobutyronitrile is added into the reaction tube, and then the protective gas is introduced into the reaction tube to add the other reactants.
Optionally, when the reactants are added, the ethylene diphosphine is pressed into the reaction tube by a protective gas.
The invention also provides a reaction device, which is a reaction tube used in the preparation method of the bis-ethoxyethylphosphinane, and the reaction tube comprises a containing part suitable for placing reactants and a sealing part suitable for sealing by melting.
Optionally, the length of the sealing part is greater than the length of the accommodating part.
Optionally, the reaction tube is an integrally formed glass tube.
The technical scheme of the invention has the following advantages:
1. according to the preparation method of the bis (ethoxyethylphosphine) provided by the invention, the inventor researches and discovers that in the step of oil bath chemical reaction at the temperature of 75 ℃, the vinyl ether is easy to leak during the reaction at the temperature of 75 ℃ because the boiling point (35.6 ℃) of the vinyl ether is low, and in the process of the oil bath chemical reaction, the problems of large reaction pressure, long reaction time and poor sealing effect exist, so that the leakage of the vinyl ether is difficult to inhibit, the proportion of reactants is unbalanced, so that the ethylene diphosphine is not completely reacted to form a polymer, and is difficult to remove finally, and the yield and the purity of the product are reduced. Based on the discovery of the problems, the invention adopts a means of carrying out oil bath reaction after the reactants are sealed in the reaction tube by melting, the reaction tube is sealed by melting instead of screwing the cover, the sealing effect of the reaction tube is greatly improved, the vinyl ether in the reaction tube can be prevented from volatilizing and leaking in the oil bath process, the reaction can be fully carried out, and the yield and the purity of the prepared diethoxyethylphosphane are effectively improved.
2. According to the preparation method of the bis-ethoxyethylphosphine, provided by the invention, the ethylene diphosphine in reactants is extremely active in chemical property, and is easily oxidized at normal temperature and easily spontaneously combusted in air, so that the ethylene diphosphine is generally required to be collected into a liquid collecting bottle filled with protective gas, but in the process of adding the ethylene diphosphine into a reaction tube, the ethylene diphosphine is easily exposed in air to cause spontaneous combustion or oxidation, the protective gas is filled into the reaction tube before and after the addition of the ethylene diphosphine, and the ethylene diphosphine is pressed into the reaction tube through the protective gas, so that the contact between the ethylene diphosphine and the air can be fully isolated, the oxidation loss of the ethylene diphosphine is reduced, and the influence of the active chemical property of the ethylene diphosphine on the yield and the purity of a product is reduced.
3. According to the preparation method of the bis-ethoxyethylphosphine, the ethylene diphosphine in the reactant is easily oxidized at normal temperature, the proportion of the reactant is unbalanced, the yield and the purity of the product are influenced, and the temperature of the reactant can be reduced by adding the reactant under the ice bath condition, so that the oxidation rate of the ethylene diphosphine is reduced, and the yield and the purity of the reactant are improved.
4. According to the preparation method of the diethoxyethylphosphane, provided by the invention, after the reactants are added, the reaction tube is taken out from the ice bath condition and then is subjected to melt sealing, so that the temperature of the reactants is increased in the melt sealing process, the low boiling point and the protective gas are volatilized towards the tube opening of the reaction tube, the phenomenon that air is poured into the reaction tube reversely to cause the oxidation of the diethyldiphosphine is prevented, the full reaction of the diethyldiphosphine is facilitated, and the yield and the purity of the product are ensured.
5. According to the preparation method of the diethoxyethylphosphane, provided by the invention, in the existing preparation method of the diethoxyethylphosphane, oxidation and spontaneous combustion of the diethyldiphosphine are avoided through reaction in a glove box, so that the yield and purity of the product are improved, the yield and purity of the product can be ensured without adding reaction materials in the glove box, the production environment of the diethoxyethylphosphane is not harsh, and the cost for preparing the diethoxyethylphosphane is reduced.
6. According to the reaction device provided by the invention, the length of the accommodating part is greater than that of the reaction tube, so that heat during sealing is minimized to influence reactants, volatilization of vinyl ether is reduced, and the reactants are ensured to fully react.
7. According to the reaction device provided by the invention, the reaction tubes are integrally formed glass tubes, are completely made of the same material, cannot generate gaps caused by different expansion coefficients in an oil bath process due to different materials, and are high in sealing performance after being fused and sealed.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 is a schematic view of a reaction apparatus provided in example 1 of the present invention;
FIG. 2 is a schematic view of the connection between the collection flask and the reaction tube according to the embodiment of the present invention.
Reference numerals: 1. an accommodating portion; 2. and (7) sealing the part by fusing.
Detailed Description
The following examples are provided to further understand the present invention, not to limit the scope of the present invention, but to provide the best mode, not to limit the content and the protection scope of the present invention, and any product similar or similar to the present invention, which is obtained by combining the present invention with other prior art features, falls within the protection scope of the present invention.
The examples do not show the specific experimental steps or conditions, and can be performed according to the conventional experimental steps described in the literature in the field. The reagents or instruments used are not indicated by manufacturers, and are all conventional reagent products which can be obtained commercially.
Vinyl ethyl ether (99%, reagent grade) in the examples of the invention was purchased from Acros;
triethyl phosphine oxide (98%, reagent grade) in the examples of the invention was purchased from alatin;
in the embodiment of the invention, azobisisobutyronitrile (98%, reagent grade) is purchased from Beijing YinuoKai science and technology Co., Ltd;
ethylenediphosphine (H) in the examples of the invention2PC2H4PH2Chemical name 1, 2-bis (phosphino) ethane) is self-made, and ethylene diphosphine needs to be prepared in advance in each example and comparative example, and the preparation method comprises the following steps:
synthesis of (C)2H5O)2P(O)C2H4(O)P(OC2H5)2(tetraethyl ethylene diphosphate): 314g of triethyl phosphine oxide and 200 g of dibromoethane are taken and placed in a 500mL flask, a high-efficiency fractionating column is added, oil bath is carried out at the temperature of 145 ℃ and 150 ℃ for 1.5h, the fraction components are removed, then the residual reactant in the flask is cooled to the room temperature, and then reduced pressure distillation is carried out, thus obtaining (C) of 155 ℃ and 157 ℃/1mmHg2H5O)2P(O)C2H4(O)P(OC2H5)2 62g；
Obtaining ethanediphosphine: dry nitrogen is introduced into a reaction flask, 20g of lithium aluminum hydride and 500mL of anhydrous ether are added into the reaction flask, and then 50g of (C) is slowly added dropwise2H5O)2P(O)C2H4(O)P(OC2H5)2And 60mL of anhydrous ether, and maintaining the temperature of the reaction system at-2-0 ℃; after the dropwise addition, standing at room temperature overnight, then slowly dropwise adding 400mL of 6N concentrated hydrochloric acid while stirring to obtain a reactant, transferring the reactant into a clean flask, adding 10g of anhydrous sodium sulfate, drying at normal temperature for 8h, transferring the dried reactant into a 500mL flask, and distilling under normal pressure under the protection of nitrogen to obtain 3g of ethylene diphosphine, wherein the distillation temperature is 114-.
Example 1
This example provides a reaction apparatus, which is a reaction tube as shown in FIG. 1, and the reaction tube is an integrally molded glass tube. The reaction tube comprises a containing part 1 suitable for placing reactants and a sealing part 2 suitable for sealing by fusing, wherein the length of the sealing part 2 is greater than that of the containing part 1, and the length of the sealing part 2 is 4 times that of the containing part 1.
The embodiment provides a preparation method of diethoxyethylphosphane, which comprises the following steps:
putting 15mL of vinyl ether into a collecting bottle, filling nitrogen into the collecting bottle and sealing, and when preparing the ethanediphosphine, directly inoculating 3g of the distilled ethanediphosphine into the collecting bottle to obtain a mixed solution;
taking the reaction tube, immersing the bottom of the reaction tube into an ice-water bath, putting 0.3g of azobisisobutyronitrile into the reaction tube, introducing nitrogen into the reaction tube until the reaction tube is saturated, referring to fig. 2, connecting a collection bottle in which vinyl ether and ethylene diphosphine are collected with the reaction tube through a hose, immersing the end part of the hose into the azobisisobutyronitrile, introducing nitrogen into the collection bottle to press the mixed solution in the collection bottle into the reaction tube, and immediately introducing nitrogen into the reaction tube again until the reaction tube is saturated with nitrogen;
taking out the reaction tube under the ice bath condition, inclining the reaction tube, heating the upper end close to the melt sealing part by using an alcohol blast burner, continuously rotating the reaction tube during heating, and slightly pulling the upper end of the melt sealing part when the reaction tube is softened so as to separate the upper end of the melt sealing part from the reaction tube to finish melt sealing;
and (3) standing and cooling the reaction tube after melt sealing, then placing the reaction tube in a 75 ℃ oil bath for reaction for 16h, cooling to room temperature after reaction, transferring the solution in the reaction tube into a 50mL distillation flask, and carrying out reduced pressure distillation at 80 ℃ for 1h to obtain the diethoxyethylphosphane.
Example 2
This example provides a process for preparing diethoxyethylphosphane, the only difference between the reactor used in the preparation and the reactor used in example 1 is: the length of the fusion-sealed part 2 is 3 times of the length of the accommodating part 1, and the preparation method comprises the following steps:
putting 15mL of vinyl ether into a collecting bottle, filling nitrogen into the collecting bottle and sealing, and when preparing the ethanediphosphine, directly inoculating 3g of the distilled ethanediphosphine into the collecting bottle to obtain a mixed solution;
taking a reaction tube, immersing the bottom of the reaction tube into an ice-water bath, putting 0.3g of azobisisobutyronitrile into the reaction tube, introducing nitrogen into the reaction tube until the reaction tube is saturated, referring to fig. 2, connecting a collection bottle in which vinyl ether and ethylene diphosphine are collected with the reaction tube through a hose, immersing the end part of the hose into the azobisisobutyronitrile, introducing nitrogen into the collection bottle, and pressing the mixed solution in the collection bottle into the reaction tube;
taking out the reaction tube under the ice bath condition, inclining the reaction tube, heating the upper end close to the melt sealing part by using an alcohol blast burner, continuously rotating the reaction tube during heating, and slightly pulling the upper end of the melt sealing part when the reaction tube is softened so as to separate the upper end of the melt sealing part from the reaction tube to finish melt sealing;
and (3) standing and cooling the reaction tube after melt sealing, then placing the reaction tube in a 75 ℃ oil bath for reaction for 16h, cooling to room temperature after reaction, transferring the solution in the reaction tube into a 50mL distillation flask, and carrying out reduced pressure distillation at 80 ℃ for 1h to obtain the diethoxyethylphosphane.
Example 3
This example provides a method for preparing bis (ethoxyethylphosphine), wherein the reaction apparatus used in the preparation process is the same as that in example 1, and the preparation method comprises the following steps:
putting 15mL of vinyl ether into a collecting bottle, filling nitrogen into the collecting bottle, sealing, and directly introducing 3g of distilled diethyl ether into the collecting bottle to obtain a mixed solution when preparing diethyl phosphine;
taking a reaction tube, immersing the bottom of the reaction tube into an ice-water bath, putting 0.3g of azobisisobutyronitrile into the reaction tube, referring to fig. 2, connecting a collection bottle in which vinyl ether and ethylene diphosphine are collected with the reaction tube through a hose, immersing the end part of the hose into the azobisisobutyronitrile, introducing nitrogen into the collection bottle to press the mixed solution in the collection bottle into the reaction tube, and immediately filling nitrogen into the reaction tube again until the nitrogen is saturated;
taking out the reaction tube under the ice bath condition, inclining the reaction tube, heating the upper end close to the melt sealing part by using an alcohol blast burner, continuously rotating the reaction tube during heating, and slightly pulling the upper end of the melt sealing part when the reaction tube is softened so as to separate the upper end of the melt sealing part from the reaction tube to finish melt sealing;
and (3) standing and cooling the reaction tube after melt sealing, then placing the reaction tube in a 75 ℃ oil bath for reaction for 16h, cooling to room temperature after reaction, transferring the solution in the reaction tube into a 50mL distillation flask, and carrying out reduced pressure distillation at 80 ℃ for 1h to obtain the diethoxyethylphosphane.
Example 4
This example provides a method for preparing bis (ethoxyethylphosphine), wherein the reaction apparatus used in the preparation is the same as the reaction apparatus in example 1, and the method comprises the following steps:
putting 15mL of vinyl ether into a collecting bottle, filling nitrogen into the collecting bottle and sealing, and when preparing the ethanediphosphine, directly inoculating 3g of the distilled ethanediphosphine into the collecting bottle to obtain a mixed solution;
taking a reaction tube, putting 0.3g of azobisisobutyronitrile into the reaction tube, introducing nitrogen into the reaction tube until the reaction tube is saturated, referring to fig. 2, connecting a collection bottle in which vinyl ether and ethylene diphosphine are collected with the reaction tube through a hose, immersing the end part of the hose into the azobisisobutyronitrile, introducing nitrogen into the collection bottle to press the mixed solution in the collection bottle into the reaction tube, and immediately introducing nitrogen into the reaction tube again until the reaction tube is saturated with nitrogen;
inclining the reaction tube, heating the upper end close to the melt-sealing part by using an alcohol blast burner, continuously rotating the reaction tube during heating, and slightly pulling the upper end of the melt-sealing part when the reaction tube is softened to separate the upper end of the melt-sealing part from the reaction tube to finish melt-sealing;
and (3) standing and cooling the reaction tube after melt sealing, then placing the reaction tube in a 75 ℃ oil bath for reaction for 16h, cooling to room temperature after reaction, transferring the solution in the reaction tube into a 50mL distillation flask, and carrying out reduced pressure distillation at 80 ℃ for 1h to obtain the diethoxyethylphosphane.
Comparative example 1
The comparative example provides a preparation method of diethoxyethylphosphane, which comprises the following steps:
putting 15mL of vinyl ether into a collecting bottle, filling nitrogen into the collecting bottle and sealing, and when preparing the ethanediphosphine, directly inoculating 3g of the distilled ethanediphosphine into the collecting bottle to obtain a mixed solution;
taking a glass tube with a polytetrafluoroethylene screw cap, immersing the bottom of the glass tube into an ice-water bath, taking 0.3g of azodiisobutyronitrile, putting the azodiisobutyronitrile into the glass tube, introducing nitrogen into the glass tube until the glass tube is saturated, connecting a collecting bottle which is collected with vinyl ether and ethylene diphosphine with the glass tube through a hose by using the method in example 1, immersing the end part of the hose into the azodiisobutyronitrile, introducing nitrogen into the collecting bottle to press the mixed solution in the collecting bottle into the glass tube, immediately introducing nitrogen into the glass tube again until the glass tube is saturated with nitrogen, and screwing the screw cap made of polytetrafluoroethylene on the glass tube for sealing;
and then placing the glass tube in a 75 ℃ oil bath for reaction for 16h, cooling to room temperature after the reaction, transferring the solution in the glass tube into a 50mL distillation flask, and carrying out reduced pressure distillation at 80 ℃ for 1h to obtain the diethoxyethylphosphane.
Test examples
The purity of the bis (ethoxyethylphosphinane) obtained in examples and comparative examples was measured by high performance liquid chromatography, and the yield and purity were calculated in terms of the reaction molar ratio and are shown in Table 1.
TABLE 1 product yield and purity of examples and comparative examples
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. This need not be, nor should it be exhaustive of all embodiments. And obvious variations or modifications derived therefrom are intended to be within the scope of the invention.
Claims (10)
1. A preparation method of bis (ethoxyethylphosphine) is characterized in that reactants are put into a reaction tube, and then an oil bath reaction is carried out after the end part of the reaction tube is sealed.
2. The process according to claim 1, wherein the reaction tube is immediately filled with a shielding gas after all the reactants are completely added, and then the reaction tube is sealed by melting.
3. The method according to claim 2, wherein the protective gas is nitrogen or an inert gas.
4. The process according to any one of claims 1 to 3, wherein the reactants are added under ice bath conditions.
5. The process according to claim 4, wherein the reaction tube is taken out from the ice bath during the sealing.
6. A process according to any one of claims 2 to 5, wherein said reactants comprise ethylene diphosphine, vinyl ethyl ether and azobisisobutyronitrile.
7. The method according to claim 6, wherein the reactants are added by first adding azobisisobutyronitrile into the reaction tube, and then introducing a shielding gas into the reaction tube to add the other reactants.
8. The process according to claim 7, wherein the reaction mixture is introduced into the reaction tube by introducing a shielding gas to the reaction tube.
9. A reaction apparatus, which is a reaction tube used in the process for producing a bis (ethoxyethylphosphine) according to any one of claims 1 to 8, wherein the reaction tube comprises a housing portion adapted to contain a reactant and a sealing portion adapted to be sealed by sealing.
10. A reactor device according to claim 9, wherein the reactor tube is an integrally formed glass tube.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210379143.2A CN114702522A (en) | 2022-04-12 | 2022-04-12 | Preparation method and reaction device of diethoxyethylphosphane |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210379143.2A CN114702522A (en) | 2022-04-12 | 2022-04-12 | Preparation method and reaction device of diethoxyethylphosphane |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114702522A true CN114702522A (en) | 2022-07-05 |
Family
ID=82174207
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210379143.2A Pending CN114702522A (en) | 2022-04-12 | 2022-04-12 | Preparation method and reaction device of diethoxyethylphosphane |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114702522A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101861170A (en) * | 2007-09-21 | 2010-10-13 | 通用电气健康护理有限公司 | Improved radiopharmaceutical composition |
| WO2015114002A1 (en) * | 2014-01-28 | 2015-08-06 | Rotop Pharmaka Gmbh | Stabilized form of tetrofosmin and its use |
| CN105175367A (en) * | 2015-09-09 | 2015-12-23 | 江苏大学 | Method for converting sugar into 5-HMF (hydroxymethylfurfural) through acid catalysis |
-
2022
- 2022-04-12 CN CN202210379143.2A patent/CN114702522A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101861170A (en) * | 2007-09-21 | 2010-10-13 | 通用电气健康护理有限公司 | Improved radiopharmaceutical composition |
| WO2015114002A1 (en) * | 2014-01-28 | 2015-08-06 | Rotop Pharmaka Gmbh | Stabilized form of tetrofosmin and its use |
| CN105175367A (en) * | 2015-09-09 | 2015-12-23 | 江苏大学 | Method for converting sugar into 5-HMF (hydroxymethylfurfural) through acid catalysis |
Non-Patent Citations (1)
| Title |
|---|
| 张军良，郭燕文: "《有机合成实验方法》", 北京：中国医药科技出版社, pages: 86 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Bertz et al. | Dicyclohexylphosphide as an auxiliary ligand for thermally stable heterocuprates with considerably improved reactivity. The beneficent effect of lithium bromide on cuprate reactivity | |
| JP7254932B2 (en) | System for manufacturing indium phosphide crystals using indium-phosphorus mixture | |
| Tucci et al. | Nickel-mediated formation of thio esters from bound methyl, thiols, and carbon monoxide: A possible reaction pathway of acetyl-coenzyme A synthase activity in nickel-containing carbon monoxide dehydrogenases | |
| Krusic et al. | ESR study of iron carbonyl radical anions | |
| KR910001489B1 (en) | Process for producing high purity zirconium and hafnium | |
| Gunn et al. | The Heats of Formation at 25° of the Crystalline Hydrides and Deuterides and Aqueous Hydroxides of Lithium, Sodium and Potassium1 | |
| CN114702522A (en) | Preparation method and reaction device of diethoxyethylphosphane | |
| Denney et al. | Peroxide route to pentaoxyphosphoranes | |
| List et al. | Carbon suboxide as a C1 reagent. Sequential cleavage of CO from C3O2 at a metal center to give WCl2 (CO)(PMePh2) 2 [C, C':. eta. 2-C (O) CPMePh2] and WCl2 (CO)(PMePh2) 2 (. tplbond. CPMePh2) | |
| Fujiwara et al. | Ph4SbI-catalyzed selective formation of. gamma.-and. sigma.-lactones from oxiranes or oxetanes with ketenes | |
| Gatley et al. | Synthesis of 18F-3-deoxy-3-fluoro-D-glucose with reactor-produced 18F | |
| Bartlett et al. | [20] Purification of farnesylpyrophosphate synthetase by affinity chromatography | |
| CN1173370C (en) | Method for distilling sulfer for preparing radioactive phosphonuclein | |
| Isaev et al. | Lamellar graphite compounds with potassium and benzene: structure and transformations | |
| CN100432082C (en) | Synthesis method of chloro diisopropyl phosphine | |
| CN101333161B (en) | Method for preparing alpha-chloro-fatty acid | |
| US3463605A (en) | Process and apparatus for production of alkali metal monofluorophosphate | |
| Kaupp et al. | Mechanism of solid–solid resolution of pantolactone | |
| CN113387981B (en) | Synthesis method of diethyl phosphite | |
| JPH0810629A (en) | Small-sized concentration flask | |
| US3013863A (en) | Method for the preparation of diborane | |
| WO1991015858A1 (en) | Methods and agents for deuterium/tritium labeling | |
| US3222121A (en) | Preparation of sodium borohydrides | |
| CN114656497B (en) | Preparation method of phenylsilane | |
| FR2647791A1 (en) | PURIFICATION OF BIDENT ORGANOPHOSPHORUS EXTRACTION PRODUCTS |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |