CN108690077A - A kind of synthetic method of the right amine salt of the left phosphine of intermediate - Google Patents
A kind of synthetic method of the right amine salt of the left phosphine of intermediate Download PDFInfo
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- CN108690077A CN108690077A CN201810505937.2A CN201810505937A CN108690077A CN 108690077 A CN108690077 A CN 108690077A CN 201810505937 A CN201810505937 A CN 201810505937A CN 108690077 A CN108690077 A CN 108690077A
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- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 title claims abstract description 38
- 229910000073 phosphorus hydride Inorganic materials 0.000 title claims abstract description 19
- -1 amine salt Chemical class 0.000 title claims abstract description 17
- 238000010189 synthetic method Methods 0.000 title claims abstract description 11
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims abstract description 42
- 239000003054 catalyst Substances 0.000 claims abstract description 31
- 238000006243 chemical reaction Methods 0.000 claims abstract description 30
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims abstract description 21
- RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical compound CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 claims abstract description 20
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims abstract description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 36
- 239000000243 solution Substances 0.000 claims description 23
- 238000003756 stirring Methods 0.000 claims description 21
- 239000000843 powder Substances 0.000 claims description 12
- 239000002904 solvent Substances 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 238000005119 centrifugation Methods 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 238000000643 oven drying Methods 0.000 claims description 6
- XWCIXXXLOAAWPU-NSCUHMNNSA-N [(e)-prop-1-enyl]phosphonic acid Chemical compound C\C=C\P(O)(O)=O XWCIXXXLOAAWPU-NSCUHMNNSA-N 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 3
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 3
- 238000001354 calcination Methods 0.000 claims description 3
- 238000001816 cooling Methods 0.000 claims description 3
- 239000013078 crystal Substances 0.000 claims description 3
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 239000012065 filter cake Substances 0.000 claims description 3
- 238000004900 laundering Methods 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 239000012299 nitrogen atmosphere Substances 0.000 claims description 3
- 229910052573 porcelain Inorganic materials 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 238000002604 ultrasonography Methods 0.000 claims description 3
- 238000010792 warming Methods 0.000 claims description 3
- 238000005406 washing Methods 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 14
- 230000015572 biosynthetic process Effects 0.000 abstract description 13
- 150000003839 salts Chemical class 0.000 abstract description 13
- UFMZWBIQTDUYBN-UHFFFAOYSA-N cobalt dinitrate Chemical compound [Co+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O UFMZWBIQTDUYBN-UHFFFAOYSA-N 0.000 abstract description 12
- 230000000694 effects Effects 0.000 abstract description 8
- LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical compound CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 abstract description 4
- 150000001412 amines Chemical class 0.000 abstract description 3
- 238000006735 epoxidation reaction Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Inorganic materials [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 abstract description 3
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 abstract description 2
- 238000007086 side reaction Methods 0.000 abstract description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 abstract 1
- 229960001484 edetic acid Drugs 0.000 abstract 1
- 239000000047 product Substances 0.000 description 6
- YMDXZJFXQJVXBF-STHAYSLISA-N fosfomycin Chemical compound C[C@@H]1O[C@@H]1P(O)(O)=O YMDXZJFXQJVXBF-STHAYSLISA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 3
- 101100059652 Mus musculus Cetn1 gene Proteins 0.000 description 2
- 101100059655 Mus musculus Cetn2 gene Proteins 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- ODALAXKSIBESFV-PXRNWTNJSA-N [(2r,3s)-3-methyloxiran-2-yl]phosphonic acid;(1r)-1-phenylethanamine Chemical compound C[C@@H]1O[C@@H]1P(O)(O)=O.C[C@@H](N)C1=CC=CC=C1 ODALAXKSIBESFV-PXRNWTNJSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 206010041925 Staphylococcal infections Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- YIYFFLYGSHJWFF-UHFFFAOYSA-N [Zn].N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 Chemical group [Zn].N1C(C=C2N=C(C=C3NC(=C4)C=C3)C=C2)=CC=C1C=C1C=CC4=N1 YIYFFLYGSHJWFF-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 208000015688 methicillin-resistant staphylococcus aureus infectious disease Diseases 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
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
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65502—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a three-membered ring
- C07F9/65505—Phosphonic acids containing oxirane groups; esters thereof
-
- 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
- B01J23/00—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00
- B01J23/70—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper
- B01J23/76—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper combined with metals, oxides or hydroxides provided for in groups B01J23/02 - B01J23/36
- B01J23/80—Catalysts comprising metals or metal oxides or hydroxides, not provided for in group B01J21/00 of the iron group metals or copper combined with metals, oxides or hydroxides provided for in groups B01J23/02 - B01J23/36 with zinc, cadmium or mercury
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a kind of synthetic method of the right amine salt of the left phosphine of intermediate, cis-propene phosphoric acid, α-phenylethylamine, ethylenediamine tetra-acetic acid, Co(NO3)2·6H20,Zn(NO3)2·6H20,2-methylimidazole and NC ZnCo-LDH are primary raw material;The synthesis technology of the present invention carries out epoxidation reaction through hydrogen peroxide under the effect of the catalyst using cis-propene phosphoric acid and α-phenylethylamine and obtains left-handed salt and dextrorotation salt, left-handed salt is may separate out using the different solubility of left-handed salt and dextrorotation salt in absolute ethyl alcohol-water, the i.e. left right amine of phosphine, using the cis-propene phosphoric acid and α-phenylethylamine of NC@ZnCo-LDH catalyst choices being oxidized to after salt, obtain the right amine salt of the left phosphine of intermediate of high-purity, reaction condition is mild, side reaction is few, and the yield of product greatly improves.
Description
Technical field
The present invention relates to a kind of synthetic methods of the right amine salt of the left phosphine of intermediate, belong to chemical industry synthesis field.
Background technology
Phosphonomycin has and does not have not only between unique chemical constitution and antibacterial action mechanism, with other antibiotic or antimicrobial
There is cross resistance, and most present acts synergistically, not only has to common atypia and intracellular pathogenic organisms of respiratory tract strong
Power activity can treat intractable respiratory apparatus infection, serious MRSA and one bacterium mixed infection of P. aeruginosa occurs in lung cancer latter stage
And the critical infection of the patients such as cancer;And with the bioactivity other than very strong antibacterial action.Fosfomycin phenylethylamine calt is a kind of
Medicine intermediate is the important intermediate for synthesizing phosphonomycin salt.Find a kind of method efficiently synthesizing fosfomycin phenylethylamine calt has very much
It is necessary.
Invention content
The purpose of the present invention is to provide a kind of synthetic methods of the right amine salt of the left phosphine of intermediate, and this method is with optimal conditions
It can be catalyzed the reaction of cis-propene phosphoric acid and α-phenylethylamine, there is higher product yield.
A kind of synthetic method of the right amine salt of left phosphine of intermediate, this approach includes the following steps:
Step 1 puts into cis-propene phosphoric acid 12.0g, etoh solvent 10ml into 50ml three-necked flasks, and stirring makes it completely dissolved,
Temperature is controlled at 40 DEG C, and 15.2g α-phenylethylamines are slowly added dropwise, and reaction solution pH is gradually increased, and as pH=6.0, stops being added dropwise;
Being added after crystallizing, which occur, in step 2, the above-mentioned system of stirring contains 1.0gNC ZnCo-LDH catalyst and 0.1g ethylenediamine tetrems
The aqueous solution 0.5ml of acid is heated to 50 DEG C of 30% hydrogen peroxide 16.8g of dropwise addition, and drop, which finishes, is heated to 55 DEG C of reaction 1h;
Step 3, after propylene phosphonic acid completely reaction, it is cooling, stand crystallization, filtering, filter cake is washed with cold absolute ethyl alcohol, with nothing
Water-ethanol-water (4:1) it recrystallizes, filtering obtains the right amine salt of the left phosphine of white, needle-shaped crystals intermediate.
The NC@ZnCo-LDH method for preparing catalyst is as follows:
Step 1 weighs 0.2gCo(NO3)2·6H20 and 0.7gZn(NO3)2·6H20 is scattered in 30ml methanol, is denoted as solution A,
Weigh 1.0g2- methylimidazoles to be scattered in 10ml methanol, be denoted as B solution, A is poured into B, stir after 15min stand for 24 hours, from
The heart, methanol wash 3 times, and oven drying for 24 hours, obtains purple powder ZnCoZIF;
Above-mentioned purple powder is transferred in porcelain boat by step 2, is put into tube furnace, and calcination under nitrogen atmosphere is warming up to 900
DEG C, 3h is kept the temperature, taking-up sample is cooled to room temperature, obtains black powder Co/NC;
Step 3 weighs 50mgCo/NC in the salpeter solution of 4mol/L, and ultrasound reflux 90min, centrifugation, massive laundering are washed to molten
Liquid is in neutrality, and oven drying for 24 hours, obtains black powder NC;
Step 4 weighs 40mgNC and is scattered in 3ml aqueous solutions, ultrasonic 30min, is charged with 8ml methanol, ultrasonic 30min,
Continuously add 0.3gCo(NO3)2·6H20 and 0.3g2- methylimidazoles stir 10min, stand 2h, and centrifugation, washing, drying obtain
To NC@ZnCo-LDH catalyst.
Advantageous effect:The present invention provides a kind of synthetic method of the right amine salt of the left phosphine in centre, cis-propene phosphoric acid and α-benzene second
Amine carries out epoxidation reaction through hydrogen peroxide under the effect of the catalyst and obtains left-handed salt and dextrorotation salt, is existed using left-handed salt and dextrorotation salt
Different solubility in absolute ethyl alcohol-water may separate out left-handed salt, i.e., the left right amine of phosphine;Propylene phosphonic acid is a kind of unsaturated acids,
Its epoxidation is the committed step in phosphonomycin synthesis, and traditional phosphonomycin asymmetric syntheses is using propylene phosphonic acid as starting material
It carries out.They are chiral zinc porphyrin group using tartaric acid, by optically pure phosphonomycin, synthetic method have been obtained by the reaction as follows
Not only step is more, and yield is low, and enantioselectivity is poor;This technique is oxidized to using NC@ZnCo-LDH catalyst choices
Cis-propene phosphoric acid after salt and α-phenylethylamine obtain the right amine salt of the left phosphine of intermediate of high-purity, and reaction condition is mild, side reaction
Few, the yield of product greatly improves.
Specific implementation mode
Embodiment 1
A kind of synthetic method of the right amine salt of left phosphine of intermediate, this approach includes the following steps:
Step 1 puts into cis-propene phosphoric acid 12.0g, etoh solvent 10ml into 50ml three-necked flasks, and stirring makes it completely dissolved,
Temperature is controlled at 40 DEG C, and 15.2g α-phenylethylamines are slowly added dropwise, and reaction solution pH is gradually increased, and as pH=6.0, stops being added dropwise;
Being added after crystallizing, which occur, in step 2, the above-mentioned system of stirring contains 1.0gNC ZnCo-LDH catalyst and 0.1g ethylenediamine tetrems
The aqueous solution 0.5ml of acid is heated to 50 DEG C of 30% hydrogen peroxide 16.8g of dropwise addition, and drop, which finishes, is heated to 55 DEG C of reaction 1h;
Step 3, after propylene phosphonic acid completely reaction, it is cooling, stand crystallization, filtering, filter cake is washed with cold absolute ethyl alcohol, with nothing
Water-ethanol-water (4:1) it recrystallizes, filtering obtains the right amine salt of the left phosphine of white, needle-shaped crystals intermediate.
The NC@ZnCo-LDH method for preparing catalyst is as follows:
Step 1 weighs 0.2gCo(NO3)2·6H20 and 0.7gZn(NO3)2·6H20 is scattered in 30ml methanol, is denoted as solution A,
Weigh 1.0g2- methylimidazoles to be scattered in 10ml methanol, be denoted as B solution, A is poured into B, stir after 15min stand for 24 hours, from
The heart, methanol wash 3 times, and oven drying for 24 hours, obtains purple powder ZnCoZIF;
Above-mentioned purple powder is transferred in porcelain boat by step 2, is put into tube furnace, and calcination under nitrogen atmosphere is warming up to 900
DEG C, 3h is kept the temperature, taking-up sample is cooled to room temperature, obtains black powder Co/NC;
Step 3 weighs 50mgCo/NC in the salpeter solution of 4mol/L, and ultrasound reflux 90min, centrifugation, massive laundering are washed to molten
Liquid is in neutrality, and oven drying for 24 hours, obtains black powder NC;
Step 4 weighs 40mgNC and is scattered in 3ml aqueous solutions, ultrasonic 30min, is charged with 8ml methanol, ultrasonic 30min,
Continuously add 0.3gCo(NO3)2·6H20 and 0.3g2- methylimidazoles stir 10min, stand 2h, and centrifugation, washing, drying obtain
To NC@ZnCo-LDH catalyst.
Embodiment 2
Step 1 puts into cis-propene phosphoric acid 10.0g, etoh solvent 10ml into 50ml three-necked flasks, and stirring makes it completely dissolved,
Temperature is controlled at 40 DEG C, and 15.2g α-phenylethylamines are slowly added dropwise, and reaction solution pH is gradually increased, and as pH=6.0, stops being added dropwise;Its
Remaining step is the same as embodiment 1.
Embodiment 3
Step 1 puts into cis-propene phosphoric acid 8.0g, etoh solvent 10ml into 50ml three-necked flasks, and stirring makes it completely dissolved, temperature
15.2g α-phenylethylamines are slowly added dropwise at 40 DEG C in degree control, and reaction solution pH is gradually increased, and as pH=6.0, stop being added dropwise;Remaining
Step is the same as embodiment 1.
Embodiment 4
Step 1 puts into cis-propene phosphoric acid 6.0g, etoh solvent 10ml into 50ml three-necked flasks, and stirring makes it completely dissolved, temperature
15.2g α-phenylethylamines are slowly added dropwise at 40 DEG C in degree control, and reaction solution pH is gradually increased, and as pH=6.0, stop being added dropwise;Remaining
Step is the same as embodiment 1.
Embodiment 5
Step 1 puts into cis-propene phosphoric acid 4.0g, etoh solvent 10ml into 50ml three-necked flasks, and stirring makes it completely dissolved, temperature
15.2g α-phenylethylamines are slowly added dropwise at 40 DEG C in degree control, and reaction solution pH is gradually increased, and as pH=6.0, stop being added dropwise;Remaining
Step is the same as embodiment 1.
Embodiment 6
Step 1 puts into cis-propene phosphoric acid 12.0g, etoh solvent 10ml into 50ml three-necked flasks, and stirring makes it completely dissolved,
Temperature is controlled at 40 DEG C, and 13.2g α-phenylethylamines are slowly added dropwise, and reaction solution pH is gradually increased, and as pH=6.0, stops being added dropwise;Its
Remaining step is the same as embodiment 1.
Embodiment 7
Step 1 puts into cis-propene phosphoric acid 12.0g, etoh solvent 10ml into 50ml three-necked flasks, and stirring makes it completely dissolved,
Temperature is controlled at 40 DEG C, and 11.2g α-phenylethylamines are slowly added dropwise, and reaction solution pH is gradually increased, and as pH=6.0, stops being added dropwise;Its
Remaining step is the same as embodiment 1.
Embodiment 8
Step 1 puts into cis-propene phosphoric acid 12.0g, etoh solvent 10ml into 50ml three-necked flasks, and stirring makes it completely dissolved,
Temperature is controlled at 40 DEG C, and 9.2g α-phenylethylamines are slowly added dropwise, and reaction solution pH is gradually increased, and as pH=6.0, stops being added dropwise;Remaining
Step is the same as embodiment 1.
Embodiment 9
Step 1 puts into cis-propene phosphoric acid 12.0g, etoh solvent 10ml into 50ml three-necked flasks, and stirring makes it completely dissolved,
Temperature is controlled at 40 DEG C, and 7.2g α-phenylethylamines are slowly added dropwise, and reaction solution pH is gradually increased, and as pH=6.0, stops being added dropwise;Remaining
Step is the same as embodiment 1.
Embodiment 10
Step 1 puts into cis-propene phosphoric acid 12.0g, etoh solvent 10ml into 50ml three-necked flasks, and stirring makes it completely dissolved,
Temperature is controlled at 40 DEG C, and 5.2g α-phenylethylamines are slowly added dropwise, and reaction solution pH is gradually increased, and as pH=6.0, stops being added dropwise;Remaining
Step is the same as embodiment 1.
Reference examples 1
It is with 1 difference of embodiment:In the synthesis step 2 of intermediate, use the Co/NC of equivalent as catalyst, remaining step
It is identical with embodiment 1.
Reference examples 2
It is with 1 difference of embodiment:In the synthesis step 2 of intermediate, catalyst is not added, remaining step and embodiment 1
It is identical.
Reference examples 3
It is with 1 difference of embodiment:In the synthesis step 1 of catalyst, Co is not added(NO3)2·6H20, remaining step with
Embodiment 1 is identical.
Reference examples 4
It is with 1 difference of embodiment:In the synthesis step 1 of catalyst, Zn is not added(NO3)2·6H20, remaining step with
Embodiment 1 is identical.
Reference examples 5
It is with 1 difference of embodiment:In the synthesis step 1 of catalyst, Co(NO3)2·6H20 and Zn(NO3)2·6H20 mass
Than being 7:2, remaining step is identical with embodiment 1.
Reference examples 6
It is with 1 difference of embodiment:In the synthesis step 1 of catalyst, Co(NO3)2·6H20 and Zn(NO3)2·6H20 mass
Than being 1:1, remaining step is identical with embodiment 1.
Reference examples 7
It is with 1 difference of embodiment:In the synthesis step 3 of catalyst, 50mgCo/NC is weighed in the hydrochloric acid solution of 4mol/L
In;Remaining step is identical with embodiment 1.
Reference examples 8
It is with 1 difference of embodiment:In the synthesis step 3 of catalyst, 50mgCo/NC is weighed in the sulfuric acid solution of 4mol/L
In;Remaining step is identical with embodiment 1.
Reference examples 9
It is with 1 difference of embodiment:In the synthesis step 2 of catalyst, Co(NO3)2·6H20 and 2-methylimidazole mass ratio 4:
1, remaining step is identical with embodiment 1.
Reference examples 10
It is with 1 difference of embodiment:In the synthesis step 2 of catalyst, Co(NO3)2·6H20 and 2-methylimidazole mass ratio 1:
4, remaining step is identical with embodiment 1.
It is as shown in the table for reaction result under embodiment and reference examples different condition
| The left right amine salt yield/% of phosphine | |
| Embodiment 1 | 99.8 |
| Embodiment 2 | 98.3 |
| Embodiment 3 | 82.4 |
| Embodiment 4 | 67.5 |
| Embodiment 5 | 63.1 |
| Embodiment 6 | 77.4 |
| Embodiment 7 | 72.1 |
| Embodiment 8 | 83.7 |
| Embodiment 9 | 66.4 |
| Embodiment 10 | 73.3 |
| Reference examples 1 | 40.1 |
| Reference examples 2 | 31.9 |
| Reference examples 3 | 43.1 |
| Reference examples 4 | 46.2 |
| Reference examples 5 | 58.5 |
| Reference examples 6 | 60.1 |
| Reference examples 7 | 57.2 |
| Reference examples 8 | 46.3 |
| Reference examples 9 | 39.7 |
| Reference examples 10 | 53.0 |
The experimental results showed that catalyst has good catalytic effect to the synthetic reaction of cis-propene phosphoric acid and α-phenylethylamine, anti-
One timing of condition is answered, intermediate yield is higher, and catalytic performance is better, otherwise poorer;Cis-propene phosphoric acid, α-phenylethylamine mass ratio are
At embodiment 1,2, synthetic effect is best, with embodiment 1 the difference lies in that embodiment 3 changes mainly respectively to embodiment 10
The dosage and proportioning of raw material cis-propene phosphoric acid, α-phenylethylamine, have the yield of synthetic product different influences;Reference examples 1 are to right
2 composite catalyst not being added and uses Co/NC as catalyst, other steps are identical, cause product yield apparent as usual
It reduces, it is very big to illustrate that the product of composite catalyst reaction influences;Reference examples 3 to reference examples 6 change Co(NO3)2·6H20 and Zn
(NO3)2·6H20 dosage, effect is still bad, illustrates that two kinds of metal salts are essential raw materials in catalyst;Reference examples 7 to
The hydrochloric acid of reference examples 8 and sulfuric acid substitution nitric acid carry out sour processing, are catalyzed the variation with obvious effects of reaction, illustrate nitric acid to catalyst
Improvement is preferable;Reference examples 9 are to reference examples 10Co(NO3)2·6H20 and 2-methylimidazole mass ratio change, catalyst
Structure change, the conversion ratio of reaction and selectivity are very low, and reaction effect is obviously deteriorated, and product yield is not still high;Cause
This has excellent catalytic effect using the catalyst of the present invention to the synthetic reaction of the right amine salt of the left phosphine of intermediate.
Claims (2)
1. a kind of synthetic method of the right amine salt of left phosphine of intermediate, it is characterised in that this approach includes the following steps:
Step 1 puts into cis-propene phosphoric acid 12.0g, etoh solvent 10ml into 50ml three-necked flasks, and stirring makes it completely dissolved,
Temperature is controlled at 40 DEG C, and 15.2g α-phenylethylamines are slowly added dropwise, and reaction solution pH is gradually increased, and as pH=6.0, stops being added dropwise;
Being added after crystallizing, which occur, in step 2, the above-mentioned system of stirring contains 1.0gNC ZnCo-LDH catalyst and 0.1g ethylenediamine tetrems
The aqueous solution 0.5ml of acid is heated to 50 DEG C of 30% hydrogen peroxide 16.8g of dropwise addition, and drop, which finishes, is heated to 55 DEG C of reaction 1h;
Step 3, after propylene phosphonic acid completely reaction, it is cooling, stand crystallization, filtering, filter cake is washed with cold absolute ethyl alcohol, with nothing
Water-ethanol-water (4:1) it recrystallizes, filtering obtains the right amine salt of the left phosphine of white, needle-shaped crystals intermediate.
2. the synthetic method of the right amine salt of the left phosphine of a kind of intermediate according to claim 1, which is characterized in that
The NC@ZnCo-LDH method for preparing catalyst is as follows:
Step 1 weighs 0.2gCo(NO3)2·6H20 and 0.7gZn(NO3)2·6H20 is scattered in 30ml methanol, is denoted as solution A,
Weigh 1.0g2- methylimidazoles to be scattered in 10ml methanol, be denoted as B solution, A is poured into B, stir after 15min stand for 24 hours, from
The heart, methanol wash 3 times, and oven drying for 24 hours, obtains purple powder ZnCoZIF;
Above-mentioned purple powder is transferred in porcelain boat by step 2, is put into tube furnace, and calcination under nitrogen atmosphere is warming up to 900
DEG C, 3h is kept the temperature, taking-up sample is cooled to room temperature, obtains black powder Co/NC;
Step 3 weighs 50mgCo/NC in the salpeter solution of 4mol/L, and ultrasound reflux 90min, centrifugation, massive laundering are washed to molten
Liquid is in neutrality, and oven drying for 24 hours, obtains black powder NC;
Step 4 weighs 40mgNC and is scattered in 3ml aqueous solutions, ultrasonic 30min, is charged with 8ml methanol, ultrasonic 30min,
Continuously add 0.3gCo(NO3)2·6H20 and 0.3g2- methylimidazoles stir 10min, stand 2h, and centrifugation, washing, drying obtain
To NC@ZnCo-LDH catalyst.
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