CN108774261B - Preparation method of deuterated methyl parathion - Google Patents
Preparation method of deuterated methyl parathion Download PDFInfo
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- CN108774261B CN108774261B CN201810727865.6A CN201810727865A CN108774261B CN 108774261 B CN108774261 B CN 108774261B CN 201810727865 A CN201810727865 A CN 201810727865A CN 108774261 B CN108774261 B CN 108774261B
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- RLBIQVVOMOPOHC-UHFFFAOYSA-N parathion-methyl Chemical class COP(=S)(OC)OC1=CC=C([N+]([O-])=O)C=C1 RLBIQVVOMOPOHC-UHFFFAOYSA-N 0.000 title claims abstract description 43
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 claims abstract description 62
- 239000007795 chemical reaction product Substances 0.000 claims abstract description 61
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 claims abstract description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 60
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 45
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 42
- 239000012074 organic phase Substances 0.000 claims description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 27
- 238000003756 stirring Methods 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 12
- 239000003208 petroleum Substances 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 10
- 238000001914 filtration Methods 0.000 claims description 10
- 239000007788 liquid Substances 0.000 claims description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 8
- 238000000926 separation method Methods 0.000 claims description 8
- 238000004809 thin layer chromatography Methods 0.000 claims description 8
- 238000004440 column chromatography Methods 0.000 claims description 7
- 238000000605 extraction Methods 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 7
- 150000007529 inorganic bases Chemical class 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- 239000003480 eluent Substances 0.000 claims description 4
- 238000010438 heat treatment Methods 0.000 claims description 4
- 239000005457 ice water Substances 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- 238000012544 monitoring process Methods 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 239000012071 phase Substances 0.000 claims description 2
- BMDVPRGEZHHGLJ-UHFFFAOYSA-N [S](Cl)(Cl)Cl.[P] Chemical compound [S](Cl)(Cl)Cl.[P] BMDVPRGEZHHGLJ-UHFFFAOYSA-N 0.000 abstract description 5
- 238000000034 method Methods 0.000 abstract description 4
- 239000000047 product Substances 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 2
- 239000000126 substance Substances 0.000 description 13
- 238000005481 NMR spectroscopy Methods 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 239000000243 solution Substances 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 239000008399 tap water Substances 0.000 description 3
- 235000020679 tap water Nutrition 0.000 description 3
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000005886 esterification reaction Methods 0.000 description 2
- 231100000086 high toxicity Toxicity 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
- 239000000575 pesticide Substances 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- WQYSXVGEZYESBR-UHFFFAOYSA-N thiophosphoryl chloride Chemical group ClP(Cl)(Cl)=S WQYSXVGEZYESBR-UHFFFAOYSA-N 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- QCJQWJKKTGJDCM-UHFFFAOYSA-N [P].[S] Chemical compound [P].[S] QCJQWJKKTGJDCM-UHFFFAOYSA-N 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- OKKJLVBELUTLKV-MICDWDOJSA-N deuteriomethanol Chemical compound [2H]CO OKKJLVBELUTLKV-MICDWDOJSA-N 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- -1 inorganic base potassium carbonate Chemical class 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000003986 organophosphate insecticide Substances 0.000 description 1
- 239000003987 organophosphate pesticide Substances 0.000 description 1
- LCCNCVORNKJIRZ-UHFFFAOYSA-N parathion Chemical compound CCOP(=S)(OCC)OC1=CC=C([N+]([O-])=O)C=C1 LCCNCVORNKJIRZ-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
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- 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
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/16—Esters of thiophosphoric acids or thiophosphorous acids
- C07F9/165—Esters of thiophosphoric acids
- C07F9/18—Esters of thiophosphoric acids with hydroxyaryl compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/004—Acyclic, carbocyclic or heterocyclic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen, sulfur, selenium or tellurium
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/05—Isotopically modified compounds, e.g. labelled
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- 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)
Abstract
The invention discloses a preparation method of deuterated methyl parathion, which comprises the following steps: (1) Mono-esterifying trichloro sulfur phosphorus and deuterated methanol to obtain a reaction product II; (2) Esterifying the reaction product II with p-nitrophenol to obtain a reaction product IV; (3) And esterifying the reaction product IV with deuterated methanol to obtain a reaction product V, wherein the reaction product V is deuterated methyl parathion. The invention provides a new method for synthesizing the deuterated methyl parathion, which has the advantages of mild reaction conditions, simple operation, good quality of the obtained deuterated methyl parathion product, good stability and the like.
Description
Technical Field
The invention relates to the technical field of chemical analysis. In particular to a preparation method of deuterated methyl parathion.
Background
Methyl parathion is commonly called methyl 1605 (a compound Va in a formula), has a scientific name of O, O-dimethyl-O- (4-nitrophenyl) thiophosphate, is an organophosphorus insecticide, and belongs to high-toxicity pesticides. China is a big agricultural country, the pesticide consumption is large, and the organophosphorus pesticide has wide application range and high toxicity. This requires the police department of accreditation to test sample samples related to this class of drugs. In order to ensure that a detection method is prepared and reliable, an internal standard substance is added during detection, and a corresponding deuterated substance is the best internal standard substance, and the application of the internal standard substance is non-civil and has particularity, so that research and production of commodities in China are relatively less, and the standard substance is necessary and indispensable in analysis and detection. The stability of the deuterated internal standard substance is poor, china has not broken through the technical bottleneck restricting the production of the deuterated substance in China, no manufacturer producing the deuterated substance involved in the case is available, and the product can only be imported. For a long time, deuterated internal standard substances used in China are imported dependently, and the imported substances are solutions instead of solid powder, and the price is high, so that the wide application of the standard substances in China is severely limited.
There is currently no complete detailed literature on the synthesis of deuterated methyl parathion (compound V). Therefore, the development of a new process for synthesizing deuterated methyl parathion with self-known property rights is urgently needed.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is a preparation method of deuterated methyl parathion.
In order to solve the technical problems, the invention provides the following technical scheme:
a preparation method of deuterated methyl parathion comprises the following steps:
(1) Mono-esterifying trichloro sulfur phosphorus and deuterated methanol to obtain a reaction product II;
(2) Esterifying the reaction product II with p-nitrophenol to obtain a reaction product IV;
(3) And esterifying the reaction product IV with deuterated methanol to obtain a reaction product V, wherein the reaction product V is deuterated methyl parathion.
The preparation method of the deuterium-substituted methyl parathion comprises the following steps:
(1) Performing a mono-esterification reaction on trichlorothiophosphoryl and deuterated methanol at a temperature of between 10 ℃ below zero and 5 ℃ below zero to obtain a reaction product II, wherein the reaction product II is O- (methyl-D3) -thiophosphoryl dichloride;
(2) Dissolving a reaction product II and p-nitrophenol with equal substance amount in an organic solvent, adding inorganic base, and esterifying the reaction product II and the p-nitrophenol at room temperature to obtain a reaction product IV, wherein the reaction product IV is O- (methyl-D3) -O- (4-nitrophenyl) -thiophosphoryl amide as shown in the following formula;
(3) Dropwise adding a deuterated methanol solution of NaOH at-5 ℃ to perform esterification to obtain a reaction product V, wherein the reaction product V is deuterated methyl parathion as shown in the following formula;
in the preparation method of the deuterated methyl parathion, in the step (1), the mass ratio of the deuterated methanol to the trichlorothiophosphoryl is 3.
In the preparation method of the deuterium methyl parathion, in the step (2), the inorganic base is K 2 CO 3 And Na 2 CO 3 One or more of (a).
In the preparation method of the deuterium-substituted methyl parathion, in the step (2), the ratio of the amount of the reaction product II to the amount of the inorganic base is 1.
In the preparation method of the deuterated methyl parathion, in the step (2), the organic solvent is one or more of tetrahydrofuran, diethyl ether and 1, 4-dioxane.
In the preparation method of the deuterated methyl parathion, in the step (3), the mass ratio of NaOH to the reaction product IV is 5.
In the preparation method of the deuterated methyl parathion, in the step (3), the mass ratio of the deuterated methanol to the reaction product IV is 4.
The preparation method of the deuterium-substituted methyl parathion comprises the following steps:
(1) Placing 122.4mmol of trichlorosulfur phosphorus in a 100mL round-bottom flask, cooling an ice salt bath to-10 to-5 ℃, then dropwise adding 367.2mmol of deuterated methanol, after dropwise adding is finished for 15-20min, heating to-5 ℃, continuing stirring for reaction for 1h, adding 50mL of ice water into a reaction system, stirring for 5min, separating, retaining an organic phase after liquid separation, extracting a water phase after liquid separation twice with dichloromethane, extracting with 20mL of dichloromethane each time, then combining the organic phase after liquid separation and the organic phase obtained by extraction, drying with 25g of anhydrous magnesium sulfate, filtering, and concentrating under reduced pressure to obtain a reaction product II;
(2) Placing 115.5mmol of a reaction product II in a 100mL round-bottom flask, adding 30mL of an organic solvent, stirring until the reaction product II is dissolved, then adding 116.45mmol of p-nitrophenol, adding 115.5mmol of inorganic base in 3 batches under stirring, stirring at room temperature for 1h, then adding 60mL of water into a reaction system, then extracting for 3 times by using dichloromethane, extracting for 50mL of dichloromethane each time, combining extracted organic phases, drying by using 30g of anhydrous magnesium sulfate, filtering, reducing pressure and concentrating, purifying by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 15;
(3) Placing 7.3mmol of reaction product IV in a 10mL round-bottom flask, cooling to-5 ℃ in an ice salt bath, dropwise adding a mixed solution of deuterated methanol and NaOH, wherein the mixed solution of deuterated methanol and NaOH is 37mmol of NaOH dissolved in 8.0g of deuterated methanol, and dropwise adding for 15 min; keeping the reaction temperature at-5 ℃, continuing stirring for 2h, monitoring the reaction by thin-layer chromatography (TLC) until a reaction product IV disappears, recovering deuterated methanol, adding 20mL of water into the reaction system, extracting with ethyl acetate for 3 times, extracting with 20mL of ethyl acetate each time, combining the extracted organic phases, washing the organic phases with 1% diluted hydrochloric acid by volume fraction, drying the organic phases with 20g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, purifying by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 15.
The preparation method of the deuterium-substituted methyl parathion is characterized in that the electrodeless alkali is Na 2 CO 3 Or K 2 CO 3 The organic solvent is tetrahydrofuran or 1, 4-dioxane.
The technical scheme of the invention achieves the following beneficial technical effects:
the preparation method of the deuterated methyl parathion has the advantages of mild reaction conditions, simple operation, good quality of the obtained deuterated methyl parathion product, good stability and the like.
Drawings
FIG. 1 is a synthetic scheme of a process for the preparation of deuterated methyl parathion according to the present invention;
FIG. 2 is a nuclear magnetic resonance hydrogen spectrogram of deuterated methyl parathion in the preparation method of deuterated methyl parathion;
FIG. 3 is a nuclear magnetic resonance phosphorus spectrum of deuterated methyl parathion according to the preparation method of deuterated methyl parathion;
FIG. 4 is a mass spectrum of deuterated methyl parathion in the preparation method of deuterated methyl parathion of the present invention;
FIG. 5 is a high performance liquid chromatogram of deuterated methyl parathion prepared by the preparation method of deuterated methyl parathion.
The reference numbers in the figures denote: i-trichloro sulfur phosphorus; II-O- (methyl-D3) -thiophosphoryl dichloride; III-p-nitrophenol; IV-O- (methyl-D3) -O- (4-nitrophenyl) -thiophosphoramide; v-deuterated methyl parathion.
Detailed Description
Deuterated methyl parathion as shown in the formula; CAS number: 96740-32-8.
Example 1
(1) Mono-esterifying trichloro sulfur phosphorus and deutero methanol to obtain reaction product II (molecular weight 169.979)
Weighing 20.8 g of phosphorus trichloride (compound I,122.4 mmol) and placing the phosphorus trichloride in a 100mL round-bottom flask, cooling the temperature of an ice salt bath to-10 ℃, then dropwise adding 13.3 g of deuterated methanol (367.2 mmol), after dropwise adding for 15-20min, heating to-5 ℃, continuing stirring for reaction for 1h, adding 50mL of ice water (water at 0 ℃) into the reaction system, stirring for 5min, separating, retaining the organic phase after separating, and extracting the aqueous phase after separating twice with dichloromethane, wherein 20mL of dichloromethane is used for extracting each time. And combining the organic phase after liquid separation and the organic phase obtained by extraction, drying with 25g of anhydrous magnesium sulfate, filtering, and concentrating under reduced pressure to obtain a reactant II, namely O- (methyl-D3) -thiophosphoryl dichloride.
(2) Esterifying the reaction product II with p-nitrophenol to obtain a reaction product IV
19.4g of reaction product II (115.5 mmol) are taken in a 100mL round-bottom flask, 30mL of tetrahydrofuran are added and stirred until dissolution, 16.2g of p-nitrophenol (139.11 molecular weight, formula III, 116.45 mmol) are subsequently added, 15.9g of the inorganic base potassium carbonate (115.5 mmol) are added in 3 portions with stirring at intervals of 0.5h, the reaction is stirred at room temperature for 1h, 60mL of tap water are subsequently added to the reaction system and the mixture is extracted 3 times with 50mL of dichloromethane each time, the organic phases after extraction are combined, dried over 30g of anhydrous magnesium sulfate, filtered and concentrated under reduced pressure and purified by column chromatography (PE: EA = EA 15, PE is petroleum ether, EA is ethyl acetate and the volume ratio of PE to PA is 15) to give 28g of reaction product IV, O- (methyl-D3) -O- (4-nitrophenyl) -thiophosphoryl amide.
(3) And esterifying the reaction product IV with deuterated methanol to obtain a reaction product V, wherein the reaction product V is deuterated methyl parathion.
Placing 2.0g of reaction product IV (7.3 mmol, molecular weight 272.639) in a 10mL round-bottom flask, cooling to-5 ℃ in an ice salt bath, dropwise adding a deuterated methanol solution of NaOH, wherein the deuterated methanol solution of NaOH is prepared by dissolving 37mmol of NaOH (1.48 g) in 8.0g of deuterated methanol, and finishing dropwise adding for 15 min; keeping the reaction temperature at-5 ℃, continuing stirring for 2h, monitoring the reaction by thin-layer chromatography (TLC) until a reaction product IV disappears, recovering deuterated methanol, adding 20mL of water into the reaction system, extracting with ethyl acetate for 3 times, extracting with 20mL of ethyl acetate each time, combining the extracted organic phases, washing the organic phases with 1% by mass of dilute hydrochloric acid, drying the organic phases with 20g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, and purifying by column chromatography (PE: EA = 15, PE is petroleum ether, EA is ethyl acetate, and the volume ratio of PE to EA is 15) to obtain a reaction product V, wherein the mass of the reaction product V is 1.7g, and the yield is 85%.
Example 2
(1) Mono-esterifying trichloro-sulfur phosphorus and deuterated methanol to obtain reaction product II
Weighing 20.8 g of phosphorus trichloride (compound I,122.4 mmol) and placing the phosphorus trichloride in a 100mL round-bottom flask, cooling the temperature of an ice salt bath to-10 ℃, then dropwise adding 13.3 g of deuterated methanol (367.2 mmol), after dropwise adding for 15-20min, heating to-5 ℃, continuing stirring for reaction for 1h, adding 50mL of ice water (water at 0 ℃) into the reaction system, stirring for 5min, separating, retaining the organic phase after separating, and extracting the aqueous phase after separating twice with dichloromethane, wherein 20mL of dichloromethane is used for extraction each time. And combining the organic phase after liquid separation and the organic phase obtained by extraction, drying with 25g of anhydrous magnesium sulfate, filtering, and concentrating under reduced pressure to obtain a reactant II, namely O- (methyl-D3) -thiophosphoryl dichloride.
(2) Esterifying the reaction product II with p-nitrophenol to obtain a reaction product IV
19.4g of reaction product II (115.5 mmol) is taken and placed in a 100mL round-bottom flask, 30mL of organic solvent 1, 4-dioxane is added and stirred until dissolution, then 16.2g of p-nitrophenol (compound formula III, 116.45 mmol) is added, 12.2g of sodium carbonate (115.1 mmol, molecular weight 105.99) is added in 3 portions under stirring, the reaction is stirred at room temperature for 1h each time, then 60mL of tap water is added to the reaction system, and then extraction is carried out for 3 times with dichloromethane, 50mL of dichloromethane is used each time, the extracted organic phases are combined, dried by 30g of anhydrous magnesium sulfate, filtered and concentrated under reduced pressure, and purified (PE: EA = 15, PE is petroleum ether, EA is ethyl acetate, the volume ratio of PE to PA is 15), 27g of reaction product IV is obtained, and the reaction product IV is O- (methyl-D3) -O- (4-nitrophenyl) -thiophosphoryl amide.
(3) And esterifying the reaction product IV with deuterated methanol to obtain a reaction product V, wherein the reaction product V is deuterated methyl parathion.
Placing 2.0g of reaction product IV (7.3 mmol, molecular weight 272.639) in a 10mL round-bottom flask, cooling to-5 ℃ in an ice salt bath, dropwise adding a deuterated methanol solution of NaOH, wherein the deuterated methanol solution of NaOH is prepared by dissolving 37mmol of NaOH (1.48 g) in 8.0g of deuterated methanol, and finishing dropwise adding for 15 min; keeping the reaction temperature at-5 ℃, continuing stirring for 2h, monitoring the reaction by thin-layer chromatography (TLC) until a reaction product IV disappears, recovering deuterated methanol, adding 20mL of tap water into the reaction system, extracting with ethyl acetate for 3 times, extracting with 20mL of ethyl acetate each time, combining the extracted organic phases, washing the organic phases with 1% diluted hydrochloric acid by mass fraction, drying the organic phases with 20g of anhydrous magnesium sulfate, filtering and concentrating under reduced pressure, and purifying by column chromatography (PE: EA = 15, PE is petroleum ether, PA is ethyl acetate, the volume ratio of PE to EA is 15).
And respectively adopting a nuclear magnetic resonance hydrogen spectrum, a nuclear magnetic resonance phosphorus spectrum, a mass spectrum and a high performance liquid chromatography to characterize the prepared deuterated methyl parathion. The method comprises the following specific steps:
as shown in fig. 2, nuclear magnetic resonance hydrogen spectrum: 1 H NMR (300 MHz, Chloroform-d) δ 7.28-7.34 (m, 2H), 8.21-8.25 (m, 2H); the synthesized compound only contains 4H on a benzene ring, and H on a methyl group is completely deuterated.
As shown in fig. 3, nmr phospho-spectrum: 1 P NMR (121 MHz, CDCl 3 ) δ 66.1; indicating that the synthesized compound contains P.
As shown in fig. 4, mass spectrum: HRMS (ESI) calcd. For C 8 H 5 D 6 NO 5 PS [M + H] + 270.0467, found: 270.0471。
As shown in fig. 5, at 5.129s, a retained peak of deuteromethyl parathion appears.
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 are possible which remain within the scope of the appended claims.
Claims (1)
1. A preparation method of deuterated methyl parathion is characterized by comprising the following steps:
(1) Placing 122.4mmol of phosphorus trichloride in a 100mL round bottom flask, cooling to-10 to-5 ℃ in an ice salt bath, then dropwise adding 367.2mmol of deuterated methanol, after 15-20min of dropwise addition is finished, heating to-5 ℃, continuing stirring for reaction for 1h, adding 50mL of ice water into a reaction system, stirring for 5min, separating liquid, retaining an organic phase after liquid separation, extracting a water phase after liquid separation twice with dichloromethane, extracting with 20mL of dichloromethane each time, then combining the organic phase after liquid separation and the organic phase obtained by extraction, drying with 25g of anhydrous magnesium sulfate, filtering, and concentrating under reduced pressure to obtain a reaction product II; the reaction product II is O- (methyl-D3) -thiophosphoryl dichloride;
(2) Placing 115.5mmol of a reaction product II in a 100mL round-bottom flask, adding 30mL of an organic solvent, stirring until the reaction product II is dissolved, then adding 116.45mmol of p-nitrophenol, adding 115.5mmol of inorganic base in 3 batches under stirring, stirring at room temperature for 1h, then adding 60mL of water into a reaction system, then extracting for 3 times by using dichloromethane, extracting for 50mL of dichloromethane each time, combining extracted organic phases, drying by using 30g of anhydrous magnesium sulfate, filtering, reducing pressure and concentrating, purifying by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 15; the reaction product IV is O- (methyl-D3) -O- (4-nitrophenyl) -thiophosphoramide;
(3) Placing 7.3mmol of reaction product IV in a 10mL round-bottom flask, cooling to-5 ℃ in an ice salt bath, dropwise adding a mixed solution of deuterated methanol and NaOH, wherein the mixed solution of deuterated methanol and NaOH is 37mmol of NaOH dissolved in 8.0g of deuterated methanol, and dropwise adding for 15 min; keeping the reaction temperature at-5 ℃, continuing stirring for reaction for 2 hours, monitoring the reaction by thin-layer chromatography (TLC) until a reaction product IV disappears, recovering deuterated methanol, adding 20mL of water into the reaction system, extracting with ethyl acetate for 3 times, extracting with 20mL of ethyl acetate each time, combining the extracted organic phases, washing the organic phase with 1% diluted hydrochloric acid by volume fraction, drying the organic phase with 20g of anhydrous magnesium sulfate, filtering, concentrating under reduced pressure, purifying by column chromatography, wherein an eluent is a mixture of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is 15 to obtain a reaction product V, wherein the reaction product V is deuterated methyl parathion as shown in the following formula;
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| CN103288872A (en) * | 2012-03-03 | 2013-09-11 | 北京勤邦生物技术有限公司 | Methyl parathion hapten, and preparation method and application thereof |
| CN106866729A (en) * | 2017-02-13 | 2017-06-20 | 湘潭大学 | Phosphorus thiochloride prepares the method and apparatus of O methyl thio-phosphoryl dichlorides |
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| CN103288872A (en) * | 2012-03-03 | 2013-09-11 | 北京勤邦生物技术有限公司 | Methyl parathion hapten, and preparation method and application thereof |
| CN106866729A (en) * | 2017-02-13 | 2017-06-20 | 湘潭大学 | Phosphorus thiochloride prepares the method and apparatus of O methyl thio-phosphoryl dichlorides |
Non-Patent Citations (1)
| Title |
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| "An 2H N.M.R. study of solid methyl parathione-d6 and parathione-d6 Molecular conformation and selective flexibility";Eva Meirovitch et al.;《Molecular Physics》;20060823;第56卷(第5期);第1129-1143页 * |
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