CN112028938A - Stable isotope labeled chlorpyrifos-d 10 and synthesis method thereof - Google Patents
Stable isotope labeled chlorpyrifos-d 10 and synthesis method thereof Download PDFInfo
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- SBPBAQFWLVIOKP-MWUKXHIBSA-N bis(1,1,2,2,2-pentadeuterioethoxy)-sulfanylidene-(3,5,6-trichloropyridin-2-yl)oxy-$l^{5}-phosphane Chemical compound [2H]C([2H])([2H])C([2H])([2H])OP(=S)(OC([2H])([2H])C([2H])([2H])[2H])OC1=NC(Cl)=C(Cl)C=C1Cl SBPBAQFWLVIOKP-MWUKXHIBSA-N 0.000 title claims abstract description 27
- 238000001308 synthesis method Methods 0.000 title claims abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 20
- KMJJJTCKNZYTEY-UHFFFAOYSA-N chloro-diethoxy-sulfanylidene-$l^{5}-phosphane Chemical compound CCOP(Cl)(=S)OCC KMJJJTCKNZYTEY-UHFFFAOYSA-N 0.000 claims abstract description 18
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims abstract description 13
- 230000008569 process Effects 0.000 claims abstract description 11
- LFQSCWFLJHTTHZ-WFVSFCRTSA-N deuteriooxyethane Chemical compound [2H]OCC LFQSCWFLJHTTHZ-WFVSFCRTSA-N 0.000 claims abstract description 10
- PKUWKAXTAVNIJR-UHFFFAOYSA-N O,O-diethyl hydrogen thiophosphate Chemical compound CCOP(O)(=S)OCC PKUWKAXTAVNIJR-UHFFFAOYSA-N 0.000 claims abstract description 9
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 7
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 7
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 7
- CYQAYERJWZKYML-UHFFFAOYSA-N phosphorus pentasulfide Chemical compound S1P(S2)(=S)SP3(=S)SP1(=S)SP2(=S)S3 CYQAYERJWZKYML-UHFFFAOYSA-N 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 25
- 239000000047 product Substances 0.000 claims description 18
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 238000001816 cooling Methods 0.000 claims description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 claims description 6
- DXEYVFFFVOFVOK-UHFFFAOYSA-N sodium;3,5,6-trichloro-1h-pyridin-2-one Chemical compound [Na].ClC=1C=C(Cl)C(=O)NC=1Cl DXEYVFFFVOFVOK-UHFFFAOYSA-N 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000012044 organic layer Substances 0.000 claims description 4
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 3
- 239000004327 boric acid Substances 0.000 claims description 3
- 238000004440 column chromatography Methods 0.000 claims description 3
- 238000006482 condensation reaction Methods 0.000 claims description 3
- 238000004321 preservation Methods 0.000 claims description 3
- 239000008213 purified water Substances 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 claims description 3
- 239000012467 final product Substances 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 238000001953 recrystallisation Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims 1
- 239000005944 Chlorpyrifos Substances 0.000 abstract description 24
- SBPBAQFWLVIOKP-UHFFFAOYSA-N chlorpyrifos Chemical compound CCOP(=S)(OCC)OC1=NC(Cl)=C(Cl)C=C1Cl SBPBAQFWLVIOKP-UHFFFAOYSA-N 0.000 abstract description 23
- 239000000126 substance Substances 0.000 abstract description 5
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 4
- 238000001948 isotopic labelling Methods 0.000 abstract description 3
- 239000011734 sodium Substances 0.000 abstract description 3
- 229910052708 sodium Inorganic materials 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 2
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 6
- 230000000694 effects Effects 0.000 description 5
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- 238000010189 synthetic method Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- 241000607479 Yersinia pestis Species 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 102000003914 Cholinesterases Human genes 0.000 description 2
- 108090000322 Cholinesterases Proteins 0.000 description 2
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 230000000895 acaricidal effect Effects 0.000 description 2
- 239000000642 acaricide Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- -1 chlorpyrifos compound Chemical class 0.000 description 2
- 229940048961 cholinesterase Drugs 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 238000011161 development Methods 0.000 description 2
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- 238000004750 isotope dilution mass spectroscopy Methods 0.000 description 2
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- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
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- 238000001228 spectrum Methods 0.000 description 2
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- 241000238876 Acari Species 0.000 description 1
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- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 208000003643 Callosities Diseases 0.000 description 1
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- 229920000742 Cotton Polymers 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
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- 241000219146 Gossypium Species 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 0.000 description 1
- 240000003553 Leptospermum scoparium Species 0.000 description 1
- 208000035967 Long Term Adverse Effects Diseases 0.000 description 1
- 235000015459 Lycium barbarum Nutrition 0.000 description 1
- 244000141359 Malus pumila Species 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 241000220324 Pyrus Species 0.000 description 1
- 206010070863 Toxicity to various agents Diseases 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 229940022698 acetylcholinesterase Drugs 0.000 description 1
- 235000021016 apples Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
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- 239000013078 crystal Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000004431 deuterium atom Chemical group 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
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- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000005183 environmental health Effects 0.000 description 1
- 238000003958 fumigation Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
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- 238000005259 measurement Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000003986 organophosphate insecticide Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 235000021017 pears Nutrition 0.000 description 1
- 239000000447 pesticide residue Substances 0.000 description 1
- 230000029553 photosynthesis Effects 0.000 description 1
- 238000010672 photosynthesis Methods 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000007430 reference method Methods 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 235000013311 vegetables Nutrition 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
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
-
- 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
- C07B59/002—Heterocyclic compounds
-
- 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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a stable isotope labeled chlorpyrifos-d 10 and a synthesis method thereof, wherein stable isotope labeled ethanol-d 10 is used as a stable isotope labeled source, and is firstly reacted with phosphorus pentasulfide to obtain stable isotope labeled o, o-diethyl thiophosphate, and then the stable isotope labeled o, o-diethyl thiophosphoryl chloride is obtained by chlorination reaction with phosphorus pentachloride, and then the stable isotope labeled o, o-diethyl thiophosphoryl chloride is condensed with 3,5, 6-trichloro-2-sodium pyridinol to obtain a stable isotope labeled chlorpyrifos-d 10 product. The stable isotope labeling raw material used in the invention is ethanol-d 10, the source is easy to obtain and the price is low, the synthesis process is simple and easy to operate, the product is simple and convenient to separate and purify, the chemical purity and the isotope abundance of the obtained product can reach more than 98 percent, and the related requirements of the product as a standard reagent for quantitatively detecting the content of chlorpyrifos are met.
Description
Technical Field
The invention relates to an isotope labeled compound and a synthetic method thereof, in particular to a stable isotope labeled chlorpyrifos-d 10 and a synthetic method thereof.
Background
Chlorpyrifos, also known as chlorpyrifos, is white crystal, has slight mercaptan smell, and is an efficient, broad-spectrum and low-residue organophosphorus insecticide and acaricide. Chlorpyrifos is an acetylcholinesterase inhibitor, belongs to thiophosphate insecticides, has the effects of contact poisoning, stomach poisoning and fumigation, has strong knockdown force and has a certain osmosis effect. It can inhibit the activity of acetylcholinesterase or cholinesterase in nerve to destroy normal nerve impulse conduction, and cause toxic symptoms. Chlorpyrifos is a broad-spectrum insecticide and acaricide, has high volatility in soil, and is suitable for controlling pests and mites on various crops such as oranges, cotton, corns, apples, pears, rice, peanuts, soybeans, wheat, tea trees and the like. Chlorpyrifos can inhibit cholinesterase activity and block photosynthesis of plants, so that the chlorpyrifos is a pesticide and a herbicide. Chlorpyrifos belongs to a medium-toxicity pesticide, can well control overground and underground pests of various crops, has good control effect on resistant pests, is an ideal variety for replacing high-toxicity organophosphorus insecticides, and has few products capable of replacing all advantages of the organophosphorus insecticides. However, the chlorpyrifos is quite stable in soil, and hardly migrates or volatilizes after being firmly combined with soil particles, and plants are unlikely to absorb the chlorpyrifos from the soil through root systems, so that the chlorpyrifos applied to leaves or fruits mainly volatilizes into the atmosphere, and the drug residue period reaches 10-14 days. It has a long period of efficacy and is extremely toxic to aquatic organisms, possibly resulting in long-term adverse effects on the aquatic environment, so that the use of chlorpyrifos in vegetables is banned in many countries. Therefore, the application range and safety of chlorpyrifos are still to be enhanced.
The stable isotope labeled compound plays an important role in basic science, such as the fields of chemistry, materials, medicine, biological engineering and the like, and the fields of clinical tests and the like. Many researchers have tried to search for stable isotope-labeled compounds for the mechanism of action, circulatory metabolism, etc. of drugs. Meanwhile, the stable isotope dilution mass spectrometry is combined with the LC/MS coupling technology, so that the chromatography/isotope dilution mass spectrometry technology is known as a reference method for measuring trace and trace organic matters. The successful development of the stable isotope labeled chlorpyrifos compound provides a standard reagent for quantitative application of pesticides such as chlorpyrifos in the aspects of pesticide residue, water body soil environment and other content, improves the pesticide products in China, has a detection technology system of environmental safety, meets the requirements of pesticide application and environmental health development in China, and provides important technical support.
The existing common method for synthesizing chlorpyrifos is mostly prepared by condensation reaction of o, o-diethyl thiophosphoryl chloride and 3,5, 6-trichloro-2-pyridine sodium alcoholate under the alkaline condition, and is relatively complex. Therefore, a synthetic method which is simple in operation, high in yield and environment-friendly in process is needed to be found for stable isotope labeling of chlorpyrifos.
Disclosure of Invention
The invention aims to solve the technical problem of providing a stable isotope labeled chlorpyrifos-d 10 and a synthetic method thereof, which can be used as a standard reagent for quantitatively detecting the chlorpyrifos; and the preparation process is simple, the product is easy to separate and purify, and the obtained product has high chemical purity and deuterated purity.
The technical scheme adopted by the invention for solving the technical problems is to provide a method for synthesizing stable isotope labeled chlorpyrifos-d 10, which comprises the following steps: s1: reacting phosphorus pentachloride with ethanol-d 10 to obtain o, o-diethyl thiophosphate; s2: performing chlorination reaction on o, o-diethyl thiophosphate and phosphorus pentachloride to prepare o, o-diethyl thiophosphoryl chloride; s3: carrying out condensation reaction on o, o-diethyl thiophosphoryl chloride and 3,5, 6-trichloro-2-pyridine sodium alcoholate under an alkaline condition to obtain a crude chlorpyrifos-d 10 product marked by stable isotopes; s4: and (3) carrying out recrystallization operation on the crude chlorpyrifos-d 10 product by using absolute ethyl alcohol to obtain a stable isotope labeled chlorpyrifos-d 10 final product.
Further, the step S1 process is as follows: adding 0.9-1.2 parts by weight of phosphorus pentasulfide into a reaction container, dropwise adding 1.0-1.2 parts by weight of ethanol-d 10 at 80-90 ℃, controlling the dropwise adding time to be 1-2 hours, after dropwise adding, keeping the temperature at 80-90 ℃, stirring for 1-3 hours, and cooling to 40-50 ℃ for later use.
Further, the step S2 process is as follows: adding 2.0-4.0 parts by weight of phosphorus pentachloride into the o, o-diethyl thiophosphate reaction solution prepared in the step S1 in batches for chlorination reaction; after the reaction is finished, cooling the solution to room temperature; and (4) separating and purifying by column chromatography to obtain a colorless liquid of o, o-diethyl thiophosphoryl chloride.
Further, in the adding process of the step S2, the reaction temperature is controlled to be 40-50 ℃, and 2.0-3.0 parts of phosphorus pentachloride is added for chlorination reaction.
Further, the step S3 process is as follows: adding 0.9-1.2 parts by weight of 3,5, 6-trichloro-2-pyridinol sodium into a reaction container, adding 5-6 parts by weight of purified water, adding 0.04-0.06 part by weight of boric acid, 0.02-0.03 part by weight of sodium chloride, 0.02-0.04 part by weight of sodium hydroxide, 0.002-0.004 part by weight of benzyltriethylammonium chloride and 0.001-0.003 part by weight of 4-dimethylaminopyridine, adjusting the temperature to 40-50 ℃, dropwise adding 0.5-1.0 part by weight of o, o-diethylthiophosphoryl chloride, and reacting for 1-3 hours at 40-50 ℃ after dropwise adding; after the reaction is finished, cooling, and concentrating under reduced pressure to obtain a crude chlorpyrifos-d 10 product.
Further, in step S3, 0.5 to 1.0 part of o, o-diethylthiophosphoryl chloride is dissolved in 3 to 5 parts of dichloromethane, and then dropwise added.
The invention also provides a stable isotope labeled chlorpyrifos product, which is obtained by the synthesis method and has the following molecular structure:
the invention has the following beneficial effects: according to the stable isotope labeled chlorpyrifos-d 10 and the synthesis method thereof, ethanol-d 10 with isotope abundance of more than 98 atom% is used as an isotope labeled source, chlorpyrifos-d 10 is synthesized through simple three-step reaction, deuterium atoms cannot fall off in the reaction process of each step, and the utilization rate of the stable isotope atoms is high; the synthetic process is simple, the product is easy to separate and purify, the chemical purity and the isotopic abundance of the obtained product both reach more than 98 percent, and the requirement of the product as a standard reagent for quantitatively detecting the chlorpyrifos is met; high use value and good economical efficiency.
Drawings
FIG. 1 is a gas chromatogram of chlorpyrifos-d 10 obtained in example 1 of the present invention.
FIG. 2 is a mass spectrum of chlorpyrifos-d 10 obtained in example 1 of the present invention.
Detailed Description
The invention is further described in connection with the following figures and examples, which should not be construed as limiting the invention.
The invention provides a method for simply and efficiently preparing a stable isotope labeled chlorpyrifos-d 10 compound by using a 2H isotope labeling technology, using ethanol-d 10 as a stable deuterium band source and preparing stable isotope labeled o, o-diethyl thiophosphoryl chloride through a one-pot reaction. The synthesis method of the chlorpyrifos marked by the stable isotope comprises the following steps:
s1: reacting phosphorus pentachloride with ethanol-d 10 to obtain o, o-diethyl thiophosphate marked by stable isotope;
the molecular structure is as follows:
s2: reacting o, o-diethyl thiophosphate with phosphorus pentachloride to obtain stable isotope labeled o, o-diethyl thiophosphoryl chloride;
the molecular structure is as follows:
s3: reacting 3,5, 6-trichloro-2-pyridinol sodium with o, o-diethyl thiophosphoryl chloride labeled by stable isotopes, and recrystallizing a crude product in absolute ethyl alcohol to obtain chlorpyrifos-d 10 white solid labeled by stable isotopes;
the solvent adopted in the steps can be dry anhydrous solvent; the stable isotope labeled chlorpyrifos
The molecular structure of d10 is:
example 1
The molecular structure of the stable isotope labeled chlorpyrifos is as follows:
the preparation method comprises the following synthetic steps:
s1, adding 10.5g of phosphorus pentachloride into a reaction container, dropwise adding 10g of stable isotope labeled ethanol-d 10 at the temperature of 80-90 ℃, controlling the dropwise adding time within 1-3 hours, and leading the late-stage yield to be low due to the fact that the dropwise adding is too fast and the reaction is relatively serious in heat release. After the dropwise addition is finished, the reaction is carried out for 1-3 hours in a heat preservation mode, the reaction can be promoted to be completely carried out at the temperature through heat preservation, the reaction liquid is strong in acidity due to the fact that the temperature is too low, and the consumption of raw materials in the next step is large; and then stopping heating the reaction container, cooling to 40-50 ℃, and directly using the reaction solution for the next synthesis without further purification.
S2, adding 25g of phosphorus pentachloride solid in batches into the reaction container in the previous step, wherein the phosphorus pentachloride is solid and cannot be added all at once, and the reaction has too much heat release and is easy to wash; and after the addition is finished, reacting for 2 hours at the temperature of 40-50 ℃, cooling to room temperature after the reaction is finished, and separating and purifying by column chromatography to obtain the o, o-diethyl thiophosphoryl chloride.
S3, adding 7.3g of 3,5, 6-trichloro-2-pyridinol sodium into a reaction container, adding 40ml of water, adding 0.35g of boric acid, 0.16g of sodium chloride, 0.19g of sodium hydroxide, 0.034g of benzyltriethylammonium chloride and 0.02g of 4-dimethylaminopyridine, dropwise adding 5.6g of stable isotope labeled o, o-diethylthiophosphoryl chloride (dissolved in 25ml of dichloromethane), reacting at 40-50 ℃ for 1-3 hours after dropwise adding is completed, stopping stirring, separating an organic layer, washing the organic layer with 10ml of purified water, and concentrating the organic layer under reduced pressure to obtain a white solid crude product of chlorpyrifos. And recrystallizing, separating and purifying the crude product by absolute ethyl alcohol to obtain the white solid of the chlorpyrifos-d 10 marked by the stable isotope. 8g of chlorpyrifos-d 10 obtained after purification is white powder solid, and the chemical purity and the isotopic abundance can both reach more than 98 percent.
The nuclear magnetic resonance hydrogen spectrum of the product obtained in the example was detected by a Bruke-400M nuclear magnetic resonance instrument with (CD3)2SO as to be a solvent. H NMR (CD3)2SO) 1.2 methyl hydrogens and 4.0 methylene hydrogens were replaced with deuterium, and no peak was observed in the spectrum, thus confirming that the product was chlorpyrifos-d 10, an isotope-stable marker.
Meanwhile, the product sample obtained in this example is dissolved in methanol (1 ppm) for purity and MS measurement, and the spectrogram is shown in FIG. 1 and FIG. 2. In spectrogram 1, no obvious impurity peak is detected, and the chemical purity of the chlorpyrifos-d 10 product can reach more than 99%. In spectrogram 2, MS data shows LC-MS M/z 324[ M-2CD3], so that the MS data are correct (the molecular weight of chlorpyrifos-d 10 is 360.6).
Although the present invention has been described with respect to the preferred embodiments, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (7)
1. A method for synthesizing stable isotope labeled chlorpyrifos-d 10 is characterized by comprising the following steps:
s1: phosphorus pentasulfide is used for reacting with ethanol-d 10 to prepare O, O-diethyl thiophosphate marked by stable isotope;
s2: performing chlorination reaction on o, o-diethyl thiophosphate and phosphorus pentachloride to obtain stable isotope labeled o, o-diethyl thiophosphoryl chloride;
s3: carrying out condensation reaction on 3,5, 6-trichloro-2-pyridinol sodium and o, o-diethyl thiophosphoryl chloride marked by stable isotopes to obtain a crude chlorpyrifos-d 10 product marked by the stable isotopes;
s4: and (3) carrying out recrystallization operation on the crude chlorpyrifos-d 10 product by using absolute ethyl alcohol to obtain a stable isotope labeled chlorpyrifos-d 10 final product.
2. The method of synthesis according to claim 1, characterized in that: the step S1 process is as follows: adding 0.9-1.2 parts by weight of phosphorus pentasulfide into a reaction container, dropwise adding 1.0-1.2 parts by weight of ethanol-d 10 at the temperature of 80-90 ℃, controlling the dropwise adding time within 1-2 hours, after dropwise adding, carrying out heat preservation reaction at the temperature of 80-90 ℃ for 1-3 hours, and then cooling to 40-50 ℃ for later use.
3. The method of synthesis according to claim 1, characterized in that: the step S2 process is as follows: adding 2.0-4.0 parts by weight of phosphorus pentachloride into the o, o-diethyl thiophosphate reaction solution prepared in the step S1 in batches for chlorination reaction; after the reaction is finished, cooling the solution to room temperature; and (4) separating and purifying by column chromatography to obtain a colorless liquid of o, o-diethyl thiophosphoryl chloride.
4. The method of synthesis according to claim 3, characterized in that: and in the adding process of the step S2, the reaction temperature is controlled to be 40-50 ℃, and 2.0-3.0 parts of phosphorus pentachloride is added for chlorination reaction.
5. The method of synthesis according to claim 1, characterized in that: the step S3 process is as follows: adding 0.9-1.2 parts by weight of 3,5, 6-trichloro-2-pyridinol sodium into a reaction container, adding 5-6 parts by weight of purified water, adding 0.04-0.06 part by weight of boric acid, adding 0.02-0.03 part by weight of sodium chloride, 0.02-0.04 part by weight of sodium hydroxide, 0.002-0.004 part by weight of benzyltriethylammonium chloride and 0.001-0.003 part by weight of 4-dimethylaminopyridine, adjusting the temperature to 40-50 ℃, dropwise adding 0.5-1.0 part by weight of o, o-diethylthiophosphoryl chloride at the temperature, and reacting for 1-3 hours at 40-50 ℃ after dropwise adding; after the reaction is finished, an organic layer is separated, and the mixture is concentrated under reduced pressure to obtain a crude chlorpyrifos-d 10 product.
6. The method of synthesis according to claim 5, characterized in that: in the step S3, 0.5-1.0 part of o, o-diethyl thiophosphoryl chloride is dissolved in 3-5 parts of dichloromethane, and then dropwise added.
7. A stable isotope labelled chlorpyrifos-d 10, having the following molecular structure, prepared by the synthesis method according to any one of claims 1 to 6:
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