CN110016050A - A kind of stable isotope labeling chlopyrifos and its derivative and synthesis preparation method - Google Patents
A kind of stable isotope labeling chlopyrifos and its derivative and synthesis preparation method Download PDFInfo
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- CN110016050A CN110016050A CN201910277096.9A CN201910277096A CN110016050A CN 110016050 A CN110016050 A CN 110016050A CN 201910277096 A CN201910277096 A CN 201910277096A CN 110016050 A CN110016050 A CN 110016050A
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Abstract
The invention discloses stable isotope labeling chlopyrifos and its derivative and synthesis preparation method, utilize methodology of organic synthesis, using phosphorus thiochloride as raw material, successively with stable isotope labeling 3,5,6- trichloropyridine -2- sodium alkoxides, stable isotope labeling short chain alcohol react to obtain stable isotope labeling chlopyrifos and its derivative；Stable isotope labeling chlopyrifos prepared by the present invention and its derivative are after simple separation purifies, chemical purity is up to 99% or more, 99% or more isotope abundance, can be applied to the fields such as biological metabolism, food safety, environmental monitoring, and the external product that compares has advantage high-quality, at low cost.
Description
Technical field
The present invention relates to a kind of compound of stable isotope labeling and its synthesis preparation method more particularly to a kind of stabilizations
Isotope labelling chlopyrifos and its derivative and synthesis preparation method.
Background technique
Chlopyrifos, chemical name O, O- diethyl-O (3,5,6- trichloro-2-pyridyl) thiophosphate, international name
Chlorprifos.It is efficient one kind that Dow company, the U.S. develops in nineteen sixty-five, low toxicity, wide spectrum, low-residual and low drug resistance
Organic phosphorus insecticidal/acaricidal agent, have tag, stomach toxicity and fumigation action, rice, wheat, corn, cotton, sweet can be effectively prevented
Snout moth's larva, leaf folder, mythimna separata, scale insect, aphid, leafhopper and the harmful mite of sugarcane, tealeaves, fruit tree, flowers and herding etc. etc. are over one hundred
Kind pest.The derivative chlorpyrifos-methyl of chlopyrifos, propyl chlopyrifos etc. are also applied in pesticide.
But chlopyrifos is volatile, and solubility in water is smaller, is easily adsorbed by the particulate matter in soil, drop in the soil
Long half time is solved up to 9.8~63d, degradation speed is slower.Plant is such as: the chlopyrifos in soil, Er Qiesui can be absorbed in Xiaoqinling Nature Reserve
The increasing of the dead tick residual quantity of soil poisoning, the content of Xiaoqinling Nature Reserve plant tissue Chlorpyrifos also increase with it, may be to human body
Health causes potential danger.In addition, chlopyrifos is the inhibitor of acetylcholinesterase, even if low dosage may also cause human body
Injury, may will affect central nervous system, cardiovascular system, respiratory system.Children are higher than adult to the sensibility of chlopyrifos,
It is more vulnerable to endanger.The derivative of chlopyrifos also has similar injury to human body.
Therefore, very necessary to the detection of the dead tick of sitotoxismus and monitoring.But complicated matrix effect in food, needs to use
Stable isotope internal standard method is accurately detected.Meanwhile the metabolism and degradation of biological metabolism field chlopyrifos and its derivative are ground
Study carefully chlopyrifos and its derivative product for being also badly in need of stable isotope labeling.
The synthesis document report of domestic and international rarely seen stable isotope labeling chlopyrifos and its derivative at present, natural poisons with poison
The synthesis document of tick is mostly with phosphorus thiochloride and excessive ethanol synthesis preparation O, O- diethyl sulfo-phosphoryl chloride, then again in phase
Transfer catalyst acts on lower and tri- Chloro-2-Pyridyle alcohol of 3,5,6- or sodium salt two phase reaction prepares chlopyrifos.Natural method synthesis poison
Dead tick needs to prepare in two steps, and the first step prepares O, and ethyl alcohol consumption is big when O- diethyl sulfo-phosphoryl chloride, is easy to generate by-product
Object O, O, O- triethyl group thiophosphate, product need rectification and purification energy consumption high.Second step is reacted in water phase, alkalinity, phase transfer
Chlopyrifos can be just prepared in long-time pyroreaction under the conditions of catalyst etc., be easy the generation of by-product thiotep.It is this anti-
Route and its reaction condition is answered to be difficult to apply to the synthesis of stable isotope labeling chlopyrifos and its derivative, excessive ethyl alcohol is thrown
Enter and subsequent water phase, soda acid and pyroreaction had both reduced the Atom economy that isotope utilizes, is also easy to isotope abundance
It causes to dilute, cannot get the stable isotope labeling chlopyrifos and its derivative produce that abundance is high, purity is good, Atom economy is high
Product.
Summary of the invention
It is an object of the invention to provide a kind of stable isotope labeling chlopyrifos and its derivative and synthesis preparation method, former
Expect cheap and easy to get, reaction process is simple, and stable isotope atom utilization is high, and no waste water generates, and obtained target product tool
There are very high chemical purity and isotope abundance.
The purpose of the present invention can be achieved through the following technical solutions: a kind of stable isotope labeling chlopyrifos and its spreading out
Biology, structural formula are as follows:
R is methyl, ethyl, propyl, isopropyl or butyl, and a, b, c, d, e, f, g, at least one in R group are stood alone as13C、
D、15N or18O isotope labelling.
Further, it is at a18O label.
Further, it is at described b, c, e or f13C flag.
Further, at the d or R group is13One or two kinds of label of C flag, D.
Further, it is at the g15N label.
The present invention also provides a kind of aforementioned stable isotope labelling chlopyrifos and its synthetic methods of derivative, wherein packet
Include following steps: using phosphorus thiochloride as raw material, successively with 3,5,6- trichloropyridine -2- sodium alkoxide of stable isotope labeling, stabilization
Isotope labelling short chain alcohol is reacted under liquid phase alkaline condition to be obtained.
Further, the phosphorus thiochloride, stable isotope labeling 3,5,6- trichloropyridine -2- sodium alkoxide and stablize same position
The molar ratio of element label short chain alcohol is 1:1:1~1:5:5, and reaction temperature is -50~200 DEG C.
Further, the phosphorus thiochloride, stable isotope labeling 3,5,6- trichloropyridine -2- sodium alkoxide and stablize same position
The molar ratio of element label short chain alcohol is 1:1:1~1:2:3, and reaction temperature is -20~80 DEG C.
Further, the liquid phase is one of toluene, ethylbenzene, dimethylbenzene and isopropylbenzene or combinations thereof.
Further, added with tert-butylamine, n-butylamine and one kind of isopropylamine or combinations thereof in the liquid phase.
Compared with prior art, the invention has the following beneficial effects: the present invention using phosphorus thiochloride as raw material, successively and surely
Determine isotope labelling 3,5,6- trichloropyridine -2- sodium alkoxide, stable isotope labeling short chain alcohol is reacted under liquid phase alkaline condition
Obtain stable isotope labeling chlopyrifos and its derivative.Raw material is cheap and easy to get, and reaction process is simple, mild condition, high income,
Stable isotope atom utilization is high, and no waste water generates, and is the synthesis for being suitble to stable isotope labeling chlopyrifos and its derivative
Method, and stable isotope labeling chlopyrifos and its derivative are succeeded in developing, will for biological metabolism field chlopyrifos and its
Derivatives metabolism research provides metabolism standard items, while also will provide mark for more accurate quantitative detection chlopyrifos and its derivative
Quasi- reagent, to effectively provide service for biological metabolism field, food safety, environmental monitoring field.
Specific embodiment
Below with reference to embodiment, the invention will be further described.
A kind of stable isotope labeling chlopyrifos provided by the invention and its derivative, structural formula are as follows:
R is methyl, ethyl, propyl, isopropyl or butyl, and a, b, c, d, e, f, g, at least one in R group are stood alone as13C、
D、15N or18O isotope labelling.Specifically, in above compound everywhere in the labelled atom of atom its stable isotope taken
The label in generation is as follows:
It is at a18O label or non-marked；
It is at the b13C flag or non-marked；
It is at the c13C flag or non-marked；
It is at the d13C flag, one or two kinds of label of D (deuterium) or non-marked；
It is at the e13C flag or non-marked；
It is at the f13C flag or non-marked；
It is at the g15N label or non-marked；
The R group is13C flag, one or two kinds of label of D (deuterium) or non-marked.
Embodiment 1
A kind of stable isotope labeling chlopyrifos-D10Preparation method, method includes the following steps:
17.0g phosphorus thiochloride is added in 250mL three-necked flask, toluene 100mL is added at -5 DEG C, is added portionwise under stirring
3,5,6- trichloropyridine -2- sodium alkoxide 22.1g, after adding, 0 DEG C of temperature control is reacted 1 hour, adds ethyl alcohol-D610.4g, isopropyl
Amine 11.8g heats up 40 DEG C and reacts 2 hours, filters, and obtains 34.8g chlopyrifos-D after removing solvent10Solid, yield 96.7%, GC
Detection, purity 99.5%；Mass Spectrometer Method, abundance 99.6atom%D.
Embodiment 2
A kind of stable isotope labeling chlorpyrifos-methyl-D6Preparation method, method includes the following steps:
8.5g phosphorus thiochloride is added in 250mL three-necked flask, dimethylbenzene 70mL is added at -15 DEG C, adds in batches under stirring
Enter 3,5,6- trichloropyridine -2- sodium alkoxide 12.1g, after adding, 0 DEG C of temperature control is reacted 1 hour, adds methanol-D47.5g, uncle
Propylamine 7.8g heats up 60 DEG C and reacts 1 hour, filters, and obtains 15.0g chlorpyrifos-methyl-D after removing solvent6Solid, yield
91.5%, GC detection, purity 99.5%；Mass Spectrometer Method, abundance 99.7atom%D.
Embodiment 3
A kind of stable isotope labeling chlopyrifos-13C5Preparation method, method includes the following steps:
17.0g phosphorus thiochloride is added in 250mL three-necked flask, ethylbenzene 80mL is added at -20 DEG C, is added portionwise under stirring
3,5,6- trichloropyridine -2- sodium alkoxide -13C522.1g, after adding, 0 DEG C of temperature control is reacted 1 hour, adds ethyl alcohol 12.4g, different
Propylamine 11.8g heats up 60 DEG C and reacts 1.5 hours, filters, and obtains 34.9g chlopyrifos-after removing solvent13C5Solid, yield
97.7%, GC detection, purity 99.5%；Mass Spectrometer Method, abundance 99.6atom%13C。
Embodiment 4
A kind of stable isotope labeling chlopyrifos-13C9D11 15N18O3Preparation method, method includes the following steps:
8.5g phosphorus thiochloride is added in 250mL three-necked flask, isopropylbenzene 100mL is added at -10 DEG C, adds in batches under stirring
Enter 3,5,6- trichloropyridine -2- sodium alkoxide -13C5D15N18O 11.6g, after adding, 0 DEG C of temperature control is reacted 1.5 hours, adds second
Alcohol-13C2D6 18O 11.5g, tertiary propylamine 8.8g, heat up 70 DEG C and react 1.5 hours, filter, and obtain 17.9g after removing solvent and poison with poison
Tick-13C9D11 15N18O3Solid, yield 98.7%, GC detection, purity 99.5%；Mass Spectrometer Method, abundance 99.6atom%13CD15N18O。
Embodiment 5
A kind of stable isotope labeling propyl chlopyrifos-13C5Preparation method, method includes the following steps:
The phosphorus thiochloride and 3,5,6- trichloropyridine -2- sodium alkoxide-for being 1:1.1 by molar ratio13C5It is mixed at 0 DEG C, reaction
After 0.5 hour, propyl alcohol, the isopropylamine of 2.1 equivalents are added, 80 DEG C of temperature control, reacts 3 hours, obtains propyl chlopyrifos-13C5。
Embodiment 6
A kind of stable isotope labeling isopropyl chlopyrifos-D14Preparation method, method includes the following steps:
The phosphorus thiochloride and 3 for being 1:1.2 by molar ratio, 5,6- trichloropyridine -2- sodium alkoxides are mixed at 5 DEG C, and reaction 2.5 is small
Shi Hou adds isopropanol, the n-butylamine of 2.5 equivalents, 50 DEG C of temperature control, reacts 4 hours, obtain isopropyl chlopyrifos-D14。
Embodiment 7
A kind of stable isotope labeling normal-butyl chlopyrifos-13C8Preparation method, method includes the following steps:
The phosphorus thiochloride and 3 for being 1:1.5 by molar ratio, 5,6- trichloropyridine -2- sodium alkoxides are mixed at -15 DEG C, reaction 1.5
After hour, the n-butanol-of 2.1 equivalents is added13C4, tert-butylamine, 40 DEG C of temperature control, react 5 hours, obtain normal-butyl chlopyrifos-13C8。
Embodiment 8
A kind of stable isotope labeling chlorpyrifos-methyl-13C7D7 15N18O3Preparation method, method includes the following steps:
The phosphorus thiochloride and 3,5,6- trichloropyridine -2- sodium alkoxide-for being 1:1.2 by molar ratio13C5D15N18O-5 DEG C of mixing
Afterwards, it reacts 1 hour, adds the methanol-of 2.3 equivalents13CD4 18O, isopropylamine, reacts 3 hours by 40 DEG C of temperature control, obtains methyl poison
Dead tick-13C7D7 15N18O3。
The present invention utilize methodology of organic synthesis, using phosphorus thiochloride as raw material, successively with stable isotope labeling 3,5,6- tri-
Chloropyridine -2- sodium alkoxide, stable isotope labeling short chain alcohol react to obtain stable isotope labeling chlopyrifos and its derivative；This
The stable isotope labeling chlopyrifos for inventing preparation and its derivative are after simple separation purifies, chemical purity and isotope abundance
Height can be applied to the fields such as biological metabolism, food safety, environmental monitoring, and the external product that compares has high-quality, at low cost
Advantage.Specific advantage is as follows: 1) present invention uses synthetic method, and raw material is cheap and easy to get, and reaction process is simple, mild condition, receives
Rate is high, and stable isotope atom utilization is high, and no waste water generates.2) the easily separated purification of product of the present invention, product chemical purity exist
99% or more, isotope abundance is 99% or more.3) present invention has good economy and use value.
Although the present invention is disclosed as above with preferred embodiment, however, it is not to limit the invention, any this field skill
Art personnel, without departing from the spirit and scope of the present invention, when can make a little modification and perfect therefore of the invention protection model
It encloses to work as and subject to the definition of the claims.
Claims (10)
1. a kind of stable isotope labeling chlopyrifos and its derivative, which is characterized in that structural formula is as follows:
R is methyl, ethyl, propyl, isopropyl or butyl, and a, b, c, d, e, f, g, at least one in R group are stood alone as13C、D、15N
Or18O isotope labelling.
2. stable isotope labeling chlopyrifos as described in claim 1 and its derivative, which is characterized in that be at a18O
Label.
3. stable isotope labeling chlopyrifos as described in claim 1 and its derivative, which is characterized in that described b, c, e or f
Place is13C flag.
4. stable isotope labeling chlopyrifos as described in claim 1 and its derivative, which is characterized in that at the d or R base
It rolls into a ball and is13One or two kinds of label of C flag, D.
5. stable isotope labeling chlopyrifos as described in claim 1 and its derivative, which is characterized in that be at the g15N
Label.
6. the synthetic method of a kind of stable isotope labeling chlopyrifos as claimed in any one of claims 1 to 5 and its derivative,
Characterized by comprising the following steps:
Using phosphorus thiochloride as raw material, successively with 3,5,6- trichloropyridine -2- sodium alkoxide of stable isotope labeling, stable isotope mark
Note short chain alcohol is reacted under liquid phase alkaline condition to be obtained.
7. synthetic method according to claim 6, it is characterised in that: the phosphorus thiochloride, stable isotope labeling 3,5,
The molar ratio of 6- trichloropyridine -2- sodium alkoxide and stable isotope labeling short chain alcohol is 1:1:1~1:5:5, and reaction temperature is -50
~200 DEG C.
8. synthetic method according to claim 7, it is characterised in that: the phosphorus thiochloride, stable isotope labeling 3,5,
The molar ratio of 6- trichloropyridine -2- sodium alkoxide and stable isotope labeling short chain alcohol is 1:1:1~1:2:3, and reaction temperature is -20
~80 DEG C.
9. synthetic method according to claim 6, it is characterised in that: the liquid phase is toluene, ethylbenzene, dimethylbenzene and isopropyl
One of benzene or combinations thereof.
10. synthetic method according to claim 9, it is characterised in that: in the liquid phase added with tert-butylamine, n-butylamine and
One kind of isopropylamine or combinations thereof.
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| CN108341839A (en) * | 2018-01-10 | 2018-07-31 | 浙江大学 | A kind of insecticide chlorpyrifos and its synthetic method of the label of radioactive isotope carbon -14 |
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