CN112778222B - Stable isotope labeled paclobutrazol- 15 N 3 And method for synthesizing the same - Google Patents
Stable isotope labeled paclobutrazol- 15 N 3 And method for synthesizing the same Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 15
- 230000002194 synthesizing effect Effects 0.000 title description 4
- RMOGWMIKYWRTKW-UONOGXRCSA-N (S,S)-paclobutrazol Chemical compound C([C@@H]([C@@H](O)C(C)(C)C)N1N=CN=C1)C1=CC=C(Cl)C=C1 RMOGWMIKYWRTKW-UONOGXRCSA-N 0.000 claims abstract description 20
- 239000005985 Paclobutrazol Substances 0.000 claims abstract description 19
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 14
- ZGCHATBSUIJLRL-AWQJXPNKSA-N azanylazanium;hydrogen sulfate Chemical compound [15NH2][15NH2].OS(O)(=O)=O ZGCHATBSUIJLRL-AWQJXPNKSA-N 0.000 claims abstract description 9
- ZHNUHDYFZUAESO-VQEHIDDOSA-N azanylformaldehyde Chemical compound [15NH2]C=O ZHNUHDYFZUAESO-VQEHIDDOSA-N 0.000 claims abstract description 8
- 239000007787 solid Substances 0.000 claims abstract description 8
- KQNBRMUBPRGXSL-UHFFFAOYSA-N 1-(bromomethyl)-4-chlorobenzene Chemical compound ClC1=CC=C(CBr)C=C1 KQNBRMUBPRGXSL-UHFFFAOYSA-N 0.000 claims abstract description 7
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims abstract description 7
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims abstract description 7
- 235000019253 formic acid Nutrition 0.000 claims abstract description 7
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 7
- 239000011591 potassium Substances 0.000 claims abstract description 7
- ULSAJQMHTGKPIY-UHFFFAOYSA-N 1-chloro-3,3-dimethylbutan-2-one Chemical compound CC(C)(C)C(=O)CCl ULSAJQMHTGKPIY-UHFFFAOYSA-N 0.000 claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims description 31
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 12
- 238000001308 synthesis method Methods 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 8
- 238000000746 purification Methods 0.000 claims description 7
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 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
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 239000012044 organic layer Substances 0.000 claims description 5
- 150000003852 triazoles Chemical class 0.000 claims description 4
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 239000000706 filtrate Substances 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- NZYOAGBNMCVQIV-UHFFFAOYSA-N sodium;chloro-(4-methylphenyl)sulfonylazanide;trihydrate Chemical compound O.O.O.[Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 NZYOAGBNMCVQIV-UHFFFAOYSA-N 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
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- 230000015572 biosynthetic process Effects 0.000 abstract description 4
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- QWENRTYMTSOGBR-FRSWOAELSA-N (1,2,3-15N3)2H-triazole Chemical compound [15NH]1[15N]=[15N]C=C1 QWENRTYMTSOGBR-FRSWOAELSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
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- 238000002360 preparation method Methods 0.000 description 3
- 244000291564 Allium cepa Species 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-VQEHIDDOSA-N amino(azanyl)methanone Chemical compound [15NH2]C(=O)N XSQUKJJJFZCRTK-VQEHIDDOSA-N 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- XSQUKJJJFZCRTK-SUEIGJEOSA-N bis(azanyl)methanone Chemical compound [15NH2]C([15NH2])=O XSQUKJJJFZCRTK-SUEIGJEOSA-N 0.000 description 2
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- 235000018262 Arachis monticola Nutrition 0.000 description 1
- 235000003092 Artemisia dracunculus Nutrition 0.000 description 1
- 240000001851 Artemisia dracunculus Species 0.000 description 1
- 240000008067 Cucumis sativus Species 0.000 description 1
- 235000010799 Cucumis sativus var sativus Nutrition 0.000 description 1
- 244000000626 Daucus carota Species 0.000 description 1
- 235000002767 Daucus carota Nutrition 0.000 description 1
- 229930191978 Gibberellin Natural products 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 244000088415 Raphanus sativus Species 0.000 description 1
- 235000006140 Raphanus sativus var sativus Nutrition 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 244000273928 Zingiber officinale Species 0.000 description 1
- 235000006886 Zingiber officinale Nutrition 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
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- 238000005516 engineering process Methods 0.000 description 1
- IXORZMNAPKEEDV-UHFFFAOYSA-N gibberellic acid GA3 Natural products OC(=O)C1C2(C3)CC(=C)C3(O)CCC2C2(C=CC3O)C1C3(C)C(=O)O2 IXORZMNAPKEEDV-UHFFFAOYSA-N 0.000 description 1
- 239000003448 gibberellin Substances 0.000 description 1
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- 238000007039 two-step reaction Methods 0.000 description 1
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- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A40/00—Adaptation technologies in agriculture, forestry, livestock or agroalimentary production
- Y02A40/10—Adaptation technologies in agriculture, forestry, livestock or agroalimentary production in agriculture
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention discloses stable isotope labeled paclobutrazol- 15 N 3 And synthetic methods thereof to stabilize isotopes 15 N-labeled hydrazine sulfate- 15 N 2 And urea- 15 N 2 As a source of stable isotope labeling, urea-ion was first used 15 N 2 React with formic acid to obtain isotopic labelled formamide- 15 N, then with hydrazine sulfate- 15 N 2 Further reacting to obtain stable isotope labeled triazole- 15 N 3 Then reacting with chloropinacolone to obtain azolone- 15 N 3 Then reacts with p-chlorobenzyl bromide to obtain chlorzoxazone- 15 N 3 Finally, the stable isotope labeled paclobutrazol-one is obtained by potassium borohydride reduction 15 N 3 A white solid. The marking raw materials used in the invention are easy to obtain and low in price, the synthesis process is simple, the chemical purity and the isotopic abundance of the obtained product reach more than 98 percent, and the obtained product can meet the relevant requirements of serving as a standard reagent for quantitatively detecting the paclobutrazol content.
Description
Technical Field
The invention relates to an isotope labeled compound and a synthetic method thereof, in particular to stable isotope labeled paclobutrazol- 15 N 3 And a method for synthesizing the same.
Background
Paclobutrazol is a triazole plant growth regulator successfully developed in 80 years, and is an inhibitor of endogenous gibberellin synthesis. It has excellent control effect on crop growth, and can delay plant growth, inhibit stalk elongation, raise plant resistance, raise yield and other effects. The product is suitable for being used as (plants) of rice, wheat, peanut, fruit tree, tobacco, rape, soybean, flower, lawn, etc., and has obvious use effect. Paclobutrazol can reduce the cells of roots, leaf sheaths and leaves of rice seedlings and increase the cell layer number of each organ. The tracing analysis shows that the rice seeds, leaves and roots can absorb paclobutrazol. The paclobutrazol absorbed by the leaves is mostly retained in the absorption part and is rarely transported outwards. The low concentration of paclobutrazol can improve the photosynthetic efficiency of the rice seedling leaves; high concentration inhibits photosynthetic efficiency, improves the respiratory intensity of root systems, reduces the respiratory intensity of overground parts, improves the resistance of air holes of the leaves, and reduces the transpiration of the leaves.
The main import countries of vegetables in China, such as European Union, america, korea and the like, have very strict requirements on the residues of paclobutrazol on the vegetables, and the residues of paclobutrazol in the vegetables such as ginger, scallion, onion, carrot, radish, tarragon, cucumber and the like are required to be 'undetected', and the paclobutrazol residues are all the dominant vegetable export varieties in China. If the paclobutrazol is illegally used in the production process of exported vegetables, the problem that pesticide residues exceed standards is easily caused. Therefore, the detection of the residue of paclobutrazol is very important, and further, the detection of paclobutrazol is importantStable isotope labeled paclobutrazol- 15 N 3 The provision of standards of (a) also poses new requirements.
Synthesis of Stable isotope labeled paclobutrazol- 15 N 3 There is little disclosure of (A). Therefore, it is necessary to find a synthetic method with simple operation, high yield and environment-friendly process for labeling paclobutrazol with stable isotope 15 N 3 The synthesis work of (1).
Disclosure of Invention
The technical problem to be solved by the invention is to provide a stable isotope 15 N-labeled paclobutrazol- 15 N 3 The synthesis method can be used as a standard reagent for quantitatively detecting paclobutrazol; and the preparation process is simple, the product is easy to separate and purify, and the obtained product has high chemical purity and isotope abundance.
The technical scheme adopted by the invention for solving the technical problems is to provide stable isotope labeled paclobutrazol- 15 N 3 The synthesis method comprises the following steps: s1: use of urea- 15 N 2 React with formic acid to obtain formamide- 15 N; s2: formamide ion-reaction 15 N and hydrazine sulfate- 15 N 2 Reaction is carried out to obtain the triazole labeled by stable isotope 15 N 3 (ii) a S3: triazole is reacted with 15 N 3 Reacting with chloropinacolone to obtain stable isotope labeled oxazolone- 15 N 3 (ii) a S4: azolone- 15 N 3 Reacts with p-chlorobenzyl bromide to obtain chlorzoxazone- 15 N 3 (ii) a S5: chloro-oxazolone- 15 N 3 Paclobutrazol-one obtained by potassium borohydride reduction 15 N 3 。
Further, the step S1 process is as follows: adding 2.0-2.5 parts of urea-15N2 and 2.0-3.5 parts of formic acid into a reaction vessel according to the parts by weight, and adjusting the temperature to 150-160 ℃; reacting for 3-5 hours at the temperature; after the reaction was completed, the solution was used directly in the next step.
Further, the step S2 process is as follows: according to the parts by weight, the formamide obtained from S1 15 Solution of NHeating to 170-190 ℃, and adding 0.5 part of hydrazine sulfate- 15 N 2 After the solid is added, reacting for 1-2 hours at 170-190 ℃; obtaining stable isotope labeled triazole- 15 N 3 。
Further, the step S3 process is as follows: adding 0.9-1.0 part of triazole- 15 N 3 1.8 to 2.0 portions of chloropinacolone, 2.5 to 3.0 portions of potassium carbonate, 0.01 to 0.02 portion of 18-crown ether-6, 4.0 to 5.0 portions of ethyl acetate, raising the reaction temperature to 60 to 80 ℃, and reacting for 4 to 5 hours at the temperature of 60 to 80 ℃; filtering after the reaction is finished, and purifying the filtrate by a column to obtain the stable isotope labeled oxazolone- 15 N 3
Further, the step S4 process is as follows: according to the weight portion, 0.9-1.0 portion of oxazolone- 15 N 3 7.0 to 8.0 parts of toluene, 1.3 to 1.5 parts of p-chlorobenzyl bromide and 0.04 to 0.06 part of benzyltriethylammonium chloride, raising the reaction temperature to 60 to 80 ℃, dripping 0.6 to 0.7 part of sodium hydroxide aqueous solution with the mass concentration of 40 percent at the temperature of 60 to 80 ℃ at the speed of 0.2 to 0.5mL for 1 second, and reacting for 4 to 5 hours at the temperature of 60 to 80 ℃; adding water for layering after the reaction is finished, concentrating an organic layer and purifying the organic layer by a column to obtain the chlorazol ketone-alpha-ketone labeled by the stable isotope 15 N 3 White solid.
Further, the step S5 process is as follows: according to the weight portion, 0.9 to 1.0 portion of chlorzoxazone- 15 N 3 10 to 15 portions of methanol, 0.3 to 0.5 portion of sodium hydroxide aqueous solution with the mass concentration of 30 percent and 0.1 to 0.2 portion of potassium borohydride, and reacting the reaction solution for 3 to 5 hours at room temperature; obtaining the paclobutrazol-alpha-labeled by stable isotope through column purification 15 N 3 。
The invention also provides a stable isotope labeled paclobutrazol-one prepared by the synthesis method for solving the technical problems 15 N 3 Having a molecular structure as shown below:
the invention has the following beneficial effects: the stable isotope labeled paclobutrazol and the synthesis method thereof provided by the invention use urea-containing material with isotope abundance of more than 99atom% 15 N 2 And hydrazine sulfate- 15 N 2 Is an isotope labeling source and synthesizes triazole- 15 N 3 Thereby further synthesizing paclobutrazol- 15 N 3 The 15N atom can not fall off in the reaction process, and the utilization rate of the stable isotope atom 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 99 percent, and the requirement of the product as a standard reagent for quantitatively detecting the paclobutrazol is met; high use value and good economical efficiency.
Drawings
FIG. 1 shows paclobutrazol- 15 N 3 The liquid chromatogram of (1).
FIG. 2 shows paclobutrazol- 15 N 3 Mass spectrum of (2).
Detailed Description
The invention is further described below with reference to the following figures and examples, which should not be construed as limiting the invention.
The invention utilizes the isotope labeling technology of 15N and utilizes urea-15N 2 And hydrazine sulfate-15N 2 As a stable 15N source, the triazole-15N is synthesized by two-step reaction 3 Thereby further providing a simple and high-efficiency preparation method of the stable isotope labeled paclobutrazol-15N 3 Methods of using the compounds.
The synthesis method of stable isotope labeled paclobutrazol provided by the invention comprises the following steps:
s1: using urea-15N 2 With formic acid to give formamide-15N;
the molecular structure is as follows:
s2: formamide-15N and hydrazine sulfate-15N 2 Reacting to obtain the triazole-15N marked by the stable isotope 3 ；
The molecular structure is as follows:
s3: triazole-15N 3 Reacting with chloropinacolone to obtain stable isotope labeled oxazolone-15N 3 (ii) a The molecular structure is as follows:
s4: azolone-15N 3 Reacting with p-chlorobenzyl bromide to obtain the stable isotope labeled chlorazolone-15N 3 ；
The molecular structure is as follows:
s5: chlorazolidone-15N 3 Reduced by potassium borohydride to obtain paclobutrazol-15N marked by stable isotope 3 ；
The molecular structure is as follows:
the solvent used can be a dry anhydrous solvent.
Examples
The molecular structure of the stable isotope labeled paclobutrazol of this example is as follows:
the preparation method comprises the following synthetic steps:
s1, adding 2.5g of urea-15N2, 4ml of formic acid into a reaction container, adjusting the temperature to 150-160 ℃ (the reaction rate is reduced when the temperature is too low, and the yield is reduced when the temperature is too high), reacting for 5-6 hours, and obtaining 2.0ml of colorless formamide-15N solution after the reaction is finished.
S2, adding formamide-15N 2.0ml (little reaction is not beneficial to subsequent purification, and much reaction is incomplete) into a reaction vessel, adjusting the temperature to 170-180 ℃, and adding 500mg hydrazine sulfate-15N in batches at the temperature 2 And after the addition is finished, reacting at 170-180 ℃ for 1-2 hours, after the reaction is finished, carrying out column purification, and carrying out purification operation according to the eluent ratio of dichloromethane/methanol =10 to obtain 160mg of triazole-15N 3 。
S3, adding 160mg of triazole-15N 3, 320mg of monochlorofonanone, 420mg of potassium carbonate, 18mg of 18-crown ether-6, and 5ml of ethyl acetate into a reaction container, adjusting the temperature to 60-80 ℃, reacting for 3-5 hours at the temperature, performing column purification after the reaction is finished, and performing purification operation to obtain 300mg of oxazolone-15N, wherein the eluent ratio of N-hexane/ethyl acetate =10 3 。
S4, adding 300mg of oxazolone-15N into a reaction vessel 3 5ml of toluene, 390mg of p-chlorobenzyl bromide and 15mg of benzyltriethylammonium chloride, adjusting the temperature to 60-80 ℃ after the addition is finished, adding 190mg of aqueous sodium hydroxide solution with the mass concentration of 40%, reacting for 5-6 hours at the temperature, adding 3ml of water after the reaction is finished, layering, extracting the aqueous layer by using 5ml of toluene, combining the organic layers, performing column purification, and performing purification operation to obtain 380mg of chlorzodone-15N 3 white solid, wherein the eluent ratio is N-hexane/ethyl acetate = 10.
S5, adding 380mg of chlorzodone-15N into a reaction vessel 3 Adding 38mg of potassium borohydride in batches into 5ml of methanol and 150mg of 30% sodium hydroxide aqueous solution at normal temperature, stirring at room temperature for 3-4 hours after the addition is finished, performing column purification after the reaction is finished, and performing purification operation to obtain 230mg of paclobutrazol-15N 3 A white solid.
The product sample obtained in this example was dissolved in methanol (. About.1 ppm) and subjected to purity and MS measurements, the spectra are shown in FIGS. 1 and 2. In the spectrogram 1, no obvious impurity peak is detected, and the chemical purity of the product of the paclobutrazol-15N 3 reaches more than 98 percent. In spectrum 2, the signal intensity is Relative Abundance (Relative Absundance), and MS data shows LC-MS m/z 297.2[ M + H + ], so the MS data is correct (molecular weight of paclobutrazol is 293.7, and molecular weight of paclobutrazol-15N 3 is 296.7).
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 (5)
1. Stable isotope labeled paclobutrazol- 15 N 3 The synthesis method is characterized by comprising the following steps:
s1: use of urea- 15 N reacts with formic acid to obtain formamide- 15 N；
S2: formamide ion-reaction 15 N and hydrazine sulfate- 15 N 2 Stable isotope labeled triazole- 15 N 3 ；
S3: triazole is reacted with 15 N 3 Reacting with chloropinacolone to obtain stable isotope labeled oxazolone- 15 N 3 ；
S4: azolone- 15 N 3 Reacting with p-chlorobenzyl bromide to obtain chlorzoxazone- 15 N 3 ；
S5: chloro-oxazolone- 15 N 3 Paclobutrazol-one obtained by potassium borohydride reduction 15 N 3 ；
The step S1 process is as follows: according to the weight portion, 2.0 to 2.5 portions of urea-plus-material are added into a reaction vessel 15 N 2 2.0 to 3.5 portions of formic acid, and the temperature is adjusted to be between 150 and 160 ℃; reacting for 3-5 hours at the temperature; after the reaction is finished, the solution is directly used for the next step;
the step S2 process is as follows: heating the solution of formamide-15N obtained in the step S1 to 170-190 DEG CAt the temperature, 0.5 part of hydrazine sulfate- 15 N 2 After the solid is added, reacting for 1-2 hours at 170-190 ℃; obtaining stable isotope labeled triazole- 15 N 3 ；
The step S3 comprises the following processes: according to the weight portion, 0.9 to 1.0 portion of triazole- 15 N 3 1.8 to 2.0 portions of chloropinacolone, 2.5 to 3.0 portions of potassium carbonate, 0.01 to 0.02 portion of 18-crown ether-6, 4.0 to 5.0 portions of ethyl acetate, raising the reaction temperature to 60 to 80 ℃, and reacting for 4 to 5 hours at the temperature of 60 to 80 ℃; filtering after the reaction is finished, purifying the filtrate by a column to obtain the stable isotope labeled oxazolone- 15 N 3 。
2. The synthesis method according to claim 1, wherein the step S4 is as follows: according to the weight portion, 0.9-1.0 portion of oxazolone- 15 N 3 7.0 to 8.0 parts of toluene, 1.3 to 1.5 parts of p-chlorobenzyl bromide and 0.04 to 0.06 part of benzyltriethylammonium chloride, raising the reaction temperature to 60 to 80 ℃, dripping 0.6 to 0.7 part of sodium hydroxide aqueous solution with the mass concentration of 40 percent at the temperature of 60 to 80 ℃ at the speed of 0.2 to 0.5mL for 1 second, and reacting for 4 to 5 hours at the temperature of 60 to 80 ℃; adding water for layering after the reaction is finished, concentrating an organic layer and purifying the organic layer by a column to obtain the chlorazol ketone-alpha-ketone labeled by the stable isotope 15 N 3 White solid.
3. The synthesis method according to claim 1, characterized in that the step S5 is carried out as follows: according to the weight portion, 0.9 to 1.0 portion of chlorzoxazone- 15 N 3 Adding 10-15 parts of methanol and 0.3-0.5 part of sodium hydroxide aqueous solution with the mass concentration of 30% into 0.1-0.2 part of potassium borohydride in batches, and reacting the reaction solution at room temperature for 3-5 hours; obtaining stable isotope labeled paclobutrazol-alpha-carboxylic acid after column purification 15 N 3 。
4. The synthesis method according to claim 1, wherein the step S5 further comprises: paclobutrazol using ethanol- 15 N 3 The white solid crude product is recrystallized and purified to obtain the paclobutrazol-alpha-olefin labeled by stable isotope 15 N 3 White solid product of (2).
5. Stable isotope labeled paclobutrazol-15N 3 Characterized by being prepared by the synthesis method of any one of claims 1 to 4 and having the following molecular structure:
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| (~(14)C-***基)-多效唑的合成;纪桂君等;《核农学报》;19900320(第01期);第43-44页 * |
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