CN105348324B - Organic phosphorus compound and its synthetic method and application containing tetrazolium heterocycle - Google Patents

Organic phosphorus compound and its synthetic method and application containing tetrazolium heterocycle Download PDF

Info

Publication number
CN105348324B
CN105348324B CN201510873890.1A CN201510873890A CN105348324B CN 105348324 B CN105348324 B CN 105348324B CN 201510873890 A CN201510873890 A CN 201510873890A CN 105348324 B CN105348324 B CN 105348324B
Authority
CN
China
Prior art keywords
substituted
heterocycle
phenyl
tetrazolium
base
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201510873890.1A
Other languages
Chinese (zh)
Other versions
CN105348324A (en
Inventor
刘佳
那日松
李洪连
张猛
蒋士军
彭伟东
郭线茹
周琳
李文明
何睿
卢世超
孙铖
侯伯男
王长青
刘炳杉
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Puyang Tianjian Biotechnology Co., Ltd.
Henan Agricultural University
Original Assignee
Henan Agricultural University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Henan Agricultural University filed Critical Henan Agricultural University
Priority to CN201510873890.1A priority Critical patent/CN105348324B/en
Publication of CN105348324A publication Critical patent/CN105348324A/en
Application granted granted Critical
Publication of CN105348324B publication Critical patent/CN105348324B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6524—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having four or more nitrogen atoms as the only ring hetero atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N57/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds
    • A01N57/18—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds
    • A01N57/24—Biocides, pest repellants or attractants, or plant growth regulators containing organic phosphorus compounds having phosphorus-to-carbon bonds containing heterocyclic radicals
    • 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
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
    • 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
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom

Landscapes

  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Pest Control & Pesticides (AREA)
  • Agronomy & Crop Science (AREA)
  • Plant Pathology (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

The present invention relates to the organic phosphorus compound containing tetrazolium heterocycle that a kind of organic phosphorus compound containing tetrazolium heterocycle, synthetic method and application, the present invention are provided, as shown in formula I or II.Its preparation method such as following steps：The multifarious substitution tetrazolium III and IV of generation is reacted using tetrazolium and halides; substitution tetrazolium III or IV and chlorine phosphate compounds react under alkali effect; obtain the organic phosphorus compound I and II containing tetrazolium heterocycle; the present invention provides a kind of new method simple and easy to apply for synthesis diversity tetrazolium phosphatase activity compound, and compound required for protection of the invention has no report.The synthetic method that the present invention is provided is simple and easy to apply, is suitable to prepare multifarious micromolecular compound storehouse.Compound involved in the present invention has carried out the related screening of nematodiasis activity.

Description

Organic phosphorus compound and its synthetic method and application containing tetrazolium heterocycle
Technical field
The invention belongs to organic compound synthesis technical field, it is related to a class tetrazolium phosphate derivative and its preparation side Method, and eelworm-killing activity application.
Background technology
Organophosphorus insecticide is the conventional agricultural insecticide of a class, and its insecticidal mechanism is to suppress cholinesterase activity, makes evil Worm is poisoned.Organophosphorus insecticide have it is various in style, using scope it is wide, insecticidal spectrum is wide, efficient speed kills that cross tolerance is few, legibility Malicious, degradable the advantages of, be provided simultaneously with tagging, stomach toxicity and it is stifling etc. it is different kill, worm effect；It has the disadvantage most of kind poison Property it is higher, the longevity of residure is short, is easily degraded in extraneous or animal body, is easily decomposed under alkalescence condition.Current organic phosphorous insecticide Development trend is as follows：1. low toxicity highly effective pesticide kind is developed.2. the compound of dissymmetrical structure is developed.3. heterocyclic chemical combination is developed Thing.
Tetrazole derivatives contain the tetrazole ring of plane azacyclo- skeleton structure, due to its pKa value close to carboxylic acid, and tool There is the plane extended system of about the same space requirement, can be used as the bioisostere of carboxyl, acid amides, triazole and imidazoles Body, improve compound bioactivity and pharmacokinetics in terms of play an important role, therefore tetrazole compound medicine with And application in agricultural chemicals is quite varied, such as olmesartan medoxomil, herbicide azimsulfuron (formula one).
The present invention develops the novel organophosphorus compound that a class contains tetrazolium heterocycle, inexpensive with efficient, low toxicity, Environment-friendly advantage.Satoh once reported the organic phosphorus compound containing tetrazolium heterocycle and phase of 4- methoxy-benzyls substitution Route (Tetrahedron Letters, 1995,36 (11), 1759-1762) is answered, the route that it is used is such as shown in (formula two).I A variation route being proposed, the synthesis of its intermediate is using document (Acta Crystallographica, Section E: Structure Reports Online, 2008,64 (1), o221,1-5), the method that another route then uses one pot of two step, It is easier to operate to overall route, it is adaptable to drug screening.Complete syntheti c route provided by the present invention, compared with original route Have the advantage that：(1) organic phosphorus compound of multifarious substitution tetrazolium, can more easily be obtained；(2), can obtain Obtain Satoh and propose 2 organic phosphorus compounds of the Benzyltetrazol of substitution that route cannot be obtained, so that synthesizing series has no report The organic phosphorus compound I (wherein do not include known compound V) containing tetrazolium heterocycle, particularly tetrazolium the position of substitution is not completely Same organic phosphorus compound II.In addition the present invention enters to the organic phosphorus compound I and II containing the tetrazolium heterocycle that apply protecting Gone correlation kill the biological activity determinations such as nematode.
The method that patent of the present invention is used compares with above-mentioned synthetic method, is more suitable for synthesizing multifarious in drug screening Bioactivity contains the organic phosphorus compound of tetrazolium heterocycle, such as：The diversity of tetrazolium the position of substitution, tetrazolium substituted radical it is various Property, phosphate ester group substitution diversity, so as to improve the screening active ingredients efficiency of novel pesticide.
The content of the invention
Replace answering for tetrazolium phosphate compounds, synthetic method and eelworm-killing activity it is an object of the invention to provide a kind of With.
The technical scheme is that：A kind of organic phosphorus compound containing tetrazolium heterocycle, it is described containing tetrazolium heterocycle The chemical formula of organic phosphorus compound is as shown in formula I or formula II：
In formula：X, Y, Z are O or S；
R1, R2Be the alkyl of C1~6 atom, or phenyl, substituted-phenyl, benzyl, substituted benzyl, the alkyl be methyl, Ethyl, propyl group, isopropyl, butyl, isobutyl group, the substituted-phenyl are halogen substituted phenyl, cyano group substituted-phenyl, nitro substitution Phenyl, trifluoromethyl substituted-phenyl, the alkyl-substituted phenyl of C1~6 carbon atom, the substituted benzyl be halogen substituted benzyl, Cyano group substituted benzyl, nitro substituted benzyl, trifluoromethyl substituted benzyl, the alkyl substituted benzyl base of C1~6 carbon atom；
R3Be the alkyl substituent of C1~6 atom, or phenyl, substituted-phenyl, benzyl, substituted benzyl, five yuan or hexa-atomic Heterocyclic substituent, five yuan or hexa-atomic substituted heterocycle substitution base, the alkyl substituent is methyl, ethyl, propyl group, isopropyl, fourth Base, isobutyl group；The substituted-phenyl is halogen substituted phenyl, cyano group substituted-phenyl, nitro substituted-phenyl, trifluoromethyl substituted benzene Base, the alkyl-substituted phenyl of C1~6 carbon atom, the substituted benzyl are halogen substituted benzyl, cyano group substituted benzyl, nitro take For benzyl, trifluoromethyl substituted benzyl, C1~6 carbon atom alkyl substituted benzyl base；Described five yuan or hexa-member heterocycle substitution base It is furyl, thienyl, pyridine radicals, described five yuan or hexa-atomic substituted heterocycle substitution base are halogen substituted heterocycle substitution base, cyano group Substituted heterocycle substitution base, nitro substituted heterocycle substitution base, trifluoromethyl substituted heterocycle substitution base, the alkyl of C1~6 carbon atom Substituted heterocycle replaces base.
The synthetic method of the described organic phosphorus compound containing tetrazolium heterocycle, tetrazole compound III or IV and chlorine phosphorus Acid esters compound prepares the organic phosphorus compound I or II containing tetrazolium heterocycle, the tetrazolium under butyl lithium effect Compound III or IV is as shown in general formula III or formula IV：
The synthetic method of the described organic phosphorus compound containing tetrazolium heterocycle, detailed step is as follows：
(1) mixture that necleophilic reaction prepares tetrazole compound III and IV is carried out by tetrazolium and halogenated compound, without Crossing separation carries out next step reaction；
(2) with chlorine phosphate compounds under butyl lithium effect, reaction is generated the mixture of tetrazole compound III and IV And separate acquisition the organic phosphorus compound I and II containing tetrazolium heterocycle.
Reaction dissolvent in the step (1) is DMF, tetrahydrofuran, Isosorbide-5-Nitrae dioxane, ether, Methyl tertiary butyl ether(MTBE), dichloromethane, one or more in chloroform.
The reaction time is 1 hour~24 hours in the step (2)；The reaction temperature is -40 DEG C~120 DEG C.
Organic phosphorus compound of the substitution containing tetrazolium heterocycle that the present invention is provided has eelworm-killing activity, can be as killing line The active ingredient of worm agent.
Organic phosphorus compound of the substitution containing tetrazolium heterocycle that the present invention is provided has certain sterilized to crop fungal disease And bacteriostatic activity, can be as the active ingredient of bactericide.
Organic phosphorus compound of the substitution containing tetrazolium heterocycle that the present invention is provided is to can be as the active ingredient of insecticide.
Organic phosphorus compound of the substitution containing tetrazolium heterocycle that the present invention is provided is to can be as the active ingredient of herbicide.
The beneficial effects of the invention are as follows：The multifarious organic phosphorus compound containing tetrazolium heterocycle of synthesis is more suitable for, such as： The diversity of tetrazolium the position of substitution, fragrant cyclosubstituted diversity, phosphate-based substituted diversity, raising new drug and novel pesticide Screening active ingredients efficiency.
Specific embodiment
Application in the plant disease that the compound of present invention synthesis causes to various cause of diseases such as preventing and treating nematode, fungies, phase Cause of disease example is closed to include but are not limited to：Plant nematode, such as Meloidogyne Meloidogyne, Heterodera Heterodera, Ditylenchus, grain Turbatrix Anguina, minute hand Turbatrix Longidorus, similes thorne Category Radophorus, Pratylenchus Pratylenchus, belong to nematodes；Oomycetes, such as pythium Pythium, false downy mildew Category Pseudoperonospora, Phytophthora Phytophthora, Peronospora Peronospora, white Phytophthora Peronophythora, with other category；Fungi Imperfecti, such as Fusarium Fusarium, Rhizoctonia Rhizoctonia, colletotrichum Colletotrichum, Curvularia Curvularia, with other category；Ascomycota, such as cochliobolus belong to Cochliobolus, red Mould category Gibberella, Erysiphe Erysiphe, Valsa Valsa, Claviceps Claviceps, Exoascus Taphrina, Venturia Venturia, mycosphaerella Mycosphaerella, Neovossia Neovossia, with other Category；And other such as bacteriums cause the pathogen of plant soil-borne diseases.Related disease example caused by related cause of disease include but It is not limited only to：The nematodiasises such as root knot nematode in tobacco, wheat cyst roundworm, sweet potato stem nematode, root-knot nematode；And rice blast Disease, wheat powdery mildew, wheat base rot disease, root rotof flax, wheat sharp eyespot, wheat scab, wheat corruption mildew, wheat is complete The soil-borne diseases such as erosion disease, Corn Stalk Rot, Maize Seedling Blight, Causal Organism of Maize Basal Stalk, corn corruption mildew.
Application of the compound of present invention synthesis in pest control and subterranean pest-insect disease.
The compound of present invention synthesis is to the application in controlling weeds.
Embodiment 1：Intermediate 1- benzyls -1H-TETRAZOLE III-1
In to the dry reaction bottle with thermometer, DMF 1mL and tetrazolium (2mmol), benzyl chloride are added (2.1mmol) and Anhydrous potassium carbonate (3mmol), is slowly warmed up 100 DEG C of reactions overnight under stirring.Reaction is cooled into room temperature, Pour into 4ml water.It is transferred in separatory funnel, is extracted with ethyl acetate, collect organic phase, washing, salt washing is dried, filtering.Filter Liquid is concentrated under reduced pressure into the mixture crude product of dry III-1 and IV-1, and recrystallization is separated out or uses ethyl acetate：Petroleum ether=1:5 (V/V) silicagel column purifying obtains white solid III-1, yield 43%.1H NMR (400MHz, Chloroform-d) δ 8.56 (d, J=5.5Hz, 1H), 7.51-7.25 (m, 6H), 5.61 (s, 2H).
Embodiment 2：1- (2- chlorobenzyls) -1H-TETRAZOLEs base-diethyl phosphate
Under nitrogen protection, 1- Benzyltetrazols (1mmol) are added in dry reactor, add 10 milliliters of drying Tetrahydrofuran.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, at a temperature of this Reaction 1 hour, is then added dropwise diethyl chloro-phosphate (1mmol, 1eq).After dripping, this temperature is kept 1 hour.It is warmed to room temperature, Stirring 1 hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses second Acetoacetic ester：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 91%.1H NMR (400MHz, Chloroform-d) δ 7.50- (td, J=7.1,1.2Hz, the 6H) of 7.33 (m, 5H) .4.49 (d, J=8.7Hz, 2H), 4.28-4.03 (m, 4H), 1.3413C NMR (101MHz, CDCl3) δ 134.48,134.47,129.10,128.99,128.88,111.19,111.14,65.11, 65.05,53.66,53.64,15.94,15.87.IR (film) νmax3454,2986,2229,1638,1456,1445,1371, 1282,1210,1163,1099,1014,949,799,783,707,604,568,530,484,469,455,441,407.HRMS (ESI), calculated value：C12H18N4O3P+[M+H]+297.1111, measured value：297.1114.
Embodiment 3：1- (2- chlorobenzyls) -1H-TETRAZOLEs base-diethyl phosphate
In to the dry reaction bottle with thermometer, DMF 1mL and tetrazolium (2mmol), 2- chlorine chlorine are added Benzyl (2.1mmol) and Anhydrous potassium carbonate (3mmol), are slowly warmed up 100 DEG C of reactions overnight under stirring.Reaction is cooled into room Temperature, pours into 4ml water.It is transferred in separatory funnel, is extracted with ethyl acetate, collect organic phase, washing, salt washing is dried, mistake Filter.Filtrate decompression be concentrated to dryness III-2 and IV-2 mixture crude product, yield 95%.
Under nitrogen protection, the mixture crude product of III-2 and IV-2 is added in dry reactor, adds 10 millis The dry tetrahydrofuran for rising.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, Reacted 1 hour at a temperature of this, diethyl chloro-phosphate (2.1mmol) is added dropwise.After dripping, this temperature is kept 1 hour.Rise to room Temperature, stirs 1 hour, and raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, Use ethyl acetate：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 41.5%.1H NMR (400MHz, Chloroform-d) δ 7.56-7.31 (m, 4H), 4.67 (dd, J=7.6,2.7Hz, 2H), 4.31-4.14 (m, 4H), 1.35-1.24 (m, 6H)13C NMR (101MHz, CDCl3) δ 135.83,135.52,135.38,134.47,133.84,133.62,130.38,129.62, 129.33,129.06,128.69,127.70,65.79,65.67,62.66,62.62,15.93,15.86.IR (film) νmax 3482., 2985,2935,2872,2230,1637,1595,1575,1477,1444,1394,1371,1279,1207,1164, 1113,1099,1014,758,682,605,572,535,464,415,403.HRMS (ESI), calculated value：C12H17ClN4O3P+ [M+H]+331.0721, measured value：331.0723
Embodiment 4:2- (2- chlorobenzyls) -2H- tetrazole radicals-diethyl phosphate
In to the dry reaction bottle with thermometer, DMF 1mL and tetrazolium (2mmol), 2- chlorine chlorine are added Benzyl (2.1mmol) and Anhydrous potassium carbonate (3mmol), are slowly warmed up 100 DEG C of reactions overnight under stirring.Reaction is cooled into room Temperature, pours into 4ml water.It is transferred in separatory funnel, is extracted with ethyl acetate, collect organic phase, washing, salt washing is dried, mistake Filter.Filtrate decompression be concentrated to dryness III-2 and IV-2 mixture crude product, yield 95%.
Under nitrogen protection, the mixture crude product of III-2 and IV-2 is added in dry reactor, adds 10 millis The dry tetrahydrofuran for rising.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, Reacted 1 hour at a temperature of this, the diethyl chloro-phosphate (2.1mmol) of dropwise addition.After dripping, this temperature is kept 1 hour.Rise to room Temperature, stirs 1 hour, and raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, Use ethyl acetate：Petroleum ether=1:8 (V/V) cross silicagel column purifying, yield 37.3%.1H NMR (400MHz, Chloroform- D) (m, the 6H) of δ 7.64-7.21 (m, 4H), 5.20 (d, J=7.2Hz, 2H), 4.24-4.09 (m, 4H), 1.41-1.3113C NMR (101MHz, CDCl3) δ 133.84,133.76,132.88,129.55,129.39,129.23,126.94,66.12,66.07, 64.01,63.95,16.11,16.04.IR (film) νmax3448,2927,2853,1596,1493,1413,1340,1266, 1194,1128,1091,1015,982,875,848,823,785,753,593.HRMS (ESI), calculated value：C12H17ClN4O3P+ [M+H]+331.0721, measured value：331.0724.
Embodiment 5:1- (4- chlorobenzyls) -1H-TETRAZOLEs base-diethyl phosphate
In to the dry reaction bottle with thermometer, DMF 1mL and tetrazolium (2mmol), 4- chlorine chlorine are added Benzyl (2.1mmol) and Anhydrous potassium carbonate (3mmol), are slowly warmed up 100 DEG C of reactions overnight under stirring.Reaction is cooled into room Temperature, pours into 4ml water.It is transferred in separatory funnel, is extracted with ethyl acetate, collect organic phase, washing, salt washing is dried, mistake Filter.Filtrate decompression be concentrated to dryness III-3 and IV-3 mixture crude product, yield 95%.
Under nitrogen protection, the mixture crude product of III-3 and IV-3 is added in dry reactor, adds 10 millis The dry tetrahydrofuran for rising.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, Reacted 1 hour at a temperature of this, diethyl chloro-phosphate (1mmol) is added dropwise.After dripping, this temperature is kept 1 hour.It is warmed to room temperature, Stirring 1 hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses second Acetoacetic ester：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 42.7%.1H NMR (400MHz, Chloroform-d) δ 7.40 (s, 4H), 4.48 (d, J=8.8Hz, 2H), 4.29-4.09 (m, 4H), 1.37 (m, J=7.1,1.1Hz, 6H)13C NMR (101MHz, CDCl3) δ 135.20,132.95,132.94,130.26,129.24,110.96,110.90,65.27,65.21, 52.88,52.85,15.96,15.89.IR (film) νmax3455,2985,2230,1638,1493,1323,1280,1163, 1093,1014,924,805,658,593,539,509,472,444,409.HRMS (ESI), calculated value：C12H17ClN4O3P+[M +H]+331.0721, measured value：331.0725.
Embodiment 6:2- (4- chlorobenzyls) -2H- tetrazole radicals-diethyl phosphate
In to the dry reaction bottle with thermometer, DMF 1mL and tetrazolium (2mmol), 4- chlorine chlorine are added Benzyl (2.1mmol) and Anhydrous potassium carbonate (3mmol), are slowly warmed up 100 DEG C of reactions overnight under stirring.Reaction is cooled into room Temperature, pours into 4ml water.It is transferred in separatory funnel, is extracted with ethyl acetate, collect organic phase, washing, salt washing is dried, mistake Filter.Filtrate decompression be concentrated to dryness III-3 and IV-3 mixture crude product, yield 95%.
Under nitrogen protection, the mixture crude product of III-3 and IV-3 is added in dry reactor, adds 10 millis The dry tetrahydrofuran for rising.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, Reacted 1 hour at a temperature of this, diethyl chloro-phosphate (1mmol) is added dropwise.After dripping, this temperature is kept 1 hour.It is warmed to room temperature, Stirring 1 hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses second Acetoacetic ester：Petroleum ether=1:8 (V/V) cross silicagel column purifying, yield 35.5%.1H NMR (400MHz, Chloroform-d) δ (td, J=7.1,1.1Hz, the 6H) of 7.40 (s, 4H), 4.48 (d, J=8.8Hz, 2H), 4.30-4.04 (m, 4H), 1.3713C NMR (101MHz, CDCl3) δ 135.20,132.95,132.94,130.26,129.24,110.96,110.90,65.27, 65.21,52.88,52.85,15.96,15.89.IR (film) νmax3406,2931,2899,2872,2858., 1650, 1638,1633,1593,1267,1162,1024,976,753,563,536,507,443.HRMS (ESI), calculated value： C12H17ClN4O3P+[M+H]+331.0721, measured value：331.0727.
Embodiment 7：1- (2- luorobenzyls) -1H-TETRAZOLEs base-diethyl phosphate：
In to the dry reaction bottle with thermometer, DMF 1mL and tetrazolium (2mmol), 2- fluorine chlorine are added Benzyl (2.1mmol) and Anhydrous potassium carbonate (3mmol), are slowly warmed up 100 DEG C of reactions overnight under stirring.Reaction is cooled into room Temperature, pours into 4ml water.It is transferred in separatory funnel, is extracted with ethyl acetate, collect organic phase, washing, salt washing is dried, mistake Filter.Filtrate decompression be concentrated to dryness III-4 and IV-4 mixture crude product, yield 95%.
Under nitrogen protection, the mixture crude product of III-4 and IV-4 is added in dry reactor, adds 10 millis The dry tetrahydrofuran for rising.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, Reacted 1 hour at a temperature of this, diethyl chloro-phosphate (2.1mmol) is added dropwise.After dripping, this temperature is kept 1 hour.Rise to room Temperature, stirs 1 hour, and raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, Use ethyl acetate：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 41.8%.1H NMR (400MHz, Chloroform-d) δ 7.50-7.35 (m, 2H), 7.24-7.09 (m, 2H), 4.58 (dd, J=7.9,1.0Hz, 2H), 4.26-4.09 (m, 4H), 1.36 (td, J=7.1,1.1Hz, 6H)13C NMR (101MHz, CDCl3) δ 162.32,159.84,131.33,131.29,131.25, 124.64,124.61,121.41,121.38,121.26,121.24,115.98,115.77,110.83,110.77,65.32, 65.26,50.64,47.26,47.23,47.20,15.95,15.88.IR (film) νmax3452,2993,2926,2230, 1643,1493,1457,1278,1233,1193,1164,1108,1031,759,688,604,537,515,483,459,445, 422.HRMS (ESI), calculated value：C12H17FN4O3P+[M+H]+315.1017, measured value：315.1021.
Embodiment 8：2- (2- luorobenzyls) -2H- tetrazole radicals-diethyl phosphate：
In to the dry reaction bottle with thermometer, DMF 1mL and tetrazolium (2mmol), 2- fluorine chlorine are added Benzyl (2.1mmol) and Anhydrous potassium carbonate (3mmol), are slowly warmed up 100 DEG C of reactions overnight under stirring.Reaction is cooled into room Temperature, pours into 4ml water.It is transferred in separatory funnel, is extracted with ethyl acetate, collect organic phase, washing, salt washing is dried, mistake Filter.Filtrate decompression be concentrated to dryness III-4 and IV-4 mixture crude product, yield 95%.
Under nitrogen protection, the mixture crude product of III-4 and IV-4 is added in dry reactor, adds 10 millis The dry tetrahydrofuran for rising.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, Reacted 1 hour at a temperature of this, diethyl chloro-phosphate (2.1mmol) is added dropwise.After dripping, this temperature is kept 1 hour.Rise to room Temperature, stirs 1 hour, and raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, Use ethyl acetate：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 31.4%.1H NMR (400MHz, Chloroform-d) δ 7.50-7.35 (m, 2H), 7.24-7.09 (m, 2H), 4.58 (dd, J=7.9,1.0Hz, 2H), 4.26-4.09 (m, 4H), 1.36 (td, J=7.1,1.1Hz, 6H) .IR (film) νmax3501,2990,2926,2230,1623,1493,1457,1378, 1233,1163,1113,1001,751,688,614,577,525,483,449.HRMS (ESI), calculated value：C12H17FN4O3P+ [M+H]+315.1017, measured value：315.1019.
Embodiment 9：1- (3- luorobenzyls) -1H-TETRAZOLEs base-diethyl phosphate
In to the dry reaction bottle with thermometer, DMF 1mL and tetrazolium (2mmol), 3- fluorine chlorine are added Benzyl (2.1mmol) and Anhydrous potassium carbonate (3mmol), are slowly warmed up 100 DEG C of reactions overnight under stirring.Reaction is cooled into room Temperature, pours into 4ml water.It is transferred in separatory funnel, is extracted with ethyl acetate, collect organic phase, washing, salt washing is dried, mistake Filter.Filtrate decompression be concentrated to dryness III-5 and IV-5 mixture crude product, yield 95%.
Under nitrogen protection, the mixture crude product of III-5 and IV-5 is added in dry reactor, adds 10 millis The dry tetrahydrofuran for rising.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, Reacted 1 hour at a temperature of this, diethyl chloro-phosphate (1mmol) is added dropwise.After dripping, this temperature is kept 1 hour.It is warmed to room temperature, Stirring 1 hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses second Acetoacetic ester：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 42%.1H NMR (400MHz, Chloroform-d) δ 7.45- 7.33 (m, 1H), 7.26-7.04 (m, 3H), 4.49 (d, J=8.8Hz, 2H), 4.26-4.12 (m, 4H), 1.37 (td, J= 7.1,1.1Hz, 6H)13C NMR (101MHz, CDCl3) δ 164.12,161.65,136.83,136.81,136.76,136.74, 130.73,130.65,124.46,124.43,116.24,116.03,115.83,115.61,110.95,110.89,65.32, 65.26,52.98,52.96,52.93,15.95,15.88.IR (film) νmax3509,2987,2937,2226,1618, 1593,1489,1452,1371,1319,1282,1164,1143,1099,1008,946,799,747,681,616,576, 542,459.HRMS (ESI), calculated value：C12H17FN4O3P+[M+H]+315.1017, measured value：315.1022.
Embodiment 10：2- (3- luorobenzyls) -2H- tetrazole radicals-diethyl phosphate
In to the dry reaction bottle with thermometer, DMF 1mL and tetrazolium (2mmol), 3- fluorine chlorine are added Benzyl (2.1mmol) and Anhydrous potassium carbonate (3mmol), are slowly warmed up 100 DEG C of reactions overnight under stirring.Reaction is cooled into room Temperature, pours into 4ml water.It is transferred in separatory funnel, is extracted with ethyl acetate, collect organic phase, washing, salt washing is dried, mistake Filter.Filtrate decompression be concentrated to dryness III-5 and IV-5 mixture crude product, yield 95%.
Under nitrogen protection, the mixture crude product of III-5 and IV-5 is added in dry reactor, adds 10 millis The dry tetrahydrofuran for rising.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, Reacted 1 hour at a temperature of this, diethyl chloro-phosphate (1mmol) is added dropwise.After dripping, this temperature is kept 1 hour.It is warmed to room temperature, Stirring 1 hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses second Acetoacetic ester：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 33%.1H NMR (400MHz, Chloroform-d) δ 7.72- 6.92 (m, 4H), 4.58 (dd, J=7.8,1.0Hz, 2H), 4.36-3.99 (m, 4H), 1.35 (td, J=7.1,1.2Hz, 6H) .IR(film)νmax3508,2987,2937,2226,1618,1593,1489,1452,1371,1319,1282,1164, 1143,1099,1008,946,876,799,747,681,616,576,542,459,440,428.HRMS (ESI), calculated value： C12H17FN4O3P+[M+H]+315.1017, measured value：315.1023.
Embodiment 11：1- (4- luorobenzyls) -1H-TETRAZOLEs base-diethyl phosphate
Under nitrogen protection, 1- (4- fluorine) Benzyltetrazol (1mmol) is added in dry reactor, adds 10 milliliters Dry tetrahydrofuran.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, this At a temperature of react 1 hour, be added dropwise diethyl chloro-phosphate (1mmol).After dripping, this temperature is kept 1 hour.It is warmed to room temperature, stirs Mix 1 hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses acetic acid Ethyl ester：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 81%.1H NMR (400MHz, Chloroform-d) δ 7.52- 7.39 (m, 2H), 7.18-7.07 (m, 2H), 4.49 (d, J=8.7Hz, 2H), 4.30-4.00 (m, 4H), 1.37 (td, J= 7.1,1.1Hz, 6H)13C NMR (101MHz, CDCl3) δ 164.37,161.90,130.91,130.83,130.40,116.13, 115.91,111.02,110.97,65.20,65.14,52.89,52.87,15.95,15.88.IR (film) νmax3509, 2987,2941,2226,1604,1512,1445,1395,1371,1325,1276,1225,1161,1100,1007,922, 842,800,765,597,553,439.HRMS (ESI), calculated value：C12H17FN4O3P+[M+H]+315.1017, measured value： 315.1017。
Embodiment 12:1- (2,4- chlorobenzyl) -1H-TETRAZOLEs base-diethyl phosphate
In to the dry reaction bottle with thermometer, DMF 1mL and tetrazolium (2mmol), 2,4- bis- are added Chlorobenzyl chloride (2.1mmol) and Anhydrous potassium carbonate (3mmol), are slowly warmed up 100 DEG C of reactions overnight under stirring.Reaction is cooled to Room temperature, pours into 4ml water.It is transferred in separatory funnel, is extracted with ethyl acetate, collect organic phase, washing, salt washing is dried, mistake Filter.Filtrate decompression be concentrated to dryness III-7 and IV-7 mixture crude product, yield 95%.
Under nitrogen protection, the mixture crude product of III-7 and IV-7 is added in dry reactor, adds 10 millis The dry tetrahydrofuran for rising.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, Reacted 1 hour at a temperature of this, diethyl chloro-phosphate (1mmol) is added dropwise.After dripping, this temperature is kept 1 hour.It is warmed to room temperature, Stirring 1 hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses second Acetoacetic ester：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 42.2%.1H NMR (400MHz, Chloroform-d) δ 7.45-7.26 (m, 3H), 5.04 (d, J=8.8Hz, 2H), 4.19-3.98 (m, 4H), 1.36 (td, J=7.1,1.1Hz, 6H) .IR(film)νmax3405,2985,2230,1638,1493,1323,1260,1167,1093,1014,974,805,750, 658,593,539,509,472,444.HRMS (ESI), calculated value C12H16Cl2N4O3P+[M+H]+365.0332, measured value： 365.0339。
Embodiment 13:2- (2,4- chlorobenzyl) -2H- tetrazole radicals-diethyl phosphate
In to the dry reaction bottle with thermometer, DMF 1mL and tetrazolium (2mmol), 2,4- bis- are added Chlorobenzyl chloride (2.1mmol) and Anhydrous potassium carbonate (3mmol), are slowly warmed up 100 DEG C of reactions overnight under stirring.Reaction is cooled to Room temperature, pours into 4ml water.It is transferred in separatory funnel, is extracted with ethyl acetate, collect organic phase, washing, salt washing is dried, mistake Filter.Filtrate decompression be concentrated to dryness III-7 and IV-7 mixture crude product, yield 95%.
Under nitrogen protection, the mixture crude product of III-4 and IV-4 is added in dry reactor, adds 10 millis The dry tetrahydrofuran for rising.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, Reacted 1 hour at a temperature of this, diethyl chloro-phosphate (1mmol) is added dropwise.After dripping, this temperature is kept 1 hour.It is warmed to room temperature, Stirring 1 hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses second Acetoacetic ester：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 32.3%.1H NMR (400MHz, Chloroform-d) δ 7.49-7.26 (m, 3H), 5.13 (d, J=8.8Hz, 2H), 4.21-4.08 (m, 4H), 1.34 (td, J=7.1,1.1Hz, 6H) .IR(film)νmax3478,2985,2230,1638,1473,1393,1279,1163,1097,1014,934,805,758, 658,593,539,444,401.HRMS (ESI), calculated value：C12H16Cl2N4O3P+[M+H]+365.0332, measured value： 365.0337。
Embodiment 14：1- (2- cyanobenzyls) -1H-TETRAZOLEs base-diethyl phosphate
Under nitrogen protection, 1- (2- cyano group) Benzyltetrazol (1mmol) is added in dry reactor, adds 10 millis The dry tetrahydrofuran for rising.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, Reacted 1 hour at a temperature of this, diethyl chloro-phosphate (1mmol) is added dropwise.After dripping, this temperature is kept 1 hour.It is warmed to room temperature, Stirring 1 hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses second Acetoacetic ester：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 89%.1H NMR (400MHz, Chloroform-d) δ 7.80- 6.95 (m, 4H), 4.71 (dd, J=7.3,1.0Hz, 2H), 4.31-3.99 (m, 4H), 1.35 (td, J=7.1,1.1Hz, 6H) .IR(film)νmax3508,2987,2937,2240,2130,1618,1593,1489,1450,1378,1319,1282, 1164,1140,1089,989,946,877,745,685,624,586,535,455,441.HRMS (ESI), calculated value： C13H17N5O3P+[M+H]+322.1064, measured value：322.1067.
Embodiment 15：1- (2- methyl-benzyls) -1H-TETRAZOLEs base-diethyl phosphate
Under nitrogen protection, 1- (2- methyl) Benzyltetrazol (1mmol) is added in dry reactor, adds 10 millis The dry tetrahydrofuran for rising.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, Reacted 1 hour at a temperature of this, diethyl chloro-phosphate (1mmol) is added dropwise.After dripping, this temperature is kept 1 hour.It is warmed to room temperature, Stirring 1 hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses second Acetoacetic ester：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 86%.1H NMR (400MHz, Chloroform-d) δ 7.56- 7.11 (m, 4H), 4.49 (d, J=8.7Hz, 2H), 4.31-4.00 (m, 4H), 2.28 (s, 3H), 1.32 (td, J=7.1, 1.1Hz, 6H) .3456,2980,2880,2440,1635,1455,1378,1282,1210,1168,1082,1014,952, 801,787,712,614,582,535,484.HRMS (ESI), calculated value：C13H20N4O3P+[M+H]+331.0721, measured value： 311.1268。
Embodiment 16：1- (2- chlorphenyls) -1H-TETRAZOLEs base-diethyl phosphate
Under nitrogen protection, 1- (2- chlorine) phenyltetrazole (1mmol) is added in dry reactor, adds 10 milliliters Dry tetrahydrofuran.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, this At a temperature of react 1 hour, be added dropwise diethyl chloro-phosphate (1mmol).After dripping, this temperature is kept 1 hour.It is warmed to room temperature, stirs Mix 1 hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses acetic acid Ethyl ester：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 87.2%.1H NMR (400MHz, Chloroform-d) δ 7.78- 6.96 (m, 4H), 4.38 (d, J=8.8Hz, 2H), 4.36-3.98 (m, 4H), 1.38-1.24 (m, 6H) .IR (film) νmax 3487., 2980,2920,2880,2240,1638,1590,1572,1480,1442,1390,1375,1280,1203,1166, 1112,1090,1012,755,690,610,572,525.HRMS (ESI), calculated value：C11H15ClN4O3P+[M+H]+ 317.0565, measured value：317.0569.
Embodiment 17：1- (1- methyl) -1H-TETRAZOLEs base-diethyl phosphate
Under nitrogen protection, 1- methyl tetrazolium (1mmol) is added in dry reactor, adds 10 milliliters of drying Tetrahydrofuran.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, at a temperature of this Reaction 1 hour, is added dropwise diethyl chloro-phosphate (1mmol).After dripping, this temperature is kept 1 hour.It is warmed to room temperature, stirring 1 is small When, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses ethyl acetate： Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 87.2%.1H NMR (400MHz, Chloroform-d) δ 4.24 (s, 3H), 4.22-4.04 (m, 4H), 1.37-1.24 (m, 6H) .IR (film) νmax3508,2987,2937,2226,1618,1593, 1489,1452,1371,1319,1282,1164,1143,1099,1008,946,876,799,747,681,616,576,542, 459,440,428.HRMS (ESI), calculated value：C6H14N4O3P+[M+H]+221.0798, measured value：221.0801.
Embodiment 18：1- (2- pyridines) -1H-TETRAZOLEs base-diethyl phosphate
Under nitrogen protection, 1- (2- pyridines) tetrazolium (1mmol) is added in dry reactor, adds 10 milliliters Dry tetrahydrofuran.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, this temperature The lower reaction of degree 1 hour, is added dropwise diethyl chloro-phosphate (1mmol).After dripping, this temperature is kept 1 hour.It is warmed to room temperature, stirring 1 Hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses acetic acid second Ester：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 87.2%.1H NMR (400MHz, Chloroform-d) δ 7.80- 6.99 (m, 4H), 4.62 (dd, J=7.3,1.0Hz, 2H), 4.29-4.02 (m, 4H), 1.35 (td, J=7.1,1.1Hz, 6H) .IR(film)νmax3450,3348,3260,3100,2980,2226,1610,1592,1488,1447,1375,1320, 1289,1124,1089,1018,945,877,786,689,578,545,434.HRMS (ESI), calculated value：C11H17N5O3P+[M +H]+298.1064, measured value：298.1065.
Embodiment 19：1- (2- furans) -1H-TETRAZOLEs base-diethyl phosphate
Under nitrogen protection, 1- (2- furans) tetrazolium (1mmol) is added in dry reactor, adds 10 milliliters Dry tetrahydrofuran.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, this temperature The lower reaction of degree 1 hour, is added dropwise diethyl chloro-phosphate (1mmol).After dripping, this temperature is kept 1 hour.It is warmed to room temperature, stirring 1 Hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses acetic acid second Ester：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 87.2%.1H NMR (400MHz, Chloroform-d) δ 7.64- 6.99 (m, 3H), 4.55 (d, J=8.8Hz, 2H), 4.24-4.04 (m, 4H), 1.41-1.28 (m, 6H) .IR (film) νmax 3100,2997,2942,2260,1609,1593,1560,1510,1478,1378,1320,1285,1165,1089,1010, 987,845,798,747,689,610,578,548,454.HRMS (ESI), calculated value：C10H16N4O4P+[M+H]+287.0904, Measured value：287.0909.
Embodiment 20：1- (2- thiophene) -1H-TETRAZOLEs base-diethyl phosphate
Under nitrogen protection, 1- (2- furans) tetrazolium (1mmol) is added in dry reactor, adds 10 milliliters Dry tetrahydrofuran.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, this temperature The lower reaction of degree 1 hour, is added dropwise diethyl chloro-phosphate (1mmol).After dripping, this temperature is kept 1 hour.It is warmed to room temperature, stirring 1 Hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses acetic acid second Ester：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 87.2%.1H NMR (400MHz, Chloroform-d) δ 7.58- 6.97 (m, 3H), 4.53 (d, J=8.7Hz, 2H), 4.23-4.01 (m, 4H), 1.38-1.29 (m, 6H) .IR (film) νmax 3102,3060,2998,2268,1593,1560,1522,1510,1455,1425,1380,1319,1289,1160,1089, 1008,987,935,848,788,747,680,612,578,548.HRMS (ESI), calculated value：C10H16N4O3PS+[M+H]+ 303.0675, measured value：303.0677.
Embodiment 21：O, O- diethyl-[1- (2- chlorobenzyls) -1H-TETRAZOLE base]-thiophosphate
Under nitrogen protection, 1- (2- chloros) Benzyltetrazol (1mmol) is added in dry reactor, adds 10 millis The dry tetrahydrofuran for rising.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, Reacted 1 hour at a temperature of this, O is added dropwise, O- diethyl sulfides are for chlorine phosphate (1mmol).After dripping, this temperature is kept 1 hour. It is warmed to room temperature, stirs 1 hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent is obtained Crude product, uses ethyl acetate：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 87.2%.1H NMR (400MHz, Chloroform-d) δ 7.62-7.25 (m, 4H), 4.65 (d, J=7.2Hz, 2H), 4.23-4.05 (m, 4H), 1.42-1.29 (m, 6H) .IR (film) νmax3480., 2980,2922,2860,2240,1605,1580,1482,1460,1389,1260, 1208,1165,1108,1099,1014,754,675,605,582,540,484.HRMS (ESI), calculated value： C12H17ClN4O2PS+[M+H]+347.0493, measured value：347.0497.
Embodiment 22：O, O- diphenyl-[1- (2- chlorobenzyls) -1H-TETRAZOLE base]-thiophosphate
Under nitrogen protection, 1- (2- chloros) Benzyltetrazol (1mmol) is added in dry reactor, adds 10 millis The dry tetrahydrofuran for rising.Less than -10 DEG C are cooled to, butyl lithium (2.2mmol, 1M, 1.1eq) is slowly added dropwise.After completion of dropping, Reacted 1 hour at a temperature of this, diphenyl phosphate chloride (1mmol) is added dropwise.After dripping, this temperature is kept 1 hour.It is warmed to room temperature, Stirring 1 hour, raw material reacts completely.Washing 2 times, is dried with anhydrous magnesium sulfate.Filtering, spin concentration solvent obtains crude product, uses second Acetoacetic ester：Petroleum ether=1:8 (V/V) silicagel columns are purified, yield 87.2%.1H NMR(500MHz,Chloroform-d)δ 7.56-6.72 (m, 14H), 5.49 (d, J=0.9Hz, 2H) .IR (film) νmax3509,3063,2980,1620,1589, 1491,1455,1361,1295,1183,1084,1023,946,822,766,747,689,525,467,423.HRMS (ESI), Calculated value：C20H17ClN4O3P+[M+H]+427.0721, measured value：427.0725.
Compound eelworm-killing activity is tested
Table 1 is medicine Nematicidal Activity result.
Prepare 50ppm liquids；Two ages of the nematodes such as root knot nematode in tobacco, wheat SCN, sweet potato stem nematode will be collected The suspension of larva, is settled to 50mL, 1mL is taken after shaking up and instills counting ware, is counted under anatomical lens, determines nematode concentration.Match somebody with somebody 50ppm liquids processed, wherein contain sterilized water, DMSO and Tween 80 equal solvent and cosolvent.Eelworm-killing activity life is carried out with liquid Thing is determined, and so that, as blank, each sample repeats experiment 3 times without liquid medicine, each sample is tested every time and is done at 4 repetitions Reason.24 hours corrected mortalities are calculated, as a result as shown in table 1.

Claims (5)

1. a kind of organic phosphorus compound containing tetrazolium heterocycle, it is characterised in that：The organophosphor chemical combination containing tetrazolium heterocycle The chemical formula of thing is as shown in formula I or formula II：
In formula：X, Y, Z are O or S；
R1, R2It is the alkyl of C1~6 atom, or phenyl, substituted-phenyl, benzyl, substituted benzyl, the alkyl is methyl, second Base, propyl group, isopropyl, butyl, isobutyl group, the substituted-phenyl are halogen substituted phenyl, cyano group substituted-phenyl, nitro substituted benzene Base, trifluoromethyl substituted-phenyl, the alkyl-substituted phenyl of C1~6 carbon atom, the substituted benzyl are halogen substituted benzyl, cyanogen Base substituted benzyl, nitro substituted benzyl, trifluoromethyl substituted benzyl, the alkyl substituted benzyl base of C1~6 carbon atom；
R3It is the alkyl substituent of C1~6 atom, or phenyl, substituted-phenyl, benzyl, substituted benzyl, five yuan or hexa-member heterocycle take Dai Ji, five yuan or hexa-atomic substituted heterocycle substitution base, the alkyl substituent is methyl, ethyl, propyl group, isopropyl, butyl, isobutyl Base；The substituted-phenyl be halogen substituted phenyl, cyano group substituted-phenyl, nitro substituted-phenyl, trifluoromethyl substituted-phenyl, C1~ 6 alkyl-substituted phenyls of carbon atom, the substituted benzyl be halogen substituted benzyl, cyano group substituted benzyl, nitro substituted benzyl, The alkyl substituted benzyl base of trifluoromethyl substituted benzyl, C1~6 carbon atom；Described five yuan or hexa-member heterocycle substitution base be furans Base, thienyl, pyridine radicals, described five yuan or hexa-atomic substituted heterocycle substitution base be halogen substituted heterocycle substitution base, cyano group substitution it is miscellaneous Ring substituents, nitro substituted heterocycle substitution base, trifluoromethyl substituted heterocycle substitution base, the alkyl of C1~6 carbon atom replace miscellaneous Ring substituents.
2. the synthetic method of the organic phosphorus compound containing tetrazolium heterocycle according to claim 1, it is characterised in that：Tetrazolium Compound III or IV and chlorine phosphate compounds prepare the organophosphor containing tetrazolium heterocycle under butyl lithium effect Compound I or II, the tetrazole compound III or IV is as shown in general formula III or formula IV：
3. the synthetic method of the organic phosphorus compound containing tetrazolium heterocycle according to claim 2, it is characterised in that：
(1) mixture that necleophilic reaction prepares tetrazole compound III and IV is carried out by tetrazolium and halogenated compound, without undue From carrying out next step reaction；
(2) with chlorine phosphate compounds under butyl lithium effect, reaction is generated and divided the mixture of tetrazole compound III and IV From acquisition the organic phosphorus compound I and II containing tetrazolium heterocycle.
4. the synthetic method of the organic phosphorus compound containing tetrazolium heterocycle according to claim 3, it is characterised in that：It is described Reaction dissolvent in step (1) is DMF, tetrahydrofuran, Isosorbide-5-Nitrae dioxane, ether, methyl tertiary butyl ether(MTBE), Dichloromethane, one or more in chloroform.
5. the synthetic method of the organic phosphorus compound containing tetrazolium heterocycle according to claim 3, it is characterised in that：Institute The reaction time is 1 hour~24 hours in stating step (2)；The reaction temperature is -40 DEG C~120 DEG C.
CN201510873890.1A 2015-12-02 2015-12-02 Organic phosphorus compound and its synthetic method and application containing tetrazolium heterocycle Active CN105348324B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510873890.1A CN105348324B (en) 2015-12-02 2015-12-02 Organic phosphorus compound and its synthetic method and application containing tetrazolium heterocycle

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510873890.1A CN105348324B (en) 2015-12-02 2015-12-02 Organic phosphorus compound and its synthetic method and application containing tetrazolium heterocycle

Publications (2)

Publication Number Publication Date
CN105348324A CN105348324A (en) 2016-02-24
CN105348324B true CN105348324B (en) 2017-06-30

Family

ID=55324405

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510873890.1A Active CN105348324B (en) 2015-12-02 2015-12-02 Organic phosphorus compound and its synthetic method and application containing tetrazolium heterocycle

Country Status (1)

Country Link
CN (1) CN105348324B (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106083929B (en) * 2016-07-01 2017-12-15 安徽农业大学 A kind of tetrazolium phosphate compound and synthetic method with eelworm-killing activity
CN109673666A (en) * 2018-12-22 2019-04-26 刘西芳 Nematicidal composition containing Imicyafos
CN109588421A (en) * 2018-12-31 2019-04-09 刘西芳 Nematicidal composition containing albendazole
CN109588420A (en) * 2018-12-31 2019-04-09 刘西芳 Nematicidal composition containing 4-Vinyl phenol

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL103644C (en) * 1957-10-25 1900-01-01
US5134133A (en) * 1991-09-30 1992-07-28 Uniroyal Chemical Company, Inc. Oxime phosphate pesticidal compounds, compositions and methods
PT2788343T (en) * 2011-12-11 2018-06-01 Viamet Pharmaceuticals Nc Inc Metalloenzyme inhibitor compounds

Also Published As

Publication number Publication date
CN105348324A (en) 2016-02-24

Similar Documents

Publication Publication Date Title
CN105348324B (en) Organic phosphorus compound and its synthetic method and application containing tetrazolium heterocycle
JP5524328B2 (en) Pyrazolylacrylonitrile compound and use thereof
CA2917264C (en) 4-membered ring carboxamides used as nematicides
JP2614700B2 (en) Novel 2-aminothiazolecarboxamide derivative, method for producing the same, and antibacterial agent for phytopathogenic bacteria
JP6350534B2 (en) Tetrazolinone compounds and uses thereof
Szulczyk et al. Design and synthesis of novel 1H-tetrazol-5-amine based potent antimicrobial agents: DNA topoisomerase IV and gyrase affinity evaluation supported by molecular docking studies
CN104829605A (en) 1-substituted-5-trifluoromethyl-4-pyrazol-1,3,4-oxadiazole thioether or sulfone derivatives and application of derivatives
JP6319317B2 (en) Tetrazolinone compound and use thereof
US4748186A (en) S-trifluorobutenyl derivatives and pesticidal uses thereof
EP0268892A3 (en) Substituted-amido derivatives, method for preparation of the same and phytopathogenic fungicides containing the same
CN108699004A (en) Method for manufacturing carboxylic acid amides
US3974166A (en) Process for the manufacture of bromopyridines
CN106117180B (en) A kind of substituted pyridine connection pyrazoles bishydrazide compounds and its preparation method and application
Patra et al. N-Aryl Modification in γ-Lactam: Design and Synthesis of Novel Monocyclic γ-Lactam Derivatives as Inhibitor for Bacterial Propagation
CN109232552B (en) Piperidine thiazole derivative containing bisamide structure and preparation method and application thereof
CN105924435B (en) A kind of substituted pyrazoles acetamides and its preparation method and application
CN106083929B (en) A kind of tetrazolium phosphate compound and synthetic method with eelworm-killing activity
CN103570642B (en) Isothiazolinone compound and application thereof as bactericide
CN102659714B (en) 5-aryl-1,2,3-thiadiazolyl-4-sulfhydrylacetamide derivatives, and preparation method and application thereof
CN106632129A (en) Disulfide derivative containing 1,3,4-oxa(thia)diazole and preparation method and application of derivative
CN103833638B (en) Phenylpyrazole base acrylonitrile compound and application thereof
CN112624974B (en) Cinnamate compound and application thereof
JP4561068B2 (en) 2-Chloro-1,3-thiazole-5-methanol derivative, process for producing the same and agricultural and horticultural disease control agent
CN106336409B (en) A kind of thiadiazoles -2- thio-ether type compounds and its preparation method and application containing trifluoromethyl pyrazol
CN107108515A (en) A kind of amides compound and its production and use

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
TR01 Transfer of patent right

Effective date of registration: 20171107

Address after: 457000 Henan Puyang economic and Technological Industrial Agglomeration Area

Co-patentee after: He'nan Agricultural University

Patentee after: Puyang Tianjian Biotechnology Co., Ltd.

Address before: 450002 Zhengzhou Cultural Road, Henan, No. 95

Patentee before: He'nan Agricultural University

TR01 Transfer of patent right