CN109438376A - 一种4,5-二杂芳基取代三唑化合物及其制备方法与应用 - Google Patents
一种4,5-二杂芳基取代三唑化合物及其制备方法与应用 Download PDFInfo
- Publication number
- CN109438376A CN109438376A CN201811508254.9A CN201811508254A CN109438376A CN 109438376 A CN109438376 A CN 109438376A CN 201811508254 A CN201811508254 A CN 201811508254A CN 109438376 A CN109438376 A CN 109438376A
- Authority
- CN
- China
- Prior art keywords
- preparation
- compound
- biological carbon
- formula
- alkali
- 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.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- -1 triazole compounds Chemical class 0.000 title claims abstract description 11
- 230000000694 effects Effects 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 28
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 25
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- 239000003513 alkali Substances 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 150000003852 triazoles Chemical class 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 7
- 238000001035 drying Methods 0.000 claims description 7
- 150000003839 salts Chemical class 0.000 claims description 6
- 241000255967 Helicoverpa zea Species 0.000 claims description 5
- 238000010992 reflux Methods 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 4
- 235000011201 Ginkgo Nutrition 0.000 claims description 3
- 241000218628 Ginkgo Species 0.000 claims description 3
- 235000008100 Ginkgo biloba Nutrition 0.000 claims description 3
- 150000008044 alkali metal hydroxides Chemical class 0.000 claims description 3
- 238000003763 carbonization Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- MFGOFGRYDNHJTA-UHFFFAOYSA-N 2-amino-1-(2-fluorophenyl)ethanol Chemical compound NCC(O)C1=CC=CC=C1F MFGOFGRYDNHJTA-UHFFFAOYSA-N 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- HUCVOHYBFXVBRW-UHFFFAOYSA-M caesium hydroxide Inorganic materials [OH-].[Cs+] HUCVOHYBFXVBRW-UHFFFAOYSA-M 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 238000007598 dipping method Methods 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 2
- 239000000463 material Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 238000005406 washing Methods 0.000 claims description 2
- MUIAIUYIYNBLTO-UHFFFAOYSA-N NN.[C] Chemical compound NN.[C] MUIAIUYIYNBLTO-UHFFFAOYSA-N 0.000 claims 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims 1
- 229910052700 potassium Inorganic materials 0.000 claims 1
- 239000011591 potassium Substances 0.000 claims 1
- 241001147381 Helicoverpa armigera Species 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 239000002585 base Substances 0.000 description 13
- 239000000047 product Substances 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 9
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
- YXDXXGXWFJCXEB-UHFFFAOYSA-N 2-furonitrile Chemical compound N#CC1=CC=CO1 YXDXXGXWFJCXEB-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 239000003480 eluent Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- 238000010898 silica gel chromatography Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- UAPNUNDZDVNTDQ-UHFFFAOYSA-N 4,5-diphenyl-1,2,3-triazole Chemical compound C1=CC=CC=C1C1=NNN=C1C1=CC=CC=C1 UAPNUNDZDVNTDQ-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
- 235000002639 sodium chloride Nutrition 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- HJFZUIDQNDCFKZ-UHFFFAOYSA-N 4-(3-bromophenyl)-5-phenyl-2h-triazole Chemical class BrC1=CC=CC(C=2C(=NNN=2)C=2C=CC=CC=2)=C1 HJFZUIDQNDCFKZ-UHFFFAOYSA-N 0.000 description 2
- 240000000233 Melia azedarach Species 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 239000002360 explosive Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 description 1
- LCPVQAHEFVXVKT-UHFFFAOYSA-N 2-(2,4-difluorophenoxy)pyridin-3-amine Chemical compound NC1=CC=CN=C1OC1=CC=C(F)C=C1F LCPVQAHEFVXVKT-UHFFFAOYSA-N 0.000 description 1
- VFAWWVGJVOGUDA-UHFFFAOYSA-N 3-amino-5H-[1,2]oxazolo[4,5-c]quinolin-4-one Chemical compound Nc1noc2c1c(=O)[nH]c1ccccc21 VFAWWVGJVOGUDA-UHFFFAOYSA-N 0.000 description 1
- SUISZCALMBHJQX-UHFFFAOYSA-N 3-bromobenzaldehyde Chemical compound BrC1=CC=CC(C=O)=C1 SUISZCALMBHJQX-UHFFFAOYSA-N 0.000 description 1
- JBOIAPARIKXTEG-UHFFFAOYSA-N 5-phenyl-2h-[1,3]thiazolo[2,3-c][1,2,4]triazole-3-thione Chemical compound N12C(=S)NN=C2SC=C1C1=CC=CC=C1 JBOIAPARIKXTEG-UHFFFAOYSA-N 0.000 description 1
- JCNJHYNMGMMIRL-UHFFFAOYSA-N BrC=1C=C(C=CC1)N1N=C(C=N1)C1=CC=CC=C1 Chemical compound BrC=1C=C(C=CC1)N1N=C(C=N1)C1=CC=CC=C1 JCNJHYNMGMMIRL-UHFFFAOYSA-N 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 150000001540 azides Chemical class 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 125000004799 bromophenyl group Chemical group 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
- JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- CHQMHPLRPQMAMX-UHFFFAOYSA-L sodium persulfate Substances [Na+].[Na+].[O-]S(=O)(=O)OOS([O-])(=O)=O CHQMHPLRPQMAMX-UHFFFAOYSA-L 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- CUPOOAWTRIURFT-UHFFFAOYSA-N thiophene-2-carbonitrile Chemical compound N#CC1=CC=CS1 CUPOOAWTRIURFT-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring 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
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
- A01N43/647—Triazoles; Hydrogenated triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- 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
- Y02A40/22—Improving land use; Improving water use or availability; Controlling erosion
-
- 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
- Y02P60/00—Technologies relating to agriculture, livestock or agroalimentary industries
- Y02P60/20—Reduction of greenhouse gas [GHG] emissions in agriculture, e.g. CO2
- Y02P60/21—Dinitrogen oxide [N2O], e.g. using aquaponics, hydroponics or efficiency measures
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Dentistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Plant Pathology (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Pest Control & Pesticides (AREA)
- Agronomy & Crop Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Abstract
本发明涉及一种4,5‑二杂芳基取代三唑化合物及其制备方法与应用，所述4,5‑二杂芳基取代三唑化合物的结构为
Description
技术领域
本发明属于催化及有机合成领域，具体涉及一种4,5-二杂芳基取代三唑化合物及其制备方法与应用。
背景技术
三唑类结构是生物活性化合物中的一类重要基团，是众多化工、医药中间体的重要结构。三唑类化合物在医药、农药等方面表现出多种生物活性，尤其是在农用杀菌剂方面，目前已商品化的三唑类杀菌剂已有20余种。三唑类化合物的合成方法主要有以下几种：(1)炔烃与叠氮化钠反应制备；(2)苯甲醛、硝基甲烷与叠氮化钠反应制备。上述方法均需用到易爆的叠氮化钠，且反应条件苛刻。因此，急需开发一种不需使用叠氮化钠制备三唑类化合物的方法，本发明提供一种生物碳负载碱催化剂用于催化合成4,5-二杂芳基取代三唑化合物，并测试了4,5-二杂芳基取代三唑化合物的抗虫活性。
发明内容
本发明提供一种式III结构的4,5-二杂芳基取代的三唑类化合物或其药学上可接受的盐，其特征在于式III结构如下：
其中X选自O或S。
本发明的另一实施方案提供上述式III结构化合物的制备方法，其特征在于包括如下步骤：
式I化合物与无水肼，于无水乙醇中回流温度反应3-4小时后，加入式II化合物和生物碳负载碱，继续回流反应4-5小时，即得式III化合物；其中X选自O或S。
式I化合物、无水肼、式II化合物的摩尔比为1:1.3-1.5:1.0-1.2；生物碳负载碱的用量为每毫摩尔式I化合物使用15-20mg生物碳负载碱。
所述生物碳负载碱的制备方法包括如下步骤：
(1)取银杏叶、洗净、干燥至恒重后，在N2存在下，以10℃/min的升温速率升至800℃，保温碳化3小时后，降至室温得生物碳；
(2)将步骤(1)得到的生物碳用碱液浸泡12小时后，水洗、干燥即得生物碳负载碱。
步骤(2)中所述碱液选自碱金属氢氧化物的水溶液，其浓度为4-6mol/L；所述碱金属氢氧化物优选氢氧化钠、氢氧化钾、氢氧化铯中的一种或几种。碱液的用量以能充分浸泡为宜，每克生物碳优选使用10-15mL碱液。
本发明的另一实施方案提供一种4,5-二呋喃-2-基-2H-1,2,3-三唑的制备方法，其特征在于包括如下步骤：
将2-呋喃甲醛溶于无水乙醇中，加入无水肼，加热至回流温度反应3-4小时后，加入2-氰基呋喃和上述生物碳负载碱，继续回流反应4-5小时，即得4,5-二呋喃-2-基-2H-1,2,3-三唑。
2-呋喃甲醛、无水肼、2-氰基呋喃的摩尔比为1:1.3-1.5:1.0-1.2；生物碳负载碱的用量为每毫摩尔式I化合物使用15-20mg生物碳负载碱。
本发明的另一实施方案提供上述式III化合物或其药学上可接受的盐在制备抗虫活性药物中的应用。优选在制备抗棉铃虫药物中的应用。
本发明的另一实施方案提供一种药物组合物，其特征在于以上述式III化合物或其药学上可接受的盐作为有效成分。其还可包括药学上可接受的辅料(例如载体、稀释剂、赋形剂等)。
与现有技术相比，本发明的优点在于：(1)本发明通过获得一种生物碳负载碱，其可用于催化任选取代的苯甲醛(或2-杂芳基甲醛)、无水肼与苯甲腈(或2-氰基呋喃或2-氰基噻吩)合成4,5-二取代的三唑类化合物的催化剂，为三唑类化合物的合成提供了新的思路，避免使用易爆的叠氮化物；(2)本发明制备的4,5-二杂芳基取代三唑化合物在抗棉铃虫方面表现出显著的活性，优于4,5-二苯基取代三唑化合物。
附图说明
图1是产品A的SEM图；
图2是实施例3的HRMS图。
具体实施方式
为了便于对本发明的进一步理解，下面提供的实施例对其做了更详细的说明。但是这些实施例仅供更好的理解发明而并非用来限定本发明的范围或实施原则，本发明的实施方式不限于以下内容。
实施例1生物碳负载碱的制备
(1)取银杏叶(200g)、洗净、干燥至恒重后，在N2存在下，以10℃/min的升温速率升至800℃，保温碳化3小时后，降至室温得生物碳；
(2)取步骤(1)得到的生物碳(10g)用氢氧化钠溶液(6mol/L，100mL)浸泡12小时后，水洗、干燥即得生物碳负载碱(以下简称产品A，图1)。
实施例2
取实施例1步骤(1)得到的生物碳(10g)用氢氧化钾溶液(4mol/L，150mL)浸泡12小时后，水洗、干燥即得生物碳负载碱(以下简称产品B，与图1一致)。
实施例3 4,5-二苯基-2H-1,2,3-三唑的制备
将苯甲醛(2mmol)溶于无水乙醇(20mL)中，加入无水肼(2.4mmol)，加热至回流温度反应6小时后，加入苯甲腈(1.6mmol)和产品A(20mg)，继续回流反应5小时后，过滤回收产品A，滤液浓缩后，用氯仿稀释、并依次用水、饱和氯化钠洗涤，无水硫酸钠干燥，过滤、浓缩，经硅胶柱层析(200-300目硅胶)，用石油醚/乙酸乙酯(15:1-10:1)作为洗脱剂，得到白色固体329mg，即为4,5-二苯基-2H-1,2,3-三唑化合物，收率约92.9％。1H NMR(CDCl3,400MHz),δ:12.82(br s,1H),7.54(d,J＝3.3Hz,4H),7.38-7.36(m,6H).13C NMR(CDCl3,100MHz),δ:142.8,130.4,128.7,128.6,128.3.HRMS(如图2)。
实施例4 4-(3-溴苯基)-5-苯基-2H-1,2,3-三唑的制备
将间溴苯甲醛(1.0mmol)溶于无水乙醇(15mL)中，加入无水肼(1.5mmol)，加热至回流温度反应5小时后，加入苯甲腈(1.0mmol)和产品B(15mg)，继续回流反应4小时后，过滤回收产品B，滤液浓缩后，用氯仿稀释、并依次用水、饱和氯化钠洗涤，无水硫酸钠干燥，过滤、浓缩，经硅胶柱层析(200-300目硅胶)，用石油醚/乙酸乙酯(15:1-10:1)作为洗脱剂，得到固体268mg，即为4-(3-溴苯基)-5-苯基-2H-1,2,3-三唑，收率约89.3％。1H NMR(CDCl3,400MHz),δ:7.76(s,1H),7.55-7.39(m,4H),7.36-7.34(m,3H),7.20-7.17(m,1H).13C NMR(CDCl3,100MHz),δ:132.3,131.6,131.1 130.2,129.2.HRMS Calcd(ESI)m/z forC14H10BrN3:[M+H]+300.0131,found:300.0125,[M+2+H]+302.0111,found:302.0106.
实施例5 4,5-二呋喃-2-基-2H-1,2,3-三唑的制备
将2-呋喃甲醛(2mmol)溶于无水乙醇(20mL)中，加入无水肼(2.6mmol)，加热至回流温度反应4小时后，加入2-氰基呋喃(2.0mmol)和产品A(30mg)，继续回流反应5小时后，过滤回收产品A，滤液浓缩后，用氯仿稀释、并依次用水、饱和氯化钠洗涤，无水硫酸钠干燥，过滤、浓缩，经硅胶柱层析(200-300目硅胶)，用石油醚/乙酸乙酯(10:1-8:1)作为洗脱剂，得到固体336mg，即为4,5-二呋喃-2-基-2H-1,2,3-三唑，收率约83.5％。1H NMR(CDCl3,400MHz),δ:7.45-7.33(m,2H),7.25-7.14(m,4H).13C NMR(CDCl3,100MHz),δ:144.5,142.9,140.6,136.2,128.4.HRMS Calcd(ESI)m/z for C10H7N3O2:[M+H]+202.0611,found:202.0584.
实施例6 4,5-二噻吩-2-基-2H-1,2,3-三唑的制备
将2-噻吩甲醛(1mmol)溶于无水乙醇(15mL)中，加入无水肼(1.5mmol)，加热至回流温度反应3小时后，加入2-氰基噻吩(1.2mmol)和产品B(20mg)，继续回流反应5小时后，过滤回收产品B，滤液浓缩后，用氯仿稀释、并依次用水、饱和氯化钠洗涤，无水硫酸钠干燥，过滤、浓缩，经硅胶柱层析(200-300目硅胶)，用石油醚/乙酸乙酯(10:1-8:1)作为洗脱剂，得到固体192mg，即为4,5-二噻吩-2-基-2H-1,2,3-三唑，收率约82.3％。1H NMR(CDCl3,400MHz),δ:7.29-7.25(m,2H),7.05-6.98(m,4H).13C NMR(CDCl3,100MHz),δ:138.9,131.8,129.5,128.4.HRMS Calcd(ESI)m/z for C10H7N3S2:[M+H]+234.0154,found:234.0147.
实施例7
将2-呋喃甲醛(2mmol)溶于无水乙醇(20mL)中，加入无水肼(2.6mmol)，加热至回流温度反应4小时后，加入2-氰基呋喃(2.0mmol)，继续回流反应5小时后，TLC检测未发现有4,5-二呋喃-2-基-2H-1,2,3-三唑生成。
实施例8
将2-呋喃甲醛(1mmol)溶于无水乙醇(10mL)中，加入无水肼(1.3mmol)，加热至回流温度反应4小时后，加入2-氰基呋喃(1.0mmol)和产品A(实施例5回收的，15mg)，继续回流反应5小时后，过滤回收产品A，滤液浓缩后，用氯仿稀释、并依次用水、饱和氯化钠洗涤，无水硫酸钠干燥，过滤、浓缩，经硅胶柱层析(200-300目硅胶)，用石油醚/乙酸乙酯(10:1-8:1)作为洗脱剂，得到固体163mg，收率约81.1％，结构确证数据与实施例5相同。
实施例9抗棉铃虫活性测试
以木楝素为阳性对照药，测试本发明化合物：4,5-二苯基-2H-1,2,3-三唑、4-(3-溴苯基)-5-苯基-2H-1,2,3-三唑、4,5-二呋喃-2-基-2H-1,2,3-三唑、4,5-二噻吩-2-基-2H-1,2,3-三唑对棉铃虫的抗虫活性。结果如下：
| 测试化合物 | IC<sub>50</sub>(μg/mL) |
| 4,5-二苯基-2H-1,2,3-三唑 | >100 |
| 4-(3-溴苯基)-5-苯基-2H-1,2,3-三唑 | >100 |
| 4,5-二呋喃-2-基-2H-1,2,3-三唑 | 50 |
| 4,5-二噻吩-2-基-2H-1,2,3-三唑 | 50 |
| 木楝素 | 25 |
Claims (10)
1.一种式III结构的4,5-二杂芳基取代的三唑类化合物或其药学上可接受的盐，其特征在于式III结构如下：
其中X选自O或S。
2.权利要求1所述的式III结构化合物的制备方法，其特征在于包括如下步骤：
式I化合物与无水肼，于无水乙醇中回流温度反应3-4小时后，加入式II化合物和生物碳负载碱，继续回流反应4-5小时，即得式III化合物；其中X选自O或S。
3.权利要求2所述的制备方法，其特征在于式I化合物、无水肼、式II化合物的摩尔比为1:1.3-1.5:1.0-1.2；生物碳负载碱的用量为每毫摩尔式I化合物使用15-20mg生物碳负载碱。
4.权利要求2-3任一项所述的制备方法，其特征在于所述生物碳负载碱的制备方法包括如下步骤：
(1)取银杏叶、洗净、干燥至恒重后，在N2存在下，以10℃/min的升温速率升至800℃，保温碳化3小时后，降至室温得生物碳；
(2)将步骤(1)得到的生物碳用碱液浸泡12小时后，水洗、干燥即得生物碳负载碱。
5.权利要求4所述的制备方法，其特征在于步骤(2)中所述碱液选自碱金属氢氧化物的水溶液，其浓度为4-6mol/L。
6.权利要求5所述的制备方法，其特征在于所述碱金属氢氧化物优选氢氧化钠、氢氧化钾、氢氧化铯中的一种或几种。
7.权利要求1所述的式III化合物或其药学上可接受的盐在制备抗虫活性药物中的应用。
8.权利要求7所述的应用，其特征在于优选在制备抗棉铃虫药物中的应用。
9.一种药物组合物，其特征在于以权利要求1所述的式III化合物或其药学上可接受的盐作为有效成分。
10.权利要求9所述的药物组合物，其特征在于其还可包括药学上可接受的辅料(例如载体、稀释剂、赋形剂等)。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811508254.9A CN109438376B (zh) | 2018-12-10 | 2018-12-10 | 一种4,5-二杂芳基取代三唑化合物及其制备方法与应用 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201811508254.9A CN109438376B (zh) | 2018-12-10 | 2018-12-10 | 一种4,5-二杂芳基取代三唑化合物及其制备方法与应用 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109438376A true CN109438376A (zh) | 2019-03-08 |
| CN109438376B CN109438376B (zh) | 2020-09-04 |
Family
ID=65558501
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201811508254.9A Active CN109438376B (zh) | 2018-12-10 | 2018-12-10 | 一种4,5-二杂芳基取代三唑化合物及其制备方法与应用 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109438376B (zh) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101755801A (zh) * | 2010-01-25 | 2010-06-30 | 中国农业大学 | 取代苯基呋喃甲醛缩氨基硫脲类化合物作为昆虫酪氨酸酶抑制剂的用途 |
| CN102246825A (zh) * | 2011-05-11 | 2011-11-23 | 王乃利 | 一种生物农药及其制备方法 |
| CN108794412A (zh) * | 2018-09-10 | 2018-11-13 | 海南师范大学 | 一种4,5-二芳基-2h-1,2,3-三唑化合物的制备方法 |
-
2018
- 2018-12-10 CN CN201811508254.9A patent/CN109438376B/zh active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101755801A (zh) * | 2010-01-25 | 2010-06-30 | 中国农业大学 | 取代苯基呋喃甲醛缩氨基硫脲类化合物作为昆虫酪氨酸酶抑制剂的用途 |
| CN102246825A (zh) * | 2011-05-11 | 2011-11-23 | 王乃利 | 一种生物农药及其制备方法 |
| CN108794412A (zh) * | 2018-09-10 | 2018-11-13 | 海南师范大学 | 一种4,5-二芳基-2h-1,2,3-三唑化合物的制备方法 |
Non-Patent Citations (2)
| Title |
|---|
| SUBHANKAR PANDA ET AL.,: ""Transition Metal, Azide, and Oxidant-Free Homo- and Heterocoupling of Ambiphilic Tosylhydrazones to the Regioselective Triazoles and Pyrazoles"", 《ORG. LETT.》 * |
| 李东风: "《有机化学》", 31 August 2007 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109438376B (zh) | 2020-09-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102796052B (zh) | 具有抗真菌活性的丹皮酚-1,2,3-三氮唑类化合物及其制备方法 | |
| WO2015169096A1 (zh) | 多取代吡啶基吡唑酰胺及其制备方法和用途 | |
| CN106866556A (zh) | 有机叠氮化合物与(Z)‑β‑烯基溴制备1,4‑取代1,2,3‑三氮唑的方法及应用 | |
| US11098049B2 (en) | Synthetic method for benzimidazo[1,2-c]quinazolin-6-ones | |
| Goswami et al. | Sulfonic-acid-functionalized activated carbon made from tea leaves as green catalyst for synthesis of 2-substituted benzimidazole and benzothiazole | |
| CN107129499A (zh) | 含咪唑环的稠杂环类化合物及其制备方法和应用 | |
| CN103641782B (zh) | 一种吡唑酰腙类化合物及其应用 | |
| Zarenezhad et al. | Immobilized [Cu (cdsalMeen)] on silica gel: a highly efficient heterogeneous catalyst for ‘Click’[3+ 2] Huisgen cycloaddition | |
| CN102816150B (zh) | 具有抑菌活性的吲哚及其衍生物-三氮唑类化合物及其制备方法 | |
| JP2023177240A (ja) | ３－トリアゾリルメチル－１，３，５－トリアジン－２，４－ジオン化合物、およびその調製方法と応用 | |
| CN109438376A (zh) | 一种4,5-二杂芳基取代三唑化合物及其制备方法与应用 | |
| CN105541796B (zh) | 一种nh‑1,2,3‑三唑联吡啶化合物的合成方法 | |
| CN105541745B (zh) | 具有杀菌活性的1-(芳氨基乙基)-2-芳基-3,1-苯并恶嗪类化合物及其制备和用途 | |
| CN107935996B (zh) | 一类3,4-二氢嘧啶-2(1h)-(硫)酮类化合物及其制备方法 | |
| CN109433180A (zh) | 一种生物碳负载碱及其作为催化剂的应用 | |
| CN109438375A (zh) | 一种4,5-二苯基取代的三唑类化合物的制备方法 | |
| CN106146418B (zh) | 一种nh-1,2,3-三唑化合物的合成方法 | |
| CN105566235A (zh) | 利用铝盐催化分步合成nh-1,2,3-三唑的方法 | |
| CN107266442A (zh) | 具有抗肿瘤活性的哌啶并吡啶类化合物的制备方法 | |
| CN106699656B (zh) | 培氟沙星醛缩4-芳基氨基硫脲类衍生物及其制备方法和应用 | |
| CN107151248A (zh) | 具有生物活性的哌啶磺酰胺类化合物的制备方法 | |
| Skinner et al. | Synthesis and Biological Activity of Some 6-(Substituted)-aminopurines | |
| CN102924383A (zh) | 一种2-硫代乙内酰脲及其制备方法和应用 | |
| CN109232543A (zh) | 一种杀菌剂及其应用 | |
| CN112830926B (zh) | 一种n-乙酰基莫西沙星的丙烯酮衍生物及其制备方法和应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |