CN115197261B - Synthesis method of oxadiazine boron derivative - Google Patents
Synthesis method of oxadiazine boron derivative Download PDFInfo
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- CN115197261B CN115197261B CN202211056270.5A CN202211056270A CN115197261B CN 115197261 B CN115197261 B CN 115197261B CN 202211056270 A CN202211056270 A CN 202211056270A CN 115197261 B CN115197261 B CN 115197261B
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- -1 oxadiazine boron derivative Chemical class 0.000 title claims abstract description 9
- 238000001308 synthesis method Methods 0.000 title description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 54
- 238000006243 chemical reaction Methods 0.000 claims abstract description 23
- 238000000034 method Methods 0.000 claims abstract description 13
- 238000001914 filtration Methods 0.000 claims abstract description 7
- 230000035484 reaction time Effects 0.000 claims abstract description 7
- 238000005406 washing Methods 0.000 claims abstract description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical class OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- 239000003208 petroleum Substances 0.000 claims description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- 239000007810 chemical reaction solvent Substances 0.000 claims description 3
- 239000012046 mixed solvent Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- 238000003756 stirring Methods 0.000 claims description 2
- 229940125904 compound 1 Drugs 0.000 claims 2
- 229940125782 compound 2 Drugs 0.000 claims 2
- 230000001376 precipitating effect Effects 0.000 claims 1
- 239000003054 catalyst Substances 0.000 abstract description 6
- 239000000758 substrate Substances 0.000 abstract description 6
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 abstract description 3
- 239000004327 boric acid Substances 0.000 abstract description 3
- 230000002194 synthesizing effect Effects 0.000 abstract description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 33
- 239000007787 solid Substances 0.000 description 16
- SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical group 0.000 description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000012024 dehydrating agents Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 150000002431 hydrogen Chemical group 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- UBRFUPVMYXDNHD-UHFFFAOYSA-N oxadiazaborole Chemical class O1N=NB=C1 UBRFUPVMYXDNHD-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- MNIPVWXWSPXERA-IDNZQHFXSA-N (6r,7r)-1-[(4s,5r)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-4,7-dihydroxy-6-(11-phenoxyundecanoyloxy)-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid Chemical compound C([C@@H](C)[C@H](OC(C)=O)C(=C)CCC12[C@@H]([C@@H](OC(=O)CCCCCCCCCCOC=3C=CC=CC=3)C(O1)(C(O)=O)C(O)(C(O2)C(O)=O)C(O)=O)O)C1=CC=CC=C1 MNIPVWXWSPXERA-IDNZQHFXSA-N 0.000 description 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229940126650 Compound 3f Drugs 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 238000004617 QSAR study Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- LXGQHDUCNDGTDB-PAMNCVQHSA-N [2-[(8s,9r,10s,13s,14s,16s,17r)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl] acetate;[2-[(8s,9r,10s,13s,14s,16s,17r)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11, Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(C)=O)(O)[C@@]1(C)CC2O.C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COP(O)(O)=O)(O)[C@@]1(C)CC2O LXGQHDUCNDGTDB-PAMNCVQHSA-N 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000005620 boronic acid group Chemical class 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- COCAUCFPFHUGAA-MGNBDDOMSA-N n-[3-[(1s,7s)-5-amino-4-thia-6-azabicyclo[5.1.0]oct-5-en-7-yl]-4-fluorophenyl]-5-chloropyridine-2-carboxamide Chemical compound C=1C=C(F)C([C@@]23N=C(SCC[C@@H]2C3)N)=CC=1NC(=O)C1=CC=C(Cl)C=N1 COCAUCFPFHUGAA-MGNBDDOMSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
本发明提供一种噁二氮杂硼衍生物的合成方法，在乙酸乙酯中使用硼酸、胺肟合成制得，反应在无催化剂和温和条件下进行，且所有产品均可通过过滤和洗涤快速纯化。本发明方法的优点包括无催化剂、反应时间短、易于后处理，以及它们能够适应广泛的底物，以及良好的产率。The invention provides a method for synthesizing oxadiazaboryl derivatives, which are synthesized by using boric acid and amine oxime in ethyl acetate, the reaction is carried out without a catalyst and under mild conditions, and all products can be quickly purified by filtering and washing. The advantages of the method of the invention include no catalyst, short reaction time, easy post-treatment, and they can adapt to a wide range of substrates, as well as good yield.
Description
本申请要求2022年07月06日提交的中国专利申请2022107908290的优先权，所述申请的内容均援引加入本文。This application claims priority to Chinese patent application No. 2022107908290 filed on July 6, 2022, the contents of which are incorporated herein by reference.
技术领域Technical Field
本发明属于药物开发技术领域，具体涉及噁二氮杂硼及其合成方法和用途。The invention belongs to the technical field of drug development, and specifically relates to oxadiazaborane and a synthesis method and application thereof.
背景技术Background technique
研究发现，噁二氮杂硼类化合物具有较强的杀菌作用(Pir,M.,Agirbas,H.,Budak,F.et al.Synthesis,characterization,antimicrobial activity,and QSARstudies on substituted oxadiazaboroles.Med Chem Res 25,1794–1812(2016).)Studies have found that oxadiazaborole compounds have strong bactericidal effects (Pir, M., Agirbas, H., Budak, F. et al. Synthesis, characterization, antimicrobial activity, and QSAR studies on substituted oxadiazaboroles. Med Chem Res 25, 1794–1812 (2016).)
然而其制备方法需要高温反应，且反应时间长，不利于工业化生产。因此，有必要开发一种操作更安全且工艺时间短的方法来制备噁二氮杂硼类化合物。However, the preparation method thereof requires high temperature reaction and long reaction time, which is not conducive to industrial production. Therefore, it is necessary to develop a method for preparing oxadiazine boron compounds with safer operation and shorter process time.
发明内容Summary of the invention
第一方面，本发明提供一类噁二氮杂硼化合物。In a first aspect, the present invention provides a class of oxadiazaboron compounds.
一类噁二氮杂硼化合物，结构式如下：A class of oxadiazaboron compounds, the structural formula is as follows:
其中，R’为各自独立的氢，C1-C6的烷基或C1-C6的烷氧基，卤素、一个或多个卤素取代的甲基、苯基、硝基。Wherein, R' is independently hydrogen, C 1 -C 6 alkyl or C 1 -C 6 alkoxy, halogen, methyl substituted with one or more halogens, phenyl, or nitro.
R为各自独立的氢，C1-C6的烷基或C1-C6的烷氧基，卤素、一个或多个卤素取代的甲基、苯基、硝基。R is independently hydrogen, C 1 -C 6 alkyl or C 1 -C 6 alkoxy, halogen, methyl substituted with one or more halogens, phenyl, or nitro.
所述C1-C6烷基是指甲基、乙基、丙基、异丙基、正丁基、异丁基、仲丁基、叔丁基、正戊基、异戊基、新戊基、正己基或异己基；所述C1-C6的烷氧基是指甲氧基或乙氧基；所述卤素是氟、氯、溴或碘。The C 1 -C 6 alkyl group refers to methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl or isohexyl; the C 1 -C 6 alkoxy group refers to methoxy or ethoxy; the halogen group refers to fluorine, chlorine, bromine or iodine.
R’可以独立的为邻位、间位或对位，可以邻位、间位和对位同时取代，也可以单独取代。R' can independently be at the ortho, meta or para position, and can be substituted at the ortho, meta and para positions simultaneously or individually.
R可以独立的为邻位、间位或对位，可以邻位、间位和对位同时取代，也可以单独取代。R may independently be at the ortho, meta or para position, and may be substituted at the ortho, meta and para positions simultaneously or individually.
所述式3化合物选自3a-3k化合物:The compound of formula 3 is selected from compounds 3a-3k:
第二方面，本发明提供上述式3化合物的制备方法。In a second aspect, the present invention provides a method for preparing the compound of formula 3.
上述式3化合物合成路线如下：The synthetic route of the compound of formula 3 is as follows:
反应溶剂选自四氢呋喃、甲醇、乙腈、N,N-二甲基甲酰胺、丙酮、乙酸乙酯中的一种或几种混合，优选乙酸乙酯。The reaction solvent is selected from tetrahydrofuran, methanol, acetonitrile, N,N-dimethylformamide, acetone, ethyl acetate or a mixture thereof, preferably ethyl acetate.
本发明反应温度为室温，反应时间为5min。The reaction temperature of the present invention is room temperature, and the reaction time is 5 minutes.
进一步，本发明操作步骤为：在圆底烧瓶中将胺肟1、苯基硼酸2衍生物和乙酸乙酯混合在一起，并在室温下搅拌5分钟，当反应完成时将石油醚加入圆底烧瓶中，产物立即从反应体系中沉淀出来，过滤，用乙酸乙酯和石油醚混合溶剂洗涤，得纯品。Furthermore, the operation steps of the present invention are: mixing amine oxime 1, phenylboronic acid 2 derivative and ethyl acetate in a round-bottom flask and stirring at room temperature for 5 minutes. When the reaction is completed, petroleum ether is added to the round-bottom flask, and the product is immediately precipitated from the reaction system, filtered, and washed with a mixed solvent of ethyl acetate and petroleum ether to obtain a pure product.
有益效果：Beneficial effects:
本发明提供一种噁二氮杂硼衍生物的合成方法，在乙酸乙酯中使用硼酸、胺肟合成制得，反应在无催化剂和温和条件下进行，且所有产品均可通过过滤和洗涤快速纯化。本发明方法的优点包括无催化剂、反应时间短、易于后处理，以及它们能够适应广泛的底物，以及良好的产率。此外，通过简单的过滤和洗涤，可以方便地纯化产品。The invention provides a method for synthesizing oxadiazaboryl derivatives, which are synthesized by using boric acid and amine oxime in ethyl acetate, the reaction is carried out without a catalyst and under mild conditions, and all products can be quickly purified by filtering and washing. The advantages of the method of the invention include no catalyst, short reaction time, easy post-treatment, and they can adapt to a wide range of substrates, as well as good yields. In addition, the product can be easily purified by simple filtering and washing.
具体实施方式：Detailed ways:
下面通过具体实施例对本发明进行具体描述，在此指出以下实施例只用于对本发明进行进一步说明，不能理解为对本发明保护范围的限制，本领域的技术熟练人员可以根据上述发明内容对本发明作出一些非本质的改进和调整。The present invention is described in detail below through specific embodiments. It is pointed out that the following embodiments are only used to further illustrate the present invention and cannot be understood as limiting the scope of protection of the present invention. Those skilled in the art can make some non-essential improvements and adjustments to the present invention based on the above invention content.
实施例Example
原料制备方法：Raw material preparation method:
向圆底烧瓶中加入苄腈(19.4mmol，1.0equiv)、盐酸羟胺(29.1mmol，1.5equiv)、三乙胺(29.1mmol，1.5equiv)和乙醇(15mL)。将所得混合物在回流下加热至70℃并保持5小时。当反应完成时，将温度降低至25℃，然后减压除去溶剂并加入饱和NaCl溶液(25mL)。随后，水相用乙酸乙酯(4×20mL)萃取，用无水Na2SO4干燥，加入硅胶真空浓缩。残余物经柱层析(石油醚/乙酸乙酯4:1)纯化得到目标产物1。Benzonitrile (19.4 mmol, 1.0 equiv), hydroxylamine hydrochloride (29.1 mmol, 1.5 equiv), triethylamine (29.1 mmol, 1.5 equiv) and ethanol (15 mL) were added to a round-bottom flask. The resulting mixture was heated to 70 °C under reflux for 5 hours. When the reaction was complete, the temperature was lowered to 25 °C, and then the solvent was removed under reduced pressure and saturated NaCl solution (25 mL) was added. Subsequently, the aqueous phase was extracted with ethyl acetate (4×20 mL), dried over anhydrous Na 2 SO 4 , and concentrated in vacuo by adding silica gel. The residue was purified by column chromatography (petroleum ether/ethyl acetate 4:1) to obtain the desired product 1.
在圆底烧瓶中将胺肟1(1.1mmol，1.0equiv)、苯基硼酸2(1.1mmol，1.0equiv)衍生物和乙酸乙酯(2mL)混合在一起并在室温下搅拌5分钟。用TLC监测反应进程。当反应完成时，将过量的石油醚(5mL)加入圆底烧瓶中，产物立即从反应体系中沉淀出来。过滤，用乙酸乙酯和石油醚(15：1)混合溶剂洗涤，得纯品。In a round-bottom flask, amine oxime 1 (1.1 mmol, 1.0 equiv), phenylboronic acid 2 (1.1 mmol, 1.0 equiv) derivative and ethyl acetate (2 mL) were mixed together and stirred at room temperature for 5 minutes. The reaction progress was monitored by TLC. When the reaction was completed, an excess of petroleum ether (5 mL) was added to the round-bottom flask, and the product immediately precipitated from the reaction system. Filter and wash with a mixed solvent of ethyl acetate and petroleum ether (15:1) to obtain the pure product.
结果与讨论Results and discussion
在初步试验中，胺肟1a和苯基硼酸2a溶解在四氢呋喃(THF)中，并在室温下将脱水剂TiCl4滴加到混合体系中。1小时后，通过薄层色谱(TLC)分析反应，但未检测到所需产物，可能是由于起始材料和TiCl4之间形成了盐(表1，条目1)。然后，发明人在不添加任何脱水剂的情况下在室温下再次测试。令人惊讶的是，当起始材料溶解在THF中时，反应迅速发生，产率约为85％(条目2)。随后，发明人将反应时间延长至1小时，但产物的收率没有显着差异(条目3)。此外，偕胺肟和苯基硼酸在各种溶剂中进行了研究，包括甲醇、乙醇、乙腈、乙酸乙酯等(条目4-9)。最后发现室温下乙酸乙酯中收率最高，且产物仅仅经过简单的过滤和洗涤即可得到高纯度目标产物。In preliminary experiments, amidoxime 1a and phenylboronic acid 2a were dissolved in tetrahydrofuran (THF), and dehydrating agent TiCl 4 was added dropwise to the mixed system at room temperature. After 1 hour, the reaction was analyzed by thin layer chromatography (TLC), but no desired product was detected, probably due to the formation of salt between the starting material and TiCl 4 (Table 1, entry 1). Then, the inventors tested again at room temperature without adding any dehydrating agent. Surprisingly, when the starting material was dissolved in THF, the reaction occurred rapidly with a yield of about 85% (entry 2). Subsequently, the inventors extended the reaction time to 1 hour, but there was no significant difference in the yield of the product (entry 3). In addition, amidoxime and phenylboronic acid were studied in various solvents, including methanol, ethanol, acetonitrile, ethyl acetate, etc. (entries 4-9). Finally, it was found that the yield was highest in ethyl acetate at room temperature, and the product was obtained with high purity after only simple filtration and washing.
表1.反应条件的优化Table 1. Optimization of reaction conditions
a反应条件：1a(1.1mmol，1.0equiv)、2a(1.1mmol，1.0equiv)和乙酸乙酯(2.0mL)。b添加脱水剂TiCl4(10mol％)。c分离产量。d没有反应。 a Reaction conditions: 1a (1.1 mmol, 1.0 equiv), 2a (1.1 mmol, 1.0 equiv) and ethyl acetate (2.0 mL). b Addition of dehydrating agent TiCl 4 (10 mol%). c Isolated yield. d No reaction.
在优化的条件下，发明人探索了取代偕胺肟和苯基硼酸之间底物反应的范围和一般性。如表2所示，多种硼酸和偕胺肟与该反应兼容。苯环上的给电子基团(如-Me、-Ph)、卤素基团(F和I)和吸电子基团都具有良好的耐受性，并且所需的产物以良好至优异的产率(表2,3a–3e,3g–3k,82–93％)。然而，当苯环带有羟基时，没有检测到产物3l。此外，2,6-二甲基苯基硼酸作为底物参与了反应。化合物3f(75％)的收率下降。Under optimized conditions, the inventors explored the scope and generality of the substrate reaction between substituted amidoximes and phenylboronic acid. As shown in Table 2, a variety of boronic acids and amidoximes are compatible with the reaction. Electron-donating groups (such as -Me, -Ph), halogen groups (F and I), and electron-withdrawing groups on the benzene ring are well tolerated, and the desired products are obtained in good to excellent yields (Table 2, 3a–3e, 3g–3k, 82–93%). However, when the benzene ring carries a hydroxyl group, no product 3l is detected. In addition, 2,6-dimethylphenylboronic acid participated in the reaction as a substrate. The yield of compound 3f (75%) decreased.
表2.噁二氮杂硼3合成的底物范围Table 2. Substrate scope of the synthesis of oxadiazaborane 3
综上所述，本发明提供一种噁二氮杂硼衍生物的合成方法，在乙酸乙酯中使用硼酸、胺肟合成制得，反应在无催化剂和温和条件下进行，且所有产品均可通过过滤和洗涤快速纯化。本发明方法的优点包括无催化剂、反应时间短、易于后处理，以及它们能够适应广泛的底物，以及良好的产率。此外，通过简单的过滤和洗涤，可以方便地纯化产品。In summary, the present invention provides a method for synthesizing oxadiazaboryl derivatives, which are synthesized using boric acid and amine oxime in ethyl acetate, the reaction is carried out without a catalyst and under mild conditions, and all products can be quickly purified by filtering and washing. The advantages of the method of the present invention include no catalyst, short reaction time, easy post-treatment, and they can adapt to a wide range of substrates, as well as good yields. In addition, the product can be easily purified by simple filtration and washing.
实验数据：Experimental data:
Amidoxime(1a)1.White solid(2.20g,85％yield),PE/EA＝4:1,mp 67-69℃.1HNMR(600MHz,DMSO-d6):δ9.63(1H,s),7.69–7.67(2H,m),7.38–7.36(3H,m),5.80(2H,s).13CNMR(151MHz,DMSO-d6):δ151.29,133.84,129.33,128.56,125.85.Amidoxime (1a) 1 . White solid (2.20 g, 85% yield), PE/EA=4:1, mp 67-69°C. 1 HNMR (600 MHz, DMSO-d 6 ): δ9.63 (1H, s), 7.69–7.67 (2H, m), 7.38–7.36 (3H, m), 5.80 (2H, s). 13 CNMR (151 MHz, DMSO-d 6 ): δ151.29, 133.84, 129.33, 128.56, 125.85.
Amidoxime(1b)2.White solid(2.20g,87％yield),PE/EA＝4:1,mp 124-127℃.1HNMR(600MHz,DMSO-d6)δ9.52(1H,s),7.56(2H,d,J8.2),7.17(2H,d,J8.0),5.73(1H,s),2.31(3H,s).13C NMR(151MHz,DMSO-d6)δ151.24,138.71,131.03,129.10,125.74,21.28.Amidoxime (1b) 2 . White solid (2.20 g, 87% yield), PE/EA=4:1, mp 124-127°C. 1 H NMR (600 MHz, DMSO-d 6 ) δ9.52 (1H, s), 7.56 (2H, d, J8.2), 7.17 (2H, d, J8.0), 5.73 (1H, s), 2.31 (3H, s). 13 C NMR (151 MHz, DMSO-d 6 ) δ151.24, 138.71, 131.03, 129.10, 125.74, 21.28.
Amidoxime(1c)2.White solid(2.20g,90％yield),PE/EA＝4:1,mp 107-110℃.1HNMR(600MHz,DMSO-d6)δ9.44(1H,s),7.61(2H,d,J8.9),6.92(2H,d,J8.9),5.71(2H,s),3.77(3H,s).13C NMR(151MHz,DMSO-d6)δ160.27,151.05,127.17,126.24,113.91,55.61.Amidoxime (1c) 2 . White solid (2.20 g, 90% yield), PE/EA=4:1, mp 107-110°C. 1 H NMR (600 MHz, DMSO-d 6 ) δ9.44 (1H, s), 7.61 (2H, d, J8.9), 6.92 (2H, d, J8.9), 5.71 (2H, s), 3.77 (3H, s). 13 C NMR (151 MHz, DMSO-d 6 ) δ160.27, 151.05, 127.17, 126.24, 113.91, 55.61.
Amidoxime(1d)3.White solid(2.00g,87％yield),PE/EA＝4:1,mp 157-160℃.1HNMR(600MHz,DMSO-d6)δ9.71(1H,s),7.74(2H,d,J8.3),7.47(2H,d,J8.1),5.83(2H,s).13CNMR(151MHz,DMSO-d6)δ150.61,137.36,133.38,127.90,95.70.Amidoxime (1d) 3 . White solid (2.00 g, 87% yield), PE/EA=4:1, mp 157-160°C. 1 HNMR (600 MHz, DMSO-d 6 ) δ9.71 (1H, s), 7.74 (2H, d, J8.3), 7.47 (2H, d, J8.1), 5.83 (2H, s). 13 CNMR (151 MHz, DMSO-d 6 ) δ150.61, 137.36, 133.38, 127.90, 95.70.
Amidoxime(1e)3.White solid(2.20g,85％yield),PE/EA＝4:1,mp 79-81℃.1HNMR(600MHz,DMSO-d6)δ9.63(1H,s),7.73–7.70(2H,m),7.20(2H,t,J8.9),5.83(2H,s).13CNMR(151MHz,DMSO-d6)δ163.79,162.16,150.52,130.31,130.29,128.02,127.96,115.49,115.34.Amidoxime (1e) 3 . White solid (2.20 g, 85% yield), PE/EA = 4:1, mp 79-81°C. 1 HNMR (600 MHz, DMSO-d 6 ) δ 9.63 (1H, s), 7.73–7.70 (2H, m), 7.20 (2H, t, J 8.9), 5.83 (2H, s). 13 CNMR (151 MHz, DMSO-d 6 ) δ 163.79, 162.16, 150.52, 130.31, 130.29, 128.02, 127.96, 115.49, 115.34.
3,5-diphenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3a)4.White solid(0.22g,92％yield)；mp 158-160℃.1H NMR(600MHz,DMSO-d6)δ10.46(1H,s),8.00(2H,dd,J6.5,3.2),7.96(2H,d,J6.5),7.59(3H,dd,J 7.0,3.8),7.55(1H,d,J7.2),7.52(2H,t,J7.1).13C NMR(151MHz,DMSO-d6)δ159.75,134.38,131.59,131.24,129.45,128.73,127.20,126.78.11B NMR(193MHz,DMSO-d6)δ32.07.3,5-diphenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3a) 4 .White solid(0.22g,92％yield);mp 158-160℃. 1 H NMR(600MHz,DMSO-d 6 )δ10.46(1H,s),8.00(2H,dd,J6.5,3.2),7.96(2H,d,J6.5),7.59(3H,dd,J 7.0,3.8),7.55(1H,d,J7.2),7.52(2H,t,J7.1). 13 C NMR(151MHz,DMSO-d 6 )δ159.75,134.38,131.59,131.24,129.45,128.73,127.20,126.78. 11 B NMR (193 MHz, DMSO-d 6 )δ32.07.
3-phenyl-5-(p-tolyl)-4,5-dihydro-1,2,4,5-oxadiazaborole(3b)4.Whitesolid(0.22g,85％yield)；mp 143-146℃.1H NMR(600MHz,DMSO-d6)δ10.36(1H,s),7.98–7.95(2H,m),7.83(2H,d,J 7.9),7.58–7.53(4H,m),7.32(2H,d,J 7.5),2.37(4H,s).13CNMR(151MHz,DMSO-d6)δ159.66,141.31,134.42,131.22,129.45,129.41,127.22,126.74,21.77.11B NMR(193MHz,DMSO-d6)δ33.74.3-phenyl-5-(p-tolyl)-4,5-dihydro-1,2,4,5-oxadiazaborole(3b) 4 .White solid (0.22 g, 85% yield); mp 143-146°C. 1 H NMR (600 MHz, DMSO-d 6 ) δ 10.36 (1H, s), 7.98–7.95 (2H, m), 7.83 (2H, d, J 7.9), 7.58–7.53 (4H, m), 7.32 (2H, d, J 7.5), 2.37 (4H, s). 13 CNMR (151 MHz, DMSO-d 6 )δ159.66,141.31,134.42,131.22,129.45,129.41,127.22,126.74,21.77. 11 B NMR (193 MHz, DMSO-d 6 )δ33.74.
5-(4-ethylphenyl)-3-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3c).White solid(0.23g,82％yield)；mp 116-119℃.1H NMR(600MHz,DMSO-d6)δ10.37(1H,s),7.97(2H,dd,J 6.6,2.9),7.86(2H,d,J 7.8),7.58–7.57(3H,m),7.35(2H,d,J7.8),2.67(2H,q,J 7.6),1.22(4H,t,J 7.6).13C NMR(151MHz,DMSO-d6)δ159.67,147.51,134.51,131.22,129.44,128.22,127.23,126.75,28.83,15.80.11B NMR(193MHz,DMSO-d6)δ32.86.HRMS(ESI):m/z[M+H]+calculated for C15H16BN2O:251.1350,found:251.1344.5-(4-ethylphenyl)-3-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3c).White solid(0.23g,82％yield);mp 116-119℃. 1 H NMR(600MHz,DMSO-d 6 )δ10.37(1H,s),7.97(2H,dd,J 6.6,2.9),7.86(2H,d,J 7.8),7.58–7.57(3H,m),7.35(2H,d,J 7.8),2.67(2H,q,J 7.6),1.22(4H,t,J 7.6). 13 C NMR(151MHz,DMSO-d 6 )δ159.67,147.51,134.51,131.22,129.44,128.22,127.23,126.75,28.83,15.80. 11 B NMR (193 MHz, DMSO-d 6 )δ32.86. HRMS (ESI): m/z [M+H] + calculated for C 15 H 16 BN 2 O: 251.1350, found: 251.1344.
5-(4-fluorophenyl)-3-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3d).White solid(0.24g,90％yield)；mp 192-194℃.1H NMR(600MHz,DMSO-d6)δ10.46(1H,s),8.03–8.00(2H,m),7.99–7.97(2H,m),7.60–7.58(3H,m),7.36(2H,t,J8.9).13C NMR(151MHz,DMSO-d6)δ165.49,163.84,159.75,136.91,136.85,131.27,129.46,127.12,126.74,115.99,115.86.11B NMR(193MHz,DMSO-d6)δ33.62.HRMS(ESI):m/z[M+H]+calculated for C13H11BN2OF:241.0943,found:241.0939.5-(4-fluorophenyl)-3-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3d).White solid(0.24g,90％yield);mp 192-194℃. 1 H NMR(600MHz,DMSO-d 6 )δ10.46(1H,s),8.03–8.00(2H,m),7.99–7.97(2H,m),7.60–7.58(3H,m),7.36(2H,t,J8.9). 13 C NMR(151MHz,DMSO-d 6 )δ165.49,163.84,159.75,136.91,136.85,131.27,129.46,127.12,126.74,115.99,115.86. 11 B NMR (193 MHz, DMSO-d 6 )δ33.62. HRMS (ESI): m/z [M+H] + calculated for C 13 H 11 BN 2 OF: 241.0943, found: 241.0939.
5-(4-nitrophenyl)-3-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3e)4.White solid(0.27g,93％yield)；mp 254-256℃,1H NMR(600MHz,DMSO-d6)δ10.71(1H,s),8.35(2H,d,J8.5),8.18(2H,d,J8.5),7.97(2H,dd,J6.4,2.9),7.61–7.57(3H,m).13CNMR(151MHz,DMSO-d6)δ159.96,149.60,135.57,131.40,129.49,126.87,126.75,123.43.11B NMR(193MHz,DMSO-d6)δ34.03.5-(4-nitrophenyl)-3-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3e) 4 .White solid(0.27g,93％yield);mp 254-256℃, 1 H NMR(600MHz,DMSO-d 6 )δ10.71(1H,s),8.35(2H,d,J8.5),8.18(2H,d,J8.5),7.97(2H,dd,J6.4,2.9),7.61–7.57(3H,m). 13 CNMR(151MHz,DMSO-d 6 )δ159.96,149.60,135.57,131.40,129.49,126.87,126.75,123.43. 11 B NMR (193 MHz, DMSO-d 6 ) δ 34.03.
5-(2,6-dimethylphenyl)-3-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3f).White solid(0.21g,80％yield)；mp 148-151℃,1H NMR(600MHz,DMSO-d6)δ10.26(1H,s),7.95(3H,dd,J6.6,3.0),7.58–7.53(4H,m),7.25(2H,t,J7.6),7.07(3H,d,J 7.6),2.31(9H,s).13C NMR(151MHz,DMSO-d6)δ159.34,141.91,131.25,130.05,129.48,127.10,126.89,126.72,22.89.11B NMR(193MHz,DMSO-d6)δ33.97.HRMS(ESI):m/z[M+H]+calculated for C15H16BN2O:251.1350,found:251.1345.5-(2,6-dimethylphenyl)-3-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3f).White solid(0.21g,80％yield);mp 148-151℃, 1 H NMR(600MHz,DMSO-d 6 )δ10.26(1H,s),7.95(3H,dd,J 6.6,3.0),7.58–7.53(4H,m),7.25(2H,t,J 7.6),7.07(3H,d,J 7.6),2.31(9H,s). 13 C NMR(151MHz,DMSO-d 6 )δ159.34,141.91,131.25,130.05,129.48,127.10,126.89,126.72,22.89. 11 B NMR (193 MHz, DMSO-d 6 )δ33.97. HRMS (ESI): m/z [M+H] + calculated for C 15 H 16 BN 2 O: 251.1350, found: 251.1345.
5-(naphthalen-1-yl)-3-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3g).White solid(0.25g,84％yield)；mp 134-136℃,1H NMR(600MHz,DMSO-d6)δ10.58(1H,s),8.66(1H,d,J 8.4),8.23(1H,d,J 6.8),8.12(1H,d,J 8.1),8.06(3H,d,J 4.6),8.01(1H,d,J 8.1),7.67(3H,dd,J 13.0,6.3),7.60(5H,t,J 6.2).13C NMR(151MHz,DMSO-d6)δ159.70,136.00,135.73,133.44,131.80,131.32,129.47,129.08,128.37,127.34,127.13,126.97,126.46,125.81.11B NMR(193MHz,DMSO-d6)δ34.99.HRMS(ESI):m/z[M+H]+calculated for C17H14BN2O:273.1193,found:273.1196.5-(naphthalen-1-yl)-3-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3g).White solid(0.25g,84％yield);mp 134-136℃, 1H NMR(600MHz,DMSO-d 6 )δ10.58(1H,s),8.66(1H,d,J 8.4),8.23(1H,d,J 6.8),8.12(1H,d,J 8.1),8.06(3H,d,J 4.6),8.01(1H,d,J 8.1),7.67(3H,dd,J 13.0,6.3),7.60(5H,t,J 6.2). 13C NMR(151MHz,DMSO-d 6 )δ159.70,136.00,135.73,133.44,131.80,131.32,129.47,129.08,128.37,127.34,127.13,126.97,126.46,125.81. 11 B NMR (193 MHz, DMSO-d 6 )δ34.99. HRMS (ESI): m/z [M+H] + calculated for C 17 H 14 BN 2 O: 273.1193, found: 273.1196.
3-(4-methoxyphenyl)-5-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3h)5.White solid(0.21g,92％yield)；mp 176-179℃,1H NMR(600MHz,DMSO-d6)δ10.33(1H,s),7.94(5H,t,J 7.4),7.55(1H,t,J 7.2),7.51(2H,t,J 7.2),7.13(3H,d,J 8.7),3.85(4H,s).13C NMR(151MHz,DMSO-d6)δ161.60,159.41,134.35,131.52,128.71,128.34,119.46,114.85,55.82.11B NMR(193MHz,DMSO-d6)δ33.27.3-(4-methoxyphenyl)-5-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3h) 5 .White solid(0.21g,92％yield);mp 176-179℃, 1 H NMR(600MHz,DMSO-d 6 )δ10.33(1H,s),7.94(5H,t,J 7.4),7.55(1H,t,J 7.2),7.51(2H,t,J 7.2),7.13(3H,d,J 8.7),3.85(4H,s). 13 C NMR(151MHz,DMSO-d 6 )δ161.60,159.41,134.35,131.52,128.71,128.34,119.46,114.85,55.82. 11 B NMR (193 MHz, DMSO-d 6 )δ33.27.
5-phenyl-3-(p-tolyl)-4,5-dihydro-1,2,4,5-oxadiazaborole(3i)5.Whitesolid(0.21g,90％yield)；mp 151-154℃,1H NMR(600MHz,DMSO-d6)δ10.37(1H,s),7.94(2H,d,J6.7),7.87(2H,d,J 8.1),7.55(1H,t,J 7.3),7.51(2H,t,J 7.2),7.38(2H,d,J8.0),2.39(3H,s).13C NMR(151MHz,DMSO-d6)δ159.67,141.05,134.36,131.55,129.99,128.72,126.67,124.38,21.46.11B NMR(193MHz,DMSO-d6)δ33.27.5-phenyl-3-(p-tolyl)-4,5-dihydro-1,2,4,5-oxadiazaborole(3i) 5 .White solid (0.21 g, 90% yield); mp 151-154°C, 1 H NMR (600 MHz, DMSO-d 6 )δ10.37(1H, s),7.94(2H, d, J 6.7),7.87(2H, d, J 8.1),7.55(1H, t, J 7.3),7.51(2H, t, J 7.2),7.38(2H, d, J 8.0),2.39(3H, s). 13 C NMR(151 MHz, DMSO-d 6 )δ159.67,141.05,134.36,131.55,129.99,128.72,126.67,124.38,21.46. 11 B NMR (193 MHz, DMSO-d 6 )δ33.27.
3-(4-iodophenyl)-5-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3j)5.White solid(0.16g,83％yield)；mp 219-221℃,1H NMR(600MHz,DMSO-d6)δ10.49(1H,s),7.97(2H,d,J 8.4),7.92(2H,d,J 6.7),7.76(2H,d,J 7.9),7.55(1H,t,J 7.3),7.50(2H,t,J 7.1).13C NMR(151MHz,DMSO-d6)δ159.22,138.35,134.36,131.67,128.76,128.56,126.63,98.39.11B NMR(193MHz,DMSO-d6)δ33.67.3-(4-iodophenyl)-5-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3j) 5 .White solid(0.16g,83％yield);mp 219-221℃, 1 H NMR(600MHz,DMSO-d 6 )δ10.49(1H,s),7.97(2H,d,J 8.4),7.92(2H,d,J 6.7),7.76(2H,d,J 7.9),7.55(1H,t,J 7.3),7.50(2H,t,J 7.1). 13 C NMR(151MHz,DMSO-d 6 )δ159.22,138.35,134.36,131.67,128.76,128.56,126.63,98.39. 11 B NMR (193 MHz, DMSO-d 6 )δ33.67.
3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3k).White solid(0.19g,82％yield)；mp 192-195℃,1H NMR(600MHz,DMSO-d6)δ10.48(1H,s),8.04(2H,dd,J 8.7,5.4),7.94(2H,d,J 6.7),7.56(1H,t,J 7.3),7.52(2H,t,J 7.4),7.44(2H,t,J 8.8).13C NMR(151MHz,DMSO-d6)δ164.79,163.15,158.96,134.35,131.62,129.24,129.19,128.74,123.76,123.74,116.65,116.50.11B NMR(193MHz,DMSO-d6)δ33.47.HRMS(ESI):m/z[M+H]+calculated for C13H11BN2OF:241.0943,found:249.0941.3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1,2,4,5-oxadiazaborole(3k).White solid(0.19g,82％yield);mp 192-195℃, 1 H NMR(600MHz,DMSO-d 6 )δ10.48(1H,s),8.04(2H,dd,J 8.7,5.4),7.94(2H,d,J 6.7),7.56(1H,t,J 7.3),7.52(2H,t,J 7.4),7.44(2H,t,J 8.8). 13 C NMR(151MHz,DMSO-d 6 )δ164.79,163.15,158.96,134.35,131.62,129.24,129.19,128.74,123.76,123.74,116.65,116.50. 11 B NMR (193 MHz, DMSO-d 6 )δ33.47. HRMS (ESI): m/z [M+H] + calculated for C 13 H 11 BN 2 OF: 241.0943, found: 249.0941.
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| US3137723A (en) * | 1961-09-25 | 1964-06-16 | Olin Mathieson | Boron containing heterocyclic compounds and process for producing them |
| US3692772A (en) * | 1968-09-03 | 1972-09-19 | Takeda Chemical Industries Ltd | Process for preparing 1,4-benzodiazepin-2-ones |
| US5387409A (en) * | 1990-01-18 | 1995-02-07 | Bracco International B.V. | Boronic acid adducts of rhenium dioxime and technetium-99m dioxime complexes containing a biochemically active group |
| CN114276375A (en) * | 2021-12-15 | 2022-04-05 | 重庆医科大学 | A kind of synthetic method of 1,3,2-benzodiazepine and derivatives thereof |
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| US3137723A (en) * | 1961-09-25 | 1964-06-16 | Olin Mathieson | Boron containing heterocyclic compounds and process for producing them |
| US3692772A (en) * | 1968-09-03 | 1972-09-19 | Takeda Chemical Industries Ltd | Process for preparing 1,4-benzodiazepin-2-ones |
| US5387409A (en) * | 1990-01-18 | 1995-02-07 | Bracco International B.V. | Boronic acid adducts of rhenium dioxime and technetium-99m dioxime complexes containing a biochemically active group |
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