CN113773340A - Method for efficiently synthesizing 9-halogenated o-carborane - Google Patents
Method for efficiently synthesizing 9-halogenated o-carborane Download PDFInfo
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- 238000000034 method Methods 0.000 title claims abstract description 28
- GJLPUBMCTFOXHD-UPHRSURJSA-N (11z)-1$l^{2},2$l^{2},3$l^{2},4$l^{2},5$l^{2},6$l^{2},7$l^{2},8$l^{2},9$l^{2},10$l^{2}-decaboracyclododec-11-ene Chemical class [B]1[B][B][B][B][B]\C=C/[B][B][B][B]1 GJLPUBMCTFOXHD-UPHRSURJSA-N 0.000 title claims abstract description 17
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 7
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims abstract description 19
- 230000002140 halogenating effect Effects 0.000 claims abstract description 11
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 40
- 230000015572 biosynthetic process Effects 0.000 claims description 17
- 238000003786 synthesis reaction Methods 0.000 claims description 17
- LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 claims description 16
- YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 claims description 8
- 239000003153 chemical reaction reagent Substances 0.000 claims description 8
- 229950009390 symclosene Drugs 0.000 claims description 8
- ZKWDCFPLNQTHSH-UHFFFAOYSA-N tribromoisocyanuric acid Chemical compound BrN1C(=O)N(Br)C(=O)N(Br)C1=O ZKWDCFPLNQTHSH-UHFFFAOYSA-N 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 7
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 239000003960 organic solvent Substances 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- MENYRYNFSIBDQN-UHFFFAOYSA-N 5,5-dibromoimidazolidine-2,4-dione Chemical compound BrC1(Br)NC(=O)NC1=O MENYRYNFSIBDQN-UHFFFAOYSA-N 0.000 claims description 3
- ZKLFRQSZDUSMQE-UHFFFAOYSA-N 5,5-dichloroimidazolidine-2,4-dione Chemical compound ClC1(Cl)NC(=O)NC1=O ZKLFRQSZDUSMQE-UHFFFAOYSA-N 0.000 claims description 3
- JKZOMQGCLXJWFO-UHFFFAOYSA-N 5,5-diiodoimidazolidine-2,4-dione Chemical compound IC1(I)NC(=O)NC1=O JKZOMQGCLXJWFO-UHFFFAOYSA-N 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 239000011261 inert gas Substances 0.000 claims description 3
- 229910052740 iodine Chemical group 0.000 claims description 3
- 239000011630 iodine Chemical group 0.000 claims description 3
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical group OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 abstract description 4
- 239000000758 substrate Substances 0.000 abstract description 4
- 238000006555 catalytic reaction Methods 0.000 abstract description 3
- 229910052751 metal Inorganic materials 0.000 abstract description 3
- 239000002184 metal Substances 0.000 abstract description 3
- 230000008901 benefit Effects 0.000 abstract description 2
- 238000011031 large-scale manufacturing process Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 54
- 239000000126 substance Substances 0.000 description 13
- 238000001035 drying Methods 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 238000004607 11B NMR spectroscopy Methods 0.000 description 9
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 8
- 229910052796 boron Inorganic materials 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 5
- 238000002360 preparation method Methods 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000012320 chlorinating reagent Substances 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000003912 environmental pollution Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012336 iodinating agent Substances 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000013064 chemical raw material Substances 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000006575 electron-withdrawing group Chemical group 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 150000002431 hydrogen Chemical group 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- 238000009206 nuclear medicine Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000002341 toxic gas Substances 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- -1 transition metal palladium acetate Chemical class 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
- C07F5/027—Organoboranes and organoborohydrides
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing 9-halogenated o-carborane without metal catalysis, belonging to the technical field of organic chemistry. The method comprises the following steps of reacting ortho-carborane serving as a raw material in the presence of a halogenating agent and hexafluoroisopropanol to obtain the 9-halogenated ortho-carborane in one step. The method does not need to add extra catalyst, can be smoothly carried out in the air at room temperature, has the advantages of simple operation, high yield, high product quality, wide substrate application range, easy large-scale production and the like, and can obtain a series of 9-halogenated derivatives of the o-carborane and the analogues thereof.
Description
Technical Field
The invention belongs to the technical field of elemental chemistry, and relates to a synthesis method of halogenated o-carborane, in particular to a method for synthesizing 9-halogenated o-carborane in a green manner without metal catalysis.
Background
Carborane and its derivatives have been used in many fields such as biomedicine, photochemistry, supramolecular and coordination chemistry, material chemistry, etc. due to their unique three-dimensional structure, low toxicity, and good thermal and chemical stability. In recent years, the development of carborane in the field of nuclear medicine is in a diversified trend, and the carborane not only has rich and varied applications in the field of traditional BNCT, but also plays an important role in the fields of radioactive molecular imaging, treatment and the like. The first boron neutron capture treatment experimental device in China in 8 months of 2020 is successfully developed in Dongguan of high-energy physics institute of Chinese academy of sciences, boron-containing drugs are urgently needed to be matched with the boron-containing experimental device, and the targeted radiotherapy treatment means is fully exerted to benefit cancer patients. Carborane derivatives are potential BNCT drugs as high boron content compounds.
The halocarborane is widely applied as an important chemical raw material and a medical intermediate, and the halogen atom can effectively change the physicochemical property and the physiological activity of the compound and can also be effectively converted into other functional groups through coupling reaction. Thus, selective halogenation of carboranes has received a great deal of attention from boronizers.
Traditionally, the synthesis of halogenated carborane is realized by taking halogen elementary substances (chlorine, bromine and iodine elementary substances) as halogen sources and lewis acid as a catalyst, and the reaction equation is as follows:
however, this method has a great disadvantage. Firstly, the selected halogenating reagent chlorine is a highly toxic gas and seriously pollutes the environment, and the bromine is also a corrosive toxic liquid; secondly, a catalyst needs to be added in the reaction process, the cost is high, and the reaction temperature is high. Therefore, the synthesis of halocarboranes, especially chlorocarboranes and bromocarboranes, by this method is very limited.
At present, in order to solve the problem of environmental pollution caused by synthesis of chlorocarborane, ferric trichloride is used as a chlorinating reagent, and the reaction equation is as follows:
although the synthesis of chlorocarborane is realized by the route, the product is a mixture of 8-chlorocarborane and 9-chlorocarborane; meanwhile, transition metal palladium acetate is used as a catalyst in the reaction process, so that the defects of poor reaction selectivity, high cost, high-temperature inert gas environment required for reaction, incapability of large-scale preparation and the like exist.
Therefore, it is very important to develop a synthetic method which meets the development direction of green chemistry and prepare the halogenated o-carborane with high selectivity by adopting a low-toxicity or non-toxic halogenating reagent.
Disclosure of Invention
In view of the above, the invention provides a simple method for synthesizing 9-halogenated o-carborane in one step by adding a halogenating reagent at room temperature under the condition of no metal catalysis. The method avoids the defects of harsh reaction conditions, high catalytic cost, high reaction temperature, serious environmental pollution and the like in the traditional preparation method, and the 9-halogenated o-carborane can be obtained with high selectivity by adopting the method.
The invention discloses a method for synthesizing 9-halogenated carborane, which comprises the following steps: the method comprises the following steps of taking o-carborane 1 as a raw material, and reacting in the presence of a halogenating agent and an organic solvent to obtain 9-halogenated o-carborane 2, 3 and 4. The reaction equation of the synthetic route is as follows:
wherein R is selected from hydrogen, C1-C8 alkyl, halogenated C1-C4 alkyl, C1-C4 alkylthio, phenyl and substituted phenyl, and the substituent in the substituted phenyl is C1-C4 alkyl, halogen, C1-C4 alkanoyl, C1-C4 alkoxycarbonyl and trifluoromethyl; or two R groups form a 4-8 membered ring; x is selected from chlorine, bromine and iodine.
Further, in the above technical solution, the organic solvent is trifluoroethanol or hexafluoroisopropanol.
Further, in the above technical solution, the halogenating agent is selected from chlorinating agent, brominating agent or iodinating agent, including trichloroisocyanuric acid, N-chlorosuccinimide, dichlorohydantoin, tribromoisocyanuric acid, N-bromosuccinimide, dibromohydantoin, N-iodosuccinimide, diiodohydantoin.
Wherein the iodinating agent comprises N-iodosuccinimide and diiodohydantoin; the chlorinating agent comprises trichloroisocyanuric acid, N-chlorosuccinimide and dichlorohydantoin; the brominating agent comprises tribromoisocyanuric acid, N-bromosuccinimide and dibromohydantoin.
Further, in the above technical scheme, the molar ratio of the compound 1 to the halogenating agent is 1: 0.5-3.
Further, in the above technical scheme, the reaction temperature is 0-80 ℃.
Furthermore, in the technical scheme, the reaction is carried out in the air without the protection of inert gas.
Advantageous effects of the invention
1. The method is simple to operate, only the substrate o-carborane and the halogenated reagent are needed to be added into the solvent, other reagents or complex reaction flows are not needed to be added in the synthesis process, and the technological operation process is simple;
2. in the reaction process, the needed halogenated reagent is cheap and easy to obtain, and most of the halogenated reagent can be directly purchased; the three wastes generated in the reaction process are less, the environmental pollution is less, and the method has the potential of large-scale synthesis.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments. The embodiment is implemented on the premise of the technical scheme of the invention, and a detailed implementation mode and a specific operation process are given, but the protection scope of the invention is not limited to the following embodiment.
Example 1
Taking the synthesis of 9-chloro-1, 2-dimethyl-o-carborane (2a), 9-bromo-1, 2-dimethyl-o-carborane (3a) and 9-iodo-1, 2-dimethyl-o-carborane (4a) by using 1, 2-dimethyl-o-carborane (1a) as an example, the reaction conditions are optimized as follows:
after condition screening, the optimal condition for screening synthesis 2 is labeled 12: reacting 1.0 time of trichloroisocyanuric acid in a hexafluoroisopropanol solvent at room temperature for 36 hours; the optimal conditions for synthesis 3 are numbered 16: reacting 1.0 time of tribromoisocyanuric acid in hexafluoroisopropanol solvent at room temperature for 36 hours; the optimal conditions for synthesis 4 are numbered 21: 2.0 times of N-iodosuccinimide is adopted to react in a hexafluoroisopropanol solvent for 24 hours at room temperature. The typical procedure is as follows:
a: preparation of 9-chloro-o-carborane 2a
1, 2-dimethyl-o-carborane 1a (344mg,2mmol), trichloroisocyanuric acid (232mg) and 15mL hexafluoroisopropanol were added into a reaction flask, and the mixture was stirred at room temperature for reaction for 36 hours. Adding 15mL of water into the system, extracting with 30mL of n-hexane for three times, combining organic phases, drying by anhydrous sodium sulfate, and carrying out rotary drying to obtain a product 2a with the yield of 94%.1H NMR(600MHz,CDCl3)δ:2.05(s,3H),2.02(s,3H)；13C NMR(151MHz,CDCl3)δ:71.28,63.46,23.37,21.46；11B NMR(151MHz,CDCl3)δ:6.07,-4.69,-9.67,-10.87；HRMS:m/z calc.for C2 10B1 11 B9H15Cl[M-H]-206.1759; found,206.1766 nuclear magnetic data analysis: chemical shift δ 2.05, single peak, assigned to three hydrogens of the methyl group; chemical shift δ 2.02, singlet, assigned to another methyl triplet hydrogen; chemical shift δ 71.28, single peak, assigned to one carbon on the carborane cage; chemical shift δ 63.46, single peak, assigned to another carbon on the carborane cage; chemical shift δ 23.37, singlet, assigned to carbon on methyl; chemical shift δ 21.46, single peak, assigned to another carbon on methyl; chemical shift delta 6.07, ascribed to boron number 9; chemical shift delta-4.69, assigned as boron number 12; chemical shift delta-9.67, boron assigned to positions 3, 4, 5, 6, 7, 11; chemical shift delta-10.87, and attribution as boron No. 8 and 10. And (3) combining the nuclear magnetism and mass spectrum test results to determine that the product is 9-chlorine-1, 2-dimethyl o-carborane.
B: preparation of 9-bromo-o-carborane 3a
1, 2-dimethyl-o-carborane 1a (344mg,2mmol), tribromoisocyanuric acid (363mg) and 15mL hexafluoroisopropanol were added into a reaction flask, and the reaction was stirred at room temperature for 36 h. Adding 15mL of water into the system, extracting with 30mL of n-hexane for three times, combining organic phases, drying by anhydrous sodium sulfate, and carrying out spin drying to obtain a product 3a with the yield of 96%.1H NMR(600MHz,CDCl3)δ:2.06(s,3H),1.98(s,3H)；13C NMR(100MHz,CDCl3)δ:72.49,65.85,23.07,22.02；11B NMR(151MHz,CDCl3)δ:-1.30,-4.34,-8.97,-9.42,-10.21；HRMS:m/z calc.for C2 10B1 11B9H15Br[M-H]-,250.1256；found,250.1272.
C: preparation of 9-iodo-o-carborane 4a
1, 2-dimethyl-o-carborane 1a (344mg,02mmol), N-iodosuccinimide (450mg) and 15mL hexafluoroisopropanol were added to a reaction flask, and the reaction was stirred at room temperature for 24 hours. 15mL of water and 30mL of n-hexane are added into the system for extraction three times, organic phases are combined, dried by anhydrous sodium sulfate and dried by spinning to obtain a product 4a with the yield of 97%.1H NMR(600MHz,CDCl3)δ:2.06(s,3H),1.91(s,3H)；13C NMR(151MHz,CDCl3)δ:74.27,69.88,23.12,23.01；11B NMR(151MHz,CDCl3)δ:-3.60,-8.07,-8.67,-9.20,-17.98；HRMS:m/z calc.for C4 10B2 11B8H15I[M-H]-,297.1140；found,297.1144.
Example 2
In a reaction flask, o-carborane 1b (288mg,2mmol), trichloroisocyanuric acid (232mg) and 15mL hexafluoroisopropanol were added, and the reaction was stirred at room temperature for 36 h. Adding 15mL of water into the system, extracting with 30mL of normal hexane for three times, combining organic phases, drying by anhydrous sodium sulfate, and carrying out rotary drying to obtain a product 2b with the yield of 94%.1H NMR(600MHz,CDCl3)δ:3.56(s,1H),3.44(s,1H)；13C NMR(151MHz,CDCl3)δ:52.04,44.29；11B NMR(151MHz,CDCl3)δ:7.52,-2.02,-8.75,-13.83,-15.13,-16.29；HRMS:m/z calc.for C2 10B11B9 H11Cl[M-H]-,178.1442；found,178.1448.
Example 3
In a reaction flask, o-carborane 1b (288mg, 2) was addedmmol), tribromoisocyanuric acid (363mg) and 15mL hexafluoroisopropanol were stirred at room temperature for 36 h. Adding 15mL of water into the system, extracting with 30mL of n-hexane for three times, combining organic phases, drying by anhydrous sodium sulfate, and carrying out spin drying to obtain a product 3b with the yield of 97%.1H NMR(400MHz,CDCl3)δ:3.62(s,2H)；13C NMR(100MHz,CDCl3)δ:53.22,46.73；11B NMR(128MHz,CDCl3)δ:0.01,-1.73,-8.39,-13.56,-14.49,-15.69；HRMS:m/z calc.for C2 10B1 11B9H11Br[M-H]-,222.0950；found,222.0950.
Example 4
In a reaction flask, o-carborane 1b (288mg,2mmol), N-iodosuccinimide (450mg) and 15mL hexafluoroisopropanol were added, and the reaction was stirred at room temperature for 24 h. Adding 15mL of water into the system, extracting with 30mL of normal hexane for three times, combining organic phases, drying by anhydrous sodium sulfate, and carrying out rotary drying to obtain a product 4b with the yield of 96%.1H NMR(600MHz,CDCl3)δ:3.88(s,1H),3.68(s,1H)；13C NMR(100MHz,CDCl3)δ:54.98,50.84；11B NMR(151MHz,CDCl3)δ:-0.90,-7.48,-12.82,-13.45,-14.73,-16.62；HRMS:m/z calc.for C2 10B2 11B8H11I[M-H]-,269.0826；found,269.0838.
Example 5
1, 2-diphenyl-o-carborane 1c (592mg,2mmol), trichloroisocyanuric acid (232mg) and 15mL hexafluoroisopropanol are added into a reaction flask, and the mixture is stirred and reacted for 36 hours at the temperature of 60 ℃. Hexafluoroisopropanol was removed by distillation under reduced pressure, and column chromatography gave product 2c in 82% yield.1H NMR(600MHz,CDCl3)δ:7.40(s,4H),7.25(d,J＝4.8Hz,2H),7.14(d,J＝7.1Hz,4H)；13C NMR(151MHz,CDCl3)δ:130.82,130.51,130.44,129.81,128.96,128.41,128.39,83.11,75.23；11B NMR(151MHz,CDCl3)δ:8.51,2.25,-9.94,-10.70,-12.82；HRMS:m/z calc.for C14 10B1 11B9H19Cl[M]-,331.2152；found,331.2145.
Example 6
1, 2-diphenyl-o-carborane 1c (592mg,2mmol), tribromoisocyanuric acid (363mg) and 15mL hexafluoroisopropanol are added into a reaction flask, the mixture is stirred and reacted for 36 hours at the temperature of 60 ℃, the hexafluoroisopropanol is removed after reduced pressure distillation, and the product 3c is obtained through chromatographic separation of a column layer, wherein the yield is 72%.1H NMR(600MHz,CDCl3)δ:7.39(s,4H),7.25(s,2H),7.15(d,J＝6.6Hz,4H)；13C NMR(151MHz,CDCl3)δ:130.67,130.55,130.47,1129.72,129.31,128.43,128,41,84.21,77.71；11B NMR(151MHz,CDCl3)δ:1.25,-1.80,-9.52,-12.15；HRMS:m/z calc.for C14 10B1 11B9H19Br[M]-,375.1648；found,375.1640.
Example 7
1, 2-Diphenylo-carborane 1c (592mg,2mmol), N-iodosuccinimide (450mg) and 15mL hexafluoroisopropanol were added to a reaction flask, and the reaction was stirred at 60 ℃ for 24 hours. Hexafluoroisopropanol was removed by distillation under reduced pressure and the product 4c was obtained by column chromatography in 92% yield.1H NMR(600MHz,CDCl3)δ:7.40-7.38(m,4H),7.26(s,2H),7.15(s,4H)；13C NMR(151MHz,CDCl3)δ:130.57,130.50,130.47,130.45,130.02,129.61,128.44,128.42,85.85,81.93；11B NMR(151MHz,CDCl3)δ:-1.02,-8.77,-11.24,-15.33；HRMS:m/z calc.for C14 10B2 11B8H19I[M-H]-,421.1458；found,421.1466.
Example 8
To further verify the reaction mechanism, the reaction was carried out using a trisubstituted methyl substrate 1w under the same conditions and it was found that the reaction could still proceed. The reaction was not continued under the same conditions at room temperature to reflux using the product 2a/3a/4 a. This is because the halogen is an electron withdrawing group, which reduces the reactivity of the carborane.
Example 9
Following the typical procedure described above in examples 2-7, the results after replacement of the other reaction substrates were as follows:
athe reaction temperature was 60 ℃ and the rest is not indicated at room temperature.
The above is only a preferred embodiment of the present invention, and it should be noted that the above preferred embodiment should not be considered as limiting the present invention, and the protection scope of the present invention should be subject to the scope defined by the claims. It will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the spirit and scope of the invention, and these modifications and adaptations should be considered within the scope of the invention.
Claims (8)
1. A method for synthesizing 9-halogenated o-carborane is characterized by comprising the following steps: reacting ortho-carborane 1 serving as a raw material in the presence of a halogenating reagent and an organic solvent to obtain 9-halogenated ortho-carborane 2, 3 and 4; the reaction equation is expressed as follows:
wherein R is selected from hydrogen, C1-C8 alkyl, halogenated C1-C4 alkyl, C1-C4 alkylthio, phenyl and substituted phenyl, and the substituent in the substituted phenyl is C1-C4 alkyl, halogen, C1-C4 alkanoyl, C1-C4 alkoxycarbonyl and trifluoromethyl; or two R groups form a 4-8 membered ring; x is selected from chlorine, bromine and iodine.
2. The method of synthesis according to claim 1, characterized in that: the organic solvent is selected from trifluoroethanol or hexafluoroisopropanol.
3. The method of synthesis according to claim 2, characterized in that: the organic solvent is selected from hexafluoroisopropanol.
4. The method of synthesis according to claim 1, characterized in that: the halogenating agent comprises trichloroisocyanuric acid, N-chlorosuccinimide, dichlorohydantoin, tribromoisocyanuric acid, N-bromosuccinimide, dibromohydantoin, N-iodosuccinimide and diiodohydantoin.
5. The method of synthesis according to claim 4, characterized in that: the halogenating agent is trichloroisocyanuric acid, tribromoisocyanuric acid or N-iodosuccinimide.
6. The method of synthesis according to claim 1, characterized in that: the mol ratio of the o-carborane to the halogenating agent is 1: 0.5-3.
7. The method of synthesis according to claim 1, characterized in that: the reaction temperature is 0-80 ℃.
8. The method of synthesis according to any one of claims 1 to 7, characterized in that: the reaction is carried out in air without inert gas protection.
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| CN114709557A (en) * | 2022-04-13 | 2022-07-05 | 南京工业大学 | Design synthesis of covalent organic framework material of post-modified carborane and application of covalent organic framework material in lithium-sulfur battery diaphragm |
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| CN114591357A (en) * | 2022-03-07 | 2022-06-07 | 郑州大学 | Synthesis method of B (9) -amido-o-carborane compound |
| CN114709557A (en) * | 2022-04-13 | 2022-07-05 | 南京工业大学 | Design synthesis of covalent organic framework material of post-modified carborane and application of covalent organic framework material in lithium-sulfur battery diaphragm |
| CN114709557B (en) * | 2022-04-13 | 2023-10-27 | 南京工业大学 | Design synthesis of covalent organic framework material of post-modified carborane and application of covalent organic framework material in lithium-sulfur battery diaphragm |
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