CN104744303B - 2‑r‑4’‑溴甲基联苯及其制备方法 - Google Patents
2‑r‑4’‑溴甲基联苯及其制备方法 Download PDFInfo
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- CN104744303B CN104744303B CN201510082827.6A CN201510082827A CN104744303B CN 104744303 B CN104744303 B CN 104744303B CN 201510082827 A CN201510082827 A CN 201510082827A CN 104744303 B CN104744303 B CN 104744303B
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- water
- sulfuric acid
- concentrated sulfuric
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- 238000002360 preparation method Methods 0.000 title claims abstract description 46
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 81
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims abstract description 76
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims abstract description 63
- 239000003960 organic solvent Substances 0.000 claims abstract description 49
- 238000006243 chemical reaction Methods 0.000 claims abstract description 45
- 238000000034 method Methods 0.000 claims abstract description 41
- XUXNAKZDHHEHPC-UHFFFAOYSA-M sodium bromate Chemical compound [Na+].[O-]Br(=O)=O XUXNAKZDHHEHPC-UHFFFAOYSA-M 0.000 claims abstract description 38
- 235000010290 biphenyl Nutrition 0.000 claims abstract description 31
- 239000002904 solvent Substances 0.000 claims abstract description 29
- 239000002994 raw material Substances 0.000 claims abstract description 17
- 238000005893 bromination reaction Methods 0.000 claims abstract description 12
- 238000003756 stirring Methods 0.000 claims abstract description 11
- 230000031709 bromination Effects 0.000 claims abstract description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 81
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 42
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 36
- 239000004305 biphenyl Substances 0.000 claims description 29
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 29
- 239000000047 product Substances 0.000 claims description 23
- 239000012043 crude product Substances 0.000 claims description 21
- 238000001953 recrystallisation Methods 0.000 claims description 21
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
- 239000012071 phase Substances 0.000 claims description 15
- 238000007865 diluting Methods 0.000 claims description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 11
- 238000001816 cooling Methods 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 9
- 239000012074 organic phase Substances 0.000 claims description 9
- 238000010992 reflux Methods 0.000 claims description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 8
- 239000012046 mixed solvent Substances 0.000 claims description 7
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000003208 petroleum Substances 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 abstract description 21
- 230000008569 process Effects 0.000 abstract description 20
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 abstract description 17
- 229910052794 bromium Inorganic materials 0.000 abstract description 17
- 125000001246 bromo group Chemical group Br* 0.000 abstract description 7
- -1 methyl biphenyls Chemical class 0.000 abstract description 4
- 125000004429 atom Chemical group 0.000 abstract 1
- 230000009257 reactivity Effects 0.000 abstract 1
- ZGQVZLSNEBEHFN-UHFFFAOYSA-N 2-(4-methylphenyl)benzonitrile Chemical group C1=CC(C)=CC=C1C1=CC=CC=C1C#N ZGQVZLSNEBEHFN-UHFFFAOYSA-N 0.000 description 36
- 239000007787 solid Substances 0.000 description 29
- LFFIEVAMVPCZNA-UHFFFAOYSA-N 2-[4-(bromomethyl)phenyl]benzonitrile Chemical group C1=CC(CBr)=CC=C1C1=CC=CC=C1C#N LFFIEVAMVPCZNA-UHFFFAOYSA-N 0.000 description 13
- 238000005160 1H NMR spectroscopy Methods 0.000 description 12
- 238000001514 detection method Methods 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- IHNIAWHITVGYJJ-UHFFFAOYSA-N methyl 2-(4-methylphenyl)benzoate Chemical group COC(=O)C1=CC=CC=C1C1=CC=C(C)C=C1 IHNIAWHITVGYJJ-UHFFFAOYSA-N 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 238000012805 post-processing Methods 0.000 description 7
- 239000012295 chemical reaction liquid Substances 0.000 description 6
- 238000009776 industrial production Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- RMXGTMRDXKUUDJ-UHFFFAOYSA-N methyl 2-[4-(bromomethyl)phenyl]benzoate Chemical group COC(=O)C1=CC=CC=C1C1=CC=C(CBr)C=C1 RMXGTMRDXKUUDJ-UHFFFAOYSA-N 0.000 description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- MENYRYNFSIBDQN-UHFFFAOYSA-N 5,5-dibromoimidazolidine-2,4-dione Chemical compound BrC1(Br)NC(=O)NC1=O MENYRYNFSIBDQN-UHFFFAOYSA-N 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 229940127088 antihypertensive drug Drugs 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 238000013507 mapping Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 239000007800 oxidant agent Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003518 caustics Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Families Citing this family (8)
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CN108164434A (zh) * | 2017-12-27 | 2018-06-15 | 安徽太主科技发展有限公司 | 一种低成本4′-溴甲基-2-氰基联苯的制备方法 |
CN108129351A (zh) * | 2017-12-27 | 2018-06-08 | 安徽太主科技发展有限公司 | 一种4′-溴甲基-2-氰基联苯的制备方法 |
CN109507350A (zh) * | 2018-11-08 | 2019-03-22 | 南京明捷生物医药检测有限公司 | 一种测定坎地沙坦乙酯中2-氰基-4’-溴甲基联苯含量的方法 |
CN109796338B (zh) * | 2019-01-15 | 2022-05-06 | 深圳市第二人民医院 | 奥扎格雷中间体对溴甲基肉桂酸酯的合成方法 |
CN111974325A (zh) * | 2020-08-13 | 2020-11-24 | 浙江金立源药业有限公司 | 管道化合成对溴代甲基联苯甲酸甲酯的方法及其反应装置 |
CN112851549A (zh) * | 2021-03-11 | 2021-05-28 | 安徽云帆药业有限公司 | 一种溴化钠套用实验方法 |
CN112898182A (zh) * | 2021-03-11 | 2021-06-04 | 安徽云帆药业有限公司 | 一种制备4`-溴甲基-2-氰基联苯的合成方法 |
CN114276210A (zh) * | 2021-12-31 | 2022-04-05 | 上海合全药业股份有限公司 | 一种连续制备甲苯衍生物的一溴代物的方法 |
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TWI346108B (en) * | 2004-08-23 | 2011-08-01 | Bristol Myers Squibb Co | A method for preparing irbesartan and intermediates thereof |
HUP0900788A2 (en) * | 2009-12-16 | 2011-11-28 | Sanofi Aventis | Process for producing 4-bromomethyl-biphenyl derivatives |
CN103450021A (zh) * | 2013-09-11 | 2013-12-18 | 南开大学 | 一种改进的2-(2,-溴甲基苯基)-2-羰基乙酸甲酯的制备方法 |
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Effective date of registration: 20210112 Address after: 236000 intersection of Yingyang road and Chuangye Road, Taihe Economic Development Zone, Fuyang City, Anhui Province Patentee after: Fuyang xinyihua Pharmaceutical Technology Co.,Ltd. Patentee after: BEIJING SINEVA TECHNOLOGY Co.,Ltd. Patentee after: FUYANG SINEVA MATERIAL TECHNOLOGY Co.,Ltd. Address before: 100176 Beijing Daxing District economic and Technological Development Zone, Chuang Chuang nine Street 32 Building 1, two floors 201 rooms. Patentee before: BEIJING SINEVA TECHNOLOGY Co.,Ltd. |
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Effective date of registration: 20231013 Address after: 236000 intersection of Yingyang road and Chuangye Road, Taihe Economic Development Zone, Fuyang City, Anhui Province Patentee after: Fuyang xinyihua Pharmaceutical Technology Co.,Ltd. Address before: 236000 intersection of Yingyang road and Chuangye Road, Taihe Economic Development Zone, Fuyang City, Anhui Province Patentee before: Fuyang xinyihua Pharmaceutical Technology Co.,Ltd. Patentee before: BEIJING SINEVA TECHNOLOGY Co.,Ltd. Patentee before: FUYANG SINEVA MATERIAL TECHNOLOGY Co.,Ltd. |