CN1295207C - Method for preparing 4-dibromo-6-nitro methylbenzene - Google Patents
Method for preparing 4-dibromo-6-nitro methylbenzene Download PDFInfo
- Publication number
- CN1295207C CN1295207C CNB2003101090327A CN200310109032A CN1295207C CN 1295207 C CN1295207 C CN 1295207C CN B2003101090327 A CNB2003101090327 A CN B2003101090327A CN 200310109032 A CN200310109032 A CN 200310109032A CN 1295207 C CN1295207 C CN 1295207C
- Authority
- CN
- China
- Prior art keywords
- bromo
- methyl
- dibromo
- present
- hydrobromic acid
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 15
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims abstract description 16
- MZYLMACPWDPBQN-UHFFFAOYSA-N 2-bromo-4-methyl-5-nitroaniline Chemical compound CC1=CC(Br)=C(N)C=C1[N+]([O-])=O MZYLMACPWDPBQN-UHFFFAOYSA-N 0.000 claims abstract description 13
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000000047 product Substances 0.000 claims abstract description 12
- 239000007864 aqueous solution Substances 0.000 claims abstract description 9
- 239000007810 chemical reaction solvent Substances 0.000 claims abstract description 9
- 239000012043 crude product Substances 0.000 claims abstract description 9
- 235000010288 sodium nitrite Nutrition 0.000 claims abstract description 8
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims abstract description 7
- 230000031709 bromination Effects 0.000 claims abstract description 6
- 238000005893 bromination reaction Methods 0.000 claims abstract description 6
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 claims abstract description 6
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 5
- 239000000243 solution Substances 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 3
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 2
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 2
- 230000002140 halogenating effect Effects 0.000 claims 4
- HXBMIQJOSHZCFX-UHFFFAOYSA-N 1-(bromomethyl)-2-nitrobenzene Chemical class [O-][N+](=O)C1=CC=CC=C1CBr HXBMIQJOSHZCFX-UHFFFAOYSA-N 0.000 claims 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 2
- VKEQBMCRQDSRET-UHFFFAOYSA-N Methylone Chemical compound CNC(C)C(=O)C1=CC=C2OCOC2=C1 VKEQBMCRQDSRET-UHFFFAOYSA-N 0.000 claims 1
- 229960001701 chloroform Drugs 0.000 claims 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims 1
- OJFOMLFOBYEZNH-UHFFFAOYSA-N 1,2-dibromo-4-methyl-5-nitrobenzene Chemical compound CC1=CC(Br)=C(Br)C=C1[N+]([O-])=O OJFOMLFOBYEZNH-UHFFFAOYSA-N 0.000 abstract description 12
- 238000006193 diazotization reaction Methods 0.000 abstract description 9
- 239000002994 raw material Substances 0.000 abstract description 7
- 238000005658 halogenation reaction Methods 0.000 abstract description 4
- 238000004128 high performance liquid chromatography Methods 0.000 abstract description 4
- 238000002844 melting Methods 0.000 abstract description 4
- 230000008018 melting Effects 0.000 abstract description 4
- 239000002535 acidifier Substances 0.000 abstract description 2
- 239000003054 catalyst Substances 0.000 abstract description 2
- 238000000354 decomposition reaction Methods 0.000 abstract description 2
- 238000009776 industrial production Methods 0.000 abstract description 2
- 238000005121 nitriding Methods 0.000 abstract 1
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000006396 nitration reaction Methods 0.000 description 2
- RZXMPPFPUUCRFN-UHFFFAOYSA-N p-toluidine Chemical compound CC1=CC=C(N)C=C1 RZXMPPFPUUCRFN-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 1
- LDCPXNOCWDGYIU-UHFFFAOYSA-N 1,2-dibromo-4-methylbenzene Chemical compound CC1=CC=C(Br)C(Br)=C1 LDCPXNOCWDGYIU-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
- AFBPFSWMIHJQDM-UHFFFAOYSA-N N-methyl-N-phenylamine Natural products CNC1=CC=CC=C1 AFBPFSWMIHJQDM-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种3，4-二溴-6-硝基甲苯的制备方法。本发明以2-溴-4-甲基-5-硝基苯胺为原料，氢溴酸水溶液为酸化剂、溴化亚铜为催化剂溶于卤代反应溶剂中，与亚硝酸钠进行反应，重氮化的同时直接溴化，分离出粗产物，然后进行纯化，即获得本发明的目标产物。用本发明制备方法得到的3，4-二溴-6-硝基甲苯，纯度达到98%(HPLC)以上，熔点为82.8—84.2℃，总得率71%以上。本发明与现有技术相比较，操作简便，操作过程可控性强，重氮化与溴代同时完成，减少了分解，产品质量稳定，适于工业化生产。The invention discloses a preparation method of 3,4-dibromo-6-nitrotoluene. The present invention uses 2-bromo-4-methyl-5-nitroaniline as a raw material, hydrobromic acid aqueous solution as an acidifying agent, and cuprous bromide as a catalyst dissolved in a halogenation reaction solvent, and reacts with sodium nitrite. Direct bromination at the same time of nitriding, the crude product is separated, and then purified to obtain the target product of the present invention. The 3,4-dibromo-6-nitrotoluene obtained by the preparation method of the present invention has a purity of over 98% (HPLC), a melting point of 82.8-84.2°C, and a total yield of over 71%. Compared with the prior art, the invention has the advantages of simple operation, strong controllability of the operation process, simultaneous completion of diazotization and bromination, reduced decomposition, stable product quality, and is suitable for industrial production.
Description
技术领域technical field
本发明涉及一种3，4-二溴-6-硝基甲苯的制备方法。The invention relates to a preparation method of 3,4-dibromo-6-nitrotoluene.
背景技术Background technique
3，4-二溴-6-硝基甲苯是一种有机合成中间体，可以作为合成吲哚类药物的中间体，其结构式如下：3,4-dibromo-6-nitrotoluene is an intermediate in organic synthesis, which can be used as an intermediate in the synthesis of indole drugs. Its structural formula is as follows:
现有技术中，J.Chem.Soc.105.(1914)515上报道了用2-溴-4-甲基-5-硝基苯胺为原料，经重氮化反应，将过滤得到的重氮化溶液，滴入氢溴酸-溴化亚铜溶液中，加热分解，溴代，得到3，4二溴-6-硝基甲苯。其中2-溴-4-甲基-5-硝基苯胺的重氮化困难，得率低，重氮盐在水中的溶解度低，工业化前景不理想。In the prior art, J.Chem.Soc.105.(1914) 515 reported using 2-bromo-4-methyl-5-nitroaniline as a raw material, through diazotization reaction, the diazo obtained by filtration solution, drop into hydrobromic acid-cuprous bromide solution, decompose by heating, and brominate to obtain 3,4 dibromo-6-nitrotoluene. Wherein the diazotization of 2-bromo-4-methyl-5-nitroaniline is difficult, the yield is low, the solubility of diazonium salt in water is low, and the industrialization prospect is not ideal.
Chem.Ber.14；1881，417-420上报道了以3，4-二溴甲苯为原料，经硝化得到3，4-二溴-6-硝基甲苯；10-Organic Chemistry，1944；5205-5206上报道了以1，2-二溴-4-异丙基-5-甲苯为原料，在苯酚和发烟硝酸的作用下生成3，4-二溴-6-硝基甲苯，但二种方法原料反应困难，所得产物中付产物较多，工业化前景不理想。Chem.Ber.14; 1881,417-420 reported that 3,4-dibromotoluene was used as raw material to obtain 3,4-dibromo-6-nitrotoluene through nitration; 10-Organic Chemistry, 1944; 5205- 5206 reported that 1,2-dibromo-4-isopropyl-5-toluene was used as raw material to generate 3,4-dibromo-6-nitrotoluene under the action of phenol and fuming nitric acid, but the two The reaction of raw materials in the method is difficult, and there are many by-products in the obtained product, and the industrialization prospect is not ideal.
发明内容Contents of the invention
本发明解决的技术问题是提供一种3，4-二溴-6-硝基甲苯的制备方法，以克服现有技术中重氮化困难，反应得率低，所得产物中付产物较多的缺点。The technical problem solved by the present invention is to provide a kind of preparation method of 3,4-dibromo-6-nitrotoluene, to overcome the diazotization difficulty in the prior art, the reaction yield is low, and there are many by-products in the obtained product shortcoming.
本发明的技术构思是这样的：以2-溴-4-甲基-5-硝基苯胺为原料，氢溴酸水溶液为酸化剂、溴化亚铜为催化剂溶于卤代反应溶剂中，与亚硝酸钠进行反应，重氮化的同时直接溴化，分离出粗产物，然后进行纯化，即获得本发明的目标产物。The technical design of the present invention is such: take 2-bromo-4-methyl-5-nitroaniline as raw material, hydrobromic acid aqueous solution is acidifying agent, cuprous bromide is dissolved in the halogenation reaction solvent as catalyst, and Sodium nitrite is reacted, diazotized and simultaneously brominated directly, the crude product is separated, and then purified to obtain the target product of the present invention.
本发明的技术方案：将2-溴-4-甲基-5-硝基苯胺，氢溴酸水溶液、溴化亚铜分别加入卤代反应溶剂中，与亚硝酸钠溶液在-5～10℃条件下反应，重氮化的同时直接溴化，从反应产物中收集目的产物3，4-二溴-6-硝基甲苯，用有机溶剂进行纯化。Technical scheme of the present invention: add 2-bromo-4-methyl-5-nitroaniline, hydrobromic acid aqueous solution, and cuprous bromide into the halogenation reaction solvent respectively, and mix with sodium nitrite solution at -5～10°C Reaction under conditions, diazotization and direct bromination at the same time, collect the target product 3,4-dibromo-6-nitrotoluene from the reaction product, and purify with an organic solvent.
按照本发明，所说的氢溴酸水溶液中，含氢溴酸的浓度为重量百分比40％-50％，特别是48％的氢溴酸。According to the present invention, in the said aqueous solution of hydrobromic acid, the concentration of hydrobromic acid is 40%-50% by weight, especially 48% hydrobromic acid.
所说的卤代反应溶剂是二氯甲烷，三氯甲烷，四氯化碳，1，2-二氯乙烷，1，1，1-三氯乙烷中的一种或一种以上。优选四氯化碳.The halogenated reaction solvent is one or more of dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and 1,1,1-trichloroethane. Carbon tetrachloride is preferred.
按照本发明，配料比为2-溴-4-甲基-5-硝基苯胺∶氢溴酸∶溴化亚铜∶亚硝酸钠＝1.0∶0.8-1.1∶0.2-1.0∶0.9-1.1，摩尔比，2-溴-4-甲基-5-硝基苯胺与卤代反应溶剂的重量体积比为1.0∶4.0-5.5。According to the present invention, the proportioning ratio is 2-bromo-4-methyl-5-nitroaniline: hydrobromic acid: cuprous bromide: sodium nitrite=1.0: 0.8-1.1: 0.2-1.0: 0.9-1.1, mole Ratio, the weight volume ratio of 2-bromo-4-methyl-5-nitroaniline to the halogenation reaction solvent is 1.0:4.0-5.5.
从反应产物中收集目的产物3，4-二溴-6-硝基甲苯可包括如下步骤：反应完成后加水，分出有机层，蒸除溶剂，得到的粗产物纯化，得到本发明的目标产物，Collecting the target product 3 from the reaction product, 4-dibromo-6-nitrotoluene may include the following steps: add water after the reaction is completed, separate the organic layer, evaporate the solvent, and purify the obtained crude product to obtain the target product of the present invention ,
按照本发明，纯化的有机溶剂采用甲醇、乙醇、乙酸甲酯，乙酸乙酯中的一种或一种以上，优选采用乙醇，粗产物与纯化溶剂的重量体积比为1.0∶2.0-3.5。According to the present invention, the purified organic solvent is one or more of methanol, ethanol, methyl acetate, and ethyl acetate, preferably ethanol, and the weight-to-volume ratio of the crude product to the purification solvent is 1.0: 2.0-3.5.
本发明的反应式如下：Reaction formula of the present invention is as follows:
用本发明制备方法得到的3，4-二溴-6-硝基甲苯，纯度达到98％(HPLC)以上，熔点为82.8-84.2℃，总得率71％以上。The 3,4-dibromo-6-nitrotoluene obtained by the preparation method of the present invention has a purity of over 98% (HPLC), a melting point of 82.8-84.2°C, and a total yield of over 71%.
本发明所使用的原料2-溴-4-甲基-5-硝基苯胺根据JACS.VOL72，2972报道的方法以对甲苯胺为起始原料，经过乙酰化，溴代水解硝化制备得到。The raw material 2-bromo-4-methyl-5-nitroaniline used in the present invention is prepared according to the method reported in JACS.VOL72, 2972 by using p-toluidine as the starting material through acetylation, bromohydrolysis and nitration.
本发明与现有技术相比较，重氮化反应的同时进行溴代，操作简便，操作过程可控性强，重氮化与溴代同时完成，减少了分解，产品质量稳定，适于工业化生产。Compared with the prior art, the present invention carries out bromination at the same time as the diazotization reaction, and is easy to operate, and the operation process is highly controllable. The diazotization and bromination are completed at the same time, reducing decomposition, stable product quality, and suitable for industrial production. .
具体实施方式Detailed ways
下面通过实施例对本发明作进一步说明本发明，但实施例并不限制本发明的保护范围。The present invention will be further described below by embodiment, but embodiment does not limit protection scope of the present invention.
实施例1Example 1
在带有搅拌、温度计、滴液装置的500ml三口烧瓶中分别加入2-溴-4-甲基-5-硝基苯胺23.2g，48％氢溴酸(重量百分比)180ml，水100ml，溴化亚铜7g，四氯化碳100ml，溶解冷却，搅拌下滴加15％的亚硝酸钠(重量百分比)水溶液，重氮化用碘化钾试纸测定终点，反应完全后加水，分出有机层，蒸除溶剂，得到3，4-二溴-6-硝基甲苯粗品27.3g，得率92.5％；在粗品中加入乙醇60ml溶解进行结晶纯化，得到21g产品，纯度为98.53％(HPLC)，熔点为82.8-84.2℃，得率为76.9％，总得率为71.2％。Add 23.2 g of 2-bromo-4-methyl-5-nitroaniline, 180 ml of 48% hydrobromic acid (percentage by weight), and 100 ml of water into a 500 ml three-neck flask equipped with stirring, thermometer, and dripping device, and bromide Cuprous 7g, carbon tetrachloride 100ml, dissolve and cool, add dropwise 15% sodium nitrite (weight percent) aqueous solution under stirring, diazotization uses potassium iodide test paper to measure the end point, add water after the reaction is complete, separate the organic layer, evaporate solvent to obtain 27.3g of 3,4-dibromo-6-nitrotoluene crude product, yield 92.5%; add ethanol 60ml to dissolve in crude product and carry out crystallization purification, obtain 21g product, purity is 98.53% (HPLC), melting point is 82.8 -84.2°C, the yield was 76.9%, and the total yield was 71.2%.
实施例2Example 2
在带有搅拌、温度计、滴液装置的500ml的三口烧瓶中分别加入2-溴-4-甲基-5-硝基苯胺23.2g，48％氢溴酸(重量百分比)150ml，水150ml，溴化亚铜4g，四氯化碳120ml，溶解冷却，搅拌下滴加15％的亚硝酸钠(重量百分比)水溶液，重氮化用KI试纸测定终点，反应完全后加入水，分出有机层，蒸除溶剂，得到3，4-二溴-6-硝基甲苯粗品26.1g，得率88.4％；在粗品中加入乙醇90ml溶解进行结晶纯化，得到19.2g产品，纯度为98.48％(HPLC)，熔点为82.5-84.5℃，得率73.5％，总得率为65.0％。Add 23.2 g of 2-bromo-4-methyl-5-nitroaniline, 150 ml of 48% hydrobromic acid (percentage by weight), 150 ml of water, and Cuprous chloride 4g, carbon tetrachloride 120ml, dissolve and cool, add dropwise 15% sodium nitrite (weight percent) aqueous solution under stirring, measure the end point with KI test paper for diazotization, add water after the reaction is complete, separate the organic layer, The solvent was evaporated to obtain 26.1 g of 3,4-dibromo-6-nitrotoluene crude product, with a yield of 88.4%; 90 ml of ethanol was added to the crude product for crystallization and purification to obtain 19.2 g of product with a purity of 98.48% (HPLC). The melting point is 82.5-84.5°C, the yield is 73.5%, and the total yield is 65.0%.
Claims (10)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2003101090327A CN1295207C (en) | 2003-12-03 | 2003-12-03 | Method for preparing 4-dibromo-6-nitro methylbenzene |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2003101090327A CN1295207C (en) | 2003-12-03 | 2003-12-03 | Method for preparing 4-dibromo-6-nitro methylbenzene |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1623974A CN1623974A (en) | 2005-06-08 |
| CN1295207C true CN1295207C (en) | 2007-01-17 |
Family
ID=34758817
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2003101090327A Expired - Fee Related CN1295207C (en) | 2003-12-03 | 2003-12-03 | Method for preparing 4-dibromo-6-nitro methylbenzene |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1295207C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102952039A (en) * | 2012-11-15 | 2013-03-06 | 大连九信生物化工科技有限公司 | Synthesis method of 4-chloro-2-trifluoromethylbenzonitrile |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1286244A (en) * | 1999-08-27 | 2001-03-07 | 拜尔公司 | Method for preparing 2-chloro-4-nitroalkylbenzene |
-
2003
- 2003-12-03 CN CNB2003101090327A patent/CN1295207C/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1286244A (en) * | 1999-08-27 | 2001-03-07 | 拜尔公司 | Method for preparing 2-chloro-4-nitroalkylbenzene |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1623974A (en) | 2005-06-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| WO2009040367A1 (en) | Process for the preparation of fluorine containing organic compound | |
| KR102615440B1 (en) | Process for producing 3,7-bis-(dimethylamino)-phenothiazine-5-ium chloride or bromide | |
| WO2023104063A1 (en) | Preparation method for ioversol hydrolysate | |
| CN1295207C (en) | Method for preparing 4-dibromo-6-nitro methylbenzene | |
| CN106146330B (en) | A kind of method for preparing eltrombopag olamine intermediate | |
| CN113461615B (en) | Preparation method of 4-fluoro-1H-pyrazole | |
| CN114524718A (en) | Method for preparing high-purity o-phthalaldehyde from diester phthalate | |
| JP2021195344A (en) | Method for producing 5-bromo-2-halogenated benzoic acid | |
| CN105189447B (en) | The method for manufacturing nitrobenzene compound | |
| CN101088985A (en) | Amfebutamone hydrochloride synthesizing process | |
| CN102675148B (en) | The preparation method of p-hydroxybenzonitrile | |
| CN103073467A (en) | Preparation method of alpha-carbonyl sulfur ylide derivative | |
| JP4161290B2 (en) | Process for producing pyrimidinyl alcohol derivatives and synthetic intermediates thereof | |
| CN103664901B (en) | A kind of rizatriptan benzoate preparation method | |
| CN101219955B (en) | Method for synthesizing o-nitrobenzaldehyde compounds | |
| CN111517904A (en) | Preparation method of sulfonyl acetonitrile compound | |
| CN103450046B (en) | Method for preparing para hydroxybenzene acetonitrile | |
| CN106317060B (en) | A kind of preparation method of hydrochloric acid conivaptan | |
| CN100999483A (en) | Preparation process of p-nitro phenyl hydrazine hydrochloride | |
| JP2021195320A (en) | Method for producing 5-bromo-2-halogenated benzoic acid | |
| CN116444382B (en) | Synthesis method of 4-iodo-2-methylaniline | |
| CN111072554A (en) | Synthesis method of 4-bromo-2-chloro-6-methoxypyridine | |
| CN113233957B (en) | Preparation method of 2-bromo-5-iodo-benzyl alcohol | |
| CN117720432B (en) | A method for preparing arylhydrazine compounds | |
| CN102731600B (en) | Preparation method of zidovudine and its intermediate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20070117 Termination date: 20101203 |