CN101643393A - 2-甲氧基-4-羟基氯苯的制备方法 - Google Patents

2-甲氧基-4-羟基氯苯的制备方法 Download PDF

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CN101643393A
CN101643393A CN200810139131A CN200810139131A CN101643393A CN 101643393 A CN101643393 A CN 101643393A CN 200810139131 A CN200810139131 A CN 200810139131A CN 200810139131 A CN200810139131 A CN 200810139131A CN 101643393 A CN101643393 A CN 101643393A
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organic phase
reaction
methoxyl
solvent
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夏恩将
夏恩胜
岳岩
夏念丰
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Abstract

本发明公开了一种2－甲氧基－4－羟基氯苯的制备方法，在对氯苯酚及溶剂存在下进行溴化反应，所得产物再经过甲氧基化反应生成2－甲氧基－4－羟基氯苯成品。该制备方法工艺路线合理，先进可行。工艺过程中所用有机溶剂全部回收套用。所制得的2－甲氧基－4－羟基氯苯收率大、纯度高。

Description

2-甲氧基-4-羟基氯苯的制备方法
技术领域
本发明涉及一种2-甲氧基-4-羟基氯苯的制备方法。
背景技术
2-甲氧基-4-羟基氯苯为医药中间体，具有较大的工业化前景。
发明内容
本发明的目的就是提供一种2-甲氧基-4-羟基氯苯的制备方法，为达到以上目的，本发明所采取的技术方案为：
2-甲氧基-4-羟基氯苯由以下步骤制备而成：
1)向20L反应瓶加入对氯苯酚、氯仿，20～30℃搅拌5分钟。滴加Br2，滴加速度控制在Br2滴加进去颜色马上消失为宜。20～30℃反应，反应过程有大量HBr产生，须有尾气吸收装置。Br2滴加完毕后反应30min取样分析。反应完全后加水洗有机层，分液，再洗两次至PH＝7，氯仿层无水Na2SO4干燥，过滤，减压蒸除氯仿，得油状物6.5kg，收率大于95％。
甲氧基化反应：
2)向5L配回流装置的反应瓶中加入邻溴对氯苯酚、二甲苯、甲醇、吡啶、碳酸二甲酯，搅拌均匀。反应瓶在冰水浴冷却下，慢慢加入甲醇钠，控制加入速度，内温不超过90℃以防冲料。加完后升温回流1h，取样分析。反应结束后，用水分次萃取有机相，合并水层，浓HCl调PH，有油层析出，分出油层，水层用乙酸乙酯萃取三次，合并有机相，用饱和盐水洗至PH＝6-7。减压蒸除溶剂，得粗品精馏，收集4mmHg，125℃的馏分。GC 99.2％。
具体实施方式
下面结合实施例对本发明做详细说明：
a.溴化反应：
在20L反应瓶加入3.5kg对氯苯酚，氯仿5L，20～30℃搅拌5分钟。滴加6.4kgBr2，。20～30℃反应，反应过程有大量HBr产生，须有尾气吸收装置。Br2滴加完毕后反应30min取样分析。反应完全后加水洗有机层，分液，再洗两次至PH＝7，氯仿层干燥，过滤，减压蒸除氯仿，得油状物6.5kg，收率大于95％。
B.甲氧基化反应：
向5L配回流装置的反应瓶中加入邻溴对氯苯酚252.5g，二甲苯1250ml，甲醇502ml，吡啶95ml，碳酸二甲酯120ml，搅拌均匀。反应瓶在冰水浴冷却下，慢慢加入甲醇钠450g，控制加入速度，内温不超过90℃以防冲料。加完后升温回流1h，取样分析。反应结束后，3000ml水分次萃取有机相，合并水层，浓HCl调PH＝3-5，有油层析出，分出油层，水层用乙酸乙酯萃取三次，合并有机相，用饱和盐水洗至PH＝6-7。减压蒸除溶剂，得粗品精馏，收集4mmHg，125℃的馏分。GC 99.2％。

Claims (1)

1、一种2-甲氧基-4-羟基氯苯的制备方法，其特征在于由以下步骤制备而成：
在反应釜中加入对氯苯酚及溶剂氯仿，搅拌均匀后，保持温度在20～40℃进行溴化反应，反应产物在溶剂存下，加入吡啶、碳酸二甲脂，然后保持0～5℃慢慢加入甲醇钠，加完后升温回流1h，取样分析。反应结束后，用水分次萃取有机相，合并水层，浓HCl调PH，分出油层，水层用乙酸乙酯萃取三次，合并有机相，用饱和盐水洗至PH＝6-7。减压蒸除溶剂，得粗品精馏，收集4mmHg，125℃的馏分。GC 99.2％。
CN200810139131A 2008-08-08 2008-08-08 2-甲氧基-4-羟基氯苯的制备方法 Pending CN101643393A (zh)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102958913A (zh) * 2010-05-19 2013-03-06 罗地亚（中国）投资有限公司 制备邻位取代的5-卤代酚及其合成中间体的方法
CN103864588A (zh) * 2014-03-25 2014-06-18 河北工业大学 一种2,3-二甲氧基苯甲醛的制备方法

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102958913A (zh) * 2010-05-19 2013-03-06 罗地亚（中国）投资有限公司 制备邻位取代的5-卤代酚及其合成中间体的方法
CN102958913B (zh) * 2010-05-19 2015-11-25 罗地亚（中国）投资有限公司 制备邻位取代的5-卤代酚及其合成中间体的方法
CN103864588A (zh) * 2014-03-25 2014-06-18 河北工业大学 一种2,3-二甲氧基苯甲醛的制备方法
CN103864588B (zh) * 2014-03-25 2015-09-09 河北工业大学 一种2,3-二甲氧基苯甲醛的制备方法

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