CN102731316B - 一种1，2-n，n`二甲基环己二胺的生产方法 - Google Patents
一种1，2-n，n`二甲基环己二胺的生产方法 Download PDFInfo
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- SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 claims abstract description 5
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- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 claims description 6
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 5
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- 235000011149 sulphuric acid Nutrition 0.000 abstract 1
- 239000001117 sulphuric acid Substances 0.000 abstract 1
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Abstract
本发明公开了一种1，2-N，N`二甲基环己二胺的生产方法，将邻苯二胺和芳苯磺酰氯先进行N单保护，然后利用碘甲烷或硫酸二甲酯进行N甲基化反应，在硫酸将1，2-环己二胺和芳苯磺酰氯先进行N单保护，然后利用碘甲烷或硫酸二甲酯进行N甲基化反应，在硫酸存在下水解反应去除芳苯磺酰基，得到目标产品1，2-N，N`二甲基环己二胺。本发明工艺简单，易操作，可以得到更高纯度的目标产品。
Description
技术领域
本发明涉及一种1，2-N，N`二甲基环己二胺的生产方法。
背景技术
现有的1，2-N，N`二甲基环己二胺的生产方法，如：Journal of the American Chemical Society, 124(39), 11684-11688; 2002是以环己二胺和氯甲酸酯反应或甲酸酯反应，然后用氢化铝锂还原反应，原料不但价格高，而且使用氢化铝锂很危险，所得到的产品选择性不好，难分离。而我们的方法是避开强还原剂以及危险的工艺，寻找一条更加适合产业化的工艺路线，而且能得到更高纯度的目标产品。
发明内容
本发明的目的在于提供一种工艺简单，能够得到高纯度的目标产品，而且不使用强还原剂。便于产业化的合成工艺路线。
本发明的技术解决方案是：
一种1，2-N，N`二甲基环己二胺的生产方法，其特征是：将1，2-环己二胺和芳苯磺酰氯先进行N单保护，然后利用碘甲烷或硫酸二甲酯进行N甲基化反应，在硫酸存在下水解反应去除芳苯磺酰基，得到目标产品1，2-N，N`二甲基环己二胺；反应式：
将环己二胺在吡啶溶剂中或三乙胺溶剂搅拌，将上述溶液逐滴加入到对甲苯磺酰氯和吡啶的混合溶液中，滴加过程中控制温度在100以下，滴毕，置于10-100℃下下反应7h，优选10-35℃；停止反应，加入盐酸调PH，静置12-24小时，处理得到中间体3N，N`对甲苯磺酰基环己二胺，将该原料溶解与乙腈中，加入碳酸钾粉末，常温下搅拌。置于冰浴下硫酸二甲酯或碘甲烷进行甲基化反应，后处理得到中间体2；在中间体2中加入浓硫酸加热至60-150℃反应2小时，然后加入冰水，中和后乙醚萃取，后处理得到目标产品1产品含量能达到98..0%。
本发明工艺的优点：简单，易操作，产品选择性好，总收率达到30～50%。
下面结合实施例对本发明作进一步说明：
具体实施方式：
实施例1：
步骤1：环己二胺的磺化
将1，2-环己二胺（20mmol）溶于10ml吡啶中，将上述溶液逐滴加入到对甲苯磺酰氯（40mmol）的吡啶（10ml）溶液中，滴加过程中控制温度在60以下，溶液颜色由无色变为暗红色。滴毕，置于常温下反应7h，停止反应，加入15%的盐酸调PH至6-7，静置过夜，过滤，水洗（10ml*3），得到白色粉末状固体6.5g，
步骤2：甲基化
将步骤1产物（7.18mmol）溶于乙腈（60ml）中，加入碳酸钾（28.7mmol）粉末，常温下搅拌1h。置于冰浴下加入碘甲烷（28.7mmol），在冰浴下反应30min，撤去冰浴在室温下反应12h。停止反应，旋蒸除去乙腈，加入20ml水，二氯甲烷萃取（30*3），合并有机层，水洗（90*2），无水硫酸钠干燥2h，旋蒸除去溶剂，分离得到产品2.89g，
步骤3：水解
向步骤2产物（4.48mmol）中加入浓硫酸（35.84mmol），加热至80反应4h。停止反应，向反应液中加入60ml冰水，缓慢加入氢氧化钠（71.68mmol），搅拌1h，用乙醚（60ml*3）萃取，合并有机层，水洗，旋蒸除去溶剂，精馏得到产物0.35g。
Claims (1)
1.一种2-N，N`二甲基环己二胺的生产方法，是将1，2-环己二胺和芳苯磺酰氯先进行N单保护，然后利用碘甲烷或硫酸二甲酯进行N甲基化反应，在硫酸存在下水解反应去除芳苯磺酰基，得到目标产品1，2-N，N`二甲基环己二胺；其特征是：1，2-环己二胺和芳苯磺酰氯的反应具体为：将1，2-环己二胺在吡啶溶剂或三乙胺溶剂中搅拌，将上述溶液逐滴加入到对甲苯磺酰氯和吡啶的混合溶液中，滴加过程中控制温度在60℃以下，滴毕，置于常温下反应7h，停止反应；
反应式：
。
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4098904A (en) * | 1976-11-12 | 1978-07-04 | The Upjohn Company | Analgesic n-(2-aminocycloaliphatic)benzamides |
| EP0147085A2 (en) * | 1983-12-06 | 1985-07-03 | Warner-Lambert Company | Substituted trans-1.2-diaminocyclohexyl amide compounds |
| CN1438993A (zh) * | 2000-04-05 | 2003-08-27 | 第一制药株式会社 | 乙二胺衍生物 |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4098904A (en) * | 1976-11-12 | 1978-07-04 | The Upjohn Company | Analgesic n-(2-aminocycloaliphatic)benzamides |
| EP0147085A2 (en) * | 1983-12-06 | 1985-07-03 | Warner-Lambert Company | Substituted trans-1.2-diaminocyclohexyl amide compounds |
| CN1438993A (zh) * | 2000-04-05 | 2003-08-27 | 第一制药株式会社 | 乙二胺衍生物 |
Non-Patent Citations (4)
| Title |
|---|
| An efficient synthesis of tetrasubstituted cyclohexyl-1,2-diamines;Hitesh Arjan 等;《Tetrahedron Letters》;20051231;第46卷(第11期);第1922页 * |
| Contrasitive Photoreduction Pathways of Benzophenones Governed by Regiospecific Deprotonation of Imidazoline Radical Cations and Additive Effects;Eietsu Hasegawa等;《J.Org. Chem》;20051018;第70卷(第23期);附加信息 * |
| Eietsu Hasegawa等.Contrasitive Photoreduction Pathways of Benzophenones Governed by Regiospecific Deprotonation of Imidazoline Radical Cations and Additive Effects.《J.Org. Chem》.2005,第70卷(第23期),附加信息. |
| HiteshArjan等.Anefficientsynthesisoftetrasubstitutedcyclohexyl-1 2-diamines.《Tetrahedron Letters》.2005 |
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