CN106905229A - 邻位烷氧基取代吡啶的新合成方法 - Google Patents

邻位烷氧基取代吡啶的新合成方法 Download PDF

Info

Publication number
CN106905229A
CN106905229A CN201710131807.2A CN201710131807A CN106905229A CN 106905229 A CN106905229 A CN 106905229A CN 201710131807 A CN201710131807 A CN 201710131807A CN 106905229 A CN106905229 A CN 106905229A
Authority
CN
China
Prior art keywords
ortho
pyridines
alkoxy
alkoxy substituted
novel synthesis
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.)
Pending
Application number
CN201710131807.2A
Other languages
English (en)
Inventor
王有名
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Huaihua Jin Xin New Material Co Ltd
Original Assignee
Huaihua Jin Xin New Material Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Huaihua Jin Xin New Material Co Ltd filed Critical Huaihua Jin Xin New Material Co Ltd
Priority to CN201710131807.2A priority Critical patent/CN106905229A/zh
Publication of CN106905229A publication Critical patent/CN106905229A/zh
Pending legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/69—Two or more oxygen atoms

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pyridine Compounds (AREA)

Abstract

本发明涉及邻位烷氧基取代吡啶的新合成方法。采用邻位卤代吡啶为原料，在氢氧化钠的作用下与相应的醇反应得到邻位烷氧基取代吡啶。该反应对邻位卤代吡啶具有通用性，方法简单而又实用。考察了反应中氢氧化钠的用量对单取代和双取代的影响，实现了烷氧基单取代和烷氧基双取代的产物，提供了一条操作简单，经济实惠的合成邻位烷氧基吡啶全新工艺。

Description

邻位烷氧基取代吡啶的新合成方法
技术领域
本发明属于化合物合成领域中一种邻位烷氧基取代吡啶的新合成方法。
背景技术
吡啶类化合物具有广泛的生物活性，吡啶类化合物作为农药或医药的品种也不少，取代吡啶化合物的生物活性的研究引起了科学家们极大的兴趣，相关的报道层出不穷。
近年来，吡啶邻位上烷氧基取代的吡啶化合物的报道越来越多，合成邻位烷氧基取代吡啶化合物变得越来越重要。通常采用邻位卤代吡啶与相应的醇钠反应，该反应时间长，杂质多，我们采取邻位卤代吡啶与相应的醇反应，开发了一条简捷而又经济实惠的合成路线，反应的收率高，杂质少，产品很容易分离。
发明内容
本发明的目的在于提供一种邻位烷氧基吡啶的制备方法，本发明提供了新的反应路线，反应温度、反应物料比，由此提供一种更加实用、成本更低的邻位烷氧基吡啶的生产工艺。
本发明解决其技术问题是采取以下技术方案实现的：
一种邻位烷氧基取代吡啶的新合成方法，涉及产物的结构式为：
进一步，采用邻位卤代吡啶为起始原料，在固体氢氧化钠的作用下与相应的醇反应得到单取代烷氧基吡啶或者双取代烷氧基吡啶。
进一步，邻位卤代吡啶为氟取代，氯取代，溴取代或者碘取代。
进一步，相应的醇为甲醇，乙醇和丙醇等。
进一步，单取代烷氧基吡啶的生产中氢氧化钠的用量为1个当量；双取代烷氧基吡啶的生产中氢氧化钠的用量为2.5个当量。
进一步，邻位烷氧基吡啶的生产中的反应条件为回流反应。
进一步，邻位烷氧基吡啶的生产中的反应时间为4-8小时。
本发明的优点和积极效果是：
1、本发明使用邻位卤素取代吡啶为原料，在氢氧化钠的作用下与相应的醇反应得到得到邻位烷氧基取代吡啶。该反应操作简单，产率高，产品容易分离。
2、本发明通过对反应原料和条件的改变，适用于邻位卤素取代的吡啶化合物，提供了一条简捷而又经济实惠的生产工艺。
具体实施方式
下面结合具体实施例对本发明作进一步详述。
本发明制备邻位烷氧基取代吡啶的合成化学式如下：
表一 不同的烷氧基取代的吡啶化合物
原料 产物 收率(％) B.p./M.p.(℃)
2-溴吡啶 2-甲氧基吡啶 98 142-143
2-氯吡啶 2-甲氧基吡啶 95 142-143
2-溴吡啶 2-乙氧基吡啶 93 155-156
2，6-二氯吡啶 2-甲氧基-6-氯吡啶 88 185-186
2，6-二氯吡啶 2-乙氧基-6-氯吡啶 85 207-208
2，6-二溴吡啶 2-甲氧基-6-溴吡啶 98 206-207
2，6-二溴吡啶 2-乙氧基-6-溴吡啶 93 224-225
2，5-二溴吡啶 2-甲氧基-5-溴吡啶 98 197-198
2，5-二溴吡啶 2-乙氧基-5-溴吡啶 95 33-35(M.p.)
2，6-二溴吡啶 2，6-二甲氧基吡啶 94 178-180
2，6-二氟吡啶 2-甲氧基-6-氟吡啶 86 141-142
2，4-二氯吡啶 2-甲氧基-4-氯吡啶 85 177-178
2，6-二氯吡啶 2，6-二乙氧基吡啶 86 220-222
实施例1
在500毫升的反应瓶中，加入29.6g2，6-二氯吡啶，8g固体氢氧化钠和200毫升甲醇，搅拌下开始升温至回流状态，反应时间为8小时，停止反应，蒸出大部分甲醇，冷却，加入100毫升水，用二氯甲烷提取一次，脱出二氯甲烷得到粗产品，将粗产品进行减压蒸馏得到2-甲氧基-6-氯吡啶，产率为88％。
实施例2
(1)在500毫升的反应瓶中，加入47g2，6-二溴吡啶，8g固体氢氧化钠和200毫升乙醇，搅拌下开始升温至回流状态，反应时间为6小时，停止反应，蒸出大部分乙醇，冷却，加入100毫升水，用二氯甲烷提取一次，脱出二氯甲烷得到粗产品，将粗产品进行减压蒸馏得到2-乙氧基-6-溴吡啶，产率为93％。
实施例3
(1)在500毫升的反应瓶中，加入47g2，5-二溴吡啶，8g固体氢氧化钠和200毫升甲醇，搅拌下开始升温至回流状态，反应时间为5小时，停止反应，蒸出大部分甲醇，冷却，加入100毫升水，用二氯甲烷提取一次，脱出二氯甲烷得到粗产品，将粗产品进行减压蒸馏得到2-甲氧基-5-溴吡啶，产率为98％。
实施例4
(1)在500毫升的反应瓶中，加入29.6g2，6-二氯吡啶，16g固体氢氧化钠和200毫升甲醇，搅拌下开始升温至回流状态，反应时间为8小时，停止反应，蒸出大部分甲醇，冷却，加入100毫升水，用二氯甲烷提取一次，脱出二氯甲烷得到粗产品，将粗产品进行减压蒸馏得到2，6-二甲氧基吡啶，产率为94％。
以上所述仅为本发明的较佳实施例而已，并不用以限制本发明，凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。

Claims (7)

1.邻位烷氧基取代吡啶的新合成方法，其特征在于：涉及产物的结构式为：
。
2.根据权利要求1所述的邻位烷氧基取代吡啶的新合成方法，其特征在于：采用邻位卤代吡啶为起始原料，在固体氢氧化钠的作用下与相应的醇反应得到单取代烷氧基吡啶或者双取代烷氧基吡啶。
3.根据权利要求2所述的邻位烷氧基取代吡啶的新合成方法，其特征在于：邻位卤代吡啶为氟取代，氯取代，溴取代或者碘取代。
4.根据权利要求2所述的邻位烷氧基取代吡啶的新合成方法，其特征在于：相应的醇为甲醇，乙醇和丙醇等。
5.根据权利要求2所述的邻位烷氧基取代吡啶的新合成方法，其特征在于：单取代烷氧基吡啶的生产中氢氧化钠的用量为1个当量；双取代烷氧基吡啶的生产中氢氧化钠的用量为2.5个当量。
6.根据权利要求2所述的邻位烷氧基取代吡啶的新合成方法，其特征在于：邻位烷氧基吡啶的生产中的反应条件为回流反应。
7.根据权利要求2所述的邻位烷氧基取代吡啶的新合成方法，其特征在于：邻位烷氧基吡啶的生产中的反应时间为4-8小时。
CN201710131807.2A 2017-03-07 2017-03-07 邻位烷氧基取代吡啶的新合成方法 Pending CN106905229A (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710131807.2A CN106905229A (zh) 2017-03-07 2017-03-07 邻位烷氧基取代吡啶的新合成方法

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710131807.2A CN106905229A (zh) 2017-03-07 2017-03-07 邻位烷氧基取代吡啶的新合成方法

Publications (1)

Publication Number Publication Date
CN106905229A true CN106905229A (zh) 2017-06-30

Family

ID=59186898

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710131807.2A Pending CN106905229A (zh) 2017-03-07 2017-03-07 邻位烷氧基取代吡啶的新合成方法

Country Status (1)

Country Link
CN (1) CN106905229A (zh)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107935922A (zh) * 2017-12-07 2018-04-20 山东昆达生物科技有限公司 一种6‑氯‑2‑烃氧基吡啶的合成方法及后处理工艺

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102452978A (zh) * 2010-11-01 2012-05-16 重庆康丁医药技术有限公司 2-氯-取代或未取代脂族烃氧基吡啶及其制备方法
CN104725302A (zh) * 2015-03-23 2015-06-24 河南师范大学 一种利拉萘酯的制备方法

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102452978A (zh) * 2010-11-01 2012-05-16 重庆康丁医药技术有限公司 2-氯-取代或未取代脂族烃氧基吡啶及其制备方法
CN104725302A (zh) * 2015-03-23 2015-06-24 河南师范大学 一种利拉萘酯的制备方法

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
QUAN LIU等: "Efficient Synthesis of Unsymmetrical Heteroaryl Ethers by a Transition Metal-Free C－O Cross-Coupling Reaction of Activated and Unactivated Heteroaryl Chlorides with Alcohols and Phenols", 《CHIN. J. CHEM.》 *
刘洁等: "烷氧基卤代吡啶及其二苯基膦衍生物的合成研究", 《化学试剂》 *
石庆东等: "利拉萘酯合成工艺改进", 《广州化工》 *
阎峰等: "2-巯基-5-甲氧基咪唑并[4,5-b]吡啶的合成及表征", 《精细化工》 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107935922A (zh) * 2017-12-07 2018-04-20 山东昆达生物科技有限公司 一种6‑氯‑2‑烃氧基吡啶的合成方法及后处理工艺

Similar Documents

Publication Publication Date Title
CN107936029B (zh) 一种合成瑞博西尼的方法
CN104177292A (zh) 一种工业化生产甲苯磺酸索拉非尼多晶型ⅰ的方法
CN102079737B (zh) 一种制备芹菜素的方法
CN107129499A (zh) 含咪唑环的稠杂环类化合物及其制备方法和应用
CN108467396A (zh) 一种更昔洛韦的制备方法
CN106905229A (zh) 邻位烷氧基取代吡啶的新合成方法
CN104004006B (zh) 一种3,6-二氢-2h-吡喃-4-硼酸频哪醇酯的合成方法
CN109956871B (zh) 一种3,4,5-三氟-2’-硝基联苯的制备方法
CN110845401A (zh) 一种2-氟-3,6-二羟基吡啶的合成方法
CN107324964B (zh) 一种联苯类衍生物的合成方法
CN108530476A (zh) 一种克立硼罗中间体的制备方法
CN105949196B (zh) 一种mer/flt3双重抑制剂中间体的制备方法
CN106496055A (zh) 一种抗心衰新药的关键组分沙库比曲的新合成方法
CN101525310B (zh) 1-苯甲酰基-3-(2-羟基-1，1-二甲基乙基)硫脲的合成方法
CN106866547B (zh) 2-乙氧基-4,6-二氯嘧啶的合成方法
CN106916148B (zh) 一种合成依匹哌唑的方法
CN106883185B (zh) 一种4-氯-2-三氟甲基嘧啶的制备方法
CN104177290A (zh) 一种3,5,6-三氯吡啶-2-醇钠的新的合成工艺
CN107382640A (zh) β‑芳基苯丙酮类化合物的合成方法
CN107200708A (zh) 一种维莫德吉的制备方法
CN108752339B (zh) 一种喹叨啉及其衍生物的合成方法
CN106496095A (zh) 一种非天然色氨酸衍生物的合成方法
CN112266360B (zh) 一种高纯度组胺二盐酸盐的合成方法
CN109384708B (zh) 一种Akt抑制剂中间体SM1及其制备方法
CN102993022A (zh) 溴代苯胺的制备方法

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication

Application publication date: 20170630

RJ01 Rejection of invention patent application after publication