CN116199625A - 一种烟酸酯类化合物的制备方法 - Google Patents
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- 235000001968 nicotinic acid Nutrition 0.000 title claims abstract description 46
- 229960003512 nicotinic acid Drugs 0.000 title claims abstract description 46
- 239000011664 nicotinic acid Substances 0.000 title claims abstract description 45
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- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
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- 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
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/803—Processes of preparation
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Abstract
本发明公开了一种烟酸酯类化合物的制备方法,涉及化工技术领域,该制备方法包括如下具体步骤:S1、选取反应器后,将定量的3‑氰基吡啶溶于化合物A中;S2、调节温度后,往反应器中通入有机反应物;S3、监控至3‑氰基吡啶反应完全后加入有机溶剂,并用溶剂B调PH至中性;S4、在反应器中分层,使用试剂C进行萃取,合并有机相;S5、浓缩至干后得到烟酸酯类化合物;其技术要点为:利用盐酸气或氯化氢的有机溶剂,使3‑氰基吡啶与羟基化合物直接反应生成烟酸酯类化合物;整体的制备方法相较于传统的方式收率高、反应条件温和、易规模化生产,该方法中的原料来源广泛、价格低廉,从而降低了对于烟酸酯类化合物制备的生产成本。
Description
技术领域
本发明涉及化工技术领域,特别涉及一种烟酸酯类化合物的制备方法。
背景技术
烟酸酯类化合物在医药、农药及日化领域有着广泛的应用,其即可作为医药中间体使用,也可作为(皮肤)发红剂和血管扩张剂等直接使用。
现有文献报道的烟酸酯类化合物合成方法,主要有以下几种:
例1:以烟酸和乙醇为原料,在浓硫酸作用下,反应生成烟酸乙酯。
例2:以烟酸和N,N-二甲基甲酰胺二乙基缩醛为原料,在二氯甲烷中,反应生成烟酸乙酯。
例3:以烟酸和硫酸二乙酯为原料,在溴化四丁基铵作用下,反应生成烟酸乙酯。
例4:以烟酸和溴乙烷为原料,在溴化四丁基铵作用下,反应生成烟酸乙酯。
例5:先将烟酸转化成烟酰氯,再和乙醇反应生成烟酸乙酯。
以上文献中,均以烟酸为原料制备烟酸乙酯,而烟酸目前工业上主要以氨氧化法制备,该法以3-甲基吡啶或MEP为原料,在催化剂床层中与氨和氧气按一定比例进行气固相催化氧化,生成3-氰基吡啶,水解纯化得到烟酸;
也有相关文献报道,以3-氰基吡啶为原料,制备烟酸酯类化合物。
例6:以3-氰基吡啶和乙醇为原料,在三氯化铁作用下,回流21小时,反应生成烟酸乙酯。
例7:以3-氰基吡啶和乙醇为原料,在三氟化硼-乙醚作用下,回流6天,反应生成烟酸乙酯。
例8:以3-氰基吡啶和乙醇为原料,在二氧化钛作用下,反应生成烟酸乙酯。该反应收率文献报道只有11%,且含有7%的烟酰胺。
上述文献选用比烟酸更廉价的3-氰基吡啶为原料制备烟酸乙酯,但存在试剂较贵,反应时间长,温度高,三废大以及收率低的问题,导致上述方法均难以实现工业化。
发明内容
解决的技术问题:
针对现有技术的不足,本发明提供了一种成本低,反应温和,三废少,收率高,易工业化的制备烟酸酯类化合物的方法。
为实现以上目的,本发明通过以下技术方案予以实现:
其中R为1-20个C的直链或支链烷烃、苄基或苯环上部份氢被卤素、硝基或氨基取代的苄基;3-氰基吡啶与羟基化合物在盐酸气或氯化氢的有机溶剂作用下,反应生成烟酸酯类化合物。
上述的R可为甲基,乙基,苄基,正十二烷基和正十八烷基。
该烟酸酯类化合物的制备方法,包括如下具体步骤:
S1、选取反应器后,将定量的3-氰基吡啶溶于化合物A中;
其中,当3-氰基吡啶为:5X时,化合物A的选取范围为:1~100X;
化合物A包括羟基化合物;
S2、调节温度后,往反应器中通入有机反应物;
其中,调节温度时使用到温度调节器,根据具体化合物A的种类,对反应器内的温度进行降低或升高,且温度调节的范围为:-20℃~80℃;
有机反应物包含盐酸气和含氯化氢的有机溶剂中的任意一种或二者混合;
S3、监控至3-氰基吡啶反应完全后加入有机溶剂,并用溶剂B调PH至中性;
其中,监控3-氰基吡啶反应程度时使用到TLC监控系统,该TLC监控系统用于判断3-氰基吡啶是否反应完全;
溶剂B为碱溶液,且调PH的具体步骤如下:
首先,选取干净的滴管,并抽取碱溶液;
然后,将滴管内的碱溶液匀速的滴入反应器中;
最后,在滴入反应器的同时使用搅拌器完成搅拌,直至反应器内的PH达到中性即可;
S4、在反应器中分层,使用试剂C进行萃取,合并有机相;
其中,在反应器中分层即为静置处理,静置时长为:10mi n~60mi n,直至出现明显的分层现象即可;
进行萃取时使用的试剂C包括二氯甲烷和2-甲基四氢呋喃等与水不互溶的有机溶剂;
S5、浓缩至干后得到烟酸酯类化合物;
其中,进行浓缩至干时采用减压浓缩和常压浓缩中的任意一种。
另外的,一种化合物烟酸乙酯的制备方法,该制备反应式为:
3-氰基吡啶与乙醇在盐酸气或氯化氢的有机溶剂作用下,反应生成烟酸乙酯。
一种化合物烟酸甲酯的制备方法,该制备反应式为:
3-氰基吡啶与甲醇在盐酸气或氯化氢的有机溶剂作用下,反应生成烟酸甲酯。
有益效果:
本发明开创性地利用盐酸气或氯化氢的有机溶剂,使3-氰基吡啶与羟基化合物直接反应生成烟酸酯类化合物,得到的烟酸酯类化合物收率大于90%;
整体的制备方法相较于传统的方式收率高、反应条件温和、易规模化生产,同时,该方法中的原料来源广泛、价格低廉,从而降低了对于烟酸酯类化合物制备的生产成本。
附图说明
上述说明仅是本发明技术方案的概述,为了能够更清楚了解本发明的技术手段,并可依照说明书的内容予以实施,以下以本发明的较佳实施例并配合附图详细说明如后。
图1为本发明整个制备流程示意图。
具体实施方式
本申请实施例通过提供一种烟酸酯类化合物的制备方法,用盐酸气或氯化氢的有机溶剂,使3-氰基吡啶与羟基化合物直接反应生成烟酸酯类化合物,得到的烟酸酯类化合物收率大于90%;整体的制备方法相较于传统的方式收率高、反应条件温和、易规模化生产
本申请实施例中的技术方案为解决上述背景技术的问题,参考图1所示,总体思路如下(注:除非另有说明,以下实施例中使用的原料和试剂均为市售商品,或者可以通过已知方法制备):
实施例1:
关于烟酸甲酯制备的具体步骤:
S1、将10g 3-氰基吡啶溶于50mL甲醇中;
S2、降温至0-5℃,往反应器中通入适量盐酸气;
S3、使用TLC监控至3-氰基吡啶反应完全,加入二氯甲烷,用饱和无机碱溶液调pH至中性;
S4、分层后用二氯甲烷萃取两次,合并有机相;
S5、浓缩至干,得烟酸甲酯12.5g,收率为:95.2%。
实施例2:
关于烟酸乙酯制备的具体步骤:
S1、将15g 3-氰基吡啶溶于150mL乙醇中;
S2、升温至40-55℃,往反应器中通入适量盐酸气;
S3、使用TLC监控至3-氰基吡啶反应完全,加入二氯甲烷,用饱和碳酸氢钠溶液调pH至中性;
S4、分层后用二氯甲烷萃取两次,合并有机相;
S5、浓缩至干,得烟酸乙酯20.6g,收率为:94.8%。
实施例3:
关于烟酸苄酯制备的具体步骤:
S1、将15g 3-氰基吡啶溶于150mL二氯甲烷中;
S2、升温至30-40℃,往反应器中通入适量盐酸气;
S3、使用TLC监控至3-氰基吡啶反应完全,加入二氯甲烷,用饱和氢氧化钠溶液调pH至中性;
S4、分层后用二氯甲烷萃取两次,合并有机相;
S5、浓缩至干,得烟酸苄酯29.6g,收率为:96.5%。
实施例4:
关于烟酸正十二醇酯制备的具体步骤:
S1、将15g 3-氰基吡啶溶于150mL二氯甲烷中;
S2、升温至30-40℃,往反应器中滴加适量盐酸气乙酸乙酯溶液;
S3、使用TLC监控至3-氰基吡啶反应完全,加入二氯甲烷,用饱和无机碱溶液调pH至中性;
S4、分层后用二氯甲烷萃取两次,合并有机相;
S5、浓缩至干,得烟酸正十二醇酯39.2g,收率为:93.1%。
实施例5:
关于烟酸正十八酯制备的具体步骤:
S1、将15g 3-氰基吡啶溶于150mL2-甲基四氢呋喃中;
S2、降温至0-5℃,往反应器中通入滴加适量盐酸气,2-甲基四氢呋喃溶液;
S3、使用TLC监控至3-氰基吡啶反应完全,用饱和无机碱溶液调pH至中性;
S4、分层后用2-甲基四氢呋喃萃取两次,合并有机相;
S5、浓缩至干,得烟酸正十八酯52.1g,收率为:96.2%。
结合上述实施例1-实施例5可以得知:
本发明开创性地利用盐酸气或氯化氢的有机溶剂,使3-氰基吡啶与羟基化合物直接反应生成烟酸酯类化合物,得到的烟酸酯类化合物收率大于90%;整体的制备方法相较于传统的方式收率高、反应条件温和、易规模化生产,同时,该方法中的原料来源广泛、价格低廉,从而降低了对于烟酸酯类化合物制备的生产成本。
最后应说明的是:显然,上述实施例仅仅是为清楚地说明本发明所作的举例,而并非对实施方式的限定。对于所属领域的普通技术人员来说,在上述说明的基础上还可以做出其它不同形式的变化或变动。这里无需也无法对所有的实施方式予以穷举。而由此所引申出的显而易见的变化或变动仍处于本发明的保护范围之中。
Claims (10)
2.一种烟酸酯类化合物的制备方法,其特征在于:基于烟酸酯类化合物的制备原理,该烟酸酯类化合物的具体制备方法包括如下步骤:
S1、选取反应器后,将定量的3-氰基吡啶溶于化合物A中;
S2、调节温度后,往反应器中通入有机反应物;
S3、监控至3-氰基吡啶反应完全后加入有机溶剂,并用溶剂B调PH至中性;
S4、在反应器中分层,使用试剂C进行萃取,合并有机相;
S5、浓缩至干后得到烟酸酯类化合物。
3.如权利要求2所述的一种烟酸酯类化合物的制备方法,其特征在于:在所述S1中,
当3-氰基吡啶为:1X时,化合物A的选取范围为:1~100X。
4.如权利要求2所述的一种烟酸酯类化合物的制备方法,其特征在于:在所述S1中,
化合物A包括羟基化合物。
5.如权利要求2所述的一种烟酸酯类化合物的制备方法,其特征在于:在所述S2中,
调节温度时使用到温度调节器,根据具体化合物A的种类,对反应器内的温度进行降低或升高,且温度调节的范围为:-20℃~80℃。
6.如权利要求2所述的一种烟酸酯类化合物的制备方法,其特征在于:在所述S2中,
有机反应物包含盐酸气和含氯化氢的有机溶剂中的任意一种或二者混合。
7.如权利要求2所述的一种烟酸酯类化合物的制备方法,其特征在于:在所述S3中,
监控3-氰基吡啶反应程度时使用到TLC监控系统,该TLC监控系统用于判断3-氰基吡啶是否反应完全;
溶剂B为碱溶液,且调PH的具体步骤如下:
首先,选取干净的滴管,并抽取碱溶液;
然后,将滴管内的碱溶液匀速的滴入反应器中;
最后,在滴入反应器的同时使用搅拌器完成搅拌,直至反应器内的PH达到中性即可。
8.如权利要求2所述的一种烟酸酯类化合物的制备方法,其特征在于:在所述S4中,
在反应器中分层即为静置处理,静置时长为:10min~60min,直至出现明显的分层现象即可。
9.如权利要求2所述的一种烟酸酯类化合物的制备方法,其特征在于:在所述S4中,
进行萃取时使用的试剂C包括二氯甲烷和2-甲基四氢呋喃等与水不互溶的有机溶剂。
10.如权利要求2所述的一种烟酸酯类化合物的制备方法,其特征在于:在所述S5中,
进行浓缩至干时采用减压浓缩和常压浓缩中的任意一种。
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CN1184465A (zh) * | 1995-05-19 | 1998-06-10 | 巴斯福股份公司 | 羧酸衍生物的制备 |
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CN1184465A (zh) * | 1995-05-19 | 1998-06-10 | 巴斯福股份公司 | 羧酸衍生物的制备 |
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