CN111004174A - 一种紫外光催化制备5-溴甲基-2,3-吡啶二甲酸二甲酯的方法 - Google Patents
一种紫外光催化制备5-溴甲基-2,3-吡啶二甲酸二甲酯的方法 Download PDFInfo
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- 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
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Abstract
本发明涉及中间体化合物的制备,具体的说是一种紫外光催化制备5‑溴甲基‑2,3‑吡啶二甲酸二甲酯的方法。以5‑甲基‑2,3‑吡啶二甲酸二甲酯为起始原料,在有机溶剂中在紫外光的催化引发下经溴化反应制得5‑溴甲基‑2,3‑吡啶二甲酸二甲酯。本发明采用紫外光作为催化引发作用,能够提高原料的转化率,转化率最高至90%。本发明在紫外光的催化引发下反应,具有较高的选择性,在转化率达到90%时,仅产生5%的二溴产物。
Description
技术领域
本发明涉及中间体化合物的制备,具体的说是一种紫外光催化制备5-溴甲基-2,3-吡啶二甲酸二甲酯的方法。
背景技术
5-溴甲基-2,3-吡啶二甲酸二甲酯是制备甲氧咪草烟的关键中间体,目前已公开的资料说明其合成方法主要以5-甲基-2,3-吡啶二甲酸二甲酯为原料,经卤化制得目标产品。如US2011224433、EP0747360、US5288866等。
专利US5288866A和WO2010055042A1都公开了5-溴甲基-2,3-吡啶二甲酸二甲酯的制备方法,以5-甲基-2,3-吡啶二甲酸二甲酯为起始原料,在偶氮二异丁腈的存在下在有机溶剂中、经NBS或次溴酸钠溴化制得,但专利中同时报道了溴化过程会有二溴产物生成,且二溴副产物在产品中的比例超过20%。
专利CN107216286A公开了一种5-溴甲基-2,3-吡啶二甲酸二甲酯的制备方法,以5-甲基-2,3-吡啶二甲酸二甲酯为起始原料,偶氮二异丁腈和溴酸钠为催化剂,在有机溶剂中、经氢溴酸溴化制得,反应条件为回流。虽然能够控制二溴产物的生成,但是反应的转化率较低,原料剩余超过30%,且氢溴酸投料量是5-溴甲基-2,3-吡啶二甲酸二甲酯的二倍,原料过量较多。
综上现有报道中的溴化方法在原料转化率和杂质控制方面存在不足,未反应完全的原料和生成的二溴副产物都会给原药的提纯和质量控制带来困难。
发明内容
本发明目的在于提供一种紫外光催化制备5-溴甲基-2,3-吡啶二甲酸二甲酯的方法。
为实现上述目的,本发明采用技术方案为:
一种紫外光催化制备5-溴甲基-2,3-吡啶二甲酸二甲酯的方法,以5-甲基-2,3-吡啶二甲酸二甲酯为起始原料,在有机溶剂中在紫外光的催化引发下经溴化反应制得5-溴甲基-2,3-吡啶二甲酸二甲酯。
反应式如下:
将5-甲基-2,3-吡啶二甲酸二甲酯溶于有机溶剂中,在10~400nm的紫外光照射下、于55~90℃下加入溴化试剂,而后于65~90℃下保温反应0.5~1小时,得到5-溴甲基-2,3-吡啶二甲酸二甲酯。
所述5-甲基-2,3-吡啶二甲酸二甲酯与所述溴化试剂的摩尔比为1:0.7~1:1。
溴化试剂在2~4小时内加入至反应体系内。
所述紫外光为指波长为300~350nm的紫外光。
所述溴化试剂加入温度为70~85℃;保温反应温度为70~85℃。
所述有机溶剂为氯代烃;其中,氯代烃选自1,2-二氯乙烷、氯苯、二氯苯或三氯甲烷;所述氯代烃与5-甲基-2,3-吡啶二甲酸二甲酯的摩尔比为1:5~1:10。
所述溴化试剂选自N-溴代琥珀酰亚胺、二溴海因、次溴酸钠、溴酸钠、溴素或次溴酸。
针对现有的技术,本发明所具有的优点:
本发明催化合成5-溴甲基-2,3-吡啶二甲酸二甲酯的方法,以5-甲基-2,3-吡啶二甲酸二甲酯为原料,经溴化试剂、卤代烷存在下,紫外光作为催化媒介催化制备5-溴甲基-2,3-吡啶二甲酸二甲酯;具体为
(1)本发明采用紫外光作为催化引发作用,能够提高原料的转化率,转化率最高至90%。
(2)本发明在紫外光的催化引发下反应,具有较高的选择性,在转化率达到90%时,仅产生5%的二溴产物。
具体实施方式
以下结合实例对本发明的具体实施方式做进一步说明,应当指出的是,此处所描述的具体实施方式只是为了说明和解释本发明,并不局限于本发明。
实施例1
向能透过紫外光的反应器中加入4.1g的5-甲基-2,3-吡啶二甲酸二甲酯(0.0196mol)、55g的1,2-二氯乙烷,加热至70℃,开启紫外灯,让反应器在紫外灯灯光辐射范围内,将2.7g的N-溴代琥珀酰亚胺(0.0152mol)投入瓶中,约2小时加完,投完料后升温至85℃,保温1小时。HPLC检测剩余23%的5-甲基-2,3-吡啶二甲酸二甲酯,二溴副产物2%。
实施例2
向能透过紫外光的反应器中加入4.1g的5-甲基-2,3-吡啶二甲酸二甲酯(0.0196mol)、100g的氯苯,加热至85℃,开启紫外灯,让反应器在紫外灯灯光辐射范围内,将4.18g的次溴酸(0.0215mol)滴加入瓶中,约3小时加完,投完料后保持85℃,保温0.5小时。HPLC检测剩余8%的5-甲基-2,3-吡啶二甲酸二甲酯,二溴副产物5%。
实施例3
向能透过紫外光的反应器中加入4.1g的5-甲基-2,3-吡啶二甲酸二甲酯(0.0196mol)、120g的三氯甲烷,加热至55℃,开启紫外灯,让反应器在紫外灯灯光辐射范围内,将5.6g的二溴海因(0.0182mol)投入瓶中,约4小时加完,投完料后保持65℃,保温0.5小时。HPLC检测剩余12%的5-甲基-2,3-吡啶二甲酸二甲酯,二溴副产物3%。
实施例4
向能透过紫外光的反应器中加入4.1g的5-甲基-2,3-吡啶二甲酸二甲酯(0.0196mol)、100g的二氯苯,加热至75℃,开启紫外灯,让反应器在紫外灯灯光辐射范围内,将2.5g的溴酸钠(0.0166mol)投入瓶中,约3小时加完,投完料后保持85℃,保温0.5小时。HPLC检测剩余20%的5-甲基-2,3-吡啶二甲酸二甲酯,二溴副产物3%。
Claims (8)
1.一种紫外光催化制备5-溴甲基-2,3-吡啶二甲酸二甲酯的方法,其特征在于:以5-甲基-2,3-吡啶二甲酸二甲酯为起始原料,在有机溶剂中在紫外光的催化引发下经溴化反应制得5-溴甲基-2,3-吡啶二甲酸二甲酯。
3.按权利要求2所述的紫外光催化制备5-溴甲基-2,3-吡啶二甲酸二甲酯的方法,其特征在于:所述5-甲基-2,3-吡啶二甲酸二甲酯与所述溴化试剂的摩尔比为1:0.7~1:1。
4.按权利要求2所述的紫外光催化制备5-溴甲基-2,3-吡啶二甲酸二甲酯的方法,其特征在于:溴化试剂在2~4小时内加入至反应体系内。
5.按权利要求2所述的紫外光催化制备5-溴甲基-2,3-吡啶二甲酸二甲酯的方法,其特征在于:所述紫外光为指波长为300~350nm的紫外光。
6.按权利要求2所述的紫外光催化制备5-溴甲基-2,3-吡啶二甲酸二甲酯的方法,其特征在于:所述溴化试剂加入温度为70~85℃;保温反应温度为70~85℃。
7.按权利要求2所述的紫外光催化制备5-溴甲基-2,3-吡啶二甲酸二甲酯的方法,其特征在于:所述有机溶剂为氯代烃;其中,氯代烃选自1,2-二氯乙烷、氯苯、二氯苯或三氯甲烷;所述氯代烃与5-甲基-2,3-吡啶二甲酸二甲酯的摩尔比为1:5~1:10。
8.按权利要求2所述的紫外光催化制备5-溴甲基-2,3-吡啶二甲酸二甲酯的方法,其特征在于:所述溴化试剂选自N-溴代琥珀酰亚胺、二溴海因、次溴酸钠、溴酸钠、溴素或次溴酸。
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