CN116041156A - 5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法 - Google Patents
5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法 Download PDFInfo
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Abstract
本发明公开了5‑(2,4,6‑三甲苯基)‑2‑丙酰基‑3‑羟基‑2‑环己烯‑1‑酮的合成方法,以米醛为起始原料,与乙酸酯经过缩合、环合、酰化、重排得到5‑(2,4,6‑三甲苯基)‑2‑丙酰基‑3‑羟基‑2‑环己烯‑1‑酮,本发明工艺过程简单,无危险工艺,原料易得,相对于传统工艺路线避免使用大量酸、碱,生产能耗和成本较低,适宜工业化生产。
Description
技术领域
本发明属于化学合成技术领域,具体涉及5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法。
背景技术
目前,我国主要使用的除草剂有苯氧羧酸类、酰胺类、三氮苯类和磺酰脲类等,其中酰胺类和磺酰脲类除草剂对环境污染较重,在作物体内残留量大、易产生药害,所以这两类除草剂急需更新换代。
环己烯酮类除草剂可广泛用于大豆、甜菜、油菜、花生、棉花、向日葵、马铃薯、烟草等作物田,对禾本科杂草特别有效,对阔叶作物非常安全。而月亏草酮在推荐除草的剂量下,可应用于小麦和大麦田防除多种禾本科杂草如野燕麦、看麦娘、狗尾草等,从而引起人们对于开发对如水稻、小麦、大麦、善米等禾本科作物安全的环己烯酮类除草剂广泛关注。
肟草酮(tralkoxydim),化学名称为2-[1-(乙氧基亚氨基)丙基]-3羟基-5-(2,4,6-三甲苯基)环己烯-2-酮,属环己烯酮类除草剂,具有内吸传导作用,叶面施药后迅速吸收并转移至植株全身,使杂草失绿然后枯死。
其中5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮是合成肟草酮的关键中间体,目前关于它的合成方法报道不多,主要是以米醛为原料,经过缩合、环合、酯化、转位、水解、脱羧六步反应得到5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮。此工艺中需要大量酸和碱,因此探索一条安全环保的绿色工艺路线对其工业化生产具有重要意义。
5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的化学结构式如下:
发明内容
为解决上述问题,本发明公开了5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法,以米醛为起始原料,与乙酸酯经过缩合、环合、酰化、重排得到5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮,本发明工艺过程简单,无危险工艺,原料易得,相对于传统工艺路线避免使用大量酸、碱,生产能耗和成本较低,适宜工业化生产。
为达到上述目的,本发明的技术方案如下:
5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法,包括以下步骤:
(1)米醛II和乙酸酯III加入溶剂A中,再加入三乙胺,控制温度,缓慢加入四氯化钛,保温搅拌,制得化合物IV;
(2)将步骤(1)制得的化合物IV加入溶剂B中,加入丙酮V,控制温度,再加入碱,保温搅拌,滴加盐酸调节PH至3~4,制得化合物VI溶液;
(3)将步骤(2)制得的化合物VI溶液减压浓缩后加入溶剂C萃取,回流分水,再加入缚酸剂,控制温度,滴加丙酰氯VII,保温搅拌,滴加盐酸调PH至2~3,制得化合物VIII溶液;
(4)将步骤(3)制得的化合物VIII溶液水洗分层,有机相回流分水,再加入DMAP,控制温度,保温搅拌,滴加盐酸调PH至4~5,制得化合物I;
所述合成方法的总反应式如下:
作为本发明的一种改进,所述步骤(1)中,所述米醛II与乙酸酯III的摩尔比为1:1.1~1.3,所述米醛II与三乙胺的摩尔比为1:2.5~3,所述米醛II与四氯化钛的摩尔比为1:1.1~1.3,所述米醛II与溶剂A的质量比为1:6~8。
作为本发明的一种改进,所述步骤(1)中,控制温度为0~10℃,保温搅拌时间为1~5h;优选地,控制温度为0~5℃,保温搅拌的时间为3~5h。
作为本发明的一种改进,所述步骤(1)中乙酸酯III为乙酸甲酯、乙酸乙酯、乙酸丙酯、乙酸异丙酯中的任一种;优选地,乙酸酯III为乙酸甲酯、乙酸乙酯中的任一种。
作为本发明的一种改进,所述步骤(1)中溶剂A为二氯甲烷、二氯乙烷、甲苯、氯苯中的任一种;优选地,溶剂A为甲二氯甲烷、二氯乙烷中的任一种。
作为本发明的一种改进,所述步骤(2)中,所述化合物IV与丙酮V的摩尔比为1:1.5~2,所述化合物IV与碱的摩尔比为1:1.1~1.3,所述化合物IV与溶剂B的质量比为1:5~8;
作为本发明的一种改进,所述步骤(2)中控制温度为20~30℃,保温搅拌的时间为5~10h;优选地,控制温度为20~25℃,保温搅拌的时间为5~8h。
作为本发明的一种改进,所述步骤(2)中碱为叔丁醇钾、叔丁醇钠、钠氢中的任一种;优选地,碱为叔丁醇钾、叔丁醇钠中的任一种,
作为本发明的一种改进,溶剂B为四氢呋喃、乙腈、DMF中的任一种;优选地,溶剂B为四氢呋喃、乙腈中的任一种。
作为本发明的一种改进,所述步骤(3)中,所述化合物VII与步骤(2)中化合物IV的摩尔比为0.9~1:1,所述缚酸剂与步骤(2)中化合物IV的摩尔比为1.1~1.3:1,所述溶剂C与步骤(2)中化合物IV的质量比为3~5:1;
作为本发明的一种改进,所述步骤(3)中控制温度为0~10℃,保温搅拌的时间为1~5h;控制温度为0~5℃;保温搅拌的时间为1~2h。
作为本发明的一种改进,所述步骤(3)中缚酸剂为三乙胺、N,N-二异丙基乙胺、DBU、吡啶中的任一种;优选地,缚酸剂为三乙胺、吡啶中的任一种。
作为本发明的一种改进,所述步骤(3)中溶剂C为甲苯、氯苯、二甲苯中的任一种;优选地,溶剂C为甲苯、氯苯中的任一种。
作为本发明的一种改进,所述步骤(4)中,所述催化剂DMAP与步骤(2)中化合物IV的摩尔比为0.05~0.1:1;
作为本发明的一种改进,所述步骤(4)中加入催化剂后控制温度为90~100℃,保温搅拌的时间为1~5h;优选地,加入催化剂后控制温度为90~95℃;保温搅拌的时间为1~2h。
本发明的有益效果为:本发明提供的5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法反应条件温和,同时所用原材料易得,反应步骤中的中间产物无需分离提纯直接用于下步反应工艺操作简单,避免了传统工艺中使用大量盐酸和氢氧化钠带来的环境污染和设备腐蚀,生产能耗与成本较低,适宜工业化生产。
附图说明
图1为本发明的实施例1化合物IV的HNMR图谱。
图2为本发明的实施例1化合物VI的HNMR图谱。
图3为本发明的实施例1化合物VIII的HNMR图谱。
图4为本发明的实施例1化合物I的HNMR图谱。
具体实施方式
下面结合附图和具体实施方式,进一步阐明本发明,应理解下述具体实施方式仅用于说明本发明而不用于限制本发明的范围。
实施例1
(1)化合物IV的制备:
在反应瓶中依次加入二氯甲烷180g,米醛(II)30g,乙酸乙酯(III)19.6g,三乙胺51.2g,搅拌,缓慢降温至5-10℃,滴加四氯化钛42.3g,保温反应3小时,中控米醛(II)<1%,降至室温,缓慢加入水200ml,搅拌,分层,有机相再用2N盐酸200ml洗涤1次,食盐水200ml洗涤1次,有机相减压浓缩至小体积,加入正己烷50ml,搅拌析晶,过滤,烘干,得化合物(IV)34.3g,收率83%。
化合物(IV)的HNMR图谱如图1所示。
1HNMR(CDCl3,400MHz):δ7.893~7.852(d,1H),δ7.284(s,2H),δ6.106~6.065(d,1H),δ4.332~4.279(m,2H),δ2.362(s,6H),δ2.314(s,3H),δ1.396~1.360(t,3H)。
(2)化合物(VI)的制备:
在反应瓶中依次加入四氢呋喃180g,丙酮(V)12g,步骤(1)制得的化合物(IV)30g,降温至25-30℃,再分批加入叔丁醇钾17g,保温搅拌5小时,中控化合物(IV)<1%,反应结束,降温至10℃,滴加1N盐酸调PH至3-4,得到化合物(VI)溶液,直接用于下步反应。
化合物(VI)分离提纯后的HNMR图谱如图2所示。
1HNMR(DMSO,400MHz):δ6.806(s,2H),δ5.294(s,1H),δ3.711~3.644(m,1H),δ2.865(br,2H),δ2.315(s,6H),δ2.177(m,5H)。
(3)化合物(VIII)的制备:
将步骤(2)制得的化合物(VI)溶液减压浓缩回收四氢呋喃,剩余溶液中加入甲苯50g萃取2次,有机相回流分水,水分合格后,加入三乙胺15.3g,降温至5-10℃,滴加丙酰氯(VII)11.5g,保温搅拌1小时,中控合格,反应结束,加入水50ml,再用1N盐酸调PH至2-3,分层,得到化合物(VIII)甲苯溶液,直接用于下步反应。
化合物(VIII)分离提纯后的HNMR图谱如图3所示。
1HNMR(DMSO,400MHz):δ6.817(s,2H),δ7.284(s,2H),δ3.811~3.744(m,1H),δ
3.333~2.971(m,2H),δ2.564~2.508(m,2H),δ2.441~2.428(d,1H),δ2.310(s,6H),δ2.180(s,3H),δ1.096~1.059(m,3H)。
(4)化合物I的制备:
将步骤(3)制得的化合物(VIII)甲苯溶液回流分水,水分合格后,加入DMAP0.84g,搅拌,升温至95-100℃,保温搅拌1小时,中控合格,反应结束,降至室温,加入水100ml,滴加1N盐酸调PH至4-5,分层,有机相浓缩至小体积,在0-5℃搅拌析晶2小时,过滤,烘干,得产品5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮(I)27.6g,三步收率70%。
5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮(I)的HNMR图谱如图4所示。
1HNMR(CDCl3,400MHz):δ6.884(s,2H),δ3.822~3.776(m,1H),δ3.380~3.301(m,1H),δ3.172~3.095(m,3H),δ2.737~2.687(m,1H),δ2.681~2.575(m,1H),δ2.451~2.336(s,6H),δ
2.291~2.211(s,3H),δ1.201~1.135(t,3H)。
实施例2
(1)化合物IV的制备:
在反应瓶中依次加入二氯乙烷240g,米醛(II)30g,乙酸甲酯(III)19.5g,三乙胺61.4g,搅拌,缓慢降温至0-5℃,滴加四氯化钛50g,保温反应5小时,中控米醛(II)<1%,降至室温,缓慢加入水200ml,搅拌,分层,有机相再用2N盐酸200ml洗涤1次,食盐水200ml洗涤1次,有机相减压浓缩至小体积,加入正己烷50ml,搅拌析晶,过滤,烘干,得化合物(IV)35.3g,收率80%。
(2)化合物(VI)的制备:
在反应瓶中依次加入乙腈240g,丙酮(V)17g,步骤(1)制得的化合物(IV)30g,降温至20-25℃,再分批加入叔丁醇钠18.3g,保温搅拌8小时,中控化合物(IV)<1%,反应结束,降温至10℃,滴加1N盐酸调PH至3-4,得到化合物(VI)溶液,直接用于下步反应。
(3)化合物(VIII)的制备:
将步骤(2)制得的化合物(VI)溶液减压浓缩回收乙腈,剩余溶液中加入氯苯50g萃取2次,有机相回流分水,水分合格后,加入吡啶15.1g,降温至0-5℃,滴加丙酰氯(VII)13.6g,保温搅拌2小时,中控合格,反应结束,加入水50ml,再用1N盐酸调PH至2-3,分层,得到化合物(VIII)氯苯溶液,直接用于下步反应。
(4)化合物I的制备:
将步骤(3)制得的化合物(VIII)氯苯溶液回流分水,水分合格后,加入DMAP 1.8g,搅拌,升温至90-95℃,保温搅拌2小时,中控合格,反应结束,降至室温,加入水100ml,滴加1N盐酸调PH至4-5,分层,有机相浓缩至小体积,在0-5℃搅拌析晶2小时,过滤,烘干,得产品5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮(I)30.7g,三步收率73%。
需要说明的是,上述仅仅是本发明的较佳实施例,并非用来限定本发明的保护范围,对于本技术领域的普通技术人员来说,在不脱离本发明原理的前提下,在上述实施例的基础上还可以做出若干改进和润饰,这些改进和润饰均落入本发明权利要求书的保护范围之内。
Claims (10)
1.5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法,其特征在于,包括以下步骤:
(1)米醛II和乙酸酯III加入溶剂A中,再加入三乙胺,控制温度,缓慢加入四氯化钛,保温搅拌,制得化合物IV;
(2)将步骤(1)制得的化合物IV加入溶剂B中,加入丙酮V,控制温度,再加入碱,保温搅拌,滴加盐酸调节PH至3~4,制得化合物VI溶液;
(3)将步骤(2)制得的化合物VI溶液减压浓缩后加入溶剂C萃取,回流分水,再加入缚酸剂,控制温度,滴加丙酰氯VII,保温搅拌,滴加盐酸调PH至2~3,制得化合物VIII溶液;
(4)将步骤(3)制得的化合物VIII溶液水洗分层,有机相回流分水,再加入DMAP,控制温度,保温搅拌,滴加盐酸调PH至4~5,制得化合物I;
2.根据权利要求1所述的5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法,其特征在于:所述步骤(1)中,所述米醛II与乙酸酯III的摩尔比为1:1.1~1.3,所述米醛II与三乙胺的摩尔比为1:2.5~3,所述米醛II与四氯化钛的摩尔比为1:1.1~1.3,所述米醛II与溶剂A的质量比为1:6~8。
3.根据权利要求1所述的5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法,其特征在于:所述步骤(1)中,控制温度为0~10℃,保温搅拌时间为1~5h。
5.根据权利要求1所述的5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法,其特征在于:所述步骤(1)中溶剂A为二氯甲烷、二氯乙烷、甲苯、氯苯中的任一种。
6.根据权利要求1所述的5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法,其特征在于:所述步骤(2)中,所述化合物IV与丙酮V的摩尔比为1:1.5~2,所述化合物IV与碱的摩尔比为1:1.1~1.3,所述化合物IV与溶剂B的质量比为1:5~8;
所述控制温度为20~30℃,保温搅拌的时间为5~10h。
7.根据权利要求1所述的5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法,其特征在于:所述步骤(2)中碱为叔丁醇钾、叔丁醇钠、钠氢中的任一种,溶剂B为四氢呋喃、乙腈、DMF中的任一种。
8.根据权利要求1所述的5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法,其特征在于:所述步骤(3)中,所述化合物VII与步骤(2)中化合物IV的摩尔比为0.9~1:1,所述缚酸剂与步骤(2)中化合物IV的摩尔比为1.1~1.3:1,所述溶剂C与步骤(2)中化合物IV的质量比为3~5:1;
所述控制温度为0~10℃,保温搅拌的时间为1~5h。
9.根据权利要求1所述的5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法,其特征在于:所述步骤(3)中缚酸剂为三乙胺、N,N-二异丙基乙胺、DBU、吡啶中的任一种,溶剂C为甲苯、氯苯、二甲苯中的任一种。
10.根据权利要求1所述的5-(2,4,6-三甲苯基)-2-丙酰基-3-羟基-2-环己烯-1-酮的合成方法,其特征在于:所述步骤(4)中,所述催化剂DMAP与步骤(2)中化合物IV的摩尔比为0.05~0.1:1;
所述加入催化剂后控制温度为90~100℃,保温搅拌的时间为1~5h。
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