CN104177307B - 一种制备2-取代-4-甲基-3-噻唑啉类化合物的方法 - Google Patents
一种制备2-取代-4-甲基-3-噻唑啉类化合物的方法 Download PDFInfo
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Abstract
本发明提供了一种2‑取代‑4‑甲基‑3‑噻唑啉类化合物的制备方法,其特征是用无水乙醇或水作溶剂,采用食用香料2,5‑二甲基‑2,5‑二羟基‑1,4‑二噻烷、醛类食用香料和食品工业用加工助剂氨水为原料,在5~45℃下反应20~90min,就可以得到2‑取代基‑4‑甲基‑3‑噻唑啉;其中2,5‑二甲基‑2,5‑二羟基‑1,4‑二噻烷与醛的摩尔比为1∶2~1∶3,醛与氨水的摩尔比为1∶1~1∶2。反应结束后进行后处理,除去低沸点物质,减压蒸馏,就可以得到2‑取代‑4‑甲基‑3‑噻唑啉类化合物。该方法所用原料安全、易得、操作简单、易于工业化。
Description
技术领域
本发明涉及一种制备2-取代-4-甲基-3-噻唑啉类化合物的方法。2-取代-4-甲基-3-噻唑啉类化合物是一类香料化合物,近年来随着分析技术的发展,越来越多的2-取代-4-甲基-3-噻唑啉类化合物在食品的挥发性成分中被检测出来,特别是2-烷基-4-甲基-3-噻唑啉类化合物,它们主要天然存在于烤牛肉、烤芝麻等食物中,具有桃子、浆果、巧克力、大蒜等香气;其中,4-甲基-3-噻唑啉、2-乙基-4-甲基-3-噻唑啉和2-异丙基-4-甲基-3-噻唑啉已通过安全评价,被美国食用香料与萃取物制造者协会(FEMA)列入一般公认安全(GRAS)的食用香料名单中,可用于调配食用香精,用于食品的加香。
背景技术
关于2-取代-4-甲基-3-噻唑啉的合成方法中,目前文献报道的是以1-巯基-2-丙酮、醛或酮类化合物和氨水(或者氨气)为原料,通过缩合环化反应,得到2-取代-4-甲基-3-噻唑啉。
反应式如下:
该方法存在的主要问题是:(1)所需的原料1-巯基-2-丙酮不易获得,需要采用氯丙酮或溴丙酮制得,而氯丙酮或溴丙酮有很高的毒性和强烈的催泪性;(2)采用1-巯基-2-丙酮制备2-取代-4-甲基-3-噻唑啉时为了简化工艺,1-巯基-2-丙酮不经分离直接反应,终产物中会含有微量的氯丙酮或溴丙酮;(3)1-巯基-2-丙酮在常温下非常不稳定,易被氧化成二硫醚,难以长时间保存。
本发明的目的是采用一种易得、稳定和安全的原料,提供一种新的制备2-取代-4-甲基-3-噻唑啉类化合物的通用方法,以解决现有合成方法中存在的问题。
发明内容
本发明所要解决的技术问题是提供一种原料易得、稳定、安全,操作方便的制备2-取代-4-甲基-3-噻唑啉类化合物的方法。
本发明涉及2-取代-4-甲基-3-噻唑啉类化合物的制备方法,其特征是采用国内外已经批准允许使用的食用香料2,5-二甲基-2,5-二羟基-1,4-二噻烷、醛类食用香料和食品工业用加工助剂氨水为原料,用无水乙醇或水为溶剂,在5~45℃下反应20~90min,就可以得到2-取代基-4-甲基-3-噻唑啉;其中优选反应温度是10~30℃,优选反应时间是30~60min,反应中所用的氨水可以用氨气代替。
反应式如下:
注:R-代表氢、甲基、乙基、正丙基、异丙基、正丁基、呋喃基。
本发明制备方法的主要过程是:
向装有球形冷凝管的四口瓶中加入2,5-二甲基-2,5-二羟基-1,4-二噻烷、醛和溶剂,在磁力搅拌下,在5~45℃下,通过滴液漏斗缓慢滴加氨水(或者通入氨气);滴加完毕后,继续在5~45℃下反应20~90min。反应完毕后,分出有机相,用乙醚萃取水相;合并有机相和乙醚萃取物,用饱和食盐水洗涤,经无水硫酸镁干燥,过滤,旋蒸除去乙醚,得到2-取代-4-甲基-3-噻唑啉粗品,粗品再经减压蒸馏提纯,得到2-取代-4-甲基-3-噻唑啉。
用本发明方法制备的2-取代-4-甲基-3-噻唑啉类化合物均采用1HNMR、13CNMR和质谱对它们的结构进行了确认。
本发明的制备方法克服了现有制备方法中的缺点,主要优点在于:
1、本发明的合成方法所用原料安全、易得、稳定;
2、操作简单、方便。
本发明涉及的2-取代-4-甲基-3-噻唑啉类化合物的制备方法将通过下面的实施例得到更具体的描述。
具体实施方式
实施例1 4-甲基-3-噻唑啉的制备
室温下,向装有球形冷凝管的四口瓶中加入2,5-二甲基-2,5-二羟基-1,4-二噻烷(0.05mol,9.01g)、37%的甲醛溶液(0.13mol,10.54g)和15ml去离子水,在磁力搅拌下,在5~10℃下通过滴液漏斗缓慢滴加25%的氨水(0.14mol,9.52g),加完后在这个温度下继续反应20min。反应完毕后,分出有机相,水相用乙醚萃取(20ml×2),合并有机相,用饱和食盐水洗涤(15ml×3)有机相,经无水硫酸镁干燥,过滤,旋蒸除去乙醚,得到4-甲基-3-噻唑啉的粗品。采用气相色谱分析其含量,经计算4-甲基-3-噻唑啉的产率大于52%;粗品经减压蒸馏,收集18-20℃/3mbar的馏分得到无色液体,含量大于98%。
实施例2 2,4-二甲基-3-噻唑啉的制备
向装有球形冷凝管的四口瓶中加入2,5-二甲基-2,5-二羟基-1,4-二噻烷(0.05mol,9.01g)、40%的乙醛溶液(0.13mol,14.3g)和15ml无水乙醇,在磁力搅拌下,在10~15℃下通过滴液漏斗缓慢滴加25%的氨水(0.14mol,9.52g),滴加完毕后在此温度下继续反应30min。反应完毕后,分出有机相,水相用乙醚(20ml×2)萃取,合并有机相,用饱和食盐水(15ml×3)洗涤有机相,经无水硫酸镁干燥,过滤,旋蒸除去乙醚,得到2,4-二甲基-3-噻唑啉的粗品。采用气相色谱分析其含量,经计算2,4-二甲基-3-噻唑啉的产率大于65%;粗品经减压蒸馏,收集18℃/3mbar的馏分得到无色液体,含量大于97%。
实施例3 2-乙基-4-甲基-3-噻唑啉的制备
向装有球形冷凝管的四口瓶中加入2,5-二甲基-2,5-二羟基-1,4-二噻烷(0.05mol,9.01g)、丙醛(0.13mol,7.55g)和15ml去离子水,在磁力搅拌下,在15~20℃下通过滴液漏斗缓慢滴加25%的氨水(0.14mol,9.52g),滴加完毕后在此温度下继续反应60min。反应完毕后,分出有机相,水相用乙醚(20ml×2)萃取,合并有机相,有机相用饱和食盐水(15ml×3)洗涤,经无水硫酸镁干燥,过滤,旋蒸除去乙醚,得到2-乙基-4-甲基-3-噻唑啉的粗品。利用气相色谱分析其含量,经计算2-乙基-4-甲基-3-噻唑啉的产率大于80%;粗品经减压蒸馏,收集30-31℃/3mbar的馏分得到无色液体,含量大于98%。
实施例4 2-丙基-4-甲基-3-噻唑啉的制备
向装有球形冷凝管的四口瓶中加入2,5-二甲基-2,5-二羟基-1,4-二噻烷(0.05mol,9.01g)、丁醛(0.13mol,9.37g)和15ml无水乙醇,在磁力搅拌下,在20~25℃下通过滴液漏斗缓慢滴加25%的氨水(0.14mol,9.52g),滴加完毕后在此温度下继续反应30min。反应完毕后,分出有机相,水相用乙醚(20ml×2)萃取,合并有机相,有机相用饱和食盐水(15ml×3)洗涤,经无水硫酸镁干燥,过滤,旋蒸除去乙醚,得到2-丙基-4-甲基-3-噻唑啉的粗品。利用气相色谱分析其含量,经计算2-丙基-4-甲基-3-噻唑啉的产率为84%;粗品经减压蒸馏,收集39-40℃/2mbar的馏分得到无色液体,含量大于96%。
实施例5 2-异丙基-4-甲基-3-噻唑啉的制备
向装有球形冷凝管的四口瓶中加入2,5-二甲基-2,5-二羟基-1,4-二噻烷(0.05mol,9.01g)、异丁醛(0.13mol,9.36g)和15ml去离子水,在磁力搅拌下,在25~30℃下通过滴液漏斗缓慢滴加25%的氨水(0.14mol,9.52g),滴加完毕后在此温度下继续反应60min。反应完毕后,分出有机相,水相用乙醚(20ml×2)萃取,合并有机相,有机相用饱和食盐水(15ml×3)洗涤,经无水硫酸镁干燥,过滤,旋蒸除去乙醚,得到2-异丙基-4-甲基-3-噻唑啉的粗品。利用气相色谱分析其含量,经计算2-异丙基-4-甲基-3-噻唑啉的产率大于90%;粗品经减压蒸馏,收集51-52℃/6mbar的馏分得到无色液体,含量大于94%。
实施例6 2-丁基-4-甲基-3-噻唑啉的制备
向装有球形冷凝管的四口瓶中加入2,5-二甲基-2,5-二羟基-1,4-二噻烷(0.05mol,9.01g)、戊醛(0.13mol,11.18g)和15ml无水乙醇,在磁力搅拌下,在30~35℃下通过滴液漏斗缓慢滴加25%的氨水(0.14mol,9.52g),滴加完毕后在此温度下继续反应30min。反应完毕后,分出有机相,水相用乙醚(20ml×2)萃取,合并有机相,有机相用饱和食盐水(15ml×3)洗涤,经无水硫酸镁干燥,过滤,旋蒸除去乙醚,得到2-丁基-4-甲基-3-噻唑啉的粗品。粗品利用气相色谱分析其含量,经计算2-丁基-4-甲基-3-噻唑啉的产率为89%。粗品经减压蒸馏,收集51-52℃/3mbar的馏分得到无色液体,含量大于96%。
实施例7 2-呋喃基-4-甲基-3-噻唑啉的制备
向装有球形冷凝管的50ml四口瓶中加入2,5-二甲基-2,5-二羟基-1,4-二噻烷(0.05mol,9.01g)、糠醛(0.13mol,12.49g)和20ml无水乙醇,在磁力搅拌下,40~45℃下通过滴液漏斗缓慢滴加25%的氨水(0.14mol,9.52g),滴加完毕后在此温度下继续反应60min。反应完毕后,分出有机相,水相用乙醚(20ml×2)萃取,合并有机相,用饱和食盐水(15ml×3)洗涤有机相,经无水硫酸镁干燥,过滤,旋蒸除去乙醚,得到2-呋喃基-4-甲基-3-噻唑啉的粗品。利用气相色谱分析其含量,经计算2-呋喃基-4-甲基-3-噻唑啉的产率为53%;粗品经减压蒸馏,收集76-78℃/2mbar的馏分,得到浅黄色透明液体,含量大于92%。
Claims (2)
1.一种香料化合物,其特征在于具有如下结构:
其中,R为呋喃基。
2.根据权利要求1所述化合物的制备方法,其特征在于,以无水乙醇作溶剂,采用食用香料2,5-二甲基-2,5-二羟基-1,4-二噻烷、糠醛和食品工业用加工助剂氨水为原料,反应温度是20~45℃,反应时间是30~90min,2,5-二甲基-2,5-二羟基-1,4-二噻烷与糠醛的摩尔比为1∶2~1∶3,糠醛与氨水的摩尔比为1∶1~1∶2。
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