三百八十八章 旋光问题(1 / 1)

“没事,没事,三碘异酞酰氯可以外购的,可以临时放一放,还有一个侧链是乙酰氧基丙酰氯也很要紧,要不,你们课题组先把这完成了,等着赵定岳把中控方法建立好了,你们又有了思路后再做。”见毛工沮丧的样子,吴总连忙安慰道。

王涛锦组的碘帕醇小试又取得了进展,原来的合成中,DMAC是通过水夹带来去除的,现在,经过改进,可以在乙酸乙酯为溶剂的条件下进行反应,这么一来,树脂吸附的牢固性加深,不用喷干二次,一次性收率又有了一定幅度的提高,如侧链价格下来,成本可以达到与碘海醇同样的水平档了,当然,具体的成本还得中试后才能得知。

丝氨醇已由合作伙伴的厂家试生产成功,如誓太灵要进行中试,随时可以供货,这侧面上对毛工的技术二部也造成了压力,同样是四步反应,一个毕业才一年的大学生搞成了,二十多年工龄的老研究员搞不成,脸面往哪里放?

资料报道的L-乙酰氧基丙酰氯合成路线是由乳酸与冰醋酸在硫酸催化下,用苯带出反应生成的水,先把羟基进行乙酰化保护,再与氯化亚砜反应生成成品,整个过程只有两步,吴总给了毛公一个月的时间,要求拿出合格的成品。

一个星期后,王近之问了问实验员潘满建他们的进展,得知他们已制备得到L-乙酰氧基丙酸,可是,纯度只有百分之七十一,中间体沸点很高,无法蒸馏提纯。

很明显,是乳酸产生自聚,生成了可观数量的双聚及少量的多聚体,如用这两种原料进行反应,唯有先把乳酸减聚,同时大幅度地提高冰醋酸的配比才能减少这个副反应。在制备乳酸左氧时,王近之在这上面吃尽了苦头,周未的联合分析会上,王近之提出了这个建议。

“原来如此,我只想到加大冰醋酸的比例,没想到采购的乳酸自身的自聚。”毛公恍然大悟。

一个星期后,毛公把二百多克L-乙酰氧基丙酰氯样品交给王近之说:“赵定岳给打过气相了,纯度达到99%,质量应当能达标了,你给小试验证一下试试,与外购的有什么不同?”语气中信心满满的。

两天后,验证性的反应液结果出来了,与外购的相比,反应液中的乙酰基杂质多出了百分之零点三。别小看这个杂质,在后处理中是很难精制的,高出这么多,就代表着得多精制一次,损失收率十多个百分点,本来的利润就不高,这么一来,就没有产业化的生产价值了。毛公又一次陷入困境,气相指标更好,为什么验证结果更差呢?

“产品中氯化亚砜没蒸干净,易与分解的乙酸反应生成乙酰氯,再进攻苯环氨基,生成乙酰基。”王涛锦在分析会上站起来给出了结论。

被一个毛头小伙子指出自个的错误,毛工脸上有些挂不住了。不过,事后一想,事实确是如些,只能按照王涛锦的要求重新蒸馏了一次。再次小试跟踪,中间体分析合格,一路地做到了成品,送样到赵定岳的分析室进行全分析。

第三天,赵定岳拿出报告单说:“两个样品的液相纯度与其它指标都合格,,但是,有一个样品的比旋度指标不对,距合格指标低了很多,经过查核,是技术二部合成的乙酰氧基丙酰氯往下制备得到的碘帕醇。”

比旋度不合格,不会搞错吧,酰氯的旋光性主要是由釆购的乳酸决定的,而乳酸是生化制备的,只有左旋体,难道我的运气这么差,用的是合成乳酸?毛工一万个的不信,现场看着赵定岳把样品配好放到旋光光度计里。

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