本文主要研究内容
作者张昆（2019）在《双氯芬酸钠合成工艺研究》一文中研究指出：双氯芬酸钠是一种非甾体类抗炎镇痛药,和其他非甾体类抗炎药物相比具有较强的抗炎作用和较高的安全性。本文结合绿色、安全、经济的工业化生产要求,对目前已有的双氯芬酸钠合成路线进行对比分析,确定较适合工业生产的苯胺法开展了实验研究,为实现双氯芬酸钠工业化生产提供理论依据。首先,对合成中间体二氯二苯胺的溶剂进行了筛选和合成工艺条件的优化研究。分别选用甲苯、二甲苯混合液、正丁醇、环己烷、石油醚、N,N-二甲基甲酰胺等为溶剂,以二氯二苯胺产率为考察指标,比较了几种溶剂的作用效果,确定了较优的溶剂和工艺条件。其次,对二氯二苯胺酰化反应之后的醇解剂进行了筛选实验。分别以甲醇、乙醇、正丙醇、异丙醇、正丁醇为醇解剂,以酰化目标产物N-(2,6-二氯苯基)-苯基-氯乙酰胺产率为考察指标,确定了较优的醇解剂。最后,对中间产物1-(2,6-二氯苯基)-2-吲哚酮和最终的目标产物双氯芬酸钠的合成过程工艺条件进行优化。主要是在单因素试验的基础上,采用响应面法进行优化实验方案的设计,以目标产物的产率为考察指标,优化合成工艺条件。实验合成的目标产物采用红外光谱仪和核磁共振波谱仪进行定性分析,采用紫外分光光度仪和气相色谱仪进行定量分析。合成中间体二氯二苯胺的溶剂为二甲苯混合液,最优合成工艺条件为:反应时间为24小时,催化剂与苯胺质量投料比为0.18,原料2,6-二氯苯酚与苯胺摩尔比为1.20,以苯胺为基准的二氯二苯胺产率为90.05%。中间产物1-(2,6-二氯苯基)-2-吲哚酮的最优合成工艺条件为反应时间2小时,反应温度为140℃,催化剂与N-(2,6-二氯苯基)-苯基-氯乙酰胺质量比为1.20,产物一步产率为97.24%。响应面法分析结果表明:反应温度对产物的产率的效应极显著,反应时间和催化剂用量的线性效应显著,但三者之间的交互作用对产率的效应不显著,而反应温度和反应时间的二次效应极显著。校正模型的相关系数为0.9646,决定系数为0.9191,说明选用的数学模型与实际情况拟合程度较好,能较好反映出因素变量与实验指标之间的相关关系。在因素水平设计范围内,因素对产物产率的影响由大到小依次为反应温度、反应时间、催化剂用量。目标产物双氯芬酸钠合成的最优条件为反应时间为8小时,碱液浓度为0.18g/ml,得到双氯芬酸钠一步产率为87.15%。响应面法分析结果表明:反应时间对产物产率的效应极显著,碱液浓度对产物产率的效应显著,但二者的交互作用效应不显著,而二次效应显著。校正模型的相关系数为0.9285,决定系数为0.8774,说明选用的数学模型与实际情况拟合程度比较好,能较好地反映出因素变量与试验指标之间相关关系。在因素水平设计范围内,因素对产物产率的影响由大到小依次为反应时间、碱液浓度。在上述优化的实验条件做验证性实验,以苯胺为计算基准,双氯芬酸钠的最终产率为63.88%,产品含双氯芬酸钠不低于98.51%,达到了2015年版《中国药典》要求,证实了本研究结果的可行性和可靠性。
Abstract
shuang lv fen suan na shi yi chong fei zai ti lei kang yan zhen tong yao ,he ji ta fei zai ti lei kang yan yao wu xiang bi ju you jiao jiang de kang yan zuo yong he jiao gao de an quan xing 。ben wen jie ge lu se 、an quan 、jing ji de gong ye hua sheng chan yao qiu ,dui mu qian yi you de shuang lv fen suan na ge cheng lu xian jin hang dui bi fen xi ,que ding jiao kuo ge gong ye sheng chan de ben an fa kai zhan le shi yan yan jiu ,wei shi xian shuang lv fen suan na gong ye hua sheng chan di gong li lun yi ju 。shou xian ,dui ge cheng zhong jian ti er lv er ben an de rong ji jin hang le shai shua he ge cheng gong yi tiao jian de you hua yan jiu 。fen bie shua yong jia ben 、er jia ben hun ge ye 、zheng ding chun 、huan ji wan 、dan you mi 、N,N-er jia ji jia xian an deng wei rong ji ,yi er lv er ben an chan lv wei kao cha zhi biao ,bi jiao le ji chong rong ji de zuo yong xiao guo ,que ding le jiao you de rong ji he gong yi tiao jian 。ji ci ,dui er lv er ben an xian hua fan ying zhi hou de chun jie ji jin hang le shai shua shi yan 。fen bie yi jia chun 、yi chun 、zheng bing chun 、yi bing chun 、zheng ding chun wei chun jie ji ,yi xian hua mu biao chan wu N-(2,6-er lv ben ji )-ben ji -lv yi xian an chan lv wei kao cha zhi biao ,que ding le jiao you de chun jie ji 。zui hou ,dui zhong jian chan wu 1-(2,6-er lv ben ji )-2-yin duo tong he zui zhong de mu biao chan wu shuang lv fen suan na de ge cheng guo cheng gong yi tiao jian jin hang you hua 。zhu yao shi zai chan yin su shi yan de ji chu shang ,cai yong xiang ying mian fa jin hang you hua shi yan fang an de she ji ,yi mu biao chan wu de chan lv wei kao cha zhi biao ,you hua ge cheng gong yi tiao jian 。shi yan ge cheng de mu biao chan wu cai yong gong wai guang pu yi he he ci gong zhen bo pu yi jin hang ding xing fen xi ,cai yong zi wai fen guang guang du yi he qi xiang se pu yi jin hang ding liang fen xi 。ge cheng zhong jian ti er lv er ben an de rong ji wei er jia ben hun ge ye ,zui you ge cheng gong yi tiao jian wei :fan ying shi jian wei 24xiao shi ,cui hua ji yu ben an zhi liang tou liao bi wei 0.18,yuan liao 2,6-er lv ben fen yu ben an ma er bi wei 1.20,yi ben an wei ji zhun de er lv er ben an chan lv wei 90.05%。zhong jian chan wu 1-(2,6-er lv ben ji )-2-yin duo tong de zui you ge cheng gong yi tiao jian wei fan ying shi jian 2xiao shi ,fan ying wen du wei 140℃,cui hua ji yu N-(2,6-er lv ben ji )-ben ji -lv yi xian an zhi liang bi wei 1.20,chan wu yi bu chan lv wei 97.24%。xiang ying mian fa fen xi jie guo biao ming :fan ying wen du dui chan wu de chan lv de xiao ying ji xian zhe ,fan ying shi jian he cui hua ji yong liang de xian xing xiao ying xian zhe ,dan san zhe zhi jian de jiao hu zuo yong dui chan lv de xiao ying bu xian zhe ,er fan ying wen du he fan ying shi jian de er ci xiao ying ji xian zhe 。jiao zheng mo xing de xiang guan ji shu wei 0.9646,jue ding ji shu wei 0.9191,shui ming shua yong de shu xue mo xing yu shi ji qing kuang ni ge cheng du jiao hao ,neng jiao hao fan ying chu yin su bian liang yu shi yan zhi biao zhi jian de xiang guan guan ji 。zai yin su shui ping she ji fan wei nei ,yin su dui chan wu chan lv de ying xiang you da dao xiao yi ci wei fan ying wen du 、fan ying shi jian 、cui hua ji yong liang 。mu biao chan wu shuang lv fen suan na ge cheng de zui you tiao jian wei fan ying shi jian wei 8xiao shi ,jian ye nong du wei 0.18g/ml,de dao shuang lv fen suan na yi bu chan lv wei 87.15%。xiang ying mian fa fen xi jie guo biao ming :fan ying shi jian dui chan wu chan lv de xiao ying ji xian zhe ,jian ye nong du dui chan wu chan lv de xiao ying xian zhe ,dan er zhe de jiao hu zuo yong xiao ying bu xian zhe ,er er ci xiao ying xian zhe 。jiao zheng mo xing de xiang guan ji shu wei 0.9285,jue ding ji shu wei 0.8774,shui ming shua yong de shu xue mo xing yu shi ji qing kuang ni ge cheng du bi jiao hao ,neng jiao hao de fan ying chu yin su bian liang yu shi yan zhi biao zhi jian xiang guan guan ji 。zai yin su shui ping she ji fan wei nei ,yin su dui chan wu chan lv de ying xiang you da dao xiao yi ci wei fan ying shi jian 、jian ye nong du 。zai shang shu you hua de shi yan tiao jian zuo yan zheng xing shi yan ,yi ben an wei ji suan ji zhun ,shuang lv fen suan na de zui zhong chan lv wei 63.88%,chan pin han shuang lv fen suan na bu di yu 98.51%,da dao le 2015nian ban 《zhong guo yao dian 》yao qiu ,zheng shi le ben yan jiu jie guo de ke hang xing he ke kao xing 。
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论文作者分别是来自吉林化工学院的张昆，发表于刊物吉林化工学院2019-07-12论文，是一篇关于双氯芬酸钠论文,合成论文,工艺优化论文,响应面法论文,吉林化工学院2019-07-12论文的文章。本文可供学术参考使用，各位学者可以免费参考阅读下载，文章观点不代表本站观点，资料来自吉林化工学院2019-07-12论文网站，若本站收录的文献无意侵犯了您的著作版权，请联系我们删除。
标签：双氯芬酸钠论文; 合成论文; 工艺优化论文; 响应面法论文; 吉林化工学院2019-07-12论文;