常温常压下稳定,避免与氧化物、水分及强碱接触。
4-氯甲基苯甲酰氯是一种无色液体,化学式为C₈H₆Cl₂O。它是医药、农药、染料和材料等多个领域的关键中间体。近年来,由于其广泛的应用需求逐渐增加,市场对这一物质的需求也随之增长,使得从业者看到了它广阔的发展前景。
制备过程首先将300g的4-甲基苄醇与0.075g的过氧化二苯甲酰投入带有尾气吸收装置的反应器中,开启搅拌并用胶头滴管滴加三乙醇胺约0.12g。密闭反应器后开始升温至55℃,随后打开氯气阀门通入氯气,并将通氯速度设置在400~500ml/min。该过程为放热反应,温度会自动上升,待升至60℃以上时开始保温,保温过程中温度始终保持在60~75℃之间。每隔一小时补加过氧化二苯甲酰0.075g,总计补加三次后停止补加。通过GC气谱跟踪,在保温8小时后,若气谱显示4-羟甲基二氯苄的量≤0.05%则停止通入氯气,反应结束。随后用氮气驱除多余氯气,并降温至室温,所得粗品约571g。
接着将上述体系加热至60℃以上,然后使用200ml恒压滴液漏斗以每5秒一滴的速度逐步加入水,整个过程耗时1小时后暂停。继续通过GC气谱监测,在反应进行19小时后若4-羟甲基三氯苄的量≤0.05%则可判断反应完成,此时所用水量为116g。随后将体系降温至室温并称重,总重量约为659g,根据质量守恒原则,推算出约28g的氯化氢气体被引入尾气吸收装置。
最后向上述体系中加入2636g乙醚和2g DMF催化剂,并控制反应温度在室温。开始以100g/h的速度滴加草酰氯共624g,待滴加完毕后继续反应。通过GC气谱跟踪,在14小时后确认4-氯甲基苯甲酰氯的纯度为96.3%时可判定反应结束。随后进行常压回收乙醚和草酰氯,并用5%液碱中和余下体系,调整pH值至7~8后静置、分层并除去水相。最终通过减压(6mmHg)蒸馏126~128℃的馏分获得产品4-氯甲基苯甲酰氯,收率为88.8%,纯度达到99.4%。
中文名称 | 英文名称 | CAS号 | 化学式 | 分子量 |
---|---|---|---|---|
对甲基苯甲酰氯 | 4-methyl-benzoyl chloride | 874-60-2 | C8H7ClO | 154.596 |
对氯甲基苯甲酸 | p-(chloromethyl)benzoic acid | 1642-81-5 | C8H7ClO2 | 170.595 |
中文名称 | 英文名称 | CAS号 | 化学式 | 分子量 |
---|---|---|---|---|
4-(氯甲基)苯甲酰胺 | 4-(chloromethyl)benzamide | 84545-14-2 | C8H8ClNO | 169.611 |
对氯甲基苯甲酸 | p-(chloromethyl)benzoic acid | 1642-81-5 | C8H7ClO2 | 170.595 |
1-[4-(氯甲基)苯基]乙酮 | 1-(4-(chloromethyl)phenyl)ethan-1-one | 54589-56-9 | C9H9ClO | 168.623 |
4-氯甲基苯甲酸甲酯 | p-methyloxycarbonylbenzyl chloride | 34040-64-7 | C9H9ClO2 | 184.622 |
4-(氯甲基)-N-羟基苯甲酰胺 | α-chloro-N-hydroxy-p-toluamide | 150191-54-1 | C8H8ClNO2 | 185.61 |
4-(氯甲基)-n-甲基苯甲酰胺 | 4-(chloromethyl)-N-methylbenzamide | 220875-88-7 | C9H10ClNO | 183.637 |
The efficacy and side-effects of drugs do not just reflect the biochemical and pharmacodynamic properties of the parent compound, but often comprise of cooperative effects between the properties of the parent and active metabolites. Metabolites of imatinib, nilotinib and midostaurin have been synthesised and evaluated in assays to compare their properties as protein kinase inhibitors with the parent drugs. The N-desmethyl-metabolite of imatinib is substantially less active than imatinib as a BCR-ABL1 kinase inhibitor, thus providing an explanation as to why patients producing high levels of this metabolite show a relatively low response rate in chronic myeloid leukaemia (CML) treatment. The hydroxymethylphenyl and N-oxide metabolites of imatinib and nilotinib are only weakly active as BCR-ABL1 inhibitors and are unlikely to play a role in the efficacy of either drug in CML. The 3-(R)-HO-metabolite of midostaurin shows appreciable accumulation following chronic drug administration and, in addition to mutant forms of FLT3, potently inhibits the PDPK1 and VEGFR2 kinases (IC50 values