布洛芬合成工艺论文[1]

镇痛消炎药布洛芬合成工艺的研究

摘要

布洛芬(ibuprofen)，化学名为2一(4一异丁基苯基)丙酸，为新一代非甾体消炎镇痛药物，具有比阿司匹林更强的解热、消炎和镇痛作用，副作用则比阿司匹林小得多。因此自上世纪70年代末上市以来，以其疗效高, 副作用小为特点而而获得了迅速发展，现已成为生产量和使用量最大的消炎解热镇痛药之一。1987 年, 它在全部解热镇痛消炎药物的23 亿美元销售额中占18%的份额。1993 年上升至30%以上。目前,全世界布洛芬的总产量为8000 吨左右。

布洛芬的合成方法主要包括：(1)转位重排法；(2) 醇羰基化法；(3)烯烃羰基化法；(4) 卤代烃羰基化法；(5) 烯烃加氢法；(6)环氧丙烷重排法等。

本文以对异丁基苯甲醛为原料，分5步来合成布洛芬。考察了反应气氛、温度、催化剂的量、溶剂等反应条件对反应的影响。论文在对K4[Fe(CN)6]性质和苄氯氰化反应特点进行分析的基础之上，引入催化的方式，以无毒K4[Fe(CN)6]作为氰化试剂，实现了苄氯氰化反应中氰化试剂的无毒化，为苄氯向苯乙腈类化合物的转化探索了一种相对绿色的新方法。

温度对反应的影响如下：随着温度的升高，产率也随之升高。但是,当反应温度高于某一反应温度时，产率又有所下降。从动力学角度分析，我们可以知道：随着反应温度的升高，反应活性即反应速率也升高，催化剂的催化效率也升高，反应收到的产率也升高。在某一温度附近达到最优化，之后继续升温使催化剂部分容易失活，并生成了其它副产物，反应的产率也随之下降。因此该反应的最优反应温度是180 ℃。在最优反应温度下，苯乙腈的产率可以达到97.8%。

考察了反应气氛对反应的影响。发现当参与反应的物质的量很少时，在其它条件完全相同的情况下，无论是否有N2保护，产率基本相差不大。但是从工业角度来说，反应物的量很大，可能会有各种情况出现。所以，应以N2

保护为最优条件。

总之，通过一系列的研究发现当在N2保护下，以PMHS为还原剂使对异丁基苯甲醛转变成醇，在SOCl2的作用下对其进行氯化。使用无毒的K4[Fe(CN)6]作为氰化试剂在CuI催化下，于180℃下与苄氯发生反应得到的苄腈化合物水解制取布洛芬，取得了最佳效果。

关键词：布洛芬，对异丁基苯甲醛，碘化亚铜，亚铁氰化钾

THE RESEARCH ON THE SYNTHESIS OF

ANALGESIC ANTI-INFLAMMATORY DRUG

IBUPROFENT

ABSTRACT

Ibuprofen (ibuprofen), a chemical known as 2 (4 a isobutyl phenyl) propionic acid, as a new generation of non-steroidal anti-inflammatory analgesic drugs, with more anti-inflammatory and analgesic effects than aspirin antipyretic.Side effects are much smaller than aspirin. Therefore, since the late 70s of last century on the market, with its high efficacy and fewer side effects for the characteristics of and access to the rapid development, has become one of the largest production and use of

anti-inflammatory anti-inflammatory drugs. In 1987, it is accounted for 18% share in all the 2.3 billion sales for antipyretic analgesic anti-inflammatory drugs. 1993 increased to 30%. Currently, the world's total output of of ibuprofen is about. 8,000 tons.

The synthesis of ibuprofen include: (1) translocation Rearrangement;

(2) alcohol carbonylation; (3) olefin carbonylation; (4) halogenated

hydrocarbons carbonylation; (5) olefin hydrogenation Law; (6) rearrangement of propylene oxide method.

This paper as raw material for iso-benzaldehyde, the synthesis of ibuprofen in 5 steps. The effect of reaction atmosphere, temperature, amount of catalyst, solvent and other reaction conditions on the reaction. Paper in K4 [Fe (CN) 6] reaction the nature and characteristics of benzyl cypermethrin on the basis of the analysis, the introduction of catalytic approach to non-toxic K4 [Fe (CN) 6] as the cyanide reagent to achieve the benzyl Cyanuric chloride reaction in non-toxic cyanide reagent for benzyl chloride to phenyl acetonitrile compounds into the green to explore a relatively new method.

The impact of temperature on the reaction is as follows: as the temperature increases, production rate also increased. However, when the reaction temperature is higher than a certain temperature, the yield have declined. From the dynamic point of view, we can know: With the reaction temperature, the reaction activity of the reaction rate also increased, the catalytic efficiency is increased, the reaction also increased the yield received. Reaches a certain temperature near the optimum, and then continue to heat up some easy deactivation of the catalyst, and other

by-products generated, the reaction yield is lower. Therefore, the optimal reaction temperature is 180 ℃. Under the optimal reaction temperature, the yield of benzene acetonitrile up to 97.8%. .

The effect of reaction atmosphere on the reaction. Found that the reaction of the small amount of substance, in the case of other conditions the same, regardless of whether N2 protection, the basic difference between the yield little. But from the industrial point of view, a large amount of reactants, there may be a variety of situations. So, should be protected for the optimal conditions N2

In short, through a series of studies found that under the protection of the N2 to PMHS as the reducing agent to benzaldehyde on the iso into alcohol,