Three different continuous flow strategies for the generation of important 4-aryl-2-butanone derivatives including the anti-inflammatory drug nabumetone [4-(6-methoxy-2-naphthalenyl)-2-butanone] and the aroma compounds raspberry ketone [4-(4-hydroxyphenyl)-2-butanone] and its methyl ether [4-(4-methoxyphenyl)-2-butanone] were evaluated. All three protocols involve the initial preparation of the corresponding 4-aryl-3-buten-2-ones via Mizoroki–Heck, Wittig, or aldol strategies, which is then followed by selective hydrogenation of the C═C double bond to the desired 4-aryl-2-butanones. The synthetic routes to 4-aryl-3-buten-2-ones were first optimized/intensified on small scale to reaction times of 1–10 min using batch microwave heating technology and then translated to a scalable continuous flow process employing commercially available stainless steel capillary tube reactors. For the synthesis of 4-(4-methoxyphenyl)-3-buten-2-one a further scale-up using a custom-built mesofluidic mini-plant flow system capable of processing several liters per hour was designed to further expand the scale of the process. The final hydrogenation step was performed using a fixed-bed continuous flow hydrogenator employing Ra/Ni as a catalyst.

中文翻译：

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萘丁美酮和相关的4-芳基-2-丁酮的可扩展的两步连续流合成

产生重要的4-芳基-2-丁酮衍生物的三种不同的连续流动策略，包括消炎药萘丁美酮[4-（6-甲氧基-2-萘基）-2-丁酮]和芳香化合物覆盆子酮[4]对-（4-羟基苯基）-2-丁酮]及其甲基醚[4-（4-甲氧基苯基）-2-丁酮]进行了评价。所有这三个方案都涉及通过Mizoroki-Heck，Wittig或aldol策略初始制备相应的4-芳基-3-丁烯-2-酮，然后将C═C双键选择性加氢成所需的4 -芳基-2-丁酮。首先使用间歇微波加热技术将4-芳基-3-丁烯-2-酮的合成路线进行小规模优化/强化，以达到1-10分钟的反应时间，然后转化为使用市售不锈钢的可扩展连续流工艺毛细管反应器。为了合成4-（4-甲氧基苯基）-3-丁烯-2-酮，设计了使用定制的中速微型工厂流系统进行进一步放大处理，该系统每小时可处理数升水，以进一步扩大处理规模。过程。使用采用Ra / Ni作为催化剂的固定床连续流氢化器进行最终的氢化步骤。为了合成4-（4-甲氧基苯基）-3-丁烯-2-酮，设计了使用定制的中速微型工厂流系统进行进一步放大处理，该系统每小时可处理数升水，以进一步扩大处理规模。过程。使用采用Ra / Ni作为催化剂的固定床连续流氢化器进行最终的氢化步骤。为了合成4-（4-甲氧基苯基）-3-丁烯-2-酮，设计了使用定制的中速微型工厂流系统进行进一步放大处理，该系统每小时可处理数升水，以进一步扩大处理规模。过程。使用采用Ra / Ni作为催化剂的固定床连续流氢化器进行最终的氢化步骤。