Part One: A Flow Reactor With In-Line Analytics: Design and Implementation Part Two: In-Line Derivatization of Protic Compounds for GC/MS Reaction Monitoring

The creation of an automated synthetic reaction system with in-line analytics is presented in two parts. First, the design and implementation of a flow reactor system complete with in-line gas chromatography mass spectrometry (GC/MS) analytical instrument is discussed. The testing and validation of the systems components was completed in order to create a fully automated chemical reaction system capable of running, analyzing and optimizing a synthetic transformation without operator intervention with the system. The results of the synthetic transformation of allyl phenyl ether to 2-allyl phenol are presented to demonstrate the systems capabilities.

Secondly, an approach was developed to combine a sample preparation step known as derivatization with the reactor-analysis system. Many compounds are not directly amenable to GC/MS analysis, and derivatization is used as a sample preparation step to chemically functionalize compounds so that they can be analyzed with GC/MS. The use of derivatization in combination with a reactor-GC/MS system was introduced to help increase the scope of reactions that can be run and analyzed using this approach. The design, validation and use of a flow derivatization setup was completed and combined to the flow reactor and analysis system without interrupting the already established sample transfer system. The hydrolysis of benzonitrile with phthalic acid is used as a model reaction to demonstrate the reproducibility of the derivatization setup.