Chem 634 Advanced Organic Chemistry Synthesis and Reactivity Prof Joseph Fox Chemical Database Searching Handout 5 Handout 5 Introduction to Reaction searching for functional group tolerance on Beilstein commander In this tutorial we will demonstate how to use Beilstein to search for functional group tolerance For this specific search we will use the example of cleaving a methyl ester preferentially in the presence of a Fmoc protected amine The type of reaction that we are interested in is shown below H N MeO2C R H N HOOC O R O As an example we will say that we are interested in precedents for removing the ester in the presence of Fmoc under basic conditions This is not trivial since both groups are cleaved by base we are going to see if it can be done selectively Note that we are not going to limit our search to alpha amino acids Rather we will begin by searching broadly As long as we get less than 500 hits for the reaction search it will be easy to scan for desirable precedents in a short 30 min amount of time Draw the four structures below and identify them as reactants and products in the Reaction Editor Be sure to put the free sites in as shown Note what we are doing here we are specifying that both the product and the starting material have an Fmoc protected amine We are then specifying that the starting material contains a methyl ester and the product contains an acid Begin the search This search should bring up at least 139 hits The first thing that you will notice is that reactions 1 through 4 have nothing to do with the reaction we want That s OK our idea was to conduct a very open ended search we are willing to sort through these examples in order to find ones we want Scroll through and find some useful precendents For example if we go forward to Hit 20 we find a precedent of exactly what we are looking for At low temperature LiOH will selectively remove the methyl ester without touching the Fmoc Scroll through and find additional precedents for removing the ester in the presence of the Fmoc under basic conditions
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