Chem 634, Advanced Organic Chemistry- Synthesis and ReactivityProf. Joseph FoxChemical Database Searching- Handout 5 Handout 5: Introduction to Reaction searching for functional group tolerance on Beilstein commanderMeO2CHNR OHOOCHNR OIn 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 thepresence of a Fmoc protected amine. The type of reaction that we are interested in is shownbelow.As an example, we will say that we are interested in precedents for removing the ester in thepresence of Fmoc under basic conditions. This is not trivial, since both groups are cleaved bybase-- 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 bysearching broadly. As long as we get less than 500 hits for the reaction search, it will be easy toscan 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 ReactionEditor. Be sure to put the free sites in as shown. Note what we are doing here: we are specifyingthat both the product and the starting material have an Fmoc protected amine. We are thenspecifying that the starting material contains a methyl ester, and the product contains an acid.Begin the searchThis search should bring up at least 139 hits. The first thing that you will notice is that reactions 1through 4 have nothing to do with the reaction we want. That’s OK, our idea was to conduct avery open ended search-- we are willing to sort through these examples in order to find ones wewant. 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 Fmocunder basic
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