in the chemical literature: metabolite identification & synthesis

Welcome to Chem Help ASAP. In this video we’ll see how organic chemistry can
be used to solve a practical, real world problem. The work in this video was performed by a
team of scientists led by Dr. Belgin Canturk at Corteva Agriscience in Indianapolis, IN. The work was published in the journal Organic
Process Research & Development. The citation is on the following slides as
well as in the video description. [turn page]
On the screen, to the left, is a molecule, an herbicide called Rinskor active. Before being approved for use on crops, herbicides
must be studied. In studying the fate of Rinskor active in
the environment, the Corteva scientists found that the ester of Rinksor active is hydrolyzed,
the ether is demethylated, and the ring undergoes nitration. Here’s the problem. The Corteva scientists did not know the exact
structure of the nitration product. It could have been either the top (#1) or
bottom (#2) structure. They differ in the position of the nitro group. Furthermore, they needed to know the structure
of the nitrated metabolite to study the molecule and get regulatory approval. To solve this problem, the Corteva scientists
needed to make the metabolite in the laboratory. [turn page]
Making metabolite #1 was relatively easy. Both the benzyl ester and methyl ether of
Rinskor active were cleaved in one step with BBr3. The resulting product could be nitrated with
sodium nitrate and sulfuric acid. We do have a regiochemical issue. Remember that the regiochemistry of EAS reactions
(like the nitration) are controlled by the strongest activing group. For this molecule, the strongest activating
group is the OH. This is an ortho,para-director. The ortho positions are already occupied,
so the nitro group is introduced in the para position. The other possible metabolite (#2) was much
more difficult to synthesize, and we will not go into that chemistry. With both possible isomers of the nitrated
metabolite in hand, what did the Corteva scientists learn? Well, they learned that the top isomer is
the structure of the nitrated metabolite of Rinskor active that forms in the soil. This result allowed the company to continue
safety testing and ultimately gain regulatory approval. In conclusion, the scientists at Corteva needed
to determine conclusively the structure of a molecule, and the only way to determine
the structure confidently required synthesizing the molecule in the laboratory. Their synthesis relied upon a regioselective
aromatic nitration. Synthesis is often the most reliable tool
for determining the structure of an unknown molecule. If you want to see more details about the
breakdown of Rinksor active in the environment, then check out the reference on this slide
or in the video description. Please subscribe, like, or leave a comment. Take care.

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