Synthesis of 1-methoxy-2-indanone

Essay by arakul600College, UndergraduateB, September 2010

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Synthesis of 1-methoxy-2-indanone

Ex. 1

As chief scientific officer of Mark, Inc. R&D, I have the responsibility of reviewing proposed syntheses for new drugs that our company wishes to develop. Our president has identified 1-methoxy-2-indanone as a desired target, and two groups in our R&D department have proposed syntheses for this molecule. After careful evaluation, I have selected the synthesis from Research Group A as the one most likely to achieve success.

Two steps in the proposal from Research Group B have problems that will cause those steps, and hence the overall synthesis, to fail. In step 1, the use of Br2 in the presence of FeBr3 will result in bromination of the aromatic ring to give 5-bromoindane rather than 1-bromoindane. Had Br2 in the presence of ultraviolet light been employed instead, the reaction would likely have succeeded to give the desired 1-bromoindane. Each of the next three steps from group B would give the stated product from the stated reactant, although I do not understand why group B would want to prepare indane-1,2-dione (the stated product from step 4).

Certainly, the final step would not yield 1-methoxy-2-indanone from indane-1,2-dione. Lithium aluminum hydride is a powerful reducing agent, and both ketone groups would be reduced to alcohols to give 1,2-dihydroxyindane as the final product. Furthermore, the protic solvent methanol is likely to react with LiAlH4 as well. All-in-all, step 5 would be a messy reaction.

I respectfully disagree with our president that 1-methoxy-2-indanone is a good candidate for synthesis. Many over-the-counter NSAIDs such as aspirin, ibuprofen, and naproxen contain carboxylic acid groups, and our target molecule does not. I strongly encourage research group A to conduct a thorough literature search prior to investing the time, effort, and material costs needed to synthesize 1-methoxy-2-indanone. In addition, I recommend that this group...