When I saw this publication entitled “Polythiophene Compound and Conductive Material Composition,” I was reminded of my brief postdoctoral research in conducting polymers (40 years ago!) with Nobel Prize winner Prof. Alan MacDiarmid at the University of Pennsylvania.
One of the thiophene compounds prepared in the publication is shown in the diagram.
Obviously, in order to achieve selectivity of attack at only one bromide end of the 1,4-dibromobutane, the alkylating agent had to be in high excess.
I am guessing that 30% NaOH was used because 50% NaOH would likely have caused significant dehydrobromination, so the concentration had to be reduced to increase hydration and reduce basicity. At the same time, the NaOH concentration had to be high enough to deprotonate the alcohol and activate the resulting alkoxide for nucleophilic attack (too much water of hydration reduces alkoxide reactivity). If the inventors might have had to keep the aqueous NaOH concentration at that level, that might explain why they use such a huge excess of NaOH, since when adding aqueous NaOH dropwise, the water generated from deprotonation could in theory reduce the NaOH concentration toward the beginning of the reaction.
The reaction was performed at room temperature which additionally minimized dehydrobromination. Reactivity was very good with very high yield at r.t. and 2.5 hours reaction time. I am guessing that the choice of 30% NaOH, instead of higher or lower concentration, was the key process parameter that likely enabled the inventors to dial in the combination of mild temperature and short reaction time to optimize yield and selectivity (avoiding side reactions such as dehydrobromination).
The yield was obviously high, so it is not clear why the inventors used such a very high catalyst loading (53 mole%). Many time chemists will use such high levels of catalyst to ensure good results because they are not focusing on efficiency, they just want high yield. They did have high yield.
I am not sure why the inventors chose THF. That would not have been my first choice, especially knowing that the workup started by adding water, ethyl acetate and hexane just to get two phases that would be easy to separate. I would have chosen a water-immiscible solvent from the outset.
In the end, the results were very good but the process would need to be greatly optimized to reduce the cost if the process ever would go to scale up.
