My first two weeks of research have been very eye opening and pretty challenging at times. It’s taken me longer than I expected to adjust to this new way of working and I’ve really struggled with a lack of purpose and ✨imposter syndrome✨. However, now I’ve completed my second week I feel composed and positive, ready to write some overall reflections about what I’ve been learning.
My project is about ring cascade expansion reactions and how to effectively synthesise their starting materials. It’s difficult to make medium sized rings in organic chemistry because of the loss of entropy when forming them, and their synthesis normally requires impractical high dilution conditions.
One way of making them is by using an internal nucleophilic catalyst which can allow the ring to be formed via a smaller cyclic intermediate. This process is promising since medium sized rings are very useful in medicinal chemistry but hard to make as I mentioned before.
Many students undertaking projects in this field of research spend much of their time figuring out how to synthesise linear starting materials which they can then use to carry out ring expansion. This means that sometimes only small periods of time are dedicated to actually making new, commercially useful medium rings.
My first aim was to figure out a general method to make these linear starting materials from different secondary amines and alkyl bromides (building blocks). This will allow time to be used more efficiently in the future, allowing more time to be spent making medium rings. This took up most of the first week and after reading through many research papers I was pretty confident that I’d found the best way to make them.
I dedicated the second week to making some new ‘building blocks’ which are the first set of reagents. (Basically, the synthesis goes building blocks (secondary amines and alkyl bromides) to linear starting materials to medium rings.)
I designed many secondary amine building blocks and used a search tool called Reaxys to figure out the best way of making them in a lab. Of all the ideas I had, we narrowed it down to two molecules which will be made in the lab this week, sadly not by me ☹. It does feel quite satisfying that I designed them though.
Looking forward to this week, I plan on creating a table containing all the building blocks, which MChem students can use to easily synthesis their starting materials and ensure as many new molecules can be made as possible, while preventing repeats.