This blog is written by Liam Almekinder, using only human intelligence. All views are Liam's only, and represents his scientific perspectives as a graduate student in organic chemistry. This page hopes to discuss developments within his own research (even if they occur rarely), organic chemistry as a whole, and life as graduate student. I hope to post monthly, so continue to check back and stop by my weird corner of the internet.
Melting points are one of my favorite scientific techniques in the organic chemistry lab. Often when students are just learning organic chemistry in the lab, melting point is extensively discussed. Only in thermodynamics is the true intricacy revealed about how much melting points can tell us. Melting points (and the underlying physics) appear in a wide variety of applications, including colligative properties, geologic morphologies, and entropic processes.
Firstly to actual melting points in the laboratory. Melting point has yet to be dethroned as the fastest (and cheapest) way to quickly identify and determine the purity of an unknown compound. Organic chemists of the past relied on melting point frequently to determine if their isolations were pure or if further recrystalizaiton is necessary. My favorite examples of this are from old organic chemistry papers that were obviously written by typewriter, with stamped figures and mailed into the editor. These scientists were always meticulous about their melting points, since it was one of the best ways to prove purity. J. Chem. Soc., 1951, 1716-1722, is a paper near and dear to my heart that references melting points multiple times as a way to prove recrystallization issues and impurities, which highlights the power of melting points in the synthetic chemistry lab.
I personally have found great success in labs using melting points and comparing to literature values to assign purity. Melting point is powerful since it can detect impurities that are not seen by a variety of similar analytical techniques. Chromatography, NMR, MS, all require extensive sample preparation and analysis, and this can ignore impurities that may not be seen via chemical techniques. The presence of salts, degradation products, or assorted solvent residues may not always appear in a single analytical technique, but melting point relies on a far more sensitive property to identify impurities: entropy.
Entropy enters our conversation about melting points due to the mixing of subtances and the Clausius clayperon relationship. Molecules in a solid form a network structure of a set volume (and density) and when this volume changes, the structure and entropy change with it. Changing volumes as pressure changes requires a change in the structure of a solid, and therefore a change in the entropy. An easy way to think about it is if you took a building, and tried to change the volume. If you crushed your house, the parts of your house would move in a way that changed the order/entropy in order to fit the new volume. This is seen all the time with the molecular networks that make up rocks and minerals, which face constant heat and pressure under Earth’s surface. Many minerals have similar compositions chemically, but form different crystal networks due to the heat and pressure that forced the molecules to adopt a new structure. Mixing is a similar phenomenon, where entropy is maximized by the random distribution of objects within a larger group. You will never mix things together and find the contents to be perfectly organized. Melting points combine both these concepts into a single phenomenon. Adding heat to a solid network of molecules forces them to adopt a new, more disordered conformation, or in this case a new phase of matter entirely as a liquid. Adding impurities disrupts the molecular network, which decreases the order and makes it even more favorable to melt into a mixed liquid. There is a lot more to say about this overall, so I included some links below that might make for fun reading.
I find the intersection of thermodynamics and melting points to be a really interesting note in experimental chemistry. Often when we are in the lab, we forget how complicated simple phenomena can be when we look at what is going on at the molecular level. My only advice on what to do from here is to take more melting points!
Free energy, entropy and phase changes
Mixtures, entropy, and melting points
Hyperconjugation is my new favorite way to look at molecules. While I had encountered it in the past, I had never truly considered the wider applications to chemical reactivity and conformational analysis until recently in my physical organic and inorganic chemistry lectures. All of a sudden, I am now in possession of a set of X-ray goggles that allow me to see molecules to their very bones. These bones (probabilistic lobes of electron density) show how the molecule has been put together and how it prefers to be in space. Our own skeletons move around constantly, but often prefer to be in a specific conformation based on how our ligaments and muscles connect us. Molecules do the exact same thing, but instead use orbitals and hyperconjugation to arrange themselves. Understanding molecular structure is a really important tool, since structure is the key to reactivity (which makes the chemical world go round).
For every bonding orbital that builds a molecule, there is an antibonding orbital for that bond formed. These bonding and antibonding pairs exist simultaneously for every bond, but electrons preferentially fill up bonding orbitals before moving to higher energy antibonding ones. Hyperconjugation arises when molecular geometry conveniently aligns an electron rich orbital with the antibonding orbital of an electron poor bond. Donating electron density into an antibonding orbital isn’t perfect since it weakens both the donating and accepting bond, but the overall molecule is stabilized. This stabilization works by donating electron density to a reactive center, which lowers the energy and makes the molecule more stable. Thermodynamics, as always, is impartial to what we think is possible as long as the resulting energy is lower.
Confirmational analysis and reactivity provide a unique space for hyperconjugation to be informative for organic compounds. Aligning strong electron donating orbitals with strong electron accepting orbitals proves to be a simple way to predict reactivity and structure. At the same time, secondary orbital interactions could be present in a wide array of structures beyond carbon based molecules. Often in inorganic chemistry, ligand and outlying atoms are able to have secondary interactions with the metal center that strengthen and engage the bonds present. I would be really curious to know if inorganic chemists consider these secondary orbital interactions as hyperconjugation the same way organic chemists do. Since inorganic chemistry relies on deriving and determining molecular orbital diagrams, secondary orbital interactions have already been accounted for by symmetry since every bonding and antibonding orbital have been derived directly. Inorganic chemists may have simply ignored the idea of hyperconjugation (as a term) while deriving molecular orbitals for every possible interaction. Organic chemistry molecular orbitals are more of an artefact of more complex physical chemistry that we do not want to talk about but need to acknowledge. Reactivity pathways are defined in organic chemistry based on trends and absolute energy differences, which use hyperconjugation more as a justification method for reactivity rather than a derived orbital interaction.
Regardless of how hyperconjugation actually works, every chemist should appreciate when mother nature gives us a predictive tool. Predicting and understanding chemical behavior is a tricky and complicated mess, so any hints and clues are essential. It’s easy to apply trends and reactivity to new examples, and that makes any chemical reaction easier to understand. In synthesis, methods development, or any application of organic chemistry, predictions are a powerful tool to guide molecular reactivity and keep moving chemistry forward.
Science is an oddly social enterprise. Often science is presented as a solitary affair, with mad scientists constantly plotting away alone in their lairs, but reality never matches this presentation. Modern science has giant teams, with subgroups and offices bustling with people in and out. The thing most scientists do during their workday is to chat and gossip, either about work, people, or entirely unrelated things (though scientists will never admit this is true). This social sphere makes every lab different and unique, even without considering the actual science going on. Labs never seem like social spaces, but in reality lab work is very social and team focused which creates an interesting workplace dynamic.
I am now at the stage in my adventure where I begin to rotate between labs to find my new research home. This debate is super important as I consider which launchpad I want to use for the rest of my career. It is quite an exciting time as a grad student since I get the joy of learning about lots of chemistry without the crushing expectations and workload to deliver results! Experiencing different lab cultures, meeting new people, and seeing how groups operate is a really interesting social experience. This year, our chemistry department is experimenting with true lab rotations. I recently picked three professors (with a fourth extra one in case I don’t get all three) to rotate through their labs and meet both them and their students. This 3 week period is designed to acclimate me to the lab culture, the work environment, and meet everyone to see if a good scientific relationship can form.
Rotating has been a useful experience so far, for a variety of reasons. Firstly as a glimpse into the lab culture, I get to work closely with older students. They provide a lot of context for what is going on, and provide a glimpse into my own future of what life will look like. The advice I have been given multiple times now is to fully understand a lab, is to ask the students actually doing the work. This helps provide context, since as a rotating student I am not expected to do actual chemistry and work, so being able to see what the expectations are for older students is helpful. Hopefully after 3 weeks of work, and sitting in on group meetings, I can get a good view of the group, and they can get a good view of how I operate too. As I work to find a lab, the rotation process often feels like a game of musical chairs, with only a career at stake.
Despite not knowing what writing lies ahead, embracing the awkwardness of an introduction is a perfect way to start off this page. Like every other blog, this page will be a collection of texts I have written. While I have no way to introduce my future writing, I can provide my reasons for writing and share my hopes for this might become. Posting my random thoughts on the internet hopefully will not be a total waste of my time, but instead be a way to move myself forward as both a writer and a scientist.
My upcoming scientific journey is a major driving reason behind wanting to write and document my experiences on the internet. I am beginning a Ph.D. in organic chemistry, which in my mind, is the start of a grand adventure. As a graduate student, it is my responsibility to not only become an expert in a niche subfield of science but to establish myself within the field as a whole. This webpage will serve as both my networking tool, and my platform for sharing my thoughts and observations about what is going on around me. Scientists cannot operate in a vacuum (though often our experiments do), and I find it my responsibility to constantly read and think about the world around me to inform where research should go. The best way, in my opinion, to do this is by forcing myself to put my own thoughts out into the world. Holding myself to actually publishing a piece of writing forces me to consider, rethink, write, and edit a lot more than I would without a project. Reading other blogs helped me develop this desire to write since this style of writing is easy to engage with. I find Derrick Lowe’s “In the Pipeline” blog through Science really inspiring, since he constantly comments and gives insights into the world of pharmaceuticals and medicinal chemistry. I hope writing my own reflections about the world of chemistry I am entering will expand my own views and understanding.
While I work to expand my horizons as a scientist, I also am obligated to write an entire thesis on some minutiae of observations in organic chemistry. A PhD thesis will not be fun or easy, but writing this blog at the same time will hopefully develop complementary skills to improve my writing. In my experiences reading both scientific and non-scientific writing, writers often struggle with science, and scientists often struggle with writing. To try and overcome this issue, I intend on using this page to become a better communicator both as a technical and non technical writer. There is no better way to become a better writer without simply writing more.
Blogs are really personal endevours, ones that can range from excellent, to absolutely terrible. I hope that at some point during this journey I can publish a piece of writing that is worth reading, and that provokes thought in someone else. With writing and reflection in mind, I look forward to beginning this journey of blogging and advanced scientific study.