Pete Tcharkovsky,A Freddy Chopin,A Johnny Strauss,A Eddie Greig, Jimmy Puccini,A Archduke MetallicaA and Günther SchlonkB*
Abstract: Chemists are constantly pushing the boundaries of synthetic methodology. More specifically, they are finding new ways of doing the same reactions they were doing 20 years ago, with a twist. It might be a mechanochemically generated Grignard reagent, an electrochemical Birch reduction, a lithiation in flow, a photocatalytic halogenation or even an organocatalytic Suzuki coupling. Big whoop. However, pointing this out doesn’t change the fact that we have to compete with these people for grants. We defiantly can’t beat them, so we’ve developed our own iteration of this copy-catalysis by exposing chemical reactions to sounds. Unfortunately, sonochemistry already exists, so we’re using music instead and calling it “echochemistry”.
Like so many good stories, this one begins on a Friday afternoon. Pete was rushing to finish his lab work, hoping to make it to the biannual West Failure trivia night at The King’s Kneecap. Earlier in the afternoon, he’d set up a Grignard reaction (the old-fashioned way), hoping to dump in his electrophile at 5 pm and bugger off down the pub. Just as he began washing up, he noticed that the reaction had not initiated. Pete added a pinch of iodine, while checking the time furtively. Nothing. More iodine elicited no response, so he tried Br2, then TMSCl, then dibromoethane, then heating and finally abuse, all without effect. Exasperated, our hero exclaimed “Well fuck it then, guess this is a Monday-Pete problem. Should have known better than to do this on a Friday-avo.” He returned to his mountain of dirty glassware, pausing only to queue up “Livin’ on a Prayer” on the stereo and max the volume. While blasting out the lyrics to this classic cleaning-up song, Pete shut down the lab. On his final paranoia-suppression walkaround, he noticed that his Grignard reaction was merrily boiling away. Perplexed, Pete pondered if pounding pop-songs had prompted his product to proliferate. Then he went to the pub and forgot all about it.
Returning to work on Monday, Pete discovered that his reaction was now an ethereal suspension of magnesium hydroxide, as he had left it stirring under house-nitrogen2 for the whole weekend. Resigned, he set the reaction up again, only to encounter the same lack of reactivity, and the same solution. Playing Bon Jovi made Pete’s Grignard reaction work better. We hypothesised two explanations for this effect: 1) This absolute banger was capable of providing motivation on a molecular level, or 2) thumping bass was eliciting an effect similar to sonication and helping to dislodge the oxide layer from the Mg turnings. Some further investigation eliminated the first explanation: Shia Labeouf’s “just do it” talk was completely ineffective while “bangarang” initiated the reaction. We tested a number of classic songs and ascertained that a strong bass line was essential to initiate the Grignard reaction (scheme 1). For example, “Smoke on the Water” and “Feel Good Inc.” produced good yields of 2, while Vivaldi’s “Four Seasons” gave only trace amounts of product. For a more complete control experiment, we used John Cage’s 4’33’’
Intrigued by the potential of this new field of echocatalysis to help us stick one to Phil Desolate, we chose to investigate further (in the hopes that we can commercialise it). Our first task was to find a more efficient way to introduce sound into our reactions. Figure 1 shows a selection of techniques tested, with the yield of 2 as a model system.
Starting with a measly 20% yield for a reaction catalysed by the lab stereo, we postulated that bringing the music source closer to the reaction would amplify the effect. Initially, we took this idea to the extreme by suspending small speakers in the reaction mixture. This was ineffectual, as the speakers rapidly dissolved in the solvent, giving a mixture measuring in at 9 on the Browning Index.3 We took a step back by placing the speakers inside the fume hood, which was meet with an increase in yield. A happy medium was found by fitting over-ear headphones to a round bottom flask. This technique provides a convenient, cheap, and rapidly assembled solution for echocatalysis, and should open make the field to chemists from all backgrounds. Therefore, we needed to find a way of making it vastly more expensive and exclusive, to help us carve out a lasting niche and rake in the profits. We collaborated with IKEA to design an echochemical reactor. The culmination of our efforts is shown in figure 2. We call it: The “Echosyn”.
The Echosyn consists of a standard magnetic stirrer with an overhead speaker mounted above the sample vial. The Mk. 1 Echosyn retails for just under $50,000, with extra accessories available for when you break the originals. Once we had this exorbitant apparatus in hand, we found ourselves in desperate need of justification for its existence. Extensive head scratching on this topic produced an intriguing shower-thought: what if we could play a sound with the resonant frequency of a particular chemical bond? Could we not activate a single bond within a complex molecule with a finely tuned burst of sound? Well, no. That’s the simple answer. Chemical bonds vibrate at around 50 THz while human hearing reaches only as far as 20 kHz. But we never let facts get in the way of a good story. Point being, we were going to need a very high note to activate a chemical bond. We chose diester 3 as our test molecule, as we happened to have lots of it lying around. Upon exposure to a Grignard reagent under traditional reaction conditions, 3 is susceptible to an addition reaction at either the 2 or 3 position (scheme 2). Even doing the reaction in a ball mill cannot rectify the lack of selectivity inerrant in this shitty transformation (vide supportus). None the less, we fired up the Echosyn and primed it with a playlist of the highest-pitched tracks we had on hand.
The first CD on the pile was A-Ha, which failed to impart any selectivity to the reaction, or improve our standing with the Birchtwig lab down the corridor. Aretha Franklin also proved incapable of improving the yield of 4a, and Kate Bush prompted the reaction to spontaneously combust. Initial results with Maria Carey were promising until the reaction vessel reached resonant frequency and shattered. As a last-ditch effort, we played Whitney Houston’s cover of “I Will Always Love You” at full volume. To our immense relief, we obtained exceptional selectivity for alcohol 4b. Evidently, we had found the resonant frequency for one of the two C=O bonds in 3. Why diester 3 should have such an affinity for the music of Whitney Houston, we can only guess.
Echocatalytic Reduction of Dinitrogen
If we’re going to beat Phil Desolate to a Nobel Prize, we felt we needed a more dramatic display of the power of echocatalysis. Aiming high, we set our eyes on the strongest bond in chemistry: N ≡ N. With an energy higher than 900 kJ/mol, it takes lithium metal, bizarre metal complexes or biological enzymy stuff4 to cleave this bond. Therefore, we resorted to the ultimate authority on broken bonds: Adele.
Our initial with attempts with conventional iron and molybdenum systems were met with very limited success (they failed completely), forcing us to design a new catalyst. We prepared a bidentate phosphine ligand featuring electron-rich futyl groups and an echophore, linked by a cyclobutene. These echophoric cyanoalkynes absorb sound waves and transmit the vibrational energy to the metal centre (probably). To add novelty, vanadium was selected as the metal (scheme 3).
Most of Adele’s work proved to be effective in fixing dinitrogen at room temperature, with turnover numbers ranging from 19 to 30. ‘Skyfall” was found to be the most effective song for this reaction, which seems only appropriate. Even with the enhancement offered by echocatalysis, it’ll be a while before this is economically viable.
Radical Cascade Cyclisation
As a final demonstration of the powers of echocatalysis, we explored its utility in a radical cascade-cyclisation. We envisaged that a Liszt- Tchaikovsky rearrangement of obstannane 6 could provide rapid access to the natural product [9.2.5]-dolipartone (7).5 This transformation is hampered by issues of selectivity, however, as a ketone and one alkene must remain untouched while two electronically-similar olefins must undergo radical scission-fission. We hypothesised that echochemistry might help us overcome this barrier, by selectively activating the required portions of 6. Cyclic echometry was used to determine the resonant frequencies of the C=C, C-I, C=O and C-Sn bonds in 6, which are displayed in scheme 4.6 Thus, to selectively cyclise 6 we needed a tune containing the notes E♭, C, A♭, and G♭, while avoiding B♮ and D♮. This constraint led us to screen a selection of songs written in the key of D-flat major.
Our investigation began with the third movement of Claud Debussy’s Suite Bergamasque: Clair de lune. When we exposed 6 to this 20th century classic, we were delighted to obtain [9.2.5]-dolipartone in 34% yield. This was increased to 57% by switching to Liszt’s 3rd Consolation. For a laugh, we tested the seminal work of the Russo-Austro-Italian composer Richtenburg Zellitofsgomanovicovich Percoffeov-popenofftershops: La Fantasia del pumpelmo. By the time this 73-movement epic was finished, the starting material had completely decomposed. The best results were obtained with a rendition Mozart’s seventh symphony in D♭-major. Mozart’s Moonlight Frittata was ineffective, probably because it doesn’t exist.
Conclusion and Future Work Echocatalysis is a versatile new tool for the synthetic chemist, so on so forth waffle waffle give us funding. Future studies by our group will investigate the possibility of blackmailing reactions into proceeding by playing “baby shark” on repeat, and the viability of work-out music for kinetic rate enhancement. Though not technically related to this paper, we have noted that in parallel to the inclusion of music in chemistry, there has been a recent shift towards chemistry in popular music. Table 1 contains a selection of our favourite chemical tunes.
In conclusion, we’re no strangers to catalysis. You’re familiar with Ingold’s rules, as are we. A comprehensive study’s what we’re thinking, which it unlikely to result from another group. This paper aims to inform the community of our feelings on this matter, and to help them understand that we’re…
NEVER GONNA GIVE YOU UP, NEVER GONNA LET YOU DOWN, NEVER GONNA RUN AROUND AND DESERT YOU!!! NEVER GONNA MAKE YOU CRY, NEVER GONNA SAY GOODBYE NEVER GONNA TELL A LIE AND HURT YOU!!!
P.T, F.C, J.S, E.G, J.P and A.M. played background music while G.S. prepared the manuscript.
*The supporting information is currently undergoing maintenance, but we can offer a replacement spectral service, which is a collection of random NMR’s lifted from the journal Dolphin Transactions. Reviewer 2 never noticed.
Notes and references
- There is no reference 1, but we can’t be arsed renumbering.
- “House nitrogen” refers to the “inert” gas supply plumbed into the fume hoods of many laboratories. Its composition is variable, and it often contains O2, H2O and CO2.
- K. Kahverengi, M. Mierda, R. Braun, G. Schlonk, 2021, J. Immat. Sci. 1, 10–12.
- B. I. Ology et al. 2020, Cells N. Stuff, 45, 183495–183496.
- D. R. Parton, 1980, J. Mus. Chem. 23, 1.
- Cyclic Echometry is like cyclic voltammetry, but instead of drawing a duck, it just sounds like one.
- B. L. Black, M. Bianco, F. Katzenjammer, 2002, J. Black. Chem. S2E1, 13:22.