To understand this, we calculated for the LUMO Map, which is a superposition of LUMO and Electron Density Map of the molecule. Then why treatment of 2,4-dichloro-5-methylpyrimidine with n-butyllithium affords only the C-6 addition product? It is the same substrate, same LUMO. That leads to the overall transformation we observed (Figure 3).įigure 3. Reversible and irreversible interaction of piperidine and 2,4-dichloro-5-methylpyrimidine at C-6 and C-4 positions. Moreover, addition of piperidine at C-6 site is reversible, while addition at C-4 site will lead to displacement of the chloro group, an irreversible event. Whereas at C-4 and C-6, both have LUMO lobes associated with them, as such these LUMO lobes will be able to interact with incoming nucleophiles. Notice that there is no LUMO lobe over C-2, as such, accounting for no displacement reaction observed at this carbon. Middle: LUMO superimposed onto ball & stick model.) LUMO lobe of 2,4-dichloro-5-methylpyrimidine (Left: Molecular Orbital energy level. Our laboratory chemists prefer to use Spartan, which has a user-friendly graphic interface, making calculations relatively easy to set up and the results easier to interpret.įirst, let’s calculate the LUMO and its associated orbital energies of 2,4-dichloro-5methylpyrimidine (the electrophile in the reaction) with Spartan (Figure 2).įigure 2. There are a number of powerful QM computing tools available to us. Now let’s use FMO theory to rationalize the aforementioned nucleophilic reactions with the dichloropyrimidine (Figure 1). It enables chemists to understand how orbitals interact with one another throughout the course reactions, and to account for chemical reactivity & selectivity observed, etc. Based on FMO theory, an organic reaction is electron transfer from nucleophilic part (HOMO) to the electrophilic part (LUMO) of the reacting system. For organic reaction, we could focus on the use of Frontier Molecular Orbital (FMO) Theory, which emphasizes the analyses with outer orbitals, i.e., Highest Occupied Molecular Orbital (HOMO) and the Lowest Unoccupied Molecular Orbital (LUMO). These orbitals have their own energy levels and unique spatial distribution. Frontier Molecular Orbital Theory (FMO)įirst let's review the basics of Molecular Orbital (MO) Theory, which proposes that when atoms come together to constitute a molecule, their atomic orbitals interact with each other and form new molecular orbitals. You will see that it is relatively easy to understand and apply QM in your laboratories. In this article, we will discuss how we use LUMO and LUMO Map to analyze nucleophilic aromatic substitution reactions. The question becomes “What could be the best scientific method to rationalize, to learn these chemistry?” In our synthetic organic chemistry laboratories, we found QM to be the most valid and efficient tool for these purposes. Nucleophilic reaction of 2,4-dichloro-5-methylpyrimidine with alkyl lithium or aliphatic amine Why is it not the case? We also observed that when the nucleophile is alkyllithium, a C-6 addition product is observed instead of C-4 displacement of chloride. Intuitively it makes more sense for the substitution to occur faster at C-2, which has two electron withdrawing aromatic nitrogen atoms next to it. We learned that nucleophilic substitution of 2,4-dichloro-5-methylpyrimidine with a nucleophile, such as piperidine, proceeds preferentially at C-4 position (Figure 1). Please join us to unleash the magical power of Quantum Mechanics (QM).
![lumo orbital lumo orbital](https://www.studyorgo.com/blog/wp-content/uploads/2016/06/MO-2.jpg)
Would you prefer to learn and rationalize organic chemistry in a data-driven manner? Would you like to predict organic reaction outcomes accurately? Design synthetic sequences with higher rate of success? Application of LUMO in Nucleophilic Reactions QM Magic Class | Chapter 1