AB INITIO STUDY OF HOFMANN LÖFFLER REACTION WITH AND WITHOUT IODINE CATALYST ON INGENINE E MOLECULE

• Main Author: Arifah, Aminatus
• Format: Theses
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/62583
• Institution: Institut Teknologi Bandung

Hofmann Löffler reaction was cyclization reaction involving nitrogen radical species to produce products in the form of pyrrolidin or piperidine. This nitrogen radical species was formed through homolytic bond breaking process using photons and the help of concentrated strong acids. The use of concentrated strong acid was often incompatible for various sensitive functional groups, so modification was made using iodine catalyst to prevent side reactions. The modification of the Hofmann Löffler reaction mechanism using iodine catalyst had not been studied energetically therefore studies on the reaction mechanism were still minimal. Therefore, it was prominent to study mechanism of the Hofmann Löffler reaction using iodine catalyst, one of that was throught computational study. Computational studies on the Hofmann Löffler reaction using iodine catalyst and without iodine catalyst had been carried out in this thesis using ingenina E as reagent. Ingenina E was molecule derived from the species Acanthostrongylophora ingens and was species originating from Indonesian ocean. Ingenina E was molecule that discovered in 2016 so the utilization of this ingenina E molecule was still minimal. The study of ingenina E as reactant for the Hofmann Löffler reaction on this computational study was expected to increase the usefulness of the ingenina E molecule for the synthesis of other. The computational study was carried out through geometric optimization using the DFT (density functional theory) and B3LYP (Becke's three- parameters exchange functional) functional methods. The base set used was def2/SVP using ORCA software. The search for the transition state was carried out using the geom scan method, the sadlle method, and one point calculation. Solvent modeling was carried out using the CPCM (Conductor-like polarizable continuum model) method with dichloromethane as solvent. The analysis results of the dichloromethane solvent effect on the Hofmann Löffler reaction mechanism without catalyst indicate that the presence of solvent stabilizes molecular energy, especially in anion species through ion-dipole interactions. Meanwhile, the solvent influence on neutral molecule results was lower stabilization because the interaction that occurred was dipole-dipole interaction. Based on the optimization results of Hofmann Löffler reaction without catalyst, the step that required the highest energy was the formation of carbon radicals. The results transition state in the hydrogen atom transfer process and the cyclization process indicated that the hydrogen atom transfer process was the step that determined the rate of the reaction. The optimization results of the Hofmann Löffler reaction using iodine catalyst indicated step that required the highest energy was the formation of NBS radicals. While the search for transition states in the process of forming carbon radicals and the cyclization process shown that rate determined step was the formation of carbon radicals. In addition, based on the results of geometric optimization, the Hofmann Löffler reaction mechanism using iodine catalyst in the formation of iodine-NBS was difficult, another alternative was through the formation of Br-iodine molecules. Based on geometric optimization of several possible reactions, the Hofmann Löffler reaction mechanism without catalyst and with iodine catalyst shown that both produced products with the lowest energy in the formation of (R)-1-methyl-5(9H- pyrido[3,4-b]indole -1-yl)pyrrolidin-2-one. Overall, to form the same product, the Hofmann Löffler reaction using iodine catalyst required lower energy than the Hofmann Löffler reaction without catalyst, especially in the cyclization step. The product with the lowest energy, (R)-1-methyl-5(9H-pyrido[3,4-b]indole-1- yl)pyrrolidin-2-one had one chiral C atom, so further analysis was needed to determine a more detailed configuration. Further analysis of the chiral C atom through geometry optimization and the transition state of Hofmann Löffler reaction using an iodine catalyst showed that neither the R configuration nor the S configuration had significant energy difference so the product was formed as racemic mixture.