Future of

Computational
Chemistry in
Organic Reactions
Group # 4
Made by:

Daniya Arif (KFCACHEM201101039)

Arisha Akram (KFCACHEM201101004)
Zunaira Salamat (KFCACHEM201101051)
Aweza Abdul Malik (KFCECHEM201101048)
Physical Chemistry Quantum Chemistry Computational Chemistry

Computational Chemistry:
Computational Chemistry, within the discipline of theoretical chemistry, is a branch of chemistry which
focuses mostly on using computations to solve problems connected to chemistry.(Jensen, 2017)

Difference between Computational and Theoretical Chemistry:

Theoretical Chemistry: Computational Chemistry:
Mathematical methods combined with fundamental laws Subfield of Theoretical Chemistry where problems are
of Physics to study the processes of chemical relevance. solved by friendly computer programs.

“If you can just draw the molecule on the screen, you can run the calculations on it
(semi empirical, ab initio, DFT)”
Importance of Computational Chemistry:

 Drug Design and Discovery

 Molecular Modeling

 Catalysis

 Quantum Chemistry

 Polymer Chains

 Chemical Kinetics

 Environmental Chemistry

 Computing Spectroscopy Graphs

 Forensic Science
Why Computational Chemistry Is Better Than Theoretical
Chemistry?
There are various problems in chemistry and various other sciences that theoretical chemistry can’t solve, but
computational chemistry give their effective solutions. Some of the problems are given here:

Theoretical Chemistry can’t give valuable information about the geometries and shapes of molecules.
Computational Chemistry make it possible to detect geometries of molecules and can predict it’s involvement
in further reactions.

• A computational model of a molecule is given below:

• Spectra's are analyzed and predicted by Computer:

• Molecular Study of Corona Virus:

Molecular Model of
COVID-19

Structure of SARS
Virus
Need of Computational Chemistry:
"Making predictions is hard, especially when they involve the future."

Computational Chemistry is needed to answer the following questions:

What possible products might arise? Which one will be the main product? Which reaction condition could be best for the
putative primary product? What is the purported major product's potential yield? What synthetic route could be used to
synthesize it using the reaction building blocks that are now on hand? How can these potential synthetic procedures be
ranked and filtered based on user-specified criteria? What could the main steps in the mechanistic reaction be? Which key
elements influence product yield or stereoselectivity and regioselectivity?

Terms used in Computational Chemistry:

In Silico:
Ab initio:
Predictions by
From the
using
beginning
Computers.
Density Functional Theory:

Density Functional Theory (DFT) is a quantum mechanical method used to investigate the electronic structure (principally
the ground state) of many-body systems, particularly atoms, molecules, and condensed phases. DFT is widely applied in
physics, chemistry, and materials science due to its balance between accuracy and computational cost.
Density Functional Theory is a powerful and versatile method in computational chemistry, enabling the study of a wide
range of chemical and physical phenomena with reasonable computational resources. Its development has significantly
advanced our ability to understand and predict the behavior of complex systems at the atomic level
Computational Softwares:

• Gaussian: Used for electronic structure modeling, including molecular geometries, energies, and vibrational
frequencies.

• ORCA: An efficient tool for quantum chemistry calculations.

• Spartan: Provides tools for molecular mechanics, semi-empirical methods, density functional theory (DFT), and ab
initio calculations. Useful for studying organic molecules, reaction mechanisms, and molecular properties.

• GAMESS(General Atomic and Molecular Electronic Structure System): Performs a wide range of quantum chemical
calculations including Hartree-Fock, DFT, and post-Hartree-Fock methods. Suitable for electronic structure analysis of
organic molecules.

• ADF(Amsterdam Density Functional): Specializes in handling large molecular systems and periodic structures. Used for
electronic structure calculations, reaction mechanisms, and spectroscopic properties of organic molecules.

• J-Sim(Java Simulations for Chemistry): Focuses on NMR spectroscopy with user-friendly simulation and visualization
capabilities.
Role of Computational Chemistry in Broad Organic Branches:
1. Selectivity in Organic Reactions

2. Organic Catalysis

3. Polymer Chemistry

4. Organic Spectroscopy

5. Quantum Chemistry

6. Retrosynthesis

7. Future of Computational Chemistry

8. ChemDraw
Selectivity in Organic Reactions:

• Stereoselectivity: • Chemo-Selectivity: • Stereospecificity:

In chemistry, stereoselectivity is the
property of a chemical reaction in
which a single reactant forms an
unequal mixture of stereoisomers.
Br
A reaction that operates exclusively A stereospecific reaction is one in
on one functional group in the which there is only one possible
presence of other functional stereochemical outcome for the
groups. product and that outcome is
controlled by the stereochemistry of
the reactant.
NH2 NHAc

Br
HOAc H3C Br
-HBr +
Pyridine NaOH CH3
Major Minor
H
Et Et H
OH OH
Role of Computational Chemistry in Selectivity of Organic
Reactions:

• Computational chemistry helps elucidate the reaction pathways, including intermediates and transition

states.

• Computational methods can calculate the relative energies of different stereoisomers by calculating the

reactivity of different functional groups within a molecule.

• Computational chemistry can predict which functional group is more likely to react under given conditions,

aiding in chemo-selective synthesis.

Organic Catalysis:

“Catalysis is the increase in rate of a chemical reaction due to an added substance known as a
catalyst”
Catalyst:

“A catalyst is any substance that increases the rate of a reaction without itself being consumed”

Role of Computational Chemistry:

• Computational methods can map out the entire catalytic cycle, identifying intermediates and transition
states. This helps in understanding how the catalyst facilitates the reaction and the steps involved.
• By modeling the electronic structure of the catalyst's active site, computational chemistry helps to identify
the key features that contribute to catalytic activity.
• For heterogeneous catalysts, computational methods can study the surface properties and how these

influence catalytic activity and selectivity.

• Computational tools can model the kinetics of catalytic reactions, providing insights into reaction rates and

mechanisms.
Polymer Chemistry:

“The area of chemistry that deals with the study of polymers”

Polymers:

“The type of macromolecular substances that are made of repeating units called
monomers”(mono=one, mers=units)

Common example of polymer is: Polystyrene, which is commonly used in daily life.
Role of Computational Chemistry:

• Thousands or perhaps millions of atoms joined chemically in a repeating pattern make up a polymer

molecule or chain, can be identified by Computations.

• Computational chemistry plays a crucial role in the study of polymers by providing insights into their

structure, properties, behavior, and interactions at the molecular level.

• Modeling can explore the stereoregularity of polymer chains (isotactic, syndiotactic, atactic), which affects

properties like crystallinity and mechanical strength.

Model to Represent Polymers:
Coarse-Grained (CG) Models

Polymer chain CG models consist of "beads" where each bead, which is often spherical, represents a section of the
polymer chains. (Gartner III & Jayaraman, 2019)
Organic Spectroscopy:

• Organic spectroscopy relies on the principles of energy absorption, emission, or scattering of light by

molecules. When a molecule interacts with electromagnetic radiation, it undergoes transitions between

different energy states, resulting in the absorption or emission of photons.

There are various types of Organic spectroscopy such as UV-Visible Spectroscopy, IR Spectroscopy, Raman
Spectroscopy, NMR Spectroscopy and NQR Spectroscopy etc.

Role of Computational Chemistry in Organic Spectroscopy:

• NMR Spectroscopy: Computational methods can predict NMR chemical shifts, coupling constants, and
spectra for organic molecules. This helps in identifying molecular structures, conformational analysis, and
studying interactions with solvents or ligands.

• IR Spectroscopy: Calculation of infrared spectra helps in identifying functional groups, studying hydrogen
bonding, and understanding molecular vibrations.

• UV-Vis Spectroscopy: Predicting electronic spectra and transitions aids in understanding conjugation,
chromophores, and the absorption properties of organic molecules.
• Raman Spectroscopy: Computational approaches can simulate Raman spectra, providing information
about molecular vibrations and structural properties.
Quantum Chemistry:

“Quantum Chemistry is a theoretical analysis of protons, neutrons, and electrons as well as the
electronic structure and molecular dynamics”

Role of Computational Chemistry in Quantum World:

• Quantum Mechanical Methods: Computational chemistry employs various quantum mechanical methods to
calculate the electronic structure of atoms, molecules, and solids
• Solve the Schrödinger equation without approximations, providing highly accurate results but requiring significant
computational resources.
• Computational chemistry within quantum chemistry plays a pivotal role in advancing our understanding
of chemical systems and processes.
Retrosynthesis:

“Retrosynthesis is the process of “deconstructing” a target molecule into readily available starting materials
by means of imaginary breaking of bonds”
Another definition is:

"A problem-solving technique for transforming the structure of a synthetic target molecule to a sequence of
progressively simpler structures along a pathway which ultimately leads to simple or commercially available starting
materials for a chemical synthesis"

Role of Computational Chemistry in Retrosynthesis:

• Reaction Database: Computational tools can search extensive databases of known reactions to propose
feasible transformations that can be used in retrosynthetic planning.
• Modeling can assess the economic feasibility and environmental impact of different synthetic routes,
considering factors like solvent usage and waste generation.
• Mostly used software for retrosynthesis are:
o SYNTHIA.
o IBM RXN for Chemistry.
Future of Computational Chemistry:

“The computations that will be possible in future will be largely dependent on how
software (algorithms and techniques) and computer hardware progress in the future”

The future of computational chemistry in organic reactions promises to revolutionize how chemists design,
optimize, and understand chemical transformations at the molecular level.

Computational chemistry is poised to become even more predictive in designing organic reactions. Advances
in quantum mechanical methods, such as density functional theory (DFT) and ab initio calculations, will
continue to enhance accuracy in predicting reaction mechanisms, transition states, and reaction energetics.
This predictive capability will enable chemists to explore novel chemical spaces and discover reactions that
were previously overlooked or deemed impractical.
AI-driven tools will analyze vast databases of reactions, learning from historical data to propose efficient
synthetic routes and optimize reaction conditions. This automation will not only speed up the discovery
process but also reduce the reliance on serendipity in finding new reactions.

Conclusion:
By harnessing computational power, predictive algorithms, and interdisciplinary collaboration, researchers will
unlock new frontiers in chemistry, leading to innovative technologies, sustainable practices, and
breakthroughs in human health and well-being. As these advancements unfold, computational chemistry will
continue to be at the forefront of driving scientific discovery and societal progress in the next century.
THANKS & REGARDS
DANIYA ARIF
BS CHEMISTRY

KFC COLLEGE RYK