Beta Elimination Reactions

Tutorial Created with Software Release: 2024-1
Topics: Catalysis & Reactivity, Energy Capture & Storage, Thin Film Processing
Methodology: Molecular Quantum Mechanics
Products Used: Jaguar, MS Maestro

Tutorial files

0.4 MB
This tutorial is written for use with a 3-button mouse with a scroll wheel.
Words found in the Glossary of Terms are shown like this: Workspacethe 3D display area in the center of the main window, where molecular structures are displayed

 

Tip: You can hover over a glossary term to display its definition. You can click on an image to expand it in the page.
Abstract:

 

In this tutorial, we will demonstrate the beta elimination reactions panel, which automates the calculation of energies for the elimination of H-X products from a reactant, where a H atom is at the beta position relative to the X atom in the reactant.

 

Tutorial Content

  1. Introduction to Beta Elimination Reactions

  1. Creating Projects and Importing Structures

  1. Elimination Reactions for A Simple Organic Molecule 

  1. Elimination Reactions with Stereochemistry Implications

  1. Elimination Reactions of Relevance to Catalysis

  1. Conclusion and References

  1. Glossary of Terms

1. Introduction to Beta Elimination Reactions

Beta elimination reactions are prevalent decomposition pathways in organic and organometallic chemistry in which typically two leaving groups combine and leave behind an unsaturated molecule.  They are also known as 1,2-eliminations, as the reverse of 1,2-addition reactions, since the two leaving groups are initially bound to adjacent atoms.  The mechanism is labeled E1 or E2 according to whether it is a unimolecular or bimolecular process.  Beta hydrogen elimination is the most common case, where H is at the beta position relative to another leaving group denoted X.

In organometallic chemistry, a classic example is beta hydrogen elimination from a metal alkyl (M-R) complex, eliminating an alkene and resulting in a metal hydride (M-H) complex.

In most cases of beta elimination, the stereochemistry of the products is unaffected by the elimination pathway, but in some instances, different stereochemical outputs arise depending on whether the elimination occurs via a syn-periplanar (sp) or anti-periplanar (ap) transition state.

The beta elimination panel automates the calculation of the energy of one or more elimination pathways for one or more input molecules, screening all possible elimination pathways as defined by the input parameters. You can specify which elements X (including H) to screen for elimination along with H, and whether the eliminations should proceed via syn-periplanar, anti-periplanar or both intermediates. Additionally, unoptimized intermediates for each elimination are provided, which are helpful for visualizing the reactions and can be used as inputs for transition state calculations (learn more about transition state calculations in the Locating Transition States: Part 1 tutorial).  

This workflow is useful for a number of applications, for example:

  • Predicting the thermal decomposition of precursors for chemical vapor deposition (CVD) or atomic layer deposition (ALD)
  • Predicting selectivity of metal catalysts towards beta hydrogen elimination or towards the reverse reaction, 1,2 olefin addition
  • Understanding various decomposition paths and their energies for molecules

In this tutorial, we will use the beta elimination reactions panel to predict the energy associated with the decomposition of several organic and organometallic molecules.

For reference documentation on the beta elimination reactions panel, see here. For a related workflow for calculating bond dissociation energy, the energy change associated with homolytically cleaving an R1-R2 bond into R1⦁ and R2⦁ radical fragments, see the Bond and Ligand Dissociation Energy tutorial.

2. Creating Projects and Importing Structures

At the start of the session, change the file path to your chosen Working Directorythe location where files are saved in MS Maestro to make file navigation easier. Each session in MS Maestro begins with a default Scratch Projecta temporary project in which work is not saved, closing a scratch project removes all current work and begins a new scratch project, which is not saved. A MS Maestro project stores all your data and has a .prj extension. A project may contain numerous entries corresponding to imported structures, as well as the output of modeling-related tasks. Once a project is saved, the project is automatically saved each time a change is made.

Structures can be built in MS Maestro or can be imported using File > Import Structures (or drag-and-dropped), and are added to the Entry Lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion and Project Tabledisplays the contents of a project and is also an interface for performing operations on selected entries, viewing properties, and organizing structures and data. The Entry Lista simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion is located to the left of the Workspacethe 3D display area in the center of the main window, where molecular structures are displayed. The Project Tabledisplays the contents of a project and is also an interface for performing operations on selected entries, viewing properties, and organizing structures and data can be accessed by Ctrl+T (Cmd+T) or Window > Project Table if you would like to see an expanded view of your project data.

  1. Double-click the Materials Science icon

Figure 2-1. Change Working Directory option.

  1. Go to File > Change Working Directory
  2. Find your directory, and click Choose
  3. Pre-generated input and results files are included for running jobs or examining output. Download the zip file here: schrodinger.com/sites/default/files/s3/release/current/Tutorials/zip/elimination_reactions.zip
  4. After downloading the zip file, unzip the contents in your Working Directory for ease of access throughout the tutorial

Figure 2-2. Save Project panel.

  1. Go to File > Save Project As
  2. Change the File name to elimination_reactions_tutorial, click Save
    • The project is now named elimination_reactions_tutorial.prj

Figure 2-3. Import the starting structures.

In the subsequent sections of this tutorial, we will analyze several molecules with the Beta Elimination Reactions panel. Let’s import these structures now:

  1. Go to File > Import Structures
  2. Select input_molecules.mae
  3. Click Open
    • A new entry group is added to the entry list containing four entries

Note: These structures have not yet been optimized at the quantum mechanical level. The workflow used herein includes that process.

Note: If you would prefer to prepare these input molecules yourself as you go, feel free to do so. The three organic molecules are easily drawn with the 2D Sketcher and the organometallic complex can be built with the Single Complex Builder. See the Introduction to Materials Science Maestro tutorial for details on how to do so.

3. Elimination Reactions for a Simple Organic Molecule

We will begin by analyzing bromoisopropane (2-bromopropane), a simple organic molecule with two possible beta hydrogen elimination products (excluding H2 elimination): loss of CH4 or loss of HBr. Suppose we want to automatically compute the reaction energies associated with both eliminations, compare these energies and thus answer the question: what is the most likely beta hydrogen decomposition pathway for this molecule?

Figure 3-1. Select and include the bromo-isopropane entry and open the panel.

  1. Select(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries and includethe entry is represented in the Workspace, the circle in the In column is blue the bromo-isopropane entry from the entry list
  2. Go to Tasks > Materials > Quantum Mechanics > Workflows > Beta Elimination Reactions

 

Note: We will frequently use this panel in this tutorial. To make it easier to find the panel you can click the star next to the panel name in the task menu and it will be added as a favorite to your toolbar.

Figure 3-2. Set up the panel.

The panel requires only a few input parameters.

  1. Ensure that Use structures from is set to Project Table (1 selected entry)
  2. For Elements to eliminate with beta-H, change to C, Br
    • This will search the molecule for any possible unique C-H and Br-H beta eliminations
  3. For Elimination geometry, maintain the default Syn-periplanar, but note that in this case there are no stereochemical consequences of choosing the elimination geometry
    • Elimination will take place if the leaving groups can be rotated into this geometry, ignoring the constraints of the 1,2 bond
  4. Maintain the default Jaguar Options which are sufficient for this simple organic example

Note: An option for a machine learning force field (MLFF) is available as an alternative in the Jaguar Options. Additional information regarding MLFF can be found in the help documentation, on our website, or the Beta Elimination Reactions panel documentation.

Note: Include H as an element to eliminate with if you are interested in H2 elimination.

 

Figure 3-3. Preparing and running the job.

  1. Change the Job name to beta_elimination_bromoisopropane
  2. Adjust the job settings () as needed
    • This job requires a CPU host. The job can be completed in about 3 minutes on a 12 CPU host
  3. Click Run
  4. Close the Beta Elimination Reactions panel
These files are also available for importing in the provided tutorial files: go to File > Import Structures, navigate to where you downloaded the tutorial files, and Open Section_03 > beta_elimination_bromoisopropane > beta_elimination_bromoisopropane.maegz

Before analyzing the outputs, let’s take a moment to detail the Beta Elimination Reactions panel a bit further:

  • Elements to eliminate with beta-H define the H-X bonds to eliminate. The panel will open with all of the non-H elements in beta positions proposed by default.
  • Elimination geometry can be used to specify syn, anti or both elimination geometries, as described in Section 1.
  • Check the Generate intermediates option if you want to include entries that are approximations of intermediates of the reactions, which can be used to help visualize the reaction that is occurring.
  • Click the Review Reactions button if you want to preview the unoptimized structures that are going to be submitted for quantum mechanical (QM) calculations. This ‘dry-run’ tool is useful for summarizing the expected job at no computational cost before committing to potentially expensive jobs that may not be of interest.
  • Change the Jaguar Options if you wish to specify any specific parameters for the QM jobs, including functionals and basis sets (see the Introduction to Geometry Optimizations, Functionals and Basis Sets tutorial for more background) or to choose a machine learning force field (MLFF) instead.
  • Use the Custom reactions option to specify a reaction by importing the reactants and products -- the main use case for this option is for restarting a failed Jaguar optimization. Other uses are described in the help

Figure 3-4. The entry list after the job is complete. A product entry is included in the figure as an example.

When the job finishes or the structures have successfully imported, a banner will appear indicating that the output has been incorporated. A new entry group appears in the entry list titled bromo-isopropane (9), which contains several additional entry groups and nine entries.

Let’s first understand the contents of the output entry group:

  • The first entry, entitled CC(Br)C is the geometry optimized reactant, named with its SMILES string
  • Next, there are two entry groups CC(Br)C to C + BrC=C (4) and CC(Br)C to Br + CC=C (4), one for each of the possible reactions, again titled with their SMILES strings. Specifically, the first entry group is for hydrogen bromide elimination and the second is for methane elimination
  • Within each reaction group, there are four entries. First, the geometry-optimized products of the reactions: methane (C) and vinyl bromide (BrC=C), in the second case. Following the product entries are two additional entries that are not optimized geometries. These entries are approximations of intermediates of the reactions, which can be used to help visualize the reaction that is occurring.

Proceed to include the various entries to better understand the output until you are comfortable visually interpreting the results.

Figure 3-5. An approximate intermediate for the HBr elimination.

Let’s consider an intermediate entry a bit more:

  1. Include Product intermediate from the CC(Br) to Br + CC=C (4) reaction
    • An intermediate geometry from the reaction is shown in the workspace, with the new H-Br and C=C bonds drawn in, but clearly not optimized. This intermediate could be used as a starting point for a transition state calculation

For background and practice regarding transition state calculations, see the Locating Transition States: Part 1 tutorial

Figure 3-6. Analyzing the Project Table.

  1. Open the Project Table ()

Note that the geometry optimized entries now have Gas Phase Energy associated with them from the Jaguar calculation. Additionally, a new property has appeared entitled Beta Elimination Energy (kcal/mol). This property has values for any of the products, and represents the energy change for the corresponding reaction at T=0 K. In this case, both reactions are uphill by ~20-25 kcal/mol.  The more likely reaction is the one with the lower energy cost.  The data can be analyzed directly in the Project Table, or exported if you prefer.

4. Elimination Reactions with Stereochemistry Implications

Now that we are comfortable using the panel and interpreting the results, let’s look at a pair of molecules in which the elimination geometry is significant with respect to product stereochemistry. Specifically, we will perform the Beta Elimination Reactions workflow on a pair of enantiomers (shown below), in which different alkenes are generated depending on whether a syn or anti elimination proceeds.

Figure 4-1. Select both halobutane entries.

  1. Close the Project Table and select(1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries both halobutane_R-enantiomer and halobutane_S-enantiomer from the input_molecules (4) entry group in the entry list
    • Recall that selecting means to highlight the entry titles in the entry list

Figure 4-2. Labeling a stereocenter.

Optional: It is straightforward to label chiral centers as R or S using the Materials Science Maestro interface. To label the carbon in a molecule, includethe entry is represented in the Workspace, the circle in the In column is blue either reactant, go to Style > click the Arrow next to Apply Labels > click Chirality. The carbon is labeled R or S accordingly. Label fields can be extended to also label E/Z stereochemistry with the Add Label Fields capabilities 

Figure 4-3. Setting up the panel.

  1. Go to Tasks > Materials > Quantum Mechanics > Workflows > Beta Elimination Reactions
  2. For Use structures from, ensure that Project Table (2 selected entries) is displayed
    • Batch running is possible with this workflow. All selected structures will be run with same parameters simultaneously
  3. For Elements to eliminate with beta-H, input Br
    • This will restrict this example to only HBr elimination (excluding HF, HCl, CH4, etc.)
  4. For Elimination geometry, choose Both from the dropdown menu
  5. Change the Job name to beta_elimination_halo
  6. Adjust the job settings () as needed
    • This job requires a CPU host. The job can be completed in about 10 minutes on a 12 CPU host
  7. Click Run
  8. Close the Beta Elimination Reactions panel

Note: If you would prefer not to run the job, pre-generated results are available for import in the provided tutorial files, Section_04 > beta_elimination_halo > beta_elimination_halo.maegz

Figure 4-4. Output after incorporation, showing R enantiomer reactant included in the workspace.

The workflow automates the execution rather efficiently; only 5 DFT calculations are run despite four unique reactions occuring. When the job finishes, two new entry groups are incorporated (one for each enantiomer).

Proceed to analyze the output following the same steps as in the previous section.

Here are several key observations:

  • Elimination of HBr can produce two alkene isomers, denoted E and Z
  • For the R-enantiomer, the antiperiplanar elimination results in the CF3 groups on the same side of the double bond (E isomer) while the syn elimination results in the CF3 groups on opposite sides of the double bond (Z isomer)
  • Conversely, for the S-enantiomer, the anti-periplanar elimination results in the CF3 groups on opposite sides of the double bond (Z) while the syn elimination results in the CF3 groups on the same side of the double bond (E)
  • Analysis of the elimination energies indicates that formation of the E isomer product is slightly favored in terms of bonding

More complicated diastereomers can result in many interesting outcomes 

5. Elimination Reactions of Relevance to Catalysis

Elimination of an alkene from an organometallic complex is a classic beta elimination reaction, specifically referred to as beta hydrogen elimination. As a final example, let’s perform the workflow on a zirconium alkyl complex (a prototypical Ziegler-Natta catalyst). The eliminations studied here are of relevance to alkene polymerization catalysis, specifically, the polymerization process proceeds via the reverse of the elimination, i.e. 1-2 addition.

Figure 5-1. Setting up the panel for the Zr example.

  1. Select Zr_propyl_Cp_Cp_Cl
  2. Go to Tasks > Materials > Quantum Mechanics > Workflows > Beta Elimination Reactions
  3. For Use structures from, ensure that Project Table (1 selected entry) is displayed
  4. For Elements to eliminate with beta-H, input C, Cl
  5. For Elimination geometry, choose Syn-periplanar from the dropdown menu
    • Elimination from ligands attached to a metal center is typically syn-periplanar (via a four-membered-ring transition state)
  6. In the Jaguar Options, change Basis-set to LACVP**
    • This basis set is sufficient for standard optimizations of transition-metal containing species. See the Organometallic Complexes tutorial for more background.
  7. Change the Job name to beta_elimination_Zr

 

This job takes 60 minutes on a 12 CPU host. If you would like to run the job, adjust the job settings () as needed and click Run

  1. Otherwise, close the Beta Elimination Reactions panel and we will proceed to import pre-generated results

Figure 5-2. Output after importing or incorporation.

  1. Go to File > Import Structures
  2. Select Section_05 > beta_elimination_Zr > beta_elimination_Zr.maegz
  3. Click Open
    • A new entry group containing 13 entries is added to the entry list

Figure 5-3. The unoptimized intermediate for beta hydrogen elimination, useful for locating the transition state.

Proceed to analyze the output following the same steps as in the previous section.

Here are several key observations:

  • Three reactions are found with this set of input parameters
  • All of the elimination energies are positive at T = 0 K and, from the magnitude of the energies, likely none of these processes will occur under homogeneous catalysis conditions
  • The third reaction is the elimination of the alkene (SMILES string C=C) and costs +19.8 kcal/mol. The reverse reaction is the 1,2-addition of ethylene into the Zr-CH3 bond that occurs in Ziegler-Natta polymerization, which therefore has an internal energy change of -19.8 kcal/mol (i.e. exoergic at T = 0 K)

The unoptimized intermediate structures are quite useful in this case as starting structures for transition state calculations. For example, the insertion of ethylene into the Zr-CH3 bond is shown in the figure and is suitable for a transition state job

6. Conclusion and References

In this tutorial, we learned to use the beta elimination reactions panel as an efficient workflow for calculating energies for various H-X (X = any element including H) elimination reactions. 

For further learning:

For introductory content, focused on navigating the Schrödinger Materials Science interface, an Introduction to Materials Science Maestro tutorial is available. Please visit the materials science training website for access to 70+ tutorials. For scientific inquiries or technical troubleshooting, submit a ticket to our Technical Support Scientists at help@schrodinger.com. 

For self-paced, asynchronous, online courses in Materials Science modeling, including access to Schrödinger software, please visit the Schrödinger Online Learning portal on our website.

For some related practice, proceed to explore other relevant tutorials:

7. Glossary of Terms

Entry List - a simplified view of the Project Table that allows you to perform basic operations such as selection and inclusion

Included - the entry is represented in the Workspace, the circle in the In column is blue

Project Table - displays the contents of a project and is also an interface for performing operations on selected entries, viewing properties, and organizing structures and data

Scratch Project - a temporary project in which work is not saved, closing a scratch project removes all current work and begins a new scratch project

Selected - (1) the atoms are chosen in the Workspace. These atoms are referred to as "the selection" or "the atom selection". Workspace operations are performed on the selected atoms. (2) The entry is chosen in the Entry List (and Project Table) and the row for the entry is highlighted. Project operations are performed on all selected entries

Working Directory - the location where files are saved

Workspace - the 3D display area in the center of the main window, where molecular structures are displayed