In a general acid catalyzed reaction the rate determining step in the reaction is the proton transfer.  Until recently the means to map the potential energy surfaces (PES) for general acid catlyzed reactions have not been available because the kinetics of this type of reaction occur on a very fast time scale.  The current technology makes it possible to use computational methods to map the PES using small model compounds.  Eventually this information will be used as a guide for future experiments using high powered, finely tuned lasers to overcome the barrier that makes the proton transfer the rate determining step after the molecules are hydrogen bonded.  In this paper will discuss how the best proton donor/acceptor combination was selected using semi-empirical and Hartree-Fock (HF) as methods to model a PES in general acid catalysis. The proton donors that were used in the calculations were NH₄⁺ and H₃O⁺, while the proton acceptors included simple ortho esters and iranes.
 
 

   The control of chemical reactions has been the Holy Grail for chemists since the time of the alchemists.  Over the years much has been learned about how to control the conditions to make a reaction proceed more efficiently, but not until recently has there been any type of direct manipulation of the molecules to control the reaction.
    With the introduction of high-powered, short-pulsed lasers in the 1980ís, it has become possible to control the motions of the molecules themselves.  Zewail, Zare, Crim, and many others including Dantus here at Michigan State University have done work in this area.
   All the work in this field so far has been done in the gas phase and in very specialized conditions, like isolating single molecules.  However, most chemistry is done in bulk and in the liquid phase.  Our work hopes to find a set of reactions that are controllable in the liquid phase that will not need very specialized conditions.  As will be discussed in this poster, general acid catalysis is a good candidate for a reaction that may be controllable in the liquid phase in bulk.

   In acid catalysis the catalysts are oxonium ions resulting from the dissociation of the acid in the solvent, which in most cases is water; but can include all proton acceptors and donors in the solution.  Weak acids produce two types of acid catalysis.  They are known as general and specific.  They differ in which proton donors and acceptors are considered part of the catalyst.
    In general acid catalysis, the form that is the basis of this project, all proton acceptors and donors are included in the catalysis, hence the name general.  In other words it is dependent on total acid concentration, not just pH.  The proton transfer from the donor to the acceptor is the rate-limiting step in this type of catalysis.  Once this energy barrier is overcome, the rest of this reaction proceeds rapidly.
   In the other type of acid catalysis, specific acid catalysis, the rate-determining step is not the proton transfer.  Overcoming the energy barrier for this transfer does not make the reaction proceed rapidly like in general acid catalysis.  It is dependent on only the pH, or the concentration of the specific acid, oxonium or the H⁺ species.
 
 

    Since this reaction has proton transfer as its rate determining step, it may be possible to control the reaction by finding way to give the hydrogen-bonded complex just enough energy to overcome the proton-transfer-energy barrier or arrive at an energy level where proton can tunnel though the energy barrier.  The hydrogen-bonded complex holds the proton donor and acceptor in the right configuration to transfer the proton.  If the one can selectively break the hydrogen bond between the proton and the donor, it will be possible to control this reaction.  This is because once this occurs the reaction proceeds rapidly.
   Knowing the shape of the potential energy surface (PES) for a general acid catalyzed reaction will show us what the energy barrier looks like.  This information will help us set up experiments to show that proton transfer can be controlled in a general acid catalyzed system.  It will help to select the laser, which will be used to deliver the exact amount of energy to overcome the barrier and will help with selecting molecules that can be studied this way.
 
 

   The fast kinetics is why the potential energy surface for general acid catalysis has not been studied experimentally. However, advances in computer technology have made it possible to do calculations to predict the structure of the intermediates in a timely manner, even on a personal computer.  These advances have also increased the information storage capabilities.  This is very important because the contributions of several orbitals on each atom to the energy of the molecule(s) must be included in each step of the calculation and saved.  Calculations improve in accuracy as the number of orbitals included in the calculation increases. This basic structural information and information on how the structure is changing as the calculation proceeds can take up megabytes (MB) of storage space.
 
 

   Ortho esters, such as 2-methoxy-1,3-dioxolane, were first used for the calculations because they are known to undergo general acid catalysis and are available through commercial means.  This is important for the experimental work since there should be an accessible supple of sample.
  The molecules for this PES calculation were chosen because they were smallest that could be used for ortho ester general acid catalysis.  Since every atom in has several orbitals, more computer time and space would be needed as the molecules became larger.  This also added to the complexity of the calculation since the orbitals interact with one another.
   A semi-empirical method, PM3, was used to make this PES.  Semi-empirical methods utilize experimental values and simple basis sets, mathematical functions describing orbitals, to calculate the energies of the molecular configurations.

 
 

 

Conclusions for 2-Methoxy-1,3-Dioxolane and Hydronium

   This surface showed that the proton transfer step was lower in energy than the separated molecules.  This means when the molecular complex is excited just high enough in energy to transfer the proton, it will not return to the separated state.  In other words this reaction will only go forward when the proton transfer is induced.   Since this PM3 calculation gave this great preliminary result, higher levels of theory were tried.  Calculations were done using ab initio methods, specifically Hartree-Fock.  In these calculations all of the orbital information is from solutions to the Schödinger equation.  This is more accurate than using semi-empirical information since the experimental values are from molecules have bonds not as strained as the ones in the molecules that are being studied.
    Unfortunately, just the acid proton on the methoxy of the dioxolane, the methoxy did not break off as a methanol.  This meant we could not say conclusively from the calculations that the rate-determining step was the proton transfer.  Another molecule had to found.
 
 

  Oxiranes were tried next.  The simplest one, the plain oxirane, was no better than the ortho esters.  It did not go on to do the rest of the chemistry after the proton transfer. In this case it was to open the C-C-O ring.  However, after adding the methyl and the methoxy groups the ring, the ring opened up with no problem once the proton was placed on the oxygen of the ring.  However, hydronium was too strong of an acid for this calculation. This complex did not optimize at the hydrogen bond, but at the open ring.  Another simple acid, ammonium, was used instead to build the PES.
   The PM3 PES was not very promising.  The energy of the transition state was higher than the energy of the separated molecules.  Since oxiranes are high strained molecules because of the three-membered ring, the ab initio calculations were then done.  The Hartree-Fock method and the 6-31G* basis set were used.  This basis set was chosen because it was the smallest one that gave reliable data.  STO-3G did not allow the ring to be broken up with just the acid proton and the oxirane.
 
 

   The PES calculated for 2-methoxy-2-methyl-oxirane and ammonium shows that the separated compounds are higher in energy than the transition state of the proton transfer.  In other words, reaction will only go forward if the molecule is excited just enough to transfer the proton.   When the proton is transferred to the oxirane, the ring opens up.  This shows that the reaction continues on after the proton transfer, which is what is expected and observed experimentally.
  The IRC, intrinsic reaction coordinate, calculations gives a better picture of what the real PES should look like because all of the configurations of the molecules will be calculated as the proton is moved toward the oxirane. This PES shows calculations that were made by only moving the proton toward the oxygen on the oxirane ring along one path.  The IRC showed that minimum for the hydrogen bonded complex in these first set of calculations is not a local minimum.