60th Annual Report on Research 2015

A. Specific Aims

The aims in the original application have not been modified.  Our goal is to determine the role of thermally-activated heavy-atom tunneling in the cycloaromatization reactions of hydrocarbons yielding diradicals, namely (1) a,3-didehydrotoluene, (2) fulvenyl diradical, and (3) 1,5-didehydroindene. Thus far, we have obtained quantitatively and qualitatively accurate descriptions of the cycloaromatization of (1). We have developed theoretical methodology including computer code to provide accurate vibrationally adiabatic ground-state curves for the formation of a,3-didehydrotoluene and to determine the magnitude of thermally activated heavy-atom tunneling. Progress has been been made toward determining of the contribution of tunneling in cycloaromatizations leading to (2) fulvenyl diradical and (3) 1,5-didehydroindene.

B. Studies and Results

A substantial fraction of the objectives in Aims #1, #2 and #3 were met in the first year of the grant.  The innovative potential of the project remains the same as was stated in the original application.  We have computed and can accurately reproduce experimentally-derived thermochemical data for the cycloaromatization yielding a,3-didehydrotoluene. Our methodology enables the determination of the vibrationally adiabatic ground-state curves (aka, VaG) where the tunneling probability is the highest. For the formation of a,3-didehydrotoluene, the highest tunneling probability is 2 kcal/mol below the top of the VaG curve. Furthermore, the kinetic isotope effects (KIE) were computed by comparing rates of two isotopomers; firstly by means of mass increase at a carbon directly involved the reaction, and secondly with the mass increase at a carbon remote to the reaction site. The tunneling probability depends inversely on the particle mass, thus substituting ¹²C by ¹³C reduces the tunneling. Tunneling has a significant effect on the KIE. The 1.35 increase of KIE at 312 K and slopes of the KIE curves were larger when tunneling is included in calculations by means of small curvature tunneling approximation. We estimated that thermally activated tunneling increases the rate at 312 K by the factor of 1.7. In collaboration with Dr. Charles Doubleday (Columbia University) a manuscript is in preparation on contribution of carbon atom tunneling on cycloaromatization leading to a,3-didehydrotoluene to be submitted for publication about March 2016. Fortunately, I have also had the opportunity to collaborate on other physical-organic chemistry topics by adding computational data and insight.

Since the beginning of the ACS PRF UR4 grant, three papers have been published on other computational projects and topics.  One of the papers has appeared in the Journal of Organic Chemistry that described the detection of an oxygen-atom photoexchange process of N-nitrosamines, which may provide a clue to new factors significant in nitrosamine phototoxicity (Figure 1).

Figure 1.

The second paper was published Tetrahedron Letters described a unique oxidative ring-contraction of 3H-1-benzazepines to quinoline derivatives (Figure 2). 

Figure 2.

A third manuscript has appeared in in the Journal of Physical Organic Chemistry that described the Bergman cyclization of an enediyne fused to a butylated hydroxytoluene (di)radical scavenger (Figure 3).  This computed reaction was unique in not only reaching diradial intermediate but also a quinone methide intermediate.

Figure 3.

We are also preparing a review manuscript for a book chapter entitled “Brief Review of Available Computational Methods” in the book “Applied Theoretical Organic Chemistry” (D. Tantillo, ed.), and a review manuscript for Tetrahedron Reports summarizing cases of tunneling contributions to the reaction rates above cryogenic temperatures. In summary, the above papers published and in preparation describe tunneling, chemistry of reactive intermediates including diradicals and peroxy nitrosamines.

 C. Significance

Years 1 has resulted in proof-of-concept data for our project on thermally activated tunneling in reactions. Thermally-activated heavy-atom tunneling is relatively underappreciated among organic chemists because at higher temperatures tunneling mixes with classical rates and can be difficult to decipher. The influence of heavy-atom tunneling on reaction rates is emerging as more relevant than previously thought. Thus, there is a need to quantify this effect for better understanding of chemical reactivity.

In addition to the impact on fundamental understanding of chemical reactivity and C-C bond formation, this research grant has had a significant effect on my career. Importantly, the PRF grant support has allowed my research group to collect critical data used in the presentations of an invited talk entitled Mechanistic Studies of Diradicals and Oxygen Exchange Processes at the Gordon Research Conference (GRC) on Physical Organic Chemistry in Holderness, New Hampshire on June 24, 2015. In addition, I was delighted to give an invited talk entitled The Discovery of the Bergman Cyclization Reaction and How It Impacted My Research Direction and Career and to chair a session honoring Professor Robert Bergman at the 35^th Reaction Mechanisms Conference (RMC) at the University of California ¾ Davis on June 23, 2014.

Furthermore, this research grant has had a significant impact on students in my group at Baruch College. It has provided my students with the opportunity to carry out computational research and collect results that earned them the first and the second prize at the 17^th and the 18^th Annual Undergraduate Research Symposium in the Chemical and Biological Sciences, University of Maryland, Baltimore County (UMBC) in 2014 and 2015. Two students had delivered oral presentations at the 250^th American Chemical Society National Meeting & Exposition, Boston, August 16-20, 2015. Additionally, two students had given oral presentations at the 63^rd Annual Undergraduate Research Symposium of the American Chemical Society at Queensborough Community College, on May 9, 2015. In summary, seven students have participated in the research project outlined in the grant thus far. One of the students, Anastasiya Badziai, was recently accepted to dental school at the University of Connecticut. Student, Kitae Kwon and Jade Marino Creto (currently in Brazil), have been in process of preparing to apply to Ph.D. programs in chemistry.

D.  Plans

We will continue to address the Specific Aims in the next year of support, and will utilize our developed methodology to address contributions of tunneling in cycloaromatization reactions leading to fulvenyl diradical, and 1,5-didehydroindene.