Theoretical study of solvent and substituent effects on the Diels-Alder reactions
Mehdi Irani 1, Mohammad Haghgu, Mohammad Reza Gholami.
Department of Chemistry, Sharif University of Technology, AzadiAve.,Tehran, Iran P.O.BOX 11365-9516. [email protected]
Introduction
The Diels-Alder (DA) reactions are important in forming carbon- carbon (C-C) bonds for organic chemists. These types of reactions can proceed in gas or solution phases. The DA reactions are concerted and do not involve prominent charge distribution in transition state. Therefore solvent effects on these reactions must be negligible, but these reactions are dramatically accelerated in water solvent. These effects can be recognized by frontier molecular orbital (FMO) theory. In this work we studied solvent and substitute effects on two series of reactions. The first one is the reactions of 1,4-Benzoquinone with 2-methyl- 5-isopropylcyclohexa-1,3-diene (Reaction
1) and 1-methyl-4-isopropylcyclohexa-1,3-diene (Reaction 2). The experimental results show that the rates of these reactions in water are more than THF [1].
The second series of reactions is the reactions of 1,4-Benzoquinone with cyclopentadiene (Reaction 3), methylcyclopentadiene (Reaction 4) and 1,2,3,4,5- pentamethylcyclopentadiene (Reaction 5). Experimental results show that the relative rate constants in water solvent increase in the order of Reaction 5 > 4 > 3(in other word with adding of donating groups) [2].
Computational Details
Optimized geometries of the stationary points on the potential energy surfaces were performed using Beck’s three parameter hybrid exchange functional with the correlation functional of Lee, Yang and Parr (B3LYP) with 6-31G* basis set. Vibrational frequencies for the points along the reactions paths were determined to provide an estimation of the zero point vibrational energies (ZPVEs). The electron transfer between dienes and dienophile at the transition state were studied using the total Natural Population Analysis (NPA). To investigate solvent effects, calculations of reaction field
were carried out with the Onsager reaction field model. Furthermore, to investigate hydrogen bonding effects, the transition states (TSs) and 1,4-Benzoquinone were optimized by considering two water molecules near the hydrogen bonding sites (oxygen atoms). In order to investigate the hydrophobic effect on the reaction rates, we used a two- layered ONIOM method. In this method we have considered the average length of the forming C-C bonds as the reaction coordinate (RC).The geometry of reactants (at RC=7 Å) and TSs were optimized with ONIOM (B3LYP/6-31G*: UFF) method. The B3LYP/6- 31G* level of theory was applied to the reacting system and the rest of the system, containing 443 water molecules, were treated with the universal force field (UFF). The variation of the solute’s solvent accessible surface area (SASA) along the reaction coordinate was then calculated with TINKER version 4.2 molecular modeling package.
The SASA of the optimized structures of the reactants and TSs (the structures that optimized with ONIOM method) were calculated with a probe radius of 1.4 Å-2 corresponding to a water molecule. To calculate hydrophobic energy we used the fact that the change in SASA and free energy of hydration (∆GH) for hydrocarbon systems show a linear correlation with proportionality constant of about 0.01 kcal.mol-1.Å-2 [3].
Result and discussion
Tables 1 & 2 show FMO energy gap between diene and dienophile (EN) and relative rate constant (k) by various calculations. Calculated FMO energy gaps imply that the rate of the reactions increases by the closing of substituents to the reacting carbons (Reaction 2 in comparison to the Reaction 1) and adding of electron donating groups to the diene (Reaction 3, 4 & 5). However, the calculated k contradicts the FMO calculations.
Differences in the reaction rates can be interpreted by the steric effect in TSs. The steric effect in TS2 is more than TS1 and therefore the rate of Reaction 1 is higher than Reaction 2. In the second series of reactions both FMO energy gap and steric effect are important.
Onsager model could not predict the accurate sequence of reaction rates in water media.
This discrepancy is due to the insufficient using of nonspecific interactions which implemented in this model. Thus, specific solute-solvent interactions, such as hydrogen bonding and hydrophobic effect must also be considered. The relative rate constants which are calculated by considering hydrogen bonding effect show that stability of TSs increases with the addition of electron-donating groups. This is in agreement with the experimental results. It can be inferred that the dramatic acceleration in rate of DA reactions in aqueous solution arise from the hydrogen
bonding of this solvent with active sites of reacting molecules. The relative rate constants which are calculated by considering hydrophobic effect show that rate enhancements in water arise in part from hydrophobic association of the reactants but predominantly arise in part from enhanced hydrogen bonding between water molecules and the polarized transition state.
Fig 2 shows the total NPA charge of the dienophile moiety in TSs (QNPA)and the average of NPA charge on the oxygen atoms (QO) for all of reactions in various solvents.
According to the Fig 2 the electron transfer from the dienes to the dienophile at the TSs increases with adding of electron donating groups, closing of substituents to the reacting carbons and increasing of solvent's dielectric constant. It is obvious that, the hydrogen bonding is sensitive to small charge shift and its strength enhances considerably with this factor [3]. The strength of hydrogen bonding is related to its distance.
Table 1. FMO energy gap between diene and dienophile (EN) and relative rate constant (k) by various calculations for Reaction 1 and 2 in B3LYP/6-31G* level of theory
solvent Reaction 1 2 Gas phase Non Relative k 1 0.0007
Non EN(ev) 1.91 1.70 Onsager model H2O Relative k 1 0.00082
THF Relative k 1 0.0008
Table 2. FMO energy gap between diene and dienophile (EN) and relative rate constant (k) by various calculations for Reaction 3, 4 & 5 in B3LYP/6-31G* level of theory
solvent Reaction 3 4 5 Gas phase Non Relative k 1 3 2.8
Non EN(ev) 2.22 1.97 1.51 Onsager model H2O Relative k 1 4.06 3.01 THF Relative k 1 3.73 3.01 Hydrogen bonding H2O Relative k 1.00 4.38 90.93 Hydrophobic effect H2O Relative k 1.00 1.22 1.77
Reaction 3 Reaction 4 Reaction 5
-0.22
-0.32
gas THF H2O
SOLVENT Reaction 1 Reaction 2
-0.22
-0.3
SOLVENT
gas THF H2O
QNPA QNPA
(a) (b)
-0.52
-0.58
(c) (d)
Figure 1. The changing of (a) QNPA for reaction 1 and 2 (b) QNPA for reaction 3, 4 and 5 (c) QO for reaction 1 and 2 (d) QO for reaction 3, 4 and 5 in various phases.
References:
1. T. Sunakawa and C. Kuroda, Molecules., 2005, 10, 244.
2. E.S. Gawalt and M. Mrksich, J. Am. Chem. Soc., 2004, 126, 15613.
3. J. Chandrasekhar, S. Shariffskul and W.L. Jorgensen. J. Phys.
Chem. B., 2002, 106, 8078.
Reaction 1 Reaction 2
-0.55
-0.57
gas THF H2O
SOLVENT
<QO>
Reaction 3 Reaction 4 Reaction 5
<QO>
gas THF
SOLVENT H2O
