theoretical data modelled the experimental data. Using the solver function in Excel to solve for the values of the constants k1-k12 in the theoretical model, the best fit obtained was plotted and is shown in Figure 39. The theoretical data appears to model the consumption of MVK (2a; A), 2,2‟-dithiodibenzaldehyde (201, D) and the formation of 4-hydroxythiochroman (217a; I) quite closely, but the theoretical data for the thiochromene (202a; J) deviates from the experimental data. Given the complexity of this reaction, such deviations are not surprising. It may be that the proposed model is not sufficiently comprehensive, but the fact that three of the four theoretical curves model the data reasonably well, suggests that the proposed model has some validity. The theoretical model does not take into account solvent effects which, in reality, may play a significant role on the mechanism. Moreover, while we have identified twelve possible steps for this reaction, it is possible that there could be more.
These limitations in our theoretical model may have contributed to the observed deviations, and have, at this stage, precluded determination of the overall rate law for the reaction. Table 2, however details the values of the rate constants (k1-k12) used to obtain the theoretical graphs in Figure 39.
Table 2. Values of the rate constants k1-k12 for the best fit shown in Figure 39.
Rate constant Value
k1
k2
k3
k4
k5
k6
k7
k8
k9
k10
k11
k12
0.0146 mol-1Ls-1 0.0196 mol-1Ls-1 1.6 mol-1Ls-1 0.04 mol-1Ls-1 0.00004 s-1 0.001 s-1 0.0003 s-1 0.0099 mol-1Ls-1 0.5 mol-1Ls-1 0.006 s-1
0.0000 mol-1Ls-1 0.07 mol-1Ls-1
Results and Discussion
76
0 0.05 0.1 0.15 0.2 0.25 0.3
-1000 1000 3000 5000 7000 9000 11000 13000 15000
Concentration mol/L-
mol/L-Time (s) MBH reaction of 2,2'-dithiodibenzaldehyde with MVK:
Concentration of reactants and products with time
A D I J
[CHO] [MVK] [OHPr1] [ThioC]
Figure 39. Concentration vs time graphs of the experimental (coloured symbols) and theoretical (solid lines) data; 2,2‟-dithiodibenzaldehyde 201 ( D; CHO) (red), MVK 2a (A) (green), 4-hydroxythiochroman 217a (I; OHPr1) (pink) and the thiochromene 202a (J;
ThioC) (blue).
2.1.5 Theoretical study of the MBH synthesis of 2H-1-benzothiopyrans
Theoretical studies were carried out based on the proposed mechanism6 and on the sequence of steps outlined in Schemes 57 and 58. Geometry optimisation of the proposed intermediates and products was carried out using the Gaussian 03 programme. In some cases, conformational searches were carried out using the VEGA ZZ 2.4.0 programme143 before optimisation with Gaussian. The hybrid density functional B3LYP with the 6-31G(d) basis set were used for the calculations. B3LYP combines exchange (Becke-3-Parameter)144 and correlation functionals (Lee, Yang and Parr)145 in computational results, and has been used widely in theoretical work involving the determination of reaction mechanisms giving results with acceptable levels of accuracy. The proposed mechanism6 (Scheme 50), presumes that cleavage of the disulfide occurs after the MBH reaction − a presumption supported by the experimental kinetic data. Since theoretical mechanistic studies of the MBH reaction have received considerable attention in recent years (see Section 1.1.1.2),40,41,42,44
the present study has focussed mainly on the post-MBH mechanistic sequences. Nonetheless, some attention
Results and Discussion
77 was given to exploring the structures of the initial DBU- and Ph3P-MVK zwitterions. In earlier theoretical work by Lobb and Kaye,146 it was found that the zwitterion formed in the inital step of the MBH reaction, between the catalyst and activated alkene (see Scheme 57: A + B-> C), failed to afford a minimised geometry. In their case, DABCO was being used as the catalyst and MVK as the activated alkene, and an energy surface scan showed that attempts to decrease the distance between the DABCO nitrogen and the MVK vinylic carbon to form the N-C bond in the zwitterions, resulted in an increase in energy causing the system to fall apart – in spite of the fact that a transition state could be located and optimised.
Against this background, we sought to explore similar systems using DBU and Ph3P as catalysts, and 2,2‟-dithiodibenzaldehyde 201 and MVK as substrates. Energy surface scans of the N-C bond length and the torsion about this bond in both cis- and trans-configurations of the DBU and Ph3P-derived zwitterionic enolates were carried out. The results obtained were similar to those observed by Lobb and Kaye,146 with the trans-enolates at lower energies than the cis-enolates, a result that can be attributed to decreased steric crowding about the C=C bond in the former. Figure 40 illustrates the energy surface scan for the cis-enolate of the DBU-MVK zwitterion, while Figure 41 shows the results for the corresponding trans-enolate. The points marked a-d on the scan grid of the cis-DBU-MVK zwitterion (Figure 40), reveals an interesting pattern. Structure a shows the zwitterion during the first step of the scan, corresponding to point a; the N-C bond is intact with the system at a high energy.
Structure b, corresponding to point b, shows an interesting feature: hydrogen-bonding interactions have developed between the electronegative oxygen and one of the protons on the carbon next to the reacting nitrogen in DBU, leading to the formation of a six-centered complex, which is at much lower energy than the initial structure a. Structure b was optimised at the B3LYP level to establish if it was a stable structure. The results showed it to be stable, optimising to a minimum without falling apart. Point c, corresponds to the zwitterionic system (Structure c) with the highest energy. However, while the desired enolate moiety is evident in the structure, the N-C bond has lengthened instead of shortening.
Structure d exhibits the lowest energy attained for this system, but it is quite evident that the N-C separation has increased even further to 3.02Å, and the system simply disintegrates into the starting materials DBU and MVK. The trans-DBU-MVK zwitterion scan grid (Figure 41) on the other hand, failed to reveal any significant discontinuities, as observed with the cis-zwitterion. The zwitterion simply disintegrates to the reactants, DBU and MVK, at the lowest energy (Structure f). Structure e shows the structure of the zwitterion during the initial stages of the scan.
Results and Discussion
78 Figure 40. Energy surface scan grid for the cis-DBU-MVK zwitterion.
Figure 41. Energy surface scan grid for the trans-DBU-MVK zwitterion.
Structure a
Results and Discussion
79