Methyl chloride calculations

The anomeric effect is also present in acyclic systems and stabilizes conformations that allow antiperiplanar (ap) alignment of the C—X bond with a lone-pair orbital of the heteroatom. Anomeric effects are prominent in determining the conformation of acetals and a-alkoxyamines, as well as a-haloethers. MO calculations (4-3IG) have found 4kcal/mol as the difference between the two conformations shown below for methoxy-methyl chloride. ... 

Levy (Chapter 6) has also explored the use of supercomputers to study detailed properties of biological macromolecule that are only Indirectly accessible to experiment, with particular emphasis on solvent effects and on the Interplay between computer simulations and experimental techniques such as NMR, X-ray structures, and vltratlonal spectra. The chapter by Jorgensen (Chapter 12) summarizes recent work on the kinetics of simple reactions In solutions. This kind of calculation provides examples of how simulations can address questions that are hard to address experimentally. For example Jorgensen s simulations predicted the existence of an Intermediate for the reaction of chloride Ion with methyl chloride In DMF which had not been anticipated experimentally, and they Indicate that the weaker solvation of the transition state as compared to reactants for this reaction In aqueous solution Is not due to a decrease In the number of hydrogen bonds, but rather due to a weakening of the hydrogen bonds. 

Create a bond inventory and estimate the energy change for each reaction. Based on the values that you calculate, which reaction is more suitable for industrial production of methyl chloride Explain. 

Wolfe and Kim s view of the origin of secondary a-deuterium KIEs has been challenged by two different groups. Barnes and Williams (1993) calculated the transition state structures and the secondary a-deuterium KIEs for the identity SN2 reactions between chloride ion and several substituted methyl chlorides (reaction (11)). 

The calculations were performed at the semiempirical level using AMI parametrization. The results for the methyl chloride reaction (Table 8) supported Williams earlier findings for the methylammonium ion-ammonia reaction (p. 147) and the results by Wolfe and Kim in that the inverse secondary a-deuterium KIE arose from an increase in the C —H stretching force constants which accompanied the change from sp3 hybridization at the a-carbon in the reactant to the spMike hybridization in the transition state. More important, however, were the observations that (i) the total KIE is dominated by the vibrational (ZPE) component of the KIE with which it correlates linearly, and (ii) that the inverse contribution from the C —H(D) stretching vibrations is almost constant for all the reactions. Ibis suggests that the contribution from the other vibrations, i.e. the rest in Table 8, determines the magnitude of the KIE. In fact, Barnes and Williams stated that the... 

Table 8 The AMI calculated semiclassical secondary a-deuterium KIEs, the stretching and other contribution to the KIEs and the C—Cl transition state bond lengths for the identity SN2 reactions between chloride ion and substituted methyl chlorides.0...

It used to be postulated that the magnitude of the alpha-carbon KIE in an Sn2 reaction is an indication of the transition state symmetry. The expectation was that this KIE reaches maximal value for a symmetric transition state and drops back to unity for extremely early or late transition states. That expected behavior is marked by the solid line in Fig. 10.10. However, recent calculations of the nucleophilic substitution of chloride from methyl chloride by a broad variety of nucleophiles... 

Fig. 10.10 Postulated (solid line) and calculated (points) a-carbon KIEs for the reaction between methyl chloride and various nucleophiles (Mattsen, O., et al. J. Org. Chem. 70, 4022 (2005))...

Example calculation Cl Cl substitution in methyl chloride. Here we will create an... 

Table 3. Measured (Black and Law 2001) and ab initio vibrational frequencies for methyl chloride, C CX.Ab initio frequencies are calculated with GAMESS, using the Hartree-Fock method and 6-31G(d) basis set. The ratio of each measured and model frequency is also shown.

Calculated CX stretching frequencies for these compounds (repeating the data in Appendix A7) are provided in Table 7-3 and compared to measured values. As expected, limiting (6-311+G basis set) Hartree-Fock frequencies are all larger than experimental values. In fact, with the sole exception of methyl chloride at the 3-2IG level, Hartree-Fock frequencies are always larger than experimental frequencies, irrespective of choice of basis set. 

We have examined the proton transfer reaction AH-B A -H+B in liquid methyl chloride, where the AH-B complex corresponds to phenol-amine. The intermolecular and the complex-solvent potentials have a Lennard-Jones and a Coulomb component as described in detail in the original papers. There have been other quantum studies of this system. Azzouz and Borgis performed two calculations one based on centroid theory and another on the Landau-Zener theory. The two methods gave similar results. Hammes-Schiffer and Tully used a mixed quantum-classical method and predicted a rate that is one order of magnitude larger and a kinetic isotope effect that is one order of magnitude smaller than the Azzouz-Borgis results. 

The reason is that ions are much more stable in water than in the gas phase for example, the transfer of a chloride ion from the gas to water is exothermic by —85 kcal. The AH° value for the corresponding transfer of a methyl cation, CH3 is not known with certainty, but is about —80 kcal. These ionic solvation energies are clearly large. In contrast, the AH° for solution of methyl chloride in water is small (about 1 kcal). We can use these data to calculate the heat of ionic dissociation of chloromethane in water ... 

Exercise 26-42 From appropriate p values (Table 26-7) and a- values (Table 26-6), calculate the rates of hydrolysis of 4-CH3-, 4-CH30, 4-N02-phenyl methyl chlorides relative to phenylmethyl chloride (a) in water at 30° in the presence of base, and (b) in 48% ethanol at 30°. Explain why there is a greater spread in the relative rates in (b) than in (a). 

Most of these theoretical investigations have been carried out using methyl compounds as the substrate. For example, the Sn2 reaction between OFT and methyl chloride has been investigated for non-linear and linear collisions using ab initio molecular dynamics calculations.105 The potential energy surface was calculated at the MP2/6-311-I— -G(2df,2pd) level of theory and the collision energy was set at 25 kcal mor1. The results for 495 trajectories indicated that the reactants pass from the initial encounter complex to the transition state in 0.02 ps and to the product encounter... 

B3LYP/6-311+- -G -level calculations have been used to predict the structure of the encounter complex (68) for the. S n2 reaction between F and methyl chloride in the presence of one molecule of water.106 Structure (68) was chosen as the encounter complex even though it does not have the lowest energy, but because it has the greatest negative charge on fluorine. Structure (69) is the encounter complex for the reverse reaction. 

The origin of the diastereoselective alkylation of enolates of oxazolopiperidones (2) and (3) has been studied by means of theoretical calculations and experimental (g) assays.18 For the unsubstituted oxazolopiperidone, the alkylation with methyl chloride is predicted to afford mainly the exa product, a finding further corroborated from the analysis of the experimental outcome obtained in the reaction of the racemic oxazolopiperidone. However, such a preference can be drastically altered by the presence of substituents attached to the fused ring. 

---