Frontside reaction

One after the other, step through (or animate) the sequence of structures depicting the SN2 and proton transfer reactions shown above. Compare the two. From what direction does cyanide approach the hydrogen in HCl From the same side as Cl ( frontside ), or from the other side ( backside ) Does the Sn2 reaction follow a similar trajectory ... 

When X and Y are identical halogen atoms, the potential surface for this reaction is represented by a well for the frontside ion-dipole complex [X CHaY] , a TS for the [X CH3 Y] stmcture in which the methyl moiety is planar, and a backside ion-dipole complex [XCH3 Y] that leads to products. These... 

Scheme 6.14 Backside and frontside substitution reactions of methyl radical with disilane...

Problem 7.20 Optically pure (S)-(-i-)-CH3CHBr-n-CjH,3 has [a] = -1-36.0°. A partially racemized sample having a specific rotation of -i-30° is reacted with dilute NaOH to form (R)-(-)-CH,CH(OH)-n-CsH,3 ([ ] =-5. 97°), whose specific rotation is -10.3° when optically pure, (a) Write an equation for the reaction using projection formulas, (b) Calculate the percent optical purity of reactant and product, (c) Calculate percentages of racemization and inversion, (d) Calculate percentages of frontside and backside attack, (e) Draw a conclusion concerning the reactions of 2° alkyl halides. (/) What change in conditions would increase inversion ... 

Contrary to the case of anionic reactions, the formation of a strong proton-bound dimer for alcohols suggests that nucleophilic displacement may actually involve a frontside attack. Recent experiments carried out at atmospheric pressure by Speranza and Angelini (1980) using radiolytic techniques with isolation and glc analysis of neutral products reveal some interesting stereochemistry. For example, the reaction of protonated epoxy-rra/is-but-2-ene with H20 results in 98% inversion of configuration, while a similar reaction with cis-1 -chloro-4-methylcyclohexane results in approximately 80% of tro/is-4-methylcyclohexanol. With the high pressures utilized and with the possible participation of cluster ions a likelihood in this case, the data are consistent with a Walden inversion for these cases. 

Further support for the idea that cationic nucleophilic displacement occurs with inversion of configuration has been advanced by Hall et al. (1981). The study of reaction (55) in an electron-bombardment flow reactor at reagent pressures below 10 3torr, followed by neutral product analysis (Marinelli and Morton, 1978), reveals that these reactions also occur via backside attack. This is in disagreement with the original suggestion of Beauchamp et al. (1974) who proposed a frontside displacement in the case of t-butyl alcohol. 

Because of the cage structure of the above bicyclic systems, only frontside attack at silicon is possible. Thus an increase of the reaction rate would be observed for the Si—X bonds that have a high degree of s character. Our analysis is as follows ... 

Their approach in looking into the problem further was to find structures in which specific covalent bonding to the back side of the carbon undergoing substitution is difficult or impossible. As models for reactions at tertiary carbon they chose bridgehead substitutions. We have seen in Section 5.2 that rates in these systems are retarded, in some cases by many powers of ten, because of the increase in strain upon ionization. But the important point in the present context is that it is impossible for a solvent molecule to approach from the back side of a bridgehead carbon the only possibilities are frontside attack, known to be strongly disfavored (Section 4.2), or limiting SW1 solvolysis with nonspecific solvation. 

Figure 10.14 Frontside attack of a nucleophile, symbolized by N, on a C—X bond. Symmetry prevents HOMO-LUMO interaction the only interaction is between filled levels. The reaction will not take this path.

Another application is to bimolecular SN2 and S 2 substitutions. Recall from Chapter 4 (pp. 174 and 205) that the nucleophilic reaction prefers backside attack by nucleophile on substrate whereas the electrophilic reaction prefers frontside attack. Figure 10.14 shows the appropriate frontier orbitals for frontside attack by a nucleophile. The nucleophile, symbolized by N, is the donor, and the C—X bond is the acceptor. The symmetries of the nucleophile HOMO and the C—X LUMO do not match (13) therefore only the filled-filled HOMO-... 

The kinetics of the nucleophilic substitution reactions of benzoic anhydrides with anilines in acetonitrile-water have been studied.74 A frontside 5 k2 mechanism with a four-membered ring transition state has been proposed. 

Lee s group has published extensive results on aminolysis of sulfonates.278 281 Thus the reactions of anilines witii 2-cyano-2-propyl and 1-cyanocyclooctylarenesulfonates in acetonidile have been stiidied.278 A dissociative, S k2 mechanism with a loose TS is supported from die usual LFERs. An 5k2 mechanism is also found for the reaction in acetone of (Z)-benzyl (X)-benzenesulfonates witii (Y)-pyridines.279 Nucleophilic substiditions witii die cycloalkyhnetiiylsulfonates (306) and anilines in MeOH were also sfridied.280 Finally die reaction of tiiiopheneethyl arenesulfonates (307) with anilines and AvA -dimethylanilines in MeCN has been reported on.281 Frontside-atiack in an 5n2 mechanism witii a four-centre TS is supported. 

HO-OH2+.14 This reaction forms two water molecules and a carbenium ion, which is then hydrated to form the protonated alcohol. The degenerate gas-phase reactions between HF and protonated alkyl fluorides RFH+ (R = Me, Et, i-Pr, r-Bu) were investigated by ab initio methods.15 With the exception of MeFFi+, the protonated alkyl fluorides can be viewed as weak complexes of the carbocation R+ and FiF. Both frontside and backside substitutions occur, supporting the proposal (see Introduction)8 that nucleophilic substitution reactions are better understood through such a competition as opposed to the traditional S /S 2 competition. 

The. S n reactions between HF and protonated methyl, ethyl, isopropyl, and /-butyl fluorides in the gas phase have been examined at the MP2/6-31+- -G(d,p) level of theory.112 113 The reaction of CH3FH+ clearly occurs via back-side attack as the transition state for this process is of lower energy than the transition state for frontside attack. The EtFH+ can react via a more stable back-side. S N2 reaction or an. S n 1 reaction via front-side attack since the. S N 1 pathway is 4.4 kJmol-1 lower in energy. No. S n2 path could be found for i-PrFH+ and the front- and back-side pathways had equal activation energies for /-BuFH+, which effectively reacts by an. S N1 mechanism. The conclusion is that the preference for back-side attack is reduced as the size of... 

The transition structures for the hydrolysis reactions of methyl, /-butyl, and ada-mantyl chlorides in the gas phase and in water were calculated using the B3LYP/6-31-G(d) level of theory and the PCM solvation model.82 In the gas phase, backside attack is strongly favoured for the methyl chloride reaction and slightly favoured for the t -butyl chloride reaction. Frontside attack is favoured for the adamantyl chloride... 

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