Sn1 And Sn2 Review.docx

LUMO-HOMO Gap 1) Electrons attack from HOMO (i.e. nucleophile) to LUMO (i.e. electrophile). 2) Best reactions involve the best electrophile and the best nucleophile as the electrons in HOMO can occupy an MO that is much lower in energy than the HOMO. 3) Having a LUMO lower in energy assist in creating that low-energy MO. 4) The best electrophile will have a low-energy LUMO; a low-energy LUMO is provided by an increase in electron withdrawal (i.e. by electron-withdrawing groups) and/or a decrease in electron donation (i.e. by electron donating groups) a) Increase in electron-withdrawal increases effective nuclear charge; increased effective nuclear charge increases energy-lowering attraction and decreases energy-increasing repulsion b) Decreases in electron-donation decreases effective nuclear charge; decreased effective nuclear charge increases energy-increasing repulsion and decreases energy-lowering attraction. 5) The best nucleophile will have a high-energy HOMO; a high-energy HOMO is provided by an increase in electron donation (i.e. by electron-donating groups) and/or a decrease in electron withdrawal (i.e. by electron withdrawal groups) a) Increase in electron-withdrawal increases effective nuclear charge; increased effective nuclear charge increases energy-lowering attraction and decreases energy-increasing repulsion b) Decreases in electron-donation decreases effective nuclear charge; decreased effective nuclear charge increases energy-increasing repulsion and decreases energy-lowering attraction. 6) Best nucleophile (HOMO) and best electrophile (LUMO) have similar energies or even better: will have the LUMO be at a lower energy than the HOMO to increase the energy released from putting the electrons from the nucleophile in lower orbitals Nucleophiles 1) SN2 reactions more sensitive due to nucleophile being in the RDS and thus influencing the rate of reaction more directly (i.e. kinetics) a) A higher HOMO (i.e. moderate, excellent) is favored for SN2 reactions. b) Higher sensitivity means that if presence of moderate, excellent nucleophiles, a higher chance of reaction being SN2 than SN1 with all other factors being equal. 2) RDS in SN1 reaction only involves the formation of the carbocation and has no contribution from the nucleophile used. a) Given that the electrophile in this case is a carbocation and carbocation are great electrophile (i.e. LUMO is lower in energy), then a weaker nucleophile (i.e. a lower HOMO) would suffice Aside: Nucleophiles, Bases 1) Basicity follows from base strength (i.e. recall that the stronger the base compared to another base, the weaker the conjugate acid of the former base than the conjugate acid of the later base) 2) Generally strong nucleophiles are molecules that have enhanced their diffusive nature of their atomic orbitals (i.e. having diffused orbitals starting from the principle quantum number of 2). a) Such enhancements serve to increase the energy of the HOMO and thereby increase nucleophilicity. b) Consider the hydroxide ion as an example in which the electron density is polarized onto the oxygen atom, already having diffused 2p, 2s orbitals (i.e. that hybridize to the appropriate hybrid orbitals); the greater electron density manifested in the negative charge provides reduces the effective nuclear charge, increasing the HOMO and thus nucleophilic strength. c) Many cases where nucleophilicity and basicity parallel each other according to this example. 3) Note the categories of nucleophilic/base strength: a) Strong nucleophile, strong base: parallelism between basicity and nucleophilicity followed; bases that have conjugate acids starting from pKa of 15 (i.e. water and above) will suffice i) Examples: anionic oxygen and nitrogen species b) Strong nucleophile, weak bases (i.e. exceptionally strong nucleophiles): deviates from parallelism; greater emphasize on polarizability (i.e. diffused nature of orbitals; increase diffusivity with increase atomic size) and resonance that results in decreased base strength i) Example: sulfur, phosphorous, halide anions c) Weak nucleophile, strong base: bulkiness of the nucleophile (i.e. a steric effect) affects kinetics of the reaction and thus increased bulkiness yields a slower reaction and reduced nucleophilicity; plus, reduction in the diffused nature of the atomic orbitals reduces nucleophilicity (e.g. hydride)

i) Bulky: LDA, tert-butyl base ii) Decreased polarizability via decreased diffusive nature of orbitals: hydride ion d) Weak nucleophiles, weak bases: bases with conjugate acids way below pKa of 15. i) Examples: neutral species with conjugate acids near negative pKa values Substrates, Electrophiles 1) SN1 reactions are more sensitive due to RDS- formation of carbocation yielding an electrophile and thus influencing the rate of reaction directly (i.e. kinetics) a) Higher sensitivity means that formation of the most stable carbocations (i.e. tertiary and resonancestabilized carbocations), a higher chance of reaction being SN1 and SN2. 2) RDS in SN2 does not deal with an electrophile directly but instead the substrate, thus making SN2 reaction less sensitive to electrophile compared to SN1. Leaving Group 1) SN1 reactions are more sensitive to the nature of the leaving group given that leaving group leaving is necessary in the formation of the carbocation (i.e. the RDS). a) An excellent LG reduces the energy of activation because the bond of a good LG to the remaining structure is weakened (i.e. longer bond) and thus contributes to the energy of the reactant being higher in energy; reactants being higher in energy reduces the activation energy. 2) SN2 reactions can do fine with any good leaving group because the leaving group also depends on the nucleophile entering the LUMO of the leaving group bond. (i.e. much collaboration, synergy in the leaving group leaving rather than that in SN1) Solvent 1) BOTH SN1 and SN2 need a polar solvent otherwise charged species created, present in both cannot dissolve into solution; no dissolution results in precipitation of the charged species, rendering them useless in completing either reaction a) SN1 requires polar solvent to mainly solubilize carbocation in RDS (i.e. secondarily to solubilize the nucleophile in subsequent reaction) b) SN2 requires polar solvent to mainly solubilize the nucleophile in the RDS 2) BOTH SN1 and SN2 are sensitive to solvent but perhaps SN2 reactions more sensitive than SN1 in type of polar solvent: a) Recall that SN1 reactions proceed irrespective of the nucleophile due to the RDS being the formation of the carbocation; carbocations are excellent electrophiles and so could weakened nucleophile at the minimum to perform SN1 reaction i) Effect: generally, does not matter whether polar solvent is aprotic or protic because the effect of either protic or aprotic comes after the carbocation is formed rather than before. b) Recall that SN2 reactions depend on the type of nucleophile used being that the nucleophile is involved in the RDS; solvent should maintain/enhance nucleophilicity of a nucleophile i) Protic solvents attenuate nucleophilicity of a nucleophile by engaging the nucleophile in hydrogen bonding, resulting in a solvent shell (1) Solvent shell must be removed in order for nucleophile to react and thus further energy is required for the SN2 reaction ii) Aprotic solvents do not result in the formation of solvent shell and thus is preferred for SN2.