Solvent Effects and SN2 and SN1 reactions: Nucleophilic Substitution | Chemistry Net

Solvent Effects and SN2 and SN1 reactions: Nucleophilic Substitution



SN2 reactions and solvent effects



Polar aprotic solvents – solvents that do not have acidic proton such as DMSO, DMF, CH3CN, HMPA - accelerate the rate of  SN2 reactions by solvating the cation thus making the nucleophile more available to react.

On the contrary, protic solvents such as alcohols or amines decrease the rate of SN2 reactions since they tend to solvate nucleophiles (Fig. 1). The partial positive charge that exists in the O-H hydrogens solvate the negative charge of the nucleophile (Nu:-). Solvated nucleophiles are held tightly and  are unable to react with the electrophilic substrates – compounds that have leaving group.

Fig. 1: Partially positively charged hydrogens from polar O-H bonds solvate partially negative charge of the nucleophile. Solvated nucleophiles – as the one shown above – are unable to react with electrophilic substrates.

Fig. 1: Partially positively charged hydrogens from polar O-H bonds solvate partially negative charge of the nucleophile. Solvated nucleophiles – as the one shown above – are unable to react with electrophilic substrates.

The effect of solvents on the rate of SN2 nucleophilic substitution reactions is shown in Fig. 2.
Fig. 2: Solvents and SN2 reactions rates.

Fig. 2: Solvents and SN2 reactions rates.

The same electrophile -  especially compounds having a leaving group in a secondary carbon – can react under SN2 or SN1 conditions by simply changing the solvent and the nucleophile. Under SN2 conditions and when a chiral carbon exists an inversion is observed in the product while under SN1 conditions a racemic mixture is produced (Fig. 3).
 
Fig. 3: The secondary substrate shown above reacts with CN- - a strong nucleophile - in a polar aprotic solvent acetone under  SN2 conditions giving an inverted product at the secondary carbon. The same substrate reacts with OH- - a weak nucleophile – in a polar protic solvent like methanol under SN1 conditions giving a racemic mixture

Fig. 3: The secondary substrate shown above reacts with CN- - a strong nucleophile - in a polar aprotic solvent acetone under  SN2 conditions giving an inverted product at the secondary carbon. The same substrate reacts with OH- - a weak nucleophile – in a polar protic solvent like methanol under SN1 conditions giving a racemic mixture.
SN1 reactions and solvent effects

SN1 reactions proceed more rapidly with more stable carbocations, therefore the rate of reactivity is correlated to carbocation stability. Polar protic solvents, such as water and alcohols, organic acids and inorganic acids (H2SO4, H3PO4), stabilize the transition state by solvating the carbocation intermediate and therefore increase the reaction rate even more.
In general, polar protic solvents are able to solvate both cations and anions through hydrogen bonds. For example they dissolve salts such as NaBr by hydrogen bonding to the anion Br- and electron donation to the cation Na+.
By choosing a polar protic solvent such as methanol, the substrate shown in Fig. 4 gives a racemic mixture reacting under SN1 conditions. The intermediate in the reaction is a carbocation that rearranges to form a tertiary carbocation before reacting with methanol.
The same substrate when it reacts with methoxide CH3O- in the presence of acetone – an aprotic solvent – gives a single product with inversion at the carbon atom having the Br group.
Fig. 4: The secondary substrate shown above reacts with CH3OH - a protic solvent and weak nucleophile – in an SN1 fashion to produce two products – a racemic mixture. The same substrate in the presence of methoxide in acetone – an aprotic solvent – reacts in an SN2 fashion to give a single product with inversion at the C atom attached to the Br.

Fig. 4: The secondary substrate shown above reacts with CH3OH - a protic solvent and weak nucleophile – in an SN1 fashion to produce two products – a racemic mixture. The same substrate in the presence of methoxide in acetone – an aprotic solvent – reacts in an SN2 fashion to give a single product with inversion at the C atom attached to the Br.

References

1. L. Sun et al., J.A.C.S., 123, 5753 (2001)
2. R. Bruckner, “Advanced Organic Chemistry – Reaction Mechanisms”, 2nd Edition, Elsevier, 2002
3. M.B. Smith & J. March “March’s Advanced Organic Chemistry”, 6th Edition, Wiley-Interscience, 2007
4. P. Muller, J. Mareda in G.A. Olah “Cage Hydrocarbons”, Wiley, 1990

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