Why Are Halide Ions Replaced by Weaker Nucleophiles in Substitution Reactions?

[mycotheology]

I'm trying to get a good understanding of why one nucleophile, replaces another nucleophile during a nuclephilic substitution. For instance, halide ions are strong nucleophiles so why are they so easy to replace, even by weak nucleophiles like OH^-? I read that a way to estimate the strength of a leaving group, you look at the its pKa when attached to a hydrogen atom. The lower the pKa, the better the leaving group. With the exception of HF, all the hydrohalic acids are very strong which explains why they make good leaving groups. I read that tosylate groups are as good as halide groups for leaving so I'm guessing tosylic acid has a pretty low pKa. So is it mainly the strength of the leaving group that underlies nucleophilic substitutions?

Do nitro groups participate in nucleophilic substitution? Their corresponding acid is nitrous acid which is pretty strong.

 

[DrDu]

In some way, it is all a question of thermodynamics, especially of the mass action law. Typically, the concentration of OH- is high but there are no Cl- ions in the pot, so substitution of Cl by OH is favored entropically.

 

[chemisttree]

... and OH^- is a LOUSY leaving group even after the reaction has proceeded somewhat and chloride anions begin to have a measurable concentration.

In general, the stability of the leaving group affects the rate of reaction with the more stable species undergoing more rapid reaction. Also, the more basic the leaving group is the slower the reaction will proceed.

 

[DrDu]

True, but this stability of the leaving group in solution is also a thermodynamic concept.

 

[LudusRex]

I can provide some insight into the concept of nucleophilic substitutions and the factors that influence the replacement of one nucleophile by another. Nucleophilic substitution reactions involve the attack of a nucleophile on an electrophilic center, resulting in the displacement of a leaving group. The strength of the leaving group is indeed a key factor in determining the ease of substitution, as a weaker leaving group is more easily displaced by a nucleophile.

In the case of halide ions, they are strong nucleophiles due to their high electronegativity and large size, which allows them to easily donate their lone pair of electrons. However, their corresponding acids (hydrohalic acids) have low pKa values, indicating that they are strong acids and therefore good leaving groups. This makes them vulnerable to being replaced by other nucleophiles, even weaker ones like OH-. The same concept applies to tosylate groups, which have a low pKa and therefore make good leaving groups.

It is important to note that the strength of the nucleophile also plays a role in nucleophilic substitution reactions. A stronger nucleophile will be more likely to successfully attack the electrophilic center and displace the leaving group. This is why certain nucleophiles, such as hydroxide (OH-) and tosylate (TsO-), are able to replace halide ions in nucleophilic substitutions.

In regards to nitro groups, they can participate in nucleophilic substitution reactions, but their corresponding acid (nitrous acid) is not as strong as hydrohalic acids or tosylic acid. This means that nitro groups may not be as easily replaced as halide ions or tosylate groups in nucleophilic substitutions.

Overall, the strength of the leaving group is a key factor in nucleophilic substitutions, but the strength of the nucleophile also plays a role. It is important to consider both factors when predicting and understanding nucleophilic substitution reactions.