Rank the following carboxylic scid derivatives in order from LEAST to MOST reactive when they undergo nucleophilic acyl substitution reactions. If two are equal or close, you can use "=". Justify your answer in words - using leaving group ability, base strength, conjugate acid strength, pKa values, etc., if applicable. ### Reactivity of Carboxylic Acid Derivatives#### a. Rank the following carboxylic acid derivatives in order from LEAST reactive to MOST reactive when they undergo nucleophilic acyl substitution reactions. If two are close or equal in reactivity, please change the “<” to an “~” sign in your ranking.The structures provided are:- **A:** An amide group (NH₂)- **B:** An acid chloride group (Cl)- **C:** A hydroxyl group (OH)- **D:** An anhydride group (two carbonyl groups connected by an oxygen)- **E:** An ester group (single oxygen between carbon chains)Ranking: \[ A \quad \text{<} \quad B \quad \text{<} \quad C \quad \text{<} \quad D \quad \text{<} \quad E \]#### b. Justify your answer thoroughly in words. Your explanation should include, if applicable, leaving group ability, base strength, conjugate acid strengths, pKa values, etc.*Please write a comprehensive justification for the ranking, addressing factors such as the leaving group ability (how easily the group departs), the relative acidity of the hydrogen attached to the leaving group, the strength of the corresponding base of the leaving group, and relevant pKa values. Consider how these factors influence the reactivity of each carboxylic acid derivative.*

Nucleophilic acyl substitution reaction are defined as the class of substitution reaction that involves nucleophiles and acyl compund. This reaction takes place in two steps: 1) attack of carbonyl carbon atom of an acyl derivative by a nucleophile yeilds a tetrahedral intermediate. 2) The tetrahedral intermediate then eject the leaving group. The order of reactivity of carboxylic acid derivatives towards nucleophilic acyl substitution reaction is as follows: A < C < E < D < B Pka value of amide is 36 and of acyl halide is -7. The reactivity of carboxylic acid derivatives depends on two factors: 1) carbonyl stability and 2) leaving group ability. • Amides are least reactive this is because the nitrogen is good electron donating group on resonance hence stabilizes the starting material and increase the energy barrier, moreover NH2 is a poor leaving group hence increase the energy of Transition state therefore increase the overall energy. The overall reaction rates decreses and amides become least reactive towards nucleophilic acyl substitution reaction. • Acyl chloride are most reactive as chlorine present here is a good leaving group hence making the energy barrier vof second step very small. Since chlorine is electronegative bin nature so it withdraws electron and hence makes the carbonyl carbon more electrophilic and hence destabilize the resonance and hence the energy barrier decrease and overall reaction rate increase. Therefore, acid halides are most reactive towards nucleophilic acyl substitution reaction.