If an alcohol were to undergo a substitution reaction, which of the following modifications would improve the alcohol's leaving group ability?

Question

Quizplus · Accepted Answer

11ecba2d_127b_f230_a3bf_b77464d9256e_MD0008_00 Substitution reactions require strong nucleophiles and electrophiles and good leaving groups. When a nucleophile attacks an electrophile, a bond is formed between the nucleophile and electrophile whereas the bond between the electrophile and the leaving group is broken. A leaving group containing an electron withdrawing group can enhance the partial positive charge of the electrophile. Leaving groups are weak bases and are able to accept electrons; they often can be stabilized by the delocalization of electrons through resonance and an inductive effect. Alcohols are weak electrophiles and poor leaving groups; therefore, nucleophiles are unlikely to displace the hydroxyl group (-OH). The alcohol can be converted into a mesylate (-SO₃CH₃) to improve its leaving group ability. Mesylates are produced by the reaction of an alcohol with methanesulfonyl chloride and a base, such as triethylamine, and are good leaving groups because the mesylate anion can stabilize the negative charge through resonance. Similar to mesylates, tosylates (-SO₃C₆H₄CH₃) can also be used to make an alcohol a better leaving group. (Choice A) Protecting the alcohol does not make it a better leaving group but rather decreases its reactivity. (Choice B) Deprotonation of the alcohol creates a negative charge on the alcohol oxygen atom, making it a nucleophile rather than a leaving group. Alternatively, protonation of the alcohol would create a strong electrophile and good leaving group in the form of water. (Choice D) Oxidation of the alcohol forms a double bond to the oxygen atom. It makes the carbon bonded to the alcohol oxygen a strong electrophile that is susceptible to nucleophilic attack, but the alcohol leaving group ability is decreased as there are now two bonds holding it in place. Educational objective: Alcohols are poor leaving groups and weak electrophiles. However, an alcohol's leaving group ability can be improved through the formation of a mesylate (-SO₃CH₃) or a tosylate (-SO₃C₆H₄CH₃). Mesylates and tosylates can be produced by the reaction of an alcohol with a base and methanesulfonyl chloride or p-toluenesulfonyl chloride, respectively. The mesylate and tosylate anions can stabilize their negative charges by the delocalization of electrons through resonance.

If an Alcohol Were to Undergo a Substitution Reaction, Which