Quaternary Ammonium Hydroxides Undergo Elimination Reactions

Hundreds of related compounds were then synthesized. Successful anesthetics obtained by molecular modification were Benzocaine (a topical anesthetic). Novocain (used by dentists), and Xylocaine (one of the most widely used injectable anesthetics). 

Explain why the half-life (the time it takes for one-half of the compound to be metabolized) of Xylocaine is longer than that of Novocaine. 

10 QUATERNARY AMMONIUM HYDROXIDES UNDERGO ELIMINATION REACTIONS 

A quaternary ammonium ion can undergo an elimination reaction with a strong base such as hydroxide ion. The reaction is known as a Hofinann elimination reaction. The leaving group in a Hofmann elimination reaction is a tertiary amine. Because a tertiary amine is a relatively poor leaving group, the reaction requires heat. 

A Hofmann elimination reaction is an E2 reaction, which means the proton and the tertiary amine are removed in the same step (Section 10.1). Very Uttle substitution product is formed. 

---

Quaternary Ammonium Hydroxides Undergo Elimination Reactions 519... 

Quaternary ammonium hydroxides undergo p-elimination to form an alkene and trimethylamine when heated. This reaction is called the Hofmann elimination. 

Apart from the reactions of diazonium salts, a number of other reactions are known in which the C-N bond is broken. The best known of these is the Hofmann elimination of quaternary ammonium hydroxides (Scheme 2.37). An amine is converted by methylation with methyl iodide to the quaternary ammonium salt ( exhaustive methylation ). The iodide, on treatment with moist silver oxide, forms the quaternary ammonium hydroxide which undergoes a bimolecular elimination to form an alkene. The bimolecular elimination of onium salts yields the least alkylated alkene. This substitution pattern is determined by the ease with which a hydrogen atom can be attacked by the base. 

For a quaternary ammonium ion to undergo an elimination reaction, the counterion must be hydroxide ion because a strong base is needed to start the reaction by removing a proton from a j8-carbon. Since halide ions are weak bases, quaternary ammonium halides cannot undergo a Hofmann elimination reaction. However, a quaternary ammonium halide can be converted into a quaternary ammonium hydroxide by treating it with silver oxide and water. The silver halide precipitates, and the halide ion is replaced by hydroxide ion. The compound can now undergo an elimination reaction. 

The Hofmann elimination reaction was used by early organic chemists as the last step of a process known as a Hofmaim degradation—a method used to identify amines. In a Hofmann degradation, an amine is exhaustively methylated with methyl iodide, treated with silver oxide to convert the quaternary ammonium iodide to a quaternary ammonium hydroxide, and then heated to allow it to undergo a Hofmann elimination. Once the alkene is identified, working backwards gives the stmcture of the amine. 

SOLUTION TO 10a Although an amine cannot undergo an elimination reaction, a quaternary ammonium hydroxide can. The amine, therefore, must first be converted into a quaternary ammonium hydroxide. Reaction with excess methyl iodide converts the amine into a quaternary ammonium iodide, and treatment with aqueous silver oxide forms the quaternary ammonium hydroxide. Heat is required for the elimination reaction. 

Quaternary ammonium hydroxides and amine oxides undergo E2 elimination reactions known as Hofmann elimination reactions and Cope elimination reactions, respectively. In both reactions, the proton from the j8-carbon bonded to the greater number of hydrogens is removed. 

Notice that the bromoalkane (Structure 2.7) can be transformed into the quaternary ammonium bromide (Structure 2.8) by treatment with trimethylamine by an Sn2 reaction. Treatment of 2.8 with hydroxide anion forms the quaternary ammonium hydroxide, which undergoes elimination on heating. 

A quaternary ammonium hydroxide can undergo an E2 reaction known as a Hofmann elimination if they are heated. Hydroxide ion removes a proton from the 8-carbon bonded to the most hydrogens. 

We shall discuss later how to make ammonium hydroxide salts such as R4N+ OH, which are known as quaternary ammonium salts because N has four alkyl groups attached to it, and which undergo Hofmann elimination reactions on heating. 

---