Question

The given reaction is a Mannich reaction. The starting material is 8-hydroxy-1,2,3,4-tetrahydroquinoline. This molecule possesses two key functionalities required for a Mannich reaction:

1. A secondary amine group (the -NH in the tetrahydroquinoline ring).
2. An activated aromatic ring (the benzene ring with a hydroxyl group, -OH, which is a strong activating group).

The other reactant is formaldehyde (HCHO), and the reaction is carried out in acidic conditions (H$^+$).

What is the final product?

Answer 1

6-hydroxy-1,2,3,4,4a,10b-hexahydro-10H-benzo[c]quinolizine

Answer 2

The reaction shown is a Mannich reaction, which involves the aminoalkylation of an active hydrogen compound with an aldehyde and an amine. In this case, the starting material, 8-hydroxy-1,2,3,4-tetrahydroquinoline, serves as both the secondary amine component (due to the -NH group in the saturated ring) and the active hydrogen compound (due to the electron-rich phenolic benzene ring). Formaldehyde (HCHO) is the aldehyde, and H$^+$ indicates acidic conditions.

The reaction proceeds in two main steps:

1. Formation of an iminium ion: The secondary amine group (-NH) of 8-hydroxy-1,2,3,4-tetrahydroquinoline reacts with formaldehyde in the presence of acid to form an iminium ion. The nitrogen atom becomes part of a C=N$^+$H-CH$_2$ structure (simplified to N=CH$_2$).

2. Intramolecular Electrophilic Aromatic Substitution: The iminium ion acts as an electrophile and attacks the activated benzene ring of the same molecule. The hydroxyl group (-OH) on the benzene ring is a strong activating group and directs electrophiles to the ortho and para positions. In 8-hydroxy-1,2,3,4-tetrahydroquinoline, the para position to the -OH group (position 5) is the most activated and sterically accessible site for electrophilic attack. The iminium carbon (from formaldehyde, -CH$_2$-) forms a new bond with this para carbon (C5). This results in an intramolecular cyclization, forming a new 6-membered ring.

The product is a tetracyclic compound, specifically named 6-hydroxy-1,2,3,4,4a,10b-hexahydro-10H-benzo[c]quinolizine.

The structure of the product is:

The final product is a tetracyclic system with the hydroxyl group retained.

The reaction is:

\begin{center}
\includegraphics[width=0.8\textwidth]{mannich_reaction_product.png}
\end{center}

The product formed is:

\begin{center}
\includegraphics[width=0.8\textwidth]{mannich_product_final.png}
\end{center}