Recently, several transformations of levulic acid (4-oxopentanoic acid) have been reported in the Jo — Organic Chemistry Chemistry Question
Heterocyclic compounds
Recently, several transformations of levulic acid (4-oxopentanoic acid) have been reported in the Journal of Chemistry (Vietnam). One of them is the synthesis of three hydrazides (RCONHNH2) from levulic acid in which R is one of the followings:
Compound A
[VISUAL]
Compound B
[VISUAL]
Compound C
[VISUAL]
Assuming that you have: inorganic chemicals, levulic acid, other acyclic organic compounds, benzene derivatives (PhCHO, PhNCS, 3-NO2C6H4SO3Na), catalysts (piperidine, TsOH), and solvents.
Provide the synthetic scheme to obtain A. What is the purpose of 1,3-dioxolane ring formation? Write down the reaction equation to prepare TsOH from toluene.
Model Answer
Synthesis of A from levulic acid: [VISUAL]
The purpose of 1.3-dioxolane formation was to protect the carbonyl group from the reaction with NH2NH2.
TsOH preparation from toluene: [VISUAL]
Provide the synthetic scheme to obtain B. What is the reation mechanism using PhNCS? Write down the reaction equation to synthesize PhNCS from aniline?
Model Answer
Synthesis of B from A: [VISUAL]
The reaction of A and PhNCS is nucleophilic addition of the –NHNH2 group to the –NCS group. [VISUAL]
PhNCS preparation from aniline:
PhNH2 + CS2 + NH4OH → PhNHCSNH4 + H2O
PhNHCS2NH4 + Pb(NO3)2 → PhNCS + NH4NO3 + HNO3 + PbS
Provide the synthetic scheme to obtain C. What is the role of 3-O2NC6H4SO3Na? Write down the reaction equation to prepare 3-O2NC6H4SO3Na from benzene. Using signals from proton nuclear magnetic resonance spectroscopy to prove that the reaction with 3-O2NC6H4SO3Na has occurred?
Model Answer
Synthesis of C from levulic acid: [VISUAL]
3-O2NC6H4SO3Na is a dehydrogenation (or oxidation) reagent to convert dihydro-pyridazine into pyridazine ring.
3-O2NC6H4SO3Na preparation from benzene: [VISUAL]
1H-NMR spectrum: Before the reaction, the heterocyclic should provide 2 resonance signals with 2H intensity in the strong field of the two CH2 groups (experimental: 2.57 ppm and 2.83 ppm). After the reaction, these 2 signals should disappear, and two new signals with 1H intensity in the weak field of the two CH groups should appear (experimental: 7.01 ppm and 7.64 ppm).
The three hydrazides (A, B, and C) are reacted with PhCHO to generate corresponding products (E, F, and G). Draw a common reaction mechanism for these transformations. If 4-NO2C6H4CHO or 4-Me2NC6H4CHO was used instead of PhCHO, would the reactions be more difficult or easier to proceed?
Model Answer
Reaction mechanism of R-CONHNH2 with PhCHO: First, the hydrazide -CONHNH2 group performed nucleophilic addition to the C=O group of benzaldehyde, then the dehydration step occurred: [VISUAL]
The electron-withdrawing group –NO2 facilitates the reaction, while the electron-donating group –NMe2 retards the reaction: 4-Me2NC6H4CH=O < C6H5CH=O < 4-NO2C6H4CH=O