Though not strict but rather an intuitive concept, the analogy (structural, electronic, stereochemic — Organic Chemistry Chemistry Question
The analogy in organic chemistry
Though not strict but rather an intuitive concept, the analogy (structural, electronic, stereochemical) is widely used by chemists for reasoning. For example, organic chemists often predict new reagents or even reactions by analogy with known ones.
An important sort of analogy is heteroanalogy – the similarity of compounds or reactions differing by substitution of an atom or group by another atom or group having the same type of bonding.
Thus, heteroanalogues of aldehydes are iminium salts, e.g. a well-known Eschenmoser’s salt CH2=NMe2 +I–.
Which type of reagent is the cation of Eschenmoser’s salt?
Electrophile nucleophile free radical
Lewis acid oxidant protecting group
Model Answer
Eschenmoser’s salt is an iminium salt, which involves a heteroanalogue of carbonyl group. Thus, Eschenmoser’s salt is an electrophile with electrophilic carbon center similar to the carbonyl carbon. Formally, it should behave as a stabilized carbenium ion, as is well seen by considering the resonance forms:
[VISUAL]
Due to very high π-donicity of dimethylamino group, the first form predominates, and thus nucleophilic properties, which may be attributed to the second form, are virtually missing. It can be considered a Lewis acid, as any C-electrophile is, due to apparent ability to combine with bases, e.g. hydroxide ion or water.
Thus, electrophile is the true answer, and Lewis acid and/or nucleophile can be regarded as valid additional answers.
Write by analogy the reaction of Eschenmoser’s salt with acetone. Why does this reaction not require a catalyst?
Model Answer
No catalyst is required because iminium salt is already strongly polarized, and carbon atom is sufficiently electrophilic to attack carbonyl group without any additional activation by catalysts. In the reactions with aldehydes or ketones the iminium salt serves as a heteroanalogue of the protonated carbonyl compound, with the double carbon-nitrogen bond strongly polarized due to the positive charge at heteroatom. Therefore, the iminium salt is already reactive enough to take part in electrophilic attack at enol to form the so called Mannich base, which is itself a heteroanalogue of the aldols.
[VISUAL]
What products are formed on prolonged heating of 1,5-hexadiene substituted at C1 with one deuterium atom in inert atmosphere (possible isotope effects are to be neglected)?
Model Answer
In the Cope rearrangement, it is highly important to realize that the reaction is an equilibrium, which is perfectly evident from the fact that the reactant and product are the same compound (or the same type of compound, if a substituted diene is used). Thus, the forward and the reverse transformations are the same reaction. In the case of degenerate reaction (when reactant and product are the same, if isotope effects are neglected), it is evident that equilibrium constant is unity.
[VISUAL]
Thus, the result would be an equimolar mixture of 1- and 3-deuteriohexadiene-1,5.
Complete the reaction
[VISUAL]
Model Answer
Unlike the Cope rearrangement, oxo-Cope rearrangement involves two different compounds (belonging to different classes), thus the reversibility is not evident. In the case of allylic phenol ether hetero-hexadiene fragment is formed by allyloxy chain and one of the double bonds of benzene ring:
[VISUAL]
As the initial keto-form of phenol is immediately transformed into much more stable normal phenol (enol) form, the arrangement of double bonds for Cope-Claisen rearrangement disappears, and the whole reaction becomes irreversible.
Your task would be to imagine how the following domino-process, which is initiated by a drop of strong acid and a dehydrating agent, such as HC(OEt)3, takes place
[VISUAL]
Write the steps involved in this process.
Model Answer
The domino-reaction starts from the formation of a cyclic iminium salt similar to the Eschenmoser’s salt, with triethyl-orthoformate serving as a dehydrating agent. In this salt there are two double bonds at a distance required for the Cope rearrangement, thus here we have the aza-Cope rearrangement. A new iminium salt is formed, which is readily hydrolyzed to liberate secondary amine and formaldehyde.
[VISUAL]