Iminofurandione - Pyrroledione Rearrangement: a Semi-empirical Molecular Orbital Study

Iminobenzylfurandiones 1, obtainable e.g. by reaction of 4-acyl-furan-2,3-diones with tosylsulfinylamines or arylalkylcarbodiimides,  thermally rearrange to 4-acyl-pyrrolediones 2.

 

1. a Cornforth - type rearrangement involving opening of the lactone ring
2. a sequence consisting of electrocyclic ring closure - rearrangement - electrocyclic ring opening
3. a bimolecular reaction involving nucleophilic addition of the imino nitrogen atom of one molecule of 1 at C5 of a second molecule 1
4.  lactone ring opening catalysed by traces of nucleophiles (H₂O, amines)

    1. a Cornforth - type rearrangement involving thermal opening of the lactone ring

    2.  electrocyclic ring closure - rearrangement - electrocyclic ring opening

Figure 1. Transition state for lacton ring opening (leading to elimination of CO rather than rearrangement).
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Rearrangement  1 -> 2 via a Cornforth - type mechanism appears thus highly unlikely.
 

Figure 2. Transition state for electrocyclic ring closure of 1 (rate determining step)
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Formation of compound 2 by  this mechanism, therefore, would require prohibetively large activation energies and, thus, is highly unlikely.

In analogy to the unusually fast  Chapman-like rearrangement of some 5-alkoxy-2-aryl-1,3,4-oxadiazoles in the solid state which were shown to proceed in a bimolecular, double ionic fashion involving two molecules of the starting material, ⁶ a bimolecular mechanism is also conceivable for the present rearrangement reaction:

Nucleophilic attack of the imino nitrogen at C2 (the lacton carbonyl carbon) of a second molecule 1 would lead to a zwitterionic intermediate; cyclisation and elimination of this intermediate yields a mixture of starting material and product. Energetics as well as structural features for such a reaction sequence are summarised in Table 2 . Activation energies are fairly low; the rate determining step appears to be the formation of the primary adduct (tetrahedral intermediate).

Figure 3. Transition state for the nucleophilic attack between two molecules 1 (rate determining step).
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Based on the computed activation energies a bimolecular mechanism involving two molecules 1 seems to be a quite reasonable mechanistic possibility. However, recent experiments on highly purified 1 indicate that some catalysis is necessary to initiate the rearrangement.

The interpretation of these results is hampered by the well known problems of the AM1 method in the description of carbonyl - nucleophile reactions, especially the considerably overestimated stability of tetrahedral intermediates. Consequently, activation energies for processes leading to the decomposition of such tetrahedral intermediates are grossly overestimated. Furthermore, some of the tetrahedral intermediates obtained by the calculations are more stable than the reaction product 2 (see Table 3).

As an example, the transition state for elimination of H₂O from the C2 - hydrate of 4-formyl-pyrrole-2,3-dione to 2 + H₂O (the rate determining step ) is shown in Figure 4.

This mechanism is most likely on the basis of experimental observations, the calculations, however, are in favour of a bimolecular mechanism involving TWO molecules of the furandione. Whether the high activation energies found for the nucleophile - catalysed pathway are an artifact of the semi-empirical method or an intrinsic property of the molecules is still under investigation.

The results for bimolecular mechanisms are less clearcut:

The calculations are in favour of a pathway involving two molecules 1 (nucleophilic attack of the imino nitrogen atom of one molecule 1 at C2 of the second one).  In contrast, experiments hint towards catalysis by traces of nucleophiles.

A distinction between these two possibilities is hampered by the shortcomings of the semi-empirical methods in describing carbonyl - nucleophile reactions.

Further experiments as well as ab initio calculations  to gauge the AM1 results are in progress.