Unique Charge-Separated Pyridinium-Barbituric Acid Zwitterions Branko S. Jursic,* Donna M. Neumann, Zakhia Moore, and Edwin D. Stevens Department of Chemistry, University of New Orleans, New Orleans, Louisiana 70148 bsjcm@uno.edu Received September 24, 2001 Abstract: A synthetic procedure for the preparation of the unusual charge-separated pyridinium barbiturate zwitterion 2 from 1,3-dimethylbarbituric acid and 2-pyridinecarbalde- hyde in methanol was developed. The structure of the compound was confirmed with X-ray analysis to demonstrate the strong charge separation throughout the molecule. One would expect that this charge separation would increase its reactivity; however, contrary to this expectation, the com- pound is very stable in acidic media, and in the presence of a base, decarbonylation occurs on one barbituric acid while the zwitterionic moiety of the molecule stays intact. Pyridinium zwitterions are widely used in organic synthesis. 1 Usually, these compounds are very reactive species that should be kept at low temperatures and in an inert atmosphere. The majority of these zwitterions are synthesized by first preparing the pyridinium salt, followed by the elimination of an acid in reaction with a base. However, there are some other routes that are one- step syntheses that utilize the capability of pyridine derivatives to add to reactive double bonds or to trap carbenes. 2 The 1,4-dihydropyridine addition to alkoxy- carbene complexes of transition metals has been shown to produce pyridinium zwitterions whose negative charge resides on the transition metal, and as such, they are used for selective cyclopropanation. 3 In the majority of cases, the negative ion is on the carbon attached to the pyridinium nitrogen and delocalized by the presence of electron-withdrawing substituents. 1 Pyridinium-cyclopentadienylide is probably the most theoretically explored pyridinium zwitterion with aro- matic stabilization of a negative charge. 4 Yet, even in this case, the molecule has low stability and little is known about its reactivity. 5 To make pyridinium cyclopentadi- enylide sufficiently stable for structure determination in order to evaluate its reactivity, the cyclopentadienide moiety must have strong electron-withdrawing groups, as in the case of pyridiniotetrabromocyclopentadienides. 6 Here we present our method for the preparation of a pyridinium zwitterion (2) with an aromatic stabilization of the negative charge 7 (Scheme 1). This compound was synthesized through controlled condensation between 1,3- dimethyl barbituric acid and 2-pyridinecarbaldehyde. There are previous data that suggest that if the reaction between the barbituric acid derivative and an electron- rich aromatic aldehyde is performed, then the Knoev- enagel condensation 8 product 4 must be the major product isolated (Scheme 2). 9 However, there are some cases of unexpected condensation products, as in the case of electron-poor aromatic aldehydes like nitrobenzalde- hyde, when the double addition product of type 1 is obtained (Scheme 1). 10 Considering the similarities in the electronic properties of 2-nitrobenzaldehyde and 2-py- ridinecarbaldehyde, it should be expected that the iso- lated product of the condensation between 2-pyridine- carbaldehyde and substituted barbituric acids should be of type 1. This, however, is not the case. In almost quantitative yield, the isolated product of this condensa- tion is 2. Our attempt to actually isolate the Knoevenagel con- densation product 4 in the reaction between 1,3-dimethyl barbituric acid and 2-pyridinecarbaldehyde was not successful, regardless of the nature of solvent or base and acid used in this reaction. From NMR spectra taken during the reaction, we know that intermediate 4 is formed and almost instantly consumed in nucleophilic addition of the barbituric acid (product 1). When a better nucleophile is not present in the reaction mixture, then the nitrogen of the pyridine moiety of 4 acts as a nucleophile to another molecule of 4, producing the pyridinium zwitterion 5, which rearranges into the more stable pyridinium zwitterion 2. Both of these zwitterions contain negatively charged barbituric acid rings. Although we do not have direct evidence for the for- mation of pyridinium zwitterion 5, we have indirect ex- perimental information that strongly supports its exist- ence. For instance, if the reaction is performed in acetic acid, then the practically insoluble polymeric product was obtained. 11 Another indication is that it was not possible to prepare type 2 zwitterions if 1-methyl, 1-phenyl, or (1) (a) Litvinov, V. P. Russ. J. Org. Chem. 1993, 29, 1722-1765. (b) Litvinov, V. P. Russ. J. Org. Chem. 1994, 30, 1658-1683. (c) Litvinov, V. P. Russ. J. Org. Chem. 1995, 31, 1301-1340. (d) Litvinov, V. P. Zh. Org. Chem. 1997, 33, 903-940. (2) For instance, see: (a) Visser, P.; Zuhse, R.; Wong, M. W.; Wentrup, C. J. Am. Chem. Soc. 1996, 118, 12598-12602. (b) Kuhn, A.; Plu ¨ g, C.; Wentrup, C. J. Am. Chem. Soc. 2000, 122, 1945-1948. (c) Jackson, J. E.; Platz, M. S. In Advances in Carbene Chemistry; Brinker, U. H., Ed.; JAI Press: Greenwich, CT, 1994; Vol. 1, p 89. (3) (a) Rudler, H.; Parlier, A. Trends Organomet. Chem. 1999, 3, 113-164. (b) Rudler, H.; Durand-Reville, T. J. Organomet. Chem. 2001, 617-618, 571-587. 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