Mississippi College

Pseudoacids.

Preliminary Structural Studies:  Our group is interested in organic structures featuring variable C-O bond lengths which correlate with reactivity. We have explored the relationship between leaving group abilities of various derivatives of 2-hydroxydihydropyranyl ethers [seeActa Crystallographica (1990),B46, 629-637].

We find that the rates of E1-type elimination reactions correlate directly with the length of the exocyclic (x) C-O bond and inversely with the length of the endocyclic (n) C-O bond.. This suggests that the ground state structures begin to resemble the reaction transition state forms as the leaving group ability increases (stability of conjugate base).

Pseudoacids.  This class of molecules may be thought to be related to the acetals and ketal with each of the interacting functional groups in the next higher oxidation state.  Oxocarboxylic acids of the aldehyde-acid and keto-acid types can cyclize to form "lactols" (or "phthalides" in ortho-disubstituted aromatic cases).  The more stable rings are those with five and six atoms.

This relatively understudied class of organic substances also shows a sensitive structural dependency and reaction rate variability as a function of substitution. We have completed structures on a number of aromatic and aliphatic pseudoacids, esters and anhydrides. While 'normal' acids, in their pure condensed phases, form binary dimers with the carboxylic acid groups coplanar, some pseudoacids form binary dimers involving necessarily non-planar complementary H-bonding. Structural results from a series of pseudoacids has appeared ("Pseudoacids. I. 4- and 5-oxoacids", Valente, E. J., Fuller, J. F., Ball, J. D., Acta Cryst. B54, 162 - 173[1998]) and the derivatives of the pseudoacids of o-acylbenzoic acids ("Pseudoacids. II. 2-Acylbenzoic Acid Derivatives", Valente, E. J., Martin, S. B., Sullivan, L. D., Acta Cryst. B54, 264 - 276 [1998]). The structures may be examined in more detail for the interested.

This work was followed by an exploration of some of the factors that influence the open-cyclic equilibrium in solutions of ortho-disubstituted aryl systems forming pyran rings.  These are contained in the paper "Pseudoacids. III. Formation and structures of new cyclic oxocarboxylic acids.", Cooper, W. J., Smith, T. N., Barker, A. K., Webb, J. A., Valente, E. J., J. Chem. Crystallogr. 33, 373-382 [2003]. In this work, we discuss the two crystalline forms of 4,4-dimethyl-3-hydroxy-3,4-dihydroisobenzopyran-1-one, one having two molecules in the asymmetric unit , and the other has one molecule in the asymmetric unit .  Both form complementary Hydrogen-bonded dimers.
arylpyran pseudoacid

Most recently, we have explored the synthesis of the fist "dipseudoacid" of the arylpyran class.  We chose the dehydration resistant platform like that in the previous system, and followed a route that involved symmetric disubstitution from benzene.  This synthesis is the subject of an upcoming article (Liskin, D. V., Valente, E. J., J. Mol. Struct. ).
arylpyran dipseudoacid 


(Rasmol/raswin can be used to view the .pdb files of the structures interactively.)
 

For more information, send email to valente@mc.edu.