5- barbituric acid, solid phase

In the solid state, barbituric acid exists as two anhydrous forms (polymorphs I and II) (Scheme 20) and a dihydrate phase. They all display the trioxo structure 28 shown by X-ray difiraction studies (Scheme 21) (2008CGD1454). 

Two important papers by Gobetto et al. belong to this section. In the first one, the tautomerism of barbituric acid (33) was discussed (08CGD1454). In the solid state, the barbituric acid is well known to exist as two anhydrous forms (polymorph I and II, which differ in the HB network) and a dihydrate phase. They all display the trioxo structure 33a of Figure 7 shown by X-ray diffraction studies. In solution, on the contrary, the barbituric acid may exist as 11 possible structures (Figure 7) because of tautomeric equilibria. 

By ball-mill grinding a commercial sample of barbituric acid in its tri-0X0 form 33a (polymorph II, 99%) for 24h, a new compound has been isolated. The new phase has been identified as the trihydroxyl isomer 33k, using solid-state NMR ( H, and N). In solution, the trihydroxyl isomer immediately converts to the trioxo form as demonstrated by H NMR experiments in protic, aprotic, and amphiprotic solvents (D2O, methanol-d, DMSO-r/g, acetone-d ). 

A new tag strategy, termed syndiesis based on affinity separation (SAS) , was developed for high throiq)ut synthesis of organic conq)oimds. In this method, the desired tagged conq)ound was separated from the reaction mixture by solid-phase extraction using specific molecular recognition. The interaction between a crown ether (32-crown-lO) and ammonium ion and the interaction between a barbituric acid derivative and its artificial receptor were used for SAS. 

---