4- Hydroxycoumarin, tautomerism

The Knoevenagel reaction between o-hydroxyaryl aldehydes and ketones and substituted acetonitriles affords high yields of 3-substituted coumarins in aqueous alkaline media <96H(43)1257>, whilst 4-hydroxycoumarins have been elaborated to pyrano [3,2-c]benzopyran-5-ones by reaction with aromatic aldehydes and malononitiile <96P148>. The imine (10) resulting from the complex reaction of o-hydroxyacetophenone with malononitrile undergoes a 1,5-tautomeric shift in solution <96JCS(P1)1067>. 

Also, (5-phenyl-l,3,4-oxadiazol-2-yl)-7-hydroxycoumarin is a tautomeric compound. In dilute solutions it is almost totally present in its protonated nitrogen tautomeric form. The deprotonation is a reversible process (Scheme 2). Quantum-mechanical calculations were carried out and correlated with experimental observations <2000SAA1773>. 

The tautomerism of 4-hydroxycoumarins has been extensively studied (63AHC( 1)339). From recent IR studies, it appears that 4-hydroxycoumarin (243) exists as this tautomer in chloroform, dioxan and DMSO solutions. Evidence supporting the presence of the 2-hydroxychromone tautomer (244) was not obtained. However, (244) is present in anhydrous, solid state 4-hydroxycoumarin (82JHC385). From the H NMR spectrum of (243) in CD3OD solution, the presence of the chroman-2,4-dione tautomer (245) has been claimed (76MI22202). 

Aminochromone (249) is potentially tautomeric with 2-imino-4-hydroxycoumarin (250). From their IR spectra, 2-acylaminochromones (251 R = OEt or Me) were shown to exist in the form shown, since very intense absorptions at 1635 cm-1, characteristic of a chromone carbonyl group, were observed (67KGS782). 

Thus, with methyl and also ethyl cyanoacetate, the anilinomethylene chromonedione (220) (this form has been found94 to predominate in dimethylsulfoxide solution rather than the tautomeric structure of the formal SchifFs base from 3-formyl-4-hydroxycoumarin and aniline) yields, initially, with potassium hydroxide in DMF, following hydrolysis, the pyronocoumarin 221. 

A series of 4-hydroxycoumarins (93) have been synthesized and then tautomeric equilibria with the 2,4-dione and 2-hydroxy-4-keto forms have been studied by NMR and by MNDO calculations.137... 

X,Y=0,S,Se,Te], has been undertaken.628 The stabilities of different tautomeric forms of 4-hydroxycoumarins have been evaluated629 by MNDO calculations, and the four lowest-energy oxo-hydroxy tautomers of 5-fluorouracil have been studied630 using density functional methods. Semiempirical calculations have been carried out on the keto-enol tautomerism of triazolopyrimidines.631 A base-catalysed keto-enol tautomer-ism has been proposed632 to be responsible for the observed deuterium exchange of the hydrogens at the 3-position of diazepam when the molecule is treated with alkaline deuteriated methanol. 

Extensive studies involving 57 aryl-substituted 4-hydroxycoumarins and using electrospray ionization (ESI) mass spectrometry have allowed the effect of the substituents in the aromatic ring on the fragmentation patterns to be determined. Deuterated compounds were used to prove some of the proposed fragmentation pathways, and the effect of tautomerism on the formation of quasimolecular ions and subsequent fragmentation was explained <2004EJS523>. 

Tautomerism between 4-hydroxycoumarins and 2-hydroxychromones has been investigated extensively by deuterium labeling, 13C NMR, and infrared (IR) spectroscopy <1982JHC385, 1982JHC475>. Computational studies now support the idea that 4-hydroxycoumarins are more stable than 2-hydroxy chromones <1997CJC377>. 

Tautomerism in the benzopyranone 72 has been studied computationally, and tautomer 72 is calculated to be 1.4kcalmol 1 more stable than 73 <1994JCS(P2)2587>. 3-Acetyl-4-hydroxycoumarin has been studied using UV spectroscopy and by computational methods < 1997CJC365, 2000JR0793>. Tautomer 74 is favored in nonpolar solvents such as CCI4 or hexane. In polar solvents, 75 is favored. Computational studies at both semi-empirical and ab initio levels predict 74 and 75 to be of comparable stability, and significantly more stable than all other possible tautomers. 

Structural studies on several hydroxycoumarins have ascertained that the significance of keto-enol tautomerism, H-bonding and H-D exchange is dependent on the position of the hydroxy group <97CJC365, 377>. 

The tautomeric form of 4-hydroxycoumarin (103), acting as a cyclic ) -keto ester, was condensed with aldehydes and urea or thiourea in the presence of basic alumina by heating for 4-6 h at 110-120 °C to give benzopyrano[4,3-[Pg.85]

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