Pyron-ring substituted coumarins

The Pechmaim reaction has found extensive appHcations for the synthesis of numerous coumarin derivatives (39). Coumarin derivatives substituted in the pyrone ring can be obtained by condensing phenol with beta-ketoesters. For example, 4-methylcoumarin (3) is obtained with ethyl acetoacetate... 

Coumarins belong to a group of compounds known as the benzopyrones, all of which consist of a benzene ring joined to a pyrone. They may also be found in nature, in combination with sugars, as glycosides. They can be categorized as simple fura-nocoumarins, pyranocoumarins, and coumarins substituted in the pyrone ring (Murray and others 1982). 

Two studies correlate substituent-induced chemical shifts (SCS) with substituent parameters. Gottlieb et al. (33) investigated the SCS on the pyrone ring carbons C-2, C-3, C-4, C-9 and C-10 in 6- and 7-substituted coumarins, and found good correlations of the ring-junction atoms C-9 and C-10 with the Hammett constants Cp+ and of C-2 and C-4 with cm, and, separately, with cp. More-... 

N,iV-Disulfonyl ynamides react with salicylaldehydes through a keteni-mine intermediate in the presence of triethylamine giving access to 3-substituted iminosulfonylcoumarins (140BC3986). Biscoumarins fused at the pyrone ring arise from the indium(III) trifluoromethanesulfonate-catalyzed reaction of methyl coumarin-3-carboxylate with phenols, in good yields (14JOC8723). A library of 3,3 -biscoumarin-based protein kinase inhibitors is achieved from the condensation of 2 -hydroxyacetophenones... 

After the separation of furanocoumarin, spectroscopic methods can be used to identify and quantify these phenolic compounds. Coumarin shows absorption bands at 274 and 311 nm, which have been attributed to the benzene and pyrone rings, respectively. Methyl substitution at C-5, C-7, or C-8 leads to a bathochromic shift of the 274 nm maximum but leaves the 311 nm maximum practically unchanged [68]. 7-Oxygenated coumarins show strong absorption bands at about 217 and 315-330 run with weak peaks or shoulders at 240-250 nm. Linear furanocoumarins show four zones of absorption at 205-225, 240-255, 260-270, and 298-316 nm. Angular furanocoumarins can readily be distinguished from linear forms since the maxima at 242-245 and 260-270 are absent [69]. 

The mass spectrum of 2-pyrone shows an abundant molecular ion and a very prominent ion due to loss of CO and formation of the furan radical cation. Loss of CO from 4-pyrone, on the other hand, is almost negligible, and the retro-Diels-Alder fragmentation pathway dominates. In alkyl-substituted 2-pyrones loss of CO is followed by loss of a hydrogen atom from the alkyl substituent and ring expansion of the resultant cation to the very stable pyrylium cation. Similar trends are observed with the benzo analogues of the pyrones, although in some cases both modes of fragmentation are observed. Thus, coumarins. 

Coumarin (11.46), iscoumarin (11.47), and chromone (11.48) should each be more reactive than the corresponding pyrone, and consideration of conjugative effects indicates substitution to be preferred at the 3-position of 11.46 and 11.48, and at the 4-position of 11.49. Isocoumarin (11.47), in which the oxygen lone pair is less readily delocalized into the benzenoid ring, should be more reactive than the other two isomers. Substituents in these molecules will have very marked directional effects because of significant bond fixation. 

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