Coumarin, 7-acetoxy-4- 2- -5-hydroxy

Comforth has reviewed literature reports and independently studied the special cases of reaction of 1 with salicylaldehyde and with 2-acetoxybenzaldehyde. Coumarins (10) are afforded in the condensation of 1 with salicylaldehyde or its imine, whereas when 2-acetoxybenzaldehyde is used, acetoxy oxazolone 12 is the major product. The initial aldol condensation product between the oxazolone and 2-acetoxybenzaldehyde is the 4-(a-hydroxybenzyl)oxazolone 11, in which base-catalyzed intramolecular transacetylation is envisioned. The product 9 (R = Ac) can either be acetylated on the phenolic hydroxy group, before or after loss of acetic acid, to yield the oxazolone 12, or it can rearrange, by a second intramolecular process catalyzed by base and acid, to the hydrocoumarin, which loses acetic acid to yield 10. When salicylaldehyde is the starting material, aldol intermediate 9 (R = H) can rearrange directly to a hydrocoumarin. Comforth also accessed pure 4-(2 -hydroxyphenylmethylene)-2-phenyloxazol-5(4//)-one (13) through hydrolysis of 12 with 88% sulfuric acid. 

Deacetylation of 4-[(o-acetoxy)benzylidene]-2-phenyl-5(47/)-oxazolone also immediately affords 602. The starting oxazolone was obtained by cyclodehydration of the corresponding cinnamic acid precursor or by condensation of hippuric acid with 2-acetoxybenzaldehyde in the absence of base. In examples using 2-hydroxy-acetophenone, 4-methyl-3-(acylamino)coumarins are obtained. ... 

A very simple synthesis of coumestrol (228) has been described by Kappe and coworkers (Scheme 46) (74ZN(B)292). It is based upon dehydrogenation of 4-hydroxy-3-phenyl-coumarins to coumestans (720PP233). A number of 2 -hydroxy 3-phenylcoumarins were oxidized with lead tetraacetate to the corresponding coumestans 3-(l-acetoxy-4-methoxy-2-oxo-3,5-cyclohexadienyl)coumarins were obtained as by-products (76BCJ1955). Coumes-tan itself (226) has been obtained by photolysis of the phenol ether (232), which is in turn available from 4-hydroxycoumarin (229) and (diacetoxyiodo)benzene (Scheme 47) (78CB3857) via an iodonium ylide (231). 

A soln. of ethyl 6-acetoxy-3-chloro-4-coumarincarboxylate in THF treated with 0.5 eqs. N-methyl-2-dimethylaminoacetohydroxamic acid in phosphate buffer (pH 7.6), and stirred at room temp, for 1 h ethyl 3-chloro-6-hydroxy-4-coumarin-carboxylate. Y 95%. The method is especially convenient for preferential cleavage of phenol, enol, and oxime acetates in alkali-labile and/or oxygen-sensitive substrates. F.e.s. M. Ono, I. Itoh, Tetrahedron Letters 30, 207-10 (1989). 

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