Coumarins bearing substituents in the 4-position or in both the 3-and 4-positions are readily obtained from reactive phenols via von Pechmann condensation with P-keto esters (1). No such effective, one-step method has been available for the conversion of polyhydric phenols to 3,4-unsubstituted coumarins.The von Pechmann condensation of phenols with malic acid in hot, concentrated sulfuric acid gives low yields of 3,4-unsubstituted coumarins (l), and sometimes fails completely, e.g. , with phloroglucinol (Ia) or its dimethyl ether (2). Thompson and Edee (3) found that P-cresol was converted to 6-methylcoumarin in 80% yield when they heated it with maleic o r fumaric acid and 72% sulfuric acid. The application of this process to a polyhydric phenol has been studied by George (4), who reported that resorcinol, when heated with fumaric acid and concentrated sulfuric acid, was converted to 7-hydroxycoumarin (umbelliferone) in 70% yield.Attempts to duplicate George's results, including wide variation of reaction conditions, have failed to produce any 7 -hydroxycoumarin. Similarly, no 8-methylumbelliferone (IIIb) was obtained when 2 -methylresorcinol (Ib) was heated with maleic acid in 75% sulfuric acid. We conclude that condensation of polyhydric phenols with maleic o r fumaric acid does not show promise as a method of coumarin synthesis.In 1917, Fischer and Nouri (5) obtained 5,7-dihydroxy-4-phenylcoumarin from the zinc chloridecatalyzed condensation of phloroglucinol with ethyl phenylpropiolate. There have been no further applications of that reaction, nor has the use of other propiolate esters been reported. Base catalyzed Michael addition of phenols to ethyl propiolate is, of course, a well known (6) step of a synthetic sequence leading to chromones. We wish to report that acid catalyzed condensation of ethyl propiolate (n) (7) with reactive phenols appears to be an effective method for the preparation of 3,4unsubstituted coumarins.For example, 5,7 -dihydroxycoumar in ( IIIa) was obtained in 89% yield from the condensation of phloroglucinol dihydrate (Ia) with ethyl propiolate (II), in the presence of zinc chloride.The dihydroxycoumarin was characterized by conversion to a diacetate in 83% yield. In an extension of the new process, we found that 2-methylresorcinol (Ib) also condenses with ethyl propiolate when heated with zinc chloride. Better results were obtained, however, when equimolar quantities of 2 -methylresorcinol (Ib) and ethyl propiolate (II) were heated in 15% ethanolic sulfuric acid.8 -Methylumbelliferone (IIIb),, was obtained in 75% yield. The product was characterized by conversion to an acetate.For comparison, it i s interesting to note that Seshadri and Venkateswarlu (10) heated 2-methylresorcinol with malic acid in concentrated sulfuric acid to obtain a sample of 8-methylumbelliferone which melted 28" lower. They did not state the yield. Thus acid catalyzed condensation with ethyl propiolate appears to be a superior method for the introduction of an unsubstituted a-pyrone ring on a reactive phe...

Department of 4.6-Dibromoresorcinol dimethyl ether has been converted into 4.6-dihydroxyisophthalaldehyde (1 1 ) by lithiumbromine interchange, formylation, and demethylation. Similarly the 5-methyl and 5-methoxy-derivatives were prepared, all in good overall yields. Three dioxa-anthracenediones have been prepared from the isophthalaldehydes. Low-temperature lithium-bromine interchange, formylation, and selective demethylation provided a route to 5-brorno-3,4-dimethoxysalicylaldehyde (1 4), which has potential as an intermediate for the synthesis of oxygen heterocycles. Chemistry, Kalamazoo College, Kalamazoo, Michigan 49001, U.S.A. WE have prepared 4,6-dihydroxyisophthalaldehyde (1 1)and its 5-methyl and 5-methoxy-derivatives, compounds which have potential as synthetic intermediates.* Treatment of 1,5-dibrom0-2,4-dimethoxybenzene (1) with an excess of butyl-lithium and then N-methylformanilide gave 4,6-dimethoxyisophthalaldehyde (4) (72%) and 2,4-dimethoxybenzaldehyde (1 1 yo). Demethylation of (4) with aluminium bromide in nitrobenzene was accompanied by nuclear bromination to give (9) (76%). Aluminium chloride in 1,2-dichloroethane gave partial demethylation to afford (10) (5y0), but in nitrobenzene dihydroxyisophthalaldehyde (1 1) (87%) was formed.To examine the scope of this reaction the &methyl and 5-methoxy-derivatives of (1 1) were prepared.* The use of (11) in a study of cobalt(II1) chelates has been reported,l but its source could not be ascertained (M. Colvin, personal communication).Bromination of 2,6-dimethoxytoluene gave (2) (78%) which was treated with an excess of butyl-lithium followed by NN-dimethylformamide to give (5) (74%). Demethylation of this with aluminium chloride in nitrobenzene proceeded smoothly to give (12) (89%).The trimethoxyisophthalaldehyde (6) was prepared similarly (55%) from 4,6-dibromopyrogallol trimethyl ether 3 (3) ; on demethylation it gave 4,6-dihydroxy-5-methoxyisophthalaldehyde (13) (67%).The use of these intermediates in the synthesis of symmetrical oxygen heterocycles was exemplified by condensing 4,6-dihydroxyisophthalaldehyde (1 1) with acetic Lanhydride under Perkin conditions to give the

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The first parent benzodifuran (XVI) and three di‐ and trimethylated derivatives have been synthesized and screened for erythemal activity (negative response). Two benzodifurans were prepared from resorcinol and 2‐methylresorcinol by acetylation, Fries rearrangement, alkylation of the resulting 4,6‐diacetylresorcinols with ethyl bromoacetate, saponification, and then cyclization of the (4,6‐diacetyl‐1,3‐phenylenedioxy)diacetic acids. Another was prepared from the Claisen rearrangement product of 1,3‐bis(allyloxy)‐2‐methylbenzene by acetylation, bromina‐tion, and cyclization. Ozonolysis of the Claisen rearrangement product gave additional support to the formulation of o‐hydroxyphenylaeetaldehydes as cyclic hemiacetals. The parent benzodifuran was synthesized from 5‐formyI‐6‐hydroxybenzofuran, which was prepared in two steps from 5‐bromo‐6‐methoxybenzofuran. Alkylation of the former with ethyl bromoacetate, saponification, and cyclization furnished benzo[1,2‐b.5,4‐b ]difuran. The ultraviolet and nuclear magnetic resonance spectra of the four benzodifurans are compared.