THEhf ETIIYL'4TION
May 2U, 1959
2427
O F PYRONONES
(16 1.). Only a small amount of the biologically active ration of the combined n-butyl alcohol extracts yielded 33 material remained in the aqueous phase. The ethyl acetate nig. of an almost colorless oil. G . Isolation of Crystalline Bean Factor 11.-The bean extract, which was very active in the bioassay, was evapofactor I1 fraction (33 mg.) from countercurrent distribution rated t o dryness i n vacuo. D. Silicic Acid Chromatography.-A mixture of 133 g. was dissolved in acetonewater (95: 5), and the solution was of silicic acid26 and 67 E[. of celite was tamped dry into a passed over a small charcoal column. The residue (15 mg.) column 3 X 90 cm. which was washed with successive por- obtained on evaporating the column effluent was extracted tions of ethyl ether (75 ml.), ethyl ether-acetone (75 ml.), with warm ethyl acetate, and the solution filtered. The ethyl ether (50 ml.) and chloroform (100 ml.). The residue volume of the filtrate was reduced to 1 ml. in a stream of from the ethyl acetate extract at pH 2 was adsorbed on 15 g. nitrogen and 1 ml. of petroleum ether was added.28 A of silicic acid-celite ( 2 : l ) , and the mixture transferred to flocculent precipitate separated on standing. I t was rethe column. The column was developed with chloroform moved and petroleum ether was again added to incipient (1 l . ) , increasing concentrations of from 5 t o 28y' ethyl ace- turbidity. On standing and cooling a crystalline precipitate tate in chloroform (2.2 l.), 307, ethyl acetate in chloroform separated. Two milligrams of bean factor I1 was recovered (10.4 1.) and ethyl acetate (1 1.). Seventy-eight 200-ml. as platelets which melted with decomposition from 250255". fractions were collected. Methylation.-N-Nitrosomethylurca (26 mg.) dissolved Evaporation of fractions 17-24 yielded 0.87 g. of a brown oil which was highly active in the bioassay for d - 5 but only in ethyl ether was treated with 1 ml. of 50'Jo potassium slightly active for d-1. The active material in this fraction hydroxide, and the diazomethane generated was distilled into ethyl ether according t o a procedure d e s ~ r i b e d . Ap~~ is referred to as bean factor 11. Evaporation of fractions 25-53 yielded 1.14 g. of a brown proximately 0.5 mg. of bean factor I1 was triturated with oil \%hichwas highly active in the bioassay for both mutants, the diazomethane solution. The solvent and excess diazod-1 and d-5. The active material in this fraction is re- methane were removed by evaporation. The solid residues ferred to as bean factor I. Fractions 54-73 also contained mixed with a small quantity of Florisi130were slurried in petroleum ether28 and added to a Florisil column ( 1 X 5 cm.). small quantities of bean factor I. E. Charcoal Chromatography.-Sixty-seven g. of char- The column was developed with 25y0 ethyl ether (10 ml.), coal and 133 g. of celite were slurried in water, poured into 75% ethyl ether in petroleum ether (10 ml.), ethyl ether a column 4 . 5 cm. in diameter, packed under a small pres- (60 ml.), and 5%; ethanol in ethyl ether (60 ml.). The sure head of nitrogen to a height of 26 cm. and washed with ethyl ether eluate and the first 20 ml. of the 57' ethanol in water. The bean factor I1 fraction (0.87 g.) from silicic ethyl ether eluate were combined and evaporated to dryness. The oily residue was dissolved in 10 microliters of chloroform acid Chromatography was added in 15 ml. of acetone-water ( 1 : 1) t o the column which was then developed with 50% and transferred to a microcell for the determination of infraacetone in water ( I l.), increasing concentrations of from 60 red absorption spectrum. The methylation of gibberellin to 907' acetone in water (0.8 1.) and acetone (1.4 1.). AI was carried out in a similar manner. Thirty 100-ml. fractions were collected. Evaporation of Acknowledgments.-The authors wish to thank fractions 16-23 yielded 0.07 g. of a pale yellow oil containing bean factor 11. Mrs. Joseph Rogers for technical assistance and also F. Countercurrent Distribution.-The fraction from Frank H. Stodola, Northern Regional Research charcoal chromatography containing bean factor I1 (0.07 g.) was distributed between 10 ml. of the upper phase and Laboratory, U . S . D . A . , Peoria, Ill. for a supply of 10 ml. of the lower phase of a two phase system resulting gibberellin A1 and gibberellic acid, James Merritt from the equilibration of equal volumes of n-butyl alcohol of Merck and Co., Inc., Rahway, New Jersey for and 0.02 JP ammonium hydroxide-ammonium chloride supplies of gibberellic acid and methyl gibberellate, buffer (PH 8). These solutions were introduced into tube 0 of a countercurrent distribution and ninety-nine and Y . Sumiki, Department of Agricultural Chemtransfers were effected in this solvent system. The contents istry, University of Tokyo, Tokyo, Japan for a of tubes 16-40, which showed activity in the d-5 bioassay, supply of gibberellin Az. were acidified to pH 2 with hydrochloric acid (concd.), and the phases were separated. The lower phase was re(28) Skellp Solve B, boiling range GO-8O0. extracted with several portions of n-butyl alcohol. Evapo(29) "Organic Syntheses," Coll. Vol. 11, John W l e y a n d Sons, Inc., (20) Merck reagent grade obtained from Rlerck and Co., R a h w a y , New Jersey. (27) hfodel 2-B, H . 0 Post Scientific I n s t r u m e n t C o , Maspeth, N. Y.
I i e w York, N . Y . , 1963, p. 165. (30) A synthetic adsorbent obtained from Floridin C o . , Tallahassee, Florida.
Los ASGEI.ES, CALIFORSIA
1JOINT COXTRIBUTION FROM THE DEPARTMEST OF CHEWSTRY OF WAYNE STATE UNIVERSITY ASD AGRICOLA,
MINISTERIO DA
THE
INSTITUTO DE QUIMICA
AGRICULTURA, R I O DE JANEIRO]
Naturally Occurring Oxygen Heterocyclics.
1V.I The Methylation of Pyronones*
BY DAVIDHERBST, WALTERB. MORS,OTTORICHARD GOTTLIEBAND CARLDJERASSI RECEIVED NOVEMBER 10, 1958 The contradictory reports in the literature on the diazomethane methylation of pyronones are reviewed and it is shown that such treatment of 6-methyl-2,4-pyronone (triacetic lactone) and 6-phenyl-2,4-pyronone leads in each case to a chromatographically separable mixture of the 2-methoxy-y-pyrone and the 4-methoxy-a-pyrone. These results have a bearing on the structures of several naturally occurring pyrories and attention is again directed to the utility of infrared measurements in settling this point.
Recently, we have reported the isolation from different species of rosewood (Aniba species) of (1) P a p e r 111, P . Crabbe, P. R . Leeining a n d C . Djerassi, THIS J O U R N A L8,0 , 5258 (1958). T h e present paper should also be considered P a r t I V in t h e series "Chemistry of Rosewood." For p a r t 111 see ref. 4. (2) T h e work a t W a y n e S t a t e University was supported b y g r a n t number H-2574 from t h e h'ational H e a r t I n s t i t u t e of t h e National I n stitutes of H e a l t h , U. s. Public Health Service, while t h e investigations
anibine (I), 4-rnethoxyparacotoin (11)3 , 4 and 5,6dehydrokavain (111). 4 The skeletal structures were established rigorously by the course of the alkaline degradation, but the alternate isomeric in R i o d e Janeiro received financial aid from t h e Conselho Nacional de Pesquisas, Brazil. (3) W . B. Mors, 0. R . Gottlieb and C . Djerassi, THISJ O U R N A L , 79, 4507 (1967) ( 4 ) 0. R . Gottlieb and W. B. Mors, J . Oug. Chem., 24, 17 (1959).
2425
D. HERBST, W.B. MORS,0. R. GOTTLIEB AND C ~ R DJER.ISSI L
Vol.
s1
arrangement-the 6-substituted-2-methoxy-y-pyrone formulation (1V)-was excluded largely on the basis of the infrared spectrum which exhibited a band a t 5.77 p attributed3 to the lactone ring of 1-111. In addition, in the case of 3,6-dehydrokavain (111) i t was possible to make a direct comparison4 with a synthetic product of undisputed structure. -4few months ago, there appeared a synthesis5of anibine (I) which confirmed our earlier structural assignment, but which suffered from the weakness t h a t the last step involved methylation with diazomethane of 6- (3'-pyridyl)-2,4-pyronone (Vd) and thus could lead either to an 01or y-pyrone. I t is n-ith this latter aspect t h a t the present paper is concerned.
pyrone (1711) being insoluble in ether.'? In fact Borsche and Gerhardt13 assigned the 2-methoxy-ypyrone structure VIId to yangonin by citing-in addition to other evidence-the observation that the substance formed addition compounds with chloroplatinic and other mineral acids. Borsche's synthesis'? of yangonin involved as the last step the methylation of the 2,4-pyronone s'c and isolation of only oize methylation product, identical with yangonin. However Janisze~~~ska-Drabarek'O showed t h a t both isomeric methoxypyrones VIb and VIIb formed complex salts with chloroplatinic acid, thus weakening Borsche's structural evidence based on salt forination. Indeed, in 1934, Borsche's 2-inethoxy-y-pyrone structure \TId for yangonin was shown to be iricorrect'j since repetition of the methylation of s'c led to both possible methyl ethers s'Id and VIId, of which thc former proved R 4 0 b 0 R-L~-OCH~ to be identical with yangonin. In the light of these results which finally seemed I, R = 3-pj-rid>-l I\' to settle the methylation of 2,4-pyrononesj i t is 11, 3,1-(CHaO? G H e 111, R = CGH~CH=CHsurprising that IViley and Jarboe16 reopened the 4-Methoxy-a-pyrones (VIb,c) and 2-niethoxy-y- question by stating t h a t they were unable to pyrones (VIIb,c) are the respective methyl enol repeat the work of the Polish group,'O t h a t only ethers of the two tautomeric forms VIa and VIIa one isomer (1n.p. 89') was formed in the methylaof the parent 2,4-pyronone (Va,b). In spite of tion of triacetic lactone and t h a t this isomer was extensive work carried out in this area, the course admixed with unreacted triacetic lactone. The of the diazoinethane methylation of such 2,1- methylation product, even though forming a hypyronones (V) is still the subject of considerable drochloride, was assigned the 4-methoxy-a-pyrone structure VIb on the basis of infrared evidence. controversy. No explanation was offered for this discrepancy The earlier literature on the methylation of 6and no reference was made methyl-2,4-pyronone (triacetic lactone) (Va)6 has with the earlier to the important ultra\violet spectral data of the been reviewed by Arndt and Eistert7 who favored the 6-methyl-4-methoxy-a-pyrone (VIb) structure Polish investigators. Since this confusing situation had a very direct for the diazomethane methylation product of triacetic lactone (Ira), which in turn was identical bearing on the structures of the inethoxylated with the product derked from the interaction of pyrones isolated by US,^,^ i t was decided to resolve this question once and for all. Consequently, the silver salt of ITawith methyl iodide. In a subsequent article, Arndt and .%van* the methylation of &inethyl-2,4-pyronone (triemphasized t h a t treatment of triacetic lactone acetic lactone) (17aj in ether solution with diazo(Va) yields only one product (m.p. 86-87') which methane was repeated and the total reaction mixwas now assigned the alternate 6-methyl-2- ture was subjected to chromatographic separation methoxy-y-pyrone (VIIb) expression because of the rather than using the equivocal method of salt formation of a hydrochloride. Shortly thereafter, formation. IVithout any difficulty, there was oba group of Polish worker^^,^^ re-examined this tained a sharp separation which led to G4Yc of diazomethane methylation in detail and con- ~i-methyl-4-methoxy-cu-pyrone (VIb) (ni.1). S(i.5cluded t h a t 6-methyl-4-inethoxy-a-pyrone (VIb) S7.5") and 19% of (j-,ietliyl-2-methoxy-y-pyronc ( i Z % yield, m.p. 88-89',":',:A 280 mp) as ~ c l l (VIIb) (m.p. 94--!11.3"). The physical constants as 6-methyl-2-inethoxy-y-pyrone (VIIb) (2070 and ultraviolet spectra were in excellent agreement 240 mp) are produced with the values reported by the Polish investigayield, m.p. 92-94', X,",riiH , ' ~ there remains no question of the corin this reaction. The separation of the two iso- t o r ~ ~and rectness of their results. mers VIb and VIIb was accomplished by taking Encouraged by this facile chromatographic advantage of the fact t h a t y-pyrones form pyroxonium salts,'' the hydrochloride of the 2-methoxy-y- separation of the two isomers, we directed our attention toward the methylation of 6-phenyl-2,4( 5 ) E. Ziegler a n d E . Nolken, Mo?zalsh., 8 9 , 391 (1958). h-o direct pyronone (Vb). This substance has been syncomparison between n a t u r a l a n d synthetic anibine is reported i n this thesized by several r o ~ t e s ~ and ~ . ' its ~ methylation paper but t h i s h a s since been carried o u t i n Prof. Ziegler's laboratory has been under various conditions, inn i t h a sample sent b y us, t h u s establishing conclusively t h e identity of t h e two specimens, see E. Ziegler, E. S o l k e n and H. Bayzer, ibid., cluding treatment with diazomethane. I n each
ZH3
4
89, 711) (1958). ( ( 3 ) For pertinent references on triacetic lactone see (a) J. Collie, J . Chcm. S o c . , 59, bo9 (1891); (b) F. b r n d t , B. E i s t e r t , H. Scholz a n d E . .4ron, Be?., 69, 2373 (193G); (c) J. A . Berson, THIS JOURNAL, 74, 5172 (1952). ( 7 ) F. A r n d t a n d €3. E i s t e r t , Bev., 68, 1572 (1935). (8) F. A r n d t a n d S . A v a n , i b i d . , 64, 343 (1951). (9) I. Chmiele>\-skaand J. CieSlak, P r z c m g d Chent., 8 , 196 (1952). Janisie,vska-Drabnrek, R o r z ~ i k C i h e w , 27, 456 (3933). J S Collie and '1. Tickle, J . C i i e i i i . Soc , 710 11899).
( 1 2 ) J. Ciellak, Rocznibi Chem., 2 6 , 483 (1952). (13) W ,Borsche and 11,Gerhardt, Ber., 47, 2902 (1914). (14) W ,Borsche a n d C. K. Rodenstein, ibid., 62, 2615 (1929). (15) (a) I. Chmielewska a n d J. CieSlak, Roczniki Chem., 28, 38 (1954); (b) I . Chmielen.ska, J. CieBlak, K . Gorczynska, B. K o n t n i k a n d K. Pitakowska, Tetvahedvon, 4 , 36 (1958). (16) R H. JViley and C. H. Jarboe, THISJ O U R N A L ,7 8 , 624 (1956). (17) I i Ralenkovic and D . S u n k o , Monotsh.,79, l(1948); E. Ziegler a n d H. J u n e k , iDid., 8 9 , 323 (1958).
May 20, 1958
THEMETHYLATION OF PYRONONGS
case, only one isomer was encountered and this was considered'O to be 6-phenyl-4-1nethoxy-apyrone (VIc). Upon repeating this reaction but employing the chromatographic technique mentioned above, there was isolated as the major product 6-phenyl-4-methoxy-a-pyrone (VIc) but in addition there was isolated a small amount of 6-phenyl-2-methoxy-y-pyrone (VIIc). As far as differentiating the a-(VI) and y-(VI1)pyrone isomers is concerned, ultraviolet spectral evidence of the type employed by the Polish workersg is satisfactory, provided no additional chromophore is present. I n the 6-methyl series (Va) , the 4-methoxy-a-pyrone(VIb) exhibited h,E,',O,''280 r n p (log E 3.80), while the 2-methoxy-ypyrone showed XEt,"," 240 mp (log E 4.13). However with additional chromophoric substituents a t C-G, as was the case with the naturally occurring a-pyrones I, 113and 1114,ultraviolet data cannot be used very effectively in the absence of the other isomer. When both isomers are available, then the one with the longer wave length maximum represents the a-pyrone derivative and this is exemplified with 6-phenyl-4-methoxy-a-pyrone(VI c) ",":A(: 314 mp, log E 4.13) as compared t o 6phenyl-2-methoxy-y-pyrone (VIIc) (AZO," 276 mp, log E 4.29). Wiley a n d JarboeI6 pointed out t h a t a-pyrones show an infrared carbonyl band near 5.8 p, while the first carbonyl band in 2-hydroxymethyl-5hydroxy-6- (a-hydroxypropiony1)- y-pyrone does not appear until close to 6.0 p.15b,19 It was on this basis that these authors attributed (correctly) the 6methyl-4-methoxy-a-pyrone (VIb) structure to the single product isolated b y them in the methylation of triacetic lactone (Va). I n view of the confusion in the earlier literature and the recent importance of methoxylated 2,4-pyronones among natural products, we have summarized the relevant infrared carbonyl absorption data in Table I. Since these include two pairs of isomeric methoxylated a- and y-pyrones (VIb,c and VIIb,c), there exists no question t h a t the infrared spectral evidence can be used as a secure criterion for differentiating between the possible tautomeric forms of 2,4-pyronones and between their respective methylation products-the y-pyrone derivatives (VII) exhibiting their first carbonyl band near 6.0 p , while apyrones absorb near 5.80 p (somewhat variable detypical of pending upon the solvent; see Table I),2o unsaturated six-membered lactones. Attention has been calledI6 to the fact that the infrared spectrum (potassium bromide pellet) of triacetic lactone (Va) contains a strong band a t 5.8 p , indicating t h a t the substance exists largely as the a-pyrone tautomer VIa. It is interesting to note t h a t in our hands the corresponding 6-phenyl analog Vb appears t o exist largely as the y-pyrone ~
(18) Here, as well as with 6-methyl-2-methoxy-y-pyrone (VIIb) -the preparation of which was questioned (ref. iG)-direct infrared comparison with specimens kindly provided by Dr. S. JaniszewskaDrabarek (University of Warsaw) confirmed the identity with her samples (ref. 10). (19) L.L. Woods, THISJOURNAL, 7 7 , 3161 (lQ55). ( 2 0 ) I t should be emphasized that this refers only t o the first absorption band in the carbonyl region. All 4-methoxylated-a-pyrones listed in Table I also show an intense band near 6.05 f i , which has been assigned (ref. 3) t o the enol ether grouping.
2429
TABLE I ISFRAREDABSORPTIOXDATAOF METHOXYLATED PYROSES First
First
co
CO band,
I-Methoxy-~-pyrones fi 6-Methyl-4-methoxy-a- 5 8 5 O pyrone (VIb) 6-PhenyM-methoxy-apyrone (VIc) 5 86' 4-Methoxyparacotoin (11) 5 75br3 Anibine (I) 5.77"*3 5,G-Dehydrokavain (111) 5 84' Yangonin (Vld) 5 85"
2-Methoxy-y-pyronesc 6-Methyl-2-methoxy-ypyrone (VIIb) 6-Phenyl-Z-methoxy-ypyrone (VIIc)
band, ~r
5 98' 5 97"
Chloroform solution. Nujol mull. Three nonmethoxylated y-pyrones were also measured a t the same time: maltol 6.04 p ) , kojic acid":::A( 5.99 p ) and pyrorneconic acid ( 6.04 p ) .
tautomer VIIa in the solid state. However in ethanol solution, the predominant tautomer is the 4-hydroxy-a-pyrone (VIa) , since its ultraviolet absorption maximum a t 317 mp closely resembles that (314 mp) of the methyl ether VIc. I n conclusion i t can be stated (a) t h a t methylation of 2,4-pyronones with diazomethane usually yields mixtures of the two possible isomers, the actual proportions depending on the nature of other substituents; (b) t h a t spectral evidence can be used to good advantage in differentiating between the two possible enol ethers; and (c) t h a t all methylated 2,4-pyronones which have so far been encountered in nature are 4-methoxy-a-pyrones. 0
Va, R = b, R = C, R = d, R =
OR'
0
CH3 CfiHj P-CHzOGHdCH=CH3'-pyridyl YIa. R = CH, or CRH, b , R = R' = CHI C , R = CtiHj; R ' = CH3 d, R P-CHaOCtiHdCH=CHR' = CH3 YIIa. R = CHI or C6H5 'R'= H b. R R' e CH, C , R = CsHs; R ' = CHI d, R = P-CHZOCsHdCH=CHR' = CH3 E
Experimental2 Methylation of 6-Methyl-Z,4-pyronone (Triacetic LacJone) (Va).-Triacetic lactone (1.26 g., m.p. 188-189 , recrystallized from acetonitrile) was treated at room temperature with an ethereal solution of diazomethane prepared** from 21.5 g. of p-tolylsulfonylmethylnitrosamide. All solid dissolved within 15 minutes and after 6 hr. at room temperature, the mixture was left a t 10' for an additional 16 hr. and was then evaporated t o dryness in z'acuo. The resulting sticky solid (1.58 g., m.p. 55-65') dissolved in 7 cc. of benzene was placed on a column of 50 g. of Xlcoa grade F-20 alumina (deactivated by shaking in hexane suspension with 1.5 cc. of 10% aqueous acetic acid). Elution with 1: 1 hexane-benzene, pure benzene and 1: 1 benzeneether furnished 0.90 g. (64%) of 6-methyl-l-methoxy-a(21) Melting points were determined on the Kofler block. We are indebted t o Dr. H. Kovacs and Miss B . Bach for the infrared measurements and t o Mr. K . Hutchinson for the ultraviolet absorption spectra. Several of the spectral measurements were obtained through the courtesy of Dr. J hl. Vandenbelt and associates of Parke, Davis and C o . (22) T. J. DeBoer and H. J. Backer, Oug. Synlheses, 36, 16 (1956).
pyrone (VIb), 1n.p. 81-86'; two recrystallizations from 0.15 cc. of water. T h e solid, obtained upon pouring into ice-water, was collected and washed with cold water and cyclohexane yielded 0.62 g. of pure material, m . p . 86.587.5', 280 m p (log E 3.80), A"_:* 238 mp (log E 2.96); then carbon tetrachloride in order t o remove benzoic acid. rlfter drying, the cream-colored solid (0.67 g., m . p . 23%A%? 5.85(s), 6.05(in) and 7.94(s) p . Further elution of the column with 1: 1 ether-ethanol led 241' dec.) was recrlstallized from methyl ethyl ketone whereuuon it exhibited m.D. 235-236' (dec.: variable det o 0.27 g. (19yi) of slightly )-ellowish crystals ( m . p . 91-93') 317 nip (log E 4.11), of 6-methyl-2-methoxy-~-pyrone (VIIb); this material was pending upon rate of heating), obtained in a colorless state (0.17 g.) after two recrystalli- ' .:;A: 6.10(s) and 7.90(s) p zations from cyclohexane and exhibited m . p . 94-94.5', .4nnZ. Calcd. for C I I H S 0 3 :C, 70.21; 11, 4.29. F o u n t l : X 2:" 240 nip (loge4.13); hSi121,C'5.98(s), 3 6.17(m) and 7.92(s) C , 70.50;H, 4.40. p. These physical and spectral constants are in excellent The methylation of 0.57 g. of G-pheiiyl-2,4-pyro1lone was :igreelnent with those recorded in the literature.g~lO~ls performed exactly as described above for triacetic lactone l\%en the inethylation was conducted a t 0-5" exactly a s except t h a t t h e reaction mixture W:LS left a t room temperadescribed bk- U'iley and Jarboe16 and the mixture processed ture for 16 hr. Chromatography of the total reaction prod3s above by clironiatography, there W:LS isolated 52% of 6- uct (1n.p. 11%-12Io) on 20 g. of dlcoa grade F-20 alumina 1 n e t h y l - 1 - r n e t I i ~ ~ x y - ~ - p y r ~(YIb) ~ r 1 e (t1i.p. 80-8-Io, raised (deactivated with 0.6 cc. of l(J5; aqueous acetic acid) and t o m . p . 87-88' after one recrystallization), and 8y0 of 6- elution with benzene gave 0.33 g. of 6-phenyl4-methoxy-oInetliyl-2-nietlioxy-~,-pyroiie ( V I I b ) (m.p. 89-93", raised t o pyrone (VIc), ti1.p. 123-132', raised t o m . p . 129.5-131 .5°18 91-93' after one recr tallization). Identity of these prod- upon further recrystallization from cyclohexane; ":!A: 311 ucts with the ones is0 ted in the rooin temperature methyla- inp (log E 4.13); 5.86(s), G.lO(s) and 6.40(s) p ) . tion experiment was established by mixture melting point A n d . Calcd. for C1,HloO.j: C, 71.28; H , 1.98; 0, determination and by coincidence of the relevant infrared 23.T4; OCHD, 15.35. Found: C, 71.12; H , 5.OX; 0 , and ultraviolet absorption spectra. Methylation of 6-Phenyl-2,4-pyronone (Vb).--4 mixture 23.56; OCH,, lc?.13. of 8.0 g. of ethyl benzoylacetate,
