&lay, 1946
REACTION BETWEEN
BROMOTRIMETHYLQUINONE AND SOD10 MALONIC ESTERS
Summary The preparation of seven new basically-substituted isoalloxazine compounds and the intermedi-
887
ates used in their preparation has been described.
sTATE cOLLECE, pENNskLVANIA
RECEIVED J A N U A R26, Y 1946
[CUNTRIBUTION FROM THE SCHOOL OF CHEMISTRY O F THE UNIVERSITY OF MINNESOTA]
The Reaction between Quinones and Metallic Enolates. XX.l Second Paper on Bromotrimethylquinone and Sodio Malonic Esters BY LEE IRVIN SMITH AND PAULF. WILEY~ The reaction between methylated quinones and metallic enolates, leading to coumarins, has been pictured as involving four steps: (a) a “pentadenolization” oi the quinone to give a methylene quinone, such as I ; (b) a Michael reaction, involving addition of the metallic enolate (or of its ions) t o the new conjugated system in I, producing the hydroquinone 11; (c) cyclization of I1 t o a hydrocoumarin 111; and (d) dehydrogenation of the hydrocoumarin to the coumarin V. The end result of this series of reactions will depend upon a number of factors such as the relative velocities of competitive (or consecutive) reactions, solubilities of the intermediates, oxidizing power of the quinone (or its tautomer), presence or absence of air or other oxidizing agent, etc. Theoretically i t is possible, therefore, for the reaction between a methylated quinone and a metallic enolate t o produce either a coumarin or a hydrocoumarin. Although the products have been coumarins in all cases heretofore observed, it has now been found that the reaction between bromotrimethylquinone and methyl malonate in the presence of magnesium methoxide produced not the coumarin V, but the hydrocoumarin 111. 0
/I
H ~ C ~ = = C H ~ H&()13r OH
I
OH
I1
?&OJ=o Br
I11
H \ /COOCHI R“ I V , R‘ = Br, R * = CHS V , R’ = CHs, R@ = Br
The product of this reaction (obtained in a yield of S9yo) formed a diacetate and gave a dimethyl ether by reaction with diazomethane, which eliminated structure V for it. The presence of an ester grouping in I11 was shown by hydrolysis of the substance to carbon dioxide and (1) Paper XIX.Tms JOURNAL, 66, 1320 (1944). (2) Abstracted from a thesis by Paul F. Wiley, presented t o the 1;raduate Faculty of the University of Minnesota, in partial fulfilment of the requirements for the Ph.D. degree, J u l y , 1944.
a non-acidic substance VI, although the properties of VI were somewhat peculiar for a compound of this structure. It was not possible to convert I11 into VI1 by action of potassium hydroxide and methyl sulfate according to the method of Smith atld Denyes.a Since the condensation between CHI H&f)/O\FO
OCHI H~C&~CH~CHZCOOH
H QBrJ
H&()Br OCHs
VI
VI1 0
/I
H~C~~CH~CH(COOCH~),
H3Cvr 0 VI11
alkylated quinones and metallic enolates, leading to coumarins, involves dehydrogenation a t some step, it appeared possible that I11 could be dehydrogenated to V. This reaction was achieved. When I11 was refluxed with trimethylbromoquinone in methanol or dioxane, V was formed in a yield of 20770; in the first case, trimethylbromohydroquinone was isolated from the reaction mixture. The product V, as well as its acetate, was identified by comparison with authentic samples. I n previous papers4 reports have been made of successful dehydrogenations of dihydrocoumarins by action of ferric chloride. When the hydrocoumarin I11 was subjected to the action of ferric chloride in methanol, the quinone VI11 was formed in a yield of 90%. This quinone was reduced readily to the hydroquinone 11, which on oxidation regenerated VIII. The hydrocluinone 11,when hydrolyzed by action of hydrochloric acid, gave the same substance VI as was obtained by similar hydrolysis of the hydrocoumarin 111. This indirect conversion of I11 to VI Via VI11 and I1 afforded added evidence that the substance was not a coumarin, V, and i t also eliminated I1 as a possible structure for this product (the com(3) Smith and Denyes, THISJOURNAL, 68, 304 (1936). (4) (a) Smith and Horner, THISJOURNAL, 60, 676 (1938); (b) Smith and Johnson, i b i d . , 69, 673 (1937).
888
LEE IRVIN SMITH AND PAULF. WILEY
Vol. 68
positions of I11 and 11, as well as of their derivatives, are nearly the same). Granted that structure I11 is correct, then the diacetate and dimethyl ether of this substance must be derived from the enolic form of 111 and must be represented by IX and X, respectively.
of ether), the difference between the products in the two cases must be due to differences in the relative rates of the competing reactions. With regard to the last two steps, cyclization atid dehydrogenation, i t cannot be said with certainty which occurs first. What evidence there is, however, indicates that cyclization precedes dehydrogenation, for i t has been possible to dehydrogenate the hydrocoumarin TI1 to the coumarin V by action of a quinone, whereas no such dehydrogenation of benzylmalonic esters Br such as I1 to benzalmalonic esters has been obIX, R = CHiCO XI, R’ = Br, R ” = CH1 served. X, R = CH, XII, R’ =CHs. R ” = Br Coumarin IV was prepared not only from the benzyl chloride XI, but also from the aldehyde XITI. This coumarin, however, was not identical with the carbomethoxycoumarin previously reH3C R@o \OH ported4b as obtained from trimethylbromoquinone. Nor was the carbethoxycoumarin synXIII, R’ = Br, R“ = CHs XIV, R’ = CHa, R ” = Br thesized from XI identical with the carbethoxyNo compounds of this sort are known, although coumarin previously reported4b as obtained from several enol derivatives of analogous five mem- triniethylbromoquinone and sodio ethyl malonate. Therefore the structure IV, previously rebered ring structures-isocoumaranones-are ported for these products, is in error. However, known.5 the coumarin V derived from the benzyl chloride The hydrocoumarin VI was a difficult substance to purify, and concordant analytical values could XI1 as well as from the bromoaldehyde XIV and not be obtained for it. Nor could i t be converted methyl malonate was identical in all respects into the quinone propionic acid (corresponding with the corresponding coumarin ester preto VIII) by the method previously used3 for such viously obtained from bromotriniethylquinone transformat.ions of hydrocoumarins. Neverthe- and metallic enolates of malonic esters. It folless, in view of the formation of V I by action of lows that all the basic structures reported by hydrochloric acid upon both I11 and 11, there can Smith and Johnson,4b with meta orientations of the methyl groups, must be replaced by structures be little doubt of the structure of VI. This work provides the first example of a re- analogous to V with ortho orientations of the action between an alkylated quinone and a metal- methyl groups. In order to make certain of the identity of the lic enolate in which the reaction conditions are various specimens of V, and to avoid any error such that a dihydrocoumarin can be isolated. due to a possible failure of the mixed melting From the mother liquors remaining after I11 was point tests, X-ray powder diagrams were deterremoved, there was isolated a very small amount mined of four samples of 3-carbomethoxy-5of a yellow solid melting around 200°, which was bromo-G-hydroxy-7,8-dimethylcoumarin, y. The most likely the coumarin V (m. p. 241°), although four specimens of V were as follows, and the the amount was insufficient for purification and diagrams are shown in Fig. l . 7 It is obvious, identification. That slight changes in conditions, etc., may exert a considerable effect upon the from the diagrams, that all four samples are nature of the product is shown by the fact that identical. In the earlier paper4b it was shown that triwhen the magnesium enolate of ethyl malonate methylbromoquinorie and magnesio ethyl malois used, the main product is the coumarin V. nate reacted to give an excellent yield of a magCoumarins IV and V were formed when the nesium derivative, which was converted by action substituted benzyl chlorides X I and XII, reof hydrochloric acid into the coumarin ester spectively, were used to alkylate sodio methyl corresponding to V. However, this magnesium malonate; a coumarin was also produced when derivative, by action of methyl sulfate or of acetyl X I was used to alkylate sodio ethyl malonate. was converted into products closely rechloride, These results are in contrast to those obtained in a lated to, but different from, the methyl ether and previous study of pseudophenol halides6 which (7) The authors wish t o acknowledge their indebtedness to Dr. gave benzylmalonic esters or hydrocoumarins, Harold P. Klug of this Laboratory, who prepared the diagrams. rather than coumarins. Since the only difference Sample 1 was passed through a 250-mesh sieve; the others were in procedure used in handling these two pseudo- ground, hut not sieved. The samples were mounted as a sheet of phenol halides and the one previously studied6 powder between Scotch tape and were photographed on sextants of a involved a change in the solvent (dioxane in place flat, circular film using Cu-Ka radiation at approximately 30,000 (5) (a1 Smith and Nichols, ibid., 65, 1739 (1943); (b) Wilds, ibid., 64, 1421 (1942); (c) Wilds and Johnson, i b i d . , 67, 2813 (1945). (6) Smith and Carlin, ibid., 64, 524 (1942).
volts and 20 milliamperes. Exposure two hours; distance from sample t o film approximately 5 cm.; 0.025 inch pinhole slits. The sample was oscillated and the camera was rotated a t 1 r.p.m. during the exposure.
May, IN6
REACTION B E T W E E N BROMOTRIMKTHYLQUINONE A N D S O D 1 0 MALONIC ESTERS
s80
acetatc of V (ethyl ester), respectively. These coiiilnnnids were tentatively assigned structures XV a i d XVI. 'rilese substances liave tiuw been
OH
XV.R XVI.I
