1190
SAMUEL C. HOOKER
the compounds of the iomatiol series undergo and of their relationship to substances of the lapachol series. The transformations described in this paper include the conversion of lomatiol into lapachol through a series of intermediate sub-
Vol. 68
stances, and since one of these can be prepared also from synthetic isolapachol, the work reported constitutes a synthesis of lapachol. 82 REMsEN STREET BROOKLYN, N.Y.
RECEIVEDAPRIL3, 1936
The Constitution of Lapachol and its Derivatives. Part V, The Structure of Patemb’s “ Iso1apiehone”1~2 BY SAMUEL C. HOOKER “Isolapachone” was first referred to by Paterna3
In the course of the study of the action of concentrated sulfuric acid upon lornatiol, the discovery by RennieBof a compound isomeric with two acetyl groups, followed by spontaneous oxi- and in some respects similar to Paternb’s “isodation, from a compound formed by the action of lapachone” gave rise to uncertainties and errors acetic anhydride and sodium acetate upon lapa- of interpretation both as to its own structure and chol. Seven years later the compound was that of “isolapachone.”g This was mainly due to studied by Paternb and Minunni4 and the con- misconceptions regarding the structure of lomaclusion reached that the substance is similar to tiol. In a recent paperm evidence has been preand isomeric with lapachone (p), the compound sented which fully establishes the structure of resulting from the action of concentrated sulfuric lomatiol, and in the course of this work it was acid on lapachol. This view was shown by me to shown that Rennie’s compound has the formula be untenabk,b for in investigations published in I and can be regarded as a dehydroiso-&lapa1892 it was found that the so-called “isolapa- chone. An isomeric dehydro derivative of iso-pchone” and also the diacetyl compound from which lapchone was obtained in an earlier investigait had been obtained had each two atoms of hy- tion’ both from lapachol and by synthesis and drogen less than required by the formulas assigned by Paternb and Minunni. At that time I suggested a structural formula for the diacetyl comV V \ O pound which twenty-three years later received ll additional support from the experiments of L. 0 (1) 0 (11) Rennie’s Compound Isopropylfurano-1,2-wphM0nti.B The matter was discussed by Monti thoquinone apparently in ignorance of the revised and now generally accepted formula7 for lapachol which it was assigned the structure If. The correspondnecessitated a corresponding modification in “iso- ing para quinone was also fully characterized. I n lapachone” and all the compounds derived from this paper it will be shown that the preponderance of the facts now known favors formula 111, lapacbol studied previous to 1896. or possibly IV, for “isolapachone.” The equiva(1) See Editor’snote (I),THISJOURNAL,68, 1163 (1936) (2) Dr. Hooker wrote a preliminary version of the iwtroduemy leet of formula IV, based upon what was then part of this paper in April, 1931,but he did not find time subsequently
in 1882 in his “Ricerche sull’acido lapacico” (lapachol). It was obtained by the removal of
to incorporate in the manuscript certain modified views and new interpretations growing out of his more recent work on this and related problems I was informed of his views throughout this period, however, througb correspondence and conversations, and from the letters and from the notes of his assistant Dr A Steyermark, I have been able to revise a e paper in accordance with Dr Hooker’s wishes and in large part in his own words The experiments recorded were carried out with the collaboration of Mr. H. W. Shepard and Mr. J. G Walsh, Jr , in 1891-1896, and of Dr G H. Connitt and Dr A Steyermark in the more recent period -L. F. FIESER. (3) Paternb, Garr chrm. h l , U,337 (1882). (4) Paternb and Minunni, rbrd , 19, 607 (188‘)) ( 5 ) Hooker, J Chem S o c , 61, 611 (1892) , ( 6 ) Monti, Gam chrm rfal , 46, 11, 58 (191n) (7) Hcwkrr, J Chem Vnr , 68, 1:LM (1ROA)
0
0 (111) 6 W) believed to be the structure of lapachol, was previously suggested by me5 but afterward aban(8) Renuie, ibid , 67, 786, 792 (1845) (9) Hooker, ibrd , 69, 1362, 1370, 1377, 1382 (1896) (10) f h l k e r ’1 HILI r O l J R N A 1 , 68, 1181 (1Y.36)
THESTRUCTURE OF PATERNb’S “ISOLAPACHONE”
July, 1936
donedo for the reasons stated above, the cornpound thereafter being referred to as pseudodehydrolapashone. On the basis of the present work the name dehydrolapachone may be assigned to the compound. When lapachol is submitted to the action of mineral acids it can be converted quantitatively into either a-lapachone or 8-lapachone according 0
0
(V) a-Lapachone 0
/I 0
1191
I have since converted into IX the isomeric diacetyl compound which H. W. Shepard working in my laboratory observed was simultaneously formed when following Paterna’s directions for the preparation of the diacetyl compound which he described. Shepard’s experiments, mentioned briefly in an earlier communication,6 are recorded in detail in the experimental part of the present paper. The second diacetyl compound was possibly overlooked by Paterna and by Monti on account of the melting points of both derivatives being almost identical. These compounds ran, however, be readily distinguished by their color reactions with concentrated sulfuric acid. It is evident from the results of the hydrogenations that the isomeric diacetyl compounds must bear the relations to a- and 8-lapachone, respectively, which the formulas X and X I indicate. OCOCHs
CHI
(VI)
(yJCH*“
