YOLANDA T. PRATT WITH XATHAN L. DRAKE
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nitrobenzene-petroleum ether, v as sublimed at bath temperature 145' (0.08 mm ), t o give pure m-nitrophenylpyruvic acid, m.p. 158-159', sintering at 152". m-Xitrophenylpyruvic acid exhibits an intense green ferric chloride color test. A?zal. Calcd. for C9HiOjS: C, 51.68; H, 3.37; S, 6.71. Found: C, 51.98; H, 3.69; h', 7.06. m-Sitrophenylpyruvic acid, 35 mg., was dissolved in 350 mg. of concentrated sulfuric acid and heated on the steambath for 1.5 hours, b y which time the solution was dark brown and gas evolution had ceased. Eight cc. of water was added to the cooled solution, the suspension centrifuged, and the filtrate estracted with ether. Evaporation uf the ether extract left 15 mg. o f crystalline ycllow residue; twi.) recrystallizations from water brought the m.p. to 116-117"; mixed m.p. with authentic In-nitrophenylacetic acid, synthesized by the method of Gabriel and Borgmann'e showed no depression. (16) S. Gabriel and 0. Burgmann. h'r;
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1 6 , 2065 11x83)
[CONTRIBUTION F R O M
Quinolinequinones.
THE
Yol. 77
Dehydration of threo-Methyl P-PhenylglycerateIi with Sulfuric Acid.-A solution of 0.190 g. of threo-methyl 0phenylglycerate and 0.35 g. of concentrated sulfuric acid u-as heated for 3 minutes on the steam-bath, a t the erid o f which time the color was dark brown. On adding ice-water and cooling, a red oil appeared which was extracted xith ether. Extraction of the ether solution Kith aqueous sodium bicarbonate three times, followed by acidificatiol! of the combined bicarbonate extracts, deposited an amorphous mass. This was distilled (short path, 120" (02 m m . ) ) and recrystallized from benzene. The colorless phenylpyruvic acid melted a t 156-157' with decomposition; estimated yield was 15yo. Literature values are giveii variously as 154-155", 156' and 159-160".1s The acitl gives a strong green color with acidic ferric chloride. _____ (li) K. Ruber, ibid., 6 4 , 1960 (1921); R. P. Linstead, L. K ,Owen and R . F. Webb, J . C h e m . Suc., 1218 (1953). (18) C . Granacher, Helr. Chim. Acta. 6 , 613 (1922).
NEW HAVEX,CONS
DEPARTMEST O F CHEMISTRT, c K I V E R S I T P O F I f A R Y L A S D ]
111. Derivatives of 6-Hydroxy-5,8-quinolinequinone
BY YOLXNDA T. PRATT WITH XATHAN L. DRAKE RECEIVED MARCH24, 1955 7-Alkyl-6-h~-drosy-5,8-quiriolinequinoneshave been prepared by the alkylatioii of G-h~drox~-5,8-quinolinequinorie (I) \sith diacyl peroxides and these products have been coiiverted, by means of Hooker oxidation, t o 6-alkyl-7-hydroxy-5,Xhave been obquinolinequinones with one less carbon iii the side-chain. 7-8minomethyl-6-h~-droxy-5,~-quinolinequinones tained by trexting 6-hydroxy-5,X-quinoli1iequinone( I ) with formaldehyde and a primary or secondary amine.
Xumerous biologically active compounds have peroxides was used. The yield of the propyl derivbeen prepared from 2-hydroxy-l,4-naphthoyuinone ative6a I1 was somewhat lower (18%),and that of the by the introduction of side-chains a t the :%position. undecyl derivative I V was higher (11%) than those The 3-alkvl derivatives obtained by the action of reported for the corresponding naphthoquinones. diacyl peroxides on the parent compound' or by The undecyl derivative I P is not only related to Hooker oxidation of the next higher &alkyl homo- the naphthoquinone antimalarials but contains the log3are active as antimalarials ; the 3-aminomethyl side-chain of embelin, a dihydroxybenzoquinone derivatives, synthesized by means of the Mannich derivative which is reportedly an anthelmintic.? r e a ~ t i o nhave , ~ been patented as parasiticides. In TABLE I the present work, the application of these three reDERIVATIVES 3F 5,8-QLiIXOLIYEQUINOXE actions to the analogous 6-hydroxy-5,8-quinolineY:eld Carbon Ct Hydrogen lI.P..U quinone5,6 (I) (6-hydroxy-5,8-dihydroquinolinedi-Cmpd ac. Calcd Foundb Calcd Found!> one) has been investigated in the hope that pharmaI1 151 0-152.3 Iti 66 35 66 56 3 11 5 13 cological tests on representative examples of the re3'4' A7 32 ti7 64 5 67 5 57 111 131 0-135 0 sulting products will furnish clues as to the most 91 5-92.5 44 7 2 91 72 77 8 26 8 01 IV promising types of derivatives for further studies. 1203.8-206.0" K' 66 02 65 25 1 47 4 -The alkylation of I with diacyl peroxides was car138.0-139.0 1 3 66 35 86 59 5 11 1 8 8 1.1 ried out according to the method of Fieser, Leffler 72 35 i2 27 7 9'4 8 0 1 VI1 110.0-111 .I) fi8 and co-workers2b except that a 10% excess of the 61 60 (54 47 6 20 A 2.5 VI11 167.0-168, 5'2 81 ( 1 ) This investigation was supported by a research grant ( P H S B-665) from t h e National Microbiological Institute of t h e National Institutes of Health, Public Health Service. ( 2 ) ( a ) I , . F . Fieser and A. E. Oxford, THISJ O U R N A L , 64, 2060 (194'2); i b ) 1. F . Fieser, M. T. Leffler, et o l . , ibid., 70, 8174 (19481. ,':+) ( a ) S. C Hooker. i b i d . , 68, 1163-1179 ( 1 9 3 8 ) : (h) I.. F. Fieser a n d X I . Fieser, ibid., 70, 3215 ( 1 9 4 8 ) . (1: 11.T Lemer and R. J. Hathaway. ibid.. 70, ,3222 (19481; X I . T . 1.efiIer. U. 5 Patent 2,541,473 (1951) [C. A , , 46, 7149f (1'25l)l. Y 'I. Pratt with X L. Drake, T H I S JOURNAL, 77, 37 (195.5) I n related studies of t h e mode of addition of various reagents tu i.8-riuinolinequinone, we have found t h a t 5.6.8-triacetoxyquinoline may he isolated in 47% yield after t h e addition of acetic anhydride fThiele reaction; J. Thiele and E. Winter, An?i., 311, 347 (1900); L . F. Fieser, THISJ O U R N A L , 70, 3165 (1948)). This triacetoxyquinoline may be converted t o I by methods used for t h e analogous conversion in t h e naphthoquinone series (L. F . Fieser, loc. L i t . ) . Since 5,Equinolinequinone i \ obtained from t h e readily available &-hydroxy v > d e \ suitahle altrr1iatii.r Y \ t i l hr5i.: f l > - b e
