Nov., 1950
5-KETO-7-METHYLJULOLINE AND CERTAIN DERIVATIVES [CONTRIBUTION FROM THE
CHRMISTRY
4989
LABORATORY OF DEPAUW UNIVERSITY]
5-Keto-7-methyljuloline and Certain Derivatives BY D. J. COOK,DARRELDOCKAND ROBERT SHRONTZ’ Since Reissert first prepared 5-keto-7-methyl- reaction. Condensation reactions between nitroj ~ l o l i n eby ~ ~the ~ action of ethyl acetoacetate on methane and nitroethane with I1 gave the two (IV) tetrahydroquinoline, no further work has been products, a-(5-keto-7-juloline)-/3-nitroethanol reported on this type compound. Several studies and cr-(5-keto-7-juloline)-/3-nitropropanol(V). have been reported concerning the analogous The aldehyde was also reduced to the corresponding 5-keto-7-julolinemethanol (VI) with aluminum compounds, N-sub~tituted-4-methylcarbostyrils.~*~ The use of the same techniques and ideas have i-propoxide and this compound converted to the been found applicable to the investigation of the 5-keto-7-chloromethyljuloline (VII) with thionyl chemistrv of 5-keto-7-methyljuloline. chloride. Oxidation of I1 with acid sodium diIn a iecent article6 CHARTI the preparation of 3keto -7- methyljuloline and its conversion to 7 -formyl - 5- ketojuloline by oxidation with selenium dioxide have already been reported. The study has now been extended to the preparation of a number of derivatives of 5-ketojuloline substituted in the 7 position. The series of reactions stem from 5 keto -7-methyljuloline (I) which is indicated in Chart I. The system of numbering is indicated for the juloline ring system. The methyl group in the 7 position has been found to be activated in a manner similar to the 4-methyl group in N-substituted-4-methylcarbostyrils. This should be expected from the similarity in CHz structure of the two CHzC1 I 1 molecules. Therefore, C=N VI1 -NOH when I was treated I with selenium dioxide XI1 COOH XI in a fusion reaction. the methyl group was oxidized to the aldehyde chromate gave 3-keto-7-juloline carboxylic acid (11) in yields of 80%. This compound, 7-formyl- (VIII). 5-ketojuloline, was converted t o 7-(5-ketojulo- A Claisen type condensation was accomplished line)-phenylmethanol (111) by treatment with when I was treated with diethyl oxalate in the phenylmagnesium bromide in the usual Grignard presence of potassium ethoxide and subsequently acidified. The resulting product was ethyl 7-(5(1) Department of Chemistry, F’urdue University, Lafayette, ketojuloline) -pyruvate (IX) This compound Indiana. with hydroxylamine hydrochloride gave the (2) ReiBcr.. 14, 841 (1891). (3) Reissat, ibid., 16, 108 (1892). corresponding oximino ester (X) and the oximino (4) Kaplow and Cook:,THIS JOUEXAL. 6’1, 1960 (1045). acid (XI) was obtained when X was treated with (5) Cook and Stamper, ibid., BB, 1467 (1947). an alcoholic 2 N sodium hydroxide solution. 5(6) Cook, Sears and Dock, Proc. Indiana Acad. Sci., W, 146 Keto-7-julolineacetonitrile (XII) was formed when (1948).
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4990
I). J. COOK,DARREL DOCKAND ROBERT SHRONTZ
Vol. 72
Anal. Calcd. for C1aHFpONCl: Pi, 6.00. Found: E, 5.95. 5-Keto-7-juloliiecarboxylic Acid (VIII) .-Three grams of 7-formyl-5-ketojuloline (0.014 mole) was suspended in 150 ml. of water to which was added 2.1 g. (0.007 mole) of potassium dichromate. This mixture was stirred and over a period of five minutes 7.1 ml. of concd. sulfuric acid The necessary starting materials, 5-keto-7-methyljuloline (I), 7-formyl-5-ketojuloline (11) and selenium was added. The reaction mass was heated for about twenty minutes m
