6608
-~R.IHAM S.
[CONTRIBUTION FROM
THE
Enzyme Models.
VOl. 77
ENDLBK AND ERXEST I . BECKER
CHEMICAL LABORATORIES O F THE
P O L Y T E C H N I C INSTITUTE OF
BROOKLYN]
IIL1 Synthesis of Some New Oxindole Derivatives
BY ABRAHAMS. ENDLER AKD ERNESTI . B E C K E R ~ RECEIVED J U X E 13, 1955 Several compounds related to 3-aminooxindole have been synthesized via hydantoins derived from ortho-substituted acetophenones. These compounds are of interest as organic catalysts in the decarboxylation of benzoylformic acid. Previous work in this Laboratory' has indicated the probability of a cyclic transition state in the decarboxylation of benzoylformic acid (I) when catalyzed b y 3-aminooxindole 11. 0 fi--&-COOH
H fi----C-SH2
I1
I
I1
'I'hc purpose of this paper is to report the synthesis of a number of compounds designed to test this mechanism. Compounds which would prevent a cycle from occurring are 3- ( a ,a-dimethylbenzylimino)-oxindole (111), and 3-methyl-3-aminooxindole (IV). The kinetic studies will be reported later. CH?
A ---C=S-C-C6Ha I
H 111
I
CHd
p$---L-SH2
The synthesis of 3-benzylideneaminooxindole (X) was reinvestigated. It was found that the tan-colored product obtained according to the previous preparation3 could be purified further by crystallization from pyridine, the pure compound being colorless. Acid hydrolysis of X gave benzaldehyde and I1 as the only products, confirming the structure previously postulated. Alternatively, X was synthesized by direct reaction of I1 with benzaldehyde. Characterization of I1 is rendered more difficult by its ease of oxidation and by the lack of any recorded derivatives with definite melting point. Investigation showed that usual methods of acetylation give a mixture of products which melts over a wide range. Careful acetylation a t room temperature gave a pure monoacetyl derivative. Similarly, a previously unreported acetyl derivative of 1methyl-3-aminooxindole was prepared.
1
H 11-
Experimental4 3-(~t,a-Dimethylbenzylimino)-oxindole(III).--a,a-Di-
The Schiff base, 111, was prepared by reaction of inethylbenzylamine was prepared according to Brander5 by of a,m-dimethylbenzyl chloride with liquid ammonia. isatin with a,a-dimethylbenzylamine without par- reaction Isatin (5.0 g., 34 mmoles) was mixed with 140 g. of oticular difficulty. xylene, 4.5 g. (33 mmoles) of a,a-dimethylbenzylamine, Several routes were attempted in the synthesis of 10 g. of dimethylaniline and 30 g. of n-butyl alcohol. The IV. Nitrosation of 3-methyloxindole, followed by mixture was refluxed for 2 hr. and then concentrated to 75 hydrogenation, gave only resinous material. Simi- ml. On cooling, 5.8 g. of orange crystals was obtained. These were ground for 5 min. with cold 5% sodium hydroxlarly, treatment of 3-methyl-3-hydroxyoxindole ide solution (to remove unchanged isatin) and then immewith hydrochloric acid or thionyl chloride, followed diately filtered, washed with cold water, and vacuum dried by reaction with ammonia, gave no identifiable a t room temperature, yielding 3.5 g. (0.013 moles, 40%) of compounds. The successful synthesis of IV bright yellow crystals, m.p. 214-216'. After three refrom dioxane-benzene the product melted employed 5-methyl-5-(2-aminophenyl)-hydantoin crystallizations a t 216-218'. (VII) as an intermediate, with either o-chloroaceto
