12
Vol. 67
NORMAN H. CROMWELL AND HERMAN HOEKSEMA
4-Methyltluorerol, VIII,-A mixture of 0.445 g. of VII, 2 g. t-8 zinc dust, 20 cc. of ethanol and 3 cc. of 28% ammonium hydroxide was refluxed for two and a half hours. The hot mixture was filtered and the filtrate poqed onto ice. The precipitate, which contained some unchanged ketone, was dried and recrystallized from benzene-petroleum ether. The first crop gave 0.210 g (47%) of colorless very fine needles, m. p. 160-162.5", which when recrystallized from benzene had a melting point of 164.0-164 6'. Anal. Calcd. for CllHI20: C, 8567; H, 6.16. Found: C, 84.78; H, 6.18. The mother liquor was chromatographed on a 1:l mixture of alumina and Super-Cel. The yellow band on elution gave 0.085 g. of unchanged ketone, m.p. 90.5-91.5°. Longer refluxing with intermittent addition of ammonium hydroxide did not increase the yield
[CONTRIBUTION FROM THE
a,@-Diamino Ketones.
I-MethyHuoreme, SII.-Reduction of 0.120 g. of VI11 with red phosphorus and iodine1n gave, after recrystalliza$on from methanol-water, 0.055 g. (50%) of 111, m. p. i 1.5-72.5'
SummaY
When 2,2'-dimethyIbiphenyl is repeatedly passed over a palladium-charcoal catalyst a t 450' it is converted to 4-methylfluorene. The synthesis of 4-methylfluorenone and its reduction to 4-methylfluorene are described. (16) Miller and Bacbman, THISJOURNAL, 67, 2448 (1935).
PITTSBURGH, PA.
AVERYLABORATORY OF CHEMIsrRY
RECEIVED OCTOBER 6, 1944
OF THE UNIVERSITY OF NEBRASKA]
III.' Reaction of 8-Amino-6-methoxyq~oline with a-Bromo-&amhoketones
BY NORMAN H. CROMWELL AND HERMAN HOEKSEMA~ a-Bromo-&uninoketones have been found to react readily with various heterocyclic secondary amines but less readily with open chain secondary amines' to give mixed diamino ketones. It was also shown that a primary amine might be used in these reactions.s Since certain of the diamino ketones which have resulted from these investigations have shown mild activity as avian abtimalarials it seemed importabt to attempt to introduce the plasmoquin base group into these molecules by treating various a-bromo-8-adnoketones with 8-amino6-rnethoq~quinoline,~with the hope that such R CHI R CH3 antimalarial activity might be enhanced. Although the entering amino group has always 8-Amino-6-methoxyquinoline,which is a relatively weak base, reacted quite readily with a been shown to take the &position in these moleseries of a-bromo-@-amhoketones to give good cules, it seemed necessary to prove by hydrolysis that one of these, namely (I), actually had the yields of the desired mixed diamino ketones. structure assigned. On acid hydrolysis (I) gave " 2 only the expected products, benzaldehyde, 8amino-6-methoxyquinoline and w-morpholino-acetophenone, isolated as'the oxime. Plasmoquin base was not strong enough to reC6H~-cH-CH-CO-R \ /- OCHs act with a,,3dhromoben2ylacetone or with abromobenzdaketone under the usual conditions. tJ. In an attempt to convert the keto to a hydroxy CBH,-CH-CH--CO--R group in (V), only non-resolvable oils resulted I 1 from catalytic hydrogenation using palladium on ,S, Br charcoal or platinum oxide in glacial acetic acid CsHs-CH-CHCO-R solutions. These diamino ketones -seem quite I I resistent to reduction by any of the usual methN-H Y I /*\ ods. Moreover, it was impossible to add the methyl Grignard reagent to (IV) to form the dlamino tertiary carbinol, although such additions have been accomplished with certain of the diamino ketones mentioned in previous paper^.^ (1) Previous paper in series: Cromwell, Caughlan and Gilbert, The carbonyl group seems to be quite hindered THISJOURNAL, 66, 401 (1944). (2) .Parke, Davis and Co. Research Fellow, 1943-1944. in many of these diamino ketones. (3) Cromwell, Harris and Cram, THISJOURNAL, 66, 134 (1944). Unsuccessful attempts were made to introduce (4) A supply of this base was generously furnished for this work
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