June, 1951
2641
A NEWTYPEOF CAMPS REACTION
tered and evaporated under reduced pressure. The residue, the residue treated with 1 ml. of dry benzene, which was presumably the diazoketone, was a pale yellow viscous liquid. then removed under reduced pressure. The residual acid A suspension of 50 mg. of silver oxide in 5 ml. of anhydrous chloride was added to ethereal diazomethane and the diazomethanol was refluxed on a steam-bath until a silver mirror ketone was rearranged exactly in the manner described for was formed (15 minutes). Then a solution of the diazo- its isomer in the preceding section. A solution of the product, a viscous yellow liquid, in 6 ml. ketone in a few ml. of methanol and an additional 50 mg. of silver oxide were added and the whole was refluxed for eight of benzene and 40 ml. of petroleum ether (60-75') was hours. Evaporation of the filtered solution yielded a vis- passed through a column of alumina (150 X 7 mm.) which had been wet with petroleum ether. The following fraccous yellow liquid which could not be made t o crystallize. A solution of the product in 10 ml. of benzene was passed tions were collected: (1) 40 ml. pee. 5ml. benzene (noth2 ml. benzene (noththrough a column (150 X 7 mm.) of aluminum oxide (Fisher ing on evaporation) ; (2) 8 ml. p.e. Scientific Co.) A yellow band appeared near the top of the ing); (3) 5 ml. p.e. 5 ml. benzene (nothin ); (4) 5 ml. 5 ml. benzene (trace of colorless liquid? ; ( 5 ) 10 ml. column. Six 10-ml. portions of benzene (eluates collected p.e. in separate flasks) served t o wash through 100 mg. of color- benzene (45 mg. colorless liquid); (6) 10 ml. benzene (30 1 ml. methanol less liquid. The yellow material on the column was finally mg. colorless liquid) ; (7) 10 ml. benzene (30 mg. viscous yellow liquid) ; (8) 10 ml. benzene (viscous eluted by benzene-methanol and methanol. The colorless liquid (100 mg.), which did not crystallize yellow liquid). Small amounts of methanol were added to each fraction after evaporation and the solutions allowed to when seeded with the alpha (m.p. 126') or beta (m.p. 114') forms of the dimethyl ester of 7-methoxy-2-methyl-2-car- evaporate slowly but no crystals appeared except in (7). The colorless liquids in fractions 4 , 5 and 6 were combined boxy-1,2,3,4-tetrahydrophenanthrene-l-aceticacid (XI), was hydrolyzed by refluxing with a solution of 0.28 ml. of and hydrolyzed by boiling with a solution of 0.22 ml. of N N sodium hydroxide (sufficient for one ester group) in 2.5 sodium hydroxide in 2 ml. of methanol for three hours. ml. of methanol for three hours. The methanol was re- The acid ester was isolated as described in the preceding moved by evaporation in a current of air, and water and a preparation; yield 45 mg. of colorless solid, m.p. 14P147O. little alkali were added to dissolve the sodium salt of the From ether-petroleum ether it crystallized in needles ; acid ester. A small quantity of insoluble material was ex- m.p. 146-148' alone and when mixed with the product tracted into ether, the clear aqueous solution was acidified (m.p. 148-148') obtained from the isomeric acid ester. Fractions 7 and 8 were combined and dissolved in 10 ml. with hydrochloric acid and the precipitated acid ester was extracted with ether. Evaporation of the ether left a of benzene and passed through a 25 X 7 mm. column of colorless liquid which crystallized readily when scratched alumina and washed with two 1 0 4 . portions of benzene, under ether-petroleum ether. The colorless solid was col- one of 1: 1benzene-chloroform and finally chloroform. The lected on a filter; weight 50 mg., m.p. 143-145'. The first 10-ml. fraction contained colorless liquid which crysacid ester crystallized from ether-petroleum ether in color- tallized readily on scratching under methanol; the second less needles, m.p. 147-148". The neutral ester, presum- and thud fractions contained nothing and the last ones contained viscous yellow gum. The crystals from the ably the dimethyl ester of cis-1-carbon-2-methyl-2-carboxymethyl 7 - methoxy 1,2,3,4 tetrahydrophenanthrene fist fraction were collected on a filter; yield 10 mg., m.p. (X), prepared by means of diazomethane crystallized from 124-126'. From methanol the product crystallized in clusters of thick colorless plates; m.p. 126-127" alone and petroleum ether (60-75") in colorless needles, m.p. 7475'. Anal. Calcd. for CZIHUO~: C, 70.8; H , 6.7. Found: when mixed with authentic alpha form (m.p. 126-127', precursor of isoequilenin) of the dimethyl ester of cis-7C, 70.7; H, 6.7. methoxy -2 -methyl -2 -mrboxy 1,2,3,4 tetrahydrophenan(b) On cis-1 -Carboxy-Z-carbomethoxy-2-methyl-7- threne-1-acetic acid (XI) ; the melt solidified readily on methoxy-l,2,3,4-tetrahydrophenanthrene.-When 180 mg. cooling and on reheating melted at 126-127'. of the acid ester (IX, m.p. 156-157') was added to a soluUltraviolet Absorption Spectra.-Ethanol was used as the tion of 1.2 ml. of oxalyl chloride in 1.2 ml. of benzene a solvent for all of the compounds in the figures the excrust of solid formed on the bottom and adhered to the glass. ception of the anhydrides Ia and I b for whichwith chloroform By tapping and swirling, the solid was dislodged and finally was employed. (15 minutes) went into solution. After two hours the yelRECEIVED DECEMBER 4,1950 low solution was evaporated under reduced pressure, and ANN ARBOR,MICH.
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[CONTRIBUTION FROM
THE
CONVERSE MEMORIAL LABORATORY OF HARVARD UNIVERSITY AND INSTITUTE]
-
THE
NATIONAL HEART
Ring Effects in Autoxidation. A New Type of Camps Reaction1p2 BY
BERNHARD WITKOP,'
JAMES
B.
PATRICKS8*AND
MYRONROSENBLUM
2,3-Cyclopentenoindole (I), by catalytic oxidation as well as autoxidation, is readily converted t o l-aza-7,8-benzcyclooctanedi-2,6-one (VII), opened by base (and acid) to yield 6-o-aminobenzoylbutyric acid (IX). The homologous lactam (VIII) with base undergoes a new type of Camps reaction to yield 2,3-cyclopenteno-4-quinolone(X), while the homologous 10-membered lactam undergoes intramolecular angular condensation to tetrahydrophenanthridone (XI). 2,3-Cyclo6ctenoindole (IV) is easily converted to the 2-keto derivative VI by autoxidation, VI was synthesized by applying the JappKlingemann reaction to 2-hydroxymethylenecyclooctanone. Attention is directed to the diagnostic value of the infrared and ultraviolet absorption spectra of a- arid y-quinolones, permitting an easy distinction between the two types of compounds.
It has been shown that catalytic oxygeriation,6,6 bazole (11) into the hydroperoxide V (n = 6) which as well as aut~xidation,~ converts tetrahydrocar- easily rearranges to the lactam (VIII). We have now extended these reactions to homologous (1) On the Mechanism of Oxidation. 11. First paper in this series. THIS JOURNAL, 78, 2196 (1951). tricyclic indole derivatives in which the size of the (2) Presented in part before the Summer Symposium on Natural isocyclic ring C varied from 5 to 8 members. Products, University of New Brunswick, Fredericton, N. B., August The results are summarized in the chart.* 22-26, 1950. Whilst tetrahydrocarbazole (11) is stable in var(3) National Heart Institute, Washington 14, D. C. (4) Research Corporation Fellow 1960. ious solvents (ethyl acetate, chloroform, alcohol, '79, 633, 1428 (5) B. Witkop and J. B. Patrick, THISJOURNAL, etc.), 2,3-cyclopentenoindole (I)9 in solution (e.g., (1950). (6) B. Witkop and J. B. Patrick, $bid., 78, 2188 (1951). (7) R . J. S . Beer, L. McGrath and A. Robertson, J . Chem. SOC.,
2118 (1950).
(8) Cf.J. B . Patrick, M. Rosenblum and B. Witkop, Expericntia, 6, 461 (1950). (9) W. H. Perkin and S . G. P. Plant, J . Chem. SOL, 198, 3244 (1923).
2642
HERNIMKLI h\’TTKOP, JAMES
B.
l-’ATRICK AND
MYRONKOSENBtUhl
\.ol. 73
HO@ in = 10
J ’ >
;o:
I
N
SI11
SXI, m p 80-81”
chloroform) is very unstable and changes rapidly (10 to 40 hours) into the lactam (VII). The intermediate hydroperoxide was not isolated. Catalytic oxygenation of I, after a short induction period (Fig l ) , directly led to the same lactam (VII). Figure 1 represents the rates of oxygen uptake for the four homologs I-IV. __
3 2 r -
-
___-
~
-1
XII, m.p. 133”
0
XI, m.p. 268”
(Fig. 3; ref. 6, Fig. 1A). Figure 4X shows one of the possible conformations of VI11 in a Stuart model. It is impossible to construct a model of VI11 which avoids the thermodynamically unfavorable “opposed” conformations.11 Since an ionic excited state of VI11 is necessarily planar, the rigidity of the lactam accounts for the hypsochromic effect observed. This rigidity diminishes with increasing size of the lactam ring as the iiiodel for an 11-membered lactam (Fig. 4 R )
