1360
\.I'ILLIAM
s. JOHNSON,
HOWARD c. E
JOHNSON AND JACK
W. PETERSEN
Vol. 67
free glassware; yield 0.86 g. of colorless carbinol, m. p. 320-340' for six to seven hours, the mixture was tritu126-128O. The aforementioned. salt cake was treated rated with ethanol and filtered. On concentration and with ice and ammonium chloride and worked up as de- dilution :he filtrate yielded 0.62 g. of yellow needles, m. p. scribed above. The crystallized carbinol thus obtained 107-115 . This product was purified by conversion to amounted to 3.81g. of colorless microscopic crystals, m. p. the picrate and cleavage of the latter in benzene by pass129-131 '~ The total yield was 4.67g. or 86%. A sample age through a tower of activated alumina. In this way purified for analysis by two recrystallizations from the same 0.42 g. (44% yield) of colorless plates of l-methylpheineliurii was obtaincd as colorless plates, m. p. 132-133 '. nanthrene wasobtained. The rn.p. 116.5-118° (reported,I8 .4nai. Calcd. for C,sHlsO: C, 81.91; H. 8.02. Found: 118") was not depressed when the sample was mixed with an authentic specimen of the hydrocarbon prepared by (3, 84.97; H, 8.25. Dr. F. C. Meyer from l-keto-1,2,3,4-tetrahydrophe1,4-Dimethylphenanthrhrene (VIII).-A mixture of 4.50 g. nanthrene. of the carbinol VI and 0.46 g. of 30y0 palladium-charcoal catalyst'' was heated a t 310-320" for one hour by which Summary time 96% of thc calculated volume of hydrogen was Potassium t-butoxide has been found to be an evolveci. The residue was dissolved in ether, filtered and evaporated. After trituration with a few cc. of cold excellent agent for promoting the Stobbe conmethanol the residue was obtained as colorless needles, densation of a ketone with diethyl succinate. rn. p. 49-50.5";yield 3.14g. From the triturate was obProcedures are given for the introduction of a tained an additional 0.59 g. of the hydrocarbon, m. p. 17.&40.5", making the total yield 91%. After recrystal- propionic acid residue a t the site of the carbonyl lization from methanol a sample melted a t 50-51" (re- group of an aryl ketone. The steps involve (1) a porter1,L' 49.5-50°). A picrate was prepared according to Stobbe condensation with potassium t-butoxide, the reported procedure,ll and the product had the m. p. ( 2 ) acid-catalyzed decarbethoxylation of the 142.5-143.5' (reported," 143.5"). 1-Methylphenanthrene (VII).-According to the proce- resulting half-ester and (3) reduction. dure of Fieser and Joshell* for the dehydrogenation of An application of the above process to the syn1-keto-2-methyl-l,2,3,4-tetrahydrotriphenylene, a mixture thesis of 2'4-dimethylphenanthrene from 2-acetylof 1.04 g. of 4-keto-l-methyl-1,2,3,4-tetrahydrophenanthrene (V) and 0.1 g. of 30% palladium-charcoal1' was naphthalene is described. sealed in a tube filled with nitrogen. After heating a t (IS) R. D. Haworth, i b i d . , 1125 (1932). s l i ) iinstead and Thomas, J . Chem. S o i . , 1127 (1940)
MADISOS,WISCONSIN
RECEIVED MAY24, 1945
[ CONTRIBUTIOX FROM THE LABORATORY OF ORGANIC CHEMISTRY OF THE UNIVERSITY OF WISCONSIN]
The Stobbe Condensation with Tetralone-1. A Synthesis of 3 '-Keto-3,4-dihydro1,2-~yclopentenonaphthalene BY WILLIAMS. JOHNSON, HJWARD C. E. JOHN SON^ In this communication is described the first phase of a study of the use of the Stobbe condensation3 to build up the cyclopentanone fused ring structure which is characteristic of ring D of many of the sex hormones. By this method we have succeeded in synthesizing 3'-keto-3,4-dihydro-l,2-~pclopentenonaphthalene, VI, from tetralone-1, I, in 52-5470 over-all yield (Scheme A) by a process which can be carried out in a few hours. The method promises to be applicable to the synthesis of molecules more closely resembling the steroids.* The various reactions which were studied are outlined in the accompanying flow sheet. The condensation of tetralone-i (I) with diethyl succinate proceeded well in the presence of sodium rthoxide, but the reaction was much improved by the use of potassium t-butoxide as the condensing agent.6 The crystalline half-ester I1 thus was obtained in 89-94y0 yields. Treatment of I1 with (1) This work was assisted, in part, by a grant from the Wisconsin Alumni Research I'oundation. ( 2 ) Present address. Chemical Industries. 522 Fifth Avenue, L'ew York, N . Y . ( ' 3 ) C.: Jiihnson. (;uldiiian rrid Ychneider, 'l'eis J O U R K I L . 67, 1357 (18L3). ( 4 j Johnson and Petersen. r b i d . , 67, 1366 (19451. ( 5 ) See ref. 9. f o o t n o t e
*
AND JACK
W. PETERSEN
a mixture of acetic anhydride and acetic acid containing a catalytic amount of zinc chloride6 resulted in ring closure (Scheme,A) not into the aromatic nucleus, but into the unsaturated alicyclic ring to produce a keto ester, probably 111 (position of double bond uncertain). Like a 8keto ester (of which formula I11 is a vinylog) the cyclized product was decarbethoxylated readily by the action of a mixture of hydrochloric and acetic acids to give the crystalline 3'-keto-3,4dihydro-l,2-cyclopentenonaphthalene, VI. For the over-all synthesis it was unnecessary to isolate the keto ester 111; the decarbethoxylation step (111 -+ VI) could be effected simply by the addition of dilute hydrochloric acid to the cyclization mixture followed by a short period of heating. In this way the ketone VI was obtained as the semicarbazone in 58% yield from the half-ester 11. Evidence for the structure of the ketone VI was afforded by oxidation with permanganate to phthalic acid. Had the ring closed into the benzene nucleus, the expected oxidation product would have been benzene-1,2,3-tricarboxylicacid. The nuclear structure of VI was proved conclusively by sulfur dehydrogenation to the known (6) Cf. Fieser and He rshberg, THIS JOURNAL, SD, 1028 (1937)
THE STOBBE CONDENSATION WITH
Aug., 1945
1361
TETRALONE-1
FLOW SHEET 0
i 4,5-benzhydrindone-1,7 VIL, and comparisons of the latter with alkali. The proportion of lactone the ketone and oxime were made with authentic to acid was found to vary considerably with the specimens kindly supplied by Dr. Fieser. The rea&ion conditions. The results of a study of dehydrogenation of VI incidentally constitutes a this phenomenon will appear in a future comgood method of preparing VII. The position of munication. In the present report a procedure the double bond in ketone VI has not been proved, is given for obtaining simultaneously the lactone but is placed between the alicyclic rings by I V in 38% and the acid V in 53% yield. The position of the double bond in the unsatuanalogy to the structure of the corresponding rated acid V is uncertain, but the remaining struccompound in the phenanthrene series.' Alternate routes to the cyclic ketone involved ture was confirmed by dehydrogenation (as the decarbethoxylation of the half-ester I1 before ester) to the known 8-1-naphthylpropionic acid, cyclization. The cleavage was accomplished VIII.' Catalytic hydrogenation of V, moreover, easily by the action of a mixture of hydrochloric afforded the known j3-( 1,2,3,4-tetrahydro-l-naphand acetic acids. The evolution of carbon diox- thy1)-propionic acid, IX.8 Cyclization (Scheme C) of the unsaturated acid ide was complete after a short period of heating, and the product consisted of a simple mixture of V proceeded readily by the zinc chloride-acetic the lactone (IV) of j3-( l-hydroxy-l,2,3,4-tetra-anhydride method to give the ketone VI in 76% hydro-1-naphthyl)-propionic acid and the un- yield. Under the same conditions the lactone IV saturated acid V (position of double bond uncer- also was cyclized (Scheme B) to give VI, but in tain) which was easily separated by extraction of somewhat lower (62%) yield. 0
0
n "
IX
(7) Fieser and Gates, THISJOURNAL, 69, 2335 (1040).
X
0
XI
In a search for other methods of cyclization, the action of hydrogen fluoride on the acid V was investigated. Under very mild conditions (one minute in the cold) V was converted practically quantitatively into the lactone IV. When the reaction mixture was allowed to stand several (8) v, Braun and Reutter, Bcr.. 69, 1922 (1925).
1362
LVILLIAM S. JOHNSON, HOWARD C . E.
hours a t room teniperature, however, cyclizatioii was realized. I n sharp contrast t o the behavior ivith zinc chloride, very little of the ketohe I,-I&is formed. ’The ring closed instead ii&dy iiito tht. benzene nucleus giving a mixture oi ketonic products from which was isolated by chroiiiatographic adsorption 1 ,?J, 10-tetra1 thanone-7 (X),!’and :i ketone oi positioii, C13H12C), which absorbed iior one double bond) amount of hydrogen in tl1i. presence of pallaciiurn-charcoal catalyst to give X. The unsaturated ketone, thereforti, is assigned the structure XI. Although the position of the double bond is uncertain it is niost probably not 111 the ketonic ring, since such 3 structure woulrl I)e expected to isonierizt. to a phenol. The ketone X has been prepared previously by the aluminurn chloride cyclization of the chloride of ,$-( 1,2,:4,4tetrahydro-1-naphthyl)-propionic acid, 1X jre.b The properties of the ported yield :35-45~,~~~) substance obtained in the present work were in agreement with those reported. For direct coiiiparison we prepared the ketone X by cyclization with h \ - d r o p n flurritlc.. ‘f‘hca vieltl W;IS
M‘. PETERSEN
JOHNSON AND JACK
Vol. 67
’T d XIXI
CHXCO CHCO”O \
C HC0.H
8 I
\
/
xv
(itaconic acid structure), because of the following considerations. S o tetralone- 1 could be detected on mild oxidation of either the half-ester I1 or the dibasic acid XIIa. From a study of a large number of condensations Stobbe evolved the generalizatictn that ketones with a methylene group flanking the carbonyl group give rise mainly to pyrotartaric acids.” Thus the product of the e forniatiori of X on cyclization of L7 with Stobbe condensation with propiophenone-which hydrogen fluoride evidently involved dispropor- may be considered an open model of tetralone-1-tionation. The more highly unsaturated (de- was nine-tenths pyrotartaric acid derivative. Like hydrogenated) material which must have‘ been other pyrotartaric acid derivatives13 the dibasic iorrned concomitantly with X (or with t.he un- acid XIIa was dehydrated to the anhydride XI11 cyclized precursor of X) has not beeii isolated, only upon heating with acetyl chloride. Itaconic but iiiay have been represented, a t least in part, acids, in contrast, generally form the anhydrides by the more strongly adsorbed yellow fraction oi :it room temperature with this reagent.13r14 Dehydrogenation of the full ester XIIb followed the chromatogram which, however, was not obtained crystalline. I t is not possible t o decide by saponification afforded 1-naphthylsuccinic whether the disproportioiiation occurred before acid, XIV in 89% yield. The over-all process or after cyclization. The acid V is known to be constitutes a good synthesis of XIV. This subthermally susceptible to disproportionation!” but, stance has been described previously by Wislicenusl5 who reported that on fusion it lost carbon 011 the other hand, certain perinaphthanone derivatives are kiwwn to have excrptionally labile dioxide. In the present work it was found that water, not carbon dioxide, was eliminated upon hydrogens .: fusion to fortn 1-naphthylsuccinic anhydride, XV. Haberland and Heinrich” have described the synthesis of a ketone which may be the 6-methoxy Experimental16 derivative of VI. By a Reformatsky type of re@-Carbethoxy-+( 3,4-dihydro-l-naphthyl)-propionic Acid action between @-bromopropionic ester atid ( j - (11). (a1 B y fhe Sudil4nz Ethuside .Vethod.-To a chilled tnethoxytetralonc- 1 they obtained d- (i1,klihy- Yther suspension of 0.80 mole of alcohol-free sodiuni clro-ti-rnethoxy-I -naphthyli-propioIlic acid in 23- cthoxide (prepared from 18.4 g. of sodium shot arid X . 8 g . of ahsolute alcohol in 800 cc. of dry ether) was i
