April 5, 1057
3-CARBETHOXY-As-OCTA1lYDRO-5,G-BEh‘ZINDAN-1-ONE
1757
[CONTRIBUTION FROM SCHOOL OF PHARMACY, LONDONUNIVERSITY,AND UNIVERSITY COLLEGEFOR GIRLS, EIN SHAMS UNIVERSITY]
Octahydrobenzindanes. Synthesis of 3-Carbethoxy-~~-octahydro-5,6-benzindan-1-one and 3-Carbethoxy-~~-octahydro-4,5-benzindan-l-one BY A. M. EL-ABBADY‘ RECEIVED OCTOBER 24, 1956 Stobbe condensation was carried on cis-2-decalone and trans-1-decalone with diethyl succinate. The resulting half-esters when ring closed gave 3-carbethoxy-A~-octahydro-5,6-benzindan-l-one and 3-carbethoxy-A~-octahydro-4,5-benzindan-lone, respectively. The structures of these compounds were proved.
Octahydrobenzindane compounds are of inter- sition and not in the 1,2-position. These findings est, as they could serve as intermediates in the suggest that structure I a of the half-ester is more preparation of analogs of steroid hormones. Their likely to be formed than structure I b where the structures represent rings B, C and D of the natu- double bond is in 1,2-position. Such supposition ral hormones. The procedure applied for their could explain the formation of the keto ester IVa synthesis had been used previously by Johnson, et and not IVb as i t is shown later on. Alkaline hya1.,2in the preparation of tetrahydroindanones. drolysis of the half-ester gave @-carboxy-@-(cis-2cis-2-Decalone was condensed with diethyl or A2-octahydronaphthy1)-propionicacid (11). When dimethyl succinate in the presence of potassium t- the half-ester was subjected t o catalytic hydrogenabutoxide to give the half-ester I (R = E t or Me), tion, i t absorbed one mole of hydrogen and gave as a colorless oil. The constitution of Ia (R = Et) after hydrolysis P-carbox -P-(cis-2-decahydroas R-carbethoxy-8-(cis-2-A2-octahydronaphthy1)-naphthyl)-propionic acid (IIIf Treatment of the propionic acid follows from the following observa- half-ester I a (R = Et) with a solution of zinc chlotions: The half-ester I failed to give any ketonic ride in acetic acid and acetic anhydride yielded a material on oxidation with alkaline permanganate. cyclic keto ester 3-carbethoxy-A8-octahydro-5,GIt also failed to reveal an absorption band in the benzindan-1-one (IVa), that was isolated from the region between 210-225 mp in ethanol, a character- reaction mixture as colorless oil when fractionated istic of a$-unsaturated ester^,^ thus excluding on an alumina column. Redistilled samples, howstructure IC. The fact that cis- and trans-2-deca- ever, seemed to be substantially of the stated struc101s when dehydrated give the corresponding cis- ture, as acid hydrolysis and decarboxylation gave a and tran~-A~-octalins,~ shows that the double bond homogeneous cr,P-unsaturated ketone V in 80% in the octalin is preferentially formed in the 2,3-p0- yield. The actual course of the reaction and partic0 ularly the structure of the keto ester IV is a matter of interest. Since the reaction is an intramolecuCOOH lar ring closure, the resulting keto ester would then appear to have the proposed structure IVa. c~@cooEt cI,”1HCH&OOH The ultraviolet absorption spectra of the unsaturated keto ester, the unsaturated ketone, their 2,4dinitrophenylhydrazones and their semicarbaIS’b zones confirm the presence of an a,@-unsaturated HOOC-CHI ketone grouping when compared with some general examples from the literature,6J and, more specificCOOR ally, with similar derivatives of tetrahydroindanones’ and octahydrobenzindanone.a To establish the structure of the keto ester IVa, the a,pIb unsaturated ketone V was dehydrogenated using 30y0 palladized charcoal, to give the known 5,Gbenzindane (Vl), as shown from its melting point Ia, El = Et (94’) and the melting point of its picrate (12011, R = H 121’) .s Its ultraviolet spectrum showed three IC maxima a t 226 mp (log E 4.89), 279 mp (log E R I 3.78) and 320 mp (log E 3.17), characteristic of naphthalene and 4,5-benzindane. lo trans-a-Decalone was similarly condensed in the presence of potassium t-butoxide with diethyl suc-
f
VI
IVa, R = COOEt V,R = H
(1) Chemistry Department, University of Michigan, Ann Arbor, Mi&. (2) W. S. Johnson, H. C. E . Johnson and J. W. Petersen, THIS JOURNAL, 67, 1360 (1945). ( R ) H. E. Ungnade and I. Ortega, ihid., 75, 1566 (1951). (4) W. Borsch and IC. I a r g e , A n l z . , 434, 219 (1923).
(5) (a) H. S French, THISJOURNAL, 74, 514 (1952); (b) E . A. Braude and E. R. H. Jones, J . C h o n SOC.,498 (1945). ( 6 ) L. K. Evans and A. E. Gillam, ibid., 565 (1943). (7) D.W.Mathieson, ibid.,177 (1951); J . C. Hamlet, 13. B. Henbest and E . R. H. Jones, ibid., 2652 (1951). (8) D. W.Mathieson, ibid.,3248 (1953). (9) S . C. Sen-Gupta, J. Indian Chem. Soc., 16, 89 (1939). He reported exactly the same melting points, (10) W. V. hlayneord and E &.I F. . Roe, Pvor Roy. Sor. ( T a n d o n ) , 8 1 6 2 , 290 (1035)
cinate t o yield P-carbethoxy-@-(1-Al-octahydronaphthyl)-propionic acid (VIT) .8 This on alkaline hydrolysis gave the corresponding diacid VIII, and when refluxed with a mixture of glacial acetic acid and hydrochloric acid yielded the paraconic acid
drogenated with rldanis platinum oxide (0.1 g . ) . Uptake s was almost complete in one hour. The product ~ 3 refluxed for 2 hr. with 107, sodium hydroxide solution, after which acidification yielded a colorless solid (0.8 g . ) crystnllizing from ethanol-light petroleum (b.p. 60-80"i; m.p. 174-176 O . A n d . Calcd. for C14Ha204:C, 66.1; H, 8.66. Found: COOH C, 65.7; H , 8.2. 3-Carbethoxy-A8-octahydro-5,6-benzindan-l-one(IVa) .The half-ester Ia (R = E t ) (40 g.) in freshly distilled acetic anhydride (700 ml.) was refluxed (under nitrogen) with 2% solution of fused zinc chloride in glacial acetic acid (350 ml.) for 6 hr. Excess anhydride and acid mere removed in COOK vacuo and the residue poured into water which was made 1.11, K = Et alkaline with sodium carbonate. A. dried ethereal extract 1.111, R = H on evaporation gave a dark brown resinified oil, which 011 distillation gave a pale yellow heavy oil, b.p. 160-162' 1.5160 (20 g., %Yo). I t gave a semicarba(0.2 mm.), 268 mp ( E 26,000). zone, m.p. 210-211 O, from ethanol, A,, 0 Anal. Calcd. for C17H2503x3: C, 63.95; H , 7.84; S , 13.17. Found: C, 63.57; H, 7.62; N, 13.77. Its 2,4-dinitrophenylhydrazone crystallized from ethanol iii red crystals, m.p. 133-134", Amax 388 mp ( E 33,000). Anal. Calcd. for C22H2606X4: C , 59.72; H , 5.88; N, 12.67. Found: C, 59.58; H , 5.65; N, 12.88. i I fi When the crude keto ester (2 g.) in dry thiophene-free \/ benzene (100 ml.) was passed over alumina (Savory and 1,R = COOEt S II Moore, Brockmann Standardized, 50 g., column size 13 X XI, R = H 2.4 cm.), a colorless oily fraction (0.6 g.) was obtained, b.p. (IX). The half-ester VI1 was then cyclized with 125-130" (0.05 mm.), A,, 239 mp ( E 10,000). Calcd. for CI6HZ2O3: C, 73.28; H , 8.39. Found: zinc chloride-acetic anhydride in acetic acid to give C,Anal. 73.08; H, 8.26. exclusively 3-carbethoxy-A8-octahydro-4,5-benzin- A8-0ctahydro-5,6-benzindan-l-one (V) .-A mixture of dan-1-one (X) as a colorless oil. Hydrolysis and the ethyl keto ester (5.2 9.) and concentrated hydrochloric decarboxylation of the keto ester X yielded the acid (80 ml.) was refluxed for one hour. After dilution with known A8-octahydro-4,5-benzindan-1-one (XI).g water, it was ether-extracted. The ether extract mas washed sodium carbonate solution, water and dried over anThis was hydrogenated a t a palladium catalyst and with hydrous sodium sulfate. Removal of the solvent gave cl gave the decahydro-4,5-benzindan-l-one (XII). g residue which was distilled a t 120' (0.8 mm.) as a colorless ~ A,, 238 rnp ( E 12,000), yield 3 g. (8070). oil, n 2 0 1.5415, Experimental' Anal. Calcd. for C13H180:C, 82.11; H, 9.47. Found: (3-Carbethoxy-p-(cis-2-A2-octahydronaphthy1)-propionic C, 81.81; H , 9.55. Acid (I).-To a solution of potassium t-butoxide (from poIts sernicarbazone crystallized froin ?t-but)-l ~ C I J ~ I ~ tassium, 5.6 g., and dry t-butyl alcohol, 100 ml.) were added m.p. 267.5-228.5' dec., AmSx 265 m p ( E 23,000). ~ cis-2-decalone (18 g.) (b.p. 105-106° (7 mm.), n 2 0 1.4927)12 Anal. Calcd. for C14H2:OSa: C, 68.02; H, 8.5; N, and diethyl succinate (30 g . ) . The mixture was refluxed 17.0. Found: C,67.97; H,8.69; S, 16.8. under nitrogen for 45 min. and then cooled in ice. Concentrated hydrochloric acid (20 ml.) in ice-water (20 ml.) ws: Its 2,4-dinitrophenylhydrazoiie crystallized from ethduolslowly added so that the temperature did not exceed 20 . xylene as dark red crystals, m.p. 216-218" dec., A,, 393 Excess of t-butyl alcohol was removed on the steam-bath and 265 mp ( E 27,600 and 111,250, resp.). in vacuo and the residue extracted with ether. The acid 4naZ. Calcd. for CISH22O4N4: C, 61.62; H, 5.94; X, fraction was isolated in the usual way with 10% aqueous 15.13. Found: C,61.59; H,5.80; N, 15.24. sodium carbonate. There resulted a viscous oil, b.p. 179Dehydrogenation of A~-Octahydro-5,6-benzindan-l-one ~ (yield 23 g., 68%). 180' (0.2 mm.), n Z 11.5013 (V) to 5,6-Benzidane (VI).-The unsaturated ketone (1 g . ) Anal. Calcd. for CL6HZ404: C, 68.6; H , 8.57. Found: was heated with (0.5 9.) of 30% palladized charcoal13for 4 hr. C , 68.98; H , 8.44. a t 280-300' in a stream of carbon dioxide. About 90%' of Repeating the above experiment using dimethyl succinate, the calculated amount of hydrogen was evolved. The conyielded the half-ester I a (R = Me) as a colorless oil, b.p. tents of the flask was then ether-extracted. The ethereal 172-173' (0.5 mrn.), f i z o ~1.5043 (6570). solution was filtered and the solvent removed. The brown Anal. Calcd. for C1&204: C, 67.67; H, 8.27. Found: crystalline residue (0.6 9.) was then distilled under vacuum giving a colorless solid crystallizable from methanol as C, 67.81; H, 8.05. p-Carboxy-p-(cis-2-A2-octahydronaphthyl)-propionic Acid plates, m.p. 94" (lit.9 m.p. 94'); Xma, 226, 279 and 320 I I I ~ (II).-The ethyl half-ester I a (2 g.) was refluxed in 10% (log E 4.89,3.78 and 3.17, resp.). Anal. Calcd. for Cl3Hi2: C, 92.8; H , 7.2. Found: sodium hydroxide solution (20 ml.) for 3 hr. Working up the reaction mixture as usual, gave an oil which solidified C, 92.32; H, 7.24. under light petroleum (b.p. 60-80"). This was crystalI t gave a picrate crystallizable from ethanol in long lized from benzene; m.p. 121-123' (1.6 g.). golden needles, m.p. 120-121' ( l i t . 9 n1.p. 120-121'). p-Carboxy-(3-(trans-l-al-octahydronaphthyl)-propionic Anal. Calcd. for ClaHnoO4: C, 66.66; H, 7.94; neut. equiv., 126. Found: C, 66.91; H, 7.99; neut. equiv., Acid (VIII) .-0-Carbethoxy-p - (trans- 1- Al-octahydronaphthy1)-propionic acid (VII)8 lras prepared by :he Stobbe con126. p-Carboxy-~-(cis-2-decahydronaphthyl)-propionicAcid densation of trans-1-decalone (m.p. 32-33 , ?z*"D 1.4856, (III).--The ethyl half-ester I a (1 g.), dissolved in a mixture and diethyl succinate. This half-ester (2 6.) was heated with 5% sodium hydroxide solution (20 ml.) on a steamo f et1i:rnol (5 nil.) and glacial acetic acid (15 mi.), was hy.. bath for 3 hr. The mixture was cooled, ether extracted, then carefully acidified with dilute hydrochloric acid. The (11) .\I1 melting points and boiling points are uncorrected; microcolorless solid obtained was crystallized from benzene-ligllt analyses are by G. S . Crouch, School of Pharmacy, a n d by A. Bernpetroleum (b.p. 60-80'); m.p. 173' (1.2 g.). hardt, Max-Plank-Institute, Miilhein (RuhrJ. Light absorptions were
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1
v
measured in ethanol f & the ketones, in 2% chloroform in ethanol for t h e s ~ , ~ , i ~ ~ atid ~ ~i nt chloroform ~ : ~ ~ ~ f,
