18-Norandrosta-8,11,13-trienes. Part IV. 7-Hydroxy-derivatives

摘要

336 J.C.S. Perkin I18-Norandrosta-8,l I ,I 3-trienes. Part 1V.l' 7-Hydroxy-derivativesBy Colin L. Hewett, Samuel G. Gibson, lain M. Gilbert, James Redpath,' David S. Savage, ThomasSleigh, and Robert Taylor, Scientific Development Group Organon, Organon Laboratories Ltd., Newhouse,Lanarkshire MLI 5SH, ScotlandDirect dehydrogenation of 18-norandrost-13-enes (1 a and b) with selenium dioxide gave the corresponding7~-hydroxy-18-norandrosta-8,11 ,I 3-trienes (2a and b) in one step. The corresponding 7a-acetates (2c and d)were obtained together with the epimeric 7P-acetates (9a and b) on treatment of the 18-norandrosta-7.13-dienes(8a and c) with mercury(i1) acetate. The mechanisms for both aromatisation processes are discussed.PREVIOUS papers described the formation of ring-c-aromatic steroids from 18-norandrost-13-enes, byusing bromination-dehydrobromination to introduce thetwo additional double bonds.In continuation of ourprogramme to evaluate the biological activities ofring-c-aromatic compounds the present paper describestwo useful routes to 18-norandrosta-8,11,13-trieneshydroxylated at position 7 : the reaction of 18-nor-androst-13-enes with selenium dioxide and the re-action of 18-norandrosta-7,13-dienes with mercury (11)acetate .The introduction of further double bonds into unsatur-ated steroids by using selenium dioxide is a well estab-lished technique,2 proceeding by allylic hydroxylation gfollowed by dehydration of the alcohol formed.2aygApplication of this reaction to the 18-norandrost-13-enes(la and b) gave, in one step, the 7a-hydroxy-18-nor-androsta-8,11,13-trienes (2a and b).The structureswere confirmed by the n.m.r. spectra of the acetates(2c and d), which show a quartet due to two aromaticprotons (6 7.02 and 7.27, JAB 8 Hz) and an equatorial7P-proton signal (6 5.9-6-0, Wi 6 Hz).The reaction is presumed to proceed as shown inScheme 1 by allylic hydroxylation of the 13,14-doublebond at either position 8 or position 12 to give the un-saturated alcohols (3) or (4). Since no products fromprocesses involving unsaturation or oxidation at position15 are isolated, it is assumed that no allylic attack occurs( 1 I a; R = H ( 2 I a; R ' = R ~ = Hb; R = O H b; R'=OH, RZ= Hd; R' = OAC, R2=AcC; R = OAc c; R' =H, R L A Cat that position.Under the conditions of the reactionboth alcohols (3) and (4) undergo dehydration with1 (a) Part 111, C. L. Hewett, S. G. Gibson, J. Redpath, andD. S. Savage, J.C.S. Perkin I , 1974, 1432; (b) Part 11, C. L.Hewett, I. M. Gilbert, J. Redpath, D. S. Savage, J. Strachan, T.Sleigh, and R. Taylor, ibid., p. 897.(a) N. Rabjohn, Org. Reactions, 1949, 5, 331; (b) J. C. Eckand E. W. Hollingsworth, .J. Amev. Chem. Soc., 1942, 64, 140;(c) A. L. Morrison and J. C. B. Simpson, J . Chem. SOC., 1932, 1710;(d) R. K. Callow and 0. Rosenheim, ibid., 1933, 387; ( e ) L.. J.Bellamy and C. DorCe, ibid., 1941, 176; (f) R. K. Callow, abzd..1936, 462; (g) L. F. Fieser and G. Ourisson, J . Amer. Chem. SOC.,1953, 75, 4404.allylic rearrangement, which appears to be the preferredmode of elimination,2 to give the dienes (5).Hydroxyl-ation of the dienes (5), again in the allylic positions,or I1SCHEME 1gives the 7,l l-diols (6), which lose the 1 l-hydroxy-groupalong with the 9a-proton, possibly also with allylicrearrangement within ring c, to give the 7a-hydroxy-18-norandrosta-8,11,13-trienes (2a and b) . * Some acid-catalysed dehydration also occurs, due to the presence ofthe selenous acid, and small amounts of 18-norandrosta-6,8,11,13-tetraenes (7a and b) can be detected in thecrude products.The introduction of a further double bond 2b,3 or of anallylic acetoxy-group into an olefinic compound byusing mercury(I1) acetate is a well known reaction,believed to occur by electrophilic attack of mercury(I1)3 (a) W.V. Ruyle, T. A. Jacob, J. M. Chemerda, E. M.Chamberlin, D. W. Rosenburg, G. E. Sita, R. L. Erickson, L. 11.Aliminosa, and M. Tishler, J. Amer. Chem. Soc., 1963, 75, 2604;(b) .A. Ziircher, €3. Heusser, 0. Jeger, and P. Geistlich, Helv.Chzm. Acta, 1964, 37, 1662; (c) A. Windaus and 0. Linsert,Annalela, 1928, 485, 148; (d) A. Windaus, ibid., 1931, 4861, 91;( e ) A. Windaus, U. Riemann, and G. Ziihlsdorff, ibid., 1942, 552,135; (f) D. H. R. Barton and W. J. Kosenfelder, J . Chem. Soc.,1951, 2381; ( g ) G. Saucy, P. Geistlich, R. Helbling, and H.Heusser, Helv. Chim. Ada, 1954, 37, 250.4 (a) W. Troibs, G. Lucius, H. Kogler, and H. Breslauer,Annalen, 1953, 581, 59; (b) W. Treibs and H. Bast, ibid., 1949,561, 165; (c) W.Treibs and I. Weissenfels, Chem. Ber., 1960, 98,13741975 337acetate on the double bond to give a symmetrical ion:followed by elimination of a proton to form an inter-mediate with the mercury atom at the least substitutedposition.6 This undergoes solvolytic demurcuration togive an allylic acetate, either by a concerted attack3for via an allylic carb~cation.~" With unstable allylicacetates the elements of acetic acid are lost to introducea second double bond. It seemed probable thereforethat treatment of an 18-norandrost-13-ene with mercury-(11) acetate would give either an allylic acetate or adiene, and that a subsequent similar step might reason-ably be expected to give an aromatic product. How-ever, the 18-norandrost-13-enes (la and c) wererecovered after treatment with mercury(I1) acetate, aresult probably due to steric hindrance associated withthe 13,14-double bond.Treatment of the 18-norandrosta-7,13-dienes l b (8aand c) with mercury@) acetate, however, resulted in amixture of the corresponding 7a- and 7P-acetoxy-18-norandrosta-8,11,13-trienes (2c and d) and (9a and( 7 ) a ; R = H ( 8 ) a; R = Hb; R =OHC ; R = OACb; R = OHC; R =OAc( 9 ) a ; R = Hb; R = OAcb), respectively. The reaction is believed to involveformation of the ion (10) by electrophilic attack acrossthe 7,8-double bond as shown in Scheme 2.A protonis eliminated to give an organomercurial intermediate(1 1), which undergoes demercuration via a delocalisedcarbocation (12) to the 7-acetate (13).A similarelectrophilic attack on this diene (13) by mercury@)acetate gives the aromatic 7a- and 7P-acetates. Ifthe reaction is carried out at reflux temperature orfor a prolonged period, the presence of the correspondingtetraenes (7a and c) in the reaction mixtures can bedemonstrated.The pure 7a-acetate (2d) isolated from the epimencmixture was identical with the product obtained viaselenium dioxide. The 7P-epimer (9b) could not be(a) I<. B. Wiberg and S. D. Nielsen, J. Urg. Chem., 1964, 29,3363; (b) 2. Rappoport, P. D. Sleezer, S. Winstein, and W. G.Young, Tetrahedron Letters, 1966, 3719; (c) 2. Rappoport, S.Winstein, and W. G. Young, J. Amev. Chem. Soc., 1972,@4, 2320;(d) 2. Rappoport, L. K. Dyau, S.Winstein, and W. G. Young,Tetrahedron Letters, 1970, 3483. * P. D. Sleezer, Ph.D. Thesis, U.C.L.A., 1963, cited in ref. Sb.obtained pure.the epimers (Bc) and (9a)I could be achieved.In the other series no separation ofH( 10 1 ( 1 1 1( 13 1 (12 1SCHEME 2 R=HorOAcThe 18-norandrosta-6,8,11,13-tetraenes (7a and b)could be obtained in good yield by treatment of thealcohols (2a and b), the acetates (2c and d), or the epi-meric mixtures with sulphuric acid. The assignmentof the additional double bond to position 6 is confirmedby the n.m.r. spectra of the compounds, which show boththe 6- and 7-proton signals as quartets (6 5.64 and 6.53,respectively) because of coupling with the adjacent5a-proton ( J 2-3 Hz). This confirms that the originalacetate group is at position 7 and discounts the possi-bility that the products from the mercury(I1) acetatearomatisation could be 15-acetates since these wouldbe deacetoxylated to give A16-compounds which wouldshow both 15- and 16-proton signals as doublets in then.m.r. spectra.Additional evidence on this point isprovided by the ketones (14a and b) produced on oxid-ation of the alcohols (2a and b). The i.r. absorption ofthe 7-carbonyl group occurs at 1667-1677 cm-l (typicalfor an a-tetralone 7, whereas the 15-ketone would beexpected7 to show i.r. absorption characteristic of anindanone at 1705-1715 cm-l.EXPERIMENTALM.p.s were determined with a Kofler hot-stage apparatus.1.r. spectra were determined with a Perkin-Elmer 457spectrometer.U.V. spectra were determined with a7 (a) L. J. Bellamy, The Infrared Spectra of ComplexMolecules,' Methuen, London, 2nd edn., pp. 137-138; (b) D. C.Gutsche, J. -4wzer. Chem. SOC., 1951, 73, 786J.C.S. Perkin IPerkin-Elmer 402 spectroineter and are for solutions inethanol. Optical rotations were measured for solutionsin chloroform at room temperature unless otherwisestated. G.1.c. was performed with a Pye-Argon chromato-graph. N.m.r. spectra (solvent CDC1,) were determinedat 60 Hz with a Varian A60 or a Perkin-Elmer R12 Bspectrometer, with tetramethylsilane as internal standard.Light petroleum refers to the fraction of b.p. 40-60".Unless otherwise stated, products were isolated bydiluting the reaction mixture with water, extracting withether, washing the extract with sodium hydrogen carbonatesolution and water until neutral, drying (IL'a,SO,), andremoving the solvent under vacuum.17,17-DimethyZ-18-no~-5a-androst- 13-ene (la) .-A sus-pension of 17a-methyl-5a-androstan- 17p-01 (25.0 g) in98-100~o formic acid (80 ml) was boiled under refluxfor 15 min, cooled, diluted with water, and filtered. Thesolid was washed neutral with water, dried in vacuo, andrecrystallised from acetone to give 17,17-dimethyZ-l8-nor-5a-androst-13-e~e (la) (20.6 g) as prisms, m.p.58-60',a, -39' (c lel), A, 214 nm (c 2700), 6 0.76 (3H, s, IO-Me)and 0.93 (6H, s, 17,17-hte2) (Found: C, 87.9; H, 11.6.C,,H,, requires C, 88.2; H, 11.8).17,17-DiunetJzyl-l8-nor-5a-androsta-7,13-diene (8a) .-Bro-mine (42 ml) in methylene chloride (40 ml) was addedslowly to a solution of 17,17-dimethyl-l8-nor-5a-androst-13-ene (la) (137 g) in ether (840 ml) and methylene chloride(I40 ml) at -70".The temperature of the solution wasthen allowed to rise to -15". Sodium iodide (160 g) inacetone (1.1 1) was added slowly, and the solution washeated to reflux temperature, boiled for 45 min, cooled,diluted with ether (1-5 l), washed in turn withaqueous sodium sulphite, water, and brine, and dried.The solvent was evaporated off and the residue was dis-solved in acetone (200 ml) ; the product was precipitatedby addition of aqueous sodium sulphite at 0". The solidwas filtered off, redissolved in acetone, and reprecipitatedwith aqueous sodium sulphite.The product was isolatedand dissolved in ether; the solution was filtered through acolumn of acid-washed alumina (1 kg), which was theneluted with ether. Evaporation of the eluate and crystal-lisatioii of the residue from ether-methanol a t 0 - 5 O gavethe 7,13-diene (8a) (1 18 a). Recrystallisation from thesame solvent furnished a sample of m.p. 46--50°, a,- 192" (c 2.2), Amxe 24'7 nni (E lS,SOO), S 0.93 (3H, s, 10-Me),0-99 (6H, s, 17,17-Me2), and 5.38 (lH, m, 7-H) (Found:C, 89.0; H, 11.3. C,,H,, requires C, 88.8; H, 11.2).17,17-DinzethyZ-l8-nor-5a-androst~-8,11,13-trien-7a-ol(2a).--,4 solution of 17,17-dimethyl- 18-nor-5a-androst- 13-ene(la) (20 g) in dioxan (100 ml) and water (20 ml) was heateduntil it was almost boiling, selenium dioxide (30 a) wasadded, and the mixture was boiled under reflux for 20 min,cooled, and filtered.The filtrate was diluted with waterand the product (22.0 g) was isolated and dissolved inlight petroleum (40 nil). The solution was filtered down acolumn (3 x 1 in) of alumina. EIution with light petrol-eum (150 ml) yielded a fraction (18.1 g) which was re-chromatographed in light petroleum on a column (10 x2.5 in) of alumina. Elution with light petroleum (1-2 1)and benzene (1.4 1) yielded impure fractions which werediscarded; further elution with benzene (1.0 1) and diethylether (1-2 1) yielded a fraction (9.3 g) which was crystal-lised from light petroleum to give 17,17-dimethyZ-l8-nor-5ct-* The more downfield signal is assigned to the 1 l-H by analogywith the l-oxo- and l-hydroxy-analognes.laandrosta-8,11, 13-trien-7u-oZ (2a) as prisms, m.p.118-121.5', aID +13O (c l-O), vmx, (KC1) 3400 (OH) and 818cm-l (aromatic), 1- 270 (E 1150) and 278 nm (1260)(Found: C, 84.3; H, 10.0. C,,H2,0 requires C, 84.45,H, 9.9).. Treatment of the corresponding 7,13-dienes (8) withselenium dioxide under the same conditions gave in-tractable mixtures.Tcc-Ace#oxy-17,1'7-dimethyl- 18-nor-6ol-and~osta-8,11,13-tri-ene (2c) .-Acetylation of 17,l 7-dimethyl- 18-nor-5a-andro-~ta-8,11,13-trien-7a-ol (2a) (1.22 g) in pyridine (5 ml) andacetic anhydride (5 ml) overnight at room temperaturegave the 7u-acetate (2c), which crystallised from acetoneas prisms (800 mg), m.p. 113-115.5", a, +43" (c 1-07),vms (CH,Cl,) 1725 and 1240 (3-OAc) and 824 cm-1 (aro-matic), 6 1.02 (3H, s, 10-Me), 1-19 and 1.26 (6H, 2s, 17,17-Me,), 2.04 (3H, s, 7a-OAc), 2.7 (2H, m, 15-H,), 5.9 (lH, m,7P-H), 7.02 (lH, d, J 8 Hz, 12-H), and 7-27 (lH, d, J 8 Hz,ll-H) (Found: C, 81-1; H, 9.4.C22H3002 requires C,8049; M, 9.3).Treatment of 17,l'I-DimethyZ- 18-nor-5u-androsta-7,13-d2-ene (8a) with Mercuvy(I1) Acetate.-A solution of the diem(8a) (100 g) in dioxan (250 ml) and acetic acid (750 ml) wasstirred with a suspension of mercury(I1) acetate (200 g)a t 70' for 40 h. The solution was filtered through Dicalite,cooled, and diluted with water (10 1). The product wasisolated by extraction and the residue (108 g), dissolvedin dry ether (1 l), was added carefully to a stirred suspensionof lithium aluminium hydride (36 h) in dry ether (1.2 1).The suspension was stirred at room temperature for 20min, diluted carefully with aqueous ether (3 l), and filteredthrough Dicalite.The solution was dried (MgSO,),concentrated, and chromatographed on a column of acid-washed alumina 8 (1.5 kg). Elution with cyclohexanegave starting material (12.0 g). Further elution withether gave a mixture of 7a- and 7p-epimers of 17,17-di-methy1-18-nor-5a-androsta-8,11,13-trien-7-o1 (68 g), 6 1-01(3H, s, IO-Me), 1.25 (6H, s, 17,17-Me2), 1.68 (lH, s, 7-OH),3.0 (ZH, m, 15-H), 4.77 (W, 5 Hz, 7P-H), 5.0 (Wa 7 Hz,7a-H), and 7.02 and 7.23 (2H, q, J 8 Hz, 11- and 12-H).17,17-Dimethyl-l8-nor-5a-androst- 13-ene (la), treatedwith mercury(I1) acetate in a similar manner, was un-changed.17,13-DimelhyZ-18-nor-5a-androsta-6,8,11,13-tetraene (7a).-(a) A solution of 17,17-dimethyl-I 8-nor-Sa-androsta-8,11,13-trien-7a-01 (2a) (1.0 g) (prepared by using seleniumdioxide) in dioxan (10 ml) was heated under reflux withsulphuric acid ( 1 0 ~ ; 0.05 ml) for 20 min, then cooled;the product was isolated by the normal procedure andcrystallised from ether-propan-2-01 to give the tetraene (7a)(337 mg), m.p.57-59-5, .ID -153" (c l-O), vmx. (KC1)3040 and 823 cm-1 (aromatic), Amx. 273 nm (c 9600) (Found :C, 90.1; H, 9.8.(b) A solution of a mixture of 7a- and 7P-epimers of17,1'7-dimethy1-18-nor-5a-androsta-8,11,13-trien-7-ol (10 g)(2a) and (9a) prepared by using mercury(r1) acetate washeated under reflux in dioxan (100 m1) with sulphuric acid(ION; 10 ml) for 15 min.The product was isolated andcrystallised twice from methanol-ether to give the tetraene(7a) (7.8 g), m.p. 55-57", 6 0.97 (3H, s. 10-Me), 1.26 (3H,s, 17-Me), 1.30 (3H, s, 17-Me), 6.64 (lH, q, J 10 and 2 Hz,6-H), 6.63 (IH, q, J 10 and 3 Hz, 7-H), 6-92 (lH, d, J 8Hz, 12-H), and 7.09 (LH, d, J 8 Hz, Ll-H) (Found: C ,8 I<. K. Farrar, J . C. Hamlet, H. B. Henbest, and E. R. H.Jones, J . Chem. SOC., 1952, 2867.C,,H,, requires C, 90.2; H, 9.8)1975 33990.3; H, 9.8), identical (u.v. and i.r. spectra and t.1.c.)with the sample prepared before.(14a).-Jones reagent (60 ml) was added slowly at 20"to a solution of 17,17-dimethy1-18-nor-5a-androsta-8,11,13-trien-7~- and -7p-01 (68 g) in acetone (650 ml) andstirring was then continued for 10 min.The product wasisolated and crystallised from methanol-water to give the"-ketone (14a) (51 g). Recrystallisation from the samesolvent gave a sample of m.p. 66-67', a, +68' (c 1-22),vn= (KCl) 1670 (7-ketone) and 830 cm-I (aromatic), vmX.CCH2C1,) 1667 and 830 cm-l, A,,, 257 (c 10,500) and 314 nm(3500), 6 1.15 (3H, s, 10-Me), 1.22 (6H, s, 17,17-Me2), 2.41(2H, m, 6-H2), 3.29 (ZH, m, 15-H,), and 7-2 (2H, t, J 8 Hz,11- and 12-H) (Found: C, 85.1; H, 9-3. C,oH,,O requiresC , 85.1; H, 9.3).3p, 7a-Diacetoxy-17,17-dimethy1-18-nor-5a-androsta-8,11,-13-triene (2d) .-(a) A solution of 3P-hydroxy- 17,17-di-methyl- 18-nor-5a-androst- 13-ene ( 1 b) lb ( 18 g) in dioxan(90 ml) and water (18 ml) was heated until i t was almostboiling, then selenium dioxide (27 g) was added.Themixture was boiled under reflux for 5 min, filtered to removeselenium, and cooled; the product (19.5 g) was thenisolated and dissolved in ether. The solution was filteredthrough a column (5 x 14 in) of alumina. Elution withether followed by ethyl acetate gave a reddish brown gum(14.7 g) which was acetylated with pyridine (22-5 ml)and acetic anhydride (22.5 ml) on a water-bath for 2 h.The product was extracted into ether and the extract waswashed with ammonium hydrogen sulphate solution andwater, dried (Na,S04), and evaporated to dryness. Trit-uration of the residue (16.1 g) with ether yielded the3p, 7a-diacetoxy-triene (2d) (4.5 g) .Two recrystallisationsfrom ether furnished a sample of m.p. 208-5", a, +14O(c 0-8), vlllRX (KCl) 1723 and 1245 (3-OAc) and 832 cm-1(aromatic), A,, 223 (E 10,300), 272 (1780), and 280 nm(1780) (Found: C, 75.0; H, 8.3. C,,H,,O, requires C,75.0; H, 8.4).(b) Mercury(r1) acetate (160 g ) was added to a stirred,boiling solution of 3~-acetoxy-17,17-dimethy1-18-nor-5a-androsta-7,13-diene (8c) lb (80 g) in glacial acetic acid(800 ml) and heating under reflus was continued for 10 min.The solution was cooled and filtered through Dicalite, andthe product was isolated and crystallised from ether-hexane giving the 3P,7a-diacetoxy-triene (2d) (27 g). Re-crystallisation from ether gave a sample of m.p. 202-206",a, +6.5 (c 0.89), vmx. (KC1) 3070, 3030, and 1725 and1240 cm-l (OAc), vmax.(CH,Cl,) 1730 and 1225 (OAc),and 830 cm-l (aromatic), 6 1.10 (3H, s, 10-Me), 1.23 (3H, s,17-Me), 1.26 (3H, s, 17-Me), 2-08 (3H, s, OAc), 2-09 (3H,s, OAc), 2-83 (2H, m, 15-H,), 4.80 (lH, m, 3a-H), 5.99(lH, m, W4 6 Hz, 7P-H), 7.02 (lH, d, J 8 Hz, 12-H), and7.27 (IH, d, J 9 Hz, ll-H) (Found: C, 75.4; H, 8-7),identical (i.r. spectrum and t.1.c.) with the sample pre-viously prepared. Recrystallisation (ether-hexane) ofthe material from the mother liquors gave a second crop(21 g ) containing a mixture of the 3P,7a-diacetate (2d)and the 3/3,7@-diacetate (9b). The mother liquors slowlysolidified; trituration with methanol gave a solid whichcrystallised from ether-petroleum to yield 3P-acetoxy- 17,17-dimethyl- 18-nor-5a-androsta-6,8,11,13-tetraene (7c) (3.4 g),m.p.144-145', a, -114" (c 14), vmx. (KCl) 1725 and1230 cm-l (acetate), 6 1.0 (3H, s, 10-Me), 1.21 (3H, s, 17-Me),1.24 (3H, s, 17-Me), 2.03 (3H, s, OAc), 2-83 (3H, m, 5a-Hand 15-H,), 4.80 (lH, m, 3a-H), 5-64 (lH, q, 9.5 and 2 Hz,17,17-Dimethy,?- 18-nor-5a-androsta-8,11,13-trien-7-one6-H), 6.55 (IH, q, J 9.3 and 2 Hz, 7-H), and 7.0 (ZH, t,J 8 Hz, 11- and 12-H) (Found: C, 81.5; H, 8.9. CZ2H,,O,requires C, 814; H, 8.7).dime (14b) .-(a) A mixture of 3p, 7a- and 3p, 7P-diacetoxy-17,17-dimethyl-18-nor-5a-androsta-8,11,13-triene (Zd) and(9b)l (2 g) prepared by using mercury(I1) acetate, in ether(50 ml), was added slowly to a suspension of lithiumaluminium hydride (1 g) in ether (30 ml), and stirringwas continued a t room temperature for 4 h.Aqueousethyl acetate was added carefully and the solution wasfiltered through Dicalite and dried (Na,SO,) . The solventwas evaporated off to give 17,17-dimethyl- 18-nor-5a-androsta-8,11,13-triene-3p,7-diol (1.7 g) as an epimericmixture which could not be crystallised. The material(1.4 g) was dissolved in acetone (2.5 ml) (redistilled overpotassium permanganate), Jones reagent 9 (2 mi) wasadded slowly a t room temperature, and stirring wascontinued for 10 min. Isolation of the product andcrystallisation from ether-light petroleum gave the 3,7-dione (14b) (1.01 g) as needles. Recrystallisation fromether-light petroleum gave a sample of m.p. 150-152",a}, +SO" (c O - S S ) , vmx.(KC1) 3060, 1713 (3-ketone), 1677(7-ketone), and 830 cm-1 (aromatic), v,,, (CH,Cl,) 1710,1670, and 830 cm-l, A,, 258 (E 11,200) and 314 nm (3600),6 1.26 (6H, s, 17,1i'-Me,), 1.42 (3H, s, 10-Me), 3.33 (ZH, m,15-H,), and 7.33 (2H, t , J 10 Hz, 11- and 12-H) (Found:C, 81-3; H, 8-1. C2OH24OZ requires C, 81-0; H, 8.2).(6) Hydrolysis of 3p, 7a-diacetoxy- 17,17-dimethyl-1 €?-nor-5a-androsta-8,11,13-triene (2d) (0.9 g) (prepared by usingselenium dioxide), in methanol (9 nil), with aqueous potas-sium hydroxide ( 1 0 ~ ; 1 ml) gave the diol (2b) as a non-crystalline residue (0-74 g). Kiliani's reagent 10 (6 mi)was added to a solution of the diol (0.7 g) in acetic acid(5.0 ml) and the solution was stirred a t room temperaturefor 45 min.The product (0.5 g) was isolated and crystal-lised from ether to give the 3,7-diketone (14b) as needles,m.p. 148-152', aID +58' (c 1-1), identical (i.r. spectrumand t.1.c.) with the sample prepared before.17,17-DimethyZ-18-nor-5a-androsta-6,8,11,13-tetraen-3~-ol(7b).--A solution of 3~,7a-diacetoxy-17,17-dimethyl-18-nor-5a-androsta-8,11,13-triene (2d) (10 g) in dioxan (600 ml)containing sulphuric acid ( 1 0 ~ ; 25 ml) was heated underreflux for 2 h, concentrated (50 ml), and cooled. Theproduct (7.5 g) was isolated, transferred as a solution inether onto a column of deactivated alumina 8 (200 g),and eluted with ethyl acetate. Concentration of theeluate and crystallisation from light petroleum gave thealcohol (7b) (5.1 g). Recrystallisation from light petrol-eum gave a sample of m.p. 99-l0lo, a}, -138" (G 0-42),vmax. (KC1) 3280 (OH) and 820 cm-l (aromatic), vmx.(CH,Cl,) 3600 and 825 cm-l, Amx. 273 nm ( E 11,400), 6 1.02(3H, s, 10-Me), 1.23 (3H, s, 17-Me), 1-27 (3H, s, 17-Me),2.87 (2H, m, 15-H,), 3.7 (lH, m, 3a-H), 5-65 (lH, q, J 9.3and 2 Hz, 6-H), 6-55 (lH, q, J 9.3 and 2 Hz, 7-H), and7.0 (2H, t, J 8 Hz, 11- and 12-H) (Found: C, 85.3; H,9.5.17,17-Dimethyl- 18-nor-5u-androsta-6,8,11,13-tetraen-3-one.-Jones reagent (6 ml) was added slowly a t room tem-perature to a stirred solution of 17,l'l-dimethyI- 18-nor-5a-androsta-6,8,11,13-tetraen-3~-01 (7b) (4 g) in redistilledacetone (40 ml) and stirring was then continued for 10 min.17,17-DimethyZ- 18-nor-5a-androsta-8,11,13-t~iene-3,7-CZoH2,O requires C, 85.1; H, 9.3).K. Bowden, I. M. Heilbron, E. R. H. Jones, and B. C. L.Weedon, J . Chem. SOC., 1946, 39.lo H. Kiliani, Ber., 1901, 84, 3664340 J.C.S. Perkin IIsolation of the product and crystallisation from ether- 17-Me), 2.9 (2H, m, 15-H2), 5.6 (lH, q, J 9 and 1 Hz, 6-H),hexane gave 17,17-d~rnetlzyl-l8-nor-5~-un~~osta-6,8,11,13- 6.62 (lH, q, J 9 and 2 Hz, 7-H), 6-97 (lH, d, J 8 Hz, lBH),tetraea-3-one (2.8 g). Recrystallisation from ether-hexane and 7.13 (lH, d, J 8 Hz, 11-H) (Found: C, 85.9; H, 8.7.furnished a sample of m.p. 155-157°, vmx. (KCl) 3030, 1720 C,,H2,0 requires C, 85.7; H, 8.6).(ketone), and 820 cm-l (aromatic), 274 nm ( E 9900),6 1.20 (3H, s, 10-Me), 1-23 (3H, s, 17-Me), 1-26 (3H, s, 411763 Received, 21st August, 1974