1976 1889Heterocyclic Steroids. Part lL1 Synthesis of (+8-Hydroxy-3-methoxy-11 -aza-I 8-norestra-I ,3,5(10),9(1 I )-tetraen-I 7-one and Related Com-poundsBy Dhanonjoy Nasipuri and Sanat K. Ghosh, Department of Chemistry, Indian Institute of Technology5-0~0-2-(1,2,3,4-tetrahydro-6-methoxy-2-naphthyl)cyclopent-l -enylacetic acid (11). readily available from 2-acetyl-l.2.3.4-tetrahydr0-6-methoxynaphthalene (I), was hydrogenated and then oxidised with chromic acid togive the dioxo-acid (IV). By a modified Curtius rearrangement this afforded (*)-9(1 l)-didehydro-8-hydroxy-l1-aza-1 8-norestrone 3-methyl ether (IX), the hydroxy-group being presumably introduced through autoxidation. Incontrast, similar treatment of the 13-methyl acids (V) and (VI) of the natural series gave the 3-methyl ethers of9(1l)-didehydro-l1 -aza-estrone (X) and -1 7P-estradiol (XI), which do not undergo oxidation in air.Kharagpur 721 302, IndiaRECENTLY, we have synthesised a 6,15-diazaequileninderivative by use of a modified Curtius rearrangement.2The reaction has now been employed for the totalsynthesis of an (amp;)-l l-aza-18-norestrone derivative(IX) (see ref.3 for a similar partial synthesis). The1 D. Nasipuri and S. K. Ghosh, J.C.S. Perkin I, 1974,2720 isregarded as Part I.J. G. Morgan, K. D. Berlin, N. N. Durham, and R. W.Chesnut, J . Ovg. Chem., 1971, 36, 1599.P. Yu. Badanova and K. K. Pivnitakii, Zhur. obshcheiKhim., 1971, 41, 242 (Chem. Abs., 1971, 75, 36,455q).method is capable of providing a direct route to ll-aza-estrogens 4 from easily accessible materials and affordsuseful intermediates for the synthesis of 9,ll-seco-steroids, a number of which have been synthesised latelyFor a review, see R.I. Blickenstaff, A. C. Ghosh, and C;. C.Wolf, ' Total Synthesis of Steroids,' Academic Press, New York,1974.J. H. Dygos and L. J. Chinn, J. Urg. Chem., 1973, 38, 4319;1975, 40, 685; L. J. Chinn, J. H. Dygos, S. E. Mares, R. L.Aspinall, and R. E. Ranney, J . Medicin. Chem., 1974, 17, 351 ;N. S. Crossley and R. Dowell, J. Chem. SOC. ( C ) , 1971, 24961890 J.C.S. Perkin Iin view of their modified biological activity. Someobservations on the autoxidation of imines resulting fromthe Curtius reaction are also recorded.0M e 0 a 'amp; bsol; OHMe0lIxltm,R2- Ace t y 1- 1,2,3,4- t et rah y dro-6-me t hox ynaph t halene(I) was prepared from $-anisaldehyde through thesequence of reactions shown in Scheme 1 in an overallyield of 40.The ketone was converted into 5-OXO-2-( 1,2,3,4-tetrahydro-6-methoxy-2-naph thyl) cyclopent-1-enylacetic acid (11) through its furfurylidene deriva-tive.6 The methyl ester was reduced catalytically andthe trans-isomer, obtained as the major product 7 washydrolysed to (j--)-3-methoxy-18-nor-17-oxo-9,1l-seco-estra-1,3,5(10)-trien-ll-oic acid (111). This was oxidisedwith chromic acid to the tetralone derivative (IV),obtained in moderate yield but easily separable from thereaction mixture. The position of the ketonic group wasconfirmed by spectral data (see Experimental section)6 R.Robinson, J . Chem. SOL, 1938, 1390; A. Koebner and R.Robinson, ibid., p . 1994; M . M. Coombs and T. S. Bhatt, J.C.S.Perkin I , 1973,1251 ; V. M. Kapoor and A. M . Mehta, ibid., p . 2420.L. J. Chinn, E. A. Brown, R. A. Mikulec, and R. B. Garland,J . Org. Chem.. 1962, 27, 1733; Y . Amiel. A. Loffler, and D. Gins-burg, J . Amer. Chem. SOC., 1954, 76, 3625. * See A. G. Cook, ' Enamines: Synthesis, Structure, andReactions,' Dekker, New York, 1969, p. 285, for references.L. A. Cohen and B. Witkop, J . Amer. Chem. Soc., 1955, 77,6595.and also by a model experiment in which y-(1,2,3,4-tetrahydro-6-methoxy-2-naphthyl) butyric acid was oxid-ised to the corresponding tetralone (VII). Both theketo-acids (IV) and (VII) were submitted to a modifiedCurtius reaction as described bef0re.l (-4) -8-Hydroxy-3-methoxy-1 l-aza-18-norestra-l,3,5,9( 11)-tetraen-17-one (IX) and 2,3,4,4a,5,6-hexahydro-4a-hydroxy-8-methoxybenzohquinoline (VIII) were obtained in 36I P - Me0 *C,Hi CH - C ICO,Et l2 --m p - M eO .C,HiC H i CHIC0,Et 1,iivI 1 1SCHEME 1 Reagents : i, H,..Pd-C; ii, NaOEt, ClCH,*CO,Et,hydrolysis and heat; 111, heating with Ac,O followed byhlC1,; iv, NH,*NH, and KOH or H,, Pd-C in AcOH-HC1;v, (EtO)MgC(CO,Et), on the derived acid chloride andhydrolysisand 50 yields, respectively.The insertion of thehydroxy-group is not surprising; many imines are sensi-tive to oxidation and are converted into hydroperoxideson exposure to air.8 The latter ordinarily decompose togive secondary products including p-hydroxy-iminesas (VIII) and (IX) in contact with solvent^.^ We were,however, unable to detect any hydroperoxide or otherby-products (such as cyclic 0x0-lactams) in the abovereactions.Further study is necessary to show whetherthe hydroxy-derivatives are primary oxidation pro-ducts10 or are merely formed by spontaneous decom-position of the hydroperoxides.The structure of the aza-steroid (IX) was supported byix., n.m.r., and mass spectra, and by elemental analysis.The mass spectrum showed prominent peaks at m/e 285(M+, 100yo), 268 (17, M - OH), 267 (14, M - H20),266 (12, M - H,O - H), 212 (41, M - OH - CH,:CH, - CO), 203 (SO), 175 (84), 174 (53), and 160 (24)(Scheme 2). The peak at m/e 203 corresponds to thefragment (XII), which confirms the position of thehydroxy-group.The peak at m/e 175 possibly arisesthrough elimination of OH, hydrogen migration, andextrusion of C,H,O* from C(12-17).The unsaturated 0x0-acid as (11) could, in principle,undergo reductive methylation l1 as reported in ananalogous case,12 and the product (usually a mixture oflo B. Witkop, J . Amer. Chem. SOC., 1980, 72,1428; B. Witkopl1 G. Stork, P. Rosen, N. Goldman, R. V. Coombs, and J.l2 A. J. Birch and G. S. R. Subba Rao, Aztst~al. J . Chem., 1970,and J. B. Patrick, ibid., 1951, 73, 713.Tsuji, J . Amer. Chem. SOC., 1965, 87, 275.23, 5471976 1891stereoisomers 13) could be used for the synthesis of 9,ll-seco-steroids 5 or be oxidised to the dioxo-acid (V).Thelatter, however, is available in natural configuration byoxidation of estrone methyl ether with chromic acid.l*The corresponding 17@-acetoxy-derivative (VI) haspreviously been converted into 1 l-aza-estrogens byRussian workers.3 Since the details of this work werenot available, we repeated the experiments with the oxo-acid (1') and its 17~-acetoxy-derivative (VI) under ourown conditions. In both cases, the ll-aza-steroid(X) and (XI) was obtained in ca. 50 yield, and each1,2,3,4-Tetrahydro- 6-methoxy-4-oxonaphthalerte-2-carb-oxylic A cid.-The oxo-acid was prepared essentially by aknown procedure,l6*1' as shown in Scheme 1: m.p. 158-159" (from ethyl acetate) (1it.,l6 m.p. 149-151') (Found:C, 65.8; H, 5.9. Calc.for Cl2Hl2O,: C, 65.5; H, 5.4),vmax. (Nujol) 1 700 and 1 660 cm-l.A amp;.-The foregoing oxo-acid was reduced by the Huang-Minlon procedure 16 as well as by hydrogenation over 10palladium-charcoal in acetic acid containing a few drops ofhydrochloric acid. The resulting acid had m.p. 156-157"(from ethyl acetate) (lit.,I6 m.p. 149-150") (Found: C,1,2,3,4- Tetrahydro- 6-methoxynaphthalene- 2-carboxylic1 - bsol;m/e 203 IXII 1+NH2___)Me0m/e 174 m/e 175 m/e 160SCHEME 2was characterised by n.m.r. and mass spectra. Nooxidation of the resulting imines was detected. Appa-rently, oxygen approaches the molecule from the P-sidesyn with respect to 13-H and trans with respect to 14-Hin (IX) and such attack is prevented in the 13p-methylaza-steroids (X) and (XI) by a syn-methyl interaction.This fixes the configuration of the hydroxy-group in thesynthetic compound as in structure (IX) (only oneenantiomer is shown).No hydroxylation occurs whenthe p-carbon atom in the imines carries no hydrogenatom, as in 2,3,4,4a,5,6-hexahydro-4a-methylbenzoh-quinoline (VIII; Me in place of OH).l5EXPERIMENTALN.1n.r. spectra were measured with a Varian T60 60 MHzspectrometer for solutions in 2Hchloroform unless other-wise stated, with tetramethylsilane as internal standard.Mass spectra were determined with a Hitachi RMU-6Lspectrometer at 80 eV by using the direct inlet system.3T.p.s were taken for samples in open capillaries in a sul-phuric acid bath. Petroleum refers to the fraction of b.p.60-80".Organic extracts were dried over anhydroussodium sulphate. The homogeneity of compounds waschecked by t.1.c. on silica gel.l3 E. G. Brain, F. Cassidy. M. F. Constantine, J. C. Hanson, andJ. D. Tidy, J . Chem. SOC. ( C ) , 1971, 3846.l4 R. C. Cambie and T. D. R. Manning, J . Chenz. SOC. ( C ) ,1968, 2603; R. C. Cambie, V. F. Carlisle, C. J. LeQuesne, andT. D. R. Manning, ibid.. 1969, 1234.l6 D. Nasipuri and S . K. Ghosh, unpublished data; see alsoref. 2.70.1; H, 7.0. Calc. for C1amp;amp;: C, 69.9; H, 6.8),v=(Nujol) 1 '700 cm-l.2-A cetyL 1,2,3,4-tetrahydro-6-nzethoxynaphthaZene (I) .-The foregoing acid (14.4 g, 0.07 mol) was treated with reflux-ing thionyl chloride (8 ml) for 4 h. Removal of thionylchloride, left the acid chloride as a crystalline solid, m.p.77".To a solution of diethyl ethoxymagnesiomalonatefrom magnesium (1.92 g, 0.08 mol), ethyl malonate (12.8 g,0.8 mol), absolute ethanol (17 ml), dry ether (50 ml), and adrop of carbon tetrachloride (to initiate the reaction) 18 theacid chloride (14.4 g) in ether (100 ml) was slowly added.The solution was kept refluxing during the addition anduntil i t became too viscous to be stirred. After cooling,the mixture was decomposed with dilute sulphuric acid,the ethereal layer separated, the aqueous solution onceextracted with ether, and the combined organic extractsdried and evaporated. The residue was hydrolysed with arefluxing mixture of concentrated sulphuric acid (4 ml),acetic acid (24 ml), and water (16 ml) for 5 h.The usualwork-up l8 afforded the ketone (I) (11.8 g), b.p. 160" a t 0.6mmHg (Found: C, 76.3; H, 7.9. C13H1602 requires C,76.5; H, 7.8), vmag (neat) 1712 cm-l, T (CCl,) 7.80 (s,MeCO) ; dinitrophenyl~y~razone (from methanol-ethyl ace-tate), m.p. 125" (Found: C, 59.1; H, 5.4; N, 14.5. Clo-H,,N40, requires C, 59.4; H, 5.2; N, 14.6).2-Furfurylideneacetyl- 1,2,3,4-tetrahydro-B-methoxynapk2-thaZene.-The ketone (I) (2.04 g, 0.01 mol) was condensedl6 J. Jacques and A. Horeau. Bull. SOC. claim. France, 1950,512.l7 R. D. Haworth, B. Jones, and Y . M. Way, J . Chem. Soc.,1943, 10; K. N. Campbell, J. A. Cella, and B. K. Campbell, J .Amer. Chem. SOC., 1953, 75, 4681.la G. A. Reynolds and C . R. Hauser, Urg. Synth., Coll. Vol.IV,1963, 7081892 J.C.S. Perkin Iwith 2-furaldehyde (1.2 g) in the presence of methanolic4 sodium methoxide (10 ml) . After 24 h at room temper-ature, the pale yellow crystals (2.7 g) were collected andrecrystallised from ethanol t o give light yellow Plafes,n1.p. 108" (Found: C, 76.7; HI 6.3. C1,H1,03 requires C,76.6; HI 6.4), vmx (Nujol) 1682 and 1 610 cm-l.4,7-Dioxo-7-( 1,2,3,4-tetrahydro-6-methoxy-2-naphthyl) he+tanoic Acid-The above furfurylidene derivative (2.4 g)was heated under reflux with concentrated hydrochloricacid (9 ml) and ethanol (40 ml) for 18 h. The tarry materialobtained after removal of ethanol was boiled with a mixtureof concentrated hydrochloric acid (25 ml), glacial aceticacid (30 ml), and water (65 ml) for 2-3 h.The hotsolution was filtered through glass wool and the filtrate wasset aside. The process was repeated several times and thecombined filtrates on cooling afforded the dioxo-acid (1.358). Recrystallisation from aqueous methanol gave whiteplates, m.p. 99-101" (Found: C, 67.5; HI 7.2. C,,H,,O,requires C, 67.9; H, 6.9~0), vmax. (Nujol) 1700-1 730brcm-1.5-oxo-2-( 1,2,3,4-tetrahydro-6-methoxy-2-na~hth~~Z)cyclo-pepzt-l-enylacetic Acid (11) .-The preceding dioxo-acid (1.2 g)was taken up in aqueous 2 potassium hydroxide (100 ml)and warmed at 95 "C for 1.5 h. The solution was cooledand acidified with concentrated hydrochloric acid. Thepale yellow crystalline solid obtained was filtered off,washed with water, and dried to give the acid (11) (1.07 g,95), m.p.170". Recrystallisation from methanol affordedpale yellow needles, m.p. 172-173" (Found: C, 71.9; H,0.8. C18H,o04 requires C, 72.0; H, 6.7), vmax. (Nujol)1 720 and 1 700 cm-l. The methyl ester, prepared by treat-ment with refluxing methanolic 3 hydrogen chlorideformed plates, m.p. 91" (methanol) (Found: C, 72.7;HI 7.3. C1,H,204 requires C, 72.6; H, 7.0y0), z 2.90-3.34(3 HI m, ArH), 6.17 (3 H, s, CO,Me), 6.27 (3 H, s, OMe),6.70 (2 H, s, CH,*CO,Me), 6.90-7.70 (9 H, m, 4 x CH, +CH), and 8.08 (2 HI m, 4-H,).tvien-1 l-oic Acid (III).-The above methyl ester (3.14 g) wasdissolved in methanol (50 ml) and shaken with 10 pal-ladium-charcoal (500 mg) in hydrogen. The catalyst wasremoved and the filtrate was treated with sodium methoxidefrom sodium (50 mg) and methanol (2 ml).The solventwas removed (steam-bath) and the residual gum (3.1 g) wascliromatographed over alumina. A main fraction (2.9 g)showing a single spot on t.1.c. was isolated. This washydrolysed by heating with ethanolic 10 potassiumhydroxide to furnish a keto-acid as a gum which, fromanalogy,7 was assigned the trans-structure (111) (Found :C, 71.3; H, 7.6. C,,H,,O, requires C, 71.5; H, 7.3y0),vIIm9. (CHC1,) 1 745 and 1 715 cm-l.{~)-3-Methoxy-9,17-dioxo-18-nor-9,1 l-secoestra-1,3,5( 10)-trien-ll-oic Acid (IV).-The keto-acid (111) (3.0 g, 0.01 mol)x i s dissolved in glacial acetic acid (11 ml) and a solution ofchromic acid (1.8 g, 0.01 6 mol) in acetic acid (6 ml) and water(0.8 ml) was added in portions during 4h with stirring andcooling (ice-water).The green solution was kept in therefrigerator overnight, then diluted with cold water, andthoroughly extracted with ethyl acetate. The gumobtained by removal of solvent was triturated with ether t ogive the tetralone derivative (IV) as a white solid (1.1 g)-Recrystallisation from ethyl acetate gave nodules (0.62 g,20), m.p. 188-189" (Found: C, 68.1; H, 6.5; M f ,W. E. Bachmann and D. G. Thomas, J . Amer. Chem. SOC.,1941, 63, 598.( amp;)-3-Methoxy- 17-oxo- 18-nor-9,l l-secoestra- 1,3,5( 10)-316. C,,H,,O, requires C, 68.4; HI 6.3; MI 316.), vmx.(KBr) 1 742, 1 712, and 1 670 cm-l, lH n.m.r. data in agree-ment with the structure.( f)-amp;Hydroxy-3-rnethoxy- 1 l-aza- 18-norestra- 1,3,5,9( 1 1) -tetraen-17-one (IX).-The keto-acid (IV) (0.41 g, 1.3 mmol)was dissolved in anhydrous acetone (60 ml) and cooled t o- 5 "C.Triethylamine (0.202 g, 2 mmol) was added undernitrogen, followed by ethyl chloroformate (0.217 g, 2 mmol),and the mixture was stirred in the cold for 30 min. Sodiumazide (0.195 g, 3 mmol) in water ( 1 ml) was dropped in andstirring was continued for 2 h at 0 "C. The mixture waspoured into ice-water t o precipitate the azide as a gum,which was taken up in chloroform and dried.The residue (0.41 g) left after removal of chloroform(during which partial decomposition of the azide tookplace) was heated in toluene (10 ml) on a steam-bath for1 h. Toluene was removed under reduced pressure and thecrude isocyanate (0.40 g) was boiled with a mixture of glacialacetic acid (3.5 ml) , concentrated hydrochloric acid (3.5 ml) ,and water (3.5 ml) for 20 h under nitrogen.The cooledsolution was diluted with water, extracted thoroughly withether, and then neutralised with aqueous lOyo sodiumhydrogen carbonate. The liberated gum was taken up inether and dried, and the solvent was removed. The residue(0.160 g) solidified on scratching and was adsorbed on analumina column. Elution with chloroform furnished awhite amorphous powder (136 mg), m.p. 134-138", whichwas recrystallised from benzene to give (amp;)-8-hydroxy-3-methoxy- 1 l-aza- 18-norestra- 1 , 3,5 ( 10) , 9 ( 1 1)-tetraen- 17-one(IX), m.p. 136-138" (Found: C, 71.5; H; 6.7; N, 5.1.C,,H,,N03 requires C, 71.6; HI 6.7; N, 4.9y0), vmax.(Nujol)3 500-3 200, 1 755, 1 740sh, 1 643w, and 1 610 cm-1, vmsx.(CHCl,) 3 500, 1760, and 1630 cm-l, amp;,. (EtOH) 209(log E 4.24), 225 (4.10), and 275 nm (4.06), T (100 MHz)2.00 (1 H, d, J 9 Hz, 1-H), 3.20 (1 H, 2d, J 9 and 3 Hz,2-H), 3.37 (1 HI d, J 3 Hz, 4-H), 6.04 ( 2 HI m, 12-H,), 6.18(3 H, s, OMe), 6.92 (1 H, m, 13-H), 7.22 (2 HI m, 6-H,),7.72 (2 HI m, 16-H,), 7.95-8.26 ( 5 HI m, 2 x CH, + CH),and 8.50 (1 H, s, OH, exchangeable with D,O).Acid.-Methyl 1,2,3,4-tetrahydr0-6-methoxy- l-oxonaphthalene-2-carboxylate was alkylated with ethyl y-bromobutyrateand the product hydrolysed t o furnish y-( 1,2,3,4-tetrahydro-6-methoxy- l-oxo-2-naphthy1)butyric acid (VII) , m.p. 102-103" 101.5-103").The oxo-acid (2.0 g) was reducedby heating with hydrazine hydrate (5 ml) , diethylene glycol(25 ml), and potassium hydroxide (1.8 g) (Huang-Minlonprocedure) to give the title acid as a crystalline solid (1.7 g)(from ether-petroleum), m.p. 69-70" (Found: C, 72.4;H, 8.3.Oxidation of y-( 1,2,3,4-Tetrahydro-6-nzethoxy-2-naphthyZ)-butyric Acid.-A solution of chromic acid (1.0 g) in aceticacid (3 ml) and water (1 ml) was added to the precedingtetralin derivative (0.8 g) in acetic acid (6 ml) with stirringduring 5 h. The green solution was left at room temper-ature overnight, then diluted with water, and the productwas worked up in the usual way to give the tetralonederivative (VII) (0.5 g), m.p. 10@-101", identical (i.r.spectra and mixed m.p.) with the previous sample.2,3,4,4a, 5,6-Hexahydro- 8-methoxybenzohquinolin-4a-ol(VIII).-The oxo-acid (VII) (2.0 g) was converted into theazide (1.56 g), m.p.45-55", and the latter decomposed andrearranged according to the procedure already describedt o furnish the benzohquinoZzne (VIII) as a crystallinesolid. Recrystallisation from chloroform afforded whitey-( 1 , 2, 3,4:-Tetrahydro- 6-methoxy-2-naphthyl) butyricCl,H2,O3 requires C, 72.6; H, 8.0)1976plates (1.0 g), m.p. 146-147" (Found: C, 72.5; H, 7.3;N, 6.3; M+, 231. C1,H1,NO, requires C, 72.7; H , 7.4;N, 6.1 ; M , 231), vmX. (KBr) 3 160, 1 640, and 1 600cm-l, lH n.m.r. data as expected.Oxidation of 3-Methoxyestra-1,3,5( lO)-trien-17-one (EstroneMethyl Ether) .-Estrone methyl ether was oxidised withchromic acid by a modified procedure.14 The ether (1.0 g)was taken up in glacial acetic acid (12 ml) and chromic acid(0.85 g) in acetic acid (6 ml) and water (2 ml) was added inthe cold during 4 h.The mixture was kept in the refriger-ator overnight, then diluted with water, and thoroughlyextracted with ether. The extract was shaken repeatedlywith aqueous sodium hydrogen carbonate. The alkalinesolution on acidification afforded a crystalline compoundwhich was filtered off and crystallised from ether to affordthe 9,17-dioxo-acid (V) (0.31 g, 27), m.p. 155-156"(lit.,14 m.p. 158") (Found: C, 68.7; H , 6.8; M+, 330.Calc. for C,,H,,O, requires C, 69.0; H, 6.7; M , 330),vmax. (CHCl,) 1 745, 1 710, and 1 675 cm-l.3-Methoxy- 1 l-axaestra-l,3,5( lo) ,9( 1 l)-tetraen- 17-one (X) .-The preceding oxo-acid (V) (0.66 g) was converted by aprevious procedure into its azide, m.p.137-145", and theninto the 1 l-azaestratetraenone (X) (0.425 g). This wasadsorbed on an alumina column, eluted with benzene, andfinally recrystallised from benzene-ether to give needles(0.28 g, 50), n1.p. 162-164" (Found: C, 76.3; H , 7.6;N, 5.174; M+, 283. C1,H,,NO, requires C, 76.3; H , 7.4,N, 4.9; M , 283), vmx. (Nujol) 1 730, 1 615, and 15902d, J 9 and 3 Hz, 2-H), 3.34 (1 H, d, J 3 Hz, 4-H), 6.11(2 H, q, J 8 Hz, 12-H,), 6.17 (3 H, s, OMe), 7.03 (2 H , m,6-H,), 7.38-7.67 (2H,m, 16-H,), 7.78 (3H, m, 15-H, + 14 +H), 8.22 (3 H, m, 7-H, + 8-H), and 9.06 (3 H, s, Me),Am= (EtOH) 260 (log E 4.03) and 270 nm (4.06).3-Methoxyestra-l,3,5( lO)-trien- 17-02.-Estrone methylether (5 g) was dispersed in methanol (150 ml) and to i tcm-1, (100 nmz) 1.92 (1 H, d, J 9 HZ, i - ~ ) , 3.20 (1 H,sodium borohydride (2.5 g) was added in one portion.After being stirred at room temperature for 1 h, the mixturewas refluxed for 1 h, cooled, and decomposed with ice-water.The solid was filtered off and recrystallised from aqueousethanol to give the 17-01 (4.8 g), m.p.122" (lit.,zO 120-121") ;acetate, m.p. 102" (lit.,20 101-102.5").3-Methoxy-1 l-azaestra-1,3,5( 10),9( 1 lj-tetraen-17P-oZ (XI).-The above acetate was oxidised with chromic acidto the oxo-acid (VI), m.p. 146" (lit.,14 141-143") accordingto the procedure of Cambie et The oxo-acid (VI)(1.12 g) was submitted to Curtuis reaction as alreadydescribed giving successiveIy the azide, m.p. 73", and the11-azaestratetraenoz (XI) (0.65 g). The latter was adsorbedon an alumina column, eluted with benzene-ethyl acetate(9:1), and finally crystallised from ethyl acetate to giveplates (0.42 g, 50), m.p. 225-227" (Found: C, 75.5;H, 8.3, N, 5.2; M+, 285. C,,H,,NO, requires C, 75.5;H, 8.1; N, 4.9, M , 285), vmX (Nujol) 3 100, 1600, and1575 cm-l, 7 (100 MHz) 1.98 (1 H, d, J 9 Hz, 1-H), 3.15( l H , d , J9Hz,2-H),3.33(1H,s,4-H),6.ll(SH,m,12-H,),6.17 (3 H, s, OMe), 6.50 (1 H , t , J 15 Hz, 17-H), 7.08 ( 2 H,m, 6-H,), 7.67-7.90 (3 H , m, CH, + CH), 8.11 (1 H, s,OH), 8.33-8.61 (5 H, m, 2 x CH, + CHI, and 9.20(3 H, s, Me).We thank Dr. U. Eder, Schering AG, Berlin 65, for a giftof estrone methyl ether, Dr. U. R. Ghatak, Indian Associ-ation for the Cultivation of Science, and Dr. D. N. Roy,Faculty of Forestry, Toronto University, for n.m.r. spectra,and Dr. E. Ali, Indian Institute of ExperimentaI Medicine,for help with mass spectra. One of us (S. K. G.) is gratefulto the Council of Scientific and Industrial Research, NewDelhi, for a fellowship.6/405 Received, 1st March, 197612O M. Levitz, J . Amer. Chem. Soc., 1953,75, 5352
展开▼
