Steroid Analogues. Part 2. Synthesis of Unsymmetrical Bi(cycloalky1- id e n e )s via vic-Dinitro-co m poun d s By David J. Humphreys, (Mrs.) Pamela M. Lawrence, and Christopher E. Newall,’ Organic Chemistry Department, Glaxo Research Ltd., Greenford, Middlesex UB6 OH E The light-catalysed reaction of 4,4-dinitrocyclohexanol (6) with the lithium salts of 4-substituted 1 -nitrocyclo-hexanes [4-0Bz (4). 4-CH,C02Me (1 Z), 4-CH2COMe (1 5). and 4-H (1l)]gave 4’-substituted 4-hydroxy-1 ,l’-di- nitro-1 ,l’-bicyclohexyls (16). Irradiation of the latter in the presence of sodium sulphide in dimethylformamide gave 4‘-substituted 4-hydroxy-1.1 ’-bi(cyclohexy1idene)s (17)-(21) in overall yields of 29-70%. Condensation of (*)-6~-methyl-3,3-dinitro-rrans-bicyclo[4.3.0] nonan-7P-01 (31 ) with the lithium salt of 4-benzoyloxy-1 -nitrocyclohexane (4) gave in 12% yield a 1 : 1 mixture of the epimeric (*)-3~,17~-dihydroxy-6,7-dinor-5.8-seco-estr-9-enes (33).IN the preceding paper we describe the preparation of bicyclic intermediates that could serve as the pre- cursors of rings c and D in our projected series of 6,7-dinor-5,8-seco-As-steroids.In this and subsequent papers 2-4 we describe the various methods used to attach a ring A synthon to these intermediates. Kornblum and his co-workers 5-7 recently described a synthesis of cycloalkylidenecycloalkanesby a two-stage process involving coupling of nitro-compounds ; the light-catalysed condensation of a gem-dinitroalkane with the lithium salt of a nitrocycloalkane in dimethyl sulphoxide gave a vic-dinitro-compound that, on irradi- ation in dimethylformamide in the presence of sodium sulphide, yielded the desired olefin in high yield.The first stage can also be carried out in dimethylform- amide,8 making possible a ‘ one-pot ’ process. We planned first to confirm that this method was compatible with the presence of oxygen-containing functional groups by the synthesis of a number of substituted bi(cyclohexy1idene)s that were of interest to us in their own right, and then to extend it to the preparation of the desired tricyclic compounds. A mixture of the lithium salt of 4-nitrocyclol?exyl benzoate (4), prepared by oxidation of the corresponding oxime (2) with trifluoroperacetic acid,s and 1,l-dinitro-cyclohexane was irradiated in dry dimethyl sulphoxide to give, in Myo yield, a mixture of the epimeric vic-dinitro-compounds (8).Crystallisation from hot acetone Part 1, D. J. Humphreys, C. E. Newall, H. A. Paskins, and G. H. Phillipps. preceding paper. * D. J. Humphreys, P. M. Lawrence, C. E. Newall, G. H. Phil-lipps, and P. A. Wall, following paper. I>.J. Humphreys and C. E. Newall, J.C.S. Perkin I, 1978, 33. I>. J. Hurnphreys, C. E. Newall, G. H. Phillipps, and G. A. Smith, J.C.S.Pprkin I, 1978, 45. K. Kornblum, S. F. Boyd, H. W. Pinnick, and R. G. Smith, J. -4wer. Chem. Soc., 1971, 93, 4316. afforded a single pure isomer (14%) which, on irradiation in the presence of sodium sulphide in dimethylformamide, yielded a mixture of 4-hydroxy-l,l’-bi(cyclohexylidene) (17) (71%) and the corresponding benzoate (9) (9%).Hydrolysis of 4-nitrocyclohexyl benzoate (4) with 2 equiv. of sodium hydroxide, followed by treatment with silver nitrate and sodium nitrite,1° gave 4,4-dinitro- cyclohexanol (6) (42%), which was oxidised to the ketone (7) with Jones reagent. Irradiation of a mixture of (6) and the lithium salt of nitrocyclohexane in di- methyl sulphoxide gave the dinitro-compound (16; R = H) in 24% yield after recrystallisation of the total product. A similar condensation was conducted in dimethylformamide and the uic-dinitro-compound (16; R = H)was reduced directly to the olefin (17) in 707k overall yield by addition of sodium sulphide to the reaction mixture and further irradiation. Condensation of 4,4-dinitrocyclohexanone(7) with the lithium salt of nitrocyclohexane in dimethylformamide and direct reduction of the intermediate, as above, gave only 5% of the desired 1,1’-bi(cyclohexyliden)-4-one (10).We believe that the poor yield was due to proton- ation of the nitro-salt by the enol form of the ketone. This coupling process was next used to prepare bi- (cyclohexy1idene)s bearing substituents in each ring. A solution of 4,4-dinitrocyclohexanol (6) and 4-nitrocyclo- hexyl benzoate (4) in dimethyl sulphoxide was treated with n-butyl-lithium (2 equiv.) and irradiated in the N. Kornblum, S. D. Boyd, and F. W. Stuchal, J. Amer. Chem. SOC.,1970, 92, 5787. N. Kornblum and S. I). Boyd, J.Amer. Chem. Soc., 1970, 92, 5788.* G. A. Russell, 33. K. Norris, and E. J. Panek, J. Amer. Chem. Soc., 1971, 93, 5839. W. D. Emmons and A. S. Pagano, J. Amer. Chem. SOC.,1955,77, 4557. lo R. B. Kaplan and H. Schechter, J. Amer. Chem. Soc., 1961, 83, 3535. usual way. Reduction of the total crude product with sodium sulphide under irradiation gave 4,4'-dihydroxy- 1,l'-bi(cyclohexy1idene) (18) in 29% yield (purity by g.1.c. 83.5%) ; comparison with authentic samples * of the cis- and trans-diols (18) showed that this material (1) R = Bz,X = 0 (4) (2)R = Bz,X = NOH (3)R = H,X = NOH (4)R = OBz (11) R = H (12)R = CHzC02Me (13) R = CHzCH(0Ac)Me (14)R = CHzCH(0H)Me (15)R = CH2COMe was a 1 :1 mixture of the two isomers.This lack of stereoselectivity is in keeping with Kornblum's evi-dence 5y7 in favour of a radical-anion mechanism for both coupling and reduction steps. The synthesis of the bi(cyclohexy1idene)s (19) and (21) was next examined; these two compounds can be regarded as bicyclic analogues of an androstane-17-carboxylic acid and a pregnan-20-one, respectively. OR J.C.S. Perkin I which was oxidised to methyl 4-nitrocyclohexylacetate (12). A mixture of the ester (12), 4,4-dinitrocyclo- hexanol (6), and 2 equiv. of lithium methoxide was irradiated in dimethyl sulphoxide. Reduction of the resulting vic-dinitro-compound with sodium sulphide in (7) (17)R = H (18)R = OH (19) R = CHzCOzH (20)R = CH2C02Me (21 ) R = CH2COMe dimethylformamide under irradiation afforded a mixture of the acid (19) (18%) and its methyl ester (20) (30%).4-Methoxyphenylacetone was converted by successive Birch reduction, acidic hydrolysis, and catalytic hydro- genation into the hydroxy-ketone (25). Acetylation of the latter, followed by reaction with hydroxylamine, furnished the oxime (27), which was oxidised to the nitro-ester (13). Mild acidic hydrolysis of the latter and subsequent oxidation gave 1-acetonyl-4-nitrocyclo-hexane (15), which was condensed with 4,4-dinitrocyclo- I hexanol (6) in the usual manner to give the desired mCH2CHMe xA0J xw enone (21) in 57% yield. (22)X = O,R = H (25) X = O,R = H (23)X = O,R = Me (26) X = O,R = AC (24)X = NOH,R = Me (27) X = NOH,R = Ac Birch reduction of 4-methoxyphenylacetic acid, followed by hydrolysis and catalytic hydrogenation of the product, gave 4-oxocyclohexylacetic acid l1 (22).The methyl ester (23) was converted into the oxime (24), Condensations involving bicyclic nitro-compounds met with less success. The hydroxy-ketone (28) was con- verted into the oxime (29) and thence into the nitro- compound (30). The lithium salt of (30)was irradiated in the presence of 4,4-dinitrocyclohexanol(6)in dimethyl sulphoxide, and the crude product was reduced with sodium sulphide in dimethylformamide under irradiation. The product was a complex mixture in which none of the l1 H. E. Ungnade and F. V. Morris, J. Amer. Chem. SOC., 1948, 70, 1898. desired olefin (33) was detected; however, a small amount of the hydroxy-ketone (28) was isolated.The transformations leading to the regeneration of this ketone are not clear; it is possible that a salt of the nitro-compound (30) underwent a Nef reaction during isolation. Alternatively, (30) may have been reduced by sodium sulphide in a manner analogous to the recently reported l2 reduction of nitro-alkanes by titanium(11) chloride. Following this failure, the nitro-compound (30) was converted into the gem-dinitro-compound (31). Con-densation of the latter with the lithium salt of 4-nitro-cyclohexyl benzoate (4) in the usual manner again gave a complex mixture, from which the desired olefin (33) was isolated in 12.5% yield. G.1.c.showed that this material was a 1 : 1 mixture of two components; com-parison with authentic (-j-)-3a,17p-dihydroxy-6,7-dinor-5,8-secoestr-9-ene, prepared by another route,4 confirmed that the product was a mixture of the 3a-and 3p-epimers of the diol (33). OH (28) X = 0 (29) X = NOH OH I The overall yield of (33)from the hydroxy-ketone (28) was only 2.3% ; thus, Kornblum's coupling procedure was not an attractive proposition for the synthesis of seco-steroids for biological evaluation. Subsequent work was therefore based on other, more efficient methods which were concurrently under investigation in our laboratories. EXPEKIMEXTAL For preamble see preceding paper. 4-( 2-AcetoxypropyZ)cycZohexanone (26) .-A solution of 4-(2-hydroxypropyl)cyclohexanone(25) (25 g, 160 mmol) in anhydrous pyridine (150 mi) and acetic anhydride (151 ml) was set aside at 20 "C for 18 h.The mixture was evaporated and the residue was mixed with toluene then re-evaporated, then partitioned between water and di-chloromethane. The organic phase was dried and evapor- ated to an oil (29.5 g, 93%). A small portion (150 mg) was purified by p.1.c. (CHC1,) to give the acetoxy-ketone (26) (104 mg), v,~,,~. 1 720 (ester) and 1 712 cm-l (GO),T 8.77 (3 H, d, J 6 Hz, CH,), 7.95 (3 H, s, OCOCH,), and 4.92 l2 J. E. McMurry and J. Melton, J.Amer. Chem. SOC.,1971, 93, 5309. (1 H, m, CHOAc) (Found: C, 66.5; H, 9.05. C11H18O3 requires C, 66.6; H, 9.15%). The crude product was sufficiently pure for conversion into the oxime (27).Prefiaration of 0ximes.-The ketone in ethanol was treated with an excess of hydroxylamine hydrochloride and sodium acetate in water and the mixture was stirred under reflux until the reaction was complete. Dilution of the mixture with water afforded the oxime, which was collected by filtration or extracted into dichloromethane. 4-Benzoyloxycyclohexanone oxime l3 (2) was obtained in 96% yield from 4-benzoyloxycyclohexanone l4 (1); it gave (from aqueous ethanol) crystals, m.p. 99-102', wnlaX. 3 570 and 3 280 (OH) and 1 710 cm-l (ester), T 4.69 (CHO-COPh). ( &)-7 p-Hydroxy- 6P-methyl- trans-bicyclo C4.3. Olnonan- 3-one oxzme (29) was obtained from the hydroxy-ketone (28) as an off-white froth (99%) which, on treatment with ether, yielded off-white prisms (25%).Recrystallisation from ether-methanol (4 : 1) gave a pure sample of a single isomer as prisms, m.p. 160-161", vmx. 3 595 (OH) and 1650w cm-l (C=N), T 9.22 (3 H, s, CH,) and 6.5 (1 H, m, CHOH) (Found: C, 65.7; H, 9.45; N, 7.3. C,,,H,,NO, requires C, 65.55; H, 9.35; N, 7.65%). The mother liquors were OH OH (31 1 HO (32) combined and evaporated to give crude oxime which was suitable for conversion into the nitro-compound (30). 4-MethoxycarbonyZmethylcyclohexanone oxime (24) was obtained in 95% yield from methyl (4-oxocyclohexyl)- acetate (23) as a yellow oil, v,,,. 3 590 and 3 285 (OH), 1728 (ester), and 1660w cm-l (C=N), T 6.31 (CO,CH,) (Found: C, 58.2; H, 8.2; N, 7.2.CgH1,NO, requires C, 58.35; H, 8.15; X, 7.55%). 4-(2-AcetoxypropyZ)cyclohexanoneoxzme (27) was obtained in quantitative yield from the ketone (26) as an oil. A small portion (200 mg) was subjected to p.1.c. to give the pure oxime (27) (140 mg), vmax. 3 595 (OH), 1 720 (ester), and 1660w cm-l (C=Tc'), T 8.80 (3 H, d, J 6 Hz, CH,), 7.98 (3 H, s, OCOCH,), and 4.95 (1 H, m, CHOAc) (Found: C, 61.9; H, 8.8; N, 6.1. Cl,HlgNO, requires C, 61.95; H, 9.0; N, 6.6%). The crude product was sufficiently pure for conversion into the nitro-compound ( 13). 4-Hydroxycyclohexanone oxime (3). A solution of 4-benzoyloxycyclohexanone oxime (2) (500 mg, 2.14 mmol) in ethanol (15 ml) and water (30 ml) was heated under reflux for 30 min with aqueous 2~-sodium hydroxide l3 A.Mooradian, U.S.P. 3 558 667 (Chem.Ah.. 1971, 75, P 20176 p). l4 E. R. H. Jones and F. Sondheimer, J.Chem.SOC.,1949, 615. (1.5 ml). When cool, the mixture was diluted with water (100 ml) and continuously extracted with chloroform for 20 h. The chloroform was dried and evaporated and the residue (250 mg, 90%) was crystallised from ether-petrol to give the oxime (3) (153 mg, 55%) as plates, m.p. 77-79" (Iit.,l5 78-79'), vmaX, 3 585 and 3 300 cm-l (OH), T 6.00 (CHOH) (Found: C, 56.0; H, 8.5;. N, 10.8. Calc. for C,H,,NO,: C, 55.8; H, 8.6; N, 10.8%). 4-NitrocycZohexyZ Benzoate (4) .-A solution of trifluoro-peracetic acid was prepared by addition of 86% hydrogen peroxide (0.60 ml, ca. 20 mmol) to a stirred solution of trifluoroacetic anhydride (3.4 ml, 24 mmol) in acetonitrile (5 ml).This solution was added over 40 min to a mixture of 4-benzoyloxycyclohexanone oxime (2) (2.33 g, 10 mmol), urea (200 mg), and disodium hydrogen phosphate (7.8 g) stirred at 80 "C. After a further 1 h at 80 "C the mixture was cooled and partitioned between water and ether. The organic phase was washed successively with aqueous 5% sodium hydrogen carbonate, aqueous 2 yosodium disulphite, and water, dried, and evaporated to a golden oil (2.28 g) . Chromatography over silica gel (dichloromethane as eluant) afforded the nitro-derivative (4) as a white waxy solid (1.425 g, 57y0), v,,,,. 1710 (ester) and 1548 and 1270 cm-l (NO,), T 5.50 (1H, m, CHNO,) and 4.80 (1 H, m, CHOCOPh) (Found: C, 61.65; H, 6.0; hT,5.5.Cl,Hl,1;0,,0.25H,0 requires C, 61.5; H, 6.15; N, 5.5%). ( -j-)-6p-MethyZ-3[-nitro- trans-bicyclo L4.3. Olnonan- 7p-01 (30).-By the above method, the oxime (29) (5.92 g, 32.3 mmol) gave the crude nitro-compound (30) as a golden oil (3.98 g). Chromatography over silica gel [eluting with dichloromethane-ethanol (24 : I)] afforded a golden gum (2.69 g, 42%), vmax. 3 620 (OH) and 1550 cm-l (NO,), T 9.10 (3 H, s, CH,), 6.30 (1 H, m, CHOH), and 5.60 (1 H, m, CHKO,) (Found: C, 60.1; H, 8.55; N, 6.75. Cl,H17N0, requires C, 60.3; H, 8.6; N, 7.05%). Methyl (4-NitrocycZohexy2)acetate ( 12) .-By the above method the oxime (24) (10.8 g, 58 mmol) yielded, after chromatography in dichloromethane over silica gel, the nitro-ester (12) as an oil (6.78 g, 54y0),vmax, 1 718 (ester) and 1 550 cm-l (NO,), T 6.29 (3 H, s, CO,CH,) and 5.52 (1 H, m, CHNO,) (Found: C, 53.9; H, 7.6; N, 7.1.C,,H,,NO, requires C, 53.7; H, 7.5; N, 7.0%). 1-1 2-A cetoxy~ropyZ)-4-nitrocycZohexane ( 13) .-By the above method the oxime (27) (900 mg, 4.22 mmol) afforded the crude nitro-compound (13) (630 mg). P.1.c. (CHCI,) yielded the nitro-ester (13) as an oil (280 mg, 29%), vmax. 1720 (ester) and 1546 cm-l (NO,), T 8.79 (3 H, d, J 6 Hz, CH,), 7.95 (3 H, s, OCOCH,), 5.60 (1 H, ni, CHNO,), and 5.00 (1 H, m, CHOAc) (Found: C, 57.6; H, 8.3; N, 5.9. C,,H1,NO, requires C, 57.6; H, 8.35; N, 6.1%). I-(2-HydroxypropyZ)-4-nitrocycZohexane (14).-A solution of the acetate (13) (16.0 g, 70 mmol) in methanol (50 ml) containing perchloric acid ( 12 drops of 60yo) was slowly distilled.The reaction volume was maintained by addition of methanol as necessary. After 7 h, the mixture was evaporated and the residue was partitioned between brine and dichloromethane. The organic phase was dried and evaporated to give the nitro-alcohol (14) as a yellow oil (12.8 g, 98%), v,,,, 3 630 (OH) and 1545 cm-l (NO,), T 8.81 (3 H, d, J 6 Hz, CH,), 6.10 (1 H, m, CHOH), and 5.55 (1 H, m, CHNO,) (Found: C, 57.6; H, 9.2; N, 7.3. C,H,,NO, requires C, 57.7; H, 9.1; pc', 7.5%). (4-NilrocycZohexyZ)acetone( 15) .-Jones reagent ( 15 nil) was added dropwise over 2 h to a solution of the nitro- alcohol (14) (11.6 g, 62 mmol) in acetone (300 ml) at 0 "C.J.C.S. Perkin I The mixture was stirred for a further 1 h, diluted with water, and extracted with ether. The extract was washed with water and evaporated with the aid of benzene to give the nitro-ketone (15) as a yellow oil (11.2 g, 98y0),v,,,. 1 711 (GO) and 1550 and 1382 cm-l (NO,), T 7.88 (3 H, s, COCH,) and 5.6 (1 H, m, CHNO,) (Found: C, 58.4; H, 8.1; N, 7.2. C,H,,NO, requires C, 58.35; H, 8.15; N, 7.55%). 4,4-DinitrocycZohexanoZ (6) .-A solution of 4-nitrocyclo-hexyl benzoate (4) (1.0 g, 4.01 mmol) in ethanol (40 ml) and water (60 ml) was heated under reflux with 2~-sodium hydroxide (4.1 ml) for 30 min. The solution was allowed to cool to room temperature and sodium nitrite (414 mg, 6 mmol) in water (10 ml) was added.The solution was then added to a rapidly stirred mixture of silver nitrate (1.4 g, 8.23 mmol), water (20 ml), ether (60 ml), and 2~- sodium hydroxide (2 drops) at 4 'C. A brown precipitate was formed immediately and the temperature rose to 10 'C. The precipitate gradually became darker and after 5 min the cooling bath was removed and the mixture was stirred for 30 min at room temperature, then filtered through kieselguhr. The residue was washed with ether and the filtrate was extracted with ether. The combined ethereal solutions were washed with water, dried, and evaporated. Crystallisation of the residue (521 mg, 68%) from ether- petrol gave 4,4-dinitrocycZohexanoZ (6) as off-white prisms (320 mg, 42y0), m.p. 109-llO', v,,,,. 3 610 (OH) and 1 570 cm-l (NO,), T 8.41 (1 H, s, OH), 5.91 (1 H, m, CHOH), 6.6-7.7 (4 H, m, 3-and 5-H), and 7.9-8.5 (4H, m, 2-and 6-H) (Found: C, 37.6; H, 5.3; N, 15.1.C,H,,N,O, requiresc, 37.9; H, 5.3; K, 4.75%). ( 5)-6~-MethyZ-3,3-dinitro-trans-bicycZoC4.3.01 nonan- 7p-OZ (31).-The nitro-alcohol (30) (870 mg, 4.37 mmol) in ethanol ( 10 ml) was treated with aqueous O.86~-potassium hydroxide (5.1 ml) and the nitro-salt was treated with sodium nitrite and silver nitrate as above. The crude product (915 mg, 86Oj,) was recrystallised from ether--petrol to give the dinitro-compound (31) as needles (500 mg, 47y0), m.p. 112-113', vmnx. 3 625 (OH) and 1575 cm-l (NO,), T 9.10 (3 H, s, CH,) and 6.28 (1 H, ni, CHOH) (Found: C,, 49.2; H, 6.55; N, 11.5. C,,H,,N,O, requires C, 49.2; H, 6.5; N, 11.450/,).4,4-DinitrocycZohexanone(7).-A solution of 4,4-dinitro-cyclohexanol (6) (2.0 g, 10.5 mind) in acetone (30 ml) was treated dropwise over 2 h with Jones reagent (2.6 ml). The mixture was stirred for a further 1 h, diluted with water, and extracted with ether. The 'extract was washed with water, dried, and evaporated to a waxy solid (1.87 g, 94%). A portion (750 nig) was subjected to p.1.c. (CH,Cl,) to give 4,4-dinitrocycloliexanone (7) as a white crystalline solid (510 mg, 64y0), m.p. 109-llO", vuws~1 730 (GO)and 1575 cni-l (SO,) (Found: C, 38.3; H, 4.3; N, 14.8. C,H,iC',O, requires C, 38.3; H, 4.25; S, 14.90/,). 4- Nitro-4- ( l-nitrocycZohexyZ)cyclohexyl Benzoate (8).-4-Sitrocyclohexyl benzoate (4)(074 mg, 3.9 mniol) in drq- methanol (20 ml) was treated with 1.7i~-lithiuni methoxide in methanol (2.32 nil, 3.95 mmol) and the solution was immediately evaporated to dryness under reduced pressure.The residue was dissolved in dry dimethyl sulphoxide (20 ml) and the red solution was degassed and stirred under nitrogen. 1, LDinitrocyclohexane (5) (680 mg, 3.9 mmol) in dry dimethyl sulphoxide (10 ml) was added and the mixture was irradiated for 2 h with eight 20 W ' Daylight ' fluorescent tubes. 0.1N-Hydrochloric acid (40 ml) and water (160 nil) were added and the mixture was stirred for l5 W. IT. Trager and A. C. Huitric, J. Phavm. Sci., 1967,56, 1111. 5 min, then stored at 0 "C for 1 h. The resulting pale green solid (1.265 g, 86%) was collected, washed with water, and recrystallised from acetone to give the vic- dinitro-compound (8) as prisms (219 mg, 15%), m.p.226- 232" (decomp.), v,,,. 1705 (ester) and 1545 cm-l (NO,), T (CF,.CO,H) 4.90 (1 H, m, CHOCOPh) (Found: C, 60.6; H, 6.4; F,7.5. C,,H2,N2O, requires C, 60.65; H, 6.45; N, 7.4504). 4-Hydroxy-( 17) and 4-BenzoyZoxy-l,l'-bi(cyclohexyZidene) (9).-A solution of the vic-dinitro-compound (8) (2.7 g, 7.25 mmol) in dimethylformamide (50 ml) was treated with finely ground sodium sulphide nonahydrate (4.3 g, 17.95 mmol) and tlie stirred solution was irradiated under nitrogen for 5 h with eight 20 W fluorescent tubes, then partitioned between water and dichloromethane. The organic phase was washed with water, dried, and evapor- ated.P.1.c. of the residue yielded as the less polar fraction a white solid (888 mg, 39%) which crystallised from ether- petrol to give the benzoate (9) as rods, m.p. 75-76", wmax. 1 708 cm-' (ester), T 4.80 (1 H, m, CHOCOPh) (Found: C, 79.1; H, 8.4. C,,H,,0,,0.25H20 requires C, 79.1; H, 8.5%). The more polar fractim (500 mg, 3804) crystallised from ether-petrol to give the alcohol (17) as needles, m.p. 115", vmax. 3 610 cm-l (OH), T 6.15 (1H, m, CHOH) (Found: C, 79.6; H, 11.5. C,,H,,O requires C, 79.9; H, 11.2%). 4-Nitro-4-(l-nitrocycZohexyZ)cycZohexanoZ (16; R = H).-Kitrocyclohexane (1.36 g, 10.54 mmol) was treated as above with methanolic lithium methoxide (10.75 mmol) and the resulting nitro-salt was irradiated for 6.5 h in dimethyl sulphoxide with 4,4-dinitrocyclohexanol (6) (2.0 g, 10.54 mmol).The product (1.9 g, 66q4) was crystallised from ether-dichloromethane to give the vic-dinitro-compound (16; R = H) as off-white prisms, m.p. 202-204", vmax, 3 605 and 3 400 (OH) and 1 550 cm-l (NO,), T 7.40 (Me,SO) and 6.50 (1 H, m, CHOH) (Found: C, 51.0; H, 7.3; N, 9.6; S, 2.4. C,,H,,N20,,0.25Me2SO requires C, 50.9; H, 7.5; N, 9.i; S, 2.7%). Irradiation of the product with sodium sulpliide in dimethylformamide, as above, afforded 4-hydroxy-l,l'-bi(cyclohexylidene)(17) (36%). Condensation of Nitrocyclohexane and 4,4-Dinitrocyclo-hexanol in 1)iinethylformamide. --Nitrocyclohexane (680 mg, 5.27 nimol) in dry methanol (12 ml) was treated with 1.8N-lithiuni rnethoxide in methanol (3.36 ml, 5.37 mmol) and the solution was evaporated to dryness.4,4-Dinitro-cyclohexanol (6) (1.0 g, 5.27 mmol) in dimethylformamide (60 ml) was added and the stirred mixture was degassed and irradiated under nitrogen for 6 h as above. Finely ground sodiuni sulphide nonahydrate (3.8 g, 15.8 mmol) was added and irradiation was continued for a further 4 h. The mixture was partitioned between water and dichloro- methane and the organic phase was washed with water, dried, and evaporated. Chromatography of the residue over silica gel yielded 4-hydroxy- 1, 1'-bi(cyclohexy1idene) (17) (670 mg, 70q4). l,l'-Bi(cyclohexyZiden)-4-one ( 10) .-Nitrocyclohexane (681 mg, 5.32 nimol) was converted into its lithium salt and irradiated for 7.5 h in dimethylformamide with 4,4-dinitro- cyclohexanone (7) (1.0 g, 5.32 mmol).Sodium sulphide nonahydrate (3.8 g, 15.8 mmol) was added and irradiation was continued for 2 h. Work-up as above yielded a brown gum (690 nig) which was subjected to repeated p.1.c. (CH,CI,) to give the ketone (10) (51 mg, 5%) as a gum, wllWx. 1 700 cm--l (GO), T 7.0-8.0 (12 H, m, 2-, 3-, 5-, 6-, 2'-, and 6'-H) and 8.1-8.7 (6 H, m, 3'-, 4'-, and 5'-H), for which a correct elemental analysis was not obtained. 23 4,4'-Dihydroxy-l, l'-bi(cycZohexyZidene) (18).-A stirred solution of 4,4-dinitrocyclohexanol (6) (380 mg, 2 mmol) and 4-nitrocyclohexyl benzoate (4) (498 mg, 2 mmol) in dry degassed dimethyl sulphoxide (20 ml) was treated under nitrogen with n-butyl-lithium in hexane (1.6 ml of 3~;4.8 mmol) and irradiated for 2 h as above.The mixture was then poured into water, acidified, and extracted with dichloromethane. The extract was washed with water and evaporated to a brown oil which was irradiated under nitrogen for 2 h in dimethylformamide (20 ml) containing sodium sulphide nonahydrate (2.4 g, 10 mmol) . Work-up as above gave a brown solid (240 mgj which was subjected to p.1.c. (CH,Cl,-MeOH, 19 : 1) to give the diol (18) (113 mg, 29%). Comparison of this material by t.1.c. with the pure cis-and trans-isomers of (18) showed that it was a 1 : 1 mixture of the two isomers. 4-AcetonyZ-4'-hydroxy- 1, 1'-bi(cycZohexy1idene) (21) .-1- Acetonyl-4-nitrocyclohexane (15) (555 nig, 3 mmol) was converted into its lithium salt as described above and irradiated under nitrogen in dimethyl sulphoxide containing 4,4-dinitrocyclohexanol (6) (570 mg, 3 mmol).After 3.5 h more lithium methoxide (3.1 mmol) was added and irradiation was continued for a further 1.5 h. The usual work-up gave the crude vic-dinitro-compound, which was irradiated along with sodium sulphide in dimethylform- amide for 2 h. The crude product (650 mg) was purified by p.1.c. (CHC1,-EtOAc, 5: 1) to give a solid (410 mg, 58y0),which was crystallised from ether-petrol to give the olefin (21) as needles, m.p. 116-125', wmX. 3 615 (OH) and 1710 cm-l (GO), T 7.74 (3 H, s, CH,) and 6.20 (1 H, m, CHOH) (Found: C, 75.0; H, 10.0. C1,H240,,0.25H20 requires C, 74.8; H, 10.25%).4-Hydroxy-4'-methoxycarbonyZmethyl-1, 1'-bi (cyclohexyl- idene) (20) and 4-CarboxymethyZ-4'-hydroxy-1, 1'-bi(cycZo- hexylidene) ( 19) .-The reaction of 4,4-dinitrocyclohexanol (6) (570 mg, 3 mmol) with methyl (4-nitrocyc1ohexyl)- acetate (12) (604 mg, 3 mmol) proceeded exactly as in the previous experiment. The mixture was partitioned be-tween water and dichloromethane, and the organic phase was washed with water, dried, and evaporated to a gum (130 mg). The combined aqueous phases were acidified and extracted with dichloromethane. The extract was washed with water, dried, and evaporated to a solid (650 mg). The combined products were subjected to p.1.c. (CHC1,-EtOAc, 2 : 1) to give as the less polar fraction the ester (20) (50 mg, 7%), m.p. 106-llO", wmax. 3 620 (OH) and 1728 cm-l (ester), T 6.35 (3 H, s, CH,) and 6.20 (1 H, m, CHOH) (Found: C, 68.9; H, 9.4. C1,H240,,0.5H20 requires C, 68.95; H, 9.6%). The more polar fraction (310 mg, 43%) was crystallised from acetone-petrol to give the acid (19) (50 mg, 7%), m.p. 162-166", v,,,. 3 600 and 3600-3200 (OH), and 1730 and 1710 cm-l (CO,H), 7 3.50br (1 H, m, C0,H) and 6.25(1 H, m, CHOH) (Found: C, 69.4 ; H, 9.1. C14H,,0,,0.25H,0 requires C, 69.25 ; H, 9.3%). ( f)-6,7-Dinor-5,8-secoestr-g-ene-3~,17p-dZol (33) .-The reaction between the dinitro-alcohol (31) (350 mg, 1.43 mmol) and 4-nitrocyclohexyl benzoate (4) (357 mg, 1.43 mmol) was carried out as in the previous two experiments. P.1.c. (acetone-petrol, 1 : 4) furnished the olefin (33) (120 mg) contaminated with the hydroxy-ketone (28). This material was stirred rapidly with ether and aqueous 1004 sodium disulphite for 45 min. Evaporation of the ethereal solution yielded the olefin (33) (45 mg, 12.5%), identical (i.r.,n.m.r., and g.1.c.) with the authentic 3P-i~omer.~ [7/1073 Received, 21st June, 19771