attempt's to effect the eliiiiiiiation of t'he tosylat'e group froni this mat'erial were unsuccessful and thus the projected pathway was not investigated further. How- ever, X I could be quite readily prepared from its 4,5- dihydro derivat'ive T'I through low temperature bro- mination followed by collidiiie-dimet'hylforniainide treatment of tlie iiiterniediate XIII. By application of tlic bromohydrin sequence, XI was easily converted to 17a-liydroxypregua-4,l l-diene-3,20-dione (XIV). The latt,er was also obtained froni YII through the 4p- bronio intermediate XT7."

Iuvestigation of the direct introduction of a hy- droxyl group a t C-17 through t'he procedure outlined by 13arton and co-workers12-13 was also pursued. In this series of reactions, pregn-1 l-ene-3,20-dione (XVI) was first converted to its diniet,liyl ketal XT'II through the sclenium dioxideemethanol technique14 or more con- veniently throiigli the use of p-toluenesulfonic acid- methanol. l 5 When the oxygenat'ion of XVII in the presence of potassium t-butoxide was conducted a t rooni temperature employing an excess of oxygen, with subsequent reduction of the intermediate hydroper- oxide, only trace aniouiits of hydroxylated materials were eiicountered and these results were quite variable. However, employing the reaction conditions more recently described by Amiard and co-workers,16 which emphasized lower reactioii temperature (ca. - 7 " ) , the desired 17 a-hydroxypregn- 1 l-ene-8,20-dione (VII) could be obtained consistently in a fair yield (58%).17 Thus direct hydroxylation provided t'he most con- venient route for the preparation of a 17a-hydroxylated substrate. Our attention was now directed toward the synthesis of the title conipounds from the advanced intermediate T7I.

The acetylation of T'II employing acetic anhydride- acetic acid-p-toluenesiilfonic acid afforded a crude enol diacetate XVIIIa which alt'hough isolated, was char- acterized only by spectral analysis. Careful basic methanolysis afforded the desired 17a-acetoxypregn-11- ene-3,20-dione (XTXI), but other hydrolytic condi- tions, although very mild, usually converted the eiiol diacetate into t!ie starting material VII. la

(11) Lithium chloride'9 deiiydrolialoaenation of XI11 gai'e 168-cl1l01~- 17a-11y~1roxypregns-4.1l-diene-3,20-dione (7.) I I I . ~ . 209-210°; lalu + 6 7 O (chloroform): A,,, 238 mp (t 14.800): I , , , 3300, 30.50. 29.50, 173.7, 166.5. 1625, 13.55, 1285, 1248, 751, and 718 C I ~ . - ' . Anal . Calcd. for CvH~zCIO,,: C, 69.50; H, 7..50; CI, 9.77. Found: C 69.40; H , 7 . 7 3 : Cl, 9.98.

Tile epoxide XI could be obtained f r r in i the rliloruhydrin (\.) on refluxina uitl i l iotassium acetate in aretone.

XI11 - LiCl &i; % X I

0 V

Bziley. ,J, Elks. and n. Barton. I'roc. C h r m . SOC., 211 (1960). Bailey, D. Barton, J. Elks. and J. Teiilpleton, J . C h e m . S u r . , 1.578

( l !J62) . (14) E. Olireto, C. Gerold. and E. Hrrsliberg. J . A m . Chem. Sor . , 76, 6113

(Ig.54). (15) 31. Janot, X. Lusinclii, and R. Goutarel, Bull. soe. c h i m . F i a n c e . 2109

( 1 $161 ). (16) G. Amiard, 31. Legrand, J . AIathieu. R. Heynier, and T. van Tlluong.

;bid., 2417 (1961). (17) I n the reduction of the intermediate 17a-hydroperoxide employing

zinc-acetic acid, the dimethyl ketal protective gtoup was consequently re- nioved.

(18) The relative ease of hydrolysis observed for the 17a-acetate grouping i i i a y possibly be ascribed to the absence of a Ila-axial hydrogen in the A"- wries.

The introduction of the a#-unsaturated ketone func- tion i n ring A presented no difficulty. The low tem- perature bromination of either XT'III or its enol di- acetate XI'IIIa afforded an excellent yield of 17a-acetoxy-4P-bromopregii-1 I-ene-3,20-dione (XIX). Elimination of the elements of hydrogen bromide using lithium chloride in dimethylforn~amide~~ afforded 17a-acetoxypregna--t, 1 l-diene-3,20-dione (XX) . Dehy- drogenation of the latter with 2,3-dichloro-5,6-dicyano- benzoquinone*" in refluxing dioxane gave the corre- iponding 1,4-dien-%one (XXI). This material could also be obtained by direct dehydrogenation of tlie saturated ring X ketone XT'III under similar reaction conditions. Conversion of XX to 17a-acetoxypregnx- 1,6, 1 l-triene-3,20-dione (XXII) was readily accoiii- plished utilizing the recent procedure of Ringold and Turner2' wherein XX in the presence of anhydrouq hydrogen chloride could be dehydrogenated i+ ith the quinone reagent to yield the 4,6-dieii-3-one X X I I directly. By the same procedure XIT' gave 17a- hydroxy pregiia-2,G,Il-trieiie-8,2O-dioiie (XXITI). I3y a two stage sequeiice, first introduction of the C-6,7- double bond and then the C-l,?-double bond. XX waq dehydrogenated to 17a-acetoxypregna-1,~,6, 1 l-tetra- ene-3,20-dione (XXIT').

The biological assay results for the various Al l -

compounds have been collected in Table I, along with those for 17a-acetoxypregn-4-ene-3,20-dione and 1701- a~etoxypregiia-1,4,6-triene-3,2O-dione.~~ These results indicate that the biological influence of a A"-doitblc> hond oil oral progestational activity i b varia'ile.

(19) R . Holysz, J . 4 m . C h e m . Soc., 76, 4432 (1933). (20) D. Burn, D. Kirk, and V. Petrow, P r o c . C h e m . Sor . , 11 (1960). (21) H. Ringold and A. Turner, Chem. Ind. (London). 211 (1962): cf.,

(22) J. P. Dusza, J. P. Joseph, and S. Bernstein, J . 0;~. Chem., 28, 92

(23) Assays were performed by Endocrine Laboratories, Madison, FTis-

R . Brown and L. .Jackman, J . Chem. Soc., 3144 (1960).

(1963).

consin.

3mi

1 '/"

\ I

V I I , R = R = H \ XVIII, R = Ac, R = H

XVIIIa. ~ ~ - 3 enol acetate XIX, R = A c . R -BY

0 --.,1-i"R / O&-iR /

XXII, R = A c XXIII , R = H XXIV, R = Ac, A'

XIV, R = H XX, R =Ac

l ~ l . l l \ \ . l l l . l . ' l 2

JuIY, 1963 A 1 1 - 1 7 ~ - A ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ASD RELATED COMPOCSDS 3G7

hr., then cooled and added t,o 2 ?; hydrochloric acid (7 I .) . The mixture was extracted n-ith chloroform and the extract was washed with water until neutral, dried, and evaporated leaving a dark gum. The latter was dissolved in ether (500 ml.) and washed with A' hydrochloric acid (100 ml.) and then water. Evaporat,ion of the dried solution gave a crude gum which was dissolved in benzene (100 ml.) and added to a column of silica gel (500 g , ) . Elution with benzeneether (98:2) gave 12.6 g. of crude IY, which on trituration with methanol afforded 11.3 g., 11i.p. 147-149.5°. Recrystallization from acetone-petroleum ether gave IV, m.p. 148.5-149.5": v m i x 2980, 1745, 1710, 1455, 1370, 1320, 1360, 1080, 1010 cm.-';

dnal. Calcd. for C?,H&: C, 71.61; H, 8.51. Found: C, 71.54; H, 8.56.

Further elution of the column with benzene-ether (9: 1) gave 4.6 g. of starting material (111), m.p. 172-175'.

The llp,l2a-dibromo derivative (IVa), prepared by bromi- nation a t 0" in :t methylene chloride solution, had m.p. 178-181"; [ a ] ~ +114" (c 0.35%); vmllr 2960, 17-18, 1710, 1470, 1370, 1265, and 995 cni.-l.

Anal . Calcd. for C?4H,4BraOj: C, 51.27; H, 6.09; Br, 28.42. Found: C, 51.02; H, 6.41; Br, 28.33. 16a,l7a-Epoxy-3a-hydroxypregn-ll-en-20-one (V).-.-A solu-

tion of 3a-carbethoxy-16a,l7~-epox~-pregn-l I-en-20-one (IV, 1.0 9.) in 0.1 S sodium iiiet,hoxide in methanol (60 ml.) was refluxed for 1 hr. It was then evaporated, and the residue !vas e Ctracted with methylene chloride. The washed and dried extract was evaporated leaving a semicrystalline solid which was crj-stallized from acetone-petroleum ether to give V 1711 nig.), m.p. 169- 170"; vmax 3540, 2940, 1710, 1690, 1370, 1080, 1015 em.-'; [alu +86" ( c 1.824).

dnai . Calcd. for C21H;juOu: C, 7 2 ; H, 9.15. Found: C, 76.19; H, 9.31.

16a,l7a-Epoxypregn -ene-3,20-dione (VI!.-To an ice-cold solution of 16a, 17a-epc -3a-hydrox>.pregn-ll-en-2O-one (V, 1.7 9.) in pyridine (36 ml.) s added a solution of chromium trioxide (1.62 g . ) in cold pyridine (18.7 rnl.). The resulting dark brown mixture was st,irred for 20 hr. a t room temperature, then methanol (about 50 nil.) was added. The solvents 1ver.e then evaporated to give a gum. Benzene was added and sub:equent,ly evaporated to remove the last traces of pyridine, The residue after the addition of water was extracted with methylene chloride and the extract' was washed successively with dilute sodium bi- carbonxte, and water. The dried meth>-lene chloride solution was passed through a column of l\Iagnes0!2~ and gave on evapora- tion the dione \-I (1.52 g.), m.p. 14:3-146'. Crystallization of a sample of this niaterial raised the m.p. to 147-149"; vmRX 2930, 1715, 1460, 1375, 1215, 1200 c m - l : [ a ] ~ +04" ( e 1.002).

a4nal. Cxlcd. for C r l H a 8 0 s : C, i ( j . 7 9 ; H, 8.59. Found: C, 76.60; H, 8.73.

16a,l7a-Epoxy-3a-hydroxy-l2a- tosyloxypregnan-20-one (VIII).-A solution of 3a-carhethoxy-l6a,17a-epoxy-12a-tosyl- oxypregnan-20-one (111, 1.0 9.) in 0.1 S niethanolic sodium meth- oxide (42 ml.) n-as refluxed for 0.5 hr. Evaporation in uucuo (bath temp. 25') gave a solid rezidue which Jvas partitioned be- tween water and meth!.lene rhloride. The organic layer was n-ashed with ir-ater until neutral, dried and evaporated in I ' U C U O . The addition of ether to the residue gave VI11 (0.88 g.), m.p. 174-1 76". Recrystnllization fronl acetonepetroleum ether did not alter the meking point; [ a ] u +75" (c 1,051); vmax 3470, Z 4 0 , 1695, 1605, 1365, 1355. 1175, 918 cm.-'.

.4nu/. Cdcd. for C&s06S: C, 66.91; H, 7.62; S, 6.38. Found, C, 66.57; H, 7.69; d, 6.60. 16a,17a~Epox~-12a-to3yloxypregnane-3,20~dione (PX).-To a

cw~!ed ( 0 -5') solution of rhromium trio.cide (1.23 g, ) in pyridine (15 nil.) there vas added a cold solution of 16a,l7a-epo,iy-3a-hy- d r11~y- l2~- tos~~ losypregnan-20-~~ne (VI I I , 2.0 g.) . The mixture \vas allo\\~ed to stand fur 15 min. a t 0" and then 3 hr. at room tem- perature when methanol 110 nil.) n as cautiousl). ildded, and the mixture was evaporated in cacuo. Benzene was added and the evaporatirm was repeated several times until th6 residual pyridine was removed. The residue was di.>solved in methylene chloride and washed with wat,er. The dried extract was passed through a column of J I a g n e s i ~ l ~ ~ to reniuve the dark colur and evaporated to afford crystalline I X (1.8 g.). A sample was recrystallized froni acetone-getroleurri ether and the n i . p remained unchanged

[ a ] ~ +87" ( c 1.130).

at 206-207'; [ a ] ~ $75' (c 0.907); vmnP 2850, 1710, 1605, 1335, 1175, 918 cm.-'.

Anal. Calcd. for C28H3606S: C, 67.18; H, 7.25; S, 6.39. Found: C, 67.35; H, 7.45; S, 6.59.

4p-Bromo-16~,l7~-epoxy-12~- tosyloxypregnane-3,2O-dione (XI.-To a cold (-60") solution of 16a,170-epoxy-l2~-tosylo:~y- pregnane-3,20-dione (IX, 0.4 g.) in chloroform (8.0 nil.) and ace- tic acid (0.9 ml.) there was added with stirring over a period of 45 min. bromine (0.041 ml.) in 32'2 hydrogen bromide-acetic acid (0.196 ml.), and acet,ic acid 10.6 nil.). The solution ir-tis then kept at -60" for 1 hr. ivhen a solution of sodium acetate (131 mg.) in water (1.1 ml.) was added. The mixture was stirred a t rnoni temperature for 0.5 hr. when chloroform was removed in sumo, and mater was added. The residua! mixture was cooled in an ice bath for 1 hr., and the white solid which formed was collected and dried. Recrystallization from acetone-petroleum ether gave X (409 mg.), m.p. 189-191" dec.; vlnZ, 2946, 1738, 1708, 1608, 1355, 1178 cni.-'.

.-lnai. Calcd. for ClaHosBrO C, 58.03; H, 6.08; Br, 13.79; Y. 5.53. Found: C, 57 , 57.:35; H, 6.15, 6.15; Er, 1'3.61; S, 5.76. 16a,l7a-Epoxy-12a-tosyloxypregn-4-ene-3,2O-dione (XII).--A

solution of S (1.25 g . ) in collidine (30 ml.) was refluxed for 6 hr., cooled, and the e-<cess collidine was removed in U ~ C U O (hath temp. 45-50"). The residue was dissolved in methylene chloride (50 nil.) and washed wit,h S hydrochloric acid 150 nil. 1 and then twice with water. rlft,er being dried the solvent n-as removed in cacuo; an infrared analysis of the crude residue indicated the tosyl group was still present but tha t dehydrohalogenat,ion had taken plare as shon-n by the conjugated ketone absorption. A Eolution of this crude residue in methylene chloride was filtered through :t pild of ~ l a g n e s 1 ~ 1 ~ ~ to remove color. Evaporntion of the niethyl- ene chloride in cac'uo gave a light yellow cryst:illine solid 1x11) (0.86 g.), m.p. 195-200'. A portion of this material, was crys- tallized from acetonepetroleum ether, m.p. 203-204": [a]u +l12" ( e 0.790); A,,,, 227 mfi ( c 23,400), 23s ni,u ( e 15,500); vms, 2960, 1710, 1665, 1620, 1605, 1350, 1185, 1175, 912 cin-l .

-inal. Calcd. for CZ~H,,O&~: C, 67.45; H, 6.87: S, 6.42, Found: C, 67.35, 67.58; H, 6.99, 7.35; 8, 6.58.

16a,l7a-Epoxypregna-4,ll-diene-3,20-dione (XI) . A.--A sn- lution of 4P-bromo-16~~~ 17a-epox~--12a-tosylo:~~pregnane-3,20-di- one (X, 0.1 g.) in collidine (1 ml.) n-as refluxed for 6 hr., and evaporated in uacuo. The residue was dissolved in methylene chloride and passed through a sinall colunin of .\Iagnesol.2g The crude residue after evaporation was triturated with cold ether to give S I (15 mg.), n1.p. 185-190'. This niaterial was identiVal with that obtained in procedure B.

B.-To a cold (-60") solution of lGa,l7a-epoxypregn-ll-ene- 3,20-dione (VI, 0.38 g . ) in methylene chloride (5.5 ml.)> chloro- form (5.5 nil.), and acetic avid (1.35 nil.) there was added over LZ

period of 20 inin., n i th stirring, bromine 10.038 nil.) in 307, hy- drogen bromide-acetic acid (0.29 ml.) and acetic acid (0.91 nil.), After 1 hr. a t -60" a solution of sodium acetate (0.19 g.) in water (20 ml.) was added and the mixture was stirred a t rooni temperature for 1 hr. The mixture was evaporated i n vacuo (bath temp., 30"), and the residue was treated with water to give a gum which partially crystallized. Identification of this material as 4@ - bromo - 1 6 4 7a -epoxypregn-1 l-ene-3,20-dione ( X I I I ) was based on an infrared analysis of t he carbonyl region which exhibited peaks a t 1690 and 17'20 This crude product (430 mg.) was dissolved in dimethylfornianiide (2.5 nil.) and collidine (1.0 nil.) and the solution was refluxed for 2.5 hr. After dilution with methylene chloride, the solution was washed with lvater, A \ hydrochloric acid, and then water and sodiuin bicarbonate. The dried methylene chloride solution was passed through MagnesolZ8 to give XI (0.30 g.) , m.p. 195-197". A recrystallization from ether gave ivhite crystals, 1ii.p. 203- 205"; A,,,, 238 niM ( e 15,000); on,,, :!040, 1625, 1380, 752, 7 2 2 em.-'; [ a ] ~ + l X l o (c 0.

Anal. Calcd. for C2,H?60a: C, 77.27: H. 8.03. Forind: C, 76.83; H, 7.84. 3.3-Dimethoxvore~n-ll-en-20-one IXVII). A.--A solution of _ - - , ,

pregn-1 l-ene-3,20-di0ne~~ (XVI, 18.0 g . ) and selenium dioxide (18.0 g.) in methanol (500 ml.) n-as dloived to stand at room tem- perature. After 0.5 hr. crystals began to separate. These were c.ollect,ed by filtration after 24 hr. and lr-ere washed with methanol

(80) "Elsevirrs Encyclopedia of Organic Chelliistry, ' Yol. 14 Sul,l lewent. Springer-Verlay Brrlin, I M Y PIJ. 2793-2794s .

July, 1963 A 1 l - l T ~ - S ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ASD RELATED COMPOUSDS 369

with ether. I n this manner there was obtained X I X (81 mg.), m.p. 173-174" dec. Crystallization from ether raised the m.p. to 178-179" dec.; [a]D +58' ( e 0.950); vmal 2940, 1735, 1370, 1265, 1250, 725 cm.-'.

Anal. Calcd. for C23H31Br0.,: C, 61.19; H, 6.93; Br, 17.72. Found: C, 60.92; H, 7.08; Br, 17.89.

17a-Acetoxypregna-4,ll-diene-3,20-dione (XX). A.-Under an atmosphere of nitrogen, crude 40-bromo-17a-acetoxypregn-11- ene-3,20-dione (SIX, 1.5 g.) and lithium chloride (2.8 g.) u-ere heated in dry dimethylformamide (50 ml.) for 3 hr. a t 100-110". The solvent was removed in ~ a c u o and methylene chloride vias added. The extract was washed with a saturated sodium bicarbonate solution and water, dried, and evaporated to give a yellow solid which was dissolved in benzene and added to a column of Florisi13' (50 g.) . Elution with 6YG acetonepetroleum ether gave 3 major fractions which were grouped according t o the results obtained by thin layer chromatographic analysis. Fraction A4 contained product contaminated with a less polar material which gave on crystallization from acetone-petroleum ether XX (107 mg.), m.p. 210-21lo. Fraction B was essentially pure XX, m.p.8216-2190. Fraction C contained XX with a inore polar substance and had a low m.p. Crystallization of a sample of fraction B from ether gave crystals: m.p. 220-222"; [ a ] ~ +123' ( e 1.160); A,,, 238 mu ( E 17,200); vInax 3010, 2930, l i30, 1660, 1620, 1445, 1360, 1265, 1250, 1072, 718 cm.-'.

Anal. Calcd. for C?,H3,04: C, 74.56; H, 8.16. Found: C, 74.50; H , 8.30.

B.-l7a-Hydroxypregna-4,1 l-diene-3,2O-dione (XIV, 0.83 g.) was dissolved in a mixture of acetic acid (25 ml.) and acetic anhy- dride (8 nil.), Kitrogen was bubbled into this solution for a f en min. and then p-toluenesulfonic acid (0.83 g.) was added and the reaction mixture was sealed for 18 hr. A yellow solid sep- arated when the reaction solution was poured into ice water and the precipitate was collected. r l methylene chloride solution of the latter was washed with water, dried, and evaporated. The resulting gum was dissolved in methanol (10 ml.) and a S sodium methoxide in methanol solution was added dropwise until the pH was 9-10, The solution was then refluxed for 15 min., neutralized with acetic acid, and evaporated to provide XX (552 mg.), m.p. 208-210", whose infrared analysis was in agree- nient with material obtained from procedure -4 above.

17.~-Acetoxypregna-l,4,ll-triene-3,20-dione (XXI). A.-A so- lution of crude 17cu-acetosypregn-ll-ene-3,20-dione (XVIII, 585 nig.) and 2,3-dichloro-5,e-dir~-anobenzoquinone (600 mg.) in di- osane ( 5 nil.) was reflused for 18 hr. The solvent was removed in u i c i i o and the residue was suspended in benzene and filtered to reniove the hydroquinone. 7'he filtrate was added to a column of Florisi131 (30 g . ) suspended in petroleum ether and by a linear gradient elution pattern (0-8 dioxane-petroleum ether) with 10-nil. fractions on an autom ic collector there was obtained 28 mg. of starting material. A second linear gradient elution pattern (8-20% dioxane-petroleum ether) gave, by ultraviolet absorption analysis of the fractions, in the following order (in- creasing polarity) I ia-acetoxypregna-4 I 1 l-diene-3,20-dione (XX) 1 7a-acetoxypregna-4,6,1 l-triene-3,20-dione (XXII ) , 1 ia-acetoxy- pregna-I ,4,l l-t,riene-3,20-dione (SXT), and 170-acetoxypregna- 1,4,6,1 l-tetraene-3,20-dione (XXIV) . However, only XXI could he separated and was further purified by partition chroma- tography on Celite,:2 (heptane-methanoli. Crystallization of the material thus obtained from acetone-petroleum ether gave 28 nig., n1.p. 201-206"; [ O ] D $60" ( e 1.157); A,,, 246 mp ( e 15,100); vmnx 3050, 2970, 1745, 16i0, 1630, 1610, 1265, 1250. 890, i19 em.-'.

Anal. Calcd. for C~:$HY&~: C, 74.97: H, 7.66. Found: C, 74 .77: H, 7 . i O .

(32) Celite 8 (Jolins-1\Ienville Company), a diatomaceous silica product.

B.--.4 solution of 17a-acetosypregna-4,1 l-diene-3,20-dione (XX, 101 mg.) and 2,3-dichloro-5,B-dicyanobenzoquinone (72 mg.) in dioxane (5.0 ml.) was refluxed for 18 hr. The hydroqui- none which separat,ed on cooling was removed bj- filtration, and the filtrate was evaporated. Chromatography of the residue on Florisi131 (10 g.) with 7 7 , acet'one-petroleum ether gave the A1j4-3-one (XXI , 36 mg.). Repeated crystallization raised the m.p. to 201-202". The product was identified with material obtained in procedure A .

17a-Acetoxypregna-4,6,ll-triene-3,2O-dione (XXI1).-.4 stream of dry hydrogen chloride vas passed into a solution of 17a-acetoxypregna-4,Il-diene-3,20-dione (XX, 150 mg.) and 2,3-dichloro-5,6-dicyanobenzoquinone (1 01 mg.) in dioxane (7.5 ml.) for 1 min. After 0.5 hr. at rooin temperature, crystals of hydroquinone separated and these were removed by filtration. The filtrat,e was dilut,ed irit,h methylene chloride, and the estract was washed with exces sodium bicarbonate solution, dried, and evaporated to give a yellow residue of XSII (105 nig.), m.p. 190- 192". Since it was impossible to remove t,he color by repeated crystallization, purification of the sample was accomplished by chromatography on Flor i~ i l .3~ Elution with 5yo acetone- petroleum ether gave a material which on crystallizat,ion from et,her gave colorless needles, m.p. 20.5-207°; [ a ] ~ +17" ( e 0.500); A,,,, 285 nip ( e 23,500); vnlnH 3050, 2960, 1742, 1713, 1665, 1615, 1385, 1258. 1242, 1230, 718 mi.-'.

dnal . Calcd. for C2pH?sOi: C, 74.97; H, 7.66. Found: C, 74.83; H, 7.88. 17a-Acetoxypregna-l,4,6,ll-tetraene-3,2O-dione (XXIV).-Into

a solution of 17a-acetosypregn-4,l l-diene-3,20-dione (XX, 300 mg.) and 2,3-dichloro-5,ti-dicyanohen~ocluinone (202 nip.) in di- oxane (10 ml.) was passed a stream of dry hydrogen chloride for about 1 min. After 75 niin. at room temperature the misture was evaporated in w " o (bath temperature 30"), and benzene \vas added and evaporated in ~ ' n c i i o 3 times to remove residual hydro- gen chloride. Methj-lene chloride n-as added, and hydroquinone was removed by filtration. The filtrate \vas evaporated, the residue was again dissolved in dioxane (7.0 nil.)> and 2,:3- dichloro-5,6-dicyanobenzoquinone (202 mg. ) was added. The solut,ion was refluxed for 18 hr. and the hydroquinone was re- moved by filtration and the filtrate n-as evaporated t,o yield :t gum. This n-as dissolved in benzene and added to a column o f Florisi131 (15 g.). Elution wit,h 6 5 aeetone-petroleum ether gave ult,r:tviolet absorbing material. Cuts (50 nil.) were taken and analyzed by thin layer chromatography, which revealed essentially one spot. They \yere therefore combined and evaporat,ed to give a glass (177 nig.). Cryst,allization from ace- tone-pet,roleum ether gave XXIJ- (130 mg.), m.p. l i5-177'; crystallization from ether did not alter t,he melting point,: [ a ] ~ +26" ( c 0.704); A,,, 225 nip ( e 15,900), 252 m p ( e 14,900), 300 mp ( E 13,600): vmax 3000, 2940, 1730, 1660, 1630, lGOT, .

for C ~ ~ H Y ~ O , : C, 7 5 . 3 8 : H, 7.15. Found: C, 75.20: H, 7.52.

17a-Hydroxypregna-4,6,ll-triene-3,20-dione (XXIII).-Drj. hydrogen chloride n-as bubbled for approximately 1 min. int,o :L solution of 17a-hydrosypregna-4,l l-diene-3,2O-dione (XIV, 133 mg.) and 2,3-dichloro-5,6-dicy~~noben~oquinone [lo1 mg.) in di- oxane (7.5 nil.). The flask was stoppered and after 30 min. the solid which had separated was removed by filtrat,ion. The fil- trate was diluted x i th methylene chloride and the estract wts washed with a sodium bicarbonate solution and water, dried, and evaporated to give XXIII (120 nig.), m.p. 200-205". .hi analytical sample (59 mg.), m.p. 212-218' dec., was obtained from a F l ~ r i s i l ~ ~ column by elution with 8% acetone-petroleum et,her. Cryst,allization from ether raised t.he melting point to 222-22.1" dec., [ a ] ~ +55' ( c 0.491); A,,, 286 nip ( E 20,900): vmRX 3410, 3050, 2960, 1708, 1645, 1610, 1580, 13.50, 1225, 1185, 720 em.-'.

Anal. Calcd. for C21H2603: C, 7 7 . 2 7 ; H, 8.03. Found: C, 76.64, 77.27; H, 8.22. 8

, 1260, 1245, 718 cni.-'.