Steroids. CCVI1I.l
Ring A Modified Hormone Analogs. Part I\-.
2-Chloro and
2-Halomethyl-A2-androstenes
'I'hc biological sigiiificaiice of sp' hyhridizatioii at C-2 aiicl C-S i n t'he aiidrostaiic molecule \vas clearly demolistrated in Part I?of t,liis series. As a result of t,liis finding our attention was focused 011 tlie preparatioii of C-2 suhstituted A?-aiidrosteiies ill order to eraluatr tlicir biological properties. The present paper is a contiiiiiation of this general study1 and describes the syiitlic-. sis of 2-chloro aiid 2-lialomcthyl derivatives of A?-aiidrosteiie-I ip-ol acet'ate. Ilecciitly Mamlok and ,Jacques4dcscribcd a gciicral procedure for the preparatioii of vinylic chlorides i i i thc aiidrostaiic series. This method involrcd thr treatment of the steroidal ketoiir \\-it11phosphorus pciitachloride i l l boiling chloroform to afford an uiicharactc.rizetl intermediate, formulated by t'lie French workers as a gcm-dichloro compound. Subsequent dehydrolialogeiiatioii with collidiiie led to the vinyl chloridr i i i 40-(;0%, yield. Exteiisioii of this reaction t o the w t c r tlerivatircs of a1idrostanc-l7,3-ol-2-oiic (IIg) appearctl to offer a route to 17-hydroxy-2-chloro-il~-audrostciies. .Utliough %ketosteroids liave received \.cry littk attmtion, a uumbcr of procediires liave hceii rccordcd i n tlic literature for their preparatioii." The metliotl of Slates and Wcntller"" appeared to he tlic most ~ O I I \ T I I icxiit aiid was adopted for this u-ork. Ileactioii of i12-aiidrosteiic-l 7/3-01 beiizoatc (Ih) \\.it11 S-hromoacctamide a i d perchloric acid i n tetrahydrofriraii solution afforded a crystalliiic bromohydriii IIn. which was directly convertcd to .~E-hromoaiidrostaii(,1 7/3-ol-?-olie benzoate (1113) witli chromium trioxide i l l acc.toiic-sriliuric avid soliitioii." Ilchromiiiatioii of tlic krtoiic' IIh with ziiic cliist i i i awtir acid yicldctl andim..tailc-li/3-ol-2-olic hcnzoatc. IIIr) .: I i i the Sam(. maiiiicr, A2-aiidrosteiie-lip-ol awtatc. (IC)' was convcrttd to aiitlrostaiie-1'iU-ol-2-one acetate (IIf), \\-itdiout purificatioii of tlic. intermediate bromo-
H & x Y
Ii 1.'
(ti.
('I,,
III.
C'O(
liydriii IId or tlie bromoketoiir IIP. .ilkaliiie liydrol? 5is of tlic ?-keto arctatc IIf gavc aiidrostaw- 178-01-2one (IIg), ideiitical 111 all rebpwts with thrx product 0 1 ) taiiicd by sapoiiificatioii of' the I7-t)eiizoatc I I r Before p r o c t w h g with tlic Iialogenutioii of tlic 2-h(1toiie IIf witli phosphorus peiitachloridc. a prelimiiiary investigation of this reaction \rah carried out ith dillyclrotestosteronci acac%ate (IIIa). Trcatmellt of tlic
( t i ) Irhy K . K. E n d ? m i l s t r i r i ' t s o f l:Htli S;iti
