pheiiyl t ried iii the 3-oxy series had been dclet erious. I17horeas the %oxy series had requirrd 2- or I-substit 11t i o i i oii t he pyrrolidine ring, t he libcia-oxy series s u f f ~ r > slight t o (Lompletc loss of activity 0 1 1 ring suhstitutior1 additiotial to 1,X-, i n the order 3-, 2 - , 1-. 'Thew ar(s i i i t cresting idatioiiships i r i i lit. iiida-oxygeti seriw bctn-cvti heaviness of t'-all;ylatioii, gradatioii i i i zn-it tcisionic. rharacter. aiid loss of activity. i i i d a I-:thcrifirat i o i i scoiiiiiigly iiiuzzles c.oiisidcrably t 1irs:ct iiitcraczt ioiis of 2-alkylat ion. I,'iiiaIly, efforts of alteratioiis i l l S-subst itlit ioii ar(8 i i i w l i sliai-pcr i t i thr mefa-oxygeii scrics ihaii it1 the
Acknowledgment. - 'I'he authors thank L h . li. L. 13om-nian aiid 111..IT. 11. Crooks, ,Jr., for helpful ad\-iccl and consultatioii. 1 1 1 , . 1:. €1. Olivcr for the iiiicro.\I. Tanner for the physical measureI.: Richards for help ill the rctsolutioii of the parent coinpouiid, aiid lliss 1,. Scotti. Miss .I Was, and ALrs. S . Stsiiat for important participation i i i the pharniacologic~aln-ork.
Bicyclic Homologs of Piperazine. Y1l.l Synthesis aiid Analgesic Activity of 3-Aralkenyl-8-propionyl-3,8-diazabicyclo[3.2.l]octanes
\Vjih the aim of eiihaiiciiig the aiialgesic iwtivity of 3-ciii1~a~myl-8-propioli~~l-~~,~-ifi:izabic~cloj3.2.1]oct~atie (l), 25 derivatives were qxthesized ill which t,lie 8-aralkeiiyl group was vnrioii>ly modified. Some of these comp(Jl1~ldSexhibited ail analgesic pot,eiic)- romparable with that of 1. 111the preccedirig paper of this sericls.' t h e synthesis of stitutioiis oil the aroiiiatic ring (2-12) and on the ethylanalgesic3 :,(,*lll,j,
('ry, l ~ f ~ l l l Yielll,
';
60-62 l.;t,her-pctr. er her (X O-C:IC&,L Ether-petr. ethor lii U L - C I C ~ H ~ ~ ' 40-43 63-65 Ether-petx. ether IiF p-ClC6Hi O-OzNC6H4e 126-128 Eth:tnol 64 Etlianol 07 V L - O ~ N C ~ H + * 117-1 19 p-02NC6H4' 140-143 Ethiliiol S0 ;Lj p-HICCe.HdU 85-90 ( 0 5 j o-H:ICOC~H+~ 12s-130 ( 0 6 ) ... 40
