TABLE TI1 EVIWCI~ U Y ll.\Lii)E Iuiis O N AChE IIYUILULYSIY O F AGh
\? NI,riioGm O F L4NIIjINES THE in i%,O AC'I'IVITIES O F THE
TABLE
~ L E C ' T l L O N I CCtIAILlCTEIL O F 'THE hhU
BENZIMIDES ItELATIVE TO CO~~RESPOKDING SULFONIMIDES
amoles of ACh E pli t l h r
Sub-
alituerit
4-NIT, 4-CTIzO 4-CHa I3 4-Cl 4-NO2
Lug (IjC,)'',*
4.33 4.47 4.57 4.80 4.80 5 .83
rl.v
cs
Anilines 0.388 0.433 0.433 0.477 0.4.59 0.484
0.077 0.081 0.081 0.083 0.082 0.106
q.\2
0.006 0.007 0.007 0.007 0.007 0.011
Beiizamides
3-CIIa, 4-CII80 4-CHaO 8,4-CII, 4-CI-1, 8-CHs I1 4-C1 4-CN
0.148 0.022 0.041 0.148 0.0'22 40" 0.03.; 0.148 0.022 5.40 0.042 3.40 0.148 0.022 0.036 0.149 0.022 0.018 5.40 5.25 0.149 0.022 0.000 0.148 0.022 j.10C 0.027 0.151 0.023 4.0 h (sinister) This a i accomplished reactioii of CHCH CH, metaramiriol I\ ith execst SOCl t o give t h c h~ c h i ) I chloride of 8 follonetl by catal? tic reduction t o 9. \ NHCOCH, Biological Results.--Bo t h of the opt ictil I? : i r ( I vv tAi eo-4 depleted m o u v heart riorepiiiephrint~ t o :tp6 proximatel! the same extent, h:iving El>,"'\ of :ibout confirming that these compounds pobsess the predicted 30 1~1g,'kg.~~ Thib i i in sharp contra-t t o thcl ( ~ yi t i o o thveo configuration.6 S o trace of the erythro product series in i\hich metaraminol, ED,( of -0.1 mg kg, 1could be detected by nmr. much more active than its eiiaiitiomer.li We have used the difference in rimr chemical shift In the (log, the thi eo i-onier? exhibitd h~ n i p t 110of the benzyl hydrogens (HI) in the eigthvo and threo mimetic activit) after int raveiioub ndniini-tratic J I i isomers to study the isomerization of metaraminol iii The lS',2S iwmcr of 4 had mtirhed prehwi.. iIiotropw. 6 N HCI. After several days at looo, the erythro ant1 chroriotropic iictiori* heiiig :ibout 0.1 tinic's :Iisomer n as converted cleanly into a mixture of the t u o a c t j w in this respect i i h metaramiriol. Tlie 1H.2K isomers containing 55 f 5% of the threo i ~ o n i e r . ~ ihonier n a b considerabl> le ictive than it- eii;rntioint~r However on a preparative scale, the threo isomer could It appear< that noiqinephrine depletion :i.: meiisuiwl riot be isolated in a pure state from the equilibration in thiq T\ orl; i i a functioii of the combined stereomixt urc. rheinistrj- :it the amino- and h! clroxyl-bearing c:arbo~i The (-)-acyloin 5 has been sho\vn by Tristram, atom< and i- not wlel) rc.lated to the -tereochcmistr\ a t et to have the R (rectus) corf~guration.~Sirice m y oiie c e t i f e r . metaraminol has the eryfhi o Configuration arid has been prepared from 5 by a method not involving inversion at Experimental Sectionl the hydroxyl-bearing carbon atom,I0 the absolute configuration of metaraminol must be I R , ' I ' A S . ~ >In ~ ~adcli~~ m-Benzyloxypropiophenone, l)p 153--168" (0.1 n i i i i j . 2 k ' \!:I.. prepared in 95.5$ yield from ~ ~ z - h ~ d r o s ~ p ~ o ~ i i ~t I~t < ~, 1 ~ 1 ~ 1 ~ 1 ~ 1 tion, van Roshumlj has quoted a persoiial communicamethod of Suter arid tion from Dirkx that optical rotary dispersion qtudie.: r,i-Benzyloxy-a-bromopropiophenone(1I.---. .1 solution of have e-tablished the absolute coiifiguratiori of metag (0.203 mole) of BrDin 50 ml of CH& was n t l d ~ ovc'r i 0.75 h r raminol as l R , W . to n stirred d u t i o n of 50 g (0.208 mole) of nl-bc.ilz?.lo~!-))rolJiophenoiic~in 500 nil of CH . N? \\-as buhk)lrd throiigh t h r WOH
I
(ti) . J H , , H ~ = 4.2 H z for tlie fumarate salt of metaraminol (erythro-4). .imino alcohols v i t h t h e ephedrine (ergthro) configuration have been reported to have J H , . H ? = 2.5-4.3 Hz while those having t h e pseudoephedrine (threo) configuration h a r e J H ~ , H = ? 8-9.6 Hs: P. S. Portoghese, J . M e d . Chem., 10, 1057 ( 1 9 6 i ) : R. H . Uloth, J. Kirk, W. Gould, and A . A. Larsen, & i d . , 9 , 88 (1966); G. G. Lyle a n d L. K . Keeler, J . O w . Chem., 91, 3921 (1966); .J. D. Hyne. Can. J . Chem., 39, 2563 (1961). (7) These results are similar t o those obtained b y H . Emde [ H e l r . Chim. .4clu, la, 377 (1929)l from rotation measurements for t h e isomerization
