era1 times with ether. The wmiJined extract.; were dried (Na2S04)and filtered. The solvent was removed from the filtrate. leaving an oily residue which was treated with ethereal HC1. l h e solid which separated was taken up in pentane- anhytirous etha no1 ( 2 : l ) and upon coaling. 0.90 p 172%) of product 187 189"; nmr (CDCls) 6 2.7:? [s. 6 H, N ( C H 3 ) 2 j , 2 . ened m, 8 H, aliphatic H I . 3.67 and 3.90 (2 L , F; H 8.17 (m. 4 H, .4rH). 8.20-8.17 lm. 1 H A ~ F I I A V C I / (CzoH26ClS02) C. H, N. d / - l -Vinyl-3,4-dimethoxJ.-1O-dimethylamino-9,1O-dihydrophenanthrene Hydrochloride ( I l a ) . Compound 3 i l .:U p. @.@0:32 mol) was refluxed for 6 hr in a solution of 0.955 :: (C1.024 g-atnml of I( in freshly distilled triethylcarhinol (Eartman. white label:. The cooled mixture was treated with excess 10% HC'I anc tracted with ether. 'I'be aqueou.; lavt-r W A S treatcd NaHCO:{ and the resulting niixiiire exiractiv . with t,ther. The pooled extracts were dried iT;izSO and the ether was reiriovrri Erorn the tiltratc; rintic.: sure. The residual oil was c.hromatographrd on sili( cd with ether. Evaporation of the eluate af'fordeti ;in oily rr-idiic. whirh was treated Lvith ethereal HCI t n give ~ ~ , - l l J i > : i % i i i t solid: m p 182.181"; nmr (CDC 2.02 j b ii II. sI('F1:$lzJ, .i.6 and :1.88 1 2 >, 6 I J , O C H ~ I ,5.1: .-I 1111. : : 1-1. \ l I l > l HI. 7 ~IO--S,O ( m . 5 H. ArI-1 vinyl H i . R , : I ~ I::: : ti ?,rHi, inoi
tK)-I,'-Dihydroxyaporphine
Hydrobromide \Oi)-ti]. !'hi
prnduct. n;p liiO---l8:3", A n d IC,,
t'rom ethanol tci iCji;He&rKOei ('. i l . X
+
( C ~ ~ H ~ ~ CC',I N tl.OK~. I (Ki-1,2-l)imethoxyaporphine (Kuciferine, 9 ) . Thih \vas isola; ed from Nelumbo h t (yellow ~ ~ water lil). co1lrc.tc.d froni w lily pond in the Amana Colanies in eastern Iowa. hy Rn isolation prcrcetiure reported by Kupchan. e t ni:'" nmr ;("DCI,~I ii 2.z.i I s . :\ K. NCHs), 3.67 and 3.86 (s, 6 H. O C l l ~ ) 6.6:; . I S , ! H , irI-1). 7 17 7.37 ( m . :I El, ArH). 8.2F8.50 ( m . 111, X r H ) . ( K )- 1 -Vinyl-3, 4-dimethoxy- IO-dimethylamino-9, IO-dihydrophenanthrene Hydrochloride (Ila). i R - 5 . prepired ( r o i n ( 1 0 - 9 as described for ( * ) - 5 . was treated as described lor d!-i l a : \ ~ 3 1 % -97.70" ( c 0,174, ethanoli. ti/-l,2-I)ihydroxyaporphine Hydrobromide ( d j - 6 ) . ~'oinpoi.nid dl-9 (1.0 g. 0.003 mol) was heated i i ~ 1 !O 125" undcr S::w i i h lG m l of 48% HHr fnr .I hr. After removd of volatile.;. the i o l i t i re>i. due was recrystallized from ethand i o yield 0.60 p 157%1 n t p r n d uct, m p 226-2228" ( Neumeyer, ct i l l , * chaiacteri~cdi hi. ha-e ;I,its HIsaltI.Ancii ( ( ' l ~ H : x H r N Oi'. ~ IH. Y
Antagonism of Slow Reacting Substance in Anaphylaxis (SRS-A)and Other Spasmogens on the Guinea Pig Tracheal Chain by Hydratropic Acids and Their Effects on Anaphylaxis Margaret E. Greig* and Kobert 1, lo00 mg/kg, respectively. The longer chain acetal 3 was active orally and subcutaneously but a t higher dose levels. Thioacetals 4 and 5 did not exhibit any antifertility activity a t the doses tested. Epididymal cysts and antispermatogenic effects were observed in a few of the rats which received the higher doses of compounds 1 and 2. This has been previously reported234.7 and appears to occur only in rats. No epididymal cysts or abnormal effects on the testes were observed in males receiving compounds 3, 4, and 5 . The sex accessory organs were normal in all animals which is consistent with other reports237 t h a t compounds in this series do not cause androgenic or antiandrogenic effects. Our findings substantiate the previously reported male antifertility activity of compound 1 and 2-substituted-4(chloromethyl)-1,3-dioxolanes. We have also found that dithiolane 4 and dithiane 5 are devoid of biological activity at doses comparable to their oxygen analogs.
Experimental Section Melting points were determined on a Thomas-Hoover Uni-Melt apparatus and are uncorrected. Analytical results are within *0.4% of the calculated values. Ir spectra were recorded on a Beckman IR-8 as neat samples and nmr spectra were determined on a Varian .4-60 spectrometer using CDC13 as solvent with triniethylsilane as internal standard. The ir and nmr data of all compounds were consistent with the proposed structures. 2-Heptadecyl-4-chloromethyl-1,3-dioxolane ( 3 ) . A solution of 5.5 g (0.05 mol) of l-chloro-2,3-propanediol, 13.9 g (0.05 mol) of octadecyl aldehyde (prepared from the bisulfite),g and 100 ml of benzene was refluxed in a Dean Stark apparatus for 15 min. Then 200 mg of p-TsOH was added and the solution azeotroped for an additional 4 hr. The solution was washed with 10% aqueous YaZCO3 and HzO, dried (MgS04), and concentrated. Column chromatography of the residue on Silic AR, CC-7, eluting with ethyl acetate-hexane (1:3) and distillation of the crude product gave 3 19.8 e. 54%): b D 144-150" (0.001 m m ) . .4na/ iC21H41C102)C, H , C1. 2-Hexvl-4-chloromethyl-1,3-dioxolane(2). This compound was prepared in the same manner as 3 and afforded 2: bp 82' (0.4 mm) [lit.1o123" (14 mm)]. 2-Hexyl-4-chloromethyl-1,3-dithiolane(4). To an azeotropically distilled mixture of 14.4 g (0.1 mol) of heptanal, 100 ml of benzene, and a catalytic amount of p-TsOH was added 14.5 ml (0.1 mol) of l-chloro-2,3-dimercaptopropane.11 When the theoretical amount of water was collected the solution was washed with saturated aqueous KzC03 and HzO, dried (KzCOs), and concentrated. The residue was purified by a n initial distillation (bp 118-121", 0.1 mm), followed by column chromatography through Silic AR, CC-7, using ethyl acetate-hexane (5:95) as the eluent and a final distillation through a short-path distillation apparatus to afford 4: 3.0 g (12%).Anal. (CloH19C1S2) C, H, C1, S.
