Journal o j Medicinal Chemistry, 1970, Vol. IS, ~ V O6. 1247
N E WCOMPOUNDS
tested for uterotrophic4 and antiuter~trophic~activities in the mouse. It was dissolved in olive oil and injected subcutaneously. It displayed no significant activities in 3 daily doses of as much as 300 gg. I n vitro the thiophenol I1 showed no competitive binding affinity4 for estrogen "receptor" sites of the mouse uterus in concentrations 103 times the effective concentrations of I.
oxideI4and hempa (hexamethylphosphoric triamide).4sb We therefore prepared a number of derivatives of citronellol (3,7-dimethyl-6-octenol) and citronellylamine (3,7-dimethyl-6-octenylamine), several of which bear a structural resemblance to these sterilants, for testing as potential sterilants and juvenilizers. The test compounds are listed in Table I. TABLE I Yield,
Experimental Section
meso-3,4-Hexanebis(phenyl-4-disulfonyl chloride).-To a solution of 3 g (0.013 mole) of meso-3,4-diphenylhexanes in 20 ml of dry CCl4 in B dry atmosphere was added 6 g (0.05 mole) of C1S03H and the mixture was stirred for 12 hr a t room temperature. The suspension was filtered. The product (8.5 g) was crystallized from CHC13 after which it melted at 220-226". Anal. ( C ~ ~ H B O C ~ C, ~ SH S IOS.6 ~), meso-3,4-Hexanebis(phenyl-4-thiol j (II).-The crude disulfonyl chloride was reduced according to a literature procedure.' SnC12.2H20 (10 gj and 50 ml of HAC was saturated with anhydrous HCl. The solution was maintained at 80°, 6.5 g (0.015 mole) of the sulfonyl chloride was added and the solution was stirred for 1 hr. The solution was cooled, poured into 30 ml of concentrated HCl, and filtered. The filt,rate was extracted (EtzO), dried, and crystallized several times from CaHs. The product was sublimed at 170" (0.01 mm); yield 1 g (25%), mp 147-1.50°.3 Anal. (C18H&j C, H, S.8 Absorption bands (or peaks) of spectra (nmr, ir) were as expected.
Acknowledgments.-Smr spect'ra were kindly recorded by Dr. s. 0. Almquist, a t the Department of Chemistry, College of Sgricult'ure, Uppsala. This work \vas supported by the Swedish Cancer Society. (4) L. Terenius, M o l . Pharmacol., 4, 301 (1968). ( 5 ) S. Wawzonek, J . Amer. Chem. Soc., 68, 1157 (1946). (6) C : calcd. 49.7; found, 49.1: 8 : calcd, 14.8; found, 15.6. (7) C . S. Marvel1 a n d P. D. Caesar, J . Amer. Chem. Soc., 73, 1097 (1951). (8) T h e analyses were within +0.4% of theoretical values. Melting points a r e uncorrected.
Compounds Related to Insect Juvenile Hormone. V. Derivatives of Citronellol and Citronellylamine
R
%
Bp,OC(mm)
Formula
-4. Cozpounds Derived from Citronellol (3, i-Dimethylethyl-6-octen-1-01)
R0--P(Oj[NCHJJi -€YO) -C(O)N
o 1I -CNI
(rig) (CH,),
128-133(0.15)
63
Ci4H3iN202P
142-180(0.10)
53
CiaHliN20J'
83-89(0.05)
90
Ci3H2jNOz
84-93(0.05)
86
CuHiaNO?
B. Compounds Derived from Citronellylamine (3,7-Dimethyl-6-octenylamine)
U
N
H
R
-COzC2Hj 102-103(0.1O) CONH(CHL)~NHC(O) 138-13g8 --P(O)[N(CHJ.I, 165-150(0.
87 97 27'
C13H2&S01 CisH&ah'aOi CI4H32NaOP
163-180(0.10)*
24'
CI4HZsN30PC
-€YO)
(q
C. Miscellaneous R'C02C2HSd 107-111(0.12) 7 2 Ci3Hz&02 R"C02C2HOe 123-130°(0.03) 84' C13HniNOa a Nelting point following recrystn from EtOH. * Decomposes on distn. c Combustion analyses were poor, but the nmr spectrum (see Experimental Section) was entirely consistent. Commercial citral was converted into its oxime and reduced with LAH to a mixture of cis and trans amines. R' therefore is (3,idimethyl-2,6-octadienyl)amino. e K" is (6,7-epoxy-3, i-dimethylocty1)amino. f Yield of the epoxidation step.
Only P,P-bis( 1-aziridiny1)-N- (3,7- dimethyl-6-0~teny1)phosphinic amide showed chemosterilant activity PHILIPE . SOKXET, MEYERSCHWARZ, AND N. WAKABAYASHI against house flies, Xusca domestica L. The carbaEntomology Research Division, Lr. S. Department of Agriculture, mates and their epoxides mere the only compounds to Beltsville, Maryland 20706 show juvenile hormone activity against Tenebrio molitor L.637 Received January 26, 1970
A number of investigators have reported that certain compounds having insect juvenile hormone activity are also inhibitors of embryonic development in some species of insects. Also, the "dihydrochloride" of methyl farnesate has been found to be a very effective sterilant for female Pyrrhocoyis a p t e m s (L.).2 I n addition. llasner and coworkers described the phenomenon of sexually spread insect sterility that occurred when they used compounds with known juvenile hormone activity. Among the compounds best known for their chemosterilant activity are tepa [tris(l-aziridiny1)phosphine (1) I(.Slilma. a n d C. M. Williams. Kature (London). 210, 329 (1966); L. dead. Sci. C. S. 67, 595 (1967). (2) P. Masner, K. S l h a , a n d V. Landa, J. Embrgol. E z p . M o r p k o l . , 20, 2 5 (1968). 13) P. Masner, K. SISma, a n d V. Landa, .\'nture ( L o n d o n ) ,219, 395(1968).
M , Riddiford, a n d C. AI. Williams, PTOC..Vat.
Experimental Section The chem anal. were performed by Galbraith Associates, Inc., Knoxville, Tenn. Kmr spectra were obtained with a Varian Model T-60 instrument, and ir spectra were recorded as films or mulls with a Perkin-Elmer 137 ir spectrophotometer. Where analyses are indicated only by symbols of the elements, analytical results obtained for those elements were within ~ k 0 . 4 7of~ the theoretical values (see Table I ) . Citronellol Derivatives.-Citronellol was converted into its chloroformate by treatment with 1 equiv each of COCL and E t r S . An ethereal soln of COCL >%-as added dropwise to a wellstirred s o h of the alcohol and amine in Et20 while the mixture was held at 20-30". The mixture was allowed to stand at room temp for 1.5 hr and filtered by suction (Et20 rinse). The filtrate (4) G. C . LaBrecque, J . Econ. Entotnol.. S4, 684 (1961). (5) S. C. Chang, P. H. T e r r y , a n d A . B. Borkovec, Scwnce. 144, 57 (1964). (6) W.S.Bowers, a n d M. J. Thompson, rbzd.. 142, 1469 (1963). (7) Mention of a pesticide or a proprietary product i n this paper does not constitute a recommendation or endorsement of this product hq t h e U. S. Department of Agriculture.
wa.. washed with ILO, dried ( M ~ S O Cand ) , coiiod. The yield of crude product was 8976 (C=O, 1780 cm-l). The chloroformate was converted into the desired carbamate by adding I equiv each of a11 amine (ethyleriimine or Mez") arid Et&-. The roriditionn arid work-up procedure paralleled those just described. Cit,roiiellol was converted into the P derivatives by treatmelit with 1 equiv each of the required acid halide and E:trS. Citronellylamine Derivatives.-The amiiie \vas prepared b y LAH reduction of the oxime.* However, yields were variable :ind depended largely o i i the freshiiess of the reducing agelit. Citri)iiellylamirie reacted with hexnmethylerie diisocyaiiate iti Et20 exothermically t o produce the diurea as ii pp( . The amine w:ts converted into its other listed derivatives hy reaction with the :wid halide :tiid Et3N as described for citronellol. Epoxidatioii of the et,hyl (3,7-dimethyl-6-octeiiyl)c~arbamate w:ts (wried out with 1 eqiiiv of ~n-chloroperbeneoi(' acid in CII2CI2. The niixtrire was held at 5-10" driritig addii of the olefirts and was allowed to statid at, room t,emp overnight. After the orgaiiic: solti w:t* dried INazSO,), extr:wtiort with NRzCO:,, conid, arid dist by iisitig a short-path dihtii apparatus;. The nnir spectrrini of P,P-bis(l-:rxiridiiigI)-.~-(~,7-dirneth~~lti-oc~teiiyl)pho~phii~ic~ :imide showed the followiiig :tbsorptions: 0.XX d (CH3C1I),1 .,57 :tiid 1.65 (cis n i i t l I i,:itts allylic. M e , respec-
T \J3lri 1
Acknowledgment.--The aut hors express their grat itudc t o C'. G . 1,nRrecque a i d co\vorl;ers, Eritmomolog\Itesearch Division's Insects .lffecting 1Iaii Iiivestigatioiis I,ahoratory, Gainesville, FIL, for t h e tests of houseflj. stcrilit~.. (81 I). .\riguni
a11d
0..leger, f l e l r . Cliini. . I r f , c . . 3 1 , 881 (195.1)
Synthesis of Nes+ Urethans. p-Ethylsulfonyland p-~imethylsulfanioylcarbanilicAcid Esters
Scvclrul p-ur? buliotiS.lcarbnnilic acid e,tcr:, i v t w rcported to have arititumor activitie.. I S e w urethaii, lihted in Tablc I were prepared b\ Curtiub degradation of appropriate benzoyl azidet
