SOTES mmol) in H?O 110 ml). -4cidification gave thiol 7, which showed no change by ir or tlc. Mercury (II)Bis(2-carboxy-l-cyclohexylMercaptide) (14).-Thiol 7 (20 mg, 0.12 mmol) in 2 ml of EtOH was treat,ed with an ewe.:. of 1 0 5 Hg(CX)l solution in EtOH. The mercaptide 14 precipitated oil cooling, and recrystallization from EtOH-H2O gave colorles:. plates (13.6 mg, 4 2 5 ) : mp 160-161": ir (KBr) ;5:300-2400, 1690, 1440, 1400, 1240, and 1200 em-'. tlc on Brinkmaiiii A I S Polygram (polyamide) developed in MeOH at ca. 25" hhowed only a >ingle spot under uv light ( R E 0.24). dnal. CitH?,HgO$,) C, H, S.
2-~2'-Protoaminoethyldithio)-l-cyclohexanecarboxylate(8).Thiol 7 1.02 g. 6.4 mmol) in 6 ml of EtOH was added during 10 mi11 tu a stirred solution of 4 (1.61 g, 6.4 mmol) in 4 ml of 1:; Et0H-H2O. After 4 hr at ca. 25", a cold solution of KOH (0.71 F;. 12.7 nimol) in 3 ml of HnO was added, and the mixture %-as >tirred at 0' for 0.3 hr. In order to initiate precipitation, Et20 ( 1 mli was added. After 2 hr a t 0" a white solid separated. Di-ulfide 8 was collected and washed with H2O and with EtOH. A white powder resulted (0.86 g, 5 7 C c ) ; mp 21'7-219" dec. Retallizatiori from H?O (100') gave 8 as colorless plates with nip 230" der. Tlc of 8 on Eastman Chromagram Type K301R i-ilica gel) developed with EtOH-H?O-XH40H (25:3:4)11 a t ca. 25' showed only a single spot (Ri 0.53); ir (KBr) 32002200, 1610, l.il0, 1400, and 1275 em-'. dnal. (C,HI;SOUS?) c,H. N , 8. 1rn ns-2-Aminoethyl 2-Chlorocyclohexyl Disulfide. HCI (lo).The thiol 9 (1.51 g, 10 mmol) and 4 (2.57 g, 10 mmol) were htirred ill 20 ml of 2:l EtOH-HrO for 0.5 hr at ca. 25'. Evaporation belon 30" gave a white residlie, which was dissolved in 25 ml of H,O and was extracted with 50 ml of Et,O to remove unchanged 9. The aqueow layer then %-asshaken with 50 ml of Et20 while 10 ml of an iced aqueous solution of KOH (1.7 g, 30 mmol) was added. The HZO layer was extracted twice more with EtyO. Each organic layer was backwashed with H?O and immediately dhakeii with the same portion of 1.0 ml of 12 AYHC1 i n 10 ml of H,O cooled in an ice bath. The HC1 solution then was treated with 3 ml more of 12 .Lr HC1. Precipitation of 10 occurred immediately. The crude 10 was isolated by filtration, washed with hesaiie (20 nil\, and carefully dried in a desiccator (CaCl?). Di:.iilfide 10 was washed with 31enC0 and dried under reduced preasurc; 0..53 g C200r,), mp 148-150". Tlc of 10 (in Eastman Chromagram (Type K301R) developed with 9 5 5 EtOH at ca. 25" showed only a single spot ( R f0.42); ir IKBr) 3200-2300. 1375. 1500, 1440, and 725 em-'. Anal. (C,H,;CIiNS> I C, H, C1,S. a-t2-Protoaminoethyldithio)cinnamate (12).-Thiol 11 (23.00 e. 0.13 mol) in 200 ml of EtOH was added with stirring to 4 TJ3.00 g, 0.13 mol) in 120 ml of 1:1 EtOH-HUO. The mixture was stirred for 4 hr at, ea. 25'. Evaporation below 30" gave a paste. which was dissolved in 100 ml of H20. A cold solution of KOH (14.1 g, 0.23 mol) in 100 ml of H 2 0 was added s l o ~ l y . .I red oil neparated. The mixed oil and HI0 were washed with 100 nil of EtrO. The aqueous layer was decanted from the oil, which then solidified. Recrystallization from H2O (100') gave 12 a,: a red-orange powder having rnp 135-138" dec; 9.27 g ( 2 8 % ) : ir iKBr) 3100-2200, 1600, 1540, 1450, 1340, 850, 780, 7.50, and 680 em-'. An identical sample (by ir) was recrystallized repeatedly from H,O to give 12 having constant, mp 136138' dec. .-lnal. (CllH13XO&) C, H, S , S.
dineacety1)-a,w-diamine derivative3 were effective as chemosterilants for houseflies' and some acted as sterilants for male mice.* These amides seemed to be less toxic than the corresponding urea derivatives3 and we were anxious to replace the aziridine alkylating function with another one, nameiy, the methanesulfonate group. A series of these derivatives was synt hesized from the corresponding hydroxyacetyl derivatives and evaluated for its effects on the reproduction of houseflies and mice. Tables I and I1 summarize the chemical data on the carbomethoxyacetyl and hydroxyacetyl intermediate. and Table I11 summarizes the data on the final methanesulfonates. TABLEI BE( C . ~ R B O ~ ~ E T H O X Y . I C E T ~ L ) D I . I Y I N E S ,
CH30COCH2COSH(CH2),SHCOCH2OCOCHa Yield,
W. A . RKISN~.R
XSD
J. G. JOH.IXSSOS
Life Sciences Research, Stanford Research Institute. Menlo Park, California
n
5%
MP, o c
6
37
187.5-188.5 169-160 147.5-148.5 116-118 117.5-119 95.5-97 122.5-124.5 214-216.5 142.5-143.5
44 47
8 9 10 11
12 p-CHzCsHaCH? m-CH?C6HaCH!
47 49 60 37 36
Recrystn solvent H.0
Formulaa
Dioxane f H20 Dioxane f H r O E t O H + H20
ClaH?&x206 CILHZ~KZOE C16H2a~?Oe Ci;Hms?06 CiiH3zNzO~
E t O H + H20
CisH~nN?0e~
Dioxane H20 Dioxane HzO RleOH - Et20
C:oHseSz06 C~HzoK206' C~H?o?j?08
H9O
+ +
All compounds were analyzed for C. H, N. 59.0; found, 58.5. c C : calcd, 5 7 . 2 : found, 57.7. a
C:
calcd,
T.IBLEI1 BIS(HYDROXY.~CETTL IDIAYIK ES, HOCH,COXH( CHz),SHCOCH2OH 11
Yield, %
3Ip. ' C "
Formulad
6 25 126- 129 CioH2oXz01 7 78 11.5-116 CliH22T204 8 75 116-117..5 CI&~N?O~ 9 82 126- 127 Ci3H2aNzO4 10 83 122.5-123.5 CiaH28N20, 11 93 122-123 CljH30~204 12 74 129.3-1 31 C16H32N204 p-CH?CeHaCHz 9.i 223-227c CIZHI~NZO~ a All recrystallizations were from H2O except for those noted. b liecrystallized from EtOH-H20. Recrystallized from dioxaiie-HUO. d See Table I, footnote (1.
T ~ B LI11 E
BIS(METH.WESULFOXYLOXY.~CETYL)DI.IMINES, HaCSO2OCH&ONH( CHz)nSHCOCH200zSCH3 n Yield, 7 Mp, o c a Formulab 1 7 31 103.5-106 C I ~ H ~ ~ N L O ~ S ~ 2 8 39 127-129 CiiHt8N208Sz 3 9 33 109-113 Cl.jH3oNzOsS2 4 10 33 120-124 C16H3*N208S? 5 11 57 11.5-1 18 C17H34N208S? 6 12 75 127-130 C18Ha6~20& Recrystallized from 31e2CO-Etn0. b See Table I, footnote a.
Compd
(14) D. Braun and H. Geenen. J. Chromntog.. 7, 56 (1962).
Effect of Organic Compounds on Reproductive Processes. VIII. Methanesulfonyloxyacetpl Derivatives of Diamines
319
a
Experimental Section
S,S'-Bis(carbomethoxyacetyl)-ol,w-alkylenediamines.-ri solution of carbomethoxyacetyl chloride (0 04 mol) in 100 ml of C6H6was added slowly to the diamine (0.02 mol) dissolved in 100 ml of CoHC, and 5 g of anhydrous K X 0 3 was suspended in the same solvent. The reaction mixtuie was stirred at room tem-
Receiced October 20, 1969
For >ome time we have been interested in the effects of various alkylating agents on the reproductive proce-e- of houqeflies and mice. Certain N,N-bis(aziri-
(1) W.A. Skinner, H. C. Tong, T. E. Shellenberger, and G. F.Nemell, J. M e d . Chem., 8 , 647 (1965). (2) W. h.Skinner and H. C. Tong, Ezprrientia, 24, 924 (1968). .iSkinner, . >I. Cory, and J. I. DeGraw, J . .Wed. Ckem., 10, 1186 (3) \I-. (1967).
