ilSi 'r.\IJI,E 1 Y,Y'-~ISC.\ltl~.\MoYL.\ZIKIUI"
CNHCOSHRNHCON~ 1-ield,
---
- --Calcll,
%,
- -
~--
-I'"rlllll.
',I-
Q
C
1-1
N
c
100-1o"g 110-112
55 31
61.0
9.74
18.0
61 .o
+300
22
,ji.l
7 99
22.2
56.8
8.09
21 , , OC''
I1
10.0
Cornpoiiiids polymerize upoii slow heatiiig; nieltiiig poiills were taketi on a preheated Fisher-Johns melting poiiit block. tian, .Inn., 566, 210 (19.50), reported mp 104'. 11
T.\BLEI1 REPRODLXTIOX OF ~IOUSEFLIES"
EFFECTS O F C O M P O C N D S O K
_-_____ Coinl,ound
1
2 J
4 1
6
\ \ t yc in feed
1.0 0.1 0 . 01 1.0 1.0 0.1 1.0 0.1 0.01 1.0 0.1 1. 0 0.1
---1
2
2
0 4 5.5 39
11
63 38
Q egg l~atchb------D a y s of oviposit ion-----3 4 5 6
1 1
2 24 61 56
50
5s
/
I
3
0
0
0 8 58 43
/ / /
/
/
/
/
/
-
70
48
-
90
89 3i 31 38 82
39 68 39 43 40 90
79
94 -70 41
73 84 44 52 62 88
5.5
/
0 10 ,56 .58
20 68
/ 0
7
0 13 50 i3
/ 0
/ / / 78 53 32
GO - 70 i4 SO 95 91 89 T w o hriiidred flies were iised for each experiment. Horizciiital lilies indicate that no data were obtained: slant lilies illdiuate that no eggs were laid by the treated houseflies. i
60 60
'1
dines also were effective chemosterilants. Some of these compounds were effective chemosterilants for houseflies a t 0.1% concentration in the diet while N,S'trans-viriyleriebis-I-aziridiriecarboxamidewas effective a t O.Olyc concentration. We were interested in preparing bis-N,S'-carbamoylaziridines from some of the carrier groups used in the aziridineacetyl series112and evaluating them as housefly chemosterilants. Table I lists the chemical data of those compounds prepared by reaction of aziridine with the appropriate isocyaiiate. Table I1 lists the results of cvaluatiiig tlicse compounds as housefljr chemosterilants. Experimental Section General Method for N,N'-Biscarbamoy1aziridines.-Isocyanates were prepared from the dicarboxylic acids by the procedure of .-illen and Bell.4 The crude isocyanates in a small amount of benzene were added after filtration t o an ice-cold solution of 2 equiv of aziridine in beiizene.' The reaction niixture was stirred for 1 hr a t room temperature and filtered. Recarise the rireas tended to he heat sensitive, the recryatallizai i ~ i i i swere t l o i i r w i t h :L i i i i i i i i i i i i i n of Iiwiiiig. (4)
C.1:. 11. .\lien and A . Bell, Org.
S y n . , 2 4 , 94 (1941).
17.7
b
11. Ben-
1,4-Cyclohexanedipropionic Acid.-To a solution of 0.68 g (29.6 mg-atoms) of Xa and 5.4 g (14.8 mmoles) of trans-1,4diiodomethylcyclohexane,j mp 77-79', was added 7.90 ml (44.4 mmoles) of diethyl malonate. The solution was heated at reflux for 7 hr. Ethanol was evaporated in uumo, and the oily residue was partitiorled between ether and HsO. The ether was dried (IIgSOI) and evaporated in vacuo. The residue was stirred a t reflux with 23 ml of 6 .\- HC1 for 16 hr, evaporated to dryness in z~ucuo, and heated at 190" for 0.5 hr. The residue was then partitioned between 0.1 .Y S a O H and ether, and the basic solution was acidified to p H 1 with 6 .YNaOFI and filtered. Kecrystallization from acetone-HSO yielded l.ig (GOYc) of white crystals, mp 23d-23i" (sealed, evacuated capill dnal. Calcd for C1?H?,O~:C, 63. H, 8.83. Forind: C. 63.07: H, 8.64. 1.4-Cvclohexanediacetic Acid.--trans-l.4-Cvclohesanediacetic , . acid ' x a s prepared according to the procedure of Garcia and Wood,6 mp 226-226" (lit.6 226-227'). p-Phenylenedipropionic Acid.-p-Pheiiylenediacrylic acid (10.0 g, 4!5.9 mmoles), 250 ml of tetrahydrofuran ( T H F ) , aiid 3 scoops of Raney Xi W-2 (4.2 kg/cm2, 60") absorbed half the theoretical HS in 24 hr. After addition of 1.0 g of PtO? iii 5 nil of T H F , hydrogenation (,-ame conditions) went t o conipletic~ii. The catalyst, was filtered, and the solution was evaporated t c J dryness in z'ucuo. The residue was recrystallized from 100 ml of T H F to yield 6.8 g (675;) of white crystals, mp 228-230" ).
Biological. 1lethods.-All the aziridine derivatives listed i r l Table I were evaluated in our colony of hoii,seflies(lllirsca domestica L.). The method used was that previously reportd.1 All compounds were mixed dry in the feed.
Discussion The most active compounds of this series appear to be 1, 3, and 4. It is interesting that, as in the case of the aziridineacetyl derivatives previously reported, the C, aliphatic compound (1) is more active than the Clo compound (2). This again emphasizes the importance of spacing between the two alkylating functions. However, in contrast to the finding in the aziridineacetyl series, the xylylenediamine derivative 6 is not very active in this curbamoylaziridine series. Compounds 3 arid 4 would appear worthy of further study as chemosterilants, provided iiiaiiirrialiaii tuxiciti is i i ( l t too great. ( 5 ) G . .\, Ilagxi? nnil I,. N. O a e n , .I. Chem. S o c . . 101 (1!45:3). (ti) 1'. Garcia a n d .J, H , \Vuod, J . O r y . Cheni., 26, 4167 (1961). ( 7 ) S. AJalinoa-ski a n d S. 13enhenick. K o c z n i c k i C h e m . . 27, STY l19X3); Chem. Abslr., 49, 1036a (1955).
Toxicity data iii mice with six daily iiitraperitoric.:i I iiijectioiis show that 7 killed two of three micc at 2 . 5 mg/ kg, 1 killed three of three mice a t 2.5 ing hg. a i i t i 6 killed three of three mice at 5 mg l;g. Thcw :irv. t hub, fairly toxic compuritls, coiiaitierahlj. iiiorv ho thiiii the corresponding aziridiiiencetyl cleriv:itivc.y.y Acknowledgment.--This work n a>nupyurtetl by II'uhlic Health Servi rant (;AI-11191. \TTe tvid thrik 1'. Tovar for tanw with the cheniosterilant cvaluatioiii houyeflieb :tiid 1)r. s. ( h r a t l i i i i . 1-t ituto 11:irio Segri, JIilnri, Italy, for thc toxicBity c1ut:i i i i 711
iiiiw. I 8) I. 1: Siiellenlierger, \\ I'linrnia~ol., 10, 60 (1967).
.
\
Skinlier, ~ - n dJ 11 L e t , Y ' o ~ i c d . z1 pi11
A Sjnthesis of llp-Hydrox?estrone ant1 Related 16- and 17-H? droxyestratriene*
la. X = 0 /H b. X=-
"OH
:{, 1l-l>ihydroxyestra-1,3,3( 10)-trienes have beeii prcviously obtained from steroidal 1I-oxjrgenated 1.1dien-3-ones by p j rol! in low yield.' A new and coiiveiiient synthesis of 1lp-hydroxyestrone (4b) from :indrost:~-1-2-die1ie-:3,1 i-dioric (la) iq n o ~ v reported. l ' h c :iv:iilability of Ilp-hydrosj ebtroiie niac-le it suitable for ronvcr4on to dcrivutive. which ma>- be of bi4a, R = R H; X OCH,CH,O o1ogic:rl iiitercst. :imong t hem the 16- :tiid li-hydroxyb, R = R ' = H , X = O Iated ebtrntrienes. c. R = R ' = A c ; X=O The recent discovery of t h e reductive aromatization d. R = C H , R ' = H , X=O of steroidal 1,-2-dien-;3-o1ie~~ w ~ i sapplied t o the 11hydroxydienories 2b aiid 3. \Then l a or l b was rrfluxed with p-toluene~i~lfonic acid and ethylene glycol i i i benzerie, 2a and 2b \yere obtained, respectively. Sclective reduction of the C'-11 ketone 2a with lithium iluiiiiriuni hydride J ielded 3. Reductivc of t h e :rngul:ir niethyl ielth up t u 72%. Hy4Co oritrnst to the reductivc 5 :uoinatization of 3, the 11cu-liydrox3-dienoiie 2b LWS retluccd t o it product in which the rupture of the bolitl tietween carbon atonia 9 arid 10 had probably occurrcd. ];;viderice for this conclusion was obtained from thc iiiiir q e c t r u m of the crude product which euhibitcd p w h for R methyl group :iiitl three hydrogens on :i hiizenc ring. \Vhen 4b n : i s heiitetl TI ith acetic Liiihydritle and 1)j.ritliiic, thv diacetute 4c I\ :I+ obtained which upon t rch:itmc'iit v it ti p-tolueiie~ulfoi~i~~ acid :mJ iwpropenj 1 a c e t a t r J ielded 5. The enol acetate 5 n n i conv w t c d \vith I c ~ i dtc>tr:i:wct:itc i i i :icetic acid t o a mist 11iv of l(i-aec~to\! 1 7 - I , ~ ~ t o iiit (i ~\\hicli ~ t h c b 108 i ~ o i ~ i ( ~ i ~ 6a u : i \ ~ ) r t ~ ~ ~ t ~ i ~ ~ ll(vliictiiiti i ( ~ i ~ ~ i i or I 6a \+it11 litliiu~ir
X =0 /H b, X=-. -OH
2a,
3
8a. R = H
b, R = CH
