141
NOTES
January 1966
TABLE I 5-NITROGRbMINES
o z N ~ &.c H z R H
-Found, C H
49
6 3 . 1 6 93
63,s 6.81
68 3c
65.4 i . 6 9 15.3 6 7 . 3 8 . 3 1 13 8
6i.O
7 . 4 5 15 2 8.18 14.1
161-1 63
82
63.7
6.16
17.1
63.9
6.36
150-152
72
64.9
6.61
16.2
64.8
6.68 15.9
1.78-2.21
C S S depremion, low carriage
150-153
33
59.8 5.78 16.1
59.8
5.86
15.9
8.91-14,l
Decreased activity, low carriage
92-94
78
60 3
31.p.,
70
O C .
135-137 5 96-99 80-93
-a -
e
0
n
--S=NCH, --SwNCH. A
C,,H,
9C
108-112
-.3100
CNS depression, ataxia, motor deficit
- N E N C H ? C,H,
147-149
65
75.0 7.55 1 7 . 5
74.5 7.56 1 7 . 1
56.2
CNS depression
-ha-COOH
190-193
48
64.3 7.33 1 6 . 1
64.8 7.00 15.6
>200
CNS stimulation
The low yield is due to difficulty of separation from polymeric material.
The 5-nitrogramines mere prepared by the usual hlannich procedure with 5-nitroindole, formaldehyde, and a secondary aliphatic amine in aqueous acetic acid according to Cavallini and Ravenna,' who prepared 5nitrogramine itself. The 5-aminogramines were prepared by platinum oxide catalyzed hydrogenation of the nitro compounds a t atmospheric pressure. S o hydrogenolysis of the dialkylaminomethyl group to form skatoles was observed as reported by Xerchand.* (7) G. Cavallini and F. Ravenna, Farmaco (Pavia), Ed. Sci., 13, 105 (1958).
The 5-nitrograniines (Table I and 11),when tested in the general behavioral screen with mice, showed mainly CNS depression. However, the toxicities of these compounds were rather high. It is interesting that an increase in the carbon-chain length lowers the toxicity as seen in the first four compounds of Table I. The 5aminogramines also showed a decrease in toxicity, but in general the compounds mere not sufficiently active to be of interest. (8) B. hlerchand, Chem. Ber., 95, 577 (1962).
Experimental Section
5-Nitro-3-dialkylaminomethylindoles.----'~l1~~so ~ O ~ I I ~ C J Iwr(1 I I I ~ r re pared from 5-nitroindole by the general procedure of Cavallirii arid Ilavenna,7 who prepared 5-nitrogramine. The amines were separated from accompanying polymeric material either by estraction into hot 6 S HCI, followed by precipit,ation with a r n moiiia, or by recrystallization from toluene or ethanol. 5-Amino-3-dialkylaminomethylindoles.---Theoorrespondiiig nmiiiograniines were prepared by low-pressure hydrogenation of t lie iiitro compounds over platiiiuni oxide in ethaiiol. The amiiio c~ornpounduwere somewhat unstable arid difirnll t o obtain pure. For thib reason not all of t h e nitrogrumines were suc.cw.ii'ully 1'~JllVCrtedto their amino analogs:. The 5-amiiio c,ompoundi;:w w c rwryslallized from benzene and c lohesane misturer. So tendency towards hydrogenolyais of the dialkylamino moiety TWC observed as evidenced by the eoii,~umptioii( i f onlj- 3 ecluiv. of hydrogen iri each case. 3Ielting points, yields, arid analytical data for all the new conipourids prepared are presented in Tables I :ind 11.
~
Acknowledgment. --Wo n.i.4i t o thank Dr. Samuel Ycrgusoii and his staff for the inousc behavioral data atid toxicities. Experimental Sections
Substitution i n the Hydantoin Ring. Bicyclo[S. 3.0loctane Derivatives
111.
7,7a-Dihydro-7a-methyl-l H-pyrroio [ 1,2-c]imidazole-l,3,5(2H,GH)-trione (IIa).---Three grams (0.02 mole) of I a l was dissolved in 50 ml. of hot 1,1,2,2-tetrachloroethane,and 1.5 g. (0.01 mole) of €',Os was added quickly. The mixture was refluxed 2 hr. and then filtered from the charred residue. TTpoii cvoliiig the filtrate, I l a precipitated in 85
