the syntliesis of IIa. From 0.4-0.5 niole of acids Ib and I C werc obtained SO-S5%', yields of liquid esters IIb [bp 88-92' (12 nim)] and I I c [bp 101-112' (12 mni)], respectively. For aiialysw t h r , crude esters were redistilled several times at reduced prersiw 1.42% and center c:ori;jtant-boilingfractious were c(Jllect,ed; )i% fur IIh, 1.4333 for infrared bands I neat) at 1775 t .i (st,rong, C = O ) and = 2 mi-' (weak, C:=:;L). .tnuZ. Calcd for C~F€l,?u'Oy: C, 55.47; 11, 8.7:;; N , b.(19 I:ound for IIb: CJ, 55.55: H, 8.67; S , 7 . 5 9 . Calcd for C d l ~ NO,: C, 59.87: 1-1, 9.52; Y, 6.96. Foiintl for IIc: C, 39.23; IT, 9.46; N, 6.72. 2-(Isopropylideneaminooxy)-1-alkanols (III).--Tii a11iw-cold solution of 22 g (0.127 mole) of ester I I b in 500 ml of :inhydrou. ether was added, iii five portions and with stirring, 3.4 g (O.OS9 rnole) of solid T.i.4lHa. The reaction mixture was stirred 1 tir longer, :illowed to .tmd at room temperature overnight, a11d i the same fashion as used in the preparation uf g (78';;) of IIIb, bp 83-86" (13 mm). Aftrr llations an analyt ical sample wa5 obtained : ed bards (neat) at 3450 (OH) arid 1640 cnl-' for CiII15XCh: C', 37.90; Ifj 10.41; N, 9.G. C, 57.97; H, 10.54; N, 9.34. 1,ikewise from *50 g (0.25 mole) of eiter I l c and 6.4 g (0.17 rnole) of I,i.klHr was obtained 34.9 g (80:;:) of IIIc, bp 93-103" (21 I n m J . After three more dktillationz there resulted an :tnalytical Pample, bp 11:3-118.3' (13 mm), n'% 1.4455, signific.ttrit infrared bands (neat) a t 3390 (OH) arid 1630 vn1-l (C==Xl. .1nuI. Calcd for CsHl,pu'O~: C, 62.39; 13, 11.05; S , 8.09 Foiuid: C, 62.07; H, 10.90; N, 7.66. 2 4 2,4,5,7-Tetranitro-S-fluorenylideneaminooxy)alkanoic Acids (IV).--The procedure followed that, used by Newniau and I,ut,z3 for synthesis of IVa. 4 rnixt,ure of 23.1 g of 2,4,5,7-tetrailitrofluorenone, 15.4 g of Ib, 2.5 g of p-toluenesulfonic acid, and 175 1111of glacial acetic acid was refluxed, cooled, and diluted wit11 water. The precipitate was washed wit,h dilute acetic acid, dissolved in 80 ml of propionic acid, and reprecipitated by additiuii of an equal volume of water to this hot solution; yield 24.8 g (8455)of IVb, mp 166-169". For analysis, IVb was converted t o the IVb-benzene molecular compound (by repeated recrystallization from benzene), obtained as pale yellow prisms or powder: nip 126--12i70,stable to drying for 8 hr at 25" (0.1 mm). I . Calcd for Cl7Rl1N&~CSHG:C:, 51.21; H, 3.15; S . Found: C, 51.20; H, 3.11; S , 13.02. ila1.1~I C was converted t,o IVc (907, yield), mp 211.521 (io.Pour recrystallizations froiii tmizerie gave yellon- p r i s m of IVc-benzene molecular compound, nip 216-217.5", stable to dr>-iiigfor 30 hr a t 56" (0.05 mml. 1 ~ 1 1 . C:itlcd for C',crlT,jSaOl, ~ ( ' J l l , : (I, . X . S 2 : 11, : j . i 9 : N , . l~l~lllid:c:, 52.68: 11, ::.n:r: s,12.16. ~ O L I I I ~ :
Compounds Affecting the Central Nervous System. 11. Substituted L ,2,3,4-Tetrahydropyrido [4,3-b] indoles I:. G. W. S P I L K E ~ T ~ Smith Klzne and Fi rnc h Luborulor lea Lltl., Welwyn Garden City, Hertfordshzre, England I2cceinecl Jultj 6 , 1962
The I ,~,3,-l-tet,rahydropyri~(~ [4,3-b ]indole (y-c:irboliiie) ring Rysteni, in contrast to the @-carbolinenucleus, lia,q been little investigated :is :t source of biologically active compounds. S2 quaternary salts of this ring system were investigated2 :is potential curarizing agents, some of them having a potency of about onefifth that of &tubocurarine. Horlein3 prepared 3I I :\llm and Hanlsurys Ltci., W a r ? , lIertfordnhire, England. 1) (si) V. Ih~~~kleIiir*cla nn(1 ( ' . \itis\\ (1950); (17) V. Kosnarti a n d . P a l a d o , LZ. P h i m i . Jtnl.. 8 4 , 644 (19.541, (,'hem. . t h s t r . , 49, 1:3'38i (1'3.5: (:3) [I. lldrlr~in.C h ~ m .Re , l ! l , ~ l l , i 2 1 , i i I ,l!l.72),i:j:j,t
Noms
May 1966
437
TABLEI SUBSTITUTED 1,2,3,4-TETRAHYDROPYHIDO [4,3-b]INDOLES
R Hecrystn
-c,
801-
K,
RI
R3
venta
Mp,
O C
Formula
Calcd
%-Found
-n, Calcd
%--Found
7 - ~ , Calcd
%-Found
CIIJ H H CzH, H H CsHjCH2 H H C6HbCHzCHn H H C ~ H ~ C H Z C CsHj H~ H C~HF,CH~CH? CH3 H C6HjCH2 CsH, H CsHjCH2 CGHLCH?H C,H,CH,CH, CaHjCHy H H Br CH3
3 169-171b CizHi4W2 77.4 77.8 7.59 7.41 15.05 15.25 2 125-126 C13H16x2 78.0 78.0 8 . 0 5 7.92 14.0 14.1 1 161 CUHISNZ 82.4 82.2 6.93 6 . 9 3 10.7 10.i5 1 166.5-168 CigHzoN? 82.6 82.7 7.29 7.60 10.1 10.0 1 124.5-125.5 C2~H24N2 85.2 85.2 6 . 8 6 6.88 8.0 8.0 2 65-66 C20HZ3X2 82.7 82.8 7 . 6 4 7.56 9.7 9.8 2 92.5-94.5 C24H22S2 85.2 85.3 6.55 6.71 8.3 8.4 3 154.5-155 C2jHz4N2 85.2 85.1 6 . 8 6 6.98 7.95 8.0 1 86-88 C26H26X2 85.2 84.9 7.15 6.93 7.7 8.0 1 165.5-167 C12H13BrN2c 54.35 53.3 4.94 4.95 10.6 10.65 4 264 Cl2Hl3Br?J2~ HC1, 0.5H?Od 4 6 . 4 46.4 4.87 4 . 5 1 9.0 9.0 H 5 195-197 Cz?H,iN2 HCle 74.4 74.3 7.67 7.95 7.9 7.9 C6HjCH2 n-C4Hg a Solvents: 1, ethanol; 2, petroleum-ether (bp 40-60"); 3, benzene-petroleum ether; 4, water; 5, ethanol-ether. A. H. Cook Anal. Calcd: Br, 30.1. Foiind: Br, 30.4. Anal. Calcd: C1, 11.4. and K. J. Reed [ J . Chem. Soc., 399 (1945)l givemp 171-172". Found: C1, 11.5. "-4nal. Calcd: C1, 10.0. Found: C1, 10.0.
K1
R2
C2I-Ij C2Hj
Rs
n
Itecrystn solventa
Alp or brr (mm), O C
--c, Formula
140-144 (0.05) CisHziN3 1 140.5-142 C18H27N3 '2C4H404 CyHj CzHj 2 CsHjCH:! 192-196 (0.05) Cz4H3iN3 2 158-159 C24H31Y3.2C4H404 2 CH, 168-170 ( 0 . 1 ) CigH2iNs 2 151.5-152,5 CigH27X3.2C4H404 245-250 ( 0 . 1 ) C2jH33N3 CyITj CpIlj 2 C6H>(C112)2 2 162.5-164 Cz,H,,N, .2C4H404 CH,U hAK 3 CH3 207-210 ( 0 . 1 ) C~OH~OX~ 3 159-161 C20H30N4.3C4H404 CH, 154-159 (0.05)b C1&?;3 CH, CH, 2 2 169-170" CisH23Xa. 2C4H404 2 CH, 175-180 ( 0 . 5 ) CisH,,Xj, 2 136.5-137.5 CisH2~N3.2C4H404 Solvents: 1, methyl alcohol-ether; 2, ethyl alcohol-ether; 3, ethyl alcohol. (2.5 mm). Lit.b mp 164-165'. 2
CII,
test the 5position of the nucleus should be unsubstituted. When this position was unsubstituted optimal activity resulted when the group in the 2-position was inethyl. Experimental Section Substituted 1,2,3,4-Tetrahydropyrido[4,3-b]indoles (Table I). A.-A mixture of the appropriately substituted 4-piperidone (0.1 mole), the appropriately substituted phenylhydrazine hgdrochloride (14.6 g, 0.1 mole), and alcohol saturated with HC1 a t ( 1 2 ) M?ltinp ~ i o i n t swere recorded iising a n electrothermal meltine point ai)i>aratiis comprising a gas heater block and a thermometer calihrated for exposed stem. AIicroanalyses are by Llr. .\I. Graham and spectra b y l l i s s E;. V. Egginton. T h e ultraviolet a n d infrared spectra of all the products \vas recorded.
Calcd
%-Found
---H) Calcd
%Found
-5, Calcd
