Noms
Vol. '74
~ n a i i nof ~ the hemlock alkaloid (+)-coniine ( I ) , to the S-bromo coinpound (11) and thence by sulfuric acitl to \ - i-octahydropyrrocoline proceeds
tion spectra of this substancc arid of $-melibiose dihydrate nlay be compared in Fig. 1. X-Ray diffraction datal7: 8.96 (M), 7.70 ( W V ) , 6.80 (\vi, 6.30 (S), 5.40 (VW),5.13 (VS),4.91 (V\l-), 4.63 ( S ) , 4.41 (VS),4.11 (S),3.94 ( A I ) ,
IV with retention of configuration at the asyminetric carbon. The changes involved in the conversion would not be expected to result in inversion a t the a-carbon, but i t seemed advisable to determine whether any appreciable racemization had occurred. The rotation reported by Lellniann2 for the active octahydropyrrocoline obtained from (+)-coniine was - i . 8 ' . We have resolved synthetic octahydropyrrocoline by means of dibenzoyl-D-tartaric acid and have obtained active octahydropyrrocoline of constant maximum rotation, [ a I s i ~ ) --T.R!I'. I t is thus apparent that the Lellmann product was of optical purity and identical configuration with [+j-coniine. Since (+j-coniine has been related t u D ( + j-pipecolinic it follows that levorotatory octahydropyrrocoline has the D-configuration, wherein the designation '(D" acquires nieanirig when represented by the pro jection formula 111 (rf. 1V;i.
Crystals of a-melibiose monohydrate, growi iii ;t riscoti; aqueous sirup, were negative in sign and showed, TZ)OD, a = 1,524, 6 = 1.542, = 1.359, 2\- = 86" and birefringence = 0 ,035. .11zal. Calcd. for CIZH&~.H?O: C , 40.00; H , 0.7j; HzO, 5.00. Found: C, 4 0 . l i ; H , 6.70; loss of lvt. ill vacuo a t loo", 4.99. Kecrystallizatiori of 1 g. of tnclibiose from 100 nil. of a n hydrous methanol afforded 0.35 g . of essentially anhydrous a-melibiose ( O . l i % loss in vacuo a t 100'). On exposure to air this approached a monohydrate iii composition, Acetylation of a-Melibiose.-oi-Melibiose ( 2 g . containing 4.2y0water was acetylated in the usual fashion with acetic anhydride and sodium acetate. The crystalline product (3.3 g., 82%), recrystallized from 8 parts of absolute alcohol, showed [ C L J ~ D+104.3" in chloroform (c 0.82) and melted a t 177-178" either alone or it1 atliiiixture with authentic $-inelibiosc octaacetatc.
-,
,
x.,
(17) Interplanar spacing. C u K U radiation (nickel filter); camera diameter 14 32 cm. Relative intensity estimated visually VS = very strong, S = strong, ;If = moderately strong, W = weak, T'W = very weak and b designates broad, unresolved line or lines.
Experimental
Mono-( - 1-octahydropyrrocoline Dibenzoyl-D-tartrate.-
.A solutioii of 112.8 g . (0.3 mole) of dibenzoyl-D-tartaric acic iiionohydratefiin 400 nil. of inethanol was mixed with 3 i . o g. (0.3 mole) of synthetic octahydropyrrocoline.? The white crystalliiie niass which formed a fern minutes after inixiiig was removed by filtration and washed with cold iiicthanol. This material was rccrystallized from 4 liters of methanol. After five additional recrystallizations frmi methanol, 33.S g. of large colorless prisms was obtained, ni.p. 1633-164' with decomposition; [ a ]*'D --T5.8' (( (),600,met haiiol). :liial. Calcd. for Cz~HzvKOs:C , 64.58; H , 6.05; S , 3.89. Found: C, 64.29; H,6.16; S , 2 . 9 3 . (-)-Octahydropyrrocolie (III).-A slurry of 31.4 g. of inoiio-( - )-octahydropyrrocoline dibenzoyl-D-tartrate and 200 ml. of 3 N hydrochloric acid was shaken for 30 minutes. The oil which separated solidified on addition of a few crys-
S A T I O N A L 1XSTITUTE O F *kR.THRITIS A N D METABOLIC DISEASES S A T I O S A L INSTITL-TES O F HEAI. TII, PUBI,IC HE.91.11I SbRYICb
I;III)BRAL SECURITY r20r;sc~ RWHESILI, & . ~ A R Y L A ~ I >
Octahydropyrrocoline : Resolution and Configuration IiY xELSO\ J
L h O h A R D AND \yILLI.4M
J
1lIL)DLETOh
HCCFIIF 11J U L Y7, 1952
The establishment of the stereochemical configuration for (-)-octahydropyrrocoline (111)' is important because of the occurrence of this nucleus o r moiety in many of the papilionaceous and solanaceous alkaloids. Such establishment is possible i t we can bc assured that the conversion by Lell( 1) Alterndll>e ndini i ~ i c y c I u [ 43 O]noriane
o cmiciiiie
i ~ i i ~ c i i t l i r l i r i ci i i t l
I
r
l
( 2 ) E . Lelimann, Ber., 23, 2141 (1890).
~
(3) "The Alkaloids. Chemistry and Physiology," edited by R. €1. F. hlanske and H . L. Holmes, Academic Press, Inc., New York, N. Y . , Vrrl. 1, 1!13O ] ) I ) . 215, 217, 2 2 5 , 2 2 6 . 1 ii I V . Leithc, Bci , 66, 927 (1932). .\, S c i i b c r R e r , A d ~ . i i i i c e i~i i I'ioteiii C h c i n i ~ l i y 4 , , ?!I7 il!i4Xi C I.. B u t l c r and I,. 11. Cictchrr,'C"xs J O U R N A L , 6 6 , P W ; 1,1;13:$1. ' 7 1 1'.B o ~ k e l i i c i ~ aiid i c S. K o t l i d i i l d , i b i d . , 70, SO4 [1!)48:
NOTES
Nov. 20, 1952
tals of dibetizoyl-D-tartaric acid monohydrate. The solid was removed by filtration, and the filtrate was cooled and made basic with cold 33% potassium hydroxide solution. The alkaline solution was extracted with ether and the ether extracts were dries. The ether was evaporated and the residue was distilled under reduced pressure, yielding 5.1 g. of (-)-octahydropyrrocoline, b.p. 58-59' (18 m m . ) , T Z ~ D 1.4712, [CY]~'D -7.89'. Anal. Calcd. forC8H15S:C, 76.74; H, 12.08; S,11.19. Found: C, 76.50; H , 11.96; S , 11.40. THENOYESCHEMICAL LABORATORY UNIVERSITY OF ILLINOIS URBASA,ILLIXOIS
Partition Studies. VIII. Silver Complexes of Aromatic Amines BY CALVINGOLUMBIC RECEIVED JUNE 11, 1952
Silver ion reacts like a generalized acid with a variety of olefinic1V2 and aromatic corn pound^^-^ according to the equations Ag+ Agf
+B
+ AgB
__
AgB+
therefore, to study the argentation of aniline and its methyl-substituted homologs by the distribution method'^^ in which a high (Ag+)t/(B)t ratio can be conveniently maintained. To apply the distribution method, partition coefficients were determined in the presence and in the absence of the complexing agent. The k' values recorded in Table I are the partition coefficients for distribution of aniline and its methylsubstituted homologs between cyclohexane and aqueous silver nitrate solutions in which ionic strength was maintained a t unity by addition of appropriate amounts of potassium nitrate. The k-values are the partition coefficients of the amines for distribution between cyclohexane and 1 molar potassium nitrate solution. In all distributions, the silver ion concentration was much greater than the total concentration of amine (0.005 Ab!). Under these conditions, the equilibrium constant, K , for the formation of a 1: 1 complex exclusively (equation 1) can be calculated by the equation6
(1)
K2
(2)
AgZB + *
+
With nitrogen bases, complexes of the 1 : 2 type, ,~ AgBzf, rather than AgzB++, are f ~ r r n e d . ~This observation was based upon electrometric measurements of solutions in which the ratio ( A g + ) t o t a l / For a high ( B ) t o t a l was usually less than unity. value of this ratio, i t seemed likely that aromatic amines would form 2 : 1 complexes because of the possibility that a second silver ion could coordinate with the aromatic nucleus. It was of interest,
K = ( k / k ' - l)/(Ag+)t
k
moles/ltter
K
k'
K = KI
.50 .75 0.00 .05 .IO .20 .25
.35 .50 .75
,
show a marked increase with silver ion concentration, and K was a linear function of the silver ion concentration for all compounds investigated; this was in accordance with equation 4. From the intercepts and slopes of these straight lines, K , I
k
k'
K
k
30.4 31.2 35.0 37.9 41.2 48.4
Pi-Methylaiiilirie 25.2
K
k'
k
k u - Toluidine
5.i3 0.54 .33 .17 .13 .088 .054
(41
h s indicated in Table I, the calculated K values
u-Toluidine
1.36
+ KiK4Ag-h
CYCLOHEXASE AND U'ATER I N THE PRESENCE O F SILVER A-ITRATE A I
Atiiline 0.00 .05 .10 .20 .25 .35
(3)
On. the other hand, if the complexing action proceeds partly to the 2 : 1 stage (equation 2 ) , K is not independent of (Xg+)t and equation 4 applies.'
TABLE
DISTRIBUTION OF ANILINESBETWEEN &+It,
5777
25.0''
k'
K
p-Toluidine
4.84
4.6%
1.22
37.0
1.10
34.0
0.90
41.3
0.48 .32 .20
43.8 48.3 55.2
0.43 .28 .17
41.1 46.5 53.3
.35 .24 .15 .08
48.8 52.2 59.6 71 .O
3,5-Xyliditic
2,Ci-Xylitliite
22.0
34.7
12,.54
10.2
3.77
48.4
5.58
52.2
6.50 4.77 3.28 1.97
11.5 12.3 13.4 15.7
1.54
53.1
0.65 0.37
65.7 78.0
1.95 1.22 0.73
67.2 78.4 93.0
(1) S. Winstein and H. J. Lucas, THIS JOURNAL, 60,836 (1938). (2) F. R. Hepner. K.N. Trueblood and H. J. Lucas, ibid.,74,1333 (1952). (3) L. J. Andrews and R. M. Keefer, ibid., 71, 3113 (1950); 71, . 5034 (1950); 78, 5733 (1951). (4) P. L. Nichols, ibid., 74, 1091 (1952). ( 5 ) C. Golumbic and S. Weller, ibid.,74,3739 (1952). (6) J. Bjerrum. "Metal Ammine Formation in Aqueous Solution," P. Haase and Son, Copenhagen, 1941, p. 298. (7) R. J. Bruehlman and F. H . Verhoek, THISJOURNAL, 70, 1401 (1948).
and KZ8 were evaluated and are summarized in Table 11, together with the known acidic dissociation constants ( P K a values) of the bases. The observed t r a d s in the K1 and Kz values appear to be most consistent with the assumption that the first silver ion coordinates with the amino nitrogen and the second with the aromatic nucleus. (8) For a discussion of the relation between these constants and the true thermodynamic equilibrium constants see ref. 2.
