259 1
COMMUNCATIONS TO THE EDITOR
May 20, 1938
(11,R = 0=, no 1,2-unsaturation), m.p. 254-255', [c~]*~D +36", 2.75, 5.90 and 6.18 P, kz2H 234 (22,900), 274 (6500) and 325 mp (53001, (found for C1;HlSNO5: C, 64.42; H , 5.96), and oxoapohaemanthidine, (111, R = O=), m.p. 142-145", [ c Y ] ~ ~+230°, D ' ' : : :A 5.88 and 6.20 1.1, 236 (24,200), 276 (6000) and 322 mp (5000), (found for CI6H13NO4: C, 67.89; H, 4.53), respectively. These oxidation products represent three compounds of proven structure which, for theoretical reasons, should possess the properties of amino ketones rather than lactams.* Preliminary evidence supporting this view includes the positions of the infrared carbonyl maxima, the ultraviolet spectra and the facile reduction in methanol of each oxo compound to the respective starting alcohol by sodium borohydride.
pounds I, 11, and 111. The results obtained in aqueous solution a t 25' are plotted in Fig. 1 and show that I and I1 hydrolyze in the p H range 3-9
(8) C j . t h e reported synthesis of 2-quinuclidone, L. N. Yakhontov and hl. V Rubtsov, Zhur. Obshchei K h i m . , '27, 72 (1957); C.A., 61, 12085b (1957). (9) Visiting Scientist, National Heart Institute, on leave from the University of Osaka, Osaka, Japan.
LABORATORY OF CHEMISTRY s. U Y E O ~ OF NATURAL PRODUCTS H. M. FALES NATIOXAL HEARTISSTITUTE R. J. HICHET BETHESDA 14, MARYLAND W. C. WILDMAN RECEIVED APRIL2 , 1958 INTRAMOLECULAR BIFUNCTIONAL CATALYSIS OF ESTER HYDROLYSIS
Sir: It has been demonstrated previously t h a t the solvolysis of phenyl esters is powerfully catalyzed by suitably spaced neighboring ionized carboxyl group^.^,^,^ Such reactions should be further accelerated, if the ester carries a second substituent which will stabilize the transition state, e.g., by hydrogen bonding or by ion pair formation. The principle is similar to the "bifunctional catalysis" of Swain and Brown4 except that all three functional groups form part of a single molecule. We have tested this assumption by comparing the PH dependence of the solvolysis rate of com-
1
w
I 4
2
0
I
I
I
I
6
q
10
I2
PH,
data for com-
Fig. 1.-Hydrolysis rate constants a t 25'; pound I from reference 3.
a t rates proportional to their carboxyl ionization, while I11 hydrolyzes a t a rate corresponding to the concentration of the singly ionized species, assuming pK = 3.62 and 4.5 for the salicylic and succinic carboxyls, respectively. Two pathways are pos0
0
0
/I
0
0
0
I,'1
/I
A/CoH I
N
\
H.0
O
11 0
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C-CHz
B
It
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It
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I11 (1) J. D. Chanley, E. M. Gindler and H. Sobotka, THISJOURNAL, 74, 4347 (1952). (2) (a) H. Morawetz and P. E. Zimmering, J. P h y s . Chem., 68, 753 (1954). (b) P. E. Zimmering, E. W. Westhead, Jr., and H. Marawetz, Biochim. Biophys. Acla, 25, 376 (1957). (3) E. R. Garrett, THISJ O U R N A L , 79, 3401 (1957). (4) C. G. Swain and J. F. Brown, Jr., i b i d . , 74, 2538 (1952).
t0-CEO 9
2
sible and no distinction may be made between them from kinetic data. If the reaction proceeds exclusively through A, this intermediate would decompose 24,000 times as fast as ionized I which has the carboxylate in the same position but lacks the second, un-ionized, carboxyl. Conversely, if the reaction proceeds through B, this intermediate is 66 times as reactive as ionized 11. Intramolecular catalysis by neighboring functional groups, such as observed with compound
2392
COMMUNIC.%TIONS TO THE EDITOR
111, is of interest because of its analogy t o the high reactivity of enzyme-substrate c ~ m p l e x e s . * ~ J , ~ Acknowledgment.-This research was supported by the U. S. S r m y Office of Ordnance Research. Helpful discussions with Dr. J. F. Brown, Jr., and Professors A I . L. Bender, C. G. Swain and F. H. If-estheimer are gratefully acknowledged. ( 5 ) H. M o r a a e t z and E. M. Westhead, Jr., J. Polymer 2 i 3 (1955). (6) 11. I, Bender, TaIs JOCJRNAI.. 1 9 , 1238 (1957). D E P A R T M E N T O F CHEMISTRY P O L Y T E C H N I C INSTITCTE O F B R O O K L Y N
BROOKLYY1, SEW YORK
Sci., 16,
ET, M O R A W E T Z 1, ORI
