GEXERALBASESWITH e-NITROPHENYL ACETATE
M a y 5 > 1958
lized from benzene, yielded pure, optically inactive12 pinocembrin, m.p. 201-203'. A n d . Calcd. for C I ~ H I ~ OC,~ 70.30; : H , 4.72. Found: C, 70.17; H , 4.80; OCHa, 0.00. Identity was confirmed by mixture melting point and infrared spectral comparison with an authentic specimen of pinocembrin.la T h e ultraviolet spectrum was in agreement with that published by Erdtman.'* Attempted molecular weight determination by Rast's method: A portion of a mixture of 13.7 mg. of pinocembrin and 163.5 mg. of camphor melted in a capillary a t 120'. (12) Pinocembrin f r o m pine wood is optically active, [ a ]- 5~G 0 , b u t racemizes o n sublimation [G. Linstedt, A c t a Chem. S c a n d . , 3, 755 (1949)l. (13) T h e literature records variable melting points f o r pinocembrin. Racemization does n o t result in depression'4; rather, t h e synthetic specimens (inactive) are recorded with t h e highest melting points.15 We are indebted t o D r . Holger E r d t m a n , Royal I n s t i t u t e of Technology, Stockholm, for a specimen of levorotatory pinocembrin. I t s infrared spectrum a n d t h a t of our inactive preparation were superimposable. (14) H. E r d t m a n , Sz'ensk Kem. T i d . , 6 6 , 26 (1944). (1.5) J. Shinoda and S. S a t o , J . Pharm. SOL.( J a p a n ) , 48, 109 (1928).
[ C O S T R I B U T I O N FROM THE
Imidazole Catalysis. IV.
2265
On Dfurther heating the melt turned solid, melting again a t 164 . Acetylation of a sample with acetic anhydridesodium acetate under reflux for 1 hr. followed by recrystallization from boiling ethanol led t o pinocembrin diacetate, m.p. 142-143". T h e same treatment, prolonged fox 5 hr., yielded the 2',4',6'-triacetoxychalcone, m.p. 117-119'. These constants are in agreement with those reported in the literature.14J6 Saponification of the pinocembrin acetate with ethanolic potassium hydroxide revealed two acetyl groups per molecule of 257 (molecular weight of pinocembrin, 256.23). Oxidation of pinocembrin with aqueous alkaline potassium permanganate a t room temperature yielded benzoic acid, purified by sublimation in vacuo, m.p. 122", identified by mixture melting point (no depression) and infrared spectral comparison with an authentic sample.
Acknowledgment.-The authors wish to express their appreciation to the Conselho Nacional de Pesquisas, Brazil, for financial aid. RIO DE
JANEIRO,
BRAZIL
DEPARTMEXT O F BIOCHEMISTRY, YALE
UNIVERSITY]
The Reaction of General Bases with p-Nitrophenyl Acetate in Aqueous Solution B Y THOMAS c. BRUICEAND R.
LtlPINSKI
RECEIVED NOVEMBER 22, 1957 The second-order rate constant for the reaction of OH-, CS-, HPOa--, CHPCOO-, H20, C6HSO-, p-ClC6H40-, p CH30C6H40-, C6HsNH2, p-CHaCsH4R'Hz and ~ - C H ~ C O N H C ~ H I with N H ~ p-nitrophenyl acetate have been determined. \%'hen the log k 2 values for the reaction of the bases studied herein as well as those for the imidazoles and pyridines of a previous study are plotted vs. pK,', in the conventional Bronsted manner, it is found that the nitrogen bases are more efficient nucleophiles toward p-nitrophenyl acetate than are the negatively charged oxygen (or CS-)bases.
As part of a program to study the base catalytic properties of imidazoles, the catalysis of the hydrolysis of p-nitrophenyl acetate (p-NPX) by imidazole and substituted imidazoles was investiCertain observations made during these earlier studies indicated that the imidazoles were, as compared to other general bases, particularly reactive toward p-NPA. It has been the purpose of this study to compare the nucleophilicity of imidazoles and other general bases toward p-NPA. In accord with present concepts of the mechanisms of B ~ c 2 displacement ? reactions a t the ester carbonyl group the over-all reaction of 9-NPA with a general base (B :) would be p-sps
B:
. r
kii
L
o-
1
B
p-NP-
CHPCOB CHaCOB
kiv
+CHaCOOH H20
+ B:
+
In the instance where B : is OH-, the ratio [(ki k i i ) ] is probably quite large since, in the closely allied reaction of OH- with phenyl benzoate in H2018solvent, there is no back incorporation of 0 ' 8 into ester.3 For other bases it is possible that kiii)/(ki
+
(1) For previous papers in this series see: (a) T. C. Bruice a n d G. L. Schmir, THIS J O U R X A L , 79, 1663 (1937); (b) 8 0 , 148 (10.58); (c) G. L. Schmir a n d T. C. Bruice, i b i d . , 8 0 , 1173 (1958). (2) C . K. Ingold, "Structure and Mechanism in Organic Chemistry," Cornell University Press, I t h a c a , N . Y., 1953, p. 754. (3) C. A. B u n t o n and D. iX,Spatcher, J . Chem. SOL.,1070 (1956).
the ratio of forward to reverse rate constants are smaller as was shown by Bender for the alkaline hydrolysis of alkyl benzoates. In the reaction of 9-NPA with imidazoles and pyridines the hydrolysis of the CH3COB intermediates (a~etylimidazole~ and/or acetylimidazo h m saltla and acetylpyridinium sake) is very rapid. Thus the catalytic constant for the reaction of imidazole with p-NPA is sufficiently large to give pseudo first-order kinetics even when the concentration of base was equal to or smaller than that of the substrate.Ia In comparison, for bases such as phenolate and aniline the decomposition of CHZCOB would be rate limiting since the solvolyses of phenyl acetate and acetanilide proceed a l t much lower rates than for p - N P a . VC'hen a large excess of base is employed the accumulation of CH3COB does not effectively lower the concentration of B:. Under these conditions the reaction of all bases with p-NPA may be treated by first-order kinetic expressions thus obviating the necessity of solving expressions for parallel first- and second-order reactions. The value of the second-order rate constant (&) for the displacement reaction i(i.e., B : P-NPX + CHICOB p-NP-) may then be obtained a t any fixed pH and concentration of B : from the expression ( k o b s - &)/(B:) = &, where kohs is the observed pseudo first-order rate constant, k,, is the solvolysis constant in the absence of B:,
+
+
THIS J O U R N A L , 73, 1626 (19.51). ( 5 ) M. L. Bender a n d B. W. T u r n q u e s t , i b i d . , 7 9 , 1652 (1957). ( 6 ) V. Gold, et a l . , J . Chem. SOC.,140G (1953).
(4) L l . I,. Bender,
C.BRUICEAND 11. LAPINSKI
THOMAS
Vol. 80
been shown previously t o be quite small7 and a t the pH values employed the quantity kH+(H3+O)may be ignored. A plot (Fig. 2 ) of kw z's. OH- concentration then gives as its slope k2 for OH- (990 1. mole-' min-') and the intercept divided by the concentration of water affords K Z for HzO (1.54 X 1. mole-' min.-I). The value of kp for OH-, as determined, is in essential agreement to t h a t of 185 1. mole-' min.-' reported by Tommila and Hinshelwood7 for experiments carried out in GOY0 acetone-water, but differs markedly from the value of 30,600 1. mole-' min.-l reported b y Bender and Turnquest when 5% aqueous dioxane was em5 10 15 20 25 30 ployed as ~ o l v e n t . Also, ~ our value of k~ for HzO Concentration of salt, m./L is much smaller than that of 5.9 X 10-5 1. mole-' Fig. 1.-Plots of total concentration of salts z's. log of min.-' reported by these workers. KCN X at p H 8.0, 0 ; K C S X a t pH 7.0, UYth phosphate as buffer, plots of k,bs t i s . total ,d;[KHzPOI KzHP04] X a t PH 8.0,O; [KHzPOd f cyanide concentration afford k ~ 'values of 0.177 1. K2HPOa] X 10-2 at pH 7.0, 0; CHaCOOSa X 1 0 P a t pH mole-' niin.-' and 1.18 1. mole-' min.-' a t PH G.0, x. i . O and 8.0, respectively (Fig. 1). Employing a pKa' of 0.1 for HCN the calculated values of k? and (B:) is the concentration of the catalytically for Ch'- become 1'7.0 and 16.1 1. mole-' min.-', active species of the base [the apparent second- respectively. order rate constant (&') is obtained if (B:) is reI I I placed by (B: BH)]. Alternatively a plot of ' k,,, z's. (B :) gives as its slope kz and as its intercept k,. The values of k z are then a n index of the efficiency of various bases to participate in the displacement of p-NP- from p-SP.4. I
I
I
I
I
I
I
~
+
+
rl---
Experimental Materials.--All inorganic salts employed were of reagent grade. T h e organic compounds were Eastman Kodak Co. 1i;hite Label and were recrystallized or redistilled prior to use. Apparatus.-The constant temperature bath is described in a previous paper.'" Spectrophotometric readings were made with a model DU Beckman spectrophotometer and p H determinations were made with a model G Beckman p H meter. pK,' determinations were made by the method of halfneutralization and serial dilution.lb The second ionization constant for phosphoric acid was determined in a previous study.lc Kinetics.--All reactions were run a t 0.55 di ionic strength provided by buffer and KC1. The solvent was 2 8 . 5 7 , ethanol-water ( v . / v . ) and the temperature 30 f 0.1'. T h e mechanical procedures employed in performing the rate determinations are described in earlier papers.'
Results I n a previous study it was noted that the rate of solvolysis of p-NPA was markedly dependent on the nature and concentration of buffer.Ib I n Table I are recorded the values of k?', kp and k , obtained from plots of hobv E I ~ T .total phosphate and acetate concentration (Fig. 1). TABLE I PK.'
Base
CHsCOOHPO4-HPOI-HP04--
4.7 7.0 7.0 7.0
pH
G.0
k9 1. mole-' niin.-'
L9f
X 109
kw x, 105 min.
0.090 0.095
7 . 0 0.73G 7.5 1 . 1 7 8 . 0 1.38
1.47 1.54
1.52
1
0.72 1.4 1 . 5 1 Zt 0 . 0 2 4 . 0 10 0
The value of k , for the phosphate mid acetate experiments of Table I are given by the expression k,
=
+
k ~ + ( H 3 0 + ) k ~ ~ o ( H 1 0f ) KoH-(OH-)
For the hydrolysis of P-NPX the value of k ~ has t
20
40
80
GU
100
[OH-] X lo', m./l. Fig. ".-The
relation of k, to hydroxide ion con cent ratio^^.
The second-order rate constants for the phenols and anilines were determined from the values of kobs obtained a t two different concentrations of the nucleophile a t p H 8.0 (Table 11). TABLE I1 fiK.'
Base
CgH50 P-ClCeH4Op-CHOCgH4OCeHbXH2 p-CHaC6HdNHz p-CH3COSHCsHINHz
9.98 9.38 i.OB 4.5
5.0 4.4
fin.
1. mole-1 min.-l
19.0 9.6 0.5 .023 ,052 ,020
i3.0 i 1.8 i0.1 f ,001 + ,005 zt ,000
Discussion I n Fig. 3 the log k? values for the reaction of the bases studied herein as well as those for the imidazoles and pyridines of a previous studylb are plotted us. pk',' in the conventional Bronsted manner. Inspection of Fig. 3 reveals that a single linear-free energy diagram does not suffice to correlate all the data. Thus, HP04-- and imidazole are both characterized by pKa' values of '7.0, but their second-order rate constants differ by l o 3 and hydroxide ion (pK-,' 1 5 . i ) is not as good a nucleophile as the anion of G-nitrobenzitIiidazole (pKa' l O . ( i ) . ( 7 ) E. Tommila a n d C. S. Hinshelwood. J . Cliens. S o r . . 1801 (19383. (8) 0. ( h w r o n , A I . D u g g e n and C. J . Grclecki. A n d C h e m . , 24, 989 (1950).
May 5 , 1958
ELECTRONIC STRUCTURE OF BENZOIC ACIDDERIVATIVES
The plots of Fig. 3 are not unusual in that reactions known to proceed by general base catalysis yield separate Bronsted equations for radically different types of basesg It is generally found that all bases characterized by -0-as the attacking nucleophile fall into a single line and this may be noted to be so for the phenols and CH5COO-. The divergence of HPOd--from this line is due to the fact that the pKa' is not truly a measure of its proton affinity. A suitable statistical correction places this point much closer to the plot for other -0- bases. I t may also be noted that the value of log kz for Ha0 falls above that which would be predicted from plots for -0- and 3N: species, but the value of log kz for OH- is considerably lower than expected. I t is usual to have the value of k , for HzO near to that expected from the Bronsted plot, but k , for OH- is generally lower. Probably of greatest interest is the magnitude of the essentially parallel displacement of the lines connecting the points for bases of similar type from the Bronsted plot (log k z = 0.8pKa' - 4.3) for the imidazoles and the decidedly greater nucleophilicity of the nitrogen as compared to the negative oxygen (and CN-) bases when the affinity for the proton is used as standard. The inability to correlate displacement reactions on carbon to pKa' has been treated by Swain and Scott'o who suggest the equation log k/ko = sn for non-solvolytic nucleophilic displacement reactions on carbon. According to Swain, plots of the log k2 relative to water (;.e., log k/ko) ns. derived nucleophilic constants ( n ) afford linear plots with slope s. When the equation of Swain is applied to the bases studied herein for which valtles of n are available (CH3COO-, pyridine, HP04--, OH- aniline and CN-) a value of s = 1.16 is obtained and the median deviation is 0.6 n unit. The major deviant is OH- (3.4 n units). Swain noted a large deviation for OH- (3.74 n units) in its reaction with Ppropiolactone and suggested this to be due to the particularly relative effectiveness of OH- as a nu(9) R . P. Bell, "Acid-Base Catalysis," Oxford University Press, London, 1911, C h a p t . V. (IO) C . G. Swain and C. B . S c o t t , T H I S J O U R N A L , 75, 141 (1953).
[CONTRIBUTION F R O M
THE
I
I
I
I
I
I
2267 I
1
-
2 1-
0 4 M
3
-1
-
-2 -
-4
c
4 I
0
2
I
4
I
I
6
8
I
1 0 1 2 1 4
PKa'. Fig. 3.-A Bronsted type plot of log k1 v s . pK,' for the reaction of general bases with p-nitrophengl acetate.
cleophile in displacement reactions on the ester carbonyl group. A derived value of n = 8.0 for OHfrom the P-propiolactone rate data brings the point for the reaction of OH- with p-NPX into line with the other nucleophiles studied. The application of the more recent dual basicity equation of Edwards" corrects for the large deviation of OH- by allowing suitable weighting of pKa' values in comparison with the nucleophilic constant, but the plot then acquires the same characteristics as the Bronsted plot (Fig. 3). Acknowledgment.-This work was supported by a grant from the Institute of Arthritis and Metabolic Diseases, National Institutes of Health. (11) J. 0. Edwards, i b i d . , 76, I540 (1954); 78, 1819 (1956).
SEWHAVEN,COSNECTICUT
FACULTY O F ENGINEERING, KYOTO USIVERSITY]
Electronic Structure and Auxin Activity of Benzoic Acid Derivatives BY KENICHIFUKUI, CHIKAYOSHI NAGAT-4 AND TEIJIROYONEZAWA RECEIVEDMARCH18, 1957 The rr-elxtron distribution of various benzoic acid derivatives has been calculated by a molecular orbital tnetl-od. A distinct parallelism is found between the electronic structure and t h e auxin activity of these compounds. A discussion of the mechanism of plant growth action is given. X strong resemblance is pointed out between the plant growth action of these compounds and t h e carcinogenic action of aromatic compounds.
Since the discovery of the natural plant growth substance, indole-3-acetic acid, numerous active substances have been synthesized, and in order to elucidate the mechanism of hormonal action of these compounds, many have been made. (1) R . &I. M u i r , C. Hansch a n d A. H. Gallup, Plant Physiol., 24, 359 (1949); C. H . Hansch and R . M . M u i r , ibid., 25, 389 (1950); R . 11. RIuir and C . Hansch, ibid., 28, 218 (1953). (2) R . L . \\:ah, J . Sci. Food A B V . 101 , (1951).
The mechanism of the action of these plant growth hormones nevertheless has remained elusive. (3) R . &I. Muir a n d C. Hansch, Plant Physiol., 26, 369 (1951). (4) C . H a n s c h , R . h l . h l u i r a n d R . L . hletzenberg,ibi~.,26,812(1951). (5) J. M. F. L e a p e r a n d J. R. Bishop, Bot. G a z . , 112, 280 (I
