J. Org. Chem. 1980,45, 3103-3107
0.2-1
I
n
-IL
0.4
l
+I 0 CHARGE ON R
-I RS-
0 c:
R-S-
-
I
OF Figure 4. Plot of the cidculated log k value minus the measured log k value vs. the charge on the R group of the attacking RS-. sulfur atoms may be attacked by the nucleophilic thiol anion as shown in striictures A and B. By use of the value RS-
s-s-
I
S NO^
S-S--CH~CH$H~
A I
+I NH3
NO2
A
B
of PCT and that for the leaving group (PLG= -P,,, = -0.5) and by use of the fact that aryl thiol anions leave sixfold faster than alkyl thiol. anions,2a calculation of the relative rates of attack at the two sites may be made. The ratio of rates of the desired reaction (A) to the undesired reaction (B)is calculated to be about 15 in the worst case. This small percentage of attack on the wrong sulfur has no effect on the rate if the entering and leaving thiol are identical or similar in pKa. In the few cases where the small amount of new mixed disulfide would have differed substantially in rate from the starting mixed disulfide, semilog plots of the absorbance data were made. The linear plots found ensured that there was very little, if any, error in the measured rate due to initial attack at the wrong sulfur.
3103
The points for the variously charged disulfides and thiols exhibit small but significant deviations from the Brernsted type plots found for the uncharged systems. The deviations are plotted in Figure 4 and show a pattern that indicates that pK, values alone provide a good but not perfect index of how the charge will affect the stability of a transition state. The negative charges on R groups destabilize the calibrating ionization reaction of the thiols and the positive charges stabilize the same reaction. The fact that there are negative deviations for negative groups and positive deviations for positively charged groups implies that charge has a proportionally greater effect on transition-state energy than inductive effects when compared to the calibrating ionization reaction. One interesting feature of Figure 4 is that the deviation from uncharged values is greatest when the charge is on the central group rather than on the attacking group and that increasing the distance from the reacting site diminishes the effect of the charge. Coulombic interactions are apparently also evident between attacking and central thiol R groups in the relatively low rates found when both are positively charged. We conclude that predictions of rate constants for the thiol-disulfide interchange reaction in aqueous solution may be in error by as much as a factor of 2.5 when structure-reactivity correlations measured with uncharged substituents are used to predict the rates of those with charged substituents. The effect of these deviations can have a profound effect on the value measured for a reaction. If a series of reactants is used in which the highest pKa reactants are negatively charged and the lowest positively charged, there will be a tendency to tilt the slope of the plot. A total set of deviations of 0.6 log k unit over a range of 3 pK, units would give a (3 value in error by 0.2 and thus give a much different estimate of the degree of bond formation than would be obtained with neutral substituent groups.
Acknowledgment. This work was supported by the National Science Foundation, Grant CHE-78-08723. Registry No. 02NC6H4SH,1849-36-1; (-OzCCH2CH2S)2, 5882320-4; ('H,NCH2CH2S)2, 58823-21-5; (HOCH2CH2S)2, 111-48-8; (-02C(CH2)3S)z9 73873-03-7; 'H3NCH2CH2SSC6HdN02, 73873-04-8; H O C H ~ C H ~ S S C ~ H I N53595-97-4; O~, -O~CCH~CH~SSCBH~NO~, 73891-30-2; -OzC(CH2)3SSCsH4N02,73891-31-3; 'H3NCH2CHZSH, 40302-08-7; HOCHZCH~SH, 60-24-2; -02CCHZCH2SH, 2365-49-3.
Structure-Reactivity Relationships in Nucleophilic Reactions on Cinnamoyl Azide and Phenyl Cinnamates. Kinetic Stability of the Acyl Azide and Relative Leaving Ability of Nitrogen and Oxygen Junghun Suh* and Byung Hyun Lee' Department of Chemistry, Seoul National University, Seoul, Korea Received January 31, 1980
The alkaline hydrolysis and aminolysis of cinnamoyl azide and aryl-substituted phenyl cinnamates and the azidolysis of the phenyl cinnamates have been studied. The positions of the ratedetermining steps in the reactions are identified by the structure-reactivity relationships. The enhanced affinity of azide ion for an acyl carbon compared with its basicity is proposed to account for the observed kinetic stability of cinnamoyl azide toward alkaline hydrolysis and aminolysis. Azide ion resists expulsion from the tetrahedral intermediate more than quinuclidine derivatives but less than phenolates. This is explained in terms of the electron withdrawal as well as electron donation by resonance. Nucleophilic reactions on acyl derivatives, especially esters and amides, have been the subject of extensive 0022-3263/80/1945-3103$01.00/0
studies. The existence of a tetrahedral intermediate with a finite lifetime, the nature of the rate-determining steps, 0 1980 American Chemical Society
3104
J. Org. C'hem., Vol. 45, No. 15, 1980
Suh and Lee
the relative leaving ability of the leaving groups, and the changes in the effective charge on the nucleophilic elements are included among the actively investigated topics in the mechanistic studies of acyl transfer from esters or amides.2-8 A large number of studies on the aminolysis of esters have been performed In particular, ester aminolysis with tertiary amines3,*including imidazoles or pyridines@ has been studied, so that possible ambiguities from proton transfer were avoided and the basicity of the leaving alkoxides was not much different from that of the attacking amines. From these studies, a comparison has been made of the leaving abilities of nitrogen and ~ x y g e n .In ~ reactions with esters, the nitrogen of the tertiary amine acquires a positive charge in the tetrahedral intermediate and destabilizes the resulting amide. Furthermore, the amines used are quite bulky, and the consequent steric effects must be considered. The leaving nitrogen of an acyl azide contains no formal charge or bulky groupis and, thus, is free from the electronic and steric complications. In addition, its basicity (pKHN3 = 4.73) is not much different from that of the leaving groups of activated esters. Resonance stabilization and the consequent double bond character of the C-N bonds of acyl azides (eq 1) are expected to be significant. This 0
11
+
RCN=N=NA
-
0I
C
RC=N-N=N
(1)
B
is because charge creation does not take place, and the negative charge mover3 to the more electronegative element, 0, on going from A to B.9 Thus, acyl azides can be useful as mechanistic probes of acyl-transfer reactions. Kinetic studies on acyl transfer from acyl azides have rarely been reported because acyl azides usually undergo Curtius rearrangement (eq 2).'O However, we have found RC(O)N=N+==N-
--N2
RN=C=O
H2O
3
RNHCOOH RNHz (2) that the derivatives of cinnamoyl azide (1) are quite stable h
+L@
