Equations for Correlation of Nucleophilic Reactivity
Khairal M. Ibne-Rasa University of the Panjab
Lahore, West Pakistan
correlation of the rates of bimolecular nucleophilie substitution reactions has attracted much attention since the pioneering work of Swain and Scott ( 1 ) and the subject has been extensively reviewed during the past few years (9-5). This article presents a simple and critical discussion of the empirical criteria that have been used to correlate nucleophilic reactivities and contains material for ahout two lectures in a physical organic chemistry course for organic majors. For a more comprehensive treatment the excellent reviews of Edwards and Pearson (9) and Bunnett (3) are recommended. Ingold (6) defined nueleophiles as "reagents which act bv donatine their electrons to, or sharing them with, "a foreign atomic nucleus." By this definition not only all bases and ligands but also ordinary reducing agents like Na (metal), Sn2+,and [Fe(CN)s14-, which act by complete transference of their electrons, are nueleophiles or nucleophilie reagents. To the extent that Ingold's definition includes the reducing agents as nucleophiles, it has not found general aeeeptanee. The generally accepted concept (1) is that "both bases and nucleophiles are reagents which have a tendency to form new covalent bonds by sharing their electron pairs." However, the term basicity is used in the thermodynamic sense, while the term nucleophilicity is employed in describing the kinetic behavior. Thus the equilibrium constant K of eqn. (1) is a measure of the basicity of the species B-
is the basic dissociation constant of N-, G and @ are constants for a given temperature, and p and q are statistical factors (7). Still better correlations between nucleophilieities and basicities are observed in the reactions of variously substituted aromatic eompounds when the substituent group is in the nzeta or para position with respect to the nucleophilic atom. For example, for the reaction:
-
K
c BH+HsO (1) whereas the rate constant k of the displacement B-+H30t
reaction of eqn. (2) is a measure of the nucleophilic reactivity of Bk
B-+RX-BR+X-
(2)
i.e., the larger the value of k the greater the nucleophilic strength. The electron pair acceptor atom in an acid-base reaction (eqn. (1)) or in a displacement reaction (eqn. (2)) is called an acid or an eleetrophile, respectively. For a niven nroun of nucleonhiles containinn the same nucleophilic atom, and of which the structural features in the immediate vicinity of the nueleophilic atom are similar, nueleophilicities are well correlated with their basicities. Thus, for example, in the reaction CICHGOO- + N- -. NCH,COOC1(3) where N- is a nucleophile, the rate of reaction with 32 different nucleophiles (carboxylate anions), whose nueleophilic atoms are oxygen, was found t o obey the 6 log Bronsted catalysis law: log (k/q) = log G (K,P/q), where k is the rate constant (eqn. (3)), Kb
- -
-
L
+
+
which involves nucleophilic displacement by the amino nitrogen upon peroxidic oxygen, the rate of reaction with variously p-substituted axiilines was found to give an excellent correlation with the basicities of the anilines (8). Limitations of Correlation
The matter of predicting the relative reactivities of various nucleophilic reagents would have been quite simple if correlations of the above type were universal, because the equilibrium constants for systems in aqueous solutions of the type of eqn. (1) are known for a large number of particles. However, nueleophilicities do not correlate with basicities within a group of nueleophiles if: (1) the nucleophilic atom is not the same, or, (2) the nucleophilic atom is the same but the sterie and electronic environments of the nucleophilie site vary from nueleophile to nucleophile. Thus in the reaction represented by eqn. (3), the Bronsted correlation which held for 32 similarly cow stituted oxygen nueleophiles (carhoxylate anions), eompletely broke down when N- was SOa2- or SzOZ2-. The observed rate of reaction with these sulfur nucleophiles was much larger than that expected from their basicities. The failure of o-substituted aromatic compounds to ohey a nucleophilieity-hasicity correlation in contrast with their nt- and p-analogs is well known; sterie factors dominate in determining the nueleophilicities for o-compounds. An example of the diierenee in the electronic environment around the nucleophilie atom destroying the parallelism between nueleophilieity and basicity is the reactivity of OOH- relative to OH-. Pearson and Edgington (9) have recently shown that in the displacement reaction in eqn. (5a and b), the observed value of the ratio koox-Ikon- is 35 at 25'C in 50% by volume acetone-water medium. Thus; Volume 44, Number 2, February 1967
/
89
OH -
+ Br(C"H8CH10H C;H.CHzOOH + Br-
C~HECHIB~
OOH-
(5s) (5b)
toward spa carbon, OOH- is 35 times as strong a nucleophile as OH-, even though OH- is about lo4 times stronger as a base. Other cases of this type include the greater reactivity of N-phenylhydroxylarnines as compared with the corresponding anilines in their displacement on the peroxidic oxygen of peroxyacetic acid, (8) k m ~ ~ o d k=e 8~ in ~ ,ethanol at 1O0C, and the many examples cited by Jencks and ~arriuolo(10). It is not surprising that nucleophilicity-basicity correlations do not exist except under certain narrow limitations. Basicity is a measure of the thermodynamic affinity of a species toward a proton, and the proton enjoys a certain uniqueness as an electrophile because of the smallness of its size and because it carries a concentrated positive charge. The structural and electronic features of a nucleophie which may seriously iduence its nucleophilic reactivity in d i s placement reactions do not necessarily play an equally significant role in the acid-base equilibria. Relative Nucleophilicities
Since a knowledge of the relative nucleophilicities of various nucleophiles is highly desirable in mechanistic and kinetic studies and since basicities often cannot be used for their predictions, other empirical criteria have been suggested to achieve this end. For SN2 reactions Swain and Scott (1) suggested that the order of relative nucleophilicities of various nucleophiies toward the substrate CH3Br can he used to predict the relative order of their reactivities toward other substrates. They suggested the correlation equation: log (klko) = sn
(6)
where ko is a rate constant for reaction with H20, k is the corresponding rate constant for reaction with any other nucleophile, s is a substrate constant which measures the discrimination of the substrate among various nucleophiles, and n is the nucleophilic constant and is characteristic of the nucleophile only. By definition n = 0.00 for HzO. Methyl bromide was chosen as a standard substrate and s defined as 1.00 for it. Thus when CH3Br is the substrate the correlation is reduced to: log (k/ka) = n
The ratio log (k/lco), for the reaction of N,-, OH-, I-, S20s2-, and aniline with CHaBr at 25°C and in aqueous medium, gave the values of n for these nucleophiles. These values of n were plotted against the experimentally determined ratio log (k/ko) for another H H H I l l substrate (H-C-C-C-CI, epichlorohydrin). The
\/
I
slope of the plot defined the substrate constant s for epichlorohydrin. Then, by using epichlorohydrin as a secondary standard, the value of n for AcO- was determined. Similarly values of n for C1-, Br-, 90
/
Journal of Chemical Educotion
and SCN- were obtained by using glycidol as a secondary standard and the values of n for the picrate anion, So,'-, C6HaN,HCOa-, HP0k2-, (NHa)&S, HS-, SOa2-, and HPSOaa- were determined by using the mustard cation substrate as a secondary standard. The n values are reproduced in Table 1. Table 1.
n Values Determined for Various Nucleophiles
Nucleophile (N) Hz0 AeOC1FBrNa HOC.HrNH% SCN-
n
Nuclwphile
n
0.00 2.72 3.04 2.0 3.89 4.00 4.20 4.49 4.77 5.04 1.9 2.5
I-
picrate anion Sol2-
" J. HINE,2nd ed., p. 161
The applicability of the empirical eqn. (6) was tested by correlating the relative rates of various nucleophiles in 47 reactions involving nine different substrates, in essentially aqueous media, to the order of reactivity of different nucleophilic reagents. This order, revealed by the relative reactivities toward the standard substrate CH3Br, was found to remain remarkably constant for other substrates. The substrate sensitivity to variation in nucleophilicity varied over a wide range as shown by their s values (Table 2). -
Table 2.
Constants for Various Substrates
Substrate 1. Ethyltosylate 2. +CHnCI 3. Epiohlombydrin 4. Glycidol 5. M u s t d cation 6. CBBr 7. B-Pmpiolactane 8. +COCI 9. Benzene sulfonyl chloride
Substrate eonstmt
..
(8)
0.66 0.87 0.93 1.00 0.95 1.00 0.77 1.43 1.25
It must he pointed out that the nine substrates discussed by Swain and Scott can be classified into four groups; (1) substrates whose electrophilic center is a tetrahedral carbon (Table 2, Nos. 1-6); (2) those in which the reaction center is an sp2 carbon (No. 8); (3) those involved in attack on an atom other than carbon, namely sulfur (No. 9); and (4) those in which the attack might be on sp3 and/or sp2 carbon (No. 7). It is noteworthy that the six substrates (No. 1-6) for which there was enough experimental data available to allow a test of the correlation and which indeed obeyed the correlation well were those whose electrophilic site was an spa carbon with minor variation in their steric environment. Of the two substrates whose reaction center was an spa carbon (a carbonyl carbon), one gave a value for log ( ~ o H - / ~ H . owhich ) was much larger than that predicted by the n value of OH-; and for the other, CeHsCOCI, the number of nucleophiles studied was so small and their nature
such that any conclusions based on the data would at best he questionable. The data for the sulfur substrate was again too meager to allow any convincing correlation. Thus, one of the most serious limitations of the Swain and Scott correlation is that its applicability was not tested for reactions involving substrates of really diverse nature. In the one example where there was a major change in the reaction type, in which a displacement on hydrogen was involved (mutarotation of glucose, enolisation of acetone), the deviations were found to be very serious. It was suggested that a new n~ scale based on one of these reactions be set up and applied only to displacements on hydrogen [when the rate of mutarota tion of glucose is taken as the standard, n~ is 2.45 (vs. n = 2.72) for Ac0- and 7.80 (vs. n = 4.20) for OH-]. I n other words, whenever the electrophilic atom in the substrate is changed, a new set of n values has to he determined, i.e., for displacements on P, 0, S, and aromatic carbon (CAr), for example, new np, no, ns, and n c ~ values r have to be set up. For the experimentalist it is a formidable task to determine the rate of reaction of each nucleophile every time the nature of the substrate is changed. Pt(II) A s Reference Substrate
Recently a new set of reactivity constants, np,, has been reported by selecting trans-[Pt(Py)~Clzl as a standard substrate (11). The procedure is essentially that of Swain and Scott (1) except that a different reference substrate is used. The new constants, npt, are defined by the equation: log
(kylk,)~= npt
where k , is a first-order rate constant for the solvolysis of t r a n ~ - [ P t ( P y ) ~ Cin l ~ ]methanol at 30°C and k y is the corresponding second-order rate constant for reaction with the nucleophile Y. The npt values of the 18 nucleophiles which were studied are reproduced in Table 3. Table 3.
Nucleophile
npt Values of Different Nucleophiles npt
Nucleophile
n ~ t
H20 C.H,N
c1-
NHs BrNIOHNo%SCN-
The rates of several other Pt(I1) complexes were then correlated by the equation: where s is a substrate constant which measures the sensitivity of the substrate to variations in nucleophilicity. By definition s = 1.00 for the standard substrate. The s values for several Pt(I1) complexes whose rates were investigated are reproduced in Table 4. The s values of Table 4, which have a reasonable s ~ r e a d .show how chanees in the nature of leavine group and the inert lig&ds change the selectivity 07
Table 4.
Nucleophiiic Discrimination Parameters, s, with Various Pt(ll) Complexes
platinum complexes towards a series of nueleophiies. Since Pt(II), the electrophilic atom in the standard substrate, is highly polarizable (soft), the npb values of Table 3 should be useful in predicting the orders of nucleophilic reactivities toward other complexes whose electrophilic centers are also highly polarizable. Edwards Equations
The limitations of the Swain and Scott correlation were partially eliminated in the Edwards equations. One of Edwards' correlations (12) is based on the assumption that the reactivity of a nucleophile in a displacement reaction is governed by a linear combination of the factors which govern its ability to be oxidized (electrode potential) and its thermodynamic affinity for a proton (basicity). This correlation is represented by log (klko) = aE.
+ BH
(7)
where ko is a rate constant for H 2 0 acting as a nucleophile, k is the corresponding rate constant for any other nucleophile, and ru and are substrate constants which measure the sensitivity of the substrate to changes in E n and H respectively. p y definition H = pK. 1.74, where K, is the ionization constant of the conjugate acid of the nucleophile in water at 25°C and 1.74 is a correction term for the pK. of Haof. The term E , is the standard electrode potential of the reagent X- in the equilibrium reaction,
+
2X-
s
X2
+ 2e-
(8)
relative to that of a similar equilibrium for water: 2H10 H402++ 2-;E ' = -2.60
(9)
E , is then defined by: En = Eo + 2.60 (10) Thus both the parameters, H and En,are characteristic of the nucleophile and are defined in terms of data independent of those to which eqn. (7) is applied; the substrate constants a and p are chosen to give the best agreement with the observed rate data. Although, in principle, the nucleophilic reactivity could be correlated with a linear combmation of any two model processes, the choice of the two processes used in eqn. (7) is well considered. The fact that the nucleophile is formally oxidized in a displacement reaction justifies the choice of the oxidation half cell (eqn. (8)) as one of the measures of nucleophiiicity, while the choice of basicity (thermodynamic affinity for the electrophilic proton) is understandable on the grounds that displacement reactions are generalized acid-ba6e reactions. The main advantage of the double-scale correlation (eqn. (7)) isthat the nucleophilic Volume 44, Number 2, February 1967
/
91
Table 5.
Fundamental Constantsa for Use in Edwards Equations'
Br (NHnhCS CNCNSCICHzCOO-SCHGOOCIHSSO~SH~NCHICH~NHI S--CHrCH20H (CH,O),POS (CHdnNOH CHa(NH),CH3 (C,H.0)9POS Pyridine CaH& 9-NHz (C,H,),N pCHs-+SO*s6-N(CH& c1Re-
a Dsta for Table 5 was oolleated jointly by this writer and Mrs. Alda 0. Kirsis. b The symbols a t the top of the ooiumns are defined as follows: K O = oxidation potential for oxidative dimerization of the nualeophile, E. = Eo 2.60, p K n = -log K., where K, is the ianiastion eonatant for the oonjupate acid of the nuoleophils, H pK. 1.74, R = molar refraction of the nuoleophiie, p =
log
(R/Rad. Valllea in parentheses nre rough estimstes.
reactivity is correlated with two properties of the nucleophile and that the relative contributions of these two properties to the nucleophilic reactivity may vary from one type of substrate to another; allowance is, thus, made for the observed variation in the nucleophilic order with varying substrates. The fact that Edwards observed a linear relationship between the n values of Swain and Scott and the electrode potentials of six nucleophiles suggests that in displacements on tetrahedral carbon the contribution of the term H is negligible. Although the Edwards equation introduces more parameters than did the Swain and Scott correlation, in practice its application is easier. Once the two suhstrate constants a and fi have been determined from rate data, the rate of any number of nucleophiles for which E. and H are known can be calculated. I n the Swain and Scott correlation it would he necessary to determine a new n value for each nucleophile whenever the nature of the substrate is changed. One of the limitationsof eqn. (7),however,isthat many pertinent Ea and pK, values are not known. I n addition, in several cases the substrate constant 0 was found to have a negative value, suggesting that in these cases the factors which enhance the basicity of a nucleophile somehow reduce its nucleophilic reactivity. Since such a suggestion for obvious reasons is not acceptable, Edwards assumed that there was included a significant contribution of basicity in the E, values, or in other words the contribution of the basicity factor was not separated so as to appear in only the H term. 92
/
Journal of Chemical Education
-
+
+
The above difficulty was removed in a later correlation (13). I t was hypothesized that the ability of a nucleophile to be oxidized, or its E. value, is dependent on its polarizability and on its basicity to a proton as expressed: E,
=
aP
+
+ bH
(11)
where H is again = pK, 1.74; P, a measure of the polarizahility of the nucleophile relative to that of water, is by definition P-- log (RJRH,~)with R standing for molar refractivity a t infinite wavelength; and a and b are constants whose values are 3.60 and 0.0624 respectively. Values of all the parameters for various nucleophiles are given in Table 5. By substituting eqn. (11) into eqn. (7),a new douhlescale equation was derived log ( k / k o ) = AP + BH (12) where A (= 3.60a) and B (= 0.0624 a 3.60fi) are substrate constants and other symbols have the same significance as before. The fact that E, values of a number of nucleophies (F-, H20, C1-, Br-, I-, OH- and S2-) calculated by using eqn. (11) are in good agreement with the corresponding obsewed values based on electrode potential data, and the fact that the substrate basicity constant B of eqn. (12) is positive in all cases supports the view that the E, term contains some contribution of basicity and that in eqn. (12) the basicity factor is separated so as to appear in only the H term. I n a recent discussion of factors determining nucleophilic reactivity, Edwards and Pearson (8) have illus-
+
trated with many examples how two properties (presumably basicity and polarizability) of a nucleophile exert varying weights with varying substrates in determining the relative rates of displacement reactions. They have pointed out that for a reaction of the type N+SX
-
NS+X
(13)
basicity of N to proton will play an important role in determining the reaction rate if in the transition state S resembles a proton, i.e., the basicity will become an increasingly important factor in determining the rate of substitution as the positive charge on the electrophilic atom in the substrate increases. I n terms of Edwards' doubloscale correlation the substrate basicity constant B in eqn. (12) will increase as the charge on the substrate increases. The other property, the polarizability of N, can be of significance in lowering the energy of an activated complex to varying degrees depending on the nature of the substrate. Nucleophiles which are highly polariazble have available empty orbitals of relatively low energy. These empty orbitals can be used to accommodate some of the electrons of the molecule N in the transition state. I n addition, these empty orbitals can be used to hold some of the electrons on the substrate S. The net result is a considerable reduction in Pauli repulsion between the non-bonded electrons on N and S. Thus, according to Edwards and Pearson, although polarizability always produces some lowering in the energy of the activated complex because of the flexibility it imparts to the system, it is particularly beneficial for displacements on substrates which have many electrons on the outer orbitals, particularly if these orbitals project well out from the atom S and obstruct the close approach of N. Edwards and Pearson (8) and Bunnett (S), by consideration of the available rate data (which is limited in many cases), have pointed out that the basicity of the nucleophile is the dominating factor in determining rates of substitution on the substrates whose electro~ h i l i catoms are H, carbony1 carbon, trigonal boron,
carbon, bivalent oxygen, Pt(II), and halogen atoms. For displacements on bivalent sulfur and aromatic carbon both basicity and polarizability of the nucleophile govern the rate of reaction. It must be pointed out that these generalizations are subject to exceptions and that not all of them are based on comprehensive studies of the systems involved. Ambident Ions
Certain nucleophilic reagents have two unlike nucleophilic sites, either (but not both simultaneously) of which may attack an electrophilic center. Such reagents are called "ambident ions" (14) and are exemplified by ions such as
and the anion of malonic ester. I n their displacement reactions the more basic end may react preferentially with a substrate whose electrophilic atom acquires a significant positive charge in the transition state (resembles the proton), while the more polarizable end
would react with a substrate whose electrophilic atom has many electrons in the outer orbitals. I n terms of the double-scale eqn. (124, if the substrate basicity constant B is large, the basic end of the ambident nucleophile would attack to a greater extent; and if the snbstrate polarizabiiity constant A is large, the attack by the more polarizable end would be favored. Alpha Effect
It was mentioned earlier that N-phenylhydroxylamine exhibits greater nucleophilic reactivity than does aniline toward peroxyacetic acid where displacement on the outer peroxidic oxygen is involved. Phenylhydroxylamine is a weaker base than aniline (8) and there is no reason to believe that the former reagent possesses abnormally high polarizability. Reagents like hydroxylamine, hydrazine, hydroxamic acids, N-hydroxypthalimide, isonitrosoacetone, the anions of hydrogen peroxide and substituted peroxides, hypochlorite ion, and anions of oximes behave similarly, i.e., they show greater nucleophilic reactivity than what would be warranted by their basicity and polarizability. A common feature of these exceptionally reactive nucleophiles is that they carry at least one unshared pair of electrons on an atom adjacent to the nucleophilic atom (a-atom). Edwards and Pearson (8) have ascribed the greater reactivity of such nucleophiles to stabilization of the activated complex by the lone pair of electrons on the a-atom and have designated the rate enhancing effectas the a-effect. They have suggested that in a displacement reaction a pair of electrons tend to leave the nucleophilic atom and go toward the electrophilic substrate creating a partial positive charge on the nucleophilic atom in the activated complex. If, then, there is a pair of electrons available on the adjacent atom it will stabilize the positive charge on the nucleophilic atom. The stabilization is similar to that observed in the ionization of a-halo ethers, i.e. R-6-CH-ci + R-O-CH~+ + c1-
t
Ibne-Rasa and Edwards (8)have discussed a-effectas arising out of ground state destabilization. The repulsions between the electrons on the nucleophilic atom and those on the a-atom raise the energy of the ground state, while the repulsions are not equally serious in the transition state where the nucleophilic atom is sort of denuded of its electrons. Whatever the explanation, the fact remains that in most cases an electron pair on the atom, a to the nucleophilic atom, enhances the reactivity of the nucleophile. I n summary it may be stated that for correlations of rate data in hydroxylic media the double-scale equations of Edwards give excellent results for displacements on most of the substrates. The n values of Swain and Scott are good only for displacement on tetrahedral carbon, again in essentially hydroxylic media. The rates of nucleophiles which are subject to the ar-effect do not follow even the polarizability basicity scale of Edwards in majority of the cases. Solvation
It has been pointed out by Parker (4) that protic solvents (hydrogen donors like H20, CH30H, and formam'ide) solvate anions by ion-dipole interactions and by Volume 44, Number 2, February 1967
/
93
strong hydrogen bonding which is greatest for small and densely charged anions (low polarizability). Thus solvation in protic solvents decreases strongly in the series OH-, F- >> Cl- > Br- > Na- > I-> SCN- > picrate. On the other hand, in dipolar aprotic solvents (solvents like DMF, DMA, DMSO, MeaCO, CH3CN, @NO2,and sulpholane which contain no hydrogen-bondable hydrogen and whose dielectric constant I- > SCN- > N3- > Br- > C1- > F-, the order in dipolar aprotic solvents may be reversed. Since i t is recognized that salvation is related to polarizability and that solvation is one of the factors which influence basicity, the solvation effect is (implicitly) taken into account in the Edwards' equations (12, 13). This was &st pointed out explicitly by Gould (16). By a discussion of the influence of solva tion on electrode potentials (which constitute one of the scales of reactivity), the importance of solvation in d e termining the nucleophilic orders was demonstrated. Solvation as a dominant factor has also recently been recognized by Hudson (6). According to him, the order of nucleophilic reactivity of a series of nucleophiles toward a single substrate is determined by (a) the energy of desolvation of the nucleophile ( ~ A H Nwhere ) ar is the fraction of desolvation a t the transition state; (b) the energy required to remove one electron from the nucleophile (BEN),where ENis the electron d n i t y of the nucleophile and j3 the fraction of electron removal; and (c) the enerev eained bv formation of the new bond betwkin the n;il&phiie &d the electrophilic center ( ^ / D N - ~where ) 7 i8 the fraction of bond formation a t the transition state. After several assumptions (e.g., assume rr = j3, etc.) the Hudson treatment is reduced to the equation: E = ~(AHN 4- EN - @.DO-N) calstant It has been pointed out by Hudson (6) that this equa, tion is similar in form to the empirical equation proposed by Edwards with one parameter (AHN EN) characterof the nncleophile and One a function *O Of the electrophilic center, with the advantage that the Hudson treatment also gives information on the extent of bond formation in the transition state.
+
+
Soh and Hard Acids and Bases
More recently Pearson (16) has put forward the concept of soft and hard acids and bases (SHAB). Bases (electron donors) whose donor atom is of high polar94
/
Journal of Chemical Education
izability, low electronegativity, easily oxidized, and a e sociated with empty low-lying orbitals are said to be soft. Those which have the opposite properties are said to be hard. Soft acids hare low positive charge, large size, and filled outer orbitals. Hard acids have the opposite properties. According to the concept of SHAB, a complex formed by a soft acid and a soft base is more stable than that formed by a soft acid and a hard base. Similarly a hard acid-hard base complex is more sbble than a hard acid-soft base complex. Among other things this concept can be helpful in understanding nucleophilic displacements which are generalized acid-base reactions. Thus in the reaction:
+ SX + solvent
-
CYS-X-lvent] & Y S X--solvent suppose the acid site (electrophilic center) of the substrate SX is soft. The displacement will occur with particular facility when Y is also soft but X is hard and the solvent is hard. This combiination would ensure strong interaction between Y and S, weak interaction between S and X, strong interaction between X and solvent, and weak interaction between Y and solvent. The cumulative effect of d l these factors would lead to high rate of reaction. It is interesting to note how this treatment emphasizes the role of both the inherent softness of bases (polarizability of nucleophiles) and the influence of salvation. As previously pointed out these two factors are interrelated and neither of them can be ignored. The concept of SHAB disregards the subtle diierence between nucleophilicity (kinetic behavior) and basicity (thermodynamic behavior) with which the organic chemists have become so familiar. Furthermore the concept is presently useful only for qualitative predictions. It may in future be applied in a quantitative manner if some parameter, such as the reactivity constant n p t of Table 3, is available as a quantitative measure of "softness." Y
+
Likratura Cilad (I) SWAIN,C. G., AND SCOTT, C. B.,J. Am. chm. SOC.,75,141 (1953). (2) EDWARDS, J. O., AND P E ~ O N R. ,G., J. Am. Chem. Soc., 84.16 (1962). (3) BUNNETT, J. F., Ann. Reu. Phys. Chem., (H. EYRIN~, Editor) Ann. Reus., Pdo Alto, 1963, pp. 211-290. (4) PARKER, A. J., Chem. Soc., Quart. Rwa., 16, 163 (1962). (5) HUDSON, R. F.,Chimia, 16, 173 (1962). (6) INGOW, C. K., "Structure and Mechanism in Organic Chemiatm." ". Cornell Univ. Press. Ithaca. N.Y.. 1953.. .o. 200. (7) SMITH, G.F.,J. C h m . Soc., 521 (1943). (8) IBNE-RAEA, K. M., AND EDWARDS, J. O., J. Am. Chem Soc., 84, 763 (1962). (9) PBA&SON, R. G.,AND EDGINGTON, D. N., J. Am. Chem. Sac, 84,4607 (1962). (10) JENCXS, W.P., AND CARXIUOLO, J., J. Am. Chem. Soc., 82, 1778 (1960). (11) BELLUCO, u.,CATPALINI, L.,BASOM,F., PEILRSON. R. G., AND Tmco, A., J. Am. Chem. Soc., 87, 241 (1965). (12) EDWARDS, J. O., J. Am. C h m . Soc., 76, 1540 (1954). (13) Enwms, J. O., J. Am. C h m . Soc., 78, 1819 (1956). (14) KORNBLUM, N., SUILEY,R. A,, BLACKPOOD, R. K., AND IFFLAND, D. C., J. Am. Chem. Soc., 77,6269 (1955). (15) Gourn, E, S,, and structure in Organic Chemistry," HoltDryden, New York, 1959,p. 260. (16) PEAESON, R. G., J. Am. Chem. Soc., 85, 3533 (1963).
