Bernard E. Hoogenboom Gustavus Adolphus College St. Peter, Minnesota
Homolytic, CatiOnOtrOpkf and Anionotropic Reactions A mechanistic approach to organic chemistry
It is useful for the undergraduate student to study organic chemistry as a series of bond breaking and bond makmg processes. Bond breaking processes may be categorized as those which involve (1) homolytic fission of an electron pair bond, resulting in the formation of neutral free radicals, and (2) heterolytic fission of the electron pair bond leading to ion pairs. Bond making, therefore, may he thought of as (1) a pairing of electrons, as in radical reactions, or (2) the donation and acceptance of an electron pair. Bond making may precede, follow, or occur simultaneously with, bond breaking. One of the goals of the mechanistic approach to teaching organic chemistry is to develop in the student the ability to predict the course of a reaction on the basis of the molecular and electronic structures of the organic substrate. By a consideration of the relative electronegativities of six or seven elements, it should be possible to select the reactive point(s) in any organic compound where it is vulnerable to attack by electronrich particles (bases or uucleophiies) or by electroudeficient particles (acids or electrophiles). The bond making aspect of the ion-ion, ion-dipole, and dipoledipole interactions characteristic of most organic reactions involves the donation and acceptance of an electrou pair; in other words, the polar or heterolytic reactions of organic compounds involve simple acid-base interactions. Lacking an understanding of electronic structures and of electronic interactions within and between particles or molecules, students usually resort to memorizing individual reactions or (at best) general reactions of individual classes of compounds. They are frequently led to erroneous predictions of chemical reactivity without even considering the correct and most logical conclusion. The fault for such careless errors, however, must lie as much with the instructor as with his students. Students may be taught to select the reactive points in stmctures on the basis of the relative stabilities of bonds with respect to homolysis and heterolysis. This approach is especially useful for predicting free radical or homolytic reactions because hond dissociation energies for many different bonds are known and have been tabulated (1). It would seem to be more difficult to predict heterolytic reactions in the same way because relatively few heterolytic bond dissociation energies are known (f). In a qualitative way, however, differences in ease of hond homolysis and bond heterolysis may be predicted
for any organic substrate which can be recognized as having an X=Y-Z-A generalized structure. I t is useful for the student to recall the rule, originally called the Schmidt double bond rule (5), that in such a system bond Y-Z is strong and bond Z-A is weak. This rule may he applied quite extensively to both homolytic and heterolytic reactions because many of the complex and polar functions encountered in the study of organic chemistry may be identified with the X=Y-&A general system. In the X=Y-%--A general system, the atom or group of atoms A can he considered to be "active" and will show a tendency to dissociate as a radical, A , , an anion, A?, or a cation, As. The manner by which atom A dissociates depends on the nature of atoms X,Y,Z and A and on the conditions of the reaction. A driving force for the dissociation of atom A is the stabilization of the remaining X=Y-Z radical, cation, or anion by solvation and/or charge or electron delocalization.
Some form of stabilization of the dissociated atom A may provide added driving force for the reaction. Radical Reactions
Bond dissociation energies ( 1 ) illustrate the applics, tion of the X=Y-Z-A rule in predicting the course Table 1 .
C-H H-H CHs-H
Bond Dissociation Energies, kcal/mole ( 1 ) 103 102
CHdHCHpH C6HsCHrH
77.0-80.0 77.543.0
Presented in part before the Division of Chemicsl Education at the 147th Meeting of the ACS, Philadelphia, April, 1964. Volume 41, Number 12, December
1964
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639
Table 2.
C-C
Bond Dissociation Energies, kcal/mole ( I )
CHs=CHCHx-CHX
of radical reactions. The dissociation energies of C-H and C-C bonds (Tables 1 and 2) in benzyl and allyl positions, which correspond to bond %A in the general system, are decidedly lower than those for the saturated and vinyl systems. The easier free radical abstraction or replacement of hydrogen atoms in an allyl or benzyl position is thus expected and, indeed, is well known (4). In the light or peroxide induced chlorination of toluene, the benzyl free radical is more highly stabilized, or is of lower energy, than any other possible free radical and is therefore most favorably formed. Stabilization of the benzyl free radical is by delocalization of the single electron.
61.5
a stable free radical; N1,N'-diphenyl-N-picryl-hydr* sine (DPPH) apparently exists only in the radical form (lc). Peroxides and azo compounds capable of homolytic dissociation to form stabiiized radicals of the type X=Y-Z show low bond dissociation energies (la), low decomposition temperatures ((?a), low decomposition activation energies (@I), and short half lives (4b) (Tables 3 and 4). Table 3.
RO-OR
The Schmidt rule was originally used to predict the coune of the pyrolytic dissociation of naturally occurring materials, such as limonene (3). CHz I
In accordance with the rule, alpha hydrogen atoms in ketones, acids, and other carbonyl containing compounds are readily abstracted. Picrylhydrazine forms
2 RO
.
BDE ( 1 ) Decomp. temp., (kcal/mole) 'C (6aj HO4H (CHS)~CO-OH
In the auto-oxidation of allyl or benzyl compounds such as cumene, tetralin, and cyclohexene (0, initiation of the free radical reaction leads most favorably to the formation of the allyl or benzyl free radical rather than to any other secondary or vinyl radical.
-
Decomposition of Peroxides
52
..
. .. 140-180
- Half life at 80QC= 6700 hr (4b). *Half Life at 80°C = 5.87 hr (4bj.
In allylic brominations, N-bromosuccinimide may function as a source of molecular bromine (7a, b, c), although fission of the N-Br bond in NBS probably does not occur as easily as might be anticipated on the basis of the X=Y-Z-A rule1 (74 e). Cationotropic Reactions
The heterolysis of bond %--A falls in the realm of the well established concepts of cationotropy (8a) and anionotropy (Xb). In cationotropic reactions of the system, atom A dissociates as a general X=Y-Z-A cation. Prototropy (8c) is of course a special case of cationotropy which involves the dissociation of atom A as a proton. The unexpected high thermal stability of the N-N bond in N,N'-bisuecinimidyl (7d) and N,N'-biphthalimidyl ( r e ) suggests that the N-Br bond in NBS may &o be stronger than expected and that the succinimidyl radical is not capable of a high degree of stabilization.
Table 4.
Decomposition of Azo Compounds
CHaN=NCHa (CH,)*CHN=NCH(CHD)~
Decamp. temp., "C (8a)
E. ( B b ) (kcal/ mole)
300 250
50 41
=Halflife at 8 0 T = 1.21 hr (4b).
By recognizing a portion of a molecule as an X=YZ-A system, a student is able to make valid predictions regarding the cationotropic reactivity of the atom or atoms in the molecule corresponding to atom A in
-
Table 5.
X=Y--Z-H O=C-0-H I
L
-
the general case. For example, he can predict that a proton should dissociate from a carboxyl group, from atoms alpha to carbonyl, cyano, nitro, and sulfonyl groups, from enols and phenols, amides, imides, oximes, C-nitroso compounds, N-nitroso compounds, and diazoic acids (Table 5). Systems in which atom A can be removed as a proton are capable of ketoenol tautomerism. The tautomeric forms themselves may be recognized as X=Y-%--A systems and are, therefore, sources of protons. Application of the rule also suggests that hydrogen on nitrogen in aniline and diphenyl amine should be replaceable by alkali metals if not by strong Lewis bases. Moreover, bases should quite easily remove a proton from systems such as cyclopentadiene, indene, fluorene, and cycloheptatriene (9) (Table 5). Removal of an ally1hydrogen as a proton may be predicted as the first step in the basecatalyzed isomerization of 3-phenylpropene to 1phenylpropene. The reactivity of the alpha hydrogens in sulfoxides
-
Prototropic Dissociation of Acids of the Type X=Y-Z-H
X=Y-Z:e O = C O :.a I
X-Y=Z
L
H-X-Y=Z
I w g a n i c acids:
O=CO--H
AH b N U H O=N--O-H
I
0
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641
and sulfones and the acidity of sulfonic acids, sulfonamides and snlfonimides may also be predicted by the rule if non-octet structures for sulfur (10) are assumed. I n the realm of inorganic chemistry, the strongly acidic nature of some of the common ternary acids may be similarly understood. The acidity or the ease of dissociation of a proton from an 0-H bond in a carboxylic acid does not appear to be related in any direct way to the homolytic bond dissociation energy of a carboxylic acid 0-H bond. The 0-H bond dissociation energy for acids (102 and 111.5 kcal/mole for benzoic and acetic acids, respectively) (11) are higher than most C-H bond dissociation energiw (Table 1). For this reason, an active radical more readily abstracts a hydrogen atom from a C-H bond rather than from the 0-H bond in a carboxylic acid. The 0-H bond dissociation energies for acids are even higher than those of most alcohols (100-117.5 kcallmole) (la, e). I n aqueous solutions, however, carboxylic acids lose a proton more readily than do alcohols. The acidic properties of carboxylic acids are thus thought to be due primarily to the solvation energy of the carboxylate ion and to the high electron affinity of the carboxylate radical, RCOO. (11), which, in turn, depends on the extent of charge dispersal in the carboxylate anion. The extent of stabilization of the anion by both solvation and charge delocalization thus determines the acidity of the source of a dissociable proton, the conjugate acid. The relative acidic properties of carboxylic acids, phenols, amides, and imides are well known. Morton (Qa), McEwen (9b), and, more recently, Dauben and co-workers (Qc) have determined the pKa values and relative acidities of a number of hydrocarbons. It is obvious from the relative acidities of carboxylic acids, phenols, amides, imides, ketones, and hydrocarbons that the acidity of a source of a proton is dependent in part on the electronegativity of the atom to which the dissociable proton is attached. Thus the relative ease of protolytic dissociation is as follows: -0-H
I I > N-H > -C-H I I
I n an analogous way, the ease of dissociation of a positive halogen atom (18a) depends not only on the stabilization by salvation and charge dispersal of the resnlting anion, but also on the electronegativity of the atom to which the halogen is attached. Thus the relative ease of dissociation of a chloronium ion, Cle, is:
Table 6. C-Halogen R-A R H CH1 CHsCHn CsHa CHFCHCH~ C.HCH, a
Homolytic Bond Dissociation Energies, kcallmole ( 7 )
-
R.
+ A . (halogen)
F 134 107 (106) (145)
... ...
( ) denotes estimated figure. Vinyl chloride, CHFCH-CI,
642
C1 102
'::'" 86& GO 68
Br
I
86.5
70.5 53 51 57 36 39
71 46 51
104 kcal/mole.
/ Journol of Chemical Education
These generalizations regarding the electronegativity of atoms bearing the dissociating atom A are applicable to virtually all systems, whether or not they are of the X=Y-Z-A type. Other reactions which lead to or involve stabilized anions of the X=Y-Z:e type include the decarboxylation of malonic acids and betaketoacids (18b), and the base-catalyzed cleavage of beta-ketoesters and beta-diketones (18~). Anionotropic Reactions Heterolytic cleavage of bond Z-A to form the anion A 9 and the cation X=Y-Z@ is limited practically to cases in which atoms X and Z are carbon because of the inability of a more electronegative element, such as oxygen, to accommodate a positive charge. The lability of bond &A in anionotropic reactions of the X=Y-Z-A general system is well illustrated by the ease of formation of allyl and benzyl carbonium ions as intermediates in the solvolysis reactions of tosylates and halides (IS) and the dissociation of allyl and benzyl oxooium ions (14).
- +-
CaH&HzBr Bre CHFCH-CH20H2"
HOH
C6HSCH,*+CaH5CHrOH CH2=CH-CH,' OHz
+
Tropylium bromide exists as a completely dissociated water-soluble salt, in which the tropylium cation is highly stabilized by salvation and by delocalization of the positive charge (15).
Although the parallel between the ease of anionotropic dissociation and homolytic bond dissociation energies of alkyl, allyl, and benzyl halides (Table 6) (1) is obvious, the gas-phase homolytic bond dissociation energies do not truly reflect the energy requirement for the separation of two particles of opposite charge. The relative ease of formation of alkyl, allyl and benzyl carbonium ions is more adequately shown by the gasphase heterolytic bond dissociation energies of various alkyl hydrides (hydrocarbons), halides, and alcohols, and by the ionization potentials of the corresponding free radicals (Table 7) (8). The isomerization or allylic rearrangement of allyl alcohols in the presence of acids, and of allyl halides in thc prw:r~reof polar solvents, mnst also involve anionotropic disnocirrtio~~ of S=-Y-Z-.\ systems @a, 16).
The bimolecular displacement reaction (SN2) may be considered to be an anionotropic heterolytic reaction in which atom A in a general case is displaced as A:e by another nucleophilic atom or group of atoms, B:e. The ease of bimolecular displacement of atom A in X=Y-Z-A systems as the anion, A:e, is shown in the relative rates of reaction of a series of halides under the conditions of SN2reaction (Table 8) (17). The Claisen, or phenyl allyl ether, rearrangement may involve either heterolysis or homolysis (18) of an allyl 0-C bond, but is consistent with the pattern of other allyl rearrangements.
Table 7.
Gas Phase Heterolytic Bond Dissociation Energies, kcal/molea (2)
R-A-R'+A:e
In the case of propene or toluene, a hyperconjugative effect may give the vinyl C-C bond added strength through partial double bond character. CHFCH-CH-H,
( C HLC. ~
171
The heterolytic bond dissociation energies were calculated from the hornolytic bond dissociation energlea, BDE, of molecules R-A. the ionization ootentiala. I. of rrtdicals R.. and the electron aflinides, E.A., of radicals A . by &herelation: a
6 This data suggests that tertiary earbonium ions are more readily formed than ally1 or benayl earbonium ions m d that the byperconjugative stabilization of s. tertiary butyl carbonium jon mav be more effective than the stabilization by coniugatlve
ease'af formation and eGtent
of stabilization by charge dispersal.
The extra strength of hond Y-Z in the X=Y-%--A system is indicated by the higher homolytic bond dissociation energies of vinyl type compounds (Tables 1, 2, and 6). The limited data available for direct comparison (Tables 6 and 7) suggest that the heterolytic hond dissociation energies of the same vinyl type compounds should he even higher. One might rationalize the difficulty of breaking a vinyl bond, either homolytically or heterolytically, on the basis of the lack of appreciable stabilization of the resulting vinyl radical, anion, or cation. Moreover the interaction of an electron pair on halogen, for example, with an adjacent pi bond system, which imparts to the C-halogen bond some double bond character, makes that hond stronger than the normal C-halogen single bond found in methyl or ethyl chloride. Table 8.
Relative Rates of Biomolecular Nucleophilic Displacements of Halidesa (17)
R-A R-A
He
It should thus be obvious to the student that vinyl and aromatic halogen and alkyl groups, enolic, phenolic, and carboxylic acid hydroxyl groups, and other atoms or groups of atoms occupying a vinyl position are not easily removed or replaced under any non-forcing conditions.
Radical ion.pot.
R. -
e:CHrCH=CHs
+ B:*-
R-B
Rel. rate
+ A:e(hdide) R-A
Rel. rate
As A. A. Humffi-ay (19) has indicated, electronic theory and stabilization by charge or electron delocalization can be presented to students in terms of an X= Y-Z generalized system in which atom Z bears an unpaired electron, an electron pair, or a positive charge. Bond X-Y need not be double, nor need it be a localized double bond; it may be a triple bond, as in C=N or G C , or it may be any delocalized system of pi electrons as in the phenyl group. Atoms X and Y may he replaced entirely by a single atom, such as sulfur, hearing an electron pair and capable of expanding its valence shell.% In the general case of R-&z-A, in which sulfur has replaced atoms X and Y, the radical, anion, or cation formed by homolytic or heterolytic dissociation of atom A is capable of stabilization by charge or electron delocalization (10). Alpha-haloethers, R-6-CRZ-X, undergo rapid solvolysis in aquronn dioxnne heesusr tho intrrmrd~atrcilrlm~iuni (oxon~uro)Ion (IWCH,' .-- ROS-C'R.) is caonhle of stabilization by charge-delocalization (I.%). ~ i i p h a t i c ethers, R-&CR2-H, such as diisopropyl ether, suffer rapid homolytic abstraction of alpha hydrogen atoms and in the presence of oxygen form alpha-hydroperoxides (20). As a final case for the Xd-Z-A rule, it can he notred that perhenzoic acid, despite its name, is only weakly acidic (Ki=10-9) (6e) compared to benzoic acid (K,=10-9). Apparently, stabilization in the perbenzoate anion is less effective than in the benzoate ion. Perbenzoic acid does, however, readily release benzoate radicals by dissociation of the 0-0 hond (estimated BDE = 30-50 kcal/mole) (la). The benzoate radical, like the benzoate ion, is capable of stabilization by electron delocalization.
+I
O=CO-O-H X=Y-Z-A
o=Lo-O:~ d
//*
O=h-0. X=Y-Z.
+ He, K, = lo-'
+ .OH, BDE = 3&50 kcal .A
' Moreover, a hydrogen atom is more easily abstracted from an ethyl radical ( . CHZ-CH2H + CH-CH2 H ., B D E -37 kcal/mole) (le,f) than from an ethane molecule (Table
+
a
Compilation of data by author.
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643
There may he exceptions, or even extensions, to the general rule as formulated, but it is of considerable value to students who make use of it for predicting the reactions of most polar functions. For pedagogical purposes it is not necessary to place restrictions on the nature of atoms X, Y, Z, and A. The essential prerequisite for undergraduate students is that they understand thoroughly the basis of the X=Y-Z-A rule and that they be able to recognize the X=Y-Z-A system in compounds with which they are concerned. Apparently atoms X , Y, and Z in the X=Y-Z-A system may he any combination of any elements in Periodic Groups IV, V, and VI. I n actuality, it is observed that X=Y-Z systems are usually comprised of the elements C, 0, N, S,and P. Atom A, when highly electronegative or when attached to an atom Z of low electronegativity, will tend to dissociate as an anion. The resulting cation, X=Y-Za, in which atoms X and Z bear partial positive charges, is capable of the greatest degree of stabilization if both X and Z are of low electronega tivity. When of low electronegativity or when attached to an atom Z of high electronegativity, atom A is most likely to dissociate as a cation. The resulting anion, X=Y-X:e, is capable of a maximum stabilization by electron or charge delocalization if either X or Z is of high electronegativity. Atom A in the general case may be monovalcnt or higher; it is usually found to be H, C1, Br, I, 0, N,or S. Among the most recent undergraduate organic chemistry text books using the mechanistic approach, only one (6a) makes extensive use of the concept of the X=Y-Z-A system presented in this paper. I n that text, some attention is given to the premise that in such systems, bond Z-A is weak3 and that free radicals, anions, and cations having an X=Y-Z stmcture are capable of stabilization by electron or charge delocalization. Unfortunately, the unusual bond strength of bond Y-Z in the general case is not related in that text to reactions of actual chemical systems. It appears that the concept of the X=Y-Z-A generalized system can be used to advantage in presenting a more unified picture of organic chemistry, not only to undergraduate students, hut to graduate students as well. Indeed, it is conceivable that the practicing organic chemist may find it useful. Acknowledgment
The author wishes to acknowledge with appreciation the helpful comments and suggestions of Dr. R. L Hinman during the preparation of this paper. Literature Cited (1) (a) COTTRELL,T . L., "The Strengths of Chemical Bonds," Butterworth, Inc., Washington, D. C., 2nd ed., 1958, Chapter 11. (b) STREITWEISER, A,, "Molecular Orbital Theory for Organic Chemists," John Wiley & Sons, Inc., New York, 1961, p. 393.
"
brief discussion of the activation of atom A in such systems is given in FIESERand FIESER,"Advanced Organic Chemistry," Reinhold Publishing Cow., New York, 1961, pp. 12630.
644 / Journal of Chemical Education
(c) KETELAAR,J. A. A,, "Chemical Constitution," Elsevier Publishing Co., New York, 1958, pp. 205, 7 6
(d) SEWARC, M., Chem. Rev., 47,75 (1950). (e) WALLINQ, C., "Free Radicals in Solution," John Wiley & Sons, Inc., New York, 1957, pp. 48-50. (f) KNOX,B. E., AND PALMER, If. B., Chem. Rev., 61,247 (19R1>. ~ ~ - , ~ L. N., "The Modern Structural Theory of (g) FERGUSON, Organic Chemistry," Prentice-Hall Inc., Englewood Cliffs,New Jersey, 1963, p. 46. (h) Coops, J., Rec. trav. Chim., 72,785 (1954). STREITWEISER, A., "Solvolytic Displacement Reactions," McGraw-Hill Book Co., Inc., New York, 1962, pp. 42. 181. S C ~ I D T , O., Ber., 68B, 60-7 (1935); Z. Elektwehim., 39, QRQ (19331. ( a ) 6~-ERASSI, C., Chem. Rev., 43,271 (1948). (h) DAUBEN, H. J., AND McCoy, L., J. Am. Chem. Soe., 81, 4863 (1959). (a) FRANK,C. E., Chem. Rev., 46,155 (1950). JR.,W. J., J. Org. Chem., 29,391 (1964). (b) FARRISSEY, F. G., "Organic Chemistry," The Mac(a) BORDWELL, Millan Co., New York, 1963, pp. 389, 391. (b) GOULD,E., "Mechanism and Structure in Organic Chemistry," Holt and Company, New York, 1959, pp. 724-725. F. G., 1m. eit., p. 138. (c) BORDWELL, D., J. Am. (a) WALLING,C., REIGER,A. I., and TANNER, Chem. Sac.. 85. 3129 (1963). R.'E., AND M A R T ~ N , J. C., 3. Am. Chem. (b) PEARSON, Soc.. 85. 354 119631. K. M., (c) RUSSEL, G. A.,'DEB&R, c., AND DESMOND, J . Am. Chem. Soc., 85,365 (1963). (d) HEDEYA,E., HINMAN,R. L., AND THEODOROPULOS, S., J. Am. Chem. Soc., 85,3052 (1963). C., . ~ N DNAGLIERI,A. N., J. Am. Chem. (e) WALLING, Soc., 82, 1820 (1960). e Mechanism in Organic INGOLD,C. K., r ' S t r u ~ t u ~and Chemistry," Cornell University Press, Ithaea, New York, 1953, (a) pp. 219, 530-75, (b) pp. 218, 586601, (c) pp. 547-75. (a) MORTON, A. A., Chem. Rev., 35.9 (1944). (b) MCEWEN,W. K., J. Am. Chem. Soe., 58, 1124 (1936). (c) Chem. and Eng. News, Sept. 16, 1963, p. 61. A,, "Sulfu~Bonding," Ronald PRICE,C. C., AND SHIGERU, Press, New York, 1962. JAFFE, L., PROSSEN,E. J., AND SZWARC, M., J. Chem. Phys., 27, 41620 (1957). (a) Ross, S. D., FINKLESTEIX,M., AND PETERSON, R. C.. J. Am. Chem. Soc.. 80.432711958): ,, SCHMIDT E., &CHERL, A,, AND V& KNILLING, W., Ber., 59B, 1876-88 (1926); HOWELL,L. B., AND NOYES, W. A., J.Am. Chem. Soe., 42,991 (1920). (b) Gonm, E., lac. cit., p. 346. ( c ) Goum, E., ibid., p. 337. (s) STREITWEISER, A,, " S ~ l v ~ l y t iDisplacement c Reactions," McGraw-Hill Book Co., Inc., New York, 1962, pp. 44, 75. , lot. eit., (b) STREITWEISER, A,, ibid., p. 103; G O U L ~E., p. 282. STREITWEISER, A., "Molecul~~r Orbital Theory for Organic Chemists," John Wiley & Sons, Inc., New York, 1961, n. 36.5. r~- - - . DOERING,W., AND KNOX,L. H., J. Am. Chem. Sac., 76, 3203 (1954). . . (a) GOULD,E., loc. cit., pp. 286, 343. (h) DEWOLF,R., AND YOUNG,W., Chem. Rev., 56, 784801 (1956). A,, "Solvolytic Displacement Reac(a) STREITWEISER, tions," McGraw-Hill Book Co., Inc., New York, 1962, pp. 13, 28. J. B., J. Am. Chem. Soe., 47,488 (1925). (b) CONANT, INGOLD, C. K., loe. cil., p. 598. A. A,, J. CHEM.EDUC.,30,635-7 (1953). HUMPFRAY, (a) GOULD,E., loc. cit., pp. 715-16. (b) STEERE,N. V., J . CHEM.EDUC..41, A575 (1964). ~
(2) (3)
\----,-
(4) (5) (6)
(7)
.
