Research: Science and Education

Using Acidities To Demonstrate Principles W of Organic Structure and Bonding

Andrew P. Dicks Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada; [email protected]

A recent article in this Journal (1) discusses the proper- Hybridization Effects ties of acidic substances not containing a formal carboxylic acid functionality. The authors elaborate on a number of car- Acidities of , , and are discussed bon-based acids, such as Meldrum’s acid and dimedone. in most introductory organic chemistry textbooks (4). The 3 Other compounds that could be considered in this context pKa of ethyne (acetylene) is well established (25.5 in DMSO ; are (substances containing only hydrogen and ref 5). Acidities of ethane (pKa = 49–62; ref 6) and ethene carbon). Conant and Wheland undertook the first “study of (ethylene, pKa = 42–45; ref 7) are less well known owing to extremely weak acids” in 1932 and by colorimetric methods experimental difficulty in accurately measuring pKa values of were able to arrange 10 hydrocarbons in a scale of increasing such weakly acidic compounds.4 acid strength (2). McEwen (3) extended this work by quan- Hydrocarbon acidity increases as the percentage s char- tifying the acidity of these compounds (and many others) acter in hybrid orbitals of carbon increases; that is, a corre- with respect to the acid dissociation constant of methanol. lation exists between hybridization and acidity as shown in The most acidic hydrocarbon noted by these researchers was Table 1. Walsh (8) has suggested that carbon electronegativ- 1 9-phenylfluorene (Figure 1) with a pKa = 21(3). ity towards hydrogen is greatest for an acetylenic carbon atom. 2 Ϫ The pKa values of many structurally diverse hydrocar- A C H bond in ethyne therefore has a comparatively high bons have been measured during the last 70 years. A striking bond dipole of sign Cδ−ϪHδ+. The ability of an sp hybrid- feature of the collected data is the enormous acidity range ized carbon to attract electrons is related to conjugate base covered. Hydrocarbon acidities encompass an astonishing 50 stabilization. The relative base stability order formed by pro- orders of magnitude (minimum) and thus span the majority ton loss from each hydrocarbon is shown in Figure 2. of known acid behavior. Examination of such wide-ranging The acetylide anion formed by deprotonation of ethyne acidities facilitates a classroom discussion concerning funda- is more stable than corresponding anions derived from ethene mental principles of organic structure and bonding. This re- and ethane. An sp hybrid orbital (present in the acetylide view article highlights the acidity of different types of anion) possesses 50% s character and 50% p character. As hydrocarbons and rationalizes observed trends. Emphasis is an s orbital is lower in energy and closer to the carbon nucleus placed upon undergraduate concepts of hybridization, reso- than a p orbital, the negative charge developed on hydrocar- nance, induction, and . bon deprotonation is stabilized most for the acetylide anion. This effect leads to increased dissociation of ethyne compared to ethene and ethane and thus increased acidity. A sufficiently H Ph strong base such as an amide ion can deprotonate ethyne (Scheme I). The equilibrium constant for this equilibrium is 3.16 × 1010 meaning that ethyne is essentially completely deproto- nated (> 99.9%) under these conditions. This behavior is ex- Figure 1. 9-Phenylfluorene. The most acidic proton is highlighted tended to any terminal (one possessing an acetylenic by a bold H. hydrogen, RϪCϵCϪH). Anions derived from terminal alkynes are useful in constructing carbon chains, as they act as excellent nucleophiles in SN2 reactions (9) (Scheme II). H H An sp3 hybrid orbital (25% s character) cannot stabilize a ؊ ؊ ؊ H CC > CC > H3CC negative charge developed in the resulting anion as effectively H H H and alkanes are observed to be much less acidic than alkynes. A linear relationship between acidities of 10 non- decreasing stability conjugated hydrocarbons and hybrid orbital composition has Figure 2. Relative order of conjugate base stability of two-carbon been reported (10). In this study hybridization parameters hydrocarbons. were calculated by the scaled maximum overlap (SMO) method.5 This approach defines hybrid orbitals in the form spn, where n often represents a noninteger hybridization in- dex exponent (second-order hybridization). A general wave Table 1. pKa and Hybridization of Two-Carbon function for an spn hybrid (n being an integer or not) is given Hydrocarbons by the expression Mnolecule Cparbon Hybridizatio Ka Epthane s 3 49–62 1 1 ψ =+22s n 2 p ()n + 1 − 2 Epthene s 2 42–45 () Epthyne s525. Even for a simple molecule such as ethyne the use of integer

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؉ ؊ ؊ ؉ H CCH NH2 H CC NH3 hybrids to describe covalent bonds has no quantitative basis. acetylide There is no reason to suppose the “best” hybrid orbital to pK = 25.5 pK = 36 a anion a form a CϪH bond in ethyne has an identical s:p ratio as present in the triple bond. According to the SMO method Scheme I. Formation of an acetylide anion. an acetylenic carbon forms a CϪH bond with a hybrid or- bital described as sp1.29, corresponding to 43.6% s character. When hybrid orbitals are idealized (sp, sp2, or sp3; first-or- ؊ der hybridization) the correlation with hydrocarbon acidity ' R CC ؉ R' CH XCHRR C C 2 2 is much poorer (Figure 3). R' = H, 1° alkyl Highly strained possess CϪH bonds con- or alkenyl new CÐC bond taining an unusually high degree of s character. Carbon or- X = Cl, Br, I bital hybridization used for CϪH bonding in cyclopropane 2.36 3 Scheme II. Carbon–carbon bond formation. is calculated as sp rather than sp (11). The hybridization index for an spn hybrid orbital is related to the NMR 13CϪH coupling constant (J13C-H) by (12):

؊؉ 1 1 Li 500 n-BuLi J 13 ()Hz = H C-H n + 1 H H 2 2 Cycloalkanes forming CϪH bonds with hybrid orbitals of 2,7 tricyclo[4.1.0.0. ]- greater than 25% s character (J13C-H > 125 Hz) exhibit en- heptane D2O hanced acidity. The strained tricyclic hydrocarbon 2,7 1 tricyclo[4.1.0.0. ]heptane (Scheme III) should theoretically be more acidic than a saturated such as n-heptane. D Ϫ J13C-H for the C1 H bond has been measured as 200 Hz, H while J13 for the C2ϪH bond is 146 Hz (13). This corre- 2 C-H sponds to a hybrid orbital of composition sp1.50 involved in the C1ϪH bond (40% s character) and a hybrid orbital of 2,7 Scheme III. Acidity of tricyclo[4.1.0.0. ]heptane composition sp2.42 involved in the C2ϪH bond (29% s char- acter). Increased acidity of tricyclo[4.1.0.0.2,7]heptane is veri- fied by salt formation on treatment with n-butyllithium, 50 followed by deuteration on addition of D2O (Scheme III). Streitwieser has noted a correlation between J13C-H and kinetic acidities of cycloalkanes (14). Rates of hydrogen–tri- tium (T) isotopic exchange were measured in N-tritiated cy- 40 clohexylamine catalyzed by cesium cyclohexylamide (Table

a 2). The dominant factor determining acidity is K

p the quantity of s character in the CϪH bond hybrid orbital. ethyne 30 Cycloheptane and cyclooctane are slightly less acidic than second-order cyclohexane (smaller s character). More highly strained rings first-order appear more acidic than cyclohexane (larger J13C-H, greater s character). 20 20 30 40 50 Resonance and Inductive Effects Percent s Character The preceding section highlights factors increasing an- Figure 3. Plot of hybrid orbital % s character versus measured acidity ionic stabilization that promote increased hydrocarbon acid- for first-order hybridization and second-order hybridization (10a). ity. Another stabilizing effect is resonance delocalization of charge. This effect is illustrated by comparing the acidities of cyclohexane (pKa = 52; ref 15) and cyclohexene (pKa = Table 2. Relationship between the Rates of H–T Isotopic 46; ref 16 ). Deprotonation at an allylic position in cyclo- Exchange and 13C–H Coupling Constantsa hexene forms a resonance stabilized anion (Figure 4). For- b He y d r o c a r b o n E x c h a n g e R a t J13C-H /Hz mation of this conjugate base is energetically more favorable 4 than generation of the corresponding anion from cyclohex- C0yclopropane 7.0 x 1 161 ane, hence cyclohexene exhibits greater acidity. C8yclobutane 2413 Similarly, formation of the resonance stabilized benzyl C7yclopentane 58. 12 anion rationalizes the greater acidity of (pKa = 42; C1yclohexane 123, 12 4ref 17) compared to (pKa ≈ 55; ref 18). Toluene is C6ycloheptane 03.7 12 at least 13 orders of magnitude more acidic than methane. C4yclooctane 02.6 12 Four canonical forms can be drawn for the benzyl anion (Fig- aData from ref 14. bThe exchange rate is relative to cyclohexane. ure 5), where the negative charge is delocalized to ortho and

JChemEd.chem.wisc.edu • Vol. 80 No. 11 November 2003 • Journal of Chemical Education 1323 Research: Science and Education para ring positions. A greater degree of charge dispersion in ؊ this anion than the cyclohexenyl anion leads to toluene ap- 4 pearing more acidic than cyclohexene by a factor of 10 . ؊ Implicit in construction of such canonical forms is co- planarity of the ring with an sp2 hybridized carbon, as maxi- mal p orbital overlap will ensue. Charge delocalization lowers Figure 4. Resonance delocalization of charge in the cyclohexenyl the energy of the benzyl anion. A proton is more readily lost allylic anion. from toluene than from methane since no resonance stabili- zation of the methyl anion is feasible. This concept is ex- tended to , Ph2CH2, pKa = 32 (19), and ؊ , Ph3CH, pKa = 30 (19b, 20). CH CH One can construct 7 and 10 canonical forms for the an- 2 2 ions derived from diphenylmethane and triphenylmethane, ؊ respectively. The acidities of these compounds are a function of contributing steric and inductive effects (21, 22), illus- trating caution should be exercised in making simple corre- lations between canonical structures and delocalization energy. It has been concluded that “more than half of the ؊ enhanced acidity of triphenylmethane over saturated hydro- CH2 CH2 carbons is due to the inductive effect of three rings and that less than half can be attributed to resonance stabili- ؊ zation of the ” (22). Figure 5. Resonance delocalization of charge in the benzyl anion. The example of triptycene (Figure 6A) demonstrates that inductive effects can play a role in determining hydrocarbon acidity. The pKa of triptycene (44; ref 23) is comparable to that of toluene and much greater than that of a saturated hydrocarbon. Despite the presence of three aromatic rings AB resonance delocalization of the triptycyl anion cannot occur ؊ (Figure 6B). Proton abstraction from a bridgehead carbon C atom generates the conjugate base that is forced to adopt a pyramidal conformation. An absence of necessary coplanar- ity precludes successful p orbital overlap. Stabilization of the C triptycyl anion occurs by an inductive electron withdrawal H mechanism through σ bonds involving the benzene rings. H This effect is apparent for other benzylic anions, including the benzyl anion itself. Greater s character in the bridgehead Figure 6. (A) Triptycene and (B) triptycyl anion. CϪH bond makes an additional acidifying contribution (23).

Aromaticity Effects Cyclopentadiene (Figure 7) is a remarkably acidic hy- H drocarbon having an experimentally measured pKa of 18 (24). Deprotonation results in delocalization of the cyclo- pentadienyl anionic charge over all five carbon atoms (Fig- ure 8). Resonance delocalization of charge and inductive Figure 7. Cyclopentadiene. electron withdrawal are clearly small contributory acidifying factors. The obeys Hückel’s rule—it is planar, has a total of six π electrons and a p orbital associ- ated with each carbon. An aromatic species is generated from a nonaromatic hydrocarbon (cyclopentadiene) that has an sp3 ؊ hybridized carbon atom present. The driving force of aro- ؊ maticity leads to the parent hydrocarbon having an acidity comparable to some aliphatic alcohols. The enormous size ؊ of this “aromatic effect” is evident on examining pKa values of other (Scheme IV). Seven canonical forms can be drawn for the tropylium anion. Addition of π elec- trons in this species shows there are eight (4n, an anti-aro- ؊ matic number, where n = 2). The extremely weak acidity of cycloheptatriene is attributable to great instability of its con- ؊ jugate base. Neither the parent hydrocarbon nor the conju- gate base adopts a planar conformation with the latter anion Figure 8. Five canonical forms of the cyclopentadienyl anion.

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H

؉ H ؊ ؉ H +؊ ؉ H

cycloheptatriene tropylium anion pKa = 36 Scheme V. Generation of the aromatic fluorenyl anion from fluo- rene.

Ph Ph H ؊ +؉ H

Ph Ph Ph Ph ؊ OH 1,2,3-triphenyl- 1,2,3-triphenyl- H cyclopropene cyclopropenyl ؊ pKa = 51 (lower limit) anion

Scheme IV. Generation of anti-aromatic anions from cycloheptatriene and 1,2,3-triphenylcyclopropene. The pKa values are from ref 25. Scheme VI. Generation of the fluoradenyl anion from fluoradene.

A H B H ؊

؊

Figure 9. (A) Indene and (B) . Figure 10. Fluoradenyl anion.

additionally representing an anti-aromatic species. The 1,2,3- bon atoms that represent an aromatic species. The negative triphenylcyclopropenyl anion has four π electrons (n = 1, charge is localized and each of the 18 carbons bears a nega- analogous to cyclobutadiene). Enormous angle strain exists tive charge of 0.00 (Figure 10). leading to an acidity similar to an unsubstituted alkane such A plot of experimental pKa values against aromatic sta- as ethane. bilization energies (delocalization energies, ∆Eπ) calculated Indene (pKa = 20.1; ref 26 ) and fluorene (pKa = 22.6; by Hückel molecular orbital (HMO) theory yields a linear ref 19b) are viewed as structural derivatives of cyclopentadiene correlation (Figure 11; ref 28). The HMO approach assumes (Figure 9). The successive decrease in acidity of cyclo- acidity is solely proportional to changes in π-bond energy pentadiene, indene, and fluorene is linked to a progressive resulting from conjugation differences between a hydrocar- decrease in aromatic character of the conjugate bases. This bon and its corresponding anion. This implies that σ-bond overshadows the acidifying effects of the benzene ring(s). The energy changes are constant and that any strain energies in fluorenyl anion has a total of 14 delocalized π electrons with the hydrocarbon are the same as those in the anion. Any sol- each of its 13 carbon atoms bearing a 0.077 negative charge vation or hyperconjugation effects are also neglected. The ∆Eπ (Scheme V). of the cyclopentadienyl anion is calculated by the Hückel Fluoradene (pKa = 13.8; ref 27 ) has two fluorene rings method to be 2.000β (29). The empirical aromatic stabiliza- fused together resulting in enhanced acidity compared to tion energy (derived from the heat of hydrogenation of ben- cyclopentadiene. There exists the possibility of forming a pla- zene relative to cyclohexene) equals 36 kcal mol᎑1 (30) and nar anion on deprotonation and extensive charge delocaliza- also corresponds to 2β. Conversion of cyclopentadiene to its tion taking place. The highlighted proton is removed by anion results in a large increase in delocalization energy (36 treatment with aqueous NaOH (Scheme VI). A sharp-eyed kcal mol᎑1). Significantly the correlation only holds for an- student will notice that the fluoradenyl anion in Scheme VI ions predicted to be coplanar. Triphenylmethane (whose an- has 20 π electrons associated with it (a 4n, or anti-aromatic, ion is subject to steric effects and deviates from coplanarity) number). One might predict the formation of this anion to is considerably less acidic than predicted by HMO theory. be energetically disfavored, and fluoradene to be correspond- Increasing electronic delocalization while maintaining ingly weakly acidic. It is however possible to draw canonical aromatic character on deprotonation further increases hydro- structures containing only 18 electrons spread over 18 car- carbon acidity (Table 3). Three of the four compounds in

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50

Table 3. pKa osf Some Polycyclic Aromatic Hydrocarbon toluene 40 Ceompound Sptructur Ka triphenylmethane a

K 30 p cyclopentadiene fluorene 20 H indene 34.1 CH 10. fluoradene 10 CCH 10 20 30 40 ؊1 ∆Eπ / (kcal mol ) 2

Figure 11. Plot of hydrocarbon aromatic stabilization energy (∆Eπ ) versus measured acidity (28).

H

31.2 C CH 9. Figure 12. 7H-Dibenzo[c,g]fluorene.

H H

؉ ؉ ؉ H

Scheme VII. Deprotonation of the benzenium ion.

Table 3 are based on the structure of 7H-dibenzo[c,g]fluorene H (Figure 12). An undergraduate exercise is to construct all ca- CH nonical forms of the anions derived from these molecules in 32.3 8. an attempt to link anionic stability with electronic delocal- HC CH ization. This reinforces concepts of resonance stabilization and “curly-arrow” notation.

Conclusions This article illustrates the remarkable range of experi- mentally measured hydrocarbon acidities. Discussion is lim- ited to neutral compounds containing solely the elements hydrogen and carbon. An even more acidic “hydrocarbon” is the benzenium ion (Scheme VII), which forms benzene on deprotonation. This species is only stable in superacid me- ᎑ dia and has an estimated pKa of < 10 (32). CH Acidity differences are reasoned by applying fundamen- 39.4 5. tal principles encountered by the students enrolled in an in- C H troductory organic chemistry course. The data provide an ideal springboard to discuss concepts of hybridization, reso- nance, induction, and aromaticity. Opportunities exist to outline limitations of these concepts when considered in iso- 3 lation from one another. Although hydrocarbons are gener- ally considered nonacidic, this is clearly not necessarily the case. Compound 3.4, Table 3, has a pKa of 5.9, meaning it is NOTE:sSaolvent i m.ixture of DMSO/HOAc/NaO AcfData from re at least four orders of magnitude more acidic than phenol 31.

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(aqueous pKa of 9.89; ref 1), although the latter pKa is sub- 8. Walsh, A. D. Discuss. Faraday Soc. 1947, 18–25. stantially lowered in the presence of DMSO (pKa = 12.4 in 9. Eglinton, G.; Jones, E. R. H.; Whiting, M. C. J. Chem. Soc. 70% DMSO; ref 33). As an extension students can be chal- 1952, 2873–2882. lenged to “design their own hydrocarbon” that may prove to 10. (a) Maksic, Z. B.; Eckert-Maksic, M. Tetrahedron 1969, 25, be even more acidic than the ones discussed herein. Several 5113–5114. (b) Randic, M.; Maksic, Z. B. Chem. Rev. 1972, software programs exist that allow prediction of pKa values, 72, 43–53. often to an accuracy of ±0.5 pKa units (34). 11. Carroll, F. A. Perspectives On Structure And Mechanism In Or- ganic Chemistry; Brooks/Cole: New York, 1998; p 42–43. Acknowledgment 12. Muller, N.; Pritchard, D. E. J. Chem. Phys. 1959, 31, 1471– 1476. The author would like to thank the reviewers for some 13. Closs, G. L.; Closs, L. E. J. Am. Chem. Soc. 1963, 85, 2022– extremely helpful suggestions regarding the preparation of this 2023. manuscript. 14. Streitwieser, A., Jr.; Caldwell, R. A.; Young, W. R. J. Am. Chem. Soc. 1969, 91, 529. WSupplemental Material 15. Streitwieser, A., Jr.; Young, W. R.; Caldwell, R. A. J. Am. Chem. Soc. 1969, 91, 527–528. A table containing the pKa values for all hydrocarbons 16. Streitwieser, A., Jr.; Boerth, D. W. J. Am. Chem. Soc. 1978, mentioned in this article is available in this issue of JCE 100, 755–759. Online. 17. Bordwell, F. G.; Algrim, D.; Vanier, N. R. J. Org. Chem. 1977, 42, 1817–1819. Notes 18. Daasbjerg, K. Acta. Chem. Scand. 1995, 49, 878–887. 19. (a) Bordwell, F. G.; Matthews, W. S.; Vanier, N. R. J. Am. 1. The most acidic proton in each structure is highlighted by Chem. Soc. 1975, 97, 442–443. (b) Matthews, W. S.; Bares, a bold H. J. E.; Bartmess, J. E.; Bordwell, F. G.; Cornforth, F. J.; Drucker, ᎑ ͞ 2. pKa represents log10 Ka, where Ka = kf kr for the equilib- G. E.; Margolin, Z.; McCallum, R. J.; Vanier, N. R.; rium: McCollum, G. J. J. Am. Chem. Soc. 1975, 97, 7006–7014. k 20. Bordwell, F. G.; Branca, J. C.; Hughes, D. L.; Olmstead, W. f ؉ ؊ .H A ؉؉B H B A N. J. Org. Chem. 1980, 45, 3305–3313 k r 21. Buncel, E. —Mechanistic And Isotopic Aspects; Ka is related to the rate constant for protonation of B (kf ) and depro- Elsevier Scientific: New York, 1975; p 3–4. + tonation of BH (kr). Since pKa values are recorded in solution, 22. Streitwieser, A., Jr.; Caldwell, R. A.; Granger, M. R. J. Am. anionic solvation makes kr the more significant rate constant. kf Chem. Soc. 1964, 86, 3578–3579. and kr are measures of kinetic rather than thermodynamic acidity. 23. Streitwieser, A., Jr.; Ziegler G. R. J. Am. Chem. Soc. 1969, 3. For comparison purposes, all quoted pKa values < 32 are 91, 5081–5084. in dimethylsulfoxide (DMSO) unless otherwise stated. 24. Bordwell, F. G.; Drucker, G. E.; Fried, H. E. J. Org. Chem. 4. Generally pKa determinations up to 33 are obtained by 1981, 46, 632–635. equilibrium methods involving colorimetry or spectroscopy. pKa 25. Breslow, R.; Chu, W. J. Am. Chem. Soc. 1970, 92, 2165. evaluation of less acidic hydrocarbons is achieved by electrochemi- 26. Bordwell, F. G.; Drucker, G. E. J. Org. Chem. 1980, 45, 3325– cal or isotopic exchange (H–D or H–T) techniques. 3328. 5. The SMO method involves optimizing parameters for all 27. Streitwieser, A., Jr.; Chang, C. J.; Hollyhead, W. B. J. Am. hybrid orbitals of all atoms in a molecule that maximizes the sum Chem. Soc. 1972, 94, 5292–5296. over all bonds of suitably scaled bond overlaps (10b). 28. Streitwieser, A., Jr. Molecular Orbital Theory For Organic Chem- ists; Wiley: New York, 1961; p 413–416. Literature Cited 29. Streitwieser, A., Jr.; Hammons, J. H. Prog. Phys. Org. Chem. 1965, 3, 41–80. 1. Perez, G. V.; Perez, A. L. J. Chem. Educ. 2000, 77, 910–915. 30. McMurry, J. Organic Chemistry, 5th ed.; Brooks-Cole: Pacific 2. Conant, J. B.; Wheland, G. W. J. Am. Chem. Soc. 1932, 54, Grove, CA, 2000; p 564–565. 1212–1221. 31. (a) Kuhn, R.; Rewicki, D. Angew. Chem. 1967, 79, 648–649. 3. McEwen, W. K. J. Am. Chem. Soc. 1936, 58, 1124–1129. (b) Kuhn, R.; Rewicki, D. Liebigs Ann. Chem. 1967, 704, 9– 4. For an example, see McMurry, J. Organic Chemistry, 5th ed.; 14. (c) Kuhn, R.; Rewicki, D. Liebigs Ann. Chem. 1967, 706, Brooks-Cole: Pacific Grove, CA, 2000; p 287. 250–261. 5. Chrisment, J.; Delpuech, J-J. J. Chem. Res. (Miniprint) 1978, 32. Isaacs, N. S. Physical Organic Chemistry, 2nd ed.; Longman: 9, 3701–3709. London, 1995; p 251. 6. (a) Buncel, E. Carbanions—Mechanistic And Isotopic Aspects; 33. Moutiers, G.; Le Guevel, E.; Villien, L.; Terrier, F. J. Chem. Elsevier Scientific: New York, 1975; p 20. (b) Carey, F. A. Soc., Perkin Trans. 2 1997, 7–13. Organic Chemistry; McGraw-Hill: New York, 1987; p 335. 34. As an example, see Advanced Chemistry Development Labo- 7. (a) Loudon, G. M. Organic Chemistry, 2nd ed.; Benjamin/ ratories (Toronto) ACD/pKa Calculator Page. http:// Cummings: Menlo Park, CA, 1988; p 566. (b) Carey, F. A. www.acdlabs.com/products/phys_chem_lab/pka/ (accessed Aug Organic Chemistry; McGraw-Hill: New York, 1987; p 335. 2003).

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