THEORETICAL AND COMPUTATIONAL CHEMISTRY

Theoretical Organic Chemistry

Edited by

Cyril Parkanyi

Department of Chemistry and Biochemistry Florida Atlantic University

Boca Raton, FL 33431-0991, USA

1998

ELSEVIER

Amsterdam - Lausanne - New York - Oxford - Shannon - Singapore - Tokyo

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TABLE OF CONTENTS

Chapter 1. Theoretical Organic Chemistry: Looking Back in Wonder, Jan J.C. Mulder 1

1. Personal Preface 1 2. Introduction 3 3. The First Period (1850-1875) 4 4. Interlude 1 6 5. The Second Period (1910-1935) 8 6. Interlude 2 12 7. The Third Period 14 8. Epilogue 20

Chapter 2. Inter-Relations between VB & MO Theories for Organic TC-Networks, Douglas J. Klein 33

1. Broad Motivation and Aim - Graph Theory 33 2. VB and MO Models 35 3. MO-Based Elaborations and Cross-Derivations 38 4. HückelRule 41 5. Polymers and Excitations 44 6. Prospects 47

Chapter 3. The Use of the Electrostatic Potential for Analysis and Prediction of Intermolecular Interactions, ToreBrinck 51

1. Introduction 51 2. Methodological Background 51

2.1. Definition and physical significance 51 2.2. Spatial minima in the electrostatic potential 52 2.3. Surface electrostatic potential 55 2.4. Geometries ofweak complexes 58 2.5. Polarization corrections to the interaction energy 60 2.6. Charge transfer and the average local ionization energy 61 2.7. Characters of the different interaction quantities 62

3. Analysis of Site-Specific Interactions 65 3.1. Hydrogen bonding 65 3.2 Frequency shifts 71 3.3. Protonation 71

4. Analysis of Substituent Effects on Chemical Reactivity 73 4.1. Background 73 4.2. Acidities of aromatic Systems 73 4.3. O-H bond dissociation energies in phenols 77

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5. Statistically-Based Interaction Indices 81 5.1. Background 81 5.2. Definitions 82 5.3. Predictionsofoctanol/waterpartitioncoefficients 83

6. Summary 87

Chapter 4. Exploring Reaction Outcomes through the Reactivity-Selectivity Principle Estimated by Density Functional Theory Studies, Branko S. Jursic 95

1. Introduction 95 2. Computational Methodology 96 3. Basics for the Reactivity-Selectivity Approach 96 4. The Diels-Alder Reaction 101

4.1. Diels-Alder reaction of cyclopropene with butadiene 102 4.2. Diels-Alder reaction of cyclopropene with furan 105

5. Ring-Opening Reactions 108 5.1. Cyclobutene ring opening 109 5.2. Influence of substituents upon the reactivity of cyclobutene

ring opening 111 6. Radical Reactions 117

6.1. Trichloromethyl radical proton abstraction reaction 117 6.2. Intramolecular radical addition to carbon-carbon double bond 119

7. Reactivity and Stability of Carbocations 123 7.1. Hydride affinity as a measure of carbocation reactivity 123 7.2. Strain energies as a measure of reactivity 126

8. Conclusion 127

Chapter 5. A Hardness and Softness Theory of Bond Energies and Chemical Reactivity, Jose L. Gäzquez 135

1. Introduction 135 2. Reactivity Parameters 136

2.1. The density functional theory framework 136 2.2. Fundamental concepts 137

3. Energy and Hardness Differences 140 3.1. Bond energies 143 3.2. Activation energies 146

4. Catalyzed Reactions and Reactions in Solution 148 5. Concluding Remarks 150

Chapter 6. Molecular Geometry as a Source of Chemical Information for 7t-Electron Compounds, Tadeusz M. Krygowski and Michal K. Cyraiiski 153

Abstract 153 Introduction 154 1. Heat of Formation Derived from the Molecular Geometry: The Bond Energy

Derived from CC Bond Lengths 155

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1.1. Energy content of individual phenyl rings in various topological and chemical embedding 156

1.2. Ring energy content of benzene rings in benzenoid hydrocarbons .... 157 1.3. Ring energy content in the ring of TCNQ moieties involved in

electron-donor-acceptor (EDA) complexes and salts 160 1.4. Ring energy content depending on the intermolecular H-bonding:

the case ofp-nitrosophenolate anion 161 1.5. Ring energy content as a quantitative measure of fiilfilling the Hückel

4n + 2 rule for derivatives of fulvene and heptafiilvene 162 1.6. Estimation of H...0 and H...N energy of interactions in H-bonds 163

2. Canonical Structure Weights Derived frorn the Molecular Geometry 165 2.1. Principles of the HOSE model 166 2.2. Substituent effect illustrated by use of the HOSE model 168 2.3. Structural evidence against the classical through resonance concept

in/j-nitroaniline and its derivatives 170 2.4. Does the nitro group interact mesomerically with the ring

in nitrobenzene? 172 2.5. Angular group induced bond alternation - a new substituent effect

detected by molecular geometry 174 3. Substituent Effect on the Molecular Geometry 177 4. Aromatic Character Derived from Molecular Geometry 180 5. Conclusions 183

Chapter 7. Average Local Ionization Energies: Significance and Applications, Jane S. Murray and Peter Politzer 189

1. Introduction 189 2. Average Local Ionization Energies of Atoms 190 3. Average Local Ionization Energies ofMolecules 191

3.1. Applications to reactivity 191 3.2. Characterization ofbonds 198

4. Summary 199

Chapter 8. Intrinsic Proton Affinity of Substituted Aromatics, Zvonimir B. Maksic and Mirjana Eckert-Maksic 203

1. Introduction 203 2. Absolute Proton Affinities 203

2.1. Experimental basicity scales 203 2.2. Theoretical modeis for calculating absolute PAs 204 2.3. Proton affinities in monosubstituted benzenes 206 2.4. Proton affinities in polysubstituted benzenes - the additivity rule 211

2.4.1. Increments 211 2.4.2. Disubstituted benzenes - the independent substituent

approximation 214 2.4.3. Polysubstituted benzenes 215 2.4.4. The ipso protonation 217

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2.4.5. Limitations of the MP2(I) model - the aniline story 222 2.4.6. Proton affinities of larger aromatics - naphthalenes 223

3. Miscellaneous Applications of the Additivity Rule 225 4. Conclusion 228

Chapter 9. Dipole Moments of Aromatic Heterocycles, Cyril Pärkänyi and Jean-Jacques Aaron 233

1. Introduction 233 2. Experimental Ground-State Dipole Moments 235

2.1. Dielectric constant methods 235 2.2. Microwave methods 238 2.3. The Stark effect method 239 2.4. Molecular beam method 239 2.5. Electric resonance method 239 2.6. Raman spectroscopy 239 2.7. Sign and directum of the dipole moment 239

3. Calculated Ground-State Dipole Moments 241 3.1. Empirical methods 241 3.2. Semiempirical methods 244 3.3. Ab initio methods 245 3.4. Semiempirical and ab initio methods - a comparison 245

4. Experimental Excited-State Dipole Moments 245 5. Calculated Excited-State Dipole Moments 249 6. Conclusion 251

Chapter 10. New Developments in the Analysis of Vibrational Spectra. On the Use of Adiabatic Internal Vibrational Modes, Dieter Cremer, J. Andreas Larsson, and Elfi Kraka 259

1. Introduction 259 2. The Concept ofLocalized Internal Vibrational Modes 260 3. The Basic Equations of Vibrational Spectroscopy 263 4. Previous Attempts of Defining Internal Vibrational Modes 266 5. Definition of Adiabatic Internal Modes 267 6. Definition of Adiabatic Internal Force Constant, Mass, and Frequency 271 7. Characterization of Normal Modes in Terms of Internal Vibrational Modes ... 273 8. Definition of Internal Mode Amplitudes^ 277 9. Analysis of Vibrational Spectra in Terms of Adiabatic Internal Modes 281 10. Correlation of Vibrational Spectra of DifFerent Molecules 288 11. Derivation of Bond Information from Vibrational Spectra 297 12. Adiabatic Internal Modes from Experimental Frequencies 3 02 13. A Generalization ofBadger's Rule 308 14. Intensities of Adiabatic Internal Modes 312 15. Investigation of Reaction Mechanism with the Help of the CNM Analysis .... 316 16. Conclusions 324

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Chapter 11. Atomistic Modeling of Enantioselection: Applications in Chiral Chromatography, KennyB. Lipkowitz 329

Introduction 329 1. Stereochemistry 330 2. Chromatography 332 3. Molecular Modeling 335 4. Chiral Stationary Phase Systems 335 5. Modeling Enantioselective Binding 336 6. TypeICSPS 336

6.1. Motif based searches 337 6.2. Automated search strategies 341

7. TypelICSPS 354 8. Type IIICSPS 363 9. Type IV CSPS 370 10. Type V CSPS 371 Summary 375

Chapter 12. Theoretical Investigation of Carbon Nets and Molecules, Alexandra T. Balaban 381

1. Introduction 381 2. Infinite Planar Nets ofs/?2-Hybridized Carbon Atoms 381

2.1. Graphite: two-dimensional infinite sheets 381 2.2. Other planar lattices with ,sp2-hybridized carbon 382 2.3. Tridimensional infinite lattices with s/?2-hybridized carbon atoms 3 84 2.4. Graphitic cones with sp -hybridized carbon atoms 384

3. Infinite Nets of 3p3-Hybridized Carbon Atoms 385 3.1. Diamond: three-dimensional infinite network 385 3.2. Other Systems with sp -hybridized carbon atoms 386 3.3. Holes bordered by heteroatoms within the diamond lattice 386

4. Infinite Nets with Both sp - and sp -Hybridized Carbon Atoms 387 4.1. Local defects in the graphite lattice 387 4.2. Local defects in the diamond lattice 389 4.3. Block-copolymers of graphite and diamond (diamond-graphite

hybrids) 390 4.4. Systems with regularly alteraating sp Isp -hybridized carbon atoms . 390

5. Infinite Chains of^p-Hybridized Carbon Atoms 391 5.1. Chams of jp-hybridized carbon atoms: one-dimensional System 391 5.2. Heteroatom Substitution inside polyacetylenic chains 391

6. Molecules with sp2-Hybridized Carbon Atoms 391 6.1. Fullerenes 391 6.2. Nanotubes and capsules 393 6.3. Carbon cages and nanotubes including oxygen, nitrogen or boron

heteroatoms 395 7. Molecules with sp- and sp -Hybridized Carbon Atoms 398

7.1. Cages with sp- and .sp2-hybridized carbon atoms 398

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7.2. Molecules with ̂ p-hybridized carbonatoms 398 7.3. Covalently-bonded nested cages with sp- and/or ^p3-hybridized

carbon, or carbon and Silicon atoms 399 8. Conclusions: from Radioastronomy to Remedying Dangling Bonds

Carbon Nets 400

Chapter 13. Protein Transmembrane Structure: Recognition and Prediction by Using Hydrophobicity Scales through Preference Functions, Davor Juretic, Bono Lucio, DamirZucic, and Nenad Trinajstic 405

1. Introduction 405 2. Methods 407

2.1. Selecting protein databases fortraining and fortesting 407 2.2. Main Performance parameters used to judge the prediction quauty .. 409 2.3. Hydrophobie moment profile 410

2.3.1. The training procedure for the preference funetions method 411 2.3.2. The testing procedure 411 2.3.3. Decision constants choiee 411 2.3.4. Collection ofenvironments and smoothing procedure 412 2.3.5. Filtering procedure 412 2.3.6. Predicting transmembrane ß-strands (TMBS) 413 2.3.7. Adopted cross-validation technique 414

3. Results 414 3.1. Conformational preference for transmembrane a-helix is strongly

dependent on sequence hydrophobic environment for most amino aeidtypes 414

3.2. Expected and predicted length distribution for transmembrane helical segments 416

3.3. What is the optimal choiee of the sliding window size? 418 3.4. How do the results depend on different devices used in the SPLIT

algorithm? 418 3.5. What are the best scales of amino aeid attributes? 420 3.6. The prediction results with Kyte-Doolittle preference funetions 422 3.7. Testing for false positive predictions in membrane and soluble

proteins of crystallographically known structure 424 3.8. Cross-validation, overtraining and sensitivity to the choiee

of protein data base 427 3.9. Comparisons with other methods 429 3.10. Using prediction profiles with both oc and ß motifs 432

4. Discussion 434

Chapter 14. Polycyclic Aromatic Hydrocarbon Carcinogenicity: Theoretical Modelling and Experimental Facts, Läszlö von Szentpaly and Ratna Ghosh 447

1. Introduction to Chemical Carcinogenesis 447 2. PAH Carcinogenicity and Theoretical Models 450

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2.1. The bay-region theory 453 2.2. The MCS model 454

2.2.1. Metabolie factor 455 2.2.2. Carbocation formation 456 2.2.3. Size factor 458 2.2.4. Performance and limitations 458

3. DNABinding ofCarcinogenicHydrocarbon Metabolites 461 4. Hydrolysis and PAH Carcinogenicity 472 5. Molecular Modelling of Intercalated PAH Triol Carbocations 477

5.1. Ab initio calculations onPAHTC conformations 478 5.2. AMBER modelling of intercalated PAHTC-DNA complexes 481

6. Conclusion 487

Chapter 15. Cycloaddition Reactions Involving Heterocyclic Compounds as Synthons in the Preparation of Valuable Organic Compounds. An Effective Com-bination of a Computational Study and Synthetic Applications of Hetero-cycle Transformations, Branko S. Jursic 501

1. Introduction 501 2. Computational Methodology 502 3. Diels-Alder Reactions with Five-Membered Heterocycles with One

Heteroatom 502 3.1. Furan, pyrrole, and thiophene as dienophiles in reaction with

acetylene, ethylene, and cyclopentadiene 502 3.2. Addition ofbenzyne to furan, pyrrole, and thiophene 513 3.3. Cycloaddition reactions with pyrrole as diene for Diels-Alder

reaction 518 3.4. Diels-Alder reactions with benzoffc]- and benzo[c]-fused hetero­

cycles 529 4. Diels-Alder Reactions with Five-Membered Heterocycles with Two Hetero-

atoms 539 4.1. Addition of acetylene, ethylene, and cyclopropene to heterocycles

with heteroatoms in the 1 and 2 positions 542 4.2. Addition of acetylene, ethylene, and cyclopropene to heterocycles

with heteroatoms in the 1 and 3 positions 546 5. Diels-Alder Reactions with Five-Membered Heterocycles with Three Hetero­

atoms 549 5.1. Addition of acetylene, ethylene, and cyclopropene to heterocycles

with heteroatoms in 1, 2, and 3 positions 552 5.2. Addition of cyclopropene to heterocycles with heteroatoms in the

1, 2, and 5 positions 554 5.3. Addition of acetylene, ethylene, and cyclopropene to heterocycles

with heteroatoms in the 1,2, and 4 positions 555 5.4. Further investigation of the role of 1,3,4-oxadiazole as a diene in

Diels-Alder reactions 558

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6. Cycloaddition Reactions with Activated Heterocycles That Have Two or Three Heteroatoms 563

6.1. Activationof 1,2-diazole as a diene for Diels-Alder reaction 563 6.2. Transformation of cyclic malonohydrazides into the Diels-Alder

reactive 1,3-diazole 567 6.3. Quatemization of nitrogen atom as a way to activate 1,3-diazole,

and 1,3,4-triazole as a diene for the Diels-Alder reaction 569 6.4. Oxidation of a sulfur atom: a way to activate 1,3-thiazole and

1,3,4-thiadiazole as dienes for the Diels-Alder reaction 571 7. Conclusion 574

Chapter 16. Triplet Photoreactions; Stmctural Dependence of Spin-Orbit Coupling and Intersystem Crossing in Organic Biradicals, Martin Kiessinger 581

1. Introduction 581 2. Basic Theory 582

2.1. Wave functions and Operators 582 2.2. Matrix elements between bonded functions 584 2.3. Evaluation of spin-orbit integrals 586

3. Spin-Orbit Coupling and Intersystem Crossing in Biradicals 587 3.1. Carbene 588 3.2. Ethylene 590 3.3. Trimethylene 592 3.4. 1,2-Dimethyltrimethylene 595 3.5. Tetramethylene 596 3.6. Oxatetramethylene 599

4. Models for Spin-Orbit Coupling 600 4.1. The 2-in-2 model 600 4.2. Symmetry considerations 603 4.3. The "through-space" vector model 603

5. Conclusions 606

Index 611