KLAUS HOFMANN, Professor of Biochemistry, Medical School, University of Pittsburgh, PA.

• Preface ixSection I Chemistry of Classes and DerivativesI. General Properties and Structure of the Imidazoles 3A. Nomenclature 3B. Physical Properties 5C. Chemical Properties 13D. Structural Considerations 17E. Tautomeric Character 26II. The Alkyl- and Arylimidazoles 33A. Synthetic Procedures 33B. Properties and Chemical Behavior 45III. The Oxo- and Hydroxyimidazoles and Their Sulfur Analogues 55A. The Oxoimidazoles 55B. The Hydroxyalkylimidazoles 99IV. The Halogenoimidazoles 111A. Bromoimidazoles 111B. Chloroimidazoles 119C. Chloroalky limidazoles 121V. The Nitro-, Arylazo-, and Aminoimidazoles 127A. Nitroimidazoles 127B. Arylazoimidazolcs 136C. Aminoimidazoles 141D. Histamine 143VI. The Imidazolecarboxylic and Sulfonic Acids 175A. Imidazolecarhoxylic Acids 175B. Imidazolesulfonic Acids 206VII. The Imidazolines, 2-Imidazolidones, 2-Imidazolidinethiones, 2-Iminoimidazolidines, and Imidazolidines 213A. Nomenclature 213B. 2-ImidazoIines 213C. 2-Imidazolidones 226D. 2-Imidazolidinethiones 234E. 2-Iminoimidazolidines 238F. Imidazolidines 242VIII. The Benzimidazoles 247A Nomenclature 247B General Properties 248C. Synthetic Procedures 258D. The 1-Acylbenzimidazoles and tire Bamberger Reaction 273E. The Alkyl- and Arylbenzimidazoles and 1,3-Dialkyibenzimiduzolium Salts 276F. The Oxo- and Hydroxybenzimidazolcs and Their Sulfur Analogues 284G The Halogenobenzimidazoles 300H The Nitro- and Aminobenzimidazoles 304I. The Benzimidazolecarboxylic and Sulfonic Acids 313Section 2 Systematic Survey and Bibliography Key to Abbreviations 320I. Imidazoles 327A. Alkyl-and Arylimidazoles 327B Alkyl- and Arylimidazolium Salts 330C. Oxo- and Hydroxyimidazolos and Their Sulfur Analogues 330D. Halogenoimidazoles 342E. Nitroimidazoles 345F. Arylazoimidazoles 346G. Aminoimidazoles 347H. Cyano- and Isocyanatoimidazolcs 351I. Tinidazolcearboxylic Acids 352J. Imidnzolcsulftnic and Sulfonic Acids 363K. Imidazole Arscnicals 363L. Isoimidazolcs 363M. Heteroring-Substituted Imidazoles 364N Bi- and Bisimidazoles 366II. Imidazolines 367A. 2-Tmidazolines 367B. 3-Imidazolines 372C. 4-Imidazolines 372D. Heteroring-Substituted 2-Imiriaznliiics 372III. Imidazolidines 373A. Alkyl- and Arylimidazolidines 373B. 4- and 5-Imidazolidones 378C. 2-Iraidazolidinethiones (Ethylenethioureas) 378D. 4-Imidazolidinethiones 379E. 2-Iminoimiriazoliriines (Ethyleneguanidines) 379V. Benzimidazoles 379A. Alkyl- and Arylbenrimidazoles 379B. Alkyl- and Arylbenzimidazolium Salts 382C. Oxo-and Hydroxybenzimidazoles and Their Sulfur Analogues 382D. Halogeno-, Halogenoalkyl-, and Halogenoarylbenzimidazoles 388E. Nitro-, Nitroalkyl-, and Nitroarylbenzimidazoles Including Those Containing Additional Functional Groups 388F. Aminobenzimidazoles 389G. Cyanobenzimidazoles 394H Benzimidazolecarboxylic Acids 395I. Benzimidazolcsulfonic Acids, Sulfoalkyl-, and Sulfoarylbenzimidazoles 398J. Benzimidazole Arscnicals 398K. 2,3-DihydroIxaizimidazoles (Benzimidizolines) 399L. Heteroring-Substituted Benzimidazoles 399M Bi-, Di-, and Bisbonzimidazoles 401Bibliography 401Subject Index 421

KLAUS HOFMANN, Professor of Biochemistry, Medical School, University of Pittsburgh, PA.

• Preface ixSection I Chemistry of Classes and DerivativesI. General Properties and Structure of the Imidazoles 3A. Nomenclature 3B. Physical Properties 5C. Chemical Properties 13D. Structural Considerations 17E. Tautomeric Character 26II. The Alkyl- and Arylimidazoles 33A. Synthetic Procedures 33B. Properties and Chemical Behavior 45III. The Oxo- and Hydroxyimidazoles and Their Sulfur Analogues 55A. The Oxoimidazoles 55B. The Hydroxyalkylimidazoles 99IV. The Halogenoimidazoles 111A. Bromoimidazoles 111B. Chloroimidazoles 119C. Chloroalky limidazoles 121V. The Nitro-, Arylazo-, and Aminoimidazoles 127A. Nitroimidazoles 127B. Arylazoimidazolcs 136C. Aminoimidazoles 141D. Histamine 143VI. The Imidazolecarboxylic and Sulfonic Acids 175A. Imidazolecarhoxylic Acids 175B. Imidazolesulfonic Acids 206VII. The Imidazolines, 2-Imidazolidones, 2-Imidazolidinethiones, 2-Iminoimidazolidines, and Imidazolidines 213A. Nomenclature 213B. 2-ImidazoIines 213C. 2-Imidazolidones 226D. 2-Imidazolidinethiones 234E. 2-Iminoimidazolidines 238F. Imidazolidines 242VIII. The Benzimidazoles 247A Nomenclature 247B General Properties 248C. Synthetic Procedures 258D. The 1-Acylbenzimidazoles and tire Bamberger Reaction 273E. The Alkyl- and Arylbenzimidazoles and 1,3-Dialkyibenzimiduzolium Salts 276F. The Oxo- and Hydroxybenzimidazolcs and Their Sulfur Analogues 284G The Halogenobenzimidazoles 300H The Nitro- and Aminobenzimidazoles 304I. The Benzimidazolecarboxylic and Sulfonic Acids 313Section 2 Systematic Survey and Bibliography Key to Abbreviations 320I. Imidazoles 327A. Alkyl-and Arylimidazoles 327B Alkyl- and Arylimidazolium Salts 330C. Oxo- and Hydroxyimidazolos and Their Sulfur Analogues 330D. Halogenoimidazoles 342E. Nitroimidazoles 345F. Arylazoimidazoles 346G. Aminoimidazoles 347H. Cyano- and Isocyanatoimidazolcs 351I. Tinidazolcearboxylic Acids 352J. Imidnzolcsulftnic and Sulfonic Acids 363K. Imidazole Arscnicals 363L. Isoimidazolcs 363M. Heteroring-Substituted Imidazoles 364N Bi- and Bisimidazoles 366II. Imidazolines 367A. 2-Tmidazolines 367B. 3-Imidazolines 372C. 4-Imidazolines 372D. Heteroring-Substituted 2-Imiriaznliiics 372III. Imidazolidines 373A. Alkyl- and Arylimidazolidines 373B. 4- and 5-Imidazolidones 378C. 2-Iraidazolidinethiones (Ethylenethioureas) 378D. 4-Imidazolidinethiones 379E. 2-Iminoimiriazoliriines (Ethyleneguanidines) 379V. Benzimidazoles 379A. Alkyl- and Arylbenrimidazoles 379B. Alkyl- and Arylbenzimidazolium Salts 382C. Oxo-and Hydroxybenzimidazoles and Their Sulfur Analogues 382D. Halogeno-, Halogenoalkyl-, and Halogenoarylbenzimidazoles 388E. Nitro-, Nitroalkyl-, and Nitroarylbenzimidazoles Including Those Containing Additional Functional Groups 388F. Aminobenzimidazoles 389G. Cyanobenzimidazoles 394H Benzimidazolecarboxylic Acids 395I. Benzimidazolcsulfonic Acids, Sulfoalkyl-, and Sulfoarylbenzimidazoles 398J. Benzimidazole Arscnicals 398K. 2,3-DihydroIxaizimidazoles (Benzimidizolines) 399L. Heteroring-Substituted Benzimidazoles 399M Bi-, Di-, and Bisbonzimidazoles 401Bibliography 401Subject Index 421

KLAUS HOFMANN, Professor of Biochemistry, Medical School, University of Pittsburgh, PA.

• Preface ixSection I Chemistry of Classes and DerivativesI. General Properties and Structure of the Imidazoles 3A. Nomenclature 3B. Physical Properties 5C. Chemical Properties 13D. Structural Considerations 17E. Tautomeric Character 26II. The Alkyl- and Arylimidazoles 33A. Synthetic Procedures 33B. Properties and Chemical Behavior 45III. The Oxo- and Hydroxyimidazoles and Their Sulfur Analogues 55A. The Oxoimidazoles 55B. The Hydroxyalkylimidazoles 99IV. The Halogenoimidazoles 111A. Bromoimidazoles 111B. Chloroimidazoles 119C. Chloroalky limidazoles 121V. The Nitro-, Arylazo-, and Aminoimidazoles 127A. Nitroimidazoles 127B. Arylazoimidazolcs 136C. Aminoimidazoles 141D. Histamine 143VI. The Imidazolecarboxylic and Sulfonic Acids 175A. Imidazolecarhoxylic Acids 175B. Imidazolesulfonic Acids 206VII. The Imidazolines, 2-Imidazolidones, 2-Imidazolidinethiones, 2-Iminoimidazolidines, and Imidazolidines 213A. Nomenclature 213B. 2-ImidazoIines 213C. 2-Imidazolidones 226D. 2-Imidazolidinethiones 234E. 2-Iminoimidazolidines 238F. Imidazolidines 242VIII. The Benzimidazoles 247A Nomenclature 247B General Properties 248C. Synthetic Procedures 258D. The 1-Acylbenzimidazoles and tire Bamberger Reaction 273E. The Alkyl- and Arylbenzimidazoles and 1,3-Dialkyibenzimiduzolium Salts 276F. The Oxo- and Hydroxybenzimidazolcs and Their Sulfur Analogues 284G The Halogenobenzimidazoles 300H The Nitro- and Aminobenzimidazoles 304I. The Benzimidazolecarboxylic and Sulfonic Acids 313Section 2 Systematic Survey and Bibliography Key to Abbreviations 320I. Imidazoles 327A. Alkyl-and Arylimidazoles 327B Alkyl- and Arylimidazolium Salts 330C. Oxo- and Hydroxyimidazolos and Their Sulfur Analogues 330D. Halogenoimidazoles 342E. Nitroimidazoles 345F. Arylazoimidazoles 346G. Aminoimidazoles 347H. Cyano- and Isocyanatoimidazolcs 351I. Tinidazolcearboxylic Acids 352J. Imidnzolcsulftnic and Sulfonic Acids 363K. Imidazole Arscnicals 363L. Isoimidazolcs 363M. Heteroring-Substituted Imidazoles 364N Bi- and Bisimidazoles 366II. Imidazolines 367A. 2-Tmidazolines 367B. 3-Imidazolines 372C. 4-Imidazolines 372D. Heteroring-Substituted 2-Imiriaznliiics 372III. Imidazolidines 373A. Alkyl- and Arylimidazolidines 373B. 4- and 5-Imidazolidones 378C. 2-Iraidazolidinethiones (Ethylenethioureas) 378D. 4-Imidazolidinethiones 379E. 2-Iminoimiriazoliriines (Ethyleneguanidines) 379V. Benzimidazoles 379A. Alkyl- and Arylbenrimidazoles 379B. Alkyl- and Arylbenzimidazolium Salts 382C. Oxo-and Hydroxybenzimidazoles and Their Sulfur Analogues 382D. Halogeno-, Halogenoalkyl-, and Halogenoarylbenzimidazoles 388E. Nitro-, Nitroalkyl-, and Nitroarylbenzimidazoles Including Those Containing Additional Functional Groups 388F. Aminobenzimidazoles 389G. Cyanobenzimidazoles 394H Benzimidazolecarboxylic Acids 395I. Benzimidazolcsulfonic Acids, Sulfoalkyl-, and Sulfoarylbenzimidazoles 398J. Benzimidazole Arscnicals 398K. 2,3-DihydroIxaizimidazoles (Benzimidizolines) 399L. Heteroring-Substituted Benzimidazoles 399M Bi-, Di-, and Bisbonzimidazoles 401Bibliography 401Subject Index 421