Pyridazine and Pyrazine Rings, Volume 5: Cinnolines, Phthalazines, and Quinoxalines(Chemistry of Heterocyclic Compounds: A Series Of Monographs)

The Chemistry of Heterocyclic Compounds, since its inception, has been recognized as a cornerstone of heterocyclic chemistry. Each volume attempts to discuss all aspects – properties, synthesis, reactions, physiological and industrial significance – of a specific ring system. To keep the series up-to-date, supplementary volumes covering the recent literature on each individual ring system have been published. Many ring systems (such as pyridines and oxazoles) are treated in distinct books, each consisting of separate volumes or parts dealing with different individual topics. With all authors are recognized authorities, the Chemistry of Heterocyclic Chemistry is considered worldwide as the indispensable resource for organic, bioorganic, and medicinal chemists.

Table of Contents:
Preface ix Part I. Ginnolines I. General Introduction to Cinnoline Derivatives. Preparation and Properties of Cinnoline 3 1. General Introduction to Cinnoline Derivatives 3 2. Preparation and Properties of Cinnoline 4 II. 4-Aryl-, 4-Acyl-, and 4-Carboxycinnolines 6 1. 4-Arylcinnolines 6 2. 4-Acylcinnolines 11 3. 4-Carboxycinnolines (Cinnoline-4-carboxylic Acids) 11 III. 4-Methylcinnolines 13 IV. 4-Hydroxycinnolines 16 1. Methods of Preparation 16 A. Richter Synthesis 16 B. Pfannstiel and Janecke Synthesis 17 C. Borsche Synthesis 17 2. Properties 23 A. 4-Hydroxycinnolines Other Than 4-IIydroxycinnoiine-3-carboxylic Acids 23 B. 4-Hydroxycinnoline-3-carboxylic Acids 24 V. 4-Chloro-, 4-Alkoxy-, and 4-Phenoxycinnolines 29 1. 4-ChlorocinnoIines 29 2. 4-Alkoxycinnolines 31 3. 4-Phenoxvcinnolines 32 VI. 4-Aminocinnolines 35 1. Primary Amino Compounds 35 2. Secondary Amino Compounds 36 A. 4-Arylaminocinnolines 36 B. 4-Dialkylaminoalkylaminocinnolines 36 C. 4-Hydroxylamino-7-acetylcinnolineoxime 38 VII. Cinnoline Quaternary Salts 39 A. Preparation 39 B. Structure 39 C. Reactions 43 VIII. Reduced Cinnolines 46 1. Reduced Cinnolines with Nonoxvgenated Rings 46 A. Dihydrocinnolines 46 B. Tetrahydrocinnolines 47 C. Hexahydrocinnolines 48 2. Reduced Cinnolines with Oxygenated Rings 48 A. Reduced 3- and 4-Hydroxycinnolines 48 B. l-Methyl-4-keto-l,4-dihydrocinnolines 48 C. Methyl 4-Keto-4,6-dihydrocinnolyl-6-nitronates 49 D. 3-Acetoxy-2-aryl-6-keto-2,6-dihydrocinnolines 49 E. 2-Pbenyl-3-keto-4-hydroxy-2,3,5,6,7,8-hexahydrocinnoline 51 IX. Cinnolines Containing Additional Fused Rings 52 1. 3,4-Benzocinnolines 52 2. Tetrahydro-3,4-benzocinnolines 57 3. Other Cinnolines with Additional Aromatic Rings 57 4. Cinnolines Containing Bridged Rings 61 5. Cinnolines Containing Fused Heterocyclic Rings 62 Part II. Phthalazines X. Phthalazines Unsubstituted in the Hetero Ring 69 1. Phthalazine 69 2. 5,6-Dihydroxy phthalazine 71 XI. 1-Alkyi-, 1-Aryl-, and 1,4-Diaryiphthalazlnes 72 1. 1-AIkyl- and 1-Arvlphthalazines 72 2. 1,4-Diarylphthalazines 76 XII. 1-Hydroxyphthalazines 78 A. Preparation 78 B. Properties 78 XIII. Alkyl, Aryl, and Acyl Derivatives of 4-(l-)Hydroxyphthalazines 84 1. O-Derivatives 84 2. N-Derivatives (3-Substituted-4-keto-3,4-dihydrophthalazines)... 85 A. Compounds without a l-Substituent; 3-Aryl-, 3-Alkyl-, and 3-Aralkyl-4-keto-3,4-dihydrophthalazines 85 B. Compounds with a l-Substituent 95 3. Derivatives of Unknown Structure 96 XIV. l-Hydroxy-3-aryl-3,4-dihydrophthalazine-4-acetic Acids 106 A. Preparation 106 B. Properties 108 XV. 3-Aryl-l-ketophthalazines 119 A. Preparation 119 B. Properties and Reactions 126 XVI. Methylated Derivatives of 3-Aryl-l-ketophthalazines 130 1. Derivatives of Compounds Containing a Hydrogen Atom at C4 130 A. l-Methoxy-4-alkoxy-3-aryl-3,4-dihydrophthalazines 130 B. l-Methoxy-3-arylphthalazinium Perchlorates 133 2. Derivatives of Compounds Containing a Methyl Group at C(: l-Methoxy-3-aryI-4-methylene-3,4-dihydrophthalazines 133 XVII. 1,4-Dlhydroxyphthalazines 140 A. Preparation 140 B. Properties 143 C. Chemiluminescence of Phthalazine Derivatives 153 XVIII. Monoalkyl and Monoacyl Derivatives of 1,4-Dihydroxyphthal-azines 157 1. O-Derivatives 157 2. .V-Derivatives (l-Hydroxy-3-substituted-4-keto-3,4-dihydro-phthalazines) 158 A. Compounds Containing No Substituent in the Benzene Ring 158 B. Compounds Containing a Substituent in the Benzene Ring 162 3. Derivatives of Unknown Structure 165 XIX. Dialkyl and Diacyl Derivatives of 1,4-Dihydroxyphthalazines 168 1. 1,4-Derivatives 168 2. 1,3-Derivatives (1-Alkoxy- and l-Acetoxy-3-substituted-4-keto-3,4-dihydrophthalazines) 169 A. Preparation 169 B. Properties 170 C. Structure of Alkoxy Compounds 173 3. 2,3-Derivatives 175 4. Derivatives of Unknown Structure 176 XX. 1-Halogeno- and 1,4-Dihalogenophthalazines 178 1. 1-Halogenophthalazines 178 2. 1,4-Dihalogenophthalazines 179 XXI. l-Aminophthalazines 183 XXII. Reduced Phthalazines 186 1. 3,4-Dihydrophthalazines  186 2. 1,2,3,4-Tetrahydrophthalazines 189 XXIII. Condensed Phthalazines and Azaphthalazines 191 1. 1',2'-3,4-Benziminazolo-3,4-dihydrophthalazines 191 2. Compounds Prepared from 1,4-Diketones 192 3. Miscellaneous Compounds 196 4. Azaphthalazines 198 Part III. Ouinoxalines XXIV. Preparation of Ouinoxalines from Primary Aromatic o-Di-amines and 1,2-Dicarbonyl Compounds 203 XXV. Ouinoxalines Unsubstituted in the Hetero Ring 228 Quinoxaline 228 6,6'-DiquinoxaIyl 229 XXVI. Quinoxaline A’-Oxides 232 A. Preparation 232 B. Properties 232 XXVII. 2-Hydroxy- and 2,3-Dihydroxyquinoxalines 235 1. 2-Hydroxyquinoxalines 235 A. Compounds Containing No Additional Substituent in the Hetero Ring 235 B. Compounds Containing an Additional (C3) Substituent in the Hetero Ring 236 Methylation of Hydroxyquinoxalines 241 2. 2,3-Dihydroxyquinoxalines 242 XXVIII. Quinoxaline-2-aldehydes 246 A. Preparation 246 B. Properties 246 C. 3-Hydroxyquinoxaline-2-aldehyde 246 XXIX. Quinoxaline-2-carboxyIic and-2,3-dicarboxylic Acids 250 1. Quinoxaline-2-earboxylic Acids 250 2. Quinoxaline-2,3-dicarboxyIic Acids 254 XXX. 2-Chloro- and 2,3-Dichloroquinoxallnes 258 1. 2-Chloroquinoxalines 258 2. 2,3-Dihalogenoquinoxalines 260 A. 2,3-DichIoroquinoxalines 260 B. 2,3-Dibromoquinoxaline 261 XXXI. 2-Amino- and 2,3-Diaminoquinoxatines  263 1. 2-Aminoquinoxalines 263 A. Primary Amino Compounds 263 B. Secondary Amino Compounds 264 C. 2-SulfonmidoquinoxaIines 265 D. Tertiary Amino Compound 265 2. Diaminoquinoxalines 265 A. Diprimary Amino Compounds 265 2.3- Diaminoquinoxaline 265 2.3- Diaminoquinoxaline-6-arsonic Acid 267 B. Primary-Secondary Amino Compounds 267 C. Disecondary Amino Compounds 269 XXXII. 2-Alkoxy-, 2,3-Dialkoxy-, and 2,3-Diaryloxyquinoxalines 270 1. 2-AlkoxyquinoxaIines 270 2. 2,3-Dialkoxy-and 2,3-Diaryloxyquinoxalines 271 XXXIII. 2-Methyl- and 2,3-Dimethylquinoxalines 273 1. 2-Methylquinoxalines 273 2. 2,3-Dimethylquinoxalines 277 XXXIV. Quinoxaline Quaternary Salts 286 A. Preparation 286 B. Properties 288 C. Decomposition by Alkali 290 D. Quinoxaline Cyanines 290 XXXV. Formation of Quinoxalines from Compounds Containing a Furan Ring 293 1. Conversion of 5-Hydroxy-2,5-diphenyl-4-keto-4,5-dihydrofurans and Related Compounds into Quinoxalines 293 2. Conversion of Coumaran-3-ones into Quinoxalines 296 A. 2-Hydroxy- and 2-Bromocoumaran-3-ones 296 B. Coumaran-2,3-diones 298 XXXVI. 2-Polyhydroxyalkylquinoxalines 300 1. Synthesis 300 2. Properties and Reactions 302 A. General 302 B. Decomposition by Alkali 304 C. Reactions with Phenylhydrazine 306 XXXVII. Reduced Quinoxalines 310 1. 1,2-and 1,4-Dihydroquinoxalines 310 A. Compounds Containing No Hydroxyl or Carbonyl Group in the Hetero Ring 310 B. Compounds Containing a Hydroxyl or Carbonyl Group in the Hetero Ring 310 (а) l-Substituted-2-keto-1,2-dihydroquinoxalines 310 (б) 1,2- and 1,4-Dihydroqu inoxalines Having Hydroxyl Groups at C2 or C3 318 2. 1,2,3,4-Tetrahydroquinoxalines 325 A. 1,2,3,4-Tetrahydroquinoxalines Containing No Oxygen Atom Attached to the Hetero Ring 325 Preparation 325 Properties 326 Stereoisomerism of 1,2,3,4-Tetrahydroquinoxalines 326 I,4-EndoalkyIene-l,2,3,4-tetrahydroquinoxalines 326 B. 1,2,3,4-Tetrahydroquinoxalines Containing an Oxygen Atom Attached to the Hetero Ring 329 XXXVIII. Condensed Quinoxalines 332 1. Quinoxalines Condensed with Carboeyclie Rings 332 A. 5,6-Benzoquinoxalines 332 B. 5,6,7,8-Dibenzoquinoxalines 338 C. Glucazidone and Derivatives 338 D. Other Condensed Quinoxalines 341 2. Quinoxalines Condensed with Nitrogenous Heterocyclic Rings 346 A. Pyrroloquinoxalines 346 B. Pyridoquinoxalines 348 C. Pyrazoloquinoxalines (Flavazoles) 348 D. Glyoxalinoquinoxalines 353 E. Triazoloquinoxalines 353 F. Pyridazoquinoxalines 354 XXXIX. Azaquinoxalines 356 Appendix I. Ultraviolet Absorption Spectra of Cinnoiine and Quinoxaline Derivatives 358 Appendix II. Basic Strengths of Cinnoiine, Phthalazine, and Quinoxaline Derivatives 363 Appendix III. Antibacterial and Parasiticidal Activities of Cinnoiine and Quinoxaline Derivatives 364 Index 367

About the Author :
J. C. Simpson is the editor of Pyridazine and Pyrazine Rings: (Cinnolines, Phthalazines, and Quinoxalines), Volume 5, published by Wiley.