Pyridazine and Pyrazine Rings: (Cinnolines, Phthalazines, and Quinoxalines), Volume 5

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