The Naphthyridines, Volume 63

Chapter 1 Primary Syntheses of 1,5-Naphthyridines 1

1.1 From a Single Aliphatic Substrate 1

1.2 From a Single Pyridine Substrate 2

1.2.1 By Formation of the N1,C2-Bond 2

1.2.2 By Formation of the C3,C4-Bond 3

1.2.3 By Formation of the C4,C4a-Bond 4

1.3 From a Pyridine Substrate with One Synthon 5

1.3.1 Where the Synthon Supplies One Atom 5

1.3.2 Where the Synthon Supplies Two Atoms 6

1.3.3 Where the Synthon Supplies Three Atoms 7

1.4 From a Pyridine Substrate and Two Synthons 9

1.5 From Other Heterocyclic Substrates 10

Chapter 2 1,5-Naphthyridine, Alkyl-1,5-Naphthyridines, and Aryl-1,5-Naphthyridines 13

2.1 1,5-Naphthyridine 13

2.1.1 Preparation of 1,5-Naphthyridine 13

2.1.2 Properties of 1,5-Naphthyridine 14

2.1.3 Reactions of 1,5-Naphthyridine 16

2.2 Alkyl- and Aryl-1,5-Naphthyridines 19

2.2.1 Preparation of Alkyl- and Aryl-1,5-Naphthyridines 20

2.2.2 Reactions of Alkyl- and Aryl-1,5-Naphthyridines 22

Chapter 3 Halogeno-1,5-Naphthyridines 25

3.1 Preparation of Halogeno-1,5-Naphthyridines 25

3.1.1 By Direct Halogenation 25

3.1.2 By Halogenolysis of 1,5-Naphthyridinones or the Like 26

3.1.3 By the Meissenheimer Reaction on 1,5-Naphthyridine N-Oxides 29

3.1.4 By Miscellaneous Procedures 31

3.2 Reactions of Halogeno-1,5-Naphthyridines 31

3.2.1 Alcoholysis or Phenolysis of Halogeno-1, 5-Naphthyridines 31

3.2.2 Aminolysis of Halogeno-1,5-Naphthyridines 34

3.2.3 Other Reactions of Halogeno-1,5-Naphthyridines 38

Chapter 4 Oxy-1,5-Naphthyridines 43

4.1 Tautomeric 1,5-Naphthyridinones and Extranuclear Hydroxy-1,5-Naphthyridines 43

4.1.1 Preparation of Tautomeric 1,5-Naphthyridinones and the Like 44

4.1.2 Reactions of Tautomeric 1,5-Naphthyridinones and the Like 46

4.2 Alkoxy- and Aryloxy-1,5-Naphthyridines 48

4.3 Nontautomeric 1,5-Naphthyridinones 49

4.4 1,5-Naphthyridine N-Oxides 50

Chapter 5 Thio-1,5-Naphthyridines 53

Chapter 6 Nitro-, Amino-, and Related 1,5-Naphthyridines 55

6.1 Nitro-1,5-Naphthyridines 55

6.1.1 Preparation of Nitro-1,5-Naphthyridines 55

6.1.2 Reactions of Nitro-1,5-Naphthyridines 56

6.2 Amino- and (Substituted-Amino)-1,5-Naphthyridines 57

6.2.1 Preparation of Amino-1,5-Naphthyridines 58

6.2.2 Reactions of Amino-1,5-Naphthyridines 58

Chapter 7 1,5-Naphthyridinecarboxylic Acids and Related Derivatives 61

7.1 1,5-Naphthyridinecarboxylic Acids 61

7.2 1,5-Naphthyridinecarboxylic Esters 64

7.3 1,5-Naphthyridinecarboxamides, Carbonitriles, Carbaldehydes, and Ketones 65

Chapter 8 Primary Syntheses of 1,6-Naphthyridines 67

8.1 By Condensation of Two or More Aliphatic Substrates/Synthons 67

8.2 From a Single Pyridine Substrate 69

8.3 From a Pyridine Substrate with One Synthon 75

8.3.1 Where the Synthon Supplies One Ring Atom 76

8.3.2 Where the Synthon Supplies Two Ring Atoms 78

8.3.3 Where the Synthon Supplies Three or More Ring Atoms 81

8.4 From a Pyridine Substrate with Two or More Synthons 83

8.5 From Other Heterocyclic Systems 84

Chapter 9 1,6-Naphthyridine, Alkyl-1,6-Naphthyridines, and Aryl-1,6-Naphthyridines 91

9.1 1,6-Naphthyridine 91

9.1.1 Preparation of 1,6-Naphthyridine 91

9.1.2 Properties of 1,6-Naphthyridine 93

9.1.3 Reactions of 1,6-Naphthyridines 94

9.2 Alkyl- and Aryl-1,6-Naphthyridines 97

9.2.1 Preparation of Alkyl- and Aryl-1,6-Naphthyridines 97

9.2.2 Reactions of Alkyl- and Aryl-1,6-Naphthyridines 99

Chapter 10 Halogeno-1,6-Naphthyridines 103

10.1 Preparation of Halogeno-1,6-Naphthyridines 103

10.1.1 By Direct Halogenation 103

10.1.2 By Halogenolysis of 1,6-Naphthyridinones or the Like 104

10.1.3 By Other Methods 107

10.2 Reactions of Halogeno-1,6-Naphthyridines 108

10.2.1 Alcoholysis or Phenolysis of Halogeno-1, 6-Naphthyridines 108

10.2.2 Aminolysis of Halogeno-1,6-Naphthyridines 110

10.2.3 Dehalogenation of Halogeno-1,6-Naphthyridines 111

10.2.4 Other Reactions of Halogeno-1,6-Naphthyridines 113

Chapter 11 Oxy-1,6-Naphthyridines 115

11.1 Tautomeric/Nontautomeric 1,6-Naphthyridinones and Extranuclear Hydroxy-1,6-Naphthyridines 115

11.1.1 Preparation of 1,6-Naphthyridinones and the Like 116

11.1.2 Reactions of 1,6-Naphthyridinones and the Like 118

11.2 Alkoxy- and Acyloxy-1,6-Naphthyridines 120

11.3 1,6-Naphthyridine N-Oxides 121

Chapter 12 Thio-1,6-Naphthyridines 125

Chapter 13 Nitro-, Amino-, and Related 1,6-Naphthyridines 127

13.1 Nitro-1,6-Naphthyridines 127

13.1.1 Preparation of Nitro-1,6-Naphthyridines 127

13.1.2 Reactions of Nitro-1,6-Naphthyridines 128

13.2 Amino- and (Substituted-Amino)-1,6-Naphthyridines 129

13.2.1 Preparation of Amino-1,6-Naphthyridines 130

13.2.2 Reactions of Amino-1,6-Naphthyridines 131

Chapter 14 1,6-Naphthyridinecarboxylic Acids and Related Derivatives 135

14.1 1,6-Naphthyridinecarboxylic Acids 135

14.1.1 Preparation of 1,6-Naphthyridinecarboxylic Acids 135

14.1.2 Reactions of 1,6-Naphthyridinecarboxylic Acids 137

14.2 1,6-Naphthyridinecarboxylic Esters 139

14.3 1,6-Naphthyridinecarboxamides 139

14.4 1,6-Naphthyridinecarbonitriles, Carbaldehydes, and Ketones 141

Chapter 15 Primary Syntheses of 1,7-Naphthyridines 143

15.1 From a Single Aliphatic Substrate 143

15.2 From a Single Pyridine Substrate 143

15.3 From a Pyridine Substrate with a Synthon 147

15.4 From Other Heterocyclic Systems 150

Chapter 16 1,7-Naphthyridine, Alkyl-1,7-Naphthyridines, and Aryl-1,7-Naphthyridines 153

16.1 1,7-Naphthyridine 153

16.1.1 Preparation of 1,7-Naphthyridine 153

16.1.2 Properties of 1,7-Naphthyridine 154

16.1.3 Reactions of 1,7-Naphthyridine 155

16.2 Alkyl- and Aryl-1,7-Naphthyridines 157

16.2.1 Preparation of Alkyl- and Aryl-1,7-Naphthyridines 157

16.2.2 Reactions of Alkyl- and Aryl-1,7-Naphthyridines 158

Chapter 17 Halogeno-1,7-Naphthyridines 161

17.1 Preparation of Halogeno-1,7-Naphthyridines 161

17.2 Reactions of Halogeno-1,7-Naphthyridines 163

Chapter 18 Oxy-1,7-Naphthyridines 167

18.1 1,7-Naphthyridinones 167

18.1.1 Preparation of 1,7-Naphthyridinones 167

18.1.2 Reactions of 1,7-Naphthyridinones 168

18.2 Alkoxy- and Acyloxy-1,7-Naphthyridines 170

18.3 1,7-Naphthyridine N-Oxides 171

Chapter 19 Thio-1,7-Naphthyridines 173

Chapter 20 Nitro-, Amino-, and Related 1,7-Naphthyridines 175

20.1 Nitro-1,7-Naphthyridines 175

20.2 Amino-1,7-Naphthyridines 176

Chapter 21 1,7-Naphthyridinecarboxylic Acids and Related Derivatives 179

21.1 1,7-Naphthyridinecarboxylic Acids 179

21.1.1 Preparation of 1,7-Naphthyridinecarboxylic Acids 179

21.1.2 Reactions of 1,7-Naphthyridinecarboxylic Acids 180

21.2 1,7-Naphthyridinecarboxylic Esters 182

21.3 1,7-Naphthyridinecarboxamides 182

21.4 1,7-Naphthyridinecarbonitriles 182

21.5 1,7-Naphthyridinecarbaldehydes and Ketones 182

Chapter 22 Primary Syntheses of 1,8-Naphthyridines 183

22.1 From an Aliphatic Substrate 183

22.2 From a Single Pyridine Substrate 184

22.3 From a Pyridine Substrate and Synthon(s) 187

22.4 From Other Heterocyclic Substrates 192

Chapter 23 1,8-Naphthyridine, Alkyl-1,8-Naphthyridines, and Aryl-1,8-Naphthyridines 197

23.1 1,8-Naphthyridine and Hydro Derivatives 197

23.1.1 Preparation of 1,8-Naphthyridine 197

23.1.2 Properties of 1,8-Naphthyridine 198

23.1.3 1,8-Naphthyridine Complexes 199

23.1.4 Reactions of 1,8-Naphthyridine 200

23.2 Alkyl- and Aryl-1,8-Naphthyridines 203

23.2.1 Preparation of Alkyl- and Aryl-1,8-Naphthyridines 203

23.2.2 Reactions of Alkyl- and Aryl-1,8-Naphthyridines 205

Chapter 24 Halogeno-1,8-Naphthyridines 209

24.1 Preparation of Halogeno-1,8-Naphthyridines 209

24.2 Reactions of Halogeno-1,8-Naphthyridines 214

Chapter 25 Oxy-1,8-Naphthyridines 221

25.1 1,8-Naphthyridinones and the Like 221

25.1.1 Preparation of 1,8-Naphthyridinones and the Like 221

25.1.2 Reactions of 1,8-Naphthyridinones and the Like 224

25.2 Alkoxy- and Aryloxy-1,8-Naphthyridines 227

25.3 1,8-Naphthyridine N-Oxides 228

Chapter 26 Thio-1,8-Naphthyridines 231

26.1 1,8-Naphthyridinethiones 231

26.2 Alkylthio- and Arylthio-1,8-Naphthyridines 232

26.3 1,8-Naphthyridine Sulfoxides and Sulfones 232

26.4 1,8-Naphthyridinesulfonic Acids and the Like 233

Chapter 27 Nitro-, Amino-, and Related 1,8-Naphthyridines 235

27.1 Nitro-1,8-Naphthyridines 235

27.1.1 Preparation of Nitro-1,8-Naphthyridines 235

27.1.2 Reactions of Nitro-1,8-Naphthyridines 237

27.2 Nitroso-1,8-Naphthyridines 238

27.3 Amino-1,8-Naphthyridines 238

27.3.1 Preparation of Amino-1,8-Naphthyridines 238

27.3.2 Reactions of Amino-1,8-Naphthyridines 241

Chapter 28 1,8-Naphthyridinecarboxylic Acids and Related Derivatives 247

28.1 1,8-Naphthyridinecarboxylic Acids 247

28.1.1 Preparation of 1,8-Naphthyridinecarboxylic Acids 247

28.1.2 Reactions of 1,8-Naphthyridinecarboxylic Acids 249

28.2 1,8-Naphthyridinecarbonyl Halides 251

28.3 1,8-Naphthyridinecarboxylic Esters 252

28.3.1 Preparation of 1,8-Naphthyridinecarboxylic Esters 252

28.3.2 Reactions of 1,8-Naphthyridinecarboxylic Esters 252

28.4 1,8-Naphthyridinecarboxamides 254

28.4.1 Preparation of 1,8-Naphthyridinecarboxamides 254

28.4.2 Reactions of 1,8-Naphthyridinecarboxamides 255

28.5 1,8-Naphthyridinecarbonitriles 257

28.6 1,8-Naphthyridinecarbaldehydes and Related Ketones 257

28.6.1 Preparation of the Carbaldehydes and Ketones 257

28.6.2 Reactions of the Carbaldehydes and Ketones 259

Chapter 29 The 2,6-Naphthyridines 261

29.1 Primary Syntheses of 2,6-Naphthyridines 261

29.1.1 2,6-Naphthyridines by Cyclization of Pyridine Derivatives 261

29.1.2 2,6-Naphthyridines by Cyclocondensation of a Pyridine Derivative with a Synthon 263

29.1.3 2,6-Naphthyridines from Other Heterocyclic Substrates 264

29.2 2,6-Naphthyridine and Alkyl-2,6-Naphthyridines 265

29.2.1 Preparation of 2,6-Naphthyridine 266

29.2.2 Properties of 2,6-Naphthyridine 266

29.3 Halogeno-2,6-Naphthyridines 267

29.3.1 Preparation of Halogeno-2,6-Naphthyridines 267

29.3.2 Reactions of Halogeno-2,6-Naphthyridines 268

29.4 Oxy-2,6-Naphthyridines 269

29.5 Thio-2,6-Naphthyridines 270

29.6 Nitro-, Amino-, and Related 2,6-Naphthyridines 271

29.6.1 Preparation of Amino-2,6-Naphthyridines 271

29.6.2 Reactions of Amino-2,6-Naphthyridines 272

29.7 2,6-Naphthyridinecarboxylic Acids and Related Derivatives 272

Chapter 30 The 2,7-Naphthyridines 275

30.1 Primary Syntheses of 2,7-Naphthyridines 275

30.1.1 2,7-Naphthyridines from Nonheterocyclic Precursors 275

30.1.2 2,7-Naphthyridines by Cyclization of Pyridine Substrates 277

30.1.3 2,7-Naphthyridines by Cyclocondensation of Pyridine Substrates with Synthons 278

30.1.4 2,7-Naphthyridines from Other Heterocyclic Substrates 280

30.2 2,7-Naphthyridine and Alkyl-2,7-Naphthyridines 283

30.2.1 Preparation of 2,7-Naphthyridine 283

30.2.2 Properties of 2,7-Naphthyridine 283

30.2.3 Reactions of 2,7-Naphthyridine 284

30.3 Halogeno-2,7-Naphthyridines 285

30.3.1 Preparation of Halogeno-2,7-Naphthyridines 286

30.3.2 Reactions of Halogeno-2,7-Naphthyridines 287

30.4 Oxy-2,7-Naphthyridines 289

30.5 Thio-2,7-Naphthyridines 290

30.6 Nitro-, Amino-, and Related 2,7-Naphthyridines 290

30.7 2,7-Naphthyridinecarboxylic Acids and Related Derivatives 291

30.7.1 2,7-Naphthyridinecarboxylic Acids 291

30.7.2 2,7-Naphthyridinecarboxylic Esters 292

30.7.3 2,7-Naphthyridinecarboxamides and Carbonitriles 293

30.7.4 2,7-Naphthyridinecarbaldehydes and Ketones 293

References 295

Appendix Tables of Simple Naphthyridines 337

Table A.1 Alphabetical List of Simple 1,5-Naphthyridines 339

Table A.2 Alphabetical List of Simple 1,6-Naphthyridines 348

Table A.3 Alphabetical List of Simple 1,7-Naphthyridines 361

Table A.4 Alphabetical List of Simple 1,8-Naphthyridines 366

Table A.5 Alphabetical List of Simple 2,6-Naphthyridines 409

Table A.6 Alphabetical List of Simple 2,7-Naphthyridines 411

Index 415