Quinoxalines: Supplement Ii, Chemistry Of Heterocyclic Compounds, Volume 61

This volume in the Chemistry of Heterocyclic Compounds series presents a comprehensive review of the quinoxaline literature from 1975 to the present (2002), updating Volumes 5 and 35. It provides an alphabetical table of known simple quinoxalines, including new compounds discussed in this volume and their physical data, as well as the pyrazines from the original volumes. Biological activities, spectral or other physical studies, and other such materials appear at appropriate points in the text. The in-depth coverage includes synthesis, reactions, spectroscopic, and physical properties for each class of compounds.

Chemistry of Heterocyclic Compounds, Volume 61: Supplement II provides the most up-to-date summation of knowledge of the synthetic chemistry of quinoxalines.

Desmond J. Brown is Professor of Chemistry at The Australian National University.

CHAPTER 1: PRIMARY SYNTHESES.

1.1 From a Single Benzene Substrate.

1.1.1 By Formation of the N1, C8a Bond.

1.1.2 By Formation of the N1, C2 Bond.

1.1.2.1 Cyclization of o-(Ethylamino)aniline Derivatives.

1.1.2.2 Direct Cyclization of o-(Ethylamino)nitrobenzene Derivatives.

1.1.2.3 Reductive Cyclization of o-(Ethylamino)nitrobenzene Derivatives.

1.1.3 By Formation of the C2, C3 Bond.

1.2 From a Benzene Substrate with an Ancillary Synthon.

1.2.1 When the Synthon Supplies N1 of the Quinoxaline.

1.2.2 When the Synthon Supplies C2 of the Quinoxaline.

1.2.3 When the Synthon Supplies C2 + C3 of the Quinoxaline.

1.2.3.1 Using a Dialdehyde (Glyoxal) or Related Synthon.

1.2.3.2 Using an Aldehydo Ketone or Related Synthon.

1.2.3.3 Using an Aldehydo Acid or Related Synthon.

1.2.3.4 Using an Aldehydo Ester or Related Synthon.

1.2.3.5 Using an Aldehydo Amide, Nitrile, Acyl Halide, or Related Synthon.

1.2.3.6 Using a Diketone or Related Synthon.

1.2.3.7 Using a Keto Acid or Related Synthon.

1.2.3.8 Using a Keto Ester or Related Synthon.

1.2.3.9 Using a Keto Amide, Nitrile, Acyl Halide, or Related Synthon.

1.2.3.10 Using a Diacid (Oxalic Acid) as Synthon.

1.2.3.11 Using a Diester (a Dialkyl Oxalate) or Related Synthon.

1.2.3.12 Using an Estero Amide, Nitrile, Acyl Halide, or Related Synthon.

1.2.3.13 Using a Diamide (Oxamide), Amido Nitrile, or Related Synthon.

1.2.3.14 Using a Diacyl Dihalide (Oxalyl Halide) or Related Synthon.

1.2.4 When the Synthon Supplies N1 + C2 + C3 of the Quinoxaline.

1.2.5 When the Synthon Supplies N1 + C2 + C3 + N4 of the Quinoxaline.

1.3 From a Benzene Substrate with Two or More Synthons.

1.4 From a Pyrazine Substrate with or without Synthon(s).

1.5 From Other Heteromonocyclic Substrates/Synthons.

1.5.1 Azirines as Substrates/Synthons.

1.5.2 1,2,3-Dithiazol-1-iums as Substrates/Synthons.

1.5.3 Furans as Substrates/Synthons.

1.5.4 Isothiazoles as Substrates/Synthons.

1.5.5 Isoxazoles as Substrates/Synthons.

1.5.6 Oxazoles as Substrates/Synthons.

1.5.7 Oxirenes as Substrates/Synthons.

1.5.8 Pyrans as Substrates/Synthons.

1.5.9 Pyridazines as Substrates/Synthons.

1.5.10 Pyridines as Substrates/Synthons.

1.5.11 Pyrimidines as Substrates/Synthons.

1.5.12 Pyrroles as Substrates/Synthons.

1.5.13 Thiophenes as Substrates/Synthons.

1.5.14 1,2,4-Triazines as Substrates/Synthons.

1.5.15 1,2,3-Triazoles as Substrates/Synthons.

1.6 From Heterobicyclic Substrates/Synthons.

1.6.1 7-Azabicyclo[4.1.0]heptanes as Substrates/Synthons.

1.6.2 Benzimidazoles as Substrates/Synthons.

1.6.3 1,4-Benzodiazepines as Substrates/Synthons.

1.6.4 1,5-Benzodiazepines as Substrates/Synthons.

1.6.5 1-Benzopyrans (Chromenes) as Substrates/Synthons.

1.6.6 2,1,3-Benzoselena(or thia)diazoles as Substrates/Synthons.

1.6.7 2,1,3-Benzoxadiazoles as Substrates/Synthons.

1.6.8 Cycloheptapyrazines as Substrates/Synthons.

1.6.9 Indoles as Substrates/Synthons.

1.6.10 Pyrrolo[3,4-b]pyrazines as Substrates/Synthons.

1.7 From Heteropolycyclic Substrates/Synthons.

1.7.1 Azeto- or Azirino[1,2-a]quinoxalines as Substrates/Synthons.

1.7.2 Benz[g]indoles as Substrates/Synthons.

1.7.3 Benzo[3,4]cyclobuta[1,2-b]quinoxalines as Substrates/Synthons.

1.7.4 Benzo[g]pteridines as Substrates/Synthons.

1.7.5 [1]Benzopyrano[2,3-b]quinoxalines as Substrates/Synthons.

1.7.6 [1]Benzothiopyrano[4,3-b]pyrroles as Substrates/Synthons.

1.7.7 Cyclobuta[b]quinoxalines as Substrates/Synthons.

1.7.8 1,3-Dithiolo[4,5-b]quinoxalines as Substrates/Synthons.

1.7.9 1,4-Ethanoquinoxalines as Substrates/Synthons.

1.7.10 Furo[2,3-b]quinoxalines as Substrates/Synthons.

1.7.11 Furo[3,4-b]quinoxalines as Substrates/Synthons.

1.7.12 Indeno[1,2-b]pyrroles as Substrates/Synthons.

1.7.13 Isoxazolo[2,3-d][1,4]benzodiazepines as Substrates/Synthons.

1.7.14 Isoxazolo[2,3-a]quinoxalines as Substrates/Synthons.

1.7.15 [1,3,4]Oxadiazino[5,6-b]quinoxalines as Substrates/Synthons.

1.7.16 [1,2,4]Oxadiazolo[2,3-a]quinoxalines as Substrates/Synthons.

1.7.17 [1,2,5]Oxadiazolo[3,4-f]quinoxalines as Substrates/Synthons.

1.7.18 Phenazines as Substrates/Synthons.

1.7.19 Pyrazolo[3,4-b]quinoxalines as Substrates/Synthons.

1.7.20 Pyridazino[4,5-b]quinoxalines as Substrates/Synthons.

1.7.21 Pyrrolo[3,4-b]quinoxalines as Substrates/Synthons.

1.7.22 Quinoxalino[2,3-b]quinoxalines as Substrates/Synthons.

1.7.23 Thiazolo[2,3-b]benzothiazoliums as Substrates/Synthons.

1.7.24 Thiazolo[3,2-a]quinoxaliniums as Substrates/Synthons.

1.8 From Spiro Heterocyclic Substrates.

1.9 Glance Index to Typical Quinoxaline Derivatives Available by Primary Syntheses.

CHAPTER 2: QUINOXALINE, ALKYLQUINOXALINES, AND ARYLQUINOXALINES.

2.1 Quinoxaline.

2.1.1 Preparation of Quinoxaline.

2.1.2 Properties of Quinoxaline.

2.1.3 Reactions of Quinoxaline.

2.2 Alkyl- and Arylquinoxalines.

2.2.1 Preparation of C-Alkyl- and C-Arylquinoxalines.

2.2.1.1 By Direct Alkylation or Arylation.

2.2.1.2 By Alkanelysis or Arenelysis of Halogenoquinoxalines.

2.2.1.3 From C-Formyl-, C-Aroyl-, C-Cyano-, or Oxoquinoxalines.

2.2.1.4 By Interconversion of Alkyl or Aryl Substituents.

2.2.1.5 By Elimination of Functionality from Substituted-Alkyl Substituents.

2.2.2 Preparation of N-Alkyl or N-Aryl Derivatives of Hydroquinoxalines.

2.2.3 Properties of Alkyl- and Arylquinoxalines.

2.2.4 Reactions of Alkyl- and Arylquinoxalines.

2.3 N-Alkylquinoxalinium Salts.

2.3.1 Preparation of N-Alkylquinoxalinium Salts.

2.3.2 Reactions of N-Alkylquinoxalinium Salts.

CHAPTER 3 HALOGENOQUINOXALINES.

3.1 Preparation of Nuclear Halogenoquinoxalines.

3.1.1 Nuclear Halogenoquinoxalines from Quinoxalinones.

3.1.2 Nuclear Halogenoquinoxalines by Direct Halogenation.

3.1.3 Nuclear Halogenoquinoxalines from Quinoxalinamines.

3.1.4 Nuclear Halogenoquinoxalines by Transhalogenation.

3.1.5 Nuclear Halogenoquinoxalines from Miscellaneous Substrates.

3.2 Reactions of Nuclear Halogenoquinoxalines.

3.2.1 Aminolysis of Nuclear Halogenoquinoxalines.

3.2.2 Hydrolysis, Alcoholysis, or Phenolysis of Nuclear Halogenoquinoxalines.

3.2.3 Thiolysis, Alkanethiolysis, Arenethiolysis, or Arenesulfinolysis of Nuclear Halogenoquinoxalines.

3.2.4 Azidolysis of Nuclear Halogenoquinoxalines.

3.2.5 Cyanolysis of Nuclear Halogenoquinoxalines.

3.2.6 Hydrogenolysis of Nuclear Halogenoquinoxalines.

3.2.7 Other Displacement Reactions of Nuclear Halogenoquinoxalines.

3.2.8 Cyclization Reactions of Nuclear Halogenoquinoxalines.

3.3 Preparation of Extranuclear Halogenoquinoxalines.

3.4 Reactions of Extranuclear Halogenoquinoxalines.

3.4.1 Aminolysis of Extranuclear Halogenoquinoxalines.

3.4.2 Hydrolysis, Alcoholysis, or Phenolysis of Extranuclear Halogenoquinoxalines.

3.4.3 Acyloxy Derivatives from Extranuclear Halogenoquinoxalines.

3.4.4 Thiolysis, Alkanethiolysis, Arenethiolysis, or Arenesulfinolysis of Extranuclear Halogenoquinoxalines.

3.4.5 Other Displacement Reactions of Extranuclear Halogenoquinoxalines.

3.4.6 Cyclization Reactions of Extranuclear Halogenoquinoxalines.

CHAPTER 4: OXYQUINOXALINES.

4.1 Tautomeric Quinoxalinones.

4.1.1 Preparation of Tautomeric Quinoxalinones.

4.1.2 Reactions of Tautomeric Quinoxalinones.

4.1.2.1 Conversion into Quinoxalinethiones.

4.1.2.2 Conversion into O- and/or N-Alkylated Derivatives.

4.1.2.3 Miscellaneous Reactions.

4.2 Quinoxalinequinones.

4.2.1 Preparation of Quinoxalinequinones.

4.2.2 Reactions of Quinoxalinequinones.

4.3 Extranuclear Hydroxyquinoxalines.

4.3.1 Preparation of Extranuclear Hydroxyquinoxalines.

4.3.2 Reactions of Extranuclear Hydroxyquinoxalines.

4.4 Alkoxy- and Aryloxyquinoxalines.

4.4.1 Preparation of Alkoxy- and Aryloxyquinoxalines.

4.4.2 Reactions of Alkoxy- and Aryloxyquinoxalines.

4.5 Nontautomeric Quinoxalinones.

4.5.1 Preparation of Nontautomeric Quinoxalinones.

4.5.2 Reactions of Nontautomeric Quinoxalinones.

4.6 Quinoxaline N-Oxides.

4.6.1 Preparation of Quinoxaline N-Oxides.

4.6.2 Reactions of Quinoxaline N-Oxides.

4.6.2.1 Deoxygenation.

4.6.2.2 Deoxidative C-Substitutions.

4.6.2.3 Other Reactions.

CHAPTER 5: THIOQUINOXALINES.

5.1 Quinoxalinethiones and Quinoxalinethiols.

5.1.1 Preparation of Quinoxalinethiones and Quinoxalinethiols.

5.1.2 Reactions of Quinoxalinethiones and Quinoxalinethiols.

5.2 Alkylthioquinoxalines and Diquinoxalinyl Sulfides.

5.2.1 Preparation of Alkylthioquinoxalines.

5.2.2 Reactions of Alkylthioquinoxalines.

5.3 Diquinoxalinyl Disulfides and Quinoxalinesulfonic Acid Derivatives.

5.4 Quinoxaline Sulfoxides and Sulfones.

CHAPTER 6: NITRO-, AMINO-, AND RELATED QUINOXALINES.

6.1 Nitroquinoxalines.

6.1.1 Preparation of Nitroquinoxalines.

6.1.1.1 By Direct Nitration.

6.1.1.2 From Dimethylsulfimidoquinoxalines.

6.1.2 Reactions of Nitroquinoxalines.

6.1.2.1 Reduction to Quinoxalinamines.

6.1.2.2 Displacement Reactions.

6.2 Nitrosoquinoxalines.

6.3 Regular Aminoquinoxalines.

6.3.1 Preparation of Regular Aminoquinoxalines.

6.3.2 Reactions of Regular Aminoquinoxalines.

6.3.2.1 N-Acylation of Aminoquinoxalines or Reduced Quinoxalines.

6.3.2.2 N-Alkylation or Alkylidenation of Aminoquinoxalines.

6.3.2.3 Reactions Involving Initial Diazotization of Aminoquinoxalines.

6.3.2.4 Miscellaneous Transformations of Aminoquinoxalines.

6.3.2.5 Cyclization of Aminoquinoxalines.

6.4 Hydrazino- and Hydrazonoquinoxalines.

6.4.1 Preparation of Hydrazino- and Hydrazonoquinoxalines.

6.4.2 Reactions of Hydrazino- and Hydrazonoquinoxalines.

6.4.2.1 Noncyclization Reactions.

6.4.2.2 Cyclization Reactions.

6.5 Azidoquinoxalines.

6.6 Arylazoquinoxalines.

CHAPTER 7: QUINOXALINECARBOXYLIC ACIDS AND RELATED DERIVATIVES.

7.1 Quinoxalinecarboxylic Acids and Anhydrides.

7.1.1 Preparation of Quinoxalinecarboxylic Acids.

7.1.2 Reactions of Quinoxalinecarboxylic Acids.

7.2 Quinoxalinecarboxylic Esters.

7.2.1 Preparation of Quinoxalinecarboxylic Esters.

7.2.2 Reactions of Quinoxalinecarboxylic Esters.

7.3 Quinoxalinecarbonyl Halides.

7.4 Quinoxalinecarboxamides and Related Derivatives.

7.4.1 Preparation of Quinoxalinecarboxamides and the Like.

7.4.2 Reactions of Quinoxalinecarboxamides and the Like.

7.5 Quinoxalinecarbonitriles.

7.5.1 Preparation of Quinoxalinecarbonitriles.

7.5.2 Reactions of Quinoxalinecarbonitriles.

7.6 Quinoxalinecarbaldehydes.

7.6.1 Preparation of Quinoxalinecarbaldehydes.

7.6.2 Reactions of Quinoxalinecarbaldehydes.

7.7 Quinoxaline Ketones.

7.7.1 Preparation of Quinoxaline Ketones.

7.7.2 Reactions of Quinoxaline Ketones.

7.8 Quinoxaline Cyanates, Isocyanates, Thiocyanates, Isothiocyanates, and Nitrones.

APPENDIX: TABLE OF SIMPLE QUINOXALINES.

REFERENCES.

INDEX.