Pyrazines, Volume 58, Supplement 1

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

"...embraces a mass of important historical material as well as a modern systematic treatment of pyrazine chemistry." (SciTech Book News, Vol. 26, No. 2, June 2002)

• Chapter 1 Primary Syntheses From Aliphatic Or Carbocyclic Synthons 11.1 From a Single Six-Atom Synthon 11.1.1 By Completion of the N—C2 Bond 11.1.1.1 From Appropriate ω-Unsaturated Azaalkylamines 11.1.1.2 From Appropriate ω-Halogeno(azaalkylamines) 21.1.1.3 From Appropriate α,ω-Diamino(azaalkanes) 21.1.1.4 From Appropriate ω-Amino(azaalkanols) 31.1.1.5 From Appropriate ω-Amino(azaalkanals) 31.1.1.6 From Appropriate ω-Amino(azaalkanones) 41.1.1.7 From Appropriate ω-Amino(azaalkanoic Acids) 61.1.1.8 From Appropriate ω-Amino(azaalkanoic Esters) 61.1.1.9 From Appropriate ω-Amino(azaalkanamides) 81.1.1.10 From Appropriate ω-Amino(azaalkanamides) 81.1.2 By Completion of the C2—C3 Bond 91.2 From Two Synthons 101.2.1 By Using a One-Atom and a Five-Atom Synthon 111.2.1.1 Where the One-Atom Synthon Supplies N1 111.2.1.2 Where the One-Atom Synthon Supplies C2 141.2.2 By Using a Two-Atom and a Four-Atom Synthon 151.2.2.1 Where the Two-Atom Synthon Supplies N1 + C2 151.2.2.2 Where the Two-Atom Synthon Supplies C2 + C3 161.2.3 By Using Two Three-Atom Synthons 291.2.3.1Where Identical Synthons Provide N1 + C2 + C3 and N4 + C5 + C6 291.2.3.2 Where Different Synthons Provide N1 + C2 + C3 and N4 + C5 + C6 341.2.3.3 Where the Synthons Provide N1 + C2 + C6 and C3 + N4 + C5 371.3 From Three Synthons 391.4 From Four or More Synthons 391.4.1 Where Synthons Provide N1, C2 + C3, N4 + C5 + C6 401.4.2 Where Synthons Provide N1 + C2, C3 + N4, C5, C6 411.4.3 Where Synthons Provide N1 + C2 + C3, N4 + C5, C6 421.5 Appendix: Glance Index to Typical Pyrazine Derivatives Available from Aliphatic or Carbocyclic Synthons 42Chapter 2 Primary Syntheses From Other Heterocyclic Systems 472.1 Pyrazines from Other Heteromonocyclic Systems 472.1.1 Azepines as Substrates 472.1.2 Azetes as Substrates 482.1.3 Azirines as Substrates 482.1.4 Azocines as Substrates 512.1.5 1,2-Diazepines as Substrates 522.1.6 1,4-Diazepines as Substrates 522.17 Furans as Substrates 522.1.8 Imidazoles as Substrates 532.1.9 Isoxazoles as Substrates 552.1.10 Oxazoles as Substrates 562.1.11 Oxirenes as Substrates 562.1.12 Pyridazines as Substrates 572.1.13 Pyridines as Substrates 572.1.14 Pyrroles as Substrates 582.1.15 l,2,5-Selenadiazoles as Substrates 582.1.16 1,2,5-Thiadiazoles as Substrates 592.1.17 Thiirenes as Substrates 592.2 Pyrazines from Heterobicyclic Systems 592.2.1 1, 2-Diazabicyclo[2.2.0]hexanes as Substrates 602.2.2 2, 4,-Diazabicyclo[3.l.0}hexanes as Substrates 6022.3 2, 3-Dioxa-5,7-diazabicyclo[2.2.2} octanes as Substrates 602.2.4 Furo[2, 3-b]pyrazines as Substrates 602.2.5 Imidazo[l, 2-a]pyrazines as Substrates 612.2.6 Indoles as Substrates 612.2.7 Isoxazolo[2,3-a]pyrazines as Substrates 622.2.8 Isoxazolo[4,5-b]pyrazines as Substrates 632.2.9 Pteridines as Substrates 6322.10 Pyrazino[2,3-d][1,3]oxazincs as Substrates 662.2.11 Pyrazino[2,3-e][l,3,4]thiadiazines as Substrates 662.2.12 Quinoxalines as Substrates 662.2.13 4-Thia-l-azabicyclo[3.2.0]heptanes as Substrates 672.2.14 [1,2,5]Thiadiazolo[3,4-b)pyrazines as Substrates 682.2.15 Thiazolo[3,2-a]pyrazines as Substrates 682.2.16 Thiazolo[3,4-a]pyrazines as Substrates 692.3 Pyrazines from Heterotricyclic Systems 692.4 Pyrazines from Spiro Heterocycles 702.5 Appendix: Glance Index to Typical Pyrazine Derivatives Available from Other Heterocyclic Systems 71Chapter 3 Pyrazine, Alkylpyrazlnes, And Arylpyrazines 753.1 Pyrazine 763.1.1 Preparation of Pyrazine 763.1.2 Properties of Pyrazine 763.1.3 Reactions of Pyrazine 773.2 C-Alkyl- and C-Arylpyrazines 793.2.1 Preparation of C-Alkyl- and C-Arylpyrazines 803.2.1.1 By Direct C-Alkylation 803.2.1.1.1 General Procedures for C-Alkylation 803.2.1.1.2 C-Alkylation in the Scböllkopf Synthesis 863.2.1.2 By Replacement of Halogeno Substituents 933.2.1.3 By Replacement of Alkoxy, Cyano, Nitro, or Oxo Substituents 1003.2.1.4 By Interconversion of Simple Alkyl Substituents 1013.2.1.5 By Elimination of Functionality from Existing Substituents. 1023.2.1.6 By Ipso-Substitution of Trimethylsiloxycarbonyl Substituents 1053.2.2 Preparation of N-Alkyl- and N-Arylpiperazines 1053.2.2.l By N-Alkylation Processes 1063.2.2.2 By Reduction of N-Acyl or N-Alkoxycarbonylpiperazines 1123.2.2.3 By Miscellaneous Routes 1133.2.3 Properties of Alkyl- and Arylpyrazines 1143.2.4 Reactions of Alkyl- and Arylpyrazines 1173.2.4.1 Oxidative Reactions 1173.2.4.2 Reductive Reactions 1193.2.4.3 Extranuclear Halogenation 1203.2.4.4 Extranuclear Alkylation 1223.2.4-.5 Extranuclear Alkylidenation 1233.2.4.6 Extranuclear Acylation or Carboxylation 1253.2.4.7 Cyclization 1263.24.8 “Ammoxidation” of Methyl to Cyano Groups 1283.2.4.9 Addition Reactions at Alkenyl or Alkynyl Substituents 1283.2.4.10 Miscellaneous Reactions 1303.3 N Alkylpyrazinium Salts and Related Ylides 1313.3.1 Preparation of N-Alkylpyrazinium Salts 1313.3.2 Reactions of N-Alkylpyrazinium Salts 132Chapter 4 Halogenopyrazines 1374.1 Preparation of Nuclear Halogenopyrazin1374.1.1 Nuclear Halogenopyrazines from Pyrazinones 1374.1.2 Nuclear Halogenopyrazines by Direct Halogenation 1414.1.3 Nuclear Halogenopyrazines by Deoxidative Halogenation of Pyrazine N-Oxides 1454.1.4 Nuclear Halogenopyrazines from Pyrazinamines 1464.1.5 Nuclear Halogenopyrazines by Transhalogenation 1484.1.6 Nuclear Halogenopyrazines via Trimethylsiloxypyrazines 1494.2 Reactions of Nuclear Halogenopyrazines 1504.2.1 Aminolysis of Nuclear Halogenopyrazines 1584.2.2 Hydrolysis of Nuclear Halogenopyrazines 1644.2.3 Alcoholysis or Phenolysis of Nuclear Halogenopyrazines 1594.2.4 Thiolysis of Nuclear Halogenopyrazines 1644.2.5 Alkanethiolysis or Arenerhiolysis of Nuclear Halogenopyrazines 1664.2.6 Azidolysis of Nuclear Halogenopyrazines 1704.2.7 Hydrogenolysis of Nuclear Halogenopyrazines 1714.2.8 Cyanolysis of Nuclear Halogenopyrazines 1734.2.9 Miscellancous Displacement Reactions of Nuclear Halogenopyrazines 1744.2.10 Fission, Rearrangement, or Cyclocondensation of Nuclear Halogenopyrazines 1764.3 Preparation of Extranuclear Halogenopyrazines 1784.3.1 Extranuclear Halogenopyrazines from Corresponding Hydroxypyrazines 1784.3.2 Extranuclear Halogenopyrazines by Minor Procedures 1804.4 Reactions of Extranuclear HalogenopyrazinesChapter 5 Oxypyrazines 1915.1 Tautomeric Pyrazinones 1915.1.1 Preparation of Tautomeric Pyrazinones 1915.1.2 Reactions of Tautomeric Pyrazinones 1915.1.2.1 Conversion into Pyrazinethiones5.1.2.2 Conversion into O- and/or N-Alkylated Derivatives 1985.1.2.3 Conversion into O- and/or N-Alkylated Derivatives 1985.1.2.4 Miscellaneous Reactions 2055.2 Extranuclear Hydroxypyrazines 2085.2.1 Preparation of Extranuclear Hydroxypyrazines 2085.2.2 Reactions of Extranuclear Hydroxypyrazines 2025.3 Nuclear and Extranuclear Alkoxy- or Aryloxypyrazines 2175.3.1 Preparation of Alkoxy- or Aryloxypyrazines 2175.3.2 Reactions of Alkoxy- or Aryloxypyrazines 2195.4 Nontautomeric Pyrazinones_and N-Alkylpyraziniumolates 2215.4.1 Preparation of Nontautomeric Pyrazinones 2215.4.2 Reactions of Nontautomeric Pyrazinones 2225.5Pyrazine N-Oxides 2255.5.1 Preparation of Pyrazine N-Oxides 2265.5.1.1 From N-Alkoxypyrazinones 2265.5.1.2 By Direct, N-Oxidation 2265.5.2 Reactions of Pyrazine N-Oxides 2305.5.2.1 Deoxygenation 2315.5.2.2 O-Alkylation or O-Acylation 2335.5.2.3 Conversion into C-Acyloxypyrazines 2345.5.2.4 Conversion into C-Amino-, C-Azido-, C-Cyano-, or C-Alkylthiopyrazines 2375.5.2.5 Miscellaneous Reactions 2385.6 Appendix: Trivial Names for Pyrazine Derivatives 240Chapter 6 Thiopyrazines 2456.1 Pyrazinethiones and Pyraz1nethiols 2456.1.1 Preparation of Pyrazinethiones and Pyrazinethiols 2456.1.2 Reactions of Pyrazinethiones and Pyrazinethiols 2486.2 Alkylthiopyrazines and Dipyrazinyl Sulfides 2516.2.1 Preparation of Alkylthiopyrazines 2516.2.2 Reactions of Alkylthiopyrazines 2526.2.2.1 Oxidation to Sulfoxides or Sulfones 2526.2.2 2 Miscellaneous Reactions 2546.3 Dipyrazinyl Disulfides and Pyrazinesulfonic Acid Derivatives 2556.4 Pyrazine Sulfoxides and Sulfones 255Chapter 7 Nitro- Amino-, And Related Pyrazies 2597.1 Nitropyrazines 2597.1.1 Preparation of Nitropyrazines 2597.1.2 Reactions of Nitropyrazines 2617.2 Nitrosopyrazines 2627.2.1 C-Nitrosopyrazines 2627.2.2 N-Nitrosopipcrazines and Related Compounds 2627.3 Regular Aminopyrazines 2657.3.1 Preparation of Regular Aminopyrazines 2657.3.2 Reactions of Regular Aminopyrazines 2737.3.2.1 N-Acylation of Aminopyrazines and Subsequent Cyclizations 2737.3.2.2 N-Alkylidenation of Aminopyrazines and Subsequent Cyclizations 2777.3.2.3 N-Alkylation of Aminopyrazines and Subsequent Cyclizations 2807.3.2.4 Conversion into Ureidopyrazines or Related Products 2827.3.2.5 Conversion into Trialkylsilylamino-, Triphenylphosphoranylideneamino-, or Dimethylsulfitnidopyrazines 2857.3.2.6 Miscellaneous Minor Reactions 2877.4 Preparation and Reactions of Hydrazinopyrazines 2907.5 Preparation, Structure, and Reactions of Azidopyrazines 2947.6 Nontautomeric Iminopyrazines 2977.7 Arylazopyrazines 298Chapter 8 Pyrazecarboxylic Acids And Related Derivatives 2998.1 Pyrazinecarboxylic Acids 2998.1.1 Preparation of Pyrazinecarboxylic Acids 2998.1.2 Reactions of Pyrazinecarboxylic Acids 3028.2 Pyrazinecarboxylic Esters 3088.2.1 Preparation of Pyrazinecarboxylic Esters 3088.2.2 Reactions of Pyrazinecarboxylic Esters 3118.3 Pyrazinecarbonyl Halides 3178.3.1 Preparation of Pyrazinecarbonyl Halides 3178.3.2 Reactions of Pyra:dnecarbonyl Halides 3188.4 Pyrazinecarboxamides, Pyrazinecarboxamidines, and Related Derivatives 3218.4.1 Preparation of Pyrazinecarboxamides and the Like 3218.4.2 Reactions of Pyrazinecarboxamides and the Like 3248.5 Pyrazinecarbohydrazides and Pyrazinecarbonyl Azides 3288.6 Pyrazinecarbonitriles 33086.1 Preparation of Pyrazinecarbonitriles 3308.6.2 Reactions of Pyrazinecarbonitriles 3408.7 Pyrazinecarbaldehydes 3368.7.1 Preparation of Pyrazinecarbaldehydes 3368.7.2 Reactions of Pyrazinecarbaldehydes 3388.8 Pyrazine Ketones 3408.8.1 Preparation of Pyrazine Ketones 3418.8.2 Reactions of Pyrazine Ketones 3438.9 Pyrazine Cyanates, Isocyanates, Thiocyanates, Isothiocyanates, and Carbonitrile Oxides 349 Appendix: Table Of Simple Pyrazines 349References 461Index 515