《FIVE-AND SIX-MEMBERED COMPOUNDS WITH NITROGEN AND OXYGEN》

Part ⅠIsoxazoles and Related Compounds＆By Adolfo Quilico1

Introduction1

Nomenclature and Numbering System3

Chapter Ⅰ．Isoxazoles5

Ⅰ．Methods of Preparation of Isoxazoles5

A．Synthesis from 1,3-Dicarbonyl Compounds and Hydroxylamine6

B．Synthesis from α-Acetylenic Ketones and Aldehydes with Hy-droxylamine14

C．Synthesis from Halogenated α,β-Ethylenic Aldehydes or Ke-tones and Hydroxylamine16

D．Isoxazoles from α,β-Unsaturated Ketones and Hydroxylamine16

E．Synthesis from α,β-Dihaloketones and Hydroxylamine16

F．Synthesis from Hydroxamyl Chlorides18

G．Synthesis from Nitrile Oxides19

H．Synthesis with Fulminic Acid and Acetylenic Derivatives22

I．Synthesis from Acetylenic Derivatives and Nitrolic Acids23

J．Synthesis from Primary Nitroparaffins,Nitrostilbenes,and Re-lated Compounds24

K．Synthesis from Unsaturated Compounds and Nitric(Nitrous)Acid27

L．Isoxazoles from Isoxazolines32

M．Other Isoxazole Syntheses33

N．Isoxazoles from Other Heterocycles34

Ⅱ．The Chemical Behavior of Isoxazoles41

A．Basic Properties41

B．Action of Reducing Agents42

C．Oxidation43

D．Action of Alkali,Alkaline Alkoxides,and Other Basic Reagents44

E．Action of Ammonia,Hydroxylamine,Hydrazine,Aromatic Amines,and Hydrazines48

F．Action of Halogens49

G．Action of Chlorosulfonic Acid49

H．Action of Nitric Acid and Mixed Acids50

I．Action of Grignard Reagent50

J．Action of Alkyl Iodides and Sulfates50

Ⅲ．Isoxazole and Its Alkyl and Aryl Derivatives53

A．Isoxazole53

B．Methylisoxazoles54

C．Homologous Alkyl-and Alkenylisoxazoles56

D．Phenylisoxazoles57

E．Homologous Aryl-and Alkylarylisoxazoles59

F．Isoxazoles Containing Heterocyclic Substituents62

Ⅳ．Isoxazole Derivatives66

A．Halogen Derivatives66

B．Nitro Derivatives67

C．Sulfonic Acids70

D．Alcohols,Glycols,and Ethers71

E．Amines73

F．Isoxazoles with Other Nitrogen-Containing Functions75

G．Aldehydes77

H．Ketones79

I．Carboxylic Acids82

J．Amino Acids88

Chapter Ⅱ．Isoxazolines95

Ⅰ．Methods of Preparation of Isoxazolines95

A．From α,β-Unsaturated Ketones and Hydroxylamine96

B．From β-Chloroketones and Hydroxylamine99

C．From Ethylenic Derivatives and Nitrile Oxides99

D．From Isoxazoline N-Oxides102

E．From Quaternary Salts102

Ⅱ．The Chemical Behavior of Isoxazolines102

Ⅲ．Substituted Isoxazolines104

A．Halo Derivatives104

B．Hydroxy Derivatives105

C．Alcohols,Aldehydes,and Ketones105

D．Carboxylic Acids105

E．Stereochemistry of 2-Isoxazolines105

Ⅳ．Isoxazoline N-Oxides111

A．Methods of Preparation111

B．Chemical Behavior of Isoxazoline N-Oxides113

Ⅴ．4,5-Dioxoisoxazolines115

Chapter Ⅲ．Isoxazolones117

Ⅰ．Methods of Preparation of 5-Isoxazolones118

A．Synthesis from β-Ketonic Esters and Hydroxylamine118

B．Synthesis from α-Acetylenic Esters and Hydroxylamine119

C．Synthesis from α,β-Unsaturated Esters and Hydroxylaminc119

D．Synthesis from Sulfur Derivatives of β-Ketonic Esters and Hy-droxylamine119

E．Synthesis with Hydroxamyl Chlorides and Nitrile Oxides120

F．Synthesis from β-Ketonic or α-Acetylenic Esters and Aldoximes121

G．Synthesis from β-Ketonic and α-Acetylenic Nitriles,and Hy-droxylamine121

H．Other Isoxazolone Syntheses121

Ⅱ．The Chemical Behavior of 5-Isoxazolones124

A．Acidic Properties124

B．Action of Reducing Agents126

C．Action of Oxidants126

D．Hydrolytic Cleavage of the Isoxazolone Ring127

E．Action of Halogens127

F．Action of Nitrous Acid128

G．Condensation Reaction with Compounds Containing Carbonyl or Dichloromethyl Groups128

H．Condensation Reactions with Aromatic Nitroso Bases129

I．Coupling with Diazonium Salts129

J．Reactions with Hydrazine Derivatives,Hydroxylamine,and Formamidines130

K．Action of Grignard Reagents130

L．Condensation with Ortho Esters130

Ⅲ．5-Isoxazolones and Their Derivatives132

A．Alkyl-and Aryl-5-lsoxazolones132

B．Unsaturated Isoxazolones132

C．Haloisoxazolones134

D．5-Iminoisoxazolones135

E．Isonitrosoisoxazolones138

F．Nitroisoxazolones139

G．Isoxazolone Azomethines139

H．Azo Derivatives140

I．Alcohols,Aldehydes,Ketones,and Carboxylic Acids of 5-Iso-xazolones142

J．Arylaminomethyleneisoxazolones145

Ⅳ．4-Isoxazolones149

Ⅴ．3-Isoxazolones151

Chapter Ⅳ．Polynuclear Isoxazole Types153

Ⅰ．Biisoxazoles153

A．Synthesis of Biisoxazoles153

B．Properties and Chemical Behavior of Biisoxazoles157

Ⅱ．Biisoxazolines158

Ⅲ．Triisoxazoles and Polyisoxazoles158

Ⅳ．Benzisoxazoles159

A．Indoxazenes160

B．Anthranils166

Ⅴ．Other Polynuclear Condensed Isoxazoles173

A．Naphthoisoxazoles173

B．Anthracene and Anthraquinone Isoxazoles174

C．Other Polynuclear Types175

Chapter Ⅴ．The Physico-Chemical Properties of Isoxazole and Its De-rivatives＆By Giovanni Speroni177

Ⅰ．Isoxazole,Alkyl-and Arylisoxazoles177

Ⅱ．Isoxazolecarboxylic Acids198

Ⅲ．Hydroxyisoxazoles and Isoxazoleamines(Isoxazolones and Isoxa-zolonimides)206

Ⅳ．Benzisoxazoles213

Chapter Ⅵ．Applications of Isoxazole Derivatives223

Ⅰ．Isoxazole Derivatives of Pharmacological Significance223

A．Analeptics223

B．Sulfa Drugs225

C．Other Isoxazole Drugs225

Ⅱ．Other Applications of Isoxazole Derivatives227

Chapter Ⅶ．Isoxazolidines229

Ⅰ．Isoxazolidines229

Ⅱ．Isoxazolidones230

Part ⅡOxadiazoles and Related Compounds＆By Lyell C．Behr233

Chapter Ⅷ．1,2,3-Oxadiazoles235

Ⅰ．The Aliphatic Diazo Compounds235

Ⅱ．The＂Diazophenols＂237

Ⅲ．The Sydnones240

Chapter Ⅸ．1,2,4-Oxadiazoles245

Ⅰ．General245

Ⅱ．Alkyl and Aryl Derivatives245

Ⅲ．Carboxylic Acids and Their Derivatives252

Ⅳ．Alcohols253

Ⅴ．Amino Compounds253

Ⅵ．Hydroxyl Derivatives255

Ⅶ．Acetonyl Compounds257

Ⅷ．Oxadiazolines(Hydrazoximes)258

Ⅸ．Oxadiazolidines259

Chapter Ⅹ．1,3,4-Oxadiazoles263

Ⅰ．General263

Ⅱ．Aryl-1,3,4-oxadiazoles263

Ⅲ．Dialkyl-1,3,4-oxadiazoles264

Ⅳ．Diaryl-and Arylalkyl-l,3,4-oxadiazoles265

Ⅴ．＂Cyclic Azo Compounds＂269

Ⅵ．Amino-l,3,4-oxadiazoles271

Ⅶ．1,3,4-Oxadiazoles with Sulfur-Containing Substituents272

Ⅷ．1,3,4-Oxadiazolines274

Ⅸ．1,3,4-Oxadiazolones274

Ⅹ．Condensed Systems277

Ⅺ．Applications of 1,3,4-Oxadiazoles278

Chapter Ⅺ．Furazans283

Ⅰ．General283

Ⅱ．Furazans284

A．The Dialkylfurazans284

B．Arylfurazans285

C．Diaryl-and Arylalkylfurazans285

D．Hydroxyfurazans287

E．Furazan Ketones287

F．Furazancarboxylic Acids289

G．Aminofurazans291

H．Condensed Furazans292

Ⅲ．Furoxans295

A．Structure295

B．Monosubstituted Furoxans298

C．Dialkylfuroxans298

D．Diaryl-and Arylalkylfuroxans299

E．Carbonyl Compounds302

F．Furoxancarboxylic Acids303

G．Other Substituted Furoxans305

H．Condensed Fuorxans305

Ⅳ．Fulminic Acid Derivatives309

Chapter Ⅻ．Dioxazoles,Dioxadiazoles,and Oxatriazoles321

Ⅰ．Dioxazoles321

Ⅱ．Dioxadiazoles322

Ⅲ．Oxatriazoles323

Part ⅢOxazines and Related Compounds＆By R．L．McKee327

Chapter ⅩⅢ．The 1,2-Oxazines329

Ⅰ．Monocyclic Systems329

Ⅱ．Condensed 1,2-Oxazine Systems335

A．Derivatives of 2,3,1H-Benzoxazine335

B．Derivatives of 1,2,4H-Benzoxazine338

C．Derivatives of Naphth[1,8-de][1,2]oxazine338

D．Derivatives of 3H-Phenanthr[9,10-d][1,2]oxazine339

E．Furazano[3,4-d][1,2]oxazine339

Chapter ⅩⅣ．The 1,3-Oxazines341

Ⅰ．Monocyclic Systems341

Ⅱ．Condensed Systems350

A．1,3-Benzoxazines351

B．3,1-Benzoxazines359

C．Pyrido[1,2-b][1,3]oxazine366

D．2-Naphth[2,3-e][1,3]oxazine366

E．4-Naphth[2,3-d][1,3]oxazine366

F．2-Naphth[2,1-e][1,3]oxazine and 1-Naphth[1,2-e][1,3]oxazine366

G．4-Naphth[1,2-d][1,3]oxazine366

H．1-Naphth[2,1-d][1,3]oxazine366

I．Naphth[1,8][1,3]oxazine367

J．4H-Anthr[1,2-d][1,3]oxazine367

K．Naphthaceno[5,6-de][1,3]oxazine367

L．2-Pyrido[3,2-h][1,3]benzoxazine367

M．4-Pyrido[2,3-h][3,1]benzoxazine367

N．Thianaphthenooxazines368

O．5-Isoindolo[2．1-a][3,1]berzoxazine368

P．Pyrazolobenzoxazines368

Q．Pyrazolo[4,3-e][1,3]oxazine369

R．Isoxazolo[4,5-e][1,3]oxazine369

S．Indazolylbenzoic Acid369

T．Indolo[3,2-d][1,3]oxazine or Indolo[2,3-d][1,3]oxazinc370

U．3,4-[Indolo(1,2)]-5,6[indolo(3,2)]-△5-dihydro-1,3-oxazine370

V．4H,5H-Pyrano[3,4-e][1,3]oxazine370

W．1,3-Oxazino[2,3-e]pyrazole371

Chapter ⅩⅤ．The 1,4-Oxazlnes377

Ⅰ．Monocyclic Systems377

Ⅱ．Condensed Systems394

A．1,4-Benzoxazines394

B．5,8-Methano-1,4-benzoxazine397

C．8-Oxa-3-azabicyclo[3,2,1]octane397

D．3-Oxa-8-azabicyclo[3,2,1]octane(Morphopyrrolidine)and 3-Oxa-9-azabicyclo[3,3,1]nonane(Morphopiperidine)398

E．Cyclopenta[b][1,4]benzoxzzine398

F．4H-Naphth[2,3][1,4]oxazine398

G．1H-Naphth[2,1][1,4]oxazine399

H．2H-Naphth[1,2][1,4]oxazine399

I．1H-Anthr[2,1][1,4]oxazine400

J．12H-Acenaphtho[1,2-b][1,4]benzoxazine400

K．3-Methyl-6,8-dioxa-3-azabicyclo[3,2,1]octane400

L．3-Oxa-6-thi-8-azabicyclo[3,2,1]octane400

M．Thiazolooxazines401

N．1H-Pyrrolo[2,1-c][1,4]oxazine401

O．Pyrrolo[3,4-b][1,4]oxazine401

P．Pyrazolo[3,4-b][1,4]oxazine401

Q．5H-[1,4]-Oxazino[2,3-d]pyrimidine402

R．Triazolobenzoxazine402

S．Imidazo[b][1,4]benzoxazine402

T．Imidazo[f][1,4]benzoxazine402

U．5H-Pyrido[1,2,3-de][l,4]benzoxazine403

V．Pyrido[3,2-b][1,4]benzoxazine,Pyrido[4,3-b][1,4]benzoxazinc and Pyrido[3,4-b][1,4]benzoxazine403

W．2H-[1,4]-Oxazino[b]phenazine403

X．7H-[1,4]-Oxazino[de]phenazine403

Y．[1,4]Benzoxazino[3,2-b][1,4]benzoxazine(Diphendioxazine)404

Z．11H-Quinoxalo[2,3-b][1,4]benzoxazine(Diphenazineoxazine)404

A′．5H-6-Oxa-12,14-dithia-5,7,13-triazapentacene(Dibenzothi-azoxine)404

B′．1H-[1,4]-Oxazino[4,3-a]indole404

C′．Pyrimidino[4,5-b][1,4]benzoxazine405

Ⅲ．Condensed Systems-Phenoxazines and Allied Compounds407

A．Phenoxazines408

B．Phenoxazones,Phenoxazines,and their Salts:the Phenoxa-zonium and Phenazoxonium Compounds414

C．Triphendioxazine and Related Compounds432

D．Trinaphthodioxazine434

E．Quinoxalo[2,3-b]phenoxazines,triphenazineoxazincs434

F．7H-Benzo[a][1,4]benzoxazino[3,2-i]phenazine435

G．Pyrido[3,2-a]phenazoxonium Salts435

H．Chrysophenoxazine435

Chapter ⅩⅥ．Systems of Two Oxygen Atoms and One Nitrogen Atom:the Dioxazines443

Ⅰ．Monocyclic Systems443

Ⅱ．Condensed Systems444

Chapter ⅩⅦ．Systems of Three Oxygen Atoms and One Nitrogen Atom445

Ⅰ．Monocyclic Systems445

Ⅱ．Condensed Systems445

Chapter ⅩⅧ．Systems of One Oxygen Atom and Two Nitrogen Atoms:the Oxadiazines447

Ⅰ．Monocyclic Systems447

A．1,2,4,4H-and 1,2,4,6H-Oxadiazines447

B．1,2,5-Oxadiazines448

C．1,2,6-Oxadiazines449

D．1,3,4-Oxadiazines450

E．1,3,5-Oxadiazines452

Ⅱ．Condensed Systems454

A．The Benzoxadiazines454

B．1H-Anthr[2,3][1,3,4]oxadiazine456

C．2H-Phenanthr[9,10][1,3,4]oxadiazine456

D．8H-Acenaphth[1,2][1,3,4]oxadiazine456

E．1,3,4-Oxadiazino[6,5-b]indole456

F．Benzopyrano-oxadiazines457

G．Anhydride of 7,9-Bis-hydroxymethyleneuric Acid457

H．5H-Pyrazolo[3,2-c][2,1,4]benzoxadiazine457

I．Pyrid[1,2-c][1,3,5]oxadiazine458

Chapter ⅩⅨ．Systems of One Oxygen Atom and Three Nitrogen Atoms459

Ⅰ．Monocyclic Systems459

Ⅱ．Condensed Systems460

Chapter ⅩⅩ．Systems of Two Oxygen Atoms and Two Nitrogen Atoms461

Ⅰ．Monocyclic Systems461

Ⅱ．Condensed Systems461

Chapter ⅩⅪ．Systems of More Than Four Hetero Atoms,Nitrogen and Oxygen463

Subject Index467