Table of Contents

1 Synthesis of 1,2,3-thiadiazoles 1

1.1 Cyclization of Hydrazones with Thionyl Chloride (Hurd–Mori Synthesis) 1

1.1.1 Scope and Limitations 2

1.1.2 Mechanism of the Hurd–Mori Reaction 4

1.1.3 Application of the Hurd–Mori Reaction in Organic Synthesis 5

1.2 Cycloaddition of Diazoalkanes onto a C=S bond (Pechmann Synthesis) 17

1.3 Heterocyclization of α-diazo Thiocarbonyl Compounds (Wolff Synthesis) 22

1.3.1 Introduction of a Diazo Function into Compounds Containing a C=S Bond 23

1.3.2 Introduction of a C=S Bond in the α-position to a Diazo Group 27

1.3.3 Simultaneous Introduction of Diazo and Thiocarbonyl Functions 29

1.4 Transformations of other Sulfur-containing Heterocyclic Compounds 30

1.5 Elaboration of Preformed 1,2,3-Thiadiazoles 33

1.5.1 Carboxylic Acids 33

1.5.2 Functional Derivatives of Carboxylic Acids 35

1.5.3 Aldehydes 36

1.5.4 Amino-1,2,3-Thiadiazoles 37

1.5.5 Halo Derivatives 39

1.5.6 5-Hydrazino-, 5-Mercapto-1,2,3-Thiadiazoles and 5-Sulfide Derivatives 40

1.5.7 2-(1,2,3-Thiadiazol-5-yl)acetic Acid Derivatives 41

1.5.8 Alkenyl-1,2,3-Thiadiazoles 42

1.5.9 5-Hydroxyiminomethyl- and 5-Diazomethyl-1,2,3-Thiadiazoles 42

1.5.10 4-Hydroxymethyl-1,2,3-Thiadiazoles 43

1.6 Tables 44

1.7 Selected Procedures 79

1.7.1 1,2,3-Thiadiazole-4-Carbaldehyde 79

1.7.2 4-Phenyl-1,2,3-Thiadiazole 80

1.7.3 4-Phenyl-1,2,3-Thiadiazole-5-Carbaldehyde 81

1.7.4 4-Phenyl-5-Oxyiminomethyl-1,2,3-Thiadiazole 82

1.7.5 5-Phenyl-1,2,3-Thiadiazole-4-Carbaldehyde 82

1.7.6 5-Chloro-1,2,3-Thiadiazole-4-Carbaldehyde 83

1.7.7 Ethyl 5-amino-1,2,3-Thiadiazole-4-Carboxylate 84

1.7.7.1 Pechmann Method 84

1.7.7.2 Wolff Method 85

1.7.8 Ethyl 5-chloro-1,2,3-Thiadiazole-4-Carboxylate 86

1.7.9 4-Phenyl-2-(2,4,6-Trichlorophenyl)-1,2,3-Thiadiazolium Chloride 86

1.7.10 5-Amino-4-ethoxycarbonyl-2-phenyl-1,2,3-thiadiazolium bromide 87

References 88

2 Structure of 1,2,3-Thiadiazoles 93

2.1 Theoretical Methods 93

2.2 Experimental Structural Methods 97

2.2.1 X-ray Analysis 97

2.2.2 Nuclear Magnetic Resonance Spectroscopy 103

2.2.2.1 Proton NMR Spectroscopy 103

2.2.2.2 Carbon-13 NMR Spectroscopy 103

2.2.2.3 Nitrogen-14 NMR Spectroscopy 106

2.2.2.4 Nitrogen-15 NMR Spectroscopy 106

2.2.3 Mass Spectrometry 107

2.2.4 Other Spectroscopic Data 110

References 110

3 Chemical Properties of 1,2,3-Thiadiazoles 113

3.1 Reactions due to the Reactivity of Ring Atoms 113

3.1.1 Reactions with Electrophiles 113

3.1.1.1 Protonation 113

3.1.1.2 Complexation 114

3.1.1.3 Alkylation 115

3.1.1.4 Acylation 116

3.1.1.5 Oxidation 116

3.1.1.6 Electrophilic Substitution of Hydrogen 117

3.1.2 Reactions with Nucleophiles 117

3.1.2.1 Attack at the Sulfur Atom 117

3.1.2.2 Attack at the C5 Atom 118

3.1.2.3 Attacks at H4 and H5 120

3.1.2.4 Cycloaddition Reactions 121

3.2 Reactions of Substituents 122

3.2.1 5-Alkyl-1,2,3-thiadiazoles 122

3.2.2 1,2,3-Thiadiazole-4-carbaldehyde 123

3.2.3 5-Amino-1,2,3-thiadiazole-4-carbothioamide 124

3.2.4 Mercapto-1,2,3-thiadiazoles 124

3.3 Rearrangements 124

3.3.1 Dimroth-type Rearrangements 125

3.3.2 Cornforth-type Rearrangements 129

3.3.2.1 Rearrangements of 4-(iminomethyl)- substituted-1,2,3-Thiadiazoles 129

3.3.2.2 Degenerate Rearrangements of 4-Thiocarbamoyl-1,2,3-Thiadiazoles 133

3.3.2.3 Rearrangements of 1,2,3-Thiadiazoles Bearing Diazo, Azido and Hydrazono Groups in the 5-`Position 133

3.3.2.4 Tandem Rearrangements 136

3.4 Ring Cleavage of 1,2,3-Thiadiazoles 137

3.4.1 Thermal Decomposition 137

3.4.2 Photochemical Decomposition 141

3.4.3 Base-catalyzed Decomposition 143

3.4.4 Oxidative and Reductive Processes 149

3.4.5 Other Processes for Ring Cleavage 151

References 152

4 Fused 1,2,3-Thiadiazoles 155

4.1 1,2,3-Thiadiazoles Fused with Five-Membered Rings 155

4.1.1 Cyclopenteno-1,2,3-thiadiazoles 155

4.1.2 Pyrrolo[2,3-d][1,2,3]thiadiazoles 158

4.1.3 Pyrrolo[3,2-d][1,2,3]thiadiazoles 158

4.1.4 Pyrrolo[3,4-d][1,2,3]thiadiazoles 158

4.1.5 4,6-Dihydrofurano[3,4-d][1,2,3]thiadiazoles 159

4.1.6 Thieno[2,3-d][1,2,3]thiadiazoles 159

4.1.7 Thieno[3,2-d][1,2,3]thiadiazoles 160

4.1.8 Thieno[3,4-d][1,2,3]thiadiazoles 162

4.1.9 Selenopheno[3,4-d][1,2,3]thiadiazole 162

4.1.10 Benzoselenopheno[3,2-d][1,2,3]thiadiazole 163

4.2 1,2,3-Thiadiazoles Fused with Six-Membered Rings 163

4.2.1 Cyclohexeno-1,2,3-thiadiazoles 163

4.2.2 Benzo-1,2,3-thiadiazoles 166

4.2.3 Piperidino[3,4-d][1,2,3]thiadiazoles 173

4.2.4 1,2,3-Thiadiazolo[4,5-b]pyridines 174

4.2.5 1,2,3-Thiadiazolo[4,5-c]pyridines 174

4.2.6 1,2,3-Thiadiazolo[5,4-c]pyridines 176

4.2.7 1,2,3-Thiadiazolo[5,4-d]pyrimidines 176

4.2.8 1,2,3-Thiadiazolo[4,5-d]pyrimidines 178

4.2.9 Pyrano[3,4-d][1,2,3]thiadiazole 179

4.2.10 Thiopyrano[4,3-d][1,2,3]thiadiazoles 179

4.2.11 Thiopyrano[2,1-d][1,2,3]thiadiazole 180

4.2.12 Selenopyrano[4,3-d][1,2,3]thiadiazoles 181

4.3 1,2,3-Thiadiazoles Fused with Seven-Membered Rings 181

4.3.1 Benzooxepino- and Benzothiepino[3,4-d][1,2,3]thiadiazoles 181

4.3.2 Thiadiazolo[5,4-d]benzazepines 182

4.3.3 1,2,3-Thiadiazolo[5,4-b][1,5]benzodiazepine 182

4.4 Bicyclic 1,2,3-Thiadiazoles of Azathiapentalenic Structure 183

References 188

5 Synthesis and Properties of 1,2,3-Selenadiazoles 193

5.1 Synthesis of 1,2,3-Selenadiazoles 193

5.1.1 Oxidative Cyclization of Hydrazones by Se-containing Reagents 193

5.1.2 Cycloaddition Reactions of Diazoalkanes with Compounds Containing C=Se Bonds 197

5.1.3 Elaboration of Preformed 1,2,3-Selenadiazoles 197

5.1.4 Miscellaneous Syntheses 201

5.2 Structural Data of 1,2,3-Selenadiazoles 201

5.2.1 Mass Spectrometry 201

5.2.2 Proton NMR Spectroscopy 201

5.2.3 Carbon-13 NMR Spectroscopy 202

5.2.4 Nitrogen-15 NMR Spectroscopy 202

5.2.5 Selenium-77 NMR Spectroscopy 203

5.2.6 X-ray Crystallography 203

5.2.7 Miscellaneous 204

5.3 Reactivity of 1,2,3-Selenadiazoles 204

5.3.1 Ring Cleavage 204

5.3.1.1 Thermal Reactions 204

5.3.1.2 Photochemical Reactions 210

5.3.1.3 Base-catalyzed Reactions 211

5.3.1.4 Radical-catalyzed Reactions 214

5.3.1.5 Reaction with Metal Complexes 215

5.3.1.6 Miscellaneous Ring Cleavage Reactions 217

5.3.2 Formation of Salts and Ylides 218

5.4 Fused 1,2,3-Selenadiazoles 220

5.4.1 Bicyclic 1,2,3-Selenadiazoles 220

5.4.2 Tricyclic 1,2,3-Selenadiazoles 221

5.4.3 Tetra- and Pentacyclic 1,2,3-Selenadiazoles 222

5.5 Applications of 1,2,3-Selenadiazoles 222

References 224

6 1,2,3-Thiadiazoles in Medicine and Agriculture 229

6.1 Medicine 229

6.2 Agriculture 231

6.2.1 Thidiazuron 232

6.2.2 Bion 233

References 236

Index 239

About the Author

Wim Dehaen is Professor in the Department of Chemistry at the University of Leuven. Vasiliy Bakulev is Professor in the Department of Technology for Organic Synthesis?at The Urals State Technical University.