Best Synthetic Methods: Organophosphorus (V) Chemistry provides systematic coverage of the most common classes of pentavalent organophosphorus compounds and reagents (including phosphonyl, phosphoryl, and organophosphates), and allows researchers an easy point of entry into this complex and economically important field. The book follows the Best Synthetic Methods format, containing practical methods, synthetic tips, and shortcuts. Where relevant, articles include toxicity data and historical context for the reactions. Typical analytical and spectroscopic data are also presented to enable scientists to identify key compound characteristics.
The book is a valuable companion to research chemists in both academia and industry, summarizing the best practical methods (often originating in difficult-to-access, foreign-language primary literature) in one place. It is ideally suited for those working on industrial applications of these compounds, including insecticides, herbicides, flame retardants, and plasticizers.

Contributors xi

Preface xiii

1. General Overview 1

1.1. Introduction 1

1.2. Natural Occurrence of Phosphorus 1

1.3. Principal Compounds of Phosphorus 2

1.4. Phosphorus Compounds in Living Systems 4

1.5. A Brief History of Synthetic Organophosphorus Chemistry 12

1.6. Nomenclature of Organophosphorus Compounds 19

1.7. Chiral Phosphorus Compounds and Biological Implications 24

1.8. Phosphorus-Containing Pharmaceuticals 26

1.9. Fire Retardants and Fire-Extinguishing Compounds 32

1.10. Toxicology and Medical Treatment of organophosphorus Compounds 33

1.11. Fluorogenic Nerve Agent Mimics for Screening for Improved Bioscavengers 63

1.12. Biotinylated Nerve Agent Mimics for Activity-Based Enzyme Profiling 64

1.13. Working Safely with Organophosphorus Compounds 65

References 67

2. Phosphonyl Compounds 91

2.1. Introduction 91

2.2. Alkyl Alkyl-H-Phosphinates R(R′O)P(O)H 92

2.3. Alkylphosphonic Dichlorides RP(O)Cl2 96

2.4. Alkylphosphonic Dibromides RP(O)Br2 126

2.5. Alkylphosphonic Difluorides RP(O)F2 128

2.6. Alkylphosphonofluoridic Acids RP(O)(OH)F 131

2.7. Alkylphosphonic Chlorofluorides RP(O)CIF 136

2.8. Alkylphosphonic Isocyanatofluorides RP(O)(NCO)F 139

2.9. Alkylphosphonic Isothiocyanatofluorides RP(O)(NCS)F 140

2.10. Alkylphosphonic Diisocyanates RP(O)(NCO)2 141

2.11. Alkylphosphonic Diisothiocyanates RP(O)(NCS)2 143

2.12. Alkylphosphonic Acids RP(O)(OH)2 144

2.13. Dialkyl Alkylphosphonates RP(O)(OR)2 152

2.14. Dialkyl Arylphosphonates ArP(O)(OR)2 212

2.15. Dialkyl α-Ketophosphonates (RO)2P(O)C(O)R′ 226

2.16. Dialkyl α-Hydroxyphosphonates (RO)2P(O)CH(OH)R′ (Pudovik Reaction) 231

2.17. Dialkyl α-Siloxyphosphonates (RO)2P(O)CH(OSiMe3)R′ (Abramov Reaction) 237

2.18. Dialkyl α-Aminophosphonates (RO)2P(O)CR2NR2 (Kabachnik–Fields Reaction) 239

2.19. Dialkyl Alkenylphosphonates (RO)2P(O)C=CR2 248

2.20. Dialkyl Alkynylphosphonates (RO)2P(O)C2P(O)C≡CR 254

2.21. Alkyl Alkylphosphonochloridates R(R′O)P(O)Cl 258

2.22. N,N-Dialkyl Alkylphosphonamidochloridates R(R′2N)P(O)Cl 269

2.23. S-Alkyl Alkylphosphonochloridothiolates R(R′S)P(O)Cl 270

2.24. Alkyl Alkylphosphonofluoridates R(R′O)P(O)F 273

2.25. N-Alkyl or N,N-Dialkyl Alkylphosphonamidofluoridates R(R′XN)P(O)F (X = H or R′) 278

2.26. S-Alkyl Alkylphosphonofluoridothiolates R(R′S)P(O)F 280

2.27. Alkyl Alkylphosphonocyanidates R(R′O)P(O)CN 280

2.28. Alkyl Alkylphosphonic Acids R(R′O)P(O)OH 281

2.29. Alkylphosphonofluoridic Anhydrides R(F)P(O)OP(O)(F)R 292

2.30. Dialkyl Dialkylpyrophosphonates R(R′O)P(O)OP(O)(OR′)R 293

2.31. N,N-Dialkyl-P-Alkylphosphonamidic Anhydrides R(R′2N)P(O)OP(O)(NR′2)R 297

2.32. S,S′-Dialkyl Dialkyldithiopyrophosphonates R(R′S)P(O)OP(O)(SR′)R 298

2.33. O-Alkyl N-Alkyl Alkylphosphonamidates RP(O)(NR2)OR 299

2.34. Bis(N,N-Dialkyl) Alkylphosphonodiamidates RP(O)(NR2)2 302

2.35. O,S-Dialkyl Alkylphosphonothiolates RP(O)(OR)SR 306

2.36. S-Alkyl N-Alkyl (or N,N-Dialkyl) Alkylphosphonamidothiolates RP(O)(NR2)SR 310

2.37. S,S′-Dialkyl Alkylphosphonodithiolates RP(O)(SR2)2 311

References 313

3. Thiophosphonyl Compounds 327

3.1. Introduction 327

3.2. Alkylphosphonothioic Dichlorides RP(S)Cl2 328

3.3. Alkylphosphonothioic Difluorides RP(S)F2 335

3.4. Dialkyl Alkylphosphonothionates (RO)2P(S)R 336

3.5. Alkyl Alkylphosphonochloridothionates RO(R′)P(S)Cl 342

3.6. Alkyl Alkylphosphonofluoridothionates RO(R′)P(S)F 344

3.7. O-Alkyl Hydrogen Alkylphosphonothioates RO(R′)P(S)OH 346

3.8. Dialkyl Dialkylpyrophosphonodithionates RO(R′)P(S)OP(S)(R′)OR 353

3.9. S-Alkyl Alkylphosphonochloridothiolothionates RS(R′)P(S)Cl 354

3.10. N,N-Dialkyl P-alkylphosphonamidochloridothionates R2N(R′)P(S)Cl 354

3.11. N,N-Dialkyl P-alkylphosphonamidofluoridothionates R2N(R′)P(S)F 355

3.12. Alkyl Alkylphosphonocyanidothionates RO(R′)P(S)CN 356

3.13. Alkyl Alkyl/aryl Alkylphosphonothionates RO(R′)P(S)OR′′ 357

3.14. O-Alkyl N-alkyl/aryl Alkylphosphonamidothionates RO(R′)P(S)NR2 357

3.15. O-Alkyl S-alkyl Alkylphosphonodithioates RO(R′)P(S)SR 358

3.16. Bis(O-alkyl Alkylphosphinothioyl) Disulfides RO(R′)P(S)SSP(S)(R′)OR 360

3.17. Bis(N,N-dialkyl) Alkylphosphonodiamidothionates (R2N)2P(S)R′ 360

3.18. S,S′-Dialkyl Alkylphosphonodithiolothionates (RS)2P(S)R′ 361

References 363

4. Phosphoryl Compounds 365

4.1. Introduction 365

4.2. Alkyl Phosphorodichloridates ROP(O)Cl2 365

4.3. Aryl Phosphorodichloridates ArOP(O)Cl2 369

4.4. Alkyl Phosphorodifluoridates ROP(O)F2 371

4.5. Aryl Phosphorodifluoridates ArOP(O)F2 372

4.6. Alkyl N,N,N′,N′-tetraalkyl Phosphorodiamidates ROP(O)(NR2)2 373

4.7. Alkyl Phosphorodihydrazidates ROP(O)(NHNHR)2 374

4.8. Alkyl Phosphorodiisocyanatidates ROP(O)(NCO)2 375

4.9. Alkyl Phosphorodiisothiocyanatidates ROP(O)(NCS)2 376

4.10. Alkyl Dihydrogen Phosphates ROP(O)(OH)2 377

4.11. O,S,S′-Trialkyl Phosphorodithiolates ROP(O)(SR)2 379

4.12. O,S-Dialkyl Phosphorochloridothiolates RO(RS)P(O)Cl 379

4.13. O-Alkyl N,N-dialkylphosphoramidochloridates RO(R2N)P(O)Cl 381

4.14. S-Alkyl N,N-dialkylphosphoramidochloridothiolates RS(R2N)P(O)Cl 383

4.15. S,S′-Dialkyl Phosphorochloridodithiolates (RS)2P(O)Cl 384

4.16. O,S-Dialkyl Phosphorofluoridothiolates RO(RS)P(O)F 386

4.17. O-Alkyl N,N-dialkylphosphoramidofluoridates RO(R2N)P(O)F 386

4.18. Symmetrical Dialkyl H-phosphonates (RO)2P(O)H 387

4.19. Unsymmetrical Dialkyl H-phosphonates RO(R′O)P(O)H 398

4.20. Diaryl H-phosphonates (ArO)2P(O)H 400

4.21. Dialkyl Phosphorofluoridates (RO)2P(O)F 401

4.22. Dialkyl Phosphorochloridates (RO)2P(O)Cl 408

4.23. Diaryl Phosphorochloridates (ArO)2P(O)Cl 420

4.24. Dialkyl Phosphorobromidates (RO)2P(O)Br 421

4.25. Dialkyl Phosphoroiodidates (RO)2P(O)I 425

4.26. Dialkyl Phosphorocyanidates (RO)2P(O)CN 426

4.27. O-ALKYL Dialkoxyphosphinylformates (RO)2P(O)C(O)OR 431

4.28. S-Alkyl Dialkoxyphosphinylthioformates (RO)2P(O)C(O)SR 431

4.29. N-Alkyl Dialkoxyphosphinylformamides (RO)2P(O)C(O)NR2 432

4.30. [(Dialkoxyphosphinyl)formyl]-O-alkylhydroxamates (RO)2P(O)C(O)NHOR 433

4.31. S-Alkyl Dialkoxyphosphinyldithioformates (RO)2P(O)C(S)SR 434

4.32. Symmetrical Dialkyl Hydrogen Phosphates (RO)2P(O)OH 435

4.33. Unsymmetrical Dialkyl Hydrogen Phosphates RO(R′O)P(O)OH 437

4.34. Dialkyl Alkylperoxy Phosphates (RO)2P(O)OOR 438

4.35. Trialkyl Phosphates (RO)2P(O)OR 440

4.36. Diaryl Alkyl Phosphates (ArO)2P(O)OR 451

4.37. Triaryl Phosphates (ArO)3P=O 452

4.38. Dialkyl Alkylideneamino Phosphates (RO)2P(O)ON=CR2 (Allen Reaction) 455

4.39. Dialkyl Enolphosphates (RO)2P(O)OCR=CR2 (Perkow Reaction) 456

4.40. Dialkyl Phosphorazidates (RO)2P(O)N3 461

4.41. Dialkyl Phosphoramidates (RO)2P(O)NR2 (Todd–Atherton Reaction) 462

4.42. Dialkyl N-arylphosphoramidates (RO)2P(O)NHAr 478

4.43. Diaryl Phosphoramidates (ArO)2P(O)NR2 479

4.44. Dialkyl N-methyl-N-(phosphoryl)phosphoramidates (RO)2P(O)N(Me)P(X)R2 480

4.45. Dialkyl N-methyl-N-acylphosphoramidates (RO)2P(O)N(Me)COR′ 482

4.46. Disubstituted N-aryl(or alkyl)-N-chlorophosphoramidates (RO)2P(O)N(Cl)Ar 482

4.47. Dialkyl N,N-dihalophosphoramidates (RO)2P(O)NX2 (X = Cl or Br) 483

4.48. Dialkyl N-hydroxy/alkoxyphosphoramidates (RO)2P(O)NHOR (R = H or Alkyl) 485

4.49. Dialkyl Phosphorohydrazidates (RO)2P(O)NH2NH2 486

4.50. Dialkyl Phosphoroisocyanatidates (RO)2P(O)NCO 489

4.51. Dialkyl Phosphoroisothiocyanatidates (RO)2P(O)NCS 492

4.52. Dialkyl Phosphoro(thionylamidates) (RO)2P(O)NSO 494

4.53. N,N′-Bis(dialkylphosphoryl)sulfamides (RO)2P(O)NHSO2NHP(O)(OR)2 495

4.54. N-(Dialkylphosphoryl)aldimines (RO)2P(O)N=CHR 496

4.55. N-(Dialkylphosphoryl)guanidines (RO)2P(O)N=C(NR2)2 496

4.56. O,O-Dialkyl Hydrogen phosphorothioates (RO)2P(O)SH 498

4.57. O,O,S-Trialkyl Phosphorothiolates (RO)2P(O)SR 507

4.58. Dialkyl S-(S-alkyl) Phosphorothiolates (RO)2P(O)SSR 519

4.59. Dialkyl S-(O-alkyl) Phosphorothiolates (RO)2P(O)SOR 521

4.60. Dialkylphosphoryl Alkylsulfonates (RO)2P(O)S(O)OR 522

4.61. Tetraalkyl Pyrophosphates (RO)2P(O)OP(O)(OR)2 522

4.62. Bis(dialkylphosphoryl) Sulfides (RO)2P(O)SP(O)(OR)2 530

4.63. Bis(dialkylphosphoryl) Disulfides (RO)2P(O)SSP(O)(OR)2 534

4.64. Bis(dialkylphosphoryl) Sulfoxides (RO)2P(O)S(O)P(O)(OR)2 536

4.65. N-Alkylphosphoramidic Dichlorides RNHP(O)Cl2 537

4.66. N,N-Dialkylphosphoramidic Dichlorides R2NP(O)Cl2 538

4.67. N,N-Dialkylphosphoramidic Difluorides R2NP(O)F2 541

4.68. N,N,N′,N′-Tetraalkyl Phosphorodiamidites (R2N)2P(O)H 542

4.69. N,N,N′,N′-Tetraalkyl Phosphorodiamidochloridates (R2N)2P(O)Cl 544

4.70. Bis(N-alkyl) or N,N,N′,N′-tetraalkyl Phosphorodiamidofluoridates (R2N)2P(O)F 547

4.71. N,N,N′,N′-Tetraalkyl Phosphorodiamidoazidates (R2N)2P(O)N3 549

4.72. Bis(N,N-dialkyl) Pyrophosphorodiamidates (R2N)2P(O)OP(O)(NR2)2 550

4.73. Tri- and hexaalkylphosphoramides (RNH)3P=O and (R2N)3P=O 551

References 552

5. Thiophosphoryl Compounds 563

5.1. Introduction 563

5.2. Alkyl Phosphorodichloridothionates ROP(S)Cl2 564

5.3. Dialkyl H-thiophosphonates (RO)2P(S)H 566

5.4. Dialkyl Phosphorochloridothionates (RO)2P(S)Cl 569

5.5. Dialkyl Phosphorocyanidothionates (RO)2P(S)CN 574

5.6. O,O-Dialkyl Hydrogen Phosphorothioates (RO)2P(S)OH 575

5.7. Trialkyl (or Dialkyl Aryl) Phosphorothionates (RO)2P(S)OR′ 581

5.8. Dialkyl Enol Phosphorothionates (RO)2P(S)OCR=CR2′ 587

5.9. O,O-Dialkyl O-oximino Phosphorothionates (RO)2P(S)ON=CR2′ 588

5.10. O,O-Dialkyl O-acyl Phosphorothionates (RO)2P(S)OC(O)R′ 589

5.11. Dialkyl Phosphoramidothionates (RO)2P(S)NH2 591

5.12. S,S-Dialkyl Phosphoramidodithiolothionates (RS)2P(S)NHR′ 592

5.13. Tris(N,N-dialkylamino)Phosphorothionates (R2N)3P=S 593

5.14. Disubstituted N-(alkoxy)Phosphoramidothionates (RO)2P(S)NHOR′ 595

5.15. Dialkyl Phosphorohydrazidothionates (RO)2P(S)NR′NR2′ 595

5.16. Dialkyl PhosphoroisoCYANATIDOthionates (RO)2P(S)NCO 596

5.17. Dialkyl Phosphoroisothiocyanatidothionates (RO)2P(S)NCS 597

5.18. Dialkyl Phosphorazidothionates (RO)2P(S)N3 599

5.19. Dialkyl N-(phosphinimido)Phosphorothionates (RO)2P(S)N=PR3′ 601

5.20. O,O-Dialkyl S-(dialkylamino) Phosphorothiolothionates (RO)2P(S)SNR2′ 602

5.21. O,O-Dialkyl Hydrogen Phosphorodithioates (RO)2P(S)SH 603

5.22. O,O-Dialkyl S-alkyl Phosphorothiolothionates (RO)2P(S)SR′ 606

5.23. O,O-Dialkyl S-(alkyl/aryl-thio) Phosphorodithioates (RO)2P(S)SSR′ 612

5.24. O,O-Dialkyl S-(dialkylaminothio) Phosphorodithioates (RO)2p(S)SSNR2′ 614

5.25. O,O-Dialkyl S-(alkoxy) Phosphorodithioates (RO)2P(S)SOR′ 615

5.26. O,O-Dialkyl S-acyl Phosphorodithioates (RO)2P(S)SC(O)R′ 616

5.27. O,O-Dialkyl S-(N-alkylcarbamoyl) Phosphorodithioates (RO)2P(S)SC(O)NR2′ 620

5.28. Tetra-Alkyl Pyrophosphorodithionates (RO)2P(S)OP(S)(OR)2 622

5.29. Tetra-Alkyl Pyrophosphorothionates (RO)2P(S)OP(O)(OR)2 624

5.30. Tetra-Alkyl Thiopyrophosphorodithionates (RO)2P(S)S(S)P(OR)2 626

5.31. Bis(Dialkylthiophosphoryl) Disulfides (RO)2P(S)SSP(S)(OR)2 627

5.32. Tetra-Alkyl Carbonyl bis(phosphorodithioates) [(RO)2P(S)S]2C=O 627

References 628

6. Selenophosphorus Compounds 633

6.1. Introduction 633

6.2. Alkali Metal O,O-dialkyl Phosphoroselenoates (RO)2P(O)SeM 633

6.3. Dialkyl Phosphorochloridoselenonates (RO)2P(Se)Cl 641

6.4. Dialkyl Hydrogen Phosphoroselenoates (RO)2P(Se)OH and Phosphono and Phosphino Relatives: RO(R)P(Se)OH and R2P(Se)OH 643

6.5. Nucleoside H-phosphonoselenoate Monoesters (RO)P(O)(H)SeH and Diesters (RO)2P(Se)H 645

6.6. O,O,Se-Trisubstituted Phosphoroselenolates (RO)2P(O)SeR′ 647

6.7. Tetra-Alkyl Selenopyrophosphates (RO)2P(O)SeP(O)(OR)2 and bis(Dialkylphosphoryl) Diselenides (RO)2P(O)SeSeP(O)(OR)2 654

6.8. O,O-Dialkyl Phosphoroselenothioate Salts (RO)2P(S)SeM or (RO)2P(Se)SM and O,O,Se-trialkyl Phosphoroselenothionates (RO)2P(S)SeR or O,O,S-trialkyl Phosphoroselenothiolates (RO)2P(Se)SR 659

6.9. O,O,O-Trisubstituted Phosphoroselenonates (RO)3P=Se 663

6.10. O,O-Dialkyl Phosphorodiselenoate Salts (RO)2P(Se)SeM and O,O,Se-trialkyl Phosphorodiselenoates (RO)2P(Se)SeR′ 665

6.11. Halogenoselenophosphonium Salts [R3P+SeX]X− and [(RO)3P+SeX]X− 667

6.12. Secondary Phosphine Selenides R2P(Se)H 671

6.13. Tertiary Phosphine Selenides R3P=Se 673

6.14. Disubstituted Phosphinochloridoselenonates R2P(Se)Cl 677

6.15. Diselenophosphinoic Acid Salts R2P(Se)SeM 678

6.16. Esters of Diselenophosphinoic Acids R2P(Se)SeR′ 687

6.17. Bis(dialkylselenophosphinyl) Selenides [R2P(Se)]2Se and Diselenides [R2P(Se)]2Se2 691

6.18. Dialkyl Phosphinoselenothioate Salts R2P(S)SeM and Se-esters R2P(S)SeR′ 694

6.19. Woollin's REAGENT (WR) and Phosphorus–Selenium-Containing Derivatives 698

References 717

7. Analysis of Organophosphorus Chemicals 721

7.1. Introduction 721

7.2. Some Important Organophosphorus Chemicals 722

7.3. Analytical Techniques for the Analysis of Organophosphorus Chemicals 726

7.4. Concluding Comments 747

References 747

Index 753

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