Preparation of compounds labeled with tritium and carbon-14

670 Pages·2009·18.56 MB·English

by  Rolf Voges

Preparation of Compounds Labeled
with Tritium and Carbon-14
Preparation of Compounds Labeled with Tritium and Carbon-14 Rolf Voges, J. Richard Heys and Thomas Moenius
© 2009 John Wiley & Sons, Ltd. ISBN: 978-0-470-51607-2
Preparation of Compounds Labeled
with Tritium and Carbon-14
ROLF VOGES
J. RICHARD HEYS
THOMAS MOENIUS
Thiseditionfirstpublished2009
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LibraryofCongressCataloging-in-PublicationData
Voges,R.(Rolf)
Preparationofcompoundslabeledwithtritiumandcarbon-14/RolfVoges,
J.RichardHeys,ThomasMoenius.
p.cm.
Includesbibliographicalreferencesandindex.
ISBN978-0-470-51607-2
1. Organiccompounds–Synthesis.2. Radiolabeling.3. Tritium.4. Carbon–Isotopes.
I.Heys,J.R.(J.Richard)II.Moenius,Thomas.III.Title.
QD262.V542009
572’.36–dc22 2008046982
AcataloguerecordforthisbookisavailablefromtheBritishLibrary.
ISBN9780470516072(Hbk)
Typesetin10/12ptTimesbyThomsonDigital,Noida,India.
PrintedandboundinGreatBritainbyCPIAntonyRowe,Chippenham,Wiltshire
Contents
Preface xi
Glossary xiii
Author Biographies xvii
1 Introduction 1
1.1 Physical Properties of Tritium and Carbon-14 3
1.2 Purification 5
1.3 Analysis 6
1.3.1 Chemical Identity 6
1.3.2 Chemical (and Enantiomeric) Purity 7
1.3.3 Radiochemical (and Radionuclidic) Purity 8
1.3.4 Specific Activity 9
1.3.5 Position of Label 10
1.4 Stability and Storage of Compounds Labeled with Tritium
or Carbon-14 11
1.5 Specialist Techniques and Equipment 15
References 21
2 Strategies for Target Preparation 25
2.1 Formulating Target Specifications 26
2.2 Planning Radiotracer Preparations 31
2.2.1 The Construction Strategy 31
2.2.2 Reconstitution Strategies 32
2.2.3 The Derivatization Strategy 34
2.2.4 Selection of an Appropriate Strategy 34
2.2.5 Case Studies of Strategy Development 36
References 44
3 Preparation of Tritium-Labeled Compounds by Isotope Exchange
Reactions 47
3.1 Homogeneous Acid- or Base-Catalyzed Exchange 49
3.1.1 Exchange without Added Acid or Base 49
vi Contents
3.1.2 Exchange under Acidic Conditions 51
3.1.3 Exchange under Basic Conditions 56
3.2 Heterogeneous Catalysis with Tritium in Solvent 60
3.2.1 Metals 61
3.2.2 Other Catalysts 65
3.3 Heterogeneous Catalysis in Solution with Tritium Gas 66
3.3.1 Metal Catalysts with Nonreducible Substrates
in Aqueous Solution 67
3.3.2 MetalCatalystswithNonreducibleSubstratesinOrganicSolvents 68
3.3.3 Other Catalysts 69
3.3.4 Metal Catalysts with Reducible Substrates 70
3.4 Homogeneous Catalysis in Solution with Tritiated Water 71
3.4.1 Exchange Catalyzed by Metal Salts 71
3.4.2 Exchange Catalyzed by Organoruthenium Complexes 73
3.4.3 Exchange Catalyzed by Iridium Dionates 74
3.4.4 Exchange Catalyzed by Iridium Cyclopentadienides 76
3.5 Homogeneous Catalysis with Tritium Gas 77
3.5.1 Iridium Phosphines 77
3.5.2 Iridium Dionate Complexes 90
3.5.3 Iridium Cyclopentadienide Complexes 91
3.6 Solvent-Free Catalytic Exchange 93
3.6.1 High-Temperature Solid-State Catalytic Isotope Exchange 93
3.6.2 Thermal Tritium Atom Bombardment 96
3.6.3 Other Radiation-Induced Labeling Methods 97
References 98
4 Preparation of Tritium-Labeled Compounds by Chemical Synthesis 109
4.1 Catalytic Tritiations 110
4.1.1 Tritiation of Carbon–Carbon Multiple Bonds 111
4.1.2 Tritiation of Carbon–Heteroatom Multiple Bonds 125
4.1.3 Homogeneously Catalyzed Reactions 126
4.2 Catalytic Tritiolyses 132
4.2.1 Tritiodehalogenations 133
4.2.2 Tritiolyses of Benzylic N- and O-Functions 144
4.2.3 Tritiodesulfurizations 145
4.3 Tritide Reductions 146
4.3.1 Sodium Borotritide (NaB3H ) 148
4
4.3.2 Sodium Cyanoborotritide (NaB3H CN) 157
3
4.3.3 Sodium/Tetramethylammonium Triacetoxyborotritide
[Na/NMe B3H(OAc) ] 159
4 3
4.3.4 Lithium Tritide (Li3H) 160
4.3.5 Lithium Borotritide (LiB3H ) 161
4
4.3.6 Lithium Triethylborotritide (LiEt B3H, Li-Super-Tritide) 163
3
4.3.7 Lithium Tri-sec-Butylborotritide [Li(sec-Bu )B3H,
3
Li T-Selectride] 165
4.3.8 Lithium [3H ]Boratabicyclo[3.3.1]nonane 166
2
Contents vii
4.3.9 Tritiated Borane (THF-Complex) (B 3H ; B3H .THF) 167
2 6 3
4.3.10 Tritiated Alkylboranes 169
4.3.11 Lithium Aluminum Tritide (LiAl3H ) 170
4
4.3.12 Tri-n-Butyltin Tritide (n-Bu Sn3H) 172
3
4.3.13 Tritiated Schwartz’s Reagent (ZrCp Cl3H) 176
2
4.3.14 Tritiated Triethylsilane and Trihexylsilane 177
4.4 Small Tritiated Building Blocks 178
4.4.1 Tritiated Water (3H O; 3HHO) 179
2
4.4.2 Tritiated Diimide (3HN ¼ N3H) 182
4.4.3 Tritiated Methyl Iodide (C3H I; C3HH I) 183
3 2
4.4.4 Tritiated Diiodomethane (C3HHI ) 190
2
4.4.5 Tritiated Formaldehyde (3HCHO, 3HC3HO) 191
4.4.6 Dimethyl[3H]formamide (3HCONMe ), Acetic
2
[3H]Formic Anhydride (3HCOOCOMe) 192
4.4.7 Tritiated Diazomethane (C3HHN ) 193
2
4.4.8 N-Tritioacetoxyphthalimide 194
4.4.9 N-Succinimidyl [2,3-3H]Propionate ([3H]NSP) 195
References 195
5 Barium [14C]Carbonate and the Preparation of Carbon-14-Labeled
Compounds via One-Carbon Building Blocks of the [14C]Carbon
Dioxide Tree 211
5.1 [14C]Carbon Dioxide (14CO ) 212
2
5.1.1 [14C]Carboxylations of Organometallic Compounds 212
5.1.2 Manipulations of [14C]Carboxylation Products 218
5.1.3 N-[14C]Acyl Building Blocks 219
5.1.4 PreparationofOtherBuildingBlocksfrom[14C]CarbonDioxide 221
5.2 [14C]Carbon Monoxide (14CO) 222
5.2.1 [14C]Phosgene 229
5.3 [14C]Formic Acid (H14COOH) 233
5.4 [14C]Formaldehyde (H14CHO) 240
5.4.1 Carbanion-Mediated Hydroxy[14C]methylation
and [14C]Methylenenation 242
5.4.2 Acid-Catalyzed Hydroxy[14C]methylations 246
5.4.3 Amino[14C]methylations 248
5.4.4 Reductive Methylations 254
5.4.5 Polycondensations 255
5.4.6 Thio[14C]methylations 256
5.5 [14C]Methyl Iodide (14CH I) 256
3
5.5.1 [14C]Methyl Iodide as an Electrophilic One-[14C]Carbon
Building Block 257
5.5.2 [14C]Methyl Iodide as a Source of Nucleophilic [14C]Methyl
and [14C]Methylene Building Blocks 262
5.5.3 Further Building Blocks Derived from [14C]Methyl Iodide 268
5.6 [14C]Nitromethane (14CH NO ) 270
3 2
References 277
viii Contents
6 Preparation of Carbon-14-Labeled Compounds via Multi-Carbon
Building Blocks of the [14C]Carbon Dioxide Tree 287
6.1 [14C]Acetic Acid and Its Derivatives 287
6.1.1 [14C]Acetic Acid 287
6.1.2 [14C]Acetyl Chloride 289
6.1.3 [14C]Acetic Anhydride 298
6.1.4 [14C]Acetic Acid Alkyl/Aryl Esters 301
6.2 Halo[14C]acetates 307
6.2.1 Reaction at the Carboxyl Group 309
6.2.2 Reactions at the Methylene Group 312
6.2.3 Reactions at the Halogen Atom 314
6.3 [14C]Acetone 337
6.3.1 Reaction at the Carbonyl Group 338
6.3.2 Reaction at the Methyl Group 343
6.4 Alkyl [14C]Acetoacetate 346
6.4.1 Alkylation Reactions 348
6.4.2 Acylation Reactions 351
6.4.3 Aldol Reactions 352
6.4.4 Knoevenagel–Michael Reactions 353
6.4.5 Reactions at the Functional Groups 356
6.5 [14C]Malonates 357
6.5.1 Reactions at the Methylene Group 359
6.5.2 Reactions at the Carboxyl Functions 374
References 381
7 Preparation of Carbon-14-Labeled Compounds
via the [14C]Cyanide Tree 393
7.1 Metal [14C]Cyanides 393
7.1.1 Preparation 393
7.1.2 Introduction of [14C]Cyanide into Organic Substrates 394
7.1.3 Synthetic Transformations of Organic [14C]Nitriles 399
7.2 Preparation of Other Building Blocks from [14C]Cyanide 411
7.2.1 Trimethylsilyl[14C]cyanide (TMS14CN) 412
7.2.2 [14C]Cyanogen Bromide (Br14CN) 413
7.2.3 Alkali Metal [14C]Cyanates (M14CNO; M ¼ Na, K) 415
7.2.4 Alkali Metal Thio[14C]cyanate (M14CNS; M ¼ Na, K) 417
7.2.5 Triethyl [14C]Orthoformate [H14C(OEt) ] 419
3
7.2.6 [14C]Cyanoacetic Acid [14CNCH COOH] 420
2
7.2.7 [14C]Diazomethane (14CH N ) 431
2 2
References 433
8 Preparation of Carbon-14-Labeled Compounds
via the [14C ]Acetylene Tree 441
2
8.1 [14C ]Acetylene (H14C:14CH) 441
2
8.2 [14C ]Acetaldehyde (14CH 14CHO) 445
2 3
8.3 [1,2-14C ]Acetic Acid (14CH 14COOH) 446
2 3
Contents ix
8.4 2-[2,3-14C ]Propyne-1-ol ([2,3-14C ]Propargyl Alcohol)
2 2
and 2-[2,3-14C ]Butyne-1,4-diol 447
2
8.5 Methyl [2,3-14C ]Propiolate (H14C(cid:2)14CCOOMe) and Dimethyl
2
[2,3-14C ]Acetylenedicarboxylate (HOOC14C(cid:2)14CCOOH) 447
2
8.6 1,2-[14C ]Dibromoethane (Br14CH 14CH Br) 448
2 2 2
8.7 [14C ]Ethylene Oxide 448
2
8.8 [14Cn]Benzene and the Synthesis of Ring-Labeled Aromatic
Compounds 448
8.8.1 Nitrobenzene Branch 451
8.8.2 Phenol Branch 454
8.8.3 Bromobenzene Branch 456
8.8.4 Iodobenzene Branch 457
8.8.5 Benzoic Acid Branch 458
8.8.6 Alkyl Phenyl Ketone Branch 459
8.8.7 Sulfonylbenzene Branch 459
References 460
9 Preparation of Carbon-14-Labeled Compounds
via the [14C]Cyanamide Tree 465
9.1 [14C]Cyanamide (H N14C(cid:2)N) 465
2
9.2 [14C]Guanidine (H N14C(¼NH)NH ) 467
2 2
9.3 [14C]Urea, H N14CONH 468
2 2
9.4 [14C]Thiourea, H N14CSNH 472
2 2
References 477
10 Reconstitution Strategies 479
10.1 Replacement Strategies 479
10.1.1 1H/3H Replacement Strategies 479
10.1.2 12C/14C Replacement Strategies 485
10.2 Disconnection–Reconnection Strategies 488
10.2.1 Dealkylation–Re[3H/14C]alkylation Procedures 488
10.2.2 CO /14CO Replacement Strategies 492
2 2
10.2.3 CO/14CO Replacement Strategy 501
10.2.4 Oxidative Cleavage of C¼C Bonds in the Reconstitution
Approach 502
References 517
11 Preparation of Enantiomerically Pure Compounds Labeled
with Isotopes of Hydrogen and Carbon 523
11.1 Resolution of Racemates 524
11.2 Enantioselective Synthetic Methods 529
11.2.1 Hydrogenation/Tritiation of Labeled/Unlabeled (cid:2)2,3-Amino
Acid Derivatives 530
11.2.2 Reduction of Labeled Prochiral Carbonyl Compounds
and Oximes 535
11.2.3 Enantioselective Oxidation of Olefins and Allylic Alcohols 541
x Contents
11.3 Diastereoselective Synthetic Procedures 546
11.3.1 (cid:1)-Alkylation of Chiral Imide Enolates 551
11.3.2 Aldol Reactions of Chiral Imides and Ester Enolates 558
11.3.3 1,4-Additions of Chiral Imide Enolates to Michael Acceptors 564
11.3.4 (cid:1)-Amination of Chiral Imide Enolates 566
11.3.5 (cid:1)-Hydroxylation of Chiral Imide Enolates 571
11.3.6 (cid:1)-Alkylation of Chiral Glycinates 571
11.3.7 Aldol Reactions of Chiral Glycinates 583
11.3.8 Aldol Reactions of Chiral Glycolates 586
11.3.9 Aldol Reactions of Chiral Haloacetates 586
11.3.10 Reactions on Chiral (cid:1),(cid:3)-Unsaturated Imides and Esters 591
References 596
12 Biotransformations in the Preparation of Compounds Labeled
with Carbon and Hydrogen Isotopes 607
12.1 Applications of Isolated Enzymes 608
12.1.1 Optical Resolutions via Derivatives 608
12.1.2 Synthesis of Isotopically Labeled, Enantiomerically
Pure Compounds 612
12.1.3 Conjugation Reactions 618
12.2 Application of Cell-Containing Systems 618
12.2.1 Transformations of Functional Groups 619
12.2.2 Fermentative Synthesis of Structurally Complex Molecules
by Incorporation of Labeled Precursors 621
12.2.3 Specific Requirements for Fermentations Using Isotopically
Labeled Compounds 623
12.3 Biocatalyzed Synthesis of Key Intermediates for Reconstitution
Approaches 630
12.3.1 Oxidation–Reduction Approach 631
12.3.2 Dealkylation–Realkylation Approach 632
References 634
Index 639