Contents of Miniscale Procedures                               

                                                            *Applicable to Both Microscale and Miniscale

 

   Chapter One         Techniques in the Organic Chemistry Laboratory

 

*Exercise B.1:  Determining Density of an Aqueous

Solution     20

 

*Exercise B.2:  Determining Density of an Organic Liquid     21

 

                                                            *Exercise B.3:  Calibrating a Pasteur Pipet     21

 

                                                            *Exercise C.1:  Calibration of a Thermometer     26

 

                                                            *Exercise C.2:  Melting Point of an Unknown Solid     26

 

                                                            *Exercise C.3:  Mixed Melting Point     27 

 

Exercise D.2:  Determining the Boiling Point of an Unknown Liquid  30

 

*Exercise E.1:  Measuring the Refractive Index of an Unknown Liquid     33

 

Exercise F.2:  Recrystallizing an Impure Solid  48

 

Exercise F.3:  Recrystallizing Acetanilide with Hot Gravity Filtration  49

 

Exercise F.6:  Sublimation of Caffeine  51

 

Exercise G.2:  Distilling an Equimolar Mixture of Cyclohexane and Toluene  64

 

Exercise H.1:  Fractional Distillation of an Equimolar Cyclohexane/Toluene Mixture  70

 

Exercise H.2:  Steam Distillation of Lemon Grass Oil  71

 

Exercise 1.2:  Determining the Distribution Coefficient of Caffeine   80

 

*Exercise J.1:  Determining Relative Detector Response Factors in GC     89

 

*Exercise J.2:  Determining Mass Percent of a Mixture Using GC      90

 

*Exercise J.3:  Determining Mass Percent of a Mixture of Alcohols     90

 

*Exercise K.1:  Analysis of Analgesic Tablets by TLC  101

 

Exercise K.3:  Separating Ferrocene and Acetylferrocene Using Column Chromatography  102

 

*Exercise K.4:  HPLC Analysis of Benzaldehyde and Benzyl Alcohol  102

 

Exercise L.1:  Determining the Optical Purity of an Unknown Liquid  107

 

*Exercise L.2:  Determining the Melting Points of Enantiomers and Racemates    107

 

  Chapter Two           Spectroscopic Methods and Molecular Modeling

 

*Exercise M.1:  Determining the IR spectrum of an Organic Liquid    122

 

*Exercise M.2:  Determining the IR spectrum of an Organic Solid    122

 

                                    *Exercise M.3:  Spectroscopic Identification of Unknowns       122

 

                                    *Exercise N.1:  Recording a 1H NMR Spectrum     148

 

                                    *Exercise N.2:  Recording a 13C NMR Spectrum     148

 

*Exercise N.3:  1H NMR Spectral Problems     148

 

                                    *Exercise N.4:  13C NMR Spectral Problems     150

                                   

                                    *Exercise N.5:  Spectral Identification Using 1H and 13C NMR   151

 

                                    *Exercise P.1:  Solving Problems in Mass Spectrometry     172

 

                                    *Exercise Q.1:  Conformational Analysis of Butane and Other Molecules    180

 

                                    *Exercise Q.2:  Conformational Analysis of Propane            180

 

                                    *Exercise Q.3:  Conformational Analysis of 2-Methylbutane         181

 

                                    *Exercise Q.4:  Identifying Reactive Sites      181

                                   

                                    *Exercise Q.5:  Heats of Formation and Dipole Moments     181

 

                                    *Exercise Q.6:  LUMO Energies of Alkenes   181

 

                                    *Exercise Q.7:  Conformational Analysis of 3-Fluoropropene    182

 

Chapter Three          Applications Using Laboratory Resources and Techniques

 

                                    Experiment 3.1:  Scavenger Hunt:  Introduction to Chemical Data Reference Books and Calculations

 

                                    *Part A: Scavenger Hunt in the Chemical Reference Books  187

 

                                    *Part B:  Scavenger Hunt and Stoichiometric Calculations  188 

 

Experiment 3.2  Identification of Organic Liquids by Physical Properties

 

                                                                        Part A:  Boiling Point Determination  190

 

                                                            Experiment 3.3:  Relationships Between Structure and Physical Properties

 

                                                                        *Part A:  Determination of the Effect of Structure on Boiling Point  194 

 

                                                                        *Part B:  Determination of the Effect of Structure on Refractive Index   194

 

                                                                        *Part C:  Determination of the Effect of Structure on Melting Point               194

 

                                                            Experiment 3.5  Separations Based upon Acidity and Basicity

 

            *Part A:  Determination of Solubilities     202

 

            Part C:  Miniscale Separation of Benzoic Acid and Ethyl 4-Aminobenzoate    204

 

Experiment 3.6  Isolation of a Natural Product

 

            Part A:  Miniscale Extraction of Caffeine from Tea Leaves    207

 

            Part B:  Miniscale Extraction of Caffeine from Instant Coffee    208

 

            Part C:  Miniscale Isolation of Caffeine from NoDoz    209

 

            Part D:  Miniscale Isolation of Cholesterol from Simulated Gallstones  209

 

Experiment 3.6  Solvent and Polarity Effects in Thin-layer Chromatography

 

            *Part A:  Determining the Effect of Polarity on Elution     212

 

            *Part B:  Separation and Identification of Components of Components of a Mixture of trans-Stilbene,

                          9-Fluorenone and Benzoic Acid    214

 

Experiment 3.8:  Purification and analysis of a Liquid: Simple and Fractional Distillation       

 

            Part A: Miniscale Distillation    218

 

            Part B: Miniscale Fractional Distillation     219

 

  Chapter Five           Synthesis of Alkenes

 

Experiment 5.1  Alkenes via Acid-catalyzed Dehydration of Alcohols 

 

            Part B:  Miniscale Synthesis of Alkenes Via the Acid-catalyzed Dehydration of 3,3-Dimethyl-2-butanol     231

 

                          Chapter Six             Alkene Addition Reactions

 

                                                            Experiment 6.2 Hydration of Alkenes

 

                                                                        Part C:  Miniscale Hydration of Norbornene  245

 

                                                            Experiment 6.3  Preparation of Alcohols from Alkenes by

Hydroboration-oxidation

 

            Part B:  Miniscale Hydroboration-oxidation of 3.3-Dimethyl-1-butene  249

 

Experiment 6.4  Addition Polymers:  Preparation of Polystyrene and Polymethyl Methacrylate

 

            Part A:  Miniscale Polymerization of Styrene (Bulk method) 253

 

            Part C:  Miniscale Plymerization of Methyl Methacrylate (Bulk Method)  253

 

Chapter Seven         Stereochemistry

 

                                                            Experiment 7.1:  Stereochemistry of Alkenes and Derivatives

 

            Part C:  Determining the Mechanism of Isomerization of Dimethyl Maleate to Dimethyl Fumarate     259

 

            Chapter Eight            Introduction to Nucleophilic Substitution Reactions

 

Experiment 8.1:  Relative Rates of Nucleophilic Substitution Reactions    

 

            *Part A:  Determination of Factors Affecting the Relative Rates of SN2 Reactions    263

 

            *Part B:  Determination of Factors Affecting the Relative Rates of SN1 Reactions    264

 

                                                            Experiment 8.2  Nucleophilic Aliphatic Substitution:

Synthesis of 1-Bromobutane

 

            Part B:  Miniscale Synthesis of 1-Bromobutane  269

 

                        Chapter Nine             Dienes and Conjugation

 

                                                            Experiment 9.1  Dienes and the Diels-Alder Reaction

 

                                                                        Part B:  Miniscale Reaction of 1.3-Butadiene with Maleic Anhydride  277

 

                                                                        Part D:  Miniscale Reaction of Cyclopentadiene with Maleic Anhydride  277

 

            Part E:  Miniscale Reaction of Anthracene with Maleic Anhydride   278

 

                        Chapter Ten              Qualitative Organic Analysis I

 

*Experiment 10.1:  Qualitative Analysis of Alkyl Halides, Alkenes, Dienes, and Alkynes    281 

 

                        Chapter Twelve        Electrophilic Aromatic Substitution

 

                                                            Experiment 12.2  Nitration of Methyl Benzoate

 

                                                                        Part B:   Miniscale Nitration of Methyl Benzoate  306

 

Chapter Thirteen      Combined Spectroscopy and Advanced Spectroscopy

 

Experiment 13.1  Infrared and Nuclear Magnetic Resonance Spectroscopy of Alcohols, Ethers, and Phenols

 

            *Part A:  Experimental Procedure for Infrared Spectroscopy     326

 

            *Part B:  Experimental Procedure for IR and NMR Spectroscopy   326

 

            *Part C:  Exercises for IR and NMR Spectroscopy    327

 

Experiment 13.2  Combined Spectral Analysis:  Infrared, Ultraviolet, and Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry

 

            *Part A:  Purification of the Unknown    341

 

            *Part B:  Preparation of the Sample and Spectroscopic Analysis   341

 

            *Part C:  Spectroscopic Exercises      342

 

                      Chapter Fourteen       Organometallics

 

                                                            Experiment 14.1  Grignard Synthesis:  Preparation of Triphenylmethanol and 3-Methyl-2-phenyl-2-butanol

 

            Part B:  Miniscale Synthesis of Triphenylmethanol from Ethyl Benzoate  355

                                                           

Experiment 14.2  Using Indium Intermediates: Reaction of Allyl Bromide with an Aldehyde

 

Miniscale Reaction of 3-Bromopropene with o-Chlorobenzaldehyde and Indium    362 

(Refer to the Instructor’s guide for an updated procedure.)

 

                          Chapter Fifteen      Alcohols and Diols                                                     

 

*Experiment 15.2  Experimental Design for an Alcohol Oxidation    369

 

                        Chapter Sixteen       Ethers

 

                                                            Experiment 16.1  Ether Synthesis by SN2 Dispacement

 

                                                                        Part B:  Miniscale Preparation of Benzyl tert-Butyl Ether    379

 

Experiment 16.2  Nucleophilic Aliphatic Substitution Puzzle: Substitution Versus Elimination

 

Miniscale Reaction of Hydrobenzoin with Sodium Hydride and 1,3-Dibromopropane     382

 

                  Chapter Seventeen       Aldehydes and Ketones

 

                                                            Experiment 17.1  Stereoselective Synthesis of Alkenes

 

            Part B:  Miniscale Wittig Synthesis of trans-9-(2-Phenylethenyl)-anthracene  389

 

                                                            Experiment 17.2  Conversion of Cyclohexanone to Caprolactam

 

            Part B:  Miniscale Conversion of Cyclohexanone to Caprolactam  395

 

            B.1:  Preparation of Cyclohexanone Oxime  395

            B.2:  Beckmann Rearrangement of Cyclohexanone to Caprolactam  396

 

Experiment 17.3  Pinacol Rearrangement and

Photochemical Synthesis of Benzopinacol

 

                                                                        Part B:  Miniscale Photoreduction of Benzophenone  401

 

                                                                        Part C:  Miniscale Synthesis of Benzopinacolone  402

 

                        Chapter Eighteen     Enols, Enolates and Enones

                                                           

Experiment 18.1  Preparation of a,b-Unsaturated Ketones via Mixed Aldol Condensation

 

                                                                        Part A:  Miniscale Synthesis of 1.9-Diphenyl-1.3.6.8-Nonatetraen-5-one (Dicinnamalacetone)  407

 

            Part C:  Identification of a Mixed Aldol Product for the Condensation of an Unknown Aromatic Aldehyde with

                         a Ketone  410

 

Experiment 18.3  Identification of Products of Catalytic Transfer Hydrogenation of an Enone

 

            Part B:  Microscale Reaction of 2-Cyclohexenone       416

 

                        Chapter Nineteen     Carboxylic Acids

 

                                                            Experiment 19.1  Synthesis and Identification of an Unknown Carboxylic Acid

 

                                                            Miniscale Grignard Synthesis of Substituted Benzoic Acids     422

 

                        Chapter Twenty        Carboxylic Acid Esters

 

Experiment 20.2  Synthesis of Esters by Baeyer-Villiger Oxidation

 

            Part B:  Microscale Oxidation of Cyclohexanone       437

 

              Chapter Twenty-One         Dicarbonyl Compounds

 

Experiment 21.1  Base-Catalyzed Condensations of Dicarbonyl Compounds

 

            Part B:  Miniscale Preparation of Coumarin or a Coumarin Derivative               444

                                               

Chapter Twenty-Two           Amines

 

                                                Experiment 22.1  Relating Color to Structure: Synthesis of Azo Dyes

 

                                                            Part A:  Miniscale Diazotization of an Aromatic Amine     454

 

                                                            Part B.1:  Miniscale Coupling with a Phenol     455

 

                                                            Part B.2:  Miniscale Coupling with an Amine    455

 

                                                            Part C:  Direct dyeing with the Azo Dye     455

 

                                                            Part D:  Recording the UV-Visible Spectrum of the Prepared Dyes   455

 

                                                            Part E:  Determining the pH Indicator range of the Prepared Dyes    455

 

                                                            Part F:  Determining Antibacterial Properties of Dye (Optional)

 

                                                Experiment 22.2  Synthesis of Pyrrole and Pyrimidine Derivatives

 

                                                            Part B:  Miniscale Synthesis of a Five-Member Ring Heterocycle from Hydrazine and an Unknown

                                                                         Diketone      461

 

                                                            Part D:  Miniscale Synthesis of a Substituted Pyrimidine   462

 

                                                Experiment 22.3  Synthesis of Heterocyclic Compounds

 

                                                            Part A:  Miniscale Reaction of Pyrrole and an Unknown Aromatic Aldehyde       466       

 

Experiment 22.4  Synthesis of Heterocycles and Kinetics by Spectroscopic Analysis

 

            Part A:  Miniscale Preparation of Lophines (2-Aryl-4,5- diphenylimidazoles      471

 

            Part B:  Miniscale Synthesis of Substituted Lophinyl (2-Aryl-4,5-diphenylimidazole) Dimers       471

 

            Part C:  Kinetics of Recombination Reaction        472

 

Chapter Twenty Four           Phenols

 

                                                            Experiment 24.1  Exploring Structure-Function Relationships of Phenols: Synthesis of Salicylic Acid, Aspirin and

                                                            Vanillin Derivatives

 

                                                                        Part A:  Miniscale Reactions of Vanillin      483

 

                                                                        Part B:  Miniscale Hydrolysis of Methyl Salicylate      485

 

                                                                        Part C:  Miniscale Synthesis of Acetylsalicylic Acid        486   

 

            Chapter Twenty Five           Carbohydrates

 

*Experiment 25.1  Classiification of Sugars and Identification of an Unknown Sugar   

 

*General Instructions for the Microscale Identification of an Unknown Sugar      495

 

                                                            Experiment 25.2  Esterification of Sugars:  Preparation of Sucrose Octaacetate and a- and

                                                            b-D-Glucopyranose Pentaacetate   

 

            Part D:  Miniscale Preparation of a-D-Glucose Pentaacetate and Measurement of Optical Rotation     503

 

            Chapter Twenty Six             Lipids

 

                                                            Experiment 26.1  Soap from a Spice: Isolation, Identification and Hydrolysis of a Triglyceride

 

            Part A:   Miniscale Isolation of a Triglyceride from Nutmeg     509

 

Experiment 26.2  Preparation of Esters of Cholesterol and Determination of Liquid Crystal Behavior

 

Miniscale Synthesis of Esters of Cholesterol       515                       

 

         Chapter Twenty Seven           Amino Acids and Derivatives

 

                                                            Experiment 27.1  Conversion of an Amino Acid to a Sunscreen: Multistep Preparation of Benzocaine or a

                                                            Benzocaine Analog

 

                                                                        Part A:  Miniscale Synthesis of p-Acetanilide     521

 

                                                                        Part B:  Miniscale Synthesis of p-Acetamidobenzoic Acid       522

 

                                                                        Part C:  Miniscale synthesis of p-Aminobenzoic Acid       523

 

                                                                        *Part E:  Determining the Effectiveness of the p-Aminobenzoic Acid Ester as a Sunscreen     526

 

            Chapter Twenty Eight          Qualitative Organic Analysis II

 

Experiment 28.2  Experimental Methods of Qualitative Analysis

 

            *Part A:  Purification of Unknown  559

 

            *Part B:  Solubility  Tests  559

 

            *Part C:  Chemical Tests  560

 

            *Part D:  Derivatives  566

 

            Chapter Twenty Nine           Projects

 

                                                            Experiment 29.1:  Multistep Synthesis of 1-Bromo-3-chloro-5-iodobenzene from Aniline

 

                                                                        Part A:  Synthesis of Acetanilide from Aniline      583

 

                                                                        Part B:  Miniscale Synthesis of 4-Bromoacetanilide from Acetanilide     585

 

                                                                        Part C:  Synthesis of 4-Bromo-2-chloroacetanilide from 4-Bromoacetanilide      586

 

                                                                        Part D:  Synthesis of 4-Bromo-2-chloroaniline from 4-Bromo-2-chloroacetanilide        587

 

                                                                        Part E:  Miniscale Synthesis of 4-Bromo-2-chloro-6-ioodaniline from 4-Bromo-2-chloroaniline      589

 

                                                                        Part F:  Synthesis of 1-Bromo-3-chloro-5-iodobenzene from 4-Bromo-2-chloro-6-iodoaniline      590

 

                                                            Experiment 29.2:  Multistep Synthesis of Sulfanilamide Derivatives as Growth Inhibitors

 

                                                                        Part A:  Miniscale Synthesis of Acetanilide     597

 

                                                                        Part B:  Miniscale Synthesis of p-Acetamidobenzenesulfonyl Chloride                597

 

                                                                        Part C:  Miniscale Synthesis of Sulfonamides      598

 

                                                                        Part D:  Miniscale Synthesis of Sulfanilamides      599

 

                                                                        Part E:  Bacterial Testing of Antibiotic Susceptibility       600

 

                                                            Experiment 29.3  Structural Determination of Isomers Using Decoupling and Special NMR Techniques

 

                                                                        *Part A:  Homonuclear Decoupling of a Known Alkene and Determination of Coupling Constants      612

 

                                                                        *Part B:  Characterization of an Unknown Compound Using Homonuclear Decoupling in

                                                                                      1H NMR Spectroscopy       612

 

                                                                        *Part C:  Characterization of an Unknown Compound Using 1H NMR Spectroscopy,

                                                                                      13C NMR spectroscopy, 1H-1H-COSY and HETCOR (1H-13C-COSY)       613

 

                                                            Experiment 29.4  The Library-Laboratory Connection

 

                                                                        *Part A:  Chemical Abstracts (CA) and Beilstein  614

 

                                                                        *Part B:  Searching Science Library Databases  619

 

                                                                        *Part C:  Searching on the Web      620

 

Experiment 29.5:  Stereochemistry, Molecular Modeling, and Conformational Analysis    

 

            *Part A:  Molecular Models Using a Molecular Model Kit     624

 

            *Part B:  Computer Modeling     625

 

            *Part C:  Conformational Analysis of Rotational Isomers   625

 

            *Part D:  Using Molecular Modeling to Analyze Rotational Conformations of Stereoisomers      625