Experimental Organic

Size: px

Start display at page:

Download "Experimental Organic"

Charla Collins
5 years ago
Views:

1 Experimental Organic A Small-Scale Approach Second Edition Charles F. Wilcox, Jr. Cornell University Mary F. Wilcox Ithaca College PRENTICE-HALL, Englewood Cliffs, New Jersey 07632

"»Ij ntents INTRODUCTION Safety in the Laboratory 1.1 Laboratory Accidents 3 1.2 Fire and Explosion Hazards 4 1.3 Glassware Cuts 4 1.4 Corrosive Chemicals 5 1.5 Toxic Chemicals and Mutagens 6 1.

2 "»Ij ntents INTRODUCTION Safety in the Laboratory 1.1 Laboratory Accidents Fire and Explosion Hazards Glassware Cuts Corrosive Chemicals Toxic Chemicals and Mutagens The OSHA Laboratory Standard 6 General Remarks 2.1 Preparation Before the Laboratory Laboratory Directions In the Laboratory Calculation of Yields Samples and Reports Disposal of Chemical Wastes 17 Basic Laboratory Operations 3.1 Apparatus Cleaning and Drying Glassware Apparatus with Interchangeable Ground-Glass Joints Weighing and Measuring Reagents Heat Sources 24

3.6 Exercises on Basic Laboratory Operations 26 (A) Heating Rate 26 (B) Calibration of Pasteur Pipet Drop Size 26 (C) Identification of an Unknown from Its Density 27 4 Accessory Operations 4.

3 3.6 Exercises on Basic Laboratory Operations 26 (A) Heating Rate 26 (B) Calibration of Pasteur Pipet Drop Size 26 (C) Identification of an Unknown from Its Density 27 4 Accessory Operations 4.1 Drying Agents Cooling Baths Vacuum Pumps Refluxing Sample Addition Gas Absorption Traps Stirring Rotatory Evaporation 39 SEPARATION AND PURIFICATION OF ORGANIC COMPOUNDS 5 Simple and Fractional Distillation 5.1 Principles of Distillation Fractional Distillation Laboratory Practice Representative Simple and Fractional Distillations 66 (A) Distillation of a Pure Compound 66 (B) Distillation of a Mixture 66 (C) Methanol and Water 67 (D) Acetic Acid and Water 67 Questions 68 6 Vacuum Distillation 6.1 Effect of Pressure on Boiling Point Vacuum Pumps Laboratory Practice Representative Vacuum Distillations 75 (A) Purification of Methyl Benzoate 75 (B) Purification of Benzaldehyde 75 Questions 76 7 Steam Distillation 7.1 Principles of Steam Distillation Distillation Temperature and Composition of Distillate 7.3 Laboratory Practice 80

4 CONTENTS VÜ 7.4 Representative Steam Distillations 81 (A) Steam Distillation of Turpentine 81 (B) Separation of a Mixture by Steam Distillation 82 Questions 83 8 Melting Points, Crystallization, and Sublimation Melting Points Crystallization Sublimation Representative Procedures 98 (A) Melting Point of Mixtures 98 (B) Crystallization of Benzoic Acid from Water 98 (C) Crystallization of Acetanilide from Water 100 (D) Crystallization from a Flammable Solvent 100 (E) Small-Scale Recrystallization 101 (F) Selection of a Recrystallization Solvent 101 (G) Sublimation 102 Questions Extraction with Solvents 9.1 Extraction of Solids Extraction of Solutions Multiple Extractions Solubility Relationships Laboratory Practice Separation of Mixtures Containing Multiple Components 9.7 Representative Extractions 115 (A) Simple and Multiple Extraction 115 (B) Separation of Benzoic Acid and Acetanilide 117 (C) Separation of Benzoic Acid and Dimethyl Terephthalate 117 (D) Extraction of Caffeine from Tea 118 (E) Extraction of Trimyristin from Nutmeg 120 Questions Chromatography Introduction Liquid-Solid Chromatography Ion-Exchange Chromatography Liquid-Liquid Chromatography Gas-Liquid Chromatography Laboratory Practice Chromatographie Separations 142 (A) Separation of Ink Pigments by Thin-Layer Chromatography 143

viii CONTENTS (B) Separation of Plant Pigments by Thin-Layer Chromatography 143 (C) Analysis of Analgesics by Thin-Layer Chromatography 144 (D) Separation of a Dye Mixture 145 (E) Flash

5 viii CONTENTS (B) Separation of Plant Pigments by Thin-Layer Chromatography 143 (C) Analysis of Analgesics by Thin-Layer Chromatography 144 (D) Separation of a Dye Mixture 145 (E) Flash Chromatography 145 (F) Gas-Liquid Chromatography 146 Questions 146 JI J IDENTIFICATION OF ORGANIC COMPOUNDS 11 Identification by Chemical Methods Introduction Preliminary Examination Purification of the Unknown Sample Physical Constants Element Detection Solubility Classification Functional Group Identification 164 (A) Alcohols 166 (B) Aldehydes and Ketones 168 (C) Esters 171 (D) Carboxylic Acids 172 (E) Sulfonic Acids 172 (F) Carboxamides and Nitriles 172 (G) Amines 173 (H) Phenols 175 (I) Nonaromatic Hydrocarbons 176 (J) Aromatic Hydrocarbons 177 (K) Alkyl and Aryl Halides Derivatization of Functional Groups 179 (A) Alcohols 180 (B) Aldehydes and Ketones 184 (C) Esters 189 (D) Carboxylic Acids 192 (E) Sulfonic Acids 194 (F) Nitriles and Amides 197 (G) Amines 199 (H) Phenols 202 (I) Hydrocarbons and Halohydrocarbons 206 Questions Mass Spectrometry 12.1 Introduction Generation of Ions

CONTENTS ix 12.3 Mass Analysis 213 12.4 Elemental Composition 215 12.5 Basic Mechanisms of Ion Fragmentation 230 12.6 Spectral Features of Common Classes of Compounds 224 12.

6 CONTENTS ix 12.3 Mass Analysis Elemental Composition Basic Mechanisms of Ion Fragmentation Spectral Features of Common Classes of Compounds Sample Problem Solution 229 Questions Infrared Spectroscopy Introduction Structure and Infrared Absorption Frequencies Assignment of Principal Functional Groups Spectroscopic Details for Selected Functional Groups Infrared Sampling Techniques 250 Questions Visible and Ultraviolet Spectroscopy Introduction Ultraviolet and Visible Spectroscopy Ultraviolet and Visible Spectral Sampling Techniques 261 Questions Nuclear Magnetic Resonance Introduction >H Chemical Shifts Hydroxyl Protons and Proton Exchange C Chemical Shifts Signal Intensities Spin-Spin Interactions Representative Applications of 'H NMR in Structure Elucidation NMR Sampling Techniques 287 Questions 288 PREPARATION AND REACTIONS OF TYPICAL ORGANIC COMPOUNDS 16 Isolation and Identification of Orange-Peel Oil Isolation of Orange-Peel Oil Identification of Orange-Peel Oil 295 (A) Chemical Analysis 295 (B) Determination of Boiling Point 298 (C) Spectroscopic Identification 298 Questions 298

X CONTENTS 17 Free-Radical Halogenation 299 17.1 Mechanism of Free-Radical Chlorination 299 17.2 Chlorination by Means of Sulfuryl Chloride and AIBN 300 17.3 Energetics of Halogenation 301 17.

7 X CONTENTS 17 Free-Radical Halogenation Mechanism of Free-Radical Chlorination Chlorination by Means of Sulfuryl Chloride and AIBN Energetics of Halogenation Selectivity of Halogenations Substituent Effects Preparations and Reactions 305 (A) Photochemical Chlorination of Adamantane 305 (B) Photochemical Chlorination of 2,3-Dimethylbutane 306 (C) Substituent Effects in Free-Radical Chlorination 307 Questions Conversion of Alcohols to Alkyl Halides Preparation of Alkyl Halides Reactions of Alkyl Halides Preparations 312 (A) Butyl Bromide 312 (B) Cyclohexyl Chloride 314 (C) tert-butyl Chloride 315 Questions Second-Order Nucleophilic Substitution Replacement Reactions Stereochemistry and Kinetics Nucleophilicity Substrate Structure Solvent Preparation of Butyl Iodide 320 Questions Chemical Kinetics: Solvolysis of tert-butyl Chloride First-Order Kinetics Effect of Solvent on Rate of Solvolysis Laboratory Practice Measurement of the S N 1 Reaction Rate of tert-butyl Chloride 325 Questions Alkenes: El and E2 Reactions Sources of Alkenes Carbocation Rearrangements Dimerization of Isobutylene (2-Methylpropene) Reactions of Alkenes 330

8 CONTENTS xi 21.5 Preparations 331 (A) Cyclohexene 331 (B) Oxidation of Cyclohexene to Adipic Acid 331 (C) 2,4,4-Trimefhyl-l- and -2-pentenes (Diisobutylenes) 332 Questions Alkenes: A Multiple-Step Synthesis The Road from Butyl Alcohol to the 2-Methylhexenes Grignard Synthesis of an Alcohol Preparation of 2-Methyl-l-hexene and 2-Methyl-2-hexene 337 (A) Butyl Bromide 337 (B) Butylmagnesium Bromide 337 (C) 2-Methyl-2-hexanol 338 (D) 2-Methylhexenes 339 (E) Chromatographie Analysis of the 2-Methylhexenes 340 (F) NMR Analysis of the 2-Methylhexenes 340 Questions Hydration of Alkenes and Alkynes Hydration of Double Bonds Oxymercuration-Demercuration of Alkenes Hydration of Alkynes Reactions and Preparations 345 (A) Oxymercuration-Demercuration of 1-Hexene 345 (B) 2-Heptanone by Hydration of 1-Heptyne 346 Questions Glaser-Eglinton-Hayes Acetylene Coupling Introduction Mechanism of Acetylene Coupling Oxidative Coupling of 1-Ethynylcyclohexanol 351 Questions Oxidation of Alcohols to Ketones and Their Conversion to Amides Oxidation of Alcohols Transformation of the Carbonyl Group Preparations 354 (A) 2-Pentanone by Hypochlorite Oxidation 354 (B) Cyclohexanone by Hypochlorite Oxidation 355 (C) Cyclohexanone Oxime 356 (D) Beckmann Rearrangement of Cyclohexanone Oxime to Caprolactam 357 Questions 357

26 Addition Reactions of Aldehydes and Ketones 26.1 Carbonyl Addition Reactions 359 26.

9 26 Addition Reactions of Aldehydes and Ketones 26.1 Carbonyl Addition Reactions Equilibria and Rates in Carbonyl Reactions; Formation of 2-Furaldehyde and Cyclohexanone Semicarbazones Questions Reduction of the Carbonyl Group 27.1 Introduction Reduction by Sodium Borohydride: Diphenylmethanol (Benzhydrol) 363 Questions Diphenylacetylene via a Wittig Reaction 28.1 A Three-Step Synthetic Sequence The Wittig Reaction Bromination of Stilbene Diphenylacetylene Preparations 369 (A) ( >Stilbene 369 (B) Stilbene Dibromide 370 (C) Diphenylacetylene 370 Questions The Cannizzaro Reaction 29.1 Reactions of Aromatic Aldehydes Preparations and Reactions 372 (A) Benzyl Alcohol 372 (B) Benzoic Acid 373 Questions Esters 30.1 Esterification and Saponification Preparations and Reactions 378 (A) Butyl Acetate: Esterification of Acetic Acid 378 (B) Saponification of Butyl Acetate 379 (C) Methyl Benzoate 379 Questions Ionization of Carboxylic Acids 31.1 Introduction Inductive Effects Analysis of ph Versus Titer Data for pk 384

CONTENTS xiü 31.4 Measurement of the pk of a Carboxylic Acid 386 Questions 386 32 Friedel-Crafts Reactions 387 32.1 Alkylation of Benzene and Related Hydrocarbons 387 32.

10 CONTENTS xiü 31.4 Measurement of the pk of a Carboxylic Acid 386 Questions Friedel-Crafts Reactions Alkylation of Benzene and Related Hydrocarbons Friedel-Crafts Acylation Preparations 389 (A) p-methoxytetraphenylmethane 389 (B) 4-Acetylbiphenyl 390 Questions Nitration of Aromatic Compounds Mechanism of Nitration Preparations 394 (A) o- and p-nitrophenol 394 (B) Methyl m-nitrobenzoate 395 Questions Aldol Condensation Introduction Preparations 399 (A) Dibenzalacetone 399 (B) Tetraphenylcyclopentadienone 400 Questions The Benzilic Acid Rearrangement Introduction Preparation of Benzilic Acid 403 (A) From Benzil 403 (B) From Benzoin (Alternative Procedure) Reactions of Benzilic Acid 404 (A) Benzophenone from Benzilic Acid 404 (B) Acetylbenzilic Acid (a-acetoxyphenylacetic Acid) 405 (C) Methyl Benzilate 405 Questions Triphenylmethanol Triarylmethanols Preparation and Reactions of Triphenylmethanol 408 (A) Phenylmagnesium Bromide 408 (B) Triphenylmethanol 409 (C) Triphenylmetnyl Cation 410 Questions 410

xiv CONTENTS 37 The Pinacol-Pinacolone Rearrangement 412 37.1 Introduction 412 37.

11 xiv CONTENTS 37 The Pinacol-Pinacolone Rearrangement Introduction Preparations 412 (A) Benzopinacol by Photochemical Reduction 415 (B) Benzopinacolone 415 (C) Triphenylmethane by Alkaline Cleavage by Benzopinacolone 415 (D) Determination of Relative Migratory Aptitudes of Phenyl and p-tolyl 416 Questions Enamine Synthesis of a Diketone: 2-Acetylcyclohexanone The Enamine Reaction Preparation of 2-Acetylcyclohexanone 422 (A) Af-l-Cyclohexenylpyrrolidine (II) 422 (B) 2-Acetylcyclohexanone 423 Questions Wagner-Meerwein Rearrangements: Camphor from Camphene Introduction Preparation of Camphor 426 (A) Isobornyl Acetate 426 (B) Isoborneol 426 (C) Camphor by Oxidation of Isoborneol with Sodium Hypochlorite 426 Questions The Diels-Alder Reaction Introduction Diels-Alder Reactions of Benzoquinone Preparations 432 (A) TV-Phenylmaleimide 432 (B) Af-Phenyl-4-cyclohexene-l,2-dicarboximide (IV) 432 (C) AT-Phenyl-e«rfo-norbornene-5,6-dicarboximide 432 (D) 4-Cyclohexene-cw-l,2-dicarboxylic anhydride (I) 433 (E) Wo-Norbornene-«',s-5,6-dicarboxylic anhydride (V) 433 (F) 1,4-Dihydroxytriptycene 433 Questions Convergent Syntheses: Hexaphenylbenzene and Tetraphenyltriphenylene Convergent Synthesis 435

41.2 Hexaphenylbenzene 436 41.3 Tetraphenyltriphenylene 437 41.

12 41.2 Hexaphenylbenzene Tetraphenyltriphenylene Preparations 438 (A) Hexaphenylbenzene 438 (B) Phencyclone 439 (C) Tetraphenyltriphenylene 439 Questions Ferrocene and Acetylferrocene 42.1 Metallocenes Preparations 442 (A) Cyclopentadiene (Individual Preparation) (B) Cyclopentadiene (Group Preparation) 443 (C) Ferrocene (Dicyclopenadienyliron) 444 (D) Acetylferrocene 446 Questions Dyes and Indicators 43.1 Diazonium-Coupling Reactions Preparation ofazo Dyes 451 (A) Methyl Orange 451 (B) Para Red Phthalein and Sulfonphthalein Indicators Preparation ofo-cresol Red 456 Questions Solvatochromic Dyes 44.1 Merocyanin Dyes Theoretical Basis for Solvatochromism Synthesis of Merocyanin Dyes Preparation and Measurements 461 (A) 1,4-Dimethylpyridinium Iodide 461 (B) Merocyanin Dye 461 (C) Color Experiments 462 Questions Synthesis of Indigo 45.1 Introduction Indigo Synthesis Preparation and Reactions 465 (A) Indigo 465 (B) Indigo White and Vat Dyeing 465 Questions 466

xvi CONTENTS 46 Binaphthol 467 46.1 Oxidative Coupling of Phenols 467 46.2 Optical Properties of Binaphthol 469 46.

13 xvi CONTENTS 46 Binaphthol Oxidative Coupling of Phenols Optical Properties of Binaphthol Preparation of 2,2'-Binaphthol 469 Questions Carbene Additions with Phase-Transfer Catalysis Carbene Generation Phase-Transfer Catalysis Preparation of 7,7-Dichlorobicyclo[4.1.0]heptane 472 Questions 474 V COMPOUNDS OF MEDICINAL AND BIOLOGICAL INTEREST 48 Dilantin an Antiepileptic Drug by a Biomimetic Synthesis Introduction The Benzoin Condensation Oxidation of Benzoin to Benzil Condensation of Benzil with Urea to Form Dilantin 483 Questions Anaige sie s and Anesthetics Introduction Synthesis and Reactions of Acetylsalicylic Acid (Aspirin) 486 (A) Acetylsalicylic Acid 486 (B) Copper Aspirinate (Copper Acetylsalicylate) 487 (C) Methyl Salicylate p-ethoxyacetanilide (Phenacetin) p-aminobenzoic Acid (PABA) and Esters 489 (A) p-acetotoluidide 490 (B) p-acetamidobenzoic Acid 490 (C) p-aminobenzoic Acid 490 (D) Benzocaine 491 Questions Pheromones and Insect Repellents Chemical Communication Insect Repellents Preparation of Af.JV-Diethyl-m-Toluamide 494 (A) m-toluyl Chloride 494 (B) TV.JV-Diethyl-m-Toluamide (Off!) 494 Questions 495

14 CONTENTS XVÜ 51 Antimicrobial Agents: Sulfanilamide Introduction Synthesisof Sulfanilamide Preparation 499 (A) p-acetamidobenzenesulfonyl Chloride 499 (B) p-acetamidobenzenesulfonamide 499 (C) p-aminobenzenesulfonamide (Sulfanilamide) 500 Questions Artificial Sweeteners Introduction p-ethoxyphenylurea (Dulcin) 504 (A) Preparation by Cyanate Method 504 (B) Preparation by Urea Method 505 Questions Sugars Introduction Monosaccharide and Disaccharide Tests 507 (A) Test for Reducing Sugars 507 (B) Osazone Test 508 (C) Acetylation of Glucose 508 (D) Benzoylation of Glucose 508 Questions Biosynthesis of Alcohols Fermentation of Sugars Ethanol by Fermentation 514 Questions Peptides Biopolymers Structure Laboratory Synthesis of Polypeptides Preparation of Phthaloylglycylglyeine 519 (A) Phthaloylglycine 519 (B) Phthaloylglycyl Chloride 519 (C) Phthaloylglycylglycine 520 Questions Metalloporphyrins Introduction Absorption Spectroscopy of Porphyrins 523

15 XVÜi CONTENTS 56.3 Preparations 523 (A) a,/ß,y,8-tetraphenylporphyrin 523 (B) Copper(II) Tetraphenylporphyrin Complex 524 Questions 524 Appendixes 525 A. Tables of Physical Data 525 B. Preparation of Gas Chromatographie Columns 527 C. Expanded IR Correlations 529 D. Laboratory Reports 531 Index 535

Experiment Correlations for Lehman, Microscale Operational Organic Chemistry 2/e

Experiment Correlations for Lehman, Microscale Operational Organic Chemistry 2/e Preface Introduction Laboratory Safety Chemistry and the Environment The Effect of ph on a Food Preservative. Learning Basic Operations. Separating the Components of Panacetin. Extraction and Evaporation.