Download Experimental Organic

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
1.2
1.3
1.4
1.5
1.6
Laboratory Accidents
3
Fire and Explosion Hazards
4
Glassware Cuts
4
Corrosive Chemicals
5
Toxic Chemicals and Mutagens
6
The OSHA Laboratory Standard
6
General Remarks
2.1
2.2
2.3
2.4
2.5
2.6
Preparation Before the Laboratory
Laboratory Directions
14
In the Laboratory
15
Calculation of Yields
15
Samples and Reports
17
Disposal of Chemical Wastes
17
11
Basic Laboratory Operations
3.1
3.2
3.3
3.4
3.5
Apparatus
19
Cleaning and Drying Glassware
19
Apparatus with Interchangeable Ground-Glass Joints
Weighing and Measuring Reagents
23
Heat Sources
24
21
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
4
27
Accessory Operations
4.1
4.2
4.3
4.4
4.5
4.6
4.7
4.8
Drying Agents
29
Cooling Baths
31
Vacuum Pumps
32
Refluxing
36
Sample Addition
36
Gas Absorption Traps
Stirring
37
Rotatory Evaporation
37
39
SEPARATION AND PURIFICATION
OF ORGANIC COMPOUNDS
5
Simple and Fractional Distillation
5.1
5.2
5.3
5.4
Principles of Distillation
44
Fractional Distillation
51
Laboratory Practice
57
Representative Simple and Fractional Distillations
(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
6.2
6.3
6.4
Effect of Pressure on Boiling Point
Vacuum Pumps
71
Laboratory Practice
73
Representative Vacuum Distillations
(A) Purification of Methyl Benzoate
(B) Purification of Benzaldehyde
Questions
76
7
70
75
75
75
Steam Distillation
7.1 Principles of Steam Distillation
77
7.2 Distillation Temperature and Composition of Distillate
7.3 Laboratory Practice
80
66
VÜ
CONTENTS
7.4 Representative Steam Distillations
81
(A) Steam Distillation of Turpentine
81
(B) Separation of a Mixture by Steam Distillation
Questions
83
8
82
Melting Points, Crystallization, and Sublimation
Melting Points
84
Crystallization
89
Sublimation
97
Representative Procedures
98
(A) Melting Point of Mixtures
98
(B) Crystallization of Benzoic Acid from Water
(C) Crystallization of Acetanilide from Water
(D) Crystallization from a Flammable Solvent
(E) Small-Scale Recrystallization
101
(F) Selection of a Recrystallization Solvent
(G) Sublimation
102
Questions
102
84
8.1
8.2
8.3
8.4
9
98
100
100
101
Extraction with Solvents
9.1
9.2
9.3
9.4
9.5
9.6
9.7
Extraction of Solids
103
Extraction of Solutions
104
Multiple Extractions
106
Solubility Relationships
107
Laboratory Practice
110
Separation of Mixtures Containing Multiple Components
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
121
10 Chromatography
10.1 Introduction
122
10.2 Liquid-Solid Chromatography
123
10.3 Ion-Exchange Chromatography
126
10.4 Liquid-Liquid Chromatography
127
10.5 Gas-Liquid Chromatography
128
10.6 Laboratory Practice
130
10.7 Chromatographie Separations
142
(A) Separation of Ink Pigments by Thin-Layer
Chromatography
143
103
114
122
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
J I J IDENTIFICATION OF ORGANIC COMPOUNDS
11 Identification by Chemical Methods
Introduction
151
Preliminary Examination
152
Purification of the Unknown Sample
153
Physical Constants
153
Element Detection
155
Solubility Classification
159
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
178
11.8 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
Questions
206
151
11.1
11.2
11.3
11.4
11.5
11.6
11.7
12 Mass Spectrometry
12.1 Introduction
208
12.2 Generation of Ions
206
208
209
ix
CONTENTS
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
12.7 Sample Problem Solution
229
Questions
231
224
13 Infrared Spectroscopy
13.1 Introduction
234
13.2 Structure and Infrared Absorption Frequencies
236
13.3 Assignment of Principal Functional Groups
239
13.4 Spectroscopic Details for Selected Functional Groups
13.5 Infrared Sampling Techniques
250
Questions
253
234
246
14 Visible and Ultraviolet Spectroscopy
14.1 Introduction
254
14.2 Ultraviolet and Visible Spectroscopy
254
14.3 Ultraviolet and Visible Spectral Sampling Techniques
Questions
261
15 Nuclear Magnetic Resonance
254
261
263
15.1
15.2
15.3
15.4
15.5
15.6
15.7
Introduction
263
>H Chemical Shifts
264
Hydroxyl Protons and Proton Exchange
271
13
C Chemical Shifts
273
Signal Intensities
278
Spin-Spin Interactions
279
Representative Applications of 'H NMR in Structure
Elucidation
284
15.8 NMR Sampling Techniques
287
Questions
288
PREPARATION AND REACTIONS
OF TYPICAL ORGANIC COMPOUNDS
16 Isolation and Identification of Orange-Peel Oil
16.1 Isolation of Orange-Peel Oil
293
16.2 Identification of Orange-Peel Oil
295
(A) Chemical Analysis
295
(B) Determination of Boiling Point
298
(C) Spectroscopic Identification
298
Questions
298
293
CONTENTS
X
17 Free-Radical Halogenation
299
17.1
17.2
17.3
17.4
17.5
17.6
Mechanism of Free-Radical Chlorination
299
Chlorination by Means of Sulfuryl Chloride and AIBN
300
Energetics of Halogenation
301
Selectivity of Halogenations
302
Substituent Effects
303
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
307
18 Conversion of Alcohols to Alkyl Halides
309
18.1 Preparation of Alkyl Halides
309
18.2 Reactions of Alkyl Halides
311
18.3 Preparations
312
(A) Butyl Bromide
312
(B) Cyclohexyl Chloride
314
(C) tert-Butyl Chloride
315
Questions
316
19 Second-Order Nucleophilic Substitution
317
19.1 Replacement Reactions
317
19.2 Stereochemistry and Kinetics
318
19.3 Nucleophilicity
318
19.4 Substrate Structure
319
19.5 Solvent
319
19.6 Preparation of Butyl Iodide
320
Questions
320
20 Chemical Kinetics: Solvolysis of tert-Butyl Chloride
321
20.1
20.2
20.3
20.4
First-Order Kinetics
321
Effect of Solvent on Rate of Solvolysis
321
Laboratory Practice
324
Measurement of the SN1 Reaction Rate of tert-Butyl
Chloride
325
Questions
326
21 Alkenes: El and E2 Reactions
21.1
21.2
21.3
21.4
Sources of Alkenes
327
Carbocation Rearrangements
328
Dimerization of Isobutylene (2-Methylpropene)
Reactions of Alkenes
330
327
329
xi
CONTENTS
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)
Questions
332
332
22 Alkenes: A Multiple-Step Synthesis
334
22.1 The Road from Butyl Alcohol to the 2-Methylhexenes
22.2 Grignard Synthesis of an Alcohol
336
22.3 Preparation of 2-Methyl-l-hexene and 2-Methyl-2-hexene
(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
(F) NMR Analysis of the 2-Methylhexenes
340
Questions
342
23 Hydration of Alkenes and Alkynes
334
337
340
343
23.1
23.2
23.3
23.4
Hydration of Double Bonds
343
Oxymercuration-Demercuration of Alkenes
344
Hydration of Alkynes
345
Reactions and Preparations
345
(A) Oxymercuration-Demercuration of 1-Hexene
345
(B) 2-Heptanone by Hydration of 1-Heptyne
346
Questions
347
24 Glaser-Eglinton-Hayes Acetylene Coupling
24.1 Introduction
349
24.2 Mechanism of Acetylene Coupling
350
24.3 Oxidative Coupling of 1-Ethynylcyclohexanol
Questions
352
349
351
25 Oxidation of Alcohols to Ketones and Their
Conversion to Amides
25.1 Oxidation of Alcohols
353
25.2 Transformation of the Carbonyl Group
354
25.3 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
353
26 Addition Reactions of Aldehydes and Ketones
26.1 Carbonyl Addition Reactions
359
26.2 Equilibria and Rates in Carbonyl Reactions; Formation
of 2-Furaldehyde and Cyclohexanone Semicarbazones
Questions
361
27 Reduction of the Carbonyl Group
27.1 Introduction
362
27.2 Reduction by Sodium Borohydride: Diphenylmethanol
(Benzhydrol)
363
Questions
365
28 Diphenylacetylene via a Wittig Reaction
28.1
28.2
28.3
28.4
28.5
A Three-Step Synthetic Sequence
The Wittig Reaction
367
Bromination of Stilbene
368
Diphenylacetylene
368
Preparations
369
(A) (£>Stilbene
369
(B) Stilbene Dibromide
370
(C) Diphenylacetylene
370
Questions
370
366
29 The Cannizzaro Reaction
29.1 Reactions of Aromatic Aldehydes
29.2 Preparations and Reactions
372
(A) Benzyl Alcohol
372
(B) Benzoic Acid
373
Questions
374
371
30 Esters
30.1 Esterification and Saponification
375
30.2 Preparations and Reactions
378
(A) Butyl Acetate: Esterification of Acetic Acid
(B) Saponification of Butyl Acetate
379
(C) Methyl Benzoate
379
Questions
380
31 Ionization of Carboxylic Acids
31.1 Introduction
382
31.2 Inductive Effects
383
31.3 Analysis of pH Versus Titer Data for pK
384
378
xiü
CONTENTS
31.4 Measurement of the pK of a Carboxylic Acid
Questions
386
386
32 Friedel-Crafts Reactions
387
32.1 Alkylation of Benzene and Related Hydrocarbons
32.2 Friedel-Crafts Acylation
388
32.3 Preparations
389
(A) p-Methoxytetraphenylmethane
389
(B) 4-Acetylbiphenyl
390
Questions
391
387
33 Nitration of Aromatic Compounds
392
33.1 Mechanism of Nitration
392
33.2 Preparations
394
(A) o- and p-Nitrophenol
394
(B) Methyl m-Nitrobenzoate
395
Questions
395
34 Aldol Condensation
34.1 Introduction
397
34.2 Preparations
399
(A) Dibenzalacetone
399
(B) Tetraphenylcyclopentadienone
Questions
400
397
400
35 The Benzilic Acid Rearrangement
401
35.1 Introduction
401
35.2 Preparation of Benzilic Acid
403
(A) From Benzil
403
(B) From Benzoin (Alternative Procedure)
403
35.3 Reactions of Benzilic Acid
404
(A) Benzophenone from Benzilic Acid
404
(B) Acetylbenzilic Acid (a-Acetoxyphenylacetic Acid)
(C) Methyl Benzilate
405
Questions
405
405
36 Triphenylmethanol
36.1 Triarylmethanols
406
36.2 Preparation and Reactions of Triphenylmethanol
(A) Phenylmagnesium Bromide
408
(B) Triphenylmethanol
409
(C) Triphenylmetnyl Cation
410
Questions
410
406
408
xiv
CONTENTS
37 The Pinacol-Pinacolone Rearrangement
412
37.1 Introduction
412
37.2 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
418
38 Enamine Synthesis of a Diketone:
2-Acetylcyclohexanone
38.1 The Enamine Reaction
420
38.2 Preparation of 2-Acetylcyclohexanone
(A) Af-l-Cyclohexenylpyrrolidine (II)
(B) 2-Acetylcyclohexanone
423
Questions
423
420
422
422
39 Wagner-Meerwein Rearrangements: Camphor
from Camphene
424
39.1 Introduction
421
39.2 Preparation of Camphor
426
(A) Isobornyl Acetate
426
(B) Isoborneol
426
(C) Camphor by Oxidation of Isoborneol with Sodium
Hypochlorite
426
Questions
427
40 The Diels-Alder Reaction
428
40.1 Introduction
428
40.2 Diels-Alder Reactions of Benzoquinone
430
40.3 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
434
41 Convergent Syntheses: Hexaphenylbenzene
and Tetraphenyltriphenylene
41.1 Convergent Synthesis
435
435
41.2 Hexaphenylbenzene
436
41.3 Tetraphenyltriphenylene
437
41.4 Preparations
438
(A) Hexaphenylbenzene
438
(B) Phencyclone
439
(C) Tetraphenyltriphenylene
439
Questions
440
42 Ferrocene and Acetylferrocene
42.1 Metallocenes
441
42.2 Preparations
442
(A) Cyclopentadiene (Individual Preparation)
(B) Cyclopentadiene (Group Preparation)
443
(C) Ferrocene (Dicyclopenadienyliron)
444
(D) Acetylferrocene
446
Questions
447
43 Dyes and Indicators
43.1 Diazonium-Coupling Reactions
449
43.2 Preparation ofAzo Dyes
451
(A) Methyl Orange
451
(B) Para Red
452
43.3 Phthalein and Sulfonphthalein Indicators
43.4 Preparation ofo-Cresol Red
456
Questions
457
44
453
Solvatochromic Dyes
44.1
44.2
44.3
44.4
Merocyanin Dyes
458
Theoretical Basis for Solvatochromism
459
Synthesis of Merocyanin Dyes
460
Preparation and Measurements
461
(A) 1,4-Dimethylpyridinium Iodide
461
(B) Merocyanin Dye
461
(C) Color Experiments
462
Questions
462
45 Synthesis of Indigo
45.1 Introduction
463
45.2 Indigo Synthesis
464
45.3 Preparation and Reactions
465
(A) Indigo
465
(B) Indigo White and Vat Dyeing
Questions
466
465
xvi
CONTENTS
46 Binaphthol
46.1 Oxidative Coupling of Phenols
46.2 Optical Properties of Binaphthol
46.3 Preparation of 2,2'-Binaphthol
Questions
469
467
467
469
469
47 Carbene Additions with Phase-Transfer Catalysis
47.1 Carbene Generation
470
47.2 Phase-Transfer Catalysis
471
47.3 Preparation of 7,7-Dichlorobicyclo[4.1.0]heptane
Questions
474
470
472
V COMPOUNDS OF MEDICINAL
AND BIOLOGICAL INTEREST
48 Dilantin—an Antiepileptic Drug by a
Biomimetic Synthesis
48.1 Introduction
478
48.2 The Benzoin Condensation
478
48.3 Oxidation of Benzoin to Benzil
481
48.4 Condensation of Benzil with Urea to Form Dilantin
Questions
484
478
483
49 Anaige sie s and Anesthetics
49.1 Introduction
485
49.2 Synthesis and Reactions of Acetylsalicylic Acid (Aspirin)
(A) Acetylsalicylic Acid
486
(B) Copper Aspirinate (Copper Acetylsalicylate)
487
(C) Methyl Salicylate
487
49.3 p-Ethoxyacetanilide (Phenacetin)
488
49.4 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
491
50 Pheromones and Insect Repellents
50.1 Chemical Communication
492
50.2 Insect Repellents
493
50.3 Preparation of Af.JV-Diethyl-m-Toluamide
494
(A) m-Toluyl Chloride
494
(B) TV.JV-Diethyl-m-Toluamide (Off!)
494
Questions
495
485
486
492
XVÜ
CONTENTS
51 Antimicrobial Agents: Sulfanilamide
496
51.1 Introduction
496
51.2 Synthesisof Sulfanilamide
498
51.3 Preparation
499
(A) p-Acetamidobenzenesulfonyl Chloride
499
(B) p-Acetamidobenzenesulfonamide
499
(C) p-Aminobenzenesulfonamide (Sulfanilamide)
Questions
500
52 Artificial Sweeteners
500
502
52.1 Introduction
502
52.2 p-Ethoxyphenylurea (Dulcin)
504
(A) Preparation by Cyanate Method
504
(B) Preparation by Urea Method
505
Questions
505
53 Sugars
506
53.1 Introduction
506
53.2 Monosaccharide and Disaccharide Tests
(A) Test for Reducing Sugars
507
(B) Osazone Test
508
(C) Acetylation of Glucose
508
(D) Benzoylation of Glucose
508
Questions
511
507
54 Biosynthesis of Alcohols
54.1 Fermentation of Sugars
54.2 Ethanol by Fermentation
Questions
515
512
512
514
55 Peptides—Biopolymers
55.1 Structure
516
55.2 Laboratory Synthesis of Polypeptides
55.3 Preparation of Phthaloylglycylglyeine
(A) Phthaloylglycine
519
(B) Phthaloylglycyl Chloride
519
(C) Phthaloylglycylglycine
520
Questions
520
516
517
519
56 Metalloporphyrins
56.1 Introduction
521
56.2 Absorption Spectroscopy of Porphyrins
521
523
XVÜi
CONTENTS
56.3 Preparations
523
(A) a,/ß,y,8-Tetraphenylporphyrin
523
(B) Copper(II) Tetraphenylporphyrin Complex
Questions
524
524
Appendixes
A.
B.
C.
D.
Tables of Physical Data
525
Preparation of Gas Chromatographie Columns
Expanded IR Correlations
529
Laboratory Reports
531
Index
525
527
535