George Mason University Organic Chemistry Biodiesel Lab Conclusion

Organic Chemistry Lab II Conclusions. This is just like last time and you don’t need to write an outline and explanation just answer the questions.

https://drive.google.com/drive/folders/1ix_8HZRdtn…

https://drive.google.com/drive/folders/14GhXzYyHPy…

https://drive.google.com/drive/folders/1vK1s0upA7P…

https://drive.google.com/drive/folders/1WqbaR_ecnA…

•
Biodiesel Lab Conclusion
1. The synthesis of biodiesel can be classified under what type of organic reaction?
2. Can all esters be considered as biodiesel? Why?
3. Under what conditions does transesterification tend to favor the product?
4. What alternate synthetic route could produce FAMEs? Why is this route less preferred than
transesterification?
5. Why does the exact nature of the oil matter less in the making of FAMES?
•
Aldehyde/Ketone Analysis lab Conclusions
1. Which qualitative analysis test from this module can help distinguish between different kinds of
ketones? Can this same test give a positive result for 4-methylacetophenone? Why?
2. What is the reduced species in the Tollens test? What visual observation will indicate a positive result in
the test tube?
3. If an unknown compound undergoes oxidation during the chromic acid test, which functional group is
present? What color change should you observe in the test tube for confirmation?
4. An unknown substance is found to be soluble in water and gives a positive 2,4- DNP test. If you observe
a yellow color after performing the iodoform test, what specific functional group must be present in the
unknown?
5. Is it possible for a single molecule to test true positive in all the qualitative assays described in this
module? Why or why not?
•
Aldol Condensation Conclusions
1. Why was the acetone the limiting reagent for this lab? What would have likely happened if
benzaldehyde was the limiting reagent instead?
2. What is the driving force for this reaction? What physical property also assists in keeping the
equilibrium headed towards product?
3. The same physical property that helps drive the reaction to completion can also stall out the reaction
before it starts. What do we do in the procedure that helps minimize this concern?
4. What is this reaction classified as?
5. The protocol says that, after adding in all the reactants, stir for an additional 15 minutes. A student
stirred for only 8 minutes; took a sample and did something; and then, correctly, stopped and proceeded
with isolating the product. What something did the student do that gave such confidence and accuracy?
•
UV Conclusions
1. If the extinction coefficient can be calculated from a single absorbance measurement at a known
concentration of a compound, why is a calibration curve necessary, even if the measured absorbance is
below 1?
2. Why should absorbance be less than 2? Please explain in terms of light transmittance.
3. Why is a linear calibration curve important? Couldn’t interpolation be used to predict values within the
calibration range?
4. Acetaldehyde shows two UV bands, one with a λmax of 289 nm (ε = 12) and one with a λmax of
182 nm (ε = 10,000). Which one is the n -> π* transition and which is the π -> π* transition? Explain
your reasoning.
5. Perhaps it is unsurprising that cyclohexane and ethanol are reasonable UV solvents, whereas toluene is
not. Explain why that is.
7 × 10 SPINE: 0.75 FLAPS: 0
Laboratory Techniques in Organic Chemistry, FOURTH EDITION
Supporting Inquiry-Driven Experiments
Mohrig
Alberg
100
Hofmeister
Hammond
Laboratory Techniques in Organic Chemistry
Freeman Custom Publishing’s newest offering provides instructors with a diverse database
of extensive experiments to choose from–all in an easy-to-use, searchable online system.
FOURTH
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80
% Transmittance
Schatz
Jerry R. Mohrig, Carleton College
David G. Alberg, Carleton College
Gretchen E. Hofmeister, Carleton College
Paul F. Schatz, University of Wisconsin–Madison
Christina Noring Hammond, Vassar College
60
40
20
0
4000
3500
3000
2500
2000
1800
1600
1400
1200
1000
800
600
Wavenumber (cm-1)
CH3O
H
HO
H
H
C
C
CH 2
H
H
H
Eugenol
(Oil of Cloves)
7
6
ppm
5
4
Laboratory Techniques
in Organic Chemistry
FOURTH EDITION
Supporting Inquiry-Driven Experiments
FREEMAN
Jerry R. Mohrig
David G. Alberg
Gretchen E. Hofmeister
Paul F. Schatz
Christina Noring Hammond
3
Chemical resistance of common types of gloves to various compounds
Glove type
2.0 mL
1.5 mL
1.0 mL
Compound
Neoprene
Nitrile
Latex
Acetone
Chloroform
Dichloromethane
Diethyl ether
Ethanol
Ethyl acetate
Hexane
Hydrogen peroxide
Methanol
Nitric acid (conc.)
Sodium hydroxide
Sulfuric acid (conc.)
Toluene
Good
Good
Fair
Very good
Very good
Good
Excellent
Excellent
Very good
Good
Very good
Good
Fair
Fair
Poor
Poor
Good
Good
Poor
Excellent
Good
Fair
Poor
Good
Poor
Fair
Good
Poor
Poor
Poor
Good
Fair
Poor
Good
Fair
Poor
Excellent
Poor
Poor
0.5 mL
Common organic solvents
0.1 mL
Name
Boiling
point (°C)
Density
(g / mL)
Dielectric
constant
Miscible
with H2O
Acetone (2-propanone)
Dichloromethane
Diethyl ether
Ethanol (95% aq. azeotrope)
Ethanol (anhydrous)
Ethyl acetate
Hexane
Methanol
Pentane
2-Propanol (isopropyl alcohol)
Toluene
56.5
40
35
78
78.5
77
69
65
36
82.5
111
0.792
1.326
0.713
0.816
0.789
0.902
0.660
0.792
0.626
0.785
0.866
21
9.1
4.3
27
25
6.0
1.9
33
1.8
18
2.4
yes
no
no
yes
yes
slightly
no
yes
no
yes
no
Selected approximate pKa values
Name
Formula
Sulfuric acid
1
2
3
4
Name
Formula
pKa
10
H2SO4
25
Ammonium
NH41
Aqueous mineral
H3O1
acids
22
Protonated
amines
R3NH1
10
O
,
Carboxylic acids RCOH
5
Alcohols
ROH
16
Bicarbonate
6
Water
H2O
16
10
Acetone
HCO32
OH
Phenols
cm
pKa
5
6
7
8
9
O
10
11
,
CH3CCH3 19
12
13
14
15
*Molar masses quoted to the number of
significant figures given here can be
regarded as typical of most naturally
occurring samples.
103
Lr
262.1
104
Rf
106
Sg
58
Ce
140.12
90
Th
232.04
57
La
138.91
89
Ac
227.03
74
W
183.85
105
Db
73
Ta
180.95
42
Mo
95.94
91
Pa
231.04
59
Pr
140.91
107
Bh
75
Re
186.2
43
Tc
98.91
92
U
238.03
60
Nd
144.24
108
Hs
76
Os
190.2
44
Ru
101.07
93
Np
237.05
61
Pm
146.92
109
Mt
77
Ir
192.2
45
Rh
102.91
27
Co
58.93
94
Pu
239.05
62
Sm
150.35
110
Uun
78
Pt
195.09
46
Pd
106.4
28
Ni
58.71
95
Am
241.06
63
Eu
151.96
111
Uuu
79
Au
196.97
47
Ag
107.87
29
Cu
63.54
96
Cm
247.07
64
Gd
157.25
112
Uub
80
Hg
200.59
48
Cd
112.40
30
Zn
65.37
97
Bk
249.08
65
Tb
158.92
113
Uut
81
Tl
204.37
49
In
114.82
31
Ga
69.72
98
Cf
251.08
66
Dy
162.50
82
Pb
207.19
50
Sn
118.69
32
Ge
72.59
99
Es
254.09
67
Ho
164.93
Metals
83
Bi
208.98
51
Sb
121.75
33
As
74.92
15
P
30.97
100
Fm
257.10
68
Er
167.26
Metalloids
84
Po
210
52
Te
127.60
34
Se
78.96
16
S
32.06
101
Md
258.10
69
Tm
168.93
Nonmetals
85
At
210
53
I
126.90
35
Br
79.91
17
Cl
35.45
102
No
255
70
Yb
173.04
86
Rn
222
54
Xe
131.30
36
Kr
83.80
18
Ar
39.95
88
Ra
226.03
72
Hf
178.49
41
Nb
92.91
26
Fe
55.85
14
Si
28.09
87
Fr
223
71
Lu
174.97
40
Zr
91.22
25
Mn
54.94
13
Al
26.98
7
12
IIB
56
Ba
137.34
11
IB
55
Cs
132.91
10
6
39
Y
88.91
24
Cr
52.00
9
VIIIB
38
Sr
87.62
23
V
50.94
8
37
Rb
85.47
22
Ti
47.88
7
VIIB
5
21
Sc
44.96
6
VIB
20
Ca
40.08
5
VB
19
K
39.10
4
IVB
4
3
IIIB
9
F
19.00
12
Mg
24.31
8
O
16.00
11
Na
22.99
7
N
14.01
18
VIII
VIIIA
3
6
C
12.01
17
VII
VIIA
10
Ne
20.18
5
B
10.81
16
VI
VIA
4
Be
9.01
15
V
VA
3
Li
6.94
14
IV
IVA
2
13
III
IIIA
2
He
4.00
PERIODIC TABLE OF THE ELEMENTS
1
H
1.0079
2
II
IIA
1
1
I
IA
Actinides
Lanthanides
Laboratory Techniques in
Organic Chemistry
Supporting Inquiry-Driven Experiments
Fourth Edition
JERRY R. MOHRIG
Carleton College
DAVID G. ALBERG
Carleton College
GRETCHEN E. HOFMEISTER
Carleton College
PAUL F. SCHATZ
University of Wisconsin, Madison
CHRISTINA NORING HAMMOND
Vassar College
W. H. Freeman and Company
A Macmillan Higher Education Company
Publisher: Jessica Fiorillo
Acquisitions Editor: Bill Minick
Assistant Editor/Development Editor: Courtney Lyons
Associate Director of Marketing: Debbie Clare
Marketing Assistant: Samantha Zimbler
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Project Management/Composition: Ed Dionne, MPS Ltd.
Printing and Binding: Quad Graphics
Library of Congress Control Number: 2013955847
ISBN-13: 978-1-4641-3422-7
ISBN-10: 1-4641-3422-7
© 2014, 2010, 2007, 2003 by W. H. Freeman and Company
All rights reserved
Printed in the United States of America
First Printing
W. H. Freeman and Company
41 Madison Avenue, New York, NY 10010
Houndmills, Basingstoke, RG21 6XS, England
www.whfreeman.com
Contents
Preface
PART 1
xiii
Introduction to the Organic Laboratory
1
ESSAY—The Role of the Laboratory
1
1
3
Safety in the Laboratory
1.1
1.2
1.3
1.4
1.5
1.6
1.7
1.8
2
Green Chemistry
2.1
2.2
2.3
3
General Safety Information 4
Preventing Chemical Exposure 5
Preventing Cuts and Burns 8
Preventing Fires and Explosions 9
What to Do if an Accident Occurs 11
Chemical Toxicology 13
Identifying Chemicals and Understanding Chemical Hazards
Handling Laboratory Waste 20
Further Reading 21
Questions 21
22
The Principles of Green Chemistry 23
Green Principles Applied to Industrial Processes 24
Green Principles Applied to Academic Laboratories 28
Further Reading 31
Questions 32
Laboratory Notebooks and Prelab Information
3.1
3.2
3.3
PART 2
14
32
The Laboratory Notebook 33
Calculation of the Percent Yield 35
Sources of Prelaboratory Information 36
Further Reading 39
Questions 39
Carrying Out Chemical Reactions
41
ESSAY—Learning to Do Organic Chemistry
41
4
44
Laboratory Glassware
4.1
4.2
4.3
4.4
Desk Equipment 45
Miniscale Standard Taper Glassware 45
Microscale Glassware 47
Cleaning and Drying Laboratory Glassware
Questions 51
50
vi
5
Contents
Measurements and Transferring Reagents
5.1
5.2
5.3
5.4
5.5
52
Using Electronic Balances 52
Transferring Solids to a Reaction Vessel 54
Measuring Volume and Transferring Liquids 55
Measuring Temperature 62
Measurement Uncertainty and Error Analysis 64
Further Reading 72
Questions 72
6 Heating and Cooling Methods
6.1
6.2
6.3
6.4
6.5
7
81
Setting Up Organic Reactions
7.1
7.2
7.3
7.4
7.5
7.6
8
Preventing Bumping of Liquids 73
Conventional Heating Devices 74
Heating with Laboratory Microwave Reactors
Cooling Methods 85
Laboratory Jacks 85
Further Reading 86
Questions 86
73
Refluxing a Reaction Mixture 87
Addition of Reagents During a Reaction 89
Anhydrous Reaction Conditions 90
Inert Atmosphere Reaction Conditions 93
Transfer of Liquids by Syringe Without Exposure to Air
Removal of Noxious Vapors 103
Further Reading 106
Questions 106
86
101
Computational Chemistry
8.1
8.2
8.3
8.4
8.5
107
Picturing Molecules on the Computer 107
Molecular Mechanics Method 109
Quantum Mechanics Methods: Ab Initio, Semiempirical, and DFT
Which Computational Method Is Best? 121
Sources of Confusion and Common Pitfalls 121
Further Reading 124
Questions 124
115
PART 3 Basic Methods for Separation, Purification,
and Analysis
127
ESSAY—Intermolecular Forces in Organic Chemistry
127
9
132
Filtration
9.1
9.2
9.3
9.4
9.5
Filtering Media 132
Gravity Filtration 134
Small-Scale Gravity Filtration 135
Vacuum Filtration 137
Other Liquid-Solid and Liquid-Liquid Separation Techniques
140
vii
Contents
9.6
10
Sources of Confusion and Common Pitfalls
Questions 142
140
Extraction
10.1
10.2
10.3
10.4
10.5
10.6
142
Understanding How Extraction Works 143
Changing Solubility with Acid-Base Chemistry 147
Doing Extractions 149
Miniscale Extractions 152
Summary of the Miniscale Extraction Procedure 155
Microscale Extractions 155
10.6a Equipment and Techniques Common to Microscale Extractions 156
10.6b Microscale Extractions with an Organic Phase Less Dense Than Water 158
10.6c Microscale Extractions with an Organic Phase More Dense Than Water 160
10.7
11
161
Drying Organic Liquids and Recovering Reaction Products
11.1
11.2
11.3
11.4
12
Sources of Confusion and Common Pitfalls
Questions 163
Drying Agents 163
Methods for Separating Drying Agents from Organic Liquids 166
Sources of Confusion and Common Pitfalls 168
Recovery of an Organic Product from a Dried Extraction Solution 169
Questions 173
Boiling Points and Distillation
12.1
12.2
12.3
163
Determination of Boiling Points 174
Distillation and Separation of Mixtures
Simple Distillation 180
173
176
12.3a Miniscale Distillation 180
12.3b Miniscale Short-Path Distillation 183
12.3c Microscale Distillation Using Standard Taper 14/10 Apparatus 184
12.3d Microscale Distillation Using Williamson Apparatus 187
12.4
12.5
12.6
12.7
12.8
Fractional Distillation 188
Azeotropic Distillation 193
Steam Distillation 194
Vacuum Distillation 197
Sources of Confusion and Common Pitfalls
Further Reading 205
Questions 205
203
13 Refractometry
13.1
13.2
13.3
13.4
14
The Refractive Index 206
The Refractometer 208
Determining a Refractive Index 208
Sources of Confusion and Common Pitfalls
Questions 211
206
211
Melting Points and Melting Ranges
14.1
14.2
Melting-Point Theory 212
Apparatus for Determining Melting Ranges 213
211
viii
Contents
14.3
14.4
14.5
14.6
Determining Melting Ranges 215
Summary of Melting-Point Technique 217
Using Melting Points to Identify Compounds 218
Sources of Confusion and Common Pitfalls 219
Further Reading 220
Questions 220
15 Recrystallization
15.1
15.2
15.3
15.4
15.5
15.6
15.7
15.8
16
221
Introduction to Recrystallization 221
Summary of the Recrystallization Process 223
Carrying Out Successful Recrystallizations 224
How to Select a Recrystallization Solvent 225
Miniscale Procedure for Recrystallizing a Solid 228
Microscale Recrystallization 231
Microscale Recrystallization Using a Craig Tube 232
Sources of Confusion and Common Pitfalls 234
Questions 235
Sublimation
16.1
16.2
16.3
16.4
236
Sublimation of Solids 236
Assembling the Apparatus for a Sublimation 237
Carrying Out a Microscale Sublimation 238
Sources of Confusion and Common Pitfalls 239
Questions 239
17 Optical Activity and Enantiomeric Analysis
17.1
17.2
17.3
17.4
17.5
PART 4
Mixtures of Optical Isomers: Separation/Resolution
Polarimetric Techniques 243
Analyzing Polarimetric Readings 247
Modern Methods of Enantiomeric Analysis 248
Sources of Confusion and Common Pitfalls 250
Questions 251
240
240
Chromatography
253
ESSAY—Modern Chromatographic Separations
253
18 Thin-Layer Chromatography
255
18.1
18.2
18.3
18.4
18.5
18.6
18.7
18.8
18.9
Plates for Thin-Layer Chromatography 256
Sample Application 257
Development of a TLC Plate 260
Visualization Techniques 261
Analysis of a Thin-Layer Chromatogram 263
Summary of TLC Procedure 264
How to Choose a Developing Solvent When None Is Specified
Using TLC Analysis in Synthetic Organic Chemistry 267
Sources of Confusion and Common Pitfalls 267
265
ix
Contents
Further Reading 269
Questions 269
19
Liquid Chromatography
19.1
19.2
19.3
19.4
19.5
270
Adsorbents 270
Elution Solvents 272
Determining the Column Size 273
Flash Chromatography 275
Microscale Liquid Chromatography 281
19.5a Preparation and Elution of a Microscale Column 281
19.5b Preparation and Elution of a Williamson Microscale Column 283
19.6
19.7
19.8
20
Summary of Liquid Chromatography Procedures 285
Sources of Confusion and Common Pitfalls 285
High-Performance Liquid Chromatography 287
Further Reading 291
Questions 291
Gas Chromatography
20.1
20.2
20.3
20.4
20.5
20.6
20.7
20.8
PART 5
Instrumentation for GC 293
Types of Columns and Liquid Stationary Phases 294
Detectors 296
Recorders and Data Stations 297
GC Operating Procedures 299
Sources of Confusion and Common Pitfalls 303
Identification of Compounds Shown on a Chromatogram
Quantitative Analysis 305
Further Reading 308
Questions 308
291
304
SpectroMETRic Methods
309
ESSAY—The Spectrometric Revolution
309
21
311
Infrared Spectroscopy
21.1
21.2
21.3
21.4
21.5
21.6
21.7
21.8
21.9
21.10
21.11
IR Spectra 311
Molecular Vibrations 311
IR Instrumentation 316
Operating an FTIR Spectrometer 319
Sample Preparation for Transmission IR Spectra 319
Sample Preparation for Attenuated Total Reflectance (ATR) Spectra
Interpreting IR Spectra 325
IR Peaks of Major Functional Groups 330
Procedure for Interpreting an IR Spectrum 338
Case Study 339
Sources of Confusion and Common Pitfalls 341
Further Reading 344
Questions 344
323
x
Contents
22 Nuclear Magnetic Resonance Spectroscopy
22.1
22.2
22.3
22.4
22.5
22.6
22.7
22.8
22.9
22.10
22.11
23
NMR Instrumentation 350
Preparing Samples for NMR Analysis 353
Summary of Steps for Preparing an NMR Sample 357
Interpreting 1H NMR Spectra 357
How Many Types of Protons Are Present? 357
Counting Protons (Integration) 358
Chemical Shift 359
Quantitative Estimation of Chemical Shifts 366
Spin-Spin Coupling (Splitting) 377
Sources of Confusion and Common Pitfalls 391
Two Case Studies 398
Further Reading 405
Questions 405
C and Two-Dimensional NMR Spectroscopy
408
13
23.1
23.2
23.3
23.4
23.5
23.6
24
348
C NMR Spectra 408
C Chemical Shifts 412
Quantitative Estimation of 13C Chemical Shifts 417
Determining Numbers of Protons on Carbon Atoms—APT and DEPT
Case Study 429
Two-Dimensional Correlated Spectroscopy (2D COSY) 431
Further Reading 435
Questions 435
13
13
Mass Spectrometry
24.1
24.2
24.3
24.4
24.5
24.6
24.7
441
Mass Spectrometers 442
Mass Spectra and the Molecular Ion 446
High-Resolution Mass Spectrometry 450
Mass Spectral Libraries 451
Fragment Ions 453
Case Study 459
Sources of Confusion 461
Further Reading 462
Questions 462
25 Ultraviolet and Visible Spectroscopy
25.1
25.2
25.3
25.4
26
427
UV-VIS Spectra and Electronic Excitation 466
UV-VIS Instrumentation 471
Preparing Samples and Operating the Spectrometer
Sources of Confusion and Common Pitfalls 474
Further Reading 475
Questions 475
Integrated Spectrometry Problems
465
472
476
xi
Contents
PART 6 Designing and carrying out
organic experiments
485
ESSAY—Inquiry-Driven Lab Experiments
485
27
488
Designing Chemical Reactions
27.1 Reading Between the Lines: Carrying Out Reactions Based on
Literature Procedures 488
27.2
Modifying the Scale of a Reaction 494
27.3
Case Study: Synthesis of a Solvatochromic Dye 497
27.4 Case Study: Oxidation of a Secondary Alcohol to a Ketone 499
Further Reading 500
28 Using the Literature of Organic Chemistry
28.1
28.2
28.3
Index
The Literature of Organic Chemistry 501
Searching the Literature of Organic Chemistry
Planning a Multistep Synthesis 506
501
504
511
xiii
Contents
Preface
In preparing this Fourth Edition of Laboratory Techniques in Organic Chemistry, we have
maintained our emphasis on the fundamental techniques that students encounter in
the organic chemistry laboratory. We have also expanded our emphasis on the criticalthinking skills that students need to successfully carry out inquiry-driven experiments.
The use of guided-inquiry and design-based experiments and projects is arguably the most
important recent development in the teaching of the undergraduate organic chemistry lab,
and it provides the most value added for our students.
Organic chemistry is an experimental science, and students learn its process in the
laboratory. Our primary goal should be to teach students how to carry out well-designed
experiments and draw reasonable conclusions from their results—a process at the heart of
science. We should work to find opportunities that engage students in addressing questions whose answers come from their experiments, in an environment where they can
succeed. These opportunities should be designed to catch students’ interest, transforming
them from passive spectators to active participants. A well-written and comprehensive
textbook on the techniques of experimental organic chemistry is an important asset in
reaching these goals.
Changes in the Fourth Edition
The Fourth Edition of Laboratory Techniques in Organic Chemistry builds on our strengths in basic lab techniques and spectroscopy, and includes a number of new features. To make it easier
for students to locate the content relevant to their experiments, icons distinguish the techniques specific to each of the three common types of lab glassware — miniscale standard taper,
microscale standard taper, and Williamson glassware — and also highlight safety concerns.
  
  
Sections on microwave reactors, flash chromatography, green chemistry, handling airsensitive reagents, and measurement uncertainty and error analysis have been added or
updated. The newly added Part 6 emphasizes the skills students need to carry out inquirydriven experiments, especially designing and carrying out experiments based on literature
sources. Many sections concerning basic techniques have been modified and reorganized
to better meet the practical needs of students as they encounter laboratory work. Additional questions have also been added to a number of chapters to help solidify students’
understanding of the techniques.
Short essays provide context for each of the six major parts of the Fourth Edition,
on topics from the role of the laboratory to the spectrometric revolution. The essay
“Intermolecular Forces in Organic Chemistry” provides the basis for subsequent discussions on organic separation and purification techniques, and the essay “Inquiry-Driven Lab
Experiments” sets the stage for using guided-inquiry and design-based experiments.
Rewritten sections on sources of confusion and common pitfalls help students avoid and
solve technical problems that could easily discourage them if they did not have this practical support. We believe that these features provide an effective learning tool for students
of organic chemistry.
xiii
xiv
Contents
Preface
Who Should Use This Book?
The book is intended to serve as a laboratory textbook of experimental techniques for all
students of organic chemistry. It can be used in conjunction with any lab experiments to
provide the background information necessary for developing and mastering the skills
required for organic chemistry lab work. Laboratory Techniques in Organic Chemistry offers
a great deal of flexibility. It can be used in any organic laboratory with any glassware. The
basic techniques for using miniscale standard taper glassware as well as microscale 14/10
standard taper or Williamson glassware are all covered. The miniscale glassware that is
described is appropriate with virtually any 14/20 or 19/22 standard taper glassware kit.
Modern Instrumentation
Instrumental methods play a crucial role in supporting modern experiments, which provide the active learning opportunities instructors seek for their students. We feature instrumental methods that offer quick, reliable, quantitative data. NMR spectroscopy and gas
chromatography are particularly important. Our emphasis is on how to acquire good data
and how to read spectra efficiently, with real understanding. Chapters on 1H and 13C NMR,
IR, and mass spectrometry stress the practical interpretation of spectra and how they can
be used to answer questions posed in an experimental context. They describe how to deal
with real laboratory samples and include case studies of analyzed spectra.
Organization
The book is divided into six parts:
Part 1 has chapters on safety, green chemistry, and the lab notebook.
Part 2 discusses lab glassware, measurements, heating and cooling methods,
setting up organic reactions, and computational chemistry.
Part 3 introduces filtration, extraction, drying organic liquids and recovering
products, distillation, refractometry, melting points, recrystallization, and the
measurement of optical activity.
Part 4 presents the three chromatographic techniques widely used in the organic
laboratory—thin-layer, liquid, and gas chromatography.
Part 5 discusses IR, 1H and 13C NMR, MS, and UV-VIS spectra in some detail.
Part 6 introduces the design and workup of chemical reactions based on
procedures in the literature of organic chemistry.
Traditional organic qualitative analysis is available on our Web site:
www.whfreeman.com/mohrig4e.
Modern Projects and Experiments in Organic Chemistry
The accompanying laboratory manual, Modern Projects and Experiments in Organic Chemistry, comes in two complete versions:
Modern Projects and Experiments in Organic Chemistry: Miniscale and Standard Taper
Microscale (ISBN 0-7167-9779-8)
Modern Projects and Experiments in Organic Chemistry: Miniscale and Williamson
Microscale (ISBN 0-7167-3921-6)
Contents
Preface
xv
Modern Projects and Experiments is a combination of inquiry-based and traditional
experiments, plus multiweek inquiry-based projects. It is designed to provide quality
content, student accessibility, and instructor flexibility. This laboratory manual introduces
students to the way the contemporary organic lab actually functions and allows them to
experience the process of science. All of its experiments and projects are also available
through LabPartner Chemistry.
LabPartner Chemistry
W. H. Freeman’s latest offering in custom lab manuals provides instructors with a diverse
and extensive database of experiments published by W. H. Freeman and Hayden-McNeil
Publishing—all in an easy-to-use, searchable online system. With the click of a button,
instructors can choose from a variety of traditional and inquiry-based labs, including the
experiments from Modern Projects and Experiments in Organic Chemistry. LabPartner Chemistry sorts labs in a number of ways, from topic, title, and author, to page count, estimated
completion time, and prerequisite knowledge level. Add content on lab techniques and
safety, reorder the labs to fit your syllabus, and include your original experiments with
ease. Wrap it all up in an array of bindings, formats, and designs. It’s the next step in custom lab publishing. Visit http://www.whfreeman.com/labpartner to learn more.
Acknowledgments
We have benefited greatly from the insights and thoughtful critiques of the reviewers for
this edition:
Dan Blanchard, Kutztown University of Pennsylvania
Jackie Bortiatynski, Pennsylvania State University
Christine DiMeglio, Yale University
John Dolhun, Massachusetts Institute of Technology
Jane Greco, Johns Hopkins University
Rich Gurney, Simmons College
James E. Hanson, Seton Hall University
Paul R. Hanson, University of Kansas
Steven A. Kinsley, Washington University in St. Louis
Deborah Lieberman, University of Cincinnati
Joan Mutanyatta-Comar, Georgia State University
Owen P. Priest, Northwestern University
Nancy I. Totah, Syracuse University
Steven M. Wietstock, University of Notre Dame
Courtney Lyons, our editor at W. H. Freeman and Company, was great in so many
ways throughout the project, from the beginning to its final stages; her skillful editing
and thoughtful critiques have made this a better textbook and it has been a pleasure to
work with her. We especially thank Jane Wissinger of the University of Minnesota and
Steven Drew and Elisabeth Haase, our colleagues at Carleton College, who provided
helpful insights regarding specific chapters for this edition. The entire team at Freeman,
especially Georgia Lee Hadler and Julia DeRosa, have been effective in coordinating the
xvi
Contents
Preface
copyediting and publication processes. We thank Diana Blume for her creative design
elements. Finally, we express heartfelt thanks for the patience and support of our spouses,
Adrienne Mohrig, Ellie Schatz, and Bill Hammond, during the several editions of Laboratory Techniques in Organic Chemistry.
We hope that teachers and students of organic chemistry find our approach to laboratory
techniques effective, and we would be pleased to hear from those who use our book. Please
write to us in care of the Chemistry Acquisitions Editor at W. H. Freeman and Company,
41 Madison Avenue, New York, NY 10010, or e-mail us at chemistry@whfreeman.com.
PART
1
Introduction to the
Organic Laboratory
Essay—The Role of the Laboratory
Organic chemistry provides us with a framework to understand ourselves and the
world in which we live. Organic compounds are present everywhere in our lives—they
comprise the food, fabrics, cosmetics, and medications that we use on a daily basis. By
studying how the molecules of life interact with one another, we can understand the
chemical processes that sustain life and discover new compounds that could potentially
transform our lives. For example, organic chemistry was used to discover the cholesterollowering blockbuster drug, Lipitor®. Current research in organic semiconductors,
which are more flexible, cheaper, and lighter in weight than silicon-based components,
could lead to solar cells incorporated into clothing, backpacks, and virtually anything.
The purpose of this textbook is to provide you with the skills and knowledge to make
new discoveries like these, view the world from a new perspective, and ultimately harness the power of organic chemistry.
It is in the laboratory that we learn “how we know what we know.” The lab deals
with the processes of scientific inquiry that organic chemists use. Although the techniques may at first appear complicated and mysterious, they are essential tools for
addressing the central questions of this experimental science, which include:
What chemical compounds are present in this material?
What is this compound and what are its properties?
Is this compound pure?
How could I make this compound?
How does this reaction take place?
How can I separate my product from other reaction side products?
Keep in mind that the skills you will be learning are very practical and there is a
reason for each and every step. You should make it your business to understand why
these steps are necessary and how they accomplish the desired result. If you can answer
1
2
Part 1
Introduction to the Organic Laboratory
these questions for every lab session, you have fulfilled the most basic criterion for
satisfactory lab work.
You may also have opportunities to test your own ideas by designing new experiments. Whenever you venture into the unknown, it becomes even more important to be
well informed and organized before you start any experiments. Safety should be a primary
concern, so you will need to recognize potential hazards, anticipate possible outcomes,
and responsibly dispose of chemical waste. In order to make sense of your data and
report your findings to others, you will need to keep careful records of your experiments. The first section of this textbook introduces you to reliable sources of information, safety procedures, ways to protect the environment, and standards for laboratory
record-keeping. It is important to make these practices part of your normal laboratory
routine. If you are ever unsure about your preparation for lab, ask your instructor.
There is no substitute for witnessing chemical transformations and performing
separation processes in the laboratory. Lab work enlivens the chemistry that you are
learning “on paper” and helps you understand how things work. Color changes, phase
changes, and spectral data are fun to witness and fun to analyze and understand. Enjoy
this opportunity to experiment in chemistry and come to lab prepared and with your
brain engaged!
chapter
1
All of the stories
in this chapter are
based on the authors’
experiences working
and teaching in
the lab.
Safety in the Laboratory
Carrie used a graduated cylinder to measure a volume of concentrated acid
solution at her lab bench. As she prepared to record data in her notebook
later in the day, she picked up her pen from the bench-top and absentmindedly started chewing on the cap. Suddenly, she felt a burning sensation in her mouth and yelled, “It’s hot!” The lab instructor directed her
to the sink to thoroughly rinse her mouth with water and she suffered no
long-term injury.
This incident is like most laboratory accidents; it resulted from
inappropriate lab practices and inattention, and it was preventable.
Carrie should have handled the concentrated acid in a fume hood
and, with advice from her instructor, immediately cleaned up the
acid she must have spilled. She should never have introduced any
object in the lab into her mouth. With appropriate knowledge, most
accidents are easily remedied. In this case, the instructor knew from
her shout what the exposure must have been and advocated a reasonable treatment.
Accidents in teaching laboratories are extremely rare; instructors with 20 years of teaching experience may witness fewer than
five mishaps. Instructors and institutions continually implement
changes to the curriculum and laboratory environment that improve
safety. Experiments are now designed to use very small amounts
of material, which minimizes the hazards associated with chemical exposure and fire. Laboratories provide greater access to fume
hoods for performing reactions, and instructors choose the least
hazardous materials for accomplishing transformations. Nevertheless, you play an important role in ensuring that the laboratory is as
safe as possible.
You can rely on this textbook and your teacher for instruction
in safe and proper laboratory procedures. You are responsible
for developing good laboratory habits: Know and understand
the laboratory procedure and associated hazards, practice good
technique, and be aware of your actions and the actions of those
around you. Habits like these are transferable to other situations
and developing them will not only enable you to be effective in
the laboratory but also help you to become a valuable employee
and citizen.
The goal of safety training is to manage hazards in order to
minimize the risk of accidental chemical exposure, personal injury,
or damage to property or the environment.
Before you begin laboratory work, familiarize yourself with
the general laboratory safety rules (listed below) that govern
work at any institution.
At the first meeting of your lab class, learn institutional safety
policies regarding personal protective equipment (PPE), the
location and use of safety equipment, and procedures to be
followed in emergency situations.
For each individual experiment, note the safety considerations
identified in the description of the procedure, the hazards
3
4
Part 1
Introduction to the Organic Laboratory
associated with the specific chemicals you will use, and the
waste disposal instructions.
In addition to knowledge of basic laboratory safety, you need
to learn how to work safely with organic chemicals. Many organic
compounds are flammable or toxic. Many can be absorbed through
the skin; others are volatile and can be ingested by inhalation.
Become familiar with and use chemical hazard documentation,
such as the Globally Harmonized System (GHS) of hazard information and Material Safety Data Sheets (MSDSs) or Safety Data Sheets
(SDSs). Despite the hazards, organic compounds can be handled
with a minimum of risk if you are adequately informed about the
hazards and safe handling procedures, and if you use common
sense while you are in the lab.
1.1
General Safety
Rules
General Safety Information
1. Do not work alone in the laboratory. Being alone in a situation
in which accidents can occur can be life threatening.
2. Always perform an experiment as specified. Do not modify the
conditions or perform new experiments without authorization
from your instructor.
3. Wear clothing that covers and protects your body; use appropriate protective equipment, such as goggles and gloves; and
tie back long hair at all times in the laboratory. Shorts, tank
tops, bare feet, sandals, or high heels are not suitable attire for
the lab. Loose clothing and loose long hair are fire hazards or
could become entangled in an apparatus. Wear safety glasses or
chemical splash goggles at all times in the laboratory. Laboratory aprons or coats may be required by your instructor.
4. Be aware of others working near you and the hazards associated with their experiments. Often the person hurt worst in an
accident is the one standing next to the place where the accident
occurred. Communicate with others and make them aware of
the hazards associated with your work.
5. Never eat, drink, chew gum, apply makeup, or remove or
insert contact lenses in the laboratory. Never directly inhale
or taste any substance or introduce any laboratory equipment,
such as a piece of glassware or a writing utensil, into your
mouth. Wash your hands with soap and water before you leave
the laboratory to avoid accidentally contaminating the outside
environment, including items that you may place into your
mouth with your hands.
6. Notify your instructor if you have chemical sensitivities or
allergies or if you are pregnant. Discuss these conditions and
the advisability of working in the organic chemistry laboratory
with appropriate medical professionals.
7. Read and understand the hazard documentation regarding
any chemicals you plan to use in an experiment. This can be
found in Material Safety Data Sheets (MSDSs) or Safety Data
Sheets (SDSs).
Chapter 1
Safety in the Laboratory
5
8. Know where to find and how to use safety equipment, such as
the eye wash station, safety shower, fire extinguisher, fire blanket, first aid kit, telephone, and fire alarm pulls.
9. Report injuries, accidents, and other incidents to your instruc­tor
and follow his or her instructions for treatment and documentation.
10. Properly dispose of chemical waste, including chemically
contaminated disposable materials, such as syringes, pipets,
gloves, and paper. Do not dispose of any chemicals by pouring
them down the drain or putting them in the trash can without
approval from your instructor.
Chemical Hygiene
Plan
1.2
Your institution will have a chemical hygiene plan that outlines the
safety regulations and procedures that apply in your laboratory. It will
provide contact information and other information about local safety
rules and processes for managing laboratory fires, injuries, chemical
spills, and chemical waste. You can search the institutional web pages
or ask your instructor for access to the chemical hygiene plan.
Preventing Chemical Exposure
Mary was wearing nitrile gloves while performing an extraction with
dichloromethane. Although she spilled some solution on her gloves, she
continued working until she felt her hands burning. She peeled off the
gloves and washed her hands thoroughly, but a burning sensation under
her ring persisted for 5 to 10 minutes thereafter. She realized that the
dichloromethane solution easily passed through her gloves and she wondered whether her exposure to dichloromethane and the compounds dissolved in it would have an adverse effect on her health.
Personal Protective
Equipment
This example illustrates the importance of understanding the level
of protection provided by personal protective equipment (PPE) and
other safety features in the laboratory.
Never assume that clothing, gloves, lab coats, or aprons
will protect you from every kind of chemical exposure. If
chemicals are splashed onto your clothing or your gloves,
remove the articles immediately and thoroughly wash the
affected area of your body.
If you spill a chemical directly on your skin, wash the affected
area thoroughly with water for 10–15 min, and notify your
instructor.
Eye protection. Safety glasses with side shields have impactresistant lenses that protect your eyes from flying particles, but they
provide little protection from chemicals. Chemical splash goggles
fit snugly against your face and will guard against the impact from
flying objects and protect your eyes from liquid splashes, chemical
vapors, and particulate or corrosive chemicals. These are the best
choice for the organic chemistry laboratory and your instructor will
be able to recommend an appropriate style to purchase. If you wear
prescription eyeglasses, you should wear chemical splash goggles
6
Part 1
Introduction to the Organic Laboratory
over your corrective lenses. Contact lenses could be damaged from
exposure to chemicals and therefore you should not wear them in
the laboratory. Nevertheless, many organizations have removed
restrictions on wearing contact lenses in the lab because concerns
that they contribute to the likelihood or severity of eye damage
seem to be unfounded. If you choose to wear contact lenses in the
laboratory, you must also wear chemical splash goggles to protect
your eyes. Because wearing chemical splash goggles is one of the
most important steps you can take to safely work in the laboratory,
we will use a splash goggle icon (see margin figure) to identify
important safety information throughout this textbook.
Protective attire. Clothes should cover your body from your neck to
at least your knees and shoes should completely cover your feet in
the laboratory. Cotton clothing is best because synthetic fabrics could
melt in a fire or undergo a reaction that causes the fabric to adhere to
the skin and severely burn it. Wearing a lab coat or apron will help
protect your body. For footwear, leather provides better protection
than other fabrics against accidental chemical spills. Your institution
may have more stringent requirements for covering your body.
Disposable gloves. Apart from goggles, gloves are the most common form of PPE used in the organic laboratory. Because disposable
gloves are thin, many organic compounds permeate them quickly
and they provide “splash protection” only. This means that once
you spill chemicals on your gloves, you should remove them,
wash your hands thoroughly, and put on a fresh pair of gloves.
Ask your instructor how to best dispose of contaminated gloves.
Table 1.1 lists a few common chemicals and the chemical resistance to each one provided by three common types of gloves. A
T a b l e
1 . 1
 hemical resistance of common types of gloves
C
to various compounds
Glove type
Compound
Neoprene
Nitrile
Latex
Acetone
Chloroform
Dichloromethane
Diethyl ether
Ethanol
Ethyl acetate
Hexane
Hydrogen peroxide
Methanol
Nitric acid (conc.)
Sodium hydroxide
Sulfuric acid (conc.)
Toluene
Good
Good
Fair
Very good
Very good
Good
Excellent
Excellent
Very good
Good
Very good
Good
Fair
Fair
Poor
Poor
Good
Good
Poor
Excellent
Good
Fair
Poor
Good
Poor
Fair
Good
Poor
Poor
Poor
Good
Fair
Poor
Good
Fair
Poor
Excellent
Poor
Poor
The information in this table was compiled from http://www.microflex.com,
http://www.ansellpro.com, and “Chemical Resistance and Barrier Guide for Nitrile
and Natural Rubber Latex Gloves,” Safeskin Corporation, San Diego, CA, 1999.
Safety in the Laboratory
7
Gretchen Hofmeister
Chapter 1
FIGURE 1.1 A typical
chemical fume hood.
more extensive chemical resistance table for types of gloves may
be posted in your laboratory. Additional information on disposable
gloves and tables listing glove types and their chemical resistance
are also available from many websites, for example:
http://www.microflex.com
http://www.ansellpro.com
http://chemistry.umeche.maine.edu/Safety.html
Chemical Fume
Hoods
You can protect yourself from accidentally inhaling noxious chemical fumes, toxic vapors, or dust from finely powdered materials by
handling chemicals inside a fume hood. A typical fume hood with
a movable sash is depicted in Figure 1.1. The sash is constructed
of laminated safety glass and can open and close either vertically
or horizontally. When the hood is turned on, a continuous flow of
air sweeps over the bench top and removes vapors or fumes from
the area. The volume of air that flows through the sash opening is
constant, so the rate of flow, or face velocity, is greater when the
sash is closed than when it is open. Most hoods have stops or signs
indicating the maximum open sash position that is safe for handling
chemicals. If you are unsure what is a safe sash position for the
hoods in your laboratory, ask your instructor.
Because many compounds used in the organic laboratory are at
least potentially dangerous, the best practice is to run every experiment in a hood, if possible. Your instructor will tell you when an
experiment must be carried out in a hood.
Make sure that the hood is turned on before you use it.
Never position your face near the sash opening or place your
head inside a hood when chemicals are present. Keep the
sash in front of your face so that you look through the sash to
monitor what is inside the hood.
Place chemicals and equipment at least six inches behind the
sash opening.
8
Part 1
Introduction to the Organic Laboratory
Elevate reaction flasks and other equipment at least two
inches above the hood floor to ensure good airflow around the
apparatus.
When you are not actively manipulating equipment in the
hood, adjust the sash so that it covers most of the hood
opening and shields you from the materials inside.
A link to a YouTube video, created at Dartmouth College, which
describes the function and use of fume hoods, can be found at:
http://www.youtube.com/watch?v=nlAaEpWQdwA .
Chemical Hygiene
Poor housekeeping often leads to accidental chemical exposure. In
addition to your own bench area, the balance and chemical dispensing and waste areas must be kept clean and orderly.
If you spill anything while measuring out your chemicals,
notify your instructor and clean it up immediately.
After weighing a chemical, replace the cap on the container
and dispose of the weighing paper in the appropriate
receptacle.
Clean glassware, spatulas, and other equipment as soon as
possible after using them.
Always remove gloves, lab coat, or apron before leaving the
laboratory to prevent widespread chemical contamination.
Dispose of chemical waste appropriately.
1.3
Preventing Cuts and Burns
As Harvey adjusted a pipet bulb over the end of a disposable glass pipet,
the pipet broke and the broken end jammed into his thumb, cutting it badly.
Harvey required hand surgery to repair a damaged nerve and he could not
manipulate his thumb for several months afterward.
Cuts
While Harvey’s accident was unusually severe, the most common
laboratory injuries are cuts from broken glass or puncture wounds
from syringe needles. For this reason, handle glassware and sharp
objects with care.
Check the rims of beakers, flasks, and other glassware for chips
and discard any piece of glassware that is chipped.
If you break a piece of glassware, use a dustpan and broom
instead of your hands to pick up the broken pieces.
Do not put broken glass or used syringe needles in the trash
can. Dispose of them separately—broken glass in the broken
glass container and syringe needles in the sharps receptacle.
If a stopper, stopcock, or other glass item seems stuck, do not
force it. Ask your instructor, who is more experienced with the
equipment, for assistance in these cases.
To safely insert thermometers or glass tubes into corks, rubber
stoppers, and thermometer adapters, lubricate the end of the
glass with a drop of water or glycerol, hold the tube near the
lubricated end, and insert it slowly by gently rotating it.
Chapter 1
Safety in the Laboratory
9
Never push on the end of a glass tube or a thermometer to
insert it into a stopper; it may break and the shattered end
could be driven into your hand.
Remember that glass and the tops of hot plates look the same when
they are hot as when they are cold. Steam and hot liquids also cause
severe burns. Liquid nitrogen and dry ice can quickly give you
frostbite.
Burns
Do not put hot glass on a bench where someone else might
pick it up.
Turn off the steam source before removing containers from the
top of a steam bath.
The screws or valve stems attached to the rounded handle that
controls a steam line can become very hot; be careful not to
touch them when you turn the steam on or off.
Move containers of hot liquids only if necessary and use a
clamp, tongs, rubber mitts, or oven gloves to hold them.
Wear insulated gloves when handling dry ice and wear
insulated gloves, a face shield, long pants, and long sleeves
when dispensing liquid nitrogen.
1.4
Preventing Fires and Explosions
Michael was purifying a reaction product by distillation on the laboratory bench. The product mixture also contained diethyl ether. About halfway through the distillation, the distilled material caught fire. Michael’s
instructor used a fire extinguisher to put out the fire and assisted Michael
in turning off the heating mantle and lifting the distillation system away
from the heat source. As soon as possible, the entire apparatus was relocated
to the fume hood and Michael was instructed to chill the receiving flask in
an ice bath, to minimize the escape of flammable vapors from the flask.
Fires
Hydrocarbons and many of their derivatives are flammable and the
potential for fire in the organic laboratory always exists. Fortunately,
most modern lab procedures require only small amounts of material, minimizing the risk of fire. Flammable compounds do not spontaneously combust in air; they require a spark, a flame, or heat to
catalyze the reaction. Vapors from low-boiling organic liquids, such
as diethyl ether or pentane, can travel over long distances at bench
or floor level (they are heavier than air) and thus they are susceptible
to ignition by a source that is located up to 10 ft away. The best way
to prevent a fire is to prevent ignition.
Four sources of ignition are present in the organic laboratory:
open flames, hot surfaces such as hot plates or heating mantles
(Figure 1.2), faulty electrical equipment, and chemicals. Flames,
such as those produced by Bunsen burners, should be used rarely in
the organic laboratory and only with the permission of your instructor. Hot plates and heating mantles, however, are used routinely.
The thermostat on most hot plates is not sealed and can spark when
it cycles on and off. The spark can ignite flammable vapors from
10
Part 1
Introduction to the Organic Laboratory
AT
T
EA
H
R
STI
FIGURE 1.2 Heating
devices.
Ceramic heating mantle
HE
R
STI
Hot plate/stirrer
an open container such as a beaker. An organic solvent spilled or
heated recklessly on a hot plate surface can also burst into flames.
Chemical reactions sometimes produce enough heat to cause a fire
and explosion. For example, in the reaction of metallic sodium with
water, the hydrogen gas that forms in the reaction can explode and
ignite a volatile solvent that happens to be nearby.
Never bring a lighted Bunsen burner or match near a lowboiling-point flammable liquid.
Work in a fume hood, where flammable vapors are swept
away from sources of ignition before they can catch fire.
Flammable solvents with boiling points below 100°C—such as
diethyl ether, methanol, pentane, hexane, and acetone—should
be distilled, heated, or evaporated on a steam bath or heating
mantle, never on a hot plate or with a Bunsen burner.
Use an Erlenmeyer flask fitted with a stopper—never an open
beaker—for temporarily storing flammable solvents at your
work area.
Before pouring a volatile organic liquid, remove any hot
heating mantle or hot plate from the vicinity.
Do not use appliances with frayed or damaged electrical cords;
notify your instructor of faulty equipment so it can be removed
and replaced.
Explosions
Explosive compounds combine a fuel and an oxidant in the same
molecule and decompose to evolve gaseous products with enough
energy for the hot, expanding gases to produce a shock wave. Ammonium nitrate, NH41NO32, explosively produces gaseous N2O and
H2O when detonated. You will not handle explosive chemicals in the
instructional laboratory, although some chemical reactions, when
improperly performed, can rapidly generate hot gases and cause an
explosion.
A more likely scenario that you could encounter is an explosion
due to accidentally allowing pressure to build up inside a closed
vessel. If the pressure gets high enough or if there is a weakness in
the wall of the vessel, it can fail in an explosive manner.
Chapter 1
Safety in the Laboratory
Star crack
FIGURE 1.3 Roundbottomed flask with a
star crack.
11
Unless your instructor specifies otherwise, never heat a
closed system! Some glassware, however, is designed to
sustain pressure when heated and it may be used in certain
applications.
Never completely close off an apparatus in which a gas is
being evolved: always provide a vent in order to prevent an
explosion.
Routinely check flasks for defects, such as star cracks (Figure 1.3),
which may lead to a catastrophic failure of the flask.
Perform reactions in a hood and use the sash to cover the
opening when you are not actively manipulating equipment.
The hood sash is constructed of laminated safety glass, which
is a blast shield.
Implosions are the opposite of explosions. They occur when containers under vacuum cannot sustain the pressure exerted by the
outside atmosphere and fail catastrophically. You will be handling
evacuated flasks in the laboratory if you perform vacuum filtrations
(Section 9.4), rotary evaporations (Section 11.4), or vacuum distillations (Section 12.7). Vacuum flasks are also used for holding very
cold liquids (Section 6.4). Filter flasks and glassware used for rotary
evaporation are heavy walled and designed to sustain pressure;
therefore, the danger of implosion is small.
In order to prevent injuries from accidental implosions:
Implosions
Routinely check flasks for defects, such as star cracks (Figure 1.3),
which may lead to a catastrophic failure of the flask.
Perform vacuum-based procedures in a hood (with the hood
sash serving as protection) or behind a safety shield, which is
a heavy, portable buffer constructed of high-impact-resistant
polycarbonate.
Wrap containers that are routinely kept under vacuum with
plastic mesh or electrical tape. Examples are filter flasks and
Dewar flasks, which are vacuum-sealed thermos flasks for
holding very cold liquids. Never use a Dewar flask that does
not have a protective metal case on the outside. If a flask
should implode, the metal case or tape or mesh will contain
the broken glass and prevent flying shards from causing
injury.
1.5
What to Do if an Accident Occurs
Always inform your instructor immediately of any safety incident
or accident that happens to you or your neighbors. If a physician’s
attention is necessary, an injured person should always be accompanied to the medical facility; the injury may be more serious than it
initially appears.
Fire
Colleges and universities all have standard policies regarding the
handling of fires, which will be described in the Chemical Hygiene
Plan and by your instructor. Learn where the exits from your
12
Part 1
Introduction to the Organic Laboratory
laboratory are located. In case of a fire in the lab, get out of danger
and notify your instructor as soon as possible.
Fire extinguishers. There are several types of fire extinguishers, and
your instructor may demonstrate their use. Your lab is probably
equipped with either class BC or class ABC dry chemical fire extinguishers suitable for solvent or electrical fires. At some institutions,
instructors are the only people who are allowed to handle fire extinguishers in the laboratory.
To use a fire extinguisher, aim low and direct the nozzle first
toward the edge of the fire and then toward the middle.
Do not use water to extinguish chemical fires.
Fire blankets. Fire blankets are used to smother a fire involving a
person’s clothing. Know where the fire blanket is located in your lab.
If a person’s clothing catches fire, ease the person to the floor
and roll the person’s body tightly in a fire blanket. When the
blanket is wrapped around a person who is standing, it may
direct the flames toward the person’s face.
If your clothing is on fire, do not run.
Safety shower. The typical safety shower dumps a huge volume of
water in a short period of time and is effective when a person’s clothing or hair is ablaze and speed is of the essence. Do not use the safety
shower routinely, but do not hesitate to use it in an emergency.
Chemical Burns
The first thing to do if any chemical is spilled on your skin, unless
you have been specifically told otherwise, is to wash the area well
with water for 10–15 min. This will rinse away the excess chemical
reagent. For acids, bases, and toxic chemicals, thorough washing
with water will lessen pain later. Skin contact with a strong base usually does not produce immediate pain or irritation, but serious tissue
damage (especially to the eyes) can occur if the affected area is not
immediately washed with copious amounts of water. Notify your
instructor immediately if any chemical is spilled on your skin.
Seek immediate medical treatment for any serious chemical burn.
Safety shower. Safety showers are effective for acid burns and other
spills of corrosive, irritating, or toxic chemicals on the skin or clothing. Remove clothing that has been contaminated by chemicals. Do
this as quickly as possible while in the shower.
Eye wash station. Learn the location of the eye wash stations in your
laboratory and examine the instructions on them during the first
(check-in) lab session. If you accidentally splash something in your
eyes, immediately use the eye wash station to rinse them with copious quantities of slightly warm water for 10–15 min.
Do not use very cold water because it can damage the eyeballs.
Position your head so that the stream of water from the eye
wash fountain is directed at your eyes.
Chapter 1
Safety in the Laboratory
13
Hold your eyes open to allow the water to flush the eyeballs
for 10–15 min. Because this position can be difficult to maintain,
assistance may be required. Do not hesitate to call for help.
Move eyeballs up, down, and sideways while flushing with
water to wash behind the eyelids.
If you are wearing contact lenses, they must be removed for
the use of an eye wash station to be effective, an operation that
is extremely difficult if a chemical is causing severe discomfort
to your eyes. Therefore, it is prudent not to wear contact
lenses in the laboratory.
Seek medical treatment immediately after using the eye wash
for any chemical splash in the eyes.
Learn the location of the first aid kit and the materials it contains
for the treatment of simple cuts and burns. All injuries, no matter
how slight, should be reported to your instructor immediately. Seek
immediate medical attention for anything except the most trivial cut
or burn.
Minor Cuts and
Burns
First aid kit. Your laboratory or a nearby stockroom may contain
a basic first aid kit consisting of such items as adhesive bandages,
sterile pads, and adhesive tape for treating a small cut or burn.
Apply pressure to cuts to help slow the bleeding. Apply a
bandage when the bleeding has stopped. If the cut is large or
deep, seek immediate medical attention.
When the cut is a result of broken glass, ensure that there is no
glass remaining in the wound; if you are unsure, seek medical
attention.
For a heat burn, apply cold water for 10–15 min. Seek
immediate medical attention for any extensive burn.
For a cold burn, do not apply heat. Instead, treat the affected area
with large volumes of tepid water and seek medical attention.
1.6
Chemical Toxicology
Most substances are toxic at some level, but the level varies over a
wide range. A major concern in chemical toxicology is quantity or
dosage. It is important that you understand how toxic compounds
can be handled safely in the organic laboratory.
The toxicity of a compound refers to its ability to produce injury
once it reaches a susceptible site in the body. A compound’s toxicity is related to its probability of causing injury and is a speciesdependent term. What is toxic for people may not be toxic for other
animals and vice versa. A substance is acutely toxic if it causes a
toxic effect in a short time; it is chronically toxic if it causes toxic
effects with repeated exposures over a long time.
Fortunately, not all toxic substances that accidentally enter the
body reach a site where they can be harmful. Even if a toxic substance is absorbed, it is often excreted rapidly. Our body protects
us with various devices: the nose, scavenger cells, metabolism, and
14
Part 1
Introduction to the Organic Laboratory
rapid exchange of good air for bad. Many foreign substances are
detoxified and discharged from the body very quickly.
Action of Toxic
Substances on the
Body
Although many substances are toxic to the entire system (arsenic, for
example), many others are site specific. Carbon monoxide, for example, forms a complex with the hemoglobin in our blood, diminishing
the blood’s ability to absorb and release oxygen; it also poisons the
action of mitochondrial aerobic metabolism.
In some cases, the metabolites of a compound are more toxic
than the original compound. An example is methanol poisoning.
The formic acid that is formed by the body’s metabolism of methanol affects the optic nerve, causing blindness. The metabolism of
some relatively harmless polycyclic aromatic hydrocarbons produces potent carcinogenic compounds. As far as our health is concerned, it does not matter whether the toxicity is due to the original
substance or a metabolic product of it.
Toxicity Testing and
Reporting
Consumers are protected by a series of laws that define toxicity, the
legal limits and dosages of toxic materials, and the procedures for
measuring toxicities.
Acute oral toxicity is measured in terms of LD50. (LD stands for
lethal dose.) LD50 represents the dose, in milligrams per kilogram
of body weight, that will be fatal to 50% of a certain population of
animals. Other tests include dermal toxicity (skin sensitization) and
inhalation toxicity. In the case of inhalation, LC50 (LC stands for
lethal concentration) is used to standardize toxic properties. Toxicity
information is included as part of the MSDS or SDS for chemicals
that are commercially available. A wall chart of toxicities for many
common organic compounds may be hanging in your laboratory or
near your stockroom.
1.7
Identifying Chemicals and Understanding
Chemical Hazards
A set of laboratory manual instructions read: “If a yellow/orange color persists in your reaction mixture, add NaHSO3(aq) (sodium bisulfite solution)
gradually by pipetfuls (with swirling to mix) until the color fades.” Jody
started this process and became concerned when the color did not disappear
after adding five pipetfuls of solution. She approached the instructor, who
asked to see the container of the solution she was using. This led to the discovery that Jody was, in fact, adding sodium bicarbonate (NaHCO3(aq)) to
the reaction mixture; she had read the label on the bottle as “sodium bi…”
and assumed it was what she needed. Instead of adding a reducing agent,
Jody was adding a base!
Although this laboratory mishap did not lead to an accident, it
demonstrates a common and potentially dangerous oversight in the
organic chemistry lab. Fortunately, Jody knew that something was
wrong when she did not witness the expected color change. Safety
in the laboratory critically depends on your knowledge of chemical
names and structures, your understanding of chemical reactivity
and potential hazards, the proper labeling of chemicals, and your
careful attention.
Chapter 1
Safety in the Laboratory
Identifying the
Chemical
15
Chemists have invested a great deal of energy in devising systematic
names of chemicals for good reason, and you should never consider nomenclature to be “unimportant.” The IUPAC (International
Union of Pure and Applied Chemistry) naming system is fairly complex, however, and people are bound to make mistakes. In addition
to IUPAC names, common names are still in regular use, and it can
be confusing to work with compounds that are identified by multiple names. The American Chemical Society’s Chemical Abstracts
Service (CAS) has developed an identification system in which
each chemical is given a unique number. By correlating the CAS
number with structure, you can avoid the confusion associated with
multiple names.
Commercial suppliers of chemicals, such as Sigma-Aldrich and
Acros Organics, have electronic searchable databases of the names,
structures, CAS numbers, properties, and hazard information associated with every chemical that they sell. Those databases are among
the most convenient places to go for information:
http://www.sigmaaldrich.com
http://www.acros.com
A screenshot from a search for “acetyl chloride” on the SigmaAldrich website shows that, in addition to the name and structure,
the CAS number, molecular weight, boiling point, and density are
provided. These have been highlighted in blue boxes in Figure 1.4.
Download MSDS via this link
Sigma-Aldrich
This tab will provide hazard information
FIGURE 1.4 Screenshot from a Sigma-Aldrich search for the compound acetyl chloride,
with some information highlighted in blue boxes. Screenshot captured from http://www.
sigmaaldrich.com.
16
Part 1
Global Harmonized
System of Safety
Information
Introduction to the Organic Laboratory
A Global Harmonized System (GHS) of classifying and labeling
chemicals has been developed by the United Nations for identifying the hazards associated with all chemicals that are manufactured
and shipped around the world, often in large quantities. The United
States Department of Labor Occupational Safety and Health Administration (OSHA) has revised its Hazard Communication Standard
to align with the GHS. The GHS is the primary information system
described in this textbook. GHS information is conveyed on chemical labels and chemical suppliers’ websites, as shown in Figure 1.5,
which is a screenshot from a search for acetyl chloride on the Acros
website.
The safety information regarding acetyl chloride is shown in
the third section of the screenshot, and the top half of this section
provides GHS information:
GHS pictograms are described in Figure 1.6, and some
definitions of the hazard terms are provided in Table 1.2. Some
hazards are represented by two different pictograms in Figure
1.6: Self-Reactives and Organic Peroxides are depicted by
either the Flame or the Exploding Bomb, and Acute Toxicity
is depicted by either the Exclamation Mark or the Skull and
Crossbones. In these cases, the severity of the hazard dictates
which pictogram is used. Greater hazards are labeled with
the more serious pictogram (Exploding Bomb or Skull and
Download MSDS via this link
FIGURE 1.5 Screenshot from an Acros Organics search for the compound acetyl chloride,
with GHS information and MSDS link highlighted in blue. Screenshot captured from http://
www.acros.com.
Acros
GHS Information
Chapter 1
Safety in the Laboratory
17
Crossbones) and lesser hazards are labeled with the less
serious pictogram (Flame or Exclamation Mark).
Two signal words are used: “Warning” is less severe; “Danger”
is more severe and is associated with the increased hazard
categories 1 or 2. In the GHS system, smaller numbers indicate
a greater hazard than bigger numbers.
H (hazard) statements provide more specific information about
the hazard.
P (precautionary) statements explain how to minimize risks
associated with handling the chemical and what to do in case
of accidental exposure to the chemical.
The letter/number codes in front of the Hazard and Precautionary
statements are for reference purposes. The Hazard, Risk, and Safety
T a b l e
1 . 2
Definitions associated with chemical hazards
Term
Definition
Allergen
Aspiration
A chemical that causes an adverse immune response.
The entry of a liquid or solid chemical into the trachea and lower respiratory
system through the oral or nasal cavity or from vomiting.
A chemical that causes cancer or increases its incidence in humans or animals.
A chemical that causes destruction of living tissue at the site of contact.
A chemical or mixture of chemicals that produces a damaging release of energy
and gas when detonated by ignition, shock, or high temperature.
A chemical that is easily ignited and burns rapidly. (Inflammable is a synonym;
it means the same thing.)
A chemical that causes reversible damage, such as redness, swelling, itching, or
a rash at the site of contact.
A chemical that causes tears.
The concentration of a chemical in air or water that causes the death of 50%
(one half) of a group of test animals.
The amount of a chemical, given all at once, that causes the death of 50% (one
half) of a group of test animals.
A chemical that increases the occurrence of mutations in populations of cells or
organisms.
A chemical with structure R!O!O!R, which can explode upon concentration
or sudden shock.
A chemical that can rapidly bring about an oxidation reaction by supplying
oxygen or receiving electrons.
An extremely toxic chemical.
A chemical that, within 5 min, spontaneously catches fire in air.
A thermally unstable chemical that is liable to decompose in a strongly
exothermic fashion in the absence of air. (In the GHS this excludes explosives,
organic peroxides, and oxidizers.)
A chemical that causes an adverse immune reaction upon repeated exposure.
A chemical that causes physical defects in a developing fetus.
A chemical that causes adverse health effects in humans or animals.
Carcinogen
Corrosive
Explosive
Flammable
Irritant
Lachrymator
LC50
LD50
Mutagen
Organic peroxide
Oxidizer
Poison
Pyrophoric
Self-reactive
Sensitizer
Teratogen
Toxic
The definitions in this table were compiled from Hill, Jr., R. H.; Finster, D. C. Laboratory Safety for Chemistry
Students; Wiley: Hoboken, NJ, 2010; and Globally Harmonized System of Classification and Labelling of
Chemicals (GHS), 4th ed., United Nations: New York and Geneva, 2011.
18
Introduction to the Organic Laboratory
Occupational Safety and Health Administration (OSHA)
Part 1
FIGURE 1.6 Globally Harmonized System (GHS) pictograms indicating chemical hazards.
The diamond surrounding a pictogram is normally shown in red.
entries in the bottom half of the safety section in Figure 1.5 are from
the European system of coding hazards, which are self-explanatory
based on analogy to the GHS.
Figure 1.5 shows that acetyl chloride has the GHS “Danger”
signal word and the Corrosion and Flame pictograms, which are
explained in more detail in the GHS Hazard and Precautionary
Statements underneath the signal word. Based on this information,
you know to handle acetyl chloride with special care, to avoid skin
and eye contact, and to avoid using it near ignition sources. The
simplest ways to achieve this are to work with acetyl chloride in a
fume hood and to wear personal protection equipment for your eyes
and hands. In addition, “reacts violently with water” is noted as a
hazard. This indicates that you should avoid exposing this chemical to water and minimize its contact with water vapor present in
the air. If you plan to work with acetyl chloride, ask your instructor
what additional measures should be taken to prevent it from coming
into contact with water.
The Four-Diamond
Hazard Label
You may also encounter the color-coded four-diamond symbol,
developed by the National Fire Protection Association (NFPA,
Figure 1.7), on chemical labels. The four diamonds provide information on the hazards associated with handling specific compounds.
fire hazard (top, red diamond)
reactivity hazard (right, yellow diamond)
Chapter 1
19
Safety in the Laboratory
FIGURE 1.7 Fourdiamond label for
chemical containers
indicating health, fire,
reactivity, and specific
hazards. The symbol in
the specific hazard
diamond indicates that
the compound is
reactive with water and
should not come into
contact with it.
Fire hazard (red)
Health hazard
(blue)
4
1
2
Reactivity hazard
(yellow)
W
Specific hazard
(white)
specific hazard (bottom, white diamond)
health hazard (left, blue diamond)
The numbers inside the diamonds indicate the level of hazard, with
1 being the least hazardous and 4 the most hazardous. Because this
numbering system is opposite to the GHS, in which 1 indicates the
greatest hazard, it can be confusing to work with the two systems.
You should focus on learning and working with the GHS because it
will eventually supplant the NFPA labeling system.
Safety Data Sheets
Currently, all laboratories must make available a Material Safety
Data Sheet (MSDS) for every chemical used in the laboratory;
under new OSHA regulations, these will be replaced by Safety
Data Sheets (SDSs). Every MSDS or SDS contains information on
a list of topics required by law that describe the physical properties, hazards, safe handling and storage practices, and first aid
information for a chemical. Manufacturers are required to prepare
an MSDS or SDS for every chemical sold; the content is the same
for a specific chemical, but the MSDS presentation format differs
from one company to another. An MSDS from one company may
be easy to read while that from another may be more difficult to
understand. For this reason, a standardized format with 16 different sections has been prescribed for SDSs. You can access the
MSDS (or SDS, as it is phased in) for every chemical you plan to
work with in the laboratory from manufacturer’s websites or from
your institution. For example, the links to the MSDS for acetyl
chloride from Sigma-Aldrich and Acros Organics are indicated in
Figures 1.4 and 1.5.
The following websites have downloadable PDF files of MSDSs.
The first requires you to register (for free) and the latter two require
institutional subscriptions.
http://www.msds.com
http://www.MSDSonline.com
http://www.chemwatch.na.com
In addition to a complete MSDS, Chemwatch also provides mini
MSDSs that briefly summarize the essential safety information for
compounds in clear, concise language and pictograms.
20
Part 1
1.8
Introduction to the Organic Laboratory
Handling Laboratory Waste
Organic chemistry lab students were performing classification tests for
unknown compounds, which required using small amounts of a variety of
chemicals, dispensed with disposable pipets. As the lab period progressed,
the odor of organic chemicals in the lab escalated to the point of being
obnoxious. The source of odor was traced to a container for broken glass,
where used disposable pipets that were contaminated with chemicals had
been improperly discarded.
Any person using chemicals in a laboratory has a legal and
ethical responsibility to handle them properly from the moment of
purchase, during storage and use, and through appropriate disposal
procedures. The common term for this mandate is “cradle to grave”
responsibility. In the example above, the chemical residue in the
pipets should have been removed and collected in an appropriate
waste container before the pipets were discarded into the broken
glass container.
At the end of every experiment, you may have a number of reaction by-products, such as aqueous solutions from extractions, filter
paper and used drying agent coated with organic liquids, the filtrate
from a reaction mixture or a recrystallization, and possibly a metal
catalyst or other materials that need proper disposal. It is your legal
obligation, as well as that of your instructor, the stockroom personnel, and your institution, to collect and handle all laboratory wastes
in a manner consistent with federal and state requirements. Waste
that cannot be reused or reclaimed must be disposed of by incineration or burial in a landfill. The method of disposal, which depends
on local regulations and conditions, affects how waste is segregated
and collected.
Satellite
Accumulation Area
The waste containers in your lab will be located in a satellite accumulation area, which is a space for temporarily storing waste near
where it is generated. Your instructor or laboratory personnel will
assume responsibility for providing you with disposal instructions
and for properly labeling and handling the waste. It is your responsibility to check carefully—and then double-check—the label on
a waste container BEFORE you place any waste in it. If you are
in doubt about what to do with something remaining from your
experiment, consult your instructor. Placing waste in the wrong
container may cause accidental emission of a toxic substance into
the environment or may create an unsafe situation for workers managing the waste.
An organic laboratory will have several hazardous waste containers, labeled according to local regulations and protocols. In
general, glass or polyethylene containers with tight-fitting caps are
used for collecting chemical waste. These waste containers should
be kept closed when not in use. Here are some ways that waste may
be segregated in your laboratory:
Halogenated waste is organic waste containing fluorine, chlorine,
bromine, or iodine. It may be separated from other organic waste
if incineration is an option for waste disposal; incineration of
halogenated waste produces toxic HCl, for example.
Chapter 1
Safety in the Laboratory
21
Organic waste is collected in flammable waste if it is not
halogenated or nonaqueous (without water) organic waste
containers.
Aqueous (water) waste is collected separately from organic
waste because it can react violently with some organic
reagents and because it is treated differently upon storage and
disposal. Often, aqueous waste is contaminated with organic
compounds, which may be collected in an aqueous (or watercontaining) organic waste container. Depending on local
regulations, you may need to adjust the pH of aqueous waste.
Solid waste consists of spent drying agents, filter paper coated
with solvents, filter paper used in recrystallizations, and solid
material remaining after a reaction.
Toxic metal waste is waste containing heavy metals, such as
chromium and mercury.
Sink or Trash
Disposal
Except for a few materials that your instructor specifically deems
to be harmless and acceptable under local regulations, you should
NEVER dispose of any chemical or chemical-contaminated material
in the sink or in a trash can.
Further Reading
Alaimo, R. J. (Ed.) Handbook of Chemical Health and
Safety; American Chemical Society: Washington, D. C., and Oxford University Press: New
York, 2001.
American Chemical Society. Less Is Better: Guide
to Minimizing Waste in Laboratories; American
Chemical Society: Washington, DC, 2002.
Accessed electronically via http://www.acs.org
American Chemical Society. Safety in Academic
Chemistry Laboratories, 7th ed.; American Chemical Society: Washington, DC, 2003. Accessed
electronically via: http://www.acs.org
Armour, M. A. Hazardous Laboratory Chemicals
Disposal Guide, 3rd ed.; CRC Press: Boca
Raton, FL, 2003.
Furr, A. K. (Ed.) CRC Handbook of Laboratory Safety,
5th ed.; CRC Press: Boca Raton, FL, 2000.
Globally Harmonized System of Classification and
Labelling of Chemicals (GHS), 4th ed., United
Nations: New York and Geneva, 2011. Accessed
electronically via: http://www.unece.org/
Hill, Jr., R. H.; Finster, D. C. Laboratory Safety for
Chemistry Students; Wiley: Hoboken, NJ, 2010.
Lewis, Sr., R. J. Rapid Guide to Hazardous Chem­
icals in the Workplace, 4th ed.; Wiley: New York,
2000.
Lewis, Sr., R. J.; Sax, N. I. Sax’s Dangerous Properties of Industrial Materials, 12th ed.; Wiley:
Hoboken, NJ, 2012.
National Research Council of the National Academies. Prudent Practices in the Laboratory: Handling
and Management of Chemical Hazards; National
Academies Press: Washington, DC, 2011.
O’Neill, M. J. (Ed.) The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals, 15th
ed.; Royal Society of Chemistry Publishing:
Cambridge, UK, 2013.
School Chemistry Laboratory Safety Guide, U.S. Consumer Product Safety Commission and National
Institute for Occupational Safety and Health:
Bethesda, Maryland, 2006. Accessed electronically via: http://www.cpsc.gov or http://www
.cdc.gov/niosh/
United States Department of Labor Occupational Safety and Health Administration Hazard
Communication: https://www.osha.gov/dsg
/hazcom/index.html
Questions
1. Name five important safety features that
are found in your laboratory.
2. Locate the first aid kit in or near your
laboratory. Based on your institution’s
Chemical Hygiene Plan, what is the procedure that should be followed if someone in the laboratory gets a minor cut to
the skin?
22
Part 1
3. A procedure calls for you to dissolve a compound in hot ethanol. Using one of the suggested online sources (such as the SigmaAldrich or Acros Organics websites), look
up the boiling point and flammability of
ethanol. What is the best method for heating ethanol?
4. Look up the list of Chemical Waste Policies in the Chemical Hygiene Plan at your
institution. What is the policy for discarding broken glass?
5. Identify the type(s) of disposable gloves
available in your organic chemistry lab.
Would they provide good or excellent
protection from the following chemicals:
dichloromethane, ethyl ether, ethylene
glycol, and hydrogen peroxide? (You
may have to search the suggested websites, such as http://www.microflex.com,
in order to fully answer this question.)
For those chemicals against which your
gloves do not provide good protection,
what would you do if you spilled a small
amount on your glove?
6. Suppose you plan to synthesize aspirin
(acetylsalicylic acid) by reacting salicylic
acid with acetic anhydride, using 85%
phosphoric acid as a catalyst. In addition
to the main product aspirin, acetic acid
will be a side-product. Using one of the
suggested online sources (such as the
Sigma-Aldrich or Acros Organics websites), identify the CAS numbers for all of
the reagents and products (five total) in
this reaction.
7. (a) For which of the following compounds
is it hazardous to breathe dust/vapor
/fumes: acetylsalicylic acid, salicylic
acid, acetic anhydride, acetic acid,
phosphoric acid? (Use one of the suggested online sources, such as the Sigma-Aldrich or Acros Organics websites, or sources of MSDSs, to answer
this question.)
(b) Based on the boiling point or melting
point of the compounds, which are
you most likely to inhale accidentally?
(c) Based on GHS hazard information,
which would be most dangerous to
inhale?
(d) Of all these chemicals, which is most
important to handle in a fume hood?
Introduction to the Organic Laboratory
O
O
OH
OH
O
O
+
H3C
O
H3PO4
OH
CH3
O
O
Salicylic acid
Acetic anhydride
O
+
H3C
OH
CH3
Acetylsalicylic acid
Acetic acid
c h apt e r
2
Green Chemistry
You touch polycarbonate plastic every day; it is found in drinking bottles,
food containers, eyeglass lenses, CDs and DVDs, and a variety of building
materials. As with most plastics, the raw materials incorporated into traditional polycarbonates come from oil. Geoffrey Coates and his coworkers at
Cornell University have recently developed a new family of catalysts that
can effectively and economically use carbon dioxide (CO2) in polycarbonate synthesis. This technology is being commercialized to prepare resins
Chapter 2
23
Green Chemistry
for lining food and drink containers in order to replace resins derived from
bisphenol A (BPA, a suspected endocrine disruptor). Fifty percent of the
new resin (by weight) will be derived from sequestered CO2 and it will
require 50% less petroleum to produce than its traditional counterpart. If
fully utilized, this technology could eliminate 180 million metric tons of
CO2 emissions annually.
We are currently dependent on the petroleum industry for
energy and raw materials to produce consumer goods. The carbon
atoms that are incorporated into most fabrics, carpets, paints, disposable diapers, cleaning products, plastics, cosmetics, and medications come from oil, which continues to be one of our cheapest
sources of raw material. Yet oil is not a renewable resource and
its consumption contributes to climate change. Green chemistry
is sustainable chemistry; its goal is to develop chemical processes
that are safe, efficient, economical, and renewable. In 1998, Paul
Anastas and John Warner articulated the principles that now
govern the implementation of greener chemical practices in
industry, government, and education. Although we cannot immediately replace all petroleum feedstocks with renewable ones,
implementing green chemistry principles, as Coates and his colleagues have done, can make more efficient use of oil and reduce
our dependence on it.
2.1
The Principles of Green Chemistry
Green chemistry has changed chemists’ perspectives by requiring
them to think beyond creating an innovative product and to evaluate the entire lifespan of the product, from “cradle to grave.” It
leads them to ask questions about the raw materials used to make
a product, the process for making it, and its ultimate fate after use:
How safe is the product for human health and the environment?
What happens to the product once it is used or discarded?
How safe and efficient is the process of making it?
How much energy is consumed in the process of making it?
How hazardous or renewable are the raw materials?
How much waste is generated and how hazardous is it?
Chemists answer these questions for a proposed process in order to
compare it to a competing process. They then evaluate the different
strengths and weaknesses of both processes using the Twelve
Principles of Green Chemistry (Table 2.1). A 100% green process is
ideal, but it is almost impossible to accomplish all twelve principles
in any one product or process. This analysis, however, provides
a framework with which to prioritize different advantages and
approach this ideal.
The challenge of identifying and developing viable renewable
processes affects the goods we consume and the environment in
which we live. By learning ways to meet this challenge, you will
be better informed to make decisions about the work you do as a
student, consumer, and future employee. The following sections
should give you a sense that progress has been made in “greening”
24
T A B L E
Part 1
2 . 1
Introduction to the Organic Laboratory
The twelve principles of green chemistry
1. Prevention: avoid generating waste
2. Atom Economy: incorporate most atoms from the reagents into the product
3. Less Hazardous Chemical Syntheses: use and generate the least toxic materials
4. Designing Safer Chemicals: ensure that final products are nontoxic
5. Safer Solvents and Auxiliaries: use minimal and innocuous supporting materials
6. Design for Energy Efficiency: minimize energy requirements
7. Use of Renewable Feedstocks: whenever possible, use renewable raw materials
8. Reduce Derivatives: avoid introducing atoms that have to be removed later
9. Catalysis: use catalysts for efficient and less wasteful processes and re-use them when possible
10. Design for Degradation: plan for products to break down naturally into benign substances
11. Real-Time Analysis for Pollution Prevention: monitor the process to avoid accidental exposure to
hazards
12. Inherently Safer Chemistry for Accident Reduction: avoid using chemicals that are highly reactive
The information in this table was compiled from http://www.epa.gov/sciencematters/june2011/principles.htm.
the chemistry performed in industrial and educational settings and
will provide you with ideas and strategies of your own.
2.2
Green Principles Applied to Industrial Processes
The following examples are organized according to how they
address the Twelve Principles of Green Chemistry. You will notice
that although they do not meet all the criteria for a sustainable
process, they represent real progress toward that goal.
Safer Solvents
One of the simplest ways to improve a process is to replace a
hazardous solvent with a safer or more environmentally benign
alternative. An example is the process of decaffeinating coffee. Caffeine has been extracted from green coffee beans using
dichloromethane, which is a suspected carcinogen, or ethyl acetate,
which is flammable but much safer for human health and the environment. Greener methods instead employ supercritical CO2 or
water for the extraction.
Supercritical CO2. Carbon dioxide is a gas under normal conditions,
but when it is subjected to conditions of temperature and pressure
that exceed its critical point, 31.1°C and 73 atm pressure, it becomes
a single fluid-like phase, called a supercritical fluid. Supercritical
CO2 is a very good solvent with properties similar to many common
organic solvents. In addition to decaffeinating coffee, supercritical
CO2 can replace traditional and hazardous solvents in dry-cleaning
clothing, cleaning electronic and industrial parts, and chemical
reactions. At the end of these processes, the pressure is released and
the escaping CO2 gas can be easily recovered and recycled.
Water. In the quest for solvents that minimize health hazards and
risks to the environment, water would appear to be ideal because
Chapter 2
25
Green Chemistry
it is readily available and nonhazardous. But a requirement for
most reaction solvents is that they dissolve the reagents used in
the reaction, and organic compounds are largely insoluble or only
slightly soluble in water. Reactions in aqueous solution can be
promoted with water-insoluble organic compounds, however, by
using vigorous stirring, phase-transfer catalysts, or superheating by
microwaves in sealed vessels (see Section 6.3).
Organic solvents. Some necessary reactions and separation processes require organic solvents; in these cases, the safest and
environmentally most benign solvent that can accomplish the
desired goal is the best choice. The American Chemical Society
Green Chemistry Institute® (ACS GCI) has convened a body of
representatives from pharmaceutical companies, called the Pharmaceutical Roundtable, to guide the chemical community in choosing
greener organic solvents. This group has evaluated solvents in five
categories—safety, health, environment (air), environment (water),
and environment (waste)—and scored them from 1 (most benign)
to 10 (least favorable) in each category. The scores for a selection
of organic solvents, along with their boiling points and water
solubilities, are listed in Table 2.2. These data indicate that solvents
such as hexane, benzene, chloroform, dichloromethane, and ethyl
ether should be avoided and replaced with lower-scoring alternatives where possible.
Catalysts are extremely important because they can make reactions
more efficient and effective. They “activate” reagents by interacting
Catalysis
T able
2 . 2
ACS GCI Pharmaceutical Roundtable Solvent Selection Guide
Solvent class
Solvent
Boiling
point
Water
solubility
Safety
Health
Env
(air)
Env
(water)
Env.
(waste)
Hydrocarbon
Hydrocarbon
Hydrocarbon
Aromatic
Aromatic
Aromatic
Halogenated
Halogenated
Halogenated
Ester
Ester
Ester
Ether
Ether
Ketone
Alcohol
Alcohol
Alcohol
Cyclohexane
Heptane
Hexane
Benzene
Toluene
Xylenes
Chlorobenzene
Chloroform
Dichloromethane
Ethyl acetate
Isobutyl acetate
Isopropyl acetate
Ethyl ether
Tetrahydrofuran
Acetone
Ethanol
Ethylene glycol
Methanol
  81°C
  98°C
  69°C
  80°C
110°C
~140°C
131°C
  61°C
  40°C
  70°C
118°C
  89°C
  35°C
  66°C
  57°C
  79°C
197°C
  65°C
0.05 g/L
Insoluble
Insoluble
1.8 g/L
0.5 g/L
Insoluble
0.5 g/L
8 g/L
13 g/L
83 g/L
7 g/L
43 g/L
69 g/L
Miscible
Miscible
Miscible
Miscible
Miscible
6
6
6
5
5
4
3
2
2
5
5
3
9
5
4
4
3
3
5
4
7
10
7
4
5
9
7
4
3
4
5
6
4
3
3
5
4
4
5
6
6
4
5
7
9
6
5
6
7
5
7
5
5
6
7
7
8
6
6
7
8
7
6
4
2
3
4
4
1
1
1
3
2
2
1
2
2
3
6
6
7
4
2
3
4
5
5
6
7
6
The information in this table was compiled from The Merck Index, 11th ed., and the ACS GCI Pharmaceutical
Roundtable Solvent Selection Guide Version 2.0 Issued March 21, 2011: http://www.acs.org/content/acs/en/
greenchemistry/industriainnovation/roundtable.html.
26
Part 1
Introduction to the Organic Laboratory
with them to lower the energy required to break and form new
bonds, thus speeding up reactions and allowing lower temperatures
to be used. Particularly useful are catalysts that can tolerate safer
solvents, such as water or methanol, and that can be reused, saving
resources and money. Chemists play important roles in developing greener processes by designing, synthesizing, and testing new
catalysts.
Over the past 10 years, industry has embraced biological
catalysts in the large-scale production of chemical feedstocks and
fine chemicals. Selective enzyme-based catalysts are now used to
produce pharmaceutical, cosmetic, and food products. These often
function under mild conditions and in water solution, allowing
for energy savings and reduced waste. Fermentation processes
that capitalize on the enzymes in yeast are also widely used in
industry, particularly for preparing biorenewable feedstocks from
biomass.
The Dow Chemical Company and BASF won a 2010 Presidential
Green Chemistry Challenge Award for the production of propylene
oxide by oxidation of propylene with hydrogen peroxide. Propylene oxide is a bulk commodity chemical used for making foam seat
cushions and mattresses, detergents, and personal care products.
The oxidation of propylene traditionally uses bleach or organoperoxides for this process. Bleach is made industrially from highly toxic
and reactive chlorine gas. Organoperoxides are very reactive and the
oxidation generates organic waste that needs to be recycled, which
consumes extra energy (see reaction A below). The new process
uses hydrogen peroxide, which is safer to handle, produces harmless water as waste, and requires less energy (see reaction B below).
These benefits depend on the discovery of a catalyst that can activate hydrogen peroxide.
Less Hazardous
Chemical Syntheses
A. Organoperoxide process:
H
H2C ” C
CH3
CH3
H
C
+ 3
C
OH
O
H3C
Propylene
MW = 42
catalyst A
Tert-butyl hydroperoxide
MW = 90
O
H2C
CH
CH3
CH3
H3C C
+
OH
H3C
Propylene oxide
MW = 58
Tert-butyl alcohol
(waste)
B. Hydrogen peroxide process:
H
+
H 2C ” C
HO
OH
CH3
Propylene
MW = 42
Atom Economy
Hydrogen peroxide
MW = 34
catalyst B
O
H2C
CH
CH3
Propylene oxide
MW = 58
+ H 2O
Water
(waste)
Atom economy is a quantitative measure of how efficiently atoms of
the starting materials and reagents are incorporated into the desired
product. It represents the percentage of atomic mass of the starting
materials that end up in the final product, assuming 100% yield in
Chapter 2
27
Green Chemistry
the reaction. The balanced equation for a reaction is used in the calculation of atom economy:
sum(MWproducts)
_______________
atom economy 5 ​   
   ​ 3 100%
sum(MWreagents)
It may be obvious that the Dow-BASF hydrogen peroxide process
is more atom economical than the organoperoxide process, but the
atom economy calculation enables this improvement to be quantified
and compared with other alternatives. Here are the calculations for
the organoperoxide (A) and hydrogen peroxide (B) processes:
MWpropylene oxide
______________________________
atom economy (A) 5 ​     
    ​ 3 100%
MWpropylene 1 MWt-butyl hydroperoxide
58
 ​ 3 100% 5 44%
5 _______
​ 
42 1 90
MWpropylene oxide
____________________________
atom economy (B) 5 ​    
    ​ 3 100%
MWpropylene 1 MWhydrogen peroxide
58
 ​ 3 100% 5 76%
5 _______
​ 
42 1 34
Reaction Efficiency
The concept of reaction efficiency was developed as a measure of
the mass of reactant atoms actually contained in the final product.
Suppose you had developed a catalyst that performs the hydrogen
peroxide process but in only 55% yield, and the established organoperoxide process (A) occurs with 99% yield. Would it be worthwhile
to switch to the hydrogen peroxide process? The reaction efficiency
can help answer this question, as shown in the following equation:
reaction efficiency 5 % yield 3 atom economy
reaction efficiency (hypothetical HOOH process) 5 55% 3 0.76 5 42%
reaction efficiency (organoperoxide process) 5 99% 3 0.44 5 44%
The reaction efficiency indicates that only 42% of the mass of
reactants would be recovered as product with your hypothetical
catalyst, whereas 44% is transformed to product in the organoperoxide process. With your low-yielding process, it may not be worthwhile to switch. The Dow-BASF catalyst, however, is significantly
higher yielding, making the hydrogen peroxide process superior.
Use of Renewable
Feedstocks
The Dow-BASF synthesis described above is an important step
toward greening an industrial process; however, the propylene
feedstock originates from petroleum. Inventive chemists at the
2009 start-up company XL Terra, Inc. have developed a new plastic
from biomass that has functional properties comparable to plastics
made from petroleum. This plastic, Poly(Xylitan Levulinate Ketal)
(PXLK), is made from a five-carbon carbohydrate (xylose) isolated
from nonfood biomass, such as corn cobs or wood waste. After use,
28
Part 1
Introduction to the Organic Laboratory
the plastic can be treated to recover and re-use the starting materials
or left to biodegrade harmlessly. This is one example among many
new chemical technologies that are being developed to replace petrochemical feedstocks with biorenewable feedstocks.
The overall yield for a process is the product of the yields of each individual step; therefore, introducing additional steps in a process may
diminish the yield. For example, if each step in a two-step synthesis
occurred in 98% yield, the total overall yield would be (0.98 3 0.98) 5
0.96, or 96%. If the transformation involved six steps, each occurring
in 98% yield, the overall yield would be only (0.98)6 5 0.88, or 88%.
The effect of the number of steps on the efficiency of a process
is shown by the synthesis of the common analgesic ibuprofen. The
classic six-step route was developed at the Boots Pure Chemical
Company, where ibuprofen was discovered. Several steps introduce
carbon atoms that must be removed later and treated as waste. A
greener route was developed by Boots-Hoechst-Celanese (BHC);
it has only three steps, two of which have 100% atom economy. If
each of these steps occurred in 98% yield, the overall yield would
be (0.98)3 5 0.94, or 94%. In reality, the yield for each step is higher.
The only waste that is generated is acetic acid in the first step.
Anhydrous hydrogen fluoride is both a catalyst and a solvent in the
first step, but it is recovered and recycled with greater than 99.9%
efficiency. Hydrogen fluoride is a very hazardous material and no
doubt researchers are striving to develop safer alternatives. This
Presidential Green Chemistry Challenge Award-winning process
is commercialized and a Texas plant produces about 4000 tons of
ibuprofen per year using this route.
Synthetic Efficiency
Boots-Hoechst-Celanese Process:
O
O
O
CH3CO2H
waste
HF (catalyst
and solvent)
CO2H
OH
O
CH3
H2
Pd(C)
(catalyst)
CH3
CH3
CO
Pd(II), PPh3
(catalyst)
Ibuprofen
2.3
Green Principles Applied to Academic
Laboratories
Apart from pedagogical or experimental value, the greatest concern
in an academic laboratory is student safety. Experimental modifications that minimize student exposure to chemical hazards, reduce
chemical waste, and decrease the need for safety equipment, such
as fume hoods, have a high priority. Over the past 15 to 20 years,
the single greatest change in instructional laboratories has been to
reduce the scale of reactions performed by students. This lowers the
potential for student exposure to chemical hazards and the amount
of hazardous waste that is generated.
Chapter 2
29
Green Chemistry
Safer Solvents
Just as in industry, academic laboratories are adapting to use solvents
that pose fewer health and environmental hazards, such as water or
ethanol, or that eliminate the need for solvents altogether. When a
desired product can be isolated from mixtures by simple filtration,
distillation, or sublimation, students do not need to handle flammable (ether) or possibly carcinogenic (dichloromethane) solvents in
the laboratory. However, there are situations when it is impossible
to separate an organic product without using an organic solvent.
Below…