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CEM 255: Organic Laboratory
Spring 2015
Lecture: Thursday 4:10 – 5:00 pm
N130 BCC
Instructors: Dr. Ardeshir Azadnia
Office: 128 Chemistry
Email: azadnia@chemistry.msu.edu
Office hours: Mondays and Thursdays 10 - 11:30 am or
by appointment
Mr. Dave Voss
Office: 134 Chemistry
Email: voss@chemistry.msu.edu
Office hours: by appointment
Class Website:
http:// www2.chemistry.msu.edu/courses/cem255/
Required Materials
Lab Text:
“CEM 255 Organic Chemistry Laboratory Manual – 7th Edition",
A. Azadnia, Hayden- McNeil Publishing, Inc., 2013
Safety Supplies: Approved splash proof safety goggles (ANSI 279.1 1979) and
rubber "dish washing" gloves. A rubber or plastic apron is also encouraged.
Supplementary Readings:
A 251-252 text, Any Organic Chemistry Text
Miscellaneous: Any bound notebook with duplicate pre-numbered pages and
carbon paper (comes as a bundle with the lab manual). The perforated
carbon copies will be torn out and submitted at the end of each lab. Also, a
ballpoint pen (not pencil) is needed for lab reports.
Course Description:
Material covered in lecture courses is based on experimental data accumulated
over the years, which has been systematized into natural laws and theories.
However, the study of chemistry (or any science) requires that you learn some
laboratory techniques and methods of data acquisition. It is intended that the skills
acquired in this course will be of practical value to you in your fields of interest. It is
hoped that a "hands on" experience also will enable you to grasp the concepts
presented in CEM 252 lecture more readily.
Office Hours: by appointment, voss@chemistry.msu.edu
Lecture Time:
Thursdays 4:00–4:50 PM, Room N130 Business College Complex
Grading
Experiments will be graded according to the weight scale on the schedule below.
Major or continual violations of safety rules will result in dismissal from lab without any points
and/or reduction of grade by 50 points per occurrence.
The grades will be based on accuracy and completeness of recorded observations and data as well as
legibility (neatness counts).
The grading procedure for each experiment will be discussed in class during the Thursday lectures
(4:10-5 PM) prior to the corresponding lab.
Your final grade will be based on the total points earned as follow:
965-1060 = 4.0
890-964 = 3.5
816-889 = 3.0
742-815 = 2.5
636-741 = 2.0
All CEM 255 students must get trained on the 300 MHz NMR instrument by no later than Friday,
February 20, 2015. There will be a 45–point penalty for anyone who does not get trained/checked
out by the due date.
The sign-up sheets will be outside of room 125 Chemistry on Thursday, January 22, 2015.
Students with “pacemakers” MUST not enter room 125 due to the health hazards such
as DEATH, and therefore, would be excused from doing the NMR-training/check out.
See me in person immediately if you have a pacemaker.
Absences
Because our teaching staff is being used to capacity, there will be
NO MAKE-UP LABORATORY, except for special circumstances,
which will be decided on an individual basis. If you are unavoidably
absent from a laboratory class due to illness or family crisis, contact
Dr. Azadnia as soon as possible. A grade of zero will be assigned for
an experiment missed regardless of the reason. However, you may
be allowed to make up the missed lab so long as you make
arrangement with Dr. Azadnia within one week of the corresponding
experiment.
Students who miss three or more sessions due to illness, etc.
should drop CEM 255 and re-enroll another term. Incomplete grades
CANNOT be issued when three or more labs have been missed. If
you drop CEM255 course, you still must be checked out of lab by
your lab TA, on or before your last scheduled lab section. Failure to
check out properly costs $25.00 plus breakage charges. No CEM
255 lockers will be shared. If you believe someone has access to
your locker, exchange your lock at the stockroom (room 133).
Write-ups
Your Lab Manual is not to be used in the lab. You must work from
your own procedures written in your lab notebook.
An important laboratory skill is the making and writing down of
precise observations. A well-kept notebook is an essential part of any
investigation. Your notebook should be a complete description of what
happened, or didn't happen, in your experiments. If someone else
could repeat your experiment and get identical results using only the
notebook for directions, then your notes are thorough. A well-kept set
of records is an essential part of any investigation. Take notes as if you
expected to repeat the work next term using only your own notes.
Before entering the laboratory, you should familiarize yourself with
the experiment by studying the Lab Manual and the corresponding
chapter in your organic textbook. Experience has shown that those
students who rewrite the procedure as numbered, single operation
steps directly in their notebooks encounter fewer problems. If this is
done in advance, then only observations and changes must be
recorded during the experiment. Keep track of your progress by
checking off the steps as you do them. Carbon copies of all prelab and
in-lab write-ups are to be submitted, along with any products, as you
leave the laboratory.
enroll another term. Incomplete grades CANNOT be issued when three or more labs have been missed.
If you drop the course, you still must be checked out of lab by your lab TA, on or before your last
scheduled lab– section. Failure to check out properly costs $25.00 plus breakage charges. No CEM 255
lockers will be shared.
Schedule
Week
1
2
3
4
5&6
7
8
9
10
11
12
13
14
DATE
1/22 – 2/14
1/19 –1/22
1/26 – 1/29
2/2 – 2/5
2/9 – 2/12
2/16 – 2/19
2/23 – 2/26
3/2 – 3/5
3/9 – 3/13
3/16 – 3/19
3/23 – 3/26
3/30 – 4/2
4/6– 4/9
4/13 – 4/16
4/20 – 4/23
4/27 – 4/30
Experiment
Value
NMR Training
90
NO CEM255 LABS (MLK Day)
Check-in/Models/mp Calibration
60
Thin Layer Chromatography
90
Distillation I
60
Extraction
60
Identification of an Organic Unknown
120
Distillation II: Preparation of Cyclohexene 120
SPRING BREAK, NO Labs
Acid I
Acid II
Acid III
120
Grignard Reaction
Grignard Reaction Work–up
120
Isolation of an Active Drug
60
Azo Dye/Check-out
60
FINAL EXAM – Thursday, April 30, 2015, 4:10-5:00 PM
Room N130 Business College Complex
100 pts.
Total
1060 pts.
There will be a 10–point of extra credit for lab clean–up on Friday, May 1, 2015 from 10 AM-4 PM.
You must work from your own procedures written in your lab notebook.
Write-ups
Laboratory Safety Regulations
SAFETY REGULATIONS
1. DRESS CODE
Firm footwear is required
(NO sandals, NO open-toed shoes)
Long pants that cover the entire leg must be worn at all
times (NO shorts, NO skirts)
Safety Goggles must
ALWAYS be worn in the lab
The dress code will be strictly enforced!
2. SAFETY EQUIPMENT
Every student MUST do all they can to prevent accidents in their own work
and they must be prepared for accidents by knowing in advance what
emergency aids are available.
Laboratory Safety Regulations
2. SAFETY EQUIPMENT
Every student MUST do all they can to prevent accidents in their own work and they must be
prepared for accidents by knowing in advance what emergency aids are available.
The laboratory is equipped with several type of safety equipment and it is essential that you
become familiar with the location and the operation of these tools.
a.
Emergency Shower: There is an emergency shower located on the hallway. It is for use
when corrosive liquids have spilled over large areas of clothes and skin, or when clothing is
on fire.
b.
Eye Wash Stations: The laboratory is equipped with eye wash stations. These stations
dispense water and provide thorough irrigation of the eyes and face in the event a person is
splashed with an irritating chemical. The contaminated body part should be rinsed for a
minimum of 15 minutes.
c.
Fire Extinguisher: The fire extinguisher is located outside the laboratory. Know its
location and how to operate it. It is very effective for fires involving organic liquids and
electrical fires. If a fire extinguisher is used it must be given to the laboratory coordinator for
recharging. Small fires in test tubes, beakers etc can usually be smothered by covering
with a watch glass.
In any case, REPORT all accident to your instructor immediately
Laboratory Safety Regulations
1. Absolutely NO EATING or DRINKING is permitted in the lab.
2. Waste Disposal
Please place the waste materials in the appropriate containers. If you are unsure,
make sure you ASK your instructor .
For this lab you should expect to have both solid and liquid waste containers, placed
separately in different containers inside the last fume hood.
Broken glassware belongs in the BROKEN GLASS bucket
Week 1
Melting Point Apparatus Calibration
Set at 3
Move to 4
Melting Point Apparatus Calibration Curve
200
Literature
value (oC)
0.2
0.0
Naphthalene
79.2
80.2
Benzoic Acid
121.7
122.24
Ice
Salicylic Acid
157.1
158.3
180
Literature Value (o C)
Observed
value (oC)
- 5 points
Full Credit
160
140
120
100
80
60
40
20
0
20
40
60
80 100 120 140 160 180 200
Observed Temperature (o C)
Using the Calibration Curve
200
Literature Value (o C)
180
160
143.2
140
120
100
80
60
40
20
145.7
0
20
40
60
80 100 120 140 160 180 200
Observed Temperature (o C)
und
cal
nf
ion
e
on
hat
an
six
ree
n
Figure 4.11 A ring-flip in chair cyclohexane interconverts axial and equatorial positions. What is axial in
cial to determining its properties and biological behavior.
the starting structure becomes equatorial in the ring-flipped structure, and what is equatorial in the starting
We know from Section 1.5 that ! bonds are cylindrically symmetrical. In
structure is axial after ring-flip.
other words, the intersection of a plane cutting through a carbon–carbon
single-bond orbital looks like a circle. Because of this cylindrical symmetry,
rotation is possible around carbon–carbon bonds in open-chain molecules. In
ethane, for instance, rotation around the
C ! C bond
occurs4.11,
freely,
constantly
As shown
in Figure
a chair
cyclohexane can be ring-flipped by keeping
changing the spatial relationships between the hydrogens on one carbon and
the middle four carbon atoms in place while folding the two end carbons in
those on the other (Figure 3.5).
opposite directions. In so doing, an axial substituent in one chair form becomes
an equatorial substituent in the ring-flipped chair form and vice versa. For
H
example, axial bromocyclohexane
becomes equatorial bromocyclohexane after
H
ring-flip. Since the energy barrier
to chair–chair interconversion is only about
C
C
H
H
H
45
kJ/mol (10.8 kcal/mol), H
the process
is rapid at room temperature and we see
Rotate
H
what appears to be a single structure rather than distinct axial and equatorial
H
H
C
C
isomers.
H
H
Molecular Models:
Conformational Isomers
H
The different arrangements of atoms that result from bond rotation are called
conformations, and molecules that have different arrangements are called conformational isomers, or conformers. Unlike constitutional isomers, however, different conformers often can’t be isolated because they interconvert too rapidly.
Conformational isomers are represented in two ways, as shown in Figure
3.6. A sawhorse representation views the carbon–carbon bond from an oblique
angle and indicates spatial orientation by showing all C ! H bonds. A Newman
projection views the carbon–carbon bond directly end-on and represents the
two carbon atoms by a circle. Bonds attached to the front carbon are Ring-flip
represented by lines to the center of the circle, and bonds attached to the rear carbon
are represented by lines to the edge of the circle.
Br
Back carbon
H
H
H
H
C
H
C
H
H
H
H
Axial bromocyclohexane
H
H
H
Front carbon
Br
Equatorial bromocyclohexane
molecule so that the fourth-ranked group ( " H) is oriented toward the rear,
away from the observer. Since a curved arrow from 1 ( " OH) to 2 ( " CO2H)
to 3 ( " CH3) is clockwise (right turn of the steering wheel), (!)-lactic acid
has the R configuration. Applying the same procedure to (#)-lactic acid
leads to the opposite assignment.
Molecular Models:
Stereoisomers
(a)
Figure 5.8 Assigning configuration
(b)
to (a) (R)-(!)-lactic acid and (b) (S)-(#)lactic acid.
H
H3C C
HO
H
CO2H
HO2C
2
1
H
CO2H
HO
C
CH3
3
R configuration
(–)-Lactic acid
2
HO2C
H
C
C
CH3
OH
1
OH
CH3
3
S configuration
(+)-Lactic acid
Further examples are provided by naturally occurring (!)-glyceraldehyde
and (#)-alanine, which both have the S configuration as shown in
Molecular Models:
Stereoisomers
5.10 | Chirality at Nitrogen, Phosphorus, an
Stereoisomers (Section 4.2) are compounds whose atoms are
connected in the same order but with a different spatial arrangement.
Among the kinds of stereoisomers we’ve seen are enantiomers, diastereomers, and cis–trans isomers of cycloalkanes. Actually, cis–trans isomers
are just a subclass of diastereomers because they are non–mirror-image
stereoisomers:
Enantiomers
(nonsuperimposable
mirror-image
stereoisomers)
CO2H
H3C
H
C
HO2C
HO
OH
(R)-Lactic acid
Diastereomers
(nonsuperimposable
non–mirror-image
stereoisomers)
H
H
Configurational
diastereomers
Cis–trans diastereomers
(substituents on same
H
HO
OH
CH3
CO2H
NH2
C
C
H
CH3
2R,3R-2-Amino-3hydroxybutanoic acid
H3C
H
CH3
(S)-Lactic acid
CO2H
NH2
C
C
C
H
2R,3S-2-Amino-3hydroxybutanoic acid
H3C
CH3
Molecular Models:
Meso Compounds
5.2 | The Reason for Handedness in Molecules: Chirality
145
Figure 5.4 and is achiral, while lactic acid, CH3CH(OH)CO2H, has no plane of
160
CHAPTER 5 | Stereochemistry at Tetrahedral Centers
symmetry in any conformation and is chiral.
Symmetry
plane
146
Not
symmetry
plane
Figure
5.4exists
The achiral
tartaric
acid
inpropanoic
three acid
stereoisomeric forms: two enantiomers a
molecule versus the chiral lactic acid
meso form.
molecule. Propanoic acid has a plane of
symmetry that makes one side of the
through the C2–C3 bond of mesomolecule a mirror image of the other
acid
the
molecule
side. Lactic acid has noHsuch symmetry
CHmakes
| 3
CHAPTER 5CH
Stereochemistrytartaric
at Tetrahedral
Centers
3
CO2H
HO
achiral.
plane.
H C H
H C OH
C
Symmetry plane
3 and 5. Thus, the C6–C5–C4 “substituent” is equivalent to the C2–C3–C4
subCO2H
Figure 5.11 A symmetry plane
CO2H
C reaching the same
stituent, and methylcyclohexane is achiral. Another way of
CO H
HO
conclusion is to realize that methylcyclohexane has a symmetry2 plane, which
H
passes through
OH the methyl group and through C1 and C4 of the ring.
The situation is different for 2-methylcyclohexanone. 2-MethylcycloCH3CH2CO2H
CH3CHCO2H
hexanone has
no symmetry plane and is chiral because C2 is bonded to four
Propanoic acid
Lactic acid
different groups:
a ! CH3 group, an ! H atom, a ! COCH2 ! ring bond (C1), and
(achiral)
a ! CH2CH2(chiral)
! ring bond (C3).
Some physical properties of the three stereoisomers are listed in Ta
The (!)- and (")-tartaric acids have identical melting points, solubilit
densities, but they differ in the sign of their rotation of plane-polarize
Symmetry
The most common, although not the
only, cause of chirality in an organic
The meso isomer, by contrast, is diastereomeric with the (!) and (") f
molecule is the presence of a tetrahedralplane
carbon atom bonded to four different
has no mirror-image relationship to (!)- and (")-tartaric acids, is a d
groups—for example, the central carbon atom in lactic acid. Such carbons are
compound altogether, and has different physical properties.
referred to as chirality centers, although other terms such as stereocenter, asymmetric center, and stereogenic center have also been used. Note that chirality is a
H CH
CH3 Properties of the Stereoisomers of Tartaric Acid
property of the entire molecule, whereas a chirality center
is 3the cause Table
of 5.3HSome
1
2 *
chirality.
O
Melting
Density
Solubility at 20
6
2
3
Detecting a chirality center in a complex molecule takes practice because it’s
1
3
°
Stereoisomer
point ( C)
[!]D
(g/cm )
(g/100 mL H2O
not always immediately apparent that four different groups
are 3bonded to a 4
5
6
168–170
1.7598
139.0
(!)
!12
given carbon. The differences don’t necessarily appear right next
to the chiral4
5
ity center. For example, 5-bromodecane is a chiral molecule because four differ168–170
1.7598
139.0
(")
"12
ent groups are bonded to C5, the chirality center (marked with an asterisk). A
Meso
146–148
0
1.6660
125.0
butyl substituent is similar to a pentyl substituent, but it isn’t identical. The
difference isn’t apparent until four carbon atoms away from the chirality cenMethylcyclohexane
2-Methylcyclohexanone
ter, but there’s still a difference.
(achiral)
(chiral)
Molecular Models:
Newman Projection
The extra 12 kJ/mol of energy present in the eclipsed conformation of ethane
is called torsional strain. Its cause has been the subject of controversy, but the
major factor is an interaction between C ! H bonding orbitals on one carbon with
antibonding orbitals on the adjacent carbon, which stabilizes the staggered conformation relative to the eclipsed one. Because the total strain of 12 kJ/mol arises
from three equal hydrogen–hydrogen
eclipsing
interactions, we can assign a
R
R
R
R
H R The
value of approximately 4.0
kJ/mol
(1.0
kcal/mol)
to
each
single
interaction.
R
H
H
H
R to rotation
R
barrier
that results can be represented on a graph of potential
energy
H
R
H
H
H
H
versus degree of rotation in which the angle between CH! H bonds
and
H on front
H
H
H
H
H
R
H
H
back carbons
H H as viewed end-on (the dihedral angle) goes full circle from 0 to 360°.
Staggered conformations,
Staggered and energy maxima
Eclipsedoccur at
Energy minima occur at staggered
Anti
eclipsed conformations, asGauche
shown in Figure
3.7.
Figure 3.7 A graph of po
Eclipsed conformations
energy versus bond rotatio
The staggered conformatio
12 kJ/mol lower in energy t
eclipsed conformations.
Energy
12 kJ/mol
H
H
H
H
H
H
0°
H
H
H
H H
H
H
60°
H
H
H
H
H
120°
H
H
H
H
H
H
H
180°
H
H
H
H
H
240°
H
H
H
H
H
H
H
300°
H
H
H
H
360°
H
Molecular Models:
Newman Projection
R
R
H
R
H
H
H
H
H
H
R R
R
H
H
H
R
H
H
H
R
Staggered
Gauche
Staggered
Anti
H
H R
H
H
H
R
H
H
Eclipsed
4.5 | Conformations of Cyclohexan
(a)
(b)
H
H
H
3
H
H
4
H
2
H
5
H 1
H
(c)
H
6
H
H
H
2
H
Observer
Figure 4.7 The strain-free chair conformation of cyclohexane. All C ! C ! C bond angles are 111.5°, close to
the ideal 109.5° tetrahedral angle, and all neighboring C ! H bonds are staggered.
The easiest way to visualize chair cyclohexane is to build a molecular model.
CH2
1
H
H
6
3
H
5
4
H
H
CH2
H
H
C
O
H
OH
H
O
H
O
H
O
Molecular Models:
Fischer
Projection
Depicting
Carbohydrate Stereochemistry: Fischer Projections
H
CH2OH
25.2 |
1003
D-Glyceraldehyde
A tetrahedral carbon atom is represented in a Fischer projection by two
crossed lines. The horizontal lines represent bonds coming out of the page, and
the vertical lines represent bonds going into the page.
Press flat
W
C
Y
Z
W
C
X
X
W
Y
Fischer
projection
For example, (R)-glyceraldehyde, the simplest monosaccharide, can be drawn
as in Figure 25.1.
C
CH2OH
Bonds
out of page
CHO
=
H
D-Ribos
carbonyl group has the same configuration as (R
projections.
Z
Z
Y
H
HO
CH2O
Figure 25.2 Some naturally occurring d sugar
X
CHO
[(R)-(+)-glyceraldehyde]
C
O
C
OH
In contrast with D sugars, L su
chirality center, with the bottom
projections. Thus, an L sugar is t
sponding D sugar and has the op
chirality centers.
H
CHO
=
H
CH2OH
OH
CH2OH
(R)-Glyceraldehyde
(Fischer projection)
Figure 25.1 A Fischer projection of (R)-glyceraldehyde.
Bonds
into page
HO
C
O
H
CH2OH
L-Glyceraldehyde
[(S)-(–)-glyceraldehyde]
CH2OH
CH2OH
Molecular Models:
Figurein
25.2
Some naturally
occurring d sugars. The # OH group at the chirality center farthest from the
Fischer
Projection
A tetrahedral
carbon
atom atom
is represented
a Fischer
projection
by two
A tetrahedral
carbon
is represented
in a Fischer
projection
by two
| Depicting
D-Ribose
D-Glucose
D-Fructose
25.2 25.2
Carbohydrate
Stereochemistry:
FischerFischer
Projections
1003 1003
| Depicting
Carbohydrate
Stereochemistry:
Projections
carbonyl group has the same configuration as (R)-(!)-glyceraldehyde and points toward the right in Fischer
crossed
lines. lines.
The horizontal
lines represent
bonds coming out of the page, and
crossed
The horizontal
lines represent
projections.bonds coming out of the page, and
the vertical
lines represent
bondsbonds
goinggoing
into the
the vertical
lines represent
intopage.
the page.
Press flat
Press flat
W
Y
C
X
W
Z
Y
C
In contrast with D sugars, L sugars have an S configuration at the lowest
chirality center, with the bottom # OH group pointing to the left in Fischer
Z
projections.
Thus, an LZsugar
Z is the mirror image (enantiomer) of the correZ
W sponding
C WX C XD sugar and
configuration from the D sugar at all
W has
X
W Xthe opposite
centers.
Ychirality
Y
Y
X
Z
Y
FischerFischer
projection
projection
Mirror
H
O can becan
O
For example,
(R)-glyceraldehyde,
the simplest
monosaccharide,
drawn
For example,
(R)-glyceraldehyde,
the simplest
monosaccharide,
be drawn H
C
C
as in Figure
25.1. 25.1.
as in Figure
HO
CHO CHO
H
HO
C
CHO CHO
H
Bonds Bonds
CH2OH
out of page
out of page
CHO CHO
L-Glyceraldehyde
= H = C HOHC =OH
C
HCH2OHCH OH
2
CH2OHCH OH
HO
2
=
H
[(S)-(–)-glyceraldehyde]
HOH
OH Bonds Bonds
into page
into page
CH2OHCH OH
2
(R)-Glyceraldehyde
(R)-Glyceraldehyde
(Fischer
projection)
(Fischer
projection)
HO
H
H
OH
O
H
HO
C
H
OH
H
HO
H
H
OH
HO
H
H
OH
CH2OH
L-Glucose
CH2OH
D-Glucose
(not naturally occurring)
FigureFigure
25.1 A 25.1
Fischer
of (R)-glyceraldehyde.
A projection
Fischer projection
of (R)-glyceraldehyde.
Note that the D and L notations have no relation to the direction in which a
given sugar rotates plane-polarized light. A D sugar can be either dextrorotatory
Because
a given
chiralchiral
molecule
can becan
drawn
in many
ways, ways,
it’s sometimes
Because
a given
molecule
be drawn
in many
it’s sometimes