CHEM 333:
University of Illinois
at Chicago
Advanced Synthetic Laboratory
UIC
Advanced Synthetic
Laboratory (CHEM 333)
Lecture 2
Instructor: Dr. Chad Landrie
Lecture CRN: 17450
TR, 2:00-2:50 pm
June 14, 2012
Fischer Esterification IS Reversible!!
O
O
OH
O
EtOH
H2N
H2SO4
CH3
+ H2O
H2N
p-aminobenzoic acid (PABA)
benzocaine
Pitfalls Previous Semesters:
95% Ethanol = 5% Water
9 M H2SO4 = 9 mol H2SO4/1 L water
Completion = Solution turns clear (TLC??)
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 2
Lecture: June 14
Benzocaine Synthesis: Intermediates & Solubility
O
O
OH
H2SO4
O
OH
H2N
HSO4 H3N
PABA•H2SO4
O
EtOH
p-aminobenzoic acid (PABA)
benzocaine
Water Insoluble
Na2CO3
H2SO4
O
O
O
O
Na
H2N
Water Soluble
CH3
HSO4 H3N
sodium p-aminobenzoate
UIC
+ H2O
H2N
H2SO4
Na2CO3 (aq)
(10% w/w)
University of
Illinois at Chicago
CH3
benzocaine•H2SO4
Water Soluble
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 3
Lecture: June 14
TLC Can Indicate Reaction Progress
Elutropic Series (pg 182)
RCO2H > ROH > RNH2 > RR’C=O > RCO2R’ > ROR’ > C=C > R-X
O
O
OH
H2N
SM
CS RXN
UIC
CH3
H2N
SM
No reaction progress OR
No separation
University of
Illinois at Chicago
O
is more polar than
CS RXN
Partial reaction progress
SM
CS RXN
Reaction complete
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 4
Lecture: June 14
CHEM 333:
University of Illinois
at Chicago
Advanced Synthetic Laboratory
UIC
Quick Review of
Infrared
Spectroscopy
Text: pp. 237-256
Spectroscopy vs. Spectrometry
Spectroscopy = study of the interaction of
electromagnetic radiation with matter; typically
involves the absorption of electromagnetic radiation
Spectrometry = evaluation of molecular identity
and/or properties that does not involve interaction
with electromagnetic radiation
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 6
Lecture: June 14
Electromagnetic Spectrum
shorter wavelength (λ)
higher frequency (ν)
higher energy (E)
longer wavelength (λ)
lower frequency (ν)
lower energy (E)
Electromagnetic Radiation
• propagated at the speed
of light (3 x108 m/s)
• has properties of particles
and waves
• energy is directly
proportional to frequency
• energy is indirectly
proportional to
wavelength
E = hν
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
c = νλ
Slide 7
Lecture: June 14
Spectroscopic Methods
Method
Measurement/Application
Infrared
Spectroscopy
• vibrational states: stretching and bending frequencies
of covalent bonds that contain a dipole moment
• functional group determination
Ultraviolet-Visible • electronic states: energy associated with promotion
(UVof an electron in a ground state to an exited state
vis )Spectroscopy • chromophore determination
Mass
Spectrometry
• molecular weight: of parent molecule and fragments
produced by bombardment with “free” electrons
• fragment and isotope determination
Nuclear Magnetic • nuclear spin states: energy associated with spin states
Resonance
of nuclei in the prescence of a magnetic field
Spectroscopy • determine structural groups and connectivity
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 8
Lecture: June 14
Quantized Energy States
Types of
States
Increasing Energy
radiofrequency
nuclear spin
1-10 m
rotational
UIC
microwave
10-100 cm
infrared
vibrational
0.78-1000 μm
electronic
University of
Illinois at Chicago
Energy
Range (λ)
ultraviolet
800-200 nm
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Spectroscopic
Method
NMR
Microwave
IR
UV-vis
Slide 9
Lecture: June 14
Review: Principles of Infrared Spectroscopy
IR: Measures the vibrational energy associated with stretching
or bending bonds that contain a dipole moment (µ).
Stretching
δ+
δ−
δ+
δ−
δ+
δ−
Bending
δ−
δ−
δ+
University of
Illinois at Chicago
UIC
δ+
δ−
δ+
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 10
Lecture: June 14
Stretching & Bending Vibrations
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 11
Lecture: June 14
Dipole Moment
more
electronegative
atom
covalent 2
electron bond
dipole arrow
δ
less
electronegative
atom
δ
(partially negatively charged)
(partially positively charged)
In order to measure the stretching or bending frequency
of a covalent bond, it must have a dipole moment (μ).
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 12
Lecture: June 14
Hooke’s Law: Bonds are Like Springs
Vibrational Energy Depends both on bond strength (spring
force constant) and the mass of atoms (objects) attached
Trends:
↑ bond strength =
↑ frequency
~
ν = vibrational “frequency” in wavenumbers (cm-1)
k = force constant; strength of bond (spring)
m* = reduced mass
↑ mass =
↓ frequency
ma = mass of 1 atom of a
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 13
Lecture: June 14
Spring Analogy
smaller mass =
higher frequency =
higher energy
University of
Illinois at Chicago
UIC
stronger spring (bond) =
higher frequency =
higher energy
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 14
Lecture: June 14
Wavenumber (ῡ) and Infrared Scale
ῡ
(cm-1)
1
=
λ (cm)
higher wavenumber (ῡ) =
higher frequency (υ) =
lower wavelength (λ) =
higher energy (E)
N-H O-H
3400
lower wavenumber (ῡ) =
lower frequency (υ) =
longer wavelength (λ) =
lower energy (E)
C(sp)-H
C(sp2)-H
C(sp3)-H
3000
CO2
(2380)
2600
C
N
C C
2200
C
O
C
C
1800
C
fingerprint
region
C O
N
1400
1000
wavenumber (cm-1)
wavenumber = reciprocal of the wavelength measured
in centimeters (cm); directly proportional to frequency
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 15
Lecture: June 14
Common IR Units: Wavenumber (cm-1) &
Micrometer/”Micron” (µm)
Example: Convert 2,500 wavenumbers (cm-1) to microns (µm).
1 cm
2,500
x
1m
100 cm
x
106 µm
1m
=
10,000
2,500
=
4 microns (µm)
Example 2: Convert 2.5 microns (µm) to wavenumbers (cm-1).
1
2.5 µm
x
106 µm
1m
x
1m
100 cm
=
10,000
2.5
=
4000 cm-1
Wavenumber is a convenient unit since it is directly
proportional to energy and not as large as units of Hz (1/s).
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 16
Lecture: June 14
Functional Group Identification
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 17
Lecture: June 14
General Need-to-Know IR Frequencies
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 18
Lecture: June 14
Infrared Spectrum
100
% Transmission
80
60
Transmittance: amount of light
that passes through sample; not
absorbed by molecular vibrations
40
Frequency: typically measured in
wavenumbers; higher wavenumber =
higher frequency = higher energy
vibration
20
4000
University of
Illinois at Chicago
3500
UIC
3000
Bands: frequency of vibration
absorbed by molecules; can be broad
or narrow; number of bands does
not equal number of bonds
2500
2000
Wavenumbers
1500
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
1000
500
Slide 19
Lecture: June 14
Example: Alkanes
3
100
1
1
2
80
C
H2
3
H H
C
H
40
20
3500
University of
Illinois at Chicago
3000
UIC
2500
2000
Wavenumbers
1500
1000
H
C
C
H
CH3
C
H H
hexane
60
4000
H
H
2
• 2 = sp3 C-H bond stretching
motion; general absorb
around 2850-2950 cm-1
• 1 = C-H rocking motion
when C atom is part of a
methyl group (-CH3);
1370-1350 cm-1
• 3 = scissor motion of -CH3
hydrogen atoms; 1470-1450
cm-1
• 1300-900 cm-1 = fingerprint
region for organic
500 molecules; typically complex
and unhelpful
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 20
Lecture: June 14
Example: Alkenes
H
100
H H
C
C
H3C
C
H
80
5
4
H
H
4
• 5: notice sp2 C-H (~3100
cm-1) at higher frequency
than sp3 C-H (~2950 cm-1)
• more s-character = stronger
bond = higher frequency
40
• 4: also, C=C bond at higher
frequency than C-C bond;
~1600 cm-1
20
University of
Illinois at Chicago
C
C
H
5
1-hexene
60
4000
H
H
3500
3000
UIC
2500
2000
Wavenumbers
1500
1000
500
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 21
Lecture: June 14
Example: Alkynes
6
6
C
H3C
7
H
C
7
1-hexyne
• 7: notice sp C-H (~3300
cm-1) at higher frequency
than sp2 C-H (~3100 cm-1),
which was higher than sp3
C-H (~2950 cm-1)
• 6: C≡C stretch is very
weak because carbons have
almost identical
electronegativities = small
dipole moment
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 22
Lecture: June 14
Example: Alcohols
100
H
H
C
O
9
4
80
H
H
5
C
H
C
H
4
prop-2-en-1-ol
(allyl alcohol)
5
60
• 9: hydroxyl groups (-OH)
exhibit strong broad bands;
~3300 cm-1
40
• broad peak is a result of
hydrogen bonding; width
depends on solution
concentration
20
4000
University of
Illinois at Chicago
9
3500
• lower concentration = less
hydrogen bonding = more
narrow -OH band
3000
UIC
2500
2000
Wavenumbers
1500
1000
500
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 23
Lecture: June 14
Example: Nitriles
100
9
H
C
O
8
80
N
8
3-hydroxy-propionitrile
• 8: nitriles ~2200 cm-1
60
• nitriles (C≡N) absorb a
greater magnitude of energy
than alkynes (C≡C)
because they have a larger
dipole moment
40
9
• larger dipole moment =
more intense peak
20
• size of the dipole does NOT
affect frequency of vibration
4000
University of
Illinois at Chicago
3500
3000
UIC
2500
2000
Wavenumbers
1500
1000
500
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 24
Lecture: June 14
Example: Ester, Amine, Benzene
100
O
10
C
C
O
4
C
H
N
80
H
11
2-amino-benzoic acid butyl ester
60
• 10: strong carbonyl (C=O)
band ~1700 cm-1
40
• 11: amines; secondary
amines (-NH) give one
band; primary amines (NH2) gives two bands
11
10
20
4000
• 4: several alkene bands
~1600 cm-1 for benzene ring
C=C double bonds
4
3500
University of
Illinois at Chicago
3000
UIC
2500
2000
Wavenumbers
1500
1000
500
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 25
Lecture: June 14
Example: Carboxylic Acid
O
100
4
9
10
C
H
O
9
C
C
5
80
H
H
4
cyclohex-2-enecarboxylic acid
• 10: strong carbonyl (C=O)
band ~1700 cm-1
60
• 9: hydroxyl band (-OH) can
be less intense and sharper
in carboxylic acids
40
• 4: weak alkene band (C=C)
since small dipole moment
10
20
4000
3500
University of
Illinois at Chicago
3000
UIC
2500
2000
Wavenumbers
1500
1000
500
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 26
Lecture: June 14
Example: Aldehyde
100
H
O
C
C
C
4
4
80
H
12
hept-2-enal
12
60
• 12: usually two bands for
C-H of aldehydes; may
overlap with sp3 C-H bands
(Fermi doublet)
40
10
20
4000
H
10
3500
University of
Illinois at Chicago
3000
UIC
2500
2000
Wavenumbers
1500
1000
500
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 27
Lecture: June 14
Example 1
O
OH
H3C
cyclobutanol
University of
Illinois at Chicago
CH3
2-butanone
UIC
O
H2C
H2C
O
CH3
ethyl vinyl ether
OH
CH3
2-methyl-2-propen-1-ol
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
H
2-methylpropanal
Slide 28
Lecture: June 14
Example 1: 2-butanone
O
OH
H3C
cyclobutanol
University of
Illinois at Chicago
CH3
2-butanone
UIC
O
H2C
H2C
O
CH3
ethyl vinyl ether
OH
CH3
2-methyl-2-propen-1-ol
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
H
2-methylpropanal
Slide 29
Lecture: June 14
Example 2
O
OH
H3C
cyclobutanol
University of
Illinois at Chicago
CH3
2-butanone
UIC
O
H2C
H2C
O
CH3
ethyl vinyl ether
OH
CH3
2-methyl-2-propen-1-ol
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
H
2-methylpropanal
Slide 30
Lecture: June 14
Example 2: Cyclobutanol
O
OH
H3C
cyclobutanol
University of
Illinois at Chicago
CH3
2-butanone
UIC
O
H2C
H2C
O
CH3
ethyl vinyl ether
OH
CH3
2-methyl-2-propen-1-ol
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
H
2-methylpropanal
Slide 31
Lecture: June 14
Example 3
O
OH
H3C
cyclobutanol
University of
Illinois at Chicago
CH3
2-butanone
UIC
O
H2C
H2C
O
CH3
ethyl vinyl ether
OH
CH3
2-methyl-2-propen-1-ol
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
H
2-methylpropanal
Slide 32
Lecture: June 14
Example 3: 2-Methyl-2-propen-1-ol
O
OH
H3C
cyclobutanol
University of
Illinois at Chicago
CH3
2-butanone
UIC
O
H2C
H2C
O
CH3
ethyl vinyl ether
OH
CH3
2-methyl-2-propen-1-ol
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
H
2-methylpropanal
Slide 33
Lecture: June 14
Example 4
O
OH
H3C
cyclobutanol
University of
Illinois at Chicago
CH3
2-butanone
UIC
O
H2C
H2C
O
CH3
ethyl vinyl ether
OH
CH3
2-methyl-2-propen-1-ol
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
H
2-methylpropanal
Slide 34
Lecture: June 14
Example 4: Ethyl vinyl ether
O
OH
H3C
cyclobutanol
O
H2C
CH3
2-butanone
H2C
O
CH3
ethyl vinyl ether
OH
CH3
2-methyl-2-propen-1-ol
H
2-methylpropanal
Greater s
character =
stronger, shorter
bonds = higher
frequency
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 35
Lecture: June 14
Example 5
O
OH
H3C
cyclobutanol
University of
Illinois at Chicago
CH3
2-butanone
UIC
O
H2C
H2C
O
CH3
ethyl vinyl ether
OH
CH3
2-methyl-2-propen-1-ol
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
H
2-methylpropanal
Slide 36
Lecture: June 14
Example 5: 2-Methylpropanal
O
OH
H3C
cyclobutanol
University of
Illinois at Chicago
CH3
2-butanone
UIC
O
H2C
H2C
O
CH3
ethyl vinyl ether
OH
CH3
2-methyl-2-propen-1-ol
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
H
2-methylpropanal
Slide 37
Lecture: June 14
Application
Place the molecules in order of increasing IR
absorption frequency for the C=O stretch.
O
O
OH
Et
N
Et
OH
F3C
O
O
OH
OH
H3C
HO
O
OH
O2N
O
1
1668 cm-1
University of
Illinois at Chicago
2
5
UIC
1698 cm-1
1676 cm-1
3
1682 cm-1
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
4
1697 cm-1
Slide 38
Lecture: June 14
Application
O
O
O
H
O
H
H2N
H2N
•
O-H bond much weaker
than O-C bond =
•
greater electron density
on oxygen =
•
more resonance
contribution =
•
•
weaker carbonyl bond =
1662 cm-1
(C=O)
O
O
O
CH3
H2N
H2N
1685 cm-1
(C=0)
University of
Illinois at Chicago
O
UIC
CH3
lower vibrational
frequency
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 39
Lecture: June 14
Attenuated Total Reflectance
solid or liquid sample
effanescent wave
(0.5 - 5 µm)
total reflection
high refractive index crystal
(e.g. ZnSe, Ge, Diamond)
attenuated
infrared beam
to detector
infrared beam
from source
• evanescent wave = decays exponentially
• energy of the evanescent wave is attenuated
(reduced) by absorption of characteristic
vibrational frequencies
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 40
Lecture: June 14
ATR Accessory
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 41
Lecture: June 14
ATR Intensity Correction
Click on “ATR”
University of
Illinois at Chicago
UIC
•
ATR spectra are not identical
to transmission spectra
•
ATR: lower intensity at higher
wavenumbers
•
ATR: slight (1-2 wavenumber)
shift in absolute frequency
toward lower wavenumbers
•
JASCO software corrects only
for intensity
•
Thermo software does not do
any ATR correction (not
available in our lab)
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 42
Lecture: June 14
Homework Continued
2.
Explain why the C=O stretch is generally lower in amides compared to carboxylic acids or esters. Draw
resonance structures to support your answer.
3.
Why is no IR absorption visible for the C≡C bond in dibenzyl acetylene?
4.
The widths of O-H IR peaks vary from broad to sharp. Explain this observation? Which sample preparations/
conditions give rise to broad and sharp O-H peaks?
5.
Draw a complete mechanism for Fischer Esterification of PABA with isopropyl alcohol.
6.
Draw a complete mechanism for the acid catalyzed hydrolysis of benzocaine.
7.
Using only structural formulas (Lewis structures), draw the complete reaction between sodium carbonate and
sulfuric acid.
8.
In the Fischer esterification of PABA to benzocaine, why was sodium carbonate used to neutralize excess
sulfuric acid after the reaction rather than sodium hydroxide?
9.
Using Hooke’s Law, calculate the wavenumber for a C-H bond, then for a C-D bond. Use the estimated k value
for a single bond listed in your textbook on page 240 (5 x 105 dyne•cm–1).
10. The C=O IR stretch for aromatic esters is generally lower (1730-1715 cm-1) than for aliphatic esters (1750-1730
cm-1). First, explain this observation. Second, explain why the C=O IR stretch for benzocaine--an aromatic
ester--is lower (1685 cm-1) than either range.
11. Explain why C(sp)-H stretches absorb at higher IR frequencies than C(sp2)-H stretches. Based on your
reasoning, how do you explain the fact that C(sp)-H hydrogens are more acidic (pKa ~ 25) than C(sp2)-H
hydrogens (pKa ~ 45), which are more acidic than C(sp3)-H (pKa ~ 62)? Are these contradictory ideas?
University of
Illinois at Chicago
UIC
© 2012, Dr. Chad Landrie
CHEM 333: Advanced Synthetic Chemistry
Slide 43
Lecture: June 14