Transcript Document

Lecture 17
• Hand in Lecture Problem 6
• The Synthetics
• Quiz 6 Review
Reminder: Quiz 6 in lecture on Thursday & Hand in Selection Sheet!
This Week in Lab:
• Finish Ch 9
• Ch 7 Final Report Due
• Ch 12 Progress Check
Note: This week’s office
hours are from 1 to 3 pm
on Wednesday.
Next Week in Lab:
• Start synthetics!
• Synthetic #1 PreLab Due
Ch 9 Final Report due the week of April 10th!
Natural Product Isolations
Experiment 110: Cholesterol from Human Gallstones
H3 C
H3 C
CH3
H
CH3
CH3
H
H
Cholesterol
MW 386.66
mp 148-149°C
H
HO
CH3
CH3
CH3
H3C
HO
H
H3C
H
H
• Extraction of cholesterol from gallstones using hot solvent
• Analyses: IR, NMR or MS
Cholesterol: Attached to lipoproteins HDL and LDL
• Average human has 200 g of cholesterol located in spinal cord,
brain, and nerve tissues
• May produce gallstones or cause hardening of the arteries
Natural Product Isolations
Experiment 112: Isolation of Casein, Lactose & Albumin from Milk
Casein: a phosphoprotein
Albumin: a globular, water-soluble protein
Lactose: a carbohydrate
Techniques used to isolate these 3 biomolecules:
• Precipitation of casein
• Separation of lactose & albumin by centrifugation
Analyses: Polarimetry of lactose
Natural Product Isolations
Experiment 116: Soap from Nutmeg
O
O
NaOH
H27HC3C
13
O
O
O
O
CH
C 3H
13
27
O
+
3
EtOH, H2O
H27HC3C
13
-
+
O Na
OH
HO
OH
Reflux 15 m in.
CH3H
C
13 27
Trimyristin
(a fat)
723.14 g/mol
mp 56-57΅C
Sodium myristate
(a soap)
228.36 g/mol
mp 58΅C
• Isolate trimyristin from nutmeg
• Saponify trimyristin to form sodium myristate, a soap
• Saponification = hydrolysis of an ester
• Analyses: chemical tests and IR or NMR
Glycerol
Reduction Reactions
Experiment 130: Hydrogenation of Olive Oil
CH2 O
C
(CH2)7
O
HC
(CH2)7CH3
C
CH2 O
(CH 2) 7CH 3
C
C
O
C
H
H
(CH2)7
10 % Pd/C
H
(CH 2) 7
O
C (CH2)16CH3
O
C C
H
O
CH2 O
(CH2)7CH3
C C
H
1
Gly cerol Trioleate
mp -5.5°C
MW 885.47
H
• Reduction of C=C bonds
• Quick look at mechanism in class
• Analyses: IR & NMR
H2
HC
O
C (CH2)16 CH3
O
CH2 O
C (CH2)16 CH3
O
2
Gly cerol Tristearate
mp 69.9°C
MW 891.52
Reduction Reactions
Experiment 135: Enzymatic Reduction: A Chiral Alcohol from a Ketone
• An asymmetric reaction!
• Quick look at a similar reduction mechanism in class
• Analyses: Polarimetry with IR or NMR
Substitution Reactions
Experiment 142: Synthesis of a Plant Hormone
Cl
O -
+
ClCH2CO2 -
Cl
• SN2 mechanism!
• Analyses: IR, NMR & MS
4-Chlorophenoxyacetic acid (2):
• Plant growth hormone
• Promotes growth of roots on plant clippings
• Prevents fruits from falling prematurely
OCH2CO2 -
H+
2
Substitution Reactions
Experiment 144: Synthesis of “OFF”
O
O
OH
St ep 1
+
CH3
SOCl2
Thiony l
chloride
3-Toluic acid
O
CH3
CH2 CH3
+
N
H
CH2 CH3
1st equivalent
diethylamine
+ SO2
+ HC l
CH3
Acid chloride
O
Cl
St ep 2
Cl
N
CH2 CH3
CH2 CH3 + H Cl
CH3
N, N-Diethyl -3-toluamide
CH2 CH3
H
N Cl H CH CH
2
3
CH2 CH3
N
H CH2 CH3
2nd equiv alent
Diet hy lamine
hydrochloride
Two-step process:
1. Make the acid chloride (mechanism not needed)
2. Make an amide from the acid chloride (acyl substitution reaction)
Analyses: IR, NMR, or GC/GC-MS
N,N-diethyl-m-toluamide (OFF):
Insect repellent
Substitution Reactions
Experiment 145: Synthesis of Norleucine
O
O
CH 2
CH 3
CH 2
CH 2
C
CH
NH 3
OH
Br
2-bromohexanoic acid
(-bromocaproic acid)
CH 2
CH 3
CH 2
CH 2
C
CH
NH 2
OH
+ Br -
d,l-norleucine
neutral form
O
CH 2
CH 2
C O
CH 3
CH 2
CH
+
NH 3 d,l-norleucine
zwitterionic form
• SN2 reaction - substitute Br with NH2
• Analysis: IR
Norleucine:
• Not a naturally occurring amino acid
• Structural isomer of leucine and isoleucine (both essential AAs)
Substitution Reactions
Experiment 146: Synthesis of Sulfanilamide
H
N
O
O
O
H
CH3
H
N
CH3
p-Acetaminobenzenesulfonyl chloride
MW 233.68
NH2
CH3
NH3
HSO3Cl
SO2Cl
Acetanilide
MW 135.16
mp 114°C
N
dil. HCl
SO2NH2
p-Acetaminobenzenesulfonamide
MW 214.25
SO2NH2
Sulfanilamide
MW 172.20,
mp 163-164°C
• Two substitution reactions plus a hydrolysis
• Analyses: Bioassay with IR or NMR
Sulfanilamide:
Inhibits growth of folic acid thus stopping the growth of bacteria
New PreLab Sections:
Chromatographic & Spectral
Features Comparisons
For the synthetic experiments only! See Chapter 10 for details!
Chromatographic Comparison
Relative Rf comparison between main organic starting material and main
product of reaction.
Example:
OH
Cyclohexanol
Starting material
Cyclohexene
Product
(Draw out structures)
Cyclohexanol would have a lower Rf value due to the OH functionality, which
is more polar than the alkene of cyclohexene.
PreLab Sections: Chromatographic & Spectral
Features Comparisons
For the synthetic experiments only!
Spectral Features Comparison
Consider diagnostic 1H NMR & IR signals for the starting material and product
that would be used to distinguish the two from one another.
Example:
OH
(Draw out structures)
Cyclohexanol
Starting material
Cyclohexene
Product
Cyclohexanol
Cyclohexene
Diagnostic 1H NMR
Signals
OH proton at 2-6 ppm,
singlet
=C-H (alkene) proton at
5-6.5 ppm, quartet or
multiplet (due to
complex splitting)
Diagnostic IR Signals
O-H stretch (broad) at
3600-3200 cm-1
C=C stretch at 1658 cm1
Comments on Synthetics
• May need to repeat an experiment.
• Yields count! The quality of your technique will be
evaluated.
• Check Chemical Inventory when looking for chemicals; check
hooded shelf, common shelf, refrigerators, ask class/TA,
or ask stockroom
• Get melting points for all solid products. Report yields for
all products.
• Do TLC analysis for appropriate reactions. TLC charts posted
throughout labs.
Troubleshooting
No product formed:
• No reaction - recovered starting material; verify by TLC
• Check reagent bottles
• Check times and temperatures
• Check calculations
Low yield after recrystallization:
Added too much solvent? Concentrate solution.
Obtain an oily-non-crystalline product? Try to recrystallize
product to get a solid.
Quiz 6 Review
Questions on:
• Basic theory of IR & NMR
• Data interpretation of IR & NMR data
May include annotating data
• Solving unknown structures using data
IR & NMR correlation charts will be provided.
Look over old lecture problems and lab guide/McMurry problems.
Spectroscopy
NMR (Nuclear Magnetic Resonance Spectroscopy):
•Uses radio waves (electromagnetic radiation)
•Interacts with sample’s nuclei in the presence of a magnet
•Effect: nuclei flip and relax (known as resonance)
1H
NMR:
Determine bond connectivities/pieces of a structure, whole structure
IR (Infrared Spectroscopy)
•IR radiation
•Interacts with molecule as a whole
•Effect: bond vibrations within molecule
IR Use:
Determine the functional groups present in a structure:
-OH, C=O, C-O, NH2, C=C, CC, C=N, CN
Quiz 6 Practice Problems
Propose a structure that is consistent with the following data.
C4H7BrO2
1H
NMR:
1.08 ppm (t, 3H)
2.07 ppm (m, 2H)
4.23 ppm (t, 1H)
10.97 ppm (s, 1H)
IR:
broad peak
2500-3000 cm-1
peak at 1705 cm-1
Quiz 6 Practice Problems
C7H8O 1H NMR:
2.43 ppm (s, 1H)
4.58 ppm (s, 2H)
7.28 ppm (m, 5H)
IR:
broad peak in 32003500 cm-1 region