GUIDED-INQUIRY
PROJECTS AND EXPERIMENTS
CHRISTINA NORING HAMMOND
VASSAR COLLEGE
POUGHKEEPSIE, NY
MONDAY LAB: Experiment 10
E2 ELIMINATION OF 2-BROMOHEPTANE:
INFLUENCE OF THE BASE
QUESTION: What effect does the bulkiness of the base have on the product
composition in the E2 debromination of 2-bromoheptane?
Br
NaOCH3 or
+
+
KOC(CH3)3
What is the product composition with each base?
•
Microscale procedure
•
Students work in teams of two with one using each base.
•
Product composition determined by GC analysis.
EXP. 8.1: RADICAL CHLORINATION REACTIONS
QUESTION: Do statistical factors determine the product composition in radical
chlorination reactions or do electronic factors play a role?
•
Green Chemistry: Cl2 is generated in situ from household bleach (5.25% NaOCl)
and 3 M HCl:
NaOCl + HCl
HOCl + HCl
•
Substrates used:
HOCl + NaCl
Cl2 + H2O
Cl
1-Chlorobutane
2,2,4-Trimethylpentane
•
Microscale experiment.
•
Teamwork.
•
Irradiation with 300-watt unfrosted incandescent bulb until the yellow color
of Cl2 disappears (~5 min).
•
Product mixture analyzed by GC.
EXP 8.2: PHOTOBROMINATION OF 1,2-DIPHENYLETHANE
QUESTION: Which diastereomer forms in the photobromination of
1,2-diphenylethane?
•
Green Chemistry: Bromine is generated in situ:
KBrO3 + 6 HBr
•
3 Br2 + 3 H2O + KBr
Irradiation done with 100-watt incandescent bulb for ~10 min.
H
Br
H
+ 2Br2
H
H
H
h
hexane
+ 2HBr
H
Br
meso mp 237΅C
racemic mp 111΅C
•
Product analyzed by m.p.
PROJECT 6: E1/E2 ELIMINATION REACTIONS
QUESTION: Compare the mixture of isomeric alkenes produced by an acidcatalyzed dehydration and a base-catalyzed dehydrochlorination.
Are the product ratios influenced primarily by product stability?
• Two-week project for a team of two students.
PROJECT 6: E1/E2 ELIMINATION REACTIONS
Project 6.1 Acid-Catalyzed Dehydration of 2-Methyl-2-butanol
QUESTION: Does product stability or do statistical factors determine the ratio
of 2-methyl-2-butene to 2-methyl-2-butene?
OH
H2SO4
+
What is the ratio of alkenes?
Project 6.2 Synthesis of 2-Chloro-2-methylbutane
PURPOSE: To synthesize 2-chloro-2-methylbutane for use in a
dehydrochlorination reaction.
OH
Cl
HCl
PROJECT 6: E1/E2 ELIMINATION REACTIONS
Project 6.3
Base-Catalyzed Dehydrochlorination of 2-Chloro-2-methylbutane
QUESTION: Does product stability or do statistical factors determine the ratio
of 2-methyl-2-butene to 2-methyl-2-butene?
• Both students run the reaction using product prepared in 6.2.
Cl
KOH
1-propanol
+
What is the ratio of alkenes?
Project 4
INTERCONVERSION OF 4-tert-BUTYCYCLOHEXANOL
AND 4-tert-BUTYCYCLOHEXANONE
QUESTION: What is the stereoselectivity of NaBH4 reduction of
4-tert-butylcyclohexanone?
Project 4.1
Green Chemistry: Sodium Hypochlorite Oxidation of 4-tert-Butylcyclohexanol
O
OH
NaOCl
acetic acid
acetone
4-tert-Butylcyclohexanol
mixture of cis and trans
4-tert-Butylcyclohexanone
• Rate of reaction dependent on rate of stirring.
• When is the reaction complete?
• Reaction monitored by TLC analysis using p-anisaldehyde visualization.
INTERCONVERSION OF 4-tert-BUTYCYCLOHEXANOL
AND 4-tert-BUTYCYCLOHEXANONE
Project 4.2
Sodium Borohydride Reduction of 4-tert-Butylcyclohexanone
H
OH
O
NaBH4
ethanol
and
OH
H
4-tert-Butylcyclohexanone
4-tert-Butylcyclohexanol
What is stereoselectivity?
• Reaction can be monitored by TLC.
• Product analysis by GC and/or NMR.
-trans isomer: axial proton on C with --OH at 3.5 ppm.
-cis isomer:
equatorial proton at 4.03 ppm.
PROJECT 12: BIOCHEMICAL CATALYSIS AND
THE STEREOCHEMISTRYOF BOROHYDRIDE REDUCTION
QUESTION: What the stereoselectivity in the sodium borohydride reduction of
benzoin to 1,2-diphenyl-1,2-ethanediol?
PROJECT 12.1
• Green Chemistry: Traditional catalyst, KCN, is replaced with thiamine.
• Benzoin condensation is first step in a three-step project.
O
O
H
thiamine
NaOH
OH
Benzoin
(2-Hydroxy-1,2-diphenylethanone)
PROJECT 12: BIOCHEMICAL CATALYSIS AND
THE STEREOCHEMISTRYOF BOROHYDRIDE REDUCTION
PROJECT 12.2
O
OH
ethanol
+ NaBH4
OH
OH
Benzoin
(2-Hydroxy-1,2-diphenylethanone)
1,2-Diphenyl-1,2-ethanediol
What is ratio of meso to racemic?
H3C
CH3
H3C
OCH3
O
O
H3C
OCH3
2,2-Dimethoxypropane
Cyclic acetal of
1,2-diphenyl-1,2-ethandiol
• Cyclic acetal analyzed by NMR.
PROJECT 12: BIOCHEMICAL CATALYSIS AND
THE STEREOCHEMISTRYOF BOROHYDRIDE REDUCTION
• NMR analysis by chemical shifts of the -CH3 groups and the methine protons.
Ph
Ph
O
CH3
O
Ph
O
O
CH3
CH3
CH3
Ph
meso Diastereomer
One -CH3 at 1.6 ppm and one at 1.8 ppm
Methine protons at 4.75 ppm
(±)-Diastereomer
Single -CH3 peak at 1.7 ppm
Methine protons at 5.52 ppm
PROJECT 14: SUGARS: GLUCOSE PENTAACETATES
QUESTIONS: What is the relative stability of - and -D-glucose pentaacetate?
How can you distinguish between kinetic and equilibrium control
in the synthesis of the glucose pentaacetates?
PROJECT 14.1 Synthesis of - and -D-Glucose Pentaacetate
PROJECT 14: SUGARS: GLUCOSE PENTAACETATES
PROJECT 14.2 Investigation of Kinetic and Equilibrium Control in the
Glucose Pentaacetate System
• PRELABORATORY ASSIGNMENT: Analyze NMR spectra of both crude
and recrystallized - and -D-glucose pentaacetates.
• C-1 (anomeric) protons: - glucose, 6.33 ppm; - glucose, 5.72 ppm.
• Determine ratio of - and -D-glucose pentaacetate in each sample.
• Are the recrystallized samples at least 95% pure?
• Design a set of experiments to investigate the equilibration of - and
-D-glucose pentaacetates.
• Students are given two isomerization methods to use for the tests.
• NMR analysis of all products.
PROJECT 14: SUGARS: GLUCOSE PENTAACETATES
PROJECT 14.3 Computational Chemistry Experiment
• In aq. solutions of -glucose anomer, the C-1 hydroxyl group is equatorial
and with the-glucose anomer, the C-1 hydroxyl group is axial.
• Build models of axial- and equatorial-isomers of:
O
C
CH3
O
C
O
Cyclohexyl acetate
O
CH3
O
2-Acetoxytetrahydropyran
• Calculate heats of formation for each isomer.
• Use difference in heats of formation for the 2-acetoxytetrapyran conformers
to calculate Keq for - and -D-glucose pentaacetate.
• Are your calculations consistent with your investigations of kinetic and
equilibrium control in the glucose pentaacetate system?
ACKNOWLEDGEMENTS
•
Paul F. Schatz, University of Wisconsin
•
Colleagues and students at Vassar and Carleton
•
Jhong Kim, UC Irvine
•
My many Vassar student assistants
•
W. H. Freeman and Co, publishers
PROJECT 9: BROMINATION OF
CYCLOHEX-4-ENE-cis-1,2-DICARBOXYLIC ACID
QUESTION: What is the stereochemistry of bromine addition to the double bond?
• A three-step synthesis project.
• First step: Diels-Alder synthesis and subsequent hydrolysis of anhydride.
• Pyridinium tribromide is the source of Br2.
H
N+ Br3-
O
H
O
H
Br
OH
OH
OH
acetic acid
OH
Br
H
H
O
O
• Dimethyl ester is subsequently prepared and stereochemistry determined by NMR.
PROJECT 9: BROMINATION OF
CYCLOHEX-4-ENE-cis-1,2-DICARBOXYLIC ACID
anti Addition of Bromine: Bromonium ion pathway.
Br
Br
CO2CH3
Methyl peaks appear ~3.7 ppm.
Two singlets having equal integration.
CO2CH3
syn Addition of Bromine: Carbocation pathway.
Br
CO2CH3
Br
CO2CH3
Br
CO2CH3
Br
CO2CH3
Plane of symmetry
Diastereomers
Several possible outcomes for synthesis :
• Two methyl singlets ~3.7 with relative areas unequal.
• One methyl peak at ~3.7 if one diastereomer forms much faster.
• Both syn and anti addition occur: Complex pattern of 4 different methyl peaks
at ~ 3.7 ppm with different integrations.
TUESDAY LAB
GREEN CHEMISTRY: SYNTHESIS AND HYROGENATION
OF SUBSTITUTED CHALCONES A GUIDED-INQUIRY PROJECT
QUESTION: Which functional groups are reduced in the hydrogenation
of a polyfunctional molecule?
Part 1
Synthesis of the Chalcone
H
NaOH
+
R2
R1
R1 = CH3, OCH3, or Cl
•
O
O
O
H2O
R2 = CH3 or OCH3
Use concentrated aqueous NaOH solution for reaction.
• Product recrystallized from 95% ethanol.
•
R2
R1
Product analyzed by IR and NMR.
Reference: Palleros, D. R. J. Chem. Educ. 2004, 81, 1345–1347.
Disubstituted Chalcone
GREEN CHEMISTRY: SYNTHESIS AND HYROGENATION
OF SUBSTITUTED CHALCONES A GUIDED-INQUIRY PROJECT
Part 2
Hydrogenation of the Chalcone
O
Pd/C
NH4CHO
Hydrogenation Product(s)
methanol
R1
R2
• Determine a suitable TLC solvent for the chalcone.
• Completion of reaction determined by TLC analysis.
• Product analyzed by TLC, IR, NMR, and GC-MS.