Experiment 20
NaBH4
Reduction of p-Vanillin
O
HO
H
CH2
C
+
1. NaBH4
2. H3O+ workup
OCH3
OCH3
OH
4-hydroxy-3-methoxybenzaldehyde
(p-vanillin)
OH
4-hydroxy-3-methoxybenzyl alcohol
(vanillyl alcohol)
Objectives:




To synthesize vanillyl alcohol by reduction
using NaBH4.
To isolate and purify the product by
vacuum filtration.
To analyze the purity of products using
TLC, HPLC and melting point analysis.
To characterize the reactants and
products using 1H-NMR and IR
spectroscopy.
Before coming to lab…

Review these techniques:

Vacuum filtration

TLC Analysis

HPLC analysis

Melting point analysis
CHEMICAL EQUATION
This is provided as a
solution. Be sure you
understand how to
calculate theoretical yield!
O
HO
H
CH2
C
+
1. NaBH4
2. H3O+ workup
OCH3
OCH3
OH
4-hydroxy-3-methoxybenzaldehyde
(p-vanillin)
OH
4-hydroxy-3-methoxybenzyl alcohol
(vanillyl alcohol)
MECHANISM
O
H
C
O
H
H
B
H
H
C
HO
H
CH2
H
O
H
H
H
+ H2O + B(OH)3
(from 6M HCl)
OH
4-hydroxy-3-methoxybenzaldehyde
(p-vanillin)
OCH3
OCH3
OCH3
OH
OH
4-hydroxy-3-methoxybenzyl alcohol
(vanillyl alcohol)
REDUCING AGENTS



Reducing agents cause a reaction resulting in a product
containing more bonds from carbon to hydrogen (or
fewer bonds to oxygen).
NaBH4 (sodium borohydride) is a versatile and useful
reducing agent in organic chemistry, however will only
reduce carbonyl groups of aldehydes and ketones.
LAH (lithium aluminum hydride) is another common
reducing agent, however use of this reducing agent will
result in the reduction of many other carbonyl
containing compounds, including esters, carboxylic acids
H
H
Li+
Na+
and amides.
H
B
H
H
Sodium
borohydride
H
Al
H
H
Lithium
aluminum
hydride
H
Hydride
ion
TLC STAIN—2,4-DNP
R
H
C
HN
NH 2
HN
O
NO2
N
NO2
+
H
R
aldehyde or ketone
NO2
2,4-DNP
(red-orange)
NO2
product hydrazone
(yellow-orange)
2,4-DNP is a TLC stain used to detect
aldehydes and ketones
OVERVIEW







Dissolve p-vanillin in ethanol.
Add NaBH4 solution drop-wise via addition
funnel while stirring.
Add 6M HCl to hydrolyze intermediate,
forming alcohol product.
Isolate solid product by vacuum filtration.
Prepare TLC and HPLC samples—submit HPLC
sample for analysis.
Perform TLC experiment on product, staining
with 2,4-DNP stain.
Secure product and allow to dry until next lab
period.
OVERVIEW
AT THE BEGINNING OF THE NEXT LAB PERIOD…

Obtain final mass of product and calculate %
yield.

Perform melting point analysis.

Analyze HPLC results.
SYNTHESIS




Mix p-vanillin and ethanol in a
water cooled 25 mL flask with
stir bar until dissolved.
Set up apparatus shown. Add
NaBH4/NaOH solution to
separatory funnel.
Add a few ice cubes to the
water bath.
Begin adding NaBH4/NaOH
solution SLOWLY.
7
8
6 5
4
3
2
9
1
0
1
7
8
9
6 5
11
4
3
2
1
SYNTHESIS



Remove water bath. Stir 5
min.
Return ice water bath. Add
6M HCl until pH = 6.
Stir for 10 min. in ice bath.
PRODUCT ISOLATION &
PURIFICATION



Suction filter to isolate solid.
Rinse solid in funnel with icecold water.
Dry solid under vacuum for a
few minutes.
PRODUCT ANALYSIS




Prepare TLC and HPLC sample of solid
product.
Secure remaining product and submit
to instructor to dry until next lab
period.
filter paper
Submit HPLC sample for analysis.
Prepare TLC plate using sample and
provided standards.

Develop plate and visualize under UV.

Stain plate with 2,4-DNP TLC stain.
A
B
C
PRODUCT ANALYSIS—TLC

TLC Analysis
 Used to identify and determine purity of
products at the end of the experiment.
 2,4-DNP will be used as a stain to detect the
presence/absence of the aldehyde functional
group.
Table 20.1
Rf values
should always
be recorded to
2 decimal
places! Never
more, never
less!
Compound
p-vanillin
Vanillyl Alcohol
Standard
Rf
Sample
Rf
TLC
Diagram
Sketch the plate
as much to scale
as possible!
Include cm
measurements
for all spots and
solvent front!
PRODUCT ANALYSIS—IR

IR Analysis
 IR spectra of reactants and products can be
used to determine the presence and absence
of certain types of functional groups which
indicate the conversion of one compound to
another during the course of the synthesis.
Table 20.2
Functional Group
OH stretch
C-O stretch
C=O stretch
Base
Values
p-vanillin
Vanillyl alcohol
Frequency
(cm-1)
Frequency
(cm-1)
Frequency
(cm-1)
3200-3600
1000-1300
1680-1740
Notice that
the product
should have
2 entries for
O-H and C-O!
PRODUCT ANALYSIS—NMR

NMR Analysis
 1H-NMR spectra of reactants and products can
be used to determine the presence and
absence of certain types of signals which
indicate the conversion of one compound to
another during the course of the synthesis.
O
This is
where the
major
change is!
H1
C
6
2
HO
7
CH2
1
6
2
5
5
OCH3
OCH3
3
3
OH
4
OH
4
Tables 20.4 and 20.5
Table 20.4
Theoretical yield (g)
Actual yield (g)
Percent yield
Product Appearance
Experimental Melting Point (oC)
Table 20.5
Atom Economy (%)
Experimental Atom Economy (%)
“Eproduct”
Cost per synthesis ($)
Cost per gram ($/g)
PRODUCT ANALYSIS—HPLC

HPLC Analysis
 Used at the end of the experiment to
identify and quantify compounds present
during the synthesis, as well as the purity
of the final products from each step.
Table 20.6
Compound
p-vanillin
Vanillyl alcohol
HPLC Retention Times
(min)
Standard
Sample
PRODUCT ANALYSIS—HPLC

HPLC Analysis
 Used at the end of the experiment to
identify and quantify compounds present
during the synthesis, as well as the purity
of the final products from each step.
Compound
p-vanillin
Vanillyl alcohol
HPLC Retention Times
(min)
Standard
Sample
SAFETY CONCERNS



Ethanol, ethyl acetate, hexane, and
acetone are all FLAMMABLE materials.
Sodium borohydride and 2,4-DNP are
TOXIC in large concentrations.
Sulfuric acid, used to prepare 2,4-DNP
stain, is CORROSIVE.
WASTE MANAGEMENT
o LIQUID WASTE : Place all liquid waste into this
container including filtrates and aqueous washes
from extraction.
o GLASS WASTE: Place used TLC and melting point
capillary tubes in this container.
o PAPER WASTE: Place any gloves, TLC plates,
filter papers, paper towels, etc. in the yellow
trashcan.
CLEANING


Any glassware used to contain only volatile
organic solvents can simply be rinsed with
wash acetone.
All other glassware should be cleaned with
soap, water and brush, then rinsed with
wash acetone or hand dried.
LABORATORY NOTEBOOK
(Pre-lab)
• OBJECTIVE
(Must clearly state…)
• What compounds will be made and how
• What will be investigated with the compounds
• CHEMICAL EQUATION
• Include the general chemical equation from the top of page 169 from hondout.
• TABLE OF PHYSICAL DATA
(Complete the following table using MSDS
sheets from http://hazard.com/msds or www.chemexper.com ONLY. Wikipedia is
unacceptable.)
Compound
p-vanillin
Sodium borohydride
ethanol
Sodium hydroxide
Vanillyl alcohol
Hydrochloric acid
Ethyl acetate
Hexane
2,4-dinitrophenylhydrazine
MW (g/mol) bp(oC) mp (oC)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
• REFERENCE TO PROCEDURE
d (g/mL)
X
X
X
X
X
X
(Must include…)
• full title including edition and author names
• numbers where actual procedure can be found
OSHA HAZARDS
LABORATORY NOTEBOOK
(In-lab)

•
DATA/CALCULATIONS

Initial mass of p-vanillin used

Volume of NaBH4 solution used

Volumes of ethanol and 6M HCl used

Weights of small filter paper, filter + product, and final product mass

HPLC vial slot #

TLC diagram, including all cm measurements

Example Rf calculation

Theoretical yield calculation (not just value!)

% yield calculation (not just value!)

Atom economy calculation (not just value!)

Experimental atom economy calculation (not just value!)

“Eproduct” calculation (not just value!)

Cost per synthesis calculation (not just value!)

Cost per gram calculation (not just value!)

Cost per synthesis calculation

Cost per gram calculation
EXPERIMENTAL PROCEDURE
•
In paragraph form, describe the procedure that you actually followed during the lab.
•
Paragraph must be written in PAST TENSE, PASSIVE VOICE.
•
Include any volumes or weights of chemicals used during the experiment.
•
Include any mistakes, accidents or observations if applicable.