Chemistry 243 Lab
Electrophilic Aromatic Iodination of Vanillin
Introduction:
Substitution on an aromatic ring is a two step process called Electrophilic
Aromatic Substitution (EAS). The first step is addition across a pi bond in the aromatic
ring resulting in a resonance stabilized carbocation intermediate. The second step is
elimination of the extra hydrogen to regain the aromatic structure. This mechanism
allows us to predict regioselectivity (o,p director or m director) and relative reactivity
(activating or deactivating) based upon whether substituents already on the ring are
electron donating or electron withdrawing.
Halogenation of the benzene ring is typically carried out with elemental halogen
(Br2, Cl2, I2) and a metal catalyst. Although iodine is relatively harmless, bromine is a
volatile liquid which can cause serious burns to the eyes and skin in both gas and liquid
form as well as potentially severe to fatal respiratory irritation. Chlorine is a gas at room
temperature (bp = -34C) that can also cause serious and even fatal respiratory problems.
Clearly, bromine and chlorine should not see much use in the undergraduate laboratory.
However, the EAS mechanism in general and halogenation in particular are important
tools of the organic synthetic chemist.
As mentioned in chapter 15, iodine has a relatively low reactivity towards EAS.
As a result, powerful oxidizing agents (nitric acid, et al) are frequently used to effect this
reaction. If the aromatic structure contains several strong electron donating groups, then
the addition is easier, can be difficult to control the regioselectivity and sometimes
polyiodination is achieved.
In this experiment, you will use sodium iodide as your source of iodine and
common bleach (sodium hypochlorite: NaOCl) as an oxidizing agent. The solvent will
be aqueous alcohol. The green benefits of this method include milder oxidizers (bleach
instead of nitric acid) and more environmentally friendly solvents (water and alcohol
instead of halogenated liquids).
I.
Table of Reagents and Products
name of
m.w.
mL
density
compound
used
(g/mL)
vanillin
152.15
NaI
149.9
NaOCl
(5.25%)
74.4
product
278.05
Limiting reagent
-
grams
used
moles
used
ratio of moles
theory
used
1.078
-
-
-
________________________________________________
O
O
I
NaI
OH
OMe
NaOCl
OH
OMe
Safety Precautions: Sodium hypochlorite is household bleach. It may bleach or
otherwise damage your clothing/hair/skin. Methanol and ethanol are flammable.
Procedure:
Reaction:
1. In a 100 mL round bottom flask containing a magnetic stir bar, dissolve 1.0 g of
vanillin in 20 mL of ethanol. Add 1.17 g of NaI, then cool to 0 C with ice water
bath.
2. Use a separatory funnel to add 11 mL of aqueous sodium hypochlorite solution
(5.25% w/w) dropwise to the stirred reaction mixture of a period of 10 minutes.
The color should change from pale yellow to red-brown.
3. After the addition is complete, allow mixture to warm to room temperature and
continue stirring another 10 minutes.
Workup and Isolation:
4. Add 10 mL of sodium thiosulfate (10% w/w), then acidify with 10% HCl. Use
litmus paper to monitor pH. 6 mL is typically required. At this point, your
compound should precipitate out of solution.
5. Remove the ethanol from the suspension by letting it evaporate overnight. Water
should still be present.
6. Cool the flask in an ice bath for ten minutes, then collect the precipitate by
vacuum filtration. Wash well with ice cold water, then a small amount (a few mL
at most) of cold ethanol. Continue to draw air through the crude product to help
dry it for several minutes. Record the mass of the crude product.
7. Recrystallize your crude product using a solvent mixture of isopropyl alcohol and
water. Do this by dissolving your product in barely enough 2-propanol to do the
job in a 100 mL Erlenmeyer flask. While continuing to heat it. Add enough hot
water to make the mixture become cloudy, then more hot isopropanol to generate
a clear (though colored) solution.
8. Remove the flask from the heat, allow to cool to room temperature, then place in
an ice bath for a few minutes to maximize crystal recovery.
9. Collect by vacuum filtration again drawing air through the product for a few
minutes to facilitate drying.
Characterization
10. Take the mass and mp of your product (literature value = 183-185C).
Questions
1. What are the products of these reactions?
Br2
FeBr3
NBS, heat
HOOH
O
CH3CH2Cl
AlCl3
NO2
NaOCH3
heat
Br
C(CH3)3
+
O
CH3CH2CCl
C(CH3)3
HNO3
H2SO4
1. AlCl3
2. H2O
2. Design a synthesis for each of the following using benzene or toluene as your
only aromatic source. Show all intermediates and reagents for each step.
Cl
NO2
NH3
NO2
OCH3
CH2Br
Br