EXPERIMENT 3 (Organic Chemistry II) Pahlavan/Cherif Nitration of Aromatic Compounds: Preparation of methyl-m-nitrobenzoate
a) Study electrophilic aromatic substitution reaction (EAS)
b) Study regioselectivity for EAS reactions
150 – mL beaker
Methyl benzoate 400-mL beaker
Sulfuric acid (conc.) 125-mL flask
Nitric acid (conc.) Stirring rod
Methanol Suction filtration funnel
Unlike nucleophilic substitutions, which proceed via several different mechanisms, electrophilic aromatic
substitutions (EAS) generally occur via the same process. Because of the high electron density of the
aromatic ring, during EAS reactions electrophiles are attracted to the ring's π system and protons serve as
the leaving groups.
Equation 1. During S reactions, however, nucleophiles attack an aliphatic carbon and weak Lewis bases N1
serve as leaving groups.
++Ar - HEAr - EEq. 1++H
Generally, EAS reactions occur in three steps, Scheme I. During Step I, the electrophile is produced,
Usually, by the interaction of a compound containing the potential electrophile and a catalyst. During Step II, the aromatic π system donates an electron pair to the electrophile, forming a σ bond ( an arenium -) affording the substituted cation) followed by deprotonation in step III in the present of a base ( HSO4
arene. EAS reactions are generally second-order processes, i.e., first order in electrophile and first order in arene. Thus, Step II. is the rate-determining step (rds); rate = k [arene][electrophile]. 2
Electrophilic Aromatic Substitution: Nitration of Methyl Benzoate
Benzene rings are components of many important natural products and other useful organic compounds. Therefore, the ability to put substituents on a benzene ring, at specific positions relative to each other, is a very important factor in synthesizing many organic compounds. The two main reaction types used for this are both substitutions: Electrophilic Aromatic Substitution (EAS) and Nucleophilic Aromatic Substitution (NAS). The benzene ring itself is electron-rich, which makes NAS difficult, unless there are a number of strongly electron-withdrawing substituents on the ring. EAS, on the other hand, is a very useful method for putting many different substituents on a benzene ring, even if there are other substituents already present. Electrophilic Aromatic Substitution chapter describes the factors involved in the regioselectivity for EAS reactions using benzene rings, which already have substituents on them.
In this experiment you will put a nitro (—NO) group on a benzene ring, which already has an ester group, 2+attached to it (methyl benzoate). The actual electrophile in the reaction is the nitronium ion (NO), which 2
is generated in situ ("in the reaction mixture" HNO/HSO) using concentrated nitric acid and 324
concentrated sulfuric acid.
Methyl Benzoate Methyl m-nitrobenzoate
MW = 136.15 g/mol MW = 181.14 g/mol o Density = 1.094 m/ml B.P. = 279 C oo B.P. = 198-199 C M.P. = 78-80 C o M.P. = -12 C
CH) directs the aromatic substitution reaction to the position that are The carbomethoxy group (-CO23
meta to it. As a result the m-nitrobenzoate is the principal product from this reaction. Formation of dinitro products from this reaction is unlikely under the conditions in which you carry out your reaction. The reason for this is that both carbomethoxy groups as well as the nitro group (on the mono nitrated product) are deactivating groups making the second nitration less favorable.
Concentrated sulfuric acid is the solvent for this reaction and is involved in the formation of nitronium ion +(NO) from concentrated nitric acid. Water has a retarding effect on the nitration since it interferes with 2+the nitric acid-sulfuric acid equilibrium (shown below) that generates the required nitronium ion (NO). 2
+ -HONO + HSOHONO + HSO224224
+ -SOHO+HHO242+ HSO34
+-HO-NO + H - HSONO +HSO HO24+242
Temperature also has an effect on the product distribution from this reaction. Higher the temperature, greater will be the amounts of dinitration products formed from this reaction.
Caution: Avoid contact with the acids used in this experiment and the reaction product. Prevent contact with the skin, eyes, and clothing; work in the hood. An acid spill is neutralized using solid sodium carbonate or bicarbonate. The reaction is highly
exothermic. A vigorous reaction will occur if the acid mixture is added too rapidly to the methyl benzoate.
Concentrated nitric acid and concentrated sulfuric acid are both strong oxidizers, and
strongly corrosive--wear gloves while handling them, and avoid breathing their vapors. Methyl benzoate and methyl m-nitrobenzoate are irritants -- wear gloves while handling
them. Methanol is a flammable liquid, and is toxic -- no flames will be allowed in lab,
wear gloves while handling it, and avoid breathing its vapors.
In a 125-ml. Erlenmeyer flask mix 1.5 ml. of methyl benzoate and approximately 4.0 ml. of concentrated sulfuric acid (drop-wise), and chill it in an ice bath. Continue to cool the mixture in the ice bath to reduce the heat, which produced in the reaction. After complete addition of sulfuric acid, add approximately 2.0 ml concentrated nitric acid (measured in 10- ml graduated cylinder) drop- wise using a small graduated plastic pipette and mix by gentle swirling. Continue to cool the reaction mixture. Allow the reaction mixture to stand at room temperature for about five minutes.
Float the 125-ml flask in a 400-ml beaker hot water bath. Remove the flask occasionally and swirl the content carefully. After fifteen minutes heating pour the reaction mixture in 100-ml of ice water contained in a 150- ml beaker, with stirring.
Isolate the product by vacuum filtration, wash the product with (ice) cold water (20 mL) followed by cold methanol (10 mL).
Proper washing removes the more soluble ortho isomer.The crude material may be purified by
recrystallization from a small volume ( ~ 10 ml) of hot methanol (optional). The crude product is pressed dry. You may need to air dry (or hand dry using paper towels) the product. Discard the aqueous filtrate down the drain with lots of water.
oDetermine the weight, melting point, and percentage yield. Pure methyl m-nitrobenzoate melts at 78.5C.
Submit the product to your instructor in a paper wrapped and labeled including your name(s).
EXPERIMENT 3 (Organic Chemistry II)
Nitration of Aromatic Compounds: Preparation of methyl-m-nitrobenzene
REPORT FORM Name _______________________________
(please show your calculations on results of laboratory report)
1. Weight of methyl benzoate ________ g ________ moles
2. Theoretical yield of methyl m-nitrobenzoate ________ g ________ moles
3. Weight of methyl m-nitrobenzoate ________ g ________ moles
4. Percentage yield of methyl m-nitrobenzoate ________ %
05. Melting point range of product _____________ C
06. Literature melting point of methyl m-nitrobenzoate _____________ C
Pre-Laboratory Questions–EXP 3 Name:
Due before lab begins. Answer in space provided.
1. Which is nitrated faster? toluene or nitrobenzene? Explain.
2. Why is methyl m-nitrobenzoate formed in this reaction instead?
of o- and p-? Indicate the product formed on (mono) nitration of each of the folowing
a) Cyanobenzene (benzonitrile) b) toluene c) benzoic acid.
3. What product would you expect if methyl benzoate underwent dinitration?
4. Methyl-m-nitrobenzoate is an excellent (identification) derivative of methyl benzoate. What
are the properties of methyl-m-nitrobenzoate that makes it an excellent derivative of the
starting ester? .
5. List three combinations of reagents used for nitration of aromatic compounds?
Post-Laboratory Questions–EXP 3 Name:
Due after completing the lab.
1. Why is concentrated sulfuric acid employed in this reaction? What is the electrophile that is produced
by the reaction of sulfuric acid and nitric acid/
2. Why is it important to maintain the reaction temperature low and the addition of
nitric acid-sulfuric acid mixture carried out slowly?
3. Explain why concentrated HSO, not concentrated HCl, was used in this experiment? 24
4. Which ring of phenyl benzoate would you expect to undergo nitration more easily? Explain.
5. Which is nitrated faster, toluene or phenol? Explain.