Exp't 30
The Sandmeyer Reaction: 2-lodobenzoic Acid
from K. L. Williamson, Macroscale and Microscale Organic Experiments, 2nd Ed. 1994, Houghton Mifflin, Boston p 558, Revised 10/31/98
Prelab Exercise: Outline the steps necessary to prepare 4-bromotoluene, 4-iodotoluene, and 4-fluorotoluene from benzene.
Introduction:
The Sandmeyer reaction is a versatile means of replacing the amine group of a primary aromatic amine with a number of
different substituents:
+
N N BF4-
D
F
Cl
HBF4
CuCl
Br
CuBr
+
N N
KI
I
H3O+ , D
OH
H3PO2
NaNO2, HCl
0°C
CuCN
H
NH2
C N
Scheme I
The diazonium salt is formed by the reaction of nitrous acid with the amine in acid solution. Nitrous acid is not stable and
must be prepared in situ; in strong acid it dissociates to form nitroso ions, +NO, which attack the nitrogen of the amine. The
intermediate so formed loses a proton, rearranges, and finally loses water to form the resonance-stabilized diazonium ion.
HONO + Na+ ClNitrous
Acid
NaNO2 + HCl
Sodium
Nitrite
+
H2O + H2ONO
H3O+ + HONO
H
C6H5N
+
N O
H
H
+
C6H5N N O
- H+
H+
C6H5 N N
- H2O
+
OH2
+
N=O
C6H5N N O
H
Primary
aromatic amine
C6H5 N N OH
2H2O +
H
+
C6H5 N N
C6H5 N N
+
Diazonium ion
The diazonium ion is reasonably stable in aqueous solution at 0°C; on warming up it will form the phenol, as seen in
Scheme I. A versatile functional group, it will undergo all the reactions depicted there as well as couple to aromatic rings
activated with substituents such as amino and hydroxyl groups to form the huge class of azo dyes (see Exp't 31).
Cl+
N N
+
N
CH3
N N
CH3
Benzenediazonium
chloride
N,N-Dimethylaniline
N
CH3
CH3
a diazo dye
(orange colored)
Diazonium salts are not ordinarily isolated because the dry solid is explosive.
Synthesis of 2-lodobenzoic Acid
O
OH
NH2
O
OH
O
OH
NH3+ Cl+ HCl
N N
+ NaNO2 + HCl
KI
OH
I
+ N2
+ K+ Cl-
+ Na+ Cl-
2-Aminobenzoic acid
MW 137.14, mp 144-148°C
O
+ 2 H2O
2-Iodobenzoic acid
MW 248.02
mp 126-163°C
A 250-mL round-bottomed flask containing 6.9 g of anthranilic acid, 50 mL of water, and 12 mL of concentrated hydrochloric
acid is heated until the solid is dissolved. The mixture is then cooled in ice. When the temperature reaches 0 to 5°C, a
solution of 3.6 g of sodium nitrite (NaNO2) in 25 mL of water is added slowly. After 5 min, a solution of 8.5 g of potassium
iodide in 12 mL of water is added, (whereupon, a brown complex partially separates). The mixture is let stand without cooling
for 5 min and then carefully warmed on a bowl of lukewarm water maintained at ~ 45 °C on a hot plate with occasional
swirling. When the reaction reaches about 40°C, a vigorous reaction ensues (gas evolution and separation of a tan solid).
After reacting for 10 min, the mixture is heated to ~90°C for 10 min on the hot plate and then cooled in ice.
Isolation and Purification:
A pinch of sodium bisulfite is added to destroy any iodine present, and the granular dark tan to brown product is collected and
washed with water. The still-moist product is dissolved in 35 mL of 95% ethanol, and the brown solution is decolorized with
Norit pellets and then diluted with 15 mL of hot water. The solution is brought to the boiling point, filtered hot, diluted with
15 to 20 mL of cold water, and let stand. 2-lodobenzoic acid separates in large, slightly yellow needles (mp 164°C); even if
fairly brown crystals are obtained, it is still possible to get a good mp; yield is approximately 8.3g (71%).
Cleaning Up The reaction mixture filtrate and mother liquor from the crystallization are combined, neutralized with solid
sodium carbonate, and flushed down the drain with a large excess of water. Norit is placed in the solid waste bin.
Questions
1. Nitric acid is generated by the action of sulfuric acid on sodium nitrate. Nitrous acid is prepared by the action of
hydrochloric acid on sodium nitrite. Why is nitrous acid prepared in situ, rather than obtained from the reagent shelf? Hint:
What is the brown gas evolved during the acidification of sodium nitrite? Refer to a freshman text like Brown and Lemay for
information on nitrous acid.
2. What by-product would be obtained in high yield if the diazotization of p-toluidine were carried out at 30°C instead of 0 to
5°C?
3.
How would 4-bromoaniline be prepared from acetanilide?
O
H3C
NH
acetanilide
Exp't 30
Synthetic Experiment PreLab Grading Sheet
Name(s):
TA:
Date:
PreLab For Exp't #:30
Title: The Sandmeyer Reaction: 2-Iodobenzoic Acid
Possible
Points
Points
Date, Name, Desk #, Experiment # & Title(abbreviated after 1st pg), Section &
TA Name
4
Summary-
10
Goals- Reaction schemes esp. for synthesis, mechanisms and techniques
12
Reactions, structures, conditions, diagrams (3-5 pts each)
14
Completeness of Chemical Data Table(s)
8
PreLab Exercise
16
Chromatographic Behavior Comparison
12
Spectral Features Comparison
12
Work-up purification and isolation
12
TOTAL FOR PRELAB
100
Date Handed in:
General Comments:
Total Points:
Missed
Synthetic Experiment Final Report Grading Sheet
Name:
TA:
Date:
Final Report For Exp't #:30
Title The Sandmeyer Reaction: 2-Iodobenzoic Acid
Possible
Points
Name, Date, Experiment Title (abbreviated after 1st page) and every page
numbered
4
OBSERVATION and DATA - Overall organization, readability, completeness
8
Data: Weighing data, molecular weights, moles, d, v of all necessary
compounds.
12
Yield: Show % yield, weight and limiting reagent.
12
Missed
Points
Purity: Give melting point other signs of purity.
RESULTS AND DISCUSSION - Overall organization, readability, completeness
Results; Achievement of goals (8 pts results/ 8 pts goals)
8
16
Product Analysis Data: Quality and Interpretation – Structure(s) drawn on
each Spectrum or Chromatogram
24
mp and TLC
Assignment and discussion of all TLC spots
POSTLAB QUESTIONS.
16
TOTAL POINTS
100
Date Handed in:
General Comments:
Total Points: