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 BF4Cl HBF4 CuCl CuBr + N N KI H3O+ , D NaNO2, HCl 0C CuCN NH2 H3PO2 H OH I Br D F

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.
NaNO2 + HCl Sodium Nitrite H3O+ + HONO H C6H5N Primary aromatic amine C6H5 N N OH H+ C6H5 N N H HONO + Na+ ClNitrous Acid + H2O + H2ONO H + C6H5N N O H + N=O

2H2O + - H+

+ N O

C6H5N N O H + C6H5 N N

- H2O + OH2

+ C6H5 N N

Diazonium ion

The diazonium ion is reasonably stable in aqueous solution at 0C; 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 Benzenediazonium chloride + N CH3 CH3 N,N-Dimethylaniline a diazo dye (orange colored) N N N CH3 CH3

Diazonium salts are not ordinarily isolated because the dry solid is explosive.

Synthesis of 2-lodobenzoic Acid

O OH NH2 O OH NH3+ Cl+ HCl + NaNO2 + HCl + Na+ Cl+ 2 H2O O OH N N KI O OH I + N2 + K+ Cl2-Iodobenzoic acid MW 248.02 mp 126-163C

2-Aminobenzoic acid MW 137.14, mp 144-148C

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 5C, 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 40C, a vigorous reaction ensues (gas evolution and separation of a tan solid). After reacting for 10 min, the mixture is heated to ~90C 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 164C); 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 30C instead of 0 to 5C? 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 Missed

Date, Name, Desk #, Experiment # & Title(abbreviated after 1st pg), Section & TA Name SummaryGoals- Reaction schemes esp. for synthesis, mechanisms and techniques Reactions, structures, conditions, diagrams (3-5 pts each) Completeness of Chemical Data Table(s) PreLab Exercise Chromatographic Behavior Comparison Spectral Features Comparison Work-up purification and isolation TOTAL FOR PRELAB Date Handed in: General Comments:

4 10 12 14 8 16 12 12 12 100

Total Points:

Synthetic Experiment Final Report Grading Sheet

Name: TA: Date:

Final Report For Exp't #:30 Title The Sandmeyer Reaction: 2-Iodobenzoic Acid
Possible Points Missed Points

Name, Date, Experiment Title (abbreviated after 1st page) and every page numbered OBSERVATION and DATA - Overall organization, readability, completeness Data: Weighing data, molecular weights, moles, d, v of all necessary compounds. Yield: Show % yield, weight and limiting reagent. 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) Product Analysis Data: Quality and Interpretation Structure(s) drawn on each Spectrum or Chromatogram mp and TLC Assignment and discussion of all TLC spots

4 8 12 12

8 16

24

POSTLAB QUESTIONS. TOTAL POINTS Date Handed in: General Comments:

16 100

Total Points: