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Exp’t 32

Synthesis of Methyl Salicylate: Amine Diazotization
Adapted by R. Minard and K. Smereczniak (Penn State Univ.) from M. Zanger and J. R. McKee's,"The Synthesis of Methyl Salicylate: Amine Diazotization," J. Chem. Ed., 65 12,1106 (1988). Revised 10/9/00

Introduction: The synthesis of methyl salicylate is a safe and effective way to observe an amine diazotization. It also includes pleasant smells due to chemicals that are used for artificial flavorings. The synthesis uses diazonium salts to replace the amine group of an aromatic amine with a hydroxyl group. The reaction proceeds as follows: H2SO4 + 2 NaNO2 Na2SO4 + 2 HNO2 NO+ + H2O + Na2SO4

(1)

H2SO4 NaNO2

methyl anthranilate

methyl salicylate

(2)

The mechanism for the formation of the diazonium ion is as follows:
O H3C O C NH2
+

O H3C O C N O

H
+N

N O

-H+

O H3C O C N N O H 5

H 1 4

O H3C O C N N OH H
+

O H3C O C N N OH2

-H2O

O H3C O C N N

O H3C O C

N N+

6

7

2

Prelaboratory Exercises: 1. In your chromatographic behavior comparison PreLab section, be sure to include the triazene product described below. 2. Draw the Lewis structures for the nitrite ion (NO2-), the nitroso group (R-N=O), and the diazonium group (R-N≡N+). If there are resonance forms possible, show these too. Cautions: Sodium nitrite is toxic. Handle with care! DO NOT allow the benzenediazonium sulfate solution to warm up or it will decompose leading to undesirable side-products. Concentrated H2SO4 is very corrosive. Handle with care and do not spill it on anything. TLC

Extract the aqueous phase with three 5-mL-portions of dichloromethane. put 11 mL of distilled water and a 1-inch magnetic stirring bar. bring the solution to a boil on a sand bath. allow the reaction to cool back down to about 4°C before adding more of the nitrite solution. A reddish oil that smells of wintergreen should form.3 mL of distilled water and 1. While this solution is cooling to 2-5°C. Monitor the reaction temperature with a thermometer and if the temperature rises.You are required to run a TLC to monitor the progress of the reaction. don’t take more than you need). mark each band and calculate the Rf . and dry this dichloromethane solution of your product over anhydrous sodium sulfate. While stirring magnetically. make up a solution of 2. Synthesis: In a 50-mL Erlenmeyer flask. place a heavy band of your product mixture on the origin line by continously applying overlapping spots. For both plates. Dropwise. slowly add 3 g of concentrated sulfuric acid (approximately 1. H2SO4 bottle with a glass Pasteur pipet into a graduated cylinder. Put the flask into a beaker of ice bath and add 9 to 12 g of ice directly to the flask. while the desired product (methyl salicylate) has the distinct odor of wintergreen. there will be two visible spots (yellow and brown) and one additional spot brightly visible under the UV lamp. Isolation and Purification: Allow the reaction to cool to room temperature and then pour into a 125-mL-separatory funnel. Analysis of the product will be through TLC. Plates should have three spots (or lanes) on the origin: one for the main organic starting material that is being transformed. Continue to stir for 15 minutes.5 mL. and boil for 5 to 10 minutes. bring the plate under your nose and gently smell along the plate. spot a diluted (1 drop per mL) dichloromethane solution of the starting material (methyl anthranilate) next to the dichloromethane solution of your product. Starting at one end of the plate. Methyl anthranilate has a grape odor. Add 4 crystals of urea to decompose any excess nitrous acid.2 g of sodium nitrite in a reaction tube. The precipitate should eventually disappear. and then add 2. Using your olofactory detector. The band should have at least a 1/8” margin on each side.25% ethyl acetate solution. After developing in the hexane / ethylacetate solution.0 g of methyl anthranilate. allow the mobile phase to evaporate. Remove the stir bar and add a boiling stick. one for a cospot (starting material and the reaction mixture). On one TLC plate. measure the exact amount you need by transfering from the conc. combine the dichloromethane extracts. 1 cm Product "band" After developing. The lowest (yellow) spot is the triazene formed from the diazonium salt reacting with the starting material as follows: O CH 3OC H N: H +N O COCH 3 N CH 3OC O H N N N O COCH 3 + Determine the identity of the remaining two spots by TLC combined with a special olfactory detector--YOUR NOSE! Instead of a single dot. as shown below. and one for the reaction mixture. Continue to stir! A precipitate will form. Make sure to keep the mixture below 10°C at all times. Prepare about 10 mL of a 75% hexane . add 23 drops of this solution very slowly to the flask while continuing to stir. determine which band coresponds to each of these compounds.

this particular chemical tends to bump too much. When the solution begins to boil. then rinsing the sodium sulfate with 3 mL of fresh dichloromethane. and the non-volatile components accidentally get sucked up into the pipet. The hot vapors will enter and condense inside of the cool pipet to give a light yellow liquid. What is the initial precipitate that forms when sulfuric acid is added to methyl anthranilate? Write a balanced equation for the reaction. such that a smooth distillation is difficult. however. the reaction tube is better. The product may be purified by first transferring the remaining dichloromethane solution to a 50-mL Erlenmeyer flask. in the hot organic vapors. Then add 3 boiling chips and evaporate solvent by gently boiling on a sandbath to leave a dark red oil. When possible. Weigh the product and calculate a percent yield based on methyl anthranilate.* Transfer the yellow liquid to a tared shorty vial. This step can be repeated. as the smaller opening at the top of the tube minimizes the loss of organic vapors to the atmosphere. and placing the tube into a sand bath. i. 2. and slowly release the bulb. the boiling will subside for a few moments as the temperature begins to climb to the boiling point of the methyl salicylate. Final Report: Attach the labeled TLC plates to your final report. [*Note: This technique is called "instant microscale distillation" (see Lab Guide Chapter 1). Ideally.. and adding the rinse solution to the flask with the dichloromethane.values. using a pipet to condense the vapors. Analyze your sample according to your Assignment sheet and the instructions on Sample Preparation in Lab Guide. At the end of your report answer the following questions: 1.. Why is diazonium sulfate formed in this procedure used in situ rather than isolated and purified before going on the next step? . combining all of the condensed liquid product. even with the boiling chips present.e. Once the dichloromethane has completely evaporated. Squeeze the bulb. until there is essentially no more vapors to withdraw from the flask. this is done by transferring the red oil and chips to a reaction tube. What role does concentrated sulfuric acid serve in this reaction? 3. you may be instructed to analyze your final product by IR or NMR. insert the tip into the flask just above the level of the liquid. You may need to turn the Varistat to 65 to 70. use a fresh pipet with a bulb attached to draw vapors up into the pipet.] Analysis In addition to TLC analysis.