Expt. Amide synthesis - OFF®, an Insect Repellent PDF

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OFF®, an Insect Repellent...

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® Amide Synthesis: OFF , an Insect Repellent

Objective: To synthesize the insect repellent OFF and to illustrate the synthesis of an amide through an acid chloride. Introduction: Insect repellents are commonly used by everyone today. In this experiment, we synthesize an insect repellent known as N, N-diethyl m-toluamide. This is also known as OFF or deet. This repellent is effective against a lot of insects like mosquitos, fleas and ticks. The effect of OFF on a mosquito works because mosquitos have antennae that contains sensors for carbon dioxide and water vapor. The carbon dioxide part is temporarily disabled. The water vapor part is completely turned off by the OFF insect repellent. Because of this the mosquito is not able to find its victim. In this lab experiment, m-toluic acid is the amide of diethylamine. We react an acid with a base which forms the ammonium salt. This salt is then converted to carboxylic amide when this salt is heated to a high temperature. We convert this carboxylic acid to its acid chloride by using excess thionyl chloride. The acid chloride is then reacted with an appropriate amine to give amide. Equation:

Safety considerations: Thionyl chloride is noxious and corrosive. Hence it should be handled with care. Wash it off with water if it comes in contact with skin. Do not inhale the fumes. Diethylamine is also noxious and corrosive. It should be kept cool because it has a low boiling point of 56 degrees celsius. Both of these should be kept separately in different hoods.

Procedure and observations: Procedure

Observations

Use a dry 10 mL round-bottom flask with a magnetic stirrer. Place the Claisen head on the flask. Cap the straight arm of the Claisen head with a The damp glass wool scavenges HCl vapors. septum and the other arm with a water condenser, followed by an air condenser, and a drying tube - damp piece of glass wool. Place about 0.4 g of m-toluic acid in the reaction flask. Add a twofold excess of thionyl chloride

Some is lost during the reaction time because it is volatile and to speed up the reaction.

Heat to about 90°C in a water bath. Cool to room temperature. Turn off the hot plate. Add 4 mL of anhydrous ether using the syringe.

Stirred until homogeneous.

In the hood, mix diethylamine, a threefold excess compared to m-toluic acid, with 1.5mL of anhydrous ether. Add this mixture of diethylamine and ether to the reaction mixture using the syringe and stir. Diethylamine hydrochloride will precipitate from the reaction mixture.

dropwise.

Procedure

Observations

Stir for an additional 10 minutes.

The reaction smoked up upon addition of the amine.

Add 2 mL of a 5% aqueous sodium hydroxide solution using the syringe. Stir for 15 minutes.

Two layers will form.

Pull the damp glass wool out of the drying tube using forceps. Remove the septum from the Claisen head and then use vacuum to remove any remaining HCl or SO2 vapors from the reaction assembly. Transfer the reaction mixture to a centrifuge tube Remove the lower aqueous layer and add another 2 mL of the 5% NaOH aqueous solution, cap the vial or test tube.

Shake it for 5 mins.

Allow the layers to separate and remove the lower aqueous layer. Extract the ether layer with 2 mL of a 10% HCl aqueous solution. Wash the ether layer with 2mL of water. For each extraction, shake the mixture, allow the two layers to separate and remove the aqueous layer, add ether. Transfer the ether layer with a dry pipet to a vial and add granular anhydrous sodium sulfate. When dry, transfer the ether solution to a small beaker Wash the drying agent with a little additional ether to ensure all product has been transferred.

Sodium sulfate is a drying agent used in acidic conditions - 2 spatula tips. Solution turned clear.

Procedure

Observations

Evaporate the ether on a moderately warm hot plate.

The residue will be dark brown; this is the crude amide.

Prepare a small alumina column in a pasteur pipet to purify this product. A column of about 2cm height should be sufficient and use the dry pack method to pack the column. Dissolve the crude product in a minimal amount of hexane. Add the solution of the crude product to the top of the column.

Use hexane to moisten the column.

Use hexane as the eluent, once all the product has been absorbed on the column. Collect the eluting solvent containing the product in a preweighed beaker.

yellow solution.

Evaporate the hexane on a warm hot plate using an air stream to speed up evaporation.

N,N-Diethyl m-toluamide should be a light tan liquid.

Data collection/Calculations: 0.400 grams: m-toluic acid 0.43 mL: Thionyl chloride 360 mg = 0.36 grams: DEET Theoretical yield of m-toluic acid: 0.400g x 1mol/135g = 0.00296 mol of m-toluic acid 0.00296 x191.27g/1mol = 0.566g of DEET Percent yield of DEET = 0.36g/0.566g x 100 = 63% IR spectrum of DEET:

NMR spectrum of DEET:

! ! ! Discussion: In this lab experiment, we convert carboxylic acid into its amide. This reaction produces OFF or DEET which is an insect repellent. This reaction is an acid base reaction which produces salt. It is treated with high temperatures. However this is not convenient, hence we produce amides from a more reactive acid chloride. This is formed when carboxylic acid is reacted with excess thionyl chloride. The acid chloride is then reacted with an amine which produces its amide. The starting carboxylic acid here is m-toluic acid. It is reacted with excess thionyl chloride and is drives the reaction towards the formation of products. This acid chloride is then slowly reacted with a mixture of ethanol and diethyl amine. An organic ether layer is left when we add sodium hydroxide which further removes HCl and SO2 from the reaction. The organic ether layer is separated and we obtain crude amide. This product is put through a column and is heated up to give us the remaining N,N-diethyl m toluamide; DEET. In our lab, we obtained 0.36g of DEET giving us a 63% yield. IR spectrum of amine shows a long peak at about 1600cm-1. This peak represents a C=O bond from the amide. There is another peak at about 2900cm-1, which indicates aromatic C-H bonds. Overall, the IR spectrum that we obtained shows that our experiment was successful and we synthesized a pure amount of N, Ndiethyl m-toluamide with a yield of 63%.

Some errors may have occurred in this lab which may lead to a lower yield. One example would be if amide/ethanol mix was added to the acid chloride. This procedure is done slowly and if not there can be violent smoke. Stirring should be done well and for longer to make sure all the HCl and SO2 is removed from the reaction. References: Department of Chemistry. (2015-2017). CHM 205/206 Lab Manual. Miami, Florida: University of Miami at Coral Gables. Padias, Anne B “Making the connections: A how to guide for organic chemistry lab techniques”. New York: Hayden McNeil, 2007. Post lab questions: 1. The washing with NaOH will remove any m-toluic acid that has not been reacted as the soluble carboxylate. Any residues from the acid chloride will also be removed. Excess thionyl chloride will be destroyed and become HCl and SO2 which will be removed by the NaOH solution. 2. A) C-O stretching at 1150 cm-1. B) CO-N stretching at about 1700 cm-1. C) Aromatic C-H stitching at 2968 cm-1. D) C=O stretching at about 1800 cm-1. E) C=C stretching at 1633 cm-1. F) Aromatic C-H bending at 766 cm-1. 3. These impurities may be because of carboxylic acid that is not removed. We can extract by dissolving the compounds in ether and adding saturated NaHCO3 or NaOH to obtain separate layers. The ether layer has to be evaporated to isolate the compound. The aqueous layer contains the sodium salt which can be treated with HCl. 4. 5. An acid base reaction would occur. The salt compound that this reaction produces would have to be heated at extremely high temperatures to obtain the amide which may not be ideal for the lab.

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8. A 9. C 10. C...