Published Peer-Reviewed Journal Articles
 

Using Heterocyclic Chemistry as an End-of-the-Year Review Tool in First-Year Organic Chemistry. The Chemical Educator 2004, 9 (1), 1-3.

Synthesis of 2-Acetylthiophene by the Acylation of Thiophene Using Acetic Anhydride and Iodine (A Revisiting after Almost Sixty Years). The Chemical Educator 2004, 9 (3), 163-165.

The Amazingly Versatile Titanocene Derivatives. Journal of Chemical Education 2006, 83 (5), 735-740.

A Colorful Look at the Chelate Effect. Journal of Chemical Education 2006, 83 (8),
1158-1160.

Teaching Solvent Effects on SN2 Reactions by the Introduction of Ionic Liquids. The Chemical Educator 2006, 11 (2), 64-66.

Three Titration Experiments Involving 1,2-Propanediamine Utilizing Computer Data Collection. The Chemical Educator 2007, 12 (6), 384-386.

 

 

 

Student Instructions for "Synthesis of 2-Acetylthiophene by the Acylation of Thiophene Using Acetic Anhydride and Iodine" 

                               Organic Chemistry Lab     CHM 244

The Preparation of 2-Acetylthiophene by Friedel Crafts Acylation of  

                   Thiophene with Acetic Anhydride and Iodine
 

Background

      Synthetic methods for the preparation of 2-acetylthiophene have been published in chemical journals since the end of the nineteenth century. Hartough and Kosak did extensive work in this field during the 1940s. Both acid chlorides and acid anhydrides have been used as the source for acyl cations and a lengthy list of Lewis acids have been tried as “catalysts.” One of the synthetic methods studied by Hartough and Kosak has received very little attention in lecture text discussions or laboratory text experiments regarding Friedel Crafts acylation of heterocyclic compounds: acylating thiophene with acetic anhydride and iodine. The most frequently mentioned method in texts and journals is acylation with acetyl chloride and tin(IV) chloride. Johnson and May reported yields of 79-83% using this combination. This instructor’s efforts with tin(IV) chloride led to a tar-like product similar to others’ attempts to acylate with the stronger Lewis acid aluminum chloride. Hartough and Kosak obtained 74-79% yields with acetic anhydride and 85% phosphoric acid. They also reported as high as 87% yield using acetic anhydride and fused zinc chloride. But for first-year organic labs, the acetic anhydride and iodine reagents are much easier to handle and yield comparable if not superior results. Published results give yields of up to 86% when the amount of iodine is carefully controlled.

    The use of iodine as the Lewis acid is an interesting study in itself. Attempts to acylate with acetyl chloride and iodine have met with little success. Hartough and Kosak reported a 16% yield of 2-acetylthiophene along with considerable amounts of unidentified decomposition products using this combination. It appears that iodine must be combined with acetic anhydride as the acylating agent. Also, the amount of iodine must be carefully controlled. Best results occur when 8 x 10-3 mole of iodine is used per mole of acetic anhydride. The product yield falls to just a trace if the iodine ratio is only 8 x 10-5 mole per mole of acetic anhydride, but when the amount of iodine rises to 4 x 10-2 mole per mole of acetic anhydride rapid uncontrollable reactions set in. The fact that iodine is a Lewis acid is a difficult thing to see. Instead of looking like a substance that can accept a pair of electrons, the Lewis structure of iodine has lone pairs of electrons all around the two atoms. The answer lies in the fact that a low-lying empty σ* (antibonding) orbital [LUMO – lowest unoccupied molecular orbital] can accommodate an electron pair from a Lewis base (such as the electrons on an oxygen atom in a carbonyl group.) The following equation shows the Lewis acid-base reaction.

                                

The Lewis complex is then attacked by the thiophene, acting as a nucleophile, in a type of (Lewis) acid-catalyzed nucleophilic acyl substitution.

          

            Better results are obtained when one of the starting materials is in excess. Equimolar quantities with the proper amount of iodine resulted in 76% yields. Numerous trials found that thiophene excess was preferable. Polyacylation is not a problem because the attachment of one acyl group to the thiophene ring deactivates the ring the same way electron withdrawing groups deactivate benzene rings. Low yields of 2,5-diacetylthiophene have been produced by action of acetic anhydride with zinc chloride on 2-acetylthiophene using long reflux times. The problem of different isomers from monoacylation does not arise because the substitution is very regioselective. The 2 position is favored over the 3 position in thiophene because greater delocalization of (+) charge is possible at the 2 position; therefore the rate is greater there. There are three resonance forms for the intermediate carbocation resulting from attack at the 2 position; only two resonance forms exist for attack at the three position.

                         

 

Experimental Procedure - Conduct all steps leading up to and including final product distillation in a fume hood

Starting Materials:

            Thiophene             (0.240 mol)            20.2 g          19.0 mL

          Acetic Anhydride   (0.120 mol)          12.3 g          11.3 mL

          Iodine                  (9.60 x 10-4 mol)        0.244 g

 

          To a mixture of 19.0 mL of thiophene and 11.3 mL of acetic anhydride in a 50 mL boiling flask, add 0.244 g of ground iodine; agitate with a magnetic stirring bar for 5 min. The mixture will turn purple and shortly thereafter turn brown. Add boiling stones to the flask and heat the mixture with a heating mantle (medium setting) under reflux conditions (use water jacket) for one hour. (Longer heating time leads to decomposition of thiophene, evolution of H2S gas and lower yields.) Cool the mixture, dilute with 24 mL of deionized water and agitate for 15 min. Transfer to a separatory funnel and draw off the lower organic layer into a 125 mL Erlenmeyer flask. Wash the aqueous layer twice with 6 mL of chloroform and add these organic layers to the organic product. Return the combined organic layers to the separatory funnel and wash with 40 mL of 10% sodium carbonate; drain and save the organic layer. Then wash thoroughly with 40 mL of 10% Na2S2O3, again keeping the organic layer. Dry the organic product in the 125 mL Erlenmeyer flask with 2.4 g of anhydrous sodium sulfate for 20 min. with occasional agitation. Gravity filter back into the boiling flask to remove the drying agent. Add fresh boiling stones to the flask. The chloroform and thiophene are removed by fractional distillation using a Vigreux condenser (see picture on next page). Use aluminum foil to wrap the distillation head. Begin thermostat at medium setting; then move to medium-high as needed. Roughly 10 to 15 mL of distillate will slowly come over between 60-75oC. Convert to a low burner flame for continued heating and place a wire gauze under the boiling flask. Slowly heat, collecting the fraction that boils between 200-215oC in a massed 50 mL Erlenmeyer flask. This should leave only a small amount of tar residue in the flask. The product will probably have an orange-yellow color. Mass the product and calculate a percent yield. Decolorize the product by adding 5%, by mass, activated charcoal. Agitate and gently warm the flask. Gravity filter through a fluted filter paper. Label the product with group’s names, product name, distilled mass, % yield, and date.

          In order to test for the identity of the proposed product, a semicarbazone will be formed (remember the product is a ketone as well as a heterocyclic compound derivative) and the melting point checked against a literature value. 

            

Dissolve 1 g of semicarbazide HCl and 1.5 g of sodium acetate in 10 mL of deionized water in a 150 mm test tube (this will require stoppering the tube and agitating vigorously.) Add 1 g (0.8 mL) of product in 1 mL of ethanol, stopper and agitate vigorously again. Place in a boiling water bath, remove the heat, and allow the tube and contents to cool until complete crystallization is accomplished (place in an ice bath for the last few minutes.) Filter the crystals with suction filtration, wash the crystals thoroughly with water.Dissolve the impure product with 10 mL of hot ethanol. Allow the pure product to recrystallize in an ice bath and again vacuum filtrate. Dry the crystals in a 110oC oven for 10-15 min. Take a melting point of the semicarbazone crystals. Do not add too much oil to the Thiele tube (the oil’s volume will expand as it is heated.) Make sure that the rubber band joining the thermometer to the melting point capillary tube is well above the level of the oil. Report the derivative’s melting point temperature. IR and NMR spectra will be run if instrument availability at Lynchburg College allows. 

 

                                                           a Vigreux distillation head

 

Hazards

      Iodine  is highly toxic by ingestion and inhalation. It is a strong irritant to eyes and skin. Acetic anhydride is strongly irritating and corrosive. It may cause burns and eye damage. Thiophene has a foul stench and is moderately toxic by inhalation. It has a NFPA flammability hazard rating of 3. Care must be taken to ensure that the thiophene has been completely distilled over before changing from a heating mantle to a burner flame. Chloroform is toxic by ingestion, inhalation, and by skin contact. It is suspected by NTP to be carcinogenic. Prolonged exposure can lead to liver and kidney damage. The experiment will be conducted in a fume hood. Proper eye wear is required at all times. Protective gloves are recommended. All waste is to be deposited in the proper waste containers on the side ledge.

 

 

Digital Pictures to Accompany "A Colorful Look at the Chelate Effect"

click on pictures

Picture 1

Picture 2  

 

 

Student Instructions for "Three Titration Experiments Involving 1,2-Propanediamine Utilizing Computer Data Collection"

Experiment #1

Experiment #2

Experiment #3