Chapter 1.

Background

Acetanilide is an analgesic, formally known as Antifebrin¹, and is structurally similar to acetaminophen (or Tylenol). However, unlike acetaminophen, acetanilide is toxic. Acetanilide is prepared from aniline using an acetylation reaction. Acetylation is often used to place an acetyl protecting group on primary or secondary amines to reduce their reactivity toward oxidizing agents or electrophiles. Acetamides are usually crystalline solids which can be a help in purification by recrystallization. The melting points can be used for characterization and identification of the corresponding compounds.

1. Cahn, A.; Hepp, P. (1886), “Das Antifebrin, ein neues Fiebermittel”, Centralbl. Klin. Med.1886, 7, 561–65

Reaction

Acetylation of aniline and unknown substituted anilines with acetic anhydride

Lab Objective

In part 1 you will convert aniline to acetanilide using an acetylation reaction described in the next tab.

In part 2 you will be given an unknown aromatic amine from table 1-1. The amine will be converted into its acetamide analog also using the acetylation procedure. Your objective is to compare the two reactions and determine the identity of the unknown amine/acetamide product.

Procedure

Reagents:

• Aniline
• HCl (concentrated HCl is 37% w/w)
• Acetic anhydride
• Sodium acetate

Part 1:

Dissolve 500 mg of aniline in 14 mL of water. Note that aniline is immiscible in water and two layers should be observed. Add 0.45 mL of concentrated hydrochloric acid and stir. Measure out 0.6 mL of acetic anhydride and prepare a solution of 530 mg of sodium acetate in 3 mL of water. Add the acetic anhydride to the solution of aniline hydrochloride in water, mix by swirling, and immediately add the sodium acetate solution. The solution becomes white as acetanilide precipitates. Cool the solution in an ice bath and collect the solid acetanilide by vacuum filtration. Recrystallize from ethanol 95%—it may be necessary to add a small amount of water.

Part 2:

Use the above procedure for acetylation of the substituted unknown aniline. Exact quantities cannot be calculated since the starting material is an unknown.

Techniques

Reagents

Characterization

Collect TLC data for both products of part 1 and 2. Co-spot each product against the starting material for the reaction, respectively, and against each other. Collect the Infrared spectrum of the part 1 product, acetanilide, and the unknown starting material and product from part 2. Characterize the products of part 1 and 2 by m.p. and using the Beilstein test for halogens.

Table 1-1