Acetanilide recrystallization

Pyridine has been phenylated with the following free-radical sources benzenediazonium chloride with aluminum trichloride the Gomberg reaction " phenylhydrazine and metal oxides A -nitroso-acetanilide dibenzoyl peroxide phenylazotriphenylmethane di-phenyliodonium hydroxide and electrolysis of benzoic acid. ° Although 2-phenylpyridine usually accounts for over 50% of the total phenylated product, each of the three phenyl derivatives can be obtained from the reaction by fractional recrystallization of the... 

To a solution of 42 g of 2.amino.2 -chlorobenzophenone in 500 ml of benzene, 19 ml of bromoacetyl bromide was added dropwise. After refluxing for 2 hours, the solution was cooled, washed with 2N sodium hydroxide and evaporated. The residue was recrystallized from methanol giving crystals of 2-bromo.2. (2-chlorobenzoyl) acetanilide melting at 119° to 121°C. 

To a solution of 14.5 g of 2-bromo-2 -(2-chlorobenzoyl)acetanilide in 100 ml of tetrahy-drofuran, an excess of liquid ammonia (ca 150 ml) was added. The ammonia was kept refluxing with a dry-ice condenser for 3 hours after which time the ammonia was allowed to evaporate and the solution was poured into water. Crystals of 2-amino-2 -(2-chloro-benzoyOacetanilide were collected, which after recrystallization from ethanol melted at 162° to 164 C. 

A solution of 3 g of 2-amino-2 -(2-chlorobenzoyl)acetanilide in 50 ml of pyridine was refluxed for 24 hours after which time the pyridine was removed in vacuo. The residue was recrystallized from methanol and a mixture of dichloromethane and ether giving crystals of 5-(2-chlorophenyl)-3H-1,4-benzodiazepin-2( 1 H)-one melting at 212° to 213°C. 

In a 500-cc. round-bottomed, three-necked flask fitted with a reflux condenser, dropping funnel, and a mercury-sealed stirrer (Note 1) is placed a solution of 46 g. (0.5 mole) of dry aniline in 125 cc. of pure dry benzene. Stirring is started, and a solution of 42 g. (0.5 mole) of ketene dimer (p. 64) in 75 cc. of pure dry benzene is added dropwise over a period of half an hour. The reaction mixture is then heated under reflux on the steam bath for one hbur. After the major portion of the benzene has been removed by distillation from the steam bath, the remainder is removed under reduced pressure. The residue is dissolved in 500 cc. of hot 50 per cent aqueous alcohol from which the aceto-acetanilide separates on cooling. The mixture is cooled to 0° before filtration. A second crop of crystals can be obtained by adding 250 cc. of water to the mother liquor and cooling again (Note 2). The total yield of product, m.p. 82-83.5°, is 65 g. (74 per cent of the theoretical amount). Further purification by recrystallization from 300 cc. of 50 per cent alcohol yields 55 g. of a product which melts at 84-85°. 

Addition of 5.00 g (0.0158 mole) of 3 -[l-hydroxy-2-(2-imino-3-thiazolidinyl)ethyl]acetanilide hydrochloride to 15 ml of concentrated sulfuric icid is carried out in small increments over 0.5 h. The orange solution is stirred an additional 1 h, poured onto ice and made basic with concentrated ammonium hydroxide. The aqueous base is extracted twice with chloroform and the combined organic layers washed with water, brine, dried (sodium sulfate) and evaporated at reduced pressure to give 3.32 g (80% crude yield) of the 3 -(2,3,5,6-tetrahydroimidazo[2,l-b]thiazol-6-yl)acetanilide, melting point 164-166°C (recrystallization from 2-propanol). 

The crude material can be used witlwut further treatment for the following nitration step. Especially pure acetanilide, such as is required for pharmaceutical purposes, can be obtained by recrystallization from boiling water, yielding completely colorless and odorless, shiny plates. 

Examples Suppose that you have prepared a crude sample (about 4.0 g) of A/-phenylethanamide (acetanilide) and you are to purify if by recrystallization -from water. The melting point of pure A/-phenylethanamide is 114 C (tide, 2000). 

Iodoaniline 5 03,504 A solution of IC1 (1 mole) is prepared from iodine (127 g) in glacial acetic acid (150 ml) (cf. page 182). When this is dropped, with stirring, into a solution of acetanilide (1 mole) in glacial acetic acid (150 ml) (exothermic reaction ) and the whole is stirred for a further few hours, p-iodoacetanilide is precipitated. After 12 h, the mixture is poured into water (21), and the product is collected and washed with water and dilute sodium hydroxide solution. Recrystallization of this crude material from ethanol gives a 90 % yield of the amide, m.p. 184°, which is hydrolysed by concentrated hydrochloric acid to p-iodo-aniline. 

Recrystallization. Recrystallization is invariably afforded by dissolving the product in the minimum quantity of the solvent. In this case, take about 2 g of the crude acetanilide obtained finm section 4.1.2.1.2.4, and dissolve it in minimum volume of hot rectified spirit [2% (viv)]. Practically snow-white crystals of acetanilide are obtained. 

Tylenol, on the other hand, is an amide and much more resistant to nucleophilic attack. Hydrolysis would require extended heating, and strong acid or base is required. [Indeed, amides derived from benzenamine. such as /V-acetylbenzeneamine (acetanilide), are commonly purified by recrystallization from neutral boiling water, further illustrating their stability.]... 

If you started with aniline, transfer the solid to a 10-mL Erlenmeyer flask and recrystallize the product from 95% ethanol (see Technique 11, Section 11.3, and Figure 11.4). Filter the crystals on a Hirsch funnel and dry them for several minutes with suction. The brominated products from either acetanilide or anisole should be crystallized using a Craig tube (Technique 11, Section 11.4 and Figure 11.6). Use 95% ethanol to crystallize the acetanilide product and hexane to crystallize the brominated anisole compound. Allow the crystals to air-dry and determine the weight and melting point. 

Analysis Determine the melting points of the crude and recrystallized acetanilide, the weight of the latter material, and calculate your percent recovery using Equation 3.1. 

The solubility of benzoic acid at 0 °C is 0.02 g per 100 mL of water, and that of acetanilide is 0.53 g per 100 mL of water. If you performed either of these recrystallizations, calculate, with reference to the total volume of water you used in preparing the hot solution, the amount of material in your experiment that was unrecoverable by virtue of its solubility at 0 °C. 

Bromination, Work-Up, and Isolation Add the bromine solution to the rapidly stirred solution of acetanilide over a period of 1-2 min continue stirring the reaction mixture for about 10 min after completing the addition. Slowly add 100 mL of ice-cold water with stirring and then add just enough ice-cold saturated aqueous sodium bisulfite to discharge the color of the mixture that results. Cool the mixture in an ice-water bath and collect the product by vacuum filtration. If the crude product appears yellow, wash it with aqueous sodium bisulfite. In any case, wash it well with cold water and press it as dry as possible on the filter. The product may be recrystallized from methanol. ... 

Purification and Characterization. Further purification of the product is generally not required. However, the acetanilide may be recrystallized from hot water or from ethanol-water using the Craig tube. 

NOTE. Acetanilide (150 mg) can be recrystallized from approximately 3 mL of water, or from 2 mL of ethanol-water (1 10 vh), with better than 80% recovery. 

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