David H. Kenny ond Jeffrey C. Strieter Michigan Technological University Houghton, Michigan 49931
I I
The Preparation
A sequential experiment for the undergraduate organic laboratory
W e have found that the preparation of 3-phenylanthranil makes an excellent sequential experiment in the undergraduate organic chemistry laboratory course. This is because the final product results from a series of reactions which are all presented in the organic chemistry lecture in the middle of the academic year. The reaction sequence can be carried out with no other equipment than that present in the undergraduate laboratory kit. 111 our organic laboratory, each student desk is equipped nith a Corning Organic Chemistry Kit. This experiment is based on the synthesis of 3-phenylanthranil reported by Smith and coworkers in 1951.' The reaction sequence consists of the following steps
(4) a diazotisation andUreplacement (5) the preparation of a heterocyclic compound by the pyrolysis of ttn rtzide
The fourth step in the reaction sequence, the diazotization and replacement by azide must be carried out in the hood because of the toxicity of HNa released from the reaction mixture. Students should be alerted to the hazards of working with asides in general, and hydrogen azide in particular. Although the reaction sequence can be completed by an average student in ten weeks, allowing three to four hours of laboratory work per week, a student with very good laboratory technique can complete the reaction sequence in six or seven weeks. The Experiment The o-henzoylbenzoic mid can he prepared by the student as outlined in many general organic chemistry laboratory texts,' or it can be obtained commercially. In either case, the acid must be anhydrous before continuing; i t should he heated in a drying oven for several hours with frequent crushing and stirring. If the water of hydration is not removed the reaction with thionyl chloride results in the formation of a. third ring, and the reaction yields 9,lO-anthraquinone.
The dehydrated acid (100 g) is dissolved in dry chloroform (200 ml), and the thionyl chloride (40 ml) is added. The reaction mixture is refluxed on the steam bath until the evolution of hydrogen chloride ceases. The chloroform and unreacted thionyl chloride are then distilled off. To the crude, solid product is added 20 ml of dry benzene, and this is removed by vacuum distillation. This last step is repeated once. The acid ohloride is then dissolved in dry benzene and cooled in an ice bsth. Concentrated ammonium hydroxide (200 ml) is
130 / Journal o f Chemical Education
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cooled in an ice hsib, and the acid chloride solntion is allowed to drip into t,he cold ammonia solution. Considerable heat is evolved and the final product is s, whitish-gray sticky mass. This crude product is filtered from the excess ammonia solution and washed with wster. llecrystrtllisation of the crude amine is very troublesome. To &void this, the crude amine is purified by washing it several times with hot wster, then by grinding i t in s. mortar with hot water and filtering it. At this point the product should have a melting point of 160-161DC. One recrystallizstion from 40% alcohol raises the meltine m i n t to 162-163'C (yield 7 2 7 9 e; 72-79%). The amide should he nure before ~roceedinnas the ouritv greatly affects the yield of the amine. h he amide should gave meltingpoint no lower than 161°C.
a
The pure amide (40 g) (the remainder of the amide is saved in case of a failure later on) is dissolved in a solution of 2M sodium hydroxide. This solution is cooled in ice, and sodium hypochlorite sohltion (90 ml of solution containing 0.075 g of chlorine per ml as sodium h~pochlorite)is added slowly with constant stirring. The solution is then heated on s. water bath for l l / n hr; the amine will separate as small yellow droplets. The solution is cooled, and the amine will crystdlize. Yield 29-34 g (84-90%) mp 93-101°C. Recrystallieation from alcohol raises the melting point to 106-107°C.
A solution of 150 ml of hydrochloric acid and 100 ml of distilled wster is cooled to 0" in ice, and 26 g of o-aminohenmphenone are dissolved in the acid, and then 10.6 g of sodium nitrite dissolved in water is slowly added. The solution is allowed to stand one hour in the ice bath. Next, 10 g of sodium aside dissolved is slowly added with constant stirring (MUST BE DONE I N T H E HOOD, due to the hydrogen azide evolved). This solution is allowed to stand overnight in a dark place, after which an oil will he found on the bottom of the container. The oil is extracted with ether, and the ether solution is dried over magnesium sulfate. The ether is evaporated, leaving the ail. Since pure o-aeidoheneophenone has a melt,ing paint of 3336'C, the recrystallization is omitted and the ail is used as is. The yield of crude product is 24 g (93'%).
The o-aaidobeneophenane (3 g) is dissolved in 100 ml of decalin. The solution is heated for 25 min s t 140°C. Evaporation of the decalin leaves a yellow gum. The gum is triturated with petroleum ether several times to remove the last traces of decalin. The 3-phenylanthranil is recrystdlized from 15-20 ml of ethanol in a Dry Iee-methanol bsth. The first recrystalli~ation gives 0.79 g of yellow solid product, mp 42-WC. Further recrystallization yields pure phenylsnthrrtnil, mp 53-54'C. 'SMITH, P. A. S., BROWN,B. B., PUTNEY, It. K., A N D REINR., J. Amer. Chem. Soc., 75,6333 (1953). 4 F ~ s s m ,LOUIS B., "Organio Experiments," D.C. Heath and Company, Boston, 1964, p. 195 ff.
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