Some Small-Scale Organic Preparations1 L. 0. BINDER Montana State College, Bozeman, Montana INTRODUCTION
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OR a number of years the author has been searching for ways to increase student interest in oiganic laboratory work. Frequent complaints that "it takes too long" seemed to indicate that the semimicro procedures so successfully advocated by Cheronis2 and others might offer a partial solution. Preliminary trials with selected students soon showed that in addition to the advantages of simple equipment and less time for preparation, there was also the disadvantage that the students felt considerable disappointment over the small amount of product. Starting with the idea of obtaining an appreciable yield, a number of procedures have been worked out and several additional pieces of suitable equipment have heen added to the list generally used. Since i t is felt that the term "semimicro" is not strictly applicable, the expression "small-scale" is suggested in its place. The preparations given are representative of those used in the first two quarters a t Montana State College. The list is augmented each year through the assignment of a "problem" to each student in which he is asked to select a particular reaction of interest to him and work out the details of a small-scale procedure. Particular emphasis is placed on solid products since crystallization technique is more difficult to master than distillation.
been added, add an additional 1.5 g. of solid sodium bisulfite, stopper, and shake for ten minutes. Cool the tube in cold water and allow the emulsion to break as completely as possible. Decant the liquid into a separatory funnel without allowing too much of the solid to be carried along. Carefully separate the upper layer and transfer i t to an 8-inch tube. Add 1.5 volumes of concentrated hydrochloric acid and warm under reflux with a boiling water bath for three hours. Fit the tube with a stopper holding a capillary which reaches to the bottom of the tube and a connection to the suction pump, and remove the liquid as completely as possible under vacuum while continuing the heating. To the dry residue add 30 ml. of benzene and arrange for distillation. Be sure to clamp securely as "bumping" may occur. Distill until the benzene comes over water free, then reflux for a few minutes and filter hot. Cool the filtrate thoroughly and filter with suction. This filtrate may be used for a second extraction of the solid residue from the first (hot) filtration. Combine the first and second crops of crystals, recrystallize from benzene if necessary, and dry in air.
PROCEDURES
Phenyl urea. Bring a mixture of 1.5 g. (1.5 ml.) of aniline, 2.3 g. of nitrourea, and 20 ml. of water to a boil. 411ow to stand for 20 minutes. Cool thoroughly and filter. Re-crystallize the product, using Norite, from 15 to 20 ml. of water. Phenyl urea melts a t 147'C. (As an interesting variation, fi-phenetidine may be substituted in equivalent amount for the aniline. The resulting product, known as "Dulcin," has an intensely sweet taste.) a-Hydroxyisobutyric acid. Place in an 8-inch tube 6 ml. of water, 3.6 g. (4.6 ml.) of acetone, and 4.0 g. of potassium cyanide. Shake to dissolve as much of the cyanide as possible. Dissolve 6.5 g. of sodium bisulfite in 10 ml. of water. Warm the cyanide solution to about 40°C. and add the bisul6te solution in small portions, stoppering securely and shaking for two or three minutes between additions. When all the bisulfite solution has
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' Presented before the Division of Chemical Education at the 109th meeting of the American Chemical Society in Atlantic City. April8-12,1946. Cmno~rs,N., "Semimicro and Macro Organic Chemistry," Thomas Y. Crowell Company, New York, 1942. Alsonumerous EDUCATION. articles in the TOURNAL oa CHEMICAL
m o m I. PREPARATION OP ADIPICAcm
Do not leave exposed to the atmosphere for longer than necessary to dry completely. a-Hydroxyisobutyric acidmelts a t 7 9 T . Adipic acid. Fit a three-neck tube8with a separatory funnel in one arm and a bent piece of glass tubing connected to the suction pump by rubber tubing in the other. Bore the center cork to hold a bearing of 8 mm. or larger glass tubing and a thermometer. Bend a piece of 6-mm. glass rod into a loop a t one end. This loop must fit inside the tube and pass around the thermometer which reaches nearly to the bottom of the tube. The rod should fit very loosely in the glass bearing. (See Figure 1 for diagram of the assembly.) Place 11 ml. of concentrated nitric acid in the tube and 5 g. (5.2 ml.) of cyclohexanol in the separatory funnel. Have ready a beaker of ice water to moderate the reaction if necessary. Turn the suction pump on full and add the cyclohexanol a few drops a t a time to the nitric acid. Stir constantly and rapidly, and watch the temperature closelv. Add the cvclohexanol a t such a rate that the temperature stays between 85' and 90°C. The addition should take about 15 minutes. When all The three-neck tubes have been fabricated by the author, but should be readily obtainable at moderate cost from Coming, Ace Glass, Scientific Glass Apparatus Company, etc.
the cyclohexanol has been added, maintain the temperature a t 80-90°C. for 15 minutes with a small burner; then cool the reaction mixture in an ice bath and filter the product. Wash with about 10 ml. of ice water and allow to dry. Adipic acid melts a t 1513°C. o- and p-Nitrophenol. Dissolve 9.6 g. of sodium nitrate in 24 ml. of water in an Erlenmeyer flask. Carefully add 6.5 ml. of concentrated sulfuric acid. Cool to 20°C. and add drop by drop 6 g. of phenol which has been liquefied by warming with 1 ml. of water. Keep the temperature between 20" and 25OC. during the addition of the phenol. Let stand for an hour or more with shaking, then add 2 volumes of water. Decant the aqueous layer carefully and wash the residue thoroughly with water twice, decanting the water each time. Steam distill the residue. (See Figure 2.) The o-nitrophenol that passes over is allowed to crystallize and then filtered with suction and dried. I t should melt around 45°C. Impure material can be re-distilled with steam. The residue in the original steam distillation tube contains p-nitrophenol which is not volatile with steam. To recover this material, add 2 N sodium hydroxide until the solution is just alkaline to Congo paper, then add an additional 12 ml. of 2 N sodium hydroxide. Add 0.5 g. of Norite and pass steam through as in steam distillation for five to ten minutes. Filter the hot solution and concentrate to 10 or 15 ml. On cooling, this solution should deposit crystals of the sodium salt. (If no crystals appear, rewarm this solution, add 3 or 4 ml. of 1 N sodium hydroxide, and allow to cool again.) Filter the precipitate with suction and wash i t with a little 2 N sodium hydroxide. Liberate the free p-nitrophenol from the salt by adding dilute hydrochloric acid dropwiie to a hot water solution of the salt. The product appears as an oil that crystallizes on standing. Recrystallize using Norite or Darco from very dilute hydrochloric acid. $-Nitrophenol melts a t 114°C. n-Propyl acetate. In an 8-inch test tube reflux 5.2 g. (5 ml.) of glacial acetic acid, 4.8 g. (6 ml.) of n-propyl alcohol, and 7 to 8 drops of concentrated sulfuric acid for 45 minutes. Arrange for distillation and distill until the temperature reaches llO°C. Treat the distillate with 3 or 4 ml. of saturated sodium carbonate solution or until you get a basic reaction to phenolphthalein. Transfer to a separatory funnel, withdraw, and discard the lower layer. Wash the crude ester with 3 or 4 ml. of water, withdraw, and discard the water, then add five or six granules of anhydrous calcium chloride and allow to stand with shaking for five or ten minutes. Decant into a dry test tube, add more calcium chloride, and allow to dry for an additional 10 or 15 minutes. Filter into a small distilling tube and distill. n-Propyl acetate boils a t 101.6"C. (760,mm.). Cyclohexanone. Dissolve 8 g. of sodium dichromate in 20 ml. of water; add 4 ml. of concentrated sulfuric acid. Place in a 10-inch pyrex test tube 5 g. (5.2 ml.) of cyclohexanol and add the dichromate-sulfuric acid
mixture in small portions, cooling under the tap to 20-25'C. between additions. Use a thermometer as a stirring rod and do not allow the temperature to rise over 50°C. When all of the dichromate-sulfuric acid mixture has been added and the temperature no longer tends to rise above 50°C., place the tube in a beaker of water a t 50-55'C. for 15 to 20 minutes. Add 20 ml. of water and arrange for distillation. Distill until the solution commences to foam. Separate the cyclohexanonelayer in the receiver carefully and extract the water layer with 10 ml. of ether. Combine the ether extract with the cyclohexanone, dry with a small amount of anhydrous calcium chloride, and transfer to a distilling tube. Remove the ether with a water bath and distill the product. Cyclohexanone boils a t 156.7'C. (760 mm.). Class reaction has been very satisfactory, particularly where students have had an opportunity to com-
pare macro and small-scale procedures. The fact that a respectable yield is possible is important from the student's point of view. The knowledge that careful work will produce results encourages him to acquire good technique and to be willing to repeat a preparation if the yield is low. No preparation was assigned for which the author was not able to get a 60 per cent yield, and in most cases the class average yield is 50 per cent or better. As given a t Montana State College, the laboratory work is supplemented with in-the-laboratory lectures and demonstrations on distillation, boiling points, crystallization, and melting points, calculation of theoretical yields, and other pertinent matters of theory and technique. During the first quarter an excessive amount of supervision is not necessary, and d f i n g the second, very little except for checking equipment setups.
