H. Gruen and B. E. Norcross' H a r ~ u rColleae State University o f New York
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Binghamton
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A Modifitation and Extension of an Elementary Prepamtion of Ninhydrin
The instructive multistep synthesis of ninhydrin developed for use in an elementary organic chemistry laboratory sequence by L. F. FieserZhas been avoided in our laboratories because of the required synthesis of finely divided metallic sodium. The ordinary hazards attending the vigorous agitation of molten sodium in near-boiling xylem, augmented by the occasional element of carefree enthusiasm found a t this instructional level, prompted us to seek a substitute synthesis of the necessary sodio-2-carbomethoxyindane-1,3dione. The use of a semisolid 50% suspension of sodium hydride in mineral oil3 has proved to be a simple and safe method for effecting the desired double ester condensation of ethyl acetate and dimethyl phthalate. In addition, the inclusion of one more filtration in the synthetic scheme permits the isolation of an interesting side product. The compound A',2'-bi(iudan)-3,1',3'trione, or bi-indoue,4 is formed by self-condensation of indane-1,3-dione, catalyzed by acid or base:
If the mother liquor obtained from the filtration of the 1,Mione is allowed to stand undisturbed in the dark for from one to seven days, a small but useful amount of the slightly soluble bi-indone precipitates. Isolation of this compound by the students, as well as theoretical examination of possible mechanisms of formation, provided valuable opportunities for discussions of the control of a preparative organic reaction to give a high yield of a desired product by the proper choice of experimental conditions. Synthesis of Sodio-2-carbomethoxyindane-1,3-dione
Place 8.2 g of a 50% suspension of sodium hydride in mineral oil into a 100-ml round-bottomed flask. Add
' To whom inquiries should be addressed.
FIESEE,L. F., "Experiments in Organic Chemistry,'' Third Ed., Revised, D. C. Heath and Company, Boston, 1957, pp. 12% 129. - - ~ - - ~ a Sodium hydride dispersion is available from Metal Hydrides, Inr., Beverly, Mass. JOSEPHY, E., AND RADT, F., Editors, "Ekevier's Encyclopedia of Organic Chemistry," Elsevier Publishing Company, Inc., New York, 1948, Vol. 12 A, p. 396. 3
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to this a mixture of 20 ml of dimethyl phthalate and 40 ml of ethyl acetate. Attach a wide bore reflux condenser, provided with a calcium chloride drying tube, to the flask. Insure that no water forming on the outside surface of the condenser can pass into the reaction mixture. Place the reaction assembly onto a steam bath, and gently raise the mixture to reflux temperature, shaking intermittently. Note: some foaming may occur initially. After a reflux period of 3 4 hr, continuous or divided between two laboratory periods, cool the reaction mixture. Break up the yellow solid, add 3-5 ml ethyl acetate, and filter. The filter cake should be washed with ethyl acetate, and allowed to air dry. The yield varies from 15 to 23 g. Synthesis of lndane-1,3-dione and Bi-indone
To 14 g of sodio-2-carbomethoxyindane-l,3-dione in a 500-ml Erlenmeyer flask is added rapidly an 80°C solution of 20 rnl of concentrated hydrochloric acid in 200 ml of water. The resulting slurry is maintained at 70°C, plus or minus two degrees, for 5-6 min. Two crystalline fractions are collected. The slurry is allowed to cool to 6OoC, and is filtered hot. .4 second fraction can be collected by cooling the filtrate to 5°C. maintaining this temperature 30 min, and filtering. The dried products obtained usually melt over a one degree range, between 129 and 132'C. Yields are 011 the order of 8 g, 7&80%. Less pure product call profitably be recrystallized from benzene before proceeding with the ninhydrin sequence.% If the reaction a t 70" is overheated or prolonged, increased quantities of hi-indone contaminate the high-temperature fractio~i of product. The yellow mother liquor obtained above is allowed to stand undisturbed at room temperature, in the dark, for a period of 1-7 days. The pale yellow to oliveyellow platelets which slowly separate are isolated by filtration, and air dried. The yield is 0.1-0.4 g of a product with a four to five degree melting point range near 200' (reported mp 208-2104). The main contaminant is indane-1,3-dione, which is removed by trituration with benzene to yield a product of high purity. Acknowledgmenl
The special assistance of Mr. M. Weinstein and X s s C. Goldrnan is greatly appreciated.
