the micromile
edited by ARDEN P. ZIPP SUNY-Cortiand Conland. N Y 13045
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Editor's Note: One of the greatest deterrents to me adoption of microscale techniques for organic chemistry laboratory courses inmany institutionsis the hlphcost of microscale glassware. There are many exoBllments that can be carried out on a small scale using regular glassware as the following experiment demonstrates. infor""
criteria would be appreciated and should be sent to the editor of ttis column.
these
A One-Step Synthesis of Cinnamic Acids Using Malonic Acid: The Verley-Dobner Modification of the Knoevenagel Condensation Kenneth E. Kolb a n d Kurt W. Field Bradley Universihl Peoria, iL 61625 Paul F. S c h a t z University of Wisconsin Madison. WI 53706
A reaction that is very simple in both procedure and equipment needed (test tube) hut that has considerable synthetic and pedagogic value is the Verely1-Doebner2 modification of the Knoevensgel condensat i o n . V h e Knoevenagel reaction utilizes weak amine bases, such as piperidine, to form enolate anions derived from 8-dicarhonyl compounds as nucleophiles in the condensation with earhonyl compounds. The Verley-Doebner modification employs pyridine as solvent and catalyst and a cocatalyst such as 6'-alanine.' With this procedure malonic acid itself, rather than its diester, can he efficiently condensed with benzaldehyde ultimately affording t r o n s cinnamic acid. This procedure has been used at our institutions in the sophomore organic laboratory with yields of trans-cinnamic acid of 90%. The reaction illustrates several key concepts usually included in the first-year organic course: (1) the acidity of enolizable compounds containing two activating groups, (2) the stability and nucleophilicity of the enolate anion, (3) the ease of dehydration to extend conjugation, (4) the facile decarboaylation of a beta-keto-type adduct, and (5) the relevance of many of these concepts in biochemical processes.
A304
Journal of Chemical Education
Laboratory Procedure Into a 16-X 150-mm test tube weigh 1215 mg of 6'-alanine and 100 mg of benzaldehyde (about 5 drops). On weighing paper weigh out 250 mg of malonic acid, and add this along with 500 pL of pyridine and hoiling chip to the test tube. Cap the test tube with a rubber septum that has an open glass melting point capillary inserted through it with most of the capillary extending above the septum. The reaction mixture is refluxed for 90-110min a t arate such that the upper portion of the test tube serves as an air condenser. After reflux, the tube is air cooled for a minute or two, followed by immersion in an ice bath for P5 min. Addition of 1 mL of cone.HCL liberates the cinnamic acid, isolated as white crystals by reducedpressure filtration. Transfer of residual material from the test tube and washing is done with 2-3 mL of ice-cold water. Overnight drying is accomplished by leaving the crystals lowelv soread on a tared filter . DaDer . in the locker until the next period. Determine the melting point (13R°C),weight, and percent yield. Hecrystallizatim, if desired (normally not necessary), can be accomplished from hot water. This procedure works equally well with p-nitro-, m-nitro-,p-methoxy-, and 3,4-din-
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itrobenzaldehyde. For hydroxybenzaldehvdes. such as 3-methoxv-4-hvdroxv (vanill k l , 4-hydroxy, and 3,4~dih;drox).henznldehyde, satisfactory yields (50-80%) ran he obtained hy allowing the reaction mixture to stand a t room temperature for one to two weeks. Vanillin, for example, after standing for one or two weeks, affords the desired product in yields of 60% and SO%, respectively. These reactions are best done in a small Erlenmeyer that is not tightly stoppered since C02 is produced by the facile decarhoxylation. Attempts to speed up these reactions by vigorous reflux results in tar.
This experlment b adapted from papers presented at me 192nd ACS National Meeting. Anaheim. CA, 1986(CHED 0010)and the 194th ACS National Meeting, New Orleans. LA, 1987 (CHED 0105). Verley. BUN. Soc. Chlm. Fr. 11899. 21. 414. Doebner. Chem. Ber. IS00,33,2141. For a review, see Jones, G. In Organic Reactions: Adams, R.. Ed.; Wiiey: New York, 1967: pp 204-599. Cope, A. C. J. Am. Chem. Soc. 1937,59, 2327.
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