Enamine Reactions for the
S. D. Darling
Undergraduate Organic Laboratory
University of Southern California
Lor Angeles
I
A student water separator
Organic reactions which proceed with the formation of water often are facilitated if the water is removed in an azeotropic process. The use of a water separator in reactions such as enamine preparation or esterificationl illustrates the reaction progress to the student. The relatively high cost of a commercial Dean-Stark trap2 or the lack of glass working facilities for Pyrex brand glass may be responsible for the absence of this techni ue in many student laboratories. Although new &und glass kits are available for the undergraduate organic laboratory, most kits do not provide for this useful setup. A standard taper lab-kit3 developed in these laboratories has been used successfully in an arrangement which operates as a water separator. The versatile condenser which served previously as a fractionation column and simple distillation setup is readily converted into the water separator by the addi-
tion of a tuhe where the thermometer was formerly inserted (Figs. 1, 2).4 A 50-ml polypropylene centrifuge tuhe is warmed in a steam bath uniformly around the open end for a few moments. The tube is then forced over the tooled end of the condenser. When the plastic cools a tight seal is formed. The plastic tube is removed later with a pull and a twist. The condenser and flask are joined by a curved adapter and the apparatus is adjusted to provide an unobstructed flow of liquid and vapor (Fig. 1). An a11 glass apparatus is easily constructed if a condenser with a ground joint instead of the tooled end is used. A curved vacuum adapter, with the side arm closed by a rubber bulb, connects the condenser to the flask. The tapered tube shown (Fig. 2) is about 20 ml capacity and doubles a5 a small reaction Figure 3. tor funnel.
Wafer
sepam-
vessel or dislillatiou flask in other laboratory preparations. An even more efficient separator can be made from these setups if an internal funnel is inserted to conduct all of the condensate to the bottom of the tuhe. This is made from a piece of 6-mm glass tubing flared at one end and inserted into a piece of cork (Fig. ' P ~ R B A U O W. H , H., VLNSEI.OW, C. H., NELSON,K., AND SHRAWDER, E. J., J. CEEM.ED.,40,349(1963). *DEAN,E. W., AND STARK,D. D., Ind Eng Chem, 12, 2186
-- -
f\ i w n , >. A
Figure 1 . separator.
Polypropylene
woter
Figure 2. rator.
All-glar5 woter lepo-
'DARLINQ,S. D., AND BROWN,R. F.,J. CHEM.EDUC.42, 280 (1965). 'The author wishes to thank Professor 8. F. Darling of Lawrence University for the photographs of the apparatus. Sz~nsz~oncz, J. "Advances in Organic Chemistry, Methods and Results," (Editors: R. A. Raphael, E. C. Taylor, and H. Wynberg) Interscience Publishers, Inr., K e w York, 1963, Vol. 4, pp. 1-113.
Volume 43, Number 12, December 1966 / 665
Reaction Parameters for the Alkylation of 1 -Pyrrolidinocyclohexene Reartinn . .. -. ... ..
Solvent
Temperature
time (hr)
Benzyl chloride
Methanol
2 24
1-Butyl iodide
Methanol
Ethyl bromnacetate
Benzene
Acetic anhydride
Benzene
Methyl acrylate
Benzene
Acrylonitrile
Benzene
Methylvinyl ketone'
Benzene
Reflux Ambient Ambient Reflux Ambient Reflux Ambient Ambient Ambient Reflnx Ambient Reflux Ambient Reflux
Alkylating agent
A
Yield (%) 33 29
Re~orted yieid (%) 40
Reference (footnote)
7
. . G . . +
The yield of 2,6-dibenzylcyclohexanoneis 2.3%. Refluxed in toluene 19 br. Ethyl acrylate refluxed in dinxahe 3 hr. Refluxed in dioxane 12 hr. T h e reaction is hydrolyzed by a 0.5-hr reflux with aeetste buffer solution. a
b
\
3) which is wedged into the condenser throat. The assembly is pushed home with a cork borer or other tube and is easily withdrawn by the flared end of the glass tube. The literature on enamines suggests that the reaction time for enamine preparation and subsequent reaction is too long for most student laboratory se~sions.~ Most reaction times reported represent convenient increments for the experimenter and not minimal times. A typical reaction to prepare an enamine with the water separator is run by charging the flask with cyclohexanone and 10% excess pyrrolidine. The apparatus is assembled and beuzene added through the condenser to fill the trap and spill over into the flask. The benzene in the flask should about double the volume of the reactants but not fill the flask more than one-half full. After 1.5 hr of vigorous reflux a good yield of pyrrolidine enaminel is produced. Refluxing for an additional hour increases the yield slightly. The solvent is distilled from the enamine preparation and the excess m i n e removed by evacuating and heating the flask in a steam bath. The enamine is used crude or distilled under vacuum for the subsequent preparations. Typical reactions on 5 1 0 g of cyclohexanone have given 80% of distilled enamine. The enamine must he used during the same laboratory period unless provisions for storage under nitrogen at 0°C are available. a T h ~mnrnholine enamine .~~.~ - ~ -is. formed - ~ ~much - ~slower. After 2 hr reflux in toluene with p-toluenesulfonic acid catalyst the yield was 50% of distilled ensmine. 7 STORK, G. ETAL.,J Am Chem Sac, 85,207 (1963). R., AND PARISI,G., J Am Chem Sac, SEGRE,A,, VITERBO, 79,3503 (1957). ~
666
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lournal o f Chemical Education
The "Stork reaction,"' which utilizes enamines for alltylation, acylation, and Michael condensation permits the inclusion of these major organic reactions in a student laboratory without the use of strong bases. Examples of the above reaction.- cau be carried out in refluxing solvents such as methanol or benzene. An inert atmosphere is not required but a drying tube should be used. If the preparation of the enamine has consumed most of the laboratory period, the alkylation reactions may still be carried out by mixing the reagents in an Erlenmeyer flask. The flask is stoppered and let stand for a day or until convenient. If the air in the flask is displaced with nitrogen before it is sealed the reaction mixture will be less colored when it is worked up. I n either method the euamine is mixed with solvent to give a 30% solut,ion (w/v) and the alkylating agent is added rapidly to the solution. The work-up of the reaction requires the addition of excess water and boiling for 0.5 hr. Additional water is added to cause separation of the product. Details on the work-up and characterization of many products may he obtained from the literature.' Although some yields are moderate the products isolated are relatively pure because .V-alkylated product is water-soluble and thus eliminated in the work-up. Alltylation of the enamine with 1-but,yl iodide or aerylonitrile is not sufficiently completed in the short reaction time. Hydrolysis of the reaction regenerates cyclohexanone which must be separated from the product by careful distillation. A summary of the conditions for reaction of I-pyrrolidinocyclohexene and the yield of product, is given in the accompanying table.
