I
Roger Ketcham Pharmacv University of California Son Francisco
schoolof
I
The Amine Catalyzed Perkin Condensation A class project
During the past two years, we have experimented with a class project assignment during the second semester of organic chemistry instruction. In this exercise the students carry out the amine catalyzed Perkin condensations of substituted benzaldehydes with substituted phenylacetic acids to give m-phenyl-cis- and trans-cinnamic acid^.'.^.^ The following reactants have been used. Aldehydes: anisaldehyde, benzaldehyde, p-nitrobenzaldehyde; acids: p-methoxyphenylacetic acid, phenylacetic acid, p-nitrophenylacetic acid. Each student carries out one reaction, nine condensations being carried out by the class as a whole. Directions for preparation of the unsubstituted a-phenylcinnamic acids and a tabulation of conditions, yields, and melting points for all nine condensation reactions' are provided. We are now engaged in a continuing research program in which these a-phenylcinnamic acids are required intermediates so that they are found to be useful. Only one of these compounds is commercially available
' KETCHAM, R., AND JAMBOTKAR, D.,J . Org. Chem., 28,
1034
(1963).
FIESER,L. F.,"Experiments in Organic Chemistry,'' 3rd ed., D. C. Heath and Ca., Boaton, 1957, p. 181. GIMMERMAN, H. E., AND AHRAMJIAN, L., J . Am. Chem. Soe., 81,2086 (1959).
X
~
C
H
+
O
and several have just been reported in the literature. These facts seem to have generated a greater feeling of satisfaction among the students regarding this experiment than exists for many of those more commonly used. All nine condensation reactions proceed well. The low solubility of the dinitto acids and their salts leads to the greatest difficulty. Students who finish the laboratory work early and want to do an optional laboratory exercise have occasionally been assigned a "new" condensation. We have used p-chlorobenzaldehyde, ptolualdehyde, and o-nitrobenzaldehyde with satisfactory results. Separations of the isomeric acids are all quite good. If one of the acids is not cleanly separated from its isomer, the mixture is easily separated by redissolving it in alkali, followed by precipitation of the trans acid with acetic acid and the cis acid with hydrochloric acid. Methylene chloride is the most generally applicable solvent for extraction. Because of the difficulty in handling hot acetic acid solutions, the students are advised to omit the usual hot filtration in those crystallization procedures which require acetic acid. Normally, no insoluble material is observed in these solutions. The reaction conditions reported are the optimum ones obtained in the author's laboratory.
~ a s e ~
ccH,coi+
Y-IIZCO~H
JJ
X+CH=C,
COzH cis and trans Reflux time bin)
Mole ratio A/B
7, Yield Trans Cis
Melting point
X
Y
H OCHs H
H H OCHI
45 60
GO
1.6 1.6 1.6
68 57 72
11 12 19
1723 18+90 150-2
OCHa YOa H KO2 OCHj NOz
OCHs H NOz NO1 NOn OCHs
90 30 90 60 120 30
1.6 1.1 1.6 1.1 1.6 1.1
64 69 55 57 44 82
9.3 29 11 17 7 10
216-7 208-10 2214 269-71 235-7 191-2
Trans
("c)
Crystallization solventb Trans Cis
Extraction solvent
Cis
pH
138-9 120-2 1168 120-30 131-2 141-3 149-51 215-7 184-5 145-7
6.0 6.0 6.0
E
E-P Et E-P
EP EP E-P
6.2 4.5 4.5 4.0 5.5 5.5
M M M M
Ac A(
B-H B B Ac B B
M E
M
M
,
.
A< A* Ac A',
" For all condensations using pnitrophenylacetic acid, uae pyridine a8 the baae.
* Solvents: E = ether, P = petroleum ether (30-6O0C), A = acetic acid, H = h e m e , B = benzene, M = methylene chloride, E t = 95% ethsnol. Do not filterthese hot solutions.
Volume 41, Number 10, Odober 1964 / 565
