YOSHIRO OGATAAND MASARUTSUCHIDA
2092 [CONTRIBUTION FROM
THE
DEPARTMENTO F
INDUSTRIAL
VOl. 81
CHEMISTRY, THE FACULTY O F ENGISEERING, KYOTOUNIVERSITY]
Kinetics of the Knoevenagel Condensation of Benzaldehydes with Diethyl Malonate B Y YOSHIRO OGATA AND I\fASARU
TSUCHIDA
RECEIVED & l A Y 22, 1958 The piperidine-catalyzed Knoevenagel reaction between diethyl malonate and benzaldehyde or ring-substituted benzaldehydes t o yield diethyl benzylidenemalonates has been studied kinetically a t 99.5" in kerosene solution. T h e rate of the formation of diethyl benzylidenemalonates and t h a t of the consumption of benzaldehydes has been followed by ultraviolet spectrophotometry. It was confirmed t h a t the reaction was accelerated by a small amount of organic acid (benzoic acid in the present ease), b u t retarded by a n excess. Both electron-attracting and releasing p-substituents retard t h e reaction. The rate was also measured in isopropyl alcohol, and the results were compared t o those in kerosene.
Many synthetic studies on the Knoevenagel and related reactions, have been reported, but there seem to be little data from the kinetic or mechanistic standpoint. It is generally accepted' that the reaction involves a preliminary removal of proton with bases from active methylene group followed by an attack of the carbanion on a carbonyl carbon atom. However, decisive kinetic support for the mechanism has scarcely been obtained. I t is known that amines salts of organic acids are better catalysts than free amines for this reaction.2 On the other hand, however, i t will be noted that piperidine alone is more satisfactory than piperidine acetate in acetic acid for the condensation of aldehydes with ethyl cyanoacetate.3 This rnysterious role of organic acids in the condensatior, has often been pointed out and some studies have been made of the condensation in the presence of a large amount of acid,? or with free malonic acid5 or its monoester.6 However, no rational explanation of this mechanism has yet been postulated. The present paper summarizes our results obtained on the kinetic study of the reaction between diethyl malonate and benzaldehydes yielding diethyl benzylidenemalonate in kerosene or isopropyl alcohol solution using both piperidine and benzoic acid as catalysts.
Anal. Calcd. for ClsHls04: C, 68.68; H, 6.92. Found: C, 68.77; H, 6.86. Commercial kerosene was treated several times with fuming sulfuric acid, washed with water and rectified. A fraction boiling between 240-280' was collected, which showed no appreciable absorption in the region 240-290 mp in a methanolic solution of the experimental concentrations. Typical Procedure for Rate Measurements.-As a n example, the rate measurements of piperidine-benzoic acidcatalyzed condensation of benzaldehyde with diethyl malonate is described below. Definite amounts of benzaldehyde, usually containing 0.1-0.2 wt. yo of benzoic acid, diethyl malonate, piperidine, benzoic acid and kerosene (20 ml.) were placed in a 100-ml. flask fitted with an outlet tube. T h e flask was imniersed in an oil-bath thermostated at 99.5 =t0.3", and shaken vigorously. At appropriate time intervals aliquots (0.2 ml.) were withdrawn and diluted to 10 ml. in a volumetric flask. From t h e solution, 0.5 ml. was taken out and again diluted t o 10 ml. with acidified methanol ( 5 rnl. of concentrated sulfuric acid in 1 1. of methanol), the optical densities of the rtwilting solution being measured a t appropriate wave lengths by a Heckman spectrophotometer, model D U , as shown in Table I . T h e percentage compositions of these solutions were determined in t h e same manncr as previously described' and the initial rate Va was evaluated graphically8 arid listed in Tables I1 and 111. The spectrophotometric measurements were carried out a t 245, 251 and 275 mp as slio~vnin Table I . Two differences of t h e optical TABLE I F O R RATE MEASUREMENTS. AND DIETHYL OPTICAL DENSITIES O F BESZALDEHYDES Ih' ~LCIDIC METHANOL ( 5 ML. OF BENZYLIDENEMALONATES CONCD.SULFURIC - ~ C I D "I N 1 L. OF METHANOI.~)
SPECTROPHOTOhfETRIC
DATA
ConcentraOptical densityb at tion, various wave lengths llaterials .bl X 1W 245mp 251 mp 275 mp Materials.-Unsubstitutetl and substituted benzalde0.806 0.080 0.802 384 hydes,'*8 diethyl malonate, piperidine, benzoic acid and CeHaCHO ,114 ,294 ,081 3.23 isopropyl alcohol used were of the best grade or preparcd by CeHaCH: C(COzCzH5)z 250 mp 265 mp 297..> nip standard methods and purified by either recrystallization or 0.872 0.210 0.608 19.2 vacuum distillations, until thc'r inelting or boiling points $-SO?CsIIdCHO ,062 ,098 ,233 agreed with those in the literature. All p-substituted diethyl $ - N ~ ? C ~ H I C: CI I( C ~ ? C ~ H S ) Z 2 . 3 4 2 t 0 m p 246 m p 278 mp benzylidenemalonates were synthesized by the condctmition of the corresponding benz:ildehyd ~-CIC~HICIIO 21.3 0.107 0.0972 0 . 0 0 3 8 lonatc using piperidine and benzoic fl-CICeIIdCH: C(COzCzHs)z 5.!46 ,183 ,200 ,810 ') Among them, diethyl p - c h l o r o l ~ e n z y l i t l ~ ~ ~ c ~ ~ ilias ~ i l ~bcvii iriatc -JJ mp 2130 mp 285 mp reported t o be an oily s u b s t a ~ i c ebut , ~ in our hands, the C O I I I - fi-CHIC6I34CIIO 250 0.110 0.105 0.014 pound, if maintained below 0' for threc \reeks, was hrouglit ,346 .8GO t o crystallization, 1n.p. 34-35". Diethyl p-rnethylheiizyl- ~ - C H ~ C ~ H I C I I : C ~ C O I C I I1~0 ~. 3) ~ 2 1 0,244 nip 217 mp 3 1 % mp idencnialonate, a new compound, \vas obtained i n colorless ~~~CII~)CGII~CHO ,551 0.IL'I 0.158 0.023 platcs melting a t 43-43.5'. $ - C H ~ O C ~ H ~ C H : C ( C O ~ C ? € 6~ ~12) Z ,147 .113 .728 ( 1 ) For example, see A . 12. Surrey, "Kame R e a c t i o n s in Orjirrnic I t \ V A S sllown tliat Beer's law w:is oheyed i l l these soluChemistry," Academic Press, I n c . , New U o r k , N. Y , 19,5i, p. l K 3 ; tions, :ind that these ci1)tic:tl densities were unaltered witli A. A . Frost and R . G. Pearson, "Kinetics and Riechanism," J o h n sinall variatioiis o f tlie acidity iif tlie s(Jlvcnt. E = log Wiley and Sons, Inc., New York, pi. Y . , 1953, p. 208. (IO!I ) = c r d = 0.5 E C . c This :wid considerably lowered ( 2 ) A. C. Cope, THISJOIJRNAI., 69, 5317 (19;37): R. K u h n , \V. opticxl densities of aldehydes. Badstubner and C. Grundmann, B e r . , 69, 98 (1930); R . I,. Shrincr and F. W . Neiiman, "Orjianic S y n t h e s e s , ' ' Coil. Val, 111, John W'iley densities, (E?45-E27s) zs. (E2SI-E:7S), were plotted anti thus and Sons, I n c . . New York, ?i. Y.. I!J5,5, p. 377; 11,J. Astle a n d U' C the :tinourits of benzaldehyde xnd diethyl benzylideneGergel, J . Orr Chem., 21, 493 (1956). ninlonnte were determined as a two-cornponcnt systcII1.' .~ (3) A . C. C o l w a n d C . h1. I I o f m a n n , THISJ O U R N A L , 6 3 , 34Sti ( 7 ) 1'. Ogata. 11,Tbuchida a n d Y . 'l'akaxl, t b i d . , 79, 33!l7 ( 1 0 5 7 1 . (19.1l i . sberfier, e
