A Kinetic and Mechanistic Study of the Alkaline Hydrolysis of Ethyl Acetoacetate by Acid-Base

Determination of the p& of the Ester

Rodrigo Paredes and Rogelio Ocampo Universidad del Valle, Apartado ABreo 25360, Cali, Colombia

The hydrogen bonded to the carbon between the two car- bonyls in p-ketocarbonyl compounds shows considerable acidity since the carbanion generated by its abstraction is stabilized bv hoth inductive and resonance effects ( I ) . Most of these ~ o ~ ~ o u n d s are sufficiently acidic that the derived carbanions can be generated in hydroxylic solvents such as water or alcohols, which have pK, values in the 15-20 range (2). The pK. values for carbon acids have been determined on the basis of the acid-base equilibrium:

R H t B - * R - + B H (1)

where R H is the carbon acid and B- is a suitable base. The pK, of ethyl acetoacetate can be evaluated on the

basis of the kinetics of the alkaline hvdrolvsis of the ester in which for each mole of OH- consumed-1 mol of ester is saponified. The kinetics of the reaction was studied by re- cording the decreasing pH of the reacting solution a t time intervals. For example for the reaction of 0.0100 M CH3COCH2C02Et with 0.0100 M KOH (Table 1) aplot of in [ester] versus time gave a straight line while a plot of 11 [ester] gave a curve, thus indicating first-order kinetics (3). When equal volumes of 0.0200 M CH3COCH2C02Et and KOH were mixed (time 0) to nroduce the solution in which lester],.,, = [OH-],",, = 0 . 0 1 0 d ~ , the starting pH was about 11.2 instead of the expected 12.00. This fact was interpreted as due to an initial very fast conversion of the ester &to its enolate, which rapidly establishes the ester-enolate equilib- rium before proceeding further in the reaction.

The starting ester and OH- concentrations ([esterlo and [OH-],,) can he evaluated hy extending the straight line of the plot of in [ester] versus time to intercept the in [ester] axis (time 0). When this was done a value of -6.34 was obtained for in [esterlo or in [OH-10, which correspond to startine ester or OH- concentrations of 0.00176 M. The starting enolate concentration [ e n ~ l a t e ] ~ is equal to 0.0100 - 0.00176 = 0.0082. The starting concentrations allow the de- termination of the pK, of the ester from eq 2.

[enolate], - [R-I = 3 - [ester],[OH-1, [RH][OH-] K .

(2)

The reported value for the pK. of ethyl acetoacetate is 10.7 (4). When the initial concentration of OH- used was slightly higher than that of the ester, the reaction remained first order as shown hv the fact that a plot of lu lesterl vs. time gaveastraight line whileaplot of l ia - hln bio - r h ( b - x) versus time eave a curve Wables 2 and 3). When the straight line plots o f h [ester] and in [OH-] versus time were extend- ed to intercept the in M axis, values corresponding to In [esterlo and in [OH-10 were obtained. From these values the

72 Journal of Chemical Education

Table 1. Experiment 1: 0.0100 M CH,COCH2C02Et and 0.0100 M KOH

Time is1 In [ester] In [OH-] l/[esterl

-6.40 -6.40 603 -6.49 -6.49 661 -6.59 -6.59 724 -6.68 -6.68 794 -6.77 -6.77 87 1 -6.86 -6.86 955 -6.95 -6.95 1047 -7.05 -7.05 1148 -7.09 -7.09 1202 -7.14 -7.14 1259

Table 2. Experlment2: 0.0100 M CHoCOCH2C02Et and 0.0105 M KOH

1 Ma-X) Time (s) pH In [ester] In [OH-] - In -- a-b s i b - ~ )

60 11.34 -6.36 -6.12 421 216 11.32 -6.44 -6.17 449 566 11.28 -6.57 -6.26 511 912 11.24 -6.69 -6.36 581

1253 11.20 -6.83 -6.45 660 1636 11.16 -6.96 -6.54 751 1803 11.14 -7.04 -6.59 802 2004 11.12 -7.11 -6.63 856

Table 9. Experlment 5: 0.0100 M CHSCOCH2CO2E1 and 0.0110 M KOH

1 Ma-d Time (s) pH In [ester] In [OH-] - h-- a-b afb-xi

Tabla 4. Calculated pKa's lor CH,COCH,CO,Et In Experiments 1,2, and 3 (25 OC)

Experiment [ester],., [OH-]mt In [esterlo in [OH-lo pKa

I 0,0100 0.0100 -6.34 -6.34 10.6 2 0.0100 0.0105 -6.36 -6.11 10.7 3 0.0100 0.0110 -6.50 -6.00 10.6

pK, of the ester was calculated by eq 2. Table 4 shows the pK, values obtained in the three experiments performed.

Simple esters such as ethyl propionate saponify by the B A ~ ~ mechanism showing second-order kinetics (5) since the rate-determinine sten is the formation of the tetrahedral negative intermidiat;. The kinetics of the alkaline hydroly- sis of ethvl nro~ionate bv acid-base ootentiometrv was also studied Ln border to contrast its behavior to that of ethyl acetoacetate. For initial concentrations of 0.241 M ethyl propionate and 0.0100 M OH- (Table 5) a plot of l l a - b In b(a - x)la(b - x) versus time gave astraight line while a plot of In [ester] versus time gave a curve as expected of the second-order kinetics (3).

Reruns This experiment illustrates the determination of the ki-

netic order for a simple reaction. Most esters show second- order kinetics in their alkaline hydrolysis since they follow the B A ~ ~ mechanism (5). Since the experimentally deter- mined kinetics for ethyl acetoacetate is first order, the ester must sanonifv bv a mechanism different from the classical ~ ~~~ .~~ . . B A ~ ~ mechanism. Three mechanisms have been proposed for the alkaline hvdrolvsis of ethvl acetoacetate which ac- " - count for the first-order kinetics and some other experimen- tal observations:

1. The Bw2 with an inert carbanion mechanism (6.7) involves the -~ -~~~

initial complete conversion of the ester into its enolate. Suhse- nuant. hvrlrnlvria of the enolnte resenerate low concentrations of 7---...,-...,... .. ..~. - ~ - ~ ~ ~ ~

ester and OH-. These species react, in the rate-determining step, to form the negative tetrahedral intermediate that Lead to the products.

2. The keteneElcB mechanism (8) also involves the initial complete conversion of the ester into its enolate. However, in this case the enolate, in the rate-determining step, expels an ethoxide ion to form a reactive intermediate ketene that hydrolyzes in the alka- line medium to generate the products.

3. The cycJic enol mechanism (9, 10) first involves the establish- ment of a base-catalyzed k e h n o l equilibrium. Next, rate-de- termining nucleophilic addition of water to the cyclic end takes place to form an intermediate dipolar ion whose breakdown lead to the products (see figure). The existence of cyclic enols with deloealized bonding has been reported in the literature (11-13).

For first-order kinetics to be followed by mechanisms 1 and 2. comnlete ionization of the ester to the enolate is required. -. - -~-~.~ ~ ~ ~ ~

The reported pK, value of 10.7 for ethyl acetoacetate (4) onlv allows 8W ionization a t the given initial concentrations ofekerand OH- ( 0 . 0 1 0 0 ~ ) . thusmaking these mechanisms douhtful. On the other hand mechanism 3 does not require complete ionization of the ester to the enolate for first-order kinetics t o be followed, thus making this mechanism more plausible.

Rate = k,[cyclic enol] [H,O]

[H,O] =constant k; = k3[H201

Rate = k; [cyclic enol]

But

[cyclic enol] = [ester]

Rate = k; K[esterl

The experiment also illustrates the determination of the pK. of an enolizable 8-ketoester on the basis of the initial ester- enolate eouilibrium. The exoeriment is m i t e easv and safe to perf or^. In addition to a pH meter kquippLd with an electrode caoable of readinrr nH's in the alkaline region, - . common eq;ipment, glassware, and reagents are utilized. We have used it with good results in a 3-h laboratory as a physical organic chem6try experiment for our advanced un- dergraduate chemistry students.

Experlmenlal A digital pH meter (Schat Gerate model CG 820) equipped with a

combined electrode (Sehat Gerate type H61) was used for the pH measurements in experiments 1,2, and 3. In experiment 4 a Metrion V Perkin Elmer Coleman 80 pH meter equipped with Thomas high pH electrodes was used. Redistilled water was used for the solutions.

Experiments 1. 2, and 3 Bvmeans of volumetric oioets 100.0 mL of 0.0200 M CHXOCHg-

C O ~ solution and 1lM.0 mi of the KOH solution of the &roori- ~~~~~~~~ -~ ~ - ~ ~ .. . ate roncentratiun (experiment 1.0.0200 M: experrment 2.0.U210 M: experiment 3.0.0220 MJ were poured into separate 200-ml. E r l ~ n - meyer flasks. The flasks were stoppered and kept at room tempera- ture (25 'C).

An empty 400-mL beaker equipped with a magnetic stirring bar was olaced on too of s mametie stirrer. When the reaction was to he mn.ihe DH ele$rndewas~ntroduced into the beaker. Then simulta- ~~~ ~~ ~ ~

neously the two ~olutionr were rapidly poured inw the beaker, the chronometer was started, nnd the magnetic stirring was turned on. pH readings were taken at time intervals. Tables 1,2, and 3 show the results

Experiment 4 An empty 200-mL hesker equipped with a magnetic stirring bar

was placed on tap of s ma~meticstirrer. Eighty milliliters of a 0.0103 M KOH solution was poured into the beaker. and the magnetic stirring was turned on. he pH electrodes were introduced into the heaker, and 2.02 g of ethyl propionate (0.0198 mol) was added raoidlv to the alkaline solution. As soon as the addition was com- ~ ~ . ~ ~ ~ ~ ~ , ~~ ~ ~ ~~ ~ ~

plete, the chronometer was started. pH readings werc taken nt time intervals. l'ahle 6 shows the results. The wltlme of r h ~ solution was measured at the end, arnuunting ro 82.3 ml..

Table 5. Expwlmenl1: 0.241 CHoCH,M2Et and 0.0100 M KOH

Ma-d L i n - Time (s) pH [ester] In [ester] a- b a(b- x)

0 12.0 0.241 -1.423 0 30 11.9 0.239 -1.431 0.96

120 11.5 0.234 -1.452 4.86 180 11.2 0.233 -1.457 7.83 240 11.0 0.232 -1.461 9.80

The cyclic end mechanism.

Volume 67 Number 1 Janualy 1990 73

Acknowledgment 5. R S ~ I, pp 1214123. 6. Pratt.R. F. ;Bmi~e,T.c. J.Am. Chem. Sac. 1910.92,5956-5964.

We acknowledge the financial support of COLCIENCIAS 7. ~ o b f a a . ~ , S.; ~ ( z d y , F. J. J . ~ m . C h m . Soe. 1969,91.5171-5173.

and the interest and advice of Zvi Rappoport. 8. Venkova Rao, G.; Bslakrishnam. M.: Venkataaubramanisn, N.; Subramanian. P. V.: Subramanian. V. Indian J. Chem. 1976; J4B, 465466.

9. Pandes. R.; Gil,J.Reu.Lolinoamar. Quim.,in press. Lltarature Cited 10. ~ ~ ~ d ~ ~ . R.; oeampo, R., submitted for pub~icatianr i n ~ m . ti^^^^^. quim.

Carey, F, A,: Sundberg, R, J, Aduoneed 2nd ed,: Plenum: New 11. Row1and.S. P.:Pearc~.L. Z.:Msck,C.H.: JanasenHJ. J. Cham.Soc. (B) 1968.40P

Ymk, 198k Part A. p 363. 406.

2. Ref I , p 371. 12. Lowray, A. H.: Gnngs, C.; D'Antonio, P.; Karle, J. J. Am. Chem. Sor. 1911.93.6399- 6403. 3. Bsrmw. G. M . P h ~ s i c d Ch=-trx 2nd. od.: MeGrsw-HiU: New York. 1 9 6 % ~ ~ 465- 13, n,M, S,SteticEiieefainOrg.nieChom raIry; Wiley:New 19S6;pp415-

4. Cram,D. J.findomenloL.ofCorbonion Chemi8try;Academic: New York. 1965;pp& 447

20.

74 Journal of Chemical Education