The Modern Student loboratory Ph~sical-OrganicChemistry
Kinetic Demonstration of Chemospecific Reactions Involving Salicylate Esters and Amines An Experiment for Advanced Undergraduate/Postgraduate Students Nordin H. Lajis and Mohammad Niyaz Khan Universiti Pertanian Malaysia, 43400 UPM, Serdang, Selangor Darul Ehsan, Malaysia
The mninolysis of ionized phenyl and methyl salicylates involvri; inrram~)leculnreeneral base catnlvsis. The reactants (ionized salicylateesters) absorb strongly, whereas the ~ r o d u c t s(ionized ~ h e n o lN,N-dimethvlsaliwlamide , and'salicylic acid) do not absorb a t 350 nm: Molar absorptivity of the product, ionized N-methylsalicylamide, is about 2-3-fold smaller than those of reactants a t 350 nm. The reaction rates a t pH 2 11 can be measured spectrophotometrically by monitoring the decrease in the absorption a t 350 nm. General acid-base (GA-GB) catalyses have been suggested as an essential factor in several enzyme-catalyzed Feactions (I).An experiment based on synthetic demonstration of chemo- and regiospecificity in the reduction of carvone has been described (2). . . Recentlv. " , we found that phenyl salicylate 1 was highly reactive towards both primary and secondary amines in a n alkaline medium (3). Methyl salicylate 2 was significantly reactive towards primary amines but totally nonreactive towards secondary amines of comparable basicity i n a n alkaline medium (3-6). ~~~
~
~
~~
Equipment double-beam W-vis or single-beamvisible spectrophotameter '3-mL cuvette (silica or ordinary grade) I-, 2-, 5-, and 10-mLgraduated pipets (or syringes) 100-mLconical flask with stopper 100-mLvolumetric flask stopwatch thermostated water bath (or equivalent)
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Preparation of Solutions Due to the low water solubility and the problem of facile transesterification of phenyl salicylate in a n alkaline alcothe stock solution (0.02 M) of this ester holic solution (7,8), is best prepared i n acetonitrile. The stock solution of methyl salicylate is prepared in methanol. However, i t may also be prepared in acetonitrile. All other stock solutions are prepared in distilled water. Kinetic Measurements
Experimental Careful: The recordingafAObs versus t should be exact. Firstorder rate constants kobs (= ko) for hydrolysis of 1and 2 are independent of [OH-] within about the range of 0.001-0.07 M, and first-order rate constants are not affectedby the change in the initial concentrations of the reactants (1or 2). Thus, a slight error in the initial concentrations of NaOH, KOH., 1., or 2 will not affect values of k ""e . ~ . . The DHof the reaction mixture must be greater than or about 11. .Caution: The reaction vessel should he kept stoppered. Amines are irritant and corrosive. Appropriate care should be exercised when handling 1.5 M amine amd 2.5 M NaOH solutions. Safety ~. ~ l echemical-resistant s, gloves, and lab.m .. oratory coat should be worn when preparing and carrying out the experiment. Chemicals phrn,vl .inllrylate 10.02M in aw~onitrilc, mrrhyl snlieylarr about 0.112hl in methanul methvlammunium chlorldr 1 . 5 hl a n d 0.25 .M in wsrrr, dimethylammonium chloride (1.5 M and 0.25 M in water1 trimethylammonium chloride (1.5 M in water) sodium chloride or potassium chloride (2.5 M in water) sodium hydroxide or potassium hydroxide (2.5 M and 0.25 M in water) acetanitrile methanol
A264
Journal of Chemical Education
For a typical kinetic run, prepare the reaction mixture (24.75 mL) by mixing the appropriate amounts of 0.25 M amhe hydrochloride salt solution 2.5 M or 0.25 M potassium hydroxide or sodium hydroxide (The amount of KOH or NaOH should be enoueh to neutralize completely the mine hydrochloride salt and produce in excess of about 0.02 M KOH or NaOH in the reaction mixture.) 2.5 M potassium chloride or sodium chloride (to maintain the ionic strength at 1.0 M)
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With a Thermostatic Cell The solution is then equilibrated for about 5-10 min a t 30 'C using a thermostatic water bath. While thermal equilibrium is being established, make sure that the spectrophotometer is ready for use a t a constant wavelength of 350 nm. Initiate the reaction by injecting 0.25 mL of 0.02 M salicylate ester solution (prepared in acetonitrile for 1 and (Continuedon page A266)
The Modern Student laboratory Nonlinear Least-Squares (NLS) Methods The integrated form of the rate equation for a first-order reaction is given by C= ~ ~ ~ ~ (1) b
Table 1. The Values of the Calculated Parameters from eq 1
~
'
where C and C, represent the concentration of reactant at time t = t and t = 0, respectively. In the kinetic measurements using UV-vis absorption spectroscopy, C = Mobs-A..Xeapp and C, = (A, - A_)/%, where A, represents the absorbance of the reaction mixture at t = 0. In terms of the absorbance values, eq 1may be rearranged to give eq 2
Total concentration of nucieophiies. Tphenyl saii~yiate]~ = 2 . 0 10 ~ M: 1350 nrn; 1.0 M ionic strength: 1% (vlv) CH3CN into the reaction mixture and 30 'C. The values ko have been found to lie between 3.60 x 104and 4.10 x 1 0 ~ s " . d ~ r limits ~ r are standard deviations. e[Methyl saii~ylate]~ = 2.13 x lod M; h = 350 nm; 1.0 M ionic strength; 1% (viv) CH30H into the reanion mixture and 30 'C.
methanol for 2), using a l-mL blowout pipet or syringe in the temperature-equilibrated reaction mixture. Shake the reaction mixture thoroughly. Start the stopwatch as soon as part of the phenyl or methyl salicylate solution is added to the reaction mixture. Quickly withdraw an aliquot of nearly 2.5 mL from the reaction mixture, transfer it to the 3-mL cuvette, and place it in the thermostated cell compartment of the spedmphotometer. Record the absorbance reading (Aobs) at 350 nm and at time intervals that provide a decrease in A of nearly 0.05 absorbance units. Continue rewrdingAab versus time (t) until 10-15 data ~ o i n t are s obtained. Rewrd the last data point at time 11 = I - , where no detectable change inA.a, is observed within about a 30-min time interval. The absorbance at t, is represented as Am. Without a Thermostatic Cell When the spectrophotometer is not equipped with a thermostatic cell compartment unit, withdraw the aliquot of approximately 2.5 mL periodically from the reaction mixture, and transfer it quickly to the cuvette. Place it in the cell compartment of the spectrophotometer,and rewrd the absorbance a t 350 nm. The time lag between the withdrawal of an aliquot and the recordine of absorbance should always be 5 30 s. However, for a si&ificantly fast reaction, usea single aliquot to get more than one data point within a period of 5 60 s. Any amp in the temperature during this period may be considered negligible if the experimental temperature (30 'C) is not significantly different from the ambient temperature. Kinetic Data Analysis The wncentrations of salicylate esters were more than 25 times smaller than those of amines. Under these wnditions, the aminolysis of salicylate esters obeyed the firstorder rate law. The observed data (observed absorbance versus time) may be used to calculate the observed pseudofirst-order rate constant (kOb.)using either of the following methods. A266
Journal of Chemical Education
Aobs= c
~
E +A_ ~
~
~(2) ~
where Co~app =Ao-A- and E,,, represents the apparent molar absorptivity. Eapp, an.d G. The unknown parameters, k,. were calculated from eq 2 using the nonlmear least-squares technique, and these values are summarized in Table 1.A reasonably good fit of the observed data to eq 2 is evident from the standard deviations associated with the calculated parameters (Table 1). Graphical Method If microcomputer as well as nonlinear least-squares computer programs are not easily accessible, then the slopes of the wnventional plots of in (A,& - AJ versus t may be used to calculate the rate constant ( k , d This technique was also used to calculate hob,from the observed data, and the results obtained are shown in Table 2. For slow reactions, Table 2. Obsewed Pseudo-First-OrderRate Constants (. k d. Calculated from the Plots of In ( A o ~ s -A,) vs. t
Ester
Nucleophile
[NUIT
lo416bs
s.j
M
0p.t t= 50 min: [KOH] = 0.02 M: pH = 12.10. 'A- = 0.007. t= 28 min; [KOH] = 0.02 M: pH = 12.10. ' A= 0.W8. 'nt t = 146 min; [KOH] = 0.02 M: pH = 11.20 S -~ L = 0.224. -Qt t = 153 to480 min; [KOH] =O.O5M; pH = 12.11. ' A= 0.018. i ~t =t 480 min; [KOH] = 0.05 M; pH = 12.00. 'A. = 0.008. 'AI t= 480 min; [KOH] =0.02 M; pH = 11.19 ~
~
bobs
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~
Physical-Organic Chemistry such as reactions of dimethylamine with 1 and trimethylamine with 1 and 2, the values ofA.. may be obtained by warming the reaction mixture a t about 70 'C for a period during whichA_ values level off. Results and Discussion The simple aminolysis of salicylate esters may be given by
Table 3. Apparent Nucleophilic Second-Order Rate Constants (kn) Ester 1
2
where k, represents a nucleophilic second-order rate constant. The observed pseudo-first-order rate constants (k,b)obtained for the cleavage of ionized 1and 2 in the presence of methyl-, dimethyl-, and trimethylamine are summarized in Tables 1and 2. .,k = k, + k"[R,R*NHI where [R1R2NH]represents the concentration of primary or secondary amine nucleophile; and k, is the rate constant for hydrolysis. The nucleophilic second-order rate constants (k.) are shown in Table 3, showing that the trimethylamine did not exhibit anv detectable nucleo~hilicreactivity towards 1 and 2. I)imethyiamine reveuled a significantly high nudeophilir reuctivity wwards 1, but such reactivity could not ~
~
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plda
Nucleophile CH3NHz (CH~ZNH (CH3)3N CH3NHz (CH3)zNH
lo4knb
10.85
1755.0
11.05
5240.0
9.95 10.85 11.05
KXhlnN . -
