Anal. Chem. 1985, 57,2197-2204
2197
Characterization of a Chemically Bonded Stationary Phase with Kinetics in a Liquid Chromatographic Reactor Alexander H. T. Chu and Stanley H. Langer* Department of Chemical Engineering, University of Wisconsin-Madison,
Llquld chromatographiccolumns are shown to be operable as chemical reactors for lnvestlgatlng solute-stationary phase lnteractlons In reversed-phase systems. The klnetlcs of several organlc base-catalyzed esterlflcatlon reactlons of tetrachloroterephthaloyl chloride (TCTPCI,) and Its half ester 4-(methoxycarbonyl)-2,3,5,6-tetrachlorobenzoyl chlorlde were studled In a llquld chromatographlc reactor (LCR). The comparison of on-column rate constants In the methanol moblle phase and the methanol solvated octadecylsliane bonded statlonary phase illustrates an addltlonai method for obtalnlng lnfonnatlon about the character and composltlon of chemically bonded chromatographicsystems. These klnetlc results favor a generallzed statlonary phase model whlch Involves methanol molecules assoclated wRh the hydrocarbon ligands of the support surface. Devlations from values for an ldeallzed model suggest that there are associated methanol concentratlon varlatlons at the moblle-statlonary phase boundary and the slilca surface, some of whlch may be due to geometric and sterlc effects.
The advantages of high-performance liquid chromatography (HPLC), including high selectivity, high column efficiency, and the capacity for analyzing heat-sensitive and nonvolatile compounds, have led to its wide adaptation in many areas, particularly in biochemical and environmental studies. Compared with the multifold applications of gas chromatographic techniques to physicochemical measurements, ranging from the studies of solution thermodynamics ( 1 4 ) to catalytic processes (1-6) , applications of HPLC to physicochemical measurements have been limited (7,8). Although interesting applications of liquid chromatographic systems to reaction studies have been described (9-11), use of the liquid chromatographic column as a combined chemical reactor and separation device initially has involved emphasis on liquidsolid chromatographic effects on equilibria (12-14) or band broadening (15). The “chromatographic reactor” concept in which the chromatographic column is used for simultaneous reaction and separation of chemical species on a column has been mainly developed for gas chromatographic reactor (GCR) applications to date (16-20). The potentially important advantages over conventional static or flow reactors which have drawn interest heretofore to chromatographic reactor developments include (1)rapidity and ease of obtaining considerable information for kinetic studies, (2) the elimination of thermodynamic limitations on conversion with the separation of products so that reverse reaction is limited, (3) a small sample size requirement and a recorded chromatogram without sample transfer, and (4)the separation of any impurities, inhibitors, or stabilizers in the reactant mixture from the reactant in the course of column passage, so that unwanted interference is minimized. The unique features of the chromatographic reactor concept combined with those of liquid chromatography stimulated this further investigation of the application of the liquid chromatographic reactor (LCR) for obtaining information about 0003-2700/85/0357-2197$01.50/0
Madison, Wisconsin 53706
the stationary phase as well as for chemical kinetic studies. Beyond the determination of rate constants, the use of chromatographic techniques in kinetic studies has been appealing because reacting species and intermediates involved in complex reactions can be characterized in the course of study by their chromatographic retention characteristics (17, 18). Further understanding of reactions in liquid chromatographic columns also could be of significant help to investigators who encounter unrecognized problems from reaction in the course of analysis. Earlier, columns with chemically bonded liquid chromatographic packings were applied as chemical reactors for the study of the base-catalyzed esterification reactions of tetrachloroterephthaloyl chloride (TCTPC12 or 2,3,5,6-tetrachloro-1,4-benzenedicarbonyldichloride) to demonstrate the potential of this HPLC application (21). Here we describe some possibilities for using the TCTPClz reactant molecule as a probe for exploring the composition of a surface-bonded stationary phase. A number of spectroscopic techniques have been employed for this purpose earlier, including NMR (22-25), fluorescence (26,27), and infrared (28-30), as well as absorption bandwidth (31). The understanding of rate processes in the chemically bonded stationary phase is of further interest because it can lead to a new approach to obtaining special information about the stationary phase through on-column reaction kinetics. Since there can be significant differences in the solvent nature of the stationary and mobile phases, e.g., polarity and molecular structure, it is of interest to compare solvent effects on chemical reaction rates in the chromatographic column. An earlier study using 13CFT-NMR has shown a significant alcohol solvation effect associated with the complex reaction intermediate, N-(tetrachloroterephthaloy1)pyridinium ion (see eq 19), since it did not form in neat, less polar tetrahydrofuran solvent within a time frame of interest (1day). Rate data in methanol in a static batch reactor have also been obtained using conventional HPLC analysis (21, 32). Here, the results from a chromatographic reactor study are compared with such static kinetic data to extract rate parameters in the bonded stationary phase. This is of interest because of the previously mentioned possibility of obtaining a better understanding of the character of the stationary phase, even though the dominant role in RPLC separations often has been attributed to hydrophobic or solvophobic effects in the mobile phase (33-37).
In investigation of the association of a methanol “pseudolayer” with the bonded hydrocarbon ligands in liquid chromatography, an adsorption isotherm experiment was used to measure the total methanol associated with the stationary phase for our Altex Ultrasphere-ODS columns. From these experimental data, with other kinetic information, the predicted rate constant values for various stationary phase models can be calculated. For first-order or pseudo-first-order reactions occurring in both the mobile and stationary phases, an “apparent” or composite rate constant for the column is measured by using the pulse-elution liquid chromatograms obtained at different mobile phase flow rates. After the ap0 1985 American Chemical Society
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ANALYTICAL CHEMISTRY, VOL. 57, NO. 12, OCTOBER 1985
propriate reaction rate in the mobile phase is subtracted from the “apparent” rate constant, a stationary phase rate constant can be calculated and compared with that estimated on the basis of several models to gain information on the composition of the chemically derivatized phase. The kinetic results reported here support a generalized stationary phase model which involves the methanol “pseudolayer” associated with bound hydrocarbon moieties and the silica surface.
THEORY OF LIQUID CHROMATOGRAPHIC REACTORS During the development of chromatographic reactor concepts, a variety of approaches have been employed to model behavior involving simultaneous separation and reaction processes. Here mathematical equations are derived for evaluating rate parameters for the first-order reactions in the chemically bonded liquid chromatographic reactor (LCR). In treating the reversed-phase liquid chromatographic reactor, we confine ourselves to the following conditions: (1)Organic solvent is used throughout as the mobile phase without water; the bonded alkyl chains are usually solvated in such organic solvents and significant amounts of solvent may be extracted into the stationary phase. Studies of the dependence of the bonded alkyl configuration, retention, and selectivity on the mobile phase solvent composition are not emphasized; they have been reviewed elsewhere in the absence of chemical reaction (35-37). (2) Reaction is assumed to occur under isothermal conditions; the dependence of bonded alkyl structure and retention mechanism on temperature which has been investigated by Gilpin and co-workers (38, 39) is not discussed here. The column can be maintained isothermal since solution and reaction heat effects are negligible with only a small amount of reactant introduced into the system. The heat generated by the viscous dissipation due to the high-pressure drop through the packed bed (40,41) has recently been reported as insignificant during operation at relatively slow flow rates (below 1.0 mL/min or 1000 psi); thus, the reactor system can be assumed isothermal at the thermostated temperature. The liquid chromatographic reactor here is one in whch solute reactant or reaction mixture is introduced as a pulse onto the column where it is converted to products in the course of passage through the column. For an isothermal and homogeneous chromatographic reactor column, a complete material balance on a differential section of the liquid chromatographic column at position x and time t can be represented by (16, 17)
with initial and boundary conditions
Cm(x,O)= C,(x,O) = 0
at t = 0
(3)
Cm(O,t) = @ ( t ) a t x = 0 (4) where $(t)is the reactant input function at the column inlet. Considering first-order or “pseudo”-first-order reactions in both the mobile and the stationary phases
With equilibrium distribution between two phases, i.e., C, = KACm
Solving this equation by Laplace transform gives the reactant concentration in the mobile phase as (16, 17)
Cm(x,t) = @(t- aAt,) exp(-PAtm)
(7)
where “A
PA
=
=
(fm
(fmkm
+ fsKA)/fm
(8)
+ fsksKA)/fm
(9)
Since the capacity factor k i = fsKA/fmequals the ratio of the reactant residence time in the stationary phase to that in the mobile phase, klA = ts/tm,then Cm(X,
t ) = @ [ -t ~( t , + t,)I exp(-kmtm
kt,) (10)
where t R is total residence time of reactant. This result parallels that of Roginskii and Rozental (42) except that volume fractions, f, and f,, are used as characteristic chromatographic bed parameters instead of the void fraction, E term, of adsorptive reactors. The conversion XA, of the reactant A at the column exit can be expressed as
JmC,(X,t) d t XA=1-
S, cm(o,t) d t
= 1 - exp(-kmtm - hst,)
(11)
where x is the column length and Wout/Win
where C, f, a, and r are reactant concent.ration, volume fraction, diffusion coefficient, and reaction rate for the designated phase ( m , mobile; s, stationary); u ( x ) is the linear velocity of the mobile phase. The terms on the right-hand side are associated with longitudinal diffusion, convection, and reaction, respectively. Volume fractions of each phase, f m and f,, are employed here instead of the porosity or the void volume fraction of the column, E , because of the significance of the phase ratio (6= f,/fm) in reversed-phase liquid chromatographic operation. A generalized “sorption” term is used to designate either the dynamic partition or adsorption process which operates across the interface boundary; either or both processes may be involved in the retention mechanism. For a reversed-phase LCR with negligible diffusion and constant flow eq 1 can be simplified so that
= exP(-hmtm - kats)
(12)
With the addition of an inert reference material (peak) to the reaction mixture, and a standard treatment for extracting the rate constants from the experimental data (16,17),then
where AR and AI are the peak areas of reactant and inert standard, WR,inand WI are the weights of inlet reactant and inert material, SRand SIare the detector sensitivity factors for reactant and inert material (Si= Wi/Ai), respectively, and kappis the apparent rate constant which is
ANALYTICAL CHEMISTRY, VOL. 57, NO. 12, OCTOBER 1985
With the logarithm of the area ratio, ARIAI, plotted against the retention time of reactant in the system, kappis obtained directly from the slope. With the ratio t,/t, constant for a particular chromatographic column, k, and k, cannot be decoupled by simply varying the flow rate. Efforts have been mhde to extract one rate constant by using a known value of the other (43),or assuming one is negligible (21). Rate data have been estimated simultaneously by changing the percentage loadings of stationary liquid phase in gas chromatographic columns (18,M). Then, apparent rate constants, Kapp, are plotted against the resident time ratio, t,/t,, so that k, and K, can be determined from the intercept and the slope of a straight line.
EXPERIMENTAL SECTION Liquid Chromatographic Reactor System. The chromatographic equipment employed in this kinetic study was essentially the standard HPLC type of most laboratories; the analytical procedures are standard and comparable to those for routine analysis. Simplicity and compatibility with ordinary HPLC systems make the liquid chromatogrpahic reactor attractive for appropriate physicochemical applications. The liquid chromatographic system of our laboratory employs two Altex Ultrasphere-ODS HPLC columns in series connected with a l/z in. length of 1/16 in. tubing (0.01 in. i.d.). Two columns were used to provide longer residence times for the relatively slow esterification reactions to proceed. With this arrangement, appreciable conversions are achieved for better kinetic measurements. The colunns, 25 cm long, 4.6 mm i.d., contained 3.2 g of 5-wrn particles with a surface area of 200 m2/g and an average pore diameter of 80 A; they were thennostated by circulating water for reaction temperature control. The bonded stationary phase was a monomolecular layer of octadecyldimethylsilane, with trimethylsilyl end capping. The surface coverage of octadecyldimethylsilane is reported as 3.0 wmol/m2 and the packing material is 12% by weight carbon (45). The mobile phase solvent was pumped through the column with a Waters 6000A solvent delivery system. The reaction sample solutions were introduced to the solvent stream with a Beckman Series 210, four-port sample valve with a 20-wL sample loop. The effluent passed through a Perkin-Elmer LC-55 variable wavelength spectrophotometer detector adjusted at a detection wavelength of 223 nm. The peaks were timed and recorded with a Spectra-Physics SP4000 data processor as well as a Honeywell Electronik 194 recorder. The flow rate was checked with a vertical, 1-mL pipet, graduated in 0.01-mL increments; a two-way valve permitted diversion of the outlet stream through the pipet for flow measurement. The time between graduations was measured with a stopwatch. Reagents and Solvents. Distilled-in-Glass grade methanol was obtained from Burdick & Jackson Laboratories, Inc. (Muskegan, MI). The methanol solvent used as the HPLC mobile phase was further filtered through a Fluoropore filter (Millipore Corp., Bedford, MA) with a 0.5-~mpore size. Pyridine and 4-picoline catalysts purchased from Aldrich Chemical Co. (Miwaukee, WI) were dried over 4-A molecular sieves for 1 or 2 days. HPLC grade tetrahydrofuran-UV (Burdick and Jackson Labs) (THF) was dried over 5-A molecular sieves for 2-7 days. Commercial tetrachloroterephthaloyl chloride (TCTPC12), mp 146.5-148 "C, was recrystallized in our laboratories (46) and 4-(methoxycarbonyl)-2,3,5,6-tetrachlorobenzoyl chloride (Me,Cl-TCTP), mp 106-107 "C, was isolated as an intermediate by preparative liquid chromatography in the course of methanolysis of tetrachloroterephthaloyl chloride. A total of eight sets of experimental runs (a 23 factorial design) were performed to obtain a wide spectrum of kinetic results for analysis. The mobile phases consisted of a relatively dilute base catalyst in a methanol-tetrahydrofuran solution which was 0.25 M in (THF). The base concentrations were (1)pyridine 0.0050 M at 25 "C, (2) pyridine 0.0050 M at 35 "C, (3) pyridine 0.0075 M at 25" C, (4) pyridine 0.0075 M at 35 "C, (5) 4-picoline 0.006 15 M at 25 "C, (6) 4-picoline 0.006 15 M at 35 "C, (7) 4-picoline 0.0082
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M at 25 "C, and (8) 4-picoline 0.0082 M at 35 "C. The injections were 20 KLof a methanol solution 0.0003 M in TCTPC12reactant, 0.01 M in inert standard, and approximately 0.25 M in THF. The TCTPClz concentration was low enough to ensure pseudo-first-order kinetics, linear sorption isotherm, and minimal reaction heat effect. Either UV-sensitive nphenylheptane or n-phenyloctane (Aldrich Chemical) was utilized as an internal standard for the pyridine or 4-picoline catalyzed reaction, respectively. Tetrahydrofuran, used to aid the dissolution of TCTPC12crystals in the reaction sample mixtures, was present at such a low level that no spectrophotometric interference or special solvent effect was observed on the esterification kinetics (32). Batch Reactor Studies of Reaction Kinetics in Methanol/Octane. The organic base-catalyzed reaction rates of TCTPC12in bulk methanol solvent were measured earlier and described elsewhere (32). For the Me,Cl-TCTP half ester, a similar procedure was followed using HPLC for analysis for kinetic data. For reaction kinetic studies in the mixed methanol-octane solution, about 0.01 g of the TCTPC12crystals was weighed and dissolved in 9 mL of THF in a vial. Octane was chosen to study the hydrocarbon dilution effect on the rate of pyridinium salt formation. The solvent dilution effect should be comparable to octadecane for the batch kinetic studies especially since hydrocarbons are not conducive to reaction (32). Octadecane per se could not be used as a diluent since it is a solid (mp 30 "C) at room temperature and not miscible with methanol. Even with octane, it was necessary to use some tetrahydrofuran as a diluent for solvent miscibility. In other work (32),we found that THF did not significantly affect the esterification kinetics in methanol. A solution was prepared in a reaction flask from a total of 60 mL of methanol (containing the required amount of base catalyst) and 35 mL of octane thermostated at the desired temperature to correspond to the approximate hypothetical composition of the methanol/octadecylsilane stationary phase of model I1 (vide infra). The TCTPC12/THF solution was added to the reaction flask to initiate the base-catalyzed reaction. Samples of the reaction mixture were withdrawn periodically and introduced into the liquid chromatographic system with a methanol mobile phase for batch reactor kinetic analysis. Rate constants were obtained by measuring the areas of the decreasing reactant peaks at various reaction times. Rates were approximately proportional to the methanol concentration (v/v) (58%) in the mixture. For the 4-picoline (0.0099 M) catalyzed batch reaction at 35 "C, the s-l, about 57% of that measured rate constant was 7.56 X 5-l); for the 0.012 M obtained in bulk methanol (1.32 X pyridine catalyst concentration, the measured value was 3.60 x 8 ,about 60% of that in methanol (5.98 X 10" s-l); for the 4-picoline (0.0099 M) at 25 "C, the rate constant in the methanol/octane mixture (4.3 X lo4 s-') was 66% of that in methanol (6.5 x 10-4 9-11.
RESULTS AND DISCUSSION Determination of the Methanol Volume Extracted in the Stationary Phase by Gas Chromatography. The experimental procedure of Westerlund and Theodorsen (47), McCormick and Karger (48), and Yonker et al. (49,50) was modified to determine the total amount of methanol in the chromatographic system, VT,M,OH,at 25 and 35 "C. The amount of methanol associated with the stationary phase, V S , M ~ O H ,can then be calculated according to VS,MeOH
=
VT,MeOH
- (vm +
Ve,)M%
(15)
where Vm is the column mobile phase volume plus dead volumes between the injection valve and column inlet and between the column outlet and detector cell (2.25 mL) determined by the homologous series method (49,50),V,, is the extracolumn dead volume (0.1 mL) determined from connecting tubing between pump head and injection valve, and M% is the methanol composition in eluent (=loo%). Six standard solutions containing 1.0,2.0, 3.0,4.0, 5.0, and 6.0 mL of HPLC-grade methanol, respectively, in a 50-mL volumetric flask were prepared with 2.0 mL of 1-butanol as an internal standard in dioxane (HPLC grade). 2-Propanol
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and 1-propanol, suggested by other investigators, were not suitable internal standards since both showed tailing or unresolved peaks with methanol in either Carbowax 2000 or a Silicone DC550 gas chromatographic column. A Carle Carbowax 2000 column was employed for analysis with a thermal conductivity detector. For each run the Altex Ultrasphere-ODS column was equilibrated with the methanol mobile phase at specified temperature (25 or 35 “C) for a t least an hour. The mobile phase flow rate was set at 1.0 mL/min. The column was then flushed with about 47 mL of HPLC-grade dioxane a t 1.2 mL/min or 1.8 mL/min into a 50-mL volumetric flask containing 2.0 mL of 1-butanol as an internal standard. The contents of the flask was brought to the 50-mL volume with dioxane and then mixed vigorously. About 3 mL of solution was introduced into a 5-mL vial for sample analysis. An SGE l.O-wL syringe was used to inject 0.10 pL of sample into the Carle Carbowax 2000 gas chromatographic column (at 80 “C and 22 mL/min He) to obtain the peak area ratio of methanol to 1-butanol. A second 50-mL batch was collected for checking for the presence of residual methanol in the column, but it contained no detectable methanol. This procedure was repeated a t different flushing rates a t two different temperatures. A total of six sample solutions were collected and analyzed: 25-1, 25-11, 35-1, 35-11, 35-111, and 35-IV. For 25 “C samples, the area ratios of methanol vs. 1-butanol were 1.77 f 0.11, equivalent to 0.56 f 0.07 mL in the stationary phase. For 35 “C samples, the area ratios were measured at 1.81 f 0.06 from 15 data points, which is equivalent to 0.64 f 0.05 mL of methanol incorporated in the stationary phase. Among these data, no significant difference between duplicate samples or injections was observed. This study indicated that one molecule of bonded octadecyldimethylsilane ligand binds about seven to eight molecules of methanol within the underlying derivatized silica matrix, a value smaller than that (11.2 mol of MeOH/mol of ODs) calculated from Burke et al. experiment (49,50)with a 10-wm LiChrosorb RP18 column. Furthermore, it is possible that some methanol might associate with the silica surface as well as with the immobilized ClS chains as suggested in previous work (47-50). Although it is still unclear how such a monomolecular methanol layer is combined with the ODS surface, our study confirms that a significant amount of methanol solvent is extracted in the bonded ODS matrix (0.56-0.64 mL) compared to the column mobile phase volume (2.25 f 0.10 mL). Consequently, it appears feasible to study on-column reaction kinetics in the stationary as well as mobile phase for gaining further insight on the solvated stationary phase structure and composition. Calculations of Predicted Rate Constant Values in the Stationary Phase. In the literature, there appear to be four classifications of retention for interpreting the separation role of chemically bonded liquid chromatographic systems: partition, adsorption, pseudosorption, and generalized sorption (48-59). With the dynamic retention mechanism of RPLC columns inadequately explained by either simple partition or adsorption, attention has been focused in recent years on the last two categories. With the methanol mobile phase employed here, these would correspond to the following extremes: (1)Model I: Solute molecules interact with an associated methanol “pseudolayer” without the direct participation of the hydrocarbon ligands (59). ( 2 ) Model 11: Solute molecules interact with both stagnant methanol sheaths and bonded hydrocarbon ligands through a dispersion type of mechanism (a modification of the model of Burke et al. (49, 50)). The experimental evidence which is used to support a simple partition mechanism also can be explained by model I1 in which the net solute retention is directly proportional
to the total amount of bonded hydrocarbon attached to a specific silica with constant surface area for a specific mobile phase. This is because of the increase of the associated methanol volume with the increase of bonded hydrocarbon moieties. The simple adsorption mechanism can also be incorporated into model I by viewing solute molecules as competing with solvent molecules covering the external surface of the derivatized silica packings. Here, the modified packing is considered as a passive receptor to provide a surface on which the pseudolayer is coated (35-37). These two models are further examined here in terms of calculated reaction rates in the stationary phase using the conversion data from the chromatographic reactor. The predicted values of base-catalyzed reaction rate constants in the stationary phase, k:, from these two models can be estimated by using the rate constants in bulk methanol, chromatographic retention data, and pseudo-first-order kinetics. For model I
k’s,I = k(2)Meo~[catalyst], =
k(2)MeoH [catalyst]
[catalyst], [catalyst],,,
where k(2)is the second-order rate constant in methaol (M-l s-l); [catalyst] is the 4-picoline or pyridine concentration in designated phase, mobile (m) or stationary (s), KCAT is the base catalyst distribution coefficient between two phases, and V,,~ATis the retention volume of catalyst in the column. For model 11, since the experimental rate constants from the batch studies in the bulk methanol/octane solution are approximately proportional to the volumetric methanol concentration, eq 16 can be modified with an added “concentration factor” (c.f.) = (bulk rate constant in methanol) X (base catalyst concn in stationary phase) X (methanol concn (v/v) in stationary phase)
The value of the “effective”stationary phase volume, V,, varies with different models. For model I, the stationary phase would be regarded as consisting solely of the associated methanol layer, and thus transient solute molecules can only inhibit or “see” this pseudolayer volume; therefore, the stationary phase volume, V,, for two Altex Ultrasphere-ODS columns in series at 25 “C is 0.56 X 2 = 1.12 mL. For model 11, the stationary phase consists of both octadecylsilanes with the associated methanol layer. For the Ultrasphere-ODS columns, there is 12 wt % of carbon in 3.2-g silica packings per column (45); therefore, the amount of the bonded ODS content (20 carbon atoms) is (M.W.oDs = 311) = 0.5 g (18a) 3.2 g X 12% X 12 x 20 Since the bonded octadecyldimethylsilane density is not available in the literature, a density value of 0.931 g/mL at 25 “C for bulk ODS (35, 36) was used to estimate a volume of 0.5 mL of ODS present in each column although the bonded ODS density could be slightly lower. This is close to the volume of 0.48 mL which can be calculated from Colin and Guiochon’s molecular volume data (500 A3) for fully crowded grafted ODS ligands (35, 36, 60) (0.5/311)(6.02 x 1023)(500A3)= 0.48 mL (18b)
ANALYTICAL CHEMISTRY, VOL. 57, NO. 12, OCTOBER 1985
2201
Table I. Calculated Rate Constants for Reaction of TCTPClz in the Stationary Phase with Pulsed Liquid Chromatographic Reactor at 25 "C
catalyst 4-picoline
104k,104k,concn, M (batch), s-l (exptl)? s-l 0.00615
4-picoline 0.0082 pyridine
0.0050
pyridine
0.0075
104k,(calcd), (indicated model)
4.03 f 0.06 1.12 f 0.12 3.24 f 0.52 (I) 0.90 f 0.27 (11) 5.37 f 0.08 1.74 f 0.20 4.32 f 0.69 (I) 1.20 f 0.36 (11) 1.45 f 0.06 0.37 f 0.07 0.84 f 0.13 (I) 0.24 f 0.07 (11) 2.15 f 0.09 0.56 f 0.10 1.54 f 0.28 (I) 0.43 f 0.15 (11)
5
1
a
Calculated from eq 14.
D
catalyst 4-picoline
0.00615
4-picoline
0.0082
pyridine
0.0050
pyridine
0.0075
a
.
*
1
' 2000
-
2000
1000
*
I
1
*
I
4000
RETENTIONTIMEw c )
Table 11. Calculated Rate Constants for Reaction of TCTPClz in the Stationary Phase with Pulsed Liquid Chromatographic Reactor at 35 "C 104k,104k,concn, M (batch), s-l (exptl)," s-l
1000
0
104k,(calcd),s-l (indicated model)
7.26 f 0.06 2.41 f 0.27 3.97 f 0.45 (I) 1.25 f 0.25 (11) 9.68 f 0.08 3.62 f 0.40 6.06 f 0.68 (I) 1.80 f 0.36 (11) 2.55 f 0.10 0.77 f 0.12 1.20 f 0.19 (I) 0.37 k 0.11 (11) 3.80 f 0.15 1.56 f 0.28 2.38 f 0.43 (I) 0.75 f 0.24 (11)
Flgure 1. Series of liquid chromatograms for TCTPCI, esterification reaction catalyzed by 0.0075 M pyridine in methanol at 35 O C . Intermediate salt formation is illustrated. R is the reactant (TCTPCI,), I the inert standard (1-phenylheptane), M the intermediate product (N-(4-(chlorocarbonyI)tetrachlorobenzoyi)pyrkiiniumchloride), H the half ester impurity (methyl,Ci-TCTP),and C the catalyst vacancy peak (pyridine). Conditions were as follows: (a)flow rate 0.95 mL/min, AP = 2100 psi; (b) flow rate 0.32 mL/min, AP = 900 psi; (c) flow rate 0.21 mL/min, AP = 700 psi; (d) flow rate 0.11 mL/min, AP = 500 psi. I
Calculated from eq 14.
Table 111. Experimental and Calculated Rate Constants for Reaction of the Half Ester, Me, Cl-TCTP, in the Stationary Phase at 25 and 35 OC
catalyst
104k104k,concn, M (batch), s-l (exptl),"8-l
4-picoline 0.00615 (25 "C) 4-picoline 0.00615 (35 "C) pyridine 0.0075 (35 "C)
- Y ,
1600
,
,
, 3200
104k,(calcd),s-l (indicated model)
1.32 f 0.05 0.17 f 0.05 1.06 f 0.19 (I) 0.29 f 0.10 (11) 2.58 f 0.10 1.04 f 0.15 2.07 f 0.37 (I) 0.61 f 0.20 (11) 1.22 f 0.05 0.31 f 0.05 0.76 f 0.14 (I) 0.23 f 0.07 (11)
Calculated from eq 14. The calculated stationary phase rate constants are relatively insensitive to this density value; a 0.2 g/mL variation in density would not significantly affect the calculated k :,I values and would still yield the k values within the standard deviation of the reported data in Tables I, 11, and 111. The total stationary phase volume for two columns would then be 2(0.56 + 0.5) = 2.12 cm3 with solute molecules held by dispersion forces in this generalized phase. Estimation of the Apparent Rate Constants from the Pulse-Elution Liquid Chromatographic Reactor. Two liquid chromatographic column arrays were employed as chemical reactors to study the two-phase reaction kinetics. The pyridine or 4-picoline catalyzed esterization of tetrachloroterephthaloyl chloride (TCTPC12)in an octadecylsilane bonded liquid chromatographic reactor with methanol mobile phase was found to give satisfactory chromatograms for use for determining kinetics. The pulse-elution technique was employed to study reaction kinetics for the first step of the base-catalyzed esterification of TCTPClz in methanol; the structure of the intermediate product has been identified as quaternary N-(4-(chlorocarbonyl)-2,3,5,6-tetrachloro-
Flgure 2. Series of liquid chromatograms for the TCTPCI, (R) reaction catalyzed by 0.00615 M 4-picoline (C) in methanol at 35 O C . The system consists of two 4.6mm id. X 25 cm Aitex Ultrasphere-ODS columns in series. I indicates the inert standard (1-phenyloctane),M' is the intermediate product (N-(4-(chlorocarbonyl)tetrachlorobenzoylF4-picolinium chloride), and H is the half ester (methyl,CI-TCTP). Moblie phase flow rate was (a)0.32 mL/min, (b) 0.21 mL/min, and (c) 0.11 mL/min. benzoy1)pyridinium (M) or -picolinium chloride (M') salts (eq 19) with 13C FT-NMR and other techniques (32) (see Figures 1 and 2). c1
c1
c1
c1
ci
Ci
(M)
A typical series of reaction chromatograms at various flow rates at 35 "C for 0.0075 M pyridine and 0.006 15 M 4-picoline catalyzed reactions in the liquid chromatographic reactor are illustrated in Figures 1 and 2. It can be noted that the final
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ANALYTICAL CHEMISTRY, VOL.
57, NO. 12,OCTOBER 1985
0
2000
lo00
RETENTION TIME [sec)
V 6000 I
" 7200
'
8400 '
9600 '
I
Figure 3. Series of liquid reactor chromatograms for the K,CI-TCTP (H) reaction catalyzed by Cpicoline (C) in methanol at 25 'C. Iis the inert standard (1-phenylheptane) and 0' the intermediate product
(N-(4-(methoxycarbonyl)-2,3,5,6-tetrachlorobenzoyl)-4-picolinium
Flgure 4. First-order plot of area ratio A ,/A I vs. reactant retention time on a semilogarithm scale for TCTPCI, reaction at 25 'C (0)and 35 'C (W). Mobile phase was 0.0075 M pyridine, 0.123 M THF in methanol; stationary phase was bonded Ultrasphere-ODS (5 pm) packing. r
chloride). Mobile phase flow rate was (a) 0.21 mL/min, (b) 0.11 mumin, and (c) 0.056 mL/min. Stationary phase was Ultrasphere-ODS (Altex); mobile phase was 0.006 15 M 4-picoline in methanol.
product (dimethyl tetrachloroterephthalate) of the esterification reaction (21,32) did not form within the time of interest (
