In the Laboratory edited by
Advanced Chemistry Classroom and Laboratory
Joseph J. BelBruno Dartmouth College Hanover, NH 03755
An Easy Experiment To Compare Factors Affecting the Reaction Rate of Structurally Related Compounds Sandra Signorella, Silvia García, and Luis F. Sala* Departamento de Química-Física, Facultad de Ciencias Bioquímicas y Farmacéuticas (UNR), Suipacha 531-2000 Rosario, Argentina
When learning kinetics, students have to deal with kinetic laws, derive mechanisms, explain feasibility of the proposed mechanism, and compare data, when possible, with results obtained for similar reactions undertaken under similar experimental conditions, in order to explain the factors affecting the reaction kinetics. To accomplish the last step, it is interesting to have a set of related reactions (i.e., with slightly different reactants, for which the differences might be the configuration at a particular carbon atom, different functional groups, cyclic and open chain forms, etc.). Comparative analyses of experimentally obtained kinetic data prompt the student to inquire about the structural features that govern a reaction. Thus, the student learns new skills to develop a self-criterion for evaluating alternatives to select the most appropriate one. Here, we describe an exercise for training students in chemical kinetics. It involves the oxidation of polyols with potassium dichromate. The reactivities of the different polyols are compared and differences are interpreted in terms of the stereoelectronic factors influencing the reaction rate. In each case, the relative value of the experimental rate constant is used to infer the role of the substituents in the reaction pathway. Selecting a Reaction To Study Comparing factors affecting the reaction rate requires that the selected reaction be simple and short. Some advantages of the oxidation of diols and carbohydrates by CrVI are: 1. The reactants are commercially available. 2. 3. 4. 5.
The reaction is easy to perform. The overall reaction is the same in every case. The reaction takes place during a short time. The reaction is a model to mimic the environmental pollution caused by chromium.
Providing General Information on the Selected Reaction (the Oxidation of Monosaccharides by CrVI) Carbohydrates are very common in the natural world, and their polyfunctionality allows them to coordinate and chelate metal ions. The study of the oxidation of monosaccharides by CrVI enables us to compare the reactivities of monosaccharides towards CrVI. This is important because of the potential biological and ecological hazards posed by this element (1). For this reason, it is interesting to look *Corresponding author. Email:
[email protected].
HOH2C
O
OH
HOH2C +
HO
O
O
CrVI
OH
CrIV
+ HO
OH
OH OH
Figure 1. Two-electron oxidation of an aldohexose by CrVI .
at the ability of monosaccharides to reduce CrVI to CrIII, which is relevant to the transport of metal ions through soil, causing environmental pollution. A simple approach is to compare the reducing capabilities of the simple sugars by reacting them with dichromate under the same reaction conditions: temperature, [H+], ionic strength, and initial concentrations of reactants. The overall reaction implies the oxidation of the monosaccharide hemiacetalic function to the carboxylate group and the reduction of CrVI to CrIII. In all the studied cases, if the sugar is in large excess over [CrVI], the reaction products are the lactone and CrIII. Because two electrons are required to oxidize the aldose to the lactone, CrIII is not formed directly from CrVI, but requires a further one-electron reduction of CrIV by the sugar. Intermediate CrIV species are more reactive than CrVI and they are involved in faster steps. Therefore, we limit our concern to the slow, twoelectron redox process (Fig. 1). Some Questions Pointing Out the Goals of the Practical Exercise An interesting question is, why does the reaction rate differ from one sugar to another? At first glance, we can state that different stereoisomers have different physical and chemical properties, so there is no reason to think they should react at the same rate. That is correct. But we can also try to explain -
1. Why one monosaccharide reacts faster than the other. 2. Why the reactivity order is deoxyaldose > aldose >> aminoaldose. 3. Whether the configuration of a hydroxyl group distant from the oxidation site (C-1) can influence the reactivity of the monosaccharide.
Performing the Experiments D-Glucose (glc), D-allose (allo), D -galactose (gal), 2deoxy-D-glucose (2dglc), 2-deoxy-2-amino-D-glucose (2Nglc), sorbitol, DL-2,3-butanediol, and potassium dichromate were used without further purification. Ethanol was heated at reflux over iodine–magnesium and distilled before being used
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in the kinetic determination (2). DL-1,2-Propanediol was dried on sodium sulfate, decanted, and distilled under reduced pressure (3). Ethylene glycol was dried with CaO and distilled under vacuum (3). Perchloric acid solutions were prepared from 70% perchloric acid. The purity of the liquid substrates was checked by measuring their density. Aqueous solutions containing 200:1 substrate:CrVI mole ratio were prepared by adding potassium dichromate solutions to water containing the required amount of substrate and adjusting the [H+] by adding perchloric acid to a final concentration of 1 M. CAUTION: All CrVI compounds are toxic and potential carcinogens. Chromic acids are corrosive and should be handled only by individuals wearing protective eyewear and protective clothing. Concentrated perchloric acid is oxidizing and corrosive, so keep away from combustible material, do not breathe vapors, and avoid contact with skin, eyes, and clothing. Kinetic measurements were made at 350 nm by monitoring the absorbance changes on a Guilford Response II spectrophotometer with fully thermostated cell compartments. Reactant solutions were previously thermostated and transferred into a cell of 1-cm path length immediately after mixing. Disappearance of CrVI was followed until at least 80% was converted (Fig. 2). Experiments were performed at 40 °C. The initial concentration of CrVI was kept constant at 6.0 × 10{4 M. Except for 2Nglc, the observed pseudo-first-order rate constants (kobs) were determined from the linear part of plots of ln(A350) vs time. The observed deviations from firstorder decay at very short time periods are due to the superimposition of the absorbance of intermediate CrV species (4 ). The kobs deduced from multiple determinations were within ± 5% of each other, and their values are listed in Table 1. For the oxidation of 2Nglc, kobs was obtained by using the initial rate approach: kobs = {v0 /(A0 – A∞), where A0 and A∞ are the A350 at t = 0 and t = ∞ and v0 ({dA350 /dt when t → 0) was calculated following the method proposed by Chandler et al. (5). Discussing the Experimental Results
Factors Affecting the Oxidation Rate of Diols by Chromate Before dealing with carbohydrates, we will discuss the relative abilities of alcohols and diols to reduce chromate, by considering the factors influencing the reaction rate. First, we will consider the mechanism generally accepted for the oxidation of alcohols and then we will analyze the relative oxidation rates of several diols included in Table 1. The oxidation of alcohols and glycols has been extensively studied (6, 7 ). The generally accepted mechanism consists of two steps: the formation of a chromate ester, followed by the slow redox step to yield the oxidation product and CrIV: R–OH + HCrO4{ I → R= O + CrIV The slow redox step corresponds to an intramolecular α-hydride transfer step into the five-membered cyclic transition state shown in Figure 3a. The first step in the reaction of aliphatic 1,2-diols as well as cyclic cis-1,2-diols with CrVI involves formation of a five-membered chromate chelate, followed by the hydride transfer in a bicyclic intermediate
406
state (Fig. 3b). In contrast, the cyclic intermediate chromate esters are not formed with cyclic and aliphatic 1,3-diols and the second hydroxyl function only retards the reaction rate, meaning that the cyclic chromate ester cannot form readily into a six-membered structure. The effect of an α-substituent on the rate of oxidation of diols is to enhance the oxidation rate as the number of alkyl substituents increases. Eliminating a number of unstable conformations of the chromate ester, the hindrance of the substituent increases the probability of attaining the fivemembered cyclic transition state. This steric acceleration of the decomposition of the chromate ester as a controlling factor in the overall rate of oxidation may be observed by comparing the pseudo-first-order rate constants (Fig. 4a) for the 1,2-diols in Table 1. It is interesting to note that sorbitol
Figure 2. Spectrophotometric time scanning for the reaction of Cr VI (6.0 × 10 {4 M) with (a) sorbitol, (b) 2,3-butanediol, (c) 1,2propanediol, (d) gal, (e) allo, (f) 2dglc, (g) glc, (h) ethylene glycol, (i) 2Nglc, at 350 nm. Conditions: [HClO4] = 1 M; T = 40 °C, [substrate]/[CrVI ] = 200:1.
Table 1. Obser ved Pseudo-First-Order Rate Constants for Oxidation of Polyols by CrVI
k obs /s {1
Substrate Sorbitol
1.79(3) × 10 {2
2,3-Butanediol
1.79(4) × 10 {2
1,2-Propanediol
1.02(1) × 10 {2
Ethylene glycol
0.86(2) × 10 {3
D-Galactose
3.53(5) × 10 {3
D-Allose
3.07(1) × 10 {3
2-Deoxy-D-glucose
2.74(4) × 10 {3
D-Glucose
1.30(3) × 10 {3
2-Deoxy-2-amino-D-glucose
1.95(2) × 10 { 4
N OTE: [HClO4] = 1.0 M; [Cr VI]0 = 6.0 × 10{4 M; [S]0 /[CrVI]0 = 200; T = 40 °C.
Journal of Chemical Education • Vol. 76 No. 3 March 1999 • JChemEd.chem.wisc.edu
In the Laboratory
O
O H (a)
C
Cr O O
H
Cr H
(b)
O
–
O
RO
H R
Figure 3. Transition state for the intramolecular hydride transfer in the oxidation of (a) alcohols and (b) 1,2-diols by chromate.
(a) OH
OH OH CH2OH
HOH2C
OH
OH
OH OH sorbitol
CH2OH CH2OH
HO
2,3-butanediol
=
1,2-propanediol
>
ethylene glycol
>
(b) HOH2C
O
HO
OH
HOH2C
OH
HO
O
gal
HOH2C
>
O
OH
>
O
HO
HO OH >
OH
glc
OH
HOH2C
OH
HO
O
OH NH2
OH
OH
2dglc
OH
OH
allo
HOH2C
O
HO
OH OH
OH
(c)
OH HOH2C
glc
>
2Nglc
Figure 4. Relative Cr VI oxidation rates of (a) alcohols; (b) aldohexoses; (c) aldohexoses differing in the substituent at C-2.
OH R HO
(a)
R
O OH
O
HO
OH OH
OH
gal
OH
allo R
O
HO HO
OH
OH
glc
– O
O
H
(b)
Cr
H O
O O
OH
Figure 5. (a) Pyranosic chair forms of the aldohexoses under study, with R = CH 2OH. (b) Intermediate chromate chelate.
is oxidized as fast as 2,3-butanediol. This means that in both cases the first step should be the formation of a five-membered chromate chelate precursor of the redox steps (at least two chromate chelates are formed with sorbitol via the syn-2,3and syn-3,4-diol moieties), and the effect of the methyl groups in 2,3-butanediol is comparable to the effect of the hydroxyalkyl moieties. This result is also evidence that the number of substituents is more important than their nature.
Factors Affecting the Oxidation Rate of Monosaccharides by Chromate It is commonly accepted that aldoses react with CrVI in their cyclic hemiacetal form. The aldoses offer more binding sites than glycols and can act as bidentate or tridentate ligands to form several linkage isomeric monochelates. When the sugar is in large excess over CrVI, the only reaction product is the corresponding lactone (oxidation of the hemiacetal C-1–OH group to carboxylate), and so only those isomers with the C-1–OH bound to CrVI should be considered as redox reactive species, whereas the other isomers are in rapid equilibrium with them. The observed pseudo-first-order rate constants obtained for different sugars are listed in Table 1. First, we will consider the relative reaction rates of aldohexoses (Fig. 4b). As in the case of diols, the reaction rate depends on the rate of formation of a sugar–CrVI chelate and the rate of the electron-transfer (redox) step. In a general way, kobs may be written as kobs = k Kc [aldose], a kinetic law corresponding to the formation of an intermediate chromic acid ester formed in a pre-equilibrium, where K c is the kinetic constant for the formation of the chelate: aldose + CrVI
Kc
k
aldose–CrVI → P I
We will assume that the redox steps in the intermediate complex take place through an intramolecular hydride transfer. If we consider that the redox rates for the aldohexoses are as fast as for alcohols (under conditions used in this work, the kobs for ethanol is 2.56(3) × 10 {3 s{1), for which an intramolecular hydride transfer takes place, it seems reasonable to suppose that this is also true for sugars. In the present case, the relative rate of reduction of Cr VI by different aldohexoses should depend on the stereochemistry of the sugar. Several observations are valid for all the aldohexoses. The C-1–OH function reacts faster than the primary or any of the secondary OH groups. The lactone as the only reaction product easily proves this. As a consequence, the first step should imply a five-membered chelate chromate (as for diols, the five-membered chromate esters are the most favorably formed) with the C-1–OH group as one of the coordination sites. The oxidation rates of the sugars are slower than those observed for diols and polyols (e.g., sorbitol) as a result of the rate-retarding effect resulting from a higher “stabilization” of the intermediate chromate chelate. If we compare the stereochemistry of the aldohexoses under study, the relative oxidation rates may be interpreted as follows. For the sake of simplicity, we will consider only the pyranoses in their chair conformations, as shown in Figure 5a. The configuration of C-1 is not specified because a mixture of the α- and β-anomers exists in the equilibrium, and both of them are reactive toward CrVI. Then, we can describe the CrVI chelation as in Figure 5b. The monosaccha-
JChemEd.chem.wisc.edu • Vol. 76 No. 3 March 1999 • Journal of Chemical Education
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In the Laboratory
ride that forms the less “stable” aldose-CrVI chelate with the bicyclic structure required for the intramolecular hydride transfer (the intermediate of Fig. 5b) will be that with the higher redox rate. A comparison of the reactivity of these aldoses reveals that the axial C-4–OH in the gal stereoisomer has the highest rate-accelerating effect, followed by the axial C-3–OH in allo; glc, with all the ring substituents in pseudoequatorial position, forms the most “stable” chelate and is oxidized slower than the two other aldohexoses. Thus, the rule we can deduce is: the axial substituents on the sugar ring accelerate the oxidation rate, the effect being stronger when the axial substituent is on C-4 than on C-3. Now, let us compare the relative reactivity of 2dglc, glc, and 2Nglc (Fig. 4c). The C-2–OH is involved in the chelation of CrVI in the oxidation of aldoses, as may easily be deduced from the enhancement of the oxidation rate of 2dglc compared to glc (see values of kobs in Table 1). In the case of 2dglc, the chromate intermediate species is formed with 2dglc binding CrVI essentially at C-1–OH. Thus, the weaker binding of 2dglc to CrVI accelerates the redox step. In contrast, the presence of the amino group at C-2 considerably reduces the reactivity of the sugar. We can correlate this behavior with the formation of a more “stable” chelate with the C-2–N as a donor site. We can further assume that with the nitrogen donor site, a conformation favoring the hydride transfer cannot be achieved; therefore a hydrogen atom transfer to the solvent (the H atom transfer is slower than the hydride transfer) should occur in the rate determining step.
408
Conclusions This exercise combines an experimental part (measurement of the rate constants) and a discussion of the experimental results in terms of factors responsible for the observed differences. The reactivity trends are ascribed to: 1. the role of the substituent in the reactivity of diols 2. the role of the C-3 and C-4 configuration in the reactivity of aldohexoses 3. the role of the C-2 substituent in the reactivity of aldohexoses
and arguments are given to explain them. Acknowledgments We thank the National Research Council of Argentina (CONICET), the Third World Academy of Sciences (TWAS), the National University of Rosario, and the International Foundation for Sciences (IFS) for financial support. We thank R. Cargnello for technical work. Literature Cited 1. Katz, S. A.; Salem H. The Biological and Environmental Chemistry of Chromium; VCH: New York, 1994. 2. Vogel, A. A Text Book for Practical Organic Chemistry, 3rd ed.; Longman: London, 1956. 3. Purification of Laboratory Chemicals, 2nd ed.; Perrin, D. D.; Armarego, W. L F.; Perrin, D. R., Eds.; Pergamon: New York, 1980. 4. Signorella, S.; Rizzotto, M.; Mulero, M.; García, S.; Frascaroli, M.; Sala, L. F. J. Chem. Educ. 1992, 69, 578–580. 5. Chandler, W. D.; Lee, E. J.; Lee, D. G. J. Chem. Educ. 1987, 64, 878–881. 6. Beattie, J. K.; Haight, G. P. In Inorganic Reaction Mechanisms, Part II; Edwards, J. O., Ed.; Wiley: New York, 1972. 7. Mitewa, M.; Bontchev, P. Coord. Chem. Rev. 1985, 61, 241–272.
Journal of Chemical Education • Vol. 76 No. 3 March 1999 • JChemEd.chem.wisc.edu
