The Finkelstein Reaction: Quantitative Reaction Kinetics of an SN2

In the Laboratory

The Finkelstein Reaction: Quantitative Reaction Kinetics of an SN2 Reaction Using Nonaqueous Conductivity

W

R. David Pace* and Yagya Regmi Department of Science and Mathematics, Lyon College, Batesville, AR 72503; *[email protected]

The multidisciplinary area of chemical kinetics constitutes perhaps the largest single source of information for understanding reaction mechanisms in organic chemistry (1). Within the last decade, many excellent reports have appeared in this Journal dealing with the study of kinetics at the undergraduate level (2). Additionally, a multitude of computerbased simulations have been shown to demonstrate the principles of kinetics (3). Although specific course pedagogy is instructor-dependent, it is generally true that little time in the introductory undergraduate organic chemistry course is devoted to understanding kinetics as it relates to the elucidation of reaction mechanisms. However, a study of reaction kinetics in the organic chemistry sequence provides a forum for students to explore fundamental structure–reactivity relationships, solvent–reactant interactions, and transition-state energies. These concepts are integral to an understanding of the fundamental chemistry of carbon compounds if we expect students to transcend the tendency to memorize volumes of reaction characteristics. It is for this reason that we have chosen to include a detailed examination of reaction kinetics in the second-year organic chemistry sequence. Many reasons may be offered to explain the omission of kinetics from the undergraduate organic curriculum, but there are three primary reasons. First, the sheer volume of organic chemistry that must be covered in the second-year sequence precludes the addition of such a large topic as chemical kinetics. However, the use of a well-designed kinetics laboratory exercise offers a partial solution. Second, most second-year organic students are not majoring in chemistry and may have weak math skills. Third, there is a paucity of facile quantitative chemical or instrumental methods available to large organic chemistry lab sections. Recently, many excellent kinetics experiments have appeared in this Journal utilizing sophisticated instrumental methods including nuclear magnetic resonance (4), GC–MS (5), spectrophotometry (6), infrared spectroscopy (7), and a LabWorks computer pressure sensor interface (8). In one way or another, each of these methods requires the availability of expensive instru ments or logistically complex methods. However, some kinetics experiments have appeared that employ cost-effective, homemade analytical devices (9). We have developed a quantitative kinetics experiment for the second-year organic laboratory based on the well-known SN2 reaction of iodide ion with alkyl halides, the Finkelstein reaction,

H2RC – X + NaI H

acetone

‡

H

I

X

H2RC – I + NaX

R

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(1)

utilizing an economical and easy-to-use nonaqueous conductimetric analytical method. Sodium iodide is soluble in acetone, and as the transhalogenation proceeds (the exchange of Cl or Br for I), acetone insoluble sodium halide (chloride or bromide) precipitates, thus driving the reaction to completion (Le Châtelier’s principle). Since the concentration of the acetonesoluble salt changes as the reaction proceeds, the ionic strength of the reaction mixture decreases as a function of time. An economical and commercially available conductivity meter is used to follow the change in concentration of sodium iodide as a function of time. Two dated references (10) indicated conductance may be unsuitable for following the kinetics of this reaction. Modern conductivity devices appear to have circumvented such problems. Although polarization is still a concern, modern conductivity devices minimize polarization by limiting solution conductivities to less than 30 mS兾cm, using high frequency AC to power the probe and keeping the current density low (11). Given the repeatability of this experiment, it is evident that nonaqueous conductivity is a viable analytical tool for quantifying the kinetics of the Finkelstein reaction. Several aqueous (12) and nonaqueous (13) conductimetric analytical methods have appeared in this Journal. The experiment described herein provides an excellent introduction to the deductive process of using kinetic studies to draw relevant mechanistic conclusions. From a historical perspective, the Finkelstein reaction is one of the most well-known and studied reactions in organic chemistry (14). There is a multiplicity of other methods available for the synthesis of alkyl iodides, including the reaction of I2 with silver or lead carboxylate salts (the Hunsdiecker reaction) (15), the reaction of HI with alcohols (16), the cleavage of ethers with HI (17), and the cleavage of carboxylic esters with lithium iodide in pyridine (18). Complex kinetics and toxic reagents preclude the consideration of these halogenation reactions for an undergraduate kinetics experiment. On the other hand, the Finkelstein reaction is a classic and straightforward overall second-order process that is first order in alkyl halide and first order in metal halide. Although not commonly considered reversible, the Finkelstein reaction is an equilibrium process. The degree of reversibility (e.g., position of equilibrium) is dependent upon several factors, including nucleophilicity of the attacking halide, the nature of the leaving halide, and the extent of solvation of the anions (nucleophile and leaving group). Since iodide is a better leaving group than bromide or chloride, this transhalogenation reaction is often utilized to replace a bromine or chlorine with iodine to facilitate a subsequent nucleophilic substitution (19). In the undergraduate introductory organic chemistry course, this reaction is typically introduced in order to explore relative rates of alkyl halide reactivity (20), or

Vol. 83 No. 9 September 2006

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In the Laboratory Table 1. Calibration Cur ve Results for Conductivity, κ, κ, versus √[NaI] Solvent

T/⬚C

Equation

r

2 a

σmc/10᎑4

Sb

σbc/10᎑3

Acetone

20

√[NaI] = 0.0365κ + 0.0601

0.996

0.0505

6.58

05.58

Acetone

30

√[NaI] = 0.0363κ + 0.0549

0.994

0.188

8.14

06.98

Acetone

40

√[NaI] = 0.0360κ + 0.0583

0.994

0.125

7.78

06.70

Acetonitrile

40

√[NaI] = 0.0184κ + 0.0761

0.981

0.0467

7.42

11.9

a 2

r is a measure that may be regarded as the percent of the total variation of y that is explained by the linear (in this case) relationship

with x. bThe standard error, S, is an expression of the degree of error contained in the prediction of y for a given x (24a). standard deviation of the slope is σm, and the standard deviation of the y intercept is σb (24b, 24c).

c

The

Table 2. Experimental Results Exp

Substrate/Solvent

No. of Runs, n

T/⬚C

a

Rate Constant, k (where y = kx + b) k/(10−4 −1 −1 L mol s )

1a

1-Bromobutane/Acetone

20

2

1b


30

2a

23.2

7.99 50.9

σm

b

σb

0.28

2.78

0.04

0.6

2.47

0.08

1c


40

3

1.7

2.78

0.13

2


40

3

0.879

0.115

2.71

0.01

3

1-Chlorobutane/Acetone

40

2c

0.155

0.045

0.987

0.010

40

3

8.24

0.23

2.86

0.03

4

b

1-Bromobutane/Acetonitrile

d

a

Two student groups used the same conductivity meter that had a probe fouled with sodium bromide. Therefore, these values b c The dielectric constant for acetone is 20.7. Insufficient number of students to make this were excluded from the analysis. d run. The dielectric constant for acetonitrile is 37.5.

it is used as a qualitative analysis for primary alkyl chlorides or bromides (21). A quantitative kinetic study of this reaction within the undergraduate organic chemistry laboratory is limited by the few practical analytical methods available for measuring the changing concentrations of alkyl halides or inorganic salts. However, two recent reports in this Journal describe a lecture demonstration of the relative kinetics of this reaction using a cleverly constructed qualitative conductivity apparatus (22). Given this use of conductivity for the qualitative analysis of this reaction as well as the commercial availability of analytical conductivity meters today, it seemed logical to expand the investigation to a quantitative analysis of the kinetics of the SN2 reaction of iodide ion with alkyl halides. Although conductance of electrolytic solutions is a topic typically introduced in the first-year general chemistry sequence, little mention is made of the mathematical and theoretical basis of conductivity. A discussion of the general concepts of conductivity may be found in the Supplemental Material.W Equation 2 is a fundamentally important conductivity expression in which conductivity, κ, is proportional to the square root of the strong electrolyte (e.g., NaI) concentration (23). κ ∝

[ NaI ]

(2)

This experiment explores solvent polarity, reaction temperature, steric bulk of the reacting alkyl halide, and leaving group ability on the rate of the Finkelstein reaction. The experiment must be conducted over two laboratory periods. Calibration curves are built during the first laboratory pe-

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riod, while the actual kinetics experiments are conducted during the second laboratory period. If the instructor opts to provide students with necessary calibration curves, then the entire exercise may be telescoped to one laboratory period. Depending upon the size of the class and equipment availability, students may work individually or in groups. Upon completion of the second laboratory period, students pool their data, and then they complete the data analysis and prepare a laboratory report on an individual basis. Replicate kinetic runs may be performed and examined on a statistical basis. Experiment The first laboratory period involves the preparation of a series of sodium iodide solutions in acetone and acetonitrile. These solutions may be prepared from concentrated stock solutions by successive volumetric dilutions (approximate concentration range: 2.7 × 10᎑3 M to 4.1 × 10᎑1 M). Calibration curves are prepared for acetone at 20, 30, and 40 degrees Celsius. Only one calibration curve for acetonitrile at 40 degrees Celsius is required. Each student or group prepares one calibration curve. Replicates may be averaged. Typical calibration results are summarized in Table 1. Complete calibration curve data as well as a detailed procedure are available in the Supplementary Material.W The second laboratory period involves the actual acquisition of kinetics data. Each student or group should be assigned no more than two kinetics experiments, depending upon class size, as summarized in Table 2. Again, replicate data sets increase the significance of the results. Each stu-


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In the Laboratory

ritant, and a possible carcinogen. 2-Iodobutane is flammable, an irritant, light sensitive, and harmful by ingestion, skin, contact, or inhalation. Results

Figure 1. Kinetic plots of 1-bromobutane in acetone at 20, 30, and 40 ⬚C. The linear regression data are shown in Table 2.

Calibration plots of √[NaI] versus conductivity at 20, 30, and 40 degrees Celsius in the prescribed solvents are linear. Kinetic plots of 1兾[NaI] versus time, ln[NaI] versus time, and [NaI] versus time clearly demonstrate that this reaction is second order in [NaI] because only the 1兾[NaI] plot is linear. Reaction times are limited to a maximum of 50 minutes in all cases because the Finkelstein reaction is considered to be irreversible over the first 30–50% of the reaction (26). This is due to the fact that the product inorganic salt (sodium bromide) is not completely insoluble in acetone. The sodium bromide concentration becomes appreciable past this point, and the kinetics become more involved because the reaction becomes reversible. During the development phase of this experiment, reaction times (tfinal) were adjusted according to, fraction NaI remaining = at t final

Figure 2. Arrhenius plots of 1-bromobutane–NaI in acetone.

dent or group records their data on the master data sheet. At the end of the laboratory period, photocopies of the master data sheet are distributed to all students. The complete experimental procedure and examples of the master data sheets are contained within the Supplementary Material.W Table 2 does not include experiments for 2-bromobutane and 1-chlorobutane in acetonitrile. While these experiments would contribute nicely to the series, the reaction rates in each case are significantly depressed owing to solvation of the nucleophile (25). It is not possible to carry out these reactions within the time frame of a typical organic laboratory meeting. With a sufficiently large class, the instructor may opt to include a study of the effect of reactant concentration on the rate of the Finkelstein reaction as summarized in Table 4 (vide infra). Hazards 1-Bromobutane and 1-bromobutane are flamable, harmful if inhaled or ingested, and skin and eye irritants. 1-Chlorobutane is flamable and a skin, eye, and respiratory tract irritant. Sodium iodide is an eye and skin irritant and a possible allergen and teratogen. Acetone is flamable, an eye and skin irritant, harmful if inhaled or ingested, and affects the central nervous system. Acetonitrile is an unusual fire hazard; may cause skin and eye irritations and allergic reactions; may be absorbed in harmful quantities; and is a possible teratogen and mutagen. 1-Iodobutane is flammable, a severe ir-

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[ NaI ]final [ NaI ]0

× 100% = 50% to 70% (3)

such that the final sodium iodide concentration at tfinal was approximately 50–70% (this corresponds to 30–50% conversion to products) of the initial sodium iodide concentration. Rate constants, k, may easily be determined from the slopes of the kinetics plots. Additionally, for 1-bromobutane in acetone the activation energy, Ea, is easily obtainable from the slope of the Arrhenius plot of ln k versus 1兾T. Data tables, graphs, and mathematical analyses appear in the Supplemental Material.W Typical experimental data are summarized in Table 2. Students draw conclusions concerning the selected reaction conditions by estimating the magnitudes of the effects using the average rate constants. For instance, a comparison of experiments 1a, 1b, and 1c allows students to observe the effect of temperature on the rate constant as shown in Figure 1. Then, the Arrhenius plot provides the Ea for the reaction of 1-bromobutane with sodium iodide in acetone as shown in Figure 2 (slope = ᎑Ea兾R; if R = 1.99 cal兾(mol K), then, Ea = 16.9 kcal兾mol = 4.05 kJ兾mol). Table 3 summarizes the other pertinent results that may be obtained from a comparison of rate constants. Additionally, comparisons of these rate constant data with published sources (26–28) may be accomplished using eq 4 in order to compensate for the negative salt effect. However, it must be stated that this only an approximation owing to the fact that this equation was originally derived based on lithium halide chemistry logg kcorr = log kexp + 0.37 log

c 0.024

(4)

where, kcor is the rate constant corrected for the difference in salt concentration, kexp is the student’s experimental rate con-


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In the Laboratory

Table 3. Summary of Relative Rate Constants Rate Const Ratio

Effect

Conclusions

k1 c /k3 = 328

Leaving group ability

As predicted from periodic table, Br− is a better leaving group than Cl− . Additionally, the rate constants parallel carbon-leaving group bond strengths (C–Cl, 83.5 kcal/mol and C–Br 70 kcal/mol)

k1 c /k2 = 57.9

Steric bulk of the substrate

Owing to difficulty in achieving the transition state, the 2 alkyl bromide reacts more slowly than the 1o alkyl bromide.

k1 c /k4 = 6.18

Solvent type and polarity

Polar aprotic solvents are best for SN 2 reactions. The reaction is slower in acetonitrile − because the more polar acetonitrile (ε = 37.5) solvates the nucleophile (I ) to a greater extent than acetone (ε = 20.7).

o

stant, c is the student’s initial NaI concentration. Equation 4 corrects back to the original Ingold work (28). Specifically, eq 4 corrects for the effect of salt concentration on the rate constant. In these initial kinetics studies, the initial concentration of the metal halide was approximately 0.024 M. Equation 4 is limited to the comparison of results for systems in which the initial metal halide concentration is in this range. Finally, eq 5 may be used to compare rate constants at different temperatures (29). ln

k2 E 1 1 = a − k1 R T1 T2

(5)

At this point, it should be noted that the special condition, where [NaI]0 = [RX]0, was used in all cases (except for 1-chlorobutane; experiment 3, Table 2) in order to employ the simplified integrated second-order rate expression shown in eq 6. 1 = [ NaI ]t

1 + kt [ NaI ]0

(6)

Achieving a 1:1 ratio of reactants was facilitated through the use of calibrated micropipets. However, students may find the general second-order expression, ln

[ RX ]t [ NaI ]0 [ RX ]0 [ NaI ]t

=

[ RX ]0 − [NaI]0

kt

(7)

where [NaI]0 ≠ [RX]0, to be a more convenient manipulation from an experimental standpoint. Nevertheless, this lab exercise is directed towards the determination of the rate constants for various permutations of the Finkelstein reaction. For any given reaction conducted at a specific temperature, the value of k may be determined from either eq 6 or 7 depending upon the initial reactant ratio. For comparative purposes using the method of initial slopes, the results of two single runs for the reaction of 1-bromobutane with NaI at 40 ⬚C ([RX]:[NaI]) of 4:1 and 2:1) were analyzed with respect to the 1:1 result from experiment 3 of Table 2 (Table 4). As expected, the rate constant for this reaction does not change with changing reactant ratio, but the rate does change. The doubling of the rate upon doubling the 1-bromobutane concentration clearly demonstrates that the reaction is first-order in 1-bromobutane.

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Conclusion Students have given favorable responses to this laboratory exercise. This laboratory experiment does require the student to exercise careful analytical techniques, mathematical skills, and spreadsheet manipulation capabilities. However, these are fundamental skills any competent second-year chemistry student should possess. Following the progress of the Finkelstein reaction using conductivity is an easily understood method that is useful for determining the rate of a reaction in which the ionic strength of the solution changes over time. From our standpoint, the only limitation to this experiment may be due to a finite number of available conductivity meters. W

Supplemental Material

A complete resource for instructors and students, including instructor information, a summary experimental data sheet, student data, experimental graphs, post-laboratory questions, background for students (SN2, kinetics, and conductivity), a detailed student procedure, and data analysis instructions is available in this issue of JCE Online. Acknowledgments The authors wish to thank Lyon College for the support of this work, Floyd Beckford (Lyon College), Kurt Grafton (Lyon College), and Warren Jackson (Eastman Chemical Company) for helpful conversations and advice,

Table 4. Effect of Reactant Ratio on the Rate and Rate Constant Eq

Rate/ (10᎑4 mol L᎑1 s᎑1)c

Rel Rate

4:1

b

45.7

7

20.0

3.8 ≈ 4

2:1

44.8b

7

11.2

2.1 ≈ 2

1:1

d

6

05.20

1

[RX]a:[NaI]

k/ (10᎑4 L mol᎑1 s᎑1)

50.9

a

RX is 1-bromobutane. bThese data were collected by one author (RDP). cRates calculated from 0 seconds to120 seconds. dThis value somewhat disagrees with the other values. This value, taken from Table 2, is part of the student-generated data set. The three student-determined values for were: 54.4 x 10᎑4, 46.3 x 10᎑4, and 51.9 x 10᎑4.


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and the reviewers of the manuscript whose comments strengthened this article. Additionally, the authors would like to thank students of the 2004–2005 organic chemistry class for providing the data used in the preparation of this manuscript. Literature Cited 1. Sykes, P. A Guidebook to Mechanism in Organic Chemistry, 6th ed.; Longman Scientific & Technical: Essex, United Kingdom, 1987; p 44. 2. (a) Weiss, H. M.; Touchette, K. J. Chem. Educ. 1990, 67, 707. (b) Prypsztejn, H. E.; Negri, R. M. J. Chem. Educ. 2001, 78, 645. (c) Stetca, D.; Arends, I. W. C. E.; Hanefield, U. J. Chem. Educ. 2002, 79, 1351. (d) Vetter, T. A.; Colombo, D. P. J. Chem. Educ. 2003, 80, 788. 3. (a) Bozzelli, J. W. J. Chem. Educ. 2000, 77, 165. (b) Muranaka, K. J. Chem. Educ. 2002, 79, 135. (c) Hanson, R. M. J. Chem. Educ. 2002, 79, 1379. (d) Vera, L. R.; Ortega, P. A.; Gozman, M. J. Chem. Educ. 2004, 81, 159. 4. (a) Minter, D. E.; Villarreal, M. C. J. Chem. Educ. 1985, 62, 911. (b) Potts, R. A.; Schaller, R. A. J. Chem. Educ. 1993, 70, 421. 5. Annis, D. A.; Collard, D. M.; Bottomley, L. A. J. Chem. Educ. 1995, 72, 460. 6. Jonnalagadda, S. B.; Gollapalli, N. R. J. Chem. Educ. 2000, 77, 506. 7. Bengali, A. A.; Mooney, K. E. J. Chem. Educ. 2003, 80, 1044. 8. Abrahamovitch, D. A.; Cunningham, L. K.; Litwer, M. R. J. Chem. Educ. 2003, 80, 790. 9. (a) Papageorgiou, G.; Ouzounis, K.; Xeros, J. J. Chem. Educ. 1994, 71, 647. (b) Poce–Fatou, J. A.; Gil, M. L. A.; Alcantara, R.; Botella, C.; Martin, J. J. Chem. Educ. 2004, 81, 537. 10. (a) Evans, A. G.; Hamann, D. S. J. Chem. Soc., Faraday Trans. 1951, 47, 30. (b) Skolink, H.; Day, A. R.; Miller, J. G. J. Am. Chem. Soc. 1943, 65, 1858. 11. Aquarius Technologies Technical Bulletin No. 8, August 2000. 12. (a) Rosenthal, L. C.; Nathan, L. C. J. Chem. Educ. 1981, 58, 656. (b) Cyr, T.; Prahomme, J.; Zador, M. J. Chem. Educ. 1973, 50, 572. (c) Mukherjee, L.; Reiter, R. J. Chem. Educ. 1972, 49, 698.

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13. (a) Brand, M. J.; Hiller, J. M.; Mohan, M. S. J. Chem. Educ. 1979, 56, 207. (b) Hill, J. W. J. Chem. Educ. 1976, 53, 778. 14. (a) Finkelstein, H. Ber. 1910, 43, 1528. (b) Epple, M.; Troger, L.; Hilbrandt, N. J. Chem. Soc., Faraday Trans. 1997, 93, 3055–3037. 15. Smith, M. B.; March, J. March’s Advanced Organic Chemistry, 5th ed.; Wiley Interscience: New York, 2001; pp 942–944. 16. Larock, R. C. Comprehensive Organic Transformations; VCH Publishers: New York, 1989; p 358. 17. Bhatt, M. V.; Kolkarni, S. U. Synthesis 1983, 249. 18. Larock, R. C. Comprehensive Organic Transformations; VCH Publishers: New York, 1989; pp 521, 522. 19. For example, see: Molander, G. A.; Brown, G. A.; Storch de Gracia, I. J. Org. Chem. 2002, 67, 3459. 20. Williamson, K. L. Macroscale and Microscale Organic Experiments, 3rd ed.; Houghton Mifflin Company: New York, 1999; pp 262–264. 21. Mayo, D. W.; Pike, R. M.; Trumper, P. K. Microscale Organic Laboratory with Multistep and Multiscale Syntheses, 3rd ed.; John Wiley & Sons: New York, 1994; p 710. 22. (a) Newton, T. A.; Hill, B. A. J. Chem. Educ. 2004, 81, 61. (b) Newton, T. A.; Hill, B. A. J. Chem. Educ. 2004, 81, 58. 23. (a) Coury, L. Current Separations 1999, 18, 91. (b) Onsager, L. Phys. Z. 1927, 28, 277, as cited in: Shoemaker, D. P.; Garland, C. W.; Steinfield, J. I.; Nibler, J. W. Experiments in Physical Chemistry, 4th ed.; McGraw–Hill: New York, 1981; p 232. 24. (a) Walpole, R. E.; Meyers, R. H. Probability and Statistics for Engineers and Scientists, 3rd ed.; MacMillan, Inc.: New York, 1985; pp 317–348. (b) Pattengill, M. D.; Sands, D. E. J. Chem. Educ. 1979, 56, 244. (c) Heilbronner, E. J. Chem. Educ. 1979, 56, 240. 25. Jones, R. A. Y. Physical and Mechanistic Organic Chemistry, 2nd ed.; Cambridge University Press: Cambridge, 1987; pp 163, 164. 26. Fowden, L.; Hughes, E. D.; Ingold, C. K. J. Chem. Soc. 1955, 3187. 27. de la Mare, P. B. D. J. Chem. Soc. 1955, 3169. 28. Le Roux, L. J.; Swart, E. R. J. Chem. Soc. 1955, 1475, as cited in ref. 13b. 29. Whitten, K. W.; Davis, R. E.; Peck, L. M. General Chemistry, 6th ed.; Saunders College Publishing: New York, 2000; p 685.


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The Finkelstein Reaction: Quantitative Reaction Kinetics of an SN2

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