In the Classroom edited by
Applications and Analogies
Ron DeLorenzo Middle Georgia College Cochran, GA 31014
An Acid–Base Chemistry Example: Conversion of Nicotine John H. Summerfield Department of Chemistry, Missouri Southern State College, Joplin, MO 64801;
[email protected] Much of the traditional general chemistry class focuses on the nuts and bolts of chemical calculations. As a result it is often difficult to infuse the class with timely chemistry topics. This Journal has provided some excellent applications over the years (1–8). The current government interest in nicotine conversion by cigarette companies (9) provides an example of acid–base chemistry that can be explained to students in the second college semester of general chemistry. The discussion of acid–base chemistry tends to coincide with the students’ preregistration for the next semester’s organic chemistry class. Organic chemistry has a notorious reputation. Thus students tend to be anxious about this future class. One result of this anxiety is that although the explanation for nicotine conversion relies on organic acid–base chemistry, the students are particularly interested because organic chemistry is already on their minds. This example is also suitable for an AP high school chemistry class, but is probably too advanced for an introductory high school course. The weak base ammonia is often added to cigarette tobacco (10). The U.S. Food and Drug Administration (FDA) has argued that this added ammonia enhances the delivery of nicotine into the smoker’s bloodstream. In contrast, tobacco companies argue that it is important to know as much as possible about nicotine chemistry in order to provide smoker satisfaction, and this knowledge is the underlying reason for their interest in ammonia as an additive (11). The Structure of Nicotine
H+ +
N H
CH3
(2)
CH3
Methylpyrrolidine
When pyridine and methylpyrrolidine are bonded together the new molecule is called nicotine. Nicotine occurs in a +2 form (1) when the nitrogens in both rings are protonated. If only the methylpyrrolidine takes on a proton, a +1 form (2) results. If both nitrogens are free to act as a base, the freebase form occurs (3). H
H
H
+
+
N H
CH3
H
+
N H
N
N CH3
CH3 N
N
1
2
3
Why the proton bonds to the methylpyrrolidine rather than the pyridine in the +1 form is open to interpretation (12). Rather than go off on this tangent, we simply accept that the two nitrogens differ in acidity as indicated by their pKa values. When protonated, the pyridine ring with a pK1 = 3.1 at 20 °C is much more acidic than the methylpyrrolidine ring with pK2 = 8.0 at 20 °C. The Nicotine–Ammonia Reaction
Nicotine is composed of two ring structures. One is a benzene-like structure in which one carbon is replaced by a nitrogen. This structure is called pyridine, and, in acidic solution a proton adds to the nitrogen: + H+ +
N H
N
+ N
(1)
We begin with the +2 form of nicotine. As ammonia is added, the pH increases. With reduced hydrogen ion concentration, in accordance with LeChâtelier’s principle, the pyridine ring loses its proton, changing the +2 ion to +1. As the pH approaches eight, the proton on the methylpyrrolidine ring is lost, changing the nicotine to the neutral free-base form. The fraction of the nicotine that is in free-base form is shown by Freiser (13) to be
Pyridine
The other portion of nicotine is a five-membered carbon ring with one carbon replaced by a nitrogen. The nitrogen has a methyl (– CH3) group attached to it. This molecule is called methylpyrrolidine. In acidic solution, as with pyridine, a proton adds to the nitrogen.
α=
K 1K 2 +
+ 2
(3)
K1K2 + K1 H + H
where K1 is the equilibrium constant for the loss of the first proton (from the pyridine ring), K2 is the equilibrium constant for the loss of the second proton (from the methylpyrrolidine ring), and [H+] is the hydrogen ion concentration. For our discussion the variables of interest are pH and pKa. To bring out these quantities the numerator and denominator
JChemEd.chem.wisc.edu • Vol. 76 No. 10 October 1999 • Journal of Chemical Education
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In the Classroom
of eq 3 are divided by K1K2 and then four substitutions are made:
Nicotine Variable
[H+] = 10{pH + 2
Table 1. Free-Base Nicotine as a Function of pH
{2pH
[H ] = 10
(4)
K2 = 10{pK2
pH 6
7
8
α
0.0099
0.091
0.50
Free base/+1 form
0.010
0.10
1.0
9 0.91 10
K1K2 = 10{(pK1+pK2) Equation 3 is now { pH { 2pH α = 1 + 10{ pK + 10 10 2 10 { pK 1 +pK 2
{1
(5)
In Table 1 values for eq 5 are shown for different pH values. Also, the ratio of free-base form to +1 form is calculated. From Table 1 we can see that the free-base form becomes increasingly important as the pH increases. At pH = 8, a typical pH after ammonia has been added, free-base nicotine accounts for half of the total nicotine content. The nicotine–ammonia reaction is shown in eq 6. H
H
+
+ NH3
N H N
N
CH3
+ NH4+
CH3 N
(6)
Nicotine
The free-base form is uncharged. As a result, it is able to pass through cell membranes more easily than the +1 form (14 ). Since the free-base form is more easily absorbed into the cell than the +1 form, the conversion to the free-base form using ammonia improves the delivery of nicotine to the smoker.
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The FDA’s view of the part played by ammonia in tobacco smoke is analogous to what takes place when cocaine is “freebased”. The hydrochloride salt of cocaine is mixed with aqueous ammonia. The product is the free-base form of cocaine, which is then smoked (15). Literature Cited 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12.
13. 14. 15.
Holme, T. A. J. Chem. Educ. 1994, 71, 919. Dhawale, S. W. J. Chem. Educ. 1993, 70, 395. Hecht, C. E. J. Chem. Educ. 1992, 69, 645. McCullough, T. J. Chem. Educ. 1992, 69, 543. Lisenky, G. J. Chem. Educ. 1990, 67, 562. Fulkrod, J. E. J. Chem. Educ. 1985, 62, 529. Mattice, J. J. Chem. Educ. 1983, 60, 1042. Glanville, J.; Rau, E. J. Chem. Educ. 1973, 50, 65. Raloff, J. Some Cigarette Makers Manipulate Nicotine. Science News, July 2, 1994, p 7. Kluger, R. Ashes to Ashes; Knopf: New York, 1996; pp 744–745. Food and Drug Administration. Fed. Regist. 1995, 21(Aug 11), 801–804. March, J. Advanced Organic Chemistry; Wiley Interscience: New York, 1985; pp 234–235. Katritzky, A. R. Handbook of Heterocyclic Chemistry; Pergamon: New York, 1985; p 145. Freiser, H. Concepts & Calculations in Analytical Chemistry: A Spreadsheet Approach; CRC: Boca Raton, FL, 1992; pp 60–62. Stryer, L. Biochemistry; Freeman: New York, 1988; p 284. Inciardi, J. A. In The Epidemiology of Cocaine Use and Abuse; Res. Monogr. 110; Schober S.; Schade, C., Eds.; U.S. Department of Health and Human Services: Washington, DC, 1991; p 265.
Journal of Chemical Education • Vol. 76 No. 10 October 1999 • JChemEd.chem.wisc.edu
