Product Distribution in the Nitration of Toluene

Steven W. Anderson
January 7, 1999

Notes to the Instructor: This experiment is suitable for an advanced project in the full year organic laboratory or as a project in an upper level organic course. Calculations described herein were performed using Chem CAChe. SELECTED RESULTS may be provided to students for guidance in performing their calculations. The Complete Data are available for comparison, and a separate page provides a Discussion of the complete results.

Introduction

Electrophilic aromatic substitution represents an important class of reactions in organic synthesis and is arguably the most critical transformation of arenes. The nitration of benzene and its derivatives has been extensively investigated. Nitration of toluene proceeds with predominant formation of the ortho isomer1 for which the results of Brown and Nelson2 are representative. (Fig. 1).

Figure 1 Nitration of toluene

The distribution of isomers does not appear to be altered significantly by changes in concentration of the nitrating agent2 but variation in reaction conditions can have a marked effect on product ratios3. Reported yields for the ortho isomer have ranged from 59 % (HNO3 in acetic anhydride4) to 69% (NO2+PF6- in nitromethane5). [The numbering scheme used on the benzene skeleton is referenced according to the carbon numbers assigned when the structure was drawn in the Editor of Chem CAChe.] This reaction is generally believed to proceed6 via an SEAr mechanism (Fig. 2).

Figure 2 General Scheme for the SEAr Reaction

You have learned that ortho and para attack of the nitronium ion is favored due to stabilization of specific ortho and para resonance structures via an electron-donating inductive effect of the methyl group. The regioselectivity of the final product distribution should reflect the relative stabilities of the corresponding arenium ions in accord with the Hammond postulate8.

Energy calculations for the starting material, intermediate arenium ions, and products in the nitration of toluene can be compared with the experimental data. Heats of reaction are easily inferred from these data.

ChemCAChe, and Project Leader also permit calculation of electrophilic and nucleophilic susceptibility9 for the ring carbons of toluene and the arenium ions. The electrophilic frontier density is a measure of the susceptibility of the substrate to attack by an electrophile. Electrophilic frontier density reveals reactive sites based on the electron distribution of active orbitals near the HOMO. On the other hand, the nucleophilic frontier density is a measure of the susceptibility of the substrate to attack by a nucleophile. This parameter reveals reactive sites based on the electron distribution of active orbitals near the LUMO.

Nucleophilic susceptibility may be applied to the arenium ions generated from ortho, meta or para attack of toluene by the nitronium ion. While the arenium ions are not attacked by a nucleophile per se, charge distribution might be inferred from the resultant data. Values for carbons bearing a positive charge, through resonance, indicate the degree of positive charge with the larger number reflecting a greater charge.

Finally, electron isodensity surfaces may be calculated for toluene and the various arenium ions to visually determine the most likely site for electrophilic attack on toluene and the most likely site for nucleophilic attack (i.e., the most electron deficient region) on a given arenium ion.

Objectives of this Experiment

Experimental

Note: These instructions were developed using CAChe v. 4.0 for the Macintosh but could be easily transferred to a Windows platform.

Editor Instructions

Project Leader Instructions

Tabulator Instructions

Visualizer Instructions

Questions

  1. How does a methyl group stabilize the sigma complex?

  2. Are the energy calculations consistent with the known directing effect of a methyl substituent?

  3. Is there a correlation between charge delocalization and sigma complex stability?

  4. Are the energy calculations consistent with the Hammond postulate? Hint: First compare energies for sigma complex formation and then energies for the overall reaction.

  5. Are the values for the heats of reaction positive or negative? Explain this observation.

  6. Based upon your results, is the use of nucleophilic susceptibility valid in ascertaining localization of of positive charge in arenium ions? Why or why not?

Extensions and Variations

Acknowledgement

I would like to express my sincere appreciation to Doug Preston of Oxford Molecular Group, Inc. for extensive e-mail correspondence which greatly clarified the parameters used in MOPAC, ZINDO and, in particular, the Fukui electrophilic and nucleophilic electron density calculations.

References

  1. Stock, L.M. "A Classic Mechanism for Aromatic Nitration" in Progr. Phys. Org. Chem. 1976, 12, 21-47.
  2. Nelson, K.L. and Brown, H.C. J. Am. Chem. Soc. 1951, 73, 5605-5607.
  3. Berliner, E. Progr. Phys. Org. Chem. 1964, 2, 253.
  4. Ingold, C.K. "Structure and Mechanism in Organic Chemistry", 2E, Cornell University Press, Ithaca, NY, 1969, 264-417.
  5. Olah, G.A. Acc. Chem. Res. 1970, 4, 240-248 and references cited therein.
  6. Carroll, F.A. "Perspectives on Structure and Mechanism in Organic Chemistry", 1E, Brooks/Cole (1998), pp. 513-520.
  7. March, J. "Advanced Organic Chemistry", 4E, John Wiley, New York, 1992, pp. 511-512.
  8. Hammond, G.S. J. Am. Chem. Soc. 1955, 77, 334.
  9. Fukui, K., Yonezawa, T. , Nagata, C. and Shingu, H. J. Chem. Phys., 1953, 11, 1433-1442.
  10. Personal communication with Dr. Douglas Preston of Oxford Molecular Group, Inc., Beaverton, OR, 13 July 1998.
  11. CAChe WORKSYSTEM, CAChe Reference (Ver. 3.7, 1994), p. 3-8, CAChe Scientific, Inc. (Oxford Molecular Group, Inc.)
  12. Hehre, W.J., Shusterman, A. J., Huang, W. W. "A Laboratory Book of Computational Organic Chemistry", Wavefunction, Inc., Irvine, CA, 1996, Expt. 53, pp. 175-176.
  13. Hehre, W.J., Shusterman, A.J., Nelson, J.E. "The Molecular Modeling Workbook for Organic Chemistry", Wavefunction, Inc., Irvine, CA, 1998, Expts. 4 & 5 in Chap. 13, pp. 189-190.
  14. Maron, S.H., Lando, J.B. "Fundamentals of Physical Chemistry," Macmillan, New York, NY, 1974, p. 274.

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