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.
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
- energies (steric, total, heat of formation) for the starting material,
intermediate arenium ions, and products in the nitration of toluene.
- heats of reaction for starting materials to the intermediate arenium ions
as well from the starting materials to the products.
- the electrophilic susceptibility for each ring carbon of toluene.
- the nucleophilic susceptibility of carbons possessing a positive charge
through resonance for each of the intermediate arenium ions.
- an electrophilic isodensity surface for toluene.
- a nucleophilic isodensity surface for each of the arenium ions.
- Correlate all of these findings with the observed product ratios to assess
the degree of agreement to experiment.
- Examine the data to see if they account for the lower than statistically
expected degree of ortho product.
- Ascertain whether it can be determined if nitration, under these conditions,
is governed by kinetic or thermodynamic control and whether or not the results are in
agreement with the Hammond postulate.
Note: These instructions were developed using CAChe v. 4.0 for the
Macintosh but could be easily transferred to a Windows platform.
- Draw structures for toluene, the three mononitration products, and all of the
intermediate arenium ions using the CAChe Editor.
- Keep molecules in the same orientations (plane of benzene ring) so the carbon
numbers are retained throughout.
- Watch changes in charges and hybridization when drawing the various resonance
forms for the arenium ions.
- In depicting structures, go to the VIEW menu, select "atom shape". In the
"atom shape" dialog box set the following: Display atoms as: atom label
consisting of -- element & charge, atom
number, spheres, shaded, radius: van der Waals, scale: 0.020, polyhedra scale
Project Leader Instructions
- From the Project Leader menu select a molecule or ion and analyze as
- Energy Calculations:
Set: Property of "chemical sample" using the property of "steric energy" and
the "standard procedure". Repeat this for each sample adding the properties of
"energy total" and "heat of formation".
- Susceptibility Calculations:
Set: Property of "atom" using the property of "electrophilic susceptibility"
for toluene and "nucleophilic susceptibility" for the arenium ions and the
"standard procedure". Be careful to enter the carbon atom numbers to be
evaluated ("atom number" column) manually to avoid analysis of all carbons
unless this is desired. In this experiment C1-C6 of toluene were analyzed, and
three carbons for the arenium ions generated by ortho/para attack (C2, C4, C6)
and meta attack (C1, C3, C5). The latter were the carbons that, in the
canonical resonance forms, carried positive charges. Note: these are the
assigned carbon numbers from Fig. 1.
- Evaluate isosurfaces for: "electron density"
- Click on: "HOMO and LUMO only, color frontier density, "electrophilic" when
analyzing toluene, "nucleophilic" when analyzing the arenium ions
- Set the following: grid intervals to: maximum # of 41, "preferred distance"
to 0.300 Angstroms,isosurface value: 0.010 e/A3, frontier weight = 3.00
- To get meaningful color patterns, use all molecular orbitals (from
HOMO -9999 to LUMO +9999) in MOPAC as well as in the Tabulator11.
- Do not save "planes" or "grids"
- Open the Visualizer menu
- When prompted for a molecule open the name with the ".NfonD" suffix (for
nucleophilic electron density) or the ".EfonD" suffix (for electrophilic
- Once the structure is in view (type F for Mac platform or
ctrl-F on a PC platform if it is not in view) use the track ball to scale,
rotate, or translate as necessary.
- Access the VIEW pull down menu to "surface legend". This reveals a "Color
Table" providing probability values for the color boundaries. Probability for
both electrophilic and nucleophilic attack decreases in order of the regions
colored: grey, red (0.005 at grey-red interface), yellow, green, aqua, blue, to
purple and black (0 at black-purple interface). The color scheme may be set to
- Close the "Color Table" by clicking OK.
- Again access the VIEW pull down menu to "view settings". In this submenu
adjust the "near clip" to get the visible depth at a contour slice close enough
(generally 16-18 Angstroms seemed to work good) to gain an adequate view of the
electron density. The aim is to compromise between getting too close (all
carbon atoms black or parts of the ring skeleton disappear) or too far to see
details of inner electron density. The "eye separation" was not active (grayed
out), while the "viewing distance" and "far clip" controls were not used. The
"view direction" keys (x,y,z) were also not employed.
- How does a methyl group stabilize the sigma complex?
- Are the energy calculations consistent with the known directing effect of
a methyl substituent?
- Is there a correlation between charge delocalization and sigma complex
- Are the energy calculations consistent with the Hammond postulate? Hint:
First compare energies for sigma complex formation and then energies for the
- Are the values for the heats of reaction positive or negative? Explain
- Based upon your results, is the use of nucleophilic susceptibility valid
in ascertaining localization of of positive charge in arenium ions? Why or
Extensions and Variations
- Repeat the calculations using the COSMO solvent model in MOPAC to see how
this affects calculated parameters. Explain any differences.
- Perform calculations for the nitration of t-butylbenzene.
Experimental data reveal only 16% of the ortho isomer and 73% of the para
isomer are formed2. Compare your findings and account for any
- Other comparable programs to Chem CAChe could be employed12,13
however, the outstanding spreadsheet capability provided by Project Leader
greatly expedites computation time for the multiple calculations required.
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
electrophilic and nucleophilic electron density calculations.
- Stock, L.M. "A Classic Mechanism for Aromatic Nitration" in Progr.
Phys. Org. Chem. 1976, 12, 21-47.
- Nelson, K.L. and Brown, H.C. J. Am. Chem. Soc. 1951,
- Berliner, E. Progr. Phys. Org. Chem. 1964, 2, 253.
- Ingold, C.K. "Structure and Mechanism in Organic Chemistry", 2E, Cornell
University Press, Ithaca, NY, 1969, 264-417.
- Olah, G.A. Acc. Chem. Res. 1970, 4, 240-248 and references
- Carroll, F.A. "Perspectives on Structure and Mechanism in Organic
Chemistry", 1E, Brooks/Cole (1998), pp. 513-520.
- March, J. "Advanced Organic Chemistry", 4E, John Wiley, New York, 1992, pp. 511-512.
- Hammond, G.S. J. Am. Chem. Soc. 1955, 77, 334.
- Fukui, K., Yonezawa, T. , Nagata, C. and Shingu, H. J. Chem.
Phys., 1953, 11, 1433-1442.
- Personal communication with Dr. Douglas Preston of Oxford Molecular Group,
Inc., Beaverton, OR, 13 July 1998.
- CAChe WORKSYSTEM, CAChe Reference (Ver. 3.7, 1994), p. 3-8, CAChe
Scientific, Inc. (Oxford Molecular Group, Inc.)
- Hehre, W.J., Shusterman, A. J., Huang, W. W. "A Laboratory Book of
Computational Organic Chemistry", Wavefunction, Inc., Irvine, CA, 1996, Expt. 53, pp.
- 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.
- Maron, S.H., Lando, J.B. "Fundamentals of Physical Chemistry,"
Macmillan, New York, NY, 1974, p. 274.