# Which is easier, the nitration of toluene or the nitration of mesitylene (1,3,5-trimethylbenzene)?

Does the toluene can undergo nitration easier than mesitylene (1,3,5-trimethylbenzene), due to the high repulsion that will occur between $$\ce{NO2}$$ and the two adjacent methyl groups (in mesitylene nitration case)?

• What do you mean by easier? Sufficiency of mild conditions? Faster reaction? – William R. Ebenezer Apr 10 '19 at 16:13
• In case of mesitylene one needs to be careful not to oxidize methyl groups - they aren't enough to prevent nitration, but compound is vulnerable to oxidation of side groups. – Mithoron Apr 11 '19 at 18:19

The kinetics of aromatic nitration depend on the nitrating method, which also bear directly or indirectly on the subject of nitration. For example, aromatic nitration displays second-order kinetics in sulphuric acid (when used in nitrating mixture), and first-order kinetics in nitric acid. Aromatic nitration also displays first-order kinetics in either nitromethane or acetic acid (when used as a solvent) with nitric acid in constant excess. It exhibits zeroth-order kinetics for sufficiently reactive aromatic compounds, and first-order kinetics for sufficiently unreactive compounds used for nitration (Ref.1). The reference predicts that:

The numerical results vary with the conditions, but are not very sensitive to them; so that the following statements may be taken as approximately true over a considerable range of temperatures and nitrating media. Toluene is attacked 24 times faster than benzene, fluoro- and iodo-benzene 6 times more slowly than benzene, chloro- and bromo-benzene 30 times more slowly than benzene, and ethyl benzoate 300 times more slowly than benzene. Qualitatively we know that benzenesulphonic acid is attacked still more slowly, and nitrobenzene even more slowly. Thus the relative effects of substituents in activating or deactivating the benzene nucleus towards this type of attack is expressed by the following sequence: $$\ce{Me > (H) > F, I > Cl, Br > CO2Et > SO3H > NO2}$$

Thus, it is fair to conclude that the nitration of mesitylene is faster than that of toluene regardless of the steric effects enforced by neighboring 1,3-dimethyl functions. That conclusion is confirmed by the relative rates listed in Ref.1 & 2 where it is the case in all conditions considered (obs. rates are at $$\pu{25 ^{\circ}C}$$):

$$\begin{array}{|c|c|c|c|c|c|} \hline \textrm{Compound} & 7.5\% \: \textrm{aq.} & 15\% \: \textrm{aq.} & 61.01\% \: \textrm{aq.} & 68.3\% \: \textrm{aq.} & \textrm{Estimated} \\ \textrm{nitrated} & \textrm{Sulfolane} & \ce{CH3NO2} & \ce{HClO4} & \ce{H2SO4} & \textrm{Rel. Rate} \\ \hline \textrm{Benzene} & 1 & 1 & 1 & 1 & 1 \\ \hline \textrm{Toluene} & 20 & 25 & 19 & 17 & 23 \\ \hline \textrm{p-Xylene} & 114 & 130 & 84 & 38 & 50 \\ \hline \textrm{m-Xylene} & 100 & 146 & - & 38 & 400 \\ \hline \textrm{Mesitylene} & 350 & 400 & 78 & 36 & 16000 \\ \hline \end{array}$$ Estimated relative rates are from reference 3 (the authors have calculated from the observed value for toluene and the known isomer ratios by assuming the additivity principle).

References:

1. E. D. Hughes, C. K. Ingold, R. I. Reed, “493. Kinetics and mechanism of aromatic nitration. Part II. Nitration by the nitronium ion, $$\ce{NO2^+}$$, derived from nitric acid,” J. Chem. Soc. 1950, 2400–2440 (DOI: 10.1039/JR9500002400).
2. J. G. Hoggett, R. B. Moodie, J. R. Penton, K. chofield, In Nitration and aromatic reactivity; Cambridge University Press: London, United Kingdom, 1971, “Chapter 3: Nitrating Systems: B. Inert organic solvents,” pp. 32–49.
3. R. G. Coombes, R. B. Moodie, K. chofield, “Electrophilic aromatic substitution. Part I. The nitration of some reactive aromatic compounds in concentrated sulphuric and perchloric acids,” Journal of the Chemical Society B: Physical Organic 1968, 800–804 (DOI: 10.1039/J29680000800).