Proc. Natl. Acad. Sci. USA yol. 75, No. 3, pp. 1045-1049, March 1978 Chemistry Electrophilic and free radical nitration of benzene and toluene with various nitrating agents* (aromatic compounds/selectivity) GEORGE A. OLAH, HENRY C. LIN, JUDITH A. OLAH, AND SUBHASH C. NARANG Institute of Hydrocarbon Chemistry, Department of Chemistry, University of Southern California, Los Angeles, California 90007 Contributed by George A. Olah, September 29, 1977 ABSTRACT Electrophilic nitration of toluene and benzene RESULTS AND DISCUSSION was studied under various conditions with several nitrating systems. It was found that high ortlopara regioselectivity is With Nitronium Salts. Although we had previously exam- prevalent in all reactions and is independent of the reactivity ined competitive nitration using high-speed mixing (7), it was of the nitrating agent. The methyl group of toluene is predom- considered of interest to extend the studies by using more ad- inantly ortho-para directing under all reaction conditions. Steric vanced methods such as the mixing chamber of an efficient factors are considered to be important but not the sole reason Durrum-Gibson stopped-flow apparatus. Competitive nitra- for the variation in the ortho/para ratio. The results reinforce our earlier views that, in electrophilic aromatic nitrations with tions, with nitronium hexafluorophosphate in nitromethane, reactive nitrating agents, substrate and positional selectivities provided the data in Table 1. Whereas mixing still can be in- are determined in two separate steps. The first step involves a complete before reaction, with the nitration rates being very ir-aromatic-NO2 ion complex or encounter pair, whereas the fast (or reaching the encounter-controlled limit), the data seem subsequent step is of arenium ion nature (separate for the oftho, to indicate that, in the present system, both toluene and benzene meta, and para positions). The former determines substrate react by the same mechanism. In other words, if the reactions selectivity, whereas the latter determines regioselectivity. Thermal free radical nitration of benzene and toluene with indeed reach encounter-controlled limiting rates, this must be tetranitromethane in sharp contrast gave nearly statistical the case in the studied system not only for toluene but also for product distributions. benzene, accounting for the diminishing substrate selectivi- ty. Stable nitronium salts were introduced as new nitrating agents Transfer Nitrations with Nitro and Nitrito Onium Salts. by Olah and coworkers (1) in 1956. In the course of these studies Zollinger and coworkers (8) showed that addition of 2 equiva- (2-5), the competitive nitration of benzene and toluene, as well lents of water changes the substrate reactivities observed in as other aromatics, was carried out in organic solvents. nitronium salt nitrations to those conventionally observed in Under usual conditions of electrophilic nitration, toluene nitric acid solutions. A more detailed study of the competitive reacts about 20 times more rapidly than benzene whereas, with nitration of toluene and benzene in the presence of a series of nitronium salts, toluene was found to react only 1.7 times faster nucleophiles was undertaken. The results, summarized in Table than benzene (2). The practical disappearance of intermolecular 2, show that the ktoluene/kbenzene rate ratios are in the range of (substrate) selectivity was accompanied by no significant al- 2-5 when 1 equivalent of alcohol, ether, or thioether is added teration of isomer distribution (regioselectivity). This obser- but are 25-66 when 2 equivalents of the nucleophile are used. vation led to the suggestion that the transition state of highest The relative reactivity of the nitrating agent in the presence of energy (which determines substrate selectivity) is of starting added nucleophiles is in the decreasing order ROH > ROR > aromatic (i.e., 7r-complex) nature, which is then followed by RSR. The isomer distributions, however, stay similar. The data separate a-complex formation (for the individual positions), are best interpreted in terms of the nitronium ion reacting with determining positional selectivity. the n-donor nucleophile forming an 0- or S-nitronium ion in- In a series of studies, we have found that, in electrophilic termediate, which can either reverse, or transfer nitrate, or form aromatic substitutions, the position of the transition state of a covalent intermediate. R-X-R NO2Y + R-X- Y- RXNO2 + RF + PF5(BF3) Y = PF6-, BFJ-; X =0, S; R = alkyl, H. highest energy is not rigidly fixed (6) but can shift from "early" An isomer of the dimethylnitrosulfonium ion (r-complex-like) to "late" (u-complex-like) nature, depending upon the reactivity of the electrophiles and the basicity of the CH3 aromatic substrates. zS+-NO2 In order to further explore electrophilic nitration, we carried CH3 out a comprehensive study of nitration of benzene and toluene i.e., the corresponding nitrito complex, was also prepared from under various conditions. dimethyl sulfoxide and NO+. A similar nitrito complex was obtained from 4-nitropyridine-N-oxide. Both of these new ni- The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked * This paper is no. 42 in the series, "Aromatic Substitution." Paper no. "advertisement" in accordance with 18 U. S. C. §1734 solely to indicate 41 is Olah, G. A., Lin, H. C., Olah, J. A. & Narang, S. C. (1978) Proc. this fact. Nati. Acad. Sci. USA 75,545-548. 1045 Downloaded by guest on October 2, 2021 1046 Chemistry: Olah et al. Proc. Nati. Acad. Sci. USA 75 (1978) Table 1. Competitive nitration of benzene and toluene at 250 Table 3. Lewis acid halide-catalyzed Friedel-Crafts nitration of with NO'PF- in nitromethane solution (Durrum-Gibson stopped- benzene and toluene with nitryl chloride at 250 flow mixing chamber) in excess of aromatics Toluene/ Lewis acid Isomer distribution, % benzene, Isomer distribution, % halide kT/kB ortho meta para o/p mol ratio kT/kB,* ortho meta para o/p AlCl3 11.2 53 2 45 1.18 10:1 1.4 62 4 34 1.82 TiC14 17.6 53 2 45 1.18 5:1 1.4 62 3 35 1.77 BF3 25.1 57 2 41 1.39 1:1 1.7 64 3 33 1.94 SbCl5 26.7 56 2 42 1.33 1:5 2.4 64 3 33 1.94 PF5 39.3 57 2 41 1.39 1:10 2.5 63 3 34 1.85 * kT, k for toluene; kB, k for benzene. This explains the lower ortho/para' ratio observed in the Friedel-Crafts nitrations in aromatics. However, these factors trito onium ion reagents act as weak nitrating agents, requiring can decrease when the reactions are carried out in ionizing polar reaction temperatures of 550°60°. solvents such as nitromethane (Table 4). According to Ingold (9), the reactivity of a nitrating agent, Nitration with Acyl Nitrates. We have studied nitrations X-NO2, is proportional to the electron affinity of X. As a con- of toluene and benzene with a series of acyl and aroyl nitrates sequence, it is obvious that differences in species such as (11). The results summarized in Table 5 indicate some changes R2XNOZ R2tXONO, and R-X-NO2 play an important role in in substrate selectivity with only minor variations in positional these reactions. selectivity, but there is no common relationship between sub- Lewis Acid-Catalyzed Nitration with Nitryl Chloride. We strate and positional selectivities. The ktoiuene/kbenzene values have extended the study of Friedel-Crafts nitrations to an ad- increase with increasing pKa values of the corresponding acids. ditional number of Lewis acid halide catalysts (10). The data Present studies thus do not give a firm indication of the nature are shown in Table 3. With an excess of the aromatics as solvent, of the nitrating agent involved. the substrate selectivity varied from 11 to 39, accompanied by Nitration with Chloropicrin and Tetranliromethane. In slight changes in regioselectivity. Generally, the ortho/para earlier studies (7), one of us and Overchuck compared elec- ratio is lower than in nitrations with nitronium salts. trophilic with free radical nitrations-and found the latter to give In general, the kwue./k. ratio decreases with increasing nearly statistical product distributions, reflected in both sub- acidity of the catalyst. The stronger catalyst forms a more po- strate selectivity and regioselectivity. larized complex, thereby generating an early transition state. In the present studies, when tetranitromethane (12) was The complex is a bulkier nitrating agent than the nitronium mixed with benzene and toluene in ether, ethanol, nitrometh- salts, which are highly polarized in the generally used solvents ane, or pyridine/ethanol solutions, no nitration occurs up to 60°. of high dielectric constant and show no effects of ion pairing. However, when an ethereal solution of benzene/toluene (1:1) containing tetranitromethane was injected into a gas chroma- Table 2. Competitive nitration of benzene and toluene with tograph with injection block temperature of 3000, a significant NO'PF and NO+PF- in the presence of alcohofs, ethers, amount of nitro products was detected (Table 6). thioethers (sulfoxide), and N-oxide in CH3NO2 at 250 Nitroarene product composition clearly indicates that, under Isomer distribution, thermal decomposition conditions, free radical nitration is fa- Nitrating __ % vored. Low substrate selectivity (kto1uene/kbe.nzene = 0.7) is ac- agent kT/kB ortho meta para o/p companied by low positional selectivity, giving nearly statistical 40% ortho, 40% meta, and 20% para isomer distribution. NO'PF6/methanol (1:1) 3.3 63 3 34 1.85 Friedel-Crafts type nitration by tetranitromethane NO+PFj/methanol (1:2) 26.1 62- 3 35 1.77 and NOMPFe/neopentyl chloropicrin was also studied in the presence of BF3 and PF5 alcohol (1:1) 2.8 62 3 35 1.77 catalysts.