Ortho-Nitrotoluene

The initial indole derivatives 185 and 187 are synthesized from ortho-nitrotoluenes 191 (57CB1980 60CB2024 79JOC4003). Indolylcarboxylic... 

One of the most common photochemical reaction pathways of carbonyl compounds is the formation of a diradicaloid excited state which is able to abstract a hydrogen atom at the y (or, more rarely, e) position, followed by either fragmentation or recombination. This process, which is known as the Norrish type II reaction, has a parallel in the photochemistry of nitro groups the intramolecular hydrogen abstraction of excited ortho-nitrotoluene is actually one of the very early synthetic photochemical transformations [9]. It has been exploited in a family of photolabile protecting groups, most prominent among which are derivatives of ortho-nitrobcnzyl alcohol, as introduced in 1966 by Barltrop et al. (Scheme 13.1) [10, 11],... 

For ortho-nitrotoluene, the negative charge is localized largely in the ortho-d-d para-positions (mononitration of or /zo-nitrotoluene gives rise only to 2,6- and 2,4-dinitrotoluenes) and CTo solubility in this solvent is three times greater than that in nitrobenzene (Tables 5 and 6). 

Considering, then, the mixture of mononitrotoluenes to consist of, approximately, 38 per cent para, 4 per cent meta, and 58 per cent ortho nitrotoluene the reactions which occur on nitrating to dinitrotoluene will be investigated. 

Crystalline Form The crystalline form of the ortho nitrotoluene has evidently not been thoroughly investigated, since the various chemists do not agree upon this point. This is possibly due to the presence of both the alpha and the beta forms in the mixture. 

Preparation. The preparation of the ortho nitrotoluene is most easily carried out by the nitration of... 

A possibly better method of separating the isomeric mononitrotoluenes is. one used by the firm of Meister, Lucius Bruning. This consists in cooling the mixed nitrotoluenes to —4 to —10 °, and removing the liquid portion after about one-half the mixture has ci ystallized. The separation may be effected by a centrifuge. The liquid obtained by one crystallization is practically pure ortho nitrotoluene. The resulting mixture of meta and para nitrotoluenes may be separated by steam distillation. The para is very volatile with steam, while the meta is but slightly so. 

The sulphonation of the mononitrotoluenes offers a qualitative test for ortho nitrotoluene, in that the sulphonation product of this isomer gives no red color when boiled with sodium hydroxide. 

As an illustration of a modem and efficient route, 2,3-unsubstituted indoles are obtained from an ortho-nitrotoluene by heating with dimethylformamide dimethylacetal (DMFDMA), generating an enamine that, after reduction of the nitro group, closes with loss of dimethylamine, generating the aromatic heterocycle. 

Synonyms/Trade Names o-Methylnitrobenzene, 2-Methylnitrobenzene, ortho-Nitrotoluene, 2-Nitrotoluene ... 

This new indole ring synthesis should find utility for the preparation of 2-aryUndoles with electron-withdrawing substituents in the indole ring. Furthermore, as we see in equations 1-3, the bromine atom is impervious to attack by the Grignard reagent. The starting ortfto-nitrostilbenes were prepared in the standard fashion from the appropriate ortho-nitrotoluene and aryl aldehyde with piperidine as base. 

Problem 6.17. Based upon the pathway for para- alkylation shown in Scheme 6.95 show a similar scheme for alkylation to produce 2-nitromethylbenzene (ortho-nitrotoluene). 

The mononitration of toluene results in the formation of a mixture of the ortho, meta, and para isomers of nitrotoluene. The presence of the methyl group on the aromatic ring facilitates the nitration, but it also increases the ease of oxidation. 

If pure isomers are required, the ortho and meta compounds can be prepared by indirect methods. o-Nitrotoluene can be obtained by treating 2,4-dinitrotoluene with ammonium sulfide followed by diazotization and boiling with ethanol. / -Nitrotoluene can be prepared from -toluidine by acetylation, nitration deacetylation, diazotization, and boiling with ethanol. A fairly pure -nitrotoluene, which has been isolated from the isomeric mixture, can be purified further by repeated crystallization. 

Economic Aspects. Annual 1993 U.S. production of the mononitrotoluenes is 26,000 metric tons, with about 16,120 metric tons of the ortho isomer, 780 metric tons of the meta isomer, and 9,100 metric tons of the para isomer. The prices of (9-, m-., and -nitrotoluene in bulk fob are 1.15/kg, 2.54/kg, and 3.64/kg, respectively. The mononitrotoluenes are manufactured by Du Pont and First Chemical Corp. 

Analytical and Test Methods. o-Nitrotoluene can be analyzed for purity and isomer content by infrared spectroscopy with an accuracy of about 1%. -Nitrotoluene content can be estimated by the decomposition of the isomeric toluene diazonium chlorides because the ortho and meta isomers decompose more readily than the para isomer. A colorimetric method for determining the content of the various isomers is based on the color which forms when the mononitrotoluenes are dissolved in sulfuric acid (45). From the absorption of the sulfuric acid solution at 436 and 305 nm, the ortho and para isomer content can be deterrnined, and the meta isomer can be obtained by difference. However, this and other colorimetric methods are subject to possible interferences from other aromatic nitro compounds. A titrimetric method, based on the reduction of the nitro group with titanium(III) sulfate or chloride, can be used to determine mononitrotoluenes (32). Chromatographic methods, eg, gas chromatography or high pressure Hquid chromatography, are well suited for the deterrnination of mononitrotoluenes as well as its individual isomers. Freezing points are used commonly as indicators of purity of the various isomers. 

Three products are possible from nitration of toluene o-nitrotoluene, rw-nitro-toluene, and p-nitrotoluene. All ar e formed, but not in equal amounts. Together, the ortho-and para-substituted isomers make up 97% of the product mixture the rneta only 3%. 

Often the directing effects of substituents reinforce each other. Bromination of p-nitrotoluene, for exfflnple, takes place at the position that is ortho to the ortho, paradirecting methyl group and rneta to the meta-directing nitro group. 

C-Methylation products, o-nitrotoluene and p-nitrotoluene, were obtained when nitrobenzene was treated with dimethylsulfoxonium methylide (I)." The ratio for the ortho and para-methylation products was about 10-15 1 for the aromatic nucleophilic substitution reaction. The reaction appeared to proceed via the single-electron transfer (SET) mechanism according to ESR studies. 

X. If the directing effects of the two groups reinforce each other, the situation is straightforward. In p-nitrotoluene, for example, both the methyl and the nitro group direct further substitution to the same position (ortho to the methyl = meta to the nitro). A single product is thus formed on electrophilic substitution. 

This reaction cannot be elementary. We can hardly expect three nitric acid molecules to react at all three toluene sites (these are the ortho and para sites meta substitution is not favored) in a glorious, four-body collision. Thus, the fourth-order rate expression 01 = kab is implausible. Instead, the mechanism of the TNT reaction involves at least seven steps (two reactions leading to ortho- or /mra-nitrotoluene, three reactions leading to 2,4- or 2,6-dinitrotoluene, and two reactions leading to 2,4,6-trinitrotoluene). Each step would require only a two-body collision, could be elementary, and could be governed by a second-order rate equation. Chapter 2 shows how the component balance equations can be solved for multiple reactions so that an assumed mechanism can be tested experimentally. For the toluene nitration, even the set of seven series and parallel reactions may not constitute an adequate mechanism since an experimental study found the reaction to be 1.3 order in toluene and 1.2 order in nitric acid for an overall order of 2.5 rather than the expected value of 2. 

The ambiphilic reactivity of aromatic cation radicals, as described in Schemes 12 and 13, is particularly subtle in the charge-transfer nitration of toluene and anisole, which afford uniformly high (>95%) yields of only isomeric nitrotoluenes and nitroanisoles, respectively, without the admixture of other types of aromatic byproducts. Accordingly, let us consider how the variations in the isomeric (ortho meta para) product distributions with... 

To elevate p-selectivity in nitration of toluene is another important task. Commercial production of p-nitrotoluene up to now leads with twofold amount to the unwanted o-isomer. This stems from the statistical percentage of o m p nitration (63 3 34). Delaude et al. (1993) enumerate such a relative distribution of the unpaired electron densities in the toluene cation-radical—ipso 1/3, ortho 1/12, meta 1/12, and para 1/3. As seen, the para position is the one favored for nitration by the attack of NO (or NO2 ) radical. A procednre was described (Delande et al. 1993) that used montmorillonite clay supported copper (cupric) nitrate (claycop) in the presence of acetic anhydride (to remove excess humidity) and with carbon tetrachloride as a medinm, at room temperature. Nitrotoluene was isolated almost quantitatively with 23 1 76 ratio of ortho/meta/para mononitrotoluene. 

Metabolism and genetic toxicity have been reported to differ with the isomer of nitro-toluene. p-Nitrotoluene was not mutagenic in bacterial assays, but it did increase sister chromatid exchange frequencies and chromosomal aberrations in vitro-, in vivo it did not increase the frequency of micronuclei in bone marrow of treated rodents. Similar findings were reported for the ortho isomer, except that it did not induce chromosomal aberrations in vitro. Only the ortho isomer induces DNA excision repair in the in vivo-in vitro hepatocyte unscheduled DNA synthesis assay. Furthermore, ort/jo-nitrotoluene binds to hepatic DNA to a much greater extent than meta- or para-nitrotoluene, and investigators suggest that it may act similarly to the rodent hepatocarcino-gen 2,6-dinitrotoluene. ... 

CH3C6H5 + 2HNO3 CH3CeH4N02 + H2O + NO2 This is a fairly simple reaction to run in a flask, but the reaction is far from simple because there are in fact many minor products. [This reaction is not balanced because there are several other products.] First, there are three isomers of nitrotoluene, called ortho, meta, and para. In this reaction there is very little meta isomer, and, because of steric considerations, mostly the para nitro isomer is formed so in some sense this is a single reaction. 

Reacting ort/20-chlorotoluene with sodium in liquid ammonia generates a mixture of 67% ort/to-toluidine and 33% raeta-toluidine (Lin Krishnamurti, 1993). ortho-Toluidine can also be produeed by reduction of ort/zo-nitrotoluene or obtained mixed with / ara-toluidine by reduetion of erude nitrotoluene (Lewis, 1993). 

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