Nitration of phenols

The process is effected in two stages. Phenol is first sulphonated and then the sulphonation product is nitrated with nitric acid (p. 126). 

For the first stage of the process, i.e. sulphonation of phenol, sulphuric acid is used in some excess (4-4.5 moles of sulphuric acid per 1 mole of phenol). Initially a sulphuric acid ester is formed  

At room temperature the conversion proceeds slowly, whereas it occurs rapidly on heating. The higher the temperature, the more p- isomers are formed. At 90-100°C phenoldisulphonic acid is also formed  

Its presence is advisable, as later it will facilitate the nitration process. 

Marqueyrol and Loriette [1] investigated the process of phenol sulphonation with varying sulphuric acid concentration, time and temperature of sulphonation. Their results are presented below (Table 117). 

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Bright yellow needles m.p. 45 C, b.p. 2 4°C. Prepared together with 4-nitrophenol by careful nitration of phenol. Sodium sulphide reduces it to 2-aminophenol which is used in dyestuffs and photographic processes. 

In contrast to its effect upon the general mechanism of nitration by the nitronium ion, nitrous acid catalyses the nitration of phenol, aniline, and related compounds. Some of these compounds are oxidised under the conditions of reaction and the consequent formation of more nitrous acids leads to autocatalysis. 

The catalysed nitration of phenol gives chiefly 0- and />-nitrophenol, (< 0-1% of w-nitrophenol is formed), with small quantities of dinitrated compound and condensed products. The ortho para ratio is very dependent on the conditions of reaction and the concentration of nitrous acid. Thus, in aqueous solution containing sulphuric acid (i 75 mol 1 ) and nitric acid (0-5 mol 1 ), the proportion of oriha-substitution decreases from 73 % to 9 % as the concentration of nitrous acid is varied from o-i mol l i. However, when acetic acid is the solvent the proportion of ortAo-substitution changes from 44 % to 74 % on the introduction of dinitrogen tetroxide (4-5 mol 1 ). 

The theory that the catalysed nitration proceeds through nitrosation was supported by the isolation of some />-nitrosophenol from the interrupted nitration of phenol, and from the observation that the ortho.-para ratio (9 91) of strongly catalysed nitration under aqueous conditions was very similar to the corresponding ratio of formation of nitrosophenols in the absence of nitric acid. ... 

MENCKE - LASZLO Nitration ol Phenols Ortho nitration of phenols by melal nilrales Also oxidalion ot mercaptans to disuHides... 

Figure 16.14 Carbocation intermediates in the nitration of phenol. The ortho and para intermediates are more stable than the meta intermediate because of resonance donation of electrons from oxygen.

Mononitrophenols. OjN.CgH4.OH,mw 139.11, N 10.07%, OB to C02 —133.17%. Three isomers are possible but only two (o- and p-) are obtained by direct nitration. The nitration of phenol is much easier than that of aromatic hydrocarbons such as benz or toluene... 

Metafor 3- Mononitrophenol Monoclinic prisms from eth or dil HC1 mp 97° bp 194° at 70mm, decomps when distd at ordinary pressure d 1.485g/cc at 20°, 1.2797 at 100°. Does not volatilize with steam cannot be prepd by the nitration of phenol. Can be obtained by boiling diazotized m-nitroaniline with w and sulfuric acid (Ref 3). SI sol in w, sol in ale. Highly toxic by ingestion and inhalation Refs 1) Beil 6, 222-24, (116), [212-14]... 

Commercial Mononitrophenol. Yel cryst mass mp about 45° mostly ortho- with some para-nitrophenol. Can be prepd by the nitration of phenol with dil nitric acid (1 3) at a temp below 35° (see Ref, p 283). Although it does not possess expl properties and does not gelatinize NC, it has been used as the fuel component of some commercial expls. It forms salts, some of which are weak expls which were used in expl compns, for example, Voight Explosives (qv)... 

Mor alpha-) Dinitrophenol- Yel orthorhombic crysts from w, leaflets from ale mp 112—14° bp (decomp) d 1.683g/cc at 24°, 1.4829 at 72.5/4°. Sublimes when carefully heated volatile with steam. Can be prepd by the nitration of phenol, but this method is not considered commercially practicable because of partial decompn of the phenolic ring. A better method is by hydrolysis under pressure of 2,4-dinitrochloro-benzene, which in turn can be obtained by nitrating chlorobenzene. Other methods are given in Ref 1... 

Dinitrophenolsulfonic Acid f(4,6-Dinitro-phenolsulfonsaure- 2 in GerJ. Yellowish crysts. It is obtained during the prepn of PA by the sulfonation and nitration of phenol. Forms various metallic salts, such as those of Ba and K (Ref 3)... 

Tetran itro ph en oth iazine (Pheno thiazine Tetranitrosulfoxide). Yel solid, mp 368°. Can NO, H N02 be prepd in 70% yield by the nitration of phenols thiazine with a mixt of 298% nitric acid and an- hydr sulfuric acid at 60°. 

The picric acid used to make Class 2 ammonium picrate shall be made by the nitration of phenol and shall contain no material salvaged from trimmings or from loading operations. 

Class 2 ammonium picrate shall contain no reworked ammonium picrate made by way of any process other than the phenol nitration process Not applicable to ammonium picrate made from picric acid produced by the nitration of phenol... 

The color requirement is intended to cover the unavoidable presence of a small amt of the red form of Explosive D in admlxt with the yel form. The requirement with respect to irritant contaminarit -represents a control of the purity of PA used in manuf when this is made by the dinitrochlorobenzene process. The chloroform soluble impurities requirement also represents a control of the nature of impurities present in PA manufd by a process other than the nitration of phenol ... 

VII. Preparation. There are two industrial methods of manufg PA 1) nitration of Phenol 2) nitration of dinitrophenol prepd by hydrolysis of chloro dinitrobenzene... 

Certain groups attached to an aromatic ring can donate electrons into its delocalized molecular orbitals. Examples of these electron-donating substituents include —NH2 and —OH. Electrophilic substitution of benzene is much faster when an electron-donating substituent is present. For example, the nitration of phenol, C6H5OH, proceeds so quickly that it requires no catalyst. Moreover, when the products are analyzed, the only products are found to be 2-nitrophenol (ortho-nitrophenol, 37) and 4-nitrophenol (pnra-mtrophcnol, 38 . 

Today microemulsions are used in catalysis, preparation of submicron particles, solar energy conversion, extraction of minerals and protein, detergency and lubrication [58]. Most studies in the field of basic research have dealt with the physical chemistry of the systems themselves and only recently have microemulsions been used as a reaction medium in organic synthesis. The reactions investigated to date include nucleophilic substitution and additions [59], oxidations [59-61], alkylation [62], synthesis of trialkylamines [63], coupling of aryl halides [64], nitration of phenols [65], photoamidation of fluoroolefins [66] and some Diels-Alder reactions. 

The methyl ether was introduced after the Wittig reaction which used a protected carboxylic acid (ethyl ester). p-Nitrophenol is available and is one of the products of the nitration of phenol. 

Chhatre et al. (1993) have reported that highly selective ort/io-nitration of phenol with dilute nitric acid can be realized by using a microemulsion medium. It seems that in the microemulsion medium, phenol orients in such a way that the phenyl group remains extended towards the side of the organic phase, whereas the hydroxyl group protrudes in the aqueous... 

Bakke et al. (1982) have shown how montmorillonite catalyses chlorination and nitration of toluene nitration leads to 56 % para and 41 % ortho derivative compared to approximately 40 % para and 60 % ortho derivatives in the absence of the catalyst. Montmorillonite clays have an acidity comparable to nitric acid / sulphuric acid mixtures and the use of iron-exchanged material (Clayfen) gives a remarkable improvement in the para, ortho ratio in the nitration of phenols. The nitration of estrones, which is relevant in making various estrogenic drugs, can be improved in a remarkable way by using molecular engineered layer structures (MELS), while a reduction in the cost by a factor of six has been indicated. With a Clayfen type catalyst, it seems possible to manipulate the para, ortho ratio drastically for a variety of substrates and this should be useful in the manufacture of fine chemicals. In principle, such catalysts may approach biomimetic chemistry our ability to predict selectivity is very limited. 

Figure 25 Stereoselective oxidation of sulfides catalyzed by SN37.4-Ru(ToCPP) and 3A3-MP8 complexes and regioselective nitration of phenol catalyzed by 3A3-MP8.

A commonly used strategy for the higher nitration of phenolic substrates is to sulfonate the electron-rich aromatic ring before nitration. Sulfonic acid groups are electron withdrawing and... 

The nitration of phenols can result in anomalous and large differences in product isomer ratios, showing a high dependence on both nitrating agent and reaction medium. Here the situation is complicated by the intervention of an alternative nitration mechanism - that of nitrous acid catalyzed nitration, which proceeds via in situ nitrosation-oxidation (see Section 4.4). 

Direct nitration of phenol leads to excessive oxidation and destruction of material because HNO, is a strong oxidizing agent and the OH activates the ring. 

If the cation introduced by ion exchange is capable of multiple valence, the clay may serve as a catalyst for oxidation or reduction reactions. For example, montmorillonite treated with iron(III) nitrate is so reactive that it has to be stored under an inert atmosphere the clay catalyzes reactions of the nitrate ion, such as oxidation of secondary alcohols to ketones (via nitrite ester intermediates) and organic hydrazides to azides, and the nitration of phenols. 

All DD expls could be prepd either by fusing DNPh with P A or by direct nitration of phenol, dissolved in CC14, until the mixt of desired propns of DNPh PA is obtd... 

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