Phenols controlled nitration

Ducry and Roberge reported controlled nitration of phenol in a glass microreactor with a channel width of 500 pm and an internal volume of 2.0 ml [2]. Nitration was most efficient and controlled under nearly solvent-free conditions at 20 °C without the addition of sulfuric acid or acetic acid (Scheme 4.2). Under these concentrated conditions, autocatalysis spontaneously started in the mixing zone, allowing safe control of the reaction. Undesirable polymer formation, which is significant in batch reactions, was effectively suppressed by a factor of 10. 

Durey and Roberge reported controlled nitration of phenol in a glass microreactor with a channel width of 500 pm and an internal volume of 2.0 ml [2]. Nitration was most efficient and controlled under nearly solvent-free conditions at 20°C without... 

Authors are designed row sensitive and selective test-systems for analysis of heavy metals, active chlorine, phenols, nitrates, nitrites, phosphate etc. for analysis of objects of an environment and for control of ions Ee contents in the technological solutions of KH PO, as well as for testing some of pharmacological psychotropic daigs alkaloids (including opiates), cannabis as well as pharmaceutical preparations of phenothiazines, barbiturates and 1,4-benzodiazepines series too. 

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 ... 

The nitrosation of phenol and cresols in buffer solutions involves a diffusion-controlled C-nitrosation followed by rate-limiting proton loss. /r-Crcsol is much less reactive than the other substrates.79 Nitrosation in trifluoroacetic acid or in acetic-sulfuric acid mixtures is regioselective (e.g. 4-nitroso-m-xylene is fonned from m-xylene) and possible non-selective nitrous acid-catalysed nitration can be eliminated by purging reaction solutions with nitric oxide.80... 

The phenolic group is activating and ortho-para directing. The electrophilic substitution reactions in the nucleus in (a) nitrosation and nitration (b) halogenation and (c) acylation and alkylation, are therefore particularly facile, and various experimental procedures need to be adopted to control the extent of substitution (cf. substitution reactions of aromatic amines and their acylated derivatives, Sections 6.6.1 and 6.6.2, pp. 906 and 916 respectively). 

Nitration of phenols. Phenols can be nitrated in a two-phase system (ether-water) by NaN03(l equiv.) and HC1 (excess) in the presence of a catalytic amount of several rare earth nitrates in yields generally > 80%. The o/p ratio can be controlled to some extent by change in the acidity, but ort/io-nitration generally predominates. Aromatic hydrocarbons are not nitrated under these conditions. 

Electrophilic substitution is helped by the phenol group that acts as an activating group and directs substitution to the ortho and para positions. Sulphonation and nitration of phenols are both possible to give ortho and para substitution products. Sometimes the phenolic groups can be too powerful an activating group and it is difficult to control the reaction to one substitution, e.g., the bromination of phenol leads to 2,4,6-tribromophenol even in the absence of a Lewis acid ... 

Phenol is liable to undergo extensive oxidation during nitration so that carefully controlled conditions are required it forms 40% o- and 13% p-nitrophenolA solvent like chloroform or acetic acid is recommended. The nitration of p-cresol is carried out in benzene and acetic acid solution at 0°, the product being 3-nitro-4-hydroxytoluene (77%). The nitration of ra-cresol is discussed under method 491. Benzene is oxidized and nitrated (oxynitration) to 2,4-dinitrophenoI (72%) or to picric acid (2,4,6-trinitrophenol) by the action of mercuric nitrate in nitric acid. Aromatic alcohols like / -phenylethanol are nitrated as the esters to avoid oxidation products... 

Derivation (1) By heating phenol with dilute sulfuric acid, cooling the product, and then nitrating, keeping the temperature approximately 50C (2) by nitration with mixed acid with careful temperature control. 

The commercial dinitrophenol mixture is produced by heating phenol with dilute sulfuric acid, cooling the product, and then nitrating while keeping the temperature below 50 °C, or by nitrating with a mixed acid under careful temperature control (Sax and Lewis 1987). 2,3-, 2,5-, and 3,4-DNP are prepared by nitration of m-nitrophenol. 3,5-DNP is prepared by the replacement of one nitro group by methoxyl in 1,3,5-trinitrobenzene and demethylation of the dinitroanisole by anhydrous aluminum chloride. 2,6-DNP is prepared by sulfonation and nitration of o-nitrophenol (Harvey 1959). 2,6-DNP is also produced as a byproduct in the synthesis of 2,4-DNP by way of 2,4-dinitrochlorobenzene. 

Nitration. Nitration of phenols stopping at the mononitro or dinitro stage can be controlled with the NaN02-oxalic acid reagent system. 

The stirred flow reactor is frequently chosen when temperature control is a critical aspect, as in the nitration of aromatic hydrocarbons or glycerine (Biazzi-process). The stirred flow reactor is also chosen when the conversion must take place at a constant composition, as in the copol3rmerization of butadiene and styrene, or when a reaction between two phases has to be carried out, or when a catalyst must be kept in suspension as in the polymerization of ethylene with Ziegler catalyst, the hydrogenation of a-methylstyrene to cumene, and the air oxidation of cumene to acetone and phenol (Hercules-Distillers process). 

Virtually all nitration reactions involve electrophillic attack by nitronium ions, NO2. Consequently, reactions can be regulated by controlling the concentration of nitronium ions in solution. The conditions required for the nitration reaction vary greatly with the reactivity of the aromatic substrate. The nitration mixture required for introduction of the second nitro group into benzene to prepare dinitrobenzene and concentrated nitric and sulfuric acids at 95°C is unsuitable for dinitration of alkylated phenol because it provides the conditions for an uncontrollable exothermic reaction. The DNBP process described above was based on controlling the nitration conditions and has the advantage of having very few side reactions because it is a two-phase system with nitration reactivity based on mass transfer between phases. 

Ducry, L. and D.M. Roberge, Controlled autocatalytic nitration of phenol in a microreactor. Angewandte Chemie-Intemational Edition, 2005,44 7972-7975. 

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