Para-nitro phenolate

So lassen sich Phenole unter extrem milden Bedingungen und einfacher Aufarbeitung mit clayfen in Tetrahydrofuran, Diethylether oder Toluol regioselektiv (keine meta-Nitro-phenole) in die cntsprechenden ortho- bzw. para-Nitro-phenole uberfuhren2 ... 

Only the aldehyde is not a commercial product and we might guess that the oxidizing power of nitric acid might convert the aldehyde into an acid. An even cheaper compound is para-nitro phenol, which can be made very easily from phenol and dilute nitric acid (Chapter 22). 

Mono-nitro Phenols.—In the first reaction the product is a mixture of ortho-nitro phenol and para-nitro phenol. The two may be easily separated as the ortho compound is volatile with steam, crystallizing in beautiful yellow crystals, while the para compound is not volatile, being left behind when the mixture is distilled with steam. It is then extracted from the residue by boiling with hydrochloric acid, recrystallized from the same solvent and obtained as fine white needles. The preparation and separation of these two compounds is a very satisfactory laboratory exercise. The meta-nitro phenol can not be pre-... 

Figure 3.2 The resonance forms of para-nitro phenolate.

Basic radicals, on the other hand, cause an overall increase in electron density on the benzenoid ring. The increase in the number of electrons in the ring would tend to produce increased activity. Thus a substance such as phenol can be nitrated very easily dilute nitric acid will produce a mixture of ortho and para nitro-phenols. Also toluene can be nitrated fourteen times as fast as benzene. 

Let us take the case of phenols and nitro-phenols. The phenoxide ion C6 H50 is colourless, but p nitro phenol is yellow, because the -N02 group in /(-position produces a yellow ion—p.N02-C6H40 . Similarly triphenylmethyl cation is colourless or pale yellow or pale yellow in acidic solution, but the corresponding ion containing two or three OH groups in para position produces deep red colour. 

A simple case where the general a constants in Table 8.5 do not succeed in correlating acidity constants is when the acid or base function is in direct resonance with the substituent. This may occur in cases such as substituted phenols, anilines, and pyridines. For example, owing to resonance (see Fig. 8.4), a para nitro group decreases the pKa of phenol much more than would be predicted from the o para constant obtained from the dissociation of p-nitrobenzoic acid. In such resonance cases (another example would be the anilines), a special set of o values (denoted as oJpara) has been derived (Table 8.5) to try to account for both inductive and resonance... 

These place a positive charge on the oxygen atom of the unionized molecule, and so cause it to repel the proton. On analysis of the experimental values for Ka at 25°C it is found that the inductive effect of a nitro group increases Ka by a factor of about 45, and the resonance effect in the ortho and para positions gives another factor of about 22. The acid constant of a nitrophenoi can be found approximately by multiplying that for phenol, l.t X 10 10, by the factor 45 for every meta nitro group and 1000 for every ortho or para nitro group in the molecule. The comparison of the values calculated in this way with those found by experiment is shown in Table 8-1. ... 

In order to reach a conclusion when and how and, and to some extent, how much of a particular insecticide was administered, the form and quantity in which the insecticide exists in different tissues and in blood and urine may give valuable clues. Indeed, an intelligent deduction is also based on the knowledge of metabolic pathways and formation of other derivatives. Thus, as parathion is excreted in the urine ultimately as p-nitro-phenol, urinary p-nitrophenol levels may indicate the extent of exposure to parathion ). In cases of mild and moderate exposure, the excreted p-nitrophenol in urine was found to be of the order of 0.057 to 0.322 mg. percent. In severe and fatal cases of poisoning by parathion, the level of p-nitrophenol in urine was from 0.16 to 1.16 mg. percent. para-Nitrophenol thus is rapidly excreted in urine and no longer detected 48 hours after the exposure to the pesticide. 

Fig. Resonance effect of a para-nitro group on a phenol.

The rearrangement occurs also when nitro benzene is electrolytically reduced by immersing the cathode in nitro benzene and sulphuric acid and the anode in sulphuric acid. Phenyl hydroxyl amine is first produced and by the above rearrangement is converted into para amino phenol. This rearrangement is analogous to the one occurring when phenyl methyl nitrosamine goes over to para-nitroso methyl aniline (P- S59)-... 

In preparing picric acid the phenol is first converted into a mixture of the ortho- and para-phenol sulphonic acid (p. 626). This by the action of concentrated nitric acid and heat yields the tri-nitro phenol. The nitro phenols are all more strongly acid than phenol itself. Picric acid is a yellow crystalline solid, m.p. 122.5°, and has a distinctly bitter taste. It forms an intensely yellow solution in water and the salts are even more strongly colored. 

Most aromatic compounds, whether of high or low reactivity, can be nitrated, because a wide variety of nitrating agents is available. For benzene, the simple alkylbenzenes, and less reactive compounds, the most common reagent is a mixture of concentrated nitric and sulfuric acids,but for active substrates, the reaction can be carried out with nitric acid alone, or in water, acetic acid, acetic anhydride, or chloroform.Nitric acid in acetic anhydride/trifluoroacetic anhydride on zeolite H-(3 was used to convert toluene to 2,4-dinitrotoluene, and AcONOi on clay converted ethylbenzene to ortho-para nitro ethylbenzene. " In fact, these milder conditions are necessary for active compounds, such as amines, phenols, and pyrroles, since reaction with mixed nitric and sulfuric acids would oxidize these substrates. With active substrates, such as amines and phenols, nitration can be accomplished by nitrosation under oxidizing conditions with a mixture of dilute nitrous and nitric acids.A mixture of N02/02/Fe(acac)3 can be used for active compounds, as can NaN02 with trichloroisocyanuric acid on wet silica gel, or N2O4 and silica acetate. Trimethoxybenzenes were nitrated easily with ceric ammonium nitrate on silica gel, and mesitylene was nitrated in an... 

An example of the second type is the separation of o- and p-nitro-phenols formed by the nitration of phenol. The ortho isomer forms an internal hydrogen bond (Fig. 1-44) which decreases its interaction with the solvent, water. The para isomer... 

The infra-red data [30a] refers to solutions in carbon tetrachloride. They show a considerable difference between ortho nitro phenols and m- and para-nitro derivatives. 

For meta- and para-substituted phenols, log values spread over 2 log units from 3-dimethylaminophenol to 4-nitro-3-trifluoromethylphenol. Their order is well explained by classical electronic effects. A dual-substituent parameter analysis gives equations 16 and 17, where crp and ctr are the Taft field-inductive and resonance substituent constants, respectively. 

The reaction of peroxynitrite (ONOO ) was also investigated with a series of para-substituted phenols in phosphate buffer solutions . The corresponding 2-nitro derivative and the 4-substituted catechol were the major products. The reaction exhibits good correlation with Hammett ap+ and half-wave reduction potentials, suggesting a... 

The reaction of phenols with nitrous acid gives the ortho- and para-nitroso products, which are formed through a neutral dienone intermediate, the proton loss from the latter being the rate-limiting step" " . It has been shown that the nitrous acid can act as a catalyst for the formation of the nitro derivatives. Thus the conventional preparation of nitro compounds by the oxidation of nitroso compounds may be replaced by methods using an electron-transfer pathway in certain cases. In the latter method, the phenoxide reacts with nitrosonium ion to give the phenoxy radical and nitric oxide radical. The nitric oxide radical is in equilibrium with the nitronium radical by reaction with nitronium ion. The reaction of the phenoxy radical with the nitroninm radical resnlts in the formation of the ortho- and para-mixo prodncts" . Leis and coworkers carried ont kinetic stndies on the reaction of phenolate ions with alkyl nitrites and fonnd that the initially formed product is the 0-nitrite ester, which evolves by a complex mechanism to give the ortho-and the para-nitro products". ... 

This latter result led us to consider that the acidity of the phenolic hydroxy groups in 27 and 28 (pKaHlO) was insufficient to promote selfelimination of the benzyl-carbamate spacer at physiological pH. Therefore, to enhance the acidity of this phenol, we prepared a second series of prodrugs, 29, 30, and 31, in which the aromatic ring of the spacer was substituted by appropriate electron-withdrawing groups, ortho-chloro (pKa=8.48), ortho-nitro (pKa=7.21), and para-nitro (pKa=7.16), respectively [61]. 

---