Nitro derivatives of cresol

Of the three isomeric cresols ortho-, meta-, and para-, only m- cresol can be used as the starting material for introducing three nitro groups, viz. in the 2,4,6-positions. Ortho and p- cresols are able to form stable nitro group systems only when no more than two nitro groups are introduced. Under the conditions of the nitration of m- cresol to its trinitro derivative the o- and p- isomers are oxidized to oxalic acid. 

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In mononitration the hazard is due to the extremely violent reaction of the unreacted hydrocarbon with the MA, and to the fact that nitro derivatives of cresols are formed in the process, along with nitro toluenes. The last stage — trinitration — is dangerous due to the drastic conditions of the reaction which requires coned acids and a high temp. The earlier method of trinitration at which temps up to 120° were applied was particularly hazardous. If the mono-nitre toluene hns not b n freed from nitro-cresols, trinitration is still more dangerous, due to the high reactivity of nitrocresols, and their liability to undergo oxidation... 

The Dinitro Methoxy Toluenes. See in Vol 3, C556-R to C557-L under Nitro Derivatives of Cresol . The CA Registry No for these compds is [50741-92-9]... 

All these factors have limited the practical application of trinitrocresol. France was the only country which used it, under the name of Cresilite mostly in mixtures with other nitro compounds to lower their melting points (Vol. III). Among nitro derivatives of cresols, dinitro-m-cresol (m. p. 86.5°C)... 

Picric acid salts Ammonium picraic Guanidine picratc Danger produced hy picraics Tctra- and pcnia-nitro derivatives of phenol Tctranitruphenol PentanitrophennI Nitro derivatives of cresols 2.4,6-T ri n i t lo-m >creso I Physical properties C hcmical properties... 

Toluene also yields nitro derivatives of o- and p- cresol besides nitrotoluenes... 

Quite a number of other high explosives were introduced during this period nitro derivatives of aniline, anisole, diphenylamine, cresols, xylenols, etc. Some of these were used as bursting charges and some as boosters, the outstanding representative of the booster explosives being trinitrophenylmethyinitramine (Tetryl). 

Other nitro-derivatives of hydrocarhons and of phenols are used in explosive mixtures. Among the former are dinitro-benzene, chlor-dinitro-benzene, dinitro-toluene, di- or tri-nitro-den-vatives of mesitylene, pseudocumene, and xylene, dinitro-naphthalene. Trinitro-naphthalene and tetra-nitro-naphthalene have also been proposed. Of the nitro-phenols, perhaps the most important is tri-nitro-cresol, known as Cresilite in France, where it is added to Melinite. Other nitro-derivatives of the aromatic series will be mentioned in the section on detonators. 

Thcrmochcmical and explosive properties Manufacture of triniiro-m-cresol Niiro derivatives of arylphcnols Nitro derivatives of 3-hydroxydiphenyl Nitro derivatives of polvhydnc phenols Dinitrorcsorcinol rnnitroresorcinol (Styphnic acid)... 

Uhde and co-workers [34, 35] have studied the migration of 4,4 -thiobis-6-tert-butyl-w-cresol (Santonex R) from plastics utensils into sunflower seed oil. Sunflower seed oil that had been stored in vessels of polyethylene containing this antioxidant was diluted (3 5) with pentane and extracted with acetonitrile containing 5 % of water. The concentrated acetonitrile extract (or an ethanol solution of the residue on evaporation) was snbjected to thin-layer chromatography on Kieselgel with hexane-ethyl acetate (10 3) as solvent. To detect the antioxidant (down to 0.1 ppm) the plate was sprayed with 3,5-dichloro-p-benzoquinonechlorimine solution. To determine the antioxidant, the zone at Rf = 0.44 (located by means of iodine vapour) was removed and treated with fuming nitric acid sulfuric acid (1 1). The nitro-derivative of the antioxidant was determined in the product by polarography after the addition of urea and sodium acetate [35],... 

The addition of mercuric nitrate is here written as a 1,4-addition, but 1,2-addition would give the same final product, and there is no evidence in the facts concerning benzene which enables us to choose between the alternative hypotheses. Toluene yields tri-nitro-m-cresol by a similar series of reactions, and it is clear that the nitro group in the addition product of mercuric nitrate and toluene has taken either the 2-, the 4-, or the 6-position, that is, one or the other of the positions activated by the methyl group. In the addition of mercuric nitrate to naphthalene, the nitro group correspondingly may be supposed to go to the active a-position. If the addition is 1,2-, the product on oxidation will yield a derivative of /J-naphthol. If it is 1,4-, it will yield a derivative of a-naphthol. The two possibilities are indicated below. 

No amino derivatives of DNOC were detected in the blood, bone marrow, or adipose tissue, but 6-amino-4-nitro-o-cresol was detected in the liver, kidneys, and brain of rabbits that received an oral dose of 18 mg/kg DNOC (Truhaut and De Lavaur 1967). No 4-amino-6-nitro-o-cresol was detected in these tissues. Both DNOC and 6-amino-4-nitro-o-cresol were recovered from the urine as 25-38% of the dose. Smaller amounts of 4-amino-6-nitro-o-cresol were also detected in the urine. Further... 

Within 2 days after receiving a single dose of 20-30 mg/kg DNOC, Chinchilla rabbits excreted <20% of the dose as metabolites (Smith et al. 1953). Unchanged DNOC accounted for 5% of the dose and conjugated DNOC accounted for 1%. Derivatives of 6-amino-4-nitro-o-cresol comprised 11-12% of the dose, including 6-acetoamido-4-nitro-o-cresol (1-1.5% of the dose), O- conjugates of this metabolite (10% of the dose), and unspecified amounts of 3-amino-5-nitro-salicylic acid and derivatives of 4-amino-6-nitro-o-cresol that were also excreted in the urine. 

Pure meto-cresol has been used for manufacture of synthetic musk— musk ambrette, used as a fixative to perfumes, for manufacture of synthetic Thymol and Menthol amd also leather preservative p-chloro-meto-cresol, synthetic pyre-throids, and lastly for manufacture of 2,3,6-trimethylphe-nol—an intermediate for vitamin E. o-Cresol has been used for manufacture of Coumarin and some derivatives which are employed in perfumery as fixative. o-Cresol has also been used for making Novolac and epoxy resins and also for the herbicides based on di-nitro-oAt/io-cresol, etc. In sum, individual cresols have been very successfully converted to important intermediates in the organic chemical synthesis. It is expected that further development work will lead to synthesis of many more organic chemicals of vital importance. While new chemicals using individual cresols are in the pipeline... 

Rat cecal contents were incubated with DNOC to determine whether the compound is metabolized in the large intestine (Ingebrigtsen and Froslie 1979). About 80% of DNOC was metabolized to 6-amino-4- nitro-o-cresol within 1 hour. Within the next 12 hours, 90% of this metabolite was further reduced to 2-methyl-4,6-diaminophenol. The authors determined that the cecal microorganisms in rats were responsible for the reduction of DNOC and its subsequent metabolites to diamino derivatives. Although not detected in humans or other monogastrics, these diamino derivatives are formed in sufficient quantities in ruminants to cause methemoglobinemia, which can be fatal in these species (Froslie 1973). 

Harvey DG. 1953. The toxicity of the dinitro-cresols Part II The formation and toxic properties of some nitro compounds derived from meta-and para-cresols. J Pharm Pharmacol 5 497-510. 

In the direct nitration of o-cresol a mixture of the p- and o- derivatives is formed, from which relatively little of the para- isomer can be isolated.1 Better methods for the preparation of the />ara-compound are by diazotization of 5-nitro-o-toluidine and replacement of the diazo group by hydroxyl, or by simply boiling the nitrotoluidme with strong aqueous alkali.1... 

Derivation 2-Nitro-p-cresol, obtained by the action of nitrous and excess nitric acids uponp-toluidine, is methylated and reduced. 

Three patents issued in 1924 and 1925 are conspicuous as placing special emphasis upon the preparation of particular catalysts as suitable for reactions involving the partial oxidation of side chains present in aromatic nuclei. The first00 of these relates to the oxidation of aromatic hydrocarbons and their derivatives, viz., toluene, xylene, cymene, cumene, mesitylene, cresols, etc., together with their derivatives including nitro-... 

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