Liebermann reaction

Note. The nitrosamines in Class (ii) do not give the Liebermann reaction. 

The Liebermann Reaction.—Dissolve a small amount of nitrosophenol in a little molten phenol and add concentrated sulphuric acid. A magnificent cherry-red colour is obtained when the melt is diluted with water and alkali is added the colour changes to blue. 

Since phenol is converted to nitrosophenol by nitrous acid, even when the latter is combined in the form of the NO-group, labile nitroso-groups may he detected by the Liebermann reaction. 

In these cases it is usually possible to explain why the color is formed. The reactions can be further classified, on the basis of the type of colored compound formed, into reactions leading to the formation of azo dyes, di- or triphenylmethane dyes, xanthene dyes, polymethine dyes, indophenols, etc. Azo dyes are formed, for example, in the reaction of diazonium salts and phenols (p. 192) or amines (p. 324), azomethines in the reaction of primary aromatic amines with aromatic aldehydes (p. 215), di- and triphenylmethane dyes in the reaction of aromatic aldehydes with aromatic hydrocarbons in concentrated sulfuric acid (p. 213), triphenylmethane dyes in the reaction of phenols with aromatic aldehydes or oxalic acid (p. 196), xanthene dyes in the reaction of anhydrides of dicarboxylic acids with resorcinol (p. 196), polymethine dyes are formed after the cleavage of the pyridine ring in the reaction of the glutaconaldehyde formed and barbituric acid (p. 378), indophenols on reaction of phenols with Gibbs reagent (p. 195), or 4-aminoantipyrine according to Emerson (p. 194), or on the Liebermann reaction (p. 195). 

The Liebermann reaction can also be used, as in the case of nitroso compounds. This reaction is also given by nitramines—compounds with the groupings... 

Asymmetrically substituted hydrazines can be converted to N-nitro-soamines by reaction with nitrous acid. They can be detected by using the Liebermann reaction (p. 195). 

Among other color reactions of thiophene, the following may be mentioned Liebermann reaction with nitrite and sulfuric acid (73) the very sensitive reaction with thaline (tetrahydro-/ -hydroxyquinoline methyl ether) and dilute nitric acid (74) reaction with sulfuric acid, copper (II) acetate, and lactic acid (75) and, especially, the reaction with ceric ammonium nitrate (76). Of course, this reaction is not specific (see also p. 170), but it allows the differentiation of isomeric thiophene derivatives. 

Reaction of Diphenylnitrosoamine. Carry out Liebermann s Nitroso Reaction as described for phenol (p. 340), but use about 0 05 g. of the nitrosamine instead of the one crystal of sodium nitrite, and finally add only 3-4 drops of sulphuric acid. The deep greenish-blue colour is obtained, becoming red on dilution and reverting to blue on being made alkaline. 

Reactions, (i) ) >-Nitrosodimethyianiline docs not give Liebermann s Nitroso Reaction with phenol and sulphuric acid (see footnote, p. 340). 

Certain phenols give the Liebermann Nitroso Reaction. 

Formation of nitrosaminey RgN NO. (a) From monomethylaniline. Dissolve I ml. of monomethylaniline in about 3 ml. of dil. HCl and add sodium nitrite solution gradually with shaking until the yellow oil separates out at the bottom of the solution. Transfer completely to a smdl separating-funnel, add about 20 ml. of ether and sh e. Run off the lower layer and wash the ethereal extract first with water, then with dil. NaOH solution, and finally with w ter to free it completely from nitrous acid. Evaporate the ether in a basin over a previously warmed water-bath, in a fume cupboard with no flames near. Apply Liebermann s reaction to the residual oil (p. 340). 

Dissolve 1 g. of the secondary amine in 3-5 ml. of dilute hydrochloric acid or of alcohol (in the latter case, add 1 ml. of concentrated hydrochloric acid). Cool to about 5° and add 4-5 ml. of 10 per cent, sodium nitrite solution, and allow to stand for 5 minutes. Add 10 ml. of water, transfer to a small separatory funnel and extract the oil with about 20 ml. of ether. Wash the ethereal extract successively with water, dilute sodium hydroxide solution and water. Remove the ether on a previously warmed water bath no flames should be present in the vicinity. Apply Liebermann s nitroso reaction to the residual oil or solid thus. Place 1 drop or 0 01-0 02 g. of the nitroso compovmd in a dry test-tube, add 0 05 g. of phenol and warm together for 20 seconds cool, and add 1 ml. of concentrated sulphuric acid. An intense green (or greenish-blue) colouration will be developed, which changes to pale red upon pouring into 30-50 ml. of cold water the colour becomes deep blue or green upon adding excess of sodium hydroxide solution. 

The p-nitroso compounds do not give Liebermann s nitroso reaction. 

Some reference to the use of nitrous acid merits mention here. Primary aromatic amines yield diazonium compounds, which may be coupled with phenols to yield highly-coloured azo dyes (see Section IV,100,(iii)). Secondary aromatic amines afford nitroso compounds, which give Liebermann a nitroso reaction Section IV,100,(v). Tertiary aromatic amines, of the type of dimethylaniline, yield p-nitroso derivatives see Section IV,100,(vii). ... 

In 1891, Miolati (75) confirmed the cyclic formula of Liebermann and Lange by preparing the compound by three new pathways (1) reaction of CS2 on thiohydantoin, (2) condensation of ammonium dithiocarbamate with chloroacetic ester, (3) reaction of HjS on thiocyanoacetic acid. 

The earliest preparation of cellulose acetate is credited to Schiitzenberger in 1865. The method used was to heat the cotton with acetic anhydride in sealed tubes at 130-140°C. The severe reaction conditions led to a white amorphous polymer but the product would have been severely degraded and the process difficult to control. Subsequent studies made by Liebermann, Francimont, Miles, the Bayer Company and by other workers led to techniques for controlled acetylation under less severe conditions. 

The presence of a nitmso-coinpound may be detected as follows. Melt together a niiniite quantity of nitrosophenol and a few crystals of [ilienol. Add ahout 2 c.c. concentrated sulphuric acid and waiin ciy gently. A blue solution is obtained, which changes to red on dilution with water, and back to blue on adding alkali (Liebermann s nitioso reaction sec Reaction, p. 180). Sec AppL Hiiix, ]). 280. 

The action of bromine water (p. 180), Liebermann s nitroso-reaction (p. 180) and the phenolphthalein reaction (p. 186), using rone, sulphuric acid or zinc chloride, may also be applied. 

In the case of a secondary base, the above treatmemt with hydrochloric acid and sodium nitrite will give an insoluble nitrosaminc (licpiid or solid), which is frcc(ueutly 3 cllow. It may be separated by ether tind, after removing the ether, tested l y Liebermann s nitroso-reaction (sec Reaction 3, p. 159). Niti Sus. acid has no action on tertiary aliphatic amines, hut fornrs nitroso-... 

Table 2. Prevalence of symptoms in anaphylactic reactions according to Przybilla and Rueff [see 18]. A meta-analysis of 1,865 cases from 14 publications (Liebermann) and 865 own patients with insect venom anaphylaxis... 

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