Picrates

The most versatile derivative from which the free base can be readily recovered is the picrate. This is very satisfactory for primary and secondary aliphatic amines and aromatic amines and is particularly so for heterocyclic bases. The amine, dissolved in water or alcohol, is treated with excess of a saturated solution of picric acid in water or alcohol, respectively, until separation of the picrate is complete. If separation does not occur, the solution is stirred vigorously and warmed for a few minutes, or diluted with a solvent in which the picrate is insoluble. Thus, a solution of the amine and picric acid in ethanol can be treated with petroleum ether to precipitate the picrate. Alternatively, the amine can be dissolved in alcohol and aqueous picric acid added. The picrate is filtered off, washed with water or ethanol and recrystallised from boiling water, ethanol, methanol, aqueous ethanol, methanol or chloroform. The solubility of picric acid in water and ethanol is 1.4 and 6.23 % respectively at 20 . 

It is not advisable to store large quantities of picrates for long periods, particularly when they are dry due to their potential EXPLOSIVE nature. The free base should be recovered as soon as possible. The picrate is suspended in an excess of 2N aqueous NaOH and warmed a little. Because of the limited solubility of sodium picrate, excess hot water must be added. Alternatively, because of the greater solubility of Lithium picrate, aqueous 10% lithium hydroxide solution can be used. The solution is cooled, the amine is extracted with a suitable solvent such as diethyl ether or toluene, washed with 5N NaOH until the alkaline solution remains colourless, then with water, and the extract is dried with anhydrous sodium carbonate. The solvent is distilled off and the amine is fractionally distilled (under reduced pressure if necessary) or recrystallised. 

If the amines are required as their hydrochlorides, picrates can often be decomposed by suspending them in acetone and adding two equivalents of ION HCl. The hydrochloride of the base is filtered off, leaving the picric acid in the acetone. Dowex No 1 anion-exchange resin in the chloride form is useful for changing solutions of the more soluble picrates (for example, of adenosine) into solutions of their hydrochlorides, from which sodium hydroxide precipitates the free base. 

Amines can also be purified via their salts, e.g. hydrochlorides. A solution of the amine in dry toluene, diethyl ether, dichloromethane or chloroform is saturated with dry hydrogen chloride (generated by addition of concentrated sulfuric acid to dry sodium chloride, or to concentrated HCl followed by drying the gas through sulfuric acid, or from a hydrogen chloride cylinder) and the insoluble hydrochloride is filtered off and dissolved in water. The solution is made alkaline and the amine is extracted, as above. Hydrochlorides can also be prepared by dissolving the amine in ethanolic HCl and adding diethyl ether or petroleum ether. Where 

The amine (Imol) is added to a solution of anhydrous zinc chloride (Imol) in concentrated hydrochloric acid (42mL) in ethanol (200mL, or less depending on the solubility of the double salt). The solution is stirred for Ih and the precipitated salt is filtered off and recrystallised from ethanol. The free base is recovered by adding excess of 5-ION NaOH (to dissolve the zinc hydroxide that separates) and is steam distilled. Mercuric chloride in hot water can be used instead of zinc chloride and the salt is crystallised from 1% hydrochloric acid. Other double salts have been used, e.g. cuprous salts, but are not as convenient as the above salts. 

It is not advisable to store large quantities of picrates for long periods, particularly when they are dry due to their potential EXPLOSIVE nature. Also this method is not advised when large qirantities of amines (e.g. 25g) are to be pitrified. The free base shoitld be recovered as soon as possible. The picrate is suspended in an 

Purification as their A-acetyl derivatives is satisfactory for primary, and to a hmited extent, secondary amines. Tertiary amines are not acetylated. The base is reflttxed with shghtly more than one eqirivalerrt of acetic anhydride for half to one hour, cooled and poured into ice-cold water. The insoluble derivative is filtered off, dried, and recrystallised from water, ethanol, aqueous ethanol or benzene (CAUTION toxic ). The derivative can be hydrolysed to the parent amine by refluxing with 70% sirlfuric acid for a half to one horrr. The solution is cooled, poured onto ice, and made alkaline. The amine is steam distilled or extracted as above. Alkaline hydrolysis is very slow. 

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Identification of Aromatic Hydrocarbons. Picric acid combines with many aromatic hydrocarbons, giving addition products of definite m.p. Thus with naphthalene it gives yellow naphthalene picrate, C oHg,(N08)jCeHiOH, m.p. 152°, and with anthracene it gives red anthracene picrate, C 4Hio,(NOj)jCeHjOH, m.p. 138 . For practical details, see p. 394. 

Identification of Amines. Picric acid combines with many amines to give crystalline picrates, of general formula B,(NO )aCeHjOH, where B is a molecule of a monacidic base. These picrates have usually sharp melting- or decomposition-points, and serve to characterise the amines concerned. They may be formed either by (a) direct union of the acid and the base in a suitable solvent, or (6) by the interaction of sodium picrate and a salt of the amine in aqueous solution. 

If an ethanolic solution of picric acid is similarly added to one of aniline, no precipitation occurs, owing to the high solubility of aniline picrate in ethanol. If, however, a cold aqueous solution of aniline hydrochloride is added to a similar solution of sodium picrate and the mixture shaken, yellow crystals of aniline picrate, m.p. 165 , soon separate. 

Detection of Potassium in the presence of Sodium. Add a cold saturated aqueous solution of sodium picrate to a solution of potassium chloride. A rapid precipitation of the less soluble potassium picrate occurs, even from a i°o solution of potassium chloride. 

If cold saturated ethanolic solutions of the recrystallised tetrahydrocarbazole and of picric acid are mixed and stirred, the chocolate-brown picrate of the carbazole slowly crystallises. After it has been filtered off at the pump, washed with a small quantity of ethanol, and dried, it has m.p. 145-146°. 

Dissolve a small quantity of the methiodide in cold water and add it with shaking to an excess of cold saturated aqueous sodium picrate solution. A yellow dovible salt of quinaldine niethoi icrate ami sodium picrafe. 

I or examples of other similar methopicriitcs uniting tvith picric acid or sodium picrate to livc "double piciatcs" ot larioiis stiibilifics, see b. (i. M inii... 

A) Picrates. Attempt precipitation of picrates by (a) mixing cold ethanolic solutions of the amine and of picric acid (saturated) or... 

Note. PRIMARY ALIPHATIC AMINES. The lower amines are gases or low-boiling liquids (b.ps. CHjNH, 7 CiHjNH, 17 CH,(CH2,>,NH 49 (CHg)jCHNHa, 34 ) but may be encountered in aqueous or alcoholic solution, or as their crystalline salts. They are best identified as their benzoyl, or toluene-/>-sulphonyl derivatives (c/. (C) above), and as their picrates when these are not too soluble. This applies also to benzylamine, CjHsCHjNH, b.p. 185 also to ethylenediamine, usually encountered as the hydrate, NHj (CHj)j NH2,HjO, b.p. 116 , for which a moderate excess of the reagent should be used to obtain the di-acyl derivative. (M.ps., pp. 55 55 )... 

A) Picrates (except diphenylamine). (B) Acetyl Derivatives. (C) Benzoyl, Toluene-p sulphonyl and Benzenesulphonyl Derivatives. (D)... 

Note. Secondary amines, etc. in Class (ii) can be identified by their derivatives (C) and (D) above, and by their picrates when these can be readily isolated. The preparation of derivatives (D) requires the dry amine, whereas water does not aifect that of derivatives (C). 

A) Picrates. These are usually precipitated when ethanolic solutions... 

Form picrates that of naphthalene can be readily isolated. 

Picrates. The picrates of benzene and toluene are isolated only with extreme difficulty and are not used for purposes of identification. 

Make a concentrated solution of anthracene in hot acetone. To about 2 ml. of this solution add a cold concentrated acetone solution of picric acid drop by drop, and note the formation of a red coloration which becomes deeper on further addition of the acid. If excess of picric acid is added, however, the solution becomes paler in colour, and this is to be avoided if possible. Boil to ensure that both components are in solution and then transfer to a small porcelain basin or watch-glass ruby-red crystals of anthracene picrate separate out on cooling. The product, however, is often contaminated with an excess of either anthracene or of picric acid, which appear as yellowish crystals. 

B) Picrates. Very useful for ethers containing an aromatic group. 

Primary and Secondary Amines. Picrates (pp. 374, 376), Acetyl derivatives (pp. 373, 376), Benzoyl derivatives (pp. 374, 376), Toluene-p-sulphonyl and benzene-sulphonyl derivatives (pp. 374, 376), Phenylurea derivatives (pp. 374, 377)-... 

Tertiary Amines. Picrates (p. 378), Methiodides (p. 377), />-Nitroso-deriva-tives (p. 378). 

Ethers. 3,5-Dinitrobenzoates (p. 396), Picrates (with aryl ethers) (p. 397). 

M.p. B.p. Picrate M.p. Acetyl deiiv. M.p. Benzoyl deriv. H.p. Benzene sulph. Onyl deriv. M.p. Toluene p-sulph> onyl deny. M.p. Phenyl urea deriv, M.p. 

The conversion of the compounds under investigation into coloured derivatives (e.g., the separation of carbonyl compounds by conversion into their 2 4-dinitrophenylhydrazones, etc. of hydrocarbons through their picrates of alcohols through their 3 5-dinitrobenzoates of glucose, fructose and other simple sugars through their p-phenylazobenzoyl esters). 

S-Alkyl-iso-thiuronium picrates. Alkyl bromides or iodides react with thiourea in alcoholic solution to produce S-alkyl-iso-thiuronium salts, which yield picrates of sharp melting point ... 

Place a mixture of 0-5 g. of finely powdered thiourea, 0-5 g. of the alkyl halide and 5 ml. of alcohol in a test-tube or small flask equipped with a reflux condenser. Reflux the mixture for a j)eriod depending upon the nature of the halide primary alkyl bromides and iodides, 10-20 minutes (according to the molecular weight) secondary alkyl bromides or iodides, 2-3 hours alkyl chlorides, 3-5 hours polymethy lene dibromides or di-iodides, 20-50 minutes. Then add 0 5 g. of picric acid, boil until a clear solution is obtained, and cool. If no precipitate is obtained, add a few drops of water. RecrystaUise the resulting S-alkyl-iso-thiuronium picrate from alcohol. 

Picrates of p-naphthyl alkyl ethers. Alkyl halides react with the sodium or potassium derivative of p-naphthol in alcoholic solution to yield the corresponding alkyl p-naphthyl ethers (which are usually low m.p. solids) and the latter are converted by alcoholic picric acid into the crystalline picrates ... 

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