Base, free

H2N (CH2]5 NH2. a syrupy fuming liquid, b.p. 178-180 - C. Soluble in water and alcohol. Cadaverine is one of the ptomaines and is found, associated with pulrescine, in putrefying tissues, being formed by bacterial action from the amino-acid lysine. It is found in the urine in some cases of the congenital disease cystinuria. The free base is poisonous, but its salts are not. 

Conversion of the salt of a weak base into the free base e.g.y if... 

Conversion of the salt of a weak base into the free base. Prepare a column of a strong base anion resin (such as Amberlite IRA-40o(OH) ) washed with distilled water as above. Drain off most of the water and then allow 100 ml. of A//2.Na.2C03 solution to pass through the column at 5 ml. per minute. Again wash the column with 200 ml. of distilled water. Dissolve 0-05 g. of aniline hydrochloride in 100 ml. of distilled water and pass the solution down the column. The effluent contains aniline in solution and free from all other ions. 

Phenylhydrazine is, however, frequently supplied in the form of its hydro chloride or sulphate, since these salts on exposure to light darken less rapidly than the free base. If these salts are used, however, osazone formation is unsatisfactory, partly because the mineral acid formed by hydrolysis of... 

In order to prepare the free base, place the remaining half of the crude hydrochloride in a 200 ml. beaker, add 20 ml. of water, and then stir the mixture with a glass rod until a thin paste of uniform consistency (quite free from lumps) is obtained. Now... 

A) Extract the mixture with about 40 ml. of chloroform, in which the free base is very soluble. Run off the lower chloroform layer, dry it with potassium carbonate as in (a), and then add carbon tetrachloride slowly with stirring to the filtered chloroform solution until the base starts to crystallise out. Allow to stand for a short time (t.e., until the deposition of crystals ceases) and then filter at the pump as the crystals lose the last trace of solvent, they tend as before to break up into a fine powder, the deep green colour becoming paler in consequence. 

Aldehydes and ketones may frequently be identified by their semicarbazones, obtained by direct condensation with semicarbazide (or amino-urea), NH,NHCONH a compound which is a monacidic base and usually available as its monohydrochloride, NHjCONHNH, HCl. Semicarbazones are particularly useful for identification of con jounds (such as acetophenone) of which the oxime is too soluble to be readily isolated and the phenylhydrazone is unstable moreover, the high nitrogen content of semicarbazones enables very small quantities to be accurately analysed and so identified. The general conditions for the formation of semicarbazones are very similar to those for oximes and phenylhydrazones (pp. 93, 229) the free base must of course be liberated from its salts by the addition of sodium acetate. 

When the methyl-phenyl-pyrazolone is heated with methyl iodide in methano-lie solution, it acts in the form (D), the — NH— group undergoing methy lation, with the formation of the hydriodide of 2,3-dimethyl- l-phenyl-5 Pyrazolone, or antipyrine (F), a drug used (either as the free base or as the... 

Amino-4 -methylthiazole slowly decomposes on storage to a red viscous mass. It can be stored as the nitrate, which is readily deposited as pink crystals when dilute nitric acid is added to a cold ethanolic solution of the thiazole. The nitrate can be recrystallised from ethanol, although a faint pink colour persists. Alternatively, water can be added dropwise to a boiling suspension of the nitrate in acetone until the solution is just clear charcoal is now added and the solution, when boiled for a short time, filtered and cooled, deposits the colourless crystalline nitrate, m.p. 192-194° (immersed at 185°). The thiazole can be regenerated by decomposing the nitrate with aqueous sodium hydroxide, and extracting the free base with ether as before. 

It is important not to allow the reaction mixture to become appreciably alkaline, since the free base then decomposes rapidly yielding benzyl mercaptan, which has an unpleasant odour. 

It is interesting to observe that the hydrochloride is yellow, whereas the free base is a green crystalUne compound. 

Transfer 30 g. of the hydrochloride to a 500 ml. separatory funnel, add 100 ml. of water and shake until a thin paste of uniform consistency is obtained add 10 per cent, aqueous sodium hydroxide solution in the cold with shaking until the whole mass has become bright green (the colour of the free base) and the mixture has an alkaUne reaction. Extract the free base by shaking with two 60 ml. portions of benzene (1). Dry the combined benzene extracts with a Uttle anhydrous potassium carbonate, and filter into a distiUing flask fitted with a water condenser. Distil off about half of the benzene, and pour the residual hot benzene solution into a beaker. Upon cooUng, the p-nitrosodimethylaniUne erystallises in deep green leaflets. Filter these off and dry them in the air. The yield of p-nitrosodimethylaniUne, m.p. 85°, from the hydrochloride is almost quantitative. 

Bromo-4-aminotoluene, Suspend the hydrochloride in 400 ml, of water in a 1-Utre beaker equipped with a mechanical stirrer. Add a solution of 70 g. of sodium hydroxide in 350 ml. of water. The free base separates as a dark heavy oil. After cooUng to 15-20°, transfer the mixture to a separatory funnel and run off the crude 3-bromo-4-amino-toluene. This weighs 125 g. and can be used directly in the next step (3). 

Reduction of methyl orange to />-aminodimethylaniline. Method 1. Dissolve 2 0 g. of methyl orange in the minimum volume of hot water and to the hot solution add a solution of 8 g. of stannous chloride in 20 ml. of concentrated hydrochloric acid until decolourisation takes place gentle boiling may be necessary. Cool the resulting solution in ice a crystalline precipitate consisting of sulphanilic acid and some p-aminodimethylaniline hydrochloride separates out. In order to separate the free base, add 10 per cent, sodium hydroxide solution until the precipitate of tin hydroxide redisaolves. Extract the cold solution with three or four 20 ml. portions of ether, dry the extract... 

To recover the free base, dissolve the hydrochloride in the minimum volume of boiling alcohol, add concentrated ammonia solution dropwise until a clear solution results and the blue colour has become fight brown. Add water carefully untU a cloudiness appears, warm on a water bath untU the cloudiness just disappears, and allow to cool. Yellow crystals of p-amino-azobenzene separate on coofing. 

To obtain the free base, dissolve the crude hydrochloride in 150-200 ml. of water, filter, and cool rapidly to about 20°. Pour the solution with stirring into a mixture of 150 g. of crushed ice and 50 ml. of 10 per cent, sodium hydroxide solution contained in a htre beaker. Filter oflF the... 

Phenylhydrazine may be prepared by reducing phenyldiazonium chloride solution with excess of warm sodium sulphite solution, followed by acidification with hydrochloric acid, when the hydrochloride crystallises out on cooling. Treatment of the latter with excess of sodium hydroxide solution liberates the free base. The reaction is believed to proceed through the following stages —... 

Liberate the free base by adding to the phenylhydrazine hydrochloride 125 ml. of 25 per cent, sodium hydroxide solution. Extract the phenyl-hydrazine with two 40 ml. portions of benzene, dry the extracts with 25 g. of sodium hydroxide pellets or with anhydrous potassium carbonate thorough drying is essential if foaming in the subsequent distillation is to be avoided. Most of the benzene may now be distilled under atmospheric pressure, and the residual phenylhydrazine under reduced pressure. For this purpose, fit a small dropping funnel to the main neck of a 100 ml. Claisen flask (which contains a few fragments of porous porcelain) and assemble the rest of the apparatus as in Fig. II, 20, 1, but do not connect the Perkin triangle to the pump. Run in about 40 ml. of the benzene, solution into the flask, heat the latter in an air bath (Fig. II, 5, 3) so that... 

To isolate the triphenylguanidine, dilute the residue in the flask with 50 ml. of water, add 2-3 g. of decolourising carbon, warm, and filter. Cool the solution in ice, and filter oflF the hydrochloride at the pump. Dissolve it in the minimum volume of hot water, render the solution alkaline with sodium hydroxide, and allow to cool. Filter off the free base (triphenylguanidine), and recrystallise it from alcohol it separates in colourless crystals, m.p. 144°, The yield is 3 g. 

The hydrochloride may not separate with other dialkylanilines. Add a slight excess of sodium carbonate or sodium hydroxide to the solution, extract the free base with other, etc. 

Group II. The classes 1 to 5 are usually soluble in dilute alkali and acid. Useful information may, however, be obtained by examining the behaviour of Sails to alkaline or acidic solvents. With a salt of a water-soluble base, the characteristic odour of an amine is usually apparent when it is treated with dilute alkali likewise, the salt of a water soluble, weak acid is decomposed by dilute hydrochloric acid or by concentrated sulphuric acid. The water-soluble salt of a water-insoluble acid or base will give a precipitate of either the free acid or the free base when treated with dilute acid or dilute alkali. The salts of sulphonic acids and of quaternary bases (R4NOH) are unaflFected by dilute sodium hydroxide or hydrochloric acid. 

Many aromatic compounds are sufficiently basic to be appreciably protonated in concentrated sulphuric acid. If nitration occurs substantially through the free base, then the reactivity of the conjugate acid will be negligible. Therefore, increasii the acidity of the medium will, by depleting the concentration of the free base, reduce the rateof reaction. This probably accounts for the particularly marked fall in rate which occurs in the nitration of anthraquinone, benzoic acid, benzenesulphonic acid, and some nitroanilines (see table 2.4). 

If the concentration of effective aromatic species does vary with acidity, as sometimes happens if the compound is substantially proto-nated, then the acidity-dependence of the rate will be less steep than usual, because the concentration of the active free base diminishes significantly with increasing acidity. This situation has been observed in certain cases ( 8.2). The fall in the concentration of the active species can be allowed for from a knowledge of its pK and the acidity function which, for the particular compound, gives the best measure of the acidity of the medium. Then the corrected acidity-dependence of the rate resembles that observed with compounds the concentration of which does not change significantly with acidity. The nitration of minor species is discussed later ( 8.2). 

Nitration is almost always carried out under acidic conditions. If the compound being nitrated is basic, the problem arises of deciding whether the free base or its conjugate acid is being nitrated, or if both of these species are reacting. 

Nitration may or may not involve the predominant form of the substrate. In the latter case, if the predominant form is the conjugate acid, the observed second-order rate constant can be corrected to give one (/iafb.) appropriate to the reacting free base. With a reaction of the form... 

TABLE 8.2 The acidity dependence of rates of nitration of some free bases in sulphuric acid... 

Further problems arise if measurements of the rate of nitration have been made at temperatures other than 25 °C under these circumstances two procedures are feasible. The first is discussed in 8.2.2 below. In the second the rate profile for the compound imder investigation is corrected to 25 °C by use of the Arrhenius parameters, and then further corrected for protonation to give the calculated value of logio/i fb. at 25 °C, and thus the calculated rate profile for the free base at 25 °C. The obvious disadvantage is the inaccuracy which arises from the Arrhenius extrapolation, and the fact that, as mentioned above, it is not always known which acidity functions are appropriate. 

Thus, when nitration involves a free base, a plot of logmA against — Ffo should have a slope of a (where a = HJH, but if it involves the conjugate acid the slope should be zero. 

It is found in practice that for a number of compounds reacting ma the predominant species an almost horizontal plot is obtained. For compounds presumed to be nitrated via the free bases, such as 2,6-lutidine i-oxide and 3- and 5-methyl-2-pyridone, slopes of approximately unity are obtained. Since this type of plot allows for the incomplete ionisation of nitric acid, it can be used at higher acidities than plots using — ( H + logio Hjo) which break down when the condition is no longer true. 

For a base the stoichiometric second-order rate constant which should be observed, imder conditions where ionisation to the nitronium ion is virtually complete, namely > 90 % H2SO4, if nitration were limited to the free base and occurred at every encounter with a nitronium ion, would be ... 

If the observed second-order rate constant is greater than calc., reaction via the free base is precluded. If /taobs. is less than k czlc., reaction via the conjugate acid or the free base is possible. The first compound reported to be nitrated via its conjugate acid, and yet to have 2 calc. > obs. at the acidities concerned, was pyrazoleother examples are mentioned later ( 9.3 10.4.2). 

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