Very weak bases

C7HgN402. Occurs to a small extent in tea, but is chiefly prepared synthetically. Like caffeine, it is a very weak base which forms water-soluble compounds with alkalis. It has a similar pharmacological mechanism to that of caffeine and is used, in combination with ethy-lenediamine. as a diuretic and a bron-chodilator. 

Aminoazobenzene is a very weak base, and consequently it will not form salts with weak organic acids, such as acetic acid, although it will do so with the strong mineral acids, such as hydrochloric acid. Aminoazobenzene is a yellowish-brown compound, whilst the hydrochloride is steel blue. The colour of the latter is presumably due to the addition of the proton to the phenyl-N-atom, the cation thus having benzenoid and quinonoid forms ... 

On the other hand, the two nitro groups make 2,4-dinitrophenylhydrazine a very weak base, and it has therefore to be used in reasonably concentrated acid solution. 

Aniline hydrochloride, being a salt formed from a very weak base and a strong acid, undergoes considerable hydrolysis in aqueous solution to aniline... 

Determination of the dissociation constants of acids and bases from the change of absorption spectra with pH. The spectrochemical method is particularly valuable for very weak bases, such as aromatic hydrocarbons and carbonyl compounds which require high concentrations of strong mineral acid in order to be converted into the conjugate acid to a measurable extent. 

For the nitration of the very weak base, acetophenone, there is reasonable agreement between observed and calculated activation parameters, and there is no doubt that nitration of the free base occurs at acidities below that of maximum rate. In this case the equilibrium concentration of free base is much greater than in the examples just discussed and there is no question of reaction upon encounter. ... 

In dry air and in the presence of polymerisation inhibitors methyl and ethyl 2-cyanoacrylates have a storage life of many months. Whilst they may be polymerised by free-radical methods, anionic polymerisation is of greater significance. A very weak base, such as water, can bring about rapid polymerisation and in practice a trace of moisture on a substrate is enough to allow polymerisation to occur within a few seconds of closing the joint and excluding the air. (As with many acrylic monomers air can inhibit or severely retard polymerisation). 

O Connor and Cox and Yates have reviewed the many acidity function scales. A major use of acidity functions is for the measurement of the strengths of very weak bases. The procedure utilizes spectrophotometric measurements of the concentration ratio Cb/cbh+ in solutions of known acidity function and application of Eq. (8-89). One problem is the estimation of the spectra of the pure forms (protonated and unprotonated) of the base, for the spectra are subject to the medium effect, and corrections must be applied. Another problem is that the base... 

Bell has calculated Hq values with fair accuracy by assuming that the increase in acidity in strongly acid solutions is due to hydration of hydrogen ions and that the hydration number is 4. The addition of neutral salts to acid solutions produces a marked increase in acidity, and this too is probably a hydration effect in the main. Critchfield and Johnson have made use of this salt effect to titrate very weak bases in concentrated aqueous salt solutions. The addition of DMSO to aqueous solutions of strong bases increases the alkalinity of the solutions. 

Goi. As noted previously, an a-chlorine atom renders a ring-nitrogen atom very weakly basic. Cyanuric chloride (5) is a very weak base both because s-triazines are of low basicity and because each of the ring-nitrogen atoms is alpha to two chlorine atoms. Hence, this compound should be insensitive to acid catalysis or acid autocatalysis and this has been observed for the displacement of the first chlorine atom with alcohols in alcohol-acetone solution and with water (see, however. Section II,D,2,6). 

Another disadvantage found in trying to apply this technique to very weak bases (i.e. those with pA < 1) is that the neutralization of strong acid solutions forms large quantities of salt and liberates much heat, which constitutes two sources of error. 

The papaver alkaloid Narcotoline (265) can be converted into the yellow colored Cotarnoline (267) on hydrolysis which adopts a zwitterionic ground state (56MI1, 57MI1) (Scheme 87). The corresponding dihydro derivative was also identified in nature. The UV spectrum of the zwitterionic Tarkonine (268), which forms red crystals from acetone, is shifted bathochromically in comparison to the chloride. Tarkonine is a very weak base (pA b = 9.58), which is well in accord with the formation of an inner salt, and Cotarnoline (267) is a stronger base than Tarkonine (268) (pA b = 9.15). The pK values are larger than 13 (66MI3). The methylated derivative of Narcotoline is Narcotine (266). 

Quinoxalin-2-one is a very weak base (pK — 1.37) and so the different orientation of substitution in acetic and sulfuric acids may mean that in acetic acid the principal species undergoing nitration is the neutral molecule, and in sulfuric acid, the mono-cation. Treatment of quinoxaline-2,3-dione, or its iViV -dimethyl derivative in sulfuric acid, with 1 equivalent of potassium nitrate, results in nitration at position 6 with 2 equivalents of potassium nitrate, 6,7-dinitro compounds are formed. When quinoxaline is boiled with aqueous nitric acid, 6-... 

Aminopyridines, aminopyridine oxides, and 3-aminoquinoline are obviously diazotized by analogous mechanisms. Kalatzis (1967 b) studied the diazotization of 4-aminopyridine over a very large range of acid concentrations (0.0025-5.0 m HC104). This compound is comparable to 2-aminothiazole in its acid-base properties the heterocyclic nitrogen is easily protonated at pH 10, whereas the amino group is a very weak base (pKa = -6.5). Therefore, the kinetics indicate that the (mono-protonated) 4-aminopyridinium ion reacts with the nitrosyl ion. The... 

Bases that would be fully protonated in water, such as the cyclopentadienide anion,, behave as very weak bases in ammonia. 

The second problem involves the measurement of pKa values for carbonyl and thiocarbonyl derivatives. Grieg and Johnson (157) have pointed out that the measurement of pKa values for very weak bases (11) is an inaccurate and arbitrary process. Of particular difficulty for our purposes is the fact that different carbonyl derivatives may require different acidity functions. As a result of this situation, no attempt was made to make correlations of pKa data for carbonyl and thiocarbonyl derivatives with eq. (2). Because accurate pKa values can be measured for imines, these values were correlated with eq. (2), although the conformational problem remains. The imine sets were first studied by Charton and Charton (73), who correlated them with eq. (2). No correlations of data for carbonyl or thiocarbonyl derivatives with eq. (2) are extant in the literature. Bhaskar, Gosavi, and Rao (158) have reported that AG values for complex formation of substituted thioureas with iodine are a linear function of the Taft a values. Drago, Wenz, and Carlson (159) have reported similar results for complex formation between iodine and substituted amides. Oloffson (160) has reported a linear relationship between -AH for the complex of substituted N,N-dimethylamides with SbCls and the ffj constants. 

The exact reverse of the above is seen with aniline (13), which is a very weak base (pKa = 4-62) compared with ammonia (pKa = 9-25) or cyclohexylamine (pKa = 10-68). In aniline the nitrogen atom is again bonded to an sp2 hybridised carbon atom but, more significantly, the unshared electron pair on nitrogen can interact with the delocalised 7r orbitals of the nucleus ... 

Protonation, if forced upon pyrrole, is found to take place not on nitrogen but on the a-carbon atom (19). This occurs because incorporation of the nitrogen atom s lone pair of electrons into the aromatic 6jre system leaves the N atom positively polarised protons tend to be repelled by it, and are thus taken up by the adjacent a-carbon atom. The basicity situation rather resembles that already encountered with aniline (p. 70) in that the cation (19) is destabilised with respect to the neutral molecule (18a). The effect is much more pronounced with pyrrole, however, for to function as a base it has to lose all aromatic character, and consequent stabilisation this is reflected in its related pKa (-0-27) compared with aniline s of 4-62, i.e. pyrrole is a very weak base indeed. It can in fact function as an acid, albeit a very weak one, in that the H atom of the NH group may be removed by strong bases, e.g. eNH2 the resultant anion (20) then retains the aromatic character of pyrrole, unlike the cation (19) ... 

It also follows that protonation of the triazine ring makes it more susceptible to attack by nucleophilic reagents unless the reagent itself is also protonated. If the triazine ring remains unprotonated when a nucleophilic base, such as an alkylamine, is present as its acid salt the reaction is slower, of course. Cyanuric chloride itself is a very weak base that becomes protonated only under strongly acidic conditions. Thus step 1 in Scheme 11.2 can be carried out in aqueous solution even at pH 2 without risk of undesirable hydrolysis of cyanuric chloride, water being an extremely weak nucleophile. 

The conjugate bases of strong acids are very weak bases ... 

For some very weak bases, titration in water is not feasible. Using appropriate equations, explain why this would be the case for aniline, C6H5NH2, which has a ffb of 4.6 X 10-10. 

Sparingly soluble salts of primary aromatic amines are diazotised in suspension, with vigorous stirring. Very weak bases such as halo-genated anilines and nitroanilines require a large excess of acid for salt formation they are first dissolved in just sufficient hot concentrated hydrochloric acid, which is then simultaneously cooled in ice and diluted. In this way the salts, which are mostly sparingly soluble, are precipitated in a finely divided condition. Dissolution in concentrated sulphuric acid and direct diazotisation of the sulphate, precipitated as a fine powder by means of ice, is often to be recommended. The free amines, however, should never be diazotised in acid suspension because they react far too slowly. Salt formation should first be ensured. 

---