Phenol, pKa

Assume that you have two unlabeled bottles, one of which contains phenol (pKa = 9.9) and one of which contains acetic acid (pKa = 4.76). in light of your answer to Problem 2.51, suggest a simple way to determine what is in each bottle. 

Solution We saw in Section 16.4 that a carbonyl group is electron-withdrawing. Thus, p-hvdroxybenzaldehyde is more acidic (pKa = 7.9) than phenol (pKa - 9.89). 

Fig. 11.4 The effect of pH on the concentration of phenol (pKa 10) and of acetic acid (pJtj 4.7) to inhibit mould growth.

Novobiocin is a weak dibasic acid with both enolic (pK 4.3) and phenolic (pKa 9.2) character, which is almost insoluble in chloroform and water at pH below 7.5 but is readily soluble in other polar organic solvents such as lower alcohols, acetone, and ethyl acetate. 

As expected, radical cations may have especially low pKa values due to their positive charge. A good example is phenol (pKa = 10) whose radical cation has a pKa value of -2 (Dixon and Murphy 1976). Here, the difference with respect to its parent is as large as 12 pK units [equilibrium (10)]. 

As can be seen from Table 4.2. most functional groups are only weak acids and/or weak bases. They are too weak to behave as acids or bases in aqueous solution and therefore are said to be neutral. There are three exceptions to this rule among the common functional groups. Carboxylic acids (p/Za 5) and substituted phenols (pKa 10) are weak acids. Amines, like ammonia, are weak bases. The pH of a 0.1 M solution of acetic acid (CH3CO2H) is about 3. Phenol is a weaker acid and the pH of a 0.1 M solution is about 5.5. And the pH of a 0.1 M solution of CH3NH2 is about 11. 

We can also make rings using alkoxide nucleophiles, and in this example the phenol (hydroxy-benzene) is deprotonated by the sodium methoxide base to give a phenoxide anion. Intramolecular attack on the conjugated ketone gives the cyclic product in excellent yield. In this case, the methoxide (pkaH about 16) will deprotonate the phenol (pKa about 10) completely, and competitive attack by MeCT acting as a nucleophile is not a problem as intramolecular reactions are usually faster than their intermolecular equivalents. 

In both cases the product would be carbonic acid ( pA = 6), which is a stronger acid than phenols (pKa — 10) but weaker than carboxylic acids (pKa — 4.5). Acid-base equilibria lie toward the weaker acid and weaker base. 

Methyl ethers are usually prepared by some variant of the Williamson ether synthesis in which an alcohol reacts with either iodomethane, dimethyl sulfate, or methyl triflate (HAZARD) in the presence of a suitable base. A word of caution dimethyl sulfate and methyl triflate, tike all powerful alkylating agents, are potentially carcinogenic and therefore should only be handled in a well-ventilated fume hood. For the 0-methylation of phenols (pKa 10) a comparatively weak base such as potassium carbonate in conjunction with dimethyl sulfate is sufficient,193 whereas simple aliphatic alcohols require stronger bases such as sodium hydride [Scheme 4.111]22 or lithium hexamethyldisilazide [Scheme 4.112].203 The latter transformation is notable for the fact that 0-methyiation was accomplished without competing elimination. 

A9.6.4.9.2 Values of log Kow can be calculated for pentachlorophenol and similar compounds, both for the ionized and unionized (neutral) forms. These values can potentially be calculated for certain reactive molecules (e.g. benzotrichloride), but the reactivity and subsequent hydrolysis also need to be considered. Also, for such ionizable phenols, pKa is a second parameter. Specific models can be used to calculate log Kow values for organometallic compounds, but they need to be applied with caution since some of these compounds really exist in the form of ion pairs in water. 

Sample problem. Is triethylamine (pKb3.24) a strong enough base to deprotonate phenol (pKa 10.0) ... 

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