Carboxylic acids and derivatives

Making and reacting

• an alkylbenzene 烷基苯 (such as methylbenzene) is oxidised by hot alkaline $\text{KMnO}_4$, then dilute acid, to give benzoic acid 苯甲酸. The whole side-chain becomes a $\text{–COOH}$ group.
• a carboxylic acid reacts with $\text{PCl}_3$ and heat, $\text{PCl}_5$, or $\text{SOCl}_2$ to form an acyl chloride 酰氯.

Acids that can be oxidised further

Two carboxylic acids 羧酸 are special because they can still be oxidised:

• methanoic acid ($\text{HCOOH}$) is oxidised by Fehling's or Tollens' reagent, or acidified $\text{KMnO}_4$ / $\text{K}_2\text{Cr}_2\text{O}_7$, to carbon dioxide and water.
• ethanedioic acid ($\text{HOOCCOOH}$) is oxidised by warm acidified $\text{KMnO}_4$ to carbon dioxide.

Relative acidities

The acidity 酸性 order is:

A carboxylic acid is the strongest because, when it loses $\text{H}^+$, the negative charge is spread over two oxygen atoms, making the ion very stable. In a phenol 苯酚 the charge spreads only into the ring, and in an alcohol 醇 (giving $\text{RO}^-$) it is not spread at all.

Chlorine atoms make a carboxylic acid more acidic. Chlorine is electron-withdrawing 吸电子: through the inductive effect 诱导效应 it pulls electron density away, helping to spread the negative charge and stabilise the ion. So more chlorine atoms (closer to the $\text{–COOH}$) give a stronger acid.

An alcohol (or phenol) reacts with an acyl chloride at room temperature to give an ester 酯 and $\text{HCl}$. Examples are ethyl ethanoate (from ethanol) and phenyl benzoate (from phenol).

Acyl chlorides are made from carboxylic acids (with $\text{PCl}_3$, $\text{PCl}_5$ or $\text{SOCl}_2$). They are very reactive. At room temperature they react with:

The addition–elimination mechanism

All these reactions follow an addition–elimination 加成消去 mechanism: a nucleophile first adds to the slightly positive carbonyl carbon, then $\text{HCl}$ is eliminated. The carbonyl carbon is very $\delta+$ because two electronegative atoms, O and Cl, pull electrons away from it. Water, alcohols, ammonia and amines are neutral, but each has a lone pair on its O or N, so each can act as a nucleophile.

1. Addition. A lone pair on the O of ethanol attacks the $\delta+$ carbon. One pair of the C=O bond moves onto the O, which becomes $\text{O}^-$. The ethanol O now has three bonds and a $+$ charge. The carbon is tetrahedral 四面体形 for a moment, with four groups around it.
2. Elimination. A lone pair on the $\text{O}^-$ moves back to re-form C=O. The C–Cl bond pair goes onto the Cl, which leaves as $\text{Cl}^-$. The $\text{O}^+$ loses $\text{H}^+$, and $\text{H}^+ + \text{Cl}^-$ make $\text{HCl}$.

Swap the nucleophile and the same arrows give the other products: water gives ethanoic acid, ammonia gives ethanamide, and an amine gives an N-substituted amide. With ammonia or an amine, the $\text{HCl}$ then reacts with a second molecule of the base to form an ammonium salt.

Common mistakes.

• Drawing $\text{Cl}^-$ leaving in the first step, as if this were S$_\text{N}$1. The nucleophile adds first; Cl only leaves when the C=O re-forms.
• Starting the attacking arrow at the H of water or the alcohol. It must start at a lone pair on the O (or the N of ammonia).
• Missing the arrow that re-forms C=O, or the $+$ charge on the O (or N) of the intermediate.

Ease of hydrolysis

Compare how easily three chlorides react with water (hydrolysis 水解):

An acyl chloride reacts violently with cold water; an alkyl chloride reacts slowly; an aryl chloride (halogenoarene) does not react, because its C–Cl bond is strengthened by the ring.

Worked example. Ethanoyl chloride reacts violently with cold water, while ethyl ethanoate needs prolonged reflux with acid or alkali. Explain the difference. Both are attacked at the carbonyl carbon, so compare how open that carbon is to attack and how good the leaving group is. In ethanoyl chloride the chlorine is strongly electronegative and withdraws electrons, making the carbonyl carbon much more $\delta+$ and so far more open to a nucleophile; and $\text{Cl}^{-}$, the anion of a strong acid, is a good leaving group. In the ester the $\text{–OR}$ oxygen donates a lone pair into the carbonyl, reducing that $\delta+$ charge, and $\text{RO}^{-}$ is a poor leaving group. So the acyl chloride hydrolyses far more easily. Argue from both the $\delta+$ on the carbon and the leaving group: either one alone is usually only half the marks.

• Acyl chlorides are very reactive — learn their products with water (HCl), alcohols (esters), ammonia (amides) and amines.
• Reactivity order of derivatives: acyl chloride > ester > amide.
• Acid strength: electron-withdrawing groups (e.g. Cl) increase it — explain via the carboxylate ion.