Dissolve the mixture in an organic solvent, and extract with a dilute aqueous solution of sodium hydroxide or sodium bicarbonate, which will neutralize benzoic acid.

Naphthalene remains in the organic layer, and all the benzoic acid, now converted to the benzoate salt, is in the aqueous layer. To recover benzoic acid, remove the aqueous layer, acidify it with dilute mineral acid, and extract with an organic solvent.

Using the quadratic formula to solve for y, we find that y = 0.0434 M

The alcohol product can be formed by reduction of a carboxylic acid with LiAlH₄. The carboxylic acid can be synthesized either by Grignard carboxylation or by nitrile hydrolysis. The product can also be formed by a Grignard reaction between benzyl bromide and formaldehyde.

After treating the initial alcohol with PBr₃, the same steps as used in the previous problem can be followed. A Grignard reaction between the cycloalkylmagnesium bromide and formaldehyde also yields the desired product.

Once you realize that the product results from a Grignard reaction with a nitrile, this synthesis is easy.

The positions of the carbonyl absorptions are too similar to be useful. The –OH absorptions, however, are sufficiently different for distinguishing between the compounds; the broad band of the carboxylic acid hydroxyl group is especially noticeable.

(a) p-Bromobenzoic acid is more acidic than benzoic acid because the electron-withdrawing bromine stabilizes the carboxylate anion.

(b) This p-substituted aminobenzoic acid is less acidic than benzoic acid because the electron-donating group destabilizes the carboxylate anion.

Nitrile hydrolysis can’t be used to synthesize the above carboxylic acid because the tertiary halide precursor (shown on the right) doesn’t undergo S_N2 substitution with cyanide. Grignard carboxylation also can’t be used because the acidic hydroxyl hydrogen interferes with formation of the Grignard reagent. If the hydroxyl group is protected, however, Grignard carboxylation can take place.

Nucleophilic addition (1), alkyl shift (2), and displacement of bromide (3) lead to the observed product.

The following steps take place in the Ritter reaction:

Step 1: Protonation of the alkene double bond;

Step 2: Attack of the nitrogen lone pair electrons on the carbocation;

Step 3: Attack of water on the nitrile carbon;

Step 4: Deprotonation;

Step 5: Tautomerization to the ketone.

Less basic —————> More basic

Alternatively, benzyl bromide can be converted to a Grignard reagent, poured over CO₂, and the resulting mixture can be treated with aqueous acid in the last step.

In (c), the acidic proton reacts with the Grignard reagent to form methane, for no net reaction.

As in all of these more complex syntheses, other routes to the target compound are possible. This route was chosen because the Grignard reaction introduces a double bond without removing functionality at carbon 3. Dehydration occurs in the desired direction to produce a double bond conjugated with the carboxylic acid carbonyl group.

Notice that the order of the reactions is very important. If toluene is oxidized first, the nitro group will be introduced in the meta position. If the nitro group is reduced first, oxidation to the carboxylic acid will reoxidize the –NH₂ group.

Other routes to this compound are possible. The illustrated route was chosen because it introduced the potential benzylic functional group and the potential carboxylic acid in one step. Notice that the aldehyde functional group and the cyclohexyl group both serve to direct the aromatic chlorination to the correct position. Also, reaction of the hydroxy acid with SOCl₂ converts –OH to –Cl and –CO₂H to –COCl. Treatment with H₃O⁺ regenerates the carboxylic acid.

* Electrophilic aromatic substitution

Recall from Section 20.4 that substituents that increase acidity also decrease reactivity in electrophilic aromatic substitution reactions. Of the above substituents, only –Si(CH₃)₃ is an activator.

(a) BH₃, THF, then H₂O₂, OH^–; (b) PBr₃; (c) Mg, then CO₂, then H₃O⁺ (or ^–CN, then H₃O⁺); (d) LiAlH₄, then H₃O⁺; (e) Dess–Martin periodinane, CH₂Cl₂; (f) H₂NNH₂, KOH

It is possible to assign the spectra by studying the methyl group absorptions. The methyl group peak of crotonic acid is split into a doublet by the geminal (CH₃CH=) proton, while the methyl group absorption of methacrylic acid is a singlet. The first spectrum (a) is that of crotonic acid, and the second spectrum (b) is that of methacrylic acid.

Step 1: Deprotonation.

Step 2: Decarboxylation.

Step 3: Protonation.

This reaction proceeds because of the loss of CO₂ and the stability of the enolate anion.