**3. Chemistry**

### **3.1 Acidity**

An important chemical feature of phenolic compounds is the acidity of the phenol moiety. The unequal shift of electrons in the O-H bond in phenol is caused by the difference in electronegativity between H and O. The arbitrary electronegativity values according to Pauling scale are 2.1 and 3.5 respectively. Thus the formed inductive effect imparts a positive partial charge on the H atom (**Figure 23**). Thus the H atom is removable in the form of a proton by a suitable base. The pKa of phenol is 9.9, relatively stronger as an acid than aliphatic alcohols (pKa ca. 16) [13].

The resultant conjugate base, the phenoxide ion, is further stabilized by resonance (**Figure 24**). The lone pair placed as a result of proton abstraction is delocalized over the phenyl ring. Electron delocalization by resonance results in stabilization of the phenoxide ion.

Substituents on the phenol ring can have a significant effect on the acidity of phenol (**Figure 25**). For instance, electron withdrawing groups (EWG) increase the acidity of phenol. EWG stabilize the phenoxide ion further by inductive and resonance effects. On the other hand, electron donating groups (EDG) decrease the acidity of phenol. EDG lower the stability of the phenoxide ion by donating of electrons by inductive or resonance effects.

**Figure 23.**

*Acidity of phenol caused by inductive effect.*

**Figure 24.** *Resonance stabilization of the conjugate base of phenol, the phenoxide ion.*

**Figure 25.** *Effects of substituents on the acidity of phenol.* *Phenolic Compounds: Classification, Chemistry, and Updated Techniques of Analysis… DOI: http://dx.doi.org/10.5772/intechopen.98958*

For example, 4-nitrophenol with a pKa of around 7 is more acidic than phenol itself. The nitro group withdraws electrons by resonance and thus imparts an additional resonance stabilization of the phenoxide ion (**Figure 26**). Thus, 4-nitrophenoxide ion is more stable than the simple unsubstituted phenoxide ion.

For example, 4-aminophenol with a pKa of around 10.3, is less acidic than phenol itself. The nitro group imparts an additional resonance stabilization of the phenoxide ion which is then more stable than the simple unsubstituted phenoxide ion (**Figure 27**).

#### **3.2 Hydrogen bonding**

The inductive effect of the O-H bond in phenol induces a negative partial charge on O and a positive partial charge on H. Therefore, the hydrogen (H) atom can interact with heteroatoms possessing nonbonding electrons, such as O, N, F. This type of interaction is noncovalent and rather electrostatic and constitutes hydrogen-bonding (H-bonding) [14]. The H atom of the O-H bond in phenol can form a H-bond with the O atom in another phenol molecule, constituting intramolecular H-boning (**Figure 28**). In addition, the H atom is also capable of interacting with heteroatoms in other molecules to form intermolecular H-bonding.

**Figure 26.** *Resonance stabilization of the conjugate base of 4-nitrophenol.*

**Figure 28.**

*Intramolecular and intermolecular H-bonding of phenol.*

#### **Figure 29.**

*Intramolecular H-bonding of phenolic compounds.*

Phenolic compound with adjacent hydroxyl groups such as protocathechuic acid, can exhibit intramolecular H-bonding (**Figure 29**). Phenolic compounds with adjacent hydroxyl and alkoxy groups are also capable of intramolecular H-bonding.

Another structural possibility for intramolecular H-bonding is the presence of a hydroxyl group *ortho* to a carbonyl group as in butein (a chalcone type) (**Figure 30**). Another structural possibility is the presence of a hydroxyl group and a carbonyl group separated by a ring junction as in flavanone.

Intramolecular H-bonding can result in formation of five-membered rings as in Ferulic acid (**Figure 29**) and six-membered rings as in Flavanone (**Figure 30**). Such rings are inherently stable which would consequently influence the chemistry of phenolic compounds. For instance, intramolecular H-bonding can lower the solubility and reactivity of phenolic compounds in esterification and etherification reactions.

**Figure 30.** *Intramolecular H-bonding of phenolic compounds.*

*Phenolic Compounds: Classification, Chemistry, and Updated Techniques of Analysis… DOI: http://dx.doi.org/10.5772/intechopen.98958*

#### **3.3 Esterification reactions**

Phenolic compounds can take part in esterification reactions. They can contribute the phenolic hydroxyl group upon reactions with a carboxylic acid or a carboxylic acid derivative such as acid anhydrides or acid halides typified by acid chlorides (**Figure 31**), forming phenolic esters.

The other esterification possibility of phenolic compounds is for them to contribute their carboxyl group upon reactions with alcohols to produce the corresponding phenolic ester (**Figure 32**).

#### **3.4 Etherification reactions**

Phenolic compounds can undergo etherification reactions. Thus they can react with alcohols to produce the corresponding phenolic ether (**Figure 33**).

#### **3.5 Oxidation**

Phenolic compounds can undergo oxidation reactions. Homolytic (symmetrical) oxidative O-H bond cleavage gives rise to a phenolic radical (**Figure 34**). Such radicals are stabilized by resonance by delocalization of the resultant single electron over the ring.

*Etherification of phenolic compounds.*

**Figure 34.** *Oxidation of phenolic compounds to form phenolic radicals.*
