Pharmaceutical organic chemistry II

according to PCI

1. Pharmaceutical Organic Chemistry – II Effects of substituents on Orientation of mono-substituted Benzene compounds By : Ishika Choudhary b.Pharma ; 3 rd sem. Roll no. 51 Enroll no. AJU\190857

2. Substitution in mono-substituted benzenes : All hydrogen atoms in the benzene ring are equivalent. Therefore , only one monosubstitution product (C 6 H 5 -S) is possible.

3. A second substituent, E, can occupy any of the remaining five positions : If substitution was random, proportion of disubstituted products would be : Ortho = 40% Meta = 40% Para = 20 % However this distribution is never observed actually. The proportion of products formed, in fact, is determined by the nature of the first substituent on the ring rather than on any mathematical probabilities.

4. Two types of influence of substitution : Directive or O rientation effect : the first substituent (G) may direct the next incoming substituent (E) to ortho, meta, or para position , depending on the nature of the first substituent. This is called the directive or the orientation (orient= to arrange) effect.

5. Activity effect : The substituent already present may activate or deactivate the benzene ring toward further substitution. These effects are called the Activity effects .

6. Orientation effects of mono-substituted benzene : Ortho – Para directing effect : certain substituents direct the second substituent to the ortho and para positions simultaneously. These are called ortho-para directors. Example, nitration of phenol.

7. Meta – Directing Effects : the substituents which direct the second incoming substituent primarily to the meta-position, are referred to as meta-directors. Example, nitration of nitrobenzene.

8. The key points to be remembered in this topic : The nature of groups already on an aromatic ring affect both the reactivity and orientation of future substitution. Ortho-para directors direct future substitution to the ortho and para positions. Meta directors direct future substitution to the meta position.