Alcohols, Phenols, and Thiols in Organic Chemistry: Enhancing your Understanding of Medicinal Compounds

1. Organic chemistry for medicine and biology students Chem 2311 Chapter 7 Alcohols, Phenols and Thiols By Prof. Dr. Adel M. Awadallah Islamic University of Gaza

2. Nomencalture of alcohols Use the end ol Examples

4. Hydrogen bonding in alcohols and phenols • Alcohols and phenols form hydrogen bonds, and hence they have relatively high boiling points. This also makes the lower alcohols miscible with water. As the R group becomes larger, the solubility of alcohols in water decreases dramatically.

5. Hydrogen bonding • Hydrogen bonding occurs between molecules where you have a hydrogen atom attached to one of the very electronegative elements - fluorine, oxygen or nitrogen.

6. Acidity of Alcohols Acids are proton donors.

7. The acidity increases as the negative charge at the OH decreases (delocalized): • phenols are more acidic than Alcohols due to resonance effect (delocalization of the negative charge)

8. Nitrophenols are more acidic than phenols due to resonance and inductive effect (The partial neutralization of the negative charge by a nearby positive charge).

9. c) Electron withdrawing groups attached to alcohols increase the acidity of alcohols due to inductive effect. d) Remember; Thiols are more acidic than alcohols because the sulfur atom is larger than oxygen, and hence carries the negative charge easily.

10. Preparation of ethanol • Ethanol is manufactured by reacting ethene with steam. The catalyst used is solid silicon dioxide coated with phosphoric(V) acid. The reaction is reversible. • Only 5% of the ethene is converted into ethanol at each pass through the reactor. By removing the ethanol from the equilibrium mixture and recycling the ethene, it is possible to achieve an overall 95% conversion.

11. Making ethanol by fermentationThis method only applies to ethanol. You can't make any other alcohol this way. • Yeast is killed by ethanol concentrations in excess of about 15%, and that limits the purity of the ethanol that can be produced. The ethanol is separated from the mixture by fractional distillation to give 96% pure ethanol. • For theoretical reasons, it is impossible to remove the last 4% of water by fractional distillation.

12. The manufacture of other alcohols from alkenes Take care of Markovnikov and anti Markovnikov additions

13. Reactions of Alcohols Acidic dehydration produces alkenes with the more substituted double bond (OH- is a bad leaving group, but H2O is a good leaving group, so the reaction starts by protonation of the OH group

14. Dehydration of tertiary butyl alcohol

15. Examples

16. Reaction of Alcohols with Hydrogen Halides The general reaction looks like this: A tertiary alcohol reacts if it is shaken with concentrated hydrochloric acid at room temperature. This reaction occurs by SN1 mechanism, so the reaction rate is almost the same with HCl, HBr or HI, since the addition of the halide nucleophile occurs in the second fast step.

17. Primary Halides: The reaction is very slow with primary chlorides, and may occur by heating them with ZnCl2 for several hours. Since this reaction occurs by SN2 mechanism, the order of reactivity is: I > Br > Cl • Reaction with phosphorus(III) chloride, PCl3 • Alcohols react with liquid phosphorus(III) chloride (also called phosphorus trichloride) to make chloroalkanes.

18. Reacting alcohols with sulphur dichloride oxide (thionyl chloride) • The reaction • Sulphur dichloride oxide (thionyl chloride) has the formula SOCl2. • The two other products of the reaction (sulphur dioxide and HCl) are both gases. That means that they separate themselves from the reaction mixture. • Hydrogen halides, phosphorous halides or thionyl halides cannot replace the hydroxyl group of phenols by halogens

19. Oxidation of Alcohols Primary alcohols are oxidized to aldehydes using pyridinium chlorochromate (PCC). Oxidation by KMnO4, K2Cr2O7 or CrO3 dissolved in sulfuric acid (Jones’ reagent) gives the corresponding carboxylic acids).

20. Oxidation of secondary alcohols (gives ketones) Oxidation of tertiary alcohols (don’t occur)

21. Polyhydroxy compounds

22. Electrophilic aromatic Substitution in Phenols The hydroxyl group is an activating group. It is o, p directing group

23. Oxidation of Phenols

24. Antioxidant Phenols Phenols function as antioxidants. They destroy peroxy free radicals (ROO.)

25. Thiols Nomenclature Preparation R – X + SH- == R – SH + X-

26. Reaction of thiols with NaOH RSH + NaOH = RS- Na+ + H2O Dislfides