CH-1 Organic Chemistry-2

1. Islamic University in Madinah Department of Chemistry CH-1Organic Chemistry-2 Alcohols Alcohols from Carbonyl Compounds Oxidation-Reduction & Organometallic Compounds Prepared By Prof Dr. Abdelfattah Haikal & Dr. Khalid Ahmad Shadid

2. Structure & Nomenclature • Alcohols have a hydroxyl (–OH) group bonded to a saturated carbon atom (sp3 hybridized) 1o 2o 3o Ethanol 2-Propanol (isopropyl alcohol) 2-Methyl- 2-propanol (tert-butyl alcohol)

4. Phenols • Compounds that have a hydroxyl group attached directly to a benzene ring

5. Ethers • The oxygen atom of an ether is bonded to two carbon atoms

6. Physical Properties ofAlcohols and Ethers • Ethers have boiling points that are roughly comparable with those of hydrocarbons of the same molecular weight (MW) • Alcohols have much higher boiling points than comparable ethers or hydrocarbons

7. For example • Alcohol molecules can associate with each other through hydrogen bonding, whereas those of ethers and hydrocarbons cannot

8. Water solubility of ethers and alcohols • Both ethers and alcohols are able to form hydrogen bonds with water • Ethers have solubilities in water that are similar to those of alcohols of the same molecular weight and that are very different from those of hydrocarbons • The solubility of alcohols in water gradually decreases as the hydrocarbon portion of the molecule lengthens; long-chain alcohols are more “alkane-like” and are, therefore, less like water

9. Physical Properties of Ethers Name Formula mp (oC) bp (oC) (1 atm)

10. Physical Properties of Alcohols Name Formula mp (oC) bp (oC) (1 atm) * * Water solubility (g/100 mL H2O)

11. Diethyl Ether • Diethyl ether is a very low boiling, highly flammable liquid • Most ethers react slowly with oxygen by a radical process called autoxidation to form hydroperoxides and peroxides

12. Step 1 Hydrogen abstraction adjacent to the ether oxygen occurs readily • Step 2

13. Step 3a A hydroperoxide • or • Step 3b Hydroperoxides and peroxides can be explosive A peroxide

14. Synthesis of Alcohols from Alkenes • Acid-catalyzed Hydration of Alkenes H⊕

15. Reactions of Alcohols • The reactions of alcohols have mainly to do with the following: • The oxygen atom of the –OH group is nucleophilic and weakly basic • The hydrogen atom of the –OH group is weakly acidic • The –OH group can be converted to a leaving group so as to allow substitution or elimination reactions

16. C–O & O–H bonds of an alcohol are polarized • Protonation of the alcohol converts a poor leaving group (HO⊖) into a good one (H2O)

17. Once the alcohol is protonated substitution reactions become possible The protonated –OH group is a good leaving group (H2O)

18. Alcohols as Acids • Alcohols have acidities similar to that of water

19. Relative Acidity H2O & alcohols are the strongest acids in this series Increasing acidity • Relative Basicity HO⊖ is the weakest acid in this series Increasing basicity

20. Conversion of Alcohols into Alkyl Halides • HX (X = Cl, Br, I) • PBr3 • SOCl2

21. Examples

22. Alkyl Halides from the Reactionof Alcohols with HydrogenHalides • The order of reactivity of alcohols • 3o • The order of reactivity of the hydrogen halides • HI > HBr > HCl • (HF is generally unreactive) > 2o > 1o < methyl

23. Mechanisms of the Reactions ofAlcohols with HX • Secondary, tertiary, allylic, and benzylic alcohols appear to react by a mechanism that involves the formation of a carbocation • Step 1

24. Step 2 • Step 3

25. Primary alcohols and methanol react to form alkyl halides under acidic conditions by an SN2 mechanism

26. Reaction of alcohols with SOCl2 • SOCl2 converts 1o and 2o alcohols to alkyl chlorides • As with PBr3, the reaction does not involve the formation of a carbocation and usually occurs without rearrangement of the carbon skeleton (especially if the temperature is kept below 0°C) • Pyridine (C5H5N) is often included to promote the reaction

27. Aldehyde Ketone Carboxylic acid Ester Amide Structure of the Carbonyl Group • Carbonyl compounds

28. The carbonyl carbon atom is sp2 hybridized; thus it and the three groups attached to it lie in the same plane. The bond angles between the three attached atoms are what we would expect of a trigonal planar structure; they are approximately 120o. • Structure The  bonding molecular orbital of formaldehyde (HCHO). The electron pair of the  bond occupies both lobes.

29. The more electronegative oxygen atom strongly attracts the electrons of both the  bond and the  bond, causing the carbonyl group to be highly polarized; the carbon atom bears a substantial positive charge and the oxygen atom bears a substantial negative charge. • Polarization and resonance structure

30. There is a large dipole moments associated with carbonyl compounds.

31. Reactions of Carbonyl Compounds with Nucleophiles One of the most important reactions of carbonyl compounds is one in which the carbonyl compound undergoes nucleophilic addition. The carbonyl group is susceptible to nucleophilic attack because, the carbonyl carbon bears a partial positive charge. As the reaction takes place, the carbon atom undergoes a change in its geometry and its hybridization state. It goes from a trigonal planar geometry and sp2 hybridization to a tetrahedral geometry and sp3 hybridization.

32. Two important nucleophiles: • Hydride ions (from NaBH4 and LiAlH4) • Carbanions (from RLi and RMgX) Primary alcohols can be oxidized to aldehydes, and aldehydes can be reduced to alcohols. [O] [H]

33. Oxidation-Reduction Reactions in Organic Chemistry • Reduction of an organic molecule usually corresponds to increasing its hydrogen content or decreasing its oxygen content oxygen content decreases hydrogen content increases aldehyde carboxylic acid

34. The opposite reaction of reduction is oxidation. • Oxidation involves Increasing the oxygen content of an organic molecule or decreasing its hydrogen content is oxidation lowest oxidation state highest oxidation state

35. Oxidation of an organic compound may be more broadly defined as a reaction that increases its content of any element more electronegative than carbon

36. Alcohols by Reduction of Carbonyl Compounds Aldehyde Primary and secondary alcohols can be synthesized by the reduction of a variety of com pounds that contain the carbonyl group. (1o alcohol) Carboxylic acid Ester (2o alcohol) Ketone

37. Lithium Aluminum Hydride • LiAlH4 (LAH) • Not only nucleophilic, but also very basic • Reacts violently with H2O or acidic protons (e.g. ROH) • Usually reactions run in ethereal solvents (e.g. Et2O, THF) • Reduces all carbonyl groups

38. Reductions of carboxylic acids are the most difficult, but they can be accomplished with the powerful reducing agent lithium aluminum hydride (LiAlH4, abbreviated LAH). It reduces carboxylic acids to primary alcohols in excellent yields.

39. Examples

40. Mechanism Esters are reduced to 1o alcohols

41. Sodium Borohydride Aldehydes and ketones can also be reduced to alcohols by hydrogen and a metal catalyst, by sodium borohydride (NaBH4) • NaBH4 • less reactive and less basic than LiAlH4 • can use protic solvent (e.g. ROH) • reduces only more reactive carbonyl groups (i.e. aldehydes and ketones) but not reactive towards esters or carboxylic acids

42. Examples

43. Mechanism (Animation) Aldehydes are reduced to 1° alcohols & ketones are reduced to 2° alcohols

44. A Mechanism for the Reaction

45. Overall Summary of LiAlH4 and NaBH4 Reactivity Reduced by LiAlH4 Reduced by NaBH4 ease of reduction

46. Problem Which reducing agent, LiAIH4 or NaBH4 would you use to carry out the following transformations?

47. 5. Organometallic Compounds • Compounds that contain carbon-metal bonds are called organometallic compounds Organometallic compounds of lithium and magnesium are of great importance in organic synthesis. Their carbon-metal bonds have considerable ionic character. The carbon atoms that is bonded to the metal atom of an organolithium or organomagnesiurn compound is a strong base and powerful nucleophile.

48. Preparation of Organomagnesium Compounds • Organomagnesium halides were discovered by the French chemist Victor Grignard in 1900. Grignard received the Nobel Prize for his discovery in 1912, and they are now called Grignard reagents in his honor. Grignard reagents have great use in organic synthesis. • Grignard reagents are usually prepared by the reaction of an organic halide and magnesium metal in an ether solvent. • Order of reactivity of RX • RI > RBr > RCl

49. Example

50. Preparation of Organomagnesium Compounds Reactions with Compounds Containing Acidic Hydrogen Atoms Grignard reagents and Organolithium compounds are very strong bases. They react with any compound that has a hydrogen attached to an electronegative atom such as oxygen, nitrogen, or sulfur.