Syntheses and Interconversions of Organic Compounds

1. Chapter 37 Syntheses and Interconversions of Organic Compounds 37.1Planning Organic Syntheses 37.2Interconversions of Functional Groups of Organic Compounds 37.3Chain Lengthening or Shortening of Carbon Skeleton

2. 37.1 Planning Organic Syntheses (SB p.122) The organic compounds that are now known: • Only small fractions of them can be isolated from natural resources • All the remaining are synthesized by organic chemists • Reasons for carrying out syntheses: • e.g. To make a new medicine, dye, plastics, pesticide; • To make a new compound for studying reaction mechanisms or metabolic pathways

3. 37.1 Planning Organic Syntheses (SB p.122) • The way to plan the synthesis is to think backwards  From the desired product to simpler molecules that can act as the precursor for our target molecule • A synthesis usually involves more than one step

4. 37.1 Planning Organic Syntheses (SB p.123) There are usually more than one way to carry out a synthesis

5. 37.1 Planning Organic Syntheses (SB p.123) The feasibility of an organic synthesis depends on a number of factors: • Numbers of steps involved in the synthesis • Availability of starting materials and reagents • Duration of the synthetic process

6. 37.1 Planning Organic Syntheses (SB p.123) Numbers of Steps involved in the Synthesis • Most organic reactions are reversible and seldom proceed to completion • As the backward reaction takes place, it is impossible to have a 100% yield of product from each step of the synthetic route

7. 37.1 Planning Organic Syntheses (SB p.123) e.g. • The yield of desired product is 12.96% • ∴ an efficient route of synthesis consists of a minimal number of steps • Usually the number of steps is limited to not more than four

8. 37.1 Planning Organic Syntheses (SB p.123) Availability of Starting Materials and Reagents • There are often a restricted number of simple, relatively cheap organic compounds available • e.g. simple haloalkanes, alcohols of not more than four carbon atoms, simple aromatic compounds such as benzene and methylbenzene

9. 37.1 Planning Organic Syntheses (SB p.124) Duration of the Synthetic Process • The time factor must be considered when planning the synthetic pathway • ∵ many organic reactions proceed at a relatively slow ratee.g. acid-catalyzed esterification requires the reaction mixture to be refluxed for a whole day • Involvement of slow reactions in the synthetic route is impractical as the reaction will be too long

10. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.124) Oxidation • Oxidation of an organic compound usually corresponds to increasing its oxygen content or decreasing its hydrogen content • Common oxidizing agents used: KMnO4, K2Cr2O7 or H2CrO4 • KMnO4 is the strongest oxidizing agent and can be used in acidic, neutral or alkaline medium • Other oxidizing agents: Tollens’ reagent, Fehling’s reagent, ozone

11. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.125) Potassium Manganate(VII) 1. Mild Oxidation by Potassium Manganate(VII) Under mild oxidation by alkaline KMnO4, alkenes are oxidized to diols

12. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.125) 2. Vigorous Oxidation by Potassium Manganate(VII) • Occur in acidic or alkaline medium • Heating is to ensure the vigour of the reaction

13. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.125) • Alkylbenzenes are converted to benzoic acid by vigorous oxidation of KMnO4

14. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.126) • 1° alcohols are oxidized to carboxylic acids by vigorous oxidation of KMnO4 • The oxidation is difficult to stop at the aldehyde stage. • The way to obtain aldehyde from oxidation is to remove the aldehyde by distillation as soon as they formed

15. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.126) Potassium Dichromate(VI) or Sodium Dichromate(VI) • The most commonly used chromium(VI) reagent is H2CrO4 which is prepared by adding CrO3, Na2Cr2O7 or K2Cr2O7 to aqueous H2SO4 • It oxidizes 1° alcohols or aromatic side chains to aldehydes but not in good yields

16. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.126) • It is most often used to oxidize 2° alcohols to ketones in excellent yields

17. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.126) Tollens’ and Fehling’s Reagents • Tollens’ and Fehling’s reagents are weak oxidizing agents which are able to oxidize aldehydes to carboxylate ions

18. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.126) Ozone • Ozonolysis is the most important oxidation reaction of alkenes • This reaction provides a method for locating the double bond of an alkene • Ozone reacts vigorously with alkenes to form ozonides and then reduced by treatment with Zn and H2O to give carbonyl compounds

19. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.127) (a) (b) Check Point 37-1 Show how each of the following transformations could be accomplished. (a) (b) Answer

20. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.127) (c) (d) Check Point 37-1 Show how each of the following transformations could be accomplished. (c) (d) Answer

21. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.128) Reduction Reduction of an organic compound usually corresponds to increasing its hydrogen content or decreasing its oxygen content Examples:

22. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.128) Hydrogen with Transition Metal Catalyst • Hydrogen is added to the C = C and C  C bonds in alkenes and alkynes in the presence of transition metal catalysts

23. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.129) • Nitriles or nitro compoundsare reduced to amines by hydrogen in the presence of transition metal catalysts

24. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.129) Lithium Tetrahydridoaluminate • LiAlH4 is a powerful reducing agent • It reduces carboxylic acids, esters, aldehydes, ketones, amides, nitriles and nitro compounds

25. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.129)

26. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.129) • LiAlH4cannot normally reduce unsaturated centres like C = C and C  C bonds and benzene ring • Reduction with LiAlH4 must be carried out in anhydrous solutions∵ LiAlH4 reacts violently with water

27. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.130) Sodium Tetrahydridoborate • NaBH4 is a less powerful reducing agent than LiAlH4 • It reduces aldehydes and ketones only • It can be used in water or alcohols

28. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.130) (a) LiAlH4 (b) LiAlH4 (c) NaBH4 Check Point 37-2 Which reducing agent, LiAlH4 or NaBH4, would you use to carry out the following transformations? (a) (b) (c) Answer

29. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.130) Zinc, Tin, Tin(II) Chloride or Iron with Hydrochloric acid Aromatic nitro group can be reduced to amines by treatment with HCl and Fe, Zn or Sn, or a metal salt such as SnCl2

30. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.131) Substitution • Free radical substitution of alkanes with halogens forms haloalkanes • A mixture of mono-, di- and poly-substituted haloalkanes is formed • RH + X2 RX + HX

31. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.131) • Various aromatic compounds can be prepared from benzene by electrophilic substitution of a hydrogen atom by substituents

32. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.131) • Haloalkanes can be converted into alcohols, nitriles or amines by substitution reactions R – X + OH– R – OH + X–

33. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.131) (X = Cl or Br) Addition • Addition of alkenes and alkynes with various reagents can produce haloalkanes, haloalcohols, alcohols, alkanes and polymers

34. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.132)

35. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.132) • Carbonyl compounds undergo addition reaction with hydrogen cyanide for form hydroxyalkanenitriles • Addition of hydrogen to nitriles yields amines

36. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.132) Elimination • Haloalkanes can be converted to alkenes by elimination with alcoholic KOH or NaOH • Dihaloalkanes (with one halogen atom on each of two adjacent carbon atoms) can be converted to alkynes by elimination

37. 37.2 Interconversions of Functional Groups of Organic Compounds (SB p.132) • Alcohols undergo dehydration to give alkenes by treatment with conc. H2SO4

38. 37.2 Chain Lengthening or Shortening of Carbon Skeleton (SB p.133) Methods of Chain Lengthening • The carbon chain is lengthened by one when haloalkanes react with NaCN to form nitriles • Hydrolysis of nitriles gives carboxylic acids, while hydrogenation of nitriles gives 1° amines

39. 37.2 Chain Lengthening or Shortening of Carbon Skeleton (SB p.133) • The carbon chain is also lengthened by one when carbonyl compounds react with HCN to form 2-hydroxyalkanenitriles • Hydrolysis of the 2-hydroxyalkanenitriles yields 2-hydroxycarboxylic acids

40. 37.2 Chain Lengthening or Shortening of Carbon Skeleton (SB p.133) Methods of Chain Shortening • In Hofmann degradation of amides, the carbon chain is reduced by one carbon atom

41. 37.2 Chain Lengthening or Shortening of Carbon Skeleton (SB p.134) In the triiodomethane formation reaction (iodoform reaction) of alcohols containing the group and aldehydes or ketones containing the group, the carbon chain is also degraded by one carbon atom

42. 37.2 Chain Lengthening or Shortening of Carbon Skeleton (SB p.134)

43. 37.2 Chain Lengthening or Shortening of Carbon Skeleton (SB p.134) • In ozonolysis, alkenes react with ozone to from ozonide which is reduced by using Zn and H2O to produce a mixture of carbonyl compounds resulting from the cleavage of the C = C bond • The cleavage of the C = C bond results in the degradation of carbon chain

44. 37.3 Chain Lengthening or Shortening of Carbon Skeleton (SB p.133) (a) Check Point 37-3 By means of simple chemical equations, indicate how you would carry out the following conversion, which may involve more than one step. Give the reagents for each step and indicate the major product formed. (a) Answer

45. 37.3 Chain Lengthening or Shortening of Carbon Skeleton (SB p.133) (b) Check Point 37-3 By means of simple chemical equations, indicate how you would carry out the following conversion, which may involve more than one step. Give the reagents for each step and indicate the major product formed. (b) Answer

46. 37.3 Chain Lengthening or Shortening of Carbon Skeleton (SB p.133) (c) Check Point 37-3 By means of simple chemical equations, indicate how you would carry out the following conversion, which may involve more than one step. Give the reagents for each step and indicate the major product formed. (c) Answer

47. 37.3 Chain Lengthening or Shortening of Carbon Skeleton (SB p.133) (d) Check Point 37-3 By means of simple chemical equations, indicate how you would carry out the following conversion, which may involve more than one step. Give the reagents for each step and indicate the major product formed. (d) Answer

48. The END