ORGANIC REACTIONS

1. CHEM 353 BRIEF REVIEW OF ORGANIC REACTIONS METHODS OF SYNTHESIS FOR THE MAJOR FUNCTIONAL GROUPS OF ORGANIC CHEM

2. THIS SET OF SLIDES IS STILL UNDER CONSTRUCTION. PLEASE BE PATIENT

3. ACID HALIDES

4. SYNTHESIS OF ACID CHLORIDES thionyl chloride + SO2 + HCl Thionyl chloride is a liquid. You can do the reaction without a solvent or sometimes benzene is used. All of the other acid derivatives can be made from the acid chloride.

5. ALCOHOLS

6. SYNTHESIS OF ALCOHOLS H2 Ni catalytic hydrogenation 2 atm 40o ketone or aldehyde low reactivity water and alcohol solvents are OK 1. NaBH4 sodium borohydride 2. H3O+ reduces only aldehydes or ketones lithium aluminum hydride 1. LiAlH4 ether solvent required 2. H3O+ reduces aldehydes and ketones and many other polar functional groups CAUTION:

7. SYNTHESIS OF ALCOHOLS - 2 gives low yields, hydration of an alkene oxymercuration is a better method H2SO4 Markovnikov rule oxymer- curation 1. 2. Markovnikov

8. SYNTHESIS OF ALCOHOLS - 3 H2O solvolysis of halides tertiary, allylic or benzylic Grignard Reaction H3O+ + Mg ether alkyllithium compounds react just like the Grignard Li Alkyllithium Compounds ether or pentane or benzene solvent

9. SYNTHESIS OF ALCOHOLS - 4 ether hydroboration- oxidation 3 H2O2 NaOH H3O+ 3 anti-Markovnikoff Grignard + epoxide 1. RMgX / ether 2. H3O+ SN2 terminal alcohols

10. Grignard + oxetane

11. ALDEHYDES

12. SYNTHESIS OF ALDEHYDES Sarrett Reagent primary alcohol Jones Reagent does not stop at the aldehyde and gives a carboxylic acid. Other oxidizing agents usually continue to the acid RCOOH.

13. Mild Cleavage of alkenes

14. ALKENES

15. SYNTHESIS OF ALKENES E2 elimination heat NaOMe stereospecific anti MeOH X = Cl, Br, I Saytzev Rule strong bases such as NaOH, NaOR required dehydration watch for rearrangements H2SO4 not stereospecific heat acid-assisted E1 elimination Saytzev Rule strong acids such as H2SO4 and H3PO4 required

16. SYNTHESIS OF ALKENES - 2 catalytic hydrogenation H2 Lindlar cis Lindlar = Pd / BaSO4 / quinoline syn addition H2 won’t stop Pd REMEMBER 2X dissolving metal reduction Na/NH3 trans anti addition

17. SYNTHESIS OF ALKENES - 3 Wittig reaction R R 1 benzene 2 + _ : + (C H ) P ( C H ) P C R X R C X 6 5 3 6 5 3 2 1 heat H H - .. Triphenylphosphine : O-CH3 halide .. ether strong base R - + .. 1 ( C H ) P C 6 5 3 R ylide 2 Wittig reagent reaction assembles the two halves

18. ALKYNES

19. C a C O C a O + C O 3 2 C a O + 2 C C a C + C O 2 C a ( O H ) C a C H O + + 2 2 2 2 H C C H SYNTHESIS OF ACETYLENES Acetylene from limestone D calcium oxide calcium carbonate D calcium carbide lime acetylene

20. SYNTHESIS OF ACETYLENES - 2 alkylation of acetylene elimination of dihalides

21. AMIDES

22. acid chloride or anhydride with ammonia

23. AMINES

24. ANHYDRIDES

25. SYNTHESIS OF ANHYDRIDES acid chloride and sodium salt - + sodium salt Section 19.25 acid chloride anhydride + NaCl

26. SYNTHESIS OF ANHYDRIDES - 2 dehydration of carboxylic acids works for small symmetric anhydrides only

27. acids + sulfuric acid

28. CARBOXYLIC ACIDS

29. SYNTHESIS OF CARBOXYLIC ACIDS Jones Reagent cannot isolate primary alcohol oxidation continues Sarrett Reagent will stop at the aldehyde. carboxylic acid oxidation of an aldehyde [Ox] Many oxidizing agents will oxidize aldehydes including: CrO3, K2Cr2O7, KMnO4, H2O2, Ag(NH4)OH (Tollen’s).

30. SYNTHESIS OF CARBOXYLIC ACIDS - 2 Grignard or R-Li + CO2 1) CO2 R-MgX R-COOH 2) H3O+ 1) CO2 R-COOH R-Li 2) H3O+ cleaving double and triple bonds (oxidation) KMnO4 KMnO4 cannot isolate oxidation continues Alkenes must have hydrogen on the double bond. …..

31. SYNTHESIS OF CARBOXYLIC ACIDS - 3 D hydrolysis of a nitrile NaCN H2O R-X R-CN R-COOH H2SO4 acetone NaOH D H2O H3O+ - + R-COO Na hydrolysis of acid derivatives H2O or or H2O H2SO4 or NaOH

32. SYNTHESIS OF CARBOXYLIC ACIDS - 4 oxidation of a side chain on an aromatic ring KMnO4 or CrO3/H2SO4

33. EPOXIDES

34. SYNTHESIS OF EPOXIDES peracid cis cis stereospecific via bromohydrin cis anti addition stereospecific overall cis

35. ESTERS

36. Fischer synthesis acid chloide or anhydride + alcohol

37. GLYCOLS DIOLS

38. HALIDES

39. SYNTHESIS OF HALIDES * # thionyl chloride pyridine inversion of configuration SN2 * * + + thionyl chloride ether retention of configuration SNi phosphorous halides 1o, 2o alcohols inversion of configuration SN2

40. SYNTHESIS OF HALIDES - 2 watch for rearrangements ! concentrated acids the halide is often racemized 1o, 2o alcohols proceed by SN2 3o, allylic, benzylic alcohols by SN1 (acid assisted)

41. SYNTHESIS OF HALIDES - 3 addition of HX to alkenes also HBr, HI Markovnikov rule free radical halogenation + hn rate = 3o H > 2o H > 1o H usually not a good laboratory synthetic method chain reaction

42. KETONES

43. oxidation of alcohols cleavage of alkenes

44. hydrolysis of imines don’t forget nitrile + Grignard don’t forget organocadmium + ester

45. NITRILES

46. NaCN is soluble in acetone, or DMSO could be used SN2 displacement with cyanide acetone + Primary or secondary halides cyanohydrins

47. RINGS

48. CYCLOHEXENES Diels-Alder CYCLOPROPANES Diazomethane a-Eliminations Simmons-Smith