22.16 Nitrosation of Alkylamines

1. 22.16Nitrosation of Alkylamines

2. + H – •• •• •• •• •• •• O O N O N O H •• •• •• •• •• + H H H + •• •• •• •• O N O O N O •• •• •• •• •• + H H Nitrite Ion, Nitrous Acid, and Nitrosyl Cation +

3. •• •• N O •• + Nitrosyl Cation and Nitrosation

4. + •• •• N N O •• •• •• N N O •• •• + Nitrosyl Cation and Nitrosation +

5. + •• •• •• •• N N N O N O •• •• •• •• •• N N O •• •• + H Nitrosation of Secondary Alkylamines • nitrosation of secondary amines gives an N-nitroso amine + H + H +

6. •• •• •• N O (CH3)2NH (CH3)2N •• Example NaNO2, HCl •• H2O (88-90%)

7. N O (CH3)2N N N N N N O O Some N-Nitroso Amines N-nitrosodimethylamine(leather tanning) N-nitrosopyrrolidine(nitrite-cured bacon) N-nitrosonornicotine(tobacco smoke)

8. + •• •• •• •• N N N O N O •• •• •• R H •• •• N N O •• •• + H Nitrosation of Primary Alkylamines R R H • analogous to nitrosation of secondary amines to this point + H H + H +

9. •• •• N N O •• •• Nitrosation of Primary Alkylamines R • this species reacts further H

10. R + H •• •• •• •• + N N N O N O •• •• •• H H Nitrosation of Primary Alkylamines R H

11. R •• •• + N N O •• H H R •• •• N N O •• •• H + H Nitrosation of Primary Alkylamines

12. R H + H •• •• N N O •• •• H Nitrosation of Primary Alkylamines R •• N N O •• •• + H

13. R H •• N N O •• •• + H Nitrosation of Primary Alkylamines

14. H + O N N R •• •• •• H R H •• N N O •• •• + H Nitrosation of Primary Alkylamines • nitrosation of a primary alkylamine gives an alkyl diazonium ion • process is called diazotization +

15. + + N N N R R N •• •• •• Alkyl Diazonium Ions • alkyl diazonium ions readily lose N2 to give carbocations +

16. + HONO N N NH2 OH + Example: Nitrosation of 1,1-Dimethylpropylamine – N2 H2O (80%) + (3%) (2%) Fig. 22.5 (p 890)

17. R R R R + •• •• N N N O •• •• R R Nitrosation of Tertiary Alkylamines • There is no useful chemistry associated with the nitrosation of tertiary alkylamines.

18. 22.17Nitrosation of Arylamines

19. N(CH2CH3)2 N(CH2CH3)2 N O Nitrosation of Tertiary Arylamines • reaction that occurs is electrophilic aromatic substitution 1. NaNO2, HCl, H2O, 8°C 2. HO– (95%)

20. N O NHCH3 NCH3 Nitrosation of N-Alkylarylamines • similar to secondary alkylamines; • gives N-nitroso amines NaNO2, HCl,H2O, 10°C (87-93%)

21. Nitrosation of Primary Arylamines • gives aryl diazonium ions • aryl diazonium ions are much more stable thanalkyl diazonium ions • most aryl diazonium ions are stable under the conditions of their formation (0-10°C)

22. + + + R N2 RN N + N ArN Nitrosation of Primary Arylamines • gives aryl diazonium ions • aryl diazonium ions are much more stable thanalkyl diazonium ions • most aryl diazonium ions are stable under the conditions of their formation (0-10°C) fast slow + + Ar N2

23. NH2 (CH3)2CH NaNO2, H2SO4 H2O, 0-5°C + N (CH3)2CH N Example: HSO4–

24. H Ar NO2 Ar NH2 Ar + N N Ar Synthetic Origin of Aryl Diazonium Salts

25. 22.18Synthetic Transformations of Aryl Diazonium Salts

26. Cl Br Ar Ar F Ar CN Ar + N N Ar H I Ar Ar OH Ar Transformations of Aryl Diazonium Salts

27. + N N Ar OH Ar Preparation of Phenols • hydrolysis of a diazonium salt H2O, heat

28. NH2 (CH3)2CH OH (CH3)2CH Example 1. NaNO2, H2SO4 H2O, 0-5°C 2. H2O, heat (73%)

29. Cl Br Ar Ar F Ar CN Ar + N N Ar H I Ar Ar OH Ar Transformations of Aryl Diazonium Salts

30. + N N Ar I Ar Preparation of Aryl Iodides • reaction of an aryl diazonium salt with potassium iodide KI

31. NH2 Br Example I 1. NaNO2, HCl H2O, 0-5°C Br 2. KI, room temp. (72-83%)

32. Cl Br Ar Ar F Ar CN Ar + N N Ar H I Ar Ar OH Ar Transformations of Aryl Diazonium Salts

33. F Ar + N N Ar Preparation of Aryl Fluorides • heat the tetrafluoroborate salt of a diazonium ion; • process is called the Schiemann reaction

34. NH2 F CCH2CH3 CCH2CH3 O O Example 1. NaNO2, HCl, H2O, 0-5°C 2. HBF4 3. heat (68%)

35. Cl Br Ar Ar F Ar CN Ar + N N Ar H I Ar Ar OH Ar Transformations of Aryl Diazonium Salts

36. Cl Br Ar Ar + N N Ar Preparation of Aryl Chlorides and Bromides • aryl chlorides and aryl bromides are prepared by heating a diazonium salt with copper(I) chloride or bromide • substitutions of diazonium salts that use copper(I) halides are called Sandmeyerreactions

37. Example NH2 Cl 1. NaNO2, HCl, H2O, 0-5°C 2. CuCl, heat NO2 NO2 (68-71%)

38. NH2 Cl Example 1. NaNO2, HBr, H2O, 0-10°C Br Cl 2. CuBr, heat (89-95%)

39. Cl Br Ar Ar F Ar CN Ar + N N Ar H I Ar Ar OH Ar Transformations of Aryl Diazonium Salts

40. CN Ar + N N Ar Preparation of Aryl Nitriles • aryl nitriles are prepared by heating a diazonium salt with copper(I) cyanide • this is another type of Sandmeyer reaction

41. NH2 CH3 Example 1. NaNO2, HCl, H2O, 0°C CN CH3 2. CuCN, heat (64-70%)

42. Cl Br Ar Ar F Ar CN Ar + N N Ar H I Ar Ar OH Ar Transformations of Aryl Diazonium Salts

43. + N N Ar H Ar Transformations of Aryl Diazonium Salts • hypophosphorous acid (H3PO2) reduces diazonium salts; ethanol does the same thing • this is called reductive deamination

44. NH2 CH3 CH3 Example NaNO2, H2SO4, H3PO2 (70-75%)

45. Value of Diazonium Salts • 1) allows introduction of substituents such as OH, F, I, and CN on the ring • 2) allows preparation of otherwise difficultly accessible substitution patterns

46. NH2 NH2 Br Br Br2 H2O Br Br Br Br Example NaNO2, H2SO4,H2O, CH3CH2OH (100%) (74-77%)

47. 22.19Azo Coupling

48. Azo Coupling • Diazonium salts are weak electrophiles. • React with strongly activated aromatic compounds by electrophilic aromatic substitution.

49. + H N N N N Ar' Ar Ar Ar' Azo Coupling • Diazonium salts are weak electrophiles. • React with strongly activated aromatic compounds by electrophilic aromatic substitution. + an azo compound Ar' must bear a strongly electron-releasing group such as OH, OR, or NR2.

50. OH + N C6H5N OH N NC6H5 Example + Cl–