1. 22.16 Nitrosation of Alkylamines

2. Nitrite Ion, Nitrous Acid, and Nitrosyl Cation H+ –O NO O NO H H+ O NO HH + + NO + O HH

3. Nitrosyl Cation and Nitrosation + NO

4. Nitrosyl Cation and Nitrosation + NO + N N NO +

5. Nitrosation of Secondary Alkylamines + NO + N NO + N H H + H + N NO nitrosation of secondary amines gives an N-nitroso amine

6. Example (CH 3 ) 2 NH NaNO 2, HCl H2OH2OH2OH2O (88-90%) (CH 3 ) 2 N NO

7. Some N-Nitroso Amines N-nitrosopyrrolidine (nitrite-cured bacon) N-nitrosonornicotine (tobacco smoke) N N O N N O N (CH 3 ) 2 N NO N-nitrosodimethylamine (leather tanning)

8. Nitrosation of Primary Alkylamines + N NO + H + H + N NO analogous to nitrosation of secondary amines to this point + NO N H HRH R R H

9. Nitrosation of Primary Alkylamines N NO this species reacts further R H

10. Nitrosation of Primary Alkylamines N NO R H H+ N NO RH H +

11. Nitrosation of Primary Alkylamines N NO RH H + N NO RH H+

12. Nitrosation of Primary Alkylamines + N NO RH H H+ N NO R H

13. Nitrosation of Primary Alkylamines + H N NO RH

14. Nitrosation of Primary Alkylamines + H N NO RH +N N R H O H + nitrosation of a primary alkylamine gives an alkyl diazonium ion process is called diazotization

15. Alkyl Diazonium Ions +N N R alkyl diazonium ions readily lose N 2 to give carbocations R++NN

16. Example: Nitrosation of 1,1-Dimethylpropylamine H2OH2OH2OH2O NH 2 OH + N N+ HONO+ (80%) (2%)(3%) – N 2 Fig. 22.5 (p 890)

17. There is no useful chemistry associated with the nitrosation of tertiary alkylamines. Nitrosation of Tertiary Alkylamines N RRR N NO + RRR

18. 22.17 Nitrosation of Arylamines

19. reaction that occurs is electrophilic aromatic substitution Nitrosation of Tertiary Arylamines (95%) N(CH 2 CH 3 ) 2 1. NaNO 2, HCl, H 2 O, 8°C 2. HO – N(CH 2 CH 3 ) 2 N O

20. similar to secondary alkylamines; gives N-nitroso amines Nitrosation of N-Alkylarylamines (87-93%) NaNO 2, HCl, H 2 O, 10°C NHCH 3 NCH 3 NO

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

22. Nitrosation of Primary Arylamines gives aryl diazonium ions aryl diazonium ions are much more stable than alkyl diazonium ions most aryl diazonium ions are stable under the conditions of their formation (0-10°C) ArN N+ RNN+fast slow R++ N2N2N2N2 Ar + + N2N2N2N2

23. Example: (CH 3 ) 2 CH NH 2 NaNO 2, H 2 SO 4 H 2 O, 0-5°C (CH 3 ) 2 CH N N + HSO 4 –

24. Synthetic Origin of Aryl Diazonium Salts ArH Ar NO2NO2NO2NO2 Ar NH2NH2NH2NH2 Ar N N+

25. 22.18 Synthetic Transformations of Aryl Diazonium Salts

26. Transformations of Aryl Diazonium Salts Ar N N+ ArH ArOH ArI ArF ArBrArCl ArCN

27. Preparation of Phenols Ar N N+ ArOH H 2 O, heat hydrolysis of a diazonium salt

28. Example 2. H 2 O, heat (CH 3 ) 2 CH NH2NH2NH2NH2 1. NaNO 2, H 2 SO 4 H 2 O, 0-5°C H 2 O, 0-5°C (CH 3 ) 2 CH OHOHOHOH (73%)

29. Transformations of Aryl Diazonium Salts Ar N N+ ArH ArOH ArI ArF ArBrArCl ArCN

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

31. Example 2. KI, room temp. 1. NaNO 2, HCl H 2 O, 0-5°C H 2 O, 0-5°C (72-83%) NH2NH2NH2NH2Br I Br

32. Transformations of Aryl Diazonium Salts Ar N N+ ArH ArOH ArI ArF ArBrArCl ArCN

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

34. Example (68%) NH2NH2NH2NH2 CCH 2 CH 3 O 2. HBF 4 1. NaNO 2, HCl, H 2 O, 0-5°C H 2 O, 0-5°C 3. heat F CCH 2 CH 3 O

35. Transformations of Aryl Diazonium Salts Ar N N+ ArH ArOH ArI ArF ArBrArCl ArCN

36. Preparation of Aryl Chlorides and Bromides Ar N N+ ArBrArCl 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 Sandmeyer reactions

37. Example (68-71%) NH2NH2NH2NH2 NO 2 2. CuCl, heat 1. NaNO 2, HCl, H 2 O, 0-5°C H 2 O, 0-5°C Cl NO 2

38. Example (89-95%) 2. CuBr, heat 1. NaNO 2, HBr, H 2 O, 0-10°C H 2 O, 0-10°C NH2NH2NH2NH2Cl Br Cl

39. Transformations of Aryl Diazonium Salts Ar N N+ ArH ArOH ArI ArF ArBrArCl ArCN

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

41. Example (64-70%) 2. CuCN, heat 1. NaNO 2, HCl, H 2 O, 0°C H 2 O, 0°C NH2NH2NH2NH2 CH 3 CN

42. Transformations of Aryl Diazonium Salts Ar N N+ ArH ArOH ArI ArF ArBrArCl ArCN

43. Ar N N+ ArH hypophosphorous acid (H 3 PO 2 ) reduces diazonium salts; ethanol does the same thing this is called reductive deamination

44. Example (70-75%) NaNO 2, H 2 SO 4, H 3 PO 2 H 3 PO 2 NH2NH2NH2NH2 CH 3

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. NH2NH2NH2NH2Br Br Br Example (74-77%) NaNO 2, H 2 SO 4, H 2 O, CH 3 CH 2 OH NH2NH2NH2NH2 Br 2 H2OH2OH2OH2O (100%) BrBrBr

47. 22.19 Azo Coupling

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

49. Azo Coupling Diazonium salts are weak electrophiles. React with strongly activated aromatic compounds by electrophilic aromatic substitution. Ar N N+ Ar'H+ ArNN Ar' an azo compound Ar' must bear a strongly electron-releasing group such as OH, OR, or NR 2.

50. ExampleOH+ C6H5NC6H5NC6H5NC6H5N N+ OHN NC 6 H 5 Cl –