1. Dr. Wolf's CHM 201 & 202 22-1 22.15 Nitrosation of Alkylamines

2. Dr. Wolf's CHM 201 & 202 22-2 Nitrite Ion, Nitrous Acid, and Nitrosyl Cation H+ –O NO O NO H H+O NO H H + + NO + O HH

3. Dr. Wolf's CHM 201 & 202 22-3 Nitrosyl Cation and Nitrosation + NO

4. Dr. Wolf's CHM 201 & 202 22-4 Nitrosyl Cation and Nitrosation + NO + N N NO +

5. Dr. Wolf's CHM 201 & 202 22-5 Nitrosation of Secondary Alkylamines + NO N H + N NO + H + H + N NO nitrosation of secondary amines gives an N-nitroso amine

6. Dr. Wolf's CHM 201 & 202 22-6 Example (CH 3 ) 2 NH NaNO 2, HCl H2OH2OH2OH2O (88-90%) (CH 3 ) 2 N NO

7. Dr. Wolf's CHM 201 & 202 22-7 Some N-Nitroso Amines N-nitrosopyrrolidine (nitrite-cured bacon) N N O N-nitrosonornicotine (tobacco smoke) N N O N (CH 3 ) 2 N NO N-nitrosodimethylamine (leather tanning)

8. Dr. Wolf's CHM 201 & 202 22-8 Nitrosation of Primary Alkylamines + analogous to nitrosation of secondary amines to this point + NO N H HR N NO + H HR+ H + N NO R H

9. Dr. Wolf's CHM 201 & 202 22-9 Nitrosation of Primary Alkylamines N NO R H H + N NO RH H + this species reacts further N NO R H H + + H H + N NO RH

10. Dr. Wolf's CHM 201 & 202 22-10 Nitrosation of Primary Alkylamines + H N NO RH + N N RH O H + nitrosation of a primary alkylamine gives an alkyl diazonium ion process is called diazotization

11. Dr. Wolf's CHM 201 & 202 22-11 Alkyl Diazonium Ions +N N R alkyl diazonium ions readily lose N 2 to give carbocations R++NN

12. Dr. Wolf's CHM 201 & 202 22-12 Example: Nitrosation of 1,1-Dimethylpropylamine NH2NH2NH2NH2 N N+ HONO H2OH2OH2OH2O OHOHOHOH (80%) + (2%)(3%) + – N 2

13. Dr. Wolf's CHM 201 & 202 22-13 There is no useful chemistry associated with the nitrosation of tertiary alkylamines. Nitrosation of Tertiary Alkylamines N RRR N NO + RRR

14. Dr. Wolf's CHM 201 & 202 22-14 22.16 Nitrosation of Arylamines

15. Dr. Wolf's CHM 201 & 202 22-15 reaction that occurs is electrophilic aromatic substitution Nitrosation of Tertiary Arylamines N(CH 2 CH 3 ) 2 (95%) 1. NaNO 2, HCl, H 2 O, 8°C 2. HO – N(CH 2 CH 3 ) 2 N O

16. Dr. Wolf's CHM 201 & 202 22-16 similar to secondary alkylamines; gives N-nitroso amines Nitrosation of N-Alkylarylamines NaNO 2, HCl, H 2 O, 10°C NHCH 3 (87-93%) NCH 3 NO

17. Dr. Wolf's CHM 201 & 202 22-17 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 + RNRNRNRNN+fast slow R + + N2N2N2N2 Ar + + N2N2N2N2

18. Dr. Wolf's CHM 201 & 202 22-18 Example: (CH 3 ) 2 CH NH2NH2NH2NH2 NaNO 2, H 2 SO 4 H 2 O, 0-5°C (CH 3 ) 2 CH N N + HSO 4 –

19. Dr. Wolf's CHM 201 & 202 22-19 Synthetic Origin of Aryl Diazonium Salts ArH Ar NO2NO2NO2NO2 Ar NH2NH2NH2NH2 Ar N N+

20. Dr. Wolf's CHM 201 & 202 22-20 22.17 Synthetic Transformations ofAryl Diazonium Salts

21. Dr. Wolf's CHM 201 & 202 22-21 Transformations of Aryl Diazonium Salts Ar N N+ ArH Ar OHOHOHOH ArI ArF ArBrArCl ArCN

22. Dr. Wolf's CHM 201 & 202 22-22 Preparation of Phenols Ar N N+ Ar OHOHOHOH H 2 O, heat

23. Dr. Wolf's CHM 201 & 202 22-23 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%)

24. Dr. Wolf's CHM 201 & 202 22-24 Transformations of Aryl Diazonium Salts Ar N N+ ArH Ar OHOHOHOH ArI ArF ArBrArCl ArCN

25. Dr. Wolf's CHM 201 & 202 22-25 Preparation of Aryl Iodides Ar N N+ ArI reaction of an aryl diazonium salt with potassium iodide KIKIKIKI

26. Dr. Wolf's CHM 201 & 202 22-26 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

27. Dr. Wolf's CHM 201 & 202 22-27 Transformations of Aryl Diazonium Salts Ar N N+ ArH Ar OHOHOHOH ArI ArF ArBrArCl ArCN

28. Dr. Wolf's CHM 201 & 202 22-28 Preparation of Aryl Fluorides Ar N N+ ArF heat the tetrafluoroborate salt of a diazonium ion; process is called the Schiemann reaction

29. Dr. Wolf's CHM 201 & 202 22-29 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

30. Dr. Wolf's CHM 201 & 202 22-30 Transformations of Aryl Diazonium Salts Ar N N+ ArH Ar OHOHOHOH ArI ArF ArBrArCl ArCN

31. Dr. Wolf's CHM 201 & 202 22-31 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

32. Dr. Wolf's CHM 201 & 202 22-32 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

33. Dr. Wolf's CHM 201 & 202 22-33 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

34. Dr. Wolf's CHM 201 & 202 22-34 Transformations of Aryl Diazonium Salts Ar N N+ ArH Ar OHOHOHOH ArI ArF ArBrArCl ArCN

35. Dr. Wolf's CHM 201 & 202 22-35 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

36. Dr. Wolf's CHM 201 & 202 22-36 Example (64-70%) 2. CuCN, heat 1. NaNO 2, HCl, H 2 O, 0°C H 2 O, 0°C NH2NH2NH2NH2 CH 3 CN

37. Dr. Wolf's CHM 201 & 202 22-37 Transformations of Aryl Diazonium Salts Ar N N+ ArH Ar OHOHOHOH ArI ArF ArBrArCl ArCN

38. Dr. Wolf's CHM 201 & 202 22-38 Transformations of Aryl Diazonium Salts Ar N N+ ArH hypophosphorous acid (H 3 PO 2 ) reduces diazonium salts; ethanol does the same thing this is called reductive deamination

39. Dr. Wolf's CHM 201 & 202 22-39 Example (70-75%) NaNO 2, H 2 SO 4, H 3 PO 2 H 3 PO 2 NH2NH2NH2NH2 CH 3

40. Dr. Wolf's CHM 201 & 202 22-40 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

41. Dr. Wolf's CHM 201 & 202 22-41 Example BrBrBr NH2NH2NH2NH2Br Br Br (74-77%) NaNO 2, H 2 SO 4, H 2 O, CH 3 CH 2 OH NH2NH2NH2NH2 Br 2 H2OH2OH2OH2O (100%)

42. Dr. Wolf's CHM 201 & 202 22-42 22.18 Azo Coupling

43. Dr. Wolf's CHM 201 & 202 22-43 Azo Coupling Diazonium salts are weak electrophiles. React with strongly activated aromatic compounds by electrophilic aromatic substitution. Ar N N+Ar' H + Ar N N Ar' an azo compound Ar' must bear a strongly electron-releasing group such as OH, OR, or NR 2.

44. Dr. Wolf's CHM 201 & 202 22-44 ExampleOH+ C6H5NC6H5NC6H5NC6H5N N+ OHN NC 6 H 5 Cl –

45. Dr. Wolf's CHM 201 & 202 22-45 Section 22.19 Spectroscopic Analysis of Amines

46. Dr. Wolf's CHM 201 & 202 22-46 the N—H stretching band appears in the range 3000-3500 cm -1 primary amines give two peaks in this region, one for a symmetrical stretching vibration, the other for an antisymmetrical stretch Infrared Spectroscopy R NHH symmetric R NHH antisymmetric

47. Dr. Wolf's CHM 201 & 202 22-47 Infrared Spectroscopy RNH 2 R 2 NH primary amines give two N—H stretching peaks, secondary amines give one

48. Dr. Wolf's CHM 201 & 202 22-48 compare chemical shifts in: 1 H NMR H3CH3CH3CH3C CH 2 NH 2 H3CH3CH3CH3C CH 2 OH N C H is more shielded than  3.9 ppm  4.7 ppm O C H

49. Dr. Wolf's CHM 201 & 202 22-49 13 C NMR Carbons bonded to N are more shielded than those bonded to O. CH 3 NH 2 CH 3 OH  26.9 ppm  48.0 ppm

50. Dr. Wolf's CHM 201 & 202 22-50 max 204 nm 256 nm max 204 nm 256 nm max 230 nm 280 nm max 230 nm 280 nm max 203 nm 254 nm max 203 nm 254 nm An amino group on a benzene ring shifts max to longer wavelength. Protonation of N causes UV spectrum to resemble that of benzene. UV-VIS NH 2 NH 3 +

51. Dr. Wolf's CHM 201 & 202 22-51 Mass Spectrometry Compounds that contain only C, H, and O have even molecular weights. If an odd number of N atoms is present, the molecular weight is odd. A molecular-ion peak with an odd m/z value suggests that the sample being analyzed contains N.

52. Dr. Wolf's CHM 201 & 202 22-52 Mass Spectrometry Nitrogen stabilizes carbocations, which drives the fragmentation pathways. (CH 3 ) 2 NCH 2 CH 2 CH 2 CH 3 e–e–e–e– + CH 2 CH 2 CH 3 CH 2 CH 2 CH 3 + (CH 3 ) 2 N CH 2 +

53. Dr. Wolf's CHM 201 & 202 22-53 Mass Spectrometry Nitrogen stabilizes carbocations, which drives the fragmentation pathways. CH 3 NHCH 2 CH 2 CH(CH 3 ) 2 e–e–e–e– + CH 2 CH(CH 3 ) 2 CH 2 CH(CH 3 ) 2 + CH 3 NH CH 2 +

54. Dr. Wolf's CHM 201 & 202 22-54 End of Chapter 22