1. Dr. Wolf's CHM 201 & 202 19-1 19.16  -Halogenation of Carboxylic Acids: The Hell-Volhard-Zelinsky Reaction

2. Dr. Wolf's CHM 201 & 202 19-2 analogous to  -halogenation of aldehydes and ketones key question: Is enol content of carboxylic acids high enough to permit reaction to occur at reasonable rate? (Answer is NO)  -Halogenation of Carboxylic Acids + X2X2X2X2 + HXHXHXHX R 2 CCOH OH OX

3. Dr. Wolf's CHM 201 & 202 19-3 reaction works well if a small amount of phosphorus or a phosphorus trihalide is added to the reaction mixture this combination is called the Hell-Volhard- Zelinsky reaction But... + X2X2X2X2 + HXHXHXHX R 2 CCOH OH OX P or PX 3

4. Dr. Wolf's CHM 201 & 202 19-4 Example CH 2 COH O PCl 3 benzene 80°C CHCOHOBr (60-62%) + Br 2

5. Dr. Wolf's CHM 201 & 202 19-5 Value CH 3 CH 2 CH 2 COH O Br 2 P CH 3 CH 2 CHCOH OBr (77%)  -Halogen can be replaced by nucleophilic substitution

6. Dr. Wolf's CHM 201 & 202 19-6 Value CH 3 CH 2 CH 2 COH O Br 2 P CH 3 CH 2 CHCOH OBr OOH (77%) (69%) K 2 CO 3 H 2 O heat

7. Dr. Wolf's CHM 201 & 202 19-7 Synthesis of  -Amino Acids (CH 3 ) 2 CHCH 2 COH O Br 2 PCl 3 (CH 3 ) 2 CHCHCOH OBr O NH 2 (88%) (48%) NH 3 H 2 O

8. Dr. Wolf's CHM 201 & 202 19-8 19.17 Decarboxylation of Malonic Acid and Related Compounds

9. Dr. Wolf's CHM 201 & 202 19-9 Decarboxylation of Carboxylic Acids Simple carboxylic acids do not decarboxylate readily. RH + CO 2 RCOHO

10. Dr. Wolf's CHM 201 & 202 19-10 Decarboxylation of Carboxylic Acids Simple carboxylic acids do not decarboxylate readily. But malonic acid does. RH + CO 2 RCOHO150°C CH 3 COH O+ CO 2 HOCCH 2 COH OO

11. Dr. Wolf's CHM 201 & 202 19-11 Mechanism of Decarboxylation One carboxyl group assists the loss of the other. OOOHHO HH OHO O O HH H

12. Dr. Wolf's CHM 201 & 202 19-12 Mechanism of Decarboxylation This compound is the enol form of acetic acid. OOOHHO HH H HOHHO OHO O O HH H + COO One carboxyl group assists the loss of the other.

13. Dr. Wolf's CHM 201 & 202 19-13 Mechanism of Decarboxylation OOOHHO HH H HOHHO OHO O O HH H + COO One carboxyl group assists the loss of the other. HOCCH 3 O

14. Dr. Wolf's CHM 201 & 202 19-14 Mechanism of Decarboxylation OOOHHO HH H HOHHO OHO O O HH H + COO One carboxyl group assists the loss of the other. HOCCH 3 O These hydrogens play no role.

15. Dr. Wolf's CHM 201 & 202 19-15 Mechanism of Decarboxylation OOOHHO RR' R R'OHHO OHO O O RR' H + COO One carboxyl group assists the loss of the other. HOCCHR' O Groups other than H may be present. R

16. Dr. Wolf's CHM 201 & 202 19-16185°C Decarboxylation is a general reaction for 1,3-dicarboxylic acids 160°C CO 2 H H (74%) (96-99%) CH(CO 2 H) 2 CH 2 CO 2 H

17. Dr. Wolf's CHM 201 & 202 19-17 Mechanism of Decarboxylation OOOHHO RR' R R'OHHO OHO O O RR' H + COO One carboxyl group assists the loss of the other. This OH group plays no role. HOCCHR' OR

18. Dr. Wolf's CHM 201 & 202 19-18 Mechanism of Decarboxylation OOOHR" RR' R COO One carboxyl group assists the loss of the other. Groups other than OH may be present. R"CCHR' OR OO O RR' H R" R'OH+ R"

19. Dr. Wolf's CHM 201 & 202 19-19 Mechanism of Decarboxylation OOOHR" RR' This kind of compound is called a  -keto acid.   R"CCHR' OR Decarboxylation of a  -keto acid gives a ketone.

20. Dr. Wolf's CHM 201 & 202 19-20 Decarboxylation of a  -Keto Acid C CH 3 C O CH 3 CO 2 H 25°C CO 2 C CH 3 C O CH 3 H +

21. Dr. Wolf's CHM 201 & 202 19-21 Section 19.18 Spectroscopic Analysis of Carboxylic Acids

22. Dr. Wolf's CHM 201 & 202 19-22 A carboxylic acid is characterized by peaks due to OH and C=O groups in its infrared spectrum. C=O stretching gives an intense absorption near 1700 cm -1. OH peak is broad and overlaps with C—H absorptions. Infrared Spectroscopy

23. Dr. Wolf's CHM 201 & 202 19-23200035003000250010001500500 Wave number, cm -1 Figure 19.8 Infrared Spectrum of 4-Phenylbutanoic acid C=O O—H and C—H stretch monosubstituted benzene C 6 H 5 CH 2 CH 2 CH 2 CO 2 H

24. Dr. Wolf's CHM 201 & 202 19-24 proton of OH group of a carboxylic acid is normally the least shielded of all of the protons in a 1 H NMR spectrum: (  10-12 ppm; broad). 1 H NMR

25. Dr. Wolf's CHM 201 & 202 19-25 Chemical shift ( , ppm) Figure 19.9 CH 2 CH 2 CH 2 COH O 01.02.03.04.05.06.07.08.09.010.0 11.012.0

26. Dr. Wolf's CHM 201 & 202 19-26 13 C NMR Carbonyl carbon is at low field (  160-185 ppm), but not as deshielded as the carbonyl carbon of an aldehyde or ketone (  190-215 ppm).

27. Dr. Wolf's CHM 201 & 202 19-27 UV-VISUV-VIS Carboxylic acids absorb near 210 nm, but UV-VIS spectroscopy has not proven to be very useful for structure determination of carboxylic acids.

28. Dr. Wolf's CHM 201 & 202 19-28 Aliphatic carboxylic acids undergo a variety of fragmentations. Aromatic carboxylic acids first form acylium ions, which then lose CO. Mass Spectrometry ArCOH O ArCOH +O ArC O + Ar+

29. Dr. Wolf's CHM 201 & 202 19-29 End of Chapter 19