Pivalic Acid

[75-98-9]  · C5H10O2  · Pivalic Acid  · (MW 102.15)

(hindered Brønsted acid)

Alternate Names: 2,2-dimethylpropanoic acid; trimethylacetic acid.

Physical Data: mp 35.5 °C; bp 163.8 °C, 78 °C/20 mmHg, 72 °C/0.1 mmHg; pKa 5.04 (25 °C).1

Solubility: sol EtOH, ether, H2O (2.5 g 100 mL-1 at 25 °C).1

Form Supplied in: crystalline solid (needles). The sodium salt hydrate is also available.

Preparative Methods: from the bromoform reaction on pinacolone or from t-butyl chloride, Magnesium, and Carbon Dioxide; recent improvements involve the reaction of t-BuCl, Lithium, and magnesium 2-ethoxyethoxide.14

Purification: fractionally distilled in vacuo; recrystallized from benzene.15

Handling, Storage, and Precautions: corrosive and can cause burns; it should be treated with the same precautions as Acetic Acid.

Acid Catalyst for Asymmetric Reductions.

Investigations into the use of asymmetrically modified Raney Nickel for asymmetric hydrogenations have revealed that the use of pivalic acid as catalyst often provides superior optical yields. In a study of the reduction of 2-octanone to 2-octanol over tartaric acid-Sodium Bromide-modified Raney nickel, use of a THF/carboxylic acid mixture as the reaction medium resulted in a substantial increase in the optical yield; pivalic acid gave the highest optical yield.2 In subsequent studies,3,4 the reduction of a variety of methyl ketones via catalytic hydrogenation over modified Raney nickel in the presence of pivalic acid provided the corresponding (S)-RCH(OH)Me compounds in optical yields of 63-80%.

Acid Catalyst for Rearrangements.

When guaiacol and triethyl orthoacrylate were reacted in refluxing benzene using Propionic Acid as a catalyst, only 50% of the desired Claisen rearrangement/ring closure product was obtained, due to esterification of the catalyst. Use of the more hindered pivalic acid furnished the desired product in quantitative yield (eq 1);5 see also Sato et al.6 and Dorsey et al.7

Regioselective Protonation of Enolates.

In a study of the regioselectivity of protonation of allenyl enolates, pivalic acid demonstrated superior selectivity; in the example shown (eq 2),8 allene (1), resulting from protonation at C-2, was formed exclusively when the intermediate enolate was quenched with pivalic acid at -80 °C.8,9

Generation of t-Butyl Radicals via Oxidative Decarboxylation.

Silver-catalyzed decarboxylation of carboxylic acids by persulfate generates alkyl radicals, which have been used for homolytic alkylation of aromatic bases. Pivalic acid is a source of t-butyl radicals in this process. 2-t-Butylquinoline is formed regioselectively by this method (eq 3);10 6-t-butylnicotine has been prepared in a similar way.11

Preparation of 2-t-Butylpyrimidines.

2-t-Butylpyrimidines are precursors for 2-t-butylpyrimidinyl thiophosphates, which are active insecticides. Syntheses of these compounds from butyldiamines and pivalic acid have recently been described.12,13

Related Reagents.

Acetic Acid; Hydrochloric Acid; Propionic Acid; p-Toluenesulfonic Acid; Trifluoroacetic Acid; 2,4,6-Trimethylbenzoic Acid.

1. The Merck Index, 11th ed.; Budavari, S., Ed.; Merck: Rahway, NJ, 1989; p 1193.
2. Osawa, T.; Harada, T. CL 1982, 315.
3. Osawa, T.; Harada, T. BCJ 1984, 57, 1518.
4. Osawa, T. CL 1985, 1609.
5. Panetta, J. A.; Rapoport, H. JOC 1982, 47, 946.
6. Sato, H.; Kuromaru, K.; Ishizawa, T.; Aoki, B.; Koga, H. CPB 1992, 40, 2597.
7. Dorsey, B. D.; Plzak, K. J.; Ball, R. G. TL 1993, 34, 1851.
8. Krause, N. CB 1990, 123, 2173.
9. Krause, N.; Handke, G. TL 1991, 32, 7229.
10. Fontana, F.; Minisci, F.; Barbosa, M. C. N.; Vismara, E. T 1990, 46, 2525.
11. Seeman, J. I.; Clawson, L. E.; Secor, H. V. S 1985, 953.
12. Hull, J. W.; Otterson, K.; Rhubright, D. JOC 1993, 58, 520.
13. Hull, J. W.; Otterson, K. JOC 1992, 57, 2925.
14. (a) Puntambeker, S. V.; Zoellner, E. A. OS 1928, 8, 104; OSC 1941, 1, 524. (b) Sandborn, L. T.; Bousquet, E. W. OS 1928, 8, 108; OSC 1941, 1, 526. (c) Screttas, C. G.; Steele, B. R. JOC 1989, 54, 1013.
15. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: Oxford, 1988; p 261.

Gregory S. Hamilton

Scios Nova, Baltimore, MD, USA

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