Propionic Acid

[79-09-4]  · C3H6O2  · Propionic Acid  · (MW 74.09)

(catalyst for orthoester Claisen rearrangement;1 solvent for malonate diester decarboxylation13 and porphyrin synthesis14)

Alternate Name: propanoic acid.

Physical Data: clear liquid, bp 141 °C, 40 °C/10 mmHg; mp -23 °C; d 0.993 g cm-3.1

Solubility: miscible with water, ethanol, ether, chloroform.

Form Supplied in: neat liquid; commercially available.

Analysis of Reagent Purity: by titrimetric assay; carbonyl compound impurity tests are known.15

Purification: usually by repeated fractional distillation.16

Handling, Storage, and Precautions: corrosive organic acid with an acrid odor. It is especially destructive to tissue of mucous membranes and upper respiratory tract, eyes, and skin. Inhalation is a major hazard and may be fatal. Use of a NIOSH/MSHA approved respirator is recommended. Use gloves, eye protection, and protective clothing to avoid contact. The acid should never be mixed with basic solvents, oxidizers, and reducing agents. Use in a fume hood.

Orthoester Claisen Rearrangement.

Propionic acid is the classic acid catalyst for the Johnson orthoester Claisen rearrangement of an allylic alcohol and trialkyl orthoester (see Triethyl Orthoacetate). Examples have been reported for all allylic bond substitutions, including 1,1-disubstituted (eq 1),2 (E),3 (Z),4 trisubstituted,5 and tetrasubstituted.6

The reaction of a propargyl alcohol and triethyl orthoacetate produces an allene ester (eq 2).7 Allenic alcohols react in a similar manner to give diene esters in moderate yield (eq 3).8

The reaction of 2-butynediol with excess trimethyl orthopropionate and catalytic propionic acid yields a symmetrical diene diester through the novel double Claisen orthoester rearrangement (eq 4).9

Other Variations on the Orthoester Claisen Rearrangement.

The condensation of a dialkyl acetal and a primary allylic alcohol to form an unsaturated ketone has been catalyzed with propionic acid (eq 5).10 The condensation of an allylic alcohol with Triethyl Methanetricarboxylate yields, after decarboxylation, an unsaturated ester (eq 6).11

Decarboxylation of Malonic Esters.

The decarboxylation of malonic ester derivatives to esters is general in propionic acid (eq 7).12 This reaction is complementary to the basic hydrolysis of malonate esters to carboxylic acids.

Synthesis of Porphyrins.

The condensation of an aldehyde and pyrrole in propionic acid leads to the formation of a tetrasubstituted porphyrin.13 In an improved porphyrin synthesis, 2-acylpyrroles are reduced to the corresponding alcohols and converted to porphyrins by condensation and oxidation in refluxing propionic acid (eq 8).14

Related Reagents.

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

1. The Sigma-Aldrich Library of Chemical Safety Data, 2nd ed.; Lenga, R. E., Ed.; Sigma-Aldrich: Milwaukee, 1988; vol. 2, p 2957.
2. (a) Johnson, W. S.; Werthemann, L.; Bartlett, W. R.; Brocksom, T. J.; Li, T.; Faulkner, D. J.; Petersen, M. R. JACS 1970, 92, 741. (b) Henrick, C. A.; Schaub, F.; Siddall, J. B. JACS 1972, 94, 5374.
3. Tadano, K.; Shimada, K.; Miyake, A.; Ishihara, J.; Ogawa, S. BCJ 1989, 62, 3978.
4. Nishikimi, Y.; Iimori, T.; Sodeoka, M.; Shibasaki, M. JOC 1989, 54, 3354.
5. (a) Tadano, K. I.; Idogaki, Y.; Yamada, H.; Suami, T. JOC 1987, 52, 1201. (b) Tadano, K. I.; Ishihara, J.; Yamada, H.; Ogawa, S. JOC 1989, 54, 1223.
6. Taguchi, T.; Morikawa, T.; Kitagawa, O.; Mishima, T.; Kobayashi, Y. CPB 1985, 33, 5137.
7. (a) Dauben, W. G.; Shapiro, G. JOC 1984, 49, 4252. (b) Crandall, J. K.; Tindell, G. L. CC 1970, 1411. (c) Henderson, M. A.; Heathcock, C. H. JOC 1988, 53, 4736.
8. (a) Behrens, U.; Wolff, C.; Hoppe, D. S 1991, 644. (b) Sleeman, M. J.; Meehan, G. V. TL 1989, 30, 3345.
9. Ishino, Y.; Nishiguchi, I.; Kim, M.; Hirashima, T. S 1982, 9, 740.
10. (a) Daub, G. W.; Lunt, S. R. TL 1983, 24, 4397. (b) Daub, G. W.; Sanchez, M. G.; Cromer, R. A.; Gibson, L. L. JOC 1982, 47, 743.
11. Kulkarni, M. G.; Sebastian, M. T. SC 1991, 21, 581.
12. Brown, R. T.; Jones, M. F. JCR(S) 1984, 332.
13. Datta-Gupta, N.; Malakar, D.; Jenkins, C.; Strange, C. BCJ 1988, 61, 2274.
14. Kuroda, Y.; Murase, H.; Suzuki, Y.; Ogoshi, H. TL 1989, 30, 2411.
15. Reagent Chemicals: American Chemical Society Specifications, 8th ed.; American Chemical Society: Washington, 1993; pp 606-608.
16. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd. ed.; Pergamon: New York, 1988; p 264.

Kirk F. Eidman

Scios Nova, Baltimore, MD, USA

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