PROPIONIC ACID 1
O
Propionic Acid
(MeO)3CEt
MeO
HO
cat propionic acid
(4)
CO2H 3 h, 50 110 °C
OH
distill methanol
OMe
88%
O
[79-09-4] C3H6O2 (MW 74.09)
InChI = 1/C3H6O2/c1-2-3(4)5/h2H2,1H3,(H,4,5)/f/h4H
InChIKey = XBDQKXXYIPTUBI-JLSKMEETCG
Other Variations on the Orthoester Claisen Rearrange-
(catalyst for orthoester Claisen rearrangement;1 solvent for
ment. The condensation of a dialkyl acetal and a primary allylic
malonate diester decarboxylation13 and porphyrin synthesis14)
alcohol to form an unsaturated ketone has been catalyzed with pro-
pionic acid (eq 5).10 The condensation of an allylic alcohol with
Alternate Name: propanoic acid.
Triethyl Methanetricarboxylate yields, after decarboxylation, an
ć% ć%
Physical Data: clear liquid, bp 141 C, 40 C/10 mmHg; mp
unsaturated ester (eq 6).11
ć%
-23 C; d 0.993 g cm-3.1
Solubility: miscible with water, ethanol, ether, chloroform.
Form Supplied in: neat liquid; commercially available.
cat propionic acid
+
OH
Analysis of Reagent Purity: by titrimetric assay; carbonyl com-
24 h, 120 °C
MeO OMe
pound impurity tests are known.15 69%
Purification: usually by repeated fractional distillation.16
Handling, Storage, and Precautions: corrosive organic acid with
O
an acrid odor. It is especially destructive to tissue of mucous
membranes and upper respiratory tract, eyes, and skin. Inhala-
(5)
tion is a major hazard and may be fatal. Use of a NIOSH/MSHA
OMe
approved respirator is recommended. Use gloves, eye protec-
O
tion, and protective clothing to avoid contact. The acid should
never be mixed with basic solvents, oxidizers, and reducing
(EtO)3CMe
agents. Use in a fume hood.
cat propionic acid
OEt
HC(CO2Et)3 +
3 h, 140 °C
HO (6)
O
74%
Orthoester Claisen Rearrangement. Propionic acid is the
classic acid catalyst for the Johnson orthoester Claisen rearrange-
Decarboxylation of Malonic Esters. The decarboxylation of
ment of an allylic alcohol and trialkyl orthoester (see Triethyl
malonic ester derivatives to esters is general in propionic acid
Orthoacetate). Examples have been reported for all allylic bond
(eq 7).12 This reaction is complementary to the basic hydrolysis
substitutions, including 1,1-disubstituted (eq 1),2 (E),3 (Z),4 tri-
of malonate esters to carboxylic acids.
substituted,5 and tetrasubstituted.6
propionic acid
O CO2Et CO2Et
(7)
cat propionic acid
48 h, reflux
(EtO)3CMe
EtO CO2Et
85%
(1)
HO 1 h, 138 °C
Synthesis of Porphyrins. The condensation of an aldehyde
The reaction of a propargyl alcohol and triethyl orthoacetate
and pyrrole in propionic acid leads to the formation of a tetra-
produces an allene ester (eq 2).7 Allenic alcohols react in a similar
substituted porphyrin.13 In an improved porphyrin synthesis, 2-
manner to give diene esters in moderate yield (eq 3).8
acylpyrroles are reduced to the corresponding alcohols and con-
cat propionic acid verted to porphyrins by condensation and oxidation in refluxing
OEt
(EtO)3CMe
propionic acid (eq 8).14
(2)
1 h, 100 °C
OH
" O
4 h, 180 °C
R
O
O
propionic acid
(EtO)3CMe
N
N
R
reflux, O2
cat propionic aci
O N
Zn (8)
R
" O N
R
N
0.25 equiv Zn(OAc)2
20 h, 140 °C (3)
O
OH
H N
N
OH
OMe
R
The reaction of 2-butynediol with excess trimethyl orthopropi-
onate and catalytic propionic acid yields a symmetrical diene di-
ester through the novel double Claisen orthoester rearrangement Related Reagents. Acetic Acid; Pivalic Acid; p-Toluenesul-
(eq 4).9 fonic Acid; Trifluoroacetic Acid; 2,4,6-Trimethylbenzoic Acid.
Avoid Skin Contact with All Reagents
2 PROPIONIC ACID
1. The Sigma Aldrich Library of Chemical Safety Data, 2nd ed.; Lenga, R. 9. Ishino, Y.; Nishiguchi, I.; Kim, M.; Hirashima, T., Synthesis 1982, 9,
E., Ed.; Sigma Aldrich: Milwaukee, 1988; Vol. 2, p 2957. 740.
2. (a) Johnson, W. S.; Werthemann, L.; Bartlett, W. R.; Brocksom, T. J.; Li, 10. (a) Daub, G. W.; Lunt, S. R., Tetrahedron Lett. 1983, 24, 4397. (b) Daub,
T.; Faulkner, D. J.; Petersen, M. R., J. Am. Chem. Soc. 1970, 92, 741. G. W.; Sanchez, M. G.; Cromer, R. A.; Gibson, L. L., J. Org. Chem. 1982,
(b) Henrick, C. A.; Schaub, F.; Siddall, J. B., J. Am. Chem. Soc. 1972, 47, 743.
94, 5374.
11. Kulkarni, M. G.; Sebastian, M. T., Synth. Commun. 1991, 21, 581.
3. Tadano, K.; Shimada, K.; Miyake, A.; Ishihara, J.; Ogawa, S., Bull.
12. Brown, R. T.; Jones, M. F., J. Chem. Res. (S) 1984, 332.
Chem. Soc. Jpn. 1989, 62, 3978.
13. Datta-Gupta, N.; Malakar, D.; Jenkins, C.; Strange, C., Bull. Chem. Soc.
4. Nishikimi, Y.; Iimori, T.; Sodeoka, M.; Shibasaki, M., J. Org. Chem.
Jpn. 1988, 61, 2274.
1989, 54, 3354.
14. Kuroda, Y.; Murase, H.; Suzuki, Y.; Ogoshi, H., Tetrahedron Lett. 1989,
5. (a) Tadano, K. I.; Idogaki, Y.; Yamada, H.; Suami, T., J. Org. Chem.
30, 2411.
1987, 52, 1201. (b) Tadano, K. I.; Ishihara, J.; Yamada, H.; Ogawa, S.,
15. Reagent Chemicals: American Chemical Society Specifications, 8th ed.;
J. Org. Chem. 1989, 54, 1223.
American Chemical Society: Washington, 1993; p 606.
6. Taguchi, T.; Morikawa, T.; Kitagawa, O.; Mishima, T.; Kobayashi, Y.,
16. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals,
Chem. Pharm. Bull. 1985, 33, 5137.
3rd Ed.; Pergamon: New York, 1988; p 264.
7. (a) Dauben, W. G.; Shapiro, G., J. Org. Chem. 1984, 49, 4252.
(b) Crandall, J. K.; Tindell, G. L., J. Chem. Soc., Chem. Commun. 1970,
Kirk F. Eidman
1411. (c) Henderson, M. A.; Heathcock, C. H., J. Org. Chem. 1988, 53,
Scios Nova, Baltimore, MD, USA
4736.
8. (a) Behrens, U.; Wolff, C.; Hoppe, D., Synthesis 1991, 644. (b) Sleeman,
M. J.; Meehan, G. V., Tetrahedron Lett. 1989, 30, 3345.
A list of General Abbreviations appears on the front Endpapers