Formic Acid1


[64-18-6]  · CH2O2  · Formic Acid  · (MW 46.03)

(formation of formate esters,3 amides;7 reductions;10 transfer hydrogenation;12 rearrangements22)

Alternate Name: methanoic acid.

Physical Data: strongest of the simple organic acids; pKa 3.77 (4.77 for acetic acid). Pure acid, mp 8.4 °C; bp 100.7 °C, 50 °C/120 mmHg, 25 °C/40 mmHg. Formic acid and water form an uncommon maximum boiling azeotrope, bp 107.3 °C, containing 77.5% acid. The dielectric constant of formic acid is 10 times greater than acetic acid.

Solubility: misc water in all proportions; misc EtOH, ether; mod sol C6H6.

Form Supplied in: commercially available as 85-95% aqueous solutions and as glacial formic acid, containing 2% water.

Analysis of Reagent Purity: formic acid is determined by titration with base. If other acids are present, formic acid content can be determined by a redox titration based on oxidation with potassium permanganate. Methods for analysis of trace organic and inorganic materials are presented.2,23

Purification: fractional distillation in vacuo; dehydration over CuSO4 or boric anhydride.24

Handling, Storage, and Precautions: the strongly acidic nature of formic acid is the primary safety concern. Contact with the skin will cause immediate blistering. Immediately treat affected areas with copious amounts of water. Do not use dilute base solutions as a first treatment. Formic acid has a large heat of solution; the combined heat of neutralization and dilution will lead to thermal burns. Eye protection, gloves, and a chemical apron should be worn during all operations with concentrated formic acid. Volatile; vapors will cause intense irritation to mouth, nose, eyes, skin, and upper respiratory tract. Use of an appropriate NIOSH/MSHA respirator is recommended. Use in a fume hood.

During storage, glacial formic acid decomposes to form water and carbon monoxide. Pressure can develop in sealed containers and may result in rupture of the vessel. Ventilation should be provided to prevent the buildup of carbon monoxide in storage areas. Storage temperatures above 30 °C should be avoided.

Formic acid is incompatible with strong oxidizing reagents, bases, and finely powdered metals, furfuryl alcohol, and thallium nitrate. Contact with conc sulfuric acid will produce carbon monoxide from decomposition.

Formation of Formate Esters.

Formic acid will esterify primary, secondary, and tertiary alcohols in high yield (eq 1).3 The reaction is autocatalytic due to the high acidity of formic acid. The equilibrium position of this reaction is closer to completion than for other carboxylic acids.

Formate esters can also be produced during acid-catalyzed rearrangements (eq 2),4 by addition to alkenes (eq 3),5 or by 1,3-Dicyclohexylcarbodiimide coupling (eq 4).6

Formation of Amides.

Most amines react with formic acid to produce the expected amide in high yield.7 Reaction with diamines is an important reaction for the formation of heterocyclic compounds, including benzimidazoles (eq 5)8 and triazoles (eq 6).9

Reductions with Formic Acid.

Formic acid is unique among the simple organic acids in its ability to react as a reducing agent. Ketones are reduced and converted to primary amines by reaction with ammonia and formic acid (see Ammonium Formate) (eq 7).10 Ketones or aldehydes will react with formic acid and primary or secondary amines to produce secondary or tertiary amines (eq 8).10a,11

Catalytic Transfer Hydrogenation.12

Catalytic transfer hydrogenation uses a metal catalyst and an organic hydrogen donor as a stoichiometric reducing agent. This is a useful laboratory alternative to normal catalytic reduction, as the use of flammable hydrogen gas is avoided. Formic acid and amine formates are common hydrogen donors. Formic acid has been used to reduce a,b-unsaturated aldehydes and acids13 to the saturated compounds (eq 9). Benzyl ethers (eq 10)14 and benzyl amines (eq 11)15 are cleaved by transfer hydrogenation with formic acid. A variety of nitrogen functions are reduced including the nitro group,16 azo group,17 hydrazines,18 and enamines.19 The resulting amines will be formylated under the reaction conditions; use of water or alcohol as solvent will limit formylation. If the reduction results in a suitable diamine, formylation will lead to heterocycle formation (eq 12).16a Aromatic halides are reduced to the aromatic hydrocarbon.20 See also Palladium-Triethylamine-Formic Acid.

The Rupe Rearrangement.

Tertiary propargyl alcohols isomerize to a,b-unsaturated ketones in the Rupe rearrangement (eq 13).21 The reaction has been reviewed.22 Formic acid is the most common catalyst employed.

Related Reagents.

For uses of other carboxylic acids in synthesis, see Acetic Acid, Acrylic Acid, Glyoxylic Acid, Oxalic Acid, Methanesulfonic Acid and Trifluoroacetic Acid.

1. Gibson, H. W. CRV 1969, 69, 673.
2. Encyclopedia of Industrial Chemical Analysis; Snell, F. D.; Etter, L. S., Eds.; Interscience: New York, 1971; Vol. 13, pp 125-131.
3. Hilscher, J.-C. CB 1981, 114, 389.
4. Kozar, L. G.; Clark, R. D.; Heathcock, C. H. JOC 1977, 42, 1386.
5. Kleinfelter, D. C.; Schleyer, P. v. R. OS 1962, 42, 79; OSC 1973, 5, 852.
6. Kaulen, J. AG(E) 1987, 26, 773.
7. Fieser, L. F.; Jones, J. E. OSC 1955, 3, 590.
8. (a) Wagner, E. C.; Millett, W. H. OSC 1943, 2, 65. (b) Mathias, L. J.; Overberger, C. G. SC 1975, 5, 461.
9. Elion, G. B.; Lange, W. H.; Hitchings, G. H. JACS 1956, 78, 2858.
10. (a) Moore, M. L. OR 1949, 5, 301. (b) Stoll, A. P.; Niklaus, P.; Troxler, F. HCA 1971, 54, 1988.
11. Mosher, W. A.; Piesch, S. JOC 1970, 35, 1026.
12. (a) Johnstone, R. A. W.; Wilby, A. H. CRV 1985, 85, 129. (b) Brieger, G.; Nestrick, T. J. CRV 1974, 74, 567.
13. (a) Elamin, B.; Park, J.-W.; Means, G. E. TL 1988, 29, 5599. (b) Cortese, N. A.; Heck, R. F. JOC 1978, 43, 3985.
14. (a) Araki, Y.; Mokubo, E.; Kobayashi, N.; Nagasawa, J. TL 1989, 30, 1115. (b) Rao, V. S.; Perlin, A. S. Carbohydr. Res. 1980, 83, 175.
15. (a) Roush, W. R.; Walts, A. E. JACS 1984, 106, 721. (b) Wang, C.-L. J.; Ripka, W. C.; Confalone, P. N. TL 1984, 25, 4613. (c) El Amin, B.; Anantharamaiah, G. M.; Royer, G. P.; Means, G. E. JOC 1979, 44, 3442.
16. (a) Leonard, N. J.; Morrice, A. G.; Sprecker, M. A. JOC 1975, 40, 356. (b) Morrice, A. G.; Sprecker, M. A.; Leonard, N. J. JOC 1975, 40, 363. (c) Entwistle, I. D.; Jackson, A. E.; Johnstone, R. A. W.; Telford, R. P. JCS(P1) 1977, 443.
17. (a) Taylor, E. C.; Barton, J. W.; Osdene, T. S. JACS 1958, 80, 421. (b) Moore, J. A.; Marascia, F. J. JACS 1959, 81, 6049.
18. Schneller, S. W.; Christ, W. J. JOC 1981, 46, 1699.
19. Kikugawa, Y.; Kashimura, M. S 1982, 785.
20. Pandey, P. N.; Purkayastha, M. L. S 1982, 876.
21. (a) Newman, M. S.; Goble, P. H. JACS 1960, 82, 4098. (b) Takeshima, T. JACS 1953, 75, 3309.
22. Swaminathan, S.; Narayanan, K. V. CRV 1971, 71, 429.
23. Reagent Chemicals: American Chemical Society Specifications, 8th ed.; American Chemical Society: Washington, 1993; pp 348-350.
24. Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory Chemicals, 3rd ed.; Pergamon: New York, 1988; p 185.

Kirk F. Eidman

Scios Nova, Baltimore, MD, USA

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