FORMIC ACID

1

Formic Acid

1

HCO

2

H

[64-18-6]

CH

2

O

2

(MW 46.03)

InChI = 1/CH2O2/c2-1-3/h1H,(H,2,3)/f/h2H
InChIKey = BDAGIHXWWSANSR-QEZKKOIZCL

(formation of formate esters,

3

amides;

7

reductions;

10

transfer

hydrogenation;

12

rearrangements

22

)

Alternate Name:

methanoic acid.

Physical Data:

strongest of the simple organic acids; pK

a

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 C

6

H

6

.

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 titra-

tion 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

CuSO

4

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 chemi-
cal apron should be worn during all operations with concen-
trated 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.

HO

H

H

H

O

Ac

OH

O

H

H

H

O

Ac

OH

O

H

98% formic acid

benzene

(1)

85%

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

HO

O

O

H

(2)

petroleum

ether

formic acid, 22 °C

93%

O

H

H

O

(3)

98% formic acid

reflux

90%

HO

O

O

H

(4)

1. DCC, cat CuCl

2. formic acid
toluene, reflux

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 com-
pounds, including benzimidazoles (eq 5)

8

and triazoles (eq 6).

9

NH

2

NH

2

N
H

N

formic acid

(5)

reflux

HN

NH

NH

2

NH

2

N

N
H

N

NH

2

(6)

formic acid

cat H

2

SO

4

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 For-
mate) (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

Avoid Skin Contact with All Reagents

2

FORMIC ACID

N

O

Bn

N

CO

2

H

Bn

(7)

HN

O

H

formic acid

CO

2

H

CO

2

H

NH

3

, 100 °C

87%

O

O

Ph

O

O

NH

HN

Ph

(8)

H

2

N

NH

2

formic acid

ethanol

75%

Catalytic Transfer Hydrogenation.

12

Catalytic transfer

hydrogenation uses a metal catalyst and an organic hydro-
gen 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 α,β-unsaturated aldehydes and acids

13

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 result-

ing 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.

CO

2

H

(9)

CO

2

H

formic acid

Pd

0

100%

O

BnO

O

OH

HO

O

Pd

0

/C

formic acid

(10)

OBn

HO

MeOH, 22 °C

O

BnHN

H

O

H

2

N

(11)

H

Pd

0

formic acid

MeOH

95%

N

N
H

O

O

O

2

N

H

2

N

H

H

H

H

H

H

(12)

10% Pd

0

/C

formic acid

reflux

76–94%

The Rupe Rearrangement.

Tertiary propargyl alcohols

isomerize to α,β-unsaturated ketones in the Rupe rearrangement

(eq 13).

21

The reaction has been reviewed.

22

Formic acid is the

most common catalyst employed.

HO

OH

HO

O

(13)

formic acid

62%

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., Chem. Rev. 1969, 69, 673.

2.

Encyclopedia of Industrial Chemical Analysis

; Snell, F. D.; Etter, L. S.,

Eds.; Interscience: New York, 1971; Vol. 13, p 125.

3.

Hilscher, J.-C., Chem. Ber. 1981, 114, 389.

4.

Kozar, L. G.; Clark, R. D.; Heathcock, C. H., J. Org. Chem. 1977, 42,
1386.

5.

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Synth., Coll. Vol. 1973

, 5, 852.

6.

Kaulen, J., Angew. Chem., Int. Ed. Engl. 1987, 26, 773.

7.

Fieser, L. F.; Jones, J. E., Org. Synth., Coll. Vol. 1955, 3, 590.

8.

(a) Wagner, E. C.; Millett, W. H., Org. Synth., Coll. Vol. 1943, 2, 65.
(b) Mathias, L. J.; Overberger, C. G., Synth. Commun. 1975, 5, 461.

9.

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78

, 2858.

10.

(a) Moore, M. L., Org. React. 1949, 5, 301. (b) Stoll, A. P.; Niklaus, P.;
Troxler, F., Helv. Chim. Acta 1971, 54, 1988.

11.

Mosher, W. A.; Piesch, S., J. Org. Chem. 1970, 35, 1026.

12.

(a) Johnstone, R. A. W.; Wilby, A. H., Chem. Rev. 1985, 85, 129.
(b) Brieger, G.; Nestrick, T. J., Chem. Rev. 1974, 74, 567.

13.

(a) Elamin, B.; Park, J.-W.; Means, G. E., Tetrahedron Lett. 1988, 29,
5599. (b) Cortese, N. A.; Heck, R. F., J. Org. Chem. 1978, 43, 3985.

14.

(a) Araki, Y.; Mokubo, E.; Kobayashi, N.; Nagasawa, J., Tetrahedron
Lett. 1989

, 30, 1115. (b) Rao, V. S.; Perlin, A. S., Carbohydr. Res. 1980,

83

, 175.

15.

(a) Roush, W. R.; Walts, A. E., J. Am. Chem. Soc. 1984, 106, 721.
(b) Wang, C.-L. J.; Ripka, W. C.; Confalone, P. N., Tetrahedron Lett.
1984, 25, 4613. (c) El Amin, B.; Anantharamaiah, G. M.; Royer, G. P.;
Means, G. E., J. Org. Chem. 1979, 44, 3442.

16.

(a) Leonard, N. J.; Morrice, A. G.; Sprecker, M. A., J. Org. Chem. 1975,
40

, 356. (b) Morrice, A. G.; Sprecker, M. A.; Leonard, N. J., J. Org.

Chem. 1975

, 40, 363. (c) Entwistle, I. D.; Jackson, A. E.; Johnstone,

R. A. W.; Telford, R. P., J. Chem. Soc., Perkin Trans. 1 1977, 443.

17.

(a) Taylor, E. C.; Barton, J. W.; Osdene, T. S., J. Am. Chem. Soc. 1958,
80

, 421. (b) Moore, J. A.; Marascia, F. J., J. Am. Chem. Soc. 1959, 81,

6049.

18.

Schneller, S. W.; Christ, W. J., J. Org. Chem. 1981, 46, 1699.

19.

Kikugawa, Y.; Kashimura, M., Synthesis 1982, 785.

20.

Pandey, P. N.; Purkayastha, M. L., Synthesis 1982, 876.

21.

(a) Newman, M. S.; Goble, P. H., J. Am. Chem. Soc. 1960, 82, 4098.
(b) Takeshima, T., J. Am. Chem. Soc. 1953, 75, 3309.

22.

Swaminathan, S.; Narayanan, K. V., Chem. Rev. 1971, 71, 429.

23.

Reagent Chemicals: American Chemical Society Specifications

, 8th ed.;

American Chemical Society: Washington, 1993; p 348.

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

A list of General Abbreviations appears on the front Endpapers