BORIC ACID

1

Boric Acid

H

3

BO

3

[10043-35-3]

H

3

BO

3

(MW 61.83)

InChI = 1/BH3O3/c2-1(3)4/h2-4H
InChIKey = KGBXLFKZBHKPEV-UHFFFAOYAI

(reacts with alcohols to form borate esters;

1

catalyzes

dehydration,

2

hydrolysis,

3

decarboxylation,

4

and condensation

reactions;

5

useful in carbohydrate chemistry

6

)

Physical Data:

mp 169

◦

C; d 1.435 g cm

−3

. Heating boric acid

above 100

◦

C gradually produces metaboric acid, HBO

2

; at

higher temperatures all water is lost and boron oxide, B

2

O

3

,

results.

Solubility:

sol cold water (1 g in 18 mL), boiling water (1 g in

4 mL), cold alcohol (1 g in 18 mL), boiling alcohol (1 g in 6
mL), glycerol (1 g in 6 mL), acetone (1 g in 15 mL).

Form Supplied in:

white solid, widely available (see also Sodium

Tetraborate).

Purification:

recrystallize three times from water (3 mL g

−1

)

with filtering. Dry over metaboric acid in a desiccator.

Handling, Storage, and Precautions:

boric acid is hygroscopic. It

is an irritant to eyes, skin, and mucous membranes, and should
be handled with the appropriate precautions to eliminate contact
with these areas. Death has resulted from ingestion of 5 to 20 g
in adults. Use in a fume hood.

Borate Esters.

Trigonal borate esters are readily formed

by condensing alcohols with boric acid; the reaction is driven
by azeotropic removal of water. Borate esters are stable under
a variety of anhydrous reaction conditions and can serve as a
method of protecting alcohols.

1

The reactivity of carbonyl com-

pounds can be enhanced by intramolecular coordination with an
adjacent borate ester.

7

Borate esters are intermediates in boric

acid-catalyzed dehydrations of primary, secondary, and tertiary
alcohols.

2

Carbocation-derived rearrangements are a potential

problem with this method.

8

Imine Hydrolysis. Imines can be hydrolyzed in quantitative

yields by using boric acid in refluxing ethanol.

3

Imines that are sus-

ceptible to intra- and intermolecular attack in the presence of other
catalysts have been successfully hydrolyzed using boric acid.

9

Conversion of isoxazolines into β-hydroxy ketones and β-hydroxy
esters involves hydrogenolysis of the N–O bond and imine hydrol-
ysis in a single step.

10

In the presence of boric acid, racemization

is inhibited (eq 1).

10a

O

N

O

OH

O

OH

H

2

(1 atm)

Raney Ni

+

(1)

(2)

(1)

Additive (2–5 equiv)

acetate

phosphate

boric acid

(1)

91
94

100

(2)

9
6
0

:

:
:
:

MeOH–H

2

O

(5:1)

>90%

Decarboxylation. Boric acid has been used to catalyze the

decarboxylation of β-keto esters and β-imino esters.

4,11

A con-

venient method for the production of γ-keto esters from diethyl
α

-acylsuccinates in high yield is shown in eq 2.

4

The conven-

tional method of saponification, decarboxylation, and reesterifi-
cation produced low yields.

80%

O

R

OEt

O

O

OEt

O

R

O

OEt

1. H

3

BO

3

170 °C, 1.5 h

(2)

2. H

2

O

Condensation.

Boric acid catalyzes the self-condensation

of aldehydes and ketones to produce α,β-unsaturated enones.

12

Yields were much higher than those reported with other acid or
base catalysts. Under similar conditions, aldehydes which are not
readily susceptible to aldol condensation, dismutate to form esters
(Tischenko reaction).

13

A catalytic amount of boric acid/sulfuric

acid mixture has been used to synthesize aryl esters (eq 3) in
good yields.

5

The reaction was unsuccessful using mineral acids

or boric acid alone.

(3)

RCO

2

H

+

ArOH

H

2

SO

4

, H

3

BO

3

(1–5 mol%)

eight examples

RCO

2

Ar

xylene, reflux

–H

2

O

58–94%

Indole can be condensed directly with various carboxylic acids

in the presence of boric acid.

14

Traditional methods were found

to be unsatisfactory due to low yields and the production of 3-
acylated and 1,3-diacylated side products.

Carbohydrate Chemistry. In alkaline solution, boric acid cat-

alyzes the isomerization of aldoses into ketoses.

6

During the syn-

thesis of mono- and diacylglycerides, the use of boric acid to re-
move acetal

15

and trityl

16

protecting groups minimizes undesired

acyl group migrations.

17

The reductive acetylation of azidopy-

ranosides to form N-acetylaminopyranosides is improved in the
presence of boric acid.

18

1.

Fanta, W. I.; Erman, W. F., Tetrahedron Lett. 1969, 4155.

2.

(a) Majerski, Z.; Škare, D.; Vuli´c, L., Synth. Commun. 1986, 16, 51.
(b) Bubnov, Yu. N.; Grandberg, A. I.; Grigorian, M. Sh.; Kiselev, V. G.;
Struchkova, M. I.; Mikhailov, B. M., J. Organomet. Chem. 1985, 292,
93. (c) Campbell, J. R. B.; Islam, A. M.; Raphael, R. A., J. Chem. Soc
1956, 4096.

3.

(a) Barton, D. H. R.; Jaszberenyi, J. Cs.; Theodorakis, E. A., J. Am. Chem.
Soc. 1992

, 114, 5904. (b) Matsuda, H.; Nagamatsu, H.; Okuyama, T.;

Fueno, T., Bull. Chem. Soc. Jpn. 1984, 57, 500.

4.

Wehrli, P. A.; Chu, V., J. Org. Chem. 1973, 38, 3436.

5.

Lowrance, W. W., Jr., Tetrahedron Lett. 1971, 3453.

6.

Mendicino, J. F., J. Am. Chem. Soc. 1960, 82, 4975

7.

(a) Takeuchi, I.; Hamada, Y.; Okamura, K., Heterocycles 1989, 29, 2109.
(b) Morita, S.; Otsubo, K.; Uchida, M.; Kawabata, S.; Tamaoka, H.;
Shimizu, T., Chem. Pharm. Bull. 1990, 38, 2027.

8.

Chapman, O. L.; Borden, G. W., J. Org. Chem. 1961, 26, 4193.

9.

(a) Ouazzani, F.; Roumestant, M.-L.; Viallefont, P., Tetrahedron:
Asymmetry 1991

, 2, 913. (b) Trost, B. M.; Li, L.; Guile, S. D., J. Am.

Chem. Soc. 1992

, 114, 8745.

Avoid Skin Contact with All Reagents

2

BORIC ACID

10.

(a) Curran, D. P., J. Am. Chem. Soc. 1983, 105, 5826. (b) Curran, D. P.;
Fenk, C. J., Tetrahedron Lett. 1986, 4865. (c) Duclos, O.; Mondange, M.;
Duréault, A.; Depezay, J. C., Tetrahedron Lett. 1992, 8061. (d) Calderola,
P.; Ciancaglione, M.; De Amici, M.; De Micheli, C., Tetrahedron Lett.
1986, 4647.

11.

(a) Ho, T. L., Synth. Commun. 1979, 9, 609. (b) Bacos, D.; Celerier, J.-P.;
Lhommet, G., Tetrahedron Lett. 1987, 2353.

12.

Offenhauer, R. D.; Nelsen, S. F., J. Org. Chem. 1968, 33, 775.

13.

Stapp, P. R., J. Org. Chem. 1973, 38, 1433.

14.

Terashima, M.; Fujioka, M., Heterocycles 1982, 19, 91.

15.

Strawn, L. M.; Martell, R. E.; Simpson, R. U.; Leach, K. L.; Counsell,
R. E., J. Med. Chem. 1989, 32, 643.

16.

(a) Strawn, L. M.; Martell, R. E.; Simpson, R. U.; Leach, K. L.; Counsell,
R. E., J. Med. Chem. 1989, 32, 2104. (b) van Boeckel, C. A. A.; van
Boom, J. H., Tetrahedron 1985, 41, 4545.

17.

Gunstone, F. D. In Comprehensive Organic Chemistry; Barton, D. H. R.;
Ollis, W. D., Eds.; Pergamon: Oxford, 1979; Vol. 5, p 648.

18.

(a) Broxterman, H. J. G.; van der Marel, G. A.; van Boom, J. H., J.
Carbohydr. Chem. 1991

, 10, 215. (b) Hiroyuki, I.; Ogawa, T., Carbohydr.

Res. 1989

, 186, 107.

Bradley D. Smith & Martin Patrick Hughes

University of Notre Dame, Notre Dame, IN, USA

A list of General Abbreviations appears on the front Endpapers