PHOSPHORIC ACID
1
Phosphoric Acid
H
3
PO
4
[7664-38-2]
H
3
O
4
P
(MW 98.00)
InChI = 1/H3O4P/c1-5(2,3)4/h(H3,1,2,3,4)/f/h1-3H
InChIKey = NBIIXXVUZAFLBC-UGMYVIKVCK
(acid catalyst; dehydrating agent; phosphorylating agent
1
)
Physical Data:
mp 41
◦
C; bp 158
◦
C.
Solubility:
sol water, formic acid, acetic acid.
Form Supplied in:
commercially available; low melting white
solid or colorless liquid.
Analysis of Reagent Purity:
titration.
Preparative Method:
anhydrous H
3
PO
4
can be prepared by dis-
solving P
2
O
5
in 85% H
3
PO
4
.
Purification:
dry at 150
◦
C. At temperatures above 200
◦
C, mono-
meric H
3
PO
4
changes to oligomeric metaphosphoric acid.
Handling, Storage, and Precautions:
corrosive.
Introduction. Phosphoric acid is a strong, nonoxidizing acid
that is available in a number of different forms. Anhydrous, mono-
meric H
3
PO
4
(orthophosphoric acid) is a low melting solid
that can be purchased commercially or prepared by adding
P
2
O
5
to commercial 85% aqueous H
3
PO
4
. This combination has
been used to iodinate alcohols, cleave ethers, and hydroiodinate
alkenes, in addition to a variety of uses listed below.
2
Metaphos-
phoric acid [37267-86-0] is an oligomeric form, also commer-
cially available.
3
Hydrolysis of Imines, Amides, and Nitriles. The hydrolysis
of imines,
4
amides, and nitriles to carboxylic acids (eq 1) using
H
3
PO
4
is a time-honored technique.
5
There are numerous meth-
ods for accomplishing this transformation.
6
Ph CN
Ph CO
2
H
100% H
3
PO
4
155 °C, 4 h
(1)
70–90%
Preparation of Phosphates.
1
Phosphate mono- and dialkyl
esters have been prepared from phosphoric acid (see also Phos-
phorus Oxychloride). Treatment of (1) with H
3
PO
4
at rt provides
the corresponding phosphate in good yield (eq 2).
7
At high tem-
peratures, diesterification can occur (eq 3).
8
N
HCl
HO
NH
2
•HCl
OH
N
HCl
HO
NH
2
•HCl
O
P
OH
O
OH
100% H
3
PO
4
25 °C
(2)
(1)
70%
H
3
PO
4
, K
2
CO
3
xylene, 195 °C
HO
O
P
O
HO
(3)
2
76%
An effective, large-scale synthesis of diammonium acetylphos-
phate has been developed, and involves direct acylation of H
3
PO
4
.
Either ketene
9
or acetic anhydride
10
(eq 4) can be used in this
process.
O
O
O
O
P
O
O
ONH
4
ONH
4
1. H
3
PO
4
, EtOAc, 0 °C
2. NH
3
, MeOH, –30 °C
(4)
86%
Acid Cyclization Catalyst. A common use for H
3
PO
4
, as
a solution in water, a liquid acid, or in anhydrous form, is as
an acid cyclization catalyst. Cyclization of cross-conjugated ke-
tones in H
3
PO
4
/formic acid leads to 2,3-dialkylcyclopentenones
(eq 5) rather than the 3,4-dialkyl products expected of the Nazarov
cyclization.
11
This result is obtained when either the ketone or the
corresponding ethylene acetal is used as starting material. Similar
results are obtained using HBr/HOAc, although, in these exam-
ples, some of the 3,4-dialkyl products are obtained as well.
O
Et
Et
O
Et
Et
H
3
PO
4
, HCO
2
H
90 °C, 3 h
(5)
77%
An intermolecular example of an alkene-cation addition reac-
tion provides access to chromenes through isoprenylation of a
phenol (eq 6).
12
HO
OH
OH
O
O
OH
OH
O
H
3
PO
4
, xylene
78%
(6)
Cyclization of (2) in phosphoric acid results in an azabicy-
clononane (eq 7).
13
85% H
3
PO
4
(7)
N
N
(2)
73%
Phosphoric acid-mediated condensation of indole derivatives
with ketones provides access to 3-substituted indoles (eq 8).
14
N
H
MeO
N
O
Me
N
H
MeO
N
Me
(8)
88%
2N H
3
PO
4
Cyclization of enol acetates (eq 9), δ,ε-unsaturated aldehydes,
15
and ketene dithioacetals (eq 10) can also be accomplished by
heating in H
3
PO
4
. The cyclization of (3) results in dithiopy-
ridines by way of an intramolecular Ritter reaction followed by a
1,3-methylthio shift. Lewis acids, Boron Trifluoride Etherate in
particular, lead to simple dehydration.
16
Avoid Skin Contact with All Reagents
