The reaction of para-aminobenzoic acid with 1-iodopropan-2-one

Full text of DOI:10.1134/S1070363216080314

ISSN 1070-3632, Russian Journal of General Chemistry, 2016, Vol. 86, No. 8, pp. 1961–1963. © Pleiades Publishing, Ltd., 2016.
Original Russian Text © L.V. Zhilitskaya, N.О. Yarosh, L.G. Shagun, I.А. Dorofeev, L.I. Larina, 2016, published in Zhurnal Obshchei Khimii, 2016, Vol. 86,
No. 8, pp. 1387–1389.
LETTERS
TO THE EDITOR
The Reaction of para-Aminobenzoic Acid
with 1-Iodopropan-2-one
L. V. Zhilitskaya*, N. О. Yarosh, L. G. Shagun, I. А. Dorofeev, and L. I. Larina
Favorskii Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
*e-mail: lara_zhilitskaya@irioch.irk.ru
Received April 14, 2016
Keywords: para-aminobenzoic acid, 1-iodopropan-2-one, alkylation, triiodide
DOI: 10.1134/S1070363216080314
Derivatives of p-aminobenzoic acid are of practical
interest due to their diverse biological activity [1–8],
stimulating the search for the synthesis routes towards
new representatives of this class of compounds and
investigation of their properties.
(50°С) in the absence of solvent, the alkylation also
proceeded at the amino group, giving rise to mono-
iodide А (route а). However, О-alkylation with the
formation of adduct В occurred at room temperature
(route b). Further, iodide anions of the adducts А and
В entered the reaction with molecular iodine formed
due to the reduction of iodoketone 2 with hydrogen
iodide, the latter being evolved during the alkylation;
that process led to the earlier unknown triiodides of 4-
carboxy-N-(2-oxopropyl)phenylammonium 4 or 4-[(2-
oxopropoxy)carbonyl]phenylammonium 5 in 41 and
49% yield, respectively (Scheme 2).
In the literature, numerous methods for functio-
nalization of p-aminobenzoic acid are described, based
on the reactions with alkyl or acyl halides with the
formation of the products of N-alkylation; the reactions
are favored in alkaline media. Modification of the N-
substituted derivatives of p-aminobenzoic acid pro-
ceeds in the presence of sodium hydride in DMF and
gives the products of O- and N-alkylation [4, 5]. To
our knowledge, the data on functionalization of amino-
benzoic acids with α-iodoketones have been absent.
Low yields of triiodides 4 and 5 were apparently
due to the competing reaction of polycondensation of
acid 1, leading to a mixture of oligopeptides that we
failed to separate.
In this present work we studied for the first time the
reaction of p-aminobenzoic acid 1 with 1-iodopropan-
2-one 2 at different temperature, both in the presence
and in the absence of solvent and bases. The reaction
in an aqueous–acetone solution of Na2CO3 both at
room temperature and on heating (50°С) results in the
formation of exclusively 4-(2-oxopropyl)aminobenzoic
acid 3 (Scheme 1).
Triiodides 4, 5 were dense oils; upon formation,
they act as a solvent affording the homogeneous
reaction mixture.
Structure and composition of compounds 3–5 were
1
confirmed by the data of elemental analysis, Н, 13С,
and 15N NMR and UV spectroscopy. The 15N HMBC
{1H–15N} spectrum of 4-(2-oxopropyl)aminobenzoic
acid 3 contained the cross peaks of the nitrogen atom
at –304 ppm and the ortho-protons of the benzene ring
It turned out that in the absence of base the course
of the reaction depended on temperature. On heating
Scheme 1.
O
O
Na2CO3
CH3
CH2
H2N
CH3
NH
I
C
O
_NaI
OH
OH
O
2
1
3
1961

1962
ZHILITSKAYA et al.
Scheme 2.
2
6
3
O
OH
O
O
I3
I
1
4
I2
a
H2N
H2N
H2N
OH
OH
5
O
O
1
A
4
CH3
O
O
O
O
2
I
H3N
H3N
I3
I2
O
2
b
I
O
O
5
B
I
2
HI
I2
I3
Me2C=O
1
and the СН2 group. The same spectrum of compound 4
contained cross peaks of the nitrogen atom at
–175.1 ppm and both the ortho-protons of the ring and
the methylene protons, whereas the spectrum of
compound 5 contained a cross peak of the nitrogen
atom (–328 ppm) only with the ortho-protons of the
aromatic ring.
mp 191–193°С. Н NMR spectrum (DMSO-d6), δ,
ppm: 2.10 s (3Н, СН3), 4.04 s (2Н, СН2), 6.57 d (2Н,
Н2,6 J = 8.8 Hz), 7.65 d (2Н, Н3,5 J = 8.8 Hz). 13С
NMR spectrum (DMSO-d6), δС, ppm: 27.33 (СН3),
52.79 (СН2), 111.53 (С2,6), 117.86 (С4), 131.39 (С3,5),
152.25 (С1), 167.87 (СОО), 206.03 (С=О). Found, %:
С 62.57; Н 5.43; N 7.31. C10H11NO3. Calculated, %: С
62.17; Н 5.74; N 7.25.
UV spectra of triiodides 4 and 5 contained the
absorption bands with maximums at 291–292 and
362–364 nm, typical of I3– anion [9].
Reaction of p-aminobenzoic acid with 1-iodo-
propan-2-one. A suspension of 0.2 g (1.5 mmol) of p-
aminobenzoic acid 1 and 0.55 g (3 mmol) of
iodoketone 2 was stirred at 20°С for 72 h or at 45°С
for 6 h. After the completion of the reaction, the dense
oil was dissolved in 10 mL of acetonitrile, and 50 mL
of diethyl ether was added. The formed precipitate of
oligopeptides was separated by filtration. The filtrates
containing triiodides 4 and 5 were evaporated and
purified by column chromatography on a column with
MN Kieselgel 60 silica (0.063–0.2 mm) using acetone
as eluent.
N-Alkylation of acid 1 at room temperature in the
presence of Na2CO3, unlike O-alkylation in the absence
of the base, was apparently due to the formation of the
salt and the increase in the basicity of the amino group
owing to a weakened conjugation with the negatively
charged substituent СОО–. The reasons of the
temperature dependence of the course of the reaction
require a separate investigation.
In summary, depending on the conditions of the
reaction, alkylation of p-aminobenzoic acid with 1-
iodopropan-2-one occurs either at the amino or the
carboxyl group.
4-Carboxy-N-(2-oxopropyl)phenylammonium (4).
Yield 0.18 g (41%), Rf 0.87 (acetone). Н NMR spec-
1
trum (acetone-d6), δ, ppm: 2.33 s (3Н, СН3), 4.28 s
(2Н, СН2), 7.75 d (2Н, Н3,5 J = 8.3 Hz), 8.19 d (2Н,
Н2,6 J = 8.3 Hz), 8.59 s (2Н, NH2). 13С NMR spectrum
(acetone-d6), δС, ppm: 27.77 (СН3), 65.83 (СН2),
114.20 (С2,6), 125.87 (С4), 130.59 (С3,5), 133.57 (С1),
166.10 (СОО), 197.60 (С=О). Found, %: С 20.54; Н
1.92; N 2.18; I 66.08. C10H12I3NO3. Calculated, %: С
20.89; Н 2.10; N 2.44; I 66.22.
4-(2-Oxopropyl)aminobenzoic acid (3). 1 eq./L
solution of Na2CO3 was added to a solution of 0.2 g
(1.5 mmol) of p-aminobenzoic acid 1 in 2 mL of
distilled water to рН 8. Then, a solution of 0.26 g
(1.5 mmol) of iodoketone 2 in 1 mL of acetone was
added dropwise at stirring. After completion of the
reaction (2 h at 20°С or 20 min at 50°С), the
precipitate was filtered off, washed with water, and
dried in vacuum. Yield 0.25 g (85%), white powder,
4-[(2-Oxopropoxy)carbonyl]phenylammonium
triiodide (5). Yield 0.21 g (49%), Rf 0.85 (acetone). 1Н
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 8 2016

THE REACTION OF para-AMINOBENZOIC ACID
NMR spectrum (acetonitrile-d3 ), δ, ppm: 2.31 s (3Н,
REFERENCES
1963
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 86 No. 8 2016