Propanal hydroamination with p-aminobenzoic acid

Article abstract of DOI:10.1134/S1070428010050052

The propanal hydroamination was studied. It was found that the reaction in ethanol proceeded faster than in 2-propanol. By ¹H and ¹³C NMR method the existence was proved of a tautomeric equilibrium in ethanol solution between 4-(propylideneamino)benzoic acid and its enamine form, 4-(prop-1-en-1-ylamino)benzoic acid. Pleiades Publishing, Ltd., 2010.

Full text of DOI:10.1134/S1070428010050052

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 5, pp. 634−636. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © N.A. Magdalinova, T.G. Volkova, M.V. Klyuev, M.S. Gruzdev, 2009, published in Zhurnal Organicheskoi Khimii, 2010,
Vol. 46, No. 5, pp. 646−648.
Propanal Hydroamination with p-Aminobenzoic Acid
N.A. Magdalinovaa, T.G. Volkovaa, M.V. Klyueva, and M.S. Gruzdevb
aIvanovo State University, Ivanovo, Russia
b Institute of Solution Chemistry, Russian Academy of Sciences, Ivanovo, 153045 Russia e-mail: mn2408@mail.ru
Received November 19, 2008
Abstract—The propanal hydroamination was studied. It was found that the reaction in ethanol proceeded
1
faster than in 2-propanol. By H and 13C NMR method the existence was proved of a tautomeric
equilibrium in ethanol solution between 4-(propylideneamino)benzoic acid and its enamine form, 4-
(prop-1-en-1-ylamino)benzoic acid.
DOI: 10.1134/S1070428010050052
Among versatile amines unsymmetrical secondary
amines that exhibit uncommon chemical and biological
properties are especially interesting [1, 2]. One of the
general methods of the synthesis of these amines is the
catalytic hydrogenating amination of aldehydes. The
absence of harmful side products in this process compar-
ed, for instance, with the synthesis of these products using
halo derivatives, permits regarding this reaction as
a “green” method [3]. In this connection the continuation
of the study of the hydrogenating amination of a series
of aliphatic and heterocyclic aldehydes with aromatic,
alicyclic, or heterocyclic amines or their precursors leading
to the formation of unsymmetrical secondary amines is
urgent.
were nearly twice larger in ethanol than in 2-propanol,
and we attribute it to the higher polarity of the ethanol as
well as the structural features of 2-propanol molecules.
The azomethine formed as an intermediate product
can be involved in the solution into a prototropic triade
tautomerism (the proton migration between the extremes
of the triade, the system of three atoms among which two
are connected by a double bond, occurs with the shift of
the double bond) [5]. In order to study this tautomerism
the azomethine, 4-(propylideneamino)benzoic acid, was
synthesized by the propanal condensation with the
p-aminobenzoic acid at heating in ethanol solution. The
1
azomethine structure was confirmed by IR, H, and
13C NMR spectra in DMSO-d6. In the solution of 4-(prop-
ylideneamino)benzoic acid in DMSO-d6–C2D5OD, 1:0.2,
a tautomeric equilibrium azomethineA' enamine B was
observed. In the 1H NMR spectrum two separate proton
signals were observed: of azomethine group N=CH (s,
7.66 ppm) and of enamine group NCH=CH (d, 6.62 ppm).
These hydrogen atoms are specific for each tautomer,
therefore the ratio of their intensity characterizes the ratio
of the imine and enamine forms in the solution. The ratio
of the integral intensity of the said signals was 1: 1. The
stabilization of the enamine form was favored by ethanol
as a polar protic solvent [6, 7].
The target of this study was the investigation of
propanal hydroamination with p-aminobenzoic acid
including the kinetics of the process.
The hydrogenating amination of propanal with 4-
amino-benzoic acid was carried out under mild conditions
at 25–45°C and the atmospheric pressure of hydrogen in
two solvents (2-propanol and ethanol) in the presence of
a catalyst (1% Pd/C). The kinetic and activation param-
eters are presented in the table. The hydroamination
proceeded in the kinetic range as shows the Thiele
criterion (0.01–0.06 depending on conditions) and was
of the zero order with respect to the reagents and of the
first order in hydrogen and catalyst according to the data
of [4]. It turned out that the hydroamination was faster
in ethanol and possessed a lower activation energy, but
more negative entropy. The rate constants of the reaction
1
The analysis of IR, H and 13C NMR spectra of the
hydroamination product showed that the formed compound
was a secondary aliphatic-aromatic amine. In the 1H NMR
spectrum of the reduced product of reaction I compared
with the initial compoundsAand B was found the lack of
634

PROPANAL HYDROAMINATION WITH p-AMINOBENZOIC ACID
635
Kinetic and energy characteristics of hydroamination
a singlet at 7.66 (N=CH) and a doublet at 6.62ppm
(NCH=CH). Also a displacement was observed of the
aromatic protons signals belonging to tautomersAand B
to the strong field in the region 6.10–8.20 ppm and an
appearance of a multiplet at 2.96 ppm from the reduced
CH2 group indicating the increase in the number of
protons by two in the final compound.
kapp
The presence in solution of an equilibrium between
the sufficiently stable tautomeric forms suggests that the
final product, the secondary amine, may form by reduction
of both azomethine and enamine. The problem, whether
the hydrogenation proceeds concurrently with both
tautomers or the reduction suffers mainly the more
reactive one (with a shift of the equilibrium) requires
additional investigation.
a
The error in the determination of the rate constant amounted on the
average to 4–5%.
B), 130.45 (2C, CHAr,A), 149.63 (CHN, B), 151.55 (CArN,
A), 158.13 (HC=N, A), 168.89 (COOH, A, B).
EXPERIMENTAL
4-(Propylamino)benzoic acid (I). To a solution of
0.232 g (4 mmol) of propanal in 10 ml of ethanol was
added 0.548 g (4 mmol) of p-aminobenzoic acid dissolved
in 10 ml of ethanol. The mixture was heated at 45°C for
30 min and cooled to 22°C. In a flow of hydrogen 0.2 g
(1% Pd) of catalyst Pd/C was charged into the reactor
under a cover with a layer of 5 ml of ethanol, the catalyst
was activated with hydrogen for 10 min, then the freshly
prepared reaction mixture was introduced into the reactor,
and the hydrogenation was carried out for 8 h. The formed
precipitate was dissolved in ethanol at heating, and the
reaction mixture was filtered from the catalyst. On cooling
the filtrate the separated precipitate was filtered off on
a glass frit, washed with ethanol, and dried in air. Yield
0.645 g (90%). Colorless crystals, mp 166–168°C [8].
IR spectrum, ν, cm–1: 3402 (NH), 3065 (CHAr), 2968,
2932, 2876 (CHAlk), 1918 (Ar–N), 1668 (C=O), 1602 (C–
N), 1527, 1482, 1458, 1422, 1383 (Ar), 1347, 1335, 1317,
1301, 1283, 1244 (CHAlk), 1178, 1148, 1088, 1031, 1003,
962, 929 (CO), 868, 832, 772, 700, 676, 637, 607 (CHAr).
1H NMR spectrum (DMSO-d6), δ, ppm: 0.95 t (3H, CH3),
2.02 m (2H, CH2), 2.96 m (2H, CH2N), 6.75–7.78 m
(4H, C6H4), 9.72 s (1H, HN–C). 13C NMR spectrum
(DMSO-d6), δ, ppm: 16.03 (CH3), 22.17 (CH2), 60.20
(CH2N), 118.71 (2C, CHAr), 121.98 (CAr), 132.91 (2C,
CHAr), 154.62 (CArN), 169.67 (COOH).
IR spectra were registered on a spectrophotometer
IR-Vertex 80 Bruker in the range 4000–400 cm–1 from
1
pellets with KBr. H and 13C NMR spectra were
recorded on spectrometers Bruker AC-200 (200.13 and
50.32 ΜHz respectively) and BrukerAvance-500 (500.13
and 400.32 ΜHz respectively), internal reference TMS.
4-(Propylideneamino)benzoic acid. To a solution
of 0.232 g (4 mmol) of propanal in 10 ml of ethanol was
added 0.548 g (4 mmol) of p-aminobenzoic acid dissolved
in 10 ml of ethanol. The mixture was heated at 45°C for
30 min, cooled to 22°C, and maintained at this temperature
for 3 h. The separated precipitate was filtered off, washed
with ethanol, and dried in air. Yield 0.65 g (92%). Colorless
crystals, mp 208–210°C. IR spectrum, ν, cm–1: 3065
(CHAr), 2968, 2933, 2876 (CHAlk), 1918 (Ar–N), 1672
(C=O), 1619 (C=N), 1527, 1488, 1461, 1416, 1383 (Ar),
1338, 1317, 1284, 1244, 1226 (CHAlk), 1178, 1148, 1088,
1034, 1004, 958, 925 (CO), 868, 835, 775, 700, 673, 652,
637, 604 (CHAr). 1H NMR spectrum (DMSO-d6), δ, ppm:
0.95 t (3H, CH3), 1.72 m (2H, CH2), 6.60–7.80 m (4H,
C6H4), 7.64 s (1H, HC=N). 13C NMR spectrum
(DMSO-d6), δ, ppm: 18.75 (CH3), 22.67 (CH2), 121.30
(2C, CHAr), 130.67 (CAr), 132.37 (2C, CHAr), 150.25
1
(CArN), 158.07 (HC=N), 168.85 (COOH). H NMR
spectrum (DMSO-d6–C2D5OD), δ, ppm: 0.96 t (3H, CH3,
A), 1.11 t (3H, CH3, B), 1.72 m (2H, CH2, A), 3.44 m
(1H, CHCH3, B), 6.60–7.80 m (4H, C6H4, A, B), 6.62 d
(1H, CH=C, B) 9.72 s (1H, NHC, B). 13C NMR spectrum
(DMSO-d6–C2D5OD), δ, ppm: 18.65 (CH3, A, B), 22.60
(CH2, A), 98.44 (CHCH3, B), 111.77 (2C, CHAr, B),
118.02 (CAr, B), 121.24 (2C, CHAr,A), 129.99 (2C, CHAr,
Procedure of kinetic measurements and
calculations. The hydrogenating amination was carried
out by procedure [4] in a glass reactor equipped with
a magnetic stirrer under temperature control at 298, 308,
318 K and hydrogen pressure of 1 at. In a flow of
hydrogen 0.2 g (1% Pd) of catalyst Pd/C was charged
into the reactor under a cover with a layer of 5 ml of
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 5 2010

MAGDALINOVA et al.
636
solvent (2-propanol, ethanol), the catalyst was activated
with hydrogen for 10 min, then in a flow of hydrogen the
previously prepared reaction mixture (2 mmol of p-amino-
benzoic acid and 2 mmol of propanal dissolved in 20 ml
of the solvent) was introduced into the reactor and the
hydrogenation was performed at constant vigorous
stirring. The apparent reaction rate was measured by
the volume of consumed hydrogen every 5 min:
where A, Β, C are coefficient from the Handbook [9], T
is the temperature of the experiment, K.
The hydrogen concentration was calculated from the
hydrogen solubility in the solvent with accounting for
Henry constant H, Pa m–3 mol–1 [10].
The study was carried out under a financial support
of the Ministry of Education and Science of the Russian
Federation in the framework of the project “Development
of the integration mechanism for Ivanovo State University
and the Institute of the Problems of Chemical Physics of
the Russian Academy of Sciences” (RNP.2.2.1.1.2820).
VH2
/
,
wa
=
Vmol
V
s
60
where wa is the apparent reaction rate, mol l–1 s–1; VH is
the consumed volume of hydrogen (ml) over time inter2val
ô, min; Vmol is the molar volume, ml/mol; Vs is the solvent
volume, l.
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p
wa
,
k
k
app
eff
=
[
] [
]
cat
H2
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where [H2] is the hydrogen concentration, mol l–1, [cat]
is the catalyst concentration, g-at Pd l–1; p is the correction
factor accounting for the internal partial pressure of the
solvent vapor:
_
pat
p
s
,
p
=
760
where pat is the atmospheric pressure at the time of the
experiment, mm Hg; ps is the pressure of the solvent
vapor at the temperature of the experiment, mm Hg,
calculated byAntoin equation [9]:
10. Luhring, P. and Schumpe, A., J. Chem. Eng. Data., 1989,
vol. 34, p. 250.
ln ps = A + B/(T + C);
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 5 2010