Kinetic parameters of the intramolecular condensation of diphenylamine-2-carboxylic acid under microwave radiation

Article abstract of DOI:10.1134/S1070363212010240

The cyclization of diphenylamine-2-carboxylic acid under microwave radiation was investigated. The kinetic parameters of the processes were measured. The use of microwave radiation was found to reduce the reaction duration and to increase the target produ

Full text of DOI:10.1134/S1070363212010240

ISSN 1070-3632, Russian Journal of General Chemistry, 2012, Vol. 82, No. 1, pp. 149–152. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © Yu.D. Markovich, T.N. Kudryavtseva, M.I. Brylev, V.Yu. Markovich, I.A. Koroleva, 2012, published in Zhurnal Obshchei Khimii,
2012, Vol. 82, No. 1, pp. 152–155.
Kinetic Parameters of the Intramolecular Condensation
of Diphenylamine-2-carboxylic Acid
under Microwave Radiation
Yu. D. Markovich, T. N. Kudryavtseva, M. I. Brylev, V. Yu. Markovich, and I. A. Koroleva
Southwestern State University, ul. 50 Let Octyabrya 94, Kursk, 305040 Russia
e-mail: kstu-oah@yandex.ru
Received October 28, 2010
Abstract—The cyclization of diphenylamine-2-carboxylic acid under microwave radiation was investigated.
The kinetic parameters of the processes were measured. The use of microwave radiation was found to reduce
the reaction duration and to increase the target product yield. The optimal conditions for processes were
determined.
DOI: 10.1134/S1070363212010240
The investigation of the possibility of using
microwave radiation in the synthesis of various
heterocyclic compounds is an urgent task, as this
method has several advantages over the other types of
activation of the chemical reaction: reducing the
reaction duration, high energetic efficiency of the
process, etc. [1, 2].
Among the affordable ways of getting the majority
of acridones is the cyclization of appropriate acid I in
concentrated sulfuric acid at 90–100°C for 4 h, the
recommended mole ratio of diphenylamine-2-
carboxylic acid : sulfuric acid is from 1:7.5 to 1:9 [4,
5]. It was interesting to compare the reaction rate and
yield for the reactions under the microwave and the
traditional conditions of heating.
The target products of condensation of substituted
diphenylamine-2-carboxylic acid (Ia–Ig) are the
acridones that are used as starting materials in the
synthesis of various drugs [3].
Under both microwave and traditional heating, the
cyclization reaction proceeds according to the scheme:
O
COOH
MW, H2SO4
R
R
N
H
N
H
I
II
R = H (а), 2'-CH3 (b), 3'-CH3 (c), 4'-CH3 (d), 2'-COOH (e), 4'-COOH (f), 2'-NO2 (g).
The use of sulfuric acid as a cyclizing agent favors
phenylamine-2-carboxylic acids we measured the
kinetic characteristics of the reaction. After processing
the chromatograms, we calculated the degree of
consumption of the initial acid I and the degree of
accumulation of the corresponding acridone (α = cI/cI0).
The kinetic curves of consumption of unsubstituted
acid Ia and accumulation of acridone and acrido-
nesulfonic acid in sulfuric acid at 90°C at the
side reactions of sulfonation. As shown by earlier
research [6], the use of microwave radiation increases
the yield of the mono- and disulfo-derivatives
(compounds IV and V, respectively):
To determine the effect of microwave heating on
the intramolecular condensation of substituted di-
149

150
MARKOVICH et al.
O
O
O
HO3S
SO3H
R
HO3S
H2SO4
H2SO4
R
R
N
H
IV
N
H
III
N
H
V
R = H (а), 4-CH3 (b), 1– and -3-CH3 (c), 2-CH3 (d), 4-COOH (e), 2-COOH (f), 4-NO2 (g).
traditional method of heating (a) and under the
microwave conditions (b) are presented in the figure.
database of mass spectra “NIST2005.” The spectra of
the acridones synthesized under the microwave radia-
tion and by the traditional method of heating are
identical [9]. The reaction conditions and yields of
target compounds at the traditional heating and micro-
wave radiation are listed in Table 2.
As shown in the figure, in the microwave the acid
Ia is consumed at a higher rate, and over a shorter
period of time. At the traditional heating the half-
period of the DFACA – acridone transformation is
60 min, while at the application of microwave heating
only 20 min. The same regularities are found for other
studied compounds.
As seen from Table 2, the effect of microwave
radiation on the acridone yield becomes most
noticeable at the cyclization of a diphenylamine-2-
carboxylic acid at lower temperatures.
We were able from the data obtained to determine
the reaction rate constants and to calculate therefrom
the activation energy of the process under the
microwave conditions and to compare the results with
those obtained with the traditional method of heating
(Table 1).
Thus, the use of microwave radiation as an
activator of the process of synthesis of substituted
acridones reduces reaction time and leads to a higher
yield of the target product,
EXPERIMENTAL
As seen from Table 1, the use of microwave
radiation significantly increases the rate of the
cyclization reaction and reduces the activation energy.
The studies were carried out using a laboratory
microwave installation MARS of CEM Corporation
with a temperature control system, at a microwave
power 400 W, the molar ratio diphenylamine-2-
carboxylic acid : sulfuric acid = 1:8.
The acridones obtained were isolated, their
structure was confirmed by the data of IR spectroscopy
and gas chromatography–mass spectrometry using a
α
α
(a)
(b)
1
2
3
τ, min
τ, min
Kinetic curves of the accumulation of (1) acridone IIa and (3) acridonesulfonic acid IIIa, and (2) the consumption of
diphenylamine-2-carboxylic acid Ia, in a medium of concentrated sulfuric acid at 90 ± 2°C at the traditional method of (a) heating
and (b) under microwave radiation.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 82 No. 1 2012

KINETIC PARAMETERS OF THE INTRAMOLECULAR CONDENSATION
151
Table 1. Kinetic parameters of the diphenylamine-2-carboxylic acids cyclization in concentrated sulfuric acid
Traditional heating [5, 8]
Microwave radiation
k×105, s–1 at Т (°С)
k×105, s–1 at Т (°С)
Acid
Еa,
Еa,
kJ mol–1
kJ mol–1
60
–
70
80
90
100
60
–
70
–
80
90
100
2.12±
0.08
6.88±
0.25
21.00±
0.81
56.30±
2.17
45.28±
1.81
116.5
121.3
127.9
99.0
12.17±
0.48
10.28±
0.40
254.90±
10.1
32.15±
1.28
16.72±
0.66
–
66.41±
2.64
31.56±
1.25
–
93.2
Ia
Id
Ie
If
–
–
1.37±
0.05
6.11±
0.24
14.92±
0.59
–
3.46±
0.13
43.12±
1.71
76.1
115.0
49.1
7.87±
0.31
27.79±
1.11
89.22± 294.00±
3.56
7.76±
0.31
11.76
–
7.51±
0.30
22.31±
0.89
61.28± 142.81±
2.45 2.45
19.33± 32.27±
0.77 1.28
52.02±
2.07
–
–
Table 2. Effect of the cyclization conditions on the yield of substituted acridones
Traditional heating
Microwave radiation
reaction duration, min yield, %
Temperature,
Acridone
°С
reaction duration, min
yield, %
90
120
90
240
10
76.2±0.5
73.4±0.6
53.0±0.5
71.3±0.7
78.2±0.7
78.5±0.5
120
10
86.6±0.6
85.6±0.7
65.5±0.7
77.7±0.5
78.4±0.5
84.4±0.4
IIa
120
120
90
120
120
30
IIb
IId
IIe
IIg
100
80
90
12
10
The kinetic studies were carried out using thin layer
chromatography with densimetry. Chromatograms
obtained were processed on a Sorbfil videodensimeter
at the 254 nm wavelength with the Sorbfil 1.8 program
[7].
was filtered off, treated with sodium carbonate solution
to remove traces of diphenylamino-2-carboxylic acid,
the precipitate was filtered off and dried at 90°C in an
oven with forced air circulation.
The composition of the reaction mixtures was
determined by TLC by comparison with reference
samples. (Plates “Sorbfil” PTSH-P-B-UV, eluent
The IR spectra were taken on a FT-IR spectrometer
Nicolet IR-200. The mass-spectrometric investigations
were carried out using a Thermo Scientific HPLC-MS
system.
toluene–acetone–ethanol–1% HCl in
7:6:5:0.5.
a ratio of
General procedure. To 0.047 mol of compound I
was added 20 ml (0.37 mol) of 93.4% sulfuric acid.
The mixture was stirred without heating until complete
dissolution of acid I. The reactor was placed in a
microwave system and the temperature in the reactor
was raised to the desired value. At regular intervals
samples were taken from the reaction mixture for
analysis of content of the parent acid and the reaction
products. Upon completion, the mixture was poured
into 300 ml of water heated to 80–90°C. The product
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