Catalytic Aminomethylation of Aminobenzamides with Bis(N,N-dimethylamino)methane and Carbamides

Article abstract of DOI:10.1134/S1070363219020063

An effective method was developed for the synthesis of acyclic aniline derivatives bearing carbamide fragments by the reaction of carbamides with ortho-, meta-, and para-aminobenzamides and bis(N,N-dimethylamino) methane in the presence of NiCl₂·6H₂O and SmCl₃·6H₂O as catalysts.

Full text of DOI:10.1134/S1070363219020063

ISSN 1070-3632, Russian Journal of General Chemistry, 2019, Vol. 89, No. 2, pp. 204–211. © Pleiades Publishing, Ltd., 2019.
Russian Text © R.R. Khairullina, T.V. Tyumkina, A.R. Geniyatova, F.K. Mullagil’dina, A.G. Ibragimov, 2019, published in Zhurnal Obshchei Khimii, 2019,
Vol. 89, No. 2, pp. 202–210.
Catalytic Aminomethylation of Aminobenzamides
with Bis(N,N-dimethylamino)methane and Carbamides
R. R. Khairullinaa*, T. V. Tyumkinaa, A. R. Geniyatovaa,
F. K. Mullagil’dinaa, and A. G. Ibragimova
a Institute of Petrochemistry and Catalysis of the Russian Academy of Sciences, pr. Oktyabrya 141, Ufa, 450075 Russia
*e-mail: ink@anrb.ru
Received July 12, 2018; revised July 12, 2018; accepted July 16, 2018
Abstract—An effective method was developed for the synthesis of acyclic aniline derivatives bearing
carbamide fragments by the reaction of carbamides with ortho-, meta-, and para-aminobenzamides and bis(N,N-
dimethylamino)methane in the presence of NiCl2·6H2O and SmCl3·6H2O as catalysts.
Keywords: aminomethylation, aminobenzamides, bis(N,N-dimethylamino)methane, carbamides
DOI: 10.1134/S1070363219020063
Aminomethylation reaction of acid amides with
formaldehyde and NH-acids is still the classical
method for the preparation of aminomethylated acid
amides [1–10]. We have shown that catalytic amino-
methylation of primary alkylamines [11] or aryl
carboxylic acid hydrazides [12] using bis(N,N-
dimethylamino)methane and (thio)urea or N,N'-bis[(di-
methylamino)methyl]-(thio)carbamides is a convenient
method for the synthesis of nitrogen-containing hetero-
cycles bearing carbamide fragments under mild
conditions.
methylaminomethyl)urea, N,N'-bis[(dimethylamino)-
methyl]allophanamide and N-({[(dimethylamino)-
methyl][(2-methylhydrazino)carbonyl]amino}methyl)-
N,N-dimethylamine in the presence of transition or rare-
earth metals catalysts.
Using the example of aminomethylation of ortho-
aminobenzamide with bis(N,N-dimethylamino)methane
and urea, it was found that among the tested catalysts
based on d- and f-elements, NiCl2·6H2O is better of
choice (67%, see table). When using the reagents ratio
ortho-aminobenzamide : bis(N,N-dimethylamino)methane :
urea : NiCl2·6H2O = 10 : 20 : 10 : 2, the reaction takes
place in EtOH at 70°C over 12 hours to form 2-({[({[(di-
methylamino)methyl]amino}carbonyl)amino]methyl}-
amino)benzamide 1 (Scheme 1).
Nitrogen-containing heterocycles with carbamide
fragments show antiviral and antibacterial activity
[13], are promising synthons for producing alkaloids
with antitumor properties [14, 15], as wells they are
used as pesticides [16] and fuels bioprotectors [17]. Amino-
benzamides and their derivatives are prospective
enzyme glucokinase activators [18, 19], luminescent
markers in biological systems [20], exhibit antitumor
[21–23] and antibacterial activity [24].
Aminomethylation of meta- and para-aminobenz-
amides with urea and bis(N,N-dimethylamino)methane
with the reagents ratio aminobenzamide : bis(N,N-
dimethylamino)methane : urea : NiCl2·6H2O = 10 :
20 : 10 : 2 in EtOH at 70°C for 24 hours leads to the
aminomethylated products 3 (64%) and 5 (70%,
Scheme 2).
Continuing the study of catalytic aminomethylation
reaction at the primary amino group [11, 12], herein
we reported an effective method for synthesizing N-
substituted aniline derivatives containing urea
fragments that are promising for practical use based on
the aminomethylation of ortho-, meta- and para-
aminobenzamides with use of bis(N,N-dimethylamino)
methane and some carbamides (urea, biuret,
semicarbazide hydrochloride), as well as N,N'-bis(di-
The minor products of the aminomethylation reac-
tion of aminobenzamides are 2(3,4)-amino-N-[(di-
methylamino)methyl]benzamides 2, 4 and 6 with
yields of no more than 10%. Their formation is
probably due to generation of aminobenzamide
complexes with NiCl2·6H2O [25] or SmCl3·6H2O,
204

CATALYTIC AMINOMETHYLATION OF AMINOBENZAMIDES
205
The effect of the nature of the solvent and the catalyst on the yield of compounds 1 and 2a
Yield of 1
Yield of 1
Catalyst
Solvent
EtOH
Catalyst
Solvent
(2), %
67 (5)
59 (8)
32 (5)
54 (4)
24 (5)
(2), %
15 (5)
5 (5)
5 (5)
5 (‒)
‒ (‒)
NiCl2·6H2O
Sm(NO3)3·6H2O
ZnCl2·2H2O
Cs2CO3
EtOH
''
EtOH–CHCl3
''
''
''
''
''
CHCl3
EtOH
''
Ni(NO3)2·6H2O
SmCl3·6H2O
CuCl2·2H2O
FeCl3·6H2O
а Reaction conditions: aminobenzamide : bis(N,N-dimethylamino)methane : carbamide : catalyst = 10 : 20 : 10 : 2, 70°С, EtOH, 12 h.
which undergoes aminomethylation with bis(N,N-di-
methylamino)methane at the amide group (Scheme 2).
In the absence of a catalyst, the reaction does not
proceed.
yield of compounds 7–9 is 11, 10, and 15%,
respectively, while the yield of 2(3,4)-amino-N-
[(dimethylamino)methyl]benzamides 2, 4 and 6 does
not exceed 20%.
Along with urea, biuret and semicarbazide hydro-
chloride were involved into the reaction of catalytic
aminomethylation of aminobenzamides with bis(N,N-
dimethylamino)methane. Under optimal conditions
[aminobenzamide : bis(N,N-dimethylamino)methane :
biuret : SmCl3·6H2O = 10 : 20 : 10 : 2, 70°C, EtOH,
12 h] aminomethylation of ortho-, meta- and para-
aminobenzamides results in acyclic derivatives of
aminobenzamides 7 (43%), 8 (40%) and 9 (51%,
Scheme 3). When NiCl2·6H2O is used as a catalyst, the
Aminomethylation with semicarbazide hydro-
chloride and bis(N,N-dimethylamino)methane using
SmCl3·6H2O as a catalyst under similar conditions
[aminobenzamide : bis(N,N-dimethylamino)methane :
semicarbazide hydrochloride : SmCl3·6H2O = 10 : 30 :
10 : 2, 70°C, EtOH, 24 h] leads to the formation of 3-
and 4-[({[(dimethylamino)methyl][(2-methylenehydra-
zino)carbonyl]amino}methyl) amino]benzamides 10
and 11 with yields of 58 and 36%, respectively.
Attempts to involve ortho-aminobenzamide into the
Scheme 1.
O
O
NH2
H2N
NH2
H2N
[Ni]
O
HN
NH2
+
−Me2NH
+
H
HN
NMe2
NMe2
Me2N
N
NH
NMe2
O
H2N
O
1, 3, 5
2, 4, 6
ortho (1, 2), meta (3, 4), para (5, 6).
Scheme 2.
NH2
H2N
H2
NMe2
−Me2NH
NMe2
O
N
Cl
Ni
Cl
O
.
HN
2, 4, 6
−NiCl2 6H2O
O
N
NMe2
H2
NH2
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 2 2019

206
KHAIRULLINA et al.
Scheme 3.
O
O
H2N
NH2
[Sm]
HN
NH2
+
2, 4, 6
+
NH2
−Me2NH
H
N
H
Me2N
N
NH
NMe2
NMe2
HN
O
O
O
H2N
O
7-9
ortho (7), meta (8), para (9).
Scheme 4.
O
Me2N
O
NH2
H
H
N
[Ni]
2, 4, 6
+
CH2
N
N
H2N
H2N
NMe2
N
NH2
−Me2NH
O
+
HN
NH2
O
10, 11
.
HCl
NMe2
meta (10), para (11).
aminomethylation reaction failed (Scheme 4). Amino-
methylation in the presence of NiCl2 ortho-amino-
benzamide provides the reaction products 10 and 11 in
40 and 29% yield, respectively. Under these condi-
tions, the yield of aminomethylated products 2, 4, and
6 does not exceed 30%; in the absence of a catalyst,
the aminomethylation reaction does not proceed.
methyl)-N,N-dimethylamine 14 by aminomethylation
of carbamides with bis(N,N-dimethylamino)methane
[carbamide : bis(N,N-dimethylamino)methane : SmCl3·
6H2O = 10 : 10 : 0.5, 80°C, EtOH, 8 h] (Scheme 5)
[11].
N,N'-Bis(dimethylaminomethyl)carbamide 12 reacts
with ortho-, meta- and para-aminobenzamides [amino-
benzamide : 12 : NiCl2·6H2O = 10 : 10 : 2, 70°С,
EtOH, 24 h] with the formation of the products 1, 3
and 5 with yields of 30, 31 and 38%, respectively. The
reaction of aminobenzamides with N,N'-bis[(dime-
thylamino)methyl]allophanamide (aminobenzamide :
13 : NiCl2·6H2O = 10 : 10 : 2, 70°C, EtOH, 24 h) takes
place with the formation of compounds 7 (14%), 8
(20%) and 9 (22%, Scheme 6). In the case of N-({[(di-
methylamino)methyl][(2-methylenehydrazino)carbo-
nyl]amino}methyl)-N,N-dimethylamine 14, the
It can be assumed [11, 12] that the amino-
methylation reaction of aminobenzamides with use of
bis(N,N-dimethylamino)methane and carbamides goes
through a stage of intermediate formation of amino-
methylated carbamide derivatives, which then react
with aminobenzamides to form the target products. To
verify this assumption, we synthesized N,N'-bis(di-
methylaminomethyl)urea 12, N,N'-bis [(dimethyl-
amino)methyl]allophanamide 13 and N-({[(dimethyl-
amino)methyl][(2-methylenehydrazino)carbonyl]amino}-
Scheme 5.
X
X
X
NH2
NMe2
NMe2
X = C=O (12), O=CNHC=O (13), C(O)NH (14).
H2N
NH
NMe2
HN
Me2N
N
[kat]
N
[kat]
Me2N
Me2N
+
CH2
Me2N
−Me2NH
−Me2NH
12, 13
14
NMe2
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CATALYTIC AMINOMETHYLATION OF AMINOBENZAMIDES
207
Scheme 6.
O
O
H2N
H2N
O
NH2
12 or 13, [Ni]
−Me2NH
14, [Ni]
HN
HN
−Me2NH
H
Me2N
N
NH
N
NMe2
N
NH2
X
X
H2C
1, 3, 5, 9
10, 11
X = C=O (1, 3, 5), O=CNHC=O (7−9), C(O)NH (11).
reaction with meta- and para-aminobenzamides under
similar conditions [aminobenzamide : 14 : NiCl2·6H2O =
10 : 10 : 2, 70°C, EtOH, 24 h] leads to the formation of
compounds 10 (15%) and 11 (11%); ortho-amino-
benzamide did not react.
aromatic ring HCC(NH2)C and the urea carbonyl
group.
In the IR spectra of compounds 3, 5, 7, 9‒11, there
are broadened absorption bands in the region of 1694–
1689 cm–1 corresponding to the stretching vibrations of
the carbonyl groups (amide I band) and at 1567–
1515 cm–1 (amide II band) due to the bending
vibrations of the C–N group.
Structure of compounds 1, 3, 5, 7–14 was
confirmed by NMR (1D, 2D), IR spectroscopy and
mass spectrometry data. According to HSQC data, in
1
the 13C and H NMR spectra of 1, 3 and 5, the signals
The results obtained suggest [7, 26, 27] that, under
the reaction conditions, aminomethylation of carba-
mides with bis(N,N-dimethylamino)methane initially
occurs with the formation of the corresponding
aminomethylated carbamides 12–14 [11, 12], which
are coordinated with the catalyst metal ion, which
contributes to the shift of the electron density from the
nitrogen atom to the metal ion and the formation of
carbocations. Subsequent nucleophilic addition of the
amino group of amino benzamides to the formed
carbocation leads to the formation of the
corresponding C–N bonds and acyclic molecules of 1,
3, 5, 7–11 (Scheme 7).
at δC ~61 ppm (δH ~3.9‒4.3 ppm) and δC ~48 ppm (δH
~4.5 ppm) refer to the Me2NCH2NH and HNCH2NH
fragments, respectively. A reliable confirmation of this
signal assignment is the data of HMBC heteronuclear
correlation experiment. A low-field signal at δH
~ 4.5 ppm interacts with the signal of the carbon atom
of the aromatic ring HCC(NH2)C and urea carbonyl
group, while a stronger field signal at δH ~ 3.9‒
4.3 ppm correlates with the signals of urea carbonyl
group and Me2N fragment. Analysis of COSY spectral
data showed that the hydrogen atoms of the methylene
group (δH ~4.5 ppm) interact with the vicinal NH
protons (δH ~6.3–7.6 ppm), and the methylene protons
(δH ~3.9–4.3 ppm) correlate with the NH hydrogen
atom (~7.8‒8.3 ppm), which indicates its relatively
greater acidity.
In summary, the aminomethylation reaction of
ortho-, meta- and para-aminobenzamides using bis-
(N,N-dimethylamino)methane and carbamides or N-
aminomethylated carbamides in the presence of
NiCl2·6H2O and SmCl3·6H2O as catalysts can be
successfully used for obtain acyclic aniline derivatives
bearing urea fragments.
The obtained results were used to identify reaction
1
products with biuret 7–9. In the H NMR spectra of
aminomethylated products 10 and 11, doublets in the
2
region of δH 6.0‒7.0 ppm with J = 12.0 Hz indicate
the presence of a terminal double bond in the
molecule. We observed a similar spectral spin system
in the case of N-({[(dimethylamino)methyl][(2-me-
thylenehydrazino)carbonyl]amino}methyl)-N,N-dimethyl-
amine 14. According to HMBC data, the double bond
protons are removed, and the methylene protons at
δH ~4.2 and 4.5 ppm of the Me2NCH2N and HNCH2N
fragments interact with the carbon atoms of the
EXPERIMENTAL
One-dimensional (1H, 13C), homo- (COZY) and
heteronuclear (HSQC, HMBC) NMR experiments
were performed on a Bruker Avance 400 [100.62 (13C)
and 400.13 MHz (1H)] spectrometer using DMSO-d6
as the solvent. Mass spectra were recorded on a
MALDI TOF/TOF AUTOFLEX III Bruker
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 2 2019

208
KHAIRULLINA et al.
Scheme 7.
X
R1 NH2
+
kat
Me
Me
N
N
R2
N
X
X
R1
Me Me
HN
..
+
Me
Me
R1
N
N
O
R2 kat
NH2
12−14
O
NH2
X
H
+
NH2
R1 N CH2
N
−kat
−Me2NH
R2
Me
..
O
H
N kat
NH2
Me
R1 = N(H)CH2NMe2, R2 = H (a); R1 = N(H)C(O)N(H)CH2NMe2, R2 = H (b); R1 = N(H)N=CH2, R2 = CH2NMe2 (c).
instrument. IR spectra were taken on a Bruker Vertex
70 V spectrometer from a suspension in liquid paraffin.
Melting points were determined on a PHMK 80/2617
instrument. The reaction progress was monitored by
TLC using Sorbfil plates (PTSH-AF-B) and detecting
with iodine vapors. KSK silica gel (100–200 µm) was
used for column chromatography.
br. s (6Н, NСH3), 4.25 br. s (2Н, MeNСH2NH), 4.52 t
3
3
(2Н, HNСH2NH, J = 5.5 Hz), 6.45 t (1Н, HCAr, J =
3
7.6 Hz), 6.65 d (1Н, HCAr, J = 8.0 Hz), 7.07 t (1Н,
3
3
HCAr, J = 7.5 Hz), 7.49 d (1Н, HCAr, J = 8.0 Hz);
6.71 br. s, 7.40 br. s and 8.34 br. s (3Н, NH). 13С NMR
spectrum, δС, ppm: 40.50 (NСH3), 48.33 (HNСH2NH),
61.71 (HNСH2NMe), 114.10 (Ph), 114.99 (Ph), 116.89
(Ph), 129.12 (Ph), 132.25 (Ph), 148.64 (Ph), 159.28
(С=O), 172.08 [С(O)NH2]. Mass spectrum, m/z (Irel,
%): 266.176 [М + H]+, 288.154 [М + Na]+, 304.130
[М + K]+.
Synthesis of compounds 1‒11 (general proce-
dure). a. A mixture of 1 mmol of carbamide in 5 mL of
ethanol, 2.5 mmol of bis(N,N-dimethylamino)methane
and 0.2 mmol of catalyst NiCl2·6H2O or SmCl3·6H2O
was stirred for 5 min, then solution of 1 mmol of
aminobenzamide in 5 mL of ethanol was added. The
temperature was raised to 80°C, and the reaction
mixture was stirred for 12 h. The target products were
isolated by column chromatography on SiO2.
2-Amino-N-[(dimethylamino)methyl]benzamide
(2). Yield 0.06 g (30%, method a), cream amorphous
powder, mp 40‒46°C. IR spectrum, ν, cm–1: 3438,
2923‒2854, 1654, 1607, 1585, 1461, 1305, 1281,
1152, 1035, 722. 1Н NMR spectrum, δ, ppm: 2.25 br. s
(6Н, NСH3), 4.06 br. s (2Н, MeNСH2NH), 6.40 br. s
(2Н, NH2), 6.54 t (1Н, HCAr, 3J = 7.4 Hz), 6.86 d (1Н,
b. A mixture of 1 mmol of N,N'-bis(dimethyl-
aminomethyl)urea, N,N'-bis[(dimethylamino)methyl])-
allophanamide or N-({[(dimethylamino)methyl][(2-me-
thylenehydrazino)carbonyl]amino}methyl)-N,N-dimethyl-
amine in 5 mL of ethanol and 0.2 mmol of catalyst
NiCl2·6H2O or SmCl3·6H2O was stirred for 5 min,
then 1 mmol of aminobenzamide in 5 mL of ethanol
was added, and the mixture was stirred for 24 h at 80°C.
The target products were isolated by column chromato-
graphy on SiO2.
3
3
HCAr, J = 8.3 Hz), 7.21 t (1Н, HCAr, J = 8.3 Hz),
3
7.56 d (1Н, HCAr, J = 7.4 Hz), 8.23 br. s (1Н, NH).
13С NMR spectrum, δС, ppm: 41.77 (NСH3), 61.07
(HNСH2NMe), 112.25 (Ph), 115.10 (Ph), 115.31 (Ph),
129.49 (Ph), 132.76 (Ph), 150.36 (Ph), 170.18
[С(O)NH2]. Mass spectrum, m/z (Irel, %): 232.110
[М + K]+.
3-({[({[(Dimethylamino)methyl]amino}carbonyl)-
amino]methyl}amino)benzamide (3). Yield 0.17 g
(64%, method a), 0.09 g (31%, method b), cream
amorphous powder, mp 65–70°С. IR spectrum, ν, cm–1:
3402, 2923–2854, 2724, 1654 br, 1607, 1581, 1460,
2-({[({[(Dimethylamino)methyl]amino}carbonyl)-
amino]methyl}amino)benzamide (1). Yield 0.18 g
(67%, method a), 0.08 g (30%, method b), cream
gummy substance. IR spectrum, ν, cm–1: 3401‒3334,
2965, 2781, 1667, 1615, 1556, 1468, 1395, 1263,
1159, 1022, 756, 630. 1Н NMR spectrum, δ, ppm: 2.54
1
1377, 1168, 1152, 1030, 973, 722. Н NMR spectrum,
δ, ppm: 2.19 br. s (6Н, NСH3), 4.04 br. s (2Н,
MeNСH2NH), 4.46 br. s (2Н, HNСH2NH), 5.64 br. s
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CATALYTIC AMINOMETHYLATION OF AMINOBENZAMIDES
209
(2Н, NH2), 6.82, 7.07‒7.16 m (4Н, HCAr); 6.28 br. s,
6.70 br. s and 8.50 br. s (3Н, NH). 13С NMR spectrum,
δС, ppm: 41.46 (NСH3), 48.78 (HNСH2NH), 62.27
(HNСH2NMe), 111.82 (Ph), 115.97 (Ph), 116.99 (Ph),
129.15 (Ph), 135.54 (Ph), 147.69 (Ph), 159.02 (С=O),
169.13 [С(O)NH2]. Mass spectrum, m/z (Irel, %):
266.074 [М + H]+, 288.061 [М + Na]+, 304.007
[М + K]+.
IR spectrum, ν, cm–1: 3327, 2946, 2867–2782, 1694 br,
1640 br, 1567‒1519, 1455, 1384, 1260, 1162, 1032,
1
752, 632. Н NMR spectrum, δ, ppm: 2.18 br. s (6Н,
3
NСH3), 3.98 d (2Н, MeNСH2NH, J = 6.1 Hz), 4.66
br. s (2Н, HNСH2NH); 6.52 m, 6.69 m, 7.14 m and
7.53 m (4Н, HCAr); 7.95 br. s, 8.02 br. s, 8.13 br. s and
8.56 br. s (4Н, NH). 13С NMR spectrum, δС, ppm:
41.77 (NСH3), 48.00 (HNСH2NH), 61.73
(HNСH2NMe), 114.10 (Ph), 115.05 (Ph), 116.84 (Ph),
128.70 (Ph), 132.40 (Ph), 148.40 (Ph), 155.47 (С=O),
155.94 (С=O), 171.79 [С(O)NH2]. Mass spectrum, m/z
(Irel, %): 307.328 [М + H]+.
3-Amino-N-[(dimethylamino)methyl]benzamide
(4). Yield 0.03 g (16%, method a), cream amorphous
powder, mp 86‒89°C. IR spectrum, ν, cm–1: 3332,
2925‒2854, 1651, 1606, 1584, 1455, 1304, 1280, 1154,
1
1030, 722. Н NMR spectrum, δ, ppm: 2.20 br. s (6Н,
3-[(8-Methyl-3,5-dioxo-2,4,6,8-tetraazanon-1-yl)-
amino]benzamide (8). Yield 0.12 g (40%, method a),
0.06 g (20%, method b), creamy gummy substance. IR
spectrum, ν, cm–1: 3337, 2948, 2854–2782, 1689 br,
1652 br, 1539, 1464, 1383, 1255, 1139, 1032, 753,
NСH3), 3.86 br. s (2Н, MeNСH2NH), 6.98‒7.15 m (4Н,
HCAr), 6.60 br. s (1Н, NH). 13С NMR spectrum, δС,
ppm: 42.47 (NСH3), 61.58 (HNСH2NMe), 113.36
(Ph), 113.55 (Ph), 115.16 (Ph), 129.02 (Ph), 136.84
(Ph), 149.11 (Ph), 168.24 [С(O)NH2]. Mass spectrum,
m/z (Irel, %): 232.097 [М + K]+.
1
692. Н NMR spectrum, δ, ppm: 2.14 br. s (6Н,
NСH3), 3.95 br. s (2Н, MeNСH2NH), 4.55 br. s (2Н,
NСH2NH); 6.84‒6.85 m, 7.06‒7.10 m and 7.11‒7.17
m (4Н, HCAr); 6.57 br. s, 6.64 br. s, 7.95 and 8.85 br. s
(4Н, NH), 8.73 br. s (2Н, NH2). 13С NMR spectrum,
δС, ppm: 41.86 (NСH3), 52.40 (HNСH2NH), 61.84
(HNСH2NMe), 111.62 (Ph), 115.73 (Ph), 116.07 (Ph),
129.15 (Ph), 135.82 (Ph), 147.91 (Ph), 155.48 (С=O),
155.93 (С=O), 169.00 [С(O)NH2]. Mass spectrum, m/z
(Irel, %): 307.353 [М + H]+.
4-({[({[(Dimethylamino)methyl]amino}carbonyl)-
amino]methyl}amino)benzamide (5). Yield 0.19 g
(70%, method a), 0.10 g (38%, method b), cream
amorphous powder, mp 124–126°C. IR spectrum, ν,
cm–1: 3438‒3353, 2921, 2870–2730, 1666 br, 1614 br,
1
1555, 1454, 1351, 1215, 1142, 1039, 757, 668. Н
NMR spectrum, δ, ppm: 2.27 br. s (6Н, NСH3), 3.94
3
br. s (2Н, MeNСH2NH), 4.45 t (2Н, HNСH2NH, J =
3
6.0 Hz), 5.67 br. s (2Н, NH2), 6.68 d (2Н, HCAr, J =
4-[(8-Methyl-3,5-dioxo-2,4,6,8-tetraazanon-1-yl)-
amino]benzamide (9). Yield 0.16 g (51%, method a),
0.07 g (22%, method b), cream amorphous powder, mp
>350°C. IR spectrum, ν, cm–1: 3306, 2923, 2854, 1694
br, 1605 br, 1515, 1462, 1377, 1261, 1189, 1030, 841,
8.6 Hz), 7.66 d (2Н, HCAr, 3J = 8.6 Hz), 6.86 br. s and
6.94 br. s (3Н, NH). 13С NMR spectrum, δС, ppm:
41.90 (NСH3), 48.48 (HNСH2NH), 62.11
(HNСH2NMe), 113.00 (Ph), 121.80 (Ph), 129.35 (Ph),
150.50 (Ph), 159.13 (С=O), 168.80 [С(O)NH2]. Mass
spectrum, m/z (Irel, %): 266.063 [М + H]+, 287.250
[М + Na ‒ H]+.
1
768. Н NMR spectrum, δ, ppm: 2.13 br. s (6Н,
NСH3), 4.01 (2Н, MeNСH2NH), 4.61 br. s (2Н,
HNСH2NH), 6.79 br. s (2Н, NH2), 6.67‒6.73 m (2Н,
HCAr), 7.65‒7.70 m (2Н, HCAr); 6.82 br. s, 6.78 br. s,
6.94 br. s and 8.43 br. s (4Н, NH). 13С NMR spectrum,
δС, ppm: 41.93 (NСH3), 48.03 (HNСH2NH), 61.79
(HNСH2NMe), 111.86 (Ph), 121.98 (Ph), 129.37 (Ph),
150.15 (Ph), 154.89 (С=O), 155.43 (С=O), 168.38
[С(O)NH2]. Mass spectrum, m/z (Irel, %): 307.378
[М + H]+.
4-Amino-N-[(dimethylamino)methyl]benzamide
(6). Yield 0.03 g (18%, method a), cream amorphous
powder, mp 85‒90°C. IR spectrum, ν, cm–1: 3400,
2923‒2854, 1657, 1606, 1584, 1462, 1304, 1283,
1153, 1031, 722. 1Н NMR spectrum, δ, ppm: 2.21 br. s
(6Н, NСH3), 4.05 br. s (2Н, MeNСH2NH), 6.54 d (2Н,
3
3
HCAr, J = 8.6 Hz), 7.59 d (2Н, HCAr, J = 8.6 Hz),
8.57 br. s (1Н, NH). 13С NMR spectrum, δС, ppm:
42.93 (NСH3), 61.50 (HNСH2NMe), 112.15 (Ph),
121.02 (Ph), 129.38 (Ph), 152.28 (Ph), 167.69 [С(O)
NH2]. Mass spectrum, m/z (Irel, %): 194.281 [М + H]+.
3-[({[(Dimethylamino)methyl][(2-methylenehyd-
razino)carbonyl]amino}methyl]amino]benzamide
(10). Yield 0.12 g (40%, method a), 0.04 g (15%,
method b), creamy gummy substance. IR spectrum, ν,
cm–1: 3401, 2860‒2786, 1666, 1606, 1538, 1468, 1385,
2-[(8-Methyl-3,5-dioxo-2,4,6,8-tetraazanon-1-yl)-
amino]benzamide (7). Yield 0.13 g (43%, method a),
0.04 g (14%, method b), colorless gummy substance.
1
1285, 1121, 1022, 759, 622. Н NMR spectrum, δ,
ppm: 2.40 br. s (6Н, NСH3), 4.18 br. s (2Н,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 2 2019

210
KHAIRULLINA et al.
MeNСH2NH), 4.54 t (2Н, NСH2NH, 3J = 5.9 Hz), 6.18
d and 6.82 d (2Н, N=СH2, J = 12.0 Hz); 6.69 m and
(14). Yield 0.32 g (80%), colorless gummy substance.
IR spectrum, ν, cm–1: 3439, 2785, 1668, 1581‒1536,
1469, 1384, 1335, 1143, 1022, 923, 612. Н NMR
2
1
7.03‒7.20 m (4Н, HСAr),7.38 br. s and 8.80 br. s (2Н,
NH). 13С NMR spectrum, δС, ppm: 40.89 (NСH3),
52.26 (NСH2NH), 61.43 (HNСH2NMe), 113.35 (Ph),
115.07 (Ph), 117.11 (Ph), 129.25 (Ph), 131.26
(N=СH2), 135.11 (Ph), 147.83 (Ph), 156.10 (С=O),
168.65 [С(O)NH2]. Mass spectrum, m/z (Irel, %):
293.135 [М + H]+, 331.081 [М + K].
spectrum, δ, ppm: 2.54 br. s (6Н, NСH3), 4.32 d (2Н,
3
HNСH2NH, J = 6.9 Hz), 6.32 d and 6.93 d (2Н,
2
3
СH2=N, J = 12.0 Hz), 7.82 t [1Н, CH2NHC(O), J =
6.9 Hz], 10.81 br. s [1Н, NNHC(O)]. 13С NMR
spectrum, δС, ppm: 41.00 (NCH3), 61.12 (HNСH2NH),
133.70 (СH2=N), 155.87 (С=O). Mass spectrum, m/z
(Irel, %): 143.037 [М ‒ H]+, 145.049 [М + H]+, 167.079
[М + Na]+.
4-[({[(Dimethylamino)methyl][(2-methylenehyd-
razino)carbonyl]amino}methyl)amino]benzamide
(11). Yield 0.08 g (29%, method a), 0.03 g (11%,
method b), creamy gummy substance. IR spectrum, ν,
cm–1: 3443, 2852–2796, 1659 br, 1608, 1529, 1469,
FUNDING
This work was performed in accordance with the
research plan of the Institute of Petrochemistry and
Catalysis of the Russian Academy of Sciences on the
topic “Metal complex catalysis in the synthesis of
hetero- and metal heterocycles” (state registration
number AAAA-A17-117012610060-7, 2017–2019)
using equipment of the Center for collective use
“Agidel.”
1
1395, 1273, 1193, 1108, 1021, 843, 593. Н NMR
spectrum, δ, ppm: 2.45 br. s (6Н, NСH3), 4.24 br. s
(2Н, MeNСH2NH), 4.55 br. s (2Н, NСH2NH), 6.31 d
2
and 6.89 d (2Н, N=СH2, J = 12.1 Hz), 6.52 d (2Н,
3
3
HСAr, J = 8.5 Hz), 6.89 d (2Н, HСAr, J = 8.5 Hz),
6.96 br. s and 8.96 br. s (2Н, NH). 13С NMR spectrum,
δС, ppm: 41.13 (NСH3), 51.80 (NСH2NH), 65.35
(HNСH2NMe), 111.76 and 129.47 (Ph), 131.13
(N=СH2), 132.87 (Ph), 150.58 (Ph), 156.03 (С=O),
168.72 [С(O)NH2]. Mass spectrum, m/z (Irel, %):
293.142 [М + H]+.
CONFLICT OF INTEREST
No conflict of interest was declared by the authors.
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