Catalytic Cycloaminomethylation of Aminobenzamides with 1,3-Bis[dimethylamino(methoxy)methyl]thiourea

Article abstract of DOI:10.1134/S1070363219030022

Efficient methods of the synthesis of cyclophanes containing the thiourea moiety via the reaction of o-, m-, and p-aminobenzamides with 1,3-bis(dimethylaminomethyl)thiourea or 1,3-bis(methoxymethyl)thiourea using NiCl₂·6H₂O and SmCl₃·6H₂O as catalysts have been developed.

Full text of DOI:10.1134/S1070363219030022

ISSN 1070-3632, Russian Journal of General Chemistry, 2019, Vol. 89, No. 3, pp. 378–384. © Pleiades Publishing, Ltd., 2019.
Russian Text © R.R. Khairullina, Т.V. Tyumkina, А.R. Geniyatova, М.F. Abdullin, А.G. Ibragimov, 2019, published in Zhurnal Obshchei Khimii, 2019,
Vol. 89, No. 3, pp. 342–349.
Catalytic Cycloaminomethylation of Aminobenzamides
with 1,3-Bis[dimethylamino(methoxy)methyl]thiourea
a
a
a
R. R. Khairullina *, Т. V. Tyumkina , А. R. Geniyatova ,
b
a
М. F. Abdullin , and А. G. Ibragimov
a
Institute of Petrochemistry and Catalysis of the Russian Academy of Sciences,
pr. Oktyabrya 141, Ufa, 450075 Russia
*
е-mail: ink@anrb.ru
b
Ufa Institute of Chemistry of the Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Russia
Received October 18, 2018; revised October 18, 2018; accepted October 25, 2018
Abstract—Efficient methods of the synthesis of cyclophanes containing the thiourea moiety via the reaction of
о-, m-, and p-aminobenzamides with 1,3-bis(dimethylaminomethyl)thiourea or 1,3-bis(methoxymethyl)thiourea
using NiCl ·6H O and SmCl ·6H O as catalysts have been developed.
2 2 3 2
Keywords: cycloaminomethylation; aminobenzamides; bis(N,N-dimethylamino)methane; thiourea; cyclophanes
DOI: 10.1134/S1070363219030022
Classical method for the synthesis of cyclic amino-
methylated carboxamides consists in the condensation
of carboxamides with formaldehyde and NH-acids [1‒6].
The two-component condensation of amines with 1,3-
di(methylol)urea or 1,3-di(methylol)thiourea is an
efficient method of preparation of aminomethylated
carboxamides [6, 7].
bis(dimethylaminomethyl)thiourea and 1,3-bis(methoxy-
methyl)thiourea with о-, m-, and p-aminobenzamides,
as well as aminomethylation of the latter with thiourea
and bis(N,N-dimethylamino)methane or paraform
catalyzed by the compounds of transition and rare-
earth metals.
Aminomethylating reagents, 1,3-bis(dimethylamino-
methyl)thiourea 1 [19] and 1,3-bis(methoxymethyl)-
thiourea 2, were obtained via the reaction of thiourea
with bis(N,N-dimethylamino)methane in ethanol or
with paraform in methanol, the reagents ratio being
thiourea : bis(N,N-dimethylamino)methane (para-
form) : SmCl ·6H O = 10 : 20 : 0.5, at 80°С, for
Cyclic thiocarbamides exhibit complex-forming [8]
and transfection properties [9], possess antioxidant
[10], antiviral, and antibacterial activity [5, 11]. Deri-
vatives of aminobenzamides display antitumor [12‒14]
and antibacterial activity [15] and are promising activa-
tors of enzyme glucokinase [16, 17] and luminescence
markers in biological systems [18].
3
2
8 h (Scheme 1).
Extending our studies on catalytic aminomethyla-
tion of carboxamides [19‒22] and on efficient ap-
proaches to the synthesis of cyclophanes containing a
thiocarbamide fragment, we studied the reaction of 1,3-
Using the reaction of cycloaminomethylation of о-
aminobenzamide with 1,3-bis(dimethylaminomethyl)-
thiourea 1 (aminobenzamide : 1 : [cat] = 10 : 10 : 2,
70°С, EtOH, 24 h) as an example, we found that,
Scheme 1.
S
NMe
2
S
S
,
[Sm]
(
CH O) ,
2 n
HN
Me N
NH
NMe2
HN
MeO
NH
OMe
NMe2
Me NH
MeOH, [Sm]
H N
NH
2
2
−
H O
−
2
2
2
1
2
3
78

CATALYTIC CYCLOAMINOMETHYLATION OF AMINOBENZAMIDES
379
Scheme 2.
S
H
S
O
N
NH
NH
NH
NH2
[
Sm]
HN
HN
O
+
X
X
NH2
1
, 2
3−5
X = NMe (1), OMe (2); ortho- (3), meta- (4), para- (5).
2
unlike the case of 1,3-bis(dimethylaminomethyl)urea
22], the reaction proceeded with the formation of 4-
thioxo-2,3,4,5,6,7-hexahydro-1,3,5,7-benzotetraazecin-
component condensation of bis(N,N-dimethylamino)
methane, (thio)urea, and NH-acids [19, 20]. In
continuation of earlier studies of aminomethylation of
ureas [21, 22], we studied the reaction of
aminobenzamides cycloaminomethylation with bis
(N,N-dimethylamino)methane (paraform) and thiourea
in the presence of the catalysts, which had
demonstrated the highest activity.
[
8
3
(1H)-one 3 in 40 (NiCl ·6H O), 36 (SmCl ·6H O),
2 2 3 2
0 [Sm(NO ) ·6H O], and 29% [Ni(NO ) ·6H O]
3
3
2
3 2
2
yield (Scheme 2). Cycloaminomethylation of о-amino-
benzamide with 1,3-bis(methoxymethyl)thiourea 2
gave compound 3 in 37 (SmCl ·6H O), 30 [Sm(NO ) ·
3
2
3 3
6
H O], 15 (NiCl ·6H O), and 12 % [Ni(NO ) ·6H O]
2 2 2 3 2 2
The aminomethylation of о-, m-, and p-amino-
benzamides with bis(N,N-dimethylamino)methane and
yield (Scheme 2). The reaction did not occur in the
absence of a catalyst.
thiourea at the aminobenzamide
:
bis(N,N-di-
Cycloaminomethylation of m- and p-amino-
benzamides with the aminomethylating reagents 1 and
methylamino)methane : thiourea : NiCl ·6H O ratio of
2
2
10 : 20 : 10 : 2 (70°С, EtOH, 24 h) resulted in the
formation of compounds 3‒5 in 45, 50, and 40% yield,
respectively (Scheme 3). Under the conditions of the
reaction of aminomethylation of thiourea, as in the
case of urea [22], 2-(3-,4-)-amino-N-[(dimethylamino)-
methyl]benzamides 6‒8 were formed in the yield not
exceeding 15%. No aminomethylation reaction
occurred in the absence of catalyst.
2
under similar conditions [aminobenzamide : 1(2) :
NiCl ·6H O (SmCl ·6H O) = 10 : 10 : 2, 70°С, EtOH,
2
2
3
2
2
4
h] led the formation of 5-thioxo-2,4,6,8-
tetraazabicyclo[8.3.1]tetradeca-1(14),10,12-trien-9-one
4
and 5-thioxo-2,4,6,8-tetraazabicyclo[8.2.2]tetradeca-
1
(12),10,13-trien-9-one 5 in 40 (42%) and 39 (40%)
yield, respectively (Scheme 2).
One of the methods for the synthesis of the
heterocycles containing thiourea fragments is the three-
The chemoselectivity of the three-component
reaction was found dependent on the order of the
Scheme 3.
O
S
H
N
O
NH2
NH
NH
NH2
+
HN
O
[
Sm]
NH
NMe2
+
NH2
Me N
NMe2
2
+
S
H N
NH2
3−5
6−8
2
ortho- (3, 6), meta- (4, 7), para- (5, 8).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 3 2019

3
80
KHAIRULLINA et al.
Scheme 4.
S
H
N
O
NH
NH
HN
HN
NH2
O
[
Sm]
HN
O
+
+
(CH O)
2 n
NH2
NH2
NH2
O
+
H N
NH2
3
9
2
S
reagents mixing. For example, successive mixing of о-
aminobenzamide with paraform and then with thiourea
led to the formation of 2-({[2-(aminocarbonyl)phenyl]-
amino}methylamino)benzamide 9 in ~70% yield, and
the product did not further react with thiourea (Scheme 4).
However, successive mixing of paraform with thiourea
and then with о-aminobenzamide under the same
conditions (paraform:thiourea : aminobenzamide :
SmCl ·6H O = 20 : 10 : 10 : 2, 70°С, MeOH, 24 h)
compounds 3‒5 contained the peaks of molecular ions
+
of associates [М + H O ‒ H] 253.203 (3), 253.221 (4),
2
and 253.260 (5), respectively. Positive-ion chemical
ionization mass spectra at atmospheric pressure
(APCI) of compounds 3‒5 showed the peaks of
+
characteristic ions [M‒C H N S+H] with m/z 149
2
4
2
+
(Scheme 6) and weaker peaks [M ‒ C H N + H] with
2
3
2
m/z 164. In the case of compounds 4, 5, weak peaks of
+
molecular ions [М + H] with m/z 237 and the peaks of
3
2
yielded bicyclic compound 3 in 60% yield (Scheme 4).
ions of associates with the solvent [M ‒ C H N S +
2 4 2
+
CH OH + H] with m/z 181 were registered, their
3
Aminomethylation of m- and p-aminobenzamides
with paraform and thiourea [paraform : thiourea :
aminobenzamide : SmCl ·6H O = 20 : 10 : 10 : 2, 70°С,
intensity in the spectrum of compound 5 being the
highest. Besides, the negative-ion APCI mass spectra
of compounds 3‒5 contained the peaks of molecular
3
2
MeOH, 24 h] gave cyclophanes 4 and 5 in 59 and 43%
yield, respectively. Under those conditions, the
formation of sym-1,3,5-triazinanes 10 and 11 was
observed in the yields not exceeding 20% (Scheme 5).
–
ions [M ‒ H] with m/z 235.
1
13
Broadened signals in the H and C NMR spectra
of compounds 3‒5 at δ ~ 66 and 52 ppm were
С
The structure of compounds 3‒5 was determined by
means of NMR and IR spectroscopy as well as mass
spectrometry. MALDI TOF/TOF spectra of
assigned to carbon atom of the NCH N bond of the
heterocycle. That broadening was apparently caused
by slow (in the NMR timescale) conformational
2
Scheme 5.
O
S
H
N
NH2
NH
NH
O
[
Sm]
N
+
(CH O)n
HN
O
+
2
H N
O
N
2
NH2
N
NH2
H N
2
+
H N
NH2
2
O
4, 5
10, 11
S
meta- (4, 10), para- (5, 11).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 3 2019

CATALYTIC CYCLOAMINOMETHYLATION OF AMINOBENZAMIDES
381
Scheme 6.
[1, 24, 25]. Subsequent nucleophilic addition of the
amino group to the formed carbocation led to the
formation of new C–N bonds and assembling of the
target heterocycles 3‒5 according to Scheme 7.
C H NS
2
3
72.9986 Da
C H N S
2
4
2
H
N
S
8
8.0095 Da
HN
In summary, the catalytic method for the synthesis
of cyclophanes containing the thiourea motif via the
reaction of cycloaminomethylation of о-, m- and p-
aminobenzamides with 1,3-bis(dimethylaminomethyl)-
thiourea and 1,3-bis(methoxymethyl)thiourea as well
as with thiourea, bis(N,N-dimethylamino)methane, and
paraform was developed.
NH
O
C H N O
8
8 2
148.0637 Da
N
H
C H N O
63.0746 Da
8
9 3
1
EXPERIMENTAL
transformations in the solution, similar to those
discussed for the conformational analysis of
macroheterocycle of 1,7-dithia-3,5-diazonan-4-thione
with flattened N(C=S)N fragment [23].
1
13
One-dimensional ( Н and С), homo- (COSY) and
heteronuclear (HSQC and HMBC) NMR experiments
were performed using
a
Bruker Avance 400
spectrometer (100.62 and 400.13 MHz, respectively;
The IR spectra of compounds 3‒5 contained
broadened absorption bands in the range of 1663‒
solvent: DMSO-d ). Mass spectra of compounds 1‒11
6
–
1
were recorded using
a
MALDI TOF/TOF
1
648 cm , corresponding to stretching of the (thio)
–
1
AUTOFLEX III Bruker instrument. The sample
preparation for registration of the mass spectra was
performed using the “dry drop” method. Mass spectra
of compounds 1, 3, 5 were also obtained using an
LCMS-2010 EV quadruple liquid chromato–mass
spectrometer (Shimadzu) in the chemical ionization
mode at atmospheric pressure (APCI), registering
positive or negative ions with capillary potential
4.5 kV and –3.5 kV, respectively. IR spectra were
recorded using a Bruker Vertex 70 v spectrometer
carbonyl groups (Amide I band) and 1580‒1505 cm
(
Amide II band) from deformational vibrations of the
C–N bond.
Under the conditions of the cycloaminomethylation
of о-, m- or p-aminobenzamides with thiourea and bis-
(
N,N-dimethylamino)methane or paraform, first,
apparently, 1,3-bis(dimethylaminomethyl)thiourea [19,
0] or 1,3-bis(methoxy)thiourea was formed, which
was coordinated at the central atom ion of the catalyst
2
Scheme 7.
Me
Me
NH2
N
N
S
Me Me
+
O
S
O
NH2
.
.
+
H
N
H
HN
N
X
+
N CH
H
S
[cat]
H
NH
2
HN
2
cat
X
H N
NH2
X
..
2
X cat
+
n
X = NMe , OMe
2
(
CH O) + MeOH
2
−
XH
S
H
N
S
S
.
.
NH
NH
+
H N
NH
X
N
NH
HN
O
H
−
[cat]
CH
cat
2
H
+
NH
NH
−XH
N
H N
2
.
.
H
X cat
O
O
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 3 2019

3
82
KHAIRULLINA et al.
(
suspension in Vaseline oil). Melting points were
а), 0.06 g (37%, method b), 0.08 g (45%, method c),
0.10 g (60%, method d); cream colored amorphous
powder, mp 44‒48°С. IR spectrum, cm : 3314, 2969‒
determined using a RNMK 80/2617 device. The
reaction was monitored by TLC method on Sorbfil
plates (PTCKh-AF-V) developed by iodine vapors.
The KSK silica (100‒200 μm) was used for column
chromatography.
–
1
2850, 1648, 1610, 1580, 1492, 1380, 1259‒1240,
1
1155, 1022, 756, 630. Н NMR spectrum (DMSO-d ),
6
δ, ppm: 4.65 br. s (2Н, HNСH NH), 4.72 br. s (2Н,
2
HNСH NH), 6.68 m (1Н, HC ), 6.92 t (1Н, HC ,
2
Ar
3
Ar
Aminomethylation (methoxymethylation) of
thiourea with bis(N,N-dimethylamino)methane
paraform). 25 mmol of bis(N,N-dimethylamino)-
methane (paraform) dissolved in 10 mL of ethanol
methanol) and 0.5 mmol SmCl ·6H O were stirred for
3 2
min. Then, 10 mmol of thiourea dissolved in the
3
J = 7.5 Hz), 7.28 t (1Н, HC , J = 7.5 Hz), 7.56 m
Ar
13
(
1Н, HC ), 8.08, 8.56 and 8.90 br. s (4Н, NH).
С
Ar
(
NMR spectrum, (DMSO-d6), δ, ppm: 63.03
(
(
(
HNСH NH), 66.54 (HNСH NH), 112.52 (Ph), 116.05
Ph), 116.95 (Ph), 129.50 (Ph), 132.95 (Ph), 148.23
2 2
(
5
Ph), 170.38 [С(O)NH ], 183.21 (С=S). MALDI TOF/
2
mixture of solvents CHCl –EtOH (MeOH) = 1 : 1 was
3
TOF mass spectrum, m/z (I , %): 253.203 [М + H O ‒
rel
2
added, and the reaction mixture was stirred for 8 h at
0°С. Thiourea derivatives 1 and 2 were isolated from
the reaction mass by column chromatography on silica.
+
H] . Mass spectrum (APCI), m/z (I , %): 149 (100) [M
rel
4
+
+
‒
(
C H N S + H] , 164 (26) [M ‒ C H NS + H] ; 147
2 4 2 2 3
-
-
33) [M ‒ C H N S – H] , 235 (12) [M ‒ H] .
2 4 2
1
,3-[Bis(dimethylaminomethyl)thiourea (1) [19].
5
-Thioxo-2,4,6,8-tetraazabicyclo[8.3.1]tetradeca-
White amorphous substance, yield 99%, mp 76–80°С.
MALDI TOF/TOF mass spectrum, m/z (I , %):
29.374 [М + K] .
1
(14),10,12-trien-9-one (4). Yield 0.07 g (40%,
method а), 0.07 g (42%, method b), 0.09 g (50%,
method c), 0.10 g (59%, method d); cream colored
amorphous powder, mp 68‒72°С. IR spectrum, cm :
3468‒3448, 2956‒2871, 1663, 1618, 1550, 1458,
1384, 1195, 1142, 1076, 754, 690. Н NMR spectrum
(DMSO-d
br. s (2Н, HNСH
7.17 m (2Н, HCAr), 6.68 and 9.00 br. s (4Н, NH). С
NMR spectrum, (DMSO-d ), δ, ppm: 52.50
HNСH NH), 63.34 (HNСH NH), 111.53 (Ph), 112.12
rel
+
2
–
1
1
,3-[Bis(methoxymethyl)thiourea (2). Colorless
2
0
1
tarry substance, yield 95%, nD 1.5000. Н NMR
spectrum (DMSO-d ), δ, ppm: 3.18 br. s (6Н, OСH ),
.84 br. s (4Н, HNСH O), 8.34 br. s (2Н, NH).
NMR spectrum, (DMSO-d ), δ, ppm: 55.42 (OСH ),
5.80 (HNСH O), 184.96 (С=O). MALDI TOF/TOF,
1
6
3
1
3
4
С
6
), δ, ppm: 4.55 br. s (2Н, HNСH
2
NH), 4.69
2
NH), 6.85‒6.90 m (2Н, HCAr), 7.05‒
6
3
2
1
3
7
2
+
mass spectrum, m/z (I , %): 203.112 [М + K] .
6
rel
(
(
(
2
2
Aminomethylation of aminobenzamides. a. Mix-
ture of 10 mmol of 1,3-bis(dimethylaminomethyl)-
thiourea in 10 mL of EtOH, 2 mmol of NiCl ·6H O,
and 10 mmol of aminobenzamide was stirred for 24 h
at 80°С. The target products were isolated from the
reaction mixture by column chromatography.
Ph), 115.66 (Ph), 129.17 (Ph), 135.00 (Ph), 147.00
Ph), 168.00 [С(O)NH ], 183.32 (С=S). MALDI TOF/
2
2
2
TOF mass spectrum, m/z (I , %): 253.221 [М + H O ‒
rel
2
+
H] . Mass spectrum (APCI), m/z (I , %): 149 (100)
rel
+
[
M ‒ C H N S + H] , 181 (19) [M ‒C H N S +
2 4 2 2 4 2
+
+
CH OH + H] , 237 (9) [М + H] ; 147 (97) [M ‒
3
-
-
b. The reaction was performed similarly using 1,3-bis-
C
2
H
4
N
2
S ‒ H] , 235 (34) [M ‒ H] .
(
dimethylaminomethyl)thiourea, SmCl ·6H O, and MeOH.
3 2
5
-Thioxo-2,4,6,8-tetraazabicyclo[8.2.2]tetradeca-
c. Mixture of 10 mmol of thiourea, 10 mL of
1(12),10,13-trien-9-one (5). Yield 0.07 g (39%,
method а), 0.07 g (40%, method b), 0.07 g (40%,
method c), 0.07 g (43%, method d); cream colored
EtOH, and 20 mmol of bis(dimethyl-amino)methane
was stirred for 1 h at 40°С, then 2 mmol of
NiCl ·6H O and 10 mmol of aminobenzamide dis-
–
1
amorphous powder, mp 65‒70°С. IR spectrum, cm :
3305, 2924‒2854, 1656, 1606, 1505, 1462, 1377,
2
2
solved in 5 mL of EtOH was added. The obtained
mixture was stirred at 80°С for 12 h. The target
products were isolated from the reaction mixture by
column chromatography.
1
1260, 1136, 1059, 839, 768, 722. Н NMR spectrum
(DMSO-d
br. s (2Н, HNСH
.62 d (2Н, HC , J = 8.6 Hz), 6.97 and 8.01 br. s
), δ, ppm: 4.27 br. s (2Н, HNСH NH), 4.56
6
2
3
NH), 6.56 d (2Н, HCAr, J = 8.6 Hz),
Ar
2
3
7
(
d. The reaction was performed similarly using
13
4Н, NH). С NMR spectrum, (DMSO-d ), δ, ppm:
6
thiourea, paraform, SmCl ·6H O, and MeOH.
3
2
5
1.92 (HNСH NH), 66.76 (HNСH NH), 113.02 (Ph),
2 2
4
-Thioxo-2,3,4,5,6,7-hexahydro-1,3,5,7-benzo-
122.52 (Ph), 129.15 (Ph), 151.37 (Ph), 168.67
[С(O)NH ], 183.28 (С=S). MALDI TOF/TOF mass
tetraazecin-8(1H)-one (3). Yield 0.07 g (40%, method
2
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 3 2019

CATALYTIC CYCLOAMINOMETHYLATION OF AMINOBENZAMIDES
383
+
spectrum m/z (I , %): 253.260 [М + H O ‒ H] . Mass
1,3,5-[3-(Aminocarbonyl)phenyl]-1,3,5-triazinane
rel
2
spectrum (APCI), m/z (I , %): 181 (100) [M ‒
(10). Yield 0.02 g (20%, method d), white amorphous
substance, mp 86‒94°С. IR spectrum, cm : 3375‒
rel
+
+
–1
C H N S + CH OH + H] , 237 (5) [М + H] , 149 (22)
2
4
2
3
+
+
[
(
M ‒ C H N S + H] , 164 (8) [M ‒ C H NS + H] ; 235
17) [M ‒ H] .
3170, 2924‒2854, 1615, 1578, 1461, 1377, 1277,
2
4
2
-
2
3
1
1153, 1060, 742, 633. Н NMR spectrum (DMSO-d
),
6
δ, ppm: 5.01 br. s (6Н, HNСH NH), 7.07‒7.16 m (6Н,
2
2
-Amino-N-[(dimethylamino)methyl]benzamide
1
HCAr), 7.25 m (3Н, HCAr), 7.31 m (3Н, HCAr), 6.85 br.
(
6). [22]. Н NMR spectrum, (DMSO-d ), δ, ppm: 2.21
br. s (6Н, NСH ), 4.06 br. s (2Н, MeNСH NH), 6.41
br. s (2Н, NH ), 6.51 m (1Н, HC ), 6.60 m (1Н,
6
13
s (6Н, NH ). С NMR spectrum (DMSO-d ), δ, ppm:
2
6
3
2
6
7.42 (HNСH NH), 112.07 (Ph), 116.33 (Ph), 119.76
2
2
Ar
3
(Ph), 129.28 (Ph), 135.43 (Ph), 148.54 (Ph), 168.53
[С(O)NH ]. MALDI TOF/TOF mass spectrum, m/z
I , %): 467.227 [М + Na] , 483.186 [М + K] .
HC ), 7.11 t (1Н, HC , J = 8.3 Hz), 7.48 m (1Н,
Ar
Ar
1
3
2
HC ), 8.08 br. s (1Н, NH). С NMR spectrum,
Ar
+
+
(
rel
(
(
1
[
(
DMSO-d6), δ, ppm: 41.96 (NСH3), 60.98
HNСH NMe), 112.52 (Ph), 115.30 (Ph), 116.45 (Ph),
29.13 (Ph), 132.60 (Ph), 150.34 (Ph), 171.92
С(O)NH ]. MALDI TOF/TOF mass spectrum, m/z
2
1,3,5-[4-(Aminocarbonyl)phenyl]-1,3,5-triazinane
1
(11). Yield 5%, method b. Н NMR spectrum (DMSO-
d ), δ, ppm: 4.60 br. s (6Н, HNСH NH), 6.72 m (6Н,
2
6
2
+
13
I , %): 193.188 [М] .
rel
HCAr), 7.64 m (6Н, HCAr), 7.08 br. s (6Н, NH
NMR spectrum (DMSO-d6), δ, ppm: 68.25
(HNСH NH), 112.30 (Ph), 123.75 (Ph), 129.60 (Ph),
50.34 (Ph), 169.34 [С(O)NH ]. MALDI TOF/TOF
2
).
С
3
-Amino-N-[(dimethylamino)methyl]benzamide
1
2
(
2
6
7) ([22]). Н NMR spectrum (DMSO-d ), δ, ppm:
.27 br. s (6Н, NСH ), 4.11 br. s (2Н, MeNСH NH),
3 2
.89‒7.30 m (4Н, HC ), 6.43 br. s (1Н, NH).
6
1
2
+
1
3
mass spectrum, m/z (Irel, %): 467.437 [М + Na] .
С
Ar
NMR spectrum, (DMSO-d ), δ, ppm: 42.22 (NСH ),
6
3
FUNDING
6
1.46 (HNСH NMe), 113.36 (Ph), 114.97 (Ph), 115.66
2
(
[
(
Ph), 129.26 (Ph), 135.51 (Ph), 149.12 (Ph), 168.23
This work was performed as a part of Research
work of IPC RAS (no. 0246-2018-0048, 2018–2020),
UIC RAS (no. АААА-А17-117011910027-0, 2017–
С(O)NH ]. MALDI TOF/TOF mass spectrum, m/z
2
+
I , %): 192.941 [М] .
rel
2
019), and with financial support from the Federal
4
-Amino-N-[(dimethylamino)methyl]benzamide
Agency for Science and Innovations (Grant of the
President of Russian Federation NSh 5240.2018.3)
using the equipment of the Centers for Collective Use
1
(
8) ([22]). Н NMR spectrum (DMSO-d ), δ, ppm:
.21 br. s (6Н, NСH ), 4.06 br. s (2Н, MeNСH NH),
3 2
.71 d (2Н, HC , J = 8.5 Hz), 7.68 d (2Н, HC , J =
.5 Hz), 8.43 br. s (1Н, NH). С NMR spectrum
6
2
6
8
3
3
Ar
Ar
“Agidel” and “Chemistry.”
1
3
(
(
1
DMSO-d6), δ, ppm: 42.28 (NСH3), 61.50
CONFLICT OF INTEREST
HNСH NMe), 112.17 (Ph), 121.77 (Ph), 129.29 (Ph),
2
No conflict of interest was declared by authors.
REFERENCES
50.63 (Ph), 167.46 [С(O)NH ]. MALDI TOF/TOF
2
+
mass spectrum, m/z (I , %): 232.100 [М + K] .
rel
2
-({[2-(Aminocarbonyl)phenyl]amino}methyl-
1
. Petersen, H., Syntesis, 1973, vol. 5, p. 243. doi 10.1055/
s-1973-22190
amino)benzamide (9). Yield 0.07 g (70%, method b),
white amorphous substance, mp 158‒162°С. IR
spectrum, cm : 3374, 3178, 2923‒2854, 1615, 1577,
462, 1377, 1276, 1155, 1061, 743, 636. Н NMR
spectrum (DMSO-d ), δ, ppm: 4.72 t (2Н, HNСH NH,
J = 4.0 Hz), 6.58 t (2Н, HC , J = 8.0 Hz), 6.86 d
2Н, HC , J = 8.0 Hz), 7.28 t (2Н, HC , J =
.0 Hz), 7.59 d (2Н, HC , J = 8.0 Hz), 7.13 and 7.82
Ar
br. s (4Н, NH ), 8.59 t (2Н, HN, J = 6.0 Hz).
–
1
2. Garibov, E.N., Rzaeva, I.A., Shykhaliev, N.G., Kuliev, A.I.,
Farzaliev, V.M., and Allakhverdiev, M.A., Russ. J.
Appl. Chem., 2010, vol. 83, no. 4, p. 707. doi 10.1134/
S1070427210040245
1
1
6
2
3
3
Ar
3
. El-Shamy, I.E., Abdel-Mohsen, A.M., Alsheikh, A.A.,
Fouda, M.M.G., Al-Deyab, S.S., El-Hashash, M.A., and
Jancar, J., Dyes and Pigments, 2015, vol. 113, p. 357.
doi 10.1016/j.dyepig.2014.08.026
3
3
(
8
Ar Ar
3
3
13
С
2
NMR spectrum (DMSO-d6), δ, ppm: 51.63
HNСH NH), 112.27 (Ph), 115.06 (Ph), 115.32 (Ph),
4. Ertan, M., Tayhan, A.B., and Yulug, N., Arch. Pharm.,
(
1990, vol. 323, p. 605. doi 10.1002ardp.19903230910
2
1
29.53 (Ph), 132.93 (Ph), 148.94 (Ph), 171.88
5
. Gullapelli, K., Brahmeshwari, G., Ravichander, M., and
Kusuma, U., Egypt. J. Basic Appl. Sci., 2017, vol. 4,
p. 303. doi 10.1016/j.ejbas.2017.09.002
[С(O)NH ]. MALDI TOF/TOF mass spectrum, m/z
2
+
(I , %): 283.260 [М ‒ H] .
rel
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 3 2019

3
84
KHAIRULLINA et al.
6
. Martinovich, Yu.A., Ramsh, S.M., Hamoud, F.,
16. McKerrecher, D., Allen, J.V., Caulkett, P.W.R., Do-
nald, C.S., Fenwick, M.L., Grange, E., Johnson, K.M.,
Johnstone, C., Jones, C.D., Pike, K.G., Rayner, J.W.,
and Walker, R.P., Bioorg. Med. Chem. Lett., 2006,
vol. 16, p. 2705. doi 10.1016/j.bmcl.2006.02.022
Fundamenskii, V.S., Gurzhii, V.V., Zakharov, V.I., and
Khrabrova, E.S., Russ. J. Org. Chem., 2018, vol. 54,
no. 6, p. 878. doi 10.1134/S107042801806009X
7. Kaye, P.T. and Nocanda, X.W., Arkivoc, 2000, vol. 6,
p. 930.
17. Nishimura, T., Iino, T., Mitsuya, M., Bamba, M.,
Watanabe, H., Tsukahara, D., Kamata, K., Sasaki, K.,
Ohyama, S., Hosaka, H., Futamura, M., Nagata, Y., and
Eiki Junichi, Bioorg. Med. Chem. Lett., 2009, vol. 19,
p. 1357. doi 10.1016/j.bmcl.2009.01.053
8
. Sasaki Sh.-ichi, Mizuno, M., Naemura, K., and Tobe, Yo,
J. Org. Chem., 2000, vol. 65, no. 2, p. 275. doi 10.1021/
jo991237k
. Kabha, E., Jacquement, C., Pembouong, G., Mignet, N.,
Scherman, D., and Herscovici, J., Bioorg. Med. Chem.,
9
1
8. More, P., Patil, A., and Salunkhe, R., RSC Adv., 2014,
vol. 96, no. 4, p. 63039. doi 10.1039/c4ra09514f
2
008, vol. 16, p. 4003. doi 10.1016/j.bmc.2008.01.029
1
9. Khairullina, R.R., Geniyatova, A.R., Ibragimov, A.G.,
and Dzemilev, U.M., Russ. J. Org. Chem., 2013,
vol. 49, no. 6, p. 904. doi 10.1134/S1070428013060171
1
0. Farzaliev, V.M., Allakhverdiev, M.A., Magerramov, A.M.,
Shirinova, N.A., Dzavadova, L.A., Rzaeva, I.A.,
Khalilova, A.Z., and Aliev, F.Y., Russ. J. Appl. Chem.,
2
001, vol. 74, no. 1, p. 114. doi 10.1023/
20. Khairullina, R.R., Geniyatova, A.R., Ibragimov, A.G.,
and Dzemilev, U.M., Chem. Heterocl. Compd., 2014,
vol. 50, no. 5, p. 715. doi 10.1007/s10593-014-1525-0
A:1012764404658
1
1
1. Walter, A.M. and Heilmayer, L., Antibiotika Fibel,
Stuttgart: Thieme Verlag, 1965, p. 419.
21. Khairullina, R.R., Geniyatova, A.R., Meshcheryakova, E.S.,
Khalilov, L.M., Ibragimov, A.G., and Dzemilev, U.M.,
Russ. J. Org. Chem., 2015, vol. 51, no. 1, p. 116. doi
2. Kiyokawa, Sh., Hirata, Y., Nagaoka, Y., Shibano, M.,
Taniguchi, M., Yasuda, M., Baba, K., and Uesato, Sh.,
Bioorg. Med. Chem., 2010, vol. 18, p. 3925. doi
1
0.1134/S1070428015010200
1
0.1016/j.bmc.2010.04.033
22. Khairullina, R.R., Tyumkina, T.V., Geniyatova, A.R.,
Mullagil’dina, F.K., and Ibragimov, A.G., Russ. J. Gen.
Chem., 2019, vol. 89, no. 2, p. 202. doi 10.1134/
S0044460X19020069
1
1
3. Cai, J., Wei, H., Hong, K.H., Wu, X., Cao, M., Zong, X.,
Li, L., Sun, C., Chen, J., and Ji, M., Eur. J. Med. Chem.,
2
4. Caldini, R., Fanti, E., Magnelli, L., Barletta, E.,
Tanganelli, E., Zampieri, M., and Chevanne, M.,
Vascular Cell., 2011, vol. 3, p. 12. doi 10.1186/2045-
015, vol. 96, p. 1. doi 10.1016/j.ejmech.2015.04.002
2
3. Khairullina, R.R., Geniyatova, A.R., Tyumkina, T.V.,
Karamzina, D.S., Ibragimov, A.G., and Dzhemilev, U.M.,
Tetrahedron, 2017, vol. 73, no. 50, p. 7079. doi
1
0.1016/j.tet.2017.10.068
8
24X-3-12
2
4. Tramontini, M. and Angiolini, L., Tetrahedron, 1990,
vol. 46, p. 1791. doi 10.1016/S0040-4020(01)89752-0
25. Tramontini, M., Synthesis, 1973, no. 12, p. 703. doi
1
5. Mabkhot, Y.N., Al-Majid, A.M., Barakat, A., Al-
Showiman, S.S., Al-Har, M.S., Radi, S., Naseer, M.M.,
and Hadda, T.B., Int. J. Mol. Sci., 2014, vol. 15,
p. 1503. doi 10.3390/ijms15035115
10.1055/s-1973-22294
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 89 No. 3 2019