Propylphosphonic anhydride (T3P)-mediated three-component synthesis of hexahydrodibenzo[b,e][1,4]diazepin-1-one derivatives

Article abstract of DOI:10.1007/s10593-020-02650-3

[Figure not available: see fulltext.] In this work, the novel approach via propylphosphonic anhydride (T3P)-promoted synthesis of 1,5-benzodiazepines from o-phenylene-diamine, 5,5-dimethylcyclohexane-1,3-dione (dimedone), and aromatic aldehydes

Full text of DOI:10.1007/s10593-020-02650-3

DOI 10.1007/s10593-020-02650-3
Chemistry of Heterocyclic Compounds 2020, 56(2), 237–240
Propylphosphonic anhydride (T3P®)-mediated three-component
synthesis of hexahydrodibenzo[b,e][1,4]diazepin-1-one derivatives
Viktor Hazai1, Tímea Szabó1, Balázs Volk1, Mátyás Milen1*
1 Directorate of Drug Substance Development, Egis Pharmaceuticals Plc.,
P. O. Box 100, Budapest 1475, Hungary; e-mail: milen.matyas@egis.hu
Submitted August 28, 2019
Accepted after revision January 21, 2020
Published in Khimiya Geterotsiklicheskikh Soedinenii,
2020, 56(2), 237–240
NH2
Me
Me
H
N
NH2
O
HN
Ar
H
O
Ar
32–92%
15 examples
O
O
O
P
P
O
P
O
Me
Me
O
Pr
Pr
Pr
O
O
In this work, the novel approach via propylphosphonic anhydride (T3P®)-promoted synthesis of 1,5-benzodiazepines from o-phenylene-
diamine, 5,5-dimethylcyclohexane-1,3-dione (dimedone), and aromatic aldehydes has been studied. The reaction conditions were
optimized and the scope of the reaction was extended to various aromatic aldehydes. The synthesized compounds were obtained in
reasonable to good yields.
Keywords: 1,5-benzodiazepines, nitrogen heterocycles, propylphosphonic anhydride (T3P®), three-component synthesis.
1,5-Benzodiazepines represent an important class of
pharmaceuticals and biologically active compounds.1,2
They possess anxyolitic,3 antidepressive,4 antiepileptic,5
antiviral,6 and anti-inflammatory7 properties. A possible
way to prepare hexahydrodibenzo[b,e][1,4]diazepin-1-ones, an
important subfamily of 1,5-benzodiazepines, is the multi-
component reaction of o-phenylenediamine (1), 5,5-di-
methylcyclohexane-1,3-dione, otherwise called dimedone
(2), and an aldehyde (3) (Scheme 1). This reaction has been
described using many different catalysts, such as graphene
oxide nanosheets,8 sulfated polyborate,9 1-methyl-2-pyr-
and in ionic liquids under ultrasound irradiation.22 It is also
worth mentioning that the first enantioselective synthesis
of 4-substituted 1,5-benzodiazepines starting from
o-phenylenediamine (1), dimedone (2), and aldehydes 3
was described by Wang and coworkers in 2014.23
Scheme 1
rolidinium
hydrogen
sulfate
([H-NMP][HSO4]),10
L-proline,11 zinc sulfide nanoparticles,12,13 tris(hydrogen-
sulfato) boron [B(HSO4)3],14 chitosan-supported superpara-
magnetic iron oxide nanocomposite,15 Fe(OTs)3/SiO2,16
lanthanum compounds,17 graphene-based mesoporous TiO2
nanocomposite,18 and silica-supported NiO nanocompo-
site.19 The reaction proceeded effectively with the
previously mentioned catalysts and in some cases micro-
wave irradiation was applied for heating.19,20 Furthermore,
this reaction was accomplished in a deep eutectic solvent21
Propylphosphonic anhydride (T3P®) is a versatile
coupling agent and water scavenger that has been used in
various chemical transformations.24‒26 In our previous work,
T3P® was successfully used in several multicomponent
reactions.27‒30 Herein, we report the study on T3P®-assisted
three-component reaction of o-phenylenediamine (1),
dimedone (2), and aromatic aldehydes 3.
0009-3122/20/56(2)-0241©2020 Springer Science+Business Media, LLC
241

Chemistry of Heterocyclic Compounds 2020, 56(2), 237–240
Initially, we investigated the reaction with benzaldehyde
Changing the ratio of the starting materials did not
increase the yields (entries 15–17). The last parameters of
the optimization was the temperature and the type of
heating. The reaction at ambient temperature proceeded in
lower yield (entry 18). Furthermore, the microwave heating
did not lead to better result, either (Table 1, entry 19).
After having established optimal reaction conditions, the
substrate scope of the reaction was investigated with
respect to various aromatic aldehydes (Table 2). In most of
the cases, the prepared derivatives 4a–o could be isolated
in good yields. Substituents, such as fluoro, chloro, tri-
fluoromethyl, nitro, cyano, and phenoxy were compatible
with the reaction conditions. However, when 2-fluoro-
benzaldehyde (3b) and the bulky fluorene-2-carbox-
aldehyde (3o) were applied as the starting materials, the
appropriate products 4b and 4o were obtained in only 32
and 55% yields, and unidentified byproducts have been
detected (Table 2).
(3a) in various solvents in order to optimize the reaction
conditions, and the results are listed in Table 1. When the
reaction was conducted in boiling EtOAc for 2 h, the
desired product 4a was isolated in 33% yield (Table 1,
entry 1). Similarly poor yields were obtained in EtOH,
MTBE, MeCN, PhMe, and BMIMOTf (1-butyl-3-methyl-
imidazolium trifluoromethanesulfonate) ionic liquid
(entries 2‒6). The reaction in THF gave product 4a only in
moderate yield (entry 7). Finally, several commonly used
halogenated solvents were tested for this transformation
(entries 8‒11). The best yield was achieved in CHCl3
(76%, entry 9), therefore this solvent was used in the
further optimization steps.
Next, the effect of the amount of T3P®, the ratio of the
starting materials, and the temperature were investigated.
When the reaction was carried out in boiling CHCl3 for 2 h
without T3P®, compound 4a was obtained only in 5% yield
(entry 12). The yield increased to 69% when 1 equiv of
T3P® was used as the promoter (entry 13). Further increase
of the amount of T3P® to 2 and 4 equiv gave corresponding
product 4a in 76 and 81% yields, respectively (entries 9,
14). Using 4 equiv of T3P® resulted in only a few percent
increase in yield, therefore 2 equiv were used for further
studies.
Although the exact mechanism of the T3P®-assisted
three-component reaction of o-phenylenediamine (1),
dimedone (2), and benzaldehyde (3a) is unknown at this
stage, based on the related literature,12,16,20 we propose here
a possible reaction pathway (Scheme 2). In the first step,
the T3P®-promoted condensation of o-phenylenediamine
(1) and dimedone (2) takes place, providing enamine 5 and
QOH as byproduct forming from T3P®. Then, the second
condensation of intermediate 5 and benzaldehyde (3a)
occurs in the presence of T3P® to afford imine 6 and QOH.
Finally, intramolecular cyclization of intermediate 6
followed by proton exchange tautomerization of imine 7
leads to the enamine tautomer of 1,5-benzodiazepine
product 4a.
Table 1. Optimization of the reaction conditions
for the synthesis of compound 4a
Me
Me
Me
H
N
O
Me
NH2
NH2
+
HN
1
O
O
O
Ph
4a
2
Ph
H
3a
T3P®, 1,
Table 2. Investigation of substrate scope with various aromatic
aldehydes 3a–o in the synthesis of compounds 4a–o
2,
3a,
Tempe- Time, Yield,
Entry
Solvent
equiv equiv equiv equiv
rature, °C
Reflux
h
2
%
1
2
2
2
2
2
2
2
2
2
2
2
2
0
1
4
2
2
2
2
4
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.3
1.3
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.1
1.1
1.1
1.1
1.1
EtOAc
EtOH
33
80
Reflux
80
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
33
22
37
40
25
49
53
76
21
46
5
3
MTBE
MeCN
PhMe
4
5
80
Product
Ar
Time, h
Yield, %
76
6
1.1 BMIMOTf
62
Ph
2-FC6H4
3-FC6H4
1
2
1
2
1
1
1
1
1
1
1
1
2
2
1
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
7
1.1
1.1
1.1
THF
Reflux
Reflux
Reflux
80
32
73
8
CH2Cl2
CHCl3
9
4-CF3C6H4
2-ClC6H4
4-ClC6H4
3-Cl-4-FC6H3
2-O2NC6H4
3-O2NC6H4
4-O2NC6H4
2-MeC6H4
4-MeC6H4
4-NCC6H4
4-PhOC6H4
Fluoren-2-yl
70
81
71
10
11
12
13
14
15
16
17
18
19
1.1 1,2-F2C6H4
1.1
1.1
1.1
1.1
1.3
1.3
1.0
1.1
1.1
PhCF3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
80
60
79
83
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
rt
69
81
22
38
69
56
38
80
92
77
83
72
55
MW (75)
242

Chemistry of Heterocyclic Compounds 2020, 56(2), 237–240
Scheme 2
NH2
MgSO4, filtered, and evaporated under reduced pressure. The
O
crude residue was purified by flash column chromatography.
3,3-Dimethyl-11-phenyl-2,3,4,5,10,11-hexahydro-1H-
dibenzo[b,e][1,4]diazepin-1-one (4a). Yield 0.234 g
(76%), pale-yellow crystals, mp 263–265°C (EtOH)
(mp 254–256°C20), Rf 0.56.
Me
Me
O
T3P®
NH2
+
Me
Me
– QOH
NH2
N
H
O
1
2
5
Ph
11-(2-Fluorophenyl)-3,3-dimethyl-2,3,4,5,10,11-hexa-
hydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4b). Yield
0.106 g (32%), white crystals, mp 248–249°C (EtOH),
Rf 0.56. IR spectrum, ν, cm–1: 3289, 1585, 1514, 1383,
T3P®
O
H
N
Ph
N
H
PhCHO
O
3a
H
Me
1
– QOH
N
H
6
1334, 1281, 748. H NMR spectrum, δ, ppm (J, Hz): 1.02
N
Me
Me
(3H, s, CH3); 1.08 (3H, s, CH3); 2.05 (1H, d, J = 15.9,
CH2); 2.19 (1H, d, J = 16.0, CH2); 2.62 (2H, s, CH2); 5.75
(1H, d, J = 6.0, CH); 5.96 (1H, d, J = 6.0, NH); 6.51 (1H,
d, J = 7.6, H Ar); 6.57–6.63 (2H, m, H Ar); 6.72 (1H, t,
J = 7.7, H Ar); 6.81–6.83 (1H, m, H Ar); 6.97 (1H, d,
J = 7.7, H Ar); 7.04–7.05 (1H, m, H Ar); 7.06–7.09 (1H,
m, H Ar); 8.92 (1H, br. s, NH). 13C NMR spectrum, δ, ppm
(J, Hz): 27.6 (CH3); 28.6 (CH3); 32.1 (C-4); 44.3 (CH2);
7
Me
H
N
Ph
O
H
O
P
O
O
P
P
N
H
4a
Q =
O
O
OH
Me
Pr
Pr
Pr
Me
3
In conclusion, the synthesis of 1,5-benzodiazepine
derivatives via a one-pot three-component reaction has
been accomplished in the presence of T3P®. In addition,
the preparation of these remarkable heterocycles has been
achieved by a novel and practical approach with good
substituent tolerance in the aldehyde component.
49.6 (CH2); 50.8 (d, JCF = 3.2, CH); 109.1 (C Ar); 115.2
2
2
(d, JCF = 22.1, C Ar); 120.3 (d, JCF = 28.2, C Ar); 120.8
3
(C Ar); 123.1 (C Ar); 123.6 (d, JCF = 3.0, C Ar); 128.0 (d,
3JCF = 4.2, C Ar); 128.8 (d, JCF = 8.2, C Ar); 131.4 (d,
3
3JCF = 14.3, C Ar); 131.6 (C Ar); 138.2 (C Ar); 155.6
(C Ar); 160.7 (d, JCF = 243.5); 192.2 (C=O). Found, m/z:
337.1710 [M+H]+. C21H22FN2O. Calculated, m/z: 337.1716;
11-(3-Fluorophenyl)-3,3-dimethyl-2,3,4,5,10,11-hexa-
hydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4c). Yield
0.244 g (73%), pale-yellow crystals, mp 250–251°C
(EtOH), Rf 0.54. IR spectrum, ν, cm–1: 3311, 2957, 1581,
1509, 1382, 1153, 752. 1H NMR spectrum, δ, ppm (J, Hz):
1.04 (3H, s, CH3); 1.08 (3H, s, CH3); 2.11 (1H, d, J = 16.0,
CH2); 2.21 (1H, d, J = 15.9, CH2); 2.63–2.57 (2H, m, CH2);
5.70 (1H, d, J = 5.9, CH); 6.24 (1H, d, J = 6.1, NH); 6.53–
6.55 (1H, m, H Ar); 6.57–6.60 (1H, m, H Ar); 6.62–6.64
(1H, m, H Ar); 6.81–6.85 (1H, m, H Ar); 6.86–6.88 (1H,
m, H Ar); 6.90–6.92 (1H, m, H Ar); 6.93–6.94 (1H, m,
H Ar); 7.13–7.17 (1H, m, H Ar); 8.82 (1H, br. s, NH).
13C NMR spectrum, δ, ppm (J, Hz): 27.7 (CH3); 28.6
(CH3); 32.0 (C); 39.7 (C); 44.2 (CH2); 49.6 (CH2); 55.8
(CH); 109.7 (2C Ar); 112.9 (d, 2JCF = 21.0, C Ar); 114.1 (d,
Experimental
IR spectra were obtained on a Bruker Alpha FT-IR
spectrometer in KBr pellets. 1H and 13C NMR spectra were
recorded on a Bruker Avance III HD 600 spectrometer
(600 and 150 MHz, respectively) in DMSO-d6 at room
temperature with TMS as internal standard. COSY,
1H–13C HSQC, and 1H–13C HMBC experiments were
performed on the same spectrometer. High-resolution mass
spectra were recorded on a Bruker O-TOF maXis Ultimate
3000 RS HPLC system with a diode array detector. Mass
spectra were recorded on a Shimadzu LC-20 HPLC-ESI-
MS with an SPD-M20A diode array detector. Melting
points were determined on a Büchi B-540 capillary melting
point apparatus and are uncorrected. Reactions progress
was monitored by TLC on Merck 60 F254 silica gel plates, eluent
CH2Cl2–MeOH, 9:1, visualized with UV light. Purification by
flash column chromatography was carried out using Merck
107736 silica gel 60 H, eluent CH2Cl2–MeOH, 9:1.
All reagents were purchased from commercial sources
and used without further purification. Analytical samples of
new compounds were obtained by recrystallization from
the solvents or solvent mixtures given below in paren-
theses. Analytical data of compounds 4a,d–n coincide with
those reported in the literature.13,20,22,23,31–34
Synthesis of compounds 4a–o (General method).
o-Phenylenediamine (1) (1.0 mmol) was dissolved in CHCl3
(10 ml), then the corresponding aldehyde 3a–o (1.1 mmol),
dimedone (2) (1.0 mmol), and T3P® (Aldrich 50% solution
in EtOAc, 2.0 mmol) were added. The reaction mixture
was heated at reflux. After completion of the reaction
(1–2 h), the mixture was cooled to room temperature and
washed with 10% NaHCO3 solution (10 ml) and H2O
(10 ml). The organic phase was dried over anhydrous
2
2JCF = 21.3, C Ar); 120.1 (d, JCF = 46.3, C Ar); 120.7
(C Ar); 123.0 (C Ar); 123.5 (d, 3JCF = 1.8, C Ar); 129.7 (d,
3JCF = 8.1, C Ar); 131.2 (C Ar); 138.5 (C Ar); 148.0 (d,
3JCF = 5.7, C Ar); 155.2 (C); 162.2 (d, 1JCF = 240.8, C Ar);
192.3 (C=O). Found, m/z: 337.1706 [M+H]+. C21H22FN2O.
Calculated, m/z: 337.1716.
3,3-Dimethyl-11-[(4-trifluoromethyl)phenyl]-2,3,4,5,10,11-
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4d).31
Yield 0.269 g (70%), yellow crystals, mp 288–290°C
(EtOH), Rf 0.51.
11-(2-Chlorophenyl)-3,3-dimethyl-2,3,4,5,10,11-hexa-
hydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4e). Yield
0.285 g (81%), white crystals, mp 237–240°C (EtOH) (mp
235–237°C32), Rf 0.57.
11-(4-Chlorophenyl)-3,3-dimethyl-2,3,4,5,10,11-hexa-
hydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4f). Yield
0.250 g (71%), yellow crystals, mp 251–253°C (EtOH)
(mp 238–240°C22), Rf 0.52.
243

Chemistry of Heterocyclic Compounds 2020, 56(2), 237–240
11-(3-Chloro-4-fluorophenyl)-3,3-dimethyl-2,3,4,5,10,11-
References
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4g).23
Yield 0.222 g (60%), pale-yellow crystals, mp 243–245°C
(EtOH), Rf 0.59.
1. da Silva, E. F., Jr.; da Silva, D. L.; de Aquino, T. M.;
Nogueira Ribiero, Ê. A.; Jelvez Serra, N. S.; de Araújo, J. X.,
Jr. Pinnacle Medicine & Medicinal Sciences 2014, 1, 239.
2. Solomko, Z. F.; Kost, A. N. Chem. Heterocycl. Compd. 1975,
11, 1231. [Khim. Geterotsikl. Soedin. 1975, 1443.]
3. Robertson, M. M. Epilepsia 1986, 27(s1), S27.
4. Schmitz, A. Ment. Health Clin. 2016, 6, 120.
5. Gauthier, A. C.; Mattson, R. H. CNS Neurosci. Ther. 2015,
21, 543.
6. Schimer, J.; Cígler, P.; Veselý, J.; Šašková, K. G.; Lepšík, M.;
Brynda, J.; Řezáčová, P.; Kožíšek, M.; Císářová, I.;
Oberwinkler, H.; Kraeusslich, H.-G.; Konvalinka, J. J. Med.
Chem. 2012, 55, 10130.
7. Bhat, I. K.; Kumar, A. Asian J. Pharm. Clin. Res. 2016, 9(4), 63.
8. Kausar, N.; Mukherjee, P.; Das, A. R. RSC Adv. 2016, 6,
88904.
9. Indalkar, K. S.; Patil, M. S.; Chaturbhuj, G. U. Tetrahedron
Lett. 2017, 58, 4496.
10. Naeimi, H.; Foroughi, H. Chin. J. Catal. 2015, 36, 734.
11. Nagarju, S.; Perumal, O. P.; Divakar, K.; Paplal, B.;
Kashinath, D. New J. Chem. 2017, 41, 8993.
12. Naeimi, H.; Foroughi, H. New J. Chem. 2015, 39, 1228.
13. Naeimi, H.; Foroughi, H. Res. Chem. Intermed. 2016, 42,
3999.
3,3-Dimethyl-11-(2-nitrophenyl)-2,3,4,5,10,11-hexa-
hydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4h). Yield
0.285 g (79%), orange crystals, mp 230–232°C (EtOH)
(mp 230–232°C13), Rf 0.58.
3,3-Dimethyl-11-(3-nitrophenyl)-2,3,4,5,10,11-hexa-
hydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4i). Yield
0.303 g (83%), yellow crystals, mp 214–217°C (EtOH)
(mp 195–197°C13), Rf 0.54.
3,3-Dimethyl-11-(4-nitrophenyl)-2,3,4,5,10,11-hexa-
hydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4j). Yield
0.289 g (80%), yellow crystals, mp 280–282°C (decomp.,
EtOH–MeOH) (mp 280–281°C13), Rf 0.50.
3,3-Dimethyl-11-(2-methylphenyl)-2,3,4,5,10,11-hexa-
hydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4k). Yield
0.306 g (92%), pale-yellow crystals, mp 263–264°C
(EtOH) (mp 215–217°C33), Rf 0.62.
3,3-Dimethyl-11-(4-methylphenyl)-2,3,4,5,10,11-hexa-
hydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4l). Yield
0.256 g (77%), yellow crystals, mp 244–246°C (EtOH)
(mp 232–235°C20), Rf 0.55.
4-(3,3-Dimethyl-1-oxo-2,3,4,5,10,11-hexahydro-1H-
dibenzo[b,e][1,4]diazepin-11-yl)benzonitrile (4m). Yield
0.284 g (83%), yellow crystals, mp 147–149°C (EtOH)
(mp 225–227°C34), Rf 0.51.
4-(3,3-Dimethyl-11-(4-phenoxyphenyl)-2,3,4,5,10,11-
hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4n).31
Yield 0.295 g (72%), white crystals, mp 245–246°C
(EtOH), Rf 0.49.
14. Karimi-Jaberi, Z.; Hooshmandpour, A. Polycycl. Aromat.
Compd. 2018. DOI: 10.1080/10406638.2018.1441876.
15. Maleki, A.; Kamalzare, M. Tetrahedron Lett. 2014, 55, 6931.
16. Tarannum, S.; Siddiqui, Z. N. RSC Adv. 2015, 5, 74242.
17. Singh, A.; Palakollu, V.; Pandey, A.; Kanvah, S.; Sharma, S.
RSC Adv. 2016, 6, 103455.
18. Shoeb, M.; Mobin, M.; Ali, A.; Zaman, S.; Naqvi, A. H. Appl.
Organomet. Chem. 2018, 32, e3961.
19. Nasir, Z.; Ali, A.; Shakir, M.; Wahab, R.; Shamsuzzaman;
Lutfullah New J. Chem. 2017, 41, 5893.
20. Zhu, X.-T.; Liu, J.-Y.; Jiang, B.; Tu, S.-J. J. Heterocycl.
Chem. 2015, 52, 92.
11-(9H-Fluoren-2-yl)-3,3-dimethyl-2,3,4,5,10,11-hexa-
hydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4o). Yield
0.224 g (55%), off-white crystals, mp 283–285°C (decomp.,
EtOH), Rf 0.56. IR spectrum, ν, cm–1: 3327, 2952, 1638,
21. Shaabani, A.; Hooshmand, S. E.; Nazeri, M. T.; Afshari, R.;
Ghasemi, S. Tetrahedron Lett. 2016, 57, 3727.
22. Sarhandi, S.; Fekri, L. Z.; Vassaly, E. Acta Chim. Slov. 2018,
65, 246.
1
1540, 1391, 1335, 1292, 1172, 1123, 890, 735. H NMR
spectrum, δ, ppm (J, Hz): 1.07 (3H, s, CH3); 1.10 (3H, s,
CH3); 2.12 (1H, d, J = 15.9, CH2); 2.22 (1H, d, J = 15.9,
CH2); 2.59–2.65 (2H, m, CH2); 3.74 (2H, s, CH2); 5.78
(1H, d, J = 5.9, CH); 6.23 (1H, d, J = 6.1, NH); 6.53–6.59
(3H, m, H Ar); 6.94–6.96 (1H, m, H Ar); 7.10 (1H, d, J = 7.9,
H Ar); 7.22–7.24 (1H, m, H Ar); 7.28–7.31 (1H, m, H Ar);
7.33 (1H, s, H Ar); 7.49 (1H, d, J = 7.4, H Ar); 7.61 (1H, d,
J = 7.9, H Ar); 7.73 (1H, d, J = 7.6, H Ar); 8.81 (1H, s,
NH). 13C NMR spectrum, δ, ppm (J, Hz): 27.7 (CH3); 28.7
(CH3); 32.0 (C); 36.4 (CH2); 44.3 (CH2); 49.7 (CH2); 56.4
(CH); 110.5 (C); 119.4 (CH Ar); 119.7 (CH Ar); 119.9
(CH Ar); 120.2 (2CH Ar); 120.8 (CH Ar); 122.8 (CH Ar);
124.2 (CH Ar); 125.2 (CH Ar); 126.5 (CH Ar); 126.0 (CH
Ar); 126.8 (CH Ar); 131.4 (C Ar); 138.8 (C Ar); 139.1 (C
Ar); 141.1 (C Ar); 142.7 (C Ar); 143.1 (C Ar); 144.2
(C Ar); 154.9 (C Ar); 192.3 (C=O). Found, m/z: 407.2108
[M+H]+. C28H27N2O. Calculated, m/z: 407.2123.
23. Wang, Y.; Tu, M.-S.; Shi, F.; Tu, S.-J. Adv. Synth. Catal.
2014, 356, 2009.
24. Waghmare, A. A.; Hindupur, R. M.; Pati, H. N. Rev. J. Chem.
2014, 4, 53.
25. Basavaprabhu; Vishwanatha, T. M.; Panguluri, N. R.;
Sureshbabu, V. V. Synthesis 2013, 1569.
26. Panther, J.; Rechmann, J.; Müller, T. J. J. Chem. Heterocycl.
Compd. 2016, 52, 897. [Khim. Geterotsikl. Soedin. 2016, 52, 897.]
27. Milen, M.; Ábrányi-Balogh, P.; Dancsó, A.; Frigyes, D.;
Pongó, L.; Keglevich, G. Tetrahedron Lett. 2013, 54, 5430.
28. Milen, M.; Dancsó, A.; Földesi, T.; Slégel, P.; Volk, B.
Tetrahedron 2016, 72, 5091.
29. Milen, M.; Dancsó, A.; Földesi, T.; Volk, B. Tetrahedron
2017, 73, 70.
30. Varga, V.; Milen, M.; Ábrányi-Balogh, P. Tetrahedron Lett.
2018, 59, 3683.
31. Bonfanti, J.-F.; Doublet, F. M. M.; Nyanguile, O.;
Raboisson, P. J.-M. B.; Rebstock, A.-S. H. M.; Boutton, C. W. M.
WO Patent 2007026024A2. Chem. Abstr. 2007, 146, 316950.
32. Savari, A.; Heidarizadeh, F.; Pourreza, N. Polyhedron 2019,
166, 233.
Supplementary information file containing 1H and
1
1
13C NMR, COSY, H–13C HSQC, H–13C HMBC, and IR
spectra of all synthesized compounds 4a–o is available at
the journal website at http://link.springer.com/journal/10593.
33. Arellano, M. d. R.; Martínez, R.; Cortés, E. J. Heterocycl.
Chem. 1982, 19, 321.
34. Kausar, N.; Mukherjee, P.; Das, A. R. RSC Adv. 2016, 6, 88904.
244