Mannich Reaction with Enaminones: Convenient Synthesis of Functionalized Tetrahydro-pyrimidines, Dihydro-1,3-oxazines, and Dihydro-1,2,4-triazepines

Article abstract of DOI:10.1002/jhet.3377

A series of tetrahydropyrimidines and bis-(tetrahydropyrimidines) was synthesized by Mannich reaction of sec-emaminones with formaldehyde and the appropriate amine or diamine. Whereas the reaction with formaldehyde gave the dihydro-1,3-oxazine. Tetrahydro

Full text of DOI:10.1002/jhet.3377

Month 2018
Mannich Reaction with Enaminones: Convenient Synthesis of Function-
alized Tetrahydro-pyrimidines, Dihydro-1,3-oxazines, and Dihydro-1,2,4-
triazepines
Elsayed M. Afsah,*
El-Sayed I. El-Desoky, Hassan A. Etman, Ibrahim Youssef,
and Ahbarah M. Soliman
Chemistry Department, Faculty of Science, Mansoura University, Mansoura ET-35516, Egypt
*
E-mail: emafsah@yahoo.com
Received June 5, 2018
DOI 10.1002/jhet.3377
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
A series of tetrahydropyrimidines and bis-(tetrahydropyrimidines) was synthesized by Mannich reaction
of sec-emaminones with formaldehyde and the appropriate amine or diamine. Whereas the reaction with
formaldehyde gave the dihydro-1,3-oxazine. Tetrahydropyrimidines incorporating a phenolic Mannich base
were obtained by Mannich reaction of the appropriate tetrahydropyrimidine. The bis(sec-enaminones) were
used as precursors in synthesis of bis(tetrahydropyrimidines) and bis(dihydro-1,3-oxazines). Treatment of
the appropriate sec-emaminone or bis(sec-enaminone) with hydrazine hydrate or phenylhydrazine and a suit-
able aldehyde afforded dihydro-1,2,4-triazepines and the bis(dihydro-1,2,4-triazepines).
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
construction and modification of heterocyclic systems,
natural products, and drug design [17–21]. Although the
utility of tertiary enaminones as intermediates in
synthesis of a variety of heterocycles was reported [22–
30], the use of secondary enaminones as synthetic
intermediates was less widely recognized and had seen
limited use [31,32]. In particular, Mannich reaction with
secondary enaminones, derived from 1,3-indandione [33]
or dimedone [34], has been reported as a route to fused
Owing to the immense importance and varied
bioactivities exhibited by the nitrogen-containing
heterocycles, efforts have been made to generate libraries
of these compounds and screened them for potential
biological activities. Because of their frequent occurrence
in pharmaceutical research, the synthesis and
functionalization of specific heterocycles such as
quinolines [1–3], pyrazolines [4–8], pyrimidines [9–13],
tetrahydropyrimidines,
dihydro-1,3-oxazines,
and
1,3-oxazines [14,15], and 1,2,4-triazepines [16] have
benzodiazepines. [33,35,36].
received significant attention.
In connection with our studies in the area of Mannich
bases [37–45], the synthetic potential of secondary
enaminones as intermediates in heterocyclic synthesis
was further investigated, particularly, for the synthesis of
On the other hand, the chemistry of enaminones has
been the subject of wide and increasing interest because
of their importance as versatile synthetic intermediates for
©
2018 Wiley Periodicals, Inc.

E. M. Afsah, E.-S. I. El-Desoky, H. A. Etman, I. Youssef, and A. M. Soliman
Vol 000
some new functionalized tetrahydropyrimidines, dihydro-1,3-
oxazines, and dihydro-1,2,4-triazepines of pharmaceutical
interest.
benzene (4a) and the 1-p-anisyl analogue 4b, respectively.
A similar reaction of 2a with ethylenediamine takes place
yielding the bis-(1,2,3,4-tetrahydropyrimidine) (5). The
mass spectra of 3a–3f, 4a, 4b, and 5 contain peaks of the
respective molecular ions, it underwent fragmentation
pattern that supported their structures.
RESULTS AND DISCUSSION
On the other hand, the reaction of 2c with formaldehyde
A series of 1-phenyl-3-(arylamino)propenones (2a–e)
was prepared by transamination reaction between the
tertiary enaminone 1 and the appropriate primary
aromatic amine. It was found that Mannich reaction of
the secondary enaminones 2a–c with formaldehyde and
the appropriate primary amine afforded a series of 5-
benzoyl-1,3-diaryl-1,2,3,4-tetrahydropyrimidines (3a–3e).
A similar reaction of 2b with ammonium acetate gave 5-
benzoyl-1-p-tolyl-1,2,3,4-tetrahydropyrimidine (3f) (Scheme 1).
This reaction is of considerable preparative value, as
numerous amines can be used in the Mannich reaction
with the secondary enaminones (Scheme 1).
in a molar ratio (1:2) led to the formation of 5-benzoyl-
1
3-(p-anisyl)-3,6-dihydro-2H-1,3-oxazine (6). The
H
NMR spectrum supported its structure as it revealed four
singlets at δ = 3.80 (3H, OCH ), 4.40 (2H, 6-H ), 5.01
3
2
(2H, 2-H ), and 7.54 ppm (1H, 4-H).
2
The interest in the pharmacological activity of phenolic
Mannich bases and related compounds prompted us to
prepare 5-benzoyl-1-(4-hydroxyphenyl)-3-(p-tolyl)-1,2,3,4-
tetrahydropyrimidine (7), which was used as a precursor for
the synthesis of tetrahydropyrimidines incorporating a
phenolic Mannich base as a structural unit (Scheme 2). This
has been achieved by treating 7 with dimethylamine,
piperidine or morpholine, and formaldehyde to give the
phenolic Mannich bases 8a–c or the phenolic bis-(Mannich
bases) 9a–c, respectively, depending on the molar ratio of
the reactants. In addition, Mannich reaction of 2d with
formaldehyde and p-aminophenol gave 5-benzoyl-1,3-di(4-
hydroxyphenyl)-1,2,3,4-tetrahydropyrimidine (10), which
was treated with formaldehyde and piperidine or
morpholine in a molar ratio (1:4:4) to give the tetra
(Mannich bases) 11a and 11b, respectively.
The structure of 3a–3f was confirmed by analytical and
1
spectral data. The H NMR spectrum of 3a (R = CH Ph)
2
—as an example—displays four singlets at δ = 3.80 (2H,
4
7
-H ), 3.96 (2H, Ph-CH ), 4.53 (2H, 2-H ), and
.67 ppm (1H, 6-H), and the C NMR spectrum gave
2
2
2
1
3
further support to its structure. In addition, Mannich
reaction of 2b and 2c with p-phenylenediamine and
formaldehyde proceeded equally well, providing 1,4-
bis(5-benzoyl-1-p-tolyl-1,2,3,4-tetrahydropyrimidin-3-yl)-
Scheme 1. Mannich reaction with secondary enaminones 2a–e.
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Mannich Reaction with Enaminones
Scheme 2. Synthesis of the phenolic Mannich bases 8, 9, and 11.
The analytical and spectral data of compounds 8–11 are
consistent with their structures. The formation of 8, 9, and
synthesized and studied with interest centered on their
potential pharmaceutical activity [39,44,46–50].
1
1 is of interest, because a variety of compounds having a
In connection with the present study, the transamination
reaction between 1 and p-phenylenediamine lead to the
phenolic Mannich base as a structural unit have been
Scheme 3. Synthesis of bis(tetrahydropyrimidines) (13a–f and 16a–d) and bis(dihydro-1,3-oxazines) (14 and 17).
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E. M. Afsah, E.-S. I. El-Desoky, H. A. Etman, I. Youssef, and A. M. Soliman
Vol 000
0
formation of N,N -(bis-(1-phenylprop-2-en-1-one-3-yl))-
2-aminopyridine to give the target compounds 20a and
20b, respectively.
p-phenylenediamine (12). The Mannich reaction of the
bis (secondary enaminone) 12 is of particular interest,
A similar reaction of 19a and 19b with formaldehyde
and ammonium acetate lead to the formation of 1,4-
phenylenebis((1-(p-tolyl)-1,2,3,4-tetrahydropyrimidin-5-
yl)methanone) (21a) and the 1-(pyridin-2-yl) analogue 21b,
respectively. On the other hand, 1,4-phenylenebis((3-
because
it
provides
access
to
bis(1,2,3,4-
tetrahydropyrimidines) (Scheme 3). This has been
realized by treating 12 with the appropriate primary
amine and formaldehyde, to give a series of 1,4-bis(5-
benzoyl-3-aryl-1,2,3,4-tetrahydropyrimidin-1-yl)-
(p-tolyl)-3,6-dihydro-2H-1,3-oxazin-5-yl)methanone)
(22)
benzenes (13a–f). The mass spectra of compounds 13a–f
contain peaks of the respective molecular ions, and the
IR and H NMR spectral data supported their structures.
was obtained by the reaction of 19a with formaldehyde in a
molar ratio (1:4).
1
In the course of this study, it has been found that a
convenient route to the dihydro-1,2,4-triazepine ring
system starts with secondary enaminones of the type 2.
Therefore, compounds 2b and 2e were treated with
hydrazine hydrate and subsequently with formaldehyde
under mild conditions to give 7-phenyl-4-(p-tolyl)-3,4-
dihydro-2H-1,2,4-triazepine (23a) and the 4-(pyridin-2-
yl) analogue 23b, respectively. A similar reaction takes
place on treating 2c with phenylhydrazine and glutaric
dialdehyde yielding 1,3-bis(4-(4-methoxyphenyl)-2,7-
diphenyl-3,4-dihydro-2H-1,2,4-triazepin-3-yl) propane
(24) (Scheme 5).
In addition, the synthesis of 1,4-bis(5-benzoyl-3,6-
dihydro-2H-1,3-oxazine-3-yl)-benzene (14) has been
achieved by treating 12 with formaldehyde in a molar
ratio (1:4). The mass spectrum of 14 exhibited a
+
molecular ion peak at m/z = 452 [M] and a
fragmentation pattern that supported its structure.
A similar approach was used for the synthesis of the
bis(1,2,3,4-tetrahydropyrimidines) (16a–d) and 1,2-bis(5-
benzoyl-3,6-dihydro-2H-1,3-oxazine-3-yl)-ethane
(17),
starting from the previously reported bis (secondary
enaminone) 15 [51], as depicted in Scheme 3.
The advantage of this route to bis(tetrahydropyrimidines) is
further illustrated by the synthesis of the bis compounds
In line with this, the bis (secondary enaminone) 15 was
treated with hydrazine hydrate and subsequently with
formaldehyde to afford 1,2-bis(7-phenyl-2,3-dihydro-4H-
1,2,4-triazepin-4-yl) ethane (25).
The mass spectra of 23a, 23b, 24, and 25 revealed
molecular ion peaks at m/z = 263, 250, 750, and 372,
respectively, and the fragmentation pattern agreed with
the proposed structures. A practical advantage of the
20a,b and 21a,b (Scheme 4). This has been realized via a
reaction sequence that involves the transamination
reaction between the bis(enaminone) 18 [52] and p-
toluidine or 2-aminopyridine to give the bis (secondary
enaminones) 19a and 19b, which were subjected to
Mannich reaction with formaldehyde and p-toluidine or
Scheme 4. Synthesis of bis(tetrahydropyrimidines) (20a–b and 21a–b) and bis(dihydro-1,3-oxazine) (22).
Journal of Heterocyclic Chemistry
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Month 2018
Mannich Reaction with Enaminones
Scheme 5. Synthesis of dihydro-2H-1,2,4-triazepines 23–25.
reactions leading to the dihydro-1,2,4-triazepines 23–25 is
that it is carried out sequentially, and it is often
unnecessary to isolate the intermediate hydrazones.
(15 mL) was heated under reflux for 5 h and left to
stand at room temperature overnight. The product
filtered off and crystallized from ethanol to give
compounds 2a–e.
1
-Phenyl-3-(phenylamino)prop-2-en-1-one (2a).
Yield
7%, (yellow crystals), mp 140–141°C (141–142°C
53]); IR (KBr): ν = 3447 (NH), 1637 (C═O), 1600
EXPERIMENTAL
7
[
ꢀ
1
1
All melting points (uncorrected) were determined on a
Gallenkamp electric melting point apparatus (Sanyo
(C═C), 1585, 1549, 1238 cm
;
H NMR (CDCl3)
δ = 6.05 (d, 1H, 2-H), 7.09–7.94 (m, 10H, Ar─H), 7.79
d, 1H, 3-H), 12.20 ppm (s, 1H, NH); MS (EI, 70 eV):
Gallenkamp,
Southborough,
UK).
Elemental
(
+
+
microanalyses were carried out on a Carlo Erba 1108
Elemental Analyzer (Heraeus, Hanau, Germany) at the Mi-
croanalytical Unit, Al-Azhar University. Infrared spectra
m/z (%) = 223 (36) [M] , 222 (100) [M ꢀ 1] , 146 (45)
+
[
M-Ph] , 105 (16), 77(54). Anal. Calcd for C H NO
15 13
(223.28): Calcd C 80.69, H 5.87, N 6.27. Found C 80.59,
H 5.78, N 6.19.
were measured on a Mattson 5000 FTIR spectrometer
1
(
Mattson Instruments, Inc., Madison, WI, USA).
H
1
-Phenyl-3-(p-tolylamino)prop-2-en-1-one (2b).
Yield
13
and C NMR data were obtained in CDCl or (DMSO-
3
90%, (yellow powder), mp 155–156°C (157–159°C
d6) solution on a Varian XL 400 MHz instrument (Varian,
[53]); IR (KBr): ν = 3436 (NH), 1662 (C═O), 1630
ꢀ
1
1
Inc., CA, USA) using tetramethylsilane as internal stan-
(C═C), 1582, 1511, 1255 cm
;
H NMR (CDCl3)
dard. Chemical shifts are reported in ppm (δ) downfield
from internal tetramethylsilane. The mass spectra were re-
corded on a GC–MS QP–1000 EX Shimadzu instrument
δ = 2.35 (s, 3H, CH ), 6.02 (d, 1H, 2-H), 7.03–7.96 (m,
3
9
H, Ar─H), 7.89 (d, 1H, 3-H), 12.21 ppm (s, 1H, NH);
+
MS (EI, 70 eV): m/z (%) = 237 (40) [M] , 236 (100)
+
+
(Shimadzu, Tokyo, Japan). The course of the reaction
[
M ꢀ 1] , 160 (38) [M-Ph] , 105 (20), 91 (16), 77 (42).
and the purity of the synthesized compounds were moni-
tored by thin-layer chromatography using EM science sil-
ica gel coated plates, 0.25 nm, 60 GF 254 (Merck,
Darmstadt, Germany) with visualization by irradiation with
an ultraviolet lamp. Compounds 20a, 20b, 21a, 21b, 22,
Anal. Calcd for C H NO (237.30): Calcd C 80.98, H
16 15
6
.37, N 5.90. Found C 80.83, H 6.21, N 5.82.
3
-((4-Methoxyphenyl)amino)-1-phenylprop-2-en-1-one
(2c). Yield 94%, (pale-green powder), mp 144–146°C
(147–148°C [54]); IR (KBr): ν = 3435 (NH), 1616
ꢀ
1
1
2
3a, 23b, 24, and 25 are of limited solubility in common
(C═O), 1598, 1508, 1249 cm
;
H NMR (CDCl3):
1
H NMR solvents. Compounds 1 [23], 2a, 2b [53], 2c
54], 3a–3c [31], 15 [51], and 18 [52] were prepared as
δ = 3.81 (s, 3H, OCH ), 6.11 (d, 1H, 2-H), 6.91–7.54 (m,
3
[
9H, Ar─H), 7.79 (d, IH, 3-H), 12.22 ppm (s, 1H, NH);
+
previously described.
MS (EI, 70 eV): m/z (%) = 253 (1) [M] , 252 (1)
+
+
Synthesis of the secondary enaminones (2a–e).
A
[M ꢀ 1] , 148 (15) [M-PhCO] , 77 (6). Anal. Calcd for
(253.30): Calcd C 75.87, H 5.97, N 5.53.
Found C 75.80, H 5.81, N 5.46.
solution of the enaminone 1 [23] (0.88 g, 5 mmol) and
the appropriate primary amine (5 mmol) in dioxane
C H15NO
16 2
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E. M. Afsah, E.-S. I. El-Desoky, H. A. Etman, I. Youssef, and A. M. Soliman
Vol 000
ꢀ
1
1
3-((4-Hydroxyphenyl)amino)-1-phenylprop-2-en-1-one
1586, 1561, 1511, 1257 cm
;
H NMR (CDCl3):
(
2d).
Yield 85%, (green crystals), mp 124–125°C; IR
δ = 2.31 (s, 3H, CH ), 3.82 (s, 2H, 4-H ), 4.23 (s, 2H,
3
2
(
(
(
KBr): ν = 3300 (OH), 3457 (NH), 1633 (C═O), 1610
C═C), 1535, 1500 cm ; H NMR (CDCl ): δ = 6.72
d, 1H, 2-H), 6.51–7.73 (m, 9H, Ar─H), 7.81 (d, 1H, 3-
CH Ph), 4.51 (s, 2H, 2-H ), 6.81–7.53 (m, 14H, Ar─H),
2
2
ꢀ
1 1
3
7.66 ppm (s, 1H, 6-H); MS (EI, 70 eV): m/z (%) = 370
+
+
+
(
[
1) [M + 2] , 369 (10) [M + 1] , 368 (46) [M] , 367 (9)
+
+
H), 9.44 (s, 1H, OH), 11.60 ppm (s, 1H, NH); MS (EI,
7
[
(
M ꢀ 1] , 366 (6), 277 (23) [M-CH Ph] , 263 (3) [M-
2
+
+
+
0 eV): m/z (%) = 239 (25) [M] , 222 (100), 162 (30)
M-Ph] , 105 (15), 77 (45). Anal. Calcd for C H NO
239.27): Calcd C 75.30, H 5.48, N 5.85. Found C 75.28,
PhCO] , 105 (18) [PhCO] , 91 (100), 77 (35), 51 (14).
Anal. Calcd for C25 O (368.48): Calcd C 81.49, H
.57, N 7.60. Found C 81.39, H 6.48, N 7.55.
+
15 13 2
H N
24 2
6
H 5.39, N 5.79.
5-Benzoyl-(1,3-di-p-tolyl)-1,2,3,4-tetrahydropyrimidine
(3d).
1
-Phenyl-3-(pyridin-2-ylamino)prop-2-en-1-one (2e).
Yield 92%, (white powder), mp 158–160°C; IR
(KBr): ν = 3221, 1662 (C═O), 1639 (C═C), 1542, 1477,
Yield 60%, (yellow powder), mp 115–117°C; IR (KBr):
ν = 3455 (NH), 1640 (C═O), 1622 (C═C) cm ; H
ꢀ
1
1
ꢀ1
1
1271 cm ; H NMR (CDCl ): δ = 2.27 (s, 3H, CH ),
3 3
NMR (CDCl ): δ = 6.71 (d, 1H, 2-H), 6.82–7.81 (m, 9H,
2.32 (s, 3H, CH ), 4.47 (s, 2H, 4-H ), 5.12 (s, 2H, 2-H ),
3 2 2
3
13
Ar─H), 7.91 (d, 1H, 3-H), 13.01 ppm (s, 1H, NH); MS
6.82–7.50 (m, 13H, Ar─H), 7.63 ppm (s, 1H, 6-H);
C
+
(
EI,70 eV): m/z (%) = 224 (15) [M] , 146 (100) [M-
NMR (CDCl ): δ = 20.4, 20.7 (2CH ), 47.2 (C-4), 66.0
3
3
+
+
C H N] , 119 (40) [M-PhCO] , 105 (10), 78 (65), 77
(C-2), 110.2 (C-5), 118.0, 118.8, 128.1, 128.4, 129.8,
130.1, 130.3, 131.0, 134.4, 139.7, 141.7, 145.2 (all
Ar─C), 146.3 (C-6), 193.2 ppm (C═O); MS (EI, 70 eV):
5
4
(
36). Anal. Calcd for C H N O (224.26): Calcd C
14 12 2
74.98, H 5.39, N 12.49. Found C 74.94, H 5.28, N 12.38.
+
+
Synthesis of the tetrahydropyrimidines (3a–e).
To a
m/z (%) = 370 (4) [M + 2] , 369 (29) [M + 1] , 368 (98)
+
+
+
solution of 2a (0.45 g, 2 mmol), or 2b (0.47 g, 2 mmol),
or 2c (0.50 g, 2 mmol), in ethanol (20 mL), formalin 37%
[M] , 291 (2) [M-Ph] , 277 (3) [M-(p-tolyl ion)] , 263
(24) [M-PhCO] , 105 (85) [PhCO] , 91 (100) [p-tolyl
ion] . Anal. Calcd for C25
+
+
+
(0.4 mL, 5 mmol) was added, followed by the appropriate
H N O (368.48): Calcd C
24 2
primary amine (2 mmol) and few drops of acetic acid. The
reaction mixture was heated on water bath for 3 h, then
cooled, and diluted with water (10 mL) and neutralized
with ammonium hydroxide solution. The product that
separated was filtered off and crystallized from ethanol.
81.49, H 6.57, N 7.60. Found C 81.36, H 6.49, N 7.55.
5
-Benzoyl-(1,3-bis(p-anisyl)-1,2,3,4-tetrahydropyrimidine)
(
3e). Yield 96%, (pale-green crystal), mp 161–163°C; IR
(
1
KBr): ν = 3060, 1660 (C═O), 1632 (C═C), 1548, 1472,
ꢀ
1 1
292, 1238, 1025 cm , H NMR (CDCl ): δ = 3.77 (s,
3
3
H, OCH ), 3.79 (s, 3H, OCH ), 4.44 (s, 2H, 4-H ), 5.03
5
-Benzoyl-3-benzyl-1-phenyl-1,2,3,4-tetrahydropyrimidine
3
3
2
(3a). Yield 70%, (pale-yellow powder), mp 123–125°C
(s, 2H, 2-H ), 6.80–7.55 (m-13H, Ar─H), 7.66 ppm (s,
2
3
1
(
(
122–123°C [31]); IR (KBr): ν = 3028, 2858, 2916, 1663
C═O), 1616 (C═C), 1584, 1511, 1254, 1145 cm ; H
1H, 6-H); C NMR (CDCl ): δ = 47.4 (OCH ), 55.5 (C-
3 3
ꢀ
1 1
4), 67.5 (C-2), 109.5(C-5), 114.5, 114.9, 119.8, 121.0,
128.1, 128.4, 130.1, 137.6, 139.8, 142.3, 146.9, 154.5
(all Ar─C), 157.0 (C-6), 193.0 ppm (C═O); MS (EI,
NMR (CDCl ): δ = 3.80 (s, 2H, 4-H ), 3.96 (s, 2H,
3
2
CH Ph), 4.53 (s, 2H, 2-H ), 6.91–7.64 (m, 15H, Ar─H),
2
2
1
3
+
+
7
4
1
1
.67 ppm (s, 1H, 6-H); C NMR (CDCl ): δ = 48.2 (C-
70 eV): m/z (%) = 402 (5) [M + 2] , 401 (31) [M + 1] ,
3
+
+
), 57.0 (CH ─Ph), 67.0 (C-2), 109.4 (C-5), 118.4,
24.2, 127.5, 128.2, 128.4, 128.5, 129.2, 129.7, 129.9,
400 (100) [M] , 399 (6) [M ꢀ 1] , 120 (35), 105 (34),
2
77 (99). Anal. Calcd for C25 (400.48): Calcd C
H N O
24 2 3
30.2, 139.8, 144.4 (all Ar─C), 145.1 (C-6), 193.9 ppm
74.98, H 6.04, N 7.00. Found C 74.86, H 5.89, N 6.85.
5-Benzoyl-(1-(p-tolyl)-1,2,3,4-tetrahydropyrimidine (3f).
+
(C═O); MS (EI, 70 eV): m/z (%) = 356 (4) [M + 2] ,
+
+
Yield 65%, (yellow powder), mp 139–140°C; IR (KBr):
ν = 4443 (NH), 1648 (C═O), 1600 (C═C), 1586, 1511,
3
1
55 (5) [M + 1] , 354 (3) [M] , 262 (4), 186 (4), 158 (4),
24 (5), 105 (88), 82 (9), 77 (56). Anal. Calcd for
ꢀ
1
1
1
257 cm ; H NMR (CDCl ): δ = 1.26 (s, 1H, NH),
C H N O (354.45): Calcd C 81.33, H 6.26, N 7.90.
3
2
4 22 2
2
.33 (s, 3H, CH ), 3.84 (s, 2H, 4-H ), 4.46 (s, 2H, 2-H ),
Found C 81.28, H 6.19, N 7.82.
3
2
2
5
-Benzoyl-(1,3-diphenyl)-1,2,3,4-tetrahydropyrimidine
6.83–7.66 (m,9H, Ar─H), 7.74 ppm (s, 1H, 6-H); MS
+
+
(3b). Yield 80%, (yellow powder), mp 158–160°C (160–
(EI, 70 eV): m/z (%) = 279 (4) [M + 1] , 278 (16) [M] ,
+
+
1
1
61°C [31]); IR (KBr): ν = 1638 (C═O), 1610 (C═C),
277 (11) [M ꢀ 1] , 263 (7), 235 (2), 173 (2) [M-PhCO] ,
ꢀ
1
1
+
585, 1547, 1278, 1236 cm
;
H NMR (CDCl3):
105 (100) [PhCO] , 77 (72). Anal. Calcd for C H N O
18
18 2
δ = 4.55 (s, 2H, 4-H ), 5.22 (s, 2H, 2-H ), 6.93–7.66 (m,
(278.36): Calcd C 77.67, H 6.52, N 10.06. Found C
2
2
1
5H, Ar─H), 7.73 ppm (s, 1H, 6-H); MS (EI, 70 eV): m/
77.60, H 6.46, N 9.88.
+
+
z (%) = 341(8) [M + 1] , 340 (28) [M] , 105 (90), 77
1,4-Bis(5-benzoyl-1-(-tolyl)-1,2,3,4-tetrahydropyrimidin-3-
yl)-benzene (4a).
A solution of 2b (0.47 g, 2 mmol),
formalin 37% (0.4 mL, 5 mmol), and p-phenylenediamine
0.11 g, 1 mmol) in ethanol (20 mL), and few drops of
(100). Anal. Calcd for C H N O (340.43): Calcd C
23 20 2
81.15, H 5.92, N 8.23. Found C 81.09, H 5.89, N 8.11.
(
5
-Benzoyl-3-benzyl-1-(p-tolyl)-1,2,3,4-tetrahydropyrimidine
(3c).
Yield 70%, (yellow powder), mp 90–91°C (92–
acetic acid was heated on water bath for 4 h. The separated
93°C [31]); IR (KBr): ν = 1650 (C═O), 1600 (C═C),
crystalline solid was filtered and washed with boiling
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Mannich Reaction with Enaminones
Ar─H), 7.54 ppm (s, 1H, 4-H); MS (EI, 70 eV): m/z
ethanol to give 4a. Yield 60%, (green powder), mp
+
+
+
280–282°C; IR (KBr): ν = 1671 (C═O), 1610 (C═C),
(%) = 296 (2) [M + 1] , 295 (4) [M] , 294 (1) [M ꢀ 1] ,
ꢀ
1
1
+
1586, 1563, 1511, 1258 cm ; H NMR (DMSO-d6):
293 (2) [M ꢀ 2] , 266 (17), 265 (60), 264 (100) [M-
+
δ = 2.33 (s, 6H, 2 × CH ), 4.26 [s, 4H, 2 × (4-H )], 5.18 [s,
OCH ] , 105 (53), 83 (27), 77 (23). Anal. Calcd for
3
2
3
4
2
6
H, 2 × (2-H )], 6.84–7.44 (m, 22H, Ar─H), 7.57 ppm [s,
C H NO (295.34): Calcd C 73.20, H 5.80, N 4.74.
Found C 73.10, H 5.77, N 4.68.
5-Benzoyl-1-(4-hydroxyphenyl)-3-(p-tolyl)-1,2,3,4-
2
18 17
3
+
H, 2 × (6-H)]; MS (EI, 70 eV): m/z (%) = 630 (10) [M] ,
+
+
29 (2) [M ꢀ 1] , 615 (7) [M-CH ] , 420 (24) [M-
3
+
tetrahydropyrimidine (7).
A mixture of 2d (1.91 g,
(2 × PhCO)] , 277 (49), 201 (8), 173 (4), 105 (10)
+
8 mmol), formalin 37% (1.3 mL, 16 mmol) and p-
toluidine (0.85 g, 8 mmol) in ethanol (20 mL), and few
drops of acetic acid was heated on steam bath for 4 h,
then cooled and poured on cold water (20 mL), and
neutralized with ammonium hydroxide solution. The
solid product was filtered and crystallized from ethanol to
give 7. Yield 80%, (pale-brown powder), mp 165–167°C;
IR (KBr): ν = 3224 (OH), 1645 (C═O), 1600 (C═C),
[PhCO] , 91 (40), 77 (72). Anal. Calcd for C H N O
42 38 4 2
(630.79): Calcd C 79.97, H 6.07, N 8.88. Found C 79.91,
H 5.99, N 8.79.
1
,4-Bis(5-benzoyl-1-(p-anisyl)-1,2,3,4-tetrahydropyrimidin-3-
yl)-benzene (4b). This compound was obtained from 2c
0.50 g, 2 mmol) following the same procedure as
(
described earlier for compound 4a. Yield 75%, (green
powder), mp 285–287°C; IR (KBr): ν = 1673(C═O),
ꢀ
1
1
ꢀ1
1
1630 (C═C), 1587, 1512, 1258, 1143, 716 cm
;
H
1582, 1510, 1260 cm ; H NMR (CDCl ): δ = 2.33 (s,
3
NMR (DMSO-d ): δ = 3.72 (s, 6H, 2 × OCH ), 4.24 [s,
3 H, CH ), 4.53 (s, 2H, 4-H ), 5.11 (s, 2H, 2-H ), 6.81–
6
3
3
2
2
4
2
7
H, 2 × (4-H )], 5.25 [s, 4H, 2 × (2-H )], 6.84–7.45 (m,
7.53 (m, 13H, Ar─H), 7.65 (s, 1H, 6-H), 9.12 ppm (s,
2
2
+
2H, Ar─H), 7.55 ppm [s, 2H, 2 × (6-H)]; MS (EI,
1H, OH); MS (EI, 70 eV): m/z (%) = 372 (3) [M + 2] ,
+
+
+
+
+
0 eV): m/z (%) = 663 (58) [M + 1] , 662 (4) [M] , 454
371 (11) [M + 1] , 370 (47) [M] , 369 (19) [M ꢀ 1] ,
+ +
(9), 448 (7), 369 (43), 293 (29), 105 (21), 83 (19),77
368 (46) [M ꢀ 2] , 105 (61) [PhCO] , 91 (53) [p-tolyl
+ +
(15). Anal. Calcd for C H N O (662.79): Calcd C
ion] , 77 (100) [Ph] . Anal. Calcd for C H N O
24 22 2 2
4
2
38
4
4
7
6.11, H 5.78, N 8.45. Found C 76.08, H 5.72, N 8.40.
(370.45): Calcd C 77.81, H 5.99, N 7.56; Found C 77.78,
H 5.95, N 7.50.
1
,2-Bis(5-benzoyl-1-phenyl-1,2,3,4-tetrahydropyrimidin-3-
yl)-ethane (5).
This compound was obtained from 2a
Synthesis of the phenolic Mannich bases 8a–c.
A
(0.44 g, 2 mmol), ethylenediamine (0.1 mL, 1 mmol) and
mixture of
hydrochloride (0.12 g, 1.5 mmol) or piperidine (0.15 mL,
.5 mmol) or morpholine (0.13 mL, 1.5 mmol) and
7 (0.37 g, 1 mmol), dimethylamine
formalin 37% (0.4 mL, 5 mmol), following the same
procedure as described earlier for compound 4a. Yield
1
8
2
1
3
6
5%, (white powder), mp 220–222°C; IR (KBr): ν = 2852,
formalin 37% (0.15 mL, 1.5 mmol), and few drops of
acetic acid was refluxed for 8 h. After cooling to room
temperature, the reaction mixture was poured on cold
water (20 mL), the separated solid was filtered off and
crystallized from ethanol.
5-Benzoyl-1-(3-dimethylaminomethyl-4-hydroxyphenyl)-3-p-
tolyl-1,2,3,4-tetrahydropyrimidine (8a). Yield 65%, (pale-
952, 1660 (C═O), 1616 (C═C), 1560, 1495, 1465, 1264,
ꢀ
1 1
150 cm ; H NMR (CDCl ): δ = 2.83 (s, 4H, 2 × CH ),
.84 [s, 4H, 2 × (4-H )], 4.63 [s, 4H, 2 × (2-H )],
3
2
2
2
.91–7.55 (m, 20H, Ar─H), 7.56 ppm [s, 2H, 2 × (6-H)];
1
3
0
C NMR (CDCl ): δ = 47.5 (2 × CH ), 50.6 (C-4, C-4 ),
3
2
0
0
68.5 (C-2, C-2 ), 108.9 (C-5, C-5 ), 118.6, 124.4, 128.2,
1
28.4, 129.7, 130.2, 139.6, 144.2 (all Ar─C), 145.1 (C-6,
brown powder), mp 172–173°C; IR (KBr): ν = 3382
0
ꢀ1
C-6 ), 193.9 ppm (C═O); MS (EI, 70 eV): m/z (%) = 554
(OH), 1661 (C═O), 1583, 1510, 1384, 1258, 1072 cm
;
+
+
+
1
(
[
4) [M] , 477 (17) [M-Ph] , 400 (18) [M-2 Ph] , 344 (13)
M-2 PhCO] , 291 (12), 158 (12), 81 (8). Anal. Calcd for
H NMR (CDCl ): δ = 2.25 (s, 6H, N (CH ) ), 2.33 (s,
3 3 2
+
3
H, CH ), 3.72 (s, 2H, CH N), 4.43 (s, 2H, 4-H ), 5.07
3 2 2
C H N O (554.69): Calcd C 77.95, H 6.18, N 10.10.
Found C 77.89, H 6.10, N 9.97.
(s, 2H, 2-H ), 6.80–7.58 (m, 12H, Ar─H), 7.66 (s,1H, 6-
3
6 34 4 2
2
H), 9.03 ppm (s, 1H, OH); MS (EI, 70 eV): m/z
5
-Benzoyl-3-(p-anisyl)-3,6-dihydro-2H-1,3-oxazine (6).
A
+
+
(
[
%) = 429 (1) [M + 2] , 428 (5) [M + 1] , 427 (15)
solution of 2c (0.25 g, 1 mmol), formalin 37% (0.4 mL,
mmol) in ethanol (20 mL), and few drops of acetic acid
+
+
M] , 368 (100) [M-CH N(CH ) ] , 105 (12), 91 (8), 77
2 3 2
5
(
7). Anal. Calcd for C H N O (427.55): Calcd C
27 29 3 2
was heated for 2 h on steam bath, left to stand at room
temperature overnight, diluted with water (20 mL), and
basified with ammonium hydroxide solution. The
precipitated product was filtered off and dried.
Crystallization from ethanol gave 6. Yield 60%, (yellow
powder), mp 145–146°C; IR (KBr): ν = 3054, 2931,
7
5.85, H 6.84, N 9.83. Found C 75.78, H 6.80, N 9.78.
5-Benzoyl-1-(3-piperidin-1-ylmethyl-4-hydroxyphenyl)-3-p-
tolyl-1,2,3,4-tetrahydropyrimidine (8b). Yield 60%, (pale-
brown powder), mp 177–178°C; IR (KBr): ν = 3472
(OH), 1663 (C═O), 1586, 1512, 1382, 1257 cm
NMR (CDCl ): δ = 1.72–1.81 (m, 6H, 3-H , 4-H , 5-H )
ꢀ
1 1
;
H
3
2
2
2
1
1
4
647 (C═O), 1610 (C═C), 1587, 1509, 1244, 1175,
of piperidine), 2.34 (s, 3H, CH ), 2.52 (m, 4H, 2-H 6-
3 2,
ꢀ
1 1
032 cm ; H NMR (CDCl ): δ = 3.82 (s, 3H, OCH ),
H of piperidine), 3.63 (s, 2H, Ar─CH ─N), 4.46 (s, 2H,
3
3
2
2
.43 (s, 2H, 6-H ), 5.01 (s, 2H, 2-H ), 6.80–7.53 (m, 9H,
4-H ), 5.08 (s, 2H, 2-H ), 6.81–7.50 (m, 12H, Ar─H),
2
2
2
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

E. M. Afsah, E.-S. I. El-Desoky, H. A. Etman, I. Youssef, and A. M. Soliman
Vol 000
+
7
.63 (s, 1H, 6-H), 9.61 ppm (s, 1H, OH); MS (EI, 70 eV):
piperidinomethyl ion] , 105 (74), 91 (18), 83 (51). Anal.
+
+
m/z (%) = 468 (33) [M + 1] , 467 (43) [M] , 466 (13)
Calcd for C H N O (564.77): Calcd C 76.56, H 7.85,
3
6 44 4 2
+
+
[
M ꢀ 1] , 382 (56) [M-C H N] , 376 (25) [M-(p-tolyl
N 9.92. Found C 76.48, H 7.80, N 9.89.
5-Benzoyl-(1-(3,5-bis(morpholinomethyl))-4-
hydroxyphenyl)-3-p-tolyl-1,2,3,4-tetrahydro-pyrimidine (9c).
Yield 80%, (brown powder), mp 188–189°C; IR (KBr):
ν = 3220 (OH), 1640 (C═O), 1590, 1520, 1456, 1390,
5
10
+
+
ion)] , 369 (4) [M-piperidinomethyl ion] , 362 (2) [M-
+
PhCO] , 277 (21), 190 (52), 98 (12), 81 (21). Anal.
Calcd for C H N O (467.61): Calcd C 77.06, H 7.11,
N 8.99. Found C 76.93, H 6.98, N 8.88.
30 33 3 2
ꢀ
1 1
5
-Benzoyl-1-(3-morpholinomethyl-4-hydroxyphenyl)-3-p-
1259, 1145 cm ; H NMR (CDCl
): δ = 2.36 (s, 3H,
3
tolyl-1,2,3,4-tetrahydropyrimidine (8c). Yield 70%, (brown
CH ), 2.65 [m, 8H, 2 × (CH ─N─CH ) of morpholine],
3
2
2
powder), mp 179–180°C; IR (KBr): ν = 3246 (OH), 1663
3.64 [s, 4H, 2 × (Ar─CH ─N)], 3.92 [m, 8H,
2
ꢀ
1 1
(C═O), 1584, 1511, 1451, 1385, 1259, 1116 cm ; H
2 × (CH ─O─CH ) of morpholine], 4.46 (s, 2H, 4-H ),
2
2
2
NMR (CDCl ): δ = 2.31 (s, 3H, CH ), 2.63 (m, 4H,
5.14 (s, 2H, 2-H ), 6.81–7.52 (m,11H, Ar─H), 7.53 (s,
3
3
2
CH ─N─CH2 of morpholine), 3.55 (m, 4H,
1H, 6-H), 9.54 ppm (s, 1H, OH); MS (EI, 70 eV): m/z
2
+
+
CH ─O─CH2 of morpholine), 3.74 (s, 2H,
(%) = 568 (86) [M] , 567 (18) [M ꢀ 1] , 566 (36)
2
+ +
Ar─CH ─N), 4.45 (s, 2H, 4-H ), 5.07 (s, 2H, 2-H ),
[M ꢀ 2] , 480 (19) [M-morpholine ion] , 476 (6) [M-(p-
+ +
2
2
2
6.81–7.50 (m, 12H, Ar─H), 7.57 (s, 1H, 6-H), 9.71 ppm
tolyl ion)] , 463 (21) [M-morpholinomethyl ion] , 396
+
(
[
3
s, 1H, OH); MS (EI, 70 eV): m/z (%) = 471 (21)
(31) [M-2 morpholine ion] , 301 (100), 104 (93), 92
+
+
+
M + 2] , 470 (51) [M + 1] , 469 (10) [M] , 451 (33),
(81), 81 (21), 77 (49). Anal. Calcd for C H N O
34 40 4 4
+
93 (12) [M-Ph] , 384 (15), 376 (7), 369 (12) [M-
(568.72): Calcd C 71.81, H 7.09, N 9.85. Found C 71.79,
H 7.04, N 9.78.
+
+
morpholinomethyl ion] , 364 (7) [M-PhCO] , 277 (28),
04 (52), 91 (51), 77 (45). Anal. Calcd for C H N O
9 31 3 3
1
,3-(Bis(4-hydroxyphenyl))-5-benzoyl-1,2,3,4-
1
2
tetrahydropyrimidine (10).
A mixture of 2d (1.20 g,
(469.59): Calcd C 74.18, H 6.65, N 8.95. Found C 74.10,
5
mmol), formalin 37% (0.8 mL, 10 mmol) and p-
H 6.57, N 8.86.
aminophenol (0.54 g, 5 mmol) in ethanol (20 mL), and
few drops of acetic acid was heated on steam bath for
Synthesis of the phenolic Mannich bases 9a–c. These
compounds were obtained from 7 (0.37 g, 1 mmol), the
appropriate sec-amine (2.5 mmol) and formalin 37%
4
h, then cooled and poured on cold water (10 mL), and
neutralized by ammonium hydroxide solution. The solid
product was filtered off and crystallized from ethanol to
give 10. Yield 85%, (brown powder), mp 184–185°C; IR
(KBr): ν = 3230 (OH), 1652 (C═O), 1583, 1550, 1510,
(2.5 mmol, 0.2 mL), following the same procedure as
described earlier for compounds 8a–c.
5
-Benzoyl-(1-(3,5-bis(dimethylaminomethyl))-4-
hydroxyphenyl)-3-p-tolyl-1,2,3,4-tetrahydro-pyrimidine (9a).
Yield (66%), (brown powder), mp 175–176°C; IR (KBr):
ν = 3217 (OH), 1659 (C═O), 1588, 1514, 1455, 1386,
ꢀ
1 1
1
388, 1260 cm ; H NMR (CDCl ): δ = 4.22 (s, 2H, 4-
3
H
), 5.04 (s, 2H, 2-H
2
), 6.72–7.44 (m, 13H, Ar─H), 7.57
2
ꢀ
1 1
1
260, 1146 cm ; H NMR (CDCl ): δ = 2.23 [s, 6H, N
(s, 1H, 6-H), 9.74 ppm (s, 2H, 2 × OH); MS (EI, 70 eV):
3
+
+
m/z (%) = 374 (1) [M + 2] , 373 (2) [M + 1] , 372 (9)
(
CH ) ], 2.33 (s, 3H, CH ), 2.45 [s, 6H, N (CH ) ], 3.71
3 2 3 3 2
+
+
+
[
s, 4H, 2 × (CH ─N) (Me) ], 4.43 (s, 2H, 4-H ), 5.06 (s,
[M] , 371 (4) [M ꢀ 1] , 295 (3) [M-Ph] , 279 (10), 267
2
2
2
+
2
H, 2-H ), 6.82–7.56 (m, 11H, Ar─H), 7.66 (s, 1H, 6-
(11) [M-PhCO] , 105 (55), 81 (20), 77 (100). Anal.
2
Calcd for C H N O (372.42): Calcd C 74.18, H 5.41,
H), 9.46 ppm (s, 1H, OH); MS (EI, 70 eV): m/z
23 20 2 3
+
+
+
(
3
(
%) = 486 (1) [M + 2] , 485 (3) [M + 1] , 484 (2) [M] ,
N 7.52. Found C 74.10, H 5.38, N 7.48.
+
+
93 (4) [M-(p-tolyl ion)] , 379 (100) [M-PhCO] , 378
Synthesis of the tetra (Mannich bases) 11a and 11b.
A
+
98), 368 (2) [M-2(CH NMe )] , 105 (14), 77 (9). Anal.
mixture of 10 (0.37 g, 1 mmol), formalin 37% (0.4 mL,
5 mmol), piperidine (0.5 mL, 5 mmol) or morpholine
(0.4 mL, 5 mmol) in ethanol (20 mL), and few drops of
acetic acid was heated under reflux for 10 h, then cooled
and poured on cold water (20 mL), and neutralized by
ammonium hydroxide solution. The solid product was
2
2
Calcd for C H N O (484.64): Calcd C 74.35, H 7.49,
30 36 4 3
N 11.56. Found C 74.29, H 7.42, N 11.48.
5
-Benzoyl-(1-(3,5-bis(piperidin-1-ylmethyl))-4-
hydroxyphenyl)-3-p-tolyl-1,2,3,4-tetrahydro-pyrimidine (9b).
Yield 70%, (pale-brown powder), 181–183°C; IR (KBr):
ν = 3500 (OH), 1660 (C═O), 1586, 1512, 1382, 1257,
filtered off and crystallized from ethanol.
5-Benzoyl-(1,3-bis(4-hydroxy-3,5-bis(piperidin-1-ylmethyl))
ꢀ
1 1
1
2
2
2
144 cm ; H NMR (CDCl ): δ = 1.73–1.82 [m, 12H,
3
× (3-H , 4-H , 5-H ) of piperidine], 2.33 (s, 3H, CH ),
phenyl)-1,2,3,4-tetrahydro-pyrimidine (11a).
Yield 55%,
2
2
2
3
.65 [m, 8H, 2 × (2-H , 6-H ) of piperidine], 3.73 [s, 4H,
× (Ar─CH ─N)], 4.22 (s, 2H, 4-H ), 5.34 (s, 2H, 2-
(brown powder), mp 192–193°C; IR (KBr): ν = 3469
2
2
ꢀ
1
(OH), 2933, 1666 (C═O), 1585, 1472, 1386, 1256 cm ;
2
2
1
H ), 6.72–7.53 (m, 11H, Ar─H), 7.74 (s, 1H, 6-H),
2
H NMR (CDCl ): δ = 1.61 [m, 8H, 4 × (4-H ) of
3
2
9
.49 ppm (s, 1H, OH); MS (EI, 70 eV): m/z (%) = 565
piperidine], 1.73 [m, 16H, 4 × (3-H , 5-H ) of
2 2
piperidine], 2.72 [m, 16H, 4 × (2-H , 6-H ) of
2 2
+
+
+
(
[
2) [M + 1] , 564 (5) [M] , 563 (3) [M ꢀ 1] , 481 (3)
+
+
M-C H N] , 473 (7) [M-(p-tolyl ion)] , 467 (100) [M-
piperidine], 3.74 [s, 8H, 4 × (Ar─CH ─N)], 4.33 (s, 2H,
5
10
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Mannich Reaction with Enaminones
+
+
4
-H ), 5.02 (s, 2H, 2-H ), 6.72–7.53 (m, 9H, Ar─H), 7.64
(100) [M-CH Ph] , 77 (31) [Ph] . Anal. Calcd for
2
2
2
(
s, 1H, 6-H), 7.99 ppm (br s, 2H, 2 × OH); MS (EI, 70 eV):
C H N O (630.79): Calcd C 79.97, H 6.07, N 8.88.
Found: C 79.91, H 6.00, N 8.79.
1,4-Bis(5-benzoyl-3-(p-tolyl)-1,2,3,4-tetrahydropyrimidin-1-
yl)-benzene (13b). Yield 75%, (brown powder), mp 229–
42 38 4 2
+
+
m/z (%) = 761 (2) [M + 1] , 760 (9) [M] , 662 (4) [M-
piperidinomethyl ion] , 564 (3), 367 (21) [M-
+
+
(4 × piperidinomethyl ion)] , 287 (42), 105 (39), 77 (80).
2
1
30°C; IR (KBr): ν = 3053, 2918, 1649 (C═O), 1585,
Anal. Calcd for C H N O (760.07): Calcd C 74.17, H
8
4
7 64 6 3
ꢀ
1
1
560, 1511, 1384, 1256 cm ; H NMR (DMSO-d ):
.48, N 11.04. Found C 74.11, H 8.39, N 10.96.
6
5
-Benzoyl-(1,3-bis(4-hydroxy-3,5-bis(morpholinomethyl)))
δ = 2.31 (s, 6H, 2 × CH ), 4.33 [s, 4H, 2 × (4-H )], 5.24
3 2
phenyl)-1,2,3,4-tetrahydro-pyrimidine (11b).
Yield 65%,
[s, 4H, 2 × (2-H )], 6.81–7.58 (m, 22H, Ar─H),
2
(
(
brown powder), mp 195–197°C; IR (KBr): ν = 3471
OH), 1665 (C═O), 1584, 1496, 1390, 1257 cm ; H
7.66 ppm [br s, 2H, 2 × (6-H)]; MS (EI, 70 eV m/z
ꢀ
1
1
+
+
(%) = 631(2) [M + 1] , 630 (14) [M] , 600 (6), 448
+
NMR (CDCl ): δ = 2.55 [m, 16H, 4 × (CH ─N─CH ) of
(18) [M-2 p-tolyl ions] , 353 (35), 277 (8), 105 (12),
3
2
2
morpholine], 3.72 [s, 8H, 4 × (Ar─CH ─N)], 3.8 [m,
81(4), 77(16). Anal. Calcd for C H N O (630.79):
Calcd C 79.97, H 6.07, N 8.88. Found C 79.90, H 5.94,
2
42 38 4 2
1
6H, 4 × (CH ─O─CH ) of morpholine], 4.33 (s, 2H, 4-
2
2
H ), 5.01 (s, 2H, 2-H ), 6.66–7.57 (m, 9H, Ar─H), 7.61
N 8.79.
2
2
(
7
s, 1H, 6-H), 8.01 ppm (br s, 2H, 2 × OH); MS (EI,
1,4-Bis(5-benzoyl-3-(p-anisyl)-1,2,3,4-tetrahydropyrimidin-1-
yl)-benzene (13c). Yield 70%, (pale-green powder), mp
240–242°C; IR (KBr): ν = 1640 (C═O), 1613 (C═C),
1585, 1559, 1511, 1249 cm ; H NMR (DMSO-d ):
δ = 3.62 [(s, 6H, 2 × OCH ), 4.24 [s, 4H, 2 × (4-H )],
+
+
0 eV): m/z (%) = 770 (27) [M + 2] , 768 (42) [M] , 680
+
(29), 668 (7) [M-morpholinomethyl ion] , 596 (10) [M-2
ꢀ
1
1
+
+
morpholine ions] , 424 (21) [M-4 morpholine ions] , 105
18), 91 (100), 80 (6), 77 (61). Anal. Calcd for
C H N O (768.96): Calcd C 67.17, H 7.34, N 10.93.
6
(
3
2
5
.13 [s, 4H, 2 × (2-H )], 6.71–7.55 (m, 22H, Ar─H),
2
4
3 56 6 7
7
.57 ppm [br s, 2H, 2 × (6-H)]; MS (EI, 70 eV): m/
Found C 67.10, H 7.29, N 10.87.
0
+
+
N,N -(bis-(1-phenylprop-2-en-1-one-3-yl))-p-phenylenediamine
z = 663(3) [M + 1] , 662 (20) [M] , 449 (13), 368 (48),
344 (100), 104 (26), 76 (63). Anal. Calcd for
C H N O4 (662.79): Calcd C 76.11, H 5.78, N 8.45.
(12).
A mixture of 1 (3.51 g, 2 mmol) and p-
phenylenediamine (1.08 g, 1 mmol) in dioxane (20 mL)
was heated under reflux for 6 h, the crystalline product that
obtained on heating was filtered, washed by boiling ethanol
to give 12. Yield 83%, (green powder), mp 200–201°C; IR
42 38 4
Found C 76.05, H 5.71, N 8.39.
1,4-Bis(5-benzoyl-3-(pyridin-4-yl)-1,2,3,4-tetrahydropyrimidin-
1-yl)-benzene (13d). Yield 65%, (green powder), mp 218–
(
1
2
3
KBr): ν = 3447 (NH), 1660 (C═O), 1633 (C═C), 1531,
220°C; IR (KBr): ν = 1665 (C═O), 1621 (C═C), 1512,
ꢀ
1
1
ꢀ1
1
467, 1269 cm ; H NMR (DMSO-d ): δ = 6.11 (d, 2H,
1443, 1238 cm ; H NMR (DMSO-d
2 × (4-H )], 5.35 [s, 4H, 2 × (2-H )], 7.61 [s, 2H, 2 × (6-
H)], 6.81–8.61 ppm (m, 22H, Ar─H); MS (EI, 70 eV): m/z
): δ = 4.33 [s, 4H,
6
6
0
-H, 2 -H), 7.37–7.95 (m, 14H, Ar─H), 7.96 (d, 2H, 3-H,
-H), 12.21 ppm (d, 2H, 2 × NH); MS (EI, 70 eV): m/z
2
2
0
+
+
+
+
+
(%) = 370 (4) [M + 2] , 369 (23) [M + 1] , 368 (100)
(%) = 604 (22) [M] , 603 (6) [M ꢀ 1] , 602 (4) [M ꢀ 2] ,
+
+
+ +
[
M] , 367 (60) [M ꢀ 1] , 158 (50), 105 (37), 77 (61). Anal.
601(15) [M ꢀ 3] , 450 (14) [M–2 Ph] , 392 (39) [M–
+
Calcd for C H N O (368.44): Calcd C 78.24, H 5.47, N
(2 × PhCO)] . Anal. Calcd for C38H N O (604.71): Calcd
32 6 2
24 20 2 2
7
.60. Found C 78.20, H 5.40, N 7.55.
Synthesis of bis(tetrahydropyrimidines) 13a–f.
C 75.48, H 5.33, N 13.90. Found C 75.41, H 5.28, N 13.81.
1,4-Bis(5-benzoyl-3-(4-hydroxyphenyl)-1,2,3,4-tetrahydropyrimidin-
A
1-yl)-benzene (13e). Yield 67%, (brown powder), mp 225–
mixture of 12 (0.37 g, 1 mmol), formalin 37% (5 mL,
mmol), the appropriate primary amine (2 mmol), and
2
26°C; IR (KBr): ν = 3455 (OH), 1649 (C═O), 1585, 1564,
5
ꢀ
1 1
1512, 1449 cm ; H NMR (DMSO-d ): δ = 4.13 [s, 4H,
few drops of acetic acid in ethanol-DMF (1:3) (20 mL)
was heated under reflux for 5 h. Then left to cool and
poured on cold water (20 mL), the solid product was
filtered, dried, and crystallized from ethanol-DMF (1:3)
to give compounds 13a–f.
6
2
× (4-H )], 4.99 [s, 4H, 2 × (2-H )], 6.51–7.42 (m, 22H,
2 2
Ar─H), 7,51 [br s, 2H, 2 × (6-H)], 8.93 ppm (br s, 2H,
+
2
5
× OH); MS (EI, 70 eV): m/z (%) = 634 (25) [M] , 600 (16),
+
+
56 (8) [M-Ph] , 424 (11) [M–(2 × PhCO)] , 355 (15),
1
,4-Bis(5-benzoyl-3-benzyl-1,2,3,4-tetrahydropyrimidin-1-
81(15). Anal. Calcd for C H N O (634.74): Calcd C 75.69,
40 34 4 4
yl)-benzene (13a). Yield 70%, (deep-green powder), mp
H 5.40, N 8.83. Found C 75.63, H 5.37, N 8.78.
1,4-Bis(5-benzoyl-3-phenyl-1,2,3,4-tetrahydropyrimidin-1-
yl)-benzene (13f). Yield 55%, (brown powder), mp 210–
253–255°C; IR (KBr) ν = 3199, 2924, 1665 (C═O),
ꢀ
1 1
1
586, 1556, 1495, 1442, 1284 cm ; H NMR (DMSO-
d ): δ = 3.62 [s, 4H, 2 × (4-H )], 3.73 [s, 4H,
212°C; IR (KBr): ν = 1639 (C═O), 1600 (C═C), 1550,
6
2
ꢀ
1 1
2
2
× (CH Ph)], 4.53 [s, 4H, 2 × (2-H )], 7.05–7.54 (m,
6H, Ar─H), 7.72 ppm [br s, 2H, 2 × (6-H)]; C NMR
1507, 1474, 1293 cm ; H NMR (DMSO-d
[s, 4H, 2 × (4-H )], 5.24 [s, 4H, 2 × (2-H )], 6.81–7.63
(m, 24H, Ar─H), 7.76 ppm [br s, 2H, 2 × (6-H)]; MS
6
): δ = 4.43
2
2
1
3
2
2
(
DMSO-d ): δ = 47.0 (C-4), 56.3 (CH Ph)), 67.6 (C-2),
6
2
+
+
1
1
08.4 (C-5, C-`5), 120.1, 127.6, 128.6, 128.7, 129.2,
(EI, 70 eV): m/z (%) = 602 (12) [M] , 525 (8) [M-Ph] ,
+
30.5 (all Ar─C), 145.1 (C-6, C-`6), 192.6 ppm (C═O);
392 (100) [M–(2 × PhCO)] , 339 (12), 296 (7), 265 (7),
186 (9), 105 (30) [PhCO] , 77 (20). Anal. Calcd for
+
+
MS (EI, 70 eV): m/z (%) = 630 (4) [M] , 277 (34), 91
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

E. M. Afsah, E.-S. I. El-Desoky, H. A. Etman, I. Youssef, and A. M. Soliman
Vol 000
+
+
C H N O (602.74): Calcd C 79.71, H 5.69, N 9.30.
70 eV): m/z (%) = 614 (6) [M] , 460 (3) [M-2 Ph] , 404
4
0 34 4 2
+
Found C 79.69, H 5.60, N 9.19.
(5) [M–(2 × PhCO)] , 400 (100) [M–2 × (p-anizyl
ions)] , 307 (8), 104 (51), 81 (6), 77 (28). Anal. Calcd
for C H N O (614.75): Calcd C 74.24, H 6.23, N
.11. Found C 74.20, H 6.18, N 8.96.
1,2-Bis(5-benzoyl-1,2,3,4-tetrahydropyrimidin-1-yl)-ethane
+
1
,4-Bis(5-benzoyl-3,6-dihydro-2H-1,3-oxazine-3-yl)-benzene
14). A mixture of 12 (0.36 g, 1 mmol), formalin 37%
0.5 mL, 5 mmol) in ethanol-DMF (1:3) (20 mL), and
(
(
38 38 4 4
9
few drops of acetic acid was heated under reflux for 4 h,
the crystalline product that obtained on heating was
filtered off, washed by boiling ethanol to give 14. Yield
(16d).
Yield 72%, (deep-yellow powder), mp
178–179°C; IR (KBr): ν = 3428 (NH), 2925, 1665 (C═O),
ꢀ
1
1
55%, (green powder), mp > 300°C; IR (KBr): ν = 1648
1600 (C═C), 1552, 1442 cm ; H NMR (DMSO-d ):
6
(
1
4
C═O), 1625 (C═C), 1587, 1554, 1508, 1384,
δ = 1.03 (br s, 2H, 2 × NH), 3.63 (br s, 4H, 2 × CH2),
ꢀ
1
+
273 cm ; MS (EI, 70 eV): m/z (%) = 453 (2) [M + 1] ,
4.00 [s, 4H, 2 × (4-H )], 4.56 [s, 4H, 2 × (2-H )],
2
2
+
+
52 (11) [M] , 451 (2) [M-1] , 364 (10), 105 (16), 83 (2)
6.90–7.53 (m, 10H, Ar─H), 7.92 ppm [br s, 2H,
+
+
[C H NO] , 77 (11). Anal. Calcd for C H N O
2 × (6-H)]; MS (EI, 70 eV): m/z (%) = 402 (12) [M] , 359
4
5
28 24 2 4
+
+
(452.51): Calcd C 74.32, H 5.35, N 6.19. Found C 74.29,
(100), 325 (19) [M-Ph] , 249 (13) [M-2Ph] , 214 (13), 97
H 5.30, N 6.11.
(18), 82 (10), 77 (16). Anal. Calcd for C H N O
2
4 26 4 2
Synthesis of bis(tetrahydropyrimidines) 16a–d.
To a
(402.50): Calcd C 71.62, H 6.51, N 13.92. Found C
71.58, H 6.49, N 13.88.
solution of 15 [51] (0.32 g, 1 mmol) in ethanol (20 mL),
formalin 37% (0.4 mL, 5 mmol), and the appropriate
primary amine (2 mmol) were added followed by few
drops of acetic acid. The reaction mixture was heated on
a water bath for 5 h, then cooled, poured on cold water
10 mL), and neutralized with ammonium hydroxide
solution. The solid product filtered off, dried, and
crystallized from ethanol to give compounds 16a–d.
1
,2-Bis(5-benzoyl-3,6-dihydro-2H-1,3-oxazine-3-yl)-ethane
17). A mixture of 15 (0.32 g, 1 mmol) and formalin 37%
0.4 mL, 5 mmol) in ethanol (20 mL) and few drops of
(
(
acetic acid was heated on water bath for 4 h, then cooled
and poured on cold water (20 mL), and neutralized with
ammonium hydroxide solution. The product filtered off
and crystallized from ethanol to give (17). Yield 64%,
(
(yellow powder), mp 230–231°C; IR (KBr): ν = 3057,
1
,2-Bis(5-benzoyl-3-benzyl)-1,2,3,4-tetrahydropyrimidin-1-
yl)-ethane (16a).
Yield 70%, (white crystal), mp 220–
2929, 1671 (C═O), 1624 (C═C), 1557, 1442,
ꢀ
1
1
222°C; IR (KBr): ν = 3026, 2964, 1655 (C═O), 1620
1380 cm
2 × CH
2 × (2-H
2H, 2 × (4-H)]; MS (EI, 70 eV): m/z (%) = 405 (1)
;
H NMR (CDCl
), 4.34 [s, 4H, 2 × (6-H
)], 7.24–7.75 (m, 10H, Ar─H), 7.83 ppm [br s,
3
): δ = 3.51 (s, 4H,
ꢀ
1 1
(C═C), 1581, 1554, 1413 cm ; H NMR (DMSO-d ):
2
2
)], 5.10 [s, 4H,
6
δ = 3.21 (s, 4H, 2 × CH ), 3.43 [s, 4H, 2 × (4-H )], 3.61
2
2
2
[s, 4H, 2 × (CH Ph)], 3.97 [s, 4H, 2 × (2-H )], 7.14–7.35
2 2
+
+
+
(m, 20H, Ar─H), 7.44 ppm [br s, 2H, 2 × (6-H)]; MS
[M + 1] , 404 (4) [M] , 327 (18) [M-Ph] , 316 (12),
+
+
+
(EI, 70 eV): m/z (%) = 584 (2) [M + 2] , 582 (4) [M] ,
299 (9) [M-PhCO] , 105 (79), 83 (15), 77 (98). Anal.
+
+
4
77 (13) [M-PhCO] , 428 (7) [M–2 Ph] , 400 (14) [M–
Calcd for C24H N O (404.47): Calcd C 71.27, H 5.98,
24 2 4
+
(2 × CH Ph)] , 371 (59), 77 (12). Anal. Calcd for
N 6.93. Found C 71.21, H 5.91, N 6.88.
2
C H N O (582.75): Calcd C 78.32, H 6.57, N 9.61.
Found C 78.29, H 6.49, N 9.57.
Synthesis of the bis-enaminones 19a,b. A mixture of 18
[52] (2.72 g, 10 mmol) and p-toluidine (2.14 g, 20 mmol)
or 2-aminopyridine (1.88 g, 20 mmol) in DMF (20 mL)
was refluxed for 6 h, then cooled and poured on cold
water (20 mL). The product was filtered off and
crystallized from ethanol-DMF (1:2) to give compounds
19a and 19b, respectively.
3
8 38 4 2
1
,2-Bis(5-benzoyl-3-(p-tolyl)-1,2,3,4-tetrahydropyrimidin-1-
yl)-ethane (16b). Yield 67%, (pale-yellow powder), mp
1
1
70–171°C (ethanol); IR (KBr): ν = 3026, 2919, 2859,
669 (C═O), 1619 (C═C), 1584, 1559, 1512 cm ; H
ꢀ
1 1
NMR (CDCl ): δ = 2.33 (s, 6H, 2 × CH ), 3.06 [s, 4H,
3
3
0
2
× (CH )], 4.44 [s, 4H, 2 × (4-H )], 5.09 [s, 4H, 2 × (2-
1,1 -(1,4-Phenylene)bis(3-(p-tolylamino)prop-2-en-1-one
2
2
H )], 6.81–7.33 (m, 18H, Ar─H), 7.57 ppm [s, 2H,
(19a). Yield 70%, (orange powder), mp 220–222°C; IR
2
+
2
5
(
× (6-H)]; MS (EI, 70 eV): m/z (%) = 583 (1) [M + 1] ,
82 (2) [M] , 477 (2) [M-PhCO] , 428 (2) [M-Ph] , 372
3) [M–(2 × PhCO)] , 358 (100), 105 (11), 91 (14), 77
(KBr): ν = 3448 (NH), 1676 (C═O), 1634 (C═C), 1545,
+
+
+
ꢀ1
1
1485, 1427, 1275, 1057 cm ; H NMR (DMSO-d
):
6
+
δ = 2.33 (s, 6H, 2 × CH ), 6.50 [d,2H, 2 × (2-H)], 7.71
3
(
7
11). Anal. Calcd for C H N O (582.57): Calcd C
[d, 2H, 2 × (3-H)], 7.33–8.24 (m, 12H, Ar─H),
11.73 ppm (s, 2H, 2 × NH); MS (EI, 70 eV): m/z
3
8 38 4 2
8.32, H 6.57, N 9.61. Found C 78.29, H 6.54, N 9.58.
+
+
1
,2-Bis(5-benzoyl-3-(p-anisyl)-1,2,3,4-tetrahydropyrimidin-1-
(
[
[
%) = 398 (17) [M + 2] , 397 (40) [M + 1] , 396 (44)
yl)-ethane (16c). Yield 75%, (green powder), mp 175–
1
1
+
+
+
M] , 395 (22) [M ꢀ 1] , 394 (21) [M ꢀ 2] , 305 (12)
76°C; IR (KBr): ν = 2928, 1660 (C═O), 1626 (C═C),
+
M–(p-tolyl ion)] , 291 (12). Anal. Calcd for
ꢀ
1 1
557, 1510, 1245 cm ; H NMR (DMSO-d ): δ = 3.62
6
C H N O (396.49): Calcd C 78.76, H 6.10, N 7.07.
26 24 2 2
(s, 4H, 2 × CH ), 3.94 (s, 6H, 2 × OCH ), 4.45 [s, 4H,
2 3
Found C 78.72, H 5.96, N 6.98.
0
2
1
× (4-H )], 5.00 [s, 4H, 2 × (2-H )], 6.731–7.46 (m,
1,1 -(1,4-Phenylene)bis(3-(pyridin-2-ylamino)prop-2-en-1-
2
2
8H, Ar─H), 7.56 ppm [br s, 2H, 2 × (6-H)]; MS (EI,
one) (19b). Yield 60%, (yellow powder), mp 190–191°C;
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2018
Mannich Reaction with Enaminones
+
+
+
IR (KBr): ν = 3448 (NH), 1650 (C═O), 1633 (C═C), 1549,
(2) [M + 2] , 453 (3) [M + 1] , 452 (9) [M] , 291 (25), 160
ꢀ
1 1
1
474, 1421, 1236 cm ; H NMR (DMSO-d ): δ = 6.80 [d,
(3), 133 (15), 83(20), 77 (24). Anal. Calcd for C H N O
6
26 24 6 2
2
H, 2 × (2-H)], 7.91 [d, 2H, 2 × (3-H)], 6.61–8.43 (m, 12H,
(452.52): Calcd C 69.01, H 5.35, N 18.57. Found C 68.91,
H 5.25, N 17.49.
Ar─H), 12.51 ppm (s, 2H, 2 × NH); MS (EI, 70 eV): m/z
%) = 370 (100), 292 (21), 277 (63), 105 (25), 79 (20),
1
,4-Phenylenebis((3-(p-tolyl)-3,6-dihydro-2H-1,3-oxazin-5-
(
yl)methanone) (22). To a solution of 19a (0.39 g, 1 mmol)
in DMF (20 mL), formalin 37% (0.4 mL, 5 mmol) and
acetic acid (1 mL) were added. The reaction mixture
heated under reflux for 6 h. The crystalline solid that
separated during the reaction period filtered off, dried,
and washed with boiling ethanol. Yield 52%, (yellow
powder), mp 280–282°C; IR (KBr): ν = 1668 (C═O),
5
7
1 (60). Anal. Calcd for C H N O (370.41): Calcd C
22 18 4 2
1.34, H 4.90, N 15.13. Found C 71.30, H 4.88, N 15.87.
To a
solution of 19a (0.39 g, 1 mmol) or 19b (0.37 g,
Synthesis of bis(tetrahydropyrimidines) 20a,b.
1
3
mmol) in DMF (20 mL), there was added formalin
7% (0.4 mL, 5 mmol) and p-toluidine (0.11 g, 1 mmol)
or 2-aminopyridine (0.10 g, 1 mmol) followed by few
drops of acetic acid. The reaction mixture heated under
reflux for 5 h. A crystalline solid separated during the
reaction period, and it was filtered off, dried, and washed
with boiling ethanol to give compounds 20a and 20b,
respectively.
ꢀ
1
1
7
619 (C═C) 1567, 1510, 1390, 1232 cm ; MS (EI,
0 eV): m/z (%) = 480 (31) [M] , 436 (27), 392 (4), 361
+
(77), 298 (10), 278 (9), 175 (13), 134 (5), 75 (9). Anal.
Calcd for C H N O (480.56): Calcd C 74.98, H 5.87,
30 28
2 4
N 5.83. Found C 74.90, H 5.82, N 5.77.
7-Phenyl-4-(p-tolyl)-3,4-dihydro-2H-1,2,4-triazepine (23a).
A
1
,4-Phenylenebis((1,3-di-p-tolyl-1,2,3,4-tetrahydropyrimidin-
5
-l)methanone) (20a).
Yield 67%, (yellow powder),
solution of 2b (0.47 g, 2 mmol) and hydrazine hydrate (0.1 g,
mp > 300°C; IR (KBr): ν = 1666 (C═O), 1626 (C═C),
2 mmol) in ethanol (20 mL) was heated on steam bath for
ꢀ
1
30 min, then formalin 37% (0.1 mL, 1.5 mmol) and acetic
1
569, 1512, 1232 cm ; MS (EI, 70 eV): m/z (%) = 658
+
+
(
5) [M] , 642 (1) [M-CH ] , 476 (4), 395 (11), 291 (5),
acid (0.2 mL) were added. After heating for 15 min, the
3
1
06 (100), 105 (15), 82 (2), 77 (53). Anal. Calcd for
product filtered off and washed with boiling ethanol to give
23a. Yield 65%, (white powder), mp > 300°C; IR (KBr):
C H N O (658.85): Calcd C 80.21, H 6.43, N 8.50.
4
4 42 4 2
Found C 80.19, H 6.40, N 8.47.
ν = 3400 (NH), 2950, 2850, 1619 (C═C), 1523, 1463,
ꢀ
1
1,4-Phenylenebis((1,3-di(pyridin-2-yl)-1,2,3,4-tetrahydropyrimidin-
1345, 1195, 1089 cm ; MS (EI, 70 eV): m/z (%) = 263
+
+
+
5-yl)methane-one) (20b).
Yield 55%, (yellow powder), mp
(6) [M] , 262 (4) [M ꢀ 1] , 261 (16) [M ꢀ 2] , 185 (3)
+ +
2
85–286°C; IR (KBr): ν = 1669 (C═O), 1581, 1473, 1439,
[M-Ph] , 91 (31) [p-tolyl ion] , 77 (100). Anal. Calcd for
ꢀ
1
1239, 1151 cm ; MS (EI, 70 eV): m/z (%) = 608 (4)
C H N (263.34): Calcd C 77.54, H 6.51, N 5.96; Found
17 17 3
+
+
+
+
[
6
M + 2] , 607 (6) [M + 1] , 606 (8) [M] , 605 (1) [M ꢀ 1] ,
C 77.51, H 6.48, N 5.88.
7-Phenyl-4-(pyridin-2-yl)-3,4-dihydro-2H-1,2,4-triazepine
(23b). This compound was obtained from 2e as described
+
04 (6) [M ꢀ 2] , 528 (8), 450 (8), 369 (100), 266 (10), 81
(48), 77 (20). Anal. Calcd for C H N O (606.69): Calcd C
36 30 8 2
earlier for 23a. The crystalline solid that separated during
the reaction period was filtered off, dried, and washed
with boiling ethanol to give 23b. Yield 60%, (white
7
1.27, H 4.98, N 18.47. Found C 71.20, H 4.91, N 18.40.
These
compounds were obtained from 19a (0.39 g, 1 mmol) or
Synthesis of bis(tetrahydropyrimidines) 21a,b.
ꢀ
1
powder), mp > 300°C; IR (KBr): ν (cm) = 3411 (NH),
19b (0.37 g, 1 mmol), ammonium acetate (0.20 g,
1
7
601 (C═C), 1527, 1454, 1345, 1228, 1090; MS (EI,
0 eV): m/z (%) = 251 (2) [M + 1] , 250 (3) [M] , 118
2.5 mmol) and formalin 37% (0.2 mL, 2.5 mmol),
+
+
following the same procedure as described earlier for
compounds 20a–b. A crystalline solid separated during
the reaction period, and it was filtered off, dried, and
washed with boiling ethanol to give compounds 21a and
(
4), 78 (17), 77 (98), 43 (68). Anal. Calcd for C H N4
15 14
(250.31): Calcd C 71.98, H 5.64, N 22.38; Found: C
7
1.90, H 5.59, N 22.30.
1
,3-Bis(4-(4-methoxyphenyl)-2,7-diphenyl-3,4-dihydro-2H-
,2,4-triazepin-3-yl)propane (24). A solution of 2c (0.50 g,
mmol) and phenyl hydrazine (0.2 mL, 2 mmol) in
2
1b, respectively.
1
1
,4-Phenylenebis((1-(p-tolyl)-1,2,3,4-tetrahydropyrimidin-5-
2
yl)methanone) (21a).
Yield 65%, (yellow powder), mp
ethanol (20 mL) was heated on steam bath for 15 mins,
left at room temperature for 20 min, then glutaric
dialdehyde (50%, 0.2 mL, 1 mmol) and acetic acid
0.2 mL were added. The reaction mixture heated on
steam bath for 15 min. The solid that obtained on heating
filtered off, dried, and washed with boiling ethanol to
furnish 24. Yield 60%, (brown powder), mp 289–290°C;
IR (KBr): ν = 2930, 1625 (C═C), 1590, 1509,
2
90–291°C; IR (KBr): ν = 3434 (NH), 3038, 2923, 1668
ꢀ
1
(
(
C═O), 1622 (C═C), 1595, 1511, 1398, 1237 cm ; MS
EI, 70 eV): m/z (%) = 479 (4) [M + 1] , 478 (5) [M] ,
+
+
+
4
8
77 (12) [M ꢀ 1] , 394 (11), 296 (17), 105 (2), 91 (22),
1 (100), 76 (11), 42 (29). Anal. Calcd for C H N O
0 30 4 2
3
(478.60): Calcd C 75.29, H 6.32, N 11.71. Found C
7
5.22, H 6.28, N 11.68.
1,4-Phenylenebis((1-(pyridin-2-yl)-1,2,3,4-tetrahydropyrimidin-
ꢀ
1
5-yl)methanone) (21b).
Yield 50%, (yellow powder), mp
1460 cm ; MS (EI,70 eV): m/z (%) = 752 (46)
+
+
+
2
1
45–246°C; IR (KBr): ν = 3419 (NH), 1666 (C═O), 1570,
474, 1440, 1239 cm ; MS (EI, 70 eV): m/z (%) = 454
[M + 2] , 751 (53) [M + 1] , 750 (57) [M] , 688 (14)
ꢀ
1
+
+
[M–2 (OCH )] , 536 (4) [M–2 × (p-anisyl ions)] , 442
3
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

E. M. Afsah, E.-S. I. El-Desoky, H. A. Etman, I. Youssef, and A. M. Soliman
Vol 000
+
(
11), 107 (14) [p-anisyl ion] , 93 (5). Anal. Calcd for
[23] Almazroa, S.; Elnagdi, M. H.; Salah El-Din, A. M. J Heterocy-
clic Chem 2004, 41, 267.
C H N O (750.95): Calcd C 78.37, H 6.17, N 11.19.
4
9 46 6 2
[24] Al-Saleh, B.; Abdelkhalik, M. M.; Eltoukhy, A. M.; Elnagdi,
Found C 78.32, H 6.10, N 11.13.
M. H. J Heterocyclic Chem 2002, 39, 1035.
[25] Al-Shiekh, M. A.; Salah El-Din, A. M.; Hafez, E. H.; Elnagdi,
M. H. J Heterocyclic Chem 2004, 41, 647.
1
,2-Bis(7-phenyl-2,3-dihydro-4H-1,2,4-triazepin-4-yl)ethane
(25).
A solution of 15 (0.32 g, 1 mmol), hydrazine
[
26] Al-Mousawi, S.; Abdel-Khalik, M. M.; El-Sherbiny, S.; John,
E.; Elnagdi, M. H. J Heterocyclic Chem 2001, 38, 949.
27] Al-Awadi, N. A.; Elnagdi, M. H.; Ibrahim, Y. A.; Kaul, K.;
Kumar, A. Tetrahedron 2001, 57, 1609.
28] Riyadh, S. M.; Farghaly, T. A.; Gomha, S. M. Arch Pharm Res
010, 33, 1721.
hydrate (0.10 g, 2 mmol), and few drops of acetic acid in
ethanol (20 mL) was heated on steam bath for 30 min,
left at room temperature for 20 min, then formalin 37%
[
[
(
0.2 mL, 2.5 mmol) and acetic acid (0.2 mL) were added.
2
The reaction mixture heated for 15 min, the product that
obtained on heating filtered, dried, and washed with
boiling ethanol to give 25. Yield 60%, (white powder),
mp > 300°C; IR (KBr): ν = 3410 (NH), 1662 (C═C),
[
[
29] Riyadh, S. M. Molecules 2011, 16, 1834.
30] Wan, J.-P.; Gao, Y. Chem Rec 2016, 16, 1164.
[31] Chanda, K.; Dutta, M. C.; Karim, E.; Vishwakarma, J. N. J
Heterocyclic Chem 2004, 41, 627.
[32] Dutta, M. C.; Chanda, K.; Vishwakarma, J. N. J Heterocyclic
Chem 2005, 42, 121.
ꢀ
1
1
(
[
346, 1195, 1090 cm ; MS (EI, 70 eV): m/z (%) = 372
+
+
+
12) [M] , 370 (5) [M ꢀ 2] , 295 (8) [M-Ph] , 218 (8)
[33] Hammouda, M.; Hamama, W. S.; Afsah, E. M. Z Naturforsch
+
1
1
1
1
987, 42b, 94.
M-2 (Ph)] , 199 (14), 185 (7), 171 (4), 97 (63), 53 (18).
[34] Hamama, W. S.; Hammouda, M.; Afsah, E. M. Z Naturforsch
Anal. Calcd for C H N (372.48): Calcd C 70.94, H
.49, N 22.56. Found C 70.89, H 6.44, N 22.50.
2
2 24 6
988, 43b, 483.
6
[35] Miyano, S.; Abe, N. Chem Pharm Bull (Japan) 1972, 20,
588.
[36] Rashed, N.; Sayed, M.; El-Ashry, E. S. H. J Chin Chem Soc
993, 40, 189.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet