Synthesis of 2-aryl-1H-benzimidazoles and 2-aryl-1H-perimidines using arylidene Meldrum’s acid as a source of the aryl group and oxidant

Article abstract of DOI:10.3184/174751918X15199196317528

Arylidene Meldrum’s acid is employed as a source of the aryl group and oxidant for the synthesis of 2-aryl-1H–benzimidazoles by a condensation reaction with 1,2-phenylenediamine in refluxing ethanol with good to high yields. Arylidene Meldrum’s acids were

Full text of DOI:10.3184/174751918X15199196317528

JOURNAL OF CHEMICAL RESEARCH 2018
VOL. 42 MARCH, 125–128
RESEARCH PAPER 125
Synthesis of 2-aryl-1H-benzimidazoles and 2-aryl-1H-perimidines using
arylidene Meldrum’s acid as a source of the aryl group and oxidant
Hossein Mehrabi*, Faezeh Najafian-Ashrafi, Zeinab Esfandiarpour and Reza Ranjbar-Karimi
Department of Chemistry, Vali-e-Asr University of Rafsanjan, Rafsanjan 77176, Iran
Arylidene Meldrum’s acid is employed as a source of the aryl group and oxidant for the synthesis of 2-aryl-1H–benzimidazoles by a
condensation reaction with 1,2-phenylenediamine in refluxing ethanol with good to high yields. Arylidene Meldrum’s acids were also used
as a source of the aryl group and oxidant for the synthesis of 2-aryl-1H-perimidines by a condensation reaction with 1,8-diaminonaphthalene
in refluxing ethanol with high yields.
Keywords: arylidene Meldrum’s acid, 2-aryl-1H-benzimidazoles, 2-aryl-1H-perimidines
Multinuclear N-heterocyclic compounds such as perimidines
and benzimidazoles are of wide interest because they exhibit
a diverse range of biological activities.1,2 Differently substituted
benzimidazoles have been associated with an extensive
range of biological activities, including antiviral, antifungal,
antimicrobial, antiprotozoal, anti-inflammatory, anticancer,
antioxidant, anticoagulant, antidiabetic and antihypertensive
activities.3–7
out under the same reaction conditions through the reaction
of 1,2-phenylenediamine 1 and a wide variety of arylidene
Meldrum’s acids 3a–k with high yields (Table 1). In addition,
under the optimised reaction conditions, a series of 2-substituted
perimidines 5a–i were synthesised. To explore the scope of this
novel transformation, various arylidene Meldrum’s acids 3a–i
with 1,8-diaminonaphthalene 2 were utilised under the same
reaction conditions (Table 2).
In view of the biological importance of benzimidazoles
and perimidines there has been growing interest in the
development of synthetic methods for the preparation of these
heterocycles. For the synthesis of 2-substituted benzimidazoles
the condensation of 1,2-phenylenediamine and aldehydes with
subsequent oxidation has been studied using various oxidative
reagents such as nitrobenzene (high-boiling point oxidant/
solvent),8–10 I2,11 Fe(III)/Fe(II),12 In(OTf)3,13 PhI(OAc)2,14
Sc(OTf)3,15,16 Yb(OTf)3,17 heteropoly acids,18 thionyl chloride
treatment,19 MnO2,20 Pb(OAc)4,21 oxone,22 NaHSO3,23 H2O2/
HCl,24 Na2S2O5,25 potassium persulfate–CuSO4,26 potassium
ferricyanide,27 H2O2/CAN,28 H2O2/Fe(NO3)3,29 cobalt(III)–
salen complex supported on activated carbon30 and Cu(II)
complex.31 The most commonly used method for the preparation
of 2-substituted perimidines is the condensation reaction of
1,8-diaminonaphthalene with a carbonyl group, which requires
a special reagent or forced reaction conditions.32–38 Although
all of these methods are widely employed they all suffer
from one or other disadvantage, such as the formation of by-
products, tedious work-up procedures or the use of expensive,
toxic and air-sensitive oxidative reagents. In addition, in most
synthetic routes, the first step is the preparation of 2,3-dihydro-
perimidine or 2,3-dihydro- benzimidazole using acid catalysis,
and in a subsequent step dehydrogenation is effected using an
oxidant reagent. Thus, there is still a need to search for better
oxidants and a procedure with operational simplicity.
Table 1 Synthesis of 2-aryl-1H-benzimidazoles
O
H
NH2
NH2
O
O
N
EtOH
+
R
N
Reflux
O
R
4a-k
3a-k
1
Product
4a
4b
4c
4d
4e
4f
4g
4h
R
H
3-Cl
4-Cl
4-F
4-Br
4-CH3
4-CF3
4-N(CH3)2
2-CH3
2-NO2
2-Cl
Time (h)
Yield (%)a M.p. (oC)
4
3
4
2
4
5
2
5
5
4
3
90
78
90
92
80
75
85
70
72
85
83
292–294 (289–291)14
230–232 (235–237)39
295–296 (292–294)14
252–254 (249–251)40
292–294 (298)41
272–274 (277)11
264–266
210–212 (215)42
4i
4j
4k
211–214
269–271 (263–265)39
228–230 (233–234)39
aYields are given for the isolated products
Table 2 Synthesis of 2-aryl-1H-perimidines
O
O
NH
NH2
EtOH
+
O
Reflux
R
N
NH2
O
Given these considerations, here we report a simple
and efficient method for the synthesis of 2-aryl-1H-
benzimidazoles and 2-aryl-1H-perimidines through reaction
of 1,2-phenylenediamine or 1,8-diaminonaphthalene with two
equivalents of arylidene Meldrum’s acid, not only as the aryl
group donor, but also as the organic oxidant.
R
5a-i
3a-i
2
Product
5a
5b
5c
5d
5e
5f
5g
5h
R
4-Cl
Time (h)
4.5
5.5
6.5
4.0
4.0
5.5
7.0
4.5
Yield (%)a M.p. (oC)
92
80
77
87
88
78
80
84
86
176–178 (179–181)43
159–161 (160–162)44
139–141
4-CH3
2,3-(OCH3)2
4-NO2
3-NO2
4-OCH3
2,4-(OCH3)2
2-Cl
177–179
Results and discussion
161–163 (162–164)43
122–125 (120–122)44
151–150
The optimised conditions for the condensation of
1,2-phenylenediamine 1 and benzylidene Meldrum’s acid
3a are 1,2-phenylenediamine (1.0 mmol) and benzylidene
Meldrum’s acid (2.0 mmol) in ethanol (10.0 mL) under reflux
conditions. To explore the scope and generality of this method
the synthesis of 2-substituted benzimidazoles 4a–k was carried
149–150
163–161
5i
4-F
4.0
aYields are given for the isolated products
* Correspondent. E-mail: mehraby_h@yahoo.com

126 JOURNAL OF CHEMICAL RESEARCH 2018
R
O
NH2
O
NH2
NH2
O
O
O
N
H
O
O
NH2
N
+
O
O
Michael-Addition
O
R
O
7
6
3
1
O
R
O
O
O
O
H
H
H
N
O
O
H
N
N
8
O
+
N
R
3
R
R
O
H
R
H
Reduction-Oxidation
4
9
5
or when 1,8-diaminonaphthalene used
Scheme 1 Proposed mechanism for the synthesis of 2-aryl-1H-benzimidazoles 4 and 2-aryl-1H-perimidines 5.
As can be seen from Tables 1 and 2, electronic effects and the
nature of substituents on the aromatic ring resulted in products
with different reaction times and yields. When aromatic
aldehydes containing electron-donating groups (such as methyl,
methoxy or dimethylamino) were employed, a longer reaction
time and lower yield was required than for those of electron-
withdrawing groups (such as trifluoromethyl, nitro or halides)
on the aromatic rings.
1H–benzimidazoles and 2-aryl-1H-perimidines using arylidene
Meldrum’s acid. This method offers several advantages,
compared with those reported in the literature: (1) it uses a new,
readily available and inexpensive reagent, (2) it uses the reagent
not only as the source of the aryl group but also as the oxidant,
(3) it has short reaction times, and (4) the product is easily
isolated and purified, making it a useful and attractive strategy
for the synthesis of these products.
The known compounds were identified by comparison of
their melting points with those reported in the literature (see
references in Tables 1 and 2). In addition a number of these
Experimental
All chemicals were of high-grade quality and were purchased from
either Aldrich or Merck and used without further purification. All
melting points were obtained on a Bamslead Electrothermal 9200
apparatus and are uncorrected. The reactions were monitored by thin-
layer chromatography (TLC) and all yields refer to isolated products.
1H and 13C NMR spectra were recorded in DMSO on a Bruker 300 and
400 MHz spectrometer. Infrared spectra were recorded on a Bruker
FT-IR Equinax-55 spectrophotometer in KBr with absorption maxima
quoted in cm−1. Elemental analyses were performed using a Carlo Erba
EA 1108 instrument.
1
compounds were characterised by H and 13C NMR, IR and
CHN analysis.
A possible mechanism for the synthesis of 2-substituted
benzimidazoles 4 and 2-substituted perimidines 5 is illustrated
in Scheme 1. This conversion involves the initial reaction of the
1,2-phenylenediamine 1 with arylidene Meldrum’s acid 3 to
form the intermediate 6 via a Michael addition reaction. This
intermediate is then converted to Schiff base 7 by eliminating
Meldrum’s acid as a good leaving group. Continuing, the amine
group in Schiff base 7 undergoes an intramolecular nucleophilic
addition to the imine group, generating dihydro-benzimidazole
8. Finally, the benzimidazole 4 is formed through a simple and
efficient intermolecular hydrogen transfer between intermediate
8 as a reductant and arylidene Meldrum’s acid 3 as an oxidant.
Aryldihydro Meldrum’s acid 9 was isolated and characterised by
Representative experimental procedure
To
a magnetically stirred solution of 1,2-phenylenediamine 1
(1.0 mmol) or 1,8-diaminonaphthalene 2 (1.0 mmol) in ethanol (5 mL)
was added dropwise arylidene Meldrum’s acid 3 (2.0 mmol) in ethanol
(5 mL) at room temperature over 5 min. The reaction mixture was then
stirred at reflux conditions for an appropriate time. After completion
of the reaction, determined by TLC, the solvent was removed under
reduced pressure and the resulting crude product was recrystallised
from water to give the pure compounds 4a–k and 5a–i. For the
preparation of 4e and 5a, after removal of the solvent, the mixture of
products was separated by chromatography on silica gel plates using
hexane/ethyl acetate (2:1) to give 9a and 9b as well as 4e and 5a.
1
spectroscopic techniques. For example, the H NMR spectrum
of compound 9a consisted of a singlet at δ 0.54 ppm for the two
methyl protons. Two doublets occurred at δ 3.32 and 3.45 ppm
with coupling constants of 4.5 and 14.1 Hz, respectively, for
the methylene protons. In addition, a doublet and a doublet at
δ 4.01 ppm that integrated for one hydrogen, with coupling
constants of 14.1 and 4.5 Hz, respectively, for the methine
proton were also observed. A multiplet at δ 6.92–7.27 ppm for
the aromatic protons of the phenyl ring was also observed. The
1H-decoupled 13C NMR spectrum of compound 9a showed
11 distinct signals, in agreement with the proposed structure.
Partial assignments of these resonances and those of compound
9b are given in the experimental section.
Physical and spectroscopic data for compounds 4a–k and 5a–i
2-Phenyl-1H-benzimidazole (4a): IR (KBr) (νmax/cm−1): 3447, 3048,
1
2966, 2853, 1621, 1494, 1384, 1180, 1028, 970; H NMR (300 MHz,
DMSO-d6): δ (ppm) 7.20 (d, 2H, J = 4.8 Hz, ArH), 7.44–7.56 (m, 4H,
ArH), 7.67 (br s, 1H, ArH), 8.20 (d, 2H, J = 7.2 Hz, ArH), 12.94 (s, 1H,
NH).
2-(3-Chlorophenyl)-1H-benzimidazole (4b): IR (KBr) (νmax/cm−1):
3442, 3047, 2965, 1602, 1442, 1384, 1362, 1285, 1124, 1080, 977;
1H NMR (300 MHz, DMSO-d6): δ (ppm) 7.17–7.26 (m, 2H, ArH),
7.52–7.60 (m, 3H, ArH), 7.67 (d, 1H, J = 7.5 Hz, ArH), 8.13 (d, 1H,
J = 6.9 Hz, ArH), 8.21 (s, 1H, ArH), 13.02 (s, 1H, NH).
Conclusions
In summary, we have developed an efficient synthesis that is
high-yielding under mild conditions for the synthesis of 2-aryl-

JOURNAL OF CHEMICAL RESEARCH 2018 127
2-(4-Chlorophenyl)-1H-benzimidazole (4c): IR (KBr) (νmax/cm−1):
3442, 3052, 2995, 2955, 1881, 1622, 1471, 1448, 1384, 1320, 1225, 1119,
963. 1H-NMR (300 MHz, DMSO-d6): δ (ppm) 7.17–7.35 (m, 2H, ArH),
7.60 (d, 4H, J = 8.4 Hz, ArH), 8.20 (d, 2H, J = 8.4 Hz, ArH), 12.92 (br
s, 1H, NH).
2-(4-Fluorophenyl)-1H-benzimidazole (4d): IR (KBr) (νmax/cm−1):
3447, 3053, 2964, 1623, 1498, 1452, 1397, 1228, 1156, 1110, 968;
1H NMR (300 MHz, DMSO-d6): δ (ppm) 7.16–7.22 (m, 2H, ArH),
7.39 (t, 2H, J = 8.7 Hz, ArH), 7.58 (br s, 2H, ArH), 8.18–8.23 (dd, 2H,
J = 8.4 and 5.4 Hz, ArH), 12.91 (br s, 1H, NH).
2-(2,3-Dimethoxyphenyl)-1H-perimidine (5c): IR (KBr) (νmax/
cm−1): 3343, 2990, 2857, 1611, 1594, 1447, 1422, 1411, 1594; 1H NMR
(400 MHz, DMSO-d6): δ (ppm) 3.85 (s, 3H, OCH3), 3.90 (s, 3H,
OCH3), 6.49–7.23 (m, 10H, ArH and NH); 13C NMR (100 MHz,
DMSO-d6): δ (ppm) 56.0, 56.4, 98.9, 105.3, 105.9, 112.6, 114.8, 118.5,
121.9, 127.1, 128.9, 131.6, 135.6, 153.0, 158.9, 162.8; Anal. calcd for
C19H16N2O2 (304.35): C, 74.98; H, 5.30; N, 9.20; found: C, 75.09; H,
5.33; N, 9.14%.
2-(4-Nitrophenyl)-1H-perimidine (5d): IR (KBr) (νmax/cm−1):
1
3364, 2983, 1601, 1513, 1420, 1350; H NMR (400 MHz, DMSO-d6):
2-(4-Bromophenyl)-1H-benzimidazole (4e): IR (KBr) (νmax/cm−1):
3447, 3051, 2950, 1622, 1470, 1428, 1320, 1274, 1113, 1070, 963;
1H NMR (300 MHz, DMSO-d6): δ (ppm)7.16–7.25 (m, 2H, ArH), 7.52
(d, 1H, J = 7.2 Hz, ArH), 7.65 (d, 1H, J = 7.2 Hz, ArH), 7.75 (d, 2H,
J = 8.4 Hz, ArH), 8.11 (d, 2H, J = 8.4 Hz, ArH), 12.98 (s, 1H, NH).
2-(4-Methylphenyl)-1H-benzimidazole (4f): IR (KBr) (νmax/cm−1):
3447, 3053, 3026, 2965, 2917, 1621, 1588, 1447, 1398, 1274, 1154,
1041, 964; 1H NMR (300 MHz, DMSO-d6): δ (ppm) 2.36 (s, 3H, CH3),
7.17–7.18 (m, 2H, ArH), 7.34 (d, 2H, J = 8.1 Hz, ArH), 7.51–7.62 (m,
2H, ArH), 8.07 (d, 2H, J = 8.1 Hz, ArH), 12.82 (s, 1H, NH).
2-(4-Trifluoromethylphenyl)-1H-benzimidazole (4g): IR (KBr)
(νmax/cm−1): 3447, 3053, 2964, 1623, 1498, 1452, 1397, 1228, 1156,
1110, 968; 1H NMR (300 MHz, DMSO-d6): δ (ppm) 7.19–7.28 (m, 2H,
ArH), 7.56 (d, 1H, J = 7.8 Hz, ArH), 7.70 (d, 1H, J = 7.8 Hz, ArH), 7.92
(d, 2H, J = 8.1 Hz, ArH), 8.38 (d, 2H, J = 8.1 Hz, ArH), 13.16 (s, 1H,
NH); 13C NMR (75 MHz, DMSO-d6): δ (ppm) 122.32, 123.17, 128.15,
129.06, 134.52, 150.19; Anal. calcd for C14H9F3N2 (262.24): C, 64.12;
H, 3.46; N, 10.68; found: C, 64.19; H, 3.48; N, 10.65%.
δ (ppm) 5.54 (s, 1H, NH), 6.52 (d, 2H, J = 7.2 Hz, ArH), 7.00 (m, 2H,
J = 8.8 Hz, ArH), 7.18 (m, 2H, J = 7.2 Hz, ArH), 7.84 (d, 2H, J = 8.8 Hz,
ArH), 8.30 (m, 2H, ArH); 13C NMR (100 MHz, DMSO-d6): δ (ppm)
65.3, 105.0, 107.9, 112.8, 116.0, 119.9, 123.8, 127.4, 128.7, 129.5, 134.7,
142.5, 144.6, 147.8, 150.3; Anal. calcd for C17H11N3O2 (289.29): C,
70.58; H, 3.83; N, 14.53; found: C, 70.52; H, 3.79; N, 14.48%.
2-(3-Nitrophenyl)-1H-perimidine (5e): IR (KBr) (νmax/cm−1): 3345,
3038, 1602, 1528, 1416, 1351; 1H NMR (400 MHz, DMSO-d6): δ (ppm)
5.50 (s, 1H, NH), 6.52 (d, 1H, J = 6.8 Hz, ArH), 7.01 (m, 3H, J = 7.6 Hz,
ArH), 7.18 (m, 2H, J = 8.0 Hz, ArH), 7.73 (m, 1H, J = 8.0 Hz, ArH),
8.0 (m, 1H, J = 7.6 Hz, ArH), 8.28 (m, 1H, J = 6.8 Hz, ArH), 8.46 (m,
1H, ArH); 13C NMR (100 MHz, DMSO-d6): δ (ppm) 65.2, 105.0, 116.1,
122.0, 122.3, 123.0, 123.7, 127.4, 129.0, 130.3, 130.7, 133.8, 135.0,
135.4, 142.6, 145.0, 148.3.
2-(4-Methoxyphenyl)-1H-perimidine (5f): IR (KBr) (νmax/cm−1):
3446, 3037, 2924, 2838, 1611, 1598, 1512, 1465, 1437; 1H NMR
(400 MHz, DMSO-d6): δ (ppm) 3.86 (s, 3H, OCH3), 6.62 (s, 1H, NH),
6.62–8.03 (m, 10H, ArH); 13C NMR (100 MHz, DMSO-d6): δ (ppm)
55.9, 114.1, 117.3, 118.7, 121.8, 125.9, 127.3, 128.9, 131.0, 135.5, 137.5,
140.0, 141.9, 152.6, 154.4, 162.0.
2-(4-Dimethylaminophenyl)-1H-benzimidazole (4h): IR (KBr) (νmax
/
cm−1): 3447, 3061, 2965, 2906, 1606, 1549, 1528, 1491, 1367, 1165;
1H NMR (300 MHz, DMSO-d6): δ (ppm) 3.0 (s, 6H, NMe2), 6.84 (d,
2H, J = 9.0 Hz, ArH), 7.13–7.16 (m, 2H, ArH), 7.49–7.52 (m, 2H, ArH),
7.98 (d, 2H, J = 9.0 Hz, ArH), 12.89 (s, 1H, NH).
2-(2,4-Dimethoxyphenyl)-1H-perimidine (5g): IR (KBr) (νmax
/
cm−1): 3348, 3044, 2998, 1600, 1517, 1485, 1414; 1H NMR (400 MHz,
DMSO-d6): δ (ppm) 3.78 (s, 3H, CH3), 3.79 (s, 3H, CH3), 5.35 (s, 1H,
NH), 6.49 (m, 2H, ArH), 6.69 (m, 2H, ArH), 6.99 (m, 2H, J = 7.6 Hz,
ArH), 7.14 (m, 2H, J = 7.6 Hz, ArH), 7.23 (m, 2H, ArH); 13C NMR
(100 MHz, DMSO-d6): δ (ppm) 56.1, 56.2, 104.7, 111.6, 111.8, 115.6,
119.3, 120.6, 120.8, 127.3, 128.9, 134.5, 134.8, 135.3, 143.7, 148.9, 149.1,
149.5; Anal. calcd for C19H16N2O2 (304.35): C, 74.98; H, 5.30; N, 9.20;
found: C, 74.88; H, 5.29; N, 9.16%.
2-(2-Methylphenyl)-1H-benzimidazole (4i): IR (KBr) (νmax/cm−1):
3447, 3061, 2967, 2920, 2877, 2789, 2673, 1589, 1490, 1403, 1384,
1
1277, 1207, 1011, 975; H NMR (300 MHz, DMSO-d6): δ (ppm) 2.40
(s, 3H, CH3), 7.14–7.22 (m, 2H, ArH), 7.29 (d, 1H, J = 7.5 Hz, ArH),
7.42 (t, 1H, J = 7.8 Hz, ArH), 7.51 (d, 1H, J = 7.5 Hz, ArH), 7.64 (d,
1H, J = 7.2 Hz, ArH), 7.95 (d, 1H, J = 7.8 Hz, ArH), 8.01 (s, 1H, ArH),
12.86 (s, 1H, NH); 13C NMR (75 MHz, DMSO-d6): δ (ppm) 24.52,
122.21, 127.39, 129.98, 130.32, 131.15, 131.64, 132.07, 149.10; Anal.
calcd for C14H12N2 (208.26): C, 80.74; H, 5.81; N, 13.45; found: C,
80.69; H, 5.78; N, 13.40%.
2-(2-Nitrophenyl)-1H-benzimidazole (4j): IR (KBr) (νmax/cm−1):
3447, 3064, 2864, 2655, 1611, 1574, 1446, 1379, 1348, 1278, 1140,
1078; 1H NMR (300 MHz, DMSO-d6): δ (ppm) 7.25 (br s, 2H,
ArH), 7.69 (br s, 2H, ArH), 7.73 (t, 1H, J = 7.8 Hz, ArH), 7.84 (t, 1H,
J = 7.5 Hz, ArH), 7.98 (d, 1H, J = 7.8 Hz, ArH), 8.02 (d, 1H, J = 7.8 Hz,
ArH), 13.08 (s, 1H, NH).
2-(2-Chlorophenyl)-1H-perimidine (5h): IR (KBr) (νmax/cm−1):
1
3386, 3048, 2924, 2853, 1635, 1596, 1477, 1371; H NMR (400 MHz,
DMSO-d6): δ (ppm) 7.08–7.64 (m, 10H, ArH), 10.90 (s, 1H, NH);
13C NMR (100 MHz, DMSO-d6): δ (ppm) 119.2, 122.1, 123.9, 126.8,
127.1, 127.9, 128.9, 130.1, 130.8, 131.6, 131.8, 134.9, 135.6, 142.3, 153.4;
Anal. calcd for C17H11ClN2 (278.74): C, 73.25; H, 3.98; N, 10.05; found:
C, 73.17; H, 3.96; N, 10.01%.
2-(4-Fluorophenyl)-1H-perimidine (5i): IR (KBr) (νmax/cm−1): 3313,
1
2987, 2853, 1636, 1595, 1442, 1425; H NMR (400 MHz, DMSO-d6):
δ (ppm) 6.63 (m, 2H, ArH), 7.05 (d, 2H, J = 8.0 Hz, ArH), 7.17 (d, 2H,
J = 8.0 Hz, ArH), 7.39 (d, 2H, J = 8.8 Hz, ArH), 8.10 (d, 2H, J = 8.8 Hz,
ArH), 10.70 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6): δ (ppm)
114.4, 115.7, 115.9, 119.0, 121.9, 128.9, 129.8, 129.8, 130.3, 130.3, 131.9,
132.0, 135.5, 152.2, 165.4; Anal. calcd for C17H11FN2 (262.29): C,
77.85; H, 4.23; N, 10.68; found: C, 77.83; H, 4.19; N, 10.64%.
2-(2-Chlorophenyl)-1H-benzimidazole (4k): IR (KBr) (νmax/cm−1):
3447, 3048, 1936, 1622, 1590, 1443, 1404, 1231, 1110, 1026; 1H NMR
(300 MHz, DMSO-d6): δ (ppm) 7.20–7.26 (m, 2H, ArH), 7.47–7.55 (m,
2H, ArH), 7.62–7.65 (m, 3H, ArH), 7.89–7.92 (m, 1H, ArH), 12.74 (s,
1H, NH).
2-(4-Chlorophenyl)-1H-perimidine (5a): IR (KBr) (νmax/cm−1):
5-(4-Bromobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione
(9a):
1
3298, 2995, 2850, 1635, 1598, 1447, 1426, 1414; H NMR (400 MHz,
M.p. 127–129 °C; Yield 83%; IR (KBr) (νmax/cm−1): 1758, 1731,
1605, 1587, 1491, 1391, 1377, 1303, 1285, 1114; 1H NMR (300 MHz,
CDCl3): δ (ppm) 0.54 (s, 6H, 2CH3), 3.32 (d, J = 4.5 Hz, 1H, CH2),
3.45 (d, J = 14.1 Hz, 1H, CH2), 4.01 (dd, J = 14.1 and 4.5 Hz, 1H, CH),
6.92–7.27 (m, 4H, ArH); 13C NMR (75 MHz, CDCl3): δ (ppm) 20.95,
42.32, 48.73, 105.90, 128.73, 129.00, 137.36, 138.21, 167.51; Anal. calcd
for C13H13BrO4 (313.15): C, 49.86; H, 4.18; found: C, 49.97; H, 4.21%.
DMSO-d6): δ (ppm) 6.54 (d, 2H, J = 7.2 Hz, ArH), 6.96 (d, 2H,
J = 7.2 Hz, ArH), 7.99 (m, 4H, ArH), 7.62 (d, 2H, J = 8. Hz, ArH), 8.04
(d, 2H, J = 8.8 Hz, 2H, ArH), 10.71(s, 1H, NH); 13C NMR (100 MHz,
DMSO-d6): δ (ppm) 107.8, 122.0, 124.2, 125.2, 128.7, 128.9, 129.0,
129.1, 132.5, 135.5, 136.2, 141.3, 143.7, 152.1.
2-(4-Methylphenyl)-1H-perimidine (5b): IR (KBr) (νmax/cm−1):
1
3287, 3048, 2920, 1635, 1601, 1509, 1444, 1372; H NMR (400 MHz,
5-(4-Chlorobenzyl)-2,2-dimethyl-1,3-dioxane-4,6-dione
(9b):
DMSO-d6): δ (ppm) 2.31 (s, 3H, CH3), 6.62 (m, 2H, J = 8.4 Hz, ArH),
7.03 (d, 2H, J = 8.4 Hz, ArH), 7.14 (m, 2H, J = 8.4 Hz, ArH), 7.34 (d,
2H, J = 8.4 Hz, ArH), 7.93 (d, 2H, J = 8.4 Hz, ArH), 10.61 (s, 1H, NH);
13C NMR (100 MHz, DMSO-d6): δ (ppm) 21.48, 109.0, 118.9, 119.0,
120.4, 121.9, 127.2, 128.8, 128.9, 131.0, 135.5, 139.6, 141.4, 152.9.
M.p. 147–149 °C; Yield 80%; IR (KBr) (νmax/cm−1): 1754, 1725, 1514,
1394, 1382, 1362, 1287, 1194; 1H NMR (300 MHz, CDCl3): δ (ppm)
0.53 (s, 6H, 2CH3), 3.33 (d, J = 4.3 Hz, 1H, CH2), 3.46 (d, J = 14.1 Hz,
1H, CH2), 4.00 (dd, J = 14.1 and 4.3 Hz, 1H, CH), 7.02 (d, J = 7.8 Hz,
2H, ArH), 7.16 (d, J = 7.8 Hz, 2H, ArH); 13C NMR (75 MHz, CDCl3):

128 JOURNAL OF CHEMICAL RESEARCH 2018
19 A.B. Alloum, K. Bougrin and M. Soufiaoui, Tetrahedron Lett., 2003, 44,
5935.
δ (ppm) 20.50, 42.36, 48.42, 105.85, 128.04, 129.42, 134.27, 137.81,
167.61; Anal. calcd for C13H13ClO4 (268.69): C, 58.11; H, 4.88; found:
C, 58.19; H, 4.91%.
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R. Villalobos-Molina, O. Munoz-Muniz and S. Estrada-Soto, Bioorg. Med.
Chem. Lett., 2006, 16, 4169.
Received 3 December 2017; accepted 23 February 2018
Paper 1705133
https://doi.org/10.3184/174751918X15199196317528
Published online: 14 March 2018
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