2-Aryl-6,8-dibromo-2,3-dihydroquinazolin-4(1h)-ones as substrates for the synthesis of 2,6,8-triarylquinazolin-4-ones

Article abstract of DOI:10.4314/bcse.v28i1.10

Direct bromination of 2-aminobenzamide was achieved using N-bromosuccinimide in chloroform-carbon tetrachloride mixture at room temperature for 3 h to afford 2-amino-3,5-dibromobenzamide in high yield and purity. 2-Amino-3,5-dibromobenzamide was, in turn,

Full text of DOI:10.4314/bcse.v28i1.10

Bull. Chem. Soc. Ethiop. 2014, 28(1), 81-90.
Printed in Ethiopia
ISSN 1011-3924
 2014 Chemical Society of Ethiopia
DOI: http://dx.doi.org/10.4314/bcse.v28i1.10
2-ARYL-6,8-DIBROMO-2,3-DIHYDROQUINAZOLIN-4(1H)-ONES AS SUBSTRATES
FOR THE SYNTHESIS OF 2,6,8-TRIARYLQUINAZOLIN-4-ONES
Malose J. Mphahlele*, Marole M. Maluleka and Tebogo A. Khoza
Department of Chemistry, College of Science, Engineering and Technology, University of
South Africa, P.O. Box 392, Pretoria 0003, South Africa
(Received June 14, 2013; revised November 13, 2013)
ABSTRACT. Direct bromination of 2-aminobenzamide was achieved using N-bromosuccinimide in
chloroform-carbon tetrachloride mixture at room temperature for 3 h to afford 2-amino-3,5-dibromobenzamide in
high yield and purity. 2-Amino-3,5-dibromobenzamide was, in turn, condensed with benzaldehyde derivatives in
the presence of boric acid to afford novel 2-aryl-6,8-dibromo-2,3-dihydroquinazolin-4(1H)-ones. Suzuki-Miyaura
cross-coupling of the latter with arylboronic acids yielded the corresponding 2,6,8-triaryl-2,3-dihydroquinazolin-
4(1H)-ones. These triarylquinazolin-4(1H)-ones were dehydrogenated using iodine (2 equiv.) in ethanol under
reflux to yield the potentially tautomeric 2,6,8-triarylquinazolin-4(3H)-ones.
KEY WORDS: 2-Amino-3,5-dibromobenzamide, 2-Aryl-6,8-dibromo-2,3-dihydroquinazolin-4(1H)-ones,
Suzuki-Miyaura cross-coupling, 2,6,8-Triaryl-2,3-dihydroquinazolin-4(1H)-ones, 2,6,8-Triarylquinazolin-4(3H)-
ones
INTRODUCTION
The 2,3-dihydroquinazolin-4(1H)-one–based compounds continue to attract considerable attention
in synthesis because of their rich biological activities and excellent pharmacological properties [1-
5]. These compounds are generally accessible via the condensation of isatoic anhydride or
anthranilamide derivatives with aldehydes or ketones using p-toluenesulfonic acid [5], HCl [6],
samarium iodide [7], TiCl4–Zn [8], NH4Cl [9], boric acid [10], cerium(IV) ammonium nitrate [11],
iodine [12], gallium(III) triflate [13] or β-cyclodextrin [14] as catalysts. Molecular iodine catalyzed
condensation of isatoic anhydride with benzaldehyde derivatives in the presence of NH4OAc in
ethanol under reflux, on the other hand, previously afforded the 2-arylquinazolin-4(3H)-ones
exclusively or along with the 2,3-dihydroquinazolin-4(1H)-ones depending on the ratio of iodine
used [15]. A thorough literature search revealed that the 2-substituted 2,3-dihydroquinazolin-
4(1H)-one derivatives bearing carbon-containing groups (aryl, alkenyl, alkynyl) on the fused benzo
ring remain surprisingly unexplored so far. In our view, such polysubstituted derivatives can be
readily accessible via transition metal catalyzed cross-coupling of the corresponding pre-
synthesized halogenated 2,3-dihydroquinazolin-4(1H)-ones. We envisioned that the 2-aryl-6,8-
dibromo-2,3-dihydroquinazolin-4(1H)-ones represent potential candidates for such transformation
to afford novel polysubstituted quinazolin-4(1H)-ones bearing carbon- or heteroatom-containing
substituents. We herein describe the synthesis of the 2-aryl-6,8-dibromo-2,3-dihydroquinazolin-
4(1H)-ones and sequential transformation via the Suzuki-Miyaura cross-coupling with arylboronic
acids followed by dehydrogenation to afford novel polysubstituted quinazolin-4(3H)-one
derivatives.
RESULTS AND DISCUSSION
The first task in this investigation was to synthesize the requisite 2-aryl-6,8-dibromo-2,3-
dihydroquinazolin-4(1H)-ones from 2-amino-3,5-dibromobenzamide and benzaldehyde
derivatives. 2-Amino-3,5-dibromobenzamide required as a precursor for this purpose was prepared
__________
*Corresponding author. E-mail: mphahmj@unisa.ac.za

82
Malose J. Mphahlele et al.
before in 85% yield by treatment of (2-amino-3,5-dibromophenyl)(benzotriazole-1-yl)methanone
with excess aqueous ammonium hydroxide in THF at °C [16]. The labeled 3,5-
0
dibromo[13C7]anthranilamide, on the other hand, has been prepared in 47% yield by acid
hydrolysis of 2-amino-3,5-dibromo-[13C7]-benzonitrile [17]. Although 2-aminobenzamide is
commercially available and has been used in several transformations before, to our knowledge,
direct bromination of this compound has not been explored so far. On the other hand, the
analogous 2'-aminoacetophenone has been found to undergo bromination with NaBr-oxone in
acetonitrile [18], Br2 in acetic acid [19], or N-bromosuccinimide (NBS) in CHCl3-CCl4 mixture
[20] to afford 2-amino-3,5-dibromoacetophenone in high yield. Based on these literature
precedents, we subjected anthranilamide 1 to NBS (2.5 equiv.) in chloroform-carbon tetrachloride
mixture (3/2, v/v) at room temperature. To our delight, we isolated directly after 3 h by filtration
and recrystallization, a product characterized using a combination of NMR and IR spectroscopic
techniques as well as mass spectrometry as the 3,5-dibromoanthranilamide 2 (Scheme 1). Whereas
benzamide was found to react with NaBr-oxone mixture to afford N-bromobenzamide [18] in our
case, no product resulting from possible N-bromination was detected or isolated from the reaction
mixture. Compound 2 was, in turn, condensed with benzaldehyde derivatives (1 equiv.) under
solvent-free conditions using boric acid as a catalyst following a literature method [10] to afford
the corresponding novel 2-aryl-6,8-dibromo-2,3-dihydroquinazolin-4(1H)-ones 3a-d (Scheme 1).
A series of the analogous 2,3-disubstituted 6,8-dibromoquinazolin-4(3H)-one derivatives has
nevertheless been synthesized before from the reaction of 6,8-dibromo-2-methyl-1-benzoxazin-
3(4H)-one with nitrogen nucleophiles such as hydrazine hydrate, sulpha drugs and 4'-
aminoacetophenone [21]. The 6-fluoro-8-(iodo/bromo)-2-methylquinazolin-4(3H)-ones, on the
other hand, have been prepared via the reaction of 6-fluoro-8-iodo/bromo-2-methyl-1-benzoxazin-
3(4H)-ones with aqueous ammonia under reflux [22].
O
O
O
H
Br
Br
N
NH2
NH2
NH2
NH2
(i)
(ii)
N
H
C6H4R
Br
Br
1
2 (83%)
3a-d
R
% Yield 3
3a
3b
3c
3d
4-H
4-F
4-Cl
4-OMe
87
82
90
86
Reagents and conditions: (i) NBS, CHCl3-CCl4 (3/2, v/v), rt, 3 h; (ii) ArCHO, boric acid (20 mol %), 120 °C,
5 min.
Scheme 1. Synthesis of the 2-aryl-6,8-dibromo-2,3-dihydroquinazolin-4(1H)-ones 3a-d.
The need to access a diverse range of the 2,3-dihydroquinazolin-4(1H)-ones bearing carbon-
containing substituents on the fused benzo ring, in conjunction with limited contemporary
synthetic approach to such systems prompted us to elaborate compounds 3a-d via palladium-
catalyzed Suzuki-Miyaura cross-coupling with arylboronic acids as coupling partners. As a
reference starting point for exploration, we subjected compound 3a to phenylboronic acid (1.2
equiv.) in the presence of dichlorobis(triphenylphosphine)palladium(II) (PdCl2(PPh3)2) as Pd(0)
source and potassium carbonate as a base in N,N-dimethylformamide-water (4/1, v/v). The
reaction was however unsuccessful due to formation of complex mixtures. We opted for the use of
2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl (Xphos) as a ligand to coordinate with
Bull. Chem. Soc. Ethiop. 2014, 28(1)

Synthesis of 2,6,8-triarylquinazolin-4-ones
83
palladium and increase its electron density and, in turn, accelerate the oxidative addition and
reductive elimination steps in the catalytic cycle [23]. Compound 3a was subjected to
phenylboronic acid (1.2 equiv.) in the presence of PdCl2(PPh3)2-Xphos catalyst complex and
potassium carbonate as a base in DMF under reflux and the starting material was consumed within
3 h (tlc monitoring). 1H NMR spectroscopic analysis of the crude product revealed the presence of
a mixture of the diarylated quinazolin-4(1H)-one and the dehydrogenated starting material.
However, these compounds could not be separated by column chromatography due to similar Rf
values. Non-selectivity to afford double coupled derivatives has been previously observed with
Suzuki-Miyaura cross-coupling of the analogous 2-aryl-6,8-dibromoquinolin-4(1H)-ones with
arylboronic acids [24]. Likewise, the Heck reaction of the analogous 6,8-dibromoflavone with
methyl acrylate afforded mixture of both 6- and 8-monosubstituted and 6,8-disubstituted flavones
[25]. To ensure exhaustive multiple coupling in cases where it is difficult or not possible to control
the selectivity of cross coupling of halogenated heterocycles bearing similar halogen atoms on the
fused benzo ring, an excess of the arylboronic acid is often employed to drive the reaction to
completion [26]. A similar strategy was also employed before by Zhang et al. on 8-bromo-6-
chloroquinoline with excess of bis(pinacolato)diboron (2.2 equiv.) and phenylbromide to afford
6,8-diphenylquinoline in 94% yield [27]. In analogy with these literature precedents, we subjected
3a to phenylboronic acid (2.2 equiv.) using PdCl2(PPh3)2-Xphos catalyst complex and potassium
carbonate as a base in aqueous DMF at 120 °C. We isolated after 2 h by column chromatography
over silica gel the cross-coupled products 4a (70%) and traces of its dehydrogenated derivative.
The use of aqueous dioxane as solvent, on the other hand, afforded 4a (77%) without traces of the
dehydrogenated cross-coupled product. These reaction conditions were extended to substrates 3b-
d with phenylboronic and 4-fluorophenylboronic acids (2.2 equiv.) as coupling partners to afford
the cross-coupled products 4a-h in appreciable yields and high purity without the need for column
chromatography (Scheme 3).
O
O
H
H
Br
Ar
(i)
N
N
N
H
C6H4R
N
H
C6H4R
Br
Ar
4a-h
3a-d
R
Ar
% Yield 4
4a
4b
4c
4d
4e
4f
4-H
4-F
4-Cl
4-OMe
4-H
4-F
4-Cl
4-OMe
C6H5-
C6H5-
C6H5-
C6H5-
4-FC6H4-
4-FC6H4-
4-FC6H4-
4-FC6H4-
77
83
90
80
83
91
86
85
4g
4h
Reagents and conditions: (i) ArB(OH)2 (2.2 equiv.), PdCl2(PPh3)2, Xphos, K2CO3, DMF-water (4/1, v/v), 120
°C, 2 h.
Scheme 2. Suzuki-Miyaura cross-coupling of 3a-d with arylboronic acids.
The heterocyclic ring of the 2,3-dihydroquinazolin-4(1H)-ones has been found to undergo a
different degree of unsaturation through dehydrogenation or aromatization to afford the potentially
tautomeric quinazolin-4(3H)-ones or their quinazoline derivatives [28-32]. Quinazolin-4(3H)-ones
are versatile building blocks in the synthesis of novel 2,3-disubstituted quinazolinones [28-31] and
their 2,4-disubstituted quinazoline derivatives using the principles of lactam-lactim dynamic
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Malose J. Mphahlele et al.
equilibrium phenomena [32]. Oxidants such as KMnO4 [28], CuCl2 [29], DDQ [30] and MnO2
[31] have been employed before in stoichiometric or large excess to convert the 2,3-
dihydroquinazolin-4(1H)-ones into their quinazolin-4(3H)-one derivatives. In this investigation,
we opted for the use of molecular iodine which has been used before as an oxidant to effect the
oxidative aromatization of α,β-unsaturated cyclic compounds and the analogous 2,3-
dihydroquinolin-4(1H)-ones [24]. Compounds 4a-h were subjected to molecular iodine (2 equiv.)
in ethanol under reflux for 2 h and we isolated the potentially tautomeric quinazolin-4(3H)-ones
5a-h in high yield and purity without the need for column chromatography (Scheme 2). Their N-
1
4(3H)-oxo nature was confirmed by the absence of the N-1 and C-2 proton signals in their H
NMR spectra and the significant downfield shift of the N-3 proton signal to δ ca. 12.35 ppm. The
analogous 2-arylquinazolin-4(3H)-one derivatives bearing an aryl group at the 6-position of the
fused benzo ring have been found to serve as orally available ghrelin receptor anatagonists for the
treatment of diabetes and obesity [33].
O
O
OH
H
Ar
Ar
Ar
(i)
H
N
N
N
N
H
C6H4R
N
C6H4R
N
C6H4R
Ar
Ar
Ar
4a-h
5' (iminol)
5a-h (lactam)
R
Ar
%Yield 5
5a
5b
5c
5d
5e
5f
4-H
4-F
4-Cl
4-OMe
4-H
4-F
C6H5-
C6H5-
C6H5-
C6H5-
4-FC6H4-
4-FC6H4-
4-FC6H4-
4-FC6H4-
74
87
71
94
87
89
76
96
5g
5h
4-Cl
4-OMe
Reagents and conditions: (i) I2 (2 equiv.), ethanol, reflux, 2 h.
Scheme 3. Iodine/ethanol–promoted dehydrogenation of 4a-h.
In summary, the results of this investigation demonstrate that anthranilamide readily undergoes
bromination to afford 2-amino-3,5-dibromobenzamide in high yield and purity without affecting
the amide nitrogen. Palladium-mediated Suzuki-Miyaura cross-coupling of the 2-aryl-6,8-
dibromo-2,3-dihydroquinazolin-4(1H)-ones derived from 2-amino-3,5-dibromobenzamide and
arylaldehydes occurs without selectivity to afford novel 2,6,8-triaryl-2,3-dihydroquinazolin-4(1H)-
ones. Iodine-mediated dehydrogenation of the latter afforded the corresponding potentially
tautomeric 2-arylquinazolin-4(3H)-ones, which are potential building blocks for the synthesis of
novel 2,3-disubstituted quinazolinones and their 2,4-disubstituted quinazoline derivatives using
the principles of lactam-lactim dynamic equilibrium phenomena. Moreover, aromatization of the
quinazolin-4(3H)-ones with POCl3 followed by substitution with heteroatom-containing (N, O, S)
nucleophiles or cross-coupling would afford novel polysubstituted quinazolines with potential
biological or photophysical properties.
EXPERIMENTAL
Melting points were recorded on a Thermocouple digital melting point apparatus and are
uncorrected. IR spectra were recorded as powders using a Bruker VERTEX 70 FT-IR
Spectrometer with a diamond ATR (attenuated total reflectance) accessory by using the thin-film
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Synthesis of 2,6,8-triarylquinazolin-4-ones
85
method. For column chromatography, Merck kieselgel 60 (0.063–0.200 mm) was used as
stationary phase. NMR spectra were obtained as DMSO-d6 solutions using Varian Mercury 300
MHz NMR spectrometer and the chemical shifts are quoted relative to the solvent peaks. High-
resolution mass spectra were recorded at the University of Stellenbosch Mass Spectrometry Unit
using Synapt G2 Quadrupole Time-of-flight mass spectrometer.
Synthesis of 2-amino-3,5-dibromobenzamide (2)
A
mixture of 2-aminobenzamide/anthranilamide (1) (10.00 g, 73.4 mmol) and N-
bromosuccinimide (26.37 g, 148.2 mmol) in chloroform-carbon tetrachloride mixture (3/2, v/v;
400 mL) was stirred at room temperature for 3 h. The resulting precipitate was filtered dry on a
sintered funnel to afford (2) (17.93 g, 83%), m.p. 216–217 ºC (Lit. [18] 214–215 ºC); IR (ATR):
νmax = 757, 803, 1129, 1239, 1386, 1450, 1567, 1640, 3180, 3326, 3367, 3423 cm-1; 1H NMR: δ =
6.80 (brs, 2H), 7.46 (br s, 1H), 7.73 (d, J 2.4 Hz, 1H), 7.78 (d, J 2.4 Hz, 1H), 8.05 (brs, 1H); 13
C
NMR: δ = 105.4, 110.9, 117.3, 131.2, 137.2, 146.5, 169.7; HRMS (ESI): m/z [M+H]+ calculated
+
for C7H7N2O79Br2 : 292.8925; found: 292.8928.
Typical procedure for the synthesis of 2-aryl-6,8-dibromo-2,3-dihydroquinazolin-4(1H)-ones 3a-
d.
A mixture of 2 (1 equiv.), benzaldehyde derivative (1.0 equiv.) and boric acid (0.2 equiv.) in a
crucible was homogenized with a mortar and then transferred to a round-bottomed flask. The
mixture was heated at 120 ºC with a heat gun for 5 min. The resultant solid was quenched with an
ice-cold water and then filtered on a sintered funnel. The crude product was recrystallized from
ethanol to afford 3 as a solid. The following products were prepared in this fashion.
6,8-Dibromo-2-phenyl-2,3-dihydroquinazolin-4(1H)-one (3a). A mixture of 2 (2.00 g, 6.82
mmol), benzaldehyde (0.72 g, 6.82 mmol) and boric acid (0.08 g, 1.36 mmol) afforded 3a (2.26 g,
87%), m.p. 198–200 ºC; IR (ATR): νmax = 743, 778, 1104, 1367, 1486, 1598, 1679, 3173, 3380
1
cm-1; H NMR: δ = 5.78 (t, J 3.6 Hz, 1H), 7.24 (d, J 3.3 Hz, 1H), 7.429–7.41 (m, 5H), 7.68 (d, J
2.1 Hz, 1H), 7.80 (d, J 2.1 Hz, 1H), 8.89 (d, J 3.3 Hz, 1H); 13C NMR: δ = 65.2, 108.3, 109.3,
118.4, 126.4, 128.7, 128.9, 129.7, 138.3, 142.7, 143.9, 161.6; HRMS (ESI): m/z [M+H]+
+
calculated for C14H11N2O79Br2 : 380.9238; found: 380.9242.
6,8-Dibromo-2-(4-fluorophenyl)-2,3-dihydroquinazolin-4(1H)-one (3b). A mixture of 2 (2.00 g,
6.82 mmol), 4-fluorobenzaldehyde (0.84 g, 6.82 mmol) and boric acid (0.08 g, 1.36 mmol)
afforded 3b (2.21 g, 82%), m.p. 208–210 ºC; IR (ATR): νmax = 718, 850, 876, 1155, 1231, 1487,
1
1599, 1686, 3181, 3374 cm-1; H NMR: δ = 5.79 (t, J 3.6 Hz, 1H), 7.24 (d, J 3.3 Hz, 1H), 7.20 (t,
J 8.7 Hz, 2H), 7.42 (t, J 8.7 Hz, 2H), 7.69 (d, J 2.1 Hz, 1H), 7.81 (d, J 2.1 Hz, 1H), 8.88 (d, J 3.3
2
3
Hz, 1H); 13C NMR: δ = 64.8, 108.5, 109.3, 115.7 (d, JCF Hz), 118.3, 128.6 (d, JCF 21.7 Hz),
4
1
129.8, 138.4, 138.8 (d, JCF 3.0 Hz), 143.8, 161.5, 162.4 (d, JCF 242.4 Hz); HRMS (ESI): m/z
[M+H]+ calculated for C14H10N2OF79Br2 : 396.8987; found: 396.8969.
+
6,8-Dibromo-2-(4-chlorophenyl)-2,3-dihydroquinazolin-4(1H)-one (3c). A mixture of 2 (2.00 g,
6.82 mmol), 4-chlorobenzaldehyde (0.96 g, 6.82 mmol) and boric acid (0.08 g, 1.36 mmol)
afforded 3c (2.54 g, 90%), m.p. 237–238 ºC; IR (ATR): νmax = 788, 823, 896, 946, 1085, 1142,
1360, 1420, 1481, 1596, 1671, 3182, 3362 cm-1; 1H NMR: δ = 5.78 (t, J 3.6 Hz, 1H), 7.24 (d, J 3.3
Hz, 1H), 7.40 (d, J 9.0 Hz, 2H), 7.44 (d, J 9.0 Hz, 2H), 7.67 (d, J 2.1 Hz, 1H), 7.80 (d, J 2.1 Hz,
1H), 8.90 (d, J 3.3 Hz, 1H); 13C NMR: δ = 64.7, 108.5, 109.4, 118.3, 128.4, 128.9, 129.8, 133.4,
+
138.4, 141.6, 143.8, 161.5. HRMS (ESI): m/z [M+H]+ calculated for C14H10N2O35Cl79Br2 :
412.8692; found: 412.8676.
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Malose J. Mphahlele et al.
6,8-Dibromo-2-(4-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one (3d). A mixture of 2 (2.00 g,
6.82 mmol), 4-methoxybenzaldehyde (0.93 g, 6.82 mmol) and boric acid (0.08 g, 1.36 mmol)
afforded 3d (2.40 g, 86 %), m.p. 195–197 ºC; IR (ATR): νmax = 759, 779, 1033, 1119, 1206, 1512,
1
1676, 3181, 3381 cm-1; H NMR: δ = 3.71 (s, 3H), 5.73 (t, J 3.3 Hz, 1H), 6.91 (d, J 8.7 Hz, 2H),
7.09 (d, J 2.7 Hz, 1H), 7.30 (d, J 8.7 Hz, 2H), 7.68 (d, J 2.1 Hz, 1H), 7.79 (d, J 2.1 Hz, 1H), 8.22
(d, J 3.3 Hz, 1H); 13C NMR: δ = 55.6, 64.9, 108.2, 109.3, 114.2, 118.4, 127.7, 129.7, 134.6, 138.4,
+
143.9, 159.6, 161.7; HRMS (ESI): m/z [M+H]+ calculated for C15H13N2O279Br2 : 408.9187; found:
408.9192.
Typical procedure for the Suzuki-Miyaura cross-coupling of 3a-d with arylboronic acids
2-Aryl-6,8-dibromoquinazolin-4(1H)-one 3 (1 equiv.), arylboronic acid (2.5 equiv.), PdCl2(PPh3)2
(5% of 3), Xphos (10% of 3), K2CO3 (2 equiv.) and DMF-water (4/1, v/v; ca. 5 mL/mmol of 3)
were added to a two-necked flask equipped with a stirrer bar, rubber septum and a condenser. The
mixture was flushed for 20 min with argon gas and a balloon filled with an argon gas was
connected to the top of the condenser. The mixture was heated with stirring at 120 °C under an
argon atmosphere for 3 hours and then cooled to room temperature. The cooled mixture was
poured into an ice-cold water and the precipitate was filtered on a sintered funnel. The solid
product was taken-up into chloroform and the solution was washed twice with brine. The organic
phase was dried over MgSO4, filtered and then evaporated under reduced pressure. The product
was recrystallized from ethanol to afford the 2,6,8-triarylquinazolin-4(1H)-one 4. The following
products were prepared in this fashion.
2,6,8-Triphenylquinazolin-4(1H)-one (4a). A mixture of 3a (1.00 g, 2.61 mmol), phenylboronic
acid (0.699 g, 5.74 mmol), PdCl2(PPh3)2 (0.092 g, 0.313 mmol), Xphos (0.125 g, 0.263 mmol) and
K2CO3 (0.725 g, 5.26 mmol) in DMF-water (20 mL) afforded 4a (0.750 g, 77%), m.p. 215–217
°C; IR (ATR): νmax = 697, 760, 1274, 1381, 1573, 1680, 3050, 3173, 3384 cm-1; 1H NMR: δ = 5.70
(t, J 3.0 Hz, 1H), 6.50 (d, J 3.0 Hz, 1H), 7.26–7.53 (m, 14H), 7.62 (d, J 7.5 Hz, 2H), 7.95 (d, J 3.0
Hz, 1H), 8.65 (d, J 3.0 Hz, 1H); 13C NMR: δ = 65.5, 116.9, 125.3, 126.3, 126.6, 127.1, 128.2,
128.4, 128.5, 128.8, 129.3, 129.4, 129.5, 129.7, 133.0, 138.0, 140.0, 143.2, 143.6, 163.7; HRMS
(ESI): m/z [M+H]+ calculated for C26H21N2O+: 377.1654; found: 377.1651.
2-(4-Fluorophenyl)-6,8-diphenylquinazolin-4(1H)-one (4b). A mixture of 3b (1.00 g, 2.49 mmol),
phenylboronic acid (0.67 g, 5.47 mmol), PdCl2(PPh3)2 (0.090 g, 0.125 mmol), Xphos (0.120 g,
0.250 mmol) and K2CO3 (0.690 g, 5.02 mmol) in DMF-water (20 mL) afforded 4b (0.810 g, 83%),
m.p. 198–200 °C; IR (ATR): νmax = 684, 699, 760, 890, 1155, 1235, 1465, 1519, 1613, 1652,
1
3156, 3392 cm-1; H NMR: δ = 5.71 (t, J 3.0 Hz, 1H), 6.51 (d, J 2.4 Hz, 1H), 7.19 (t, J 8.7 Hz,
2H), 7.25 (t, J 7.5 Hz, 1H), 7.38–7.53 7 (m, 10H), 7.62 (d, J 7.5 Hz, 2H), 7.97 (d, J 2.4 Hz, 1H),
2
8.66 (d, J 3.0 Hz, 1H). 13C NMR: δ = 65.0, 115.6 (d, JCF 21.4 Hz), 116.8, 125.3, 126.3, 127.2,
3
4
128.2, 128.6, 128.7, 128.8, 129.4 (d, JCF 8.3 Hz), 129.5, 129.8, 133.1, 138.0, 139.3 (d, JCF 2.8
Hz), 139.9, 143.5, 162.3 (d, JCF 242.3 Hz), 163.7; HRMS (ESI): m/z [M+H]+ calculated for
1
C26H20N2FO+: 395.1555; found: 395.1555.
2-(4-Chlorophenyl)-6,8-diphenylquinazolin-4(1H)-one (4c). A mixture of 3c (1.00 g, 2.41 mmol),
phenylboronic acid (0.650 g, 5.32 mmol), PdCl2(PPh3)2 (0.084 g, 0.122 mmol), Xphos (0.114 g,
0.241 mmol) and K2CO3 (0.672 g, 4.87 mmol) in DMF-water (20 mL) afforded 4c (0.900 g, 90%),
m.p. 199–201 °C; IR (ATR): νmax = 697, 756, 1060, 1287, 1318, 1506, 1656, 3097, 3421 cm-1; 1H
NMR: δ = 5.69 (t, J 3.0 Hz, 1H), 6.56 (s, 1H), 7.26 (t, J 7.5 Hz, 1H), 7.38–7.60 (m, 12H), 7.62 (d,
J 8.4 Hz, 2H), 7.95 (s, 1H), 8.67 (d, J 3.0 Hz, 1H); 13C NMR: δ = 64.9, 116.8, 125.3, 126.3, 127.2,
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Synthesis of 2,6,8-triarylquinazolin-4-ones
87
128.2, 128.6 (2xC), 128.8, 129.2, 129.3, 129.4, 129.5, 129.8, 133.1, 138.0, 139.9, 142.2, 143.4,
163.7; HRMS (ESI): m/z [M+H]+ calculated for C26H20N235ClO+: 411.1264; found: 411.1260.
6,8-Diphenyl-2-(4-methoxyphenyl)quinazolin-4(1H)-one (4d). A mixture of 3d (1.00 g, 2.66
mmol), phenylboronic acid (0.710 g, 5.85 mmol), PdCl2(PPh3)2 (0.086 g, 0.122 mmol), Xphos
(0.126 g, 0.266 mmol) and K2CO3 (0.672 g, 4.87 mmol) in DMF-water (20 mL) afforded 4d
(0.860 g, 80%), m.p. 218–219 °C; IR (ATR): νmax = 692, 1058, 1188, 1444, 1606, 1654, 3241,
3390 cm-1; 1H NMR: δ = 3.71 (s, 3H), 5.66 (t, J 3.0 Hz, 1H), 6.34 (d, J 3.0 Hz, 1H), 6.90 (d, J 8.7
Hz, 2H), 7.28 (t, J 7.5 Hz, 1H), 7.33 (d, J 8.7 Hz, 2H), 7.38–7.53 (m, 8H),7.62 (d, J 7.5 Hz, 2H),
7.96 (d, J 3.0 Hz, 1H), 8.58 (d, J 3.0 Hz, 1H); 13C NMR: δ = 55.6, 65.2, 114.1, 116.9, 125.3,
126.3, 127.1, 127.9, 128.1, 128.4, 129.3, 129.4, 129.5, 129.7, 132.9, 125.0, 138.0, 140.0, 143.6,
+
159.5, 163.8; HRMS (ESI): m/z [M+H]+ calculated for C27H23N2O2 : 407.1760; found: 407.1758.
6,8-Bis(4-fluorophenyl)-2-phenylquinazolin-4(1H)-one (4e). A mixture of 3a (1.00 g, 2.63 mmol),
4-fluorophenylboronic acid (0.81 g, 5.76 mmol), PdCl2(PPh3)2 (0.092 g, 0.130 mmol), Xphos
(0.125 g, 0.263 mmol) and K2CO3 (0.726 g, 5.26 mmol) in DMF-water (20 mL) afforded 4e (0.90
g, 83%), m.p. 312–315 °C; IR (ATR): νmax = 696, 797, 834, 1211, 1601, 1666, 3068, 3165, 3369
cm-1; 1H NMR: δ = 5.68 (t, J 3.3 Hz, 1H), 6.55 (d, J 2.4 Hz, 1H), 7.22 (t, J 8.7 Hz, 2H), 7.28–7.41
1 (m, 7H), 7.46 (d, J 2.1 Hz, 1H), 7.49 (t, J 8.7 Hz, 2H), 7.65 (t, J 8.7 Hz, 2H), 7.93 (d, J 2.1 Hz,
1H), 8.63 (s, 1H); 13C NMR (75 MHz, DMSO-d6): δ = 65.5, 116.1 (d, 2JCF 21.1 Hz), 116.3 (d, 2JCF
21.3 Hz), 116.9, 125.3, 126.6, 127.5, 128.3 (d, 3JCF 8.0 Hz), 128.5, 128.7, 128.8, 131.5 (d, 3JCF 8.3
4
4
1
Hz), 133.0, 134.3 (d, JCF 3.2 Hz), 136.4 (d, JCF 3.0 Hz), 143.1, 143.7, 161.8 (d, JCF 242.0 Hz),
162.2 (d, JCF 242.5 Hz), 163.6; HRMS (ESI): m/z [M+H]+ calculated for C26H19N2OF2+:
1
413.1465; found: 413.1463.
2,6,8-Tris(4-fluorophenyl)quinazolin-4(1H)-one (4f). A mixture of 3b (1.00 g, 2.51 mmol), 4-
fluorophenylboronic acid (0.77 g, 5.52 mmol), PdCl2(PPh3)2 (0.088 g, 0.125 mmol), Xphos (0.119
g, 0.251 mmol) and K2CO3 (0.693 g, 5.02 mmol) in DMF-water (20 mL) afforded 4f (0.990 g,
91%), m.p. 265–267 °C; IR (ATR): νmax = 794, 874, 1213, 1377, 1485, 1604, 1667, 3055, 3171,
3370 cm-1; 1H NMR: δ = 5.69 (t, J 3.3 Hz, 1H), 6.56 (d, J 2.4 Hz, 1H), 7.18 (t, J 8.7 Hz, 2H), 7.21
(t, J 8.7 Hz, 2H), 7.32 (t, J 8.7 Hz, 2H), 7.43 (t, J 8.7 Hz, 2H), 7.46 (d, J 2.1 Hz, 1H), 7.49 (t, J 8.7
Hz, 2H), 7.66 (t, J 8.7 Hz, 2H), 7.92 (d, J 2.1 Hz, 1H), 8.64 (d, J 2.7 Hz, 1H); 13C NMR: δ = 65.1,
115.6 (d, 2JCF 21.4 Hz), 116.1 (d, 2JCF 21.4 Hz), 116.3 (d, 2JCF 21.4 Hz), 116.8, 125.3, 127.7, 128.3
(d, 3JCF 8.0 Hz), 128.8, 128.9 (d, 3JCF 8.3 Hz), 131.6 (d, 3JCF 8.3 Hz), 133.1, 134.2 (d, 4JCF 3.2 Hz),
136.4 (d, 4JCF 3.2 Hz), 139.2 (d, 4JCF 3.0 Hz), 143.6, 161.9 (d, 1JCF 242.2 Hz), 162.3 (d, 1JCF 242.8
Hz), 162.3 (d, JCF 242.5 Hz), 163.6; HRMS (ESI): m/z [M+H]+ calculated for C26H18N2OF3+:
1
431.1371; found: 431.1372.
2-(4-Chlorophenyl)-6,8-bis(4-fluorophenyl)quinazolin-4(1H)-one (4g). A mixture of 3c (1.00 g,
2.41 mmol), 4-fluorophenylboronic acid (0.745 g, 5.32 mmol), PdCl2(PPh3)2 (0.084 g, 0.121
mmol), Xphos (0.114 g, 0.241 mmol) and K2CO3 (0.672 g, 4.87 mmol) in DMF-water (20 mL)
afforded 4g (0.93 g, 86%), m.p. 326–328 °C; IR (ATR): νmax = 790, 825, 1089, 1222, 1482, 1609,
1
1673, 3065, 3166, 3372 cm-1; H NMR (300 MHz, DMSO-d6): δ = 5.68 (t, J 3.3 Hz, 1H), 6.62 (d,
J 3.3 Hz, 1H), 7.22 (t, J 8.7 Hz, 2H), 7.33 (t, J 8.7 Hz, 2H), 7.41 (s, 4H), 7.46 (d, J 2.1 Hz, 1H),
7.48 (t, J 8.7 Hz, 2H), 7.65 (t, J 8.7 Hz, 2H), 7.93 (d, J 2.1 Hz, 1H), 8.67 (s, 1H); 13C NMR (75
MHz, DMSO-d6): δ = 65.0, 116.1 (d, 2JCF 21.3 Hz), 116.3 (d, 2JCF 21.1 Hz), 116.8, 125.3, 128.3 (d,
3
4
3JCF 8.0 Hz), 128.7, 128.8, 128.9, 131.6 (d, JCF 8.0 Hz), 133.2, 134.2 (d, JCF 3.0 Hz), 136.4 (d,
4JCF 3.1 Hz), 136.1, 136.4 (d, JCF 21.3 Hz), 142.1, 143.6, 161.9 (d, JCF 241.9 Hz), 162.3 (d, JCF
242.7 Hz), 163.6; HRMS (ESI): m/z [M+H]+ calculated for C26H18N2OF235Cl+: 447.1076; found:
447.1077.
1
1
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Malose J. Mphahlele et al.
6,8-Bis(4-fluorophenyl)-2-(4-methoxyphenyl)quinazolin-4(1H)-one (4h). A mixture of 3d (1.00 g,
2.44 mmol), 4-fluorophenylboronic acid (0.75 g, 5.36 mmol), PdCl2(PPh3)2 (0.085 g, 0.122
mmol), Xphos (0.116 g, 0.244 mmol) and K2CO3 (0.674 g, 4.88 mmol) in DMF-water (20 mL)
afforded 4h (0.92 g, 85%), m.p. 230–232 °C; IR (ATR): νmax = 797, 831, 1024, 1217, 1445, 1606,
1
1654, 3249, 3375 cm-1; H NMR: δ = 3.71 (s, 3H), 5.63 (t, J 3.3 Hz, 1H), 6.44 (d, J 3.3 Hz, 1H),
6.90 (d, J 8.7 Hz, 2H), 7.22 (t, J 8.7 Hz, 2H), 7.31 (d, J 8.7 Hz, 2H), 7.32 (t, J 8.7 Hz, 2H), (d, J
3.0 Hz, 1H), 7.45 7.31 (t, J 8.7 Hz, 2H), 7.66 (t, J 8.7 Hz, 2H), 7.92 (d, J 3.0 Hz, 1H), 8.57 (d, J
2
2
3.0 Hz, 1H); 13C NMR: δ = 56.0, 65.3, 114.1, 116.1 (d, JCF 21.3 Hz), 116.3 (d, JCF 21.1 Hz),
3
3
116.9, 125.3, 127.6, 128.0, 128.3 (d, JCF 8.0 Hz), 128.7, 131.5 (d, JCF 8.0 Hz), 133.0, 134.3 (d,
4JCF 3.1 Hz), 135.0, 136.4 (d, JCF 3.2 Hz), 143.8, 159.5, 161.9 (d, JCF 241.9 Hz), 162.2 (d, JCF
242.8 Hz), 163.7; HRMS (ESI): m/z [M+H]+ calculated for C27H21N2O2F2+: 443.1574; found:
443.1578.
4
1
1
Typical procedure for the iodine-ethanol–promoted dehydrogenation of 4a-h
A stirred mixture of the 2,6,8-triaryl-2,3-dihydroquinazolin-4(1H)-one 4 (1 equiv.) and iodine (2
equiv.) in ethanol (15 mL per mmol of 4) was refluxed for 60 min. The mixture was allowed to
cool to room temperature and then quenched with saturated sodium thiosulfate solution. The
resulting precipitate was filtered on a sintered funnel, washed with cold ethanol and dried under
reduced pressure to afford the corresponding quinazolin-4(3H)-one 5. The following products
were prepared in this fashion.
2,6,8-Triphenylquinazolin-4(3H)-one (5a). A mixture of 4a (0.76 g, 2.01 mmol) and iodine (1.02
g, 4.02 mmol) in ethanol (30 mL) afforded 5e (0.56 g, 74%), m.p. 318–320 °C; IR (ATR): νmax
=
658, 759, 1291, 1598, 1652, 3152, 3302 cm-1; 1H NMR: δ = 7.42–7.56 (m, 9H), 7.84 (d, J 7.8 Hz,
2H), 7.88 (d, J 7.8 Hz, 2H), 8.14 (s, 2H), 8.16 (d, J 3.0 Hz, 1H), 8.41(s, 1H), 12.71 (s, 1H); 13C
NMR: δ = 127.6, 128.2, 132.4, 132.9, 133.2, 133.3, 133.5, 134.1, 134.7, 136.2, 136.9, 138.3,
138.9, 143.4, 143.7, 144.3, 144.9, 150.5, 156.7, 168.1; HRMS (ESI): m/z [M+H]+ calculated for
C26H19N2O+: 375.1497; found: 375.1502.
2-(4-Fluorophenyl)-2,8-diphenylquinazolin-4(3H)-one (5b). A mixture of 4b (1.36 g, 3.59 mmol)
and iodine (1.82 g, 7.18 mmol) in ethanol (30 mL) afforded 5c (1.18 g, 87%), m.p. 308–309 °C;
1
IR (ATR): νmax = 686, 759, 893, 1233, 1601, 1667, 3055, 3162 cm-1; H NMR: δ = 7.36 (t, J 7.8
Hz, 2H), 7.44 (t, J 7.5 Hz, 2H), 7.52 (t, J 7.5 Hz, 4H), 7.81 (d, J 7.8 Hz, 2H), 7.85 (d, J 7.8 Hz,
2H), 8.11 (d, J 3.0 Hz, 1H), 8.19 (d, J 7.8 Hz, 2H), 8.39 (d, J 3.0 Hz, 1H), 12.70 (s, 1H); 13C
2
4
NMR: δ = 116.2 (d, JCF 21.7 Hz), 122.5, 123.1, 127.4, 127.9, 128.3, 128.5, 129.6, 129.8 (d, JCF
3
2.9 Hz), 130.7 (d, JCF 9.0 Hz), 131.1, 133.9, 138.4, 138.7, 139.3, 139.8, 145.4, 150.8, 163.0 (d,
1JCF 248.1 Hz), 163.1; HRMS (ESI): m/z [M+H]+ calculated for C26H18N2OF+: 392.1407; found:
392.1411.
2-(4-Chlorophenyl)-6,8-diphenylquinazolin-4(3H)-one (5c). A mixture of 4c (0.74 g, 1.79 mmol)
and iodine (0.91 g, 3.58 mmol) in ethanol (30 mL) afforded 5c (0.52 g, 71%), m.p. 313–315 °C;
1
IR (ATR): νmax = 677, 754, 804, 839, 1597, 1669, 3081, 3156 cm-1; H NMR: δ = 7.42–7.56 (m,
8H), 7.81 (d, J 7.8 Hz, 2H), 7.88 (d, J 7.8 Hz, 2H), 8.14 (d, J 7.8 Hz, 2H), 8.15 (s, 1H), 8.41 (d, J
3.0 Hz, 1H), 12.77 (s, 1H); 13C NMR: δ = 122.7, 123.2, 127.4, 127.9, 128.3, 128.5, 129.2, 129.7,
130.0, 131.2, 132.6, 133.8, 136.6, 138.4, 138.8, 139.4, 139.8, 145.6, 151.4, 163.5; HRMS (ESI):
m/z [M+H]+ calculated for C26H18N2O35Cl +: 409.1108; found: 409.1092.
6,8-Diphenyl-2-(4-methoxyphenyl)quinazolin-4(3H)-one (5d). A mixture of 4d (0.90 g, 1.81
mmol) and iodine (0.91 g, 3.62 mmol) in ethanol (30 mL) afforded 5d (0.85 g, 94%), m.p. 307–
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Synthesis of 2,6,8-triarylquinazolin-4-ones
89
309 °C; IR (ATR): νmax = 698, 763, 1248, 1594, 1665, 3036, 3160 cm-1; 1H NMR: δ = 3.83 (s, 3H),
7.07 (d, J 7.8 Hz, 2H), 7.44 (t, J 7.8 Hz, 2H), 7.51 (d, J 7.8 Hz, 2H), 7.54 (d, J 7.8 Hz, 2H), 7.82
(d, J 7.8 Hz, 2H), 7.86 (d, J 7.8 Hz, 2H), 8.13 (d, J 3.0 Hz, 1H), 8.15 (d, J 7.8 Hz, 2H), 8.39 (d, J
3.0 Hz, 1H), 12.97 (s, 1H); 13C NMR: δ = 56.0, 114.6, 122.3, 123.1, 125.4, 127.4, 127.9, 128.3,
128.4, 129.7, 129.9, 131.2, 133.9, 138.0, 138.8, 139.4, 139.6, 145.7, 151.3, 162.4, 163.1; HRMS
+
(ESI): m/z [M+H]+ calculated for C27H21N2O2 : 405.1603; found: 405.1606.
6,8-Bis(4-fluorophenyl)-2-phenylquinazolin-4(3H)-one (5e). A mixture of 4e (0.70 g, 1.70 mmol)
and iodine (0.87 g, 3.40 mmol) in ethanol (30 mL) afforded 5e (0.61 g, 87%), m.p. 318–320 °C;
1
IR (ATR): νmax = 692, 827, 1158, 1231, 1466, 1507, 1599, 1650, 3147, 3175 cm-1; H NMR: δ =
5.84 (s, 1H), 7.09 (t, J 8.7 Hz, 2H), 7.13 (t, J 8.7 Hz, 2H), 7.36 (d, J 7.5 Hz, 2H), 7.37 (t, J 8.7 Hz,
2H), 7.46 (d, J 7.5 Hz, 2H), 7.47 (d, J 3.0 Hz, 1H), 7.53 (t, J 8.7 Hz, 2H), 8.35 (d, J 3.0 Hz, 1H),
2
2
12.72 (br s, 1H); 13C NMR: δ = 115.1 (d, JCF 21.0 Hz), 116.4 (d, JCF 21.6 Hz), 122.6, 123.2,
128.2, 129.2, 129.6 (d, JCF 8.3 Hz), 131.9, 133.1, 133.2 (d, 3JCF 8.0 Hz), 133.9, 134.9 (d, 4JCF 2.3
Hz), 135.7 (d, JCF 3.0 Hz), 137.4, 138.8, 145.3, 151.8, 162.3 (d, JCF 243.3 Hz), 162.7 (d, JCF
244.2 Hz), 162.9; HRMS (ESI): m/z [M+H]+ calculated for C26H17N2OF2+: 411.1309; found:
411.1313.
3
4
1
1
2,6,8-Tris(4-fluorophenyl)quinazolin-4(3H)-one (5f). A mixture of 4f (0.81 g, 1.87 mmol) and
iodine (0.95 g, 3.74 mmol) in ethanol (30 mL) afforded 5f (0.72 g, 89%), m.p. > 350 °C; IR
(ATR): νmax = 801, 821, 1157, 1231, 1511, 1607, 1676, 3085, 3168, 3467 cm-1; 1H NMR: δ = 7.31
(t, J 8.7 Hz, 2H), 7.32 (t, J 8.7 Hz, 2H), 7.36 (t, J 8.7 Hz, 2H), 7.85 (t, J 8.7 Hz, 2H), 7.90 (t, J 8.7
Hz, 2H), 8.08 (d, J 3.0 Hz, 1H), 8.17 (t, J 8.7 Hz, 2H), 8.35 (d, J 3.0 Hz, 1H), 12.68 (br s, 1H);
2
2
2
13C NMR δ = 115.1 (d, JCF 21.1 Hz), 116.1 (d, JCF 21.6 Hz), 116.4 (d, JCF 21.4 Hz), 122.6,
123.2, 129.5 (d, 3JCF 8.3 Hz), 129.7 (d, 4JCF 2.3 Hz), 130.8 (d, 3JCF 8.8 Hz), 133.2 (d, 3JCF 8.3 Hz),
4
4
1
133.8, 134.8 (d, JCF 3.2 Hz), 135.7 (d, JCF 3.1 Hz), 137.4, 138.7, 145.3, 150.8, 162.2 (d, JCF
242.8 Hz), 162.6 (d, JCF 243.3 Hz), 164.3 (d, JCF 243.3 Hz), 164.6; HRMS (ESI): m/z [M+H]+
1
1
calculated for C26H16N2OF3+: 429.1215; found: 429.1215.
2-(4-Chlorophenyl)-6,8-bis(4-fluorophenyl)quinazolin-4(3H)-one (5g). A mixture of 4g (1.15 g,
2.58 mmol) and iodine (1.31 g, 5.16 mmol) in ethanol (30 mL) afforded 4g (0.87 g, 76%), m.p.
342–344 °C; IR (ATR): νmax = 670, 823, 999, 1096, 1229, 1463, 1506, 1598, 1675, 3387 cm-1; 1H
NMR: δ = 7.33 (t, J 7.8 Hz, 2H), 7.34 (t, J 7.8 Hz, 2H), 7.58 (d, J 7.8 Hz, 2H), 7.87 (t, J 7.8 Hz,
2H), 7.90 (t, J 7.8 Hz, 2H), 8.07 (s, 1H), 8.16 (d, J 7.8 Hz, 2H), 8.35 (s, 1H), 12.54 (br s, 1H); 13
C
2
2
NMR: δ = 115.0 (d, JCF 21.0 Hz), 116.4 (d, JCF 21.3 Hz), 122.7, 123.3, 129.1, 129.5 (d, 3JCF 8.2
3
4
4
Hz), 130.1, 133.1 (d, JCF 8.3 Hz), 133.2, 133.7, 135.2 (d, JCF 3.2 Hz), 136.0 (d, JCF 3.1 Hz),
1
1
136.3, 136.7, 138.4, 145.9, 152.8, 162.2 (d, JCF 242.8 Hz), 162.6 (d, JCF 243.3 Hz), 164.8;
HRMS (ESI): m/z [M+H]+ calculated for C26H16N2OF235Cl+: 445.0919; found: 445.0912.
6,8-Bis(4-fluorophenyl)-2-(4-methoxyphenyl)quinazolin-4(3H)-one (5h). A mixture of 4h (0.73 g,
1.65 mmol) and iodine (0.84 g, 3.30 mmol) in ethanol (30 mL) afforded 5h (0.70 g, 96%), m.p. >
350 °C; IR (ATR): νmax = 801, 818, 830, 1186, 1227, 1227, 1510, 1570, 1595, 1676, 3168 cm-1;
1H NMR: δ = 3.88 (s, 3H), 7.04 (d, J 7.8 Hz, 2H), 7.30 (t, J 8.7 Hz, 2H), 7.12 (t, J 8.7 Hz, 2H),
7.85 (t, J 8.7 Hz, 2H), 7.87 (t, J 8.7 Hz, 2H), 8.10 (d, J 7.8 Hz, 2H), 8.13 (d, J 3.0 Hz, 1H), 8.35
(d, J 3.0 Hz, 1H), 12.56 (s, 1H); 13C NMR: δ = 55.8, 114.5, 114.9 (d, 2JCF 21.1 Hz), 116.3 (d, 2JCF
3
3
21.3 Hz), 122.2, 123.1, 125.3, 129.4 (d, JCF 8.3 Hz), 129.9, 132.0 (d, JCF 8.0 Hz), 133.7, 134.9
(d, 4JCF 3.2 Hz), 135.8 (d, 4JCF 3.0 Hz), 136.9, 138.4, 145.5, 151.3, 162.2 (d, 1JCF 243.0 Hz), 162.3,
162.6 (d, JCF 244.1 Hz), 163.0; HRMS (ESI): m/z [M+H]+ calculated for C27H19N2O2F2+:
1
441.1415; found: 441.1416.
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Malose J. Mphahlele et al.
ACKNOWLEDGEMENTS
The authors are grateful to the University of South Africa for financial assistance. MMM and
TAK thank the Chair of Ecotoxicology Research’s Cultivating Woman Leaders in Sciences
Program for BSc Hon. Research Assistantship.
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Bull. Chem. Soc. Ethiop. 2014, 28(1)

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