Fuctionalization of Linear and Angular Phenothiazine and Phenoxazine Ring Systems via Pd(0)/XPhos Mediated Suzuki-Miyaura Cross-coupling Reactions

Article abstract of DOI:10.1002/jhet.2485

Chloro-substituted phenothiazines and phenoxazines were successfully derivatized with phenylboronic and styrylboronic acids using Suzuki–Miyaura cross-coupling reaction catalyzed by Pd(0)/XPhos for the first time in good yields. The protocol employed 4 mol% Pd and 7 mol% XPhos with K₃PO₄in acetonitrile at 80°C. The reaction condition is compatible with carbonyl and unprotected N–H groups in substrates. Structural assignments were established by combined spectroscopic (UV, IR,¹H, and¹³C NMR), MS, and elemental analytical data.

Full text of DOI:10.1002/jhet.2485

Month 2015
Fuctionalization of Linear and Angular Phenothiazine and Phenoxazine
Ring Systems via Pd(0)/XPhos Mediated Suzuki-Miyaura Cross-coupling
Reactions
c
a
a
b
*
Efeturi A. Onoabedje, Uchechukwu C. Okoro, David W. Knight, and Amitabha Sarkar
aDepartment of Pure and Industrial Chemistry, University of Nigeria, Nsukka, Nigeria
bSchool of Chemistry, Department of Organic Chemistry, Cardiff University, Wales, UK
cDepartment of Organic Chemistry, India Association for the Cultivation of Science, Kolkata 700032, India
*
E-mail: efeturi.onoabedje@unn.edu.ng
Additional Supporting Information may be found in the online version of this article.
Received March 12, 2015
DOI 10.1002/jhet.2485
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
Chloro-substituted phenothiazines and phenoxazines were successfully derivatized with phenylboronic and
styrylboronic acids using Suzuki–Miyaura cross-coupling reaction catalyzed by Pd(0)/XPhos for the first time
in good yields. The protocol employed 4 mol% Pd and 7 mol% XPhos with K3PO4 in acetonitrile at 80°C. The
reaction condition is compatible with carbonyl and unprotected N–H groups in substrates. Structural assignments
were established by combined spectroscopic (UV, IR, 1H, and 13C NMR), MS, and elemental analytical data.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
particular, chlorpromazine, promethazine, and diethazine
were applied as tranquilizers, antihistamines, and for the
treatment of Parkinson disease, respectively [19,20]. In addi-
tion to the physiological activities of phenothiazines and their
derivatives, their reversible oxidative properties, which give
rise to characteristic deep-colored radical cation absorption,
made them attractive spectroscopic probes in molecular
arrangements for photoinduced electron transfer studies and
material scientific motifs [21,22]. Undoubtedly, the analo-
gous phenoxazines also exhibit reversible oxidation charac-
teristics. Reports disclosed that phenoxazine derivatives are
widely applied as organic light-emitting diodes [23–26].
The earliest modification of the structure of the parent com-
pounds 1 and 2 in which benzene rings are fused to the sides
of ring A and/or C results in nonlinear phenothiazine and
phenoxazine rings of which benzo[a]phenothiazine and
benzo[a]phenoxazine 3 and their derivatives were the most
popular ones [27–31].
The ever expanding therapeutic applications of phenothi-
azine 1 and phenoxazine 2 and their derivatives motivated
the investigation of facile reaction protocols for function-
alization of these compounds [1–5].
Phenothiazine and phenoxazine triheterocyclic provide the
basic structures for various classes molecules of pharmaco-
therapeutic agents with a broad spectrum of biological activ-
ity [1,6]. Recent reviews and reports on the progress of
biological activities of various synthesized phenothiazines
revealed that they exhibit promising antibacterial and anti-
fungal [7,8], anticancer [9,10], multidrug resistance reversal
[10,11], anti-inflammatory [12,13], antiviral [3], antimalarial
[3], analgesic [14], and other properties. Interestingly, most
of the activities of phenothiazine are closely exhibited by
phenoxazine and its derivatives. For example, novel water
soluble 2-amino-4,4α,7-dimethyl-3H-phenoxazine was re-
ported to possess antiproliferative, immunosuppressive,
antibacterial, antiviral [15,16], and antimalarial effects. In
addition, multidrug resistance modulator in cancer cell of
phenoxazines has been reported in several papers [17,18].
Previously, phenothiazine group of drugs was known as
antipsychotic drugs and phenothiazine derivatives, and in
Classical chemical methods have been employed in the
syntheses of phenothiazine and phenoxazine derivatives.
However, the application of transition metal-catalyses is
largely unexplored in spite of its popularity in C–C bond
formation in the recent time because of their mild reaction
© 2015 HeteroCorporation

E. A. Onoabedje, U. C. Okoro D. W. Knight, and A. Sarkar
Vol 000
conditions. Moreover, the attention of the synthetic commu-
nity has been drawn to the inclusion of chloroarenes and
heterochloroarenes as coupling partners in palladium-
catalyzed cross-coupling reactions because they are
economically cheaper, easily available [32–34], and are
pharmacophores in wide range of drugs [15,16,35]. To this
end, several electron-rich and bulky ligands such as
dialkylbiarylphosphines [36–38], N-heterocyclic carbenes
[39–41], ferrocenyl dialkyl phosphene [42], and others have
been developed to facilitate otherwise slow oxidative addition
of aryl chlorides and to circumvent the potential binding of
heterocyclic substrates to metal center in the catalyst. How-
ever, chlorophenothiazine and chlorophenoxazine that are rel-
atively less expensive and easily available have rarely been
used. Previously reported applications of Suzuki–Miyaura
cross-coupling reactions involved the cross-coupling of
organo boronic acid or its ester with aryl chlorides [43] or
chloroquinolines [44]. Muller and coworkers described the
functionalization of bromophenothiazines via Pd-catalyzed
standard Suzuki coupling in several of their papers but not
chlorophenothiazines [22,45–47]. Therefore, a convenient
protocol for the transformation of chlorophenothiazines and
chlorophenoxazines is described. To our knowledge, this is
the first time this protocol is reported with these classes of
substrates.
system in combination with either of the bases, Na2CO3,
K2CO3, or K3PO4, and aqueous polar solvents. The prelim-
inary experiment was conducted by reacting 2-chloro-10H-
phenothiazine with styryl boronic acid to afford 2-styryl-
10H-phenothiazine 9. This reaction employed Pd(OAc)2
(2 mol%), XPhos (4 mol%) and K3PO4 (3 mM) in acetoni-
trile at 80°C. The formation of product was observed in
trace amounts after an hour, which increase with time.
However, after 8 h, there was no noticeable change in
TLC even after the reaction was allowed to run overnight.
The product was isolated with a yield of 53% after work-
up by solvent extraction and purified by flash chromatogra-
phy on silica gel using 5% EtOAc/95% pet ether as eluent.
The spectral and elemental analysis data of the isolated
product were in agreement with molecular formula
C20H15NS and assigned structure. While the 1HNMR spec-
trum integrated accurately for 15 protons, the 13C NMR
spectrum displayed signals for all the carbon nuclei in the
expected product. This was further confirmed by the mass
spectrum that showed molecular ion peak at m/z of 301.10
[(8), M+]. No product was formed when the reaction was
run in the absence of the ligand, XPhos, even when reaction
was conducted over a longer period (25 h). Similarly, the
use of PPh3 in place of XPhos gave no conversion after
8 h and a little amount of conversion (less than 10%) after
25h, further confirming that the ligand played a crucial role
in the cross-coupling reaction. Apart from the bulkiness that
has been proven to aid in generation of monoligated com-
plex ion, L1Pd that was believed to undergo oxidative reac-
tion more readily than [PdL2] complex [51–53], the strong
σ electron donating character of XPhos appears to contrib-
ute to the ease with which 2-chloro-10H-phenothiazine
was coupled to boronic acid. It was speculated that the elec-
tron richness of the ligand minimized the binding of the het-
eroatoms in the substrate to metal center thereby increasing
the rate of the reaction as well as yields of expected product.
Excess boronic acid was employed to compensate for the
part that might be converted to side products such as
homocoupled products as the catalyst is being reduced to
its active Pd(0). The use of Na2CO3 in place of K3PO4 gave
lower product yields (24%), while K2CO3 gave comparable
yields with K3PO4 under these conditions. Furthermore,
there was no significant difference in product yields when
DMF/H2O (2:1) and n-BuOH/H2O (2:1) were used in place
of CH3CN/H2O (2:1) under these conditions. Buchwald
applied CH3CN/H2O (1.5:1) per millimoles of halide to
achieve excellent yields of biaryls [16]. Moseley [54] ob-
served that acetonitrile, ethanol, and THF in combination
with water at 9:1, 4:1, and 1:1 ratios made little difference
in the Suzuki–Miyaura cross-coupling reaction of (hetero)
chloroaromatics with Pd(dbpf)Cl2 as preformed catalyst.
The reactions performed without solvent degassing did give
comparable yield of products under these conditions. Al-
though only Pd(OAc)2 was applied as palladium source in
RESULTS AND DISCUSSION
The synthesis of the desired derivatives of phenothia-
zines and phenoxazines begins with synthesizing the
pharmacologically relevant intermediates by employing
the traditional anhydrous base catalyzed coupling reaction
of 2,3-dichloro-1,4-naphthoquinone 5 with 2-aminothio-
phenol, 2-aminophenol, and 2-aminopyridinol (Scheme 1).
Inspired by Buchwald’s earlier work [16,48–50] on
application of dicyclohexylbiphenylphosphine-based catalytic
system (such as XPhos) as a generic catalyst in Suzuki–
Miyaura cross-coupling of (hetero)aryl substrates, the reac-
tion protocol for derivatization of chlorophenothiazines/
chlorophenoxazines was developed along the same line.
Pd(OAc)2 and XPhos (Pd/L = 1:2) was chosen as catalytic
Scheme 1. Synthesis of intermediates.
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Table 1
Suzuki–Miyaura cross-coupling of chlorophenothiazines and phenoxazines.a
Entry
1
Aryl chloride
Boronic acid
Product
Reaction time (h)
Isolated % yieldb
6
67
2
8
60
3
8
51
4
8
55
5
6
6
7
71
43
7
7
54
(Continued)
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E. A. Onoabedje, U. C. Okoro D. W. Knight, and A. Sarkar
Vol 000
Table 1
(Continued)
Entry
8
Aryl chloride
Boronic acid
Product
Reaction time (h)
Isolated % yieldb
8
44
aReaction conditions: chlorophenothiazine/chlorophenoxazine (1 equiv.), boronic acid (1.2 .), K3PO4 (3 mM), CH3CN–H2O (2:1) (3 mL), Pd(OAc)2
(4 mol%), XPhos (7 mol%).
bIsolated yield after purification by flash column chromatography.
this reaction, it is possible that other common palladium salts
such as PdCl2 and Pd2(dba)3 in conjunction with XPhos
would effect similar transformation.
reaction optimization, the procedure was applied in cou-
pling other substrates to styrylboronic and phenylboronic
acids, running the reaction for a maximum of 8h. Table 1
gives the yields of product formations. Moderate to high
yields were recorded for all reactions. The reaction of
2-chloro-10H-phenothiazine with styrylboronic and
phenylboronic acids respectively gave higher yields than
6-chloro-5H-benzo[a]phenothiazin-5-one 6, 6-chloro-5H-
benzo[a]phenoxazin-5-one 7, and 6-chloro-5H-naphtho
[2,1-b]pyrido[2,3-e][1,4]oxazin-5-one 8 tetra cyclic sub-
strates. It was presumed that the electron richness of the
tetracyclic substrates and the steric hindrance provided by
the ketonic groups that are ortho to the chloro substituents
contributed to lower their yields. The molecular structures
of the synthesized compounds were established on the basis
of NMR, UV and mass spectroscopic, and microanalysis
Encouraged by the results from cross-coupling of 2-
chloro-10H-phenothiazine and styryl boronic acid to afford
2-styryl-10H-phenothiazine, the amount of the catalyst and
ligand was doubled with a view to increasing the product
yield, and 67% yield of coupled product was indeed
obtained. Therefore, the catalyst-ligand load for the reac-
tion was fixed at 4 mol% Pd(OAc)2 and 7 mol% XPhos
and reaction scope expanded to include the cross-coupling
of 2-chloro-10H-phenothiazine with phenyl boronic acid to
obtained 2-phenyl-10H-phenothiazine in isolated yield of
71% at a conversion of over 90%. Again the spectroscopic
and elemental analysis data were in agreement with molec-
ular structure and formula, C18H13NS. Without further
Scheme 2. Mechanism for XPhos catalyzed Suzuki-Miyaura cross-coupling reactions of chlorophenothiazine/chlorophenoxazine.
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data and were in agreement with the assigned molecular
structures and formulas. The number of aromatic (and vi-
nylic for 9, 10, 11, and 12) protons was nicely accounted
for in the proton magnetic spectra of the compounds that
were found at 8.88–6.56ppm. The vinylic protons were
highly deshielded by the pi electrons of the fused conjugated
tetracyclic rings that their chemical shifts [55] shifted from
their normal absorption range of 4.6–5.9 and merged with
aromatic protons in such a way that they are not distinguish-
able. The deshielding effect of the vinylic protons were
much pronounced in compounds 10, 11, and 12 because of
additive deshielding effect generated by the carbonyl group
ortho to the styryl moieties in the compounds. The carbon
nuclei were similarly accurately represented in the carbon
nuclear magnetic spectra for all compounds with the car-
bonyl carbon signals found in a far distance low field from
the other sp2 hybridized carbon peaks. Although derivatives
9–12 were prepared as mixture of E and Z isomers, they were
named as (E)-2-styryl-10H-phenothiazine, (E)-6-styryl-
5H-benzo[a]phenothiazin-5-one, (E)-6-styryl-5H-benzo[a]
phenoxazin-5-one, and (E)-6-styryl-5H-naphtho[2,1-b]pyrido
[2,3-e][1,4]oxazin-5-one respectively as a result of greater sta-
bilities of the E alkenes over the Z alkenes. The more stable E
alkene gives the major product. The IR absorption maxima
for carbonyl functional groups in synthesized compounds
were supposed to be in the range of 1610–1640cmꢀ1 lower
than the carbonyl frequency in 1,4-naphthoquinone
because of ionic resonance effect [56]. Furthermore, the
synthesized derivatives are highly colored with UV–visible
absorption maxima range of 268–814nm. The UV–visible
spectra data disclosed bathochromic shifts except
compound 9 as a result of increase in conjugation with
compounds 10 and 11 exhibiting the highest shifts. It was
speculated that the coplanarity of compounds 10–16
contributed to their red shifts as a result of extended pi con-
jugation. It had been reported that phenothiazine deriva-
tives with extended pi-conjugated substituents often
display intense luminescence upon UV–vis excitation with
Stokes shifts that might be due to solvent relaxation and, in
part, to geometry changes in excited state [21]. The favor-
able electronic properties of phenothiazine have led to their
applications as electrophore probes in supramolecular as-
semblies for photoinduced electron transfer and sensor
studies and as electron-donor components in material scien-
tific investigations such as electrically conducting charge-
transfer composites, polymers, Do–Acc arrangements, and
also as chromophores in dye-sensitized photovoltaic cells
[22]. Besides, the mass spectra data were in agreement with
molecular structures and formulas of the synthesized
derivatives. The mass spectra data were in agreement with
molecular structures and formulas of the synthesized
derivatives by furnishing their molecular ion peaks except
for compound 13 that gave no meaningful data. However,
results from elemental analysis of compound 13 were con-
sistent with its molecular formula and assigned structure.
By using 2-chloro-10H-phenothiazine electrophilic
substrate, we present a general mechanism for Suzuki–
Miyaura cross-coupling of chlorophenothiazine/chlorophe-
noxazine (Scheme 2).
CONCLUSION
The catalyst system generated from palladium acetate
and XPhos converted highly electron-rich and heterocyclic
chlorophenothiazines and chlorophenoxazines in moderate
to high yields to afford highly colored derivatives at rela-
tively mild reaction temperatures. The reaction conditions
tolerated both carbonyl functional groups and unprotected
N–H moiety in substrates. Further research is in progress
to optimize the reaction conditions and develop catalytic
system to explore related cross-coupling protocols to diver-
sify target molecular motifs.
EXPERIMENTAL
General information. Commercially available starting
materials and reagents were purchased from Aldrich Chemical
Company (UK) and were used without further
purification. Unless otherwise stated, all compounds were
synthesized and characterized in the School of Chemistry,
Organic Chemistry Laboratory, Cardiff University, Wales,
UK. Melting points were determined with a Fisher-Johns
apparatus and are uncorrected. 1H and 13C NMR data
were recorded with Brucker DPX 400 and 600MHz
spectrophotometer (UK) relative to TMS as internal
standard. All and chemical shifts reported in parts per
million (δ), and coupling constants (J) are reported in hertz.
Multiplicity is indicated using the following abbreviations:
br for broad, s for singlet, d for doublet, t for triplet, dd for
doublet of doublets, and m for multiplet. The mass spectral
data were obtained on a Varian 1200 Quadruple Mass and
Micromass Quadro II spectrometers (UK). Elemental
analysis was carried out with ThermoQuest FLASH series
(CHNS) elemental analyzer (UK). UV–visible spectra were
recorded on Cecil 7500 Aquarius 7000 series spectrometer
at Chemistry Advance Laboratory, Sheda Science and
Technology Complex Abuja, Nigeria, using matched 1cm
quartz cells and methanol as solvent. The absorption
maxima are recorded in nanometer (nm), and figures in
parenthesis are log of ε.
Synthesis of intermediates. 6-Chloro-5H-benzo[a]phenothiazin-
5-one, 6.
To a suspension of 2-aminothiophenol (2.5g,
20mM) in (50 mL) chloroform was added Na2CO3 (2.12g,
20mM), the mixture heated to boiling temperature before
adding 2,3-dichloro-1,4-napthoquinone (4.54 g, 20 mM), and
entire mixture refluxed for 3 h while stirring with magnetic
bar. The reaction mixture was cooled to room temperature,
and solvent was distilled off in a vacuum. Water (25 mL)
was added to the dark solid, stirred, and filtered to remove
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Vol 000
inorganic salts and air-dried. The solid was recrystallized from
benzene acetone after treatment with activated charcoals to
obtain reddish-brown shiny solid. Yield = 5.01 g (84%),
melting point: 220–222°C. δH (400 MHz CDCl3): 8.87–8.84
(1H, m); 8.33–8.31 (1H, m); 7.97–7.94 (1H, m), 7.74–7.72
(2H, m); 7.54–7.42 (3H, m). δc (600MHz CDCl3): 173.85
(carbonyl carbon), 143.80, 138.41, 135.20, 134.10, 133.29,
132.00, 131.62, 130.21, 128.34, 126.53, 125.97, 125.33,
125.18, 123.55. UV–visible λmax (MeOH): 381.5(7.06); 4.79
(7.21); 747.5 (6.97). IR (νmax cmꢀ1): 1640, 1593, 1578, 1510,
1290, 1155, 1090, 905, 855, 828, 777, 721, 681, 644. Anal.
Calcd. for C16H8ClNOS: C, 64.54; H, 2.71; Cl, 11.91; N, 4.70;
S, 10.77. Found: C, 64.59; H, 2.77; Cl, 11.71; N, 4.49; S, 10.89.
6-Chloro-5H-benzo[a]phenoxazin-5-one, 7. A mixture of
2-aminophenol (2.18 g, 20 mM) and KOH (2.24 g, 20mM)
was stirred at room temperature for ½ h in methanol
(100 mL) followed by addition of 2,3-dichloro-1,4-
napthoquinone (4.54 g, 20 mM), and the entire reaction
mixture stirred at room temperature for 6 h. The solvent
was distilled off in a vacuum, water (50 mL) added to the
yellowish-brown solid, stirred, and filtered, and solid
further wash with 5% HCl (25 mL) and air-dried. The
crude product was recrystallized from benzene toluene
after treatment with activated charcoal to give yellow-
orange-colored solid. Yield = 4.85g (86%), melting
point: 205–207°C. δH (400 MHz CDCl): 8.68–8.66 (1H,
m); 8.31–8.29 (1H, m); 7.81–7.79 (1H, dd, J = 7.80);
7.76–7.68 (2H, m); 7.49–7.46 (1H, m); 7.41–7.33 (2H,
m). δc (600 MHz CDCl3): 177.46 (carbonyl carbon), 146
.89, 146.15, 143.80, 132.63, 132.41, 132.09, 131.85,
131.44, 130.27, 129.93, 126.63, 125.85, 124.94, 116.19.
UV–visible λmax (MeOH): 354.5 (7.88); 440 (7.54); 747
(7.01). IR (νmax cmꢀ1): 1640, 1570, 1330, 1310, 1280,
1250, 1150, 1100, 1010, 920, 840, 780, 760, 690. Anal.
Calcd for C16H8ClNO2: C, 68.22; H, 2.86; Cl, 12.58; N,
4.97. Found: C, 68.31; H, 3.01; Cl, 12.75; N, 5.10.
68.22; H, 2.86; Cl, 12.58; N, 4.97. Found: C, 68.39; H,
3.02; Cl, 12.77; N, 5.10.
The general procedure for Suzuki cross-coupling reactions.
To an oven dried 10-mL round-bottom flask containing
2 mL of CH3CN and 1 mL of water was charged with RX
(1 mM), RB(OH)2 (1.2 mM), and K3PO4 (588mg, 3mM),
and the entire reaction mixture degassed for ½ h by gentle
bubbling of nitrogen gas through the reaction vessel
while stirring gently with magnetic bar. The reaction
temperature was gradually increased to 40°C before Pd
(OAc)2 (8.92mg, 4mol%), XPhos (32.5mg, 7mol%) were
added, and reaction vessel was immediately corked with
rubber septum. The reaction left under the temperature of
30°C for 30 min before raising to 80°C. After 5–8h, the
reaction was cooled to room temperature, and solvent
evaporated in a vacuum. This was followed by addition of
5mL of water, and crude product extracted with
dichloromethane (DCM) (10mL×4). The combined
organic extracts were dried with MgSO4, and crude product
was purified by flash column chromatography on silica gel.
(E)-2-Styryl-10H-phenothiazine, 9. The general procedure
was used to convert styryl boronic acid and 2-chloro-
10H-phenothiazine to the title product in 6h. Purification
by flash chromatography (5% EtOAc/95% pet ether as
the eluent) gave the analytically pure product as yellow
solid, mp 168–169°C; % yields=202mg (67%). δH
(400MHz, CDCl3): 7.85(1H, s, br, N–H proton); 7.43–
7.37 (1H, m); 7.23–7.20 (1H, m); 7.13–7.11 (1H, m);
6.88–6.86 (1H, m); 6.90–6.76 (3H, m); 6.71–6.66 (3H, m),
6.61–6.56 (3H, m). δc (600MHz, CDCl3: 144.67, 142.38,
138.40, 133.69, 133.40, 130.24, 129.52, 129.31, 128.46,
128.39, 128.13, 127.32, 127.23, 123.38, 122.39, 118.03,
117.34, 115.69, 115.63, 115.03, 114.98. UV–visible λmax
(MeOH): 644.5 (6.87); 746 (7.03). MS (AP), m/z (%
relative intensity): 59.05(17), 80.05(12), 100.07(100),
117.09(72), 118.10(6), 167.08(2), 198.05(2), 199.05(18),
200.06(4), 233.01(28), 234.02(16), 235.01(12), 236.01(5),
275.04(20), 301.10[(8),M+], 302.11 [(20),M++1]. Anal.
Calcd. for C20H15NS: C, 79.70; H, 5.02; N, 4.65; S, 10.64.
Found: C, 79.51; H, 5.17; N, 4.70; S, 10.58.
6-Chloro-5H-naphtho[2,1-b]pyrido[2,3-e][1,4]oxazin-5-one, 8.
By method similar to preparation of compound 7, 6-
chloro-5H-naphtho[2,1-b]pyrido[2,3-e][1,4]oxazin-5-one,
8 was prepared from 2-aminopyridin-3-ol (2.20 g, 20 mM),
2,3-dichloro-1,4-napthoquinone (4.54, 20 mM), KOH
(2.24 g, 20 mM), and methanol (100 mL) as yellow-
orange solid and recrystallized from acetone after
treatment with activated carbon. Yield=4.47g (81%),
melting point: 207–208°C. δH (400MHz CDCl3): 8.84–
8.82 (1H, m); 8.62–8.61 (1H, dd, J=8.61); 8.32–8.30
(1H, m); 7.79–7.76 (3H, m), 7.45–7.43 (1H, dd, J= 7.45).
δc (600MHz CDCl3): 177.27 (carbonyl carbon), 150.23,
147.27, 146.09, 144.37, 140.68, 133.11, 132.93, 131.37,
129.83, 126.82, 126.21, 125.95, 124.59, 115.90. UV–
visible λmax (MeOH): 350.5 (7.38); 441.0 (7.47); 746
(7.03). IR (νmax cmꢀ1): 1650, 1565, 1560, 1555, 1420,
1330, 1900, 1270, 1230, 1120, 1100, 1030, 920, 870,
810, 775, 710, 690. Anal. Calcd. for C16H8ClNO2: C,
(E)-6-Styryl-5H-benzo[a]phenothiazin-5-one, 10. The general
procedure was employed to convert styrylboronic acid and
6-chlorobenzo-5H-phenothia-5-one to the title product in
8h. Purification by flash column chromatography with
10% EtOAc/90% pet ether as eluent gave analytically pure
product as dark purple solid, mp 181–183°C. Yield=
181mg (60%). δH (400MHz, CDCl3): 8.80–8.78 (1H, m);
8.28–8.26 (1H, m); 7.88–7.84 (2H, m); 7.69–7.65 (2H, m),
7.57–7.55 (2H, dd, J= 7.56); 7.43–7.39 (2H, m); 7.36–7.32
(3H, m), 7.27–7.24 (1H, t, J= 7.25); 7.07–7.03(1H, d,
J=7.05). δc (600MHz, CDCl3): 179.30 (carbonyl carbon,
C¼O), 145.28, 138.79, 138.44, 137.72, 134.25, 132.81,
132.52, 131.62, 131.22, 129.58, 128.75, 128.75, 128.47,
127.95, 127.07, 126.29, 125.46, 124.94, 123.43, 120.57.
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via Suzuki-Miyaura Cross-Coupling Reactions
UV–visible λmax (MeOH): 267.5 (8.12); 286.0 (8.05); 330
(7.89); 495.5(7.88); 814 (6.89). MS (AP), m/z (% relative
intensity): 124.07(45), 166.12(2), 231.11(2), 275.07(5),
348.09(7), 349.09 [(100), M+], 350 [(10), M+ +1]. Anal.
Calcd. for C24H15NOS: C, 78.88; H, 4.14; N, 3.83; S,
(2H, m). δc (600MHz, CDCl3): 143.72, 143.13, 141.39,
141.22, 129.68, 128.36, 128.27, 127.54, 127.29, 127.21,
122.97, 121.45, 118.27, 117.75, 115.51, 113.79. UV–
visible λmax (MeOH): 504.5(7.21); 324.5(8.15). Anal. Calcd.
for C18H13NS: C, 78.51; H, 4.76; N, 5.09; S, 11.64. Found:
8.77. Found: C, 78.91; H, 4.11; N, 4.02; S, 8.82.
(E)-6-Styryl-5H-benzo[a]phenoxazin-5-one, 11. General
C, 78.38; H, 4.88; N, 5.20; S, 11.52.
6-Phenyl-5H-benzo[a]phenothiazin-5-one, 14. The general
procedure was employed in conversion of phenylboronic
acid and 6-chloro-5H-benzo[a]phenothiazin-5-one to provide
the title product in 7 h. Purification by flash chromatography
(10% EtOAc/90% pet ether eluent) gave analytical pure
product as reddish solid, mp: dec above 180°C.
Yield=146 mg (43%). δH (400MHz, CDCl3): 8.85 (1H, d,
J=8.87); 8.30–8.27 (1H, dd, 8.28), 7.88–7.86 (1H, d,
J=7.87); 7.75–7.62 (3H, m); 7.51–7.36 (4H, m); 7.29–7.22
(3H, m). δc (600MHz, CDCl3): 178. 66 (carbonyl carbon,
C¼O), 144.80, 138 .32, 135.87, 134.62, 134.56, 132.85,
132 .31, 131. 92, 131.59, 131 .31, 129. 75, 129.50, 129.27,
129. 21, 128.76, 127.65, 126.12, 125.54, 124.84, 123.83,
115.27. UV–visible λmax (MeOH): 368.5 (7.46); 482.0
(7.45); 748.5 (7.07). MS (AP), m/z (% relative intensity):
74.06(1), 90.01(7), 92.10(4), 116.07(2), 252.05(1), 298.01(1),
338.35(1), 340.08[(100), M+ ꢀ1], 341.08[(29), M+ ꢀ2]. Anal.
Calcd. for C22H13NOS: C, 77.85; H, 3.86; N, 4.13; S, 9.45.
protocol was applied in the conversion of styrylboronic
acid and 6-chlorobenzo-5H-phenoxazin-5-one to the title
product in 8 h. Analytical pure product was obtained by
flash column chromatography using 10% EtOAc/ 90% pet
ether eluent as dark purple solid, mp: dec. above 185–
187°C. Yields = 179 mg (51%). δH (400 MHz, CDCl3):
8.60–8.58 (1H, m); 8.24–8.22 (1H, m); 8.04–8.00 (1H, d,
J=8.02); 7.74–7.63 (3H, m); 7.56–7.48 (3H, m); 7.44–
7.38(3H, m); 7.34–7.22(3H, m). δc (600MHz, CDCl3):
182.88 (carbonyl carbon, C¼O), 147.13, 146.62, 144.21,
138.45, 136.34, 133.12, 131.99, 131.72, 131.19, 130.97,
129.66, 128.10, 126.96, 126.37, 125.42, 124.47, 117.73,
115.79, 114.98. UV–visible λmax (MeOH): 287.5(7.81);
313.0 (8.01); 491.0 (7.43); 643.5(7.01); 737 (6.98); 809
(7.10). MS (AP), m/z (% relative intensity): 74.06(3),
90.01(9), 92.01(5), 116.06(5), 322.12(1), 343.90(4),
350.11[(100), M+ꢀ1], 351.11[(30), M+ꢀ2]. Anal. Calcd.
for C24H15NO2: C, 82.51; H, 4.33; N, 4.01. Found: C,
Found: C, 78.02; H, 4.01; N, 4.24; S, 9.56.
6-Phenyl-5H-benzo[a]phenoxazin-5-one, 15. The general
82.21; H, 4.53; N, 4.21.
(E)-6-Styryl-5H-naphtho[2,1-b]pyrido[2,3-e][1,4]oxazin-5-
one, 12. General protocol was applied in the conversion
procedure was used to convert phenylboronic acid and 6-
chloro-5H-benzo[a]phenoxazin-5-one to provide the title
product in 7h. Purification by flash column chromatography
(10% EtOAc/ 90% pet ether eluent) supplied the analytical
pure product as orange solid, mp: dec above 219°C.
Yields=174mg (54%). δH (400MHz, CDCl3): 8.69–8.67
(1H, d, J=8.68); 8.28–8.27 (1H, d, J=8.27); 7.74–7.67 (3H,
dd, J=7.71); 7.45–7.43 (4H, d, J=7.44); 7.35–7.33 (2H, d,
J= 7.37); 7.08–7.06 (1H, d, J=7.07). δc (600MHz, CDCl3):
182.37 (carbonyl carbon, C¼O), 147.39, 146.83, 144.11,
132.84, 132.03, 131.98, 131.83, 131.24, 131.04, 130.91,
130.68, 129.58, 128.07, 127.97, 126.49, 125.14, 124.51,
119.38, 116.01. UV–visible λmax (MeOH): 309.0 (8.87);
445.0 (8.96); 749 (6.60). MS (AP), m/z (% relative intensity):
74.06(2), 90.01(3), 115.09(3), 282.05(3), 324.12[(100), M+
ꢀ1], 325.13 [(25), M+ ꢀ2]. Anal. Calcd. for C22H13NO2: C,
of styrylboronic acid and 6-chlorobenzo-5H-naphtho[2,1-
b]pyrido[2,3-e]oxazin-5-one to the title product in 8h.
Purification by flash column chromatography (40% EtOAc/
60% pet ether eluent) gave the analytical pure product as
dark purple solid, mp: dec above 170°C. Yields=228mg
(65%). δH (400MHz, CDCl3): 8.75–8.73 (1H, dd, J=8.74);
8.53–8.51 (1H, dd, J= 8.52); 8.25–8.22 (1H, dd, J=8.24);
8.05–8.01 (1H, d, J=8.03); 7.71–7.65(3H, m); 7.55–7.53
(2H, d, J=7.54); 7.44–7.40 (1H, d, J=7.42); 7.37–7.30
(3H, m); 7.26–7.24(1H, m). δc (600MHz, CDCl3): 182.85
(carbonyl carbon, C¼O), 151.41, 146.71, 145.58, 145.03,
138.07, 137.73, 132.72, 132.49, 131.93, 128.75, 128.50,
127.07, 126.52, 125.56, 125.47, 124.05, 117.25. UV–visible
λmax (MeOH): 306.0 (8.99); 450.0 (7.65); 749.5 (6.87). MS
(AP), m/z (% relative intensity): 75.04(3), 90.01(36), 92.01(12),
116.07(6), 126.03(1), 279.09(1), 338.34(3), 351.11[(100), M+
ꢀ1], 352.11[(25), M+ ꢀ2]. Anal. Calcd. for C23H14N2O2: C,
81.72; H, 4.05; N, 4.33. Found: C, 81.91; H, 4.16; N, 4.21.
6-Phenyl-5H-naptho[2,1-b]pyrido[2,3-e][1,4]oxazin-5-one, 16.
The general procedure was used to convert phenylboronic
acid and 6-chloro-5H- naphtho[2,1-b]pyrido[2,3-e][1,4]
oxazin-5-one to the title product in 8h. Analytical pure
product was obtain by flash column chromatography (40%
EtOAc/60% pet ether eluent) as red solid, mp: dec. above
238°C. Yield =143mg (44%). δH (400MHz, CDCl3):
8.88–8.85 (1H, m); 8.53–8.51 (1H, dd, J =8.52); 8.31–
8.29 (1H, m); 7.78–7.75 (2H, m); 7.47–7.44 (5H, m);
7.40–7.37 (1H, m), 7.32–7.29 (1H, dd, J=7.31). δc
(600MHz, CDCl3): 182.41 (carbonyl carbon, C¼O),
151.75, 146.43, 145.95, 144.64, 140.91, 135.60, 132.94,
78.84; H, 4.03; N, 8.00. Found: C, 79.02; H, 4.15; N, 8.14.
2-Phenyl-10H-phenothiazine, 13. General protocol was
applied in the conversion of phenylboronic acid and 2-
chloro-10H-phenothiazine to obtain the title product in 6h.
Analytical pure product was obtained as yellow solid by
flash column chromatography (5% EtOAc/95% pet ether
eluent), mp: 146–147°C; % yields=195mg (71%). δH
(400MHz, CDCl3): 7.85 (1H, br, s, N–H proton), 7.44–7.42
(2H, d, J=7.43), 7.31–7.27 (2H, m); 7.22–7.18 (1H, m);
6.96–6.94 (1H, dd, J=6.95); 6.89–6.81 (4H, m); 6.68–6.60
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

E. A. Onoabedje, U. C. Okoro D. W. Knight, and A. Sarkar
Vol 000
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128.33, 128.09, 127.56, 127.27, 126.65, 125.77, 125.57,
124.44, 120.63, 115.45. UV–visible λmax (MeOH): 266.0
(8.96); 275.5 (8.83), 360.0 (8.63); 446.0 (8.15); 753.0
(6.55). MS(EI), m/z (% relative intensity): 65.0315(1),
83.9524(65), 104.0420(1), 162.0445(5), 189.0697(3),
214.0643(5), 240.0855(5), 266.0854(8), 295.0894(20),
312.1321(10), 323[(100), M+ +1]. Anal. Calcd. for
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Acknowledgments. We thank Petroleum Technology Development
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Journal of Heterocyclic Chemistry
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