Rapid Access to New Angular Phenothiazine and Phenoxazine Dyes

Article abstract of DOI:10.1002/jhet.2569

The synthesis of some new thiophenyl-derivatized and furanyl-derivatized phenothiazine and phenoxazine dyestuffs is described. This was achieved by two methods after the synthesis of 6-chloro-5H-benzo[a]phenothiazin-5-one, 6-chloro-5H-benzo[a]phenoxazin-5-one, and 6-chloro-5H-naphtho[2,1-b]pyrido[2,3-e][1,4]oxazin-5-one intermediates via anhydrous base condensation reaction of 2,3-dichloro-1,4-naphthoquinone with 2-aminothiophenol, 2-aminophenol, and 2-aminopyridinol, respectively. The first method involved treatment of tributyl(thien-2-yl) or tributyl(furan-2-yl) stannane with chlorophenothiazine/chlorophenoxazine under mild basic chemical formula (CsF) and 1,4-dioxane or toluene solvent at 80°C to supply dazzling yellow solid in high yields. In the second method, the catalytic system was pre-activated in acetonitrile, followed by addition of coupling partners and K₃PO₄to obtain high melting and variety of highly colored products in moderate to high yields. The reaction conditions were compatible with unprotected N–H and carbonyl functional groups. The intense colors of these dyes and their ease of re-oxidation of Na₂S₂O₄-reduced derivatives make them suitable as vat dyes. Also, they were found to be good colorants for textiles, papers, paint, ink, soap, polish, candle, and plastic materials.

Full text of DOI:10.1002/jhet.2569

Month 2015
Rapid Access to New Angular Phenothiazine and Phenoxazine Dyes
a
a
b
*
Efeturi A. Onoabedje, Uchechukwu C. Okoro, and David W. Knight
aDepartment of Pure and Industrial Chemistry, University of Nigeria, Nsukka, Nigeria
bSchool of Chemistry, Department of Organic Chemistry, Cardiff University, Wales, UK
*
E-mail: efeturi.onoabedje@unn.edu.ng
Additional Supporting Information may be found in the online version of this article.
Received September 4, 2015
DOI 10.1002/jhet.2569
Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com).
The synthesis of some new thiophenyl-derivatized and furanyl-derivatized phenothiazine and
phenoxazine dyestuffs is described. This was achieved by two methods after the synthesis of 6-chloro-5H-
benzo[a]phenothiazin-5-one, 6-chloro-5H-benzo[a]phenoxazin-5-one, and 6-chloro-5H-naphtho[2,1-b]
pyrido[2,3-e][1,4]oxazin-5-one intermediates via anhydrous base condensation reaction of 2,3-dichloro-
1,4-naphthoquinone with 2-aminothiophenol, 2-aminophenol, and 2-aminopyridinol, respectively. The first
method involved treatment of tributyl(thien-2-yl) or tributyl(furan-2-yl) stannane with chlorophe
nothiazine/chlorophenoxazine under mild basic chemical formula (CsF) and 1,4-dioxane or toluene solvent
at 80°C to supply dazzling yellow solid in high yields. In the second method, the catalytic system was pre-
activated in acetonitrile, followed by addition of coupling partners and K3PO4 to obtain high melting and
variety of highly colored products in moderate to high yields. The reaction conditions were compatible with
unprotected N–H and carbonyl functional groups. The intense colors of these dyes and their ease of re-
oxidation of Na2S2O4-reduced derivatives make them suitable as vat dyes. Also, they were found to be good
colorants for textiles, papers, paint, ink, soap, polish, candle, and plastic materials.
J. Heterocyclic Chem., 00, 00 (2015).
INTRODUCTION
phenothiazine [1]. On the other hand, Meldola [22] had
synthesized large numbers of phenoxazine derived dyes
in the last quarter of the last century. Notable among them
was Meldola’s blue 5 which is a textile, paper and paint
colorant.
The plethora industrial applications of phenothiazine
and phenoxazine and their derivatives stimulated our inter-
est in synthesizing new derivatives of the parent rings 1
and 2 that may be useful as dyestuffs [1,2].
Compounds 1 and 2 were first prepared by Bernthsen in
1883 and 1887 by thionation of diphenylamine and thermal
condensation of o-aminophenol with catechol (2-
hydroxyphenol), respectively [3,4].
Besides their well-known physiological activity profile,
[23,24] because of their reversible oxidative reactions,
which give rise to characteristic, deep colored radical cat-
ion absorptions, more recently, phenothiazine derivatives
have become attractive spectroscopic probes in molecular
arrangements for photoinduced electron transfer studies
and as scientific motif materials [25,26]. Also, recent re-
ports revealed that phenoxazine derivatives are widely ap-
plied as organic light emitting diodes [27,28].
Previously, derivatizations of these compounds were
achieved by employing classical reactions, which are gen-
erally harsh and unamenable to sensitive functional groups.
Burgess [29] noted in his review of benzophenoxazine-
based dyes for labeling biomolecules that most of the syn-
thetic protocols involved elevated temperature and were
Originally, these compounds and their derivatives were
mainly applied as dyes and pigments [5] in industries, but
with time, they found wider applications as antioxidant in lu-
bricants and fuel [6–9], polymerization stabilizers [10–12],
pesticides/insecticides [13–15], biological stains or label-
ings [16–19], acid–base indicators [20], and as drugs
[21]. Some phenothiazine derivatives, especially Lauth’s
violet 3 and Methylene blue 4, were known to be commer-
cial dyestuffs even before the first synthesis of the parent
© 2015 HeteroCorporation

E. A. Onoabedje, U.C. Okoro, and D. W. Knight
Vol 000
based on procedure that are now over a century old and no
contemporary synthetic methods were employed. How-
ever, in the recent time, a considerable variety of
phenothiazine derivatives had been synthesized from
iodo-substituted and/or bromo-substituted phenothiazine
precursor via metal catalyzed cross-coupling reactions
[30–34]. Grosu et al. [32] reported multistep synthesis of
3,7,10-substituted phenothiazine derivatives in which one
of the steps involved Pd-catalyzed Suzuki–Miyaura cross-
coupling of bromophenothiazines. Kramer [31] employed
the Suzuki–Miyaura cross-coupling of bromophenothiazine
in the synthesis of (hetero) aryl bridged and directly linked
active phenothiazinyl dyads and triads.
In a similar reaction, bromophenothiazines were used as
starting materials in the synthesis of phenothiazinyl acid
derivatives via halogen–metal exchange and electrophilic
borylation route [34] and synthesis of functionalized
oligophenothiazines via one-pot bromine–lithium exchange-
borylation-Suzuki coupling [33]. Muller [35,36] and his
co-workers reported the synthesis of luminescent, redox-
active diphenothiazine dumb-bells expanded by conjugated
arenes and heteroarenes and 3-acceptor-substituted and
3,7-bisacceptor-substituted phenothiazine via Pd-catalyzed
cross-coupling of bromophenothiazines. In our previous pa-
pers, we have reported the synthesis of new nonlinear polycy-
clic aza phenothiazine dyestuffs [37,38]. We have also
recently reported the functionalization of phenothiazine and
phenoxazine ring systems via Pd-catalyzed Suzuki–Miyaura
cross-coupling reaction [39]. In continuation of our avid inter-
est in developing new dyestuffs, we now report a convenient
synthesis of new phenothiazine-derivatized and phenoxazine-
derivatized dyestuffs employing Pd-catalyzed Stille cross-
coupling protocols.
anhydrous base-catalyzed reaction of 2,3-dichloro-1,4-
naphthoquinone 8 with 2-aminothiophenol, 2-aminophenol,
and 2-aminopyridin-3-ol 7 (Scheme 1).
Influenced particularly by the work of Buchwald and co-
workers [42] who applied pre-milled palladium acetate and
XPhos catalytic system in successful cross-coupling of ste-
rically and electronically diverse aryl chlorides with organo
tin reagents, their protocol was adapted in this work. How-
ever, unlike Buchwald reaction protocol, the catalytic sys-
tem was not pre-milled. Test experiments were conducted
by reacting 2-chloro-10H-phenothiazine (1 mmol) with
tributyl-(2-thienyl)stannane (1.2 mmol) in order to obtain
2-(thiophen-2-yl)-10H-phenothiazine 16 under a variety
of conditions. Applying catalytic loadings of 4 mol% Pd
(OAc)2 and 7 mol% XPhos four experiments were set up
using 3 mmol of Tetrabutylammoniumfluoride (TBAF),
CsF, K3PO4, and K2CO3 respectively and 3mL of 1,4-
dioxane under N2 atmosphere at the temperature of 80°C
and reaction progress monitored with thin-layer chroma-
tography. Full conversion of starting materials was ob-
served within 4h with CsF, about 50% conversion with
K3PO4 and K2CO3 and none were recorded for TBAF even
when reaction time was extended to 8 h. Yellow solid was
isolated in 80% yield after reaction work-up and purifica-
tion by flash column chromatography on silica gel using
20% dichloromethane–80% petroleum ether solvents.
Spectroscopic and elemental analysis data correspond to
molecular structure of compound and formula,
C16H11NS2. The proton nuclear magnetic spectra integra-
tion traces were consistent with 11 protons and in harmony
with carbon signals supplied by carbon-13 nuclear mag-
netic resonance spectroscopy. This was further validated
by molecular ion peak with m/z 281.0339 [(100), M+],
found in mass spectrum. There was no significant differ-
ence in product yield when toluene and tertiary butanol sol-
vents were used with CsF instead of 1,4-dioxane. The
reaction scope was also expanded by coupling 2-chloro-
10H-phenothiazine (1 mmol) with tributylfuranylstannane
13 to obtain 77% isolated yield of 2-(2-furanyl)-10H-phe-
nothiazine 20. Compound 20 is a shiny yellow powdery
solid. It was believed the use of CsF enhanced the reaction
rate as well the corresponding yields of the product be-
cause recent findings have associated increased reactivity
RESULTS AND DISCUSSION
Besides 2-chloro-10H-phenothiazine 6 that is commer-
cially available for the palladium(0)/XPhos-mediated Stille
cross-coupling, 6-chloro-5H-benzo[a]phenothiazin-5-one
9, 6-chloro-5H-benzo[a]phenoxazin-5-one 10, and 6-
chloro-5H-naphtho[2,1-b]pyrido[2,3-e][1,4]oxazin-5-one
11 were synthesized by employing the traditional [40,41]
Scheme 1. Synthesis of reaction intermediates.
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in Stille reactions to fluoride additive [43]. This was attributed
to the formation of hypervalent fluorostannane anions 14,
which undergo labile transmetalation reactions (Scheme 2).
Buchwald practically recorded greatest enhancement
with CsF [42]. Encouraged by these procedural develop-
ments, we applied them as a general protocol for the cou-
pling of chlorophenothiazine and chlorophenoxazine
substrates with organotin, but the reaction failed with the
angular-fused chlorophenothiazines and chlorophe
noxazines (9–11), generating only trace conversions. Ini-
tially, the failure of the reaction protocol to couple nonlin-
ear chlorophenothiazine and chlorophenoxazine substrates
with organotin was attributed to the inability of the cata-
lytic system to activate the aryl halide toward oxidative ad-
dition, which is generally known to be a crucial stage in the
catalytic cycle. Hence, a modified protocol was sought. In
this procedure, the catalyst and ligand was charged in a
10mL round bottom (RB) flask and corked with rubber
septum followed by air evacuation and corresponding back
filling with N2 gas four times before addition of
predegassed solvent followed by warming to 50°C within
10min. The rubber septum was immediately removed from
flask to add ArCl and CsF and replaced again. This was
followed by injection of 1.2 mmol of organostannane, and
the reaction temperature was maintained under inert atmo-
sphere for 30min before increasing to 80°C. The isolated
products at the completion of the reaction gave over 70%
yields dehalogenated product instead of 6-thiophenyl or
6-furanyl substituted products. For example, the reaction
of 6-chloro-5H-benzo[a]phenothiazin-5-one
9
with
tributylthienylstannane 12 gave 5H-benzo[a]phenothiazin-
5-one 15 (Scheme 3). The proton nuclear resonance spec-
trum integrated accurately for nine aromatic protons with
the proton in position 6 of the compound 15 found unusu-
ally upfield at 6.75ppm probably due to the additive
shielding effects conferred on it by the ring current and the
carbonyl functional group.
The failure of the reaction to provide desired products
compelled us to search for an alternative protocol to couple
organostannanes to 6-chlorobenzo[a]phenothiazines and 6-
chlorobenzo[a]phenoxazines 9–11 (Scheme 3). Reasoning
C–Sn bond is more polar than C–B, we expected an en-
hanced transmetalation step for cross-coupling organos
tannanes over organoboranes. With this hypothesis, we
invoked earlier reaction protocol [39] employed in cross-
coupling of angular phenothiazine/phenoxazine chlorides
with organoboranes to afford moderate isolated yields of
derivatized products. The yield was further improved by first
preactivating the catalyst-ligand system by warming in aque-
ous acetonitrile to 50°C before adding K2CO3, ArCl, and
organostannane, and the reaction continued until satisfactory
consumption of starting materials was observed (Scheme 4).
Encouraged by the result of this tested procedure, it was
extended to the coupling of angular chloropheno
thiazine/chlorophenoxazines with organostannane, and
the results are presented in Table 1. The results show that
moderate to high yields of derivatized products were ob-
tained applying the developed procedure to five coupling
reactions. The coupling of 2-chloro-10H-phenothiazine
substrate with organostannanes gave the highest yields of
products in shorter time and this may be attributed to
higher electrophilicity as well as freer access to the reaction
site of the substrate. The proton nuclear magnetic reso-
nance spectroscopic chemical shifts for the aromatic
protons of products 16–22 appeared in the range of 8.88–
6.54 ppm with the integration traces in agreement with
Scheme 2. Formation and reaction of hypervalent fluoro-(2-thienyl)
stannane anion.
Scheme 3. Pd(0)/XPhos-catalyzed Stille cross-coupling under various conditions.
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E. A. Onoabedje, U.C. Okoro, and D. W. Knight
Vol 000
Scheme 4. Pd(0)/XPhos catalyzed Stille preactivated reaction.
Table 1
Stille cross-coupling of chlorophenothiazines and chlorophenoxazinesa.
Entry
1
Aryl chloride
Organotin
Product
Time (h)
4
Yieldb (%)
81
2
3
4
12
12
12
6
6
6
53
73
78
5
6
5
6
77
67
13
13
7
6
70
aReaction conditions: chlorophenothiazine/chlorophenoxazine (1.0 equiv), organotin (1.5 equiv.), K3PO4 (3 equiv), CH3CN (3 mL), Pd(OAc)2 (4 mol%),
and XPhos (7 mol%). Entries 1 and 5: CsF (3 equiv) was used instead of K3PO4.
bIsolated yield after purification by flash column chromatography.
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Scheme 5. Proposed mechanism for Pd(0)/XPhos catalyzed Stille cross-coupling reactions.
the number of protons in the respective compounds. These
results were nicely substantiated by carbon nuclear mag-
netic spectroscopic data, which furnished the number of
peaks corresponding to the number of carbons in each
compound in the range of 181.98–109.49 ppm. The car-
bonyl carbon of each compound were distinguishable from
the rest and were found in 178.47, 181.91, 181.02, and
180.98 ppm at higher frequency than other sp2 hybridized
carbons, indicating that the carbonyl groups were well
tolerated.
scientific investigations such as electrically conducting
charge-transfer composites, polymers, Do-Acc arrange-
ments, and also as chromophores in dye-sensitized photo-
voltaic cells [26]. Furthermore, derivatives 16–22 were
found to be good colorants for textiles, papers, paint, ink,
soap, polish, candle, and plastic and cosmetic products.
By using 6-chloro-5H-benzo[a]phenothiazine 9 electro-
philic substrate, we propose a general plausible mechanism
for the syntheses of derivatives 17–19, 21, and 22
(Scheme 5).
The prepared compounds were all colored and have
strong absorptions in the visible region of the electromag-
netic spectra (400–800nm). They also exhibit slight red
shifts due to their extended conjugations. Phenothiazine
derivatives with extended π-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 the excited state [25]. The
electronic properties of these compounds 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
The reduction of compounds 17–19, 21, and 22 to their
corresponding angular phenothiazinols/phenoxazinols was
accomplished by using sodium dithionite. For example,
17 easily loses its reddish color on refluxing in sodium
dithionite due to the formation of 6-(thiophen-2-yl)-12H-
benzo[a]phenothiazin-5-ol compound 23 (Scheme 6).
However, the reduced yellowish compound was too un-
stable to be isolated in their pure forms as they easily
reverted under atmospheric condition to the intensely
reddish colored oxidized iminoquinoid compound. This
property makes the synthesized derivatives applicable
as vat dyes.
Scheme 6. Reduction of thiophenylbenzophenothiazinone to thiophenylbenzophenothiazinol.
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E. A. Onoabedje, U.C. Okoro, and D. W. Knight
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CONCLUSION
130.21, 128.34, 126.53, 125.97, 125.33, 125.18, 123.55.
UV-Visible λmax (MeOH): 381.5 (4.06); 479 (3.21);
747.5 (3.97). IR (νmax, cmꢀ1): 1640, 1593, 1578, 1510,
1290, 1155, 1090, 905, 855, 828, 777, 721, 681, 644.
Found: C, 64.57; H, 2.74; N, 4.72; S, 10.79%. Molecular
formula C16H8ClNOS requires C, 64.54; H, 2.71; N,
New and highly colored phenothiazine and phenoxazine
dyes were prepared from Pd(0)/XPhos-catalyzed cross-
coupling of chlorophenothiazines/chlorophenoxazines
with organotins in moderate to high yields at relatively
mild temperature. These dyestuffs were found to be good
colorants for textiles, papers, paint, ink, soap, polish, can-
dle, plastic and cosmetic materials.
4.70; S, 10.77%.
6-Chloro-5H-benzo[a]phenoxazin-5-one (10). A mixture
of 2-aminophenol (2.18g, 20mmol) and KOH (2.24 g,
20mmol) was stirred at room temperature for 0.5h in
methanol (100mL) followed by addition of 2,3-dichloro-
1,4-naphthoquinone (4.54g, 20mmol), and the entire
reaction mixture was stirred at room temperature for 6h.
The solvent was distilled off in vacuum, and water
(50 mL) was added to the yellowish brown solid, stirred,
and filtered and solid further wash with 25mL of 5%
HCl 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%), mp 199–201°C (Lit.45 203°C). δH (400MHz,
CDCl3): 8.68–8.66 (1H, m); 8.31–8.29 (1H, m); 7.81–
7.79 (1H, dd, J= 7.80, 7.81); 7.76–7.68 (2H, m); 7.49–
7.46 (1H, m); 7.41–7.33 (2H, m). δc (150MHz CDCl3):
177.46 (C¼O), 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-Vis λmax (MeOH): 354.5 (3.88); 440
(3.54); 747 (4.01). IR (νmax, cmꢀ1): 1640, 1570, 1330,
1310, 1280, 1250, 1150, 1100, 1010, 920, 840, 780, 760,
690. (Found: C, 68.92; H, 2.77; N, 4.78. Molecular
formula C16H8ClNO2 requires C, 68.22; H, 2.86; N,
EXPERIMENTAL
General information.
All chemicals were purchased
from Aldrich Chemical Company, UK, and were used
without further purification. Otherwise stated, all
compounds were synthesized and characterized in the
School of Chemistry of Cardiff University, UK. Melting
points were determined with a Fischer-Johns apparatus.
1H and 13C-NMR data were recorded with Brucker DPX
400MHz spectrometers relative to tetramethylsilane as
internal standard. All chemical shifts are reported in ppm
(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 spectra data were obtained on a
Varian 1200 Quadruple Mass and Micromass Quadro II
spectrometers. Elemental analysis was carried out with
Thermo Quest Flash 1112 series (CHNS) Elemental
Analyzer. UV-Visible spectra were recorded on Cecil
7500 Aquarius 7000 Series Spectrometer at Chemistry
Advance Laboratory, Sheda Science and Technology
Complex (Shestco) Abuja, Nigeria, using matched 1cm
quartz cells and methanol as solvent. The absorption
maxima are recorded in nanometers (nm) and figures in
parenthesis are log ε.
Synthesis of angular phenothiazine and phenoxazine
intermediates. 6-Chloro-5H-benzo[a]phenothiazin-5-one (9).
To a suspension of 2-aminothiophenol (2.5 g, 20mmol) in
chloroform (50 mL) was added Na2CO3 (2.12 g, 20mmol)
and the mixture warmed to boiling before addition of 2,3-
dichloro-1,4-naphthoquinone (4.54 g, 20 mmol), and the
entire mixture refluxed for 3h while stirring with
magnetic bar. The reaction mixture was cooled to room
temperature, and solvent was distilled off in vacuum.
Water (25 mL) was added to the dark solid stirred and
filtered to remove inorganic salts and air-dried. The solid
was recrystallized from benzene-toluene after treatment
with activated charcoal to obtain reddish brown shiny
solid (5.01 g, 84%), mp 228–230°C (Lit.44 232°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 (150 MHz CDCl3): 173.85 (carbonyl carbon),
143.80, 138.41, 135.20, 134.10, 133.29, 132.00, 131.62,
4.97%).
6-Chloro-5H-naphtho[2,1-b]pyrido[2,3-e][1,4]oxazin-5-one
(11). By a similar method to the synthesis of 4, 6-chloro-
5H-naphtho[2,1-b]pyrido[2,3-e]oxazin-5-one was prepared
from 2-aminopyridin-3-ol (2.20g, 20mmol), 2,3-dichloro-
1,4-naphthoquinone (4.54g, 20mmol), and KOH (2.24g,
20mmol) in methanol (100mL) as a yellow-orange solid,
recrystallized from acetone after treatment with activated
carbon (yields 4.47g, 81%), mp 207–208°C. δH (400MHz
CDCl3): 8.84–8.82 (1H, m); 8.62–8.61 (1H, dd, J=8.61,
8.64); 8.32–8.30 (1H, m); 7.79–7.76 (3H, m), 7.45–7.43
(1H, d, J=7.45). δc (150MHz 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 (3.38); 441.0
(3.47); 746 (4.03). IR (νmax, cmꢀ1): 1650, 1565, 1560,
1555, 1420, 1330, 1900, 1270, 1230, 1120, 1100, 1030,
920, 870, 810, 775, 710, 690. (Found: C, 68.31; H, 2.89;
N, 5.01%. Molecular formula C16H8ClNO2 requires C,
68.22; H, 2.86; N, 4.97).
General procedures for Stille reactions: Method 1. To an
oven-dried 10mL RB flask was added Pd(OAc)2 (8.92mg,
4 mol%), XPhos (32.5mg, 7mol%), chlorophenothiazine
(234 mg, 1 mmol%), and CsF (459mg, 3 mmol), and the
vessel was covered with a rubber septum. The flask was
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Rapid Access to New Angular Phenothiazine and Phenoxazine Dyes
evacuated and backfilled with N2 thrice before injection of
degassed dioxane or toluene (3 mL) and, as temperature of
reaction mixture was gradually heated to 50°C tributyl-(2-
thienyl)stannane (1.2 mmol), was injected into the flask.
The temperature was maintained for 30 min before
increasing to 80°C. The reaction was terminated in 4h
and cooled to room temperature. Reaction mixture was
diluted with DCM (3 mL) and extracted from water
(5 mL) with 5 mL of DCM four times. The combined
organic extract was dried with MgSO4 and concentrated
in vacuum. The crude product was purified by flash
chromatography on silica gel using petroleum ether-
chromatography employing 10% EtOAc/90% pet. ether as
eluent gave analytically pure dark brown solid product,
yield 183mg (53%), mp >200°C (dec). NMR: δH
(400MHz, CDCl3): 8.88–8.85 (1H, m); 8.31–8.29 (1H,
m); 7.91–7.89 (1H, d, J=7.90); 7.76–7.67 (2H, m); 7.56–
7.54 (1H, dd, J=7.55, 7.51); 7.44–7.40 (1H, m); 7.37–
7.32 (1H, dd, J=7.28, 7.18); 7.18–7.17 (3H, m). δC
(150MHz, CDCl3): 178.47, 144.77, 138.41, 136.95,
134.61, 134.34, 132.17, 131.77, 131.38, 129.87, 129.04,
128.41, 127.88, 126.84, 125.65, 125.07, 124.88, 124.88,
123.67. HRMS (EI), m/z (% relative intensity): 83.9667
(100), 149.0583 (3), 207.0481 (3), 284.0637 (4), 316.0423
(7), 345.0280 [(30), M+]. UV-Visible λmax (MeOH): 369.0
(3.11); 484.5 (4.04); 743.5 (3.77). (Found: C, 69.61; H,
3.19; N, 4.01; S, 18.59%. Molecular formula C20H11NOS2
requires C, 69.54; H, 3.21; N, 4.05; S, 18.56.)
ethyl acetate.
General procedures for Stille reactions: Method 2. An
oven-dried 10mL RB flask was charged with Pd(OAc)2
(8.92mg, 4mol%) and XPhos (32.5mg, 7mol%) and
covered with rubber septum. The vessel was evacuated and
backfilled with N2 thrice before injecting CH3CN (2mL)
and H2O (1mL) (both solvents degassed for 30min), and
the reaction mixture warmed to 50°C within 10 min. Rubber
septum was quickly removed to charge with
chlorophenothiazine (1mmol) and K3PO4 (318mg,
1.5mmol) and replaced before injecting tributyl thienyl
\stannane or tributyl furanyl stannane (1.2 mmol). The
temperature was maintained for 30 min before increasing
to 80°C. The reaction was terminated in 5 h and diluted
with DCM (5 mL), and the crude product was extracted
from water (5 mL) four times with DCM. The combined
organic extract was dried with MgSO4 and concentrated
in vacuum. The crude product was purified by flash
chromatography on silica gel using petroleum ether-ethyl
6-(Thiophen-2-yl)-5H-benzo[a]phenoxazin-5-one
(18)
(Table 1, entry 3).
Method 2 was used to prepare the
title product from the cross-coupling of tributyl 2-thienyl
stannane with 6-chloro-5H-benzo[a]phenoxazin-5-one in
6 h. Purification by flash chromatography applying 10%
EtOAc/90% pet. ether as eluent provided the analytically
pure dark brown solid product, yield 240mg (73%), mp
203–204°C. NMR: δH (400MHz, CDCl3): 8.57–8.65
(1H, m); 8.33–8.31 (1H, m); 8.22–8.20 (1H, dd, J = 8.21,
8.21); 7.79–7.77 (1H, dd, J =7.74, 7.74); 7.72–7.68 (2H,
m); 7.52–7.50 (1H, dd, J =7.51–7.47); 7.47–7.39 (2H,
m); 7.34–7.30 (1H, m); 7.19–7.16 (1H, m). δc (150MHz,
CDCl3): 181.91 (C¼O), 146.85, 145.05, 143.85, 132.89,
132.09, 131.81, 131.78, 131.67, 131.35, 130.07, 129.60,
128.63, 126.62, 126.22, 125.55, 124.43, 115.85, 112.73.
UV-Visible λmax (MeOH): 364.5 (4.08); 493.0 (3.64);
750.0 (4.02). HRMS (EI), m/z (% relative intensity):
83.9533 (100), 142.5381 (8), 174.0802 (3), 240.0802 (3),
272.0522 (10), 301.0556 (12), 329.0512 [(93), M+].
(Found: C, 72.98; H, 3.40; N, 4.31%. Molecular formula
C20H11NO2S requires C, 72.93; H, 3.37; N, 4.25; S, 9.73.)
6-(Thiophen-2-yl)-5H-naphtho[2,1-b]pyrido[2,3-e][1,4]oxazin-
5-one (19) (Table 1, entry 4). Method 2 was used to cross-
couple tributyl 2-thienyl stannane with 6-chloro-5H-
naphtho[2,1-b]pyrido[2,3-e][1,4]oxazin-5-one to afford the
title product within 6h. Purification by flash
chromatography (45% EtOAc/ 55% pet. ether eluent) gave
the analytically pure dark brown solid product, yield
257mg (78%), mp >210°C (dec). NMR: δH (400MHz,
CDCl3): 8.76–8.74 (1H, m); 8.55–8.53 (1H, dd, J=8.54,
8.54); 8.26–8.24 (1H, m); 8.14–8.13 (1H, dd, J=8.14);
7.72–7.67 (2H, m); 7.51–7.49 (1H, dd, J= 7.50, 7.50);
7.38–7.35 (1H, dd, J= 7.37, 7.30); 7.13–7.11 (1H, dd,
J=7.12, 7.10). δc (600MHz, CDCl3): 181.95(C¼O),
151.08, 146.95, 144.74, 144.01, 140.63, 132.81, 132.60,
131.58, 131.21, 130.77, 130.27, 129.52, 126.76, 126.41,
125.73, 125.41, 124.12, 113.81. UV-Visible λmax
(MeOH): 370.0 (3.81); 506.0 (3.24); 745.0 (3.87). HRMS
(EI), m/z (% relative intensity): 71.0840 (2), 83.9540
acetate eluent.
2-(Thiophen-2-yl)-10H-phenothiazine (16) (Table 1,
entry 1).
Method 1 was applied to convert tributyl 2-
thienyl stannane and 2-chloro-10H-phenothiazine into the
title product in 4h. Purification by flash chromatography
(5% EtOAc/ 95% pet. ether eluent) supplied the analytically
pure yellow solid product (227.61mg, 81%), mp 188–189°C.
NMR: δH (400 MHz, acetone-d6): 7.80 (1H, br, s); 7.28–7.27
(1H, dd, J=7.27, 7.27); 7.22–7.20 (1H, d, J=7.21);
6.99–6.94 (2H, m); 6.89–6.86 (4H, m); 6.69–6.59 (2H, m).
δc (150MHz, acetone-d6): 144.35, 143.78, 142.90, 134.65,
129.01, 128.41, 128.28, 127.64, 127.20, 125.63, 123.95,
123.06, 120.20, 118.40, 118.17, 115.58, 112.37. UV-
Visible λmax (MeOH): 492.5 (4.03); 747.5 (3.99). HRMS
(EI), m/z (% relative intensity): 83.0773 (2.0), 118.5283
(3.0), 140.5161 (7.0), 167.0773 (2.0), 191.0729 (3.0),
204.0827 (13.0), 217.0921 (5.0), 236.0547 (23), 266.0150
(2.0), 281.0339 [(100), M+]. (Found: C, 68.37; H, 4.03; N,
5.01; S, 22.86%. Molecular formula C16H11NS2 requires C,
68.30; H, 3.94; N, 4.98; S, 22.79.)
6-(Thiophen-2-yl)-5H-benzo[a]phenothiazin-5-one
(17)
(Table 1, entry 2). Method 2 was used to convert tributyl
2-thienyl stannane and 6-chloro-5H-benzo[a]phenothiazin-
5-one into the title product within 6h. Purification by flash
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

E. A. Onoabedje, U.C. Okoro, and D. W. Knight
Vol 000
(100), 301.0420 (2), 330.0464 [(100), M+]. (Found: C,
69.11; H, 3.07; N, 8.51; S, 9.74%. Molecular formula
C19H10N2O2S requires C, 69.08; H, 3.05; N, 8.48; S,
(40 mL). Sodium dithionite (0.5 g) was added, and the
mixture was refluxed in a water bath for 1.5 h. During the
refluxing period, the color changed from red to yellow.
The entire mixture was poured into a solution containing
0.5 g of dithionite in 100mL of ice-cold water and
stirred. This was quickly filtered by suction, but before
the product could be collected from the filter paper, it had
turned reddish. Analysis of the product confirmed it to be
the starting iminoquinoid compound 17. This shows the
reduced compound was auto-oxidized under this
condition. Similar observations were seen in the case of
compounds 18, 19, 21, and 22.
9.70%.)
2-(Furan-2-yl)-10H-phenothiazine (20) (Table 1,
entry 5). Method 1 was used to convert tributyl furan-2-
yl stannane and 2-chloro-10H-phenothiazine into the title
product in 5h. Analytically pure product obtained by flash
chromatography (5% EtOAc/95% pet. ether eluent) as
yellow solid, yield 204mg (77%), mp 174–176°C. NMR:
δH (400MHz, acetone-d6): 7.83 (1H, br, s); 7.43–7.43 (1H,
dd, J= 7.43, 7.43); 7.01–6.98 (1H, dd, J=7.00, 7.00);
6.87–6.78 (3H, m); 6.67–6.56 (3H, m); 6.37–6.35 (1H, dd,
6.36, 6.36). δc (150MHz, acetone-d6): 154.19, 143.66,
143.39, 143.13, 142.98, 131.18, 128.39, 127.20, 123.02,
118.40, 118.20, 117.71, 115.57, 112.64, 110.33, 106.02.
UV-Visible λmax (MeOH): 747.0 (4.10). (Found: C, 72.47;
H, 4.22; N, 5.21; S, 12.06%. Molecular formula
Acknowledgments. We thank the Petroleum Technology Development
Funds (PTDF) for financial support and Cardiff University for a
short-term research opportunity.
C16H11NOS requires C, 72.43; H, 4.18; N, 5.28; S, 12.08.)
6-(Furan-2-yl)-5H-benzo[a]phenoxazin-5-one (21) (Table 1,
REFERENCES AND NOTES
entry 6). Method 2 was used to convert tributyl furanyl
stannane and 6-chloro-5H-benzo[a]phenoxazin-5-one into
the title product in 6 h. Analytically pure product was
provided by flash chromatography (10% EtOAc/90% pet.
ether eluent) as a dark brown solid, yield 210mg (67%),
mp 140–142°C. NMR: δH (400 MHz, CDCl3) 8.62–8.60
(1H, m); 8.27–8.24 (1H, m); 7.72–7.63 (3H, m); 7.59–
7.58 (1H, dd, J= 7.58, 7.58); 7.41–7.37 (1H, m); 7.30–
7.24 (3H, m); 6.55–6.54 (1H, dd, J =6.55). δc (150MHz,
CDCl3): 181.02 (C¼O), 146. 91, 146.11, 145.53, 144.06,
142. 61, 132.96, 131.99, 131.78, 131.32, 130.73, 129.54,
126.42, 125.34, 124.45, 116.13, 114.89, 111.40, 109.49.
UV-Visible λmax (MeOH): 447 (4.02). (Found: C, 72.62;
H, 4.22; N, 5.19%. Molecular formula C16H11NO2
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convert tributyl furanyl stannane and 6-chloro-5H-naphtho
[2,1-b]pyrido[2,3-e][1,4]oxazin-5-one to the title product
within 6h. Analytically pure product obtained by flash
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eluent as a dark brown solid, yield 220mg (70%), mp
210–212°C. NMR: δH (400MHz, CDCl3): 8.84–8.82 (1H,
m); 8.57– 8.56 (1H, dd, J=8.56, 8.56); 8.31–8.29 (1H,
m); 7.77–7.69 (3H, m); 7.62–7.61 (1H, dd, J=7.61, 7.61);
7.40–7.34 (2H, m); 6.59–6.58 (1H, dd, J=6.58, 6.58). δc
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(3.87). (Found: C, 72.83; H, 3.17; N, 8.78%. Molecular
formula C19H10N2O3 requires C, 72.61; H, 3.21; N, 8.91.)
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a reaction flask containing water (2 mL) and acetone
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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Rapid Access to New Angular Phenothiazine and Phenoxazine Dyes
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