Synthesis and reactions of some new benzo[a]phenothiazine-3,4-dione derivatives

Article abstract of DOI:10.1002/jhet.1061

The reaction of 2,3-dihydro-2,3-epoxy-1,4-naphthoquinone () with substituted anilines furnished the corresponding benzo[fused]heterocyclic derivatives. Furthermore, treatment of benzo[a]phenothiazine derivative with halo compounds, namely, ethyl bromoacetate, phenacyl bromide, dibromoethane, or chloroacetone afforded ether derivatives, respectively. Moreover, the reaction of with o-substituted aniline gave the corresponding benzo[a]phenothiazin-5-one derivatives and benzo[d][1,3]oxazin-4-one, respectively. Finally, the chromenone derivative was synthesized via the reaction of ester derivative with salicyaldhyde in refluxing pyridine. The newly synthesized compounds were characterized by spectroscopic measurements (IR, ¹H NMR, ¹³C NMR, and mass spectra).

Full text of DOI:10.1002/jhet.1061

Month 2013
Synthesis and Reactions of Some New Benzo[a]phenothiazine‐
3,4‐dione Derivatives
A. H. Abdel‐Rahman, E. M. Kandeel, M. A. Berghot,
*
and Marwa Abdel‐Motaal
Chemistry Department, Faculty of Science, Mansoura University, Mansoura 35516, Egypt
*
E-mail: dr_maroochem@yahoo.com
Received March 4, 2011
DOI 10.1002/jhet.1061
Published online 00 Month 2013 in Wiley Online Library (wileyonlinelibrary.com).
The reaction of 2,3‐dihydro‐2,3‐epoxy‐1,4‐naphthoquinone (4) with substituted anilines furnished the
corresponding benzo[fused]heterocyclic derivatives 5–8. Furthermore, treatment of benzo[a]phenothiazine
derivative 7 with halo compounds, namely, ethyl bromoacetate, phenacyl bromide, dibromoethane, or
chloroacetone afforded ether derivatives 11–14, respectively. Moreover, the reaction of 11 with o‐substituted
aniline gave the corresponding benzo[a]phenothiazin‐5‐one derivatives 15–17 and benzo[d][1,3]oxazin‐
4‐one18, respectively. Finally, the chromenone derivative 19 was synthesized via the reaction of ester
derivative 11 with salicyaldhyde in refluxing pyridine. The newly synthesized compounds were characterized
by spectroscopic measurements (IR, 1H NMR, 13C NMR, and mass spectra).
J. Heterocyclic Chem., 00, 00 (2013).
INTRODUCTION
state‐space and H∞ control [20]. A general theory of nonlinear
systems in the frequency domain has been proposed by Banks
[21]. Their method is based upon the extension of the Fourier
transform of the input–output map into a Taylor series in an
appropriate function space. Banks [22] and Sangelaji [23]
have studied the stabilization of a general class of nonlinear
systems by using the associated angular system and the
method designs a controller, which stabilizes the system by
converting the system to a spherical and a radial differential
system. The stabilization of an inverted pendulum via
the associated angular method has been studied by
Sangelaji and Banks [24].
Previously, aromatic bifunctionalized compounds and various
benzoannulated five‐, six‐ and seven‐membered heterocycles
were reported to posses promising biological activities [1, 2],
in particular, phenoxazine [3, 4], phenazine [5, 6], pheno-
thiazine [7, 8], and naphthoxazipine [9] derivatives. There-
fore, number of methods has been developed for the
preparation of these derivatives [10–13]. On the other hand,
epoxy‐1,4‐naphthoquinone is an important intermediate in
the synthesis of several biologically active compounds
[14–17]. However, the reaction of bifunctionalized aromatic
compounds with epoxy naphthoquinone has not been
studied before. We report herein the scope and applicability
of 2,3‐epoxy‐2,3‐dihydro‐1,4‐naphthoquinone (4) as a unique
precursor for the synthesis of some condensed heterocycles
and their behavior toward different reagents in which a
quinone ring is incorporated.
RESULTS AND DISCUSSION
Based on the chemistry of 2,3‐dihydro‐2,3‐epoxy‐1,4‐
naphthoquinone (4) [18–20], different benzo[c]phenoxazine,
benzo[a]phenazine, and benzo[a]phenol‐thiazine derivatives
were synthesized as outlined in Schemes 1–4. It was reported
that the reaction of 2,3‐dichloronaphthoquinone with
o‐aminophenol [21–23] in pyridine afforded the 6H‐benzo
Control design for nonlinear systems has been developed
in recent years leading to many different methods, including
linearization [18], sliding mode control [19], and optimal
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A. H. Abdel-Rahman, E. M. Kandeel, M. A. Berghot, and M. Abdel-Motaal
Vol 000
[b]phenoxazine‐6,11(12H)‐dione (1). In addition, condensation
of 2,3‐dichloronaphthoquinone with aromatic thiols
[21, 24, 25] or aromatic amines in NaN3/DMF [26–27]
afforded the linear heterocyclic quinones 2 and 3,
respectively (Fig. 1).
The purpose of this work is to synthesize these
linear naphthoquinones using 2,3‐dihydro‐2,3‐epoxy‐1,4‐
naphthoquinone involving a novel heterocyclization proce-
dure in high yield. But unexpectedly, the data of the synthe-
sized compounds were not compatible with the reported data
of these known linear heterocyclic quinones. In view of this
purpose and with the spectral data of the formed products,
the products were seemed to be the angular heterocyclic
quinones (Scheme 1).
Condensation of 4 with o‐substituted‐aniline deriv-
atives namely; o‐aminophenol, o‐phenylenediamines,
o‐aminothiophenol, and o‐aminobenzoic acid in ethanol
afforded the corresponding benzo[c]phenoxazinedione,
benzophenazinedione, benzo[a]phenothiazinedione, and
naphtho[4,3‐b][1,4]oxazepine‐1,2,6(9H)‐trione derivatives 5–8,
respectively. The proposed mechanism for the formation of
these angular compounds involves nucleophillic attack at C3
with the opening of the epoxide ring yielded the expected
intermediate 9. Subsequent oxidation and cyclization formed
the fully aromatized angular compounds 5–8 (Scheme 2).
The enole tautomer is expected to be more stable than the
keto one. This was revealed from the results of ab initio/3‐21G
molecular orbital calculations that were carried out, in vacuo,
individually on the two tautomers. Results from Table 1
showed that the total energy of the enol form has lower value
than that of the keto form (more negative by about 6.0 Kcal/
mole, which is an indication for relative stability). Moreover,
the energy difference between the highest occupied molecu-
lar orbital (HOMO) and lowest unoccupied molecular orbital
(LUMO) is higher in case of the enol form than in the keto
form (indication for relative stability). The calculated molec-
ular dipole moment is lower in case of the enol form than in
the keto form (4.159 and 9.469 D, respectively).
As thiols are more reactive nucleophile than amines [28],
it should be expected that o‐aminothiophenol would attack
the epoxide ring through thiol function leading to 7 as final
product. The thiazinone 7 can exist in two tautomeric forms
7a and 7b, and it appears to be identical with the thiazinone
derived previously from o‐aminothiophenol with 3‐chloro‐1,2‐
naphthoquinone, 3‐chloro‐2‐hydroxy‐1,4‐naphthoquinone, or
2‐hydroxy‐1,4‐naphthoquinone [29]. Thus, it was found that
the reaction of α‐haloketones and dibromoethane with 7
favored the enol form rather than NH to give the more
stable 1,4‐quinone derivatives 11–14 (Fig. 2).
The evidence for this postulate was developed from the
IR spectrum of 11 which showed stretching absorption
bands at 3284 and 1617 cm−1 due to (NH) and (CO)
groups, respectively. Moreover, the 13C NMR spectrum
of 11 revealed the presence of signals at 13.96 (CH3),
60.55 (COOCH2), and 68.042 (OCH2); this suggested the
presence of C-O bond rather than C-N bond. Furthermore,
the 1H NMR spectrum showed absence of singlet signal at
δ 9.6 ppm due to NH proton. The mass spectrum showed
the molecular ion peak at m/z 365 (M+, 33.7).
It was reported that benzo[a]phenothiazine has a number of
physicochemical [30] and biochemical studies [31, 32],
and they present interesting spectroscopic [33–34] and
photophysical [35, 36] properties. In view of these observa-
tions, compound 7 was used as a building block for the synthe-
sis of other derivatives [37]. Subsequent alkylation of 7 with
α‐haloketones, namely, ethyl bromoacetate, chloroacetone,
and phenacyl bromide in boiling acetone in the presence
of K2CO3 afforded the corresponding alkylated benzo[a]
phenothiazine‐3‐one derivatives 11–14, respectively, in
high yields. On a similar manner, reaction of 7 with 1,2‐
dibromoethane in acetone and potassium carbonate afforded
Figure 1. Linear heterocyclic quinones 1–3.
Scheme 1. Reaction of ethyl naphtho[2,3‐b]oxirene‐2,7(1aH,7aH)‐dione (4) with substituted anilines.
Journal of Heterocyclic Chemistry
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Month 2013
Synthesis and Reactions of Some New Benzo[a]phenothiazine-3,4-dione Derivatives
Scheme 2. Mechanism of formation of benzo[c]phenoxazinedione, benzophenazinediones, benzo[a]phenothiazinedione, and naphtho[4,3‐b][1,4]
oxazepine‐1,2,6(9H)‐trione derivatives 5–8.
Table 1
Quantum mechanical data obtained from PM3 semiempirical MO and ab initio (3‐21G) calculations of the configurations of 7a and 7b.
Method
Binding energy (Kcal/mol)
ΔE (LUMO–HOMO)
Dipole moment (D)
7a
PM3
−3482.66
6.6534 Kcal/mol
−7.5259 − (0.6941) = 6.8318 eV
6.513
7.946
Ab initio (3‐21G)
7b
PM3
Ab initio (3‐21G)
−756947.595
−3480.125
−756953.6
6.9691 Kcal/mol
−7.9829 − (0.7053) = 7.2776 eV
2.882
4.159
the corresponding benzo[a]phenothiazine derivative 13 in
92% yield (Scheme 3).
compound 14 singlet signals appeared at δ 2.1 and 5.1 ppm
for CH3 and CH2 protons, respectively. The H NMR
1
In addition, the structures of compounds 12–14 were
established on the basis of elemental analyses and spectral
data. The IR spectrum of compounds 12–14 revealed the
absence of (NH) group. The 1H NMR spectrum of 12 revealed
singlet signal at δ 6.0 ppm due to methylene protons, while for
spectrum of 13 showed signal at 4.6 ppm (dd, 4H,
2CH2). The mass spectra of 12–14 showed the molecular
ion peaks at m/z 397 (M+, 13%), 584 (M+, 6.9%), and
336 (M+ + 1, 3.7%), respectively.
The ethyl ester 11 served as a good precursor for the syn-
thesis of heterocycles attached to the benzonaphthoquinone
moiety. For compounds 15–19, the ethyl ester derivative
was fused with o‐aminophenol or o‐aminothiophenol in the
presence of potassium carbonate to give the desired products
benzoxazole derivative 15 and benzothiazol derivative 16,
respectively, in 40–50% yield. Compound 15 was also pre-
pared from the reaction of the ethyl ester 11 and o‐
aminophenol in boiling toluene in the presence of potas-
sium carbonate. Indication of the structures 15 and 16
are based on the elemental analyses and spectral data.
The IR and 1H NMR spectra of compounds 15 and 16 re-
vealed the disappearance of ester group.
Under the same conditions, cyclocondensation of the
ethyl ester 11 with the o‐phenylenediamine derivative gave
the corresponding benzimidazol derivative 17 in 58% yield.
The IR spectrum showed bands at 3438 (NH) and 1633,
1
1589 (2C═O). The H NMR spectrum of 17 revealed the
disappearance of signals corresponding to ester protons
Figure 2. The enole‐keto tautomers of the configurations 7a,b.
and revealed singlet signals at δ 5.082 and 5.2 ppm for
Journal of Heterocyclic Chemistry
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A. H. Abdel-Rahman, E. M. Kandeel, M. A. Berghot, and M. Abdel-Motaal
Vol 000
Scheme 3. Reaction of 7 with different halogenated compounds.
CH2 and NH protons, respectively. In addition, the mass
spectrum showed the molecular ion peak at 513 (M+, 18).
Also, the benzoxazinone derivative 18 was synthesized
by the fusion of 11 with anthranilic acid. The IR spectrum
of 18 showed bands at 1700 (C═O, cyclic ester), 1666,
1623 (2C═O), and 1587 cm−1 (C═N), while the 1H
NMR spectrum revealed singlet signal at δ 6.1 ppm due
to methylene protons.
Knoevenagel reaction of active methylene esters with o‐
hydroxyaldehydes was reported as facile synthesis con-
densed α‐pyranones and coumarines [38]. Thus, the ester
11 underwent cyclocondensation with salicylaldehyde in
refluxing pyridine to afford the corresponding coumarine
derivative 19 in 88% yield. Compound 19 was established
in the bases of elemental analysis and spectral data. The 1H
NMR spectrum of 19 revealed the absence of methylene
and ester protons (Scheme 4).
EXPERIMENTAL
All melting points are recorded on Gallenkamp electric melting
point apparatus and are uncorrected. The IR spectra υ′ (cm−1) (KBr)
were recorded on a Perkin Elmer Infrared Spectrophotometer
1
Model 157 at Faculty of Science, Mansoura University. The H
NMR and 13C NMR spectra were recorded on a Varian 300 MHz
spectrometer using the indicated solvents using TMS as an internal
reference (Faculty of Science, Cairo University, Egypt). The mass
spectra (EI) were recorded on 70 eV with Kratos MS equipment
at the Microanalytical Center (Faculty of Science, Cairo University,
Egypt). Elemental analyses (C, H, and N) were carried out at
the Microanalytical Center of Cairo University (Giza, Egypt).
Scheme 4. Reaction of ethyl 2‐(5‐oxo‐5H‐benzo[a]phenothiazin‐6‐yloxy)acetate (11) with 1,2‐substituted benzene derivatives.
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Month 2013
Synthesis and Reactions of Some New Benzo[a]phenothiazine-3,4-dione Derivatives
2,3‐Dihydro‐2,3‐epoxy‐1,4‐naphthoquinone (4) was prepared
according to the previously reported methods [22, 25].
Reaction of 2,3‐dihydro‐2,3‐epoxy‐1,4‐naphthoquinone (4)
with substituted‐aniline derivatives: General procedure. A
mixture of 2,3‐dihydro‐2,3‐epoxy‐1,4‐naphthoquinone (4) (1.7
g, 10 mmol) and substituted aniline derivatives, namely, o‐
aminophenol (1.1 g, 10 mmol), o‐phenylenediamine (1 g, 10
mmol), 3,4‐diaminobenzophenone (2.1 g, 10 mmol), o‐
aminothiophenol (1.2 g, 10 mmol), or o‐aminobenzoic acid
(1.4 g, 10 mmol) in ethanol (15 mL) was refluxed for 30 min up
to 1 h. The reaction mixture was left to cool. The separated solid
was filtered off, dried, and recrystallized from ethanol to afford
compounds 5–8, respectively.
5H‐Benzo[c]phenoxazine‐5,6(7H)‐dione (5). Deep blue crystals,
Yield, 95%, mp: 150°C; IR (KBr): νmax, cm−1: 3307 (NH),
1648, 1614 (C═O); 1H NMR (DMSO): δ 6.6–7.9 (m, 8H,
Ar‐H), 9.6 (s, 1H, NH); MS: m/z (%) = 265 (M+ + 2, 3.3), 213
(24.7), 104 (42.0), 78 (46), 44 (100.0). Anal. Calcd for
C16H9NO3 (263.25): C, 73.00; H, 3.45; N, 5.32%. Found: C,
73.12; H, 3.51; N, 5.38%.
Ethyl 2‐(5‐oxo‐5H‐benzo[a]phenothiazin‐6‐yloxy)acetate
(11). Reaction time 3 h, red needles, Yield, 91%; mp: 169–170°
C, crystallization from ethanol, IR (KBr): νmax, cm−1: 2939 (CH,
aliphatic), 1617 (C═O), 1751 (C═O, ester), 1214 (C-O, stretch);
1H NMR (DMSO): δ 1.2 (t, 3H, CH2CH3), 4.1 (q, 2H,
CH2CH3), 5.1 (s, 2H, N-CH2), 7.5‐8.8 (m, 8H, Ar‐H). 13C NMR
(DMSO): δ 13.96 (CH3), 60.5 (COOCH3), 68.04 (OCH2), 124.9,
125.1, 125.4, 125.7, 126.5, 128.04, 129.3, 131.5, 131.6, 132.7,
165.07, 168.47, 173.3, 174; MS: m/z (%) = 365 (M+, 33.7), 292
(62.0), 322 (13.6), 250 (100.0), 278 (19.0). Anal. Calcd for
C20H15NO4S (365.40): C, 65.74; H, 4.14; N, 3.83%. Found: C,
65.85; H, 4.20; N, 3.88%.
6‐(2‐Oxo‐2‐phenylethoxy)‐5H‐benzo[a]phenothiazin‐5‐one
(12). Reaction time 5 h, purple crystals, Yield, 95 %, mp: 211°
C, crystallization from ethanol, IR (KBr): νmax, cm−1: 2923
(CH, aliphatic), 1672, 1660 (2C═O), 1625 (C═N), 1192
(C-O, stretch). 1H NMR (DMSO): δ 6.0 (s, 2H, N-CH2),
7.4–8.9 (m, 13H, Ar‐H); MS: m/z (%) = 397 (M+, 13), 292
(62), 278(12.2), 250(88), 190(17), 105(100). Anal. Calcd
for C24H15NO3S (397.45): C, 72.53; H, 3.80; N, 3.52%.
Found: C, 72.59; H, 3.84; N, 3.57%.
Benzo[a]phenazine‐5,6(7H,12H)‐dione (6a). Deep blue crystals,
Yield, 90%, mp: 257°C, IR (KBr): νmax, cm−1: 3367 (2NH),
1648 (2C═O); 1H NMR (DMSO): δ 7.5–9.5 (m, 8H, Ar‐H),
10.1 (s, 1H, NH), 11.0 (s, 1H, NH); MS: m/z (%) = 265 (M+ +
3, 100.0), 234 (26.8), 205 (23.0). Anal. Calcd for
C16H10N2O2 (262.26): C, 73.27; H, 3.84; N, 10.68%. Found:
C, 73.31; H, 3.88; N, 10.72%.
6,60‐(Ethane‐1,2‐diylbis(oxy))bis(5H‐benzo[a]phenothiazin‐
5‐one) (13). Reaction time 3 h, green crystals, Yield, 92%, mp:
242°C, crystallization from acetone, IR (KBr): νmax, cm−1
:
2923 (CH, aliphatic), 1631, 1610 (2C═O), 1585 (C═N), 1231
(C-O, stretch). 1H NMR (DMSO): δ 4.6 (t, 4H, 2CH2), 7–8.5
(m, 16H, Ar‐H); 13C NMR (DMSO): δ 178.3, 177.9, 166.3,
165.1, 159.2, 158.8, 147.8, 147.0, 137.2, 136.0, 135.3, 135.0,
132.6, 132.4, 131.8, 131.3, 131.0, 130.8, 130.7, 130.1, 129.7,
129.6, 128.1, 127.6, 127.3, 124.3, 124.2, 123.0, 122.8, 110.9,
109.6, 67.9, 67.1, 66.0. MS: m/z (%) = 584 (M+, 6.9), 292
(3.2), 379(100), 146(19.5), 121(36). Anal. Calcd for
C34H20N2O4S2 (584.66): C, 69.85; H, 3.45; N, 4.79%. Found:
C, 69.93; H, 3.52; N, 4.84%.
6‐(2‐Oxopropoxy)‐5H‐benzo[a]phenothiazin‐5‐one (14).
Reaction time 2 h, deep violet crystals, Yield, 62%, mp: 191°C,
crystallization from acetonitrile, IR (KBr): νmax, cm−1: 2919 (CH,
aliphatic), 1772, 1610 (2C═O), 1590 (C═N), 1217 (C-O, stretch).
1H NMR (DMSO): δ 2.1 (s, 3H, CH3), 5.1 (s, 2H, CH2), 7.5–8.8
(m, 8H, Ar‐H). MS: m/z (%) = 336 (M+ + 1, 3.7), 292 (44.9), 278
(4.6), 263(13.4), 250 (100), 190 (33.1). Anal. Calcd. for
C19H13NO3S (335.38): C, 68.04; H, 3.91; N, 4.18%. Found: C,
68.08; H, 3.97; N, 4.23%.
Reaction of 11 with o‐substituted anilines: General
procedure. A mixture of ester 11 (1.07 g, 3 mmol) and o‐
substituted aniline derivatives, namely, o‐aminophenol (0.33 g,
3 mmol), o‐aminothiophenol (0.38 g, 3 mmol), 3‐benzoyl‐1,2‐
phenylenediamine (0.34 g, 3 mmol), or anthranilic acid (0.41 g, 3
mmol) was fused at 150 and 170°C in case of reaction with 3‐
benzoyl‐1,2‐phenylenediamine in oil bath for the appropriate
reaction time. The fused solid was left to cool then the formed
solid product was collected and recrystallized from ethanol to
afford benzo[a]phenothiazinone derivatives 15–17 and benzo[d]
[1,3]oxazinone derivative 18, respectively.
9‐Benzoylbenzo[a]phenazine‐5,6(7H,12H)‐dione (6b). Yellow
crystals, Yield, 86%, mp: >300°C, IR (KBr): νmax, cm−1: 3415,
1
3390 (2NH), 1650, 1598 (3C═O); H NMR (DMSO): δ 7.6–8.6
(m, 12H, Ar‐H), 9.2 (s, 2H, 2NH); MS: m/z (%) = 366 (M+, 2), 234
(5.6), 212 (99.0), 135 (100.0). Anal. Calcd for C23H14N2O3
(366.37): C, 75.40; H, 3.85; N, 7.65%. Found: C, 75.37; H, 3.81;
N, 7.69%
5H‐Benzo[a]phenothiazine‐5,6(12H)‐dione (7). Deep violet
crystals, Yield, 96%, mp: 286°C (lit. [32], 270–272), IR (KBr):
1
ν
max, cm−1: 3284 (NH), 1617, 1596 (2CO). H NMR (DMSO):
δ 7.4–8.83 (m, 8H, Ar‐H), 11.2 ppm (s, 1H, NH); MS: m/z (%)
= 280 (M+ + 1, 100.0), 264 (66.6), 105 (50.8), 63 (73.0). Anal.
Calcd for C16H9NO2S (279.31): C, 68.80; H, 3.25; N, 5.01%.
Found: C, 68.87; H, 3.32; N, 5.08%.
Benzo[e]naphtho[1,2‐b][1,4]oxazepine‐5,6,12(7H)‐trione (8).
Deep blue crystals, Yield, 88%, mp: 250°C, IR (KBr): νmax, cm−1:
3334 (NH), 1683, 1637 (3C═O); 1H NMR (DMSO): δ 6.6–7.9 (m,
8H, Ar‐H), 9.6 (s, 1H, NH); 13C NMR (DMSO): δ 186.7, 181.4,
164.3, 155.2, 148.7, 134.7, 134.3, 134.2, 133.1, 131.6, 129.5, 129.0,
128.6, 128.5, 122.3, 120.1, 118.9, 109.7; MS: m/z (%) = 292 (M+ +
1, 100.0), 227 (15), 235 (50), 159 (65), 156 (88), 91 (15). Anal.
Calcd for C17H9NO4 (291.26): C, 74.18; H, 3.30; N, 5.09%. Found:
C, 74.23; H, 3.36; N, 5.14%.
Reaction of benzo[a]phenothiazine derivative 7 with halo
compounds: General procedure. A mixture of 7 (1.4 g, 5
mmol) and halo compounds, namely, ethyl bromoacetate (0.84
g 5 mmol), phenacylbromide (1 g, 2.8 mmol) dibromoethane
(0.47 g, 2.5 mmol), or chloroacetone (0.53 g, 2.8 mmol) in
acetone (20 mL) in the presence of potassium carbonate (0.39
g) was refluxed on water bath for the appropriate time (2–5 h).
The reaction mixture was left to cool and the formed precipitate
was collected by filtration, washed with cold water, dried in
vacuo and crystallized from the appropriate solvent to afford
compounds 11–14, respectively.
6‐(Benzo[d]oxazol‐2‐ylmethoxy)‐5H‐benzo[a]phenothiazin‐
5‐one (15). Reaction time 1 h, violet crystals, Yield, 40%, mp:
234°C, IR (KBr): νmax, cm−1: 2923 (CH, aliphatic), 1616
1
(C═O), 1594, 1560 (2C═N); H NMR (DMSO): δ 6.3 (s, 2H,
OCH2), 7.0–8.0 (m, 12H, Ar‐H); MS: m/z (%) = 410 (M+,
21.2), 291 (28.0), 278 (26.0), 118 (13.7), 77 (100.0). Anal.
Calcd for C24H14N2O3S (410.44): C, 70.23; H, 3.44; N,
6.83%. Found: C, 70.18; H, 3.41; N, 6.78%.
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A. H. Abdel-Rahman, E. M. Kandeel, M. A. Berghot, and M. Abdel-Motaal
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6‐(Benzo[d]thiazol‐2‐ylmethoxy)‐5H‐benzo[a]phenothiazin‐
5‐one (16). Reaction time 1 h, deep violet crystals, Yield, 50%,
mp: 218°C, IR (KBr): νmax, cm−1: 1616 (C═O), 1592, 1560
(C═N); 1H NMR (DMSO): δ 5.2 (s, 2H, OCH2), 7.4–8.0 (m,
12H, Ar‐H); MS: m/z (%) = 426 (M+, 5.9), 368 (100), 336 (15.4),
292 (12), 162 (52.4). Anal. Calcd for C24H14N2O2S2 (426.51): C,
67.58; H, 3.31; N, 6.57%. Found: C, 67.63; H, 3.37; N, 6.61%.
6‐((5‐Benzoyl‐1H‐benzo[d]imidazol‐2‐yl)methoxy)‐5H‐benzo
[a]phenothiazin‐5‐one (17). Reaction time 2 h, deep red crystals;
58% yield; mp 156°C; IR (KBr): νmax, cm−1: 3438 (NH), 1722,
1689, 1633 (3C═O), 1523 (C═N); 1H NMR (DMSO): δ 5.0
(s, 2H, CH2), 5.2 (s, 1H, NH), 7.4–8.2 (m, 17H, Ar‐H); MS: m/z
(%) = 513 (M+, 18), 408 (20), 278 (65), 235 (33), 116 (46), 105
(80). Anal. Calcd for C31H19N3O3S (513.57): C, 72.50; H, 3.73;
N, 8.18%. Found: C, 72.56; H, 3.81; N, 8.24%.
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54, 978.
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Huang, H.‐S.; Chen, I.‐S. Phytochem 2007, 68, 1338.
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Printice‐Hall: London, 1988.
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Springer‐Verlag: Berlin, 1992.
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Eur J Med Chem 2009, 44, 3130.
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1962, 28, 520.
2‐((5‐Oxo‐5H‐benzo[a]phenothiazin‐6‐yloxy)methyl)‐4H‐
benzo[d][1,3]oxazin‐4‐one (18). Reaction time 2 h, reddish brown
crystals; 66%; mp 240°C; IR (KBr): νmax, cm−1: 1700 (C═O,
cyclic ester), 1666, 1623 (2C═O), 1587 (C═N); 1H NMR
(DMSO): δ 6.1 (s, 2H, CH2), 7.7–8.0 (m, 12H, Ar‐H); MS:
m/z (%) = 438 (M+, 39.0), 292 (100.0), 279 (34.0), 250
(60.1), 145 (29.0). Anal. Calcd for C25H14N2O4S (438.45): C,
68.48; H, 3.22; N, 6.39%. Found: C, 68.54; H, 3.28; N, 6.46%.
Synthesis of 6‐(2‐oxo‐2H‐chromen‐3‐yloxy)‐5H‐benzo[a]
phenothiazin‐5‐one (19). Equimolar amounts of the acetate ester
11 (1.07 g, 3 mmol) and salicylaldehyde (0.43 g, 3.5 mmol) in
pyridine (15 mL) was refluxed for 15 h. The separated solid
obtained during the course of the reaction, was filtered while
hot, dried and then recrystallized from acetone to give 19.
Reddish brown crystals, Yield, 88%, mp: >300°C; IR (KBr):
ν
max, cm−1: 1690 (C═O, cyclic ester), 1664 (C═O), 1610
1
(C═N); H NMR (DMSO): δ, 7.1–8.05 (m, 13H, Ar‐H); MS:
m/z (%) = 424 (M+ + 1, 39.0), 262 (100.0), 145 (25.0), 108
(44.1). Anal. Calcd for C25H13NO4S (423.44): C, 70.91; H,
3.09; N, 3.31%. Found: C, 70.96; H, 3.15; N, 3.38%.
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Soc Perkin Trans 1 1986, 2233.
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Nowacki, J. Chem Phys 1999, 249, 49.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet