Synthesis of new 2-phenylpyrano[3,2-b]phenothiazin-4(6H)-one derivatives

Article abstract of DOI:10.1002/cjoc.201100033

A new synthesis of 2-phenylpyrano[3,2-b]phenothiazin-4(6H)-one derivatives was reported. First 2,10-diacetyl-3-hydroxyphenothiazine (2) was converted into their benzoyloxy esters (3a-3j) using different aromatic carboxylic acids in the presence of phosphorous oxychloride in pyridine. Benzoyloxy esters were converted into their 1,3-diones (4a-4j) by using dry KOH in pyridine via Baker-Venkataraman transformation reaction. The 1,3-diones thus obtained were cyclised to pyranophenothiazines (5a-5j) by refluxing in an acetic acid/HCl mixture. A new synthesis of 2-phenylpyrano[3,2-b]phenothiazin-4(6H)-one derivatives was reported. First 2,10-diacetyl-3-hydroxyphenothiazine was converted into benzoyloxy esters using different aromatic carboxylic acids in the presence of phosphorous oxychloride. The benzoyloxy esters were converted into their 1,3-diones by using dry KOH in pyridine via Baker-Venkataraman transformation reaction. The 1,3-diones thus obtained were cyclised to pyranophenothiazines by refluxing in an acetic acid/HCl mixture. Copyright

Full text of DOI:10.1002/cjoc.201100033

FULL PAPER
Synthesis of New 2-Phenylpyrano[3,2-b]phenothiazin-
4(6H)-one Derivatives
Bansode, Tanaji N.*,a
Meshram, Gangadhar A.b
a Department of Chemistry, B. N. N. College, Bhiwandi, Thane (M.S.) 421 305, India
bDepartment of Chemistry, University of Mumbai, Santacruz (East), Mumbai 400 098, India
A
new synthesis of 2-phenylpyrano[3,2-b]phenothiazin-4(6H)-one derivatives was reported. First
2,10-diacetyl-3-hydroxyphenothiazine (2) was converted into their benzoyloxy esters (3a— 3j) using different aro-
matic carboxylic acids in the presence of phosphorous oxychloride in pyridine. Benzoyloxy esters were converted
into their 1,3-diones (4a— 4j) by using dry KOH in pyridine via Baker-Venkataraman transformation reaction. The
1,3-diones thus obtained were cyclised to pyranophenothiazines (5a— 5j) by refluxing in an acetic acid/HCl mix-
ture.
Keywords acetyl phenothiazine, Baker-Venkataraman transformation, 1,3-diones, pyranones, pyranophenoth-
iazine
Introduction
ment of conditions arising from capillary bleeding due
to increased capillary fragility.
The phenothiazines, exemplified by chlorpromazine,
are the largest and most widely investigated class of
neuroleptic agents.1,2 Phenothiazines form an important
class of heterocyclic compounds possessing wide spec-
trum diverse biological activities like antimicrobial,3,4
antimalarial,5 anti-inflammatory,6 antitubercular,7,8 an-
tipsychotic,9 etc. The phenothiazines contain an interest-
ing heterocyclic ring skeleton with two carbocyclic/
aromatic rings connected to each other via a sulfide and
an imino bridge which facilitates several types of reac-
tions, substitution at the nitrogen, electrophilic substitu-
tion on the aromatic rings, N-oxidation and photo-
chemical reactions,10,11 etc. Due to the increased impor-
tance of these heterocyclic compounds, attempts were
made during the past few years in the synthesis of new
generation of 10H-phenothiazines that exert their bio-
logical activity through modulation.12-14
Chromones constitute one of the major classes of
naturally occurring compounds, and interest in their
chemistry continues unabated because of their useful-
ness as biologically active agents.15,16 Chromones found
in the nature are 2-phenyl chromones, called flavones. A
considerable number of 3-phenyl chromones are also
known, called isoflavones. Some of the biological ac-
tivities attributed to chromone derivatives include cyto-
toxic,17,18 neuroprotective,19 HIV-inhibitory,20 anti-
microbial,21,22 antifungal23 and antioxidant activity.24
Due to their abundance in plants and their low mam-
malian toxicity, chromone derivatives are present in
large amounts in the diet of humans.25 Flavones possess
vitamin P activity26 and therefore are used in the treat-
The synthesis of chromone derivatives is a research
field of great interest and long history.27 In general,
chromones are synthesized by the cyclodehydration of
1-(o-hydroxyaryl)-1,3-diketones or equivalent interme-
diates catalyzed by strong acids or strong bases (Vils-
meier-Haack reaction).28-30 They have been prepared on
a large scale by the Allan-Robinson synthesis involving
acylation-rearrangement, and subsequent cyclization.31
This methodology has been followed in the synthesis of
chromone derivatives with quaternary ammonium func-
tionalities which show not only activity of cosmetic in-
terest but also for hair sustainability, as well as in the
asymmetric synthesis of optically active 4-chromone
derivatives.32,33 In the Baker-Venkataraman synthe-
sis,34-36 internal Claisen condensation of 2-aryloxy-1-
acetylarenes is employed as the key step. More recently,
the synthesis of chromone derivatives was accomplished
by intramolecular ester carbonyl olefination37 or
Pd-catalyzed regiospecific carbonylative annulation of
o-iodophenol acetates and acetylenes.38,39
The various physiological and biological activities of
2-phenyl chromones and phenothiazines prompted the
synthesis of new pyranophenothiazines. Keeping these
factors in view it was thought worthwhile to prepare
chromones with different substituents in phenyl nucleus
and benzenoid nucleus. Also as the part of our research
in the synthesis of biological active heterocyclic com-
pound3,4,40,41 and their cyclization via ring closure reac-
tion, the present work was aimed to synthesize some
new chromones with phenothiazine moiety.
*
E-mail: bansodeaditya@yahoo.co.in, meshramga@chem.mu.ac.in
Received June 20, 2011; revised July 6, 2011; accepted July 11, 2011.
Chin. J. Chem. 2011, 29, 1917— 1921
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
1917

Bansode & Meshram
FULL PAPER
Experimental
2,10-Diacetyl-3-(3-chlorobenzoyloxy)phenothia-
1
zine (3c) Yield 88%, m.p. 147—149 ℃; H NMR
All chemicals were purchased from Aldrich and
Merck Ltd, Mumbai (India), and were used without
further purification. The melting points were determined
in open capillaries using a Toshniwal melting point ap-
paratus and are uncorrected. The IR spectra were re-
corded in the solid state as a KBr suspension on an
Perkin-Elmer Spectrum One FT-IR spectrophotometer
(CDCl3) δ: 8.14—6.91 (m, 10H, Ar-H), 2.52 (s, 3H,
COCH3), 2.11 (s, 3H, COCH3); IR (KBr) ν: 1673, 1724,
1735 (C＝O), 2868, 2933 (CH2), 3063 (Ar-H); MS m/z
(%): 437 [M＋] (84), 394 (100), 255 (72). Anal. calcd for
C23H16ClNO4S: C 63.08, H 3.68, N 3.20; found C 63.21,
H 3.55, N 3.03.
2,10-Diacetyl-3-(4-chlorobenzoyloxy)phenothia-
1
and H NMR and 13C NMR spectra were obtained in
1
zine (3d) Yield 89%, m.p. 170—172 ℃; H NMR
CDCl3 on a Brucker 300 MHz instrument using TMS as
an internal standard. Mass spectra were recorded on a
LCQ Adavantage Thermo Finnigen spectrometer. Ele-
mental analysis was performed on Carlo Erba 1108
analyzer
(CDCl3) δ: 8.04—6.79 (m, 10H, Ar-H), 2.51 (s, 3H,
COCH3), 2.10 (s, 3H, COCH3); IR (KBr) ν: 1675, 1725,
1736 (C＝O), 2870, 2934 (CH2), 3065 (Ar-H); MS m/z
(%): 437 [M＋] (86), 394 (100), 255 (74). Anal. calcd for
C23H16ClNO4S: C 63.08, H 3.68, N 3.20; found C 63.20,
H 3.56, N, 3.09.
Synthesis of 2,10-diacetyl-3-hydroxyphenothiazine (2)
2,10-Diacetyl-3-(2-methylbenzoyloxy)phenothia-
To the solution of 10-acetyl 3-methoxy phenothia-
zine 1 (0.01 mol) in carbon disulphide (50 mL), acetyl
chloride (0.02 mol) and anhydrous aluminium chloride
(0.025 mol) were added at 0—10 ℃. The reaction mix-
ture was refluxed under stirring for 5 h. Then resulting
mixture was distilled off and poured on ice cold dil HCl.
The solid thus obtained was filtered and washed with
cold alcohol. The yellow solid was crystallized from
1
zine (3e) Yield 89%, m.p. 140—142 ℃; H NMR
(CDCl3) δ: 8.03—6.78 (m, 10H, Ar-H), 2.50 (s, 3H,
COCH3), 2.34 (s, 3H, CH3), 2.10 (s, 3H, COCH3); IR
(KBr) ν: 1673, 1724, 1735 (C＝O), 2869, 2933 (CH2),
3064 (Ar-H); MS m/z (%): 417 [M＋] (80), 374 (100),
255 (70). Anal. calcd for C24H19NO4S: C 69.05, H 4.59,
N 3.36; found C 69.18, H 4.66, N 3.29.
1
2,10-Diacetyl-3-(4-methoxybenzoyloxy)phenothia-
alcohol to afford 2. Yield 80%, m.p.170—172 ℃; H
1
zine (3j) Yield 87%, m.p. 194—196 ℃; H NMR
NMR (CDCl3) δ: 7.58—7.02 (m, 6H, Ar-H), 5.06 (s, 1H,
OH), 2.52 (s, 3H, COCH3), 2.10 (s, 3H, COCH3); IR
(KBr) ν: 1646, 1683 (C＝O), 2862, 2936 (CH2), 3067
(Ar-H); MS m/z (%): 299 [M＋] (45), 256 (100), 213
(20). Anal. calcd for C16H13NO3S: C 64.20, H 4.38, N
4.68; found C 64.13, H 4.46, N 4.59.
(CDCl3) δ: 8.04—6.79 (m, 10H, Ar-H), 3.74 (s, 3H,
OCH3), 2.51 (s, 3H, COCH3), 2.08 (s, 3H, COCH3); IR
(KBr) ν: 1676, 1729, 1739 (C＝O), 2867, 2931 (CH2),
3062 (Ar-H); MS m/z (%): 433 [M＋] (82), 390 (100),
255 (74). Anal. calcd for C24H19NO5S: C 66.50, H 4.42,
N 3.23; found C 66.58, H 4.56, N 3.29.
General procedure for synthesis of esters 3a— 3j
General procedure for synthesis of 1,3-diketones 4a
— 4j
2,10-Diacetyl-3-hydroxyphenothiazine (2) (0.005
mol) and benzoic acid (0.005 mol) were dissolved in
pyridine (5 mL) and cooled in ice bath. To this cold so-
lution phosphorous oxychloride (0.01 mol) was added
slowly with constant stirring. Then the reaction mixture
was stirred at room temperature for 3—4 h. The reaction
mixture was poured on crushed ice with HCl and crude
precipitate was filtered to afford 3a. Similarly, com-
pounds 3b—3j were synthesized by using different sub-
stituted benzoic acid.
A mixture of 2,10-diacetyl-3-benzoyloxypheno-
thiazine (3a) (0.001 mol), dry pyridine (5 mL) and
powdered KOH (0.002 mol) was stirred for 1 h. After
stirring reaction mixture was poured on ice cold water
and HCl, the solid thus obtained was filtered and
washed with water and recrystallized from aqueous al-
cohol to give 4a. Similarly, compounds 4b—4j were
synthesized by using various esters 3b—3j.
1-(10-Acetyl-10H-3-hydroxyphenothiazin-2-yl)-3-
phenylpropane-1,3-dione (4a) Yield 90%, m.p. 216
2,10-Diacetyl-3-benzoyloxyphenothiazine
(3a)
1
Yield 89%, m.p. 134—136 ℃; H NMR (CDCl3) δ:
8.18—6.78 (m, 11H, Ar-H), 2.53 (s, 3H, COCH3), 2.11
(s, 3H, COCH3); IR (KBr) ν: 1676, 1724, 1735 (C＝O),
2866, 2933 (CH2), 3068 (Ar-H); MS m/z (%): 403 [M＋]
(75), 360 (100), 255 (80). Anal. calcd for C23H17NO4S:
C 68.47, H 4.25, N 3.47; found C 68.33, H 4.12, N 3.59.
2,10-Diacetyl-3-(2-chlorobenzoyloxy)phenothia-
1
—218 ℃; H NMR (CDCl3) δ: 7.78—6.68 (m, 11H,
Ar-H), 5.13 (s, 1H, OH), 3.81 (s, 2H, CH2), 2.10 (s, 3H,
COCH3); 13C NMR (CDCl3 ) δ: 22.0 (CH3), 52.3 (CH2),
117.0, 118.3, 118.8, 122.9, 128.9, 129.3, 132.5, 133.1,
134.0, 135.1, 135.8, 136.6, 136.9 (Ar-C), 170.1, 197.6
(C＝O); IR (KBr) ν: 1616, 1690 (C＝O),＋2868, 2923
(CH2), 3065 (Ar-H); MS m/z (%): 403 [M ] (85), 360
(100), 359 (70). Anal. calcd for C23H17NO4S: C 68.47,
H 4.25, N 3.47; found C 68.34, H 4.13, N 3.58.
1
zine (3b) Yield 91%, m.p. 164—165 ℃; H NMR
(CDCl3) δ: 8.10—6.89 (m, 10H, Ar-H), 2.52 (s, 3H,
COCH3), 2.10 (s, 3H, COCH3); IR (KBr) ν: 1674, 1725,
1734 (C＝O), 2867, 2932 (CH2), 3064 (Ar-H); MS m/z
(%): 437 [M＋] (80), 394 (100), 255 (74). Anal. calcd for
C23H16ClNO4S: C 63.08, H 3.68, N 3.20; found C 63.23,
H, 3.52, N 3.09.
1-(10-Acetyl-10H-3-hydroxyphenothiazin-2-yl)-3-
(2-chlorophenyl)propane-1,3-dione (4b) Yield 84%,
m.p. 170—172 ℃; 1H NMR (CDCl3) δ: 7.80—6.89 (m,
10H, Ar-H), 5.12 (s, 1H, OH), 3.80 (s, 2H, CH2), 2.08 (s,
1918
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Chin. J. Chem. 2011, 29, 1917— 1921

Synthesis of New 2-Phenylpyrano[3,2-b]phenothiazin-4(6H)-one Derivatives
3H, COCH3); 13C NMR (CDCl3 ) δ: 22.1 (CH3), 51.7
(CH2), 117.8, 118.6, 118.9, 122.8, 128.6, 128.9, 132.2,
133.1, 133.7, 135.3, 136.1, 136.9, 137.5 (Ar-C) , 170.3,
197.9 (C＝O); IR (KBr) ν: 1614, 1692 (C＝O), 2869,
2930 (CH2), 3060 (Ar-H); MS m/z (%): 437 [M＋] (80),
394 (100), 393 (72). Anal. calcd for C23H16ClNO4S: C
63.08, H 3.68, N 3.20; found C 63.26, H 3.56, N 3.29.
1-(10-Acetyl-10H-3-hydroxyphenothiazin-2-yl)-3-
(3-chlorophenyl)propane-1,3-dione (4c) Yield 78%,
m.p. 260—262 ℃; 1H NMR (CDCl3) δ: 7.84—6.91 (m,
10H, Ar-H), 5.15 (s, 1H, OH), 3.79 (s, 2H, CH2), 2.10 (s,
3H, COCH3); 13C NMR (CDCl3) δ: 22.5 (CH3), 52.0
(CH2), 116.8, 118.1, 118.3, 122.5, 128.1, 129.0, 132.2,
132.3, 133.1, 133.4, 135.4, 136.0, 136.9 (Ar-C), 170.6,
198.0 (C＝O); IR (KBr) ν: 1613, 1694 (C＝O), 2868,
2933 (CH2), 3063 (Ar-H); MS m/z (%): 437 [M＋] (84),
394 (100), 393 (72). Anal. calcd for C23H16ClNO4S: C
63.08, H 3.68, N 3.20; found C 63.21, H 3.54, N 3.30.
1-(10-Acetyl-10H-3-hydroxyphenothiazin-2-yl)-3-
(4-chlorophenyl)propane-1,3-dione (4d) Yield 75%,
m.p. 250—252 ℃; 1H NMR (CDCl3) δ: 7.88—6.75 (m,
10H, Ar-H), 5.12 (s, 1H, OH), 3.80 (s, 2H, CH2), 2.10 (s,
3H, COCH3); 13C NMR (CDCl3) δ: 22.0 (CH3), 52.4
(CH2), 116.9, 118.3, 118.7, 122.6, 128.3, 129.3, 132.4,
133.8, 135.4, 136.0, 136.9 (Ar-C) , 170.3, 197.6 (C＝O);
IR (KBr) ν: 1617, 1699 (C＝O), 2871, 2932 (CH2),
3065 (Ar-H); MS m/z (%): 437 [M＋] (88), 394 (100),
393 (70). Anal. calcd for C23H16ClNO4S: C 63.08, H
3.68, N 3.20; found C 63.20, H 3.56, N 3.29.
1-(10-Acetyl-10H-3-hydroxyphenothiazin-2-yl)-3-
(2-methylphenyl)propane-1,3-dione (4e) Yield 79%,
m.p. 161—163 ℃; 1H NMR (CDCl3) δ: 7.75—6.68 (m,
10H, Ar-H), 5.11 (s, 1H, OH), 3.81 (s, 2H, CH2), 2.42 (s,
3H, COCH3), 2.08 (s, 3H, CH3); 13C NMR (CDCl3 ) δ:
18.3, 22.9 (CH3), 53.1 (CH2), 118.0, 118.7, 119.0, 122.9,
128.5, 129.6, 132.6, 133.9, 136.0, 136.8, 138.0 (Ar-C) ,
170.1, 197.0 (C＝O); IR (KBr) ν: 1616, 1693 (C＝O),
2866, 2930 (CH2), 3063 (Ar-H); MS m/z (%): 417 [M＋]
(80), 374 (100), 373 (73). Anal. calcd for C24H19NO4S:
C 69.05, H 4.59, N 3.36; found C 69.16, H 4.47, N 3.18.
1-(10-Acetyl-10H-3-hydroxyphenothiazin-2-yl)-3-
reaction mixture was kept at room temperature for 1 h.
After cooling the reaction mixture, the solid obtained was
filtered, washed with water and recrystallized from aque-
ous acetic acid to give 5a. Similarly, compounds 5b—5j
were synthesized by using various 1,3-diones 4b—4j.
2-Phenylpyrano[3,2-b]phenothiazin-4(6H)-one (5a)
1
Yield 85%, m.p. 296—298 ℃; H NMR (CDCl3) δ:
8.23 (s, 1H, NH), 7.38—6.68 (m, 12H, Ar-H); 13C NMR
(CDCl3 ) δ: 108.0, 166.2 (pyrano ring-C), 118.7, 119.3,
120.6, 124.1, 126.4, 128.6, 130.6, 134.1, 136.0, 143.9
(Ar-C), 184.3 (C＝O); IR (KBr) ν: 1360 (C—O—C),
1602 (C＝C), 1635 (C＝O), 3065 (Ar-H), 3334 (N—H);
MS m/z (%): 343 [M＋] (100), 342 (80). Anal. calcd for
C21H13NO2S: C 73.45, H 3.82, N 4.08; found C 73.58,
H 3.75, N 4.16.
2-(2-Chlorophenyl)pyrano[3,2-b]phenothiazin-
1
4(6H)-one (5b) Yield 86%, m.p. 286—287 ℃; H
NMR (CDCl3) δ: 8.21 (s, 1H, NH), 7.38—6.58 (m, 11H,
Ar-H); 13C NMR (CDCl3) δ: 106.8, 165.4 (pyrano
ring-C), 118.9, 119.8, 123.8, 125.1, 129.6, 132.6, 134.5,
138.6, 145.8 (Ar-C), 184.0 (C＝O); IR (KBr) ν: 1355
(C—O—C), 1600 (C＝C), 1633 (C＝O), 3062 (Ar-H),
3337 (N—H); MS m/z (%): 377 [M＋] (100), 375 (80).
Anal. calcd for C21H12ClNO2S: C 66.75, H 3.20, N 3.71;
found C 66.68, H 3.05, N 3.86.
2-(3-Chlorophenyl)pyrano[3,2-b]phenothiazin-
1
4(6H)-one (5c) Yield 83%, m.p. 296—297 ℃; H
NMR (CDCl3) δ: 8.22 (s, 1H, NH), 7.39—6.56 (m, 11H,
Ar-H); 13C NMR (CDCl3) δ: 105.9, 165.8 (pyrano
ring-C), 118.9, 120.1, 122.8, 125.4, 129.0, 131.3, 136.4,
138.0, 145.5, 148.0 (Ar-C), 184.6 (C＝O); IR (KBr) ν:
1358 (C—O—C), 1605 (C＝C), 1636 (C＝O), 3064
(Ar-H), 3338 (N—H); MS m/z (%): 377 [M＋] (100),
375 (84). Anal. calcd for C21H12ClNO2S: C 66.75, H
3.20, N 3.71; found C 66.64, H 3.03, N 3.83.
2-(4-Chlorophenyl)pyrano[3,2-b]phenothiazin-
1
4(6H)-one (5d) Yield 88%, m.p. 314—316 ℃; H
NMR (CDCl3) δ: 8.19 (s, 1H, NH), 7.31—6.59 (m, 11H,
Ar-H); 13C NMR (CDCl3) δ: 106.0, 165.9 (pyrano
ring-C), 119.2, 120.6, 122.9, 125.6, 129.2, 132.3, 133.0,
137.3, 145.5, 148.0 (Ar-C), 184.9 (C＝O); IR (KBr) ν:
1356 (C—O—C), 1603 (C＝C), 1637 (C＝O), 3062
(Ar-H), 3339 (N—H); MS m/z (%): 377 [M＋] (100),
375 (86). Anal. calcd for C21H12ClNO2S: C 66.75, H
3.20, N 3.71; found C 66.62, H 3.11, N 3.86.
(4-methoxyphenyl)propane-1,3-dione (4j)
Yield
1
87%, m.p. 204—206 ℃; H NMR (CDCl3) δ: 7.72—
6.79 (m, 10H, Ar-H), 5.18 (s, 1H, OH), 3.81 (s, 2H,
CH2), 3.73 (s, 3H, COCH3), 2.08 (s, 3H); 13C NMR
(CDCl3 ) δ: 22.1 (CH3), 52.8 (CH2), 60.2 (OCH3), 118.0,
118.7, 119.0, 122.9, 128.5, 129.6, 132.6, 133.9, 136.0,
136.8, 138.0 (Ar-C), 170.3, 197.6 (C＝O); IR (KBr) ν:
1616, 1692 (C＝O), 2867, 2931 (CH2), 3062 (Ar-H);
MS m/z (%): 433 [M＋] (82), 390 (100), 389 (76). Anal.
calcd for C24H19NO5S: C 66.50, H 4.42, N 3.23; found
C 66.34, H 4.34, N 3.16.
2-(2-Methylphenyl)pyrano[3,2-b]phenothiazin-
1
4(6H)-one (5e) Yield 85%, m.p. 236—238 ℃; H
NMR (CDCl3) δ: 8.18 (s, 1H, NH), 7.21—6.56 (m, 11H,
Ar-H), 2.38 (s, 3H); 13C NMR (CDCl3) δ: 19.6 (CH3),
105.6, 165.4 (pyrano ring-C); 119.0, 120.2, 122.5, 125.8,
128.6, 130.2, 133.0, 137.8, 145.0, 147.8 (Ar-C), 184.5
(C＝O); IR (KBr) ν: 1355 (C—O—C), 1604 (C＝C),
1634 (C＝O), 2980 (C—H), 3063 (Ar-H), 3337 (N—H);
MS m/z (%): 357 [M＋] (100), 356 (82). Anal. calcd for
C22H15NO2S: C 73.93, H 4.23, N 3.92; found C 73.82,
H 4.31, N 3.78.
General procedure for synthesis of pyranopheno-
thiazines 5a— 5j
1-(10-Acetyl-3-hydroxy-10H-phenothiazin-2-yl)-3-
phenylpropane-1,3-dione (4a) (0.05 mmol) was refluxed
in acetic acid-HCl mixture (5 mL) for 30 min. Then the
2-(4-Methoxyphenyl)pyrano[3,2-b]phenothiazin-
1
4(6H)-one (5j) Yield 88%, m.p. 317—318 ℃; H
Chin. J. Chem. 2011, 29, 1917— 1921
© 2011 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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1919

Bansode & Meshram
FULL PAPER
NMR (CDCl3) δ: 8.18 (s, 1H, NH), 7.18—6.59 (m, 11H,
Ar-H), 3.72 (s, 3H, OCH3); 13C NMR (CDCl3) δ: 59.6
(OCH3), 105.6, 166.3 (pyrano ring-C), 119.0, 120.2,
124.5, 125.0, 126.9, 131.4, 135.0, 139.8, 146.0, 148.2,
157.8 (Ar-C), 184.9 (C＝O); IR (KBr) ν: 1359 (C—O—
C), 1606 (C＝C), 1638 (C＝O), 3060 (Ar-H), 3338
(N—H); MS m/z (%): 373 [M＋] (100), 372 (78). Anal.
calcd for C22H15NO3S: C 70.76, H 4.05, N 3.75; found
C 70.59, H 3.89, N 3.88.
rum. The IR spectra of compound 5a showed charac-
－1
teristic absorptions at 1360 cm
due to C—O—C
－1
－1
stretch, 1602 cm due to C＝C stretch, 3065 cm due
－1
1
to Ar-H and 3334 cm due to N—H stretch. The H
NMR spectrum of 5a showed a singlet at δ 8.23 due to
N-H proton. It showed multiplets at δ 7.38—6.68 due to
aromatic protons. The 13C NMR spectrum of 5a showed
two peaks at δ 108.0, 166.2 for pyrano ring carbons, ten
peaks at δ 118.7, 119.3, 120.6, 124.1, 126.4, 128.6,
130.6, 134.1, 136.0, 143.9 for aromatic carbons and one
peak at δ 184.3 for carbonyl carbon. Further evidence
for the formation of compound 5a was obtained by re-
cording the mass spectra. The mass spectrum of com-
pound 5a showed a molecular ion peak at m/z 343
which is in conformity with the molecular formula
C21H13NO2S.
Results and discussion
Compound 2 was obtained by Friedel Crafts acyla-
tion and simultaneous demethylation of 10-acetyl
3-methoxy phenothiazine 1. The further esterification of
2,10-diacetyl-3-hydroxy phenothiazine 2 with various
substituted benzoic acid in the presence of phosphorous
oxychloride in pyridine at room temperature gave 3a—
3j. Compounds 3a—3j were converted into 1,3-diones
4a—4j by Baker-Venkataraman method, i.e. 2,10-di-
acetyl-3-aryoyloxy phenothiazines 3a—3j were treated
with powdered KOH in dry pyridine for 1 h. The
1,3-diones thus obtained were cyclised to pyronopheno-
thiazines (5a—5j) by refluxing in an acetic acid/HCl
mixture (Scheme 1).
Conclusions
In conclusion, we have developed a simple and effi-
cient method for the synthesis of pyranophenothiazine
derivatives. We also believe that the procedural simplic-
ity and efficiency give easy accessibility to the reaction.
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