An efficient synthesis of 1,5-thiadiazepines and 1,5-benzodiazepines by microwave-assisted heterocyclization

Article abstract of DOI:10.1080/10426500600864775

A novel and efficient method for the synthesis of substituted thiazepines and diazepines has been developed. A simple one-pot reaction of chalcones 1a-f with 1-amino-2-mercapto-5-phenyl-1,3,4-triazole and o-phenylenediamine in the presence of a catalytic

Full text of DOI:10.1080/10426500600864775

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An Efficient Synthesis
of 1,5-Thiadiazepines
and 1,5-Benzodiazepines
by Microwave-Assisted
Heterocyclization
Gundibasappa K. Nagaraja a , Vijayavittala P. Vaidya
b , Koodamara Sheshappa Rai a & Kittappa M.
Mahadevan b
a Department of PG Studies and Research in Polymer
Science , University of Mysore, Sir M. V. PG Centre,
Thubinakere , Mandya, Karnataka, India
b Department of PG Studies and Research in
Chemistry , Kuvempu University, Shankaraghatta ,
Shimoga, Karnataka, India
Published online: 22 Nov 2006.
To cite this article: Gundibasappa K. Nagaraja , Vijayavittala P. Vaidya , Koodamara
Sheshappa Rai & Kittappa M. Mahadevan (2006) An Efficient Synthesis of 1,5-
Thiadiazepines and 1,5-Benzodiazepines by Microwave-Assisted Heterocyclization,
Phosphorus, Sulfur, and Silicon and the Related Elements, 181:12, 2797-2806, DOI:
10.1080/10426500600864775
To link to this article: http://dx.doi.org/10.1080/10426500600864775
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Phosphorus, Sulfur, and Silicon, 181:2797–2806, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600864775
An Efficient Synthesis of 1,5-Thiadiazepines and
1,5-Benzodiazepines by Microwave-Assisted
Heterocyclization
Gundibasappa K. Nagaraja
Department of PG Studies and Research in Polymer Science, University
of Mysore, Sir M. V. PG Centre, Thubinakere, Mandya, Karnataka, India
Vijayavittala P. Vaidya
Department of PG Studies and Research in Chemistry, Kuvempu
University, Shankaraghatta, Shimoga, Karnataka, India
Koodamara Sheshappa Rai
Department of PG Studies and Research in Polymer Science, University
of Mysore, Sir M. V. PG Centre, Thubinakere, Mandya, Karnataka, India
Kittappa M. Mahadevan
Department of PG Studies and Research in Chemistry, Kuvempu
University, Shankaraghatta, Shimoga, Karnataka, India
A novel and efficient method for the synthesis of substituted thiazepines and
diazepines has been developed. A simple one-pot reaction of chalcones 1a–f
with 1-amino-2-mercapto-5-phenyl-1,3,4-triazole and o-phenylenediamine in the
presence of a catalytic amount of sodium acetate under microwave irradi-
ation gave 2-(3,8-diphenyl-7,8-dihydro[1,2,4]triazolo[3,4-b][1,3,4]thiadiazepin-6-
yl)phenoles 2a–f and 2-(2-phenyl-2,3-dihydro-1H-1,5-benzodiazepin-4-yl)phenoles
3a–f, respectively. The structure of all the synthesized compounds was elucidated
on the basis of elemental analysis, IR, 1H and 13C NMR, and mass spectral data.
Keywords 1-amino-2-mercapto-5-aryl-1,3,4-triazole; chalcones; heterocycliczation;
microwave irradiation; o-phenylenediamine
Received; accepted.
The authors are thankful to the Professor and Chairman, Kuvempu University,
Shankaraghatta, for providing research facilities and the head of the Sophisticated
Instruments Facility, IISc, Bangalore, for spectral data.
Address correspondence to Kittappa M. Mahadevan, Kuvempu University, Depart-
ment of PG Studies and Research in Chemistry, Shankaraghatta, Shimoga, Karnataka,
577 451 India. E-mail: mady kmm@yahoo.co.uk
2797

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G. K. Nagaraja et al.
INTRODUCTION
The synthesis of compounds belonging to the thiazepine and diazepine
series constitute an important area of research due to their interest-
ing diverse biological activities, such as antibacterial,1 antifeedent,2
analgesic,3 anticoagulant,4 antihypertensive,5 and antidepresent6
properties. In addition, 1,5-benzothiazepines and benzodiazepines are
used as starting materials for the preparation of fused ring compounds,
such as triazolo- and oxadiazolo-benzodiazepines.7 Despite their impor-
tance from a pharmacological and synthetic point of view, few methods
for the preparation of benzodiazepines and benzothiazepines are re-
ported in the literature.8–10 Recently, Dandia et al. reported a solvent-
free synthesis of 1,5-benzothiazepines in the presence of a solid support
under microwave irradiation.11 The most straightforward protocol for
the synthesis of 1,5- benzothiazepines 2a–f and benzodiazepines 3a–f
involves the one-pot condensation of chalcones 1a–f with 1-amino-
2-mercapto-5-aryl-1,3,4-triazoles and o-phenylenediamine in ethanol
under strongly acidic conditions.12–13 However, the combination of
solvents, a strong acid, and long reaction time makes this method envi-
ronmentally hazardous. Thus, a simple, general, and efficient procedure
for the synthesis of this important heterocyclic system is required. Re-
cently, Microwave-Induced Organic Reaction Enhancement (MORE)
chemistry is gaining popularity as an unconventional technique for
rapid organic synthesis.14–15 Many researchers have described accel-
erated organic reactions, and a number of papers appeared proving the
synthetic utility of MORE chemistry in routine organic synthesis.16–17
In continuation of our work on the synthesis of novel heterocyclic
compounds18–21 under the framework of “green chemistry,” we report
herein the synthesis of 1,5-benzodiazepines and benzothiazepines by
the reaction of chalcones with o-phenylenediamine and 1-amino-2-
mercapto-5-phenyl-1,3,4-triazole in the presence of sodium acetate in
DMSO as an environmentally benign synthesis of the title compounds.
A further advantage of this method is the synthesis on a preparative
scale in one step.
The starting compounds 1a–f required for the study were prepared
by the reaction of 2-hydroxyacetophenone with various benzaldehydes
according to the reported method.22 Chalcones 1a–f, when reacted with
1-amino-2-mercapto-5-phenyl-1,3,4-triazole in the presence of sodium
acetate in DMSO, underwent heterocyclization to give the correspond-
ing 1,5-thiadiazepines 2a–f (Scheme 1) in good yields.
Similarly, the synthesis of 1,5-diazepines 3a–f (Scheme 2) was
accomplished by employing the reaction of chalcones with o-
phenylenediamine followed by heterocyclization under microwave

1,5-Thiadiazepines and 1,5-Benzodiazepines
2799
SCHEME 1
irradiation in excellent yields of 78–95%. This new approach firmly
confirms the great utility of microwave stimulation in heterocycliza-
tion reactions for the synthesis of complex condensed heterocyclic
systems.
SCHEME 2

2800
G. K. Nagaraja et al.
RESULTS AND DISCUSSION
The formation of the products probably involves the intermediates 4
or 5, (Scheme 3) which could produce 2a–f and 3a–f. The formation of
the condensed heterocyclic compounds by the dehydration of 4 could
be favorable in a nonaqueous medium. A dipolar transition state is
involved in the formation of intermediates 4 and 5 by the 1,2- and
1,4-addition23 to the carbonyl group and to the β-carbon atom of the
α, β-unsaturated carbonyl system, followed by cyclization to give title
compounds.
SCHEME 3
Many of the conventional methods for heterocyclization with chal-
cones need strong basic conditions and give enamines, which tautomer-
ize to diazepines. In this case, cyclization occurred under a microwave
irradiation condition even in the presence of the weak base sodium ac-
etate. Microwave-assisted synthesis yielded the tautomerized ring sys-
1
tem as indicated by H NMR studies. Structures of synthesized com-
pounds were assigned on the basis of their IR, 1H NMR, and mass
spectral data. The IR spectrum of 1a showed an absorption band at
1640 cm−1 corresponding to the carbonyl group. 1-amino-2-mercapto-5-
phenyl-1,3,4-triazole displayed peaks at 3410–2580 cm−1 correspond-
ing to NH and SH, which were found to be absent in the IR spectrum
of 2a. Also, 2a showed the absence of a band at 1650–1653 cm−1 corre-
sponding to a carbonyl group, thus further confirming the ring closure.
The 1H NMR spectrum of 2a recorded in DMSO as a solvent showed
signals only in the aromatic region corresponding to 16 protons, of which
14 were attributed to aromatic protons (δ = 6.86–8.18), one to NH
(δ = 8.09), and another to CH = (δ = 7.83) of the azepine ring. The
>CH S proton was found to resonate at δ = 3.40 ppm. The structure
assigned was further confirmed by mass spectral studies. It gave the

1,5-Thiadiazepines and 1,5-Benzodiazepines
2801
molecular ion peak at m/z 398 (M+), 305, 298, 279, 253 (100%), 224,
197, 165, 121, 105, 89, and 77, and compound 3a gave m/z 312 (M+),
235, 209 (100%), 182, 133, 119, 91, and 65.
To conclude, the present investigation describes a two-step synthe-
sis of the heterocycles 2 and 3. The microwave-assisted route, besides
being advantageous because of the simple reaction conditions and the
easy work-up procedures, has resulted in improved yields compared to
conventional methods.
EXPERIMENTAL
All reagents were obtained commercially and used without further pu-
rification. Melting points were determined on a Koflar hot-stage appa-
ratus and are uncorrected. IR spectra were recorded with a FT Bruker
1
spectrometer in KBr pellets. H and 13C NMR spectra were recorded
with a Varian VXR-300 (300 MHz) spectrometer in DMSO-d6 solutions.
Chemical shifts are given in ppm downfield from TMS. Microanalyses
were obtained with a fisions EA 1108 instrument. Silica gel (Merck;
60–120 mesh) and DC-Alufolien 60 F254 were normally used for col-
umn and thin layer chromatography, respectively. Microwave-assisted
procedures were carried out in a domestic Whirlpool microwave oven
operating at 1000 W.
The Synthesis of 1,5-Thiazepines 2a–f: General Procedure
Equimolar quantities of 1-amino-2-mercapto-5-phenyl-1,3,4-triazole
(0.96 g, 5 mmol) and chalcone (1.12 g, 5 mmol) in 15 mL of DMSO
containing a catalytic amount of sodium acetate were filled in a conical
flask capped with a glass funnel, placed in a microwave oven, and irra-
diated for 6–8 min at 500 W with short interruptions of 30 sec to 1 min
to avoid an excessive evaporation of the solvent. The progress of the
reaction was monitored by TLC. The reaction mixture was cooled to r.t.,
diluted with water (2 × 50 mL), and extracted with CHCl3(2 × 25 mL).
The solvent was evaporated, and the residue recrystallized from ethanol
to afford analytically pure samples of 2a–f.
2-(3,8-Diphenyl-7,8-dihydro[1,2,4]triazolo[3,4-
b][1,3,4]thiadiazepin-6-yl)phenol (2a)
Solid; (83%), m.p. 180–183◦C, MS: (M+) 398; IR (KBr, ν, cm−1): 1320
1
(C N), 1595 (C C), 1689 (C N); H NMR (δ, DMSO-d6): 3.41 (d, 1H,
CH S), 6.85–8.21 (m, 14H, Ar H), 7.84 (s, 1H, CH ), 8.05 (s, 1H,
NH), 10.29 (s, 1H, OH); 13C NMR (δ, DMSO-d6): 145.1 (C OH),

2802
G. K. Nagaraja et al.
112.1, 113.2, 114.4, 115.3, 116.4, 126.1, 126.3, 127.2, 127.4, 128.3, 128.5,
130.1, 131.3, 132.2, 132.1, 133.2, 133.5, 134.1, 134.8 (aromatic carbons),
164.1 (C4, C N), 166.3 (C10, C N), 167.4 (C7, C N); anal. calcd. for
C23N4OH18S (398.48): C, 69.32; H, 4.55; N, 14.06. Found: C, 69.10; H,
4.50; N, 13.95.
2-[8-(4-Nitrophenyl)-3-phenyl-7,8-dihydro[1,2,4]triazolo[3,4-
b][1,3,4]thiadiazepin-6-yl)phenol (2b)
Solid; (92%), m.p. 192–195◦C, MS: (M+) 443; IR (KBr, ν, cm−1): 1325
1
(C N), 1350 (N O), 1625 (C C), 1689 (C N); H NMR (δ, DMSO-d6):
3.40 (d, 1H, CH S), 6.84–8.20 (m, 13H, Ar H), 7.81 (s, 1H, CH ),
8.15 (s, 1H, NH), 10.28 (s, 1H, OH); 13C NMR (δ, DMSO-d6): 121.2
(C NO2), 145.13 (C OH), 112.2, 113.2, 114.4, 115.3, 116.4, 126.2, 126.2,
127.4, 128.3, 128.4, 130.1, 131.3, 132.2, 132.2, 133.1, 133.4, 134.2,
134.8 (aromatic carbons), 164.2 (C4, C N), 166.2 (C10, C N), 167.4
(C7, C N); anal. calcd. for C23N5O3H17S (443.48): C, 62.29; H, 3.86; N,
15.79. Found: C, 61.85; H, 3.90; N, 15.65.
2-[8-(4-Chlorophenyl)-3-phenyl-7,8-dihydro[1,2,4]triazolo[3,4-
b][1,3,4]thiadiazepin-6-yl)phenol (2c)
Solid; (87%), m.p. 187–190◦C, MS: (M+) 432; IR (KBr, ν, cm−1): 1315
1
(C N), 1615 (C C), 1679 (C N); H NMR (δ, DMSO-d6): 3.42 (d, 1H,
CH S), 6.86–8.19 (m, 13H, Ar H), 7.83 (s, 1H, CH ), 8.09 (s, 1H,
NH), 10.30 (s, 1H, OH); 13C NMR (δ, DMSO-d6): 134.6 (C Cl), 145.7
(C OH), 112.2, 113.2, 114.3, 115.3, 116.4, 126.2, 126.3, 127.2, 128.2,
128.5, 130.1, 131.4, 132.2, 132.1, 133.1, 133.4, 134.2, 134.8 (aromatic
carbons), 164.1 (C4, C N), 166.3 (C10, C N), 167.4 (C7, C N); anal.
calcd. for C23N4OH17SCl (432.93): C, 63.81; H, 3.96; N, 12.94. Found: C,
63.45; H, 3.60; N, 11.95.
2-[8-(4-Hydroxyphenyl)-3-phenyl-7,8-dihydro[1,2,4]triazolo-
[3,4-b][1,3,4]thiadiazepin-6-yl)phenol (2d)
Solid; (90%), m.p. 195–197◦C, MS: (M+) 414; IR (KBr, ν, cm−1): 1325
(C N), 1645 (C C), 1680 (C N), 3325 (O H, H-bonding), 3594 (O H);
1H NMR (δ, DMSO-d6): 3.40 (d, 1H, CH S), 6.87–8.21 (m, 13H, Ar H),
7.86 (s, 1H, CH ), 8.10 (s, 1H, NH), 9.81 (s, 1H, OH), 10.29 (s, 1H,
OH); 13C NMR (δ, DMSO-d6): 145.5 (C OH), 112.4, 113.2, 114.4, 115.4,
116.4, 126.17, 126.22, 127.2, 128.2, 128.5, 130.2, 131.4, 132.13, 132.15,
133.2, 133.5, 134.1, 134.8 (aromatic carbons), 164.1 (C4, C N), 166.3

1,5-Thiadiazepines and 1,5-Benzodiazepines
2803
(C10, C N), 167.5 (C7, C N); anal. calcd. for C23N4O2H18S (414.98):
C, 66.65; H, 4.38; N, 13.52. Found: C, 65.95; H, 4.10; N, 13.50.
2-[8-(4-Methoxyphenyl)-3-phenyl-7,8-dihydro[1,2,4]triazolo-
[3,4-b][1,3,4]thiadiazepin-6-yl)phenol (2e)
Solid; (84%), m.p. 183–185◦C, MS: (M+) 428; IR (KBr, ν, cm−1): 1260
(O C), 1340 (C N), 1669 (C N), 1675 (C C); 1H NMR (δ, DMSO-
d6): 3.42 (d, 1H, CH S), 3.82 (s, 3H, OCH3), 6.83–8.17 (m, 13H,
Ar H), 7.87 (s, 1H, CH ), 8.03 (s, 1H, NH), 10.31 (s, 1H, OH);
13C NMR (δ, DMSO-d6): 56.2 (OCH3), 145.6 (C OH), 159.4 (C OCH3),
112.6, 113.2, 114.2, 115.3, 116.4, 126.2, 126.3, 127.2, 128.2, 128.5,
130.1, 131.4, 132.2, 132.1, 133.1, 133.4, 134.2, 134.8 (aromatic carbons),
164.1 (C4, C N), 166.3 (C10, C N), 167.5 (C7, C N); anal. calcd. for
C24N4O2H20S (428.51): C, 67.27; H, 4.70; N, 13.07. Found: C, 67.10; H,
4.97; N, 13.45.
2-[8-(4-Methylphenyl)-3-phenyl-7,8-dihydro[1,2,4]triazolo[3,4-
b][1,3,4]thiadiazepin-6-yl]phenol (2f)
Solid; (80%), m.p. 180–184◦C, MS: (M+) 412; IR (KBr, ν, cm−1): 1340
1
(C N), 1635 (C C), 1675 (C N); H NMR (δ, DMSO-d6): 3.15 (s, 3H,
CH3), 3.41 (d, 1H, CH S), 6.86–8.20 (m, 13H, Ar H), 7.89 (s, 1H,
CH ), 8.05 (s, 1H, NH), 10.30 (s, 1H, OH); 13C NMR (δ, DMSO-d6):
36.2 (CH3), 136.2 (C CH3), 145.3 (C OH), 112.3, 113.2, 114.5, 115.3,
116.4, 126.15, 126.24, 127.4, 128.3, 128.4, 130.1, 131.3, 132.17, 132.15,
133.1, 133.4, 134.2, 134.8 (aromatic carbons); 164.1 (C4, C N), 166.3
(C10, C N), 167.4 (C7, C N); anal. calcd. for C24N4OH20S (412.51): C,
69.88; H, 4.89; N, 13.58. Found: C, 69.75; H, 4.25; N, 12.90.
The Synthesis of 1,5-Diazepines 3a–f: General Procedure
The same procedure that was previously described was followed with
equimolar quantities of o-phenylenediamine (0.54 g, 5 mmol) and chal-
cone (1.12 g, 5 mmol) in 15 mL of DMSO containing a catalytic amount
of sodium acetate.
2-(2-Phenyl-2,3-dihydro-1H-1,5-benzodiazepin-4-yl)phenol (3a)
Solid; (86%), m.p. 108–110◦C, MS: (M+) 312; IR (KBr, ν, cm−1): 1320
1
(C N), 1595 (C C), 1689 (C N), 3300 (O H), 3340 (N H); H NMR
(δ, DMSO-d6): 6.87–8.21 (m, 13H, Ar H), 7.86 (s, 1H, CH ), 8.06 (s,
1H, NH), 10.29 (s, 1H, OH); 13C NMR (δ, DMSO-d6): 145.6 (C OH),

2804
G. K. Nagaraja et al.
112.4, 113.3, 114.1, 114.4, 115.6, 116.6, 126.2, 126.6, 127.4, 128.3, 128.6,
130.1, 131.2, 132.1, 132.5, 133.5, 133.6, 134.2, 134.6, (aromatic carbons),
165.8 (C N); anal. calcd. for C21H16N2O (312.36): C, 80.75; H, 5.16; N,
8.97. Found: C, 80.60; H, 5.05; N, 8.86.
2-[2-(4-Nitrophenyl)-2,3-dihydro-1H-1,5-benzodiazepin-4-
yl]phenol (3b)
Solid; (95%), m.p. 123–125◦C, MS: (M+) 357; IR (KBr, ν, cm−1): 1325
(C N), 1350 (N O), 1625 (C C), 1690 (C N), 3310 (O H), 3345 (N H);
1H NMR (δ, DMSO-d6): 6.86–8.20 (m, 12H, Ar H), 7.82 (s, 1H, CH ),
8.07 (s, 1H, NH), 10.30 (s, 1H, OH); 13C NMR (δ, DMSO-d6): 145.3
(C OH), 121.2 (C NO2), 112.4, 113.3, 114.2, 114.3, 115.6, 116.6, 126.2,
126.6, 128.3, 128.6, 130.1, 131.2, 132.1, 132.4, 133.4, 133.7, 134.1, 134.5,
(aromatic carbons), 165.7 (C N); anal. calcd. for C21H15N3O3 (357.36):
C, 70.58; H, 4.23; N, 11.76. Found: C, 70.51; H, 4.25; N, 11.75.
2-[2-(4-Chlorophenyl)-2,3-dihydro-1H-1,5-benzodiazepin-4-
yl]phenol (3c)
Solid; (85%), m.p. 117–120◦C, MS: (M+) 346; IR (KBr, ν, cm−1): 1320
1
(C N), 1630 (C C), 1635 (C N), 3325 (O H), 3345 (N H); H NMR
(δ, DMSO-d6): 6.83–8.17 (m, 12H, Ar H), 7.78 (s, 1H, CH ), 8.09 (s,
1H, NH), 10.28 (s, 1H, OH); 13C NMR (δ, DMSO-d6): 134.6 (C Cl),
145.4 (C OH), 112.5, 113.3, 114.1, 114.3, 115.5, 116.6, 126.2, 126.6,
127.4, 128.3, 128.6, 130.1, 131.2, 132.1, 132.5, 133.3, 133.7, 134.2, 134.5,
(aromatic carbons), 164.2 (C N); anal. calcd. for C21N2OH15Cl (346.81):
C, 72.73; H, 4.36; N, 8.08. Found: C, 72.90; H, 4.59; N, 8.05.
2-[2-(4-Hydroxyphenyl)-2,3-dihydro-1H-1,5-benzodiazepin-4-
yl]phenol (3d)
Solid; (91%), m.p. 110–115◦C, MS: (M+) 328; IR (KBr, ν, cm−1): 1335
(C-N), 1589 (C N), 1595 (C C), 3320 (N H), 3345 (O H, H bonding),
1
3684 (O H); H NMR (δ, DMSO-d6): 6.87–8.21 (m, 12H, Ar H), 7.76
(s, 1H, CH ), 8.12 (s, 1H, NH), 9.79 (s, 1H, OH), 10.30 (s, 1H,
OH), 13C NMR (δ, DMSO-d6)δ: 145.5 (C OH), 112.5, 113.4, 114.2,
114.4, 115.5, 116.7, 126.2, 126.6, 127.4, 128.3, 128.6, 130.2, 131.2, 132.2,
132.5, 133.4, 133.7, 134.2, 134.5, (aromatic carbons), 165.1 (C N); anal.
calcd. for C21N2O2H16(328.36): C, 76.81; H, 4.91; N, 8.53. Found: C,
76.20; H, 5.20; N, 8.45.

1,5-Thiadiazepines and 1,5-Benzodiazepines
2805
2-[2-(4-Methoxyphenyl)-2,3-dihydro-1H-1,5-benzodiazepin-4-
yl]phenol (3e)
Solid; (86%), m.p. 120–122◦C, MS: (M+) 342; IR (KBr, ν, cm−1): 1230
(C O), 1330 (C N), 1625 (C C), 1659 (C N), 3300 (N H), 3335 (O H);
1H NMR (δ, DMSO-d6): 3.75 (s, 3H, OCH3), 6.83–8.17 (m, 12H, Ar H),
7.81 (s, 1H, CH ), 8.06 (s, 1H, NH), 10.28 (s, 1H, OH); 13C NMR
(δ, DMSO-d6): 56.6 (OCH3), 145.3 (C OH), 112.4, 113.3, 114.2, 114.3,
115.6, 116.6, 126.2, 126.6, 128.3, 128.6, 130.1, 131.2, 132.1, 132.4, 133.4,
133.7, 134.1, 134.5, (aromatic carbons), 165.7 (C N); anal. calcd. for
C22N2O2H18 (342.39): C, 77.17; H, 5.30; N, 8.18. Found: C, 77.59; H,
5.25; N, 8.05.
2-[2-(4-Methylphenyl)-2,3-dihydro-1H-1,5-benzodiazepin-4-
yl]phenol (3f)
Solid; (78%), m.p. 125–127◦C, MS: (M+) 326; IR (KBr, ν, cm−1): 1320
(C-N), 1620 (C C), 1689 (C N), 3310 (O H), 3350 (N H); 1H NMR (δ,
DMSO-d6): 3.21 (s, 3H, CH3), 6.86–8.20 (m, 12H, Ar H), 7.82 (s, 1H,
CH ), 8.05 (s, 1H, NH), 10.31 (s, 1H, OH); 13C NMR (δ, DMSO-
d6) δ: 36.2 (CH3), 145.6 (C OH), 112.5, 113.3, 114.1, 114.4, 115.5, 116.7,
126.2, 126.6, 128.3, 128.6, 130.1, 131.2, 132.2, 132.4, 133.4, 133.7, 134.1,
134.5, (aromatic carbons), 166.0 (C N); anal. calcd. for C22N2OH18
(326.39): C, 80.96; H, 5.56; N, 8.58. Found: C, 79.95; H, 6.05; N, 8.49.
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