Intramolecular amidation: Synthesis of novel thiazole-fused diazepinones

Article abstract of DOI:10.1080/00397910600978481

A new class of thiazole-fused diazepinones has been synthesized by the application of intramolecular hydrazonolysis, wherein 2-arylamino-4-coumarinyl- 5-formyl thiazoles were treated with hydrazine hydrate in refluxing ethanol to yield the rearranged prod

Full text of DOI:10.1080/00397910600978481

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Intramolecular Amidation: Synthesis of Novel
Thiazole‐Fused Diazepinones
Rajesh S. Koti a , Gundurao D. Kolavi a , Vinayak S. Hegde a & I. M. Khazi a
a Department of Chemistry , Karnatak University , Dharwad, India
Published online: 25 Jul 2007.
To cite this article: Rajesh S. Koti , Gundurao D. Kolavi , Vinayak S. Hegde & I. M. Khazi (2007)
Intramolecular Amidation: Synthesis of Novel Thiazole‐Fused Diazepinones, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry, 37:1, 99-105, DOI:
10.1080/00397910600978481
To link to this article: http://dx.doi.org/10.1080/00397910600978481
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Synthetic Communicationsw, 37: 99–105, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600978481
Intramolecular Amidation: Synthesis
of Novel Thiazole-Fused Diazepinones
Rajesh S. Koti, Gundurao D. Kolavi, Vinayak S. Hegde,
and I. M. Khazi
Department of Chemistry, Karnatak University, Dharwad, India
Abstract: A new class of thiazole-fused diazepinones has been synthesized by
the application of intramolecular hydrazonolysis, wherein 2-arylamino-4-coumarinyl-
5-formyl thiazoles were treated with hydrazine hydrate in refluxing ethanol to yield
the rearranged products via an interesting ring-opening and cyclization process.
Keywords: diazepinone, intramolecular amidation, thiazole derivatives
INTRODUCTION
Thiazolodiazepinone is a new class of fused-ring system and has not yet been
reported. The general approach for the construction of the diazepinone ring
was by cyclization of properly substituted N-iminopyridinium ylides,[1] diaza-
norcaradiene,[2] and unsaturated ketone N-tosylhydrazones.[3] We report
herein the synthesis of thiazolodiazepinones from a functionalized thiazole
by intramolecular amidation reaction.
RESULTS AND DISCUSSION
The required 2-arylamino-4(30-coumarinyl-5-formyl thiazoles (IVa–g)
were prepared (Scheme 1) by a Vilsmeier–Haack reaction of 2-arylamino-
4-coumarinyl thiazoles (IIIa–g). The reaction of these derivatives (IVa–g)
Received in India May 22, 2006
Address correspondence to I. M. Khazi, Department of Chemistry, Karnatak Uni-
versity, Dharwad 580 003, India. E-mail: drimkorgchem@gmail.com
99

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R. S. Koti et al.
Scheme 1. R ¼ H, 2-Cl, 3-Cl, 4-Cl, 3-NO2, 2-CH3 2-OCH3.
with hydrazine hydrate resulted in the formation of thiazolodiazepinones
(Va–g).
The structures of 2-(2-arylamino)-8-(2-hydroxybenzylidine)6,8-dihydro
7H[1,3]thiazolo[5,4-d][1,2]diazepin-7-ones (Va–g) were established by the
analytical and spectral data. The infrared spectrum of Va–g showed a
strong nO-H band in the region 3345–3339 cm21 along with a nNH band
around 2975–2960 cm21. The absence of nC55O of the coumarin ring around
1710–1700 cm21 and the appearance of nC55O of lactam in the region of
1640–1630 cm21 clearly established the conversion of 2-arylamino-4-cou-
marinyl-5-formyl thiazoles (IVa–g) to 2-(2-arylamino)-8-(2-hydroxybenzyli-
dine)-6,8-dihydro7H[1,3]thiazolo[5,4-d][1,2]diazepin-7-ones (Va–g). Finally,
structures of the compounds (Va–g) were confirmed by 1H NMR, 13C NMR,
and mass spectra.
EXPERIMENTAL
Melting points were determined in open capillaries and are uncorrected. The
IR spectra were recorded on Nicolet Impact 410 FT IR spectrophotometer
1
using KBr pellets. H and 13C NMR were recorded on Bruker 300-MHz FT
NMR spectrometer in CDCl3 and DMSO-d6 with TMS as internal standard.
Mass spectra (MS) were recorded on a EI-70 EV instrument and elemental
analysis was carried out using Heraus CHN rapid analyzer.
Preparation of 2-arylamino-4-coumarinyl thiazoles (IIIa–g);
General Method
A
solution of appropriately substituted thiourea[4–6] (0.1 mol) and
3-bromoacetyl coumarin[7,8] (26.7 g, 0.1 mol) in dry ethanol was refluxed

Thiazole-Fused Diazepinones
101
for 12 h. The solvent was removed under diminished pressure. The crude
product that separated was filtered and basified with aqueous ammonia,
washed with water, dried, and recrystallized from aqueous ethanol.
Data
2-Phenylamino-4-coumarinyl thiazole (IIIa): Brown crystals; mp
140–1428C; yield 56%; IR (KBr) n 3304 (NH), 1705 (C55O) 1557
1
(C55N) cm21; H NMR (DMSO-d6) d 8.58 (s, 1H, coumarinyl C4-H), 8.15
(s, 1H, NH), 7.75 (s, 1H, C5-H), 7.70–7.00 (m, 9H, ArH). Anal. calcd. for
C18H12N2O2S: C, 67.50; H, 3.75; N, 8.75%. Found: C, 67.15; H, 3.66;
N, 8.56%.
2-(2-Chlorophenyl)amino-4-coumarinyl thiazole (IIIb): Pale yellow
crystals; mp 150–1518C; yield 60%; IR (KBr) n 3310 (NH), 1710 (C55O),
1
1550 (C55N) cm21; H NMR (DMSO-d6) d 8.50 (s, 1H, coumarinyl C4-H),
8.20 (s, 1H, NH), 7.65(s, 1H, C5-H), 7.60–7.10 (m, 8H, ArH). Anal. calcd.
for C18H11ClN2O2S: C, 60.93; H, 3.10; N, 7.89%. Found: C, 60.56; H,
3.17; N, 8.20%.
2-(3-Chlorophenyl)amino-4-coumarinyl thiazole (IIIc): Yellow crystals;
mp 134–1358C; yield 58%; IR (KBr) n 3319 (NH), 1706 (C55O) 1548
1
(C55N) cm21; H NMR (DMSO-d6) d 8.60 (s, 1H, coumarinyl C4-H), 8.20
(s, 1H, NH), 8.00(s, 1H, C5-H), 7.90–7.00 (m, 8H, ArH). Anal. calcd. for
C18H11ClN2O2S: C, 60.93; H, 3.10; N, 7.89%. Found: C, 60.65; H, 3.04; N, 7.53%.
2-(4-Chlorophenyl)amino-4-coumarinyl thiazole (IIId): Yellow crystals;
mp 186–188 8C; yield 64%; IR (KBr) n 3305 (NH), 1705 (C55O), 1560
1
(C55N) cm21; H NMR (DMSO-d6) d 8.55 (s, 1H, coumarinyl C4-H), 8.10
(s, 1H, NH), 8.00 (s, 1H, C5-H), 7.85–7.10 (m, 8H, ArH). Anal. calcd. for
C18H11ClN2O2S: C, 60.93; H, 3.10; N, 7.89%. Found: C, 60.71; H, 3.18;
N, 7.76%.
2-(3-Nitrophenyl)amino-4-coumarinyl thiazole (IIIe): Pale yellow crystals;
mp 168–1708C; yield 63%; IR (KBr) n 3304 (NH), 1701 (C55O), 1555
1
(C55N) cm21; H NMR (DMSO-d6) d 8.50 (s, 1H, coumarinyl C4-H), 8.20
(s, 1H, NH), 7.80(s, 1H, C5-H), 7.70–6.85 (m, 8H, ArH). Anal. calcd. for
C18H11N3O4S: C, 59.17; H, 3.01; N, 11.50%. Found: C, 59.40; H, 3.12;
N, 11.38%.
2-(2-Methylphenyl)amino-4-coumarinyl thiazole (IIIf): Yellow crystals;
mp 174–1758C; yield 61%; IR (KBr) n 3157 (NH), 1702 (C55O), 1588
1
(C55N) cm21; H NMR (DMSO-d6) d 8.57 (s, 1H, coumarinyl C4-H), 8.16
(s, 1H, NH), 7.70 (s, 1H, C5-H), 7.65–7.10 (m, 8H, ArH), 2.15 (s, 3H,

102
R. S. Koti et al.
CH3). Anal. calcd. for C19H14N2O2S: C, 68.26; H, 4.19; N, 8.38%. Found: C,
68.50; H, 4.28; N, 8.15%.
2-(2-Methoxyphenyl)amino-4-coumarinyl thiazole (IIIg): Pale yellow
crystals; mp 158–1608C; yield 56%; IR (KBr) n 3155 (NH), 1709 (C55O),
1
1588 (C55N) cm21; H NMR (DMSO-d6) d 8.60 (s, 1H, coumarinyl C4-H),
8.20 (s, 1H, NH), 7.90(s, 1H, C5-H), 7.85–7.00 (m, 8H, ArH), 3.74 (s, 3H,
OCH3). Anal. calcd. for C19H14N2O3S: C, 65.14; H, 4.00; N, 8.00%. Found:
C, 64.80; H, 3.86; N, 8.28%.
Preparation of 2-arylamino-4-coumarinyl-5-formylthiazoles
(IVa–g); General Method
Vilsmeier reagent was prepared by adding freshly distilled phosphoryl
chloride (5 mL) to dry DMF (15 mL). The mixture was stirred at 0–58C for
30 min; 2-arylamino-4-coumarinyl thiazole (IIIa–g, 0.1 mol) was added.
After 30 min, the reaction mixture was heated at 60 8C for 2 h. The mixture
was poured into a cold aqueous sodium carbonate solution and digested on
a steam bath at 908C. The product was extracted with chloroform and dried
over anhydrous sodium sulfate, and the solvent removed to get the solid,
which was recrystallized from ethanol.
Data
2-Phenylamino-4-coumarinyl-5-formyl thiazole (IVa): Colorless crystals;
mp 152–1538C; yield 60%; IR (KBr) n 3307 (NH), 1727 & 1704 (C55O),
1557 (C55N) cm21 1H NMR (DMSO-d6) d 10.34 (s, 1H, CHO), 8.67
;
(s, 1H, C4-H), 8.15 (s, 1H, NH), 7.94–7.00 (m, 9H, ArH). Anal. calcd. for
C19H12N2O3S: C, 65.51; H, 3.44; N, 8.04%. Found: C, 64.98; H, 3.54;
N, 8.24%.
2-(2-Chlorophenyl)amino-4-coumarinyl-5-formyl thiazole (IVb): Pale
yellow crystals; mp 168–1708C; yield 62%; IR (KBr) n 3318 (NH), 1727 &
1705 (C55O), 1550 (C55N) cm21 1H NMR (DMSO-d6) d 9.93 (s, 1H,
;
CHO), 8.59 (s, 1H, C4-H), 7.95 (s, 1H, NH), 7.64–7.02 (m, 8H, ArH).
Anal. calcd. for C19H11ClN2O3S: C, 59.60; H, 2.87; N, 7.32%. Found: C,
59.22; H, 2.80; N, 7.47%.
2-(3-Chlorophenyl)amino-4-coumarinyl-5-formyl thiazole (IVc): Colorless
crystals; mp 156–1588C; yield 65%; IR (KBr) n 3318 (NH), 1727 & 1705
1
(C55O), 1548 (C55N) cm21; H NMR (DMSO-d6) d 9.73 (s, 1H, CHO),
8.70 (s, 1H, C4-H), 8.03 (s, 1H, NH), 7.93–7.07 (m, 8H, ArH). Anal. calcd.
for C19H11ClN2O3S: C, 59.60; H, 2.87; N, 7.32%. Found: C, 59.93; H,
2.97; N, 7.12%.

Thiazole-Fused Diazepinones
103
2-(4-Chlorophenyl)amino-4-coumarinyl-5-formyl thiazole (IVd): Pale
yellow crystals; mp 129–1308C; yield 60%; IR (KBr) n 3314 (NH), 1725 &
1
1700 (C55O), 1540 (C55N) cm21; H NMR (DMSO-d6) d 10.05 (s, 1H,
CHO), 8.55 (s, 1H, C4-H), 8.10 (s, 1H, NH), 8.00–7.00 (m, 8H, ArH).
Anal. calcd. for C19H11ClN2O3S: C, 59.60; H, 2.87; N, 7.32%. Found: C,
59.33; H, 3.01; N, 7.52%.
2-(3-Nitrophenyl)amino-4-coumarinyl-5-formyl thiazole (IVe): Yellow
crystals; mp 145–1478C; yield 61%; IR (KBr) n 3307 (NH), 1720 & 1694
1
(C55O), 1529 (C55N) cm21; H NMR(DMSO-d6) d 10.20 (s, 1H, CHO),
8.60 (s, 1H, C4-H), 8.20 (s, 1H, NH), 8.10–7.00 (m, 8H, ArH). Anal. calcd.
for C19H11N3O5S: C, 58.01; H, 2.79; N, 10.68%. Found: C, 58.36; H, 2.68;
N, 10.52%.
2-(2-Methylphenyl)amino-4-coumarinyl-5-formylthiazole (IVf): Yellow
crystals; mp 144–1458C; yield 66%; IR (KBr) n 3306 (NH), 1716 & 1692
1
(C55O), 1540 (C55N) cm21; H NMR (DMSO-d6) d 9.79 (s, 1H, CHO),
8.60 (s, 1H, C4-H), 7.85 (s, 1H, NH), 7.60–7.12 (m, 8H, ArH), 2.22 (s, 3H,
CH3). Anal. calcd. for C20H14N2O3S: C, 66.29; H, 3.86; N, 7.73%. Found:
C, 66.00; H, 3.75; N, 7.90%.
2-(2-Methoxyphenyl)amino-4-coumarinyl-5-formylthiazole (IVg): Pale
yellow crystals; mp 140–1418C; yield 65%; IR (KBr) n 3310 (NH), 1722 &
1698 (C55O), 1550 (C55N) cm21 1H NMR (DMSO-d6) d 9.85 (s, 1H,
;
CHO), 8.55 (s, 1H, C4-H), 7.90 (s, 1H, NH), 7.80–7.00 (m, 9H, ArH), 3.68
(s, 3H, OCH3). Anal. calcd. for C20H14N2O4S: C, 63.49; H, 3.70; N, 7.40%.
Found: C, 63.12; H, 3.58; N, 7.21%.
Preparation of 2-(2-arylamino)-8-(2-hydroxybenzylidine)
6,8-dihydro7H[1,3]thiazolo[5,4-d][1,2]diazepin-7-ones (Va-g);
General Method
A solution of 2-arylamino-4-coumarinyl-5-formylthiazole (IVa–g, 0.01 mol)
and hydrazine hydrate (1.9 mL, 0.02 mol) in ethanol was refluxed for 4 h.
Excess of the solvent was removed under reduced pressure. The solid
that separated after cooling was filtered, washed with aqueous ethanol, and
recrystallized from aqueous ethanol.
Data
2-(2-Phenylamino)-8-(2-hydroxybenzylidine)6,8-dihydro7H[1,3]
thiazolo[5,4-d][1,2]diazepin-7-one (Va): Yellow crystals; mp 186–1888C;
1
yield 52%; IR (KBr) n 3339 (OH), 2962 (NH), 1621 (C55O) cm21; H

104
R. S. Koti et al.
NMR (DMSO-d6) d 11.40 (s, 1H, OH), 11.00 (s, 1H, NH), 8.74 (s, 1H, NH),
7.90 (s, 1H,55CH), 7.42–6.96 (m, 10H, ArH); 13C NMR (DMSO-d6) d 168.2,
156.1, 152.0, 146.2, 145.3, 139.5, 132.6, 130.3, 129.5, 127.7, 126.1, 125.2,
124.0, 121.3, 120.8, 119.2 and 116.6. Anal. calcd. for C19H14N4O2S: C,
62.98; H, 3.86; N, 15.46%. Found: C, 62.66; H, 3.72; N, 15.21%.
2-(2-Chlorophenyl)amino-8-(2-hydroxybenzylidine)6,8-dihydro7H
[1,3]thiazolo[5,4-d][1,2]diazepin-7-one (Vb): Yellow crystals; mp 190–
1928C; yield 55%; IR (KBr) n 3442 (OH), 3114 (NH), 1611 (C55O) cm21
;
1H NMR(DMSO-d6) d 11.42 (s, 1H, OH), 11.00 (s, 1H, NH), 8.73 (s, 1H,
NH), 7.88 (s, 1H, 55CH), 7.39–6.80 (m, 9H, ArH). Anal. calcd. for
C19H13N4ClO2S: C, 57.50; H, 3.27; N, 14.12%. Found: C, 57.20; H, 3.38;
N, 14.36%.
2-(3-Chlorophenyl)amino-8-(2-hydroxybenzylidine)6,8-dihydro7H
[1,3]thiazolo[5,4-d][1,2]diazepin-7-one (Vc): Colorless crystals; mp 158–
1608C; yield 50%; IR (KBr) n 3388 (OH), 3100 (NH), 1631 (C55O) cm21
;
1H NMR (DMSO-d6) d 11.36 (s, 1H, OH), 10.90 (s, 1H, NH), 8.66 (s, 1H,
NH), 7.92 (s, 1H, ¼CH), 7.45–6.92 (m, 9H, ArH). Anal. calcd. for
C19H13N4ClO2S: C, 57.50; H, 3.27; N, 14.12%. Found: C, 57.75; H, 3.15;
N, 14.33%.
2-(4-Chlorophenyl)amino)-8-(2-hydroxybenzylidine)6,8-dihydro7H
[1,3]thiazolo[5,4-d][1,2]diazepin-7-one (Vd): Pale yellow crystals; mp 170–
1718C; yield 51%; IR (KBr) n 3396 (OH), 3115 (NH), 1642 (C55O) cm21; 1H
NMR (DMSO-d6) d 11.44 (s, 1H, OH), 11.05 (s, 1H, NH), 8.70 (s, 1H, NH),
7.85 (s, 1H, 55CH), 7.40–6.75 (m, 9H, ArH). Anal. calcd. for
C19H13N4ClO2S: C, 57.50; H, 3.27; N, 14.12%. Found: C, 57.31; H, 3.36;
N, 14.38%.
2-(3-Nitrophenylamino)-8-(2-hydroxybenzylidine)6,8-dihydro7H
[1,3]thiazolo[5,4-d][1,2]diazepin-7-one (Ve): Yellow crystals; mp 184–
1858C; yield 55%; IR (KBr) n 3304 (OH), 3107 (NH), 1666 (C55O) cm21
;
1H NMR (DMSO-d6) d 11.35 (s, 1H, OH), 10.86 (s, 1H, NH), 8.68 (s, 1H,
NH), 7.80 (s, 1H, 55CH), 7.25–6.60 (m, 9H, ArH). Anal. calcd. for
C19H13N5O4S: C, 56.01; H, 3.19; N, 17.19%. Found: C, 56.35; H, 3.29; N,
17.46%.
2-(2-Methylphenylamino)-8-(2-hydroxybenzylidine)6,8-dihydro7H
[1,3]thiazolo[5,4-d][1,2]diazepin-7-one (Vf): Pale yellow crystals; mp 166–
1678C; yield 52%; IR (KBr) n 3329 (OH), 2950 (NH), 1610 (C55O) cm21; 1H
NMR(DMSO-d6): d 11.42 (s, 1H, OH), 11.12 (s, 1H, NH), 8.77 (s, 1H, NH),
7.95 (s, 1H, 55CH), 7.37–6.85 (m, 9H, ArH), 2.38 (s, 3H, CH3). Anal. calcd.
for C20H16N4O2S: C, 63.82; H, 4.25; N, 14.89%. Found: C, 63.56; H, 4.10;
N, 14.67%.

Thiazole-Fused Diazepinones
105
2-(2-Methoxyphenylamino)-8-(2-hydroxybenzylidine)6,8-dihydro7H
[1,3] thiazolo[5,4-d][1,2]diazepin-7-one (Vg): Colorless crystals; mp 194–
1968C; yield 50%; IR (KBr) n 3339 (OH), 2962 (NH), 1621 (C55O) cm21
1H NMR (DMSO-d6) d 11.39 (s, 1H, OH), 11.04 (s, 1H, NH), 8.83 (s, 1H,
NH), 7.86 (s, 1H, 55CH), 7.45–6.96 (m, 9H, ArH), 3.70 (s, 3H, OCH3).
Anal. calcd. for C20H16N4O3S: C, 61.22; H, 4.08; N, 14.28%. Found: C,
60.90; H, 4.28;n N, 13.99%.
;
ACKNOWLEDGMENT
Authors thank C. S. Mahajanshetti, former chairman, Department of
Chemistry, Karnatak University, Dharwad, India, for valuable suggestions
and encouragement.
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