Intramolecular amidation: Synthesis of novel imidazo[2,1-b][1,3,4] thiadiazole and imidazo[2,1-b][1,3]thiazole fused diazepinones

Article abstract of DOI:10.1016/j.tetlet.2006.02.090

Novel heterocyclic systems 2-alkyl/aryl-9-(2-hydroxybenzylidene)-7,9- dihydro-8H-[1,3,4]thiadiazolo[2′,3′:2,3]imidazo[4,5-d][1,2] diazepin-8-one and 9-(2-hydroxy-benzylidene)-3,3-dimethyl-3,4,7,9-tetrahydro-2H- 11-thia-4b,6,7,10-tetraazaindeno[1,2-a]azule

Full text of DOI:10.1016/j.tetlet.2006.02.090

Tetrahedron Letters 47 (2006) 2811–2814
Intramolecular amidation: synthesis of novel
imidazo[2,1-b][1,3,4]thiadiazole and
imidazo[2,1-b][1,3]thiazole fused diazepinones
Gundurao Kolavi, Vinayak Hegde and Imtiyaz Ahmed Khazi*
Department of Chemistry, Karnatak University, Dharwad 580003, India
Received 19 October 2005; revised 1 February 2006; accepted 9 February 2006
Available online 3 March 2006
Abstract—Novel heterocyclic systems 2-alkyl/aryl-9-(2-hydroxybenzylidene)-7,9-dihydro-8H-[1,3,4]thiadiazolo[20,30:2,3]imidazo-
[4,5-d][1,2]diazepin-8-one and 9-(2-hydroxy-benzylidene)-3,3-dimethyl-3,4,7,9-tetrahydro-2H-11-thia-4b,6,7,10-tetraazaindeno-
[1,2-a]azulene-1,8-dione are synthesized via an intramolecular amidation reaction. An interesting ring opening and cyclization of
2-alkyl/aryl-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde
and
6,6-dimethyl-8-oxo-2-(2-oxo-2H-
chromen-3-yl)-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole-3-carbaldehyde are discussed.
Ó 2006 Elsevier Ltd. All rights reserved.
Imidazo[2,1-b][1,3,4]thiadiazole,1,2 imidazo[2,1-b][1,3]-
thiazoles3,4 and diazepinone fused derivatives5,6 occupy
a prominent place in medicinal chemistry because of
their significant properties as therapeutics. This has gen-
erated much interest in the synthesis of new classes of
heterocyclic systems, thereby to explore their biological
properties.
The benzopyran-2-one 2 was used for the synthesis of
5a–f and 10. The required 3-(2-alky/arylimidazo[2,1-b]-
[1,3,4]thiadiazol-6-yl)-2H-chromen-2-ones7 were pre-
pared by the reaction of 2-amino-5-alkyl/aryl-1,3,4-
thiadiazole with 3-(bromoacetyl)coumarin 2 (Scheme 1).
The 5-carbaldehydes8 4a–f were prepared by the Vilsme-
ier–Haack reaction on 3a–f. Treatment of these
compounds with hydrazine hydrate in ethanolic KOH
under refluxing conditions provided the ring-trans-
formed derivatives9 via lactone ring opening by intra-
molecular nucleophilic attack of the –NH2 of the
intermediate hydrazone which could not be isolated.
Heterocyclic systems having a diazepinone system
linked to an imidazo[2,1-b][1,3,4]thiadiazole or an imi-
dazo[2,1-b][1,3]thiazole have not been previously re-
ported. The synthesis of such compounds having three
different fused heterocycles in a specific manner is a chal-
lenging task. Herein we report a method in which such
fused heterocyclic systems can be made through the
reaction of appropriately substituted imidazo[2,1-b]-
[1,3,4]thiadiazoles and imidazo[2,1-b][1,3]thiazoles.
A plausible initial step in the mechanism of this reaction
is intramolecular nucleophilic attack at the lactone
carbonyl of the coumarin by the primary amine group
N
O
N
R
NH2NH2H2O
NH
N
R
i. DMF / POCl3
CHO
N
N
Br
i. dry ethanol, reflux
ii. Na2CO3
N
R
N
N
N
60 oC
S
0
30
O
+
S
N
ethanolic KOH,
reflux
S
R
NH2
N
S
O
O
N
ii. aq. Na2CO3, 90 o
C
O
O
O
1a-f
O
2
HO
3a-f (53-81%)
4a-f (57-70%)
5a-f (24-36%)
R= a) ethyl, b) n-propyl, c) cyclohexyl, d) benzyl, e) 2-furyl, f) 2-thienyl.
Scheme 1.
Keywords: Thiadiazole; Imidazo[2,1-b][1,3,4]thiadiazole; Intramolecular amidation; Diazepinone.
*
Corresponding author. Tel.: +91 0836 2215286; fax: +91 836 2771275; e-mail: dr_imk@yahoo.com
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.02.090

2812
G. Kolavi et al. / Tetrahedron Letters 47 (2006) 2811–2814
R
N
N
N
NH2
N
N
CHO
R
NH
N
S
N
R
NH2NH2.H2O
Ethanol/KOH
O
N
H
O
O
N
S
S
N
N
O
O
O
R
N
R
N
N
N
N
N
NH
O
S
NH
O
S
N
dil.HCl
N
K+
HO
O
Scheme 2.
O
Br
i. dry ethanol, reflux
ii. Na2CO3
N
O
N
+
S
NH2
N
S
O
O
O
O
O
2
8 (71%)
i. DMF/POCl3
30 60 ºC
0
ii. aq.Na2CO3, 90 ºC
N
NH
N
O
CHO
S
O
N
NH2NH2H2O
O
N
S
ethanolic KOH, reflux
N
33%
O
O
HO
10 (33%)
9 (59%)
Scheme 3.
3. Andreani, A.; Granaiola, M.; Leoni, A.; Locatelli, A.;
Morigi, R.; Rambaldi, Linaz G.; Fato, R.; Bergamini, C.;
Farruggia, G. J. Med. Chem. 2005, 48, 3085–3089.
4. Andreani, A.; Leoni, A.; Locatelli, A.; Morigi, R.;
Rambaldi, M.; Recanatini, M.; Garaliene, V. Bioorg.
Med. Chem. 2000, 8, 2359–2366.
5. Gitto, R.; Orlando, V.; Quartarone, S.; De Sarro, G.; De
Sarro, A.; Russo, E.; Ferrer, G.; Chimirri, A. J. Med.
Chem. 2003, 46, 3758–3761.
leading to the formation of a lactam-diazepinone
(Scheme 2).
The versatility of this intramolecular amidation protocol
was further demonstrated by the synthesis of the
imidazothiazole fused diazepinone derivative 10 from
910–12 (Scheme 3).
In conclusion, our methodology provides a route for
the synthesis of a new heterocyclic system using easily
available precursors and reagents under very mild
conditions.
6. Hargrave, K. D.; Proudfoot, J. R.; Grozinger, K. G.;
Cullen, E.; Kapadia, S. R.; Patel, U. R.; Fuchs, V. U.;
Mauldin, S. C.; Vitous, J.; Behnke, M. L.; Klunder, J. M.;
Pal, K.; Skiles, J. W.; McNeil, D. W.; Rose, J. M.; Chow,
G. C.; Skoog, M. T.; Wu, J. C.; Schmidt, G.; Engel,
W. W.; Eberlein, W. G.; Saboe, T. D.; Campbell, S. J.;
Rosenthal, A. S.; Adams, J. J. Med. Chem. 1991, 34, 2231–
2241.
References and notes
7. General procedure for the preparation of 3-(2-alkyl/
arylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)-2H-chromen-2-ones
3a–f: 2-Amino-5-alkyl/aryl-1,3,4-thiadiazole (0.01 mol)
and 3-bromoacetyl coumarin (2.67 g, 0.01 mol) were
1. Terzioglu, N.; Gursoy, A. Eur. J. Med. Chem. 2003, 38,
781–786.
2. Gadad, A. K.; Noolvi, M. N.; Karpoormath, R. K.
Bioorg. Med. Chem. 2004, 12, 5651–5659.

G. Kolavi et al. / Tetrahedron Letters 47 (2006) 2811–2814
2813
refluxed in absolute ethanol (40 mL) for 8 h. The resultant
solid (hydrobromide) was separated by filtration. The free
base was obtained by neutralization with sodium carbon-
ate solution. It was washed with water and then recrys-
tallized from ethanol as yellow crystals. Spectral and
analytical data for 3a: Yield 69%; pale yellow solid
(ethanol); mp 164–166 °C; IR (KBr) t, 2988, 1718, 1608,
NMR (75 MHz, CDCl3) d, 13.76 (CH3), 26.22 (CH2),
116.96, 119.32, 121.29, 125.29, 125.60, 129.09, 133.12,
144.56, 147.16, 150.93, 154.31, 160.09, 169.47 (C@O
lactone) and 178.62 (C@O aldehyde); Anal. Calcd for
C16H11N3O3S: C, 59.07; H, 3.41; N, 12.92. Found: C,
59.60; H, 3.73; N, 12.99. Compound 4b: Yield 66%; pale
yellow crystalline solid (benzene + chloroform); mp 190–
192 °C; IR (KBr) t, 2873, 1715, 1670, 1607, 1569 cmꢀ1; 1H
NMR (300 MHz, CDCl3) d 1.08 (t, J = 7.2 Hz, 3H,
CH2CH2CH3), 1.93 (sextet, J = 7.2 Hz, 2H, CH2-
CH2CH3), 3.11 (t, J = 7.5 Hz, 2H, CH2CH2CH3), 7.32–
7.63 (m, 4H, coumarinyl), 8.33 (s, 1H, C4-H, coumarin),
10.19 (s, 1H, aldehyde); 13C NMR (75 MHz, CDCl3) d
13.84 (CH3), 23.06 (CH2), 34.34 (CH2), 117.01, 119.34,
121.32, 125.30, 125.64, 129.09, 133.15, 144.59, 147.23,
151.00, 154.35, 160.14, 168.18 (C@O, lactone), and 178.59
(C@O, aldehyde); Anal. Calcd for C17H13N3O3S: C, 60.17;
H, 3.86; N, 12.38. Found: C, 60.53; H, 3.81; N, 12.47.
Compound 4c: Yield 66%; pale yellow crystalline
solid(chloroform + hexane); mp 176–178 °C; IR (KBr) t,
2858, 1736, 1676, 1601 cmꢀ1; 1H NMR (300 MHz, CDCl3)
d 1.30–3.52 (m, 11H, cyclohexyl), 6.92–7.64 (m, 4H,
coumarinyl), 8.33 (s, 1H, C4-H coumarin), 10.21 (s, 1H,
aldehyde); Anal. Calcd for C20H17N3O3S: C, 63.31; H,
4.52; N, 11.07. Found: C, 63.77; H, 4.58; N, 11.30.
Compound 4d: Yield 66%; pale yellow solid (chloroform);
1454 cmꢀ1 1H NMR (300 MHz, CDCl3) d 1.46 (t, J =
;
9 Hz, 3H, CH3), 3.17 (q, J = 9 Hz, 2H, CH2), 7.27–7.51
(m, 4H, coumarinyl), 8.24 (s, 1H, C4-H, coumarin), 8.66
(s, 1H, C5-H, imidazole); Anal. Calcd for C15H11N3O2S:
C, 60.59; H, 3.73; N, 14.13. Found: C, 60.48; H, 3.91; N,
14.45. Compound 3b: Yield 64%; pale yellow crystalline
solid (ethanol); mp 170–172 °C; IR (KBr) t, 2983, 1725,
1
1602, 1569 cmꢀ1; H NMR (300 MHz, CDCl3) d 1.08 (t,
J = 7.2 Hz, 3H, CH2CH2CH3), 1.97 (sextet, J = 7.2 Hz,
2H, CH2CH2CH3), 3.14 (t, J = 7.5 Hz, 2H, CH2CH2CH3),
7.32–7.63 (m, 4H, coumarinyl), 8.33 (s, 1H, C4-H,
coumarin), 8.71 (s, 1H, C5-H imidazole); Anal. Calcd
for C16H13N3O2S: C, 61.72; H, 4.21; N, 13.50. Found: C,
61.99; H, 4.51; N, 13.67. Compound 3c: Yield 58%; yellow
amorphous solid (ethanol); mp 182–184 °C; IR (KBr) t,
2946, 1734, 1600 cmꢀ1 1H NMR (300 MHz, CDCl3) d
;
1.26–3.03 (m, 11H, cyclohexyl), 7.32–7.60 (m, 4H, cou-
marin), 8.57 (s, 1H, C4-H, coumarin), 8.63 (s, 1H, C5-H
imidazole); Anal. Calcd for C19H17N3O2S: C, 64.94; H,
4.88; N, 11.96. Found: C, 65.31; H, 5.12; N, 12.25.
Compound 3d: Yield 81%; yellow solid (ethanol), mp 196–
mp 176–178 °C; IR (KBr) t, 3058, 1732, 1674, 1605 cmꢀ1
;
1H NMR (300 MHz, CDCl3) d 4.40 (s, 2H, CH2), 6.99–
7.61 (m, 9H, ArH), 8.31 (s, 1H, C4-H, coumarin), 10.11 (s,
1H, aldehyde); Anal. Calcd for C21H13N3O3S: C, 65.10; H,
3.38; N, 10.85. Found: C, 65.19; H, 3.40; N, 11.13.
Compound 4e: Yield 57%; yellow solid (chloroform); mp
198 °C; IR (KBr) t, 3050, 1721, 1603 cmꢀ1 1H NMR
;
(300 MHz, CDCl3) d 4.41 (s, 2H, CH2), 7.29–7.55 (m, 9H,
phenyl and coumarinyl), 8.53 (s, 1H, C4-H, coumarinyl),
8.73 (s, 1H, C5-H imidazole). Anal. Calcd for
C20H13N3O2S: C, 66.84, H, 3.65; N, 11.69. Found: C,
67.04; H, 3.88; N, 11.91. Compound 3e: Yield 53%; yellow
solid (ethanol + DMF); mp 180–182 °C; IR (KBr) t, 1718,
1
166–168 °C; IR (KBr) t, 2901, 1719, 1676, 1603 cmꢀ1; H
NMR (300 MHz, CDCl3) d 6.65 (dd, JH3H4 = 3 Hz,
JH4H5 = 3.3 Hz, 1H, C4-H, furan), 7.15 (d, J = 3 Hz,
1H, C3-H, furan), 7.37–7.67 (m, 5H, coumarin, C5-H,
furan), 8.38 (s, 1H, C4-H, coumarin), 10.27 (s, 1H,
aldehyde); Anal. Calcd for C18H9N3O4S: C, 59.50; H,
2.50; N, 11.56. Found: C, 59.86; H, 2.56; N, 11.88.
Compound 4f: Yield 69%; pale yellow solid (chloroform);
1605,1510, 1489 cmꢀ1 1H NMR (300 MHz, CDCl3) d,
;
6.64 (dd, J = 3 Hz, J = 3.3 Hz, 1H, C4-H, furan), 7.15–
7.64 (m, 6H, Ar-H), 8.59 (s, 1H, C4-H, coumarin), 8.70 (s,
1H, C5-H, imidazole); Anal. Calcd for C17H9N3O3S: C,
60.89; H, 2.71; N, 12.53. Found: C, 60.97; H, 3.04; N,
12.81. Compound 3f: Yield 62%; yellow solid (ethanol);
mp 166–168 °C; IR (KBr) t, 2855, 1715, 1678, 1607 cmꢀ1
;
mp 260–262 °C; IR (KBr) t, 1724, 1614, 1554 cmꢀ1
;
1H
1H NMR (300 MHz, CDCl3) d 7.18 (dd, J = 4.5 Hz and
3.9 Hz, 1H, thiophene), 7.28–7.67 (m, 6H, coumarin, C3,
C5-H, thiophene), 8.37 (s, 1H, C4-H, coumarin), 10.27 (s,
1H, aldehyde); Anal. Calcd for C18H9N3O3S2: C, 56.98; H,
2.39; N, 11.08. Found: C, 57.18; H, 2.73; N, 11.21.
NMR (300 MHz, CDCl3) d 7.18 (d, J = 3 Hz, 1H, C4-H,
thiophene), 7.33–7.59 (m, 6H, Ar-H), 8.59 (s, 1H, C4-H,
coumarin), 8.71 (s, 1H, C5-H, imidazole); Anal. Calcd for
C17H9N3O2S2: C, 58.10; H, 2.58; N, 11.96. Found: C,
58.41; H, 2.82; N, 12.20.
9. General procedure for the preparation of 2-alkyl/aryl-
9-(2-hydroxybenzylidene)-7,9-dihydro-8H-[1,3,4]thiadiaz-
olo[20,30:2,3]imidazo[4,5-d][1,2]diazepin-8-ones 5a–f: 2-alk-
yl/aryl-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thi-
adiazole-5-carbaldehyde 4 (0.005 mol) was taken in eth-
anolic potassium hydroxide (0.55 g in 20 mL ethanol) and
refluxed with excess of hydrazine hydrate (3 mL) for 6 h.
The resulting orange solution was cooled and poured over
water, acidified with hydrochloric acid to yield a yellow
solid. The solid was separated by filtration, washed with
water and dried. Recrystallization from methanol afforded
an intense yellow solid. Spectral and analytical data for
compound 5a: Yield 36%; yellow amorphous solid (meth-
anol); mp 232–234 °C; IR (KBr) t, 3342, 3211, 1684, 1607,
8. General procedure for the preparation of 2-alkyl/aryl-6-
(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazole-
5-carbaldehydes 4a–f: The Vilsmeier reagent was prepared
by adding POCl3 (3 mL) to DMF (20 mL) at 0 °C, with
stirring. Then, 3-(2-alky/arylimidazo[2,1-b][1,3,4]thia-
diazol-6-yl)-2H-chromen-2-one (0.01 mol) was added and
the mixture stirred at 0 °C for 30 min. The mixture was
further stirred at room temperature for 2 h and then at
60 °C for an additional 2 h. The reaction mixture was then
poured into sodium carbonate solution and stirred at
90 °C for 2 h. After cooling, the mixture was diluted with
water, extracted with chloroform, the combined extracts
were washed with water, dried over anhydrous sodium
sulfate and the solvent removed under reduced pressure to
yield residual solid, which was recrystallized from an
appropriate solvent to give the crystalline solid. Spectral
and analytical data for compound 4a: Yield 70%; pale
yellow solid (benzene + chloroform); mp 188–190 °C; IR
1
1578 cmꢀ1; H NMR (300 MHz, CD3OD) d 1.34 (t, J =
3 Hz, 3H, CH3), 3.17 (q, J = 3 Hz, 2H, CH2), 6.54 (s, 1H,
C@CH), 7.27–7.59 (m, 4H, phenyl), 8.23 (s, 1H, CH@N),
11.98 (br s, 1H, NH, D2O exchangeable), 13.44 (s, 1H,
OH, D2O exchangeable); Anal. Calcd for C16H13N5O2S:
C, 56.63; H, 3.86; N, 20.64. Found: C, 56.96; H, 4.08; N,
20.81. Compound 5b: Yield 34%; yellow solid (methanol);
mp 248–250 °C; IR (KBr) t, 3322, 3302, 1689, 1621,
(KBr) t, 2849, 1715, 1668, 1607, 1477 cmꢀ1 1H NMR
;
(300 MHz, CDCl3) d 1.43 (t, J = 9 Hz, 3H, CH3), 3.12 (q,
J = 9 Hz, 2H, CH2), 7.29–7.58 (m, 4H, coumarinyl), 8.29
(s, 1H, C4-H, coumarin), 10.15 (s, 1H, aldehyde); 13C
1572 cmꢀ1 1H NMR (300 MHz, CD3OD) d 0.98 (t,
;

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G. Kolavi et al. / Tetrahedron Letters 47 (2006) 2811–2814
J = 7.2 Hz, 3H, CH2CH2CH3), 1.77 (sextet, J = 7.2 Hz,
10. Preparation of 6,6-dimethyl-2-(2-oxo-2H-chromen-3-yl)-
6,7-dihydroimidazo[2,1-b][1,3]benzothiazol-8(5H)-one 8:
This compound was prepared as per the procedure for
the preparation of 3a–f. Yield 71%; pale yellow solid
(ethanol). Mp 294–296 °C; IR (KBr) t, 1722, 1670,
2H, CH2CH2CH3), 2.97 (t, J = 7.2 Hz, 2H, CH2CH2CH3),
7.20–7.51 (m, 5H, phenyl and C@CH), 8.25 (s, 1H,
CH@N), 12.78 (br s, 1H, NH, D2O exchangeable), 13.93
(s, 1H, OH, D2O exchangeable); Anal. Calcd for
C17H15N5O2S: C, 57.78; H, 4.28; N, 19.82. Found: C,
58.10; H, 4.39; N, 19.93. Compound 5c: Yield 35%; intense
yellow solid (methanol); mp 298–300 °C; IR (KBr) t, 3349,
3137, 1698, 1602 cmꢀ1; 1H NMR (300 MHz, DMSO-d6) d
1.03–2.33 (m, 11H, cyclohexyl), 7.16–7.66 (m, 5H, phenyl,
C@CH), 8.47 (s, 1H, CH@N), 10.89 (s, 1H, NH, D2O
exchangeable), 12.97 (s, 1H, OH, D2O exchangeable); 13C
NMR (75 MHz, DMSO-d6) d 25.03 (C4 cyclohexyl), 25.35
(C3, C5 cyclohexyl), 28.84 (C2, C6 cyclohexyl), 41.84 (C1
cyclohexyl), 114.70, 116.13, 118.73, 119.83, 121.53, 125.05,
128.28, 131.76, 134.93, 136.62, 151.88, 157.47, 163.90 and
174.29 (C@O, diazepine); Anal. Calcd for C20H19N5O2S:
C, 61.05; H, 4.87; N, 17.80. Found: C, 61.14; H, 4.81; N,
17.94. Mass, FAB m/z (%), M+, 393 (10), 392 (47), 391
(50), 157 (100). Compound 5d: Yield 27%; intense yellow
solid (MeOH); mp 268–270 °C; IR (KBr) t, 3342 (broad),
1693, 1600, 1585 cmꢀ1; 1H NMR (300 MHz, DMSO-d6) d
4.31 (s, 2H, CH2), 7.18–8.38 (m, 11H, Ar-H, C@CH and
CH@N), 10.51 (br s, 1H, NH, D2O exchangeable), 13.03
(s, 1H, OH, D2O exchangeable); Anal. Calcd for
C21H15N5O2S: C, 62.83; H, 3.77; N, 17.45. Found: C,
63.33; H, 3.92; N, 17.72. Compound 5e: Yield 24%; intense
yellow solid (MeOH); mp 292–294 °C; IR (KBr) t, 3321,
3198, 1598, 1517 cmꢀ1; 1H NMR (300 MHz, DMSO-d6) d
6.63 (dd, JH3H4 = 3 Hz, JH4H5 = 3.3 Hz, 1H, C4-H,
furan), 7.14–8.28 (m, 7H, phenyl, furyl and C@CH),
8.34 (s, 1H, CH@N), 10.86 (br s, 1H, NH, D2O
exchangeable), 12.03 (s, 1H, OH, D2O exchangeable);
Anal. Calcd for C18H11N5O3S: C, 57.29; H, 2.94; N, 18.56.
Found: C, 57.64; H, 3.03; N, 18.69. Compound 5f: Yield
31%; intense yellow solid (MeOH); mp 274–276 °C; IR
1582 cmꢀ1 1H NMR (300 MHz, CDCl3) d 1.27 (s, 6H,
;
gem dimethyl), 2.61 (s, 2H, CH2), 2.95 (s, 2H, CH2CO),
7.31–7.65 (m, 4H, coumarin), 8.40 (s, 1H, C4H, couma-
rin), 8.67 (s, 1H, C5-H, imidazole); Anal. Calcd for
C20H16N2O3S: C, 65.92; H, 4.43; N, 7.69. Found: C, 65.84;
H, 4.33; N, 7.95.
11. Preparation of 6,6-dimethyl-8-oxo-2-(2-oxo-2H-chromen-
3-yl)-5,6,7,8-tetrahydroimidazo[2,1-b][1,3]benzothiazole-
3-carbaldehyde 9: This compound was prepared by the
Vilsmeier–Haack reaction of 6,6-dimethyl-2-(2-oxo-2H-
chromen-3-yl)-6,7-dihydroimidazo[2,1-b][1,3]benzothiazol-
8 (5H)-one, as described for imidazo[2,1-b][1,3,4]thiadiaz-
oles 3a–f. Yield 59%; pale yellow needles (chloroform); mp
296–298 °C; IR (KBr) t, 2880, 1716, 1676, 1645, 1609,
1565 cmꢀ1 1H NMR (300 MHz, CDCl3) d 1.27 (s, 6H,
;
gem dimethyl), 2.66 (s, 2H, CH2), 3.59 (s, 2H, CH2CO),
7.43–7.76 (m, 4H, coumarin), 8.41 (s, 1H, C4-H, couma-
rin), 9.86 (s, 1H, aldehyde); 13C NMR (75 MHz, CDCl3) d
28.5 gem dimethyl), 31.1 (CH2), 35.5 (C), 50.8 (CH2CO),
113.1, 116.9, 117.3, 118.8, 126.2, 126.8, 126.9, 129.7, 134.8,
146.4, 147.7, 154.5, 165.8 (C@O lactone), 178.5 (C@O
aldehyde) and 193.3 (C@O ketone); Anal. Calcd for
C21H16N2O4S: C, 64.27; H, 4.11; N, 7.14. Found: C, 64.42;
H, 4.35; N, 7.47.
12. Preparation of 9-(2-hydroxy-benzylidene)-3,3-dimethyl-
3,4,7,9-tetrahydro-2H-11-thia-4b,6,7,10-tetraaza-indeno[1,2-
a]- azulene-1,8-dione 10: This compound was prepared as
per the procedure for the preparation of 5a–f. Yield 33%;
pale yellow solid (methanol); mp 272–274 °C; IR (KBr) t,
3426, 3313, 1694, 1661, 1624, 1573 cmꢀ1 1H NMR
;
(300 MHz, CD3OH) d 1.28 (s, 6H, gem dimethyl), 2.61
(s, 2H, CH2), 2.99 (s, 2H, COCH2), 7.30–7.70 (m, 5H,
phenyl and C@CH), 8.28 (s, 1H, CH@N), 11.23 (br s, 1H,
NH, D2O exchangeable), 13.54 (s, 1H, OH, D2O
exchangeable); Anal. Calcd for C21H18N4O3S: C, 62.05;
H, 4.46; N, 13.78. Found: C, 62.50; H, 4.82; N, 13.91.
Mass, ESI, m/z (%), 406 (20), 404 (100).
(KBr) t, 3365, 1698, 1606, 1527 cmꢀ1
;
1H NMR
(300 MHz, DMSO-d6) d 7.27–7.99 (m, 8H, thienyl, phenyl
and C@CH), 8.52 (s, 1H, CH@N), 11.82 (s, 1H, NH, D2O
exchangeable), 13.08 (s, 1H, OH, D2O exchangeable);
Anal. Calcd for C18H11N5O2S2: C, 54.95; H, 2.82; N,
17.80. Found: C, 54.88; H, 2.87; N, 18.03.