A novel three-component reaction involving benzothiazole, dialkyl acethylenedicarboxylate and 1,3-dicarbonyl compounds or anthrone

Article abstract of DOI:10.3184/174751912X13304271635260

The 1,3-dipolar intermediates generated by addition of benzothiazole, to dialkyl acethylenedicarboxylates are trapped by 1,3-dicarbonyl compounds such as 1,3-dimethyl barbituric acid, 1,3-diphenyl-1,3-propandione, acetylacetone, 5,5-dimethylcyclohexane-1,3-dione and indandione. The reactions proceeded smoothly at room temperature, and with good yields. The synthesised compounds have been characterised by elemental analyses and spectroscopic studies.

Full text of DOI:10.3184/174751912X13304271635260

166 RESEARCH PAPER
MARCH, 166–168
JOURNAL OF CHEMICAL RESEARCH 2012
A novel three-component reaction involving benzothiazole, dialkyl
acethylenedicarboxylate and 1,3-dicarbonyl compounds or anthrone
Mahmoud Nassiri*
Faculty of Marine Science, Chabahar Maritime University, PO Box 99717-56499, Chabahar, Iran
The 1,3-dipolar intermediates generated by addition of benzothiazole, to dialkyl acethylenedicarboxylates are trapped
by 1,3-dicarbonyl compounds such as 1,3-dimethyl barbituric acid, 1,3-diphenyl-1,3-propandione, acetylacetone,
5,5-dimethylcyclohexane-1,3-dione and indandione. The reactions proceeded smoothly at room temperature, and
with good yields. The synthesised compounds have been characterised by elemental analyses and spectroscopic
studies.
Keywords: benzothiazole, dialkyl acetylenedicarboxylate, 1,3-dicarbonyl compounds, anthrone, formation of C=C
Heterocyclic compounds occur very widely in nature and
are essential to life.Their synthesis has been subject of great
interest due to their wide applicability.1,2 Some heterocyclic
compounds containing a thiazole ring in their structures have
important applications in pharmaceutical as well as in agro-
chemical chemistry.3–5 Compounds with benzothiazole skele-
tons are of paramount interest because of their antitumour,
anticancer, and antibacterial activities.6–10 In addition, the benzo-
thiazole nucleus is a key element in some thermally stable
rigid-rod polymers, possessing high tensile strength and
modulus.11 N-Heterocycles are known to form zwitterions with
activated acetylenes such as dimethyl acetylenedicarboxyl-
ate.12 This type of zwitterion can be trapped by a variety
of electrophiles and proton donors such as phenols.13,14 In
the current work, the reactions of benzothiazole with dialkyl
acetylenedicarboxylate in the presence of 1,3-dicarbonyl com-
pounds or anthrone are reported (see Scheme 1 and Table 1).
Scheme 1 shows a reaction with 1,3-dimethyl barbituric acid
as an example.
Results and discussion
The reactions of benzothiazole 1 with dialkyl acetylenedicar-
boxylates 2 in the presence of 1,3-dicarbonyl compounds or
anthrone 3, proceeded smoothly at ambient temperature in
CH2Cl2, and were completed within five hours. The reactions
were carried out by first mixing the benzothiazole and 1,3-
dicarbonyl compounds or anthrone and then adding the acety-
1
lenic ester slowly. The H and 13C NMR spectra of the crude
products clearly indicated the formation of compounds 4a–g.
No product other than 4a–g could be detected by NMR spec-
troscopy. The structures of newly synthesised compounds
1
4a–g were deduced from their elemental analysis, IR, H
NMR, 13C NMR, and mass spectrometricdata. The 500 MHz
1H NMR spectrum of 4a exhibited four signals corresponding
Scheme 1
* Correspondent. E-mail: mdnassiri@yahoo.com

JOURNAL OF CHEMICAL RESEARCH 2012 167
Table 1 Reaction between benzothiazole with acetylenic esters
In summary, I report a simple and one-pot procedure for
the formation of C=C from reaction between benzothiazole
and dialkyl acetylenedicarboxylate in the presence of 1,3-
dicarbonyl compounds or anthrone. The present procedure has
the advantage that not only is the reaction performed under
neutral conditions, but also the reactants can be mixed without
any prior activation or modification. It seems that this proce-
dure is very useful to functionalise benzothiazole in a one-pot
operation.
in the presence of 1,3-dicarbonyl compounds or anthrone
Entry
R
Producta
Yield/%
1
Me
91
Experimental
2
3
4
5
6
7
Et
89
92
86
90
90
85
All chemicals were purchased from Fluka (Buchs, Switzerland) and
were used without further purification. Melting points were measured
on an Electrothermal 9100 apparatus. Elemental analyses for C, H and
N were performed using a Heraeus CHN-O-Rapid analyser. Mass
spectra were recorded on a GCMS-QP5050A mass spectrometer
operating at an ionisation potential of 70 eV. The H and 13C NMR
1
Me
Me
Me
Me
Me
spectra were obtained with a BRUKER DRX-500 AVANCE instru-
ment using CDCl3 as solvent and TMS as internal standard at 500.1
and 125.8 MHz respectively. IR spectra were recorded on a Shimadzu
IR-460 spectrometer.
General procedure
To a magnetically stirred solution of benzothiazole (1.0 mmol) and
1,3-dimethyl barbituric acid (0.16 g, 1 mmol) in CH2Cl2 (10 mL) was
added, dropwise, a mixture of dimethyl acetylenedicarboxylate
(1 mmol) in CH2Cl2 (5 mL) at –10 °C over 5 min. After 5 h stirring at
ambient temperature, the whole reaction mixture solidified into a
brown solid. The solvent was then removed under reduced pressure
and product washed with cold n-hexanee (2×5 mL). The residue was
recrystallised from 2:1 n-hexane/EtOAc.
Dimethyl 2-(2-(tetrahydro-1,3-dimethyl-2,4,6-trioxopyrimidin-5(6H)-
ylidene)benzo[d] thiazol-3(2H)-yl)fumarate (4a): Brown powder,
yield 91%, 0.39g, m.p. 133–135 °C, IR (νmax, cm–1): 1742, 1635 and
1620 (C=O). MS, m/z (%) = 431 (M, 8), 372 (M–CO2Me, 31), 313
(M–2CO2Me, 15), 143 (C6H7O4, 19), 154 (C6H6N2O3, 47), 134
(C7H4NS, 29). Anal. Calcd for C19H17N3O7S (431.34): C, 52.91; H,
1
3.97; N, 9.74. Found: C, 52.79; H, 4.00; N, 9.78%. H NMR (500.1
MHz, CDCl3), δH 3.29 (3H,s,NMe), 3.44 (3H, s, NMe), 3.65(3H, s,
OMe), 3.79 (3H, s, OMe), 6.78 (1H, s, N–C=CH–CO2Me), 6.90–8.08
(4Haro). 13C NMR (125.8 MHz, CDCl3), 32.7 (NMe), 33.3 (NMe),
50.3 (OMe), 50.4 (OMe), 78.8 (N–C=CH–CO2Me), 98.2 (S–C=C),
121.9 (1Caro), 124.4 (N–C=CH–CO2Me), 125.7, 126.1, 127.0 and
131.2 (4Caro), 150.7 (N–CO–N), 151.8 (1Caro), 153.1 (S–C=C), 167.9
(O=C-C-C=O), 170.3 and 170.6 (2C=O, ester).
a Z-stereochemistry.
Diethyl 2-(2-(tetrahydro-1,3-dimethyl-2,4,6-trioxopyrimidin-5(6H)-
ylidene)benzo[d] thiazol-3(2H)-yl)fumarate (4b): Brown powder,
yield 89%, 0.41g, m.p. 125–127 °C, IR (νmax, cm–1): 1740, 1635 and
1630 (C=O), MS, m/z (%) = 459 (M, 5), 386 (M–CO2Et, 44), 369
(M–2OEt, 67), 154 (C6H6N2O3, 39), 134 (C7H4NS, 26), 45 (OEt, 17).
Anal. Calcd for C21H21N3O7S (459.39): C, 54.91; H, 4.61; N, 9.14.
Found: C, 55.02; H, 4.65; N, 9.19%. 1H NMR (500.1 MHz, CDCl3),
δH 1.13 (3H, t, 3JHH = 7.3 Hz, OCH2CH3) and 1.28 (3H, t, 3JHH = 7.3 Hz,
OCH2CH3), 3.26 (3H, s, NMe), 3.44 (3H, s, NMe), 4.16 (4H, m,
2ABX3 system, 2OCH2CH3), 6.58 (1H, s, N–C=CH–CO2CH2CH3),
6.71–7.98 (4Haro). 13C NMR (125.8 MHz, CDCl3), 13.9 (OCH2CH3),
14.1 (OCH2CH3), 28.4 (NMe), 29.4 (NMe), 61.1 (OCH2CH3), 62.3
(OCH2CH3), 73.7 (N–C=CH–CO2CH2CH3), 100.8 (S–C=C), 120.9
(1Caro), 124.3 (1C, N–C=CH–CO2CH2CH3), 125.9, 126.5, 128.2 and
130.3, (4Caro), 149.9 (N–CO–N), 151.9 (1Caro), 153.9 (S–C=C), 164.8
(O=C-C-C=O), 170.2 and 171. 5 (2C=O, ester).
Dimethyl 2-(2-(2,4-dioxopentan-3-ylidene)benzo[d]thiazol-3(2H)-yl)
fumarate (4c):Yellow powder, yield 92%, 0.35g, m.p. 119–121 °C, IR
(νmax, cm–1): 1728 and 1646 (C=O), MS, m/z (%) = 316 (M–CO2Me,
72), 277 (M–C5H6O2, 39), 257 (M–2CO2Me, 33), 143 (C6H7O4, 62),
98 (C5H6O2, 25), 59 (CO2Me, 13). Anal. Calcd for C18H17NO6S
(375.33): C, 57.60; H, 4.56; N, 3.73. Found: C, 57.38; H, 4.49; N,
3.77%. 1H NMR (500.1 MHz, CDCl3), δH 1.83 (3H, s, Me), 2.27 (3H,
s, Me), 3.65 (3H, s, OMe), 3.79 (3H, s, OMe), 6.63 (1H, s, N–C=CH–
CO2Me), 6.63-7.97 (4Haro). 13C NMR (125.8 MHz, CDCl3), δC 23.3
(2Me), 51.8 (OCH3), 52.2 (OCH3), 73.2 (N–C=CH–CO2Me), 104.2
(S–C=C), 121.9 (1Caro), 123.5 (N–C=CH–CO2Me), 125.5, 125.9,
126.1 and 133.7 (4Caro), 153.0 (S–C=C), 154.1 (1Caro), 163.6 and
165.2 (C=O, ester), 189.5 (2C=O).
to methyl groups (δ 3.29, 3.44 ppm, each 3H, s, NMe and δ
3.65, 3.79 ppm, each 3H, s, OMe) and one due to an olefinic
proton (δ 6.78 ppm, 1H, s, N–C=CH). Aromatic protons, with
multiplets at δ 6.90–8.08 ppm were assigned to the benzothia-
zole moiety. The 13C NMR spectrum of 4a showed 19 distinct
resonances in agreement with the proposed structure. In addition,
product 4a displayed 13C NMR resonances at δ 78.7, 124.4,
98.2 and 153.1 ppm, for the N–C=CH–CO2Me, N–C=CH–
CO2Me, S–C=C and S–C=C units respectively.15–21 The 13C
NMR showed peaks at δ 167.9, 170.3 and 170.6 ppm for the
C=O groups.
1
The H and 13C NMR spectra of 4b–g are similar to those
of 4a except for the carbonyl moieties, which exhibited char-
acteristic resonances in appropriate regions of the spectrum.
The 1H NMR of each of the isolated products 4a–g exhibited a
N–C=CH proton signal at about 6.58–6.78 ppm, which is in
agreement with the ( Z) configuration22–24 for the vinyl moiety
in 4a–g. (see Scheme 1 and Table 1).
Although the mechanistic details of the reaction are not
known, a plausible rationalisation may be advanced to explain
the product formation (Scheme 1). Presumably, the zwitterionic
intermediate formed from benzothiazole and dialkyl acetyl-
enedicarboxylate is protonated by 3 to furnish intermediate
6, which is attacked by carbanion 7 to produce 8. Compound
8 can then undergo oxidation by air to give the observed
product 4.

168 JOURNAL OF CHEMICAL RESEARCH 2012
Dimethyl 2-(2-(1,3-dioxo-1,3-diphenylpropan-2-ylidene)benzo[d]
thiazol-3(2H)-yl)fumarate (4d): Yellow powder, yield 86%, 0.43 g,
m.p. 139–141 °C, IR (νmax, cm–1): 1727 and 1630 (C=O). MS, m/z (%)
= 484 (M–Me, 54), 440 (M–CO2Me, 69), 437 (M-2OMe, 30), 277
(M–C15H10O2, 36), 143 (C6H7O4, 22), 134 (C7H4NS, 41), 59 (CO2Me,
18). Anal. Calcd for C28H21NO6S (499.47): C, 67.33; H, 4.24; N, 2.80.
Found: C, 67.19; H, 4.19; N, 2.84%. 1H NMR (500.1 MHz, CDCl3),
δH 3.51 (3H, s, OMe), 3.78 (3H, s, OMe), 6.86 (1H, s, N–C=CH–
CO2Me), 6.89–8.99 (14Haro). 13C NMR (125.8 MHz, CDCl3), 51.2
(CO2Me), 52.3 (CO2Me), 74.1 (N–C=CH–CO2Me), 102.1 (S–C=C),
122.4 (1Caro), 124.2 (N–C=CH–CO2Me), 125.9, 126.5, 127.1, 128.3,
128.8, 128.8, 129.8, 129.9, 130.2, 131.8, 134.4, 135.0, 136.2 and
137.1 (16Caro), 154.0 (S–C=C), (1Caro), 154.6 167.0 and 167.5 (2C=O,
ester), 192.1 and 193.1 (2C=O).
(N–C=CH–CO2Me), 125.6, 126.2, 127.0, 127.2, 127.5, 128.5, 131,9,
132.8, 133.4, 133.6, 134.1, 140.5, 141.4 and 143.2 (16Caro), 153.2
(S–C=C), 154.1 (1Caro), 166.6 and 168.2 (C=O, ester), 184.3 (2C=O).
We gratefully acknowledge financial support from the Research
Council of the Chabahar Maritime University.
Received 27 October 2011; accepted 10 February 2012
Paper 1100957 doi: 10.3184/174751912X13304271635260
Published online: 22 March 2012
References
1
E. Conchon, F. Anison, B. Aboba and M. Prudhomme, J. Med. Chem.,
2007, 50, 4669.
Dimethyl2-(2-(4,4-dimethyl-2,6-dioxocyclohexylidene)benzo[d]thi-
azol-3(2H)-yl) fumarate (4e): Brown powder, yield 90%, 0.37 g, m.p.
128–130 °C, IR (νmax, cm–1): 1730, 1645 and 1632 (C=O). MS, m/z
(%) = 415 (M, 5), 400 (M–Me, 12), 356 (M–CO2Me, 58), 277 (M–
C8H10O2, 35), 143 (C6H7O4, 71), 138 (C8H10O2, 65), 134 (C7H4NS, 41),
59 (CO2Me, 29) . Anal. Calcd for C21H21NO6S (415.39): C, 60.72; H,
2
G. Blanco, A. Fernandez-Mato, J.M. Quintela and C. Peinador, Synthesis,
2009, 3, 438.
3
4
I. Yavari, Z. Hossaini, S. Souri and S. Seyfi, Mol Divers., 2009, 13, 439.
K. Schulze, F. Rihter, R. Seisheit, R. Krause and M. Muhlstadt, J. Prakt.
Chem., 1980, 322, 629.
1
5
6
7
D. L. Layman and J. P. Scovill, J. Med. Chem., 1983, 26, 35.
S. Pal, G. Patra and S. Bhunia, Synth Commun., 2009, 39, 1196.
Y. Heo, Y.S. Song, B.T. Kim and J.N. Heo, Tetrahedron Lett., 2006, 47,
3091.
5.09; N, 3.37. Found: C, 60.79; H, 5.06; N, 3.44%. H NMR (500.1
MHz, CDCl3), δH 1.02 (2H, m, CH2), 1.08 (2H, m, CH2), 2.24 (3H, s,
Me), 2.51 (3H, s, Me), 3.52 (3H, s, OMe), 3.57 (3H, s, OMe), 6.70
(1H, s, N–C=CH–CO2Me), 6.95–7.98 (4Haro). 13C NMR (125.8 MHz,
CDCl3), 26.9 and 27.2 (CMe2), 28.2 (CMe2), 45.6 (CH2), 46.3 (CH2),
50.3 (OMe), 52.6 73.7 (N–C=CH–CO2Me), 103.3 (S–C=C), 121.1
(1Caro), 123.5 (1C, N–C=CH–CO2Me), 125.6, 126.2, 128.6 and 133.6
(4Caro), 153.0 (S–C=C), 154.1 (1Caro), 165.8 (C=O, ester), 168.2 (C=O,
ester), 198.8 (C=O), 203.7 (C=O).
8
A. Kamal, K.S. Reddy, M.N.A. Khan, R.V.C.R.N.C. Shetti, M.J. Ramaiah,
S.N.C.V.L. Pushpavalli, C. Srinivas, M.P. Bhadra, M. Chourasia, G.N.
Sastry, A. Juvekar, S. Zingde and M. Barkume, Bioorg. Med. Chem., 2010,
18, 4747.
9
S.S. Patil and V.D. Bobade, Synth Commun., 2010, 40, 206.
10 L. jin, B. Song, G. Zhang, R. Xu, S. Zhang, X. Gao, D. Hu and S. Yang,
Bioorg. Med. Chem. Lett., 2006, 16, 1537.
Dimethyl 2-(2-(1,3-dioxo-1H-inden-2(3H)-ylidene)benzo[d]thiazol-
3(2H)-yl)fumarate (4f): Brown powder, yield 90%, 0.38 g, m.p. 143–
145 °C, IR (νmax, cm–1): 1730, 1722 and 1650 (C=O). MS, m/z (%) =
421 (M, 7), 390 (M–OMe, 22), 362 (M–CO2Me, 73), 303 (M–
2CO2Me, 54), 277 (M–C9H4O2, 18), 144 (C9H4O2, 47), 134 (C7H4NS,
69). Anal. Calcd for C22H15NO6S (421.36): C, 62.71; H, 3.59; N, 3.32.
Found: C, 62.87; H, 3.56; N, 3.37%. 1H NMR (500.1 MHz, CDCl3),
δH 3.41 (3H, s, OMe), 3.68 (3H, s, OMe), 6.65 (1H, s, N–C=CH–
CO2Me), 6.79–8.31 (8Haro). 13C NMR (125.8 MHz, CDCl3), δC 51.5
(OMe), 53.2 (OMe), 74.0 (N–C=CH–CO2CH3), 110.1 (S–C=C),
121.1 and 121.9 (2Caro), 123.2 (N–C=CH–CO2CH3), 123.7, 125.5,
126.0, 126.1, 126.2, 127.2, 127.4, , 135.6 and 143.3 (9Caro), 153.1
(S–C=C), 154.0 (1Caro), 169.5 (2C=O, ester), 170.9 (2C=O, ester),
197.3 (2C=O).
11 W. Huang, Y. Tan, M.W. Ding and G.F. Yang, Synth. Commun., 2007, 37,
369.
12 H.J. Dillinger, G. Fengler, D. Schumann and E. Winterfeldt, Tetrahedron,
1974, 30, 2561.
13 I. Yavari, L. Moradi, A. Mokhtarporiani-Sanandej and A. Mirzaei, Helv.
Chim. Acta, 2006, 90, 392.
14 I. Yavari, A. Mirzaei and L. Moradi, Synth Commun., 2010, 40, 2407.
15 I. Yavari, Z. Hossaini, M. Sabbaghan and M. Ghazanfarpour-Darjani,
Monatsh Chem., 2007, 138, 677.
16 I. Yavari, F. Nasiri and H. Djahaniani, Phosphorous, Sulfur, Silicon Relat.
Elem., 2003, 178, 2627.
17 M. Nassiri, R. Heydari, N. Hazeri, S.M. Habibi-Khorassani, M.T.
Maghsoodlou and F. Jalili Milani, J. Chem. Res., 2010, 34, 365.
18 M.T. Maghsoodlou, S.M. Habibi-Khorassani, N. Hazeri, G. Marandi and
H.R. Bijanzadeh, J. Chem. Res., 2006, 73.
Dimethyl 2-(2-(10-oxoanthracen-9(10H)-ylidene)benzo[d]thiazol-
3(2H)-yl)fumarate (4g):Yellow powder, yield 85%, 0.40 g, m.p. 137–
139 °C, IR (νmax, cm–1): 1732 and 1640 (C=O). MS, m/z (%) = 469 (M,
4), 438 (M–OMe, 16), 410 (M–CO2Me, 33), 277 (M–C14H8O, 14),
192 (C14H8O, 62), 143 (C6H7O4, 49), 134 (C7H4NS, 71). Anal. Calcd
for C27H19NO5S (469.45): C, 69.08; H, 4.08; N, 2.97. Found: C, 68.97;
19 I. Yavari, N. Hazeri, M.T. Maghsoodlou, N. Zabarjad-Shiraz, Monatsh.
Chem., 2001, 132, 683.
20 E. Breitmaier and W.Voelter, Carbon-13 NMR spectroscopy: high-resolution
methods and applications in organic chemistry and biochemistry, 3rd edn,
VCH, Weinheim, 1987, p. 282.
21 J.S. Bae, S.Y. Gwon, Y.A. Son and S.H. Kim, Dyes Pigm., 2009, 83, 324.
22 I. Yavari, A.R. Alboezi, B. Mohtat and F. Nourmohammadian, Synth
Commun., 2008, 38, 703.
23 E.L. Eliel and S.H. Wilen, Stereochemistry of organic compounds. Wiley,
New York, 1994, 570.
1
H, 4.04; N, 3.01%. H NMR (500.1 MHz, CDCl3), δH 3.51 (3H, s,
OMe), 3.79 (3H, s, OMe), 6.68 (1H, s, N–C=CH–CO2Me), 6.88–8.73
(12Haro), 13C NMR (125.8 MHz, CDCl3), 52.0 (OMe), 53.2 (OMe),
69.9 (N–C=CH–CO2Me), 106.2 (S–C=C), 121.9 (1Caro), 123.5
24 M. Nassiri, J. Chem. Res., 2011, 35, 437.

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