212 RESEARCH PAPER
APRILꢃꢀꢍꢅꢍ±ꢍꢅꢊ
JOURNAL OF CHEMICAL RESEARCH 2009
A route to a tetrabenzothiazole from Michael bis-addition compounds
Guowei Wang, Linghua Zhuang and Jintang Wang*
College of Sciences, Nanjing University of Technology, Nanjing 210009, P.R. China
An efficient and practical synthesis of a tetrabenzothiazole has been developed by condensation of Michael bis-
adducts with 2-aminothiophenol.
Keywords: tetrabenzothiazole, Michael addition, 2-aminothiophenol
COOR1
The benzothiazole moiety is recognised to have an importance
COOR1
in compounds of interest in medicinal chemistry,1-5
plant growth regulation6 and in industrial applications.7-10
The reported methods of benzothiazole synthesis involve
two major routes: the condensation of 2-aminothiophenol
with aldehydes,11 carboxylic acids,12 acid chlorides,13 or
esters14 and by the cyclisation of thiobenzanilides.15 Other
general methods include microwave-mediated reaction of
K2CO3
n-hexane
2
HC
R2
CH2
+
R2H2CH2C
C
CH2CH2R2
CH2
TBAB
COOR1
COOR1
2a–f R1 = CH3 or CH2CH3
R2
= CN COOCH3 or
COOCH2CH3
COOR1
E-chlorocinnamaldehydes,16
NH2
2-aminothiophenol
with
K2 CO3CH3 CN
reflux 2h
R2(H2C)2
C
(CH2)2R2
+
palladium-catalysed Suzuki biaryl coupling of 2-bromo-
benzothiazole with arylboronic acids17 and coupling of
benzothiazoles with aryl bromides,18 and the reaction between
thiophenols and aromatic nitriles.19
SH
COOR1
The Michael addition of 1,3-dicarbonyl compounds
to D,E-unsaturated esters and nitriles is one of the most
useful carbon carbon bond forming reactions and has wide
synthetic applications in organic synthesis.20 This reaction
is traditionally catalysed by strong bases that often lead to
undesirable side reactions.21 Thus, a number of milder reagents
such as Al2O3, K2CO3, rhodium complex, ruthenium complex,
clay-supported nickel bromide, quaternary ammonium
salt, and N-phenyltris(dimethylamino)iminophosphorane
immobilised on polystyrene resin at room-temperature ionic
liquids have been developed over the past few years.22-23 To
the best of our knowledge the synthesis of tetra-benzothiazoles
from Michael bis-adducts has not been reported previously.
In connection with our research programme directed
toward the synthesis of novel benzothiazole derivatives, we
GHVFULEHꢀ WKHꢀ HI¿FLHQWꢀ V\QWKHVLVꢀ RIꢀ WKHꢀ WHWUDꢁEHQ]RWKLD]ROHꢂ
(1) from Michael bis-adducts (2a–f) with anhydrous
potassium carbonate as the catalyst and tetrabutylammonium
bromide(TBAB) as the phase-transfer catalyst. The results are
reported in Table 1.
N
N
S
S
N
S
S
N
Scheme 1
General procedure for preparation of 2a
Dimethyl malonate (50 mmol) was dissolved in n-hexane (20 mL),
anhydrous potassium carbonate (100 mmol), tetrabutylammonium
bromide (0.5 g) was added, then acrylonitrile (100 mmol) was slowly
GURSSHGꢀ LQWRꢀ WKHꢀ PL[WXUHꢄꢀ 7KHꢀ UHVXOWLQJꢀ PL[WXUHꢀ ZDVꢀ UHÀX[HGꢀ IRUꢀ
12 h. 100 mL water was added to the mixture and the organic layer
was dried with magnesium sulfate and the solvent was removed in
vacuo to afford the crude compound. It was recrystallised from ethyl
acetate (15 mL). Crystals of (2a) suitable for X-ray diffraction were
obtained by slow evaporation of an alcohol solution.
Dimethyl bis(2-cyanoethyl) malonate 2a: (92%):24ꢀ0ꢄSꢄꢀꢅꢆꢇ±ꢅꢆꢈꢀ&ꢄꢀ
1H NMR (CDCl3, 500 MHz, relative to TMS) GꢉꢀꢊꢄꢋꢊꢀꢁVꢃꢀꢌ+ꢃꢀ2±&+3),
ꢍꢄꢆꢇꢀꢁWꢃꢀꢆ+ꢃꢀ±&+2±&1ꢂꢃꢀꢍꢄꢍꢌꢁWꢃꢀꢆ+ꢃꢎ&ꢎ&+2). Elemental analysis: Anal.
Calcd for C11H14N2O4: C, 55.46; H, 5.88; N, 11.76. Found: C, 55.52;
H, 5.86; N, 11.72.
,Qꢀ FRQFOXVLRQꢃꢀ DQꢀ HI¿FLHQWꢀ DQGꢀ SUDFWLFDOꢀ V\QWKHVLVꢀ RIꢀ Dꢀ
tetrabenzothiazole has been developed by condensation of
Michael bis-adducts with 2-aminothiophenol.
Experimental
1,3,3,5 Tetramethyl pentane-1,3,3,5-tetra carboxylate 2b (86%):25
0ꢄSꢄꢀ ꢏꢆ±ꢏꢌꢀ&ꢀ ꢁꢏꢆ±ꢏꢇꢀ&ꢂꢄꢀ 1H NMR (CDCl3, 500 MHz, relative to
TMS) GꢉꢀꢊꢄꢇꢆꢀꢁVꢃꢀꢌ+ꢃꢀ±&±&22±&+3ꢂꢃꢀꢊꢄꢌꢅꢀꢁVꢃꢀꢌ+ꢃꢀ±&+2±&22±&+3),
2.34 (t, 4H, CH2±&22ꢂꢃꢀꢍꢄꢅꢈꢁWꢃꢀꢆ+ꢃꢀ±&±&+2). Elemental analysis:Anal.
Calcd for C13H20O8: C, 51.32; H, 6.58. Found: C, 51.25; H, 6.62.
3,3-Dimethyl 1,5-diethyl pentane-1,3,3,5-tetra carboxylate 2c
ꢁꢋꢍꢐꢂꢉꢀ0ꢄSꢄꢀꢆꢏ±ꢆꢇꢀ&ꢄꢀ1H NMR (CDCl3, 500 MHz, relative to TMS)
Gꢉꢀ ꢆꢄꢍꢍꢀ ꢁVꢃꢀ ꢌ+ꢃꢀ ±&±&22±&+3ꢂꢃꢀ ꢊꢄꢋꢈꢀ ꢁTꢃꢀ ꢆ+ꢃꢀ ±&22±&+2±ꢂꢃꢀ ꢍꢄꢆꢍꢀ
ꢁWꢃꢀ ꢆ+ꢃꢀ ±&+2±&22±ꢂꢃꢀ ꢍꢄꢊꢅꢀ ꢁWꢃꢀ ꢆ+ꢃ±&±&+2±ꢂꢃꢀ ꢅꢄꢊꢀ ꢁWꢃꢀ ꢌ+ꢃꢀ ±&22±
CH2±&+3) Elemental analysis: Anal. Calcd for C15H24O8: C, 54.22;
H, 7.23; Found: C, 54.13; H, 7.31;
Melting points were taken on a micro-apparatus (uncorrected).
1H NMR spectra were recorded on an Avance Bruker-500 instrument
and chemical shifts in ppm are reported with TMS as the internal
standard. Mass spectra were measured on a Finnigan MAT4510
instrument. IR spectra were obtained with a Perkin-Elmer 16 PC FT-
IR spectrophotometer. Crystal structure determination was carried
out on a Enraf-Nonius CAD-4 diffractometer.
Table 1 Synthesis of Michael bis-adducts
Diethyl bis(2–cyanoethyl) malonate 2d (91%):26ꢀ 0ꢄSꢄꢀ ꢌꢍ±ꢌꢆ°C
(62°C). 1H NMR (CDCl3, 500 MHz, relative to TMS) G: 4.27 (s, 2H,
CH2), 6.53 (q, 1H, Ar), 6.61 (d, 1H, Ar), 7.15 (q, 1H, Ar). Elemental
analysis: Anal. Calcd for C13H18N2O4: C, 58.65; H, 6.77; N, 10.53.
Found: C, 58.50; H, 6.82; N, 10.46.
No.
R1
R2
Yield%
2a
2b
2c
2d
2e
2f
Me
Me
Me
Et
CN
92
86
82
91
85
82
COOMe
COOEt
CN
3,3-Diethyl-1,5-dimethyl pentane-1,3,3,5-tetra carboxylate 2e
(85%):20ꢀ 0ꢄSꢄꢀ ꢏꢍ±ꢏꢆ°C. 1H NMR (CDCl3, 500 MHz, relative
to TMS) Gꢉꢀ ꢆꢄꢅꢁTꢃꢀ ꢆ+ꢃꢀ 2±&+2±ꢂꢃꢀ ꢊꢄꢌꢁVꢃꢀ ꢌ+ꢃ2±&+3), 2.3 (t, 4H,
±&+2±&22±ꢂꢃꢀ ꢍꢄꢍꢁWꢃꢀ ꢆ+ꢃ±&±&+2±ꢂꢃꢀ ꢅꢄꢍꢁWꢃꢀ ꢌ+ꢃꢀ ±&22±&+2±&+3).
Elemental analysis: Anal. Calcd for C15H24O8: C, 54.22; H, 7.23.
Found: C, 54.16; H, 7.32;
Et
COOMe
COOEt
Et
* Correspondent. E-mail: kingwell2004@sina.com