JOURNAL OF CHEMICAL RESEARCH 2007
NOvEMBER, 619–620
RESEARCH PAPER 619
Poly{[4-(hydroxy)(tosyloxy)iodo]styrene}-promoted aromatisation of
Hantzsch 1,4-dihydropyridines
Fang-Qing Lia, Xiao-Mei Zengb and Jiang-Min Chenc*
aFaculty of Chemistry Biology and Material Science, East China Institute of Technology, 344000, Fuzhou, P.R. China
bState Key Laboratory for Chemical Fibers Modification and Polymer Materials, Donghua University, Shanghai 200051, P.R. China
cCollege of Biological and Chemical Engineering, Jiaxing University, 314001, Jiaxing, P.R. China
Hantzsch 1,4-dihydropyridines undergo smooth aromatisation on oxidation by poly{[4-(hydroxy)(tosyloxy)iodo]
styrene} (PS-HTIB) in CH2Cl2 at room temperature to afford the corresponding pyridine derivatives in good yields.
The polymeric reagent can be recycled and reused with no obvious loss of activity.
Keywords: poly{[4-(hydroxy)(tosyloxy)iodo]styrene} (PS-HTIB), aromatisation, Hantzsh 1,4-dihydropyridines, pyridine derivatives
Polymer-supported organic reagents have been applied to
the preparation of the organic molecules.1 Regeneration and
reuse of the recovered polymer-supported reagent is possible
thus providing an environmentally benign system.2 Recently
polymer-supported trivalent iodine reagents have been
synthesised and used in organic synthesis.3 Among them,
poly{[4-(hydroxy)(tosyloxy)iodo]-styrene} (PS-HTIB) is an
important reagent for the synthesis of α-tosyloxyketones.4
Hantzsch 1,4-dihydropyridines (1, Hantzsch 1,4-DHPs)
are widely used as calcium channel blockers for the
treatment of cardiovascular disorders.5 These compounds are
oxidised to pyridine derivatives by the action of cytochrome
P-450 in the liver.6 Consequently a convenient preparation of
pyridines from 1,4-DHPs is important for the identification of
metabolites. The oxidation of Hantzsch 1,4-DHPs provides
easy access to pyridine derivatives. [Hydroxy(tosyloxy)-
iodo]benzene (HTIB, PhI(OH)OTs, Koser’s reagent) had been
used7 for the oxidation of 1,4-DHPs under mild conditions,
but the by-product, iodobenzene could not be reused. On
the basis of our study of PS-HTIB,8 we now report a simple
and efficient aromatisation reaction of 1,4-DHPs for the
preparation of pyridine derivatives (Scheme 1). The present
method has the advantage of mild reaction conditions,
convenient manipulation and good yields. The polymeric
reagent could be regenerated and reused.
Reaction of Hantzsch 1,4-DHPs 1 with poly{[4-(hydroxyl)
(tosyloxy)iodo]- styrene} (PS-HTIB) in CH2Cl2 at room
temperature in 30 min gave the corresponding pyridine
derivatives 2 in good yield. The recovered poly(4-iodostyrene)
(PS-IB) was dissolved in CH2Cl2 and precipitated by the
addition of diethyl ether to purify the resin. The recovered
resin was converted to PS-HTIB according to the literature
method.7 We used the regenerated PS-HTIB in the
aromatisation reaction of 1a and found that it had the same
reactivity as the freshly prepared resin.
Experimental
Melting points were uncorrected. 1H NMR spectra were recorded on
a Bruker Avance 400 spectrometer in CDCl3 with TMS as the internal
standard. 13C NMR spectra were recorded on a Bruker AC-400
(100 MHz) spectrometer in CDCl3. IR spectra were recorded on a
Shimidazu IR-408 spectrometer. 1,4-Dihydropyridines were prepared
according to the literature procedures.11 Poly{[4-(hydroxy)(tosyloxy)
iodo]styrene} (PS-HTIB) was prepared by the literature method8
and the functional group loading was 1.90 mmol/g determined by
sulfur elemental analysis. The physical and spectroscopic data of the
products were compared with those reported in the literature.9,10
General procedure
A mixture of Hantzsch 1,4-dihydropyridine (1a, 330 mg, 1.0 mmol)
and poly{[4-(hydroxy)(tosyloxy)iodo]styrene} (PS-HTIB) (632 mg,
1.2 mmol) in dichloromethane (10 ml) was stirred at room
temperature for 30 min. After complete conversion, as indicated by
TLC, the reaction mixture was washed with water (15 ml), extracted
with CH2Cl2 (2 × 10 ml). The combined CH2Cl2 layers were dried
over anhydrous Na2SO4 and concentrated to about 5 ml under
reduced pressure. Then Et2O was added to precipitate, the poly
(4-iodostyrene) (PS-IB) which was collected to be recycled.
The filtrate was evaporated under reduced pressure to obtain the crude
product 2a, which was purified by silica gel column chromatography
(hexane/EtOAc = 5/1) to give 302 mg (92% yield) of 2a as a pale
yellow solid.
Diethyl 2,6-dimethyl-4-phenyl-3,5-pyridinedicarboxylate (2a): Pale
yellow solid; m.p. 63–64°C (Lit.9 m.p. 62–63°C). IR (KBr): 3131,
1739, 1715, 1574, 1239, 1106, 1020 cm–1. 1H NMR: δ = 7.24–7.44 (m,
5 H), 4.00 (q, J = 7.2 Hz, 4 H), 2.60 (s, 6 H), 0.98 (t, J = 7.2 Hz, 6 H).
Diethyl 4-(2-furyl)-2,6-dimethyl-3,5-pyridinedicarboxylate (2b):
Pale yellow oil (Lit.9 oil). IR (KBr): 3069, 1740, 1735, 1539, 1242,
1112, 1020 cm–1. 1H NMR (400 MHz, CDCl3): δ = 1. 22 (t, 6H,
J = 7.2 Hz), 2.57 (s, 6H), 4.24 (q, 4H, J = 7.2 Hz), 6.47–6.48 (m, 1H),
6.53–6.62 (m, 1H), 7.48–7.49 (m, 1H).
Diethyl 4-(4-methoxyphenyl)-2,6-dimethylpyridine-3,5-dicarboxylate
(2c): Colourless solid; m.p. 48–49°C (Lit.10 m.p. 49°C). IR (KBr):
1738, 1615, 1558, 1515, 1292, 1254, 1182, 1109, 1028 cm–1.
1H NMR: δ = 7.18 (d, J = 8.4 Hz, 2 H), 6.89 (d, J = 8.4 Hz, 2 H), 3.99
(q, J = 7.2 Hz, 4 H), 3.78 (s, 3 H), 2.59 (s, 6 H), 0.99 (t, J = 7.2 Hz,
6 H).
Diethyl4-(4-chlorophenyl)-2,6-dimethylpyridine-3,5-dicarboxylate
(2d): Pale yellow solid; m.p. 64–65°C (Lit.10 m.p. 64–65°C).
IR (KBr): 1737, 1559, 1231, 1108, 1044 cm–1. 1H NMR: δ = 7.31 (d,
J = 8.8 Hz, 2 H), 7.19 (d, J = 8.8 Hz, 2 H), 4.02 (q, J = 7.2 Hz, 4 H),
2.54 (s, 6 H), 0.97 (t, J = 7.2 Hz, 6 H).
In summary, PS-HTIB is an efficient oxidant for the
aromatisation of Hantzsch 1,4-dihydropyridines. This method
offers significant advantages. It has good compatibility with a
variety of substituents present in the dihydropyridine skeleton.
The results extend its potential application in organic synthesis.
O
R2
O
O
R2
O
CH2Cl2,
r. t.
R1O
Me
OR1
R1O
Me
OR1
I(OH)OTs
I
+
+
N
H
Me
N
Me
PS-HTIB
PS-IB
1
2
Scheme 1
* Correspondent. E-mail: chemcjm@yahoo.com.cn
PAPER: 07/4880
Li, Fang-Qing
