An efficacious protocol for the oxidation of 3,4-dihydropyrimidin-2(1H)- ones using pyridinium chlorochromate as catalyst

Article abstract of DOI:10.1071/CH07432

4-Unsubstituted as well as 4,6-aryl/alkyl-3,4-dihydropyrimidin-2(1H)-ones were oxidized under neutral conditions using pyridinium chlorochromate to obtain the corresponding pyrimidin-2(1H)-ones in a synthetically useful manner.

Full text of DOI:10.1071/CH07432

Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2008, 61, 910–913
www.publish.csiro.au/journals/ajc
An Efficacious Protocol for the Oxidation
of 3,4-Dihydropyrimidin-2(1H)-ones using
Pyridinium Chlorochromate as Catalyst
Kamaljit SinghA,B and Kawaljit SinghA
AOrganic Synthesis Laboratory, Department of Applied Chemical Sciences & Technology,
Guru Nanak Dev University, Amritsar 143 005, India.
BCorresponding author. Email: kamaljit19in@yahoo.co.in
4-Unsubstituted as well as 4,6-aryl/alkyl-3,4-dihydropyrimidin-2(1H)-ones were oxidized under neutral conditions using
pyridinium chlorochromate to obtain the corresponding pyrimidin-2(1H)-ones in a synthetically useful manner.
Manuscript received: 15 December 2007.
Final version: 13 September 2008.
Introduction
pyrimidin-2(1H)-ones using pyridinium chlorochromate (PCC)
as catalyst under neutral reaction conditions.
Structurally diverse 4-substituted 3,4-dihydropyrimidin-2(1H)-
ones (DHPMs), such as Hantzsch 1,4-dihydropyridines (DHPs),
have emerged as effective calcium antagonists.[1] These com-
pounds inhibit the movement of calcium through certain mem-
brane channels.[2] Unlike DHPs, which depict a facile in-vivo
and in-vitro oxidation,[3] a key step in the initial metabolism
of DHP-based drugs, structurally related DHPMs are resistant.
Many attempts to oxidize (i.e., dehydrogenate) DHPMs using
several different oxidizing agents failed. For example, oxidants
such as ceric ammonium nitrate,[4] NaNO2 in acetic acid,[5]
KMnO4,[6] MnO2,[7] 2,3-dichloro-5,6-dicyanobenzoquinone,
and chloranil[8] are inefficient for the conversion of DHPMs
into corresponding pyrimidines. Use of Eynde’s procedure[9]
to obtain pyrimidines is not only multistep, but also fur-
nishes moderate yields of the desired products. CuCl2/tert-
butylhydroperoxide (TBHP)/K2CO3,[10] Jones reagent,[11] and
potassium peroxydisulfate[12] have also been employed for
the oxidation of DHPMs. In these protocols, the desired de-
hydrogenation is attended by C4 dealkylation in the case of
a secondary alkyl or benzyl group.[13] In a recently disclosed
method that employs hydrated Co(NO3)2/K2S2O8 in aqueous
acetonitrile,[14] the formation of rather unusual products result-
ing from C6 dealkylation along with dehydrogenation has been
reported. Thus, an efficient and direct route that leads to the
exclusive formation of pyrimidin-2(1H)-ones through oxidation
of DHPMs is still not available. In this manuscript, we describe
our findings on the selective and mild oxidation of DHPMs into
Results and Discussion
We have recently reported a highly regio- as well as
chemo-selective scaffold decoration of 4-substituted-3,4-
dihydropyrimidin-2(1H)-ones (DHPMs)/thiones using a flexible
C6 lithiation–substitution protocol.[15] An extension of this
site-selective lithiation–substitution sequence culminated in the
regioselective N3-acylation approach,[16] the synthetic utility of
which was demonstrated by choosing several acylating agents.
In continuation of our interest in obtaining DHPMs as poten-
tial candidates for calcium antagonistic evaluation as well as
for structure activity relationship studies, pyrimidine-2(1H)-one
precursors were required.
Pyrimidine-2(1H)-ones 1 undergo regioselective nucleo-
philic addition reactions[17] at C4 (Scheme 1) and furnish
DHPMs bearing tailor-made (4-aryl/heterocyclyl/alkyl) frag-
ments, not available through the traditional three-component
Biginelli condensation.[18] We obtained 1 through oxidation of
DHPMs 2 (R4 = H) using nitric acid[19] which is tedious, both
from the point of view of running the reaction as well as the
isolation of products from the highly acidic solution. To further
widen the scope of C4 elaboration, 1 was required in multi-
gram quantities. In the absence of a general selective protocol,
we found that pyrimidine-2(1H)-ones could be obtained through
the N3–C4 oxidation of DHPMs 2 with PCC[20] under neutral
reaction conditions and in a synthetically useful manner. The
R2
O
R2
O
O
(R2MgX/R2Li)
(X ϭ O, S)
R1O
N
R1O
N
R1O
NH
PCC/DCM/r.t.
55–79%
R4
N
O
R4
N
X
R4
N
R3
2
X
(R2 ϭ alkyl/aryl/heterocyclyl)
(X ϭ O)
R3
R3
3
1
Scheme 1. C4 elaboration and PCC-catalyzed oxidation of structurally diverse 3,4-dihydropyrimidin-2(1H)-ones 2.
© CSIRO 2008 10.1071/CH07432 0004-9425/08/110910

Oxidation of 3,4-Dihydropyrimidin-2(1H)-ones using PCC
911
Table 1. Synthesis of pyrimidin-2(1H)-ones 3 through PCC oxidation of 2
Entry
Pyrimidin-2(1H)-ones 3
R2
Reaction time [h]
Isolated yieldsA,B [%]
R1
R3
R4
a
b
c
d
e
f
g
h
i
j
k
l
m
n
Et
Et
Et
Et
Me
Et
Et
H
H
Ph
Ph
H
Me
H
Me
H
H
Me
H
H
H
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
C3H7
Ph
20
18
26
16
18
25
25
23
21
20
20
23
19
20
79
63
63
60C
71
Ph
4-MeOC6H4
4-NO2C6H4
3,4,5-(MeO)3C6H2
3-NO2C6H4
Me
Me
Ph
Me
C5H11
60
60C
60C
55C
69
Et
(Me)2CH
Et
Me
Et
Et
Et
65
70
71
62
H
H
H
Me
AYields based on isolated purified products.
B3.0 equivalents of PCC were used.
C4.0 equivalents of PCC were required for complete conversion.
R2
R2
R2
O
R2
O
O
O
H
ϩ
NH
R1O
N
1
R1O
NH
R1O
ϪHϩ
Cr5ϩ
R O
NH
ϪHϩ
R4
N
R3
O
R4
N
R3
X
R4
N
R3
2
X
R4
N
R3
O
Cr6ϩ
Cr5ϩ
Cr4ϩ
3
Scheme 2. Proposed mechanism for the formation of 3.
reaction requires 3.0 equivalents of PCC to drive the oxidation to
completion; however, if 1.0 equivalent of the reagent is used, pro-
longed stirring is required. However, the modest excess of PCC
is largely offset by the simplicity of the operation and reason-
ably good yields (Table 1) of the purified products. Furthermore,
in comparison with literature protocols, no side product arising
from C4/C6 dealkylation[14] was formed.
was used as such. However, in using PCC, reactions did not
proceed to completion when an equimolar quantity of PCC was
employed. As the literature reports suggest,[22,23] in similar oxi-
dations, even a 5.0 molar excess of oxidant has been employed
to drive the reaction to completion. Thus the excess amount of
PCC (3.0 equivalents) used in the current protocol is offset by
the reasonably high yields obtained at the end of the process.
The synthetic scope of this transformation is depicted inTable 1,
and it is evident that the reaction tolerates functional variations
around the DHPM core (C4, C5, C6), which is an additional
advantage.
The completion of the reaction and formation of the products
1
could be monitored by using H NMR (CDCl3) spectroscopy
by the shift in the C6 methyl resonance in the products. The
intense singlet of the protons of the C6 methyl group resonates
around δ 2.46–2.71, whereas the corresponding protons in the
precursor DHPMs 2 resonate upfield (δ 2.22–2.37, ꢀδ 0.20–
0.45). Likewise, the disappearance of splitting of the C4-alkyl
substituents in 3, and the disappearance of the doublet of H4 in
the case of C4 aryl substituted DHPMs, offered an unambiguous
monitoring of the reaction progress for the optimization of the
reaction times.
The mechanism of dehydrogenation mediated by PCC is not
certain, as the precise nature of the reduced chromium product
has not been investigated,[21] presumably it is chromium dio-
xide (Cr4+) or some other intermediate formed from chromium
dioxide and pyridinium chloride. It might involve a two-electron
transfer process as proposed in Scheme 2.
PCC adsorbed on a solid support (alumina, silica gel, or
montmorillonite K-10 clay) is remarkably efficient in oxidizing
1,4-DHPs to the corresponding pyridines.[13] During optimiza-
tion of the reaction conditions for the oxidation of 2, when PCC
was supported on these solid supports, and used in dehydrogena-
tion experiments, the reactions neither proceeded to completion
nor did the process offer any operational advantage, thus PCC
Conclusions
We have shown that DHPMs can be efficaciously dehydro-
genated using PCC at the key diversity oriented C4–N3 position
to obtain pyrimidine-2(1H)-ones in a synthetically useful man-
ner. This method has operational advantages such as clean
reaction profiles and simple experimental/product isolation pro-
cedures, which make it a useful and attractive strategy for the
dehydrogenation of DHPMs to obtain pyrimidine-2(1H)-ones of
synthetic importance.
Experimental
General
All compounds were characterized by 1H NMR, 13C NMR, mass
spectrometry (MS), and elemental analysis. NMR spectra were
recorded on a JEOL FT-NMRAL-300 MHz using CDCl3 and/or
(D6)DMSO as solvents and tetramethylsilane as an internal stan-
dard, chemical shifts are given in δ. MS were recorded on a
Bruker Esquire 3000 instrument. Elemental analyses (C, H, N)

912
K. Singh and K. Singh
were performed on a Thermo Flash EA112. Melting points were
recorded in open capillaries and are uncorrected.
4-(4-Methoxyphenyl)-6-methyl-2-oxo-
1,2-dihydropyrimidine-5-carboxylic
Acid Ethyl Ester 3f
Yield (300 mg, 60%). RF (ethyl acetate) 0.3, mp 153–155◦C.
(Found: C 61.7, H 5.7, N 9.5. C15H16N2O4 requires C 62.5, H
5.6, N 9.7%). δH (CDCl3) 7.60 (2H, d, J 8.1, ArH), 6.94 (2H,
d, J 8.4, ArH), 5.36 (1H, br, NH, exch. with D2O), 4.12 (2H, q,
CH2CH3), 3.85 (s, 3H, OCH3), 2.56 (3H, s, CH3), 1.05 (3H, t,
J 6.9, CH2CH3). δC (CDCl3) 166.57, 162.05, 130.08, 127.82,
113.80, 61.61, 55.37, 13.65. m/z 311 [M+].
General Procedure for the Oxidation of
3,4-Dihydropyrimidin-2(1H)-ones 2
A solution of DHPM 2 (0.5 g, 1.97 mmol) (Scheme 1) in CH2Cl2
was stirred with PCC (1.3 g, 5.90 mmol, Aldrich) until the reac-
tion was complete (16–25 h, TLC). The reaction mixture was
filtered over Celite to remove any suspension, and the residue
obtainedafterremovalofthesolventwasflash-chromatographed
to obtain the corresponding pyrimidinone 3.
1,6-Dimethyl-4-(4-nitrophenyl)-2-oxo-
1,2-dihydropyrimidine-5-carboxylic
Acid Ethyl Ester 3g
6-Methyl-2-oxo-1,2-dihydropyrimidine-5-carboxylic
Acid Ethyl Ester 3a
Yield (300 mg, 60%). RF (ethyl acetate) 0.5, mp 128–130◦C.
(Found: C 56.1, H 4.6, N 13.3. C15H15N3O5 requires C 56. 8, H
4.7, N 13.3%). δH (CDCl3) 8.27 (2H, d, J 8.7, ArH), 7.75 (2H,
d, J 8.7, ArH), 4.03 (2H, q, CH2CH3), 3.69 (3H, s, NCH3), 2.61
(3H, s, CH3), 0.93 (3H, t, J 7.2, CH2CH3). δC (CDCl3) 169.05,
166.01, 160.10, 155.25, 148.72, 144.31, 128.81, 123.40, 111.14,
61.95, 33.36, 18.24, 13.44. m/z 340 [M+].
Yield (390 mg, 79%). RF (ethyl acetate) 0.2, mp 210–215◦C.
(Found: C 52.4, H 5.2, N 15.8. C8H10N2O3 requires C 52.8, H
5.5, N 15.4%). δH ((D6)DMSO) 8.69 (1H, s, CH), 5.69 (1H, s,
NH, exch. with D2O), 4.17 (2H, q, CH2CH3), 2.46 (3H, s, CH3),
1.23 (3H, t, J 7.2, CH2CH3). δC ((D6)DMSO) 182.64, 163.62,
106.44, 60.63, 14.19. m/z 205 [M+].
1,6-Dimethyl-2-oxo-1,2-dihydropyrimidine-5-carboxylic
Acid Ethyl Ester 3b
6-Methyl-2-oxo-4-(3,4,5-trimethoxyphenyl)-
1,2-dihydropyrimidine-5-carboxylic
Acid Ethyl Ester 3h
Yield (310 mg, 63%). RF (ethyl acetate) 0.3, mp 130–132◦C.
(Found: C 54.4, H 6.2, N 14.4. C9H12N2O3 requires C 55.1,
H 6.1, N 14.3%). δH (CDCl3) 8.35 (1H, s, CH), 4.25 (2H,
q, CH2CH3), 3.55 (3H, s, NCH3), 2.63 (3H, s, CH3), 1.30
(3H, t, J 7.2, CH2CH3). δC (CDCl3) 176.59, 163.15, 154.99,
152.69, 108.12, 61.17, 48.46, 39.07, 30.85, 26.04, 23.0, 14.19.
m/z 219 [M+].
Yield (300 mg, 60%). RF (ethyl acetate) 0.2. (Found: C 57.9, H
5.0, N 9.1. C17H20N2O6 requires C 57.6, H 5.7, N 8.0%). δH
(CDCl3) 6.80 (2H, s, ArH) 5.23 (1H, s, NH, exch. with D2O),
4.03 (2H, q, CH2CH3), 3.82 (9H, s, OCH3), 2.52 (3H, s, CH3),
0.96 (3H, t, J 7.2, CH2CH3). δC (CDCl3) 166.40, 158.59, 153.14,
140.44, 111.65, 105.43, 61.79, 60.94, 56.23, 8.20. m/z 371 [M+].
6-Methyl-2-oxo-4-phenyl-1,2-dihydropyrimidine-
5-carboxylic Acid Ethyl Ester 3c
6-Methyl-4-(3-nitro-phenyl)-2-oxo-1,2-dihydropyrimidine-
5-carboxylic Acid Isopropyl Ester 3i
Yield (310 mg, 63%). RF (ethyl acetate) 0.4, mp 175–178◦C.
(Found: C 65.4, H 5.6, N 11.0. C14H14N2O3 requires C 65.1,
H 5.4, N 10.9%). δH (CDCl3) 7.40–7.61 (5H, m, ArH), 4.05
(2H, q, CH2CH3), 2.61 (3H, s, CH3), 1.25 (1H, s, OH, exch.
with D2O), 0.938 (3H, t, J 6.9, CH2CH3). δC (CDCl3) 166.09,
158.31, 130.80, 128.36, 127.99, 111.49, 61.60, 45.52, 13.42,
6.28. m/z 281 [M+].
Yield (270 mg, 55%). RF (ethyl acetate) 0.4, mp 203–205◦C.
(Found: C 56.1, H 5.1, N 13.2. C15H15N3O5 requires C 56.8, H
4.7, N 13.3%). δH (CDCl3) 13.75 (1H, br, OH, exch. with D2O),
8.47 (1H, s, ArH), 8.35 (1H, d, J 7.8, ArH), 7.79 (1H, d, J 8.7,
ArH), 7.64 (1H, t, J 7.8, ArH), 5.03 (IH, m, CH(CH3)2), 2.67
(3H, s, CH3), 1.08 (6H, d, J 6.3, CH(CH3)2). δC (CDCl3) 164.60,
158.06, 147.92, 134.03, 129.47, 125.13, 123.21, 111.67, 70.20,
21.29, 18.35. m/z 356 [M+].
1,6-Dimethyl-2-oxo-4-phenyl-1,2-dihydropyrimidine-
5-carboxylic Acid Ethyl Ester 3d
4,6-Dimethyl-2-oxo-1,2-dihydropyrimidine-5-carboxylic
Acid Ethyl Ester 3j
Yield (300 mg, 60%). RF (ethyl acetate) 0.5, mp 116–118◦C.
(Found: C 66.9, H 5.6, N 10.5. C15H16N2O3 requires C 66.2,
H 5.9, N 10.3%). δH (CDCl3) 7.37–7.60 (5H, m, ArH), 4.00
(2H, q, CH2CH3), 3.65 (3H, s, NCH3), 2.55 (3H, s, CH3), 0.87
(3H, t, J 6.9, CH2CH3). δC (CDCl3) 166.90, 158.59, 148.27,
138.24, 130.35, 127.95, 111.56, 61.70, 33.04, 17.99, 13.27. m/z
295 [M+].
Yield (340 mg, 69%). RF (ethyl acetate) 0.2, mp 134–136◦C.
(Found: C 54.5, H 6.6, N 15.0. C9H12N2O3 requires C 55.1, H
6.2, N 14.3%). δH (CDCl3) 5.43 (1H, br, NH, exch. with D2O),
4.36 (2H, q, CH2CH3), 2.56 (6H, s, 2CH3), 1.38 (3H, t, J 7.2,
CH2CH3). δC (CDCl3) 165.26, 158.01, 111.19, 61.52, 14.12.
m/z 219 [M+].
6-Methyl-2-oxo-4-phenyl-1,2-dihydropyrimidine-
5-carboxylic Acid Methyl Ester 3e
4,6-Dimethyl-2-oxo-1,2-dihydropyrimidine-5-carboxylic
Yield (350 mg, 71%). RF (ethyl acetate) 0.2, mp 195–197◦C.
(Found: C 63.1, H 5.2, N 10.7. C13H12N2O3 requires C 63.9, H
4.9, N 11.5%). δH (CDCl3) 13.5 (1H, br, OH, exch. with D2O),
7.41–7.61 (5H, m, ArH), 3.58 (3H, s, OCH3), 2.61 (3H, s, CH3).
δC (CDCl3) 196.59, 130.98, 128.42, 127.97, 96.43, 52.28. m/z
267 [M+].
Acid Methyl Ester 3k
Yield (320 mg, 65%). RF (ethyl acetate) 0.2, mp 160–162◦C.
(Found: C 52.1, H 5.4, N 15.9. C8H10N2O3 requires C 52.7, H
5.5, N 15.4%). δH (CDCl3) 13.53 (1H, br, OH, exch. with D2O),
3.89 (3H, s, OCH3), 2.56 (6H, s, 2CH3). δC (CDCl3) 165.72,
158.10, 110.96, 52.24, 20.77. m/z 205 [M+].

Oxidation of 3,4-Dihydropyrimidin-2(1H)-ones using PCC
913
2-Oxo-4-phenyl-6-propyl-1,2-dihydropyrimidine-
5-carboxylic Acid Ethyl Ester 3l
[5] B. Loev, K. Snader, J. Org. Chem. 1965, 30, 1914. doi:10.1021/
JO01017A048
[6] (a) J. J. Vanden Eynde, R. D’Orazio, Y. Van Haverbeke, Tetrahedron
1994, 50, 2479. doi:10.1016/S0040-4020(01)86964-7
(b) A. Kamal, M. Ahmad, N. Mohd, A. M. Hamid, Bull. Chem. Soc.
Jpn. 1964, 37, 610. doi:10.1246/BCSJ.37.610
Yield (350 mg, 70%). RF (ethyl acetate) 0.6, mp 143–145◦C.
(Found: C 66.9, H 6.9, N 10.2. C16H18N2O3 requires C 67.1, H
6.3, N 9.8%). δH (CDCl3) 8.12 (1H, s, NH, exch. with D2O),
7.40–7.61 (5H, m, ArH), 4.03 (2H, q, CH2CH3), 2.85 (2H, t, J
7.2, CH2CH2), 1.82 (2H, m, CH3CH2CH2), 1.03 (3H, t, J 7.2,
CH3CH2), 0.93 (t, 3H, J 7.2, CH3CH2). δC (CDCl3) 179.65,
166.21, 158.25, 130.68, 128.55, 126.58, 111.30, 101.03, 61.56,
29.62, 22.43, 13.66. m/z 309 [M+].
[7] (a) C. P. Sar, O. H. Hankovszky, G. Jerkovich, I. Pallagi, K. Hideg,
ACH-Models Chem. 1994, 131, 363.
(b) J. J. Vanden Eynde, F. Delfosse, A. Mayence, Y. Van Haverbeke,
Tetrahedron 1995, 51, 6511. doi:10.1016/0040-4020(95)00318-3
(c) A. J. Fatiadi, Synthesis 1976, 133. doi:10.1055/S-1976-23979
(d) O. H. Hankovszky, C. P. Sar, K. Hideg, G. Jerkovich, Synthesis
1991, 91. doi:10.1055/S-1991-26389
4-Methyl-2-oxo-6-phenyl-1,2-dihydropyrimidine-
5-carboxylic Acid Ethyl Ester 3m
[8] D. Walker, J. D. Hiebert, Chem. Rev. 1967, 67, 153. doi:10.1021/
CR60246A002
Yield (355 mg, 71%). RF (ethyl acetate) 0.5, mp 183–185◦C.
(Found: C 65.1, H 5.9, N 11.0. C14H14N2O3 requires C 65.1,
H 5.4, N 10.9%). δH (CDCl3) 13.63 (1H, br, OH, exch. with
D2O), 7.40–7.61 (5H, m, ArH), 4.05 (2H, q, CH3CH2), 2.62
(3H, s, CH3), 0.937 (3H, t, J 7.2, CH3CH2). δC (CDCl3) 166.05,
158.30, 130.76, 128.14, 111.45, 61.57, 13.39. m/z 281 [M+].
[9] (a) J. J. Vanden Eynde, N. Audiart, V. Canonne, S. Michel, Y. Van
Haverbeke, C. O. Kappe, Heterocycles 1997, 45, 1967.
(b) J. J. Vanden Eynde, N. Labuche, Y. van Haverbeke, L. T. Vanden,
Arkivoc 2003, 22.
[10] K. Yamamoto, Y. G. Chen, F. G. Buono, Org. Lett. 2005, 7, 4673.
doi:10.1021/OL051879W
[11] A. Dondoni, A. Massi, E. Minghini, S. Sabbatini, V. Bertolasi, J. Org.
Chem. 2003, 68, 6172. doi:10.1021/JO0342830
[12] H. R. Memarian, A. Farhadi, Ultrason. Sonochem. 2008, 15, 1015.
doi:10.1016/J.ULTSONCH.2008.02.014
6-Methyl-2-oxo-4-pentyl-1,2-dihydropyrimidine-
5-carboxylic Acid Ethyl Ester 3n
[13] J. J. Vanden Eynde, A. Mayaence, A. Maquestiau, Tetrahedron 1992,
48, 463. doi:10.1016/S0040-4020(01)89008-6
[14] P. Shanmugam, P. T. Perumal, Tetrahedron 2007, 63, 666.
doi:10.1016/J.TET.2006.11.010
[15] K. Singh, S. Singh, A. Mahajan, J. Org. Chem. 2005, 70, 6114.
doi:10.1021/JO050675Q
[16] K. Singh, S. Singh, Tetrahedron Lett. 2006, 47, 8143. doi:10.1016/
J.TETLET.2006.09.039
Yield (320 mg, 62%). RF (ethyl acetate) 0.4. (Found: C 60.2,
H 7.1, N 10.8. C13H20N2O3 requires C 61.9, H 7.9, N
11.1%). δH (CDCl3) 4.29 (2H, q, CH2CH3), 2.73 (2H, t, J 7.5,
CH2(CH2)3CH3), 2.45 (3H, s, CH3), 2.10 (1H, s, OH, exch.
with D2O), 1.29 (9H, m, CH2(CH2)3CH3), 0.82 (3H, t, J 6.9,
CH2CH3). δC (CDCl3) 61.67, 31.55, 22.34, 14.12, 13.86, 0.98.
m/z 275 [M+].
[17] K. Singh, D. Arora, S. Singh, Tetrahedron Lett. 2007, 48, 1349.
doi:10.1016/J.TETLET.2006.12.111
Acknowledgements
[18] C. O. Kappe, A. Stadler, Org. React. 2004, 63, 1.
[19] Such DHPMs has been reported to be quite stable towards PCC, see:
A. Puchala, F. Belaj, J. Bergman, C. O. Kappe, J. Heterocycl. Chem.
2001, 38, 1345.
[20] The application of PCC is limited to oxidation of alcohols mainly,
see: G. Piancatelli, A. Screttri, M. D’Auria, Synthesis 1982, 245.
doi:10.1055/S-1982-29766
We thank the UGC (31-53/2005/SR) and CSIR (01(1960)/04/EMR-II),
New Delhi, for financial assistance.
References
[1] C. O. Kappe, Eur. J. Med. Chem. 2000, 35, 1043andreferencestherein.
doi:10.1016/S0223-5234(00)01189-2
[2] (a) D. J. Triggle, in New Perspectives on Calcium Antagonists (Ed.
G. B. Weiss) 1981 (American Physiological Society: Bethesda, MD).
(b) A. Fleckenstein, Annu. Rev. Pharmacol. Toxicol. 1977, 17, 149.
doi:10.1146/ANNUREV.PA.17.040177.001053
[3] R. H. Boecker, F. P. Guengerich, J. Med. Chem. 1986, 29, 1596.
doi:10.1021/JM00159A007
[21] H. C. Brown, C. G. Rao, S. U. Kulkarni, J. Org. Chem. 1979, 44, 2809.
doi:10.1021/JO01329A051
[22] L.A. Beihoffer, R.A. Craven, K. S. Knight, C. R. Sisson,T. G.Waddell,
Trans. Met. Chem. 2005, 30, 582. doi:10.1007/S11243-005-4049-8
[23] P. Shanmugam, P. T. Perumal, Tetrahedron 2006, 62, 9726.
doi:10.1016/J.TET.2006.07.063
[4] J. R. Pfister, Synthesis 1990, 689. doi:10.1055/S-1990-26982