This document describes a novel method for synthesizing highly functionalized 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) through 1,4-addition of nucleophiles onto pyrimidin-2(1H)-ones. Ceric ammonium nitrate (CAN) is used as a catalyst to promote the 1,4-addition reaction of indoles and other nucleophiles with pyrimidin-2(1H)-ones to form novel DHPMs in good yields. A variety of substituted indoles undergo regioselective 1,4-addition to form functionalized 4-indolyl-DHPMs. Pyrrole and sodium boroh
Synthesis, Characterization and Study of Antioxidant Activities of Some New P...IJRES Journal
A series of substituted pyrazoline derivatives 5(a-c) have been synthesized by the reaction of substituted chalcones 4(a-c) with isatinhydrazide. The starting materials, chalcones were prepared by clasien schimidt condensation of appropriate 1-hydroxy-2-acetonaphthone with substituted aldehydes in the presence of sodium hydroxide and in poly ethylene glycol (PEG-400). The structures of the synthesized compounds were confirmed by IR, 1HNMR & Mass spectral data. The synthesized compounds were screened for Antioxidant Activity by DPPH method.
Synthesis, characterization, in vitro cytotoxic and antioxidant activities of...ijperSS
ABSTRACT
A series of novel (Z)-3-(2-(4-(2-oxo-2H-chromen-3-yl) thiazol-2-yl-)hydrazono)indolin-2-one (8a-8d, 9) were synthesized with various substituted indole derivatives. Structures of the newly synthesized compounds were elucidated by FT-IR, 1H-NMR, 13C-NMR and API-ES Mass spectral data. The in vitro cytotoxic activities of the complexes measurement against the human cancer T-lymphocyte cell lines. In vitro evaluation of these title complexes revealed cytotoxicity from 6.8-18µg/mL against CEM, 9.2-21µg/mL against L1210, 10-19µg/mL against Molt4/C8, 8-12µg/mL against HL60 and 8-16µg/mL against BEL7402. Coumarin derivatives 8c and 8d showed that quite significant anticancer activities. The antioxidant activity of the synthesized compounds was evaluated by DPPH scavenging method. Compounds 8c, 8d and 9 showed significant antioxidant activity compared with that of standard drug, ascorbic acid.
Key words: Coumarin, DPPH, Cytotoxic activity.
Synthesis, Characterization and Study of Antioxidant Activities of Some New P...IJRES Journal
A series of substituted pyrazoline derivatives 5(a-c) have been synthesized by the reaction of substituted chalcones 4(a-c) with isatinhydrazide. The starting materials, chalcones were prepared by clasien schimidt condensation of appropriate 1-hydroxy-2-acetonaphthone with substituted aldehydes in the presence of sodium hydroxide and in poly ethylene glycol (PEG-400). The structures of the synthesized compounds were confirmed by IR, 1HNMR & Mass spectral data. The synthesized compounds were screened for Antioxidant Activity by DPPH method.
Synthesis, characterization, in vitro cytotoxic and antioxidant activities of...ijperSS
ABSTRACT
A series of novel (Z)-3-(2-(4-(2-oxo-2H-chromen-3-yl) thiazol-2-yl-)hydrazono)indolin-2-one (8a-8d, 9) were synthesized with various substituted indole derivatives. Structures of the newly synthesized compounds were elucidated by FT-IR, 1H-NMR, 13C-NMR and API-ES Mass spectral data. The in vitro cytotoxic activities of the complexes measurement against the human cancer T-lymphocyte cell lines. In vitro evaluation of these title complexes revealed cytotoxicity from 6.8-18µg/mL against CEM, 9.2-21µg/mL against L1210, 10-19µg/mL against Molt4/C8, 8-12µg/mL against HL60 and 8-16µg/mL against BEL7402. Coumarin derivatives 8c and 8d showed that quite significant anticancer activities. The antioxidant activity of the synthesized compounds was evaluated by DPPH scavenging method. Compounds 8c, 8d and 9 showed significant antioxidant activity compared with that of standard drug, ascorbic acid.
Key words: Coumarin, DPPH, Cytotoxic activity.
Synthesis and Characterization of Schiff Base from Aromatic Amine and Aromati...ijtsrd
The synthesis of Schiff base From Aromatic Amine And Aromatic P Nitro benzaldehyde was performed by a novel method of stirring followed by the addition of p nitro benzaldehydeandm nitro aniline 0.02M . Characterization of the synthesized compounds, determination of purity and identity of the compounds using following spectroscopic and chromatographic techniques Solubility, Thin Layer Chromatographic studies, Ultra Violet studied rotational and vibrational studies FT IR studies. The compounds were investigated for their Antimicrobial activity by cup plate method. Compound1 nitro 4 1 imino,4 nitrophenyl benzene was found to be the most active according to pharmacological evaluation exhibited antimicrobial. Ms. Chetana D. Patil | Mr. Digamber N. Bhosale | Ms. Smita P. Bedis "Synthesis and Characterization of Schiff Base from Aromatic Amine and Aromatic P-Nitro Benzaldehyde" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-5 , August 2019, URL: https://www.ijtsrd.com/papers/ijtsrd26401.pdfPaper URL: https://www.ijtsrd.com/pharmacy/medicinal-chemistry/26401/synthesis-and-characterization-of-schiff-base-from-aromatic-amine-and-aromatic-p-nitro-benzaldehyde/ms-chetana-d-patil
Mechanistic Aspects of Oxidation of P-Bromoacetophen one by Hexacyanoferrate ...IJERA Editor
The kinetics of oxidation of p-bromoacetophenone by hexacyanoferrate (III) has been studied in alkaline
medium. The order of reaction with respect of both acetophenone and hexacynoferrate (III) has been found to be
unity. The rate of reaction increases with increase in the concentration of sodium hydroxide.On addition of
neutral KCl, reaction rate increases. The effects of solvent and temperature have been also studied. The product
p-bromophenyl glyoxal have been characterized by IR studies.
Simple Synthesis of Some Novel Polyfunctionally Derivatives of 2H-Coumarin-2-...IOSRJAC
Compound (2) was prepared from the reaction of ethyl-2-oxo-2H-coumarin-3-carboxylate (1) with ethylcyanoacetate in ethanol containing a catalytic amount of piperidine as catalyst. Compound (2) is the key intermediate for the synthesis of several series of new compounds such as ((pyrimidine, tetrazine, piperidine, oxazepine)-2H-coumarin-2-one derivatives by reaction with selected reagents such as urea, cyanoacetamide, cyanoacetohydrazide, orthoaminophenol and 5-aminotriazole.
Syntheses and Characterizations of Some New N-alkyl, Isoxazole and Dioxazole ...IJAEMSJORNAL
N-alkyl and cycloadducts derivatives of 5-Chloroisatin were synthesized in good to excellent yields. The method evidences a selective N-alkylation when using 1,2-bis (2-chloroethoxy) ethane as efficient spacer at room temperature on the 5-Chloroisatin moiety. A general method for the 1,3-dipolar cycloaddition of 4-Chlorobenzaldoxime to alkynes provides a useful alternative route to get newisoxazole et dioxazole derivatives.
Synthesis, characterization and antimicrobial evaluation of novel diethyl (2-...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Synthesis and Characterization of Schiff Base from Aromatic Amine and Aromati...ijtsrd
The synthesis of Schiff base From Aromatic Amine And Aromatic P Nitro benzaldehyde was performed by a novel method of stirring followed by the addition of p nitro benzaldehydeandm nitro aniline 0.02M . Characterization of the synthesized compounds, determination of purity and identity of the compounds using following spectroscopic and chromatographic techniques Solubility, Thin Layer Chromatographic studies, Ultra Violet studied rotational and vibrational studies FT IR studies. The compounds were investigated for their Antimicrobial activity by cup plate method. Compound1 nitro 4 1 imino,4 nitrophenyl benzene was found to be the most active according to pharmacological evaluation exhibited antimicrobial. Ms. Chetana D. Patil | Mr. Digamber N. Bhosale | Ms. Smita P. Bedis "Synthesis and Characterization of Schiff Base from Aromatic Amine and Aromatic P-Nitro Benzaldehyde" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-5 , August 2019, URL: https://www.ijtsrd.com/papers/ijtsrd26401.pdfPaper URL: https://www.ijtsrd.com/pharmacy/medicinal-chemistry/26401/synthesis-and-characterization-of-schiff-base-from-aromatic-amine-and-aromatic-p-nitro-benzaldehyde/ms-chetana-d-patil
Mechanistic Aspects of Oxidation of P-Bromoacetophen one by Hexacyanoferrate ...IJERA Editor
The kinetics of oxidation of p-bromoacetophenone by hexacyanoferrate (III) has been studied in alkaline
medium. The order of reaction with respect of both acetophenone and hexacynoferrate (III) has been found to be
unity. The rate of reaction increases with increase in the concentration of sodium hydroxide.On addition of
neutral KCl, reaction rate increases. The effects of solvent and temperature have been also studied. The product
p-bromophenyl glyoxal have been characterized by IR studies.
Simple Synthesis of Some Novel Polyfunctionally Derivatives of 2H-Coumarin-2-...IOSRJAC
Compound (2) was prepared from the reaction of ethyl-2-oxo-2H-coumarin-3-carboxylate (1) with ethylcyanoacetate in ethanol containing a catalytic amount of piperidine as catalyst. Compound (2) is the key intermediate for the synthesis of several series of new compounds such as ((pyrimidine, tetrazine, piperidine, oxazepine)-2H-coumarin-2-one derivatives by reaction with selected reagents such as urea, cyanoacetamide, cyanoacetohydrazide, orthoaminophenol and 5-aminotriazole.
Syntheses and Characterizations of Some New N-alkyl, Isoxazole and Dioxazole ...IJAEMSJORNAL
N-alkyl and cycloadducts derivatives of 5-Chloroisatin were synthesized in good to excellent yields. The method evidences a selective N-alkylation when using 1,2-bis (2-chloroethoxy) ethane as efficient spacer at room temperature on the 5-Chloroisatin moiety. A general method for the 1,3-dipolar cycloaddition of 4-Chlorobenzaldoxime to alkynes provides a useful alternative route to get newisoxazole et dioxazole derivatives.
Synthesis, characterization and antimicrobial evaluation of novel diethyl (2-...iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
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A series of novel 5-[2-(4-fluorobenzyl)-6-aryl-imidazo[2,1-b][1,3,4]thiadiazol-5-ylmethylene] thiazolidine-2,4-dione derivatives (4a-d) were synthesized. These final compounds (4a-d) were synthesized by Knoevenagel condensation of 2-(4-fluorobenzyl)-6-arylimidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehydes (3a-d) with thiazolidine-2,4-dione. All the newly synthesized compounds were screened for their invivo hypoglycemic and hypolipidemic activity in male Wister rats. The Structures of all the newly synthesized compounds were established by analytical and spectral data.
Oxidation of 7-Methyl Sulfanyl-5-Oxo-5H-Benzothiazolo-[3, 2-A]-Pyrimidine-6-...inventionjournals
International Journal of Engineering and Science Invention (IJESI) is an international journal intended for professionals and researchers in all fields of computer science and electronics. IJESI publishes research articles and reviews within the whole field Engineering Science and Technology, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
Synthesis And Antibacterial Activity Of 3-[(3-Phenyl-5-Thioxo-1, 5-Dihydro-4h...inventionjournals
A series of 3-[(3-phenyl-5-thioxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)imino]-1,3-dihydro-2Hindole-2-one derivatives were synthesised through the nucleophilic substitution at carbonyl carbon of Isatin. Structure of synthesized compounds were elucidated by using IR, 1H NMR & 13C NMR spectrometry. Synthesised compounds showed significant antibacterial activity against E.coli (ATCC 35218), S.aureus (ATCC 25323), E.faecalis (Clinical isolate), K. Pneumonia, P. aeruginosa (ATCC 27893) using agar well diffusion method.
Facial and Simple Synthesis of Some New (Pyrazole and Triazole) Coumarin Deri...IOSRJAC
2-oxo-2H-coumarin-3-carbohydrazide (2) which prepared from the reaction of ethyl-2-oxo-2Hcoumarin-3-carboxylate (1) with hydrazine hydrate in ethanol containing a catalytic amount of piperidine mixture consider a good and available starting intermediate for synthesis of series of functionalized coumarins. So, compound (2) was utilized as a key for the synthesis of some new (pyrazole, triazole)-2H- coumarin-2-one derivatives by the reaction with some selected reagents.
Anthranilic acid on heating with a primary amide
resulted in benzamidomethyl/ phthalimidomethyl-quinazolin 4
(3H) ones (II) which on treatment with phosphorus oxychloride
(POCl3) and phosphorus pentachloride (PCl5) afforded 4-chloro-
2-benzamidomethyl/phthalimidomethyl-quinazolines (III).
Reaction of (III) with o-phenylenediamine in anhydrous pyridine
furnished 2-benzamidomethyl/ phthalimido-methylbenzimidazolo
[2, 1-c] quinazolines (IV). A part of synthetic
strategy was also adopted for the synthesis of 2-
benzamidomethyl/ phthalimidomethyl-tetrazolo [1, 5-c]
quinazolines (V) with the interaction of (III) with sodium azide
(NaN3) indimethyl sulphoxide (DMSO) solvent (Scheme)
Synthesis of 3-methoxy-6-phenyl-6, 6a-dihydro-[1] benzopyrano-[3, 4-b] [1] be...IOSR Journals
Abstract: The 3-methoxy-6-phenyl-6,6a-dihydro-[1]benzopyrano-[3,4-b][1]benzopyran has been synthesised according to eight-steps synthesis. The target compound was obtained using a synthetic route based on two key cyclisations steps including the platinum chlorides-catalysed of alkynones and intramolecular oxo-Michael addition.
An efficient synthesis, characterization and antibacterial activity of novel ...iosrjce
IOSR Journal of Applied Chemistry (IOSR-JAC) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of applied chemistry and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Chemical Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
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1. A novel method for the synthesis of highly functionalized
3,4-dihydropyrimidin-2(1H)-ones through the 1,4-addition
on pyrimidin-2(1H)-ones
P. Shanmugam,a
P. Boobalanb
and P. T. Perumala,*
a
Organic Chemistry Division, Central Leather Research Institute, Sardar Patel Road, Adyar, Chennai 600 020, Tamilnadu, India
b
Department of Chemistry, Virginia Tech., VA 24060, USA
Received 7 April 2007; revised 6 September 2007; accepted 20 September 2007
Available online 29 September 2007
Abstract—A novel method for synthesizing hitherto unreported 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) through 1,4-addition of nucleo-
philes on pyrimidin-2(1H)-ones is disclosed herein.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
The synthesis of Biginelli compounds has attracted attention
for more than a decade.1
The interest in DHPM synthesis is
not only due to its structural similarity with the well-known
Hantzsch dihydropyridine (calcium channel modulators) but
also to their various medicinal and biological applications.2,3
DHPM synthesis involves either the one-pot coupling of
ethyl acetoacetate, urea and an aldehyde4
or the reaction
of protected urea with enones.5
Most methods including
combinatorial chemistry approaches have exploited com-
mercially available aldehydes or 1,3-dicarbonyl compounds
(the most varied components) to synthesize DHPMs.6,7
We have shown that the cardiotonic activities of 4a–e are
better than Digoxin8
which inspired us to synthesize highly
functionalized DHPMs to further improve the activity. How-
ever, the synthesis of DHPM scaffolds with strictly defined
substitution patterns is often difficult due to the lack of start-
ing materials and lower yields of one-pot condensations
involving structurally complex building blocks.1e,9
2. Results and discussion
2.1. Synthesis of highly functionalized DHPMs
We recently disclosed a novel method for the synthesis of
6-unsubstituted pyrimidin-2(1H)-ones 5 by Co2+
/S2O8
2À
me-
diated oxidation of 4 (Scheme 1).10
a,b-Unsaturated conju-
gated systems of 5a–e were expected to act as Michael
acceptors. Therefore 1,4-addition of (substituted)indole,
pyrrole, phenol, electron-rich imine, azide and hydride can
be expected to yield hitherto unreported DHPMs (Scheme
2). Metal ions (Ni2+
, Cu+
, Fe3+
, Ce4+
or In3+
) were proven
to be more effective for inter- and intramolecular Michael
addition reactions.11–13
In our method, InCl3, FeCl3 and
ceric ammonium nitrate (CAN) were screened initially for
catalytic activity. We found that CAN promoted reactions
were clean and afforded higher yields of product.
For an illustrative example, 5a in anhydrous methanol was
stirred with indole at ambient temperature under argon at-
mosphere. To the stirring reaction mixture was added
5 mol % of CAN and the total consumption of 5a after an
hour as monitored by TLC was an indication of completion
of the reaction (Scheme 2). However, the reaction when
conducted without the addition of CAN did not afford any
appreciable amount of 6a.
The 1
H NMR spectrum of 6a showed a doublet with J¼3 Hz
at d 5.54 ppm. This is attributed to the CH group adjoining
the NH group, which is commonly observed in DHPM
chemistry.6b,14
The 13
C NMR spectrum of 6a had absorp-
tions around d 48 and 101 ppm (respectively for CH(4)
and C(5)) confirming the formation of 1,4-addition product.
The product formation was further ascertained by mass
N
NH
Ar
H3C
O
O
R
N
N
Ar
H
O
O
R
R1Co(NO3)2
.6H2O/K2S2O8
4 5
CH3CN/H2O
80 °C
R1
Scheme 1. Unprecedented oxidation of 6-methyl DHPMs (4) by Co3+
.
* Corresponding author. Tel.: +91 44 2491389; fax: +91 44 24911589;
e-mail: ptperumal@gmail.com
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.066
Tetrahedron 63 (2007) 12215–12219
2. spectrum (m/z¼361), IR spectrum (n¼3589, 3370,
3293 cmÀ1
corresponding three NH stretching) and elemen-
tal analysis. The crystallographic data finally confirmed the
structure of the product ascribed to 6a (Fig. 1).15
2.2. Screening of substituted indole addition on 5a–e
The structural and electronic requirements needed for 1,4-ad-
dition on 5a–e by (substituted)indoles were deduced from the
conclusions of the following experiments. (i) Chemoselec-
tive addition on 5a–e by (substituted)indoles yielded exclu-
sively 1,4-addition product. (ii) (Substituted)indoles form
C–C bond on 5a–e regioselectively at C(3) position. (iii)
3-(Substituted)indoles (2-(3-indolyl)ethylamine) or indole
bearing strong electron-withdrawing groups (3-formyl in-
dole, 1-methyl-2-formyl indole, ethyl 2-indole-carboxylate,
2-ethoxycarbonyl-3-methylindole and 5-nitroindole) failed
to afford isolable yields of product. In contrast electron-
donating groups such as a methyl or an ethyl group in indole
increased the yields of the reaction. (iv) (Ethyl 6-methyl-4-
phenyl-pyrimidin-2(1H)-one)-5-carboxylate (C(6)-methyl-
substituted 5a)16
did not undergo 1,4-addition.
The characteristic peaks of 6b–i were similar to X-ray
determined structure of 6a confirming their formation.
Indole bearing moderate electron-withdrawing group or
halogen atom afforded moderate to good yields of DHPMs
(Scheme 3, compounds 6e and 6g). Phenol, resorcinol,
amines (aniline, methylamine and 1-phenylethylamine),
azides, ethyl acetoacetate, imines, N-ethyl carbazole and
N-aryl pyrazole failed to afford corresponding 1,4-addition
products. But pyrrole and hydride (NaBH4) were added
onto 5 under the same conditions to yield novel DHPMs. To
the best of our knowledge, pyrrolyl dihydropyrimidin-2(1H)-
ones and 6-aryl-4-unsubstituted dihydropyrimidin-2(1H)-one
have not been reported in the literature (Scheme 4).
The application of CAN as a catalyst during the addition of
indole on a,b-unsaturated system has also been reported by
Figure 1. ORTEP diagram of 6a.
R1
H3
O
Ar
HO
NH2
NH2O N
H
NHR1
H3
O Ar
N
H
NR1
O
r
H N
H
NH
O
O
Ar
Nu
R1
NH
N OAr
HO
R1
N
H
NHR1
H3
O A
O Ar
H
1
C O C O
C O
2 3
a b
c
4
5a-e 6,7
85-90% 69-84%
69-91%
Scheme 2. Synthesis of highly functionalized DHPMs. (a) Na2SO4,
In(OTf)3 (5 mol %), MW; (b) Co(NO3)2$6H2O/K2S2O8, CH3CN/H2O,
80
C; (c) Nu (2 equiv), Ce(NH4)2(NO3)6 (5 mol %), rt.
NH
N
H
O
O
EtONH
N
H
O
O
EtO NH
N
H
O
O
EtO
NH
NO2
N OAr
HO
R1
Ar
NH
N
H
O
O Nu
R1
5a,5d,5e 7a-c
Ce(NH4)2(NO3)6 (2 mol%)
MeOH, rt
1-3 h
NuH ( 2eq)
7b(71%) 7c(81%)
Nu = Pyrrolyl, H
7a(73%)
3
6
4
3
6
4
NH1
Scheme 4. Synthesis of 4-unsubstituted and 4-pyrrolyl-3,4-DHPMs.
N
NH
N
H
O
O
EtO
N
NH
N
H
O
O
EtO
CH3
NH
N
H
O
O
EtO
CH3
NH
N
H
O
O
H3C
N
NH
N
H
O
O
EtO
NH
N
H
O
O
EtO NH
N
H
O
O
EtO
Br
Cl
NH
N
H
O
O
EtO
CH3
NO2
N
NH
N
H
O
O
EtO
NO2
CH3
Ar
NH
N
H
O
O Nu
R1NH
N OAr
HO
R1
6a(79%) 6b(83%) 6c(91%) 6d(86%)
6e(69%) 6f(86%) 6g(72%)
6h(83%) 6i(87%)
5a-5d
1
3
3
6a-i
Ce(NH4)2(NO3)6 (5 mol%)
MeOH, rt
1-3 h
NuH ( 2 eq)
Nu = (substituted)Indole
6
4
6
4
H N
H
N
H
N
H
N
H
N
H
1
Scheme 3. Highly functionalized 4-indolyl-3,4-DHPM.
12216 P. Shanmugam et al. / Tetrahedron 63 (2007) 12215–12219
3. others.11g
We believe that catalytic amount of CAN would
promote the reaction by coordination with carbonyl group
thereby rendering C-4 position of 5a–e more electrophilic
towards addition. But the mechanistic details of the reaction
were not studied. Catalytic amount of CAN used in the
reaction merely promoted 1,4-addition and did not oxidize
6 and 7.
3. Experimental procedure
3.1. General
Melting points were determined using open capillary tubes
and are reported uncorrected. IR measurements were carried
out using KBr pellets in FTIR spectrometer. The 1
H NMR
and 13
C NMR were recorded in 500 MHz high resolution
NMR spectrometer using TMS as an internal standard. All
NMR spectra of pyrimidin-2(1H)-ones were recorded in
CDCl3. Mass spectra were obtained in EI ionization mode
at 70 eV. TLC analysis was performed using precoated Poly-
Gram sheets. Column chromatography was carried out using
100–200 mesh silica gel or flash-column with 200–400 mesh
silica gel. Acetonitrile was freshly distilled from P2O5 prior
to use. Ceric ammonium nitrate was used as purchased lo-
cally. Indole-3-carboxaldehyde, indium trichloride, indium
triflate and N-methyl indole were purchased from Aldrich
Sigma Chemicals.
All the DHPMs needed for oxidation were prepared using re-
ported procedure and purified through column chromato-
graphy before subjecting to dehydrogenation.6b
3.2. Experimental procedure for the cobalt nitrate
and potassium persulfate mediated oxidation of
3,4-dihydropyrimidin-2(1H)-ones10
A 50 mL round bottom flask containing a magnetic bar was
charged with 1 mmol (0.260 g) of 4a and 10 mL acetonitrile.
To this solution was added a mixture of cobalt(II) nitrate
hexahydrate (5 mmol, 1.46 g) and potassium persulfate
(2.5 mmol, 0.68 g) in 3 mL of water and the solution was
stirred at 80
C (oil bath). The stirring was continued at
80
C for 3 h. TLC showed the complete disappearance of
4a. The reaction mixture was diluted with 20 mL of
CHCl3 and the supernatant was decanted. The residue was
poured into 20 g of crushed ice and extracted with CHCl3
(2Â20 mL). The organic extracts were pooled, washed
with brine solution (2Â20 mL), dried over anhydrous
Na2SO4 and concentrated in vacuum to afford 0.23 g of
crude product. The column purification of residue using
1:1 petroleum ether–ethyl acetate afforded 0.19 g of 5a as
colourless viscous compound, which upon cooling forms
a crystalline solid. The same procedure was employed for
synthesizing 5b–f.
3.3. Synthesis of ethyl 6-methyl-4-phenyl-pyrimidin-
2(1H)-one-5-carboxylate (5f)16
A 50 mL round bottom flask containing a magnetic bar was
charged with 4a (1 mmol, 0.260 g), NaHCO3 (5 mmol,
0.420 g) and 10 mL of acetone. To this suspension was
added CAN (3 mmol, 1.65 g) in water for an hour and stirred
at À5
C under argon atmosphere. The stirring was contin-
ued overnight at room temperature and the reaction mixture
was diluted with CHCl3 (20 mL) and decanted. The residue
was washed with CHCl3 (2Â30 mL). The combined CHCl3
layer was neutralized, washed with NaCl solution
(2Â20 mL), dried over anhydrous Na2SO4 and column chro-
matographed using 1:1 mixture of ethyl acetate–petroleum
ether to afford 0.214 g of 5f.
3.4. Experimental procedure for 1,4-addition of indole
on pyrimidin-2(1H)-ones (6)
3.4.1. Typical procedure for the synthesis of 6a. A 25 mL
round bottom flask containing a magnetic bar was charged
with pyrimidin-2(1H)-one, 5a, (0.150 g, 0.6 mmol) in
5 mL of anhydrous methanol. To this solution was added in-
dole (0.143 g, 1.2 mmol) and the solution was stirred at
room temperature under argon atmosphere. Upon addition
of 5 mol % of CAN, the solution turned to dark brown imme-
diately and stirring was continued for 1–3 h at room temper-
ature. After completion of the reaction (monitored by TLC),
the reaction mixture was poured into 50 mL of water and ex-
tracted with CHCl3 (3Â30 mL). The organic extracts were
pooled, dried over anhydrous Na2SO4 and purified by pass-
ing through a small column of SiO2 using 2:1 petroleum
ether–ethyl acetate to afford 6a.
A similar reaction conducted using FeCl3 was worked up by
adding three to five drops of 6 N HCl (w0.5 mL), extracted
with CHCl3 (3Â30 mL), dried over anhydrous Na2SO4 and
column chromatographed using 2:1 petroleum ether–ethyl
acetate. The InCl3 catalyzed reaction was worked up similar
to the ceric ammonium nitrate procedure.
3.5. General procedure for the reduction of pyrimidin-
2(1H)-ones
3.5.1. Typical procedure for the synthesis of 7a. A 25 mL
round bottom flask containing a magnetic bar was charged
with pyrimidin-2(1H)-one, 5a, (0.150 g, 0.6 mmol) in
5 mL of anhydrous methanol. To this solution was added
indole (0.045 g, 1.2 mmol) and the resulting solution was
stirred at room temperature under an Ar atmosphere.
CAN of 2 mol % was added. The reaction was vigorous
and completed within half an hour (monitored by TLC).
To the reaction mixture, 5 mL of 6 N HCl was added to de-
compose the excess NaBH4 and the reaction mixture was
extracted with CHCl3 (3Â30 mL), dried over anhydrous
Na2SO4 and passed through a small column of SiO2 (1:1
petroleum ether–ethyl acetate) to yield 4-unsubstituted
DHPMs.
3.6. Spectral characterization
3.6.1. Ethyl 6-phenyl-4-(1H-indol-3-yl)-3,4-dihydropyri-
midin-2(1H)-one-5-carboxylate (6a). Colourless solid.
Mp 190–191
C. Rf 0.31 (25% ethyl acetate–petroleum
ether). IR (KBr): 1087, 1241, 1371, 1456, 1659, 1710,
2918, 3077, 3195, 3293, 3370, 3589 cmÀ1
. 1
H NMR:
d 0.67 (t, J¼7.5 Hz, 3H, OCH2CH3), 3.65 (q, J¼7.5 Hz,
2H, OCH2CH3), 5.54 (d, J¼3.1 Hz, 1H, CH(4)), 6.97 (t,
J¼6.9 Hz, 1H), 7.05 (t, J¼6.9 Hz, 1H), 7.17 (d, J¼2.3 Hz,
1H), 7.24 (dd, J¼2.3, 8.4 Hz, 2H), 7.34 (m, 4H), 7.67 (t,
12217P. Shanmugam et al. / Tetrahedron 63 (2007) 12215–12219