Unusual reactivity of 2,3-diphenylcyclopropenone towards N-imidoylthioureas; facile synthesis of 3-aryl-2,5,6-triphenylpyrimidin-4(3H)- one (PART III)

Article abstract of DOI:10.3184/030823407X234563

2,3-Diphenylcyclopropenone (1) reacts with N-imidoylthioureas 2a-e to form the pyrimidin-4(3H)-ones 5a-e. The reaction mechanism can be described as due to stepwise addition accompanied by elimination of phenyl isothiocyanate.

Full text of DOI:10.3184/030823407X234563

JOURNAL OF CHEMICAL RESEARCH 2007
AUGUST, 439–441
RESEARCH PAPER 439
Unusual reactivity of 2,3-diphenylcyclopropenone towards N-imidoyl-
thioureas; facile synthesis of 3-aryl-2,5,6-triphenylpyrimidin-4(3H)-one
(PART III)
Ashraf A. Alya*, Ahmed M. NourEl-Dina, Moshen A.-M. Gomaaa, Alan B. Brownb and
Magda S. Fahmia
aChemistry Department, Faculty of Science, El-Minia University, 61519-El-Minia, A. R. Egypt
bChemistry Department, Florida Institute of Technology, 150 W University Blvd, Melbourne, Florida 32901, USA
2,3-Diphenylcyclopropenone (1) reacts with N-imidoylthioureas 2a–e to form the pyrimidin-4(3H)-ones 5a–e.
The reaction mechanism can be described as due to stepwise addition accompanied by elimination of phenyl
isothiocyanate.
Keywords: N-imidoylthioureas, 2,3-diphenylcyclopropenone, stepwise mechanism, pyrimidin-4-ones
Cyclopropenones undergo several interesting cycloaddition
reactions and they may be useful starting materials for a
variety of compounds.1,2 They are also reactive toward dipolar
reagents and compounds having a reactive π-system.3-5
There is systematic interest in the use of cyclopropenone
chemistry to construct a wide variety of heterocycles.6
Diphenylcyclopropenone (1) has been found to react with a
wide range of imines and other compounds containing the C=N
moiety, usually to form azacyclopentenones (pyrrolinones)
via formal [2 + 3] cycloaddition reactions.7-12 By contrast,
the reaction of 1 with guanidine and its alkyl and/or aryl
derivatives gave the corresponding 5,6-dihydropyrimidin-
4(1H)-ones via a formal [3 + 3] cycloaddition reaction.13
In general, cyclopropenones are strained ring ambident
electrophiles with a tendency to form ring opened products;
their reaction with nucleophiles can involve carbonyl or
conjugate addition.14,15 N-Imidoylthioureas have been shown
limited attention in the field of heterocyclic synthesis.16,17
The synthesis of pyridazinethiones and 1,2,4-triazolo[4,3-
b]pyridazinethiones from the reaction of thiosemicarbazides
with 1 has been described previously.18 Moreover, we have
isolated (E/Z)-3-(aroylthioureido)-2-phenylcinnamates from
the reactions of N-substituted aroylthioureas with 1 in
acetic acid. That abnormal activity was described as due to
3
nucleophilic addition of Nꢀ followed by hydrolysis, ring
opening and oxidation processes.19 It has recently been
reported20 that (E)-N-[2-([2.2]paracyclophan-4-yl)ethylidene]
methylamine-N-oxide reacted with
1 to produce the
corresponding paracylophanyl-pyrrole-2-one. Yoshida21
previously reported that the reaction of N-imidoyl sulfoximides
with 1 at 150°C afforded a mixture of 1,2-disubstituted 5,6-
diphenylpyrimidin-4(1H)-ones and N-(4-oxo-2-pyrrolin-5-yl)
sulfoxoimides. On the other hand, compound 1 reacted with
sulfimides to give predominately pyrimidin-4-ones.22-24 4-
Pyrimidones were also obtained from the reaction of 2,4,5-
triphenyl-3H-pyrrol-3-one 1-oxide with nitrones.25
Results and discussion
In the light of the aforementioned results, our attention turned
to the reactions of 2,3-diphenylcyclopropenone (1) with
Ph
H+
O
Ar
H
N
Ph
Ph
H
O
- H+
1
EtOH
H
N
Ph
S
N
NAr
N
Ph
10-16 h
S
+
Ph
Ph
2a-e
Ph
HN
3a-e
O
O
N
Ar
Ph
Ph
Ar
Ph
Ph
N
H-
N
PhN=C=S
-
Ph
Ph
N
Ph
Ar
5a-e
Yield (%)
N
H
S
2-5
4-OCH3-C6H4-
4-CH3-C6H4-
4-Cl-C6H4-
4-NO2-C6H4-
C6H5-
a
b
c
80
76
70
60
74
4a-e
d
e
Scheme 1 Rationale for the formation and synthesis pyridim-4(3H)-ones 5a–e.
* Correspondent. E-mail: ashraf160@yahoo.com
PAPER: 07/4676

440 JOURNAL OF CHEMICAL RESEARCH 2007
N-imidoylthioureas 2a–e (Scheme 1). We chose N-imidoyl
thioureas 2a–e having aryl groups with electron donating
and withdrawing substituents on the benzene ring, in order
to examine their reactivity which might affect the course of
reaction. The reactions of 2a–e with 1 were carried out in
absolute ethanol at reflux temperature and afforded compounds
5a–e in 60–80% yields together with small amounts of phenyl
isothiocyanateꢀin nearly 5% (Scheme 1). The structure proof
of 5a–e was based upon the mass, 1H NMR, 13C NMR
and IR spectra as well as elemental analyses. For example,
the reaction of compound 1 with 2a, for 10 h, furnished yellow
crystals of 5a in 80% yield (Scheme 1). Mass spectrometry
and elemental analysis proved the molecular formula of 5a as
C29H22N2O2. The IR spectrum did not reveal any absorption
assigned to the presence of NH, CS, or OH groups. However,
a sharp band appeared at n = 1695 cm-1 due to the presence
of a carbonyl group. The aromatic protons resonated in the
1H NMR spectrum of 5a as two double–doublets and two
multiplets, respectively corresponding to the p-methoxyphenyl
group and the other three phenyl groups. The 13C DEPT
aerial oxidation of N-phenylthioformamide (6) occurs26 which
may be catalysed under the reaction conditions (Scheme 1).
This may also explain the low yield of the resulting phenyl
isothiocyanate.
In the last few years, substituted pyrimidinone and
pyrimidinedione derivatives have shown selective antitumor,26
antiviral,27 antitubercular,28 and antifungal activity.29 From the
aforesaid follows the importance of our mode of synthesis,
since the products formed from readily available starting
materials. Moreover, these products can be expected to have
biological and pharmaceutical activities.
Experimental
All melting points were recorded on a Gallenkamp apparatus.
The IR spectra were obtained on Shimadzu 470 spectrophotometer
using potassium bromide pellets. The 1H NMR (400.134 MHz)
and 13C NMR (100.6 MHz) spectra were measured in CDCl3 using
a Bruker AM 400 spectrometer with TMS as an internal standard.
Coupling constants are expressed in Hz. Mass spectra were recorded
on a Finnigan MAT 8430 instrument at 70 eV. Elemental analyses
were carried out in the Microanalysis Centre of the Institut für
Anorganische Chemie, Technische Universität Braunschweig.
For preparative thin layer chromatography (PLC), glass plates
(20 ¥ 48 cm) were covered with a slurry of silica gel Merck PF254
and air-dried using the solvents listed for development. Zones were
detected by quenching of indicator fluorescence upon exposure to
254 nm light; elution of the different bands with toluene afforded the
pure products.
1
135/90 spectrum of 5a supported the H NMR spectroscopic
data by the appearance of the positive amplitude appearance
of only 11 aromatic-CH signals; in eight of them each signal
constitutes two carbons (see the Experimental). Distinctive
signals appeared in the 13C NMR spectrum of 5a at dC 51.0,
124.0, 132.0, 145.9, 150.9, 162.1 and 168.8 corresponding
to OCH3, C-5, N–Ar–C, C-6, OMe–Ar–C, C-2 and C-4,
respectively.
Startingꢀmaterials
In the case of 5d, the 1H NMR spectrum revealed the most
deshielded aromatic protons as two double–doublets at dHꢀ8.10
and 7.80 (Jꢀ= 8.0, 1.2 Hz) corresponding to the phenyl group
connected to the nitro group. Additionally, the nitrophenyl
carbon signals appeared at different magnetic fields at dC
120.0 (2CH), 124.0 (2CH), 140.2 (NO2–C–Ph), and 143.8
(N–Ph–C). Moreover, COSY H H and C H spectra of 5a and
5d yielded some distinctive d values as given in Fig. 1.
The structure of the obtained products (Scheme 1) excluded
formal [2 + 3] cycloaddition pathways such as that proposed
by Eicher.7-12 The reaction mechanism can be simply described
as due to nucleophilic attack of the amidine group on the
cyclopropenone 1 to form 3a–e (Scheme 1). Subsequently,
further nucleophilic addition of the strained cyclopropenone
on the positively nitrogen occurred to afford the unstable
intermediates 4a–e (Scheme 1). In a fast step, intermediates
4a–e quickly lose a molecule of phenyl isothiocyanate
accompanied by extrusion of a hydride ion to form the stable
heterocyclic compounds 5a–e. It is noteworthy that Eicher9
and recently Aly19 have isolated many oxidised products
during the reaction of benzylidene azines with 1. Moreover,
N-Imidoylthioureas 2a–e were prepared according to ref. 16.
Generalꢀprocedure
Into a 250 cm3 two-necked round bottom flask containing a
solution of 2a–e (2 mmol) in absolute ethanol (100 cm3), a solution
of 1 (0.412g. 2 mmol) in absolute ethanol (20 cm3) was added
dropwise with stirring. The mixture was stirred at room temperature
for 1 h, then at reflux for 10–16 h (the reaction was monitored by
TLC analyses). The solvent was evaporated under vacuum and the
formed solid products were purified by dissolving them in dry acetone
(30 cm3) and then subjected to preparative plate chromatography
(silica gel), toluene: ethyl acetate (10:1). Phenyl isothiocyanate was
separatedasthefastestmigratingzoneandwasanalysedbyTLCanalysis.
The obtained products 5a–e were recrystallised from the stated
solvents.
3-(4-Methoxyphenyl)-2,5,6-triphenylpyrimidin-4(3H)-one
(5a):
Compound 5a was obtained as yellow crystals (0.37 g, 80%),
m.p. 220°C (ethanol). 1H NMR (DMSO-d6): d = 7.88 (dd, 2 H,
J = 8.00, 1.2 Hz,Ar–H), 7.40–7.20 (m, 9 H, Ph–H), 7.00–6.82 (m, 6 H,
Ph–H), 6.75 (dd, 2 H, J = 8.0, 1.2 Hz, Ar–H), 3.95 (s, 3 H, OCH3).
13C NMR: d = 168.8 (C-4), 162.1 (C-2), 150.9 (OCH3–Ph–C), 145.9
(C-6), 132.0 (CH3O–Ph–N–C), 131.4, 130.6, 130.2 (Ph–C), 128.5,
128.2, 127.8, 127.6 (ortho-2Ph–CH), 127.4, 127.2, 127.0, (meta-
2Ph–CH), 126.6, 126.4, 126.0 (para-Ph–CH), 125.0 (meta-2Ph–CH),
δH= 8.10 (δC =124.0)
C = 143.8
δC=
δH= 3.95 (δC = 51.0)
δH= 6.75 (δC=120.0)
132.4
δ
δ
H = 7.88 (δC= 128.5)
CH3
O
δC =169.4
δC= 132.0
δ =168.8
δC
=
O2N
131.4
O
O
N
δ = 140.2
δC =123.2
4
N
δ
H = 7.80 (δC =120.0)
δC = 150.9
δC=124.0
C = 145.9
1
N
N
δ = 130.2
δC = 144.2
δ
C = 130.8
δ
C = 130.6
C = 162.1
5a
δ
δ
C = 161.0
δC
=
δ
132.0
5d
Fig. 1 Distinctive d values of compounds 5a and 5d.
PAPER: 07/4676

JOURNAL OF CHEMICAL RESEARCH 2007 441
References
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6
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Compound 5d was obtained as pale orange crystals (0.21 g, 60%),
1
m.p. 250°C (methanol). H NMR: d = 8.10 (dd, 2 H, J = 8.0,
1.2 Hz, NO2Ph), 7.80 (dd, 2 H, J = 8.0, 1.2 Hz, NO2Ph), 7.60–7.20
(m, 8 H, Ph–H), 7.00–6.80 (m, 7 H, Ph–H). 13C NMR: d = 169.4
(C-4), 161.0 (C-2), 144.2 (C-6), 143.8 (N–C–PhNO2), 140.2
(NO2–Ph–C), 132.4, 132.0, 130.8 (Ph–C), 129.6, 129.4, 129.0
(ortho-2Ph–CH), 128.6, 128.4, 128.0 (meta-2Ph–CH), 127.4, 127.0,
126.0 (para-Ph–CH), 124.0 (NO2–2PhCH), 123.2 (C-5), 120.0
(NO2–2PhCH). IR (KBr): 3070–2990 (w, Ar–CH), 1700 (CO), 1610
(s, C=N), 1496 (s, C=C), 920 (s) cm-1. lmax (CH3CN, lg e, nm): 340
(3.3). MS (m/z,%): 445 [M+] (100), 368 (32), 322 (30), 290 (24),
262 (16), 246 (30), 240 (34), 192 (30), 169 (24), 122 (28), 77 (40).
C28H19N3O3 (445.48) Calcd; C, 75.49; H, 4.30; N, 9.43. Found; C,
75.30; H, 4.22; N, 9.40.
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obtained as yellow crystals (0.25 g, 74%), m.p. 296°C [lit.22,25 295–
296°C].
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Prof Dr Ashraf A. Aly thanks the DAAD foundation for
financial support to stay in Germany, Braunschweig, Institute
for Organic Chemistry.
Receivedꢀ31ꢀMayꢀ2007;ꢀacceptedꢀ16ꢀJulyꢀ2007ꢀ
Paperꢀ07/4676ꢀ doi:ꢀ10.3184/030823407X234563
PAPER: 07/4676