One pot synthesis of spiro pyrimidinethiones/spiro pyrimidinones, quinazolinethiones/quinazolinones, and pyrimidopyrimidines

Article abstract of DOI:10.1002/jhet.282

(Chemical Equation Presented) Condensation of cyclohexane-1,3-dione/ barbituric acid, thiourea/urea, and aromatic aldehyde in the mole ratio of 1:1:3 in solventless reaction in presence of NiCl₂/KI afforded 1,5-diaryl-3-thioxo-2,4-diazaspiro[5.5]undecane-7,11-dione/1,5-diaryl-2, 4-diazaspiro[5.5]undecane-3,7,11-trione analogues and 7,11-diaryl-9-thioxo-2,4, 8,10-tetraazaspiro[5.5]undecane-1,3,5,-trione/7,11-diaryl-2,4,8, 10-tetraazaspiro[5.5] undecane-1,3,5,9-tetraone analogues, respectively. The similar condensation of cyclohexane-1,3-dione/cyclohexanone, thiourea/urea, and aromatic aldehyde/heteroaromatic aldehyde in the mole ratio of 1:1:1 in refluxing methanol afforded 4-aryl/heteroaryl-2-thioxo-1,2,3,4,5,6,7,8- octahydroquinazolin-5-one, 4-aryl/heteroaryl-1,2,3,4,5,6,7,8- octahydroquinazoline-2,5-dione analogues and 4-aryl/heteroaryl-1,2,3,4,5, 6,7,8-octahydroquinazoline-2-thione, 4-aryl/heteroaryl-1,2,3,4,5,6,7,8- octahydroquinazolin-2-one analogues, respectively. Condensation of heterocyclic active methylene compound, barbituric acid, thiourea/urea, and aromatic aldehydes under similar set of conditions in 1:1:1 mole ratio was carried which afforded 5-aryl-7-thioxo-1,2,3,4,5,6,7,8-octahydropyrimido[4,5-d]pyrimidine-2,4- dione/5-aryl-1,2,3,4,5, 6,7,8-octahydropyrimido[4,5-d]pyrimidine-2,4,7-trione analogues. Similar condensation of an active methine compound, 2-acetylcyclohexanone, thiourea/urea, and aromatic aldehydes in the mole ratio of 1:1:1 produced 5-aryl-1-methyl-3-thioxo-2,4-diazaspiro[5.5]undec-1-en-7-one/ 5-aryl-1-methyl-2, 4-diazaspiro[5.5]undec-1-ene-3, 7-dione analogues, the spiro compounds of entirely different kind. All these identifications and characterizations have been based on the elemental analysis and spectral data.

Full text of DOI:10.1002/jhet.282

324
One Pot Synthesis of Spiro Pyrimidinethiones/Spiro
Pyrimidinones, Quinazolinethiones/Quinazolinones, and
Pyrimidopyrimidines
Vol 47
Poonam Gupta, Shallu Gupta, Anand Sachar, Daljeet Kour, Jasbir Singh, and
Rattan L. Sharma*
Department of Chemistry, University of Jammu, Jammu 180006, India
*E-mail: rlsharma_hod@rediffmail.com
Received July 15, 2009
DOI 10.1002/jhet.282
Published online 2 March 2010 in Wiley InterScience (www.interscience.wiley.com).
Condensation of cyclohexane-1,3-dione/barbituric acid, thiourea/urea, and aromatic aldehyde in the
mole ratio of 1:1:3 in solventless reaction in presence of NiCl2/KI afforded 1,5-diaryl-3-thioxo-2,4-
diazaspiro[5.5]undecane-7,11-dione/1,5-diaryl-2,4-diazaspiro[5.5]undecane-3,7,11-trione analogues and
7,11-diaryl-9-thioxo-2,4,8,10-tetraazaspiro[5.5]undecane-1,3,5,-trione/7,11-diaryl-2,4,8,10-tetraazaspiro[5.5]
undecane-1,3,5,9-tetraone analogues, respectively. The similar condensation of cyclohexane-1,3-dione/
cyclohexanone, thiourea/urea, and aromatic aldehyde/heteroaromatic aldehyde in the mole ratio of 1:1:1
in refluxing methanol afforded 4-aryl/heteroaryl-2-thioxo-1,2,3,4,5,6,7,8-octahydroquinazolin-5-one, 4-
aryl/heteroaryl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione analogues and 4-aryl/heteroaryl-1,2,3,4,5,
6,7,8-octahydroquinazoline-2-thione,
4-aryl/heteroaryl-1,2,3,4,5,6,7,8-octahydroquinazolin-2-one
ana-
logues, respectively. Condensation of heterocyclic active methylene compound, barbituric acid, thiourea/
urea, and aromatic aldehydes under similar set of conditions in 1:1:1 mole ratio was carried which
afforded
5-aryl-7-thioxo-1,2,3,4,5,6,7,8-octahydropyrimido[4,5-d]pyrimidine-2,4-dione/5-aryl-1,2,3,4,5,
6,7,8-octahydropyrimido[4,5-d]pyrimidine-2,4,7-trione analogues. Similar condensation of an active
methine compound, 2-acetylcyclohexanone, thiourea/urea, and aromatic aldehydes in the mole ratio of
1:1:1 produced 5-aryl-1-methyl-3-thioxo-2,4-diazaspiro[5.5]undec-1-en-7-one/5-aryl-1-methyl-2, 4-diazas-
piro[5.5]undec-1-ene-3, 7-dione analogues, the spiro compounds of entirely different kind. All these iden-
tifications and characterizations have been based on the elemental analysis and spectral data.
J. Heterocyclic Chem., 47, 324 (2010).
INTRODUCTION
rial [7], antiviral [8], antifungal [9], antiasthematic, anti-
allergic [10], and antitubercular [11a]. In addition to its
diverse biological activity, the quinazoline nucleus is
also a key component in a relatively varied range of col-
ored products [11b]. Compounds possessing pyrimido-
pyrimidine nucleus show potent biological activities
including inhibition of angiogenesis, tumor inhibition
[12], and tyrosine kinase inhibitors [13]. Some of the
pyrimidopyrimidine derivatives, particularly 3-(2-methyl-
phenyl)-10-phenyl-2-thioxothiazolo[4,5-d]pyrimido[2,1-
The synthesis of spiro compounds has been a subject
of great interest to research workers. Spiro derivatives
based on heteropolycyclics have antibacterial, anticon-
vulsant, antitumor, and anticancer activities. Similarly,
condensed heterocyclics containing quinazoline moiety
are ranked among the most versatile biologically active
compounds possessing pharmacological properties like
being anticonvulsant [1, 2], anticoagulant [3], antifibril-
latory [4], cardiac stimulant [5], diuretic [6], antibacte-
C
V
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One Pot Synthesis of Spiro Pyrimidinethiones/Spiro Pyrimidinones,
Quinazolinethiones/Quinazolinones, and Pyrimidopyrimidines
325
Scheme 1
b]pyrimidine [14] have been screened for antifungal
activity against Aspergillus niger and Penicillium
citrinum. These promising biological activities encour-
aged us to prepare some new heterocyclic derivatives.
In the past decade, dihydropyrimidinones and their
derivatives have attracted considerable interest because
they exhibit promising activities as calcium channel
blockers, antihypertensive agents, a-1a-antagonists [15],
and neuropeptide Y (NPY) antagonists. Moreover, sev-
eral alkaloids containing the dihydropyrimidine core
unit have been isolated from marine sources, which also
exhibit interesting biological properties [16], most nota-
bly among these are the batzellandine alkaloids, which
were found to be potent HIV group-120-CD4 inhibitors
[17]. The synthesis of the core heterocyclic nucleus of
dihydropyrimidinones, tetrahydropyrimidinones, partially
reduced quinazolines, and their thio analogues is of
much current importance. The most simple and straight-
forward procedure, first reported by Biginelli in 1893,
involves three-component, one pot condensation of a
ethyl acetoacetate with an aldehyde and urea under
strongly acidic conditions [18]. This procedure is known
as the Biginelli reaction. The major drawback associated
with this protocol is the low yield, particularly for sub-
stituted aromatic and aliphatic aldehydes [19]. Recently,
many synthetic methods for preparing dihydropyrimidi-
nones have been reported including classical conditions,
with microwave and ultrasound irradiation and by using
Lewis acids as well as protic acid promoters such as;
H2SO4 [20], BF3 Et2O/CuCl [21], InCl3 [22], BiCl3
[23], LiClO4 [24], Ag3PW12O40 [25], and FeCl3 6H2O/
HCl [26]. Acidic ionic liquids as effective catalysts for
this transformation were also utilized [27]. However,
some of the reported methods also suffer from
drawbacks such as nonrecyclability, harsh reaction
conditions, long reaction times, the need of an additive,
tedious work-up, and environmental pollution. More-
over, some of the methods are only practical for aro-
matic aldehydes especially the unsubstituted ones.
Therefore, a need still exists for versatile, simple and
environment-friendly processes wehereby DHPMs as
single ring compounds, as a component in condensed
heterocycles and as moieties in spiro heterocyclic sys-
tems can be formed under milder and practical condi-
tions. In recent years, multicomponent coupling reac-
tions [28] for the synthesis of the title and closely
related compounds have received considerable attention.
It is a major attraction to chemists because two or more
steps in the synthetic sequence can be carried out with-
out the isolation of intermediates. Thus, the synthesis of
compounds containing heterocyclic nucleus is of current
interest under this strategy. We, herein, report three
component coupling reaction (Biginelli type of reaction),
which provides an easy access to spiro and condensed/
fused heterocycles in fairly good yield. It is worthwhile
to mention here, that we proposed a new one pot
method for synthesizing novel spiro pyrimidinethiones/
spiro pyrimidinones; varied substituted and reduced qui-
nazolinethiones/quinazolinones and condensed pyrimido-
pyrimidines. In this work, we describe a general and
practical route for the Biginelli type cyclocondensation
reactions using NiCl2 þ KI as the catalyst. This can
serve as a general method which provides an easy
access to spiro and condensed systems in excellent
yield.
RESULTS AND DISCUSSION
A facile and one pot combination that not only pre-
serves the simplicity of Biginelli’s one pot reaction but
also consistently produces excellent yields of the spiro
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Vol 47
Scheme 2
pyrimidinethiones/spiro pyrimidinones (1a-f/10a-f) has
been developed as shown in Scheme 1. In a typical gen-
eral experimental procedure by using highly exceptional
conditions, a melt of the mixture of 1,3-dicarbonyl com-
pound (cyclohexane-1,3-dione or barbituric acid), thiou-
rea/urea, an aromatic aldehyde in the mole ratio of 1:1:3
was stirred without using any solvent at 70–80ꢀC in the
presence of catalytic amount of NiCl2 þ KI for a certain
period of time required to complete the reaction (TLC),
resulting in the formation of spiro pyrimidinethiones/
spiro pyrimidinones. To study the generality of this pro-
cess, many transformations illustrating this novel and
general method for the synthesis of spiro pyrimidine-
thiones/spiro pyrimidinones were studied and the physi-
cal data including elemental analysis of the products is
summarized in experimental section. A variety of substi-
tuted aromatic aldehydes and the cyclic dicarbonyl com-
pounds afforded high yields of products in high purity.
These reactions leading to the formation of spiro pyrimi-
dinethiones/spiro pyrimidinones were confounded from
the green perspectives, by the requirements for extrac-
tive isolation followed by recrystallization to afford ma-
terial of a suitable quality. The solvent free approach
afforded good yields of products examined during the
course of this study. In majority of instances, solvent
free approach generated pyrimidinethiones/pyrimidi-
nones of exceptionally good purity. For comparison,
condensation of an active methine compound, 2-acetyl-
cyclohexanone (a cyclic b -diketone), thiourea/urea, and
aromatic aldehyde in the mole ratio of 1:1:1 produced
altogether an unexpected and a novel spiro compound
instead of a normal condensed product (a quinazoline
analogue), which was characterized as 5-aryl-1-methyl-
3-thioxo-2,4-diazaspiro[5.5]undec-1-en-7-one/5-aryl-1-methyl-
2,4-diazaspiro[5.5]undec-1-ene-3,7-dione analogue (2a-
e/20a-e) as shown in Scheme 2. In another general ex-
perimental procedure, condensation of cyclohexane-1,3-
dione, thiourea/urea, and aromatic aldehyde/heteroaro-
matic aldehyde in the mole ratio of 1:1:1 in refluxing
methanol for 10–12 h resulted in the formation of 4-
aryl/heteroaryl-2-thioxo-1,2,3,4,5,6,7,8-octahydroquinazolin-
5-one/4-aryl/heteroaryl-1, 2,3,4,5,6,7,8-octahydro quin-
azoline-2,5-dione derivatives (3a-e/30a-e) as shown in
Scheme 3. Similarly, condensation of cyclohexanone,
thiourea/urea, and aromatic or heteroaromatic aldehydes
produces 4-aryl/heteroaryl-1,2,3,4,5,6,7,8-octahydroqui-
nazoline-2-thione/4-aryl/heteroaryl-1,2,3,4,5,6,7,8 octa-
hydroquinazolin-2-one analogues (4a-e/40a-e) as shown
in Scheme 4. Condensation of active methylene hetero-
cyclic compound, barbituric acid, thiourea/urea, and aro-
matic aldehyde under similar set of conditions afforded
5-aryl-7-thioxo-1,2,3,4,5,6,7,8-pyrimidine-2,4,7-trione deriv-
atives (5a-d/50a-d) as shown in Scheme 5. The physical
data of the products of all these reactions has been
included in the experimental section. In conclusion,
three-component condensation provides an efficient and
improved method for the synthesis of spiro and con-
densed heterocycles. Moreover, this method offers
Scheme 3
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DOI 10.1002/jhet

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One Pot Synthesis of Spiro Pyrimidinethiones/Spiro Pyrimidinones,
Quinazolinethiones/Quinazolinones, and Pyrimidopyrimidines
327
Scheme 4
1
several advantages including high yield, simple work-up
procedure and is free from pollution. The structures of
all these compounds were established by elemental anal-
5.18 due to one proton, H-5 in H NMR spectrum of 2c
confirmed the generation of a substituted and functional-
ized cyclohexanespiropyrimidine system, characterized
for this compound. The only characteristic difference in
1
ysis and spectral studies (IR, H NMR, and 13C NMR
1
spectra of some compounds).
the H NMR spectra of quinazoline compounds 3 and 4
A characteristic multiplet at d 2.0–2.35 due to six
protons of the trimethylene chain of the cyclohexane
component of the spiro system; a sharp singlet signal
due to two similar benzylic methyl protons corresponding
to six protons at d 2.40 and a downfield singlet around d 5.0
due to two identical protons at positions 1 and 5 of the spiro
system along with the usual appearance of aromatic protons
is that in former we have a slightly downfield multiplet
due to six protons of the trimethylene chain and in the
latter a slightly up field multiplet due to eight protons of
the tetramethylene chain. In compounds 5, where in the
1H NMR spectra there is a dearth of protons on the car-
bon atoms of the heterocyclic system, the only promi-
nent singlet characterizing the system is due to a single
proton at d 4.70, supplemented by the elemental analysis
data and characteristic IR peaks data as detailed in the
experimental part of individual compounds.
In products 1a-f and 10a-f, besides the stereochemistry
involved due to spiro system of the 2 six-membered het-
erocyclic and carbocyclic ring, there are two similar chi-
ral centers on one of the rings of the spiro system. So,
1
in the H NMR spectrum speaks unequivocally of the char-
acterized 1,5-bis(p-methylphenyl)-3-thioxo-2,4-diazas-
piro[5.5]undecane-7,11-dione structure of the thioxo
compound 1a. The prominent absence of appearance of
methylene chain protons, presence of two closely
located sharp singlet signals of three protons of each of
the two methoxyl groups, one at d 3.68 and the other at
d 3.72 and more downfield appearance of a signal of
two protons due to H-7 and H-11 of the spiro system at
Scheme 5
1
d 5.25 in the H NMR spectra of 1f not only confirmed
but distinguished this tetrazaspiro system from the dia-
zaspiro system. Disappearance of a triplet signal due to
methine proton of 2-acetylcyclohexanone and appear-
ance of a slightly upfield singlet at d 1.22 due to methyl
group as compared with that of 2-acetylcyclohexanone
(d 2.68); a multiplet due to eight protons of tetramethy-
lene chain at d 1.79–2.25; a signal at d 3.70 due to
methoxyl protons and a highly downfield singlet at d
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P. Gupta, S. Gupta, A. Sachar, D. Kour, J. Singh, and R. L. Sharma
Vol 47
Table 1
Antimicrobial activity of 1,5-diaryl-3-thioxo-2,4-diazaspiro[5.5]undecane-7,11-dione/1,5-diaryl-2,4-diazaspiro[5.5]undecane-3,7,11-trione (1a-c/10a-c) and
7,11-diaryl-9-thioxo-2,4,8,10-tetrazaspiro[5.5]undecane-1,3,5-trione/7,11-diaryl-2,4,8,10-tetrazaspiro[5.5]undecane-1,3,5,9 tetraone (1d-e/10d-e).
Antibacterial activity
Antifungal activity
Compd No.
Escherichia coli
Bacillus subtilis
Bacillus cereus
Aspergillus niger
Penicillium species
Cladosporium species
1a
1b
1c
1d
1e
10
11
14
15
17
19
12
10
16
17
19
17
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
13
14
16
17
20
20
14
13
17
16
19
18
1f
10a
10b
10c
10d
10e
10f
Standard norfloxacin: Escherichia coli 28, Bacillus subtills 26, Bacillus cereus 28; standard fluconazol: Aspergillus niger 32, Penicillium species
25, Cladosporium species 23.
theoretically three distereoisomers (not four dister-
eoisomers and a pair of racemates) should exist includ-
ing a pair of enantiomers and a meso (optically inactive)
stereomer for all these compounds. In this study, it
could not be established whether entirely the meso ster-
eomer is formed or one of the optically active enantiom-
ers or a mixture of all the stereomers is formed. How-
ever, from the almost zero specific optical rotation
values observed for these compounds, it could be sum-
marized that either the only meso stereoisomer or almost
a 50:50 racemic mixture is formed. The resolution into
enantiomers in this study could not be carried on suc-
cessfully and is under active study presently. The com-
pounds 2a-e, 20a-e, 3a-e, 30a-e, 4a-e, 40a-e, 5a-d, and
50a-d were all obtained also as racemates.
Antimicrobial activity. Some of the compounds
were screened for their antibacterial activity against
Escherichia coli, Bacillus sublitis, and Bacillus cereus
at concentration of 1000 lg and for antifungal activity
against Aspergillus niger, Penicillium species, and Cla-
dosporium species at the same concentration by well
diffusion technique [16,17,29–33]. Standard antibacterial
norfloxacin and antifungal fluconazole were also
screened under similar conditions for a comparison. The
zones of inhibition formed were measured [34] in milli-
meters and are shown in Table 1.
antifungal activity and noneffective against other
species.
EXPERIMENTAL
General. Melting points were measured in open capillaries
on perfit melting point apparatus and are incorrect. IR spectra
on KBr were recorded on Brucker-4800 infrared spectrometer.
NMR and EIMS/HRMS spectra were recorded on Brucker
AC-400 (400 MHz and 100 MHz) and JEOL D-300 mass
spectrometer, respectively. Elemental analysis was carried out
on simple CHNS analyzer (CHNS-932, LECO Corporation,
USA). 1H and 13C chemical shifts are reported in parts per
million (ppm) from tetramethylsilane (TMS) as internal stand-
ard. All experiments were performed in oven dried glass appa-
ratus. SISCO silica was used as adsorbent for TLC (0.5 mm
thick plates) and TLC plates were eluted with 1:9 ratios of
ethyl acetate and n-hexane. The column chromatography was
performed over silica gel (60–120 mesh) with graded solvent
systems of ethyl acetate-pet. ether (60–80).
General procedure for the synthesis of 1,5-diaryl-3-thi-
oxo-2,4-diazaspiro[5.5]undecane-7,11-dione/1,5-diaryl-2,4-
diazaspiro[5.5]undecane-3,7,11-trione (1a-f/10a-f). To
a
magnetically stirred melt of aromatic aldehyde (3 moles) and
cyclic active methylene compound (cyclohexane-1,3-dione or
barbituric acid) (1 mole) at (70–80ꢀC); thiourea/urea (1 mole)
and NiCl2 þ KI (0.1 mole) were added at this temperature.
The mixture was stirred at 110ꢀC for 6–8 h. After the comple-
tion of the reaction as monitored by TLC, the reaction mixture
was cooled at room temperature and poured onto crushed ice
and again stirred for 10–20 min. The solid thus separated was
filtered, washed with cold water and crystallized from ethanol
to get 1a-f/10a-f.
Antimicrobial activity of 1,5-diaryl-3-thioxo-2,4-dia-
zaspiro[5.5]undecane-7,11-dione/1,5-diaryl-2,4-diazaspir-
o[5.5]undecane-3,7,11-trione (1a-c/10a-c) and 7,11-dia-
ryl-9-thioxo-2,4,8,10-tetrazaspiro[5.5]undecane-1,3, 5-tri-
one/7,11-diaryl-2,4,8,10-tetrazaspiro[5.5]undecane-1,3,5,9
tetraone (1d-e/10d-e).
It was interesting to observe summarily that all the
compounds 1a-f and 10a-f were highly effective against
E. coli for antibacterial and Cladosporium species for
1,5-Bis-(p-methylphenyl)-3-thioxo-2,4-diazaspiro[5.5] undecane-
7,11-dione (1a). Yield 78%; Mp 210–212ꢀC; IR (KBR, v,
1
cmꢁ1): 1185 (C¼¼S), 1650–1710 (C¼¼O), 3360–3430 (NH); H
NMR (CDCl3) d: 2.00–2.35 (m, 6H, 3 ꢂ CH2), 2.40 (s, 3H,
CH3), 2.43 (s, 3H, CH3, 4.99 (s, 2H, 1,5–Hs), 7.00–7.05 (m,
8H, ArHs), and 7.90–8.20 (bs, 2H, NH, D2O exchangable).
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One Pot Synthesis of Spiro Pyrimidinethiones/Spiro Pyrimidinones,
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329
Anal. Calcd. for C23H24N2O2S: C, 70.40; H, 6.12; N, 7.14; S,
8.16. Found: C, 70.23; H, 6.14; N, 7.16; S, 8.19.
ArHs), and 7.85–8.20 (bs, 2H, NH); 13C NMR d: 15.5, 40.5,
44.8, 59.7, 92.4, 119.7, 139.3, 142.0, 165.2, 167.6, 218.9.
Anal. Calcd. for C23H24N2O5: C, 67.64; H, 5.88; N, 6.86.
Found: C, 67.46; H, 5.90; N, 6.74.
1,5-Bis-(3,4-dimethoxyphenyl)-2,4-diazaspiro[5.5]undecane-
3,7,11-trione (10c). Yield 87%; Mp 232–234ꢀC; IR (KBR, v,
cmꢁ1): 1670–1705 (C¼¼O), 3390–3440 (NH); 1H NMR
(CDCl3) d: 2.00–2.10 (m, 6H, 3 ꢂ CH2), 3.60 (s, 3H, OCH3),
3.64 (s, 3H, OCH3), 3.70 (s, 3H, OCH3), 3.74 (s, 3H, OCH3),
4.83 (s, 2H, 1,5-H), 6.82–7.10 (m, 6H, ArHs), and 7.80–8.15
(bs, 2H, NH); 13C NMR d: 16.2, 38.5, 49.1, 56.3, 90.3, 115.2,
122.5, 131.4, 147.8, 154.3, 211.2. Anal. Calcd. for
C25H28N2O7: C, 64.10; H, 5.98; N, 5.98. Found: C, 63.92; H,
5.96; N, 5.91.
1,5-Bis-(4-methoxyphenyl)-3-thioxo-2,4-diazaspiro[5.5]un-
decane-7,11-dione (1b). Yield 75%; Mp 204–206ꢀC; IR
(KBR, v, cmꢁ1): 1180 (C¼¼S), 1620–1700 (C¼¼O), 3350–3420
1
(NH); H NMR (CDCl3) d: 1.90–2.30 (m, 6H, 3 ꢂ CH2), 3.70
(s, 3H, OCH3), 3.72 (s, 3H, OCH3), 4.90 (s, 2H, 1,5–Hs),
6.75–7.05 (m, 8H, ArHs), and 7.88–8.00 (bs, 2H, NH); 13C
NMR d: 16.2, 38.5, 47.8, 56.1, 90.5, 114.0, 129.1, 131.0,
159.2, 163.1, 211.1. Anal. Calcd. for C23H24N2O4S: C, 65.09;
H, 5.66; N, 6.60; S, 7.54. Found: C, 64.91; H, 5.68; N, 6.53;
S, 7.59.
1,5-Bis-(3,4-dimethoxyphenyl)-3-thioxo-2,4-diazaspiro[5.5]
undecane-7,11-dione (1c). Yield 75%; Mp 230–232ꢀC; IR
(KBR, v, cmꢁ1): 1178 (C¼¼S), 1670–1705 (C¼¼O), 3290–3430
7,11-Bis-(p-methylphenyl)-2,4,8,10-tetrazaspiro[5.5]un-
decane-1,3,5,9-tetraone (10d). Yield 80%; Mp 246–248ꢀC;
1
(NH); H NMR(CDCl3) d: 1.95–2.35 (m, 6H, 3 ꢂ CH2), 3.65
1
(s, 3H, OCH3), 3.70 (s, 3H, OCH3), 3.73 (s, 3H, OCH3), 3.75
(s, 3H,OCH3), 4.87 (s, 2H, 1,5-H), 6.60–6.90 (m, 6H, ArHs)
and 7.82–8.01 (bs, 2H, NH); 13C NMR d: 16.4, 38.3, 48.9,
56.1, 90.0, 114.8, 123.5, 130.8, 152.5, 170.1, 211.4. Anal.
Calcd. for C25H28N2O6S: C, 61.98; H, 5.78; N, 5.78; S, 6.61.
Found: C, 61.80; H, 5.80; N, 5.82; S, 6.55.
IR (KBR, v, cmꢁ1): 1672–1710 (C¼¼O), 3380–3460 (NH); H
NMR (CDCl3) d: 2.20 (s, 3H, CH3), 2.25 (s, 3H, CH3), 5.15
(s, 2H, 7, 11–Hs), 7.00–7.10 (m, 8H, ArHs), and 7.80–8.15
(bs, 4H, NH). Anal. Calcd. for C21H20N4O4: C, 64.28; H, 5.10;
N, 14.28. Found: C, 64.10; H, 5.12; N, 14.25.
7,11-Bis-(4-methoxyphenyl)-2,4,8,10-tetrazaspiro[5.5]undecane-
1,3,5,9-tetraone (10e). Yield 90%; Mp 240–242ꢀC; IR (KBR, v,
cmꢁ1): 1680–1720 (C¼¼O), 3270–3420 (NH); 1H NMR
(CDCl3) d: 3.70 (s, 3H, OCH3), 3.75 (s, 3H, OCH3), 5.20 (s,
2H, 7, 11–Hs), 6.80–7.20 (m, 8H, ArHs), and 7.82–8.20 (bs,
4H, NH). Anal. Calcd. for C21H20N4O6: C, 59.43; H, 4.71; N,
13.20. Found: C, 59.25; H, 4.72; N, 13.14.
7,11-Bis-(p-methylphenyl)-9-thioxo-2,4,8,10-tetrazaspiro[5.5]
undecane-1,3,5-trione (1d). Yield 77%; Mp 240–242ꢀC; IR
(KBR, v, cmꢁ1): 1175 (C¼¼S), 1670–1705 (C¼¼O), 3290–3430
(NH); 1H NMR (CDCl3) d: 2.25 (s, 3H, CH3), 2.30 (s, 3H,
CH3), 5.29 (s, 2H, 7, 11–Hs), 7.10–7.20 (m, 8H, ArHs), and
7.89–8.20 (bs, 4H, NH). Anal. Calcd. for C21H20N4O3S: C,
61.76; H, 4.90; N, 13.72; S, 7.84. Found: C, 61.58; H, 4.91;
N, 13.75; S, 7.73.
7,11-Bis-(4-methoxyphenyl)-9-thioxo-2,4,8,10-tetrazaspiro[5.5]
undecane-1,3,5-trione (1e). Yield 82%; Mp 234–236ꢀC; IR
(KBR, v, cmꢁ1): 1182 (C¼¼S), 1660–1700 (C¼¼O), 3280–3425
(NH); 1H NMR (CDCl3) d: 3.72 (s, 3H, OCH3), 3.74 (s, 3H,
OCH3), 5.27 (s, 2H, 7, 11–Hs), 6.90–7.10 (m, 8H, ArHs), and
7.87–8.22 (bs, 4H, NH); 13C NMR d: 52.2, 56.8, 72.5, 114.3,
122.8, 132.4, 140.5, 146.0, 150.2, 151.7, 163.0, 176.8. Anal.
Calcd. for C21H20N4O5S: C, 57.27; H, 4.54; N, 12.72; S, 7.27.
Found: C, 57.09; H, 4.55; N, 12.75; S, 7.23.
7,11-Bis-(3,4-dimethoxyphenyl)-9-thioxo-2,4,8,10-tetra-
zaspiro[5.5]undecane-1,3,5-trione (1f). Yield 86%; Mp 244–
246ꢀC; IR (KBR, v, cmꢁ1): 1180 (C¼¼S), 1665–1700 (C¼¼O),
3270–3420 (NH); 1H NMR (CDCl3) d: 3.68 (s, 3H, OCH3),
3.70 (s, 3H, OCH3), 3.72 (s, 3H, OCH3), 3.75 (s, 3H, OCH3),
5.25 (s, 2H, 7,11-H), 6.67–6.90 (m, 6H, ArHs), and 7.89–8.90
(bs,4H,NH); 13C NMR d: 52.4, 56.2, 71.4, 114.7, 115.0, 121.8,
132.2, 139.2, 144.7, 147.5, 163.1, 176.1. Anal. Calcd. for
C23H24N4O7S: C, 55.20; H, 4.8; N, 11.2; S, 6.4. Found: C,
55.01; H, 5.0; N, 11.5; S, 6.9.
7,11-Bis-(3,4-dimethoxyphenyl)-2,4,8,10-tetrazaspiro[5.5]
undecane-1,3,5,9-tetraone (10f). Yield 87%; Mp 250–252ꢀC;
1
IR (KBR, v, cmꢁ1): 1675–1710 (C¼¼O), 3280–3450 (NH); H
NMR (CDCl3) d: 3.65 (s, 3H, OCH3), 3.68 (s, 3H, OCH3),
3.70 (s, 3H, OCH3), 3.74 (s, 3H, OCH3), 5.15 (s, 2H, 7,11-
H), 6.87–7.10 (m, 6H, ArHs), and 7.60–8.40 (bs, 4H, NH);
13C NMR d: 55.6, 59.8, 86.4, 118.2, 120.0, 128.8, 138.9,
140.7, 148.8, 150.8, 163.9, 180.1. Anal. Calcd. for
C23H24N4O8: C, 57.02; H, 4.95; N, 11.57. Found: C, 56.84;
H, 4.97; N, 11.61.
General procedure for the synthesis of 5-aryl-1-methyl-3-
thioxo-2,4-diazaspiro[5.5]undec-1-en-7-one/5-aryl-1-methyl-
2,4-diazaspiro[5.5]undec-1-ene-3,7-dione (2a-e/20a-e). These
heterocycles were prepared by following the same procedure
as mentioned for (1a-f/10a-f) by condensing appropriate aro-
matic aldehyde, thiourea/urea, and 2-acetylcyclohexanone in
the mole ratio of 1:1:1 simply by stirring at 100–110ꢀC for 6
h without using any solvent and catalyst. The work of the
reaction was done as usual by pouring ice cold water on to the
reaction mixture residue. The spectral characterizations of the
synthesized compounds are as follows:
1,5-Bis-(p-methylphenyl)-2,4-diazaspiro[5.5]undecane-3,7,11-
trione (10a). Yield 90%; Mp 212–214ꢀC; IR (KBR, v, cmꢁ1):
1660–1700 (C¼¼O), 3382–3470 (NH). 1H NMR (CDCl3) d:
2.10–2.25 (m, 6H, 3 ꢂ CH2), 2.43 (s, 3H, CH3), 2.45 (s, 3H,
CH3), 4.87–5.01 (s, 2H, 1,5–Hs), 6.95–7.10 (m, 8H, ArHs),
and 7.80–8.15 (bs, 2H, NH). Anal. Calcd. for C23H24N2O3: C,
73.40; H, 6.38; N, 7.44. Found: C, 73.21; H, 6.40; N, 7.38.
1,5-Bis-(4-methoxyphenyl)-2,4-diazaspiro[5.5]undecane-
3,7,11-trione (10b). Yield 80%; Mp 210–211ꢀC; IR (KBR, v,
cmꢁ1): 1675–1710 (C¼¼O), 3370–3430 (NH); 1H NMR
(CDCl3) d: 2.15–2.30 (m, 6H, 3 ꢂ CH2), 3.55 (s, 3H, OCH3),
3.88 (s, 3H, OCH3), 4.97 (s, 2H, 1,5–Hs), 6.90–7.15 (m, 8H,
1-Methyl-5-phenyl-3-thioxo-2,4-diazaspiro[5.5]undec-1-en-
7-one (2a). Yield 77%; Mp 170–172ꢀC; IR (KBR, v, cmꢁ1):
1180 (C¼¼S), 1680–1700 (C¼¼O), 3420 (NH); 1H NMR
(CDCl3) d: 1.32 (s, 3H, CH3), 1.95–2.30 (m, 8H, 4 ꢂ CH2),
5.26 (s, 1H, 5-H), 7.01–7.03 (m, 5H, ArHs), and 9.01 (bs, 1H,
NH). Anal. Calcd. for C16H18N2OS: C, 67.13; H, 6.29; N,
9.79; S, 11.18. Found: C, 66.92; H, 6.30; N, 9.84; S, 11.23.
1-Methyl-5-(p-methylphenyl)-3-thioxo-2,4-diazaspiro[5.5]
undec-1-en-7-one (2b). Yield 74%; Mp 178–180ꢀC; IR
(KBR, v, cmꢁ1): 1175 (C¼¼S), 1670–1690 (C¼¼O), 3410 (NH);
1H NMR (CDCl3) d: 1.30 (s, 3H, CH3), 1.90–2.30 (m, 8H, 4
ꢂ CH2), 5.20 (s, 1H, H-5), 7.01–7.01 (m, 4H, ArHs), and 9.01
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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P. Gupta, S. Gupta, A. Sachar, D. Kour, J. Singh, and R. L. Sharma
Vol 47
(bs, 1H, NH);13C NMR d: 12.2, 20.6, 22.1, 27.4, 36.9, 38.2,
45.1, 62.0, 128.0, 129.2, 134.7, 136.2, 164.4, 175.0, 211.2.
Anal. Calcd. for C17H20N2OS: C, 68.0; H, 6.66; N, 9.33; S,
10.66. Found: C, 67.79; H, 6.68; N, 9.35; S, 10.69.
5-(4-Methoxyphenyl)-1-methyl-3-thioxo-2,4-diazaspiro[5.5]
undec-1-en-7-one (2c). Yield 70%; Mp 184–186ꢀC; IR (KBR,
v, cmꢁ1): 1182 (C¼¼S), 1665–1695 (C¼¼O), 3415 (NH); 1H
NMR (CDCl3) d: 1.22 (s, 3H, CH3), 1.79–2.25 (m, 8H, 4 ꢂ
CH2), 3.70 (s, 3H, OCH3), 5.18 (s, 1H, H-5), 6.98–7.01 (m,
4H, ArHs), and 8.90 (bs, 1H, NH). Anal. Calcd. for
C17H20N2O2S: C, 64.55; H, 6.32; N, 8.86; S, 10.12. Found: C,
64.36; H, 6.34; N, 8.89; S, 10.15.
5-(3,4-Dimethoxyphenyl)-1-methyl-3-thioxo-2,4-diazaspiro[5.5]
undec-1-en-7-one (2d). Yield 72%; Mp 192–193ꢀC; IR (KBR,
v, cmꢁ1): 1178 (C¼¼S), 1680–1700 (C¼¼O), 3400 (NH); 1H
NMR (CDCl3) d: 1.15 (s, 3H, CH3), 1.74–2.29 (m, 8H, 4 ꢂ
CH2), 3.62 (s, 3H, OCH3), 3.70 (s, 3H, OCH3), 5.15 (s, 1H,
H-5), 6.98–7.00 (m, 3H, ArHs), and 8.75 (bs, 1H, NH). Anal.
Calcd. for C18H22N2O3S: C, 62.42; H, 6.35; N, 8.09; S, 9.24.
Found: C, 62.24; H, 6.37; N, 8.14; S, 9.28.
5-(p-Chlorophenyl)-1-methyl-3-thioxo-2,4-diazaspiro[5.5]
undec-1-en-7-one (2e). Yield 74%; Mp 220–222ꢀC; IR
(KBR, v, cmꢁ1): 1180 (C¼¼S), 1650–1690 (C¼¼O), 3380 (NH);
1H NMR (CDCl3) d: 1.25 (s, 3H, CH3), 1.80–2.20 (m, 8H, 4
ꢂ CH2), 5.29 (s, 1H, H-5), 7.05–7.25 (m, 4H, ArHs), and 9.05
(bs, 1H, NH);13C NMR d: 12.8, 22.2, 27.8, 38.6, 39.2, 45.2,
50.2, 128.7, 131.0, 137.5, 164.4, 173.8, 211.5. Anal. Calcd. for
C16H17N2OSCl: C, 59.90; H, 5.30; N, 8.73; S, 9.98. Found: C,
59.71; H, 5.32; N, 8.79; S, 9.95.
1-Methyl-5-phenyl-2,4-diazaspiro[5.5]undec-1-ene-3,7-dione
(20a). Yield 77%; Mp 172–174ꢀC; IR (KBR, v, cmꢁ1): 1660–
1705 (C¼¼O), 3470 (NH); 1H NMR (CDCl3) d: 1.32 (s, 3H,
CH3), 1.80–2.05 (m, 8H, 4 ꢂ CH2), 5.76 (s, 1H, 5-H), 7.41–
7.83 (m, 5H, ArHs), and 9.11 (bs, 1H, NH). Anal. Calcd. for
C16H18N2O2: C, 71.11; H, 6.66; N, 10.37. Found: C, 71.19; H,
6.62; N, 10.40.
1-Methyl-5-(p-methylphenyl)-2,4-diazaspiro[5.5]undec-1-ene-
3,7-dione (20b). Yield 76%; Mp 180–182ꢀC; IR (KBR, v,
cmꢁ1): 1670–1700 (C¼¼O), 3466 (NH); 1H NMR (CDCl3) d:
1.20 (s, 3H, CH3), 1.95–2.20 (m, 8H, 4 ꢂ CH2), 4.90 (s, 1H,
H-5), 6.90–7.21 (m, 4H, ArHs), and 9.28 (bs, 1H, NH); 13C
NMR d: 15.2, 22.8, 27.8, 30.4, 34.8, 38.9, 46.2, 60.2, 126.0,
128.1, 139.5, 149.8, 169.8, 185.8, 230.2. Anal. Calcd. for
C17H20N2O2: C, 71.83; H, 7.04; N, 9.85. Found: C, 71.64; H,
7.06; N, 9.80.
5-(4-Methoxyphenyl)-1-methyl-2,4-diazaspiro[5.5]undec-1-
ene-3,7-dione (20c). Yield 74%; Mp 189–191ꢀC; IR (KBR, v,
cmꢁ1): 1675–1692 (C¼¼O), 3410 (NH); 1H NMR (CDCl3) d:
1.32 (s, 3H, CH3), 2.10–2.25 (m, 8H, 4 ꢂ CH2), 3.72 (s, 3H,
OCH3), 4.95 (s, 1H, H-5), 6.90–7.00 (m, 4H, ArHs), and 8.72
(bs, 1H, NH). Anal. Calcd. for C17H20N2O3: C, 68.0; H, 6.6;
N, 9.33. Found: C, 67.82; H, 6.8; N, 9.38.
5-(3,4-Dimethoxyphenyl)-1-methyl-2,4-diazaspiro[5.5]undec-
1-ene-3,7-dione (20d). Yield 76%; Mp 191–201ꢀC; IR (KBR,
v, cmꢁ1): 1690–1710 (C¼¼O), 3410 (NH); 1H NMR (CDCl3)
d: 1.15 (s, 3H, CH3), 2.05–2.29 (m, 8H, 4 ꢂ CH2), 3.7 0 (s,
3H, OCH3), 3.74 (s, 3H, OCH3), 5.05 (s, 1H, H-5), 6.88–7.10
(m, 3H, ArHs), and 8.76 (bs, 1H, NH). Anal. Calcd. for
C18H22N2O4: C, 65.45; H, 6.66; N, 8.48. Found: C, 65.27; H,
6.68; N, 8.54.
5-(p-Chlorophenyl)-1-methyl-2,4-diazaspiro[5.5]undec-1-ene-
3,7-dione (20e). Yield 72%; Mp 221–223ꢀC; IR (KBR, v,
cmꢁ1): 1670–1700 (C¼¼O), 3420 (NH); 1H NMR (CDCl3)
d: 1.30 (s, 3H, CH3), 1.70–2.10 (m, 8H, 4 ꢂ CH2), 4.99 (s,
1H, H-5), 7.00–7.25 (m, 4H, ArHs), and 8.90 (bs, 1H, NH);
13C NMR d: 15.7, 25.8, 28.9, 39.9, 40.5, 50.8, 54.8, 130.2,
134.6, 150.3, 168.4, 178.8, 220.4. Anal. Calcd. for
C16H17N2O2Cl: C, 63.05; H, 5.58; N, 9.19. Found: C, 62.87;
H, 5.59; N, 9.24.
General procedure for the synthesis of reduced 4-aryl/
heteroaryl-2-thioxo-quinazolin-5-one,
4-aryl/heteroaryl-
quinazoline-2,5-dione (3a-e/30a-e), 4-aryl/heteroaryl quinaz-
oline-2-thione/4-aryl/heteroaryl-quinazolin-2-one (4a-e/40a-
e), and 5-aryl-7-thioxo pyrimidopyrimidine-2,4-dione/5-
aryl-pyrimidopyrimidine-2,4,7-trione (5a–d/50a-d). A highly
grinded and finally powdered homogeneous trinary mixture of
appropriate aromatic/hetero aromatic aldehyde (1 mole), thiou-
rea/urea (1 mole), and cyclohexane-1,3-dione/cyclohexanone/
barbituric acid (1 mole) in 70–80 mL of methanol was
refluxed for 10–12 h. After the completion of reaction as
monitored by TLC, the reaction mixture was concentrated to
one-third of its volume and was then poured onto ice cold
water. The precipitate separated out, filtered, washed, dried,
and further recrystallized from ethanol to get the required
product.
4-(p-Methylphenyl)-2-thioxo-1,2,3,4,5,6,7,8-octahydroquina-
zolin-5-one (3a). Yield 80%; Mp 225–227ꢀC; IR (KBR, v,
1
cmꢁ1): 1172 (C¼¼S), 1692 (C¼¼O), 3430–3442 (NH); H NMR
(CDCl3) d: 1.60–2.38 (m, 6H, 3 ꢂ CH2), 2.30 (s, 3H, CH3),
4.89 (s, 1H, 4–H), 7.02–7.24 (m, 4H, ArHs), 7.80 (bs, 1H,
NH), and 9.60 (bs, 1H, NH); 13C NMR d: 16.8, 22.4, 26.8,
34.6, 50.2, 115.3, 116.8, 118.2, 118.9, 124.6, 130.4, 135.3,
144.8, 160.6, 197.2. Anal. Calcd. for C15H16N2OS: C, 66.66;
H, 5.88; N, 10.29; S, 11.76. Found: C, 66.48; H, 5.85; N,
10.29; S, 11.73.
4-(4-Methoxyphenyl)-2-thioxo-1,2,3,4,5,6,7,8-octahydro-
quinazolin-5-one (3b). Yield 78%; Mp 249–251ꢀC; IR
(KBR, v, cmꢁ1): 1190 (C¼¼S), 1620 (C¼¼O), 3435–3445 (NH);
1H NMR (CDCl3) d: 1.45–2.30 (m, 6H, 3 ꢂ CH2), 3.73 (s,
3H, OCH3), 4.74 (s, 1H, 4–H), 6.90–7.21 (m, 4H, ArHs), 7.72
(bs, 1H, NH), and 9.56 (bs, 1H, NH). Anal. Calcd. for
C15H16N2O2S: C, 62.50; H, 5.55; N, 9.72; S, 11.11. Found: C,
62.34; H, 5.59; N, 9.69; S, 11.08.
4-(3,4-Dimethoxyphenyl)-2-thioxo-1,2,3,4,5,6,7,8-octahydro-
quinazolin-5-one (3c). Yield 76%; Mp 240–242ꢀC; IR (KBR,
v, cmꢁ1): 1178 (C¼¼S), 1620 (C¼¼O), 3435–3445 (NH); 1H
NMR (CDCl3) d: 1.40–2.20 (m, 6H, 3 ꢂ CH2), 3.70 (s, 3H,
OCH3), 3.75 (s, 3H, OCH3), 4.70 (s, 1H, 4–H), 6.90–7.25 (m,
3H, ArHs), 7.72 (bs, 1H, NH), 9.55 (s, 1H, NH); 13C NMRd:
16.8, 34.6, 40.6, 48.1, 56.1, 113.4, 114.2, 114.7, 120.6, 135.5,
142.2, 145.4, 147.2, 156.6, 197.4. Anal. Calcd. for
C16H18N2O3S: C, 60.37; H, 5.6; N, 8.58; S, 10.06. Found: C,
60.19; H, 5.7; N, 8.55; S, 10.03.
4-(Indol-3-yl)-2-thioxo–1,2,3,4,5,6,7,8-octahydroquinazo-
lin-5-one (3d). Yield 74%; Mp 253–257ꢀC; IR (KBR, v,
1
cmꢁ1): 1180 (C¼¼S), 1680 (C¼¼O), 3390–3445 (NH); H NMR
(CDCl3) d: 1.70–2.46 (m, 6H, 3 ꢂ CH2), 5.65 (s, 1H, 4–H),
7.04–8.29 (m, 5H, ArHs), 8.59 (s, 1H, exch. NH), 9.41 (s, 1H,
NH), and 10.92 (s, 1H, exch. NH); 13C NMR d: 19.8, 34.6,
40.2, 52.6, 111.0, 111.2, 112.3, 119.2, 120.2, 121.3, 122.5,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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One Pot Synthesis of Spiro Pyrimidinethiones/Spiro Pyrimidinones,
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331
131.4, 136.2, 155.8, 178.0, and 198.0. Anal. Calcd. for
C16H15N3OS: C, 64.64; H, 5.0; N, 14.14; S, 10.77. Found: C,
64.46; H, 5.2; N, 14.16; S, 10.74.
4-(4-Methoxyphenyl)-1,2,3,4,5,6,7,8-octahydroquinazoline-
2-thione (4b). Yield 77%; Mp 256–258ꢀC; IR (KBR, v,
cmꢁ1): 1168 (C¼¼S), 3398–3442 (NH); 1H NMR (CDCl3) d:
1.42–2.32 (m, 8H, 4 ꢂ CH2), 3.71 (s, 3H, OCH3), 4.70 (s, 1H,
4–H), 6.92–7.23 (m, 4H, ArHs), 7.70 (bs, 1H, NH), and 9.52
(bs, 1H, NH). Anal. Calcd. for C15H18N2OS: C, 65.69; H,
6.56; N, 10.21; S, 11.67. Found: C, 65.51; H, 6.55; N, 10.23;
S, 11.70.
4-(3,4-Dimethoxyphenyl)-1,2,3,4,5,6,7,8-octahydroquinazo-
line-2-thione (4c). Yield 78%; Mp 256–258ꢀC; IR (KBR, v,
cmꢁ1): 1175 (C¼¼S), 3435–3445 (NH); 1H NMR (CDCl3) d:
1.40–2.20 (m, 8H, 4 ꢂ CH2), 3.70 (s, 3H, OCH3), 3.75 (s, 3H,
OCH3), 4.70 (s, 1H, 4–H), 6.90–7.25 (m, 3H, ArHs), 7.72 (bs,
1H, NH), and 9.55 (bs, 1H, NH). Anal. Calcd. for
C16H20N2O2S: C, 63.15; H, 6.57; N, 9.2; S, 10.52. Found: C,
62.96; H, 6.59; N, 9.0; S, 10.59.
4-(1,3-Diphenyl-1H-pyrazol-4-yl)-2-thioxo-1,2,3,4,5,6,7,8-
octahydroquinazolin-5-one (3e). Yield 72%; Mp 255–257ꢀC;
IR (KBR, v, cmꢁ1): 1182 (C¼¼S), 1680 (C¼¼O), 3435–3440
1
(NH); H NMR (CDCl3) d: 1.85–2.45 (m, 6H, 3 ꢂ CH2), 5.52
(s, 1H, 4–H), 7.01–7.80 (m, 10H, ArHs), 7.84 (s, 1H, 50H),
7.90 (s, 1H, NH), 10.80 (s, 1H, NH); 13C NMR d: 20.0, 35.6,
40.9, 45.2, 111.6, 117.8, 126.0, 128.4, 129.2, 139.8, 155.4,
157.2, 178.4, 197.7. Anal. Calcd. for C23H20N4OS: C, 69.0; H,
5.0; N, 14.0; S, 8.0. Found: C, 68.83; H, 5.2; N, 13.96; S, 8.5.
4-(p-Methylphenyl)-1,2,3,4,5,6,7,8-octahydroquinazoline-2
5-dione (30a). Yield 82%; Mp 222–223ꢀC; IR (KBR, v,
cmꢁ1): 1660 (C¼¼O), 3430–3442 (NH); 1H NMR (CDCl3) d:
1.48–2.20 (m, 6H, 3 ꢂ CH2), 2.35 (s, 3H, CH3), 4.89 (s, 1H,
4–H), 6.98–7.40 (m, 4H, ArHs), 7.70 (bs, 1H, NH), and 9.55
(bs, 1H, NH). Anal. Calcd. for C15H16N2O2: C, 70.31; H, 6.25;
N, 10.93. Found: C, 70.12; H, 6.23; N, 10.91.
4-(Indol-3-yl)-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione
(4d). Yield 72%; Mp 254–256ꢀC; IR (KBR, v, cmꢁ1): 1172
1
(C¼¼S), 3367–3445 (NH); H NMR (CDCl3) d: 1.72–2.41 (m,
4-(4-Methoxyphenyl)-1,2,3,4,5,6,7,8-octahydroquinazoline-
2,5-dione (30b). Yield 74%; Mp 230–232ꢀC; IR (KBR, v,
8H, 4 ꢂ CH2), 5.60 (s, 1H, 4–H), 7.8–8.20 (m, 5H, ArHs),
8.50 (s, 1H, exch. NH), 9.31 (s, 1H, NH), and 10.23 (s, 1H,
exch. NH). Anal. Calcd. for C16H17N3S: C, 67.84; H, 6.0; N,
14.84; S, 11.30. Found: C, 67.66; H, 6.2; N, 14.89; S, 11.35.
4-(1,3-Diphenyl-1H-pyrazol-4-yl)-1,2,3,4,5,6,7,8-octahy-
droquinazoline-2-thione (4e). Yield 76%; Mp 260–262ꢀC;
1
cmꢁ1): 16,700 (C¼¼O), 3432–3440 (NH); H NMR (CDCl3) d:
1.40–2.15 (m, 6H, 3 ꢂ CH2), 3.71 (s, 3H, OCH3), 4.80 (s, 1H,
4–H), 6.92–7.20 (m, 4H, ArHs), 7.70 (bs, 1H, NH), and 9.58
(bs, 1H, NH). Anal. Calcd. for C15H16N2O3: C, 66.17; H, 5.8;
N, 10.29. Found: C, 65.98; H, 5.6; N, 10.26.
1
IR (KBR, v, cmꢁ1): 1185 (C¼¼S), 3440–3445 (NH); H NMR
4-(3,4-Dimethoxyphenyl)-1,2,3,4,5,6,7,8-octahydroquinazo-
line-2,5-dione (30c). Yield 80%; Mp 241–243ꢀC; IR (KBR, v,
cmꢁ1): 1675 (C¼¼O), 3460–3442 (NH); 1H NMR (CDCl3) d:
1.60–2.40 (m, 6H, 3 ꢂ CH2), 3.72 (s, 3H, OCH3), 3.74 (s, 3H,
OCH3), 5.05 (s, 1H, 4–H), 7.05–7.15 (m, 3H, ArHs), 7.70 (bs,
1H, NH), 9.45 (s, 1H, NH); 13C NMR d: 15.2, 38.6, 44.8,
50.1, 58.2, 115.7, 120.7, 122.8, 130.6, 140.5, 148.2, 150.5,
155.2, 158.9, 200.7. Anal. Calcd. for C16H18N2O4: C, 63.57;
H, 5.96; N, 9.27. Found: C, 63.38; H, 5.98; N, 9.24.
(CDCl3) d: 1.92–2.43 (m, 8H, 4 ꢂ CH2), 5.56 (s, 1H, 4–H),
7.02–7.82 (m, 11H, ArHs and 50H),7.92 (s, 1H, exch. NH),
and 10.83 (s, 1H, exch. NH); 13C NMR d: 21.3, 25.8, 32.2,
38.4, 46.3, 112.2, 115.7, 126.3, 128.3, 129.8, 139.3, 152.8,
157.1, 178.3. Anal. Calcd. for C23H22N4S: C, 74.09; H, 5.69;
N, 14.50; S, 8.29. Found: C, 73.92; H, 5.7; N, 14.59; S, 8.24.
4-(p-Methylphenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-2-
one (40a). Yield 78%; Mp 225–227ꢀC; IR (KBR, v, cmꢁ1):
1678 (C¼¼O), 3338–3440 (NH); 1H NMR (CDCl3) d: 1.72–
2.30 (m, 8H, 4 ꢂ CH2), 2.30 (s, 3H, CH3), 4.96 (s, 1H, 4–H),
7.00–7.10 (m, 4H, ArHs), 7.95 (bs, 1H, NH), and 10.2 (bs,
1H, NH). Anal. Calcd. for C15H18N2O: C, 74.38; H, 7.43; N,
11.57. Found: C, 74.18; H, 7.45; N, 10.62.
4-(Indol-3-yl)-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione
(30d). Yield 76%; Mp 256–258ꢀC; IR (KBR, v, cmꢁ1): 1685
1
(C¼¼O), 3370–3440 (NH); H NMR (CDCl3) d: 1.90–2.30 (m,
6H, 3 ꢂ CH2), 5.25 (s, 1H, 4–H), 7.10–7.25 (m, 5H, ArHs),
7.92 (s, 1H, exch. NH), 9.42 (s, 1H, NH), and 10.82 (s, 1H,
exch. NH); 13C NMR d: 18.9, 38.9, 42.5, 55.6, 118.0, 120.2,
126.9, 129.2, 130.5, 132.3, 136.5, 139.4, 140.2, 158.8, 188.0,
200.8. Anal. Calcd. for C16H15N3O2: C, 68.32; H, 5.33; N,
14.94. Found: C, 68.14; H, 5.31; N, 14.90.
4-(4-Methoxyphenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-2-
one (40b). Yield 75%; Mp 251–253ꢀC; IR (KBR, v, cmꢁ1):
1670 (C¼¼O), 3394–3435 (NH); 1H NMR (CDCl3) d: 1.70–
2.31 (m, 8H, 4 ꢂ CH2), 3.73 (s, 3H, OCH3), 4.85 (s, 1H, 4–
H), 7.00–7.23 (m, 4H, ArHs), 7.85 (bs, 1H, NH), and 10.5 (bs,
1H, NH). Anal. Calcd. for C15H18N2O2: C, 69.76; H, 6.97; N,
1 0.85. Found: C, 69.68; H, 6.99; N, 10.92.
4-(1,3-Diphenyl-1H-pyrazol-4-yl)-1,2,3,4,5,6,7,8-octahydro-
quinazoline-2,5-dione (30e). Yield 72%; Mp 256–258ꢀC; IR
(KBR, v, cmꢁ1): 1620 (C¼¼O), 3435–3445 (NH); 1H NMR
(CDCl3) d: 1.95–2.40 (m, 6H, 3 ꢂ CH2), 5.25 (s, 1H, 4–H),
7.00–7.60 (m, 10H, ArHs), 7.65 (s, 1H, 50H), 9.80 (s, 1H,
NH), 10.65 (s, 1H, NH); 13C NMR d: 20.8, 34.2, 42.9, 45.8,
115.6, 118.5, 122.0, 125.4, 130.2, 135.8, 145.4, 155.2, 180.7,
199.8. Anal. Calcd. for C23H20N4O2: C, 71.87; H, 5.20; N,
14.58. Found: C, 71.79; H, 5.21; N, 14.53.
4-(p-Methylphenyl)-1,2,3,4,5,6,7,8-octahydroquinazoline-2-
thione (4a). Yield 75%; Mp 228–230ꢀC; IR (KBR, v, cmꢁ1):
1181 (C¼¼S), 3438–3445 (NH); 1H NMR (CDCl3) d: 1.62–
2.32 (m, 8H, 4 ꢂ CH2), 2.35 (s, 3H, CH3), 4.86 (s, 1H, 4–H),
7.02–7.20 (m, 4H, ArHs), 7.90 (bs, 1H, NH), and 10.7 (bs,
1H, NH). Anal. Calcd. for C15H18N2S: C, 69.76; H, 6.9; N,
10.85; S, 12.40. Found: C, 69.68; H, 7.1; N, 10.81; S, 12.20.
4-(3,4-Dimethoxyphenyl)-1,2,3,4,5,6,7,8-octahydroquinazo-
lin-2-one (40c). Yield 80%; Mp 252–254ꢀC; IR (KBR, v,
cmꢁ1): 1675 (C¼¼O), 3490–3443 (NH); 1H NMR (CDCl3) d:
1.70–2.25 (m, 8H, 4 ꢂ CH2), 3.72 (s, 3H, OCH3), 3.76 (s, 3H,
OCH3), 4.90 (s, 1H, 4–H), 7.10–7.25 (m, 3H, ArHs), 7.82 (bs,
1H, NH), and 10.2(bs, 1H, NH). Anal. Calcd. for C16H20N2O3:
C, 66.66; H, 6.94; N, 9.72. Found: C, 66.48; H, 6.96; N, 9.68.
4-(Indol-3-yl)-1,2,3,4,5,6,7,8-octahydroquinazolin-2-one
(40d). Yield 78%; Mp 255–257ꢀC; IR (KBR, v, cmꢁ1): 1670
1
(C¼¼O), 3490–3440 (NH); H NMR (CDCl3) d: 1.72–2.21 (m,
8H, 4 ꢂ CH2), 5.70 (s, 1H, 4–H), 7.7–8.10 (m, 5H, ArHs),
8.65 (s, 1H, exch. NH), 9.85 (s, 1H, NH), and 10.82 (s, 1H,
exch. NH). Anal. Calcd. for C16H17N3O: C, 71.91; H, 6.36; N,
15.73. Found: C, 71.72; H, 6.38; N, 15.79.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

332
P. Gupta, S. Gupta, A. Sachar, D. Kour, J. Singh, and R. L. Sharma
Vol 47
4-(1,3-Diphenyl-1H-pyrazol-4-yl)-1,2,3,4,5,6,7,8-octahy-
5-(4-Methylphenyl)-1,2,3,4,5,6,7,8-octahydropyrimido[4,5-
d]pyrimidine-2,4,7-trione (50c). Yield 77%; Mp 252–254ꢀC;
droquinazolin-2-one (40e). Yield 78%; Mp 264–266ꢀC; IR
(KBR, v, cmꢁ1): 1676 (C¼¼O), 3480–3440 (NH); 1H NMR
(CDCl3) d: 1.70–2.25 (m, 8H, 4 ꢂ CH2), 5.85 (s, 1H, 4–H),
7.10–8.20 (m, 11H, ArHs and 50H), 8.50 (s, 1H, exch. NH),
and 10.70 (s, 1H, exch. NH). Anal. Calcd. for C23H22N4O: C,
74.59; H, 5.94; N, 15.13. Found: C, 72.78; H, 5.95; N, 15.15.
5-Phenyl-7-thioxo-1,2,3,4,5,6,7,8-octahydropyrimido[4,5-
d]pyrimidine-2,4-dione (5a). Yield 72%; Mp 228–230ꢀC; IR
(KBR, v, cmꢁ1): 1178 (C¼¼S), 1665–1710 (C¼¼O), 3310–3450
(NH); 1H NMR (CDCl3) d: 5.20 (s, 1H, 5–H), 7.10–7.21 (m,
5H, ArHs), 8.82–8.98 (bs, 2H, NH at 1, 8), 9.56 (bs, 1H, NH
at 3), and 10.54 (bs, 1H, NH at 6). Anal. Calcd. for
C12H10N4O2S: C, 52.55; H, 3.64; N, 20.43; S, 11.67. Found:
C, 52.38; H, 3.60; N, 20.36; S, 11.61.
1
IR (KBR, v, cmꢁ1): 1685–1700 (C¼¼O), 3385–3420 (NH); H
NMR (CDCl3) d: 2.20 (s, 3H, CH3), 4.95 (s, 1H, 5–H), 6.90–
7.52 (m, 4H, ArHs), 8.85–9.00 (bs, 2H, NH at 1, 8), 9.58 (bs,
1H, NH at 3), and 10.50 (bs, 1H, NH at 6). Anal. Calcd. for
C13H12N4O3: C, 57.35; H, 4.41; N, 20.58. Found: C, 57.17; H,
4.42; N, 20.52.
5-(3,4-Dimethoxyphenyl)-1,2,3,4,5,6,7,8-octahydropyrimido[4,5-
d]pyrimidine-2,4,7-trione (50d). Yield 76%; Mp 270–272ꢀC; IR
(KBR, v, cmꢁ1): 1670–1705 (C¼¼O), 3330–3470 (NH); 1H
NMR (CDCl3) d: 3.72 (s, 3H, OCH3), 3.76 (s, 3H, OCH3),
4.90 (s, 1H, 5–H), 6.85–7.30 (m, 3H, ArHs), 8.98–9.30 (bs,
2H, NH at 1, 8), 9.58 (bs, 1H, NH at 3), and 10.58 (bs, 1H,
NH at 6). Anal. Calcd. for C14H14N4O5: C, 52.83; H, 4.40; N,
16.66. Found: C, 52.65; H, 4.42; N, 16.61.
5-(4-Methoxyphenyl)-7-thioxo-1,2,3,4,5,6,7,8-octahydropyri-
mido[4,5-d]pyrimidine-2,4-dione (5b). Yield 77%; Mp 232–
234ꢀC; IR (KBR, v, cmꢁ1): 1182 (C¼¼S), 1670–1708 (C¼¼O),
3410–3452 (NH); 1H NMR (CDCl3) d: 3.73 (s, 3H, OCH3),
5.30 (s, 1H, 5–H), 6.70–7.20 (m, 4H, ArHs), 8.72–9.12 (bs,
2H, NH at 1, 8), 9.62 (bs, 1H, NH at 3), and 10.55 (bs, 1H,
NH at 6); 13C NMR d: 47.4, 56.1, 85.7, 113.7, 126.4, 130.6,
142.6, 153.5, 155.8, 162.0, 165.5. Anal. Calcd. for
C13H12N4O3S: C, 51.31; H, 3.94; N, 18.42; S, 10.52. Found:
C, 51.12; H, 3.96; N, 18.33; S, 11.02.
Acknowledgment. The authors thank the Department of Chem-
istry, University of Jammu, Jammu, and IIIM, Jammu, for provid-
ing research and library facilities.
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