The synthesis of some new derivatives derived from 1,2,3,4- tetrahydrocyclohepteno[4,5]thieno-[2,3-d]pyrimidine

Article abstract of DOI:10.1080/10426500600865293

Polynuclear thieno[2,3-d]pyrimidone derivatives had been synthesized by an intermolecular reaction of 2-hydrazino-thieno[2,3-d]pyrimidin-4-one (1) with each of the aliphatic acids, and carbon disulfide afforded thienotriazolepyrimidin-5-one derivatives. O

Full text of DOI:10.1080/10426500600865293

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The Synthesis of
Some New Derivatives
Derived from 1,2,3,4-
Tetrahydrocyclohepteno[4,5]thieno
[2,3- d ]pyrimidine
A. S. Aly a , A. B. A. El-Gazzar a & H. A. R. Hussein a
a Photochemistry Departement (Heterocyclic Unit),
National Research Center, Dokki, Cairo, Egypt
Version of record first published: 01 Feb 2007.
To cite this article: A. S. Aly, A. B. A. El-Gazzar & H. A. R. Hussein
(2007): The Synthesis of Some New Derivatives Derived from 1,2,3,4-
Tetrahydrocyclohepteno[4,5]thieno-[2,3- d ]pyrimidine, Phosphorus, Sulfur, and
Silicon and the Related Elements, 182:1, 35-56
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Phosphorus, Sulfur, and Silicon, 182:35–56, 2007
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500600865293
The Synthesis of Some New Derivatives Derived
from 1,2,3,4-Tetrahydrocyclohepteno[4,5]thieno-
[2,3-d ]pyrimidine
A. S. Aly
A. B. A. El-Gazzar
H. A. R. Hussein
Photochemistry Departement (Heterocyclic Unit), National Research
Center, Dokki, Cairo, Egypt
Polynuclear thieno[2,3-d]pyrimidone derivatives had been synthesized by an in-
termolecular reaction of 2-hydrazino-thieno[2,3-d]pyrimidin-4-one (1) with each of
the aliphatic acids, and carbon disulfide afforded thienotriazolepyrimidin-5-one
derivatives. On the other hand, compound 1 that condensed with α-haloketone
yielded thienopyrimidotriazine, and with β-diketones and β-ketoesters formed 2-(1-
pyrazolyl) derivatives. Also, the condensation of compound 1 with aromatic aldehy-
des gave arylhydrazones. The purpose of synthesis the thienopyrimidine derivatives
is due to high biological activities. 4-chloro derivatives exhibited spasmodic and
antiviral activity, and also 4-amino derivatives showed antimicrobial, insecticidal,
pesticidal, and acaricidal activity.
Keywords 1H NMR spectra; azolopyrimidine; mass spectra; thienopyrimidine
DISCUSSION
Pyrimidines, being an integral part of nucleic acids and many
chemotherapeutic agents, display a wide range of pharmacologi-
cal activities as a phosphodiesterase inhibitor,1 fungicide,2 viricide,3
bactericide,4 and leishmanicide.5 This aroused considerable inter-
est to design and synthesize pyrimidines compounds profound leish-
manicidal activity. Sulfur-containing derivatives are important in
the pyrimidine chemistry because their different reactions make
them convenient intermediates.6,7 Among these reactions, the alky-
lation of mercaptopyrimidines is a very useful synthetic procedure
for the pyrimidine ring functionalization.8 2-hydrazinopyrimidine 1
can be synthesized by the nucleophilic displacement of the alkylthio
Received November 14, 2005; accepted May 3, 2006.
Address correspondence to A. S. Aly, National Research Center, Photochemistry
Department (Heterocyclic Unit), Dokki, Cairo, Egypt. E-mail: a s aly@yahoo.com
35

36
A. S. Aly et al.
group with hydrazine hydrate.9,10 Therefore, 2-hydrazinothieno[2,3-
d]pyrimidine is good source to synthesize several new
1
a
azolothienopyrimidines, thienopyrimido-as-triazines, and pyrazolyl-
thienopyrim-idines derivatives. Thus, heating under reflux 2-
hydrazino 1 with formic acid yielded 1H-cyclohepteno[4,5]thieno[2,3-
d][1,2,4]triazolo[4,3-a]pyrimidin-5(5H)-one (2).
1
Beside the correct values in elemental analyses, the IR, H NMR,
and mass spectra of 2 are in agreement with the assigned structure,
experimental (See Experimental Section).
Surprisingly, heating under reflux compound 1 with acetic acid
yielded the 2-acethydrazido derivative 3. The IR spectrum of 3 dis-
played absorption bands at 3277 cm−1, 3115 cm−1 2(NH) and 1680 and
1650 cm−1 2 (CO).
Compound
1
reacted with carbon disulphide in ethanolic
potassium hydroxide solution and afforded 3(3H)-thioxo-1,2-
dihydrocyclohepteno[4,5]thieno[2,3-d][1,2,4]triazolo[4,3-a]pyrimidin-
5(5H)-one (4).
The IR spectrum of 4 displayed absorption bands at 3404 cm−1, 3122
1
cm−1 2(NH), and 1664 cm−1 (CO). Its H NMR spectrum (DMSO-d6)
showed signals at δ 1.65 ppm (m, 4H, 2CH2), 1.85 (m, 2H, CH2), 2.90 (m,
2H, CH2), 3.20 (m, 2H, CH2), 12.65 (brs, 1H, NH, D2O exchangeable),
and 13.85 (brs, 1H, NH, D2O exchangeable). Mass spectra of 4 showed
the molecular ion peak at m/z 292.
It is reported in the literature that the cyclization of 2-hydrazino
derivatives with formic acid and carbon disulphide takes place at the
N-3 nitrogen atom11 to give azolo[4,3-a]-pyrimidines.
Also, 2-hydrazino derivative 1 was used for the preparation of
the thieno-pyrimidotriazine derivative, 5. Thus, heating under re-
flux compound 1 with chloroacetone in dry xylene yielded di-
rectly 3-methyl-1H,4H,6H-cycloheptenothieno-[2ꢀ,3ꢀ:4,5] pyrimido[2,1-
c][1,2,4]triazine-6-one (5). The previously discussed reaction may pro-
ceed via the intermediate (5ꢀ or 5ꢀꢀ), as shown in Scheme 1. Also the
2-hydrazino derivative 1 reacted with potassium thiocyanate in boiling
acetic acid to give compound 6. Beside the correct values in elemen-
tal analyses, the spectral data of 6 is in agreement with the assigned
structure, (c.f. Experimental section).
The 2-hydrazino derivative
1 reacted with β-ketoesters, β-
cyanoesters, and β-diketones to form 2-(1-pyrazolyl) derivatives. Thus,
heating under reflux compound 1 with ethyl acetoacetate afforded the
hydrazone derivative 7, which was cyclized by heating it in ethanolic
sodium hydroxide solution to give 8. Also, compound 8 can be achieved
directly from compound 1 by heating it with ethyl acetoacetate in
1
ethanolic sodium hydroxide solution. The H NMR spectrum (CDCl3)

The Synthesis of Some New Derivatives
37
of 7 showed signals at δ 1.25 ppm (t, 3H, CH3), 1.65 (m, 4H, 2CH2), 1.85
(m, 2H, CH2), 2.00 (s, 3H, CH3), 2.55 (m, 2H, CH2), 3.20 (m, 2H, CH2),
3.25 (s, 2H, CH2), 4.18 (q, 2H, CH2), 8.45 (brs, 1H, NH, D2O exchange-
able), and 9.55 (brs, 1H, NH, D2O exchangeable). Its 13C NMR spectrum
showed 9 sp3 and 8 sp2 carbon atoms, and its IR spectrum displayed ab-
sorption bands at 3279, 3206 cm−1 2(NH), 1741, and 1643 cm−1 2(CO).
1
Also, the H NMR spectrum (DMSO-d6) of 8 showed no signals corre-
sponding to ethyl group protons (see the Experimental section).
Compound 8 behaved typically as an active methylene containing
compounds. It coupled with aromatic diazonium salts to afford the cor-
responding azo derivatives 9a,b. The IR spectra of 9a displayed ab-
sorption bands around 3450 cm−1 (OH), 3180 cm−1 (NH) and 1656
1
cm−1 (CO). The H NMR spectrum (DMSO-d6) of 9a, as an example,
showed signals at δ 1.65 ppm (? m, 4H, 2CH2), 1.85 (m, 4H, 2CH2), 2.30
(s, 3H, CH3), 2.85 (m, 2H, CH2), 3.20 (m, 2H, CH2), 7.45 (d, 2H, aro-
matic protons), 7.75 (d, 2H, aromatic protons), 11.55 (brs, 1H, NH, D2O
exchangeable), and 13.00 (brs, 1H, OH, D2O exchangeable). Its mass
spectrum showed the molecular ion at peak m/z 454.
Similarly, 2-hydrazino derivative 1 reacted with ethyl cyanoacetate
in ethanolic sodium ethoxide solution to afford 2-(3-amino-5-hydroxy-
4H-pyrazol-l-yl) derivative 10. The IR spectrum of 10 displayed absorp-
tion bands at 3340 cm−1 (NH2), 3260 cm−1 (NH), and 1674 cm−1 (CO).
Its 1H NMR spectrum (DMSO-d6) showed signals at δ 1.65 ppm (m, 4H,
2CH2), 1.85 (m, 2H, CH2), 2.65 (m, 2H, CH2), 3.20 (m, 2H, CH2), (4.50–
5.40) (brs, 2H, NH2, D2O exchangeable), 7.95 (s, 1H, pyrazole proton),
and 8.25 (brs, 1H, NH, D2O exchangeable).
When equimolar amounts of 1 and pentane-2,4-dione or 3-chloro-
pentane-2,4-dione were heated under ruflux in absolute ethanol, 2-
pyrazolyl-thieno[2,3-d]pyrimidinone 11a,b were obtained in a good
yield. The 1H NMR spectrum (DMSO-d6) of 11a, as an example, showed
signals at δ 1.65 ppm (m, 4H, 2CH2), 1.85 (m, 2H, CH2), 2.30 (s, 3H,
CH3), 2.55 (s, 3H, CH3), 2.85 (m, 2H, CH2), 3.30 (m, 2H, CH2), 6.15 (s,
1H, CH), and 11.65 (brs, 1H, NH, D2O exchangeable). Its IR spectrum
displayed absorption bands at 3131 cm−1 (NH) and 1685 cm−1 (CO). Its
mass spectrum showed the molecular ion peak at m/z 314. Surprisingly,
heating compound 1 under reflux with 1,1,1-trifluoro-pentan-2,4-dione
in absolute ethanol led to the formation of compound 12. Beside the
correct values in elemental analyses, the spectral data of 12 is in agree-
ment with the assigned structure (see Experimental section).
Compound 1 gave arylhydrazone derivatives 13a–c when it was
treated with the appropriate aldehyde in boiling dioxane in the presence
of catalytic amounts of piperidine. Compounds 13a–c gave compatible

38
A. S. Aly et al.
spectral and analytical data (see Experimental section). Trials to cyclize
13 under different conditions had failed (Scheme 1).
On surveying the literature it is observed that publications
dealing with azolo[-,a]pyrimidines out number those of azolo[-
,c]pyrimidines. Therefore, we oriented our program to the syn-
thesis of azolo[-,c]thieno[3,2-c]pyrimidines. The reaction of the
S-methylthienopyrimidone 14 with phosphorus oxychloride, in dry
dioxane, yielded the corresponding 4-chloro derivative 15. The IR spec-
trum of 15 revealed the absence of any absorption bands in the carbonyl
region. Its 1H NMR spectrum (CDCl3) showed signals at δ 1.65 ppm (m,
4H, 2CH2), 1.75 (m, 2H, CH2), 2.58 (s, 3H, CH3), 2.86 (m, 2H, CH2), and
3.20 (m, 2H, CH2).
It is well known in pyrimidine chemistry that position 4 in pyrim-
idines and fused pyrimidines shows distinct activity toward nucle-
ophiles. Therefore, the chlorine atom at position 4 in compound 15 is
active. Its reactions with some nucleophiles, such as primary aromatic
amine, anthranilic acid, and hydrazine hydrate, were investigated.
Thus, heating under reflux compound 15 with aniline or p-toluidine, in
dry dioxane, afforded the 4-arylamine derivatives 16a,b. The IR spec-
trum of 16a displayed an absorption band around 3430 cm−1 (NH). The
1H NMR spectrum (CDCl3) of 16a, as an example, showed signals at
δ 1.85 ppm (m, 6H, 3CH2), 2.45 (s, 3H, CH3), 2.75 (m, 2H, CH2), 3.09
(m, 2H, CH2), 7.05 (t, 1H and 1H, NH, D2O exchangeable), 7.25 (t, 2H,
aromatic protons), and 7.55 (d, 2H, aromatic protons) (Scheme 2).
When 15 was fused with anthranilic acid at 180◦C, it gave 8-
methylthiocyclo-hepteno[4ꢀ,5ꢀ]thieno[2ꢀ,3ꢀ:4,5]pyrimido[6,1-b]quinazolin-
10-one (17). The IR spectrum of 17 revealed the absence of any
absorption bands in the (NH) region and displayed an absorption band
1
at 1690 cm−1 (CO). Its H NMR spectrum (CDCl3) showed signals at
δ 1.65 ppm (m, 4H, 2CH2), 1.85 (m, 2H, CH2), 2.45 (s, 3H, CH3), 2.85
(m, 2H, CH2), 3.70 (m, 2H, CH2), 7.45 (t, 1H, aromatic proton), 7.60 (d,
1H, aromatic proton), 7.65 (t, 1H, aromatic proton), and 8.25 (d, 1H,
aromatic proton).
The hydrazinepyrimidine 18 can be synthized by the nucleophilic
displacement of a labile halogen atom of the corresponding compound
15 by hydrazine hydrate. The IR spectrum of 18 displayed an absorption
band at 3283 cm−1 (NH). Its 1H NMR spectrum (CDCl3) showed signals
at δ 1.70 ppm (m, 4H, 2CH2), 1.85 (m, 2H, CH2), 2.56 (s, 3H, CH3), 2.80
(m, 2H, CH2), 2.97 (m, 2H, CH2), 4.15 (brs, 2H, NH2, D2O exchangeable),
and 6.57 (s, 1H, NH, D2O exchangeable).
The 4-hydrazino derivative 18 was used as a starting material for
the syntheses of some azolo[-,c]thieno[3,2-e]pyrimidines. Thus, heating
under reflux compound 18 with some aliphatic carboxylic acids,

The Synthesis of Some New Derivatives
39
O
NH
N
NHNH
2
S
1
O
O
NH
NH
N
N
N
HCOOH
AcOH
N
NH
NH
OCH
3
NH
N
O
S
S
S
S
N
O
S
S
2
3
Cl
S
CH
3
CS
2
Chloroacetone
NH
NH
N
O
NH
N
O
N
O
4
NH
2
CH
3
KSCN
AcOH
N
N
NH
N
O
NHNH
N
O
S
S
2
6
Ethyl acetoacetate
CH
3
NH
NH
N
CH
3
N
NH
N
O
NH
N
O
5
7
EtO
O
Ethyl cyanoacetate
NH
NH
N
N
N
N
N
O
N
O
S
S
CH
3
CH
3
8
10
O
diazonium salt
HO
NH
NH
Pentane-2,4-dione
N
N
N
N
HO
N
S
9a,b
CH
3
N
O
S
CH
3
11a,ba, X = H
Ar
H C
3
b, X = Cl
N
O
N
X
O
Trifloro -
pentane-
2,4-dione
H C
3
Aryl aldehyde
CF
3
NH
NH
N
N
Ar
NH
N
N
N
S
S
12
a, Ar = Phenyl
13a–c
b, Ar = p-Chlorophenyl
c, Ar = p-Methoxyphenyl
SCHEME 1

40
A. S. Aly et al.
O
NH
S
N
SCH3
14
POCl3
dry dioxane
Cl
N
S
N
SCH3
15
Ar-amine
anthranilic acid
N
N
HN
R
N
O
NH
S
SCH3
S
N
SCH3
16
17
a, R = H
b, R = Me
SCHEME 2
namely formic acid or acetic acid in the presence of catalytic amounts
of hydrochloric acid, yielded 3-alkyl-5-methylthiocyclohepteno-
[4,5]thieno[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine 19a,b. The IR spectra
of 19a,b revealed the absence of any absorption bands in the (NH)
region. The 1H NMR spectrum (CDCl3) of compound 19b, as an
example, showed signals at δ 1.75 ppm (m, 4H, 2CH2), 2.95 (m, 2H,
CH2), 2.65 (s, 3H, CH3), 2.85 (m, 2H, CH2), 3.15 (s, 3H, CH3), and
3.50 (m, 2H, CH2). Its mass spectrum showed the molecular ion peak
at m/z 304. Also, compound 18 reacted with carbon disulphide in
ethanolic potassium hydroxide solution to afford 5-methylthio-2H-
cyclohepteno[4,5]thieno[3,2-e][1,2,4]triazolo[4,3-c]pyrimi-dine-3(3H)-
1
thione (20). The H NMR spectrum (CDCl3) of compound 20 showed

The Synthesis of Some New Derivatives
41
signals at δ 1.65 ppm (m, 4H, 2CH2), 1.85 (m, 2H, CH2), 2.55 (s, 3H,
CH3), 2.85 (m, 4H, 2CH2), and 9.00 (brs, 1H, NH, D2O exchangeable).
Its mass spectrum showed the molecular ion peak at m/z 322.
The treatment of compound 18 with nitrous acid at 0◦C led to the
formation of 5-methylthiotetrazolo[1,5-c]cyclohepteno[4,5]thieno[3,2-
1
e]pyrimidine (21). The H NMR spectrum (CDCl3) of 21 showed sig-
nals at δ 1.75 ppm (m, 4H, 2CH2), 1.95 (m, 2H, CH2), 2.75 (s, 3H,
CH3), 2.95 (m, 2H, CH2), and 3.45 (m, 2H, CH2). The latter compound
was reduced into 4-amine-2-methylthiocyclohepteno[4,5]thieno[2,3-
1
d]pyrimidine (22) by zinc dust in acetic acid. The H NMR spectrum
(CDCl3) of compound 22 showed signals at δ 1.75 ppm (m, 4H, 2CH2),
1.96 (m, 2H, CH2), 2.55 (s, 3H, CH3), 2.85 (m, 2H, CH2), 2.95 (m, 2H,
CH2), and 5.30 (brs, 2H, NH2, D2O exchangeable). Its IR spectrum dis-
played an absorption band at 3494 cm−1 (NH2).
Surprisingly, when heating under reflux compound 18 with
chloroacetyl chloride in dry dioxane, it gave compound 23. The forma-
tion of 23 from the reactants may proceed as shown in Scheme 3. The
1H NMR spectrum (CDCl3) of compound 23 showed signals at δ 1.60
ppm (m, 4H, 2CH2), 1.75 (? m, 2H, CH2), 2.59( s, 3H, CH3), 2.70 (m, 2H,
CH2), 3.30 (m, 2H, CH2), and 5.15 (s, 2H, CH2). Its 13C NMR showed
7 SP3 and 7 SP2. Its mass spectrum showed the molecular ion peak at
m/z 338 (M+, 100%).
The reaction of 4-hydrazino derivative 18 with pentane-2,4-dione in
absolute ethanol led to the formation of 4-(3,5-dimethyl-1H-pyrazol-1-
yl)-2-methylthiocyclohepteno[4,5]thieno[2,3-d]pyrimidine (24). The 1H
NMR spectrum (CDCl3) of 24 showed signals at δ 1.65 ppm (m, 2H,
CH2), 1.70 (m, 2H, CH2), ?1.80 (m, 2H, CH2), ?2.15 (m, 2H, CH2), 2.25
(s, 3H, CH3), 2.40 (s, 3H, CH3), 2.59 (s, 3H, CH3), 2.90 (m, 2H, CH2), and
6.05 (s, 1H, pyrazolo proton). Its IR spectrum revealed the absence of
any absorption bands in the (NH) region. However, compound 18 gave
25 when it was heated with 1,1,1-Trifluoropentan-2,4-dione in absolute
ethanol. Beside the correct values in elemental analyses, the spectral
data (IR, 1H NMR, 13C NMR, and mass spectra) of 25 are in agreement
with the assigned structure (see Experimental section).
Finally, 4-hydrazino derivative 18 gave the corresponding arylhy-
drazone derivatives 26a–c, when it was treated with a proper aro-
matic aldehyde in boiling dioxane in the presence of catalytic amounts
of piperidine. The IR spectra of 26a–c displayed an absorption band
around 3320 cm−1 (NH). The 1H NMR spectrum (CDCl3) of 26a, as an
example, showed signals at δ 1.70 ppm (m, 4H, 2CH2), 1.85 (m, 2H,
CH2), 2.60 (s, 3H, CH3), 2.80 (m, 2H, CH2), 3.35 (m, 2H, CH2), 7.40 (m,
3H, aromatic protons), 7.70 (m, 2H, aromatic protons), and 8.35 (brs,
1H, NH, D2O exchangeable) (Scheme 3).

42
A. S. Aly et al.
NHNH2
N
S
N
SCH3
18
N
N
N
N
NH
CS2
N
R
N
S
AcOH
HCOOH
S
SCH3
S
N
N
SCH3
19
a, R = H
b, R = Me
20
N
N
N
N
HNO2
N
N
CH2Cl
SCH3
S
N
SCH3
S
N
Chloro-
acetyl
21
23
chlorid
NH
N
N
NH2
O
N
//
S
N
SCH3
S
N
SCH3
22
23
F3C
CH3
CH3
O
N
N
N
H3C
Trifloro -
pentane-
2,4-dione
N
N
HN
N
pentane-
2,4-dione
N
S
SCH3
S
SCH3
25
Aryl aldehyde
24
N
Ar
HN
H
N
S
N
SCH3
26a–c
a, Ar = phenyl
b, Ar = p-Chlorophenyl
c, Ar = p-Methoxyphenyl
SCHEME 3

The Synthesis of Some New Derivatives
43
EXPERIMENTAL
All melting points are uncorrected. Microanalyses were carried out at
the Microanalytical units, National Research Center and Faculty of
Science, Cairo University. IR spectra were carried out at a FT/IR-300
1
E Jasco using KBr discs. H NMR spectra were measured in DMSO
or CDCl3, using a JEOL-JNM-Ex270 NMR spectrometer. Mass spectra
were recorded on a Finnigan SSQ 7000 spectrometer. All reactions were
followed by TLC.
1H-cyclohepteno[4,5]thieno[2,3-d][1,2,4]triazolo[4,3-
a]pyrimidin-5 (5H)-one (2)
A mixture of compound 1 (2.50 g, 0.01 mole), formic acid (10 mL), and a
catalytic amount of concentrated hydrochloric acid solution was heated
under reflux for 6 h. The reaction mixture was allowed to cool to r.t.
and poured into water. The solid product so precipitated was filtered off
and recrystallized from dioxane to produce 2 as colorless crystals. IR
spectrum (KBr) cm−1: 3121 (NH), 2924 (CH aliphatic), and 1689 (CO).
1H NMR (DMSO-d6) δ ppm: 1.65 (m, 4H, 2CH2), 1.85 (m, 2H, CH2),
2.55 (m, 2H, CH2), 3.20 (m, 2H, CH2), 9.18 (s, 1H, CH), and 14.00 (s,
1H, NH, D2O exchangeable). MS (m/z): 260.0 (M+) 100%.
2-(Acethydrazido)-3H-cyclohepteno[4,5]thieno[2,3-
d]pyrimidin-4 (4H)-one (3)
A mixture of compound 1 (2.50 g, 0.01 mole) and glacial acetic acid
(30 mL) was refluxed for 5 h. The reaction mixture was allowed to cool
to r.t. and poured into water. The precipitate was collected by filtra-
tion, dried, and recrystallized from acetic acid to produce 3 as colorless
crystals. IR spectrum (KBr) cm−1: 3277 (NH), 3115 (NH), 2985 (CH
aliphatic) 1681 (CO) and 1651 (CO). 1H NMR (DMSO-d6) δ ppm: 1.65
(m, 4H, 2CH2), 1.75 (m, 2H, CH2), 1.85 (s, 3H, CH3), 2.55 (m, 2H, CH2),
3.20 (m, 2H, CH2), 8.55 (br s, 1H, NH, D2O exchangeable), 9.75 (br s, 1H,
NH, D2O exchangeable) and 11.20 (br s, 1H, NH, D2O exchangeable).
MS (m/z): 292.0 (M+) 100%.
3(3H)-Thioxo-1,2-dihydrocyclohepteno[4,5]thieno[2,3-
d][1,2,4]triazolo[4,3-a]pyrimidin-5(5H)-one (4)
To a warmed ethanolic sodium hydroxide solution [prepared by dissolv-
ing sodium hydroxide (0.40 g, 0.01 mole) in ethanol (50 mL)], compound
1 (2.50 g, 0.01 mole) and carbon disulphide (10 mL) was added. The

44
A. S. Aly et al.
TABLE I Physical Data for Products 2–26
Elemental Analyses Calcd./Found
Compound
No.
M.P. ◦
C
Yield (%)
67
M.F. (M. wt.)
C
H
N
S
2
238–240
melted
303–305
melted
?350
C12H12N4SO
(260.31)
55.36 4.64 21.52
55.56 4.82 21.39
53.40 5.51 19.16
54.00 5.00 19.00
12.31
12.30
—
3
65
60
68
65
70
60
70
65
63
70
70
60
70
75
78
65
65
70
60
70
65
C
13H16N4SO2
(292.35)
4
C
12H12N4S2O 49.29 4.13 19.16
—
dec
(292.38)
14H16N4SO
(288.37)
49.00 4.10 19.10
58.31 5.59 19.42
38.00 5.50 19.40
52.34 4.75 25.43
52.09 5.00 25.00
56.33 6.11 15.45
56.68 5.97 15.64
56.94 5.09 17.70
56.76 5.29 17.00
5
240–242
melted
294–296
melted
164–166
melted
?310
C
11.11
11.13
—
6
C
12H13N5SO
(275.33)
7
C17H22N4SO3
(362.45)
—
8
C
15H16N4SO2
(316.38)
10.13
10.12
—
9a
9b
10
11a
11b
12
13a
13b
13c
15
16a
16b
17
18
19a
270–272
melted
280–282
melted
290–292
melted
252–254
melted
244–246
melted
230–232
melted
310–312
dec
305–307
melted
289–291
melted
90–92
melted
177–179
melted
168–170
melted
193–195
melted
168–170
melted
185–187
melted
C21H19N6SO2Cl 55.44 4.20 18.47
(454.94)
22H22N6SO3
(450.52)
55.00 4.66 18.00
58.65 4.92 18.65
58.00 4.90 17.99
52.98 4.76 22.06
52.60 5.06 21.90
61.12 5.77 17.81
60.90 5.00 17.50
C
—
—
C
14H15N5SO2
(317.37)
C16H18N4SO
(314.41)
C
10.19
10.17
—
16H17N4SOCl 55.08 4.91 16.05
(348.85) 55.80 4.30 16.00
16H17N4SO2F3 49.47 4.43 14.50
C
—
—
—
(386.36)
18H18N4SO
(338.43)
49,90 4.80 14.00
63.88 5.36 16.55
63.96 5.57 16.36
C
C18H17N4SOCl 57.98 4.59 15.02
(372.85)
C19H20N4SO2
(368.45)
58.20 4.50 15.11
61.93 5.47 15.20
61.87 5.32 15.29
8.70
8.68
22.51
22.50
—
C
12H13N2S2Cl 50.60 4.60 9.83
(284.83)
18H19N3S2
(341.49)
50.80 4.40 9.80
63.30 5.60 12.30
63.06 5.78 12.22
64.18 5.95 11.81
63.90 5.95 11.73
C
C
19H21N3S2
(355.52)
—
—
—
—
C
19H18N3S2O 62.09 4.66 11.43
(367.49)
C12H16N4S2
(280.41)
61.80 4.83 11.19
51.40 5.75 19.97
51.60 5.50 19.22
53.76 4.85 19.29
53.35 5.00 19.14
C
13H14N4S2
(290.40)
(Continued)

The Synthesis of Some New Derivatives
45
TABLE I Physical Data for Products 2–26 (Continued)
Elemental Analyses Calcd./Found
Compound
No.
M.P. ◦
C
Yield(%)
75
M.F. (M. wt.)
C
H
N
S
19b
20
151–153
melted
190–192
melted
165–167
melted
177–179
melted
214–216
melted
119–121
melted
124–126
melted
145–147
melted
C14H16N4S2
(304.43)
55.23 5.29 18.40
55.50 4.90 18.00
48.42 4.37 17.37
48.00 4.00 17.00
49.46 4.49 24.03
49.94 4.43 24.22
54.30 5.69 15.83
54.33 5.76 15.72
—
68
60
69
70
65
77
80
75
70
C
C
C
13H14N4S3
(322.47)
12H13N5S2
(291.39)
12H15N3S2
(265.40)
29.82
29.80
22.00
22.00
24.16
24.15
—
21
22
23
C14H15N4S2Cl 49.61 4.45 16.52
(338.93)
C17H20N4S2
(344.50)
50.49 4.68 16.71
59.27 5.85 16.26
59.54 5.71 16.37
24
—
—
—
—
—
25
C17H19N4S2OF3 49.02 4.59 13.45
(416.48)
19H20N4S2
(368.52)
49.24 4.50 13.47
61.92 5.47 15.20
62.70 5.00 15.00
26a
26b
26c
C
177–179
melted
150–152
melted
C
19H19N4S2Cl 56.63 4.75 13.90
(402.96) 56.80 4.35 13.80
20H22N4S2O 60.27 5.56 14.05
(398.55) 60.49 5.70 14.00
C
mixture was heated on a water bath at 80◦C under reflux for 10 h, it
was poured into water and neutralized by diluted acetic acid, and the
formed precipitate was filtered off. The product was recrystallized from
dioxane to produce 4 as yellow crystals. IR spectrum (KBr) cm−1: 3404
(NH), 3122 (NH), 2929 (CH aliphatic) and 1664 (CO). 1H NMR (DMSO-
d6) δ ppm: 1.65 (m, 4H, 2CH2), 1.85 (m, 2H, CH2), 2.90 (m, 2H, CH2),
3.20 (m, 2H, CH2), 12.65 (brs, 1H, NH, D2O exchangeable) and 13.85
(brs, 1H, NH, D2O exchangeable). MS (m/z): 292 (M+) 100%.
3-Methyl-1H-cyclohepteno[4ꢀ,5ꢀ]thieno[2ꢀ,3ꢀ:4,5]pyrimido[2,1-
c][1,2,4]triazin-(4H)-5(5H)-one (5)
A mixture of compound 1 (2.50 g, 0.01 mole) and chloroacetone (0.93 g,
0.01 mole) was heated under reflux for 6 h in dry xylene (30 mL). The
solid product so precipitated was filtered off and recrystallized from
dioxane to produce 5 as yellow crystals. IR spectrum (KBr) cm−1: 3373
(NH), 2918 (CH aliphatic) and 1688 (CO). 1H NMR (DMSO-d6) δ ppm:
1.65 (m, 4H, 2CH2), 1.85 (m, 2H, CH2), 2.30 (m, 2H, CH2), 2.65 (m, 2H,
CH2), 2.85 (s, 3H, CH3), 3.15 (m, 2H, CH2) and 10.25 (brs, 1H, NH, D2O
exchangeable). MS (m/z): 288(M+) 64.19%, 273 (M-Me) 17.84%.

46
A. S. Aly et al.
3-Amino-1H-cyclohepteno[4,5]thieno[2,3-
d][1,2,4]triazolo[4ꢀ,3ꢀ-a]pyrimidin-5(5H)-one (6)
A mixture of compound 1 (2.50 g, 0.01 mole) and potassium thiocyanate
(0.97 g, 0.01 mole) was heated under reflux in acetic acid for 6 h. The
reaction mixture was allowed to cool to r.t. and poured into water. The
precipitate so-formed was collected by filtration, dried, and recrystal-
lized from acetic acid to produce 6 as colorless crystals. IR spectrum
1
(KBr) cm−1: 3284 (NH) and 1653 (CO). H NMR (DMSO-d6) δ ppm:
1.65 (m, 4H, 2CH2), 1.85 (m, 2H, CH2), 2.65 (m, 2H, CH2), 3.20 (m, 2H,
CH2), 8.85 (brs, 1H, NH, D2O exchangeable) and 9.90 (brs, 1H, NH,
D2O exchangeable).
2-Ethylacetoacetatehydrazon-3H-cyclohepteno[4,5]thieno[2,3-
d]pyrimidin-4(4H)-one (7)
A mixture of compound 1 (2.50 g, 0.01 mole) and ethyl acetoacetate
(1.30 g, 0.01 mole) was heated under reflux in absolute ethanol for 5 h.
The reaction mixture was allowed to cool to r.t. and poured into water.
The precipitate so-formed was collected by filtration, dried and recrys-
tallized from ethanol to produce 7 as colorless crystals. IR spectrum
(KBr) cm−1: 3279 (NH), 3206 (NH), 2975 (CH aliphatic), 1741 (CO) and
1
1643 (CO). H NMR (CDCl3) δ ppm: 1.25 (m, 3H, CH3), 1.65 (m, 4H,
2CH2), 1.85 (m, 2H, CH2), 2.00 (s, 3H, CH3), 2.55 (m, 2H, CH2), 3.20 (m,
2H, CH2), 3.25 (s, 2H, CH2), 4.15 (q, 2H, CH2), 8.45 (brs, 1H, NH, D2O
exchangeable), and 9.55 (brs, 1H, NH, D2O exchangeable). 13C NMR
(CDCl3) δ ppm: 14.1, 15.9, 24.2, 27.2, 27.8, 29.5, 32.4, 44.0, 61.2 (seven
CH2 + Two CH3); 117.5, 132.1, 136.5, 146.2, 148.9 and 158.6 (thieno
pyrimidine carbon atoms); 163.6 and 169.4 (two CO). MS (m/z): 362.1
(M+) 47.70%, 316 (M-EtOH) 12.00%.
2-(3-Methyl-5-oxo-4H-pyrazol-1-yl)-3H-
cyclohepteno[4,5]thieno[2,3-d]pyrimidin-4(4H)-one (8)
Method A
A solution of compound 1 (2.50 g, 0.01 mole) and ethyl acetoac-
etate (1.30 g, 0.01 mole) in sodium ethoxide solution [prepared by
dissolving sodium metal (0.23 g, 0.01 mole) in absolute ethanol (30
mL)] was heated under reflux for 5 h. The reaction mixture was al-
lowed to cool to r.t., poured into water, and neutralized by diluted
acetic-acid solution. The solid product so-precipitated was filtered off,
dried, and recrystallized from dimethylformamide to produce 8 as col-
orless crystals.

The Synthesis of Some New Derivatives
47
Method B
A solution of compound 7 (3.62 g, 0.01 mole) was heated under reflux
with sodium ethoxide solution [prepared by dissolving sodium metal
(0.23 g, 0.01 mole) in absolute ethanol (30 mL)] for 5 h. The reaction
mixture was allowed to cool to r.t. and poured into water and neutralized
by diluted acetic-acid solution .The precipitate so-formed was collected
by filtration, dried, and recrystallized from dimethylformamide to pro-
duce 8 as colorless crystals. IR spectrum (KBr) cm−1: 3446 (OH), 2922
1
(CH aliphatic), and 1654 (CO). H NMR (CDCl3-TFA) δ ppm: 1.65 (m,
4H, 2CH2), 1.85 (m, 2H, CH2), 2.35 (s, 3H, CH3), 2.75 (m, 2H, CH2),
3.15 (m, 2H, CH2), and 5.55 (s, 1H, CH). MS (m/z): 316 (M+) 100%, 301
(M-Me) 15.90%.
Coupling 8 with Aryldinediazonium Salts: The Preparation
of 9a,b
To an ice-cold solution of the appropriate aromatic amine (0.01 mole) in
[-38pt]Au: Colon ok? concentrated hydrochloric acid (3 mL) was added
dropwise a solution of sodium nitrite (1.03 g, 0.01 mole) dissolved in
the least amount of water, in an ice bath at −5◦C. This previously pre-
pared diazonium salt was added dropwise to a mixture of 8 (3.16 g, 0.01
mole) and anhydrous sodium acetate in ethanol. The reaction mixture
was allowed to stand overnight at r.t., and then it was poured into wa-
ter. The formed solid was filtered off, washed with water, dried, and
recrystallized from dioxane to produce 9a,b.
Coupling 8 with Diazotized-4-chloroaniline: The Preparation
of 9a
Compound 9a was obtained from compound 8 (3.16 g, 0.01 mole) and
diazotized-4-chloroaniline (1.27 g, 0.01 mole). The product was recrys-
tallized from dioxane to produce 9a as orange crystals. IR spectrum
(KBr) cm−1: 3450 (OH), 3180 (NH), 2913 (CH aliphatic) and 1656 (CO).
1H NMR (DMSO-d6) δ ppm: 1.65 (m, 4H, 2CH2), 1.85 (m, 2H, CH2),
2.30 (s, 3H, CH3), 2.85 (m, 2H, CH2), 3.20 (m, 2H, CH2), 7.45 (d, 2H,
aromatic protons), 7.75 (d, 2H, aromatic protons), 11.55 (br s, 1H, NH,
D2O exchangeable) and 13.00 (br s, 1H, OH, D2O exchangeable). MS
(m/z): 454 (M+) 100%.
Coupling 8 with Diazotized-4-methoxyaniline:
The Preparation of 9b
Compound 9b was obtained from compound 8 (3.16 g, 0.01 mole)
and diazotized-4-methoxyaniline (1.13 g, 0.01 mole). The product was

48
A. S. Aly et al.
recrystallized from dioxane to produce 9b as orange crystals. IR spec-
trum (KBr) cm−1: 3443 (OH), 3212 (NH), 2920 (CH aliphatic) and 1660
(CO). 1H NMR (DMSO-d6) δ ppm: 1.65 (m, 4H, 2CH2), 1.7 (m, 2H, CH2),
2.4 (s, 3H, CH3), 2.9 (m, 2H, CH2), 3.2 (m, 2H, CH2), 3.8 (s, 3H, CH3),
7.0 (d, 2H, aromatic protons), 7.7 (d, 2H, aromatic protons), 11.6 (br s,
1H, NH, D2O exchangeable) and 13.2 (brs, 1H, OH, D2O exchangeable).
MS (m/z): 450 (M+) 100%.
2-(3-Amino-5-oxo-4H-pyrazol-1-yl)-3H-
cyclohepteno[4,5]thieno[2,3-d]pyrimidine-4(4H)-one (10)
To a warmed ethanolic sodium ethoxide solution [prepared by dissolv-
ing sodium metal (0.23 g, 0.01 mole) in absolute ethanol (30 mL)] was
added compound 1 (2.50 g, 0.01 mole) and ethyl cyanoacetate (1.13 g,
0.01 mole). The heating was continued for 5 h. The reaction mixture
was allowed to cool to r.t., poured into water, and neutralized by di-
luted acetic acid solution. The solid product so precipitated was filtered
off, dried, and recrystallized from dimethylformamide to produce 10 as
yellow crystals. IR spectrum (KBr) cm−1: 3340 (NH2), 3260 (NH), 2975
(CH aliphatic) and 1674 (CO). 1H NMR (DMSO-d6) δ ppm: 1.65 (m, 4H,
2CH2), 1.85 (m, 2H, CH2), 2.65 (m, 2H, CH2), 3.20 (m, 2H, CH2), 4.50–
5.40 (br, 2H, NH2, D2O exchangeable), 8.95 (s, 1H, CH), and 8.25 (br,
1H, NH, D2O exchangeable).
2-(3-Methyl-4-(un)substituted-5-substituted-pyrazol-1-yl)-3H-
cyclohepteno[4,5]-thieno[2,3-d]pyrimidin-4(4H)-one (11a,b):
General Procedure
A mixture of compound 1 (2.50 g, 0.01 mole) and the appropriate β-
diketone (0.01 mole) was heated under reflux in absolute ethanol (30
mL) for 5 h. The reaction mixture was allowed to cool to r.t. The pre-
cipitate solid was collected by filtration, dried, and recrystallized from
dioxane to produce 11a,b.
2-(3,5-Dimethyl-pyrazol-1-yl)-3H-cyclohepteno[4,5]thieno[2,3-
d]pyrimidin-4(4H)-one (11a)
Compound 11a was obtained from compound 1 (2.50 g, 0.01 mole) and
pentane-2,4-dione (1.00 g, 0.01 mole). The product was recrystallized
from dioxane to produce 11a as pale yellow crystals. IR spectrum (KBr)
cm−1: 3131 (NH), 2919 (CH aliphatic) and 1685 (CO). 1H NMR (DMSO-
d6) δ ppm: 1.65 (m, 4H, 2CH2), 1.85 (m, 2H, CH2), 2.30 (s, 3H, CH3),
2.55 (s, 3H, CH3), 2.85 (m, 2H, CH2), 3.30 (m, 2H, CH2), 6.15 (s, 1H, CH)
and 11.65 (brs, 1H, NH, D2O exchangeable). MS (m/z): 314 (M+) 100%.

The Synthesis of Some New Derivatives
49
2-(3,5-Dimethyl-4-chloropyrazol-1-yl)-3H-
cyclohepteno[4,5]thieno[2,3-d]pyrimi-din-4(4H)-one (11b)
Compound 11b was obtained from compound 1 (2.50 g, 0.01 mole) and
3-chloropentane-2,4-dione (1.34 g, 0.01 mole). The product was recrys-
tallized from dioxane to produce 11b as orange crystals. IR spectrum
1
(KBr) cm−1: 3124 (NH), 2920 (CH aliphatic) and 1683 (CO). H NMR
(DMSO-d6) δ ppm: 1.65 (m, 4H, 2CH2), 1.85 (m, 2H, CH2), 2.35 (s, 3H,
CH3), 2.55 (s, 3H, CH3), 2.85 (m, 2H, CH2) and 3.25 (m, 2H, CH2). MS
(m/z): 348 (M+) 100%.
2-(1,1,1-Trifluoropentane-2,4-dione-hydrazone)-3H-
cyclohepteno[4,5]thieno[2,3-d]pyrimidin-4(4H)-one (12)
A mixture of compound 1 (2.50 g, 0.01 mole) and 1,1,1-trifluoro-2,4-
pentandione (1.54 g, 0.01 mole) was heated under reflux in absolute
ethanol (30 mL) for 5 h. The reaction mixture was allowed to cool to
r.t. The precipitated solid was collected by filtration, dried, and recrys-
tallized from dioxane to produce 12 as pale yellow crystals. IR spec-
1
trum (KBr) cm−1: 3110 (NH), 2925 (CH aliphatic) and 1670 (CO). H
NMR (DMSO-d6) δ ppm: 1.65 (m, 4H, 2CH2), 1.85 (m, 2H, CH2), 2.15
(s, 3H, CH3), 2.75 (m, 2H, CH2), 3.15 (m, 2H, CH2), 3.30–3.65 (m, 2H,
CH2), 8.00 (s, 1H, NH, D2O exchangeable) and10.80 (s, 1H, NH, D2O
exchangeable). MS (m/z): 386 (M+) 100%.
2-(Arylmethylenehydrazone)-3H-cyclohepteno[4,5]thieno[2,3-
d]pyrimidin-4(4H)-one (13a–c): General Procedure
A mixture of compound 1 (2.50 g, 0.01 mole) and the appropriate aro-
matic aldehyde (0.01 mole), dioxane (30 mL), and a catalytic amount of
piperidine were heated under reflux for 6 h. The reaction mixture was
allowed to cool to r.t., and then it was poured into water. The formed
precipitate was filtered off, washed with water, dried, and recrystallized
from dimethylformamide to produce 13a,b.
2-(Phenylmethylenehydrazone)-3H-
cyclohepteno[4,5]thieno[2,3-d]pyrimidin-4(4H)-one (13a)
Compound 13a was obtained from compound 1 (2.50 g, 0.01 mole) and
benzaldehyde (1.06 g, 0.01 mole). The product was recrystallized from
dimethylformamide to produce 13a as pale yellow crystals. IR spec-
trum (KBr) cm−1: 3375 (NH), 3140 (NH), 3044 (CH aromatic), 2919
(CH aliphatic) and 1667 (CO). 1H NMR (DMSO-d6) δ ppm: 1.65 (m, 4H,
2CH2), 1.85 (m, 2H, CH2), 2.65 (m, 2H, CH2), 3.15 (m, 2H, CH2), 7.35

50
A. S. Aly et al.
(m, 3H, aromatic protons), 7.85 (m, 2H, aromatic protons), 8.00 (s, 1H,
CH), 11.25 (brs, 1H, NH, D2O exchangeable), and 11.55 (br s, 1H, NH,
D2O exchangeable). MS (m/z): 338.20 (M+) 100%.
2-(4-Chlorophenylmethylenehydrazone)-3H-
cyclohepteno[4,5]thieno[2,3-d]pyrimidin-4(4H)-one (13b)
Compound 13b was obtained from compound 1 (2.50 g, 0.01 mole) and 4-
chlorobenzaldehyde (1.40 g, 0.01 mole). The product was recrystallized
from dimethylform-amide to produce 13b as yellow crystals. IR spec-
trum (KBr) cm−1: 3375 (NH), 3140 (NH), 3044 (CH aromatic), 2920
1
(CH aliphatic) and 1668 (CO). H NMR (DMSO-d6) δ ppm: 1.65 (m,
4H, 2CH2), 1.85 (m, 2H, CH2), 2.75 (m, 2H, CH2), 3.15 (m, 2H, CH2),
7.50 (d, 2H, aromatic protons), 8.00 (t, 3H, aromatic protons + CH),
11.35 (br s, 1H, NH, D2O exchangeable), and 11.65 (br s, 1H, NH, D2O
exchangeable). MS (m/z): 372 (M+) 100%.
2-(4-Methoxyphenylmethylenehydrazone)-3H-
cyclohepteno[4,5]thieno[2,3-d]pyrimidin-4(4H)-one (13c)
Compound 13c was obtained from compound 1 (2.50 g, 0.01 mole) and
4-methoxybenzaldehyde (1.36 g, 0.01 mole). The product was recrys-
tallized from dimethylformamide to produce 13c as yellow crystals. IR
spectrum (KBr) cm−1: 3376 (NH), 3163 (NH), 3045 (CH aromatic), 2919
(CH aliphatic) and 1667 (CO). 1H NMR (DMSO-d6) δ ppm: 1.65 (m, 4H,
2CH2), 1.85 (m, 2H, CH2), 2.65 (m, 2H, CH2), 3.20 (m, 2H, CH2), 3.80 (s,
3H, CH3), 6.85 (d, 2H, aromatic protons), 7.90 (d, 2H, aromatic protons),
8.00 (s, 1H, CH), 11.15 (br s, 1H, NH, D2O exchangeable) and 11.50 (brs,
1H, NH, D2O exchangeable). 13C NMR (DMSO-d6) δ ppm: 27.0, 27.3,
27.6, 28.9, 32.1 and 55.3 (5 CH2 + OCH3); 114.0, 116.1, 127.0, 129.0,
129.8, 136.0, 142.9, 149.7, 158.8 and 160.8 (thienopyrimidine aromatic
carbon atoms); 163.8 (CO). MS (m/z): 368.20 (M+) 100%.
4-Chloro-2-methylthio–cyclohepteno[4,5]thieno[2,3-
d]pyrimidine (15)
A solution of compound 14 (2.66 g, 0.01 mole) in dry dioxane was treated
with phosphorus oxychloride (9 mL) and stirred under reflux for 3 h.
The reaction mixture was allowed to cool to r.t. and poured into cold wa-
ter. The solid product so precipitated was filtered off and recrystallized
from absolute ethanol to produce 15 as colorless crystals. IR spectrum
(KBr) cm−1: 2996 (CH aliphatic), 1554 (C N) and 1467 (C C). 1H NMR
(CDCl3) δ ppm: 1.65 (m, 4H, 2CH2), 1.75 (m, 2H, CH2), 2.58 (s, 3H,

The Synthesis of Some New Derivatives
51
CH3), 2.85 (m, 2H, CH2) and 3.20 (m, 2H, CH2)..MS (m/z): 284.0 (M+)
100%.
4-Arylamino-2-methylthio-cyclohepteno[4,5]thieno[2,3-
d]pyrimidine (16a,b): General Procedure
An equimolar amount of 15 (2.84 g, 0.01 mole) and the appropriate
aromatic amine (0.01 mole) were heated under reflux in dry dioxane for
6 h. The solid that separated during reflux was collected by filtration,
washed, dried, and recrystallized from ethanol to produce 16a,b.
2-Methylthio-4-phenylamino-cyclohepteno[4,5]thieno[2,3-
d]pyrimidine (16a)
Compound 16a was obtained from compound 15 (2.84 g, 0.01 mole) and
aniline (0.93 g, 0.01 mole). The product was recrystallized from ethanol
to produce 16a as colorless crystals. IR spectrum (KBr) cm−1: 3436
1
(NH), 3028 (CH aromatic), and 2963 (CH aliphatic). H NMR (CDCl3)
δ ppm: 1.85 (m, 6H, 3CH2), 2.45 (s, 3H, CH3), 2.75 (m, 2H, CH2), 3.09
(m, 2H, CH2), 7.05 (t, 1H, CH and 1H, NH, D2O exchangeable), 7.25
(t, 2H, aromatic protons) and 7.55 (d, 2H, aromatic protons). MS (m/z):
341 (M+) 100%.
2-Methylthio-4-(4-methylphenylamino)-
cyclohepteno[4,5]thieno[2,3-d]pyrimidine (16b)
Compound 16b was obtained from compound 15 (2.84 g, 0.01 mole) and
4-methylaniline (1.07 g, 0.01 mole). The product was recrystallized from
ethanol to produce 16b as colorless crystals. IR spectrum (KBr) cm−1
:
1
3437 (NH) and 2909 (CH aliphatic). H NMR (CDCl3) δ ppm: 1.65 (m,
4H, 2CH2), 1.85 (m, 2H, CH2), 2.40 (s, 3H, CH3), 2.50 (s, 3H, CH3), 2.80
(m, 2H, CH2), 3.25 (m, 2H, CH2), 7.15 (d, 2H, aromatic protons), 7.65
(d, 2H, aromatic protons) and 8.85 (brs, 1H, NH, D2O exchangeable).
MS (m/z): 355 (M+) 100%.
8-Methylthio-cyclohepteno[4,5]thieno[2ꢀ,3ꢀ:4,5]pyrimido[6,1-
b]quinazolin-10-one (17)
A mixture of compound 15 (2.84 g, 0.01 mole) and anthranilic acid
(1.37 g, 0.01 mole) was fused at 170–180◦C for 3 h. Cooling and an
addition of methanol solidified the product. The precipitate so formed
was collected by filtration and recrystallized from dioxane to produce
17 as yellow crystals. IR spectrum (KBr) cm−1: 2922 (CH aliphatic) and

52
A. S. Aly et al.
1
1690 (CO). H NMR (CDCl3) δ ppm: 1.65 (m, 4H, 2CH2), 1.85 (m, 2H,
CH2), 2.45 (s, 3H, CH3), 2.85 (m, 2H, CH2), 3.70 (m, 2H, CH2), 7.45
(t, 1H, aromatic proton), 7.60 (d, 1H, aromatic proton), 7.65 (t, 1H, aro-
matic proton) and 8.25 (d, 1H, aromatic proton). MS (m/z): 367.10 (M+)
100%, 339 (M-CO) 39.52.
4-Hydrazino-2-methylthio-cyclohepteno[4,5]thieno[2,3-
d]pyrimidine (18)
A mixture of compound 15 (2.84 g, 0.01 mole) and hydrazine hydrate
(99–100%) (7 mL, 0.03 mole) in dioxane (30 mL) and ethanol (5 mL) was
heated under reflux for 5 h. The reaction mixture was allowed to cool
to r.t. The precipitated solid was collected by filtration, washed, dried,
and recrystallized from ethanol to produce 18 as colorless crystals. IR
spectrum (KBr) cm−1: 3283 (NH), 3186 (NH) and 2986 (CH aliphatic).
1H NMR (CDCl3) δ ppm: 1.70 (m, 4H, 2CH2), 1.85 (m, 2H, CH2), 2.55
(s, 3H, CH3), 2.80 (m, 2H, CH2), 3.95 (m, 2H, CH2), 4.15 (brs, 2H, NH2,
D2O exchangeable) and 6.55 (br s, 1H, NH, D2O exchangeable). 13C
NMR (CDCl3) δ ppm: 14.1 (CH3); 26.4, 27.0, 28.9, 29.8, and 30.7 (Five
CH2); 113.5, 130.2, 135.4, 158.3, 164.7, and 164.8 (thienopyrimidine
carbon atoms). MS (m/z): 280 (M+) 100%.
5-Methylthio-Cyclohepteno[4,5]thieno[3,2-
e][1,2,4]triazolo[4ꢀ,3ꢀ-c]pyrimidine (19a)
A mixture of compound 18 (2.80 g, 0.01 mole), formic acid (10 mL)
and a catalytic amount of concentrated hydrochloric acid was heated
under reflux for 6 h. The reaction mixture was allowed to cool to r.t.
and poured into water. The solid product so precipitated was filtered
off, dried, and recrystallized from dioxane to produce 19a as colorless
crystals. IR spectrum (KBr) cm−1: 2919 (CH aliphatic) and 1488 (C C).
1H NMR (CDCl3) δ ppm: 1.75 (m, 4H, 2CH2), 1.95 (m, 2H, CH2), 2.75 (s,
3H, CH3), 2.85 (m, 2H, CH2), 3.40 (m, 2H, CH2) and 8.75 (s, 1H, CH).
MS (m/z): 290.0(M+) 100%.
3-Methyl-5-methylthio-cyclohepteno[4,5]thieno[3,2-
e][1,2,4]triazolo[4ꢀ,3ꢀ-c]pyrimidine (19b)
A solution of compound 18 (2.80 g, 0.01 mole) in glacial acetic acid
(50 mL) was heated under reflux for 6 h. The reaction mixture was
allowed to cool to r.t. and poured into water. The solid product so pre-
cipitated was filtered off, dried and recrystallized from acetic acid to
produce 19b as colorless crystals. IR spectrum (KBr) cm−1: 2994 (CH

The Synthesis of Some New Derivatives
53
1
aliphatic). H NMR (CDCl3) δ ppm: 1.75 (m, 4H, 2CH2), 2.95 (m, 2H,
CH2), 2.65 (s, 3H, CH3), 2.80 (m, 2H, CH2), 3.15 (s, 3H, CH3), and 3.50
(m, 2H, CH2). MS (m/z): 304 (M+) 100%, 289 (M-Me) 40.05%.
5-Methylthio-2H-cyclohepteno[4,5]thieno[3,2-
e][1,2,4]triazolo[4ꢀ,3ꢀ-c]pyrimidine-3(3H)-thione (20)
To a warmed ethanolic sodium hydroxide solution [prepared by dissolv-
ing sodium hydroxide (0.40 g, 0.01 mole) in ethanol (50 mL)], compound
18 (2.80 g, 0.01 mole) and carbon disulphide (10 mL) were added. The
mixture was heated on a water bath at 80◦C under reflux for 10 h, and
then it was poured into water, neutralized by diluted acetic acid. The
formed precipitate was filtered off. The product was recrystallized from
dioxane to produce 20 as yellow crystals. IR spectrum (KBr) cm−1: 3420
(NH), 2922 (CH aliphatic). 1H NMR (CDCl3) δ ppm: 1.65 (m, 4H, 2CH2),
1.85 (m, 2H, CH2), 2.55 (s, 3H, CH3), 2.85 (m, 4H, 2CH2) and 9.00 (brs,
1H, NH, D2O exchangeable).
5-Methylthiotetrazolo[1,5-c]cyclohepteno[4,5]thieno[3,2-
e]pyrimidine (21)
To an ice-cold solution of compound 18 (2.80 g, 0.01 mole) in acetic acid
(10 mL), a solution of sodium nitrite [prepared by dissolving sodium
nitrite (1.03 g, 0.01 mole) in the least amount of water] was added drop-
wise in an ice bath at –5◦C. The reaction mixture was allowed to stand
overnight at r.t., and then it was poured into water. The formed solid was
filtered off, washed with water, dried, and recrystallized from ethanol
to produce 21. IR spectrum (KBr) cm−1: 2921 (CH aliphatic). 1H NMR
(CDCl3) δ ppm: 1.75 (m, 4H, 2CH2), 1.95 (m, 2H, CH2), 2.75 (s, 3H, CH3),
2.95 (m, 2H, CH2) and 3.45 (m, 2H, CH2). MS (m/z): 291(M+) 71.38%.
4-Amino-2-methylthio-cyclohepteno[4,5]thieno[2,3-
d]pyrimidine (22)
A mixture of compound 21 (2.91 g, 0.01 mole), zinc dust (0.65 g, 0.01
mole), and acetic acid (10 mL) was stirred at r.t. for 2 h, and then it
was heated on a water bath at 80◦C for 6 h (under TLC control). The
reaction mixture was then extracted with benzene. Then benzene was
evaporated, and the formed solid was recrystallized from methanol to
produce 22 as pale yellow crystals. IR spectrum (KBr) cm−1: 3494 (NH2)
and 2924 (CH aliphatic). 1H NMR (CDCl3) δ ppm: 1.75 (m, 4H, 2CH2),
1.95 (m, 2H, CH2), 2.55 (s, 3H, CH3), 2.85 (m, 2H, CH2), 2.95 (m, 2H,
CH2) and 5.30 (brs, 2H, NH2, D2O exchangeable). MS (m/z): 265 (M+)
100%.

54
A. S. Aly et al.
3-Chloromethyl-5-methylthio-cyclohepteno[4,5]thieno[3,2-
e][1,2,4]triazolo[4,3-c]pyrimidine (23)
A mixture of compound 18 (2.80 g, 0.01 mole), chloroacetyl chloride
(1.13 g, 0.01 mole), was allowed to stand overnight at r.t. in 20 ml of
dry dioxane. The solid so formed was filtered, dried, and recrystallized
from dioxane to produce 23 as colorless crystals. IR spectrum (KBr)
cm−1: 2994 (CH aliphatic). 1H NMR (CDCl3) δ ppm: 1.60 (m, 4H, 2CH2),
1.75 (m, 2H, CH2), 2.55 (s, 3H, CH3), 2.70 (m, 2H, CH2), 3.30 (m, 2H,
CH2) and 5.15 (s, 2H, CH2). 13C NMR (CDCl3) δ ppm: 14.7 (CH3), 27.1,
27.6, 28.5, 30.0, 32.2, and 36.0 (Six CH2) and 116.7, 134.8, 140.3, 142.8,
144.1, 148.7, and 149.2 (thieno-pyrimidine-triazolo carbon atoms). MS
(m/z): 338 (M+) 100%.
4-(3,5-Dimethyl-1H-pyrazol-1-yl)-2-methylthio-
cyclohepteno[4,5]thi-eno[2,3-d]pyrimidine (24)
A mixture of compound 18 (2.80 g, 0.01 mole) and pentane-2,4-dione
(1.00 g, 0.01 mole) was heated under reflux in absolute ethanol (30 mL)
for 6 h. The reaction mixture was allowed to cool to r.t. The precipitated
solid was collected by filtration, dried, and recrystallized from ethanol
to produce 24 as colorless crystals. IR spectrum (KBr) cm−1: 2927 (CH
1
aliphatic). H NMR (CDCl3) δ ppm: 1.65 (m, 2H, CH2), 1.70 (m, 2H,
CH2), 1.80 (m, 2H, CH2), 2.15 (m, 2H, CH2), 2.25 (s, 3H, CH3), 2.40 (s,
3H, CH3), 2.55 (s, 3H, CH3), 2.90 (m, 2H, CH2) and 6.05 (s, 1H, CH
pyrazolo proton). MS (m/z): 344 (M+) 100%, 330 (M-Me) 69.34 %.
2-Methylthio-4-[1,1,1-trifluoropentane-2,4-dione-4-hydrazone-
cyclohepteno[4,5]-thieno[2,3-d]pyrimidine] (25)
A
mixture of compound 18 (2.80 g, 0.01 mole) and 1,1,1-
trifluoropentane-2,4-dione (1.54 g, 0.01 mole) was heated under reflux
in absolute ethanol (30 mL) for 6 h. The reaction mixture was allowed
to cool to r.t. The precipitated solid was collected by filtration, dried,
and recrystallized from ethanol to produce 25 as colorless crystals. IR
spectrum (KBr) cm−1: 3567 (OH), 3159 (NH) and 2996 (CH aliphatic).
1H NMR (CDCl3) δ ppm: 1.50–2.00 (m, 6H, 3CH2), 2.10 (s, 3H, CH3),
2.60 (s, 3H, CH3), 2.85 (m, 2H, CH2), 2.70–2.90 (m, 2H, CH2), 3.10–
3.45 (d-d, 2H, CH2), and 8.50 (s, 1H, NH, D2O exchangeable). 13C NMR
(CDCl3) δ ppm: 14.0, 15.2 (Two CH3); 26.6, 27.2, 29.6, 29.9, 32.2, and
48.4 (Six CH2) and 118.9, 121.5, 125.7, 133.3, 138.3, 151.9, 156.3, and
161.8 (thienopyrimidine carbon atoms); 168.9 (CO). MS (EI + Q1MS
LMR UP LR): 416 (M+) 100%, 398 (M-18) 37.19 %

The Synthesis of Some New Derivatives
55
4-(Arylmethylenehydrazone)-2-methylthio-
cyclohepteno[4,5]thieno[2,3-d]-pyrimidine 26a–c:
General Procedure
A mixture of compound 18 (2.80 g, 0.01 mole) and the appropriate aro-
matic aldehyde (0.01 mole), dioxane (30 mL), and a catalytic amount of
piperidine were heated under reflux for 6 h. The reaction mixture were
allowed to cool to r.t., and then it was poured into water. The formed
precipitate was filtered off, washed with water, dried, and recrystallized
from dioxane to produce 26a,b.
4-(Phenylmethylenehydrazone)-2-methylthio-
cyclohepteno[4,5]thieno[2,3-d]pyrimidine (26a)
Compound 26a was obtained from compound 18 (2.80 g, 0.01 mole) and
benzaldehyde (1.06 g, 0.01 mole). The product was recrystallized from
dioxane to produce 26a as yellow crystals. IR spectrum (KBr) cm−1
:
1
3328 (NH), 3140 (NH) and 2969 (CH aliphatic). H NMR (CDCl3) δ
ppm: 1.70 (m, 4H, 2CH2), 1.85 (m, 2H, CH2), 2.60 (s, 3H, CH3), 2.80
(m, 2H, CH2), 3.35 (m, 2H, CH2), 7.40 (m, 4H, aromatic protons + CH
ethylenic proton), 7.70 (m, 2H, aromatic protons) and 8.35 (brs, 1H, NH,
D2O exchangeable). MS (m/z): 368.00 (M+) 100%.
4-(4-Chlorophenylmethylenehydrazone)-2-methylthio-
cyclohepteno[4,5]thieno[2,3-d]pyrimidine (26b)
Compound 26b was obtained from compound 18 (2.80 g, 0.01 mole)
and 4-chlorobenzaldehyde (1.40 g, 0.01 mole). The product was recrys-
tallized from dioxane to produce 26b as yellow crystals. IR spectrum
1
(KBr) cm−1: 3345 (NH) and 2926 (CH aliphatic). H NMR (CDCl3) δ
ppm: 1.70 (m, 4H, 2CH2), 1.80 (m, 2H, CH2), 2.55 (s, 3H, CH3), 2.75 (m,
2H, CH2), 3.30 (m, 2H, CH2), 7.15 (s, 1H, CH), 7.40 (d, 2H, aromatic
protons), 7.70 (d, 2H, aromatic protons) and 8.35 (brs, 1H, NH, D2O
exchangeable). MS (m/z): 402 (M+) 100%.
4-(4-Methoxyphenylmethylenehydrazone)-2-
methylthiocyclohepteno[4,5]thieno-[2,3-d]pyrimidine (26c)
From compound 18 (2.80 g, 0.01 mole) and 4-methoxybenzaldehyde
(1.36 g, 0.01 mole). The product was recrystallized from dioxane to
produce 26c as yellow crystals. IR spectrum (KBr) cm−1: 3378 (NH)
and 2922 (CH aliphatic). 1H NMR (CDCl3) δ ppm: 1.70 (m, 4H, 2CH2),
1.85 (m, 2H, CH2), 2.60 (s, 3H, CH3), 2.75 (m, 2H, CH2), 3.30 (m, 2H,

56
A. S. Aly et al.
CH2), 3.85 (s, 3H, CH3), 6.90 (m, 3H, aromatic protons + CH ethylenic
proton), 7.70 (d, 2H, aromatic protons) and 10.20 (brs, 1H, NH, D2O
exchangeable). MS (m/z): 398 (M+) 100%.
CONCLUSION
This work deals with the synthesis of polynuclear thieno[2,3-
d]pyrimidine derivatives by intermolecular reactions of 2- or 4-
hydrazinothieno[2,3-d]pyrimidine with aliphatic acids, functional, and
bifunctional groups to give triazolo, pyrazolyl, and triazine derivatives.
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