Synthesis and reactions of some new heterocyclic compounds related to pyrrolylthieno[2,3-d]pyrimidines and thieno[2,3-d][4,5-d] dipyrimidines

Article abstract of DOI:10.1080/104265090509144

Condensation of ethyl-5-amino-2,4-diphenylthieno[2,3-d]pyrimidine-6- carboxylate (3a) with 2,5-dimethoxy tetrahydrofurane in acetic acid gives the corresponding 5-pyrrolyl derivative 4, which in turn could be easily reacted with hydrazine hydrate in ethan

Full text of DOI:10.1080/104265090509144

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Phosphorus, Sulfur, and Silicon
and the Related Elements
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Synthesis and Reactions
of Some New Heterocyclic
Compounds Related
to Pyrrolylthieno[2,3-
d]Pyrimidines and Thieno[2,3-
d][4,5-d] Dipyrimidines
Maisa I. Abdel Moneam a
a Chemistry Department, Faculty of Science , Assiut
University , Assiut, Egypt
Published online: 21 Dec 2010.
To cite this article: Maisa I. Abdel Moneam (2005) Synthesis and Reactions of Some
New Heterocyclic Compounds Related to Pyrrolylthieno[2,3-d]Pyrimidines and
Thieno[2,3-d][4,5-d] Dipyrimidines, Phosphorus, Sulfur, and Silicon and the Related
Elements, 180:2, 375-388, DOI: 10.1080/104265090509144
To link to this article: http://dx.doi.org/10.1080/104265090509144
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Phosphorus, Sulfur, and Silicon, 180:375–388, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090509144
Synthesis and Reactions of Some New Heterocyclic
Compounds Related to Pyrrolylthieno[2,3-d]Pyrimidines
and Thieno[2,3-d][4,5-d] Dipyrimidines
Maisa I. Abdel Moneam
Chemistry Department, Faculty of Science, Assiut University,
Assiut, Egypt
Condensation of ethyl-5-amino-2,4-diphenylthieno[2,3-d]pyrimidine-6-carboxylate
(3a) with 2,5-dimethoxy tetrahydrofurane in acetic acid gives the corresponding 5-
pyrrolyl derivative 4, which in turn could be easily reacted with hydrazine hydrate
in ethanol yielding the carbohydrazide derivative 5. Reaction of 5 with aromatic
aldehydes, acetylacetone, carbon disulfide or phenylisothiocyanate gave pyrrolyl
derivatives 6–9 respectively. On the other hand, condensation of 5-(1-pyrrolyl)-
6-acetyl-2,4-diphenylthieno[2,3-d]pyrimidine 11 with benzaldehyde afforded the
corresponding chalcone 12, which on treatment with hydrazine hydrate, phenyl
hydrazine, or thiourea gave the pyrazolinyl derivatives 13, 14 and pyrimidinyl
derivative 15, respectively. Furthermore, some new pyrimidothienopyrimidne 16,
17a–d, 19, 20
were obtained using 5-amino-carboxamide 3c as starting
a–c
material.
Keywords Thienopyrimidine–pyrrolylthienopyrimidine–pyrimidothienopyrimidine
INTRODUCTION
The structural diversity and biological significance of fused pyrimidines
have aroused much attention in the past few years owing to their wide
range of biological activity.1 Many potential drugs have been modeled on
them, particularly in cancer and virus research.2,3 Also, thienodipyrim-
idines show anaphylactic activity,4 while thieno[2,3-d]pyrimidine prove
to exhibit antituberculouses5 and herpes virus inhibitory,6 and can
be used in fertility regulation therapies.7 On the other hand many
pyrroles have been investigated in relation to their pharmacologi-
cal activities, and they prove to exhibit anti-inflammatory activities,8
antitumer9 and antibiotic activities against various microorganisms.10
Within this context and also as a part of our research program
Address correspondence to Maisa I. Abdel Moneam, Chemistry Department, Faculty of
Science, Assiut University, Assiut 71516, Egypt. E-mail: maisaabdelmonem@hotmail.com
375

376
M. I. A. Moneam
dealing with the syntheses of several thieno[2,3-d]pyrimidines.11,12 We
planned to investigate a new route for the synthesis of novel thieno[2,3-
d]pyrimidines, pyrrolylthieno[2,3-d]pyrimidines, and thieno[2,3-d][4,5-
d]dipyrimidines with potential biological activities.
DISCUSSION
The starting 5-Cyano-2,6-diphenylpyrimidine-4(3H)thione (1) was
readily obtained by a previously described procedure.13 Compound
1 was reacted with different α-halocompounds, ethyl chloroacetate,
chloroacetone, chloroacetamide, phenacyl bromide, and chloroac-
etanilide in refluxing ethanol containing sodium acetate, to give the
expected 5-alkyl derivatives 2a–e in excellent yield. The latter com-
pounds 2a–e were cyclized to the required compounds 3a–e by heating
in ethanol containing sodium ethoxide.
Compound 3a was condensed with 2,5-dimethoxytetrahydorofurane
in acetic acid to give the corresponding 5-pyrrolyl derivative 4,14 which
could easily be reacted with hydrazine hydrate in ethanol affording the
carbohydrazide derivative 5. Condensation of 5 with aromatic aldehy-
des in refluxing ethanol afforded the hydrazone derivatives 6a–d. Sim-
ilarly, reaction of 5 with acetylacetone furnished the dimethylpyrazolyl
derivative 7.
SCHEME 1

New Pyrimidines and Thieno Dipyrimidines
377
SCHEME 2
Carbohydrazide 5 reacted with carbon disulfide in pyridine afforded
oxadiazolyl thione 8. Furthermore, when 5 was allowed to react with
phenylisothiocyanate in absolute ethanol, the product was identified
as Nꢀ-5-(1-pyrrolyl)-N4-phenyl-2,4-diphenylthieno[2,3-d]pyrimidin-6-
yl)carbonylthio-semicarbazide (9). Cyclization of thiosemicarbazide 9
into triazolyl derivative 10 was achieved in alcoholic sodium hydroxide
solution (Scheme 3).
Other new pyrrolylthieno[2,3-d]pyrimidines were obtained using 5-
amino-6-acetyl-2,4-diphemyl thieno[2,3-d]pyrimidine (3b) as starting
material. Thus, 3b was condensed with DMTHF in acetic acid to give
the corresponding pyrrolyl derivative 11 which was allowed to undergo
base-catalyzed Claisen–Schmidt reaction with benzaldehyde to give the
chalcone derivative 12, which was produced in good yield. The reactivity
of 12 as cholcone was tested via their cydocondensation reactions with
hydrazines and thiourea, affording pyrazolyl 13, 14 and pyrimidinyl 15
derivatives, respectively.
5-Amino-2,4-diphenylthieno[2,3-d]pyrimidine-6-carboxamide (3c)
also proved to be a versatile synthon for some newly fused thienopy-
rimidine moieties. Thus the reaction of 3c with carbon disulfide in
hot pyridine led to the formation of oxopyrimidothienopyrimidine 16,
which was easily S-alkylated with different halo compounds in ethanol

378
M. I. A. Moneam
SCHEME 3
SCHEME 4

New Pyrimidines and Thieno Dipyrimidines
379
SCHEME 5
containing a catalytic amount of sodium acetate to give the expected
S-alkylated products 17a–d in good yields. Compound 17c underwent
smooth cyclodehydration in concentrated sulfuric acid15 to furnish
thiazolopyrimido-thienopyrimidine 18 in moderate yield (Scheme 5).
Treatment of 16 with hydrazine hydrate in pyridine led to the forma-
tion of 2,4-diphenyl-6-hydrazinothieno[2,3-d][4,5-d]dipyrimidin-8(7H)-
one (19), which reacts easily with aromatic aldehydes in ethanol to
give the corresponding hydrazones 20a–c. Condensation of 19 with tri-
ethylorthoformate in ethanol in presence of a few drops of acetic acid
afforded the triazolo derivative 2116 (Scheme 6).
The structural formulae of all newly synthesized compounds were
elucidated and confirmed by elemental and spectroscopic analyses (cf.
Tables I, II).
EXPERIMENTAL
All melting points are uncorrected and measured on a Fisher–Johns
apparatus. IR spectra: Shimadzu IR-Spectrophotometer (KBr; νmax in
1
Cm−1); H-NMR spectra: Varian EM-390, 90 MHz spectrometer, TMS
as internal standard; MS: Jeol JMS-600; elemental analyses (C, H, N):

380
M. I. A. Moneam
SCHEME 6
Perkin. Elmer 240c elemental analyzer: sulpher and chlorine analysis:
oxygen flask method by the Micro Analytical Unite at Assiut University.
Reaction of 1 with Ethyl Chloroacetate, Chloroacetone,
Chloroacetamide, Phenacyl Bromide or Chloroacetanilide
Formation of Compounds 2a–e, General Procedure
A mixture of compound 1 (0.02 mol), sodium acetate (4.68 g, 0.03
mol) and the respective halo-compound (0.02 mol) in ethanol (100 ml)
was heated under reflux for 2 h. The precipitate that formed on cooling
was collected and recrystallized from ethanol to give 2a–e.
Cyclization of Compounds 2a–e; Formation of 3a–e;
General Procedure
Compounds 2a–e (0.01 mol) in sodium ethoxide solution (50 mg Na
in 25 ml absolute ethanol) was heated under reflux for 15 min. The solid
that formed while hot was collected and recrystallized from ethanol to
give yellow crystals 3a–e.
Ethyl 2,4-Diphenyl-5-(1-pyrrolyl)thieno[2,3-d]pyrimidine-
6-carboxylate (4)
A mixture of 3a (3.75 g; 0.01 mol) and 2, 5-dimethoxytetrahydro-
furane (0.01 mol) was refluxed in acetic acid (20 ml) for 3 h and then
allowed to cool. The solvent was removed under reduced pressure and
the residue was triturated several times with ethanol. The solid product
was filtered off and recrystallized from acetic acid as pale yellow crystals
of 4.

New Pyrimidines and Thieno Dipyrimidines
381
TABLE I Melting Points, Yield and Analytical Data (Cale/Found) of
the Prepared Compounds
M.P.
[◦C]
Yield
[%]
Mol. formula
(mol. wt)
Comp.
C
H
N
S
2a
155–157
160–161
173–175
178–180
244–245
184–185
229–230
259–260
209–210
194–195
178–180
229–230
288–290
298–300
278–280
308–310
145–147
188–200
248–250
259–260
173–175
164–165
89
91
88
85
87
85
81
83
85
85
79
76
71
73
71
75
73
72
77
65
79
87
C21H17N3O2S
(375.43)
67.18
67.35
69.56
69.71
65.90
65.77
73.71
73.56
71.09
71.17
67.18
67.33
69.56
69.17
65.90
66.04
73.71
73.54
71.09
71.26
70.59
70.32
67.15
67.54
72.13
72.48
70.30
70.09
67.48
67.94
70.84
70.33
70.71
70.32
63.57
63.09
65.90
65.64
68.17
68.43
72.89
72.62
76.99
77.21
4.48
4.41
4.34
4.11
4.07
4.31
4.17
4.03
4.26
4.32
4.48
4.06
4.34
4.03
4.07
4.51
4.17
4.22
4.26
4.41
4.47
4.77
4.13
4.47
4.23
4.42
4.37
4.50
3.77
3.31
4.83
4.50
4.42
4.47
3.31
3.11
4.05
4.30
3.81
3.25
4.32
4.08
4.37
4.29
11.19
11.27
12.17
12.52
16.18
16.35
10.31
10.55
13.27
13.52
11.19
11.52
12.17
12.52
16.18
16.39
10.31
10.82
13.27
13.18
9.87
8.54
8.73
9.27
9.36
9.24
9.09
7.86
7.34
7.58
7.74
8.54
8.72
9.27
8.87
9.24
9.58
7.86
7.71
7.58
7.98
7.52
7.83
7.78
7.57
6.41
6.12
6.05
6.21
6.00
5.82
5.91
6.07
6.73
6.61
14.12
13.97
11.72
11.44
12.13
12.32
8.10
8.37
6.63
6.94
2b
2c
2d
2e
3a
3b
3c
3d
3e
4
C20H15N3OS
((345.41)
C19H14N4OS
(346.29)
C25H17N3OS
(407.48)
C
C
C
C
C
C
25H18N4OS
(422.35)
21H17N3O2S
(375.43)
20H15N3OS
(345.41)
19H14N4OS
(346.29)
25H17N3OS
(407.48)
25H18N4OS
(422.35)
C25H19N3O2S
(425.34)
9.90
5
C
C
C
C
23H17N5OS
(411.34)
30H21N5OS
(499.51)
31H23N5O2S
(529.60)
17.02
16.94
14.02
13.90
13.22
13.49
13.11
13.05
15.49
15.39
14.73
14.06
15.44
15.15
15.37
15.05
15.90
16.07
10.62
10.34
8.68
6a
6b
6c
6d
7
30H20N5OSCl
(533.96)
C32H26N6OS
(542.51)
C28H21N5OS
(475.56)
8
C24H15N5OS2
(453.41)
9
C30H22N6OS2
(546.73)
10
11
12
C
30H20N6S2
(528.50)
C24H17N3OS
(395.47)
C31H21N3OS
(483.58)
8.26
(Continued on next page)

382
M. I. A. Moneam
TABLE I Melting Points, Yield and Analytical Data (Cale/Found) of
the Prepared Compounds (Continued)
M.P.
[◦C]
Yield
[%]
Mol. formula
(mol. wt)
Comp.
C
H
N
S
13
193–195
223–225
183–185
308–310
258–260
280–282
263–265
>300
71
73
75
84
87
85
87
81
63
79
73
73
71
69
C31H23N5S
(497.61)
74.82
74.57
77.46
77.62
70.97
70.49
61.85
61.64
62.16
62.46
60.74
61.27
66.38
65.62
64.47
64.37
68.29
68.14
62.18
61.94
68.36
68.09
66.67
66.70
63.71
63.88
63.65
63.41
4.65
4.81
4.70
4.21
4.27
4.62
3.08
3.46
3.65
3.13
3.82
3.96
3.58
3.85
3.67
3.41
4.06
4.21
3.62
3.31
3.79
3.46
3.96
3.34
3.34
3.13
3.02
3.52
14.07
14.33
12.20
12.65
12.93
12.50
14.42
14.61
12.60
12.06
11.80
11.07
11.05
11.07
13.42
13.37
11.37
11.62
21.75
21.52
17.71
17.63
16.66
16.17
16.51
16.94
21.20
20.93
6.44
6.09
5.58
14
C37H27N5S
(573.71)
5.37
15
C32H23N5S2
(541.51)
11.84
11.60
16.51
16.45
13.99
14.43
13.51
13.30
12.65
13.13
12.29
12.06
13.02
12.97
8.30
8.11
6.75
6.46
6.35
6.09
6.29
6.18
8.07
16
C20H12N4OS2
(388.36)
C23H16N4O2S2
(444.40)
C24H18N4O3S2
(474.52)
17a
17b
17c
17d
18
C28H18N4O2S2
(506.58)
C28H19N5O2S2
(521.59)
298–300
283–285
>360
C28H20N4OS2
(492.45)
19
C20H14N6OS
(386.31)
20a
20b
20c
21
C27H18N6OS
(474.39)
>360
C
C
C
28H20N6O2S
(504.39)
27H17N6OSCl
(508.5)
21H12N6OS
(396.26)
>300
>300
7.89
2,4-Diphenyl-5-(1-pyrrolyl)thieno[2,3-d]pyrimidine-
6-carbohydrazide (5)
A mixture of 4 (4.25 g; 0.01 mol) and hydrazine hydrate (3 ml) in
ethanol (20 ml) was refluxed for 3 h. The sold product which formed
in hot mixture was filtered off and crystallized from dioxane as orange
crystals from 5.
Arylidine 2,4-Diphenyl-5-(1-pyrrolyl)thieno[2,3-d]pyrimidine-
6-carbohydrazone (6a–d)
A mixture of carbohydrazide 5 (4.11 g; 0.01 mol) and appropriate
aromatic aldehyde (0.01 mol) in ethanol (30 ml) was refluxed for 4 h,
then allowed to cool. The solid product was collected and crystallized
from ethanol into yellow–orange crystals from 6a–d.

New Pyrimidines and Thieno Dipyrimidines
383
TABLE II TR, 1HNMR and Mass Spectral Data
Compound
IR [Cm−1
]
1HNMR [ppm]
no.
2a
2900 ( CH aliphatic); 2200
(C N); 1710 (C O)
(DMSO-d6): 7.3–8.2 (m, 10H, Ar-H); 4.5 (s,
2H, SCH2); 3.7–3.9 (q, J = 7.0, 2H, CH2
ester); 1.2–1.3 (t, J = 7.0, 3H, CH3 ester)
(DMSO-d6): 7.2–8.2 (m, 10H, Ar-H); 3.9 (s,
2H, SCH2); 2.4 (s, 3H, CH3)
(DMSO-d6): 7.5–8.5 (m, 10H, Ar-H); 4.2 (s,
2H, SCH2); 5.6 (s, 2H, NH2)
(DMSO-d6): 7.2–8.5 (m, 15H, Ar-H); 5.1 (s,
2H, SCH2)
2b
2c
2d
2e
3a
2200 (C N); 1690 (C O)
3400–3300 (NH2); 2200
(C N); 1670 (C O)
2200 (C N); 1670 (C O)
3200 (NH); 2200 (C N);
1670 (C O).
3400, 3310 (NH2); 2900
(DMSO-d6): 11.0 (s, 1H, NH); 7.5–8.7 (m,
15H, Ar-H); 4.3 (s, 2H, SCH2)
(DMSo-d6): 7.3–8.1 (m, 10H, Ar-H); 5.5 (s,
2H, NH2); 3.3–3.5 (q, J = 7.0, 2H, CH2
ester); 1.3–1.5 (t, J = 7.0, 3H, CH3 ester)
(DMSo-d6): 7.5–8.8 (m, 10H, Ar-H) 5.9 (s,
2H, NH2); 2.5 (s, 3H, CH3)
(
CH aliphatic); 1710
(C O)
3480–3300 (NH2); 1690
(C O)
3400–3300 (NH2); 1670
(C O)
3450–3300 (NH2); 1690
(C O)
3100, 3450, 3300 (NH, NH2)
1670(C O)
2950 ( CH aliphatic); 1715
(C O)
3b
3c
3d
3e
4
—
(DMSo-d6): 7.3–8.5 (m, 15H, Ar-H); 5.5 (s,
2H, NH2)
(DMSo-d6): 10.7 (s, 1H, NH); 7.5–8.9 (m,
15H, Ar-H); 5.8 (s, 2H, NH2)
(CDCl3): 7.5–8.6 (m, 10H, Ar-H) 6.3–6.5
(m, 2H, 2CH pyrryl); 5.7–5.9 (m, 2H,
2CH pyrryl); 4.2 (q, J = 7.0, 2H, CH2
ester); 1.3–1.5 (t, J = 7.0, 3H, CH3 ester)
5
3310, 3300, 3230 ( NHNH2) (DMSO-d6): 9.5 (s, 1H, NH); 7.5–8.6 (m,
1650 (C O)
10H, Ar-H); 6.1–6.3 (m, 2H, 2CH
pyrryl); 5.6–5.8 (m, 2H, 2CH pyrryl);
5.5(s, 2H (NH2)
6a
6b
3180 (NH); 1650 (C O)
(DMSO-d6): 9.3 (s, 1H, NH); 7.3–8.9 (m,
16H, Ar-H + N CH); 5.7–5.9 (m, 2H,
2CH pyrryl); 6.2–6.5 (m, 2H, 2CH
pyrryl)
3170 (NH); 1645 (C O)
(DMSO-d6): 9.5 (s, 1H, NH); 7.5–8.8 (m,
16H, Ar-H +
N CH); 5.8–6 (m, 2H,
2CH pyrryl); 6.2–6.3 (m, 2H, 2CH
pyrryl); 3.5 (s, 3H, OCH3)
6c
6d
7
3170 (NH); 1650 (C O)
3170 (NH); 1650 (C O)
1650 (C O); 1590 (C N)
—
—
(DMSO-d6): 7.2–8.3 (m, 10H, Ar-H);
6.2–6.4 (m, 2H, 2 CH pyrryl); 6.1 (s,
1H1 CH pyrazole); 5.9–6.0 (m, 2H,
2-CH pyrryl); 2.4, 2.2 (2s, 6H, 2CH3)
(Continued on next page)

384
M. I. A. Moneam
TABLE II TR, 1HNMR and Mass Spectral Data (Continued)
Compound
IR [Cm−1
]
1HNMR [ppm]
no.
8
9
3210 (NH); 1610 (C N)
(DMSO-d6): 10.1 (s, 1H, NH); 7.7–8.5
(m, 10H, Ar-H); 5.9–6.1 (m, 2H, 2CH
pyrryl); 6.2–6.5 (m, 2H, 2CH pyrryl)
(DMSO-d6): 9.5(s, 2H, 2NH); 10.3 (s, 1H,
NH); 7.3–8.6 (m, 15H, Ar-H); 5.9–6.1
(m, 2H, 2CH pyrryl); 6.2–6.4 (m, 2H,
2CH pyrryl)
3310, 3200, 3150 (3NH) 1640
(C O); 1590 (C N)
10∗
11
3210 (NH); 1600 (C N)
1660 (C O)
(DMSO-d6): 9.5 (s, 1H, NH); 7.8–8.9 (m,
15H, Ar-H); 6.2–6.4 (m, 2H, 2CH
pyrryl); 5.6–5.8 (m, 2H, 2CH pyrryl).
(DMSO-d6): 7.7–8.9 (m, 10H, Ar-H);
6.1–6.3 (m, 2H1 2CH pyrryl); 5.8–5.6
(m, 2H, 2CH pyrryl); 2.7 (s, 3H,
COCH3)
12∗
13
1660 (C O) and 1590 (C N)
3200 (NH) and 1590 (C N)
(DMSO-d6): 7.9–8.2 (m, 17H, Ar-H and
-
CH CH-); 6.2–6.1 (m, 2H, 2CH
pyrryl); 6.5–6.3 (m, 2H, 2CH pyrryl)
(DMSO-d6): 12.1 (s, 1H, NH); 7.7–8.6
(m, 15H, Ar-H); 5.9–6.1 (m, 2H, 2CH
pyrryl); 6.4–6.2 (m, 2H, 2CH pyrryl);
4.6–4.8 (t, 1H, CH pyrazoline);
3.3–3.5 (m, 2H1 CH2 pyrazoline)
—
(DMSO-d6): 9.7, 10.5 (2s, 2H, 2NH);
7.5–8.8 (m, 17H, 15Ar-H and 2CH
pyrimidine); 6.1–6.3 (m, 2H, 2CH
pyrryl); 6.5–6.6 (m, 2H, 2CH pyrryl)
(T.FA): 7.5-8.7 (m, 10H, Ar-H)
14∗
1600(C N)
3320, 3100 (2NH); 1590
(C N) and 1230 (C S)
15∗∗
16
3400, 3100 (2NH) and 1660
(C O)
17a
3200 (NH); 1680, 1640
(2C O) and 1610 (C N)
(DMSO-d6): 10.3 (s, 1H, NH); 7.3–8.6
(m, 10H, Ar-H); 4.5 (s, 2H, SCH2); 2.9
(s, 3H, CH3)
17b
3290 (NH); 2900 ( CH
aliphatic); 1710, 1660
(2C O) and 1600 (C N)
3200 (NH); 1680 (C O) and
1600 (C N)
(DMSO-d6): 10.1 (s, 1H, NH); 7.2–8.5 (m,
10H, Ar-H); 4.5 (s, 2H, SCH2); 3.9 (q,
2H, CH2 ester); 1.5 (t, 3H, CH3 ester)
—
17c
17d
3220, 3100 (2NH); 1670
(C O) and 1590 (C N)
(DMSO-d6): 9.5, 10.3 (2s, 2H, 2NH);
7.3–8.6 (m, 15H, Ar-H); 4.6 (s, 2H,
SCH2)
(TFA): 8.2 (s, 1H, thiazole-CH); 7.1–8
(m, 10H, Ar-H)
(DMSO-d6): 9.5, 10.3 (2s, 2H, 2NH);
7.6–8.7 (m, 10H, Ar-H); 4.7 (br, 2H,
NH2)
18∗∗
19
1690 (C O) and 1600 (C N)
3380, 3280, 3200 (NHNH2,
NH); 1670 (C O) and 1600
(C N)
(Continued on next page)

New Pyrimidines and Thieno Dipyrimidines
385
TABLE II TR, 1HNMR and Mass Spectral Data (Continued)
Compound
IR [Cm−1
]
1HNMR [ppm]
no.
20a
20b
3310, 3200 (2NH); 1670
(C O) and 1610 (C N)
3320, 3200 (2NH); 1675
(C O) and 1600 (C N)
(DMSO-d6): 9.3, 10.1 (2s, 2H, 2NH);
7.2–8.6 (m, 16H, Ar-H and N CH)
(DMSO-d6): 9.5, 10.1 (2s, 2H, 2NH)
7.5–8.7 (m, 15H, Ar-H and
2.7 CS, 3H, OCH3)
N CH-);
20c
21∗
3310, 3200 (2NH) 1670
(C O) and 1590 (C N)
3400 (NH); 1670 (C O) and
1590 (C N).
—
(DMSO-d6): 10.5 (s, 1H, NH); 8.6 (s, 1H,
triazol CH); 7.2–8.5 (m, 10H, Ar-H)
aMS of 10: m/z (fragment, %): 529 (M+, 80); 463 (M+-C4H4N, 90).
bMS of 12: m/z (fragment, %): 484 (M+, 56); 407 (M+-C6H5, 100).
cMS of 14: m/z (fragment, %): 574 (M+, 60); 497 (M+-C6H5, 90).
dMS of 15: m/z (fragment, %): 542 (M+, 45); 476 (M+-C4H4N, 85).
eMS of 21: m/z (fragment, %): 396 (M+, 25); 395 (M+−1, 70); 394 (M+−2, 73).
f C13-NMR spectra of compounds 15, 18 were recorded on a Jeol LA 400
MHzFT-NMR.
gC13-NMR of 15: 164, 166, 128, 130 (pyrimidine); 127, 137 (thiophene); 118, 110
(pyrryl); 103, 59, 149, 179 (thioxopyrimidine); 126–142 (Aromatic).
hC13-NMR of 18: 163, 165, 127, 136 (pyrimidine); 144, 136 (thiophene) 163, 165
(pyimidinone); 86, 145 (thiazole); 127–136 (aromatic).
6-[3ꢀ,5ꢀ-Dimethyl-pyrazoleylcarbonyl]- 2,4-Diphenyl-5-
(1-pyrrolyl)thieno[2,3-d]pyrimidine (7)
A mixture of 5 (4.11 g; 0.01 mol) and acetylacetone (1 g; 0.01 mol)
in ethanol in the presence of a few drops from AcOH was refluxed for
6 h. The solid product which separated was collected by filtration and
recrystallized from acetic acid to give yellow crystals of 7.
2,4-Diphenyl-5-(1-pyrrolyl)-6-(5ꢀ-thioxo-1,3,4-oxadiazol-2-yl)-
thieno[2,3-d]pyrimidine 8
A mixture of compound 5 (4.11 g; 0.01 mol) and carbon disul-
fide (5 ml) in pyridine (20 ml) was heated on a water bath for 12
h. The solid product which separated from the hot mixture was col-
lected by filtration and recrystallized from dioxane as orange crystals
from 8.
2,4-Diphenyl-6-(oxophenylthiosemicarbazide)-5-(1-pyrrolyl)-
thieno[2,3-d]pyrimidine (9)
A mixture of 5 (4.11 g; 0.01 mol) and phenylisothiocyanate (1.35 g;
0.01 mol) in ethanol was refluxed for 4 h. Pale yellow crystalline product

386
M. I. A. Moneam
obtained on heating was collected by filtration and recrystallized from
dioxane.
2,4-Diphenyl-6-(1,5-dihydro-4-phenyl-5-thioxo-s-triazol-3-yl)-
5-(1-pyrrolyl)thieno [2,3-d]pyrimidine (10)
Thiosemicarbazide 9 (5.46 g; 0.01 mol) was dissolved in 2N alcoholic
sodium hydroxide (20 ml) and heated for 3 h. the solution was cooled
and acidified with dilute. HCl, the separated product, was collected by
filtration and crystallized from dioxane as yellow crystals from 10.
2,4-Diphenyl-6-methylcarbonyl-5-(1-Pyrrolyl)thieno[2,3-d]-
pyrimidine (11)
This compound was synthesized following an analogous procedure
that for compound 4. Compound 11 was separated from dioxane as
deep yellow crystals.
1 (2,4-Diphenyl-5-(1-pyrrolyl)thieno[2,3-d]pyrimidine-6-yl)-
3-phenyl-2-propen-1-one (12)
To a solution of 11 (3.95 g; 0.0l mol) in hot ethanol (100 ml) containing
sodium hydroxide (2 g, 0.05 mol), the benzaldehyde (1.06 g; 0.01 mol)
was added. The resulting mixture was stirred at 50–55 for 4 h and then
left to cool. The separated solid was collected and recrystallized from
dioxane to give orange crystals of 12.
2,4-Diphenyl-6-(5-phenyl-∆2-pyrazolin-3-yl)-5-(1-pyrrolyl)-
thieno[2,3-d]pyrimidine (13)
A mixture of 12 (0.96 g; 0.002 mol) and hydrazine hydrate (3 ml) in
ethanol (30 ml) was heated under reflux for 4 h. The separated solid
product was collected and recrystallized from ethanol-CHCl3 mixture
to give yellow crystals of 13.
2,4-Diphenyl-6-(1,5-diphenylpyrazolin-3-yl)-5-(1-pyrrolyl)-
thieno[2,3-d]pyrimidine (14)
A mixture of 12 (4.83 g; 0.01 mol) and phenyl hydrazine (1.08 g;
0.01 mol) in ethanol (30 ml) was heated under reflux. The solid product
which separated during heating was collected and recrystallized from
ethanol-CHCl3 mixture as orange crystals from 14.
2,4-Diphenyl-6-(2,3-dihydro-2-thioxo-1,3-pyrimidin-6-yl)-5-
(1-pyrrolyl)thieno[2,3-d]pyramidine (15)
A mixture of 12 (4.83 g; 0.01 mol) and thiourea (0.76 g; 0.01 mol) in
ethanol (30 ml) and a few drops of piperidine were added. The reaction
mixture was heated under reflux for 4 h. The precipitate that formed

New Pyrimidines and Thieno Dipyrimidines
387
while hot was collected by filtration and recrystallized from dioxane as
deep yellow crystals of 15.
2,4-Diphenyl-5,6-dihydro-6-thioxothieno[2,3-d][4,5-d]-
dipyrimidin-8(7H)one (16)
A mixture of compound 3C (3.46 g; 0.01 mol) and carbon disulfide
(5 ml) in pyridine (20 ml) was heated on a water bath for 12 h. The solid
product which separated from hot mixture was collected by filtration
and crystallized from dioxane as orange needles from 16.
Reactions of 16 with Chloroacetone, Ethyl Chloroactate,
Phenacylbromide, and Chloroacetanilide
Formation of Compounds 17a−d; General Procedure
A mixture of compound 16 (3.88 g; 0.01 mol), sodium acetate (1.46 g;
0.02 mol), and respective halo compounds (0.01 mol) was heated under
reflux for 1–2 h. The precipitate that formed on cooling was collected
by filtration, washed with water, and crystallized from ethanol-CHCl3
mixture as pale yellow crystals of 17a–d.
2,4,8-Triphenylthiazole[3ꢀꢀ,2ꢀꢀ:1ꢀ,2ꢀ]pyrimido[4ꢀ,5ꢀ:4,5]thieno-
[2,3-d]pyrimidin-9-one (18)
To a solution of 17c (1.0 g; 0.002 mol) in glacial acetic acid (15 ml),
concentrated H2SO4 (10 ml) was added and the mixture was gently
heated for 8 h. After cooling reaction mixture was poured into ice water
and neutralized with 5% aqueous sodium bicarbonate. The precipitated
was filtered off, washed well with water, and crystallized from dioxane
as yellow crystals of 18.
2,4-Diphenyl-6-hydrazinothieno[2,3-d][4,5-d]dipyrimidin-8(7H)
one (19)
A mixture of compound 16 (0.77 g; 0.002 mol) and 99% hydrazine
hydrate (2 ml) in pyridine (10 ml) was heated under reflux for 10 h until
H2S gas ceased, then allowed to cool. The solid product was collected,
washed well with ethanol, and recrystallized from pyridine as orange
crystals of 19.
6-Arylidenehydrazion-2,4-diphenyl-5,6-dihydrothieno[2,3-d]-
[4,5-d]dipyrimi-din-8 (7H) one (20a–c)
A mixture of 19 (3.86 g; 0.01 mol) and the respective aldehyde
(0.01 mol) in ethanol (25 ml) was refluxed for 3 h. The solid product
that precipitated by cooling was collected and recrystallized from diox-
ane as orange crystals of 20a–c.

388
M. I. A. Moneam
2,4-Diphenyl-6(H)-s-triazolo[3ꢀꢀ,4ꢀꢀ:1ꢀ,2ꢀ]pyrimido[4ꢀ,5ꢀ:4,5]-
thieno[2,3-d]pyrimidine (21)
A mixture of hydrazion derivative 19 (3.86 g; 0.01 mol) and triethy-
lorthoformate (0.12 mol) in ethanol in presence of few drops of acetic
acid, was refluxed for 3 h. The solid product which separated from the
hot mixture was filtered off and recrystallized from acetic acid as yellow
crystals of 21.
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