Synthesis of some new fused azines of expected bio-responses

Article abstract of DOI:10.1080/10426500490262306

4-Anisy1-5,6-polymethylene-3-cyanopyridine-2(1H)-thiones 1 were reacted with chloroacetonitrile in alcoholic KOH to give theino[2,3- b]pyridine derivatives 2. Enaminonitriles 2 were reacted with each of HCOOH, formamide / HCOOH / DMF mixture and cyanamide / HCl to give 3, 4, and 5, respectively, whereas boiling 2 in a proper solvent and basic catalyst with each of CS ₂ and thiourea yielded 6 and 7 respcetively. On the other hand, fused pyridine derivatives 8, 9, and 10 were obtained by re fluxing 2 with each of malononitrile, ethyl cyanoacetate, and benzalmalononitrile in alcoholic triethylamine mixture. Also, fused pyrazoles and benzo-1,4-diazepines 12 and 14 were synthesized.

Full text of DOI:10.1080/10426500490262306

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Phosphorus, Sulfur, and Silicon and the Related
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SYNTHESIS OF SOME NEW FUSED AZINES OF EXPECTED
BIO-RESPONSES
Mohie A. F. Sharaf a , Sherif M. Sherif a & Nasser A. A. Ibraheim b
a Cairo University , Giza, Egypt
b Agriculture Research Center, Dokki , Giza, Egypt
Published online: 11 Aug 2010.
To cite this article: Mohie A. F. Sharaf , Sherif M. Sherif & Nasser A. A. Ibraheim (2004) SYNTHESIS OF SOME NEW FUSED
AZINES OF EXPECTED BIO-RESPONSES, Phosphorus, Sulfur, and Silicon and the Related Elements, 179:2, 293-303, DOI:
10.1080/10426500490262306
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Phosphorus, Sulfur, and Silicon, 179:293–303, 2004
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Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490262306
SYNTHESIS OF SOME NEW FUSED AZINES
OF EXPECTED BIO-RESPONSES
Mohie A. F. Sharaf,a Sherif M. Sherif,a
and Nasser A. A. Ibraheimb
Cairo University, Giza, Egypt;a and Agriculture Research
Center, Dokki, Giza, Egyptb
(Received March 31, 2003; accepted August 4, 2003)
4-Anisy1–5,6-polymethylene-3-cyanopyridine-2(1H)-thiones 1 were re-
acted with chloroacetonitrile in alcoholic KOH to give theino[2,3-
b]pyridine derivatives 2. Enaminonitriles 2 were reacted with each of
HCOOH, formamide/HCOOH/DMF mixture and cyanamide/HCl to
give 3, 4, and 5, respectively, whereas boiling 2 in a proper solvent and
basic catalyst with each of CS2 and thiourea yielded 6 and 7 respce-
tively. On the other hand, fused pyridine derivatives 8, 9, and 10 were
obtained by refluxing 2 with each of malononitrile, ethy1 cyanoacetate,
and benzalmalononitrile in alcoholic triethylamine mixture. Also, fused
pyrazoles and benzo-1,4-diazepines 12 and 14 were synthesized.
Keywords: B-enaminonitriles; pyridothienopyridines; pyridothienopy-
rimdines; thienobenzodiazepines; thienopyridines
Thieno[2,3-b]pyridine derivatives have been of recent interest because
of their broad spectrum of biological activities. Such a ring system is re-
ported to have bactericidal activities,1 antiviral activities,2 antianaphy-
lactics, antiinflammatories, and antihypertensive properties.3 It is also
useful as an allergy inhibitor,4 cardiovascular agent,5−7 antiAIDS,8,9
potential drug, and chemical and pharmaceutical intermediate.10
Prompted by the aforesaid biological and medicinal activities and in
connection with our synthetic program11,12 aimed at the synthesis of
several polyfunctionally substituted thieno[2,3-b]pyridine, thieno[3,2-
d]pyrimidine derivatives and other heteroannulated ring systems
related to thieno[2,3-b]pyridine of expected biological activity, sam-
ples of differently substituted thieno[2,3-b]pyridine and thieno[3,2-
d]pyrimidine derivatives were synthesized.
Address correspondence to M. A. F. Sharaf, Department of Chemistry, Faculty of Sci-
ence, University of Cairo, Giza, A. R. Egypt. E-mail: mafsharaf@hotmail.com
293

294
M. A. F. Sharaf et al.
RESULTS AND DISCUSSION
The reaction of the recently prepared 4-anisyl-5,6-polymethylene-
3-cyanopyridine-2-(1H)thiones 1a,b13 with chloroacetonitrile in al-
coholic KOH seems to be a facile convenient route for synthe-
sis of 3-amino-4-(p-anisyl)-5,6-polymethylenethieno[2,3-b]pyridine-2-
carbonitriles 2a,b. This reaction proceeds as the reported ones of
haloesters, haloketones, and haloamides with pyridine-2(1H)thiones.14
Both elemental and spectral data of 2a,b were inconsistent with the
assigned structure (cf. Experimental).
Compounds 2a,b as a typical enaminonitriles can be used as
a strategic starting material for the synthesis of different fused
hetercycles. Thus, compounds 2a,b reacted with formic acid on
heating several hours, to yield 9-(p-anisyl)-3,4-dihydro-4-oxo-7,8-
polymethylenepyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-d]pyrimidines 3a,b.
Refluxing each of the compounds 2a,b in formamide/formic
acid/DMF mixture for 10 h gave the expected single product
which can be formulated as 4-amino-9-(p-anisyl)-7,8-polymethylene-
pyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-d]pyrimidines 4a,b. These reactions were
shown in our previous work on 3-aminothiazolo[3,2-a]pyrimidine-
2-carbonitrile derivatives.15,16 Also, compounds 2a,b reacted with
cyanamide/HCl in dioxane by heating under reflux for 24 h to give 9-
( p-anisyl )-2,4-diamino-7,8-polymethylenepyrido[ 3ꢁ,2ꢁ:4,5 ]thieno-[ 3,2-
d]pyrimidines 5a,b. In addition, refluxing of 2a,b with carbon
disulphide in dry pyridine gave 9-(p-anisyl)-2,4-disulphanyl-7,8-
polymethylenepyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-d]pyrimidines 6a,b. On the
other hand, treatment of 2a,b with thiourea in dioxane and tri-
ethylamine as a basic catalyst yielded the expected single product
that can be formulated as 4-amino-9-(p-anisyl)-2-sulphanyl-7,8-
polymethylenepyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-d]pyrimidine 7a,b. Com-
parison of the IR spectra of 2a,b, which contains a characteristic
absorption bands for stretching vibration of the conjugated nitrile
group in the 2200 cm−1 region with that of structures 3–7, reveals the
disappearance of this CN absorption band.

New Fused Azines
295
When solutions of 2a,b in ethanol containing triethylamine were
heated under reflux for 24 h with malononitrile, the corresponding
9-(p-anisyl)-2,4-diamino-7,8-polymethylenepyrido[3ꢁ,2ꢁ:4,5]thieno[ 3,2-
b]-pyridine-3-carbonitrile 8a,b were formed. Similary, the reaction of
2a,b with ethyl cyanoacetate gave 4-amino-9-(p-anisyl)-1,2-dihydro-2-
oxo-7,8-polymethylenepyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-b]pyridine-3-carbon-
itriles 9a,b. Also, compounds 2a,b underwent Micheal-type addition
to α-cyanocinnamonitrile in refluxing pyridine followed by cyclization
to furnish finally the corresponding 4-amino-9-(p-anisyl)-2-phenyl-
7,8-polymethylenepyrido[3ꢁ,2ꢁ:4,5]thieno[3,2-b]pyridine-3-carbonitrile
10a,b. Assignment of structures 8–10 were confirmed on the basis of
their correct elemental analysis as well as compatible spectral data.
Furthermore, fused pyrazoles and benzo-1,4-diazepines 12 and 14
were synthesized using 2a,b and bifunctionally amino compounds.
Thus, compounds 2a,b reacted with hydrazine hydrate in boiling
absolute ethanol in presence of triethylamine as a basic catalyst,
to give the isolated intermediates 3-aminothieno[2,3-b]pyridine-3-
amidine derivatives 11a,b. Heating of the amidine derivatives 11a,b
under reflux for 5 h in dioxane in the presence of conc. HCl
afforded the corresponding 3-amino-8-(p-anisyl)-6,7-polymethylene-
1H-pyrazolo[3ꢁ,4ꢁ:4,5]thieno[2,3-b]pyridines 12a,b. Similarly, com-
pounds 2a,b reacted with o-phenylenediamine to afford the
isolated intermediates 3-aminothieno[2,3-b]pyridine-3-amidine deriva-
tives 13a,b, which upon heating under reflux in dioxane in presence of
conc. HCl for 5 h, yielded 6-amino-11-(p-anisyl)-12H-9,10-polymethyle-
nepyrido[3ꢁ,4ꢁ:4,5]thieno[2,3-b]benzo-1,4-diazepines 14a,b.
EXPERIMENTAL
All melting points are uncorrected and were determined on an elec-
tric melting point (Gallenkamp) apparatus. IR spectra were recorded
1
(KBr) on a Pye Unicam SP-1000 Spectrophotometer. H NMR spectra
1
were recorded on a Varian H-Gemini 200 MHz and/or Jeol JNM-EX
270 MHz Spectrometers and chemical shifts are expressed in δ (ppm)

296
M. A. F. Sharaf et al.
using TMS as internal reference. Mass spectra were recorded on a
GCMS-QP 1000 EX mass Spectrometer operating at 70 eV. Microan-
alytical data were obtained from the Microanalytical Center at Cairo
University.

New Fused Azines
297
3-Amino-4-(p-anisyl)-5,6-polymethylenethieno[2,3-
b]pyridine-2-carbonitriles 2a,b
Chloroacetonitrile (0.76 g, 0.01 mmol) was added to a solution of the
appropriate 3-cyanopyridine-2(1H)-thiones 1a,b (0.01 mmol) in ethanol
(50 ml) containing potassium hydroxide (1.1 g, 0.02 mmol, disolved in
5 ml water) and the reaction mixture was refluxed for 3 h. The reaction
mixture was cooled at room temperature and poured gradually with
stirring onto crused ice and neutralized with dilute HCl (pH = 7). The
formed solid product, in each cuse, was filtered off and crystallized from
the proper solvent.
(2a)- yield 82%, m.p. = 185◦C (EtOH), IR spectrum ν (cm−1): 3314,
3210 (NH2), 2939 (CH-aliphatic) and 2203 (CN). The 1H NMR spectrum
(CDCl3) δ (ppm) = 1.8–2.1 (m, 6H, 3 CH2 ), 3.9 (s, 3H, OCH3) and 7.1–
7.8 (m, 6H, aromatic protons +NH2). Found C 67.1, H 4.8, N 13.1 and
S 10.1. Calculated for C18H15N3OS (321.38), C 67.27, H 4.71, N 13.08
and S 9.98. MS: m/z = 321, 25.6%.
(2b)- yield 86%, m.p. = 197–200◦C (EtOH), IR spectrum ν (cm−1):
3317, 3210 (NH2), 2942 (CH-aliphatic) and 2209 (CN). Found C 67.9,
H 5.4, N 12.3 and S 9.5. Calculated for C19H17N3OS (335.41), C 68.03,
H 5.11, N 12.53 and S 9.56. MS: m/z= 336.15, 16.64%.
9-(p-Anisyl)-3,4-dihydro-4-oxo-7,8-polymethylenepyrido-
[3ꢀ ,2ꢀ :4,5]-thieno[3,2-d]pyrimidines 3a,b
Each of 2a,b (0.005 mmol) was heated under reflux in formic acid (30 ml,
85%) for 10 h. The reaction mixture was then left aside to cool at
room temperature and poured onto cold water. The solid product so
formed, in each case, was filtered off and crystallized from the proper
solvent.
(3a)- yield 67%, m.p. = 275◦C (dil. DMF), IR spectrum ν (cm−1): 3320,
3215 (NH and/or OH), 2941 (CH-aliphatic) and weak band at 1724 (CO).
1H NMR spectrum (acetone-d6) δ (ppm) = 2.0–2.28 (m, 6H, 3 CH2), 3.9
(s, 3H, OCH3), 4.34 (s, 1H, OH), 5.1 (s, 1H, pyrimidine H-2) and 7.13–
7.53 (m, 4H, aromatic protons). Found C 64.3, H 4.5, N 12.3 and S 9.1.
Calculated for C19H15N3O2S (349.39), C 65.31, H 4.33, N 12.03 and S
9.17. MS: m/z= 349.3, 16.4%.
(3b)- yield 65%, m.p. = 230◦C (dioxane), IR spectrum ν (cm−1): 3340,
3250 (NH and/or OH), 2941 (CH-aliphatic) and weak band at 1708 (CO).
Found C 65.7, H 4.8, N 11.2 and S 9.1. Calculated for C20H17N3O2S
(363.42), C 66.09, H 4.72, N 11.56 and S 8.82.

298
M. A. F. Sharaf et al.
4-Amino-9-(p-anisyl)-7,8-polymethylenepyrido[3ꢀ ,2ꢀ :4,5]-
thieno[3,2-d]pyrimidines 4a,b
Each of 2a,b (0.005 mmol) was heated under reflux in a ternary mixture
of formic acid (5 ml, 85%), formamide (5 ml), and dimethyl-formamide
(5 ml), for 10 h. The reaction mixture was then cooled at room temper-
ature, poured onto cold water whereby, the solid product so formed, in
each case, was filtered off, and crystallized from the proper solvent.
(4a)- yield 80%, m.p. = 287◦C (acetonitrile), IR spectrum ν (cm−1):
3450 (NH2), 2950 (CH-aliphatic). 1H NMR spectrum (DMSO-d6) δ
(ppm) = 2.04–2.51 (m, 6H, 3CH2), 3.36 (s, 2H, NH2, D2O exchangable),
3.87 (s, 3H, OCH3), 5.38 (s, 1H, pyrimidine H-2) and 7.16–7.54 (2d, 4H,
aromatic protons) Found C 65.1, H 4.6, N 16.2 and S 9.2. Calculated
for C19H16N4OS (348.40), C 65.50, H 4.63, N 16.08 and S 9.20. MS:
m/z= 348.1, 18.2%.
(4b)- yield 72%, m.p. = 258◦C (acetonitrile), IR spectrum ν (cm−1):
3450 (NH2), 2955 (CH-aliphatic). Found C 65.7, H 5.1, N 15.1 and S
9.0. Calculated for C20H18N4OS (362.43), C 66.27, H 5.0, N 15.46 and
S 8.85. MS: m/z= 362, 42.4%.
9-(p-Anisyl)-2,4-diamino-7,8-polymethylenepyrido-
[3ꢀ ,2ꢀ :4,5]thieno[3,2-d]pyrimidines 5a,b
Cyanamide (0.42 g, 0.01 mmol) was added to each solution of 2a,b
(0.01 mmol) in dioxane (50 ml) containing a few drops of conc. HCl,
and the reaction mixture was heated under reflux for 24 h. The reac-
tion mixture was then cooled at room temperature, poured onto cold
water whereby the formed solid produc, in each case, was filtered off
and crystallized from the proper solvent.
(5a)- yield 57%, m.p. = 200◦C (dil. DMF), IR spectrum ν (cm−1):
3600–3300 (NH2) and 2940 (CH-aliphatic). Found C 62.5, H 4.5, N 18.9
and S 8.6. Calculated for C19H17N5OS (363.43), C 62.78, H 4.72, N 19.27
and S 8.82. MS: m/z= 363.3, 22.4%.
(5b)- yield 63%, m.p. = 198–200◦C (dil. DMF), IR spectrum ν (cm−1):
3600–3400 (NH2) and 2950 (CH-aliphatic). 1H NMR spectrum (acetone-
d6) δ (ppm) = 2.02–2.68 (m, 8H, 4 CH2), 3.96 (s, 3H, OCH3), 7.16–7.46
(m, 4H, aromatic protons) and 8.03, 8.18 (d, 4H, 2NH2). Found C 63.4,
H 5.1, N 19.0 and S 8.8. Calculated for C20H19N5OS (377.46), C 63.63,
H 5.07, N 18.55 and S 8.49.
9-(p-Anisyl)-2,4-disulphanyl-7,8-polymethylenepyrido-
[3ꢀ ,2ꢀ :4,5]thieno[3,2-d]pyrimidines 6a,b
A mixture of each of 2a,b (0.01 mmol) and carbon disulphide
(0.03 mmol) in dry pyridine (50 ml) was boiled under reflux for 8 h. The

New Fused Azines
299
reaction mixture was cooled and then poured onto cold water contain-
ing few drops of conc. HCl for neutralization. The formed solid product,
in each case, was filtered off and crystallized from the proper solvent.
(6a)- yield 85%, m.p. = 297◦C (dioxane), IR spectrum ν (cm−1): 3450
(NH), 2930 (CH-aliphatic) and 1190 (C S). Found C 57.9, H 3.7, N 10.7
and S 24.1. Calculated for C19H15N3OS3 (397.52), C 57.4, H 3.8, N 10.57
and S 24.19.
(6b)- yield 80%, m.p. = 285◦C (dioxane), IR spectrum ν (cm−1): 3500
(NH), 2950 (CH-aliphatic) and 1190 (C S). 1H NMR spectrum (acetone-
d6) δ (ppm) = 2.0–2.5 (m, 8H, 4 CH2), 3.9 (s, 3H, OCH3), 7.12–7.32 (m,
4H, aromatic protons) and 8.51–8.68 (d, 2H, 2NH). Found C 58.2, H
4.3, N 10.2 and S 23.1. Calculated for C20H17N3OS3 (411.55), C 58.36,
H 4.16, N 10.21 and S 23.37.
4-Amino-9-(p-anisyl)-2-sulphanyl-7,8-polymethyle-
nepyrido[3ꢀ ,2ꢀ :4,5]thieno[3,2-d]pyrimidines 7a,b
Thiourea (0.75 g, 0.01 mmol) was added to a solution of each of 2a,b
(0.01 mmol) in dry dioxane (60 ml) containing triethylamine (0.01 mmol)
and the reaction mixture was heated under reflux for 10 h. The reaction
mixture was cooled at room temperature and poured onto crused ice
containing few drops of dil. HCl. The formed solid product, in each
case, was filtered off and crystallized from the proper solvent.
(7a)- yield 78%, m.p. = 218–220◦C (EtOH), IR spectrum ν (cm−1):
3443 (NH2), 2926 (CH-aliphatic) and 1177 (C S). The 1H NMR (CDCl3)
at δ (ppm) = 1.9–2.18 (m, 6H, 3CH2), 3.9 (s, 3H, OCH3), 7.0–7.5 (m, 4H,
aromatic protons), 8.7 (s, 2H, NH2) and 9.9 (s, 1H, NH). Found C 62.3,
H 4.2, N 15.1 and S 17.1. Calculated for C19H16N4OS2 (364.46), C 62.6,
H 4.43, N 15.37 and S 17.58. MS: m/z= 364.2, 18.4%.
(7b)- yield 75%, m.p. = 235◦C (EtOH), IR spectrum ν (cm−1): 3450,
3350 (NH2), 2960 (CH-aliphatic) and 1208 (C S). Found C 63.2, H 4.9,
N 14.7 and S 16.9. Calculated for C20H18N4OS2 (378.5), C 63.46, H 4.8,
N 14.8 and S 16.9.
9-(p-Anisyl)-2,4-diamino-7,8-polymethylenepyrido-
[3ꢀ 2ꢀ :4,5]thieno[3,2-b]pyridine-3-carboniriles 8a,b
Each of 2a,b (0.01 mmol) was added to a solution of malononitrile
(0.66 g, 0.01 mmol) in absolute ethanol (50 ml) containing a catalytic
amount of triethylamine (3 drops). The reaction mixture was heated
under reflux for 12 h, cooled at room temperature, poured onto cold
water and neutralized with few drops of dil. HCl. The formed solid
product, in each case, was filtered off and crystallized from the proper
solvent.

300
M. A. F. Sharaf et al.
(8a)- yield 68%, m.p. = 265◦C (acetonitrile), IR spectrum ν (cm−1):
1
3450, 3350 (NH2), 2960 (CH-aliphatic) and 2200 (CN). H NMR spec-
trum (DMSO-d6) δ (ppm) = 2.02–2.25 (m, 6H, 3 CH2), 3.9 (s, 3H, OCH3),
7.19–7.42 (m, 4H, aromatic protons), 9.61 (s, 2H, NH2) and 10.73 (s, 2H,
NH2). Found C 64.8, H 4.3, N 17.9 and S 8.4. Calculated for C21H17N5OS
(387.45), C 65.1, H 4.42, N 18.08 and S 8.28. MS: m/z= 387.2, 19.2%.
(8b)- yield 75%, m.p. = 238–240◦C (acetonitrile), IR spectrum ν
(cm−1): 3500, 3350 (NH2), 2950 (CH-aliphatic) and 2200 (CN). Found
C 65.5, H 4.8, N 17.3 and S 8.1. Calculated for C22H19N5OS (401.47),
C 65.81, H 4.77, N 17.45 and S 7.99.
4-Amino-9-(p-anisyl)-1,2-dihydro-2-oxo-
7,8-polymethylenepyrido[3ꢀ ,2ꢀ :4,5]thieno[3,2-b]pyridine-
3-carbonitriles 9a,b
Each of 2a,b (0.01 mmol) was added to a solution of ethyl cyanoacetate
(0.01 mmol) in absolute ethanol (50 ml) containing a catalytic amount
of triethylamine (3 drops) and the reaction mixture was heated under
reflux for 12 h. The reaction mixture was cooled at room temperature
poured onto cold water and neutralized with few drops of dil. HCl. The
formed solid product, in each case, was filtered off and crystallized from
the proper solvent.
(9a)- yield 80%, m.p. = 275◦C (dil. DMF), IR spectrum ν (cm−1): 3310,
3200 (NH2), 2950 (CH-aliphatic), 2210 (CN) and 1680 (C O). Found C
64.8, H 4.2, N 14.5 and S 8.3. Calculated for C21H16N4O2S (388.43),
C 64.93, H 4.15, N 14.43 and S 8.25. MS: m/z= 388.2, 16.4%.
(9b)- yield 80%, m.p. = 287–290◦C (dil. DMF), IR spectrum ν (cm−1):
3500, 3350 (NH2), 2970 (CH-aliphatic), 2220 (CN) and 1680 (C O). 1H
NMR spectrum (DMSO-d6) δ (ppm) = 2.03–2.62 (m, 8H, 4 CH2), 3.81 (s,
3H, OCH3), 5.62 (s, 2H, NH2), 7.1–7.4 (m, 4H, aromatic protons) and
9.18 (s, 1H, NH). Found C 65.6, H 4.5, N 13.8 and S 7.9. Calculated for
C22H18N4O2S (402.46), C 65.65, H 4.50, N 13.92 and S 7.97.
4-Amino-9-(p-anisyl)-2-phenyl-7,8-polymethylenepyrido-
[3ꢀ ,2ꢀ :4,5]thieno[3,2-b]pyridine-3-carbonitriles 10a,b
Benzalmalononitrile (1.55 g, 0.01 mmol) was added to a solution of each
of 2a,b (0.01 mmol) in dry pyridine (50 ml) and the reaction mixture was
heated under reflux for 8 h. After complete reflux and cooling at room
temperature, the reaction mixture was then poured onto crushed ice
and neutralized with dil. HCl, whereby the solid precipitate so formed,
in each case, was filtered off and crystallized from ethanol.

New Fused Azines
301
(10a)- yield 65%, m.p. = 247◦C, IR spectrum ν (cm−1): 3450, 3350
(NH2), 2950 (CH-aliphatic) and 2215 (CN). Found C 71.9, H 4.5, N 12.5
and S 7.4. Calculated for C27H20N4OS (448.52), C 72.3, H 4.5, N 12.5
and S 7.15. MS: m/z= 448.4, 21.2%.
(10b)- yield 63%, m.p. = 233◦C, IR spectrum ν (cm−1): 3450,
3350 cm−1 (NH2), 2960 cm−1 (CH-aliphatic) and 2200 cm−1 (CN). Found
C 72.5, H 4.8, N 12.0 and S 7.0. Calculated for C28H22N4OS (462.55),
C 72.7, H 4.79, N 12.14 and S 6.93. MS: m/z= 462.5, 30%.
3-Amino-4-(p-anisyl)-5,6-polymethylenethieno[2,3-
b]pyridine-3-(N-amino)amidines 11a,b
Hydrazine hydrate (0.01 mmol) was added to a solution of 2a,b
(0.01 mmol) in absolute ethanol (50 ml) containing a catalytic amount
of triethylamine (3 drops) and the reaction mixture was heated under
reflux for 5 h. The reaction mixture was cooled at room temperature,
poured into cold water and neutralized with few drops of dil. HCl. The
formed solid product in each case, was filtered off and crystallized from
ethanol.
(11a)- yield 70%, m.p. = 195◦C, IR spectrum ν (cm−1): 3500–3380
(NH2), 2950 and 2940 cm−1 (CH-aliphatic). Found C 61.2, H 5.2, N 19.5
and S 9.3. Calculated for C18H19N5OS (353.44), C 61.16, H 5.41, N 19.82
and S 9.09. MS: m/z= 353.2, 8.97%.
(11b)- yield 72%, m.p. = 206◦C, IR spectrum ν (cm−1): 3485–3370
(NH2), 2950 and 2936 cm−1 (CH-aliphatic). Found C 62.0, H 5.5, N 19.0
and S 8.6. Calculated for C19H21N5OS (367.47), C 62.10, H 5.75, N 19.06
and S 8.72%.
3-Amino-8-(p-anisyl)-6,7-polymethylene-1H-pyrazolo-
[3ꢀ ,4ꢀ :4,5]thieno[2,3-b]pyridines 12a,b
Solutions of each of 11a,b (0.01 mmol) in dioxane (50 ml) containing
conc. HCl (10 drops) was heated under reflux for 6 h. The reaction
mixture was then left aside to cool at room temperature and poured
onto cold water, whereby the formed solid product, in each case, was
filtered off and crystallized from the proper solvent.
(12a)- yield 40%, m.p. = 187◦C (EtOH), IR spectrum ν (cm−1): 3480,
1
3320 (NH, NH2) and 2950 (CH-aliphatic). H NMR spectrum (DMSO)
δ (ppm) = 2.3–2.6 (m, 6H, 3 CH2), 3.9 (s, 3H, OCH3), 5.3 (s, 2H, NH2,
D2O exchangable), 7.0–7.5 (2d, 4H, aromatic protons) and 8.4 (s, 1H,
NH, D2O exchangable). MS: m/z= 336.4, 16.64%. Found C 64.3, H 4.9,
N 16.5 and S 9.6. Calculated for C18H16N4OS (336.41), C 64.26, H 4.76,
N 16.65 and S 9.53.

302
M. A. F. Sharaf et al.
(12b)- yield 45%, m.p. = 200◦C (EtOH), IR spectrum ν (cm−1): 3450,
3350 (NH, NH2), 2980 (CH-aliphatic). Found C 65.40, H 5.2, N 16.1 and
S 9.2. Calculated for C19H18N4OS (350.43), C 65.12, H 5.18, N 15.99
and S 9.15.
3-Amino-4-(p-anisyl)-5,6-polymethylenethieno[2,3-b]-
pyridine-3-(o-aminophenyl)amidines 13a,b
o-Phenylenediamine (1.1 g, 0.01 mmol) was added to a solution of each of
2a,b (0.01 mmol) in dry dioxane (40 ml) containing a catalytic amount of
triethylamine (3 drops) and the reaction mixture was then heated under
reflux for 5 h. After complet reflux and cooling at room temperature,
the reaction mixture was poured into cold water and neutralized with
dil. HCl. The formed solid product, in each case, was filtered off and
crystallized from ethanol.
(13a)- yield 65%, m.p. = 218–220◦C, IR spectrum ν (cm−1): 3409, 3385
(NH2) and 2929 (CH-aliphatic). Found C 66.8, H 5.1, N 15.9 and S 7.4.
Calculated for C24H23N5OS (429.54), C 67.1, H 5.4, N 16.31 and S 7.46.
MS: m/z= 429.5, 22.4%.
(13b)- yield 67%, m.p. = 226-8◦C, IR spectrum ν (cm−1): 3400, 3380
(NH2) and 2936 (CH-aliphatic). Found C 67.5, H 5.4, N 15.7, S 7.0.
Calculated for C25H25N5OS (443.57), C 67.69, H 5.68, N 15.78, S 7.23.
MS: m/z= 443.4, 22.4%.
6-Amino-11-(p-anisyl)-12H-9,10-polymethylenepyrido-
[3ꢀ ,2ꢀ :4,5]thieno[3,2-b]benzo[1,4]diazepines 14a,b
Each solution of 13a,b (0.01 mmol) in dry dioxane (60 ml) containing a
few drops of conc. HCl was heated under reflux for 6 h. The reaction mix-
ture was then cooled at room temperature and poured onto crushed ice.
The formed solid product, in each case, was filtered off and crystallized
from the proper solvent.
(14a)- yield 50%, m.p. = 240◦C (dioxane), IR spectrum ν (cm−1):
3350, 3280 (NH, NH2) and 2933 (CH-aliphatic). The 1H NMR spectrum
(DMSO-d6) δ (ppm) = 2.2–2.6 (m, 6H, 3 CH2), 3.8 (s, 3H, OCH3), 4.2 (s,
2H, NH2, D2O exchangable), 7.0–7.6 (m, 8H, aromatic protons) and 8.1
(s, 1H, NH, D2O exchangable). Found C 69.5, H 4.8, N 13.3 and S 7.7.
Calculated for C24H20N4OS (412.5), C 69.88, H 4.89, N 13.58 and S 7.77.
MS: m/z= 412.15, 18.18%.
(14b)- yield 55%, m.p. = 263◦C (dioxane), IR spectrum ν (cm−1): 3350,
3250 (NH, NH2) and 2928 (CH-aliphatic). Found C 69.9, H 5.1, N 12.7
and S 7.3. Calculated for C25H22N4OS (426.53), C 70.39, H 5.2, N 13.14
and S 7.40.

New Fused Azines
303
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