Thieno[2,3-b]pyridine-2-carbohydrazide in polyheterocyclic synthesis: The synthesis of pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine, pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]triazine, and pyrazolyl, oxadiazolylthieno[2,3-b]pyridine derivatives

Article abstract of DOI:10.1080/10426500500330828

Pyrdine-2(1H)-thione 1 reacted with ethyl chloroacetate 2 to give 2-S-ethoxy-carbonylmethylpyridine derivative 3, which could be cyclized into thieno[2,3-b]-pyridine-2-carbohydrazide derivative 5 by boiling with hydrazine hydrate. The latter compound reac

Full text of DOI:10.1080/10426500500330828

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Thieno[2,3-b]pyridine-2-
carbohydrazide in
Polyheterocyclic
Synthesis: The Synthesis of
Pyrido[3′,2′:4,5]thieno[3,2-
d]pyrimidine,
Pyrido[3′,2′:4,5]thieno[3,2-d]
[1,2,3]triazine, and Pyrazolyl,
Oxadiazolylthieno[2,3-
b]pyridine Derivatives
Mohamed A. A. Elneairy a , Mohamed A. M. Gad-
Elkareem b & Azza M. Abdel-Fattah a
a Chemistry Department, Cairo University, Giza,
Egypt
b Chemistry Department, Al-Azhar University (Assiut
branch), Assiut, Egypt
Published online: 01 Feb 2007.
To cite this article: Mohamed A. A. Elneairy , Mohamed A. M. Gad-Elkareem
& Azza M. Abdel-Fattah (2006) Thieno[2,3-b]pyridine-2-carbohydrazide in
Polyheterocyclic Synthesis: The Synthesis of Pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine,
Pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]triazine, and Pyrazolyl, Oxadiazolylthieno[2,3-
b]pyridine Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements,
181:6, 1451-1466, DOI: 10.1080/10426500500330828
To link to this article: http://dx.doi.org/10.1080/10426500500330828

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Phosphorus, Sulfur, and Silicon, 181:1451–1466, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500330828
Thieno[2,3-b]pyridine-2-carbohydrazide
in Polyheterocyclic Synthesis: The Synthesis
of Pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine,
Pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d][1,2,3]triazine, and Pyrazolyl,
Oxadiazolylthieno[2,3-b]pyridine Derivatives
Mohamed A. A. Elneairy
Chemistry Department, Cairo University, Giza, Egypt
Mohamed A. M. Gad-Elkareem
Chemistry Department, Al-Azhar University (Assiut branch),
Assiut, Egypt
Azza M. Abdel-Fattah
Chemistry Department, Cairo University, Giza, Egypt
Pyrdine-2(1H)-thione 1 reacted with ethyl chloroacetate 2 to give 2-S-ethoxy-
carbonylmethylpyridine derivative 3, which could be cyclized into thieno[2,3-b]-
pyridine-2-carbohydrazide derivative 5 by boiling with hydrazine hydrate. The lat-
ter compound reacted with cinnamonitrile derivatives 6a,b, triethylorthoformate,
formic acid, dimethylformamide-dimethylacetal, and diethyl carbonate to give the
corresponding shiff base 7a, b and pyrido[3ꢀ,2ꢀ;4,5]thieno[3,2-d]pyrimidine deriva-
tives 10–13 in respective manner. On the other hand, compound 5 also reacted with
carbondisulphide and phenyl isothiocyanate to afford the corresponding 2-(1,3,4-
oxadiazolo-2-yl)thieno[2,3-b]pyridine derivatives 18 and 22. Finally, compound 5
reacted with some β-dicarbonyl compounds, such as ethyl acetoacetate, acetylace-
tone and ethyl β-arylazoacetoacetate, to yield the corresponding 2-(pyrazol-1-yl-
carbonyl)thieno[2,3-b]pyridine derivatives 24, 25, and 27 respectively.
Keywords 2-(1,3,4-Oxadiazolo-2-yl)thieno[2,3-b]pyridine; 2-(pyrazol-1-ylcarbonyl)-
thieno[2,3-b]pyridine; pyridine-2(1H)-thiones; thieno[2,3-b]pyridine-2-carbohydrazide,
thieno[2,3-b]pyridines; pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidines
INTRODUCTION
Thieno[2,3-b]pyridines are of special importance due to the reported bi-
ological activities, such as antimicrobial,1−5 anti-inflammatory,6 and
Received June 20, 2005; accepted July 28, 2005.
Address correspondence to Mohamed A. A. Elneairy, Cairo University, Chemistry De-
partment, Faculty of Science, Giza, Egypt. E-mail: elneairy65@hotmail.com
1451

1452
M. A. A. Elneairy et al.
ganadotropin-releasing hormone antagonizing activities,7 they also
have neurotropic activity.8 Furthermore, pyridothienopyrimidines were
reported to have antiallergic,9 antiparasitic,10 antianaphylactic,11,12
and anti-microbial1,2 activities. In addition, pyridothienotriazines were
reported to have antiparasitic activity.10 The interesting biological ac-
tivities reported for these classes of compounds, and in continuation
of our efforts on the synthesis of expected biologically active hete-
rocyclic compounds utilizing thieno[2,3-b]-pyridine,4,13−20 have stimu-
lated us to investigate the reaction of thieno[2,3-b]pyridine 413 with
different reagents for the synthesis of some novel of heterocyclic
moieties.
RESULTS AND DISCUSSION
It has been found that pyridine-2(1H)-thione 1 reacted with ethyl
chloroacetate 2 in sodium methoxide solution (prepared from 1 mole
of sodium and 30 mL of methanol) to give the corresponding 2-ethoxy-
carbonylmethylthiopyridine derivative 3, which could be, in turn, cy-
clized to the 2-hyrazinocrbonylthieno[2,3-b]pyridine derivative 5 via
its reaction with hydrazine hydrate. The IR spectrum of compound 5
showed the absorption bands (3472, 3338, and 3199) corresponded to
NH2 and NHNH2; two carbonyl groups (1696.2 and 1659) corresponded
to acetyl carbonyl and hydrazidic carbonyl and did not show any absorp-
tion band attributed to the nitrile function, which could be consumed
in the reaction via the addition of the methylene group of 3 to the cyano
1
group. H-NMR of 5 revealed the signals of NH and NH2 and did not
reveal any signals attributed to the ethyl function. Moreover, the mass
spectrum of 5 gave the molecular ion peak M+ at m/z = 383 (38.9%)
and the base peak at m/z = 309 (100%) corresponding to M+ (383) −
[HN-NH2 (31) + CONH2(44)] + H (1).
The structure of compound 5 was confirmed via its synthesis by the
reaction of 4 (prepared from the reaction of 1 with 2 in the presence of
two moles of sodium methoxide in boiling methanol or by heating 3 in
ethanolic potassium hydroxide solution)13 with hydrazine hydrate (c.f.
Scheme 1, Figure 1, and Experimental section).
Compound 5 could be used as starting material to synthesize
new heterocyclic moieties, such as pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d][1,2,3]-
triazin-4-one 9a,b, pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine 10–13, im-
idazo[4ꢀ,5ꢀ:4,5]thieno[2,3-d]pyridine 16, and pyrazolo[3ꢀ,4ꢀ:4,5]thieno-
[2,3-b]pyridine 17 derivatives.
It has been found that compound 5 reacted with cinnamonitrile
derivative 6a to afford the corresponding 3-amino-Nꢀ-{[4-(dime-
thylamino)phenyl]methylene}thieno[2,3-b]pyridine-2-carbohydrazide

Thieno[2,3-b]pyridine-2-carbohydrazide
1453
SCHEME 1
derivative 7a. The IR spectrum of 7a showed absorption bands of NH
and NH2 (3457.7, 3315.1, and 3260.1), acetyl carbonyl (1697.2), and hy-
drazidic carbonyl (1632). Its 1H-NMR revealed a new signal at δ = 7.69,
which corresponded to the imino-CH proton. The reaction between 5
and 6a proceeded via a ylidene exchange with the elimination of one
molecule of malononitrile. Compound 7a could be prepared via another
route by the reaction of 5 with 4-(N,N-dimethylamino)benzaldehyde
8a, compound 7a synthesized via this route and was found to be
identical in all aspects (spectral data, m.p., and mixed m.p.) with 7a
previously prepared.
A third elucidation of the structure of compound 7a came from
its cyclization by the reaction with sodium nitrite in the presence of
concentrated hydrochloric acid21 to give the corresponding pyrido-
[3ꢀ,2ꢀ:4,5]thieno[3,2-d][1,2,3]triazinone derivative 9a. The IR spectrum
of compound 9a did not show any absorption bands that corresponded
to the NH or NH2, indicating that they were consumed in the re-
action to form the salt of diazonium chloride, which underwent self
coupling with the loss of one molecule of hydrogen chloride under
experimental reaction conditions. Moreover, its 1H-NMR spectrum
didn’t reveal any signals that corresponded to NH or NH2. Based
on the previously discussed data compound 9a could be formulated
as 3-({[4-(dimethylamino)phenyl]methylene}amino)pyrido-[3ꢀ,2ꢀ:4,5]

1454
M. A. A. Elneairy et al.
FIGURE 1 Fragmentation pattern of compound 5.
thieno[3,2-d][1,2,3]triazin-4(3H)-one derivative. In the same man-
ner, compounds 5 reacted with cinnamonitrile derivative 6b to
afford the corresponding 3-amino-Nꢀ-[(1,3-diphenyl-1H-pyrzol-4-yl)-
methylene]thieno[2,3-b]pyridine-2-carbohydrazide derivative 7b. The

Thieno[2,3-b]pyridine-2-carbohydrazide
1455
structure of compound 7b was confirmed via its synthesis by the
reaction of 5 with aromatic aldehyde 8b to give 7b. Compound 7b re-
acted with sodium nitrite in the presence of concentrated hydrochloric
acid to afford the corresponding 3-{[(1,3-diphenyl-1H-pyrzol-4-yl)-
methylene]amino}pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d][1,2,3]triazin-4(3H)-
one derivative 9b (c.f. Scheme 2 and Experimental section).
SCHEME 2
Work was also extended to shed more light on the synthetic poten-
tial of compound 5 to synthesize a new moiety of pyrido[3ꢀ,2ꢀ:4,5]thieno-
[3,2-d]pyrimidinone derivatives 10–13 by using available reagents,
such as triethylorthoformate, formic acid, dimethylformamide-
dimthylacetal (DMF-DMA), and diethyl carbonate. Thus, it has
been found that compound 5 reacted with triethylorthoformate to
give the corresponding 3-aminopyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidine

1456
M. A. A. Elneairy et al.
derivative 10. The IR of 10 showed absorption bands of amino (3310.6,
3200.4), acetyl-CO (1699.8), and pyrimidine-CO (1645.5) groups. The
1H-NMR of 10 revealed a singlet signal at δ = 5.99 that corresponded to
NH2 and a singlet signal at δ = 8.28, which corresponded to pyrimidine-
2H (c.f. Scheme 2 and Experimental section).22 Compound 10 could be
prepared via another route by the condensation of 5 with formic acid or
one mole of DMF-DMA under reflux for 3 h. Compound 10 that formed
via this route was found to be identical in all aspects as 10 was previ-
ously prepared (spectral data, m.p., and mixed m.p.). Further elucida-
tion for the structure of 10 came from its reaction with formic acid
again to yield 3-fomylaminopyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidin-4-
one derivative 11. The IR spectrum of 11 showed absorption bands
corresponded to NH (3310.9) and CO of the formyl group (1721.3). More-
over, its 1H-NMR spectrum revealed a singlet signal at δ = 8.47, which
corresponded to the aldehydic proton, and a singlet signal at δ = 11.54,
which corresponded to the NH. Compound 11 could be prepared via
another route by heating 5 with formic acid23 for 6 h (c.f. Scheme 2 and
Experimental section).
The condensation of compound 5 with excess DMF-DMA in dry xy-
lene to give the corresponding 3-{(dimethylaminomethylene)amino}-
pyrido[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidinone derivative 12. The IR spect-
rum of 12 showed absorption bands corresponded to acetyl-CO and
pyrimidine-CO groups and didn’t show any absorption band that cor-
responded to the amino group, which was consumed in the reaction.
Moreover, its 1H-NMR spectrum revealed two new singlets at δ = 8.09
and δ = 8.16, which corresponded to the pyrimidine-2H and methyne-
protons and didn’t reveal any signal that corresponded to the NH2
group. The structure of compound 12 could be confirmed via its syn-
thesis from the reaction of 10 and DMF-DMA in boiling dry xylene (c.f.
Scheme 2 and Experimental section).
Finally, due to broad biological activities of the pyrido-
[3ꢀ,2ꢀ:4,5]thieno[3,2-d]pyrimidinone moiety, compound 5 reacted with
diethyl carbonate to afford the corresponding 3-aminopyrido[3ꢀ,2ꢀ:4,5]-
thieno[3,2-d]pyrimidin-2,4-dione derivative 13. The structure of 13
was confirmed based on the elemental analysis and spectral data (c.f.
Scheme 2 and Experimental section).
The work was extended to synthesize novel heterocyclic deriva-
tives containing a five membered-ring with two nitrogen atoms. Thus,
it has been found that compound 5 reacted with a cold solution of
sodium nitrite in the presence of acetic acid to give the correspond-
ing 3-aminothieno[2,3-b]pyridine-2-carbonylazide derivative 14. The IR
spectrum of 14 showed the new absorption band at 2137.6, which was
attributed to the azide22,23 function and NH2 (3473.7 and 3321.2). Its

Thieno[2,3-b]pyridine-2-carbohydrazide
1457
1H-NMR revealed a singlet signal at δ = 10 ppm, which corresponded
to NH2 and did not reveal any signals that may be attributed to the
NHNH2 protons, which were consumed in the formation of the azide
function.22,23 Further confirmation of structure 14 came from its cycliza-
tion in dry xylene into the corresponding imidazo[4ꢀ, 5ꢀ : 4, 5]thieno-
[2,3-b]pyridine derivative 16. Compound 16 was formed via a Curtius
rearrangement22,23 of compound 14 into isocyanate 15 followed by a nu-
cleophilic addition of the NH2 function of 15 to the N C O to yield the
novel condensed imidazole 16. The IR spectrum of 16 showed new ab-
sorption bands of two NH and CO groups of a new imidazole moiety and
absence of any absorption band due to the azide function. The 1H-NMR
spectrum of the latter compound revealed new signals at δ = 9.38, and
δ = 11.08, which corresponded to the two NH protons (c.f. Scheme 3 and
Experimental section).
SCHEME 3
A new pyrazolo[3ꢀ,4ꢀ:4,5]thieno[2,3-b]pyridine derivative 17 was
formed via the treatment of 5 with glacial acetic acid under reflux for
4 h, the structure of the latter compound was elucidated based on the
elemental analysis and spectral data (c.f. Scheme 3 and Experimental
section).
In continuation of the present work, compound 5 reacted with sulfur-
containing compounds, such as carbon disulphide and phenylisothiocy-
nate, to synthesize new heterocyclic rings such as 2-(1,3,4-oxadiazolo-
2-yl)thieno[2,3-b]pyridine derivatives 18–20, 22 respectively. Thus, it
has been found that compound 5 reacted with carbon disulphide
in pyridine to give the corresponding 3-amino-2-(5-mercapto-1,3,4-
oxadiazol-2-yl)thieno[2,3-b]pyridine derivative 18. The structure of 18

1458
M. A. A. Elneairy et al.
was inferred by elemental analysis and chemical transformation. The
1H-NMR spectrum of compound 18 revealed a new signal at δ = 7.35,
which corresponded to the -SH proton. The reaction of 18 with hy-
drazine hydrate afforded the corresponding 3-amino-2-(5-hydrazino-
1,3,4-oxadiazol-2-yl)thieno[2,3-b]pyridine derivative 19 via the loss of
one molecule of hydrogen sulfide. The latter compound was further con-
firmed via its reaction with sodium nitrite in the presence of concen-
trated hydrochloric acid to give the corresponding 3-amino-2-(5-azido-
1,3,4-oxadiazol-2-yl)thieno[2,3-b]pyridine derivative 20. The structure
of compounds 18–20 was confirmed based on the elemental analysis
and spectral data. (c.f. Scheme 4 and Experimental section).
SCHEME 4
On the other hand, compound 5 reacted with phenylisothiocyanate
to give the corresponding 3-amino-2-(5-phenylamino-1,3,4-oxadiazol-2-
yl)thieno[2,3-b]pyridine derivative 22 via the loss of one molecule of
hydrogen sulfide through the formation of the intermediate 21. (c.f.
Scheme 4 and Experimental section).
Finally, compound 5 reacted with different β-dicarbonyl compounds
to form 2-(pyrazol-2-yl)thieno[2,3-b]pyridine derivative 23, 26, and 27.
Thus, it has been found that compound 5 reacted with ethyl acetoacetate
in boiling glacial acetic acid and gave the corresponding 2-(pyrazol-1-
yl)thieno[2,3-b]pyridine derivative 23 or 24. The IR spectrum of the
reaction product showed absorption bands corresponded to amino and
carbonyl groups and didn’t show any absorption band attributed to

Thieno[2,3-b]pyridine-2-carbohydrazide
1459
the hydroxyl group. Moreover, its 1H-NMR revealed a singlet signal at
δ = 2.29 that corresponded to the pyrazolyl-CH2 and absence of any sig-
nals that corresponded to the OH or CH of the pyrazole moietyl. Based
on the previously discussed data the reaction product was formulated
as 5-acetyl-3-amino-4-(4-dimethylaminophenyl)-2-[carbonyl(3-methyl-
4,5-dihydro-5H-pyrazol-5- on-1-yl)]-6-methylthieno[2,3-b]pyridine 23
and not the enol form 24 (c.f. Scheme 5 and Experimental
section).
SCHEME 5
In the same manner, compound 5 reacted with acetylacetone and
ethyl 2-arylazoacetoacetate to give the corresponding 2-(pyrazol-1-yl)-
thieno[2,3-b]pyridine derivative 26 and the hydrazo form 2-(4-phenyl-
hydrazonopyrazol-1-yl)thieno[2,3-b]pyridine derivative 27 based on the
elemental analyses and spectral data (c.f. Scheme 5 and Experimental
section).
EXPERIMENTAL
All melting points were measured on a Gallenkamp electrothermal
melting point apparatus and are uncorrected. The infrared spectra
were recorded in potassium bromide on Pye Unicam SP 3-300 infrared
1
and FT-IR 8101PC Schimadzu spectrophotometer. The H-NMR spec-
tra were recorded in deutrated chloroform or dimethyl sulphoxide on a

1460
M. A. A. Elneairy et al.
Varian Gemini 200 NMR and varian Mercury 300 MHz spectrometer
using tetramethylsilane (TMS) as an internal reference; mass spectra
were recorded on GCMS-QP 1000 EX Shimatzu mass spectrometer at
70 eV. Elemental analyses were carried out at the Microanalytical Cen-
ter of Cairo University, Giza, Egypt.
Compound 1 and 4 were prepared according to the literature
procedure.13
The Synthesis of 3
A solution of each of 1 (0.01 mol) and ethyl chloroacetate 2 (0.01 mol)
in sodium methoxide (prepared from 0.01 g of sodium and 30 mL of
methanol) was heated under reflux for 4 h, cooled, poured onto ice cold
water, and neutralized (pH = 7) with concentrated hydrochloric acid,
the solid was collected by filtration, dried, and crystallized from dioxane
to give 3 (c.f. Tables I and II).
The Synthesis of 5 and 19
A solution of each of 3 or 4 and 18 (0.01 mol) in hydrazine hydrate (15
mL) and ethanol (20 mL) was heated under reflux for 6 h; the excess
solvents were evaporated in vacuo (to 1/3 of the solution) and cooled.
The solid was collected by filtration, dried, and crystallized from the
proper solvent to give 5 and 19, respectively (c.f. Tables I and II).
The Synthesis of 7a,b
Method A
A solution of each of 5 (0.01 mol) and cinnamonitrile derivatives 6a,
b (0.01 mol) in pyridine (15 mL) and ethanol (20 mL) was heated under
reflux for 2 h, the excess solvents were evaporated in vacuo (to 1/3 of
the solution) and cooled, the solid was collected by filtration, dried, and
crystallized from the acetic acid to give 7a, b respectively (c.f. Tables I
and II).
Method B
A solution of each of 5 (0.01 mol) and aromatic aldehydes 8a, b (0.01
mol) in pyridine (15 mL) and ethanol (20 mL) was heated under reflux
for 2 h. Excess solvents were evaporated in vacuo (to 1/3 of the solution)
and cooled, the solid was collected by filtration, dried, and crystallized
from the acetic acid to give 7a, b respectively (c.f. Tables I and II).

Thieno[2,3-b]pyridine-2-carbohydrazide
1461
TABLE I Elemental Analyses of the Newly Synthesized Compounds
Mol.
formula/
mol. wt.
Solvent
of cry.
yield %
Analyses calc./found
Compound
no.
Colour/
m.p.◦C
C
H
N
S
3
C21H23N3O3S
397.50
Dioxane
70
Ethanol
75
Yellow
167–169
Yellow
236–238
Yellow
296–298
Yellow
288–290
Yellow
230–232
Yellow
222–224
Yellow
266–268
Yellow
180–182
Yellow
279–281
Yellow
318–320
Brown
180–182
Brown
>300
63.46 5.83 10.57
63.20 6.10 10.90
59.51 5.52 18.26
59.80 5.80 18.50
65.35 5.88 16.33
65.00 5.50 16.50
68.50 5.09 15.98
68.20 4.90 15.70
63.98 5.18 18.65
63.80 5.10 18.30
67.29 4.52 17.94
67.50 4.40 17.90
61.05 4.87 17.80
61.00 4.70 17.70
59.84 4.54 16.62
59.60 4.40 16.40
61.59 5.39 18.74
61.40 5.50 18.70
58.67 4.68 17.10
58.30 4.30 17.00
57.85 4.60 21.31
57.70 4.30 21.20
60.70 3.60 16.66
60.50 3.40 16.50
62.28 4.95 15.29
61.90 5.00 15.10
8.07
7.9
8.36
8.1
5
C
19H21N5O2S
383.48
7a
7b
9a
9b
10
11
12
13
14
16
17
18
19
20
22
23
26
27
C28H30N6O2S Acetic acid
514.65 69
35H31N7O2S Acetic acid
6.23
6.60
5.22
5.00
6.10
5.90
5.13
5.00
8.15
8.10
7.61
7.40
7.15
7.30
7.83
7.60
8.13
8.20
9.53
9.40
8.75
8.60
C
C
C
C
613.75
28H27N7O2S
525.64
35H28N8O2S
624.73
78
Dioxane
85
Dioxane
75
20H19N5O2S
393.47
Ethanol
73
C21H19N5O3S Acetic acid
421.48
23H24N6O2S
448.55
20H19N5O3S
409.47
71
Dioxane
68
Ethanol
67
Ethanol
79
DMF/H2O
76
C
C
C19H18N6O2S
394.46
C17H12N4O2S
336.37
C19H18N4O2S Acetic acid
Yellow
290–292
366.44
20H19N5O2S2
425.53
74
Ethanol
75
Dioxane
76
Dioxane
75
Ethanol
81
C
Pale/Brown 56.45 4.50 16.46 15.07
284–286
Yellow
236–238
Yellow
>330
Brown
168–170
Yellow
>320
Yellow
250–252
Brown
276–178
56.10 4.30 16.40 15.10
C20H21N7O2S
56.72 5.00 23.15
56.50 4.90 23.00
55.29 4.18 25.79
55.60 4.50 25.70
64.44 4.99 17.34
64.20 4.80 17.10
61.45 5.16 15.58
61.20 5.30 15.60
64.41 5.63 15.65
64.30 5.60 16.50
62.91 4.92 17.71
62.70 5.22 17.50
7.57
7.30
7.38
7.50
6.62
6.50
7.13
7.40
7.16
6.90
5.79
5.60
423.50
C
20H18N8O2S
434.476
C26H24N6O2S
484.58
C23H23N5O3S Acetic acid
449.54 73
24H25N5O2S Acetic acid
447.56 79
29H27N7O3S Acetic acid
553.65 70
C
C
The Synthesis of 9a,b, 14, and 20
A stirred solution (0–5◦C) of the appropriate of thieno[2,3-b]pyridine
derivatives 7a, b, 5, and 19 (0.01 mol) in acetic acid (20 mL) and

1462
M. A. A. Elneairy et al.
TABLE II IR (cm−1) and 1H-NMR Spectra of Newly Synthesized
Compounds
Compound
no.
IR (cm−1
)
1H-NMR δ (ppm)
3
5
2218.7 (CN) and 17461,
1694.4 (two C O)
CDCl3, 1.19 (t, 3H, CH2CH3), 1.80 (s, 3H, CH3),
2.34 (s, 3H, COCH3), 2.97 (s, 6H, N(CH3)2),
3.71 (s, 2H, -SCH2), 3.91 (q, 2H, CH2CH3),
6.73 (d, J = 8.8 Hz, 2H, Ar-H) and 7.15 (d, J =
8.8 Hz, 2H, Ar-H)
CDCl3, 1.88 (s, 3H, CH3), 2.48 (s, 3H, COCH3),
2.97 (s, 6H, N(CH3)2), 3.64–4.09 (br. 3H,
NHNH2), 5.78 (br. 2H, NH2), 6.68 (d, J = 8.4
Hz, 2H, Ar-H) and 7.08 (d, J = 8.4 Hz, 2H,
Ar-H)
3472.1, 3338.4, 3199.5
(NH & NH2) and
1696.2, 1659 (two C O)
7a
7b
9a
3475.7, 3315.1, 3260.1
(NH2 & NH) and
1697.2, 1632 (two C O)
CDCl3, 1.9 (s, 3H, CH3), 2.57 (s, 3H, COCH3),
2.99 (s, 12H, two N(CH3)2), 6.72 (d, J = 8.7 Hz,
2H, Ar-H), 6.90 (2H, s, NH2), 7.13 (d, J = 8.7
Hz, 2H, Ar-H), 7.69 (s, 1H, CH) and 7.72 (NH)
DMSO-d6, 1.89 (s, 3H, CH3), 2.55 (s, 3H,
COCH3), 2.80 (s, 6H, N(CH3)2), 6.81 (2H, s,
NH2), 7.16-7.61 (m, 14H, Ar-H), 8.0 (s, 1H,
CH), 8.21 (s, 1H, CH) and 8.90 (s, 1H, NH)
3475.7, 3315.1, 3260.1
(NH2 & NHNH2) and
1697.2, 1632 (two C O)
1696.5, 1661.9 (two C O) DMSO-d6, 2.13 (s, 3H, CH3), 2.56 (s, 3H,
COCH3), 2.93 (s, 12H, two N(CH3)2), 7.26 (d, J
= 8.3 Hz, 2H, Ar-H), 7.50 (d, J = 8.3 Hz, 2H,
Ar-H) and 7.84 (s, 1H, CH)
9b
10
1696.5, 1661.9 (two C O) CDCl3, 2.02 (s, 3H, CH3), 2.62 (s, 3H, COCH3),
3.04 (s, 6H, N(CH3)2), 7.18–7.76 (m, 14H,
Ar-H), 8.47 (s, 1H, CH) and 8.78 (s, 1H, CH)
3310.6, 3200.4 (NH2) and DMSO-d6, 1.89 (3H, s, CH3); 2.54 (3H, s,
1699.8, 1645.5 (two
O)
COCH3); 2.99 (6H, s, N(CH3)2); 5.99 (2H, s,
NH2); 6.75 (d, J = 8.1 Hz, 2H, Ar-H), 7.14 (d, J
= 8.1 Hz, 2H, Ar-H) and 8.28 (1H, s, CH- at
pyrimidine)
C
11
12
13
3214.4 (NH) and 1721.3, DMSO-d6, 1.9 (s, 3H, CH3), 2.50 (s, 3H, COCH3),
1678.2, 1610.9 (three
O)
2.99 (s, 6H, N(CH3)2), 6.75 (d, J = 8.2 Hz, 2H,
Ar-H), 7.14 (d, J = 8.2 Hz, 2H, Ar-H), 8.28 (s,
1H, CH- at pyrimidine), 8.47 (s,1H, CHO) and
11.54 (s,1H, NH)
C
1695.9, 1669.4 (two C O) DMSO-d6, 1.89 (3H, s, CH3); 2.54 (3H, s,
COCH3); 2.99 (12H, s, -N(CH3)2); 6.74 (d, J =
8.7 Hz, 2H, Ar-H), 7.14 (d, J = 8.7 Hz, 2H,
Ar-H), 8.09 (1H, s, -N=CH-) and 8.16 (1H, s,
CH- at pyrimidine)
3459.9, 3301.33193 (NH2 DMSO-d6, 1.89 (s, 3H, CH3), 2.43 (s, 3H,
& NH) and 1687.8,
1650 (C O)
COCH3), 2.98 (s, 6H, N(CH3)2), 4.41 (2H, s,
NH2), 6.84 (d, J = 8.5 Hz, 2H, Ar-H) and 7.16
(d, J = 8.5 Hz, 2H, Ar-H) and 12.15 (s, 1H, NH)

Thieno[2,3-b]pyridine-2-carbohydrazide
1463
TABLE II IR (cm−1) and 1H-NMR Spectra of Newly Synthesized
Compounds (Continued)
Compound
no.
IR (cm−1
)
1H-NMR δ (ppm)
14
16
3473.7, 3321.2 (NH2);
2137.6 (azide N3) and
1688, 1642 (two C O)
DMSO-d6, 1.9 (s, 3H, CH3), 2.51 (s, 3H, COCH3),
3.0 (s, 6H, N(CH3)2), 7.67 (d, J = 7.8 Hz, 2H,
Ar-H), 7.67 (d, J = 7.8 Hz, 2H, Ar-H) and 10.0
(2H, s, NH2)
DMSO-d6, 1.90 (s, 3H, CH3), 2.50 (s, 3H,
COCH3), 3.01 (s, 6H, N(CH3)2), 6.86 (d, J =
8.4 Hz, 2H, Ar-H), 7.11 (d, J = 8.4 Hz, 2H,
Ar-H), 9.38 (s, 1H, NH) and 11.08 (s, 1H,
NH).
3397.6 (two NH) and
1695.4, 1662.5 (two
C
O)
17
18
3221.4 (two NH) and
1724.3, 1681.9 (two
CDCl3, 1.88 (s, 3H, CH3), 2.4 (s, 3H, COCH3),
2.98 (s, 6H, N(CH3)2), 4.85 (s, 1H, NH), 6.73
(d, J = 8.4 Hz, 2H, Ar-H), 7.17 (d, J = 8.4 Hz,
2H, Ar-H), and 8.86 (s, 1H, NH).
DMSO-d6, 1.84 (s, 3H, CH3), 2.55 (s, 3H,
COCH3), 2.58 (s, 2H, NH2), 2.99 (s, 6H,
N(CH3)2), 6.63 (d, J = 8.7 Hz, 2H, Ar-H), 7.11
(d, J = 8.7 Hz, 2H, Ar-H) and 7.35 (s, 1H,
-SH)
C
O)
3407, 3259.3 (NH2) and
16997, 1664.9 (two
C
O).
19
20
22
23
26
3303.1, 3183.4 (NH &
NH2) and 1695.4,
1667.2 (C O)
DMSO-d6, 1.86 (s, 3H, CH3), 2.50 (s, 3H,
COCH3), 2.91 (s, 6H, N(CH3)2), 4.08-4.56 (br,
4H, two NH2) and 6.63-7.5 (m, 5H, Ar-H &
NH)
3474, 3350 (NH2), 2147.4 DMSO-d6, 1.90 (s, 3H, CH3), 2.60 (s, 3H,
(azide N3) and 1697.8
(C O)
COCH3), 2.98 (s, 6H, N(CH3)2), 3.40 (s, 2H,
NH2), 6.78 (d, J = 8.6 Hz, 2H, Ar-H) and 7.32
(d, J = 8.6 Hz, 2H, Ar-H)
3350.2 (NH) and 1695.9 CDCl3, 1.93 (s, 3H, CH3), 2.58 (s, 3H, COCH3),
(C O)
2.96 (s, 6H, N(CH3)2), 3.09 (s, 2H, NH2),
6.77-7.42 (m, 11H, Ar-H & NH2) and 9.89 (s,
1H, NH)
3377.4 (OH) and 1692.7
(C O)
CDCl3, 2.0 (s, 6H, two CH3), 2.29 (s, 2H, CH2),
2.57 (s, 3H, COCH3), 3.03 (s, 6H, N(CH3)2),
5.58 (s, 2H, NH2), 6.84 (d, J = 8.4 Hz, 2H,
Ar-H) and 7.19 (d, J = 8.4 Hz, 2H, Ar-H)
DMSO-d6, 1.34 (s, 3H, CH3), 1.88 (s, 3H, CH3),
1.91 (s, 3H, CH3), 2.43 (s, 3H, COCH3), 2.95 (s,
6H, N(CH3)2), 3.53 (s, 2H, NH2), 6.72 (d, J =
8.8 Hz, 2H, Ar-H), 6.97 (d, J = 8.8 Hz, 2H,
Ar-H) and 9.12 (s, 1H, 4H-pyrazole)
3425.9, 3265 (NH2) and
1698.8, 1659 (two C O)
27
3473.9, 3319.9 (NH2) and CDCl3, 1.91 (s, 3H, CH3), 2.51 (s, 3H, CH3), 2.57
1696.2, 1638.1 and
1608.3 (three C O)
(s, 3H, COCH3), 2.91 (s, 2H, NH2), 3.01 (s, 6H,
N(CH3)2), 6.78 (d, 2H, Ar-H), 7.15 (s, 1H, NH)
and 7.51-7.65 (m, 9H, Ar-H)

1464
M. A. A. Elneairy et al.
concentrated hydrochloric acid (3 mL) was treated with a cold solu-
tion of sodium nitrite (0.23 g in 5 mL of water) over 5 min. Stirring
was continued for 1 h at 0–5◦C; the solid was collected by filtration,
dried, and crystallized from the proper solvent to give 9a, b, 14, and
20, respectively (c.f. Tables I and II).
The Synthesis of 10
Method A
A solution of each of 5 (0.01 mol) and triethylorthoformate (10 mL)
was heated under reflux for 4 h; the excess solvent was evaporated in
vacuo (to 1/3 of the solution) and cooled. The solid was collected by
filtration dried, and crystallized from ethanol to give 10 (c.f. Tables I
and II).
Method B
A solution of each of 5 (0.01 mol) and formic acid (20 mL) or DMF-
DMA (0.01 mol) was heated under reflux for 3 h. The excess solvent
was evaporated in vacuo (to 1/3 of the solution) and cooled; the solid
was collected by filtration, dried, and crystallized from ethanol to give
10 (c.f. Tables I and II).
The Synthesis of 11
A solution of each of 5 or 10 (0.01 mol) and formic acid (30 ml) was heated
under reflux for 6 h. The excess solvent was evaporated in vacuo (to 1/3
of the solution) and cooled; the solid was collected by filtration, dried,
and crystallized from the proper acetic acid to give 11 (c.f. Tables I and
II).
The Synthesis of 12
A solution of each of 5 or 10 (0.01 mol) and dimethylformamaide-
dimethylacetal (0.025 mol) in dry dioxane (30 mL) was heated under
reflux for 6 h. The excess solvent was evaporated in vacuo (to 1/3 of the
solution) and cooled; the solid was triturated with petroleum ether and
collected by filtration, dried, and crystallized from dioxane to give 12
(c.f. Tables I and II).
The Synthesis of 13
A solution of each of 5 and diethyl carbonate (30 mL) was heated under
reflux for 5 h. The excess solvent was evaporated in vacuo(to 1/3 of the

Thieno[2,3-b]pyridine-2-carbohydrazide
1465
solution) and cooled; the solid was collected by filtration, dried, and
crystallized from ethanol to give 13 (c.f. Tables I and II).
The Synthesis of 16
A solution of 14 in dry xylene (30 mL) was heated under reflux for 5 h.
The excess solvent was evaporated in vacuo (to 1/3 of the solution) and
cooled. The solid was triturated with petroleum ether and collected by
filtration, dried, and crystallized from DMF/H2O (2:1) to give 16 (c.f.
Tables I and II).
The Synthesis of 17
A solution of 5 in acetic acid (30 mL) was heated under reflux for 5 h.
The excess solvent was evaporated in vacuo (to 1/3 of the solution) and
cooled. The solid was collected by filtration, dried, and crystallized from
acetic acid to give 17 (c.f. Tables I and II).
The Synthesis of 18 and 22
A solution of 5 (0.01 mol) and either carbon disulphide (5 mL) or
phenylisothiocyanate (0.01 mol) in pyridine (30 mL) was heated un-
der reflux for 5 h, cooled, poured onto ice-cold water, and neutralized
(pH = 7) with hydrochloric acid; the solid was collected by filtration,
dried, and crystallized from the ethanol to give 18 or 22 (c.f. Tables I
and II).
The Synthesis of 23, 26, and 27
A solution of 5 and either ethyl acetoacetate, acetylacetone, or 2-
phenylazoethylacetoacetate (0.01 mol) in acetic acid (30 mL) was heated
under reflux for 5 h. The excess solvent was evaporated in vacuo (to 1/3
of the solution) and cooled; the solid was collected by filtration, dried
and crystallized from the acetic acid to give 23, 26 or 27 (c.f. Tables I
and II).
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