Reactions of hydrazonoyl halides 43 [1]: Synthesis of some new 2,3-dihydro-l,3,4-thiadiazoles, pyrazoles, pyrazolo[3,4-d]-pyridazines, thieno[2,3-b]pyridines, pyrimidino[4′,5′:4,5]thieno[2,3-b]-pyridines and pyrrolo[3,4-d]pyrazoles

Article abstract of DOI:10.1002/jhet.5570420409

2,3-Dihydro-1,3,4-thiadiazoles, pyrazoles, pyrazolo[3,4-d]pyridazines, thieno[2,3-b]pyridines, pyrimidino[4′,5′:4,5]thieno[2,3-b]pyridines and pyrrolo[3,4-d]pyrazoles were obtained in a good yields by treatment of hydrazonoyl halides with each of alkyl carbodithioates,3-(dimethylamino)-1- naphtho[1,2-d]furan-2-ylprop-2-en-1-one and N-arylmalemides.

Full text of DOI:10.1002/jhet.5570420409

Reactions of Hydrazonoyl Halides 43 [1]: Synthesis of Some
New 2,3-Dihydro-1,3,4-thiadiazoles, Pyrazoles, Pyrazolo[3,4-d]-
pyridazines, Thieno[2,3-b]pyridines, Pyrimidino[4',5':4,5]thieno[2,3-b]-
pyridines and Pyrrolo[3,4-d]pyrazoles
May-Jun 2005
527
Abdou O. Abdelhamid* and Mohamed A. M. Alkhodshi
Department of Chemistry, Faculty of Science, Cairo University, Giza 12316, Egypt
Abdou_abdelhamid@yahoo.com
Received September 2, 2004
2,3-Dihydro-1,3,4-thiadiazoles, pyrazoles, pyrazolo[3,4-d]pyridazines, thieno[2,3-b]pyridines, pyrim-
idino[4',5':4,5]thieno[2,3-b]pyridines and pyrrolo[3,4-d]pyrazoles were obtained in a good yields by treat-
ment of hydrazonoyl halides with each of alkyl carbodithioates, 3-(dimethylamino)-1-naphtho[1,2-d]furan-
2-ylprop-2-en-1-one and N-arylmalemides.
J. Heterocyclic Chem., 42, 527 (2005).
1,3,4-Thiadiazoles are active in many biological systems
of thiohydrazonate 5, which undergoes intramolecular
cyclization as soon as it is formed to yield the interme-
diate 6 or via 1,3-dipolar cycloaddition of nitrilimine 8,
which prepared in situ from 4 with triethylamine, to
C=S double bond of 3 to give the intermediate 6.
Intermediate 6 is converted to the final product 7 via
elimination of methyl mercaptane.
such as: antitumor [2], hypoglycemic properties [3], anti-
histamine [4] and anticholinergic [5]. Pyrazoles and
annelated pyrazoles have long been known to exhibit
diverse biological activities. Among these activities
include their use as antipyretic [6], analgesic drugs [7-9],
antitumor [10], hypnotic [11], fungicides [12] and herbici-
dal [13] agents. Moreover thienopyridines are of special
importance due to reported biological activities [14]. Also
hydrazonoyl halides have been widely used for the synthe-
sis of heterocyclic compounds [15-19]. We report here the
synthesis of some new 2,3-dihydro-1,3,4-thiadiazoles,
pyrazoles, pyrazolo[4,3-d]pyridazines, thieno[2,3-b]-
pyridines, pyrimidino[4',5':4,5]thieno[2,3-b]pyridines and
pyrrolo[4,3-d]pyrazoles.
Similarly, 2-hydroxynaphthaline-1-carboxyaldehyde
reacted with methyl- or benzyl hydrazinecarbodithioate
(10a,b) to give alkyl N'-(2-hydroxynaphthalin-1-yl-
methylene)hydrazinecarbodithioates 11a and 11b, respec-
1
tively. H NMR spectrum of 11a showed signals at δ =
2.61 (s, 3H), 7.12 (d, 1H), 7.40-7.95 (m, 4H), 8.74 (d,
1H), 9.12 (s, 1H), 11.08 (s, 1H) and 13.40 (s, 1H).
Treatment of each of 11a or 11b with the appropriate
hydrazonoyl halides 4b-h in ethanol containing triethyl-
amine afforded the 5-substituted 3-aryl-2-(hydroxynaph-
thaline-1-ylmethylenehydrazino)-2,3-dihydro-1,3,4-thia-
diazoles 12b-h, respectively (Scheme 2 ).
Results and Discussion.
Treatment of methyl hydrazinecarbodithioate (2) [20]
with 1-naphtho[1,2-d]furan-2-ylethan-1-one (1) in
2-propanol afforded methyl N'-(naphtha[1,2-d]furan-2-
On the other hand, 1 reacted with DMF-DMA 13
under reflux to give 3-(dimethylamino)-1-naphtho[1,2-
1
ylethylidine)hydrazinecarbodithioate (3). The H NMR
1
spectrum of 3 showed signals at δ = 2.55 (s, 3H), 2.62
(s, 3H), 7.56-8.38 (m, 7H) and 12.52 (s, br., 1H).
Compound 3 reacted with the appropriate hydrazonoyl
halides 4a-h in ethanolic triethylamine at room temper-
ature to give 5-substituted 2-naphtho[1,2-d]furan-2-
ylethylidene-3-phenyl-1,3,4-thiadiazoline 7a-h, respec-
tively (Scheme 1). Structure 7 was confirmed by ele-
mental analysis, spectral data and alternative synthesis
d]furan-2-ylprop-2-en-1-one (14). H NMR spectrum of
14 showed signals at δ = 2.97 (s, 3H), 3.15 (s, 3H), 5.89
(d, 1H), 7.50-7.96 (m, 7H) and 8.16 (d, 1H). Thus,
C-methoxycarbonyl-N-phenylhydrazonoyl chloride 4a
and 14 was refluxed in toluene containing triethylamine
afforded, one isolable product according to tlc, methyl
4-(naphtho[1,2-d]furan-2-ylcarbonyl)-4-phenylpyra-
1
zole-3-carboxylate (17a) (Scheme 3). The H NMR
1
route. Thus, H NMR spectrum of 7b showed signals at
spectrum of 17a showed signals at δ = 3.81 (s, 3H,
δ = 1.42 (t, 3H), 1.93 (s, 3H), 4.46 (q, 2H) and 7.26-8.16
(m, 12H). Also, treatment of ethyl 2-hydrazino-3-
phenyl-2,3-dihydro-1,3,4-thiadiazole-5-carboxylate (9)
[21] with 1 in 2-propanol afforded product identical
with 7b.
OCH ), 7.27-8.21 (m, 12H, ArH's) and 8.55 (s, 1H,
3
pyrazole C-5). Compound 17a was converted to 4-naph-
tho[1,2-d]furan-2-yl-2-phenyl-6-hydropyrazolo[3,4-
d]pyridazin-7-one (19a) by refluxing with hydrazine
1
hydrate in ethanol. The H NMR spectrum of 19a
In the light of the foregoing results, the mechanism
outlined in Scheme 1 seems to be the most plausible
pathway for the formation of 7 from the reaction
between 3 and 4. The reaction involves initial formation
showed signals at δ = 7.33-7.62 (m, 12 H, ArH's), 8.23
(s, 1H, pyrazole C-5) and 11.12 (s, br., 1H, NH).
Also, 17b and 17c were refluxed with hydrazine hydrate
in ethanol to give product identical with 19a. Formation of

528
A. O. Abdelhamid and M. A. M. Alkhodshi
Vol. 42
pyridine (or in ethanol containing catalytic amount of
piperdine) gave 6-naphtho[1,2-d]furan-2-yl-2-sul-
fanylpyridine-3-carbonitrile (20). Compound 20 reacted
with iodomethane in presence of potassium hydroxide to
afford 2-methylthio-6-naphtho[1,2-d]furan-2-ylpyridine-
3-carbonitrile (21). IR spectrum of 21 revealed a band at
1
2219 (CN) and its H NMR spectrum showed signals at δ
=2.75 (s, 3H), 7.53-8.23 (m, 9H) ppm.
Treatment of 20 with ethyl chloroacetate in N,N-
dimethylformamide containing potassium hydroxide to
afford ethyl 2-(3-cyano-6-naphtho[2,1-d]furan-2-yl-2-
pyridylthio) acetate (22a) via addition and dehydrochlori-
nation reactions. The IR spectrum of this product showed
1
bands at 2214 (CN) and 1735 (CO) groups. Its H NMR
spectrum revealed signals at δ = 1.28 (t, 3H, CH CH ),
2
3
4.07 (s, 2H, SCH ), 4.28 (q, 2H, CH CH ) and 7.54-8.25
2
3
2
(m, 9H, ArH's). Further confirmation of the structure of
22a arose from their cyclization in boiling ethanol contain-
ing catalytic amount of piperidine to give the correspond-
ing thieno[2,3-b]pyridine 23a (Scheme 4). The IR spec-
trum of 23a showed no bands of the CN function while the
17 can be explained via reaction of nitrileimine 8 with 14
to afford cyclo adduct intermediate 15 or 16, and then
elimination of diethylamine to give pyazole as final prod-
uct 17 or pyrazole 18. The latter was ruled out on the basis
of the foregoing data.
bands at 3294, 3201 the new NH group. On the other
2
1
Compound 14 was refluxed with cyanothioacetamide in
hand, the H NMR spectrum of 23a revealed absence of

May-Jun 2005
Reactions with Hydrazonoyl Halides 43
529
signal of the -SCH - group and the presence of signals at δ
2
= 1.34 (t, 3H), 4.24 (q, 2H), 6.63 (s, br., 2H) and 7.57-8.69
(m, 9H). The above findings proved that the CN and the
–SCH groups were both involved in the cyclization step
2-
leading to 23a.
Similarly, compound 20 reacted also with chloroacetone
to afford 6-naptho[1,2-d]furan-2yl-2-(2-oxopropylthio)-
pyridine-3-carbonitrile 22b. The reaction seemed to pro-
ceed through dehydrochlorination to give 22b, which
underwent cyclization via addition of the SCH - hydro-
2
1
gens to the nitrile function to give 23b. IR, H NMR, and
elemental analyses were the basis on which the structure of
23b was established (Tables 1 and 2).
Similarly, compound 20 reacted with chloroacetoni-
trile to give 2-(cyanomethylthio)-6-naphtho[1,2-d]furn-
2-oylpyridine-3-carbonitrile (22c). Compounds 22c was
converted to 3-amino–6-naphtho[1,2-d]furan-2-ylth-
ieno[2,3-b]pyridine-2-carbonitrile (23c) by boiling in
ethanol containing catalytical amount of piperidine
(Tables 1 and 2). Compound 23c reacted with each of
formic acid and formamide to give the corresponding 7-
naphtho[1,2-d]furan-2-yl-3-pyrimidino[4',5':4,5]thieno-
[2,3-b]pyridine-4-one (24a) and 7-naphtho[1,2-d]furan-
2-yl-3-pyrimidino[4',5':4,5]thieno[2,3-b]pyridine-4-
ylamine (24b), respectively (Scheme 4). IR spectrum of
24a revealed band at 1674(CO) and IR spectrum of 24b
revealed bands at 3340, 3232 (NH ).
2
Hydrazonoyl bromide 4h with the appropriate N-
arylmaleimide [21] 25a-d was refluxed in toluene con-
taining triethylamine yielded 5-aryl-3-naphtho[1,2-
d]furan-2-ylcarbonyl)-1-phenyl-3a,6a-dihydro-1H-
pyrrolidino[3,4-d]pyrazole-4,6-diones 26a-d, respec-
tively (Scheme 5). IR spectra of 26a-d revealed bands
-1
-1
at 1790-1716 cm and 1710-1690 cm due to (-CO-
1
NR-CO) [22]. H NMR spectrum of 26a showed

530
A. O. Abdelhamid and M. A. M. Alkhodshi
Vol. 42
Table 1
Characterization Data of the Newly Synthesized Compounds
Comp.
No.
Mp.,°C
Solvent
Color
Yield %
Mol. Formula Calcd./Found %
Mol.Wt.
N OS
2
C
H
N
S
3
180-82
AcOH
116-17
EtOH
Yellowish brown
C
C
C
C
C
C
H
61.11
61.23
65.14
65.07
65.77
65.65
69.17
69.00
67.59
67.72
71.29
71.30
65.57
65.70
73.59
73.82
72.65
72.50
56.49
56.60
64.74
64.50
63.14
63.00
67.08
67.60
65.65
65.56
64.93
64.70
63.14
63.10
71.98
72.10
71.10
71.20
65.65
65.40
76.96
76.85
72.71
72.65
73.16
73.06
76.13
76.34
75.77
75.87
78.72
78.62
72.31
72.43
80.47
80.52
78.93
79.05
73.00
73.28
76.58
76.72
79.43
79.20
4.48
4.35
4.10
4.00
4.42
4.40
4.20
4.35
4.25
4.13
4.13
4.25
3.67
3.74
4.12
3.95
3.83
3.70
4.37
4.30
4.57
4.32
4.34
4.43
4.11
4.23
4.50
4.27
4.15
3.90
3.53
3.30
4.03
3.90
3.73
3.82
4.51
4.70
5.69
5.72
4.06
3.90
4.42
4.23
4.18
4.22
4.23
4.15
4.10
3.95
3.59
3.69
4.09
4.10
3.78
3.87
3.72
3.95
4.28
4.17
4.13
3.90
8.90
9.12
20.39
20.27
7.24
7.42
7.02
6.90
6.37
6.45
7.52
7.61
6.56
6.67
12.97
13.14
5.95
6.22
5.54
5.40
23.20
21.92
18.19
17.93
7.66
7.82
6.89
6.92
7.95
8.15
8.25
8.10
14.05
13.92
6.41
6.55
5.93
5.80
7.97
8.10
16 14
2
78
Yellow
74
Yellow
79
Yellow
70
Yellow
314.43
N O S
7a
H
12.66
12.47
12.27
12.35
13.91
14.10
13.14
12.95
11.47
11.62
11.33
11.28
10.40
10.57
9.68
24 18
4 3
442.50
H N O S
7b
145-47
AcOH
190-92
AcOH
204-206
AcOH
172-74
AcOH
226-28
AcOH
261-63
DMF
25 20
4 3
456.52
H N O S
7c
29 21
5 2
503.58
H N O S
7d
24 18
4 2
74
Orange
78
426.50
H N O S
7e
29 20
4 2
488.57
C H N O S
27 18
7f
Pale brown
4 2 2
75
494.59
C H N O S
33 22
7g
Reddish brown
4 2
73
538.63
H N O S
7h
>300
DMF
Reddish brown
C
C
C
C
C
C
C
35 22
4 3
71
Yellow
78
Yellow
73
Yellow
76
Yellow
72
Yellow
75
Yellow
74
Yellow
69
Brown
74
Brown
78
Orange
71
Yellow
74
Pale yellow
68
Pale yellow
70
Pale yellow
67
Pale yellow
61
Pale yellow
70
578.65
N OS
9.82
10.13
9.85
7.94
7.78
11a
11b
12a
12b
12c
12d
12e
12f
12g
12h
14
215-17
Dioxan
222-24
Dioxan
214-15
AcOH
254-56
AcOH
212-15
AcOH
214-15
AcOH
262-65
AcOH
220-23
AcOH
212-14
AcOH
222-25
AcOH
207-208
AcOH
190-92
EtOH
H
13 14
2
2
276.38
N OS
H
19 16
2
2
352.47
N O S
H
13.39
13.57
15.04
14.82
13.92
14.12
14.42
14.21
12.27
12.40
11.19
11.00
10.36
10.50
13.92
13.82
5.27
5.41
7.06
7.12
6.82
6.90
9.18
9.21
7.36
22 18
4 3
418.48
H N O S
26 19
5 2
465.54
H N O S
21 18
4 2
402.47
H N O S
26 16
4 2
388.45
C H N O S
24 16
4 2 2
456.55
C H N O S
30 20
4 2
500.58
H N O S
C
C
32 20
4 3
540.61
H N O S
22 18
4 2
402.48
C
H
NO
17 15
2
265.31
17a
17b
17c
17d
17e
17f
17g
17h
19a
19b
19c
C
H
N O
24 16
2
4
4
3
3
3
396.40
N O
135-36
EtOH
217-18
EtOH
188-90
EtOH
174-76
EtOH
C
C
C
C
H
25 18
2
410.43
N O
H
29 19
3
457.49
N O
H
24 16
2
380.40
N O
7.24
6.33
6.15
6.24
6.40
5.68
5.80
5.26
H
29 18
2
442.47
N O S
205-207
EtOH
Pale brown
59
Yellowish brown
70
Brown
61
Pale yellow
57
C
H
7.14
7.10
27 16
2 3
448.50
N O
192-94
AcOH
240-42
AcOH
>300
AcOH
218-20
AcOH
250-52
AcOH
C
H
33 20
2
3
4
2
492.53
N O
C
C
H
35 20
2
532.55
N O
5.30
H
14.80
14.50
14.88
14.71
12.77
12.57
23 14
4
378.39
C H N O
24 16
Yellow
63
Yellow
68
4
376.42
C H N O
29 18
4
438.49

May-Jun 2005
Reactions with Hydrazonoyl Halides 43
531
Table 1 (Continued)
Comp.
No.
Mp.,°C
Solvent
Color
Yield %
Mol. Formula Calcd./Found %
Mol.Wt.
C
H
N
S
19d
244-46
AcOH
250-52
AcOH
>300
DMF
242-5
EtOH
220-22
AcOH
188-90
AcOH
204-206
AcOH
245-47
AcOH
281-83
AcOH
291-93
AcOH
> 300
Orange
70
Orange
62
C
C
H
N O
72.95
73.10
81.13
81.00
79.53
79.35
71.51
71.43
72.13
72.00
68.03
67.91
70.37
70.10
70.37
70.45
68.03
68.11
70.37
70.40
70.37
70.25
68.28
68.40
68.46
68.60
74.22
74.10
74.54
74.52
72.22
72.10
69.30
69.45
74.53
74.50
74.84
74.92
72.51
72.43
69.57
69.75
3.62
3.43
4.12
4.23
3.18
3.08
3.33
3.12
3.82
4.05
4.15
4.20
3.93
4.10
3.25
3.40
4.15
4.00
3.93
4.20
3.25
3.10
3.00
2.89
3.28
3.14
3.94
4.20
4.24
4.10
4.11
4.10
3.49
3.20
3.54
3.45
3.85
3.90
3.73
3.90
3.11
3.00
12.60
12.58
11.46
11.58
10.59
10.45
9.27
9.10
8.85
8.75
7.21
7.40
7.82
7.90
12.31
12.10
7.21
7.30
7.82
8.00
12.31
12.40
11.38
11.10
15.21
14.94
8.66
8.75
8.41
8.34
8.15
8.20
8.08
8.12
8.69
8.57
8.45
8.52
8.18
8.10
8.11
7.21
7.35
27 16
4
444.51
N O
19e
19f
20
H
33 20
4
488.55
C H N O
35 20
Reddish Orange
59
4 2
528.57
N OS
Brown
61
Brown
58
Brown
50
Brown
51
Brown
40
Brown
51
Brown
49
Brown
41
Pale brown
47
Pale brown
44
Yellow
64
Yellow
61
Yellow
58
Yellow
49
Yellow
61
Yellow
57
C
C
H
10.60
10.42
10.13
10.25
8.25
8.12
8.95
9.20
9.39
9.31
8.25
8.10
8.95
9.20
9.39
9.50
8.68
8.80
8.70
8.92
18 10
2
302.36
N OS
21
H
19 12
2
316.38
H N O S
388.45
H N O S
22a
22b
22c
23a
23b
23c
24a
24b
26a
26b
26c
26d
27a
27b
27c
27d
C
C
22 16
2 3
21 14
2 2
358.42
C H N OS
20 11
3
341.39
H N O S
388.45
H N O S
C
C
22 16
2 3
21 14
2 2
358.42
C H N OS
20 11
341.39
C H N O S
21 11
369.40
C H N OS
21 12
3
DMF
> 300
DMF
> 300
3 2
4
DMF
368.42
N O
288-90
AcOH
284-86
AcOH
280-81
AcOH
302-304
AcOH
266-68
DMF
282-84
DMF
282-84
DMF
>300
DMF
C
C
C
H
30 19
3
4
4
5
485.50
N O
H
31 21
3
499.53
N O
H
31 21
3
515.53
C H Cl N O
30 18
3 4
519.94
N O
C
C
C
H
30 17
3
4
4
5
483.48
N O
H
31 19
3
497.51
N O
Yellow
54
Yellow
46
H
31 19
3
513.51
C H Cl N O
30 16
3 4
517.93
8.20
Table 2
1
H NMR Spectra of some Newly Synthesized Compounds
1
Compound
No.
H NMR (δ ppm)
7a
7c
7d
2.54 (s, 3H), 3.78 (s, 3H), 7.26-8.16 (m, 12H).
2.54 (s, 3H), 7.26-8.16 (m, 17H), 8.45 (s, br., 1H).
2.54(s, 3H), 2.65 (s, 3H), 7.26-8.20 (m, 12H).
12a
12c
12g
17b
17d
19b
19c
22b
23b
26b
26c
26d
27a
1.40 (t, 3H), 4.45 (q, 2H), 7.26-7.97 (m, 11H), 9.42 (s, 1H), 12.25 (s, br., 1H)
2.58 (s, 3H), 7.19-8.10 (m, 11H), 9.41 (s, 1H), 12.21 (s, 1H).
7.18-9.22 (m, 18H), 11.04 (s, 1H), 13.35 (s, 1H).
1.13 (t, 3H), 4.23 (q, 2H), 7.45-8.21 (m, 12H), 8.57 (s, 1H).
2.75 (s, 3H), 7.41-8.15 (m, 12H), 8.45 (s, 1H).
2.99 (s, 3H), 7.50-8.27 (m, 12H), 9.01 (s, 1H).
7.09-8.22 (m, 16H), 8.28 (s, 1H), 9.03 (s, 1H).
2.42 (s, 3H), 4.04 (s, 2H), 7.45-8.28 (m, 9H), 9.13 (s, 1H).
2.49 (s, 3H), 6.65 (s, br., 2H), 7.45-8.28 (m, 9H).
2.39 (s, 3H), 5.36 (d, 1H), 5.56 (d, 1H), 6.91-7.99 (m, 14H), 8.19 (d, 1H), 8.520 (d, 1H).
3.79 (s, 3H), 5.34 (d, 1H), 5.50 (d, 1H), 7.17-7.98 (m, 14H), 8.24 (d, 1H), 8.52 (d, 1H),
5.24 (d, 1H), 5.82 (d, 1H), 7.39-8.08 (m, 14H), 8.52 (d, 1H), 8.76 (s, 1H).
7.11-7.98 (m, 14H), 8.26 (d, 1H), 8.84 (d, 2H).

532
A. O. Abdelhamid and M. A. M. Alkhodshi
Vol. 42
resulting solid was collected and crystallized to give 3, 11a and
11b, respectively (Tables 1 and 2).
Synthesis of 5-Substituted 2-Naphtho[1,2-d]furan-2-ylethyli-
dene-3-phenyl-1,3,4-thiadiazoles 7a-h and 5-Substituted 3-Aryl-
2-(hydroxynaphthaline-1-ylmethylenehydrazino)-2,3-dihydro-
1,3,4-thiadiazoles 12a-h.
General Method.
Triethylamine (0.5 g (0.75 mL), 5 mmole) was added dropwise
with stirring to a mixture of the appropriate methyl carbod-
ithioate 3, 11a and 11b and the appropriate hydrazonoyl halides
4b-i (5 mmoles) in ethanol (20 ml). The resulting solid, which
formed after 30 min, was collected and crystallized from acetic
acid to give 2,3-dihydrothiadiazoles 7a-h and 12a-h in a good
yield (Tables 1and 2).
Synthesis of 3-(Dimethylamino)-1-naphtho[1,2-d]furan-2-
ylprop-2-en-1-one (14).
Equimolar a mounts of 1-naphtho[1,2-d]furan-2-ylethan-1-one
(1) and dimethylformamide-dimethylacetal (50 mmoles, each)
were refluxed in dry xylene (40 ml) for 4 h. The half of solution
was evaporated and then cooled. The resulting solid was col-
lected and crystallized to give 14 (Tables 1 and 2).
signals at δ = 5.36 (d, 1H), 5.53 (d, 1H) and 7.04-8.25
(m, 17H, ArH).
Compound 26a-d were oxidized in a reaction with p-
chloranil in boiling xylene to give 5-aryl-3-(naphtha[1,2-
d]furan-2-ylcarbonyl)-1-phenylpyrrolo[3,4-d]pyrazole-
4,6-diones 27a-d, respectively (Scheme 5). Structure of 27
was elucidated by elemental analysis and spectral data.
Thus, IR spectrum of 27c revealed bands at 1789, 1718,
Synthesis of 3-Substituted 4-(Naphtho[1,2-d]furan-2-ylcar-
bonyl)-4-phenyl-pyrazoles 17a-h.
General Method.
Equimolar a mounts of each 14 and the appropriate hydrazonoyl
halides 4a-h (5 mmoles) were refluxed in dry toluene (20 ml) con-
taining triethylamine (0.5 g (0.75 ml), 5 mmoles) for 3 h. The hot
solution was filtered and the filtrate was evaporated and triturated
with petroleum ether (40-60 °C). The resulting solid was collected
and crystallized to give 17a-h, respectively (Tables 1 and 2).
1
1668 (CO's) and 1621 (C=N). Its H NMR spectrum
showed signals at 3.75 (s, 3H), 6.98 (d, 2H), 7.52-8.17 (m,
11H), 8.58 (d, 1H), 8.90, (s, 1H), and 9.25 (s, 1H). MS
spectrum of 27d showed m/z = 471 (20%), 366 (25%), 365
(100%), 195 (29.8%), 139 (74.2%), 77 (33.9%). MS spec-
trum of 27d showed m/z = 519 (20%), 517 (47.3%), 278
(41%), 280 (13.8%), 195 (70%), 169 (22%), 139 (100%),
77 (79%).
Synthesis of 7-Substituted 4-Naphtho[1,2-d]furan-2-yl-2-phenyl-
6-hydropyrazolo[3,4-d]pyridazines 19a-f.
General Method.
An equimolar amount of each of the appropriate pyrazoles
17a-h (5 mmoles) and hydrazine hydrate (1 ml, 99%) in ethanol
(20 ml) was boiled under reflux for 2 h. The resulting solid was
collected and crystallized to give pyrazolo[3,4-d]pyridazines
19a-f, respectively (Tables 1 and 2).
EXPERIMENTAL
All melting points were determined on an electrothermal appa-
ratus and are uncorrected. IR spectra were recorded (KBr discs)
on a Shimadzu FT-IR 8201 PC spectrophotometer. H NMR
Synthesis of 6-Naphtho[1,2-d]furan-2-yl-2-sulfanylpyridine-3-
carbonitrile (20).
1
spectra were recorded in CDCl and (CD ) SO solutions on a
Method A.
3
3 2
Varian Gemini 300 MHz spectrometer and chemical shifts are
expressed in δ units using TMS as an internal reference.
Elemental analyses were carried out at the Microanalytical
Center of the Cairo University. Hydrazonoyl halides were
obtained as previously reported [23-29].
A mixture of compound 14 (2.65 g, 10 mmoles) and cyanoth-
ioacetamide (1 g, 10 mmoles) was refluxed in pyridine (25 ml)
for 5 hs, then poured onto ice-cold water and neutralized with
10% hydrochloric acid. The resulting solid was collected and
crystallized from ethanol to give 20 (Tables 1 and 2).
Synthesis of Methyl N'-(Naphtho[1,2-d]furan-2-ylethylidine)-
hydrazine-carbodithioate (3) and Alkyl N'-(2-Hydroxy-
naphthalin-1-ylmethylene)-hydrazinecarbodithioates 11a,b.
Method B.
A mixture of compound 14 (2.65 g, 10 mmole), cyanothioac-
etamide (1 g, 10 mmoles) and piperidine (0.5 ml) was refluxed in
ethanol (20 ml) for 3 h, then poured onto ice-cold water and neu-
tralized with hydrochloric acid (3 drops). The resulting solid was
collected and crystallized from ethanol to product identical in all
respects (mp., mixed mp. and spectra) with sample obtained in
method A.
General Method.
Equimolar a mounts of each 1-naphtho[1,2-d]furan-2-ylethan-
1-one (1) or 2-hydroxynaphthalene-1-carboxyaldehyde and the
appropriate alkyl hydrazinocarbodithioate (5 mmoles) in
2-propanol (20 ml) was stirred at room temperature for 2 h. The

May-Jun 2005
Reactions with Hydrazonoyl Halides 43
533
Synthesis of 2-Methylthio-6-naphtho[1,2-d]furan-2-ylpyridine-
3-carbonitrile (21).
was collected and crystallized from acetic acid to give 27a-d,
respectively (Tables 1 and 2).
A mixture of 20 (1.5 g, 5 mmoles) and potassium hydroxide
(0.28 g, 5 mmoles) in N,N-dimethylformamide (15 ml) was
stirred at room temperature for 6 h. Iodomethane (0.71 g, 5
mmoles) was added to the above solution while stirring. The
resulting solid was collected and crystallized to afford 21 (Tables
1 and 2).
REFERENCES AND NOTES
[1] Part 42: A. O. Abdelhamid, M. A. M. Alkhodshi, Sulfur,
Silicon and Relat. Elemn., 180, 149 (2005).
[2] A. Padwa, Angew. Chem. Int. Ed. Engl., 15, 123 (1976).
[3] R. Huisgen, R. Sustmann and G. Wallbillich, Chem. Ber.,
100, 1786 (1976).
Synthesis of Thieno[2,3-b]pyridines 23a-c.
[4] A. O. Abdelhamid and F. A. Attaby, J. Heterocyclic Chem.,
28, 41 (1991).
A mixture of 20 (1.5 g, 5 mmoles) and potassium hydroxide
(0.28 g, 5 mmoles) in N,N-dimethylformamide (15 ml) was
stirred at room temperature for 6 h. An appropriate quantity of
ethyl chloroacetate, chloroacetone, or chloroacetonitrile, (5
mmoles) was added to above solution while stirring. The reaction
mixture was stirred for 3 h; the resulting solid was collected and
crystallized to afford 22a-c, respectively (Tables 1 and 2). An
appropriate quantity of 22a-c (0.5 g) was refluxed in ethanol (15
ml) containing piperidine (3 drops) under reflux for 2 h. The solid
formed while boiling was collected and crystallized to give 23a-
c, respectively (Tables 1 and 2).
[5] D. I. Kornis, Comperhensive Heterocyclic Chemistry, Eds. A.
R. Katritzky, C. W. Rees, E.F.V. Scriven, Pergamon, (1996), Vol. 4.
[6] W. E. Kirkpatrick, T. Okabe, J. W. Hillyard, R. K. Robins, A.
I. Dren and T. Kovenison, J. Med. Chem., 20, 386 (1977).
[7] M. H. Elnagdi, Tetrahedron, 30, 2791 (1974).
[8] A. J. Ryan, P. G. Welling and S. E. Wright, Food Cosmet
Toxicol, 7, 287 (1970).
[9] A. Ebnother, E. Jucker and A. Lindeman, Helv. Chim. Acta,
42, 1201 (1959).
nd
[10] A. Burger, Medicinal Chemistry, 2 ed. Interscience, New
York, P. 345 (1945).
[11] E. Kanz, T. Hoffineistered and W. Woltke, Ger. Patent; 2131
790 (1971); Chem. Abstr., 78, 97694 (1973).
[12] B. W. Doming, U.S. Patent, 3 833 582 (1974); Chem. Abstr.,
81, 152270 (1974).
Synthesis of 7-Naphtho[1,2-d]furan-2-yl-3-hydropyrimidino-
[4',5':4,5]thieno[2,3-b]pyridine-4-one (24a) and 7-Naphtho[1,2-d]-
furan-2-yl-3-hydropyrimidino-[4',5':4,5]thieno[2,3-b]pyridine-4-
ylamine (24b).
[13] S. K. Mallick, A. R. Martin and R. G. Lingard, J. Med. Chem.,
14, 528 (1971).
[14] K. Vera, Collect. Czech. Chem. Commun., 58, 1195 (1993).
[15] A. O. Abdelhamid, M. M. M. Sallam and S. A. Amer,
Heteroatom Chem, 12, 468 (2001).
A mixture of 23c (1.7 g, 5 mmoles) and formic acid (99%) or
formamide (5 ml) in N,N-dimethylformamide (10 ml) was
refluxed for 5 h. The reaction mixture was poured onto crushed
ice (20 g). The resulting solid was collected and crystallized to
give 24a and 24b (Tables 1 and 2).
[16] A. O. Abdelhamid, H. F. Zohdi and N. A. Ali, Molecules, 5,
961 (2001).
Synthesis of 5-Aryl-3-naphtho[1,2-d]furan-2-ylcarbonyl)-1-
phenyl-3a,6a-dihydro-1H-pyrrolidino[4,3-d]pyrazole-4,6-diones
26a-d.
[17] A. O. Abdelhamid, N. M. Rateb and K. M. Dawood,
Phosphorus, Sulfur, Silicon and Relat Elemn., 167, 251 (2000).
[18] H. F. Zohdi, N. M. Rateb, M. M. M. Sallam and A. O.
Abdelhamid, J.Chem. Res., (S) 742; (M) 3329 (1998).
[19] A. O. Abdelhamid, S. M. Abdelgawad and S. F. El-Shrarnoby,
Phosphorus, Sulfur, Silicon and Relat. Elemn, 177, 2699 (2002).
[20] C. S. Pak, I. K. Youn and Y. S. Lee, Synthesis, 969 (1982).
[21] N. E. Searle, U.S. Patent, 2 444 536 (1984); Chem. Abstr., 42,
7340 (1948).
General Method.
Equimolar amounts of hydrazonoyl bromide 4h and appropri-
ate N-arylmalemide 25a-d (5 mmoles) were refluxed in dry
toluene (25 ml) containing triethylamine for 3 h. The hot solu-
tion was filtered and the filtrate was evaporated and triturated
with petroleum ether (40-60 °C). The resulting solid was col-
lected and crystallized from acetic acid to give 26a-d, respec-
tively (Tables 1 and 2).
[22] L. J. Bellamy, The Infrared Spectra of Complex Molecules
Ed., John Wiley, N.Y., London, (1975), p 150.
rd.
3
[23] G. Fravel, Bull. Soc. Chim. Fr., 31, 150 (1904).
[24] N. F. Eweiss and A. Osman, Tetrahedron Lett., 1169 (1979).
[25] A. S. Shawali and A. O. Abdelhamid, Bull. Chem. Soc. Jpn.,
Synthesis of 5-Aryl-3-(naphtha[1,2-d]furan-2-ylcarbonyl)-1-
phenylpyrrolo[4,3-d]pyrazole-4,6-diones 27a-d.
49, 321 (1976).
[26] A. S. Shawali and A. Osman, Tetrahedron, 27, 2517 (1971).
General Method.
[27] A. O. Abdelhamid and F. H. H. El-Shiatey, Phosphorus,
Sulfur, Silicon and Relat. Elemn., 39, 45 (1988).
[28] H. M. Hassaneen, A. S. Shawali, N. M. Elwan and N. M.
Abounada, Sulfur Letters, 14, 41 (1972).
[29] R. H. Wiley and G. H. Garboe, J. Am. Chem. Soc., 78, 624
(1956).
Equimolar amounts of the appropriate 26a-d and p-chloranil (5
mmoles each) in xylene (25 ml) was refluxed for 48 h. The reac-
tion mixture was cooled, washed with sodium hydroxide (0.1 N,
50 ml x 3) and then with water. The solution was evaporated and
triturated with petroleum ether (40-60 °C). The resulting solid