Reactions of Cyanothioacetamide Derivatives with 2-Hydrazinothiazol-4(5H)-one: Synthesis, Cyclization and Biological Evaluation of Several New Annelated Pyran, Thiazole, 1,2,4-Triazole and 1,2,4-Triazine Derivatives

Article abstract of DOI:10.1515/znb-1999-1218

The thiocarboxamidocinnamonitriles (2) reacted with 2-hydrazinothiazol-4(5H)-one (3) to afford the corresponding pyrano[2,3-d]thiazoles (6). Compounds 6 were used for the synthesis of several new annelated pyran, thiazole, 1,2,4-triazole and 1,2,4-triazine derivatives via their reactions with chloroacetic acid, ethyl chloroformate, diethyl oxalate and acetylacetone. Structures were established based on elemental and spectral data studies. Some of the newly synthesized heterocyclic derivatives were tested for their antimicrobial activity.

Full text of DOI:10.1515/znb-1999-1218

Reactions of Cyanothioacetamide Derivatives with 2-Hydrazinothiazol-4(5//)-one:
Synthesis, Cyclization and Biological Evaluation of Several New Annelated Pyran,
Thiazole, 1,2,4-Triazole and 1,2,4-Triazine Derivatives
Sanaa M. Eldin
Department of Pesticidal Chemistry, National Research Center, Dokki, Giza, A. R. Egypt.
E-mail: Fawzy@chem-sci.cairo.eun.eg
Z. Naturforsch. 54b, 1589-1597 (1999); received July 2, 1999
Thiocaboxamidocinnamonitriles, Pyrans, Thiazoles, 1,2,4-Triazoles, 1,2,4-Triazines
The thiocarboxamidocinnamonitriles (2) reacted with 2-hydrazinothiazol-4(5//)-one (3) to
afford the corresponding pyrano[2,3-d]thiazoles (6). Compounds 6 were used for the synthe-
sis of several new annelated pyran, thiazole, 1,2,4-triazole and 1,2,4-triazine derivatives via
their reactions with chloroacetic acid, ethyl chloroformate, diethyl oxalate and acetylacetone.
Structures were established based on elemental and spectral data studies. Some of the newly
synthesized heterocyclic derivatives were tested for their antimicrobial activity.
Introduction
this reaction product gave m /z-363. Based on the
above data this product could be formulated as the
5-oxopyrano[2,3-6?]thiazole 6a.
Cyanothioacetamide (1) and its ylidene deriva-
tives (2 ) are versatile reagents and their utility in
heterocyclic synthesis has recently gained a con-
siderable attention in this laboratory [1-8]. Dur-
ing the up-dating of the review [9] dealing with
the chemistry of 1 and 2 it has been observed that
nothing has been reported on their reactions with
2-hydrazinothiazol-4(5//)-one (3). It was thus de-
cided to investigate this reaction and to shed more
light on the synthetic potential of 1-3. These reac-
tions resulted in the synthesis of, otherwise diffi-
cult obtainable, annelated pyrans, thiazoles, 1,2,4-
triazoles and 1 ,2,4-triazines of which some deriva-
tives were tested for their antimicrobial activity.
The formation of 6a in this reaction is assumed
to proceed via initial formation of the intermedi-
ate Michael adduct 4 which is then cyclized via
addition to the nitrile function to give the imino-
pyrano[2,3-d]thiazole derivatives 5. Compound 5
is then autoxidized and hydrolyzed under the ap-
plied reaction conditions to give the isolable final
product 6a rather than tautomerization to give 7
(Scheme 1).
Analogously, the thiocarboxamidocinnamonitrile
derivative 2b reacted with 3 to yield 6b whose iden-
tity was established also on the basis of elemental
and spectral data as for 6a (cf. Experimental Part).
Compounds 6a,b were taken as the starting ma-
terials for the present study and their synthetic po-
tential was demonstrated by their reactions with
a variety of chloroacids, chloroesters, diesters and
Results and Discussion
A
reaction product of molecular formula
Q 3H9N5S2O4 was obtained on reacting the thio-
carboxamidocinnamonitrile derivative 2a with 2 - diketones. Thus, it has been found that 6a reacted
hydrazinothiazol-4(5//)-one (3) in absolute etha- via its thiocarboxamido group with chloroacetic
nol containing a catalytic amount of triethylamine. acid in glacial acetic acid to give a product of mo-
The IR spectrum of this product showed the ab-
sence of the absorption bands of the nitrile func-
lecular formula Q 5H9N5S2O5. No band for thioa-
midic C=S group was detected in its IR spectrum
tion and a band of ring-CO group was detected. while an additional ring-CO group was clearly
Its 'H NMR spectrum revealed the presence of shown. Its 'H NMR spectrum revealed the pres-
signals of NH, NH2 and aromatic protons only. No
signals in the region of d = 4 -6 ppm were detected
ence of NH, aromatic and thiazole-CH2 protons.
In the light of the above findings this reaction pro-
which, if present, may be attributed to pyran 3-H duct was formulated as the 5-oxopyrano[2,3-d]thi-
or 4-H protons. Moreover, the mass spectrum of
azole (8a).
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S. M. Eldin ■Reactions of Cyanothioacetamide Derivatives
s
studies (cf. Experimental Part). The structure of
each of 8 a,b was further established via their reac-
tions with the appropriate aromatic aldehydes in
different media. Thus, 8 a reacted with /?-nitroben-
zaldehyde and 8b reacted with anisaldehyde in
boiling ethanol to give the corresponding 7-aryl-2-
arylhydrazono-6-(2'-thiazolidin-4'-on-2'-yl)-5-
l
/ CN
CH.-C-NH,
Ar-CH = C
^CSNHj
2a,b
EtOH
TEA
XX
oxopyrano[2,3-öf]thiazole
derivatives
(9a,b),
respectively. The 'H NMR spectra of 9a,b revealed
the presence of the two protons of the two Ar-
CH = moieties at d = 8.2 and 8.58 ppm. When per-
forming the above reaction in boiling glacial acetic
acid the corresponding 6-oxopyrano[2\3':4,5]thia-
zolo[2,3-c]l,2,4-triazole derivatives 10a,b were ob-
tained. The ’H NMR spectra of 10a,b revealed
only the presence of one Ar-CH = proton in addi-
tion to aromatic protons in each case, this indi-
(-N H 3)
(-2H)
cated that the arylhydrazono group at position
2
in each of 9a,b was involved in the cyclization step
leading to 10a,b. Moreover, a solid evidence for
structure 1 0 a,b came from their authentication via
reacting 8 a,b with the appropriate aromatic alde-
hyde in boiling glacial acetic acid. Compounds
1 0 a,b prepared by either of the two routes were
found completely identical in their characteriza-
tion and spectral data (cf. Scheme 2).
6a,b
a, Ar=C6H4-NOr
p
b, Ar=C6H„-OCH3-p
6a,b
8a, b
ArCHO/ EtOH
ArCHO/AcOH
In a similar manner, 6b reacted with chloroace-
An interesting course of condensation and cycli-
tic acid to yield 8b whose constitution was also zation reactions with 6a,b was also investigated,
established based on elemental and spectral data Thus, 6a,b condensed with the appropriate aro-
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1591
S. M. Eldin • Reactions of Cyanothioacetamide Derivatives
matic aldehyde in ethanol to yield the correspond- tives (13a,b) respectively via cyclization using boil-
ing 7-aryl-2-arylhdrazono-6-thio-carboxamido-5- ing glacial acetic acid. On the other hand, the
oxopyrano[2,3-d]thiazole derivatives 11a,b respec- constitution of 13a,b was further elucidated, in ad-
tively. IR and
NMR spectra of 11a,b seemed to
dition to elemental and spectral data, via their au-
be of no great help in establishing their structure. thentication using two other different routes as
Accordingly, 11a,b were authenticated via reacting follows:
3 with the appropriate aromatic aldehyde to give
a- Conduction of the reaction of 6 a,b with the
the corresponding bis(arylidene) derivatives 1 2 a,b. appropriate aromatic aldehydes in boiling glacial
Compounds 12a,b were then reacted with cya-
nothioacetamide (1 ) to yield the corresponding
1 1 a,b with the same characterization data as those
acetic acid.
b- Cyclization of each of 12a,b via boiling their
solutions in glacial acetic acid to give the corre-
obtained via the first route (cf. Scheme 3). A fur- sponding thiazolo[2,3-c]pyrazole derivatives 14a,b
ther support for the constitution of 1 1 a,b came respectively whose structure was, in turn, estab-
from their conversion into the corresponding py- lished based on elemental and spectral data
rano[2',3':4,5]-thiazolo[2,3-c]l,2,4-triazole deriva- studies. Compounds 14a,b were then reacted with
ArCHO
6a,b
EtOH
HjNSC
NHN=CH-Ar
12a, b
13a,b
ArCHO
CICH,COOH
11a,b
10a,b-
Scheme 3
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1592
S. M. Eldin ■Reactions of Cyanothioacetamide Derivatives
cyanothioacetamide (1) in ethanol to yield 13a,b
respectively. (cf. Scheme 3).
Compounds 13a,b reacted with chloroacetic acid
to give the corresponding 7-thiazolonylpyra-
Accordingly, this reaction product could be for-
mulated as 8-(/?-nitrophenyl)-3,6-dioxo-7-thiocar-
boxamidopyrano[2\3' :4,5]thiazolo[2,3-c] 1,2,4-
triazole 18a. Compound 18a then reacted with
no[2\3':4.5]thiazolo[2,3-c] 1,2,4-triazole derivatives chloroacetic acid to yield the 6-oxo-7(2'-thiazolin-
4'-on-2'-yl)-pyrano[2',3':4,5]thiazolo[2,3-c]-l,2,4-
15a,b respectively. The 'H NMR spectra of 15a,b
revealed the presence of signals of thiazolonyl- triazole 19a whose constitution was, in turn, estab-
CH2 and aromatic protons only. Their mass lished based on elemental and spectral data {cf.
spectra gave the exact molecular mass in each Experimental Part). Moreover, 19a could be au-
thenticated via reaction of 8a with ethyl chloro-
came from their authentication by first reaction of formate in ethanol.
case. A further proof for the constitution of 15a,b
Analogously, 6b reacted with the same ester to
yield 18b, which reacted also with chloroacetic
11a,b with chloroacetic acid in ethanol to give the
corresponding 6-thiazolonylpyrano[2,3-d]thiazole
derivatives 16a,b. Compounds 16a,b were, in turn, acid to produce 19b. Compound 19b was also inde-
cyclized via boiling their solutions in glacial acetic pendently synthesized via the reaction of 8b with
acid to furnish 15a,b respectively. On the other ethyl chloroformate (cf. Scheme 4).
hand, treatment of 15a,b with the appropriate aro-
matic aldehydes led to the formation of the corre-
sponding 10a,b mentioned before (cf Scheme 3).
In continuation of this work, each of 6a,b re-
acted with diethyl oxalate in ethanol to give the
corresponding 9-aryl-8-thiocarboxamido-3,4,7-tri-
The behaviour of 6a,b towards the action of oxopyrano[2',3':4,5]thiazolo[2,3-c] 1,2,4-triazine
derivatives 20a,b respectively.
ethyl chloroformate was also investigated. Thus, 6a
Structure of 20a,b was established based on ana-
reacted with ethyl chloroformate in absolute etha-
nol to give a reaction product with molecular for- lytical and spectral data studies. The thiocarboxa-
mido group in 20a,b was also involved in the reac-
tion with chloroacetic acid thus yielding the
corresponding thiazolonylpyranothiazolo-l,2,4-tri-
azine derivatives 21a,b respectively. The ]H NMR
spectra of 21a,b revealed the presence of thiazolo-
nyl-CH2, NH and aromatic protons only and
seemed to be of little help in establishing the struc-
mula C14H7N5S20 5 corresponding to equimolecu-
lar addition of 6a to the ester followed by loss of
HC1 and ethanol. The IR spectrum of this product
showed the band of additional ring-CO group
more than those of the starting 6a. Its ]H NMR
spectrum revealed the signals of NH, NH2 and
aromatic protons only.
CIC02Et
19a,b
EtOH
18a,b
Scheme 4
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1593
S. M. Eldin - Reactions of Cyanothioacetamide Derivatives
6a,b
+ ÄCjCH,
6a,b
+ (C 02Et)2
H,NSC
20a,b
AcOH
CICHoCOOH
CICH,COOH MeOH
N^ \ ^ °
EtOH
8a,b
+ (C 02Et)2
21a,b
Scheme 5
Scheme 6
ture. Thus, 21a,b were authenticated by the reac-
tion of 8a,b with diethyl oxalate in ethanol (cf.
Scheme 5).
Experimental
All melting points are uncorrected. The IR
spectra in KBr discs were recorded on Perkin-El-
mer FT-IR type 4 and Pye Unicam SP-1100 spec-
trophotometers. The 'H NMR spectra were re-
corded on Varian EM 390-90 MHz,Varian
Gemini 200 and Brücker WP-80 spectrometers
using CDC13, DMSO-d6 and (CD3)2CO as solvents
and TMS as an internal standard. Chemical shifts
are expressed as d ppm. Mass spectra were re-
corded on Hewlett-Packard GC-MS type 2988
series A using DIP technique at 70 eV. Micro-
analyses were performed at the Microanalytical
Center of Cairo University using Perkin-Elmer
2400 CHN Elemental Analyzer.
Finally, 6 a,b reacted with acetylacetone in meth-
anol to give the corresponding 2-(2',4'-dimethylp-
yrazol-l'-yl)-5-oxo-6-thiocarboxamidopyrano[2,3-
djthiazole derivatives 22a,b whose 'H NMR
spectra revealed the presence of NH2, pyrazole-
CH3, pyrazole H-4 and aromatic protons in their
proper positions. Compounds 22a,b reacted with
chloroacetic acid to yield the corresponding 2 '-di-
methylpyrazolyl-5-oxo-6-thiazolinonylpyrano[2,3-
d]thiazole derivatives 23a,b respectively. The
structure of 23a,b was established based on analyt-
ical and spectral data in addition to their indepen-
dent synthesis by the reaction of 8 a,b with acetyl-
acetone in methanol (cf. Scheme 6 ).
Compounds 1[11], 2[12] and 3[13] were pre-
pared according to literature procedures.
Reactions o f 1 with 2a,b, 12a,b and 14a,b
General procedure
Antimicrobial Activity
A solution of 1 (0.01 mole) in absolute ethanol
(30 ml) containing triethylamine (0.5 ml) was
treated with each of 2a,b, 12a,b and 14a,b (0.01
mole) and the whole was heated under reflux for
5 h. The solid products obtained after cooling were
filtered off and crystallized from the proper
solvent to give 6a,b; 11a,b and 13a,b respectively
(Tables I and II).
The preliminary antimicrobial evaluation of
some representative examples of the newly syn-
thesized heterocyclic derivatives against Gram+
G ram - bacteria, yeast and fungi compared with
NA using the cup-plate method [10] showed
strong activity of compounds 15b, 20b and 23b
against Bacillus subtilis and Staphylococcus
aureus. Compounds 9b and 18a showed a moder-
ate activity against Aspergillus niger while the rest
of the compounds showed only slight activity or
inactivity against the tested organisms (cf. Ta-
ble III).
Reactions with chloroacetic acid
General procedure
A solution of chloroacetic acetic acid (0.01
mole) in glacial acetic acid (25 ml) and 0.01 mole
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1594
S. M. Eldin • Reactions of Cyanothioacetamide Derivatives
Table I. Characterization data of the new compounds.
Comp.
colour
M.p. [°C]
solvent
Molecular
formula
Yield
[%]
%
Analysis Calcd/(Found)
c
H
N
S
6a
b r o w n
6b
252-3
E t O H
228
42.97
(43.1)
48.27
(48.5)
44.66
(44.7)
49.48
(49.6)
52.02
(52.3)
61.53
(61.7)
52.17
(52.4)
61.73
(61.9)
48.38
(48.6)
56.65
(56.8)
51.38
(51.1)
62.12
(61.9)
48.58
(48.3)
56.89
(57.1)
51.38
(51.5)
62.46
(62.7)
49.43
(49.3)
57.14
(57.4)
49.25
(49.1)
56.91
(57.2)
43.18
(43.4)
48.12
(48.4)
44.75
(44.9)
49.27
(49.4)
43.16
(43.4)
47.76
(47.6)
44.63
(44.7)
48.86
(48.6)
50.58
(50.8)
2.47
(2.6)
3.44
(3.6)
2.23
(2.4)
3.09
(3.2)
2.24
(2.4)
3.84
(4.0)
1.95
68
62
53
71
65
68
72
76
61
51
66
64
48
61
55
59
77
82
60
52
67
72
60
54
66
68
54
52
72
17.63
(17.4)
18.39
(18.6)
15.88
(15.6)
16.49
(16.7)
9.56
19.28
c
13h 9n 5s 2o 4
(19.4)
16.09
(16.2)
17.36
(17.2)
14.43
(14.3)
14.64
(14.8)
8.97
c
14h 12n 4S 2 0 3
y e llo w
E t O H
262-3
A c O H
242-4
AcOH
212-3
E t O H
206-7
E t O H
192
8a
c
15h 9n 5s 2o
16h 12n 4s 2o
5
o r a n g e
8b
c
4
y e llo w
9a
b r o w n
9b
c 29 h 15n 7s 2o
9
6
(9.8)
c
32h 24n 4s 2o
10.25
(10.4)
9.59
o r a n g e
(9.2)
10a
C29H 13N7S20 9
14.69
(14.9)
9.00
y e llo w
10b
E t O H
(2.2)
3.53
(3.7)
2.41
(9.8)
181
10.28
(10.4)
12.90
(13.1)
13.73
(14.0)
8.06
(8.3)
8.72
(9.0)
12.95
(13.2)
13.79
(14.0)
8.06
(8.3)
8.76
c
c
c
32h 22n 4s 2o
20h 12n 6s 2o
22h 18n 4s 2o
6
6
4
y e llo w
E t O H
183
(9.3)
11a
16.93
(17.2)
12.01
(12.3)
17.64
(17.8)
11.44
(11.6)
17.00
(17.3)
12.06
(12.3)
17.63
(17.8)
11.50
(11.3)
15.73
(15.8)
11.11
(11.2)
15.67
(15.8)
11.06
(11.3)
17.99
(18.2)
14.97
(15.1)
16.31
(16.6)
13.52
(13.3)
16.78
(16.6)
13.93
(13.8)
15.31
(15.2)
12.66
(12.8)
16.39
(16.6)
b r o w n
lib
E t O H
(2.7)
3.86
(4.0)
2.77
(2.5)
4.63
(4.5)
2.02
(2.2)
3.44
(3.6)
2.77
(3.0)
4.10
(4.3)
1.87
(2.1)
3.17
(3-4)
2.23
(2.4)
3.55
(3.7)
1.79
168
E t O H
132
b r o w n
12a
c
17h
„
n
5s
o
o
5
w h ite
12b
E t O H
118
E t O H
156
AcOH
162
AcOH
127
c
19h 17n 3s
3
w h ite
13a
c
20h 10n 6s 2o
22h 16n 4s 2o
6
b r o w n
13b
c
4
b r o w n
14a
c
17h
„
n
5s
o
o
5
y e llo w
14b
AcOH
103
c
19h 15n 3s
3
y e llo w
A c O H
(8.9)
15a
212
11.98
(12.2)
12.69
(12.8)
11.94
(12.2)
12.64
(12.8)
16.45
(16.6)
17.11
(17.4)
14.91
(15.2)
15.45
(15.2)
15.34
(15.2)
15.92
(16.2)
14.00
(13.8)
14.47
(14.7)
14.98
(15.2)
c
22h 10n 6s 2o 7
b r o w n
15b
E t O H
262-3
E t O H
187
C 24H ]f,N 4S 20
5
7
5
b r o w n
16a
c
c
22h 12n 6s 2o
24h 18n 4s 2o
14h 7n 5s 2o
o r a n g e
16b
E t O H
194
o r a n g e
E t O H
188
18a
c
5
y e llo w
18b
E t O H
(2.0)
2.67
(2.9)
1.63
(2.0)
2.41
162
ci^h k)n4s20 4
y e llo w
E t O H
248-9
AcOH
236-7
AcOH
217-8
E t O H
197
E t O H
272-3
E t O H
261-2
E t O H
287-8
E t O H
19a
c
16h 7n 5s 2o
17h 10n 4s 2o
15h 7n 5s 2o
6
b r o w n
19b
c
5
b r o w n
(2.6)
1.67
20a
c
6
y e llo w
20b
(1.9)
2.48
(2.6)
1.53
(1.8)
2.26
(2.5)
3.04
(3.3)
c
16h 10n 4s 2o
17h 7n 5s 2o
18h 10n 4s 2o
5
b r o w n
21a
c
7
y e llo w
21b
c
6
y e llo w
22a
y e llo w
cish 13n5s20 4
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1595
S. M. Eldin ■Reactions of Cyanothioacetamide Derivatives
Table I. (contiued).
Comp.
colour
M.p. [°C]
solvent
Yield
[%]
Molecular
formula
% Analysis Calcd/(Found)
C
H
N
S
22b
brown
23a
orange
23b
228-9
MeOH
248-9
EtOH
213-4
EtOH
68
52
48
55.33
(55.5)
51.39
(51.6)
55.75
(55.9)
3.88
(4.0)
2.78
(2.6)
3.53
(3.4)
13.59
(13.8)
14.98
(14.8)
12.38
(12.2)
15.53
(15.7)
13.70
(13.5)
14.15
(14.3)
ci9h 16n4s20 3
c 20h 13n 5s2o 5
c 2ih 16n 4s2o 4
orange
Table II. IR and 'H NMR data.
Comp.
6a
IR [KBr, cm"']
*H NMR [b ppm]
7.1-8.0 (m, 4H, A rH ’s), 9.7(s, br, 2H, NH,) and 10.2 (s, br.,
3H, NHNH2).
3.4 (s, 3H, ÖCH3); 12-1.9 (m, 4H, A rH ’s) and 9.8(s, br., 2H,
NH2) and 10.3(s, br, 3H, NHNH2).
5.6 (s, 2H, thiazolinone-CH?); 7.1-7.8 (m, 4H, A rH’s) and 10.0
(s, br., 3H, NHNH2).
3390, 3320, 3260 (NH and NH2);
1730 (ring-CO) and 1250(C=S).
3380. 3400, 3280 (NH and NH2);
1740 (ring-CO) and 1245(C=S).
3400, 3370, 3320 (NH and NH2);
2980 (sat. CH); 1730 (ring-CÖ)
and 1680 (thiazolinone-CO).
3390, 3350, 3300 (NH and NH2);
2980 (sat. CH); 1720 (ring-CÖ)
and 1680 (thiazolinone-CO).
3320 (NH); 1735 (ring-CO) and
1690 (thiazolinone-CO).
6b
8a
8b
3.2 (s, 3H, OCH3); 5.8 (s, 2H, thiazolinone-CH2); 7.1-8.8 (m.
4H, A rH’s) and 10.3 (s, br., 3H, NHNH2).
9a
7.0-7.9 (m. 12H, ArH’s); 8.2(s, 2H, two Ar-CH=) and 9.8 (s,
br., 1H, NH).
3.4 (s, 9H, three OCH,); 7.3-8.1 (m, 12H, A rH ’s); 8.5(s, 2H,
two Ar-CH=) and 10.1 (s, br., 1H, NH).
9b
3320 (NH); 1740 (ring-CO) and
1700 (thiazolinone-CO).
10a
10b
11a
11b
12a
12b
13b
1735 (ring-CO) and 1690
(thiazolinone-CO).
1740 (ring-CO) and 1700
(thiazolinone-CO).
3400, 3350, 3300 (NH and NH2);
1730 (ring-CO) and 1250 (C=S).
3390, 3350, 3300 (NH and NH2);
1740 (ring-CO) and 1255 (C=S).
3300 (NH) and 1700
(thiazolinone-CO).
3310 (NH) and 1690
(thiazolinone-CO).
3400, 3300 (NH2); 1730
(ring-CO) and 1250 (C=S).
1680 (thiazolinone-CO).
1685 (thiazolinone-CO).
3.2 (s, 9H, three OCH,); 7.0-7.8 (m, 12H, A rH ’s); and 8.4(s,
1H, Ar-CH=).
7.0-8.0 (m, 8H, A rH ’s); 8.3(s, 1H, Ar-CH=) and 9.8 (s, br., 3H,
NH and NH2).
3.2 (s, 6H, two OCH,); 7.1-7.9 (m, 8H, A rH ’s); 8.4(s, 1H, Ar-
CH=) and 9.8 (s, br., 3H, NH and NH,)-
7.0-7.9 (m, 8H, A rH ’s); 8.2(s, 2H, two Ar-CH=) and 9.8 (s, br..
1H, NH).
3.2 (s, 6H, two OCH3); 7.2-8.0 (m, 8H, A rH ’s) and 9.8 (s, br.,
2H, NH2).
14a
14b
3.3 (s, 6H, two OCH3); 7.2-8.0 (m, 8H, A rH ’s) and 8.5(s, 1H,
Ar-CH=).
2980 (sat. CH); 1735 (ring-CO)
and 1680 (thiazolinone-CO).
2980 (sat. CH); 1740 (ring-CO)
and 1690 (thiazolinone-CO).
2985 (sat. CH); 1740 (ring-CO)
and 1700 (thiazolinone-CO).
3290 (NH); 2980 (sat. CH); 1725
(ring-CO) and 1685
5.8 (s, 2H, thiazolinone-CH2) and 7.1-8.1 (m, 8H, ArH’s).
15a
15b
16a
16b
3.1 (s, 6H, two OCH3); 5.8 (s, 2H, thiazolinone-CH?) and 7.0-
7.9 (m, 8H, A rH ’s).
5.9 (s, 2H, thiazolinone-CH2); 7.1-8.1 (m, 8H, A rH’s); 8.2(s,
1H, Ar-CH=) and 9.8 (s, br.flH , NH).
3.3 (s, 6H, two OCH,); 5.9 (s, 2H, thiazolinone-CH2); 7.0-7.8
(m, 8H, ArH’s); 8.15(s, 1H, Ar-CH=) and 9.9 (s, br., 1H, NH).
(thiazolinone-CO).
18a
18b
3400, 3370, 3250 (NH and NH2);
1730 (ring-CO); 1710 (pyrazo-
lone-CO) and 1250 (C=S).
3390, 3350, 3150 (NH and NH2);
1740 (ring-CO); 1700 (pyrazo-
lone-CO) and 1255 (C=S).
7.0-7.8 (m, 4H, ArH’s) and 9.8 (s, br., 3H. NH and NH2).
3.4 (s, 3H, OCH3); 1.0-1.9 (m, 4H, A rH ’s) and 10.1 (s, br., 3H,
NH and NH2).
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1596
S. M. Eldin • Reactions of Cyanothioacetamide Derivatives
Table II. (continued).
Comp.
19a
IR |KBr, c m 1]
'H NMR {b ppm]
3300 (NH); 2980 (sat. CH); 1740
(ring-CO); 1710 (pyrazolone-
CO)i and 1680 (thiazolinoe-CO).
3310 (NH); 2985 (sat. CH); 1735
(ring-CO); 1700 (pyrazolone-
CO) and 1670 (thiazolinoe-CO).
3400. 3370, 3310 (NH and NH,);
1740 (ring-CO); 1700, 1680 (-
CO-CO-NH-) and 1250 (C=S).
3400, 3380, 3300 (NH and NH,);
1740 (ring-CO); 1700. 1680
(-CO-CO-NH-) and 1250 (C=S).
3310 (NH); 2980 (sat. CH); 1740
(ring-CO); 1700, 1690 (-CO-CO-
NH-) and 1250 (C=S).
3320 (NH); 2985 (sat. CH); 1730
(ring-CO); 1710, 1685 (-CO-CO-
NH-) and 1250 (C=S).
5.7 (s, 2H, thiazoline-CH,); 7.1-8.0 (m, 4H, ArH’s) and 10.3
(s, br., 1H. NH).
19b
20a
20b
21a
21b
7.2-8.0 (m, 4H, A rH’s) and 10.5 (s, br., 3H, NH and NH2).
5.8 (s, 2H, thiazoline-CH2); 7.0-7.8 (m. 4H, A rH’s) and 9.9 (s,
br., 1H, NH).
3.2 (s, 3H, OCH3); 5.7 (s, 2H, thiazoline-CH2); 7.0-7.8 (m, 4H,
A rH ’s) and 10.2 (s, br., 1H, NH).
22a
22b
1735 (ring-CO) and 1255 (C=S).
2.3 (s, 3H, pyrazolyl-CH3); 2.6 (s, 3H, pyrazolyl-CH3); 7.0-8.1
(m, 5H, ArH’s and pyrazolyl-CH) and 9.9 (s, br., 2H, NH2).
2.35 (s, 3H, pyrazolyl-CH3); 2.6 (s, 3H, pyrazolyl-CH3); 3.3 (s,
3H, OCH3); 7.1 -8.1 (m, 5H. ArH’s and pyrazolyl-CH) and 10.1
(s, br., 2H, NH2).
1740 (ring-CO) and 1260 (C=S).
23a
23b
2985 (sat., CH,) and 1260 (C=S).
2985 (sat., CH2) and 1260 (C=S).
2.3 (s, 3H, pyrazolyl-CH3); 2.5 (s, 3H, pyrazolyl-CH3); 3.3 (s,
3H, OCH3); 5.9 (s, 2H, thiazolinoe-CH2) and 7.0-8.Ö (m, 5H,
A rH ’s and pyrazolyl-CH).
of each of 6 a,b; 13a,b; 11a,b (in ethanol); 18a,b; and 12a,b then heated under reflux for 5 h. The
2 0 a,b and 2 2 a,b was heated under reflux for 5 -
reaction mixture was then cooled and poured onto
6 h. The solid products obtained on hot or after ice-cold water. The solid products obtained were
filtered off, washed with water then crystallized
proper solvent to give 8 a,b; 15a,b; 16a,b; 19a,b; from the proper solvent to give 10a,b; 13a,b; 13a,b
cooling were filtered off and crystallized from the
and 14a,b respectively (Tables I and II).
21a,b and 23a,b respectively (Tables I and II).
Reactions with aromatic aldehydes in ethanol
General procedure
Cyclization reactions in glacial acetic acid
General procedure
A solution of each of 9a,b or 16a,b (1 g) in gla-
cial acetic acid (20 ml) was heated under reflux for
3 h. The solid obtained after cooling was filtered
off and crystallized from the proper solvent to
yield 10a,b and 15a,b respectively (Tables I and
A solution of the appropiate aromatic aldehyde
(a = /?-nitrobenzaldehyde; b = p-anisaldehyde) in
ethanol (0.01 mole in 30 ml) was treated with 0.01
mole of each of 8 a,b; 15a,b; 6 a,b and 3 and then
heated under reflux for 5 h. The solid products ob-
tained after cooling were filtered off and crystall- II).
lized from the proper solvent to yield 9a,b; 10a,b;
11a,b and 12a,b respectively (Tables I and II).
Reactions o f 6 a,b and 8 a,b with each o f ethyl
chloroformate, diethyl oxalate and acetylacetone
Reactions with aromatic aldehydes in glacial
acetic acid
General procedure
A solution of each of 6 a,b (0.01 mole) in 20 ml
of ethanol (or methanol) was heated with 0 .0 1
mole of each of ethyl chloroformate, diethyl oxa-
late or acetylacetone and then heated under reflux
for 4 h. The solids obtained after cooling were fil-
General procedure
A solution of the appropriate aromatic aldehyde
(0.01 mole) in glacial acetic acid (30 ml) was
treated with 0 .0 1 mole of each of 8 a,b; 6 a,b; 1 1 a,b
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1597
S. M. Eldin • Reactions of Cyanothioacetamide Derivatives
Table III. Antimicrobial activity.
tered off and crystallized from the proper solvent
to yield 18a,b; 20a,b and 22a,b respectively
(Tables I and II).
The repetition of the same experiments using
8a,b instead of 6a,b afforded compounds 19a,b;
21a,b and 23a,b respectively (Tables I and II).
V
VI
Comp.
I
II
III
IV
_
6a
6b
8a
8b
9b
+
+
-
++
+
+
++
+
+
+
+
+
-
+
++
+
+
-
+
+
+
++
-
-
+
-
-
++
-
-
++
-
++
-
Acknowledgement
-
10a
10b
11a
14b
15a
15b
16b
18a
18b
19b
20b
21a
22a
23b
++
-
-
+
+
+
+
+
-
+
+
+
+
+
++
-
+++
++
+
+
+
+
-
+
+
-
Thanks are due to Prof. Dr. Y. E. Saleh. Botany
Department, Faculty of Science, Cairo University
for carrying out the biological activity of the newly
synthesized heterocyclic derivatives.
+
+
+
+++
++
+
++
+
+
+
+
+++
+
++
+
-
+
++
-
++
-
+
-
+++
++
+
+
+ +
-
-
+
-
+++
++
-
+++
+
++
-
+
++
+
-
-
+
-
++
+
++
+++
I
II
= Bacillus subtilis (Gr +ve)
= Staphylococcus aureus (Gr +ve)
III = Escherichia coli (Gr -ve)
IV = Pseudomonas aeruginosa (G -ve)
V
= Candida albicans (yeast)
VI = Aspergillus niger (fungus)
+++ = Highly active; Inhibition zone around the disk =
3 -4 mm.
++ = Fairly active; Inhibition zone around the disk =
2 mm.
+
= Slightly active; Inhibition zone around the
disk = 1 mm.
-
= Inactive; No inhibition zone around the disk.
[7] F. A. Attaby, S. M. Eldin. Z. Naturforsch. 54b, 788,
(1999).
[8] S. M. Eldin. Z. Naturforsch. 54b,674 (1999).
[9] B. Y. Riad, A. M. Negm, S. E. Abdou. H. A. Da-
boun. Heterocycles 26, 205 (1987).
[1] F. A. Attaby, S. M. Eldin, M. A. A. Elneairy, Het-
eroatom Chem. 9, 571 (1998).
[2] F. A. Attaby, S. M. Eldin, M. A. A. Elneairy, J.
Chem. Res. (5) 632, (M) 2754 (1998).
[3] F. A. Attaby, S. M. Eldin, W. M. Basyouni, M. A. A.
Elneairy, Phosphorous, Sulfur and Silicon 119, 1 [10] A. Abou-Zeid, Y. Sheata, J. Ind. Pharm. 31, 72
(1996).
(1969).
[4] S. M. Eldin, J. Chem. Res. (5) 730, (M) 3207 (1998).
[5] F. A. Attaby, S. M. Eldin, J. Pharm. Res. 20, 330
(1997).
[11] M. A. McCall, J. Org. Chem. 27, 2433 (1962).
[12] J. S. A. Brunskill, A. De, D. F. Ewing, J. Chem. Soc.
Perkin Trans. I, 629 (1987).
[6] F. A. Attaby, S. M. Eldin, E. A. Hanafi, J. Pharm.
Res. 20, 620 (1997).
[13] P. Chabrier, L. Pallu, C. R. Acad. Sei. (Paris) 220,
363 (1945).
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