Heterocyclic synthesis containing new spiro, isolated (β-lactam and thiazolidinone) 3-cyano-2, 4- diamino thiophene derivatives

Article abstract of DOI:10.1080/10426500701724548

The reaction of acetamide and malononitrile with elemental sulfur in ethanol containing piperidine catalyst afforded 3-cyano-2,4-diamino thiophene 1, which readily underwent condensation reaction with different aromatic aldehydes to yield Schiff bases (2a

Full text of DOI:10.1080/10426500701724548

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Phosphorus, Sulfur, and Silicon
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Heterocyclic Synthesis
Containing New Spiro, Isolated
(β -Lactam and Thiazolidinone)
3-Cyano-2, 4- Diamino
Thiophene Derivatives
H. A. Soleiman a & N. A. A. Elkanzi a
a Chemistry Department, Faculty of Science , South
Valley University , Aswan, Egypt
Published online: 24 Jun 2008.
To cite this article: H. A. Soleiman & N. A. A. Elkanzi (2008) Heterocyclic Synthesis
Containing New Spiro, Isolated (β -Lactam and Thiazolidinone) 3-Cyano-2, 4- Diamino
Thiophene Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements,
183:7, 1679-1690, DOI: 10.1080/10426500701724548
To link to this article: http://dx.doi.org/10.1080/10426500701724548
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Phosphorus, Sulfur, and Silicon, 183:1679–1690, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701724548
Heterocyclic Synthesis Containing New Spiro, Isolated
(β-Lactam and Thiazolidinone) 3-Cyano-2, 4- Diamino
Thiophene Derivatives
H. A. Soleiman and N. A. A. Elkanzi
Chemistry Department, Faculty of Science, South Valley University,
Aswan, Egypt
The reaction of acetamide and malononitrile with elemental sulfur in ethanol con-
taining piperidine catalyst afforded 3-cyano-2,4-diamino thiophene 1, which read-
ily underwent condensation reaction with different aromatic aldehydes to yield
Schiff bases (2a–c) Cyclization of (2a–e) by refluxing with chloroacetyl chloride
and/or mercaptoacetic acid afforded new (β-lactam (3a–c) and New thiazolidinone
(4a–c) derivatives, respectively. In addition, 1 reacted with chloroacetyl chloride in
presence of ethanol and triethylamine to give 6. compound 6 react with different
nitroso compounds to give Schiff bases (7a–c) which underwent cyclization with
chloroacetyl chloride and/or mercaptoacetic acid to give spiro (β-lactam (8a–c)
and spiro thiazolidinone derivatives (9a–c), respectively. Also, 6 reacts with differ-
ent aromatic amines in presence of ethanol and piperidine catalyst to give Schiff
bases (10a–c), cyclization of (10a–c) with chloroacety1chloride and/or mercap-
toacetic acid afforded spiro β-lactam (11a–c) and Spiro thiazolidine derivatives
(12a–c).
Keywords Thiophene derivatives
INTRODUCTION
β-lactams and related derivatives have been found to be ac-
tive compounds having antibacterial activities. Some examples com-
prise the naturally occurring monobactams and nocardicins.1 Con-
trary to penicillins, cephalosporins, or nocardicins, monobactams were
not produced by fungi or actinomycetes, but from bacteria, for ex-
ample Bacillus, pseudomonas.2 Nocardicins proved the relationship
with cephalosporins and penicillins via the corresponding Configura-
tion at C3, but they have no therapeutic significance. The synthetic
oxamazins,3−5 thiamazins,6 and monosulfactams7 showed some an-
tibacterial activity, which raised again a major interest in the area of
Received 16 July 2007; accepted 4 August 2007.
Address correspondence to H. A. Soleiman, Chemistry Department, Faculty of Science,
South Valley University, Aswan, Egypt. E-mail: hsoleiman2001@yahoo.com
1679

1680
H. A. Soleiman and N. A. A. Elkanzi
2-azetidinone chemistry. Also thiazole derivatives such as penicillins
which have fused thiazolidine and β-lactam rings were known and used
as potent antibiotics.8 Thiazole derivatives are also associated with a
broad spectrum of biological properties, including anticonvulsant,9,10
antimicrobial,11,12 antituberculous,13 and bacteriostatic activities,14,15
Therefore, compounds containing (β-lactam ring, thiazolidinone are
expected to possess potential biological activities. Our previous work
aimed at developing new approaches to the synthesis of polyfunction-
ally substituted heterocyclic compounds of biological activity.16−18
RESULTS AND DISCUSSION
Herein, we report the synthesis of heterocyclic compounds containing
the aforementioned rings via readily available 3-cyano-2, 4-diamino
thiophene 1. Compound 1, which reacts with different aromatic aldehy-
des to give new Schiff bases 3-cyano-2, 4-diarylazamethine thiophene
2a–c. The proposed formulation of compound 2a–c was confirmed by
mass spectrum and elemental analysis (c.f. Table I), IR spectrum which
revealed a characteristic band [KBr] at 1580 cm−1 (C N) and 1H NMR
spectrum which showed signal at δ 7.12(s, 2H, 2N CH). Schiff based
2a–c reacts with chloroacetylchloride and/or mercaptoacetic acid to af-
ford β-lactam derivatives 3a–c and thiazolidinone derivatives 4a–c. The
proposed formulation of compounds 3a–c and 4a–c were confirmed by
mass spectrum and elemental analysis (c.f. Table I), IR spectral which
1
revealed characteristic peak [KBr] at 1760 cm−1 (C O) and H NMR
spectrum of 4a and 4a as example which showed signal at δ 6.43(s, 1H,
CH), 5.83(s, 2H, 2NCH5), 2.5(s, 4H, 2CH2) respectively. The activation
exerted by the cyano group at C3 on the exocyclic amino group at C4
render it available for the condensation with chloroacetylchloride to
give compound 5 or 6. At first, our theoretical conception of the obvious
cycloaddition reaction leads to the formation of compound 5. But, the
experimental evidence that depends on the different types of analysis to
the reaction product proves that the cycloaddition reaction leads to the
formation of compound 6 through the electronic cyclization according to
the suggested mechanism (Scheme 2 illustrates the formation of com-
pound 6). The proposed formulation of compound 6 was confirmed by
mass spectrum and elemental analysis (c.f. Table I); IR spectral that
revealed characteristic peaks (KBr) at γ 3340 cm−1 3160 cm−1(NH
1
and NH2), 2217 cm−1(CN), 1675 cm−1(C O), and H NMR spectrum
(DMSO-d6), which showed signal at δ 9.25(s, 1H, NH), 5.22(brs, 2H,
NH2), 4.65(s, 2H, CH2). Reaction of compound 6 with different aromatic
nitroso compounds to give the corresponding Schiff bases (7a–c). The
proposed formulation of 7a–c were confirmed by mass spectrum and

New Spiro Thiophene Derivatives
1681
TABLE I Characterization of Compounds (1–12)
Analysis % calcd. (found)
Comp.
no.
M.P.
C
Solvent Yield
M.F.
(M. Wt.)
of cryst.
%
C
H
N
M.S.
139
1a
2a
2b
2c
3a
3b
3c
4a
4b
4c
6
227–229
Ether
80
C5H5N3S
(139.17)
C19H17N3S
(319.42)
19H17N3O2S
(351.42)
19H17N5SO4
(411.44)
43.15 3.62
30.19
(43.25) (3.53) (30.16)
71.93 5.35 3.15
(71.96) (5.23) (13.05)
64.93 4.88 11.96
(64.46) (4.95) (11.98)
55.47 4.16 17.02
(55.50) (4.15) (17.00)
244–246 Ethanol
249–251 Ethanol
265–267 Ethanol
284–286 Dioxane
289–291 Dioxane
298–300 Dioxane
252–254 Ethanol
264–266 Ethanol
271–273 Ethanol
239–241 Dioxane
67
70
73
68
66
319
351
411
472
500
562
463
479
521
321
410
284
345
344
360
395
342
358
387
254
412
C
C
C
23H19N3O2Cl2S 58.47 4.06
(472.39) (58.28) (4.01)
23H19N3O4SCl2 55.21 3.02
(500.36) (55.25) (3.01)
69 C23H17N5O6SCl2 49.48 2.35
8.89
(8.36)
8.40
(8.60)
12.54
C
(558.35)
C23H17N3O2S3
(463.59)
C23H17N3O3S3
(479.59)
C23H15N5O4S3
(521.58)
C7H5N3OS
(321.34)
17H10N4O2S
(410.43)
C13H8N4O2S
(284.00)
C15H13N5OS
(345)
19H11N4O3SCl 52.26 2.63
(49.40) (2.40) (12.54)
73
72
70
78
59.59 3.70
(59.66) (3.67)
57.60 3.57
(57.50) (3.64)
52.96 2.90
9.06
(9.02)
8.76
(8.80)
13.43
(52.90) (2.85) (13.03)
26.16 1.57 13.08
(26.31) (1.63) (13.30)
38.04 1.96 13.65
(38.10) (2.00) (13.55)
54.92 2.84 19.71
(54.82) (2.89) (19.59)
45.22 2.04 20.28
(45.25) (2.15) (20.35)
16.25
(52.30) (2.50) (16.30)
49.94 2.52 15.53
(49.79) (2.59) (15.46)
17.69
(45.55) (3.57) (17.73)
52.62 2.49 16.36
(52.55) (2.90) (16.40)
50.27 2.81 15.63
(50.16) (2.70) (15.60)
46.51 2.34 18.08
(46.35) (2.30) (18.00)
61.40 3.96 22.03
(61.46) (3.97) (22.01)
37.86 2.44 13.58
(37.80) (2.40) (13.58)
(Continued on next page)
7a
7b
7c
8a
8b
8c
9a
9b
9c
10a
10b
279–281 Methanol 68
274–276 methanol 66
285–287 Methanol 70
289–291 Methanol 84
295–297 Methanol 82
297–299 Methanol 81
C
C
(344.78)
15H9N4O3SCl
(360.77)
C
C17H14N5O2SCl 45.52 3.57
(395.82)
18H12N4O3S2
(342.39)
C14H10N4O3S2
(358.39)
C16H15N5O2S2
(387.39)
13H10N4S
(254.31)
13H9N5O2S
(412.45)
252–254 Ethanol
264–266 Ethanol
271–273 Ethanol
73
73
70
C
288–300 Methanol 68
289–291 Methanol 66
C
C

1682
H. A. Soleiman and N. A. A. Elkanzi
TABLE I Characterization of Compounds (1–12) (Continued)
Analysis % calcd. (found)
Comp.
no.
M.P.
C
Solvent Yield
of cryst.
M.F.
(M. Wt.)
%
C
H
N
M.S.
299
10c
11a
11b
11c
12a
12b
12c
285–287 Methanol 70
295–297 Methanol 84
290–292 Methanol 82
278–280 Methanol 81
C13H9N4SCl
(299.31)
52.17 3.03
23.40
(52.24) (3.10) (23.36)
16.99
(54.70) (3.15) (16.90)
15H10N5O3SCl 51.95 3.20 16.16
(346.79) (51.80) (3.25) (16.20)
15H10N4OSCl2 47.94 2.68 18.64
(48.00) (2.60) (18.70)
C15H11N4OSCl 54.63 3.06
(329.78)
329
346
375
628
344
373
C
C
(507.38)
15H12N4OS2
(628.69)
262–264 Ethanol
274–276 Ethanol
269–271 Ethanol
73
C
28.70 1.77
(28.60) (1.84)
8.93
(8.88)
16.27
272
C
15H11N5O3S2 52.31 3.51
(344.41)
170 C15H11N4OS2Cl 48.25 2.97
(373.40) (48.37) (3.03) (18.67)
(52.52) (2.70) (16.38)
18.76
elemental analysis (c.f. Table I), IR spectral which revealed a charac-
teristic peaks (KBr) at 3398(OH), 3345–3170 cm−1(NH and NH2), 2210
1
cm−1(CN), 1680 cm−1 (C O) and H NMR spectrum (DMSO-d6) at δ
9.88(s, 1H, NH), 8.45–7.32 (m, 5H, Ar-H+, OH), 5.55 (brs, 2H, NH2).
NH
C
NC
CN
NC
CN
NC
O
C
CN
CN
Dioxane/pip.
C
C
C
C
C
C
S
S
H3C
NH2
H2C
+
CH2
H2N
CH3
H2N
CH2SH
H2N
O
Cl
N
NC
DMA/T.E.A
H2C Cl
S
R
R
R
N
N
C
H
NH2
R
NC
OHC
DMF/pip.
NC
Cl
O
O
OC Cl
S
S
R
(3a-c)
N
H2N
(2a-c)
( 1 )
S
R
N
NC
S
R
HCH2COOH
N
S
3-4a; R = H
b; R = OH
O
(4a-c)
c; R = NO2
SCHEME 1

New Spiro Thiophene Derivatives
1683
NH
2
NH
2
NH
2
NH
R
NC
2
NC
NC
S
S
S
ON
NC
Ethylene glycol
S
OC
Cl
CH
2
+
R
T.E.A.
SHCH2COOH
H
Cl
HN
HN
HN
Cl
CH2
H2N
( 1 )
C
O
N
O
O
( 6 )
(7a-c)
Cl
OC
Cl
CH
NH
2
2
T.E.A.
SHCH2COOH
NC
S
T.E.A.
NH
2
O
H2N
Cl
R
NC
C
H2
S
NH
2
R
NC
HN
N
S
S
NH
2
20
O
O
Cl
(8a-c)
HN
N
NC
O
S
O
(9a-c)
SCHEME 2
Treatment of an ethanolic solution of 7a-c with chloroacetylchloride
and/or mercaptoacetic acid in the presence of triethylamine afforded
the corresponding new Spiro β-lactam (8a–c) and new Spiro thiazolidi-
none (9a–c). The proposed formulations of 8a–c and 9a–c were con-
firmed by mass spectrum and elemental analysis (c.f. Table I); IR spec-
tral, which revealed a characteristic peaks of 8a and 9a as example
(KBr) at 3396 cm−1 (OH), 3346, 3177 cm−1(NH, NH2), 2216 cm−1(CN),
1765 cm−1(C O), and 3396 cm−1(OH), 3190, 3186 cm−1 (NH, NH2),
2215(CN), 1765 cm−1(C O), respectively. 1H NMR spectrum of 8a and
9a as example which showed signals at δ 9.75(s, 1H, NH), 8.45–7.33(m,
8H, ArH+; β-lactam H+), 5.42(brs, 2H, NH2), and at δ 9.86(s, 1H, NH),
8.23–7.12(m, 8H, Ar-H+), 6.23(s, 1H, CH), 5.42(brs, 2H, NH2), 2.58(s,
2H, CH2), respectively.
Also, the reaction of 6 with different aromatic amines in ethanol in
the presence of piperidine catalyst gives the corresponding new Schiff
bases (10a–c). The structure of 10 a–c was confirmed by mass spectrum
and elemental analysis (c.f. Table I) and IR spectral which revealed a
characteristic bands (KBr) of 12 a as example at 3345, 3176 cm−1(NH,
NH2), 2217 cm−1(CN), 1225 cm-1(C N), and 1H NMR spectrum of 10a
as example (DMSO-d6) which showed signal at δ 9.17(s, 1H, NH), 8.45–
7.32(m, 5H, Ar-H+), 5.36(brs, 2H, NH2), 2.58(s, 2H, CH2).
Reaction of 10a–c with chloroacetylchloride and/or mercaptoacetic
acid in presence of ethanol as solvent and triethylamine as a catalyst
give the corresponding Spiro β-lactam (11a–c) and Spiro thiazolidinone
(12a–c).

1684
H. A. Soleiman and N. A. A. Elkanzi
NH2
NH2
R
NC
NC
S
S
H2N
EtOH/pip.
HN
O
HN
N
(10a-c)
( 6 )
R
Cl
Cl
OC
CH2
T.E.A.
SHCH2COOH
T.E.A.
NH2
NC
NH2
S
NC
S
HN
N
HN
R
N
O
Cl
R
S
(11a-c)
O
(12a-c)
10-12: a; R = H
b; R = 4-NO2
c; R = 4-Cl
SCHEME 3
The proposed formulations of 11a–c and 12a–c were confirmed by
mass spectral and elemental analysis (c.f. Table I) and IR spectrum
which revealed a characteristic peaks (KBr) of 11a and 12a as exam-
ples at 3356, 3177 cm−1(NH, NH2), 2214 cm−1(CN), 1766 cm−1(C O),
1226 cm−1(C N) and 3100–3189 cm−1(NH, NH2), 2219 cm−1(CN), 1765
cm−1(C O), 1226 cm−1(C N), respectively, and 1H NMR spectrum,
which showed signals of 11a and 12a as examples (DMSO-d6) at δ
9.78(s, 1H, NH), 8.45–7.32(m, 5H, Ar-H+), and β-lactam-H+), 5.47(brs,
2H, NH2), 2.22(s, 2H, CH2), and at δ 9.88(s, 1H, NH), 8.23–7.12(m,

New Spiro Thiophene Derivatives
1685
5H, Ar-H+), 6.24(s, 1H, CH), 5.47(brs, 2H, NH2), 2.25(s, 4H, 2CH2),
respectively.
EXPRIMENTAL
All melting points are uncorrected; IR spectra were measured as KBr
1
pellets on a Pye Unicam sp 1000 spectrophotometer. H NMR spectra
were recorded in DMSO- d6 at 200 MHz on a Varian Gemini NMR
spectrometer, using TMS as internal reference; the chemical shifts are
expressed as δ Values (ppm). Mass spectra were obtained on a Shimadzu
GCMS- Qp 1000 EX mass spectrometer at 70 eV. Elemental analyses
were carried out at the micro analytical center of Cairo University.
Synthesis of 2, 4-Diamino 3-Cyano Thiophene (1)
A solution of appropriate amount of acetamide (0.59 g, 1 mmol) and
malononitrile (0.66 g, 1 mmol) was added with sulfur (0.32 g, 1 mmol)
in presence of (0.5 ml) of piperidine catalyst and dioxane as solvent.
The reaction mixture was heated under reflux for 12 h, concentrated
in vacuum, cooled, and diluted with ice water acidified by concentrated
hydrochloric acid. The precipitate obtained was filtered, washed with
ice water, dried, and recrystallized from diethyl ether to afford 1.
Synthesis of 2,4 Diarylazamethine Phenyl-3-Cyano Thiophene
(2a–c)—General Procedures
To a stirred solution of 2,4-diamino-3-cyano-thiophene 1 (I.39g, 1mmol)
in DMF (20 ml), different aromatic aldehydes (2.22 g, 2 mmol; 2.44 g, 2
mmol; 3.02 g, 2 mmol, respectively) in presence of (0.5 ml) of piperidine
catalyst. The reaction mixture was heated on a boiling water bath for 7
h, then left to cool until it reached 25◦C. The reaction mixture diluted
with ice water (40 ml) and neutralized with hydrochloric acid. The solid
product formed on standing overnight was filtered, washed thoroughly
with cold water, and dried, recrystallization from ethanol to yield the
corresponding (2a–c), (c.f. Tables I, II).
Synthesis of 2, 4-Dimono Substituted β-Lactam
Arylazamethine Phenyl 3 Cyano Thiophene (3a–c)—General
Procedures
A mixture of (2a–c) (3.19 g, 1 mmol; 3.51 g, 1 mmol; 4.11 g, 1 mmol
respectively) and chloroacetylchloride (1.13 g, 2 mmol) in DMF in
presence of (0.5 ml) of triethylamine was refluxed in water bath for

1686
H. A. Soleiman and N. A. A. Elkanzi
TABLE II IR, 1H NMR Spectral Data of Compound
Comp. no. IR (cm)−1
1H NMR (δ-ppm)
1
2a
3350-3340(NH2), 2220(C N).
2216(C N), 1580(C N).
5.35(brs, 4H, 2NH2), 6.41(s, 1H, CH).
6.35(s, 1H, CH), 7.12(s, 2H, CH N),
7.32–8.45(m, 10H, Ar H+).
2b
2c
3a
3b
3c
4a
3450(OH), 2212(C N),
1585(CH N).
1596(CH N), 2206(C N).
6.25(s, 1H, CH), 7.13(s, 2H, 2CH N),
7.33–8.42(m, 10H, Ar H+).
6.45(s, 1H, CH), 7.13(s, 2H, 2CH N),
7.33–8.45(m, 8H, Ar H+).
1222(C-N), 1760(C O), 2218(C N). 6.43(s, 1H, CH), 7.35-8.45(m, 8H,
Ar H+& β−lactam H+).
1226(C-N), 3440(OH), 1765(C O), 6.38(s, 1H, CH), 7.33-8.45(m, 8H,
2213(C N), 3440(OH).
1224(C-N), 1763(C O), 2216(C N). 6.36(s, 1H, CH), 7.32-8.45(m, 6H,
Ar H+& β−lactam H+).
Ar-H++ β−lactam H+).
1675(C O), 2213(C N).
2.51(s, 4H, 2CH2), 6.23(s, 1H, CH),
5.83(s, 2H, 2NCH5), 7.12–8.22(m,
10H, Ar H+).
4b
4c
1680(C O), 2210(C N),
3945(2OH).
2.55(s, 4H, 2CH2), 6.33(s, 1H, CH),
5.86(s, 2H, 2NCH5), 7.12-8.33(m,
10H, Ar H+).
2.58(s, 4H, 2CH2), 6.36(s, 1H, CH),
5.88(s, 2H, 2NCH5), 7.12-8.23(m,
8H, Ar H+).
1685(C O), 2206(C N).
7a
7b
7c
3398(OH), 3345–3170(NH, NH2),
1680(C O), 2210(C N).
3395–3176(NH, NH2), 1685(C O), 5.55(brs, 2H, NH2), 9.88(s, 1H, NH),
5.35(brs, 2H, NH2), 9.69(s, 1H, NH),
7.3–8.45(m, 7H, Ar H+ +OH-H+).
2216(C N)
7.32-8.45(m, 5H, Ar H+ +OH).
3350-3175(NH, NH2), 1686(C O), 1.35(s, 6H, 2CH3), 5.33(brs, 2H, NH2),
2206(C N).
9.67(s, 1H, NH), 7.30-8.45(m, 4H,
Ar H+).
8a
8b
8c
9a
9b
9c
1223(C-N), 1765(C O), 2216(C N), 5.42(brs, 2H, NH2), 9.75(s, 1H, NH),
3396(OH), 3346–3177(NH, NH2). 7.33–8.45(m, 8H,
Ar H+ β-lactam-H+)
1225(C-N), 1766(C O), 2213(C N), 5.46(brs, 2H, NH2), 9.85(s, 1H, NH),
3395(OH), 3341-3180(NH, NH2). 7.35–8.45(m, 6H,
Ar H+ β-lactam-H+)
1228(C-N), 1768(C O), 2210(C N), 1.22(s, 6H, 2CH3), 5.56(brs, 2H, NH2),
3340-3170(NH, NH2). 9.78(s, 1H, NH), 7.35–8.45(m, 6H,
Ar H+ β-lactam-H+)
+
+
+
1675(C O), 2215(C N), 3396(OH), 5.42(brs, 2H, NH2), 9.86(s, 1H, NH),
1228(C-N), 3186(NH, NH2).
7.12–8.23(m, 8H, Ar H+), 2.58(s,
2H, CH2), 6.23(s, 1H, CH).
1680(C O), 2208(C N), 3398(OH), 5.45(brs, 2H, NH2), 9.88(s, 1H, NH),
1224(C-N), 3180(NH, NH2).
7.32–8.45(m, 4H, Ar H+), 2.58(s,
2H, CH2), 6.35(s, 1H, CH).
1.23(s, 6H, 2CH3), 5.36(brs, 2H, NH2),
9.80(s, 1H, NH), 7.32–8.45(m, 4H,
Ar H+), 2.58(s, 2H, CH2), 6.33(s,
1H, CH).
1675(C O), 2210(C N),
1224(C-N), 3187(NH, NH2).
(Continued on next page)

New Spiro Thiophene Derivatives
1687
TABLE II IR, 1H NMR Spectral Data of Compound (Continued)
Comp. no. IR (cm)−1
1H NMR (δ-ppm)
10a
3345-3176(NH, NH2), 2217(C N), 5.36(brs, 2H, NH2), 9.71(s, 1H, NH),
1225(C N).
2.58(s. 2H, CH2), 7.32–8.45(m, 5H,
Ar H+).
10b
10c
11a
3340-3186(NH, NH2), 2221(C N), 5.46(brs, 2H, NH2), 9.73(s, 1H, NH),
1223(C N).
3355-3178(NH, NH2), 2245(C N), 5.39(brs, 2H, NH2), 9.69(s, 1H, NH),
7.31-8.45(m, 4H, Ar H+).
12228(C-N).
7.31-8.45(m, 4H, Ar H+).
5.47(brs, 2H, NH2), 9.78(s, 1H, NH),
7.32–8.45(m, 5H,
1226(C-N), 2214(C N),
3356-3177(NH, NH2),
1766(C O).
1224(C-N), 1770(C O), 2210(C N), 5.46(brs, 2H, NH2), 9.85(s, 1H, NH),
3345-3180(NH, NH2). 7.35–8.45(m, 6H,
Ar H+ β-lactam-H+).
1221(C-N), 1768(C O), 2206(C N), 5.56(brs, 2H, NH2), 9.78(s, 1H, NH),
Ar H+
+
β-lactam-H+).
11b
11c
12a
+
3340-3170(NH, NH2).
7.35–8.45(m, 6H,
Ar H+ β-lactam-H+).
+
1765(C O), 2219(C N),
1226(C-N), 3189(NH, NH2)
5.47(brs, 2H, NH2), 9.88(s, 1H, NH),
7.12–8.23(m, 8H, Ar H+), 2.25(s,
4H, 2H2), 6.24(s, 1H, CH).
12b
12c
1766(C O), 2214(C N),
1224(C-N), 3187(NH, NH2)
1765(C O), 2210(C N),
1226(C-N), 3187(NH, NH2)
5.55(brs, 2H, NH2), 9.88(s, 1H, NH),
7.32–8.45(m, 4H, Ar H+).
5.46(brs, 2H, NH2), 9.82(s, 1H, NH),
7.32–8.45(m, 4H, Ar H+), 2.15(s,
4H, 2CH2), 6.33(s, 1H, CH).
15 h. After removal the DMF under reduced pressure, the result-
ing solid product was filtered and washed with water. The crude
product was recrystallized form dioxane to yield the corresponding
(3a–c).
Synthesis of 2, 4-Dithiazolidinone Arylaza Methine
Phenyl-3-Cyano Thiophene (4a-c)—General Procedures
A mixture of (2a–c) (3.19 g, 1 mmol; 3.51 g, 1 mmol; 4.11 g, 1 mmol re-
spectively) and mercaptoacetic acid (1.84 g, 2 mmol) was refluxed in dry
benzene (30 ml) in presence of triethylamine (using a Dean–stark water
separator). The excess benzene was evaporated in vacuum. The result-
ing residue was triturated with ice water naturalized by concentrated
hydrochloric acid and was allowed to stand overnight. The solid thus
obtained washed with water, dried, and recrystallized from ethanol to
yield the corresponding (4a–c).

1688
H. A. Soleiman and N. A. A. Elkanzi
Synthesis of Compound (6)
A solution of 1 (1.39 g, l mmol) in ethylene glycol (30 ml) and
chloroacety1chloride (l.13 g, 1 mmol) in presence of (0.5 ml) of tri-
ethylamine was heated under reflux for 12–15 h (TLC control). After
removal of the ethylene glycol under reduced pressure, the resulting
solid product was filtered and washed with water. The crude product
was recrystallized from dioxane to yield the 6.
Synthesis of New Schiff Bases (7a–c)—General Procedures
To a solution of 6 (1.79 g, 1 mmol) in ethanol (25 ml), different aromatic
nitroso compound (1.73 g, 1 mmol; 1.73 g, 1 mmol; 1.23 g, 1 mmol,
respectively) in presence of piperidine (0.5 ml) as catalyst. The reac-
tion mixture was heated under reflux for 4–5 h; the solvent was then
evaporated under reduced pressure. The residue treated with ice water
was neutralized by concentrated hydrochloric acid. The solid product
so formed was collected by filtration and recrystallized from methanol
to yield the corresponding (7a–c).
Synthesis of Spiro β-Lactam (8a–c)—General Procedures
A mixture of 7a–c (4.1 g, 1 mmol; 2.84 g, 1 mmol; 3.45 g, 1 mmol respec-
tively) and chloroacetylchloride (l.13 g, 1 mmol) in dioxane in presence
of (0.5 ml) of triethylamine was heated under reflux for 13 h. The sol-
vent removed under reduced pressure, the resulting solid product was
filtered and washed with water. The crude product was recrystallized
from methanol to yield the corresponding 8a–c, (c.f. Table I, II).
Synthesis of Spiro Thiazolidinone 9a–c—General Procedures
A mixture of 7a–c (4.1 g, 1 mmol; 2.84 g, 1 mmol; 3.45 g, 1 mmol re-
spectively) and meracaptoacetic acid and (0.92 g, 1 mmol) was refluxed
in dry benzene (30 ml) in presence of triethylamine using a Dean-stark
water separator. The excess of benzene was evaporated in vacuum. The
resulting residue was triturate with ice water neutralized by concen-
trated hydrochloric acid and was allowed to stand overnight the solid
was recrystallized from ethanol to yield corresponding 9a–c, (c.f. Tables
I, II).
Synthesis of New Schiff Bases (10a–c)—General Procedure
To a solution of 6 (1.79 g ,1 mmol) in ethanol (25 ml) , different aro-
matic amino compound (0.92 g, 1 mmol; 1.38 g, 1 mmol; 1.57 g, 1 mmol,

New Spiro Thiophene Derivatives
1689
respectively) in presence of piperidine (0.5 ml) as catalyst. The reac-
tion mixture was heated under reflux for 4–5 h; the solvent was then
evaporated under reduced pressure. The residue treated with ice wa-
ter neutralized by concentrated hydrochloric acid. The solid product so
formed was collected by filtration and recrystallized from methanol to
yield the corresponding 10a–c, (c.f. Tables I, II).
Synthesis of Spiro β-Lactam (11a–c)—General Procedure
A mixture of 10a–c (2.54 g, 1 mmol; 4.12 g, 1 mmol; 2.99 g, 1 mmol,
respectively) and chloroacetyl chloride (1.13 g, 1 mmol) in dioxane in
presence of (0.5 ml) of triethylamine was heated under reflux for 13
h. The solvent removed under reduced pressure, the resulting solid
product was filtered and washed with water. The crude product was re-
crystallized from methanol to yield the corresponding 11a–c (c.f. Table
I, II).
Synthesis of Spiro Thiazolidine (12a–c)—General Procedure
A mixture of 10a–c (2.54 g, 1 mmol; 4.12 g, 1 mmol; 2.99 g, 1 mmol
,respectively ) and mercaptoacetic acid (0.92 g, 1 mmol) was refluxed
in dry benzene 30 ml in presence of triethylamine using a Dean stark
water separator the excess of benzene was evaporated in vacuum. The
resulting residue was triturated with ice water neutralized by concen-
trated hydrochloric acid and was allowed to stand overnight. The solid
was recrystallized from ethanol to yield the corresponding 12a–c (c.f.
Tables I, II).
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