Synthesis and reactions of some new spiropyranthiazoline derivatives

Article abstract of DOI:10.1080/10426500701849287

Pyrano[2,3-d]thiazoline-7-spiro-3'-(1'-substitutedindoline-2'-ones) 5a,b has been synthesized and reacted with some nucleophile reagents to afford new spirothiazolino[4,5:2',3']pyrano[6',5'-d]pyrimidine derivatives 6a,b-13a,b, which are analogues of some

Full text of DOI:10.1080/10426500701849287

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Phosphorus, Sulfur, and Silicon
and the Related Elements
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Synthesis and Reactions of
Some New Spiropyranthiazoline
Derivatives
Maher F. El-Zohry a , Yasser A. Elossaily a , Thanaa A.
Mohamed a & Essam M. Hussein a
a Chemistry Department, Faculty of Science , Assiut
University , Assiut, Egypt
Published online: 12 Aug 2008.
To cite this article: Maher F. El-Zohry , Yasser A. Elossaily , Thanaa A. Mohamed &
Essam M. Hussein (2008) Synthesis and Reactions of Some New Spiropyranthiazoline
Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements, 183:9,
2095-2107, DOI: 10.1080/10426500701849287
To link to this article: http://dx.doi.org/10.1080/10426500701849287
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Phosphorus, Sulfur, and Silicon, 183:2095–2107, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701849287
Synthesis and Reactions of Some New
Spiropyranthiazoline Derivatives
Maher F. El-Zohry, Yasser A. Elossaily,
Thanaa A. Mohamed, and Essam M. Hussein
Chemistry Department, Faculty of Science, Assiut University,
Assiut, Egypt
Pyrano[2,3-d]thiazoline-7-spiro-3ꢀ-(1ꢀ-substitutedindoline-2ꢀ-ones) 5a,b has been
synthesized and reacted with some nucleophile reagents to afford new
spirothiazolino[4,5:2ꢀ,3ꢀ]pyrano[6ꢀ,5ꢀ-d]pyrimidine derivatives 6a,b–13a,b, which
are analogues of some reported biologically active spiroheterocyclic compounds.
Keywords Indoline; Pyranothiazolidine; Spiro; Spiroheterocyclic; Thiazolinopyranopy-
rimidine
INTRODUCTION
Spiro derivatives have anticonvulsants, antibacterial and anticancer
activities.1,2 Spiro heterocycles were used as nitric oxide synthesis
inhibitors,3 photoisomerization,4,5 and potential topical agents for
vaginal infection.6 Photochromism of indolinospirochromenes contain-
ing condensed fragments in the indoline part of the molecule were
achieved.7 Nitrils were used as starting materials to prepare a ver-
ity of condensed pyrans8–12 for their medicinal importance.13,14 Pyrano
derivatives have well-known biological effects, such as analgesic and
anti-inflammatory activities,15 and pyrimidine derivatives have been
used as adenosine kinase inhibitors.16 Further, spiropolycycles were im-
portant for the synthesis of ptilomycalin A and fredricmycine A models,
which was used as an antitumor agent. Our continuing interest in this
area18–25 encouraged us to suggest the synthesis of some new spiropoly-
cycles of pyranothiazoline.
Received 20 August 2007; accepted 24 October 2007.
Address correspondence to Maher F. El-Zohry, Chemistry Department, Faculty of Sci-
ence, Assiut University, Assiut 71516, Egypt. E-mail: mfzohry@yahoo.com
2095

2096
M. F. El-Zohry et al.
RESULTS AND DISSCUSION
Our syntheses started with the reaction of benzophenone 1 with
mercaptoacetic acid in dry toluene18 and catalytic amount of p-
toluenesulphonic acid to yield 2,2-diphenyloxathiolidine-4-one 2, which
then reacted with benzyl amine in absolute ethanol to afford 3-benzyl-
2,2-diphenylthiazolidine-4-one 3 in good yield.
Compound 3 reacted with 3-dicyanomethylidine-2-oxoindolines 4a,b
in refluxed ethanol and catalytic amount of triethyl amine to af-
ford pyrano[2,3-d]thiazoline-7-spiro-3ꢀ-(1ꢀ-substitutedindoline-2ꢀ-ones)
5a,b, via a type of Michael addition shown in (Scheme 1).
The structures of the prepared compounds 2, 3, and 5a,b were es-
tablished from their elemental analyses and spectral data. The IR spec-
trum of compound 2 showed absorption bands at υ´ 1700 and 690 cm−1
for the carbonyl group of the oxathiolidine ring and C S bond respec-
1
tively. The H NMR spectrum of compound 2 revealed the presence of
a singlet signal of two protons at δ 3.90 assignable to the methylene
protons and multiplet signal of ten protons at 7.85–6.90 for the aro-
matic protons. The 1H NMR spectrum of compound 3 revealed showed
a singlet signal of two protons at δ 3.95 assignable to the methylene
protons in the thiazolidine ring and a singlet signal of two protons at
δ 2.96 for the methylene protons in the benzyl group.
The IR spectrum of compound 5a showed characteristic absorption
bands at υ´ 3320, 3260, 2200, and 1710 cm−1 corresponding to NH2, NH,
CN, and C O groups respectively. Its 1H NMR spectrum showed multi-
plet signal at δ 7.71–6.61 for aromatic protons and three singlet signals
at 10.35, 5.00, and 3.51 for NH, NH2, and CH2 protons, respectively.
However, the IR spectrum of compound 5b showed absorption bands at
υ´ 3340–3200, 2200, and 1705 cm−1 corresponding to NH2, CN, and C O
groups, respectively. Its 1H NMR spectrum showed multiplet signal at
δ 7.89–6.75 for aromatic protons and three singlet signals at 5.02, 3.24,
and 2.51 for NH2, CH3, and CH2 protons, respectively.
However, compounds 5a,b represents a good synthon for pyrim-
idines synthesis, which found considerable interest in field of medicine
and biology.26–28 Compounds 5a,b refluxed with formic acid to afford

New Spiropyranthiazoline Derivatives
2097
SCHEME 1
3-benzyl-2,2-diphenyl-7(H)-8-oxothiazolino[4,5:2ꢀ,3ꢀ]pyrano[6ꢀ,5ꢀ-d] py-
rimidine-9-spiro-3ꢀ(2ꢀ-oxoindoline) derivatives 6a,b.
Reaction of 5b with acetic anhydride/pyridine mixture gave 3-benzyl-
2,2-diphenyl-7(H)-8-oxo-6-methylthiazolino[4,5:2ꢀ,3ꢀ]pyrano[6ꢀ,5ꢀ-d]py-
rimidine-9-spiro-3ꢀ(1ꢀ-methyl indolin-2ꢀ-one) 7 (Scheme 2). Comp-
ounds 6a,b and 7 were formed via Dimruth rearrangement illustrated
in (Scheme 2).

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M. F. El-Zohry et al.
SCHEME 2
The IR spectrum of compounds 6a, 6b, and 7 revealed absorption
bands at υ´ 3250, 3300, and 3500, respectively, which corresponded to
the NH group with disappearance of the absorption bands correspond-
1
ing to the cyano and amino groups. The H NMR spectrum of com-
pounds 6a and 6b revealed a singlet signal for one proton at δ 5.49–5.40
exchanged with D2O indicated to NH proton with absence of the sig-
1
nal corresponding to NH2 protons. However, the H NMR spectrum of
compound 7 revealed a singlet signal at δ 5.40 exchanged with D2O

New Spiropyranthiazoline Derivatives
2099
for NH proton, and two singlet signals at 3.39 and 2.10 for two methyl
protons.
Interaction of 5a,b with formamide afforded 8-amino-3-benzyl-
2,2-diphenylthiazolino[4,5:2ꢀ,3ꢀ]pyrano[6ꢀ,5ꢀ-d]pyrimidine-9-spiro-3ꢀ(1ꢀ-
substitutedindolin-2ꢀ-one) 8a,b. Reaction of 5a,b with malononitrile
in glacial acetic acid under reflux gave the corresponding spiro-
thiazolino[4,5:2ꢀ,3ꢀ]pyrano[6ꢀ,5ꢀ-d]pyrimidine derivatives 9a,b rather
than spirothiazolino[4,5:2ꢀ,3ꢀ]pyrano[6ꢀ,5ꢀ-b]pyridine derivatives 10a,b.
Reaction of 5a,b with phenylisocyanate in refluxed pyridine af-
forded 5(H)-3-benzyl-8-imino-6-oxo-2,2,7-triphenylthiazolino[4,5:2ꢀ,3ꢀ]
pyrano[6ꢀ,5ꢀ-d]pyrimidine-9-spiro-3ꢀ(1ꢀ-substitu-tedindolin-2ꢀ-one) 11a,
b. The reaction of 5a,b with triethyl orthoformate in the presence of few
drops of glacial acetic acid gave the corresponding 3-benzyl-6-cyano-
2,2-diphenyl-5-ethoxymethiniminopyrano[2,3-d]thiazolino-7-spiro-3ꢀ-
(1ꢀ-substitutedindoline-2ꢀ-ones) 12a,b. Finally, compounds 12a,b re-
acted with hydrazine hydrate to afford 7-amino-3-benzyl-2,2-diphenyl-
8-iminothiazolino[4,5:2ꢀ,3ꢀ]pyrano[6ꢀ,5ꢀ-d]pyrimidine-9-spiro-3ꢀ(1ꢀ-sub-
stitutedindolin-2ꢀ-one) 13a,b. (Scheme 3).
The chemical structures of all compounds 8a,b–13a,b were estab-
lished based on their elemental and spectral analyses. The IR spectrum
of compounds 8a and 8b revealed absorption band at υ´ 3360–3210
corresponding to NH2 group with disappearance of the absorption
band corresponding to the cyano group. The structures of 8-amino-
3-benzyl-6-cyanomethyl-2,2-diphenylthiazolino[4,5:2ꢀ ,3ꢀ ]pyrano[6ꢀ,5ꢀ–
d]pyrmidine-9-spiro-3ꢀ -(Nꢀ -substitutedindolin-2ꢀ -ones) 9a,b were ten-
1
tatively preferred for these products based on its H NMR spectrum
of compound 9b for example, shown the following signals: four singlet
signals at δ 8.39, 3.99, 3.50, and 2.52 for NH, cyanomethyl, methyl,
and methylene protons, respectively.
The IR spectrum of compounds 11a,b shown the absorption bands at
υ´ 3320, and 3290–3280 for two NH groups with absence of the absorp-
tion band corresponding to cyano group. The IR spectrum of compounds
12a,b shown the disappearance of the band for NH2 group, and the 1H
NMR spectrum of compound 12b shown the following signals: multiplet
signals at δ 7.85-6.76 for aromatic protons, quartet and triplet signals
at 4.00 and 1.05 for ethyl protons, and two singlet signals at 3.25 and
2.56 for methyl and benzylic protons, respectively.
The IR spectrum of compounds 13a,b revealed the absorption bands
υ´ 3310–3200 for NH2 group with absence of the band for cyano group
and its 1H NMR spectrum shown the absence of signals corresponding
to ethyl protons.

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M. F. El-Zohry et al.
SCHEME 3
CONCLUSION
The previously discussed reactions described a simple synthetic proce-
dure to prepare new spiroheterocyclic derivatives of pyranothiazolines
and thiazolino- pyranopyrimidines, which might have important bio-
logical applications.

New Spiropyranthiazoline Derivatives
2101
EXPERIMENTAL
The time required for completion of each reaction was monitored by
TLC. Melting points are uncorrected and were measured on a Gallen
Kamp apparatus.
The IR spectra were recorded on a Chimadz 470 IR spectrometer
1
(KBr) υ´ cm−1. The H NMR spectra were measured on Varian EM-
200 MHz spectrometer with TMS as internal standard. Mass spectra
were determined on a Jeol-600 spectrometer. Elemental analyses were
performed on an elemental analyses system GmbH varioel V2.3
.
Synthesis of 2,2-diphenyloxathiolidine-4-one (2)
A mixture of benzophenone 1 (18.2 g, 100 mmol), mercaptoacetic acid
(6.95 mL, 100 mmol), and p-toluenesulphonic acid (0.5 g) in dry toluene
(200 mL) was refluxed for 5 h, whereby the liberated water was removed
by water separator. After cooling, the solvent was removed under vac-
uum, and the oily residue was left at room temperature for three days
to give a solid. The product was treated with Et2O to form a crystalline
product, dried and recrystallized from toluene to give colorless crys-
tals; yield (60%); m.p. 161–163◦C; IR: υ´ cm−1 1700 (C O), 690 (C S);
1H NMR (DMSO-d6): δ 7.81–6.90 (m, 10H, Ar H), 3.90 (s, 2H, CH2);
Anal. calcd. for C15H12O2S (256.13): C, 70.33; H, 4.68; S, 12.49. Found:
C, 69.98; H, 4.67; S, 12.62.
Synthesis of 3-Benzyl-2,2-diphenylthiazolidin-4-one (3)
A mixture of 2 (5.12 g, 20 mmol) and benzyl amine (2.18 mL, 20 mmol)
in absolute ethanol (20 mL) was stirred at room temperature for 4h.
The product was precipitated, collected by filtration, dried and recrys-
tallized from ethanol to give colorless needles; yield (55%); m.p. 158–
160◦C; IR: υ´ cm−1 1710 (C O), 695 (C S); 1H NMR (DMSO-d6): δ 7.89–
6.75 (m, 15H, Ar H), 3.95 (s, 2H, CH2 in thiazolidine ring), 2.96 (s, 2H,
CH2 benzylic); Anal. calcd. for C22H19NOS (345.21): C, 76.53; H, 5.50;
N, 4.05; S, 9.26. Found: C, 76.45; H, 5.46; N, 4.06; S, 9.01.
Synthesis of Compounds 5a,b—General Procedure25
A mixture of 3 (3.45 g, 10 mmol) and 3-dicyanomethylidine-2-
oxoindolines 4a,b (10 mmol) in absolute ethanol (20 mL) in the presence
of TEA (1 mL) was heated under reflux for 6 h. The reaction mixture

2102
M. F. El-Zohry et al.
was cooled to room temperature, and the solvent was removed under
reduced pressure. The formed product was collected by filtration, dried,
and recrystallized from a mixture of ethanol/water (2:1).
5-Amino-3-benzyl-6-cyano-2,2-diphenylpyrano[2,3-
d]thiazolidine-7-spiro-3 ꢀ-(indolin-2 ꢀ-one) (5a)
Pale brown crystals; yield (60%); m.p. 136–138◦C; IR: υ´ cm−1 3320,
3260 (NH, NH2), 2200 (CN), 1710 (C O); 1H NMR (DMSO-d6): δ 10.35
(s, 1H, NH), 7.70–6.61 (m, 19H, Ar H), 5.00 (s, 2H, NH2), 3.51 (s, 2H,
CH2); Anal. calcd. for C33H24N4O2S (540.31): C, 73.35; H, 4.44; N, 10.36;
S, 5.92. Found: C, 73.25; H, 4.36; N, 10.28; S, 6.00.
5-Amino-3-benzyl-6-cyano-2,2-diphenylpyrano[2,3-
d]thiazolidine-7-spiro-3 ꢀ-(1ꢀ-methylindolin-2 ꢀ-one) (5b)
Pale brown crystals; yield (60%); m.p. 120–122◦C; IR: υ´ cm−1 3340–
1
3200 (NH2), 2200 (CN), 1705 (C O); H NMR (DMSO-d6): δ 7.89–6.75
(m, 19H, Ar H), 5.02 (s, 2H, NH2), 3.24 (s, 3H, CH3), 2.51 (s, 2H, CH2);
Anal. calcd. for C34H26N4O2S (554.32): C, 73.66; H, 4.69; N, 10.10; S,
5.77. Found: C, 73.47; H, 4.39; N, 9.98; S, 5.79.
Synthesis of Compounds 6a,b—General Procedure
A mixture of 5a or 5b (5 mmol) and formic acid (5 mL, 85%) was heated
under reflux for 3 h, the reaction mixture was cooled and poured into
an ice/water mixture; the formed solid product was filtered off, dried,
and recrystallized from ethanol.
3-Benzyl-2,2-diphenyl-7(H)-8-oxothiazolino[4,5:2ꢀ,3ꢀ]pyrano
[6ꢀ,5ꢀ-d]pyrimidine-9-spiro-3ꢀ-(indolin-2ꢀ-one) (6a)
Brown crystals; yield (56%); m.p. 120–123◦C; IR: υ´ cm−1 3250 (NH),
1
1705 (C O), 1650 (C N); H NMR (DMSO-d6): δ 10.31 (s, 1H, NH in-
doline), 8.13–6.83 (m, 20H, Ar H and CH pyrimidine), 5.49 (s, 1H, NH
pyrimidine), 2.51 (s, 2H, CH2); Anal. calcd. for C34H24N4O3S (568.31): C,
71.85; H, 4.22; N, 9.85; S, 5.63. Found: C, 71.69; H, 4.20; N, 9.81; S, 5.70.
3-Benzyl-2,2-diphenyl-7(H)-8-oxothiazolino[4,5:2ꢀ,3ꢀ]pyrano
[6ꢀ,5ꢀ-d]pyrimidine-9-spiro-3ꢀ-(1ꢀ-methylindolin-2ꢀ-one) (6b)
Yellowish brown crystals; yield (50%); m.p. 115–118◦C; IR: υ´ cm−1
3300 (NH), 1705 (C O), 1655 (C N); 1H NMR (DMSO-d6): δ 8.13–6.84
(m, 20H, Ar H and CH pyrimidine), 5.40 (s, 1H, NH pyrimidine), 3.39
(s, 3H, CH3), 2.51 (s, 2H, CH2); Anal. calcd. for C35H26N4O3S (582.32): C,
72.18; H, 4.46; N, 9.61; S, 5.49. Found: C, 72.04; H, 4.31; N, 9.56; S, 5.45.

New Spiropyranthiazoline Derivatives
2103
Synthesis of 3-Benzyl-2,2-diphenyl-7(H)-6-methyl-8-
oxothiazolino[4,5:2ꢀ,3ꢀ]pyrano [6ꢀ,5ꢀ-d]pyrimidine-9-
spiro-3ꢀ-(1ꢀ-methylindolin-2ꢀ-one) (7)
A solution of 5b (5.54 g, 10 mmol) in Ac2O/pyridine mixture (15 mL, 2/1
v/v) was heated in water bath for 4 h, then cooled to room temperature,
poured into an ice/water mixture, the formed solid product was col-
lected by filtration, washed several times with cold water, dried and re-
crystallized from ethanol to give dark brown crystals; yield (66%); m.p.
1
151–154◦C; IR: υ´ cm−1 3500 (NH), 1710 (C O), 1660 (C N); H NMR
(DMSO-d6): δ 8.21–6.85 (m, 19H, Ar H), 5.40 (s, 1H, NH), 3.39 (s, 3H,
CH3), 2.52 (s, 2H, CH2), 2.10 (s, 3H, CH3); Anal. calcd. for C36H28N4O3S
(596.33): C, 72.50; H, 4.69; N, 9.39; S, 5.36. Found: C, 72.30; H, 4.48; N,
9.25; S, 5.30.
Synthesis of Compounds 8a,b—General Procedure
A mixture of 5a or 5b (5 mmol) and formamide (10 mL) was heated
under reflux for 3 h. The reaction mixture was cooled, then poured
into an ice/water mixture, and the formed product filtered off, washed
several times by cold water, dried, and recrystallized from ethanol.
8-Amino-3-benzyl-2,2-diphenylthiazolino[4,5:2 ꢀ,3 ꢀ]pyrano
[6 ꢀ,5 ꢀ-d]pyrimidine-9-spiro-3 ꢀ-(indolin-2 ꢀ-ones) (8a)
Yellowish green crystals; yield (45%); m.p. 144–147◦C; IR: υ´ cm−1
3360–3210 (NH2), 3190 (NH), 1705 (C O), 1665 (C N); 1H NMR
(DMSO-d6): δ 10.21 (s, 1H, NH), 8.31-6.91 (m, 20H, Ar H and CH pyrim-
idine), 5.43 (s, 2H, NH2), 2.52 (s, 2H, CH2); Anal. calcd. for C34H25N5O2S
(567.32): C, 71.97; H, 4.40; N, 12.33; S, 5.64. Found: C, 71.86; H, 4.35;
N, 12.29; S, 5.52.
8-Amino-3-benzyl-2,2-diphenylthiazolino[4,5:2 ꢀ,3 ꢀ]pyrano
[6 ꢀ,5 ꢀ-d]pyrimidine-9-spiro-3 ꢀ-(1 ꢀ-methylindolin-2 ꢀ-one) (8b)
Green crystals; yield (43%); m.p. 151–154◦C; IR: υ´ cm−1 3360-3210
1
(NH2), 1705 (C O), 1660 (C N); H NMR (DMSO-d6): δ 8.40–6.85 (m,
20H, Ar H and CH pyrimidine), 5.02 (s, 2H, NH2), 3.51 (s, 3H, CH3),
2.51 (s, 2H, CH2); Anal. calcd. for C35H27N5O2S (581.33): C, 72.30; H,
4.64; N, 12.04; S, 5.50. Found: C, 72.23; H, 4.62; N, 11.91; S, 5.41.
Synthesis of Compounds 9a,b—General Procedure
A mixture of 5a or 5b (5 mmol) and malononitrile (0.33 g, 5 mmol) in
glacial acetic acid (10 mL) was heated under reflux for 4 h. The reaction
mixture was cooled to room temperature, and the formed solid product

2104
M. F. El-Zohry et al.
was filtered off, washed by cold water, dried, and recrystallized from
acetic acid.
8-Amino-3-benzyl-6-cyanomethyl-2,2-
diphenylthiazolino[4,5:2 ꢀ,3 ꢀ]pyrano[6 ꢀ,5 ꢀ-d]
pyrimidine-9-spiro-3 ꢀ-( indolin-2 ꢀ-one) (9a)
Bright brown crystals; yield (71%); m.p. 168–170◦C; IR: υ´ cm−1
3330–3210 (NH2), 3200 (NH), 2200 (CN), 1715 (C O); 1H NMR
(DMSO-d6): δ 9.92 (s, 1H, NH), 8.40 (s, 2H, NH2), 7.77–6.50 (m,
19H, Ar H), 3.99 (s, 2H, CH2), 2.51 (s, 2H, CH2); Anal. calcd. for
C36H26N6O2S (606.34): C, 71.30; H, 4.28; N, 13.85; S, 5.27. Found: C,
71.18; H, 4.27; N, 13.69; S, 5.19.
8-Amino-3-benzyl-6-cyanomethyl-2,2-
diphenylthiazolino[4,5:2 ꢀ,3 ꢀ]pyrano[6 ꢀ,5 ꢀ-d]
pyrimidine-9-spiro-3 ꢀ-(1 ꢀ-methyl indolin-2 ꢀ-one) (9b)
Red crystals; yield (70%); m.p. 160–163◦C; IR: υ´ cm−1 3320–3220
(NH2), 2200 (CN), 1710 (C O); 1H NMR (DMSO-d6): δ 8.39 (s, 2H, NH2),
7.71–6.50 (m, 19H, Ar H), 3.99 (s, 2H, CH2), 3.50 (s, 3H, CH3), 2.52 (s,
2H, CH2); Anal. calcd. for C37H28N6O2S (620.35): C, 71.63; H, 4.51; N,
13.54; S, 5.27. Found: C, 71.52; H, 4.42; N, 13.43; S, 5.06.
Synthesis of Compounds 11a,b—General Procedure
A solution of 5a or 5b (5 mmol) in pyridine (15 mL) and phenyliso-
cyanate (0.54 mL, 5 mmol) was heated under reflux for 5 h. After cool-
ing, the reaction mixture was poured into an ice/water mixture, the
formed product was collected by filtration, washed by cold water, dried,
and recrystallized from ethanol.
5(H)-3-benzyl-8-imino-6-oxo-2,2,7-
triphenylthiazolino[4,5:2 ꢀ,3 ꢀ]pyrano[6 ꢀ,5 ꢀ-d]
pyrimidine-9-spiro-3 ꢀ-(indolin-2 ꢀ-one) (11a)
Green crystals; yield (70%); m.p. 158–160◦C; IR: υ´ cm−1 3320 (NH),
3290 (NH), 1715 (C O); 1H NMR (DMSO-d6): δ 10.32 (s, 1H, NH), 9.75
(s, 1H, NH), 8.61 (s, 1H, NH), 7.85–6.42 (m, 24H, Ar H), 2.51 (s, 2H,
CH2); Anal. calcd. for C40H29N5O3S (659.37): C, 72.85; H, 4.39; N, 10.61;
S, 4.85. Found: C, 72.63; H, 4.38; N, 10.49; S, 4.71.
5(H)-3-Benzyl-8-imino-6-oxo-2,2,7-
triphenylthiazolino[4,5:2 ꢀ,3 ꢀ]pyrano[6 ꢀ,5 ꢀ-d]
pyrimidine-9-spiro-3 ꢀ-(1 ꢀ-methyl indolin-2 ꢀ-one) (11b)
Green crystals; yield (60%); m.p. 170–171◦C; IR: υ´ cm−1 3320 (NH),
1
3285 (NH), 1710 (C O); H NMR (DMSO-d6): δ 9.81 (s, 1H, NH), 8.62

New Spiropyranthiazoline Derivatives
2105
(s, 1H, NH), 7.85–6.43 (m, 24H, Ar H), 3.43 (s, 3H, CH3), 2.56 (s, 2H,
CH2); Anal. calcd. for C41H31N5O3S (673.38): C, 73.12; H, 4.60; N, 10.39;
S, 4.75. Found: C, 73.05; H, 4.50; N, 10.28; S, 4.71.
Synthesis of Compounds 12a,b—General Procedure
A mixture of 5a or 5b (10 mmol), triethyl orthoformate (10 mL), and
glacial acetic acid (2 mL) was heated under reflux for 5 h. The reaction
mixture was cooled then poured into an ice/water mixture with vigorous
stirring, the oily product thus formed was extracted by chloroform, dried
using anhydrous MgSO4 overnight, and filtered off. Then the solvent
was removed under reduced pressure, and the formed solid product was
collected by filtration and recrystallized from benzene.
3-Benzyl-6-cyano-2,2-diphenyl-5-ethoxymethiniminopyrano
[2,3-d]thiazoline-7-spiro-3 ꢀ-(indolin-2 ꢀ-ones) (12a)
Brown crystals; yield (60%); m.p. 125–127◦C; IR: υ´ cm−1 3200 (NH),
1
2200 (CN), 1705 (C O); H NMR (CDCl3): δ 10.35 (s, 1H, NH), 7.80–
6.80 (m, 19H, Ar H), 5.10 (s, 1H, CH), 3.95 (q, 2H, CH2), 2.52 (s, 2H,
CH2 benzylic), 1.52 (t, 3H, CH3); Anal. calcd. for C36H28N4O3S (596.33):
C, 72.50; H, 4.69; N, 9.39; S, 5.36. Found: C, 72.39; H, 4.85; N, 9.28; S,
5.29.
3-Benzyl-6-cyano-2,2-diphenyl-5-ethoxymethiniminopyrano
[2,3-d]thiazoline-7-spiro-3 ꢀ-(1’-methylindolin-2 ꢀ-ones) (12b)
Reddish brown crystals; yield (65%); m.p. 112–114◦C; IR: υ´ cm−1
2200 (CN), 1705 (C O); 1H NMR (CDCl3): δ 7.85–6.76 (m, 19H, Ar H),
5.15 (s, 1H, CH), 4.00 (q, 2H, CH2), 3.25 (s, 3H, CH3), 2.56 (s, 2H, CH2
benzylic), 1.05 (t, 3H, CH3); Anal. calcd. for C37H30N4O3S (610.34): C,
72.80; H, 4.91; N, 9.17; S, 5.24. Found: C, 72.62; H, 4.85; N, 9.16; S, 5.20.
Synthesis of Compounds 13a,b: General Procedure
A mixture of 5a or 5b (10 mmol) and hydrazine (5 mL, 80% ) in benzene
(15 mL) was heated in water bath for 2 h, cooled, the solvent was re-
moved under reduced pressure. The formed solid product was collected
by filtration washed by petroleum ether, dried and recrystallized from
ethanol.
7-Amino-3-benzyl-6-cyano-2,2-diphenyl-8-iminothiazolino
[4,5:2 ꢀ,3 ꢀ]pyrano[5 ꢀ,6 ꢀ-d]pyrimidine-9-spiro-3 ꢀ-
(indolin-2 ꢀ-ones) (13a)
Gray crystals; yield (50%); m.p. 140–143◦C; IR: υ´ cm−1 3310–3210
1
(NH2), 3190 (NH), 1705 (C O); H NMR (DMSO-d6): δ 10.40 (s, 1H,

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M. F. El-Zohry et al.
NH), 10.05 (s, 2H, NH2), 9.05 (s, 1H, NH), 7.94–6.40 (m, 20H, Ar H
and CH pyrimidine), 2.48 (s, 2H, CH2); Anal. calcd. for C34H26N6O2S
(582.32): C, 70.12; H, 4.46; N, 14.42; S, 5.49. Found: C, 70.01; H, 4.45;
N, 14.31; S, 5.40.
7-Amino-3-benzyl-6-cyano-2,2-diphenyl-8-imino-
thiazolidino[4,5:2 ꢀ,3 ꢀ]pyrano[5 ꢀ,6 ꢀ-d]pyrimidine
-9-spiro-3 ꢀ-(1 ꢀ-methylindolin-2 ꢀ-ones) (13b)
Green crystals; yield (45%); m.p. 134–136◦C; IR: υ´ cm−1 3310–3200
(NH2), 3190 (NH), 1705 (C O); 1H NMR (DMSO-d6): δ 9.95 (s, 2H, NH2),
9.00 (s, 1H, NH), 7.89–6.41 (m, 20H, Ar H and CH pyrimidine), 3.34
(s, 3H, CH3), 2.51 (s, 2H, CH2); Anal. calcd. for C35H28N6O2S (596.33):
C, 70.48; H, 4.69; N, 14.08; S, 5.36. Found: C, 70.38; H, 4.60; N, 14.00;
S, 5.27.
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