A facile one-step synthesis of new types of 8-thiazolyl and 8-thiadiazinyl coumarins

Article abstract of DOI:10.1080/10426500802274104

N-[4-(7-Methoxy-4-methyl-2-oxo-2H-chromen-8-yl)-thiazol-2-yl]-guanidine (2) has been prepared by the condensation of 4-methyl-7-methoxy-8-(2-bromoacetyl) coumarin (1) with guanylthiourea. 4-Methyl-7-methoxy-8-[2-(N'-(1-phenyl- ethylideneisopropylidene)-hy

Full text of DOI:10.1080/10426500802274104

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Phosphorus, Sulfur, and Silicon
and the Related Elements
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A Facile One-Step Synthesis of
New Types of 8-Thiazolyl and
8-Thiadiazinyl Coumarins
V. Rajeswar Rao a & K. M. Reddy a
a Department of Chemistry, National Institute of
Technology, Warangal, India
Published online: 19 Feb 2009.
To cite this article: V. Rajeswar Rao & K. M. Reddy (2009) A Facile One-Step Synthesis
of New Types of 8-Thiazolyl and 8-Thiadiazinyl Coumarins, Phosphorus, Sulfur, and
Silicon and the Related Elements, 184:3, 743-752, DOI: 10.1080/10426500802274104
To link to this article: http://dx.doi.org/10.1080/10426500802274104
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Phosphorus, Sulfur, and Silicon, 184:743–752, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802274104
A Facile One-Step Synthesis of New Types of 8-Thiazolyl
and 8-Thiadiazinyl Coumarins
V. Rajeswar Rao and K. M. Reddy
Department of Chemistry, National Institute of Technology, Warangal,
India
N-[4-(7-Methoxy-4-methyl-2-oxo-2H-chromen-8-yl)-thiazol-2-yl]-guanidine (2) has
been prepared by the condensation of 4-methyl-7-methoxy-8-(2-bromoa-
cetyl)coumarin (1) with guanylthiourea. 4-Methyl-7-methoxy-8-[2-(Nꢀ-(1-phenyl-
ethylideneisopropylidene)-hydrazino]-thiazol-4-yl]chromen-2-ones (3, 4, and 5)
have been prepared by reaction of 4-methyl-7-methoxy-8-(2-bromoacetyl)
coumarin (1) and thiosemicarbazide in presence of acetophenone or ace-
tone without any solvent. The formation of these compounds was further
confirmed by the condensation of acetophenone/acetone thiosemicarbazones
with 4-methyl-7-methoxy-8-(2-bromoacetyl)coumarin (1) in anhydrous ethanol
in a two-step process. Similarly 8-[2-[Nꢀ-(benzylidene)hydrazine]-thiazol-4-yl]-
7-methoxy-4-methyl-chromen-2-ones (6, 7, and 8) have been prepared by
the condensation of 4-methyl-7-methoxy-8-(2-bromoacetyl)chromen-2-one with
thiosemicarbazide and various aromatic aldehydes in a single step without any sol-
vent. The formation of these compounds was further confirmed by the condensation
of appropriately substituted benzaldehyde thiosemicarbazones with 4-methyl-7-
methoxy-8-(2-bromoacetyl)coumarin in anhydrous ethanol. 4-Methyl-7-methoxy-
8-(2-bromoacetyl) chromen-2-one (1) upon condensation with 3,5-dimercapto-
4-amino-s-triazole in anhydrous ethanol resulted in the formation of 8-(3-
mercapto-3H-[1,2,4]triazolo[3,4-b]thiadiazin-6-yl)-7-methoxy-4-methyl chromen-2-
one (9). This compound (9) on reaction with various alkyl and phenacyl halides in
anhydrous ethanol gave corresponding 4-methyl-7-methoxy-8-[3-(2-oxo-substituted
sulphanyl)-7H-[1,2,4]triazolo[3,4-b]thiadiazin-6-yl]chromen-2-ones (10 to 18). The
structures of newly prepared compounds have been confirmed from analytical and
spectral data.
Keywords Coumarin; thiadiazine; thiadiazole; thiazolyl coumarin
Received 31 December 2007; accepted 16 June 2008.
The authors are grateful to the Director, IICT, Hyderabad, and CDRI, Lucknow, for
providing spectral data. The authors are also thankful to the Director, NIT, Warangal,
for providing the facilities.
Address correspondence to V. Rajeswar Rao, Department of Chemistry, National In-
stitute of Technology, Warangal 506 004, India. E-mail: vrajesw@yahoo.com
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V. R. Rao and K. M. Reddy
INTRODUCTION
A coumarin ring is found in a variety of natural products, which ex-
hibit various pharmacological effects. Derivatives of coumarin are also
important in drugs having varied properties. There are excellent mono-
graphs and review articles1−5 describing the structure, synthetic reac-
tions, and properties of coumarins. Numerous reports have appeared
in the literature that describe antimicrobial,6,7 antiradiation,8,9 and
antiparasitic10 properties of the thiazole ring. Various 1,2,4-triazoles
and N-bridged heterocycles derived from them are found to be associ-
ated with diverse pharmacological activities.11−16
SCHEME 1
Prompted by the above observations, and in continuation of
our search for biologically active nitrogen- and sulfur-containing
heterocycles,17−20 we decided to synthesize these heterocyclic
coumarins.
RESULTS AND DISCUSSION
Synthesis of N-[4-(7-methoxy-4-methyl-2-oxo-2H-chromen-8-yl)-thia-
zolo-2-yl]-guanidine (2) has been achieved by the condensation of 4-
methyl-7-methoxy-8-(2-bromoacetyl)coumarin (1) with guanylthiourea

New Types of 8-Thiazolyl and 8-Thiadiazinyl Coumarins
745
in
anhydrous
ethanol.
4-Methyl-7-methoxy-8-[2-(Nꢀ-(1-phenyl-
ethylidene/isopropylidine)hydrazino]thiazol-4-yl]chromen-2-ones
(3, 4, and 5) have been obtained by the reaction of 4-methyl-7-methoxy-
8-(2-bromoacetyl)coumarin (1) thiosemicarbazide, acetophenones, and
acetone in a single step under solvent free conditions. Alternatively,
these compounds were synthesized in a two-step process involving
condensation of thiosemicarbazones, acetophenones, and acetone with
1 in anhydrous ethanol. Similarly, condensation of 1 with thiosemicar-
bazide and appropriately substituted aromatic aldehydes in a single
step gave the corresponding thiazoles (6, 7, and 8). The structures
of these compounds were further confirmed by the condensation of
1 with aromatic aldehyde thiosemicarbazones in anhydrous ethanol.
This is a two step process. The compounds obtained by both methods
are identical (by mixed mp measurements, TLC, and IR spectra).
All the hydrazino thiazolyl coumarins (3–8) displayed characteristic
absorption bands due to –C=N and lactone –C=O at 1611 and
1738 cm−1. The 1H NMR spectra of 5 exhibited a characteristic
singlet for thiazole and coumarin C3-protons at δ 7.68 and 6.15,
respectively. The remaining protons are observed in the usual region
(Table I).
The 8-(3-mercapto-7H-[1,2,4]triazolo[3,4-b]thiadiazin-6-yl)-7-meth-
oxy-4-methyl chromen-2-one (9) was synthesized by condens-
ing 3,5-dimercapto-4-amino-s-triazole with 4-methyl-7-methoxy-8-(2-
bromoacetyl)chromen-2-one in anhydrous ethanol. The compound
(9) upon condensation with various alkyl and phenacyl halides
in anhydrous ethanol gave corresponding 4-methyl-7-methoxy-8-
[3-(2-oxo substituted sulphanyl)-7H-[1,2,4]triazolo[3,4-b]thiadiazin-6-
yl]chromen-2-ones (10–18). All the compounds displayed strong ab-
sorption bands due to –C=N- and lactone carbonyl of coumarin at
1603–1615 and 1726–1738. The 1H NMR spectrum of 14 exhibited
a characteristic singlet for –S-CH2 of thiadiazine at δ 3.9. The –CH2-S-
appeared as singlet at δ 4.9. The remaining protons were observed in
the expected region (Table I).
EXPERIMENTAL
All melting points were determined in open capillary tubes using a
sulfuric acid bath and were uncorrected. IR spectra (ν max, cm−1) were
1
recorded on a Perkin Elmer instrument. The H NMR spectra were
recorded on a Varian 200 MHz spectrometer using tetramethyl silane
(TMS) as internal standard. Chemical shift values are expressed δ ppm.
Mass spectra were scanned on Perkin-Elmer, SCIEX-API-2000, ESI,

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750
V. R. Rao and K. M. Reddy
12.5 eV. The purity of the compounds was monitored by TLC performed
on silica gel plates (Merck) using benzene:acetone (3:1) solvent.
The 3,5-dimercapto-4-amino-s-triazole21 and 4-methyl-7- methoxy-
8-(2-bromoacetyl)coumarin22 were prepared according to the literature.
Synthesis of N-[4-(7-Methoxy-4-methyl-2-oxo-2H-chromen
-8-yl)-thiazol-2-yl]guanidine (2)
A mixture of 4-methyl-7-methoxy-8-(2-bromo acetyl)chromen-2-one
(0.311 g, 0.01 mol) and guanylthiourea (0.103 g, 0.01 mol) in anhydrous
ethanol (10 mL) was refluxed for 1 h. The reaction mixture was cooled
at room temperature. The solid that separated was filtered, dried, and
recrystallized from methanol.
Synthesis of 4-Methyl-7-methoxy-8-[N’-(1-phenyl
ethylidene/isopropylidene)-hydrazinothiazol-4-yl]chromen
-2-ones (Method 1) (3, 4, 5)
A mixture of 4-methyl-7-methoxy-8-(2-bromo-acetyl-chromen-2-one
(0.311 g, 0.01 mol), thiosemicarbazide (0.91 g, 0.01 mol), and acetophe-
none (0.01 mol) or acetone (0.01 mol) in anhydrous ethanol (10 mL) was
refluxed for 0.5 h. The reaction mixture was cooled at room tempera-
ture. The solid that separated was filtered, dried, and recrystallized
from methanol.
Alternative Synthesis of 4-Methyl-7-methoxy-8-(N’-1-phenyl
ethylidene/isopropylidene)hydrazinothiazol-4-yl]chromen
-2-ones (Method 2)
A mixture of acetophenone or acetone thiosemicarbazone (0.193 g,
0.01 mol) and 4-methyl-7-methoxy-8-(2-bromoacetyl-chromen-2-one
(0.311 g, 0.01 mol) was refluxed in anhydrous ethanol for 30 min. The
resulting solid was filtered and recrystallized from a suitable solvent.
8-[2-[N’-(Benzylidene)hydrazine)thiazol-4-yl]-7-methoxy
-4-methylchromen-2-ones (Method 1) (6, 7, and 8)
A mixture of 4-methyl-7-methoxy-8-(2-bromo acetyl)chromen-2-one
(0.311 g, 0.01 mol), thiosemicarbazide (0.91 g, 0.01 mol), and the ap-
propriate aromatic aldehyde (0.01 mol) in anhydrous ethanol was re-
fluxed for 0.5 h. The reaction mixture was cooled at room temperature.

New Types of 8-Thiazolyl and 8-Thiadiazinyl Coumarins
751
The solid that separated was filtered, dried, and recrystallized from
methanol.
Alternative Synthesis of
8-[2-(N’-(Benzylidene)hydrazine)thiazol-4-yl]-7-methoxy-4
-methylchromen-2-ones (Method 2)
A mixture of 4-methyl-7-methoxy-8-(2-bromoacetyl)chromen-2-one
(0.311 g, 0.01 mol) and thiosemicarbazone of the appropriate aromatic
aldehyde (0.01 mol) was refluxed in anhydrous ethanol for 30 min. The
resulting solid was filtered and recrystallized from a suitable solvent.
8-(3-Mercapto-3H-[1,2,4]triazolo[3,4-b]thiadiazin-6-yl)
-7-methoxy-4-methylchromen-2-one (9)
A mixture of 4-methyl-7-methoxy-8-(2-bromoacetyl)chromen-2-one
(0.311 g, 0.01 mol) and 2,5-dimercapto-4-amino-1,2,4-triazole (0.148 g,
0.01 mol) was taken in 10 mL of anhydrous ethanol, which was heated
to reflux over a period of 3–4 h. Upon cooling at room temperature, the
solid separated was filtered, dried, and recrystallized from methanol.
4-Methyl-7-methoxy-8-[3-(2-oxo substituted sulphanyl)
-7H-[1,2,4]-triazolo[3,4-b]thiadiazin-6-yl]chromen-2-ones
(10–18)
A mixture of 8-(3-mercapto-7H-[1,2,4]triazolo[3,4-b]1,3,4]thiadiazin-6-
yl)-methoxy-4-methyl-chromen-2-one (0.360 g, 0.01 mol) and phenacyl
bromide (0.01 mol) or the appropriate alkyl halide or acylhalide (0.01
mol) was taken of anhydrous ethanol (10 mL), which was heated to
reflux over a period of 4 h Upon cooling at room temperature, the solid
that separated was filtered, dried, and recrystallized from methanol.
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