Selective Synthesis of 3-(α,α-Dibromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one as an Excellent Precursor for the Synthesis of 2-Substituted 4-(4-Hydroxy-6-methyl-2H-2-oxopyran-3-yl)thiazoles as Antimicrobial and Antifungal Agents

Article abstract of DOI:10.1002/jhet.3116

A selective synthesis of 3-(α,α-dibromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one (3) has been achieved by bromination of DHA using CuBr₂/CHCl₃-EtOAc. The reaction of 3 with different thioureas/thiomides/thiosemicarbazide offers a convenient and efficient method for the syntheses of 2-substituted 4-(4-hydroxy-6-methyl-2H-2-oxopyran-3-yl)thiazoles. These thiazoles were evaluated for their antimicrobial and antifungal activity.

Full text of DOI:10.1002/jhet.3116

Month 2018
Selective Synthesis of 3-(α,α-Dibromoacetyl)-4-hydroxy-6-methyl-2H-
pyran-2-one as an Excellent Precursor for the Synthesis of 2-Substituted
4-(4-Hydroxy-6-methyl-2H-2-oxopyran-3-yl)thiazoles as Antimicrobial
and Antifungal Agents
a
b
c
c
a
*
Jitander K. Kapoor, Richa Prakash, Ajay Kumar, Deepika Saini, and Loveena Arora
aDepartment of Chemistry, National Institute of Technology, Kurukshetra, India
bDepartment of Chemistry, Kurukshetra University, Kurukshetra, India
cInstitute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra, India
*
E-mail: loveena.arora22@gmail.com
Received September 18, 2017
DOI 10.1002/jhet.3116
Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com).
A selective synthesis of 3-(α,α-dibromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one (3) has been
achieved by bromination of DHA using CuBr2/CHCl3-EtOAc. The reaction of 3 with different
thioureas/thiomides/thiosemicarbazide offers a convenient and efficient method for the syntheses of
2-substituted 4-(4-hydroxy-6-methyl-2H-2-oxopyran-3-yl)thiazoles. These thiazoles were evaluated for
their antimicrobial and antifungal activity.
J. Heterocyclic Chem., 00, 00 (2018).
INTRODUCTION
The DHA molecule can exist in several tautomeric
forms, and structures of two important tautomers are
shown as 1 and la (Chart 1). Since DHA has several
reactive sites, the molecule is susceptible to the attack by
the nucleophilic and electrophilic reagents. A nucleophile
can, in principle, attack the carbonyl of C(3)-acetyl the
carbon atom terminating the conjugated carbon chain
6-position the lactone carbonyl at 2-position and the
carbon at position 4. On the other hand, an electrophile
can attack at positions 3,5,α-position of acetyl group, and
oxygen of C(4)-OH.
Because of availability of several reactive sites for
nucleophilic and elecrophilic attack, problems of
selectivity are generally encountered in the reactions of
DHA. For example, bromination of DHA gives different
brominated products depending upon the nature of
reagent and conditions [28–32] employed in the reaction.
The reported results are summarized in Chart 2.
In continuation of our interest in the use of DHA and its
derivatives as a versatile precursors for the synthesis of
various heterocyclic compounds, we became interested
in the synthesis of 2-substituted 4-(4-hydroxy-6-methyl-
2H-2-oxopyran-3-yl)thiazoles starting from DHA. In a
recent study by Hikam-Oukacha et al., [31] it has been
reported that such thiazoles can be synthesized by
the reaction of 3-(α-bromoacetyl)-4-hydroxy-6-methyl-2H-
pyran-2-one (2) with thioamides and related compounds
(Hantzsch thiazole synthesis, [33], Method I). In this report,
the authors have also addressed the problem related
to reproducibility of the results on bromination of DHA
using bromine under various conditions. They prepared
2-Pyrone and coumarin derivatives constitute an
exceptional class of heterocyclic compounds. They are
useful precursors for various compounds having diverse
biological properties, abundantly found in animals, insects,
plants, bacteria, and microbial systems [1–7]. They play a
key role in medicinal area and can be obtained by making
small changes in the substitution pattern on the 2-pyrone
ring. For instance, 4-hydroxy-2-pyrones are not only
considered as one of important classes of anti-HIV agents
but also exhibit a wide range of antifungal, phytotoxic,
antimicrobial, cytotoxic, and neurotoxic activities [8–10].
Another significant property found in 2-pyrone derivatives
is their potential in the treatment of Alzheimer’s and other
dementia diseases [11,12]. The most important and widely
studied 4-hydroxy-2-pyrone derivative is 3-acetyl-4-
hydroxy-6-methyl-2H-pyran-2-one (l, dehydro acetic acid,
abbreviated as DHA). This pyrone derivative has been
isolated from natural sources [13,14] and is also
industrially available utilizing a number of synthetic
procedures [15–18]. The reactions of DHA and its
derivatives have shown wide utility in organic syntheses
including various heterocyclic compounds [19–21]. DHA
is converted into 4-hydroxy-6-methyl-2H-pyran-2-one 2
(triacetic lactone) by the action sulfuric acid [8]. These
two natural occurring 2-pyrones have been extensively
studied as building blocks for
a wide range of
important biologically active heterocyclic compounds,
such as pyrimidines, pyridines, thiadiazoles, pyrazoles,
bipyrazoles, pyranopyrans, and benzodiazepines [22–27].
© 2018 Wiley Periodicals, Inc.

J. K. Kapoor, R. Prakash, A. Kumar, D. Saini, and L. Arora
Vol 000
Chart 1. Tautomers of DHA and reactive sites for a nucleophile
and an electrophile
Chart 2. Different brominated products under different reported conditions
α-bromoketone 2 in 61% yield by using bromine in acetic
acid under refluxing conditions [31].
such as sulfur nucleophile and bidentate nucleophiles
containing nitrogen and sulfur atoms [35–44]. These
studies involving α,α-dibromoketones have offered a
valuable modification to the most widely used Hantzsch
thiazoles synthesis [33]. Prompted by previous work
on the use of α,α-DBKs, we herein wish to report
our results on the selective synthesis of 3-(α,α-
dibromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one (3)
by using CuBr2/CHCl3-EtOAc [45] and its use as a
precursor in developing an efficient and convenient
synthesis of 2-substituted 4-(4-hydroxy-6-methyl-2H-2-
oxopyran-3-yl) thiazole (8).
Despite the fact that Hikam-Oukacha et al. [31]
succeeded in the selective bromination of DHA into 2
and then synthesis of thiazoles 8 by Method I, there
has been great demand to develop some alternative
approaches for such syntheses avoiding the use
molecular bromine and α-bromoketones [34] because of
several practical problems associated with them. In this
context, we and other research groups have earlier
shown that α,α-dibromketones behave analogous to α-
bromoketones in their reactions with certain nulceophiles
Scheme 1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Synthesis of 3-(α,α-dibromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one as an
Excellent Precursor for the Synthesis of 2-substituted 4-(4-Hydroxy-6-methyl-2H-
2-oxopyran-3-yl)thiazoles
Month 2018
Table 1
Table 2
Physical data of pyranylthiazoles.
x, y, z coordinates of grid box (PDB ID: 4EMV).
Sr. No
1
Compound
R
mp (°C)
Yield
90
center_x
center_y
center_z
size_x
size_y
size_z
23.045
32.231
0.769
40
40
40
8a
8b
8c
8d
240
235
250
220
2
3
4
70
66
74
various conditions has been reported for selective
α-monobromination and α,α-dibromination of DHA [32].
Based on our recent success on selective dibromination of
electron-rich ketones such as o/p-hydroxyacetophenones
by the method of King and Ostrum [45] involving
heterogeneous reagent system CuBr2/CHCl3-EtOAc, we
attempted bromination of DHA by this method.
Interestingly, after some experimentation with changing
reaction time and reagent, and monitoring the reaction
progress by scanning the H NMR of crude product at
different intervals, it was found that this method is most
suitable for effecting selective α,α-dibromination of
DHA. The desired bromoketone was available in high
yield without making the use of column chromatography
for purification.
5
6
7
8e
8f
200
148
240
67
70
60
l
8g
8
8h
─NHNH2
210
72
The structure of compound 3 was confirmed by the
comparison of mps and spectral data (1H NMR and
13C NMR) with those reported in literature. In particular,
1H NMR data were found to be most suitable for
monitoring the progress of reaction and identification of
the product. The most characteristic feature in the NMR
of 3 was appearance of singlets at δ 6.81 due to methine
(CHBr2) protons, respectively. The methyl protons (at δ
2.7) of acetyl group of DHA completely disappeared on
the formation of the brominated product.
RESULTS AND DISCUSSION
Chemistry. Selective bromination of DHA with CuBr2/
CHCl3-EtOAc.
First, we focused our attention to
develop a new method eliminating the use of bromine
for the synthesis of α,α-dibromoketone 3. To the best of
our knowledge, among the various reagents, which
avoid the use of bromine and have been used for selective
bromination of other ketones. Only one reagent
system, that is, NBS in combination with p-TsOH under
The results of the present study using CuBr2/CHCl3-
EtOAc offer a new method for selective high yield α,α-
dibromination of DHA [46]. The method is superior to
Scheme 2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

J. K. Kapoor, R. Prakash, A. Kumar, D. Saini, and L. Arora
Vol 000
Table 3
pMIC (μmol/mL) values of all the compounds and standard drugs against bacterial and fungal strains.
Bacterial strains (pMIC μmol/mL)
Gram positive
Gram negative
Fungal strains (pMIC μmol/mL)
Staphylococcus
aureus
Bacillus
subtilis
Staphylococcus
epidermidis
Escherichia
Pseudomonas
aeruginosa
Candida
albicans
Aspergillus
niger
Compound
coli
8a
8b
8c
8d
8e
8f
8g
8h
1.38
1.4
1.38
1.4
1.38
1.4
1.38
1.4
1.38
1.4
1.982
2.002
2.029
1.723
2.043
1.658
1.643
1.582
—
1.982
1.099
1.427
1.422
2.043
1.357
1.342
1.281
—
1.427
1.422
1.441
1.357
1.342
1.281
3.042
3.080
—
1.728
1.422
2.043
1.357
1.342
1.281
3.042
3.080
—
1.427
1.422
1.441
1.357
1.342
1.281
3.042
3.080
—
1.427
1.422
1.441
1.357
1.342
1.281
3.042
3.080
—
1.427
1.422
1.441
1.357
1.342
1.281
3.042
3.080
—
Ciprofloxacin
Ofloxacin
Fluconazole
—
3.008
—
3.008
Table 4
Binding affinity and binding mode of ligands with receptor (PDB ID: 4EMV).
Compound
Dock score
Number of hydrogen bonds
Amino acids involved in H-bonding
Distance (A°)
8a
8b
8c
8d
8e
8f
8g
8h
ꢀ6.8
ꢀ7.1
ꢀ7.2
ꢀ7.2
ꢀ7.6
ꢀ6.8
ꢀ6.3
ꢀ5.7
ꢀ6.3
ꢀ6.1
—
1
1
1
1
—
—
1
1
2
—
—
THR100
THR100
THR100
LYS154
—
3.107
2.984
2.112
2.233
—
—
—
SER 58
LYS154
SER58
ARG81
2.093
1.982
2.017
2.079
Ciprofloxacin
Fluconazole
Figure 1. Docking interaction of compound 8e with microbial receptor (PDB ID: 4EMV) showing hydrogen bond in green line. [Color figure can be
viewed at wileyonlinelibrary.com]
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Synthesis of 3-(α,α-dibromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one as an
Excellent Precursor for the Synthesis of 2-substituted 4-(4-Hydroxy-6-methyl-2H-
2-oxopyran-3-yl)thiazoles
Month 2018
Figure 2. Docking interaction of ciprofloxacin with microbial receptor (PDB ID: 4EMV) showing hydrogen bond in green line. [Color figure can be
viewed at wileyonlinelibrary.com]
Figure 3. Docking interaction of fluconazole with microbial receptor (PDB ID: 4EMV) showing hydrogen bond in green line. [Color figure can be
viewed at wileyonlinelibrary.com]
the reported methods for bromination of ketones in terms
of selectivity of the reaction, operational simplicity of the
procedure involved, avoiding the use of bromine and dry
conditions.
ethanol by stirring the equimolar mixture of the reactants at
room temperature. The reaction occurred according to the
expectation with the formation of 8a as a yellow solid
within 5–10 min. This was an encouraging observation as
the desired product was isolated simply by filtration in
~90% yield and almost in pure state without further
purification. The other nucleophilic reactants also reacted
with 3 in a similar manner to afford the desired thiazoles in
high yields (Scheme 1, Table 1).
A comparison of our results (Method II) with the recently
reported compounds involving α-bromoketone 2 (Method I)
clearly indicates that Method II is superior in terms of
operational simplicity, yields, time, and temperature
required for reaction. While studying the scope of present
study on the new examples, it was found that the reaction
of 305-dimethylpyrazole-1-thiocarboxamide is particularly
noteworthy. In this case the reaction with 3 (Method II)
Synthesis of 2-substituted 4-(4-hydroxy-6-methyl-2H-2-
oxopyran-3-yl)thiazoles (8) (Method II).
As mentioned
earlier, DBKs can offer a superior altenative to the highly
lachrymatory BKs, which are extremely useful precursors
in the Hantzsch reaction for thiazoles synthesis. The DBks-
based Hantzsch modification has also provided an efficient
synthesis of bromopyranylthiazoles [27,28]. Delighted by
this observation, we investigated the reactivity of 3-(α,α-
dibromoacetyl-4-hydroxy-6-methyl-2H-pyran-2-one (3)
toward some thioamides, thioureas, thiosemicarbazide, and
thiosemicarbazoes with the hope of obtaining the
corresponding 2-substituted pyranylthiazoles. Initially, we
attempted the reaction of 3 with N-phenylthiourea in
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

J. K. Kapoor, R. Prakash, A. Kumar, D. Saini, and L. Arora
Vol 000
occurred smoothly at room temperature with the formation
of desired thiazole derivative 8, whereas the reaction with
2 (Method I) gave a mixture of 3,5-dimethylpyrazole and
α-thiocyanatoketone rather than the expected thiazole 8.
The harsh reaction condition (refluxing for long time),
involved in Method I probably led to decomposition
of thiocarboxamide with the generation of 3,5-
dimethylpyrazole and α-thiocyanatoketone, formed by the
antifungal activity. The minimum concentration of each
compound that prevented visible growth of microbes was
considered as minimal inhibitory concentration.
Docking studies. The molecular docking study of the
series was performed using AutoDockVina program [49],
and the 2D structure of all the ligand molecules was
prepared in MarvinSketch 6.2.2 (ChemAxon, Budapest,
Hungary) and then converted into 3D for energy
minimization and saved in pdbqt format using AutoDock
Tools 1.5.6. The crystal structure of 4EMV was retrieved
from protein data bank (www.rcsb.org) for docking
simulations [50]. As protein preparation, the water of
crystallization was removed and polar hydrogens were
added. In AutoDockVina, the active binding cavity was
generated as grid box with specific parameters given in
Table 2. Docked structures were visualized using
PyMOL, and the results were analyzed to obtain
familiar with the interaction of ligand molecules with
receptor [51].
nucleophilic substitution of
2 with insitu-generated
thiocyanate (Scheme 2). Obviously, the present method
involving dibromoketone with milder conditions is of
wider application. The thiazole derivatives synthesized in
this work may find applications as biologically active
compounds.
CONCLUSIONS
In summary, we report herein selectively synthesized
3-(α,α-dibromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one
(3) using CuBr2/CHCl3-EtOAc. This study provides the
cleanest method for preparation of 3, which is an excellent
precursor for the synthesis of 2-substituted 4-(4-hydroxy-6-
methyl-2H-2-oxopyran-3-yl)thiazoles of great biological
importance.
Antimicrobial activity.
The synthesized compounds
were evaluated for their in vitro antibacterial activity
against pathogenic strains including Gram-positive
bacteria (S. aureus, B. subtilis, and S. epidermidis) and
Gram-negative bacterial strains (P. aeruginosa and
E. coli). The compounds were also screened against fungal
strains, C. albicans and A. niger. pMIC calculated from
MIC was considered for the evaluation of antimicrobial
study, and values for each compound and standard drugs
as well have been provided in Table 3 against all strains of
bacteria and fungus.
Compound 8e displayed maximum value of pMIC
against all the strains of microorganisms and found to be
most potent compound among the series. It is clearly
indicated that the presence of electron-withdrawing group
(─NO2) led to the development of most active scaffold.
Compound 8c, halogen substituted, was also found to be
almost equally potent against bacterial strain. Compound
8h was found to be least active among the series and
revealed that the absence of aromatic ring next to thiazole
ring decreased the activity.
One more interesting finding displayed by 8a is
unsubstituted aromatic ring that the compound was not
possessing activity against any strain of bacterial while
having good potency against fungal strain. This might
help us to synthesize drugs having specific action against
fungal infection. The interaction of compounds with the
receptor molecule is further studied with the help of
molecular docking.
Docking study. In the docking study, all the synthesized
compounds were docked into the cavity of receptor (PDB
ID: 4EMV) using AutoDockVina. The present molecular
docking study provided a significant insight into ligand-
receptor binding as well as binding mode. The binding
energy and pattern of the ligands with protein is provided
Biological screening. Antimicrobial activity.
The
synthesized compounds were evaluated for their in vitro
antimicrobial activity against bacterial (both Gram
positive and Gram negative) and fungal strains by using
serial dilution technique to find their minimum inhibitory
concentration [47]. The nutrient media were prepared by
dissolving weighed amount of nutrient broth and
sabouraud dextrose broth in distilled water for bacteria
and fungus respectively and 1 mL of nutrient medium
will be transferred to each test tube; 0.01 g of synthesized
drug sample was dissolved in 10 mL of dry DMSO to
give a stock solution of 100 μg/mL. The solution of test
compounds was transferred to test tubes having sterilized
nutrient medium to obtain a set of five dilutions of test
compounds having concentrations 50, 25, 12.5, 6.25, and
3.125 μg/mL. Minimal inhibitory concentration for each
sample was investigated against three Gram-positive
bacterial strains, Staphylococcus aureus (MTCC 7443),
Bacillus subtilis (MTCC 441), and Staphylococcus
epidermidis (MTCC 6880); against two Gram-negative
bacterial strains, Pseudomonas aeruginosa (MTCC 424)
and Escherichia coli (MTCC 1652); and two fungal
strains, Candida albicans (MTCC 227) and Aspergillus
niger (MTCC 8189). The freshly cultured strains of each
organism were transferred into test tubes and incubated at
37
1°C for 24 h for bacterial strains, 48 h for
C. albicans and 7 days at 25 1°C for A. niger [48].
Ciprofloxacin and ofloxacin were considered as reference
standard for antibacterial activity and fluconazole for
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Synthesis of 3-(α,α-dibromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one as an
Excellent Precursor for the Synthesis of 2-substituted 4-(4-Hydroxy-6-methyl-2H-
2-oxopyran-3-yl)thiazoles
Month 2018
in Table 4. The result clearly indicated that the compound
8e should possess the maximum potency against
microbes as the binding energy was calculated as
ꢀ7.6 kcal/mol, best dock score among the series. The
interacting residues notable for binding are THR100,
SER58, LYS154, and ARG81. The interaction of
compound 8e, ciprofloxacin, and fluconazole via
hydrogen bonding has been shown in Figures 1–3,
respectively.
3H, ─CH3), 7.34–7.50 (m, 5H, Ar), 6.2 (s, 1H, pyrone),
7.2 (s, 1H, thiazole). 13C NMR (DMSO-d6): 19.4
(─CH3), 24.3 (3 ─CH3), 101.1(thiazole), 101.9 (aromatic
ring), 159 (thiazole), 160 (carbonyl, C═O).
4-(4-Hydroxy-6-methyl-2-pyran-3-yl)-2-amino-(-40-methyl)
phenylthiazole (8b). Yellow solid. IR (νmax, cmꢀ1, KBr):
1
3100–3500 cmꢀ1, 1704 cmꢀ1. H NMR (DMSO-d6) δ:
1.98 (s, 3H, CH3), 2.35(s, 3H, ─CH3), 7.0–7.5(m, 4H),
6.2 (s, 1H, pyrone), 5.5 (s, 1H, thiazole). 13C NMR
(DMSO-d6): 19.4 (3 ─CH3), 24.3 (3 ─CH3),
101.1(thiazole), 101.9 (aromatic ring), 159 (thiazole), 160
(carbonyl, C═O). MS (ES+): m/z M+ (315).
EXPERIMENTAL
4-(4-Hydroxy-6-methyl-2-pyran-3-yl)-2-amino-(-40-chloro)
phenylthiazole (8c). Yellow solid. IR (νmax, cmꢀ1, KBr):
Melting points were taken in open capillaries and are
uncorrected. 1H NMR spectra were recorded on a Brucker
400 MHz instrument using TMS as an internal standard.
IR spectra were recorded on a Perkin-Elmer 1800 IR
spectrophotometer. Most of the common chemicals such
as dehydroacetic acid, bromine, and CuBr2 were obtained
from commercial suppliers.
1
3100–3500 cmꢀ1, 1701 cmꢀ1. H NMR (DMSO-d6) δ:
2.4(s, 3H, ─CH3), 7.34–7.50 (m, 4H), 6.2 (s, 1H,
pyrone), 6.4 (s, 1H, thiazole). 13C NMR (DMSO-d6):
19.4 (─CH3), 24.3 (3 ─CH3), 101.1(thiazole), 101.9
(aromatic ring), 159 (thiazole), 160 (carbonyl, C═O). MS
(ES+): m/z M+ (335), M+ +2 (337).
4-(4-Hydroxy-6-methyl-2-pyran-3-yl)-2-amino-(-40-methoxy)
phenylthiazole (8d). Yellow solid. IR (νmax, cmꢀ1, KBr):
3-(α,α-Dibromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-
1
1704 cmꢀ1. H NMR (DMSO-d6) δ: 2.30 (s, 3H, CH3),
one (3).
The copper(II) bromide was finely ground,
without drying, in a mortar and pestle to ensure large
surface area for reaction. Copper(II) bromide (0.05 mole)
was placed in a conical flask fitted with a reflux condenser,
and ethyl acetate (25 mL) was added. To the resulting
suspension was added the solution of DHA (1,
0.03 mole) in hot chloroform (25 mL). The reaction
mixture was refluxed with vigorous stirring until the
reaction was complete within 10 h, as judged by color
change of the solution from green to amber,
disappearance of all black solid, and cessation of
hydrogen bromide evolution and TLC of the crude
product. The reaction mixture was allowed to cool to
room temperature, and thus, the resulted solid Cu(I)Br
was removed by filtration. The filtrate was washed
with aqueous sodium metabisulphite solution, and
solvents were removed from the filtrate under reduced
pressure to give the desired α,α-dibromo DHA (3).
3.8 (s, 3H, OCH3), 7.24–7.38 (m, 4H, Ar), 6.2 (s, 1H,
pyrone), 7.4(s, 1H, thiazole). 13C NMR (DMSO-d6): 20
(3 ─CH3), 55(3C, OCH3), 101.1(thiazole), 101.9
(aromatic ring), 168(C═O).
4-(4-Hydroxy-6-methyl-2-pyran-3-yl)-2-amino-(-40-nitro)
phenylthiazole (8e). Yellow solid. IR (νmax, cmꢀ1, KBr):
1
3100–3500 cmꢀ1, 1700 cmꢀ1. H NMR (DMSO-d6) δ:
2.39 (s, 3H, CH3), 7.5–8.5(m, 4H), 6.2 (s, 1H, pyrone),
5.5 (s, 1H, thiazole).
13C NMR (DMSO-d6): 19.4 (3 ─CH3), 101.1(thiazole),
101.9 (aromatic ring), 143 (thiazole), 168 (carbonyl, C═O).
4-(4-Hydroxy-6-methyl-2-pyran-3-yl)-2-phenylthiazole
(8f).
Yellow solid. IR (νmax, cmꢀ1, KBr): 3100–
3500 cmꢀ1, 1703 cmꢀ1. H NMR (DMSO-d6) δ: 2.50
(s, 3H, CH3), 7.49–7.91 (m, 5H, Ar), 6.2 (s, 1H,
pyrone), 7.4(s, 1H, thiazole). 13C NMR (DMSO-d6):
21 (3 ─CH3), 101.1(thiazole), 101.9 (aromatic ring),
1
168(C═O).
mp 88–89°C (lit mp 88–89°C; yield 85%), IR (νmax
,
4-(4-Hydroxy-6-methyl-2-pyran-3-yl)-2-(3,4-
cmꢀ1, KBr): 3400, 1730, 1630, 1570, 1H NMR(CDCI3,
dimethylpyrazolylthiazole (8g).
Dark yellow solid. IR
(νmax, cmꢀ1, KBr): 3100–3500 cmꢀ1, 1700 cmꢀ1 1H
.
δ ): 2.4 (s, 3H), 7.4(s, 1H), 6.04 (s, 1H).
General procedure for the synthesis of 2-substituted 4-(4-
NMR (DMSO-d6) δ: 2.40 (s, 3H, CH3), 2.79 (s, 3H,
─CH3), 2.05 (s, 3H, ─CH3), 4.99 (s, 2H, ─CH2), 6.2 (s,
1H, pyrone), 7.1(s, 1H, thiazole), 7.23 (1H pyrazole). 13C
NMR (DMSO-d6): 20 (3 ─CH3), 55(3C, OCH3),
101.1(thiazole), 101.9 (aromatic ring), 134(pyrazol), 143
hydroxy-6-methyl-2H-2-oxopyran-3-yl)thiazoles.
To the
solution of (2 mmol, 3) in ethanol (10 mL) was added
thioamide or thiourea or thiosemicarbazone (2 mmol),
and the mixture (solution or suspension) was allowed
to stir at room temperature. After about 10 min, a
solid separated out, which was recrystallized from
ethanol. Spectral and analytical data of the products
are as follows.
(thiazole), 168 (carbonyl, C═O).
4-(4-Hydroxy-6-methyl-2-pyran-3-yl)-2-hydrazinylthiazole
(8h).
Yellow solid. IR (νmax, cmꢀ1, KBr): 3100–
3500 cmꢀ1, 1754 cmꢀ1. H NMR (DMSO-d6) δ: 2.23 (s,
3H, CH3), 6.2 (s, 1H, pyrone), 7.43(s, 1H, thiazole). 13C
NMR (DMSO-d6): 19.4 (3 ─CH3), 101.1(thiazole), 101.9
(aromatic ring), 143 (thiazole), 168 (carbonyl, C═O).
1
4-(4-Hydroxy-6-methyl-2-pyran-3-yl)-2-aminophenylthiazole
(8a).
Yellow solid. IR (νmax, cmꢀ1, KBr): 3100–
1
3500 cmꢀ1, 1703 cmꢀ1. H NMR (DMSO-d6) δ: 2.44(s,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

J. K. Kapoor, R. Prakash, A. Kumar, D. Saini, and L. Arora
Vol 000
[31] Hikem-Oukacha, D.; Rachedi, Y.; Hamdi, M.; Silva, A. M. S. J
Heterocyclic Chem 2011, 48, 31.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet