Microwave assisted efficient synthesis of imidazole-based privileged structures

Article abstract of DOI:10.1021/cc900152y

A simple and efficient microwave assisted synthesis of imidazobenzoxazines, imidazobenzoxazin-5-ones, and imidazobenzoxazin-5-thiones with broad chemistry scope is described. The molecules were prepared both under conventional, as well as microwave heating conditions, to provide in high yields with clean and scalable reactions a small library of imidazole-based privileged structures for drug discovery.

Full text of DOI:10.1021/cc900152y

J. Comb. Chem. 2010, 12, 181–185
181
Microwave Assisted Efficient Synthesis of Imidazole-Based Privileged
Structures
Marco Fantini, Valentina Zuliani, Mario A. Spotti, and Mirko Rivara*
Dipartimento Farmaceutico, UniVersita` degli Studi di Parma, V.le G.P. Usberti, 27/A,
I-43124 Parma, Italy
ReceiVed September 28, 2009
A simple and efficient microwave assisted synthesis of imidazobenzoxazines, imidazobenzoxazin-5-ones,
and imidazobenzoxazin-5-thiones with broad chemistry scope is described. The molecules were prepared
both under conventional as well as microwave heating conditions, to provide in high yields with clean and
scalable reactions a small library of imidazole-based privileged structures for drug discovery.
Introduction
previously published one-pot solution-phase synthesis
methodology.17–19 This efficient synthetic route was here
exploited in the preparation of a series of substituted
imidazoles (1-6, Scheme 1), a starting point to obtain new
N-containing polycyclic structures (7a-n, Scheme 2). The
imidazoles 4-6 were cyclized to prepare various imida-
zobenzoxazines, characterized by the presence of three
different sites of structural variation, developing a protocol
for parallel synthetic application using simple experimental
conditions and avoiding purification steps. Moreover, we
synthesized these new polycyclic heterocycles using both
conventional solution-phase synthesis and microwave ir-
radiation, with the aim to propose a comparison between
these two techniques and to develop a rapid and scalable
process.
In the last years, there is growing interest in designing
and synthesizing new chemical libraries based on privileged
structures, especially focusing on heterocyclic structures, that
belong to a class of compounds with proven utility in
medicinal chemistry.1–3 The term “privileged structure” was
introduced by Evans et al. as a single molecular framework
able to provide ligands for diverse receptors.4 Since then,
many substructural frameworks have been described as
privileged structures and, in particular, N-containing poly-
cyclic structures have been reported to be associated with a
wide range of biological activity.1,5–9 There are almost
unlimited combinations of annulated heterocyclic structures
that can be designed with the aim to obtain polycyclic
skeletons with diverse physical, chemical, and biological
properties and with a rigid conformation, that can be further
suitably decorated to obtain new molecules with biological
activity. Therefore, it is very important to study and to
develop new scaleable synthetic routes able to construct fused
polyheterocyclic ring systems in high yields with a reduced
number of synthetic and purification steps. For this purpose,
microwave assisted organic synthesis (MAOS) continues to
affect synthetic chemistry by allowing us to obtain rapid,
reproducible, and scalable processes to synthesize new
molecules in high yield. Moreover, this methodology can
facilitate the discovery of new reactions, expanding the
possibilities of preparing new compounds or libraries for drug
discovery. The formation of heterocyclic rings by cyclization
reactions is typically a process well-suited for microwave
methodology. In fact, these reactions often require high
temperature for many hours or even days, whereas similar
or higher yields and cleaner reaction profiles can be obtained
by microwave heating for a few minutes.10–15 Our work
focused on the synthesis of the benzimidazoxazine nucleus
that were previously described only in 1985 by Mahesh.16
Here, a useful protocol for the preparation of this imidazole-
based privileged structures is described, starting from a
Results and Discussion
The preparation of the 4,5-disubstituted 2-(2-hydroxy-
phenyl)-1H-imidazoles (4-6) was here investigated (Scheme
1): the direct preparation from salicylaldehyde led to low
yields (between 30-67%) and required a chromatographic
purification of the products obtained, thus making this
synthetic route not suitable for scalable processes. The two-
step synthesis, through the methoxy derivatives, led to pure
compounds in higher yields (86-94%). Compounds 1-3
were thus prepared through solution-phase synthesis, starting
from phenylglyoxals or diketones and o-methoxybenzalde-
hyde, ammonium acetate as an ammonia source, and a polar
protic solvent, such as methanol at room temperature, to
afford the best yields of 4,5-disubstituted 2-(2-methoxy-
phenyl)-1H-imidazoles. The subsequent demethylation reac-
tion, that usually is lengthy and with poor yields, was carried
out employing microwave irradiation (HBr 48%, 150 °C for
10 min), able to produce the complete conversion in the
hydroxy derivative, with 86-95% isolated yields. These
intermediates were directly transformed, without further
purification, into the final products 7a-n, as shown in
Scheme 2. The nature of the imidazobenzoxazine obtained
depends on the cyclizing agent employed (CH2I2, for
compounds 7a-f, CDI, 1,1′-carbonyldiimidazole for com-
* Corresponding author. Tel.: +39-0521-905060. Fax: +39-0521-905006.
E-mail: mirko.rivara@unipr.it.
10.1021/cc900152y  2010 American Chemical Society
Published on Web 11/18/2009

182 Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 1
Fantini et al.
Scheme 1. Synthesis of the 2-(2-Hydroxy-phenyl)-4,5-disubstituted Imidazoles 4-6a
a Reagents and conditions: (i) CH3COONH4, CH3OH, rt, 2 h; (ii) 48% HBr, MW, 150 °C, 200 W, 10 min.
Scheme 2. Synthesis of the Imidazobenzoxazines,
Imidazobenzoxazin-5-ones, and Imidazobenzoxazin-5-thiones
7a-na
compared to conventional heating. Compounds 7a-f were
synthesized varying molar ratios of Cs2CO3 and solvent
(CH3CN instead of DMF) with respect to the above solution
phase synthesis. These new conditions led to very high yields
(75-98%), also reducing the time of reaction from 16 h to
10 min. Compounds 7g-j were prepared reducing the
amount of cyclizing agent (CDI) utilized in the “classical”
synthetic route, thus obtaining a significant increase of the
yields (80-98%) and a dramatic decrease of the reaction
time (20 min) (Table 1). Moreover, the various attempts
made to optimize the cyclization reactions highlighted that
MAOS did not have appreciable effects on the formation of
the isomers. In fact, all the tests carried out did not affect
the regioisomers ratio obtained with the traditional solution-
phase synthesis, while having very favorable effects on yields
and reaction times.
The optimized conditions found for the carbonyl com-
pounds were then applied to the synthesis of the imida-
zobenzoxazin-5-thiones 7k-n, also demonstrating the ver-
satility of the technique employed. As was observed before
for compounds 7g and 7h, only one isomer was formed in
the presence of a phenyl ring on the imidazole (7k and 7l).
a Reagents and conditions: solution phase synthesis (i) 7a-f ) CH2I2,
Cs2CO3, N,N-DMF, 100 °C, 16 h, (ii) 7g-j ) CDI, THF, rt, 24 h;
microwave heating (i) 7a-f ) CH2I2, Cs2CO3, CH3CN, MW, 80 °C, 150
W, 10 min, (ii) 7g-j ) CDI, THF, MW, 90 °C, 240 W, 20 min, (iii) 7k-n
) TCDI, THF, MW, 90 °C, 240 W, 10 min + 10 min with further addition
of the cyclizing agent.
Conclusion
pounds 7g-j, and TCDI, 1,1′-thiocarbonyldiimidazole for
compounds 7k-n). The products were prepared first under
conventional condition, and then, in order to reduce reaction
times and to improve the yields, microwave heating was
employed. The reaction conditions for the solution phase
synthesis of the imidazobenzoxazines 7a-f were investigated
using different reagents: paraformaldehyde, following the
procedure proposed by Burke,20 did not afford the desired
products, while CH2Br2 in DMF21,16 led to low yields. The
best conditions found (CH2I2, Cs2CO3, DMF, 16 h at 100
°C) determined the formation of two regioisomers, separated
and isolated in yields between 50 and 70%. The imidazoben-
zoxazin-5-ones 7g-j were prepared at first employing known
procedures indicated in the literature for the synthesis of
benzoxazinones,22,23 subsequently optimized due to the
different reactivity of the imidazole ring, to obtain higher
and acceptable yields (between 50 and 70% using CDI in
THF at rt). Interestingly, no regioselectivity was achieved
when CH2I2 was used as a cyclizing agent (compounds
7a-f), while with CDI only one isomer was recovered when
a phenyl ring is connected to the imidazole (7g and 7h).
These findings could be correlated with the steric hindrance
of the 1,1′-carbonyldiimidazole.
The described synthetic protocol allows for the preparation
of a series of imidazobenzoxazines, imidazobenzoxazin-5-
ones, and imidazobenzoxazin-5-thiones as new privileged
structures potentially useful for drug discovery. A microwave-
assisted synthesis was developed to provide small libraries
of privileged heterocyclic structures in high yields and with
clean and scalable reactions.
Experimental Section
Melting points are not corrected and were determined
using a Gallenkamp melting point apparatus. Solution phase
synthesis was made in parallel using a Bu¨chi Syncore
Reactor, while microwave assisted synthesis was performed
using a CEM Microwave SynthesizersDiscover Model. The
final products were analyzed on a ThermoQuest (Italia)
FlashEA 1112 Elemental Analyzer, for C, H, N. The
percentages recorded were within (0.4% of the theoretical
1
values. All products were also characterized by H NMR.
The 1H NMR spectra were recorded on a Bruker 300 Avance
spectrometer (300 MHz); chemical shifts (δ scale) are
reported in parts per million (ppm) relative to the central
1
peak of the solvent. H NMR spectra are reported in order:
In the next phase of this study, the same molecules were
prepared under microwave heating conditions, to investigate
the advantages of this technique. In fact, it is well docu-
mented that MAOS can lead to rate enhancement, higher
yields, less side reactions, and a better reproducibility
multiplicity and number of protons; signals were character-
ized as s (singlet), dd (doublet of doublet), t (triplet), m
(multiplet), br s (broad signal).
Solution Phase Synthesis. General Procedure for the
Synthesis of the 2-Methoxyphenyl-imidazoles 1-3. The

Synthesis of Imidazole-Based Privileged Structures
Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 1 183
Table 1. Synthesis of Imidazobenzoxazines, Imidazobenzoxazin-5-ones, and Imidazobenzoxazin-5-thiones 7a-n
a Conventional heating. b Isolated yield. c MAOS. d Not synthesized using conventional heating. e After 10 min another amount of TCDI was added.
opportune glyoxal or diketone (1.00 mmol) in 5.00 mL
methanol was added dropwise to a solution of 2-methoxy-
benzaldehyde (1.20 mmol) and ammonium acetate (4.87
mmol) in 5.00 mL methanol, and the mixture was stirred at
room temperature for 2 h. The solvent was evaporated and
the residue was partitioned between aqueous NaHCO3
solution and ethyl acetate. The organic phase was dried over
Na2SO4, and the solvent was removed in vacuo. The crude
products were then crystallized from methylene chloride/n-
hexane.
or diketone (1.00 mmol) in 5.00 mL methanol was added
dropwise to a solution of 2-hydroxybenzaldehyde (1.20
mmol) and ammonium acetate (4.87 mmol) in 5.00 mL
methanol, and the mixture was stirred at room temperature
for 2 h. The solvent was evaporated and the residue was
partitioned between aqueous HCl solution and methylene
chloride. Then, the aqueous phase was neutralized with
K2CO3, and the products were extracted with methylene
chloride. The organic phase was dried over Na2SO4, and the
solvent was removed in vacuo. The crude products were
purified by flash chromatography on silica gel using meth-
ylene chloride.
2-(2-Methoxyphenyl)-5-phenyl-1H-imidazole (1). Yield
1
86%. mp 116-118 °C. H NMR (300 MHz, DMSO-d6): δ
11.90 (br s, 1H), 8.20 (dd, 1H), 7.89 (dd, 2H), 7.64 (d, 1H),
7.38 (m, 3H), 7.18 (m, 2H), 7.05 (m, 1H), 3.94 (s, 3H).
2-(2-Methoxyphenyl)-4-methyl-5-phenyl-1H-imida-
zole (2). Yield 92%. mp 126-128 °C. 1H NMR (300 MHz,
DMSO-d6): δ 8.10 (dd, 1H), 7.72 (d, 2H), 7.35 (m, 3H),
7.21 (t, 1H), 7.13 (d, 1H), 7.03 (t, 1H), 3.95 (s, 3H), 2.50 (s,
3H).
2-(2-Methoxyphenyl)-4-methyl-5-propyl-1H-imida-
zole (3). Yield 94%. mp 106-108 °C. 1H NMR (300 MHz,
DMSO-d6): δ 7.99 (dd, 1H), 7.25 (m, 1H), 7.08 (d, 1H),
6.97 (t, 1H), 3.92 (s, 3H), 2.50 (s, 3H), 2.12 (br s, 2H), 1.55
(m, 2H), 0.89 (s, 3H).
2-(5-Phenyl-1H-imidazol-2-yl)phenol (4). Yield 30%. mp
176-178 °C. H NMR (300 MHz, DMSO-d6): δ 13.00 (s,
1H), 12.94 (s, 1H), 7.84 (m, 4H), 7.42 (t, 2H), 7.26 (t, 2H),
6.95 (m, 2H).
1
2-(4-Methyl-5-phenyl-1H-imidazol-2-yl)phenol (5). Yield
1
60%. mp 217-219 °C. H NMR (300 MHz, DMSO-d6): δ
13.01 (s, 1H), 12.77 (s, 1H), 7.83 (d, 1H), 7.64 (m, 2H),
7.47 (t, 2H), 7.26 (m, 2H), 6.93 (m, 2H), 2.50 (s, 3H).
2-(4-Methyl-5-propyl-1H-imidazol-2-yl)phenol (6). Yield
1
67%. mp 132-134 °C. H NMR (300 MHz, DMSO-d6): δ
13.21 (s, 1H), 12.35 (s, 1H), 7.74 (d, 1H), 7.16 (m, 1H),
6.86 (m, 2H), 2.50 (s, 3H), 2.18 (br s, 2H), 1.58 (m, 2H),
0.90 (t, 3H).
General Procedure for the Direct Synthesis of the
2-Hydroxyphenyl-imidazoles 4-6. The opportune glyoxal

184 Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 1
Fantini et al.
General Procedure for the Synthesis of the Imida-
zobenzoxazines 7a-f. A solution of the opportune hydrox-
yphenyl-imidazole (1.00 mmol), CH2I2 (4.00 mmol), and
Cs2CO3 (7.20 mmol) in 2 mL dry N,N-DMF was heated at
100 °C for 16 h. The reaction mixture was then treated with
methylene chloride and washed many times with water. The
organic phase was dried over Na2SO4 and the solvent was
removed in vacuo. The regioisomers so obtained were
separated on silica gel using methylene chloride/n-exane )
1/1.
3-Methyl-2-phenyl-5H-imidazo[1,2-c][1,3]benzoxazin-
5-one (7h). mp 140-143 °C. 1H NMR (300 MHz, DMSO-
d6): δ 8.00 (br s, 1H), 7.62 (br s, 2H), 7.49 (m, 1H), 7.33
(m, 5H), 2.64 (s, 3H). Anal. (C17H12N2O2) C, H, N: Ccalc
73.90%, Cfound 73.64%, Hcalc 4.38%, Hfound 4.48%, Ncalc
10.14%, Nfound 9.93%.
3-Methyl-2-propyl-5H-imidazo[1,2-c][1,3]benzoxazin-
5-one (7i). mp 81-83 °C. 1H NMR (300 MHz, DMSO-d6):
δ 7.90 (dd, 1H), 7.44 (m, 1H), 7.30 (m, 2H), 3.21 (s, 3H),
2.41 (t, 2H), 1.52 (m, 2H), 0.80 (t, 3H). Anal. (C14H16N2O2)
C, H, N: Ccalc 69.41%, Cfound 69.68%, Hcalc 5.82%, Hfound
5.95%, Ncalc 11.56%, Nfound 11.26%.
2-Phenyl-5H-imidazo[1,2-c][1,3]benzoxazine (7a). mp
1
134-138 °C. H NMR (300 MHz, DMSO-d6): δ 7.75 (m,
3H), 7.64 (s, 1H), 7.27 (m, 3H), 7.10 (m, 3H), 5.89 (s, 2H).
Anal. (C16H12N2O) C, H, N: Ccalc 77.40%, Cfound 77.00%,
Hcalc 4.87%, Hfound 4.84%, Ncalc 11.28%, Nfound 10.97%.
3-Phenyl-5H-imidazo[1,2-c][1,3]benzoxazine (7b). mp
2-Methyl-3-propyl-5H-imidazo[1,2-c][1,3]benzoxazin-
5-one (7j). mp 78-80 °C. 1H NMR (300 MHz, DMSO-d6):
δ 7.90 (dd, 1H), 7.46 (m, 1H), 7.32 (m, 2H), 2.79 (t, 2H),
2.11 (s, 3H), 1.48 (m, 2H), 0.78 (t, 3H). Anal. (C14H16N2O2)
C, H, N: Ccalc 69.41%, Cfound 69.78%, Hcalc 5.82%, Hfound
5.97%, Ncalc 11.56%, Nfound 11.35%.
1
144-148 °C. H NMR (300 MHz, DMSO-d6): δ 7.72 (dd,
1H), 7.37 (m, 4H), 7.28 (m, 2H), 7.21 (s, 1H), 7.08 (m, 2H),
5.96 (s, 2H). Anal. (C16H12N2O) C, H, N: Ccalc 77.40%, Cfound
77.04%, Hcalc 4.87%, Hfound 4.86%, Ncalc 11.28%, Nfound
11.07%.
Microwave Assisted Synthesis. General Procedure
for the Synthesis of the 2-Hydroxyphenyl-imidazoles
4-6 from the Methoxy Derivatives 1-3. A solution of the
opportune methoxyphenyl-imidazole (0.4 mmol) in 2 mL
48% HBr was prepared in a sealed 10 mL vial. The mixture
was irradiated for 10 min, setting the temperature at 150 °C
and the maximal power output at 200 W. During this period,
the reaction vessel was stirred and cooled (2 atm air). The
reaction mixture was neutralized with an aqueous saturated
NaHCO3 solution. The products were then extracted with
ethyl acetate, and the solvent was concentrated under reduced
pressure. The products so obtained were used in the
successive reaction without further purification. Yields: 95%
(compound 4), 95% (compound 5) and 86% (compound 6).
General Procedure for the Synthesis of the Imida-
zobenzoxazines 7a-f. A solution of the opportune hydrox-
yphenyl-imidazole (1.00 mmol), CH2I2 (4.00 mmol), and
Cs2CO3 (10.00 mmol) in 2 mL CH3CN was prepared in a
sealed 10 mL vial. The mixture was irradiated for 10 min,
setting the temperature at 80 °C and the maximal power
output at 150 W. During this period, the reaction vessel was
stirred and cooled (2 atm air). Then, Cs2CO3 was filtered
off and the solvent was concentrated under reduced pressure.
The regioisomers so obtained were separated on silica gel
using methylene chloride/n-exane ) 1:1.
General Procedure for the Synthesis of the Imida-
zobenzoxazin-5-ones 7g-j. A solution of the opportune
hydroxyphenyl-imidazole (0.80 mmol) and 1,1′-carbonyldi-
imidazole (CDI; 2.00 mmol) in 2 mL THF was prepared in
a sealed 10 mL vial. The mixture was irradiated for 20 min,
setting the temperature at 90 °C and the maximal power
output at 240 W. During this period, the reaction vessel was
stirred and cooled (2 atm air). The solvent was then
concentrated under reduced pressure and the imidazoben-
zoxazinones were purified on silica gel using methylene
chloride/n-hexane ) 1/1.
3-Methyl-2-phenyl-5H-imidazo[1,2-c][1,3]benzoxazine (7c).
1
mp 129-132 °C. H NMR (300 MHz, DMSO-d6): δ 7.70
(dd, 1H), 7.58 (br s, 2H), 7.31 (t, 2H), 7.23 (m, 1H), 7.14
(m, 1H), 7.05 (m, 2H), 5.86 (s, 2H), 2.33 (s, 3H). Anal.
(C17H14N2O · 0.2H2O) C, H, N: Ccalc 76.78%, Cfound 76.79%,
Hcalc 5.45%, Hfound 5.31%, Ncalc 10.53%, Nfound 10.36%.
2-Methyl-3-phenyl-5H-imidazo[1,2-c][1,3]benzoxazine (7d).
1
mp 116-120 °C. H NMR (300 MHz, DMSO-d6): δ 7.69
(dd, 1H), 7.40 (br s, 2H), 7.26 (m, 4H), 7.05 (m, 2H), 5.76
(s, 2H), 2.13 (s, 3H). Anal. (C17H14N2O) C, H, N: Ccalc
77.84%, Cfound 77.95%, Hcalc 5.38%, Hfound 5.41%, Ncalc
10.68%, Nfound 10.65%.
3-Methyl-2-propyl-5H-imidazo[1,2-c][1,3]benzoxazine
(7e). mp 90-93 °C. 1H NMR (300 MHz, DMSO-d6): δ 7.57
(dd, 1H), 7.15 (m, 1H), 6.99 (m, 2H), 5.73 (s, 2H), 2.31 (t,
2H), 2.06 (s, 3H), 1.46 (m, 2H), 0.77 (t, 3H). Anal.
(C14H16N2O) C, H, N: Ccalc 73.66%, Cfound 73.33%, Hcalc
7.06%, Hfound 7.12%, Ncalc 12.27%, Nfound 11.88%.
2-Methyl-3-propyl-5H-imidazo[1,2-c][1,3]benzoxazine
1
(7f). oil. H NMR (300 MHz, DMSO-d6): δ 7.57 (dd, 1H),
7.16 (m, 1H), 7.00 (m, 2H), 5.73 (s, 2H), 2.43 (t, 2H), 2.00
(s, 3H), 1.34 (m, 2H), 0.76 (t, 3H). Anal. (C14H16N2O) C,
H, N: Ccalc 73.66%, Cfound 73.73%, Hcalc 7.06%, Hfound 7.32%,
Ncalc 12.27%, Nfound 11.96%.
General Procedure for the Synthesis of the Imida-
zobenzoxazin-5-ones 7g-j. A solution of the opportune
hydroxyphenyl-imidazole (1.00 mmol) and 1,1′-carbonyldi-
imidazole (CDI; 3.00 mmol) in 2 mL THF was stirred at
room temperature for 24 h. The solvent was then concen-
trated under reduced pressure and the imidazobenzoxazinones
were purified on silica gel using methylene chloride/n-hexane
) 1/1.
2-Phenyl-5H-imidazo[1,2-c][1,3]benzoxazin-5-one (7g).
1
mp 200-204 °C. H NMR (300 MHz, DMSO-d6): δ 8.36
General Procedure for the Synthesis of the Imida-
zobenzoxazin-5-thiones 7k-n. A solution of the opportune
hydroxyphenyl-imidazole (0.80 mmol) and 1,1′-thiocarbo-
nyldiimidazole (TCDI; 2.00 mmol) in 2 mL THF was
prepared in a sealed 10 mL vial and was irradiated for 10
(s, 1H), 8.07 (dd, 1H), 7.94 (dd, 2H), 7.55 (m, 1H), 7.40
(m, 4H), 7.25 (m, 1H). Anal. (C16H10N2O2 · 0.2H2O) C, H,
N: Ccalc 72.28%, Cfound 72.35%, Hcalc 3.94%, Hfound 3.93%,
Ncalc 10.53%, Nfound 10.36%.

Synthesis of Imidazole-Based Privileged Structures
Journal of Combinatorial Chemistry, 2010 Vol. 12, No. 1 185
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min, setting the temperature at 90 °C and the maximal power
output at 240 W. The mixture so obtained was further added
of TCDI (1.00 mmol) and heated at 90 °C for other 10 min,
with the maximal power output at 240 W. During this period,
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using methylene chloride/n-hexane ) 1/1.
2-Phenyl-5H-imidazo[1,2-c][1,3]benzoxazin-5-thione (7k).
1
mp 206-208 °C. H NMR (300 MHz, DMSO-d6): δ 8.60
(s, 1H), 8.23 (d, 1H), 8.10 (d, 2H), 7.73 (m, 2H), 7.58 (m,
1H), 7.48 (t, 2H), 7.39 (t, 1H). Anal. (C16H10N2OS) C, H,
N: Ccalc 69.04%, Cfound 68.77%, Hcalc 3.62%, Hfound 3.55%,
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3-Methyl-2-phenyl-5H-imidazo[1,2-c][1,3]benzoxazin-
5-thione (7l). mp 158-160 °C. 1H NMR (300 MHz, DMSO-
d6): δ 8.14 (d, 1H), 7.70 (m, 2H), 7.51 (m, 6H), 2.91 (s,
3H). Anal. (C17H12N2OS) C, H, N: Ccalc 69.84%, Cfound
69.45%, Hcalc 4.14%, Hfound 4.14%, Ncalc 9.58%, Nfound 9.37%.
3-Methyl-2-propyl-5H-imidazo[1,2-c][1,3]benzoxazin-
5-thione (7m). mp 117-119 °C. 1H NMR (300 MHz,
DMSO-d6): δ 8.06 (d, 1H), 7.58 (m, 2H), 7.46 (t, 1H), 2.71
(s, 3H), 2.56 (t, 2H), 1.64 (m, 2H), 0.92 (t, 3H). Anal.
(C14H16N2OS) C, H, N: Ccalc 65.09%, Cfound 65.49%, Hcalc
5.46%, Hfound 5.79%, Ncalc 10.84%, Nfound 10.46%.
2-Methyl-3-propyl-5H-imidazo[1,2-c][1,3]benzoxazin-
5-thione (7n). mp 98-100 °C. 1H NMR (300 MHz, DMSO-
d6): δ 8.09 (dd, 1H), 7.61 (m, 2H), 7.48 (t, 1H), 3.21 (t,
2H), 2.27 (s, 3H), 1.62 (m, 2H), 0.91 (t, 3H). Anal.
(C14H16N2OS) C, H, N: Ccalc 65.09%, Cfound 65.29%, Hcalc
5.46%, Hfound 5.45%, Ncalc 10.84%, Nfound 10.58%.
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Acknowledgment. Financial support from Italian MIUR
is gratefully acknowledged. We are grateful to the Centro
Interdipartimentale Misure of the University of Parma for
providing the NMR instrumentation.
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References and Notes
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