Diversity oriented synthesis of fused-ring 1,3-oxazines from carbohydrates as biorenewable feedstocks

Article abstract of DOI:10.1016/j.tet.2008.02.084

Microwave enhanced diversity oriented synthesis (MEDOS) of various N- and O-heterocyclic systems fused with 1,3-oxazine ring is reported. The synthesis represents a new montmorillonite K-10 clay-catalyzed green protocol, which utilizes d-glucose/d-xylose as biorenewable feedstocks. d-Glucose/d-xylose-derived 1,3-oxazin-2-ones(thiones) either directly undergo K-10 clay-catalyzed cyclization to yield pyrano-/furo-1,3-oxazine systems under solvent-free microwave irradiation conditions or afford azolo-/azino-1,3-oxazines when subjected to Malaprade reaction followed by cyclization with appropriate reagents, viz. phenylhydrazine, hydroxylamine, acetamidine, phenylurea and semi(thiosemi)carbazide.

Full text of DOI:10.1016/j.tet.2008.02.084

Available online at www.sciencedirect.com
Tetrahedron 64 (2008) 4246e4253
www.elsevier.com/locate/tet
Diversity oriented synthesis of fused-ring 1,3-oxazines from
carbohydrates as biorenewable feedstocks
*
Lal Dhar S. Yadav , Vishnu P. Srivastava, Vijai K. Rai, Rajesh Patel
Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211 002, India
Received 16 December 2007; received in revised form 22 February 2008; accepted 26 February 2008
Available online 29 February 2008
Abstract
Microwave enhanced diversity oriented synthesis (MEDOS) of various N- and O-heterocyclic systems fused with 1,3-oxazine ring is
reported. The synthesis represents a new montmorillonite K-10 clay-catalyzed green protocol, which utilizes D-glucose/D-xylose as biorenewable
feedstocks. D-Glucose/D-xylose-derived 1,3-oxazin-2-ones(thiones) either directly undergo K-10 clay-catalyzed cyclization to yield pyrano-/
furo-1,3-oxazine systems under solvent-free microwave irradiation conditions or afford azolo-/azino-1,3-oxazines when subjected to Malaprade
reaction followed by cyclization with appropriate reagents, viz. phenylhydrazine, hydroxylamine, acetamidine, phenylurea and semi(thiosemi)-
carbazide.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Diversity oriented synthesis; 1,3-Oxazines; Solvent-free; Microwaves; Montmorillonite K-10; Carbohydrates
1. Introduction
(Efavirenz), a non-nucleoside reverse transcriptase inhibitor
that has been approved by the FDA in 1998 and is presently
in clinical use for the treatment of AIDS.10b This has been
the prime driving force for the synthesis of various compounds
incorporating the 1,3-oxazine moiety. 1,3-Oxazin-2-one deriva-
tives have been used as the key intermediates in the synthesis
of several natural products, and have also been recognized as
chiral auxiliaries in asymmetric synthesis.11
Along with the synthetic strategies reported in the literature
for oxazines,12e19 we have also reported the synthesis of 1,3-
oxazin-2-ones(thiones) fused with benzene ring20e23 and their
C- and N-nucleoside analogues using salicylaldehyde as a
bifunctional building block.24e26 To the best of our knowledge,
there has been no report on the synthesis of 1,3-oxazin-2-one-
(thione) fused with various pharmaceutically and agrochemi-
cally important N- and O-heterocycles, starting from D-glucose
and D-xylose, although they appear to be attractive scaffolds to
be utilized for exploiting chemical diversity and generating
a drug-like library to screen for potential new leads.
Diversity oriented synthesis (DOS) has emerged as a valu-
able approach to generate libraries of various classes of com-
pounds.1e5 Efforts in DOS have produced powerful new
biological probes and also served as a new driving force for
synthetic organic chemistry. Although the earlier combina-
torial chemical libraries of drug-like small molecules were
reported over a decade ago,6 DOS remains relatively less
extensively studied.
Carbohydrates are the major raw materials for organic
chemicals with tailor-made industrial applications. This is be-
cause they are inexpensive, accessible in ton-scale and have
better worked out ensuing chemistry. Advantages of the appli-
cation of microwave (MW) irradiation in conjunction with
mineral supported reagents under solvent-free conditions
have now been well established.
The 1,3-oxazine nucleus features prominently in many
biologically important natural products7 and other bioactive
molecules.8e10 The most outstanding of these is Sustiva
Considering the above valid points and our ongoing efforts
to develop new cyclization processes,20e28 we describe herein
the microwave enhanced diversity oriented synthetic (MEDOS)
approach for the unprecedented synthesis of pharmaceutically
* Corresponding author. Tel.: þ91 5322500652; fax: þ91 5322460533.
E-mail address: ldsyadav@hotmail.com (L.D.S. Yadav).
0040-4020/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.02.084

L.D.S. Yadav et al. / Tetrahedron 64 (2008) 4246e4253
4247
X
and agrochemically important furo-, isoxazolo-, oxazino-, pyr-
H2NNHCNH2
(X = O, S)
azolo-, pyrano-, pyrimidino-, pyrazinoxazin-2-ones(thiones)
and oxazinoxazin-2,6-ones(thiones) using D-glucose and D-xy-
lose under solvent-free mineral supported reaction conditions
(Scheme 1).
N
CHO
(CHOH)
CH2OH
n = 3, D-xylose
n = 4, D-glucose
HO
NH
NH2
n
2
OH
X
MW, K-10 clay
(CHOH)
n-2
CH2OH
4
X
1
H2NNHCNH2
(X = O, S)
2
HO
CHO
(CHOH)
CH2OH
HO
N.NH2
NH2
N
N
K-10
clay
MW
10 min
n
HO
NH
O(S)
O
NH2
(CHOH)
MW, K-10 clay
n-2
O
X
X
n = 3, D-xylose
n = 4, D-glucose
O
(CHOH)
n-2
CH2OH
H
(CHOH)
n-2
CH2OH
CH2OH
1
O
N
3
HO
NH.NH2
N
O(S)
O
O
N
O
HO
N
N
HO
OH
N
H
X
O
-NH2NH2
O(S)
O(S)
O
O
HO
(CHOH)
n-2
X
O
OH
(CHOH)
CH2OH
n-2
Ph
N
Ph
N
3a, X = O, n = 3
3b, X = S, n = 3
3c, X = O, n = 4
3d, X = S, n = 4
CH2OH
N
N
N
N
1,3-oxazin-2-one(thione)
3
O(S)
O
O(S)
O
OH
O
Scheme 2. Plausible mechanism for the formation of 1,3-oxazin-2-ones-
(thiones) 3 from D-glucose/D-xylose semi(thiosemi)carbazones 4.
N
N
O
O
N
O(S)
Me
O
N
O(S)
O
O
O
N
N
N
by recrystallization from ethanol afforded 7e9 in 80e93%
yields. Similarly, compounds 10 and 11 were synthesized in
81e92% yields by MW irradiation of an intimate solvent-
free mixture of compound 6, montmorillonite K-10 clay and
sodium acetate with hydroxylamine hydrochloride and phenyl-
hydrazine hydrochloride, respectively, at 90 ꢀC for 5e11 min
(Scheme 5).
N
N
Ph
O(S)
O
O(S)
O
NH2
Scheme 1. MEDOS of fused-ring 1,3-oxazin-2-ones(thiones) from D-glucose
and D-xylose.
2. Results and discussion
HO
N
The hitherto unreported 1,3-oxazin-2-ones(thiones) 3 were
obtained via montmorillonite K-10 clay-catalyzed domino
cycloisomerization, dehydrazination and dehydration of
D-glucose/D-xylose semi(thiosemi)carbazones 4 under solvent-
free MW irradiation conditions in a one-pot procedure
(Scheme 2). The mechanism shown in Scheme 2 is supported
by the formation of hydrazine during the reaction. It was noted
that other mineral catalysts, viz. silica gel, neutral or basic
alumina, were far less effective resulting in either no reaction
(in the case of basic alumina) or relatively very low yields
(15e28%) of 3 (in the cases of silica gel and neutral alumina).
1,3-Oxazin-2-ones(thiones) 3 were synthesized in 79e85%
yields by solvent-free MW irradiation of D-glucose/D-xylose 1,
semi(thiosemi)carbazide 2 and montmorillonite K-10 clay
(Scheme 2). 1,3-Oxazin-2-ones(thiones) 3 were subjected to
Malaprade reaction (Scheme 3) to afford aldehydes 5 and 6,
which were converted into the target compounds 7e11; com-
pounds 14 and 16 by judicious use of catalysts and reagents
(Schemes 4, 5, 7 and 8). The MEDOS strategy for the envis-
aged solvent-free synthesis of 1,3-oxazin-2-one(thione)-fused
isoxazoles 7, pyrazoles 8 and pyrimidines 9 consisted in mi-
crowave (MW) irradiation of an intimate solvent-free mixture
of compound 5, montmorillonite K-10 clay and sodium acetate
with hydroxylamine hydrochloride, phenylhydrazine hydro-
chloride and acetamidine hydrochloride, respectively, at
80 ꢀC for 5e12 min (Scheme 4). Isolation and purification
H
X
O
aq. NaIO4
2 equiv
O
O
5a, X = O
5b, X = S
HO
OH
N
X
HO
O
HO
N
aq. NaIO4
1 equiv
OH
X
O
H
3c, X = O
3d, X = S
OH
6a, X = O
6b, X = S
Scheme 3. Malaprade reaction to afford aldehydes 5 and 6.
The formation of compounds 7e11 may be tentatively ex-
plained by acid-catalyzed condensation of hydroxylamine,
phenylhydrazine or acetamidine with aldehydic pC]O group
of 5 and 6 followed by cyclodehydration of the resulting con-
densation product (Schemes 4 and 5). Montmorillonite K-10
clay-catalyzed cyclodehydration of 1,3-oxazin-2-ones(thiones)
3 (Scheme 6) under solvent-free MW irradiation afforded furo-
1,3-oxazin-2-ones(thiones) 12 (83e85% yields) and pyrano-
1,3-oxazin-2-ones(thiones) 13 in 87e90% yields (Table 1).
The use of other mineral catalysts, viz. silica gel, neutral or
basic alumina, resulted in relatively very low yields of 7e9
(19e35%) and 21e29% of 12 and 13.
The MEDOS strategy for compounds 14 was successful
when an intimate mixture of phenylurea, ammonium acetate,

4248
L.D.S. Yadav et al. / Tetrahedron 64 (2008) 4246e4253
HO
H
O
N
OH
Ph
N
H
OH
PhNHNH2
NH2OH
H
N
N
-H2O
N
X
O
AcONa
K-10
MW
AcONa
K-10
MW
N
X
O
O
X
5a, X = O
5b, X = S
O
O
N
O
7a, X = O
7b, X = S
N
X
AcONa
K-10
MeC=NH
NH2
-H2O
MW
H
N
Ph
N
OH
Me
N
Me
N
N
O
8a, X = O
8b, X = S
N
N
-H2O
N
N
X
O
X
X
O
9a, X = O
9b, X = S
Scheme 4. Routes for the formation of compounds 7e9 from compounds 5.
O
H
Table 1
Microwave enhanced synthesis of compounds 3, 4 and 7e16 under solvent-
free conditions
N
N
N
OH
O
NH2OH
6
N
N
X
AcONa
K-10
MW
O
-H2O
-H2O
OH
X
X
Timea
(min)
Yieldb,c
(%)
Compound
Timea
(min)
Yieldb,c
(%)
O
Compound
10a, X = O
10b, X = S
OH
H
Ph
N
3a
3b
3c
3d
7a
7b
8a
8b
9a
9b
10a
a
3
2
83
79
81
85
80
83
91
93
85
82
81
10b
11a
11b
12a
12b
13a
13b
14a
14b
16a
16b
7
9
88
92
91
85
83
90
87
89
93
91
90
Ph
N
OH
N
N
PhNHNH2
6
N
2
11
8
AcONa
K-10
MW
X
O
4
O
OH
11a, X = O
11b, X = S
5
8
OH
5
7
12
11
7
8
Scheme 5. Formation of compounds 10 and 11 from 6.
10
9
H
9
11
8
5
O
MW
K-10
-H2O
O
HO
N
N
Microwave irradiation time.
Yield of isolated and purified products.
All compounds gave C, H and N analyses within ꢁ0.36%, and satisfactory
b
c
X
X
O
O
HO
HO
OH
12a, X = O
12b, X = S
3a, X = O
3b, X = S
spectral (IR, 1H NMR, 13C NMR and EIMS) data.
H
H
O
O
MW
K-10
HO
O
N
N
N
N
O
O
O
C
X
X
-H2O
X
O
N
O
O
5
MW
K-10
-NH3
HO
X
O
PhHN
NH2
Ph
Phenyl
isocyanate
OH
OH
Phenylurea
13a, X = O
13b, X = S
3c, X = O
3d, X = S
O
O
O
O
O
NH4OAc
Scheme 6. Formation of compounds 12 and 13 from 3.
N
X
PhHN:
PhHN
O
NH
14'
K-10 clay and 5 was subjected to MW irradiation for
9e10 min at 90 ꢀC (Scheme 7). Isolation and purification by
recrystallization from ethanol afforded 4-amino oxazine-2,6-
diones(6-one-2-thiones) 14 in 89e93% yields (Table 1).
That the first step in the present three component coupling
strategy involves the conversion of phenylurea into phenyl iso-
cyanate intermediate was supported by its trapping as p-tolyl-
urea derivatives. Phenylurea with ammonium acetate and 5
yielded an aldimine intermediate 140, which upon cycloiso-
merization afforded compounds 14 (Scheme 7). Furthermore,
MW irradiation of thoroughly mixed semicarbazones 15 and
Montmorillonite K-10 clay at 90 ꢀC for 8e11 min afforded
compounds 16 in 90e91% yields (Table 1) via domino cyclo-
isomerization and dehydrazination reactions of 15 (Scheme 8).
O
O
N
N
X
Ph
O
NH2
14a, X = O
14b, X = S
Scheme 7. Plausible mechanism for the formation of compounds 14 from
phenylurea.
The mechanism shown in Scheme 8 is supported by the forma-
tion of hydrazine during the reaction. The relatively poor
yields (11e19%) of 16 were obtained by using other mineral
catalysts, viz. silica gel, neutral or basic alumina.

L.D.S. Yadav et al. / Tetrahedron 64 (2008) 4246e4253
4249
H
O
O
H2N
HN
H
O
HO
H
O
H2N
HN
N
NH CONHNH HCl
K-10
·
2
2
N
N
AcONa
MW, K-10
O
N
X
O
X
X
N
O
O
X
5a, X = O
5b, X = S
15
O
O
O
O
O
O
N
N
N
N
N
-NHNH2
H2N:
O
O
H
X
O
X
NHNH2
NNH2
16a, X = O
16b, X = S
15'
Scheme 8. Plausible mechanism for the formation of 15 from 16.
3. Conclusion
3.85 (dd, 1H, J4H,5H¼8.1 Hz, J5H,6H¼3.4 Hz, 5-H), 4.11
0 0 0 0
(dd, 1H, J2 Ha,2 Hb¼10.1 Hz, J1 H,2 Ha¼5.4 Hz, 20Ha), 4.23
0
In summary, we have developed a general, straightforward
diversity oriented synthetic approach for the synthesis of
various 1,3-oxazin-2-one(thione)-fused N- and O-heterocyclic
systems using D-glucose and D-xylose as biorenewable re-
sources under solvent-free microwave irradiation conditions.
The present protocol is an excellent illustration for the utiliza-
tion of carbohydrate feedstocks in organic synthesis.
(dd, 1H, J6H,1 H¼6.1 Hz, J5H,6H¼3.4 Hz, 6-H), 4.30 (ddd,
1H, J6H,1 H¼6.1 Hz, J1 H,2 Ha¼5.4 Hz, J1 H,2 Hb¼2.9 Hz, 10H),
0
0
0
0
0
4.63 (dd, 1H, J2 Ha,2 Hb¼10.1 Hz, J1 H,2 Hb¼2.9 Hz, 20Hb),
4.93e5.24 (br s, 3H, 3ꢃOH, exchangeable with D2O), 7.65
(d, 1H, J4H,5H¼8.1 Hz, 4-H). 13C NMR (DMSO-d6/TMS) d:
64.5, 65.3, 73.7, 86.2, 163.1, 172.5. MS (FAB) m/z 176
(MHþ). Anal. Calcd for C6H9NO5: C, 41.15; H, 5.18; N,
8.00%. Found: C, 41.43; H, 5.09; N, 7.82%.
0
0
0
0
4. Experimental
4.2.2. Compound 3b
White solid (79%), mp 156e158 ꢀC. IR (KBr) nmax 3391e
.
3385, 3015, 1695, 1636 cmꢂ1 1H NMR (DMSO-d6/TMS)
4.1. General
Melting points were determined by open glass capillary
method and are uncorrected. IR spectra in KBr were recorded
on a PerkineElmer 993 IR spectrophotometer. 1H NMR
spectra were recorded on a Bruker WM-40 C (400 MHz) FT
spectrometer in DMSO-d6 using TMS as an internal reference.
13C NMR spectra were recorded on the same instrument at
100 MHz in DMSO-d6 and TMS was used as internal reference.
Mass (EI) spectra were recorded on a JEOL D-300 mass spec-
trometer. Elemental analyses were carried out in a Coleman
automatic carbon, hydrogen and nitrogen analyzer. A Chemical
Laboratory Microwave Oven (Model: BP-310/50, 230 volt,
50 Hz power input) was used for all the experiments. All chem-
icals used were of reagent grade and were used as-received
without further purification. Silica gel-G was used for TLC.
d: 3.87 (dd, 1H, J4H,5H¼8.1 Hz, J5H,6H¼3.4 Hz, 5-H), 4.10
(dd, 1H, J2 Ha,2 Hb¼10.2 Hz, J1 H,2 Ha¼5.4 Hz, 20Ha), 4.19
0
0
0
0
0
(dd, 1H, J6H,1 H¼6.1 Hz, J5H,6H¼3.4 Hz, 5-H), 4.33 (ddd,
1H, J6H,1 H¼6.1 Hz, J1 H,2 Ha¼5.4 Hz, J1 H,2 Hb¼2.9 Hz, 10H),
0
0
0
0
0
4.59 (dd, 1H, J2 Ha,2 Hb¼10.2 Hz, J1 H,2 Hb¼2.9 Hz, 20Hb),
4.93e5.27 (br s, 3H, 3ꢃOH, exchangeable with D2O), 7.69
(d, 1H, J4H,5H¼8.1 Hz, 4-H). 13C NMR (DMSO-d6/TMS) d:
64.4, 65.7, 71.9, 85.7, 104.8, 163.0, 192.3. MS (FAB) m/z
192 (MHþ). Anal. Calcd for C6H9NO4S: C, 37.69; H, 4.74;
N, 7.33%. Found: C, 37.95; H, 4.91; N, 7.23%.
0
0
0
0
4.2.3. Compound 3c
White solid (81%), mp 161e164 ꢀC. IR (KBr) nmax 3398e
1
3382, 3008, 1690, 1635 cmꢂ1. H NMR (DMSO-d6/TMS) d:
0
0
0
0
0
0
3.88 (ddd, 1H, J2 H,3 Ha¼5.4 Hz, J1 H,2 H¼4.6 Hz, J2 H,3 Hb
¼
4.2. 1,3-Oxazin-2-ones(thiones) 3: general procedure
2.7 Hz, 20H), 3.91 (dd, 1H, J4H,5H¼8.1 Hz, J5H,6H¼3.1 Hz,
0
0
0
0
5-H), 4.03 (dd, 1H, J3 Ha,3 Hb¼10.5 Hz, J2 H,3 Ha¼5.4 Hz,
0
ThoroughlymixedD-xylose/D-glucose(1 mmol)1, semicarb-
azide hydrochloride/thiosemicarbazide (1 mmol) 2, sodium
acetate (1 mmol) and montmorillonite K-10 clay (0.10 g)
were taken in a 20 mL vial and subjected to microwave irradi-
ation for 2e4 min at 90 ꢀC. After completion of the reaction as
indicated by TLC, water (10 mL) was added to give the crude
product and recrystallized from ethanol to obtain analytically
pure sample of 3.
30Ha), 4.27 (dd, 1H, J6H,1 H¼6.7 Hz, J5H,6H¼3.1 Hz, 6-H),
4.37 (dd, 1H, J6H,1 H¼6.7 Hz, J1 H,2 H¼4.6 Hz, 10H), 4.59
0
0
0
(dd, 1H, J3 Ha,3 Hb¼10.5 Hz, J2 H,3 Hb¼2.7 Hz, 30Hb), 5.01e
5.37 (br s, 4H, 4ꢃOH, exchangeable with D2O), 7.63 (d,
1H, J4H,5H¼8.1 Hz, 4-H). 13C NMR (DMSO-d6/TMS):
d 55.7, 64.3, 65.9, 71.7, 73.5, 81.5, 163.2, 174.8. MS (FAB)
m/z 206 (MHþ). Anal. Calcd for C7H11NO6: C, 40.98; H,
5.40; N, 6.83%. Found: C, 40.73; H, 5.57; N, 6.71%.
0
0
0
0
4.2.1. Compound 3a
White solid (83%), mp 147e149 ꢀC. IR (KBr) nmax 3392e
4.2.4. Compound 3d
White solid (85%), mp 142e144 ꢀC. IR (KBr) nmax 3399e
1
1
3385, 3011, 1692, 1635 cmꢂ1. H NMR (DMSO-d6/TMS) d:
3384, 3012, 1693, 1638 cmꢂ1. H NMR (DMSO-d6/TMS) d:

4250
L.D.S. Yadav et al. / Tetrahedron 64 (2008) 4246e4253
0
0
0
0
0
0
0
3.81 (ddd, 1H, J2 H,3 Ha¼5.4 Hz, J1 H,2 H¼4.6 Hz, J2 H,3 Hb
¼
J1 H,6H¼5.9 Hz, J5H,6H¼3.5 Hz, 6-H), 7.61 (d, 1H,
2.7 Hz, 20H), 3.90 (dd, 1H, J4H,5H¼8.1 Hz, J5H,6H¼3.1 Hz,
J4H,5H¼7.8 Hz, 4-H), 9.91 (s, 1H, CHO). 13C NMR (DMSO-
d6/TMS) d: 62.5, 78.1, 91.8, 163.7, 172.1, 176.8. MS (FAB)
m/z 174 (MHþ). Anal. Calcd for C6H7NO5: C, 41.63; H,
4.08; N, 8.09%. Found: C, 41.43; H, 4.29; N, 8.23%.
0
0
0
0
5-H), 4.04 (dd, 1H, J3 Ha,3 Hb¼10.5 Hz, J2 H,3 Ha¼5.4 Hz,
30Ha), 4.23 (dd, 1H, J6H,1 H¼6.7 Hz, J5H,6H¼3.1 Hz, 6-H),
0
4.41 (dd, 1H, J6H,1 H¼6.7 Hz, J1 H,2 H¼4.6 Hz, 10H), 4.57
0
0
0
(dd, 1H, J3 Ha,3 Hb¼10.5 Hz, J2 H,3 Hb¼2.7 Hz, 30Hb), 5.03e
5.33 (br s, 4H, 4ꢃOH, exchangeable with D2O), 7.66 (d,
1H, J4H,5H¼8.1 Hz, 4-H). 13C NMR (DMSO-d6/TMS):
d 55.6, 64.8, 65.6, 71.6, 73.8, 81.3, 163.1, 192.9. MS (FAB)
m/z 222 (MHþ). Anal. Calcd for C7H11NO5S: C, 38.00; H,
5.01; N, 6.33%. Found: C, 38.32; H, 5.16; N, 6.29%.
0
0
0
0
4.3.4. Compound 6b
White solid (78%), mp 105e107 ꢀC. IR (KBr) nmax 3395,
3385, 3015, 1716, 1637, 1058 cmꢂ1. H NMR (DMSO-d6/
1
TMS) d: 3.73 (d, 1H, J1 H,6H¼5.9 Hz, 10H), 4.05 (dd, 1H,
0
J4H,5H¼8.1 Hz, J5H,6H¼3.5 Hz, 5-H), 5.03e5.27 (br s, 2H,
0
2ꢃOH, exchangeable with D2O), 5.61 (dd, 1H, J1 H,6H
¼
4.3. Malaprade reaction to afford aldehydes 5 and 6: general
procedure
5.9 Hz, J5H,6H¼3.5 Hz, 6-H), 7.57 (d, 1H, J4H,5H¼8.1 Hz,
4-H), 9.90 (s, 1H, CHO). 13C NMR (DMSO-d6/TMS) d:
62.1, 78.3, 92.7, 162.9, 176.1, 192.2. MS (FAB) m/z 190
(MHþ). Anal. Calcd for C6H7NO4S: C, 38.09; H, 3.73; N,
7.40%. Found: C, 38.39; H, 3.49; N, 7.76%.
To a well stirred ice-cold solution of 1,3-oxazin-2-ones-
(thiones) 3 (1 mmol) in 15 mL ethanol was added dropwise
with stirring a solution of sodium periodate (2 mmol) in
8 mL of water. The reaction mixture was further stirred for
2e3 h at rt. After completion of reaction, as indicated by
TLC, solvent was evaporated under reduced pressure to get
solid residue, which was extracted with ethyl acetate
(3ꢃ10 mL). The extract was filtered and filtrate was concen-
trated under vacuum to leave the crude product, which on
recrystallization from ethanol afforded pure compounds 5 as
white solid. The procedure followed for 6 was exactly the
same, except that in this case 1 mmol of sodium periodate
was used instead of 2 mmol of sodium periodate for 5.
4.4. Isoxazolo-, pyrazolo- and pyrimidinoxazin-2-
ones(thiones) 7e9: general procedure
An intimate solvent-free mixture of 5 (0.143 g for 5a,
1 mmol), sodium acetate (0.082 g, 1 mmol) and hydroxyl-
amine hydrochloride (0.069 g, 1 mmol) or phenylhydrazine
hydrochloride (0.145 g, 1 mmol) or acetamidine hydrochloride
(0.095 g, 1 mmol) in the presence of montmorillonite K-10
clay (0.10 g) was taken in a 20 mL vial and subjected to
MW irradiation at 80 ꢀC for 5e12 min to get the crude prod-
uct, which was extracted with dichloromethane (3ꢃ10 mL).
The extract was filtered, the filtrate was evaporated under re-
duced pressure and the residue thus obtained was recrystal-
lized from ethanol to obtain as analytically pure sample of
compound 7, 8 or 9 as a yellowish solid.
4.3.1. Compound 5a
White solid (74%), mp 120e122 ꢀC. IR (KBr) nmax 3391,
3009, 1715, 1695, 1632 cmꢂ1. H NMR (DMSO-d6/TMS) d:
1
3.98 (dd, 1H, J4H,5H¼7.8 Hz, J5H,6H¼3.2 Hz, 5-H), 4.95 (br
s, 1H, OH, exchangeable with D2O), 5.57 (d, 1H, J5H,6H
¼
3.2 Hz, 6-H), 7.53 (d, 1H, J4H,5H¼7.8 Hz, 4-H), 9.85 (s, 1H,
CHO). 13C NMR (DMSO-d6/TMS) d: 61.9, 92.5, 163.1,
172.5, 176.5. MS (FAB) m/z 144 (MHþ). Anal. Calcd for
C5H5NO4: C, 41.97; H, 3.52; N, 9.79%. Found: C, 41.73; H,
3.47; N, 9.92%.
4.4.1. Compound 7a
Yellowish solid (80%), mp 164e166 ꢀC. IR (KBr) nmax 3010,
1691, 1639 cmꢂ1. 1H NMR (DMSO-d6/TMS) d: 3.91 (dd, 1H,
J4aH,4H¼8.7 Hz, J4aH,7aH¼3.5 Hz, 4a-H), 5.17 (dd, 1H, J7aH,7H
¼
9.1 Hz, J4aH,7aH¼3.5 Hz, 7a-H), 7.56 (d, 1H, J4aH,4H¼8.7 Hz,
4-H), 7.64 (d, 1H, J7aH,7H¼9.1 Hz, 7-H). 13C NMR (DMSO-
d6/TMS) d: 65.5, 72.3, 159.2, 161.5, 173.4. MS (FAB) m/z 141
(MHþ). Anal. Calcd for C5H4N2O3: C, 42.87; H, 2.88; N,
20.00%. Found: C, 43.18; H, 2.53; N, 19.89%.
4.3.2. Compound 5b
White solid (79%), mp 132e134 ꢀC. IR (KBr) nmax 3390,
3011, 1718, 1635, 1055 cmꢂ1. H NMR (DMSO-d6/TMS) d:
1
3.95 (dd, 1H, J4H,5H¼7.9 Hz, J5H,6H¼3.2 Hz, 5-H), 4.98 (br
s, 1H, OH, exchangeable with D2O), 5.53 (d, 1H, J5H,6H
¼
4.4.2. Compound 7b
Yellowish solid (83%), mp 159e161 ꢀC. IR (KBr) nmax 3008,
1632, 1052 cmꢂ1. 1H NMR (DMSO-d6/TMS) d: 4.07 (dd, 1H,
3.2 Hz, 6-H), 7.55 (d, 1H, J4H,5H¼7.9 Hz, 4-H), 9.87 (s, 1H,
CHO). 13C NMR (DMSO-d6/TMS) d: 62.3, 92.1, 163.3,
172.1, 192.5. MS (FAB) m/z 160 (MHþ). Anal. Calcd for
C5H5NO3S: C, 37.73; H, 3.17; N, 8.80%. Found: C, 37.95;
H, 3.56; N, 8.89%.
J4aH,4H¼8.7 Hz, J4aH,7aH¼3.9 Hz, 4a-H), 5.13 (dd, 1H, J7aH,7H
¼
9.1 Hz, J4aH,7aH¼3.9 Hz, 7a-H), 7.59 (d, 1H, J4aH,4H¼8.7 Hz,
4-H), 7.67 (d, 1H, J7aH,7H¼9.1 Hz, 7-H). 13C NMR (DMSO-
d6/TMS) d: 65.2, 71.9, 158.7, 161.2, 193.2. MS (FAB) m/z 157
(MHþ). Anal. Calcd for C5H4N2O2S: C, 38.46; H, 2.58; N,
17.94%. Found: C, 38.69; H, 2.69; N, 17.76%.
4.3.3. Compound 6a
White solid (81%), mp 112e113 ꢀC. IR (KBr) nmax 3393,
1
3385, 3012, 1713, 1697, 1634 cmꢂ1. H NMR (DMSO-d6/
TMS) d: 3.71 (d, 1H, J1 H,6H¼5.9 Hz, 10H), 4.01 (dd,
4.4.3. Compound 8a
Yellowish solid (91%), mp 152e154 ꢀC. IR (KBr) nmax
0
1H, J4H,5H¼7.8 Hz, J5H,6H¼3.5 Hz, 5-H), 4.97e5.19 (br
s, 2H, 2ꢃOH, exchangeable with D2O), 5.58 (dd, 1H,
3012, 1696, 1634, 1605, 1581, 1455 cmꢂ1
.
1H NMR

L.D.S. Yadav et al. / Tetrahedron 64 (2008) 4246e4253
4251
(DMSO-d6/TMS) d: 4.23 (dd, 1H, J4aH,4H¼8.2 Hz, J4aH,7aH
¼
1H, J8aH,8H¼9.3 Hz, J4aH,8aH¼3.3 Hz, 8a-H), 5.01 (br s, 1H,
OH, exchangeable with D2O), 7.47 (d, 1H, J4aH,4H¼8.9 Hz,
4-H), 7.55 (d, 1H, J7H,8H¼6.8 Hz, 7-H). 13C NMR (DMSO-
d6/TMS) d: 55.9, 70.9, 81.5, 159.5, 161.5, 173.4. MS (FAB)
m/z 171 (MHþ). Anal. Calcd for C6H6N2O4: C, 42.36; H,
3.55; N, 16.47%. Found: C, 42.64; H, 3.38; N, 16.11%.
3.7 Hz, 4a-H), 5.71 (dd, 1H, J7aH,7H¼7.6 Hz, J4aH,7aH¼3.7 Hz,
7a-H), 7.12e7.57 (m, 5Harom), 7.56 (d, 1H, J7aH,7H¼7.6 Hz,
7-H), 7.69 (d, 1H, J4aH,4H¼8.2 Hz, 4-H). 13C NMR (DMSO-
d6/TMS) d: 56.2, 78.3, 121.2, 125.7, 127.7, 130.2, 156.2,
161.3, 172.5. MS (FAB) m/z 216 (MHþ). Anal. Calcd for
C11H9N3O2: C, 61.39; H, 4.22; N, 19.53%. Found: C, 61.03;
H, 4.43; N, 19.37%.
4.5.2. Compound 10b
Yellowish solid (88%), mp 181e183 ꢀC. IR (KBr) nmax
1
3395, 3006, 1639, 1051 cmꢂ1. H NMR (DMSO-d6/TMS) d:
4.4.4. Compound 8b
Yellowish solid (93%), mp 168e171 ꢀC. IR (KBr) nmax
3.87 (dd, 1H, J8aH,8H¼9.2 Hz, J7H,8H¼6.8 Hz, 8-H), 3.99
(dd, 1H, J4aH,4H¼8.9 Hz, J4aH,8aH¼3.3 Hz, 4a-H), 4.81 (dd,
1H, J8aH,8H¼9.2 Hz, J4aH,8aH¼3.3 Hz, 8a-H), 4.99 (br s, 1H,
OH, exchangeable with D2O), 7.44 (d, 1H, J4aH,4H¼8.9 Hz,
4-H), 7.53 (d, 1H, J7H,8H¼6.8 Hz, 7-H). 13C NMR (DMSO-
d6/TMS) d: 56.2, 71.2, 80.9, 160.2, 161.7, 193.4. MS (FAB)
m/z 187 (MHþ). Anal. Calcd for C6H6N2O3S: C, 38.70; H,
3.25; N, 15.05%. Found: C, 38.51; H, 3.36; N, 15.26%.
1
3009, 1631, 1601, 1579, 1449, 1321, 1312, 1057 cmꢂ1. H
NMR (DMSO-d6/TMS) d: 4.19 (dd, 1H, J4aH,4H¼8.2 Hz,
J4aH,7aH¼3.3 Hz, 4a-H), 5.75 (dd, 1H, J7aH,7H¼7.6 Hz,
J4aH,7aH¼3.3 Hz, 7a-H), 7.18e7.61 (m, 5Harom), 7.59 (d, 1H,
J7aH,7H¼7.6 Hz, 7-H), 7.72 (d, 1H, J4aH,4H¼8.2 Hz, 4-H).
13C NMR (DMSO-d6/TMS) d: 55.9, 81.2, 122.5, 125.9,
127.5, 130.5, 156.5, 161.2, 192.7. MS (FAB) m/z 232
(MHþ). Anal. Calcd for C11H9N3OS: C, 57.13; H, 3.92; N,
18.17%. Found: C, 57.38; H, 3.77; N, 17.95%.
4.5.3. Compound 11a
Yellowish solid (92%), mp 133e135 ꢀC. IR (KBr) nmax
4.4.5. Compound 9a
Yellowish solid (85%), mp 185e187 ꢀC. IR (KBr) nmax
1
3392, 3003, 1692, 1635 cmꢂ1. H NMR (DMSO-d6/TMS) d:
3.81 (dd, 1H, J4aH,4H¼8.5 Hz, J4aH,8aH¼3.7 Hz, 4a-H), 3.92
(dd, 1H, J8aH,8H¼9.3 Hz, J7H,8H¼6.5 Hz, 8-H), 4.81 (dd, 1H,
J8aH,8H¼9.3 Hz, J4aH,8aH¼3.7 Hz, 8a-H), 4.95 (br s, 1H, OH,
exchangeable with D2O), 7.05e7.61 (m, 5Harom), 7.45 (d,
1H, J4aH,4H¼8.5 Hz, 4-H), 7.55 (d, 1H, J7H,8H¼6.5 Hz, 7-H).
13C NMR (DMSO-d6/TMS) d: 62.3, 70.7, 81.9, 123.4,
127.9, 129.7, 130.6, 160.2, 161.1, 172.9. MS (FAB) m/z 246
(MHþ). Anal. Calcd for C12H11N3O3: C, 58.77; H, 4.52; N,
17.13%. Found: C, 58.49; H, 4.37; N, 17.29%.
1
2998, 1692, 1635 cmꢂ1. H NMR (DMSO-d6/TMS) d: 1.67
(s, 3H, Me), 3.12 (dd, 1H, J4aH,4H¼8.5 Hz, J4aH,8aH¼3.9 Hz,
4a-H), 4.57 (dd, 1H, J8aH,8H¼7.9 Hz, J4aH,8aH¼3.9 Hz,
8a-H), 7.53 (d, 1H, J8aH,8H¼7.9 Hz, 8-H), 7.61 (d, 1H,
J4aH,4H¼8.5 Hz, 4-H). 13C NMR (DMSO-d6/TMS) d: 51.3,
75.2, 159.2, 161.5, 162.7, 163.8, 173.5. MS (FAB) m/z 166
(MHþ). Anal. Calcd for C7H7N3O2: C, 50.91; H, 4.27; N,
25.44%. Found: C, 50.67; H, 4.49; N, 25.32%.
4.4.6. Compound 9b
Yellowish solid (82%), mp 159e161 ꢀC. IR (KBr) nmax
4.5.4. Compound 11b
Yellowish solid (91%), mp 143e145 ꢀC. IR (KBr) nmax
1
3005, 1631, 1055 cmꢂ1. H NMR (DMSO-d6/TMS) d: 1.72
1
3390, 3007, 1631, 1057 cmꢂ1. H NMR (DMSO-d6/TMS) d:
(s, 3H, Me), 3.15 (dd, 1H, J4aH,4H¼8.5 Hz, J4aH,8aH¼3.6 Hz,
4a-H), 4.63 (dd, 1H, J8aH,8H¼7.9 Hz, J4aH,8aH¼3.6 Hz,
8a-H), 7.49 (d, 1H, J8aH,8H¼7.9 Hz, 8-H), 7.60 (d, 1H,
J4aH,4H¼8.5 Hz, 4-H). 13C NMR (DMSO-d6/TMS) d: 51.5,
74.8, 157.9, 160.8, 162.5, 163.2, 192.3. MS (FAB) m/z 182
(MHþ). Anal. Calcd for C7H7N3OS: C, 46.40; H, 3.89; N,
23.19%. Found: C, 46.27; H, 3.95; N, 23.55%.
3.80 (dd, 1H, J4aH,4H¼8.5 Hz, J4aH,8aH¼3.3 Hz, 4a-H), 3.91
(dd, 1H, J8aH,8H¼9.1 Hz, J7H,8H¼6.5 Hz, 8-H), 4.83 (dd, 1H,
J8aH,8H¼1.3 Hz, J4aH,8aH¼3.3 Hz, 8a-H), 4.98 (br s, 1H, OH,
exchangeable with D2O), 7.09e7.58 (m, 5Harom), 7.48 (d,
1H, J4aH,4H¼8.5 Hz, 4-H), 7.56 (d, 1H, J7H,8H¼6.5 Hz, 7-H).
13C NMR (DMSO-d6/TMS) d: 62.7, 71.5, 82.7, 122.5,
123.7, 127.8, 130.1, 159.8, 161.5, 192.8. MS (FAB) m/z 262
(MHþ). Anal. Calcd for C12H11N3O2S: C, 55.16; H, 4.24; N,
16.08%. Found: C, 55.31; H, 4.13; N, 16.37%.
4.5. 1,2-Oxazino- and pyrazino-1,3-oxazin-2-ones(thiones)
10 and 11: general procedure
These were prepared by following the similar procedure as
described above for 7e9, except that in this case 6 (1 mmol)
was used in place of 5 to yield 10 and 11. To obtain analyti-
cally pure sample of compounds 10 and 11, the same proce-
dure was adopted as described for 7e9.
4.6. Furo- and pyrano-1,3-oxazin-2-ones(thiones) 12 and 13:
general procedure
An intimate solvent-free mixture of 1,3-oxazin-2-ones-
(thiones) (2 mmol) 3 and montmorillonite K-10 clay (0.20 g)
was taken in a 20 mL vial and subjected to MW irradiation
at 95 ꢀC for 5e8 min to get the crude product, which was
extracted with ethyl acetate (3ꢃ20 mL). The extract was
filtered, the filtrate was evaporated under reduced pressure
and the residue thus obtained was recrystallized from ethanol
to afford analytically pure sample of 12 or 13.
4.5.1. Compound 10a
Yellowish solid (81%), mp 173e175 ꢀC. IR (KBr) nmax
1
3393, 3008, 1694, 1638 cmꢂ1. H NMR (DMSO-d6/TMS) d:
3.85 (dd, 1H, J8aH,8H¼9.3 Hz, J7H,8H¼6.8 Hz, 8-H), 4.03
(dd, 1H, J4aH,4H¼8.9 Hz, J4aH,8aH¼3.3 Hz, 4a-H), 4.78 (dd,

4252
L.D.S. Yadav et al. / Tetrahedron 64 (2008) 4246e4253
4.6.1. Compound 12a
Yellowish solid (85%), mp 113e114 ꢀC. IR (KBr) nmax
4.7. 4-Amino oxazine-2,6-diones(6-one-2-thiones) 14:
general procedure
1
3392, 3015, 1698, 1633 cmꢂ1. H NMR (DMSO-d6/TMS) d:
3.56 (dd, 1H, J6Ha,Hb¼11.8 Hz, J6Ha,7H¼4.4 Hz, 6-Ha), 3.81
(dd, 1H, J6Ha,Hb¼11.8 Hz, J6Hb,7H¼2.6 Hz, 6-Hb), 3.94 (ddd,
1H, J7H,7Ha¼8.8 Hz, J6Ha,7H¼4.4 Hz, J6Hb,7H¼2.6 Hz, 7-H),
4.19 (dd, 1H, J4aH,4H¼8.1 Hz, J4aH,7aH¼4.2 Hz, 4a-H), 4.92
(dd, 1H, J7H,7Ha¼8.8 Hz, J4aH,7aH¼4.2 Hz, 7a-H), 5.02 (br s,
8.1 Hz, 4-H). 13C NMR (DMSO-d6/TMS) d: 56.5, 71.3,
81.6, 82.7, 162.6, 172.8. MS (FAB) m/z 158 (MHþ). Anal.
Calcd for C6H7NO4: C, 45.86; H, 4.49; N, 8.91%. Found: C,
45.95; H, 4.57; N, 8.73%.
Thoroughly mixed phenylurea (0.272 g, 2 mmol), aldehyde
5 (0.286 g for 5a, 2 mmol), ammonium acetate (0.154 g,
2 mmol) and montmorillonite K-10 clay (0.20 g) were taken
in a 20 mL vial subjected to microwave irradiation at 90 ꢀC
for 9e10 min. After completion of the reaction as indicated
by TLC (hexane/AcOEt, 8:2, v/v), the product was extracted
with dichloromethane (3ꢃ20 mL), the extract was filtered
and the filtrate was evaporated under reduced pressure to leave
the crude product, which was recrystallized from ethanol to
obtain an analytically pure sample of 14 as yellowish needles.
1H, OH, exchangeable with D2O), 7.45 (d, 1H, J4aH,4H
¼
4.6.2. Compound 12b
Yellowish solid (83%), mp 139e141 ꢀC. IR (KBr) nmax
4.7.1. Compound 14a
Yellowish solid (89%), mp 181e182 ꢀC. IR (KBr) nmax
1
1
3395, 3009, 1635, 1053 cmꢂ1. H NMR (DMSO-d6/TMS) d:
3342, 3007, 1691, 1638 cmꢂ1. H NMR (DMSO-d6/TMS) d:
3.55 (dd, 1H, J6Ha,Hb¼12.1 Hz, J6Ha,7H¼4.1 Hz, 6-Ha), 3.76
(dd, 1H, J6Ha,Hb¼12.1 Hz, J6Hb,7H¼2.6 Hz, 6-Hb), 3.88 (ddd,
1H, J7H,7Ha¼8.9 Hz, J6Ha,7H¼4.1 Hz, J6Hb,7H¼2.6 Hz, 7-H),
4.21 (dd, 1H, J4aH,4H¼8.2 Hz, J4aH,7aH¼4.2 Hz, 4a-H), 4.89
(dd, 1H, J7H,7Ha¼8.9 Hz, J4aH,7aH¼4.2 Hz, 7a-H), 4.97 (br s,
1H, OH, exchangeable with D2O), 7.48 (d, 1H,
J4aH,4H¼8.2 Hz, 4-H). 13C NMR (DMSO-d6/TMS) d: 58.2,
70.9, 79.8, 81.8, 163.2, 192.5. MS (FAB) m/z 174 (MHþ).
Anal. Calcd for C6H7NO3S: C, 41.61; H, 4.07; N, 8.09%.
Found: C, 41.39; H, 4.21; N, 7.88%.
2.98e3.12 (br s, 2H, NH, exchangeable with D2O), 4.32 (dd,
1H, J4aH,4H¼8.5 Hz, J4aH,8aH¼2.9 Hz, 4a-H), 4.97 (dd, 1H,
J8aH,8H¼7.3 Hz, J4aH,8aH¼2.9 Hz, 8a-H), 5.78 (m, 1H, 8-H),
7.03e7.51 (m, 5Harom), 7.58 (d, 1H, J4aH,4H¼8.5 Hz, 4-H).
13C NMR (DMSO-d6/TMS) d: 55.8, 76.5, 81.3, 125.1,
128.2, 129.4, 130.7, 161.5, 172.1, 173.4. MS (FAB) m/z 262
(MHþ). Anal. Calcd for C12H11N3O4: C, 55.17; H, 4.24; N,
16.09%. Found: C, 55.39; H, 4.11; N, 16.31%.
4.7.2. Compound 14b
Yellowish solid (93%), mp 168e171 ꢀC. IR (KBr) nmax
1
4.6.3. Compound 13a
Yellowish solid (90%), mp 150e152 ꢀC. IR (KBr) nmax
3347, 3011, 1699, 1631, 1057 cmꢂ1. H NMR (DMSO-d6/
TMS) d: 2.94e3.10 (br s, 2H, NH, exchangeable with D2O),
4.27 (dd, 1H, J4aH,4H¼8.0 Hz, J4aH,8aH¼2.9 Hz, 4a-H), 5.01
(dd, 1H, J8aH,8H¼7.3 Hz, J4aH,8aH¼2.9 Hz, 8a-H), 5.83 (m,
1
3391, 3383, 3013, 1692, 1638 cmꢂ1. H NMR (DMSO-d6/
TMS) d: 3.39 (ddd, 1H, J6Ha,7H¼9.5 Hz, J7H,8H¼9.3 Hz,
J6Hb,7H¼3.8 Hz, 7-H), 3.57 (dd, 1H, J6Ha,Hb¼12.7 Hz, J6Ha,7H
9.5 Hz, 6-Ha), 3.91 (dd, 1H, J6Ha,Hb¼12.7 Hz, J6Hb,7H
¼
1H, 8-H), 7.12e7.65 (m, 5Harom), 7.53 (d, 1H, J4aH,4H
¼
¼
8.0 Hz, 4-H). 13C NMR (DMSO-d6/TMS) d: 55.2, 75.9,
82.5, 126.2, 127.9, 128.8, 130.1, 162.7, 172.7, 193.2. MS
(FAB) m/z 278 (MHþ). Anal. Calcd for C12H11N3O3S:
C, 51.98; H, 4.00; N, 15.15%. Found: C, 51.67; H, 4.29;
N, 15.21%.
3.8 Hz, 6-Hb), 4.05 (dd, 1H, J7H,8H¼9.3 Hz, J8H,8aH¼8.8 Hz,
8-H), 4.18 (dd, 1H, J4aH,4H¼8.1 Hz, J4aH,8aH¼3.2 Hz, 4a-H),
4.25 (dd, 1H, J8H,8Ha¼8.8 Hz, J4aH,8aH¼3.2 Hz, 8a-H),
4.95e5.18 (br s, 2H, 2ꢃOH, exchangeable with D2O), 7.47
(d, 1H, J4aH,4H¼8.1 Hz, 4-H). 13C NMR (DMSO-d6/TMS) d:
65.5, 71.2, 76.3, 81.5, 82.9, 163.0, 172.5. MS (FAB) m/z
188 (MHþ). Anal. Calcd for C7H9NO5: C, 44.92; H, 4.85;
N, 7.48%. Found: C, 45.21; H, 4.68; N, 7.24%.
4.8. Oxazine-2,6-diones(6-one-2-thiones) 16
Thoroughly mixed aldehyde 5 (0.286 g for 5a, 2 mmol),
semicarbazide hydrochloride (0.223 g, 2 mmol), sodium
acetate (0.164 g, 2 mmol) and montmorillonite K-10 clay
(0.10 g) were taken in a 20 mL vial and subjected to micro-
wave irradiation at 90 ꢀC for 8e11 min to afford crude prod-
uct, which was extracted with dichloromethane (3320 mL).
The extract was filtered and the filtrate was evaporated under
reduced pressure to leave the product, which was recrystal-
lized from ethanol to obtain analytically pure sample of 16.
4.6.4. Compound 13b
Yellowish solid (87%), mp 173e175 ꢀC. IR (KBr) nmax
1
3393, 3382, 3009, 1633, 1058 cmꢂ1. H NMR (DMSO-d6/
TMS) d: 3.43 (ddd, 1H, J6Ha,7H¼9.3 Hz, J7H,8H¼9.0 Hz,
J6Hb,7H¼3.8 Hz, 7-H), 3.61 (dd, 1H, J6Ha,Hb¼12.4 Hz, J6Ha,7H
¼
¼
9.3 Hz, 6-Ha), 3.89 (dd, 1H, J6Ha,Hb¼12.4 Hz, J6Hb,7H
3.8 Hz, 6-Hb), 4.06 (dd, 1H, J7H,8H¼9.0 Hz, J8H,8Ha¼8.8 Hz,
8-H), 4.14 (dd, 1H, J4aH,4H¼8.1 Hz, J4aH,8aH¼3.2 Hz, 4a-H),
4.24 (dd, 1H, J8H,8aH¼8.8 Hz, J4aH,8aH¼3.2 Hz, 8a-H),
4.93e5.19 (br s, 2H, 2ꢃOH, exchangeable with D2O), 7.51
(d, 1H, J4aH,4H¼8.2 Hz, 4-H). 13C NMR (DMSO-d6/TMS) d:
65.2, 71.3, 76.5, 81.4, 83.1, 162.8, 193.2. MS (FAB) m/z
204 (MHþ). Anal. Calcd for C7H9NO4S: C, 41.37; H, 4.46;
N, 6.89%. Found: C, 41.55; H, 4.29; N, 6.63%.
4.8.1. Compound 16a
Yellowish solid (91%), mp 163e165 ꢀC. IR (KBr) nmax
1
2995, 1695, 1638 cmꢂ1. H NMR (DMSO-d6/TMS) d: 4.32
(d, 2H, J4,4aH(J8,8aH)¼8.2 Hz, 4a-H, 8a-H), 7.56 (d, 2H,
J
4,4aH(J8,8aH)¼8.2 Hz, 4-H, 8-H). 13C NMR (DMSO-d6/
TMS) d: 71.5, 162.3, 172.5. MS (FAB) m/z 169 (MHþ).

L.D.S. Yadav et al. / Tetrahedron 64 (2008) 4246e4253
4253
8. Kobayashi, M.; Kitazawa, M.; Sotio, T.; Yamamoto, R.; Harada, H.
Yakugaku Zasshi 1984, 104, 659e679; Chem. Abstr. 1985, 102, 6344m.
9. Testa, E.; Fontanella, L.; Cristiani, G.; Gallo, G. J. Org. Chem. 1959, 24,
1928e1936.
Anal. Calcd for C6H4N2O4: C, 42.87; H, 2.40; N, 16.66%.
Found: C, 42.61; H, 2.61; N, 16.49%.
10. (a) Raynaud, G.; Sergant, M.; Douzon, C.; Fauran, C. U.S. 3,821,215,
1974; Chem. Abstr. 1975, 82, 49951r; (b) Vrouenraets, S. M.; Wit,
W. F.; van Tongeren, J.; Lange, J. M. Expert Opin. Pharmacother. 2007,
8, 851e871.
4.8.2. Compound 16b
Yellowish solid (90%), mp 175e177 ꢀC. IR (KBr) nmax
1
3002, 1693, 1633, 1053 cmꢂ1. H NMR (DMSO-d6/TMS) d:
3.98 (dd, 1H, J4H,4aH¼7.9 Hz, J4aH,8aH¼5.5 Hz, 4a-H), 4.05
(d, 1H, J8H,8aH¼6.3 Hz, 8-H), 4.19 (dd, 1H, J8H,8aH¼6.3 Hz,
J4aH,8aH¼3.1 Hz, 8a-H), 7.51 (d, 1H, J4,4aH¼7.9 Hz, 4-H).
13C NMR (DMSO-d6/TMS) d: 65.5, 71.9, 161.9, 172.5,
193.1. MS (FAB) m/z 185 (MHþ). Anal. Calcd for
C6H4N2O3S: C, 39.13; H, 2.19; N, 15.21%. Found: C,
39.38; H, 2.12; N, 15.43%.
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Acknowledgements
We sincerely thank the CSIR, New Delhi, for financial
support. We are also thankful to SAIF, Punjab University,
Chandigarh, for providing microanalyses and spectra.
18. Thomas, K. Tetrahedron 2005, 61, 3091e3096.
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