Efficient diverse approach for quinoxaline-derived glycosylated and morphinylated analogs

Article abstract of DOI:10.1002/jhet.496

Sulfanyl-glycosides have been synthesized by reaction of 2,3-dimercaptoquinoxaline (1) with acetohalo sugars in presence of base to give the thioglycosides-derived quinoxalines 5-7 and 9. Similarly, the acyclic analogs 23-26 were prepared by coupling of 1 with different acyclo-alkylating agents. The preparation of 3-morpholinyl-quinoxalines 10 and 11 allowed the synthesis of 3-glycosylsulfanyl-2-morpholinyl-quinoxalines 12-14 and 17 as well as the acyclic analogs 27-29. Microwave irradiation of the reactants turned out to be preferred over the conventional method for achieving the synthetic goals. This study made an available venue to the synthesis of diverse quinoxaline derivatives.

Full text of DOI:10.1002/jhet.496

50
Efficient Diverse Approach for Quinoxaline-Derived Glycosylated
and Morphinylated Analogs
Vol 48
Razika Beldi,a Kamal F. Atta,b Sallah Aboul-Ela,b and El Sayed H. El Ashryb*
aDepartment of Chemistry, Faculty of Science, Es-Senia University, Oran, Algeria
bDepartment of Chemistry, Faculty of Science, Alexandria University, Alexandria, Egypt
*E-mail: eelashry60@hotmail.com
Received December 10, 2009
DOI 10.1002/jhet.496
Published online 31 August 2010 in Wiley Online Library (wileyonlinelibrary.com).
Sulfanyl-glycosides have been synthesized by reaction of 2,3-dimercaptoquinoxaline (1) with aceto-
halo sugars in presence of base to give the thioglycosides-derived quinoxalines 5–7 and 9. Similarly,
the acyclic analogs 23–26 were prepared by coupling of 1 with different acyclo-alkylating agents. The
preparation of 3-morpholinyl-quinoxalines 10 and 11 allowed the synthesis of 3-glycosylsulfanyl-2-mor-
pholinyl-quinoxalines 12–14 and 17 as well as the acyclic analogs 27–29. Microwave irradiation of the
reactants turned out to be preferred over the conventional method for achieving the synthetic goals.
This study made an available venue to the synthesis of diverse quinoxaline derivatives.
J. Heterocyclic Chem., 48, 50 (2011).
INTRODUCTION
Efforts in our laboratory has been devoted to develop
efficient protocols for the preparation of a diverse col-
lection of substituted heterocyclic scaffolds [8,9]. Con-
tinuing our interest in the chemistry of quinoxalines [10]
and thioglycosides [1–4,11], as well as MAOS, we
report herein the synthesis of divalent sulfanyl-glyco-
sides–derived quinoxaline and their acyclic analogs.
Selective monomorpholinylation of 2,3-dimercapto-qui-
noxaline allowed diverse reactions on the other thiol
group whereby glycosylation and acyclo-alkylation reac-
tions have been investigated, which have represented an
efficient protocol for developing a library of compounds
having the quinoxaline ring.
The wide use of sulfanyl(thio)-glycosides as biologi-
cal inhibitors [1], inducers, and ligands for affinity chro-
matography of carbohydrate processing enzymes and
proteins has attracted much attention toward their syn-
thesis [2–4]. Recently, glycosylthio heterocycles have
proved their success as glycosyl donors as well as gly-
cosyl acceptors as a result of their variable stability
under variety of conditions. Moreover, their use as
acceptors and subsequently as donors increased their
value in the field of oligosaccharide synthesis [2].
Functionalized quinoxaline systems are an important
class of nitrogen-containing heterocycles possessing a
broad spectrum of biological activities [5]. Benefits
from the emerging technology of microwave (MW)-
assisted organic synthesis (MAOS) has had a profound
impact on the synthesis of organic compounds [6,7] and
on developing the combinatorial chemistry to exploit a
high degree of molecular diversity.
RESULT AND DISCUSSION
The 2,3-dimercaptoquinoxalinedithiol [12] (1) has
served as a key starting material. It was prepared from
the condensation of oxalic acid and o-phenylenediamine
C
V
2010 HeteroCorporation

January 2011
Efficient Diverse Approach for Quinoxaline-Derived
Glycosylated and Morphinylated Analogs
51
Scheme 1. Reagents and conditions: (A) NaOH, DMF, and MWI. (B)
K2CO3, DMF, and MWI.
presence of base gave the respective bisthioglycoside 9.
Alternatively, the sodium quinoxaline 2,3-thiolate from
1 can be reacted with the acetobromo sugars to give 9
in almost the same yield (Scheme 1).
1
The H and 13C NMR spectra of compound 9 con-
firmed the assigned structure and showed also the equiv-
alent nature of the two sugar moieties. The anomeric
proton H-10a was assigned to the doublet at d 5.97 with
0
0
J1 a,2 a ¼ 10.7 Hz indicating a biaxial orientation of H-
10a and H-20a. H-10a proton was correlated with the tri-
plet of H-20a at d 5.20 and their respective carbons were
assigned at d 80.6 and 69.3, respectively. The H-20b pro-
tons were resonated at d 5.10 as doublet of doublet with
0
0
J2 b,1 b ¼ 7.6 Hz and correlated with the doublet of H-
10b at d 4.47 and the doublet of doublet of H-30b at d
4.92, respectively. The anomeric carbon C-10b appeared
at d 101.2 confirmed that the anomeric proton is axial.
Morpholinylation of 2,3-dichloroquinoxaline gave 2-
chloro-3-morpholinyl-quinoxaline (11) whose coupling
with 2,3,4,6-tetra-O-acetyl-b-D-gluco- and b-D-galacto-
pyranosyl isothiouronium bromide 15 and 16 [14,15],
prepared from acetylated sugar bromide 2 and 3 and thi-
ourea under MW [15], in presence of Et3N in acetoni-
trile afforded the respective sulfanylglycosides 3-mor-
pholinyl-2-(20,30,40,60-tetra-O-acetyl-1-b-sulfanyl-D-glu-
copyranosyl)quinoxaline (12) and 3-morpholinyl-2-
(20,30,40,60-tetra-O-acetyl-1-b-sulfanyl-D-galactopyrano-
syl) quinoxaline (13). Alternatively, compounds 12
and 13 were obtained from the reaction of 2-mercapto-
3-morpholinyl-quinoxaline (10) with the respective
sugar bromide 2 and 3 in presence of potassium car-
bonate in DMF. Also 12–14 were synthesized from the
coupling of the sodium salt of 10 with acetobromo sug-
and the product was converted to 2,3-dichloroquinoxa-
line whose reaction with thiourea gave the isothiouro-
nium salt whose treatment with alka1i gave 1. Reaction
of 1 with 2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl bro-
mide (2) in presence of aqueous sodium hydroxide or
potassium carbonate gave 2,3-bis(20,30,40,60-tetra-O-ace-
tyl-b-D-glucopyranosyl-thio)quinoxaline (5) [13]. Alter-
natively, 5 was recently prepared from the reaction of
2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl isothiouronium
salt [14,15] with 2,3-dichloroquinoxaline in presence of
triethylamine in acetonitrile. Similarly, 2,3-bis(glycosyl-
thio)quinoxaline 6 and 7 were prepared from the reac-
tion of the sodium salt of 1 with 2,3,4,6-tetra-O-acetyl-
a-D-galactopyranosyl bromide (3) and 2-acetamido-
3,4,6-tri-O-acetyl-2-deoxy-a-D-glucopyranosyl chloride
(4), respectively (Scheme 1).
1
ars 2–4. The H NMR and 13C NMR spectra confirmed
the assigned structures. Thus, H-10 in 12 appeared at d
0
0
6.04 as a doublet with J1 ,2 ¼ 10.7 Hz, confirming the
b-configuration. Further correlation of protons and car-
bons in a similar manner to that used above led to a
complete assignment of protons and carbons.
1
Examination of the H NMR and 13C NMR spectra of
6 indicated the chemical equivalence of protons and car-
bons of the two sugar moieties. The assignments were
based on correlation experiments. Thus, the b-linkage of
the thioglycosidic bond was confirmed from the value of
Under the same reaction conditions, acetobromo lac-
tose 8 was coupled with 10 to give the sulfanylglycoside
17. The doublet corresponding to the anomeric protons
H-10a and H-10b were resonated at d 6.02 and 4.48,
0
0
coupling constant J1 ,2 (10.7 Hz) in the doublet of the
anomeric proton at d 6.03. The triplet of H-20 at d 5.52
can be correlated with the corresponding carbon at d
67.5. The doublet of doublet of H-30 resonated at d 5.24
0
0
respectively, where J1 a,2 a ¼ 10.7 Hz that confirmed the
b-configuration for the newly formed thioglycoside link-
age. Both H-10a and H-10b were correlated with their
carbons at d 80.7 and 101.3, respectively (Scheme 2).
The acyclic analogs 23–26 were synthesized from the
coupling of sodium salt of 2,3-quinoxalinedithiol (1), as
nucleophilic source, with a number of acyclo-alkylating
agents. Alternatively, the reaction of 1 with the alkyl-
ating agents has been done in presence of potassium car-
bonate. Thus, 1 was coupled with (6)epichlorohydrin to
give 2,3-bis(20,30-epoxy-propyl-10-thio)quinoxaline (24),
and correlated with H-40 at d 5.52 (J3 ,4 ¼ 3.8 Hz).The
latter correlated with the multiplet of H-50 and its car-
bon. Both of H-60 and H-600 were resonated as doublet
of doublet at d 4.05 and 4.14, respectively, whereas its
carbon was assigned at d 61.7.
0
0
Furthermore reaction of 2,3-dimercaptoquinoxaline
(1) with 2,3,6-tri-O-acetyl-4-O-(2,3,4,6-tetra-O-acetyl-b-
D-galactopyranosyl)-a-D-glucopyranosyl bromide (8) in
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DOI 10.1002/jhet

52
R. Beldi, K. F. Atta, S. Aboul-Ela, and E. S. H. El Ashry
Vol 48
Scheme 2. Reagents and conditions: (A) NaOH, DMF, and MWI. (B)
K2CO3, DMF, and MWI. (C) Et3N, MeCN, and MWI.
recorded on Jeol spectrometer (500 MHz). The chemical shifts
are expressed on the d-scale using Me4Si as a standard, and
coupling-constant values are given in Hz. The assignments of
1H NMR spectra were based on the chemical shift correlation
DQFCOSY spectra, while the assignment of 13C NMR spectra
were based on heteronuclear multiple quantum coherence
experiments. Glycosyl protons and carbons are identified by
‘‘prime.’’ TLC was performed on Merck Silica Gel 1B-F with
detection by charring in sulfuric acid (5%) and by UV light.
The MW irradiation was done in a closed Teflon cylindrical
vessel that was placed at the center of rotating plate inside the
oven EM-230 M (1200 watt output power). The vessels were
supported in a frame for safety. Microanalyses were performed
in the Microanalysis Unit at Cairo University.
2,3-Dimercaptoquinoxaline (1). A mixture of o-phenylene-
diamine (0.1 g, 0.92 mmol), oxalic acid (0.08 g, 0.92 mmol)
in HCl (4N, 2 mL) was irradiated for 2 min. The product was
dissolved in alkali solution (7 mL, 10%) followed by neutrali-
zation with dilute HCl to give quinoxaline-2,3-dione. A mix-
ture of quinoxaline-2,3-dione (0.1 g, 0.5 mmol), bentonite (0.1
g), and phosphorus oxychloride (2 mL) was subjected to MW
irradiation for 4 min. The reaction mixture was poured onto
crushed ice. The precipitate was washed with water succes-
sively and recrystallized from ethanol to give 2,3-dichloroqui-
noxaline (90% yield). A solution of the later (0.2 g, 1 mmol)
in ethanol (3 mL) was treated with thiourea (0.2 g, 2.6 mmol)
and then irradiated for 4 min. The solvent was evaporated and
2,3-O-isopropylidene-1-O-(4-toluenesulfonyl)glycerol to
give 25 and allyl bromide to give 26. The spectral anal-
ysis confirmed the involvement of both of the two sulfur
atoms in the alkylation.
The 3-morpholinyl-quinoxaline-2-thiol (10) has been
utilized for the synthesis of the acyclic derivatives 27–
29 by the alkylation with 19, 20, and 22 in the presence
of base (Scheme 3). The S-alkylated derivatives 27 and
28 are potential precursors for modifications, via open-
ing of the dioxalane or epoxide ring, thus provide acy-
clonucleoside analogs [15,16].
Scheme 3. Reagents and conditions: (A) NaOH, DMF, and MWI. (B)
K2CO3, DMF, and MWI.
When the above reactions were done under MW con-
ditions, the same products were obtained but in higher
yield and in shorter reaction times; although a domestic
MW oven was used, it indicated the successful approach
for their synthesis (Table 1). Thus, mild conditions and
relatively clean reactions indicating that the MW
method has advantages over the conventional processes.
CONCLUSION
In conclusion, diversity of functionalized quinoxalines
with glycosyl, morpholinyl, alkyl, and hydroxyalkyl
moeties have been prepared. The synthesis of the sulfa-
nylglycosides-derived quinoxalines was achieved by the
reaction of 2,3-dimercaptoquinoxaline with acetohalo-
geno sugars. The 2-mercapto-3-morpholinyl-quinoxaline
became readily available from 2,3-dichloroquinoxaline,
served as a good precursor for providing various S-alky-
lated and glycosylated products, which are of potential
biological activity.
EXPERIMENTAL
Melting points were determined on a Mel-Temp apparatus
and are uncorrected. 1H NMR and 13C NMR spectra were
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2011
Efficient Diverse Approach for Quinoxaline-Derived
Glycosylated and Morphinylated Analogs
53
Table 1
Comparison of the results obtained from conventional method (CM) and microwave (MW) method.
Time
Yield (%)
Compound
Reagent
CM (hr)
MW (min)
CM
MW
Mp (ꢀC) found/literature
172, 169–170 [13]
5
A
B
A
B
A
B
A
B
A
B
C
A
B
C
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
A
B
3
4
6
6
3
5
5
7
5
8
5
7
7
8
6
8
6
7
3
7
4
4
5
4
4
5
6
7
7
8
4
6
4
4
4
5
4
4
6
6
3
4
4
5
6
4
4
6
4
5
2
3
3
3
2
3
2
3
4
4
6
6
3
5
60
70
69
60
50
44
72
64
61
73
57
60
75
53
65
57
70
63
75
75
56
46
67
65
50
61
69
63
58
47
50
43
82
82
81
70
69
59
85
84
76
85
70
71
84
64
78
74
85
79
91
86
65
63
86
77
63
75
77
80
66
58
61
52
6
7
196–198
189–190, 192–194 [14]
150–151
9
12
160–162
13
64–66
14
17
23
24
25
26
27
28
29
177–178
199–200
127–129, 134–135 [5]
Syrup
Syrup
82–83
Syrup
112–114
Syrup
0
0
0
the remaining solid was dissolved in aqueous sodium hydrox-
ide, then precipitated with dilute HCl. The product was filtered
off and dried to give 1 in 93% yield, mp 298–300ꢀC, lit. mp
295–298ꢀC [12].
H-3 ), 6.09 (d, 2H, J1 ,2 ¼ 10.3 Hz, 2 ꢁ H-10), 7.45–7.67,
7.80–7.95 (2m, 4H, Ar-H).
2,3-Bis(20,30,40,60-tetra-O-Acetyl-b-D-galactopyranosyl-sul-
fanyl)quinoxaline (6). This compound was recrystallized
from ethanol. 1H NMR (CDCl3): d 1.87, 2.01, 2.03, 2.18 (4s,
General procedure for the glycosylation or alkylation of
2,3-dimercaptoquinoxaline.
0
0
00
Method A. A solution of 1
24H, 8 ꢁ CH3CO), 4.05 (dd, 1 H, J6 ,5 ¼ 6.8 Hz, J6 ,6 ¼ 11.4
0
0
0
0
0
(0.2 g, 1 mmol) in aqueous sodium hydroxide (0.09 g in 4
mL) was evaporated to dryness. The resulting salt was dis-
solved in DMF (3 mL), treated with the glycosylating or alkyl-
ating agents and stirred. The mixture was poured onto ice
water, then filtered off.
Hz, H-60), 4.14 (dd, 2H, J6 ,5 ¼ 6.1 Hz, J6 ,6 ¼ 11.4 Hz, 2 ꢁ
H-600), 4.20–4.22 (m, 2H, 2 ꢁ H-50), 4.66 (dd, 2H, J6 ,5 ¼ 6.1
0
0
Hz, J6 ,6 ¼ 11.4 Hz, 2 ꢁ H-60), 5.24 (dd, 2H, J3 ,2 ¼ 9.9 Hz,
0
00
0
0
J4 ,3 ¼ 3.0 Hz, 2 ꢁ H-30), 5.52 (2t, 4H, J2 ,3 ¼ 9.9 Hz, J4 ,3
0
0
0
0
0
0
¼ 3.0 Hz, 2 ꢁ H-20, 2 ꢁ H-40), 6.03 (d, 2H, J1 ,2 ¼ 10.7 Hz,
2 ꢁ H-10), 7.65–7.67, 7.90–7.92 (2m, 4H, Ar-H); 13C NMR
(CDCl3): d 20.7, 20.9 (8 ꢁ CH3CO), 61.7 (2 ꢁ C-60), 66.4 (2
ꢁ C-40), 67.5 (2 ꢁ C-20), 72.2 (2 ꢁ C-30), 75.1 (2 ꢁ C-50),
81.3 (2 ꢁ C-10), 127.8, 129.3 (C-Ar), 140.2 (2 ꢁ C¼¼N), 151.0
(2 ꢁ CAS), 169.6, 170.2, 170.49, 170.5 (8 ꢁ CO). Anal.
Calcd. for C36H42N2O18S2 (854.85): C, 50.58; H, 4.95; N,
3.28; S, 7.50. Found: C, 50.64; H, 4.56; N, 3.24; S, 7.78.
2,3-Bis(20-acetamido-20-deoxy-30,40,60-tri-O-acetyl-b-gluco-
pyranosyl-sulfanyl)quinoxaline (7). This compound was
recrystallized from ethanol. 1H NMR (CDCl3-D2O): d 1.80,
1.89, 2.01, 2.04 (4s, 24H, 6 ꢁ CH3CO, 2 ꢁ NHAc), 4.04–4.06
0
0
Method B. A mixture of 1 (0.2 g, 1 mmol) and potassium
carbonate (0.3 g, 2.3 mmol) in DMF (4 mL) was stirred for 2
hr. The corresponding glycosylating or alkylating agents were
added and the stirring was continued. The mixture was poured
onto ice water, then filtered off. For more details, see Table 1.
2,3-Bis(20,30,40,60-tetra-O-Acetyl-b-D-glucopyranosyl-sulfa-
nyl)quinoxaline (5). This compound was recrystallized from
ethanol. 1H NMR (CDCl3): d 1.84, 2.02, 2.03, 2.05 (4s, 24H,
8 ꢁ CH3CO), 4.09 (d, 2H, J6 ,6 ¼ 12.6 Hz, 2 ꢁ H-60), 4.11–
0
00
4.18 (m, 2H, 2 ꢁ H-50), 4.26 (dd, 2H, J6 ,5 ¼ 5.7 Hz, J6 ,6
¼
00
0
00
0
12.6 Hz, 2 ꢁ H-600), 5.15 (dd, 2H, J4 ,3 ¼ 9.2 Hz, J4 ,5 ¼ 9.8
0
0
0
0
Hz, 2 ꢁ H-40), 5.32 (dd, 2H, J2 ,1 ¼ 10.3 Hz, J2 ,3 ¼ 9.2 Hz,
(m, 4H, 2 ꢁ H-50, 2 ꢁ H-60), 4.22 (dd, 2H, J6 ,5 ¼ 3.5 Hz,
0
0
0
0
00
0
2 ꢁ H-20), 5.50 (dd, 2H, J3 ,4 ¼ 9.2 Hz, J3 ,2 ¼ 9.2 Hz, 2 ꢁ
J6 ,6 ¼ 9.2 Hz, 2 ꢁ H-600), 4.31 (dd, 2H, J2 ,1 ¼ 10.8 Hz,
0
0
0
0
00
0
0
0
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DOI 10.1002/jhet

54
R. Beldi, K. F. Atta, S. Aboul-Ela, and E. S. H. El Ashry
Vol 48
J2 ,3 ¼ 9.7 Hz, 2 ꢁ H-20), 5.08 (dd, 2H, J4 ,3 ¼ 9.2 Hz, J4 ,5
mmol), and triethylamine (1 mmol) in acetonitrile (3 mL) was
stirred, then the solvent was evaporated under reduced pressure
to give the same products.
0
0
0
0
0
0
¼ 9.7 Hz, 2 ꢁ H-40), 5.40 (dd, 2H, J3 ,2 ¼ 9.7 Hz, J3 ,4 ¼ 9.2
0
0
0
0
Hz, 2 ꢁ H-30), 6.10 (d, 2H, J1 ,2 ¼ 10.8 Hz, 2 ꢁ H-10), 7.50–
0
0
7.67, 7.90–7.95 (2m, 4H, Ar-H).
3-Morpholinyl-2-(20,30,40,60-tetra-O-acetyl-b-D-glucopyra-
nosyl-sulfanyl)quinoxaline (12). Crystallized from ethanol.
1H NMR (CDCl3): d 1.88, 2.01, 2.03, 2.05 (4s, 12H, 4 ꢁ
CH3CO), 3.29–3.34 and 3.42–3.46 (2m, 4H, 2 ꢁ CH2N),
3.86–3.88 (m, 4H, 2 ꢁ CH2O), 3.99–4.01 (m, 1H, H-50), 4.10
2,3-Bis(20,30,40,60-tetra-O-acetyl-b-D-galactopyranosyl-(1
fi
4)-(20,30,60-tri-O-acetyl-b-D-glucopyranosyl-sulfanyl)-
quinoxaline (9). This compound was recrystallized from
ethanol. 1H NMR (CDCl3): d 1.88, 1.96, 2.01, 2.05, 2.05,
2.06, 2.15 (6s, 42H, 14 ꢁ CH3CO), 3.85–3.89 (m, 6H, 2 ꢁ H-
40a, 2 ꢁ H-50b, H-600b, H-60b), 4.02–4,07, 4.11–4.15 (2m, 6H,
(dd, 1H, J6 ,5 ¼ 2.2 Hz, J6 ,6 ¼ 12.2 Hz, H-60), 4.22 (dd, 1H,
0
0
0
00
J6 ,5 ¼ 5.3 Hz, J6 ,6 ¼ 12.2 Hz, H-600), 5.17 (t, 1H, J4 ,3
¼
00
0
00
0
0
0
2 ꢁ H-60b, 2 ꢁ H-60a, 2 ꢁ H-600a), 4.47 (2d, 4H, J1 b,2 b
¼
9.5 Hz, J4 ,5 ¼ 9.5 Hz, H-40), 5.33 (dd, 1H, J2 ,3 ¼ 9.5 Hz,
0
0
0
0
0
0
10.6 Hz, 2 ꢁ H-10b, 2 ꢁ H-50a), 4.92 (dd, 2H, J3 b,2 b ¼ 8.7
J2 ,1 ¼ 10.7 Hz, H-20), 5.43 (t, 1H, J4 ,3 ¼ 9.5 Hz, J3 ,2 ¼ 9.5
0
0
0
0
0
0
0
0
Hz, J3 b,4 b ¼ 3.0 Hz, 2 ꢁ H-30b), 5.10 (dd, 2H, J2 b,1 b ¼ 10.7
Hz, H-30), 6.04 (d, 1H, J1 ,2 ¼ 10.7 Hz, H-10), 7.57 (2t, 2H, 2
ꢁ Ar-H), 7.84 (2d, 2H, 2 ꢁ Ar-H). 13C NMR (CDCl3): d 20.7
and 20.8 (4 ꢁ CH3CO), 49.9 (2 ꢁ CH2N), 62.1 (C-60), 66.7 (2
ꢁ CH2O), 68.6 (C-40), 69.2 (C-50), 74.4 (C-20), 76.3 (C-30),
80.7 (C-10), 127.5, 127.6, 128.9, 139.2, 139.2 (C-Ar), 148.2,
153.6 (2 ꢁ C¼¼N), 169.6, 170.3, 170.7 (4 ꢁ CO). Anal. Calcd.
for C26H31N3O10S (577.60): C, 54.06; H, 5.40; N, 7.27; S, 5.5.
Found: C, 54.30; H, 5.33; N, 6.91; S, 5.20.
0
0
0
0
0
0
Hz, J2 b,3 b ¼ 8.4 Hz, 2 ꢁ H-20b), 5.20 (t, 2H, J2 a,3 a ¼ 9.9
0
0
0
Hz, 2 ꢁ 0 H-20a), 5.34–5.39 (m, 4H, 2 ꢁ H-30a, 2 ꢁ H-40b),
5.97 (d, 2H, J1 a,2 a ¼ 10.7 Hz, 2 ꢁ H-10a), 7.63–7.65, 7.86–
7.88 (2m, 4H, Ar-H); 13C NMR (CDCl3): d 20.8, 20.9 (14 ꢁ
CH3), 60.9 (2 ꢁ C-60b), 62.3 (2 ꢁ C-60a), 66.6 (2 ꢁ C-40b),
69.1 (2 ꢁ C-20b), 69.3 (2 ꢁ C-20a), 70.8 (2 ꢁ C-50b), 71.1 (2
ꢁ C-30b), 74.1 (2 ꢁ C-30a), 76.4 (2 ꢁ C-40a), 80.6 (2 ꢁ C-
10a), 101.2 (2 ꢁ C-10b), 128.0, 129.3,140.1 (C-Ar), 140.1
(C¼¼N), 150.9 (2 ꢁ CAS), 169.8, 167.9,170.3, 170.4, 170.5
(14 ꢁ CO). Anal. Calcd. for C60H74N2O34S2 (1431.35): C,
50.35; H, 5.21; N, 1.96; S, 4.48. Found: C, 50.15; H, 5.54; N,
1.98; S, 4.70.
0
0
3-Morpholinyl-2-(20,30,40,60-tetra-O-acetyl-b-1-sulfany-D-
galactopyranosyl)quinoxaline (13). Purified by flash column
chromatography using hexane–ethylacetate (H/E 4/1), 1H
NMR (CDCl3): d 1.86, 2.00, 2.01, 2.17 (4s, 12H, 4 ꢁ
CH3CO), 3.30–3.35 (m, 2H, CH2N), 3.43–4.48 (m, 2H,
CH2N), 3.86–3.88 (m, 4H, 2 ꢁ CH2O), 4.05–4.08 (m, 1H, H-
2-Mercapto-3-morpholin-1-yl-quinoxaline (10).
Conven-
tional method. A solution of 2,3-dichloroquinoxaline (0.1 g,
0.5 mmol) in DMF (2 mL) was treated with morpholine (0.05
mL, 0.6 mmol) and stirred for 2 hr. The mixture was poured
onto ice water, filtered off, and recrystallized from ethanol to
give 2-chloro-3-morpholinyl-quinoxaline (11). A mixture of 11
(0.5 g, 2 mmol), thiourea (0.18 g, 2.4 mmol) in ethanol (5 mL)
was heated under reflux for 2 hr. The solvent was evaporated
under reduced pressure. The residue was dissolved in sodium
hydroxide solution (9 mL, 8%), then neutralized with dilute
HCl. The solid that separated was recrystallized from ethanol.
MWI method. A solution of 2,3-dichloroquinoxaline (0.1 g,
0.5 mmol) in DMF (2 mL) was treated with morpholine (0.05
mL, 0.6 mmol) was irradiated for 2 min, then processed as
50), 4.15 (dd, 1H, J2 ,1 ¼ 11.5 Hz, J2 ,3 ¼ 10.7 Hz, H-20), 4.23
0
0
0
0
(dd, 1H, J6 ,5 ¼ 6.1 Hz, J6 ,6 ¼ 12.2 Hz, H-60), 5.27 (dd, 1H,
0
0
0
00
J6 ,5 ¼ 6.1 Hz, J6 ,6 ¼ 12.2 Hz, H-600), 5.54 (dd, 2H, J3 ,2
¼
00
0
00
0
0
0
10.7 Hz, J3 ,4 ¼ 3.8 Hz, H-30, H-40), 6.05 (d, 1H, J1 ,2 ¼ 11.4
Hz, H-10), 7.31, 7.82 (4H, Ar-H). 13C NMR (CDCl3): d 20.7,
20.7, 20.8, 20.9 (4 ꢁ CH3CO), 50.0 (CH2N), 61.6 (C-60), 66.7
(C-40, CH2O), 67.6 (C-20), 72.4 (C-30), 75.0 (C-50), 81.0 (C-10),
127.5, 127.6, 128.9, 139.2, 139.24 (C-Ar), 148.4 153.6 (2 ꢁ
C¼¼N), 169.8, 170.2, 170.4, 170.5 (4 ꢁ CO). Anal. Calcd. for
C26H31N3O10S (577.60): C, 54.06; H, 5.40; N, 7.27; S, 5.5.
Found: C, 54.20; H, 5.41; N, 7.34; S, 5.30.
0
0
0
0
2-(20-Acetamido-20-deoxy-30,40,60-tri-O-acetyl-b-1-sulfanyl-D-
glucopyranosyl)-3-morpholin-1-yl-quinoxaline (14). Recry-
stallized from ethanol as yellow crystals. H NMR (CDCl3): d
1
1
above, it gave the same product 11. H NMR (CDCl3): d 3.58
(t, 4H, 2 ꢁ CH2N), 3.92 (t, 4H, 2 ꢁ CH2O), 7.51–7.83 (4H,
Ar-H). A mixture of 11 (0.5 g, 2 mmol), thiourea (0.18 g, 2.4
mmol) in ethanol (5 mL) was irradiation with MW for 2 min,
then processed as above to give the product 10 (88% yield),
mp 180–182ꢀC. 1H NMR (CDCl3): d ¼ 3.89 (d, 4H, 2 ꢁ
CH2N), 3.90 (d, 4H, 2 ꢁ CH2O), 7.35–7.67 (m, 4H, Ar-H),
12.21 (s, 1H, SH).
General procedure for the alkylation of 2-mercapto-3-
morpholin-1-yl-quinoxaline. Method A. 2-Mercapto-3-mor-
pholinyl-quinoxaline (10) (0.1 g, 0.4 mmol) was dissolved in
aqueous sodium hydroxide (0.018 g, 3 mL), then water was
evaporated to dryness. The residue was dissolved in DMF (3
mL), then stirred with the appropriate alkylating agent 2–4.
The mixture was poured onto ice water and the product that
separated out was purified.
1.83, 1.93, 2.06, 2.07 (4s, 4H, 4 ꢁ CH3CO), 3.31–3.36, 3.43–
3.47 (2m, 4H, 2 ꢁ CH2N), 3.88–3.89 (m, 5H, H-50, 2 ꢁ
CH2O), 4.10 (bdd, 1H, J6 ,6 ¼ 12.2 Hz, H-60), 4.20 (dd, 1H,
0
00
J6 ,6 ¼ 12.2 Hz, J6 ,5 ¼ 5.3 Hz, H-600), 4.52 (dd, 1H, J2 ,1
¼
00
0
00
0
0
0
10.7 Hz, J2 ,3 ¼ 9.9 Hz, H-20), 5.19 (dd, 1H, J4 ,3 ¼ 10.7 Hz,
0
0
0
0
J4 ,5 ¼ 19.1 Hz, H-40), 5.26 (dd, 1H, J3 ,2 ¼ 9.9 Hz, J3 ,4
¼
0
0
0
0
0
0
10.7 Hz, H-30), 5.85 (d, 1H, J ¼ 9.1 D2O exchangeable, JNH,2
0
¼ 9.1 Hz, NH), 5.94 (d, 1H, J1 ,2 ¼ 10.7 Hz, H-10), 7.53–
7.60, 7.81–7.83 (2m, 4H, Ar-H). 13C NMR (CDCl3): d 20.7,
20.9 (4 ꢁ OCOCH3), 22.8 (NCOCH3), 50.0 (2 ꢁ CH2N), 53.0
(C-2), 62.3 (C-60), 66.7 (2 ꢁ CH2), 68.5 (C-5), 72.1 (C-4),
77.9 (C-3), 81.4 (C-10), 127.1, 127.7, 128.9, 138.9, 139.2 (6 ꢁ
C-Ar), 149.5, 153.7, (2 ꢁ C¼¼N), 169.4, 170.1, 170.9, 171.5 (4
ꢁ CO). Anal. Calcd. for C26H32N4O9S (576.61): C, 54.16; H,
5.59; N, 9.72; S, 5.56. Found: C, 54.30; H, 5.41; N, 10.01; S,
5.30.
0
0
Method B. A mixture of 10 (0.1 g, 0.4 mmol), potassium car-
bonate (0.07 g, 0.5 mmol) in DMF (3 mL) was stirred for 2 hr at
room temperature, then treated with the appropriate alkylating
agent 2–4. Stirring was continued, then processed as above.
Method C. A mixture of 2-chloro-3-morpholinyl-quinoxa-
line (0.2 g, 0.8 mmol), sugar isothiouronium salt 15 and 16 (1
3-Morpholinyl-2-(20,30,40,60-tetra-O-acetyl-b-D-galactopyr-
anosyl-(1 fi 4)-(20,30,40,60-tetra-O-acetyl-b-1-sulfanyl-D-glu-
copyranosyl)quinoxaline (17). Recrystallized from ethanol.
1H NMR (CDCl3): d 1.86, 1.96, 2.00, 2.07, 2.07, 2.16 (6s,
21H, 7 ꢁ CH3CO), 3.31–3.34 (m, 2H, CH2N), 3.40–3.43 (m,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2011
Efficient Diverse Approach for Quinoxaline-Derived
Glycosylated and Morphinylated Analogs
55
2H, CH2N), 3.82–3.93 (m, 7H, 2 ꢁ CH2O, H-20b, H-60a, H-
CH2N), 66.8 (2 ꢁ CH2O), 68.9 (C-30), 74.7 (C-20), 109.7
(CH3C), 127.20, 127.37, 127.47, 128.29, 138.72, 139.22 (C-
Ar), 150, 153.67 (2 ꢁ C¼¼N). Anal. Calcd. for C18H23N3O3S
(361.46): C, 59.81; H, 6.41; N, 11.62; S, 8.86. Found C,
59.58; H, 6.72; N, 11.41; S, 9.01.
60b), 4.07 (dd, 1H, J6 a,6 a ¼ 11.4 Hz, J6 a,
¼ 5.3 Hz, H-
00
0
00
50a
600a), 4.11 (t, 1H, J5 b,4 b ¼ 3.8 Hz, J5 b,6 b ¼ 6.8 Hz, H-50b),
0
0
0
0
4.16 (dd, 1H, J6 b,5 b ¼ 6.1 Hz, J6 b,6 b ¼ 6.1 Hz, H-600b), 4.43
00
0
00
0
(dd, 1H, J5 a,4 a ¼ 9.9 Hz, J5 a,6 a ¼ 1.5 Hz, H-50a), 4.48 (d,
0
0
0
0
1H, J1 b,2 b ¼ 7.6 Hz, H-10b), 4.96 (dd, 1H, J4 b,3 b ¼ 3.0 Hz,
2-(20,30-Epoxy-propyl-10-sulfanyl)-3-morpholin-1-yl-quinoxa-
line (28). Purified by flash column chromatography using hex-
0
0
0
0
J4 b,5 b ¼ 3.8 Hz, H-40b), 5.16 (dd, 1H, J2 a,1 a ¼ 10.7 Hz,
0
0
0
0
J2 a,3 a ¼ 8.4 Hz, H-20a), 5.25 (dd, 1H, J4 a,3 a ¼ 9.1 Hz, J4 a,5 a
1
0
0
0
0
0
0
ane–ethylacetate (H/E 4/1). H NMR (CDCl3): d 2.51 (dd, 1H,
¼ 9.9 Hz, H-40a), 5.37 (d, 1H, J3 b,4 b ¼ 3.0 Hz, H-30b), 5.40
J3 ,2 ¼ 5.3 Hz, J3 ,3 ¼ 6.1 Hz, H-30), 2.58 (dd, 1H, J3 ,2
¼
0
0
0
0
0
00
00
0
(dd, 1H, J3 a,2 a ¼ 8.4 Hz, J3 a,4 a ¼ 9.1 Hz, H-30a), 6.02 (d,
1.5 Hz, J3 ,3 ¼ 6.1 Hz, H-300), 3.24–3.29 (m, 1H, H-20), 3.84–
0
0
0
0
00
0
1H, J1 a,2 a ¼ 10.7 Hz, H-10a), 7.53–7.59, 7.81–7.85 (2m, 4H,
Ar-H). 13C NMR (CDCl3): d 20.7–20.8 (7 ꢁ CH3CO), 49.9 (2
ꢁ CH2 N), 60.9 (C-60a), 62.4 (C-60b), 66.7 (2 ꢁ CH2O), 69.2
(C-30a), 69.6 (C-20b, C-20a), 70.8 (C-30b), 71.1 (C-40a), 74.3
(C-40b), 76.5 (C-50b, C-50a), 80.7 (C-10a), 101.3 (C-10b),
127.55, 127.57, 127.64, 128.94, 139.20 (C-Ar), 148.3 153.6 (2
0
0
3.86 (m, 4H, 2 ꢁ CH2N), 3.90–3.96 (m, 4H, 2 ꢁ CH2O), 4.38
(dd, 1H, J1 ,1 ¼ 13.7 Hz, J1 ,2 ¼ 4.6 Hz, H-10), 5.2 (dd, 1H,
0
00
0
0
J1 ,1 ¼ 13.7 Hz, J1 ,2 ¼ 7.6 Hz, H-100), 7.24–7.31 (m, 2H, 2
ꢁ00Ar-H), 7.38, 7.57 (2dd, 2H, 2 ꢁ Ar-H). 13C NMR (CDCl3):
d 24.8 (C-10), 30.6 (C-30), 47.5 (2 ꢁ CH2N), 47.6 (C-20), 67.0
(2 ꢁ CH2O), 113.5, 124.2, 125.6, 127.4, 123.0, 133.3 (C-Ar),
150.8, 152.2 (2 ꢁ C¼¼N). Anal. Calcd. for C15H17N3O2S
(303.00): C, 59.38, H, 5.65, N, 13.85, S, 10.57. Found: C,
59.70, H, 5.91, N, 13.50, S, 10.57.
0
00
0
ꢁ
C¼¼N), 169.3–170.5 (7
ꢁ
CO). Anal. Calcd. for
C38H47N3O18S (865.85): C, 52.71, H, 5.47, N, 4.85, S, 3.70.
Found: C, 52.45, H, 5.80, N, 4.75, S, 3.58.
2,3-Bis(ꢂ20,30-epoxypropyl-10-sulfanyl)quinoxaline (24). The
2-(5-Acetoxy-3-oxapent-1-yl-sulfanyl)-3-morpholin-1-yl-qui-
noxaline (29). The residue was purified by flash column chro-
matography using hexane–ethylacetate (H/E 6/1) to give 29 as
a syrup. 1H NMR (CDCl3): d 2.03 (s, 3H, CH3CO), 3.45 (t,
residue was purified by flash column chromatography using
hexane–ethylacetate (H/E 6/1) to give 24 as a syrup. H NMR
1
0
00
0
0
(CDCl3): d 3.71 (dd, 4H, J3 ,3 ¼ 6.1 Hz, J3 ,2 ¼ 2.3 Hz, 2 ꢁ
H-30, 2 ꢁ H-300), 4.28–4.29 (m, 4H, 2 ꢁ CH2S), 4.78 (bd, 2H,
2 ꢁ H-20), 7.60, 7.85 (4H, Ar-H). 13C NMR (CDCl3): d 35.3
(2 ꢁ CH2S), 47.4 (2 ꢁ C-30), 71.1 (2 ꢁ C-20), 127.6, 129.3,
2H, J1 ,1 ¼ 9.2 Hz, H-10, H-100), 3.70–3.74 (m, 4H, 2 ꢁ
0
00
0
00
CH2N), 3.80–3.92 (m, 4H, 2 ꢁ CH2O), 4.20 (dd, 2H, J5 ,5
¼
13.7 Hz, J5 ,4 ¼ 4.6 Hz, H-50, H-500), 4.74 and 5.66 (2d, 4H,
H-20, H-200, H-40, H-400), 7.50–7.57, 7.80–7.87 (2m, 4H, Ar-H).
13C NMR (CDCl3): d 21.0 (CH3), 38.7 (C-10), 49.9 (2 ꢁ
CH2N), 63.6 (C-50), 66.8 (2 ꢁ CH2O), 68.9 (C-40), 71.0 (C-20),
127.3, 127.4, 128.5, 128.9, 139.0 (C-Ar), 149.9, 153.6 (2 ꢁ
C¼¼N), 171.1 (C¼¼O). Anal. Calcd. for C18H23N3O4S (377.47):
C, 57.28; H, 6.14; N, 11.13; S, 8.49. Found C, 57.39; H, 6.45;
N, 11.27; S, 8.11.
0
0
139.2 (C-Ar), 154.6 (2
C14H14N2O2S2 (306.40): C, 54.88, H, 4.51, N, 9.14, S, 20.93.
Found: C, 54.50, H, 4.30, N, 9.20, S, 20.50.
ꢁ
CAS). Anal. Calcd. for
2,3-Bis[(ꢂ)-20,30-O-isopropylidene-20,30-dihydroxy-propyl-10-
sulfanyl]quinoxaline (25). The residue was purified by flash
column chromatography using hexane–ethylacetate (H/E 5/1)
to give 25. 1H NMR (CDCl3): d 1.36, 1.49 (2s, 12H, 4 ꢁ
CH3), 3.46–3.48 (m, 2H, 2 ꢁ H-20), 3.70 (dd, 2H, J3 ,2 ¼ 5.3
00
0
Hz, J3 ,3 ¼ 13.0 Hz, 2 ꢁ H-300), 3.84 (dd, 2H, J1 ,2 ¼ 6.1 Hz,
00
0
0
0
Acknowledgment. The continued support from AvH foundation
in Germany is highly appreciated.
J1 ,1 ¼ 8.4 Hz, 2 ꢁ H-10), 4.14 (dd, 2H, J1 ,2 ¼ 6.1 Hz, J1 ,1
0
00
00
0
00
0
¼ 8.4 Hz, 2 ꢁ H-100), 4.45–4.49 (m, 2 ꢁ H-30), 7.56, 7.87 (2
dd, 4H, Ar-H). 13C NMR (CDCl3): d 25.7, 27.1 (4 ꢁ CH3),
68.8 (2 ꢁ C-30), 74.5 (2 ꢁ C-20), 109.8 (CH3CCH3), 127.6,
128.4, 139.8 (C-Ar), 153.2 (2 ꢁ C¼¼N). Anal. Calcd. for
C20H26N2O4S2 (422.55): C, 56.79, H, 6.20, N, 6.63, S, 15.14.
Found: C, 56.51, H, 6.30, N, 6.89, S, 15.25.
REFERENCES AND NOTES
[1] (a) El Ashry, E. S. H.; Rashed, N.; Shobier, A. H. Pharma-
zie 2000, 55, 251; (b) El Ashry, E. S. H.; Rashed, N.; Shobier, A. H.
Pharmazie 2000, 55, 331; (c) El Ashry, E. S. H.; Rashed, N.; Shobier,
A. H. Pharmazie 2000, 55, 403.
2,3-Bis(allylsulfanyl)quinoxaline (26). Crystallized from
1
ethanol. H NMR (CDCl3): d 4.03 (d, 4H, J ¼ 6.8 Hz, 2 ꢁ H-
10, 2 ꢁ H-100), 5.17 (d, 2H, J ¼ 9.9 Hz, 2 ꢁ H-30), 5.40 (d,
2H, J ¼ 16.8 Hz, 2 ꢁ H-300), 5.98–6.05 (m, 2H, 2 ꢁ H-20),
7.55, 7.85 (2dd, 4H, Ar-H). 13C NMR (CDCl3): d 33.2 (2 ꢁ
C-10), 118.7 (2 ꢁ C-20), 127.5, 128.1 (C-Ar), 133.0 (2 ꢁ C-
30), 139.9, 153.7 (2 ꢁ C¼¼N). Anal. Calcd. for C14H14N2S2
(274.40): C, 61.28, H, 5.14, N, 10.21, S, 23.37. Found: C,
61.23, H, 5.00, N, 10.24, S, 23.10.
[2] (a) El Ashry, E. S. H.; Awad, L. F.; Atta, A. I. Tetrahedron
2006, 62, 2943; (b) El Ashry, E. S. H.; Rashed, N.; Ibrahim, S. I. Curr
Org Synth 2005, 2, 147; (c) El Ashry, E. S. H.; El Nemr, A. Synthesis
of Naturally Occurring Nitrogen Heterocycles from Carbohydrates;
Blackwell: Oxford, UK, 2005.
[3] (a) Demchenko, A. V.; Malysheva, N. N.; De Maeo, C. Org
Lett 2003, 5, 455; (b) Pornsuriyasak, P.; Demchenko, A. V. Chem Eur
J 2006, 12, 6630.
(ꢂ)-2-(20,30-O-Isopropylidene-20,30-dihydroxy-propyl-10-sul-
fanyl)-3-morpholin-1-yl-quinoxaline (27). Purified by flash
column chromatography using hexane–ethylacetate (H/E 6/1).
1H NMR (CDCl3): d 1.36, 1.49 (2s, 6H, 2 ꢁ CH3), 3.43–3.47
[4] (a) Robina, I.; Vogel, P.; Witczak, Z. J Curr Org Chem
2001, 5, 1177; (b) Horton, D.; Huston, D. H. Adv Carbohydr Chem
1963, 18, 123; (c) Witczak, Z. J Curr Med Chem 1999, 6, 165.
[5] (a) Sana, P.; Carta, A.; Loriga, M.; Zanetti, S.; Sechi, L. II
Farmaco 1999, 54, 161; (b) Ali, M. M.; Ismail, M. M. F.; El-Gaby, M.
S. A.; Zahran, M. A.; Ammar, Y. A. Molecules 2000, 5, 864; (c) Law-
rence, D. S.; Copper, J. E.; Smith, C. D. J Med Chem 2001, 44, 594;
(d) Ries, U. J.; Priepke, H. W. M.; Hauel, N. H.; Handschuh, S.;
Mihm, G.; Stassen, J. M.; Wienen, W.; Nar, H. Bioorg Med Chem
Lett 2003, 13, 2297.
(m, 5H, 2 ꢁ CH2N, H-100), 3.57 (dd, 1H, J3 ,2 ¼ 6.1 Hz, J3 ,3
0
0
0
00
¼ 8.4 Hz, H-30), 3.82 (dd, 1H, J1 ,1 ¼ 8.4 Hz, J1 ,2 ¼ 6.1 Hz,
0
00
0
0
H-10), 3.90 (t, 4H, 2 ꢁ CH2O), 4.12 (dd, 1H, J3 ,2 ¼ 6.1 Hz,
00
0
J3 ,3 ¼ 8.4 Hz, H-300), 4.45–4.50 (m, 1H, H-20), 7.40–7.47 (m,
2H, 2 ꢁ Ar-H), 7.80–7.90 (m, 2H, 2 ꢁ Ar-H). 13C NMR
(CDCl3): d 25.7, 27.1 (2 ꢁ CH3), 32.8 (C-10), 49.8 (2 ꢁ
00
0
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

56
R. Beldi, K. F. Atta, S. Aboul-Ela, and E. S. H. El Ashry
Vol 48
[6] (a) Lidstrom, P.; Wathey, B.; Westman, J. Tetrahedron
Abbasi, M. M. A.; Ibrahim, E. I.; Soliman, A. H.; El Ashry, E. S. H.
Heterocycl Commun 1999, 5, 577.
2001, 57, 9225; (b) Perreux, L.; Loupy, A. Tetrahedron 2001, 57, 9199.
[7] (a) El Ashry, E. S. H.; Ramadan, E.; Kassem, A. A.; Hagar,
M. Adv Heterocycl Chem 2005, 88, 1; (b) El Ashry, E. S. H.; Kassem,
A. A.; Ramadan, E. Adv Heterocycl Chem 2005, 90, 1; (c) El Ashry,
E. S. H.; Kassem, A. A. Arkivoc 2006, 1.
[10] El Ashry, E. S. H.; Fahmy, K.; Abu-Elela, S.; Beldi, R. J
Carbohydr Chem 2007, 26, 1.
[11] El Ashry, E. S. H.; Awad, L. A.; Abdel Hamid, H. M.;
Atta, A. I. Synth Commun 2006, 36, 2769.
[8] (a) El Ashry, E. S. H.; Rashed, N.; Awad, L. F.; Ramadan,
E. S.; Abdel-Maggeed, S. M.; Rezki, N. J Carbohydr Chem 2008, 27,
70; (b) El Ashry, E. S. H. In Heterocycles from Carbohydrate Precur-
sors, Topics in Heterocyclic Chemistry; Gupta; Springer, 2007; p 7.
[9] (a) Abdel Hamid, H. M.; Moussad, A.; Ramadan, E.; El
Ashry, E. S. H. Heterocycl Commun 1999, 5, 473; (b) Khodair, A. I.;
[12] Morrison, D. C.; Furst, A. J Org Chem 1956, 21, 470.
[13] Wagner, G.; Frenzel, H. Arch Pharm 1967, 433.
[14] William, A. B.; James, E. K. J Am Chem Soc 1951, 73,
2241.
[15] El Ashry, E. S. H.; Awad, L. F.; Abdel Hamid, H. M.;
Atta, A. I. J Carbohydr Chem 2005, 24, 745.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet