Microwave-assisted organic synthesis of 3-(D-Gluco-pentitol-1-YL)-1H-1,2,4- triazole

Article abstract of DOI:10.1080/15257770500544545

The condensation of D-glucono- and D-galactono-1,5-lactone and thiocarbohydrazide to give 3-(D-alditol-1-yl)-4-amino-5-mercapto-1,2,4-triazoles 4 and 5 is accelerated by the use of microwave-assisted organic reaction (MAOS). The deamination and dethiolati

Full text of DOI:10.1080/15257770500544545

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Microwave-Assisted Organic Synthesis
of 3-(D-gluco- Pentitol-1-Yl)-1H-1,2,4-
Triazole
E. S. H. El Ashry a , L. F. Awad a , H. M. Abdel Hamid a & A. I. Atta b
a Chemistry Department, Faculty of Science, Alexandria University,
Alexandria, Egypt
b Faculty of Medical Sciences, Al-Hodiedah University, Hodiedah,
Yemen
Version of record first published: 23 Aug 2006.
To cite this article: E. S. H. El Ashry , L. F. Awad , H. M. Abdel Hamid & A. I. Atta (2006): Microwave-
Assisted Organic Synthesis of 3-(D-gluco- Pentitol-1-Yl)-1H-1,2,4-Triazole, Nucleosides, Nucleotides
and Nucleic Acids, 25:3, 325-335
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Nucleosides, Nucleotides, and Nucleic Acids, 25:325–335, 2006
Copyright ꢀ Taylor & Francis Group, LLC
C
ISSN: 1525-7770 print / 1532-2335 online
DOI: 10.1080/15257770500544545
MICROWAVE-ASSISTED ORGANIC SYNTHESIS
OF 3-(D-GLUCO-PENTITOL-1-YL)-1H-1,2,4-TRIAZOLE
E. S. H. El Ashry, L. F. Awad, and H. M. Abdel Hamid
Chemistry Department,
2
Faculty of Science, Alexandria University, Alexandria, Egypt
A. I. Atta
Faculty of Medical Sciences, Al-Hodiedah University, Hodiedah, Yemen
2
The condensation of D-glucono- and D-galactono-1,5-lactone and thiocarbohydrazide to give
2
3-(D-alditol-1-yl)-4-amino-5-mercapto-1,2,4-triazoles 4 and 5 is accelerated by the use of microwave-
assisted organic reaction (MAOS). The deamination and dethiolation of compound 4 to give 6 was
also accelerated by the use of MAOS. Condensation of 4 and 5 with p-nitrobenzaldehyde afforded
Schiff bases 8 and 9, respectively, within 4 min under microwave irradiation (MWI), whereas with
ethyl chloroacetate the thioalkylated products 14 and 15 were obtained in 8 min. The structures of
the synthesized compounds were confirmed by 1H NMR, 2D NMR, and mass spectra.
Keywords MAOS; MWI; 1,2,4-Triazoles; Acyclonucleosides; Seco C-Nucleosides
INTRODUCTION
Microwave-assisted organic synthesis (MAOS) has experienced exponen-
tial growth in the last several years. The use of MAOS often provides higher
yields and purities when compared to traditional synthetic method.[1] A part
of our ongoing program has been devoted to the use of microwave irra-
diation (MWI) to achieve and/or accelerate organic reactions.[2−9] 1,2,4-
Triazoles have gained an important place in medicinal chemistry as a result
of their pharmacological activities,[10−15] especially those having 4-amino-5-
mercapto-3–substituted derivatives.[16−18] Moreover, the syntheses of their
respective nucleosides and acyclonucleoside analogues have been under-
taken to enhance their biological activities.[19−25] We report herein the de-
tails for our preliminary results[26] for the synthesis of seco C-nucleosides of
1,2,4-triazole under the influence of microwave irradiation (MWI).
Recieved 11 July 2005; accepted 23 November 2005.
Prelimenary results were presented at: Int. Soc. for Nucleosides, Nucleotides & Nucleic Acids XVI
Int. Round Table, Minneapolis, Minnesota, USA, 2004, P5.
Address correspondence to E. El Ashry, Chemistry Department, Faculty of Science, Alexandria
University, Alexandria, Egypt. E-mail: eelashry60@hotmail.com; eelashry60@link.net
325

326
E. S. H. El Ashry et al.
EXPERIMENTAL
General Methods
Melting points were determined on a Mel-temp apparatus and are uncor-
rected. 1H NMR spectra were recorded on a Jeol spectrometer (500 MHz).
The chemical shifts are expressed on the δ-scale using Me4Si as a standard,
and coupling–constant values are given in Hz. The assignments of 1H NMR
spectra were based on chemical-shift correlation DQFCOSY spectra. TLC was
preformed on Merck silica gel 60F254 with detection by charring in sulfuric
acid and by UV light. Irradiation was achieved using a domestic microwave
oven EM-230 M (800 Watt output power). Microanalyses were preformed in
the Microanalysis Unit at the Faculty of Science, Cairo University.
3-(D-Alditol-1-yl)-4-amino-5-mercapto-1,2,4-triazoles (4, 5). General pro-
cedure. A mixture of 1 or 2 (0.028 mole, 4.98 g) and thiocarbohydazide
3 (0.028 mol, 2.63 g) in dry pyridine (2 mL) was placed in a Teflon screw-
capped vessel and was irradiated for 5–6 min in a microwave oven, then it
was left to cool. The product was washed with alcohol and crystallized.
4-Amino-3-(D-gluco-pentitol-1-yl)-5-mercapto-1,2,4-triazole (4). The pro-
duct was crystallized from methanol-water in white needles (88% yield); mp
201–203◦C; lit[18] mp 201–202 ◦C.
4-Amino-3-(D-galacto-pentitol-1-yl)-5-mercapto-1,2,4-triazole (5).
The
product was crystallized from methanol-water in white needles (80% yield);
mp 215–217◦C; lit[18] mp 214–215◦C.
3-(1,2,3,4,5-Penta-O-acetyl-D-gluco-pentitol-1-yl)-1H-1,2,4-triazole (7).
A
suspension of 4 (1.35 g, 5 mmol) in orthophosphoric acid (10 mL) was
treated with sodium nitrite (5N, 35 mL) at 0◦C. The reaction mixture was
irradiated in a microwave oven for 2 min, neutralized with 10% sodium
hydroxide, and then evaporated. The crude product was boiled with ethanol
and filtered, and the filtrate was evaporated to dryness. The resulting syrup
was dissolved in pyridine (15 mL), cooled to 0◦C, and then treated with
acetic anhydride (25 mL) and kept for overnight at room temperature. The
reaction mixture was poured into ice water and extracted with methylene
chloride. The organic layer was washed with water, dried over sodium
sulfate, and evaporated to give a syrup, which crystallized from ethanol to
give 17 as colorless crystals, 63% yield; mp 177–179◦C; lit[21] mp 177–178◦C.
3-(D-Gluco-pentitol-1-yl)-1H-1,2,4-triazole (6).
To a stirred solution of
7 (0.429 g, 1 mmol) in methanol (30 mL), ammonium hydroxide (20%,
7 ml) was added. The reaction mixture was allowed to stand overnight at

MAOS of 3-(D-Gluco-pentitol-1-yl)-1 H-1,2,4-Triazole
327
room temperature, then evaporated under reduced pressure. The crude
product was recrystallized from methanol-ether (70%, yield), mp 158–160◦C;
1H NMR (DMSO-d6 + D2O) δ: 3.20 (dd, 1 H, J5 ,4 = 3.8 Hz, J5 ,5 = 10.7 Hz,
ꢁꢁ
ꢁ
ꢁꢁ
ꢁ
H-5ꢁꢁ), 3.29 (dd, 1 H, J5 ,4 = 4.5 Hz, J5 ,5 = 10.7 Hz, H-5ꢁ), 3.42–3.45 (m, 1
ꢁ
ꢁ
ꢁ
ꢁꢁ
H, H-4ꢁ), 3.51 (dd, 1 H, J3 ,2 = 3.05 Hz, J3 ,4 = 10.7 Hz, H-3ꢁ), 3.92 (d, 1 H,
ꢁ
ꢁ
ꢁ
ꢁ
J2 ,1 = 6.8 Hz, H-2ꢁ), 4.76 (d, 1 H, J1 ,2 = 6.8 Hz, H-1ꢁ), 8.02 (s, 1 H, H-5
ꢁ
ꢁ
ꢁ
ꢁ
arom), 13.33 (s, 1 H, D2O exchangeable, NH).
3-(D-Alditol-1-yl)-4-(p-nitrobenzylidene)amino-5-mercapto-1H-1,2,4-triaz-
oles (8, 9).
Method (a). A mixture of the triazole 4 or 5 (0.27 g, 1 mmol),
p-nitrobenzaldehyde (0.15 g, 1 mmol), in DMF (10 mL) and p-toluen-
esulfonic acid (0.08 g) was heated at reflux for 8 h, cooled to room tempera-
ture, and poured into ice water. The product was filtered off and recrystallized
from ethanol.
Method (b). A mixture of the triazole 4 or 5 (0.27 g, 1 mmol),
p-nitrobenzaldehyde (0.15 g, 1 mmol), and p-toluenesulfonic acid (0.08 g) in
dry DMF (5 mL) was placed in an Erlenmeyer flask (100 mL) and irradiated
for 4 min. The reaction mixture was cooled to room temperature.
3-(D-Gluco-pentitol-1-yl)-4-(p-nitrobenzylidene)amino-5-mercapto-1H -1,
2,4-triazole (8).
The product was crystallized from ethanol to give yellow
crystals (61% from method a and 82% from method b); mp 220–222◦C; 1H
NMR (DMSO-d6 + D2O) δ: 3.13 (dd, 1 H, J5 ,4 = 8.4, J5 ,5 = 11.3 Hz, H-5ꢁꢁ),
ꢁꢁ
ꢁ
ꢁꢁ
ꢁ
3.31 (dd, 1 H, J5 ,4 = 5.3 Hz, J5 ,5 = 11.3 Hz, H-5ꢁ), 3.58–3.48 (m, under
ꢁ
ꢁ
ꢁ
ꢁꢁ
solvent, 2 H, H-3ꢁ, H-4ꢁ), 4.20 (d, 1 H, J2 ,1 = 8.5 Hz, H-2ꢁ), 4.84 (d, 1 H, J1 ,2
ꢁ
ꢁ
ꢁ
ꢁ
= 8.5 Hz, H-1ꢁ), 8.15 (d, 2 H, J = 7.6 Hz, H-2, H-6), 8.33 (d, 2 H, J = 8.4 Hz,
H-3, H-5), 10.15 (s, 1 H, CH N), 14.00 (s, 1 H, D2O exchangeable, SH).
3-(D-Galacto -pentitol-1-yl)-4-(p-nitrobenzylidene)amino-5-mercapto-1H-
1,2,4-triazole (9).
The product was crystallized from ethanol to give yellow
crystals (63% from method a and 80% from method b); mp 255–257◦C;
1H NMR (DMSO-d6 + D2O) δ: 3.32–3.39 (m, 2 H, H-5ꢁ, H-5ꢁꢁ), 3.53 (dd,
1 H, J3 ,2 = 9.2 Hz, H-3ꢁ), 3.71 (m under solvent, 1 H, H-4ꢁ), 3.89 (dd, 1 H,
ꢁ
ꢁ
J2 ,1 = 2.3 Hz, J2 ,3 = 9.2 Hz, H-2ꢁ), 5.06 (d, 1 H, J1 ,2 = 2.3 Hz, H-1ꢁ), 8.15
(d, 2 H, J = 7.7 Hz, H-2, H-6), 8.32 (d, 2 H, J = 8.4 Hz, H-3, H-5), 10.37 (s,
1 H, CH N), 13.90 (s, 1 H, D2O exchangeable, SH).
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
3-(1,2,3,4,5-Penta-O-acetyl-D-alditol-1-yl)-4-(p-nitrobenzylidene)amino-5-
mercapto-1H-1,2,4-triazole (11, 12).
A cold solution of 8 or 9 (0.133 g,
0.33 mmol) in dry pyridine (1 ml) was treated with acetic anhydride
(1.5 mL), the reaction mixture was kept overnight at room temperature,
and poured into ice-cold water.

328
E. S. H. El Ashry et al.
3-(1,2,3,4,5-Penta-O-acetyl-D-gluco-pentitol-1-yl)-4-(p-nitrobenzylidene)-
amino-5-mercapto-1H-1,2,4-triazole (11).
The crude product was recystal-
1
lized from ethanol to give yellow crystals (85% yield), mp 187–189◦C; H
NMR (CDCl3) δ: 2.01, 2.02, 2.06, 2.07, 2.08 (5s, 15 H, 5 × OAc), 4.12 (dd,
1 H, J5 ,4 = 5.3 Hz, J5 ,5 = 12.3 Hz, H-5ꢁꢁ), 4.22 (dd, 1 H, J5 ,4 = 3.05 Hz,
ꢁꢁ
ꢁ
ꢁꢁ
ꢁ
ꢁ
ꢁ
J5 ,5 = 12.3 Hz, H-5ꢁ), 5.16 (ddd, 1 H, J4 ,5 = 5.3 Hz, J4 ,5 = 3.05 Hz, J4 ,3
ꢁ
ꢁꢁ
ꢁ
ꢁꢁ
ꢁ
ꢁ
ꢁ
ꢁ
= 8.4 Hz, H-4ꢁ), 5.39 (dd, 1 H, J3 ,4 = 8.4 Hz, J3 ,2 = 2.3 Hz, H-3ꢁ), 6.0 (dd,
ꢁ
ꢁ
ꢁ
ꢁ
1 H, J2 ,3 = 2.3 Hz, J2 ,1 = 8.4 Hz, H-2ꢁ), 6.3 (d, 1 H, J1 ,2 = 8.4 Hz, H-1ꢁ),
8.08 (d, 2 H, J = 9.2 Hz, H-2, H-6), 8.41 (d, 2 H, J = 8.4 Hz, H-3, H-5), 10.93
(s, 1 H, CH N), 11.05 (s, 1 H, D2O exchangeable, SH).
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
3-(1,2,3,4,5-Penta-O-acetyl-D-galacto-pentitol-1-yl)-4-(p-nitrobenzylidene)-
amino-5-mercapto-1H-1,2,4-triazole (12).
The crude product was recystal-
1
lized from ethanol to give yellow crystals (83% yield), mp 183–185◦C; H
NMR (CDCl3) δ: 2.01, 2.03, 2.17, 2.18, 2.21 (5s, 15 H, 5 × OAc), 3.93 (dd, 1
H, J5 ,4 = 7.6 Hz, J5 ,5 = 11.5 Hz, H-5ꢁꢁ), 4.32 (dd, 1 H, J5 ,4 = 4.3 Hz, J5 ,5
ꢁꢁ
ꢁ
ꢁꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁꢁ
= 11.5 Hz, H-5ꢁ), 5.41 (m, 1 H, H-4ꢁ), 5.58 (m, 2 H, H-3ꢁ, H-2ꢁ), 6.14 (d, 1
H,J1 ,2 = 1.9 Hz, H-1ꢁ), 8.07 (d, 2 H, J = 8.6 Hz, H-2, H-6), 8.38 (d, 2 H,J =
8.6 Hz, H-3, H-5), 10.21 (s, 1 H, CH N), 11.01 (s, 1 H, D2O exchangeable,
SH).
ꢁ
ꢁ
4-Amino-3-(1,2,3,4,5-penta-O-acetyl-D-alditol-1-yl)-5-(ethoxycarbonylmet-
hyl)thio-1,2,4-triazoles (18, 19).
Method (a). A mixture of 4 or 5 (0.27 g, 1 mmol), ethyl chloroacetate
(0.122 g, 1mmol), and sodium acetate (0.016 g, 0.2 mmol) in absolute
ethanol (25 mL) was refluxed for 18 h. The solvent was evaporated under
reduced pressure to dryness. The resulting syrup was dissolved in pyridine
(3 mL), cooled to 0◦C, and then treated with acetic anhydride (5 mL). The
reaction mixture was kept overnight at room temperature, poured into ice
water, and extracted with chloroform. The organic layer was washed with
water, dried over anhydrous sodium sulfate, and evaporated to give a syrup,
which was purified by column chromatography.
Method (b). A mixture of 4 or 5 (0.27 g, 1 mmol), ethyl chloroac-
etate (0.122 g, 1 mmol), and sodium acetate (0.016 g, 0.2 mmol) in ab-
solute ethanol (5 mL) was placed in a Teflon screw-capped vessel and
microwave-irradiated for 8 min. Then the reaction mixture was process as in
method a.
4-Amino-3-(1,2,3,4,5-penta-O-acetyl-D-gluco-pentitol-1-yl)-5-(ethoxycarbo-
nylmethyl)thio-1,2,4-triazole (18).
The crude product was eluted with
(petroleum ether/ethyl acetate, 1:4) to give 18 as a syrup (51% method
1
a and 61% method b), H NMR (CDCl3) δ: 1.28 (t, 3 H, J = 7.6 Hz,
CH3), 1.96, 2.01, 2.10, 2.11, 2.13 (5s, 15 H, 5 × OAc), 3.89, 3.97 (2d, 2 H,

MAOS of 3-(D-Gluco-pentitol-1-yl)-1 H-1,2,4-Triazole
329
Jgem = 16.8 Hz, SCH2), 4.08 (dd, 1 H, J5 ,4 = 7.6 Hz, J5 ,5 = 12.3 Hz, H-5ꢁꢁ),
ꢁꢁ
ꢁ
ꢁꢁ
ꢁ
4.15 (dd, 1 H, J5 ,4 = 3.1 Hz, J5 ,5 = 12.3 Hz, H-5ꢁ), 4.23 (q, 2 H, OCH2),
ꢁ
ꢁ
ꢁ
ꢁꢁ
4.98 (dd, 1 H, J3 ,4 = 9.2 Hz, J3 ,2 = 1.5 Hz, H-3ꢁ), 5.03 (m, 1 H, H-4ꢁ), 5.32
ꢁ
ꢁ
ꢁ
ꢁ
(s, 2 H, D2O exchangeable, NH2), 5.69 (d, 1 H, J1 ,2 = 9.2 Hz, H-1ꢁ), 6.18
ꢁ
ꢁ
(dd, 1 H, J2 ,3 = 1.5 Hz, J2 ,1 = 9.2 Hz, H-2ꢁ).
ꢁ
ꢁ
ꢁ
ꢁ
4-Amino-3-(1,2,3,4,5-penta-O-acetyl-D-galacto-pentitol-1-yl)-5-(ethoxy
carbonylmethyl)thio-1,2,4-triazole (19).
The crude product was eluted
with (petroleum ether/ethyl acetate, 1:4) to give 19 as a syrup (53% method
1
a and 63% method b), H NMR (500 MHz, CDCl3) δ: 1.25 (t, 3 H, J =
7.6 Hz, CH3), 1.94, 2.01, 2.03, 2.07, 2.11 (5s, 15 H, 5 × OAc), 3.78, 3.84
ꢁꢁ
ꢁ
ꢁꢁ
ꢁ
(2d, 2 H, Jgem = 17.6 Hz, SCH2), 3.92 (dd, 1 H, J5 ,4 = 7.65 Hz, J5 ,5
=
=
ꢁ
11.5 Hz, H-5ꢁꢁ), 4.18 (q, 2 H, OCH2), 4.28 (dd, 1 H,J5 ,4 = 6.1 Hz, J5 ,5
ꢁ
ꢁ
ꢁ
ꢁꢁ
11.5 Hz, H-5ꢁ), 5.25 (s, 2 H, D2O exchangeable, NH2), 5.38 (dd, 1 H, J4 ,5
ꢁ
= 6.1 Hz,J4 ,3 = 6.9 Hz, H-4ꢁ), 5.55-5.59 (m, 2 H, H-2’, H-3ꢁ), 6.07 (d, 1 H,
ꢁ
ꢁ
J1 ,2 = 2.3 Hz, H-1ꢁ).
ꢁ
ꢁ
RESULTS AND DISCUSSION
D-Glucono- and D-galactono-1,5-lactones (1, 2) and thiocarbohydrazide
(3) were chosen as building blocks for constructing certain seco C-
nucleosides; for example, using these building blocks, we obtained 4-amino-
3-(D-gluco- and D-galacto-pentitol-1-yl)-5-mercapto-1,2,4-triazoles (4 and 5)
in 88 and 80% yield, respectively, under microwave irradiation (MWI)
within a shorter reaction times (5–6 min) compared to conventional heat-
ing (Scheme 1).[18] Recently, we published a new method for a one-
pot deamination and dethiolation of 4-amino-3-(D-gluco-pentitol-1-yl)-5-
mercapto-1,2,4-triazole 4 using sodium nitrite in orthophosphoric acid.[21]
Attempted acceleration of the reaction with MWI for 2 min gave similar
results.
SCHEME 1
The reaction mixture was neutralized with sodium hydroxide and acety-
lated to give 7 in an improved yield (63%) compared to that obtained by con-
ventional heating (52%).[21] Deacetylation of 7 with ammonium hydroxide

330
E. S. H. El Ashry et al.
SCHEME 2
in methanol afforded the respective acyclo C-nucleoside 6 (Scheme 2). The
1H NMR spectrum of 6 showed in addition to the sugar five hydroxyl ex-
changeable protons, an exchangeable singlet in the low field region at δ
13.33 due to the NH proton. H-5 of the triazole moiety was assigned to a
singlet at δ 8.02. At higher field, the sugar protons H-1ꢁ and H-2ꢁ resonated at
δ 4.76 and 3.92, respectively, whereas H-3ꢁ, H-5ꢁ and H-5ꢁꢁ each resonated as a
doublet of doublets at δ 3.51, 3.29, and 3.20, respectively. The H-4ꢁ multiplet
resonated at δ3.42–3.45.
A possible mechanism for the deamination and dethiolation process
could be due to the formation of the N-nitroso intermediate, which under-
goes a [3.3] sigmatropic rearrangement followed by the loss of a molecule of
nitrogen to form intermediate I, which tautomerize to II and loses a molecule
of sulfur monoxide under the basic conditions. Subsequent acetylation of tri-
azole 6 gave the respective seco C-nucleoside 7 (Scheme 3).
SCHEME 3

MAOS of 3-(D-Gluco-pentitol-1-yl)-1 H-1,2,4-Triazole
331
SCHEME 4
The 4-amino-5-mercapto-1,2,4-triazole ring system is a versatile key in-
termediate for the synthesis of N- and S-bridged heterocyclic derivatives. We
were interested in studying the effect of MWI on the 4-amino-mercapto-1,2,4-
triazole system found in compounds 4 and 5 (Scheme 4). Condensation of
a mixture of 4 or 5 with p-NO2benzaldehyde in DMF in the presence of a
catalytic amount of PTSA provided 8 and 9 in moderate yields (61–63%)
under conventional heating conditions, whereas the yields were improved
to 80–82% using MWI. Surprisingly, no 1,2,4-triazolo[3,4-b]1,3,4-thiadiazole
(10) was formed during either of the reaction conditions. The uncyclized
nature of 8 and 9 was confirmed from the study of their 1H NMR spectra as
well as those of their acetylated derivatives 11 and 12, which were obtained
by conventional acetylation of 8 and 9 with acetic anhydride in pyridine.
The existence of a characteristic exchangeable singlet for the SH proton at
the downfield region at δ 13.90–14.00 and 11.01–11.05 for 8, 9 and 11, 12,
respectively, ruled out their existence either in the thione structure 13 or

332
E. S. H. El Ashry et al.
the cyclized form 1,2,4-triazolo[3,4-b]1,3,4-thiadiazole structure 10. More-
over, the assigned azomethine proton at δ 10.15–10.37 and 10.21–10.93 for
8, 9 and 11, 12, respectively, was also in agreement with the assigned acyclic
structures 8 and 9 rather than the cyclized one 10.
Three possible structures could be expected from the carboxymethyla-
tion of 4 and 5 with ethyl chloroacetate in the presence of sodium acetate
under microwave irradiation. One of these expected products is a S-alkyl
derivatives such as 14 and 15. Compounds 14 and 15 could provide two
additional products 16 and 17 after ring closure with loss of ethanol or wa-
ter, respectively. Acetylation of 14 and 15 with acetic anhydride in pyridine
gave 4-amino-3-(1,2,3,4,5-penta-O-acetyl-D-gluco and D-galacto-pentitol-1-yl)-5-
(ethoxycarbonylmethy)thio-1,2,4-triazoles 18 and 19. Spectral data ruled out
the formation of the cyclized products 16 and 17 (Scheme 5).
SCHEME 5
Moreover, verification of the uncyclized structure was confirmed from
the mass spectrum of 18, which showed a molecular ion peak at m/z 562 in
agreement with the molecular formula C21H30N4O12S. A C-1-C-2 bond fission
of the alditolyl moiety followed by loss of ketene afforded a base peak at m/z
231 (100%), which reflects the stability of the 1,2,4-triazole ring towards

MAOS of 3-(D-Gluco-pentitol-1-yl)-1 H-1,2,4-Triazole
333
electron bombardment.[17,19] A loss of EtO2C and NH2 radicals from the
base peak afforded a fragment at m/z 142 (Scheme 6).
SCHEME 6
In addition to the other expected sugar protons in the 1H NMR spectra
of 18 and 19, two exchangeable protons corresponding to the NH2 protons
resonated at δ 5.32 and 5.25, respectively. Two doublets of the AB type spin
system with Jgem 16.8 and 17.6 Hz, respectively, were attributed to the SCH2
protons, which indicated that these two protons are not equivalent.[21] The
1H-1H DQFCOSY technique facilitated the correlation of protons with each
other. Thus, the higher frequency region H-2ꢁ of compound 18 was assigned
as doublet of doublets at δ 6.18 and coupled with H-1ꢁ (d, δ 5.69) and H-3ꢁ
(dd, δ 4.98), which in turn was correlated with H-4ꢁ (m, δ 5.03–5.05). H-5ꢁ
was assigned to a doublet of doublets at δ 4.15 coupled with H-5ꢁꢁ and H-4ꢁ.
The signals corresponding to the ethyl moiety were assigned to a triplet at
δ 1.28 corresponding to CH3 group and correlated with the quartet signal
due to CH2 at δ 4.23.
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