Synthesis and reactions of 1,5- and 1,3-dialkyl-(D-manno-pentitol-1-yl)-1H-1,2,4-triazole nucleosides derived from 1-(chloroalkyl)-1-aza-2-azoniaallene salts

Article abstract of DOI:10.1016/S0008-6215(99)00084-1

1-(Chloroalkyl)1-aza-2-azoniaallene salts underwent cycloaddition with penta-O-benzoyl-D-mannonic acid nitrile to give several intermediates. The salts of these rearranged spontaneously to the protonated 1,2,4-triazoles, which hydrolysed, in situ, to the

Full text of DOI:10.1016/S0008-6215(99)00084-1

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Carbohydrate Research 318 (1999) 67–74
Synthesis and reactions of 1,5- and
1,3-dialkyl-(
D
-manno-pentitol-1-yl)-1H-1,2,4-triazole
nucleosides derived from
1-(chloroalkyl)-1-aza-2-azoniaallene salts
Najim A. Al-Masoudi a,*, Yaseen A. Al-Soud b, Irene M. Lagoja a
a Fakulta¨t fu¨r Chemie, Uni6ersita¨t Konstanz, Postfach 5560, D-78434 Konstanz, Germany
b Department of Chemistry, College of Science, Uni6ersity of Al al-Bayt, Al-Mafraq, Jordan
Received 4 January 1999; accepted 29 March 1999
Abstract
1-(Chloroalkyl)1-aza-2-azoniaallene salts underwent cycloaddition with penta-O-benzoyl-
D
-mannonic acid nitrile
to give several intermediates. The salts of these rearranged spontaneously to the protonated 1,2,4-triazoles, which
hydrolysed, in situ, to the acyclic 1,2,4-triazole C-nucleosides. Deblocking of the latter afforded the free nucleosides.
Analogous treatment of 1,1-tert-butylmethyl derivatives of 1-aza-2-azoniaaallene salts with penta-O-benzoyl-
nonic acid nitrile gave, after rearrangment and hydrolysis, acyclic C-nucleosides which on deblocking furnished the
free nucleosides. Acetalation of 1-ethyl-3-( -manno-pentitol-1-yl)-5-methyl-1H-1,2,4-triazole and 5-( -manno-penti-
D-man-
D
D
tol-1-yl)-3-methyl-1-(1,2,4-trichlorophenyl)-1H-1,2,4-triazole with acetone and dimethoxypropane in the presence of
acid afforded their 2,3:4,5-diacetal derivatives © 1999 Elsevier Science Ltd. All rights reserved.
Keywords: Acetalation; Acyclic C-nucleosides; Cycloadditions; Cumulenes; Sugar nitrile
against herpes simplex viruses (HSV 1 and 2)
1. Introduction
prompted us to study synthetic approaches
[16,17] to prepare new 1,2,4-triazole C-nu-
cleoside analogues as promising potentially
biological active candidates. Some of these
nucleosides have been selected recently for
biological study as potential herbisides, fun-
gisides or insectisides [18]. A recent review on
C-nucleosides contained more than 1000 refer-
ences [19].
In the 1970s, a considerable number of C-
glycosyl nucleosides were isolated from natu-
ral products [1,2], but only a few 1,2,4-triazole
C-ribofuranosides were documented [3–8].
These compounds were prepared as analogues
[9] of the potent antiviral N-nucleoside rib-
avirin [10–14] because of their broad spec-
trum of action against RNA and DNA
viruses. The antiviral properties of some
acyclic 1,2,4-triazole C-nucleosides [15]
We describe here the synthesis of some
acyclic
nucleosides
(chloroalkyl)-1-aza-2-azoniaallene salts (3)
D
-manno-pentitol of 1,2,4-triazole C-
via cycloaddition of 1-
* Corresponding author: Fax: +49-7531-883-138.
E-mail address: masoudi@chclu.chemie.uni-konstanz.de
(N.A. Al-Masoudi)
[20–24] with the penta-O-benzoyl-
D
-man-
nonic acid nitrile (5) [25].
0008-6215/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(99)00084-1

68
N.A. Al-Masoudi et al. / Carbohydrate Research 318 (1999) 67–74
manno-pentitol-1-yl)-3H-1,2,4-triazolium hex-
2. Results and discussion
achloroantimonates 6. When the temperature
was raised above −30 °C, 6 furnished the
protonated triazoles 7 by [1,2] migration
[26,27] of the alkyl group (R2) from C-3 to
N-2 and elimination of the (CClR1R2) group
from N-1. The C-nucleosides 8a–d were ob-
tained from hydrolysis of the triazolium salts
7a–d, in situ, with aqueous NaHCO3 [26,28]
in good yields. Treatment of 8a–d with
NaOMe in MeOH afforded the free nu-
cleosides 9a–d in 81–90% yields (Scheme 1).
The heterocumulenes 11 with tert-butyl
group were used to synthesize electrically neu-
tral 2-unsubstituted 1,2,4-triazoles [26,28].
Thus, 1-aza-2-azoniaallene salts 11, formed at
low temperature from the 1-chloroalkyl azo
compounds 10 [16–18,20–30] on treatment
with a Lewis acid such as SbCl5, was reacted
with the nitrile 5 to give the inseparable salts
12. The formation of the intermediate 13,
resulting from elimination of the bulky tert-
butyl group and [1,2] H-shift, proves that
sterically electron-withdrawing substituents
In our recent work [16–18], various 1,2,4-
triazole C-nucleosides were synthesized from
cycloaddition of the short-lived reactive inter-
mediates 1-(chloroalky)-1-aza-2-azoniaallenes
(3) and 1-aza-2-azoniaallenes (4) (R1, R2=
alkyl, R3 =CO2Et or aryl) with the glycosyl
and the acyclic (2-hydroxyethoxy)alkyl
cyanides. In the present study, the reactive
intermediates 3 and 1,2,3,4,5-penta-O-ben-
zoyl- -mannonic acid nitrile (5) have been
D
selected for the synthesis of some new 1,2,4-
triazole C-nucleosides. The sugar nitrile 5 was
prepared from hydroxylamination of
D-man-
nose followed by benzoylation at 50 °C, then
at room temperature for 24 h. Chlorination of
the hydrazones 1 afforded the dichlorides 2,
which were converted, at approximately −
60 °C, to the salts 3 in the presence of SbCl5.
At approximately −30 °C the color changed
from orange to brown, indicating that 3
underwent cycloaddition reaction with
sugar nitrile 5 to give the unseparable 5-( -
D
Scheme 1.

N.A. Al-Masoudi et al. / Carbohydrate Research 318 (1999) 67–74
69
Scheme 2.
6.70. The doublet of doublets of doublets
appeared in the region l 5.78–5.90 with J
couplings between 3.2 and 3.7 Hz being at-
tributed to H-4%. The doublet of doublets at l
4.86, 4.82, 4.84, 4.90, 4.85 and 4.82 with J
couplings 5.8, 5.4, 5.5, 6.3, 5.2, 5.3 and 5.3 Hz,
respectively, were assigned to H-5%. The H-5
appeared as a doublet of doublets in the re-
gion l 4.49–4.63 with geminal coupling ꢀ
12.0 Hz. The alkyl groups at N-1 and C-5
were assigned. The free nucleosides 8a–d and
15a–c were characterized by two-dimensional
NMR spectroscopy. The procedures are al-
ready described [17,31].
forming stable carbonium ions can escape
during the [1,2] shift [28]. Hydrolysis of 13, in
situ, with aqueous NaHCO3 gave the nu-
cleosides 14a–c in good yields. Successful re-
moval of the benzoyl groups of 14a–c with
NaOMe in MeOH which afforded the free
nucleosides 15a–c in 89, 80, 95% yields, re-
spectively (Scheme 2).
Acetalation of 9b and 15a with acetone and
2,2-dimethoxypropane in the presence of p-
toluenesulphonic acid at room temperature
for 0.5 h afforded, after chromatographic
purification, the 2,3:4,5-diacetal derivatives 16
as oil (FABMS m/z 342 [MH]+; 364 [MNa]+)
in 65% yield and 17 as oil (FABMS m/z 493
[MH]+; 515 [MNa]+) in 78% yield (Scheme
3).
The structures of 14 and 15 were character-
ized from their HMQC NMR spectroscopic
study. The quaternary C-atoms of the diacetal
The structures of the nucleosides were de-
termined by homo and heteronuclear NMR
spectroscopic methods and by mass spectra.
groups of compound 14 at l 109.9 and 109.8
2/3
showed a
J
correlation to H-2%, H-3% and
CH
H-4%, H-5% at l 4.29, 4.03 and 4.07, 3.93,
respectively. Moreover, the 13C NMR of 14
showed a large difference in the chemical shift
(ꢀ11.0 ppm) between C-2%, C-3% and those of
the adduct 9a. The coupling constants in the
1
The H NMR spectra of 8a–d and 14a–c
showed a similar pattern, since H-1%, H-2% and
H-3% appeared, mostly, as multiplets, doublets
or a doublet of doublets in the region l 6.23–

70
N.A. Al-Masoudi et al. / Carbohydrate Research 318 (1999) 67–74
1H NMR spectra of the diacetals 14 and 15
between H-1%, H-2%, H-3% and H-4% are in the
range 7.0–8.0 Hz, confirming the expected
cis-configuration of these protons. These data
are in agreement with the results obtained from
(3×20 mL). The combined organic extracts
were dried (Na2SO4), filtered and evaporated to
dryness. The amorphous residue was purified
by column chromatography using first CHCl3
and then CHCl3/MeOH (19:1) as eluent.
1,5-Dimethyl-3-(1,2,3,4,5-penta-O-benzoyl-
the acetalation of the
D-manno series [32].
D
-manno-pentitol-1-yl)-1H-1,2,4-triazole (8a).
From 3a (0.55 g, 3.0 mmol). Yield: 1.19 g, 78%;
mp 70–77 °C (amorphous). lH (250 MHz,
CDCl3, 303 K): 8.12–7.84 (m, 10 H, ArH);
7.64–7.22 (m, 15 H, ArH); 6.45–6.36 (m, 3 H,
H-1%, H-2%, H-3%); 5.85 (m, 1 H, J4%,5¦ 5.8 Hz,
H-4%); 4.86 (dd, 1 H, J4%,5% 3.3 Hz, H-5%); 4.61 (dd,
1 H, J5%,5¦ 12.0 Hz, H-5¦); 3.49, 2.18 (2s, 6 H,
2CH3). Anal. Calcd for C44H37N3O10: 68.83; H,
4.86; N, 5.47; Found: C, 68.59; H, 4.69; N, 5.31.
m/z (FAB\0) 768 [MH+]; 790 [MNa+].
1 -Ethyl-5-methyl-3-(1,2,3,4,5-penta-O-ben-
3. Experimental
General methods.—Melting points are un-
corrected. NMR spectra were measured with
Bruker AC-250, WM-250 and 600 MHz (1H)
and at 62.9 MHz (13C) with TMS as internal
standard and on a l scale in ppm. EI and FAB
mass spectra were recorded on a MAT 312
mass spectrometer using 3-nitrobenzylalcohol
(NBOH) or glycerol as matrix. Some molecular
ions were detected by doping the samples with
Na+ ion. Column chromatography was per-
formed on SiO2 (for flash chromatography,
Merck). The cycloadditions were carried with
exclusion of moisture.
zoyl- -manno-pentitol-1-yl)-1H-1,2,4-triazole
D
(8b). From 3b (0.66 g, 3.0 mmol). Yield: 1.2 9
g, 83%; mp 66–72 °C (amorphous). lH (250
MHz, CDCl3, 303 K): 8.06–7.93 (m, 10 H,
ArH); 7.54–7.25 (m, 15 H, ArH); 6.44 (dd, 1
H, J3%,4% 8.9 Hz, H-3%); 6.39 (dd, 1 H, J2%,3% 1.2 Hz,
H-2%); 6.35 (d, 1 H, J1%,2% 9.0 Hz, H-1%); 5.89 (ddd,
1 H, J4%,5¦ 5.4 Hz, H-4%); 4.82 (dd, 1 H, J4%,5% 3.5
Hz, H-5%); 4.55 (dd, 1 H, J5%,5¦ 12.0 Hz, H-5¦);
3.82 (q, 2 H, J 7.0 Hz, CH2CH3); 2.22 (s, 3 H,
CH3); 1.09 (t, 3 H, CH2CH3). Anal. Calcd for
C45H39N3O10: 69.13; H, 5.03; N, 5.37. Found:
C, 68.74; H, 4.89; N, 5.28; m/z (FAB\0) 782
[MH+]; 804 [MNa+].
Preparation of acylated -glycosyl-1H-1,2,4-
triazole nucleosides 8 and 14
D
General procedure. A solution of SbCl5 (3.0
mmol) in CH2Cl2 (30 mL) was added dropwise
to a stirred, cooled (−60 °C) solution of the
sugar nitrile 5 (2.0 mmol) and the required
1-(chloroalkyl)azo compounds 3 (3.0 mmol) in
dry CH2Cl2 (20 mL). After stirring at −60 °C
for 1 h, then at 0 °C for 1 h and finally at 23 °C
for 10 min, pentane (50 mL) was added. The
residue was dissolved in CH3CN (40 mL). After
cooling to 0 °C, an aq solution of NaHCO3
(2.52 g, 30 mmol in 30 mL of H2O) was added
and the mixture was stirred at room tempera-
ture for 2 h. The organic solvent was evapo-
rated and the residue was extracted with CHCl3
1-Isopropyl-5 -methyl-3-(1,2,3,4,5-penta-O-
benzoyl- -manno-pentitol-1-yl)-1H-1,2,4-tri-
D
azole (8c). From 3c (0.72 g, 3.0 mmol). Yield:
1.2 g, 81%. mp 54–61 °C (amorphous). lH
(CDCl3, 303 K): 8.12–7.84 (m, 10 H, ArH);
7.61–7.24 (m, 15 H, ArH); 6.39–6.23 (m, 3 H,
Scheme 3.

N.A. Al-Masoudi et al. / Carbohydrate Research 318 (1999) 67–74
71
8.22–7.24 (m, 29 H, ArH); 6.40 (dd, 1 H,
J2%,3%=1.0 Hz, H-2%); 6.35 (dd, J3%,4% 8.2 Hz,
H-3%); 6.33 (d, 1 H, J1%,2% 8.8 Hz, H-1%); 5.80
(ddd, 1 H, J4%,5¦ 5.2 Hz, H-4%); 4.85 (dd, 1 H,
J4%,5% 3.5 Hz, H-5%); 4.50 (dd, 1 H, J5%,5¦ 12.3 Hz,
H-5¦); 2.30 (s, 3 H, CH3). lC (CDCl3): 165.2
(C-3); 151.4 (C-5); 133.9, 133.1, 130.1, 129.9,
128.4, 125.6, 124.5 (Ar); 70.7 (C-1%); 69.1 (C-
4%); 68.9 (C-3%); 65.4 (C-2%); 62.6 (C-5%). Anal
Calcd for C49H38N4O12: C, 67.27; H, 4.38; N,
6.40. Found: C, 66.92; H, 4.25; N, 6.19; m/z
(FABB0) 875 [MH+]; 931 [MNa+].
H-1%, H-2%, H-3%); 5.90 (ddd, 1 H, J4%,5¦ 5.5 Hz,
H-4%); 4.88 (dd, 1 H, J4%,5% 3.7 Hz, H-5%); 4.62
(dd, 1 H, J5%,5¦ 11.5 Hz, H-5¦); 4.52 [d, 1 H,
CH(CH3)2]; 2.23 (s, 3 H, CH3); 1.13 [d, 6 H, J
6.9 Hz, CH(CH3)2]. Anal. Calcd for
C46H41N3O10: C, 69.42; H, 5.19; N, 5.28.
Found: C, 69.08; H, 4.92; N, 5.12; m/z
(FAB\0) 796 [MH+]; 818 [MNa+].
6,7,8,9-Tetrahydro-2-(1,2,3,4,5-penta-O-benz-
oyl -
D
- manno - pentitol - 1 - yl) - 5H - 1,2,4-tri-
azolo-[1,5-a]azepine (8d). From 3d (0.79 g, 3.0
mmol). Yield: 1.14 g, 71%. mp 55–62 °C
(amorphous). lH (CDCl3, 600 MHz, HMQC,
ROSEY, 303 K): 8.0–7.94 (m, 10 H, ArH);
7.49–7.30 (m, 15 H, ArH); 6.42 (dd, 1 H, J3%,4%
8.0 Hz, H-3%); 6.38 (d, 1 H, J2%,3% 1.3 Hz, H-2%);
6.38 (d, 1 H, J1%,2% 7.8 Hz, H-1%); 5.87 (ddd, 1
H, H4%,5¦ 6.3 Hz, H-4%); 4.84 (dd, 1 H, J4%,5¦ 3.7
Hz, H-5%), 4.55 (dd, 1 H, J5%,5% 12.2 Hz, H-5¦);
3.97 (dt, 2 H, H-10a, H-10b); 2.72 (dt, 2 H,
H-6a, H-6b); 1.69 (m, 2 H, H-8a, H-8b); 1.54,
1.42 (m, 2 H, H-9a, H-9b); 1.44 (m, 2 H,
H-7a, H-7b). lC (CDCl3): 165.3, 165.2, 165.0,
164.9, 164.8 (CꢀO); 157.6 (C-3); 156.6 (C-5);
133.3, 133.0, 132.9, 130.0, 129.9, 129.8, 129.7,
129.5, 129.4, 129.2, 128.4, 128.3, 128.2, 128.1
(Ar); 70.9 (C-1%); 70.0 (C-4%); 69.3 (C-3%); 68.2
(C-2%); 62.8 (C-5%), 50.9 (C-10); 30.1 (C-8); 27.0
(C-9); 27.0 (C-6); 24.5 (C-7). Anal. Calcd for
C47H41N3O10: C, 69.88; H, 5.12; N, 5.20.
Found: C, 69.71; H, 5.06; N, 5.29; m/z
(FAB\0) 808 [MH+].
1-(4-Fluorophenyl)-3-methyl-5-(1,2,3,4,5-
penta-O-benzoyl- -manno-pentitol-1-yl)-1H-
D
1,2,4-triazole (14c). From 10c (0.73 g, 3.0
mmol). Yield: 1.16 g, 68%; mp 60–67 °C
(amorphous). lH (CDCl3, 303 K): 8.02–7.26
(m, 29 H, Ar); 6.40 (dd, 1 H, J2%,3% 1.3 Hz,
H-2%); 6.33 (dd, 1 H, J3%,4% 7.9 Hz, H-3%); 6.31
(d, 1 H, J1%,2% 8.6 Hz, H-1%), 5.78 (ddd, 1 H,
J4%,5¦ 5.3 Hz, H-4%); 4.82 (dd, 1 H, J4%,5% 3.4 Hz,
H-5%); 4.49 (dd, 1 H, J5%,5¦ 12.3 Hz, H-5¦); 2.38
(s,
3
H, CH3). Anal. Calcd for
C49H38NFN3O10: C, 69.44; H, 4.52; N, 4.96.
Found: C, 69.07; H, 4.43; N, 4.82; m/z
(FAB\0) 848 (MH+); 870 (MNa+).
Preparation of free nucleosides (9) and (15)
General procedure. A solution of acylated
nucleosides 8 and 14 (1.13 mmol) in 0.3 M
NaOMe (25 mL) was stirred at 23 °C for 18 h.
The solution was neutralized with 0.1 M HCl
and filtered. The filtrate was evaporated to
dryness and the residue was partitioned be-
tween water (30 mL) and Et2O (3×20 mL).
The aqeous layer was evaporated to dryness
and afterwards co-evaporated with EtOH
(3×20 mL). The residue was purified on SiO2
column using MeOH, in gradient (0–20%)
and CHCl3 as eluent. Evaporation of the ap-
propriate fractions afforded the pure nu-
cleosides 9 and 15.
3-Methyl-5-(1,2,3,4,5-penta-O-benzoyl- -
D
manno-pentitol-1-yl)-1-(2,4,6-trichlorophenyl)-
1H-1,2,4-traizole (14a). From 10a (0.98 g, 3.0
mmol). Yield: 1.18 g, 63%; mp 62–69 °C
(amorphous). lH (600 MHz, CDCl3, 303 K):
8.0–7.91 (m, 8 H, ArH); 7.56–7.25 (m, 19 H,
ArH); 6.70 (dd, 1 H, J2%,3% 1.2 Hz, H-2%); 6.60
(m, 2 H, H-3%, H-1%); 5.89 (dd, 1 H, J4%,5¦ 5.2
Hz, H-4%); 4.90 (dd, 1 H, J4%,5% 3.5 Hz, H-5%);
4.63 (dd, 1 H, J5%,5¦ 12.0 Hz, H-5¦); 2.38 (s, 3
H, CH3). Anal. Calcd for C49H36Cl3N3O10: C,
63.07; H, 3.89; N, 4.50. Found: C, 62.91; H,
3.82; N, 4.69; m/z (FAB\0) 932/934 [MH+];
954/956 [MNa+].
1,5 - Dimethyl - 3 - ( - manno-pentitol-1-yl)-
D
1-H1,2,4-triazole (9a). From 8a (0.87 g).
Yield: 0.23 g, 82%; mp 136–140 °C dec. lH
(600 MHz, D2O): 4.04 (d, 1 H, J1%,2% 9.1 Hz,
H-1%); 4.02 (dd, 1 H, J2%,3% 1.2 Hz, H-2%); 3.80
(dd, 1 H, J3%,4% 6.2 Hz, H-3%); 3.78 (ddd, 1 H,
J4%,5% 3.0 Hz, H-5%); 3.69 (s, 3 H, N–Me); 3.68
(dd, 1 H, J4%,5¦ 5.8 Hz, H-4%); 3.59 (dd, 1 H,
J5%,5¦ 12.1 Hz, H-5¦); 2.33 (s, 3 H, C5–Me). lC
(D2O): 161.5 (C-3); 154.4 (C-5); 70.6 (C-2%,
C-4%); 68.7 (C-3%); 66.4 (C-1%); 63.0 (C-5%); 34.6
3-Methyl-1-(4-nitrophenyl)-5-(1,2,3,4,5-pe-
nta-O-benzoyl- -manno-pentitol-1-yl)-1H-1,-
D
2,4-triazole (14b). From 10b (0.81 g, 3.0
mmol). Yield: 1.26 g, 72%; mp 65–72 °C
(amorphous). lH (600 MHz, CDCl3, 303 K):

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N.A. Al-Masoudi et al. / Carbohydrate Research 318 (1999) 67–74
1.59 (dt, 2 H, J 5.4 Hz; H-7a, H-7b). lC
(D2O): 161.0 (C-3); 159.2 (C-5); 71.6 (C-4%);
71.1 (C-2%); 69.2 (C-3%); 66.7 (C-1%); 63.1 (C-5%);
50.9 (C-10); 29.1 (C-8); 26.4 (C-9); 26.1 (C-6),
23.9 (C-7). Anal. Calcd for C12H21N3O5: C,
50.17; H, 7.37; N, 14.63. Found: C, 49.82; H,
7.29; N, 14.78; m/z (FAB\0) 288 [MH]+.
(N–Me); 10.6 (C5 –Me). Anal. Calcd. for
C9H17N3O5: C, 43.72; H, 6.93; N, 16.99.
Found: C, 43.52; H, 6.84; N, 16.86; m/z
(FAB\0) 248 [M+H]+; 270 [MNa]+.
1-Ethyl-5-methyl-3-( -manno-pentitol-1-yl)-
D
-1H-1,2,4-triazole (9b). From 8b (0.88 g).
Yield: 0.24 g, 81%.; mp 101–111 °C dec. lH
(600 MHz, D2O): 4.87 (d, 1 H, J1%,2% 8.7 Hz,
H-1%); 4.20 (q, 2 H, J 7.0 Hz, CH2CH3); 4.02
(dd, 1 H, J2%,3% 1.2 Hz, H-2%); 3.77 (dd, 1 H,
J3%,4% 8.6 Hz, H-3%); 3.74 (dd, 1 H, J4%,5% 2.8 Hz,
H-5%); 3.67 (ddd, 1 H, J4%,5¦ 6.2 Hz, H-4%); 3.59
(dd, 1 H, J5%,5¦ 11.8 Hz, H-5¦); 2.63 (s, 3 H,
C5–Me); 1.37 (t, 3 H, CH2CH3). lC (D2O):
155.9 (C-3); 151.3 (C-5); 70.6 (C-2%); 70.5 (C-
4%); 68.7 (C-3%); 65.5 (C-5%); 63.1 (C-1%); 45.0
(CH2CH3); 13.1, 9.3 (2Me). Anal. Calcd. for
C10H19N3O5: C, 45.97; H, 7.33; N, 16.08.
Found: C, 45.72; H, 7.19; N, 16.19; m/z
(FAB\0) 262 [MH]+; 284 [MNa]+.
5-(
D-manno-Pentitol-1-yl)-3-methyl-1-(2,4,-
6-trichlorophenyl)-1H-1,2,4-triazole
(15a).
From 14a (0.9 g). Yield: 0.35 g; 89%; mp
92–96 °C. lH (600 MHz, D2O): 7.92, 7.91
(AA%BB%, 2 H, ArH); 4.34 (dd, 1 H, J1%,2% 9.2
Hz, H-1%); 4.02 (dd, 1 H, J2%,3% 1.0 Hz, H-2%);
3.58 (dd, 1 H, J3%,4% 9.2 Hz, H-3%); 3.56 (dd, 1
H, J4%,5% 3.2 Hz, H-5%); 3.44 (dd, 1 H, J4%,5¦ 6.0
Hz, H-4%); 3.36 (dd, 1 H J5%,5¦ 11.1 Hz, H-5¦);
2.33 (s, 3 H, Me). lC (D2O): 159.6 (C-3); 159.4
(C-5); 135.8, 134.8, 134.4, 132.2, 125.9, 128.7
(Ar); 70.9 (C-4%), 70.8 (C-2%); 69.0 (C-3%); 65.0
(C-1%); 63.7 (C-5%); 13.5 (Me). Anal. Calcd for
C14H16Cl3N3O5: C, 40.75; H, 3.912; N, 10.18.
Found: C, 40.52; H, 3.83; N, 10.32; m/z
(FAB\0) 412/414 [MH]+; 434/436 [MNa]+.
1-Isopropyl-3-( -manno-pentitol-1-yl)-5-
D
methyl-1H-1,2,4-triazole (9c). From 8c (0.28
g); mp 125–132 °C. lH (600 MHz, D2O): 4.74
(d, 1 H, J1%,2% 9.0 Hz, H-1%); 4.08 (dd, 1 H, J2%,3%
1.2 Hz, H-2%); 3.79 (dd, 1 H, J3%,4% 6.0 Hz,
H-3%); 3.78 (dd, 1 H, J4%,5% 3.0 Hz, H-5%); 3.69
(ddd, 1 H, J4%,5¦ 6.4 Hz, H-4%); 3.58 (dd, 1 H,
J5%,5¦ 11.6 Hz, H-5¦); 2.37 (s, 3 H, C5–Me);
1.35 [d, 1 H, CH(Me)2]; 1.08 [t, 1 H,
CH(Me)2]. lC (D2O): 161.4 (C-3); 152.8 (C-5);
70.7 (C-2%); 70.6 (C-4%); 68.8 (C-3%); 66.1 (C-1%);
63.1 (C-5%); 50.3 [CH(Me)2]; 13.3 (C5–Me);
10.8, 10.6 [CH(Me)2]. Anal. Calcd. for
C11H21N3O5: C, 47.99; H, 7.69; N, 15.26.
Found; C, 47.72; H, 7.61; N, 15.45; m/z
(FAB\0) 276 [MH]+; 298 [MNa]+.
5-( -manno-Pentitol-1-yl)-3-methyl-1-(4-
D
nitrophenyl))-1H-1,2,4-triazole (15b). From
14b (0.9 g). Yield: 0.29 g; 80%; mp 121–
125 °C dec. lH (600 MHz, D2O): 7.47, 7.35
(AA%BB%, 4 H, ArH); 4.34 (d, 1 H, J1%,2% 9.1 Hz,
H-1%); 4.07 (dd, 1 H, J2%,3% 1.2 Hz, H-2%); 3.73
(dd, 1 H, J3%,4% 9.1 Hz, H-3%); 3.70 (dd, 1 H,
J4%,5% 3.9 Hz, H-5%); 3.68 (ddd, 1 H, J4%,5¦ 5.9 Hz,
H-4%); 3.63 (dd, 1 H, J5%,5¦ 11.2 Hz, H-5¦); 2.29
(s, 3 H, Me). lC (D2O): 160.7 (C-3); 154.5
(C-5); 147.0, 141.5, 125.4, 125. (Ar); 70.5 (C-
4%); 70.2 (C-2%); 68.5 (C-3%); 64.7 (C-1%); 63.9
(C-5%); 13.9 (Me). Anal. Calcd for
C14H18N4O7: C, 47.46; H, 5.12; N, 15.81.
Found: C, 47.09; H, 4.96; N, 15.92; m/z
(FAB\0) 355 [MH]+; 377 [MNa]+.
6,7,8,9-Tetrahydro-2-( -manno-pentitol-1-
D
yl)-5H-1,2,4-triazolo[1,5-a]azepine (9d). From
8d (0.79 g). Yield: 0.28 g, 90%; mp 78–82 °C.
lH (600 MHz, DMSO-d6): 5.09 (d, J1,OH 6.0
Hz, C1%–OH); 4.44 (d, J4%,OH 7.6 Hz, C4%–OH);
4.40 (dd, 1 H, J1%,2% 8.8 Hz, H-1%); 4.33 (t, J5%,OH
5.8 Hz, C5%–OH); 4.22 (d, J3%,OH 5.7 Hz, C3%–
OH); 4.16 (pt, 2 H, J 5.0 Hz, H-10a, H-10b);
3.99 (ddd, 1 H, J2%,3% 1.2 Hz, H-2%); 3.96 (d,
J2%,OH 7.4 Hz, C2% –OH); 3.65 (t, 1 H, J3%,4% 8.1
Hz, H-3%); 3.61 (dd, 1 H, J4%,5% 3.4 Hz, H-5%);
3.45 (m, 1 H, J4%,5¦ 5.7 Hz, H-4%); 3.38 (ddd, 1
H, J5%,5% 11.8 Hz, H-5¦); 2.84 (pt, 2 H, J 3.0 Hz,
H-6a, H-6b); 1.81 (pt, 2 H, J 5.6 Hz, H-8a,
H-8b); 1.68 (dt, 2 H, J 5.2 Hz, H-9a, H-9b);
1-(4-Fluorophenyl)-5-( -manno-pentitol-
D
1-yl)-3-methyl-1H-1,2,4-triazole (15c). From
14c (0.53 g). Yield: 0.19 g, 95%; mp 166–
170 °C dec. lH (600 MHz, D2O): 7.59, 7.33
(AA%BB%, 4 H, ArH); 4.97 (d, 1 H, J1%,2% 8.7 Hz,
H-1%); 4.16 (dd, 1 H, J2%,3% 1.1 Hz, H-2%); 3.72
(dd, 1 H, J3%,4% 9.1 Hz, H-3%), 3.70 (dd, 1 H,
J4%,5% 6.0 Hz, H-5%), 3.68 (ddd, 1 H, J4%,5¦ 2.7 Hz,
H-4%); 3.61 (dd, 1 H, J5%,5¦ 11.0 Hz, H-5¦); 2.45
(s, 3 H, Me). lC (D2O): 163.4 (d, J 246 Hz,
p-C); 156.6 (C-3); 155.7 (C-5); 116.8 (d, J 23
Hz, m-C); 128.1 (d, J 9.0 Hz, o-C); 131.0 (d, J

N.A. Al-Masoudi et al. / Carbohydrate Research 318 (1999) 67–74
73
Acknowledgements
3.0 Hz, i-C); 71.2 (C-4%); 70.4 (C-2%); 68.6 (C-3%);
63.8 (C-1%), 63.0 (C-5%); 11.2 (Me). Anal. Calcd.
for C14H18FN3O5: C, 51.37; H, 5.54; N, 12.84.
Found: C, 51.26; H, 5.49; N, 21.76; m/z
(FAB\0) 328 [MH]+; 350 [MNa]+.
The authors would like to thank Mrs M.J.
Quelle and Mr K. Ha¨gele, Fakulta¨t fu¨r Chemie,
Universita¨t Konstanz, Germany, for obtaining
the mass spectra and Mr A. Geyer, Fakulta¨t fu¨r
Chemie, Universita¨t Konstanz, Germany for
doing the 2-dimensional NMR-spectra.
1-Ethyl-3-(1,2:4,5-di-O-isopropylidene- -
D
manno-pentitol-1-yl)-5-methyl-1H-1,2,4-triaz-
ole (16).—To a stirred solution of 9b (100 mg,
0.40 mmol) in dry DMF (2 mL), dry acetone
(5 mL), dimethoxypropane (2 mL) and p-tolue-
nesulphonic acid (10 mg) were added. The
solution was stirred at room temperature for 30
min, neutralized with Na2CO3 and then evapo-
rated to dryness. The residue was partitioned
between CHCl3 (2×10 mL) and H2O (10 mL).
The combined organic extracts was dried
(Na2SO4), filtered and evaporated to dryness.
The residue was purified on short column of
SiO2. Elution with CHCl3–MeOH (95:5) af-
forded the pure acetal 16 (90 mg, 65%) as oil.
lH (600 MHz, CDCl3): 4.71 (d, 1 H, H J1%,2% 7.0
Hz, H-1%); 4.29 (t, 1 H, J2%,3% 7.0 Hz, H-2%); 4.10
(dd, 1 H, J5%,5¦ 13.5 Hz, H-5¦); 4.07 (dd, 1 H, J4%,5¦
5.0 Hz, H-4%); 4.03 (dd, 1 H, J3%,4% 7.0 Hz, H-3%);
4.02 (q, 2 H, J 7.0 Hz, CH2CH3); 3.93 (dd, 1
H, J4%,5% 7.0 Hz, H-5%); 2.38 (s, 3 H, C5–Me); 1.38
(t, 3 H, CH2CH3); 136, 1.30, 1.28, 1.27 [s, 12 H,
C(Me)2]. lC (CDCl3): 161.4 (C-3); 151.4 (C-5);
109.9, 109.8 (2quat-C); 81.2 (C-2%); 79.6 (C-3%);
76.4 (C-4%); 69.2 (C-1%); 67.1 (C-5%); 26.3, 27.1,
26.1, 25.1 [2C(Me)2)]; 11.1 (Me). Mass spec-
trum: m/z 341.4056 (C16H27N3O5 Anal. Calcd
m/z 341.4063 for M+).
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