Highly water soluble dyes based on pyrazolone derivatives of carbohydrates

Article abstract of DOI:10.1016/j.tet.2013.01.038

The synthesis of water soluble pyrazolone derivatives dyes was achieved. The pyrazolidin-3,5-dione 5a,b and pyrazolin-5-one 3a,b and 4a,b units were selected as the key building block to prepare the glycoconjugated H-chromophore 6a-d, 7a,b, azo 8a-d, 9a,b and bisazo 10a-d, 11a,b dyes pyrazolone derivatives based. The water solubility values show that these derivatives require a minimum percentage weight of 50% of the glycidic moiety to be water soluble and the ¹H and ¹³C data confirmed the tendency of pyrazolone derivatives dyes to exist in their OH tautomer form.

Full text of DOI:10.1016/j.tet.2013.01.038

Tetrahedron 69 (2013) 2239e2250
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Highly water soluble dyes based on pyrazolone derivatives of
carbohydrates
*
Jalal Isaad
University Lille Nord de France, Engineering and Textile Materials Laboratory, F-5900 Lille, France
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of water soluble pyrazolone derivatives dyes was achieved. The pyrazolidin-3,5-dione 5a,b
and pyrazolin-5-one 3a,b and 4a,b units were selected as the key building block to prepare the glyco-
conjugated H-chromophore 6aed, 7a,b, azo 8aed, 9a,b and bisazo 10aed, 11a,b dyes pyrazolone de-
rivatives based. The water solubility values show that these derivatives require a minimum percentage
weight of 50% of the glycidic moiety to be water soluble and the 1H and 13C data confirmed the tendency
of pyrazolone derivatives dyes to exist in their OH tautomer form.
Received 11 October 2012
Received in revised form 10 January 2013
Accepted 14 January 2013
Available online 21 January 2013
Keywords:
Sugar hydrazone
Pyrazolone
Ó 2013 Elsevier Ltd. All rights reserved.
Diazotization
Azopyrazolone
Water solubility
1. Introduction
Pyrazolones are a very important class of heterocycles due to
their biological and pharmacological activities,1 which exhibit anti-
inflammatory,2 herbicidal,3 fungicidal,4 and bactericidal,4 plant
growth regulating properties,3 antipyretic5 and protein kinase in-
hibitors.6 Moreover, these heterocycles are used as key starting
materials for the synthesis of commercial arylazopyrazolone dyes.
Many azopyrazolone dyes have been used as chromogenic reagents
for the colorimetric determinations7 and as indicators for com-
plexometric titrations.8 It was also demonstrated that some aryla-
zopyrazolone dyes have a potent antimicrobial activity.9 On the
other hand, it is well known that the most important commercial
application of pyrazolones is their use as good fastness dyestuffs for
wool, cotton, silk, leather, rubber and synthetic polyamides.10
The pyrazolin-5-one and pyrazolidine-3,5-dione were chosen for
their capacity to form an azo11 or triazene12 bond with another
pyrazolin-5-one or an aniline derivative. This reactional capacity is
due to the presence of hydrogen atom in the alpha position of the
carbonyl group of pyrazolin-5-one and pyrazolidine-3,5-dione de-
rivatives (Fig. 1).
Fig. 1. Structure of pyrazolidine-3,5-dione (1) and pyrazolin-5-one (2) derivatives.
dyeing13e17 and cyanide chemosensing18e22 applications. The glyco-
conjugation of the starting dyes was carried out using the external
spacer able to bond the saccharidic moiety to the starting dyes.13e17
In this paper, we report a new generation of water soluble syn-
theticdyesbasedonheterocyclicderivativecarbohydrates. Thesugar
pyrazolone derivatives (Fig. 2) were used as building blocks to form
heterocycle based chromophores including azoic dye classes 9aed,
10a,b, 11aed and 12a,b, and H-chromophore dyes 7aed and 8a,b
based on pyrazolidine-3,5-dione and pyrazolin-5-one derivatives.
The glycoconjugation process of the new water soluble hetero-
cyclic dyes does not need an external spacer to bond the sugar and
the starting dyes, but the spacer is a part of the dye through the
heterocyclic derivative carbohydrates (Fig. 3).
Recently, we have developed a new class of water soluble dyes
based on the mono or double-glycoconjugation of the starting dyes
(azoic, bis-azoic and antraquinonic) with a very common saccha-
ridedlactose and with its components galactose and glucose for
2. Results and discussion
2.1. Synthesis of the sugar pyrazolone derivatives
Saccharides were converted to their hydrazones23 by treatment
with aqueous hydrazine at room temperature as reported in
Scheme 1.
* Fax: þ33 (0)320272597; e-mail addresses: jalal.isaad@ensait.fr. jisaadjalal@
gmail.com.
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.01.038

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J. Isaad / Tetrahedron 69 (2013) 2239e2250
Fig. 2. General structure of the sugar pyrazolone derivatives.
An aldose or ketose hydrazone can exist either in an acyclic
hydrazone A, or in isomeric cyclic forms such as B, C, D, and E forms,
which can be considered to be sugar hydrazines (Scheme 2). As
previously reported in the literature,24,25 the aldose hydrazones are
formed initially as acyclic hydrazones form A that undergo slow
cyclization in unbuffered aqueous solution at pH>8. However, at
pH<7, the mixture equilibrated more rapidly, forming pre-
dominantly b-D-glycopyranosylhydrazine (form C), which is likely
to be hydrolyzed to the starting saccharide until a small quantity of
the isomeric form C compounds remained.
Scheme 1. Synthesis of the sugar pyrazolone derivatives. Reagents and conditions: (a)
aqueous hydrazine, rt, 12 h; (b) EtOH/H2O (pH¼6), reflux, 2 h; (c) 1. SOCl2, DCM, 2 h, rt,
2. THF, Et3N (pH¼6), rt, 12 h.
aqueous solutions of sugar hydrazone 2a,b (Scheme 1), which pro-
duced the coloured mixtures of isomeric heterocyclic derivatives
sugar products 3a,b and 4a,b. The conversion of sugar hydrazones to
sugar pyrazolidin-5-one derivatives is reported in Scheme 3. The
reaction conditions were optimized using different solvents. Thus
the reaction of ethyl acetoacetate or diethyloxalacetate with sugar
The sugar pyrazolidin-5-one derivatives were prepared by ad-
dition of ethyl acetoacetate or diethyloxalacetate to freshly prepared
Fig. 3. General structure of the prepared dyes.

J. Isaad / Tetrahedron 69 (2013) 2239e2250
2241
Table 1
Optimization of sugar pyrazolidin-5-one derivatives 3a and 3b synthesis
Compounds
Entry no.
Solvent/mixture
of solvent
Reaction
conditions
Yield (%)
3a
3a
3a
1
2
3
MeOH
EtOH
EtOH/H2O
Neutral
Neutral
33
49
88
Basic (NaOH/KOH,
pH¼6)
3a
3a
3a
3b
3b
3b
4
5
6
7
8
9
DMF
Neutral
29
31
47
35
46
84
MeOH/DMF (1:1)
EtOH/DMF (1:1)
MeOH
EtOH
EtOH/H2O
Neutral
Neutral
Neutral
Neutral
Basic (NaOH/KOH,
pH¼6)
3b
3b
3b
10
11
12
DMF
MeOH/DMF (1:1)
EtOH/DMF (1:1)
Neutral
31
34
43
Neutral
Neutral
Scheme 2. Plausible isomers of the glycosylhydrazines.
Scheme 3. Reaction pathways for the formation of sugar pyrazolidin-5-one derivatives from sugar hydrazone.
hydrazine using ethanol as solvent resulted in yields of 75e88% of
the corresponding sugar-based pyrazole derivatives (Table 1, entry
nos. 3, 9). During the course of the reaction, the hydrazone was
formed as an intermediate, which then subsequently cyclized and
underwent self-oxidation to furnish the expected pyrazole de-
rivatives. Indeed, the intermediates F1 and F2, equilibrate rapidly
with F3 and F6, and cyclize irreversibly to 3a,b, 4a,b and Faed,
respectively (Scheme 3). The absorption spectra of the sugar
pyrazolones separated by HPLC showed that the principal species
was the 5-pyrazolone isomer 3a,b, 4a,b as expected (Scheme 3),
but small amounts of the 3-pyrazolone isomers, Faed were also
present.
Following the results obtained and reported in Table 1, the best
sugardpyrazolin-5-one derivatives synthesis yields were obtained
with the polar and protic solvents (EtOH/water) and under basic pH
conditions, because the presence of polar and protic solvents helps
the hydrazine derivatives to dissolve and the presence of a mineral
base (NaOH or KOH) accelerates the condensation reaction
between the hydrazine and the ethyl acetoacetate or diethylox-
alacetate by the deprotonation of the hydrazine amine, which eases
its reaction with the carbonyl group of the ethyl acetoacetate or
diethyloxalacetate. On the other hand, hydrazinolysis of the
malonyl dichloride with hydrazine derivatives 2a,b in THF at pH 6,
affords the respective pyrazolidine-3,5-diones 5a,b in high yields as
reported in Scheme 4. The coupling reaction to obtain the corre-
sponding sugar pyrazolone derivatives was carried out at pH¼6, to
favour one isomer of sugar hydrazine derivative and therefore to
obtain predominantly one isomer of sugar pyrazolone derivatives,
b-D-glycopyranosylhydrazine as reported below. The proportions of
isomeric forms of the glycosylpyrazolones were monitored using
reversed-phase HPLC with diode array detection, and the results
are reported in Table 2.
The substituted 1H-pyrazolin-5-one (Fig. 4) presents three
tautomeric forms due to their ketoeenolic or lactamelactim tau-
tomerism, while the full aromatic enol form (OH tautomer) is the
predominant one (Fig. 4).

2242
J. Isaad / Tetrahedron 69 (2013) 2239e2250
5, CeOH). According to the areas of the signals in a quantitative 13
C
spectrum, there is about 92% of the OH tautomer and 8% of the NH
tautomer. Consequently, with the information available, the nature
of this tautomer cannot be unequivocally established; furthermore,
a rapid equilibrium NH/OH could be considered as well. In solid
phase sugar pyrazolones exist as either the NH or OH tautomer.
2.2. Synthesis of the sugar pyrazolone based azo dyes
The reaction pathways for the synthesis of the new dyes 10aed
and 11a,b are outlined in Scheme 5.
The diazotization reaction of 4-amino aniline in the presence of
NaNO2, and aqueous solution of HCl 1 N as solvent at 0 ꢀC gives the
corresponding bis-diazonium salts, which treated with sugar pyr-
azolidine-5-one 3a,b and 4a,b or sugar pyrazolidine-3,5-dione 5a,b,
already treated by sodium acetate affords the new azoic dyes
10aed and 11a,b in 90e94% yield.
On the other side, the treatment of the sugar pyrazolone de-
rivatives 3a,b, 4a,b and 5a,b with sodium nitrite in aqueous solu-
tion of concentrated HCl at 0 ꢀC affords the corresponding oxime
derivatives 30a,b, 40a,b and 50a,b. The reduction of the oxime group
of compounds 30a,b, 40a,b and 50a,b to the corresponding 4-amino
pyrazolones 300a,b, 400a,b and 500a,b is carried out in the presence of
zinc dust and ammonium chloride in methanol and under reflux for
several hours. Finally, the dyes 8aed and 9a,b are prepared in one
step from sugar pyrazolones 3a,b, 4a,b and 5a,b and the prepared
sugar 4-amino pyrazolones derivatives 300a,b, 400a,b and 500a,b in
high yields via diazotization reaction in the presence of sodium
nitrite in HCl solution (1 N) (Scheme 6).
The dyes 8aed, 9a,b, 10aed and 11a,b can exist as three tauto-
mers, azoketo form A, azo-enol form B and hydrazone-keto form C
as reported in our previous study.11 1H NMR spectroscopy of the
dyes 8aed, 9a,b, 10aed and 11a,b shows only peaks of aryl protons
(8.14e7.77 ppm), and a highly characteristic destabilized proton at
12.77 ppm for the hydrogen bond NeH peaks and there are no
signals in the 4e6 ppm region corresponding to the proton that
bears in the position C-4. These NMR data proved that the hydrazo-
keto tautomers form C are the synthesized dyes due to their sta-
bilization by intramolecular hydrogen bond, where the hydrogen
Scheme 4. Reaction pathways for the formation of sugar pyrazolidin-3,5-dione de-
rivatives from sugar hydrazone.
Table 2
Proportions of cyclic isomers of 1-glycosylpyrazolones (%)
a
Furanosyl-
b
Furanosyl-
a
Pyranosyl-
b Pyranosyl-
3a
3b
4a
4b
5a
5b
2
0
3
0
3
0
4
0
5
0
4
0
5
11
5
10
4
9
89
89
87
90
89
91
Fig. 4. Tautomerism of the sugar pyrazolin-5-one derivatives.
This phenomenon is confirmed by 13C NMR spectra as reported
in Table 3.
All compounds show several signals that correspond to only one
tautomer in that solvent. A signal at about 87 ppm, which according
to the DEPT spectrum corresponds to a CH group is assigned to C-4.
The corresponding proton resonance appears at 6.06 ppm (s, 1H) in
the 1H NMR spectrum. This information rules out the CO tautomer.
The signal of about 162 ppm corresponds to C-5, but to assign it as
a C]O or CeOH is not straightforward. For this reason, the 13C NMR
was carried out at different concentrations in DMSO-d6 as solvent.
For 3a the 13C NMR spectra in DMSO-d6 presents 10 downfall signals
(for the pyrazolidin-5-onic moiety) that correspond to 2 tautomers.
There is one signal at 161.0 ppm (C-5, C]O) and another at 152.5 (C-
Table 3
13C NMR data of the pyrazolidin-5-onic moiety of compounds 3a,b and 4a,b realized
in DMSO-d6
C3
C4
C5
3a
3b
4a
4b
147.7
147.7
142.3
142.3
87.2
87.1
90.5
90.4
152.2
152.3
152.6
152.6
Scheme 5. Synthetic sequences for dyes 10aed and 11a,b. Reagents and conditions:
(a) 1. sodium acetate, THF/H2O, 2. NaNO2, HCl 1 N, H2O, 0 ꢀC, rt, 12 h, 90e94%.

J. Isaad / Tetrahedron 69 (2013) 2239e2250
2243
Scheme 6. Synthetic sequences for dyes 8aed and 9a,b. Reagents and conditions: (a) NaNO2, HCl 1 N, H2O, 0 ꢀC, 10 h; (b) Zn, MeOH, NH4Cl, reflux, 4 h; (c) NaNO2, HCl 37%, H2O, 0 ꢀC,
rt, 12 h.
bears by the NeH bond is stabilized by the oxygen of one of both
carbonyl groups present in the pyrazolone moiety, which confirms
our previous results11 (Fig. 5).
systems are called ‘H-chromophore’ due to its structural geome-
try.26 The synthesis of the H-chromophore dyes 6aed and 7a,b is
showed in Scheme 7.
To obtain the desired merocyanine dyes 6aed and 7a,b (Fig. 3),
glycoconjugated pyrazolidine-3,5-dione (1) and pyrazolin-5-one (2)
derivatives 3a,b, 4a,b and 5a,b (Fig. 2) were chosen as the building
2.3. Synthesis of the H-chromophore dyes 6aed and 7a,b
The H-chromophore dyes are C]C double bond substituted by
two opposing donor and acceptor groups. These donoreacceptor
Scheme 7. Synthesis for the H-chromophore dyes 16aed and 7a,b. Reagents and
Fig. 5. Stable tautomer form of the 8aed, 9a,b, 10aed and 11a,b.
conditions: (a) AcOH, Br2, 0 ꢀC, rt, 12 h; (b) NaH, THF, rt, 0.5 h.

2244
J. Isaad / Tetrahedron 69 (2013) 2239e2250
blocks. The pyrazolidin-3,5-dione 5a,b and pyrazolin-5-one 3a,b
and 4a,b units were activated by the treatment of these compounds
by 2 equiv of sodium hydride to deprotonate the C4 of these de-
rivatives, to form their corresponding enolate ions as an electron
donor. On the other hand, the di-bromination of the same pyr-
azolidin-3,5-dione 5a,b and pyrazolin-5-one 3 and 4a,b with Br2
under acidic conditions yield the di-bromo-pyrazolidine-3,5-dione
12a,b and di-bromo-pyrazolidine-5-dione 13a,b and 14a,b as elec-
tron acceptors. Finally, the new H-chromophore dyes 6aed and 7a,b
weresynthesized bythe coupling stepof the bis-carbanionswith the
4,4-dibrominated derivatives as shown in Scheme 7 in high yields.
2.4. Water solubility of the prepared dyes
With all these sugar pyrazolone based azo dyes 6aed, 7a,b,
8aed, 9a,b, 10aed and 11a,b, we can compare their solubility in
water and their glycidic content (Table 4).
The water solubility is immediate with the all dyes except the
dyes 10a and 11a, which are insoluble and poorly soluble, re-
spectively, in water. Therefore we can conclude that for these de-
rivatives to be soluble, a minimum percentage weight of 50% of the
glycidic moiety is required, whereas at 42% they are completely
insoluble.
Table 4
Formulae of the prepared dyes and the molecular weights of their lipophilic
(chromophore) and glycidic moieties (saccharide) and their molecular weight ratios
and solubility
Dyes
Chromophore
(formula
weight)
Saccharide
(formula
weight)
MW [g/mol]
Ratio
saccharide
/MW [%]
Solubility
Fig. 6. General structure of the in-glycoconjugated dyes 15a,b, 16, 17a,b, 18, 19a,b, 20.
[a][g/L]a
extinction coefficient values can be considered almost constant,
only very small differences being detected. Thus, the presence of
the carbohydrates on the dyes 6aed, 7a,b, 8aed, 9a,b, 10aed and
11a,b does not affect the UV/vis spectrum as these carbohydrates
are far from the chromophore. Very small changes are apparent in
the spectra of compounds.
6a
6b
6c
6d
7a
7b
8a
8b
8c
8d
9a
9b
10a
10b
10c
10d
11a
C12H10N4O6
C8H6N4O2
C12H10N4O6
C8H6N4O2
C6H2N4O4
C6H2N4O4
C12H12N6O6
C8H8N6O2
C12H12N6O6
C8H8N6O2
C6H4N6O4
C6H4N6O4
C18H16N8O6
C14H12N8O2
C18H16N8O6
C12H22O10
C12H22O10
C24H42O20
C24H42O20
C12H22O10
C24H42O20
C12H22O10
C12H22O10
C24H42O20
C24H42O20
C12H22O10
C24H42O20
C12H22O10
C12H22O10
C24H42O20
C24H42O20
C12H22O10
C24H32N4O16
C20H28N4O12
C36H52N4O26
C32H48N4O22
C18H24N4O14
C30H44N4O24
C24H34N6O16
C20H30N6O12
C36H54N6O26
C32H50N6O22
C18H26N6O14
C30H46N6O24
C30H38N8O16
C26H34N8O12
C42H58N8O26
C38H54N8O22
C24H30N8O14
51.58
63.17
67.99
77.38
62.69
70.01
49.24
59.69
65.99
74.71
59.27
74.37
42.55
50.15
59.63
66.73
49.84
45.4
45.8
57.6
57.1
43.3
43.9
42.2
42.4
55.6
55.3
37.5
46.2
Insoluble
31.4
38.9
Table 5
UV/vis absorption spectra of the dyes 6aed, 7a,b, 8aed, 9a,b,10aed and 11a,b and of
their not glycoconjugated 15a,b, 16, 17a,b, 18, 19a,b, 20
Dyes
lmax (MeOH) [nm]
3
(max)/Mꢁ1 cmꢁ1
6a
6b
6c
6d
7a
7b
8a
8b
8c
8d
9a
9b
10a
10b
10c
10d
11a
11b
15a
15b
16
17a
17b,
18
19a
19b
20
506
494
507
494
511
511
424
401
424
401
456
455
396
371
396
370
416
415
505
495
510
425
400
456
397
372
416
32,745
31,698
32,739
31,701
35,615
35,608
29,467
28,043
29,455
28,011
30,613
30,598
27,264
25,736
27,241
25,699
30,156
30,129
32,754
31,672
35,622
29,412
28,009
30,624
27,257
25,747
30,169
C14H12N8O2
39.1
C12H8N8O4
Poorly
soluble
40.4
11b
C12H8N8O4
C24H42O20
C36H50N8O24
66.42
a
The solubility was measured at rt.
2.5. UV/vis study
UV/vis absorption spectra of the newly generated water soluble
dye based on carbohydrates 6aed, 7a,b, 8aed, 9a,b, 10aed and
11a,b were studied and compared to their corresponding dyes
without carbohydrates 15a,b, 16, 17a,b, 18, 19a,b, 20 (Fig. 6) because
the glycoconjugated dyes should display the same colour as the no
glycoconjugated materials 15a,b, 16, 17a,b, 18, 19a,b, 20 if the
chromophore is not affected by the glycoconjugation process. The
UV/vis spectra of the dyes 15a,b, 16, 17a,b, 18, 19a,b, 20 and the
glycoconjugated dyes 6aed, 7a,b, 8aed, 9a,b, 10aed and 11a,b in
diluted MeOH solutions (10ꢁ5 M) are reported in Table 4.
The results reported in Table 5 show that lmax does not exhibit
any significant shift between the no glycoconjugated dyes and the
glycoconjugated derivatives with glycide units. Also, molar

J. Isaad / Tetrahedron 69 (2013) 2239e2250
2245
3. Conclusion
1 mL/min with 84:16 acetonitrile/water. Elemental analyses were
recorded on a Perkin Elmer 240 C Elemental Analyzer. The sugar
hydrazone was prepared following the procedure reported in the
literature.23
A convenient approach to water soluble pyrazolone derivative
based dyes has been reported by using the glycoconjugated pyr-
azolone derivatives as a building block to form the desired dyes.
The glycoconjugation process of the new water soluble heterocyclic
dyes does not need an external spacer to bond the carbohydrates
and the starting dyes, but the spacer is a part of the dye through the
heterocyclic derivative carbohydrates. The final glycoconjugated
species were quite water soluble and the water solubility of dyes
depends on the molecular weight of the lipophilic portion in the
final molecule, The pyrazolones presented offer the opportunity to
introduce two units of carbohydrates, as we recently reported for
commercial disperse dyes.16 Currently, tinctorial tests of these new
dyes are under investigation on synthetic and natural textiles. But
the glyconjugation process here illustrated can be usefully applied
to the pyrazolone-based derivatives in general, so that the property
of water solubility can be easily reached with this kind of
derivatives.
4.2. General procedure A: synthesis of the sugar pyrazolidin-
5-dione derivatives (3a,b and 4a,b)
The freshly prepared sugar hydrazone 2a,b (1 equiv) was dis-
solved in 1:3 MeCN/water (20 mL) then purged with argon, and
ethyl acetoacetate or diethyloxalacetate (1 equiv) was added. Argon
is bubbled through the mixture for a further 3 h, and the sample
was lyophilized to yield 3a,b or 4a,b as a yellow powder.
4.2.1. 3-Methyl-1-((3S,4S,5S)-3,4,5-trihydroxy-6-(hydroxymethyl)
tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5(4H)-one (3a). The product
3a was prepared following the general procedure A using the fol-
lowing amounts: ethyl acetoacetate (1.00 g, 7.96 mmol), 1-glucosyl
hydrazine (1.49 g, 7.96 mmol) to yield 3a (1.88 g, 94% yield) as
a yellow solid as a mixture of
(200 MHz, Me2SO):
a- and b
-pyranosic anomers. 1H NMR
¼11.48 (s, OH), 6.12 (s, 1H, pyrC4H), 5.28e5.22
4. Experimental section
d
(d, 1H), 3.81e3.60 (m, 4H), 3.48e3.34 (m, 2H), 2.32 (s, 3H, pyrCH3).
4.1. Chemicals and materials
13C NMR (50 MHz, Me2SO): see Table 6 in Supplementary data for
the glycidic part and
d
¼152.2, 147.7, 87.2, 13.9 ppm. MS (ESI): m/
All chemicals were reagent grade (Aldrich Chemical Co.) and
were used as purchased without further purification. Thin layer
chromatography (TLC) analysis was performed using Fluka alu-
minium foils coated with 25 mm particle size silica gel matrix
F254. TLC development involved either UV (254 and 366 nm) or
visible light inspection, followed by either treatment with an acid
solution of p-anisaldehyde or a basic solution of KMnO4 and
heating. Flash column chromatography was performed on Merck
silica gel 60 (particle size 0.040e0.063 nm, 230e400 mesh ASTM)
according to the procedure of Still.27 Melting points were recorded
on a Melting Point Apparatus SMP3-STUART SCIENTIFIC. Optical
rotations were measured on a Jasco DIP-370 polarimeter using
a 100 mm path-length cell at 589 nm. UV/vis spectra were
recorded on a Cary-4000 Varian spectrophotometer, using either
0.1 or 1 cm quartz cuvette. Infrared spectra were recorded in a KBr
disk on a Perkin Elmer-Spectrum BX FTIR system. Absorptions are
quoted in wavenumbers (cmꢁ1). 1H NMR and 13C NMR spectra
were recorded at 200 MHz 1H (50.0 MHz 13C) on a Varian Gemini
z¼261.31 [Mþ1]þ. C10H16N2O6 (260.10): calcd C, 46.15; H, 6.20; N,
10.76; found: C, 46.31; H, 6.39; N, 10.81.
4.2.2. (2S,3R,4S,5R,6R)-2-((3S,4R,5S)-4,5-Dihydroxy-6-(5-hydroxy-
3-methyl-1H-pyrazol-1-yl)-2-(hydroxymethyl)tetrahydro-2H-pyran-
3-yloxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol
(3b). The product 3b was prepared following the general pro-
cedure A using the following amounts: ethyl acetoacetate (1.00 g,
7.96 mmol), 1-lactosyl hydrazine (2.82 g, 7.96 mmol) to yield 3b
(3.12 g, 93% yield) as a yellow solid as a mixture of
a
- and
b-pyr-
anosic anomers. 1H NMR (200 MHz, Me2SO):
d
¼11.51 (s, OH, both
anomers), 6.14 (s, 1H, pyrC4H, both anomers), 5.10e4.55 (m, 2H,
both anomers), 4.31e4.16 (m, 4H, both anomers), 3.88e3.79 (m, 6H,
both anomers), 3.44e3.41 (m, 2H, both anomers), 2.31 (s, 3H,
pyrCH3). 13C NMR (50 MHz, Me2SO): see Table 7 in Supplementary
data for the glycidic part and
d
¼152.3, 147.7, 87.1, 13.7 ppm. MS
(ESI): m/z¼423.27 [Mþ1]þ. C16H26N2O11 (422.15): calcd C, 45.50; H,
6.20; N, 6.63; found: C, 45.61; H, 6.27; N, 6.77.
spectrometer. Spin resonances are reported as chemical shifts (d)
in parts per million (ppm) and referenced to the residual peak as
an internal standard of the solvent employed, as follows: CDCl3
7.27 ppm (1H NMR), 77 ppm (13C NMR, central band), DMSO-d6
2.50 ppm (1H NMR, central band), 39.5 ppm (13C NMR, central
band). Spin multiplicity is showed by s¼singlet, d¼doublet,
t¼triplet, q¼quartet, m¼multiplet, br¼broad. Coupling constants J
are reported in hertz (Hz). Mass spectra were recorded on
a ThermoScientific LCQ-Fleet mass spectrometer under electro-
spray ionization (ESI, þc or ꢁc technique). High resolution mass
spectra (HRMS) were recorded on an LTP-Orbitrap mass spec-
trometer from Thermo Electron Corporation under ESI (þc) tech-
nique. Mass spectrometric analysis is quoted in the m/z form.
Preparative reversed-phase high-performance liquid chromato-
graphic (RP-HPLC) purification of compounds was carried out
using a Jordi divinylbenzene column (100ꢂ10 mm, Alltech, Deer-
field, USA) with detection at 220 and 240 nm using a Shimadzu
series 10 HPLC system. The elution conditions were adjusted to
suit each monosaccharide. For example, monosaccharide pyr-
azoles were separated by elution at 1.5 mL/min with 13:87 ace-
tonitrile/water for 8 min, a gradient to 25:75 over 12 min, then to
60:40 over 6 min. Disaccharide pyrazoles were fractionated by
4.2.3. Ethyl 5-hydroxy-1-((3S,4S,5S)-3,4,5-trihydroxy-6-(hydroxymet-
hyl)tetrahydro-2H-pyran-2-yl)-1H-pyrazole-3-carboxylate (4a). The
product 4a was prepared following the general procedure A using the
following amounts: diethyloxalacetate (1.00 g, 5.32 mmol), 1-
glucosyl hydrazine (1.03 g, 5.32 mmol) to yield 4a (1.59 g, 94%
yield) as a yellow solid as a mixture of
a- and b-pyranosic anomers.
1H NMR (200 MHz, Me2SO):
d¼11.46 (s, OH), 7.07 (s, 1H, pyrC4H),
5.28e5.21 (d, 1H), 4.28 (q, J¼7.00 Hz, 2H, CH2), 3.81e3.61 (m, 4H),
3.47e3.34 (m, 2H), 1.28 (t, J¼7.00 Hz, 3H, CH3). 13C NMR (50 MHz,
Me2SO): see Table 6 in Supplementary data for the glycidic part and
d
¼161.3, 152.6, 142.3, 90.5, 60.1, 14.2 ppm. MS (ESI): m/z¼319.22
[Mþ1]þ. C12H18N2O8 (318.11): calcd C, 45.28; H, 5.70; N, 8.80; found:
C, 45.36; H, 5.79; N, 8.88.
4.2.4. Ethyl 1-((3S,4R,5S)-3,4-dihydroxy-6-(hydroxymethyl)-5-((2S,3R,
4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-
yloxy)tetrahydro-2H-pyran-2-yl)-5-hydroxy-1H-pyrazole-3-
carboxylate (4b). The product 4b was prepared following the general
procedure A using the following amounts: diethyloxalacetate (1.00 g,
5.32 mmol), 1-lactosyl hydrazine (1.89 g, 5.32 mmol) to yield 4b
(2.42 g, 95% yield) as a yellow solid as a mixture of
anomers. 1H NMR (200 MHz, Me2SO):
¼11.52 (s, OH, both anomers),
7.14 (s, 1H, pyrC4H, both anomers), 5.11e4.55 (m, 2H, both anomers),
a- and b-pyranosic
normal-phase HPLC on
a
5/
m
m
aminopropylsilica column
d
(220ꢂ4.6 mm, Brownlee, Foster City, USA), eluted isocratically at

2246
J. Isaad / Tetrahedron 69 (2013) 2239e2250
4.29 (q, J¼6.8 Hz, 2H, CH2), 4.25e4.14 (m, 4H, both anomers),
3.88e3.78 (m, 6H, both anomers), 3.44e3.40 (m, 2H, both anomers),
1.28 (t, J¼6.8 Hz, 3H, CH3). 13C NMR (50 MHz, Me2SO): see Table 7 in
C9H12Br2N2O7 (417.82): calcd C, 25.74; H, 2.88; N, 6.67; found: C,
25.81; H, 2.95; N, 6.77.
Supplementary data for the glycidic part and
d¼161.2, 152.6, 142.3,
4.4.2. 4,4-Dibromo-1-((3R,5S)-3,4-dihydroxy-6-(hydroxymethyl)-5-
((3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2H-
pyran-2-yloxy) tetrahydro-2H-pyran-2-yl) pyrazolidine-3,5-dione
(12b). The product 12b was prepared according to the general
procedure C using the following amounts: 5b (1.00 g, 2.35 mmol),
bromine (0.27 mL, 4.70 mmol) in acetic acid (15 mL) to afford 12b
90.4, 60.2, 14.2 ppm. MS (ESI): m/z¼481.26 [Mþ1]þ. C18H28N2O13
(480.15): calcd C, 45.00; H, 5.87; N, 5.83; found: C, 45.16; H, 5.94; N,
5.89.
4.3. General procedure B: synthesis of the sugar pyrazolidine-
3,5-dione derivatives (5a,b)
(1.28 g, 94%) as a coloured solid as a mixture of
a
- and
b-pyranosic
anomers. 1H NMR (200 MHz, Me2SO):
d¼5.11e4.55 (m, 2H, both
anomers), 4.30e4.16 (m, 4H, both anomers), 3.88e3.79 (m, 6H,
both anomers), 3.44e3.41 (m, 2H, both anomers) ppm. 13C NMR
(50 MHz, Me2SO): see Table 7 in Supplementary data for the gly-
Malonic acid (1 equiv) and sugar hydrazine derivative (1 equiv)
were suspended in methanol (approximate concn 0.2 M) under
argon atmosphere and stirred for 2 h at 80 C. Afterwards, the so-
lution was lyophilized to yield 5a,b as a yellow powder.
cidic part and
d
¼170.4, 168.7, 93.8 ppm. MS (ESI): m/z¼581.11
[Mþ1]þ. C15H22Br2N2O12 (579.94): calcd C, 30.95; H, 3.81; N, 4.81;
found: C, 31.08; H, 3.93; N, 4.97.
4.3.1. 1-((3S,4S,5S)-3,4,5-Trihydroxy-6-(hydroxymethyl)tetrahydro-
2H-pyran-2-yl)pyrazolidine-3,5-dione (5a). The product 5a was
prepared following the general procedure B using the following
amounts: malonic acid (2.00 g, 19.23 mmol), glucose hydrazine
(3.73 g, 19.23 mmol) to yield 5a (4.73 g, 94% yield) as a yellow solid
4.4.3. 4,4-Dibromo-3-methyl-1-((3R,5S)-3,4,5-trihydroxy-6-(hydrox-
ymethyl)tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5(4H)-one
(13a). The product 13a was prepared according to the general
procedure C using the following amounts: 3a (1.00 g, 2.41 mmol),
bromine (0.25 mL, 4.82 mmol) in acetic acid (15 mL) to afford 13a
as a mixture of
Me2SO):
¼5.28e5.21 (d, 1H), 3.81e3.61 (m, 4H), 3.47e3.34 (m,
2H), 3.08 (s, 2H, CH2). 13C NMR (50 MHz, Me2SO): see Table 6 in
a- and b
-pyranosic anomers. 1H NMR (200 MHz,
d
(0.95 g, 95%) as a coloured solid as a mixture of
a- and b-pyranosic
anomers. 1H NMR (200 MHz, Me2SO):
d
¼5.29e5.21 (d, 1H),
Supplementary data for the glycidic part and
d
¼170.1, 169.2,
3.81e3.61 (m, 4H), 3.47e3.30 (m, 2H), 2.01 (s, 3H, CH3ePyr) ppm.
46.9 ppm. MS (ESI): m/z¼263.28 [Mþ1]þ. C9H14N2O7 (262.06):
13C NMR (50 MHz, Me2SO): see Table 6 in Supplementary data for
calcd C, 41.22; H, 5.38; N, 10.68; found: C, 41.31; H, 5.44; N, 10.78.
the glycidic part and
d
¼171.6, 156.7, 75.6, 17.4 ppm. MS (ESI): m/
z¼416; 13 [Mþ1]þ. C10H14Br2N2O6 (415; 91): calcd C, 28.73; H, 3.38;
4.3.2. 1-((3S,4R,5S)-3,4-Dihydroxy-6-(hydroxymethyl)-5-((3R,4S,5R,
6R)-3,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2H-pyran-2-
yloxy)tetrahydro-2H-pyran-2-yl) pyrazolidine-3,5-dione (5b). The
product 5b was prepared following the general procedure B using
the following amounts: malonic acid (2.00 g, 19.23 mmol), lactose
hydrazine (6.84 g, 19.23 mmol) to yield 5b (7.74 g, 95% yield) as
N, 6.70; found: C, 28.86; H, 3.44; N, 6.81.
4.4.4. 4,4-Dibromo-1-((3R,5S)-3,4-dihydroxy-6-(hydroxymethyl)-5-
((3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-
pyran-2-yloxy)tetrahydro-2H-pyran-2-yl)-3-methyl-1H-pyrazol-
5(4H)-one (13b). The product 13b was prepared according to the
general procedure C using the following amounts: 3b (1.00 g,
2.36 mmol), bromine (0.24 mL, 4.72 mmol) in acetic acid (15 mL)
a yellow solid as a mixture of
(200 MHz, Me2SO):
(m, 4H, both anomers), 3.88e3.78 (m, 6H, both anomers),
3.44e3.40 (m, 2H, both anomers), 3.09 (s, 2H, CH2). 13C NMR
(50 MHz, Me2SO): see Table 7 in Supplementary data for the gly-
a- and b
-pyranosic anomers. 1H NMR
¼5.11e4.55 (m, 2H, both anomers), 4.25e4.14
d
to afford 13b (1.30 g, 96%) as a coloured solid as a mixture of
a-
and
b
-pyranosic anomers. 1H NMR (200 MHz, Me2SO):
d
¼5.10e4.55 (m, 2H, both anomers), 4.31e4.15 (m, 4H, both
cidic part and
d
¼170.2, 169.2, 47.0 ppm. MS (ESI): m/z¼425.33
anomers), 3.89e3.79 (m, 6H, both anomers), 3.44e3.40 (m, 2H,
both anomers), 2.02 (s, 3H, CH3ePyr) ppm. 13C NMR (50 MHz,
Me2SO): see Table 7 in Supplementary data for the glycidic part
[Mþ1]þ. C15H24N2O12 (424.12): calcd C, 42.45; H, 5.70; N, 6.60;
found: C, 42.53; H, 5.76; N, 6.68.
and
d
¼171.7, 156.7, 75.5, 17.6 ppm. MS (ESI): m/z¼579.17 [Mþ1]þ.
4.4. General procedure C: synthesis of the 4,4-dibromo pyr-
azolidine-3,5-dione and pyrazolidin-5-dione derivatives
(12a,b, 13a,b, 14a,b)
C16H24Br2N2O11 (577.97): calcd C, 33.12; H, 4.17; N, 4.83; found: C,
33.18; H, 4.25; N, 4.93.
4.4.5. Ethyl 4,4-dibromo-5-oxo-1-((3R,5S)-3,4,5-trihydroxy-6-(hy-
droxymethyl)tetrahydro-2H-pyran-2-yl)-4,5-dihydro-1H-pyrazole-3-
carboxylate (14a). The product 14a was prepared according to the
general procedure C using the following amounts: 4a (1.00 g,
3.14 mmol), bromine (0.32 mL, 6.28 mmol) in acetic acid (15 mL) to
To a suspension of sugar pyrazolidine-3,5-dione or sugar pyr-
azolidine-5-dione derivatives (1 mmol) in acetic acid (10 mL), Br2
(2 mmol) was added at 0 ꢀC and the resulting mixture was stirred at
room temperature for 2 h. Excess of the bromine and the acetic acid
were removed under reduced pressure and the resulting colourless
oil was dried for 10 min by vacuum suction and used as-is without
purification.
afford 14a (0.95 g, 95%) as a coloured solid as a mixture of
a
- and
b-
pyranosic anomers. 1H NMR (200 MHz, Me2SO):
d
¼5.28e5.22 (d,
1H), 4.26 (q, J¼6.9 Hz, 2H, CH2), 3.82e3.61 (m, 4H), 3.47e3.30 (m,
2H), 1.28 (t, J¼6.9 Hz, 3H, CH3) ppm. 13C NMR (50 MHz, Me2SO): see
4.4.1. 4,4-Dibromo-1-((3R,5S)-3,4,5-trihydroxy-6-(hydroxymethyl)
tetrahydro-2H-pyran-2-yl)pyrazolidine-3,5-dione (12a). The prod-
uct 12a was prepared according to the general procedure C using
the following amounts: 5a (1.00 g, 3.80 mmol), bromine
(0.44 mL, 7.60 mmol) in acetic acid (15 mL) to afford 12a (1.03g,
Table 6 in Supplementary data for the glycidic part and
d
¼171.9,
164.1, 149.6, 69.2, 60.6, 14.3 ppm. MS (ESI): m/z¼475.16 [Mþ1]þ.
C12H16Br2N2O8 (473.93): calcd C, 30.27; H, 3.39; Br, 33.57; N, 5.88;
found: C, 30.33; H, 3.43; Br, 33.64; N, 5.95.
95%) as a coloured solid as a mixture of
a
- and
b
-pyranosic
4.4.6. Ethyl4,4-dibromo-1-((3R,5S)-3,4-dihydroxy-6-(hydroxymethyl)-
5-((3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-
pyran-2-yloxy)tetrahydro-2H-pyran-2-yl)-5-oxo-4,5-dihydro-1H-pyr-
azole-3-carboxylate (14b). The product 14b was prepared according
to the general procedure C using the following amounts: 4b (1.00 g,
anomers. 1H NMR (200 MHz, Me2SO):
d
¼5.28e5.22 (d, 1H),
3.82e3.61 (m, 4H), 3.47e3.31 (m, 2H). 13C NMR (50 MHz, Me2SO):
see Table 6 in Supplementary data for the glycidic part and
d
¼170.3, 168.7, 93.9 ppm. MS (ESI): m/z¼418.94 [Mþ1]þ.

J. Isaad / Tetrahedron 69 (2013) 2239e2250
2247
2.08 mmol), bromine (0.21 mL, 4.16 mmol) in acetic acid (15 mL) to
afford 14b (1.70 g, 97%) as a coloured solid as a mixture of - and
pyranosic anomers.1H NMR (200 MHz, Me2SO):
¼5.10e4.55 (m, 2H,
(275.11): calcd C, 43.63; H, 6.23; N, 15.27; found: C, 43.72; H, 6.31;
N, 15.34.
a
b-
d
both anomers), 4.25 (q, J¼6.6 Hz, 2H, CH2), 4.32e4.16 (m, 4H, both
anomers), 3.87e3.77 (m, 6H, both anomers), 3.44e3.41 (m, 2H, both
anomers),1.27 (t, J¼6.6 Hz, 3H, CH3) ppm. 13C NMR (50 MHz, Me2SO):
4.5.4. 4-Amino-1-((3R,5S)-3,4-dihydroxy-6-(hydroxymethyl)-5-
((3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-
pyran-2-yloxy)tetrahydro-2H-pyran-2-yl)-3-methyl-1H-pyrazol-
5(4H)-one (300b). The product 300b was prepared according to the
general procedure C using the following amounts: 3b (1.00 g,
2.36 mmol) to afford 300b (0.98 g, 96%) as a coloured solid as
see Table 7 in Supplementary data for the glycidic part and
d
¼171.6,
164.3, 149.8, 69.4, 60.6, 14.5 ppm. MS (ESI): m/z¼637.23 [Mþ1]þ.
C18H26Br2N2O13 (635.98): calcd C, 33.87; H, 4.11; N, 4.39; found: C,
33.94; H, 4.11; N, 4.46.
a mixture of
Me2SO):
¼11.50 (s, 1H), 5.11e4.56 (m, 2H, both anomers),
4.31e4.16 (m, 4H, both anomers), 3.88e3.79 (m, 6H, both anomers),
3.44e3.40 (m, 2H, both anomers), 2.70 (s, 3H, CH3ePyr) ppm. 13
NMR (50 MHz, Me2SO): see Table 7 in Supplementary data for the
a- and b
-pyranosic anomers. 1H NMR (200 MHz,
d
4.5. General procedure D: synthesis of the 4-amino pyr-
azolidine-3,5-dione and pyrazolidine-5-dione derivatives
C
To a solution of 3a,b, 4a,b, 5a,b (1 mol) in HCl 1 N/water (1:10)
and cooled to 0 ꢀC in an ice-bath. With stirring, sodium nitrite
(1.2 mol) was added portion wise over 1 h, while maintaining the
internal temperature near 0 ꢀC. After that, the flask was removed
from ice-bath and the resulting mixture was stirred at room tem-
perature. After 3 h, the water was removed under reduced pressure
to yield the oxime derivatives. To a solution of the oxime derivatives
(1 mol) in DMSO (10 mL), ammonium chloride (4 mol) and zinc
dust (2 mol) were added and the resulting mixture was stirred
under reflux. After the completion of the reaction, the reaction
mixture was filtered through Celite. The filtrate was evaporated
under vacuum and the residue was purified by precipitation with
ethanol to yield the corresponding 4-amino-pyrazolidine-3,5-
dione and 4-amino-pyrazolidine-5-dione derivatives.
glycidic part and
d
¼147.4, 140.7, 123.4, 12.6 ppm. MS (ESI):
m/z¼438.32 [Mþ1]þ. C16H27N3O11 (437:17): calcd C, 43.93; H, 6.22;
N, 9.61; found: C, 44.12; H, 6.35; N, 9.73.
4.5.5. Ethyl 4-amino-5-oxo-1-((3R,5S)-3,4,5-trihydroxy-6-(hydrox-
ymethyl)tetrahydro-2H-pyran-2-yl)-4,5-dihydro-1H-pyrazole-3-
carboxylate (400a). The product 400a was prepared according to the
general procedure C using the following amounts: 4a (1.00 g,
3.14 mmol), bromine (0.32 mL, 6.28 mmol) in acetic acid (15 mL) to
afford 400a (0.99 g, 96%) as a coloured solid as a mixture of
-pyranosic anomers. 1H NMR (200 MHz, Me2SO):
a
- and
b
d¼11.49 (s, 1H),
5.28e5.22 (d, 1H), 4.25 (q, J¼7.1 Hz, 2H, CH2), 3.83e3.62 (m, 4H),
3.47e3.30 (m, 2H), 1.30 (t, J¼7.0 Hz, 3H, CH3) ppm. 13C NMR
(50 MHz, Me2SO): see Table 6 in Supplementary data for the gly-
cidic part and
d
¼160.9, 144.3, 136.4, 126.6, 60.9, 14.7 ppm. MS (ESI):
4.5.1. 4-Amino-1-((3R,5S)-3,4,5-trihydroxy-6-(hydroxymethyl)tetra-
hydro-2H-pyran-2-yl)pyrazolidine-3,5-dione (500a). The product
500a was prepared according to the general procedure D using the
following amounts: 5a (1.00 g, 3.80 mmol) to afford 500a (1.00g,
m/z¼334.32 [Mþ1]þ. C12H19N3O8 (333.13): calcd C, 43.24; H, 5.75;
N, 12.61; found: C, 43.32; H, 5.86; N, 12.70.
4.5.6. Ethyl 4-amino-1-((3R,5S)-3,4-dihydroxy-6-(hydroxymethyl)-
5-((3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-
pyran-2-yloxy)tetrahydro-2H-pyran-2-yl)-5-oxo-4,5-dihydro-1H-
pyrazole-3-carboxylate (400b). The product 400b was prepared
according to the general procedure C using the following amounts:
4b (1.00 g, 2.08 mmol) to afford 400b (1.70 g, 97%) as a coloured solid
95%) as a coloured solid as a mixture of
anomers. 1H NMR (200 MHz, Me2SO):
¼5.28e5.22 (d, 1H), 4.52
(s, 1H), 3.82e3.61 (m, 4H), 3.47e3.31 (m, 2H). 13C NMR (50 MHz,
a- and b-pyranosic
d
Me2SO): see Table 5 for the glycidic part and
d
¼170.6, 168.9,
77.5 ppm. MS (ESI): m/z¼278.25 [Mþ1]þ. C9H15N3O7 (277.08):
calcd C, 38.99; H, 5.45; N, 15.16; found: C, 39.21; H, 5.53; N,
15.22.
as a mixture of
Me2SO):
a- and b
-pyranosic anomers. 1H NMR (200 MHz,
d
¼11.52 (s, 1H), 5.10e4.55 (m, 2H, both anomers), 4.24 (q,
J¼6.9 Hz, 2H, CH2), 4.32e4.16 (m, 4H, both anomers), 3.87e3.77 (m,
6H, both anomers), 3.44e3.41 (m, 2H, both anomers), 1.28 (t,
J¼6.9 Hz, 3H, CH3) ppm. 13C NMR (50 MHz, Me2SO): see Table 7 in
4.5.2. 4-Amino-1-((3R,5S)-3,4-dihydroxy-6-(hydroxymethyl)-5-
((3R,4S,5R,6R)-3,4,5-trihydroxy-6-(hydroxymethyl) tetrahydro-2H-
pyran-2-yloxy)tetrahydro-2H-pyran-2-yl)pyrazolidine-3,5-dione
(500b). The product 500b was prepared according to the general
procedure C using the following amounts: 5b (1.00 g, 2.35 mmol)
Supplementary data for the glycidic part and
d¼160.7, 144.5, 136.4,
126.5, 60.7, 14.8 ppm. MS (ESI): m/z¼496.29 [Mþ1]þ. C18H29N3O13
(495.17): calcd C, 43.64; H, 5.90; N, 8.48; found: C, 43.73; H, 5.96; N,
8.54.
to afford 500b (0.99 g, 93%) as a coloured solid as a mixture of
a-
and
b
-pyranosic anomers. 1H NMR (200 MHz, Me2SO):
d
¼5.11e4.55 (m, 2H, both anomers), 4.52 (s, 1H), 4.30e4.15 (m,
4.6. General procedure E: synthesis of the azoic dyes 10aed
and 11a,b
4H, both anomers), 3.88e3.79 (m, 6H, both anomers), 3.45e3.42
(m, 2H, both anomers) ppm. 13C NMR (50 MHz, Me2SO): see
Table 7 in Supplementary data for the glycidic part and
d
¼170.9,
To a solution of 4-amino aniline (1 mol) in 15 mL of water/HCl
1 N 15:1.5, a solution of NaNO2 (2.4 mmol) in water (2 mL) was
added drop wise at 0 Cꢀ and the resulting mixture was stirred for
30 min. The diazonium salt solution previously prepared was added
drop wise to the solution of sugar pyrazolidine-3,5-dione 5a,b
sugar pyrazolidine-5-dione 3a,b, 4a,b derivatives (2 mmol) in water
(3 mL) and the combined solution was maintained at 0 Cꢀ for 6 h
with stirring. After this time the resulting mixture was filtered and
the resulting solution was purified by precipitation with ethanol to
yield the corresponding azo dyes 10aed and 11a,b.
168.4, 76.4 ppm. MS (ESI): m/z¼440.29 [Mþ1]þ. C15H25N3O12
(439.14): calcd C, 41.00; H, 5.74; N, 9.56; found: C, 41.12; H, 5.83;
N, 9.64.
4.5.3. 4-Amino-3-methyl-1-((3R,5S)-3,4,5-trihydroxy-6-(hydrox-
ymethyl)tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5(4H)-one
(300a). The product 300a was prepared according to the general
procedure C using the following amounts: 3a (1.00 g, 2.41 mmol) to
afford 300a (0.97 g, 94%) as a coloured solid as a mixture of
pyranosic anomers. 1H NMR (200 MHz, Me2SO):
a
- and
b-
d
¼11.54 (s, 1H,
OH), 5.29e5.21 (d, 1H), 3.81e3.61 (m, 4H), 3.47e3.30 (m, 2H), 2.71
4.6.1. Synthesis of the dye 10a. The product 10a was prepared
according to the general procedure E using the following amounts:
4-amino aniline (0.50 g, 4.63 mmol), 4a (2.95 g, 9.26 mmol), NaNO2
(0.77 g, 11.11 mmol), in HCl 1 N/water (10 mL), to afford 10a (3.26 g,
(s, 3H, CH3ePyr) ppm. 13C NMR (50 MHz, Me2SO): see Table 6 in
Supplementary data for the glycidic part and
d
¼147.2, 140.4,
123.8, 12.4 ppm. MS (ESI): m/z¼276; 31 [Mþ1]þ. C10H17N3O6

2248
J. Isaad / Tetrahedron 69 (2013) 2239e2250
92%) as a mixture of
a
- and
b
-pyranosic anomers. 1H NMR
both anomers), 3.44e3.41 (m, 4H, both anomers) ppm. 13C NMR
(200 MHz, Me2SO):
d
¼6.42 (m, 4H), 5.28e5.21 (d, 2H), 4.25
(50 MHz, Me2SO): see Table 7 in Supplementary data for the gly-
(q, J¼7.0 Hz, 4H, CH2), 3.82e3.61 (m, 8H), 3.47e3.30 (m, 4H), 1.27
cidic part and
d
¼168.4, 159.4, 136.5, 133.6, 120.4 ppm. MS (ESI): m/
(t, J¼7.0 Hz, 6H, CH3) ppm. 13C NMR (50 MHz, Me2SO): see Table 6 in
z¼978.29 [Mþ1]þ. C36H50N8O24 (979.36): calcd C, 44.17; H, 5.15; N,
Supplementary data for the glycidic part and
d
¼168.9, 164.3, 136.2,
11.45; found: C, 44.22; H, 5.25; N, 11.64.
133.6, 120.6, 60.8, 14.5 ppm. MS (ESI): m/z¼767.37 [Mþ1]þ.
C30H38N8O16 (766.24): calcd C, 47.00; H, 5.00; N, 14.62; found: C,
47.13; H, 5.16; N, 14.73.
4.7. General procedure F: synthesis of the azoic dyes 8aed and
9a,b
4.6.2. Synthesis of the dye 10b. The dye 10a was prepared according
to the general procedure E using the following amounts: 4-amino
aniline (0.50 g, 4.63 mmol), 3a (2.40 g, 9.26 mmol), NaNO2
(0.77 g, 11.11 mmol), in HCl 1 N/water (10 mL), to afford 10b (2.82 g,
To a solution of sugar 4-amino-pyrazolidine-3,5-dione 500a,b or
sugar 4-amino-pyrazolidine-5-dione 300a,b, 400a,b derivatives
(1 mol) in 15 mL of water/HCl 1 N 15:1.5, a solution of NaNO2
(1.2 mol) in water (2 mL) was added drop wise at 0 Cꢀ and the
resulting mixture was stirred for 30 min. The diazonium salt so-
lution previously prepared was added drop wise to the solution of
sugar pyrazolidine-3,5-dione derivatives or sugar pyrazolidine-5-
dione derivatives (1 mmol) in water (3 mL) and the combined so-
lution was maintained at 0 Cꢀ for 6 h with stirring. After this time
the resulting mixture was filtered and the resulting solution was
purified by precipitation with ethanol to yield the corresponding
azo dyes 8aed and 9a,b.
94%) as a mixture of
a- and b
-pyranosic anomers. 1H NMR
(200 MHz, Me2SO):
d
¼6.44 (m, 4H), 5.28e5.20 (d, 2H), 3.82e3.62
(m, 8H), 3.48e3.30 (m, 4H), 2.27 (s, 6H, CH3) ppm. 13C NMR
(50 MHz, Me2SO): see Table 6 in Supplementary data for the gly-
cidic part and
d
¼168.6, 148.3, 133.4, 128.6, 120.5, 13.3 ppm. MS
(ESI): m/z¼651.45 [Mþ1]þ. C26H34N8O12 (650.23): calcd C, 48.00; H,
5.27; N, 17.22; found: C, 48.14; H, 5.34; N, 17.31.
4.6.3. Synthesis of the dye 10c. The product 10c was prepared
according to the general procedure E using the following amounts:
4-amino aniline (0.50 g, 4.63 mmol), 4b (4.45 g, 9.26 mmol), NaNO2
(0.77 g, 11.11 mmol), in HCl 1 N/water (10 mL), to afford 10c (4.49 g,
4.7.1. Synthesis of the dye 8a. The product 8a was prepared
according to the general procedure F using the following amounts:
400a (1.00 g, 2.99 mmol), 4a (0.95 g, 2.99 mmol), NaNO2 (0.24 g,
3.60 mmol), in HCl 1 N/water (10 mL), to afford 8a (1.86 g, 94%). 1H
92%) as a mixture of
(200 MHz, Me2SO):
anomers), 4.31e4.16 (m, 12H, both anomers), 3.88e3.79 (m, 12H,
both anomers), 3.44e3.41 (m, 4H, both anomers), 1.28 (t, J¼7.4 Hz,
6H, CH3) ppm. 13C NMR (50 MHz, Me2SO): see Table 5 for the gly-
a- and b
-pyranosic anomers. 1H NMR
d
¼6.42 (m, 4H), 5.11e4.55 (m, 4H, both
NMR (200 MHz, Me2SO):
d
¼5.28e5.20 (d, 2H), 4.27 (q, J¼7.2 Hz, 4H,
CH2), 3.82e3.61 (m, 9H), 3.47e3.31 (m, 4H), 1.31 (t, J¼7.2 Hz, 6H,
CH3) ppm. 13C NMR (50 MHz, Me2SO): see Table 6 in Supplementary
data for the glycidic part and
d
¼171.2,168.5,163.6,149.6,135.9, 61.4,
cidic part and
d
¼168.7, 164.5, 136.3, 133.6, 120.5, 60.9, 14.8 ppm. MS
60.2, 14.3 ppm. MS (ESI): m/z¼663.35 [Mþ1]þ. C24H34N6O16
(662.21): calcd C, 43.51; H, 5.17; N, 12.68; found: C, 43.58; H, 5.27;
N, 12.75.
(ESI): m/z¼1091.54 [Mþ1]þ. C42H58N8O26 (1090.35): calcd C, 46.24;
H, 5.36; N, 10.27; found: C, 46.33; H, 5.43; N, 10.37.
4.6.4. Synthesis of the dye 10d. The dye 10d was prepared accord-
ing to the general procedure E using the following amounts:
4-amino aniline (0.50 g, 4.63 mmol), 3b (4.44 g, 9.26 mmol), NaNO2
(0.77 g, 11.11 mmol), in HCl 1 N/water (10 mL), to afford 10d (4.77 g,
4.7.2. Synthesis of the dye 8b. The product 8b was prepared
according to the general procedure F using the following amounts:
300a (1.00 g, 3.62 mmol), 3a (0.94 g, 3.62 mmol), NaNO2 (0.28 g,
4.34 mmol), in HCl 1 N/water (10 mL), to afford 8b (1.83 g, 93%). 1H
93%) as a mixture of
(200 MHz, Me2SO):
anomers), 4.32e4.16 (m, 8H, both anomers), 3.87e3.77 (m, 12H,
both anomers), 3.45e3.41 (m, 4H, both anomers), 2.28 (s, 6H,
CH3) ppm. 13C NMR (50 MHz, Me2SO): see Table 7 in Supplementary
a
- and
b
-pyranosic anomers. 1H NMR
NMR (200 MHz, Me2SO):
d
¼5.28e5.21 (d, 2H), 3.82e3.61 (m, 9H),
d
¼6.44 (m, 4H), 5.11e4.54 (m, 4H, both
3.47e3.31 (m, 4H), 2.33 (s, 6H, CH3) ppm. 13C NMR (50 MHz,
Me2SO): see Table 6 in Supplementary data for the glycidic part and
d
¼171.6, 168.7, 155.7, 148.4, 128.6, 66.9, 19.5, 13.4 ppm. MS (ESI): m/
z¼547.34 [Mþ1]þ. C20H30N6O12 (546.19): calcd C, 43.96; H, 5.53; N,
data for the glycidic part and
d
¼168.5, 148.5, 133.4, 128.4, 120.4,
15.38; found: C, 44.08; H, 5.63; N, 15.44.
13.4 ppm. MS (ESI): m/z¼975.53 [Mþ1]þ. C38H54N8O22 (974.34):
calcd C, 46.82; H, 5.58; N, 11.49; found: C, 46.94; H, 5.64; N, 11.53.
4.7.3. Synthesis of the dye 8c. The product 8c was prepared
according to the general procedure F using the following amounts:
400b (1.00 g, 2.01 mmol), 4b (0.95 g, 2.01 mmol), NaNO2 (0.16 g,
2.41 mmol), in HCl 1 N/water (10 mL), to afford 8c (1.83 g, 94%). 1H
4.6.5. Synthesis of the dye 11a. The product 11a was prepared
according to the general procedure E using the following amounts:
4-amino aniline (0.50 g, 4.63 mmol), 5a (2.43 g, 9.26 mmol), NaNO2
(0.77 g, 11.11 mmol), in HCl 1 N/water (10 mL), to afford 11a (2.88 g,
NMR (200 MHz, Me2SO):
d
¼5.10e4.55 (m, 4H, both anomers),
4.31e4.16 (m, 12H, both anomers), 3.88e3.79 (m, 13H, both
anomers), 3.44e3.41 (m, 4H, both anomers), 1.31 (t, J¼6.6 Hz, 6H,
CH3) ppm. 13C NMR (50 MHz, Me2SO): see Table 7 in Supplementary
96%) as a mixture of
(200 MHz, Me2SO):
¼6.55 (m, 4H),
(m, 8H), 3.47e3.30 (m, 4H) ppm. 13C NMR (50 MHz, Me2SO): see
a
- and
b
-pyranosic anomers. 1H NMR
¼5.28e5.21 (d, 2H), 3.82e3.61
d
d
data for the glycidic part and
d
¼171.4, 168.5,163.7, 149.9,135.8, 61.4,
Table 7 in Supplementary data for the glycidic part and
d
¼168.2,
60.2, 14.1 ppm. MS (ESI): m/z¼987.46 [Mþ1]þ. C36H54N6O26
(986.31): calcd C, 43.82; H, 5.52; N, 8.52; found: C, 43.98; H, 5.64; N,
8.66.
159.4, 136.7, 133.1, 120.2 ppm. MS (ESI): m/z¼655.35 [Mþ1]þ.
C24H30N8O14 (654.19): calcd: C, 44.04; H, 4.62; N, 17.12; found: C,
44.17; H, 4.72; N, 17.23.
4.7.4. Synthesis of the dye 8d. The product 8d was prepared
according to the general procedure F using the following amounts:
300b (1.00 g, 2.28 mmol), 3b (0.94 g, 2.28 mmol), NaNO2 (0.17 g,
2.74 mmol), in HCl 1 N/water (10 mL), to afford 8d (1.83 g, 93%). 1H
4.6.6. Synthesis of the dye 11b. The product 11b was prepared
according to the general procedure E using the following amounts:
4-amino aniline (0.50 g, 4.63 mmol), 5b (2.42 g, 9.26 mmol), NaNO2
(0.77 g, 11.11 mmol), in HCl 1 N/water (10 mL), to afford 11a (4.16 g,
NMR (200 MHz, Me2SO):
4.32e4.16 (m, 8H, both anomers), 3.88e3.79 (m, 13H, both anom-
ers), 3.43e3.40 (m, 4H, both anomers), 2.35 (s, 6H, CH3) ppm. 13
NMR (50 MHz, Me2SO): see Table 7 in Supplementary data for the
d
¼5.10e4.54 (m, 4H, both anomers),
92%) as a mixture of
(200 MHz, Me2SO):
¼6.56 (m, 4H), 5.10e4.55 (m, 4H, both
anomers), 4.31e4.16 (m, 8H, both anomers), 3.88e3.79 (m, 12H,
a- and b
-pyranosic anomers. 1H NMR
d
C

J. Isaad / Tetrahedron 69 (2013) 2239e2250
2249
glycidic part and
d
¼171.7, 168.7, 155.5, 148.5, 128.8, 66.8, 19.8,
14b (1.00 g, 1.56 mmol), 4b (0.67 g, 1.56 mmol), NaH (0.04 g,
1.56 mmol) to afford 6a (1.40 g, 94%). 1H NMR (200 MHz, Me2SO):
13.6 ppm. MS (ESI): m/z¼871.48 [Mþ1]þ. C32H50N6O22 (870.30):
calcd C, 44.14; H, 5.79; N, 9.65; found: C, 44.22; H, 5.84; N, 9.75.
d
¼5.10e4.55 (m, 4H, both anomers), 4.31e4.16 (m, 12H, both
anomers), 3.88e3.79 (m, 12H, both anomers), 3.44e3.41 (m, 4H,
both anomers), 1.28 (t, J¼7.0 Hz, 6H, CH3) ppm. 13C NMR (50 MHz,
Me2SO): see Table 7 in Supplementary data for the glycidic part and
4.7.5. Synthesis of the dye 9a. The product 9a was prepared
according to the general procedure F using the following amounts:
500a (1.00 g, 3.59 mmol), 5a (0.95 g, 3.59 mmol), NaNO2 (0.28 g,
4.31 mmol), in HCl 1 N/water (10 mL), to afford 8d (1.88 g, 95%). 1H
d
¼165.5, 1632, 148.7, 137.6, 61.7, 14.0 ppm. MS (ESI): m/z¼957.36
[Mþ1]þ. C36H52N4O26 (956.29): calcd C, 45.19; H, 5.48; N, 5.86;
NMR (200 MHz, Me2SO):
d¼5.28e5.21 (d, 2H), 4.48 (s, 1H),
found: C, 45.25; H, 5.54; N, 5.94.
3.82e3.62 (m, 8H), 3.47e3.31 (m, 4H) ppm. 13C NMR (50 MHz,
Me2SO): see Table 6 in Supplementary data for the glycidic part and
4.8.4. Synthesis of the dye 6d. The product 6d was prepared
according to the general procedure G using the following amounts:
13b (1.00 g, 1.73 mmol), 3b (0.73 g, 1.73 mmol), NaH (0.04 g,
1.73 mmol) to afford 6d (1.18 g, 97%). 1H NMR (200 MHz, Me2SO):
d
¼170.4, 168.6, 168.2, 159.5, 136.7, 83.8 ppm. MS (ESI): m/z¼551.32
[Mþ1]þ. C18H26N6O14 (550.15): calcd C, 39.28; H, 4.76; N, 15.27;
found: C, 39.33; H, 4.84; N, 15.34.
d
¼5.10e4.54 (m, 4H, both anomers), 4.31e4.15 (m, 8H, both
4.7.6. Synthesis of the dye 9b. The product 9b was prepared
according to the general procedure F using the following amounts:
500b (1.00 g, 2.28 mmol), 5b (0.94 g, 2.28 mmol), NaNO2 (0.28 g,
2.74 mmol), in HCl 1 N/water (10 mL), to afford 8d (1.77 g, 95%). 1H
anomers), 3.88e3.78 (m, 12H, both anomers), 3.44e3.41 (m, 4H,
both anomers), 2.30 (s, 6H, CH3) ppm. 13C NMR (50 MHz, Me2SO):
see Table 7 in Supplementary data for the glycidic part and
d
¼165.7,
147.8, 143.6, 13.7 ppm. MS (ESI): m/z¼840.39 [Mþ1]þ. C32H48N4O22
(840.28): calcd C, 45.71; H, 5.75; N, 6.66; found: C, 45.78; H, 5.84; N,
6.76.
NMR (200 MHz, Me2SO):
d
¼5.10e4.55 (m, 4H, both anomers), 4.46
(s, 1H), 4.31e4.16 (m, 8H, both anomers), 3.88e3.78 (m, 12H, both
anomers), 3.44e3.40 (m, 4H, both anomers) ppm. 13C NMR
(50 MHz, Me2SO): see Table 7 in Supplementary data for the gly-
4.8.5. Synthesis of the dye 7a. The product 7a was prepared
according to the general procedure G using the following amounts:
12a (1.00 g, 2.39 mmol), 5a (0.62 g, 2.39 mmol), NaH (0.05 g,
2.39 mmol) to afford 7a (1.26 g, 95%). 1H NMR (200 MHz, Me2SO):
cidic part and
d
¼170.5,168.6,168.1,159.6,136.8, 83.7 ppm. MS (ESI):
m/z¼875.37 [Mþ1]þ. C30H46N6O24 (874.26): calcd C, 41.19; H, 5.30;
N, 9.61; found: C, 41.26; H, 5.38; N, 9.72.
d
¼5.28e5.21 (d, 1H), 3.82e3.61 (m, 4H), 3.47e3.30 (m, 2H), ppm.
4.8. General procedure G: synthesis of the H-chromophore
13C NMR (50 MHz, Me2SO): see Table 6 in Supplementary data for
dyes 6aed and 7a,b
the glycidic part and
d
¼163.9, 163.1, 149.3 ppm. MS (ESI):
m/z¼521.31 [Mþ1]þ. C18H24N4O14 (520.13): calcd C, 41.54; H, 4.65;
To a solution of sugar pyrazolidine-3,5-dione 5a,b or sugar
pyrazolidine-5-one derivatives 3a,b, 4a,b (1 mol) in DMSO (15 mL),
a solution of NaH (2 mol) in THF (2 mL) was added drop wise at 0 Cꢀ
and the resulting mixture was stirred for 30 min sugar 4,4-
dibromo-pyrazolidine-3,5-dione 12aed or sugar 4,4-dibromo-
pyrazolidine-5-one 13aed, 14aed derivatives (1 mmol) was dis-
solved in DMSO (3 mL) and added to the first solution and the
resulting mixture was stirred at room temperature for 12 h. After
this time, the resulting mixture was filtered and the resulting so-
lution was purified by precipitation with ethanol to yield the cor-
responding H-chromophore dyes 6aed and 7a,b.
N, 10.77; found: C, 41.63; H, 4.73; N, 10.83.
4.8.6. Synthesis of the dye 7b. The product 7b was prepared
according to the general procedure G using the following amounts:
12b (1.00 g, 1.72 mmol), 5b (0.73 g, 1.72 mmol), NaH (0.04 g,
1.72 mmol) to afford 7a (1.26 g, 95%). 1H NMR (200 MHz, Me2SO):
d
¼5.10e4.55 (m, 2H, both anomers), 4.31e4.16 (m, 4H, both
anomers), 3.88e3.79 (m, 6H, both anomers), 3.44e3.41 (m, 2H,
both anomers) ppm. 13C NMR (50 MHz, Me2SO): see Table 7 in
Supplementary data for the glycidic part and
d
¼163.7, 163.3,
149.3 ppm. MS (ESI): m/z¼845.41 [Mþ1]þ. C30H44N4O24 (844.23):
calcd C, 42.66; H, 5.25; N, 6.63; found: C, 42.74; H, 5.32; N, 6.70.
4.8.1. Synthesis of the dye 6a. The product 6a was prepared
according to the general procedure G using the following amounts:
14a (1.00 g, 2.10 mmol), 4a (0.67 g, 2.10 mmol), NaH (0.06 g,
2.10 mmol) to afford 6a (1.26 g, 95%). 1H NMR (200 MHz, Me2SO):
4.8.7. Synthesis of dye 15a. The product 15a was prepared
according to the general procedure G. 1H NMR (200 MHz, Me2SO):
4.24 (q, J¼7.2 Hz, 4H, CH2), 1.30 (t, J¼7.2 Hz, 6H, CH3) ppm. 13C NMR
d
¼5.29e5.21 (d, 2H), 4.24 (q, J¼7.2 Hz, 4H, CH2), 3.82e3.61 (m, 8H),
(50 MHz, Me2SO):
d
¼174.5, 163.6, 143.7, 137.6, 61.4, 14.2 ppm. MS
3.47e3.30 (m, 4H), 1.30 (t, J¼7.2 Hz, 6H, CH3) ppm. 13C NMR
(ESI): m/z¼309.22 [Mþ1]þ. C12H12N4O6 (308.08): calcd C, 46.76; H,
(50 MHz, Me2SO): see Table 6 in Supplementary data for the gly-
3.92; N, 18.18; found: C, 46.83; H, 4.12; N, 18.23.
cidic part and
d
¼165.4, 163.2, 143.9, 137.3, 61.8, 14.1 ppm. MS (ESI):
m/z¼633.29 [Mþ1]þ. C24H32N4O16 (632.18): calcd C, 45.57; H, 5.10;
4.8.8. Synthesis of dye 15b. The product 15b was prepared
N, 8.86; found: C, 45.63; H, 5.17; N, 8.94.
according to the general procedure G. 1H NMR (200 MHz, Me2SO):
2.34 (s, eH, CH3) ppm. 13C NMR (50 MHz, Me2SO):
d
¼174.3, 147.8,
4.8.2. Synthesis of the dye 6b. The product 6b was prepared
according to the general procedure G using the following amounts:
13a (1.00 g, 2.40 mmol), 3a (0.67 g, 2.40 mmol), NaH (0.06 g,
2.40 mmol) to afford 6b (1.18 g, 97%). 1H NMR (200 MHz, Me2SO):
143.6, 13.8 ppm. MS (ESI): m/z¼337.22 [Mþ1]þ. C8H8N4O2 (192.06):
calcd C, 50.00; H, 4.20; N, 29.15; found: C, 50.11; H, 4.28; N, 29.23.
4.8.9. Synthesis of dye 16. The product 16 was prepared according
to the general procedure G. 1H NMR (200 MHz, Me2SO): 2.34 (s, eH,
d
¼5.29e5.21 (d, 2H), 3.82e3.61 (m, 8H), 3.47e3.30 (m, 4H), 2.32 (s,
6H, CH3) ppm. 13C NMR (50 MHz, Me2SO): see Table 6 in
CH3) ppm. 13C NMR (50 MHz, Me2SO):
d
¼163.5, 149.5 ppm. MS
Supplementary data for the glycidic part and
d
¼165.6, 147.7,
(ESI): m/z¼197.19 [Mþ1]þ. C6H4N4O4 (196.02): calcd C, 36.74; H,
143.4, 13.8 ppm. MS (ESI): m/z¼517.31 [Mþ1]þ. C20H28N4O12
(516.18): calcd C, 46.51; H, 5.46; N, 10.85; found: C, 46.58; H, 5.52;
N, 10.94.
2.06; N, 28.57; found: C, 36.82; H, 2.11; N, 28.62.
4.9. Synthesis of dye 17a
4.8.3. Synthesis of the dye 6c. The product 6c was prepared
according to the general procedure G using the following amounts:
The product 17a was prepared according to the general pro-
cedure F. 1H NMR (200 MHz, Me2SO): 4.45 (s, 1H), 4.25 (q, J¼6.9 Hz,

2250
J. Isaad / Tetrahedron 69 (2013) 2239e2250
4H, CH2), 1.30 (t, J¼6.9 Hz, 6H, CH3) ppm. 13C NMR (50 MHz,
(50 MHz, Me2SO):
d
¼168.9, 136.6, 133.3, 120.6 ppm. MS (ESI): m/
Me2SO):
d
¼173.3, 163.3, 161.2, 149.4, 136.5, 136.7, 62.8, 61.4,
z¼331.27 [Mþ1]þ. C12H10N8O4 (330.08): calcd C, 43.64; H, 3.05; N,
14.1 ppm. MS (ESI): m/z¼339.28 [Mþ1]þ. C12H14N6O6 (338.10):
33.93; found: C, 43.77; H, 3.17; N, 34.11.
calcd C, 42.61; H, 4.17; N, 24.84; found: C, 42.75; H, 4.22; N, 24.94.
Acknowledgements
4.10. Synthesis of dye 17b
ThisworkisfinanciallysupportedbyGEMTEXLaboratorydFrance.
We thank Mr. Christian Catel (technician of GEMTEX laboratory) for
his kind disponibility.
The product 17b was prepared according to the general pro-
cedure F. 1H NMR (200 MHz, Me2SO): 4.46 (s, 1H), 2.33 (s, 6H,
CH3) ppm. 13C NMR (50 MHz, Me2SO):
d
¼173.4, 161.5, 155.3, 148.8,
128.5, 69.8, 14.2 ppm. MS (ESI): m/z¼223.26 [Mþ1]þ. C8H10N6O2
(222.09): calcd C, 43.24; H, 4.54; N, 37.82; found: C, 43.33; H, 4.62;
N, 37.93.
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2013.01.038.
4.11. Synthesis of dye 18
References and notes
The product 18 was prepared according to the general procedure
F. 1H NMR (200 MHz, Me2SO): 4.49 (s, 1H) ppm. 13C NMR (50 MHz,
1. The Chemistry of Heterocyclic Compounds, Volume 30, Special Topics in Hetero-
cyclic Chemistry; Weissberger, A., Wiley, R. H., Wiley, P., Eds.; John Wiley:
New York, NY, 1964.
2. Hiremith, S. P.; Rudresh, K.; Saundan, A. R. I. Indian J. Chem. 2002, 41, 394.
3. Joerg, S.; Reinhold, G.; Otto, S.; Joachim, S. H.; Robert, S.; Klaus, L. Ger Offen.
1988; 3, p 625.
Me2SO):
d
¼170.4, 168.4, 136.3, 85.1 ppm. MS (ESI): m/z¼227.22
[Mþ1]þ. C6H6N6O4 (226.05): calcd C, 31.87; H, 2.67; N, 37.16; found:
C, 31.95; H, 2.76; N, 37.25.
4. Dhol, P. N.; Achary, T. E.; Nayak, A. J. Indian Chem. Soc. 1975, 2, 1196.
5. Souza, F. R.; Souaza, V. T.; Ratzlaff, V.; Borges, L. P.; Olivera, M. R.; Bonacorso, H.
G. Eur. J. Pharmacol. 2002, 451, 141.
4.12. Synthesis of dye 19a
6. Singh, J.; Tripathy, R. PCT Int Appl, 2001, number 138.
7. Miyara, H. Bull. Chem. Soc. Jpn. 1963, 36, 382.
The product 19a was prepared according to the general pro-
cedure E. 1H NMR (200 MHz, Me2SO): 6.91 (m, 4H), 4.26 (q,
J¼6.6 Hz, 4H, CH2), 1.28 (t, J¼6.6 Hz, 6H, CH3) ppm. 13C NMR
8. Khalifa, H.; Issa, R. M. Egypt. J. Chem. 1974, 17, 581.
9. Azarifar, D.; Shaebanzadeh, M. Molecules 2002, 7, 885.
10. Ali, Kh. K.; Hassan, M. A.; Mohamed, M. M.; El-Sayed, A. M. Dyes Pigments 2005,
66, 241.
11. Isaad, J.; Perwuelz, A. Tetrahedron Lett. 2010, 51, 5328.
12. Isaad, J.; El Achari, A.; Malek, F. Dyes Pigments 2012, 92, 1212.
13. Bianchini, R.; Rolla, M.; Isaad, J.; Guazzelli, L.; Corsi, M.; Bonanni, M. Carbohydr.
Res. 2012, 356, 104.
(50 MHz, Me2SO):
d
¼163.6, 161.1, 136.1, 133.7, 120.6, 60.9, 13.8 ppm.
MS (ESI): m/z¼443.28 [Mþ1]þ. C18H18N8O6 (442.13): calcd C, 48.87;
H, 4.10; N, 25.33; found: C, 48.94; H, 4.21; N, 25.43.
4.13. Synthesis of dye 19b
14. Bianchini, R.; Catelani, G.; Cecconi, R.; D’Andrea, F.; Guazzelli, L.; Isaad, J.; Rolla,
M. Eur. J. Org. Chem. 2008, 3, 444.
15. Bianchini, R.; Catelani, G.; Cecconi, R.; D’Andrea, F.; Frino, E.; Isaad, J.; Rolla, M.
Carbohydr. Res. 2008, 343, 2067.
The product 19b was prepared according to the general pro-
cedure E. 1H NMR (200 MHz, Me2SO): 6.90 (m, 4H), 2.29 (s, 6H,
16. Isaad, J.; Rolla, M.; Bianchini, R. Eur. J. Org. Chem. 2009, 2748.
CH3) ppm. 13C NMR (50 MHz, Me2SO):
d
¼161.4, 148.4, 133.6, 128.7,
17. Bianchini, R.; Catelani, G.; Frino, E.; Isaad, J.; Rolla, M. BioResources 2007, 2, 630.
120.3, 13.2 ppm. MS (ESI): m/z¼327.31 [Mþ1]þ. C14H14N8O2
(326.12): calcd C, 51.53; H, 4.32; N, 34.34; found: C, 51.63; H, 4.42;
N, 34.47.
€
18. Isaad, J.; Salaun, F. Sens. Actuators, B: Chem. 2011, 157, 26.
19. Isaad, J.; Perwuelz, A. Tetrahedron Lett. 2010, 51, 5810.
20. Isaad, J.; El Achari, A. Anal. Chim. Acta 2011, 694, 120.
21. Isaad, J.; El Achari, A. Tetrahedron 2011, 67, 4196.
22. Isaad, J.; El Achari, A. Tetrahedron 2011, 67, 5678.
23. Kett, W. C.; Batley, M.; Redmond, J. W. Carbohydr. Res. 1997, 299, 129.
24. Williams, J. M. Carbohydr. Res. 1983, 117, 89.
4.14. Synthesis of dye 20
25. Saeed, M.; Williams, J. Carbohydr. Res. 1980, 84, 83.
26. Klessinger, M. Dyes Pigments 1982, 3, 211.
27. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.
The product 20 was prepared according to the general pro-
cedure E. 1H NMR (200 MHz, Me2SO): 6.88 (m, 4H) ppm. 13C NMR