Naturalised dyes: A simple straightforward synthetic route to a new class of dyes - Glycoazodyes (GADs)

Article abstract of DOI:10.1002/ejoc.200600686

We report a process to naturalise synthetic azodyes through their linkage with lactose, or its monosaccharide components, either galactose or glucose, to enhance their solubility, as many other natural dyes. This modification allows the dyeing process of

Full text of DOI:10.1002/ejoc.200600686

FULL PAPER
DOI: 10.1002/ejoc.200600686
Naturalised Dyes: A Simple Straightforward Synthetic Route to a New Class
of Dyes – Glycoazodyes (GADs)
Giuditta Bartalucci,[a] Roberto Bianchini,*[a] Giorgio Catelani,[b] Felicia D’Andrea,[b] and
Lorenzo Guazzelli[b]
Keywords: Azodyes / Carbohydrates / Succinates / Conjugation / Textile dyes
We report a process to naturalise synthetic azodyes through
their linkage with lactose, or its monosaccharide compo-
nents, either galactose or glucose, to enhance their solubility,
as many other natural dyes. This modification allows the dye-
ing process of textile materials to take place in water without
the addition of surfactants or other additives. The synthesis
of the first generation of glycoazodyes (GADs) is carried out
with the use of a diester linker to bond the azodye and the
sugar. Preliminary tinctorial tests showed that this first gener-
ation of GADs is soluble in water and that these new dyes
are multipurpose and are able to dye different fabrics well.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
lutants present in the water have different physical and
chemical properties all that is normally done is to destroy
the chromophores by oxidative treatment of the contami-
nated waters (ozone, H2O2, UV), which removes only the
visible pollution.[4–6] These treatments are efficient for the
depletion of the colour, but the yield of these is variable
and the final oxidation products[7] are often unknown.
Most importantly the colourless oxidation products are
possibly even more dangerous than the starting dyes.[8] For
example, the major disadvantage of using ozone is that it
could form toxic byproducts even from biodegradable sub-
stances.[6,9] A biological approach is also difficult because
of the large variety of species present. Therefore, increasing
attention has been devoted to natural dyes, with the aim
of finding environmentally friendly materials. Natural dyes
extracted from plants or animals do not cover all the mar-
ket requirements, and their isolation from natural sources
is difficult. Furthermore, the impact on the environment is
far from negligible when high quantities are required. These
factors, together with the cost of these processes, have
slowed their development.
In order to devise a new strategy to solve these problems,
we turned to naturalisation of synthetics dyes, through link-
age with a sugar. The aims are: (1) preparation of multipur-
pose dyes able to dye different fabrics (synthetic, natural,
artificial); (2) achievement of hydrophilicity of dyes through
their glycoconjugation, so that dying processes with dis-
perse dyes could be driven without surfactants, that are very
difficult to treat; (3) attainment of easier dying processes
avoiding high temperatures and high pressures; (4) in-
creased affinity towards the textile, improving efficacy, re-
ducing waste; (5) possibility of efficient and more selective
waste treatment, with the use of, for instance, live micro-
organisms to attack the sugar moiety and consequently the
Introduction
Ten thousand different dyes are currently used in the tex-
tile industry, totalling 7ϫ105 tons/year.[1] These dyes fall
into a number of chemical families of which azodyes consti-
tute the largest and most important commercial class. These
molecules contain one, two or three azo groups bound to
benzene, naphthalene or heteroaromatic rings (mono-, di-
or triazodyes, respectively). Other important classes are an-
thraquinonic dyes and indigoids.[2] Dyes are generally ap-
plied in an aqueous solution and require auxiliary chemi-
cals to improve the dyeing process, for example surfactants
to increase solubility, mordants to enhance the fastness of
the dye on the fibre and salts to adjust the pH. Effluent
from textile industries therefore contains a broad spectrum
of contaminants such as highly hydrophobic dyes, sus-
pended solids, chlorinated organic solvents, surfactants,
mordants, metals, etc.[3] Reactive dyes are another class of
environmentally dangerous textile dyes; as the name sug-
gests they are very reactive molecules that form covalent
bond with fibres, but also react with water leading to in-
herent losses. In addition, these molecules can degrade to
aromatic amines, which further damage the environment.[1]
Selective treatment of effluent is not possible because the
type and extent of contamination varies depending on the
fabric dyed or the class of dye used. Because most pol-
[a] Dipartimento di Chimica Organica “Ugo Schiff”, Università di
Firenze,
Via della Lastruccia 13, 50019 Sesto Fiorentino (FI), Italy
Fax: +39-0554577131
E-mail: roberto.bianchini@unifi.it
[b] Dipartimento di Chimica Bioorganica e Biofarmacia, Uni-
versità di Pisa,
Via Bonanno, 33–56126, Pisa, Italy
Fax: +39-0502219660
588
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 588–595

A New Class of Dyes – Glycoazodyes (GADs)
FULL PAPER
covalently bonded chromophoric part, or the use of en-
A key point of this research is the influence of the struc-
zymes able to destroy dyes; (6) use of carbohydrates largely ture of the glycide moiety on the tinctorial properties of
and cheaply available such as -glucose, -galactose and the target GADs. For this purpose, five different protected
lactose; normally discarded in huge quantities in the envi- glycides (1a–e, Scheme 1) have been selected in order to pre-
ronment with an impact that is not negligible.
pare a collection of final modified dyes 5, characterised by
Glycosylation is a general topic in natural compounds, a significant variation on the glycide structure. The planned
other glycoconjugates known are: glycolipids, glycopep- structural differences are: (1) the succinyl–azodye linking
tides, lipopolysaccharides, glycoproteins (also proteogly- position (3-O--glucose versus 6-O--glucose), (2) the gly-
cans).[10] Carminic acid is a red glycosylated dye that occurs cide stereochemistry (6-O--glucose versus 6-O--galac-
naturally in the cochineal insect and it is highly hydrophilic; tose), (3) the glycide size (monosaccharides versus disaccha-
the most important characteristic that we propose to trans- rides).
fer to synthetic dyes.
Conjugation of azodyes with carbohydrates has been, to
the best of our knowledge, reported only in two cases. In
the first report,[11] it was used for developing a methodology
for the identification of the linking point of disaccharides,
whereas in the second report,[12] glycoconjugation was pro-
posed for the enhancement of the hydrophilicity of textile
dyes, but the use of a low-yielding glycosylation reaction
appears hardly applicable to industrial developments.
Results
Here we present the synthesis of a new class of natural-
ised, multipurpose, glycoconjugated dyes,[13] which consist
of a synthetic dye linked to a saccharide from natural and
renewable sources, such as lactose, -glucose or -galactose,
through a bifunctional linker. We decided to modify azod-
yes on their side chain in order to avoid changes in the
chromophoric group so that their original colour was main-
tained. The choice of difunctional linkers to be used for the
linkage of glycide and dye was devised on the basis of their
easy availability and the simplicity of the practical pro-
cedure with the final aim of an industrial development of
the new glycoazodyes (GADs). The succinyl bridge, pre-
viously proposed as a linker between glycosyl donors and
acceptors in intramolecular aglycon delivery (IAD) glycosy-
lations,[14] meets our requirements and has been selected for
the synthesis of the first generation of GADs. Figure 1
shows the two complementary approaches: path a begins by
attaching the linker to a protected glycide, whereas path b
starts in reverse. The resulting structures are diesters, with
the formation of esteric bonds between the sugar and the
succinyl bridge and, on the other side, between the succinyl
bridge and the hydroxy group on the side chain of the azo-
dye.
Scheme 1. Monosuccinates of protected glycides.
Isopropylidene protection was chosen because of the
ready availability of starting materials 1a–e (see Experimen-
tal Section and Scheme 2 for 1b) and the very mild depro-
tection conditions that should not affect the ester functions
of the succinyl bridge. Monosaccharide semisuccinates 2a–
c (Scheme 1) were prepared in good yields (72–96% yield)
by treatment of pertinent acetonides 1a–c with succinic an-
hydride (1.2 equiv.) in toluene, in the presence of triethyl-
amine (TEA) (1 equiv.) and 4-dimethylaminopyridine
(DMAP) (0.1 equiv.). Fully protected lactose semisuccinate
Scheme 2. Preparation of 1,2:3,5-di-O-isopropylidene--glucofur-
anose.
Figure 1. Schematic approaches to glycoazodyes (GADs).
Eur. J. Org. Chem. 2007, 588–595
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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589

G. Bartalucci, R. Bianchini, G. Catelani, F. D’Andrea, L. Guazzelli
FULL PAPER
2e was conveniently prepared from lactose in three steps: tected GADs was made by comparison of their NMR spec-
the first step was the acetonation of lactose,[15] subsequently troscopic data (Tables 1, 2, 3 and 4) with those reported in
the regioselective succinylation of the primary OH-6Ј group the literature for fully deprotected anomers.[18]
of triacetonlactose dimethyl acetal (1d) (76% yield), and fi-
nally the routine acetylation of semisuccinate 2d (Ac2O/Py,
91% yield). Alternatively, 1e (90% yield) was obtained from
acetylation of the secondary 2Ј-OH group from 1d through
a two step reaction,[16] and afterwards 2e was directly pre-
pared by succinylation of 1e.
An alternative approach to the synthesis of GADs starts
with the succinylation of an alcoholic azodye (Figure 1,
path b) that was performed in high yields (90–98% yield)
on commercially available red azodyes 3b (Disperse Red 1)
and 3c (Disperse Red 13), and yellow azodye 3a, prepared
according to a literature method (Scheme 3).[17]
Scheme 4. Protected and deprotected GADs.
UV/Vis absorption spectra of the deprotected GADs pre-
sented slightly different absorptions when made in different
solvents, such as methanol and acetone. In the experimental
Section the UV/Vis absorption spectra of the industrial dye
are also reported, to show the small hypsochromic shift that
results from glycoconjugation.
We carried out preliminary tinctorial studies,[19] which
showed that this first generation of GADs is soluble in
water, as expected, and also that these dyes are multipur-
pose because they dye all of the fabrics we submitted to our
Scheme 3. Azodyes monosuccinates.
The linkage of semisuccinate sugars (2) with appropriate
alcoholic dye 3 to give significant examples of protected
GADs (6a,b,d,e,g and h) was performed in good to excellent
attempts: wool, silk, nylon, polyester and polyurethane;
Table 2. 13C NMR spectroscopic data (δ, ppm) in CDCl3 of the
yields by condensation with a slight excess of NЈ-(3-dimeth-
glycide portion for protected 3-O--glucoyl (2a, 6a and 6b), 6-O-
ylaminopropyl)-N-ethylcarbodiimide hydrochloride in THF
in the presence of a catalytic amount of DMAP. The alter-
native route starting from semisuccinate dyes 4 with selected
alcoholic protected sugars 1 gave comparable results both
in terms of yields and practical procedure to give 6b,c
and f.
The final deprotection step was performed through treat-
ment with 90% aqueous trifluoroacetic acid leading to the
almost quantitative formation of dyes 5a–e (Scheme 4). -
Glucose (5a and 5b), 2Ј-O-acetyl-lactose (5e) and -galac-
tose (5c and 5d) derivatives were isolated as mixtures of the
two pyranose anomers; in the case of 5c and 5d further
amounts of the α-furanose form were also found (about
-glucoyl (2b, 6c and 6d), and 6-O--galactoyl (2c, 6e, 6f and 6g)
derivatives.
Com-
pound
C-1
C-2
C-3
C-4
C-5
C-6
2a
6a
6b
2b
6c
6d
2c
6e
6f
105.0
104.8
104.9
106.2
106.3
106.2
95.7
96.0
96.2
96.0
83.1
83.1
83.1
83.7
83.8
83.7
76.4
76.3
76.4
74.8
74.9
74.8
79.6
79.5
79.5
79.2
79.3
79.2
72.3
72.3
72.5
69.9
70.0
69.9
67.2
67.6
67.1
64.5
64.7
64.6
63.2
63.5
63.7
63.6
70.5[a] 70.1[a] 69.8[a] 65.4
70.8[a] 70.4[a] 70.2[a] 65.7
70.9[a] 70.6[a] 70.3[a] 65.4
70.8[a] 70.4[a] 70.2[a] 65.7
6g
10%). The identification of the isomeric forms of the depro- [a] Assignments may have to be interchanged.
1
Table 1. H NMR spectroscopic data (δ, ppm; J, Hz) in CDCl3 of the glycide portion for protected 3-O--glucoyl (2a, 6a and 6b), 6-O-
-glucoyl (2b, 6c and 6d), and 6-O--galactoyl (2c, 6e, 6f and 6g) derivatives.
Com-
pound
1-H
2-H
3-H
4-H
5-H
6a-H
6b-H
J1,2
J2,3
J3,4
J4,5
J5,6a
J5,6b
J6a,6b
2a
6a
6b
2b
6c
6d
2c
6e
6f
5.87
5.86
5.88
6.00
6.00
6.00
5.54
5.52
5.53
5.53
4.50
4.50
4.51
4.58
4.58
4.58
4.34
4.31
4.33
4.33
5.26
5.25
5.26
4.23
4.23
4.23
4.63
4.50
4.62
4.63
4.21
4.19
4.21
4.33
4.36
4.31
4.30
4.22
4.23
4.23
4.10
4.19
4.05
3.77
3.79
3.79
4.01
4.01
4.03
4.02
4.10
4.10
4.05
4.18
4.17
4.17
4.18
4.22
4.27
4.30
4.10
4.10
4.05
4.34
4.34
4.31
4.21
4.22
4.31
4.30
3.7
3.7
3.7
3.7
3.7
3.7
5.0
4.9
5.0
5.0
0
0
0
0
0
0
2.5
2.4
2.5
2.5
2.2
2.7
2.5
3.8
3.8
3.4
7.9
7.7
7.9
7.9
1.7
n.d.
2.0
7.2
7.0
7.1
1.8
n.d.
1.9
1.9
n.d.
n.d.
n.d.
6.9
7.0
7.1
7.4
n.d.
7.1
n.d.
n.d.
n.d.
3.5
3.4
3.3
4.8
n.d.
5.1
n.d.
n.d.
n.d.
11.8
11.8
11.8
10.2
n.d.
10.9
n.d.
6g
6.9
5.1
590
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Eur. J. Org. Chem. 2007, 588–595

A New Class of Dyes – Glycoazodyes (GADs)
FULL PAPER
Table 3. 13C NMR spectroscopic data (δ, ppm) in Me2SO of the
glycide portion for deprotected 3-O--glucoyl (5a), 6-O--glucoyl
(5b) and 6-O--galactoyl derivatives (5c and 5d).
Our tests have been carried out in standard conditions
and they will be the subject of a dedicated report. Finally,
fastness is very good, and in the case of polyester, excellent.
These initial results have encouraged us to pursue the field
of preparation of GADs, and to consider different types of
linkers and classes of dyes, such as anthraquinonics.
Com-
pound
C-1
C-2
C-3
C-4
C-5
C-6
5b-αp
5a-αp
5b-βp
5a-βp
5c-βf
5d-βf
5c-αp
5d-αp
5c-βp
5d-βp
92.8
92.2
97.3
96.8
101.8
101.8
92.7
92.6
97.4
97.3
72.6
71.9
75.2
76.2
81.3
81.5
68.5
68.6
71.8
71.8
73.4
71.9
76.8
78.6
75.9
76.0
69.1
69.0
71.8
71.8
70.9
70.3
70.6
70.3
82.6
82.5
69.3
69.2
68.7
68.6
69.6
68.1
73.9
78.6
67.2
73.0
67.6
67.5
73.1
73.0
64.8
61.6
64.8
61.6
65.2
65.8
64.6
64.3
64.5
64.3
Experimental Section
General: Melting points were determined with a Kofler hot-stage
apparatus and are uncorrected. Optical rotations were measured
with a Perkin–Elmer 241 polarimeter at 20Ϯ2 °C. 1H NMR and
13C NMR spectra were recorded with a Bruker AC 200, Varian
Gemini instruments at 200 (1H) and 50 (13C) MHz or with a Varian
INOVA600 spectrometer, in the appropriate solvent (internal stan-
dard Me4Si). Assignments were made, when possible, with the aid
of DEPT experiments, for comparison with values for known com-
pounds and applying the known additivity rules,[20] and, in the case
of anomeric mixtures, referring to the differences in the peak inten-
sities. All reactions were followed by TLC on Kieselgel 60 F254 with
detection by UV light and/or with ethanolic 10% phosphomolybdic
or sulfuric acid, and heating. Kieselgel 60 (E. Merck, 70–230 and
230–400 mesh, respectively) was used for column and flash
chromatography. Solvents were dried by distillation according to
standard procedures[21] and stored over 4 Å molecular sieves that
were activated for at least 24 h at 400 °C. Red azodyes 2b (Disperse
Red 1) and 2c (Disperse Red 13) are commercially available
(Sigma–Aldrich), yellow dye 2a was prepared according to the lit-
erature.[17] 1,2:5,6-di-O-isopropylidene-α--glucofuranose (1a) and
1,2:3,4-di-O-isopropylidene-α--galactopyranose (1c) are commer-
cially available (Fluka). Literature methods were used to prepare
2,3:5,6:3Ј,4Ј-tri-O-isopropylidenelactose dimethyl acetal (1d)[15] and
its 2Ј-O-acetate 1e.[16] The known 1,2:3,5-di-O-isopropylidene-α--
glucofuranose[22] (1b) was prepared by the procedure reported be-
low, starting from known 1,2-O-isopropylidene-6-O-pivaloyl--glu-
cofuranose (7).[23]
only cotton dyed poorly. The multipurpose nature of the
industrial dyes is one of their most important properties
because this would allow mixed fabrics, which are very com-
mon on the market, to be dyed. The results of one of these
tests are reported in Figure 2. These tests were performed
in water without the addition of surfactants, under mild
conditions of temperature and pressure. To the best of our
knowledge, disperse dyes, as our starting azodyes, do not
effectively dye wool, and they dye polyester only under
drastic conditions.
1,2:3,5-Di-O-isopropylidene-α-D-glucofuranose (1b): To a solution
of 7[23] (14.0 g, 46.0 mmol) in DMP (350 mL) was added at room
temperature TsOH (400 mg, 2.23 mmol). After 2 h stirring, the re-
action mixture was neutralized with an excess of Et3N (1.5 mL)
and then coevaporated with toluene (5ϫ50 mL) at reduced pres-
sure. The resulting residue was diluted with H2O (30 mL) and ex-
tracted with CH2Cl2 (3ϫ50 mL). The organic phase was dried with
MgSO4 and concentrated at reduced pressure. Purification of the
residue by flash chromatography (hexane/EtOAc, 9:1) afforded
1,2:3,5-di-O-isopropylidene-6-O-pivaloyl-D-glucofuranose (8) (14.5 g,
92%) as an oil. Rf = 0.54 (hexane/EtOAc, 7:3). [α]D = +35.7 (c 1.0,
CHCl3). H NMR (200 MHz, CDCl3): δ = 6.00 (d, J1,2 = 3.7 Hz,
Figure 2. Tinctorial tests on 5d performed on: 1) polyester, 2) cot-
ton, 3) polyester \ polyurethane dyed as polyester, 4) polyester \
polyurethane dyed as wool, 5) wool, 6) cotton \ nylon.
1
1 H, 1-H), 4.58 (d, 1 H, 2-H), 4.31 (dd, J5,6b = 3.6 Hz, J6a,6b
=
Table 4. 13C NMR spectroscopic data (δ, ppm) of the glycide portion for protected and deprotected lactose derivatives.
Compound
Solvent
C-1Ј
C-2Ј
C-3Ј
C-4Ј
C-5Ј
C-6Ј
C-1
C-2
C-3
C-4
C-5
C-6
2d
CD3CN
CD3CN
CDCl3
D2O
CD3OD
D2O
104.1
100.8
100.1
103.7
104.1
103.6
103.8
74.6
73.8
72.5
72.0
71.9
72.0
71.5
80.0
76.7
77.1
73.5
74.0
73.5
74.0
77.7
75.9
73.4
69.5
68.9
69.5
68.2
71.6
71.4
70.6
76.2
75.2
76.2
75.1
64.1
63.9
63.4
62.0
62.0
62.0
62.0
106.4
106.2
104.9
96.6
96.7
92.7
77.8
77.8
75.1
74.8
75.5
72.2
72.3
77.9
78.1
77.9
75.3
75.1
72.4
73.5
74.3
74.6
73.8
79.2
80.5
79.3
81.1
78.6
78.7
78.1
75.6
74.8
71.0
70.3
66.1
65.5
64.6
61.1
60.7
61.0
60.3
2e
6h
β-lactose[a]
β-5e
α-lactose[a]
α-5e
CD3OD
92.4
[a] Taken from ref.[18]
Eur. J. Org. Chem. 2007, 588–595
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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591

G. Bartalucci, R. Bianchini, G. Catelani, F. D’Andrea, L. Guazzelli
FULL PAPER
11.5 Hz, 1 H, 6b-H), 4.30 (dd, J3,4 = 4.0 Hz, J4,5 = 7.1 Hz, 1 H, 4- 4-O-[6-O-(3-Carboxypropanoyl)-3,4-O-isopropylidene-β-
D-galacto-
H), 4.21 (d, 1 H, 3-H), 4.15 (dd, J5,6a = 7.7 Hz, 1 H, 6a-H), 3.78
pyranosyl]-2,3:5,6-di-O-isopropylidene-aldehydo-
D-glucose Dimethyl
(ddd, H, 5-H), 1.49, 1.36 [2s, each 3 H, C(CH3)2], 1.34 [s, 6 H, Acetal (2d): The succinylation of 1d[15] (3.53 g, 6.94 mmol) accord-
C(CH3)2], 1.21 [s, 9 H, (CH3)3C] ppm. 13C NMR (50 MHz, ing to the general procedure, was, in this case, prolonged for 24 h,
CDCl3): δ = 177.9 (CO), 112.0, 100.8 [2ϫC(CH3)2], 106.3 (C-1), and afforded, after flash chromatographic purification (hexane/
83.7 (C-2), 79.3 (C-4), 74.8 (C-3), 70.2 (C-5), 63.9 (C-6), 38.6 EtOAc, 3:7; followed by hexane/EtOAc + 0.1% AcOH, 3:7) pure
[(CH3)3C], 27.0 [(CH3)3C], 26.9, 26.4, 23.8, 23.6 [2ϫC(CH3)2]
ppm. C17H28O7 (344.41): calcd. C 59.29, H 8.19; found C 59.15, H
8.12.
2d (3.20 g, 76% yield) as a syrup. Rf = 0.12 (hexane/EtOAc + 1%
AcOH, 1:1). [α]D = +31.1 (c 1.0, CHCl3). 1H NMR (200 MHz,
CD3CN): δ = 4.41 (d, J1Ј,2Ј = 8.1 Hz, 1 H, 1Ј-H), 4.30 (m, 2 H, 6Јa-
H, 6Јb-H), 4.22 (dd, J1,2 = 6.7 Hz, J2,3 = 4.7 Hz, 1 H, 2-H), 4.20
(d, 1 H, 1-H), 4.15–3.93 (m, 7 H, 3Ј-H, 4Ј-H, 5Ј-H, 4-H, 5-H, 6a-
H, 6b-H), 3.86 (dd, J3,4 = 1.5 Hz, 1 H, 3-H), 3.39, 3.38 (2s, each 3
H, 2ϫOCH3), 3.34 (dd, J2Ј,3Ј = 7.2 Hz, 1 H, 2Ј-H), 2.58 [m, 4 H,
CO(CH2)2CO], 1.44, 1.39, 1.34, 1.32 [4s, each 3 H, 2ϫC(CH3)2],
1.30 [s, 6 H, C(CH3)2] ppm. 13C NMR (50 MHz, CD3CN): see
Table 4 and δ = 174.2, 173.1 (2 ϫ C=O), 110.8, 110.5, 109.1
[3ϫC(CH3)2], 56.4, 54.3 (2ϫOCH3), 29.5, 29.1 [CO(CH2)2CO],
28.4, 27.6, 26.9, 26.6, 26.5, 25.2 [3ϫC(CH3)2] ppm. C27H44O15
(608.64): calcd. C 53.28, H 7.29; found C 53.20, H 7.18.
To a solution of 8 (10.0 g, 31.9 mmol) in MeOH (200 mL) was
added at room temperature a solution of 0.1  NaOMe in MeOH
(5 mL). After 24 h, the reaction mixture was neutralized with solid
CO2 and then concentrated to dryness. Purification of the residue
by flash chromatography (hexane/EtOAc, 3:2) afforded 1b (7.89 g,
95%) as a syrup. Rf = 0.42 (hexane/EtOAc, 3:2). [α]D = +37.9 (c
1.1, CHCl3), ref.[22] [α]D = +39 (c 1.0, CHCl3). The NMR spectro-
scopic data of 1b completely agreed with those reported in litera-
ture.[20]
4-O-[2-O-Acetyl-6-O-(3-carboxypropanoyl)-3,4-O-isopropylidene-β-
General Procedure for Succinylation of 1a–c: A mixture of the ap-
propriate sugar (1.0 mmol), succinic anhydride (1.2 equiv.), 4-di-
methylaminopyridine (0.1 equiv.) and Et3N (1 equiv.) in toluene
(4 mL) was stirred at reflux for 2.5 h and then concentrated at re-
duced pressure. The resulting residue was diluted with CH2Cl2
(5 mL), neutralized with AcOH, washed with H2O (7 mL) and the
aqueous phase extracted with CH2Cl2 (3ϫ7 mL). The organic
phase was dried with MgSO4, concentrated and the resulting resi-
due was purified by flash chromatography.
D-galactopyranosyl]-2,3:5,6-di-O-isopropylidene-aldehydo-D-glucose
Dimethyl Acetal (2e): A solution of 2d (2.52 g, 4.13 mmol), Ac2O
(10 mL) in pyridine (20 mL) was stirred at room temperature for
18 h and then repeatedly coevaporated with toluene at reduced
pressure. Purification of the residue by flash column chromatog-
raphy (hexane/EtOAc + 0.1 % AcOH, 1:1) afforded pure 2e
(2.47 mg, 91 %) as a syrup. Rf = 0.24 (hexane/EtOAc + 0.1 %
AcOH, 2:3). [α]D = +22.4 (c 1.0, CHCl3). 1H NMR (200 MHz,
CD3CN): δ = 4.86 (dd, J1Ј,2Ј = 8.3 Hz, J2Ј,3Ј = 6.6 Hz, 1 H, 2Ј-H),
4.55 (d, 1 H, 1Ј-H), 4.35–4.12 (m, 7 H, 1-H, 2-H, 5-H, 3Ј-H, 4Ј-H,
6Јa-H, 6Јb-H), 4.02 (dd, J2,3 = 6.4 Hz, J3,4 = 1.5 Hz, 1 H, 3-H),
3.98 (m, 1 H, 4-H), 3.91–3.72 (m, 3 H, 6a-H, 6b-H, 5Ј-H), 3.38,
3.37 (2s, each 3 H, 2ϫOCH3), 2.58 [m, 4 H, CO(CH2)2CO], 2.06
(s, 3 H, CH3CO), 1.45, 1.42, 1.29, 1.28, 1.27, 1.26 [6s, each 3 H,
3ϫC(CH3)2] ppm. 13C NMR (50 MHz, CD3CN): see Table 4 and
δ = 174.0, 173.1, 170.5 (3 ϫ C=O), 111.2, 110.9, 108.9 [3 ϫ C-
(CH3)2], 56.2, 54.2 (2ϫOCH3), 29.6, 29.1 [CO(CH2)2CO], 28.0,
27.7, 26.8, 26.5, 26.4, 24.8 [3 ϫ C(CH3)2], 21.1 (CH3CO) ppm.
C29H46O16 (650.68): calcd. C 53.53, H 7.13; found C 53.34, H 7.08.
3-O-(3-Carboxypropanoyl)-1,2:5,6-di-O-isopropylidene-α-D-glucofu-
ranose (2a): The succinylation of 1a (3.05 g, 11.7 mmol) afforded
2a (3.74 g, 88.6%) as a clear syrup after flash chromatographic
purification (hexane/EtOAc + 0.1% AcOH, 55:45). Rf = 0.35 (hex-
ane/EtOAc + 1% AcOH, 1:1). [α]D = –27.2 (c 1.1, CHCl3). 1H
NMR (200 MHz, CDCl3): see Table 1 and δ = 2.69 [m, 4 H,
CO(CH2)2CO], 1.52, 1.41, 1.32, 1.31 [4s, each 3 H, 2ϫC(CH3)2]
ppm. 13C NMR (50 MHz, CDCl3): see Table 2 and δ = 177.6
(COOH), 170.6 (COO), 112.3, 109.4 [2ϫC(CH3)2], 28.8 [CO(CH2)2-
CO], 26.8, 26.7, 26.1, 25.1 [2ϫC(CH3)2] ppm. C16H24O9 (360.36):
calcd. C 53.33, H 6.71; found C 53.52, H 6.78.
Alternatively, 2e (6.18 g, 90%) was prepared by succinylation of
1e[16] (6.20 g, 11.2 mmol) according to the general procedure de-
scribed above.
6-O-(3-Carboxypropanoyl)-1,2:3,5-di-O-isopropylidene-α-D-glucofu-
ranose (2b): The succinylation of 1b (5.78 g, 22.17 mmol) afforded
2b (5.75 g, 72%) as a solid after flash chromatographic purification
(EtOAc/iPrOH, 9:1). Rf = 0.35 (hexane/EtOAc + 0.1% AcOH, 2:3).
M.p. 94–96 °C (chrom). [α]D = +30.2 (c 1.1, CHCl3). 1H NMR
(200 MHz, CDCl3): see Table 1 and δ = 10.61 (br. s, 1 H, OH), 2.68
[br. s, 4 H, CO(CH2)2CO], 1.49, 1.37, 1.35, 1.33 [4s, each 3 H,
2ϫC(CH3)2] ppm. 13C NMR (50 MHz, CDCl3): see Table 2 and
δ = 177.7 (COOH), 171.8 (COO), 112.1, 100.9 [2ϫC(CH3)2], 28.7,
28.6 [CO(CH2)2CO], 26.9, 26.3, 23.7, 23.7 [2ϫC(CH3)2] ppm.
C16H24O9 (360.36): calcd. C 53.33, H 6.71; found C 53.12, H 6.76.
General Procedure for Succinylation of 3a–c: A mixture of the ap-
propriate dye (1 mmol), succinic anhydride (1.2 equiv.), 4-dimethyl-
aminopyridine (0.1 equiv.) and Et3N (1 equiv.) in CH2Cl2 (10 mL)
was stirred at room temperature. After 20 h, H2O (10 mL) was
added to the reaction mixture, which was then neutralized with
AcOH and extracted with CH2Cl2 (2ϫ10 mL). The organic phase
was dried with Na2SO4, concentrated and the resulting residue was
purified by flash chromatography eluting with the appropriate elut-
ing mixture.
6-O-(3-Carboxypropanoyl)-1,2:3,4-di-O-isopropylidene-β-D-galac- 4-(2-{ethyl[4-(phenyldiazenyl)phenyl]amino}ethoxy)-4-oxobutanoic
topyranose (2c): The succinylation of 1c (5.00 g, 19.2 mmol) af-
forded 2c (6.64 g, 96%) as a solid after crystallisation (EtOAc/hex-
Acid (4a): The succinylation of 3a (0.99 g, 3.67 mmol) afforded
pure 4a (1.34 g, 98 %) as an orange solid after flash chromato-
ane). Rf = 0.42 (EtOAc). [α]D = –38.7 (c 1.1, CHCl3). M.p. 105– graphic purification (EtOAc, then EtOAc + 0.1% AcOH). Rf =
107 °C (from EtOAc/hexane). 1H NMR (200 MHz, CDCl3): see
Table 1 and δ = 10.32 (br. s, 1 H, OH), 2.67 [br. s, 4 H, CO(CH2)2-
CO], 1.51, 1.45, 1.34, 1.33 [4s, each 3 H, 2ϫC(CH3)2] ppm. 13C
0.28 (CHCl3/EtOAc/MeOH, 8:1.7:0.3). M.p. 108–110 °C (chrom).
1H NMR (200 MHz, CDCl3): δ = 7.84 (m, 4 H, 2Ј-H, 6Ј-H, 8Ј-H,
12Ј-H), 7.65 (br. s, 1 H, COOH), 7.46 (m, 3 H, 3Ј-H, 4Ј-H, 5Ј-H),
NMR (50 MHz, CDCl3): see Table 2 and δ = 176.6 (COOH), 171.7 6.77 (m, 2 H, 9Ј-H, 11Ј-H), 4.30 (t, J = 6.3 Hz, 2 H, CH2O), 3.64
(COO), 109.1, 108.3 [2ϫC(CH3)2], 28.3 [CO(CH2)2CO], 25.4, 25.3,
24.4, 23.9 [2ϫ C(CH3)2] ppm. C16H24O9 (360.36): calcd. C 53.33,
H 6.71; found C 53.16, H 6.72.
(t, J = 6.3 Hz, 2 H, CH2CH2N), 3.48 (q, J = 7.1 Hz, 2 H,
CH3CH2N), 2.64 [m, 4 H, CO(CH2)2CO], 1.21 (t, J = 7.1 Hz, 3
H, CH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 177.8 (COOH),
592
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Eur. J. Org. Chem. 2007, 588–595

A New Class of Dyes – Glycoazodyes (GADs)
FULL PAPER
172.1 (COO), 153.1 (C-1Ј), 149.9 (C-10Ј), 143.6 (C-7Ј), 129.4, 128.9, [2ϫC(CH3)2], 12.2 (CH3) ppm. C32H41N3O9 (611.68): calcd. C
125.2, 122.2, 111.2 (Ar-CH), 61.8 (CH2O), 48.6, 45.5 (CH2N), 28.7 62.83, H 6.76, N 6.87; found C 63.01, H 6.92, N 6.99.
[CO(CH2)2CO], 12.2 (CH3) ppm. C20H23N3O4 (369.42): calcd. C
65.03, H 6.28, N 11.37; found C 64.98, H 6.15, N 11.25.
Protected GAD 6b: The condensation of 4b (157.7 mg, 0.381 mmol)
and 1a (118.9 mg, 0.457 mmol) afforded pure 6b (150.1 mg, 60%
yield) as a red syrup after flash chromatographic purification (hex-
4-[2-ethyl-({4-[(4-nitrophenyl)diazenyl]phenyl}amino)ethoxy]-4-oxo-
butanoic Acid (4b): The succinylation of 3b (5.32 g, 16.9 mmol) af-
ane/EtOAc, 3:2). Rf = 0.42 (hexane/EtOAc, 2:3). 1H NMR
(200 MHz, CDCl3): see Table 1 and δ = 8.32, 7.92 (AAЈXXЈ sys-
forded pure 4b (6.87 g, 98%) as a red solid after flash chromato-
tem, 4 H, 2Ј-H, 3Ј-H, 5Ј-H, 6Ј-H), 7.90, 6.80 (AAЈXXЈ system, 4
graphic purification (EtOAc, then EtOAc + 0.1% AcOH). Rf =
H, 8Ј-H, 9Ј-H, 11Ј-H, 12Ј-H), 4.33 (t, J = 6.3 Hz, 2 H, CH2O), 3.70
1
0.53 (EtOAc + 1% ACOH). M.p. 175–177 °C (chrom). H NMR
(t, J = 6.3 Hz, 2 H, CH2CH2N), 3.54 (q, J = 7.1 Hz, 2 H,
(200 MHz, CD3CN/D2O): δ = 8.30, 7.88 (AAЈXXЈ system, 4 H, 2Ј-
CH3CH2N), 2.67 [m, 4 H, CO(CH2)2CO], 1.51, 1.41, 1.32, 1.28 [4
H, 2Ј-H, 5Ј-H, 6Ј-H), 7.84, 6.86 (AAЈXXЈ system, 4 H, 8Ј-H, 9Ј-
s, each 3 H, 2ϫC(CH3)2], 1.26 (t, J = 7.1 Hz, 3 H, CH3) ppm. 13C
H, 11Ј-H, 12Ј-H), 4.26 (t, J = 5.8 Hz, 2 H, CH2O), 3.67 (t, J =
NMR (50 MHz, CDCl3): see Table 2 and δ = 172.0, 170.9
5.8 Hz, 2 H, CH2CH2N), 3.49 (q, J = 7.1 Hz, 2 H, CH3CH2N),
(2ϫC=O), 156.6 (C-1Ј), 151.1 (C-10Ј), 147.3 (C-4Ј), 143.7 (C-7Ј),
2.51 [m, 4 H, CO(CH2)2CO], 1.16 (t, J = 7.1 Hz, 3 H, CH3) ppm.
126.2, 124.6, 122.6, 111.3 (Ar-CH), 112.2, 109.3 [2ϫC(CH3)2], 61.6
13C NMR (50 MHz, CD3CN/D2O): δ = 177.8 (COOH), 174.5
(CH2O), 48.6, 45.6 (CH2N), 28.7 [CO(CH2)2CO], 26.8, 26.6, 26.1,
(COO), 157.6 (C-1Ј), 152.6 (C-10Ј), 148.2 (C-4Ј), 144.2 (C-7Ј),
127.0, 125.7, 123.3, 112.5 (Ar-CH), 62.0 (CH2O), 49.5, 46.3
(CH2N), 32.5, 31.4 [CO(CH2)2CO], 12.4 (CH3) ppm. C20H22N4O6
25.2 [2ϫC(CH3)2], 12.2 (CH3) ppm. C32H40N4O11(656.70): calcd.
C 58.53, H 6.14, N 8.53; found C 58.50, H 6.11, N 8.50.
(414.42): calcd. C 57.97, H 5.35, N 13.52; found C 57.91, H 5.33,
N 13.48.
6b was obtained also by the condensation of 3b (1.00 g, 3.18 mmol)
and 2a (1.12 g, 3.12 mmol). Flash chromatographic purification
(petroleum ether/EtOAc, 3:1) of the crude residue afforded pure 6b
(red syrup, 1.47 g, 72%) having NMR parameters identical to those
of the sample prepared above.
4-[2-ethyl-({4-[(2-chloro-4-nitrophenyl)diazenyl]phenyl}amino)-
ethoxy]-4-oxobutanoic Acid (4c): The succinylation of 3c (1.51 g,
4.3 mmol) afforded pure 4c (1.74 g, 90%) as a red solid after flash
chromatographic purification (EtOAc, then EtOAc + 0.1% AcOH),
Rf = 0.54 (EtOAc + 1 % AcOH). M.p. 98–100 °C. 1H NMR
(200 MHz, CDCl3): δ = 8.39 (d, J3Ј,5Ј = 2.4 Hz, 1 H, 3Ј-H), 8.14
(dd, J5Ј,6Ј = 8.9 Hz, 1 H, 5Ј-H), 7.94, 6.81 (AAЈXXЈ system, 4 H,
8Ј-H, 9Ј-H, 11Ј-H, 12-H), 7.78 (d, 1 H, 6Ј-H), 4.33 (t, J = 6.3 Hz,
2 H, CH2O), 3.70 (t, J = 6.3 Hz, 2 H, CH2CH2N), 3.54 (q, J =
7.0 Hz, 2 H, CH3CH2N), 2.66 [m, 4 H, CO(CH2)2CO], 1.26 (t, J
= 7.0 Hz, 3 H, CH3) ppm. 13C NMR (50 MHz, CDCl3): δ = 177.2
(COOH), 172.1 (COO), 153.0 (C-1Ј), 151.6 (C-10Ј), 147.2 (C-4Ј),
144.4 (C-7Ј), 134.8 (C-2Ј), 126.9, 126.9, 126.0, 122.6, 118.0, 111.5,
111.5 (Ar-CH), 61.6 (CH2O), 48.7, 45.8 (CH2N), 28.7, 28.6
[CO(CH2)2CO], 12.2 (CH3) ppm. C20H21ClN4O6 (448.87): calcd. C
53.52, H 4.72, N 12.48; found C 53.49, H 4.70, N 12.43.
Protected GAD 6c: The condensation of 4b (1.32 g, 3.19 mmol) and
1b (994.3 mg, 3.82 mmol) afforded pure 6c (1.80 g, 86%) as a red
syrup after flash chromatographic purification (hexane/EtOAc,
65:35). Rf = 0.52 (hexane/EtOAc, 2:3). 1H NMR (200 MHz,
CDCl3): see Table 1 and δ = 8.31, 7.93 (AAЈXXЈ system, 4 H, 2Ј-
H, 3Ј-H, 5Ј-H, 6Ј-H), 7.88, 6.79 (AAЈXXЈ system, 4 H, 8Ј-H, 9Ј-
H, 11Ј-H, 12Ј-H), 4.30 (t, J = 6.3 Hz, 2 H, CH2O), 3.68 (t, J =
6.3 Hz, 2 H, CH2CH2N), 3.53 (q, J = 7.1 Hz, 2 H, CH3CH2N),
2.66 [m, 4 H, CO(CH2)2CO], 1.49, 1.37, 1.36, 1.33 [4 s, each 3 H,
2 ϫ C(CH3)2], 1.26 (t, J = 7.1 Hz, 3 H, CH3) ppm. 13C NMR
(50 MHz, CDCl3): see Table 2 and δ = 172.0, 171.9 (2 ϫC=O),
156.6 (C-1Ј), 151.1 (C-10Ј), 147.3 (C-4Ј), 143.3 (C-7Ј), 126.2, 124.6,
122.6, 111.3 (Ar-CH), 112.2, 101.0 [2ϫC(CH3)2], 61.5 (CH2O),
48.6, 45.6 (CH2N), 28.8 [CO(CH2)2CO], 27.1, 26.4, 23.8, 23.7
[2ϫC(CH3)2], 12.2 (CH3) ppm. C32H40N4O11 (656.70): calcd. C
58.53, H 6.14, N 8.53; found C 58.75, H 6.05, N 8.33.
General Procedure for the Preparation of Protected GADs 6a–h: A
mixture of the appropriate monosuccinate (1 mmol), the appropri-
ate alcohol (1.2 equiv.), NЈ-(3-dimethylaminopropyl)-N-ethylcar-
bodiimide hydrochloride (1.2 equiv.), 4-dimethylaminopyridine
(0.28 equiv.) in THF (10 mL) was stirred at room temperature for
20 h and then concentrated at reduced pressure. The resulting resi-
due was diluted with EtOAc (15 mL) and washed with saturated
aqueous NaHCO3 (15 mL) and brine (15 mL). The organic phase
was dried with Na2SO4, concentrated and the resulting residue was
purified by flash chromatography eluting with the appropriate elut-
ing mixture.
Protected GAD 6d: The condensation of 2b (3.00 g, 8.32 mmol) and
3c (3.48 g, 9.95 mmol) afforded pure 6d (4.02 g, 70 %) as a red
syrup after flash chromatographic purification (hexane/EtOAc,
7:3). Rf = 0.54 (hexane/EtOAc, 3:2). 1H NMR (200 MHz, CDCl3):
see Table 1 and δ = 8.39 (d, J3Ј,5Ј = 2.4 Hz, 1 H, 3Ј-H), 8.16 (dd,
J5Ј,6Ј = 8.9 Hz, 1 H, 5Ј-H), 7.95, 6.80 (AAЈXXЈ system, 4 H, 8Ј-H,
9Ј-H, 11Ј-H, 12Ј-H), 7.78 (d, J = 8.9 Hz, 1 H, 6Ј-H), 4.29 (m, 2 H,
CH2O), 3.70 (t, J = 6.2 Hz, 2 H, CH2CH2N), 3.55 (q, J = 7.1 Hz,
2 H, CH3CH2N), 2.66 [m, 4 H, CO(CH2)2CO], 1.49, 1.36, 1.35,
1.33 [4 s, each 3 H, 2ϫC(CH3)2], 1.27 (t, J = 7.1 Hz, 3 H, CH3)
ppm. 13C NMR (50 MHz, CDCl3): see Table 2 and δ = 171.9, 171.8
(2ϫC=O), 151.5, 151.5 (C-1Ј, C-10Ј), 146.9 (C-4Ј), 144.2 (C-7Ј),
133.8 (C-2Ј), 126.8, 126.8, 125.8, 122.2, 117.8, 111.3, 111.3 (Ar-
CH), 112.1, 100.9 [2ϫC(CH3)2], 61.3 (CH2O), 48.6, 45.6 (CH2N),
28.7 [CO(CH2)2CO], 27.0, 26.3, 23.7, 23.6 [2 ϫ C(CH3)2], 12.1
(CH3) ppm. C32H39ClN4O11 (691.14): calcd. C 55.61, H 5.69, N
8.11; found C 55.58, H 5.76, N 8.04.
Protected GAD 6a: The condensation of 2a (1.00 g, 2.79 mmol) and
3a (899 mg, 3.35 mmol) afforded pure 6a (1.54 g, 90%) as a yellow–
orange solid foam after flash chromatographic purification (petro-
leum ether/EtOAc, 3:1). Rf = 0.42 (petroleum ether/EtOAc, 3:1).
1H NMR (200 MHz, CDCl3): see Table 1 and δ = 7.85 (m, 4 H,
2Ј-H, 6Ј-H, 8Ј-H, 12-H), 7.43 (m, 3 H, 3Ј-H, 4Ј-H, 5Ј-H), 6.76 (m,
2 H, 9Ј-H, 11Ј-H), 4.31 (t, J = 6.3 Hz, 2 H, CH2O), 3.61 (t, J =
7.1 Hz, 2 H, CH2CH2N), 3.43 (q, J = 7.1 Hz, 2 H, CH3CH2N),
2.62 [m, 4 H, CO(CH2)2CO], 1.51, 1.39, 1.30, 1.29 [4 s, each 3 H,
2 ϫ C(CH3)2], 1.19 (t, J = 7.1 Hz, 3 H, CH3) ppm. 13C NMR
(50 MHz, CDCl3): see Table 2 and δ = 171.8, 170.7 (2 ϫC=O),
152.9 (C-1Ј), 149.8 (C-10Ј), 143.5 (C-7Ј), 129.3, 128.7, 124.9, 122.0,
Protected GAD 6e: The condensation of 2c (500 mg, 1.39 mmol)
and 3a (448 mg, 1.66 mmol) afforded pure 6e (814 mg, 96%) as a
yellow–orange solid foam after flash chromatographic purification
(hexane/EtOAc, 3:2). Rf = 0.50 (petroleum ether/EtOAc/Et3N,
1
111.1 (Ar-CH), 112.1, 109.1 [2ϫC(CH3)2], 61.7 (CH2O), 48.5, 45.4 3:2:0.1). M.p. 37–39 °C (chrom). H NMR (200 MHz, CDCl3): see
(CH2N), 28.8, 28.7 [CO(CH2)2CO], 26.7, 26.6, 26.1, 26.0 Table 1 and δ = 7.85 (m, 4 H, 2Ј-H, 6Ј-H, 8Ј-H, 12Ј-H), 7.42 (m, 3
Eur. J. Org. Chem. 2007, 588–595
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
593

G. Bartalucci, R. Bianchini, G. Catelani, F. D’Andrea, L. Guazzelli
FULL PAPER
H, 3Ј-H, 4Ј-H, 5Ј-H), 6.77 (m, 2 H, 9Ј-H, 11Ј-H), 4.23 (m, 2 H, Deprotected GAD 5a: A solution of 6a (1.54 g, 2.51 mmol) in 90%
CH2O), 3.59 (t, J = 6.2 Hz, 2 H, CH2CH2N), 3.43 (q, J = 6.9 Hz, aq CF3COOH (20 mL) was stirred at room temperature for 1.5 h
2 H, CH3CH2N), 2.63 [m, 4 H, CO(CH2)2CO], 1.50, 1.43, 1.30, and then repeatedly coevaporated with toluene at reduced pressure.
1.29 [4 s, each 3 H, 2ϫC(CH3)2], 1.18 (t, J = 6.9 Hz, 3 H, CH3)
The resulting residue was diluted with CH2Cl2 and washed with
ppm. 13C NMR (50 MHz, CDCl3): see Table 2 and δ = 171.9 saturated aqueous NaHCO3. The organic phase was dried with
(2ϫC=O), 152.9 (C-1Ј), 149.8 (C-10Ј), 143.4 (C-7Ј), 129.2, 128.7, Na2SO4 and concentrated at reduced pressure to give 5a (1.08 g,
125.0, 122.0, 111.1 (Ar-CH), 109.3, 108.5 [2 ϫ C(CH3)2], 61.4
(CH2O), 48.4, 45.3 (CH2N), 28.7 [CO(CH2)2CO], 25.8, 25.7, 24.7,
81%) as a yellow powdery syrup. Rf = 0.25 (EtOAc/MeOH, 20:1)
as a mixture of α-pyranose, β-pyranose and β-furanose anomers in
24.2 [2ϫC(CH3)2], 12.0 (CH3) ppm. C32H41N3O9 (611.70): calcd. the ratio of 35:55:10, calculated on the basis of the relative C-1
1
C 62.83, H 6.76, N 6.87; found C 63.03, H 6.97, N 6.92.
signal intensities (see Table 3). H NMR (200 MHz, Me2SO): δ =
7.77 (m, 4 H, 2Ј-H, 6Ј-H, 8Ј-H, 12Ј-H, both anomers), 7.47 (m, 3
H, 3Ј-H, 4Ј-H, 5Ј-H, both anomers), 6.85 (m, 2 H, 9Ј-H, 11Ј-H,
both anomers), 6.53 (d, J1,2 = 4.4 Hz, 1 H, 1-H, α-pyranose), 5.05
(m, 2 H, 3-H, both anomers), 4.72–4.50 (m, 2 H, both anomers),
4.20–4.18 (m, 2 H, both anomers), 3.64–3.21 (m, 6 H, CH2O,
CH3CH2N, CH2CH2N, both anomers), 2.53 [m, 4 H, CO(CH2)2-
CO, both anomers], 1.12 (m, 3 H, CH3, both anomers) ppm. 13C
NMR (50 MHz, Me2SO): see Table 3 for the glycide portion and
for the succinyl and dye portions δ = 172.0, 171.6 (2ϫC=O), 152.5
(C-1Ј), 150.3 (C-10Ј) 142.7 (C-7Ј), 129.6, 129.2, 125.0. 121.8, 111.4
(ArCH), 60.8 (CH2O), 48.2 (CH3CH2N), 44.9 (CH2CH2N), 28.9
[CO(CH2)2CO], 12.0 (CH3) ppm. C26H33N3O9 (531.56): calcd. C
58.75, H 6.26, N 7.91; found C 58.91, H 6.48, N 8.07.
Protected GAD 6f: The condensation of 4b (496 mg, 1.20 mmol)
and 1c (374 mg, 1.44 mmol) afforded pure 6f (589 mg, 75%) as a
red syrup after flash chromatographic purification (hexane/EtOAc,
3:2). Rf = 0.53 (hexane/EtOAc, 2:3). 1H NMR (200 MHz, CDCl3):
see Table 1 and δ = 8.32, 7.92 (AAЈXXЈ system, 4 H, 2Ј-H, 3Ј-H,
5Ј-H, 6Ј-H), 7.90, 6.79 (AAЈXXЈ system, 4 H, 8Ј-H, 9Ј-H, 11Ј-H,
12Ј-H), 4.32 (t, J = 6.3 Hz, 2 H, CH2O), 3.69 (t, J = 6.3 Hz, 2 H,
CH2CH2N), 3.53 (q, J = 7.1 Hz, 2 H, CH3CH2N), 2.66 [m, 4 H,
CO(CH2)2CO], 1.51, 1.45, 1.33, 1.32 [4 s, each 3 H, 2ϫC(CH3)2],
1.25 (t, J = 7.1 Hz, 3 H, CH3) ppm. 13C NMR (50 MHz, CDCl3):
see Table 2 and δ = 172.1, 170.0 (2ϫC=O), 156.6 (C-1Ј), 151.1 (C-
10Ј), 147.3 (C-4Ј), 143.7 (C-7Ј), 126.2, 124.6, 122.6, 111.3 (Ar-CH),
109.6, 108.7 [2ϫC(CH3)2], 61.5 (CH2O), 48.7, 45.7 (CH2N), 28.9
[CO(CH2)2CO], 26.0, 25.9, 24.9, 24.4 [2ϫC(CH3)2], 12.2 (CH3)
ppm. C32H40N4O11 (656.70): calcd. C 58.53, H 6.14, N 8.53; found
C 58.52, H 6.11, N 8.48.
Deprotected GAD 5b: Compound 5b was obtained, starting from
6d (2.51 g, 3.63 mmol) in 94% yield through the same procedure
described above for the preparation of 5a. Product 5b is a red
´
amorphous, slightly hygroscopic solid. λmax (methanol) = 492 nm;
λmax (acetone) = 500 nm; λmax 3c (acetone) = 512 nm. Rf = 0.11
(EtOAc) as a mixture of α and β-pyranose anomers in the ratio of
about 1:1, calculated on the basis of the relative H-1 signal inten-
Protected GAD 6g: The condensation of 2c (1.04 g, 2.89 mmol) and
3c (1.21 g, 3.47 mmol) afforded pure 6 (503 mg, 70 %) as a red
syrup after flash chromatographic purification (hexane/EtOAc,
7:3). Rf = 0.50 (hexane/EtOAc, 2:3). 1H NMR (200 MHz, CDCl3):
see Table 1 and δ = 8.40 (d, J3Ј,5Ј = 2.4 Hz, 1 H, 3Ј-H), 8.16 (dd,
J5Ј,6Ј = 8.9 Hz, 1 H, 5Ј-H), 7.95, 6.71 (AAЈXXЈ system, 4 H, 8Ј-H,
9Ј-H, 11Ј-H, 12Ј-H), 7.78 (d, J = 8.9 Hz, 1 H, 6Ј-H), 4.28 (m, 2 H,
CH2O), 3.70 (t, J = 6.3 Hz, 2 H, CH2CH2N), 3.55 (q, J = 7.1 Hz,
2 H, CH3CH2N), 2.66 [m, 4 H, CO(CH2)2CO], 1.51, 1.45, 1.33,
1.32 [4 s, each 3 H, 2ϫC(CH3)2], 1.27 (t, J = 7.1 Hz, 3 H, CH3)
ppm. 13C NMR (50 MHz, CDCl3): see Table 2 and δ = 171.9
(2ϫC=O), 152.7 (C-1Ј), 151.5 (C-10Ј), 146.9 (C-4Ј), 144.1 (C-7Ј),
133.7 (C-2Ј), 126.8, 126.8, 125.8, 122.4, 117.8, 111.3, 111.3 (Ar-
CH), 109.4, 108.5 [2ϫC(CH3)2], 61.2 (CH2O), 48.6, 45.6 (CH2N),
28.7 [CO(CH2)2CO], 25.8, 25.7, 24.7, 24.3 [2 ϫ C(CH3)2], 12.1
(CH3) ppm. C32H39ClN4O11 (691.14): calcd. C 55.61, H 5.69, N
8.11; found C 55.79, H 5.59, N 8.02.
1
sities. H NMR (600 MHz, Me2SO): δ = 8.41 (d, J3Ј,5Ј = 2.1 Hz, 1
H, 3Ј-H, α- and β-pyranose), 8.22 (dd, J5Ј,6Ј = 8.9 Hz, 5Ј-H, 1 H,
α- and β-pyranose), 7.84 and 6.91 (AAЈXXЈ system, 4 H, 8Ј-H, 9Ј-
H, 11Ј-H, 12Ј-H, α- and β-pyranose), 7.76 (d, J = 8.9 Hz, 1 H, 6Ј-
H, α- and β-pyranose), 4.88 (d, J1,2 = 3.2 Hz, 0.5 H, 1-H, α-pyra-
nose), 4.28 (d, J1,2 = 7.9 Hz, 0.5 H, 1-H, β-pyranose), 4.36 and 3.98
(2m, 4 H, 6a-H, 6b-H, CH2O α- and β-pyranose), 3.78 (m, 2 H,
CH2CH2N, α- and β-pyranose), 3.70 (m, 1 H, 5-H, α-pyranose),
3.53 (br. q, 2 H, CH3CH2N, α- and β-pyranose), 3.55 (m, 2 H, 2-
H, 3-H, α-pyranose), 3.12–2.90 (m, 4 H, 4-H of α-pyranose and 2-
H, 3-H, 4-H of β-pyranose), 2.88 (m, 1 H, 5-H, β-pyranose), 2.53
and 2.48 [2m, each 4 H, CO(CH2)2CO, α- and β-pyranose], 1.46
(m, 3 H, CH3, α- and β-pyranose) ppm. 13C NMR (50 MHz,
Me2SO): see Table 3 for the glycide portion and, for the succinyl
and dye portions and δ = 172.8 (2ϫC=O), 152.8 (C-1Ј), 152.6 (C-
10Ј), 147.0 (C-4Ј), 143.9 (C-7Ј), 132.9 (C-2Ј), 127.2, 126.1, 123.3,
118.4, 112.2 (ArCH), 62.2 (CH2O), 48.8 (CH3CH2N), 45.8
( C H 2 C H 2 N ) , 2 9 . 1 [ C O ( C H 2 ) 2 C O ] , 1 2 . 5 ( C H 3 ) p p m .
C26H31ClN4O11 (611.01): calcd. C 51.11, H 5.11, N 9.17; found C
51.32, H 5.33, N 9.15.
Protected GAD 6h: The condensation of 2e (350 mg, 0.54 mmol)
and 3a (175 mg, 0.66 mmol) afforded pure 6h (270 mg, 55%) as a
yellow solid foam after flash chromatographic purification (hexane/
EtOAc, 1:1). Rf = 0.38 (petroleum ether/EtOAc, 1:1). 1H NMR
(200 MHz, CDCl3): δ = 7.84 (m, 4 H, 2Ј-H, 6Ј-H, 8Ј-H, 12Ј-H),
7.43 (m, 3 H, 3Ј-H, 4Ј-H, 5Ј-H), 6.77 (m, 2 H, 9Ј-H, 11Ј-H), 5.00
(m, 1 H, 2Ј-H), 4.76 (d, J1Ј,2Ј = 8.2 Hz, 1 H, 1Ј-H), 4.47–4.22 (m,
9 H, 2-H, 1-H, 6Јb-H, 3Ј-H, 6Јa-H, 4-H, 5-H, CH2CO), 4.13–4.05 Deprotected GAD 5c: Compound 5c (1.10 g) was obtained, starting
(m, 5 H, 6a-H, 6b-H, 3-H, 5Ј-H, 4Ј-H), 3.65 (t, J = 6.2 Hz, 2 H, from 6e (1.30 g, 2.13 mmol) in 97% yield through the same pro-
CH2CH2N), 3.49 (q, J = 7.1 Hz, 2 H, CH3CH2N), 3.40, 3.39 (2s, cedure described above for the preparation of 5a. λmax (methanol)
6 H, 2ϫOCH3), 2.63 [s, 4 H, (CH2)2CO], 2.10 (s, 3 H, CH3CO),
1.54, 1.46, 1.36, 1.35, 1.31, 1.30 [6 s, each 3 H, C(CH3)2], 1.23 (t,
= 409 nm, λmax (acetone) = 413 nm, λmax 3a (acetone) = 417 nm.
5c is a mixture of α-pyranose, β-pyranose and β-furanose anomers
J = 7.1 Hz, 3 H, CH3CH2N) ppm. 13C NMR (50 MHz, CDCl3): in the ratio of 35:55:10, calculated on the basis of the relative C-1
see Table 4 and δ = 174.0, 173.1, 170.5 (3ϫCO), 153.0 (C-1Ј), 149.8
(C-10Ј), 143.6 (C-7Ј), 129.3, 128.8, 125.1, 122.1, 111.3 (Ar-CH),
110.8, 110.6, 107.8, [3ϫC(CH3)2], 61.7 (CH2O), 48.7, 45.4 (CH2N),
28.8, 28.7 [CO(CH2)2CO], 27.6, 27.5, 26.3, 26.2, 26.1, 24.6
[3 ϫ C(CH3)2], 20.9 (CH3CO), 12.3 (CH3) ppm. C45H62N3O16
(901.99): calcd. C 59.92, H 7.04, N 4.66; found C 60.21, H 7.22, N
4.80.
signal intensities (see Table 3). Selected 1H NMR (200 MHz,
Me2SO) data (unresolved multiplets relative to all anomeric forms):
δ = 7.77 (m, 4 H, 2Ј-H, 6Ј-H, 8Ј-H, 12Ј-H), 7.46 (m, 3 H, 3Ј-H, 4Ј-
H, 5Ј-H), 6.84 (m, 2 H, 9Ј-H, 11Ј-H), 5.10–4.70 (m, 2 H), 4.21
(m, 2 H), 4.09 (m, 2 H), 3.70–3.30 (m, 7 H, CH2O, CH3CH2N,
CH2CH2N), 2.55 [m, 4 H, CO(CH2)2CO], 1.09 (m, 3 H, CH3) ppm.
13C NMR (50 MHz, Me2SO): see Table 3 for the glycide portion
594
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 588–595

A New Class of Dyes – Glycoazodyes (GADs)
FULL PAPER
and for the succinyl and dye portions δ = 172.0 (2ϫC=O), 152.5
(C-1Ј), 150.3 (C-10Ј), 142.6 (C-7Ј), 129.6, 129.2, 125.0, 121.9, 111.4
(ArCH), 61.7 (CH2O), 48.2 (CH3CH2N), 44.9 (CH3CH2N), 28.6
[CO(CH2)2CO], 12.0 (CH3) ppm. C26H33N3O9 (531.57): calcd. C
58.75, H 6.26, N 7.90; found C 58.65, H 6.20, N 7.86.
[1] M. Neamtu, I. Siminiceanu, A. Yediler, A. Kettrup, Dyes Pigm.
2002, 53, 93–99.
[2] H. Zollinger in Color Chemistry, 2nd ed., VCH, Weinheim,
1991, p. 187 and following pages.
[3] C. S. Poon, Q. Huang, P. C. Fung, Chemosphere 1999, 38,
1005–1014.
[4] U. Rott, R. Minke, Water Sci. Technol. 1999, 40, 137–144.
[5] a) R. Bianchini, L. Calucci, L. Lubello, C. Pinzino, Res. Chem.
Intermed. 2002, 28, 247–256; b) Y. Coque, E. Touraud, O.
Thomas, Dyes Pigm. 2002, 54, 17–23; c) C. Galindo, P. Jacques,
A. Kalt, Dyes Pigm. 2000, 30, 35–47; d) J. Riu, I. Schonsee, D.
Barcelò, C. Ràfols, Trends Anal. Chem. 1997, 16, 405–419; e)
C. A. Martin, O. M. Alfano, A. E. Cassano, Dyes Pigm. 2000,
60, 119–127; f) H. Ince, G. Tezvanlì, Dyes Pigm. 2001, 49, 145–
153.
[6] H. Selcuk, Dyes Pigm. 2005, 64, 217–222.
[7] G. Mascolo, A. Lopez, A. Bozzi, G. Tiravanti, Ozone Sci. Eng.
2002, 24, 236–244.
[8] For example, see: C. I. Pierce, J. R. Lloyd, J. T. Guthrie, Dyes
Pigm. 2003, 58, 179–196.
[9] a) P. Paraskeva, S. D. Lambert, N. J. D. Graham, Ozone Sci.
Eng. 1998, 20, 133–150; b) A. B. C. Alvares, C. Dlaper, S. A.
Parsons, Environ. Technol. 2001, 22, 409–427.
Deprotected GAD 5d: Compound 5d was obtained, starting from
6g (1.09 g, 1.58 mmol) in 92% yield through the same procedure
described above for the preparation of 5a. Product 5d is a red
amorphous solid. λmax (methanol) = 492 nm; λmax (acetone) =
499 nm; λmax 3c (acetone) = 512 nm. Rf = 0.12 (EtOAc) as a mix-
ture of α-pyranose, β-pyranose and β-furanose anomers in the ratio
of 32:49:19, calculated on the basis of the relative C-1 signal inten-
sities (see Table 3). 1H NMR (200 MHz, Me2SO): δ = 8.38 (m, 1
H, 3Ј-H), 8.20 (m, 1 H, 5Ј-H), 7.78 and 6.90 (2 m, 5 H, 6Ј-H, 8Ј-
H, 9Ј-H, 11Ј-H, 12Ј-H), 5.10–4.60 (m, 1 H), 4.25 (m, 2 H), 4.10 (m,
1 H), 3.80–3.20 (m, 9 H, CH2O, CH3CH2N, CH2CH2N), 2.56 [m,
4 H, CO(CH2)2CO], 1.16 (m, 3 H, CH3) ppm. 13C NMR (50 MHz,
Me2SO): see Table 3 for the glycide portion and for the succinyl
and dye portions δ = 171.8 (2ϫC=O), 152.3 (C-1Ј), 152.0 (C-10Ј),
146.7 (C-4Ј), 143.4 (C-7Ј), 132.3 (C-2Ј), 126.6 and 111.8 (C-8Ј, C-
9Ј, C-10Ј, C-11Ј), 125.6 (C-3Ј), 123.2 (C-5Ј), 118.0 (C-6Ј), 61.5
(CH2O), 48.3 (CH3CH2N), 45.1 (CH2CH2N), 28.5 [CO(CH2)2CO],
12.0 (CH3) ppm. C26H31ClN4O11 (611.01): calcd. C 51.11, H 5.11,
N 9.17; found C 51.41, H 5.08, N 9.07.
[10] For example, see: J. Lehmann, Carbohydrates Structure and Bi-
ology, Organic Chemistry Monograph Series, 1998, Thieme,
Stuttgart, New York.
[11] G. H. Coleman, D. E. Rees, R. L. Sundberg, C. M. McCloskey,
J. Am. Chem. Soc. 1945, 67, 381–386.
[12] P. Savarino, P. Piccinini, E. Montoneri, G. Viscardi, P. Quagli-
otto, E. Barni, Dyes Pigm. 2000, 47, 177–188.
[13] R. Bianchini, G. Bartalucci, G. Catelani, G. Seu, European Pat.
Appl. n. 04005253.4, deposit 03/05/2004.
[14] For example, see: J. Madsen, M. Bols, Carbohydrates in Chem-
istry and Biology, Part I (Eds.: B. Ernst, G. W. Hart, P. Sinaÿ),
Wiley-VCH, Weinheim, 2000, vol. I, pp. 449–466.
[15] P. L. Barili, G. Catelani, F. D’Andrea, F. De Rensis, P. Falcini,
Carbohydr. Res. 1997, 298, 75–84.
Deprotected GAD 5e: Compound 5e (818 mg) was obtained, start-
ing from 6h (1.20 g, 1.33 mmol) in 85% yield through the same
procedure described above for the preparation of 5a. Product 5e is
a yellow powdery syrup. Rf = 0.51 (EtOAc/MeOH, 4:1) as a mix-
ture of α- and β-pyranose anomers in the ratio of 3:2, calculated on
the basis of the relative H-1 signal intensities. 1H NMR (200 MHz,
CD3OD): δ = 7.89 (m, 4 H, 2Ј-H, 6Ј-H, 8Ј-H, 12Ј-H), 7.52 (m, 3
H, 3Ј-H, 4Ј-H, 5Ј-H), 6.96 (m, 2 H, 9Ј-H, 11Ј-H), 5.10 (d, J1,2
=
3.7 Hz, 1-H, α-pyranose); 4.52 (d, J1,2 = 7.7 Hz, 1-H, β-pyranose);
4.38–4.23 (m, 4 H), 3.86–3.77 (m, 6 H), 3.68–3.40 (m, 6 H, CH2O,
CH3CH2N, CH2CH2N), 2.65 [m, 4 H, CO(CH2)2CO], 2.11 (s, 3
H, CH3CO), 1.20 (t, 3 H, CH3CH2N) ppm. 13C NMR (50 MHz,
CD3OD): see Table 4 for the glycide portion and for the succinyl
and dye portions δ = 173.0, 172.8, 171.1 (3ϫC=O, α-pyranose),
172.5, 172.3, 171.2 (3ϫC=O, β-pyranose), 153.2 (C-1Ј, both ano-
mers), 150.7 (C-10Ј, both anomers), 143.5 (C-7Ј, both anomers),
129.4, 129.0, 125.1, 122.0, 111.4 (Ar-CH, both anomers), 60.7
(CH2O, β-pyranose), 60.3 (CH2O, α-pyranose), 48.5 (CH3CH2N,
both anomers), 45.2 (CH2CH2N, both anomers), 28.6 [CO(CH2)
2CO, both anomers], 19.8 (CH3CO, α-pyranose), 19.7 (CH3CO, β-
pyranose), 11.4 (CH3, both anomers) ppm. C34H45N3O15 (735.73):
calcd. C 55.50, H 6.16, N 5.71; found C 55.81, H 6.38, N 5.97.
[16] P. L. Barili, G. Catelani, F. D’Andrea, E. Mastrorilli, J. Car-
bohydr. Chem. 1997, 16, 1001–1010.
[17] H. Wahl, Y. Arnould, M. Simon, Bull. Soc. Chim. Fr. 1952,
366–369.
[18] a) K. Bock, C. Pedersen, H. Pedersen, Adv. Carbohydr. Chem.
Biochem. 1984, 42, 193–225; b) K. Bock, H. Thogersen, H.
Pedersen, Annu. Rep. NMR Spectrosc. 1982, 13, 1–57.
[19] Preliminary tinctorial experiments were carried out by “Italvel-
luti” Spa Company [Montemurlo (Prato), Italy], and by
Prof. G. Seu, University of Cagliari, Italy, and will be reported
in a next report specifically dealing with this topic.
[20] K. Bock, C. Pedersen, Adv. Carbohydr. Chem. Biochem. 1983,
41, 27–66.
[21] D. D Perrin, W. L. F. Armarengo, D. R. Perrin, Purification of
Laboratory Chemicals, 2nd ed, Pergamon Press, Oxford, 1980.
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Acknowledgments
[23] G. Catelani, F. D’Andrea, M. Landi, C. Zuccato, N. Bianchi,
G. Gambari, Carbohydr. Res. 2006, 341, 538–544.
Received: August 7, 2006
We specifically thank Regione Toscana, Technological Innovation
branch, and Italvelluti Spa Company, Montemurlo (Prato) Italy,
who fully granted this effort and continue to do so.
Published Online: November 27, 2006
Eur. J. Org. Chem. 2007, 588–595
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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