Synthesis pathway to carbohydrate-derived salicylidene hydrazides as ligands for oxovanadium complexes

Article abstract of DOI:10.1016/j.tet.2006.03.094

Salicylidene hydrazides represent important ligands forming oxovanadium complexes. Carbohydrate-derived chiral salicylidene hydrazides as ligands for metal ion complexation were synthesized for the first time. The pathway of the mild and selective synthesis starts from commercial saccharides like methyl-α-d-glucopyranoside and methyl-α-d-mannopyranoside. All synthesized carbohydrate-derived salicylidene hydrazides are able to form oxovanadium complexes. The mononuclear structure proposed for the complex of 1,2,3,4-tetra-O-methyl-α-d-glucopyranuronic acid salicylidene hydrazide is consistent with the analytical data (NMR, IR and MS).

Full text of DOI:10.1016/j.tet.2006.03.094

Tetrahedron 62 (2006) 5675–5681
Synthesis pathway to carbohydrate-derived salicylidene
hydrazides as ligands for oxovanadium complexes
b
b
a
J. Becher,a, I. Seidel, W. Plass and D. Klemm
*
aInstitute of Organic and Macromolecular Chemistry, Friedrich-Schiller-Universitat Jena,
Humboldtstraße 10, D-07743 Jena, Germany
¨
bInstitute of Inorganic and Analytical Chemistry, Friedrich-Schiller-Universitat Jena,
Carl-Zeiss-Promenade 10, D-07745 Jena, Germany
¨
Received 6 December 2005; revised 24 March 2006; accepted 27 March 2006
Available online 3 May 2006
Abstract—Salicylidene hydrazides represent important ligands forming oxovanadium complexes. Carbohydrate-derived chiral salicylidene
hydrazides as ligands for metal ion complexation were synthesized for the first time. The pathway of the mild and selective synthesis starts
from commercial saccharides like methyl-a-D-glucopyranoside and methyl-a-D-mannopyranoside. All synthesized carbohydrate-derived
salicylidene hydrazides are able to form oxovanadium complexes. The mononuclear structure proposed for the complex of 1,2,3,4-tetra-
O-methyl-a-D-glucopyranuronic acid salicylidene hydrazide is consistent with the analytical data (NMR, IR and MS).
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
Recently, we described the first structurally characterized
prototypes of copper complexes from aminodeoxysugars
and its efficient catalytic activity in catechol oxidation.14–17
Moreover, carbohydrate-derived chiral Mn(III)–salen com-
plexes are potent catalysts in enantiomeric epoxidation of
alkenes.18
Salicylidene hydrazides are versatile structural units that can
act as mono- or dianionic ONO tridentate donors. Oxovana-
dium complexes of these ligands have been used as enzyme
models for the active site of vanadium dependent haloper-
oxidases.1–3 Similar complexes, which have an additional
coordination site bound at a side chain also offer good halo-
peroxidase activity.4,5
The aim of the present paper is to extend and to confirm the
carbohydrate-based structure design of chiral transition
metal complexes with catalytic activity using salicylidene
hydrazides as ONO ligands and carbohydrates with or with-
out additional free hydroxyl groups. Therefore, an important
topic of the work was a concept for an easy synthesis of
Since haloperoxidases are known to catalyze enantioselec-
tive sulfoxidation6–9 as well as oxovanadium complexes
of tri- or tetradentate Schiff base ligands,10–13 such com-
plexes of salicylidene hydrazides with a chiral backbone
should be a good catalysts for enantioselective sulfoxidation
(Fig. 1).
a large variety of carbohydrate-derived salicylidene
hydrazides and its exemplification by typical examples.
Furthermore the complexation behaviour of these ligands
with vanadate was investigated.
2. Results and discussion
Carbohydrates as polyfunctional and chiral natural com-
pounds are—with growing importance—starting materials
and ligands for the synthesis of catalytic active transition
metal complexes.19–26 Due to the broad variety of configura-
tional and conformational principles of carbohydrates a
tuning of the complex structure and also of its catalytic ac-
tivity can be achieved by varying the carbohydrate moiety.
Moreover, the introduction of substituents into the carbo-
hydrate skeleton may influence complex properties like
Figure 1. Salicylidene hydrazides with a chiral carbohydrate backbone.
Keywords: Chiral salicylidene hydrazides; Carbohydrates; Selective synthe-
sis; Glucose-derived salicylidene hydrazide; Oxovanadium complexes.
* Corresponding author. Tel.: +49 3641 948264; fax: +49 3641 948202;
e-mail: jana.becher@uni-jena.de
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.03.094

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J. Becher et al. / Tetrahedron 62 (2006) 5675–5681
solubility and magnetic behaviour as well as the catalytic
activity—even if the substituent is not directly coordinated
to the metal.16
[1,2,3,4-tetra-O-methyl-a-D-glucopyranuronic acid salicyl-
idene hydrazidato] dioxo vanadate 24 could be obtained as
a yellow powder in 63% yield. The structure proposed for
the vanadium complex 24, which is consistent with the ana-
lytical data (quod infra), is shown in Figure 3. The 1H NMR
data of the complex verify the absence of the signals of the
aromatic OH-group and of the amide N–H proton (9.19 and
10.87 ppm, respectively). The 51V NMR spectrum recorded
in MeOD shows a single resonance in the expected range for
cis-dioxovanadium(v) complexes, i.e., at d¼ꢀ544 ppm with
In order to investigate the structural design in the field of
carbohydrate-based salicylidene hydrazides and their oxova-
nadium complexes we have synthesized a set of pyranosides
and open chain analogue (Fig. 2, 11 and 23), respectively.
Besides, the stereochemistry of the ligands (glucose and
mannose, see Fig. 2, 14 and 5) and the kind and amount of
functional substituents (ketal groups, ethers) at the carbo-
hydrate have been modified.
a peak width at half height of Dn ¼526 Hz. Mass spectro-
½
metry experiments have confirmed the formation of the
named complex. Infrared spectra show a deprotonation of
the ligand amide function since the C]O and N–H stretches
of the free ligand at 1711 and 3206 cmꢀ1, respectively, can
not be observed in the complex spectrum. Instead a strong
signal at 1617 cmꢀ1 occurs that can be assigned to the
–C]N–N]C-structural unit of the metal-bound salicyl-
idene hydrazide. It indicates a coordination of the enolate
form of the amide moiety.2,27 Furthermore two strong bands
are observed at 910 and 918 cmꢀ1 belonging to the stretching
vibrations of the cis-dioxovanadium moiety of the complex.
We developed a synthetic route that allows a selective
conversion to salicylidene hydrazides starting from any
purchasable saccharide with a primary OH-group. Scheme 1
shows this synthetic pathway considering methyl-2,3-O-
isopropylidene-a-D-mannuronic acid salicylidene hydrazide
5 starting from methyl-a-D-mannopyranoside 1 as an
example.
First, an isopropylidene ketal 2 is formed in order to increase
the solubility of the educt 1. In the next step, which is the key
step, the primary OH-group is oxidized selectively using
TEMPO-reagent. The carboxyl group is transformed into
the corresponding methylester 3 and then converted into
the hydrazide 4. Finally, the Schiff base 5 with salicylalde-
hyde is formed.
Attempts to form oxovanadium complexes of the ligands 5,
11 and 23 lead to mixtures of different coordination com-
pounds, that we were not able to separate up to now. But
51V NMR experiments show a formation of two species in
For transferring this pathway to other saccharides just the
introduction of the functional substituents has to be adapted
to the respective carbohydrate and its stereochemistry.
O
O
O
V
N
N
O
The ability of this type of ligands to form oxovanadium com-
plexes was demonstrated primarily using the salicylidene
hydrazide 20 without free OH donor groups. Therefore, a
solution of the ligand and equimolar amount of KVO3 in
methanol was refluxed for 24 h. After purification potassium
O
O
O
O
O
Figure 3. Proposed structure of the complex anion 24.
Figure 2. Set of carbohydrate-based salicylidene hydrazides.
Scheme 1. Reagents and conditions: (a) dimethoxy propane, p-toluene sulfonic acid, DMF, rt, 24 h; (b) TEMPO oxidation, rt, 2 h; methyl iodide, DMF, rt, 24 h;
(c) hydrazine monohydrate, ethanol, reflux, 3 h and (d) salicylaldehyde, ethanol, reflux, 6 h.

J. Becher et al. / Tetrahedron 62 (2006) 5675–5681
5677
each case. This suggests that the free OH-group at these car-
bohydrates is able to participate in the complex formation.
and 0.445 g (2.8 mmol) TEMPO (2,2,6,6-tetramethylpiperi-
dine 1-oxyl radical) were added. After cooling to 0 ꢂC
a cooled mixture of 55 ml sodium hypochloride (6% in wa-
ter), 27 ml of a saturated solution of NaHCO3 and 55 ml of
a saturated solution of NaCl in water was added slowly. The
reaction mixture was stirred vigorously for 2 h at 0 ꢂC until
completion (TLC control, eluent ethyl acetate/methanol
1:1). After evaporation in vacuum the product was dissolved
in methanol and filtered over silica gel suspended in metha-
nol in order to remove the inorganic salts. The crude acid
was converted into the methylester as described.29 Yield:
1.72 g (62%) colourless oil.
A first test in catalytic sulfoxidation reaction with 24 showed
a complete and selective conversion of the substrate to the
corresponding sulfoxide within 90 min. Therefore thioani-
sole was reacted with 1 mol % of 24 at room temperature
in CH2Cl2/MeOH (7:3) with 1.2 equiv of H2O2 as oxidation
agent. No enantioselectivity was observed, which may
be caused by the use of the protic solvent methanol, as
described in lit.10
1H NMR (CDCl3, 200 MHz): d 1.33, 1.49 (2s, 6H, 2ꢁ
–C(CH3)2), 3.45 (s, 3H, –OCH3), 3.80 (s, 3H, –COOCH3),
3.95–4.35 (m, 4H, H-2, H-3, H-4, H-5), 4.94 ppm (s, 1H,
H-1); 13C NMR (CDCl3, 50 MHz): d 25.31, 26.89 (2ꢁ
–C(CH3)2), 52.22 (–COOCH3), 55.33 (–OCH3), 69.01
(C-4), 69.87 (C-2), 74.16 (C-3), 76.05 (C-5), 98.53 (C-1),
109.59 (–C(CH3)2), 170.25 ppm (–COOCH3). Anal. Calcd
for C11H18O7: C, 50.38; H, 6.92%. Found: C, 49.69; H,
6.89.
3. Conclusion
The paper reports the preparation of the first carbohydrate-
derived chiral salicylidene hydrazides and its oxovanadium
complexes. An important topic of the work was the develop-
ment of an easy pathway to a large variety of chiral ligands
of this type starting from commercial carbohydrates. The
ligands 5, 11, 14, 20 and 23 form oxovanadium complexes
with VOꢀ3 . The proposed mononuclear structure of complex
24 can be proved by NMR, IR and MS and it is an active
catalyst for sulfoxidation.
4.1.3. Methyl-2,3-O-isopropylidene-a-D-mannuronic
acid hydrazide (4). Compound 3 3.3 g (12.5 mmol) and
1.25 g (25 mmol) hydrazine hydrate were refluxed in dry
ethanol (50 ml) for 3 h. After evaporation the crude product
was crystallized from methanol/ethyl acetate/n-hexane.
Yield: 1.91 g (58%) colourless needles.
Further investigations are concentrated on structure deter-
mination of the oxovanadium complexes and their catalytic
activity in sulfoxidation reactions.
4. Experimental
4.1. General
1H NMR (CDCl3, 200 MHz): d 1.31, 1.47 (2s, 6H, 2ꢁ
–C(CH3)2), 3.40 (s, 3H, –OCH3), 3.81 (dd, J¼9.0 Hz,
J¼6.2 Hz, 1H, H-4), 3.89 (s, 1H, –NH2), 4.03–4.21 (m,
3H, H-5, H-3, H-2), 4.34 (s, 1H, –OH), 4.93 (s, 1H, H-1),
7.86 ppm (s, 1H, –NHNH2); 13C NMR (CDCl3, 50 MHz):
d 25.75, 27.50 (–C(CH3)2), 55.70 (–OCH3), 68.42 (C-4),
70.12 (C-2), 74.29 (C-3), 76.62 (C-5), 98.53 (C-1), 109.74
(–C(CH3)2), 171.18 ppm (–CO–NH–). Anal. Calcd for
C10H18N2O6: C, 45.80; H, 6.92%; N, 10.68. Found: C,
45.81; H, 6.85; N, 10.81.
NMR spectra were recorded on a Bruker AC-200 spectro-
meter. IR spectra were measured on a Perkin–Elmer 2000
spectrometer. Mass spectra were carried out on a Finnigan
MAT SSQ710 or a Finnigan MAT 95XLTRAP. Elemental
analyses were acquired by use of a Leco CHNS 932. The
UV–vis data were recorded with a Cary 5000 from Varian.
Chemicals were obtained from Fluka and Aldrich, respec-
tively. TLC was conducted on Merck glass plates coated
with silica gel 60. Chromatography was performed using sil-
ica gel 60 (Particle size 0.063–0.2 mm) from Fluka Chemie
GmbH.
4.1.4. Methyl-2,3-O-isopropylidene-a-D-mannuronic
acid salicylidene hydrazide (5). Compound 4 1.0 g
(3.8 mmol) was suspended in dry methanol (30 ml) and re-
fluxed after adding 0.46 g (3.8 mmol) salicylaldehyde. After
6 h reaction was completed (TLC control ethyl acetate/
methanol 1:1). The solvent was removed and the crude prod-
uct was washed with ethanol. Yield: 1.25 g (90%).
4.1.1. Methyl-2,3-O-isopropylidene-a-D-mannopyrano-
side (2). Compound 2 was synthesized according to the
lit.28 starting from methyl-a-D-mannopyranoside 1.
1H NMR (CDCl3, 400 MHz): d 1.36, 1.45 (2s, 6H, 2ꢁ
–C(CH3)2), 3.36 (s, 3H, –OCH3), 3.50–4.11 (m, 6H, H-2,
H-3, H-4, H-5, H-6), 4.88 ppm (s, 1H, H-1); 13C NMR
(CDCl3, 100 MHz): d 26.01, 27.83 (2ꢁ–C(CH3)2), 54.99
(–OCH3), 62.28 (C-6), 69.29 (C-4), 69.54 (C-2), 75.40
(C-3), 78.25 (C-5), 98.38 (C-1), 109.65 ppm (–C(CH3)2).
Anal. Calcd for C10H18O6: C, 51.27; H, 7.75. Found: C,
51.36; H, 7.60.
1H NMR (CDCl3, 200 MHz): d 1.26, 1.36 (s, 3H, –C(CH3)2),
3.50 (s, 3H, –OCH3), 4.00 (m, 1H, H-4), 4.17–4.32 (m, 4H,
H-5, H-3, H-2, –OH), 5.03 (s, 1H, H-1), 6.87–7.03 (m, 2H,
H-3Ar, H-5Ar), 7.21 (dd, J¼7.7 Hz, J¼1.7 Hz, 1H, H-4Ar),
7.29–7.37 (m, 1H, H-6Ar), 8.41 (s, 1H, –CH]N–), 9.54 (s,
1H, Ar–OH), 10.80 ppm (s, 1H, –CO–NH–); 13C NMR
(CDCl3, 50 MHz): d 25.26, 27.05 (–C(CH3)2), 55.70
(–OCH3), 69.18 (C-4), 69.48 (C-2), 73.70 (C-3), 75.86
(C-5), 98.38 (C-1), 109.87 (–C(CH3)2), 116.66 (C-3Ar),
117.05 (C-1Ar), 119.09 (C-5Ar), 130.83 (C-6Ar), 132.07
(C-4Ar), 152.21 (–CH]N–), 158.41 (C-2Ar), 166.17 ppm
(–CO–NH–). Anal. Calcd for C17H22N2O7: C, 55.73; H,
6.05; N, 7.65. Found: C, 55.74; H, 5.71; N, 7.51.
4.1.2. Methyl-2,3-O-isopropylidene-a-D-mannuronic
acid methylester (3). Compound 2 2.5 g (10.6 mmol) was
dissolved in 55 ml ethyl acetate, 31 ml of a saturated aque-
ous solution of NaHCO3, 0.3 g (1.6 mmol) TBAF trihydrate

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J. Becher et al. / Tetrahedron 62 (2006) 5675–5681
4.1.5. Methyl-4,6-O-benzylidene-a-D-glucopyranoside
(6). Methyl-a-D-glucopyranoside was reacted as described
in lit.30 to give 6.
1H NMR (DMSO-d6, 200 MHz): d 3.07 (dd, J¼9.6 Hz,
J¼3.2 Hz, 1H, H-2), 3.18–3.69 (m, 2H, H-3, H-4), 3.28,
3.31, 3.42 (3s, 9H, 3ꢁ–OCH3), 4.27 (s 2H, –NH2), 4.79
(d, J¼3.2 Hz, 1H, H-5), 5.27 (d, J¼5.6 Hz, 1H, H-1),
9.35 ppm (s, 1H, –NHNH2); 13C NMR (DMSO-d6,
50 MHz): d 54.55, 57.24, 59.73 (3ꢁ–OCH3), 70.14 (C-5),
70.27 (C-3), 80.18 (C-2), 82.14 (C-4), 97.08 (C-1),
167.51 ppm (–CO–NH–). Anal. Calcd for C9H18O6N2:
C, 43.20; H, 7.25; N, 11.19. Found: C, 43.24; H, 7.34;
N, 11.11.
1H NMR (CDCl3, 250 MHz): d 3.42–3.83 (m, 5H, H-2, H-3,
H-5, H-6), 3.42 (s, 3H, –OCH3), 4.27 (dd, J¼8.8 Hz,
J¼3.0 Hz, 1H, H-4), 4.74 (d, J¼3.8 Hz, 1H, H-1), 5.50 (s,
1H, Ph–CH), 7.34–7.37 (m, 3H, H-3Ar, H-4Ar, H-5Ar),
7.47–7.53 ppm (m, 2H, H-2Ar, H-6Ar); 13C NMR (CDCl3,
60 MHz): d 55.49 (–OCH3), 62.35 (C-5), 68.90 (C-6),
71.53 (C-3), 72.79 (C-2), 80.93 (C-4), 99.82 (C-1), 101.90
(Ph–CH), 126.33 (C-2Ar C-6), 127.03 (C-3Ar C-5Ar),
128.97 (C-4Ar), 137.06 ppm (C-1Ar). Anal. Calcd for
C14H18O6: C, 59.57; H, 6.43. Found: C, 59.70; H, 6.32.
4.1.10. 1,2,3-Tri-O-methyl-a-D-glucopyranuronic acid
salicylidene hydrazide (11). The reaction was carried out
like 5. The crude product was purified by column chro-
matography (eluent: ethyl acetate). Compound 10 0.60 g
(2.4 mmol) gave 0.68 g (80%) 11.
4.1.6. 4,6-O-Benzylidene-1,2,3-tri-O-methyl-a-D-gluco-
pyranoside (7). Synthesis was carried out according to
Ref. 31 starting from 6.
1H NMR (CDCl3, 200 MHz): d 3.20 (dd, J¼9.6 Hz,
J¼3.5 Hz, 1H, H-2), 3.47–3.75 (m, 2H, H-3, H-4), 3.47,
3.52, 3.65 (3s, 9H, 3ꢁ–OCH3), 4.17 (d, J¼9.8 Hz, 1H, H-
5), 4.91 (d, J¼3.6 Hz, 1H, H-1), 6.83–6.99 (m, 2H, H-3Ar,
H-5Ar), 7.16 (dd, J¼7.7 Hz, J¼1.7 Hz, 1H, H-4Ar), 7.26–
7.34 (m, 1H, H-6Ar), 8.35 (s, 1H, –CH]N–), 9.41 (s, 1H,
Ar–OH), 10.75 ppm (s, 1H, –CO–NH–); 13C NMR
(CDCl3, 50 MHz): d 56.10, 59.32, 61.24 (3ꢁ–OCH3),
69.15 (C-5), 73.02 (C-3), 80.44 (C-2), 81.80 (C-4), 98.27
(C-1), 116.94 (C-3Ar), 117.39 (C-1Ar), 119.46 (C-5Ar),
131.16 (C-6Ar), 132.47 (C-4Ar), 152.72 (–CH]N–),
158.74 (C-2Ar), 166.99 ppm (–CO–NH–). Anal. Calcd for
C16H22N2O7: C, 54.23; H, 6.26; N, 7.91. Found: C, 53.61;
H, 6.43; N, 7.46.
1H NMR (CDCl3, 200 MHz): d 3.23 (dd, J¼9.1 Hz,
J¼3.6 Hz, 1H, H-2), 3.50–3.83 (m, 4H, H-6, H-5, H-3),
3.44, 3.55, 3.64 (3s, 9H, 3ꢁ–OCH3), 4.28 (dd, J¼9.3 Hz,
J¼4.0 Hz, 1H, H-4), 4.86 (d, J¼3.6 Hz, 1H, H-1), 5.45 (s,
1H, Ph–CH), 7.33–7.4 (m, 3H, H-3Ar, H-4Ar, H-5Ar), 7.46–
7.53 ppm (m, 2H, H-2Ar, H-6Ar); 13C NMR (CDCl3,
50 MHz): d 54.93, 59.00, 60.65 (3ꢁ–OCH3), 61.92 (C-5),
68.74 (C-6), 79.53 (C-4), 81.11 (C-3), 81.84 (C-2), 98.10
(C-1), 101.05 (Ph–CH), 125.75 (C-2Ar C-6), 127.86 (C-3Ar
C-5Ar), 128.59 (C-4Ar), 137.06 ppm (C-1Ar). Anal. Calcd
for C16H22O6: C, 61.96; H, 7.15. Found: C, 62.20; H, 7.28.
4.1.7. 1,2,3-Tri-O-methyl-a-D-glucopyranoside (8). Com-
pound 8 was prepared by conversion of 7 as described.32
4.1.11. 1-O-Methyl-a-D-glucopyranuronic acid methyl-
ester (12). Procedure like that of 9. Methyl-a-D-glucopyrano-
side 3.88 g (20 mmol) gave 3.19 g (72%) as a colourless oil.
1H NMR (methanol-d3, 200 MHz): d 3.29–3.37 (m, 2H, H-2,
H-3), 3.41, 3.46, 3.48 (3s, 9H, 3ꢁ–OCH3), 3.67–3.83 (m,
4H, H-4, H-5, H-6), 4.85 ppm (d, J¼3.4 Hz, 1H, H-1); 13C
NMR (methanol-d3, 50 MHz): d 55.34, 58.67, 61.21 (3ꢁ
–OCH3), 62.48 (C-5), 71.31 (C-6), 73.43 (C-3), 82.82
(C-2), 84.45 (C-4), 98.52 ppm (C-1). Anal. Calcd for
C9H18O6: C, 48.64; H, 8.16. Found: C, 48.72; H, 8.15.
1H NMR (DMSO-d6, 200 MHz): d 3.15 (d, J¼5.2 Hz, 1H,
H-2), 3.27 (s, 3H, –OCH3), 3.47 (s, 1H, –OH), 3.65 (s, 3H,
–COOCH3), 3.78 (s, 1H, –OH), 3.84 (s, 1H, –OH), 4.58
(d, J¼3.4 Hz, 1H, H-3), 4.88 (d, J¼6.2 Hz, 1H, H-4), 4.95
(d, J¼4.6 Hz, 1H, H-5), 5.27 ppm (d, J¼5.8 Hz, H-1); 13C
NMR (DMSO-d6, 50 MHz): d 51.90 (–COOCH3), 54.97
(–OCH3), 71.49 (H-4), 71.61 (H-2), 71.75 (H-3), 72.71
(H-5), 100.67 (H-1), 170.01 ppm (–COOCH3). Anal. Calcd
for C8H14O7: C, 43.24; H, 6.35. Found: C, 42.87; H, 6.85.
4.1.8. 1,2,3-Tri-O-methyl-a-D-glucopyranuronic acid
methylester (9). Oxidation of 2.0 g (9 mmol) 8 was per-
formed like 3. The crude acid was treated as describe to
obtain the methylester.33 Yield: 1.94 g (86%) of a colourless
oil.
4.1.12. 1-O-Methyl-a-D-glucopyranuronic acid hydra-
zide (13). Compound 12 3.13 g (14.1 mmol) was treated
like 4. Crystallization from methanol gave 2.29 g (73%) as
colourless needles.
1H NMR (CDCl3, 250 MHz): d 3.21 (dd, J¼9.2 Hz,
J¼3.4 Hz, 1H, H-2), 3.45–3.70 (m, 2H, H-3, H-4), 3.43,
3.46, 3.58 (3s, 9H, 3ꢁ–OCH3), 3.77 (1s, 3H, –COOCH3),
4.08 (d, J¼9.5 Hz, 1H, H-5), 4.86 ppm (d, J¼3.4 Hz, 1H,
H-1); 13C NMR (CDCl3, 60 MHz): d 52.64 (COOCH3),
55.82, 58.97, 61.07 (3ꢁ–OCH3), 70.52 (C-5), 71.63 (C-3),
80.74 (C-2), 81.67 (C-4), 97.96 (C-1), 170.69 ppm
(COOCH3). Anal. Calcd for C10H18O7: C, 48.00; H, 7.25.
Found: C, 47.93; H, 7.00.
1H NMR (DMSO-d6, 200 MHz): d 3.16 (m, 1H, H-2), 3.36
(s, 3H, –OCH3), 3.47, 3.65, 3.70 (3s, 3H, 3ꢁ–OH), 4.25
(s, 2H, –NH2), 4.51 (d, J¼3.6 Hz, 1H, H-3), 4.77 (d,
J¼6.2 Hz, 1H, H-4), 4.81 (d, J¼4.4 Hz, 1H, H-5), 5.02 (d,
J¼4.2 Hz, H-1), 9.29 ppm (–NHNH2); 13C NMR (DMSO-
d6, 50 MHz): d 54.88 (–OCH3), 70.68 (H-4), 71.24 (H-2),
71.56 (H-3), 72.98 (H-5), 100.45 (H-1), 167.88 ppm
(–CO–NH–). Anal. Calcd for C7H14N2O6: C, 37.84; H,
6.35; N, 12.61. Found: C, 37.76; H, 6.38; N, 12.48.
4.1.9. 1,2,3-Tri-O-methyl-a-D-glucopyranuronic acid hy-
drazide (10). Procedure like that of 4. The product precipi-
tated, was filtered and washed with ethyl acetate. Compound
9 1.64 g (6.55 mmol) gave 1.40 g (85%) as colourless
needles.
4.1.13. 1-O-Methyl-a-D-glucopyranuronic acid salicyl-
idene hydrazide (14). Procedure like that of 5. The crude

J. Becher et al. / Tetrahedron 62 (2006) 5675–5681
5679
product was crystallized from ethyl acetate/methanol (2:1).
Compound 13 0.50 g (2.3 mmol) gave 0.59 g (78%) 14.
and formation of the corresponding methylester was per-
formed like 3. Purification of the crude product by column
chromatography with ethyl acetate gave 3.91 g (70%) as
a yellow oil.
1H NMR (acetone-d6, 200 MHz): d 3.31 (d, J¼5.0 Hz, 1H,
H-2), 3.43 (s, 3H, –OCH3), 3.62–3.70 (m, 2H, H-3, H-4),
3.83 (d, J¼7.4 Hz, 1H, –OH), 4.10 (d, J¼9.2 Hz, 1H,
H-5), 4.26 (d, J¼3 Hz, 1H, –OH), 4.51 (d, J¼3 Hz, 1H,
–OH), 4.77 (d, J¼3.6 Hz, 1H, H-1), 6.87–6.95 (m, 2H,
H-3Ar, H-5Ar), 7.27–7.36 (m, 2H, H-4Ar, H-6Ar), 8.54 (s,
1H, –CH]N–), 10.96 (s, 1H, Ar–OH), 11.38 ppm (s, 1H,
–CO–NH–); 13C NMR (acetone-d6, 50 MHz): d 55.77
(–OCH3), 71.06 (H-4), 72.45 (H-2), 73.22 (H-3), 74.05
(H-5), 101.14 (H-1), 117.29 (C-3Ar), 118.46 (C-1Ar),
119.75 (C-5Ar), 131.63 (C-6Ar), 132.15 (C-4Ar), 151.51
(–CH]N–), 159.19 (C-2Ar), 167.02 ppm (–CO–NH–).
Anal. Calcd for C14H18N2O7: C, 51.53; H, 5.56; N, 8.59.
Found: C, 50.74; H, 6.61; N, 7.41.
1H NMR (CDCl3, 200 MHz): d 3.15 (dd, J¼14.6 Hz,
J¼3.4 Hz, 1H, H-2), 3.33–3.53 (m, 2H, H-3, H-4), 4.01 (d,
J¼12.3 Hz, 1H, H-5), 3.41, 3.47, 3.48, 3.58 (4s, 12H, 4ꢁ
–OCH3), 3.78 (s, 3H, –COOCH3), 4.81 ppm (d, J¼3.6 Hz,
1H, H-1); 13C NMR (CDCl3, 50 MHz):
d 52.51
(–COOCH3), 55.58, 59.14, 60.46, 60.94 (4ꢁ–OCH3),
69.90 (C-5), 81.18 (C-3), 81.21 (C-2), 82.86 (C-4), 98.06
(C-1), 170.11 ppm (–COOCH3). Anal. Calcd for
C11H20O7: C, 49.99; H, 7.63. Found: C, 50.16; H, 7.53.
4.1.18. 1,2,3,4-Tetra-O-methyl-a-D-glucopyranuronic
acid hydrazide (19). Procedure like that of 4. The product
precipitated, was filtered and washed with ethyl acetate.
Yield: 3.90 g (14.7 mmol) 18 gave 3.57 g (92%) 19.
4.1.14. 1-O-Methyl-6-O-triphenylmethyl-a-D-glucopyra-
nose (15). Synthesized according to lit.34
1H NMR (CDCl3, 200 MHz): d 3.18 (dd, J¼3.6 Hz,
J¼9.7 Hz, 1H, H-2), 3.24–3.36 (m, 2H, H-3, H-4), 3.87
(d, J¼10.0 Hz, 1H, H-5), 3.38, 3.47, 3.47, 3.57 (4s,
12H, 4ꢁ–OCH3), 4.82 (d, J¼3.4 Hz, 1H, H-1), 7.44 ppm
(s, 1H, –NHNH2); 13C NMR (CDCl3, 50 MHz): d 55.76,
59.13, 60.62, 60.95 (4ꢁ–OCH3), 69.47 (C-5), 81.06 (C-
3), 81.63 (C-2), 83.04 (C-4), 97.87 (C-1), 169.81 ppm
(–CO–NH–NH2). Anal. Calcd for C10H20N2O6: C,
45.45; H, 7.63; N, 10.60. Found: C, 44.56; H, 7.81; N,
10.37.
1H NMR (DMSO-d6, 250 MHz): d 3.03 (t, J¼8.2 Hz, 2H,
H-6), 3.26 (d, J¼9.6 Hz, 1H, H-4), 3.42 (d, J¼9.4 Hz, 1H,
H-3), 3.60 (t, J¼7.6 Hz, 1H, H-2), 4.07 (m, 1H, H-5), 3.37
(s, 3H, –OCH3), 4.61 (d, J¼3.5 Hz, 1H, H-1), 7.15–7.38
(m, 15H, –C(Ph)3); 13C NMR (CDCl3, 250 MHz): d 55.11
(–OCH3), 63.89 (C-6), 70.20 (C-5), 71.43 (C-3), 72.05
(C-2), 74.48 (C-4), 86.82 (–C(Ph)3), 99.12 (C-1), 127.18
(C-4Ar), 127.91 (C-3Ar), 128.68 (C-2Ar), 143.83 ppm
(C-1Ar). Anal. Calcd for C26H28O6: C, 71.54; H, 6.47.
Found: C, 72.14; H, 6.89.
4.1.19. 1,2,3,4-Tetra-O-methyl-a-D-glucopyranuronic
acid salicylidene hydrazide (20). Compound 19 0.5 g
(1.9 mmol) was treated like 5. Crystallization in methanol/
ethyl acetate (1:4) gave 0.53 g (74%) as a colourless solid.
4.1.15. 1,2,3,4-Tetra-O-methyl-6-O-triphenylmethyl-a-D-
glucopyranose (16). Compound 15 12.25 g (28.1 mmol)
was treated like 7. Crystallization of the crude product in
methanol gave 10.08 g (75%) as colourless needles.
1H NMR (CDCl3, 200 MHz): d 3.22 (dd, J¼3.4 Hz,
J¼6.2 Hz, 1H, H-2), 3.29–3.60 (m, 2H, H-4, H-3), 3.46,
3.54, 3.57, 3.64 (4s, 12H, 4ꢁ–OCH3), 4.10 (d, J¼12.5 Hz,
1H, H-5), 4.92 (d, J¼3.4 Hz, 1H, H-1), 6.87–7.03 (m, 2H,
H-3Ar, H-5Ar), 7.20–7.32 (m, 2H, H-4Ar, H-6Ar), 8.47 (s,
1H, –CH]N–), 9.19 (s, 1H, Ar–OH), 10.87 ppm (s, 1H,
–CO–NH–); 13C NMR (CDCl3, 50 MHz): d 55.64, 58.89,
60.42, 60.71 (4ꢁ–OCH3), 69.32 (C-5), 80.74 (C-3), 81.60
(C-2), 82.77 (C-4), 97.66 (C-1), 116.89 (C-3Ar), 116.99
(C-1Ar), 119.02 (C-5Ar), 130.71 (C-6Ar), 131.83 (C-4Ar),
151.72 (–CH]N–), 158.34 (C-2Ar), 164.57 ppm (–CO–
NH–). Anal. Calcd for C17H24N2O7: C, 55.43; H, 6.57; N,
7.60. Found: C, 55.51; H, 6.51; N, 7.64.
1H NMR (CDCl3, 250 MHz): d 3.13 (dd, J¼4.4 Hz,
J¼10.0 Hz, 1H, H-2), 3.33–3.65 (m, 5H, H-3, H-4, H-5,
H-6), 3.33, 3.48, 3.59, 3.65 (4s, 12H, 4ꢁ–OCH3), 4.94 (d,
J¼3.5 Hz, 1H, H-1), 7.26–7.54 ppm (m, 15H, –C(Ph)3);
13C NMR (CDCl3, 250 MHz): d 54.95, 59.04, 60.38, 60.96
(4ꢁ–OCH3), 62.44 (C-6), 70.10 (C-5), 79.98 (C-3), 81.90
(C-2), 83.74 (C-4), 86.25 (–OC(Ph)3), 97.32 (C-1), 126.94
(C-4Ar), 127.74 (C-2Ar), 128.78 (C-3Ar), 144.06 ppm
(C-1Ar). Anal. Calcd for C29H34O6: C, 72.78; H, 7.16.
Found: C, 72.99; H, 7.30.
4.1.16. 1,2,3,4-Tetra-O-methyl-a-D-glucopyranose (17).
Treating of 16 as shown in Ref. 35 gave 17.
4.1.20. 3,4,5,6-Di-O-isopropylidene-D-gluconic acid
methylester (21). Synthesis was carried out according to
lit.36 starting from D-gluconic acid-d-lactone.
1H NMR (CDCl3, 250 MHz): d 3.09 (dd, J¼3.6 Hz,
J¼9.6 Hz, 1H, H-2), 3.44–3.58 (m, 2H, H-3, H-4), 3.66
(dd, J¼11.7 Hz, J¼4.0 Hz, 1H, H-6), 3.76 (dd, J¼11.7 Hz,
J¼2.9 Hz, 1H, H-5), 3.34, 3.45, 3.50, 3.56 (4s, 12H, 4ꢁ
–OCH3), 4.73 ppm (d, J¼3.6 Hz, 1H, H-1); 13C NMR
(CDCl3, 250 MHz): d 55.13, 59.02, 60.54, 60.83 (4ꢁ
–OCH3), 61.91 (C-6), 70.54 (C-5), 79.61 (C-3), 81.82
(C-2), 83.37 (C-4), 97.48 ppm (C-1). Anal. Calcd for
C10H20O6: C, 50.84; H, 8.53. Found: C, 52.08; H, 8.93.
1H NMR (CDCl3, 250 MHz): d 1.37, 1.39 (2s, 6H, –C(CH3)2),
1.41, 1.45 (2s, 6H, –C(CH3)2), 2.44 (s, –OH), 3.86 (s, 3H,
–COOCH3), 3.99–4.24 (m, 5H, H-3, H-4, H-5, H-6),
4.37 ppm (dd, J¼9.1 Hz, J¼2.3 Hz, 1H, H-2); 13C NMR
(CDCl3, 63 MHz): d 25.27, 26.53, 26.69, 27.16 (2ꢁ
–C(CH3)2), 52.73 (–COOCH3), 67.89 (C-6), 69.43 (C-5),
76.45 (C-4), 77.27 (C-3), 80.89 (C-2), 109.87, 110.09 (2ꢁ
–C(CH3)2), 173.02 ppm (–COOCH3). Anal. Calcd for
C13H22O7: C, 53.78; H, 7.64. Found: C, 53.48; H, 7.79.
4.1.17. 1,2,3,4-Tetra-O-methyl-a-D-glucopyranuronic
acid methylester (18). Oxidation of 5.00 g (21 mmol) 17

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J. Becher et al. / Tetrahedron 62 (2006) 5675–5681
4.1.21. 3,4,5,6-Di-O-isopropylidene-D-gluconic acid hy-
drazide (22). Compound 21 4.11 g (14.2 mmol) was treated
like 4. Crystallization from ethyl acetate/n-hexane gave
3.81 g (92%) 22.
51V NMR (methanol-d3, 105 MHz):
d
ꢀ544 ppm
(n ¼526 Hz). Anal. Calcd for C17H22N2O9VK$H2O: C,
½
40.32; H, 4.78; N, 5.53. Found: C, 40.34; H, 4.58; N, 5.95.
1H NMR (CDCl3, 200 MHz): d 1.30, 1.35 (2s, 6H,
–C(CH3)2), 1.38 (s, 6H, –C(CH3)2), 3.83–3.99 (m, 2H, H-
6), 4.03–4.15 (m, 2H, H-5, H-4), 4.29 (d, J¼1.4 Hz, 1H,
H-3), 4.42 (dd, J¼8.0 Hz, J¼1.6 Hz, 1H, H-2), 7.84 ppm
(s, 1H, –NHNH2); 13C NMR (CDCl3, 50 MHz): d 25.14,
26.66 (–C(CH3)2), 26.82, 27.02 (–C(CH3)2), 67.71 (C-6),
69.87 (C-5), 76.89 (C-4), 76.94 (C-3), 79.72 (C-2), 109.91,
110.07 (2ꢁ–C(CH3)2), 171.75 ppm (–CO–NH–). Anal.
Calcd for C12H22N2O6: C, 49.65; H, 7.64; N, 9.65. Found:
C, 48.86; H, 7.77; N, 9.53.
References and notes
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4.1.22. 3,4,5,6-Di-O-isopropylidene-D-gluconic salicyl-
idene hydrazide (23). Procedure like that of 5. The product
was washed with ethanol. The conversion of 1.14 g
(4.0 mmol) 22 gave 1.12 g (70%) 23.
6. Brink, H. B.; Schoemaker, H. E.; Wever, R. Eur. J. Biochem.
2001, 268, 132–138.
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2640–2642.
1H NMR (DMSO-d6, 200 MHz): d 1.28, 1.35 (2s, 12H, 2ꢁ
–C(CH3)2), 3.80–3.86 (m, 1H), 3.95–4.19 (m, 3H, H-6, H-5,
H-4), 4.16 (s, 1H, H-3), 4.31 (dd, J¼7.6 Hz, J¼1.8 Hz,
1H, H-2), 6.08 (d, J¼6.4 Hz, 1H, –OH), 6.86–6.93 (m, 2H,
H-3Ar, H-5Ar), 7.24–7.32 (m, 1H, H-4Ar), 7.39–7.44
(m, 1H, H-6Ar), 8.67 (s, 1H, –CH]N–), 11.34 (s, 1H,
Ar–OH), 11.59 ppm (s, 1H, –CO–NH–); 13C NMR
(DMSO-d6, 50 MHz): d 25.25, 26.48 (–C(CH3)2), 26.74,
27.06 (–C(CH3)2), 66.59 (C-6), 69.90 (C-5), 75.1 (C-4),
76.45 (C-3), 80.32 (C-2), 108.91, 109.07 (2ꢁ–C(CH3)2),
116.41 (C-3Ar), 118.44 (C-1Ar), 119.29 (C-5Ar), 129.83
(C-6Ar), 131.32 (C-4Ar), 149.12 (–CH]N–), 157.50
(C-2Ar), 168.16 ppm (–CO–NH–). Anal. Calcd for
C19H26N2O7: C, 57.86; H, 6.64; N, 7.10. Found: C, 57.98;
H, 6.59; N, 7.13.
14. Wegner, R.; Gottschaldt, M.; Gorls, H.; Jager, E.-G.; Klemm,
¨
D. Angew. Chem., Int. Ed. 2000, 39, 595–599.
¨
15. Wegner, R.; Gottschaldt, M.; Gorls, H.; Jager, E.-G.; Klemm,
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¨
16. Wegner, R.; Gottschaldt, M.; Poppitz, W.; Jager, E.-G.;
¨
Klemm, D. J. Mol. Catal. A: Chem. 2003, 201, 93–118.
4.1.23. Potassium [1,2,3,4-tetra-O-methyl-a-D-glucopyr-
anuronic acid salicylidene hydrazidato] dioxo vanadate
(24). KVO3 0.190 g (1.36 mmol) was added to a solution
of 0.500 g (1.36 mmol) 20 in 75 ml methanol. The mixture
was refluxed for 24 h and filtered hot. After removing the
solvent the solid residue was washed with CH2Cl2. Yield:
0.42 g (63%) of a yellow powder.
17. Gottschaldt, M.; Wegner, R.; Gorls, H.; Klufers, P.; Jager,
¨
¨ ¨
E.-G.; Klemm, D. Carbohydr. Res. 2004, 339, 1941–1952.
18. Yan, S.; Klemm, D. Tetrahedron 2002, 58, 10065–10071.
´
`
19. Dieguez, M.; Pamies, O.; Claver, C. Chem. Rev. 2004, 104,
3189–3215.
´
`
´
´
20. Dieguez, M.; Pamies, O.; Ruiz, A.; Dıaz, Y.; Castillon, S.;
Claver, C. Coord. Chem. Rev. 2004, 248, 2165–2192.
21. Borriello, C.; Del Litto, R.; Panunzi, A.; Ruffo, F. Tetrahedron:
Asymmetry 2004, 15, 681–686.
MS (Micro-ESI neg. in MeOH): m/z¼937 (18%, 2(VO2L)ꢀ+
K+), 921 (20%, 2(VO2L)ꢀ+Na+), 449.3 (100%, (VO2L)ꢀ);
FTIR (KBr): 2939 (nas C–H –CH3), 2839 (nC–H –OCH3),
1617 (nC]N–N]C), 1570+1546 (nC]C Ar), 1476+1449
(das C–H –CH3), 1356+1362 (dsy C–H –CH3), 1157+1093+
22. Fridgen, J.; Herrmann, A. W.; Eickerling, G.; Santos, A. M.;
Kuhn, F. E. J. Organomet. Chem. 2004, 689, 2752–2761.
¨
23. Zhao, J.; Zhou, X.; Santos, A. M.; Herdtweck, E.; Romao,
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¨
3736–3742.
1071+1045 (nas C–O–C), 918+910 (nVO ), 760 cmꢀ1 (gOOP
2
amide); UV–vis (MeOH): lmax (log 3)¼228 (3.19), 290
24. Jansat, S.; Gomez, M.; Philippot, K.; Muller, G.; Guiu, E.;
Claver, C.; Castillon, S.; Chaudret, B. J. Am. Chem. Soc.
2004, 126, 1592–1593.
25. Guimet, E.; Dieguez, M.; Ruiz, A.; Claver, C. Tetrahedron:
Asymmetry 2005, 16, 2161–2165.
26. Flores-Santos, L.; Martin, E.; Aghmiz, A.; Dieguez, M.;
Claver, C.; Masdeu-Bulto, A.; Munoz-Hernandez, M. Eur. J.
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435–443.
1
(3.07), 381 (2.63) nm; H NMR (methanol-d3, 400 MHz):
d 3.38–3.57 (m, 3H, H-2, H-3, H-4), 3.38, 3.39, 3.44, 3.54
(4s, 12H, 4ꢁ–OCH3), 4.13 (d, J¼9.65 Hz, 1H, H-5), 4.90
(d, J¼3.36 Hz, 1H, H-1), 6.84–6.91 (m, 2H, H-3Ar, H-5Ar),
7.38–7.41 (m, 1H, H-4Ar), 7.49 (dd, J¼7.60 Hz,
J¼1.60 Hz, 1H, H-6Ar), 8.79 ppm (s, 1H, –CH]N–); 13C
NMR (methanol-d3, 100 MHz): d 55.65, 58.78, 60.65,
60.90 (4ꢁ–OCH3), 70.25 (C-5), 82.14 (C-3), 82.53 (C-2),
83.70 (C-4), 99.03 (C-1), 119.48 (C-3Ar), 120.15 (C-1Ar),
120.74 (C-5Ar), 133.76 (C-6Ar), 135.40 (C-4Ar), 158.83
(–CH]N–), 165.74 (C-2Ar), 173.31 ppm (–CO–N–);
28. Rajak, K. K.; Rath, S. P.; Mondal, S.; Chakravorty, A. J. Chem.
Soc., Dalton Trans. 1999, 2537–2540.

J. Becher et al. / Tetrahedron 62 (2006) 5675–5681
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