Synthesis and characterization of poly-O-methyl-[n]-polyurethane from a d-glucamine-based monomer

Article abstract of DOI:10.1016/j.carres.2011.02.022

Aminoalditol 1-amino-1-deoxy-d-sorbitol (1) was readily converted into 2,3,4,5-tetra-O-methyl derivative 5, a key precursor of a sugar-based [n]-polyurethane. For the polymerization, the free amino or primary hydroxyl groups of 5 were selectively activate

Full text of DOI:10.1016/j.carres.2011.02.022

Carbohydrate Research 346 (2011) 1398–1405
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Synthesis and characterization of poly-O-methyl-[n]-polyurethane
from a D-glucamine-based monomer
⇑
Adriana A. Kolender, Silvina M. Arce, Oscar Varela
CIHIDECAR-CONICET, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2,
Ciudad Universitaria, 1428 Buenos Aires, Argentina
a r t i c l e i n f o
a b s t r a c t
Article history:
Aminoalditol 1-amino-1-deoxy-D-sorbitol (1) was readily converted into 2,3,4,5-tetra-O-methyl deriva-
Received 17 January 2011
Received in revised form 22 February 2011
Accepted 24 February 2011
Available online 10 March 2011
tive 5, a key precursor of a sugar-based [n]-polyurethane. For the polymerization, the free amino or pri-
mary hydroxyl groups of 5 were selectively activated and employed as starting monomers in two
alternative procedures. Thus, the amino function of 5 was converted into the isocyanate derivative by
treatment with di-tert-butyltricarbonate, and polymerized in situ in the presence of Zr(IV) acetylaceto-
nate. The resulting poly(1-amino-1-deoxy-2,3,4,5-tetra-O-methyl-D-sorbitol)urethane (8) had a moder-
ate molecular weight and showed the presence of urea units. The alternative synthesis of 8 involved
the activation of the free hydroxyl group of 5 as the corresponding phenylcarbonate. The polymerization
Dedicated to Professor Dr. András Lipták on
the occasion of his 75th birthday
of this
a-amino-x-phenylcarbonate alditol monomer does not require a metal catalyst. The resulting
Keywords:
material exhibited an improved molecular weight and higher purity than that obtained via the isocya-
nate. [n]-polyurethane 8 was highly soluble in water as well as in common organic solvents (chloroform,
acetone, ethyl acetate, etc) and was obtained as an amorphous material which was characterized ther-
mally and spectroscopically.
[n]-Polyurethane
Chiral
Biomaterial
D
-Glucamine
Alditol isocyanate
-Amino- -phenylcarbonate
Ó 2011 Elsevier Ltd. All rights reserved.
a
x
1. Introduction
synthesis of their AB-type analogues ([n]-polyurethanes). Thus,
Thiem21 described the synthesis of a carbohydrate-derived [n]-
The design of new polymers with enhanced hydrophilicity and
biodegradability starting from carbohydrate-derived monomers
has attracted considerable attention.1–5 Carbohydrates are massive
renewable resources able to provide monomers suitable for the
synthesis of polycondensates. The inclusion of hydrophilic mono-
mers into the polymer chain facilitates water attack, increasing
the hydrolytic degradation of the material. Among the condensa-
tion polymers, a fair number of biobased polyurethanes and their
composites have been prepared from many natural resources.6
Sugar-based [m,n]-polyurethanes have been synthesized using
selectively protected derivatives of hexoses,7,8 aldaro9 and aldono-
lactones,10 alditols, 11–14 or anhydroalditols,15,16 as diol monomers.
Such diols have been polymerized with diisocyanate monomers to
afford the corresponding [m,n]-polyurethanes. These polymers
polyurethane by polycondensation of 2-deoxy-1,4:3,6-dianhydro-
2-isocyanato- -iditol obtained from 1,4:3,6-dianhydrosorbitol
L
using the toxic phosgene for conversion of the amino group
into isocyanate. Recently, we have reported the synthesis of an
unprotected polyhydroxy [n]-polyurethane from a 1-amino-1-
deoxyalditol precursor(1-amino-1-deoxy-2,3:4,5-di-O-isopropyli-
dene-D-galactitol) prepared from D
-galactono-1,4-lactone.22 In this
case, the amino group was converted into the isocyanate under the
mild conditions reported by Meijer and co-workers.23 for aliphatic
a,x
-aminoalkanols.
Here we describe, as an additional example, the synthesis of a
polyhydroxy [n]-polyurethane having the hydroxyl groups substi-
tuted as methyl ethers. The 1-amino-1-deoxy alditol monomer 5,
precursor of the polymer, was prepared through a short route from
have also been prepared by alternative procedures from
D
-glyco-
commercially available D-glucamine.
sylamines and D
-glucosamine,17 from dichloroformates of anhy-
drohexitols18 or from carbonate derivatives of
galactitol.20
D
-mannitol19 and
2. Results and discussion
In contrast to the rather numerous reports on sugar-based
For the synthesis of the aminoalditol monomer, the amino and
[m,n]-polyurethanes, there are just
a few examples on the
primary hydroxyl groups of
-sorbitol, 1) were protected by selective substitution with trityl
chloride (Scheme 1). The resulting N,O-ditrityl derivative
was treated with powdered NaOH in Me2SO and MeI for the
D-glucamine (1-amino-1-deoxy-
D
2
⇑
Corresponding author. Tel./fax: +54 11 4576 3352.
E-mail address: varela@qo.fcen.uba.ar (O. Varela).
0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.02.022

A. A. Kolender et al. / Carbohydrate Research 346 (2011) 1398–1405
1399
OH OH
OH OH
TrCl
NaOH, MeI
Me2SO
NHTr
NH2
HO
TrO
Et3N
OH OH
OH OH
1
2
Tr = Ph3C
(61%)
OMe OMe
OMe OMe
F3CCOH,
CH2Cl2
NRTr
NHR
TrO
HO
OMe
OMe
OMe
OMe
3
4
R = H (64%)
R = Me
5 R = H (95%)
6 R = Boc (COOBut) (99%)
(Boc)2O,
MeCN
Scheme 1. Synthesis of monomer 5 and its N-Boc derivative 6.
derivatization of the secondary alcohol functions as methyl ethers.
This reaction afforded, together with the expected tetra-O-methyl
derivative 3, the N-methyl compound 4, formed by additional
methylation of the amine. The structure of 4 was readily estab-
lished as the 1H NMR spectrum showed the resonance of the
N-methyl protons at 2.52 ppm. The signal of the N-methyl group
was also detected at 44.1 ppm in the 13C NMR spectrum of 4, and
the resonance of the methylene carbon of glucamine bonded to
nitrogen underwent a strong deshielding compared with the same
signal in 3, due to N-methylation.24
Removal of the N- and O-trityl groups of 3 by acid hydrolysis
with trifluoroacetic acid (TFA) afforded the aminoalditol 5. To re-
lease the amine from the trifluoroacetic salt, the product was
passed through a column filled with Amberlist A-26 (OHꢀ) ion-
exchange resin. The signals of H-2–H-4 in the 1H NMR spectrum
extended form.25 These results are relevant to explain the behavior
of 5 during the polymerization, as discussed later.
Aminoalditol
5 was treated with di-tert-butyltricarbonate
(DTBTC) for the conversion of the amino group into isocyanate 7
(Scheme 2). The DTBTC reagent was prepared as previously re-
ported.27 The crude isocyanate was employed for the polymeriza-
tion without isolation or purification.22,23 However, to confirm
the formation of 7, the FTIR spectrum of the mixture was recorded.
As expected, a strong band of the isocyanate group was observed at
2263 cmꢀ1. For the polymerization of 7, CHCl3 or THF was em-
ployed as solvent and the reaction was conducted in the presence
of one of the catalysts listed in Table 1.
The reaction mixture of polymerization was concentrated and
the polymeric material was isolated by dissolution in 2-propanol
and precipitation with hexane. This operation was repeated twice,
and the resulting product was dried and analyzed using FTIR,
NMR and, in some selected cases, MALDI-MS and gel permeation
chromatography (GPC). In general, polymer 8 was accompanied
by one or two by-products. For example, the 1H NMR spectrum
(recorded in CDCl3) of the polymeric material obtained in the Sn(ii)
2-ethylhexanoate (Sn(oct)2)-polycondensation of 5 in THF (entry 3
of Table 1) showed clearly the signals of the methylene group
bonded to oxygen in polyurethane 8 (4.08 and 4.51 ppm), together
with a pair of down-field signals (4.68 and 4.23 ppm), which were
attributed to cyclic oligomers (10). The spectrum exhibited also
signals at higher field (3.85 and 3.66 ppm) due to the hydroxy-
methyl groups of the urea derivative 9. The 13C NMR spectrum con-
firmed these assignments, as it showed in the region of the
of
5 collapsed into a complex multiplet between 3.30 and
3.65 ppm. However, the spectrum recorded in pyridine-d5 admit-
ted a first order analysis (Fig. 1). The coupling constant value
between H-2 and H-3 was higher than that expected for J2,3 in
the planar zig-zag conformation of the backbone chain of 5, and
was indicative of the contribution of a sickle form (2Gꢀ) to the con-
formational equilibrium.25 It is known that open-chain derivatives
of glucose or sorbitol usually adopt sickle forms by rotation of the
C-2–C-3 and/or C-3–C-4 bonds, in order to escape from the
1,3-parallel interaction between O-2–O-4 that occurs in the planar
conformation.26 Also, the small values for J5,6a and J5,6b (3.0 and
4.4 Hz, respectively) suggest that there is a substantial population
of a rotamer through the C-5–C-6 bond (5G+) instead of the fully
carbonyl group only two signals,
a broad one (major) at
156.5 ppm (urethane) and the other at 158.9 ppm (urea). These
values are in agreement with those reported for analogous poly-
mers.22,28 In addition, the FTIR spectrum showed characteristic
absorptions for the urethane (1733 and 1554 cmꢀ1) and urea
(1660 cmꢀ1) carbonyl groups. The GPC analysis of the product indi-
cated that we were dealing with a polydisperse material. Three
main peaks were detected corresponding to Mw = 2280, 740, and
540, values consistent with the presence of polymer 8, cyclic trimer
10 (n = 2), and urea 9, respectively.
To confirm these results, the material was applied to a silica gel
column which was eluted with 4:1 EtOAc–MeOH. Two fractions
were isolated and analyzed by MALDI-MS. In these spectra the dif-
ference of m/z values between peaks was 263, in accordance with
the repeating unit of the polymers. The fraction that eluted first
from the column showed at lower m/z values (400–1400) two sets
of signals, corresponding to [M+H]+ ions of linear and cyclic oligo-
mers. The most intense signal corresponded to the cyclic trimer. At
higher m/z values (above 1500) the spectrum was rather complex
4.3 4.2 4.1 4.0 3.9 3.8 3.7 3.6 3.5 3.4 3.3 3.2 3.1 3.0 2.9
ppm
Figure 1. 1H NMR spectrum of monomer 5 (C5D5N).

1400
A. A. Kolender et al. / Carbohydrate Research 346 (2011) 1398–1405
OMe OMe
OMe OMe
catalyst,
DTBTC
THF
NCO
NH2
HO
HO
solvent
OMe
OMe
OMe
OMe
5
7
OMe OMe
HN
O
O
OMe OMe
OMe OMe
O
OMe OMe
OMe OMe
O
OMe OMe
O
NH
OH
HO
n
+
+
O
N
N
H
H
O
OMe
OMe OMe
OMe OMe
NH
OMe
n
OMe OMe
8
9
10
Scheme 2. Polymerization of 5 via isocyanate derivative 7.
Table 1
[M+Na]+
Conditions employed for the polymerization of 5 via 7
No. Catalyst
(mol %)
Solvent Concentration Initiator Product distribution
of 7 (M)
8:9:10
1
2
3
4
5
6
7
Zr(acac)4 (0.5) CHCl3
Et3N (3.0) THF
1.0
0.8
1.0
0.4
0.4
0.4
0.7
No
No
No
No
No
Yes
Yes
10:90:0
23:77:0
[M+H]+
Sn(oct)2 (1.5) THF
Zr(acac)4 (0.1) THF
Zr(acac)4 (1.0) THF
Zr(acac)4 (1.0) THF
Zr(acac)4 (1.0) THF
55:18:27
50:40:10
66:21:13
64:36:0
83:17:0
1000
1500
2000
2500
3000
m/z
3500
4000
4500
5000
due to the contribution of ions of the oligomeric species with dif-
ferent terminal groups. The spectrum showed series of ions with
m/z values consistent with [M+H]+ (1554, 1817, 2080, 2343) and
[M+Na]+ (1576, 1839, 2103, 2365) corresponding to linear oligo-
mers, and [M+Na]+ ions due to cyclic oligomers (1602, 1865,
2128). Overlapped with these series, other ions were also observed
having m/z values separated by 263 mass units (1676, 1939, 2203,
2465). They were assigned to [M+Na]+ open-chain oligomers with
the terminal amino group substituted as tert-butyl carbamate.
These urethanes could be formed by reaction of the free amino
group of oligomers with the remaining DTBTC, which had been
employed for the in situ preparation of isocyanate 7. The heteroge-
neity of this fraction was reflected in the complexity observed in
the corresponding 1H and 13C NMR spectra. In these spectra,
signals were detected at 1.45 and 28.4 ppm, respectively, in agree-
ment with the presence of the methyl groups of tert-butoxycar-
bonyl. This fact supports its inclusion as a substituent of some
oligomers, as proposed in the terminal group analysis by MALDI-
MS.
The MALDI-MS of the fraction that eluted later from the column
showed signals due to [M+H]+ and [M+Na]+ ions. The most intense
peaks indicated that the polyurethane contained from 5 to 20
repeating units (Fig. 2). With the data obtained from the spectrum,
the Mw (2450) and Mn (2280) values were determined. The Mw
value was coincident with the one estimated by GPC.
The ratio between linear and cyclic urethanes (8 and 10, respec-
tively) and urea (9) in each individual preparation, shown in Table
1, was determined by integration of the CH2O signals from the 1H
NMR spectrum of the material precipitated from 2-propanol–
hexane, as explained above. The polymerization of 7 in CHCl3 (even
under optimized conditions) led to urea 9 as the major component
(entry 1). Similarly, the use of Et3N as catalyst (entry 2) was not
suitable, since the urea derivative 9 was mostly produced. Urea
linkages are expected to be formed by nucleophilic attack of the
amine of 5 to the isocyanate function of 7. The amine end-group
Figure 2. MALDI-MS of polyurethane 8, obtained from 7.
of 5 may be regenerated from 7 by hydrolysis of the isocyanato
group. As Et3N is not an efficient catalyst for the polycondensation,
compound 7 remains in the polymerization medium for a long
time (it was even detected after 10 h), increasing the possibility
of hydrolysis and concomitant urea formation. The 1H NMR spec-
trum of 9 recorded in pyridine-d5 allowed the assignment of the
signals, and particularly those of H-6a, H-6b, H-1a, H-1b and that
of NH. The integral of all of them were of equal magnitude (ratio
1:1:1:1:1) confirming the proposed structure for 9. Furthermore,
the MALDI-MS of 9 showed, as expected, the pseudomolecular ions
[M+H]+ and [M+Na]+ at m/z 501.3 and 523.3, respectively.
The polycondensation of 7 in THF, and in the presence of Zr(IV)
acetylacetonate (Zr(acac)4; 2,4-pentanedione Zr(IV) complex) as
catalyst, afforded the linear polymer 8 as the major product (en-
tries 4–7). The proportion of 8 increased with the increment in
the concentration of the catalyst (entries 4 and 5) although, in turn,
this might result in a lowering of the molecular weight of the poly-
mer.23 The formation of cyclic oligomers of low molecular weight
(monomer to tetramer) could be explained taking into account
the high flexibility of the monomer backbone chain, mentioned
above. In contrast, no cyclic oligomers were observed in the anal-
ogous polymerization of 2,3:4,5-di-O-isopropylidene-D-galacti-
tol,22 which adopts in solution the planar zig-zag conformation
with the diacetonide rings S-trans disposed. This arrangement
would facilitate the linear elongation of the polymer chain. The for-
mation of cyclic oligomers (10) could be prevented employing the
N-Boc derivative 6 as the initiator of the polymerization. However,
in all cases, and even under optimized conditions (entry 7), urea 9
was always the accompanying by-product of polyurethane 8.
This contaminant could not be eliminated even though many

A. A. Kolender et al. / Carbohydrate Research 346 (2011) 1398–1405
1401
procedures for the purification were attempted. The remaining
urea 9 (ꢁ10%) may be associated to the polymer by intermolecular
interactions. However, some urea units could be incorporated into
the polymer chain, as reported for analogous preparations of
[n]-polyurethanes from isocyanate alcohols.22,23 In view of these
results, we decided to conduct the synthesis of polyurethane 8
by an alternative route.
We have recently described a procedure for the synthesis of
common [n]-polyurethanes which takes place under smooth con-
ditions and does not require the use of metal catalysts.29 This pro-
cedure, applied to amino alditol 5, is illustrated in Scheme 3. The
amino function of monomer 5 was selectively protected as the
N-Boc derivative 6, which had been used in the previous method-
ology as the initiator of the polymerization. The free hydroxyl
group of 6 was activated for the polycondensation as the phenyl-
carbonate derivative 11, which was prepared by the treatment of
6 with phenyl chloroformate.
of polymerization (14) compared with those obtained in DMF
(1.85 and 7, respectively). The FTIR spectrum of 8 showed the
characteristic absorptions of the urethane NH (3366 cmꢀ1) and
carbonyl groups (1733 and 1546 cmꢀ1), whereas the peak of the
urea carbonyl (1660 cmꢀ1) was absent. In agreement with this
result, no urea signals were detected in the NMR spectra of 8
(Fig. 3). However, low intensity signals corresponding to the termi-
nal phenylcarbonate group of polyurethane 8 were observed. From
the integral of the signals of the aromatic and CH2OCO2 protons,
the Mn value (4210) was determined, which was consistent with
the molecular weight measured using GPC (Fig. 4). Polyurethane
8 behaves as an amorphous material as analyzed by differential
scanning calorimetry (DSC) that showed no thermal transitions
during the first heating cycle, followed by cooling and a second
heating process. The thermogravimetric analysis (TGA) for 8
indicated that the decomposition starts at 110 °C (Fig. 5). The
differential curves showed two main peaks at 165.1 and 281.2 °C
indicative of the decomposition in two steps.
The 1H NMR spectrum of 11 showed the expected deshielding
of the signals of the methylene protons vicinal to the carbonate
group (>0.6 ppm) compared to those of the hydroxymethyl group
in 6. Removal of the N-protecting tert-butoxycarbonyl group in
11 with a saturated solution of HCl in EtOAc afforded the hydro-
chloride derivative 12, as the conveniently activated monomer pre-
cursor of 8.
The amine function of 12 may be readily released from the
hydrochloride with an organic base. Therefore, the polymerization
of 12 was conducted in DMF or THF, and in the presence of
N,N-diisopropylethylamine (DIPEA). The polymerization is
expected to proceed by a nucleophilic attack of the amine to the
terminal phenylcarbonate with elimination of the phenyloxy as a
good leaving group.20,30 For the polycondensation, the volume of
the solution was adjusted to give a 1 M final concentration of 12,
and the mixture was stirred, under argon atmosphere, at 40 °C
for 3 days (Table 2). Polymer 8 was recovered and purified as for
the polymerization of 7, described above. The polyurethane was
released from the accompanying rests of DIPEA hydrochloride by
deionization with resin.
In summary, the synthesis of chiral, enantiomerically pure
[n]-polyurethane having four stereocenters in the repeating
unit has been accomplished by two alternative procedures. The
starting monomer, 1-amino-1-deoxy-2,3,4,5-tetra-O-methyl-
D-
sorbitol was readily prepared form -glucamine. In the first in-
D
stance, the amino function of the monomer was converted into
the reactive isocyanate group with di-tert-butyltricarbonate and
polymerized in situ. The resulting polymeric material contained
the desired linear [n]-polyurethane accompanied by cyclic oligo-
mers and a N,N0-disubstituted urea derivative as by-products.
Under optimized conditions, and after laborious purification, the
[n]-polyurethane was obtained as a material of moderate molecu-
lar weight, which showed contamination and possible incorpora-
tion of urea units into the polymer chain. In the alternative
synthesis of the [n]-polyurethane, the free hydroxyl group of the
starting monomer was activated for the polycondensation as the
a-amino-x-phenylcarbonate derivative. In this case, the polymer-
ization took place by a nucleophilic attack of the amine (released
from its hydrochloride) to the carbonate with the elimination of
phenol, and no metal catalyst was required. The polycondensation
conducted in THF as solvent and in the presence of DIPEA afforded,
after purification, a polymer that exhibited higher molecular
A higher molecular weight of 8 was obtained when THF, instead
of DMF, was employed as a solvent for the polymerization. This
material showed smaller polydispersity (1.37) and higher degree
OMe OMe
OMe OMe
PhOCOCl
NHBoc
O
H
N
HCl
O
PhO
HO
O
EtOAc
(98%)
C5H5N
OMe
OMe
OMe
O
OMe
(72% from 5)
6
11
OMe OMe
OMe OMe
O
DIPEA
H
N
NH2.HCl
O
PhO
O
THF
(81%)
OMe
OMe
O
OMe
OMe
n
12
Scheme 3. Polymerization of 5 via the active carbonate 12.
8
Table 2
Conditions employed for the polymerization of 5 via 12
No.
Mmol of 12
Solvent (mL)
DIPEA (mL)
Yield of 8 (%)
Mw
Mn
Mw/Mn
1
2
0.262
0.472
DMF (0.20)
THF (0.23)
0.10
0.24
64
81
3620
5210
1960
3800
1.85
1.37

1402
A. A. Kolender et al. / Carbohydrate Research 346 (2011) 1398–1405
7.30
4.73
4.30
7.4 7.2 7.0 6.8 6.6
6.2 6.0 5.8 5.6 5.4 5.2 5.0 4.8 4.6 4.4 4.2 4.0 3.8 3.6 3.4 3.2 3.0 2.8 2.6
6.4
ppm
Figure 3. 1H NMR spectrum of polyurethane 8 (CDCl3). Superimposed are the signals of the carbonate (RCH2OCO2Ph) terminal group.
Figure 4. Gel permeation chromatography (GPC) analysis for polyurethane 8.
Figure 5. Thermogravimetric analysis for polyurethane 8.

A. A. Kolender et al. / Carbohydrate Research 346 (2011) 1398–1405
1403
weight and higher purity than those of the polyurethane obtained
in the previous preparation. Thus, the polymerization using the
O-phenylcarbonate as active monomer seems to be more conve-
mixture was stirred at rt for 30 min and, upon cooling in an ice
bath, MeI (3.10 mL, 49.8 mmol) was added. After stirring for 1 h,
an additional amount of MeI (3.10 mL, 49.8 mmol) was added
and the stirring was continued for 1 h more. Water (50 mL) was
slowly incorporated into the mixture, which was then partitioned
between 1:1 CH2Cl2–H2O (200 mL). The aqueous layer was
extracted with CH2Cl2 (50 mL). The combined organic extracts
were dried (MgSO4) and concentrated. The residue was purified
by column chromatography (97:3 toluene–EtOAc). The first eluting
fractions from the column contained the desired compound 3,
impurified with N-methyl derivative 4 (0.97 g). Pure tetra-O-
methyl derivative 3 was isolated from the following fractions
nient for this particular aminoalditol which possesses the
configuration.
D-gluco
3. Experimental
3.1. General methods
1-Amino-1-deoxy-D-sorbitol was purchased from Aldrich
Chemical Company, Inc., and used as received. Analytical thin-layer
chromatography (TLC) was performed on Silica Gel 60 F254
(E. Merck) aluminum-supported plates (layer thickness 0.2 mm).
Visualization of the spots was effected by exposure to UV light or
by charring with a solution of 5% (v/v) sulfuric acid in EtOH,
containing 0.5% p-anisaldehyde. For unprotected amines, the plates
were heated after immersion in a solution of ninhydrin in acetone.
Column chromatography was carried out with Silica Gel 60
(230–400 mesh, E. Merck). Optical rotations were measured with
a Perkin–Elmer 343 digital polarimeter at 25 °C. Nuclear magnetic
resonance (NMR) spectra were recorded with a Bruker AMX 500 or
a Bruker AC 200 instrument, in CDCl3 solutions (tetramethylsilane
as an internal standard) unless otherwise indicated. The assign-
ments were assisted by 2D COSY, DEPT and HSQC techniques. IR
spectra (films) were recorded with a Nicolet 510P FT-IR spectrom-
eter. Gel permeation chromatography (GPC) was carried out using
Styragel columns (Waters), with THF as solvent at a flow rate of
1.0 mL/min. The calibration was performed using polystyrene
standards. Electron impact-mass spectra (EI-MS) were recorded
(1.93 g; 64%). Compound 3 gave ½a D25
ꢂ
= ꢀ12 (c 1.4, CHCl3); 1H
NMR (500 MHz, CDCl3) d 1.59 (br s, 1H, NH), 2.18 (dd, 1H, J1b,2
7.5, J1a,1b 12.3 Hz, H-1b), 2.49 (dd, 1H, J1a,2 2.9 Hz, H-1a), 2.99 (s,
3H, CH3O), 3.10 (dd, 1H, J5,6b 4.9, J6a,6b 10.3 Hz, H-6b), 3.30 (dd,
1H, J 2.0, 7.6 Hz, H-4), 3.46 (dd, 1H, dd, J5,6a 2.2 Hz, H-6a), 3.48,
3.50, 3.51 (3s, 3H each, CH3O), 3.46–3.50 (m, 2H, H-3, H-5), 3.67
(dt, 1H, J1b,2–J2,3 7.5 Hz, H-2), 7.18–7.54 (m, 30H, H-aromatic);
13C NMR (125.7 MHz, CDCl3) d 43.9 (C-1), 58.4, 59.2, 60.1, 60.4
(CH3O), 62.4 (C-6), 70.6 (Ph3CN), 79.6 (C-4), 80.6, 81.0 (C-3, C-5),
82.3 (C-2), 86.6 (Ph3CO), 126.2, 126.9, 127.7, 127.8, 128.7, 128.8,
144.1, 146.1 [(C6H5)3C]. Anal. Calcd for C44H43NO5: C, 79.86; H,
7.12; N, 1.94. Found: C, 79.64; H, 7.22; N, 2.06.
Compound 4: 1H NMR (200 MHz, CDCl3) d 2.42 (dd, 1H, J1b,2 7.6,
J1a,1b 12.4 Hz, H-1b), 2.52 (s, 3H, CH3N), 2.73 (dd, 1H,, J1a,2 3.0 Hz,
H-1a), 3.21 (s, 3H, CH3O), 3.31 (dd, 1H, J5,6b 5.1, J6a,6b 10.8 Hz,
H-6b), 3.66, 3.69, 3.70 (3s, 3H each, CH3O), 3.50–3.81 (m, 4H,
H-3–H-5, H-6a), 3.91 (ddd, 1H, J1b,2–J2,3 7.6 Hz, H-2), 7.22–7.81
(m, 30H, H-aromatic). 13C NMR (50.3 MHz, CDCl3) d 44.1 (CH3N),
58.2 (C-1), 58.6, 59.4, 60.4, 60.7 (CH3O), 62.5 (C-6), 70.8 (Ph3CN),
79.7 (C-4), 80.7, 81.2 (C-3, C-5), 82.5 (C-2), 86.8 (Ph3CO), 126.5,
127.2, 128.0, 128.1, 128.2, 128.9, 144.3, 146.3 [(C6H5)3C].
with
a Shimadzu QP5050A mass spectrometer, operating at
70 eV. MALDI-MS measurements were performed using a laser
desorption time-of-flight mass spectrometer Bruker Daltonics
OmniFlex. Dithranol (1,8,9-anthracenetriol) was used as the
matrix. High resolution mass spectrometry (HRMS-ESI) was per-
formed in a Bruker microTOF-Q II instrument. Thermogravimetric
analysis (TG) was performed in a Shimadzu TGA-51 apparatus;
samples of about 2 mg were heated at a rate of 10 °C/min. Differen-
tial scanning calorimetry (DSC) was conducted with a DSC Q20 TA
instrument. Samples of about 2 mg were heated from 50 to 200 °C
at a rate of 20 °C/min, then cooled at 5 °C/min to 50 °C (isothermic
5 min), and finally heated at 10 °C/min to 200 °C.
3.4. 1-Amino-1-deoxy-2,3,4,5-tetra-O-methyl-D-sorbitol (5)
A solution of compound 3 (0.58 g, 0.80 mmol) in anhydrous
CH2Cl2 (6.8 mL) was cooled in an ice bath and trifluoroacetic acid
(0.76 mL, 10.2 mmol) was slowly added. After 30 min, the mixture
was allowed to reach rt and it was stirred for additional 5 h. Upon
addition of MeOH (6 mL), the solution was concentrated. The resi-
due was partitioned between 1:1 H2O–toluene (50 mL). The organ-
ic layer was washed with water and the combined aqueous phases
were concentrated to ꢁ2 mL. The solution was passed through a
column filled with Amberlist A-26 (HOꢀ) ion-exchange resin to
3.2. 1-Deoxy-6-O-trityl-1-N-tritylamino-
D
-sorbitol (2)
give the aminoalditol 5 (0.176 g, 93%); ½a D25
ꢂ
= ꢀ30 (c 0.6, H2O);
To suspension of 1-amino-1-deoxy-
a
D-sorbitol (1, 1.0 g;
1H NMR (500 MHz, C5D5N) d 2.97 (dd, 1H, J1a,1b 13.2, J1b,2 6.5 Hz,
H-1b), 3.18 (dd, 1H, J1a,2 4.2 Hz, H-1a), 3.46, 3.48, 3.57, 3.58 (4s,
3H each, CH3O), 3.69 (ddd, 1H, J2,3 6.3 Hz, H-2), 3.72 (ddd, 1H, J4,5
6.4, J5,6a 3.0, J5,6b 4.4 Hz, H-5), 3.84 (dd, 1H, J3,4 3.8 Hz, H-3), 3.91
(dd, 1H, H-4), 4.04 (dd, 1H, J6a,6b 12.1 Hz, H-6b), 4.26 (1H, dd, H-
6a); 13C NMR (125.7 MHz, C5D5N) d 42.3 (C-1), 57.0, 58.4, 59.6
(CH3O), 59.8 (C-6), 60.3 (CH3O), 79.9 (C-4), 81.7 (C-3), 82.3 (C-5),
84.0 (C-2). ESI-HRMS: calcd for [C10H24NO5+H]+: 238.1649,
[C10H23NO5+Na]+: 260.1468. Found m/z: 238.1645 and 260.1461,
respectively.
5.5 mmol) in CH2Cl2 (20 mL) were added trityl chloride (4.0 g;
14.35 mmol) and Et3N (2.0 mL, 14.34 mmol). The mixture was stir-
red at room temperature (rt) for 3 days and then concentrated in
vacuo. The residue was purified by column chromatography (4:1
toluene–EtOAc) to give 2 (2.2 g; 61%) as a foam; ½a D25
= ꢀ3 (c 4.4,
ꢂ
CHCl3); 1H NMR (500 MHz, CDCl3 + D2O) d 2.44 (d, 2H, J 3.7 Hz,
CH2N), 3.30 (dd, 1H, J5,6b 6.0, J6a,6b 9.5 Hz, H-6b), 3.40 (dd, 1H,
J5,6a 6.0 Hz, H-6a), 3.76 (m, 3H, H-2–H-4), 3.93 (q, 1H, H-5), 7.15–
7.50 (m, 30H, H-aromatic); 13C NMR (50.3 MHz, CDCl3) d 47.0
(C-1), 64.8 (C-6), 70.6 (Ph3CN), 71.4 (C-5), 71.8, 72.4, 74.0
(C-2–C-4), 87.0 (Ph3CO), 126.6, 127.2, 127.9, 128.0, 128.5, 143.6,
145.1 (C6H5)3C. Anal. Calcd for C44H43NO5: C, 79.37; H, 6.51; N,
2.10. Found: C, 79.59; H, 6.76; N, 2.15.
3.5. 1-(N-tert-Butoxycarbonylamino)-1-deoxy-2,3,4,5-tetra-O-
methyl-D-sorbitol (6)
3.3. 1-Deoxy-2,3,4,5-tetra-O-methyl-6-O-trityl-1-N-tritylamino-
To a solution of compound 5 (0.132 g, 0.557 mmol) in CH3CN
(2 mL) were added Boc2O (0.260 mL, 1.11 mmol) and Et3N
(0.16 mL, 1.11 mmol). The mixture was stirred at rt for 16 h, and
then was concentrated to yield a syrup. Purification by column
chromatography (3:2 toluene–EtOAc) afforded pure 6 (0.186 g,
D
-sorbitol (3) and 1-deoxy-1-(N-methyl, N-tritylamino)-2,3,4,5-
tetra-O-methyl-6-O-trityl- -sorbitol (4)
D
To a stirred solution of compound 2 (2.80 g, 4.2 mmol) in Me2SO
(8 mL) was added finely powdered NaOH (3.2 g, 80 mmol). The
99%); ½a 2D5
ꢂ
= +1 (c 1, CHCl3); 1H NMR (500 MHz, CDCl3 + D2O) d

1404
A. A. Kolender et al. / Carbohydrate Research 346 (2011) 1398–1405
1.41 (s, 9H, C(CH3)3), 3.17 (dd, 1H, J1b,2 6.0, J1a,1b 14.0 Hz, H-1b),
3.31 (dt, 1H, J5,6a–J5,6b 3.7, J4,5 6.2 Hz, H-5), 3.26–3.56 (m, 5H,
H-1a, H-2–H-5), 3.39, 3.45, 3.48, 3.51 (4s, 3H each, CH3O), 3.67
(dd, 1H, J5,6b 3.7, J6a,6b 12.1 Hz, H-6b), 3.85 (dd, 1H, J5,6a 3.6 Hz,
H-6a), 5.01 (br s, 1H, NH); 13C NMR (125.7 MHz, CDCl3) d 28.3
(C(CH3)3), 40.5 (C-1), 57.1, 58.7 (CH3O), 59.5 (C-6), 60.3, 60.5
(CH3O), 79.0 (C-4), 79.2 (C(CH3)3), 79.7 (C-3), 81.0 (C-5), 81.5
(C-2), 156.0 (NCO2). ESI-HRMS: calcd for [C15H31NO7+Na]+:
360.1993. Found m/z: 360.2000.
CDCl3) d 28.4 ((CH3)3C), 40.7 (C-1), 57.8, 58.9, 60.4, 60.7 (CH3O),
66.4 (C-6), 71.9, 73.3, 79.8 (C-3–C-5), 79.3 ((CH3)3C), 81.5 (C-2),
121.0, 126.0, 129.5, 151.1 (C-aromatic), 153.7 (OCO2), 156.0
(NCO2). Anal. Calcd for C22H35NO9: C, 57.75; H, 7.71; N, 3.06.
Found: C, 57.49; H, 7.98; N, 3.50.
3.8. 1-Amino-1-deoxy-2,3,4,5-tetra-O-methyl-6-O-
phenyloxycarbonyl-D-sorbitol hydrochloride (12)
Compound 11 (0.264 g, 0.58 mmol) was dissolved in EtOAc sat-
urated with HCl (15 mL). The solution was stirred at rt for 20 h.
After concentration, the residue was washed with EtOAc
(3 ꢃ 4 mL) to give compound 12 (0.223 g, 98%); 1H NMR
(500 MHz, DMSO-d6) d 2.81 (m, 1H, H-1a), 3.04 (m, 1H, H-1b),
3.34, 3.38, 3.41, 3.43 (4s, 3H each, CH3O), 3.43 (m, 1H, H-4), 3.56
(dd, 1H, J3,4 3.1, J2,3 6.1 Hz, H-3), 3.59 (td, 1H, J5,6a 2.3, J4,5–J5,6b
5.7 Hz, H-5), 3.76 (ddd, 1H, J 2.9, J2,3 6.1, J 9.0 Hz, H-2), 4.19 (dd,
1H, J6a,6b 12.0 Hz, H-6b), 4.62 (dd, 1H, H-6a), 7.23–7.46 (m, 5H,
H-aromatic), 8.03 (br s, 3H, NH); 13C NMR (125.7 MHz, DMSO-d6)
d 39.2 (C-1), 57.4, 58.6, 59.3, 59.4 (CH3O), 66.9 (C-6), 76.9 (C-2),
78.0 (C-4), 78.6 (C-5), 79.2 (C-3), 121.3, 126.3, 129.7, 150.8 (C-aro-
matic), 153.1 (OCO2). Anal. Calcd for C17H27NO7ꢄ1.5HCl: C, 49.55;
H, 6.97; N, 3.40. Found: C, 49.44; H, 7.34; N, 3.39.
3.6. General procedure for the polymerization of 5 via
isocyanate 7
To a solution of 5 (0.066 g, 0.28 mmol) in THF (0.4 mL) was
added DTBTC27 (0.090 g, 0.34 mmol). The mixture was stirred at
rt, under a static argon atmosphere, for 2 h. In the first occasion,
a small portion was concentrated at rt in order to verify the conver-
sion of 5 into 1-deoxy-1-isocyanate-2,3,4,5-tetra-O-methyl-D-sor-
bitol (7): IR (KBr, film): 3407 (br, OH) and 2263 cmꢀ1 (s, NCO).
To a solution of crude 7 in CHCl3 or THF was added a solution of
the corresponding catalyst [Zr(acac)4, Sn(oct)2 or Et3N] in the same
solvent. When the polymerization was conducted in the presence
of the initiator 6, a solution of the catalyst and the initiator was
prepared and, after 1 h of stirring at rt, the monomer was added.
The final concentrations of monomer and reagents are shown in
Table 1. The polymerization was conducted under Ar atmosphere
at 40 °C for 16 h, with vigorous stirring. Then, it was concentrated
and the residue was redissolved in 2-propanol (0.3 mL). The poly-
mer was isolated by precipitation with hexane (3 mL). This proce-
dure was repeated twice. The results of the polymerization are
summarized in Table 1.
3.9. General procedure for the polymerization of 12
To a solution of 12 (0.2 g, 0.5 mmol) in DMF or THF (0.25 mL)
was added DIPEA (1.5 mmol). The volume of the solution was ad-
justed with the solvent to give 1 M solution of 12. The mixture
was stirred at 40 °C under Ar atmosphere for 3 days. Then, the
upper phase was removed and the lower one was concentrated.
The residue was dissolved in 2-propanol (0.2 mL) and precipitated
with hexane (4 mL). Polyurethane 8 (0.123 g, 99%) isolated by this
procedure was contaminated with DIPEA hydrochloride (according
to the 1H NMR spectrum). Therefore, this material was dissolved in
H2O and passed through a column containing Dowex MR-3C mixed
bed resin. The polymer recovered after this procedure was free of
the ammonium salt (0.107 g, 81%). The results of the polymeriza-
tion are summarized in Table 2. DSC: No thermal transitions were
observed after heating, cooling, and second heating cycles. TG:
From rt to 450 °C, 90% mass loss; the differential curve showed
two minimum peaks at 165.1 and 281.2 °C.
Polyurethane 8: ½a D25
= ꢀ2 (c 1.2, H2O); IR (film): 3366 (br, NH),
ꢂ
1733, 1546 cmꢀ1 (s, NCOO); 1H NMR (500 MHz, CDCl3) d 3.20 (m,
1H, H-1b), 3.41–3.60 (m, 5H, H-1a, H-2–H-5), 3.41, 3.48, 3.49,
3.53 (4s, 3H each, CH3O), 4.10 (d, 1H, J6a,6b 11.4 Hz, H-6b), 4.54
(d, 1H, H-6a), 5.41 (br s, 1H, NH). 13C NMR (125.7 MHz, CDCl3) d
41.6 (C-1), 57.4, 59.1, 60.3, 60.6 (CH3O), 61.9 (C-6), 78.8, 78.9,
79.9, 81.0 (C-2–C-5), 156.5 (CO).
N,N0-Disubstituted urea 9: ½a 2D5
ꢂ
= +2 (c 1.7, CHCl3); 1H NMR
(500 MHz, C5D5N) d 3.49, 3.51, 3.59 (3s, 3H each, CH3O), 3.65 (m,
1H, H-1b), 3.67 (s, 3H, CH3O), 3.75 (ddd, 1H, J4,5 6.1, J5,6a 3.2, J5,6b
4.6 Hz, H-5), 3.84 (dd, 1H, J2,3 6.3, J3,4 3.9 Hz, H-3), 3.94 (td, J1a,2
–
J2,3 6.3, J1b,2 4.2 Hz, H-2), 4.04 (dd, 1H, H-4), 4.07 (dd, 1H, J6a,6b
12.0 Hz, H-6b), 4.08 (m, 1H, H-1a), 4.29 (dd, 1H, H-6a), 6.82 (t,
1H, J 5.8 Hz, NH); 13C NMR (125.7 MHz, C5D5N) d 46.6 (C-1), 57.9,
59.2, 60.5 (CH3O), 60.7 (C-6), 60.9 (CH3O), 80.7 (C-4), 82.2 (C-2),
82.7 (C-3), 83.2 (C-5), 160.2 (CO). ESI-HRMS: calcd for
[C21H44N2O11+H]+: 501.3018; [C21H44N2O11+Na]+: 523.2837. Found
m/z: 501.3030 and 523.2856, respectively.
Acknowledgments
Support of this work by the University of Buenos Aires (Project
X227), the National Research Council of Argentina (CONICET, Pro-
ject PIP 2008-0064) and the National Agency for Promotion of Sci-
ence and Technology (ANPCyT, PICT 2007-00291) is gratefully
acknowledged. O.V. and A.A.K. are Research Members from
CONICET.
3.7. 1-(N-tert-Butoxycarbonylamino)-1-deoxy-2,3,4,5-tetra-O-
methyl-6-O-phenyloxycarbonyl-D-sorbitol (11)
References
Crude compound 6, obtained from 5 as described above, was
employed for the next reaction without further purification. After
concentration of the reaction mixture of preparation of 6, the res-
idue was dissolved in dry pyridine (1.2 mL), and phenylchlorofor-
mate (0.070 mL, 0.56 mmol) was added. The mixture was stirred
at rt for 24 h. After subsequent addition of MeOH and toluene,
the mixture was concentrated and purified by column chromatog-
raphy (4:1 toluene–EtOAc) to yield 12 (0.181 g, 72% from 5);
1. Van De Manakker, F.; Vermonden, T.; Van Nostrum, C. F.; Hennink, W. E.
Biomacromolecules 2009, 10, 3157–3175.
2. Satoh, T.; Kakuchi, T. Macromol. Biosci. 2007, 7, 999–1009.
3. Okada, M. Prog. Polym. Sci. 2002, 27, 87–133.
4. Varela, O.; Orgueira, H. A. Adv. Carbohydr. Chem. Biochem. 1999, 55, 137–174.
5. Galbis, J. A.; García-Martín, M. G. Top. Curr. Chem. 2010, 295, 147–176.
´
6. DwanIsa, J. P.; Mohanty, A. K.; Misra, M.; Drzal, L. T. Biobased Polyurethanes
and Their Composites: Present Status and Future Perspective In Mohanty, A. K.,
Misra, M., Drzal, L. T., Eds.; Natural Fibers, Biopolymers and Biocomposites; CRC
Press: Taylor and Francis, Boca Raton, 2005; pp 775–805.
½
a 2D5 = +3 (c 5, CHCl3); 1H NMR (500 MHz, CDCl3) d 1.45 (s, 9H,
ꢂ
7. Garçon, R.; Clerk, C.; Gesson, J.-P.; Bordado, J.; Nunes, T.; Caroço, S.; Gomes, P.
T.; Minas da Piedade, M. E.; Rauter, A. P. Carbohydr. Polym. 2001, 45, 123–127.
8. Hashimoto, K.; Yaginuma, K.; Nara, S.-I.; Okawa, H. Polymer J. 2005, 37, 384–390.
9. Hashimoto, K.; Wibullcksanakul, S.; Okada, M. J. Polym. Sci., Part A: Polym. Chem.
1995, 33, 1495–1503.
C(CH3)3), 3.21 (m, 1H, H-1b), 3.42 (m, 1H, H-2), 3.47, 3.49, 3.52,
3.55 (4s, 3H each, CH3O), 3.54–3.57 (m, 4H, H-1a, H-3–H-5), 4.30
(dd, 1H, J5,6a 4.5, J6a,6b 11.7 Hz, H-6b), 4.72 (d, 1H, H-6a), 4.97 (br
s, 1H, NH), 7.18–7.41 (m, 5H, H-aromatic); 13C NMR (125.7 MHz,

A. A. Kolender et al. / Carbohydrate Research 346 (2011) 1398–1405
1405
10. Yamanaka, C.; Hashimoto, K. J. Polym. Sci., Part A: Polym. Chem. 2002, 40, 4158–
4166.
21. Bachmann, F.; Reimer, J.; Ruppenstein, M.; Thiem, J. Macromol. Rapid Commun.
1998, 19, 21–26.
11. Paz, M. V.; Marín, R.; Zamora, F.; Hakkou, K.; Alla, A.; Galbis, J. A.; Muñoz-
Guerra, S. J. Polym. Sci., Part A: Polym. Chem. 2007, 45, 4109–4117.
12. Paz, M. V.; Aznar, J. A.; Galbis, J. A. J. Carbohydr. Chem. 2008, 27, 120–140.
13. Marín, R.; Muñoz-Guerra, S. J. Polym. Sci., Part A: Polym. Chem 2008, 46, 7996–
8012.
22. Gomez, R. V.; Varela, O. Macromolecules 2009, 42, 8112–8117.
23. Versteegen, R. M.; Sijbesma, R. P.; Meijer, E. W. Angew. Chem., Int. Ed. 1999, 38,
2917–2919.
24. Breitmaier, E.; Voelter, W. Carbon-13 NMR Spectroscopy, 3rd ed.; Weinheim:
Germany, 1987.
14. Marín, R.; Paz, M. V.; Ittobane, N.; Galbis, J. A.; Muñoz-Guerra, S. Macromol.
Chem. Phys. 2009, 210, 486–494.
15. Marín, R.; Muñoz-Guerra, S. J. Appl. Polym. Sci. 2009, 114, 3723–3736.
16. Braun, D.; Bergmann, M. Angew. Makromol. Chem. 1992, 199, 191–205.
17. Bachmann, F.; Ruppenstein, M.; Thiem, J. J. Polym. Sci., Part A: Polym. Chem.
2001, 39, 2332–2341.
18. Thiem, J.; Luders, H. Makromol. Chem. 1986, 187, 2775–2785.
19. Prömpers, G.; Keul, H.; Höcker, H. Des. Monomers Polym. 2005, 8, 547–569.
20. Prömpers, G.; Keul, H.; Höcker, H. Green Chem. 2006, 8, 467–478.
25. Blanc-Muesser, M.; Defaye, J.; Horton, D. Carbohydr. Res. 1980, 87, 71–86.
26. (a) Angyal, S. J. Carbohydr. Res. 1972, 23, 121–134; (b) Gillies, D. G.; Lewis, D. J.
Chem. Soc., Perkin Trans. 2 1985, 87, 1155–1159.
27. Pope, B. M.; Yamamoto, Y.; Tarbell, D. S. Org. Synth. 1978, 57, 45–50.
28. Rokicki, G.; Piotrowska, A. J. Polymer 2002, 43, 2927–2935.
29. Arce, S. M.; Kolender, A. A.; Varela, O. Polym. Int. 2010, 59, 1212–1220.
30. Neffgen, S.; Kušan, J.; Fey, T.; Keul, H.; Höcker, H. Macromol. Chem. Phys. 2000,
201, 2108–2114.