The reaction of penta-O-benzoyl-D-glucopyranose with piperidine: Characterization of the products isolated and study of the reaction mechanism

Article abstract of DOI:10.1016/S0008-6215(99)00029-4

The reaction of penta-O-benzoyl-D-glucopyranose with piperidine gave N-(2,3,6-tri-O-benzoyl-β-D-glucopyranosyl)piperidine (44.1%), N-(2,4,6-tri-O-benzoyl-β-D-glucopyranosyl)piperidine (1.5%), N-benzoylpiperidine and piperidinium benzoate (approx 1 mol of each of these two products per mol of substrate). When several penta-O-benzoyl-D-glucopyranoses containing selectively ¹⁴C-labeled benzoyloxy groups were submitted to the same reaction, it was found that N-benzoylpiperidine is formed at the expense of benzoyloxy-C-1, piperidinium benzoate arises mainly from benzoyloxy-C-2, and the benzoyloxy groups originally attached to C-3, C-4, and C-6 remain in the major product of the reaction. These results demonstrate that the first compound produced in the reaction is N-(3,4,6-tri-O-benzoyl-β-D-glucopyranosyl)piperidine, which could not be isolated because it undergoes two consecutive benzoyl migrations: a migration from O-3 to O-2 to give the 2,4,6-tri-O-benzoate, followed by a migration from O-4 to O-3 to afford the 2,3,6-tri-O-benzoate. A mechanism to explain the formation of piperidinium benzoate from benzoyloxy-C-2 of penta-O-benzoyl-D-glucopyranose is proposed. Copyright (C) 1999 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(99)00029-4

Carbohydrate Research 316 (1999) 34–46
The reaction of penta-O-benzoyl- -glucopyranose with
D
piperidine: characterization of the products isolated and
study of the reaction mechanism
Amelia E. Salinas *
Departamento de Qu´ımica Orga´nica, Facultad de Ciencias Exactas y Naturales, Uni6ersidad de Buenos Aires,
Pabello´n II, Ciudad Uni6ersitaria, 1428 Buenos Aires, Argentina
Received 6 July 1998; accepted 18 January 1999
Abstract
The reaction of penta-O-benzoyl-
osyl)piperidine (44.1%), N-(2,4,6-tri-O-benzoyl-b-
ridinium benzoate (approx 1 mol of each of these two products per mol of substrate). When several
penta-O-benzoyl-
-glucopyranoses containing selectively 14C-labeled benzoyloxy groups were submitted to the same
D
-glucopyranose with piperidine gave N-(2,3,6-tri-O-benzoyl-b-
D-glucopyran-
D
-glucopyranosyl)piperidine (1.5%), N-benzoylpiperidine and pipe-
D
reaction, it was found that N-benzoylpiperidine is formed at the expense of benzoyloxy-C-1, piperidinium benzoate
arises mainly from benzoyloxy-C-2, and the benzoyloxy groups originally attached to C-3, C-4, and C-6 remain in
the major product of the reaction. These results demonstrate that the first compound produced in the reaction is
N-(3,4,6-tri-O-benzoyl-b-D-glucopyranosyl)piperidine, which could not be isolated because it undergoes two consec-
utive benzoyl migrations: a migration from O-3 to O-2 to give the 2,4,6-tri-O-benzoate, followed by a migration from
O-4 to O-3 to afford the 2,3,6-tri-O-benzoate. A mechanism to explain the formation of piperidinium benzoate from
benzoyloxy-C-2 of penta-O-benzoyl-
D
-glucopyranose is proposed. © 1999 Elsevier Science Ltd. All rights reserved.
Keywords: Per-O-acylated-
ation; Acyl migration; Reaction mechanism
D
-glucopyranoses; Reaction with piperidine; N-(b-
D
-Glucopyranosyl)piperidine derivatives; O-Deacyl-
tri - O - acetyl - b -
D
- glucopyranosyl)piperidine
1. Introduction
(36%). They pointed out that optimum yields
were obtained using 3 mol of piperidine per
The reaction of penta-O-acetyl- -glucopy-
D
mol of penta-O-acetyl- -glucopyranose, since
D
ranose with piperidine was earlier studied by
Vogel [1]. Although no crystalline products
could be isolated, he concluded that O-de-
acetylation on C-1 and C-2 had occurred,
since his tests for enediol formation in the
reaction mixture were positive.
Some 15 years later, Hodge and Rist [2]
could isolate a crystalline compound from the
same reaction, and proved it to be N-(3,4,6-
N-acetylpiperidine and piperidinium acetate
were also formed.
When extended to octa-O-acetylcellobiose
[3], this reaction produced N-(3,6,2%,3%,4%,6%-
hexa-O-acetyl-b-cellobiosyl)piperidine. If the
reaction with piperidine was halted after a
short time [4], the major product was the
anomerically unsubstituted hepta-O-acetylcel-
lobiose having the a-
Apart from its use in the production of
2-O-substituted derivatives of -glucose [2,5]
D
configuration.
* Fax: +54-11-4576-3346.
D
0008-6215/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(99)00029-4

A.E. Salinas / Carbohydrate Research 20 (1999) 34–46
35
or cellobiose [3], the reaction of per-O-acetyl-
ated sugars with piperidine has received little
attention from carbohydrate chemists, and no
studies have been undertaken to elucidate the
mechanism of O-deacetylation at C-2 of the
sugar.
N-benzoylpiperidine and piperidinium ben-
zoate were also obtained, in yields respectively
corresponding to 1.02 and 0.90 mol/mol of
starting material. The amount of the latter
was estimated by measuring the benzoic acid
produced.
This paper describes the analogous reaction
between
penta-O-benzoyl- -glucopyranose
D
and piperidine which, unexpectedly, failed to
produce N-(3,4,6-tri-O-benzoyl-b- -glucopy-
D
ranosyl)piperidine and afforded an isomeric
tribenzoate as the major product. Neverthe-
less, the use of isotopic tracers revealed that
O-debenzoylation had occurred at C-1 and
C-2 of the substrate, and provided informa-
tion as to which of the benzoyloxy groups of
penta-O-benzoyl- -glucopyranose were in-
D
When submitted to acid hydrolysis, com-
pound 8 afforded 2,3,6-tri-O-benzoyl-a- -glu-
volved in formation of the isolated products.
D
copyranose (15) as the main product.
Benzoylation of 8 produced the perbenzoate
10. On acetylation, 8 afforded the tribenzoyl
monoacetyl derivative 11. The location of
benzoyloxy groups at C-2, C-3, and C-6 was
demonstrated by the 1H and 13C NMR spectra
of 8 (Tables 2 and 3), that were correlated
2. Results and discussion
The reaction of penta-O-benzoyl-b- -glu-
D
copyranose (1) with piperidine in ether for 6
days at room temperature (rt) afforded three
1
13
with the H and C NMR spectra of perbenz-
oate 10 and acetate 11 (Tables 4 and 5).
By acid hydrolysis, compound 9 produced
the already [8] described 2,4,6-tri-O-benzoyl-
benzoylated derivatives of N-(b- -glucopyran-
D
osyl)piperidine, which were isolated by chro-
matographic techniques and characterized by
chemical and spectroscopic procedures: N-
a- -glucopyranose (16) as the major product.
D
(2,3,6-tri-O-benzoyl-b-
peridine (8), N-(2,4,6-tri-O-benzoyl-b-
copyranosyl)piperidine (9), and N-(2,3,4,6-
D
-glucopyranosyl)pi-
The position of benzoyloxy groups at C-2,
C-4, and C-6 was confirmed by the 1H and 13C
NMR spectra of 9 (Tables 2 and 3), which
D-glu-
tetra - O - benzoyl - b -
D
- glucopyranosyl)-
1
were correlated with the H and 13C NMR
piperidine (10). The respective yields are indi-
spectra of perbenzoate 10 (Tables 4 and 5).
When compound 10 was submitted to acid
cated in Table 1. From the reaction mixture,
Table 1
hydrolysis,
2,3,4,6-tetra-O-benzoyl-a- -glu-
D
Products from the reaction of acylated
piperidine
D-glucopyranoses with
copyranose (17) [8,9] was isolated. The
anomeric configuration for compounds 8, 9,
10, 11, and 15 was assigned by H NMR
1
Substrate
Products (% yield)
spectroscopy, on the basis of the J1,2 value
[10]. The b-anomeric configuration obtained
8
9
10
12
13
14
for the N- -glucopyranosylpiperidines 8, 9,
D
1
44.1
53.7
52.7
1.5
2.3
1.8
0.5
1.2
and 10, and the preferred formation of a
anomers when these compounds were con-
17
18
7a
7b
verted into the
D-glucopyranoses 15, 16, and
33.2
1.8
4.1
0.5
0.3
17 may be rationalized on the basis of electro-
static and steric interactions. It is known that
electronegative substituents at the anomeric
carbon atom prefer to assume axial rather
than equatorial orientations, contrary to ex-
a The reaction was performed under crystallizing condi-
tions.
b The reaction was accomplished under homogeneous con-
ditions.

Table 2
1H NMR spectral data for N-(b-
D-glucopyranosyl)piperidine derivatives
Compound Chemical shifts (l, ppm)
H-1 (d)a H-2 (t) H-3 (t) H-4 (t)
H-5 (m)
3.71
H-6b (dd) H-6%b (dd) –N(CH2CH2)2CH2 –N(CH2CH2)2CH2 Ph
OH (bs) Oac (s)
8c
4.22
4.20
4.34
4.27
3.86
3.94
3.98
5.55
5.39
5.66
5.60
3.68
5.08
5.15
5.46
4.12
5.91
5.72
5.11
5.02
5.21
3.80
5.30
5.58
5.36
4.94
3.47
4.98
4.73
4.41
4.47
4.43
4.22
4.42
4.23
4.62
4.60
4.60
4.57
4.08
4.30
4.11
2.54–2.60
2.97–3.03
2.50–2.60
2.92–3.03
2.55–2.63
3.01–3.09
2.55–2.65
3.00–3.10
2.53–2.62
2.84–2.93
2.45–2.59
2.83–2.95
2.50–2.60
1.26–1.40
1.28–1.45
1.35–1.45
1.35–1.45
1.45–1.65
1.35–1.60
1.40–1.65
7.31–7.59 3.32d
7.91–8.10
7.35–7.60 2.80d
7.97–8.07
7.26–7.58
7.81–8.03
7.32–7.60
7.92–8.12
2.29d
9
3.91
10c
11
12c
13
14
4.03
3.90
1.92
/
3.59
2.02, 2.06, 2.07
2.03, 2.09, 2.10
3.40
2.65d
3.58
2.01, 2.02, 2.03,
2.08
2.85–2.97
Coupling constants (Hz)
2
(
b
b
b
J1,2
J2,3
J3,4
J4,5
J5,6
J5,6%
J6,6%
3
8c
9
8.8
9.3
9.2
8.9
9.1
8.7
8.8
9.4
9.2
9.3
9.4
9.2
9.1
9.1
9.6
9.3
9.6
9.5
9.5
9.3
9.4
9.0
9.2
9.7
9.6
9.7
9.3
9.8
3.9
5.2
4.9
4.8
4.8
3.9
4.7
2.3
3.1
3.4
2.7
2.6
1.9
2.6
−12.0
−11.9
−11.9
−12.1
−12.1
−12.1
−12.1
10c
11
12c
13
14
a Signal multiplicities are given in parentheses.
b The assignments of H-6 and H-6% are shown in Fig. 1.
1
c Signal assignments were confirmed by the two-dimensional H–1H chemical-shift correlated spectrum.
d Disappeared on deuteration.

A.E. Salinas / Carbohydrate Research 20 (1999) 34–46
37
pectations based on steric considerations
(anomeric effect). The magnitude of this effect
is dependent upon the electronegativity of the
substituent directly attached to C-1 [11]. Since
nitrogen is less electronegative than oxygen, in
N- -glucopyranosylpiperidines the anomeric
D
effect will be comparatively small and steric
effects that favor the formation of b anomers
will be preponderant.
When compound 17 was treated with piper-
idine in ether for 6 days at rt, compounds 8, 9,
and 10 were obtained (Table 1). The reaction
produced 0.89 mol of piperidinium benz-
oate (isolated as benzoic acid) per mol of
starting material, but only traces of N-benz-
oylpiperidine were detected by TLC. At the
beginning of the reaction, a 1:1 salt-like ad-
duct of 2,3,4,6-tetra-O-benzoyl- -glucopyran-
D
ose and piperidine (87.4%) crystallized sponta-
1
neously from the reaction mixture. The H
NMR spectrum of the adduct revealed a high
degree of hydrogen bonding between the ni-
trogen atom of piperidine and the oxygen
atom from C-1 of the tetrabenzoate. A similar
adduct of 2,3,4,6-tetra-O-acetyl- -glucopyran-
D
ose and benzylamine has been reported [12].
An interconversion between 8 and 9 was
observed when these compounds were sepa-
rately treated with piperidine in ether for 6
days at rt. In contrast, 10 was not altered
when it was submitted to the same treatment.
Since compounds 8 and 9 are formed from 17
and piperidine, but not from 10 and piper-
idine, it may be concluded that the O-debenz-
oylation must accompany or precede the for-
mation of the glucosylamine linkage.
When 3,4,6-tri-O-benzoyl-a- -glucopyran-
D
ose (18) [8] was treated with piperidine in
ether for 3 days at rt, compounds 8 and 9
were obtained (Table 1). This fact revealed
that two consecutive benzoyl migrations had
taken place during the reaction: a migration

38
A.E. Salinas / Carbohydrate Research 20 (1999) 34–46
Table 4
1H NMR chemical-shift correlations for compounds 8–14
Dl (ppm)a for indicated compounds
Atom
H-1
H-2
H-3
H-4
H-5
H-6b
H-6%b
10–8
11–8
10–9
14–12
14–13
+0.12
+0.05
+0.14
+0.12
+0.04
+0.11
+0.05
+0.27
+1.47c
+0.07
+0.45
+0.26
+1.79c
+0.10
+0.19
+1.78c
+1.56c
+0.28
+0.04
+1.51c
+0.32
+0.19
+0.12
−0.01
+0.18
−0.26d
−0.30d
+0.06
+0.01
−0.19d
−0.02d
−0.05d
0.00
+0.03
−0.19d
a Chemical-shift values from Table 2.
b The assignments of H-6 and H-6% are shown in Fig. 1.
c Typical downfield shift of the signal from the proton of the a-carbon atom on O-acylation [6].
d Upfield shift upon O-acylation of C-4, attributable to a diamagnetic anisotropic shielding effect exerted by the introduced
carbonyl group on H-6 in rotamers a1 and a3, and on H-6% in rotamer a3 (Fig. 1).
Table 5
13C NMR chemical-shift correlations for compounds 8–11
Dl (ppm)a for indicated compounds
Atom
C-1
C-2
C-3
C-4
C-5
C-6
10–8
11–8
10–9
+0.35
+0.30
+0.32
+0.30
+0.22
−2.71b
−3.57b
−3.32b
−0.87
+0.23
−0.61
−2.64b
−2.37b
−2.51b
+0.15
−0.29
−0.63
−0.24
a Chemical-shift values from Table 3.
b Typical upfield shift of the signal from the b-carbon atom on O-acylation [7].
1,2,3,4,6-penta-O-benzoyl- -glucopyranoses
D
from O-3 to O-2 to give the 2,4,6-tribenzoate,
followed by a migration from O-4 to O-3 to
give the 2,3,6-tribenzoate. These migrations
must accompany or follow the formation of
containing 14C-labeled benzoyloxy groups at-
tached to different carbon atoms (2–6). In
each case, compound 8, N-benzoylpiperidine,
and benzoic acid were isolated from the reac-
tion mixture. From the activity data of sub-
strates and products, the moles of labeled
benzoyl groups per mol in the products were
calculated (Table 6). The contributions of
each benzoyl group of 1,2,3,4,6-penta-O-benz-
the glucosylamine linkage, since in -glucopy-
D
ranose derivatives acyl migrations generally
proceed away from C-1 and towards C-6. It
has been reported [13] that in the monoac-
etates of methyl 6-O-trityl-a- -glucopyran-
D
oside, acetyl migration under mild alkaline
conditions takes place in the direction O-2
“O-3“O-4.
oyl- -glucopyranose to the formation of 8,
D
N-benzoylpiperidine, and piperidinium ben-
zoate are indicated in Table 7. These results
indicate that benzoyloxy-C-1 of the substrate
is removed mostly as N-benzoylpiperidine,
piperidinium benzoate is formed mainly at the
expense of benzoyloxy-C-2, and the benz-
oyloxy groups originally attached to C-3, C-4,
and C-6 are entirely recovered in the major
product 8. This is a clear proof that the first
compound formed in the reaction should be
The mechanism of the reaction of 1 with
piperidine was studied by employing five
N-(3,4,6-tri-O-benzoyl-b- -glucopyranosyl)pi-
D

A.E. Salinas / Carbohydrate Research 20 (1999) 34–46
39
Table 6
Moles of labeled benzoyl groups per mola in the products isolated from the reaction of labeled 1,2,3,4,6-penta-O-benzoyl-
D
-glu-
copyranoses with piperidine
Substrate
Carbon atoms with labeled benzoyloxy groups
Products
8
N-Benzoylpiperidine
Benzoic acid
2
3
4
5
6
C-1
C-4
C-6
C-1, C-2, C-3
C-1, C-3, C-4
0.02b
1.00
0.99
1.00
2.00
0.86
0.01b
0.06
0.93
0.88
0.04
0.10
0.01b
0.89
0.25
a Calculated as: activity of the product/activity per labeled benzoyl group of the substrate.
b Values within the error of the method employed.
Table 7
Contributions of benzoyl groups of 1,2,3,4,6-penta-O-benzoyl-D-glucopyranose to the formation of 8, N-benzoylpiperidine, and
piperidinium benzoatea
Location of the benzoyloxy group in the substrate
8
N-benzoylpiperidine
Piperidinium benzoate
C-1
C-2
C-3
C-4
C-6
0.02b
0.00c
0.98d
1.00
0.86
0.04
0.06c
0.01b,d
0.01b
0.06
0.74c
0.11d
0.10
0.99
0.01b
a Expressed in moles of benzoyl group per mol of product.
b Values within the error of the method employed.
c Values calculated by subtracting the individual contributions of benzoyloxy-C-1 and benzoyloxy-C-3 from the total
contribution of the benzoyloxy groups attached to C-1, C-2, and C-3.
d Values calculated by subtracting the individual contribution of benzoyloxy-C-1 and benzoyloxy-C-4 from the total contribu-
tion of the benzoyloxy groups attached to C-1, C-3, and C-4.
peridine, which could not be isolated because
it undergoes two consecutive benzoyl migra-
tions: a migration from O-3 to O-2 to give 9,
followed by a migration from O-4 to O-3 to
give 8. These migrations of benzoyl groups in
transfer increases. In
D
-glucopyranose deriva-
tives, the anomeric carbon bears two electron-
withdrawing oxygen atoms; consequently, the
acidity of hydroxyl groups increases in a di-
rection towards C-1, favoring the acyl migra-
tions away from the anomeric center. In
a direction towards C-1 in N-b- -glucopyran-
D
osylpiperidine derivatives are apparent excep-
tions to the generalization [14] that in par-
tially acylated monosaccharides, acyl mi-
grations take place away from the anomeric
center. It is known that the intramolecular
O“O acyl transfer is a reversible base-cata-
lyzed reaction which proceeds through a
cyclic anionic addition intermediate [13]. The
position of the equilibrium is strongly depen-
dent on the ‘acidity’ of the hydroxyl groups
involved in the acyl transfer, as in intermolec-
ular acyl-transfer processes. It has been re-
ported [15], that as the acidity of the acceptor
hydroxyl group decreases, the rate of acyl
N- -glucopyranosylpiperidine derivatives, the
D
observed acyl migrations in a direction to-
wards C-1 might be a consequence of the
replacement of an oxygen atom at C-1 by a
less electronegative nitrogen atom, thus reduc-
ing the electron-withdrawing effect of the
anomeric center.
In order to rationalize the different results
obtained [2] in the analogous reaction of
penta-O-acetyl-b- -glucopyranose (7) with
D
piperidine, this reaction was repeated in the
same conditions described by Hodge and Rist.
From the reaction mixture, N-(3,4,6-tri-O-
acetyl - b -
D
- glucopyranosyl)piperidine (12)

40
A.E. Salinas / Carbohydrate Research 20 (1999) 34–46
slowly crystallized; chromatography of the
might be explained considering that acetoxy
groups of 13 undergo aminolysis by piperidine
at a greater rate than benzoyloxy groups of 8.
This was corroborated by studying the stabil-
ity of these compounds in piperidine–ether
after a reaction period of 6 days. Starting
from 12, 13, or 14, N-acetylpiperidine was an
important component of the reaction mix-
tures. On the contrary, starting from 8, 9, or
10, N-benzoylpiperidine could not be detected
in the reaction media.
mother liquor from the crystallization of 12
affordedN-(2,3,6-tri-O-acetyl-b- -glucopyran-
D
osyl)piperidine (13) and N-(2,3,4,6-tetra-O-
acetyl - b - - glucopyranosyl)piperidine (14).
D
(Table 1). In the reaction of 7 with piperidine,
the product primarily formed by O-deacetyl-
ation at C-1 and C-2 of the substrate could be
isolated because it is scarcely soluble in the
reaction medium and crystallizes sponta-
neously. The high yield of 12 is not necessarily
a consequence of the greater stability of 12
compared to 13, since external factors such as
solubility can influence the equilibrium [16].
When the reaction of 7 with piperidine was
performed under homogeneous conditions,
only compounds 13 and 14 could be isolated
in low yield by chromatography. Compound
12 was not detected in the reaction mixture
because it undergoes two consecutive acetyl
migrations in a direction towards C-1 to give
13. The low yield of 13 (4.1%) contrasts with
the yield obtained for 8 in the similar reaction
of 1 with piperidine (44.1%). The difference
The
osyl)piperidine could presumably have been
formed from a penta-O-acyl- -glucopyranose
N-(2,3,6-tri-O-acyl-b-
D
-glucopyran-
D
(19) by the reaction pathway depicted in
Scheme 1. In a first step, the acyloxy-C-1 of
the substrate, which is aminolyzed at a greater
rate than the remaining acyloxy groups, is
removed as N-acylpiperidine. Calculations
[17] showed that in the resulting 2,3,4,6-tetra-
O-acyl- -glucopyranose (20) the HO–C-1 is
D
highly ionized in an aprotic reaction medium.
This was corroborated in the present work by
the isolation, at the beginning of the reaction,
Scheme 1.

A.E. Salinas / Carbohydrate Research 20 (1999) 34–46
41
of a 1:1 salt-like adduct of 2,3,4,6-tetra-O-
benzoyl- -glucopyranose and piperidine. The
D
ionization of the hemiacetal facilitates the
opening of the pyranoid ring that generates
the carbonyl group (21). Nucleophilic addition
of piperidine leads to the carbinolamine 22,
highly ionized in aprotic media [17]. In-
tramolecular attack of the oxyanion from C-1
on the carbonyl group of acyloxy-C-2 results
in the formation of intermediate 23, which
subsequently decomposes expelling a car-
boxylate anion to give the iminium cation 24.
Nucleophilic attack of O-5 leads to a N-(3,4,6-
Fig. 1. The staggered rotamers of the C-5–C-6 fragment in
N-(b- -glucopyranosyl)piperidine derivatives. Rotamer a2
D
(H-5 trans-coplanar to H-6%) can be excluded as a significant
contributor to the conformational population because of the
low values of J5,6% (Table 2); this exclusion would be ex-
pected as this rotamer has a destabilizing 1,3-parallel inter-
action between O-4 and O-6. The intermediate values of J5,6
(Table 2) accord with an equilibrium in which rotamers a1
(H-5 gauche to H-6) and a3 (H-5 trans-coplanar to H-6)
both contribute significantly.
tri-O-acyl-b- -glucopyranosyl)piperidine (25),
D
which could be isolated only in the reaction of
7 with piperidine under crystallizing condi-
tions. A first O-3“O-2 acyl migration pro-
duces the 2,4,6-tri-O-acyl derivative 26, that
was isolated as a minor product in the reac-
tion of 1 with piperidine. A subsequent O-4“
O-3 acyl migration produces the 2,3,6-
tri-O-acyl derivative 27, that was the major
product isolated in the reaction of 1 with
piperidine, and in the reaction of 7 with pipe-
ridine under homogeneous conditions.
Bruker AC-200 spectrometer operating at 200
MHz for 1H and 50.2 MHz for 13C. Me4Si was
employed as the internal reference-standard.
Signal multiplicities are indicated by: bs,
broad singlet; d, doublet; dd, double doublet;
m, multiplet; s, singlet; t, triplet. The two
magnetic nonequivalent geminal protons at
C-6 are denoted H-6 and H-6% as shown in
Fig. 1. The geminal coupling constant J6,6% was
assumed to be negative, in analogy to the data
on geminal coupling constants for other satu-
rated carbohydrates [18]. Hydroxyl protons
were exchanged for deuterium by adding D2O.
The two-dimensional 1H–1H and 13C–1H
chemical-shift correlated spectra were ob-
tained with the standard COSY and HET-
COR pulse sequences. Benzoyl [carbonyl-14C]-
chloride was prepared from benzoic [carboxyl-
14C]acid and unlabeled benzoic acid, accord-
ing to Schmid and Banholzer [19]. The activity
of the product was determined by hydrolysis
to benzoic acid. Labeled 1,2,3,4,6-penta-O-
3. Experimental
General methods.—Melting points were de-
termined with a Fisher–Johns apparatus and
are uncorrected. Optical rotations were mea-
sured with a Perkin–Elmer 141 polarimeter.
Solvents were distilled prior to use. Ligroin
had bp 100–120 °C. Evaporations were con-
ducted below 40 °C under diminished pres-
sure. Samples for analysis were dried under
vacuum over P2O5. Column chromatography
was performed on Alumina Woelm neutral,
activity grade I. TLC on alumina was con-
ducted on glass plates (10×20 cm) coated
with Aluminium oxide G, type E (E. Merck;
0.25-mm thickness). Detection was effected
with iodine vapor. TLC on silica gel was done
on aluminium sheets precoated with Silica Gel
60 F (E. Merck; 0.2-mm thickness). Detection
was effected by charring with 10% H2SO4
(v/v) in EtOH. The following mixtures of hex-
ane–EtOAc (v/v) were used as developing sol-
vents: A, 4:1; B, 7:3; C, 3:2. NMR spectra
were recorded for solutions in CDCl3 on a
benzoyl- -glucopyranoses were recrystallized
D
to constant specific activity. Activities were
measured with a Rackbeta Wallack 1214 liq-
uid scintillation counter. The scintillation so-
lution contained 400 mg of 2,5-di-
phenyloxazole (PPO) and 10 mg of 1,4-bis-2-(4-
methyl-5-phenyloxazolyl)-benzene (di-methyl
POPOP) per 100 mL of toluene. Activities are
expressed as disintegrations per min per mmol
(dpm/mmol).
Preparation of
-glucopyranose (1).—Compound 1 was pre-
1,2,3,4,6-penta-O-benzoyl-i-
D

42
A.E. Salinas / Carbohydrate Research 20 (1999) 34–46
which was dissolved in Et2O (15 mL) and
pared from -glucose by following the method
D
precipitated by adding ligroin (15 mL); crys-
tals were obtained (209 mg, 1.5%); Rf 0.34
(alumina, solvent A). A further recrystalliza-
tion from the same solvent mixture gave 9: mp
180–181 °C (d); [h]D +33.5° (c 0.4, CHCl3);
described by Ness et al. [20] for the b anomer.
The crude product was successively recrystal-
lized from glacial HOAc, 5:1 acetone–water
and 3:1 MeOH–acetone; a pure product was
obtained having mp 158–160 °C, [h]D +23.9°
(c 1, CHCl3), in agreement with the values
reported in the literature [20,21].
1
13
for H and C NMR data see Tables 2 and 3.
Anal Calcd for C32H33NO8: C, 68.68; H, 5.94;
N, 2.50. Found: C, 68.90; H, 5.84; N, 2.65.
Reaction of 1 with piperidine.—Compound
1 (17.5 g, 25 mmol) was suspended in dry
Et2O (250 mL) and piperidine (15 mL, 150
mmol) was added. The mixture was stirred for
6 days at rt, solution being attained after
about 5 days. The solution was evaporated to
a thick dark-yellow syrup (27.1 g), that was
dissolved in Et2O (250 mL) and extracted with
water (4×50 mL). The aq extract containing
piperidinium benzoate was acidified with
concd HCl and cooled to 0 °C; 2.75 g of
benzoic acid were obtained, mp 121–122 °C,
identical with an authentic sample.
The ether layer was evaporated to a syrup
(19.35 g). Examination by TLC on alumina
(solvent A) showed four spots, Rf 0.70, 0.48,
0.34, and 0.24. The syrup was chro-
matographed on a dry-column of alumina
(1200 g); elutions were performed by using
hexane with increasing concentrations of
EtOAc. Fractions (400 mL each) were col-
lected, and monitored by TLC. Elution with
9:1 hexane–EtOAc afforded the products hav-
ing Rf 0.70 (fractions 17–19) and Rf 0.48
(fractions 20–25), while a 4:1 mixture of the
same solvents eluted the components having
Rf 0.34 (fractions 39–41) and Rf 0.24 (frac-
tions 42–60).
2,4,6-Tri-O-benzoyl-h- -glucopyranose
D
(16).—To a solution of 9 (60 mg, 0.107 mmol)
in 3:1 acetone–water (4.8 mL) was added
Amberlite IR-120 (H+) resin (240 mg). The
suspension was stirred at rt for 24 h, filtered
and the filtrate evaporated to dryness. The
amorphous residue crystallized (51 mg, 96.6%)
from toluene; examination by TLC on silica
gel (solvent C) showed two spots having Rf
0.48 and 0.42. The relative intensities of the
C-1 resonance signals in the 13C NMR spec-
trum indicated that this product was a 7:2
mixture of a and b anomers. Two recrystal-
lizations from benzene gave 16: mp 122–
124 °C, lit 124–126 °C [8]; [h]D +78.9° (c 0.3,
EtOH), lit +81.6° [8]; Rf 0.48 (silica gel,
1
solvent C); H NMR data: l 5.63 (d, J1,2 3.5
Hz, H-1), 5.13 (dd, J2,3 9.9 Hz, H-2), 4.51 (t,
J3,4 9.5 Hz, H-3), 5.42 (t, J4,5 9.5 Hz, H-4),
4.61 (m, H-5), 4.42 (dd, J5,6 4.0, J6,6% −11.5
Hz, H-6), 4.65 (dd, J5,6% 2.6 Hz, H-6%), 7.25–
8.11 (15 H, Ph), 2.60 and 3.05 (2 bs, 2 OH,
disappeared on deuteration); 13C NMR data:
l 90.53 (C-1), 74.23 (C-2), 69.97 (C-3), 72.21
(C-4), 67.57 (C-5), 63.09 (C-6), 128.34–133.62
(Ph), 166.21 (×2), 166.32 (3 COPh).
N-(2,3,6-Tri-O-benzoyl-i- -glucopyranosyl)-
D
piperidine (8).—Evaporation of fractions 42–
60 afforded a crystalline residue (8.36 g) which
was dissolved in Et2O (140 mL) and precipi-
tated by adding ligroin (140 mL); crystals
were obtained (6.16 g, 44.1%); Rf 0.24 (alu-
mina, solvent A). A further recrystallization
from the same solvent mixture gave 8: mp
151–152 °C (d); [h]D +67.3° (c 0.5, CHCl3);
Evaporation of fractions 17–19 gave a
syrupy residue (83 mg, 0.5%) that crystallized
from 1:1 Et2O–ligroin yielding 10: mp 146–
147 °C (d); [h]D+36.3° (c 0.4, CHCl3); Rf 0.70
(alumina, solvent A), identical with an authen-
tic sample prepared on benzoylation of 8.
Fractions 20–25 were evaporated to a syrup
(4.82 g) that crystallized on standing in a
refrigerator: mp 45–50 °C; Rf 0.48 (alumina,
solvent A). It was identified as N-benzoylpip-
eridine by comparison with an authentic sam-
ple; lit mp 48 °C [22].
1
13
for H and C NMR data see Tables 2 and 3.
Anal Calcd for C32H33NO8: C, 68.68; H, 5.94;
N, 2.50. Found: C, 68.59; H, 5.76; N, 2.72.
2,3,6-Tri-O-benzoyl-h- -glucopyranose (15).
D
—To a solution of 8 (600 mg, 1.07 mmol) in
3:1 acetone–water (48 mL) was added Amber-
lite IR-120 (H+) resin (2.4 g). The suspension
was stirred at rt for 24 h, filtered and the
N-(2,4,6-Tri-O-benzoyl-i- -glucopyranosyl)-
D
piperidine (9).—Evaporation of fractions 39–
41 gave a partially crystalline residue (285 mg)

A.E. Salinas / Carbohydrate Research 20 (1999) 34–46
43
Chromatographic purification on a dry-
column of alumina with 17:3 hexane–EtOAc
as the eluent gave 10 (2.99 g, 72%), which
crystallized from 1:1 Et2O–ligroin: mp 148–
filtrate evaporated to dryness. The amorphous
residue crystallized (501 mg, 95%) from
toluene; examination by TLC on silica gel
(solvent C) showed two spots having Rf 0.44
and 0.38. The relative intensities of the C-1
resonance signals in the 13C NMR spectrum of
the product revealed that it was a 7:3 mixture
of a and b anomers. Four recrystallizations
from 1:1 Et2O–ligroin gave 15, mp 165–
166 °C; [h]D+141.3° (c 0.5, CHCl3); Rf 0.44
1
149 °C (d); [h]D+36.7° (c 0.5, CHCl3); for H
13
and C NMR data see Tables 2 and 3. Anal.
Calcd for C39H37NO9: C, 71.00; H, 5.04; N,
2.12. Found: C, 70.97; H, 5.33; N, 2.01.
Preparation of 2,3,4,6-tetra-O-benzoyl-h- -
D
glucopyranose (17).—Compound 10 (2.4 g,
3.62 mmol) was suspended in 2:1 acetone–wa-
ter (80 mL) and Amberlite IR-120 (H+) resin
(10 g) was added. The mixture was stirred at
50 °C for 1 h and then at rt for 24 h. The
suspension was filtered and the filtrate evapo-
rated to dryness. The amorphous residue crys-
tallized (2.1 g, 97%) from 1:1 Et2O–ligroin;
examination by TLC on silica gel (solvent B)
showed two spots having Rf 0.40 and 0.33.
1
(silica gel, solvent C); H NMR data: l 5.66
(d, J1,2 3.5 Hz, H-1), 5.27 (dd, J2,3 10.1 Hz,
H-2), 5.89 (t, J3,4 9.7 Hz, H-3), 3.91 (m, J4,5
9.9, J4,OH 4.3 Hz, H-4; triplet on deuteration),
4.39 (m, H-5), 4.77 (dd, J5,6 3.7, J6,6% −12.1
Hz, H-6), 4.63 (dd, J5,6% 1.9 Hz, H-6%), 7.25–
8.09 (15 H, Ph), 3.53 and 3.80 (2 bs, 2 OH,
disappeared on deuteration); 13C NMR data:
l 90.57 (C-1), 71.76 (C-2), 73.46 (C-3), 69.63
(C-4), 70.23 (C-5), 63.43 (C-6), 128.40–133.36
(Ph), 165.96, 167.02, 167.35 (3 COPh). Anal.
Calcd for C27H24O9: C, 65.85; H, 4.91. Found:
C, 66.08; H, 5.15.
1
Integration of the H NMR spectrum in the
region of the H-3 resonance signals revealed
that the product was a 4:1 mixture of a and b
anomers. Recrystallization from ligroin gave
17 (1.38 g, 64%): mp 118–120 °C, lit 117–
120 °C [9]; [h]D +74.9° (c 0.5, CHCl3), lit +
N-(4-O-Acetyl-2,3,6-tri-O-benzoyl-i-
copyranosyl)piperidine (11).—Compound
D
-glu-
8
1
(300 mg, 0.54 mmol) was dissolved in pyridine
(0.6 mL) and treated with Ac2O (0.3 mL, 3.18
mmol) at 0 °C. The solution was kept for 3
days in a refrigerator and then evaporated in
vacuo over H2SO4 and KOH. The resulting
crystalline residue was recrystallized from
MeOH to give 11 (194 mg, 60%): mp 181–
72.4° [9]; Rf 0.40 (silica gel, solvent B); H
NMR data: l 5.72 (d, J1,2 3.5 Hz, H-1), 5.30
(dd, J2,3 10.2 Hz, H-2), 6.28 (t, J3,4 9.9 Hz,
H-3), 5.72 (t, J4,5 9.8 Hz, H-4), 4.69 (m, H-5),
4.48 (dd, J5,6 4.5, J6,6% −12.1 Hz, H-6), 4.63
(dd, J5,6% 3.1 Hz, H-6%), 7.25–8.08 (20 H, Ph),
3.90 (bs, OH, disappeared on deuteration); 13C
NMR data: l 90.53 (C-1), 72.44 (C-2), 70.44
(C-3), 69.69 (C-4), 67.76 (C-5), 63.03 (C-6),
128.38-133.38 (Ph), 165.25, 165.89 (×2),
166.37 (4 COPh).
1
182 °C (d); [h]D +95.1° (c 0.5, CHCl3); for H
13
and C NMR data see Tables 2 and 3. Anal.
Calcd for C34H35NO9: C, 67.89; H, 5.82; N,
2.33. Found: C, 67.69; H, 6.00; N, 2.50.
N-(2,3,4,6-Tetra-O-benzoyl-i-
D
-glucopyran-
Reaction of 17 with piperidine. Adduct of
osyl)piperidine (10).—A solution of 8 (3.5 g,
6.26 mmol) in pyridine (14 mL) was cooled to
0 °C and benzoyl chloride (2.1 mL, 18.09
mmol) was slowly added. The mixture was
kept for 3 days in a refrigerator and then
poured into ice-cold 5% aq NaHCO3 (70 mL).
After being kept for 1 h with occasional shak-
ing until evolution of gas ceased, the mixture
was extracted with CHCl3 (3×70 mL). The
organic extract was washed with water (2×70
mL), dried (Na2SO4), and evaporated to a
syrup that failed to crystallize. Examination
by TLC (alumina, solvent A), revealed the
presence of a major component, Rf 0.70.
2,3,4,6-tetra-O-benzoyl- -glucopyranose and
D
piperidine.—Compound 17 (596 mg, 1 mmol)
was suspended in dry Et2O (10 mL) and pip-
eridine (0.6 mL, 6 mmol) was added. The
resulting solution was kept at rt; after a few
minutes crystallization began. The reaction
mixture was cooled to 0 °C and the crystals
deposited were filtered off (595 mg, 87.4%):
mp 101–103 °C (d); [h]D +56.7° (c 0.5,
1
CHCl3). The H NMR spectrum revealed that
the product was a 1:1 adduct of 2,3,4,6-tetra-
O-benzoyl- -glucopyranose and piperidine;
D
integration of the H-3 signals showed that the
tetrabenzoate was present in the adduct as a

44
A.E. Salinas / Carbohydrate Research 20 (1999) 34–46
mmol) was added. The reaction mixture was
stirred for a few minutes until dissolution of
the crystalline precipitate initially formed. The
solution was stored for 3 days at rt and then
evaporated to a dark-yellow syrup (224 mg).
Examination by TLC on alumina (solvent A)
revealed the presence of compounds 8 (Rf
0.24) and 9 (Rf 0.34). Chromatographic sepa-
ration of the syrup on a dry-column of alu-
mina using 4:1 hexane–EtOAc as the eluent,
followed by crystallization from 1:1 Et2O–
ligroin gave 8 (118 mg, 52.7%), mp 150–
152 °C (d), and 9 (4 mg, 1.8%), mp
176–178 °C (d). They were identified by com-
parison with authentic samples.
4:1 mixture of a and b anomers. The N–H
signal of piperidine was shifted in the adduct
from l 1.40 to 3.90 and appeared as a broad
singlet superimposed with the HO–C-1 signal
of the tetrabenzoate. Anal. Calcd for
C39H39NO10: C, 68.72; H, 5.73; N, 2.06.
Found: C, 68.57; H, 6.01; N, 1.80.
The reaction was repeated under the same
conditions with a further amount (596 mg) of
17. The crystalline precipitate formed was not
separated, and the reaction mixture was kept
with stirring for 6 days at rt, solution being
attained after about 4 days. Evaporation of
the solution afforded a thick dark yellow
syrup (823 mg); it was dissolved in Et2O (10
mL) and extracted with water (4×2 mL). On
acidifying the aq extract with concd HCl and
cooling to 0 °C, 109 mg of benzoic acid were
obtained: mp 122–123 °C.
Preparation of labeled 1,2,3,4,6-penta-O-
benzoyl- -glucopyranoses
D
2,3,4,6-tetra-O-benzoyl-1-O-[carbonyl-14C]-
benzoyl-h- -glucopyranose (2). A solution of
D
17 (2 g, 3.36 mmol) in pyridine (8 mL) was
cooled to −20 °C and Ph[14C]COCl (1.2 mL,
10.34 mmol; activity 1.71×105 dpm/mmol)
was slowly added. The mixture was kept for 3
days in a refrigerator and then poured into
ice-cold 5% aq NaHCO3. After standing
overnight in the refrigerator, the solid de-
posited was pulverized, filtered off, washed
with water, soaked in MeOH and dried. After
three recrystallizations from 3:1 MeOH–ace-
tone a pure product was obtained having mp
191–192 °C; [h]D +137.4° (c 0.5, CHCl3), in
agreement with the values reported in the lit
for the a anomer [20]; activity 1.67×105 dpm/
mmol.
The organic layer was evaporated to a
syrup (527 mg). Examination by TLC on alu-
mina (solvent A) showed the presence of com-
pounds 8 (Rf 0.24), 9 (Rf 0.34), 10 (Rf 0.70),
and traces of N-benzoylpiperidine (Rf 0.48).
Chromatographic separation of the syrup was
performed as described for the analogous re-
action of 1 with piperidine. Crystallization of
the products isolated from 1:1 Et2O–ligroin
gave 8 (300 mg, 53.7%), mp 152–153 °C (d), 9
(13 mg, 2.3%), mp 178–180 °C (d), and 10 (8
mg, 1.2%), mp 147–148 °C (d). They were
identified by comparison with authentic
samples.
1,2,3,6-Tetra-O-benzoyl-4-O-[carbonyl-14C]-
Treatment of 8, 9, and 10 with piperidine–
ether.—Samples (10 mg) of each compound
were separately dissolved in 1:9 (v/v) pipe-
ridine–Et2O (0.5 mL). The solutions were
stored at rt for 6 days and then evaporated in
vacuo. The resulting residues were examined
by TLC on alumina (solvent A). Starting from
8 or 9 indistinctly, the reaction mixture
showed two spots: a main spot having Rf 0.24
(compound 8) and a minor one having Rf 0.34
(compound 9). Starting from 10, the reaction
mixture showed only one spot having Rf 0.70
(compound 10).
benzoyl-i-
O-benzoyl-6-O-[carbonyl-14C]benzoyl-i-
glucopyranose (4), and 4,6-di-O-benzoyl-1,2,3-
tri-O-[carbonyl-14C]benzoyl-i-
-glucopyranose
D
-glucopyranose (3), 1,2,3,4-tetra-
D
-
D
(5). Compounds 3, 4, and 5 were prepared as
described by Gros et al. [23]. Compound 3
had mp 165–167 °C; [h]D +23.3° (c 0.5,
CHCl3); activity 4.15×106 dpm/mmol; calcd
activity after isotopic dilution with 1, 6.63×
105 dpm/mmol. Compound 4 had mp 161–
163 °C; [h]D+21.8° (c 0.5, CHCl3); activity
4.30×106 dpm/mmol; calcd activity after iso-
topic dilution with 1, 8.59×105 dpm/mmol.
Compound 5 had mp 166–168 °C; [h]D +
20.2° (c 0.5, CHCl3); activity 3.99×106 dpm/
mmol; activity per labeled benzoyl group
1.33×106 dpm/mmol.
Reaction of 3,4,6-tri-O-benzoyl-h- -glu-
D
copyranose (18) with piperidine.—Compound
18 (197 mg, 0.2 mmol), mp 165–167 °C,
[h]D+55° (c 0.5, EtOH) [8] was dissolved in
dry Et2O (4 mL) and piperidine (0.24 mL, 2.4

A.E. Salinas / Carbohydrate Research 20 (1999) 34–46
45
2,6-Di-O-benzoyl-1,3,4-tri-O-[carbonyl-14C]-
benzoyl-h- -glucopyranose (6). Compound 6
was prepared from 2,6-di-O-benzoyl-a- -glu-
tallizing conditions. N-(3,4,6-tri-O-acetyl-i- -
D
D
glucopyranosyl)piperidine (12).—Compound 7
(10 g, 25 mmol) was suspended in dry Et2O
(25 mL) and piperidine (10 mL, 100 mmol)
was added. The mixture was stirred for 20
min at rt until complete dissolution of 7.
Hexane (15 mL) was added, and the homoge-
neous mixture was kept in a refrigerator
overnight. The crystalline precipitate that
slowly formed was filtered off, washed by
stirring it with absolute EtOH (40 mL) and
dried to give 12 (3.10 g, 33.2%): mp 136–
137 °C (d) (browning from 130 °C),
lit 125 °C (d) [2]; [h]D +34.6° (c 0.5, CHCl3),
lit +31.6° [2]; Rf 0.23 (alumina, solvent B);
D
copyranose [24] (2 g, 5.15 mmol) by benzoyl-
ation with Ph[14C]COCl (4.5 mL, 38.76
mmol; activity 1.10×106 dpm/mmol) and
pyridine (10 mL), in the same conditions em-
ployed for the preparation of 2. The product
obtained had mp 190–191 °C; [h]D+135.2° (c
0.5, CH-Cl3); activity 3.30×106 dpm/mmol;
activity per labeled benzoyl group 1.10×106
dpm/mmol.
Reaction of 2, 3, 4, 5, and 6 with piper-
idine.—The labeled compound (350 mg, 0.5
mmol) was suspended in dry Et2O (5 mL)
and piperidine (0.5 mL, 3 mmol) was added.
The mixture was stirred for 6 days at rt; the
isolation of 8, N-benzoylpiperidine, and benz-
oic acid was carried out as described for the
reaction of 1 with piperidine. The yields of
the labeled products were in all cases similar
to those reported for the unlabeled ones.
Compound 8 and benzoic acid were recrystal-
lized to constant specific activity. N-benz-
oylpiperidine failed to crystallize; further
purification was accomplished by dry-column
chromatography on alumina with 9:1 hex-
ane–EtOAc as the eluent. The resulting chro-
matographically homogeneous syrup, Rf 0.48
(alumina, solvent A), was dried at rt/0.13 Pa
before measuring the activity.
1
for H NMR data see Table 2.
The filtrate and washings were combined
and evaporated to a dark-yellow liquid
residue (12.98 g). Examination by TLC on
alumina (solvent B) showed four spots, Rf
0.83, 0.52, 0.32, and 0.07. The residue was
dissolved in Et2O (100 mL) and extracted
with water (5×20 mL); piperidinium acetate
(Rf 0.07) and most of the N-acetylpiperidine
(Rf 0.52) were thus removed. The ether layer
was evaporated to a syrup (5.02 g); TLC of
the residue showed the presence of a major
component (Rf 0.32), a minor one (Rf 0.83),
and traces of N-acetylpiperidine (Rf 0.52).
The syrup was chromatographed on a dry-
column of alumina (300 g); elutions were per-
formed by using hexane with increasing
concentrations of EtOAc. Fractions (100 mL
each) were collected, and monitored by TLC.
Elution with 3:1 hexane–EtOAc afforded the
product having Rf 0.83 (fractions 12–14),
and a 13:7 mixture of the same solvents
eluted the component having Rf 0.32 (frac-
tions 29–36).
Compound 2 gave 8, activity 0.03×105
dpm/mmol; N-benzoylpiperidine, activity
1.43×105 dpm/mmol; benzoic acid, activity
0.07×105 dpm/mmol. Compound 3 gave 8,
activity 6.62×105 dpm/mmol; N-benz-
oylpiperidine, activity 0.09×105 dpm/mmol;
benzoic acid, activity 0.69×105 dpm/mmol.
Compound 4 gave 8, activity 8.54×105 dpm/
mmol; N-benzoylpiperidine, activity 0.51×
105 dpm/mmol; benzoic acid, activity 0.11×
105 dpm/mmol. Compound 5 gave 8, activity
1.33×106 dpm/mmol; N-benzoylpiperidine,
activity 1.23×106 dpm/mmol; benzoic acid,
activity 1.18×106 dpm/mmol. Compound 6
gave 8, activity 2.20×106 dpm/mmol; N-
benzoylpiperidine, activity 0.97×106 dpm/
mmol; benzoic acid, activity 0.28×106 dpm/
mmol.
N-(2,3,4,6-Tetra-O-acetyl-i- -glucopyran-
D
osyl)piperidine (14).—Evaporation of frac-
tions 12–14 gave a solid residue (52 mg,
0.5%), which crystallized from 1:1 Et2O–
ligroin yielding 14: mp 122–123 °C, lit 123 °C
[25]; [h]D −3.5° (c 0.5, CHCl3), lit −3.5°
1
[25]; Rf 0.83 (alumina, solvent B); for H
NMR data see Table 2.
N-(2,3,6-Tri-O-acetyl-i- -glucopyranosyl)-
D
piperidine (13).—Evaporation of fractions
29–36 afforded a colorless amorphous solid
Reaction of 1,2,3,4,6-penta-O-acetyl-i-
D
-
glucopyranose (7) with piperidine under crys-

46
A.E. Salinas / Carbohydrate Research 20 (1999) 34–46
Acknowledgements
(168 mg, 1.8%), Rf 0.32 (alumina, solvent B);
by dissolving it in Et2O (2.5 mL) and adding
ligroin (2.5 mL) crystals of 13 were ob-
tained: mp 127–128 °C (d) (browning from
The author is indebted to UMYMFOR
(CONICET-FCEN, Buenos Aires) for the mi-
croanalyses and spectra. Thanks are expressed
to Dr E.G. Gros for providing the labeled
compounds 3, 4, and 5, the 2,6-di-O-benzoyl-
1
125 °C); [a]D −24.8° (c 0.5, CHCl3); for H
NMR data see Table 2. Anal. Calcd for
C17H27NO8: C, 54.69; H, 7.24; N, 3.75.
Found: C, 54.72; H, 7.38; N, 3.74.
a- -glucopyranose used in the preparation of
D
compound 6, and for reviewing the original
The rest of the chromatographed material
was retained in the column and could not be
eluted even with EtOAc, presumably due to
alteration when brought into contact with
the adsorbent.
manuscript.
References
Reaction of 7 with piperidine under homo-
geneous conditions.—Compound 7 (4 g, 10
mmol) was suspended in dry Et2O (100 mL)
and piperidine (4 mL, 40 mmol) was added.
The mixture was stirred until complete disso-
lution of 7 and kept at rt for 5 days. It was
then evaporated to a dark-yellow liquid
residue (6.4 g), which on examination by
TLC (alumina, solvent B) revealed the pres-
ence of compounds 13 (Rf 0.32), 14 (Rf
0.83), N-acetylpiperidine (Rf 0.52), and pip-
eridinium acetate (Rf 0.07). The residue was
processed and chromatographed as described
for the previous reaction of 7 with pip-
eridine. Crystallization of the products iso-
lated from 1:1 Et2O–ligroin gave 13 (152
mg, 4.1%), mp 126–127 °C (d), and 14 (12
mg, 0.3%), mp 121–122 °C, identical with
authentic samples.
Treatment of 12, 13, and 14 with piper-
idine–ether.—Samples (10 mg) of each com-
pound were separately treated with 1:9 (v/v)
piperidine–Et2O (0.5 mL). As compound 12
remained insoluble, the reaction mixture was
stirred for 2 days until complete dissolution
of 12. The solutions were stored at rt for 6
days and then evaporated in vacuo. The re-
sulting residues were examined by TLC on
alumina (solvent B). Starting from 12 or 13
indistinctly, the reaction mixture showed
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