Structure and reactivity of glycosides: IV. Koenigs-Knorr synthesis of aryl β-D-glucopyranosides using phase-transfer catalysts

Article abstract of DOI:10.1023/A:1013971214679

A series of acetylated aryl β-D-glucopyranosides were prepared in 12-63% yields from tetra-O-acetyl-α-D-glycopyranosyl bromide and phenols containing acyl, formyl, and hydroxy substituents, and also from sterically hindered phenols in the two-phase system chloroform-aqueous alkali in the presence of triethylbenzylammonium chloride. Hydroxyethylated sucrose and dibenzo-18-crown-6 do not behave as phase-transfer catalysts in glycosylation of phenols. 2001 MAIK "Nauka/Interperiodica".

Full text of DOI:10.1023/A:1013971214679

Russian Journal of General Chemistry, Vol. 71, No. 11, 2001, pp. 1811 1814. Translated from Zhurnal Obshchei Khimii, Vol. 71, No. 11, 2001,
pp. 1915 1919.
Original Russian Text Copyright
2001 by Pavlov, Sokolov, Zakharov.
Structure and Reactivity of Glycosides:
IV.1 Koenigs Knorr Synthesis of Aryl -D-Glucopyranosides
Using Phase-Transfer Catalysts
A. E. Pavlov, V. M. Sokolov, and V. I. Zakharov
St. Petersburg State Institute of Technology, St. Petersburg, Russia
Research and Production Association of Pulp-and-Paper Industry, St. Petersburg, Russia
Received May 22, 2000
Abstract A series of acetylated aryl -D-glucopyranosides were prepared in 12 63% yields from tetra-O-
acetyl- -D-glycopyranosyl bromide and phenols containing acyl, formyl, and hydroxy substituents, and also
from sterically hindered phenols in the two-phase system chloroform aqueous alkali in the presence of trieth-
ylbenzylammonium chloride. Hydroxyethylated sucrose and dibenzo-18-crown-6 do not behave as phase-
transfer catalysts in glycosylation of phenols.
One of the main routes to acetylated 1,2-trans-
glycosides is the Koenigs Knorr procedure based on
the reaction of appropriate 1,2-cis-halo derivatives of
protected sugars (mainly bromides) with phenols in
solution of an alkali in aqueous acetone [2]. The reac-
tion is accompanied by inversion of the glycoside
center configuration and yields exclusively 1,2-trans
isomers. In several studies, glycosylation of phenols
with bromo derivatives of benzylated and acetylated
sugars was performed with phase-transfer catalysts
[3 7]. Such a modification of the Koenigs Knorr
procedure allows not only synthesis of known
1,2-trans-arylglucopyranosides in high yields, but also
preparation of previously unknown derivatives. Fur-
thermore, the synthesis and workup procedure is
very simple.
Lewis acids (p-toluenesulfonic, sulfuric, and ortho-
phosphoric acids, tin tetrachloride, zinc chloride, etc.)
failed also.
Low yields of aryl glycosides prepared by the
Koenigs Knorr reaction of bromide I with phenols are
probably due to degradation of I in aqueous acetone
under the action of alkalis and lability of phenols
with oxygen-containing substituents under the reac-
tion conditions.
In this connection, we examined the possibility of
preparing glycosides of some natural phenols by the
Koenigs Knorr reaction using phase-transfer catalysts:
OR
O
O
cat.
+ ROH + KOH
+ KBr + H2O.
II
Proceeding with studies on synthesis of arylglyco-
sides, we faced serious problems with glycosyla-
tion of complex and sterically hindered phenols with
tetra-O-acetyl- -acetyl- -D-glucopyranosyl bromide I
under classical conditions of the Koenigs Knorr reac-
tion. Phenols with acyl, formyl, and hydroxymethyl
substituents, as well as phenols with other hydroxyl-
containing substituents and phenols containing o-sub-
stituents in the aromatic ring, did not react with -ace-
tylbromoglucose I, and only in a few cases the corre-
sponding acetylated aryl -D-glucopyranosides were
isolated in very low yields. Our attempts to prepare
glycosides of complex and sterically hindered phenols
by their glycosylation with full acetates of sugars
(Helferich reaction) in the presence of Brønsted and
Br
OAc
OAc
III
I
R is substituted phenyl; cat. is phase-transfer catalyst.
The initial tetra-O-acetyl- -D-glucopyranosyl bro-
mide I was prepared by treatment of penta-O-acetyl-
- and -D-glucopyranose with a solution of hydro-
gen bromide in glacial acetic acid [8]. Because of in-
stability of I, it was stored for no more than 1 2 days
in a vacuum desiccator in the dark. As phase-transfer
catalysts we tested hydroxyethylated sucrose IV,
dibenzo-18-crown-6 V, and triethylbenzylammonium
chloride VI. Hydroxyethylated sucrose containing
seven hydroxyethyl groups per hydroxy group of
sucrose was prepared by treatment of sucrose with
oxirane in dimethyl sulfoxide [9]. Triethylbenzyl-
1
For communication III, see [1].
1070-3632/01/7111-1811$25.00 2001 MAIK Nauka/Interperiodica

1812
PAVLOV et al.
Table 1. Aryl tetra-O-acetyl- -D-glucopyranosides
[ ]2D0
Found, %
Calculated, %
Comp.
no.
Yield,
%
mp,
C
Aryl
Formula
(c 1, CHCl3),
deg
C
H
C
H
IIIa
IIIb
IIIc
IIId
4-Acetylphenyl
42
44
12
63
168 169
158 159
164 165
158 159
27
13
9.5
38.5
56.49
57.19
57.28
58.20
5.41
5.68
5.84
6.58
C22H26O11 56.65
C23H28O11 57.50
C23H28O11 57.50
C24H30O12 56.47
5.65
5.87
5.87
5.92
4-Propionylphenyl
2-Propionylphenyl
2-Methoxy-4-propionyl-
phenyl
IIIe
IIIf
2-Formylphenyl
2-Methoxy-5-formyl-
phenyl
35
50
138 139
140 141
29
25
54.97
55.45
5.35
5.67
C21H23O11 55.75
C22H25O12 54.77
5.35
5.43
IIIg
IIIh
4-Hydroxymethylphenyl
4-(1-Hydroxypropyl)-
2-methoxyphenyl
2,6-Dimethylphenyl
39
35
168 169
12
5.5
54.83
53.98
5.79
6.08
C21H25O11 55.50
C24H32O12 56.24
5.77
6.29
a
IIIi
25
91 92
0
54.58
6.02
C22H28O10 58.40
6.24
a
Syrupy substance.
ammonium chloride was prepared from benzyl chlo-
ride and triethylamine [10].
methanol [2]. The product purity was confirmed by
elemental analysis, optical rotation, and 13C NMR
spectroscopy (Tables 1 3).
The catalytic activity of IV and V in glycosylation
was tested using as an example the reaction of I with
4-acetylphenol IIa in the system acetone solid KOH
at room temperature. The reaction completion was
judged from attainment of the constant optical rotation
angle of the reaction mixture. We found that the reac-
tion is complete in approximately 45 h, giving 4-ace-
tylphenyl tetra-O-acetyl- -D-glucopyranoside IIIa in
7 13% yield depending on the initial amount of the
catalyst. In the absence of IV and V, the results were
similar.
By the example of the reactions of bromide I with
4-hydroxymethylphenol IIg and 4-(1-hydroxypropyl)-
2-methoxyphenol IIh, we demonstrated that glycosyla-
tion in the presence of triethylbenzylammonium chlo-
ride involves exclusively phenolic hydroxyl, yielding
aryl glycosides IIIg and IIIh. The alcoholic hydroxyl
is not involved. Furthermore, alcoholic hydroxyl is
not involved even in attempted glycosylation with I
of a compound containing no phenolic hydroxyl,
1-(3,4-dimethoxyphenyl)-1-propanol.
The pattern was quite different when the reaction
was performed in the system chloroform aqueous
KOH in the presence of triethylbenzylammonium
chloride. Preliminary experiments with varied initial
amounts of reactants and catalyst VI showed that the
highest yields of the target product III are attained
with the molar ratio of phenol, -acetylbromoglu-
cose I, and triethylbenzylammonium chloride of
2 : 1 : 1. This ratio is close to that used by Dess et al.
[6] in syntheses of glycosides of the simplest phenols.
For example, we prepared glycoside IIIa in 42% yield
by refluxing the reaction mixture for 3 h. Glycosy-
lations of other phenols containing acyl, methoxy,
formyl, and hydroxyalkyl substituents in various
positions of the benzene ring, and also of sterically
hindered phenols are complete in 3 5 h. Thus, we
prepared various acetylated aryl -D-glucopyranosides
IIIa IIIi in 12 63% yields (Table 1). Unprotected
aryl -D-glucopyranosides VIIa VIIg were prepared
by Zemplén deacetylation of the corresponding ace-
tates with catalytic amounts of sodium methylate in
Our experimental data allowed evaluation of the
relative effect of various substituents in the aromatic
ring on the reactivity of phenols in glycosylation.
It is seen that o-formyl and especially o-acyl substit-
uents decrease the reactivity of phenols and the yield
of the target products. The p- and m-substituents af-
fect the yields of acetylated aryl -D-glucopyranosides
insignificantly (Table 1).
Thus, the reactivity of phenols in phase-transfer
glycosylation with bromide I is determined by the
presence and nature of oxygen-containing substituents
in the o-position of the phenyl ring. This conclusion
is consistent with Tulvitie’s data [7]; however, we
cannot agree with Tulvitie’s statement that the sug-
gested procedure is inapplicable to synthesis of glyco-
sidues of sterically hindered phenols, as we managed
to prepare 2,6-dimethylphenyl tetra-O-acetyl- -D-gly-
copyranoside in 25% yield. Our results, along with the
data of Klein et al. [11] who prepared acetylated aryl
-D-galactopyranosides by phase-transfer glycosyla-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 11 2001

STRUCTURE AND REACTIVITY OF GLYCOSIDES: IV.
Table 2. Aryl -D-glucopyranosides
1813
[ ]2D0 (c 1,
pyridine),
deg
Electronic spectrum Found, %
max, nm log
Calculated, %
Comp.
no.
Yield,
%
mp,
C
Aryl
Formula
C
H
C
H
max
VIIa
VIIb
VIId
4-Acetylphenyl
56 188 189
77 162 163
89 175 176
32
30
34
214,
264
214,
263
223,
265,
300
210,
253,
310
226,
276,
300 sh
249
4.032, 56.61 6.10 C14H18O7 56.37 6.08
4.184
4-Propionyl-
phenyl
2-Methoxy-4-
propionylphenyl
3.967, 55.85 6.23 C15H20O7 57.69 6.45
4.180
4.180, 54.44 6.79 C16H22O8 56.14 6.48
4.042,
3.787
VIIe
VIIf
2-Formylphenyl 62 185 186
19
21
4.233, 52.78 6.04 C13H16O7 54.93 5.67
4.024,
3.531
2-Methoxy-5-
formylphenyl
64 174 175
4.194, 50.63 5.66 C14H18O8 53.50 5.77
4.075,
3.978
4.140
VIIg
VIIh
4-Hydroxymeth- 70 169 170
ylphenyl
4-(1-Hydroxy-
propyl)-2-meth-
oxyphenyl
17.5
+55
51.13 6.20 C13H18O7 54.54 6.34
61.17 7.68 C16H24O8 56.81 7.02
15 182 183
Table 3. 13C NMR spectra of acetylated and unprotected aryl -D-glucopyranosides ( C, ppm)
Carbohydrate moiety
Aromatic ring
C3 C4
Comp.
no.
Other
signals
C1
C2 C3 C4 C5 C6 CH3
CO
C1
C2
C5
C6
IIIa
IIIb
98.0 70.9 72.1 68.1 72.4 61.8 20.3 170.1, 169.8, 160.1 116.2 130.2 132.3 130.2 116.2 26.1 (CH3)
169.1, 168.9
98.0 70.9 72.0 68.0 72.9 61.7 20.2 170.1, 169.7, 159.8 116.2 129.7 134.0 129.7 116.2 31.2 (CH2),
169.0, 168.8
8.0 (CH3),
198.9 (CO)
IIId
99.5 70.8 71.8 68.1 72.1 61.6 20.1 169.9, 168.9, 149.7 150.1 115.6 132.9 121.4 117.7 55.8 (OCH3),
168.9, 168.7
31.1 (CH2),
8.1 (CH3),
198.9 (CO)
IIIe
IIIf
99.0 70.9 72.1 68.1 72.3 61.7 20.3 170.3, 169.8, 158.6 126.6 128.1 123.4 135.4 116.0 188.8
169.1, 168.9 (CHO)
99.9 70.9 72.1 68.3 72.3 61.9 20.3 170.3, 169.8, 146.4 155.4 111.7 128.4 129.9 117.4 56.0
169.2, 168.9
(OCH3),
189.9
(CHO)
IIIg
IIIh
98.0 70.9 72.0 68.1 72.4 61.8 20.3 170.1, 169.8 160.0 116.0 131.3 124.8 131.3 116.0 51.7
169.1, 168.9
(CH2)
100.6 71.1 71.7 68.4 72.5 61.8 20.2 170.4, 170.0, 144.9 150.4 110.1 134.7 119.8 118.3 55.9
169.2
(OCH3),
130.2
( -CH),
125.0
( -CH), 16.1
(CH3)
IIIi
VIIa
101.3 71.5 71.7 68.5 72.9 61.6 20.1 170.1, 168.1 152.6 127.4 128.9 124.8 128.9 127.4 16.6 (CH3)
99.9 73.3 76.7 69.8 77.8 60.8
161.3 116.1 130.2 131.1 130.2 116.1 26.7 (CH3),
196.7 (CO)
161.3 116.2 130.2 130.9 130.2 116.2 8.5 (CH3),
31.2 (CH2),
VIIb
100.2 73.5 76.8 69.9 77.4 61.0
199.4 (CO)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 11 2001

1814
PAVLOV et al.
tion of phenols with tetra-O-acetyl- -D-galactopyra-
nosyl bromide, demonstrate wide prospects for using
this modification of the Koenigs Knorr procedure for
preparing glycosides of various phenols.
Aryl -D-glucopyranosides VIIa VIIh. A 5-mmol
portion of appropriate acetylated aryl -D-gluco-
pyranoside was suspended in 10 ml of absolute meth-
anol, and 1 ml of a 1 M NaOMe solution in absolute
methanol was added. The deacetylated product started
to crystallize within 10 15 min. The mixture was left
overnight in a refrigerator, and the crystals were fil-
tered off, washed with methanol (1 30 ml), and
vacuum-dried at 60 C.
EXPERIMENTAL
The 13C NMR spectra of acetylated aryl glycosides
were recorded on a Varian CFT-20 spectrometer with
50% solutions in CDCl3, and those of the unprotected
compounds, with solutions in (CD3)2SO. The internal
reference was TMS. The electronic absorption spectra
of aryl- -D-glycopyranosides were recorded on an
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 11 2001