Crystal structure of 1,2;5,6-di-O-isopropylidene-3-O-(phenylacetyl)-D- glucofuranose

Article abstract of DOI:10.1023/A:1024234231567

The synthesis and X-ray crystal structure of 1,2;5,6-di-O-isopropylidene-3- O-(phenylacetyl)-D-glucofuranose is reported. It crystallizes in the orthorhombic system with space group P2₁2₁2₁ (No. 19); a = 9.9313(12) A, b = 10.0657(12) A, c = 20.343(2) A, and Z = 4. The solid state structure is discussed in terms of the use of the title compound for further chemistry.

Full text of DOI:10.1023/A:1024234231567

C
Journal of Chemical Crystallography, Vol. 33, Nos. 5/6, June 2003 ( 2003)
Crystal structure of 1,2;5,6-di-O-isopropylidene-3-O-
(phenylacetyl)-D-glucofuranose
Justin Sheville,(1) Daniel Berndt,(1) Timothy Wagner,(1) and Peter Norris(1)
Received August 2, 2002
The synthesis and X-ray crystal structure of 1,2;5,6-di-O-isopropylidene-3-O-
(phenylacetyl)-D-glucofuranose is reported. It crystallizes in the orthorhombic system with
˚
˚
˚
space group P212121 (No. 19); a = 9.9313(12) A, b = 10.0657(12) A, c = 20.343(2) A,
and Z = 4. The solid state structure is discussed in terms of the use of the title compound
for further chemistry.
KEY WORDS: C20H26O7; carbohydrate; ester.
Introduction
and structure of 1,2;5,6-di-O-isopropylidene-3-
O-(phenylacetyl)-D-glucofuranose, 2, and the im-
plications of the solid state structure on further
chemistry.
Abundant D-glucose has been used for many
years as an affordable, optically pure starting ma-
terialfororganicsynthesis1 andmanyofitsderiva-
tives have become commercially available. One
such compound, 1,2;5,6-di-O-isopropylidene-D-
glucofuranose (commonly known as “diacetone
glucose,” 1, Scheme 1) has a singularly unpro-
tected secondary hydroxyl group at C-3, which
serves as a point for selective functionalization
upon the D-glucose skeleton.
Experimental
Synthesis
In order to attach a carbene precur-
sor, O-3 of compound
1
was coupled
with phenylacetic acid using the common
dicyclohexylcarbodiimide/N,N-dimethylamino-
pyridine (DCC/DMAP) protocol to afford the
ester 2 as a colorless solid in 90% yield. NMR
spectra of 2 were obtained using a VARIAN
GEMINI 2000 spectrometer, at 400 MHz for 1H
The present work is part of a project cen-
tered on the use of carbohydrates as building
blocks for making chiral heterocycles and car-
bocycles, by applying carbenic and nitrenic reac-
---
---
tions for construction of C C bonds and C N
bonds, respectively. Accordingly, we have pre-
pared diazoester and acyl azide derivatives of 1
and then studied their decomposition chemistry.2
Herein we focus specifically on the synthesis
1
and 100 MHz for 13C: H NMR (CDCl3) 1.25
(s, 3H), 1.28 (s, 3H), 1.38 (s, 3H), 1.5 (s, 3H), 3.6
(s, 2H), 3.95 (dd, 1H, J = 5.3, 8.6 Hz), 3.99 (d,
1H, J = 5.9, 8.6 Hz), 4.08 (ddd, 1H, J = 5.3,
5.9, 8.1 Hz), 4.18 (dd, 1H, J = 2.9, 8.1 Hz), 4.42
(d, 1H, J = 3.8 Hz), 5.27 (d, 1H, J = 2.9 Hz),
5.81 (d, 1H, J = 3.7 Hz), 7.25–7.55 (m, 5H).
13C NMR (CDCl3) 25.2, 26.2, 26.8, 26.9, 41.4,
(1) Department of Chemistry, Youngstown State University,
Youngstown, Ohio 44555.
Towhomcorrespondenceshouldbeaddressed. E-mail:trwagner@
cc.ysu.edu
409
C
1074-1542/03/0600-0409/0 2003 Plenum Publishing Corporation

410
Sheville, Berndt, Wagner, and Norris
Scheme 1.
67.2, 72.2, 76.3, 79.8, 83.1, 104.9, 109.2, 112.2,
127.1, 128.5 (double intensity), 129.0 (double
intensity), 133.2, 169.8. MS: Calculated: 378.42.
Found (APCI, positive mode): 379.27 (M+H+).
solvent mixture, compound 2 was collected as
colorless crystals that were suitable for analy-
sis by X-ray diffraction. X-ray data were col-
lected on a Bruker SMART APEX 4k CCD
Single Crystal Diffractometer equipped with a
normal focus, 2.4 kW sealed tube X-ray source
Crystal structure determination
(graphite monochromatized Mo K radiation,
0.71073 A) operating at 50 kV and 40 mA. The
=
˚
Upon crystallization by slow evaporation of
a 50:50% by volume ethyl acetate and hexane
diffraction data were obtained by collection of
Table 1. Crystal Data Summary and Refinement Results for 2
Structural formula
CCDC deposit no.
Formula weight
Color/shape
Crystal size, mm
Crystal system
Space group
C20H26O7
201732
378.41
Colorless/rectangular prism
0.48 0.24 0.18
Orthorhombic
P212121 (No. 19)
Unit cell dimensions
˚
a = 9.9313(12) A
˚
b = 10.0657(12) A
˚
c = 20.343(2) A
˚
V = 2033.6(4) A
Z
4
calc, g/cm3
Temperature, K
1.236
298(2)
0.71073
0.093
˚
(Mo K ), A
, mm
1
Range for data collection (deg)
Limiting indices
2.00–28.27
12
h
12, 12
k
12, 26
l
25
No. of reflections collected
No. of independent reflections
No. of parameters
17652
4711 (Rint = 0.0230)
324
Refinement method
Full-matrix least squares on F2
Hydrogen atom positions
Final R indices [I > 2 (I)]
Final R indices (all data)
Goodness-of-fit on F2
Mixed independent and constrained refinement
R1(F)a = 0.0637, wR2(F2)b = 0.1612
R1(F)a = 0.0754, wR2(F2)b = 0.1696
1.157
Absolute structure parameter
Largest diff. Peak and hole
0.6(12)
0.289 and -0.188 e A
3
˚
a R1(F) = 6||Fo| |Fc||/6|Fo| with Fo > 4.0 (F).
1
2
bwR2(F2) = [6[w(Fo2 Fc2)2]/6[w(Fo2)2]]1/2 with Fo > 4.0 (F), and
w
=
(Fo)2 + (W P)2 + T P, where P = (Max(Fo2, 0) + 2Fc2)/3, W = 0.0945, and T =
0.12.

Crystal structure of 1,2;5,6-di-O-isopropylidene-3-O-(phenylacetyl)-D-glucofuranose
411
Table 2. Atomic Coordinates (104) and Equivalent Isotropic
606 frames at each of three ϕ settings, 0 , 120 ,
and 240 , using a scan width of 0.3 in ω. At the
end of the data collection, 50 initial frames were
recollected to monitor crystal decay. The exposure
time was 10 s/frame.
The initial unit cell parameters were deter-
mined in Bruker’s SMART3 program from 999
reflections, whichwereharvestedfrom380frames
3
2
˚
Displacement Parameters (10 A ) for 2
a
x
y
z
Ueq
O(1)
O(2)
O(3)
O(4)
9144(2)
7603(2)
4838(2)
7611(2)
5348(2)
6220(20)
6480(20)
3266(2)
7894(2)
6857(2)
5908(2)
6791(2)
6097(3)
7038(4)
5362(3)
3980(30)
4140(20)
5353(15)
6102(16)
8970(2)
9854(3)
9210(4)
3557(2)
2583(3)
2324(2)
3209(3)
2975(4)
1843(4)
969(4)
8017(2)
8821(2)
8137(2)
8326(2)
11060(2)
11215(17)
11587(18)
9445(3)
7623(3)
8048(2)
8957(2)
9438(3)
9906(3)
10376(5)
11885(3)
11600(40)
11910(40)
13378(11)
13129(13)
8407(3)
9585(4)
7218(4)
8487(3)
7532(3)
7893(2)
7546(3)
7919(4)
8626(4)
8981(4)
8622(3)
2420(1)
3124(1)
2040(1)
1578(1)
1276(1)
241(12)
345(12)
2484(1)
2158(1)
2671(1)
2297(1)
1745(1)
1126(1)
584(2)
68(1)
58(1)
54(1)
62(1)
72(1)
83(3)
83(3)
91(1)
54(1)
50(1)
47(1)
52(1)
59(1)
79(1)
72(1)
130(6)
130(6)
113(3)
113(3)
61(1)
95(1)
90(1)
54(1)
63(1)
57(1)
73(1)
83(1)
81(1)
80(1)
69(1)
O(5)
O(6A)
O(6B)
O(7)
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
for a minimum threshold of I/
5.0. These
parameters were then used to integrate all the
data in Bruker’s SAINT4 program, where global
refinement of the unit cell parameters was also
performed to give the final values utilized in the
subsequent structural analysis. Prior to structure
solution and refinement, the data files written by
SAINT were processed through SADABS5 for
correction of errors due to absorption by the glass
capillary, crystal decay, and other effects.
The structure was solved via direct methods
using the SHELXS6 program, and refined via full-
matrix least squares against F2 on all data using
SHELXL.6 Structure plots that appear in this pa-
per were obtained from the program SHELXP.6
Positions for all non-hydrogen atoms were refined
anisotropically. This was followed by isotropic
refinement of all hydrogen positions, except for
those on the four methyl groups in the molecu-
lar unit. For two of these methyl-carbons, hydro-
gen positions were not assigned (discussed later),
while for the other two [i.e. C(11) and C(12)],
the hydrogen atoms were refined using a riding
model. The absolute structure could not be de-
termined reliably because of the absence of sig-
nificant anomalous scatterers in the sample, al-
though it was taken to be correct on the basis of
the NMR data. Refinement data are summarized
in Table 1 and atomic coordinates and equivalent
isotropic displacement parameters are listed in
Table 2.
C(7)
709(1)
253(8)
450(7)
917(7)
C(8A)
C(8B)
C(9A)
C(9B)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
C(19)
C(20)
945(8)
3090(1)
3237(2)
3528(2)
2181(1)
1869(2)
1161(1)
669(2)
24(2)
128(2)
349(2)
998(2)
1186(3)
aU(eq) is defined as one third of the trace of the orthogonalized U
ij
tensor.
C(3), respectively], which is a feature often seen
in derivatives of 1. Despite these protons being
vicinal they do not couple; a consequence of the
90 dihedral angle that is reinforced by the crys-
tal structure of 2, shown in Fig. 1, in which this
relationship is clearly seen in the solid state.
The major feature of note during the course
of the refinement was the observation of relatively
high equivalent isotropic atomic displacement pa-
rameters at the O(6), C(8), and C(9) positions.
Each of these atoms had large enough anisotropic
displacement along one direction such that they
couldbesplitbetweentwopositions(0.502, 0.537,
Results and discussion
1
The H NMR spectrum of 2 contained all
˚
of the expected signals including 1-H doublets
for H(2) and H(3) [attached to carbons C(2) and
and 0.787 A apart, respectively), presumably re-
flecting the greater flexibility of the dioxolane ring

412
Sheville, Berndt, Wagner, and Norris
The carbene (or carbenoid) that would form at
the alpha-carbon of the phenacyl group (C(14) in
---
Fig. 1) would have three major C H insertion
---
pathways open to it; either into the C(1) H(1)
---
---
bond, the C(2) H(2) bond, or the C(5) H(5)
bond. In this case the preference was for five-
membered ring formation via insertion into the
2
---
C(2) H(2) bond.
Acknowledgments
PN acknowledges support from the American
Chemical Society Petroleum Research Fund. Purchase
of the CCD X-ray diffractometer at Youngstown State
was supported through funding from NSF-CCLI Grant
no. 0087210 and the Ohio Board of Regents Action
Fund, Grant no. CAP-491.
Fig. 1. Molecular structure of 2, with displacement ellipsoids
at the 40% probability level. Hydrogen atoms are drawn as
circles with an abritrary radius. Only one of the split-atom
pairs at each of the O(6), C(8), and C(9) positions are shown
for clarity.
References
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tached at C(1) and C(2). The split positions are
labeled as O(6A) and O(6B), C(8A) and C(8B),
and C(9A) and C(9B) in Table 2. Because of the
disorder, the six hydrogen atoms connected to the
C(8) and C(9) methyl carbons were not assigned.
The crystal structure results embodied in
Fig. 1 illustrates nicely the thinking behind the
use of derivatives of 1 in our initial studies of
diazo decomposition on carbohydrate platforms.
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