Synthesis and structure of 2-pyransoylperimidines

Article abstract of DOI:10.1016/j.carres.2010.09.028

The first examples of 2-pyranosylperimidines are reported. The β-d-glucopyranosyl nitrile oxide 5, generated by base-induced dehydrochlorination of the hydroximoyl chloride 4, reacted with 1,8-diaminonaphthalene to afford the 2-(β-d-glucopyranosyl)perimid

Full text of DOI:10.1016/j.carres.2010.09.028

Carbohydrate Research 346 (2011) 43–49
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Synthesis and structure of 2-pyransoylperimidines
⇑
Iain A. S. Smellie, Andreas Fromm, Stephen A. Moggach, R. Michael Paton
School of Chemistry, The University of Edinburgh, King’s Buildings, West Mains Road, Edinburgh EH9 3JJ, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 25 July 2010
Received in revised form 17 September
The first examples of 2-pyranosylperimidines are reported. The b-D-glucopyranosyl nitrile oxide 5,
generated by base-induced dehydrochlorination of the hydroximoyl chloride 4, reacted with 1,8-diami-
nonaphthalene to afford the 2-(b- -glucopyranosyl)perimidine 8. The -xylo-, -galacto-, -manno- and
-glycero analogues 12, 15, 16 and 19 were prepared similarly. The glycals 9 and 13 were formed as
by-products resulting from elimination of acetic acid from the corresponding pyranosylperimidines.
The structure of -glucose-derived perimidine 8 was established by X-ray crystallography.
Ó 2010 Elsevier Ltd. All rights reserved.
D
D
D
D
2
010
D
Accepted 23 September 2010
Available online 16 October 2010
D
Keywords:
Perimidines
Nitrile oxides
C-Glycosides
X-ray crystallography
1
. Introduction
therefore have the characteristics of both
p
-deficient and
p-excessive
1
7,18
systems.
applications ranging from dyestuffs
Perimidines and their derivatives have found a variety of
to fluorescent molecular sen-
sors. Their biological activity has also been examined, for example as
1
6,19
There is increasing interest in developing methods for the syn-
thesis of pyranosyl-substituted heterocycles1 in view of their po-
tential biological activity. Recent examples include pyranosyl
oxadiazoles,
dazoles,
glycogen phosphorylase inhibitors. Most routes to benzimidazoles
involve acid-catalysed cyclocondensation of 1,2-diaminobenzene
–14
20
1
6
antiulcer, antimicrobial and antifungal agents. The DNA-binding
properties and antitumour activity of various perimidines have been
1
–3
1,2,5,6
1,2,5,7
tetrazoles,
benzothiazoles
and benzimi-
2
,5,7,8
21
which have been shown to act as glycosidase and/or
studied, as have the thermochromic properties and EPR spectra of
2
0,22,23
perimidine (diazaphenalenyl) radicals.
a
The pK value of perimi-
dine (6.02) lies between those of imidazole (7.10) and benzimidazole
(5.49) and its potential as a nucleophilic catalyst, for example for ester
(
DAB) with carboxylic acids or their derivatives, or reaction with
2
4
aldehydes followed by oxidation of the resulting benzimidazo-
hydrolysis, has attracted attention. Perimidines are also useful start-
ing materials for the synthesis of more complex polycyclic heterocy-
lines.9 Some time ago, however, it was established
,10
11–13
that 2-aryl
1
6,25–27
0
benzimidazoles could also be prepared from nitrile oxides and DAB,
and we have recently reported14 that this approach can be used for
the synthesis of 2-pyranosylbenzimidazoles from pyranosyl nitrile
oxides (Scheme 1). We now describe the results of an investigation
into the corresponding reaction of pyranosyl nitrile oxides with
cles.
N,N -Diisopropylperimidine provides the core of a novel
28
N-heterocyclic carbene ligand.
The spacial arrangement of the two amino groups in 1,8-diami-
nonaphthalene (DAN) is similar to that in 1,2-diaminobenzene and
most synthetic approaches to perimidines are therefore, by anal-
ogy with benzimidazole synthesis, based on reaction of DAN with
a one-carbon unit, usually a carbonyl-containing compound. For
example, carboxylic acids, acyl halides and anhydrides afford the
1
,8-diaminonaphthalene (DAN) as
a
potential route to
15
pyranosylperimidines.
Perimidines (1) are peri-naphtho-fused derivatives of pyrimidine
and are of particular interest as they are a rare example of an azine in
which the lone pair of electrons of a pyrrole-like nitrogen participates
1
6,29–31
mono-amide derivatives 2,
which can be converted into 1
by acid-catalysed cyclisation. Aldehydes react with DAN to form
in the
p
-system of the molecule. Perimidine has 14
p
-electrons, is iso-
dihydroperimidines 3 that can readily be dehydrogenated to yield
1
6,29,32–36
electronic with the phenalenyl anion, and there is some transfer of
electron density from the heterocycle to the naphthalene ring. They
1.
Perimidines have also been prepared from 1-amido-8-
1
6
37
38
azidonaphthalenes, by reaction of DAN with 1,3,5-triazine,
3
9
and from
a-amido-a-aminonitones. These methods allow for
the preparation of perimidines bearing a range of substituents at
the 2-position including alkyl, aryl, heterocycles, halogens and
amines, but until the present work there have been no reported
examples of pyranosyl-substituted perimidines.
⇑
Corresponding author. Fax: +44 131 650 4743.
E-mail address: R.M.Paton@ed.ac.uk (R.M. Paton).
Alternative names include: 1H-benzo[de]quinazoline; 1H-naphtho[1,8-de]pyrim-
idine; 1H-1,3-diazaphenalene.
0
008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.09.028

4
4
I. A. S. Smellie et al. / Carbohydrate Research 346 (2011) 43–49
RO
RO
RO
H
N
O
H
2
N
O
N O
+
RO
RO
H N
2
N
RO
OR
OR
Scheme 1.
4
CuSO , which we find to be an effective means of removing unre-
acted DAN. 2-Phenylperimidine was isolated (68%) as an orange
R
R
R
O
NH2
solid and identified by comparison of its physical and spectro-
N
NH
NH2 NH2
HN
HN
NH
scopic properties with those reported in the literature.4
2,43
Reac-
tion of the anthracene nitrile oxide with DAN afforded the
4
2
corresponding perimidine (1, R = 9-anthryl) in low yield (30%),
but the product could not be isolated in a pure state. The proposed
reaction mechanism is outlined in Scheme 3. Initial dehydrochlori-
nation of the hydroximoyl chloride by DAN acting as a base gener-
ates the nitrile oxide 6, which is then subject to nucleophilic
addition by one of the amino groups of a second molecule of
DAN to form the mono-amidoxime 7. Subsequent cyclisation with
elimination of hydroxylamine yields the perimidine 1. An alterna-
tive pathway to amidoxime 7 involving nucleophilic addition of
the amine to the C@N of the hydroximoyl chloride, followed by
elimination of HCl, cannot be excluded. However, for the corre-
sponding reaction of hydroximoyl chlorides with aniline itself
affording Z-amidoximes, the pathway via the nitrile oxide is
1
DAN
2
3
2
. Results and discussion
The key step in the synthetic route to the pyranosylperimidines
1, R = pyranosyl) involves reaction of DAN with a pyranosyl nitrile
oxide. As nitrile oxides are generally short-lived and are prone to
dimerisation to furoxans (1,2,5-oxadiazole N-oxides) they are usu-
ally generated in situ in the presence of the co-reactant, either by
(
4
1b
favoured.
base-induced dehydrohalogenation of hydroximoyl halides or by
dehydration of nitromethyl compounds.40 We have previously re-
Having demonstrated that simple aryl perimidines could be
prepared by combination of a nitrile oxide and DAN, the potential
of this method for the synthesis carbohydrate-substituted ana-
ported that pyranosyl hydroximoyl chlorides can be prepared from
the parent aldose via the pyranosylnitromethane derivative as
logues was investigated, using D-glucose-derived nitrile oxide 5
illustrated in Scheme 2 for the D-glucopyranosyl hydroximoyl chlo-
4
1
as an example. Heating a solution of hydroximoyl chloride 4 and
DAN (1:2.5 molar ratio) in ethanol at reflux for 5 h, followed by
work-up as described above for benzohydroximoyl chloride, affor-
ded a mixture of two products that were separated by chromatog-
raphy. The more polar compound was identified from its
ride 4, and these precursors were therefore used in the present
work. The pyranosyl nitrile oxide 5 is then generated by treatment
of 4 with base.
Before attempting to synthesise pyranosyl perimidines the
method was first tested for the known 2-phenylperimidine
1, R = Ph)
by reaction of DAN with, respectively, benzonitrile oxide (gener-
ated from benzohydroximoyl chloride ) and anthracene-9-carbo-
nitrile oxide; the latter nitrile oxide can be isolated and does not
require in situ generation. solution of benzohydroximoyl
chloride and DAN (1:2 molar ratio) in ethanol was heated at reflux
for 5 h. Work-up of the reaction mixture included washing with aq
2
9,30,42,43
42
spectroscopic properties as the
(
had characteristic peaks for the perimidine moiety (Table 2) in
addition to those expected for the tetra-O-acetylglucopyranosyl
substituent, vide infra. The mass spectrum showed the required
D
-glucopyranosyl-perimidine 8
(
and 2-(9-anthryl)perimidine (1, R = 9-anthryl)
16%) (Table 1, entry 2). Its H and 13C NMR spectra in DMSO-d
1
6
42
44
4
5
A
+
molecular ion peak at m/z 499 [M+1] . The less polar product
(
34%) was assigned the corresponding glucal-perimidine structure
9. In contrast to 8, only three acetate groups were detected in the
AcO
AcO
AcO
AcO
AcO
O
NO2 (i) [H]
ii) Cl2
O
NOH
Cl
O
base
- HCl
D-Glc
AcO
AcO
AcO
AcO
N O
(
OAc
OAc
OAc
4
5
Scheme 2.
R
R
NOH
NH2
HN
N
NH
R
DAN
DAN
- NH OH
2
NOH
R
N O
-
HCl
Cl
6
7
1
Scheme 3.

I. A. S. Smellie et al. / Carbohydrate Research 346 (2011) 43–49
45
Table 1
Formation of 2-substituted perimidines
Entry
RCCl@NOH
Conditionsa
Pyranosyl-perimidine
Glycal-perimidineb
Product ratioc
1
2
PhCCl@NOH
A
A
1 R = Ph (68%)
8 (16%)
—
—
1:2.12
D
D
D
D
D
D
D
-Glc (4)
9 (34%)
3
4
5
6
7
8
9
-Glc (4)
B
A
B
B
B
A
A
8 (65%)
9 (Trace)
13 (43%)
13 (Trace)
—
—
-Xyl (11)
-Xyl (11)
-Gal (14)
-Man (17)
-Man (17)
12 (16%)
12 (60%)
15 (69%)
16 (55%)
16 (4%)
1:3.17
—
—
9 (Trace)
9 (34%)
—
—
1:8.50
—
18
19 (61%)
a
b
c
(
2
A) 5 h, reflux; (B) 15 h, room temperature.
-(2-Deoxy-1-enopyranosyl)perimidines.
Ratio of pyranosyl-perimidine to glycal-perimidine (8:9, 12:13, 16:9).
NMR spectra and there was no signal in the anomeric proton
region; in addition to the perimidine signals, there were also
pyranosyl-perimidine 12, with only traces of the glycal-perimidine
13 being detected. In contrast, in ethanol at reflux a mixture of 12
and 13 was obtained. The corresponding reaction at room temper-
ature of DAN with the D-galactose-derived hydroximoyl chloride
14 also afforded the expected pyranosyl-perimidine 15 (69%) (Ta-
0
0
distinctive peaks for the glucal carbons C-1 and C-2 at 148.1
and 99.1 ppm, respectively. Its mass spectrum showed the molec-
+
ular ion peak at m/z 439 [M+1] . In an attempt to mimimise the for-
mation of the glucal, the experiment was repeated under less
forcing conditions; after 15 h at room temperature the reaction
was complete (TLC) and the major product (65%) was the target
pyranosyl-perimidine 8 (Table 1, entry 3), with only traces (<1%)
of the glucal 9 being detected. This by-product is believed to result
ble 1, entry 6).
It has been reported that alkyl groups attached to the highly
electrophilic 2-position of perimidene have acidic a
-hydrogens.1
6d
The elimination of acetic acid to form the glycal might therefore
occur via an E1cB mechanism in view of the potential for delocal-
isation of a negative charge at the anomeric position into the adja-
cent perimidine ring system. Deprotonation could occur with
either DAN or the newly-formed perimidine acting as the base;
0
0
from base-catalysed elimination of acetic acid at C-1 /C-2 of the
glucopyranosyl ring forming the glucal in which the alkene unit
is conjugated to the perimidine. There was no evidence for forma-
tion of the 3,4-diglucopyranosyl furoxan 10 that might have re-
a
the pK of DAN is ca. 5, whereas those for 2-substituted perimi-
dines are reported to be ca. 6.
4
1b
16a
sulted from dimerisation of the intermediate nitrile oxide.
It has also been reported that
OAc
AcO
AcO
OAc
O
N
AcO
AcO
AcO
AcO
O
HN
N
O
HN
N
O
O
O
N
AcO
AcO
AcO
OAc
AcO
OAc
8
9
OAc
10
A similar pattern of reactivity was found for the reaction of DAN
with the -xylopyranosyl hydroximoyl chloride 11 (Table 1, entries
and 5). At room temperature the major product (60%) was the
the analogous 2-acetyl-protected glucopyransoyl-benzimidazole
undergoes similar base-induced elimination of HOAc to form the
corresponding glucal. In order to provide more evidence for the
D
5
4
Table 2
Selected 13C NMR chemical shiftsa for 2-substituted perimidines
Compd
C-2
C-3a
C-4
C-5
C-6
C-6a
C-7
C-8
C-9
C-9a
C-9b
1
1
8
9
1
1
1
1
1
ab
b
152.7
153.4
153.8
148.6
154.0
150.1
153.6
153.8
155.5
145.1
145.4
145.7
145.8
145.8
145.9
145.7
145.6
144.3
114.0
113.9
115.3
115.3
115.0
115.2
115.0
114.8
113.4
128.9
129.0
130.3
130.4
130.3
130.4
130.3
130.3
128.5
119.3
119.6
121.3
121.1
121.1
121.0
121.1
120.8
119.0
135.1
135.3
136.6
136.6
136.6
136.6
136.6
136.6
134.9
117.8
118.0
119.3
119.5
119.2
119.5
119.3
119.7
117.6
128.0
128.0
129.5
129.5
129.5
129.5
129.4
129.4
127.7
102.8
102.3
104.0
104.6
104.1
104.7
104.4
104.5
104.5
138.6
138.7
139.3
139.1
139.4
139.2
139.3
139.0
137.5
121.7
121.9
123.5
123.7
123.6
123.8
123.6
123.4
121.8
b
2
3
5
6
9
a
6
ppm in DMSO-d .
b
1
a, 2-phenylperimidine; 1b, 2-(9-anthryl)perimidine; data for 1a and 1b taken from Ref. 42.

4
6
I. A. S. Smellie et al. / Carbohydrate Research 346 (2011) 43–49
O
HN
N
O
DAN
O
D-Mannitol
NOH
O
Cl
1
8
19
Scheme 4.
reaction pathway, an attempt was made to prepare mannopyrano-
syl-perimidine 16. In this case the 2-acetoxy group would be anti-
periplanar to the anomeric hydrogen atom and well placed to
undergo E2 as well as E1cB elimination, and thus be more likely
to form the glycal. Conducting the reaction of DAN with the D-man-
nose-derived hydroximoyl chloride 17 in ethanol at room temper-
ature afforded pyranosyl perimidine 16 (55%) together with traces
of the glycal 9. When the reaction was carried out in refluxing eth-
anol, however, glycal 9 was indeed the dominant product (9 34%,
1
6 4%; 9:16 = 8.5:1). The increased proportion of the glycal perimi-
dine 9 can thus be attributed to the availability of the more
favoured E2 pathway.
Also investigated was the condensation reaction of DAN with
dioxolanyl hydroximoyl chloride 18, which is formally derived
from
by chlorination of 2,3-O-isopropylidene-
which is readily accessible from -mannitol by oxidative cleavage
D-glyceraldehyde. The hydroximoyl chloride 18 was prepared
D-glyceraldehyde oxime,
D
of its 1,2;5,6-diisopropylidene derivative and oximation of the
resulting aldehyde, as reported by Thomas and co-workers.4 Heat-
ing DAN with hydroximoyl chloride 18 in ethanol at reflux for 5 h
6
afforded the
D
-glyceryl-perimidine 19 in 61% yield (Scheme 4).
Figure 1. Crystal structure of glucopyranosyl-perimidine 8.
O
O
AcO
AcO
X
AcO
AcO
X
2-position does not significantly affect the chemical shifts for the
naphthalene portion of the perimidine; only the signal for C-2 itself
is substituent dependent. A notable feature of the C NMR spectra
OAc
13
9
4
8
5
of 2-substituted perimidines is the difference in chemical shift be-
1
1 X = CCl=NOH
2 X = Per
13 X = Per
tween C-4 and C-9 (
glucose-derived perimidine 8 resonate at 115.3 and 104.0 ppm,
respectively. For all the glycosyl-perimidines d = 10–11 ppm,
similar to the values reported by Llamas-Saiz et al. for the 2-phenyl
D
d = dC-4 ꢀ dC-9). For example, C-4 and C-9 of
D-
HN
7
6
1
Per =
2
D
N
AcO
AcO
AcO
AcO
42
1
and 2-(9-anthryl) analogues. Similarly, in the H NMR spectra H-
O
O
4
0
absorbs at higher frequency than H-9 (
.2 ppm).
D
d = dH-4 ꢀ dH-9 = ca.
X
X
The structure of D-glucose-derived perimidine 8 was confirmed
AcO
OAc
AcO
OAc
by X-ray crystallography (Fig. 1). Selected bond lengths and bond
angles for the perimidine ring system are given in Table 3, and
1
4 X = CCl=NOH
5 X = Per
17 X = CCl=NOH
16 X = Per
4
2
are found to be very similar to those reported for the anthryl ana-
1
logue 1 (R = 9-anthryl). The naphthalene unit has similar bond
5
1,52
lengths and angles to those of naphthalene itself.
5
3
The Cremer and Pople puckering parameters for the glucopyr-
anose ring [Q = 0.5756(19) Å, h = 13.54(19)°, = 357.0(9)°] are
comparable with those of the ideal cyclohexane chair
u
Strong supporting evidence for the proposed structures is
1
13
provided by their H and C NMR spectra. Not only do they show
the characteristic features of the peracetylated carbohydrate sub-
stituents, but there is also good correlation between the observed
[
Q = 0.630 Å, h = 0°,
a predominantly
u
= 0°] indicating that, as expected, it adopts
4
C
1
conformation. The proton–proton 1H NMR
couplings for the glucose ring [J
.6 Hz] are also typical of b- -glucopyranosides and are consistent
with the observed H–C–C–H torsion angles from the X-ray data
1 –2 2 –3 3 –4 4 –5
9.7, J 8.9, J 9.5, J
0 0 0 0 0 0 0 0
signals for the perimidine ring system and those reported in the lit-
erature.4
2,43,47
8
D
3
Spectra recorded in CDCl had broad signals in the
aromatic region attributable to amidine-type degenerate tautom-
4
2,43,47–49
0C
0C
0H
0
0C
0C
0H
0
0C
0C
0H
0
[
H
H
1
1
2
2
+172.5°, H
2
2
3
3
ꢀ160.3°, H
3
3
4
4
+159.1°;
erism previously reported for perimidines
that observed for benzimidazoles.50 Repeating the NMR experi-
ments in DMSO-d , however, suppressed the interconversion suffi-
ciently to provide well-resolved aromatic signals; the same effect
and similar to
0C
0C
0H
0
ꢀ174.6°]. The atoms of the perimidine ring system
4
4
5
5
are near planar [maximum deviation 0.0850(17) Å], as are the
atoms N(1), C(2), C(2 ), N(3) linking the pyrimidine part of the per-
6
0
49
imidine to the two pyranosyl substituent. The dihedral angle in the
crystal between the best plane of the perimidine ring system and
was observed by Yavari et al. on cooling below ꢀ60 °C. In Table
1
3
2
6
the perimidine ring C chemical shifts in DMSO-d for the new
42
0
0
0
that made by the atoms C(1 ), C(3 ) and C(5 ) of the pyran ring is
8.79(5)°. The water molecule in the crystal is located adjacent
glycosyl-perimidines are compared with those for the 2-phenyl
and 2-(9-anthryl) analogues. The nature of the substituent at the
6

I. A. S. Smellie et al. / Carbohydrate Research 346 (2011) 43–49
47
Table 3
Selected experimental bond lengths and bond angles for pyranosyl-perimidine 8 and anthryl-perimidine (1 R = 9-anthryl)
a
Length (Å)
8
1 (R = 9-anthryl)
Bond angle (°)
8
1 (R = 9-anthryl)
N(1)–C(2)
1.351(3)
1.396(3)
1.506(3)
1.300(2)
1.410(3)
1.377(3)
1.425(3)
1.409(4)
1.359(4)
1.420(4)
1.423(4)
1.426(3)
1.367(4)
1.412(3)
1.378(3)
1.414(3)
1.352(2)
1.398(2)
1.493(2)
1.301(2)
1.408(2)
1.378(3)
1.416(2)
1.404(3)
1.358(4)
1.416(3)
1.412(3)
1.420(2)
1.355(3)
1.408(3)
1.374(3)
1.412(2)
C(2)–N(1)–C(9a)
N(1)–C(2)–N(3)
121.21(17)
125.57(18)
116.64(16)
117.46(18)
116.94(18)
120.3(2)
120.26(18)
122.8(2)
116.08(18)
119.6(2)
121.9(2)
124.4(2)
115.8(1)
119.7(1)
117.5(1)
120.1(2)
120.8(1)
123.0(2)
116.0(2)
119.4(2)
N(1)–C(9a)
0
0
C(2)–C(1 )
N(1)–C(2)–C(1 )
0
C(2)–N(3)
N(3)–C(3a)
C(3a)–C(4)
C(3a)–C(9b)
C(4)–C(5)
N(3)–C(2)–C(1 )
C(2)–N(3)–C(3a)
N(3)–C(3a)–C(4)
N(3)–C(3a)–C(9b)
N(1)–C(9a)–C(9)
N(1)–C(9a)–C(9b)
C(3a)–C(9b)–C(9a)
C(5)–C(6)
C(6)–C(6a)
C(6a)–C(7)
C(6a)–C(9b)
C(7)–C(8)
C(8)–C(9)
C(9)–C(9a)
C(9a)–C(9b)
a
Data from Ref. 42.
to both N(1)–H of the perimidine and the pyranose ring oxygen,
O(6 ). There are hydrogen bonds between the permidine and the
temperature the colour faded and the products were isolated as
solids by removing the solvent in vacuo and trituration with ice-
0
water molecule [N(1)H(1)ꢁ ꢁ ꢁO(S1)] and between the water mole-
cold Et
was prepared similarly from 2,3-O -isopropylidene-
hyde oxime, which is readily accessible from 1,2;5,6-diisopropylid-
ene- -mannitol by oxidative cleavage followed by oximation of the
2
O. 4R-4-Chloro-oximino-2,2-dimethyl-1,3-dioxolan (18)46
0
0
cule and the ring oxygen O(6 ), [O(1S)H(2S)ꢁ ꢁ ꢁO O(6 ). Both of these
interactions serve to H-bond molecules along the [1 0 0] direction.
There are no other H-bonding interactions.
D-glyceralde-
D
4
6
In conclusion, a short synthetic route to novel glycosyl-perimi-
dines has been developed based on combination of 1,8-diamino-
naphthalenes and readily accessible glycosyl hydroximoyl
chlorides. The key steps in the process are believed to involve ini-
tial base-induced dehydrochlorination of the hydroximoyl chloride
to generate the glycosyl nitrile oxide, followed by nucleophilic
addition of the diaminonaphthalene with loss of hydroxylamine.
In view of the known biological activity of analogous 2-pyran-
osyl-benzimidazoles and of perimidines in general, we consider
that this new class of heterocyclic C-glycosides are worthy of fur-
ther investigation.
resulting aldehyde, as reported in the literature. Benzohydroxi-
moyl chloride was prepared by chlorination of syn-
4
4
benzaldoxime.
3.3. Synthesis of the 2-substituted perimidines
3.3.1. General procedure
The hydroximoyl chloride (1 equiv) and 1,8-diaminonaphtha-
lene (2.5 equiv) were dissolved in EtOH (10 mL) and the mixture
stirred under an atmosphere of nitrogen, either at reflux for 5 h
or at room temperature for 16 h. The reaction mixture was diluted
with CH
CO (50 mL) and then with 4% aq CuSO
cipitate formed. The combined layers were filtered through a pad
of Celite. The organic layer was separated, dried (MgSO ), and the
solvent removed in vacuo. The products were isolated by dry-flash
2
Cl
2
(50 mL), and then washed first with saturated aq
K
2
3
4
(50 mL) until a dark pre-
3
3
. Experimental
.1. General methods and materials
4
chromatography (silica, hexane/Et
2
O, gradient elution).
Melting points were measured on a Gallenkamp capillary tube
apparatus and are uncorrected. Optical rotations were measured
at 21 °C on an Optical Activity Polaar 20 polarimeter using 2 ml
of filtered solution. The 1H and C NMR spectra were recorded
with Varian WP200SY, Brucker AX250 and Brucker avance 360
3
.3.2. 2-Phenylperimidine (1, R = Ph)
4
3b
13
Orange crystalline solid (68%): mp 187–188 °C [lit.
mp 187–
1
1
7
88 °C]; H NMR (CDCl
3
, 250 MHz): d 7.85–7.90 (m, 2H, ArH), 7.47–
.55 (m, 2H, ArH), 7.14–7.26 (m, 4H, ArH), 6.65 (br s, 2H, H-4, H-9);
X
spectrometers. Chemical shifts (d ) are reported in parts per
+
+
EIMS: m/z 244 (M ); HREIMS: Found: M 244.1004, C17
quires M 244.1001.
H
12
N
2
re-
million (ppm) using tetramethylsilane as internal standard. Posi-
tive-ion FAB and high resolution mass spectra were obtained on
a Kratos MS50TC instrument using either glycerol or thioglycerol
matrices. Merck aluminium-backed plates coated with Kieselgel
GF254 silica (0.2 mm) were used for analytical TLC; detection was
+
3
.3.3. 2-(2,3,4,6-Tetra-O-acetyl-b-
D-glucopyranosyl)perimidime
(
8)
2
D
0
Yellow solid (65%): mp 105–106 °C; ½
aꢃ
ꢀ233 (c 0.15, CHCl
3
);
by UV or with a staining solution [P
2
O
5
ꢂ 24MoO
3
ꢂ xH
2
O (10 g),
SO (50 ml)] and heat.
1
R
f
0.18 (Et
2
O); H NMR (CD
3
3
SOCD , 360 MHz): d 10.44 (br s, 1H,
(
NH Ce(NO (5 g), H O (450 ml), and H
4
)
2
3
)
6
2
2
4
NH), 7.21–6.94 (m, 4H, H-5, H-6, H-7, H-8), 6.55 (m, 1H, H-4),
6
Dry flash chromatography was carried out using Kieselgel GF254
and eluted under water pump vacuum.
0
.38 (m, 1H, H-9), 5.45 (dd, 1H, J
3
0
,4
0
9.5, J
3
0
,2
0
8.9 Hz, H-3 ), 5.35
0
(
dd, 1H, J
4
0
,3
0
9.5, J
4
0
,5
0
8.6 Hz, H-4 ), 5.05 (dd, 1H, J
2
0
,1
0
9.7, J
2
0
,3
0
0
0
8
5
.9 Hz, H-2 ), 4.33 (d, 1H, J
1
0
,2
0
9.7 Hz, H-1 ), 4.19–4.08 (m, 3H, H-
3
.2. Hydroximoyl chlorides
0
0
0
13
, H-6 a, H-6 b), 1.91, 1.99, 2.05 (4 ꢂ s, 12H, 4 ꢂ COCH
SOCD 93 MHz):
), 153.8 (C-2), 145.7 (C-3a), 139.3 (C-9a), 136.6 (C-6a),
30.3 (C-5), 129.5 (C-8), 123.5 (C-9b), 121.3 (C-6), 119.3 (C-7),
3
);
C
NMR (CD
3
3
,
d
171.7, 171.1, 171.0, 170.6
The
D-gluco-,
D
-xylo-,
D-galacto-, and
D-manno-hydroximoyl
(
4 ꢂ COCH
3
chlorides 4, 11, 14 and 17 were prepared, as previously repor-
1
4,41b
1
1
3
ted,
responding pyranosylformaldoxime
until the colour changed from blue to green. On warming to room
by passing dry chlorine gas through a solution of the cor-
14,41d
0
0
15.3 (C-4), 104.0 (C-9), 78.2, 75.8, 74.1, 70.9, 69.5 (C-1 , C-2 , C-
2
in dry CH Cl
2
at ꢀ78 °C
0
0
0
0
, C-4 , C-5 ), 63.1 (C-6 ), 22.2, 22.0, 21.9, 21.8 (4 ꢂ COCH
3
); FAB-

4
8
I. A. S. Smellie et al. / Carbohydrate Research 346 (2011) 43–49
+
+
MS: m/z 499 [M+1] ; HRFABMS: Found: m/z 499.1717, C25
26
H N
2
O
9
FABMS: m/z 499 [M+1] ; HRFABMS: Found: m/z 499.1721,
C H N O
25 26 2 6
requires [M+1]+ 499.1717. Crystals suitable for X-ray diffraction
studies (vide infra) were obtained by recrystallisation of a purified
sample from EtOAc/40–60 petroleum ether.
requires [M+1] 499.1717.
+
3.3.8. 2-(2,3,4,6-Tetra-O-acetyl-b-
D
-
mannopyranosyl)perimidime (16)
2
D
0
3
.3.4. 2-(3,4,6-Tri-O-acetyl-2-deoxy-1,2-didehydro-
D-arabino-
Yellow solid (55%): mp 120–121 °C; ½
a
ꢃ
ꢀ193 (c 0.75, CHCl
3
);
1
hexopyranosyl)perimidime (9)
R
f
0.20 (Et
2
O); H NMR (CD
3
SOCD
3
, 360 MHz): d 10.06 (br s, 1H,
2
D
0
Yellow solid (34%): mp 154–155 °C; ½
aꢃ
175 (c 0.2, CHCl ); R
3
f
NH), 7.19–7.03 (m, 4H, H-5, H-6, H-7, H-8), 6.60 (m, 1H, H-4),
1
0
0
.34 (Et
2
O); H NMR (CD
3
SOCD
3
, 360 MHz): d 10.28 (br s, 1H,
6.50 (m, 1H, H-9), 5.67 (dd, 1H, J
2
0
,3
0
3.4, J
2
0
,1
0
1.1 Hz, H-2 ), 5.36
0
NH), 7.18–7.00 (m, 4H, H-5, H-6, H-7, H-8), 6.58 (m, 1H, H-4),
(dd, 1H, J
3
0
,4
0
10.1, J
3
0
,2
0
3.4 Hz, H-3 ), 5.17 (dd, 1H, J
4
0
,3
0
10.1, J
4
0
,4
0
0
0
0
6
4
1
9
1
(
(
6
.56 (m, 1H, H-9), 5.92 (d, 1H, J
2
0
,3
0
3.8 Hz, H-2 ), 5.44 (m, 1H, H-
10.0 Hz, H-4 ), 4.83 (d, 1H, J
1
0
,2
0
1.1 Hz, H-1 ), 4.34 (dd, 1H, J
6
0
b,6
0
a
0
0
0
0
), 5.22 (m, 1H, H-3 ), 4.69 (m, 1H, H-5 ), 4.59 (dd, 1H, J
6
0
b,6
0
a
12.2, J
6
0
b,5
0
5.7 Hz, H-6 b), 4.14 (dd, 1H, J
6
0
a,6
0
b
12.2, J
6
0
a,5
0
2.5 Hz, H-
);
), 153.8
0
0
0
0
2.3, J
6
0
b,5
0
5.5 Hz, H-6 b), 4.24 (m, 1H, H-6 a), 2.07, 2.06 (3 ꢂ s,
6 a), 4.09 (m, 1H, H-1 ), 2.08, 2.04, 2.00 (4 ꢂ s, 12H, 4 ꢂ COCH
3
1
3
13
H, 3 ꢂ COCH
3
); C NMR (CD
3
SOCD
3
, 93 MHz): d 171.6, 171.3,
C NMR (CD
3
SOCD
3
, 93 MHz): d 171.7, 171.2 (4 ꢂ COCH
3
0
70.7 (3 ꢂ COCH
3
), 148.6 (C-2), 148.1 (C-1 ), 145.8 (C-3a), 139.1
C-9a), 136.6 (C-6a), 130.4 (C-5), 129.5 (C-8), 123.7 (C-9b), 121.1
C-6), 119.5 (C-7), 115.3 (C-4), 104.6 (C-9), 99.1 (C-2 ), 76.1, 69.7,
(C-2), 145.6 (C-3a), 139.0 (C-9a), 136.6 (C-6a), 130.3 (C-5), 129.4
(C-8), 123.4 (C-9b), 120.8 (C-6), 119.7 (C-7), 114.8 (C-4), 104.5
0
0
0
0
0
0
(C-9), 78.0, 75.3, 72.3, 69.0, 68.4 (C-1 , C-2 , C-3 , C-4 , C-5 ), 63.1
0
0
0
0
0
9.7 (C-3 , C-4 , C-5 ), 61.6 (C-6 ), 22.2, 22.1, 21.9, 21.8 (3 ꢂ COCH
3
);
(C-6 ), 22.2, 22.0, 21.9, 21.8 (4 ꢂ COCH
3
); FABMS: m/z 499
+
+
FABMS: m/z 439 [M+1] ; HRFABMS: Found: m/z 439.1507,
[M+1] ; HRFABMS: Found: m/z 499.1713, C25
H
26
N
2
O
9
requires
+
+
C
25
H
26
N
2
O
7
requires [M+1] 439.1505.
[M+1] 499.1717.
3
.3.5. 2-(2,3,4-Tri-O-acetyl-b-
D
-xylopyranosyl)perimidime (12)
3.3.9. 2-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]perimidime (19)
20
20
Orange solid (60%): mp 169–170 °C; ½
a
ꢃ
ꢀ40 (c 0.2, CHCl
3
); R
f
Yellow solid (55%): mp 101–102 °C; ½
a
ꢃ
60 (c 0.2, CHCl
3
); R
, 360 MHz): d 10.13 (br s, 1H,
NH), 7.04–6.68 (m, 4H, H-5, H-6, H-7, H-8), 6.37 (m, 2H, H-4, H-
f
D
D
1
1
0
7
1
.27 (Et
2
O); H NMR (CD
3
SOCD
3
, 360 MHz): d 10.48 (br s, 1H, NH),
2 3 3
0.60 (Et O); H NMR (CD SOCD
.17–6.99 (m, 4H, H-5, H-6, H-7, H-8), 6.54 (m, 1H, H-4), 6.42 (m,
0
0
0
H, H-9), 5.41 (dd, 1H, J
3
0
0
,2
0
9.6, J
3
0
,4
0
9.5 Hz, H-3 ), 5.24 (dd, 1H,
9), 4.67 (dd, 1H, J
4
0
,5
0
a
6.4, J
4
0
,5
0
b
6.4 Hz, H-4 ), 4.02 (m, 2H, H-5 a,
0
0
13
J
2
0
,1
0
9.7, J
2
0
,3
0
9.6 Hz, H-2 ), 5.02 (m, 1H, H-4 ), 4.24 (d, 1H, J
1
0
,2
0
H-5 b), 1.26, 1.21 (2 ꢂ s, 6H, 2 ꢂ CH
3
);
3 3
C NMR (CD SOCD ,
0
0
9
.7 Hz, H-1 ), 4.10 (dd, 1H, J
5
0
e,5
0
a
11.0, J
5
0
e,4
0
5.5 Hz H-5 e), 3.67
93 MHz): d 155.5 (C-2), 144.3 (C-3a), 137.5 (C-9a), 134.9 (C-6a),
0
(
dd, 1H, J
5
0
e,5
0
a
11.0, J
5
0
e,4
0
10.9 Hz H-5 a), 2.05, 2.03, 1.93 (3 ꢂ s,
128.5 (C-5), 127.7 (C-8), 121.8 (C-9b), 119.0 (C-6), 117.6 (C-7),
1
3
0
0
0
9
1
H, 3 ꢂ COCH
3
); C NMR (CD
3
SOCD
3
, 93 MHz): d 171.2, 171.1,
113.4 (C-4), 109.8 (C-2 ), 104.5 (C-9), 73.9 (C-4 ), 66.6 (C-5 ),
+
70.7 (3 ꢂ COCH
3
), 154.0 (C-2), 145.8 (C-3a), 139.4 (C-9a), 136.6
25.66, 25.2 (2 ꢂ CH
3
); FABMS: m/z 268 [M+1] ; HRFABMS: Found:
+
(
C-6a), 130.3 (C-5), 129.5 (C-8), 123.6 (C-9b), 121.1 (C-6), 119.2
m/z 268.1121, C25H N O requires [M+1] 268.1212.
26 2 9
0
0
(
3
4
C-7), 115.0 (C-4), 104.1 (C-9), 78.8, 73.6, 71.2, 69.8 (C-1 , C-2 , C-
0
0
0
, C-4 ), 66.8 (C-5 ), 22.0, 21.9, 21.8 (3 ꢂ COCH
3
); FABMS: m/z
requires
3.3.10. 2-(9-Anthryl)perimidine (1, R = 9-anthryl)
solution of anthracene-9-carbonitrile oxide53 (192 mg,
+
27 [M+1] ; HRFABMS: Found: m/z 427.1510, C22
H
22
N
2
O
7
A
+
[
M+1] 427.1505.
0.88 mmol) and 1,8-diaminonaphthalene (166 mg, 1.05 mmol) in
ethanol (10 mL) was heated under reflux for 17 h. The solvent
was removed in vacuo and dichloromethane (20 mL) added. The
3
.3.6. 2-(3,4-Di-O-acetyl-2-deoxy-1,2-didehydro-
D-threo-
pentopyranosyl)perimidime (13)
resulting solution was washed three times with aq CuSO
4%) and filtered through Celite. The organic layer was washed with
aq NaHCO (30 mL), dried (MgSO ), the solvent removed in vacuo,
and the residue crystallised from ethyl acetate/hexane. Chroma-
tography (silica/0–5% diethyl Et O in hexane, gradient elution)
afforded an orange solid (90 mg, 30%); mp 194–196 °C; FABMS:
4
(20 mL,
2
D
0
Orange solid (43%): mp 148–149 °C; ½
a
ꢃ
ꢀ113 (c 0.15, CHCl
3
);
1
R
f
0.35 (Et
2
O); H NMR (CD
3
SOCD
3
, 360 MHz): d 10.49 (br s, 1H,
3
4
NH), 7.51–7.47 (m, 4H, H-5, H-6, H-7, H-8), 6.60 (m, 1H, H-4),
0
6
4
.58 (m, 1H, H-9), 6.02 (d, 1H, J
2
0
,3
0
5.1 Hz, H-2 ), 5.12 (m, 1H, H-
2
0
0
0
), 5.04 (m, 1H, H-3 ), 4.48 (m, 1H, J
5
0
b,5
0
a
12.3 Hz, H-5 b), 4.14
0
+
(
m, 1H, J
5
0
a,5
0
b
12.3 Hz, H-5 a), 2.12, 2.10 (3 ꢂ s, 9H, 3 ꢂ COCH
3
);
m/z 345 [M+1] ; HRFABMS: Found: m/z 1389, C25
H
16
N
2
requires
1
3
+
C NMR (CD
3
SOCD
3
, 93 MHz): d 171.0, 170.9 (2 ꢂ COCH
3
), 150.1
[M+1] 345.1392.
0
(
C-2), 149.2 (C-1 ), 145.9 (C-3a), 139.2 (C-9a), 136.6 (C-6a), 130.4
(
(
6
C-5), 129.5 (C-8), 123.8 (C-9b), 121.0 (C-6), 119.5 (C-7), 115.2
3.4. Crystal structure of glucopyranosyl-perimidine 8
0
0
0
0
C-4), 104.7 (C-9), 99.9 (C-2 ), 67.6, 66.2, 65.5 (C-3 , C-4 , C-5 ),
0
+
1.6 (C-6 ), 22.3, 22.2 (2 ꢂ COCH
3
); FABMS: m/z 467 [M+1] ;
Diffraction data were collected with graphite-monochromated
Cu K radiation (k = 0.71073 Å) on a Brucker SMART Apex diffrac-
+
HRFABMS: Found: m/z 367.1298, C20
H
18
N
2
O
5
requires [M+1]
a
3
67.1294.
tometer equipped with an Oxford Cryosystems low-temperature
device operating at 150 K. The structure was solved by direct meth-
2
54
3
.3.7. 2-(2,3,4,6-Tetra-O-acetyl-b-
D-galactopyranosyl)
ods and refined by full-matrix least-squares against F (SHELXS-97).
perimidime (15)
All non-H atoms were refined with anisotropic displacement param-
eters; H-atoms were placed in idealised positions. Crystal data:
2
D
0
); 1H NMR
Yellow glass (69%): ½
a
ꢃ
ꢀ120 (c 0.20, CHCl
3
(
CD
3
SOCD
3
, 360 MHz): d 10.42 (br s, 1H, NH), 7.13–7.04 (m, 4H,
C
25
H
26
N
2
O
9
ꢁH
2
O, M 498.48, yellow block, crystal dimensions
3
H-5, H-6, H-7, H-8), 6.5 (m, 2H, H-4, H-9), 5.42–5.22 (m, 3H, H-
0.50 ꢂ 0.36 ꢂ 0.20 mm , orthorhombic, space group P2
1 1 1
2 2 ,
0
0
0
0
0
2
4
1
4
1
, H-3 , H-5 ), 4.39 (m, 1H, H-4 ), 4.26 (d, 1H, J
1
0
,2
0
8.6 Hz, H-1 ),
a = 9.9570(9), b = 13.8850(12), c = 18.0620(18) Å,
a
= 90°, b = 90°,
0
3
ꢀ3
.18 (dd, 1H, J
1.5, J
ꢂ COCH
6
0
b,6
0
a
11.5, J
6
0
b,5
0
5.8 Hz, H-6 b), 4.13 (dd, 1H, J
6
0
a,6
0
b
c
= 90°, V = 2497.1(4) Å , space group P2
2
1 1
1
2 , D
c
= 1.326 mg m
,
0
0
0
7.1 Hz, H-6 a), 2.21, 2.04, 1.98, 1.95 (4 ꢂ s, 12H,
Z = 4, 16966 reflections collected, 7043 independent reflections
[R(int) = 0.0323], giving R = 0.0546 [6329 data] [F > 4 F)] and
wR = 0.1302 for all data. Complete crystallographic data for the
6
a,5
1
3
3
); C NMR (CD
3
SOCD
3
, 93 MHz): d 171.6, 171.5, 171.1,
1
r
70.2 (4 ꢂ COCH
3
), 153.6 (C-2), 145.7 (C-3a), 139.3 (C-9a), 136.6
2
(
C-6a), 130.3 (C-5), 129.4 (C-8), 123.6 (C-9b), 121.1 (C-6), 119.3
structural analysis have been deposited at the Cambridge Crystallo-
graphic Data Centre as supplementary publication number 775479.
Copies of this information can be obtained free of charge from the
0
(
2
C-7), 115.0 (C-4), 104.4 (C-9), 78.0, 75.3, 72.3, 69.0, 68.4 (C-1 , C-
, C-3 , C-4 , C-5 ), 63.2 (C-6 ), 22.2, 22.0, 21.9, 21.8 (4 ꢂ COCH
0
0
0
0
0
3
);

I. A. S. Smellie et al. / Carbohydrate Research 346 (2011) 43–49
49
Director, the Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK (fax: +44 1223 336 033, email: depos-
it@ccdc.cam.ac.uk or via www.ccdc.cam.ac.uk).
Lyakhovnenko, A. S.; Aksenov, A. V.; Borolvlev, I. V. Russ. J. Gen. Chem. 2007,
7, 1650–1651; (c) Aksenov, A. V.; Borovlev, I. V.; Aksenova, I. V.; Pisarenko, S.
V.; Kovalev, D. A. Tetrahedron Lett. 2008, 49, 707–709; (d) Aksenova, I. V.;
Lyakhovnenko, A. S.; Aksenov, A. V.; Nadein, O. N. Tetrahedron Lett. 2008, 49,
7
1808–1811; (e) Aksenova, I. V.; Aksenov, A. V.; Lyakhovnenko, A. S. Chem.
Heterocycl. Compd. Engl. Transl. 2008, 44, 765–766; (f) Aksenov, A. V.; Aksenova,
I. V.; Lobach, D. A.; Lyakhovnenko, A. S.; Lobach, D. A. Chem. Heterocycl. Compd.
Engl. Transl. 2009, 45, 66–69; (g) Aksenov, A. V.; Aksenova, I. V.; Lyakhovnenko,
A. S.; Lobach, D. A. Russ. Chem. Bull. Int. Ed. 2009, 5, 859–861; (h) Aksenov, A. V.;
Lyakhovnenko, A. S.; Andrienko, A. V.; Levina, I. I. Tetrahedron Lett. 2010, 51,
Acknowledgement
We are grateful to the EPSRC for research and maintenance
(
I.A.S.S.) grants.
2406–2408.
2
6. (a) Borovlev, I. V.; Demidov, O. P.; Pozharskii, A. F. Chem. Heterocycl. Compd.
Engl. Transl. 2002, 38, 257–258; (b) Borovlev, I. V.; Demidov, O. P.; Pozharskii, A.
F. Chem. Heterocycl. Compd. Engl. Transl. 2002, 38, 968–973; (c) Borovlev, I. V.;
Demidov, O. P.; Pozharskii, A. F. Chem. Heterocycl. Compd. Engl. Transl. 2002, 38,
References
1
2
.
.
Kiss, L.; Somsak, L. Carbohydr. Res. 1996, 291, 43–52.
1091–1095.
Chrysina, E. D.; Kosmopoulou, M. N.; Tiraidis, C.; Kardakaris, R.; Bischler, N.;
Leonidas, D. D.; Hadady, Z.; Somsak, L.; Docsa, T.; Gergely, P.; Oikonomakos, N.
G. Protein Sci. 2005, 14, 873–888.
2
2
7. Nagarajan, S.; Barthes, C.; Gourdon, A. Tetrahedron 2009, 65, 3767–3772.
8. Bazinet, P.; Yap, G. P. A.; Richeson, D. S. J. Am. Chem. Soc. 2003, 125, 13314–
13315.
3
.
(a) Benltifa, M.; Vidal, S.; Gueyrard, D.; Goekjian, P. G.; Msaddek, M.; Praly, J.-P.
Tetrahedron Lett. 2006, 47, 6143–6147; (b) Benltifa, M.; Vidal, S.; Fenet, B.;
Msaddek, M.; Goekjian, P. G.; Praly, J.-P.; Brunyanszki, A.; Docsa, T.; Gergely, P.
Eur. J. Org. Chem. 2006, 4242–4256.
2
3
9. Sachs, F. Ann. Chem. 1909, 365, 53–134.
0. Paragamian, V.; Baker, M. B.; Puma, B. M.; Reale, J. J. Heterocycl. Chem. 1968, 5,
591–597.
3
1. (a) Mobinikhaledi, A.; Foroghifar, N.; Goli, R. Phosphorus, Sulfur Silicon Relat.
Elem. 2005, 180, 2549–2554; (b) Mobinikhaledi, A.; Amrollahi, M. A.;
Foroghifar, N.; Jirandehi, H. F. Asian J. Chem. 2005, 17, 2411–2414.
2. Anisimova, V. A.; Pozharskii, A. F. Khim. Geterotsikl. Soed. 1974, 137–138.
3. Pozharskii, A. F.; Starshikov, N. M.; Pozharskii, F. T.; Mandrykin, Y. I. Khim.
Geterotsikl. Soed. 1977, 980–985.
4.
5.
6.
Farkas, I.; Szabo, I. F.; Bognar, R. Carbohydr. Res. 1977, 56, 404–406.
Mahmoud, S. H.; Somsak, L.; Farkas, I. Carbohydr. Res. 1994, 254, 91–104.
Couri, M. R.; Ludovico, I.; Santos, L.; Alves, R.; Prado, M. A.; Gil, R. F. Carbohydr.
Res. 2007, 342, 1096–1100.
3
3
7
8
.
.
Hadady, Z.; Toth, M.; Somsak, L. Arkivoc 2004, vii, 140–149.
Vojtech, M.; Petrusova, M.; Slavikova, E.; Bekesova, S.; Petrus, L. Carbohydr. Res.
3
4. Maquestiau, A.; Berte, L.; Mayence, A.; Vanden Ende, J. J. Synth. Commun. 1991,
2
006, 342, 119–123.
For reviews of benzimidazole synthesis see: (a) Preston, P. N. Chem. Rev. 1974,
4, 279–314; (b) Grimmett, M. R. Imidazole and Benzimidazole Synthesis;
Academic Press: New York, 1997; (c) Grimmett, M. R. Sci. Synth. 2002, 12, 529–
12.
2
1, 2171–2180.
9
.
3
3
5. Mobinikhaledi, A.; Foroughifar, N.; Basaki, N. Turk. J. Chem. 2009, 33, 555–560.
6. Varsha, G.; Arun, V.; Robinson, P. P.; Sebastian, M.; Varghese, D.; Leeju, P.;
Jayachandran, V. P.; Yusuff, K. K. M. Tetrahedron Lett. 2010, 51, 2174–2177.
7. Bradbury, S.; Rees, C. W.; Storr, R. C. J. Chem. Soc., Perkin Trans. 1 1972, 72–76.
8. Grundmann, C.; Kreutzberger, A. J. Am. Chem. Soc. 1955, 77, 6559–6562.
9. Trzewik, B.; Ciez, D.; Hodorowicz, M.; Stadnicka, K. Synthesis 2008, 2977–2985.
0. (a) Grundmann, C.; Grünanger, P. The Nitrile Oxides; Springer-Verlag:
Heidelberg, 1971; (b) Caramella, P.; Grünanger, P. In Padwa, A., Ed.; 1,3-
Dipolar Cycloaddition Chemistry; Wiley: New York, 1984. Chapter 3; (c)
7
6
3
3
3
4
1
0. For recent developments in benzimidazole synthesis see for example: (a)
Gogoi, P.; Konwar, D. Tetrahedron Lett. 2006, 47, 79–82; (b) Lin, S.-Y.; Isome, Y.;
Stewart, E.; Liu, J.-F.; Yohannes, D.; Yu, L. Tetrahedron Lett. 2006, 47, 2883–
2
886; (c) Wang, Y.; Sarris, K.; Sauer, D. R.; Djuric, S. W. Tetrahedron Lett. 2006,
47, 4823–4826.
11. Sasaki, T.; Yoshioka, T.; Suzuki, Y. Bull. Chem. Soc. Jpn. 1969, 42, 3335–3338.
12. Risitano, F.; Grassi, G.; Foti, F.; Caruso, F. J. Chem. Res. (S) 1983, 52.
13. Adbelhamid, A. O.; Parkanyi, C.; Rashid, S. M. K.; Lloyd, W. D. J. Heterocycl.
Chem. 1988, 25, 403–405.
0
Belen kii, L. I. In Feuer, H., Ed., 2nd ed.; Nitrile Oxides, Nitrones, and Nitronates
in Organic Synthesis; Wiley: New York, 2008. Chapter 1; (d) Paton, R. M. In
Comprehensive Organic Functional Group Transformations; Katritzky, A. R., Meth-
Cohn, O., Rees, C. W., Eds.; Pergamon: Oxford, 1995. Chapter 3.20.
1
1
1
4. Smellie, I. A. S.; Fromm, A.; Fabbiani, F.; Oswald, I. D. H.; White, F. J.; Paton, R.
M. Tetrahedron 2010, 66, 7155–7160.
5. Preliminary report: Smellie, I. A. S.; Fromm, A.; Paton, R. M. Tetrahedron Lett.
4
1. (a) Baker, K. W. J.; Gibb, A.; March, A. R.; Paton, R. M. Tetrahedron Lett. 2001, 42,
4065–4068; (b) Baker, K. W. J.; March, A. R.; Parsons, S.; Paton, R. M.; Stewart,
G. W. Tetrahedron 2002, 58, 8505–8513; (c) Baker, K. W. J.; Gibb, A.; March, A.
R.; Parsons, S.; Paton, R. M. Synth. Commun. 2003, 33, 1707–1715; (d) Baker, K.
W. J.; Horner, K. S.; Moggach, S. A.; Paton, R. M.; Smellie, I. A. S. Tetrahedron Lett.
2
009, 50, 4104–4106.
6. For reviews of perimidine chemistry see: (a) Pozharskii, A. F.; Dalnikovskaya, V.
V. Russ. Chem. Rev. 1981, 50, 816–835; (b) Liu, K. C. Zhonghua Yaoxue Zazhi
2004, 45, 8913–8916.
1
988, 40, 203–216; (c) Claramunt, R. M.; Dotor, J.; Elguero, J. Ann. Quim. 1995,
4
4
2. Llamas-Saiz, A. L.; Foces-Foces, C.; Sanz, D.; Claramunt, R. M.; Dotor, J.; Elguero,
J.; Catalan, J.; Carlos del Valle, J. J. Chem. Soc., Perkin Trans. 2 1995, 1389–1398.
3. (a) Sierra, M. A.; Manchero, M. J.; del Amo, J. C.; Fernandez, I.; Gomez-Gallego,
M.; Torres, M. R. Organometallics 2003, 22, 384–386; (b) Sierra, M. A.;
Manchero, M. J.; del Amo, J. C.; Fernandez, I.; Gomez-Gallego, M. Chem. Eur. J.
91, 151–183; (d) Undheim, K.; Benneche, C. In Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon:
Oxford, 1986; Vol. 6,. Chapter 2.
1
1
7. Woodgate, P. D.; Herbert, J. M.; Denny, W. A. Heterocycles 1987, 26, 1029–1036.
8. Alkorta, I.; Blanco, F.; Claramunt, R. M. Tetrahedron 2010, 66, 2863–2868. and
references cited therein.
2003, 9, 4943–4953.
4
4
4
4
4. Chiang, Y. H. J. Org. Chem. 1971, 36, 2146–2155.
1
9. Kobrakov, K. I.; Zubkova, N. S.; Stanevich, G. G.; Shestakova, Y. S.; Stroganov, V.
S.; Adrov, O. I. Fibre Chem. 2006, 38, 183–187.
5. Grundmann, C.; Dean, J. M. J. Org. Chem. 1965, 30, 2809–2812.
6. Jones, R. H.; Robinson, G. C.; Thomas, E. J. Tetrahedron 1984, 40, 177–184.
7. Claramunt, R. M.; Dotor, J.; Sanz, C.; Foces-Foces, C.; Llamas-Saiz, A. L.; Elguero,
J.; Flammang, R.; Morizur, J. P.; Chapon, E.; Tortajada, J. Helv. Chim. Acta 1994,
2
2
0. Goswami, S.; Sen, D.; Das, N. K. Org. Lett. 2010, 12, 856–859.
1. Herbert, J. M.; Woodgate, P. D.; Denny, W. A. J. Med. Chem. 1987, 30, 2081–
2
086.
7
7, 121–139.
8. Woodgate, P. D.; Herbert, J. M.; Denny, W. A. Magn. Reson. Chem. 1988, 26, 191–
96.
9. Yavari, I.; Adib, M.; Jahani-Moghaddam, F.; Bijanzadeh, H. R. Tetrahedron 2002,
8, 6901–6906.
2
2. (a) Morita, Y.; Aoki, T.; Fukui, K.; Nakazawa, S.; Tamaki, K.; Suzuki, S.; Fuyuhiro,
A.; Yamamoto, K.; Sato, K.; Shiomi, D.; Naito, A.; Takui, T.; Nakasuji, K. Angew.
Chem., Int. Ed. 2002, 41, 1793–1796; (b) Morita, Y.; Suzuki, S.; Fukui, K.;
Nakazawa, S.; Kitagawa, H.; Kishida, H.; Okamoto, H.; Naito, A.; Sekine, A.;
Ohashi, Y.; Shiro, M.; Sasaki, K.; Shiomi, D.; Sato, K.; Takui, T.; Nakasuji, K. Nat.
Mater. 2008, 7, 48–51.
4
4
5
1
5
0. Grimmet, M. R. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees,
C. W., Eds.; Pergamon: Oxford, 1984. Chapter 4.06 and references cited therein.
1. Cruickshank, D. W. J. Acta Crystallogr. 1957, 10, 504–508.
2. Brock, C. P.; Dunitz, J. D. Acta Crystallogr., Sect. B 1982, 38, 2218–2228.
3. Cremer, D.; Pople, J. A. J. Am. Chem. Soc. 1975, 97, 1354–1358.
4. Sheldrick, G. M. Acta Crystallogr., Sect. A 2008, 64, 112–122.
2
3. Quast, H.; Nudling, W.; Klemm, G.; Kirschfeld, A.; Neuhaus, P.; Sander, W.;
Hrovat, D. A.; Borden, W. T. J. Org. Chem. 2008, 73, 4956–4961.
5
5
5
5
2
2
4. Bowden, K.; Brownhill, A. J. Chem. Soc., Perkin Trans. 2 1997, 219–222.
5. See for example: (a) Borovlev, I. V.; Aksenov, A. V.; Aksenova, I. V.; Pisarenko, S.
V. Russ. Chem. Bull. Int. Ed. 2007, 56, 2354–2355; (b) Aksenova, I. V.;