Synthesis of novel macrocyclic crown ethers from D-glucose

Article abstract of DOI:10.1080/07328303.2016.1206115

A simple and efficient synthetic protocol for an easy access of carbohydrate-linked crown ethers from cheap and readily available D-glucose in good yields has been devised. The base-mediated cyclization of sugar-linked bis-iodo podands in CH₃CN

Full text of DOI:10.1080/07328303.2016.1206115

Journal of Carbohydrate Chemistry
ISSN: 0732-8303 (Print) 1532-2327 (Online) Journal homepage: http://www.tandfonline.com/loi/lcar20
Synthesis of novel macrocyclic crown ethers from
D-glucose
Amrita Mishra, Nidhi Mishra & Vinod K. Tiwari
To cite this article: Amrita Mishra, Nidhi Mishra & Vinod K. Tiwari (2016): Synthesis of
novel macrocyclic crown ethers from D-glucose, Journal of Carbohydrate Chemistry, DOI:
10.1080/07328303.2016.1206115
To link to this article: http://dx.doi.org/10.1080/07328303.2016.1206115
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Date: 20 August 2016, At: 10:15

JOURNAL OF CARBOHYDRATE CHEMISTRY
, VOL. , NO. , –
http://dx.doi.org/./..
Synthesis of novel macrocyclic crown ethers from D-glucose
Amrita Mishra, Nidhi Mishra, and Vinod K. Tiwari
Department of Chemistry, Centre of Advanced Study, Institute of Science, Banaras Hindu University,
Varanasi, India
ABSTARCT
ARTICLE HISTORY
Received  April 
Accepted  June 
A simple and efficient synthetic protocol for an easy access
of carbohydrate-linked crown ethers from cheap and readily
available D-glucose in good yields has been devised. The
base-mediated cyclization of sugar-linked bis-iodo podands in
CH3CN with amines, including ethylamine and furfurylamine
afforded the novel chiral monoaza-15-crown-5-type macrocyclic
crown ethers anellated to 3-O-benzyl-1,2-O-isopropylidene-
α-D-glucofuranose and 3-O-benzyl-1,2-O-isopropylidene-α-
D-allofuranose. The glucose-based crown ethers have been
characterized by spectroscopy techniques including IR, 1H NMR,
and 13C NMR.
KEYWORDS
Crown ether; Carbohydrate;
Chiral monoaza--crown-;
D-glucose; Macrocycle
GRAPHICAL ABSTRACT
Introduction
Crown ether macrocycles, specifically cryptands, are known to form complexes with
various cations, offering new possibilities in various disciplines of chemistry such as
phase-transfer catalysis, mediation of transport processes, ion chromatography, and
electroanalytical chemistry.[1,2] Carbohydrate-derived macrocycles not only allow
the possession of multifunctionality through linkage at different positions of sugar
ring, but also afford modulation of various physicochemical properties like solubil-
ity, hydrophilic/lipophilic balance, biodisponibility, etc.[3,4]
Crown ethers possessing a carbohydrate moiety form a special group of
optically active macrocycles.[5–8] The furanoid and pyranoid cyclic skeletons of
CONTACT Vinod K. Tiwari
tiwari_chem@yahoo.co.in.
Institute of Science, Banaras Hindu University, Varanasi-, India.
Department of Chemistry, Centre of Advanced Study,
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lcar.
©  Taylor & Francis Group, LLC

2
A. MISHRA ET AL.
sugars impose geometric constraints which assists the design of conformation-
ally restricted molecular platforms. Additionally, the chiral pool of carbohydrate
moiety allows the development of chiral cavities which can be beneficial for
asymmetric catalysis and chiral recognition.[9–13] The easy availability of enan-
tiomerically pure forms of sugars with known chiroptical properties readily
provide secondary binding sites for catalytic activity. Thus, synthesis of crown
ethers, containing a sugar unit in the macrocyclic ring, provide an easy way to
afford macrocycles of different chirality. The extraordinary merits associated with
sugar-based crown ethers encouraged us to explore the synthesis of two novel
monoaza-15-crown-5-type macrocyclic crown ethers anellated to 3-O-benzyl-1,2-
O-isopropylidene-α-D-glucofuranose and 3-O-benzyl-1,2-O-isopropylidene-α-D-
allofuranose, which has been described in present manuscript.
Result and discussion
Our strategy for the synthesis of sugar-linked crown ethers began with 1,2,5,
6-di-O-isopropylidene-α-D-glucofuranose 1, which can be easily obtained on ace-
tonide protection of cheap and readily available D-glucose (Sch. 1).[14] The clas-
sical diacetonide glucose 1 on 3-O-benzyl protection using benzyl bromide and
NaH as base in THF followed by selective deprotection of 5,6-isopropylidene group
under standard reaction condition affords high yield of desired glycosyl diol 4.
Introduction of a bis-chloro podand to the glycosyl cis-diol 4 offers the essen-
tial scaffold for the synthesis of target sugar-linked crown ethers. The vicinal
hydroxyl groups of compound 4 were alkylated with bis(2-chloroethyl)ether. The
compound 4 in presence of tetrabutylammonium hydrogen sulfate catalyst and
50% aqueous NaOH in a liquid–liquid two-phase system by the Gross method[7]
gave the bis-chloro derivative, i.e., 5,6-bis-O-[(2-chloroethoxy)ethyl]-3-O-benzyl-
1,2-O-isopropylidene-α-D-glucofuranose 5 as an intermediate which was purified
by flash column chromatography. Then, after the exchange of chlorine to iodine in
compound 5, accomplished by reacting it with NaI in boiling acetone leads high
yield of corresponding bis-iodo derivative, 5,6-bis-O-[(2-iodoethoxy)ethyl]-3-O-
benzyl-1,2-O-isopropylidene-α-D-glucofuranose 6. The compound 6 was obtained
in the pure form, by filtering it on celite bed then washing with acetone. The
obtained residual oil was partitioned between CH2Cl2 and water, dried over anhy-
drous Na2SO4 and the solvent was evaporated to give compound 6 in almost pure
form.
The synthesis of sugar-linked crown ether was accomplished by further sub-
jecting the bis-iodo derivative, 5,6-bis-O-[(2-iodoethoxy)ethyl]-3-O-benzyl-1,2-O-
isopropylidene-α-D-glucofuranose 6, to cyclization with primary amines. While,
attempting optimization of the reaction conditions for the synthesis of aza-crown
ethers, the effect of diverse bases was investigated for the cyclization step by
refluxing the sugar-based bis-iodo podand 6 in anhydrous acetonitrile with 2-
phenylethylamine and different inorganic and organic bases. The obtained results
revealed that in the case of inorganic bases same equivalent of either bicarbonate

JOURNAL OF CARBOHYDRATE CHEMISTRY
3
Scheme . Synthesis of D-glucose-based crown ether 7.
or carbonate bases afforded good yields of product; as was evident from the Table 1
(entry 4–6). The reaction when performed in presence of strong inorganic bases, i.e.,
NaH, LiH, and Li2CO3 the best yields of product was obtained (entry 1–3, Table 1).
In the case of amine bases, very low overall yield of aza-crown ether was obtained
(entry 7–13, Table 1). Among all used bases, Li2CO3 proved to be the most appropri-
ate base for the synthesis of aza-crown ether via the cyclization of bis-iodo podands
with primary amines.
Next, the above reaction was screened for a variety of organic solvents (Table 2).
The results clearly illustrated that the reaction proceeded best in acetonitrile sol-
vent under argon atmosphere at 60°C (refluxing conditions) and the product was
Table . Base optimization for the synthesis of aza-crown ether 7 by the reaction of bis-iodo podand
6 and -phenylethylamine in dry CHCN.
Entry
Base
LiH
LiCO
NaH
NaCO
KCO
NaHCO
KHCO
DMAP
DIPEA
DBU
Timea
Yield (%)b







































DABCO
EtN
Pyridine
aReaction time in hours. bIsolated yield of product 7.

4
A. MISHRA ET AL.
Table . Solvent optimization for the synthesis of aza-crown ethers by the reaction of compound 6
and -phenylethylamine in presence of LiCO base at refluxing conditions of various solvents.
Entry
Solvent
Timea
Yield (%)b











Acetone




















Methanol
Acetonitrile
THF
,-Dioxane
EtOAc
EtO
Chloroform
Dichloromethane
Benzene
Toluene
ND
Ta
aReaction time in hours. bIsolated yield of product 7. ND stands for “product not detected”and “ta”stands for “trace
amount”.
isolated in good yield (entry 3, Table 2). In case of non-polar solvents, such as ben-
zene and toluene the product was obtained only in trace amount or not detected
at all under refluxing conditions, even after stirring the reaction for longer dura-
tions (60 h) (entry 10–11, Table 2). The reaction also showed poor performance
in methanol, tetrahydrofuran, acetone, 1,4-dioxane, diethyl ether, acetonitrile, ethyl
acetate, dichloromethane, and chloroform in terms of yield and reaction time. In all
these cases, the product yield did not improve on subjecting the reaction for long-
duration stirring under refluxing conditions.
Therefore, under the above optimized reaction conditions, the bis-iodo
podand 5,6-bis-O-[(2-iodoethoxy)ethyl]-3-O-benzyl-1,2-O-isopropylidene-α-D-
glucofuranose 6 was refluxed for 40 h with primary amine (2-phenylethylamine) in
presence of dry Li2CO3 as base and acetonitrile as solvent under argon atmosphere
at 60°C (refluxing conditions) to afford an oily aza-crown ether, compound 7.
The crude product was then subjected to work-up and purification by column
chromatography (twice: on Al2O3 then on silica gel using 2–5% MeOH in CHCl3
as eluent) to afford 3-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose-based
crown ether 7 in 60% yield (Sch. 1). The structure of compound 7 was justified
based on its spectroscopic characterization. The formation of aza-crown ether 7
from its corresponding bis-iodo podand 6 was confirmed by the appearance of
additional signals of aromatic protons in the 1H NMR spectra operated at 300 MHz.
The multiplet appearing in the range of δ 7.31–7.16 was integrated to 10 proton res-
onances indicating the presence of 10 aromatic protons which implied the presence
of two phenyl rings, one linked to the amine side chain of the aza-crown ether and
the other phenyl ring is of the benzyl group which is used for protecting the free
hydroxyl group at C-3 carbon of glucofuranose ring. The signal corresponding to
the anomeric proton (H1) of the glucofuranose ring appeared as a doublet at δ 5.88
(J = 3.6 Hz). A signal integrated to one proton at δ 4.67 (J = 11.7 Hz) appearing
as a doublet was established for the benzylic proton –OCHAPh. Two doublets
integrated to one proton each appeared at δ 4.58 (J = 3.9 Hz) and 4.51 (J = 11.4 Hz)
correspond to the proton present at C-2 of furanose ring (H2) and for the second

JOURNAL OF CARBOHYDRATE CHEMISTRY
5

Figure . H NMR spectrum of compound 7.
benzylic proton –OCHBPh. The protons at the C-4 and C-3 of sugar backbone
(H4 and H3) appeared as doublet at δ 4.16 (J = 9.3 Hz) and 4.08 (J = 2.7 Hz). The
23 protons of the crown ethers including the protons of the –O–CH2–CH2–O–
unit as well as the four ethylene protons linked to the nitrogen side chain of the
aza-crown ring appeared as multiplets in the range of δ 3.98–3.47. Two singlets
integrated to three protons each appeared at δ 1.47 and 1.30 correspond to two
methyl resonances of isopropylidene unit (Fig. 1).
In the IR spectra of compound 7 the formation of aza-crown ring was evidenced
by the appearance of absorption bands corresponding to C–N (1217 cm−1) and C–
O–C stretch (1076 cm−1), respectively. The 13C NMR spectra of compound 7 cor-
respond to 32 carbon resonances. In the 13C NMR, the signals at δ 140.4, 137.4,
128.7 (2C), 128.4 (2C), 128.2 (2C), 127.8 (2C), 127.6, 125.8 ppm were attributed for
the carbon of phenyl ring. The appearance of peaks of 12 aromatic carbons clearly
evidenced the presence of two phenyl rings; one situated at the side arm of nitro-
gen atom of crown ring and the other of the benzyl group which is used for the
3-O-hydroxyl protection at the C-3 carbon of glucofuranose ring. The characteris-
tic signal of the anomeric carbon of glucofuranose ring appeared at δ 105.1 which
lent further support to the assigned structure of desired D-glucose-based aza-crown
ether (Fig. 2). A molecular ion peak at m/z 571 [M+H]+ in mass spectrum finally
confirmed the structure of compound 7. The synthesized compound 7 also showed
good specific rotation [α]25D = −34.96 (c 0.4, chloroform).
Following the similar protocol, bis-iodo podand of another sugar, i.e., D-allose
has been prepared (Sch. 2). For this purpose, 1,2:5,6-di-O-isopropylidene-α-D-
allofuranose 2 was obtained from 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose
1 using one-pot Swern oxidation-reduction protocol known in literature.[15,16]

6
A. MISHRA ET AL.
Figure . C NMR spectrum of compound 7.
The method oxidizes the secondary alcohol to corresponding ketone, 1,2:5,6-
di-O-isopropylidene-α-D-ribo-hexofuranos-3-ulose, followed by subsequent in
situ sodium borohydride reduction at low temperature (−78°C) which inverts
the configuration at 3-position of glucofuranose sugar to afford 1,2:5,6-di-O-
isopropylidene-α-D-allofuranose 2 in 89% yield obtained after purification by flash
column chromatography. Structure of compound 2 was in accordance with the pre-
vious report, where NMR (1H and 13C) and MS data were closely matched to the
known compound.[15]
The vicinal hydroxyl groups of the cis diol of D-allose sugar 9 were alky-
lated with bis(2-chloroethyl)ether in the presence of phase transfer catalyst as
described earlier to afford intermediate; 5,6-bis-O-[(2-chloroethoxy)ethyl]-3-O-
benzyl-1,2-O-isopropylidene-α-D-allofuranose 10. The exchange of chlorine to
iodine in intermediate 8 was accomplished by the reaction of bis-chloro deriva-
tive of D-allose with NaI in boiling acetone to afford bis-iodo derivative; 5,6-bis-
O-[(2-iodoethoxy)ethyl]-3-O-benzyl-1,2-O-isopropylidene-α-D-allofuranose11.
Similarly, for the synthesis of D-allose-based crown ether, the synthesized bis-iodo
derivative; 5,6-bis-O-[(2-iodoethoxy)ethyl]-3-O-benzyl-1,2-O-isopropylidene-α-
D-allofuranose 11 was reacted with furfurylamine and dry lithium carbonate in
refluxing acetonitrile for 46 h under similar conditions as for the synthesis of
D-glucose-based crown ether, to afford aza-crown ether 12. The crude product was
subjected to work-up and purification by chromatography (twice: on Al2O3 then
on silica gel using 2–5% MeOH in CHCl3 as eluent) to afford 3-O-benzyl-1,2-O-
isopropylidene-α-D-allofuranose-based crown ether 12 in 55% yield (Sch. 2).>
The synthesized compound 12 also showed good specific rotation [α]27D = −37.95
(c 0.2, chloroform).

JOURNAL OF CARBOHYDRATE CHEMISTRY
7
Scheme . Synthesis of D-allose-based crown ether 12.
Conclusions
Conclusively, we have developed two novel chiral monoaza-15-crown-5 type
macrocyclic crown ethers anellated to 3-O-benzyl-1,2-O-isopropylidene-α-D-
glucofuranose and 3-O-benzyl-1,2-O-isopropylidene-α-D-allofuranose. The
developed D-glucose and D-allose-based lariat ethers might have application
for induction of stereoselectivity in certain reactions, which is under progress in
our lab. Additionally these synthesized lariat ethers might also possess enantiomeric
discrimination ability toward chiral ammonium salts.[4] The work-up procedure
involved in the synthesis of these crown ethers is simple and the obtained product is
in good yield with less or no by-product formation. The bis-iodo podands involved
in the cyclization step of the synthesis of mono-aza crown ethers displayed good
compatibility with different tertiary amines. The facile accessibility to the starting
materials is very interesting and an appealing aspect. Therefore, a simple and read-
ily adaptable approach has been devised for an easy access to carbohydrate-based
crown ethers in appreciable yields.
Supporting information
Copies of 1H and 13C NMR spectra for all the new compounds are given. This mate-
rial is available free of charge via the Internet.

8
A. MISHRA ET AL.
Experimental
General Remarks: All the reactions were carried out in anhydrous solvents under
an argon atmosphere in one hour oven dried glassware at 100°C. Solvents were
purified by standard procedures. Yields refer to chromatographically pure mate-
rial. All reagents and solvents were of pure analytical grade. Thin layer chromatog-
raphy (TLC) was performed on 60 F254 silica gel, pre-coated on aluminum plates
and revealed with either a UV lamp (λ
= 254 nm) or a specific color reagent
max
(Draggendorff reagent or iodine vapors) or by spraying with methanolic-H2SO4
solution and subsequent charring by heating at 100°C. H and 13C NMR were
1
recorded at 300 and 75 MHz, respectively. Chemical shifts given in ppm downfield
from internal TMS; J values in Hz. Mass spectra recorded using electrospray ioniza-
tion mass spectrometry (ESI-MS). Infrared spectra recorded as Nujol mulls in KBr
plates. Elemental analysis was performed using a C, H, N analyzer and results were
found to be within 0.4% of the calculated values.
Procedure for the synthesis of orthogonally protected sugars: The protected sug-
ars were prepared from readily available carbohydrate (D-glucose) using standard
protection methodologies.[14]
Procedure for the synthesis of 1,2:5,6-Di-O-isopropylidene-α-D-allofuranose
(8): The compound 8 can be readily prepared from 1,2:5,6-di-O-isopropylidene-α-
D-glucofuranose 1 by following the procedure of an adapted Swern oxidation-
sodium borohydride reduction under one-pot conditions as reported in
literature.[15]
5,6-Bis-O-[(2-chloroethoxy)ethyl]-3-O-benzyl-1,2-O-isopropylidene-α-D-glu-
cofuranose (5): To
a mixture of 3-O-benzyl-1,2-O-isopropylidene-α-D-
glucofuranose compound 3 (8.0 g, 25.8 mmol) and Bu4NHSO4 (6.53 g, 19.2
mmol) in bis(2-chloroethyl) ether (44.0 mL, 0.38 mmol) was vigorously stirred
with 50% aqueous NaOH solution (52.0 mL, 0.83 mmol) for 12 h at rt. After
completion of reaction (monitored by TLC), the reaction mixture was poured
on a mixture of water (80 mL) and CH2Cl2 (80 mL) and extracted with CH2Cl2
thrice. The combined organic phases were dried over Na2SO4. After the removal of
solvent in vaccum, bis-(2-chloroethyl)ether was removed by another distillation in
vacuum. The crude product was purified by flash column chromatography (SiO2)
using gradient mixtures of methanol in CHCl3 as eluant to afford compound 5 in
65% yield. Pale yellow liquid (8.77 g, yield 65%); Rf = 0.67 (60% ethyl acetate/n-
1
hexane); H NMR (300 MHz, CDCl3): δ 7.24 (m, 5H), 5.78 (d, J = 3.6 Hz, 1H),
4.55 (d, J = 5.1 Hz, 2H), 4.50 (m, 1H), 4.08 (d, J = 9.3 Hz, 1H), 4.01 (m, 1H), 3.78
(d, J = 11.4 Hz, 2H), 3.62 (d, J = 6 Hz, 5H), 3.56 (m, 8H), 3.49 (d, J = 6.3 Hz, 4H),
1.37 (s, 3H), 1.21 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ 137.5, 128.1 (2C),
127.5, 127.4 (2C), 111.4, 104.9, 81.6, 81.5, 78.6, 75.6, 71.9, 71.7, 71.0, 70.9, 70.6,
70.5, 70.3, 69.8, 42.6 (2C), 26.5, 26.0 ppm; IR (KBr) νmax: 2932, 2871, 1497, 1455,
1356, 1374, 1256, 1110, 1075 (C–O–C), 1026, 887, 858 (C–Cl), 744, 700, 665 cm−1;
MS: m/z 524 [M+H]+; Anal. Calcd. for C24H36Cl2O8: C, 55.07; H, 6.93; Found: C,
55.01; H, 6.98.

JOURNAL OF CARBOHYDRATE CHEMISTRY
9
5,6-Bis-O-[(2-iodoethoxy)ethyl]-3-O-benzyl-1,2-O-isopropylidene-α-D-gluco-
furanose (6): To a stirred solution of 5,6-bis-O-[(2-chloroethoxy)ethyl]-3-O-
benzyl-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose 5 (8.0 g, 15.2 mmol)
in dry acetone was added dry NaI (6.82 g, 45.5 mmol) and Na2CO3 (0.104 g,
0.98 mmol) and the reaction was refluxed with stirring for 30 h. Then, the
reaction was cooled to rt and filtered on celite bed and washed twice with
acetone. The combined organic phases were evaporated. The obtained resid-
ual oil was dissolved in CH2Cl2 (60 mL) and washed with water thrice, dried
over Na2SO4 and evaporated. The product compound 6 was now obtained in
the pure form after this work-up procedure. Yellow oil (9.17 g, yield 85%); Rf
1
= 0.62 (60% ethyl acetate/n-hexane); H NMR (300 MHz, CDCl3): 7.33 (m,
5H), 5.87 (d, J = 3.3 Hz, 1H), 4.69 (m, 1H), 4.64 (d, J = 5.4 Hz, 1H), 4.58
(d, J = 3.6 Hz, 1H), 4.16 (d, J = 9.6 Hz, 1H), 4.10 (m, 1H), 3.87 (d, J = 9.9 Hz, 2H),
3.76-3.69 (m, 4H), 3.65 (m, 5H), 3.61 (d, J = 6.3 Hz, 4H), 3.57 (d, J = 2H), 3.22 (dd,
J = 7.2, 15 Hz, 2H), 1.47 (s, 3H), 1.30 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ
137.6, 128.3 (2C), 127.7, 127.6 (2C), 111.6, 105.1, 81.8, 81.7, 78.8, 75.8, 72.3, 72.2,
71.9, 71.7, 71.2, 71.1, 70.8, 70.1, 26.7, 26.2, 3.0, 2.9 ppm; IR (KBr) νmax: 2934, 2872,
1497, 1459, 1354, 1378, 1258, 1109, 1076 (C–O–C), 1025, 889, 858, 665, 550 (C–I),
553 cm−1; MS: m/z 707 [M+H]+; Anal. Calcd. for C24H36I2O8: C, 40.81; H, 5.14;
Found: C, 40.91; H, 5.11.
3-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranose-based crown ether (7): To
a stirred solution of lithium carbonate (0.09 g, 1.05 mmol) in anhydrous ace-
tonitrile (80 mL) was added a solution of 2-phenyl ethylamine (0.815 mL, 6.45
mmol) and 5,6-bis-O-[(2-iodoethoxy)ethyl]-3-O-benzyl-1,2-O-isopropylidene-α-
D-glucofuranose 6 (5.0 g, 7.08 mmol). The resulting reaction mixture was refluxed
for 40 h with stirring under argon atmosphere. After this, the reaction mixture was
allowed to cool to rt and the precipitate was filtered off. The precipitate was washed
thrice with acetonitrile. Thus, obtained combined organic phases were evaporated
and the residual oil was dissolved in CHCl3 (60 mL) and washed with water (2 ×
40 mL). Hence, obtained organic layer was dried over Na2SO4 and concentrated
in vacuo. The obtained oily crude product was purified by chromatography (twice:
on Al2O3 then on silica gel using 2–5% MeOH in CHCl3 as eluent) to afford pure
compound 7. Yellow liquid (9.17 g, yield 60%); Rf = 0.42 (5% methanol/ CHCl3);
[α]25D = −34.96 (c 0.4, CHCl3); 1H NMR (300 MHz, CDCl3): δ 7.31–7.23 (m, 8H),
7.18–7.16 (m, 2H), 5.88 (d, J = 3.6 Hz, 1H), 4.67 (d, J = 11.7 Hz, 1H), 4.58 (d, J =
3.9 Hz, 1H), 4.51 (d, J = 11.4 Hz, 1H), 4.16 (d, J = 9.3 Hz, 1H), 4.08 (d, J = 2.7 Hz,
1H), 3.97 (d, J = 8.4 Hz, 1H), 3.89–3.82 (m, 2H), 3.62–3.55 (m, 10H), 3.49–3.47
(m, 2H), 2.89–2.76 (m, 8H), 1.47 (s, 3H), 1.30 (s, 3H) ppm; 13C NMR (75 MHz,
CDCl3): δ 140.4, 137.4, 128.7 (2C), 128.4 (2C), 128.2 (2C), 127.8 (2C), 127.6, 125.8,
111.7, 105.1, 81.6, 81.5, 79.1, 75.4, 72.3, 71.8, 71.1, 70.29, 70.25, 70.1, 70.0, 69.4, 59.2,
54.8, 54.3, 33.8, 26.7, 26.2 ppm; IR (KBr) νmax: 2925, 2855, 1641, 1497, 1455, 1374,
1258, 1217 (C–N stretch), 1109, 1076 (C–O–C), 1027, 887, 746, 700 cm−1; MS: m/z
571 [M+H]+; Anal. Calcd. for C32H45NO8: C, 67.23; H, 7.93; N, 2.45; Found: C,
67.15; H, 7.82; N, 2.41.

10
A. MISHRA ET AL.
5,6-Bis-O-[(2-chloroethoxy)ethyl]-3-O-benzyl-1,2-O-isopropylidene-α-D-
allofuranose (10): To a mixture of 3-O-benzyl-5,6-O-isopropylidene-α-D-
allofuranose compound 2 (4.0 g, 12.9 mmol) and Bu4NHSO4 (3.26 g, 9.62 mmol)
in bis(2-chloroethyl) ether (22.0 mL, 0.19 mmol) was vigorously stirred with 50%
aqueous NaOH solution (24.0 mL, 0.41 mmol) for 12 h at rt. After completion
of reaction (monitored by TLC), the reaction mixture was poured on a mixture
of water (70 mL) and CH2Cl2 (70 mL) and extracted with CH2Cl2 thrice. The
combined organic phases were dried over Na2SO4. After the removal of solvent in
vaccum, bis(2-chloroethyl)ether was removed by another distillation in vaccum.
The crude product was purified by flash column chromatography (SiO2) using
gradient mixtures of methanol in CHCl3 as eluant to afford compound 10 in 56%
yield. Pale yellow liquid (4.38 g, yield 56%); Rf = 0.62 (65% ethyl acetate/n-hexane);
1H NMR (300 MHz, CDCl3): δ 7.32–7.26 (m, 5H), 5.87 (d, J = 3.6 Hz, 1H), 4.64
(d, J = 5.1 Hz, 2H), 4.57 (d, J = 3.6 Hz, 1H), 4.17 (dd, J = 2.7, 9.3 Hz, 1H), 4.10 (d,
J = 2.4 Hz, 1H), 3.93–3.87 (m, 1H), 3.84 (d, J = 7.2 Hz, 1H), 3.75–3.72 (m, 5H),
3.68–3.53 (m, 12H), 1.47 (s, 3H), 1.30 (s, 3H) ppm; 13C NMR (75 MHz, CDCl3): δ
137.7, 128.3 (2C), 127.7, 127.5 (2C), 111.6, 105.1, 81.8, 81.6, 78.8, 75.8, 72.2, 71.9,
71.2, 71.1, 70.8, 70.7, 70.4, 70.0, 42.7 (2C), 26.7, 26.2 ppm; IR (KBr) νmax: 2925,
2869, 1674, 1498, 1455, 1356, 1374, 1255, 1164, 1075 (C–O–C), 1025, 885, 857
(C–Cl), 742, 700, 663 cm−1; MS: m/z 524 [M+H]+; Anal. Calcd. for C24H36Cl2O8:
C, 55.04; H, 6.93; Found: C, 55.13; H, 7.00.
3-O-benzyl-1,2-O-isopropylidene-α-D-allofuranose-based crown ether (12): To
a stirred solution of dry lithium carbonate (0.07 g, 4.24 mmol) in anhy-
drous acetonitrile (80 mL) was added a solution of furfurylamine (0.40 mL,
4.63 mmol), 5,6-bis-O-[(2-iodoethoxy)ethyl]-3-O-benzyl-1,2-O-isopropylidene-α-
D-allofuranose 11 (3.0 g, 4.24 mmol). The resulting reaction mixture was refluxed
for 46 ho with stirring under argon atmosphere. After this, the reaction mixture was
allowed to cool to rt and the precipitate was filtered off. The precipitate was washed
thrice with acetonitrile. Thus, obtained combined organic phases were evaporated
and the residual oil was dissolved in CHCl3 (60 mL) and washed with water (2 ×
40 mL). Hence, obtained organic layer was dried over Na2SO4 and concentrated
in vacuo. The obtained oily crude product was purified by chromatography (twice:
on Al2O3 then on silica gel using 2–5% MeOH in CHCl3 as eluent) to afford pure
compound 12. Yellow liquid (1.27 g, yield 55%); Rf = 0.45 (6% methanol/ CHCl3);
[α]25D = −37.95 (c 0.2, CHCl3); 1H NMR (300 MHz, CDCl3): δ 7.32–7.26 (m, 6H),
6.29 (d, J = 11.7 Hz, 1H), 6.16 (m, 1H), 5.87 (s, 1H), 4.64 (d, J = 3.3 Hz, 1H), 4.60 (d,
J = 6 Hz, 1H), 4.56 (m, 1H), 4.46 (d, J = 5.7 Hz, 1H), 4.16 (m, 1H), 4.08 (m, 1H), 3.87
(d, J = 10.2 Hz, 2H), 3.72 (d, J = 5.7 Hz, 4H), 3.64–3.61 (m, 4H), 3.58 (d, J = 7.5 Hz,
4H), 3.52–3.49 (m, 4H), 2.69 (d, J = 6 Hz, 2H), 1.46 (s, 3H), 1.29 (s, 3H) ppm; 13
C
NMR (75 MHz, CDCl3): δ 141.7, 137.7, 128.3 (3C), 127.7, 127.5 (2C), 111.6, 109.9,
105.0, 81.8, 81.6, 78.8, 75.7, 72.4, 71.9, 71.2, 71.0, 70.8, 70.7, 70.4, 70.2, 69.9, 69.6,
53.4, 51.1, 26.7, 26.2 ppm; IR (KBr) νmax: 2934, 2870, 1633, 1497, 1455, 1374, 1298,
1254 (C–N stretch), 1110, 1075 (C–O–C), 1026, 887, 743, 699, 655 cm−1; MS: m/z

JOURNAL OF CARBOHYDRATE CHEMISTRY
11
548 [M+H]+; Anal. Calcd. for C29H41NO9: C, 63.60; H, 7.55; N, 2.56; Found: C,
63.45; H, 7.49; N, 2.59.
Funding
Authors gratefully acknowledge Council of Scientific & Industrial Research (CSIR), New Delhi
(Grant No. 02(0173)/13/EMR-II) for the funding and CISC, Department of Chemistry, Banaras
Hindu University for providing spectroscopic data of synthesized compounds and Prof. Ashok
Prasad for his help during the preparation of manuscript.
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