Facile synthesis of 5-hydroxymethylfurfural: A sustainable raw material for the synthesis of key intermediates toward 21,23-dioxaporphyrins

Article abstract of DOI:10.1039/c5ra19400h

In a simple and conceptually designed method for the dehydration of fructose on a solid support, 5-hydroxymethylfurfural (HMF) was synthesized in more than 95% isolated yield from fructose under very mild conditions at room temperature. The loading of fructose on the solid support reduced the intermolecular interactions between fructose/intermediates, diminished the formation of polymeric material (humin) and increased the selectivity towards HMF formation. The synthesized HMF was readily converted into key intermediates toward the simpler synthesis of 21,23-dioxaporphyrins.

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Facile synthesis of 5-hydroxymethylfurfural: A sustainable raw
material for synthesis of key intermediates toward 21,23-
dioxaporphyrins
Received 00th January 20xx,
Accepted 00th January 20xx
Rajamani Rajmohan, Subramaniyan Gayathri and Pothiappan Vairaprakash*
DOI: 10.1039/x0xx00000x
In a simple and conceptually designed method for dehydration of fructose on a solid support, 5-hydroxymethylfurfural
(HMF) was synthesized in more than 95% isolated yields from fructose under very mild conditions at room temperature.
Loading of fructose on solid support reduced intermolecular interaction between fructose/intermediates, diminished the
formation polymeric material (Humin) and increased the selectivity towards HMF formation. The synthesized HMF was
readily converted into key intermediates toward the simpler synthesis of 21,23-dioxaporphyrins.
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be broadly categorized as (i) aqueous,23-25 (ii) organic,26-34 (iii)
biphasic35-40 and (iv) ionic liquid.41-45 The main drawback of
using aqueous/biphasic system is rehydration. In the presence
Introduction
Depletion of fossil fuels, its impact on the ecology and
increasing demand for raw materials necessitate the smooth
transition from fossil fuel era to sustainable era. In this
context, various plant derived organic matters have been
proposed as energy alternate and sustainable raw materials.1-8
Among the plant derived matters, 2,5-dimethylfurfural (DMF)
best fits by its energy content to meet with present locomotive
system,9 and DMF was obtained from 5-hydroxymethylfurfural
(HMF).10-13 HMF derived 2,5-furandicarboxylic acid is
considered as one of the top 12 bio-based building blocks
listed by the U.S. Department of Energy.14-16 Also, HMF has
been demonstrated as a promising sustainable raw material
and utilized in the synthesis of various interesting molecules.17-
of water, the formed HMF was rehydrated to form levulinic
acid and formic acid, hence loss in selectivity and yield. Use of
organic medium is constrained by limited solubility of fructose.
In an exceptional case, fructose is easily soluble in DMSO, but
the extraction of HMF becomes very tedious when DMSO is
used as a reaction medium.26-33 Also, the available methods
are constrained by many other shortcomings such as humin
formation,46-49 requirement of toxic and environmentally
incompatible catalysts,42 tedious process involved in the
preparation of catalysts50,51 and ionic liquids,52-55 energy
intense conventional/microwave heating23-45 etc. To expedite
our new methodology to access 21,23-dioxaporphyrins, we
wanted to develop a simple and selective method for HMF
synthesis from fructose by introducing the concept, solid
supported dehydration of fructose.
20
Conversion of biomass derived chemicals into value added
products is a topic of major interest towards sustainability.
Among the value added products, dioxaporphyrins are
interesting molecular skeleton capable of forming stable
complex with neutral atoms and nanoaggregates with good
charge mobility.21 Current synthesis of 21,23-dioxaporphyrins
involves complex synthetic procedures, low yield, and
difficulties in isolation.22 For the first time, we have designed a
very simple synthetic methodology to access 21,23-
dioxaporphyrins through furanylpyrrolyl carbinols utilizing
Here in we report a facile synthesis of HMF by dehydration
of fructose on solid support under very mild conditions at
room temperature. In a foray to utilize HMF as a sustainable
starting material in the synthesis of 21,23-dioxaporphyrin, we
have demonstrated the synthesis of two types of key
intermediates for accessing functionally tuneable 21,23-
dioxaporphyrins.
biomass derived HMF as a starting material (Scheme 1).
HMF is dehydrated form of fructose obtained in a Bronsted
acid catalyzed dehydration of fructose. In the available
methods for the dehydration of fructose, fructose was
dissolved in a medium and treated with a catalyst under
conventional or microwave heating. The reaction medium can
Results and Discussion
Our attempts to use HMF as a starting material in the
synthesis of core modified porphyrins were restricted by
difficulties in the synthesis of HMF, and the limiting factors
were (i) formation of polymeric material (humin) (ii)
rehydration of HMF in aqueous medium resulting levulinic acid
and formic acid and (iii) difficulties in extraction of HMF. To
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Journal Name
R
R
HO
H
OH
OH
O
N
N
O
Biomass /
Carbohydrates
HO
OH
O
HN
HO
CHO
– 3 H2O
O
O
HMF
OH
fructose
R = CH2NO2, Ph
key intermediates
R
21,23-dioxaporphyrin
Scheme 1. Synthesis of 21,23-dioxaporphyrin
address these issues, we started exploring solid phase (Table 1, entry 6) to reach HMF yield of 30%. When the
synthesis of fructose using readily available simple solid sample was kept at room temperature, very less amount of
supports (silica gel, celite and neutral alumina).
HMF (5%) was formed even after the period of 48 h (Table 1,
The initial exploration on solid supported dehydration was entry 7). Formation of HMF, albeit in traces (5%) at room
carried out under dry condition using silica gel as a solid temperature indicated that the dehydration could proceed in
support (Table 1). Silica gel is incompletely dehydrated room temperature itself and might proceed with better
polymeric structure with molecular formula SiO2·nH2O and efficiency if the content was stirred at room temperature in
capable of adsorption of water up to 35–40% of its dry mass. the presence of an organic solvent/medium. Also, the use of
Its surface comprises mainly -Si-OH and –Si-O-Si- groups solvent might facilitate the periodic extraction of HMF from
providing intrinsic polarity and absorbs polar adsorbates such solid support. Hence we designed a set of experiments,
as water and alcohol.56 Fructose by its inherent polarity was treating silica gel supported fructose with HCl (5 equiv) in the
adsorbed firmly on the silica gel surfaces. The loading was presence of dichloromethane as
carried out by mixing fructose and silica gel (1:1, by wt) in a temperature (Table 2, Figure 1).
a medium at room
mortar and pestle for 2–3 minutes.
In a wet synthesis using CH2Cl2 as a solvent carried out at
The solid supported fructose was treated with HCl (5 room temperature for 30 min, HMF was obtained as the only
equiv), mixed well by grinding and kept in a hot air oven product from solution fraction in very low yield (Table 2, entry
maintained at specified temperature for stipulated. Keeping at 1). Extending time to achieve enhanced yields of HMF did not
100 °C for 30 min resulted in the formation of HMF in 32% result in any increase in the HMF yields (Table 2, entries 2-7).
yield (Table 1, entry 1). The HMF was extracted by washing But, we noticed the formation of a non-polar compound and
the treated silica gel with ethyl acetate. Decrease in its yield was increased with increase in reaction time. The
temperature to 80 °C resulted in slight improvement in HMF compound was characterized as 5-chloromethylfurfural (CMF).
yield (36%, Table 1, entry 2). For the experiments carried out CMF is considered functionally equivalent to HMF and easy to
at 50 °C, five samples were prepared by mixing silica gel isolate from aqueous/biphasic solvent systems due to its
supported fructose with HCl (5 equiv) and the samples were lipophilicity.57 After 24 h stirring at 30 °C, CMF was obtained in
kept in a hot air oven maintained at 50 °C. Samples were 32% isolated yield. In an experiment carried out using HBr
removed from oven in a regular time interval as stipulated in instead of HCl, 5-bromomethylfurfural (BMF) was obtained in
Table 1 and washed with EtOAc to obtain HMF. Dehydration of 35 % yield (Table 2, entry 7) along with HMF in 10% yield.
fructose carried out at 50 °C required prolonged heating
Table 2. HMF synthesis on wet silica gel support at room temperature.a
Table 1. Solid supported dry synthesis of HMFa
O
O
fructose
(on silica)
CHO
CHO
HCl
CH2Cl2
HO
Cl
H
OH
O
O
HCl (5 equiv)
80 °C, dry
~36%
CHO
residual HMF
CMF
HO
OH
HO
entry
time (h)
yield (%)
HO
OH
HMF
residual HMF
CMF
total
entry
temperature (°C)
time (h)
HMF yield (%)
1
2
0.5
3
10
12
11
10
8
ꢀꢀ
10
15
18
23
32
35c
10
22
26
28
31
37
45
1
2
3
4
5
6
7
100
80
50
50
50
50
30
0.5
0.5
0.5
4
32
36
<5
10
15
30
5
3
4
6
9
5
12
24
24
12
24
48
6
7b
5
10
aFructose (1.8 g) and silica gel (230-400 mesh, 1.8 g) were mixed and treated with
aFructose (1.8 g) and silica gel (230-400 mesh, 1.8 g) were mixed and treated with CH2Cl2 (40 mL) and HCl (5 equiv) at room temperature. bHBr (5 equiv) was used
HCl (5 equiv) and kept at hot air oven.
instead of HCl. cValue corresponds to yield of 5-bromomethylfurfural (BMF).
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Table 3. Screening of solvent for the transformation HMF ꢀ BMFa
entry
solvent
HMF yield (%)
HMF recovered
BMF
1
2
3
4
5
6
dichloromethane
chloroform
dichloroethane
acetonitrile
THF
ꢀ
ꢀ
87
85
91
<5
<5
<5
ꢀ
90
93
94
dioxane
aA solution of HMF (1.00 mmol, 126 mg) in solvent (10 mL) was treated with conc.
HBr (2.9 mL, 25 mmol, 48% solution in water) for 24 h at 30 °C.
dehydration on solid support. In the dehydration experiments
carried out using halogenated solvents, BMF was obtained as
the major product (Table 4). All the halogenated solvents
tested showed similar trend in terms of yield and selectivity
(Table 4, entries 1-4). Reducing the HBr equivalences up to 2
did not show any change in the BMF yield (Table 4, entries 4-
6). Using HBr in less than 2 equivalences showed deterioration
in the fructose dehydration and BMF was obtained in lower
yields (Table 4, entries 7 & 8). Without addition of HBr, the
reaction did not proceed as evidenced by the absence of HMF
and BMF in the reaction mixture (Table 4, entry 9).
Figure 1. Yield comparison of CMF and residual HMF
Dependence of yield of CMF and residual HMF on reaction
time is graphically represented in Figure 1 to provide a clear
picture about this transformation. The whole transformation
(fructose
formation of HMF on solid phase (fructose
conversion of HMF CMF on liquid phase, leaving CMF and
ꢀ
CMF/BMF) can be divided in to two steps (i)
ꢀ
HMF) and (ii)
ꢀ
residual HMF in solution. The residual HMF yield increased
initially. On prolonged treatment, the residual HMF yield
In wet synthesis using non-halogenated solvents (MeCN,
dioxane & THF), HMF was obtained as the major product in
upto 80% yield (triple extraction) and BMF in traces (Table 5,
entries 1-3). This is in accordance with our expectance. In the
experiment carried out by treating solid supported fructose
decreased steadily as the transformation HMF ꢀ
kinetically faster than the transformation fructose
CMF was
HMF.
ꢀ
The CMF yield steadily increased with time in parallel with
total yield. The dehydration mediated by HBr followed similar
trend with slight betterment in the overall yield. BMF was
obtained as major product and HMF as minor product (Table 2,
entry 7).
Table 4. Dehydration of fructose in halogenated solventsa
Diminishing the formation of BMF might be beneficial in
developing simpler method of isolation of HMF. The available
literature reports on HBr/HCl mediated transformations of
HMF to BMF/CMF are utilizing only halogenated solvents
(dichloromethane DCM or dichloroethane DCE).58-60 This
implied that use of non-halogenated solvent as reaction
medium might stop the dehydration at HMF level. To support
this concept and to understand the reactivity of HMF with HBr,
entry
solvent
HBr equiv.
BMF yield (%)
1
2
3
4
5
6
7
8
9
dichloroethane
chloroform
5
5
5
30
32
30
35
33
33
22
11
NR
carbon tetra chloride
dichloromethane
dichloromethane
dichloromethane
dichloromethane
dichloromethane
dichloromethane
5
3
2
1
0.5
0
we tested HMF ꢀ
Our study on HMF
BMF transformation in various solvents.
ꢀ BMF transformation mediated by HBr
using different solvents concluded that HMF
ꢀ
BMF aFructose (1.8 g) and silica gel (230-400 mesh, 1.8 g) were mixed and treated with
halogenated solvent (40 mL) and HBr (5 equiv) at 30 °C for 12 h. NR = no reaction
transformation proceeded quantitatively, only in cases of
halogenated solvents (DCM, DCE & CHCl3) being used as a
solvent (Table 3, entries 1-3). In non-halogenated solvents
(THF, dioxane & acetonitrile), BMF was formed only in traces
and unreacted HMF was recovered (Table 3, entries 4-6).
These findings emphasized that HBr mediated dehydration
of fructose using non-halogenated solvent might stop at HMF
stage and provide HMF selectively. This is very conclusive
finding and provided us a crucial lead in tuning fructose
dehydration towards HMF selectivity. Accordingly, we
proceeded to screening of various solvents broadly
categorized as halogenated solvents (DCM, DCE & CHCl3) and
non-halogenated solvents (dioxane, THF, acetonitrile & ethyl
acetate) for HBr mediated fructose dehydration on solid
Table 5. HMF synthesis in non-halogenated solvents
entry
solvent
HMF yield (%)
single extractiona
triple extractionb
1
2
3
4c
5d
6
MeCN
dioxane
THF
36
39
37
45
33
21
78
74
80
95
75
59
THF
THF
EtOAc
aFructose (1.8 g) loaded on silica gel (230-400 mesh, 1.8 g) and solvent (40 mL)
were treated with HBr (5 equiv) at rt for 12 h. bStirring time is 3 x 8 h. cHBr loaded
on silica (1 equiv) was used. dExperiment using recovered silica support.
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Table 7. Screening of solid support for HMF synthesisa
with HBr preloaded on silica, HMF was obtained in 95% yield
(Table 5, entry 4). In a multiple extraction process, the solution
content of reaction medium was exchanged with fresh solvent
in an interval of 8 h, for three cycles. After three extractions,
the support was recovered, dried and reused for dehydration
and found to be effective in mediating the dehydration of
fructose as a fresh support (Table 5, entry 5). With ethyl
acetate being used as a solvent, HMF was obtained in slightly
lower yield along with formation of BMF and 5-
acetoxymethylfurfural (AMF) in traces (Table 5, entry 6).
entry
solid support
HMF yield (%)
1
2
3
4
5
6
7
Alumina
trace
trace
42
ꢀ
Celite
Silica gel (230ꢀ400 mesh)
Celite
45
74b,c
95b
Silica gel (230ꢀ400 mesh)
Silica gel (100ꢀ200 mesh)
78b
aFructose (1.8 g) and solid support (1.8 g) were mixed and treated THF (40 mL)
and silica supported HBr (1 equiv) for 12 h. btriple extraction (3 x 8 h). cConc. HBr
was used instead of solid supported HBr.
Our experimental observations concluded that HBr and HCl
were effective in mediating dehydration of fructose loaded on
solid support at room temperature and HMF was obtained up
to 95% isolated yield. In order to test the efficiencies of other
acids in mediating the dehydration, we have screened three
types of acids (Lewis acids, organic Bronsted acids and
inorganic Bronsted acids) and the results are tabulated in
Table 6. Lewis acids (AlCl3, Cu(NO3)2 & CuCl2·2H2O) and organic
Bronsted acids (benzoic acid, TsOH & trifluoroacetic acid) are
found to be ineffective in mediating the dehydration of
fructose. In the H2SO4 mediated reaction, the fructose was
found to be charred on the support. The screening of various
acids suggested the best condition as HBr mediated
dehydration of fructose at room temperature with triple
extraction procedure using HBr preloaded on silica.
Currently HMF has been utilized in the synthesis of
polymers, energy alternatives, solvent etc.14-20For the
synthesis of 21,23-dioxaporphyrins, we presumed that HMF
can be a well suited starting material to begin with. It has one
carbonyl group to introduce pyrrole moiety and another
carbonyl group in reduced form (-CH2OH) as a handle to build
tetra-pyrrole skeleton. In the proposed synthetic strategy
(Scheme 2A), HMF was treated with phenylmagnesium
bromide to form phenylfuranyldiol
1
in 85% yield.
Phenylfuranyldiol was treated with pyrrole (10 equiv) and
recyclable InCl3 (Table 8) in a solventless condition to form
phenyl-furanylpyrromethanecarbinol
2 in 67% yield, a key
The HMF synthesis was tested by using various readily
available solid supports (Table 7). In a parallel experiment
carried out using alumina, silica gel of different size, and celite
as solid support, alumina did not facilitate HMF formation
resulting only trace amount of HMF and BMF. The low yied of
HMF and its derivative was due to low conversion of fructose.
The absence of humin formation was evidenced by color and
TLC analysis of methanol washing of solid support (Table 7,
entry 1). In an experiment carried out with out solid support,
the fructose was settled in the bottom of reaction flask and
polymerization was induced (Table 7, entry 2). HMF selectivity
was observed only with celite and silica gel (Table 7, entries 3-
7). Better selectivity and yields were obtained using silica gel
with fine particle size (230-400 mesh), (Table 7, entries 6 vs 7).
intermediate for the synthesis of 21,23-dioxaporphyrin. To
study the recyclability of InCl3, the catalyst was loaded on
celite to make celite supported InCl3 (10% w/w) by thoroughly
mixing required amount of InCl3 and celite. In an experiment
to synthesize 2, after the completion of reaction (either at 30
°C for 18 h or at 70 °C for 30 min), the reaction medium was
diluted with dichloromethane and the catalyst was recovered
by centrifugation. The recovered catalyst was reused in the
synthesis of key intermediate
2 from 1 and found to be
effective for upto four cycles (Table 8, entry 6).
Table 6. Screening of acids for dehydration of fructosea
entry
acid
HMF yield (%)
1
2
Cu(NO3)2
NR
NR
CuCl2·2H2O
3
AlCl3
NR
4
pꢀtoluenesulfonic acid
4ꢀchlorobenzoic acid
trifluoroacetic acid
formic acid
NR
5
NR
6
NR
7
NR
8
9
hydrobromic acid
hydrochloric acid
Sulphuric acid
79b
64b
10
charred
aFructose (1.8 g) and silica gel (230-400 mesh, 1.8 g) were mixed and treated with
THF (40 mL) and acid (5 equiv) at 30 °C for 12 h. bTriple extraction (3 x 8 h). NR =
no reaction.
Scheme 2. Synthesis of 21,23-dioxaporphyrin
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Table 8. Screening of solid support for HMF synthesisa
provided by Merck. The spots were visualized by UV light or by
dipping into sulfuric acid in methanol (5%, v/v) and heated
with hot air gun. Column chromatography was carried out
using silica gel (230-400 mesh). All yields reported are of
isolated materials judged homogeneous by TLC, and NMR
spectroscopy. Parallel reactions are carried out in a Heidolph
StarFish Hei-End Multi Workstation. HMF produced by the
method reported in this article is used in the synthesis of key
entry
cycle number
fresh catalyst
I recycle
condition
Yield of 2 (%)
intermediates
3 and 4.
1
2
3
4
5
6
30 °C, 18 h
67
65
73
68
70
65
Synthetic Procedures
30 °C, 18 h
Preparation of solid supported fructose: Fructose (10 mmol,
1.8 g) and solid support (1.8 g) were taken in a mortar and
pestle and hand pulverized for 2-3 min. The content was
completely transferred to a reaction flask for dehydration
studies.
fresh catalyst
I recycle
70 °C, 30 min
70 °C, 30 min
70 °C, 30 min
70 °C, 30 min
II recycle
III recycle
aSolution of compound
1
(0.25 mmol, 51 mg) in pyrrole (2.5 mmol, 172
ꢀL) was
Experimental procedure for HBr mediated synthesis of HMF
on silica: Fructose (10 mmol, 1.8 g) loaded on silica gel (230-
400 mesh, 1.8 g) was taken in a reaction flask and THF (40 mL)
was added. The content was mixed with HBr supported on
silica (10 mmol, loaded onto 2.2 g silica) and the content was
stirred at 30 °C. After 8 h stirring, the solid matter was allowed
to settle down and the organic fraction was transferred to
another flask. The settled solid matter was mixed with fresh
THF (40 mL) and stirred for another 8 h. The process of stirring
and collection of solvent fraction was repeated to a total of 3
cycles. The combined organic fraction was treated with solid
sodium bicarbonate and filtered. The filtrate was evaporated
under reduced pressure. The resulting crude material was
purified by passing through a short silica pad [EtOAc/hexanes
(1:4)] to obtain HMF as yellow oily liquid (1.20 g, 95% yield).
Experimental procedure for HBr mediated conversion of HMF
to BMF: A solution of HMF (1.00 mmol, 126 mg) in solvent (10
mL) was treated with Conc. HBr (2.9 mL, 25 mmol, 48%
solution in water) in a flask, stirred for 24 h at 30 °C and then
organic layer was separated, and acidic fraction was extracted
with CH2Cl2 (for halogenated solvent) or EtOAc (for non-
halogenated solvent). Organic fractions were combined, dried
with Na2SO4. The solvent was removed by rotary evaporation
under reduced pressure and purified by passing through a
short silica pad.
treated with fresh/recovered celite supported InCl3 (25
condition.
ꢀmol) under stipulated
In an alternate route (Scheme 2B) to synthesize key
intermediate for dioxaporphyrin, HMF was treated with
nitromethane at 70 °C in the presence of ammonium acetate
yielding 5-(2-nitrovinyl)furan-2-ylmethanol
treatment of nitroalkene with pyrrole under solvent-less
condition in the presence of InCl3 resulted in the formation of
3 in 84% yield. The
3
5-(2-nitro-1-(pyrrol-2-yl)ethyl)furan-2-ylmethanol
yield.
4 in 62%
Conclusions
We have developed a conceptually designed and simple
method for the dehydration of fructose on a solid support
addressing several issues like selectivity, easy extraction,
diminishing the formation humin and rehydration of HMF. In a
solid supported dehydration of fructose mediated by acid
(HBr/HCl), HMF was selectively obtained as a major product in
>79% yield with other derivatives (BMF/CMF/AMF) in traces.
Use of non-halogenated solvent diminished the conversion of
HMF to BMF. The solid support and solvent used were
recovered and reused. Toward a sustainable era, we have
developed new synthetic methodologies to access key
intermediates to access functionally tunable 21,23-
dioxaporphyrins using plant derived HMF as starting material
and recyclable solid supported InCl3. These findings on easy
access to HMF and their use in organic synthesis will provide a
boost on exploration of HMF as sustainable raw material in
various organic syntheses.
Synthesis of (5-(hydroxymethyl)furan-2-yl)(phenyl)methanol
(1): A solution of HMF (10.0 mmol, 1.26 g) in THF (10 mL) was
treated with phenylmagnesium bromide (25 mmol, prepared
in a separate flask), stirred for 1 h. The excess Grignard
reagent was quenched by adding sat. aq. NH4Cl solution at 0
°C, extracted with EtOAc. Organic fractions were combined,
dried with Na2SO4. The solvent was removed by rotary
evaporation under reduced pressure and purified by passing
through a short silica pad to obtain the title compound as a
yellow solid (1.74 g, 85%): mp 90-92 °C; 1H NMR (300 MHz,
CDCl3) 4.57 (s, 2H), 5.81 (s, 1H), 6.02 (d, J = 3.0 Hz, 1H), 6.21
(d, J = 3.3 Hz, 1H), 7.29–7.46 (m, 5H); 13C NMR (75 MHz, CDCl3)
43.4, 76.6, 110.9, 119.0, 122.0, 129.7, 137.1, 152.6, 155.2,
177.4; ESI-MS obsd 227.0682, calcd 227.0679 (M+Na; M =
C12H12O3).
Experimental
General information
1H NMR (300 MHz) spectra were recorded on Bruker-300-
AVANCE II spectrometer, with chloroform-d as solvent and
tetramethylsilane (TMS) as reference (δ = 0 ppm). The
chemical shifts are expressed in downfield from the signal of
δ
internal TMS. Analytical thin layer chromatographic tests were
carried out on aluminium sheets coated with silica gel GF
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Synthesis of 5-(phenyl(pyrrol-2-yl)methyl)furan-2-ylmethanol
(2): A solution of (1.00 mmol, 204 mg) in pyrrole (10.0 mmol,
690 L) was treated with InCl3 (100 mol, 221 mg, 10% w/w on
Notes and references
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celite), stirred for 18 h at 30 °C. The content was diluted with
CH2Cl2 (10 mL) and the solution fraction was collected. The
residue was washed with CH2Cl2 (2 x 5 mL). The combined
solution fraction and washings was concentrated under
reduced pressure. The resulting residue was purified by
column chromatography [silica, EtOAc: hexanes (1:19)] to
3
obtain the title compound
2 as a white solid (170 mg, 67%):
1
mp 94-96 °C; H NMR (300 MHz, CDCl3) 4.50 (s, 2H), 5.42 (s,
1H), 5.90–5.92 (m, 1H), 5.98 (d, J = 3.3 Hz, 1H), 6.14 (q, J = 3.0
Hz, 1H), 6.20 (d, J = 3.3 Hz, 1H), 6.67–6.70 (m, 1H), 7.19–7.33
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by recrystallization from ethanol to give the title compound
3
1
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as yellow solid (1.42 g, 84 % yield): mp 84-86 °C; H NMR (300
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6.79 (d, J = 3.3 Hz, 1H), 7.45 (d, J = 13.2 Hz, 1H), 7.68 (d, J =
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Synthesis
ylmethanol (4): A solution of
(10.0 mmol, 690 L) was treated with InCl3 (200
of
5-(2-nitro-1-(pyrrol-2-yl)ethyl)furan-2-
(2.00 mmol, 338 mg) in pyrrole
mol, 442 mg,
3
ꢀ
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10% w/w on celite), stirred for 30 min at 30 °C. The content
was diluted with CH2Cl2 (10 mL) and the solution fraction was
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combined solution fraction and washings was concentrated
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obtain the title compound
4 as a light brown liquid (293 mg,
1
62%): H NMR (300 MHz, CDCl3) 4.54 (s, 2H), 4.75–5.00 (m,
3H), 6.07–6.09 (m, 1H), 6.12 (d, J = 3.3 Hz, 1H), 6.13–6.16 (m,
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259.0699, calcd 259.0689 (M+Na; M = C11H12N2O4).
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Acknowledgements
P.V. thanks the DST for DST-Fast Track Grant (No. SB/FT/CS-
003/2014). The authors thank the SASTRA University,
Thanjavur for providing lab space, NMR facility and TRR
Research grant. High Resolution Mass spectra were obtained
at School of Chemistry, University of Hyderabad, Hyderabad,
India.
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Facile synthesis of 5-hydroxymethylfurfural: A sustainable raw material for synthesis of
key intermediates toward 21,23-dioxaporphyrins
Rajamani Rajmohan, Subramanian Gayathri and Pothiappan Vairaprakash*
Department of Chemistry, School of Chemical and Biotechnology,
SASTRA University, Thanjavur, Tamil Nadu, India 613 4001
vairaprakash@scbt.sastra.edu