Niobium(V) chloride as catalyst in diels-alder reaction of furan ring

Article abstract of DOI:10.5935/0103-5053.20140052

According to the relevant literature, the Diels-Alder reaction of furan without a catalyst can last several weeks and shows a low yield due to the diene's low reactivity. The use of Lewis acid catalysts or high pressures is described as an effective method for improving the reaction yields. This paper describes our recent study on the use of niobium pentachloride as the catalyst in Diels-Alder reactions between furan and several reactive dienophiles, among which methyl acrylate showed good yields, especially at lower temperatures. Other dienophiles have shown lower yields because of problems such as byproduct formation and the high reversibility of the reaction.

Full text of DOI:10.5935/0103-5053.20140052

http://dx.doi.org/10.5935/0103-5053.20140052
J. Braz. Chem. Soc., Vol. 25, No. 5, 882-886, 2014.
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Article
A
Niobium(V) Chloride as Catalyst in Diels-Alder Reaction of Furan Ring
Deborah A. dos Santos,a Ludmila R. Rodrigues,a Bruno H. Arpini,a
Valdemar Lacerda Jr.,*,a Sandro J. Greco,a Reginaldo B. dos Santos,a
Álvaro C. Neto,a Wanderson Romãoa,b and Eustaquio V. R. de Castroa
aChemistry Department, Federal University of Espírito Santo,
Av. Fernando Ferrari, 514, 29075-910 Vitória-ES, Brazil
bFederal Institute of Education, Science and Technology of Espírito Santo,
Av. Ministro Salgado Filho, s/n, 29106-010 Vila Velha-ES, Brazil
De acordo com a literatura, a reação de Diels-Alder de furano sem uso de catalisador pode
durar várias semanas e apresenta baixo rendimento devido à baixa reatividade do dieno. O uso
de catalisadores ácidos de Lewis ou de altas pressões são descritos como métodos eficazes para
melhorar o rendimento da reação. Este trabalho descreve nosso estudo recente sobre a utilização
de pentacloreto de nióbio, como catalisador em reações de Diels-Alder entre furano e alguns
dienófilos reativos, entre os quais o acrilato de metila apresentou bons rendimentos, especialmente
sob temperaturas mais baixas. Outros dienófilos apresentaram rendimentos mais baixos devido a
problemas, tais como a formação de produtos secundários e de elevado caráter de reversibilidade
da reação.
According to the relevant literature, the Diels-Alder reaction of furan without a catalyst can
last several weeks and shows a low yield due to the diene’s low reactivity. The use of Lewis acid
catalysts or high pressures is described as an effective method for improving the reaction yields. This
paper describes our recent study on the use of niobium pentachloride as the catalyst in Diels-Alder
reactions between furan and several reactive dienophiles, among which methyl acrylate showed
good yields, especially at lower temperatures. Other dienophiles have shown lower yields because
of problems such as byproduct formation and the high reversibility of the reaction.
Keywords: niobium pentachloride, Diels-Alder, furan
Introduction
The Diels-Alder reaction of furan ring (1) with a
reactive dienophile (2) provides 7-oxabicyclo[2.2.1] hept-5-
ene (3), an important intermediate in the synthesis of several
natural products such as terpenes (4), prostaglandins (5),
shikimic acid (6), and its analogues (Scheme 1).1,2
Several researchers have described methods for
synthesizing these cyclic intermediates. The Diels-Alder
reaction using a furan ring is the simplest because it requires
a single reaction stage. However, furan has low reactivity
as a diene and requires the use of Lewis acid catalysts, high
pressures, or highly reactive dienophiles.Another problem
concerning this cycloaddition is how easily it undergoes a
reverse reaction – retro-Diels-Alder – due to the stability
Scheme 1. Synthesis of intermediate 7-oxabicyclo[2.2.1]hept-5-ene (3)
*e-mail: vljuniorqui@gmail.com
and natural products derived from it.

Vol. 25, No. 5, 2014
Santos et al.
883
of the diene. Therefore, high reaction temperatures are
often avoided.2
was stirred until a yellowish solution was achieved. Then,
11 mmol of diene (1) were slowly added, with the system
kept under constant agitation all along the reaction length.
The mixture obtained was diluted at the end of the reaction
with 75 mL of ethyl acetate. This solution was washed
with 100 mL of diluted sodium bicarbonate. The solvent
was evaporated, and the products obtained were analyzed
through IR spectroscopy and nuclear magnetic resonance
of ¹H (400 MHz) and ¹³C (100 MHz). The reactions yields
were calculated in terms of wt.%. The spectroscopic data
agreed with the reports in the literature.17-19 Ratios of
the endo and exo adducts were determined through the
relation of the integral of the ¹H NMR signals from the
corresponding double bond hydrogens of the endo and
exo adducts.
Recent studies have shown the potential gains of
using niobium compounds as Lewis acids in organic
synthesis compared to other inorganic compounds of
known acidity.3 The activity of niobium pentachloride
as a catalyst has been described in several reactions
such as epoxide opening,4-6 the Diels-Alder reaction,7,8
synthesis of pyranoquinoline derivatives,9 Mannich
reactions,10 syntheses of α-aminonitriles,11 arylation of
aromatic compounds,12 and cyanosilylation of carbonyl
compounds,13 among others.14,15 Most of the time, NbCl5
provided higher yields and selectivity compared to the
Lewis acids usually used in these reactions.
This study used niobium pentachloride as the Lewis
acid in synthesizing 7-oxabicyclo[2.2.1]hept-5-ene (3)
derivatives through the Diels-Alder reaction between
furan (1) and reactive dienophiles (2a-d) (Scheme 2) to
evaluate the catalyst activity in the reaction yields and the
selectivity of the products.
Results and Discussion
The niobium pentachloride activity as a catalyst was
investigated in Diels-Alder reactions between furan (1)
and several reactive dienophiles – methyl acrylate (2a),
acrylonitrile (2b), dimethyl maleate (2c), and 2-chloro-
acrylonitrile (2d) – (Scheme 2) changing reaction parameters
such as temperature, catalyst ratio, and reaction length.
The reactions were carried out without solvents, initially
because the diene and dienophiles were liquid and to
contribute to the application of environmentally friendly
methodologies in organic synthesis, implying minimum
residue generation, whereas the Diels-Alder reaction does
not generate side products, and during the extraction of the
adduct, the NbCl5 is hydrolyzed, providing Nb2O5.nH2O,
which has low toxicity.
Scheme 2. The Diels-Alder reaction between furan (1) and several reactive
dienophiles (2a-d).
Experimental
First, the optimum conditions for the reaction between
furan (1) and methyl acrylate (2a) were studied (Table 1).
Then, the ideal catalyst ratio was determined: 0.5 and
2.5 mol% of NbCl5 showed some activity in 24 reaction
hours at different temperatures, whereas with 10 mol% of
the catalyst, for the same reaction length, the yields were
good (42-77%), especially at lower temperatures.
The Diels-Alder reaction is reversible, and due to the
easy way in which cycloadditions with 1 undergo a reverse
reaction, we started a study on the ideal reaction length
using 10 mol% of the catalyst. Shorter times increased the
yields, and temperature was again an important factor in
the conversion rates; the lower the temperature, the higher
the yields. In general, product selectivity was higher for
the endo adduct in all reaction conditions.
The starting materials are commercially available and
were used without purification, except for furan, which
was treated and distilled according to the literature.16
Infrared (IR) spectra were recorded on a FTLA2000-
102-ABB BOMEM FT-IR spectrophotometer using Pike
Technologies MIRacle Single Reflection ATR accessory,
45°, ZnSe, using atmosphere as blank. 1H and 13C nuclear
magnetic resonance (NMR) spectra were recorded using a
Varian 400 (400 MHz) spectrometer with tetramethylsilane
(TMS) as the internal standard.
General experimental methods
The reactions were carried out in anhydrous medium,
because NbCl5 is easily hydrolyzed. Ten millimoles of
dienophile (2a-d) were added to a sealed round bottom
flask with NbCl5 (0.05, 0.25, and 1.0 mmol). The mixture
Comparing the best result achieved for the reaction
between furan (1) and methyl acrylate (2a) catalyzed by
NbCl5 to what has been reported in the literature (Table 2),
higher product yields were achieved under shorter reaction

884
Niobium(V) Chloride as Catalyst in Diels-Alder Reaction of Furan Ring
J. Braz. Chem. Soc.
Table 1. Yields and the endo:exo ratio for reactions between furan (1) and methyl acrylate (2a)
entry
Diene
Dienophile
time
24 h
Temperature / °C
r.t.
NbCl5 / mol%
Yield / % (endo:exo)
1
1
2a
0.5
2.5
10
2 (63:37)
16 (51:49)
42 (57:43)
3 (66:34)
2
3
4
0
0.5
2.5
10
5
22 (65:35)
75 (59:41)
3 (61:39)
6
7
–20
0.5
2.5
10
8
21 (65:35)
77 (60:40)
50 (59:41)
59 (62:38)
85 (61:39)
58 (57:43)
75 (65:35)
99 (58:42)
47 (61:39)
81 (58:42)
83 (62:38)
9
10
6 h
4 h
2 h
r.t.
0
10
11
12
–20
r.t.
0
13
10
10
14
15
–20
r.t.
0
16
17
18
–20
r.t.: room temperature.
Table 2. Comparison of methodologies for synthesizing 3a described in the literature with the best result achieved when NbCl5 is used
Catalyst
NbCl5
–
Solvent
Temperature / °C
time
4 h
Yield / % (endo:exo)
99 (58:42)
–
–
–20
40
r.t.
60
40
–78
5
1-2 months
4 h
50 (85:15)20
62 (–b)21
a
–
CH2Cl2
CH2Cl2
–
a
–
6 h
95 (60:40)22
55 (33:67)23
65 (67:33)24
76 (70:30)25
41 (70:30)25
ZnI2
48 h
HfCl4
Et2O
–
17 h
BF3.OEt2
BF3.OEt2
10 h
CCl4
5
14 h
aPressure of 15 kbar; bnot informed by the author. r.t.: room temperature.
time and without using solvent. Most methods reported
show higher selectivity for the endo adduct compared to
our results.
Although the dienophilicity of dimethyl maleate (2c)
is increased due to the β-carboalkoxy group, reactions
using 2c as the dienophile did not show any conversion
even in the presence of up to 10 mol% of NbCl5 in 24 h,
at room temperature or 0 °C. Tests using the solvent
(CH2Cl2) were unsuccessful. At these temperatures, retro-
Diels-Alder must be favored, Hayashi et al.24 observed
higher yields and selectivity in reactions carried out at
–20 and –50 °C using HfCl4 as the Lewis acid catalyst.
Thus, experiments at lower temperatures were performed
to try to improve the results.
When acrylonitrile (2b) was used as the dienophile
(Table 3), low yields were achieved even with 10 mol%
of NbCl5 and at low temperatures. A problem observed
during this reaction was the formation of byproducts
mainly at –20 °C, possibly resulting from polymerization
of acrylonitrile. Reaction times shorter than those used in
the reaction between 1 and 2a were tested to try to decrease
the byproduct formation; however, our attempts were
unsuccessful. Adduct selectivity was in general lower than
that observed for product 3a.
For reactions between furan (1) and 2-chloro-
acrylonitrile (2d) (Table 5), we adopted conditions that had
provided good conversion rates for other adducts. Since 2d
is a more reactive dienophile, two catalyst ratios were tested
Reaction times longer than those we used are required
to achieve higher yields for product 3b as shown in Table 4.

Vol. 25, No. 5, 2014
Santos et al.
885
Table 3. Yields and the endo:exo ratio for reactions between furan (1) and acrylonitrile (2b)
entry
1
Diene
Dienophile
time
24 h
Temperature / °C
r.t.
NbCl5 / mol%
Yield / % (endo:exo)
4 (50:50)
6 (52:48)
6 (50:50)
7 (50:50)
6 (49:51)
9 (50:50)
3 (–)a
1
2b
0.5
2.5
10
2
3
4
0
0.5
2.5
10
5
6
7
–20
0.5
2.5
10
8
8 (–)a
9
11 (–)a
10
11
12
13
14
15
16
17
18
2 h
1 h
r.t.
0
10
14 (58:42)
3 (57:43)
6 (56:44)
18 (57:43)
8 (57:43)
6 (59:41)
7.5 (51:49)
14.3 (59:41)
14.2 (60:40)
–20
r.t.
0
10
10
–20
r.t.
0
40 min
–20
aOnly byproducts were observed in the ¹H NMR spectrum. r.t.: room temperature.
Table 4. Comparison of methodologies for synthesizing 3b described in
the literature with the best result achieved when NbCl5 is used
(2.5 and 10 mol%) for 2 hours of reaction. In general, the
yields were low. At 0 °C and –20 °C the yields were higher
with 10 mol% of catalyst. At room temperature, however,
the yields were lower with higher amounts of catalyst
(entry 2, Table 5). To explain this behavior, the reaction
was carried out for 1 and 4 h, and the yields achieved were
12 and 6%, respectively. Thus, a reverse reaction is favored
by time under this temperature, which can also justify the
higher ratio of the exo adduct.
The yields obtained for 3d were lower than those
achieved using other Lewis acids (Table 6). However,
higher selectivity for the exo adduct was observed when
NbCl5 was used.
Yield / %
Catalyst
Temperature / °C
time
(endo:exo)
18 (57:43)
25 (61:39)26
55 (-b)21
NbCl5
–
r.t.
30
1 h
5 weeks
4 h
a
–
r.t.
ZnI2
40
48 h
48 h
3 h
100 (50:50)24
35 (57:43)27
48 (55:45)28
90 (65:35)28
ZnI2c
40-60
r.t.
ZnCl2
ZnCl2/SiO2
r.t.
3 h
aPressure of 15 kbar; bnot informed by the author; cZnI2 used in excess.
r.t.: room temperature.
Table 5. Yields and the endo:exo ratio for reactions between furan (1) and 2-chloro-acrylonitrile (2d)
entry
Diene
Dienophile
time
2 h
Temperature / °C
r.t.
NbCl5 / mol%
Yield / % (endo:exo)
18 (20:80)
1
1
2d
2.5
10
2
10 (23:77)
3
0
2.5
10
2 (39:61)
4
19 (24:76)
5
–20
2.5
10
8 (41:59)
6
20 (34:66)
r.t.: room temperature.

886
Niobium(V) Chloride as Catalyst in Diels-Alder Reaction of Furan Ring
J. Braz. Chem. Soc.
Table 6. Comparison of methodologies for synthesizing 3d described
in the literature
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Chem. 2003, 40, 369.
Yield (%)
Catalyst
Temperature / °C
time
(endo:exo)
20 (34:66)
11 (–)a,17
7. Constantino, M. G.; Lacerda Jr.,V.; da Silva, G.V. J.; Molecules
2002, 7, 456.
NbCl5
–20
70
2 h
18 h
4 weeks
48 h
3 h
–
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–
26
33 (71:39)18
60 (50:50)24
30 (67:33)28
55 (38:62)28
ZnI2
40
ZnCl2
ZnCl2/SiO2
r.t.
r.t.
3 h
aNot informed by the author. r.t.: room temperature.
11. Majhi, A.; Sung, S. K.; Kim, H. S.; Appl. Organomet. Chem.
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Conclusions
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NbCl5 has been shown to be an active catalyst for
the Diels-Alder reaction between furan (1) and methyl
acrylate (2a), with good yields and reasonable selectivity
for the endo adduct. When the dienophile was dimethyl
maleate (2c), NbCl5 had no activity. In the reactions that
used acrylonitrile (2b) as the dienophile, lower yields
and selectivity were achieved, and byproducts formed.
With 2-chloro-acrylonitrile (2d), the yields were also low;
however, higher selectivity for the exo adduct was observed.
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Supplementary data (NMR and FTIR spectra) are
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The authors thank CBMM for providing the niobium
pentachloride used in this work, Conselho Nacional
de Desenvolvimento Científico e Tecnológico (CNPq),
Coordenadoria de Aperfeiçoamento de Pessoal do Nível
Superior (CAPES), and Fundação de Amparo à Pesquisa
do Espírito Santo (FAPES) for financial support.
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Submitted: December 14, 2013
Published online: March 14, 2014