Hydroformylation of dihydrofurans catalyzed by rhodium complex encapsulated hexagonal mesoporous silica

Article abstract of DOI:10.1016/j.molcata.2015.01.027

HRh(CO)(PPh₃)₃ encapsulated hexagonal mesoporous silica (HMS) is found to be an efficient heterogeneous catalyst for the selective hydroformylation of 2,3-dihydrofuran (2,3DHF) and 2,5-dihydrofuran (2,5DHF). The Rh-complex encapsulated in situ in the organic phase of template inside the pores of HMS was found to act as nano phase reactors. Conversion of 2,3-DHF and 2,5-DHF and selectivity of the corresponding aldehydes were thoroughly investigated by studying the reaction parameters: catalyst amount, substrate concentration, partial as well as total pressure of CO and H₂, and temperature. The selectivity for the formation of tetrahydrofuran-2-carbaldehyde (THF-2-carbaldehyde) from the hydroformylation of 2,3-DHF was found to be more than the selectivity of the formation of tetrahydrofuran-3-carbaldehyde (THF-3-carbaldehyde) from 2,5-DHF. The reaction paths are suggested and discussed for the selective formation of the corresponding aldehydes. The catalyst was elegantly separated and effectively recycled for six times.

Full text of DOI:10.1016/j.molcata.2015.01.027

Accepted Manuscript
Title: Hydroformylation of dihydrofurans catalyzed by
rhodium complex encapsulated hexagonal mesoporous silica
Author: Munir D. Khokhar Ram S. Shukla Raksh V. Jasra
PII:
S1381-1169(15)00042-4
DOI:
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http://dx.doi.org/doi:10.1016/j.molcata.2015.01.027
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30-10-2014
24-1-2015
Please cite this article as: Munir D.Khokhar, Ram S.Shukla, Raksh V.Jasra,
Hydroformylation of dihydrofurans catalyzed by rhodium complex encapsulated
hexagonal mesoporous silica, Journal of Molecular Catalysis A: Chemical
http://dx.doi.org/10.1016/j.molcata.2015.01.027
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Hydroformylation of dihydrofurans catalyzed by rhodium complex encapsulated
hexagonal mesoporous silica
Munir D. Khokhar1, Ram S. Shukla*, Raksh V. Jasra*2
Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals
Research Institute, Council of Scientific and Industrial Research (CSIR), G.B. Marg,
Bhavnagar – 364 002, Gujarat, India.
1Present address: KAUST Catalysis Center (KCC), King Abdullah University of Science
& Technology, 23955-6900 Thuwal, Kingdom of Saudi Arabia.
2Present address: R&D Center, Vadodara Manufacturing Division, Reliance Industries
Limited, Vadodara, Gujarat, India.
* Corresponding author: Tel.: +91 278 2567760; fax: +91 278 2566970,
E–mail addresses: rshukla@csmcri.org (Ram S. Shukla) and rakshvir.jasra@ril.com
(Raksh V. Jasra)
1

ABSTRACT
HRh(CO)(PPh3)3 encapsulated hexagonal mesoporous silica (HMS) is found to be an
efficient heterogeneous catalyst for the selective hydroformylation of 2,3-dihydrofuran
(2,3DHF) and 2,5-dihydrofuran (2,5DHF). The Rh-complex encapsulated in situ in the
organic phase of template inside the pores of HMS was found to act as nano phase
reactors. Conversion of 2,3-DHF and 2,5-DHF and selectivity of the corresponding
aldehydes were thoroughly investigated by studying the reaction parameters: catalyst
amount, substrate concentration, partial as well as total pressure of CO and H2, and
temperature. The selectivity for the formation of tetrahydrofuran-2-carbaldehyde ( THF-
2- carbaldehyde) from the hydroformylation of 2,3-DHF was found to be more than the
selectivity of the formation of tetrahydrofuran -3-carbaldehyde (THF-3-carbaldehyde)
from 2,5-DHF. The reaction paths are suggested and discussed for the selective formation
of the corresponding aldehydes. The catalyst was elegantly separated and effectively
recycled for six times.
Keywords:
Hydroformylation, Furans, Heterogeneous, Aldehydes, Hexagonal mesoporous silica.
2

1. Introduction
Furan and its derivatives have enormous potential applications and used as a
chemical building blocks for the production of fine chemicals, pharmaceutical
intermediates and pesticides [1-4]. The major furan based drugs being manufactured in
pharmaceutical industries are Ranitidine, Prazosin, Furosemide, Cefuroxime,
Sulphamethoxazole and Cefoxtin [5-9]. The important uses of these drugs are curing
hypertension and congestive heart failure. Furan has a remarkable importance in the
preparation of natural as well as synthetic pesticides because furan molecule is the key
intermediate in the natural pesticide known as wyerone [10]. Pyrethrin [11] is another
important pesticide among furan based pesticides. Intermediates for these products can be
obtained by functionalizing the furan side chain selectively in the second position by
utilizing various reactions like catalytic hydrogenation, hydroformylation,
hydroformamination and oxidation routes. The literature is scanty for the
functionalization of second position of the side chain of furan via catalytic
hydroformylation in which rhodium complex is used as a catalyst along with syn-gas in
homogeneous conditions [12–14].
Hydroformylation of furans [15] to hydroxymethyl tetrahydrofurans have been
reported in modest yield using Co2(CO)8 catalyst. In the hydroformylation reaction,
rhodium complexes have been found to be better catalysts [16] than cobalt based catalysts.
HRh(CO)(PPh3)3 and RhCl(CO)(PPh3)2 complexes have been reported to perform as
effective catalysts for the hydroformylation of dihydrofurans under homogeneous
conditions [12]. Noteworthy investigation in the hydroformylation of 2,3-dihydrofuran
3

(2,3-DHF) and 2,5-dihydrofuran (2,5-DHF) in liquid phase had been reported by Lapidus
et al. [17].
Investigations on the selective introduction of formyl group on the second and
third position of the tetrahydrofuran, starting from 2,3-DHF and 2,5-DHF respectively,
have been reported [18]. In these reactions the modifications have been made in the
employed reaction conditions and the ligands. Homogeneous hydroformylation is known
for high selectivity and is used in the syntheses of fine chemicals and derivatives. The
main draw backs associated with homogeneous hydroformylation are the separation of
products from the solvent, high separation and catalyst cost. Numerous efforts have been
made in the field of hydroformylation wherein the precious metal containing catalyst can
be recovered from the reaction mixtures [19–23].
Wilkinson catalyst has remained the important homogeneous catalyst for the
hydroformylation reaction, as it offers high activity and selectivity for the reaction
[24,25]. In our wide research programme on utilization of carbon monoxide in recent
investigations, rhodium based catalysts were heterogenized and were found to be
effective catalysts for hydroformylation [26–31,32,33] and hydroaminomethylation
[34,35]. Immobilization [36] is one such route which can help the homogeneous catalyst
to stay inside the porous materials and help prevent leaching or loss. Rhodium complex
encapsulated into the mesopores of hexagonal mesoporous silica was found to act as
nanophase reactor [26,37] in the catalytic hydroformylation of the double bond of the
linear C5–C12 alkenes under heterogeneous conditions. The main advantages in using
HMS are its large wall thickness, small scattering domain sizes, complementary textural
mesoporosities and thermal stability [38].
4

In the present paper the work was carried out to investigate the performance of
HRh(CO)(PPh3)3 encapsulated hexagonal mesoporous silica (HRh(CO)(PPh3)3–HMS)
catalyzed heterogeneous hydroformylation of 2,3-DHF and 2,5-DHF, which are
heterocyclic and important for pharmaceutical intermediates and pesticides. The catalyst
is investigated in detail and the reaction parameters such as catalyst amount, total as well
as partial pressure of CO and H2, substrate amount and temperature effect on the
hydroformylation were studied.
2. Experimental
2.1. Synthesis of the catalyst
Complex HRh(CO)(PPh3)3 [39], hexagonal mesoporous silica (HMS) [38] and the
catalyst, HRh(CO)(PPh3)3 impregnated into HMS (HRh(CO)(PPh3)3−HMS) [26] were
synthesized and characterized (see supplementary information and figures S1-S7) by the
reported procedures. The precise descriptions of their synthesis are as follows.
2.1.1. Synthesis of HRh(CO)(PPh3)3 complex
A solution of RhCl3.3H2O (2.0 g, 7.6 mmol) in ethanol (70 mL) was added to a
refluxing solution of triphenylphosphine, PPh3 (12 g, 46.0 mmol) in ethanol (300 mL).
After 2 min. aqueous formaldehyde (10 mL) was added drop wise and the solution turned
yellow with the formation of trans-RhCl(CO)(PPh3)2. Addition of sodium borohydride,
(2.0 g) in ethanol to the above hot mixture yielded the yellow crystals of Rh-complex.
The unreacted rhodium metal was removed by washing the yellow crystal with ethanol.
2.1.2. Synthesis of HMS
5

In a typical synthesis procedure 0.0027 mol of hexadecyl amine was dissolved in a
mixture of 0.0909 mol of ethanol and 0.296 mol of deionised water. The solution was
stirred at room temperature (RT) on a magnetic stirrer. To this stirring solution 0.01 mol
of TEOS was added drop wise and mixture was kept for 1 h at RT. After 1 h, the white
gel precipitate was formed, which was kept at RT for 18 h of aging. The material was
filtered and washed with 1:1 (v/v) ethanol-water mixture and dried in vacuum at RT.
2.1.3. Synthesis of HRh(CO)(PPh3)3-HMS
For the synthesis of HRh(CO)(PPh3)3–HMS (Rh-HMS), the in situ
encapsulation of the HRh(CO)(PPh3)3 into the HMS pores was done as follows. In a
typical synthesis procedure, 0.0027 mol of hexadecyl amine was dissolved in a mixture of
0.0909 mol of ethanol and 0.296 mol of deionised water. The solution was stirred on a
magnetic stirrer. To this stirring solution 0.07 mmol of HRh(CO)(PPh3)3 was added. To
this suspension 0.01 mol of TEOS was added drop wise. Stirring was continued for 1 h
and a pale yellow precipitate was formed, which was kept for 18 h for aging at RT. The
yellow precipitate was filtered and washed with 1:1 (v/v) ethanol-water mixture and dried
in vacuum at RT. The catalyst was calcined in air at 300 ºC prior to its characterization.
ICP analysis of HRh(CO)(PPh3)3-HMS gave 0.6 wt% of rhodium [26] in which the ratio
of Rh-complex: TEOS was 3 wt%.
2.1.4. Hydroformylation and product analysis
The reaction was carried out in 100 mL bench top stirred reactor (Parr Reactors,
USA; model No. 4843) having controlling unit and digital display for stirring speed and
reaction temperature. In a typical experimental procedure, desired amount of the catalyst
6

(HRh(CO)(PPh3)3–HMS) was added to 50 mL toluene as a solvent along with the
substrate and n-decane as internal standard in the reactor. Carbon monoxide gas was fed
before adding hydrogen to the system in order to avoid unnecessary hydrogenation of the
substrate. Both the gases, CO and H2 were fed to the required ratio followed by gradual
increase in the temperature and the reaction was initiated by stirring the reaction mixture
at 600 rpm. Liquid samples were withdrawn periodically through the sampling valve
during the reactions and were analyzed using GC and GC–MS instruments equipped with
flame ionization detector (FID). The GC oven temperature was programmed from 40 to
200 °C at the rate of 10 °C min-1. N2 was used as the carrier gas in GC and helium gas
was used in GC–MS. Conversion of substrates and selectivity of the products was
calculated from the % area of the GC report.
3. Results and discussions
3.1. Effect of the amount of the catalyst on the hydroformylation
Effect of the amount of the catalyst on the hydroformylation of 2,3-DHF and 2,5-
DHF were studied at varied catalyst amount from 20 mg to 200 mg as depicted in Fig. 1.
The conversion as well as selectivity gradually increases in both the cases. Maximum
conversion of 99% with 90% selectivity of tetrahydrofuran-2-carbaldehyde (THF-2-
carbaldehyde) was achieved with 200 mg of the catalyst in the case of 2,3-DHF. The
conversion of 2,5-DHF to tetrahydrofuran-3-carbaldehyde (THF-3-carbaldehyde) attained
saturation at 91% with 72% selectivity. The conversion and selectivity in the case of the
hydroformylation of 2,3-DHF were comparatively higher than those of 2,5-DHF. The
7

observed increased conversion of 2,3-DHF and 2,5-DHF is due to the availability of more
active rhodium species at higher amount of the catalyst.
3.2. Effect of pressure on the hydroformylation
Firstly effect of total pressure (10 to 30 atm.) on the conversion and selectivity,
for the hydroformylation of 2,3-DHF and 2,5-DHF was studied and the results are
depicted in Fig. 2. At lower pressure, lower conversion of substrate and lower selectivity
of aldehydes was obtained. Conversions were increased on increasing the total pressure,
whereas the selectivity attained saturation on further increasing the total pressure.
Partial pressures of CO (pCO) and H2 (pH2) play a vital role in the
hydroformylation reactions. Experiments were carried out for observing the effect of
pCO and pH2 on the hydroformylation of 2,3-DHF and 2,5-DHF and the corresponding
results are given in Tables 1 and 2 respectively. The effects of pCO on the
hydroformylation of 2,3-DHF were studied by varying the pCO from 5 to 50 atm. at
constant pH2 , 15 atm. The conversion of 2,3-DHF (Table 1) increased from 55 to 98% on
increasing the pCO from 5 to 15 atm. On further increasing the pCO up to 50 atm., the
conversion remained nearly constant. The variation of the pCO was observed to be
ineffective on the selectivity of THF-2-carbaldehyde. Similar to the variation of pCO, the
pH2 was varied from 5 to 50 atm. The conversion of 2,3-DHF increased from 52 to 98%
on increasing the pH2 from 5 to 15 atm. On further increasing the pH2 the conversion
remained constant at ~98%. Unlike the variation of the pCO, a decreasing trend in the
selectivity of THF-2-carbaldehyde was observed on increasing the pH2.
The hydroformylation of 2,5-DHF (Table 2) was carried out under the identical
conditions of 2,3-DHF and on increasing the CO pressure from 5 to 20 atm. the
8

conversion was observed to increase from 50 to 98%. The conversion remained constant
(98%) on increasing pCO up to 50 atm. The selectivity of THF-3-carbaldehyde remained
almost constant on varying the pCO under the present employed reaction conditions. The
conversion was increased from 49 to 98% on increasing pH2 from 5 to 25 atm. Similar to
2,3-DHF, the selectivity of the product, THF-3-carbaldehyde in the case of the
hydroformylation of 2,5-DHF was observed to decrease on increasing pH2. A comparison
of the selectivity of the hydroformylation product indicated that the selectivity for the
formation of THF-3-carbaldehyde was less than that of THF-2-carbaldehyde, on variation
of pCO as well as pH2. The observed effects of total pressure and pCO on the
hydroformylation of these substrates are addressable in terms of the mechanistic [40]
concern associated with the formation of the Rh-acyl species and β-elimination. On
increasing the total pressure and pCO, more availability of CO makes the insertion of CO
more favourable than β-elimination, which in turn becomes feeble to affect the selectivity.
The decreasing trend in the selectivity towards higher pH2 for both the substrates may be
due to the favourabilty of isomerization [26] by the higher H2 environment.
3.4. Effect of 2,3- and 2,5-DHF concentration
Effect of the variation of the concentration of 2,3-DHF and 2,5-DHF on their
hydroformylation have been studied by varying the concentration of substrate from 2.26 x
10-2 M to 27.21 x 10-2 M (2,3-DHF) and 2.34 x 10-2 M to 28.08 x 10-2 M (2,5-DHF) and
the respective results are given in Table 3 and 4. The conversion and selectivity during
the hydroformylation of 2,3-DHF remained almost constant upto 9.07 x 10-2 M and of
2,5-DHF remained upto 9.36 x 10-2 M. On further increasing the concentration of 2,3-
DHF, gradual decrease in the conversion and selectivity was observed. Similar trend of
9

decrease in the conversion and selectivity was observed in the case of the
hydroformylation of 2,5-DHF. The decrease in conversions are in the line of the
observations [30,37] of substrate inhibition behaviour towards higher concentration. As
the amount of the substrate increased, the rhodium species required for higher
conversion, may be found to be in scarcity which in turn can lead to decrease the
conversion.
3.5. Effect of reaction temperature
Studies were carried out in the range of 60 to 140 °C as depicted in the Fig. 3. The
conversion was found to increase up to 100 °C for both the substrates and further increase
in temperature could not affect the conversion. Percentage selectivity for the formation of
THF-2-carbaldehyde from 2,3-DHF was more than the formation of THF-3-carbaldehyde
from 2,5-DHF in the entire studied range of the temperature. Decreasing trends in the
selectivity were observed for both the substrates on increasing the temperature above
80 °C. This is indicative of the occurrence of significant effect on the β-elimination
process. The increase in temperature can effectively cause a fast pre-equilibrium between
Rh-alkyl species through β-elimination [40], which will decrease the selectivity towards
the corresponding aldehydes.
3.6. Reaction paths
The main product of the hydroformylation of 2,3-DHF is THF-2-carbaldehyde
and of the hydroformylation of 2,5-DHF is THF-3-carbaldehyde (Scheme 1). In our
investigations it is observed that the selectivity for the formation of THF-2-carbaldehyde
from the hydroformylation of 2,3-DHF is more than the selectivity of the formation of
10

THF-3-carbaldehyde from 2,5-DHF. This is explainable in terms of the extent of less
isomerization of 2,3-DHF to 2,5-DHF [41,42] and the concerned mechanistic path
[40,43] for the hydroformylation of 2,3-DHF and 2,5-DHF.
The overall mechanistic paths during the reaction involving hydroformylation and
quite possible isomerizations are proposed in Scheme 2. The Rh metal, of
HRh(CO)(PPh3)3 encapsulated into mesopores HMS acting as nanophase reactors, reacts
individually with the olefinic bond of 2,3-DHF/2,5-DHF thereby forming the
corresponding pi-bond coordinated species 1/3. Beta-hydride eliminations from 1/3 make
the occurrence of equilibria between 1/3 and the corresponding Rh alkyl (2-alkyl, 2/ 3-
alkyl, 4) intermediates. The competent favourability and extent of the formation of 2 and
4 contributes towards the formations of THF-2 carbaldehyde and THF-3 carbaldehyde
respectively. The Rh-C bond formed in 3-alkyl (4) associated with the higher electron
density than the Rh-C bond formed in 2-alkyl (2) species, thermodynamically favoured
[40,43] the formation of 4. Also, the C-3 –Rh bond in the 3-alkyl intermediate being less
polarizable than the C-2–Rh bond in the 2-alkyl intermediate, causes the formation of the
further acyl complex less quickly from the 3-alkyl than from the 2-alkyl Rh intermediate
(Scheme 2). Hence the comparative more quick formation of the acyl complex occurring
from the 2-alkyl intermediate contributed towards the formation of more THF-2-
carbaldehyde from the hydroformylation of 2,3-DHF than the formation of THF-3-
carbaldehyde.
3.8. Reusability of the catalyst
After the completion of the hydroformylation reaction, the catalyst was separated
by simple filtration and washed with warm water. The filtrate was analyzed by
11

inductively coupled plasma with atomic emission spectra (ICP-AES) in order to check
the leaching of Rh content. The rhodium content in the filtrate was found to be 0.015 ppm
which confirmed the negligible leaching of the rhodium. The results of the reusability of
the catalyst for the hydroformylation of 2,3-DHF and 2,5-DHF are depicted in the Table
5 and Table 6 respectively. The conversion of 2,3-DHF was 98% with 89% selectivity of
THF-2-carbaldehyde with the fresh catalyst (cycle 1) which at the end of sixth cycle was
94% and 84% respectively (Table 5). Similar was the case for 2,5-DHF, in which the
fresh catalyst gave 90% conversion with 72% selectivity and 86% conversion with 68%
selectivity of THF-3-carbaldehyde was obtained in sixth cycle. These reusability results
showed that the catalyst is effectively reusable for six cycles without significant loss in
the conversion and selectivity. A marginal loss in activity may be due the loss of Rh-
complex situated on the outer surface of the catalyst upto little extent, during filtration
and washing processes, since Rh-complex which is in the nanopores will not be affected
during filtration and washing, but those which are on the outer surface of the HMS may
get lost during reusability.
It is of interest to have a comparative insight in to the performance of the
heterogeneous, HRh(CO)(PPh3)3–HMS catalyst , with closely related catalysts systems
(Table 7) for the hydroformylation. HRh(CO)(PPh3)3−HMS catalyzed heterogeneous
hydroformylation of 2,3-DHF ( Entry 6) gave 98% conversion and 89% selectivity for
THF-2-carbaldehyde in 12 h at 80 °C at total pressure of CO and H2 at 30 atm. Both
conversion and selectivity obtained were lower, at higher employed temperature (range,
90-120°C) and pressure (range, 870 - 1000 psig (= 59.20-68.04 atm.)) for the reported
[12] Rh based homogeneous (Entries 1-3,5) as well as heterogeneous (Entry 4) catalyst
12

systems than the present (Entry 6) catalyst system. For homogeneous hydroformylation
of 2,5-DHF, at 750 psig (= 51.03 atm.) 100% conversion with 95% selectivity (Entry 7)
and 97% conversion with 84% selectivity at 30 bar pressure in 12 h ( Entry 8) were
obtained. Heterogeneous hydroformylation of 2,5-DHF by HRh(CO)(PPh3)3−HMS
(Entry 9) gave 90% conversion with 72% selectivity in 12 h at 30 atm. These
comparisons indicated that the performance of HRh(CO)(PPh3)3−HMS is better for
hydroformylation of 2,3-DHF in the terms of the conversion, selectivity and lower
temperature and pressure. Also the HRh(CO)(PPh3)3−HMS catalyst is effectively
recycled for both the substrates 2,3-DHF and 2,5-DHF.
4. Conclusions
HRh(CO)(PPh3)3 encapsulated in the pores of HMS as a heterogeneous catalyst
showed effective catalytic performance for the hydroformylation of 2,3-DHF and 2,5-
DHF to corresponding aldehydes selectively. Under the employed experimental
conditions the conversion of 2,3-DHF was 98% with 89% selectivity of THF-2-
carbaldehyde, and 90% conversion with 72% selectivity of THF-3-carbaldehyde was
obtained for 2,5-DHF. Both conversion and selectivity were influenced on increasing the
catalyst amount and total pressure. Increase in temperature, pCO and pH2 afforded an
enhancement in conversions. The selectivity to THF-2-carbaldehyde from the
hydroformylation of 2,3-DHF was found to be more than the selectivity to THF -3-
carbaldehyde from 2,5-DHF and explained in the terms of the suggested reaction paths. A
comparative insight indicated that the performance of HRh(CO)(PPh3)3−HMS is better
for hydroformylation of 2,3-DHF in the terms of the conversion, selectivity and lower
13

temperature and pressure. The HRh(CO)(PPh3)3−HMS catalyst is effectively recycled for
both the substrates 2,3-DHF and 2,5-DHF.
Acknowledgment
Authors thank Council of Scientific and Industrial Research (CSIR), New Delhi, India,
for financial supports for Network Project for the Development of Specialty Inorganic
Materials for Diverse Applications.
14

References
[1] K.L. Zeng, F. Alali, L.L. Rogers, F. Wu, S. Sastrodihardjo, J.L. Mclaughlin,
Phytochemistry 38 (1998) 565-571.
[2] Z. Sajadi, M. Almahmood, L.J. Loeffler, I.H. Hall, J. Med. Chem. 22 (1979)
1419-1422.
[3] C. Bailly, R. Houssin, J. Bernier, J. Henichart, Tetrahedron 44 (1988) 5833-5843.
[4] M.E. Hensler, G. Bernstein, V. Nizeta, A. Nefzib, Bioorg. Med. Chem. Lett. 16
(2006) 5073-5079.
[5] L.B. Hough, W.M.P.B. Menge, A.C. van de Stolpe, J.W. Nalwalk,R. Leurs, I.J.P.
de Esch, Bioorg. Med. Chem. Lett. 17 (2007) 5715-5721.
[6] J.C.L. Erve, S.C. Vashishtha, W. DeMaio, R.E. Talaat, Drug Metab. Dispos. 35
(2007) 908-916.
[7] P. Butler, D. Williams, R. Jones, L. Randle, A. Payne, M. Howard, I. Gardner, J.
Blagg, D. Smith, B.K. Park, Drug Met. Rev. 38 (2006) 1-187.
[8] N. Can, G. Altiokka, Y. Hassan, A. Enein, Analytica Chimica Acta 576 (2006)
246-252.
[9] E. Mavromanolakis, S. Maraki, G. Samonis, Y. Tselentis, A. Cranidis, J.
Chemotherapy 9 (1997) 203-207.
[10] A.G. Fallis, Synlett. 13 (2004) 2249-2267.
[11] C.D. Klaassen, M.O. Amdur, J. Doull, (Eds.) Casarett & Doull’s Toxicology. The
Basic Science of Poisons (5 ed.) Toronto: th McGraw-Hill Companies, Inc. 1996.
[12] D.E. Vietti, US Pat. 43,76,208 (1983).
15

[13] T. Hoiuchi, T. Ota, E. Shirakawa, K. Nozaki, H. Takaya, J. Org. Chem. 62 (1997)
4285-4292.
[14] I. del Rio, P.W.N.M. van Leeuwen, C. Claver, Can. J. Chem. 79 (2001) 560-565.
[15] G.O. Evans, C.U. Pittman, Jr., R. Mcmillan, R.T. Beach, R. Jones, J. Organomet.
Chem. 67 (1974) 295-314.
[16] V.K. Srivastava, D.U. Parmar, R.V. Jasra, Chemical Weekly Part 1: Commercial
Aspects, July 8 (2003) 173; Part 2: Technology, July 15 (2003) 181; Chemical
Economic Handbook, Oxo Chemicals Report, SRI International, 2003.
[17] A.L. Lapidus, L.Y. Brezhev, M.M. Vartanyan, Bulletin of the Academy of
Sciences of the USSR Division of Chemical, 38 (1989) 1091-1092.
[18] A. Polo, C. Claver, S. Castillon, A. Ruiz, J.C. Bayon, J. Real, C. Mealli, D. Masi,
Organometallics 11 (1992) 3525-3533.
[19] K. Kunna, C. Muller, J. Loos, D. Vogt, Angew. Chem. Int. Edn. 45 (2006) 7289-
7292.
[20] B. El Ali, J. Tijani, M. Fettouhi, M. El-Faer, A. Al-Arfaj, Appl. Catal. A: Gen.
283 (2005) 185-196.
[21] J. Balue, J.C. Bayon, J. Mol. Cat. A: Chem. 137 (1999) 193-203.
[22] I. Kani, R. Flores, J.P. Fackler, Jr., A. Akgerman, J. of Supercritical Fluids 31
(2004) 287-294.
[23] B. Lucke, A. Kockritz, K.-D. Vorlop, S. Bischoff, M. Kant, Topics in Catal. 29
(2004) 111-118.
[24] D. Evans, J.A. Osborn, G. Wilkinson, J. Chem. Soc. (A) 12 (1968) 3133-3134.
16

[25] C.D. Frohning, C.W. Kohlpaintner, in: B. Cornils, W.A. Hermann (Eds.). Applied
Homogeneous Catalysis with Organometallic Compounds, Vol. 1, VCH,
Weinheim, 1996. 29ff.
[26] N. Sudheesh, S.K. Sharma, R.S. Shukla, R.V. Jasra, J. Mol. Cat. A: Chem. 296
(2008) 61-70.
[27] V.K. Srivastava, S.K. Sharma, R.S. Shukla, R.V. Jasra, Cat. Commun. 7 (2006)
879-884.
[28] R.V. Jasra, V.K. Srivastava, R.S. Shukla, H.C. Bajaj, S.D. Bhatt, U.S. Pat.
72,94,745 B2 (2007).
[29] S.K. Sharma, V.K. Srivastava, R.S. Shukla, P.A. Parikh, R.V. Jasra, New J. Chem.
31 (2007) 277-286.
[30] V.K. Srivastava, S.K. Sharma, R.S. Shukla, R.V. Jasra, Ind. Engg. Chem. Res. 47
(2008) 3795-3803.
[31] S.K. Sharma, R.S. Shukla, P.A. Parikh, R.V. Jasra, J. Mol. Catal. A: Chem. 304
(2009) 33-39.
[32] N. Sudheesh, J.N. Parmar, R.S. Shukla, Applied Catal. A General 415-416 (2012)
124-131.
[33] N. Sudheesh, A.K. Chaturvedi, R.S. Shukla, Applied Catal. A General 409-410
(2011) 99-105.
[34] N. Sudheesh and R.S. Shukla, Applied Catal. A General 453 (2013) 159-166.
[35] N. Sudheesh and R.S. Shukla, Applied Catal. A General 473 (2014) 116-124.
[36] A. Sassolas, J. Blum and D. Leca-Bouvier, Biotech. Advances 30 (2012) 489-511.
[37] N. Sudheesh, Sumeet K. Sharma, R. S. Shukla, R. V. Jasra, J. Mol. Catal. A.
17

Chem. 316 (2010) 23–29.
[38] P.T. Tanev, T.J. Pinnavaia, Science 267 (1995) 865-867.
[39] D. Evans, G. Yagupsky, G. Wilkinson, J. Chem. Soc. A. (1968) 2660-2665.
[40] I.D.Rio,P.W.N.M. van Leeuwen, C.Claver, Can.J.Chem. 79 (2001)560-565.
[41] A. Polo, J. Real, C. Claver, S. Castillon, J.C. Bayon, J. Chem. Soc.
Chem.Commun. (1990) 600-601.
[42] M. Dieguez, O. Pamies, C. Claver, Chem. Commun. (2005) 1221-1223.
[43] I.Ojima, K.Kato, M.Okabe, T.Fuchikami, J.Am.Chem.Soc.109 (1987) 7714-7720.
18

Figure captions:
Fig.1. Effect of the catalyst amount on the hydroformylation: substrate concentration =
9.07 x 10-2 M (2,3-DHF)/ 9.36 x 10-2 M (2,5-DHF), pCO = 15 atm., pH2 = 15 atm., temp.
= 80 °C, reaction time = 12 h.
Fig.2. Effect of total pressure on the hydroformylation: substrate concentration = 9.07 x
10-2 M (2,3-DHF)/ 9.36 x 10-2 M (2,5-DHF), catalyst = 100 mg, temp. = 80 °C, reaction
time = 12 h.
Fig.3. Effect of reaction temperature on the hydroformylation: substrate concentration =
9.07 x 10-2 M (2,3-DHF)/ 9.36 x 10-2 M (2,5-DHF), catalyst = 100 mg, pCO = 15 atm.,
pH2 = 15 atm., reaction time = 12 h.
19

90
75
60
2,3-DHF conversion
% selectivity THF-2-carbaldehyde
2,5-DHF conversion
% selectivity THF-3-carbaldehyde
0
40
80
120
160
200
Catalyst amount, mg
Fig.1. Effect of the catalyst amount on the hydroformylation: substrate concentration =
9.07 x 10-2 M (2,3-DHF)/ 9.36 x 10-2 M (2,5-DHF), pCO = 15 atm., pH2 = 15 atm., temp.
= 80 °C, reaction time = 12 h.
20

100
90
80
70
60
50
2,3-DHF conversion
% selectivity THF-2-carbaldehyde
2,5-DHF conversion
% selectivity THF-3-carbaldehyde
10
15
20
25
30
Total pressure, atm.
Fig.2. Effect of total pressure on the hydroformylation: substrate concentration = 9.07 x
10-2 M (2,3-DHF)/ 9.36 x 10-2 M (2,5-DHF), catalyst = 100 mg, temp. = 80 °C, reaction
time = 12 h.
21

100
95
90
85
80
75
70
65
60
55
2,3-DHF conversion
% selectivity THF-2-carbaldehyde
2,5-DHF conversion
% selectivity THF-3-carbaldehyde
60
80
100
120
140
Temperature, oC
Fig.3. Effect of reaction temperature on the hydroformylation: substrate concentration =
9.07 x 10-2 M (2,3-DHF)/ 9.36 x 10-2 M (2,5-DHF), catalyst = 100 mg, pCO = 15 atm.,
pH2 = 15 atm., reaction time = 12 h.
22

Table captions:
Table 1 Effect of pCO and pH2 on the hydroformylation of 2,3-DHF.
Reaction conditions: substrate concentration = 9.07 x 10-2 M, catalyst = 100 mg,
a
HRh(CO)(PPh3)3 : TEOS ratio = 5, temp. = 80 °C, reaction time = 12 h. for THF-2-
carbaldehyde.
Table 2 Effect of pCO and pH2 on the hydroformylation of 2,5-DHF.
Reaction conditions: substrate concentration = 9.36 x 10-2 M, catalyst = 100 mg,
a
HRh(CO)(PPh3)3 : TEOS ratio = 5, temp.= 80 °C, reaction time = 12 h. for THF-3-
carbaldehyde.
Table 3 Effect of concentration of 2,3-DHF on the hydroformylation.
Reaction conditions: catalyst = 100 mg, HRh(CO)(PPh3)3 : TEOS = 5, pCO = 15 atm.,
pH2 = 15 atm., temp. = 80 °C, reaction time = 12 h, for THF-2-carbaldehyde.
Table 4 Effect of concentration of 2,5-DHF on the hydroformylation.
Reaction conditions: catalyst = 100 mg, HRh(CO)(PPh3)3 : TEOS = 5, pCO = 15 atm.,
pH2 = 15 atm., temp. = 80 °C, reaction time = 12 h, a for THF-3-carbaldehyde.
Table 5 Reusability of HRh(CO)(PPh3)3-HMS for hydroformylation of 2,3-DHF.
Reaction conditions: substrate concentration = 9.07 x 10-2 M, catalyst = 100 mg,
a
HRh(CO)(PPh3)3 : TEOS ratio = 5, temp. = 80 °C, reaction time = 12 h. for THF-2-
carbaldehyde.
Table 6 Reusability of HRh(CO)(PPh3)3-HMS for hydroformylation of 2,5-DHF.
Reaction conditions: substrate concentration = 9.36 x 10-2 M, catalyst = 100 mg,
a
HRh(CO)(PPh3)3 : TEOS ratio = 5, temp. = 80 °C, reaction time = 12 h. for THF-3-
carbaldehyde.
Table 7 Comparison with closely related catalyst systems.
23

Table 1
Effect of pCO and pH2 on the hydroformylation of 2,3-DHF.
Entry
CO
atm.
5
H2
atm.
15
2,3-DHF
% Conversion % Selectivity a
1
2
55
70
98
98
97
98
98
98
52
75
98
90
90
89
90
91
90
90
90
89
89
86
10
15
20
25
35
40
50
15
15
15
15
15
15
15
15
15
15
5
3
4
5
6
7
8
9
10
11
10
20
12
13
14
15
15
15
15
15
25
35
40
50
97
98
98
98
85
83
81
80
Reaction conditions: substrate concentration = 9.07 x 10-2 M, catalyst = 100 mg,
a
HRh(CO)(PPh3)3 : TEOS ratio = 5, temp. = 80 °C, reaction time = 12 h. for THF-2-
carbaldehyde.
24

Table 2
Effect of pCO and pH2 on the hydroformylation of 2,5-DHF.
Entry
CO
atm.
5
H2
atm.
15
2,5-DHF
% Conversion % Selectivity a
1
2
50
68
90
98
98
98
98
98
49
69
97
74
73
72
73
72
73
73
73
73
72
68
10
15
20
25
35
40
50
15
15
15
15
15
15
15
15
15
15
5
3
4
5
6
7
8
9
10
11
10
20
12
13
14
15
15
15
15
15
25
35
40
50
98
98
98
98
66
63
60
59
Reaction conditions: substrate concentration = 9.36 x 10-2 M, catalyst = 100 mg,
a
HRh(CO)(PPh3)3 : TEOS ratio = 5, temp.= 80 °C, reaction time = 12 h. for THF-3-
carbaldehyde.
25

Table 3
Effect of concentration of 2,3-DHF on the hydroformylation.
Entry [2,3-DHF]
x 102 M
2,3-DHF
% Conversion % Selectivity a
1
2
3
4
5
2.26
99
99
98
85
72
90
90
89
87
86
4.53
9.07
18.14
27.21
Reaction conditions: catalyst = 100 mg, HRh(CO)(PPh3)3 : TEOS = 5, pCO = 15 atm.,
pH2 = 15 atm., temp. = 80 °C, reaction time = 12 h, a for THF-2-carbaldehyde.
26

Table 4
Effect of concentration of 2,5-DHF on the hydroformylation.
Entry [2,5-DHF]
x 102 M
2,5-DHF
% Conversion % Selectivity a
1
2
3
4
5
2.34
91
90
90
81
68
71
71
72
70
69
4.68
9.36
18.72
28.08
Reaction conditions: catalyst = 100 mg, HRh(CO)(PPh3)3 : TEOS = 5, pCO = 15 atm.,
pH2 = 15 atm., temp. = 80 °C, reaction time = 12 h, a for THF-3-carbaldehyde.
27

Table 5
Reusability of HRh(CO)(PPh3)3-HMS for hydroformylation of 2,3-DHF.
Cycles
Conversion of 2,3-DHF
% Selectivity a
1
2
3
4
5
6
98
97
96
96
95
94
88
87
87
86
85
84
Reaction conditions: substrate concentration = 9.07 x 10-2 M, catalyst = 100 mg,
a
HRh(CO)(PPh3)3 : TEOS ratio = 5, temp. = 80 °C, reaction time = 12 h. for THF-2-
carbaldehyde.
28

Table 6
Reusability of HRh(CO)(PPh3)3-HMS for hydroformylation of 2,5-DHF.
Cycles
1
Conversion of 2,5-DHF
90
% Selectivity a
71
2
3
4
5
6
89
88
88
87
86
70
70
69
69
68
Reaction conditions: substrate concentration = 9.36 x 10-2 M, catalyst = 100 mg,
a
HRh(CO)(PPh3)3 : TEOS ratio = 5, temp. = 80 °C, reaction time = 12 h. for THF-3-
carbaldehyde.
29