Solvent-free aminolysis of aliphatic and aryloxy epoxides with sulfated zirconia as solid acid catalyst

Article abstract of DOI:10.1016/j.apcata.2014.08.024

Single-step and two-steps synthetic procedure for the synthesis of sulfated zirconia (SZ) was developed, which were calcined at 500, 600 and 700 °C and characterized by various physico-chemical methods such as PXRD, FTIR, surface area, microanalysis, NH3-TPD and DRIFT analysis. These SZ materials were then employed as solid acid catalysts for the aminolysis of different aliphatic/aromatic terminal, aryloxy and meso epoxides with aromatic and aliphatic amines under ambient conditions. Amongst the catalyst prepared, SZ-2-600 prepared in two-steps and 600 ° C calcined was found to be the most efficient catalyst to give p-amino alcohols in up to 98% yield and 7gt;99% regioselectivity. The SZ catalyst was successfully recycled and reused up to six catalytic runs with intact efficiency.

Full text of DOI:10.1016/j.apcata.2014.08.024

Accepted Manuscript
Title: Solvent-Free Aminolysis Of Aliphatic And Aryloxy
Epoxides With Sulfated Zirconia As Solid Acid Catalyst
Author: Arpan K. Shah Manish Kumar Sayed H.R. Abdi
Rukhsana I. Kureshy Noor-ul H. Khan Hari C. Bajaj
PII:
S0926-860X(14)00520-1
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.apcata.2014.08.024
APCATA 14961
To appear in:
Applied Catalysis A: General
Received date:
Revised date:
Accepted date:
10-2-2014
16-8-2014
19-8-2014
Please cite this article as: A.K. Shah, M. Kumar, S.H.R. Abdi, R.I. Kureshy, N.-
u.H. Khan, H.C. Bajaj, Solvent-free aminolysis of aliphatic and aryloxy epoxides
with sulfated zirconia as solid acid catalyst, Applied Catalysis A, General (2014),
http://dx.doi.org/10.1016/j.apcata.2014.08.024
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Highlights:
Solid sulfated zirconia (SZ) catalysts were prepared by one and two steps methods.
SZ catalysts were calcined at 500, 600 and 700 oC temperatures and characterized.
Catalyst SZ-2-600 (two steps, 600 oC calcined) was the most active in AoE reaction.
High yield (~98%) of product -amino alcohols was achieved in 30-360 min. at RT.
The SZ catalyst was recycled several times without loss in its activity.
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Graphical Abstract
R4
N
O
H
Catalyst
SZ-2-600
N
R3
HO
R1
R4
R1
R2
R3
R1 = Alkyl, Ph,
O-Alkyl
R3 = Ar,
R2
RT, Solvent free
Alkyl
R4 = H,
Alkyl
OCH2Ph,
Yield, up to 98%
Regioselectivity, >99%
R2 = H, Ph
Alkyl
2
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Solvent-free aminolysis of aliphatic and aryloxy epoxides with sulfated
zirconia as solid acid catalyst
Arpan K. Shaha, b, Manish Kumara, b, Sayed H. R. Abdi*a, b, Rukhsana I. Kureshya, b, Noor-
ul H. Khana, b, and Hari C. Bajaja, b
a Discipline of Inorganic Materials and Catalysis, Central Salt and Marine Chemicals Research
Institute (CSIR-CSMCRI), a unit of Council of Scientific and Industrial Research (CSIR), G. B.
Marg, Bhavnagar 364021 Gujarat, India, Tel: +91-0278 2567760, Fax: +91-0278-2566970
b Academy of Scientific and Innovative Research (AcSIR), CSIR-CSMCRI, Bhavnagar, Gujarat,
India
E-mail: shrabdi@csmcri.org
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ABSTRACT
Single-step and two-steps synthetic procedure for the synthesis of sulfated zirconia (SZ) was
developed, which were calcined at 500, 600 and 700 ºC and characterized by various physico-
chemical methods such as PXRD, FTIR, Surface area, microanalysis, NH3-TPD and DRIFT
analysis. These SZ materials were then employed as solid acid catalysts for the aminolysis of
different aliphatic/aromatic terminal, aryloxy and meso epoxides with aromatic and aliphatic
amines under ambient conditions. Amongst the catalyst prepared, SZ-2-600 prepared in two-
steps and 600 ºC calcined was found to be the most efficient catalyst to give -amino alcohols in
up to 98% yield and >99% regioselectivity. The SZ catalyst was successfully recycled and
reused up to six catalytic runs with intact efficiency.
Keywords: sulfated zirconia, one and two steps preparation method, aminolysis of epoxide, solid
acid catalyst, β-amino alcohols, aryloxy and aliphatic epoxides
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1. Introduction
Aminolysis of epoxides (AoE) is one among the most atom efficient methods to produce racemic
and non-racemic -amino alcohols, which are commonly found in natural and synthetic
molecules of commercial importance [1-6]. A real issue with AoE is regioselectivity, as either
carbon of a non-symmetric epoxide can react with the nucleophile to produce regioisomers (Fig.
1). Plenty of literature is available on AoE that include non-catalytic [7-10] and catalytic
approaches [5-6, 11-43] with moderate to high success. Noticeable results in AoE were achieved
with Brønsted [11-15] and Lewis acids [16-21] under homogeneous condition and with solid
acid materials [21-42] under heterogeneous condition with moderate to excellent yield and
selectivity of -amino alcohol. A closer look into the structure of -amino alcohol of commercial
importance would reveal that structural variations (substituents) on motifs (Fig. 1) originating
from epoxide as well as amine are prevalent. Therefore, a catalyst which can perform AoE
effectively for variety of aliphatic and aryloxy epoxides with variety of aromatic and aliphatic
amines is highly desirable and such efforts have been reported in the past with mixed success [5-
6, 9, 14, 18-21]. Here we report, synthesis of nano-sized sulfated zirconia (SZ) [40-51] having
super acidity/high acid strength, hydrothermal stability as solid acid catalyst for AoE. As such
SZ is a well-known solid acid catalyst for various commercially important organic
transformations [40-47]. In fact SZ has been used in the AoE under solvent free condition by G.
N-Silva et al. [40] and under microwave irradiation and by Reddy et al. [41] in high yields but in
later case the reaction took longer time. Das et al. [42] efficiently opened the epoxide ring with
substituted indoles via C-C bond forming reaction using SZ catalyst. Recently, Pathare et al. [6]
reported sulfated tungstate as potential solid acid catalyst for AoE of various epoxides with
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amines. However, in this case, catalyst preparation method required hazardous sulfonation
source-ClSO3H, chlorinated organic solvent and subambient reaction temperature (0-5 ºC).
Therefore, still there is a room to improve overall AoE process particularly in exploring wide
variety substrate ranges, developing easily synthesizable and recyclable catalysts for commercial
applications. It is well known in the literature that catalytic activity of SZ significantly depends
upon its texture properties, use of zirconium precursor, sulfating agent, types of preparation
method and activating temperature [43-51]. With this backdrop, we present here the synthesis of
sulfated zirconia catalyst by single-step and two-steps preparation methods using zirconium n-
propoxide (Zr(OC3H7)4) as a source of zirconium and sulfuric acid as a sulfating agent. The
resultant zirconia materials were calcined at different temperatures in order to achieve optimum
catalytic activity. In single-step method, SZ materials were prepared by sol-gel process of J. Oh.
et al. [46] with some modifications, where initially zirconium precursor was hydrolyzed
followed by in situ sulfation of the sol-gel obtained was carried out by the addition of sulfuric
acid. The solid obtained was dried at 120 ºC to give solid sulfated zirconia catalyst henceforth
known as SZ-1-120, which was further calcined at 500, 600 and 700 ºC temperatures giving
catalysts SZ-1-500, SZ-1-600 and SZ-1-700 respectively. In two-step process, the method of
Mishra et al. [47] was used, where in first step zirconium hydroxide was prepared by the
hydrolysis of (Zr(OC3H7)4) with ammonia followed by sulfation of zirconium hydroxide with
sulphuric acid in second step. Drying of the resultant powder at 120 ºC (SZ-2-120) and
subsequent calcination at 500, 600 and 700 ºC temperatures furnished catalysts SZ-2-500, SZ-2-
600 and SZ-2-700 respectively. As synthesized SZ materials were then employed as catalyst in
AoE under solvent free condition at RT. Among the SZ materials used, SZ-2-600, prepared in
two steps was found to have the best catalytic activity in terms of yield and selectivity of -
amino alcohol in short reaction time under solvent free condition at RT. The catalyst, SZ-2-600
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was also found to be effective for a variety of aliphatic cyclic or acyclic, aromatic and aryloxy
epoxides with aliphatic/aromatic primary and secondary amines. Since in most of the cases
product is either viscous liquid or solid, the catalyst after each catalytic cycle was easily
recovered by filtration/centrifugation with an appropriate solvent then dried for reuse. The
recovered catalyst showed no signs of loss in its performance even after six catalytic runs
studied.
2. Experimental
2.1 Materials and Methods
X-Ray Powder Diffraction studies were carried out using X’pert Mpd, PHILIPS and Empyrean
XRD systems from PANanalytical (Japan) within 2 theta range of 10-65 degrees using CuKα1
(= 1.54060 Å) at ambient temperature. Surface area and pore size distribution of SZ materials
were determined by nitrogen adsorption-desorption method at 77.35 K by using ASAP 2020
instrument, Micromeritics Inc., USA. All SZ samples were activated at 393 K under vacuum just
prior to measurements. FT-IR spectra were recorded on Perkin Elmer Spectrum GX
spectrophotometer (USA) using KBr window. JEOL, JEM-2100 microscope (Japan) was used
for transmission electron microscopic (TEM) analysis at 200KV using carbon coated copper
grid. For this SZ material was dispersed in ethanol and a drop of the dispersion was placed on
copper grid to determine the textural properties of the materials. Elemental analysis was done on
CHNS analyzer “ElementarVario MICRO Cube (Germany)”. Diffuse Reflectance FT-IR
spectroscopy (DRIFT) was used to determine the Brønsted/Lewis (B/L) acid ratio of pyridine
adsorpted SZ samples using Perkin Elmer GX equipped with DRIFT Selector accessory
o
(Graseby Specac, P/N 19900 series). The spectra were recorded at room temperature (27 C),
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150 oC and 250 oC after holding at each temperature for 10 min, thus allowing sufficient time for
pyridine desorption. NMR spectra were recorded on a Bruker F113V spectrometer (200 MHz
and 500 MHz, Switzerland) using TMS as an internal standard. GC analysis was done on GC-
2010AF APC instrument (Shimadzu, Japan) using BP-5 capillary column (SGE, USA). The
aminolysis products were purified by flash chromatography using silica gel 60-120 and 100-200
mesh purchased from s. d. Fine Chem. Ltd., India. Zirconium n-propoxide and various cyclic,
acyclic, aryloxy and meso epoxides, aromatic and aliphatic amines (substituted amines) were
purchased from Aldrich chemicals and used as received (USA).
2.2 Synthesis of sulfated zirconia (SZ) catalysts
Sulfated zirconia materials were synthesized by using single-step and two-step processes as
follows.
2.2.1 Single-step process for the synthesis of SZ catalysts
The single-step process [46] was slightly modified wherein Zr(OC3H7)4 (10 mL, 70% in n-
propanol) was diluted with 12.5 mL of n-propanol (up to 30 %) to which 1 N aqueous solution of
H2SO4 (20 mL) was added drop-wise under vigorous stirring within 30 min. and the resultant
reaction mixture was stirred for another 6 h. The white solid thus obtained was filtered and dried
at 120 ºC (SZ-1-120) followed by calcination at 500, 600 and 700 ºC for 4 h giving catalysts SZ-
1-500, SZ-1-600 and SZ-1-700 respectively.
2.2.2 Two-steps Synthesis of SZ catalysts
In the two-step processes [47], hydrolysis of (Zr(OC3H7)4) (30 wt.% solution in n-propanol) was
carried out by using aqueous ammonia. At pH 9-10 Zr(OH)4 gel was formed which was dried at
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110 ºC. In the second step, sulfation of Zr(OH)4 dried powder was carried out by using 15 mL/g
solution of 1 N H2SO4. White solid thus obtained was filtered and dried at 120 ºC (SZ-2-120)
overnight and calcined at 500, 600 and 700 ºC giving catalysts SZ-2-500, SZ-2-600 and SZ-2-
700 respectively.
2.2.3 Synthesis of zirconia- ZrO2
For the sake of comparison, unpromoted zirconia-ZrO2 was prepared by the calcination of
zirconium hydroxide at 350 ºC for 4 h.
2.3 Catalytic procedure for aminolysis of epoxide (AoE) using SZ catalyst
A solid SZ catalyst (20 mg), an epoxide (1 mmol) and an amine (1 mmol) were taken in a 5 mL
screw capped vial and stirred magnetically for a given time period (monitored by GC or TLC)
under solvent free condition at RT. On completion of the reaction, viscous liquid or solid product
obtained was treated with methanol (2 X 3 mL) and centrifuged for the complete removal of
organic compounds from the solid catalyst. The evaporation of solvent from the combined
organic layers furnished the crude product. A small fraction of the crude product was directly
injected to HPLC to find out the regioselectivity. The remaining portion of the crude mixture was
purified by flash column chromatography (hexane/ethyl acetate, 80:20) to get the major
13
regioisomer in pure form. The purified product was characterized by 1H and C NMR analysis.
The residue thus obtained from centrifugation was dried in air (2 h) and then at 200 ºC for 3 h to
get back the active catalyst (>97 % recovery) for the next catalytic run.
The characterization data of some ring opening products are given in Supplementary
Information.
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3. Results and Discussion
3.1 Catalyst characterization
3.1.1 Powder X-Ray Diffraction technique
PXRD patterns of different SZ catalysts prepared in single-step and two-step methods are shown
in Fig. 2 (A) and 2 (B) respectively. The SZ catalysts SZ-1-120 and SZ-2-120 (non-calcined)
and SZ-1-500 and SZ-2-600 (calcined at 500 and 600 ºC respectively) were found to have
amorphous nature irrespective of their synthetic methods. SZ catalyst prepared in a single-step
and calcined at 600 ºC (SZ-1-600) showed crystalline metastable tetragonal phase which was
transformed into more stable monoclinic phase when calcined at 700 ºC to give tetragonal and
monoclinic mixed phase (28:72) of the catalyst SZ-1-700. Noticeably phase transformation of
sulfated zirconia was found to be associated with the loss of impregnated sulfate ions [43-48], as
it can be seen in the loss of sulphur in elemental analysis (Table 1). SZ catalysts prepared in two
steps SZ-2-600 (calcined at 600 ºC) and SZ-2-700 (calcined at 700 ºC) showed the crystalline
reflections at 2 theta values 30.4, 35.3, 50.4, 59.4, 60.3, 63.0 and 74.7 of pure tetragonal phase
(JCPDS no. 88-1007). However, in this case no phase transformation was observed. Crystallite
sizes (Table 1) as calculated by applying the Scherrer equation to XRD reflections for catalysts
SZ-1-600 and SZ-1-700 were found to be ~30 nm, which were significantly higher than SZ-2-
600 and SZ-2-700 (~7 nm). Comparatively, the crystallite size of unpromoted zirconia was of the
order of ~49 nm. The size reduction of sulfated zirconia crystals is attributed to the presence of
impregnated sulfate ions, which is known to retard the growth of crystallite size in unpromoted
zirconia [43-44, 48].
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3.1.2 FT-IR studies
IR spectra (Fig. 3) of SZ samples showed broad bands in the range of 990-1220 cm-1 confirming
the successful impregnation of sulfate ions in the material. All the SZ samples show bands at
around 993, 1057, 1130 and 1212 cm-1 which are the characteristic peaks of bidented chelation
of sulfate ions due to S-O and S=O bonds [43-44, 47, 49]. The band appeared at ~993 cm-1 can
be attributed to the symmetric (1) vibrations of S-O bond while 1057, 1130 and 1212 cm-1 bands
are assigned to asymmetric (3) stretching frequencies of O-S-O bonds [49]. The ionic nature of
S=O imparts the Brønsted acid site to the SZ which enhance the acidity of the material and
thereby reinforcing catalytic activity. A broad peak around 3300 cm-1 and an intense peak ~1630
cm-1 are attributed to the stretching and bending vibrations of the water molecules respectively.
Due to the large population of sulfate groups in non-calcined sample SZ-1-120 and SZ-2-120
bands in this region were intense and merged to give a broad band. However, the intensity of
these peaks decreases on increasing the calcination temperature due to loss of sulfate groups
upon calcination which is in good agreement with the TGA analysis and sulfur values obtained
by microanalysis (Table 1).
3.1.3 Thermo Gravimetric analysis and Microanalysis
TG plots of all the catalysts demonstrated continuous reduction in % weight loss (Table 1; Fig.
S1 to S8 in Supplementary Information) from the material on increasing calcination temperature
can be attributed to the removal of water adsorbed and decomposition of sulfate groups from the
SZ materials. Non-calcined samples demonstrated higher initial weight loss between 100-250 ºC
due to desorption of water. Broadness in the graph at around 400 ºC was possibly due to the
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removal of water and oxygen from sulfate groups indicating the presence of strong acidic sites
[51]. Finally, a sharp weight loss observed at >550 ºC temperature due to the removal of sulfate
groups except for samples SZ-1-700 and SZ-2-700. Eventually, sulfur values of all the samples
were evaluated by microanalysis (Table 1), which showed same trend of continuous decrease in
sulphur content on increasing the calcination temperature consistent with TG analysis.
3.1.4 N2 adsorption-desorption isotherm studies
The results from the N2 adsorption-desorption isotherm study of SZ catalysts carried out at 77 K
are summarized in Table 1. Amorphous SZ-1-120, SZ-1-500, SZ-2-120 and SZ-2-500 catalysts
exhibited type-III hysteresis loop in the range P/Po = 0.4-0.5 confirming the macroporous
structure of the material (entries 2, 3, 6, 7). Moreover, these materials possess very low BET
surface area ~10 m2/g but high pore volumes (0.1-0.2 cc/g) possibly due to the presence of large
pores, which are populated with sulfate groups, thereby filling the pores of material except in the
case sample SZ-2-120-a typical characteristics for the samples bearing intra-particular porosity.
The crystalline SZ-1-600, SZ-1-700, SZ-2-600 and SZ-2-700 (entries 4, 5, 8, 9) materials
showed the type-IV hysteresis loop in the range P/Po = 0.4-0.5 suggesting the mesoporous
structure of these materials. Catalyst SZ-2-120 to SZ-2-700 materials show continuous reduction
in total surface area from 103 to 57 m2/g on increasing the calcination temperature, but no such
trend was seen in the case of SZ-1-120 to SZ-1-700 materials.
3.1.5 Ammonia-Temperature Programmed Desorption (NH3-TPD) technique
The strength and concentration of Brønsted or Lewis acidic sites of SZ catalysts were determined
by NH3-TPD technique to get an idea about types of acidic sites in SZ material (Fig. 4 (A), (B)
and Table 2). TPD graphs of catalysts prepared in single-step (Fig. 4 (A)) showed predominantly
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two types of the acidic sites; Lewis acidic sites at ~100 ºC as in SZ-1-600 and SZ-1-700 [44, 49-
51] and strong Brønsted acidic sites at 650 to 750 ºC as in SZ-1-500 and SZ-1-600. Brønsted
acid sites in SZ-1-500 showed unexpectedly intense peak in this region suggesting the presence
of large amount of sulfate groups on the surface. This peak marginally reduced when the
calcination temperature was raised from 500 to 600 ºC (SZ-1-600) and nearly disappears at 700
ºC (SZ-1-700) indicating the removal of sulfate ions coupled with phase transformation process
as is evident in PXRD patterns. Further, SZ-1-500 showed highest amount of total acidic sites
(3.22 mmol of NH3/g, Table 4.2), which reduces significantly to 0.5-0.2 mmol of NH3/g on
increasing the calcination temperature (SZ-1-600 and SZ-1-700; Table 2). Catalysts prepared in
two-steps showed markedly different TCD profile. Samples SZ-2-500 and SZ-2-700 (Fig. 4 (B))
showed weak acidic sites at ~100 ºC, and moderate Lewis and Brønsted acidic sites in the range
of 200-500 ºC [44, 51]. These peaks gradually diminished in catalysts SZ-2-500 to SZ-2-700 due
to continuous loss of sulfate ions upon calcination. Strong NH3-desorption peaks observed at
>500 ºC indicate the presence of strong Brønsted acidic sites of sulfate ions which in turn
enhances total acidity of catalyst and catalytic activity. Both the catalysts prepared by single-step
and two-steps processes showed similar trend in acid strengths when subjected to calcination at
different temperatures, similar results were also observed by Marakatti et al. [50]. Moreover,
total numbers of acid sites in SZ-2-500 (1.05 g/mmol) are fewer than SZ-2-600 (1.50 g/mmol)
but more than SZ-2-700 (0.55 g/mmol) because in former, the presence of surface sulfate groups
(Brønsted acid site) tend to masks the Lewis acid sites of the solid [44]. The increase in total
acidity from SZ-2-500 to SZ-2-600 is possibly due to the removal of some amount of sulfate
ions and thereby opening the face of Lewis acid sites inside the pores and on external solid
surface. The deconvoluted TPD graph of SZ-2-600 clearly show distribution of weak to
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moderate acidic sites in the temperature range of 200-550 ºC (Fig. S9, See Supplementary
Information).
3.1.6 DRIFT analysis
The DRIFT spectra of pyridine adsorbed SZ samples prepared in two steps (SZ-2-500, SZ-2-
600, SZ-2-700) showed characteristic bands at 1540 and 1612 cm–1 corresponding to Brønsted
acid sites while band at 1441 cm–1 corresponding to Lewis acidic sites (Fig. 5) [49]. The peak
area and B/L ratio (see Table S1, Supporting Information) exhibited similar trend as seen in
NH3-TPD experiments where initially this parameter increases from samples SZ-2-500 to SZ-2-
600 but decreased for SZ-2-700 suggesting that the Lewis acid character increases with decrease
in Brønsted acid character.
3.2 Catalytic Studies of SZ catalysts for AoE reaction
3.2.1 Optimization of the catalysts and its loading
The catalysis results of SZ catalyst AoE reaction using cyclohexenoxide and aniline as model
substrates at 1 mmol scale are summarized in Table 3. Zirconia and zirconium hydroxide (20
mg) gave moderate yields of -amino alcohol in 72 and 80% respectively under solvent free
condition at room temperature in 60 min. (entries 1, 2) indicating that the Brønsted acidity of the
catalyst enhances the yield of AoE reaction. While sulfate group incorporated SZ-1-120 and SZ-
1-500 catalysts increases product yield up to 85% (entries 3, 4) within 30 min showing the
influence of acid strength of the sulfated catalyst. However, catalysts SZ-1-600 and SZ-1-700
improved the yield of β-amino alcohol to 93 and 90% respectively (entries 5, 6) indicating that
acidity and surface area of the SZ catalysts are the driving factors for AoE reactions. Even
though the catalyst SZ-1-600 showed excellent activity initially, its activity dropped substantially
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on subsequent catalytic runs mainly due to the loss of sulphate ions as was evident from the loss
of sulphur content in the recycled catalyst. When non-calcined SZ-2-120 and calcined SZ-2-500
catalysts were used, an enhancement in yield 87% and 92% (entries 7, 8) was observed as
compared to catalysts SZ-1-120 and SZ-1-500, possibly due to higher surface area of the
catalysts prepared in two-steps. Moreover, when SZ-2-600 catalyst used, a significant
improvement in the product yield (96%, entry 9) was achieved, which was higher than the yield
obtained with SZ-2-700 catalyst (90%, entry 10) within 30 min. It is noteworthy that no
1
regioisomer was observed in H NMR in any of these cases. It is evident from the above results
that the catalyst SZ-2-600 is most efficient in terms of activity and selectivity for AoE reaction.
In order to find optimal catalyst loading, 15, 25 and 35 mg of catalyst SZ-2-600 per 1 mmol of
substrate were tested (entries 11-13). There was no lowering in the selectivity at 25 and 35 mg
catalyst loading, but there was a drop in overall yield of the product at higher catalyst loading
possibly due to stirring issues in the heterogeneous system. However, 20 mg catalyst per 1 mmol
of substrate was found to be the best to achieve the highest catalytic activity for AoE reaction.
3.2.2 Scope of various substrates for AoE reaction under optimized reaction condition
Above optimum reaction condition was then applied to aminolysis of various epoxides with
different amines using SZ-2-600 catalyst in 60 min. Interestingly, epoxide ring fused with five to
eight membered cycloalkanes gave a decreasing trend in the activity in AoE with the increase in
the ring size of cycloalkane from yield; 98 to 89%; (Table 4.4, entries 1-3), but cyclooctenoxide
(entry 4) failed to react with aniline possibly due to increasing steric repulsion caused by
hydrophobic methylene groups of cycloalkanes, which is higher in the case of cyclooctenoxide
molecule, thus resisting to the attack of nucleophile. In the case of aminolysis of
cyclohexenoxide with different substituted anilines, electron releasing groups such as methyl,
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ethyl, methoxy and chloro at different substituent positions on aromatic ring (entries 5-10)
furnished moderate to excellent yield (85-94%) of β-amino alcohol in 60 min. However, highly
electron withdrawing nitro group on aromatic ring, e.g. 4-nitroaniline fails to open the epoxide
ring (entry 11). This protocol was also found to be effective for the aminolysis of internal and
terminal aliphatic epoxides. Aminolysis of cis-butenoxide (entry 12) with aniline was found to be
more feasible than trans-butenoxide (entry 13) under the similar reaction condition possibly, as
stated earlier, due to the steric reasons. Aminolysis of 2-methylpropenoxide with aniline gave
88% yield of amino alcohol within 45 min (entry 14). The catalyst SZ-2-600 was also very
active for AoE of terminal aliphatic epoxides having carbon chain C4, C6, C8, C10, C12 and
C18 with aniline giving excellent yields of the respective ring opened products (90-96%, entries
15-20) within short reaction time. Aliphatic glycidyl ethers such as tertiarybutylglycidyl ether
and isopropylglycidyl ether also furnished good product yield (~90%) within 30 min. (entries 21-
22). Epichlorohydrine (entry 23) and epibromohydrine (entry 24) show almost full conversion
when reacted with aniline but gave lower yield of amino alcohol because of the formation of
chloro or bromo substituted products. Various aromatic glycidyl ethers were also tested for AoE
reaction with anilines where in phenylglycidyl ether (PGE) yielded 90% of β-amino alcohol
(entry 25). While 4-tertiarybutyl PGE and 4-chloro PGE gave products in quantitative yields
(entries 26-27). 4-Methoxy PGE (entry 28) and 2-methyl PGE (entry 29) afforded 90% yield of
the corresponding -amino alcohols in 30 min. using catalyst SZ-2-600. The efficacy of this
catalyst was then screened for aminolysis of PGE with aliphatic amines. AoE reaction of PGE
with branched aliphatic amine-isopropyl amine was relatively less regioselective (yield 82%,
entry 30) than its linear version n-propyl amine where only one regioisomer formed (yield 95%,
entry 31). Secondary amines with long alkyl chain e.g. in dioctlyamine gave epoxide ring opened
product only in moderate yield (68%, entry 32) possible due to higher hydrophobicity and steric
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constraints. SZ-2-600 catalyst was also found to be effective in AoE reaction of PGE with
heterocyclic amines such as piperidine and morpholine achieving excellent 94 and 97% yield of
β-amino alcohol respectively (entries 33-34). The synthesis of couple of drug molecules such as
(S)-Propranolol and (S)-Naftopidil via SZ-2-600 catalysed aminolysis of (S)-naphthylglycidyl
ether with isopropyl amine and 1-(2-methoxyphenyl)piperazine was achieved in 85 and 88%
yield respectively (entries 35-36) under solvent free condition with complete retention of
configuration suggesting that the present protocol does not trigger racemisation of chiral
epoxide. However, in the case of (S)-Propranolol regioselectivity was found to be 90:10 which
needs to be addressed for making this process commercially more acceptable. Ironically for the
reasons not know at this point of time, SZ-2-600 failed to catalyse ring opening reaction of cis-
stilbene oxide with aniline at RT and even at 60 ºC (entry 37).
From above results it can be clearly stated that the catalyst SZ-2-600 with highly crystalline
tetragonal phase, large surface area, super acidic strength and nano-scale size prepared via two-
steps processes and calcined at 600 ºC is optimum for the aminolysis of wide range of epoxide
with various amines.
3.2.3 Recycling of catalyst SZ-2-600 for AoE reaction under optimized reaction condition
Recyclability and reusability of SZ-2-600 for AoE reaction of cyclohexenoxide with aniline was
checked up to six catalytic runs in which the catalyst showed its intact efficiency in terms of
activity and selectivity as shown in Fig. 6. However, to get the consistent results from the used
catalyst, it was washed with methanol to remove any trapped product and starting materials and
then activated at 200 ºC for 3 h essentially to remove solvent molecules trapped inside the pores
of the catalyst before it was used for next catalytic run. The used catalyst after sixth use
17
Page 17 of 38

experiment was characterized by physico-chemical methods that showed similar characteristics
shown by the fresh catalyst.
4. Conclusions
Various grades of sulfated zirconia were prepared via single-step and two-steps processes and
calcined at different temperatures. Out of these SZ-2-600, synthesized in two-steps process and
calcined at 600 ºC was found to be the most active acid catalyst in the aminolysis of a wide range
of epoxides with various aliphatic and aromatic amines under solvent free condition at RT.
Parameters like highly crystalline and stable tetragonal phase, large surface area, strength and
higher fraction of super acidic sites and nano-scale of the catalyst are main driving factors for
high catalytic activity of SZ-2-600 catalyst. The SZ catalyst was also found to be active for
comparatively less reactive aliphatic terminal and meso-epoxides with amines providing desired
products in excellent yield and selectivity. The SZ catalyst was successfully recycled for six
catalytic cycles without any significant loss in its activity.
Acknowledgements
CSIR-CSMCRI communication no. is DIMC-015-14. The authors are thankful to DST and CSIR
Network Projects on Catalysis for financial support, and also the “Analytical Discipline” of the
Institute for providing instrumentation facilities. Arpan K. Shah and Manish Kumar are also
grateful to AcSIR for Ph. D. registrations and also thankful to K. Sarvanan for his valuable
support.
Captions
18
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Figure 1 Regioselectivity in AoE reaction
Figure 2 (A) PXRD pattern of SZ catalysts prepared in a single step
Figure 2 (B) PXRD pattern of SZ catalysts prepared in two steps
Figure 3 FTIR spectra of selected SZ catalysts
Figure 4 (A) Ammonia-TPD profiles of SZ materials prepared in a single step
Figure 4 (B) Ammonia-TPD profiles of SZ materials prepared in two steps
Figure 5 DRIFT spectra of the catalysts SZ-2-500, SZ-2-600 and SZ-2-700 at 150 oC
Figure 6 Recycling data of AoE catalyzed by SZ-2-600 under optimized reaction condition
Table 1 Crystallite size, Surface area, Pore volume, Average pore diameter and Sulfur value of
all catalysts
Table 2 Acidity measurement of SZ catalysts by NH3-TPD technique
Table 3 Optimization of the catalysts and its loading for AoE reaction under solvent free
condition at room temperature
Table 4 Scope of various substrates for AoE reaction under optimized reaction condition
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22
Page 22 of 38

Table 1 Crystallite size, Surface area, Pore volume, Average pore diameter and Sulfur value of
all catalysts
BET
Total Pore Average Pore
Sulfur
Content
(%)
Sr.
Crystallite
Size (nm)
(%) Wt.
Loss
Material
Surface
Area m2/g
Volume
(cc/g)
Diameter
(nm)
No.
1
2
3
4
5
6
7
8
9
49.3
---
124.5
0.095
3.1
00
0.91
24.9
18.8
8.8
ZrO2
6.94
6.19
3.28
0.78
4.28
3.67
2.55
1.09
SZ-1-120
11.6
9.3
0.204
0.203
0.097
0.167
0.059
0.100
0.164
0.113
31.4
49.7
7.1
---
SZ-1-500
SZ-1-600
SZ-1-700
SZ-2-120
SZ-2-500
SZ-2-600
SZ-2-700
27.3
32.6
---
48.7
45.6
103.4
94.5
79.8
57.5
2.8
10.9
5.0
18.6
11.1
6.2
---
5.4
7.4
7.2
10.5
5.7
3.9
23
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Table 2 Acidity measurement of SZ catalysts by NH3-TPD technique
Sample
Temp (oC) mmol/g
Total
Sample
Temp (oC) mmol/g
Total
524
710
806
0.200
2.971
0.049
87
0.234
0.302
0.091
0.426
0.586
0.013
0.022
0.428
0.445
0.139
0.050
0.355
3.220
357
408
612
102
268
418
615
807
84
1.055
SZ-1-500
SZ-2-500
88
0.242
0.090
0.179
550
714
0.511
0.233
1.495
0.544
SZ-1-600
SZ-1-700
SZ-2-600
SZ-2-700
84
0.074
0.013
0.145
191
330
364
835
24
Page 24 of 38

Table 3 Optimization of the catalysts and its loading for AoE reaction under solvent free
condition at room temperature a
NH2
OH
Catalyst
O
Solvent free
RT
N
H
Sr. No.
Catalyst
ZrO2
Amount (mg)
Time (Min.)
Isolated Yield b (%)
1
2
20
20
20
20
20
20
20
20
20
20
15
25
35
60
60
60
60
30
30
30
30
30
30
30
30
30
75
78
83
85
93
90
87
92
96
90
91
95
87
Zr(OH)4
SZ-1-120
SZ-1-500
SZ-1-600
SZ-1-700
SZ-2-120
SZ-2-500
SZ-2-600
SZ-2-700
SZ-2-600
SZ-2-600
SZ-2-600
3
4
5
6
7
8
9
10
11
12
13
a AoE reaction was carried out using SZ catalyst (amount as mentioned) per 1 mmol of epoxide and
amine under solvent free condition at RT
b Isolated Yield of -amino alcohol
25
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Table 4 Scope of various substrates for AoE reaction under optimized reaction condition a
HO
R
R" NH
R
HN R"
R'
OH
R'
SZ-2-600 (20 mg)
O
R" NH2
Solvent free
RT
R
R'
B
A
Sr.
Time
Isolated Yield
(%) b
Epoxides
Nucleophiles
Product
No.
Min.
OH
1
2
NH2
NH2
30
98
96
O
O
O
N
H
OH
30
N
H
OH
NH2
NH2
NH2
3
4
5
30
1440
60
89
00
90
N
H
OH
O
N
H
OH
O
N
H
OH
O
NH2
6
60
80
N
H
26
Page 26 of 38

OH
NH2
O
O
O
O
7
8
9
60
60
60
90
94
92
N
H
O
OH
O
O
NH2
N
H
OH
NH2
N
H
Cl
Cl
OH
Cl
O
O
Cl
NH2
10
11
60
92
00
N
H
OH
NO2
O2N
NH2
1440
N
H
O
HO HN
NH2
12
13
14
60
60
45
94
81
O
HO HN
NH2
NH2
H
HO
N
O
88
94
OH
H
O
O
N
NH2
NH2
15
16
30
30
OH
3
H
N
93
3
27
Page 27 of 38

OH
O
O
H
N
NH2
NH2
NH2
17
18
19
30
30
30
95
96
91
5
5
7
9
OH
H
N
7
OH
O
O
H
N
9
OH
15
H
N
NH2
NH2
NH2
20
21
22
30
30
30
90
92
89
15
OH
H
N
O
O
O
O
OH
H
N
O
O
OH
OH
H
O
80b
68b
90c
N
Cl
Br
NH2
NH2
NH2
23
24
25
60
120
30
Cl
Br
H
N
O
O
OH
H
N
O
O
O
OH
H
N
O
O
NH2
26
30
98
28
Page 28 of 38

O
O
OH
OH
H
N
O
O
O
NH2
NH2
NH2
27
28
30
30
97
90
Cl
Cl
H
N
O
O
O
O
OH
H
N
O
O
29
30
31
30
90
82c
95
O
OH
H
N
NH2
O
O
180
180
O
O
OH
H
O
O
O
N
NH2
OH
7
7
32
33
34
300
180
68
94
97
O
N
N
H
7
7
O
O
H
N
OH
OH
O
O
O
N
H
N
O
O
N
180
60
O
OH
O
H
NH2
O
O
83c
88
O
N
35
36
O
OH
HN
N
N
N
O
90
O
O
29
Page 29 of 38