Synthesis of new pentacyclo[5.4.0.02,6.03,10.0 5,9]undecane-8,11- dione (PCU) cyanosilylated derivatives using sulphated zirconia and hydrotalcite as catalysts in microwave-assisted reactions under solvent free conditions

Article abstract of DOI:10.3390/molecules16086561

A comparison was made of the effectiveness of the functionalization reactions of pentacyclo[5.4.0.0^2,6.0^3,10.0 ^5,9]undecane-8,11-dione (PCU) using sulphated zirconia in protection-deprotection reactions and Mg/Al hydrotalcite in a cyanosilylation reaction, under classical thermal conditions and imposing microwave radiation; improved yields and reaction times were considered.

Full text of DOI:10.3390/molecules16086561

Molecules 2011, 16, 6561-6576; doi:10.3390/molecules16086561
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
2
,6 3,10 5,9
Synthesis of New Pentacyclo[5.4.0.0 .0 .0 ]undecane-8,11-
dione (PCU) Cyanosilylated Derivatives Using Sulphated
Zirconia and Hydrotalcite as Catalysts in Microwave-Assisted
Reactions under Solvent Free Conditions
1
1
1
Nahí Adriana Guerra-Navarro , Laura Nadxieli Palacios-Grijalva , Deyanira Angeles-Beltrán ,
1
,
2
2
Guillermo E. Negrón-Silva *, Leticia Lomas-Romero , Eduardo González-Zamora ,
3
4
Rubén Gaviño-Ramírez and Juan Navarrete-Bolaños
1
Department of Basic Sciences, UAM-A, Av. San Pablo, No. 180. C.P. 02200, México, D.F.,
Mexico; E-Mails: adnguerra@hotmail.com (N.A.G.-N); nadxielipg@hotmail.com (L.N.P.-G.);
dab@correo.azc.uam.mx (D.A.-B)
2
3
4
Department of Chemistry, UAM-I, San Rafael Atlixco, No. 186. C.P. 09340, México, D.F.,
Mexico; E-Mails: llr@xanum.uam.mx (L.L.-R.); egz@xanum.uam.mx (E.G.-Z.)
Institute of Chemistry, UNAM, Circuito Exterior C.U., C.P.04515, México, D.F., Mexico;
E-Mail: rgaviño@servidor.uam.mx (R.G.-R)
IMP, Eje Central Lázaro Cárdenas No. 152 San Bartolo Atepehuacan, C.P. 07730 México, D.F.,
Mexico; E-Mail: jnavarre@imp.mx (J.N.-B)
*
Author to whom correspondence should be addressed; E-Mail: gns@correo.azc.uam.mx;
Tel.: +52-55-53-18-95-93; Fax: +52-55-53-18-90-00 Ext. 2169.
Received: 10 June 2011; in revised form: 26 July 2011 / Accepted: 29 July 2011 /
Published: 4 August 2011
Abstract: A comparison was made of the effectiveness of the functionalization reactions
2
,6 3,10 5,9
of pentacyclo[5.4.0.0 .0 .0 ]undecane-8,11-dione (PCU) using sulphated zirconia in
protection-deprotection reactions and Mg/Al hydrotalcite in a cyanosilylation reaction,
under classical thermal conditions and imposing microwave radiation; improved yields and
reaction times were considered.
Keywords: sulphated zirconia; hydrotalcite; catalysts; PCU; microwaves

Molecules 2011, 16
. Introduction
6562
1
Organic transformations of polycyclic cage compounds has been the aim of several research groups
since the results of Cookson and coworkers were published in 1958 [1] The synthesis of such
2
,6 3,10 5,9
structures involves functionalization of pentacyclic [5.4.0.0 .0 .0 ] undecane-8,11-dione based on
the protection of one of its reactive centers. This type of reaction is reported using benzene as solvent
and p-toluenesulfonic acid as catalyst to afford the desired product in a 74% yield after a reaction time
of 4 days [2]. Manipulation of protective groups plays an important role in organic chemistry since this
avoids interacting with reactive centers that cannot be involved in certain reactions, so it is necessary
to carry out protection and deprotection reactions with high yields [3].
Various models have been proposed to explain the surface structure and nature of catalytically active
sites in sulphated zirconia (SZ) [4-8], most of which take into account the formation of Lewis as well as
Brønsted acid sites. Formation of Lewis acid sites may be ascribed to the highly covalent character of the
adsorbed sulphates and formation of Brønsted sites result from the interaction of water molecules with
these sulphates [6,9]. Sulphated zirconia is an excellent eco-friendly heterogeneous catalyst in organic
reactions [7,10-12]. Hydrotalcites, a family of anionic clays, are known as layered double hydroxides
(LDH) are an important class of heterogeneous catalysts in organic transformation [13-16]. A salient
feature of as-synthesized or uncalcined Mg/Al hydrotalcite is that they behave as solid Brønsted bases,
the active base sites being mainly structural hydroxyl anions. The base amount estimated by titration using
benzoic acid indicated that samples with different Mg/Al ratios have a small amount of base sites [17]. The
calcination process of the Mg/Al hydrotalcite destroys its structure by removing the interlayer water,
interlayer carbonates and the hydroxyls. The result is an atomic mixture of Mg/Al mixed oxides
phases. The calcination condition is a crucial factor influencing relevant features of the resulting
oxides. The thermal treatment must be at a temperature high enough to decompose the interlayer
anions, but it cannot exceed a critical temperature, at which the phase segregation and sintering effects
take place. Lewis acid sites and Lewis base and Brønsted sites present on the surface of calcined
2 2
hydrotalcites, were determined through pyridine and CO adsorption and microcalorimetry with CO
and benzoic acid [18]. Xie and collaborators determined the basicity of calcined Mg/Al hydrotalcite by
−
the Hammett titration method. Calcined hydrotalcites contain surface Brønsted weakly basic OH
−2
groups, Lewis medium (Mg–O pairs) and strong basic sites related to isolated O anions [19]. It has
been shown that microwave radiation assisted the esterification of free fatty acid, the synthesis of acylals
and anhydro-dimers of o-hydroxybenzaldehydes and regioselective ring opening of oxiranes with
amines using sulphated zirconia as catalyst [20-22].
PCU-like structures have been used as hosts for chiral ammonium ion, as binders in the enantioselective
alkylation of benzaldehyde with diethylzinc [23], in enantioselective Michael reaction [24] and recently in
the synthesis of diamine derivatives, which are potential anti-inflammatory agents used in the treatment
of arthritis rheumatoid [25]. Cyanohydrins are important building blocks for the synthesis of
α-hydroxy acids, α-amino acids, α-hydroxy aldehydes or ketones, β-amino alcohols, and vicinal diols.
Enantioselective cyanosilylation of carbonyl compounds is an effective reaction of nucleophilic
addition in the synthesis of optically active cyanohydrins [26]. Hence, their application would be key
2
,6 3,10 5,9
to functionalization of some structures, in this particular case the pentacyclic [5.4.0.0 .0 .0 ]
undecane-8,11-dione.

Molecules 2011, 16
6563
Most organic synthesis reactions, had only been performed using homogeneous acid or basic
catalysis, however, performing reactions under these conditions has disadvantages in terms of
pollution problems due to the purification processes and the use of solvents during their development.
For such a reason and in order to avoid unwanted situations, in recent years it has been proposed the
use of acid [27] and basic [28] heterogeneous catalysts, which make it possible to reduce the use of
corrosive substances, thus promoting the principles of green chemistry [29].
Microwaves are now widely applied in synthesis processes to reduce reaction times and improve
yields, these two factors together with the use of solid catalysts in solvent-less conditions facilitate
processes like isolation and products purification [30-33].
In this paper we describe the use of solid catalysts with acid and basic properties: Sulphated zirconia
(
[
SZ) and hydrotalcite (HT) respectively, in three types of reactions: (i) Protection of pentacyclic
2
,6 3,10 5,9
5.4.0.0 .0 .0 ] undecane-8,11-dione 1, afforded the respective acetal 2; (ii) The formation of its
protected derivative cyanosilylated 3; and (iii) Subsequent formation of cyanohydrins 4 (Figure 1).
Figure 1. PCU protection, cyanosilylation and deprotection reactions.
O
O
O
NC
NC
O
2
O
O
O
O
O
OH
4
OSi(CH3)3
1
3
2
. Results and Discussion
2
.1. Catalysts Characterization
The X-ray powder (XRD) diffractograms of the sulphated zirconia showed the tetragonal phase
ICSD collection code 066787), as given by reflections in 2θ = 30.18° (with 100 as relative intensity)
and the reflections located at 34.616°, 35.283°, 43.002°, 50.214°, 50.770°, 59.291°, 60.187°, 62.724°,
4.617° and 81.76° [27] (Figure 2).
(
7
Figure 2. Diffractogram of the sulphated zirconia.

Molecules 2011, 16
6564
The isotherm obtained through nitrogen physisorption corresponds to type IV IUPAC [34] (Figure 3),
which shows a narrow hysteresis loop attributed to capillary condensation in the pores according to
2
their mesopores size [35]. The textural properties calculated were: BET surface area (SBET): 90 m /g,
3
the cumulative pore volume (Vp): 0.12 cm /g and the average pore diameter by BJH (Dp): 52.7 Å.
Figure 3. Nitrogen adsorption-desorption plot of sulphated zirconia.
2
θ
Figure 4 shows the diffractogram of the hydrotalcite bearing hexagonal [36-38] symmetry
corresponding to the symmetric wide basal planes (003), (006) and (009), while the non-basal planes
(
102), (105) and (108 ) are asymmetrical.
Figure 4. Diffractogram of HTs.

Molecules 2011, 16
6565
Thermal decomposition of hydrotalcite at 450 °C leads to decomposition of carbonate and
dehydroxylation, obtaining the mixed oxide Mg(Al)O, with a structure similar to that of MgO,
periclase-type [38]. In the periclase phase, the peaks observed correspond to (200) and (220) planes,
with angles centered at 2θ = 43° and 62°, respectively (Figure 5).
Figure 5. Diffractogram of HTc.
Textural properties of the hydrotalcites prepared are summarized in Table 1. After thermal
decomposition by calcination the porosity increases substantially generating a more pronounced
hysteresis loop in the isotherm of the calcined hydrotalcite (HTc), indicating the presence of
mesoporosity. The adsorption-desorption isotherms of N
2
of the hydrotalcites are shown in Figures 6 and
7
and corresponds to Type II IUPAC, and a hysteresis loop type H3 under the same classification.
Table 1. Hydrotalcites’ textural properties.
2
Catalyst Surface area (SBET) (m /g) Pore Volume (cc/g) Pore diameter (Å)
Hts
Htc
66.62
241.21
0.44
0.74
266.88
159.70
The thermal stability of the as-synthesized and calcined hydrotalcite were evaluated by TGA
experiments. Two mayor weight loss peaks are observed in Figure 8. The first peak (near 177 °C) has
been asociated with elimination of physically adsorbed water as well as water molecules in the
interlamellar region 11.63%. The second weight loss peak (around 364 °C) was due to removal of
interlayer anions and the deshydroxylation of layer hydroxyl groups 26.29% [39]. Sulphated zirconia
losses only 1% of weight due to water before 100 °C and then 10% after 600 °C due to sulphate
species decomposition (Figure 9). The basic character of as-synthezised and calcined hydrotalcites
2 2
were compared by CO adsorption FT-IR experiments. CO was adsorbed on a sample of

Molecules 2011, 16
6566
as-synthezised hydrotalcite, then desorbed at 5, 20, 50, 100, 200, 300, 400, and 450 °C and did not
show temperature dependence. On the other hand, the calcined hydrotalcite displayed a decrease of the
CO desorbed quantity as a function of increasing temperature. Deconvolution analysis of FT-IR
2
−1
spectra in the region of 1200–1800 cm showed that the calcined hydrotalcite basic catalytic activity
is due to the CO interaction with basic sites with aprotic character on the structure of the solid
2
material. This is explained by the absence of the bicarbonate band.
Figure 6. Nitrogen adsorption-desorption plot of HTs.
Figure 7. Nitrogen adsorption-desorption plot of HTc.

Molecules 2011, 16
6567
Figure 8. TGA and DTA profiles of HTs.
100
0.14
0
0
0
0
0
0
.12
.10
.08
.06
.04
.02
9
8
7
6
0
0
0
0
0.00
1000
0
200
400
600
800
Universal V4.5A TA Instruments
Temperature (°C)
Figure 9. TGA and DTA profiles of sulphated zirconia.
1
00
0.10
0.08
0.06
0.04
0.02
9
9
8
8
7
5
0
5
0
5
0.00
1000
0
200
400
600
800
Universal V3.9A TA Instruments
Temperature (°C)

Molecules 2011, 16
6568
Figures 10 and 11 correspond to deconvolution analysis of the carbonates region for both hydrotalcites;
the plots demonstrate a variation on the distribution of the carbonate species on as-synthezised and
calcined samples; as-synthezised hydrotalcite had 37% of monodentate carbonates and 62% bidentate
species. The calcined showed 26% of monodentate carbonates and 74% of bidentated [40].
Figure 10. Deconvolution plot of the carbonates zone FT-IR spectra of as-synthezised hydrotalcite.
-
1
1
1
1
1
1
1
7
6
5
4
3
2
1
.0x10
-
.0x10
-
.0x10
-
.0x10
-
.0x10
-
.0x10
-
.0x10
0.0
-
1
-1.0x10
1200
1300
1400
1500
1600
1700
1800
−1
Wave number (cm )
Figure 11. Deconvolution plot of carbonates zone FT-IR spectra of calcined hydrotalcite.
-
1
1
1
1
1
5
4
3
2
1
.0x10
-
.0x10
-
.0x10
-
.0x10
-
.0x10
0.0
-1
-1.0x10
1200
1300
1400
1500
1600
1700
1800
−1
Wave number (cm )

Molecules 2011, 16
.2. Catalytic Activity
Microwave irradiation-assisted pentacyclo [5.4.0.0 .0 .0 ] (PCU) 1 transformation coupled with
6569
2
2
,6 3,10 5,9
solvent-less reaction medium conditions, in the presence of heterogeneous catalysts (sulfated zirconia
and calcined hydrotalcite Mg/Al) were used to enhance reaction rates and to simplify work-up,
particularly purification. The preparation of octahydrospiro[2,4,1(epiethane[1,1,2]triyl)cyclobuta
[
cd]pentalene-5,2'-[1,3]dioxolan]-7-one (2), a typical acid-catalyzed reaction, could be conducted
successfully with very good yield (99%) in only five minutes. In classic thermal conditions, at 80 °C
using toluene as solvent, the reaction time was 45 minutes, Scheme 1.
Scheme 1. Protection reaction.
HOCH CH OH
2
2
2
-
ZrO /SO4
2
Under solvent free
a) Classic conditions
b) Microwaves
O
O
O
O
O
1
2
A simple and convenient method for the addition of TMSCN to protect the PCU compound 2 is also
described. Calcined hydrotalcite Mg/Al under solvent-free conditions at 0 °C and microwave-assisted
is found to possess a strong basic property to transform 2 smoothly into the corresponding
7-hydroxyoctahydrospiro[2,4,1-(epiethane[1,1,2]triyl)cyclobuta[cd]pentalene-5,2'-[1,3]dioxolane]-7-
carbonitrile 3 in high yields (94% in 1.5 h). In classic thermal conditions at 0 °C, the reaction time was
5
h with 98% yield, Scheme 2.
Scheme 2. Cyanosilylation reaction.
Hydrotalcite
CNTMS
Under solvent free
a) Classic conditions
b) Microwaves
O
O
O
2
NC
O
O
OSi(CH3)3
3
Sulphated zirconia is found to be a highly efficient heterogeneous solid catalyst in the activation
reaction of trimethylsilyl cyanide (TMSCN) to facilitate aldehyde cyanosilylation. The sulphated
zirconia is a chemoselective catalyst for the cyanosilylation reaction of aldehydes [41], while
hydrotalcites catalyze both aldehydes and ketones [42].
The microwave-assisted deprotection reaction of cyanosilylated compound 3 was carried out in
acetonitrile solvent using sulphated zirconia as catalyst, giving 7-((trimethylsilyl)oxy)octahydrospiro
[2,4,1-(epiethane[1,1,2]triyl)cyclobuta[cd]pentalene-5,2'-[1,3]dioxolane]-7-carbonitrile, Scheme 3.

Molecules 2011, 16
6570
Scheme 3. Deprotection reaction.
ZrO /SO4-2, CH CN
2
3
a) Classic conditions
b) Microwaves
O
O
NC
NC
O
3
O
OSi(CH3)
OH
4
3
Table 2 summarizes the optimal reaction times and yields of each product obtained from protection-
2,6 3,10 5,9
cyanosilylation-deprotection reactions of pentacyclic [5.4.0.0 .0 .0 ]undecane-8,11-dione.
Table 2. Catalytic activity results.
Substrate
Time(h)
Product
Yield (%)
a
a
0
.75
99.8
b
O
b
0
.083
99.7
O
O
O
2
O
1
c
c
5
.00
88.8
O
d
O
d
1
.30
NC
94.1
O
2
O
O
)
3 3
OSi(CH
3
e
f
e
6
.00
90.1
O
O
f
NC
91.7
NC
0.33
O
O
OSi(CH
3
)
3
OH
4
3
Reaction conditions: (a) PCU (1.15 mmol), ethylene glycol (1.15 mmol), toluene (1 mL),
−
2
−2
ZrO /SO (25 mg), 80 °C; (b) PCU (1 mmol), ethylene glycol (1 mL), solventless, ZrO /SO
4
(
2
4
2
2,6 3,1
5,9
25 mg), 150 °C, 290 Watts; (c) Pentacyclic [5.4.0.0 .0 0.0 ]undecane-8,11-dione monoethylene-
acetal (2 mmol), TMSCN (2 mmol), solventless, calcined hydrotalcite (25 mg), 0 °C;
2
,6 3,1
5,9
(
d) Pentacyclic [5.4.0.0 .0 0.0 ] undecane-8,11-dione monoethylene-acetal (2 mmol), TMSCN
(
[
(
2 mmol), solventless, calcined hydrotalcite (25 mg), 0 °C, 290 Watts; (e) Pentacyclic
2
,6 3,1
5,9
5.4.0.0 .0 0.0 ]undecane-8,11-dione monoethylene-acetal cyanosilylated (1 mmol), acetonitrile
−2
2,6 3,1
5,9
1 mL), ZrO /SO4
(25 mg), 60 °C; Pentacyclic [5.4.0.0 .0 0.0 ]undecane-8,11-dione
2
−
2
monoethylene-acetal cyanosilylated (1 mmol), acetonitrile (1 mL), ZrO /SO
(25 mg), were
2
4
irradiated at 60 °C, 20 min, 100 Watts.
Under the reaction conditions described above, in each case the conversion of the starting material
is close to 100%, with the selective formation of products labeled in (Figure 1) as 2, 3 and 4
respectively, which implies a high efficiency of the reaction procedure thus described, to obtain the

Molecules 2011, 16
6571
2
,6 3,1
5,9
cyanohydrin derived from the pentacyclic [5.4.0.0 .0 0.0 ]undecane-8,11-dione (PCU). As can be
seen through comparison of the yields obtained by conventionally heated methods, the use of
microwaves in the case of protective reactions of the PCU, gave yields that were almost the same,
although with the use of microwave reaction only the time improves, whereas for subsequent reactions,
from cyanosilylation and deprotection, the use of microwave radiation improves both the yields and
reaction times.
The combined merits of microwave irradiation solvent free condition and solid catalysts make the
organic transformation a safe operation, reducing pollution to low levels, giving rapid access to
products and simplifying workup. The solid catalysts sulphated zirconia and calcined hydrotalcite
Mg/Al can be recovered by centrifugation, reactivated through thermal treatment and reused in at least
five reaction cycles.
3. Experimental
3.1. General
Sulphated zirconia synthesis. Zirconium n-propoxide (20 mL, 70% n-propanol) was mixed with
2
3
-propanol (30 mL) and stirred with a magnetic bar. Then, an acid solution (1 mL 98% sulfuric acid in
.2 mL distilled water) was added dropwise in order to hydrolyze the zirconium n-propoxide to obtain
the gel. The solid was filtered and dried at 80 °C until complete alcohol evaporation, then calcined in
air at 600 °C for 6 h [43].
Hydrotalcite synthesis. A solution of NaOH (0.35 mol) and Na CO (0.093 mol) in 100 mL of
2
3
3 2 3 3 2
deionized water was added to a solution of Mg(NO )·6 H O (0.1 mol) and Al(NO ) ·9H O (0.05 mol)
in 70 mL of deionized water. The addition was made dropwise over 4 h, thus forming a white gel
which is then stirred and heated to 60 °C for 18 h. The resulting gel was allowed to cool and washed
2
with deionized H O to pH = 7. The compound was dried at 100 °C overnight, thereby obtaining the dry
hydrotalcite (HTs). The calcined hydrotalcite (HTc) was obtained by heating 2 g of HTs 10 °C/min to
4
50 °C in a tubular furnace (Thermolyne 21100) under air flow for 8 h [28].
Powder X ray diffraction (XRD) was performed with a Philips X’Pert Instrument using Cu-Kα
radiation (45 kV, 40 mA). Nitrogen adsorption/desorption isotherms were obtained at −196 °C on
Micromeritics ASAP 2020 equipment. The reaction products were analyzed by GC-FID (Agilent
Technologies 6890N) equipped with a HP-5 column with the program 70–180 °C (20 °C /min) for
6.50 min then 180–280 °C (15 °C/min) for 7 min, injector 250 °C, detector 280 °C. Mass spectra were
obtained by GC-MS (Agilent Technologies 6890N, Detector 5973) using methane chemical ionization.
1
13
H-NMR and C-NMR spectra were measured at 500 MHz and 125 MHz, respectively, with the aid of
a Bruker Avance-III DMX-500 spectrometer, using CDCl as solvent and tetramethylsilane as internal
standard. FT-IR spectra were recorded also with a Bruker Vector 33 ATR spectrometer. All reagents
3
1
13
and solvents were purchased from Aldrich. All products were identified by IR, H-NMR, C-NMR,
mass spectra and by comparison of their corresponding melting points. The hydrotalcites’ basicity was
measured using FT-IR with CO
2
(research grade) as probe molecule. Measurements were performed
using a Nicolet Magna IR 560 spectrometer equipped with a Harrick ATC Prayin Mantis accessory.

Molecules 2011, 16
6572
The as synthesized and calcined hydrotalcite samples were treated from room temperature to 500 °C
under nitrogen atmosphere (20 mL/min) then cooled, CO was introduced to the chamber during 1 h
2
(20 mL/min) and finally, the temperature was increased to 500 °C while the FT-IR spectra were
recorded. TGA and DTA analysis of hydrotalcites were made using a TA SDT Q600 equipment.
A 10 °C/min ramp under nitrogen was used from room temperature to 1000 °C.
3
.2. Procedure for the PCU Protection
Conventional heating method. In a closed system were placed PCU (1, 1.15 mmol), ethylene glycol
1.15 mmol) and toluene as solvent (1 mL) in the presence of sulphated zirconia (25 mg). The reaction
(
mixture was stirred for 45 min at 80 °C, the sulphated zirconia was recovered by filtration and washed
with CH Cl . The filtrate was dried with anhydrous sodium sulfate and evaporated to dryness,
2
2
2
,6 3,10 5,9
obtaining the corresponding pentacyclic [5.4.0.0 .0 .0 ]undecane-8,11-dione monoethylene acetal
(yield 99.8%).
2
Microwave assisted method. In a closed system were placed: PCU (1, 1.0 mmol) and ethylene glycol
1 mL) without solvent, and with sulphated zirconia (25 mg). The reaction mixture was placed in a
(
CEM Discover Labmate® reactor at 150 °C and 290 W for 5 min with rapid stirring. Subsequently, the
reaction crude was filtered, evaporated to dryness and purified on a chromatographic column to give
2
,6 3,10 5,9
selectively the corresponding pentacyclic [5.4.0.0 .0 .0 ]undecane-8,11-dione monoethylene
acetal 2 (yield 99.7%).
Octahydrospiro[2,4,1-(epiethane[1,1,2]triyl)cyclobuta[cd]pentalene-5,2'-[1,3]dioxolan]-7-one
(2).
White solid (yield 99.7%); m.p. 69–70 °C. (m.p. lit. 73–73.5 °C [28]); GC-MS for C13 (218 g/mol):
14 3
H O
+
+
+
−1
[
M+1] = 219, [M+29] = 247 y [M+41] = 259; FTIR-ATR (cm ): 2979, 1742, 1340, 1121, 1094,
1
1
2
039; H-NMR (500 MHz; CDl
3
): δ (ppm) 3.98–3.91 (m, 3H), 3.90–3.84 (m, 1H), 2.99–2.95 (m, 1H),
.85–2.80 (m, 2H), 2.66 (dddd, J = 8.2, 6.6, 3.0, 1.4 Hz, 1H), 2.62 (ddq, J = 5.4, 4.1, 1.4 Hz, 1H), 2.57
(
dddd, J = 8.4, 6.2, 2.3, 1.1 Hz, 1H), 2.52–2.49 (m, 1H), 2.44 (ddt, J = 10.0, 4.1, 2.0 Hz, 1H), 1.88 (dt,
1
3
3
J = 11.0, 1.5 Hz, 1H), 1.59 (dt, J = 11.0, 1.5 Hz, 1H); C-NMR (125 MHz; CDl ): δ (ppm) 215.02,
1
13.79, 65.58, 64.38, 52.89, 50.61, 45.72, 42.75, 42.17, 41.36, 41.21, 38.60, 36.22.
2
,6 3,10 5,9
3
.3. Procedure for the Cyanosilylation of Pentacyclic [5.4.0.0 .0 .0 ]undecane-8,11-dione Mono-
ethylene Acetal (2)
Conventional heating method. In
a
closed system, there were placed pentacyclic
2
,6 3,10 5,9
[5.4.0.0 .0 .0 ]undecane-8,11-dione monoethylene acetal (2, 1.0 mmol) and TMSCN (2.0 mmol)
without solvent, and calcined hydrotalcite (25 mg) and the reaction mixture was stirred for 5 h.
Subsequently, the catalyst was removed by filtration and the liquid obtained was evaporated to dryness
and purified on a chromatographic column to give selectively the desired new cyanohydrin 3
(yield 88.8%).
Microwave-assisted method. In
a
closed system there were placed pentacyclic
5.4.0.0 .0 .0 ]undecane-8,11-dione monoethylene acetal (2, 0.5 mmol) and TMSCN (1.0 mmol)
without solvent, and calcined hydrotalcite (25 mg) and the reaction mixture was placed in a CEM
2
,6 3,10 5,9
[

Molecules 2011, 16
6573
Discover Labmate® microwave reactor at 0 °C and 290 W, with rapid stirring for 1.5 h. Subsequently,
the catalyst was removed by filtration and the liquid obtained was evaporated to dryness and purified
on a chromatographic column to give selectively the desired cyanohydrin 3 (yield 94.1%).
(
(7-Isocyanooctahydrospiro[2,4,1-(epiethane[1,1,2]triyl)cyclobuta[cd]pentalene5,2'[1,3]dioxolan]-7-
yl)oxy)trimethylsilane (3). Yellow solid (yield 94.1%). m.p. 94–95 °C; GC-MS for C H NO Si;
1
7
23
3
+
+
+
−1
(
317 g/mol): [M+1] = 318, [M+29] = 346, [M−CN] = 291; FTIR-ATR (cm ): 2955, 2240, 1307,
1
1
251, 1102, 880, 838, 782; FAB-MS m/z (rel. int.%): obs. 317.1422 (55.2) cal. 317.1447; H-NMR
(CDCl
3
, 500 MHz): δ (ppm) 3.94–3.91 (m, 2H), 3.83–3.79 (m, 1H), 3.74 (ddd, J = 7.6, 6.7, 6.4 Hz,
1
2
H), 3.02–2.99 (m, 1H), 2.83 (tq, J = 4.7, 1.6 Hz, 1H), 2.71–2.65 (m, 4H), 2.50–2.46 (m, 1H),
13
.23–2.20 (m, 1H), 1.70 (d, J = 11.1 Hz, 1H), 1.25 (dt, J = 11.0, 1.7 Hz, 1H), 0.24 (s, 9H); C-NMR
): δ (ppm) 123.10, 114.40, 75.15, 65.96, 62.42, 51.56, 47.42, 44.96, 44.75, 43.91,
9.79, 39.59, 38.60, 34.46, 0.86.
(125 MHz; CDl
3
3
2
,6 3,1
5,9
3
.4. Deprotection Procedure for the Pentacyclic [5.4.0.0 .0 0.0 ]undecane-8,11-dione Mono-
ethylene Acetal Cyanosilylated 3
Conventional heating method. In a closed system the cyanohydron of the pentacyclic
[5.4.0.02,6.03,10.05,9] undecane-8,11-dione monoethylene acetal (1.0 mmol) and acetonitrile (1.0 mL)
were placed with sulphated zirconia (25 mg). The reaction mixture was stirred for 6 h at 60 °C.
Subsequently, the catalyst was filtered selectively obtaining the desired new product 4 (yield 90.1%).
Microwave-assisted. In a closed system, there were placed the product cyanohydrin of the pentacyclic
[
5.4.0.02,6.03,10.05,9]undecane-8,11-dione monoethylene acetal 3 (1.0 mmol) and acetonitrile (1.0
mL) in the presence of sulphated zirconia (25 mg). The reaction mixture was stirred in a CEM
Discover Labmate® microwave reactor at 60 °C and 100 W for 20 min, with rapid stirring. Subsequently
the catalyst was filtered selectively obtaining the desired new product 4 (yield 91.7%).
7
-Isocyanooctahydrospiro[2,4,1-(epiethane[1,1,2]triyl)cyclobuta[cd]pentalene-5,2'-[1,3]dioxolan]-7-
+
+
3
ol (4). Yellow oil. GC-MS for C14H15NO (m.w.: 245 g/mol): [M+1] = 246, [M+29] = 274,
+
−1
[M+41] = 286; FTIR-ATR (cm ): 3433, 2974, 2871, 2247, 1342, 1275, 1212, 1143, 1036, 904, 868,
1
644; FAB-MS m/z (rel. int.%): Obs. 245.0989 (66.3) calc. 245.1052; H-NMR (500 MHz, CDCl
3
):
δ (ppm), 3.82–3.80 (m, 2H), 3.78–3.75 (m, 2H), 3.26–3.22 (m, 1H), 3.21–3.17 (m, 1H), 2.87–2.79 (m,
H), 2.75–2.72 (m, 1H), 2.64–2.61 (m, 1H), 2.13–2.11 (m, 1H), 1.99 (dt, J = 10.9, 1.5 Hz, 1H), 1.64
4
1
3
(
dt, J = 11.0, 1.6 Hz, 1H); C-NMR (125 MHz, CDCl ): δ (ppm) 122.63, 117.96, 78.44, 68.15, 61.94,
3
6
0.63, 53.70, 50.83, 45.38, 43.58, 43.38, 42,76, 42.23, 41.25.
4
. Conclusions
We have demonstrated that the use of sulphated zirconia and hydrotalcites Mg/Al, provides efficient
results in the organic transformations as protection, cyanosililation and deprotection of the pentacyclo
2
,6 3,10 5,9
[
5.4.0.0 .0 .0 ]undecane-8,11-dione, under soft treatment and in the absence of solvents.
Microwave-assisted method improves the performances that are obtained under thermal classic
conditions and diminishing the reaction times.

Molecules 2011, 16
6574
Acknowledgements
NAGN thanks CONACYT for her studentship 142058 to pursue her Ph.D. degree in Materials
Science and Engineering, for the support granted through project no. 59417. DAB, GNS, LLR, EGZ,
RGR and JNB wish to acknowledge the SNI for the distinction of their membership and the stipend
received.
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2011 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article
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(