Efficient and suitable preparation of N-sulfonyl-1,2,3,4- tetrahydroisoquinolines and ring analogues using recyclable H6P 2W18O62·24H2O/SiO 2 catalyst

Article abstract of DOI:10.1016/j.crci.2012.05.016

Silica gel-supported H₆P₂W₁₈O ₆₂·24H₂O is an efficient and recyclable catalyst for the synthesis of biologically important molecules. Several substituted N-sulfonyl-1,2,3,4-tetrahydroisoquinolines and ring analogues can be prepared in very good yields and purity by direct reaction of N-aralkylsulfonamides and sym-trioxane by a Pictet-Spengler reaction in the presence of a catalytic amount of silica gel-supported H₆P₂W₁₈O ₆₂·24H₂O. Reactions were performed in a low volume of toluene, at 70 °C and for a short time, typically 15 to 30 min. The title heterocyclic compounds were prepared in very good yields (60%-95%) using the described procedure results in a clean and useful alternative, which has the advantages of a greener methodology with operative simplicity, use of a reusable and non-corrosive solid catalyst, soft reaction conditions, low reaction times, and good yields.

Full text of DOI:10.1016/j.crci.2012.05.016

C. R. Chimie 15 (2012) 758–763
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Preliminary communication/Communication
Efficient and suitable preparation of N-sulfonyl-1,2,3,4-
tetrahydroisoquinolines and ring analogues using recyclable
H6P2W18O62Á24H2O/SiO2 catalyst
Gustavo Pasquale a, Diego Ruiz a, Juan Autino a, Graciela Baronetti b, Horacio Thomas c,
Gustavo Romanelli a, ,d
*
a
´
´
´
Catedra de Quımica Organica, Facultad de Ciencias Agrarias y Forestales, Universidad Nacional de La Plata. Calles 60 y 119 s/n, B1904AAN La Plata, Argentina
b Departamento de Ingenierı´a Quı´mica, Facultad de Ingenierı´a, Universidad de Buenos Aires, Ciudad Universitaria, C1428BGA Buenos Aires, Argentina
c
´
Planta Piloto Multiproposito PlaPiMu, UNLP-CICPBA, Camino Centenario y 508, CP1987, Manuel B, Gonnet, Argentina
d
o
´
Centro de Investigacion y Desarrollo en Ciencias Aplicadas ‘‘Dr. Jorge J. Ronco’’ (CINDECA-CCT-CONICET), Universidad Nacional de La Plata. Calle 47 n 257,
B1900AJK La Plata, Argentina
A R T I C L E I N F O
A B S T R A C T
Article history:
Silica gel-supported H6P2W18O62Á24H2O is an efficient and recyclable catalyst for the
synthesis of biologically important molecules. Several substituted N-sulfonyl-1,2,3,4-
tetrahydroisoquinolines and ring analogues can be prepared in very good yields and purity
by direct reaction of N-aralkylsulfonamides and sym-trioxane by a Pictet-Spengler
reaction in the presence of a catalytic amount of silica gel-supported H6P2W18O62Á24H2O.
Reactions were performed in a low volume of toluene, at 70 8C and for a short time,
typically 15 to 30 min. The title heterocyclic compounds were prepared in very good yields
(60%–95%) using the described procedure results in a clean and useful alternative, which
has the advantages of a greener methodology with operative simplicity, use of a reusable
and non-corrosive solid catalyst, soft reaction conditions, low reaction times, and good
yields.
Received 19 April 2012
Accepted after revision 21 May 2012
Available online 27 June 2012
Keywords:
Silica-supported Wells-Dawson catalyst
Pictet-Spengler reaction
N-sulfonyl-1,2,3,4-tetrahydroisoquinolines
and ring analogues
Heterogeneous catalysis
Recyclable catalyst
ß 2012 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
1. Introduction
areas such as medicine and materials science, among
others; in the wide field of structural possibilities that the
Sustainable Chemistry is becoming a wide field in
Chemistry in general and in Organic Synthesis in particu-
lar. Among the 12 principles of Green Chemistry, one of the
main subjects is the use of a green, recoverable and
reusable heterogeneous catalyst [1].
Heteropolyacids (HPA) are well-defined molecular
arrangements with remarkable and useful applications.
Their main technological property is their reusability
because of their solid state and the possibility of generating
heterogeneous catalysis. Diverse electronic and molecular
structures of HPA lead to their application in different
HPA have shown [2], the Wells-Dawson-type primary
structure deserves to be mentioned. It has the formula
-m
[X2M18O62
]
and can be considered as the result of the
fusion of two XM9O34 units, each one with a classic Keggin-
type geometry [3]. Recently, we reported the use of the
Wells-Dawson-structured HPA in the synthesis of diverse
compounds such as flavones [4], coumarins [5], aryl and
aralkyl cinnamates [6], quinoxaline derivatives [7] and
azlactones [8], among others.
Moreover, 1,2,3,4-tetrahydroisoquinolines and deriva-
tives are basic compounds inside many natural alkaloids,
among them ecteinascidin, cherylline and latifine; many
compounds of this type have shown diverse bioactivities
such as anticonvulsant, antimicrobial, antitumor (against
breast and prostatic cancer, and sarcoma), anti-HIV,
* Corresponding author.
E-mail address: gpr@quimica.unlp.edu.ar (G. Romanelli).
1631-0748/$ – see front matter ß 2012 Acade´mie des sciences. Published by Elsevier Masson SAS. All rights reserved.
http://dx.doi.org/10.1016/j.crci.2012.05.016

G. Pasquale et al. / C. R. Chimie 15 (2012) 758–763
759
Scheme 1. Synthesis of N-(3,4-dichlorobenzylsulfonyl)-1,2,3,4-tetrahydroisoquinoline.
antihypertensive, antiarrhythmic, antiherpes, bronchodi-
lator, and as Parkinson disease therapeutic drug, among
others [9–13].
silicagel. All the yields were calculated from crystallized
products. All the products were identified by comparison
of physical data (mp, TLC and NMR) with those reported or
with those of authentic samples prepared by the respective
conventional methods using sulfuric acid as catalyst.
Melting points of the compounds were determined in
sealed capillary tubes and are uncorrected. The 1H-NMR
and 13C-NMR spectra were obtained on a Bruker instru-
ment 400 MHz model as CDCl3 solutions, and the chemical
In particular, N-sulfonyl-1,2,3,4-tetrahydroisoquino-
lines and N-sulfonyl-2,3,4,5-tetrahydro-1H-2-benzaze-
pines are very important precursors for 1,2,3,4-
tetrahydroisoquinoline and 2,3,4,5-tetrahydro-1H-2-ben-
zazepine synthesis, respectively, although they also exist
as substructures of diverse biologically active compounds
[14]. Also, the introduction of sulfur atoms in heterocyclic
compounds is very important since they provide molecules
useful for crop protection [15].
shifts were expressed in
internal standard.
d units with Me4Si (TMS) as the
The classic way for synthesizing these compounds
involves a sulfonylaminomethylation of N-arakylsulfo-
namides [16] using various agents such as s-trioxane in
acid media [17]. Among many of the synthetic strategies
for the formation of an isoquinoline skeleton are
the Pummerer [18], Bischler-Napieralski [19], Friedel-
Craft [20], Horner [21] and Pictet-Spengler reactions
[22–25].
The Pictet-Spengler strategy consists in the formation
of an imino-intermediate from the condensation of an
arylethylamine and a carbonyl compound and then an
intramolecular aromatic electrophilic substitution for
generating the isoquinoline structure. The reaction con-
ditions can be modified in the way that an acyl or sulfonyl
substituent in the nitrogen atom increases the reactivity of
the electrophilic pair, favoring the advance of the reaction.
In this way, many attempts were made modifying the
Pictet-Spengler reaction conditions, including solvent-free
conditions [26], Grignard reagents [27,28], and the use of
diverse types of catalysts as superacids [29], BINOL-
phosphoric acid [30], Preyssler heteropolyacids [31], and
iridium salts [32].
2.1. Preparation of catalyst
H6P2W18O62.24H2O (WD) was synthesized as described
elsewhere [33] from an aqueous solution of
a/b
K6P2W18O62Á10H2O salt. The WD silica-supported catalyst
was obtained by wet impregnation of Grace Davison silica
(Grade 59, specific area = 250 m2/g) with an aqueous
solution of the synthesized WD. A catalyst containing 0.4 g/
g of WD acid was prepared (0.4WDSiO2). Then, samples
were dried at room temperature in a vacuum desiccator for
8 h.
2.2. Catalyst characterization
Bulk and supported catalysts were characterized by 31
P
MASNMR measurements. The 31P MAS-NMR spectra were
recorded in Bruker MSL-300 equipment operating at
frequencies of 121.496 MHz. A sample holder of 5 mm
diameter and 17 mm in height was used. The spin rate was
2.1 kHz, and several hundreds of pulse responses were
collected. Chemical shifts were expressed in parts per
million with respect to 85% H3PO4 as an external standard
for 31P-NMR.
In the present work we describe the preparation and
characterization of the Wells-Dawson-type HPA with
formula H6P2W18O62.24H2O (WD), and the 40% silica
gel-supported analog (WD40); also we present their use as
a recyclable acid catalyst in the synthesis of N-sulfonyl-
1,2,3,4-tetrahydroisoquinolines and ring analogues. For
FTIR spectra were obtained in Nicolet IR.200 equip-
ment. Pellets in BrK and a measuring range of 400 to
4000 cm-1 were used to obtain the FT-IR spectra of the solid
samples at room temperature.
Specific surface areas (SBET) of the catalysts were
determined by nitrogen adsorption/desorption technique
using Micromeritics ASAP 2020 equipment.
The acidic properties of samples were determined by
potentiometric titration using a solution of n-butylamine
in acetonitrile in a Metrohm 794 Basic Titrino apparatus. A
0.05 ml portion of n-butylamine (0.1 N), in acetonitrile,
was added to a known mass of solid (between 0.1 and
0.05 g) using acetonitrile as solvent, and stirred for 3 h.
Later, the suspension was titrated with the same base at
0.05 ml/min. The electrode potential variation was mea-
sured in a Metrohm 794 Basic Titrino apparatus with a
double junction electrode.
example, Scheme
1 shows the synthesis of N-(3,4-
dichlorobenzylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
using this procedure.
2. Experimental
Chemicals were purchased from Aldrich, Fluka and
Merck chemical companies and were freshly used after
purification by standard procedures (distillation and
recrystallization). All the reactions were monitored by
TLC on precoated silica gel plates (254 mm). Flash column
chromatography was performed with 230 to 400 mesh

760
G. Pasquale et al. / C. R. Chimie 15 (2012) 758–763
2.3. Catalytic test
All catalysts were dried overnight prior to use. The
reaction was performed in a round bottom flask, which
was equipped with a condenser and immersed in an oil
bath. In a typical test, N-phenylethyl-3,4-dichlorobenzyl-
sulfonamide (1 mmol) and trioxane (3 mmol) and the bulk
or silica-supported WD acid (1% mmol) in 2 ml toluene
were heated to 70 8C with stirring for the indicated time
(20–30 min). The solvent was evaporated and 10 ml of
toluene was added. The catalyst was filtered and washed
with more toluene.
Thesolutionwas dried overanhydrous Na2SO4. Filtration
and concentration after the recrystallizations of acetone or
ethyl acetate afforded the corresponding pure products.
2.4. Catalyst reuse
Fig. 1. 31P-RMN spectra of WD40.
Stability tests of the bulk or silica-supported WD acid
catalysts were carried out running four consecutive
experiments, under the same reaction conditions. After
each test, the catalyst was separated from the reaction
mixture by filtration, washed with toluene (2 Â 2 ml),
dried under vacuum, and then reused.
N-(3,4-dichlorobenzylsulfonyl)-2,3,4,5-tetrahydro-
1-H-2-benzazepine (2g)
1H-NMR (CDCl3):
d = 1.49 (m, 2H), 3.60 (br t, 1H,
J = 5.1 Hz), 3.84 (s, 2H), 4.45 (br s, 2H), 6.94 (dd, 1H,
J = 8.7 Hz, J = 2.1 Hz), 6.95 (d, 1H, J = 2.1 Hz), 7.19 (br d, 1H,
J = 7.2 Hz), 7.22 (ov m, 1H), 7.25 (ov m, 1H), 7.32 (d, 1H,
J = 8.7 Hz).
2.5. Characterization data of selected compounds
13C-NMR (CDCl3):
d = 28.3, 52.3, 53.1, 58.3, 126.7, 128.6,
N-(4-chlorobenzylsulfonyl)-1,2,3,4-tetrahydroiso-
quinoline (2a)
128.8, 129.2, 129.8, 130.0, 130.4, 132.4, 132.6, 132.9, 137.5,
141.9.
1H-NMR (CDCl3):
d = 2.8 (t, 2H, J = 5.9 Hz), 3.42 (t, 2H,
J = 6.0 Hz), 4.21 (s, 2H), 4.35 (br s, 2H), 6.97 (br d, 1H,
J = 8.7 Hz), 7.10 (br d, 1H, J = 8.7 Hz), 7.17 (ov m, 1H), 7.19
(ov m, 1H), 7.28 (br s, 4H).
3. Results and discussion
3.1. Catalyst characterization
13C-NMR (CDCl3):
d = 29.0, 43.7, 47.3, 56.7, 126.1, 126.5,
The 31P-NMR of Fig. 1 shows the characteristic only
signal at –12.6 ppm of this class of Wells-Dawson structure
[34]. The characteristic bands associated with the Wells-
Dawson structure in the literature are present in the FTIR
spectra of WD shown in Fig. 2: a band due to P–O stretching
at 1091 cmÀ1; two bands attributed to W–O–W at 911 and
778 cmÀ1; and one band at 963 cmÀ1 corresponding to
W = O [33]. The spectra of silica gel-supported acid (WD40)
127.0, 127.4, 129.0, 131.9, 132.0, 133.3, 134.9.
N-(3,4-dichlorobenzylsulfonyl)-7-methoxy-1,2,3,4-
tetrahydroisoquinoline (2c)
1H-NMR (CDCl3):
d = 2.76 (t, 2H, J = 6), 3.47 (t, 2H, J = 6),
4.16 (s, 2H), 4.34 (br s, 2H), 6.49 (d, 1H, J = 2.5 Hz), 6.77 (dd,
1H, J = 8.4 Hz, 2.6 Hz), 7.03 (d, 1H, J = 8.5 Hz), 7.18 (dd, 1H,
J = 8.3 Hz, J = 2.0 Hz), 7.37 (d, 1H, J = 8.2 Hz), 7.40 (d, 1H,
J = 2 Hz).
13C-NMR (CDCl3):
d = 28.0, 44.0, 47.6, 55.3, 56.4, 110.7,
113.6, 125.1, 129.1, 129.9, 130.1, 130.6, 132.4, 132.9, 133.2,
158.2.
N-(3,4-dichlorobenzylsulfonyl)-6,7-dimetoxy-
1,2,3,4-tetrahydroisoquinoline (2d)
1H-NMR (CDCl3):
d = 2.74 (t, 2H, J = 5.9 Hz), 3.48 (t, 2H,
6 Hz), 4.16 (s, 2H), 4.28 (s, 2H), 6.43 (s, 1H), 6.59 (s, 1H),
7.19 (dd, 1H, J = 8.3 Hz, 2 Hz), 7.38 (d, 2H, J = 8.2 Hz).
13C-NMR (CDCl3):
d = 28.4, 43.8, 47.1, 56.5, 56.6, 108.7,
111.7, 123.7, 125.0, 129.1, 129.9, 130.6, 132.4, 132.8, 133.1,
147.9, 148.2.
N-(2-Methoxycarbonylethylsulfonyl)-6-chloro-
1,2,3,4-tetrahidroisoquinoline (2e)
1H-NMR (CDCl3):
d = 2.82 (t, 2H, J = 7.4 Hz), 2.91 (t, 2H,
J = 5.9 Hz), 3.32 (t, 2H, J = 7.4 Hz), 3.57 (t, 2H, J = 5.9 Hz),
4.44 (s, 2H), 7.08 (d, 1H, J = 2.2 Hz), 7.08 (d, 1H, J = 8.1 Hz),
7.17 (dd, 1H, J = 8.2, J = 2.1).
13C-NMR (CDCl3):
126.2, 127.2, 130.4, 131.7, 132.2, 133.6, 170.9.
d = 28.2, 28.5, 43.2, 46.0, 46.7, 52.3,
Fig. 2. FTIR spectra of WD (a) and WD40 (b).

G. Pasquale et al. / C. R. Chimie 15 (2012) 758–763
761
Table 2
Effect of temperature on N-(3,4-dichlorobenzylsulfonyl)-1,2,3,4-tetrahy-
droisoquinoline yields (%).
Entry
Temperature (8C)
Yield (%) WD
Yielda (%) WD40
1
2
3
4
5
25
50
–
38
80
78
–
49
82
77
57
70
90
100
Reaction conditions: N-phenylethyl-3,4-dichlorobenzylsulfonamide,
1 mmol; s-trioxane, 3 mmol; toluene, 2 mL; catalyst, 1% mmol; 30 min;
stirring.
a
Isolated yield.
changes in porosymmetry appear. The comparison with a
bulk acid BET surface value of 1.9 m2/g indicates a big
increase in the specific surface area.
Fig. 3. Potentiometric titration of WD and WD40.
3.2. Catalytic tests
also shown in Fig. 2 exhibit the same bands, with a
widening of the bands attributed to the loss of symmetry
caused by the support media (Fig. 2).
Optimum reaction conditions were examined employ-
ing N-phenylethyl-3,4-dichlorobenzylsulfonamide as test
reaction substrate with s-trioxane in toluene at 70 8C for
2 h. Without the presence of catalyst no reaction was
observed. Similarly, no reaction occurred when the
support (silica gel) was used as catalyst, under the same
reaction conditions. Then the acids WD and WD40 were
tested (Table 2, entry 3) with very good results.First, the
influence of the reaction temperature on the N-(3,4-
dichlorobenzyl-sulfonyl)-1,2,3,4-tetrahydroisoquinoline
synthesis was investigated using both bulk (WD) and
supported catalyst (WD40), and the results are illustrated
in Table 2. In order to obtain the optimal temperature, five
temperatures (25, 50, 70, 90 and 100 8C, Table 2) were
tested.The tested experimental reaction conditions were:
N-phenylethyl-3,4-dichlorobenzylsulfonamide, 1 mmol; s-
trioxane, 3 mmol; toluene, 2 mL; 0.01 mmol catalyst;
30 min. No reaction was observed at 25 8C (entry 1 in
Table 2).
A temperature increase leads to a higher N-(3,4-
dichlorobenzyl-sulfonyl)-1,2,3,4-tetrahydroisoquinoline
yield. For example, the yield of N-(3,4-dichlorobenzylsul-
fonyl)-1,2,3,4-tetrahydroisoquinoline for a reaction time of
30 min at 50 8C was only 38 and 49% (entry 2, Table 2) for
bulk and supported catalysts, respectively, whereas at
70 8C the yields were 80 and 82%, respectively (entry 3,
Table 2). Finally at 100 8C the reaction yields were
considerably lower (57 and 57% respectively entry 5),
due to the several unidentified side products that were
detected by TLC.
To determine the acid properties of bulk and supported
acids we used potentiometric titration (Fig. 3). In order to
interpret the results, it is suggested that the initial
electrode potential (E) indicates the maximum acid
strength of the surface sites, and the values (meq/g solid),
where the plateau is reached, indicate the total number of
acid sites. The acid strength of surface sites can be assigned
according to the following ranges: very strong site,
E > 100 mV; strong site, 0 < E < 100 mV; weak site,
–100 < E < 0 mV; and very weak site, E < –100 mV. The
maximum acid strength of the acid sites for WD is 827 mV.
The magnitude for this value indicates very strong acid
sites for bulk solid acid, very similar to the bulk Keggin
HPA. The values of meq base/g solid where the plateau is
reached indicate three different acid sites. Similarly, the
supported acid shows a low decrease in the maximum acid
strength, 801 mV for WD40. The support (silica) acid
strength was tested, with an initial potential of 25 mV.
When PW is supported on silica, the number of acid sites is
very similar to that of bulk WD (Fig. 3).
The surface area of the supported acid WD40 sample
determined from N2 adsorption–desorption isotherms
using the BET method, BET surface, pore and micropore
volume, and pore diameter are shown in Table 1. All
properties of bulk HPA are lower; in all cases the values are
close to the experimental error of the methods used. This
result shows a reduction of the specific surface area
attributed to particle agglomeration, while no significant
By comparing the conversion values of supported and
bulk catalysts at different temperatures, it was observed
that the difference between them was not as high as
expected considering that the amount of catalyst
employed was always the same and the supported ones
have a well-dispersed active phase. So, these results could
be explained in terms of pseudoliquid behavior of the bulk
catalyst, as we described before. The difference with the
supported catalysts can be explained in terms of diffusion
of reagents and products inside and outside crystallites in
Table 1
Textural parameters.
WD40
Support
BET surface (m2/g)
Pore volume (cm3/g)
Micropore volume (cm3/g)
245.7
1.02
268.41
1.123
0.014
166.82
0.012
˚
Pore diameter (A)
167.28

762
G. Pasquale et al. / C. R. Chimie 15 (2012) 758–763
Table 3
Table 4 displays the effect of the amount of catalyst
(WD40) on the yield of N-(3,4-dichlorobenzylsulfonyl)-
1,2,3,4-tetrahydroisoquinoline in the reaction. The experi-
mental reaction conditions were: N-phenylethyl-3,4-dichlor-
obenzylsulfonamide, 1 mmol; s-trioxane, 3 mmol; toluene,
Effect of time of reaction on N-(3,4-dichlorobenzylsulfonyl)-1,2,3,4-
tetrahydroisoquinoline yields (%).
Entry
Reaction time (min)
Yielda (%) WD
Yielda (%) WD40
1
2
3
4
15
30
45
60
48
80
83
81
70
82
83
82
Table 6
Preparation of N-sulfonyl-1,2,3,4-tetrahydroisoquinolines and ring ana-
logues catalyzed by WD40a.
Reaction conditions: N-phenylethyl-3,4-dichlorobenzylsulfonamide,
1 mmol; trioxane, 3 mmol; toluene, 2 mL; 30 min; 70 8C; stirring.
Entry
1
Product
Yield (%)
33
a
Isolated yield.
Table 4
Effect of amount of catalyst on N-(3,4-dichlorobenzylsulfonyl)-1,2,3,4-
tetrahydroisoquinoline yields (%).
Entry
Catalyst amount (%)
Yielda (%)
1
2
3
4
0.1
1
33
82
82
83
2
2
3
4
83
64
88
5
Reaction conditions: N-phenylethyl-3,4-dichlorobenzylsulfonamide,
1 mmol; trioxane, 3 mmol; toluene, 2 mL; 30 min; 70 8C; stirring.
a
Isolated yield.
the supported catalysts. We assume that the difference in
conversion between bulk and supported catalysts can be
explained considering that they have microporous and
mesoporous structures respectively, with 0.5 and 2.5 nm
pore radius, so the diffusion factor in the whole reaction
has a different influence on both systems, as we have
already reported [35].
For this reason, 70 8C was employed as the ideal
temperature to continue with the analysis of other reaction
variables. Table 3 shows the result for N-(3,4-dichloroben-
zylsulfonyl)-1,2,3,4-tetrahydroisoquinoline synthesis as a
function of reaction time using WD and WD40 catalysts at a
reaction temperature of 70 8C. The experimental reaction
conditions were: N-phenylethyl-3,4-dichlorobenzylsulfo-
namide, 1 mmol; s-trioxane, 3 mmol; toluene, 2 ml; WD40,
0.01 mmol; and 70 8C. It can be observed that the yields of
3,4-dichlorobenzylsulfonyl-1,2,3,4-tetrahydroisoquinoline
increased with the reaction time up to approx. 30 min and
then remained at a constant level.
5
6
59
95
Table 5
Catalyst reuse in N-(3,4-dichlorobenzylsulfonyl)-1,2,3,4-tetrahydroiso-
quinoline yields (%).
7
84
Entry
Cycle
Yielda (%)
1
2
3
4
5
6
0
1
2
3
4
5
82
78
79
77
77
75b
8
80
Reaction conditions: N-phenylethyl-3,4-dichlorobenzylsulfonamide,
1 mmol; trioxane, 3 mmol; toluene, 2 mL; 30 min; 70 8C; stirring.
a
Isolated yield.
aReaction conditions: 1 mmol sulfonamide, 3 mmol trioxane, 2 ml
b
The reaction is not complete in 30 min (conversion 90%) and the
yields of 75% was obtained in a reaction time of 40 min.
toluene, 1 mmol% catalyst, 70 8C, stirring, 30 min.

G. Pasquale et al. / C. R. Chimie 15 (2012) 758–763
763
2 mL mmol; 30 min; 70 8C, and a variable amount of WD40
Acknowledgements
catalyst (0.1%, 1%, 2% and 5%). It can be seen that the yields
increased from 33% to 82% when the amount of WD40
increased from 0.1% to 1% (Table 4, entries 1 and 2). No
relevant changes of reaction yields were observed with
further increase in the amount of WD40 (5%), (83%, Table 4,
entry 4). Thus 1% of WD40 is a suitable amount in this
reaction.
We thank Universidad Nacional de La Plata, CONICET
and ANPCyT for financial support. GB, HT and GR are
members of CONICET.
References
The reusability of the catalysts was investigated in the
sequential reaction of N-phenylethyl-3,4-dichlorobenzyl-
sulfonamide with s-trioxane. At the end of each run the
catalyst was removed, washed with toluene, dried in
vacuum at 40 8C and reused. The results, which are
summarized in Table 5, showed that the catalyst was
reused four consecutive runs and no appreciate loss of its
catalytic activity was observed. Performance of the
reactions under the same conditions using WD40 as a
catalyst showed 78%, 79%, 77%, and 77% of N-(3,4-
dichlorobenzylsulfonyl)-1,2,3,4-tetrahydroisoquinoline
yield, respectively. In the five cycle the conversion of
substrate was 90% and the maximal yields 75% in 40 min.
An additional test was performed in order to evaluate
the possible catalyst solubilization. A WD40 sample was
refluxed in toluene for 2 h, filtered and dried in vacuum till
constant weight. The activity of the so-treated catalyst was
the same as that of the fresh catalyst (81% in 30 min). The
refluxed toluene was used as solvent for attempting the
reaction without adding the catalyst. After 4 h no product
was detected and the starting material was quantitatively
recovered.
Using the optimized conditions, sulphonamide,
1 mmol; s-trioxane, 3 mmol; toluene, 2 mL; WD40,
0.01 mmol; and 70 8C, several N-sulfonyl-1,2,3,4-tetrahy-
droisoquinolines and N-sulfonyl-2,3,4,5-tetrahydro-1H-2-
benzazepines were prepared (Table 6). The yield of the
reaction was comparable for both catalysts. In all the
experiments, the desired products were obtained with
high selectivity. When the sulphonamide and s-trioxane
were treated with the WD40 catalysts for 30 min, the
tetrahydroquinolines and ring analogues were obtained
with very good yields (59%–95%).
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4. Conclusions
The described procedure for the synthesis of N-
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