MCM-41-TBD as a new, efficient, supported heterogeneous catalyst for the synthesis of thioureas

Article abstract of DOI:10.1016/S0040-4039(02)02100-7

The preparation of thioureas, by reaction of carbon disulfide with primary amines, can be efficiently catalyzed, under heterogeneous conditions, by MCM-TBD as a new and reusable catalyst.

Full text of DOI:10.1016/S0040-4039(02)02100-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 8445–8447
MCM-41-TBD as a new, efficient, supported heterogeneous
catalyst for the synthesis of thioureas
Roberto Ballini,a,* Giovanna Bosica,a Dennis Fiorini,a Raimondo Maggi,b,* Paolo Righi,c
Giovanni Sartorib and Raffaella Sartoriob
aDipartimento di Scienze Chimiche dell’Universita`, Via S. Agostino 1, 62032 Camerino (MC), Italy
bDipartimento di Chimica Organica e Industriale dell’Universita`, Parco Area delle Scienze 17A, 43100 Parma, Italy
cDipartimento di Chimica Organica ‘A. Mangini’ dell’Universita`, V. le Risorgimento 4, 40136 Bologna, Italy
Received 11 September 2002; revised 24 September 2002; accepted 25 September 2002
Abstract—The preparation of thioureas, by reaction of carbon disulfide with primary amines, can be efficiently catalyzed, under
heterogeneous conditions, by MCM-TBD as a new and reusable catalyst. © 2002 Elsevier Science Ltd. All rights reserved.
The manufacture of fine chemicals for preparation of
pharmaceuticals, agrochemicals and new materials rep-
resents an ever expanding area of interest. Unfortu-
nately, as clearly stated in recent reviews and reports,
the classical synthetic routes to fine chemicals and
pharmaceuticals are responsible for the production of
large amounts of pollutant by-products.1 This draw-
back can be partly overcome by replacing stoichiomet-
ric processes with cleaner catalytic alternatives.2
Different heterogeneous basic catalysts were thus pre-
pared and utilized to promote fundamental reactions of
synthetic interest such as aldol condensation,7
epoxidation8 and glyceride formation.9 In this context
Jacobs et al. recently reported the preparation of a
novel, heterogeneous and strongly basic catalyst, in
which 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) is cova-
lently bonded to the surface of the mesoporous MCM-
41 silica. This hybrid organic–inorganic material was
claimed to efficiently promote some fundamental base-
catalysed CꢀC forming reactions such as the Knoeve-
nagel condensation and the Michael addition.10
Moreover, a further step toward environmentally
friendly synthetic routes is represented by the applica-
tion of solid and reusable catalysts3 and by the develop-
ment of solventless processes.4
In the course of our continuing investigation on using
heterogeneous catalysts for fine chemicals preparation,
we found that the above hybrid organic–inorganic
material here called MCM-41-TBD efficiently catalyses
the reaction of amines with carbon sulfide affording
N,N%-disubstituted thioureas in good yield and selectiv-
ity. This reaction was examined since, over the last few
years, thiourea moiety has been of interest as a struc-
tural modification to molecules designed as receptor
antagonists, as natural product mimics, or as synthetic
intermediates to amides or guanidines.11 The hybrid
organic–inorganic material MCM-41-TBD was selected
as the base catalyst in the present study being easily
synthesised from commercially available reagents by
using simple experimental methodologies. Here we
show results of a detailed study of the reaction.
The synergic combination of these strategies with the
atom-economy approach opens new important perspec-
tives for the modern development of eco-efficient large-
scale synthetic processes.5
One particular promising area of research which can
combine the advantages of the homogeneous catalysis
with the best properties of the heterogeneous materials
is the immobilization of catalytically active organic
compounds on inorganic solid supports, resulting in the
production of hybrid organic–inorganic catalysts,
which are safely handled and stored and can be easily
recovered by filtration at the end of the reaction and
reused for many cycles.6
Keywords: thioureas; supported bases; heterogeneous catalysis; 1,5,7-
triazabicyclo[4.4.0]dec-5-ene (TBD).
TBD is a strong guanidine base (pKb=25)12 widely
utilised as acid scavenger and homogeneous catalyst,
i.e. for transesterification reactions.
* Corresponding
authors.
Fax:
+39-0737-402297;
e-mail:
roberto.ballini@unicam.it
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02100-7

8446
R. Ballini et al. / Tetrahedron Letters 43 (2002) 8445–8447
The procedure could be efficiently applied to both
aromatic and aliphatic primary amines. Secondary
amines such as, for example, N-methylaniline and
The heterogeneous catalyst MCM-41-TBD was pre-
pared by slightly modifying the methodology
described by Jacobs et al.10 Thus, TBD was previ-
ously linked to 3-trimethoxysilylpropoxymethyloxirane
by nucleophilic addition to the epoxide moiety. The
resulting compound was then anchored to the meso-
porous MCM-41 silica13 by reaction of the
trimethoxysilyl group with the surface silanols. The
loading of the supported TBD was 0.97 mmol/g.
dibutylamine,
were
quantitatively
recovered
unchanged from the final reaction mixture because of
the prevented production of the isothiocyanate inter-
mediate 4. However, when the secondary amine con-
tains an additional primary amino group, the cyclic
thiourea could be obtained in 72% yield (Table 1,
entry i).
In a preliminary experiment the reaction of benzyl-
amine selected as the model reagent with an excess of
CS2 (Scheme 1, R=Bn) was carried out in the pres-
ence of MCM-41-TBD catalyst (molar ratio benzyl-
amine/TBD=10, determined on the basis of loading
value). Thus, a mixture of 1a (3 mmol, 0.32 g), car-
bon disulfide 2 (50 mmol, 3.8 g) utilised as solvent
reagent and MCM-41-TBD (0.3 g) was reacted in a
small autoclave equipped with a magnetic stirring, at
90°C. After 15 h, the thiourea 5a was easily recovered
in 68% yield by removing the excess of CS2 (N2),
dissolving the final product in methanol, removing the
catalyst by filtration, and adding water until the pre-
cipitation was complete (Scheme 1).
Moreover, the use of this heterogeneous catalyst
makes product isolation easier and gives clean reac-
tion.
Finally, we faced the problem of the catalyst recy-
cling: at the end of the model reaction with amine 1a
the MCM-41-TBD was filtered on Bu¨chner funnel,
washed with THF, dried under vacuum and reused.
The catalyst could be utilized with similar results for
two further cycles (reaction: 68%; first recycle: 66%;
second recycle: 63%).
In conclusion, we have reported the use of a solid
base easily prepared by anchoring the guanidine TBD
to mesoporous silica MCM-41 as efficient and
reusable catalyst for the preparation of thioureas
from primary amines and carbon disulfide.
Surprisingly the commercially available cross-linked
polystyrene-bound TBD, commonly utilised as an
acid scavenger, was much less active as basic catalyst
in the same model reaction being 5a obtained in 25%
yield. This result is probably due to the low polarity
of CS2 [ET(30)=32.8 Kcal mol−1]14 which limits the
swelling extent of the material and consequently ham-
pers the access of reactants to the active sites.
Preparation of MCM-41-TBD is as follows: TBD 87.2
mmol,
1
g) was added to
a
solution of 3-
trimethoxysilylpropoxymethyloxirane (5.9 mmol, 1.3
ml) in dry DMF (10 ml) and the stirring was contin-
ued for 15 h at rt. Then, the solution was poured
into a flask containing dry toluene (50 ml) and
MCM-41 previously heated at 300°C for 15 h (3.5 g).
The resulting slurry was refluxed for 1 h and then the
produced methanol was distilled out. This operation
was repeated three times. After cooling, the so pre-
pared supported catalyst was filtered on Bu¨chner and
washed with toluene (100 ml), methylene chloride
(200 ml) and methanol (100 ml) and then treated for
24 h in a Soxhlet apparatus using a 1/1 diethyl ether/
methylene chloride mixture. Finally the solid was
dried under vacuum for 2 h.
General procedure for the preparation of thioureas (3)
is as follow: the selected amine (3 mmol), CS2 (50
mmol, 3.8 g, 3 ml), and MCM-TBD (0.3 g) were
heated in a small autoclave at 90°C. After 15 h the
reaction mixture was cooled to rt, the excess of car-
bon disulfide was then removed by a stream of nitro-
gen, and hot methanol (50 ml) was added in order to
dissolve the crude product, so that the catalyst can be
removed by filtration. After cooling the thiourea was
crystallized by addition of water. The pure product
was isolated by filtration and, when necessary, recrys-
tallised from methanol.
Scheme 1.
Table 1.
Entry
R
5 yield [select.] (%)
a
b
c
d
e
f
g
h
i
PhCH
68 [94]
84 [95]
91 [93]
90 [98]
72 [98]
84 [97]
57 [96]
91 [95]
72 [91]
CH3(CH2)4
CH3(CH2)7
c-C6H11
Ph
4-CH3OC6H4
4-ClC6H4
(R)-Ph(CH3)CH
CH3CH2NH(CH2)2
All the products gave mps and spectral data consis-
tent with the reported ones.

R. Ballini et al. / Tetrahedron Letters 43 (2002) 8445–8447
8447
Acknowledgements
I. Chem. Commun. 1999, 593; (b) Macquarrie, D.; Jack-
son, D. B. J. Chem. Soc., Chem. Commun. 1997, 1781; (c)
Demicheli, G.; Maggi, R.; Mazzacani, A.; Righi, P.;
Sartori, G.; Bigi, F. Tetrahedron Lett. 2001, 42, 2401; (d)
Brunel, D. Micropor. Mesopor. Mater. 1999, 27, 329.
8. Blanc, A. C.; Macquarrie, D. J.; Volle, S.; Renard, G.;
Quinn, C. R.; Brunel, D. Green Chem. 2000, 2, 283.
9. Liu, X.; Chuah, G. K.; Jaenicke, S. J. Mol. Catal. A:
Chem. 1999, 150, 287.
This work was carried out in the framework of the
National Project ‘Stereoselezione in Sintesi Organica.
Metodologie ed Applicazioni’ supported by Ministero
dell’Universita` e della Ricerca Scientifica e Tecnologica,
Rome, Italy and by Fondazione della Cassa di
Risparmio della Provincia di Macerata, Italy. The
authors are grateful to Mr. Pier Antonio Bonaldi
(Lillo) for technical collaboration.
10. Subba Rao, Y. V.; De Vos, D. E.; Jacobs, P. A. Angew.
Chem., Int. Ed. Engl. 1997, 36, 2661.
11. Herr, R. J.; Kuhler, J. L.; Meckler, H.; Opalka, C.
Synthesis 2000, 1569 and references cited therein.
12. Schwesinger, R.; Willaredt, J.; Schlemper, H.; Keller, M.;
Schmitt, D.; Fritz, M. Chem. Ber. 1994, 127, 2435.
13. The mesoporous MCM-41 silica was prepared in our
laboratories by the well-known template synthesis: Beck,
J. S.; Vartuli, J. C.; Roth, W. J.; Leonowicz, M. E.;
Kresge, C. T.; Schmitt, K. D.; Chu, W.; Olson, D. H.;
Sheppard, E. W.; McCullen, S. B.; Higgins, J. B.;
Schlenker, J. L. J. Am. Chem. Soc. 1992, 114, 10834.
14. Reichardt, C. Solvents and Solvent Effects in Organic
Chemistry; VCH: Weinheim, 1988.
References
1. Clark, J. H. Green Chem. 1999, 1, 1.
2. Sheldon, R. Chem. Ind. (London) 1997, 12.
3. Corma, A. Chem. Rev. 1995, 95, 559.
4. Thomas, J. M.; Raja, R.; Sankar, G.; Johnson, B. F. G.;
Lewis, D. W. Chem. Eur. J. 2001, 7, 2973.
5. Trost, B. M. Science 1991, 254, 1471.
6. De Vos, D. E.; Vankelecom, I. F. J.; Jacobs, P. A. Chiral
Catalyst Immobilisation and Recycling; Wiley-VCH:
Weinheim, 2000.
7. (a) Rodriguez, I.; Iborra, S.; Corma, A.; Rey, F.; Jorda`,