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Microwave enhanced synthesis of N-propargyl derivatives of imidazole
Applied Surface Science 252 (2006) 6067–6070 www.elsevier.com/locate/apsusc
Microwave enhanced synthesis of N-propargyl derivatives of imidazole A green approach for the preparation of fungicidal compounds Elizabeth Perozo-Rondo´n a, Laureano Costarrosa a, Rosa M. Martı´n-Aranda a,*, Marı´a L. Rojas-Cervantes a, Miguel A. Vicente-Rodrı´guez b a
Departamento de Quı´mica Inorga´nica y Quı´mica Te´cnica, Facultad de Ciencias, UNED, Paseo Senda del Rey no. 9, Madrid 28.040, Spain b Departamento de Quı´mica Inorga´nica, Universidad de Salamanca, Plaza de la Merced s/n, E-37008 Salamanca, Spain Available online 7 December 2005
Abstract N-Propargyl imidazole has been synthesized by Knoevenagel condensation of benzaldehyde with propargyl bromide, assisted by microwave irradiation. Two alkaline-promoted clays (Li+- and Cs+-exchanged saponites) have been used as catalysts. The influence of several factors, such as irradiation power, irradiation time and alkaline promoter has been studied. The catalysts were characterized by XRD and chemical analysis. The basicity enhancement is directly connected to the presence of alkaline metal promoters in the saponite structure. In addition, a significant increase in the conversion values has been found when the reaction is activated by microwave irradiation, as compared with thermal activation. The yield to the N-propargyl imidazole shows a maximum for the Cs+-saponite at 750 W in only 5 min of microwave irradiation. This green and solvent-free procedure can be extended to the preparation of other N-substituted heterocycles, which could serve as precursors in the primary route to pharmaceutical compounds of interest. # 2005 Elsevier B.V. All rights reserved. PACS: 82.65.J Keywords: Basic clays; Microwave irradiation; Propargylation; Imidazole
1. Introduction The development of solid base catalysts for fine chemicals production is nowadays a subject of increasing interest [1,2]. Hydrotalcites [3], zeolites [4] and sepiolites [5], among others have shown interesting behavior as base catalysts. Moreover, new technologies are being employed to accelerate such catalytic reactions under mild conditions. Microwave irradiation is an alternative heating system to conventional heating methods, which affords interesting reactivity under mild conditions and very short reaction times [6,7]. In general, the anionic alkylation of heterocycles is the primary route to produce important fungicidal and anticonvulsant compounds [8]. N-Propargyl heterocycles of type A (Scheme 1) are of interest due to their pharmacological
* Corresponding author. Tel.: +34 1 3987351; fax: +34 1 3986697. E-mail address: [email protected] (R.M. Martı´n-Aranda). 0169-4332/$ – see front matter # 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.apsusc.2005.11.005
applications, but usually, in basic media the reaction between the N-heterocycles and propargyl bromide affords a mixture of N-allyl (B) and N-propargyl (C) derivatives [9]. In the present study, we investigate the effect of the microwave heating on the activity and selectivity of two basic clays in the alkylation of imidazole with propargyl bromide. Clays are known, in microwave terminology as ‘‘lossy’’ materials, which means that they are efficient absorbers of microwave radiation converting it into heat. This allows a reduction of the reaction temperature values and increases the selectivity towards the N-propargyl derivative. 2. Experimental 2.1. Preparation and characterization of alkaline-doped saponites The starting material used in this work is a natural saponite from Yunclillos deposit (province of Toledo, Spain), supplied
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The yield is expressed in terms of the amount of A obtained in wt.%. 2.3. General procedure for conventional heated reactions
Scheme 1. Alkylation of imidazole with propargyl bromide.
by TOLSA, S.A. The 2 mm fraction of the clay was obtained by careful aqueous decantation of the raw material. The chemical weight percent composition of this clay is SiO2: 49.45; Al2O3: 4.72; Fe2O3: 1.29; MgO: 24.34; TiO2: 0.20; MnO: 0.03; CaO: 0.78; Na2O: 0.07; K2O: 0.44 and the loss by ignition is 18.31 wt.%. X-ray diffraction shows that this fraction contains small amounts of sepiolite and quartz. Considering these impurities, the structural formula of saponite, on the basis of 22 oxygen atoms, was found to be: (Si7.42Al0.58) O20 (Mg5.16Fe0.14Al0.26Mn0.004Ti0.02) (OH)4 [Mg0.24Ca0.124Na0.020K0.084]. The cation exchange capacity (CEC) of this sample was 115 meq/100 g of dry clay, and the BET surface was 161 m2/g. Li+-saponite (Li+-SA) and Cs+-saponite (Cs+-SA) were prepared by a two-step synthetic process. First, homoionic Na+-saponite (Na+-SA) was obtained by washing 30 g of saponite (2 mm fraction) three times with 500 mL of 1 M NaCl solution. In the second step, Li+- and Cs+-exchanged solids were prepared by treating the sodium clay with solutions of the corresponding chlorides. 1.4 g of LiCl or 2.6 g of CsCl were added to a suspension containing 10 g of Na+-SA in 500 mL of water. These suspensions were stirred for 24 h and then washed with water until no chloride anions were detected. The composition of the clays was determined by atomic absorption (AA) on a Perkin-Elmer 4100 ZL spectrometer. Crystalline structures of the samples were analyzed by X-ray diffraction (XRD) with a Siemens Krystalloflex D500 diffractometer, using filtered Cu Ka radiation. The basicity of the Li+-SA and Cs+-SA samples was previously evaluated by the Knoevenagel condensation probe reaction, described by Corma and Martı´n-Aranda [5], which has been applied to estimate the basicity of a wide range of microporous solid materials [1,10]. 2.2. General procedure for microwave irradiated reactions Imidazole (4 mmol) and the corresponding clay catalyst (0.1 g) were blended in a Teflon vessel and propargyl bromide (4.5 mmol) was added. The mixture was irradiated in a microwave oven (Sanyo EM881) at different powers (300 and 750 W). The temperature was measured at the end of each run. After cooling, the reaction products were extracted with acetone and filtered. The reaction was followed by gas chromatography in a Konik KNK-3000-HRGC system with a 60 m long BP1 capillary column. The mass spectra were obtained on a Hewlett-Packard HP5871-A spectrometer.
Imidazole (4 mmol) and the catalyst (0.1 g) were mixed in a Pyrex flask and then, propargyl bromide (4.5 mmol) was added. The mixture was heated (in absence of any solvent) up to the reaction temperature. The samples were taken periodically from 15 to 60 min, extracted with acetone, and filtered. The reaction evolution was followed by gas chromatography. 3. Results and discussion 3.1. Characterization of alkaline-doped saponites Li+-SA fixes 0.12 wt.% of Li+ (referred to the dehydrated sample) indicating that 0.138 exchangeable positions are occupied by this cation in the structural formula given above. Cs+-SA fixes 0.97 wt.% of Cs+, equivalent to 0.058 positions in the structural formula given above. This means that under the above experimental conditions about 16% of the exchangeable positions of the clay were effectively exchanged by Li+ and only about 7% by Cs+, the rest of the positions remained occupied by Na+ cations. Although, in both cases, Li+ and Cs+ cations were in excess with respect to the CEC of the clay in the exchanging solution, a high degree of substitution is not expected when exchanging only once with these cations. Higher substitution degrees may be reached by repeating the exchanging processes, but the amounts of Li+ and Cs+ incorporated to the clays were considered acceptable for the purpose of the study (the effect of microwave activation combined with a mild basicity of the catalyst). The X-ray diffraction patterns of the exchanged solids are displayed in Fig. 1. They show the usual patterns of wellordered saponites. The intensity of Na+-SA diffractogram, included for comparison, is very similar to that of the <2 mm fraction of the natural clay, and compared with them, Li+-SA has a more intense (0 0 1) reflection peak, whereas the Cs+SA has a less intense and wider reflection. Thus, the exchanging with Li+ produces a increased ordering of the layers, while the exchanging with Cs+ has an opposite effect. At the same time, the basal spacing of the Na+-SA and Cs+˚ , whereas for the Li+-SA this spacing is SA is close to 12.5 A ˚ , the same as for the natural clay, which close to 14.7 A mainly has alkaline-earth cations in exchangeable positions (see the structural formula given above). The basal spacings agree with the presence of a monolayer (Na+-SA and Cs+SA) or a bilayer (natural saponite and Li+-SA) sheet, respectively, of water molecules in the interlayer space of the clays. The higher hydration degree in the Li+-exchanged sample is related to the high hydration capacity of this cation. Although the amounts of Li+ and Cs+ are relatively low, their presence clearly influences the shape of the diffractograms. In conclusion, both catalysts used in this study are well
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to abstract protons in the 13.3 pKa 16.5 range. It has been reported that the pKa value of the imidazole NH group is 14.5 [11]. Therefore, the saponites could be appropriate materials to catalyze the propargylation of imidazole at the Nposition. 3.2. Propargylation of imidazole
Fig. 1. X-ray diffractograms of the natural saponite, SA (2 mm fraction), and of the Na+-, Li+- and Cs+-exchanged solids.
ordered saponites, more crystalline in the case of the Li sample. By carrying out the Knoevenagel probe reaction [5], which has been applied to a wide range of microporous materials [1], it was found that the basicity of the clays increases with the radius of the alkaline dopants (Li+SA < Cs+-SA) and the basic sites in the saponites are able
The mass spectra of the reaction products formed confirm that under the reaction conditions, A [MS m/s: 106 (M+), 79 (100), 52, 39] is the only product obtained. Irradiation power values of 300 and 750 W and irradiation time of 1, 3 and 5 min have been selected to carry out the reaction in order to study the influence of both factors on the activity of the catalysts. Fig. 2 shows the yields to N-propargyl imidazole achieved with the two exchanged saponites. These results illustrate an increase of reactivity with irradiation power and time. Yield values of 90% are achieved at 750 W in only 5 min when the Cs+-SA catalyst is employed. Under the experimental conditions, Cs+-SA is ca. twice more active than the Li+-SA, the selectivity being always 100%. This order of activity agrees with the relative basicity of the samples, which increases with the size of the alkaline cation in the clay structure (Li+-SA < Cs+-SA) as it was previously evaluated by Knoevenagel condensation. A blank experiment without catalyst was carried out at 750 W for 5 min. A yield value of 13% to A was achieved, due to the own effect of the microwave irradiation. However, a yield value of 90% is afforded when Cs+-SA is used, which proves the effect of the catalyst in enhancing the yield of the reaction. In order to study the potential of the microwave heating on saponites, additional investigations were made. The temperature of the microwave oven was measured after the different experiments and parallel runs were carried out at those
Fig. 2. Yield to N-propargyl imidazole using 0.1 g of Li+-SA and Cs+-SA under microwave irradiation. Effect of the irradiation power and irradiation time.
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Fig. 3. Yield to N-propargyl imidazole using 0.1 g of Li+-SA and Cs+-SA under thermal activation.
temperatures (308 and 323 K for Li+-SA, and 319 and 340 K for Cs+-SA) under thermal activation in a batch reaction system. The results are shown in Fig. 3. It can be seen that under conventional thermal heating, only a yield value of 55% to A is reached after 2 h of reaction when Cs+-SA is used as a catalyst, this value being the maximum obtained under this type of activation in the studied time period. Nevertheless, only 5 min and 750 W of power are necessary to reach 90% yield under microwave irradiation. Thus, the combined effect of the irradiation power and the alkaline dopant in the saponite, determines the most suitable condition for the preparation of Npropargyl imidazoles with 100% selectivity. 4. Conclusions Propargylation of imidazole has been performed, in absence of any solvent, under microwave heating using alkaline-doped saponites as base catalysts. N-propargyl imidazole is selectively obtained under mild conditions. It has been found that alkalinedoped saponites are active and very selective catalysts for the N-propargylation of imidazole. Both saponites (Li+ and Cs+ samples) present basicity enough to carry out the reaction, and they absorb the microwave radiation enhancing the activity of the sites where the propargylation takes place. Values of 90% of yield and 100% of selectivity are achieved at 750 W of microwave power in only 5 min of reaction. This method can be
extended to the preparation of a number of N-propargyl heterocycles, which are high added-value products. Acknowledgements The authors gratefully thank financial support from the Spanish Ministry of Education and Science and FEDER funds. (Ref. MAT2002-03526) and from Junta de Castilla y Leo´n and FEDER funds (Ref. SA012/04). References [1] J. Weitkamp, M. Hunger, U. Rymsa, Microporous Mesoporous Mater. 48 (2001) 255. [2] H. Hattori, Appl. Catal. A: Gen. 222 (2001) 247. [3] B.F. Sels, D.E. De Vos, P.A. Jacobs, Catal. Rev. 43 (2001) 443. [4] W.F. Ho¨lderich, G. Hetmann, Catal. Today 38 (1997) 227. [5] A. Corma, R.M. Martı´n-Aranda, J. Catal. 130 (1991) 130. [6] P.J. Kooyman, G.C.A. Luijkx, A. Arafat, H. van Bekkum, J. Mol. Catal. A: Chem. 111 (1996) 167. [7] L. Seyfried, F. Garin, G. Maire, J.M. Thie´baux, G. Roussy, J. Catal. 148 (1994) 281. [8] K.A.M. Walker, US Patent 4,059,705 (1997). [9] E. Dı´ez-Barra, A. de la Hoz, A. Loupy, A. Sa´nchez-Migallo´n, Heterocycles 38 (1994) 1367. [10] L.R. Radovic, F. Rodrı´guez-Reinoso, in: P.A. Thrower (Ed.), Chemistry and Physics of the Carbon, 25, Marcel Dekker, New York, 1997, p. 243. [11] T.L. Gilchrist, Heterocyclic Chemistry, second ed., Wiley, New York, 1992.
Microwave enhanced synthesis of N-propargyl derivatives of imidazole A green approach for the preparation of fungicidal compounds Elizabeth Perozo-Rondo´n a, Laureano Costarrosa a, Rosa M. Martı´n-Aranda a,*, Marı´a L. Rojas-Cervantes a, Miguel A. Vicente-Rodrı´guez b a
Departamento de Quı´mica Inorga´nica y Quı´mica Te´cnica, Facultad de Ciencias, UNED, Paseo Senda del Rey no. 9, Madrid 28.040, Spain b Departamento de Quı´mica Inorga´nica, Universidad de Salamanca, Plaza de la Merced s/n, E-37008 Salamanca, Spain Available online 7 December 2005
Abstract N-Propargyl imidazole has been synthesized by Knoevenagel condensation of benzaldehyde with propargyl bromide, assisted by microwave irradiation. Two alkaline-promoted clays (Li+- and Cs+-exchanged saponites) have been used as catalysts. The influence of several factors, such as irradiation power, irradiation time and alkaline promoter has been studied. The catalysts were characterized by XRD and chemical analysis. The basicity enhancement is directly connected to the presence of alkaline metal promoters in the saponite structure. In addition, a significant increase in the conversion values has been found when the reaction is activated by microwave irradiation, as compared with thermal activation. The yield to the N-propargyl imidazole shows a maximum for the Cs+-saponite at 750 W in only 5 min of microwave irradiation. This green and solvent-free procedure can be extended to the preparation of other N-substituted heterocycles, which could serve as precursors in the primary route to pharmaceutical compounds of interest. # 2005 Elsevier B.V. All rights reserved. PACS: 82.65.J Keywords: Basic clays; Microwave irradiation; Propargylation; Imidazole
1. Introduction The development of solid base catalysts for fine chemicals production is nowadays a subject of increasing interest [1,2]. Hydrotalcites [3], zeolites [4] and sepiolites [5], among others have shown interesting behavior as base catalysts. Moreover, new technologies are being employed to accelerate such catalytic reactions under mild conditions. Microwave irradiation is an alternative heating system to conventional heating methods, which affords interesting reactivity under mild conditions and very short reaction times [6,7]. In general, the anionic alkylation of heterocycles is the primary route to produce important fungicidal and anticonvulsant compounds [8]. N-Propargyl heterocycles of type A (Scheme 1) are of interest due to their pharmacological
* Corresponding author. Tel.: +34 1 3987351; fax: +34 1 3986697. E-mail address: [email protected] (R.M. Martı´n-Aranda). 0169-4332/$ – see front matter # 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.apsusc.2005.11.005
applications, but usually, in basic media the reaction between the N-heterocycles and propargyl bromide affords a mixture of N-allyl (B) and N-propargyl (C) derivatives [9]. In the present study, we investigate the effect of the microwave heating on the activity and selectivity of two basic clays in the alkylation of imidazole with propargyl bromide. Clays are known, in microwave terminology as ‘‘lossy’’ materials, which means that they are efficient absorbers of microwave radiation converting it into heat. This allows a reduction of the reaction temperature values and increases the selectivity towards the N-propargyl derivative. 2. Experimental 2.1. Preparation and characterization of alkaline-doped saponites The starting material used in this work is a natural saponite from Yunclillos deposit (province of Toledo, Spain), supplied
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The yield is expressed in terms of the amount of A obtained in wt.%. 2.3. General procedure for conventional heated reactions
Scheme 1. Alkylation of imidazole with propargyl bromide.
by TOLSA, S.A. The 2 mm fraction of the clay was obtained by careful aqueous decantation of the raw material. The chemical weight percent composition of this clay is SiO2: 49.45; Al2O3: 4.72; Fe2O3: 1.29; MgO: 24.34; TiO2: 0.20; MnO: 0.03; CaO: 0.78; Na2O: 0.07; K2O: 0.44 and the loss by ignition is 18.31 wt.%. X-ray diffraction shows that this fraction contains small amounts of sepiolite and quartz. Considering these impurities, the structural formula of saponite, on the basis of 22 oxygen atoms, was found to be: (Si7.42Al0.58) O20 (Mg5.16Fe0.14Al0.26Mn0.004Ti0.02) (OH)4 [Mg0.24Ca0.124Na0.020K0.084]. The cation exchange capacity (CEC) of this sample was 115 meq/100 g of dry clay, and the BET surface was 161 m2/g. Li+-saponite (Li+-SA) and Cs+-saponite (Cs+-SA) were prepared by a two-step synthetic process. First, homoionic Na+-saponite (Na+-SA) was obtained by washing 30 g of saponite (2 mm fraction) three times with 500 mL of 1 M NaCl solution. In the second step, Li+- and Cs+-exchanged solids were prepared by treating the sodium clay with solutions of the corresponding chlorides. 1.4 g of LiCl or 2.6 g of CsCl were added to a suspension containing 10 g of Na+-SA in 500 mL of water. These suspensions were stirred for 24 h and then washed with water until no chloride anions were detected. The composition of the clays was determined by atomic absorption (AA) on a Perkin-Elmer 4100 ZL spectrometer. Crystalline structures of the samples were analyzed by X-ray diffraction (XRD) with a Siemens Krystalloflex D500 diffractometer, using filtered Cu Ka radiation. The basicity of the Li+-SA and Cs+-SA samples was previously evaluated by the Knoevenagel condensation probe reaction, described by Corma and Martı´n-Aranda [5], which has been applied to estimate the basicity of a wide range of microporous solid materials [1,10]. 2.2. General procedure for microwave irradiated reactions Imidazole (4 mmol) and the corresponding clay catalyst (0.1 g) were blended in a Teflon vessel and propargyl bromide (4.5 mmol) was added. The mixture was irradiated in a microwave oven (Sanyo EM881) at different powers (300 and 750 W). The temperature was measured at the end of each run. After cooling, the reaction products were extracted with acetone and filtered. The reaction was followed by gas chromatography in a Konik KNK-3000-HRGC system with a 60 m long BP1 capillary column. The mass spectra were obtained on a Hewlett-Packard HP5871-A spectrometer.
Imidazole (4 mmol) and the catalyst (0.1 g) were mixed in a Pyrex flask and then, propargyl bromide (4.5 mmol) was added. The mixture was heated (in absence of any solvent) up to the reaction temperature. The samples were taken periodically from 15 to 60 min, extracted with acetone, and filtered. The reaction evolution was followed by gas chromatography. 3. Results and discussion 3.1. Characterization of alkaline-doped saponites Li+-SA fixes 0.12 wt.% of Li+ (referred to the dehydrated sample) indicating that 0.138 exchangeable positions are occupied by this cation in the structural formula given above. Cs+-SA fixes 0.97 wt.% of Cs+, equivalent to 0.058 positions in the structural formula given above. This means that under the above experimental conditions about 16% of the exchangeable positions of the clay were effectively exchanged by Li+ and only about 7% by Cs+, the rest of the positions remained occupied by Na+ cations. Although, in both cases, Li+ and Cs+ cations were in excess with respect to the CEC of the clay in the exchanging solution, a high degree of substitution is not expected when exchanging only once with these cations. Higher substitution degrees may be reached by repeating the exchanging processes, but the amounts of Li+ and Cs+ incorporated to the clays were considered acceptable for the purpose of the study (the effect of microwave activation combined with a mild basicity of the catalyst). The X-ray diffraction patterns of the exchanged solids are displayed in Fig. 1. They show the usual patterns of wellordered saponites. The intensity of Na+-SA diffractogram, included for comparison, is very similar to that of the <2 mm fraction of the natural clay, and compared with them, Li+-SA has a more intense (0 0 1) reflection peak, whereas the Cs+SA has a less intense and wider reflection. Thus, the exchanging with Li+ produces a increased ordering of the layers, while the exchanging with Cs+ has an opposite effect. At the same time, the basal spacing of the Na+-SA and Cs+˚ , whereas for the Li+-SA this spacing is SA is close to 12.5 A ˚ , the same as for the natural clay, which close to 14.7 A mainly has alkaline-earth cations in exchangeable positions (see the structural formula given above). The basal spacings agree with the presence of a monolayer (Na+-SA and Cs+SA) or a bilayer (natural saponite and Li+-SA) sheet, respectively, of water molecules in the interlayer space of the clays. The higher hydration degree in the Li+-exchanged sample is related to the high hydration capacity of this cation. Although the amounts of Li+ and Cs+ are relatively low, their presence clearly influences the shape of the diffractograms. In conclusion, both catalysts used in this study are well
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to abstract protons in the 13.3 pKa 16.5 range. It has been reported that the pKa value of the imidazole NH group is 14.5 [11]. Therefore, the saponites could be appropriate materials to catalyze the propargylation of imidazole at the Nposition. 3.2. Propargylation of imidazole
Fig. 1. X-ray diffractograms of the natural saponite, SA (2 mm fraction), and of the Na+-, Li+- and Cs+-exchanged solids.
ordered saponites, more crystalline in the case of the Li sample. By carrying out the Knoevenagel probe reaction [5], which has been applied to a wide range of microporous materials [1], it was found that the basicity of the clays increases with the radius of the alkaline dopants (Li+SA < Cs+-SA) and the basic sites in the saponites are able
The mass spectra of the reaction products formed confirm that under the reaction conditions, A [MS m/s: 106 (M+), 79 (100), 52, 39] is the only product obtained. Irradiation power values of 300 and 750 W and irradiation time of 1, 3 and 5 min have been selected to carry out the reaction in order to study the influence of both factors on the activity of the catalysts. Fig. 2 shows the yields to N-propargyl imidazole achieved with the two exchanged saponites. These results illustrate an increase of reactivity with irradiation power and time. Yield values of 90% are achieved at 750 W in only 5 min when the Cs+-SA catalyst is employed. Under the experimental conditions, Cs+-SA is ca. twice more active than the Li+-SA, the selectivity being always 100%. This order of activity agrees with the relative basicity of the samples, which increases with the size of the alkaline cation in the clay structure (Li+-SA < Cs+-SA) as it was previously evaluated by Knoevenagel condensation. A blank experiment without catalyst was carried out at 750 W for 5 min. A yield value of 13% to A was achieved, due to the own effect of the microwave irradiation. However, a yield value of 90% is afforded when Cs+-SA is used, which proves the effect of the catalyst in enhancing the yield of the reaction. In order to study the potential of the microwave heating on saponites, additional investigations were made. The temperature of the microwave oven was measured after the different experiments and parallel runs were carried out at those
Fig. 2. Yield to N-propargyl imidazole using 0.1 g of Li+-SA and Cs+-SA under microwave irradiation. Effect of the irradiation power and irradiation time.
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Fig. 3. Yield to N-propargyl imidazole using 0.1 g of Li+-SA and Cs+-SA under thermal activation.
temperatures (308 and 323 K for Li+-SA, and 319 and 340 K for Cs+-SA) under thermal activation in a batch reaction system. The results are shown in Fig. 3. It can be seen that under conventional thermal heating, only a yield value of 55% to A is reached after 2 h of reaction when Cs+-SA is used as a catalyst, this value being the maximum obtained under this type of activation in the studied time period. Nevertheless, only 5 min and 750 W of power are necessary to reach 90% yield under microwave irradiation. Thus, the combined effect of the irradiation power and the alkaline dopant in the saponite, determines the most suitable condition for the preparation of Npropargyl imidazoles with 100% selectivity. 4. Conclusions Propargylation of imidazole has been performed, in absence of any solvent, under microwave heating using alkaline-doped saponites as base catalysts. N-propargyl imidazole is selectively obtained under mild conditions. It has been found that alkalinedoped saponites are active and very selective catalysts for the N-propargylation of imidazole. Both saponites (Li+ and Cs+ samples) present basicity enough to carry out the reaction, and they absorb the microwave radiation enhancing the activity of the sites where the propargylation takes place. Values of 90% of yield and 100% of selectivity are achieved at 750 W of microwave power in only 5 min of reaction. This method can be
extended to the preparation of a number of N-propargyl heterocycles, which are high added-value products. Acknowledgements The authors gratefully thank financial support from the Spanish Ministry of Education and Science and FEDER funds. (Ref. MAT2002-03526) and from Junta de Castilla y Leo´n and FEDER funds (Ref. SA012/04). References [1] J. Weitkamp, M. Hunger, U. Rymsa, Microporous Mesoporous Mater. 48 (2001) 255. [2] H. Hattori, Appl. Catal. A: Gen. 222 (2001) 247. [3] B.F. Sels, D.E. De Vos, P.A. Jacobs, Catal. Rev. 43 (2001) 443. [4] W.F. Ho¨lderich, G. Hetmann, Catal. Today 38 (1997) 227. [5] A. Corma, R.M. Martı´n-Aranda, J. Catal. 130 (1991) 130. [6] P.J. Kooyman, G.C.A. Luijkx, A. Arafat, H. van Bekkum, J. Mol. Catal. A: Chem. 111 (1996) 167. [7] L. Seyfried, F. Garin, G. Maire, J.M. Thie´baux, G. Roussy, J. Catal. 148 (1994) 281. [8] K.A.M. Walker, US Patent 4,059,705 (1997). [9] E. Dı´ez-Barra, A. de la Hoz, A. Loupy, A. Sa´nchez-Migallo´n, Heterocycles 38 (1994) 1367. [10] L.R. Radovic, F. Rodrı´guez-Reinoso, in: P.A. Thrower (Ed.), Chemistry and Physics of the Carbon, 25, Marcel Dekker, New York, 1997, p. 243. [11] T.L. Gilchrist, Heterocyclic Chemistry, second ed., Wiley, New York, 1992.