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Multi-component carbon–carbon bond forming Mannich reaction catalyzed by yttria–zirconia based Lewis acid
Catalysis Communications 9 (2008) 2445–2448
Contents lists available at ScienceDirect
Catalysis Communications journal homepage: www.elsevier.com/locate/catcom
Multi-component carbon–carbon bond forming Mannich reaction catalyzed by yttria–zirconia based Lewis acid S. Ramalingam, Pradeep Kumar * Division of Organic Chemistry, National Chemical Laboratory, Pune 411 008, India
a r t i c l e
i n f o
Article history: Received 25 March 2008 Received in revised form 9 June 2008 Accepted 11 June 2008 Available online 20 June 2008
a b s t r a c t A direct three component Mannich-type reaction of aldehyde, amine, and ketone (without silyl enolates) were efficiently catalyzed by yttria–zirconia based strong Lewis acid in aqueous acetonitrile. Ó 2008 Elsevier B.V. All rights reserved.
Keywords: Mannich reaction b-Amino carbonyls Yttria–zirconia based Lewis acid Multi-component reaction
1. Introduction Multi-component reactions performed either on a solid or in solution phase [1] not only have emerged as a powerful tool in combinatorial chemistry but also has the power to rapidly build complex organic molecules. Many unique structures can be attained rapidly when three or more reactants are combined in a single step to afford new compounds possessing the combined features of the building blocks [2]. The Mannich reaction provides one of the most basic and useful methods for the synthesis of such compound. In such a reaction, an amine, two carbonyl compounds in presence of a acid (or base) catalyst are used to produce b-amino carbonyl compound. Numerous kinds of activators have been developed to accelerate the efficient formation of this carbon–carbon bond forming reaction [3,4]. b-Amino carbonyls are important precursors for b-lactam and amino acid [5] and they also serve as versatile synthetic intermediate for various pharmaceuticals and natural products. Various methods have been reported in the literature to synthesize b-amino carbonyls employing a variety of catalysts. Some of the methods developed are based on the kind of carbonyls (ketones or silyl enol ethers) used to react with aldimines [6–10]. In recent years, organic reactions in water or combination of water and organic solvents, without using harmful organic solvents are of great importance, especially in relation to today’s environmental concerns. On the other hand, organic reactions using reusable solid catalysts have also received much attention because of their prac* Corresponding author. Tel.: +91 20 25902050; fax: +91 20 25902629. E-mail address: [email protected] (P. Kumar). 1566-7367/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.catcom.2008.06.011
tical advantage. Therefore, organic reactions using solid Lewis acid catalysts in water or the combination of water and organic solvents will be an ideal methodology. Because of the deactivation of most of the solid acid catalysts, in water as solvent, the combination of water and organic solvents were preferred. Many methods developed in aqueous media use preformed aldimines and reactive silyl enolates to prepare b-amino carbonyl [11–14]. Though conventional protocols for three component Mannich type reaction of aldehydes, amines and ketones in organic solvents include some severe side reactions and have some substrate limitations, especially for enolizable aliphatic aldehydes. Kobayashi and co-workers reported the preparation of b-amino carbonyls by direct three component asymmetric Mannich reaction using different amines, aldehydes and ketones and catalyst in aqueous media (colloidal dispersion system created by a Brönsted acid surfactant, p-dodecylbenzene sulfonic acid (DBSA) and polymer-supported sulfonic acid). Adrian and coworkers developed TiCl4/DIPEA mediated stereoselective approach to synthesize the b-amino carbonyls [15]. Jiang and coworkers used the ionic liquid as catalyst and solvents to synthesize b-amino carbonyls by directly coupling the aldimines with ketones [16]. List and co-workers reported the L-proline based three component coupling to prepare b-amino carbonyl compounds [17]. Although Brönsted acid surfactant, proline catalyzed direct three component coupling reaction to prepare b-amino carbonyls are known, the recyclability of these catalyst in water becomes a problem. These methods are associated with another drawback that the silyl enolates which is prepared from the corresponding carbonyl compounds needs anhydrous conditions. From atom economy and practical points of view, it is desirable to develop an efficient reusable catalytic system for such reaction in which
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S. Ramalingam, P. Kumar / Catalysis Communications 9 (2008) 2445–2448
the parent carbonyls (for enol ethers) compounds can be directly used. In continuation of our research interest on the application of yttria–zirconia based Lewis acid catalysts for various organic transformations [18,19], we herein report the synthesis of b-amino carbonyls by direct three component coupling reaction of an aldehyde, amine and carbonyl compound.
2. Experimental 2.1. Materials and equipment All reactions were run under air atmosphere. Chromatographic separations were done using EM SiO2-60 (300–400 mesh) as the stationary phase. The IR spectra were recorded on Perkin-Elmer spectrophotometer 683B or 1605FT-IR and adsorptions are expressed in cm 1. The 1H and 13C-NMR spectra were recorded on Brucker AC-200, MSL-300, DRX-500 MHz instruments using TMS as the internal standard. Mass spectra were obtained with Finningen MAT mass spectrometer. Elemental analyses were carried out with a carlo Erba CHNS-O analyzer. The diffractogram of X-ray powder diffraction pattern of the catalyst was recorded on a Rigaku diffractometer model D/Max IIIVC with N-filtered Cu Ka radiation. FTIR spectrum of pyridine adsorbed on the yttrium-based catalyst recorded on a Nicolet 60 SXB FTIR spectrometer. TPD profile (ammonia) of the yttrium-based catalyst was recorded on a Sorbs tar apparatus. Determination of specific surface area was carried out by BET (Brunner–Emmett–Teller) N2 adsorption using a Omnisorp 100CX apparatus. Solvents were purified and dried by standard procedures before use according to reported procedure [20]. Petroleum ether refers to the fraction collected in boiling range 60–80 °C. The catalyst was prepared and characterized in following manner and it was calcined at 573 K before use.
Fig. 1. X-ray powder diffraction pattern of the yttrium based catalyst prior to (a) and after (b) sulfation. The diffraction was recorded on Rigaku diffractometer, model D/Max IIIVC, with Ni-filtered Ca2a radiation 1 = intensity (arbitrary units).
Fig. 2. FTIR spectrum of pyridine adsorbed on the yttrium based catalyst, recorded on a Nicolet 60 SXB FTIR spectrometer A = absorption (arbitrary units).
2.2. Synthesis of catalyst The catalyst was prepared by mixing aqueous solutions of yttrium nitrate and zirconyl nitrate in the mole ratio 16:84, to which aqueous ammonia (28%) was added under vigorous stirring until a pH of 8.5 was achieved and precipitate was formed. Washing with deionized water, drying at 110 °C for 24 h, treating with sulfuric acid (4 M), drying at 120 °C and subsequent programmed calcinations of 500 °C for 3 h at a heating rate of 2 °C min 1 resulted in a highly acidic material. The chemical composition of the final catalyst (determined by XRF technique) was found to be 82.6 mol% Zr, 15.6 mol% Y and 1.8 mol% S. 2.3. Characterization of the catalyst The physicochemical characterization of catalyst was carried out by titration, temperature programmed desorption (TPD), scanning electron microscopy (SEM) and N2 adsorption technique. The X-ray powder diffraction profile of the catalyst shows the formation of a cubic phase (Fig. 1). The IR spectra of pyridine adsorbed on the catalyst show absorption band at 1640, 1605, 1577, 1542, 1490 and 1444 cm 1 (Fig. 2). The strong absorption bands at 1605 and at 1444 cm 1 indicate the presence of coordinated pyridine at the Lewis acid sites of the catalyst. The weak absorption at 1542 cm 1 attributed to pyridinium ion [21] indicates the presence of a few Brönsted acid sites. The potentiometric titration of the acid sites with n-butylamine in non-aqueous medium (Fig. 3) shows the influence of yttrium in enhancing the number of acid sites [22]. The amount of n-butylamine consumed was 7.7 mol equiv. g 1 for the yttrium-based catalyst compared to 5.8 mol equiv. g 1 for the yt-
Fig. 3. Potentiometric titration curve of the sulfated catalyst with yttrium (curve a) and without yttrium (curve b) in acetonitrile. For details see Ref. [7]. n = number molar equivalent of n-butylamine per gram.
trium free catalyst. The presence of very strong acid sites in the catalyst is indicated by the peak maxima at 530 °C in the TPD profile (Fig. 4) [23]. The scanning electron micrograph of sample shows the presence of uniform-sized (around 0.3 lm) particles (Fig. 5). The surface area of the sample determined by the BET (Brunner–Emmett–Teller) method was 150 m2 g 1. The lattice defects caused by the incorporation of yttrium in the Zr4+ sites appear to enhance the number and strength of the Lewis acid sites of the catalyst.
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S. Ramalingam, P. Kumar / Catalysis Communications 9 (2008) 2445–2448
Table 1 One pot synthesis of b-amino carbonyl compounda by three component coupling of amine, aldehyde and ketone Entry
R1
R2
R3
R4
Ketone (equiv.)
Time (h)
Yieldb (%)
1 2
C6H5 3,4,5(OMe)3–C6H2 3,4,5(OMe)3–C6H2 3,4,5(OMe)3–C6H2 3,4,5(OMe)3–C6H2
C6H5 4-Cl– C6H4 3-Cl–4F–C6H4 4-OMe– C6H4 2-Me– C6H4 4-OMe– C6H4
H H
C6H5 C6H5
1.2 1.2
10 12
83 79
H
C6H5
1.2
10
74
H
C6H5
1.2
12
87
H
2-Cl– C6H4 C6H5
1.2
18
69
1.2
12
82
4-OMe– C6H4 C6H5
H
1.2
20
57
H
4-OH– C6H4 C6H5
1.2
22
45
C6H5CH2
H
C6H5
1.2
11
48
H
–(CH2)5– C6H5
2.0 1.2
11 24
78 61
H
C6H5
1.2
12
35
MeCO MeCO
OEt Me
1.2 1.2
20 20
– –
3 4 5 6
Fig. 4. TPD profile (ammonia) of the yttrium-based catalyst, recorded on a Sorbs tar apparatus, Institutes of Isotopes, Hungary, with He as the carried gas, a flow rate of 50 mL min 1, and a heating rate of 10 K min 1 from room temperature to 625 °C. NH3 = Amount of ammonia desorbed (arbitrary units).
O 4-Me–C6H4
7 8
N O
Cl
9
O
10 11
C6H5 2-Pentenal
12
isovaleraldehyde C6H5 C6H5
13 14 a b
H
C6H5 4-Cl– C6H4 4-Cl– C6H4 C6H5 C6H5
The products were characterized by spectroscopic method (1H and Isolated yields.
13
C NMR).
over anhydrous Na2SO4 and concentrated to give the crude product, which was purified by silica gel column chromatography using petroleum ether:EtOAc (80:20) as eluent to give the pure b-amino carbonyl (see Scheme 1). 3. Results and discussion
Fig. 5. Scanning electron micrograph of the catalyst.
2.4. General procedure for the synthesis of b-amino carbonyls using yttria–zirconia based Lewis acid A mixture of aldehyde (1 mmol), amine (1 mmol) and ketone (1.2 mmol) was stirred at 65 °C in presence of 10 mol% of yttria– zirconia Lewis acid catalyst in aqueous CH3CN (CH3CN:H2O, 9:1) for the indicated time mentioned in Table 1. The reaction completion was monitored by TLC. The reaction mixture was filtered in hot condition for the catalyst recovery, and the filtrate was diluted with water and extracted with CH2Cl2 (3 25 ml). The combined organic layer was washed with water and brine solution, dried
R1CHO
+
R2 NH2
+
R4
R3 O
yttria-zirconia 10mol%
In a typical procedure a 1:1:1.2 mixture of 4-methylbenzaldehyde, p-anisidine and p-hydroxyacetophenone with 10 mol% of yttria–zirconia based Lewis acid catalyst in aqueous CH3CN was refluxed at 65 °C to give the Mannich product in 57% yield (Table 1, entry 7) in contrast to <5% yield with HCl catalyzed reaction in EtOH (24 h) [1]. The present procedure for Mannich reaction is quite general as a wide range of structurally varied aldehydes such as aromatic aldehydes, aliphatic aldehydes, a,b-unsaturated aldehydes, and heteroaromatic aldehydes underwent Mannich reaction with various amines and ketones in moderate to good yields (Table 1). A possible mechanism of the Mannich reaction using yttria–zirconia as Lewis acid catalyst is shown in Scheme 2. Presumably the carbonyl compound gets activated by the coordination of oxygen atom with the Lewis acid sites of the catalyst thus facilitating the formation of an enolate first which then reacts with the imine and thus eventually leading to the formation of the desired product. In order to evaluate the efficacy of catalyst with aliphatic alde-
R2 NH
aq CH3CN, 65o C R1 R3
O
R1 = Substituted aromatics. Heteroaromatics and aliphatics. 2 R4 R3 = Substituted aromatics. R = Aliphatic or H. R4 = Substituted aromatics
Scheme 1. A direct one-pot synthesis of b-amino carbonyls.
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S. Ramalingam, P. Kumar / Catalysis Communications 9 (2008) 2445–2448
R3
H+
R2
R2
N + R1
H
NH
yttria-zirconia R4
O
5% aq. acetonitrile LA 65oC
O
R1
R4 R3
Scheme 2. Possible mechanism of the Mannich reaction using yttria–zirconia.
hydes, isovaleraldehyde and 2-pentenal were examined. While isovaleraldehyde gave only 35% of yield of the desired product, pentenal gave somewhat better yield (61%) with 4-chlorobenzaldehyde and acetophenone (Table 1, entry 11 and 12). b-Keto esters and acetyl acetone failed to react under our conditions. As can be seen from the Table 1, while reaction worked smoothly with 1.2 equiv. of aromatic ketones, the use of 2 equiv. was required in the case of cyclohexanone for the completion of reaction (Table 1, entry 10). Another notable feature of this methodology while comparing with the recently reported method [8–13,15] is that the preparation of preformed aldimines and reactive silyl enolates from carbonyls could be avoided and parent ketones can be used directly. The catalyst was found to be comparable in terms of conversion, yield and selectivity of the desired product with the reported methods [14,16,17]. Moreover, these reactions which proceed sluggishly in organic solvents, reacted faster when we add 5–10% of water. When the ratio of water was increased to 20%, the recovery of the catalyst with original activity becomes a problem.
4. Recyclability of the catalyst In order to evaluate the reusability and leaching of the catalyst in aqueous acetonitrile, experiments were carried by condensation of benzaldehyde, aniline and acetophenone, one with 5% of water in acetonitrile and another with 20% water in acetonitrile as solvent. The first, second and third cycles of the first experiment gave yields such as 83%, 80% and 75% of desired product with increasing reaction time of 10, 12 and 15 h with 100% conversion. After the third recycle the catalyst needed reactivation. The experiment which was carried out with 20% water in acetonitrile gave 80% yield with the reaction time of 15 h. While reusing catalyst which was recovered from the experiments with 20% of water in acetonitrile, it gave only 5% of the desired product with recovery of starting material as major compound even after 24 h of reaction time. But after reactivation by calcination at 573 K, the same catalyst which is recovered from 20% water in acetonitrile gave 78% of the desired product with the conversion of 100%. It is concluded from the above experiments that less proportion of water (5%) is favorable for the recovery of catalyst retaining its original activity. The addition of excess of water could be disturbing the Lewis acidity by collapsing the acid sites of the catalyst. The recycling of the catalyst showed that there was no leaching of the metal as there was no drop in the conversion rate in the subsequent recycling reactions.
5. Conclusion In summary, three component Mannich-type reaction of aldehyde, amine, and ketone is efficiently catalyzed by yttria–zirconia based Lewis acid in aqueous CH3CN. The reaction works well with a wide range of structural variations in all the three components. The important feature of this methodology is the easy preparation of the catalyst and its reactivation (by calcination) after the reaction. Acknowledgement The authors are thankful to Dr M. K. Dongare of catalysis division of NCL, Pune for providing the catalysy and Dr. Ganesh Pandey, HOD, Division of Organic Chemistry for his support and encouragement. This is NCL communication No. 6708. References [1] S. Kobayashi, R. Matusubara, Y. Nakamura, H. Kitagawa, M. Sugiura, J. Am. Chem. Soc. 125 (2003) 2507. [2] S. Kobayashi, Curr. Opin. Chem. Biol. 4 (2000) 338. [3] K. Ishihara, M. Miyata, K. Hattori, T. Tada, H. Yamamoto, J. Am. Chem. Soc. 116 (1994) 10520. [4] K. Miura, K. Tamaki, T. Nakagawa, A. Hosomi, Angew. Chem. Int. Ed. Engl. 39 (2000) 1958. [5] M. Arend, B. Westermann, N. Risch, Angew. Chem. Int. Ed. Engl. 37 (1998) 1045. [6] S. Koboyashi, K. Manabe, Acc. Chem. Res 35 (2002) 209. [7] D.E. Bergbreiter, Chem. Rev. 201 (2002) 3345. [8] H. Ishitani, M. Ueno, S. Kabayashi, J. Am. Chem. Soc. 122 (2000) 8180. [9] H. Ishitani, S. Kobayashi, Org. Lett. 4 (2002) 3395. [10] B.C. Maity, V.G. Puranik, A. Sarkar, Synlett 3 (2002) 504. [11] T.-P. Loh, S.-L. Chen, Org. Lett. 21 (2002) 3647. [12] K. Manabe, Y. Mori, S. Koboyashi, Tetrahedron 57 (2001) 2537. [13] S. Iimura, D. Nobutou, K. Manabe, S. Kobayashi, Chem. Commun. (2003) 1644. and references therein. [14] T. Akiyama, J. Takaya, H. Kagoshima, Tetrahedron Lett. 42 (2001) 4025. [15] A.L. Joffe, T.M. Thomas, J.C. Adrian Jr., Tetrahedron Lett. 45 (2004) 5087. [16] G. Zhao, T. Jiang, H. Gao, B. Han, J. Huang, B. Sun, Green Chemistry 6 (2004) 75. [17] B. List, J. Am. Chem. Soc. 122 (2000) 9336. [18] A. Keshava raja, V.R. Hegde, B. Pandey, A.V. Ramaswamy, P. Kumar, T. Ravindranathan, Angew. Chem. Int. Ed. Engl. 34 (1995) 2143. [19] P. Kumar, R.K. Pandey, M.S. Bodas, S.P. Dagade, M.K. Dongare, A.V. Ramaswamy, J. Mol. Catal. A. Chem. 181 (2002) 207. and references therein. [20] B.S. Furniss, A.J. Hannaford, V. Rogeres, P.W.G. Smith, A.R. Tatchell (Eds.), Vogel’s Text book Practical Organic Chemistry, fourth ed., ELBS/Longman, London, 1978. [21] N. Mizuno, H. Fujii, H. Igarashi, M. Misono, J. Am. Chem. Soc. 114 (1992) 7151. [22] R. Cid, Gid, G. Pecchi, Appl. Catal. 14 (1985) 15. [23] M.J.F.M. Verhaak, A.J. Van Dillen, J.W. Geus, Appl. Catal. 105 (1993) 251.
Contents lists available at ScienceDirect
Catalysis Communications journal homepage: www.elsevier.com/locate/catcom
Multi-component carbon–carbon bond forming Mannich reaction catalyzed by yttria–zirconia based Lewis acid S. Ramalingam, Pradeep Kumar * Division of Organic Chemistry, National Chemical Laboratory, Pune 411 008, India
a r t i c l e
i n f o
Article history: Received 25 March 2008 Received in revised form 9 June 2008 Accepted 11 June 2008 Available online 20 June 2008
a b s t r a c t A direct three component Mannich-type reaction of aldehyde, amine, and ketone (without silyl enolates) were efficiently catalyzed by yttria–zirconia based strong Lewis acid in aqueous acetonitrile. Ó 2008 Elsevier B.V. All rights reserved.
Keywords: Mannich reaction b-Amino carbonyls Yttria–zirconia based Lewis acid Multi-component reaction
1. Introduction Multi-component reactions performed either on a solid or in solution phase [1] not only have emerged as a powerful tool in combinatorial chemistry but also has the power to rapidly build complex organic molecules. Many unique structures can be attained rapidly when three or more reactants are combined in a single step to afford new compounds possessing the combined features of the building blocks [2]. The Mannich reaction provides one of the most basic and useful methods for the synthesis of such compound. In such a reaction, an amine, two carbonyl compounds in presence of a acid (or base) catalyst are used to produce b-amino carbonyl compound. Numerous kinds of activators have been developed to accelerate the efficient formation of this carbon–carbon bond forming reaction [3,4]. b-Amino carbonyls are important precursors for b-lactam and amino acid [5] and they also serve as versatile synthetic intermediate for various pharmaceuticals and natural products. Various methods have been reported in the literature to synthesize b-amino carbonyls employing a variety of catalysts. Some of the methods developed are based on the kind of carbonyls (ketones or silyl enol ethers) used to react with aldimines [6–10]. In recent years, organic reactions in water or combination of water and organic solvents, without using harmful organic solvents are of great importance, especially in relation to today’s environmental concerns. On the other hand, organic reactions using reusable solid catalysts have also received much attention because of their prac* Corresponding author. Tel.: +91 20 25902050; fax: +91 20 25902629. E-mail address: [email protected] (P. Kumar). 1566-7367/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.catcom.2008.06.011
tical advantage. Therefore, organic reactions using solid Lewis acid catalysts in water or the combination of water and organic solvents will be an ideal methodology. Because of the deactivation of most of the solid acid catalysts, in water as solvent, the combination of water and organic solvents were preferred. Many methods developed in aqueous media use preformed aldimines and reactive silyl enolates to prepare b-amino carbonyl [11–14]. Though conventional protocols for three component Mannich type reaction of aldehydes, amines and ketones in organic solvents include some severe side reactions and have some substrate limitations, especially for enolizable aliphatic aldehydes. Kobayashi and co-workers reported the preparation of b-amino carbonyls by direct three component asymmetric Mannich reaction using different amines, aldehydes and ketones and catalyst in aqueous media (colloidal dispersion system created by a Brönsted acid surfactant, p-dodecylbenzene sulfonic acid (DBSA) and polymer-supported sulfonic acid). Adrian and coworkers developed TiCl4/DIPEA mediated stereoselective approach to synthesize the b-amino carbonyls [15]. Jiang and coworkers used the ionic liquid as catalyst and solvents to synthesize b-amino carbonyls by directly coupling the aldimines with ketones [16]. List and co-workers reported the L-proline based three component coupling to prepare b-amino carbonyl compounds [17]. Although Brönsted acid surfactant, proline catalyzed direct three component coupling reaction to prepare b-amino carbonyls are known, the recyclability of these catalyst in water becomes a problem. These methods are associated with another drawback that the silyl enolates which is prepared from the corresponding carbonyl compounds needs anhydrous conditions. From atom economy and practical points of view, it is desirable to develop an efficient reusable catalytic system for such reaction in which
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S. Ramalingam, P. Kumar / Catalysis Communications 9 (2008) 2445–2448
the parent carbonyls (for enol ethers) compounds can be directly used. In continuation of our research interest on the application of yttria–zirconia based Lewis acid catalysts for various organic transformations [18,19], we herein report the synthesis of b-amino carbonyls by direct three component coupling reaction of an aldehyde, amine and carbonyl compound.
2. Experimental 2.1. Materials and equipment All reactions were run under air atmosphere. Chromatographic separations were done using EM SiO2-60 (300–400 mesh) as the stationary phase. The IR spectra were recorded on Perkin-Elmer spectrophotometer 683B or 1605FT-IR and adsorptions are expressed in cm 1. The 1H and 13C-NMR spectra were recorded on Brucker AC-200, MSL-300, DRX-500 MHz instruments using TMS as the internal standard. Mass spectra were obtained with Finningen MAT mass spectrometer. Elemental analyses were carried out with a carlo Erba CHNS-O analyzer. The diffractogram of X-ray powder diffraction pattern of the catalyst was recorded on a Rigaku diffractometer model D/Max IIIVC with N-filtered Cu Ka radiation. FTIR spectrum of pyridine adsorbed on the yttrium-based catalyst recorded on a Nicolet 60 SXB FTIR spectrometer. TPD profile (ammonia) of the yttrium-based catalyst was recorded on a Sorbs tar apparatus. Determination of specific surface area was carried out by BET (Brunner–Emmett–Teller) N2 adsorption using a Omnisorp 100CX apparatus. Solvents were purified and dried by standard procedures before use according to reported procedure [20]. Petroleum ether refers to the fraction collected in boiling range 60–80 °C. The catalyst was prepared and characterized in following manner and it was calcined at 573 K before use.
Fig. 1. X-ray powder diffraction pattern of the yttrium based catalyst prior to (a) and after (b) sulfation. The diffraction was recorded on Rigaku diffractometer, model D/Max IIIVC, with Ni-filtered Ca2a radiation 1 = intensity (arbitrary units).
Fig. 2. FTIR spectrum of pyridine adsorbed on the yttrium based catalyst, recorded on a Nicolet 60 SXB FTIR spectrometer A = absorption (arbitrary units).
2.2. Synthesis of catalyst The catalyst was prepared by mixing aqueous solutions of yttrium nitrate and zirconyl nitrate in the mole ratio 16:84, to which aqueous ammonia (28%) was added under vigorous stirring until a pH of 8.5 was achieved and precipitate was formed. Washing with deionized water, drying at 110 °C for 24 h, treating with sulfuric acid (4 M), drying at 120 °C and subsequent programmed calcinations of 500 °C for 3 h at a heating rate of 2 °C min 1 resulted in a highly acidic material. The chemical composition of the final catalyst (determined by XRF technique) was found to be 82.6 mol% Zr, 15.6 mol% Y and 1.8 mol% S. 2.3. Characterization of the catalyst The physicochemical characterization of catalyst was carried out by titration, temperature programmed desorption (TPD), scanning electron microscopy (SEM) and N2 adsorption technique. The X-ray powder diffraction profile of the catalyst shows the formation of a cubic phase (Fig. 1). The IR spectra of pyridine adsorbed on the catalyst show absorption band at 1640, 1605, 1577, 1542, 1490 and 1444 cm 1 (Fig. 2). The strong absorption bands at 1605 and at 1444 cm 1 indicate the presence of coordinated pyridine at the Lewis acid sites of the catalyst. The weak absorption at 1542 cm 1 attributed to pyridinium ion [21] indicates the presence of a few Brönsted acid sites. The potentiometric titration of the acid sites with n-butylamine in non-aqueous medium (Fig. 3) shows the influence of yttrium in enhancing the number of acid sites [22]. The amount of n-butylamine consumed was 7.7 mol equiv. g 1 for the yttrium-based catalyst compared to 5.8 mol equiv. g 1 for the yt-
Fig. 3. Potentiometric titration curve of the sulfated catalyst with yttrium (curve a) and without yttrium (curve b) in acetonitrile. For details see Ref. [7]. n = number molar equivalent of n-butylamine per gram.
trium free catalyst. The presence of very strong acid sites in the catalyst is indicated by the peak maxima at 530 °C in the TPD profile (Fig. 4) [23]. The scanning electron micrograph of sample shows the presence of uniform-sized (around 0.3 lm) particles (Fig. 5). The surface area of the sample determined by the BET (Brunner–Emmett–Teller) method was 150 m2 g 1. The lattice defects caused by the incorporation of yttrium in the Zr4+ sites appear to enhance the number and strength of the Lewis acid sites of the catalyst.
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S. Ramalingam, P. Kumar / Catalysis Communications 9 (2008) 2445–2448
Table 1 One pot synthesis of b-amino carbonyl compounda by three component coupling of amine, aldehyde and ketone Entry
R1
R2
R3
R4
Ketone (equiv.)
Time (h)
Yieldb (%)
1 2
C6H5 3,4,5(OMe)3–C6H2 3,4,5(OMe)3–C6H2 3,4,5(OMe)3–C6H2 3,4,5(OMe)3–C6H2
C6H5 4-Cl– C6H4 3-Cl–4F–C6H4 4-OMe– C6H4 2-Me– C6H4 4-OMe– C6H4
H H
C6H5 C6H5
1.2 1.2
10 12
83 79
H
C6H5
1.2
10
74
H
C6H5
1.2
12
87
H
2-Cl– C6H4 C6H5
1.2
18
69
1.2
12
82
4-OMe– C6H4 C6H5
H
1.2
20
57
H
4-OH– C6H4 C6H5
1.2
22
45
C6H5CH2
H
C6H5
1.2
11
48
H
–(CH2)5– C6H5
2.0 1.2
11 24
78 61
H
C6H5
1.2
12
35
MeCO MeCO
OEt Me
1.2 1.2
20 20
– –
3 4 5 6
Fig. 4. TPD profile (ammonia) of the yttrium-based catalyst, recorded on a Sorbs tar apparatus, Institutes of Isotopes, Hungary, with He as the carried gas, a flow rate of 50 mL min 1, and a heating rate of 10 K min 1 from room temperature to 625 °C. NH3 = Amount of ammonia desorbed (arbitrary units).
O 4-Me–C6H4
7 8
N O
Cl
9
O
10 11
C6H5 2-Pentenal
12
isovaleraldehyde C6H5 C6H5
13 14 a b
H
C6H5 4-Cl– C6H4 4-Cl– C6H4 C6H5 C6H5
The products were characterized by spectroscopic method (1H and Isolated yields.
13
C NMR).
over anhydrous Na2SO4 and concentrated to give the crude product, which was purified by silica gel column chromatography using petroleum ether:EtOAc (80:20) as eluent to give the pure b-amino carbonyl (see Scheme 1). 3. Results and discussion
Fig. 5. Scanning electron micrograph of the catalyst.
2.4. General procedure for the synthesis of b-amino carbonyls using yttria–zirconia based Lewis acid A mixture of aldehyde (1 mmol), amine (1 mmol) and ketone (1.2 mmol) was stirred at 65 °C in presence of 10 mol% of yttria– zirconia Lewis acid catalyst in aqueous CH3CN (CH3CN:H2O, 9:1) for the indicated time mentioned in Table 1. The reaction completion was monitored by TLC. The reaction mixture was filtered in hot condition for the catalyst recovery, and the filtrate was diluted with water and extracted with CH2Cl2 (3 25 ml). The combined organic layer was washed with water and brine solution, dried
R1CHO
+
R2 NH2
+
R4
R3 O
yttria-zirconia 10mol%
In a typical procedure a 1:1:1.2 mixture of 4-methylbenzaldehyde, p-anisidine and p-hydroxyacetophenone with 10 mol% of yttria–zirconia based Lewis acid catalyst in aqueous CH3CN was refluxed at 65 °C to give the Mannich product in 57% yield (Table 1, entry 7) in contrast to <5% yield with HCl catalyzed reaction in EtOH (24 h) [1]. The present procedure for Mannich reaction is quite general as a wide range of structurally varied aldehydes such as aromatic aldehydes, aliphatic aldehydes, a,b-unsaturated aldehydes, and heteroaromatic aldehydes underwent Mannich reaction with various amines and ketones in moderate to good yields (Table 1). A possible mechanism of the Mannich reaction using yttria–zirconia as Lewis acid catalyst is shown in Scheme 2. Presumably the carbonyl compound gets activated by the coordination of oxygen atom with the Lewis acid sites of the catalyst thus facilitating the formation of an enolate first which then reacts with the imine and thus eventually leading to the formation of the desired product. In order to evaluate the efficacy of catalyst with aliphatic alde-
R2 NH
aq CH3CN, 65o C R1 R3
O
R1 = Substituted aromatics. Heteroaromatics and aliphatics. 2 R4 R3 = Substituted aromatics. R = Aliphatic or H. R4 = Substituted aromatics
Scheme 1. A direct one-pot synthesis of b-amino carbonyls.
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S. Ramalingam, P. Kumar / Catalysis Communications 9 (2008) 2445–2448
R3
H+
R2
R2
N + R1
H
NH
yttria-zirconia R4
O
5% aq. acetonitrile LA 65oC
O
R1
R4 R3
Scheme 2. Possible mechanism of the Mannich reaction using yttria–zirconia.
hydes, isovaleraldehyde and 2-pentenal were examined. While isovaleraldehyde gave only 35% of yield of the desired product, pentenal gave somewhat better yield (61%) with 4-chlorobenzaldehyde and acetophenone (Table 1, entry 11 and 12). b-Keto esters and acetyl acetone failed to react under our conditions. As can be seen from the Table 1, while reaction worked smoothly with 1.2 equiv. of aromatic ketones, the use of 2 equiv. was required in the case of cyclohexanone for the completion of reaction (Table 1, entry 10). Another notable feature of this methodology while comparing with the recently reported method [8–13,15] is that the preparation of preformed aldimines and reactive silyl enolates from carbonyls could be avoided and parent ketones can be used directly. The catalyst was found to be comparable in terms of conversion, yield and selectivity of the desired product with the reported methods [14,16,17]. Moreover, these reactions which proceed sluggishly in organic solvents, reacted faster when we add 5–10% of water. When the ratio of water was increased to 20%, the recovery of the catalyst with original activity becomes a problem.
4. Recyclability of the catalyst In order to evaluate the reusability and leaching of the catalyst in aqueous acetonitrile, experiments were carried by condensation of benzaldehyde, aniline and acetophenone, one with 5% of water in acetonitrile and another with 20% water in acetonitrile as solvent. The first, second and third cycles of the first experiment gave yields such as 83%, 80% and 75% of desired product with increasing reaction time of 10, 12 and 15 h with 100% conversion. After the third recycle the catalyst needed reactivation. The experiment which was carried out with 20% water in acetonitrile gave 80% yield with the reaction time of 15 h. While reusing catalyst which was recovered from the experiments with 20% of water in acetonitrile, it gave only 5% of the desired product with recovery of starting material as major compound even after 24 h of reaction time. But after reactivation by calcination at 573 K, the same catalyst which is recovered from 20% water in acetonitrile gave 78% of the desired product with the conversion of 100%. It is concluded from the above experiments that less proportion of water (5%) is favorable for the recovery of catalyst retaining its original activity. The addition of excess of water could be disturbing the Lewis acidity by collapsing the acid sites of the catalyst. The recycling of the catalyst showed that there was no leaching of the metal as there was no drop in the conversion rate in the subsequent recycling reactions.
5. Conclusion In summary, three component Mannich-type reaction of aldehyde, amine, and ketone is efficiently catalyzed by yttria–zirconia based Lewis acid in aqueous CH3CN. The reaction works well with a wide range of structural variations in all the three components. The important feature of this methodology is the easy preparation of the catalyst and its reactivation (by calcination) after the reaction. Acknowledgement The authors are thankful to Dr M. K. Dongare of catalysis division of NCL, Pune for providing the catalysy and Dr. Ganesh Pandey, HOD, Division of Organic Chemistry for his support and encouragement. This is NCL communication No. 6708. References [1] S. Kobayashi, R. Matusubara, Y. Nakamura, H. Kitagawa, M. Sugiura, J. Am. Chem. Soc. 125 (2003) 2507. [2] S. Kobayashi, Curr. Opin. Chem. Biol. 4 (2000) 338. [3] K. Ishihara, M. Miyata, K. Hattori, T. Tada, H. Yamamoto, J. Am. Chem. Soc. 116 (1994) 10520. [4] K. Miura, K. Tamaki, T. Nakagawa, A. Hosomi, Angew. Chem. Int. Ed. Engl. 39 (2000) 1958. [5] M. Arend, B. Westermann, N. Risch, Angew. Chem. Int. Ed. Engl. 37 (1998) 1045. [6] S. Koboyashi, K. Manabe, Acc. Chem. Res 35 (2002) 209. [7] D.E. Bergbreiter, Chem. Rev. 201 (2002) 3345. [8] H. Ishitani, M. Ueno, S. Kabayashi, J. Am. Chem. Soc. 122 (2000) 8180. [9] H. Ishitani, S. Kobayashi, Org. Lett. 4 (2002) 3395. [10] B.C. Maity, V.G. Puranik, A. Sarkar, Synlett 3 (2002) 504. [11] T.-P. Loh, S.-L. Chen, Org. Lett. 21 (2002) 3647. [12] K. Manabe, Y. Mori, S. Koboyashi, Tetrahedron 57 (2001) 2537. [13] S. Iimura, D. Nobutou, K. Manabe, S. Kobayashi, Chem. Commun. (2003) 1644. and references therein. [14] T. Akiyama, J. Takaya, H. Kagoshima, Tetrahedron Lett. 42 (2001) 4025. [15] A.L. Joffe, T.M. Thomas, J.C. Adrian Jr., Tetrahedron Lett. 45 (2004) 5087. [16] G. Zhao, T. Jiang, H. Gao, B. Han, J. Huang, B. Sun, Green Chemistry 6 (2004) 75. [17] B. List, J. Am. Chem. Soc. 122 (2000) 9336. [18] A. Keshava raja, V.R. Hegde, B. Pandey, A.V. Ramaswamy, P. Kumar, T. Ravindranathan, Angew. Chem. Int. Ed. Engl. 34 (1995) 2143. [19] P. Kumar, R.K. Pandey, M.S. Bodas, S.P. Dagade, M.K. Dongare, A.V. Ramaswamy, J. Mol. Catal. A. Chem. 181 (2002) 207. and references therein. [20] B.S. Furniss, A.J. Hannaford, V. Rogeres, P.W.G. Smith, A.R. Tatchell (Eds.), Vogel’s Text book Practical Organic Chemistry, fourth ed., ELBS/Longman, London, 1978. [21] N. Mizuno, H. Fujii, H. Igarashi, M. Misono, J. Am. Chem. Soc. 114 (1992) 7151. [22] R. Cid, Gid, G. Pecchi, Appl. Catal. 14 (1985) 15. [23] M.J.F.M. Verhaak, A.J. Van Dillen, J.W. Geus, Appl. Catal. 105 (1993) 251.