b Department of Chemical Engineering, Jiuquan Vacational and Technical College, Jiuquan 735009, China;
c Gansu Engineering Laboratory of Applied Mycology, Hexi University, Zhangye 734000, China
Mannich reactions are very important carbon–carbon bondforming reactions in organic synthesis [1,2]. They provide b-amino carbonyl compounds, which are important synthetic intermediates for various pharmaceuticals and natural products [3,4]. The increasing popularity of the Mannich reaction has been fueled by the ubiquitous use of nitrogen containing compounds in drugs and natural products [5,6]. Therefore, the development of new synthetic methods leading to b-amino carbonyl compounds or their derivatives has attracted much attention. Recently, some modern versions of the Mannich reaction using performed electrophiles, such as imines, and stable nucleophiles, such as enolates, enol ethers, and enamines [7–15], have been developed. However, the preferred route is to use a one-pot, three-component strategy that gives a wide range of structural variations.
Recently, one-pot Mannich reactions of unmodified aldehydes, ketones, and amines have been promoted by a wide array of catalysts, such as ionic liquid , SDS–HCl [17,18], proline , GuHCl , CeCl3·7H2O , polymer-support sulfonic acid (PSSO3H) , H3PW12O40 , Lewis acids [24–29], silica-AlCl3 , silica sulfuric acid , or PEG-SO3H . However, most of these procedures have some drawbacks, such as harsh reaction conditions, tedious work-ups, or difficulties recovering, isolating and recycling the expensive, toxic catalysts. Although one-pot Mannich reactions can be carried out in the presence of H3PW12O40  in water, the catalysts cannot be recycled.
Ionic liquids (ILs) have been attracting significant attention as alternative solvents and catalysts for chemical reactions because of their negligible volatility, remarkable solubility, and potential recyclability [33–35]. In recent years, the use of heteropolyacidbased IL (HPA-IL) to catalyze organic reactions is an ongoing research area . Some HPA-IL composites have been reported and employed as catalysts for acid-catalyzed reactions [37–42]. Considering that ionic polymers containing IL units are potentially capable of ILs and polymers, such as high thermal stability, easy modification, corrosion resistance, and a variety of available structures [43,44], the catalytic stabilities of these catalysts need to be improved. Compared with imidazolium ILs, pyridinium ILs are generally more readily biodegradable .
Most recently, we have reported the preparation of sulfonated poly(4-vinylpyridine) heteropolyacid salts (Scheme 1) and used it as a catalyst for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones under ultrasonic irradiation (Scheme 2) . In continuation of our work to develop new catalysts for organic transformations [46– 48], here we report the synthesis of b-amino carbonyl compounds in the presence of sulfonated poly(4-vinylpyridine) heteropolyacid salts (Scheme 3).
|Scheme 2.The synthesis of 2,3-dihydroquinazolin-4(1H)-ones catalyzed by poly(VPyPS)-PW under sonication.|
2. Experimental 2.1. General
Melting points were determined on a Perkin-Elmer differential scanning calorimeter, and the temperature was uncorrected. The IR spectra were run on a Nicolet spectrometer (KBr). NMR spectra were recorded at 400 (1H) and 100 (13C) MHz, respectively, on a Varian Mercury plus-400 instrument using CDCl3 as solvent and TMS as the internal standard. Thermogravimetric analysis was carried out under nitrogen using a Shimadzu TGA-50 spectrometer. X-ray diffraction (XRD) images were obtained from a Bruker XRD D8 Advance instrument with Cu Ka radiation. All the solvents used were strictly dried according to standard operation.
2.2. General procedure for Mannich reaction
To the mixture of acetophenone (0.30 g, 2.0 mmol), 4-nitrobenzaldehyde (0.21 g, 2.0 mmol) and aniline (0.19 g, 2.0 mmol) in 6 mL of ethanol, poly(VPyPS)-PW (0.03 g) was added. The mixture was stirred at room temperature for the appropriate time indicated in Table 2 until the reaction was completed as monitored by TLC. The resulting mixture was filtered to recover the catalyst, and the filtrate was evaporated off the solvent to give the crude product. The analytical sample was obtained by recrystallization of crude product from ethanol and acetone (2:3). The separated catalyst was washed with cold ethanol, then dried at 60 8C under vacuum for 4 h. The recovered catalyst was directly used for the next run. The product was collected from the filtrate after cooling to room temperature and recrystallization from the ethanol to give compounds 4a–4m. The b-amino carbonyl compounds were characterized by the use of spectral data and comparison of their physical data with the literature. Spectral data for compound 4c: White solid; IR (KBr): n 3380, 1668; 1H NMR (CDCl3, 400 MHz): d 7.91 (d, 2H, J = 8.0 Hz, ArH), 7.57 (t, 1H, J = 8.8 Hz, ArH), 7.45 (t, 2H, J = 8.0 Hz, ArH), 7.37 (d, 2H, J = 8.8 Hz, ArH), 7.12 (t, 2H, J = 8.0 Hz, ArH), 6.85 (d, 2H, J = 8.8 Hz, ArH), 6.72 (t, 1H, J = 7.1 Hz, ArH), 6.63 (d, 2H, J = 7.6 Hz, ArH), 4.97 (t, 1H, J = 6.0 Hz, NCH), 3.78 (s, 3H, CH3O), 3.53 (d, 2H, J = 6.0 Hz, COCH2).
3. Results and discussion
In order to establish the optimal experimental conditions for the preparation of b-amino carbonyl compounds, the Mannich reaction between benzaldehyde (2.0 mmol), acetophenone (2.0 mmol) and aniline (2.0 mmol) as model substrates was carried out using poly(VPyPS)-PW as catalyst in various solvents. Several solvents were tested for the reaction, such as EtOH, MeCN, CH2Cl2, H2O and PhMe. The reaction hardly proceeded in CH2Cl2, H2O or PhMe. However, the reaction in EtOH afforded product in high selectivity with nearly complete conversion. It seemed that the solvents also played an important role in the Mannich reaction catalyzed by poly(VPyPS)-PW. Therefore, EtOH was selected as the reaction solvent in the following investigation (Table 1). The results show clearly that poly(VPyPS)-PW is an effective catalyst for this transformation, and in the absence of Poly(VPyPS)-PW the reaction did not take place, even after 24 h. Although a lower catalyst loading (0.01 g of poly(VPyPS)-PW) could be used to accomplish this reaction, 30 mg of poly(VPyPS)-PW was optimum in terms of reaction time and isolated yield.
Encouraged by this result, in order to build the generality of the reaction, a series of aldehydes, aromatic ketones, and aromatic amines were investigated under the optimized reaction conditions (Table 2). As expected, these reactions proceeded smoothly and the desired products were obtained in good to excellent yields. A variety of aromatic aldehydes with either electron-donating or electron-withdrawing groups were converted to b-amino carbonyl compounds in good to excellent yields (74–96%).
To show the efficiency of the sulfonated poly(4-vinylpyridine) heteropolyacid salts in comparison with previously reported procedures in the literature, Table 3 compares some of our results with polymer-supported sulfonic acid (PS-SO3H) , H3PW12O40 , silica-AlCl3 , silica sulfuric acid , and PEG-SO3H  with respect to reaction times and yields of obtained products. The results in Table 3 show that the condensation reaction carried out with poly(VPyPS)-PW requires shorter reaction time and higher yield.
The recovery and reuse of the catalyst is highly preferable for a greener process. Thus, the recyclability of poly(VPyPS)-PW was investigated by using acetophenone, benzaldehyde and aniline as model substrates. The catalyst was easily separated by filtration after the reaction and washed with cold ethanol, dried under vacuum and reused in a subsequent reaction. The yields remained unchanged even after the catalyst had been recycled six times (Table 4).
We developed a sulfonated poly(4-vinylpyridine) heteropolyacid salt catalyst and used it in a Mannich reaction between aldehydes, aromatic ketones, and aromatic amines to prepare bamino carbonyl compounds in excellent yields (up to 96%). Owing to the combination of SO3H functional groups, the polymeric framework of IL-cation and the large heteropolyanion, the Mannich reactions can be conducted effectively. In addition, the catalyst can be easily separated and reused six times without significant loss of activity. Besides the synthesis of b-amino carbonyl compounds, such an environmentally benign catalyst should find a wider application in various acid-catalyzed reactions, which is an ongoing project.
This work was financially supported by Key Laboratory of Hexi Corridor Resources Utilization of Gansu Universities (No. XZ1011), the President’s Funds of Hexi University (No. XZ-2009-9), Gansu Engineering Laboratory of Applied Mycology, and the National Science Foundation of China (No. 21262010).
|||M. Arend, B. Westermann, N. Risch, Modern variants of the Mannich reaction, Angew. Chem. Int. Ed. 37 (1998) 1044-1070.|
|||S. Kobayashi, H. Ishitani, Catalytic enantioselective addition to imines, Chem. Rev. 99 (1999) 1069-1094.|
|||R. Muller, H. Goesmann, H. Waldmann, N,N-Phthaloylamino acids as chiral auxiliaries in asymmetric Mannich-type reactions, Angew. Chem. Int. Ed. 38 (1999) 184-187.|
|||H. Bohme, M. Haake, in: E.C. Taylor (Ed.), Advances in Organic Chemistry, vol. 7, John Wiley and Sons, New York, 1976, p. 107.|
|||M. Suginome, L. Uehlin, M. Murakami, Aminoboranes as "compatible" iminium ion generators in aminative C-C bond formations, J. Am. Chem. Soc. 126 (2004) 13196-13197.|
|||W. Notz, F. Tanaka, S.I. Watanabe, et al., The direct organocatalytic asymmetric Mannich reaction: unmodified aldehydes as nucleophiles, J. Org. Chem. 68 (2003) 9624-9634.|
|||B.M. Trost, L.R. Terrell, A direct catalytic asymmetric Mannich-type reaction to syn-amino alcohols, J. Am. Chem. Soc. 125 (2003) 338-339.|
|||S. Matsunaga, N. Kumagai, S. Harada, M. Shibasaki, Anti-selective direct catalytic asymmetric Mannich-type reaction of hydroxyketone providing β-amino alcohols, J. Am. Chem. Soc. 125 (2003) 4712-4713.|
|||K. Juhl, N. Gathergood, K.A. Jørgensen, Catalytic asymmetric direct Mannich reactions of carbonyl compounds with a-imino esters, Angew. Chem. Int. Ed. 40 (2001) 2995-2997.|
|||B. List, The direct catalytic asymmetric three-component Mannich reaction, J. Am. Chem. Soc. 122 (2000) 9336-9337.|
|||B. List, P. Pojarliev, W.T. Biller, H.J. Martin, The proline-catalyzed direct asymmetric three-component Mannich reaction: scope, optimization, and application to the highly enantioselective synthesis of 1,2-amino alcohol, J. Am. Chem. Soc. 124 (2002) 827-833.|
|||A. Cordova, W. Notz, G. Zhong, J.M. Betancort, C.F. Barbas, A highly enantioselective amino acid-catalyzed route to functionalized α-amino acids, J. Am. Chem. Soc. 124 (2002) 1842-1943.|
|||S. Kobayashi, T. Hamada, K. Manabe, The catalytic asymmetric Mannich-type reactions in aqueous media, J. Am. Chem. Soc. 124 (2002) 5640-5641.|
|||Y. Hayashi, W. Tsuboi, I. Ashimine, et al., The direct and enantioselective, one-pot, three-component, cross-Mannich reaction of aldehydes, Angew. Chem. Int. Ed. 42 (2003) 3677-3680.|
|||A.G. Wenzel, E.N. Jacobsen, Asymmetric catalytic mannich reactions catalyzed by urea derivatives: enantioselective synthesis of b-aryl-β-amino acids, J. Am. Chem. Soc. 124 (2002) 12964-12965.|
|||S. Sahoo, T. Joseph, S.B. Halligudi, Mannich reaction in Bro¨nsted acidic ionic liquid: a facile synthesis of β-amino carbonyl compounds, J. Mol. Catal. A: Chem. 244 (2006) 179-182.|
|||T. Akiyama, K. Matsuda, K. Fuchibe, HCl-catalyzed stereoselective Mannich reaction in H2O-SDS system, Synlett (2005) 322-324.|
|||K. Matsuda, Y. Mori, S. Kobayashi, Three-component carbon-carbon bond-forming reactions catalyzed by a Brønsted acid-surfactant-combined catalyst in water, Tetrahedron 57 (2001) 2537-2544.|
|||M.L. Kantam, C.V. Rajasekhar, G. Gopikrishna, K.R. Reddy, B.M. Choudary, Proline catalyzed two-component, three-component and self-asymmetric Mannich reactions promoted by ultrasonic conditions, Tetrahedron Lett. 47 (2006) 5965-5967.|
|||M.M. Heravi, M. Zakeri, N. Mohammadi, Guanidine hydrochloride: an active and simple catalyst for Mannich type reaction in solvent-free condition, Chin. Chem. Lett. 22 (2011) 797-800.|
|||Y. Dai, B.D. Li, H.D. Quan, C.X. Liu, CeCl3·7H2O as an efficient catalyst for one-pot synthesis of β-amino ketones by three-component Mannich reaction, Chin. Chem. Lett. 21 (2010) 31-34.|
|||S. Iimura, D. Nobutou, K. Manabe, S. Kobayashi, Mannich-type reactions in water using a hydrophobic polymer-supported sulfonic acid catalyst, Chem. Commun. (2003) 1644-1645.|
|||N. Azizi, L. Torkiyan, M.R. Saidi, Highly efficient one-pot three-component Mannich reaction in water catalyzed by heteropoly acids, Org. Lett. 8 (2006) 2079-2082.|
|||R. Wang, B.G. Li, T.K. Huang, L. Shi, X.X. Lu, NbCl5-catalyzed one-pot Mannich-type reaction: three component synthesis of β-amino carbonyl compounds, Tetrahedron Lett. 48 (2007) 2071-2073.|
|||L.M. Wang, J.W. Han, J. Sheng, H. Tian, Z.Y. Fan, Rare earth perfluorooctanoate|
|||L.M. Wang, J.W. Han, J. Sheng, Z.Y. Fan, H. Tian, Yb(OTf)3 catalyzed Mannich reaction of acetophe-none with aromatic aldehydes and aromatic amines: three component one-pot synthesis of β-amino ketone derivatives, Chin. J. Org. Chem. 25 (2005) 591-594.|
|||Y.G. Wang, Y.Y. Yang, W.G. Shou, Synthesis of β-amino carbonyl compounds via a Zn(OTf)2-catalyzed cascade reaction of anilines with aromatic aldehydes and carbonyl compounds, Tetrahedron 62 (2006) 10079-11086.|
|||Y.G. Wang, Y.Y. Yang, W.G. Shou, An efficient synthesis of β-amino esters via Zn(OTf)2-catalyzed Mannich-type reaction, Tetrahedron Lett. 47 (2006) 1845- 1847.|
|||H. Li, H. Zeng, H. Shao, Bismuth (ⅡI) chloride-catalyzed one-pot Mannich reaction: three-component synthesis of β-amino carbonyl compounds, Tetrahedron Lett. 50 (2009) 6858-6860.|
|||Z. Li, X.L. Ma, J. Liu, et al., Silica-supported aluminum chloride: a recyclable and reusable catalyst for one-pot three-component Mannich-type reactions, J. Mol. Catal. A: Chem. 272 (2007) 132-135.|
|||H. Wu, Y. Shen, L. Fan, et al., Stereoselective synthesis of β-amino ketones via direct Mannich-type reaction catalyzed with silica sulfuric acid, Tetrahedron 63 (2007) 2404-2408.|
|||X.C. Wang, L.J. Zhang, Z. Zhang, Z.J. Quan, PEG-OSO3H as an efficient and recyclable catalyst for the synthesis of β-amino carbonyl compounds via the Mannich reaction in PEG-H2O, Chin. Chem. Lett. 23 (2012) 423-426.|
|||Q.H. Zhang, S.G. Zhang, Y.Q. Deng, Recent advances in ionic liquid catalysis, Green Chem. 13 (2011) 2619-2637.|
|||D. Chaturvedi, Recent developments on task specific ionic liquids, Curr. Org. Chem. 15 (2011) 1236-1248.|
|||J.P. Hallett, T. Welton, Room-temperature ionic liquids: solvents for synthesis and catalysis, Chem. Rev. 111 (2011) 3508-3576.|
|||L. Gharnati, O. Walter, U. Arnold, M. Döring, Guanidinium-based phosphotungstates and ionic liquids as catalysts and solvents for the epoxidation of olefins with hydrogen peroxide, Eur. J. Inorg. Chem. (2011) 2756-2762.|
|||H. Li, Y.X. Qiao, L. Hua, et al., Imidazolium polyoxometalate: an ionic liquid catalyst for esterification and oxidative esterification, Chem. Cat. Chem. 2 (2010) 1165-1170.|
|||Y.X. Qiao, Z.S. Hou, H. Li, et al., Polyoxometalate-based protic alkylimidazolium salts as reaction-induced phase-separation catalysts for olefin epoxidation, Green Chem. 11 (2009) 1955-1960.|
|||Y. Leng, J. Wang, D. Zhu, et al., Heteropolyanion-based ionic liquids: reactioninduced self-separation catalysts for esterification, Angew. Chem. Int. Ed. 48 (2009) 168-171.|
|||Y.Leng,J.Wang,D.Zhu,Y.Wu,P.Zhao,Sulfonatedorganicheteropolyacidsalts:recyclable green solid catalysts for esterifications, J.Mol. Catal. A: Chem. 313 (2009) 1-6.|
|||W. Zhang, Y. Leng, D. Zhu, Y. Wu, J. Wang, Phosphotungstic acid salt of triphenyl( 3-sulfopropyl)phosphonium: an efficient and reusable solid catalyst for esterification, Catal. Commun. 11 (2009) 151-154.|
|||Y. Leng, P.P. Jiang, J. Wang, A novel Brønsted acidic heteropolyanion-based polymeric hybrid catalyst for esterification, Catal. Commun. 25 (2012) 41-44.|
|||J. Yuan, M. Antonietti, Poly(ionic liquid)s: polymers expanding classical property profiles, Polymer 52 (2011) 1469-1482.|
|||Z.J. Xu, H. Wan, J.M. Miao, M.J. Han, C. Yang, G.F. Guan, Reusable and efficient polystyrene-supported acidic ionic liquid catalyst for esterifications, J. Mol. Catal. A: Chem. 332 (2010) 152-157.|
|||K.M. Docherty, J.K. Dixon, C.F. Kulpa, Biodegradability of imidazolium and pyridinium ionic liquids by an activated sludge microbial community, Biodegradation 18 (2007) 481-493.|
|||J.K. Wang, Y.X. Zong, R.G. Fu, Y.Y. Niu, G.R. Yue, Z.J. Quan, X.C. Wang, Y. Pan, Poly(4- vinylpyridine) supported acidic ionic liquid: a novel solid catalyst for the efficient synthesis of 2,3-dihydroquinazolin-4(1H)-ones under ultrasonic irradiation, Ultrason. Sonochem. 21 (2014) 29-34.|
|||Y.X. Zong, Y. Zhao, W.C. Luo, X.H. Yu, J.K. Wang, Y. Pan, Highly efficient synthesis of 2,3-dihydroquinazolin-4(1H)-ones catalyzed by heteropoly acids in water, Chin. Chem. Lett. 21 (2010) 778-781.|
|||Y.X. Zong, J.K. Wang, Y.Y. Niu, Z.L. Li, Z.E. Song, Z.J. Quan, X.C. Wang, G.R. Yue, Y. Pan, PEG-SO3H as an efficient and reusable catalyst for chemoselective synthesis of 1,1-diacetates, Chin. Chem. Lett. 24 (2013) 140-142.|