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Aldol condensations of aldehydes and ketones catalyzed by rare earth(III) perfluorooctane sulfonates in fluorous solvents
Journal of Fluorine Chemistry 126 (2005) 1553–1558 www.elsevier.com/locate/fluor
Aldol condensations of aldehydes and ketones catalyzed by rare earth(III) perfluorooctane sulfonates in fluorous solvents Wen-Bin Yi, Chun Cai * Chemical Engineering College, Nanjing University of Science and Technology, Nanjing 210094, China Received 8 September 2005; accepted 8 September 2005 Available online 20 October 2005
Abstract Rare earth(III) perfluorooctane sulfonates (RE(OPf)3) catalyze the efficient aldol condensation of different ketones with various aromatic aldehydes in fluorous solvents without the occurrence of any self-condensations. By simple separation of the fluorous phase containing only catalyst, reaction can be repeated several times. # 2005 Elsevier B.V. All rights reserved. Keywords: Aldol condensations; Fluorous biphasic catalysis; Rare earth(III) perfluorooctanesulfonates; Perfluorocarbon
1. Introduction Aldol condensation reactions are important synthetic reactions and in classical methods, they were performed in the presence of strong acids or bases [1]. In order to do these reactions under neutral conditions, some metal ions are used as catalyst or reagent [2]. For example, the use of different complexes of metal(II) ions, such as Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) with different ligands have been used for aldol-condensations [2a]. Recently, a new kind of Lewis acids of rare earth(III) perfluorooctane sulfonates (RE(OSO2C8F17)3, RE(OPf)3, RE = Sc, Y, La–Lu) was of special interest [3–5]. The characteristic features of the catalyst include low hygroscopicity, ease of handling, robustness for the recycling using and high solubility in fluorous solvent [4]. On the other hand, perfluorocarbon solvents, especially perfluoroalkanes have some unique properties which make them attractive alternatives for conventional organic solvents [6]. The compounds functionalized with perfluorinated groups often dissolve preferentially in fluorous solvents and this property can be used to extract fluorous components from reaction mixtures [7]. Aldol condensations of aldehydes and ketones catalyzed by rare earth(III) trifluoromethanesulfonates (RE(OSO2CF3)3, RE(OTf)3) were reported [8]. However,
* Corresponding author. Fax: +86 25 84315030. E-mail address: [email protected] (C. Cai). 0022-1139/$ – see front matter # 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.jfluchem.2005.09.004
reusing of these catalysts required tedious work up procedures such as filtration, purification and drying. Therefore, we believe that the application of fluorous phase separation techniques in catalysis can be used to the aldol condensation catalyzed by RE(OPf)3 which has stronger Lewis acidity than RE(OTf)3. In this paper, a green process of aldol condensations of aldehydes and ketones catalyzed by rare earth(III) perfluorooctane sulfonates in fluorous solvents was studied. 2. Results and discussion Due to the importance of methylene structural unit which are found in many naturally occurring compounds and antibiotics and the use of a,a0 -bis(substituted) benzylidene cycloalkanones as precursors for synthesis of bioactive pyrimidine derivatives, condensation of cyclopentanone and cyclohexanone with aldehydes and ketones were of special interest [2f]. Thus, we studied the cross-condensations of cyclopentanone and cyclohexanone with different aromatic aldehydes such as, benzaldehyde, p-chlorobenzaldehyde, p-nitrobenzaldehyde, pmethylbenzaldehyde, p-methoxybenz-aldehyde and cinnamaldehyde. Firstly, The reaction of cyclohexanone with benzaldehyde was adopted for the evaluation of catalysts (Scheme 1). The results are summarized in Table 1. Among these catalysts, Sc(OPf)3 and Yb(OPf)3 are the most efficient catalysts for the condensation. This would be ascribed to the higher Lewis acidity of Sc(OPf)3 and Yb(OPf)3 than those of other RE(OPf)3 [9]. The control experiment elucidates that no product of cross-
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Scheme 1. Scheme 2.
condensations could be obtained in the absence of catalyst and fluorous solvent. In addition, we found that a catalyst loading of only 0.4 mol% was required when using fluorous phase technology. Next, the effect of fluorous solvents such as, perfluorohexane (C6F14), perfluoromethylcyclohexane (C7F14), perfluorotoluene (C7F8), perfluorooctane (C8F18), perfluorooctyl bromide (C8F17Br) and perfluorodecalin (C10F18, cis and trans-mixture) was examined for the condensations (Table 1, entries 16–21). The results showed that yields of the desired products in perfluorooctane (C8F18) and perfluorooctyl bromide (C8F17Br) were lower than other solvents. The fluorous solvents perfluorohexane (C6F14) and perfluorotoluene (C7F8) are in fact miscible with reaction substrates such as cyclohexanone at room temperature. Thus, it is impossible to recover fluorous phase by phase-separation. At the same time, we found that during repeated condensation reactions the loss of fluorous solvent is very serious when using perfluoromethylcyclohexane (C7F14) as a fluorous solvent because it is very volatile (bp 76 8C). Therefore, perfluorodecalin (C10F18, cis and transmixture) is the best fluorous solvent for the condensation. Heptadecafluorooctane-sulfonic acid (C8F17SO3H, PfOH) itself can promote the reaction, but it was found to be less effective than RE(OPf)3.
Table 1 Condensation of cyclohexanone with benzaldehydea Entry
Catalyst
Fluorous solvent
Yield (%)b
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Sc(OPf)3 Y(OPf)3 La(OPf)3 Ce(OPf)3 Pr(OPf)3 Nd(OPf)3 Sm(OPf)3 Eu(OPf)3 Gd(OPf)3 Tb(OPf)3 Dy(OPf)3 Ho(OPf)3 Er(OPf)3 Tm(OPf)3 Lu(OPf)3 Yb(OPf)3 Yb(OPf)3 Yb(OPf)3 Yb(OPf)3 Yb(OPf)3 Yb(OPf)3 PfOH
C10F18 c C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 CF3(CF2)4CF3 C6F5CF3 C6F13CF3 CF3(CF2)6CF3 CF3(CF2)6CF2Br C10F18
96 78 69 80 60 88 73 66 77 72 84 86 90 79 78 95 89 97 96 82 81 53
a b c
The mole ratio of cyclohexane to benzaldehyde in all cases is 5:3. Isolated yields based on the benzaldehyde. .
Table 2 Condensation of cyclopentanone and cyclohexanone with various aromatic aldehydesa Entry
N
Ar
Temperature (8C)
Time (h)
Yield (%) b
1 2 3 4 5 6 7 8 9 10 11
1 1 1 1 1 1 0 0 0 0 0
4-ClPh 4-CH3Ph 4-CH3OPh 4-NO2Ph Cinnamyl Furfuryl Ph 4-CH3OPh 4-NO2Ph Cinnamyl Furfuryl
120 120 120 120 120 120 120 120 120 120 120
12 4 18 24 16 24 8 18 24 8 24
95 92 94 97 96 89 92 91 95 93 86
a b
The mole ratio of ketone to aromatic aldehyde in all cases is 5:3. Isolated yields based on the benzaldehyde.
In order to seek out a practical, useful aldol condensation process, we decided to use the relatively cheap and similarly active catalyst Yb(OPf)3 and perfluorodecalin (C10F18, cis and trans-mixture) as a fluorous solvent for condensations of cyclopentanone and cyclohexanone with various aromatic aldehydes (Scheme 2). The results are shown in Table 2. The reactions were finished within 4–24 h and excellent yields (86– 97%) of a,a0 -bis(substituted) benzylidene cyclopentanones and cyclohexanones were obtained, regardless of the kind of substituent group on benzaldehyde. Under the conditions described in Table 2, Yb(OPf)3 catalyzed the efficient cross aldol condensations without the occurrence of any selfcondensations. In order to ascertain the scope and limitation of this catalyzed condensation, the use of the catalytic systems was extend to condensation of aliphatic and aromatic ketones with various aldehydes (Scheme 3, Table 3). The reaction products were isolated and identified as a,b-unsaturated ketones, and no side reactions were observed. Based on 1H NMR and GC–MS data, the reaction was found to give E-stereoisomer as sole product. The purity of the products thus obtained was consistently high, probably because the perflates-catalyzed reactions took place under neutral conditions. In general, reactions between aromatic aldehydes and ketones gave good results, but not those of aliphatic compounds. The condensations of p-substituted benzaldehyde with p-substituted acetophenones yielded the corresponding chalcones and the
Scheme 3.
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Table 3 Condensation of acyclic ketones with various aromatic aldehydesa Entry
R1
R2
R3
Temperature (8C)
Time (h)
Yield (%) b
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Ph 4-CH3OPh 4-NO2Ph Ph Ph Ph Ph Ph Ph CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3
H H H H H H H H H H H CH3 CH3 C2H5 C2H5 H H CH3 CH3
Ph Ph Ph 4-ClPh 4-CH3Ph 4-CH3OPh 4-NO2Ph Cinnamyl (CH3)2CH Ph 4-CH3OPh Ph 4-CH3OPh Ph 4-CH3OPh C2H5 C3H7 C2H5 C3H7
120 120 120 120 120 120 120 120 80 80 80 80 80 80 80 60 80 60 80
24 24 24 24 24 24 24 32 72 48 48 48 48 48 48 72 72 72 72
85 69 95 89 76 65 96 41 32 77 75 58 51 46 37 7 4 6 3
a b
The mole ratio of ketone to aromatic aldehyde in all cases is 5:3. Isolated yields based on the benzaldehyde.
product yields were remarkably affected by the subsitituent groups of either aldehydes of ketones: reactants having electron-withdrawing substituents gave high yields and those having electron-donating ones gave low yields. The reactions of various aromatic aldehydes with acetone gave corresponding a,b-unsaturated ketones in good yields. It was known that the base-catalyzed reactions of 2-butanone with benzaldehyde gave preferentially the condensation product at C1 of ketone, while the acid catalyzed reaction occurred preferentially at C3. The obtained results from condensation of 2-butanone and 2pentanone with different aromatic aldehydes showed excellent regioselectivity with the occurrence of condensation from C3. The catalyst Yb(OPf)3 system appeared to show no catalytic activity for the condensation of the aliphatic ketones such as acetone and 2-butanone with the aliphatic aldehydes, propanal and pentanal. Attempts were made to recycle the catalytic system. The condensations of cyclohexanone and acetophenone with benzaldehyde under the conditions as mentioned above were run for five consecutive cycles, respectively, furnishing the corresponding a,a0 -bis(substituted) benzylidene cyclopentanones with 95, 95, 93, 92, 92% isolated yields and chalcone with 85, 84, 85, 84, 83% isolated yields. The robustness of the catalyst for recycling using may partly be attributed to the water-repellent nature of the perfluoroalkane chain ‘‘(–CF2– CF2–)n’’ of RE(OPf)3 which refuses the approach of water or acid molecules to the central metal cation, thus maintaining its high Lewis acidity [9]. When the reaction was finished, the reaction mixture was cooled to room temperature. The fluorous phase with RE(OPf)3 catalysts can separate from the organic layer return to the bottom layer. Based on GC– MS data, no loss of fluorous solvent to the organic phase can be detected. The separated fluorous phase containing only catalyst
could be reused for the next reaction without any treatment, and this workup procedure of recycling was accomplished by simple phase-separation. In conclusion, RE(OPf)3 are demonstrated to be new and highly effective catalysts for condensations of aromatic aldehyhes and ketones in fluorous solvents. By simple separation of the fluorous phase containing only catalyst, reaction can be repeated several times. The simple procedures as well as easy recovery and reuse of this novel catalytic system are expected to contribute to the development of more benign aldol condensation. 3. Experimental 3.1. General MPs were obtained with Shimadzu DSC-50 thermal analyzer. IR spectra were recorded on a Bumem MB154S infrared analyzer. 1H NMR spectra were measured on Bruke Advance RX300. Mass spectra were recorded with a Saturn 2000GC/MS instrument. Inductively coupled plasma (ICP) spectra were measured on Ultima2C apparatus. Elemental analyses were performed on a Yanagimoto MT3CHN corder. Commercially available reagents were used without further purification. 3.2. Typical procedure for preparation of RE(OPf)3 RE(OPf)3 was prepared according to the literatures [4] (Method A). The mixture of PfOH solution (aq) and YbCl36H2O solution (aq) was stirred at room temperature (Method B). The mixture of PfOH solution (aq) and Yb2O3 powder was stirred at boiling. In both methods, the resulting gelatin-like solid was collected, washed and dried at 150 8C in vacuo to give a white
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solid, which does not have a clear melting point up to 500 8C, but shrinks around 380 8C and 450 8C. IR (KBr) n (cm1) 1237 (CF3), 1152 (CF2), 1081 (SO2), 1059 (SO2), 747 (S–O) and 652 (C–S). ICP: Calcd. for C24O9F51S3Yb: Yb, 10.30%. Found: Yb, 9.88%. Anal. Calcd. for C24O9F51S3YbH2O: C, 17.21%; H, 0.10%. Found: C, 17.03%; H, 0.18%. 3.3. Typical procedure for condensation of aldehydes with ketones Benzaldehyde (1.2 ml, 12 mmol) was slowly added into a mixture of Yb(OPf)3 (80 mg, 0.048 mmol), cyclohexone (2.1 ml, 20 mmol) and perfluorodecalin (C10F18, cis and trans-mixture, 1.5 ml). The mixture was stirred at 120 8C for 12 h. Then, the fluorous layer on the bottom was separated for the next condensation. The reaction mixture (organic phase) was poured into cold ethanol (20 ml) and stirred for 5 min and filtered. The crystalline product was further washed subsequently with water (10 ml), 10% NaHCO3 solution (10 ml) and water (10 ml 2), cold ethanol (10 ml) and dried to give the product 2,6-dibenzylidenecyclohexanone (1.56 g, 95%). 2,6-Dibenzylidenecyclohexanone. A yellow solid; mp 116– 118 8C (lit2e 116–117 8C). IR (KBr) n 3020, 2924, 1657, 1604, 1570, 1271, 1142, 770, 692 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.76–1.87 (m, 2H), 2.95 (t, J = 6.4 Hz, 4H), 7.30–7.48 (m, 10H), 7.80 (s, 2H). MS (EI) m/z 273 (M+). 2,6-Di(p-chlorobenzylidene)cyclohexanone. A brown solid; mp 149–151 8C (lit2f 147–148 8C). IR (KBr) n 2930, 1660, 1606, 1576, 1262, 828 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.76–1.84 (m, 2H), 2.90 (t, J = 6.0 Hz, 4H), 7.36–7.43 (m, 8H), 7.73 (s, 2H). MS (EI) m/z 346 (M+ + 4), 344 (M+ + 2), 342 (M+). 2,6-Di(p-methylbenzylidene)cyclohexanone. A yellowish solid; mp 170–171 8C (lit2f 170 8C). IR (KBr) n 2980, 2944, 1666, 1600, 1560, 1268, 1140, 760, 698 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.78–1.86 (m, 2H), 2.30 (s, 6H), 2.92 (t, J = 6.2 Hz, 4H), 7.22–7.38 (m, 8H), 7.76 (s, 2H). MS (EI) m/z 301 (M+). 2,6-Di(p-methoxybenzylidene)cyclohexanone. A yellow solid; mp 203–204 8C (lit2e 203–204 8C). IR (KBr) n 3020, 2924, 1657, 1604, 1570, 1271, 1142, 770, 692 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.80–1.83 (m, 2H), 2.94 (t, J = 6.0 Hz, 4H), 3.86 (s, 6H), 6.94–7.40 (m, 8H), 7.77 (s, 2H). MS (EI) m/z 333 (M+). 2,6-Di(p-nitrobenzylidene)cyclohexanone. A russety solid; mp 158–160 8C (lit2e 159 8C). IR (KBr) n 3082, 2925, 1663, 1606, 1576, 1525, 1346, 807 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.84–1.90 (m, 2H), 2.97 (t, J = 5.6 Hz, 4H), 7.60–8.22 (m, 8H), 8.32 (s, 2H). MS (EI) m/z 363 (M+). 2,6-Dicinnamylidenecyclohexanone. A yellowish solid; mp 179 8C (lit2e 180 8C). IR (KBr) n 3028, 2920, 1653, 1610, 1540, 1180,737, 690 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.96–2.16 (m, 2H), 2.86 (t, J = 6.4 Hz, 4H), 6.60 (d, J = 16.2 Hz, 2H), 6.83 (d, J = 16.2 Hz, 2H), 6.86–7.42 (m, 10H), 7.72 (s, 2H). MS (EI) m/z 325 (M+). 2,6-Difurfurylidenecyclohexanone. A purple solid; mp 140– 142 8C (lit2e 140–141 8C). IR (KBr) n 3149, 2940, 1643, 1590,
1546, 1278, 1147, 1010, 764 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.16–2.54 (m, 2H), 2.95 (d, 4H), 6.20–7.72 (m, 8H). MS (EI) m/z 253 (M+). 2,6-Dibenzylidenecyclopentanone. A brown solid; mp 188 8C (lit2e 188–189 8C). IR (KBr) n 3100, 2926, 1654, 1598, 1460,1260, 760, 674 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.76 (t, 4H), 7.26–7.38 (m, 10H), 7.68 (s, 2H). MS (EI) m/z 259 (M+). 2,6-Di(p-methoxybenzylidene)cyclopentanone. A green solid; mp 211–212 8C (lit2e 210–211 8C). IR (KBr) n 2962, 2841, 1649, 1595, 1506, 1253, 1020, 834 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 3.09 (t, 4H), 3.86 (s, 6H), 6.96–7.56 (m, 8H), 7.58 (s, 2H). MS (EI) m/z 319 (M+) 2,6-Di(p-nitrobenzylidene)cyclopentanone. A russety solid; mp 230–231 8C (lit2e 230–231 8C). IR (KBr) n 3105, 2847, 1706, 1605, 1521, 1344, 816 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 3.07 (t, 4H), 7.62–8.12 (m, 8H), 8.27 (s, 2H). MS (EI) m/z 349 (M+). 2,6-Dicinnamylidenecyclopentanone. A purple solid; mp 223–224 8C (lit2e 222–224 8C). IR (KBr) n 3024, 2925, 1698, 1625, 1598, 1447, 690 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.86 (m, 4H), 6.70 (d, J = 16.2 Hz, 2H), 6.76 (d, J = 16.2 Hz, 2H), 6.81–7.70 (m, 10H), 7.72 (s, 2H). MS (EI) m/ z 311 (M+). 2,6-Difurfurylidenecyclopentanone. A russety solid; mp 161 8C (lit2e 160–162 8C). IR (KBr) n 3130, 2931, 1683, 1625, 1600, 1287, 1240, 754 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.98 (m, 4H), 2.95 (d, 4H), 6.30–7.62 (m, 8H). MS (EI) m/z 239 (M+). Chalcone. A yellowish solid; mp 55–57 8C (lit2b 57–58 8C). IR (KBr) n 3230, 2934, 1830, 1725, 1650, 1287, 754, 685 cm1. 1 H NMR (300 MHz, TMS, CDCl3) d 6.12 (d, J = 16.0 Hz, 1H), 7.26 (d, J = 16.0 Hz, 1H), 7.10–7.32 (m, 5H), 7.42–7.92 (m, 5H). MS (EI) m/z 207 (M+). 40 -Methoxychalcone. A russety solid; mp 109–110 8C (lit2b 109–110 8C). IR (KBr) n 3200, 2886, 1830, 1725, 1660, 1212, 854, 734 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 3.78 (s, 3H), 6.10 (d, J = 16.0 Hz, 1H), 7.22 (d, J = 16.0 Hz, 1H), 7.12– 7.62 (m, 9H). MS (EI) m/z 238 (M+). 40 -Nitrochalcone. A yellow solid; mp 151–153 8C (lit2b 151– 152 8C). IR (KBr) n 3010, 2896, 1705, 1680, 1643, 1470, 921, 845 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 6.32 (d, J = 16.1 Hz, 1H), 7.36 (d, J = 16.1 Hz, 1H), 7.15–7.36 (m, 5H), 7.52–8.26 (m, 4H). MS (EI) m/z 253 (M+). 4-Chlorochalcone. A yellow solid; mp 114–115 8C (lit2b 114–117 8C). IR (KBr) n 3086, 2910, 1780, 1712, 1650, 1207, 914, 746 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 6.20 (d, J = 16.0 Hz, 1H), 7.12 (d, J = 16.0 Hz, 1H), 6.22 (d, 2H), 7.10– 7.32 (m, 4H), 7.38–8.01 (m, 5H). MS (EI) m/z 244 (M+ + 2), 242 (M+). 4-Methylchalcone. A yellowish solid; mp 98–99 8C (lit2b 97– 98 8C). IR (KBr) n 3213, 2914, 1760, 1698, 1650, 1090, 942, 850, 718 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.33 (s, 3H), 6.01 (d, J = 16.4 Hz, 1H), 7.02 (d, J = 16.4 Hz, 1H), 7.01–7.32 (m, 4H), 7.36–7.82 (m, 5H). MS (EI) m/z 221 (M+). 4-Methoxychalcone. A russety solid; mp 75–76 8C (lit2b 75– 77 8C). IR (KBr) n 3302, 2986, 1830, 1725, 1660, 1187, 934,
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820 cm1. 1H NMR (300 MHz, TMS, CDCl3) n 3.73 (s, 3H), 5.93 (d, J = 16.0 Hz, 1H), 6.88 (d, J = 16.0 Hz, 1H), 6.92–7.19 (m, 4H), 7.32–7.99 (m, 5H). MS (EI) m/z 238 (M+). 4-Nitrochalcone. A brown solid; mp 158–160 8C (lit2b 158– 160 8C). IR (KBr) n 3236, 2910, 1870, 1675, 1660, 1470, 918, 840 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 6.34 (d, J = 16.1 Hz, 1H), 7.39 (d, J = 16.1 Hz, 1H), 7.35–7.66 (m, 3H), 7.72–8.34 (m, 4H). MS (EI) m/z 252 (M+). Cinnamylideneacetophenone. A yellow solid; mp 103– 104 8C (lit2a 104–105 8C). IR (KBr) n 3112, 3001, 2950, 1875, 1746, 1634, 1180, 940, 829 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 6.28 (d, J = 15.9 Hz, 1H), 7.12 (d, J = 15.9 Hz, 1H), 7.05–7.24 (m, 5H), 6.84 (d, J = 15.4 Hz, 1H), 7.76 (d, J = 15.4 Hz, 1H), 7.45–7.83 (m, 5H). MS (EI) m/z 233 (M+). 1-Phenyl-4-methyl-2-penten-1-one. A yellowish liquid (lit2b); IR (CHCl3) n 1780, 1674, 1652, 1480, 927, 840, 762 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.15 (d, 6H), 1.70 (m, 1H), 6.08 (t, J = 15.5 Hz, 1H), 6.76 (d, J = 15.5 Hz, 1H), 7.32–7.86 (m, 5H). MS (EI) m/z 173 (M+). Benzylideneacetone. A yellowish solid; mp 40–41 8C (lit2b 41–42 8C). IR (KBr) n 3108, 2960, 1835, 1720, 1664, 1180, 943, 817 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.39 (s, 3H), 6.65 (d, J = 16.5 Hz, 1H), 7.45 (d, J = 16.5 Hz, 1H), 7.35– 7.72 (m, 5H). MS (EI) m/z 147 (M+). 4-Methoxybenzylideneacetone. A yellowish solid; mp 44– 45 8C (lit2b 44–46 8C). IR (KBr) n 3202, 2946, 1780, 1724, 1589, 1182, 920, 826, 764 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.26 (s, 3H), 3.82 (s, 3H), 6.50 (d, J = 16.0 Hz, 1H), 7.45 (d, J = 16.0 Hz, 1H), 7.10–7.32 (m, 4H). MS (EI) m/z 178 (M+). 3-Benzylidene-2-butanone. A yellowish liquid (lit2f); IR (CHCl3) n 3026, 2870, 1765, 1674, 1652, 1487, 927, 834 cm1. 1 H NMR (300 MHz, TMS, CDCl3) d 2.01 (d, 3H), 2.40 (s, 3H), 7.18–7.26 (m, 5H), 7.35 (s, 1H). MS (EI) m/z 159 (M+). 3-(2-Methoxybenzylidene)-2-butanone. A yellowish liquid (lit2f); IR (CHCl3) n 3129, 2976, 1763, 1660, 1486, 937, 835, 762 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.02 (d, 3H), 2.37 (s, 3H), 3.82 (s, 3H), 6.83–7.02 (m, 4H), 7.36 (s, 1H). MS (EI) m/z 190 (M+). 3-Benzylidene-2-pentanone. A yellowish liquid (lit2f); IR (CHCl3) n 3039, 2862, 1760, 1656, 1482, 923, 846, 757 cm1. 1 H NMR (300 MHz, TMS, CDCl3) d 1.86–2.46 (m, 5H), 2.40 (s, 3H), 7.12–7.22 (m, 5H), 7.40 (s, 1H). MS (EI) m/z 173(M+). 3-(4-Methoxybenzylidene)-2-pentanone. A yellowish liquid (lit2f); IR (CHCl3) n 3124, 2975, 1756, 1650, 1475, 903, 842, 748 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.84–2.44 (m, 5H), 2.38 (s, 3H), 3.79 (s, 3H), 6.86–7.13 (m, 4H), 7.40 (s, 1H). MS (EI) m/z 204 (M+). 3-Hexen-2-one. A colorless liquid (lit2b); IR (CHCl3) n 1770, 1653, 1472, 1312, 920, 832, 756 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.12 (t, 3H), 1.96 (m, 2H), 2.36 (s, 3H), 6.27 (m, J = 15.9 Hz, 1H), 7.12 (d, J = 15.9 Hz, 1H). MS (EI) m/z 97 (M+). 3-Hepten-2-one. A colorless liquid (lit2b); IR (CHCl3) n 1782, 1624, 1489, 1310, 912, 796, 724 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 0.96–1.37 (m, 5H), 1.92 (m, 2H),
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2.30 (s, 3H), 6.18 (m, J = 15.9 Hz, 1H), 7.16 (d, J = 15.9 Hz, 1H). MS (EI) m/z 111 (M+). 3-Methyl-3-hexen-2-one. A colorless liquid (lit2b); IR (CHCl3) n 1789, 1641, 1601, 1472, 1319, 1178, 920, 820, 783 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.04 (t, 3H), 1.93 (s, 3H), 2.04 (m, 2H), 2.35 (s, 3H), 6.5 (m, 2H). MS (EI) m/ z 111 (M+). 3-Methyl-3-hepten-2-one. A colorless liquid (lit2b); IR (CHCl3) n 1802, 1765, 1641, 1439, 1310, 1238, 918, 823, 763 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 0.92–1.41 (m, 5H), 1.87 (s, 3H), 1.96 (m, 2H), 2.28 (s, 3H), 6.52 (m, H). MS (EI) m/z 125 (M+). Acknowledgements We thank the National Defence Committee of Science and Technology (40406020103) for financial support. We also thank the Zhen-Ya Rare Earth Co. Ltd. for providing several kinds of rare earth oxides. References [1] (a) A.T. Nielsen, W.J. Houlihan, Org. React. 16 (1968) 1; (b) R.L. Reeves, in: S. Patai (Ed.), Chemistry of Carbonyl Group, Wiley/ Interscience, New York, 1966, pp. 580–593. [2] (a) K. Irie, K. Watanabe, Bull. Chem. Soc. Jpn. 53 (1980) 1366–1371; (b) K. Watanabe, A. Imazawa, Bull. Chem. Soc. Jpn. 55 (1982) 3208– 3211; (c) T. Nakamo, S. Irifune, S. Umano, A. Inada, Y. Ishii, M. Ogawa, J. Org. Chem. 52 (1987) 2239–2244; (d) Y. Yoshida, R. Hayashi, H. Sumihara, Y. Tanabe, Tetrahedron Lett. 38 (1997) 8727–8730; (e) M. Zheng, L. Wang, J. Shao, Q. Zhong, Synth. Commun. 27 (1997) 351–354; (f) N. Iranpoor, F. Kazemi, Tetrahedron 54 (1998) 9475–9480; (g) Y. Zheng, F.T.T. Ng, G.L. Rempel, Ind. Eng. Chem. Res. 40 (2001) 5342–5349; (h) R. Uma, M. Davies, C. Crevisy, R. Gree, Tetrahedron Lett. 42 (2001) 3069–3072; (i) D. Reardon, J. Guan, S. Gambarotta, G.P.A. Yap, D.R. Wilson, Organometallics 21 (2002) 4390–4397; (j) M. Sasidharan, R. Kumar, J. Catal. 220 (2003) 326–332; (k) A. Yanagisawa, T. Sekiguchi, Tetrahedron Lett. 44 (2003) 7163– 7166; (l) D. Mendez, E. Klimova, T. Klimova, L. Fernando, S. Hernondez, J. Organometall. Chem. 679 (2003) 10–13; (m) J. Mlynarski, M. Mitura, Tetrahedron Lett. 45 (2004) 7549–7552; (n) A. Clerici, N. Pastori, O. Porta, J. Org. Chem. 70 (2005) 4174– 4176. [3] (a) S. Kobayashi, I. Hachiya, T. Takahori, M. Araki, M. Ishitani, Tetrahedron Lett. 33 (1992) 6815–6818; (b) S. Kobayashi, H. Ishitani, I. Hachiya, M. Araki, Tetrahedron 50 (1994) 11623–11636; (c) K. Manabe, H. Oyamada, K. Sugita, S. Kobayashi, J. Org. Chem. 64 (1999) 8054–8057; (d) T. Kitazume, H. Nakano, Green Chem. 3 (1999) 179–181; (e) S. Kobayashi, A. Kawada, S. Mitamura, J. Matsuo, T. Suchiya, Bull. Chem. Soc. Jpn. 73 (2000) 2325–2333; (f) S. Kobayashi, I. Komoto, J. Matsuo, Adv. Synth. Catal. 343 (2001) 71– 74; (g) M. Shi, S.-C. Cui, Chem. Commun. 9 (2002) 994–995. [4] T. Hanamoto, Y. Sugimoto, Y.Z. Jin, J. Inanaga, Bull. Chem. Soc. Jpn. 70 (1997) 1421–1426. [5] M. Shi, S.-C. Cui, J. Fluorine Chem. 116 (2002) 143–147.
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[6] (a) D.W. Zhu, Synthesis 10 (1993) 953–954; (b) E.D. Wolf, G.V. Koten, B. Deelman, J. Chem. Soc. Rev. 28 (1999) 37– 41. [7] (a) I.T. Horvath, J. Rabai, Science 266 (1994) 72–75; (b) R.P. Huhges, H.A. Trujillo, Organometllics 15 (1996) 286–294; (c) G. Pozzi, F. Montanari, S. Quici, Chem. Commun. 1 (1997) 69–70; (d) R.H. Fish, Chem. Eur. J. 5 (1999) 1677–1680; (e) J.J.J. Juliette, I.T. Horvath, J.A. Gladysz, Angew. Chem. Int. Ed. Engl. 36 (1997) 1610–1612; (f) J. Otera, A. Orita, Angew. Chem. Int. Ed. Engl. 40 (2001) 3670– 3674;
(g) Y. Nakamura, S. Takeuchi, K. Okumura, O. Yoshiaki, P.C. Dennis, Tetrahedron 58 (2002) 3963–3969; (h) C. Rocaboy, J.A. Gladysz, Tetrahedron 58 (2002) 4007–4014. [8] (a) L. Gong, A. Streitwieser, J. Org. Chem. 55 (1990) 6235–6236; (b) P. Bernardelli, O.M. Moradei, D. Friedrich, J. Yang, F. Gallou, B.P. Dyck, R.W. Doskotch, T. Lange, L.A. Paquette, J. Am. Chem. Soc. 123 (2001) 9021–9032; (c) S. Kobayashi, I. Hachiya, Tetrahedron Lett. 33 (1992) 1625–1627; (d) S. Kobayashi, I. Hachiya, J. Org. Chem. 59 (1994) 3590–3596. [9] J.A. Dean, Lange’s Handbook of Chemistry, 13th ed., McGraw-Hill, New York, 1985, pp. 5–14.
Aldol condensations of aldehydes and ketones catalyzed by rare earth(III) perfluorooctane sulfonates in fluorous solvents Wen-Bin Yi, Chun Cai * Chemical Engineering College, Nanjing University of Science and Technology, Nanjing 210094, China Received 8 September 2005; accepted 8 September 2005 Available online 20 October 2005
Abstract Rare earth(III) perfluorooctane sulfonates (RE(OPf)3) catalyze the efficient aldol condensation of different ketones with various aromatic aldehydes in fluorous solvents without the occurrence of any self-condensations. By simple separation of the fluorous phase containing only catalyst, reaction can be repeated several times. # 2005 Elsevier B.V. All rights reserved. Keywords: Aldol condensations; Fluorous biphasic catalysis; Rare earth(III) perfluorooctanesulfonates; Perfluorocarbon
1. Introduction Aldol condensation reactions are important synthetic reactions and in classical methods, they were performed in the presence of strong acids or bases [1]. In order to do these reactions under neutral conditions, some metal ions are used as catalyst or reagent [2]. For example, the use of different complexes of metal(II) ions, such as Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) with different ligands have been used for aldol-condensations [2a]. Recently, a new kind of Lewis acids of rare earth(III) perfluorooctane sulfonates (RE(OSO2C8F17)3, RE(OPf)3, RE = Sc, Y, La–Lu) was of special interest [3–5]. The characteristic features of the catalyst include low hygroscopicity, ease of handling, robustness for the recycling using and high solubility in fluorous solvent [4]. On the other hand, perfluorocarbon solvents, especially perfluoroalkanes have some unique properties which make them attractive alternatives for conventional organic solvents [6]. The compounds functionalized with perfluorinated groups often dissolve preferentially in fluorous solvents and this property can be used to extract fluorous components from reaction mixtures [7]. Aldol condensations of aldehydes and ketones catalyzed by rare earth(III) trifluoromethanesulfonates (RE(OSO2CF3)3, RE(OTf)3) were reported [8]. However,
* Corresponding author. Fax: +86 25 84315030. E-mail address: [email protected] (C. Cai). 0022-1139/$ – see front matter # 2005 Elsevier B.V. All rights reserved. doi:10.1016/j.jfluchem.2005.09.004
reusing of these catalysts required tedious work up procedures such as filtration, purification and drying. Therefore, we believe that the application of fluorous phase separation techniques in catalysis can be used to the aldol condensation catalyzed by RE(OPf)3 which has stronger Lewis acidity than RE(OTf)3. In this paper, a green process of aldol condensations of aldehydes and ketones catalyzed by rare earth(III) perfluorooctane sulfonates in fluorous solvents was studied. 2. Results and discussion Due to the importance of methylene structural unit which are found in many naturally occurring compounds and antibiotics and the use of a,a0 -bis(substituted) benzylidene cycloalkanones as precursors for synthesis of bioactive pyrimidine derivatives, condensation of cyclopentanone and cyclohexanone with aldehydes and ketones were of special interest [2f]. Thus, we studied the cross-condensations of cyclopentanone and cyclohexanone with different aromatic aldehydes such as, benzaldehyde, p-chlorobenzaldehyde, p-nitrobenzaldehyde, pmethylbenzaldehyde, p-methoxybenz-aldehyde and cinnamaldehyde. Firstly, The reaction of cyclohexanone with benzaldehyde was adopted for the evaluation of catalysts (Scheme 1). The results are summarized in Table 1. Among these catalysts, Sc(OPf)3 and Yb(OPf)3 are the most efficient catalysts for the condensation. This would be ascribed to the higher Lewis acidity of Sc(OPf)3 and Yb(OPf)3 than those of other RE(OPf)3 [9]. The control experiment elucidates that no product of cross-
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Scheme 1. Scheme 2.
condensations could be obtained in the absence of catalyst and fluorous solvent. In addition, we found that a catalyst loading of only 0.4 mol% was required when using fluorous phase technology. Next, the effect of fluorous solvents such as, perfluorohexane (C6F14), perfluoromethylcyclohexane (C7F14), perfluorotoluene (C7F8), perfluorooctane (C8F18), perfluorooctyl bromide (C8F17Br) and perfluorodecalin (C10F18, cis and trans-mixture) was examined for the condensations (Table 1, entries 16–21). The results showed that yields of the desired products in perfluorooctane (C8F18) and perfluorooctyl bromide (C8F17Br) were lower than other solvents. The fluorous solvents perfluorohexane (C6F14) and perfluorotoluene (C7F8) are in fact miscible with reaction substrates such as cyclohexanone at room temperature. Thus, it is impossible to recover fluorous phase by phase-separation. At the same time, we found that during repeated condensation reactions the loss of fluorous solvent is very serious when using perfluoromethylcyclohexane (C7F14) as a fluorous solvent because it is very volatile (bp 76 8C). Therefore, perfluorodecalin (C10F18, cis and transmixture) is the best fluorous solvent for the condensation. Heptadecafluorooctane-sulfonic acid (C8F17SO3H, PfOH) itself can promote the reaction, but it was found to be less effective than RE(OPf)3.
Table 1 Condensation of cyclohexanone with benzaldehydea Entry
Catalyst
Fluorous solvent
Yield (%)b
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22
Sc(OPf)3 Y(OPf)3 La(OPf)3 Ce(OPf)3 Pr(OPf)3 Nd(OPf)3 Sm(OPf)3 Eu(OPf)3 Gd(OPf)3 Tb(OPf)3 Dy(OPf)3 Ho(OPf)3 Er(OPf)3 Tm(OPf)3 Lu(OPf)3 Yb(OPf)3 Yb(OPf)3 Yb(OPf)3 Yb(OPf)3 Yb(OPf)3 Yb(OPf)3 PfOH
C10F18 c C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 C10F18 CF3(CF2)4CF3 C6F5CF3 C6F13CF3 CF3(CF2)6CF3 CF3(CF2)6CF2Br C10F18
96 78 69 80 60 88 73 66 77 72 84 86 90 79 78 95 89 97 96 82 81 53
a b c
The mole ratio of cyclohexane to benzaldehyde in all cases is 5:3. Isolated yields based on the benzaldehyde. .
Table 2 Condensation of cyclopentanone and cyclohexanone with various aromatic aldehydesa Entry
N
Ar
Temperature (8C)
Time (h)
Yield (%) b
1 2 3 4 5 6 7 8 9 10 11
1 1 1 1 1 1 0 0 0 0 0
4-ClPh 4-CH3Ph 4-CH3OPh 4-NO2Ph Cinnamyl Furfuryl Ph 4-CH3OPh 4-NO2Ph Cinnamyl Furfuryl
120 120 120 120 120 120 120 120 120 120 120
12 4 18 24 16 24 8 18 24 8 24
95 92 94 97 96 89 92 91 95 93 86
a b
The mole ratio of ketone to aromatic aldehyde in all cases is 5:3. Isolated yields based on the benzaldehyde.
In order to seek out a practical, useful aldol condensation process, we decided to use the relatively cheap and similarly active catalyst Yb(OPf)3 and perfluorodecalin (C10F18, cis and trans-mixture) as a fluorous solvent for condensations of cyclopentanone and cyclohexanone with various aromatic aldehydes (Scheme 2). The results are shown in Table 2. The reactions were finished within 4–24 h and excellent yields (86– 97%) of a,a0 -bis(substituted) benzylidene cyclopentanones and cyclohexanones were obtained, regardless of the kind of substituent group on benzaldehyde. Under the conditions described in Table 2, Yb(OPf)3 catalyzed the efficient cross aldol condensations without the occurrence of any selfcondensations. In order to ascertain the scope and limitation of this catalyzed condensation, the use of the catalytic systems was extend to condensation of aliphatic and aromatic ketones with various aldehydes (Scheme 3, Table 3). The reaction products were isolated and identified as a,b-unsaturated ketones, and no side reactions were observed. Based on 1H NMR and GC–MS data, the reaction was found to give E-stereoisomer as sole product. The purity of the products thus obtained was consistently high, probably because the perflates-catalyzed reactions took place under neutral conditions. In general, reactions between aromatic aldehydes and ketones gave good results, but not those of aliphatic compounds. The condensations of p-substituted benzaldehyde with p-substituted acetophenones yielded the corresponding chalcones and the
Scheme 3.
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Table 3 Condensation of acyclic ketones with various aromatic aldehydesa Entry
R1
R2
R3
Temperature (8C)
Time (h)
Yield (%) b
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19
Ph 4-CH3OPh 4-NO2Ph Ph Ph Ph Ph Ph Ph CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3 CH3
H H H H H H H H H H H CH3 CH3 C2H5 C2H5 H H CH3 CH3
Ph Ph Ph 4-ClPh 4-CH3Ph 4-CH3OPh 4-NO2Ph Cinnamyl (CH3)2CH Ph 4-CH3OPh Ph 4-CH3OPh Ph 4-CH3OPh C2H5 C3H7 C2H5 C3H7
120 120 120 120 120 120 120 120 80 80 80 80 80 80 80 60 80 60 80
24 24 24 24 24 24 24 32 72 48 48 48 48 48 48 72 72 72 72
85 69 95 89 76 65 96 41 32 77 75 58 51 46 37 7 4 6 3
a b
The mole ratio of ketone to aromatic aldehyde in all cases is 5:3. Isolated yields based on the benzaldehyde.
product yields were remarkably affected by the subsitituent groups of either aldehydes of ketones: reactants having electron-withdrawing substituents gave high yields and those having electron-donating ones gave low yields. The reactions of various aromatic aldehydes with acetone gave corresponding a,b-unsaturated ketones in good yields. It was known that the base-catalyzed reactions of 2-butanone with benzaldehyde gave preferentially the condensation product at C1 of ketone, while the acid catalyzed reaction occurred preferentially at C3. The obtained results from condensation of 2-butanone and 2pentanone with different aromatic aldehydes showed excellent regioselectivity with the occurrence of condensation from C3. The catalyst Yb(OPf)3 system appeared to show no catalytic activity for the condensation of the aliphatic ketones such as acetone and 2-butanone with the aliphatic aldehydes, propanal and pentanal. Attempts were made to recycle the catalytic system. The condensations of cyclohexanone and acetophenone with benzaldehyde under the conditions as mentioned above were run for five consecutive cycles, respectively, furnishing the corresponding a,a0 -bis(substituted) benzylidene cyclopentanones with 95, 95, 93, 92, 92% isolated yields and chalcone with 85, 84, 85, 84, 83% isolated yields. The robustness of the catalyst for recycling using may partly be attributed to the water-repellent nature of the perfluoroalkane chain ‘‘(–CF2– CF2–)n’’ of RE(OPf)3 which refuses the approach of water or acid molecules to the central metal cation, thus maintaining its high Lewis acidity [9]. When the reaction was finished, the reaction mixture was cooled to room temperature. The fluorous phase with RE(OPf)3 catalysts can separate from the organic layer return to the bottom layer. Based on GC– MS data, no loss of fluorous solvent to the organic phase can be detected. The separated fluorous phase containing only catalyst
could be reused for the next reaction without any treatment, and this workup procedure of recycling was accomplished by simple phase-separation. In conclusion, RE(OPf)3 are demonstrated to be new and highly effective catalysts for condensations of aromatic aldehyhes and ketones in fluorous solvents. By simple separation of the fluorous phase containing only catalyst, reaction can be repeated several times. The simple procedures as well as easy recovery and reuse of this novel catalytic system are expected to contribute to the development of more benign aldol condensation. 3. Experimental 3.1. General MPs were obtained with Shimadzu DSC-50 thermal analyzer. IR spectra were recorded on a Bumem MB154S infrared analyzer. 1H NMR spectra were measured on Bruke Advance RX300. Mass spectra were recorded with a Saturn 2000GC/MS instrument. Inductively coupled plasma (ICP) spectra were measured on Ultima2C apparatus. Elemental analyses were performed on a Yanagimoto MT3CHN corder. Commercially available reagents were used without further purification. 3.2. Typical procedure for preparation of RE(OPf)3 RE(OPf)3 was prepared according to the literatures [4] (Method A). The mixture of PfOH solution (aq) and YbCl36H2O solution (aq) was stirred at room temperature (Method B). The mixture of PfOH solution (aq) and Yb2O3 powder was stirred at boiling. In both methods, the resulting gelatin-like solid was collected, washed and dried at 150 8C in vacuo to give a white
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solid, which does not have a clear melting point up to 500 8C, but shrinks around 380 8C and 450 8C. IR (KBr) n (cm1) 1237 (CF3), 1152 (CF2), 1081 (SO2), 1059 (SO2), 747 (S–O) and 652 (C–S). ICP: Calcd. for C24O9F51S3Yb: Yb, 10.30%. Found: Yb, 9.88%. Anal. Calcd. for C24O9F51S3YbH2O: C, 17.21%; H, 0.10%. Found: C, 17.03%; H, 0.18%. 3.3. Typical procedure for condensation of aldehydes with ketones Benzaldehyde (1.2 ml, 12 mmol) was slowly added into a mixture of Yb(OPf)3 (80 mg, 0.048 mmol), cyclohexone (2.1 ml, 20 mmol) and perfluorodecalin (C10F18, cis and trans-mixture, 1.5 ml). The mixture was stirred at 120 8C for 12 h. Then, the fluorous layer on the bottom was separated for the next condensation. The reaction mixture (organic phase) was poured into cold ethanol (20 ml) and stirred for 5 min and filtered. The crystalline product was further washed subsequently with water (10 ml), 10% NaHCO3 solution (10 ml) and water (10 ml 2), cold ethanol (10 ml) and dried to give the product 2,6-dibenzylidenecyclohexanone (1.56 g, 95%). 2,6-Dibenzylidenecyclohexanone. A yellow solid; mp 116– 118 8C (lit2e 116–117 8C). IR (KBr) n 3020, 2924, 1657, 1604, 1570, 1271, 1142, 770, 692 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.76–1.87 (m, 2H), 2.95 (t, J = 6.4 Hz, 4H), 7.30–7.48 (m, 10H), 7.80 (s, 2H). MS (EI) m/z 273 (M+). 2,6-Di(p-chlorobenzylidene)cyclohexanone. A brown solid; mp 149–151 8C (lit2f 147–148 8C). IR (KBr) n 2930, 1660, 1606, 1576, 1262, 828 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.76–1.84 (m, 2H), 2.90 (t, J = 6.0 Hz, 4H), 7.36–7.43 (m, 8H), 7.73 (s, 2H). MS (EI) m/z 346 (M+ + 4), 344 (M+ + 2), 342 (M+). 2,6-Di(p-methylbenzylidene)cyclohexanone. A yellowish solid; mp 170–171 8C (lit2f 170 8C). IR (KBr) n 2980, 2944, 1666, 1600, 1560, 1268, 1140, 760, 698 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.78–1.86 (m, 2H), 2.30 (s, 6H), 2.92 (t, J = 6.2 Hz, 4H), 7.22–7.38 (m, 8H), 7.76 (s, 2H). MS (EI) m/z 301 (M+). 2,6-Di(p-methoxybenzylidene)cyclohexanone. A yellow solid; mp 203–204 8C (lit2e 203–204 8C). IR (KBr) n 3020, 2924, 1657, 1604, 1570, 1271, 1142, 770, 692 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.80–1.83 (m, 2H), 2.94 (t, J = 6.0 Hz, 4H), 3.86 (s, 6H), 6.94–7.40 (m, 8H), 7.77 (s, 2H). MS (EI) m/z 333 (M+). 2,6-Di(p-nitrobenzylidene)cyclohexanone. A russety solid; mp 158–160 8C (lit2e 159 8C). IR (KBr) n 3082, 2925, 1663, 1606, 1576, 1525, 1346, 807 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.84–1.90 (m, 2H), 2.97 (t, J = 5.6 Hz, 4H), 7.60–8.22 (m, 8H), 8.32 (s, 2H). MS (EI) m/z 363 (M+). 2,6-Dicinnamylidenecyclohexanone. A yellowish solid; mp 179 8C (lit2e 180 8C). IR (KBr) n 3028, 2920, 1653, 1610, 1540, 1180,737, 690 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.96–2.16 (m, 2H), 2.86 (t, J = 6.4 Hz, 4H), 6.60 (d, J = 16.2 Hz, 2H), 6.83 (d, J = 16.2 Hz, 2H), 6.86–7.42 (m, 10H), 7.72 (s, 2H). MS (EI) m/z 325 (M+). 2,6-Difurfurylidenecyclohexanone. A purple solid; mp 140– 142 8C (lit2e 140–141 8C). IR (KBr) n 3149, 2940, 1643, 1590,
1546, 1278, 1147, 1010, 764 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.16–2.54 (m, 2H), 2.95 (d, 4H), 6.20–7.72 (m, 8H). MS (EI) m/z 253 (M+). 2,6-Dibenzylidenecyclopentanone. A brown solid; mp 188 8C (lit2e 188–189 8C). IR (KBr) n 3100, 2926, 1654, 1598, 1460,1260, 760, 674 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.76 (t, 4H), 7.26–7.38 (m, 10H), 7.68 (s, 2H). MS (EI) m/z 259 (M+). 2,6-Di(p-methoxybenzylidene)cyclopentanone. A green solid; mp 211–212 8C (lit2e 210–211 8C). IR (KBr) n 2962, 2841, 1649, 1595, 1506, 1253, 1020, 834 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 3.09 (t, 4H), 3.86 (s, 6H), 6.96–7.56 (m, 8H), 7.58 (s, 2H). MS (EI) m/z 319 (M+) 2,6-Di(p-nitrobenzylidene)cyclopentanone. A russety solid; mp 230–231 8C (lit2e 230–231 8C). IR (KBr) n 3105, 2847, 1706, 1605, 1521, 1344, 816 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 3.07 (t, 4H), 7.62–8.12 (m, 8H), 8.27 (s, 2H). MS (EI) m/z 349 (M+). 2,6-Dicinnamylidenecyclopentanone. A purple solid; mp 223–224 8C (lit2e 222–224 8C). IR (KBr) n 3024, 2925, 1698, 1625, 1598, 1447, 690 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.86 (m, 4H), 6.70 (d, J = 16.2 Hz, 2H), 6.76 (d, J = 16.2 Hz, 2H), 6.81–7.70 (m, 10H), 7.72 (s, 2H). MS (EI) m/ z 311 (M+). 2,6-Difurfurylidenecyclopentanone. A russety solid; mp 161 8C (lit2e 160–162 8C). IR (KBr) n 3130, 2931, 1683, 1625, 1600, 1287, 1240, 754 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.98 (m, 4H), 2.95 (d, 4H), 6.30–7.62 (m, 8H). MS (EI) m/z 239 (M+). Chalcone. A yellowish solid; mp 55–57 8C (lit2b 57–58 8C). IR (KBr) n 3230, 2934, 1830, 1725, 1650, 1287, 754, 685 cm1. 1 H NMR (300 MHz, TMS, CDCl3) d 6.12 (d, J = 16.0 Hz, 1H), 7.26 (d, J = 16.0 Hz, 1H), 7.10–7.32 (m, 5H), 7.42–7.92 (m, 5H). MS (EI) m/z 207 (M+). 40 -Methoxychalcone. A russety solid; mp 109–110 8C (lit2b 109–110 8C). IR (KBr) n 3200, 2886, 1830, 1725, 1660, 1212, 854, 734 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 3.78 (s, 3H), 6.10 (d, J = 16.0 Hz, 1H), 7.22 (d, J = 16.0 Hz, 1H), 7.12– 7.62 (m, 9H). MS (EI) m/z 238 (M+). 40 -Nitrochalcone. A yellow solid; mp 151–153 8C (lit2b 151– 152 8C). IR (KBr) n 3010, 2896, 1705, 1680, 1643, 1470, 921, 845 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 6.32 (d, J = 16.1 Hz, 1H), 7.36 (d, J = 16.1 Hz, 1H), 7.15–7.36 (m, 5H), 7.52–8.26 (m, 4H). MS (EI) m/z 253 (M+). 4-Chlorochalcone. A yellow solid; mp 114–115 8C (lit2b 114–117 8C). IR (KBr) n 3086, 2910, 1780, 1712, 1650, 1207, 914, 746 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 6.20 (d, J = 16.0 Hz, 1H), 7.12 (d, J = 16.0 Hz, 1H), 6.22 (d, 2H), 7.10– 7.32 (m, 4H), 7.38–8.01 (m, 5H). MS (EI) m/z 244 (M+ + 2), 242 (M+). 4-Methylchalcone. A yellowish solid; mp 98–99 8C (lit2b 97– 98 8C). IR (KBr) n 3213, 2914, 1760, 1698, 1650, 1090, 942, 850, 718 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.33 (s, 3H), 6.01 (d, J = 16.4 Hz, 1H), 7.02 (d, J = 16.4 Hz, 1H), 7.01–7.32 (m, 4H), 7.36–7.82 (m, 5H). MS (EI) m/z 221 (M+). 4-Methoxychalcone. A russety solid; mp 75–76 8C (lit2b 75– 77 8C). IR (KBr) n 3302, 2986, 1830, 1725, 1660, 1187, 934,
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820 cm1. 1H NMR (300 MHz, TMS, CDCl3) n 3.73 (s, 3H), 5.93 (d, J = 16.0 Hz, 1H), 6.88 (d, J = 16.0 Hz, 1H), 6.92–7.19 (m, 4H), 7.32–7.99 (m, 5H). MS (EI) m/z 238 (M+). 4-Nitrochalcone. A brown solid; mp 158–160 8C (lit2b 158– 160 8C). IR (KBr) n 3236, 2910, 1870, 1675, 1660, 1470, 918, 840 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 6.34 (d, J = 16.1 Hz, 1H), 7.39 (d, J = 16.1 Hz, 1H), 7.35–7.66 (m, 3H), 7.72–8.34 (m, 4H). MS (EI) m/z 252 (M+). Cinnamylideneacetophenone. A yellow solid; mp 103– 104 8C (lit2a 104–105 8C). IR (KBr) n 3112, 3001, 2950, 1875, 1746, 1634, 1180, 940, 829 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 6.28 (d, J = 15.9 Hz, 1H), 7.12 (d, J = 15.9 Hz, 1H), 7.05–7.24 (m, 5H), 6.84 (d, J = 15.4 Hz, 1H), 7.76 (d, J = 15.4 Hz, 1H), 7.45–7.83 (m, 5H). MS (EI) m/z 233 (M+). 1-Phenyl-4-methyl-2-penten-1-one. A yellowish liquid (lit2b); IR (CHCl3) n 1780, 1674, 1652, 1480, 927, 840, 762 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.15 (d, 6H), 1.70 (m, 1H), 6.08 (t, J = 15.5 Hz, 1H), 6.76 (d, J = 15.5 Hz, 1H), 7.32–7.86 (m, 5H). MS (EI) m/z 173 (M+). Benzylideneacetone. A yellowish solid; mp 40–41 8C (lit2b 41–42 8C). IR (KBr) n 3108, 2960, 1835, 1720, 1664, 1180, 943, 817 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.39 (s, 3H), 6.65 (d, J = 16.5 Hz, 1H), 7.45 (d, J = 16.5 Hz, 1H), 7.35– 7.72 (m, 5H). MS (EI) m/z 147 (M+). 4-Methoxybenzylideneacetone. A yellowish solid; mp 44– 45 8C (lit2b 44–46 8C). IR (KBr) n 3202, 2946, 1780, 1724, 1589, 1182, 920, 826, 764 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.26 (s, 3H), 3.82 (s, 3H), 6.50 (d, J = 16.0 Hz, 1H), 7.45 (d, J = 16.0 Hz, 1H), 7.10–7.32 (m, 4H). MS (EI) m/z 178 (M+). 3-Benzylidene-2-butanone. A yellowish liquid (lit2f); IR (CHCl3) n 3026, 2870, 1765, 1674, 1652, 1487, 927, 834 cm1. 1 H NMR (300 MHz, TMS, CDCl3) d 2.01 (d, 3H), 2.40 (s, 3H), 7.18–7.26 (m, 5H), 7.35 (s, 1H). MS (EI) m/z 159 (M+). 3-(2-Methoxybenzylidene)-2-butanone. A yellowish liquid (lit2f); IR (CHCl3) n 3129, 2976, 1763, 1660, 1486, 937, 835, 762 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 2.02 (d, 3H), 2.37 (s, 3H), 3.82 (s, 3H), 6.83–7.02 (m, 4H), 7.36 (s, 1H). MS (EI) m/z 190 (M+). 3-Benzylidene-2-pentanone. A yellowish liquid (lit2f); IR (CHCl3) n 3039, 2862, 1760, 1656, 1482, 923, 846, 757 cm1. 1 H NMR (300 MHz, TMS, CDCl3) d 1.86–2.46 (m, 5H), 2.40 (s, 3H), 7.12–7.22 (m, 5H), 7.40 (s, 1H). MS (EI) m/z 173(M+). 3-(4-Methoxybenzylidene)-2-pentanone. A yellowish liquid (lit2f); IR (CHCl3) n 3124, 2975, 1756, 1650, 1475, 903, 842, 748 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.84–2.44 (m, 5H), 2.38 (s, 3H), 3.79 (s, 3H), 6.86–7.13 (m, 4H), 7.40 (s, 1H). MS (EI) m/z 204 (M+). 3-Hexen-2-one. A colorless liquid (lit2b); IR (CHCl3) n 1770, 1653, 1472, 1312, 920, 832, 756 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.12 (t, 3H), 1.96 (m, 2H), 2.36 (s, 3H), 6.27 (m, J = 15.9 Hz, 1H), 7.12 (d, J = 15.9 Hz, 1H). MS (EI) m/z 97 (M+). 3-Hepten-2-one. A colorless liquid (lit2b); IR (CHCl3) n 1782, 1624, 1489, 1310, 912, 796, 724 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 0.96–1.37 (m, 5H), 1.92 (m, 2H),
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2.30 (s, 3H), 6.18 (m, J = 15.9 Hz, 1H), 7.16 (d, J = 15.9 Hz, 1H). MS (EI) m/z 111 (M+). 3-Methyl-3-hexen-2-one. A colorless liquid (lit2b); IR (CHCl3) n 1789, 1641, 1601, 1472, 1319, 1178, 920, 820, 783 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 1.04 (t, 3H), 1.93 (s, 3H), 2.04 (m, 2H), 2.35 (s, 3H), 6.5 (m, 2H). MS (EI) m/ z 111 (M+). 3-Methyl-3-hepten-2-one. A colorless liquid (lit2b); IR (CHCl3) n 1802, 1765, 1641, 1439, 1310, 1238, 918, 823, 763 cm1. 1H NMR (300 MHz, TMS, CDCl3) d 0.92–1.41 (m, 5H), 1.87 (s, 3H), 1.96 (m, 2H), 2.28 (s, 3H), 6.52 (m, H). MS (EI) m/z 125 (M+). Acknowledgements We thank the National Defence Committee of Science and Technology (40406020103) for financial support. We also thank the Zhen-Ya Rare Earth Co. Ltd. for providing several kinds of rare earth oxides. References [1] (a) A.T. Nielsen, W.J. Houlihan, Org. React. 16 (1968) 1; (b) R.L. Reeves, in: S. Patai (Ed.), Chemistry of Carbonyl Group, Wiley/ Interscience, New York, 1966, pp. 580–593. [2] (a) K. Irie, K. Watanabe, Bull. Chem. Soc. Jpn. 53 (1980) 1366–1371; (b) K. Watanabe, A. Imazawa, Bull. Chem. Soc. Jpn. 55 (1982) 3208– 3211; (c) T. Nakamo, S. Irifune, S. Umano, A. Inada, Y. Ishii, M. Ogawa, J. Org. Chem. 52 (1987) 2239–2244; (d) Y. Yoshida, R. Hayashi, H. Sumihara, Y. Tanabe, Tetrahedron Lett. 38 (1997) 8727–8730; (e) M. Zheng, L. Wang, J. Shao, Q. Zhong, Synth. Commun. 27 (1997) 351–354; (f) N. Iranpoor, F. Kazemi, Tetrahedron 54 (1998) 9475–9480; (g) Y. Zheng, F.T.T. Ng, G.L. Rempel, Ind. Eng. Chem. Res. 40 (2001) 5342–5349; (h) R. Uma, M. Davies, C. Crevisy, R. Gree, Tetrahedron Lett. 42 (2001) 3069–3072; (i) D. Reardon, J. Guan, S. Gambarotta, G.P.A. Yap, D.R. Wilson, Organometallics 21 (2002) 4390–4397; (j) M. Sasidharan, R. Kumar, J. Catal. 220 (2003) 326–332; (k) A. Yanagisawa, T. Sekiguchi, Tetrahedron Lett. 44 (2003) 7163– 7166; (l) D. Mendez, E. Klimova, T. Klimova, L. Fernando, S. Hernondez, J. Organometall. Chem. 679 (2003) 10–13; (m) J. Mlynarski, M. Mitura, Tetrahedron Lett. 45 (2004) 7549–7552; (n) A. Clerici, N. Pastori, O. Porta, J. Org. Chem. 70 (2005) 4174– 4176. [3] (a) S. Kobayashi, I. Hachiya, T. Takahori, M. Araki, M. Ishitani, Tetrahedron Lett. 33 (1992) 6815–6818; (b) S. Kobayashi, H. Ishitani, I. Hachiya, M. Araki, Tetrahedron 50 (1994) 11623–11636; (c) K. Manabe, H. Oyamada, K. Sugita, S. Kobayashi, J. Org. Chem. 64 (1999) 8054–8057; (d) T. Kitazume, H. Nakano, Green Chem. 3 (1999) 179–181; (e) S. Kobayashi, A. Kawada, S. Mitamura, J. Matsuo, T. Suchiya, Bull. Chem. Soc. Jpn. 73 (2000) 2325–2333; (f) S. Kobayashi, I. Komoto, J. Matsuo, Adv. Synth. Catal. 343 (2001) 71– 74; (g) M. Shi, S.-C. Cui, Chem. Commun. 9 (2002) 994–995. [4] T. Hanamoto, Y. Sugimoto, Y.Z. Jin, J. Inanaga, Bull. Chem. Soc. Jpn. 70 (1997) 1421–1426. [5] M. Shi, S.-C. Cui, J. Fluorine Chem. 116 (2002) 143–147.
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