Abstract
Cheap, abundant but seldom-employed Ca(OH)2 was found to be an excellent low-loading (5–10 mol%) catalyst for Claisen-Schmidt condensation of aldehydes with methyl ketones under mild conditions. It was interesting that dilute aqueous ethanol (20 v/v%) was unexpectedly discovered to be the optimal solvent. The reaction was scalable at least to 100 mmol and calcium could be precipitated by CO2 and removed by filtration. Evaporation of solvent directly afforded the product in the excellent 96% yield with high purity, as confirmed by its 1H NMR spectrum.
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Introduction
α,β-Unsaturated ketones, including dimethylidene acetone derivatives, are not only important building blocks in organic synthesis, but also key chemicals in many fields including perfumery, biochemistry, agriculture, food chemistry, polymer and material science and others1,2,3,4. Therefore, the synthesis of these compounds is of great importance in both academic and industrial circles. Among reported works, Claisen-Schmidt condensation appears to be the most practical method to prepare α,β-unsaturated ketones owing to its directness, clean procedures and accessible starting materials. Despite being discovered over 100 years ago, the enthusiasm for Claisen-Schmidt condensations never reduces and in recent years, a series of novel catalysts have been developed for this reaction, such as solid bases5,6, nano catalysts7,8, ionic liquid catalysts9, fluorous based catalysts10,11, metal-organic frame works (MOFs)12 and organocatalysts13,14. Nevertheless, cheap and abundant NaOH would be expected to be the most common catalyst for the reaction due to its availability in laboratory and indeed this method is still widely employed up to the present15,16,17. But reactions performed in strong alkaline conditions are corrosive to equipment and generate unmanageable and corrosive solid waste. These drawbacks have limited the large-scale application of NaOH. Moreover, methods for the synthesis of dimethylidene acetone derivatives, especially for those dissymmetrically substituted compounds, have not been well documented yet. Thus, developing novel alternative synthetic methodologies with broad scope using mild and common base catalysts is not only desirable but timely for the field.
Calcium hydroxide is also a readily accessible base and compared with NaOH, it is much cheaper and less alkaline. Moreover, Ca(OH)2 is easily neutralized and precipitated by CO2, which is beneficial from the point of industrial use. However, despite several well-known applications in industrial production, examples of the employment of Ca(OH)2 as a base catalyst in organic synthesis are rare18. As part of our continuing cooperative research projects with industrial partners to develop green synthetic methodologies19,20,21,22,23,24,25,26,27,28, we reported an organoselenium-catalyzed green oxidation of α,β-unsaturated ketones to prepare vinyl esters, which serve as versatile copolymers in material science24. To facilitate industrial application, a green and practical synthesis of α,β-unsaturated ketones (the starting material for vinyl ester synthesis) was desired. To that end, we investigated the Ca(OH)2-catalyzed Claisen-Schmidt condensations to prepare α,β-unsaturated ketones. During this work, dilute aqueous ethanol was unexpectedly found to be the optimal solvent and calcium could be precipitated by CO2 and removed by filtration to afford high purity products after solvent evaporation. The method allows comprehensive access to versatile α,β-unsaturated ketones, including the challenging dissymmetrically substituted dimethylidene acetone derivatives. Herein, we wish to report our findings.
Results
We initially chose the Ca(OH)2-catalyzed Claisen-Schmidt condensation of benzaldehyde 1a with acetone 2a as the model reaction to find optimal conditions (Fig. 1). After heating 1a, 2a and 10 mol% of Ca(OH)2 in EtOH at 50 °C for 20 h, the product benzylideneacetone 3a could be isolated in 68% yield (Table 1, entry 1). During the reaction process, we observed Ca(OH)2 precipitation at the bottom of the tube, which implied the low efficiency of alkali utilization. Therefore, water was then added to increase the Ca(OH)2 solubility. When the reaction was performed in EtOH/H2O (80:20), it was significantly accelerated and finished in 16 h, giving 3a in 69% yield (entry 2). The reaction was further accelerated and the product yields were enhanced greatly by increasing the proportional of water in the solvent (entries 3–4). Surprisingly, EtOH/H2O (20:80) as solvent gave the highest product yield in 85% (entry 4). Increased ratios of water in the solvent only resulted in reduced product yield and extended reaction times (entry 5), possibly due to the reduced substrate dissolution that inhibited the reaction. When the reactions were taken in highly diluted aqueous EtOH (entry 6) or pure water (entry 7), no product 3a was observed. It is notable that the combination of EtOH with water played a key role in this reaction. A series of parallel reactions showed that the effect of EtOH/H2O was not only solvent for both organic substrates and inorganic base, but it also activated the Ca(OH)2. Experiments performed in acetone or acetone/EtOH resulted in very low product yields despite the reaction temperature. For details, please see the Supplementary Information.
Condensation of 1a with 2a.
With the optimized conditions in hand, a series of aldehydes 1 and ketones 2 were then employed to examine the scope of the reaction (Fig. 2). Results in Table 2 clearly show that the electron-enriched aldehydes had reduced reactivities for this reaction, which resulted in both extended reaction times and decreased product yields (Table 2, entries 2–5 vs. 1). For 4-methoxybenzaldehyde 1e, the reaction should be carried out at room temperature with excess acetone, otherwise the dialkylated product (1E,4E)-1,5-bis(4-methoxyphenyl)penta-1,4-dien-3-one 4c was obtained instead of the desired (E)-4-(4-methoxyphenyl)but-3-en-2-one 3e (Table 2, entry 5). The electron-deficient aldehydes obviously had higher reactivities and their reactions were accelerated, but resulted in reduced product yields due to the generation of a series of unidentified byproducts (Table 2, entries 6–11). The reactions of electron-deficient aldehydes could be improved using milder conditions. For example, treating 2-chlorobenzaldehyde 1h with acetone under the standard reaction conditions (50 °C) afforded the product 3h in only 40% yield, but the yield could be improved of room temperature (ca. 25 °C), affording 3h in 52% yield (Table 2, entry 8). Similarly, for 4-(trifluoromethyl)benzaldehyde 1j, reaction with acetone under standard conditions gave 3j in very low yield, but was also improved to 72% at room temperature (Table 2, entry 10). The reaction of 4-nitrobenzaldehyde 1k with acetone led to poor product yield, but this was improved at room temperature (Table 2, entry 11). Bulky aldehyde 1l was also tested, giving the desired product 3l in moderate yields (Table 2, entry 12). We were also interested in the synthesis of heterocycle containing α,β-unsaturated ketones because of their bioactivities and potential applications in medicinal chemistry. The reaction of picolinaldehyde 1m with acetone was tested, but gave 3m in very low yield. Fortunately, the reaction could be improved to give 3m in moderate yield under milder conditions using excess acetone (Table 2, entries 13). Interestingly, the reaction of thiophene-2-carbaldehyde 1n with acetone afforded 3n quickly in the excellent 90% yield under the standard conditions (Table 2, entry 14). The α,β-unsaturated aldehyde 1o was also good substrate for the reaction, giving 3o in 91% yield (Table 2, entry 15). The reaction of aliphatic aldehyde gave the product in low yield (Table 2, entry 16).
Substrate extension of the Ca(OH)2-catalyzed Claisen-Schmidt condensation.
Besides acetone, other methyl ketones could also be employed. The reaction of acetophenone 2b with benzaldehyde 1a led to 3p in 71% in 18 h (Table 2, entry 17). But the electron-riched substrate 2c obviously had lower reactivity and the reaction did not complete even after 48 h (Table 2, entry 18). Reaction of the electron-deficient substrate 2d with 1a led to their product 3r in 68% yield in 40 h, with a series of unidentified by-products observed by TLC (Table 2, entry 19). Reactions of the alkyl methyl ketones 2e and 2f with 1a afforded the corresponding products 3s and 3t in moderate yields (Table 2, entries 20–21). A more detailed substrate expansion table was also given in the Supplementary Information.
The synthesis of the dimethylidene acetone derivatives was our next concern because of the great application potential of these bioactive compounds (Fig. 3). Fortunately, during the previous optimization study, we serendipitously found that the symmetrically substituted dibenzylidene acetone 4a could be easily synthesized in good yield from 1a and 2a at 80 °C (Table 3, entry 1). As shown in Table 3, other symmetrically substituted dimethylidene acetone derivatives could be smoothly synthesized in this way. Obviously, the electron-enriched aldehydes 1b and 1e had poor reactivity for the reaction, giving 4b and 4c in only 31–39% yields (Table 3, entries 2–3). The electron-deficient aldehydes 1f and 1j were much more activated (Table 3, entries 4–5) and the reaction of 1j with acetone even led to 4e in excellent 92% yield (Table 3, entry 5). Heterocycle-substituted aldehydes were also suitable substrates for the reaction, giving corresponding products in moderate to good yields (Table 3, entries 6–7).
Synthesis of symmetrically substituted dimethylidene acetone derivatives.
We also tried to synthesize the dissymmetrically substituted dimethylidene acetone derivatives using this Ca(OH)2-catalyzed methodology (Fig. 4). Initially, the reaction of aldehyde 1a with a stoichiometric amount of 3a led to 4a in 82% yield (Table 4, entry 1). This two-step protocol was then employed to synthesize other dissymmetrically substituted dimethylidene acetone derivatives. Treating aldehydes 1b-q with 3a at 80 °C in the presence of Ca(OH)2 catalyst afforded the corresponding products 4h-4n smoothly (Table 4). The electron-deficient aldehydes led to higher product yield than the electron-riched aldehydes (Table 4, entries 4–5 vs. 2–3). Heterocycle-contained aldehydes 1n and 1p were also fit for the reaction (Table 4, entries 6–7), but the alkyl substrate 1q resulted in poor product yield (Table 4, entry 8).
Synthesis of dissymmetrically substituted dimethylidene acetone derivatives.
The synthetic efficiency could be improved using a one-pot strategy. Although the product yields of the one-pot synthesis were reduced in some cases (Table 4, entries 1,3–4, 6–8), considering of the loss of the starting materials in 3a preparation step (Table 2, entry 1, 85% yield), their total yields were higher than that of the multi-step methods (Table 4, entries 1–8).
The role of Ca(OH)2 in the reaction was investigated through a series of control experiments. Using 20 mol% of NaOH as base afforded 3a in only 47% yield (Table 5, entry 1). But with the addition of 10 mol% of the neutral CaCl2, the yield of 3a could be largely enhanced to 78% (Table 5, entry 5). Similar phenomena were also observed in reactions using organic bases (Table 5, entries 3 vs 4). LiOH, an alkali weaker than NaOH, but with a “hard” alkali metal, led to a significantly elevated 3a yield (Table 5, entries 5 vs 1). These experimental results suggested that the “hard” Ca2+ is the key factor for the excellent catalytic performance.
Finally, to examine the practicability of the method, a 100 mmol scale reaction of 1a with 2a was performed. After the reaction, calcium was precipitated by CO2 and removed through filtration. Evaporation of the solvent directly afforded 3a in 96% yield with high purity (Fig. 5), as confirmed by its 1H NMR spectrum (Fig. 6).
The simple separation procedure for the product.
1H NMR spectrum of the product 3a after the evaporation of solvent.
Conclusion
In conclusion, we have developed a practical synthesis of α,β-unsaturated ketones, including the symmetrically or dissymmetrically substituted dimethylidene acetone derivatives, which are promising compounds for medicinal chemistry. The method employed very low loading (5–10 mol%) Ca(OH)2 catalyst, which could be removed by CO2. The reactions were performed in cheap and benign dilute aqueous ethanol (20 v/v%). This work shows that Ca(OH)2, the abundant but seldom employed base, might find further application in organic synthesis.
Methods
General Considerations
Aldehydes were purchased from the reagent merchant. The liquid aldehydes were distilled under vacuum before use, while the solid aldehydes were recrystallized in EtOH-H2O under N2 before use. Ethanol was analytical pure (AR) and directly used without any special treatment. All reactions were carried out in N2 and monitored by TLC. Melting points were measured by WRS-2A digital instrument. IR spectra were measured on Bruker Tensor 27 Infrared spectrometer. 1H and 13C NMR spectra were recorded on a Bruker Avance 600/400 instrument (600 or 400 MHz for 1H and 150 MHz for 13C NMR spectroscopy) using CDCl3 as the solvent and Me4Si as the internal standard. Chemical shifts for 1H and 13C NMR were referred to internal Me4Si (0 ppm) and J-values were shown in Hz. Mass spectra were measured on a Shimadzu GCMS-QP2010 Ultra spectrometer (EI).
Typical procedure for the synthesis of 3
0.1 mmol of Ca(OH)2 (7.4 mg) was first added into a reaction tube, which was then charged with N2. A solution of 1 mmol of aldehyde 1 and 3 mmol of methyl ketone 2 in EtOH/H2O (1 mL, 20 v/v%) was then injected into the reaction tube. The mixture was heat at 50 °C under N2 protection and the reaction was monitored by TLC. When the reaction terminated, the solvent was evaporated under vacuum and the residue was purified by preparative TLC (eluent: petroleum ether/EtOAc, 2: 1 for 3m, 15: 1 for rest compounds).
Typical procedure for the synthesis of symmetrically substituted dimethylidene acetone derivatives 4
0.1 mmol of Ca(OH)2 (7.4 mg) was first added to a reaction tube, which was then charged with N2. A solution of 2 mmol of aldehyde 1 and 1 mmol of acetone 2a in EtOH/H2O (1 mL, 20 v/v%) was then injected into the reaction tube, which was then sealed under N2 and heat at 80 °C for 48 h. The reaction mixture was isolated by preparative TLC (eluent: petroleum ether/EtOAc, 15: 1).
Typical procedure for the synthesis of dissymmetrically substituted dimethylidene acetone derivatives 4 (multi-step)
0.1 mmol of Ca(OH)2 (7.4 mg) and 1 mmol of 3a were added into a reaction tube, which was then charged with N2. A solution of 1 mmol of aldehyde 1 in EtOH/H2O (1 mL, 20 v/v%) was then injected into the reaction tube. The mixture was heat at 80 °C under N2 for 48 h and then isolated by preparative TLC (eluent: petroleum ether/EtOAc, 15: 1).
Typical procedure for the synthesis of dissymmetrically substituted dimethylidene acetone derivatives 4 (one-pot)
0.1 mmol of Ca(OH)2 (7.4 mg) was first added into a 10 mL round bottom flask, which was then charged with N2. A solution of 1 mmol of aldehyde 1 and 3 mmol of methyl ketone 2 in EtOH/H2O (1 mL, 20 v/v%) was then injected into the reaction tube. The mixture was heat at 50 °C under N2 protection. After 10 h, the solvent was evaporated under vacuum and another solution of 1 mmol of aldehyde 1 in EtOH/H2O (1 mL, 20 v/v%) was then injected. The mixture was heat at 80 °C under N2 for 48 h and isolated by preparative TLC (eluent: petroleum ether/EtOAc, 15:1).
Procedure for the large-scale reaction
To a 250 mL three-neck flask, 10 mmol of Ca(OH)2 (0.74 g) was added. The flask was then charged with N2. A solution of 100 mmol of benzaldehyde 1a and 300 mmol of acetone 2a in 100 mL EtOH/H2O (20 v/v%) was then injected. The mixture was stirred at 50 °C under N2 protection for 10 h and then cooled to room temperature. CO2 was then charged into the liquid and the pH was controlled to 7.0 (monitored by a pH meter). The precipitated CaCO3 was removed by filtration and the filtrate was collected. After the evaporation of the solvent, 14.0 g of the product 3a was obtained in the excellent 96% yield. The product was directly sent to 1H NMR analysis without any further purification and the results in Fig. 2 confirmed its high purity.
Characterization of the products (For spectra of the compounds, please see the Supplementary Information)
(E)-4-Phenylbut-3-en-2-one 3a
124.3 mg, 85%; Solid, m. p. 40.4–40.9 °C (lit. 40–41 °C); IR (KBr): 3027, 2923, 1958, 1668, 1609, 1358, 1256, 975, 749, 690 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.53–7.38 (m, 5H), 7.50 (d, J = 16.2 Hz, 1H), 6.71 (d, J = 16.2 Hz, 1H), 2.37 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 198.4, 143.5, 134.4, 130.6, 129.0, 128.3, 127.1, 27.5; MS (EI, 70 eV): m/z (%) 147 (5) [M+ + 1], 146 (47) [M+], 103 (100), 131 (85), 145 (58); Known compound29.
(E)-4-(p-Tolyl)but-3-en-2-one 3b
133.0 mg, 83%; Oil; IR (film): 3293, 3025, 2920, 1665, 1610, 1512, 1357, 1256, 977, 801, 601 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.46 (d, J = 16.2 Hz, 1H), 7.40 (d, J = 7.8 Hz, 2H), 7.16 (d, J = 7.8 Hz, 2H), 6.65 (d, J = 16.2 Hz, 1H), 2.34 (s, 3H), 2.33 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 198.4, 143.5, 141.0, 131.6, 129.7, 128.3, 126.2, 27.4, 21.5; MS (EI, 70 eV): m/z (%) 160 (14) [M+], 145 (100), 115 (48), 117 (35); Known compound30.
(E)-4-(m-Tolyl)but-3-en-2-one 3c
107.3 mg, 67%; Oil; IR (film): 3021, 2921, 1669, 1611, 1358, 1257, 977, 779, 691 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.46 (d, J = 16.8 Hz, 1H), 7.33–7.32 (m, 2H), 7.26 (t, J = 7.8 Hz, 1H), 7.18 (d, J = 7.8 Hz, 1H), 6.68 (d, J = 16.2 Hz, 1H), 2.35 (s, 6H, 2CH3); 13C NMR (150 MHz, CDCl3): δ 198.2, 143.5, 138.6, 134.4, 131.3, 128.9, 128.8, 127.0, 125.5, 27.4, 21.3; MS (EI, 70 eV): m/z (%) 161 (4) [M+ + 1], 160 (28) [M+], 145 (100), 115 (54); Known compound31.
(E)-4-(o-Tolyl)but-3-en-2-one 3d
96.1 mg, 60%; Oil; IR (film): 3057, 3022, 2964, 2926, 1824, 1670, 1612, 1360, 1257, 1176, 976, 752 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.81 (d, J = 16.2 Hz, 1H), 7.56 (d, J = 7.2 Hz, 1H), 7.28 (t, J = 7.2 Hz, 1H), 7.21 (t, J = 7.8 Hz, 2H), 6.64 (d, J = 16.2 Hz, 1H), 2.44 (s, 3H), 2.38 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 198.3, 140.8, 137.9, 133.4, 130.9, 130.2, 128.1, 126.5, 126.4, 27.8, 19.8; MS (EI, 70 eV): m/z (%) 160 (12) [M+], 145 (100), 115 (61), 117 (37), 116 (22); Known compound32.
(E)-4-(4-Methoxyphenyl)but-3-en-2-one 3e
107.5 mg, 61%; Solid, m. p. 71.2–72.3 °C (lit. 71–72 °C); IR (KBr): 3067, 3047, 2977, 2943, 2848, 1682, 1587, 1423, 1359, 1022, 989, 819 cm−1; 1H NMR (400 MHz, CDCl3, TMS): δ 7.50 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 16.4 Hz, 1H), 6.93 (d, J = 8.8 Hz, 2H), 6.63 (d, J = 16.4 Hz, 1H), 3.85 (s, 3H), 2.36 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 198.4, 161.6, 143.2, 129.9, 127.0, 125.0, 114.4, 55.3, 27.4; MS (EI, 70 eV): m/z (%) 177 (5) [M+ + 1], 176 (45) [M+], 161 (100), 133 (51); Known compound30.
(E)-4-(4-Fluorophenyl)but-3-en-2-one 3f
128.1 mg, 78%; Oil; IR (film): 3298, 1668, 1598, 1509, 1232, 1160, 1097, 977, 910, 858, 817, 778, 602 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.55–7.52 (m, 2H), 7.48 (d, J = 16.2 Hz, 1H), 7.10–7.07 (m, 2H), 6.65 (d, J = 16.2 Hz, 1H), 2.38 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 198.0, 164.0 (d, JC-F = 250.0 Hz), 141.9, 130.7 (d, JC-F = 3.5 Hz), 130.1 (d, JC-F = 8.6 Hz), 126.9 (d, JC-F = 2.3 Hz), 116.1 (d, JC-F = 21.9 Hz), 27.5; MS (EI, 70 eV): m/z (%) 165 (5) [M+ + 1], 164 (39) [M+], 149 (100), 121 (68), 101 (68); Known compound33.
(E)-4-(4-Chlorophenyl)but-3-en-2-one 3g
130.0 mg, 72%; Solid, m. p. 53.6–55.0 °C (lit. 54–55 °C); IR (KBr): 3284, 2924, 1659, 1490, 1406, 1362, 1254, 1092, 978, 808, 581 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.48–7.44 (m, 3H, 1C = C-H + 2Ar-H), 7.37 (d, J = 8.4 Hz, 2H), 6.70 (d, J = 16.8 Hz, 1H), 2.38 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 198.0, 141.8, 136.4, 133.0, 129.4, 129.3, 127.5, 27.7; MS (EI, 70 eV): m/z (%) 181 (8) [M+ + 1], 180 (27) [M+], 165 (100), 102 (53), 137 (50); Known compound34.
(E)-4-(2-Chlorophenyl)but-3-en-2-one 3h
93.9 mg, 52%; Oil; IR (film): 2994, 2925, 1770, 1670, 1609, 1374, 1244, 1177, 1052, 975, 752, 695 cm−1; 1H NMR (400 MHz, CDCl3, TMS): δ 7.94 (d, J = 16.4 Hz, 1H), 7.63 (dd, J = 1.6 Hz, J = 7.2 Hz, 1H), 7.42 (dd, J = 1.2 Hz, J = 7.6 Hz, 1H), 7.34–7.28 (m, 2H), 6.66 (d, J = 16.4 Hz, 1H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 198.4, 139.2, 135.0, 132.6, 131.3, 130.2, 129.6, 127.6, 127.2, 27.2; MS (EI, 70 eV): m/z (%) 180 (9) [M+], 145 (100), 137 (26), 101 (25), 165 (23); Known compound35.
(E)-4-(4-Bromophenyl)but-3-en-2-one 3i
159.8 mg, 71%; Solid, m. p. 81.6–82.3 °C (lit. 81–83 °C). IR (KBr): 3021, 2921, 1658, 1419, 1360, 1259, 977, 803, 699 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.53 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 16.2 Hz, 1H), 7.40 (d, J = 8.4 Hz, 2H), 6.70 (d, J = 16.2 Hz, 1H), 2.38 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 198.0, 141.9, 133.4, 132.3, 129.6, 127.6, 124.8, 27.7; MS (EI, 70 eV): m/z (%) 226 (15) [M+](81Br), 224 (15) [M+], 102 (100), 145 (55), 209 (48), 211 (46); Known compound36.
(E)-4-(4-(Trifluoromethyl)phenyl)but-3-en-2-one 3j
154.2 mg, 72%; Oil; IR (film): 2962, 2840, 1664, 1615, 1602, 1416, 1328, 1169, 1123, 978, 820 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.65 (s, 4H), 7.52 (d, J = 16.8 Hz, 1H), 6.78 (d, J = 16.2 Hz, 1H), 2.41 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 197.9, 141.3, 137.9, 131.9 (d, JC-F = 32.4 Hz), 129.1, 128.3, 125.9 (m), 123.8 (d, JC-F = 270.5 Hz), 27.9; MS (EI, 70 eV): m/z (%) 214 (21) [M+], 199 (100), 151 (84), 171 (66); Known compound13.
(E)-4-(4-Nitrophenyl)but-3-en-2-one 3k
103.2 mg, 54%; Solid, m. p. 116.1–117.7 °C (lit. 117–118 °C); IR (KBr): 3109, 3080, 2926, 1691, 1688, 1593, 1514, 1344, 1254, 1176, 1109, 982, 858, 825, 790, 748, 885 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 8.26 (d, J = 7.8 Hz, 2H), 7.70 (d, J = 7.8 Hz, 2H), 7.54 (d, J = 16.8 Hz, 1H), 6.82 (d, J = 16.2 Hz, 1H), 2.43 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 197.5, 148.6, 140.7, 140.1, 130.4, 128.8, 124.2, 28.1; MS (EI, 70 eV): m/z (%) 191 (21) [M+], 176 (100), 174 (60), 130 (58), 102 (51); Known compound30.
(E)-4-(Naphthalen-1-yl)but-3-en-2-one 3l
113.8 mg, 58%; Oil; IR (film): 3057, 3007, 2962, 2924, 1936, 1817, 1670, 1599, 1356, 1255, 1189, 974, 795, 773 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 8.35 (d, J = 16.2 Hz, 1H), 8.16 (d, J = 8.4 Hz, 1H), 7.90–7.86 (m, 2H), 7.76 (d, J = 7.2 Hz, 1H), 7.58–7.46 (m, 3H), 6.80 (d, J = 16.2 Hz, 1H), 2.45 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 198.2, 140.1, 133.7, 131.7, 131.5, 130.8, 129.6, 128.9, 127.0, 126.3, 125.5, 125.2, 123.2, 28.0; MS (EI, 70 eV): m/z (%) 197 (7) [M+ + 1], 196 (47) [M+], 153 (100), 152 (86), 195 (53), 181 (46), 151 (34); Known compound13.
(E)-4-(Pyridin-2-yl)but-3-en-2-one 3m
76.5 mg, 52%; Oil; IR (film): 3051, 3005, 2926, 2854, 1670, 1620, 1581, 1431, 1360, 1250, 980, 905, 766 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 8.66 (d, J = 4.2 Hz, 1H), 7.73 (t, J = 7.8 Hz, 1H), 7.53 (d, J = 16.2 Hz, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.30–7.29 (m, 1H), 7.14 (d, J = 16.2 Hz, 1H), 2.41 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 198.4, 153.1, 150.1, 141.9, 136.8, 130.2, 124.3, 124.2, 28.0; MS (EI, 70 eV): m/z (%) 148 (4) [M+ + 1], 147 (39) [M+], 132 (100), 104 (61), 78 (50), 51 (25), 43 (16); Known compound37.
(E)-4-(Thiophen-2-yl)but-3-en-2-one 3n
137.0 mg, 90%; Oil; IR (film): 3103, 3008, 2922, 1803, 1684, 1595, 1514, 1489, 1423, 1358, 1254, 1200, 1189, 986, 858, 818, 708 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.63 (d, J = 15.6 Hz, 1H), 7.39 (d, J = 4.2 Hz, 1H), 7.28 (d, J = 3.6 Hz, 1H), 7.07–7.05 (m, 1H), 6.52 (d, J = 16.2 Hz, 1H), 2.33 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 197.7, 139.7, 135.7, 131.5, 128.9, 128.3, 125.8, 27.7; MS (EI, 70 eV): m/z (%) 153 (5) [M+ + 1], 152 (53) [M+], 137 (100), 109 (65), 65 (27), 43 (18), 69 (13); Known compound13.
(3E,5E)-6-Phenylhexa-3,5-dien-2-one 3o
156.7 mg, 91%; Solid, m. p. 63.3–64.8 °C (lit. 64 °C); IR (KBr): 3057, 3028, 2926, 1880, 1711, 1670, 1614, 1587, 1448, 1360, 1252, 1144, 997, 750, 892 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.48 (d, J = 7.2 Hz, 2H), 7.37 (t, J = 7.2 Hz, 2H), 7.33–7.27 (m, 2H), 6.97–6.86 (m, 2H), 6.26 (d, J = 15.0 Hz, 1H), 2.32 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 198.4, 143.4, 141.3, 136.0, 130.5, 129.2, 128.9, 127.3, 126.7, 27.4; MS (EI, 70 eV): m/z (%) 173 (10) [M+ + 1], 172 (70) [M+], 128 (100), 129 (91), 157 (56), 171 (35), 95 (22); Known compound38.
(E)-4-cyclohexylbut-3-en-2-one 3p
45.8 mg, 30%, Oil; IR (film): 2927, 2853, 1675, 1624, 1449, 1359, 1254, 980cm-1; 1H NMR (600 MHz, CDCl3, TMS): δ 6.77–6.72 (m, 1 H), 6.02 (d, J = 16.2 Hz, 1H), 2.25 (s, 3H), 2.15–2.14 (m, 1 H), 1.78–1.76 (m, 4 H), 1.34–1.12 (m, 6 H); 13C NMR (150 MHz, CDCl3): δ 199.3, 153.5, 128.8, 40.6, 31.8, 26.9, 25.9, 25.7; MS (EI, 70 eV): m/z (%) 152 (49) [M+], 94 (100), 109 (70), 83 (80). Known compound39.
(E)-Chalcone 3q
147.9 mg, 71%; Solid, m. p. 55.3–56.8 °C (lit. 55–56 °C); IR (KBr): 3060, 3027, 2974, 2897, 1962, 1903, 1813, 1664, 1606, 1494, 1336, 1307, 1286, 1215, 1016, 980, 748 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 8.01 (s, 2H), 7.80 (d, J = 15.6 Hz, 1H), 7.62 (s, 2H), 7.55–7.48 (m, 4H), 7.39 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 190.6, 144.9, 138.3, 134.9, 132.8, 130.6, 129.0, 128.7, 128.5, 128.5, 122.1; MS (EI, 70 eV): m/z (%) 208 (55) [M+], 207 (100), 77 (70), 45 (36), 103 (31), 131 (27); Known compound29.
(E)-3-Phenyl-1-p-tolylprop-2-en-1-one 3r
135.6 mg, 61%; Solid, m. p. 73.7–75.1 °C (lit. 75 oC); IR (KBr): 3028, 2921, 1662, 1609, 1494, 1449, 1334, 1304, 1223, 1180, 1034, 980, 820, 760 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.95 (d, J = 8.4 Hz, 2H), 7.82 (d, J = 15.6 Hz, 1H), 7.65–7.67 (m, 2H), 7.55 (d, J = 15.6 Hz, 1H), 7.42 (t, J = 7.2 Hz, 3H), 7.31 (d, J = 7.8 Hz, 2H), 2.45 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 190.0, 144.4, 143.7, 135.7, 135.0, 130.5, 129.4, 129.0, 128.7, 128.4, 122.1, 21.7; MS (EI, 70 eV): m/z (%) 223 (9) [M+ + 1], 222 (62) [M+], 221 (100), 45 (47), 91 (41), 119 (40), 77 (27); Known compound40.
(E)-1-(4-Chlorophenyl)-3-phenylprop-2-en-1-one 3s
165.0 mg, 68%; Solid, m. p. 92.7–93.8 °C (lit. 90–92 °C); IR (KBr): 1661, 1601, 1448, 1399, 1218, 1090, 982, 829, 762 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.95 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 15.6 Hz, 1H), 7.62–7.64 (m, 2H), 7.49–7.46 (m, 3H), 7.40–7.42 (m, J = 6.6 Hz, 3H); 13C NMR (150 MHz, CDCl3): δ 189.2, 145.4, 139.3, 136.5, 134.7, 130.8, 129.9, 129.0, 128.9, 128.6, 121.5; MS (EI, 70 eV): m/z (%) 244 (18) [M+](37Cl), 243 (39) [M+ + 1], 241 (100), 242 (58), 207 (51); Known compound41.
(E)-1-Phenylhept-1-en-3-one 3t
101.7 mg, 54%; Oil; IR (film): 3060, 3028, 2958, 2931, 2872, 1690, 1663, 1611, 1576, 1495, 1450, 1331, 1181, 1130, 978, 749, 691cm-1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.45 (d, J = 16.00 Hz, 1H), 7.42–7.45 (m, 2H), 7.28–7.29 (m, 3H), 6.63 (d, J = 16.2 Hz), 2.56 (t, J = 7.5 Hz, 2H), 1.54–1.59 (m, 2H), 1.26–1.32 (m, 2H), 0.85 (t, J = 7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3): δ 199.6, 141.2, 133.5, 129.3,127.9, 127.2, 125.2, 39.6, 25.4, 21.4, 12.9; MS (EI, 70 eV): m/z (%) 188 (11) [M+], 131 (100); Known compound42.
(E)-5-methyl-1-phenylhex-1-en-3-one 3u
113.0 mg, 60%; Oil; IR (film): 3061, 3028, 2957, 2871, 1688, 1657, 1610, 1576, 1450, 1366, 1189, 1061, 977, 749, 691 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.43 (m, 3H), 7.28–7.27 (m, 3H),6.63 (d, J = 16.2 Hz, 1H), 2.43 (d, J = 6.6Hz, 2H), 2.11–2.12 (m, 1H), 0.88 (d, J = 6.6 Hz, 6H); 13C NMR (150 MHz, CDCl3): δ 199.2, 141.3, 133.4, 129.4, 127.9, 127.2, 125.5, 48.8, 24.2, 21.7; MS (EI, 70 eV): m/z (%) 188 (11) [M+], 131 (100); Known compound43.
(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one 4a
196.8 mg, 84%; Solid, m. p. 120.6–121.9 °C (lit. 120–122 °C); IR (KBr): 3053, 3026, 1651, 1592, 1194, 982, 762 cm−1; 1H NMR (400 MHz, CDCl3, TMS): δ 7.75 (d, J = 16.0 Hz, 2H), 7.63 (m, 4H), 7.42 (m, 6H), 7.09 (d, J = 16.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 188.9, 143.3, 134.7, 130.5, 128.9, 128.4, 125.4; MS (EI, 70 eV): m/z (%) 234 (38) [M+], 235 (7) [M+ + 1], 103 (100), 131 (59), 77 (40), 233 (34).Known compound44.
(1E,4E)-1,5-di-p-tolylpenta-1,4-dien-3-one 4b
102.3 mg, 39%; Solid, m. p. 172.6–173.9 °C (lit. 174–176 °C).IR (KBr): 3025, 2921, 2850, 1652, 1593, 1111, 1068, 981, 695 cm−1; 1H NMR (400 MHz, CDCl3, TMS): δ 7.72 (d, J = 16.0 Hz, 2H), 7.52 (d, J = 8.0 Hz, 4H), 7.22 (d, J = 8.0 Hz, 4H), 7.03 (d, J = 16.0 Hz, 2H), 2.39 (s, 6H); 13C NMR (100 MHz, CDCl3): δ 189.1, 143.2,140.9, 132.1, 129.7, 128.4, 124.5, 21.5; MS (EI, 70 eV): m/z (%) 262 (27) [M+], 115 (100), 117 (49), 83 (45), 91 (44); Known compound45.
(1E,4E)-1,5-Bis(4-methoxyphenyl)penta-1,4-dien-3-one 4c
92.3 mg, 31%; Solid, m. p. 119.3–120.7 °C (lit. 119–120 °C); IR (KBr): 2930, 2836, 1647, 1600, 1511, 1254, 1171, 1094, 1029, 984, 830, 777, 690 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.70 (d, J = 15.6 Hz, 2H), 7.57 (d, J = 8.4 Hz, 4H), 6.96 (d, J = 15.6 Hz, 2H), 6.93 (d, J = 8.4 Hz, 4H), 3.85 (s, 6H); 13C NMR (150 MHz, CDCl3): δ 188.8, 161.6, 142.6, 130.1, 127.7, 123.6, 114.4, 55.4; MS (EI, 70 eV): m/z (%) 294 (87) [M+], 186 (100), 133 (99), 161 (73), 118 (53); Known compound44.
(1E,4E)-1,5-Bis(4-fluorophenyl)penta-1,4-dien-3-one 4d
210.8 mg, 78%; Solid, m. p. 151.6–153.2 °C (lit. 152 °C); IR (KBr): 2956, 2924, 2853, 1652, 1507, 980, 831 cm−1; 1H NMR (400 MHz, CDCl3, TMS): δ 7.68 (d,J = 16.0, 2H), 7.59–7.56 (m, 4H), 7.10–7.00(m, 4H), 6.98 (d, J = 16.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 188.4, 164.0 (d, JC-F = 250.6 Hz), 142.0, 130.9 (d, JC-F = 3.3 Hz), 130.3 (d, JC-F = 8.4 Hz), 125.0 (d, JC-F = 2.3 Hz), 116.1 (d, JC-F = 21.8 Hz); MS (EI, 70 eV): m/z (%) 270 (38) [M+], 101 (100), 121 (80), 149 (55), 109 (50); Known compound46.
(1E,4E)-1,5-Bis(4-(trifluoromethyl)phenyl)penta-1,4-dien-3-one 4e
340.7 mg, 92%; Solid, m. p.128.9–129.7 °C (lit. 129–130 °C); IR (KBr): 1653, 1601, 1575, 981 cm−1; 1H NMR (400 MHz, CDCl3, TMS): δ 7.78–7.67 (m, 10H), 7.14 (d, J = 16.0 Hz. 2H); 13C NMR (100 MHz, CDCl3): δ 188.1, 141.9, 137.9, 132.2, 131.9, 128.5, 127.1, 125.9(m); MS (EI, 70 eV): m/z (%) 370 (36) [M+], 151 (100), 199 (60), 171 (58), 301 (37), 102 (31); Known compound44.
(1E,4E)-1,5-Di(thiophen-2-yl)penta-1,4-dien-3-one 4f
152.7 mg, 62%; Solid, m. p. 113.3–114.2 °C (lit. 113–114 °C). IR (KBr): 2955, 2923, 2870, 1603, 1141, 702 cm−1; 1H NMR (400 MHz, CDCl3, TMS): δ 7.75 (d, J = 15.6 Hz, 2H), 7.31 (d, J = 5.2 Hz, 2H), 7.23 (d, J = 3.6 Hz, 2H), 6.98 (t, J = 4.4 Hz, 2H), 6.73 (d, J = 15.6 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 187.6, 140.3,135.6, 131.8, 128.8, 128.3, 124.4; MS (EI, 70 eV): m/z (%) 246 (39) [M+], 109 (100), 97 (59), 137 (42), 162 (40); Known compound47.
(1E,4E)-1,5-Di(furan-2-yl)penta-1,4-dien-3-one 4g
171.4, 80%; Solid m. p. 58.8–59.9 °C (lit. 59–60 °C); IR (KBr): 2987, 2869, 1792, 1759, 1649, 1619, 1595, 1141, 1016, 747 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.51 (s, 2H), 7.49 (d, J = 15.6 Hz, 2H), 6.93 (d, J = 15.6 Hz, 2H), 6.68 (s, 2H), 6.49 (s, 2H); 13C NMR (150 MHz, CDCl3): δ 188.1, 151.5, 144.9, 129.2, 123.2, 115.9, 112.6; MS (EI, 70 eV): m/z (%) 214 (100) [M+], 215 (14) [M+ + 1], 121 (60), 129 (44); Known compound48.
(1E,4E)-1-Phenyl-5-(p-tolyl)penta-1,4-dien-3-one 4h
168.8 mg, 68%; Solid, m. p. 107.5–108.7 °C (lit. 107–108 °C); IR (KBr): 3025, 2956, 2924, 2854, 1652, 1617, 1449, 1336, 1179, 1095, 979 cm−1; 1H NMR (400 MHz, CDCl3, TMS): δ 7.75 (d, J = 3.2 Hz, 1H), 7.71 (d, J = 3.2 Hz, 1H), 7.61 (d, J = 4.0 Hz, 2H), 7.51 (d, J = 8.0 Hz, 2H), 7.41 (s, 3H), 7.22 (d, J = 8.0 Hz, 2H), 7.11–7.03 (m, 2H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 188.9, 143.4, 143.0, 141.0, 134.8, 132.0, 130.4, 129.7, 128.9, 128.4, 128.3, 125.4, 124.5, 21.5; MS (EI, 70 eV): m/z (%) 248 (51) [M+], 115 (100), 233 (79), 103 (67), 91 (64); Known compound49.
(1E,4E)-1-(4-Methoxyphenyl)-5-phenylpenta-1,4-dien-3-one 4i
137.4 mg, 52%; Solid, m. p.88.0–89.2 °C (lit. 85–89 °C); IR (KBr): 2956, 2924, 2851, 1651, 1601, 1509, 1458, 1251, 1171 cm−1; 1H NMR (400 MHz, CDCl3, TMS): δ 7.75–7.69 (m, 2H), 7.63–7.60 (m, 2H), 7.59–7.56 (m, 2H), 7.42–7.39 (m, 3H), 7.078 (d, J = 16.0 Hz, 1H), 6.95 (t, J = 12.2 Hz, 3H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 188.9, 161.6, 143.2, 142.8, 134.9, 130.4, 130.2, 128.9, 128.3, 127.5, 125.5, 123.3, 114.4, 55.4; MS (EI, 70 eV): m/z (%) 264 (100) [M+], 108 (99), 103 (97), 97 (66), 83 (64), 98 (61); Known compound45.
(1E,4E)-1-(4-Fluorophenyl)-5-phenylpenta-1,4-dien-3-one 4j
204.4 mg, 81%; Solid, m. p. 112.8–113.2 °C; IR (KBr): 2955, 2923, 2852, 1651, 1587, 1507, 982, 826, 756 cm−1; 1H NMR (400 MHz, CDCl3, TMS): δ 7.71 (t,J = 15.6, 2H), 7.61–7.57 (m, 4H), 7.39 (t, J = 3.2, 3H), 7.10–7.06 (m, 2H), 7.02 (d, J = 5.6Hz, 1H), 6.98 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 188.7, 164.0 (d, JC-F = 250.5 Hz), 143.4, 141.9, 134.7, 130.9 (d, JC-F = 3.3 Hz), 130.6, 130.3 (d, JC-F = 8.4 Hz), 128.9, 128.4, 125.4, 125.0 (d, JC-F = 2.2 Hz), 116.1 (d, JC-F = 21.8 Hz); MS (EI, 70 eV): m/z (%) 252 (84) [M+], 101 (100), 103 (88), 251 (73), 121 (59); Known compound50.
(1E,4E)-1-Phenyl-5-(4-(trifluoromethyl)phenyl)penta-1,4-dien-3-one 4k
278.1 mg, 92%; Solid, m. p. 142.4–143.2 °C (lit. 142–143 °C); IR (KBr): 1652, 1593, 1324, 1110, 1068, 981, 826, 760, 695 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.76 (d, J = 16.8 Hz, 1H), 7.70–7.62 (m, 5H), 7.42 (s, 2H), 7.35 (d, J = 15.6 Hz, 3H), 7.14 (d, J = 15.6 Hz, 1H), 7.07 (d, J = 15.6 Hz, 1H); 13C NMR (150 MHz, CDCl3): δ 188.5, 144.0, 141.2, 138.3, 134.6, 130.8, 129.0, 128.9, 128.5 (d, JC-F = 4.2 Hz), 128.4, 127.4 (t, JC-F = 35.9 Hz), 125.9 (m), 125.3, 124.8 (m); MS (EI, 70 eV): m/z (%) 302 (56) [M+], 103 (100), 97 (82), 83 (73), 131 (73), 98 (73); Known compound51.
(1E,4E)-1-Phenyl-5-(thiophen-2-yl)penta-1,4-dien-3-one 4l
163.4, 68%; Solid, m. p. 87.8–88.9 °C; IR (KBr): 3306, 3217, 2988, 2870, 1648, 1612, 1577, 1392, 1141, 1096, 974, 854, 755 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.87 (d, J = 15.0 Hz, 1H), 7.72 (d, J = 16.2 Hz, 1H), 7.60 (s, 2H), 7.40 (s, 4H), 7.33 (s, 1H), 7.07 (s, 1H), 7.02 (d, J = 15.6 Hz, 1H), 6.89 (d, J = 15.6 Hz, 1H); 13C NMR (150 MHz, CDCl3): δ 188.3, 143.2, 140.3, 135.8, 134.8, 131.8,130.5, 128.9, 128.8, 128.4, 128.3, 125.6, 124.3; MS (EI, 70 eV): m/z (%) 240 (98) [M+], 109 (100), 97 (96), 103 (95), 211 (63), 128 (62), 137 (59); Known compound52.
(1E,4E)-1-Phenyl-5-(2-furyl)penta-1,4-dien-3-one 4m
179.4 mg, 80%; Oil; IR (film): 3120, 3059, 2988, 2869, 1650, 1619, 1449, 1335, 1017, 977, 750 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.72 (d, J = 16.2 Hz, 1H), 7.60 (s, 2H), 7.52 (d, J = 15.0 Hz, 2H), 7.39 (s, 3H), 7.01 (s, 1H), 6.99 (s, 1H), 6.70 (s, 1H), 6.50 (s, 1H); 13C NMR (150 MHz, CDCl3): δ 188.6, 151.6, 144.9, 143.1, 134.9, 130.5, 129.5, 128.9, 128.4, 126.1, 122.5, 116.0, 112.7; MS (EI, 70 eV): m/z (%) 224 (100) [M+], 131 (97), 103 (89), 167 (61), 121 (53), 83 (52); Known compound52.
(1E,4E)-1-Cyclohexyl-5-phenylpenta-1,4-dien-3-one 4n
Solid, m. p. 44.5–46.2 °C (lit. 42–46 °C); IR (KBr): 2926, 2852, 1659, 1627, 1600 cm−1; 1H NMR (600 MHz, CDCl3, TMS): δ 7.55 (d, J = 15.6 Hz, 1H), 7.49 (s, 2H), 7.29 (s, 3H), 6.91–6.84 (m, 2H), 6.29 (d, J = 15.6 Hz, 1H), 2.12 (d, J = 3.0 Hz, 1H), 1.74–1.59 (m, 5H), 1.27–1.09 (m, 5H); 13C NMR (150 MHz, CDCl3): δ 189.8, 153.2, 142.9, 134.9, 130.3, 128.9, 128.3, 126.9, 124.9, 40.9, 31.9, 25.9, 25.8; MS (EI, 70 eV): m/z (%) 240 (21) [M+], 131 (100), 103 (44); Known compound53.
Additional Information
How to cite this article: Yu, L. et al. Ca(OH)2-Catalyzed Condensation of Aldehydes with Methyl ketones in Dilute Aqueous Ethanol: A Comprehensive Access to a,β-Unsaturated Ketones. Sci. Rep. 6, 30432; doi: 10.1038/srep30432 (2016).
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Acknowledgements
This work was supported by NNSFC (21202141), Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions, Yangzhou Nature Science Foundation (YZ2014040), the Innovation Foundation of Yangzhou University (2015CXJ009), the High Level Talent Support Project of Yangzhou University, the Opening Foundation of the Key Laboratory of Environmental Materials and Engineering of Jiangsu Province (K14010) and the Open Project Program of Jiangsu Key Laboratory of Zoonosis (R1509). We thank the analysis centre of Yangzhou University for assistances.
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L.Y. supervised the overall project. M.H., J.L. and L.X. performed the experiments. L.Y., Y.D. and Q.X. designed the experiments.
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Yu, L., Han, M., Luan, J. et al. Ca(OH)2-Catalyzed Condensation of Aldehydes with Methyl ketones in Dilute Aqueous Ethanol: A Comprehensive Access to α,β-Unsaturated Ketones. Sci Rep 6, 30432 (2016). https://doi.org/10.1038/srep30432
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DOI: https://doi.org/10.1038/srep30432
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