* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Reference：
[1] Advanced Synthesis and Catalysis, 2008, vol. 350, # 17, p. 2740 - 2746
[2] Synlett, 2010, # 9, p. 1351 - 1354
[3] Synthetic Communications, 2004, vol. 34, # 20, p. 3801 - 3806
[4] Journal of Heterocyclic Chemistry, 2008, vol. 45, # 3, p. 853 - 857
[5] Turkish Journal of Chemistry, 2014, vol. 38, # 4, p. 650 - 660
2
[ 108-94-1 ]
[ 109-77-3 ]
[ 4354-73-8 ]
Yield
Reaction Conditions
Operation in experiment
100%
at 25℃; for 2 h;
The corresponding reactions (a) to (p) have been achieved through reactions, under agitation and in 5 ml of solvent (dimethylformamide(ine?) DMF or acetonitril MeCN), of 1 millimole of carbonyl compound and 1 millimole of activated methanol, in the presence of 0.0035 g of 'HDT-F' catalyst prepared in example 1. In each case, the progress of the reaction was followed by chromatography on a plate. At the end of the reaction the catalyst was filtered, the filtrate was washed with water and the product was extracted by sodium sulphate and concentrated under low pressure. The indicated yield was calculated on the basis of NMR spectra observed at the final medium, on the basis of R1R2CO ketonic compounds quantity consumed during the reaction.
93%
With C8H18NO3(1+)*C2H4NO2(1-) In water at 20℃;
General procedure: A mixture of carbonyl compound (0.5 mmol), activated methylene compound (0.5 mmol), IL catalyst (10 mol percent) and water (1 mL) was stirred at room temperature in 25-mL round bottomed flask. Upon completion of the reaction (monitored by TLC), the reaction mixture always solidified in the round bottomed flask. Then the solidified mixture was filtered and washed with cold water (5 mL) to remove the IL catalyst, and evaporated under reduced pressure to obtain the target products. The products of 3o, 3p, 3q, 3x, 3c’, 3d’ are colourless oil, and they were purified by column chromatography on silica gel using petroleum ether/ethyl acetate as the eluent after the solvent was removed under reduced pressure. The products of 3j’, 3k’were prepared under solvent-free condition; After completion of the reaction, the solidified mixture was washed with ethanol (5 mL) to remove the IL catalyst, and evaporated under reduced pressure to obtain the target products.
90%
With C9H20NO2(1+)*C2H3O2(1-) In water at 25℃; for 20 h; Green chemistry
General procedure: A mixture of activated methylene compound 4 (0.5 mmol), carbonyl compound 5 (0.5 mmol), IL catalyst (10 mol percent) and water (1 mL) was stirred at room temperature in a 25 mL round bottomed flask. Upon completion of the reaction (monitored by TLC), the reaction mixture always solidified in the round bottomed flask. Then the solidified mixture was filtered and washed with cold water (5 mL) to remove the IL catalyst, and evaporated under reduced pressure to obtain the target products 6. The produce of 6l were purified by column chromatography on silica gel using petroleum ether/ethyl acetate (8:1) as the eluent and got pure product after the solvent was removed under reduced pressure.
89%
With 1,4-diaza-bicyclo[2.2.2]octane In water at 20℃; for 0.116667 h; Green chemistry
General procedure: A mixture of 1a (232 mg, 2.0 mmol) and 2a (132 mg, 2.0 mmol) in H2O (0.5 mL) and DABCO (224 mg, 2.0mmol) was stirred at room temperature for 3 min until TLC showed complete disappearance of the starting materials. The mixture was extracted by EtOAc (5 mL) and the organic layer was washed with saturated solution of NaHCO3 and brine. The organic layer was dried over Na2SO4 . Product 3aa was obtained by evaporation of the volatile portion of the organic layer and was puried by recrystallization from EtOAc/hexane mixture. Product 3aa was obtained in 80percent yield (262 mg). The product was identied based on its physical and spectral characteristics. The remaining compounds 3ab-3db were synthesized in a similar manner.
82%
With Fe3O4(at)SiO2-N1-(3-trimethoxysilylpropyl)diethylenetriamine nanoparticles catalyst In water at 75℃; for 3 h;
General procedure: A mixture of the aldehyde/ketone (0.1 mmol), compound of active methylene group (0.1 mmol), catalyst (5 mg)and solvent (toluene or water, 0.4 mL) was added in a glass tube and mechanically stirred at 75 °C. The reaction progress was monitored by Gas Cromatography with FID detector. After the completion of this reaction, the catalyst was removed by magnetic separation. For there actions in toluene, the mixture was purified by using column chromatography, and for the reactions in water, the product was precipitated with cool water, filtrated and dried under low pressure. All the products were characterized by 1H NMR, and 13C NMR.
60%
With triethylamine In ethanol for 0.5 h; Reflux
A mixture of 1 mmol of cyclohexanone, 1 mmol of malonic acid dinitrile, and 0.08 mol percent of triethylamine in ethyl alcohol was refluxed for 30 min. The crystals were filtered off, washed with cold ethanol, and dried in air. Yield 0.40 g (60percent), mp 172–174°C (mp 173.5–174.5°C[6]). Found, percent: C 72.99; H 6.93; N 19.79. C9H10N2. Calculated: C 73.79; H 6.85; N 19.27.
Reference：
[1] Patent: US2005/250963, 2005, A1, . Location in patent: Page/Page column 5
[2] Green Chemistry, 2010, vol. 12, # 3, p. 514 - 517
[3] Synlett, 2000, # 7, p. 1016 - 1018
[4] Collection of Czechoslovak Chemical Communications, 2005, vol. 70, # 10, p. 1727 - 1736
[5] European Journal of Organic Chemistry, 2008, # 28, p. 4763 - 4768
[6] RSC Advances, 2013, vol. 3, # 45, p. 23075 - 23079
[7] Russian Chemical Bulletin, 2013, vol. 62, # 3, p. 683 - 686[8] Izv. Akad. Nauk, Ser. Khim., 2013, # 3, p. 682 - 685,4
[9] Journal of the Chinese Chemical Society, 2013, vol. 60, # 3, p. 288 - 292
[10] New Journal of Chemistry, 2016, vol. 40, # 8, p. 6970 - 6976
[11] Applied Catalysis A: General, 2014, vol. 475, p. 140 - 146
[12] Asian Journal of Chemistry, 2012, vol. 24, # 2, p. 653 - 656
[13] Angewandte Chemie - International Edition, 2017, vol. 56, # 28, p. 8125 - 8129[14] Angew. Chem., 2017, vol. 129, # 28, p. 8237 - 8241,5
[15] Tetrahedron Letters, 2017, vol. 58, # 24, p. 2360 - 2365
[16] Tetrahedron Letters, 2004, vol. 45, # 15, p. 3055 - 3058
[17] Green Chemistry, 2009, vol. 11, # 6, p. 863 - 867
[18] Journal of Materials Chemistry A, 2014, vol. 2, # 33, p. 13422 - 13430
[19] Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences, 2014, vol. 69, # 5, p. 509 - 518
[20] Synthetic Communications, 2018, vol. 48, # 9, p. 1060 - 1067
[21] Turkish Journal of Chemistry, 2014, vol. 38, # 4, p. 650 - 660
[22] Tetrahedron Letters, 1992, vol. 33, # 49, p. 7535 - 7538
[23] Chemistry Letters, 2000, # 9, p. 998 - 999
[24] Organic Letters, 2018, vol. 20, # 7, p. 1970 - 1973
[25] Russian Journal of Organic Chemistry, 2000, vol. 36, # 12, p. 1703 - 1708
[26] Catalysis Letters, 2017, vol. 147, # 1, p. 167 - 180
[27] Angewandte Chemie - International Edition, 2016, vol. 55, # 51, p. 15792 - 15796[28] Angew. Chem., 2016, vol. 128, # 51, p. 16024 - 16028,5
[29] Journal of the American Chemical Society, 1989, vol. 111, # 15, p. 5954 - 5955
[30] Journal of the American Chemical Society, 1995, vol. 117, # 50, p. 12436 - 12451
[31] Tetrahedron Letters, 2004, vol. 45, # 39, p. 7291 - 7295
[32] Synthetic Communications, 2006, vol. 36, # 22, p. 3441 - 3445
[33] Organic Preparations and Procedures International, 2007, vol. 39, # 1, p. 71 - 75
[34] Zeitschrift fur Naturforschung - Section B Journal of Chemical Sciences, 1999, vol. 54, # 4, p. 541 - 543
[35] Synthesis, 1980, # 4, p. 296 - 299
[36] Organic Letters, 2013, vol. 15, # 20, p. 5298 - 5301
[37] Tetrahedron Letters, 1996, vol. 37, # 7, p. 1113 - 1116
[38] Russian Journal of General Chemistry, 2017, vol. 87, # 10, p. 2477 - 2480[39] Zh. Obshch. Khim., 2017, vol. 87, # 10, p. 1728 - 1731,4
[40] Bulletin of the Chemical Society of Japan, 1983, vol. 56, # 6, p. 1885 - 1886
[41] Journal of Organic Chemistry, 1984, vol. 49, # 26, p. 5195 - 5197
[42] RSC Advances, 2015, vol. 5, # 99, p. 81415 - 81428
[43] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2001, vol. 40, # 5, p. 391 - 393
[44] Journal of Heterocyclic Chemistry, 2014, vol. 51, # 6, p. 1785 - 1790
[45] Journal of the American Chemical Society, 1941, vol. 63, p. 733
[46] Canadian Journal of Chemistry, 1963, vol. 41, p. 2905
[47] Tetrahedron, 1974, vol. 30, # 16, p. 2949 - 2959
[48] Journal of Organic Chemistry, 1966, vol. 31, p. 2784 - 2789
[49] Journal of Organic Chemistry, 1961, vol. 26, p. 4874 - 4878
[50] Journal of Organic Chemistry, 1967, vol. 32, p. 2372 - 2375
[51] Sov. Prog. Chem. (Engl. Transl.), 1975, vol. 41, # 7, p. 85 - 86[52] Ukrainskii Khimicheskii Zhurnal (Russian Edition), 1975, vol. 41, # 7, p. 762 - 764
[53] Phosphorus, Sulfur and Silicon and the Related Elements, 1993, vol. 82, # 1-4, p. 91 - 98
[54] Chemical Communications (Cambridge, United Kingdom), 1998, # 9, p. 1033 - 1034
[55] Journal of the American Chemical Society, 2003, vol. 125, # 38, p. 11460 - 11461
[56] Synthetic Communications, 2004, vol. 34, # 20, p. 3801 - 3806
[57] Synthesis, 2005, # 4, p. 543 - 546
[58] Chemistry - A European Journal, 2006, vol. 12, # 32, p. 8228 - 8239
[59] Organic and Biomolecular Chemistry, 2006, vol. 4, # 9, p. 1641 - 1646
[60] Journal of Heterocyclic Chemistry, 2008, vol. 45, # 3, p. 853 - 857
[61] European Journal of Organic Chemistry, 2008, # 6, p. 975 - 993
[62] Tetrahedron Letters, 2009, vol. 50, # 34, p. 4833 - 4837
[63] Green Chemistry, 2009, vol. 11, # 4, p. 526 - 530
[64] Chemical Communications, 2011, vol. 47, # 7, p. 2053 - 2055
[65] Synthetic Communications, 2011, vol. 41, # 10, p. 1410 - 1420
[66] Catalysis Communications, 2011, vol. 12, # 13, p. 1212 - 1217
[67] Patent: US2012/122888, 2012, A1, . Location in patent: Page/Page column 45
[68] Chemistry - An Asian Journal, 2013, vol. 8, # 10, p. 2459 - 2465
[69] RSC Advances, 2014, vol. 4, # 13, p. 6447 - 6453
[70] Australian Journal of Chemistry, 2013, vol. 66, # 8, p. 913 - 920
[71] European Journal of Medicinal Chemistry, 2014, vol. 85, p. 450 - 457
[72] Journal of Molecular Catalysis B: Enzymatic, 2014, vol. 109, p. 170 - 177
[73] Journal of Catalysis, 2014, vol. 317, p. 1 - 10
[74] Chemical Science, 2014, vol. 5, # 11, p. 4517 - 4524
[75] Catalysis Communications, 2015, vol. 68, p. 25 - 30
[76] Research on Chemical Intermediates, 2015, vol. 41, # 6, p. 3389 - 3400
[77] European Journal of Inorganic Chemistry, 2015, vol. 2015, # 28, p. 4699 - 4707
[78] Chemistry - A European Journal, 2015, vol. 21, # 42, p. 14862 - 14870
[79] Organic Letters, 2016, vol. 18, # 3, p. 428 - 431
[80] Angewandte Chemie - International Edition, 2016, vol. 55, # 31, p. 9060 - 9064[81] Angew. Chem., 2016, vol. 128, p. 9206 - 9210,5
[82] Monatshefte fur Chemie, 2016, vol. 147, # 7, p. 1243 - 1249
[83] Molecules, 2016, vol. 21, # 12,
[84] Polymer, 2017, vol. 112, p. 342 - 350
[85] Molecular Catalysis, 2018, vol. 453, p. 93 - 99
[86] Green Chemistry, 2018, vol. 20, # 23, p. 5336 - 5345
3
[ 177-10-6 ]
[ 109-77-3 ]
[ 4354-73-8 ]
Reference：
[1] Journal of the American Chemical Society, 2005, vol. 127, # 27, p. 9674 - 9675
4
[ 108-94-1 ]
[ 105-53-3 ]
[ 4354-73-8 ]
Reference：
[1] European Journal of Organic Chemistry, 2006, # 16, p. 3767 - 3770
5
[ 1885-23-0 ]
[ 110-82-7 ]
[ 4354-73-8 ]
Reference：
[1] Journal of the American Chemical Society, 1958, vol. 80, p. 2775,2777
6
[ 108-93-0 ]
[ 4354-73-8 ]
Reference：
[1] Polymer, 2017, vol. 112, p. 342 - 350
hydrotalcite structure integrating fluoride ions; In DMF (N,N-dimethyl-formamide); at 25℃; for 2h;Conversion of starting material;
The corresponding reactions (a) to (p) have been achieved through reactions, under agitation and in 5 ml of solvent (dimethylformamide(ine?) DMF or acetonitril MeCN), of 1 millimole of carbonyl compound and 1 millimole of activated methanol, in the presence of 0.0035 g of ?HDT-F? catalyst prepared in example 1. In each case, the progress of the reaction was followed by chromatography on a plate. At the end of the reaction the catalyst was filtered, the filtrate was washed with water and the product was extracted by sodium sulphate and concentrated under low pressure. The indicated yield was calculated on the basis of NMR spectra observed at the final medium, on the basis of R1R2CO ketonic compounds quantity consumed during the reaction.
98.0%
With 5% active carbon-supported ruthenium; In ethanol; at 78℃; for 12h;
To the reaction flask, add 4.908g (50mmol) of cyclohexanone (I-1), 0.5g (Ru molar amount is (I-1) 5 ?)Ru / C catalyst, 3.303g (50mmol) of malononitrile II and 100mL of ethanol,Stir the reaction at 78 for 12h, and check the raw material reaction by GC-MSCompletely, stop the reaction.The reaction solution is filtered once to obtain a filtrate and a filter cake,Wash the filter cake once with 5mL of ethanol and then perform secondary filtration to obtain a secondary filter cake and secondary filtrate.The secondary filter cake is the Ru / C catalyst, which can be used for the next batch of reactions;Combine the primary filtrate and the secondary filtrate through a rotary evaporator to recover ethanol (available for the next batch of reactions) and obtain a liquid at the same timeProduct 7.163g, yield 98.0%, GC-MS purity 99.0%.
96%
With Zn(1+)*C5H8NO2(1-); In water; at 80℃; for 0.166667h;
General procedure: Preparation of the general method:Take aldehyde or ketone 5.0mmol, malononitrile 5.0mmolAdd to water (5mL),Add under stirringUrgeChemical agentProline---0.01mmol,It was then heated to 80 degrees Celsius and stirred for 10 min.The reaction solution was cooled to room temperature.Filtration gave the product.
95%
With ammonium acetate; acetic acid; In benzene; at 130℃;Dean-Stark;
General procedure: The ketone, malonate derivative (1.1 equivalents), 23 ammonium acetate (0.5 equivalents), and 24 acetic acid (1 equivalent) were dissolved in 25 benzene (1.0 M with respect to the ketone) and refluxed at 130 C. using a Dean-Stark apparatus. When the ketone was fully consumed (monitored by TLC, 4-16 hrs.), the reaction mixture was cooled to room temperature and solvent was evaporated. The crude product was then filtered through a silica plug and then concentrated under vacuum. The pure products were isolated via column chromatography (hexane-ethyl acetate) unless otherwise noted. Using the foregoing method, compounds 1a-1f and 1l-1m were prepared, and are described in further detail herein below. The compound was isolated as a colorless Oil, 95% yield, 7.07 g; and purified using 10% 26 EtOAc in 27 hexane; Rf=0.3 (10% EtOAc in hex). Analytical data were consistent with that in the reference (Longstreet, A. R., et al., Org. Lett. 2013, 15 (20), 5298).
93%
With C8H18NO3(1+)*C2H4NO2(1-); In water; at 20℃;
General procedure: A mixture of carbonyl compound (0.5 mmol), activated methylene compound (0.5 mmol), IL catalyst (10 mol %) and water (1 mL) was stirred at room temperature in 25-mL round bottomed flask. Upon completion of the reaction (monitored by TLC), the reaction mixture always solidified in the round bottomed flask. Then the solidified mixture was filtered and washed with cold water (5 mL) to remove the IL catalyst, and evaporated under reduced pressure to obtain the target products. The products of 3o, 3p, 3q, 3x, 3c?, 3d? are colourless oil, and they were purified by column chromatography on silica gel using petroleum ether/ethyl acetate as the eluent after the solvent was removed under reduced pressure. The products of 3j?, 3k?were prepared under solvent-free condition; After completion of the reaction, the solidified mixture was washed with ethanol (5 mL) to remove the IL catalyst, and evaporated under reduced pressure to obtain the target products.
90%
With C9H20NO2(1+)*C2H3O2(1-); In water; at 25℃; for 20h;Green chemistry;
General procedure: A mixture of activated methylene compound 4 (0.5 mmol), carbonyl compound 5 (0.5 mmol), IL catalyst (10 mol %) and water (1 mL) was stirred at room temperature in a 25 mL round bottomed flask. Upon completion of the reaction (monitored by TLC), the reaction mixture always solidified in the round bottomed flask. Then the solidified mixture was filtered and washed with cold water (5 mL) to remove the IL catalyst, and evaporated under reduced pressure to obtain the target products 6. The produce of 6l were purified by column chromatography on silica gel using petroleum ether/ethyl acetate (8:1) as the eluent and got pure product after the solvent was removed under reduced pressure.
89%
With 1,4-diaza-bicyclo[2.2.2]octane; In water; at 20℃; for 0.116667h;Green chemistry;
General procedure: A mixture of 1a (232 mg, 2.0 mmol) and 2a (132 mg, 2.0 mmol) in H2O (0.5 mL) and DABCO (224 mg, 2.0mmol) was stirred at room temperature for 3 min until TLC showed complete disappearance of the starting materials. The mixture was extracted by EtOAc (5 mL) and the organic layer was washed with saturated solution of NaHCO3 and brine. The organic layer was dried over Na2SO4 . Product 3aa was obtained by evaporation of the volatile portion of the organic layer and was puried by recrystallization from EtOAc/hexane mixture. Product 3aa was obtained in 80% yield (262 mg). The product was identied based on its physical and spectral characteristics. The remaining compounds 3ab-3db were synthesized in a similar manner.
82%
With Fe3O4(at)SiO2-N1-(3-trimethoxysilylpropyl)diethylenetriamine nanoparticles catalyst; In water; at 75℃; for 3h;
General procedure: A mixture of the aldehyde/ketone (0.1 mmol), compound of active methylene group (0.1 mmol), catalyst (5 mg)and solvent (toluene or water, 0.4 mL) was added in a glass tube and mechanically stirred at 75 C. The reaction progress was monitored by Gas Cromatography with FID detector. After the completion of this reaction, the catalyst was removed by magnetic separation. For there actions in toluene, the mixture was purified by using column chromatography, and for the reactions in water, the product was precipitated with cool water, filtrated and dried under low pressure. All the products were characterized by 1H NMR, and 13C NMR.
67%
General procedure: In an oven dried clean 10 ml round bottom flask equipped with a magnetic stir bar, benzaldehyde (0.9mmol) and (5f) (30mol%) were taken and stirred for 10 min. Under the stirring condition, active methylene compound (0.9 mmol) was added to the reaction mixture and allowed the reaction mixture to stir at room temperature for 30 min. Upon completion of reaction (monitored by TLC), 5 ml of ethyl acetate and water was added to the reaction mixture. Two layers formed were separated by using separating funnel. The aqueous layer was washed with ethyl acetate (5ml × 3 times). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The residue was subjected to column chromatography to obtain the corresponding product. The products were confirmed by 1H, 13C NMR and HRMS analysis.
62%
In water; at 65℃; for 4h;
In a 10 mL flask were added a solution of malonitrile (66 mg, 1 mmol) and water (1 mL). Then the cyclohexanone (104 muL, 1 mmol) was added and the reaction heated at 65C for 4 hours. The reaction mixture was cooled to room temperature and extracted with EtOAc (3 x 30 mL), the organic phase was dried over Na2SO4 and then concentrated under vacuum. 2-cyclohexylidenemalononitrile (2e): The desired product was obtained as an orange oil in 62% yield (90 mg, 0.62 mmol) without purification by column chromatography. 1H NMR (400 MHz, CDCl 3) delta: 2.70-2.60 (m, 4H), 1.85-1.75 (m, 4H), 1.74-1.64 (m, 2H). 13C NMR (100 MHz, CDCl3) delta: 185.0; 111.7; 82.6; 34.8; 28.0; 25.0; 8.6.
60%
With triethylamine; In ethanol; for 0.5h;Reflux;
A mixture of 1 mmol of cyclohexanone, 1 mmol of malonic acid dinitrile, and 0.08 mol % of triethylamine in ethyl alcohol was refluxed for 30 min. The crystals were filtered off, washed with cold ethanol, and dried in air. Yield 0.40 g (60%), mp 172-174C (mp 173.5-174.5C[6]). Found, %: C 72.99; H 6.93; N 19.79. C9H10N2. Calculated: C 73.79; H 6.85; N 19.27.
With ammonium acetate; acetic acid; In toluene; for 2h;Reflux; Dean-Stark trap;
Example 145A 2-(Cyclohexylidene)malononitrile Acetic acid was added at room temperature to a stirring mixture of malononitrile (2.65 mL, 42.1 mmol), cyclohexanone (5.03 g, 51.3 mmol) and NH4OAc (6.49 g, 84 mmol) in toluene (200 mL). The resulting mixture was heated at reflux under a Dean-Stark trap for 2 hours (6 mL water collected), then cooled to room temperature. The mixture was concentrated under vacuum, and the residue was distilled under vacuum (air bath 110-130 C./~10 mm) to provide the title compound. 1H NMR (300 MHz, CDCl3) delta ppm 1.61-1.74 (m, 2H), 1.81 (ddt, J=6.5, 6.2, 5.8 Hz, 4H), 2.66 (dd, J=6.5, 6.2 Hz, 4H).
With ammonium acetate; acetic acid; In toluene;Dean-Stark; Reflux;
General procedure: In a 100 mL round-bottomflask wasplaced with 40 mL toluene containing ammonium acetate (1000 mg) and glacialacetic acid (3 mL). Then malononitrile (30 mmol) and the ketone (33 mmol) wereadded and the reaction was refluxed and stirred vigorously, the water formed inthe reaction was removed by a Dean and Stark trap placed under the refluxcondenser. After the completion of the reaction, the mixture was cooled toambient temperature and diluted with EtOAc, then washed with brine. The organicphase was dried over Na2SO4 and the solvent wasevaporated under reduced pressure. The residue was recrystallized from ethanolcrystallization or chromatography to give pure products.
With Ni2(2,5-dihydroxybenzenedicarboxylic acid); In toluene; at -163.16℃; for 24h;
General procedure: In a typical reaction, 1mmol of each reactant was combined with 2ml of solvent, toluene for the Knoevenagel condensations or acetonitrile in the Michael addition. The mixture was added to 50mg of activated catalyst. The reaction mixture was heated to 70C, and aliquots of sample were removed for analysis at set intervals. The identity of the reaction products was verified by GC-MS (Agilent 6890 gas chromatograph, equipped with a HP-5MS column, coupled to a 5973 MSD mass spectrometer), and the product yields were determined via GC-analysis. The substrate scope was evaluated in reactions in which 1mmol of each reactant was combined with 2ml of toluene. This mixture was added to 50mg of appropriately activated Ni2dobdc and stirred at 110C.
With amino-group functionalized nanoporous polydivinylbenzene (PDVB-2.0-NH2); In ethanol; at 80℃; for 2h;
General procedure: The Knoevenagel condensation of benzaldehyde with malononitrile was performed in a flask equipped with a reflux condenser and magnetic stirrer. Typically, 2mmol of aldehydes (benzaldehyde, cyclohexanone, 4-nitrobenzaldehyde, salicylaldehyde or furfural) and 2mmol of malononitrile were dispersed into 5mL of ethanol solvent, then 0.02g of catalyst was rapidly added. After stirring of the mixture at 80C for 2h, the reaction was finished. The products were analyzed by using gas chromatography systems (Agilent 7890) with a flame ionization detector (FID). The initial temperature of the column was 100C, ramping rate was 20C/min, and the final temperature was 280C; the temperatures of the inlet and detector were 300 and 350C, respectively. In this reaction, the concentrations of products were calculated through the internal standard (dodecane) method. In the meanwhile, the catalysts could be regenerated from centrifugation, washing with large amount of ethanol, reactivated with isopropylamine and drying at 60C. The regenerated catalyst was directly used for the next run.
With Cu(2+)*NO3(1-)*C10H14O4(1-)*C10H8N2; In toluene; at 60℃; for 24h;
General procedure: Before the catalytic tests, the compound was dried at 80 C in a vacuum oven in order to removethe water molecules present in the structure, obtaining the CuHTaeBpy_HT phase. The reactionconditions were established based on the reaction between benzaldehyde and malononitrile. Once theconditions were set, the reaction was made with benzaldehyde and ethyl cyanoacetate, and withdifferent aldehydes or ketones: p-tolualdehyde, p-fluorobenzaldehyde, p-metoxybenzaldehyde,heptanal, acetophenone, cyclopentanone, and cyclohexanone. For a typical reaction, 10 mg (0.02 mmol)of catalyst were placed in a 2 mL vial with 0.5 mL of toluene anhydrous, 0.4 mmol of the substrate,10 L of dodecane as internal standard for GC-MS, and 0.6 mmol of malononitrile or ethyl cyanoacetate.Aliquots of the reaction media were taken at specific reaction times. The aliquots were analyzed byGC-MS (Agilent Technologies, Santa Clara, CA, USA) to determine the reaction progress.A hot filtration test was performed for the reaction of benzaldehyde and malononitrile. The reactorwas charged as usual and, after 2 h, the liquid was separated from the solid catalyst by filtration.The liquid was allowed to react, and aliquot samples were analyzed by GC-MS.Reusing tests were also carried out for the reaction with benzaldehyde. After each cycle, thecatalyst was recovered by centrifugation, washed with toluene three times, and dried at air conditions.Then, the reactor was charged again with the recovered catalyst and fresh reactants. This process wasrepeated four times. After all the reactions, the catalyst was recovered and analyzed by PXRD and IRspectroscopy (Jasco, Easton, MD, USA).
With tungstate-loaded triazine-based magnetic poly(bis-imidazolium ionic liquid); In water; at 20℃; for 5h;Green chemistry;
General procedure: In a round-bottomed flask, 0.5mmol alcohol, 0.75mmolH2O2, 2mL solvent water and 4mol% MNPPIL/W (26mg) were mixed and stirred at 90C for a defined time. After the completion of the reaction, monitored by TLC, the reaction was cooled down to room temperature and then 0.6mmol malononitrile was added to solution and the mixture was stirred for another 2h. Ethyl acetate was then added to the mixture and catalyst was separated by an external magnet and washed with methanol, dried at 50C and stored for another run. The product was extracted by ethyl acetate and analyzed by gas chromatography (GC).
With triethylamine; In ethanol; at 20℃; for 2h;
General procedure: Malononitrile (9.5 mmol) and the aldehyde (9.5 mmol) were dissolved in 5 mL of EtOH in a 50 mL flask, followed by adding one drop of triethylamine. After stirring at room temperature for 2 h, filtrate the solid to give the crude products. Further purification was completed by flash chromatography.
With potassium carbonate; In N,N-dimethyl-formamide; at 20℃;
General procedure: Knoevenagel adduct 1 and 2 equivalents of a propargyl bromide derivative 2 were dissolved in anhydrous DMF (0.5 M with respect to the limiting reagent). Finely ground K2CO3 (3 equivalents) was then added to the solution and stirred at room temperature until the limiting reagent was consumed (monitored by TLC; 30 min-2 hrs.). The solution was then diluted with EtOAc and washed with H2O five times. The organic layer was then washed with brine and dried with Na2SO4. The solvent was removed under reduced pressure and the crude material purified via column chromatography (hexane-ethyl acetate) unless otherwise noted. Using the foregoing method, compounds 3a-3f and 3h-3m were prepared, and are described in further detail herein below Pale yellow oil, 93% yield, 2.34 g. Purified using 10% EtOAc in hexane. 1H NMR (500 MHz, CDCl3) delta 6.30 (dq, J=3.8, 2.0 Hz, 1H), 2.97 (d, J=2.6 Hz, 2H), 2.35 (t, J=2.5 Hz, 1H), 2.23-2.11 (m, 5H), 1.79-1.72 (m, 2H), 1.63 (pd, J=6.9, 6.2, 4.1 Hz, 2H). 13C NMR (125 MHz, CDCl) delta 131.0, 127.0, 113.9, 75.2, 74.9, 43.4, 28.8, 25.4, 24.5, 22.3, 21.3. HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C12H13N2 185.1073; Found 185.1080. [M+Na]+ Calcd for C12H12N2Na 207.0893; Found 207.0883. Rf=0.51 (20% EtOAc in hexane)
General procedure for the synthesis of 2-chloro-3-cyanopyridines 4
General procedure: To a flask containing 10 mmol of a gem-dicyanoalkene 1 and 20 mmol (3.0 g) of POCl3 in DMF (10 mL), 0.1 g of phosphate catalyst (KF/NP) was added, and the mixture was stirred at room temperature for 30 min. Then the bath temperature was slowly raised to 70 - 80 °C. The reaction mixture was heated for 3 h and after cooling poured into cold water. The formed solid was filtered and recrystallized or purified by column chromatography.
11%
With trichlorophosphate 1) r.t., 30 min 2) 80-90 deg C, 4.5 h;
With triethylamine; In N,N-dimethyl-formamide; at 50℃; for 1h;
General procedure: Triethylamine, 1 mL, was added dropwise with stirring to a solution of 1.5 g (10 mmol) of cyclohexylidenemalononitrile and 10 mmol of substituted phenyl isothiocyanatein 2 mL of DMF. The mixture was stirred for 1 hat 50 C, cooled to room temperature, and diluted with 4 mL of methanol. The precipitate was filtered off, washed with water, and recrystallized from nitromethane. 3-Amino-2-phenyl-1-sulfanylidene-1,2,5,6,7,8-hexahydroisoquinoline-4-carbonitrile (1a) [12].Yield 2.252 g (78%), mp 270-271C. 1H NMR spectrum(DMSO-d6), delta, ppm: 1.75-1.81 m (4H, 6-H, 7-H),2.52-2.58 m (2H, 8-H), 2.67-2.73 m (2H, 5-H), 6.21 br.s (2H, NH2), 7.10-7.15 m (2H, Harom), 7.46-7.52 m (1H, Harom), 7.55-7.63 m (2H, Harom). 13C NMRspectrum (DMSO-d6), deltaC, ppm: 21.2, 22.4, 28.3, 28.5,78.6, 115.6, 126.5, 127.9, 128.8, 130.0, 138.7, 144.4,153.2, 181.9. Found, %: C 68.22; H 5.40; N 14.84;S 11.47. C16H15N3S. Calculated, %: C 68.30; H 5.37;N 14.93; S 11.40.
With mercapto-functionalized silica-coated nano gamma-Fe2O3-pyridine; In neat (no solvent); at 70℃; for 4h;Green chemistry;
General procedure: Catalyst 1 (5 mol%) was added to a mixture of ,-unsaturatedmalonate (5 mmol) and diethyl phosphite (10 mmol). The mixturewas stirred at 70 C for the appropriate time (Table 2). The catalystwas separated by a magnetic bar from the cooled mixture,washed with EtOH, dried 30 min at 110 C and reused for a consecutiverun under the same reaction conditions. Evaporation of thesolvent of the remaining solution under reduced pressure gave thecrude products. The pure products (2-18, Table 2) were isolated bychromatography on silica gel eluted with n-hexane:EtOAc (1:2).
3'-amino-1'-(2-fluorophenyl)-1,3-dioxo-1,3,6',7',8',8a'-hexahydro-1'H-spiro[indene-2,2'-naphthalene]-4'-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In methanol at 20℃; for 4h; Green chemistry;
4.1.1 Experimental procedure for the synthesis of (4a-m)
General procedure: Indanedione 1 (1mmol), aldehydes 2 (1mmol) 2a-h were stirred in MeOH in the presence of l-proline (20mol%) at room temperature (r.t.) for ten minutes followed by the addition of alkylidene malononitrile 3a-c (1mmol) at r.t. for 3h. The solid precipitated out, and then was filtered off and purified by recrystallization from ethanol to afford product 4a-m as yellow crystalline solid.
3'-amino-1'-(naphthalen-1-yl)-1,3-dioxo-1,3,6',7',8',8a'-hexahydro-1'H-spiro[indene-2,2'-naphthalene]-4'-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In methanol at 20℃; for 5h; Green chemistry;
4.1.1 Experimental procedure for the synthesis of (4a-m)
General procedure: Indanedione 1 (1mmol), aldehydes 2 (1mmol) 2a-h were stirred in MeOH in the presence of l-proline (20mol%) at room temperature (r.t.) for ten minutes followed by the addition of alkylidene malononitrile 3a-c (1mmol) at r.t. for 3h. The solid precipitated out, and then was filtered off and purified by recrystallization from ethanol to afford product 4a-m as yellow crystalline solid.
4.1. Experimental procedure for the synthesis of (6a-j)
General procedure: Oxindole 5 (1mmol), aldehydes 2 (1mmol) 2a-j were stirred in MeOH in the presence of l-proline (20mol%) at room temperature (r.t.) for ten minutes followed by the addition of alkylidene malononitrile 3a-c (1mmol) at r.t. for 5h. The solid precipitated out was filtered off and purified by recrystallization from ethanol to afford product 6a-j as white crystalline solid.
3'-amino-2-oxo-1'-(pyridin-2-yl)-6',7',8',8a'-tetrahydro-1'H-spiro[indoline-3,2'-naphthalene]-4'-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In methanol at 20℃; for 7h; Green chemistry;
4.1. Experimental procedure for the synthesis of (6a-j)
General procedure: Oxindole 5 (1mmol), aldehydes 2 (1mmol) 2a-j were stirred in MeOH in the presence of l-proline (20mol%) at room temperature (r.t.) for ten minutes followed by the addition of alkylidene malononitrile 3a-c (1mmol) at r.t. for 5h. The solid precipitated out was filtered off and purified by recrystallization from ethanol to afford product 6a-j as white crystalline solid.
2-amino-4-methylsulfanyl-5,6,7,8-tetrahydro-1,3-naphthalenedicarbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
General procedure: To a solution of α,α-dicyanoolefin 1 (1 mmol) and ketenedithioacetal 2 (1 mmol) in EtOH (3 mL) was added Et3N (1mmol), and the solution was stirred for 30 min at r.t. Then,excess hydrazine was added to mixture. Upon completion(2 h, monitoring by TLC), the mixture was filtered and theprecipitate washed with EtOH (2 × 4 mL) to afford the pureproducts 3a,b,e,f and 4a-d.
N-(4-bromophenyl)-3,3-dicyano-3-(cyclohex-1-en-1-yl)propanamide[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
76%
With potassium hydroxide; In water; N,N-dimethyl-formamide; at 20℃; for 2h;
General procedure: To a solution of 10 mmol of CH acid 1-3, 8, 10a, 10b, or 13-15 in 20 ml of DMF we added under stirring at 20C 5.6 mL (10 mmol) of 10% aqueous potassium hydroxide and then 10 mmol of alkylating agent 4a-4c or 5. The mixture was stirred for 2 h and diluted with an equal volume of water, and the precipitate was filtered off and washed with water, ethanol, and hexane. In the synthesis of 6a, 6b, 11, 16a, and 16b, 11.2 mL (20 mmol) of 10% aqueous potassium hydroxide and 20 mmol of phenacyl bromide 4a or 4b were used.
With triethyl borane; oxygen; In hexane; dichloromethane; at 0℃; for 0.25h;
General procedure: Et3B (1.03 M in hexane, 0.37 mL, 0.38 mmol) was added to a solution of O,Te-acetal 29a (46.1 mg, 0.128 mmol) and cyclopentenone 3a (32 mL, 0.38 mmol) in CH2Cl2 (1.3 mL) at 0 C. The reaction mixture was stirred for 15 min at 0 C, and was then directly subjected to flash column chromatography on silica gel (10 g, hexane/EtOAc 1/1) to afford 7a (26.9 mg, 0.113 mmol) in 88% yield. The analytical data of 7a were identical to those reported previously.2a
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