* 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.
General procedure: The synthesis of the title compounds (Scheme 1) follows a Knoevenangel condensation of the suitable heteroarylaldehyde (0.01 mol) with malonic acid (0.01 mol) dissolved in 1.12 mL of pyridine and piperidine (0.01 mol). The mixture was refluxed until the emission of CO2 stopped. The reaction solution was poured into 2N HCl and ice and the formed precipitate was collected by filtration and recrystallized from water or from 3:1 water/ethanol. In the case that no precipitate was formed the water phase was extracted with 3 × 100 mL CHCl3 or CH2Cl2 and the organic phase was collected, dried over Mg2SO4, and evaporated to dryness affording a residue that was recrystallized from aqueous ethanol.
Reference:
[1] Molecules, 2014, vol. 19, # 7, p. 9655 - 9674
[2] Chemistry - A European Journal, 2017, vol. 23, # 3, p. 554 - 557
[3] Organic Letters, 2017, vol. 19, # 23, p. 6412 - 6415
9
[ 104-55-2 ]
[ 105-53-3 ]
[ 1552-94-9 ]
Reference:
[1] Applied Catalysis A: General, 2010, vol. 381, # 1-2, p. 226 - 232
10
[ 104-55-2 ]
[ 1552-94-9 ]
Reference:
[1] Chemische Berichte, 1904, vol. 37, p. 2274
11
[ 104-55-2 ]
[ 927-80-0 ]
[ 1552-94-9 ]
Reference:
[1] Recueil des Travaux Chimiques des Pays-Bas, 1966, vol. 85, p. 929 - 951
12
[ 104-54-1 ]
[ 61826-40-2 ]
[ 104-55-2 ]
Reference:
[1] Applied Catalysis A: General, 2011, vol. 394, # 1-2, p. 79 - 85
13
[ 122-51-0 ]
[ 104-55-2 ]
[ 7148-78-9 ]
Reference:
[1] Synlett, 1999, # 9, p. 1456 - 1458
[2] Synlett, 1999, # 3, p. 321 - 323
[3] Journal of the Indian Chemical Society, 2008, vol. 85, # 5, p. 566 - 568
[4] Journal of Organic Chemistry, 2002, vol. 67, # 16, p. 5842 - 5845
[5] Bulletin of the Chemical Society of Japan, 2002, vol. 75, # 10, p. 2195 - 2205
[6] Synthetic Communications, 2003, vol. 33, # 12, p. 2103 - 2108
[7] Bulletin of the Academy of Sciences of the USSR, Division of Chemical Science (English Translation), 1986, vol. 35, # 4, p. 838 - 840[8] Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, 1986, # 4, p. 921 - 923
[9] Synthetic Communications, 1999, vol. 29, # 13, p. 2255 - 2263
[10] Tetrahedron Letters, 1997, vol. 38, # 45, p. 7867 - 7870
[11] Monatshefte fuer Chemie, 1927, vol. 48, p. 279
[12] Archiv der Pharmazie, 1986, vol. 319, # 12, p. 1130 - 1134
[13] Patent: US2017/275260, 2017, A1, . Location in patent: Paragraph 0554
14
[ 64-17-5 ]
[ 104-55-2 ]
[ 7148-78-9 ]
Reference:
[1] Journal of the American Chemical Society, 1925, vol. 47, p. 1365[2] Journal of the American Chemical Society, 1925, vol. 47, p. 1370
[3] Journal of the Chemical Society, 1922, vol. 121, p. 83
[4] Journal of the Chemical Society, 1922, vol. 121, p. 83
[5] Tetrahedron, 1996, vol. 52, # 26, p. 8789 - 8794
[6] New Journal of Chemistry, 2017, vol. 41, # 17, p. 9123 - 9129
15
[ 873376-62-6 ]
[ 104-55-2 ]
[ 7148-78-9 ]
Reference:
[1] Journal of the Chemical Society, Chemical Communications, 1990, # 6, p. 493 - 494
With hydroxylamine hydrochloride; p-toluenesulfonyl chloride; In 1,2-dichloro-ethane; at 90℃; for 20h;
General procedure: PTSA (0.06 mmol, 0.3 equiv) were added to a solution of propargylic alcohol (0.20 mmol, 1 equiv) in DCE (1 mL). The reaction mixture was stirred at 90 C until propargylic alcohol was completely disappeared (about 30 min). Then NH2OHHCl (0.24 mmol, 1.2 equiv) and p-TsCl (0.40 mmol, 2equiv) were added. The resulting mixture continued to be stirred at 90 C for an 20 h. Then it was cooled to room temperature, and satd aq NaHCO3 (2 mL) and CH2Cl2 (5 mL) were added. The organic layer was separated and washed successively with satd aq NaHCO3 (2×2 mL), H2O (2 mL), and brine (1 mL), then dried (MgSO4) and filtered. The filtrate was concentrated in vacuo and the resulting residue was purified by flash column chromatography [silica gel, EtOAc-PE] to give the alpha,beta-unsaturated nitrile. Compounds 3j-3o12b are known compounds.
1-(1-naphthylacetyl)-2-cinnamylidenehydrazine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75.0%
In ethanol;Reflux;
General procedure: solutionof acid hydrazide (0.01 mol) and appropriate benzaldehyde/acetophenone (0.01 mol) in ethanol was refluxed for 5-6 h. The precipitated title compounds were then filtered off, washed with water and recrystallized from ethanol.
[0147] (S)-3-(4-Dimethylamino-2-methoxy-phenyl)-3-phenyl-propanol: To a 50-mL roundbottom flask equipped with a magnetic stir bar was added (2S,5S)-5-benzyl-2-tert-butyl-3-methylimidazolidin-4-one (0.394 g, 1.60 mmol, 0.100 equiv), CH2Cl2 (16.0 mL), HCl (as a 4N solution in 1,4-dioxane, 0.400 mL, 1.60 mmol, 0.100 equiv), and N,N-dimethyl-m-anisidine (4.69 mL, 32.0 mmol, 2.00 equiv). The reaction vessel was cooled to 0o C. before the addition of cinnamaldehyde (2.06 ml, 16.0 mmol, 1.00 equiv). The solution was stirred for 12 h at 0o C. and then warmed to ambient temperature and stirred for an additional 6 h. At that time, the reaction mixture was added drop-wise to a stirring suspension of NaBH4 (0.750 g, 0.198 mmol, 1.24 equiv) in ethanol. After 5 min, the reduction was quenched with saturated aqueous NaHCO3 solution and diluted with CH2Cl2. The layers were separated and the organic was washed with saturated aqueous NaHCO3 and brine solutions. The resulting solution was dried over sodium sulfate and concentrated in vacuo to give a pale yellow residue, which was purified by silica gel chromatography. Gradient elution with 25-50% EtOAc in hexanes afforded the product as a colorless oil in 81% yield (3.70 g, 13.0 mmol); 74% ee. 1H NMR (300 MHz, CDCl3) ?7.32-7.12 (m, 5H, ArH), 6.99 (d, J=8.2 Hz, 1H, ArH), 6.31 (dd, J=2.7, 8.8 Hz, 1H, ArH), 6.27 (d, J=2.2, Hz, 1H, ArH), 4.51 (dd, J=6.6, 8.8 Hz, 1H, ArCH), 3.83 (s, 3H, OCH3), 3.65-3.48 (m, 2H, CH2OH), 2.93 (s, 6H, N(CH3)2), 2.38-2.12 (m, 2H, CHCH2), 1.98 (br s, 1H, OH); 13C NMR (75 MHz, CDCl3) ?157.8, 150.5, 145.5, 128.8, 128.4, 128.2, 125.9, 121.3, 105.5, 96.6, 61.6, 55.9, 41.1, 38.7, 38.2. [0148] The enantiomeric ratio of the product was determined by HPLC analysis using a Chiracel AD and AD guard column (10% ethanol/hexanes, 1 mL/min); R isomer tr=12.9 min, S isomer tr=18.1 min.
methyl (1S,2R,3S,10bS)-1-[(1E)-3-ethoxy-3-oxoprop-1-en-1-yl]-8,9-dimethoxy-3-methyl-2-phenyl-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline-3-carboxylate[ No CAS ]
methyl 1-[(1E)-3-ethoxy-3-oxoprop-1-en-1-yl]-8,9-dimethoxy-3-methyl-2-phenyl-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinoline-3-carboxylate[ No CAS ]
3-(4-methyl-2-oxo-1,2-dihydroquinolin-7-yl)-2-styrylthiazolidin-4-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
74%
General procedure: A mixture of appropriate heterocyclic amine (1.0 mmol) (3) and aromatic aldehyde (1.2 mmol) (4) were stirred in tetrahydrofuran under ice-cold condition for 5 min, followed by addition of the thioglycolic acid (2.0 mmol). After 5 min, dicyclohexylcarbodiimide(1.2 mmol) was added to the reaction mixture at 0 C and the reaction mixture was stirred for an additional 3-5 h at room temperature to complete the reaction. Progresses of the reactions were monitored by TLC using acetone:chloroform (7:3) as mobile phase. The precipitated dicyclohexylurea was filtered off; the filtrate was concentrated to drynessunder reduced pressure. Deionized water was added to the residueand extracted with ethylacetate. The organic layer was successively washed with 5% aqueous sodium hydrogen carbonate and sodium chloride. Finally organic layer was dried over anhydrous sodium sulfate. The crude solid obtained on evaporation of the solvent under reduced pressure was subjected for column chromatography using silica gel 100-200 mesh using n-hexane:ethyl acetate (7:3) as the solvent system and further recrystallized in acetone to yield white/yellowish-white products[42].
General procedure: Toa solution of catalyst 3c (0.02 mmol) andPNAB (0.02 mmol) in CHCl3 (0.5mL) was added alpha,beta-unsaturated aldehydes 2 (0.22 mmol) at roomtemperature. After being stirred for 10 minute, 3(2H)-furanones 1 and CHCl3 (0.5 mL)were added, and the resulting mixture was stirred for 3-5 d at 30 oC. Thereaction mixture wasconcentratedand flushed through a short plug of silica (PE-EtOAc, 5:1-3:1)to afford 4. Then,4 was dissolved in MeOH (2 mL), and NaBH4 (14 mg) was cautiously added.After being stirredat 0 oC for 0.5 h, the reaction systemwas quenched withwater (1 mL) and HCl (1M).The organic phase was separated and the aqueous solution was extracted withethyl acetate (1 mL x 3). The combined organic phases were washed with brineand dried over anhydrous Na2SO4. The solvent was removedunder reduced pressure and the residue was purified by silica gel column chromatography (PE-EtOAc, 3:1-1:1) to afford thedesired product 5. All products were confirmed by 1H NMR, 13C NMR and HRMS spectroscopic analysis. The diastereomeric ratio wasdetermined by crude NMR analysis and the enantiomeric excess was determined bychiral-phase HPLC analysis.
General procedure: Toa solution of catalyst 3c (0.02 mmol) andPNAB (0.02 mmol) in CHCl3 (0.5mL) was added alpha,beta-unsaturated aldehydes 2 (0.22 mmol) at roomtemperature. After being stirred for 10 minute, 3(2H)-furanones 1 and CHCl3 (0.5 mL)were added, and the resulting mixture was stirred for 3-5 d at 30 oC. Thereaction mixture wasconcentratedand flushed through a short plug of silica (PE-EtOAc, 5:1-3:1)to afford 4. Then,4 was dissolved in MeOH (2 mL), and NaBH4 (14 mg) was cautiously added.After being stirredat 0 oC for 0.5 h, the reaction systemwas quenched withwater (1 mL) and HCl (1M).The organic phase was separated and the aqueous solution was extracted withethyl acetate (1 mL x 3). The combined organic phases were washed with brineand dried over anhydrous Na2SO4. The solvent was removedunder reduced pressure and the residue was purified by silica gel column chromatography (PE-EtOAc, 3:1-1:1) to afford thedesired product 5. All products were confirmed by 1H NMR, 13C NMR and HRMS spectroscopic analysis. The diastereomeric ratio wasdetermined by crude NMR analysis and the enantiomeric excess was determined bychiral-phase HPLC analysis.
(4S)-6-(4-fluorophenyl)-2-hydroxy-4-phenyl-3,4-dihydro-2H-pyran-5-carbonitrile[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
87%
With (S)-2-{bis(3,5-dimethylphenyl)[(trimethylsilanyl)oxy]methyl}pyrrolidine; 3,5-dinitrobenzoic acid; In toluene; at 0℃; for 48h;
General procedure: To a solution of catalyst 4 (0.01mmol), 3,5-(NO2)2C6H3CO2H (0.02mmol), and alpha,beta-unsaturated aldehyde 2 (0.10mmol) in toluene (1.0mL) was added alpha-cyanoketones 1 (0.15mmol) at 0C. The resulting solution was then stirred for 48h. After complete consumption of the aldehyde (as monitored by TLC), the reaction mixture was evaporated and then loaded onto silica gel (ethyl acetate/petroleumether=1:10 to 1:7) and the products 3a-n were obtained by column chromatography. The title compound was obtained according to the general procedure (87% yield) as a mixture of two diastereoisomers (major and minor). Yellow solid; [alpha]D30=+8.1 (c 1.05, MeOH); mp=168-170C; 1H NMR (400MHz, DMSO-d6): delta 7.81-7.77 (m, 3H; both diastereoisomers), 7.40-7.30 (m, 7H; both diastereoisomers), 5.62 (s, 1H; both diastereoisomers), 4.01 (dd, J=10.8, 6.0Hz, 1H; minor), 3.91 (dd, J=9.6, 6.0Hz, 1H; major), 2.35-2.30 (m, 1H; minor), 2.18-2.12 (m, 1H; major), 1.97-1.90 (m, 1H; major), 1.88-1.80 (m, 1H; minor); 13C NMR (100MHz, DMSO-d6): delta 163.6 (JCF=247.5Hz), 162.8, 142.4, 131.0 (JCF=8.4Hz), 130.5, 129.2, 128.4, 128.1, 127.6, 119.9, 115.9 (JCF=22.0Hz), 97.3, 93.2, 87.5, 36.6, 36.1ppm; (additional peaks are observed due to diastereoisomers). IR (KBr): nu 3363.4, 2206.8, 1602.7, 1507.3, 1455.3, 1238.0, 1139.8, 1091.5, 838.4, 766.8cm-1; d.r.: trans/cis=2.58/1; ESI-MS (m/z): 318.1 (M+Na)+; HRMS(ESI): calcd for ([C18H14FNO2Na+]): 318.0901. Found: 318.0902; enantiomeric excess: 97%, determined by HPLC (Chiralcel OD-H column, hexane/ i-PrOH 80:20, flow rate 0.7mL/min; lambda=254nm, tmajor=16.9min, tminor=10.8min).
With oxygen; potassium hydroxide; In dimethyl sulfoxide; at 120℃; under 760.051 Torr; for 12h;Green chemistry;
General procedure: A mixture of benzamidine hydrochloride 1a (0.25mmol), cinnamaldehyde 2a (0.30mol) and KOH (0.50mmol, 2equiv.) was stirred in DMSO (1.0mL) under 1atm O2 atmosphere at 120°C for 12h. After completion of the reaction (monitored by TLC), water (10mL) was added to the reaction mixture, and the resulting mixture was extracted with ethyl acetate. The combined organic layers were then dried over MgSO4, filtered, and then concentrated in vacuo. The residue was purified by flash chromatography on silica gel to give the desired product 3aa as a white solid (using the mixture of petroleum ether and ethyl acetate as eluents).
With oxygen; potassium hydroxide; In dimethyl sulfoxide; at 120℃; under 760.051 Torr; for 12h;Green chemistry;
General procedure: A mixture of benzamidine hydrochloride 1a (0.25mmol), cinnamaldehyde 2a (0.30mol) and KOH (0.50mmol, 2equiv.) was stirred in DMSO (1.0mL) under 1atm O2 atmosphere at 120C for 12h. After completion of the reaction (monitored by TLC), water (10mL) was added to the reaction mixture, and the resulting mixture was extracted with ethyl acetate. The combined organic layers were then dried over MgSO4, filtered, and then concentrated in vacuo. The residue was purified by flash chromatography on silica gel to give the desired product 3aa as a white solid (using the mixture of petroleum ether and ethyl acetate as eluents).
With oxygen; potassium hydroxide; In dimethyl sulfoxide; at 120℃; under 760.051 Torr; for 12h;Green chemistry;
General procedure: A mixture of benzamidine hydrochloride 1a (0.25mmol), cinnamaldehyde 2a (0.30mol) and KOH (0.50mmol, 2equiv.) was stirred in DMSO (1.0mL) under 1atm O2 atmosphere at 120°C for 12h. After completion of the reaction (monitored by TLC), water (10mL) was added to the reaction mixture, and the resulting mixture was extracted with ethyl acetate. The combined organic layers were then dried over MgSO4, filtered, and then concentrated in vacuo. The residue was purified by flash chromatography on silica gel to give the desired product 3aa as a white solid (using the mixture of petroleum ether and ethyl acetate as eluents).
With oxygen; potassium hydroxide; In dimethyl sulfoxide; at 120℃; under 760.051 Torr; for 12h;Green chemistry;
General procedure: A mixture of benzamidine hydrochloride 1a (0.25mmol), cinnamaldehyde 2a (0.30mol) and KOH (0.50mmol, 2equiv.) was stirred in DMSO (1.0mL) under 1atm O2 atmosphere at 120°C for 12h. After completion of the reaction (monitored by TLC), water (10mL) was added to the reaction mixture, and the resulting mixture was extracted with ethyl acetate. The combined organic layers were then dried over MgSO4, filtered, and then concentrated in vacuo. The residue was purified by flash chromatography on silica gel to give the desired product 3aa as a white solid (using the mixture of petroleum ether and ethyl acetate as eluents).
General procedure: The mixture of <strong>[78364-55-3]6-fluoro-2-hydrazinylbenzo[d]thiazole</strong> (2) (0.01 mol) and benzalde-hyde/substituted benzaldehyde (0.01 mol) was reuxed in ethanol (15 ml) at 70?80 °C for 3 h. The separated product obtained was ltered off, washed withdistilled water and recrystallized from methanol to give the correspondinghydrazone. The product obtained was further dissolved in acetic acid (20 ml) atroom temperature followed by the addition of sodium acetate (0.5 g). Bromine(2 mmol) in acetic acid (10 ml) was added dropwise to the reuxing reactionmixture. After 1 h, the mixture was poured onto crushed ice (100 g). The precipitateobtained was ltered off and crystallized from ethanol-dimethylformamide (1:1) togive crystals of (3a?3t).
7-methyl-2-phenethylquinazolin-4(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
80%
With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; In toluene; at 120℃; for 12h;Inert atmosphere;
Under nitrogen atmosphere, <strong>[39549-79-6]2-amino-4-methylbenzamide</strong> (150 mg, 1 mmol), [Cp*IrCl2]2 (8 mg, 0.01 mmol, 1 molpercent), toluene (1.0 mL), cinnamaldehyde (132 mg, 1 mmol)Add to a 25 mL Schlenk reaction flask.The mixture was reacted at 120°C for 12 hours and then cooled to room temperature.The solvent was removed in vacuo under reduced pressure and then purified by column chromatography (developer: ethyl acetate/petroleum ether) to give the pure target compound, yield: 80percent.
6-methoxy-2-phenethylquinazolin-4(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
77%
With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; In toluene; at 120℃; for 12h;Inert atmosphere;
Under nitrogen atmosphere, <strong>[1882-71-9]2-amino-5-methoxybenzamide</strong> (166 mg, 1 mmol), [Cp*IrCl2]2 (8 mg, 0.01 mmol, 1 molpercent), toluene (5.0 mL), cinnamaldehyde (132 mg, 1 mmol) was added sequentially to a 25 mL Schlenk reaction flask. The mixture was reacted at 120°C for 12 hours and then cooled to room temperature. The solvent was removed in vacuo under reduced pressure and then purified by column chromatography (developer: ethyl acetate/petroleum ether) to give the pure target compound in a yield of 77percent.
7-chloro-2-phenylethylquinazolin-4(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
86%
With bis[dichloro(pentamethylcyclopentadienyl)iridium(III)]; In toluene; at 120℃; for 12h;Inert atmosphere;
Under nitrogen protection, <strong>[5900-59-4]2-amino-4-chlorobenzamide</strong> (171 mg, 1 mmol), [Cp*IrCl2]2 (8 mg, 0.01 mmol, 1 molpercent), toluene (1.0 mL), cinnamaldehyde (132 mg, 1 mmol)Add 25mL Schlenk reaction flasks one by one.The mixture was reacted at 120°C for 12 hours and then cooled to room temperature.The solvent was removed in vacuo under reduced pressure and then purified by column chromatography (developer: ethyl acetate/petroleum ether) to give the pure target compound in a yield of 86
2-methyl-3-((3-phenylallylidene)amino)benzoic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In methanol; at 60℃; for 3h;
General procedure: The general condensation reaction to form Schiff base underwentaddition-elimination procedure. To a vial, 1 equiv. (1 mmol)of aromatic aldehyde (A moiety) and 1 equiv. of aromatic primaryamine (B moiety) were added and dissolved in 6 mL of absolutemethanol. After heating and stirring at 60 C for 3 h (or longerbased on TLC), the mixture was set for 48-72 h to generate thesolid Schiff base. Collecting the crystal from the solvent andchecked with TLC, if aromatic aldehyde or aromatic primary amine presented, removing them by column chromatography with 1:4ethyl acetate: petroleum ether to obtain pure product (80-90%).
(E)-5,5-dimethyl-2-(2-styryl-1H-imidazol-5-yl)-2,5-dihydrothiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
76%
With silica-gel-supported sulfuric acid; ammonium acetate; In neat (no solvent); at 130℃; for 2h;
General procedure: To a mixture of aldehyde (1 mmol), <strong>[551-16-6]6-aminopenicillinic acid</strong> (1 mmol), and ammonium acetate (3 mmol), SiO2*H2SO4 (0.025 g) was added and heated in an oil bath up to 130 C in appropriate times. After the completion of the reaction (TLC monitoring, EtOAc: hexane 10/90 v/v), the mixture was diluted in hot ethanol, solid was filtered, and products were purified by recrystallization in watery ethanol.