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Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
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Structure of 104-88-1 * Storage: {[proInfo.prStorage]}
* 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] Journal of the American Chemical Society, 2001, vol. 123, # 31, p. 7705 - 7706
2
[ 104-88-1 ]
[ 62882-02-4 ]
Reference：
[1] Gazzetta Chimica Italiana, 1959, vol. 89, p. 2222,2226
3
[ 104-88-1 ]
[ 16687-61-9 ]
Yield
Reaction Conditions
Operation in experiment
66%
With sodium azide; cerium(IV) tetraammonium sulfate dihydrate; hydroxylamine hydrochloride In N,N-dimethyl-formamide for 6 h; Reflux; Green chemistry
General procedure: Aldehyde (1 mmol), hydroxylamine hydrochloride (2 mmol) and sodium azide (2 mmol) were added successively to a solution of (NH4)4Ce(SO4)4·2H2O (20 molpercent) in 5 mL DMF. The mixture was reflux for appropriate time (Table 2). The progress of the reaction was monitored by TLC. After completion of the reaction, the solution was treated with HCl (4N, 10 mL) and then the solution was poured into 100 mL water and extract with ethyl acetate, washed several times with water. The combined organic mixture was dried over anhydrous Na2SO4, concentrated and the residue was purified by column chromatography on silica gel 60-120 mesh using petroleum ether/ethyl acetate (75:25) as eluent to afford the pure solid tetrazole. All the products were characterized by 1H NMR, 13C NMR and HRMS.
Reference：
[1] RSC Advances, 2016, vol. 6, # 94, p. 91999 - 92006
[2] New Journal of Chemistry, 2015, vol. 39, # 3, p. 2116 - 2122
[3] Applied Organometallic Chemistry, 2018, vol. 32, # 4,
[4] Synlett, 2012, vol. 23, # 20, p. 2927 - 2930
[5] Synthesis (Germany), 2013, vol. 45, # 4, p. 507 - 510
[6] Tetrahedron Letters, 2018, vol. 59, # 14, p. 1385 - 1389
[7] Synthetic Communications, 2011, vol. 41, # 14, p. 2081 - 2085
[8] Tetrahedron Letters, 2016, vol. 57, # 5, p. 523 - 524
[9] Journal of Chemical Research, 2017, vol. 41, # 1, p. 25 - 29
[10] Synthetic Communications, 2017, vol. 47, # 7, p. 695 - 703
4
[ 109-04-6 ]
[ 104-88-1 ]
[ 27652-89-7 ]
Reference：
[1] Organic and Biomolecular Chemistry, 2015, vol. 13, # 43, p. 10681 - 10690
5
[ 110-86-1 ]
[ 104-88-1 ]
[ 27652-89-7 ]
Reference：
[1] Chemical Communications, 2013, vol. 49, # 21, p. 2124 - 2126
6
[ 98-98-6 ]
[ 104-88-1 ]
[ 27652-89-7 ]
Reference：
[1] Chemistry - A European Journal, 2014, vol. 20, # 14, p. 4156 - 4162
[2] Journal of the American Chemical Society, 1949, vol. 71, p. 887,889
Reference：
[1] Journal of Medicinal Chemistry, 1991, vol. 34, # 4, p. 1283 - 1292
[2] Bioorganic and Medicinal Chemistry Letters, 2013, vol. 23, # 6, p. 1760 - 1762
[3] Organic Letters, 2016, vol. 18, # 15, p. 3586 - 3589
9
[ 87-41-2 ]
[ 104-88-1 ]
[ 53242-88-9 ]
Yield
Reaction Conditions
Operation in experiment
24.8%
Stage #1: With sodium hydroxide In methanol; ethyl acetate at 80℃; Stage #2: at 80℃;
Isobenzofuran-l(3H)-one (0.50 g, 1.0 eq.) was dissolved in methanol (2.0 mL) and ethyl acetate (10.0 mL) and then 4-chlorobenzaldehyde (0.52 g, 1.0 eq.) was added thereto. NaOH (0.60 g, 4.0 eq.) was dissolved in methanol (8.0 mL) and added to the reaction solution. The mixture was then stirred overnight at 80°C. After confirming the disappearance of the starting material by TLC, the reaction solution was concentrated under reduced pressure. Water and ethyl acetate were added to the obtained residue, and the extracted organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Hydrazine hydrate (20.0 mL) was added to the obtained residue, followed by stirring overnight at 80°C. The reaction solution was cooled at room temperature and concentrated under reduced pressure. Ethanol (10.0 mL) was added to the obtained residue and cooled to 0°C using ice. After confirming that a transparent red solid was crystallized, it was filtered to obtain the desired intermediate 4- (4-chlorobenzyl)phthalazin-l(2H)-one (0.25 g, yield 24.8percent).
Reference：
[1] Journal of Medicinal Chemistry, 2012, vol. 55, # 17, p. 7525 - 7545
[2] New Journal of Chemistry, 2016, vol. 40, # 10, p. 8846 - 8854
18
[ 104-88-1 ]
[ 26385-24-0 ]
[ 3446-89-7 ]
Reference：
[1] Patent: US2761873, 1953, ,
[2] Journal of medicinal chemistry, 1971, vol. 14, # 11, p. 1113 - 1115
19
[ 2446-51-7 ]
[ 104-88-1 ]
[ 85-56-3 ]
Reference：
[1] Chemical Communications, 2013, vol. 49, # 82, p. 9464 - 9466
20
[ 141-97-9 ]
[ 104-88-1 ]
[ 57-13-6 ]
[ 5948-71-0 ]
Yield
Reaction Conditions
Operation in experiment
100%
With copper(II) bis(trifluoromethanesulfonate) In ethanol at 100℃; for 1 h; Microwave irradiation; Inert atmosphere
General procedure: Aldehyde (1.0 mmol), ethyl acetoacetate (1.0 mmol), urea (1.5 mmol), Cu(OTf)2 (0.02 mmol), and EtOH (2 mL) were added to a microwave vial equipped with a magnetic stir bar. The reaction vessel was sealed and irradiated in a microwave reactor (CEM Discover.(TM). system) at a temperature of 100 °C for 1 h at a maximum power of 200 W. The reaction mixture was cooled to room temperature overnight and the resulting precipitate was filtered and washed with H2O and hexane. The identity and purity of the products were confirmed by TLC, high-resolution mass spectrometry, IR and 1H and 13C NMR spectroscopy
98%
With bismuth vanadate In neat (no solvent) at 120℃; for 0.166667 h; Green chemistry
General procedure: A mixture of the aldehyde, oxime and/or acylal (1 mmol),1,3-dicarbonyl compound (1 mmol), urea (or thiourea)(1.2 mmol) and BiVO4-NPs (30 mg, 9.3 molpercent) was heatedin an oil bath (120 °C) under solvent-free conditions. Aftercompletion of the reaction (monitored by TLC), the reactionmixture was cooled to room temperature and EtOH(5 mL) was added and filtered to separate the catalyst. Thenthe crude product was recrystallized from EtOH to give thepure product
97%
With N-sulfonic acid poly(4-vinylpyridinium) chloride In neat (no solvent) at 100℃; for 0.0833333 h;
General procedure: A mixture of the aldehyde (1 mmol), 1,3-dicarbonyl compound (1 mmol), urea (or thiourea) (1.2 mmol) and NSPVPC (20 mg) was heated in an oil-bath (100 °C) under solvent-free conditions. After completion of the reaction (monitored by TLC) the reaction mixture was cooled to room temperature, EtOH (5 mL) was added and filtered to separate the catalyst. Then the crude product was recrystallized from EtOH to give the pure product.
97%
With Graphite In neat (no solvent) at 70℃; for 2 h; Green chemistry
General procedure: A mixture of benzaldehyde (106mg, 1mmol), urea (60mg, 1mmol), ethylacetoacetate (130mg, 1mmol) and (10mg, 10percentw/w) graphite was heated at 70°C (120°C in case of thiourea). The heterogenous mixture slowly became clear and a solid product started to seperate out. After completion of the reaction (1h, TLC) the entire mass solidified. The solid mass was crushed, washed with 5mL of cold water to remove unreacted urea and filtered.The solid was then dissolved in hot ethanol, and the catalyst was separated by filtration. On cooling the filtrate pure crystals of the product (1a) was obtained, yield 97percent (237mg). In all the cases, the product obtained was characterized by comparing spectral data and melting points with literature data.
97%
at 60℃; for 0.666667 h;
General procedure: First, 2 mmol of aldehyde, 2mmol of ethyl acetoacetate, and 2 mmol of urea were stirred for 5 min at 60 C, and then the catalyst (0.1 g) was added, and stirring was continued at 60 C using a magnetic stirrer (Scheme 6) for an appropriate time (Table 4). After completion of the reaction (monitored by TLC), the product was extracted with ethyl acetate and filtered off using a vacuum pump. The product was obtained after removal of the solvent under reduced pressure and finally crystallized from ethanol.
97.59%
With [Co(2,5-di(pyridin-4-yl)-1,3,4-oxadiazole)2(H2O)4](4-methylbenzenesulphonate)2(H2O)2 In neat (no solvent) at 80℃; for 2 h; Green chemistry
General procedure: In the presence of a catalytic amount of MCCs (0.02mmol), a mixture of aldehyde (1mmol), ethyl acetoacetate (2mmol) and urea (1.5mmol) under solvent-free condition was heated 80°C in an oil bath for 2h. After the completion of the reaction, the reaction mixture was filtered and washed with cold water and methanol to afford the pure target product.
97%
With 1,4-diazaniumbicyclo[2.2.2]octane diacetate In neat (no solvent) at 80℃; for 0.133333 h; Green chemistry
General procedure: A mixture of aldehyde (1 mmol: 0.10 mL of aldehyde 1a, 0.14 g of aldehyde 1b, 0.12 g of aldehyde 1c, 0.13 g of aldehyde 1d, 0.15 g of aldehyde 1e, 0.15 g of aldehyde 1f, 0.17 g of aldehyde 1g, 0.12 g of aldehyde 1h, 0.18 g of aldehyde 1i, 0.15 g of aldehyde 1j, 0.12 g of aldehyde 1k, 0.08 mL of aldehyde 1l, 0.09 mL of aldehyde 1m, 0.07 mL of aldehyde 1n), ethyl acetoacetate (1 mmol), urea (1 mmol) or thiourea (1 mmol) and [DABCO] dihydroacetate (0.5 mmol) washeated at 80 °C for the required reaction time according to Table 1. After the completion of the reaction, as indicated by TLC, the reaction mixture was resolved in 20 mL of H2O. The product was separated by filtration and recrystallized from EtOH and dried to afford powdery compounds of 4a-q. The filtrate was concentrated under reduced pressure and washed with diethyl ether. Then, it was dried in a vacuum evaporator to recover the ionic liquid for subsequent use.
97%
With yttrium(lll) nitrate hexahydrate In ethanol at 70℃; for 0.333333 h; Microwave irradiation
General procedure: A mixture of ethylacetoacetate (1.54 mmol), aromatic or aliphatic aldehyde (1.54mmol), urea (1.84 mmol) and Y(NO3)3·6H2O (30.7 µmol) in 10mL Ethanol in a 100 mL round bottom flask fitted condenser was subjected to microwave heating at 70 °C for appropriatetime as mentioned in the Table-1. Then the reaction mixture was allowed to cool at room temperature and H2O (20 mL) was added.The precipitate appeared was collected by filtration and washedwith water. The solid obtained was further washed with n-Hexaneto remove excess aldehyde to get analytically pure product.
96%
at 60℃; for 0.0333333 h; Microwave irradiation
General procedure: A mixture of aldehyde (1.0 mmol), ethyl acetoacetate(1.0 mmol), urea (1.5 mmol), and nano-g-Fe2O3eSO3H was placedin a microwave reaction vial. The LG microwave oven MG 555f wasprogrammed to 250 W at 60 C. The progress of the reaction wasmonitored by TLC. After completion of the reaction, ethyl acetate(5 mL) was added and the catalyst was separated by applying anexternal magnet. The solvent was evaporated and the residue was recrystallized from EtOH/H2O to give a pure product, which gavesatisfactory spectroscopic data (1H NMR, 13C NMR, and IR) andmelting point, compared to data with those of samples synthesizedby reported procedures.
96%
With N,N-diethyl-N-sulfoethanamminium hydrogen sulfate In neat (no solvent) at 70℃; for 0.25 h; Green chemistry
General procedure: To a mixture of compounds consisting of arylaldehyde (1 mmol),β-ketoester (1 mmol) and urea (0.072 g, 1.2 mmol) or thiourea(0.091 g, 1.2 mmol) in a test tube, was added [Et3N–SO3H]HSO4(0.014 g, 0.05mmol). The resulting mixture was firstly stirred magneticallyat 70 °C, and after solidification of the reaction mixture, it wasstirred by a small rod at same temperature. After completion of thereaction, as monitored by TLC, the reaction mixture was cooled toroom temperature, and the resulting precipitate was recrystallizedfrom EtOH (95percent) to give the pure product.
96%
With Fe+3-montmorillonite K10 In neat (no solvent) for 0.166667 h; Milling; Green chemistry
General procedure: A mixture of aldehyde (1mmol), ethyl acetoacetate (1mmol), urea (1mmol) or thiourea (1mmol) and Fe+3-montmorillonite K10 (0.1 g) were added to a mortar and the mixture was pulverized with a pestle. A spontaneous reaction took place (Table 2, monitored every 20seconds by TLC EtOAc : petroleum ether 1:4 drops. After completion of reaction, as indicated by TLC, the reaction product was extracted by CHCl3/H2O. After evaporation of organicsolvent, the crude product was released and recrystallized from EtOH and dried to affordpowdery compounds of 4a-s. All of synthesized compound are known and were characterizedby IR, NMR and elemental analysis.
96%
With sodium tosylate In water at 20℃; for 1.4 h; Green chemistry
General procedure: A one-pot condensation of ethyl acetoacetate (1 mmol), aldehyde (1 mmol), and urea (1 mmol) was carried out by using a hydrotropic solution of NaPTS in a100 mL round-bottom flask containing 10 mL distilled water under normal temperature and pressure conditions. Ni-ZnO nanoparticles or ZnO nanoflakes (1 molpercent) were, respectively, used as a catalyst. The reaction mixture was stirred by using a magnetic stirrer under normal temperature and pressure conditions. The reaction was monitored by using the TLC technique (ethyl acetate:hexane 2:8, v/v). Ethyl acetate (15 mL) was added to the reaction mixture after completion of the reaction. Finally, the reaction mixture was centrifuged at 4000 rpm for 10 min. The catalyst settled at the bottom of the reaction mixture and the product was taken out of the pot. The catalyst was washed with deionized water and ethyl acetate and then dried in an oven at 120 °C before recycling. The procedure for the synthesis of DHPMs isshown in Fig. 1.
95%
With gallium(III) triflate In neat (no solvent) at 90℃; for 0.5 h; Green chemistry
General procedure: To a mixture of alkyl acetoacetate (or cycloketone) (1.0 mmol), aldehyde (1.0 mmol, for cycloketones: 2.0 mmol) and urea (or thiourea) (1.2 mmol), 0.1 equivalent Ga(OTf)3 was added. The mixture was stirred at 90 oC for appropriate time. After reaction completed by TLC analysis, water was added and the product was extracted with EtOAc. The organic layer was dried over anhydrous Na2SO4 and evaporated. The residue was recrystallized from methanol or ethanol to obtain pure products.
95%
With 1,3-disulfonic acid benzimidazolium chloride In neat (no solvent) at 80℃; for 0.116667 h;
General procedure: In a 10-mL round-bottom flask equipped with a condenser, a mixture of the aromatic aldehyde (1 mmol), ethyl acetoacetate (1 mmol), urea or thiourea (1.5 mmol) and [Dsbim]Cl (0.0376 g, 10 molpercent) was stirred at 80°C, and the resulting mixture was kept under continuous stirring for lengths of time as specified in Table 3, with the progress of the reaction was followed by TLC. After completion of the reaction, the mixture was cooled to room temperature, and 3 mL of water was added. The ionicliquid was dissolved in water and filtered for separation of the crude product. The separated product was washed twice with water (2 9 3 mL). For recycling the catalysts, after the solid products were thoroughly washed with water, the water containing the ionic liquid (IL is soluble in water) was evaporated under reduced pressure, and the ionic liquid was recovered and reused. The solid product was purified by a recrystallization procedure in ethanol. All of the desired product(s) were characterized by comparison of their physical data with those of known compounds.
95%
With Punica granatum peel In neat (no solvent) at 100℃; for 0.0833333 h; Green chemistry
General procedure: To a mixture of benzaldehyde (1 mmol, 0.106 g), ethyl acetoacetate (1 mmol,0.130 g) and Punica granatum peel (0.03 g) at 100 °C, urea (1 mmol, 0.060 g) was added with stirring. The progress of the reaction was monitored by thin layer chromatography (TLC). After completion of the reaction, the reaction mixture was cooled to room temperature. Then, cold distilled water (5 mL) was poured into the reaction flask, and the resultant mixture was decanted. The brown precipitate was dissolved in hot EtOH (3 mL) and the catalyst was separated by filtration. Then, the filtrate was distilled under reduced pressure and finally the crude product was recrystallized by EtOH to give the pure product (0.247 g, 95percent).
95%
With silicon-supported ionic liquid catalyst In ethanol at 20 - 30℃; for 0.5 h;
In a 25 mL round bottom flask, 4-chlorobenzaldehyde (0.140 g, 1 mmol) was added,Acetoacetate (0.130 g, 1 mmol), urea (0.060 g, 1 mmol),Catalyst (Si-IL) (0.0121 g, 10 molpercent) and 4 mL of absolute ethanol at room temperature,The reaction was carried out for 30 minutes under normal pressure, filtered and the ethanol was washed and the catalyst was recovered. The crude product obtained by removing the ethanol from the filtrate was recrystallized from 90percent ethanol (ethanol, volume ratio 9: 1) to obtain a pure product, Yield 95percent.
94%
With bismuth (III) nitrate pentahydrate; silica gel In neat (no solvent) at 150℃; for 0.025 h;
General procedure: A mixture of aldehyde (1 mmol), ethyl acetoacetate (1.1 mmol), urea or thiourea (1.1 mmol), was added to a round bottom flaskcontaining a mixture of silica gel (0.25 g) and catalyst (5 mole percent). The mixture was heated at 150 °C in oil bath for an appropriate duration of time (1-3 min). The completion of the reaction was confirmed by TLC. The same silica gel was loaded on a silica gel column and chromatographic separation using hexane-ethyl acetate furnished the products (4a-p).
94%
With sulphated silica tungstic acid In neat (no solvent) at 70℃; for 0.166667 h; Green chemistry
Aldehyde (3 mmol), ethyl acetoacetate or acetyl acetone (3.5 mmol), urea (4.5 mmol) and SSTA (200 mg) were mixed in a 25 mL round bottom flask for specified time (Table 4) at a temperature of 70 °C. The reaction mixture was cooled and added ethanol to solubilize the product. Catalyst was recovered by above-mentioned procedure. The filtrate was evaporated under reduced pressure to obtain the product. The compounds were recrystallized from ethanol.
94%
With polyethylene supported Fe immobilization of alkyl imidazolium ionic liquid groups In neat (no solvent) at 80℃; for 1.83333 h;
General procedure: For this, the PEt(at)Fe/IL catalyst (0.75 molpercent) was added to a homogeneous mixture of aldehyde (2 mmol), ethylacetoacetate (2 mmol) and urea (3 mmol). This was then magnetically stirred at 80 C while the reaction progress was monitored by thin layer chromatography (TLC). After completion of the process, hot ethanol (10 mL) was added to the reaction flask and the obtained solution was hotly filtered. The filtrate was then placed in an ice bath to precipitate crude crystals. These were recrystallized in ethanol to give pure Biginelli products in high to excellent yields. The products were characterized by IR, 1H-NMR, 13C-NMR and via comparison of their melting points with the reported ones.
94%
With 20percent loaded [Dsim][CF3COO]/NaY composite In neat (no solvent) at 60℃; for 0.5 h;
General procedure: A mixture of aromatic aldehyde (1 mmol), ethyl acetoacetate/acetophenone/cyclopentanone (1 mmol) and urea(1.5 mmol) was treated at 60 °C under neat condition (orsolvent-less grinding method using mortar and pestle atambient temperature) utilizing 3 mg of 20percent loaded [Dsim][CF3COO]/NaY composite for the appropriate time untilthe reaction was complete. The progress of the reactionwas monitored with thin layer chromatography in presenceof EtOAc and petroleum ether (1:2) as mobile phase. Themixture was diluted with hot ethanol (3 mL) to dissolvethe crude product. The catalyst was recovered as pure solidresidue after filtration of ethanol solution and then washedthree times with hot ethanol. The product was isolated assolid precipitate after addition of water to the ethanol solutionwith vigorous stirring. Recrystallization of the crudeproduct from saturated ethanol gave analytically pureproduct.
94%
With 1,4-bis(triphenylphosphonium)-2-butene peroxodisulfate In acetonitrile for 0.333333 h; Reflux
General procedure: A mixture of ethyl aceto-acetate(1.0 mmol) with aldehyde (1.0 mmol), urea (1 mmol), and 1,4-bis(triphenylphosphonium)-2-butene peroxodisulfate(0.2 mmol) in acetonitrile was refluxed for20 min. Upon completion of the reaction water wasadded, and the solid product was filtered off, washe dwith ice-cold water, dried, and recrystalized from thanol.
94%
at 100℃; for 0.583333 h; Green chemistry
General procedure: A mixture of aromatic aldehyde (1.0 mmol), β-keto ester(1.0mmol), and urea (2mmol) was reacted at 100 °C usingthe n-Fe3O4(at)ZrO2/HPW (0.003 g, 15 molpercent) under solvent-free conditions for an appropriate time until the reactionwas completed. The reaction progress was monitoredby TLC [7:3 n-hexane: acetone]. After completion of thereaction, the mixture was diluted using hot ethanol and thereaction mixture was separated from the catalyst by meansof an external magnet. At last, the organic solvent wasevaporated under reduced pressure and the resulting solid crude product was then crystallized from hot ethanol toproduce the pure product.
94%
With tris(pentafluorophenyl)borate In ethanol for 3 h; Reflux; Green chemistry
General procedure: A mixture of benzaldehyde 1a (106 mg, 1 mmol), ethyl acetoacetate 2a (130 mg, 1 mmol) and urea 3a (90 mg,1.5 mmol) in EtOH (10 mL) was refluxed in the presence of B(C6F5)3 (18.1 mg, 1 molpercent). After completion of reaction, as indicated by TLC analysis, the solvent was evaporated. The resulting mass was treated with ice-cold water and the solid obtained was filtered, washed with cold water, dried and re-crystallized from ethanol to give pure product (4a).
94%
With bis(p-sulfoanilino)triazine-functionalized silica-coated magnetite nanoparticles In neat (no solvent) at 100℃; for 0.75 h;
General procedure: A mixture of aromatic aldehyde (1 mmol), b-keto ester or dimedone (1 mmol) and urea or thiourea (1.2 mmol) was stirred in presence MNPs-BSAT (20 mg) at 100 °C under solvent-free condition for the appropriate time (Scheme 1). After completion of the reaction as indicated by TLC (using n-hexane-ethyl acetate as eluent), the resulting mixture was diluted with hot ethanol (15 mL) and the catalyst separated by an external magnet and washed with hot ethanol (5 mL) two times. The filtrate was cooled to room temperature and the crude products which precipitated were collected and recrystallized from ethanol if necessary.
Reference：
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[66] Journal of Chemical Sciences (Bangalore), 2012, vol. 124, # 4, p. 921 - 926,6
[67] Phosphorus, Sulfur and Silicon and the Related Elements, 2013, vol. 188, # 5, p. 596 - 608
[68] Heterocycles, 2015, vol. 91, # 1, p. 105 - 112
[69] Journal of the Chinese Chemical Society, 2014, vol. 61, # 11, p. 1254 - 1258
[70] Research on Chemical Intermediates, 2016, vol. 42, # 4, p. 3303 - 3314
[71] RSC Advances, 2016, vol. 6, # 112, p. 110928 - 110934
[72] RSC Advances, 2016, vol. 6, # 115, p. 113844 - 113858
[73] RSC Advances, 2017, vol. 7, # 29, p. 17732 - 17740
[74] Research on Chemical Intermediates, 2017, vol. 43, # 5, p. 3325 - 3347
[75] Patent: CN106632073, 2017, A, . Location in patent: Paragraph 0028; 0038; 0039
[76] New Journal of Chemistry, 2017, vol. 41, # 14, p. 6893 - 6901
[77] Synthetic Communications, 2002, vol. 32, # 1, p. 147 - 151
[78] Journal of Chemical Research - Part S, 2003, # 9, p. 544 - 545
[79] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2005, vol. 44, # 4, p. 762 - 767
[80] Molecules, 2006, vol. 11, # 8, p. 649 - 654
[81] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2007, vol. 46, # 10, p. 1690 - 1694
[82] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2007, vol. 46, # 9, p. 1545 - 1548
[83] Journal of Heterocyclic Chemistry, 2008, vol. 45, # 4, p. 1183 - 1185
[84] Phosphorus, Sulfur and Silicon and the Related Elements, 2009, vol. 184, # 9, p. 2333 - 2338
[85] Asian Journal of Chemistry, 2010, vol. 22, # 1, p. 283 - 287
[86] Catalysis Communications, 2011, vol. 15, # 1, p. 123 - 126
[87] Journal of Molecular Catalysis A: Chemical, 2012, vol. 352, p. 75 - 80
[88] Inorganic Chemistry Communications, 2012, vol. 17, p. 58 - 63
[89] Journal of the Korean Chemical Society, 2013, vol. 57, # 2, p. 169 - 171
[90] Catalysis Letters, 2012, vol. 142, # 12, p. 1505 - 1511
[91] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2013, vol. 52, # 8, p. 1161 - 1165
[92] RSC Advances, 2014, vol. 4, # 21, p. 10514 - 10518
[93] Journal of Molecular Catalysis A: Chemical, 2014, vol. 387, p. 45 - 56
[94] Journal of Molecular Catalysis A: Chemical, 2017, vol. 426, p. 198 - 204
[95] Catalysis Letters, 2017, vol. 147, # 3, p. 674 - 685
[96] Russian Journal of General Chemistry, 2017, vol. 87, # 4, p. 842 - 845[97] Zh. Obshch. Khim., 2017, vol. 87, # 4, p. 842 - 845,4
[98] Catalysis Letters, 2017, vol. 147, # 6, p. 1551 - 1566
[99] Journal of Chemical Sciences, 2015, vol. 127, # 6, p. 1047 - 1052
[100] Research on Chemical Intermediates, 2018, vol. 44, # 7, p. 4083 - 4101
[101] Synlett, 2000, # 1, p. 63 - 64
21
[ 141-97-9 ]
[ 104-88-1 ]
[ 17356-08-0 ]
[ 5948-71-0 ]
Yield
Reaction Conditions
Operation in experiment
85%
With bismuth vanadate In neat (no solvent) at 120℃; for 1.5 h; Green chemistry
General procedure: A mixture of the aldehyde, oxime and/or acylal (1 mmol),1,3-dicarbonyl compound (1 mmol), urea (or thiourea)(1.2 mmol) and BiVO4-NPs (30 mg, 9.3 molpercent) was heatedin an oil bath (120 °C) under solvent-free conditions. Aftercompletion of the reaction (monitored by TLC), the reactionmixture was cooled to room temperature and EtOH(5 mL) was added and filtered to separate the catalyst. Thenthe crude product was recrystallized from EtOH to give thepure product
Reference：
[1] Journal of the Iranian Chemical Society, 2017, vol. 14, # 1, p. 75 - 87
22
[ 141-97-9 ]
[ 104-88-1 ]
[ 57-13-6 ]
[ 5948-71-0 ]
Yield
Reaction Conditions
Operation in experiment
59%
at 60℃; for 12 h;
General procedure: To a mixture of aldehyde (2 mmol), ethyl acetoacetate (2 mmol), and either urea, thiourea or guanidine (2.5 mmol) was added ZnO (10 molpercent) or nanoZnO (5 molpercent) and the mixture was stirred at 60 °C under solvent-free conditions for the given times (Table 1). After the completion of the reaction (TLC monitoring), EtOAc (2× 10 mL) was added and the precipitated ZnO was filtered off. The resulting organic solution was washed with 10percent NaHCO3 and brine, dried over anhydrous Na2SO4, and evaporated to give the DHPM product. The products were structurally assigned by their IR, 1H NMR, 13C NMR spectra analysis and comparison to authentic samples.
Reference：
[1] Journal of Molecular Catalysis A: Chemical, 2013, vol. 370, p. 117 - 122
Reference：
[1] Archiv der Pharmazie (Weinheim, Germany), 1987, vol. 320, # 7, p. 647 - 654
29
[ 15184-98-2 ]
[ 104-88-1 ]
[ 104-11-0 ]
Reference：
[1] Journal of the Chemical Society, Chemical Communications, 1985, # 2, p. 64 - 65
[2] Journal of the Chemical Society, Chemical Communications, 1985, # 2, p. 64 - 65
30
[ 683-60-3 ]
[ 104-88-1 ]
[ 18962-05-5 ]
Yield
Reaction Conditions
Operation in experiment
75%
With hemicucurbituril supported [Bmim]Cl In toluene for 10 h; Reflux
General procedure: A mixture of aryl halide (1 mmol) and sodium alkoxide(3.0 mmol) was refluxed in the presence of 200 mg ofHmCucSILP catalyst in toluene (5 mL) for an appropriatetime as indicated in Table 2. After completion of thereaction, the reaction mixture was filtered and solvent wasevaporated in vacuo to give the crude product, which waspurified by column chromatography over silica gel usinghexane/EtOAc as the eluent.
To the mixture of nitrosonitric acid (55 mL) and sulfuric acid (55 mL) was added 4-chlorobenzaldehyde (70 g, 0.5 mol) in batches at 5 °C and stirred for 2 h. Then the mixture was poured slowly to ice water (1 L) while stirring constantly. The resulting precipitate was filtered and recrystallized from ethanol/water to give product 13 (90 g, 97percent) as white acicular crystal. Mp: 62-63 °C
94%
at 0 - 20℃; for 0.5 h; Inert atmosphere
General procedure: 10 mmol of the desired p-substituted benzaldehyde was dissolved in 5 mL of conc. sulfuric acid, and cooled to 0 °C, and then 1.2 equiv. of nitric acid was dissolved in 1 mL of conc. sulfuric acid, and then slowly added to the reaction mixture. The reaction was allowed to warmgradually to room temperature and stirred for 30 min at room temperature. It was then poured into 50 mL of ice-cold water. The produced precipitate was filtered and washed with cold water. The product was purified on reverse phase column chromatography with gradient increase of methanol in water containing 0.1percent of formic acid as eluent.
75%
at 150℃; for 0.025 h; Microwave irradiation
General procedure: The microwave (MW) reactor used was of CEM make, which was equipped with temperature, pressure, and MW power control units. An oven-dried MW vial was charged with a mixture containing aromatic compound, V2O5 (9 mg, 0.005 mmol) and 69percent HNO3 (0.063 mL, 1 mmol) and silica gel slurry, and irradiated in a MW (power input 140 W) at 150 °C for few minutes. After completion of the reaction, as as certained by TLC, the reaction mixture was treated with sodium bicarbonate; the organic layer was diluted with dichloromethane (DCM) and separated from aqueous layer. The crude product mixture was purified with ethyl acetate DCM mixture. The purity was checked with TLC. The products were identified by characteristic spectroscopic data.
70%
at 0 - 40℃; for 1 h;
General procedure: The nitration of aldehydes was carried out in a three-neckedflask of 50 ml with magnetic stirrer. H2SO4 25 ml (0.47 M)were cooled to 0 °C, 3.1 ml (0.070 M) of HNO3 were added,and then the aldehyde (0.06 M) was slowly added. Thereaction was carried out at a temperature of 0–5 °C. Then,the mixture was heated at 40 °C for 1 h. The reaction waspoured into ice water and filtered under a vacuum; thenitrobenzaldehydes were purified by recrystallization. Thescheme of reaction is showed in Fig. 1 (Furniss et al. 1989).The spectrums of 1H NMR of nitrobenzaldehydes wereobtained in CDCl3 and TMS as reference. 4-chloro-3-nitrobenzaldehyde: Yellow solid; mp 60–62 °C; yield: 70percent; 1H NMR (600MHz, CDCl3), 7.89(d, J = 8.16, 1H Ar–H), 8.25 (d, J = 8.16, 1H, Ar–H), 8.98(t, J = 8.16, 1H, Ar–H), 10.01 (s, 1H, –CHO).
Reference：
[1] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 4, p. 657 - 667
[2] European Journal of Medicinal Chemistry, 2014, vol. 77, p. 361 - 377
[3] Journal of Chemical Research, 2008, # 12, p. 722 - 724
[4] Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry, 2013, vol. 43, # 8, p. 977 - 983
[5] Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry, 2014, vol. 44, # 7, p. 921 - 926
[6] Medicinal Chemistry Research, 2018, vol. 27, # 7, p. 1782 - 1791
[7] Supramolecular Chemistry, 2011, vol. 23, # 5, p. 407 - 410
[8] Journal of the Chemical Society, 1927, p. 25
[9] Justus Liebigs Annalen der Chemie, 1897, vol. 294, p. 380
[10] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 3, p. 65
[11] Recueil des Travaux Chimiques des Pays-Bas, 1926, vol. 45, p. 694[12] Recueil des Travaux Chimiques des Pays-Bas, 1929, vol. 48, p. 1137
[13] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 3, p. 63
[14] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 3, p. 63
[15] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 3, p. 64
[16] Fortschr. Teerfarbenfabr. Verw. Industriezweige, vol. 3, p. 63
32
[ 104-88-1 ]
[ 790-41-0 ]
Yield
Reaction Conditions
Operation in experiment
35%
With tert.-butylhydroperoxide; copper dichloride In decane; acetonitrile at 80℃; for 5 h;
General procedure: General procedure: The oxidative self-coupling reaction was carried out in atwo-necked round bottomed ask tted with a condenser under an airatmosphere. In a typical experiment, a mixture of aromatic aldehyde (1 mmol)and CuCl2 (13 mg, 10 mol percent) in MeCN (2 mL) was placed in the ask at roomtemperature. Then, TBHP (in decane (5-6 M), 1.5 equiv) was added to thereaction mixture slowly over a 5 min period, and the mixture was placed in anoil bath with magnetic stirring at 80 °C. After completion (TLC), the reactionmixture was cooled to room temperature and ethyl acetate (10 mL) andaqueous saturated NaHCO3 (10 mL) were added. The organic layer wascollected and dried with Na2SO4. The solvent was removed under reducedpressure. The residue was puried by column chromatography on silica gel(petroleum ether/ethyl acetate, 9:1) to afford the pure product.
Reference：
[1] RSC Advances, 2018, vol. 8, # 43, p. 24203 - 24208
[2] Tetrahedron Letters, 2016, vol. 57, # 5, p. 566 - 569
[3] New Journal of Chemistry, 2017, vol. 41, # 3, p. 931 - 939
[4] Tetrahedron Letters, 2017, vol. 58, # 26, p. 2533 - 2536
33
[ 104-88-1 ]
[ 790-41-0 ]
[ 74-11-3 ]
Reference：
[1] Chemical and Pharmaceutical Bulletin, 2007, vol. 55, # 1, p. 156 - 158
Reference：
[1] European Journal of Organic Chemistry, 2017, vol. 2017, # 16, p. 2379 - 2384
36
[ 104-88-1 ]
[ 2420-26-0 ]
Reference：
[1] Chemistry - A European Journal, 2015, vol. 21, # 33, p. 11735 - 11744
37
[ 106-43-4 ]
[ 2420-26-0 ]
[ 5306-98-9 ]
[ 615-74-7 ]
[ 104-88-1 ]
[ 873-76-7 ]
Reference：
[1] Journal of the Chemical Society. Perkin Transactions 2, 1996, vol. 4, p. 551 - 556
38
[ 104-88-1 ]
[ 5445-25-0 ]
Reference：
[1] Journal of Medicinal Chemistry, 1993, vol. 36, # 23, p. 3738 - 3742
[2] Tetrahedron, 1986, vol. 42, # 8, p. 2275 - 2282
39
[ 899426-20-1 ]
[ 75-08-1 ]
[ 16251-45-9 ]
[ 36056-25-4 ]
[ 104-88-1 ]
Reference：
[1] Chemistry - A European Journal, 2006, vol. 12, # 14, p. 3896 - 3904
40
[ 110-89-4 ]
[ 104-88-1 ]
[ 10338-57-5 ]
Yield
Reaction Conditions
Operation in experiment
83%
With water; sodium t-butanolate In toluene at 105℃; for 5 h; Schlenk technique
General procedure: An oven-dried Schlenk tube was charged with the aryl halide (2 mmol) and amine (2.5 mmol), FeOA–Pd (0.05 g, 0.04 mmol, 1.5 molpercent), base (3 mmol), solvent (5 mL) and additive. The resulting mixture was stirred for the appropriate time and temperature. After reaction completion the reaction mixture was then cooled to room temperature and the catalyst separated using a magnet, taken up in Et2O (4 mL), and washed with brine (5 mL). The resulting solution was dried over anhydrous MgSO4, filtered and concentrated. The crude product was purified by flash chromatography on silica gel.
Reference：
[1] Journal of Medicinal Chemistry, 2002, vol. 45, # 16, p. 3549 - 3557
[2] Journal of the Indian Chemical Society, 2013, vol. 90, # 10, p. 1853 - 1860
[3] Chinese Chemical Letters, 2016, vol. 27, # 4, p. 555 - 558
[4] Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 7, p. 1849 - 1853
42
[ 104-88-1 ]
[ 14548-38-0 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2005, vol. 15, # 5, p. 1333 - 1336
[2] Letters in Drug Design and Discovery, 2014, vol. 11, # 5, p. 578 - 585
[3] Letters in Drug Design and Discovery, 2018, vol. 16, # 2, p. 111 - 118
Reference：
[1] Bulletin de la Societe Chimique de France, 1994, vol. 131, p. 1031 - 1034
46
[ 558-13-4 ]
[ 541-41-3 ]
[ 104-88-1 ]
[ 20026-96-4 ]
Reference：
[1] Journal of Chemical Research, 2018, vol. 42, # 4, p. 206 - 209
47
[ 104-88-1 ]
[ 20026-96-4 ]
Reference：
[1] Chemical Communications, 2014, vol. 50, # 100, p. 15864 - 15866
48
[ 104-88-1 ]
[ 43141-66-8 ]
Reference：
[1] Journal of Fluorine Chemistry, 2001, vol. 111, # 2, p. 153 - 160
[2] Chemische Berichte, 1988, vol. 121, p. 1329 - 1340
[3] Synthesis, 1973, p. 787 - 789
[4] Patent: WO2009/121939, 2009, A2, . Location in patent: Page/Page column 58-59
49
[ 104-88-1 ]
[ 536-74-3 ]
[ 57341-98-7 ]
Yield
Reaction Conditions
Operation in experiment
92%
With nickel(II) ferrite; potassium carbonate In water at 100℃; for 3 h;
General procedure: In a round-bottom flask equipped with a condenser for refluxingand a magnetic stirring bar, aryl/alkyl halide (1 mmol), phenylacetylene (1 mmol), K2CO3 (1.1 mmol), nickel ferrite nanoparticles(0.05 mmol) and water (3 ml) were added and heated at 100 °Cunder air atmosphere. The mixture was vigorously stirred underthese reaction conditions and its completion was monitored byTLC (EtOAc–n-hexane, 25:75).In each case, after completion of the reaction, the mixturewas dilutedwith diethyl ether and water. The organic layer was washed withbrine, dried over MgSO4, and concentrated under reduced pressureusing a rotary evaporator. The residue was purified by recrystallizationfrom ethanol and water.
91%
With 1,4-diaza-bicyclo[2.2.2]octane; tetrabutylammomium bromide In N,N-dimethyl acetamide at 120℃; for 48 h;
General procedure: Aryl halide and a terminal alkyne, with an equivalent molar ratioof 1.0–1.5, were added to a mixture of PdbisindoleSiO2Fe3O4(0.18 mmol, 20 mg) and DABCO (2.0 mmol, 224 mg) in a flask and2 mL DMA was added. The reaction mixture was stirred at 60C foraryl iodides and aryl bromides. The reaction temperature was setto 120C for aryl chlorides and 1 mmol TBAB was also added. Theprogress of the reaction was monitored by gas chromatography.After completion of the reaction, distilled water (2 mL) was addedto the reaction mixture and the crude product was extracted withethyl acetate (3 × 5.0 mL). The crude product was further purifiedby column chromatography using n-hexane and ethyl acetate as eluents.
80%
With C59H51BrOP4Pd(2+)*3CF3O3S(1-); caesium carbonate In methanol at 60℃; for 24 h;
General procedure: A mixture of an aryl halide (1 mmol), phenylacetylene (1.3 mmol), Cat. (0.001 molpercent), Cs2CO3 (2.5 mmol), and methanol (3 ml) was heated to 60 °C for 24 h. The reaction mixture was then cooled to room temperature and the solvent was removed under reduced pressure. The combined organic extracts were washed with brine and dried over CaCl2 and MgSO4. The solvent was evaporated and coupling product was obtained. The liquid residues were purified by silica gel column chromatography (n-hexane:EtOAc, 80:20) and the solid residues were purified by re-crystallization from ethanol and water.
78%
With C37H29ClN3PPdS; triethylamine In N,N-dimethyl-formamide at 20℃; for 24 h;
General procedure: In an oven-dried round bottom flask, a mixture of aryl halide (1 mmol), phenylacetylene (1.5 mmol), complex 1 (0.5 mol percent for aryl bromides, 1.0 mol percent for aryl chlorides) and Et3N (3.0 mmol) in DMF (5 mL) was taken. The reaction mixture was stirred at room temperature (12 h for aryl bromides, 24 h for aryl chlorides). At the end of the time period mentioned, the reaction mixture was diluted with EtOAc (20 mL) and washed with water (3 x 10 mL). The organic layer was dried over anhydrous Na2SO4, filtered and stripped off the solvent under reduced pressure. The residue was subjected to column chromatography on silica gel using ethyl acetate and n-hexane mixtures to afford the desired product in high purity. The products were characterized by 1H and 13C NMR analysis.
74%
With [PdCl2((C6H5)2PCH2P(C6H5)2CHC(O)C6H4NO2)]; potassium carbonate In N,N-dimethyl-formamide at 130℃; for 10 h;
General procedure: A mixture of an aryl halide (1 mmol), phenylacetylene(1.3 mmol), catalyst (0.001 mol percent), K2CO3 (2.5 mmol), and DMF(2 ml) was heated to 130 C. The mixture was then cooled to roomtemperature and the solvent was removed under reduced pressure.The combined organic extracts were washed with brine and driedover CaCl2 or MgSO4. The solvent was evaporated and liquid residueswere purified by silica gel column chromatography (n-hexane:EtOAc, 80:20) and solid residues were purified byrecrystallization from EtOH and H2O. Products were identified bycomparison of their 1H and 13C NMR spectral data those reportedin the literature.
72%
at 150℃; for 24 h;
General procedure: To slurry of aryl halide (1 mmol), cuprous iodide (10 molpercent) andpalladium catalyst (a known molpercent) in an appropriate solvent(4 mL), phenylacetylene (1.2 mmol) and NaOH (1.7 mmol) wasadded and heated at required temp. After completion of the reaction(monitored by TLC), the flask was removed from the oil bathand water (20 mL) added, followed by extraction with ether(4 10 mL). The combined organic layers were washed with water(3 10 mL), dried over anhydrous Na2SO4, and filtered. Solventwas removed under vacuum. The residue was dissolved in hexaneand analyzed by GC–MS using Elite-5 columns, which are fused silicacapillary columns coated with 5percent diphenyl and 95percent dimethylpolysiloxane.
69%
With potassium carbonate In N,N-dimethyl-formamide at 100℃; for 16 h; Green chemistry
General procedure: A mixture of aryl halide (1mmol), terminal alkyne (1mmol), K2CO3 (2mmol) and MNPFemTriazNHCAg complex (6) (100mg) in DMF (5mL) was stirred at 100°C. The progress of reaction was monitored by TLC. After completion, the reaction mixture was quenched in ice cold water and 6 was separated by external magnet. The reaction mixture was extracted with ethyl acetate (3×25mL). Evaporation of solvent in vaccuo followed by column chromatography over silica gel using petroleum ether/ethyl acetate afforded desired Sonogashira coupling products.
15 %Chromat.
With copper(l) iodide; C18H14N2Pd; sodium hydroxide In ethanol; toluene at 25℃; for 24 h;
General procedure: To slurry of aryl halide (1 mmol), cuprous iodide (10 molpercent) and palladium catalyst (a known molpercent) in 1:1 ethanol–toluene (4 mL), phenylacetylene (1.2 mmol) and NaOH (1.7 mmol) were added and heated at 25 °C. After completion of the reaction (monitored by TLC), the flask was removed from the oil bath and water (20 mL) added, followed by extraction with ether (4 × 10 mL). The combined organic layers were washed with water (3 × 10 mL), dried over anhydrous Na2SO4, and filtered. Solvent was removed under vacuum. The residue was dissolved in hexane and analyzed by GC–MS.#10;
Reference：
[1] Catalysis Communications, 2014, vol. 60, p. 82 - 87
[2] Applied Catalysis A: General, 2016, vol. 525, p. 31 - 40
[3] RSC Advances, 2015, vol. 5, # 92, p. 75263 - 75267
[4] European Journal of Organic Chemistry, 2007, # 21, p. 3445 - 3448
[5] Catalysis Science and Technology, 2015, vol. 5, # 7, p. 3501 - 3506
[6] Catalysis Communications, 2013, vol. 37, p. 114 - 121
[7] Tetrahedron Letters, 2015, vol. 56, # 37, p. 5252 - 5256
[8] Journal of Fluorine Chemistry, 2008, vol. 129, # 11, p. 1124 - 1128
[9] Tetrahedron Letters, 2013, vol. 54, # 35, p. 4656 - 4660
[10] Inorganica Chimica Acta, 2015, vol. 425, p. 67 - 75
[11] Dalton Transactions, 2017, vol. 46, # 44, p. 15235 - 15248
[12] Dalton Transactions, 2017, vol. 46, # 38, p. 13065 - 13076
[13] Journal of Organometallic Chemistry, 2018, vol. 866, p. 112 - 122
[14] Tetrahedron Letters, 2006, vol. 47, # 18, p. 3023 - 3026
[15] Chemical Communications, 2002, # 8, p. 818 - 819
[16] New Journal of Chemistry, 2017, vol. 41, # 7, p. 2745 - 2755
[17] Organic and Biomolecular Chemistry, 2006, vol. 4, # 1, p. 111 - 115
[18] Journal of Organometallic Chemistry, 2013, vol. 736, p. 1 - 8
[19] European Journal of Inorganic Chemistry, 2013, # 26, p. 4654 - 4661
[20] Journal of Chemical Sciences, 2015, vol. 127, # 4, p. 597 - 608
50
[ 1719-19-3 ]
[ 104-88-1 ]
[ 57341-98-7 ]
Yield
Reaction Conditions
Operation in experiment
86%
With tetrabutylammomium bromide; potassium carbonate; palladium dichloride; XPhos In water at 120℃; Inert atmosphere; Schlenk technique; Green chemistry
General procedure: To a 25-mL Schlenk tube equipped with magnetic stir bar, aryl chloride (0.2 mmol), aryl propargylic alcohol (0.3 mmol), K2CO3 (2.0 equiv.), TBAB (1.0 equiv.), PdCl2 (2 molpercent), and Xphos (4 molpercent) were added in turn, then 2 mL H2O was added, and then the solution was refluxed for 24 h under N2 atmosphere. After the reaction was completed, the mixture was extracted with EtOAc or CH2Cl2. The combined organic layer was dried with anhydrous Na2SO4 and evaporated in vacuum. The crude product was purified by flash chromatography on silica gel using hexane/ethyl acetate as the eluent to afford the desired product.
Reference：
[1] Patent: US2792418, 1954, ,
[2] Journal of the American Chemical Society, 1959, vol. 81, p. 5733,5735
[3] Tetrahedron Asymmetry, 2005, vol. 16, # 14, p. 2475 - 2485
[4] Bioorganic and Medicinal Chemistry Letters, 2006, vol. 16, # 4, p. 845 - 849
54
[ 104-88-1 ]
[ 35271-74-0 ]
Reference：
[1] MedChemComm, 2015, vol. 6, # 4, p. 671 - 676
[2] Patent: CN106187794, 2016, A,
55
[ 67-56-1 ]
[ 104-88-1 ]
[ 13726-16-4 ]
Reference：
[1] Journal of the Indian Chemical Society, 2011, vol. 88, # 5, p. 727 - 730
56
[ 104-88-1 ]
[ 4619-18-5 ]
Reference：
[1] Patent: EP259085, 1988, A1,
57
[ 104-88-1 ]
[ 134-83-8 ]
Reference：
[1] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 10, p. 2519 - 2525
58
[ 104376-24-1 ]
[ 104-88-1 ]
[ 7295-50-3 ]
Reference：
[1] Angewandte Chemie - International Edition, 2011, vol. 50, # 48, p. 11465 - 11469
59
[ 104-88-1 ]
[ 6212-33-5 ]
Yield
Reaction Conditions
Operation in experiment
34%
Stage #1: With water; ammonium chloride In methanol at 20℃; for 2 h; Stage #2: With hydrogenchloride In water; toluene for 24 h; Reflux
A solution of 4-chlorobenzaldehyde (4.79 g, 34.08 mmol) inmethanol (10 mL) was added dropwise under vigorous stirring to a solution of KCN (2.48 g, 38.08 mmol) and NH4Cl (2.04 g,38.08 mmol) in water (10 mL). The reaction mixture was vigorously stirred at room temperature for 2 h. Then, water (25 mL) was added and the resulting mixture was extracted with toluene (25 mL). The aqueous layer was discarded and the toluene phase was extracted with 6N aqueous HCl (3 × 10 mL). The combined aqueous phasewas refluxed for 24 h. After that, the reaction mixture was evaporated and the resulting residue was suspended in water. The pHwas adjusted to 6–7 by means of the addition of small portions ofNa2CO3to precipitate the amino acid. The (4-chlorophenyl)glycinewas filtered and dried (2.16 g, 11.62 mmol, 34percent yield) and used inthe next step without further purification. Thionyl chloride (1.79 mL, 24.59 mmol) was added dropwiseto an ice-cooled suspension of (4-chlorophenyl)glycine (2.16 g,11.62 mmol) in dry methanol (29 mL). The resulting solution wasstirred at room temperature for 24 h. Then, the solvent was con-centrated under vacuum and the residue was lyophilized to afforda white solid (2.55 g, 10.80 mmol, 93percent yield). Mp 196–198C (lit.194–197C [10]);1H NMR (D2O, 400 MHz) (, ppm) 7.54–7.50 (m,2H, C6H4), 7.46–7.41 (m, 2H, C6H4), 5.30 (s, 1H, CH), 3.81 (s, 3H,CH3);13C NMR (D2O, 100 MHz) (, ppm) 169.2 (C), 135.9 (C), 129.7(2 x CH), 129.6 (2 x CH), 129.5 (C), 55.7 (CH3), 53.9 (CH); HRMS (ESI-TOF) calc. for [C9H11ClNO2]+requires 200.0473, found 200.0464.
Reference：
[1] Journal of Molecular Catalysis A: Chemical, 2017, vol. 426, p. 407 - 418
60
[ 104-88-1 ]
[ 6212-33-5 ]
Reference：
[1] Science China Chemistry, 2013, vol. 56, # 1, p. 117 - 123
61
[ 104-88-1 ]
[ 67336-19-0 ]
Reference：
[1] Organic Preparations and Procedures International, 2005, vol. 37, # 1, p. 65 - 73
[2] Tetrahedron Letters, 1989, vol. 30, # 31, p. 4109 - 4110
62
[ 104-88-1 ]
[ 67336-19-0 ]
[ 43189-37-3 ]
Reference：
[1] Advanced Synthesis and Catalysis, 2012, vol. 354, # 17, p. 3327 - 3332
With ammonium acetate In ethanol at 75 - 80℃; for 8 h;
To 25 mL of ethanol were added 5.00 g (35.6 mmol) of 4-chlorobenzaldehyde, 3.70 g (35.6 mmol) of malonic acid and 4.10 g (53.2 mmol) of ammonium acetate, and the mixture was reacted while stirring under reflux (75 to 80°C) for 8 hours. After completion of the reaction, the obtained reaction mixture was stirred at room temperature for 1 hour and then filtered to give 5.9 g of 3-amino-3-(4-chlorophenyl)propionic acid (racemic mixtures) (isolation yield based on 4-chlorobenzaldehyde: 82.3percent) as white powder. Incidentally, physical properties of the 3-amino-3-(4-chlorophenyl)propionic acid (racemic mixtures) were as follows. 1H-NMR (δ (ppm), D2O) : 2.93 (dd, 1H, J=17.1, 6.8Hz), 3.04 (dd, 1H, J=17.1, 7.8Hz), 4.63 (dd, 1H, J=7.8, 6.8Hz), 7.22 (s, 1H), 7.24 (s, 1H), 7.47 (s, 1H), 7.49 (s, 1H) 13C-NMR (δ (ppm), D2O) : 40.4, 53.9, 126.0, 131.9, 135.3, 137.1, 175.9 MS (EI) m/z: 199 (M+) MS (CI, i-C4H10) m/z: 200 (MH+)
75%
With ammonium acetate In butan-1-olReflux
General procedure: A mixture of appropriate aldehyde 2.40 g (1-15), 2.44 g ofmalonic acid and 3.54 g of ammonium acetate (1:1.1:2.3), in 200mLof the 1-butanol was refluxed for 1.5-2 h until the evolution of CO2ceased. The precipitate formed was filtered and washed withboiling 1-butanol (2 x 50 mL), boiling ethanol (2 x 50 mL) and100mL of water. Precipitates were dried at 80-100 °C for 8-10 h.Purity of product was checked by TLC, and yield obtained about65-80percent in each reaction.
Reference：
[1] Patent: EP1621529, 2006, A1, . Location in patent: Page/Page column 31
[2] Preparative Biochemistry and Biotechnology, 2013, vol. 43, # 2, p. 207 - 216
[3] European Journal of Medicinal Chemistry, 2018, vol. 156, p. 252 - 268
[4] Advanced Synthesis and Catalysis, 2017, vol. 359, # 9, p. 1570 - 1576
[5] Heterocycles, 1989, vol. 28, # 2, p. 1015 - 1035
[6] Advanced Synthesis and Catalysis, 2010, vol. 352, # 2-3, p. 395 - 406
[7] Journal of the American Chemical Society, 1946, vol. 68, p. 1137
[8] Arzneimittel-Forschung/Drug Research, 2005, vol. 55, # 5, p. 259 - 264
[9] Angewandte Chemie - International Edition, 2005, vol. 44, # 45, p. 7466 - 7469
[10] Journal of Medicinal Chemistry, 2001, vol. 44, # 12, p. 1938 - 1950
[11] European Journal of Organic Chemistry, 2013, # 3, p. 557 - 565
[12] Bulletin of the Chemical Society of Japan, 2013, vol. 86, # 7, p. 870 - 879
[13] Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 6, p. 1356 - 1365
Reference：
[1] Journal of the American Chemical Society, 2012, vol. 134, # 28, p. 11667 - 11673
76
[ 104-88-1 ]
[ 43189-20-4 ]
Reference：
[1] Journal of Molecular Catalysis A: Chemical, 2017, vol. 426, p. 407 - 418
77
[ 67-56-1 ]
[ 143-33-9 ]
[ 104-88-1 ]
[ 43189-20-4 ]
Reference：
[1] Journal of the American Chemical Society, 1978, vol. 100, p. 8190 - 8202
78
[ 1885-46-7 ]
[ 104-88-1 ]
[ 73960-07-3 ]
Yield
Reaction Conditions
Operation in experiment
49%
Stage #1: With tris-(dibenzylideneacetone)dipalladium(0); potassium hydroxide; tert-butyl XPhos In 1,4-dioxane; water at 100℃; Inert atmosphere Stage #2: With potassium hydroxide In 1,4-dioxane; water; acetonitrile at 20℃; for 0.0333333 h;
General procedure: [a] Reactions were performed on a 0.5 mmol scale to determine yields by 19F NMR spectroscopy with PI1CF3 as an internal standard added after the reaction.; Note: The hydroxylation reaction was set-up under an inert atmosphere according to the literature procedure. [Anderson, K. W.; Ikawa, T.; Tundel, R. E.; Buchwald, S. L. J. Am. Chem. Soc. 2006, 128, 10694.] To an oven-dried 4 mL vial was added Pd2(dba)3 (9.2 mg, .010 mmol, 4.0 mol percent Pd), 2-Di-tert-butylphosphino-2',4',6'-triisopropylbiphenyl (lBu- XPhos, 17.0 mg, .040 mmol, 8.0 mol percent), KOH (1.0-3.0 equiv), degassed H20 (150-300 μ) and dioxane (250-500 μΚ). The aryl halide (0.5 mmol, 1.0 equiv) was added (solid aryl halides were weighed into the vial prior to adding solvent, and liquid aryl bromides were added neat by syringe after the addition of solvent). The vial was sealed with a Teflon-lined cap and heated at 100 °C for 1-18 h. The solution was allowed to cool, and the reaction was diluted with acetonitrile (500-750 μ, such that the total volume of dioxane and acetonitrile is 1.0 mL) and 6M KOH (700-850 μ, such that the final aqueous solvent volume is 1.0 mL). The resulting mixture was stirred rapidly at room temperature, and HCF20Tf (210 μ, 1.5 mmol, 3.0 equiv) was added at once. Note: the reactions are exothermic. The mixture was stirred vigorously for 2 minutes. The reaction was diluted with ]0 (8 mL) and extracted with ether (2 x 8 mL). The combined organic layers were dried over MgS04, concentrated, and purified by silica gel chromatography.
Stage #1: at 120℃; for 3 h; Stage #2: at 170℃; for 12 h;
General procedure: This is an adapted protocol for previous research carried out bydifferent authors.8 A suspension of a previously distilled benzaldehyde1a–h (50 mmol) and ammonium acetate (150 mmol) washeated at 120 C, and stirred for 3 h. After this time, the reactionwas cooled to room temperature, and the gummy residue waswashed with hexane. The resulting crude was basified with anaqueous 4 M NaOH solution (pH >10) and extracted with Et2O(4 20 mL). The organic phases were combined, dried, and filtered,and the solvent was evaporated under reduced pressure.Without further purification, the resulting intermediate was suspendedin an aqueous 50percent H2SO4 solution (40 mL), and the mixturewas heated overnight at 170 C. The reaction was then cooleddown in an ice-bath with stirring, and H2O (20 mL) was slowlyadded. The resulting solution was warmed until room temperatureand extracted with Et2O (4 60 mL). The aqueous phase was thenneutralized with a concentrated aqueous ammonia solution, andthen extracted with Et2O (4 60 mL). The organic phases werecombined, dried, and filtered, and the solvent was evaporated underreduced pressure, to give the corresponding meso-diamine 2a–h as a white, yellow, or brown solid (40–98percent isolated yield,Table 1).4.2.3 meso-1,2-Bis(4-chlorophenyl)-1,2-ethanediamine 2c Yellow solid (3.43 g, 98percent isolated yield). Rf (60percent MeOH/EtOAc): 0.47; mp: 126-128 °C; IR (KBr): νmax/cm-1 3380, 2950, 1202, 1600, 980, and 820; δH (300.13 MHz, CDCl3, Me4Si): 1.53 (br s, 4H), 4.00 (s, 2H), 7.27-7.34 (m, 8H); δC (75.5 MHz, CDCl3, Me4Si): 62.0 (2CH), 128.5 (4CH), 128.9 (4CH), 133.4 (2C), 140.9 (2C); MS (ESI+, m/z): 281.0 [(M+H)+, 100percent]; HRMS (ESI+, m/z) calcd for C14H15Cl2N2 (M+H)+: 281.0607 found: 281.0592 (35Cl,35Cl), 283.0563 (35Cl,37Cl).
Reference：
[1] Tetrahedron Asymmetry, 2014, vol. 25, # 4, p. 381 - 386
[2] Journal of the Chemical Society, 1957, p. 4407
[3] Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 18, p. 5454 - 5461
[4] Patent: US9988368, 2018, B1,
[5] Journal of Medicinal Chemistry, 2018, vol. 61, # 16, p. 7245 - 7260
[6] Patent: CN108610332, 2018, A,
80
[ 104-88-1 ]
[ 276866-90-1 ]
Yield
Reaction Conditions
Operation in experiment
40%
at 20℃; for 1.5 h;
Iodines (1.12 g, 4.4 mmol), and sodium iodates (400mg, 2.2 mmol) are put into the reaction container in which the sulfuric acid (30 ml) is contained and it 30 min.is stirred in at a room temperature. Thereafter, 4- chlorobenzaldehydes (1.40 g, 10.0 mmol) are additionally put and it is stirred in at a room temperature for 1 hour.The reaction mixture is poured into the iced water after the reaction completion and the then generated solidis filtered and until the product is neutralized it washeswith water. After the solid filtered was melted in ethanol it recrystallized and intended compound 1.06 gs (4.00 mmol, 40percent) were obtained.
Reference：
[1] Bulletin of the Chemical Society of Japan, 2000, vol. 73, # 4, p. 951 - 956
[2] Tetrahedron, 2004, vol. 60, # 41, p. 9113 - 9119
[3] Synthesis, 2006, # 7, p. 1195 - 1199
[4] Patent: KR2016/149561, 2016, A, . Location in patent: Paragraph 0125; 0126; 0127
[5] European Journal of Medicinal Chemistry, 2016, vol. 123, p. 180 - 190
81
[ 3153-32-0 ]
[ 104-88-1 ]
[ 87661-20-9 ]
Reference：
[1] Chemistry - A European Journal, 2002, vol. 8, # 18, p. 4234 - 4240
82
[ 104-88-1 ]
[ 89-98-5 ]
[ 60767-69-3 ]
Reference：
[1] Patent: DE98229, , ,
83
[ 624-45-3 ]
[ 104-88-1 ]
[ 73257-49-5 ]
Yield
Reaction Conditions
Operation in experiment
84%
With ammonium acetate In neat (no solvent) at 55℃; for 3 h; Green chemistry
General procedure: Polyhydroquinolines and DihydropyridinesA mixture of aldehyde (1 mmol), β-dicarbonyl compound (1or 2 mmol), NH4OAc (2.5 mmol), dimedone (1 mmol, whenused), and SBA-15/NHSO3H (5 molpercent) was stirred at 55 °C.After complete disappearance of starting material asindicated by TLC, the resulting mixture was diluted with hotEtOAc (10 mL) and filtered. The catalyst was completelyrecovered from the residue
With iron supported on copper/Zeolite Socony Mobil-5 nanocatalyst In water at 20℃; Sonication
General procedure: In a typical experiment, aromatic aldehyde (1 mmol), bketoester(2 mmol), ammonium acetate (1 mmol), and Fe-Cu/ZSM-5 (3 wtpercent) in 2 ml water were introduced in a 20-mL heavy-walled pear-shaped two-necked flask with nonstandard-tapered outer joint. The flask was attached to a12-mm tip diameter probe, and the reaction mixture was sonicated at ambient temperature at 20 percent power of the processor. After completion of the reaction (monitored byTLC, within 5–8 min), the solid product was filtered,washed with water and ethanol, dried, and recrystallized from ethanol. The supported reagent was washed thrice with water and ethanol and dried under vacuum before reuse.
Reference：
[1] Journal of the Iranian Chemical Society, 2016, vol. 13, # 2, p. 267 - 277
85
[ 104-88-1 ]
[ 105-45-3 ]
[ 73257-49-5 ]
Yield
Reaction Conditions
Operation in experiment
95%
at 80℃; for 0.3 h;
General procedure: A mixture of the alkyl or aryl aldehyde (1 mmol), -dicarbonyl(2 mmol) and ammonium acetate (1.5 mmol) in the presence ofFe3O4NPs (0.024 g, equal to 10 molpercent) was heated at 80C, withstirring. The progress of the reaction was monitored by TLC (elu-ent: EtOAc:n-hexane). After completion of the reaction, the mixturewas cooled to room temperature and then ethanol was added tothe resulting mixture and separated Fe3O4NPs by a normal mag-net. After evaporation of solvent, the solid product was filtered andrecrystallized from ethanol to give the pure products in 72–95percentyields based on the starting aldehyde.
95%
With C23H3BF16N2O; ammonium acetate In toluene at 100℃; for 10 h;
In a 100 mL single-necked flask, 0.01 molpercent of Lewis acid-base bifunctional catalyst I was added (where Rf = CF3R1,R2, R3, R4, R5, R6 = F), 0.1 mol of p-chlorobenzaldehyde (R7 = 4-Cl-Ph), 0.1 mol of methyl acetoacetate (R8 = Me;Me), 0.1 mol of ammonium acetate, 10 mL of toluene, and the reaction was stirred at 100 ° C for 10 hours. TLC followed the reaction to complete the reaction. anti-The yield of the product II (R7 = 4-Cl-Ph; R8 = Me; R9 = Me) was 95percent; the catalyst system was reused 10 timesAfter its catalytic performance did not decline
94%
for 2.25 h; Heating; Green chemistry
General procedure: A mixture of aldehyde 1 (1 mmol), 1,3-dicarbonyl compound 2 (2 mmol), and nitrogen source 3 (3 mmol) were mixed and heated in the presence of a low-melting sugar mixture.The progress of the reaction was monitored by thin-layer chromatography (TLC) using n-hexane–ethyl acetate (7:3) as the solvent system. The Rf values of the product spots ranged from 0.5 to 0.6. After completion of the reaction, water was added to the reaction mixture to obtain the solid product as a precipitate. In cases where the product was obtained as a melt, several washings with water followed by bicarbonate solution gave crystalline products. The solids were filtered and washed with cold water. In most of the cases, the product obtained was pure, and when impure, the product was recrystallized from hot ethanol. Further two products were obtained as oils (Table 5, entries 4w and 4x). These products were extracted with ethyl acetate and dried over anhydrous Na2SO4. Evaporation of the solvent gave the pure product as an oil.
91%
at 100℃; for 0.25 h; Green chemistry
General procedure: To a glassy reactor equipped with a magnetic stir bar, amixture of aromatic aldehyde (1.0 mmol), β-keto ester(2 mmol), ammonium acetate (1.5 mmol) and n-Fe3O4(at)ZrO2/HPW (0.003 g, 15 mol percent) was added. The reactorwas put in an oil bath with the temperature of 100 °C andthe reaction was carried out under solvent-free condition.The progress of the reaction was monitored using TLCplates. When the reaction was completed, the mixture wasallowed to cool to room temperature. Afterwards, the mixturewas triturated with 5mL ethyl acetate and the catalystwas separated by the help of an external magnet. Then thesolvent was evaporated and the crude product was recrystallizedfrom EtOH/H2O to offer the pure product.
90%
With uranyl nitrate hexahydrate; ammonium acetate In ethanol at 20℃; for 0.416667 h; Sonication
General procedure: To a solution of aldehyde (1.0 mmol), ethyl/methyl acetoacetate/acetylacetone (2.0 mmol) and ammonium acetate (1.0 mmol) in ethanol (3 mL), uranyl nitrate (10 molpercent) was added and the resultant reaction mixture was sonicated at room temperature for the required time (Table 1). The progress of the reaction was monitored by TLC. After completion of the reaction, the mixture was poured into crushed ice. The obtained solid was filtered, washed thoroughly with water, dried, and purified by recrystallisation in ethanol.
84%
at 55℃; for 3 h; Green chemistry
General procedure: A mixture of aldehyde (1 mmol), β-dicarbonyl compound (1or 2 mmol), NH4OAc (2.5 mmol), dimedone (1 mmol, whenused), and SBA-15/NHSO3H (5 molpercent) was stirred at 55 °C.After complete disappearance of starting material asindicated by TLC, the resulting mixture was diluted with hotEtOAc (10 mL) and filtered. The catalyst was completelyrecovered from the residue.
74%
With C21H38N(1+)*Mo11O40PV(4-)*3H(1+); ammonium acetate In ethanol at 78℃; for 8 h; Green chemistry
General procedure: The reaction was performed in a round bottom flask, whichwas equipped with a condenser and immersed in an oil bath. A mixture of methylacetoacetate (232 mg, 2 mmol), 2-nitrobenzaldehyde(151 mg, 1 mmol), ammonium acetate(100 mg, 1.3 mmol), and the selected catalyst (30 mg,1.5 percent mmol), in ethanol (8 mL) was thoroughly mixed andthen heated at 78 °C for 8 h. (to the end point of the reaction,checked by TLC). On cooling, the reaction mixture wasfiltered to separate the catalyst, the ethanol was evaporated,and the crude 1,4-dihydropyidine obtained was dried undervacuum (25 °C). The solid catalyst was washed with hexane(2 x 1 mL) and then, H2O (2 x 1 mL). The crude productwas recrystallized to give the pure 1,4-dihydropyridine.
Reference：
[1] RSC Advances, 2014, vol. 4, # 100, p. 56658 - 56664
[2] Tetrahedron Letters, 2010, vol. 51, # 8, p. 1187 - 1189
[3] Advanced Synthesis and Catalysis, 2012, vol. 354, # 10, p. 2001 - 2008
[4] Journal of Molecular Catalysis A: Chemical, 2014, vol. 382, p. 99 - 105
[5] Patent: CN107141249, 2017, A, . Location in patent: Paragraph 0114; 0115
[6] Synthetic Communications, 2016, vol. 46, # 24, p. 1989 - 1998
[7] RSC Advances, 2014, vol. 4, # 21, p. 10514 - 10518
[8] Journal of the Indian Chemical Society, 2009, vol. 86, # 9, p. 996 - 1000
[9] New Journal of Chemistry, 2018, vol. 42, # 15, p. 12539 - 12548
[10] Journal of Heterocyclic Chemistry, 2008, vol. 45, # 3, p. 737 - 739
[11] Catalysis Letters, 2017, vol. 147, # 6, p. 1551 - 1566
[12] Chemical Communications, 2011, vol. 47, # 32, p. 9230 - 9232
[13] Research on Chemical Intermediates, 2015, vol. 41, # 9, p. 6877 - 6883
[14] Journal of the Chinese Chemical Society, 2016, vol. 63, # 4, p. 336 - 344
[15] Synthesis, 2007, # 18, p. 2835 - 2838
[16] Organic Preparations and Procedures International, 2012, vol. 44, # 2, p. 153 - 158
[17] Synthetic Communications, 2004, vol. 34, # 23, p. 4349 - 4357
[18] Synthetic Communications, 2009, vol. 39, # 11, p. 1957 - 1965
[19] Chinese Journal of Chemistry, 2011, vol. 29, # 1, p. 118 - 122
[20] RSC Advances, 2014, vol. 4, # 37, p. 19111 - 19121
[21] Journal of Chemical Sciences, 2012, vol. 124, # 5, p. 1091 - 1096
[22] Medicinal Chemistry Research, 2013, vol. 22, # 1, p. 147 - 155
[23] Synlett, 2014, vol. 25, # 19, p. 2753 - 2756
[24] Canadian Journal of Chemistry, 2017, vol. 95, # 5, p. 530 - 536
[25] Asian Journal of Chemistry, 2012, vol. 24, # 12, p. 5649 - 5651,3
[26] Transition Metal Chemistry, 2010, vol. 35, # 1, p. 125 - 127
[27] Catalysis Letters, 2016, vol. 146, # 9, p. 1634 - 1647
[28] Chemical Communications, 2010, vol. 46, # 42, p. 8052 - 8054
[29] Journal of the Brazilian Chemical Society, 2011, vol. 22, # 3, p. 525 - 531
[30] Journal of Medicinal Chemistry, 1988, vol. 31, # 11, p. 2103 - 2107
[31] Organic Process Research and Development, 2001, vol. 5, # 4, p. 452 - 455
[32] Synthesis, 2006, # 8, p. 1283 - 1288
[33] Indian Journal of Chemistry, Section B: Organic Chemistry Including Medicinal Chemistry, 1995, vol. 34, # 10, p. 920 - 922
[34] Synthetic Communications, 2010, vol. 40, # 16, p. 2457 - 2463
86
[ 105025-71-6 ]
[ 104-88-1 ]
[ 73257-49-5 ]
Reference：
[1] Journal of Materials Chemistry A, 2013, vol. 1, # 37, p. 11210 - 11220
Reference：
[1] Angewandte Chemie - International Edition, 2013, vol. 52, # 24, p. 6277 - 6282[2] Angew. Chem., 2013, vol. 125, # 24, p. 6397 - 6402,6
97
[ 104-88-1 ]
[ 131690-60-3 ]
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[1] Preparative Biochemistry and Biotechnology, 2013, vol. 43, # 2, p. 207 - 216
98
[ 104-88-1 ]
[ 73183-34-3 ]
[ 128376-64-7 ]
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[1] Journal of Organic Chemistry, 2012, vol. 77, # 7, p. 3543 - 3548
[2] RSC Advances, 2018, vol. 8, # 25, p. 13643 - 13648
[3] Organic Letters, 2002, vol. 4, # 4, p. 541 - 543
[4] Tetrahedron, 2001, vol. 57, # 49, p. 9813 - 9816
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[ 128796-39-4 ]
[ 104-88-1 ]
[ 90035-34-0 ]
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[1] New Journal of Chemistry, 2016, vol. 41, # 1, p. 372 - 376
[2] Organic Process Research and Development, 2012, vol. 16, # 1, p. 117 - 122
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[1] Advanced Synthesis and Catalysis, 2015, vol. 357, # 14-15, p. 3255 - 3261
108
[ 6456-74-2 ]
[ 104-88-1 ]
[ 1216744-19-2 ]
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[1] Journal of Medicinal Chemistry, 2013, vol. 56, # 11, p. 4729 - 4737
109
[ 104-88-1 ]
[ 1112209-14-9 ]
Reference：
[1] Journal of the American Chemical Society, 2016, vol. 138, # 1, p. 84 - 87
[2] Journal of the American Chemical Society, 2016, vol. 138, # 1, p. 84 - 87
With ammonium acetate; In ethanol; at 75 - 80℃; for 8h;
To 25 mL of ethanol were added 5.00 g (35.6 mmol) of 4-chlorobenzaldehyde, 3.70 g (35.6 mmol) of malonic acid and 4.10 g (53.2 mmol) of ammonium acetate, and the mixture was reacted while stirring under reflux (75 to 80°C) for 8 hours. After completion of the reaction, the obtained reaction mixture was stirred at room temperature for 1 hour and then filtered to give 5.9 g of 3-amino-3-(4-chlorophenyl)propionic acid (racemic mixtures) (isolation yield based on 4-chlorobenzaldehyde: 82.3percent) as white powder. Incidentally, physical properties of the 3-amino-3-(4-chlorophenyl)propionic acid (racemic mixtures) were as follows. 1H-NMR (delta (ppm), D2O) : 2.93 (dd, 1H, J=17.1, 6.8Hz), 3.04 (dd, 1H, J=17.1, 7.8Hz), 4.63 (dd, 1H, J=7.8, 6.8Hz), 7.22 (s, 1H), 7.24 (s, 1H), 7.47 (s, 1H), 7.49 (s, 1H) 13C-NMR (delta (ppm), D2O) : 40.4, 53.9, 126.0, 131.9, 135.3, 137.1, 175.9 MS (EI) m/z: 199 (M+) MS (CI, i-C4H10) m/z: 200 (MH+)
75%
With ammonium acetate; In butan-1-ol;Reflux;
General procedure: A mixture of appropriate aldehyde 2.40 g (1-15), 2.44 g ofmalonic acid and 3.54 g of ammonium acetate (1:1.1:2.3), in 200mLof the 1-butanol was refluxed for 1.5-2 h until the evolution of CO2ceased. The precipitate formed was filtered and washed withboiling 1-butanol (2 x 50 mL), boiling ethanol (2 x 50 mL) and100mL of water. Precipitates were dried at 80-100 °C for 8-10 h.Purity of product was checked by TLC, and yield obtained about65-80percent in each reaction.
With ammonium acetate; In ethanol; at 78℃;
General procedure: Benzaldehyde (1 equiv), propanedioic acid (2 equiv) and ammonium acetate (2 equiv) were added to the solution of anhydrous ethanol (30 mL) and heated to 78 °C for 17 h. A lot of precipitated solid was filtered and dried in vacuo at 40 °C for 24 h to give a light white solid.
Example 1OA; tert-butyl {3-[(4-chlorobenzyl)amino]propyl}carbamate EPO <DP n="29"/>10 g (71.1 mmol) 4-chlorobenzaldehyde and 13.6 g (78.3 mmol) tert-butyl (2-aminopropyl)- carbamate are dissolved in 200 ml methanol and stirred for 2 h at room temperature. The solution is cooled to O0C and 13.5 g (355.7 mmol) sodium borohydride are carefully added. Water is added until a clear solution is formed and the mixture is stirred at room temperature overnight. The mixture is concentrated under vacuum, the residue is diluted with dichloromethane and the organic phase is washed with brine, dried over magnesium sulfate and concentrated under vacuum. The crude product is re-crystallized from petroleum ether to yield 8.9 g (42percent of th.) of the title compound as a solid.HPLC (method 6): R, = 4.03 min; MS (ESIpos): m/z = 299 (M+H)+1H-NMR (300 MHz, DMSOd6): delta = 7.35 (m, 4H), 6.70 (m, IH), 3.60 (s, 2H), 2.95 (m, 2H), 2.40 (m, 2H), 2.10 (bs, IH), 1.50 (m, 2H), 1.40 (s, 9H).
With magnesium sulfate; In acetonitrile; at 20℃;Reflux;
To a stirred mixture of 4-chlorobenzaldehyde (2.3 g, 16.1 mmol) and anhydrous magnesium sulfate (16 g, 134 mmol) in anhydrous acetonitrile (200 ml) was added <strong>[59434-19-4]4-aminoisobenzofuran-1(3H)-one</strong> (2 g, 13.4 mmol) at room temperature. After the addition, the mixture was stirred at reflux for overnight. The mixture was filtered and the cake was washed with ethyl acetate (50 mL×3). The filtrate was concentrated to give crude product. The crude product was washed with petroleum ether and re-crystallized from ethyl acetate to give the title compound (2 g, yield: 55%). LC-MS (ESI) m/z: 272 (M+1)+.
55%
With magnesium sulfate; In acetonitrile; at 20℃;Reflux;
Example 105A(E)-4-(4-Chlorobenzylideneamino)isobenzofuran- 1 (3H)-one[00704] To a stirred mixture of 4-chlorobenzaldehyde (2.3 g, 16.1 mmol) and anhydrous magnesium sulfate (16 g, 134 mmol) in anhydrous acetonitrile (200 ml) was added 4-aminoisobenzofuran- l (3H)-one (2 g, 13.4 mmol) at room temperature. After the addition, the mixture was stirred at reflux for overnight. The mixture was filtered and the cake was washed with ethyl acetate (50 mL x 3). The filtrate was concentrated to give crude product. The crude product was washed with petroleum ether and re- crystallized from ethyl acetate to give the title compound (2 g, yield: 55%). LC-MS (ESI) m/z: 272 (M+l)+.
With sodium tris(acetoxy)borohydride; acetic acid; In dichloromethane; at 20℃;
Example 2) l-MethyI-lH-pyrazoIe-3-sulfonic acid (4-chloro-benzyl)-(2-ethyl-l- oxo-1 ,2,3,4-tetrahydro-isoquinolin-7-yl)-amide (METHOD B)i) 7-Benzylamino-3,4-dihydro-2H-isoquinolin-l-one Sodium triacetoxyborohydride (1.29 g, 6.16 mmol) was added to a stirred solution of 7-amino-3,4-dihydro-2H-isoquinolin-l-one (500 mg, 3.08 mmol), 4- chlorobenzaldehyde (431 mg, 3.0S mmol) and acetic acid (183 mul, 3.08 mmol) in anhydrous dichloromethane (25 ml) at room temperature. The reaction was stirred overnight and quenched with the addition of water. The organic phase was separated, washed with brine, then dried (MgSO4) and evaporated in vacuo. The resulting residue was purified by flash column chromatography (50% ethyl acetate in dichloromethane) to yield the title compound as a pale yellow solid (287 mg, 16%). HPLC retention time 4.09min. Mass spectrum (ES+) m/z 287 (M+H).
With sulfuric acid; In acetic acid; at 20℃; for 192.0h;
(3E,5E)-5-[(4-chlorophenyl)methylidene]-3-[(4-nitrophenyl)methylidene]azepan-4-one (compound No. 1583). <strong>[19869-42-2]N-methylazepan-4-one hydrochloride</strong> (75 mg, 0.46 mmol) and4-chlorobenzaldehyde (64 mg, 0.46 mmol) were dissolved in acetic acid (7 mL) and stirred for 10 min, then cone. H2S04 (350 mu?) was added slowly and the mixture was stirred at rt for 8 days. More cone. H2S04 was added during days 2-4 (0.175 mL, 0.35 mL, 0.25 mL respectively). Water (2 x reaction volume) was added and the solution extracted with ethyl acetate (2 x reaction volume). The organic phase was concentrated to give Intermediate 8. A portion of the intermediate (35 mg, 0.14 mmol) and 4-nitrobenzaldehyde (69.5 mg, 0.46 mmol) were dissolved in acetic acid (2.5 mL) and stirred for 10 min, then cone. H2S04 (200 mu?) was added slowly and the mixture was stirred at rt for 5 days. More cone. H2S04 (0.2 mL) was added, and stirring continued for 5 more days. Water (2 x reaction volume) was added and the solution extracted with ethyl acetate (2 x reaction volume). The organic phase was concentrated and the residue purified by preparative LC to give the title compound (1.8 mg) as a yellow solid of 94percent purity. LCMS System A: Rt 1.98/2.04 m/z[M+H]+ 383.1, System B: Rt 2.82/2.98.
(4-chlorophenyl)-(3-methyl-3H-imidazol-4-yl)methanol[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
Step 1 (4-Chloro-phenyl)-(3-methyl-3H-imidazol-4-yl)-methanol In a 10 mL two-necked flask, 5-iodo-l-methyl-lH-imidazole (150 mg, 721 muiotaetaomicron, Eq: 1.00) was combined with DCM (3 ml) to give a colorless solution. Ethylmagnesium bromide (264 mu, 793 muiotaetaomicron, Eq: 1.1) was added at rt over 2min (white precipitate). After stirring for lhr, the reaction mixture was cooled to 0C, and a solution of 4- chlorobenzaldehyde (132 mg, 937 muiotaetaomicron, Eq: 1.3) in DCM (2 ml) was added dropwise, and the mixture was stirred at rt. TLC after 2 h indicated the absence of starting material. Work up: The reaction mixture was quenched with sat. NaHC03 (10 mL) and extracted with AcOEt (2 x 20 mL). The organic layers were washed with H20/NaCl sol., the organic layers were combined, dried over Na2S04, and concentrated i. V. The product was precipitated from DCM, filtered and dried on h. V. MS (ESI): 223.1/225.0 [M+H]+. The reaction can equally well be performed in THF or a mixture of THF and DCM.
In a 10 mL two-necked flask, <strong>[71759-88-1]5-iodo-1-methyl-1H-imidazole</strong> (150 mg, 721 mumol, Eq: 1.00) was combined with DCM (3 ml) to give a colorless solution. Ethylmagnesium bromide (264 mul, 793 mumol, Eq: 1.1) was added at rt over 2 min (white precipitate). After stirring for 1 hr, the reaction mixture was cooled to 0 C., and a solution of 4-chlorobenzaldehyde (132 mg, 937 mumol, Eq: 1.3) in DCM (2 ml) was added dropwise, and the mixture was stirred at rt. TLC after 2 h indicated the absence of starting material. Work up: The reaction mixture was quenched with sat. NaHCO3 (10 mL) and extracted with AcOEt (2*20 mL). The organic layers were washed with H2O/NaCl sol., the organic layers were combined, dried over Na2SO4, and concentrated i. V. The product was precipitated from DCM, filtered and dried on h. V. MS (ESI): 223.1/225.0 [M+H]+.
With potassium hydroxide; In methanol; ethanol; at 0 - 20℃; for 0.5h;
General procedure: A 0.5 N KOH solution (0.5 N in CH3OH, 6.0 mL, 3.0 mmol) was added to a mixture of 3c (467 mg, 3.0 mmol) and 4-methoxybenzaldehyde (408 mg, 3.0 mmol) in EtOH (15 mL) at 0 °C. The mixture was stirred for 0.5 h between 0 °C and room temperature. The resulting yellow solution containing white precipitate was quenched with 0.5 N HCl solution (6 mL). After evaporating the solvent, the mixture was poured into saturated NH4Cl solution (30 mL), extracted with dichloromethane(3 × 20 mL), and washed with brine (30 mL). The combined organic phases were dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The residue was recrystallized twice in 5percent EtOAc/n-hexane to give 4ck (673mg, 82percent).
5-(4-chlorophenyl)-1,3-diethyl-8-(methylthio)-2-thioxo-2,3,7,10-tetrahydropyrido[2,3-d:6,5-d’]dipyrimidine-4,6(1H,5H)-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
98%
With hydroxyapatite-encapsulated-gamma-Fe2O3 supported sulfonic acid nanoparticles; In ethanol; for 0.05h;Reflux; Green chemistry;
General procedure: A mixture of 6-amino-2-(alkylthio)pyrimidin-4(3H)-one 5 (1 mmol),1,3-diethyl-2-thioxodihydropyrimidine-4,6(1H,5H)-dione 6 (1 mmol),arylaldehyde (1 mmol) and [gamma-Fe2O3HAp-SO3H] (0.05 g) in EtOH (10 mL) was heated under reflux. The progress of the reaction was monitored by TLC (EtOAc/petroleum: 2/1). After completion ofthe reaction, the catalyst was separated from the reaction mixture by external magnet and reused in the next run. The reaction mixture was cooled, and the solid obtained was recrystallised from EtOH/H2O to give the desired pure product.
2-(2-(4-chlorobenzylidene)hydrazino)-6-fluorobenzothiazole[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
79%
With acetic acid; In ethanol; at 80℃; for 0.166667h;Microwave irradiation;
General procedure: A mixture of compound 2 (0.0549 g, 0.0003 mol), the appropriate aromatic aldehyde (0.00033 mol) and glacial acetic acid (0.1 mL) in ethanol (5 mL) was heated under microwave (20 W) at 80 °C for 10 min. On cooling, the precipitated solid was collected by filtration, washed with water, dried and crystallized to give compounds 3-29.
In ethanol; at 70 - 80℃; for 3h;
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).
cis-2-(4-chlorobenzenyl)-3-phenyl-oxirane[ No CAS ]
[ 28291-10-3 ]
Yield
Reaction Conditions
Operation in experiment
General procedure: Ammonium salt 6 (1 equiv.) was suspended in dry THF (0.05 M) andstirred at 40 °C. t-BuOK (4 equiv.) was added and the mixture was stirred vigorously. After 10 minutes 2 equiv. of aldehyde 2 were added and the mixture was stirred for 3 hours at 40 °C. The reaction was then quenched by addition of a half-saturated NaCl solution. After phase separation, the aqueous phase was extracted three times with DCM and the combined organic phases were dried with Na2SO4 and evaporated to dryness. Purification by columnchromatography (gradient of heptanes and EtOAc) gave the corresponding epoxides in the reported yields as a mixture of diastereomers.
With ZnBr2/SiO2; In neat (no solvent); for 0.0833333h;Microwave irradiation; Green chemistry;
General procedure: The mixture of 4-(4-chlorophenoxy)aniline (2) (220 mg,1.0 mmol), 3-nitrobenzaldehyde (3e) (155mg, 1.03 mmol),diethyl phosphite (4) (0.13 mL, 1.0 mmol) and SiO2-ZnBr2 (17.1 mg, 6 molpercent) were taken into a flask. Thereaction mass was irradiated with microwave radiationsfor 4 min using Catalyst systems (CATA-4R,), percentpower is 65percent and 465Watts. Ethyl acetate (10 mL) wasadded to the reaction mixture and stirred for 10 min,after completion of the reaction as checked by TLC.The catalyst, SiO2-ZnBr2 was separated by filtrationas residue, washed with ethyl acetate (2×5mL) andcollected residue was dried under vacuum at 100°C toutilize in further reactions. The combined organic layerwas washed with water (10 mL), dried over anhydrousNa2SO4 and concentrated under vacuum at 50°C toobtain crude mass. The pure compound, diethyl (4-(4-chlorophenoxy)phenylamino)(3-nitrophenyl)methylphosphonate (5e) was isolated by column chromatographyusing 20?60percent ethyl acetate:n-hexane as a mobilephase.
5-(4-chlorobenzylamino)-[1,3,4]thiadiazole-2-carboxylic acid ethyl ester[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
44 mg
With sodium tris(acetoxy)borohydride; trifluoroacetic acid; In isopropyl alcohol; at 20 - 70℃; for 18h;
A suspension of 5-amino-[1 ,3,4]thiadiazole-2-carboxylic acid ethyl ester (0.30 g, 1 .75 mmol), TFA (0.27 mL, 3.50 mmol), 4-chlorobenzaldehyde (0.27 g, 1 .93 mmol) and sodium triacetoxyborohydride (0.45 g, 2.10 mmol) in isopropanol (3.5 mL) was stirred at room temperature for 2 hours and then at 70°C for 1 6 hours. After this time the reaction mixture wasconcentrated under reduced pressure and purified by flash column chromatography, eluting with EtOAc/cyclohexane (0-50percent) to afford the title compound (44 mg). LCMS method: Method 3, RT: 4.81 mm, Ml: 298 [M+1] 1H NMR (500 MHz, CDCI3) O 7.32 (d, 2H), 7.29 (d, 2H), 4.53 (5, 2H), 4.41 (q, 2H), 1 .39 (t, 3H)
dimethyl (4-chlorophenyl)(2-methyl-3-(trifluoromethyl)phenylamino)methylphosphonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
96%
With chitosan; In neat (no solvent); at 75℃; for 0.05h;Microwave irradiation; Green chemistry;
General procedure: An equimolar mixture of <strong>[54396-44-0]2-methyl-3-(trifluoromethyl)aniline</strong> (0.351 g, 0.002 mol), corresponding aldehyde (0.002 mol), dimethyl phosphite (0.18 ml, 0.002 mol) and chitosan catalyst (10 molpercent) were taken in a reaction glass tube, degassed for 10 min and microwave irradiated at 180 W for 2 min at 60 °C. The progress of the reaction was monitored by TLC using petroleum ether and ethyl acetate (3:7) as solvent. After completion of the reaction, the mixture was diluted with ethyl acetate, washed with water (2 x 15 ml) followed by brine (1 x 10 ml), dried over Na2SO4 and evaporated to dryness. The crude mass was purified by column chromatography on silicagel (100-200 mesh) by using a 7:3 mixture of ethyl acetate in hexane to afford the pure alpha-aminophosphonates.
(+)-di-isopropyl 2-((4-chlorophenyl)((4-(pyridin-3-yl)pyrimidin-2-yl)amino)methyl)malonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
90%
With 3-((3,5-bis(trifluoromethyl)phenyl)amino)-4-(((S)-(6-methoxyquinoline-4-yl))((1S,2S,4S,5R-5-vinylquinuclidine-2-yl)methyl)amino)cyclobutan-3-ene-1,2-dione; In neat liquid; at 50℃; for 48h;
General procedure: Reactions were carried out with <strong>[66521-66-2]4-(pyridin-3-yl)pyrimidin-2-amine</strong> 1 (0.50 mmol), aldehyde 2 (0.50 mmol) and malonate 3 (5 mmol) in the presence of catalyst III or IV (10 molpercent) at 50 °C and stirred for 48h. After completion of the reaction (as observed by TLC), the crude product was purified by preparative TLC (GF254 silica gel: hexane/EtOAc = 7/1), giving the target chiral product
(-)-di-isopropyl 2-((4-chlorophenyl)((4-(pyridin-3-yl)pyrimidin-2-yl)amino)methyl)malonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
94%
With quinine; In neat liquid; at 50℃; for 48h;
General procedure: Reactions were carried out with <strong>[66521-66-2]4-(pyridin-3-yl)pyrimidin-2-amine</strong> 1 (0.50 mmol), aldehyde 2 (0.50 mmol) and malonate 3 (5 mmol) in the presence of catalyst III or IV (10 molpercent) at 50 °C and stirred for 48h. After completion of the reaction (as observed by TLC), the crude product was purified by preparative TLC (GF254 silica gel: hexane/EtOAc = 7/1), giving the target chiral product
(+)-diethyl 2-((4-chlorophenyl)((4-(pyridin-3-yl)pyrimidin-2-yl)amino)methyl)malonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
93%
With 3-((3,5-bis(trifluoromethyl)phenyl)amino)-4-(((S)-(6-methoxyquinoline-4-yl))((1S,2S,4S,5R-5-vinylquinuclidine-2-yl)methyl)amino)cyclobutan-3-ene-1,2-dione; In neat liquid; at 50℃; for 48h;
General procedure: Reactions were carried out with <strong>[66521-66-2]4-(pyridin-3-yl)pyrimidin-2-amine</strong> 1 (0.50 mmol), aldehyde 2 (0.50 mmol) and malonate 3 (5 mmol) in the presence of catalyst III or IV (10 molpercent) at 50 °C and stirred for 48h. After completion of the reaction (as observed by TLC), the crude product was purified by preparative TLC (GF254 silica gel: hexane/EtOAc = 7/1), giving the target chiral product
(-)-diethyl 2-((4-chlorophenyl)((4-(pyridin-3-yl)pyrimidin-2-yl)amino)methyl)malonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
92%
With quinine; In neat liquid; at 50℃; for 48h;
General procedure: Reactions were carried out with <strong>[66521-66-2]4-(pyridin-3-yl)pyrimidin-2-amine</strong> 1 (0.50 mmol), aldehyde 2 (0.50 mmol) and malonate 3 (5 mmol) in the presence of catalyst III or IV (10 molpercent) at 50 °C and stirred for 48h. After completion of the reaction (as observed by TLC), the crude product was purified by preparative TLC (GF254 silica gel: hexane/EtOAc = 7/1), giving the target chiral product
(+)-dimethyl 2-((4-chlorophenyl)((4-(pyridin-3-yl)pyrimidin-2-yl)amino)methyl)malonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With 3-((3,5-bis(trifluoromethyl)phenyl)amino)-4-(((S)-(6-methoxyquinoline-4-yl))((1S,2S,4S,5R-5-vinylquinuclidine-2-yl)methyl)amino)cyclobutan-3-ene-1,2-dione; In neat liquid; at 50℃; for 48h;
General procedure: Reactions were carried out with <strong>[66521-66-2]4-(pyridin-3-yl)pyrimidin-2-amine</strong> 1 (0.50 mmol), aldehyde 2 (0.50 mmol) and malonate 3 (5 mmol) in the presence of catalyst III or IV (10 molpercent) at 50 °C and stirred for 48h. After completion of the reaction (as observed by TLC), the crude product was purified by preparative TLC (GF254 silica gel: hexane/EtOAc = 7/1), giving the target chiral product
(-)-dimethyl 2-((4-chlorophenyl)((4-(pyridin-3-yl)pyrimidin-2-yl)amino)methyl)malonate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
95%
With quinine; In neat liquid; at 50℃; for 48h;
General procedure: Reactions were carried out with <strong>[66521-66-2]4-(pyridin-3-yl)pyrimidin-2-amine</strong> 1 (0.50 mmol), aldehyde 2 (0.50 mmol) and malonate 3 (5 mmol) in the presence of catalyst III or IV (10 molpercent) at 50 °C and stirred for 48h. After completion of the reaction (as observed by TLC), the crude product was purified by preparative TLC (GF254 silica gel: hexane/EtOAc = 7/1), giving the target chiral product
7-chloro-2-(4-chlorophenyl)-1,2-dihydroquinazolin-4(3H)-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
95%
With potassium hydroxide; In dimethyl sulfoxide; at 20℃; for 0.75h;
General procedure: 2-Aminobezamides (1 mmol) and substituted aldehydes (1.2 mmol) and 0.2 M solution of KOH in water (2 mL) in DMSO (1 mL) were stirred at room temperature. The progress of the reaction was monitored by TLC under UV light. After completion of the reaction the mixture was extracted with ethyl acetate (3 x 10 mL) and washed with water (3 x 10 mL). The combined extract was dried over anhydrous Na2SO4. The filtrate was concentrated under reduced pressure. The product was purified by column chromatography over silica gel using n-hexane/ethyl acetate (3:1 v/v) as eluent to get the purified product. The products were then characterized by ESI-MS, 1H NMR and 13C NMR spectra.
ethyl-2-(3-bromo-5-fluorobenzylidene)-3-oxobutanoate[ No CAS ]
[ 4568-71-2 ]
[ 104-88-1 ]
ethyl 2-acetyl-3-(3-bromo-5-fluorophenyl)-4-(4-chlorophenyl)-4-oxobutanoate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
With nitrogen; triethylamine;
Synthesis of ethyl 2-acetyl-3-(3-bromo-5-fluorophenyl)-4-(4-chlorophenyl)-4-oxobutanoate To a solution of ethyl-2-(3-bromo-5-fluorobenzylidene)-3-oxobutanoate (46.8 g, 148.5 mmol) and 4-chlorobenzaldehyde (21.4 g, 152.2 mmol) in ethanol (240 mL) was added triethylamine (31 mL, 222 mmol). Nitrogen gas was bubbled through the mixture for 5 min and 3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride (6 g, 22 mmol) was then added. The mixture was heated to 70 C. for 2 h under a nitrogen atmosphere. The solvent was removed under vacuum and the residual crude was dissolved in EtOAc (700 mL) and washed with 1 M aqueous HCl (130 mL), water (2*150 mL) and brine (2*20 mL). The organic extract was dried over MgSO4, filtered and concentrated under vacuum to give ethyl 2-acetyl-3-(3-bromo-5-fluorophenyl)-4-(4-chlorophenyl)-4-oxobutanoate as an orange gum (73.1 g) which was used without purification. LCMS (ESI) [M+Na]+=477.0/479.0
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