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CAS No. : | 121-32-4 | MDL No. : | MFCD00006944 |
Formula : | C9H10O3 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | CBOQJANXLMLOSS-UHFFFAOYSA-N |
M.W : | 166.17 | Pubchem ID : | 8467 |
Synonyms : |
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.22 |
Num. rotatable bonds : | 3 |
Num. H-bond acceptors : | 3.0 |
Num. H-bond donors : | 1.0 |
Molar Refractivity : | 45.15 |
TPSA : | 46.53 Ų |
GI absorption : | High |
BBB permeant : | Yes |
P-gp substrate : | No |
CYP1A2 inhibitor : | No |
CYP2C19 inhibitor : | No |
CYP2C9 inhibitor : | No |
CYP2D6 inhibitor : | No |
CYP3A4 inhibitor : | No |
Log Kp (skin permeation) : | -6.19 cm/s |
Log Po/w (iLOGP) : | 1.82 |
Log Po/w (XLOGP3) : | 1.58 |
Log Po/w (WLOGP) : | 1.6 |
Log Po/w (MLOGP) : | 0.83 |
Log Po/w (SILICOS-IT) : | 1.83 |
Consensus Log Po/w : | 1.53 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -2.04 |
Solubility : | 1.52 mg/ml ; 0.00917 mol/l |
Class : | Soluble |
Log S (Ali) : | -2.17 |
Solubility : | 1.13 mg/ml ; 0.00679 mol/l |
Class : | Soluble |
Log S (SILICOS-IT) : | -2.29 |
Solubility : | 0.842 mg/ml ; 0.00507 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.37 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302-H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* 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.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | at 20℃; for 3 h; | The 3-ethoxy-4-hydroxybenzaldehyde (6.64g, 40 . 0mmol) dissolved in acetic acid (80 ml) in, is fully dissolved. Then the liquid bromine (2.46 ml) is added dropwise to the reaction solution, after the end of dropping, the reaction at room temperature 3 hours, turbid. TLC monitoring after the reaction is ended, filtering to get the solid, the solid will be 50percent ethanol aqueous solution to re-crystallization, to obtain a target compound 1.1 is 7.8g, yield 80percent. |
49% | With bromine In acetic acid for 2 h; | Example 3 3-bromo-5-ethoxy-4-hydroxy-benzaldehyde (intermediate VII-1) preparation. 10 g 3-ethoxy-4-hydroxybenzaldehyde dissolved in 30 ml of acetate, adding dropwisely into the system 3.08 ml of liquid bromine, reaction fluid gradually changed into yellow, after 2 hours the reaction was stopped. Filtering, the filter cake was washed with a small amount of acetic acid to give 7.247 g yellowish colored solid (Intermediate VII-1), a yield of 49percent. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine In dichloromethane at 0℃; for 0.5 h; | Example 8 N- [ 1 -Cyano-2-(7-ethoxy- 1 -hydroxy- 1.3 -dihydro-benzo [c] [ 1.2]oxaborol-6-yloxy )- 1 -meth yl-ethyl -4-trifluoromethoxy-benzamide To a solution of 3-ethoxy-4-hydroxy-benzaldehyde (50.0 g, 0.30 mol) and Et3N (39.2 g, 54 mL, 0.39 mol) in DCM (500 mL) at 0 °C is added CH3COCl (30.6 g, 28 mL, 0.39 mol) at 0°C. After the addition is complete, the reaction mixture is stirred at 0°C for 30 min. Then the filter cake washed with DCM, and the combined filtrate is washed with water and brine, the organic layer is dried over Na2S04 and evaporated to give the desired product (62.0 g, 100percent yield) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate In N,N-dimethyl-formamide at 20 - 40℃; for 2 h; | To a solution of3-ethoxy-4-hydroxy-benzaldehyde (830 mg, 5 mmol) in N'N-dimethylforrnemide (5 mL)was gradually added K2CO3 (20 mg) and then PmBr (6 mmol) was added ata temperature under 40 °C. The mixture was stirred at room temperature for 2 h.The solution was poured into ice-cold water (10 mL) and extracted with diethylether. The organic phase was washed with water and sodium hydroxide and then itwas dried and evaporated to obtain 18 (1.1g, 85percent). Compound 18 was reacted with sophoridine using same proceduredescribed in synthesis of 11−16 to obtain 14-(4-(benzyloxy)-3-ethoxyphenylmethylene)sophoridine (20) (120 mg, 30percent) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With formic acid In water at 130℃; for 6h; Green chemistry; | |
93% | With hydrogenchloride In methanol; water at 20℃; for 3h; Green chemistry; chemoselective reaction; | |
72% | With C18H4BCl3F8; hydrogen; trimethyl orthoformate In tetrahydrofuran at 80℃; for 48h; |
With hydrogenchloride; amalgamated zinc; toluene | ||
With hydrogenchloride; amalgamated zinc; ethanol | ||
(catalytic hydrogenation); | ||
With hydrogen In water at 120℃; for 6h; Autoclave; | 2.4. Catalyst performance evaluation and product analysis General procedure: All catalyst performance evaluation experiments were conductedin a 25 mL stainless steel autoclave (Anhui Kemi MachineryTechnology Co., Ltd) with a pressure gauge, a mechanicalstirrer and an automatic temperature control apparatus. Ina typical experiment, a Teflon vessel loaded with a mixture ofreactants (0.5 mmol), catalyst (30 mg) and H2O (10 ml) was placed into the autoclave, purged three times with N2 to removethe air, pressurized with H2 to a desired level and heated to apre-determined temperature under a constant stirring rate of600 rpm. Once the desired reaction time was reached, the autoclavewas quickly cooled down to room temperature. Thecatalyst and products were then separated from the reactionsolution by centrifugation and ethyl acetate extraction, respectively.For catalyst reusability tests, the centrifugation recoveredcatalyst was washed with water and ethanol several timesand dried under vacuum oven at 60 °C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With bromine; acetic acid; at 20℃; for 3h; | The 3-ethoxy-4-hydroxybenzaldehyde (6.64g, 40 . 0mmol) dissolved in acetic acid (80 ml) in, is fully dissolved. Then the liquid bromine (2.46 ml) is added dropwise to the reaction solution, after the end of dropping, the reaction at room temperature 3 hours, turbid. TLC monitoring after the reaction is ended, filtering to get the solid, the solid will be 50% ethanol aqueous solution to re-crystallization, to obtain a target compound 1.1 is 7.8g, yield 80%. |
49% | With bromine; In acetic acid; for 2h; | Example 3 3-bromo-5-ethoxy-4-hydroxy-benzaldehyde (intermediate VII-1) preparation. 10 g 3-ethoxy-4-hydroxybenzaldehyde dissolved in 30 ml of acetate, adding dropwisely into the system 3.08 ml of liquid bromine, reaction fluid gradually changed into yellow, after 2 hours the reaction was stopped. Filtering, the filter cake was washed with a small amount of acetic acid to give 7.247 g yellowish colored solid (Intermediate VII-1), a yield of 49%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In water; N,N-dimethyl-formamide; at 20 - 60℃; for 3.5h; | To the solution of 3-ethoxy-4-hydroxy-benzaldehyde (83g) in N,N-dimethylformamide (400ml) was gradually added 10 M sodium hydroxide (55 ml) and then benzyl chloride (60ml) was added at a temperature under 40C. The mixture was stirred at room EPO <DP n="30"/>temperature for a half an hour and for 2 hours at 6O0C. The solution was poured into ice- cold water (2 1) and extracted with diethyl ether. The organic phase was washed with water and 5M sodium hydroxide and then it was dried and evaporated. The product was recrystallized from toluene-heptane. 1H NMR (DMSOd6): delta = 1.34 (t, 3H), 4.12 (q, 2H), 5.24 (s, 2H), 7.26 (d, IH), 7.34-7.53 (m, 7H), 9.83 (s, IH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74% | With C44H52CuN8S4(1+)*BF4(1-) In methanol for 4h; Schlenk technique; Reflux; Inert atmosphere; | 4.2 General Procedure for KnoevenagelCondensation Reactions General procedure: In a typical procedure, aldehyde (1 mmol), active methylenegroup compound (1.2 mmol), and catalyst (5 mol%) wereplaced in a Schlenk tube, and then methanol (2 mL) wasadded. The reaction mixture was stirred for 4 h under aerobicconditions. The reaction progress was monitored by TLC.After completion of the reaction, water was added to formthe precipitate. The precipitate was filtered and re-dissolvedin ethyl acetate, followed by flash column chromatographyto remove the catalyst. |
With pyridine; butan-1-ol | ||
With piperidine; butan-1-ol |
With piperidine In ethanol Heating; | ||
100 %Chromat. | With La2O2CO3(0.09)-TiO2 mixed oxide In acetonitrile at 50℃; for 4h; | 2.3 Performance tests General procedure: In a 10mL round-bottomed flask, carbonyl compounds (5mmol), malononitrile (5mmol) and 5mL of acetonitrile (ACN) was taken. Then a amount of the La2O2CO3(x)-TiO2 mixed oxide catalyst was added to above solution and the mixture was heated to 323K. At the end of the reaction, the reaction mixture was cooled to room temperature and the catalyst was recovered by filtration method. Quantitative analysis of various substituted carbonyl compounds derivatives was conducted with an Agilent 6820 GC equipped with a FID. The conversion of carbonyl compounds and selectivity of products were quantified using n-propanol as an internal standard. The conversion of benzaldehyde is determined by the equation of Conv(benzaldehyde)=(C0-Ci)/C0×100%, where C0 is the initial concentration of benzaldehyde and Ci is the real time concentration of benzaldehyde. The selectivity of 2-benzylidenemalononitrile is determined by the equation of Selec(2-benzylidenemalononitrile)=Pi/(C0-Ci)×100%, where Pi is the real time concentration of 2-benzylidenemalononitrile |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate In 1-methyl-pyrrolidin-2-one at 50℃; for 20h; Molecular sieve; | 4.1 1) Synthesis of ethyl vanillin tetra-O-acetyl-β-D-glucopyranoside: To the reaction flask were added α-bromotetraacetylglucose (8.22 g, 20.0 mmol), potassium carbonate (4.14 g, 30.0 mmol), N-methylpyrrolidine (80 mL), and ethyl vanillin (4.98 g, 30.0 mmol). Subsequently, 4A molecular sieve (2.0 g) was added, and the mixture was heated to 50 ° C to stir the reaction for 20 hours. The reaction was followed by TLC. After completion of the reaction, 100 mL of ethyl acetate was added, followed by filtration to remove insolubles. After adding 100 mL of water, the mixture was shaken well and separated to give an organic phase. The organic phase was washed with a saturated aqueous solution of sodium carbonate and brine, and then evaporated. The oil was subjected to column chromatography (petroleum ether: ethyl acetate = 1:1) to obtain 8.43 g of semi-solid semi-liquid, yield 85%.It is ethyl vanillin tetra-O-acetyl-β-D-glucopyranoside. |
59% | With sodium hydroxide; tetrabutylammomium bromide In dichloromethane at 20℃; for 0.75h; | |
32% | With sodium hydroxide; tetrabutylammomium bromide In chloroform for 3h; Heating; |
Stage #1: 4-hydroxy-3-ethoxybenzaldehyde With sodium hydroxide In water at 10℃; for 0.25h; Stage #2: 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide In water; acetone at 20℃; for 24h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76% | With potassium carbonate In N,N-dimethyl-formamide at 65℃; for 15h; | 18 methyl 3-(4-acetamido-1,3-dioxoisoindolin-2-yl)-3-(3,4-dimethoxyphenyl)propionate General procedure: To a reaction flask were added 3-hydroxy-4-methoxybenzaldehyde (5.0 g) and potassium carbonate (4.56 g). The mixture was dissolved with DMF. Iodomethane (3.1 mL) was added in the mixture. The reaction flask was transferred to an oil bath and the mixture was stirred at 65°C for 15 hours. HPLC showed that the reaction was completed. The reaction solution was diluted in ethyl acetate. The resultant mixture was washed with saturated salt water and extracted. The organic phase was collected, dried over anhydrous magnesium sulfate and concentrated to dryness with a water pump at 40°C to give a crude product. The crude product was purified with silica gel column chromatography (eluent: PE : EA = 8 : 1) to give a colorless oily product, i.e. (3,4-dimethoxybenzaldehyde) (4.95 g, HPLC purity: 99.94%). Yield: 90 %. |
With potassium carbonate In ethanol | ||
With potassium carbonate In N,N-dimethyl-formamide at 110℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
81% | With hydrogenchloride at 20℃; for 48h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With triethylamine In dichloromethane at 0℃; for 0.5h; | 8 Example 8 N-[1-cyano-2-(7-ethoxy-1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yloxy)-1-methylethyl]-4-trifluoromethoxybenzamide Example 8 N- [ 1 -Cyano-2-(7-ethoxy- 1 -hydroxy- 1.3 -dihydro-benzo [c] [ 1.2]oxaborol-6-yloxy )- 1 -meth yl-ethyl -4-trifluoromethoxy-benzamide To a solution of 3-ethoxy-4-hydroxy-benzaldehyde (50.0 g, 0.30 mol) and Et3N (39.2 g, 54 mL, 0.39 mol) in DCM (500 mL) at 0 °C is added CH3COCl (30.6 g, 28 mL, 0.39 mol) at 0°C. After the addition is complete, the reaction mixture is stirred at 0°C for 30 min. Then the filter cake washed with DCM, and the combined filtrate is washed with water and brine, the organic layer is dried over Na2S04 and evaporated to give the desired product (62.0 g, 100% yield) as a yellow solid. |
87% | With pyridine In dichloromethane for 1h; Heating; | |
With pyridine In dichloromethane for 1h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With pyridine In diethyl ether at 18 - 23℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With iron(III) chloride hexahydrate; water for 0.6h; Reflux; Green chemistry; | |
77% | In ethanol; water at 80℃; for 15h; | 2-5 Synthesis of 5-(3-Ethoxy-4-hydroxybenzylidene)pyrimidine-2,4,6(1 H,3H,5H)-trione (Compound 18) General procedure: [0139] Compounds 14 to 24, which are 5-(substituted benzylidene)pyrimidine-2,4,6(1 H,3H,5H)-trione analogs, were synthesizes as follows. In detail, in an EtOH (4 mL) and H2O (4 mL) solvent, a suspension including a substituted benzaldehyde (1.44 to 2.60 mmol) and a barbituric acid (0.7 to 1.2 eq.) was heated to a temperature of 80°C. Before the reaction temperature reached 80° C in most cases, the reaction mixture turned into a clean solution. However, during heating (1 to 18 hours), a precipitate was formed, and afier cooling, a precipitate was filtered. In consideration of characteristics of the residual substituted benzaldhehyde, a filter cake was washed with ethanol and/or methylene chloride and water to obtain a target product (yield: 60.3 to 99.3%). [0144] Orange solid; a reaction time of 15 hours; a yield of 77%; a melting point of 244.7-246. 1°C.; 1H NMR (500 MHz,DMSO-d5) ö 11.24 (s, 1H), 11.11 (s, 1H), 10.46 (s, 1H), 8.48(s, 1H), 8.20 (s, 1H), 7.74 (d, 1H, J=8.5 Hz), 6.90 (d, 1H,J=8.5 Hz), 4.08 (q, 2H, J=7.0 Hz), 1.36 (t, 3H, J=7.0 Hz); 13CNMR (100 MHz, DMSO-d5) ö 164.8, 163.1, 156.6, 154.0,150.8, 146.8, 133.2, 124.9, 119.7, 116.1, 114.6, 64.5, 15.2;ERMS (ES) mlz 275 (M-H)-. |
77% | In ethanol; water at 80℃; for 15h; | 2-5 Synthesis of 5-(3-Ethoxy-4-hydroxybenzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione Compounds 14 to 24, which are 5-(substituted benzylidene)pyrimidine-2,4,6(1H,3H,5H)-trione analogs, were synthesizes as follows. In detail, in an EtOH (4 mL) and H2O (4 mL) solvent, a suspension including a substituted benzaldehyde (1.44 to 2.60 mmol) and a barbituric acid (0.7 to 1.2 eq.) was heated to a temperature of 80° C. Before the reaction temperature reached 80° C., in most cases, the reaction mixture turned into a clean solution. However, during heating (1 to 18 hours), a precipitate was formed, and after cooling, a precipitate was filtered. In consideration of characteristics of the residual substituted benzaldhehyde, a filter cake was washed with ethanol and/or methylene chloride and water to obtain a target product (yield: 60.3 to 99.3%). |
77% | In ethanol; water at 80℃; for 15h; | 2.2-5 Synthesis of compounds 2a to 2n and 2A First, a suspension of various aldehydes (1.44-2.60 mmol) and barbituric acid (0.7-1.2 eq.) In EtOH (4 mL) and H2O (4 mL) was heated to 80°C and the precipitate formed was filtered. In consideration of the physical properties of the remaining aldehyde and barbituric acid, the filtrate solid was washed with ethanol and / or methylene chloride and water to obtain the desired product. According to the above synthesis method, in EtOH (4 mL) and H2O (4 mL) 3-ethoxy-4-hydroxybenzaldehyde (1.44-2.60 mmol) And arabicarboxylic acid (0.7-1.2 eq.) Were reacted for 15 hours to give an orange solid compound 2e in 77% yield |
75% | In ethanol Heating; | |
In ethanol Heating; | ||
In butan-1-ol Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70.4% | Stage #1: 4-hydroxy-3-ethoxybenzaldehyde; acetone In ethanol; water at 20℃; for 24h; Stage #2: With hydrogenchloride In ethanol; water | 5 4-(3-Ethoxy-4-hydroxyphenyl)-3-buten-2-one Preparation 5 4-(3-Ethoxy-4-hydroxyphenyl)-3-buten-2-one 10% sodium hydroxide aqueous solution (80ml) was added under stirring to a solution of 3-ethoxy-4-hydroxybenzaldehyde (16.6g, 100mmo1) in acetone (50ml), 95% ethanol (50ml) and water (400ml). The reaction mixture was stirred for 24 hr at room temperature, after the reaction completed, the reaction mixture was neutralized with 6N hydrochloric acid to adjust pH=7.0, the precipitated yellow solid was collected by filtration, washed with water and ethanol successively, dried, and then recrystallized from 95% ethanol to give 14.5g of a yellow crystal, mp: 98-100°C, yield 70.4 %. |
42% | With sodium hydroxide | |
40% | With sodium hydroxide In ethanol at 0 - 25℃; for 24h; |
With sodium hydroxide |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With potassium carbonate; In DMF (N,N-dimethyl-formamide); at 110℃; for 1h; | Dissolve the corresponding aldehyde (1 equiv), 6-CHLORONICOTINONITRILE (1 equiv) and K2CO3 (2.5 equiv) in anhydrous DMF (0.2 M) and heat at about 110 C under nitrogen FBI. ABOUT 1 hour (the reaction can be monitored by tlc). AFTER COOLING DOWN TO RCOM temperature, the reaction mixture is poured into water and extracted with ethyl acetate (3X50 mL). The combined organic layer is dried over NA2S04, filtered and concentrated under vacuum (toluene may be added to aid DMF evaporation). The crude mixture is purified by flash chromatography using hexanes/ethyl acetate (4: 1) as eluant. 6- (2-ETHOXY-4-FONNYL-PHENOXY) nicotinonitrile 90% yield. P 1H NMR (CHCL3-D3) No.: 9.95 (S, 1H, CHO), 8.37 (DD, 1H, J = 2.6, 0.7 HZ), 7.90 (DD, 1H, J = 8.8, 2.6 Hz), 7.50-7. 33 (m, 2H), 7.32 (m, 1H), 7.10 (dd, 1H, J = 8.8, 0.7 Hz), 4.03 (q, 2H, J = 7.0 Hz), 1.14 (t, 3H, J = 7.0 HZ). 13C NMR (CHCL3-D3) No. : 190.9, 164.9, 151.3, 151.7, 146.8, 142.1, 135. 0,124. 8, 123. 1, 116.6, 112.0, 111.6, 104.3, 64.4, 14.3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 40℃; for 2h; | To a solution of3-ethoxy-4-hydroxy-benzaldehyde (830 mg, 5 mmol) in N'N-dimethylforrnemide (5 mL)was gradually added K2CO3 (20 mg) and then PmBr (6 mmol) was added ata temperature under 40 C. The mixture was stirred at room temperature for 2 h.The solution was poured into ice-cold water (10 mL) and extracted with diethylether. The organic phase was washed with water and sodium hydroxide and then itwas dried and evaporated to obtain 18 (1.1g, 85%). Compound 18 was reacted with sophoridine using same proceduredescribed in synthesis of 11-16 to obtain 14-(4-(benzyloxy)-3-ethoxyphenylmethylene)sophoridine (20) (120 mg, 30%) |
With potassium carbonate; In acetonitrile; for 3h;Heating / reflux; | 25 g of 3-ethoxy-4-hydroxybenzaldehyde, 27 g of benzyl bromide, 25 g of potassium carbonate and 250 ml of acetonitrile were mixed, and stirred under condition of reflux for 3 hours. Then the reaction mixture was cooled to room temperature. Ethyl acetate was added to it, and solid was filtered off. The obtained organic layer was concentrated under reduced pressure, the residue was washed bymethyl=tert-butylether and hexane to obtain 36 g of 4-benzyloxy-3-ethoxybenzaldehyde.1H-NMR (CDCl3, TMS) delta (ppm): 9.82 (1H, s), 7.28-7.44 (7H, m), 6.98 (1H, d, J=8.2 Hz), 5.24 (2H, s), 4.18 (2H, q, J=7.0 Hz), 1.49 (3H, t, J=7.0 Hz) | |
With potassium carbonate; In acetonitrile; for 3h;Heating / reflux; | Reference Example 5 25 g of 3-ethoxy-4-hydroxybenzaldehyde, 27 g of benzyl bromide, 25 g of potassium carbonate and 250 ml of acetonitrile were mixed and stirred under reflux for 3 hours. After the reaction mixture was allowed to cool to room temperature, ethyl acetate was added and the mixture was filtered. The resulting filtrate was concentrated under reduced pressure. The residue was washed with tert-butyl methyl ether and hexane to obtain 36 g of 4-benzyloxy-3-ethoxybenzaldehyde. 1H-NMR (CDCl3, TMS) delta (ppm): 9.82 (1H, s), 7.28-7.44 (7H, m), 6.98 (1H, d, J = 8.2 Hz), 5.24 (2H, s), 4.18 (2H, q, J = 7.0 Hz), 1.49 (3H, t, J = 7.0 Hz) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67.1 In analogy to Example 64.1, from 3-ethoxy-4-hydroxy-benzaldehyde and 1-chlor-2-methyl-2-propanol there was obtained 3-ethoxy-4-(2-hydroxy-2-methyl-propoxy)-benzaldehyde. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57.2% | With sodium hydroxide; In ethanol; ethyl acetate; | Example 28 Synthesis of alpha-(3-Ethoxy-4hexyloxyphenyl)-N-tert-butylnitrone A solution of 3-ethoxy-4-hydroxybenzaldehyde (13.28 g, 79.9 mmol) and sodium hydroxide (3.20 g, 79.9 mmol) in ethanol (120 mL) was refluxed for 30 min. To the refluxing solution was added 1-iodohexane (18.6 g, 87.9 mmol) in one portion and reflux was continued for 24 h. The solution was then cooled and the ethanol removed on a rotary evaporator. The residue was dissolved in ethyl acetate and this solution filtered and rotary evaporated. The resulting residue was reacted with N-tert-butylhydroxylamine (6.94 g) in 200 mL of benzene in the presence of p-toluenesulfonic acid (0.8 g) at refluxing temperature for 24 h. After evaporation, the residue obtained was purified by recrystallization from hexanes to give the title compound (11.02 g, 57.2% overall yield) as a solid, m.p. 35.5 C. Spectroscopic data were as follows: IR (KBr, cm-1): 2900 (CH), 1596.2 (C=N), 1361.1 (CH,), 1276.0 (C--O--C) and 1144.8 (N--O). 1 H NMR (CDCl3, 270 MHz): delta=8.38 (1H, d, J=1.7 Hz, phenyl H), 7.45 (1H, dd, J=8.5 & 1.7 Hz, phenyl H), 7.42 (1H, s, nitronyl H), 6.86 (1H, d, J=8.5 Hz, phenyl H), 4.13 (2H, quartet, J=7.0 Hz, CH2), 4.02 (2H, t, J=6.8 Hz, CH2), 1.82 (2H, m, CH2), 1.65 (2H, m, CH2), 1.58 (9H, s, 3 CH3), 1.42 (3H, t, J=7.0 Hz, CH3), 1.31 (4H, m, 2 CH2) and 0.88 (3H, t, J=6.3 Hz, CH3). 13 C NMR (CDCl3, 67.9 MHz): delta=150.8, 148.6, 130.1, 124.4, 123.4, 113.4, 112.6, 70.0, 69.0, 64.4, 31.3, 28.7, 28.0, 25.3, 22.2, 14.4 and 13.6. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium carbonate; In N,N-dimethyl-formamide; | 91d 4-Formyl-2-ethoxyphenoxyacetic acid 4-Hydroxy-3-ethoxybenzaldehyde (5.0 g, 36 mmol), potassium carbonate (5.0 g, 36 mmol), and t-butyl bromoacetate (5.9 mL, 36 mmol) were heated to 55 C. overnight in DMF (35 mL). After removal of solvent, the mixture was extracted with EtOAc and water, then brine. After drying (Na2 SO4), solvent was removed to yield a white solid (9.7 g). mp 90-92.6 C. MS (NH3): 298 (base, M+NH4). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With dmap In dichloromethane at 0℃; for 1h; | D5 Methanesulfonic acid 2-ethoxy-4-formyl-phenyl ester Methanesulfonic acid 2-ethoxy-4-formyl-phenyl ester To a solution of 3-ethoxy-4-hydroxybenzaldehyde (3.0 g, 18.1 mmol, 1.0 equiv; commercially available) and N,N-dimethylaminopyridine (2.87 g, 23.5 mmol, 1.3 equiv) in dichloromethane (10 mL) under Ar at 0° C. was added methanesulfonyl chloride (1.68 mL, 2.48 g, 21.7 mmol, 1.2 equiv). After the reaction mixture was stirred for 1 h, water (100 mL) was added, the solution extracted with dichloromethane (3*50 mL) and the combined organic phases dried over MgSO4. Removal of the solvent by evaporation under reduced pressure provided the title compound in quantitative yield (4.8 g). 1H NMR (300 MHz, CDCl3): 1.42 (t, J=7.0 Hz, 3H), 3.19 (s, 3H), 4.14 (q, J=7.0 Hz, 2H), 7.41 (s, 2H), 7.45 (s, 1H), 9.89 (s, 1H), 13C NMR (75 MHz, CDCl3): δ 14.53, 38.94, 64.99, 112.20, 124.38, 125.17, 136.01, 142.92, 151.63, 190.65. MS (ISP): 245.2 [M+H]+. |
100% | With dmap In dichloromethane at 0℃; for 1h; | Intermediate D24; Methanesulfonic acid 2-ethoxy-4-formyl-phenyl ester; To a solution of 3-ethoxy-4-hydroxybenzaldehyde (3.0 g, 18.1 mmol, 1.0 equiv) and N,N- dimethylaminopyridine (2.87 g, 23.5 mmol, 1.3 equiv) in dichloromethane ( 10 mL) under Ar at 0 0C was added methanesulfonyl chloride ( 1.68 mL, 2.48 g, 21.7 mmol, 1.2 equiv). After the reaction mixture was stirred for 1 h, water ( 100 mL) was added, the solution extracted with dichloromethane (3 x 50 mL) and the combined organic phases dried over MgSCv Removal of the solvent by evaporation under reduced pressure provided the title compound in quantitative yield (4.8 g). 1H NMR (300 MHz, CDCl3): δ 1.42 (t, / = 7.0 Hz, 3H), 3.19 (s, 3H), 4.14 (q, / = 7.0 Hz, 2H), 7.41 (s, 2H), 7.45 (s, IH), 9.89 (s, IH). 13C NMR (75 MHz, CDCl3): δ 14.53, 38.94, 64.99, 112.20, 124.38, 125.17, 136.01, 142.92, 151.63, 190.65. MS (ISP): 245.2 [M+H]+. |
100% | With dmap In dichloromethane at 0℃; for 1h; | 32 To a solution of 3-ethoxy-4-hydroxybenzaldehyde (3.0 g, 18.1 mmol, 1.0 equiv) and N,N-dimethylaminopyridine (2.87 g, 23.5 mmol, 1.3 equiv) in dichloromethane (10 mL) under Ar at 0° C. was added methanesulfonyl chloride (1.68 mL, 2.48 g, 21.7 mmol, 1.2 equiv). After the reaction mixture was stirred for 1 h, water (100 mL) was added, the solution extracted with dichloro-methane (3×50 mL) and the combined organic phases dried over MgSO4. Removal of the solvent by evaporation under reduced pressure provided the title compound in quantitative yield (4.8 g). 1H NMR (300 MHz, CDCl3): δ 1.42 (t, J=7.0 Hz, 3H), 3.19 (s, 3H), 4.14 (q, J=7.0 Hz, 2H), 7.41 (s, 2H), 7.45 (s, 1H), 9.89 (s, 1H). 13C NMR (75 MHz, CDCl3): δ 14.53, 38.94, 64.99, 112.20, 124.38, 125.17, 136.01, 142.92, 151.63, 190.65. MS (ISP): 245.2 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With nitric acid; In water; acetic acid; for 17.0h; | a). 3-Ethoxy-4-hydroxy-5-nitro-benzaldehyde To a solution of 3-ethoxy-4-hydroxybenzaldehyde (5 g) in acetic acid (50 ml) was added nitric acid (1.4 ml) in 2 portions. The resulting suspension was stirred for 17 h. The solid was collected by filtration, washed with water and dried in vacuo.Yield: 5.07 g. | |
With nitric acid; acetic acid; for 17.0h; | Example 14; Propane- 1 -sulfonic acid r5-(3-cvano-2-methyl-5-oxo-7-propyl-l,4,5,6,7,8-hexahvdro- quinolin-4- vD-3 -ethoxy-2-(3 -methoxy-benzyloxy) -phenyll -amide(a). 3-Ethoxy-4-hvdroxy-5-nitro-benzaldehvdeTo a solution of 3-ethoxy-4-hydroxybenzaldehyde (5 g) in acetic acid (50 ml) was added nitric acid (1.4 ml) in 2 portions. The resulting suspension was stirred for 17 h. The solid was collected by filtration, washed with water and dried in vacuo.Yield: 5.07 g. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With potassium carbonate In ethyl acetate; N,N-dimethyl-formamide at 20℃; | 67.67a (67a) 3-Ethoxy-4-(2-methoxyethoxy)benzaldehyde [Show Image] A mixture of 3-ethoxy-4-hydroxybenzaldehyde (5.32 g, 32 mmol), 2-bromoethyl methyl ether (1.5 ml, 16 mmol), potassium carbonate (4.42 g, 32 mmol), tetrabutylammonium iodide (118 mg, 0.32 mmol) and N,N-dimethylformamide (50 ml) was stirred overnight at room temperature. Water was added to the reaction mixture and extraction was performed with ethyl acetate. The separated organic layer was washed with a 0.5N sodium hydroxide aqueous solution, water and brine in that order and dried over anhydrous sodium sulfate. The desiccant was removed by filtration and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate-heptane) to give the title compound as a white solid (2.79 g, yield: 78%). 1H-NMR (400 MHz, CD3OD) δ: 1.47 (t, J = 7.2 Hz, 3H), 3.47 (s, 3H), 3.80-3.84 (m, 2H), 4.14 (q, J = 7.2 Hz, 2H), 4.23-4.26 (m, 2H), 6.99 (d, J = 8.0 Hz, 1H), 7.38-7.42 (m,2H), 9.82 (s, 1H) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | Stage #1: triethyl 2-ethylphosphonoacetate With sodium hydride In tetrahydrofuran at 0℃; for 0.25h; Stage #2: 4-hydroxy-3-ethoxybenzaldehyde In tetrahydrofuran at 20℃; for 72h; | 33.a a-Ethyl 2-[1-(3-ethoxy-4-hydroxyphenyl)meth-(E)-ylidene]butyrate Example 33Synthesis of 2-[1-[2-ethoxy-3'-(3-heptyl-1-methylureido)biphenyl-4-yl]meth-(E)-ylidene]butyric acid a-Ethyl 2-[1-(3-ethoxy-4-hydroxyphenyl)meth-(E)-ylidene]butyrateA solution of 11.8 g (46 mmol) of triethyl 2-phosphonobutyrate in 20 mL of tetrahydrofuran is added to a mixture of 1.8 g (46 mmol) of sodium hydride in 20 mL of tetrahydrofuran at 0° C. The reaction medium is stirred for 15 minutes. A solution of 3.4 g (20 mmol) of 3-ethoxy-4-hydroxybenzaldehyde prepared as in Example 32a in 20 mL of tetrahydrofuran is then added to the reaction mixture and the reaction medium is stirred at room temperature for 3 days. The reaction medium is then poured into saturated ammonium chloride solution, acidified with aqueous 2 N hydrochloric acid solution and extracted with ethyl acetate. The organic phases are combined, washed with water and dried over sodium sulfate. The solvent is evaporated off and the residue (12.5 g) is purified by chromatography on a column of silica eluted with an 80/20 heptane/ethyl acetate mixture. 3.7 g (71%) of ethyl 2-[1-(3-ethoxy-4-hydroxyphenyl)meth-(E)-ylidene]butyrate are obtained in the form of a yellow oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
77% | With aluminum oxide In dichloromethane at 20℃; Reflux; Inert atmosphere; | 4.1.1. General procedure for the synthesis of 2-benzylidenebenzofuran-3(2H)-one (method A) General procedure: To a solution of benzofuran-3(2H)-one (1.0 mmol) and benzaldehyde(1.0 mmol) in dichloromethane (6 mL) was added aluminum oxide (30.0 mmol) at room temperature. After stirring for 6 h, the reaction mixture was filtered off. The filtrate was concentrated under vacuum and the residue was purified by flash chromatography on silica gel to give the desired compound |
68.9% | With aluminum oxide In dichloromethane at 20℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95.2% | With hydroxylamine hydrochloride In acetonitrile for 4h; Reflux; | 1 Example-1: Preparation of 3-ethoxy-4-hydroxybenzonitrile To the round bottom flask, charge Ethyl vanillin (100.0 grams, 0.602 mol), hydroxylamine hydrochloride (50.2 grams, 0.722 mol), and acetonitrile (300 mL). The stirred slurry was heated to reflux for 4 hours. The stirred mixture was allowed to cool at 40-45 °C and distilled off acetonitrile under vacuum. Water (500 mL) was charged to reaction mass and extract with ethyl acetate (2 *300 mL). The combined ethyl acetate layer was washed with 10% sodium chloride solution (200 mL). The ethyl acetate layer was distilled off under vacuum at 40-45 °C. Reaction mass was co-distilled with n- hexane (100 mL). Cool the reaction mass at 25-30 °C and charge n-hexane (200 mL). The isolated solid was filtered and wash with n-hexane (50 mL) and dried in vacuum oven at 35-40 °C to a constant weight, yielding 93.3 grams (95.2 %) of 3-ethoxy-4-hydroxybenzonitrile as light yellow solid.lH NMR (DMSO-d6) δ: 1.34 (t, 3H), 4.08 (q, 2H), 6.92 (d, 1H), 7.25 (m, 1H), 7.31 (s, 1H), 10.17 (s, 1H) ppm;FT IR (KBr): 617, 1026, 1287, 1518, 1599, 2225, 3228, 3378 cm"1;MS (ESI) m/z= 164.10 (M+ 1 ). |
91% | With trifluorormethanesulfonic acid; trimethylsilylazide In acetonitrile at 20℃; for 1.25h; Sealed tube; Inert atmosphere; | 3.3. General Procedure A for the Synthesis of Aromatic Nitriles General procedure: To a solution of an aromatic aldehyde 1 (0.500 mmol, 1.0 equiv) and TMSN3 (115 mg, 1.00 mmol,2.0 equiv) in a premixed HFIP/ACN mixture (2.0 mL, 1:1) in a nitrogen-flushed two dram vial wasadded triflic acid (TfOH; 17.7 L, 0.200 mmol, 0.40 equiv) (exotherm and brisk effervescence due tonitrogen gas evolution was immediately observed). The vial was capped and the reaction mixture wasallowed to stir at rt for 20-75 min. The reaction mixture was concentrated under nitrogen. The residueobtained was suspended in CH2Cl2/hexanes mixture and loaded on a silica gel in a 5 g samplecartridge. Purification using a normal phase silica flash column on a CombiFlash purification systemafforded a corresponding aromatic nitrile 2 upon concentration of appropriate fractions. |
85% | With hydroxylamine hydrochloride In acetonitrile Reflux; | Synthesis of 3-ethoxy-4-hydroxybenzonitrile used in the synthesis of Table 1 Molecule Number 31, 32, 34, 35, 36 & 37 Synthesis of 3-ethoxy-4-hydroxybenzonitrile used in the synthesis of Table 1 Molecule Number 31, 32, 34, 35, 36 & 37 _:A solution of ethyl vanillin (1 eq., 18 mmol) and hydroxylamine hydrochloride (1.2 eq.) in acetonitrile (1 M) was stirred for lh30 at reflux temperature. The reaction was quenched with water and extracted with diethyl ether. The organic layers were washed with a saturated aqueous NaHCC>3 solution, dried over MgS04and concentrated under reduced pressure. Recrystallization from di-i'so-propyl ether delivered the pure nitrile as white crystals (85% yield). |
With hydroxylamine hydrochloride; titanium(IV) oxide for 0.0833333h; Microwave irradiation; Neat (no solvent); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With zirconia nanopartices incorporated in multi-walled carbon nanotube nanocomposite In ethanol at 20℃; Green chemistry; | |
91% | With N-sulfonated biguanidine modified silica coated on cobalt ferrite nanoparticle core In ethanol at 20℃; for 0.25h; Green chemistry; | 2.2. General method for synthesis of 2-substituted benzimidazolederivatives General procedure: To a equimolar mixture of o-phenylenediamine (1.0 mmol), benzaldehyde(1.0 mmol) in 3 mL of ethanol, 20 mg of nanocatalyst(CFNPSO3H) was added and the reaction solution was subjected tocontinuous magnetic stirring at room temperature. The reaction progresswas closely monitored using TLC and after the verification of completion of reaction, the catalyst was removed from reaction mixtureusing an external magnet. After this, ice cold water was added to thereaction mixture leading to the formation of a precipitate. The crudeproduct in form of precipitate formed was filtered off and dried. Thecrude product was then recrystallized using ethanol to afford the pureproduct. |
85% | With 2,6-dimethyl-1-nitropyridin-1-ium trinitromethanide In neat (no solvent) at 20℃; for 0.5h; Green chemistry; |
75% | With sodium hydrogencarbonate In N,N-dimethyl-formamide at 80℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With caesium carbonate In acetone at 20℃; Cooling with ice; | 3.1 Step 1. 3-Ethoxy-4-(methoxy-d3)-benzaldehyde (10c). A mixture of commercially available 16a (5 g, 30 mmol) and Cs2CO3 (15 g, 46 mmol) in acetone was cooled in an ice-water bath. (CD3)2SO4 (99 atom % D, Cambridge Isotopes; 2.7 mL, 30 mmol) was added and the reaction was allowed to warm slowly to room temperature and was stirred overnight. The mixture was filtered through a pad of Celite and concentrated to give 5.7 g (approx 100%) of 10c. |
100% | With caesium carbonate In [(2)H6]acetone at 0 - 20℃; | 27 Preparation of 3-ethoxy-4-(d3-methoxy)-benzaldehyde The first batch was 10 g scale (based on (CD3)2SO4) and provided 13.9 g of product, area % 99.7%; and the second batch was 20 g scale and provided 28 g of product, area % 99.9%. The yields for both batches were quantitative. A mixture of 3-ethoxy-4-hydroxybenzaldehyde (12.6 g, 76 mmol) and Cs2CO3 (24.7 g, 75.9 mmol) in acetone was cooled in ice-water bath. (CD3)2SO4 (10.0 g, 75.9 mmol) was added and the reaction was allowed to warm slowly to room temperature and was stirred overnight. The reaction mixture was filtered through a pad of celite, the filtrate was concentrated to dryness to give a colorless liquid. The liquid was cooled to room temperature, forming a blue solid. The solid was dried under vacuum at 40° C. providing 13.9 g of the product, in 100% yield; 1H NMR (d6-DMSO) δ 1.35 (t, J=7.0 Hz, 3H), 4.09 (q, J=6.9 Hz, 2H), 7.17 (d, J=8.3 Hz, 1H), 7.37 (d, J=1.7 Hz, 1H), 7.55 (dd, J=1.9, 8.1 Hz, 1H), 9.83 (s, 1H). |
100% | With caesium carbonate In acetone at 20℃; Cooling with ice; | 3.1 3-ethoxy-4-(methoxy-d3)benzaldehyde The compound 16a (5 g, 30 mmol) was mixed with Cs2CO3 (15 g, 46 mmol) in acetone in an ice-mixture. (CD3) 2SO4 (99 at% D, Cambridge Isotopes; 2.7 mL, 30 mmol) was added,The reaction was allowed to warm slowly to room temperature and stirred overnight. The mixture was filtered through a pad of celite and concentrated to yield 5.7 g (ca. 100%) of compound 10c |
5.7 g | With caesium carbonate In acetone at 0 - 20℃; | 3.1 Step 1. 3-ethoxy-4-(methoxy-d3)benzaldehyde (10c) Commercially available 16a (5 g, 30 mmol) and Cs2CO3 (15 g, 46 mmol) in acetone were cooled in an ice bath. (CD3)2SO4 (99 atom% D, Cambridge Isotopes; 2.7 mL, 30 mmol) was added and the reaction was warmed slowly to room temperature and stirred overnight. The mixture was filtered through a pad of celite and concentrated to give 5.7 g (ca. 100%) of 10c. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With iodine; sodium hydrogencarbonate; potassium iodide In water at 20℃; | 5-Iodoethylvanillin (11b) To a solution of NaHCO3 (22.50 g, 0.27 mol) and KI (45.00 g, 0.27 mol) in water (900 mL) was added ethylvanillin (36.55 g, 0.22 mol) under rigorous stirring. Then, I2 (56.70 g, 0.22 mmol) was added in four portions in 30 min. The reaction mixture was stirred for 3 h at r.t., then was allowed to stand overnight. The crude product was collected by filtration, then washed with dilute Na2S2O3 solution and water to give compound 11b as a light brown powder, which was used without further purification. Yield: 61.68 g (96%); mp 129-130 °C; Rf = 0.68 (hexane-EtOAc, 1:1). 1H NMR (300 MHz, CDCl3): δ = 9.75 (s, 1H, CHO), 7.80 (s, 1H, 6-HAr), 7.35 (s, 1H, 2-HAr), 6.80 (br s, 1H, OH), 4.20 (q, J = 6.9 Hz, 2 H, OCH2CH3), 1.48 (t, J = 6.9 Hz, 3 H, OCH2CH3). 13C NMR (75 MHz, CDCl3): δ = 189.6 (CHO), 151.5 (4-CAr), 145.7 (3-CAr), 136.0 (6-CAr), 131.0 (1-CAr), 109.3 (2-CAr), 80.3 (5-CAr), 65.3 (OCH2CH3), 14.6 (OCH2CH3). |
94% | With N-chloro-succinimide; acetic acid; sodium iodide In N,N-dimethyl acetamide at 20℃; for 1h; | 148.i (i) 3-Ethoxy-4-hydroxy-5-iodobenzaldehyde General procedure: Ethylvanillin (2.0g, 12mmol) and sodium iodide (1.8g, 12mmol) were dissolved in acetic acid (8ml), and added dropwise with a solution of N-chlorosuccinimide (1.6g, 12mmol) in N,N-dimethylacetamide (10ml) at room temperature. After the reaction at room temperature for 1 hour, water (40ml) was added to the mixture, and the precipitated crystals were filtered to give the title compound (3.3g, yield94%). |
81% | With 2,2'-azinobis(3-ethylbenzthiazolinesulfonate); laccase; potassium iodide In dimethyl sulfoxide at 20℃; for 15h; Enzymatic reaction; |
76% | With sodium methylate; Iodine monochloride In dichloromethane at 0 - 20℃; for 3.5h; | 3-ethoxy-4-hydroxy-5-iodobenzaldehyde A-25 To a solution of ethylvanilline (1.35g ; 8.16 10-3 mol) at 0°C in dry dichloromethane, was added MeONa,(880mg ; 1.63 10-2 mol) and, slowly, a solution ofICl (2.64g ; 1.63 10-2 mol) in dry dichloromethane. After 30 min, the reaction mixture was allowed to warm up at rt and allowed to react for 3h at rt The reaction mixture was washed with a 0.5M solution of sodium thiosulfate and brine. The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to give a white solid recristalized in diethyl ether (1.80g ;76%). IR (ATR): 3272,2986, 2935, 2832, 2785, 2736, 1676, 1589, 1576 cm-1. 1H NMR(300 MHz, DMSO D6) δ ppm 10.51 (s, 1H), 9.74(s, 1H), 7.58 (s, 1H), 7.40 (s, 1H), 4.16 (q, J = 6.8 Hz, 2H), 1.38 (t, J= 6.8 Hz, 3H). 13C NMR(300 MHz, DMSO D6) δ ppm 190.2, 152.3, 146.3,134.4, 130.0, 111.0, 84.1, 64.5, 14.3. |
75% | With iodine; iodic acid In ethanol; water for 0.0833333h; Reflux; | |
With 2,2'-azinobis(3-ethylbenzthiazolinesulfonate); Trametes versicolor laccase; potassium iodide In aq. buffer at 20℃; for 20h; Enzymatic reaction; | 2 Demonstration of an antifungal effect of bio- iodinated vanillin and ethyl-vanillin on agar plates Experiments performed Vanillin and ethyl-vanillin (4 mM) were incubated in the presence of commercial T. versicolor laccase (250 mg per L) , 0.1 mM mediator ABTS and 50 mM potassium iodide in citrate-phosphate buffer (pH 5.0) for 20 h at room temperature. The reaction vessels with a liquid volume of 1 L were aerated with pressurized air through a frit. Reaction products were extracted by addition of 250 mL ethyl-acetate, thorough mixing and subsequent separation of the organic phase. The solvent was removed in a rotary evaporator at 50 °C under vacuum until solid products were obtained. Reaction products were re-dissolved in ethyl-acetate and analysed by HPLC-MS . Relative quantification of educts and products by integration of UV peak areas showed that the extracted substances consisted to 93% of iodo-vanillin and to 94% of iodo-ethyl- vanillin, respectively. | |
20.3 g | With tert-butylhypochlorite; sodium iodide In water; acetonitrile at 0℃; | 40.A A) 3-Ethoxy-4-hydroxy-5-iodobenzaldehyde [0515] After sodium iodide (19.84 g) was added to a mixture of 3-ethoxy-4-hydroxybenzadehyde (20.0 g), acetonitrile (300 mL) and water (60 mL), tert-butyl hypochlorite (14.9 mL) was added dropwise thereto at 0°C, and the resultant was stirred for 20 minutes at the same temperature. The reaction mixture was diluted by ethyl acetate and water, and the organic layer was separated. The obtained organic layer was washed with an aqueous saturated sodium thiosulfate solution and a saturated saline solution, dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was crystalized (acetonitrile/water), thereby obtaining the title compound (20.3 g). 1H MR (400 MHz, DMSO-ds) δ 1.38 (3H, t, J = 6.8 Hz), 4.16 (2H, q, J = 6.7 Hz), 7.40 (1H, s), 7.87 (1H, s), 9.74 (1H, s), 10.48 (1H, brs). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With nano-zirconia sulfuric acid In neat (no solvent) at 90℃; for 0.916667h; Green chemistry; | |
97% | With nano-γ-Fe2 O3 -SO3 at 60℃; for 0.0333333h; Microwave irradiation; | 4.1 method B 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. |
95% | With sulfonic acid immobilized on nano glass waste material In neat (no solvent) at 100℃; for 0.666667h; |
93% | In ethanol at 80℃; for 12h; | |
93% | With zirconia sulfuric acid In neat (no solvent) at 90℃; for 0.833333h; | 2.3 General Procedure for the Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones General procedure: A mixture of aromatic aldehyde (1 mmol), β-dicarbonyl compounds (1 mmol), and urea (or thiourea) (1.5 mmol) was stirred at 90 °C utilizing ZrSA (0.05 g, 15 wt%) for the appropriate time in solvent free condition until the reaction was complete. The reaction was monitored by thin layer chromatography (TLC) [7:3 hexane:ethyl acetate]. After the completion of the reaction the resulting mixture was cooled, eluted with hot ethanol (5 ml), centrifuged and filtrated to collect the formed precipitate. The crude product was recrystallized from ethanol to yield pure 3,4-dihydopyrimidin-2(1H)-ones derivatives. |
88% | With 40 wtpercent phosphotungstic acid supported on zirconia-encapsulated magnetite nanoparticles at 100℃; for 0.75h; Green chemistry; | 2.3.1 General Procedure fortheSynthesisof3,4-Dihydropyrimidin-2(1H)-ones 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 mol%) 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. |
85% | With iron(III) chloride hexahydrate; silica gel Microwave irradiation; | |
In ethanol Acidic conditions; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With natural dolomitic limestone In ethanol; water at 45 - 50℃; for 0.166667h; Sonication; Green chemistry; | General experimental procedure for the synthesis of the 2-aryl-1-arylmethyl-1Hbenzo[d]imidazoles 3 General procedure: A mixture of o-phenylenediamine (1, 1.0 mmol), the aromatic/heteroaromatic aldehyde 2 (2.0 mmol), and dolomitic limestone (5.0 wt %) was irradiated by ultrasound in a mixture of ethanol and H2O (1:1; 1.5 mL:1.5 mL) at 45-50 °C for 10-15 min. The progress of the reaction was monitored by TLC. After completion of the reaction, the reaction mass was allowed to cool to rt, and to it was added ethyl acetate (4.0 mL). Then, the catalyst was separated by filtration under vacuum and washed with ethyl acetate (1.0 mL). The filtrate was concentrated under reduced pressure to obtain the crude product 3. The formed crude solid 3 was further purified by recrystallization using hot aqueous ethanol (1.5 mL ethanol and 3.0 mL water). |
92% | With mesoporous mixed metal oxide nanocrystals of Al2O3-Fe2O3, Al2O3-V2O5, Al2O3-CuO at 109℃; for 0.0208333h; Neat (no solvent); Microwave irradiation; | |
90% | With zirconia nanopartices incorporated in multi-walled carbon nanotube nanocomposite In ethanol at 20℃; for 3h; Green chemistry; |
89% | In acetonitrile at 60℃; for 0.583333h; | General procedure: To a mixture of 1,2-phenylenediamine (0.54 g, 5 mmol) and aromatic/aliphatic aldehyde (10 mmol), catalytic amount (0.0108 g, 5 wt % of 1,2-phenylenediamine) of Al2O3-Fe2O3 nanocrystals was added using 5 mL of acetonitrile as solvent at room temperature under stirring. The reaction progress was monitored by TLC. After stirring for 10-45 min, under heating condition at 60 °C, the reaction mixture was cooled to room temperature and it was dissolved in ethanol (20 mL) and then poured into ice-water (40 mL). Ethyl acetate (50 mL) was added and the catalyst was separated out by filtration from the extraction mixture. The organic extract was dried over anhydrous sodium sulfate and excess of solvent was removed under reduced pressure so as to obtain the product. It was then purified by column chromatography over silica gel using hexanes/EtOAc as the eluting solvent system, yielding the pure products. An identical procedure for the synthesis of 2-substituted benzothiazoles was employed using 2-aminothiophenol (0.53 mL, 5 mmol) and aromatic/aliphatic aldehyde (5 mmol) in the presence of catalytic amount (5 wt % of 2-aminothiophenol) of Al2O3-Fe2O3 nanocrystals under heating condition (60 °C). |
84% | With Citrus limonium extract In ethanol at 80℃; for 0.75h; Green chemistry; | 3.1. General Procedure for the Synthesis of 2-aryl-1-arylmethyl-1H-benzimidazoles 4(a-s) General procedure: To the reaction mixture containing o-phenylenediamine(1 mmol) 1, aromatic aldehyde (2 mmol) 2, freshly preparedCLE (3 mL) and ethanol (5 mL) was added. Then the reactionmixture was stirred at 80oC on preheated oil bath forappropriate time mentioned in Table 2. The progress of reactionwas monitored by TLC (n-hexane:ethyl acetate, 3:1).The crude product 4 obtained after cooling at room temperature were separated by filtration and washed with 10 mL ofcold water by twice to remove the catalyst and dried in vacuum.The pure product was obtained by recrystallizationfrom 96% ethyl alcohol and their identity was ascertained onthe basis of FT-IR, 1H NMR and 13C NMR spectroscopictechniques. The physical and spectroscopic data are in consistentwith the proposed structure and is in harmony withthe literature values. Similar procedure was applied for thesynthesis of 2, 4, 5-trisubstituted imidazole derivatives inwhich aromatic aldehydes, benzil and ammonium acetate wereemployed as a substrate in 1:1:2 proportion respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With Aspergillus oryzae lipase In ethanol at 55℃; for 4h; Enzymatic reaction; | |
86% | With bifunctional periodic mesoporous organosilica supported potassium carbonate In ethanol at 50℃; for 1.66667h; | General procedure for the hot filtration test in theKnoevenagel reaction General procedure: The hot filtration test was carried out in the reaction of benzalde-hyde (2 mmol) with ethyl cyanoacetate (2.2 mmol) in the presenceof 0.5 mol% of catalyst in EtOH at 50C. After about 50% of the reac-tion was progressed, the obtained mixture was hotly filtered. Thefiltrate was then allowed to continue under optimized conditionsduring 3 h and the reaction progress was monitored |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.4% | With piperidine; acetic acid In toluene at 80℃; Dean-Stark; | 46.1 Preparation of Reaction Intermediate First, Compounds 46a to 60a (5-(3-ethoxy-4-hy- droxybenzylidene)-thiazolidine-2,4-dione), which are reactants used for synthesizing Compounds 46 to 60, were synthesized according to the following scheme.1 g (6.02 mmol) of 3-ethoxy-4-hydroxybenzalde- hyde and 0.705 g (6.02 mmol) of 2,4-thiazolidinedione were placed in a round flask equipped with a Dean-Stark trap, and then dissolved in 20 ml of toluene, which is a reaction solvent, and then, 0.297 ml (3.00 mmol) of piperidine and 0.172 ml (3.00 mmol) of acetic acid were added thereto, followed by the reaction at a temperature of 80° C. for 18 hours or more. The completion of the reaction was confirmed by TLC, and the resulting precipitate was recrystallized and then filtered under reduced pressure to obtain a pure solid.Yield: 90.4%1H NMR (300 MHz, DMSO-d6) 0 12.46 (s, 1H),0 9.88 (s, 1H), 0 7.69 (s, 1H), 0 7.15 (d, J=1.83 Hz, 1H), 07.07 (dd, J=8.43 and 1.83 Hz, 1H), 0 6.94 (d, J=8.43 Hz, 1H), 0 4.10 (m, J=6.96 Hz, 2H), 0 1.37 (t, J=6.96 Hz, 3H) |
29% | With piperidine In ethanol for 24h; Inert atmosphere; Reflux; | 5.2.1. General procedure for the synthesis of substituted benzylidene-thiazolidine-2,4-dione analogs (2a-2l) General procedure: Piperidine (0.3 eq.) was added to a suspension of substituted benzaldehydes (approximately 1.44-2.60 mmol) and thiazolidine-2,4-dione (approximately 0.7-1.2 eq.) in EtOH (4 mL), and the reaction mixture was refluxed. Before reaching the boiling point of ethanol, the reaction mixture generally became a clear solution. During reflux, precipitates were formed and filtered through a Buchner funnel after cooling. The filter cake was washed with ethanol, methylene chloride, and/or water, depending on the properties of the substituted benzaldehydes used for the reaction, to obtain products (yields: approximately 20.4%-79.2%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 3.5h; | Reference Example 12 4-[2,4-bis(trifluoromethyl)benzyl]oxy}-3-ethoxybenzaldehyde; [Show Image] To a solution (3.1 mL) of 3-ethoxy-4-hydroxybenzaldehyde (513.5 mg) and potassium carbonate (512.5 mg) in DMF was added <strong>[140690-56-8]1-(bromomethyl)-2,4-bis(trifluoromethyl)benzene</strong> (0.64 mL), and the mixture was stirred at room temperature for 3.5 hr. Water was added to the reaction mixture, and the precipitate was collected by filtration to give the title compound as a colorless powder (yield: 1.19 g, 98%). 1H-NMR (CDCl3, 300 MHz):delta1.50 (3H, t, J = 7.0 Hz), 4.20 (2H, q, J = 7.0 Hz), 5.46 (2H, s), 6.96 (1H, d, J = 8.1 Hz), 7.41 (1H, dd, J = 8.1, 1.9 Hz), 7.46 (1H, d, J = 1.9 Hz), 7.86 (1H, d, J = 8.3 Hz), 7.95 (1H, s), 8.02 (1H, d, J = 8.3 Hz), 9.86 (1H, s) . |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With ammonium acetate In neat (no solvent) at 100℃; for 0.333333h; | General procedure for the synthesis of 2,4,5-trisubstituted imidazoles General procedure: (1.0 mmol), ammonium acetate (2.0 mmol), benzil(1.0 mmol), and n-Fe3O4/PVAm-SO3H nanocomposite(0.015 g) as catalyst was taken to a round-bottom flask witha magnetic stirrer and placed in an oil bath to keep the temperatureat 100 °C for the period of time (the reaction wasmonitored by TLC) as indicated in Table 2. After completionof the reaction, the reaction mixture was dissolved inethanol (5 mL) and the catalyst was separated by an externalmagnet. After the reaction mixture was concentrated under rotary vacuum evaporation, the obtained solid product waswashed with water and recrystallized from ethanol to offerthe pure product. The products were known and characterizedby melting points, 1H NMR, and FT-IR spectroscopytechniques |
94% | With ammonium acetate In neat (no solvent) at 90℃; | General procedure for the synthesis of 2,4,5-trisubstituted imidazoles General procedure: To a well-stirred mixture of aromatic aldehyde (1.0 mmol), ben-zil (1.0 mmol), ammonium acetate (2.5 mmol) and PeSA (0.03 g,15 mol%) as catalyst was reacted in an oil bath at 90C withoutsolvent for the appropriate time. After completion of the reaction,the solid materials residue was then washed with acetone, desiredinsoluble catalyst was collected by filtration and the solvent wasevaporated to give the crude product. For further purification itwas crystallized from ethanol to afford pure imidazole derivatives. |
94% | With ammonium acetate In neat (no solvent) at 100℃; for 1.33333h; Green chemistry; |
94% | With ammonium acetate In neat (no solvent) at 100℃; for 0.833333h; Green chemistry; | |
90% | With copper(II) ferrite; ammonium acetate In neat (no solvent) at 90℃; for 0.733333h; Green chemistry; | |
88% | With ammonium acetate In ethanol for 1.5h; Reflux; | |
88% | With vanadatesulfuric acid; ammonium acetate at 80℃; for 0.916667h; | General procedure for the preparation of multisubstituted imidazoles General procedure: In a round-bottom flask, the aldehyde (1 mmol), benzil or benzoin (1 mmol), ammonium acetate (2 mmol for 2,4,5-trisubstituted imidazoles and 1 mmol for 1,2,4,5-tetrasubstituted imidazoles) or aniline (1 mmol for 1,2,4,5-tetrasubstituted imidazoles) and VSA (10 mol %) were mixed thoroughly. The flask was heated at 80°C under continuous stirring. After the its completion, the reaction as monitored by TLC (eluent/EtOAc/hexane = 1 : 4 vol.), acetone (10 mL) was added and the solid catalyst was then filtered and separated. The solvent was evaporated and the crude products were purified by column chromatography or recrystallization from ethanol (Tables 2 and 3). Then, the products were characterized by IR, 1H NMR, 13CNMR and also the comparison of their melting points with those reported in literature. |
87% | With citrate trisulfonic acid; ammonium acetate In neat (no solvent) at 90℃; for 0.666667h; | |
78% | With 2-Picolinic acid; ammonium acetate In neat (no solvent) at 120℃; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 2h; | Synthesis of 21 Chloromethyl methyl ether (10 mmol, 2 equiv.)was added to a stirred solution of 3-ethoxy-4-hydroxybenzaldehyde (5 mmol, 1equiv.) in CHCl2 (10 mmol, 2 equiv.) and DIPEA (10 mmol, 2 equiv.)at 0 to RT for 2 hours. Then the reaction mixture was washed with water andthe solvent was removed in vacuo to obtain 3-ethoxy-4-(methoxymethoxy)benzaldehyde(19, 900 mg, 85%): 1H NMR(400 MHz, CDCl3): δ 9.81(1H, s), 7.37 (1H, s), 7.35 (1H, d, J= 8.4), 7.22 (1H, d, J = 8.4), 5.26(2H, s), 4.11 (2H, q, 7.0), 3.48 (3H, s), 1.43 (3H, t, 6.8). 19 reacted with sophoridine using sameprocedure described in synthesis of 11-16 to obtain 14-(3-ethoxy-4-(methoxymethoxy)phenylmethylene)sophoridine (21, 100 mg, 28%) |
83.6% | Stage #1: 4-hydroxy-3-ethoxybenzaldehyde With sodium hydride In N,N-dimethyl-formamide at 0℃; Stage #2: chloromethyl methyl ether In N,N-dimethyl-formamide at 0 - 20℃; for 2h; | 5.1.4. General procedure B for the synthesis of 37b-42b General procedure: To a solution of hydroxyl substituted aromatic aldehydes (1.0 mmol) in anhydrous DMF (10 mL) at 0 °C was added NaH (2.0 mmol, 60%). Then methyl chloromethyl ether (2.0 mmol) was added dropwise to the mixture. The ice bath was removed and stirred at room temperature for 2 h. The reaction mixture was quenched with water, extracted with ethyl acetate and purified by silica gel column chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With ammonium cerium (IV) nitrate In isopropanol at 50℃; Irradiation; | General procedure for the preparation of 3a-l: General procedure: To a solution of 5,5-dimethyl-1,3-cyclohexanedione (1, 2 mmol) and aldehyde (2, 1 mmol) in 2-propanol (2 mL) was added ceric ammonium nitrate (5 mol %) and the mixture was irradiated in a water bath of ultrasound (40 kHz) continuously at 50 °C till the completion of the reaction (monitored by TLC). The temperature of the water bath was maintained at 50 °C by adding additional cold water whenever necessary and was examined by using a thermometer at a regular interval. After completion of the reaction the mixture was filtered and the residue was washed with 2-propanol (2 × 2 mL). The filtrates were collected, combined, and concentrated. The residue was purified by recrystallization from EtOH to give the desired products (3). All the products prepared (3a-m) were known compounds and characterized by NMR, IR, and MS spectra. The data generated were compared with that reported in the literature. |
90% | With boron trifluoride diethyl ether complex In ethanol Reflux; | General procedure for the synthesis of xanthenes (5, 6 and 7) General procedure: A mixture of hydroxy benzaldehydes (1 mmol) and 5,5-dimethylcylcohexane-1,3-dione (2 mmol) was refluxed in ethanol with BF3/OEt2 as catalyst for 3-4 h. After the completion of the reaction (monitored by TLC), the resulting precipitate was filtered, washed with water and a small amount of ice cold ethanol. The crude product was recrystallized from absolute ethanol and it was found to be pure and no further purification was necessary. |
86% | With Orthoboric acid In ethanol; lithium hydroxide monohydrate at 26℃; for 0.916667h; Sonication; | 3.1. General procedure for synthesis of xanthendiones General procedure: A mixture of various aromatic aldehydes (1 mmol), dimedone (2 mmol), and catalytic amount of boric acid was added in a round bottom flask with a 1:1 mixture of ethanol-water solvent system and placed in a sonic bath and sonicated at room temperature un- til the reaction was complete Scheme 1 . Reactions were monitored by thin-layer chromatography (TLC) and after completion of the re- action, the mixture was cooled to room temperature and filtered. The precipitate obtained was washed with water. The crude product was further recrystallized using ethanol as the solvent. |
86% | With Orthoboric acid In ethanol; lithium hydroxide monohydrate at 28℃; for 1h; Sonication; | 2.2. General procedure for synthesis of 3(a-b) General procedure: A mixture of substituted benzaldehyde (1 mmol), dimedone (2 mmol), and 4.5% equivalentof boric acid as catalyst were taken in a round bottom flask and a 1:1 mixture ofwater-ethanol was added to it and sonicated at room temperature until the reaction wascomplete (Scheme 1). The reaction was monitored by thin-layer chromatography (TLC),and after completion of the reaction, the mixture was cooled to room temperature andfiltered. The product was recrystallisation from DMF solvent that yielded single crystals. |
With boron trifluoride diethyl ether complex In ethanol for 3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With silica coated magnetic nanoparticles with ionic liquid tags at 80℃; for 0.25h; | |
94% | With iron oxide; ammonium acetate at 60℃; for 0.2h; | General procedure for the preparation of polyhydroquinolines General procedure: In a round-bottomed flask the aldehyde (1 mmol), 1,3-cyclohexanedione derivatives (1 mmol), ammonium acetate(1.5 mmol), β-ketoester (1 mmol) and Fe3O4NPs (0.016 g, equal to7 mol%) were mixed thoroughly. The flask was heated at 60C with concomitant stirring. After completion of the reaction confirmed by TLC (eluent: EtOAc:n-hexane), hot ethanol (10 mL) was addedand separated solid catalyst by a normal magnet. The solvent was evaporated and the crude products were recrystallized from ethanol, gave the pure products in 84-96% yields based on the starting aldehyde. The products were characterized by IR,1H NMR,13C NMR and via comparison of their melting points with the reported ones. Spectroscopic data of new compounds. |
92% | With ammonium acetate In neat (no solvent) at 100℃; for 1.25h; Green chemistry; |
91% | With ammonium acetate In neat (no solvent) at 80 - 85℃; for 0.333333h; Green chemistry; | |
91% | With ammonium acetate; N-sulfonic acid pyridinium chloride In neat (no solvent) at 110℃; for 0.583333h; Ionic liquid; | General procedure for the synthesis of Hantzsch polyhydroquinolines (5a-m) General procedure: Ionic liquid, [pyridine-SO3H]Cl (10 mol%, 0.1 mmol, 19.56 mg) was added to a mixture of dimedone (1 mmol, 140.18 mg), aldehyde (1 mmol), ethyl acetoacetate (1 mmol, 127.46 lL), and ammonium acetate (3 mmol, 231.25 mg), and heated at 110 C under neat conditions for an appropriate time, as described in Table 1. After completion of the reaction shown by TLC, the mixture was diluted with water and the product was extracted with ethyl acetate (3 9 10 mL). The combined organic layer was dried over Na2SO4 and concentrated under reduced pressure, and then purified by recrystallization from ethanol to obtain the pure polyhydroquinoline derivatives. The recovered catalyst was washed with ethyl acetate, dried under vacuum at 90 C for about 2.5 h, and reused for consecutive reactions. |
90% | With iron(III) oxide; ammonium acetate In neat (no solvent) at 50℃; for 6h; | |
88% | With ammonium acetate In neat (no solvent) at 80℃; for 0.5h; Green chemistry; | 2.7. General procedure for the synthesis of polyhydroquinolinederivatives via Hantzsch reaction General procedure: To a test tube containing a mixture of aromatic aldehydes(1 mmol), dimedone (1 mmol, 0.14 g), ethyl (or methyl) acetoacetate (1 mmol) and ammonium acetate (1.5 mmol, 0.11 g) wasadded Cu(II)-PAA/M-MCM-41 (0.02 g) as a catalyst. Then, the reactionmixture was stirred at 80 °C under solvent-free conditions.The progress of the reactions was monitored by TLC (ethyl acetate/n-hexane, 1:4). After the completion of the reaction, the resultingmixture was cooled to room temperature and then cold waterwas added. The obtained solid was collected by filtration and purifiedby recrystallization from hot ethanol to afford the pure product.In this study, the catalyst was recycled and reused five timeswithout significant loss of its catalytic activity. |
78% | With ammonium acetate In neat (no solvent) at 80℃; for 0.25h; | General procedure for synthesis of desired molecules 1a-l General procedure: To a mixture of arylaldehyde derivatives (1 mmol), dimedone (1 mmol, 0.140 g), ethyl acetoacetate (1 mmol, 0.130 g), and ammonium acetate (1.5 mmol, 0.115 g) in around-bottomed flask, 10 mg of novel nanomagnetic catalyst was added. The obtained mixture was stirred at 80 °C for proper time as indicated in Table 2 under solvent-free condition. Reaction progress was monitored by TLC using a mixture of EtOAc and n-hexane as eluent. After reaction completion, to separate the catalyst, hot EtOH was added to the reaction mixture to dissolve the product and unreacted starting materials. After catalyst separation using an external magnet, pure product was obtained after recrystallization from EtOH in good to high yield as indicated in Table 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30.1% | With acetic acid; 2-Methylpiperidin In toluene at 130℃; for 2h; Inert atmosphere; | 5.1.2 General procedure for synthesis of 3,4-dihalo-5-(4-hydroxybenzylidene)furan- 2(5H)-one intermediates (A1B1) General procedure: Benzaldehyde derivatives (B1, 1.0mmol) and halogenated furanones (A1, 1.0mmol) were dissolved in anhydrous toluene (30mL), and then a catalytic amount of 2-methyl piperidine and glacial acetic acid were slowly dropped to the solution under the atmosphere of nitrogen. The reaction mixture was refluxed at 130°C for 2h until the disappearance of starting materials (TLC analysis), and then cooled to room temperature. The toluene was removed under reduced pressure and the residue was dissolved in methanol. This solution was concentrated and purified by silica gel column chromatography with ethyl acetate-petroleum (1:12) as eluent to produce resultant intermediates. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With nano-γ-Fe2 O3 -SO3 at 60℃; for 0.036h; Microwave irradiation; | 4.1 method B 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 nano-zirconia sulfuric acid In neat (no solvent) at 90℃; for 0.666667h; Green chemistry; | |
93% | With sulfonic acid immobilized on nano glass waste material In neat (no solvent) at 100℃; for 0.666667h; |
86% | With 40 wtpercent phosphotungstic acid supported on zirconia-encapsulated magnetite nanoparticles at 100℃; for 0.75h; Green chemistry; | 2.3.1 General Procedure fortheSynthesisof3,4-Dihydropyrimidin-2(1H)-ones 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 mol%) 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. |
85% | With polythiophene immobilized on Fe3O4 functionalized carbon nanotube In neat (no solvent) at 80℃; for 0.583333h; Green chemistry; | Preparation of dihydropyrimidinones and octahydroquinazolinones via Biginelli reaction General procedure: A mixture of benzaldehyde derivatives (1.0 mmol), β-keto ester or dimedone (1.0 mmol), urea or thiourea (1.5 mmol), and CNT-Fe3O4-PTh (30 mg) was stirred at 80 °C for an appropriate time (Table 2). Upon completion of the reaction, as screened by TLC, hot ethanol was added to dissolve the product completely and catalyst was separated using a permanent magnet. The solvent was evaporated to dryness, and residue was crystallized in ethanol. |
81% | With zirconia sulfuric acid In neat (no solvent) at 90℃; for 1h; | 2.3 General Procedure for the Synthesis of 3,4-Dihydropyrimidin-2(1H)-ones General procedure: A mixture of aromatic aldehyde (1 mmol), β-dicarbonyl compounds (1 mmol), and urea (or thiourea) (1.5 mmol) was stirred at 90 °C utilizing ZrSA (0.05 g, 15 wt%) for the appropriate time in solvent free condition until the reaction was complete. The reaction was monitored by thin layer chromatography (TLC) [7:3 hexane:ethyl acetate]. After the completion of the reaction the resulting mixture was cooled, eluted with hot ethanol (5 ml), centrifuged and filtrated to collect the formed precipitate. The crude product was recrystallized from ethanol to yield pure 3,4-dihydopyrimidin-2(1H)-ones derivatives. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62.4% | With sodium acetate; acetic acid; for 3h;Reflux; | General procedure: [0220] In an acetic acid (4 ml/sodium acetate 1 g) solvent, a mixture including a substituted benzaldhehyde (300 mg, mmol), <strong>[60-27-5]creatinine</strong> (1.1 eq.), and sodium acetate (NaOAc)(3 .0 eq.) was refluxed for 2 to 4 hours. After cooling, water was added thereto, and the reaction flask was maintained at a temperature of 0 C. The produced precipitate was filtered, and in consideration ofphysical characteristics of the residual starting material, the resultant product was washed with iced water and/or methylene chloride to obtain a solid target compound. [0225] Orange solid; a reaction time of 3 hours; a yield of62.4%; a melting point of 254.2-255.6 C.; 1H NMR (400MHz, DMSO-d5) oe 9.14 (br s, 1H), 8.41 (s, 1H), 7.75 (br s,2H), 7.30 (d, 1H, J=8.0 Hz), 6.69 (d, 1H, J=8.4 Hz), 6.10 (s,1H), 4.01 (q, 2H, J=6.8 Hz), 3.11 (s, 3H), 1.32 (t, 3H, J=7.2Hz); 13C NMR (100 MHz, DMSO-d5) oe 175.3, 166.3, 147.8,146.5, 133.4, 126.3, 125.3, 115.9, 115.8, 115.6, 64.3, 28.5,15.4. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With triethylamine hydrobromide In water at 60℃; | 4.1. General procedure for the synthesis of compounds 1-18 General procedure: In synthesis of biscoumarin analogs 1-18 (Scheme 1), to a stirred mixture of coumarin derivatives (4.0 mmol) and substituted aromatic aldehyde (2.0 mmol) in water and 10 mol% triethylammonium bromide (TEAB) was added. The reaction mixture was stirred at 60 °C for 1-2 h. Completion of reaction was monitored by periodic TLC. After completion of reaction, it was filtered, and then washed with distilled water affording a pure product in high yields. In some cases pure products were obtained through column chromatography (silica gel) using 3:7 acetone and n-hexane as eluent. The structures of compounds 1-18 were deduced by using different spectroscopic techniques, including 1H NMR and EI mass spectroscopy. All synthetic compounds 1-18 gave satisfactory elemental analyses. |
With tetraethylammonium bromide In water at 60℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | With triethylamine hydrobromide In water at 60℃; | 4.1. General procedure for the synthesis of compounds 1-18 General procedure: In synthesis of biscoumarin analogs 1-18 (Scheme 1), to a stirred mixture of coumarin derivatives (4.0 mmol) and substituted aromatic aldehyde (2.0 mmol) in water and 10 mol% triethylammonium bromide (TEAB) was added. The reaction mixture was stirred at 60 °C for 1-2 h. Completion of reaction was monitored by periodic TLC. After completion of reaction, it was filtered, and then washed with distilled water affording a pure product in high yields. In some cases pure products were obtained through column chromatography (silica gel) using 3:7 acetone and n-hexane as eluent. The structures of compounds 1-18 were deduced by using different spectroscopic techniques, including 1H NMR and EI mass spectroscopy. All synthetic compounds 1-18 gave satisfactory elemental analyses. |
With tetraethylammonium bromide In water at 60℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With copper(II) choride dihydrate In ethanol for 16h; Reflux; | 12 General procedure for the synthesis of compounds 1-25 General procedure: In a typical procedure, 2-arylquinazolin-4(3H)-ones 1-25 were synthesized by mixing anthranilamide (2 mmol), substituted benzaldehydes (2.1 mmol) and CuCl2*2H2O (4 mmol) in ethanol (15 mL). The mixtures were refluxed for 16 h, while progress of the reaction was monitored through thin layer chromatography. After completion of reaction, the reaction mixtures were cooled to room temperature and distilled water was added until the formation of precipitates. The precipitates were filtered and washed with distilled water. This reaction afforded good yields of title compounds. 4.4.12 2-[3'-(Ethyloxy)-4'-hydroxyphenyl]quinazolin-4(3H)-one (12) Yield: 98%; 1H NMR: (400 MHz, DMSO-d6): δH 12.32 (s, 1H, NH), 9.67 (s, 1H, 4'-OH), 8.11 (d, 1H, J5,6 = 7.6 Hz, H-5), 7.77 (m, 3H, H-7, H-8, H-2'), 7.68 (d, 1H, J6',5' = 8.0 Hz, H-6'), 7.47 (t, 1H, J6(5,7) = 7.2 Hz, H-6), 6.91 (d, 1H, J5',6' = 8.4 Hz, H-5'), 4.16 (q, 2H, J(CH2,CH3) = 6.8 Hz, CH2), 1.39 (t, 3H, J(CH3,CH2) = 7.2 Hz, CH3); EI-MS: m/z (rel. abund.%), 282 (M+, 100), 267 (29.3), 254 (80.9), 238 (11.9), 119 (46.8). Anal. Calcd for C16H14N2O3: C, 68.07; H, 5.00; N, 9.92; O, 17.00. Found: C, 68.05; H, 5.04; N, 9.94. |
98% | With copper(II) choride dihydrate In ethanol for 16h; Reflux; | 4.6. General procedure for the synthesis of compounds 1-25 General procedure: 2-Aminobenzamide (1 eq.), substituted benzaldehydes (1.1 eq)and CuCl22H2O (4 eq.) were mixed in ethanol (15 mL) and refluxedfor 16 h. The reaction was periodically monitored by thin layerchromatography. Water was added to the reaction mixtures untilthe appearance of precipitates. These precipitates were filtered,washed with water, and dried under vacuum. Good yields of titlecompounds were obtained [33]. |
47% | In dimethyl sulfoxide at 100℃; | 2.2.3. Synthetic Procedure for the Preparation of 6-8 General procedure: Anthranilamide (1) (1.0 mmol, 0.136 g) was dissolved in DMSO (10 mL) and then corresponding aldehyde was added (1.2 mmol). The reaction mixture was stirred at 100 °C in an open flask for 16-20 h and cooled to room temperature. After the addition of water (50 mL), precipitate was formed and collected by filtration. If needed, quinazolinones were recrystallized from ethanol. |
With copper(II) choride dihydrate In ethanol for 16h; Reflux; | ||
With copper(II) chloride dihydrate In ethanol for 16h; Reflux; | 2.1. Chemical Synthesis General procedure: Twenty-five 2-aryl quinazoline-4(3H)-one derivative 1-25 were previously synthesized by reacting anthranilamidewith various benzaldehydes. CuCl2·2H2O in ethanol wasused as a catalyst. The reaction proceeded under reflux for16 h. The structure elucidation of each compound wascarried out by 1H NMR and EI mass spectrometry. Scheme 1represents the general scheme of synthesis of compounds1-25 [13]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: 4-hydroxy-3-ethoxybenzaldehyde In dichloromethane for 0.5h; Stage #2: pivaloyl chloride With triethylamine In dichloromethane at 20℃; for 2h; | General procedure: The corresponding phenol (3 mmol) was dissolved in dichloromethane (5 mL) and4-dimethylamiopyridine (0.1 mmol) was added. The reaction was stirred for 0.5 h before addition ofpivaloyl chloride (6 mmol) followed by dropwise addition of triethylamine (6 mmol). The reactionmixture was stirred at room temperature for 2 h. The reaction solution was poured intodichloromethane (100 mL) and washed with saturated sodium chloride solution (2 × 100 mL) andsaturated sodium bicarbonate solution (2 × 100 mL). The organic phase was collected, dried overanhydrous magnesium sulfate, and filtered, and then the solvent was removed in vacuo to obtaincompounds 10-12. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.36% | With ammonium cerium (IV) nitrate; ammonium acetate; In ethanol;Reflux; | General procedure: A mixture of benzil (0.01 mol), aldehydes (0.01 mol), <strong>[3641-13-2]3-amino-1,2,4-triazole-5-carboxylic acid</strong> (0.01 mol), ammonium acetate (0.01 mol) and ceric ammonium nitrate (15 mol%) as a catalyst were refluxed in ethanol (15 mL) for about 3-4 h. The progress of the reaction was monitored by TLC. After completion of reaction, the mixture was cooled to room temperature. The solid formed was filtered and dried. The crude products were recrystallized by ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With 1-methylimidazolium trinitromethanide In neat (no solvent) at 25℃; for 0.333333h; Inert atmosphere; Green chemistry; | |
90% | With dioxomolybdenum azo azomethine complex supported on silica coated magnetite nanoparticles In neat (no solvent) at 20℃; for 0.333333h; | |
90% | With potassium phtalimide In ethanol; water at 50℃; for 10h; Green chemistry; | General Procedure for the synthesis of 5-aminopyrazole-4-carbonitrile derivatives (4a-s) catalyzedby PPI General procedure: The appropriate aldehyde (1 mmol), phenylhydrazine (2, 1 mmol), malononitrile (3, 1 mmol), and PPI as a catalyst (15 mol%) was mixed in a mixture of EtOH:H2O (2:1). Then, the reaction mixture was heated at 50 °C for the appropriate time (Table 2). After completion of the reaction as indicated by TLC analysis, the reaction mixture was cooled to room temperature and poured into water. The precipitated products were filtered off, washed with ice water and dried at room temperature. The crude products(except 4i and 4n) were purified by recrystallization from EtOH. The filtrate containing the catalyst wasused as such for exploring the reusability of the catalyst. The catalyst is soluble in water while the products are insoluble in water. Spectral data for 4a and 4j were as follows: |
90% | With zirconia nanopartices incorporated in multi-walled carbon nanotube nanocomposite In water at 20℃; for 2h; Green chemistry; | |
60% | Stage #1: 4-hydroxy-3-ethoxybenzaldehyde; malononitrile With 4-carboxy-1-sulfopyridin-1-ium monozinc(II) trichloride In neat (no solvent) at 80℃; for 0.0833333h; Stage #2: phenylhydrazine In neat (no solvent) at 80℃; for 0.666667h; | General procedure for the synthesis of 5-amino-1H-pyrazole-4-carbonitriles General procedure: A mixture of aromatic aldehyde, (1 mmol), malononitrile (1 mmol, 0.066 g) and [4CSPy]ZnCl3 (1.875 g, 5 mol %) as a catalyst was added to 25-mL round-bottomed flask connected to a reflux condenser and heated at 80 °C for 5 min. Then, phenylhydrazine (1 mmol, 0.108 g) was added to the reaction mixture and stirred at 80 °C for appropriate time under solvent-free condition. After the completion of the reaction, as monitored by TLC, the reaction mixture was extracted with warm ethyl acetate (10 mL) and separated from the catalyst by simple filtration. Finally, the desired product was purified by the recrystallization in ethanol (90%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With pyrazine-1,4-diium trinitromethanide In neat (no solvent) at 25℃; for 0.416667h; Green chemistry; | General procedure for the synthesis of 1-(α-aminoalkyl)-2-naphthol derivatives as a novel Betti bases General procedure: To a mixture of aromatic aldehydes (1 mmol), β-naphthol (1 mmol; 0.144 g) and 2 or 4-aminopyridine (1 mmol; 0.094 g) in a round bottom flask, 1 mol% of [1,4-DHPyrazine][C(NO2)3]2} nano-structured molten salt or 2 mol% of Ag-TiO2 nano composite was added as catalyst and stirred at room temperature under solvent-free conditions for appropriate time (Table 4). After completion of the reaction as monitored by thin layer chromathography (TLC) (n-hexane/ethyl acetate: 5/2), ethyl acetate (10 mL) was added to reaction mixture and stirred under reflux condition for 10 min. Then, the resulting mixture was washed with water (10 mL) and decanted to separate catalyst from the other materials (the reaction mixture was soluble in hot ethyl acetate and nano molten salt catalyst was soluble in water). The aqueous layer was decanted, separated and removed the water to give the catalyst for another reaction. The solvent of organic layer was removed and the crude product was purified by recrystallization from ethanol (95%). Note: In another procedure, for the recycle of Ag-TiO2 nano composite, at the end of reaction, warm ethyl acetate was added to the reaction mixture and centrifuged to separate product and starting materials from the catalyst (Ag-TiO2 nano composite as catalyst is insoluble in ethyl acetate). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With thionyl chloride In methanol | |
70% | With thionyl chloride In methanol at 20℃; | Synthesis of Indolyl Chalcones 2(a-k) General procedure: To a solution of 3-acetylindole 6 (1 mmol) and appropriate aldehyde 7 (1 mmol) in methanol (20 mL) was added SOCl2 (2 mL) and stirred the reaction mixture for 2 h. The contents of reaction mixture were poured into ice-cold water. The solid so obtained was filtered, dried and recrystallized from ethanol to afford pure 2(a-k) viz, Trans-1-indolyl-3-(3',4’,5’-trimethoxyphenyl)-2-propen-1-one (2a), Trans-1-indolyl-3-(3'-ethoxy-4-hydroxyphenyl)-2-propen-1-one (2b), Trans-1-indolyl-3-(benzodioxanyl)-2-propen-1-one (2c), Trans-1-indolyl-3-(4'-hydroxyphenyl)-2-propen-1-one (2d), Trans-1-indolyl-3-(anthracenyl)-2-propen-1-one (2e), Trans-1-indolyl-3-(2',4’-dimethoxyphenyl)-2-propen-1-one (2f), Trans-1-indolyl-3-(2'3',4’-trimethoxyphenyl)-2-propen-1-one(2g), Trans-1-indolyl-3-(3',5’-dimethoxy-4’-hydroxyphenyl)-2-propen-1-one (2h), Trans-1-indolyl-3-(3',5’-dimethoxy-4’-benzyloxyphenyl)-2-propen-1-one (2i), Trans-1-indolyl-3-(thiophenyl)-2-propen-1-one (2j), Trans-1-indolyl-3-(2'-methylphenyl)-2-propen-1-one (2k). Spectral data of the compounds 2(a-k) was compared with the reported data in the literature by Gaur et al 2015. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With piperidine; acetic acid; In toluene; at 80.0℃;Dean-Stark; | Thiazolidine-2,4-dione 1g (0.008538 mol), 3-Ethoxy-4-hydroxy-benzaldehyde 1.419g, Piperidine 0.422ml, Acetic acid (0.182 ml) and toluene (20 ml) in a dean-stark apparatus at 80 C, After reacting for 12 hours or longer, it was recrystallized to obtain pure 5- (3-Ethoxy-4-hydroxy-benzylidene) -thiazolidine-2,4-dione. Yield: 90%. |
69% | With piperidine; In ethanol;Reflux; | General procedure: Equimolar mixture of substituted benzaldehyde (20 mM)and 2,4-thiazolidinedione (20 mM) with catalytic amount ofpiperidine (1.4 g, 16 mM) and ethanol (150 mL) was refluxedcontinuously for 30-35 hours. The reaction mixturewas poured into water and filtered. On cooling, the productwas precipitated out from ethanol [36]. This step was used tosynthesize a total of ten intermediates (FP1I-FP10I). |
With piperidine; acetic acid; In toluene; at 80.0℃; for 18h;Dean-Stark; | General procedure: 2,4-Thiazolidinedione 1.0 g (8.54 mmol) and 4-hydroxybenzaldehyde 1.0 g (1.0 equiv; 8.54 mmol) were dissolved in a 100-mL round flask containing 20 mL toluene. Piperidine 0.40 mL (0.5 equiv; 4.27 mmol) and 0.25 mLacetic acid (0.5 equiv; 4.27 mmol) were added slowly tothe reaction mixture and refluxed at 80 C for over 18 hwith dean-stark trap. The resulting solution was concentrated under reduced pressure to remove the solvent. The residual layer was washed with methanol and dried to afford compounds (a-e) as yellow solid. Synthesis ofcompounds a is shown in Scheme 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.4% | With acetic acid In ethanol at 60℃; for 1.5h; | 15 General method of synthesis of compounds (5a-j) General procedure: To a solution of the compound 2 (mLeq) in ethanol (10 mL), thecorresponding aromatic aldhyde or sugar aldhyde (mLeq) wasadded and 0.5 mL of acetic acid (33%). The reaction mixture washeated under reflux for 1.5 h and then left to cool to room temperature.The solid that separated out was filtered off, washed withethanol, and dried. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | for 0.15h;Microwave irradiation; | General procedure: Second step consists of condensation of <strong>[6761-52-0]3-aminopyrazine-2-carbohydrazide</strong> (0.5 gm, 0.003 mol) with aromatic aldehydes (0.5 gm, 0.008 mol) using microwaveirradiation (8 - 10 min, 350 W). After cooling and filtration,the product was recrystallized using ethanol [6, 9] (Fig. 1). |
In ethanol;Microwave irradiation; | General procedure: Asolution of aromatic/substituted aldehydes (0.008 mole, 0.9gm) in 25ml ethanolwas added to a solution of compound 2(0.003 mol, 0.5gm) in 10 ml ethanol and wasirradiated in a microwave oven for 8-10 min (350 W). The resultanthydrazone was precipitated by addition of water (30 ml). The product wasfiltered and purified using ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With 1-methylimidazolium tricyanomethanide In neat (no solvent) at 20℃; for 0.166667h; Green chemistry; | 2.2. General procedure for the synthesis of tetrahydrobenzo[b]pyransderivatives General procedure: [HMIM]C(CN)3} as a nano structuremolten salt catalyst (0.5 mol%)was added to a mixture of several aromatic aldehydes (1 mmol),malononitrile (1 mmol) and dimedone (1 mmol) in a round bottomflask, and the resultant mixture was stirred magnetically under solvent-free conditions at roomtemperature. After completion of the reaction,as monitored by TLC n-hexane/ethyl acetate (5:2), ethyl acetate(10 mL) was added to the reaction mixture, stirred and refluxed for3 min, and then was washed with water (10 mL) and decanted to separatecatalyst from the other materials (the reaction mixture was solublein hot ethyl acetate and nano structure molten salt catalyst wassoluble in water). The aqueous layer was decanted and the catalystwas separated after removing water. The remained catalyst was usedfor the alternative reaction. The solvent of organic layerwas evaporatedand the crude productwas purified by recrystallization in ethanol/water(10:1). In the present work, nano structure molten salt catalyst wasrecycled and reused for four timeswithout important loss of its catalyticactivity. |
93% | With water extract of lemon peel soaked ash In water for 0.05h; Sealed tube; Irradiation; Heating; | |
92% | With potassium <i>tert</i>-butylate In tetrahydrofuran; methanol at 20℃; | General procedure for synthesis General procedure: A mixture of aromatic aldehydes (1.2 mmol), malonitrile (1 mmol), dimedone (1 mmol) areintroduced in 100 mL of round bottom flask, methanol was added gradually until the mixturewas dissolved. A catalytic amount of potassium tertiary buyoxide and THF added to the abovemiture. The reaction mixture was carried out on the magnetic stirrer under RT condition. Theprogress of the reaction was monitored by TLC in ethylacetate:n-hexane (3:7). After completionof the reaction, the mixture was cooled to room temperature and poured on 10 mL ice coldwater. The crude was filtered and washed with ethylacetate and a saturated solution ofanhydrous sodium bicarbonate several times. The solid product can be separated by columnchromatography (ethylacetate:n-hexane, 3:7) (Scheme 1). |
92% | With HO(1-)*C12H15N2O(1+) In ethanol; water at 50℃; for 0.333333h; Green chemistry; | |
91% | With 2,2'-(ethane-1,2-diylbis[oxy])bis(ethan-1-aminium) 2,2,2-trifluoroacetate In neat liquid at 70℃; for 0.366667h; Green chemistry; | |
82% | With nano-magnetic-supported phenyltetrazolethiol-based Ni complex prepererd by coating Fe3O4 magnetic nanoparticles with tetraethylorthosilicate, further functionalization with 3-chloropropyl-trimethoxysilane and 1-phenyl-1H-tetrazole-5-thiol ligands and the further complexation with nickel nitrate In neat (no solvent) at 75℃; for 0.583333h; | General procedure for the synthesis of chromenes General procedure: The mixture of aldehyde (1.0 mmol), dimedone (140 mg, 1.0 mmol) malononitrile (66 mg, 1.0 mmol) and the phenyltetrazolethiol-based nickel complex (10 mg) was stirred under solvent-free condition at 75 °C for an appropriate time (Fig. 11). After completion of the reaction (TLC, n-hexane/ethyl acetate, 7:3), theresulting mixture was washed with acetone and filtered to separate the catalyst. The solvent was removed, and the crude product was purified by recrystallization in ethanol to yield the pure product. |
With dendrimeric silica-coated Fe3O4 magnetic nanoparticles cores with amino cobalt phthalocyanine tags In neat (no solvent) at 20℃; for 0.3h; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With 1-methylimidazolium tricyanomethanide In neat (no solvent) at 20℃; for 0.2h; Green chemistry; | 2.3. General procedure for the synthesis of 3,4-dihydropyrano[c]chromenederivatives General procedure: [HMIM]C(CN)3} as a NMS catalyst (0.5 mol%) was added to a mixtureof several aromatic aldehydes (1 mmol), malononitrile (1 mmol)and 4-hydroxycoumain (1mmol) in a round bottomflask, and the subsequentmixturewas stirredmagnetically under solvent-free conditionsat room temperature. After completion of the reaction, as checked byTLC n-hexane/ethyl acetate (5:3), ethyl acetate (10 mL) was added tothe reaction mixture, stirred and refluxed for 3 min, and then waswashed with water (10 mL) and decanted to separate catalyst fromthe other materials (the reaction mixture was soluble in hot ethyl acetateand nano structure molten salt catalyst was soluble in water). Theaqueous layer was decanted and the catalyst was separated after removingwater. The remained catalyst was used for the alternative reaction.The solvent of organic layerwas evaporated and the crude productwas purified by recrystallization in ethanol/water (10:1). In the presentwork, NMS catalyst was recycled and reused for four times without importantloss of its catalytic activity. |
94% | With Zn(II)-salicylaldehyde Schiff base complex anchored on silica-coated CaO nanoparticles at 25℃; for 0.333333h; | |
85% | With (N-propyl)-1,3,5,7-tetraazaadamantan-1-ium chloride functionalized silica-coated calcium oxide nano hybrid In water at 20℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84.9% | With sodium acetate; acetic acid; for 7h;Reflux; | General procedure: The desired compounds, (Z)-5-(substituted benzylidene)-2-iminothiazolidin-4-one analogues (1a- 1l) (Figure 1), were prepared by Knoevenagel condensation.With one exception, refluxing a solution of appropriate benzaldehydes and <strong>[556-90-1]pseudothiohydantoin</strong>in acetic acid in the presence of NaOAc produced (Z)-5-benzylidene-2-iminothiazolidin-4-ones as a single stereoisomer in yields of 41.4-94.1%. A Knoevenagel condensation between 2,4-dimethoxy benzaldehyde and <strong>[556-90-1]pseudothiohydantoin</strong> under the same conditions gave amixture of (E)- and (Z)-5-(2,4-dimethoxybenzylidene)-2-iminothiazolidin-4-ones. These compounds could not be easily separated by conventional silica gel column chromatography. Milder reaction conditions capable of accomplishing the Knoevenagel condensation were needed to synthesize only (Z)-stereoisomer. Interestingly,heating a solution of 2,4-dimethoxy benzaldehyde and <strong>[556-90-1]pseudothiohydantoin</strong> in ethanol:H2O (1:1) in the presence of 1.0 equiv. of piperidine as a base catalyst at 80 C afforded the corresponding (Z)-stereoisomer(1l) as a sole product. A suspension of an appropriate benzaldehyde (300 mg, 1.53-2.46 mmol), <strong>[556-90-1]pseudothiohydantoin</strong>(1.1 eq.), and sodium acetate (3.0 eq.) in acetic acid (1 mL/1 mmol of benzaldehyde) was refluxed for 3-7 h. The reaction mixture was cooled and water was added. The resulting precipitates were filtered, and washed with water and, if necessary, a small amountof methylene chloride or ethyl acetate, to produce (Z)-5-(substituted benzylidene)-2-iminothiazolidin-4-oneproducts (1a - 1k) in 41.4-94.1% yields. The resulting precipitates were filtered, and washed with water,ethyl acetate and methylene chloride to give (Z)-5-(2,4-dimethoxybenzylidene)-2-iminothiazolidin-4-one (1l) all final products were confirmed by 1H and 13C NMR spectroscopy and mass spectroscopy. |
41% | General procedure: To the magnetically stirred solution of 17 (232 mg, 2 mmol) in HOAc (7 mL), was added NaOAc (500 mg, 6 mmol). After 15 min 3,4-dimethoxybenzaldhyde (16a, 400 mg, 2.4 mmol) was added and the reaction mixture was heated under reflux for 72 h. The HOAc was removed under reduced pressure and the resultant solid was washed successively with water, methanol and EtOAc to obtain the desired products as solid. 10.2.1.10 5-(3-Ethoxy-4-hydroxybenzylidene)-2-iminothiazolidin-4-one (14j) Yellow solid; mp > 200 C, 216 mg, 41% yield; IR (neat) numax = 3395, 3120, 2759, 1689, 1585 cm-1; 1H NMR (400 MHz, CD3SOCD3) delta 12.50 (s, 1H) 9.88 (s, 1H), 7.69 (s, 1H), 7.13 (s, 1H), 7.04 (d, J = 7.98, 1H), 6.93 (d, J = 8.2, 1H), 4.06-4.05 (m, 2H), 2.07 (s, 1H), 1.34 (t, J = 6.92, 3H); 13C NMR (100 MHz, CD3SOCD3): delta 168.51, 167.92, 150.11, 147.56, 133.12, 124.80, 124.64, 119.56, 116.69, 115.62, 64.34, 15.07; HRMS (ESI-TOF): m/z calculated for C12H12N2O3S [M+H]+, 265.0647; found 265.0637. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In methanol; at 20℃; for 3h; | General procedure: Compounds (3-16) were prepared according to a literature procedure reported earlier by our group10. Compound 2 (2.46 g,10 mmol) was dissolved in methanol (15 mL). The mixture wasstirred until a clear solution was obtained. After that, the appropriate (hetero)aromatic aldehydes were added (11 mmol) andthe solution was stirred at room temperature for 3 h. The precipitate obtained was fltered o, dried, and recrystallized fromethanol.The analytical and spectral data of compounds (3-16) werereported earlier10. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90% | With aluminatesulfonic acid In neat (no solvent) at 80℃; for 0.316667h; Green chemistry; | General procedure for the preparation of 1-amidoalkyl-2-naphthols and 1-(a-aminoalkyl)-2-naphthols General procedure: In a round-bottom flask, the aldehydes (1 mmol), bnaphthol(1 mmol), nitrogen sources (1 mmol, amides and amine for amidoalkyl naphthols and aminoalkyl naphthol,respectively), and ASA NPs (0.1 mmol) were mixed thoroughly.The flask was heated at 80 C with concomitantstirring. The reaction was monitored by thin-layer chromatography(n-hexaneeEtOAc, 3:1). After completion ofthe reaction, hot ethanol (5 mL) was added and the obtainedmixture was filtered and then washed with ethanolto separate the pure catalyst. The solvent was then evaporatedand the crude products were recrystallized inethanol to give pure products. The recovered catalyst wasdried and reused for subsequent runs. The following is thephysical and spectral data of new compounds |
85% | With polyvinylpyrrolidone immobilized on ionic liquid-modified silica-coated Fe3O4 magnetic nanoparticles In neat (no solvent) at 80℃; for 0.75h; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With aluminium(III) iodide In dimethyl sulfoxide; acetonitrile at 80℃; for 18h; | 17 Example 17 (ethyl vanillin deethylation) To a 100 ml eggplant-shaped flask, aluminum triiodide (2.240 g, 5.5 mmol), acetonitrile (40 ml) and DMSO (0.430 gj 5.5 mmol) were added, and the mixture was heated to 80 ° C with stirring, and kept under stirring for 0.5 hour, followed by addition. Ethyl vanillin (0.831 g, 5.0 mmol), stirring was continued (80 ° C), the reaction was stopped after 18 hours, and after cooling to room temperature, acidification was carried out by adding 2 mol/L of dilute hydrochloric acid (10 ml) to the eggplant flask. The mixture was extracted with EtOAc (EtOAc (EtOAc)EtOAc. The evaporating apparatus was evaporated to dryness, and the residue was purified by flash column chromatography (ethyl acetate / petroleum ether = 1:4, volume ratio) to give 0.662 g of 3,4-dihydroxybenzaldehyde (white solid, yield 96%). |
95% | With aluminium(III) iodide; dimethyl sulfoxide In acetonitrile at 80℃; for 18h; | Cleavage of Catechol Monoalkyl Ethers by Aluminum Triiodide- Dimethyl Sulfoxide; General Procedure General procedure: To a suspension of AlI3 (5.5 mmol, 1.1 equiv) in MeCN was added anhyd DMSO (0.430 g, 5.5 mmol, 1.1 equiv). After stirring for 0.5 h at 80 °C, the selected substrate (5 mmol) was added in one portion. The mixture was stirred overnight (18 h) at that temperature before quenching with aq 2 M HCl (10 mL). After extraction with EtOAc (3 50 mL), the organic phases were combined, washed with sat. aq Na2S2O3 and brine, and dried (MgSO4). The solvents were removed on a rotary evaporator, and the residue was purified by column chromatography to give the relevant catechol or phenol. |
93% | With aluminium(III) iodide; calcium oxide In acetonitrile at 80℃; for 18h; | 8 Example 8 (ethyl vanillin deethylation) To a 100 ml eggplant flask was added aluminum triiodide (2.242 g, 5.5 mmol), acetonitrile (40 ml),CaO (0.422 g, 7.5 mmol, 1.5 eq) and ethyl vanillin (0.833 g, 5.0 mmol) were heated to 80 °C,After 18 hours of reaction, stirring was stopped. After cooling to room temperature, 2 mol/L dilute hydrochloric acid (10 ml) was acidified in an eggplant-shaped flask.Extract with ethyl acetate (50ml x 3) and combine the organic phases and wash first with saturated aqueous sodium thiosulfate (10ml).It was washed with saturated brine (10 ml), dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated to dryness on a rotary evaporator.The residue was purified by flash column chromatography (eluent: ethyl acetate/petroleum ether=1:2, volume ratio).0.646 g of 3,4-dihydroxybenzaldehyde was obtained (white solid, yield 93%). |
82% | With aluminium(III) iodide; diisopropyl-carbodiimide In acetonitrile at 80℃; for 18h; | Hydroxychavicol (4-Allylbenzene-1,2-diol, 2); General Procedure General procedure: To a suspension of AlI3 (5.5 mmol, 1.1 equiv) in hot CH3CN (40 mL) were added sequentially DIC (0.379 g, 3 mmol, 0.6 equiv) and eugenol (1, 0.821 g, 5.0 mmol). The mixture was stirred for 18 h at 80 °C, and then it was cooled to r.t., acidified with HCl (2 mol/L, 10 mL), and extracted with EtOAc (3 × 50 mL). The organic phases were combined, washed with sat. aq Na2S2O3 (10 mL) and brine (10 mL), and was dried (MgSO4). The solvent was removed on a rotary evaporator and the residue was purified by flash column chromatography (PE/EtOAc, 4:1) to afford 2 (0.750 g, 99%) as a white solid |
82% | With aluminium(III) iodide; diisopropyl-carbodiimide In acetonitrile at 80℃; for 18h; | 24 Example 24 (ethyl vanillin deethyl) To a 100 ml eggplant flask were added aluminum triiodide (2.248 g), acetonitrile (40 ml) DIC (0.375 g) and ethyl vanillin (0.832 g) were heated to 80 ° C and the reaction was continued for 18 hours. After cooling to room temperature, 2 mol / L dilute hydrochloric acid (10 ml) was added to the eggplant flask and acidified with ethyl acetate (50 ml X) The combined organic phases were washed with saturated aqueous sodium thiosulfate (10 ml), washed with saturated brine (10 ml), dried over anhydrous magnesium sulfate, filtered and the filtrate was evaporated to dryness using a rotary evaporator. The residue was passed through a flash column Analysis (Eluent: ethyl acetate / petroleum ether = 1: 1, volume ratio) to give 0.567 g of 3,4-dihydroxybenzaldehyde (white solid in 82% yield) |
60% | With aluminium(III) iodide; <i>N</i>,<i>N</i>-dimethyl-formamide dimethyl acetal In acetonitrile at 80℃; for 18h; | |
59% | With pyridine; aluminium(III) iodide In acetonitrile at 80℃; for 18h; | General procedure: To a solution of AlI3 (36.6 mmol, 1.1 equiv) in MeCN (100 mL)was added dropwise a solution of pyridine (12.2 g, 154.2 mmol,4.6 equiv) and eugenol (5.4 g, 33.0 mmol). The mixture wasstirred at 80 °C for 18 h. After cooling to room temperature, themixture was quenched with aq HCl (2 mol/L, 50 mL), and wasextracted with EtOAc (4 × 50 mL). The combined organic phaseswere washed with brine and dried by MgSO4. After evaporationof solvents by a rotary evaporator, the residue was purifiedthrough flash column chromatography to afford 5 as a whitesolid (4.9 g, 99%). |
59% | Stage #1: 4-hydroxy-3-ethoxybenzaldehyde With pyridine; iodine; aluminium In acetonitrile for 18h; Reflux; Stage #2: With hydrogenchloride In water; acetonitrile at 20℃; | 8 Example 8 (ethyl vanillin demethylation) To a 100 ml eggplant flask were added iodine (2.099 g), aluminum powder (0.637 g) and acetonitrile (50 ml), heated toReflux, stir for 2 hours to the purple red of iodine disappears. Then pyridine (1.601 g) and ethyl vanillin (0.832 g) were added and the reaction was continuedShould be 18 hours. After stirring at room temperature, 2 mol / L dilute hydrochloric acid (10 ml) was added to the reaction solution, and the mixture was extracted with ethyl acetate(50 ml x 3). The organic phases were combined and dried over anhydrous sodium sulfate. The filtrate was evaporated to dryness with a rotary evaporator and the residue passed throughThe residue was purified by flash column chromatography (mobile phase ethyl acetate: petroleum ether = 1: 1, volume ratio) to give 3,4-dihydroxybenzaldehyde (whiteColor solid, 0.412 g, yield 59%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 24h; | 1.3.1 2.2.5. synthesis of 4'-(4-benzyloxy-3-ethoxybenzaldehyde)-2,2':6',2''-terpyridine (BEBtpy) (L3) General procedure: To a solution of 4-hydroxybenzaldehyde (0.242 g, 1.98 mmol) in 6 ml of dry DMF were added anhydrous potassium carbonate(0.305 g, 2.2 mmol) and Brttpy (0.8 g, 1.98 mmol). The reaction was stirred at 80 °C for 24 h, and the reaction mixture was cooled then poured into 100 ml of water and extracted with ethyl acetate. The combined organic phases were washed with water, brine solution and dried over anhydrous sodium sulfate and the solvent was evaporated on a rotary evaporator. The residue was purified by column chromatography (neutral alumina, hexane/ethylacetate 4:1) to give the product as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With hydrogen at 40℃; for 23h; Industrial scale; | 12 1 kg of ethyl vanillin, 6 liters of isopropanol (concentration of ethyl vanillin at lmol / L), 0.3 kg of catalyst B and 0.15 kg of catalyst F were added to the kettle and charged with IMPa hydrogen, Heated to 40 ° C reaction 23h, the detection of ethyl vanillin reaction is complete, stop heating, after the reactor cooling filter catalyst, the catalyst directly after drying. The filtrate was subjected to rotary evaporation to remove excess isopropanol to give 1.33 kg of ethyl vanillin isopropyl ether, 96% yield and 98% purity. |
42% | With C18H4BCl3F8; hydrogen at 55℃; for 72h; Molecular sieve; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With aluminum oxide; In dichloromethane; at 20℃;Inert atmosphere; | General procedure: To a solution of benzofuran-3(2H)-one (1.0 mmol) and benzaldehyde(1.0 mmol) in dichloromethane (6 mL) was addedaluminum oxide (30.0 mmol) at room temperature. After stirringfor 6 h, the reaction mixture was filtered off. The filtrate wasconcentrated under vacuum and the residue was purified by flash chromatography on silica gel to give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With aluminum oxide; In dichloromethane; at 20℃;Inert atmosphere; | General procedure: To a solution of benzofuran-3(2H)-one (1.0 mmol) and benzaldehyde(1.0 mmol) in dichloromethane (6 mL) was addedaluminum oxide (30.0 mmol) at room temperature. After stirringfor 6 h, the reaction mixture was filtered off. The filtrate wasconcentrated under vacuum and the residue was purified by flash chromatography on silica gel to give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
30% | With aluminum oxide; In dichloromethane; at 20℃;Inert atmosphere; | General procedure: To a solution of benzofuran-3(2H)-one (1.0 mmol) and benzaldehyde(1.0 mmol) in dichloromethane (6 mL) was addedaluminum oxide (30.0 mmol) at room temperature. After stirringfor 6 h, the reaction mixture was filtered off. The filtrate wasconcentrated under vacuum and the residue was purified by flash chromatography on silica gel to give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | With aluminum oxide; In dichloromethane; at 20℃;Inert atmosphere; | General procedure: To a solution of benzofuran-3(2H)-one (1.0 mmol) and benzaldehyde(1.0 mmol) in dichloromethane (6 mL) was addedaluminum oxide (30.0 mmol) at room temperature. After stirringfor 6 h, the reaction mixture was filtered off. The filtrate wasconcentrated under vacuum and the residue was purified by flash chromatography on silica gel to give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With aluminum oxide; In dichloromethane; at 20℃;Inert atmosphere; | General procedure: To a solution of benzofuran-3(2H)-one (1.0 mmol) and benzaldehyde(1.0 mmol) in dichloromethane (6 mL) was addedaluminum oxide (30.0 mmol) at room temperature. After stirringfor 6 h, the reaction mixture was filtered off. The filtrate wasconcentrated under vacuum and the residue was purified by flash chromatography on silica gel to give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With aluminum oxide; In dichloromethane; at 20℃;Inert atmosphere; | General procedure: To a solution of benzofuran-3(2H)-one (1.0 mmol) and benzaldehyde(1.0 mmol) in dichloromethane (6 mL) was addedaluminum oxide (30.0 mmol) at room temperature. After stirringfor 6 h, the reaction mixture was filtered off. The filtrate wasconcentrated under vacuum and the residue was purified by flash chromatography on silica gel to give the desired compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With acetic acid In ethanol at 80 - 90℃; for 0.3h; Microwave irradiation; | B. Microwave-assisted method [37] General procedure: Solvent-free synthesis of Schiff’s bases was achieved by cyclo addition of various suitablealdehydes (6) (0.01 mol) and N-((5-amino-1,3,4-thiadiazol-2-yl)methyl) benzamide (5) (0.01 mol) in thepresence of a catalytic amount of glacial acetic acid under microwave irradiation at 250Wfor 8-20 min,as shown in Scheme 1. The completion of the reaction was monitored by TLC. The synthesized productswere recrystallized from ethanol. The same compounds were also synthesized using conventionalapproach. A comparative study in terms of yield and reaction period has been reported for bothmicrowave-assisted and conventional methods. The conventional method required about 3-8 h, whilethe microwave-irradiation method required only 8±20 min, as shown in Table 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | With sodium hydroxide In ethanol at 20℃; for 24h; | 4.2.1. 4-(3-Ethoxy-4-hydroxyphenyl)but-3-en-2-one (21) To a solution of ethylvanillin (20, 50.0 g, 0.3 mol) in acetone(176 mL) and in ethanol (319 mL) was added 15% aqueous NaOH solution (180 mL). The mixture was stirred at room temperature for24 h, and it was quenched with 2M aqueous HCl solution (352 mL,pH~3). After extraction with EtOAc (4 200 mL), the combinedorganic layer was washed with water, brine and dried over Na2SO4.The solvent was evaporated in vacuo to afford 21 (93%) as a yellow solid, which was used without further purification. M.p.: 98 °C(Ref. [64] 104-105 °C); its spectral data were found to be identical with the ones described in Ref. [64]. |
With sodium hydroxide In water at 20℃; for 48h; | ||
Stage #1: 4-hydroxy-3-ethoxybenzaldehyde; acetone With sodium hydroxide In water Stage #2: With hydrogenchloride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With triethylamine sulfate In neat (no solvent) at 20℃; Green chemistry; | 3.2. Synthesis of 3-((Dicyclohexylamino)(substituted phenyl/heteryl)methyl)-4-hydroxy-2H-chromen-2-oneDerivatives 4a-o General procedure: A mixture of a suitable aldehyde 1a-o (1.25 mmol), dicyclohexyamine (2) (1.25 mmol),4-hydroxy-coumarin (3) (1.25 mmol), and 20 mol% of [Et3NH][HSO4] as catalyst were taken in a25 mL of beaker and the reaction mixture was stirred at room temperature. After completion of thereaction (monitored by TLC), the mixture was poured into ice cold water. The product obtained,was filtered and dried. The corresponding product was obtained in high purity after recrystallizationof the crude product from ethanol. The authenticity of the synthesized compounds was established by1H-NMR, 13C-NMR, IR, Mass spectra and elemental analyses. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With acetic acid; In ethanol;Reflux; | General procedure: General procedure for the synthesis of hydrazones (4-36): Compound 3 (1 mmol) was dissolved in ethanol (10 mL/g of compound) and treated with appropriate aldehydes (2 mmol) in the presence of catalytic amount of glacial acetic acid. The reaction mixtures were refluxed for 7-8 hr and the completion of reaction was monitored by TLC. After completion of the reaction, the solvent was removed under reduced pressure and cooled by adding ice cold water. The resulting precipitate was filtered, washed with water and recrystallized from ethanol to obtain the desired dihydrazones (4-36). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With MIL-100(Cr)/NHEtN(CH2PO3H2)2; In N,N-dimethyl-formamide; at 100℃; for 0.25h; | General procedure: In a 10 mL round-bottomed flask, a mixture of aldehyde (1 mmol),uracil derivatives (1 mmol), dimedone (1 mmol, 0.14 g) and MIL-100(Cr)/NHEtN(CH2PO3H2)2 (0.01 g) were stirred at 100 C in DMF(5 ml) as solvent. After completion of the reaction as monitored by TLC,the reaction mixture was cooled to room temperature. Then, the catalystwas separated from the solution of reaction mixture by centrifugation(1000 rpm). Then, H2O (5 ml) was added to reaction mixtureto give the solid sediment. The prepared solid was collected by simplefiltration. The crude product was purified by recrystallization fromEtOAc (Scheme 3). The pure products were identified by FT-IR, 1H, 13CNMR and mass spectra. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | In ethanol; for 6h;Reflux; | General procedure: A mixture of methyl 3,4-dimethoxybenzoate (1mmol) and corresponding benzaldehyde (1mmol) was refluxed in ethanol (7ml) for 6h. Reaction completion was checked by TLC. The mixture was cooled to room temperature and the resulted precipitate was collected and washed with diethyl ether to yield the final pure products. Moreover, in some cases, recrystallization in appropriate solvents was done in order to obtain the pure derivatives. 2.4.1 (E)-3,4-dimethoxy-N'-(4-nitrobenzylidene)benzohydrazide (D1) Yellow solid; yield: 82%; M.P: 208-210C. 1H NMR (300MHz, DMSO-d6): δ (ppm) 3.85 (s, 6H, OCH3), 7.09 (d, 1H, Ar-H-5, J=6.5Hz), 7.42-7.58 (m, 2H, Ar-H-2, 6), 7.96 (d, 2H, Ar-H-2′,6′), 8.28 (d, 2H, Ar-H-3′,5′), 8.55 (s, 1H, N=CH), 12.00 (s, 1H, NH). 13C NMR (75MHz, DMSO-d6): δ (ppm) 56.10 (OCH3), 56.14 (OCH3), 111.46, 121.66, 121.70, 124.52, 125.53, 128.32, 141.26, 145.06, 148.20, 148.86, 152.45, 163.24 (C=O). MS (EI, 70eV): m/z (%)=329 (M+, 10), 165 (100). Anal. Calcd for C16H15N3O5: C 58.36, H 4.59, N 12.76%, found: C 58.44, H 4.61, N 12.72%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 91% 2: 5.3% | Stage #1: 4-hydroxy-benzaldehyde With bromine In methanol; chloroform at 0 - 5℃; Stage #2: sodium ethanolate With copper(II) carbonate In ethanol; N,N-dimethyl-formamide at 110 - 120℃; for 3h; Inert atmosphere; | 2 Bromination of p-hydroxybenzaldehydeIn the reactor, 24.4 g (0.2 mol) of p-hydroxybenzaldehyde, 160 ml of methanol, and 250 ml of chloroform were sequentially added, and the mixture was stirred and cooled to 0-5 ° C in an ice water bath. Take 36.8 g of bromine (0.23 mol), dissolve it in 75 ml of chloroform to make a solution, and slowly add it to the reactor dropwise for about 1.5-2 hours, and continue to react for 2.5 hours after the drop. After completion of the reaction, nitrogen bromide and bromine remaining in the system were purged with nitrogen to obtain a reaction completion liquid.The reaction completion liquid is heated, and chloroform and a part of methanol are distilled off to obtain a brominated product, which is directly used as a raw material for vanillin synthesis. The composition and mass fraction of the brominated product was determined to be 93.2% of 3-bromo-p-hydroxybenzaldehyde, and 6.3% of 3,5-dibromo-p-hydroxybenzaldehyde.During the dropwise addition, the hydrogen bromide gas is removed with a slight negative pressure, and it enters the absorption oxidation and chloroform extraction device to make a bromine chloroform solution for recycling.2. Synthesis of methyl vanillinAdd 0.64 moles of sodium methoxide (28% methanol solution) and 80 ml of methanol to the aforementioned reactor of brominated products (0.2 moles), stir well, and then add 1.5 g of copper oxide and dimethylformamide (DMF) in this order. 10 ml. After replacing the air with nitrogen, the temperature was raised to 115 ° C-120 ° C (pressure about 0.5 MPa-0.6 MPa), and the reaction was carried out for 4 hours. The reaction was terminated by cooling to room temperature. The reaction mixture was distilled off methanol. Add 100 ml of water, add 1 g of powdered activated carbon, heat up to 95 ° C with stirring, decolorize for half an hour, filter while hot, cool the filtrate to 60 ° C, neutralize with concentrated hydrochloric acid to pH = 3.6, and precipitate.Continue to cool to 10 ° C, filter, wash and dry the filter cake to obtain a mixture of vanillin and syringaldehyde.3. Pure vanillin and syringaldehyde can be obtained by refining and separating using techniques known in the art; The solvent methanol in Example 1 was replaced by ethanol, and a brominated product (0.2 mol) was charged with 0.7 mol of sodium ethoxide in ethanol, 70 ml of ethanol was stirred and dissolved, and 2.2 g of basic copper carbonate and dimethylformaldehyde were added 12 g of amide (DMF), the air was replaced with nitrogen, and the temperature was raised to 110 ° C-120 ° C (pressure about 0.5MPa-0.6MPa). After 4 hours of reaction, the reaction was cooled to room temperature to terminate the reaction. The reaction mixture was distilled off ethanol and recovered for reuse. Add 350 ml of water, 2 g of powdered activated carbon, heat up to 95 ° C with stirring, decolorize with heat preservation, and filter while hot. The filtrate is cooled to 60 ° C, neutralized with concentrated hydrochloric acid to pH = 2-3, precipitated, and cooled to 10 ° C Filtering, washing and drying to obtain a mixture of ethyl vanillin and 3.5-diethoxy-4-hydroxybenzaldehyde;The yields of ethyl vanillin and 3.5-diethoxy-4-hydroxybenzaldehyde were 91% and 5.3%, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56% | With hydrogenchloride; acetic acid at 20 - 40℃; for 48h; Sealed tube; | Synthesis of Curcumin Analogs General procedure: Curcumin analogs were synthesized as described, with some modifications. In short, piperidin-4-one (10.0 mmol) was added into a flask with a mixture of 24.0 mmol of aldehyde compound in 40 - 60 mL of saturated HCl-CH3CO2H, which was then sealed and placed at 20 - 40 °C for 48 hours. Ultrasonic oscillation was employed to dissolve aldehyde compound when necessary. The mixture was subsequently poured into 300 mL of water with stirring, and the solid product was obtained by filtration. The filter cake was grounded and washed twice with ethanol using ultrasonic oscillation, and the pure product was obtained by further filtration and dehydration. The structure characterization of some target compounds is showed below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; at 80℃; | General procedure: A solution of <strong>[32058-82-5]5-(4-aminophenyl)-1,3,4-oxadiazole-2-thiol</strong>(0.107 g, 0.5 mmol) in 5 ml ethanol was added drop-wise to the solution of substituted aldehydes (0.5 mmol) in ethanol. Thereaction mixture was refluxed at 80 C for 30 min to 22 h. Tomonitor the reaction progress and purity of compounds TLC wasused in ethyl acetate and hexane (1:3). The coloured precipitateswere filtered, washed with ethanol and then dry in vaccum dessicator over fused CaCl2. The synthetic route for the heterocyclicderivatives 2a-2l is shown in the Scheme 1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol at 40 - 50℃; for 4h; | 3 Embodiment 3 S1: the vanillin derivative is dissolved in an organic solvent to obtain a mixed solution;S2: dropwise add 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane to the mixed solution in S1 according to the preset addition amount;S3: After the dropwise addition is completed, after reacting at a preset temperature for a preset time, distillation, washing and drying are performed in sequence to obtain a toughening agent.Specifically, ethyl vanillin (29 mmol) and ethanol (40 mL) were sequentially added to the three-necked flask, and after stirring to dissolve, 1,3-bis(3-aminopropyl)-1,1,3,3-tetramethyldisiloxane (13.2mmol) was added under the condition of 40°C, was slowly dropped into the three-necked flask. After the dropwise addition, the reaction was carried out at 50°C for 4h. After the reaction was completed, it was obtained by distillation, washing and drying. Toughening agent, the structural formula of the toughening agent is:Wherein, R=3-ethoxy-4-hydroxyphenyl. |
Tags: 121-32-4 synthesis path| 121-32-4 SDS| 121-32-4 COA| 121-32-4 purity| 121-32-4 application| 121-32-4 NMR| 121-32-4 COA| 121-32-4 structure
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