Structure of 56442-17-2
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CAS No. : | 56442-17-2 |
Formula : | C14H11FO2 |
M.W : | 230.23 |
SMILES Code : | O=CC1=CC=C(OCC2=CC=C(F)C=C2)C=C1 |
MDL No. : | MFCD00173650 |
InChI Key : | QGULWBQOCMQNFD-UHFFFAOYSA-N |
Pubchem ID : | 735860 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P233-P260-P261-P264-P271-P280-P302+P352-P304-P304+P340-P305+P351+P338-P312-P321-P332+P313-P337+P313-P340-P362-P403-P403+P233-P405-P501 |
* 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 |
---|---|---|
85% | With potassium carbonate; potassium iodide; In N,N-dimethyl-formamide; at 100℃; for 3h; | General procedure: Aldehydes2 and 3 were synthesized by alkylation of 4-hydroxybenzaldehydeaccording to modified procedure[11]. A mixture of 30 mL of DMF, 6.1 g (50 mmol) of4-hydroxybenzaldehyde, 48 mmol of benzyl or 4-fluorobenzyl chloride, 6.9 g (50 mmol) of potassium carbonate , and 83 mg (0.5 mmol) of potassium iodide was heated for 3 h at 100C on an oil bath. The mixture was cooled to room temperature and dilutedwith 200 mL of water, and the precipitate was filtered off, washed several times with water, and dried. |
84% | With potassium carbonate; In N,N-dimethyl-formamide; at 120℃; for 12h; | A mixture of 10 mmol of p-hydroxy benzaldehyde(1) and 10 mmol of 1-(chloromethyl)-4-fluorobenzene (2) in DMF was stirred at 120 C for 12 hours using K2CO3 as a catalyst. The reaction mixture was poured in crushed ice.The crude product 4-((4-fluorobenzyl)oxy) benzaldehyde(3) was isolated and recrystallized from absolute hot ethanol.Yield: 84% M.P: 99 C. |
With potassium carbonate; In acetonitrile; at 80℃; | General procedure: A mixture of 4-hydroxybenzaldehyde (1.0 g, 8.2 mmol), K2CO3 (2.2 g, 8.2 mmol), and alkyl bromide or benzyl chloride derivatives (8.2 mmol) were placed into a round bottomed flask containing 30 mL of acetonitrile. The mixture was then stirred and heated at 80 C for 12-24 h. After the completion of the reaction, the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (30 mL), washed with water (10 mL 3), and then dried over anhydrous MgSO4 to give compounds 6a-w. |
With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; | General procedure: Toa solution consisting of 4-hydroxybenzaldehyde (10 mmol) or 6-hydroxy-2-naphthaldehyde (10 mmol) and K2CO3(10 mmol) in dry DMF (20 mL), the corresponding substituted benzyl chloride (10mmol) was added to the stirred solution 8-12 h at 60 oC. After the reaction is completed, the mixture waspoured into ice water, after which it solidifies. The resulting precipitate wasfiltered, washed with ethanol and recrystallized with ethanol to obtain crudeproducts which purifiedby column chromatography (dichloromethane : petroleum ether = 10 : 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98.5% | toluene-4-sulfonic acid; | Example 47 Synthesis of α-[4-(4-Fluorobenzyloxy)phenyl]-N-tert-butylnitrone The title compound was prepared by refluxing a benzene solution of <strong>[56442-17-2]4-(4-fluorobenzyloxy)benzaldehyde</strong> and N-tert-butylhydroxylamine for 21 hours with p-toluenesulfonic acid as a catalyst. The title compound was obtained as a solid in 98.5% yield, m.p. 180.3 C. (Rf =0.16 on a silica gel plate using hexanes: EtOAc, 1:1, v/v, as an eluant). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91.15% | With sodium acetate; In acetic acid; for 7h;Reflux; | To a stirred solution of 4-(4-Fluoro-benzyloxy)-benzaldehyde (250 mg, 1.09 mmol) , rhodanine (145 mg., 1.09 mmol) in acetic acid (10 ml) was added sodium acetate (357 mg, 4.36 mmol) and heated under reflux for 7 h . After cooling to room temperature, water (15ml) was added and solid precipitate was filtered ,washed with water (10ml) and hexane(10 ml) and dried under vacuum to afford a yellow solid product (340 mg , 91.15%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium carbonate; In N,N-dimethyl-formamide; at 20 - 60℃; | To a stirred solution of 4-hydroxy benzaldehyde (2g, 16.39 mmol) in N, N- dimethylformamide (20 ml) at room temperature was added potassium carbonate (3.4 g, 24.59 mmol) and p-fluorobenzyl bromide (3.1 g, 16.40 mmol). The reaction mixture was heated to 60 C for 2 h. The reaction mixture was cooled to room temperature, poured in to cold water (50 ml) and precipitated solid was filtered, washed with water (100 ml) and dried under vacuum to afford off white solid (3.70 g, 98 %).1H NMR (CDCl3) δ: 5.11 (s, 2H), 7.06 - 7.11 (m, 4H), 7.39 - 7.43 (dd, 2H), 7.83 - 7.85 (d, 2H), 9.89 (s, IH). |
98% | With potassium carbonate; In N,N-dimethyl-formamide; at 60℃; for 2h; | To a stirred solution of 4-hydroxy benzaldehyde (2g, 16.39 mmol) in N, N- dimethylformamide (60 ml) at room temperature was added potassium carbonate (3.4 g , 24.59 mmol) and p-fluorobenzyl bromide (3.1 g , 16.40 mmol). The reaction mixture was heated at 60 0C for 2 h. The reaction mixture was cooled to room temperature, poured in cold water (50 ml) and precipitated solid was filtered, washed with water (100 ml) and dried under vacuo to afford off white solid (3.70 g , 98 %).1H NMR: 400 MHz (CDCl3) δ 5.11 (s, 2H), 7.06-7.11 (m, 4H), 7.39-7.43(dd, 2H), 7.83- 7.85(d, 2H), 9.89(s, IH). |
97.6% | With potassium carbonate; In acetone;Reflux; Inert atmosphere; | General procedure: A mixture of hydroxybenzaldehyde (6 mmol), substituted benzyl bromide (6 mmol) and potassium carbonate (9 mmol) in acetone (40 ml) was refluxed for 5 h under N2 atmosphere, cooled to room temperature. After evaporation of acetone, the resulting residue was alkalized with a solution of sodium hydroxide (1 M) and extracted with dichloromethane. The organic layer was dried over anhydrous Na2SO4, concentrated to produce the white or light yellow solid. |
95% | With potassium carbonate; In N,N-dimethyl-formamide; at 55℃; for 1h; | Example 2 3-[4-(4-Fluoro-benzyloxy)-phenyl]-isoxazol-4-ylamine To a mixture of 4-hydroxybenzaldehyde (12.2 g, 100 mmol) and K2CO3 (16.6 g, 120 mmol) in DMF (60 mL) was added 4-fluorobenzyl bromide (13.5 mL, 108 mmol) dropwise over 15 min. The brown suspension was warmed to 55 C. for 45 min. The reaction was then cooled to rt and poured into 500 mL ice water. 4-(4-Fluoro-benzyloxy)-benzaldehyde (21.9 g, 95%) was collected as a white solid by filtration. |
65% | With potassium carbonate; In N,N-dimethyl-formamide; at 20℃; for 12h;Inert atmosphere; | General procedure: To a stirred solution of 4-hydroxybenzaldehyde (1 g, 8.2 mmol)in N,N-dimethylformamide (DMF) (30 mL) at room temperaturewas added potassium carbonate (1.7 g,12.3 mmol). Different benzylbromide (8.4 mmol, 1.02 eq) was slowly added. The resultantmixture was stirred overnight under an inert atmosphere at roomtemperature. Subsequently, the solution was evaporated underreduced pressure to remove DMF and then saturated brine wasadded. After that, the mixturewas extracted with ethyl acetate, andthe organic phase was dried over anhydrous MgSO4, and concentratedunder reduced pressure to give the crude product, whichwaspurified by column chromatography [37] gave the corresponding products, 1a-13a. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
43% | With piperidine; In ethanol; for 16h;Reflux; | A mixture of {4-[3-Methyl-4-oxo-thiazolidin-2-ylideneamino]-phenyl} -acetic acid methyl ester (200 mg, 0.72 mmol), <strong>[56442-17-2]4-(4-fluorobenzyloxy)benzaldehyde</strong> (165 mg, 0.72 mmol) and piperidine (0.145 ml, 1.4 mmol) in ethanol (15 ml) was heated under reflux for 16 h. The reaction was monitored by thin layer chromatography. The reaction mixture was cooled to room temperature and solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate (40 ml) and washed with water (2x 10 ml), organic layer was dried over anhydrous sodium sulfate and evaporated under vacuo. The risidue was purified by silica gel column chromatography using ethyl acetate: hexane (15 :85) as eluent to give a yellow solid of 4-[5-[l-[4-(4-Fluoro-benzyloxy)-phenyl]-methylidene]-3-methyl-4-oxo- thiazolidin-2-ylideneamino]-phenyl}-acetic acid methyl ester (160 mg, 43 %). MS = m/z 491 (M+l). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With hydroxylamine hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃;Inert atmosphere; | Example 1 Preparation of 4-(4-fluoro-benzyloxy)-benzaldehyde oxime (intermediate 1) To a mixture of 4-(4-fluoro-benzyloxy)-benzaldehyde and hydroxylamine hydrochloride (0.664 g, 9.56 mmol) in anhydrous DCM (30 ml), at 0 C. under nitrogen atmosphere, TEA (1.332 ml, 9.56 mmol) was added dropwise, and the reaction mixture was stirred at RT overnight. The mixture was directly purified by flash chromatography on silica gel, in gradient elution from petroleum ether/AcOEt 85:15 to ether/AcOEt 70:30 to afford the title compound 1 (2.03 g, 8.28 mmol, 95% yield). LC-MS (ESI POS): 246.0 (MH+) |
95% | With hydroxylamine hydrochloride; triethylamine; In dichloromethane; at 0 - 20℃;Inert atmosphere; | Example 1Preparation of 4-(4-Fluoro-benzyloxy)-benzaldehyde oxime (intermediate 1)To a mixture of 4-(4-Fluoro-benzyloxy)-benzaldehyde and hydroxylamine hydrochloride (0.664 g, 9.56 mmol) in anhydrous DCM (30 ml), at 0 C under nitrogen atmosphere, TEA ( 1.332 ml, 9.56 mmol) was added dropwise and the reaction mixture was stirred at RT overnight. The mixture was directly purified by flash chromatography on silica gel, in gradient elution from petroleum ether/AcOEt 85 : 15 to ether/AcOEt 70 : 30 to afford the title compound 1 (2.03 g, 8.28 mmol, 95 % yield).LC-MS (ESI POS): 246.0 (MH+) |
23.5 g | With hydroxylamine hydrochloride; sodium hydroxide; In ethanol; water; at 20℃; for 2h; | To a suspension of 4-(4-fluoro-benzyloxy)-benzaldehyde (21.9 g, 95.2 mmol) and hydroxylamine hydrochloride (7.3 g, 105 mmol) in 400 mL water/ethanol 9:1 was added a solution of NaOH (9.5 g in 100 mL of water) dropwise over 15 min. The now yellow solution was stirred for 2 h at rt after which the reaction was adjusted to pH 5-6 with acetic acid. The resulting white precipitate was collected by filtration and washed with water. The wet filter cake was dissolved in ethyl acetate and dried over Na2SO4. Filtration followed by removal of volatiles under reduced pressure gave 4-(4-fluoro-benzyloxy)-benzaldehyde oxime (23.5 g, 95.8 mmol) as a yellowish crystalline solid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With piperidine; acetic acid; In ethanol; for 12h;Reflux; | General procedure: To a suspension of 1 (1.1 mmol) in dry ethanol (10 mL), the 4-[(substitutedbenzyl)oxy]benzaldehydes 5a-j (1 mmol), a catalytic amount of piperidine (0.1 mmol) and glacial acetic acid (0.1 mmol) were added. The mixture was stirred and refluxed overnight. After cooling, the solvent was evaporated in vacuo, dried, and purified by silica gel column chromatography (dichloromethane/methanol, 200:1). The yield, melting point and spectral data of each compound are given below. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | With piperidine; In dimethyl sulfoxide; at 20 - 120℃; | General procedure: To a mixture of ethyl 3H-thieno[3′,2′:3,4]benzo[1,2-d][1,2,3]dithiazole-7-carboxylate 2-oxide 3 (150 mg, 0.50 mmol) and aldehyde (1.10 mmol) in DMSO (4 mL) was added piperidine (0.05 mL, 0.50 mmol). The reaction mixture was first stirred overnight at room temperature, and then for 1.5-3 h at 120 C. After cooling, water was added, the precipitate was filtered and dried. The product was purified by recrystallization from ethanol or by column chromatography on silica gel using CH2Cl2 as eluent to afford pure 5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In methanol; at 20℃; for 24h; | General procedure: (b) A mixture of 10 mmol of 3 and 10 mmol of substituted acetophenone (4a-h) in methanol (30 ml) was stirred at room temperature for 24 hours using 20% NaOH as a catalyst to make the solution alkaline. The reaction mixture was poured in ice cold water. The crude 3-(4-((4-fluorobenzyl)oxy)phenyl)-1-phenylprop-2-en-1-one (5a-h) was isolated and recrystallized from hot absolute ethanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide; In methanol; at 20℃; for 24h; | General procedure: (b) A mixture of 10 mmol of 3 and 10 mmol of substituted acetophenone (4a-h) in methanol (30 ml) was stirred at room temperature for 24 hours using 20% NaOH as a catalyst to make the solution alkaline. The reaction mixture was poured in ice cold water. The crude 3-(4-((4-fluorobenzyl)oxy)phenyl)-1-phenylprop-2-en-1-one (5a-h) was isolated and recrystallized from hot absolute ethanol. |
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