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CAS No. : | 61049-69-2 |
Formula : | C13H12O3 |
M.W : | 216.23 |
SMILES Code : | O=C1C(OCC2=CC=CC=C2)=C(C)OC=C1 |
MDL No. : | MFCD00207271 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
75% | With ammonia; In ethanol;Heating / reflux; | To a solution of 2 (13.8g, 0.064mol) in ethanol (25mL) was added ammonia solution (5OmL) and refluxed overnight. The solvent was removed under reduced pressure, then taken into water and adjusted to pH 1 with concentrated hydrochloric acid. The aqueous mixture was washed with ethyl acetate (3x) and the pH was adjusted to pH 10 with sodium hydroxide (2M.). The aqueous phase was extracted with chloroform (3?), dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure. Re-crystallisation from methanol/diethyl ether gave brown cubic crystals, mp 162-164C. Yield 75%. 1H NMR (CDCl3) ? 2.15 (3H, s, CH3), 5.03 (2H, s, CH2Ph), 6.35 (1?, d, J=6.9?z, 5-H), 7.25-7.31 (5?, m, CH2PA), 7.39 (IH, d, J=6.9Hz, 6-/2). C13H13NO2. |
75% | With ammonia; In ethanol;Reflux; | To a solution of 2 (13.8 g, 0.064 mol) in ethanol (25 mL) was added ammonia solution (50 mL) and refluxed overnight. The solvent was removed under reduced pressure, then taken into water and adjusted to pH 1 with concentrated hydrochloric acid. The aqueous mixture was washed with ethyl acetate (3×) and the pH was adjusted to pH 10 with sodium hydroxide (2 M.). The aqueous phase was extracted with chloroform (3×), dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure. Re-crystallisation from methanol/diethyl ether gave brown cubic crystals, mp 162-164 C. Yield 75%. 1H NMR (CDCl3) delta 2.15 (3H, s, CH3), 5.03 (2H, s, CH2Ph), 6.35 (1H, d, J = 6.9 Hz, 5-H), 7.25-7.31 (5H, m, CH2Ph), 7.39 (1H, d, J = 6.9 Hz, 6-H); m/z (ESI): 201.1. |
75% | With ammonium hydroxide; In ethanol; at 75℃; for 12h; | The pyrrolone (8.65 g, 40 mmol) obtained in the above reaction, 60 mL of 25% ammonia water, 50 mL of ethanol was added to a 250 mL single-mouth bottle, and heated under reflux at 75 C for 12 h.After the reaction was completed, it was cooled to room temperature, and the solvent was evaporated to give a brown oily liquid.Recrystallization from acetone/ethyl acetate gave a pale yellow solid of 2-methyl-3-benzyloxypyridone. The yield was 75%. |
64% | With ammonia; In ethanol; water; at 20℃;Heating / reflux; | A clear solution of 3-(benzyloxy)-2-methyl-4H-pyran-4-one (150 g, 0.69 mol), ethanol (300 mL) and ammonium hydroxide (28.0-30.0% solution, 690 mL, 10.5 mol) in a 2 L 3-necked round bottom flask equipped with a mechanical stirrer was heated to reflux for 5 h. The reaction mixture was allowed to cool to room temperature, and a further 230 mL of ammonium hydroxide (3.5 mol) was added. The resulting solution was heated to reflux for another 3.5 h, then allowed to cool to RT and stirred for overnight. A solid product had separated, and was collected by suction filtration. Thus, 95 g of 3-benzyloxy-2-methyl-1H-pyridin-4-one (64% yield) was obtained as a first crop. HPLC Method 4 (Example 24), RT=10.7 min, HPLC purity (peak percent area): 99% at lambda=280 nm)). 1H NMR (DMSO-d6) delta ppm: 11.3 (br s, 1H), 7.46 (s, 1H), 7.35, (m, 5H), 6.13 (s, 1H), 5.04 (s, 2H), 2.05 (s, 3H); 1H NMR (DMSO-d6+D2O) delta ppm: 7.47 (d, J=7.0 Hz, 1H), 7.39, (m, 5H), 6.20 (d, J=7.0 Hz, 1H), 5.01 (s, 2H), 2.03 (s, 3H). |
43% | With sodium hydroxide; ammonia; In ethanol; water; at 90℃; for 1h; | 2) The compound 2 (162, 2g, 750mmol) was dissolved in ethanol (-187ml), and aqueous ammonia (28%, 974ml) and a 6N aqueous sodium hydroxide solution (150ml, O00mmol) were added. After the reaction solution was stirred at 90 C for 1 hour, this was cooled to under ice-cooling, and ammonium chloride (58g, 10S0mmol) was added, To the reaction solution was added chloroform, this was extracted, and the organic layer was washed with an aqueous saturated sodium bicarbonate solution, and dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, isopropyl alcohol and diethyl ether were added to the residue, and precipitated crystals were filtered to obtain 3-benzyloxy-2-methyl- 1H-pyridine-4-one 3 (69.1g, 43%) as a pale yellow crystal.NMR (DMSO-dfi)delta: 2.05(3H, s), 5.04(2H, a), 6 14(1H, d, J=7 0Hz), 7,31-7.42(5H, m), 7 46(1H, d, J=7.2Hz), 11.29(1H, brs). |
With ammonia; In C2 H5 OH; | EXAMPLE 2 2-Methyl-3-(phenylmethoxy)-4(1H)-pyridone 62 g of product of Example 1 were dissolved in 300 ml C2 H5 OH containing 18 g NH3. The solution was kept at 110 C. for 16 hours in a glass autoclave. After cooling, the C2 H5 OH was distilled off and the crystalline residue filtered off and washed with 50 ml C2 H5 OH at 0 C.; 49.7g beige crystals were recovered M.P. =162 C. | |
With ammonia; In C2H5OH; | Example 2 2-Methyl-3-(phenylmethoxy)-4(1H)-pyridone 62g of the product of Example 1 were dissolved in 300ml C2H5OH containing 18g NH3. The solution was kept at 110C for 16 hours in a glass autoclave. After cooling, the C2H5OH was distilled off and the crystalline residue filtered off and washed with 50ml C2H5OH at 0C; 49.7g beige crystals were recovered M.P. = 162C. | |
With ammonia; In water; for 48h;Product distribution / selectivity; | The iron chelators of the invention include, but are not limited to: 2-Alkyl-N-(2'-hydroxyethoxy)methyl-3-hydroxyl-4-pyridinone chelators, which were synthesized using established methods.82 Briefly, 3-benzyloxyl-2-alkyl-4-pyridinone was synthesized as described by Dobbin et al.83 with a minor modification. First, 2-alkyl-3-hydroxyl-4-pyranone and benzylchloride were refluxed in alkaline condition to protect the 3-hydroxyl group. Then, the substitution reaction of 3-benzyloxyl-2-alkyl-4-pyranone with aqueous ammonia reacted for 48 h. 3-benzyloxyl-2-alkyl-4-pyridinone were silylated in hexamethyldisilazane under refluxing for 2 h and then alkylated using trimethylsilyl trifluoromethanesulfonate as a catalyst with benzyloxyethoxymethylchloride which could be replaced by (2-acetoxyethoxy)methyl bromide. SnCl4 could also be used as catalyst in the alkylation reaction, but resulted in separation difficulties and low yields. Both of the protection groups were removed simultaneously by hydrogenation under H2/catalyst in aqueous ethanol or by BBr3 in CH2Cl2 at 4 C. The new chelators were obtained in pure form after crystallization from a 1:1 solution of CH3Cl/MeOH. Scheme 1. R=Me (1a), Et (1b). a: benzylchloride/NaOH, then NH4OH. b: hexamethyldisilazane, chlorotrimethylsilane. c: benzyloxyethoxymethylchloride, trimethylsilyl trifluoromethanesulfonate in 1,2-dichloroethane. d: H2, Pd/C, in aqueous EtOH (or with BBr3 in CH2Cl2 at 4 C.). Characterizations have been done using proton-NMR, MS, UV-visible spectroscopy and elemental analysis. The molecular structure of chelator 1b was also confirmed by X-ray crystallography and the molecular structure is shown; Synthesis of iron chelator-nanoparticle systems: The general synthesis of the chelator 1 is described in scheme 3.86 Scheme 3. R=Me, Et. a: benzylchloride/NaOH/. b: NH4OH. C: hexamethyldisilazane/chlorotrimethylsilane/(2-acetoxyethoxy)methyl bromide, trimethylsilyl trifluoromethanesulfonate in 1,2-dichloroethane. c: basic hydrolysis with NH4OH. d: tosyl chloride in pyridine. e: nanoparticles with amino functional groups. f: BBr3/CH2Cl2 at 4 C. for 30 min. Instead of benzyloxyethoxymethylchloride, 2-acetoxyethoxy)methyl bromide is used and the synthetic method is the same as described herein. The acetyl protection group on the side chain is removed by basic hydrolysis in methanolic ammonia solution. The mixture is stirred at room temperature in a sealed flask for 24 h. After purification by silica gel chromatography using CHCl3-MeOH (8:1) as an eluent, the deprotected hydroxyl group is converted into P-toluene-sulphonyl (tosyl) ester by the reaction with tosyl chloride (1.1 moles per mole of chelator) in dry pyridine. After removal of the solvent, the crude ester is often used directly. Before conjugation, 1 mL (100 mg/mL) of amino-modified nanoparticles are washed in 10 mL of 0.1 M sodium phosphate buffer (pH 7.4). After second wash, resuspend pellet in 10 mL of tosyl activeted chelator solution, ensuring that the particles are completely suspended by vortexing. Allow to react at 37 C. for 24 hours with continuous mixing. Separate the particles conjugated with chelators by centrifugation and wash with phosphate buffered saline (pH 7.4) four times. Then, deprotect OH on pyridinone ring by BBr3 in CH2Cl2 at 4 C. with shaking for 30 min. The new chelator-particle system is obtained by centrifugation and wash four times with PBS buffer. Resuspend in 10 mL 25 mM Tris buffer (pH 7.4) and store at 4 C. until used. As mentioned above, if the nanoparticles could be damaged during the deprotective step, we will use an altered method to conjugate the chelator. The toluene sulfonic group (Tosyl-O-group) may be changed into an amino group by nucleophilic displacement reaction. To obtain primary amines in reasonable yield, sufficient excess ammonia is used. After that, first, deprotection of the OH group on the pyridinone ring by using the same deprotective method as above, then conjugate the chelator to Sulfo-NHS(N-hydroxysulfosuccinimide) preactivited carboxylic acid functinal nanoparticles just like chelators 2, 3, and DFO do. The chelator concentrations of the reaction solution before and after conjugation are determined by using UV-visible spectroscopy or HPLC, thereby the amount of the chelator conjugated to nanoparticles can be obtained by simply multiplying the difference of the concentrations with the reaction volume. | |
2.3 g | With ammonium hydroxide; In water; acetonitrile; at 80 - 90℃; for 18h;Sealed tube; | To a solution of 3-(benzyloxy)-2-methyl-4H-pyran-4-one (2.3 g) in acetonitirle (5 ml) was added aq.N in seal tube. The reaction mixture was heated at 80-90C for 18 h. After completion of reaction, the reaction mixture was cooled at RT and diluted with ethyl acetate. The organic layer was separated and further aqueous layer was extracted with 10% MeOH in DCM. The organic layer was concentrated to afford 2.3 g of desired product. 1H NMR (DMSO-d6): delta2.0 (s, 3H), 5.0 (s, 2H), 6.20 (s, 1H), 7.20- 7.40 (m, 6H), 11.20 (br s, 1H); MS [M+H]+ : 216.13. |
With ammonium hydroxide; In ethanol; water; for 12h;Reflux; | General procedure: A mixture of suitable Maltol (7.56g, 60mmol), anhydrous K2CO3 (9.12g, 66mmol), benzyl bromide (10.78g, 63mmol) and acetone (150mL) was refluxed for 8h. Once the reaction was completed, the mixture was cooled to room temperature. After the solvent was removed under reduced pressure, water (100mL) was added and the mixture was extracted four times with dichloromethane (50mL). The combined organic layer was dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure to afford intermediate 2a as yellow oil. Intermediates 2b, 2c wasprepared followed the similar procedure of 2a. 2a, 2b or 2c (4.33g, 40mmol) was then dissolved in ethanol 45mL and then 25% ammonia aqueous solution (60mL) was added, and the mixture was refluxed for 12h. Afterward, The solvent was evaporated off to obtain a pale brown solid residue, which was recrystallized from acetone/ethyl acetate, leaving the pure target compound as a pale colored solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; | 3-Benzyloxy-2-methylpyrid-4-one 3-Benzyloxy-2-methyl-4-pyrone (20 g), concentrated (s.g. 0.880) ammonia (200 ml) and ethanol (100 ml) are mixed and kept at room temperature for 3 days. The solvent and excess ammonia are then removed by rotary evaporation to yield an oil which on trituration with acetone gives 3-benzyloxy-2-methylpyrid-4-one as white crystals m.p. 162°-163° C. | |
In ethanol; | 3-Benzyloxy-2-methylpyrid-4-one 3-Benzyloxy-2-methyl-4-pyrone (20 g), concentrated (s.g. 0.880) ammonia (200 ml) and ethanol (100 ml) are mixed and kept at room temperature for 3 days. The solvent and excess ammonia are then removed by rotary evaporation to yield an oil which on trituration with acetone gives 3-benzyloxy-2-methylpyrid-4-one as white crystals m.p. 162°-163° C. |
Tags: 61049-69-2 synthesis path| 61049-69-2 SDS| 61049-69-2 COA| 61049-69-2 purity| 61049-69-2 application| 61049-69-2 NMR| 61049-69-2 COA| 61049-69-2 structure
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