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CAS No. : | 1004-36-0 | MDL No. : | MFCD00006579 |
Formula : | C7H8O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | VSYFZULSKMFUJJ-UHFFFAOYSA-N |
M.W : | 124.14 | Pubchem ID : | 13862 |
Synonyms : |
2,6-Dimethyl-gamma-pyrone
|
Num. heavy atoms : | 9 |
Num. arom. heavy atoms : | 6 |
Fraction Csp3 : | 0.29 |
Num. rotatable bonds : | 0 |
Num. H-bond acceptors : | 2.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 34.91 |
TPSA : | 30.21 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) : | -6.99 cm/s |
Log Po/w (iLOGP) : | 1.88 |
Log Po/w (XLOGP3) : | 0.1 |
Log Po/w (WLOGP) : | 1.26 |
Log Po/w (MLOGP) : | 0.13 |
Log Po/w (SILICOS-IT) : | 2.27 |
Consensus Log Po/w : | 1.13 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.17 |
Solubility : | 8.47 mg/ml ; 0.0682 mol/l |
Class : | Very soluble |
Log S (Ali) : | -0.29 |
Solubility : | 63.8 mg/ml ; 0.514 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -2.67 |
Solubility : | 0.268 mg/ml ; 0.00216 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 0.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 2.4 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H302 | 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 |
---|---|---|
72.5% | With acetic anhydride; for 2h;Reflux; | Preparation of compounds of formula (1) (R1, R2 are both H)2,6-dimethyl-4-pyrone (25 mmol, 3.1 g)withMalononitrile (250 mmol, 16.5 g)Added to 15mL of anhydrous acetic anhydride,The reaction mixture was stirred at reflux for 2h.After the reaction was completed, the reaction system was cooled to room temperature, 50 mL of boiling water was added thereto, a large amount of solid was precipitated, suction filtered, and the brown crude product was collected.The crude product was purified by silica gel column chromatography using petroleum ether / ethyl acetate (volume ratio of both: 10: 1) as eluent,The compound of formula (1) was obtained as a yellow solid,Yield 72.5%. |
60% | In acetic anhydride; for 5h;Reflux; Inert atmosphere; | 2,6-dimethyl-gamma-pyrone (12.50 g, 0.100 mol) and malononitrile (6.90 g, 0.104 mol) were dissolved in 50 mL of acetic anhydride; the solution was refluxed, under nitrogen flux, for 5 h. The system was then slowly cooled down to room temperature and the crystallization of a brown compound occurred. This compound was recovered by suction filtration and recrystallized by chloroform-hexane. Light brown needle-shape crystals were obtained. The yield was 60%. 1H NMR (CDCl3, 200 MHz); delta = 2.31 (s, 6H, -CH3); 6.53 (s, 2H, pyran CH). Mp: 192 C. |
60% | With acetic anhydride;Reflux; Inert atmosphere; | 2,6-dimethyl-g-pyrone (12.50 g, 0.100 mol) and malononitrile(6.90 g, 0.104 mol) were dissolved in 50 mL of acetic anhydride; thesolution was refluxed, under nitrogen flowing, for 5 h. The systemwas then slowly cooled down to room temperature and the crystallizationof a brown compound occurred. The compound wasrecovered by suction filtration and recrystallized by chloroformhexane.Light brown needle-shape crystals were obtained. Theyield was 60%.1H NMR (CDCl3, 200 MHz); delta 2.31 (s, 6H, -CH3); 6.53 (s, 2H,pyran CH).Mp: 192 C. |
57% | With acetic anhydride; for 1.5h;Reflux; | Example 8; Preparation of a compound having the formula:; (a) A 10.00 g sample of 2,6-dimethyl-gamma-pyrone was dissolved in 40 niL of acetic anhydride. To this solution was added 5.3 rnL of malononitrile and the mixture was heated in an oil bath for 90 min at reflux temperature. Using a distillation apparatus, the volume was reduced by one half. The brown solution was added to 600 mL warm H2O, resulting in a dark brown crystalline solid, which was collected by vacuum filtration to yield 7.901 g (57%) (NMR (CDCl3) delta 6.57 (s, 2, pyrone), 2.32 (s, 6, CH3.)) of a compound having the formula:. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; under 760.051 Torr; for 25h; | Example 9-1 2,6-Dimethyltetrahydro-4H-pyran-4-one 2,6-Dimethyl-4H-pyran-4-one (4g) was dissolved in ethanol (20mL) and 10% Pd/C (400mg) was added. The mixture was hydrogenated under H2 (latm) at room temperature for 25hrs. The catalyst was filtered through a celite pad and washed with ethanol. The filtrate was concentrated in vacuo, and the residue was purified with silica gel chromatography (hexane/ethyl acetate = 4/1) to give the target compound as a colorless oil (2. 08g). 1H-NMR (300MHz, CDC13) : 6 1. 33 (3H, d, J=6. 0Hz), 2.22 (1H, dd, J=11.4, 14.4Hz), 2.36 (1H, dd, J=2. 7,14. 4Hz), 3.74 (1H, ddq, J=2.7, 6.0, 11.4Hz). | |
5.1 g | With palladium on activated charcoal; hydrogen; In tetrahydrofuran; at 50℃; under 760.051 Torr; for 22h; | At 50 C, a solution of 2,6-dimethyl-4H-pyran-4-one (6.21 g, 50.0 mmol) in THF (93 mL) was treated with palladium on charcoal (0.53 g, 0.50 mmol). The mixture was put under H2 (1 atm), stirred for 22 h at 50 C, cooled to r.t., filtered25 (Celite) and evaporated to leave an oil (9 g). Flash chromatography (40g Si cartridge,10% TBME in petrol ether) afforded a yellow oil (5.1 g). ?H NMR (400 MHz, CDC13)oe ppm 1.30 (6H, d), 2.16 (2H, dd), 2.31 (2H, dd), 3.68 - 3.76 (2H, m). ?3C NMR (100MHz, CDC13) oe ppm 22.2 (CH3), 49.2 (CH2), 73.2 (OCH), 218.0 (CO). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | With hydrogen;palladium 10% on activated carbon; In ethanol; under 2327.23 Torr; for 8h; | A mixture of ketone 58A {13.0 g), Pd/C (10%) (1.5 g) in EtOH (80 mL) was reacted in a hydrogenation vessel under 45 psi for 8 hours. Then the mixture was filtered through Celite <n="194"/>and concentrated in vacuo. The residue was purified on a silica gel column (ISCO) with EtOAc in hexanes (0->25%) to provide 58B (8.0 g, 61% yield). |
With hydrogen;palladium 10% on activated carbon; In ethanol; under 1520.1 Torr; for 2h; | [00307] Intermediate X13 was prepared from commercially available 2,6-dimethyl-g- pyrone (Aldrich Chemical Co., Milwaukee, Wisconsin, USA). A solution of the g-pyrone was dissolved in EtOH and hydrogenated (2 atm. H2) with 10% Pd/C over 2h. The catalyst was subsequently filtered off and the solution was concentrated in vacuo to yield crude X13 which was purified by column chromatography to yield pure compound X13. 1H-NMR (CDCl3, 500 MHz): 3.72 (m, 2H), 2.35 (m, 2H), 2.21 (dd, 2H), 1.32 (d, 6H) ppm. | |
A solution of 2,6-dimethyl-4H-pyran-4-one (2 g, 16.1 mmol) in EtOH (20 mL) was stirred over Pd/C (10 wt.%, 0.2 g) under hydrogen (15 psi) for 16 hrs at ambient temperature. The suspension was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane (15 mL) and treated with Dess-Martin periodinane (2.3 g) at ambient temperature for 16 hrs. To the suspension was added saturated aqueous sodium thiosulfate solution (~3 mL) and the mixture was stirred for 1 hr. The mixture was diluted with saturated aqueous sodium bicarbonate solution (20 mL) and stirred for an additional 1 hr. The separated organic phase was washed with water and brine, dried over sodium sulfate, filtered through celite and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, EtO Ac/heptane = 10/90]. Fractions were combined and concentrated under reduced pressure providing (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-one (600 mg). GCMS: 128 [M]; Retention time = 4.25 mm. 1H NMR (400 MHz, DMSO-d6) delta [ppm]: 1.18 (d, J=6.26 Hz, 6 H) 2.11 - 2.25 (m, 4 H) 3.58 - 3.77 (m, 2 H). |
A solution of 2,6-dimethyl-4H-pyran-4-one (2 g, 16.1 mmol) in EtOH (20 rriL) was stirred over Pd/C (10 wt.%, 0.2 g) under hydrogen (15 psi) for 16 hrs at ambient temperature. The suspension was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane (15 mL) and treated with Dess-Martin periodinane (2.3 g) at ambient temperature for 16 hrs. To the suspension was added saturated aqueous sodium thiosulfate solution (~3 mL) and the mixture was stirred for 1 hr. The mixture was diluted with saturated aqueous sodium bicarbonate solution (20 mL) and stirred for an additional 1 hr. The separated organic phase was washed with water and brine, dried over sodium sulfate, filtered through celite and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, EtO Ac/heptane = 10/90]. Fractions were combined and concentrated under reduced pressure providing (2R,6S)-2,6-dimethyldihydro-2H-pyran- 4(3H)-one (600 mg). GCMS: 128 [M]; Retention time = 4.25 mm. 1H NMR (400 MHz, DMSO-d6) delta [ppm]: 1.18 (d, J=6.26 Hz, 6 H) 2.11 - 2.25 (m, 4 H) 3.58 - 3.77 (m, 2 H). | ||
A solution of 2,6-dimethyl-4H-pyran-4-one (2 g, 16.1 mmol) in EtOH (20 mL) was stirred over Pd/C (10 wt.%, 0.2 g) under hydrogen (15 psi) for 16 hrs at ambient temperature. The suspension was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane (15 mL) and treated with Dess-Martin periodinane (2.3 g) at ambient temperature for 16 hrs. To the suspension was added saturated aqueous sodium thiosulfate solution (~3 mL) and the mixture was stirred for 1 hr. The mixture was diluted with saturated aqueous sodium bicarbonate solution (20 mL) and stirred for an additional 1 hr. The separated organic phase was washed with water and brine, dried over sodium sulfate, filtered through celite and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, EtOAc/heptane = 10/90]. Fractions were combined and concentrated under reduced pressure providing (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-one (600 mg). GCMS: 128 [M]; Retention time = 4.25 min. H NMR (400 MHz, DMSO-d6) delta [ppm]: 1.18 (d, J=6.26 Hz, 6 H) 2.11 - 2.25 (m, 4 H) 3.58 - 3.77 (m, 2 H). | ||
A solution of 2,6-dimethyl-4H-pyran-4-one (2 g, 16.1 mmol) in EtOH (20 ml_) was stirred over Pd/C (10 wt.%, 0.2 g) under hydrogen (15 psi) for 16 hrs at ambient temperature. The suspension was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane (15 ml_) and treated with Dess-Martin periodinane (2.3 g) at ambient temperature for 16 hrs. To the suspension was added saturated aqueous sodium thiosulfate solution (~3 ml_) and the mixture was stirred for 1 hr. The mixture was diluted with saturated aqueous sodium bicarbonate solution (20 ml_) and stirred for an additional 1 hr. The separated organic phase was washed with water and brine, dried over sodium sulfate, filtered through celite and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, EtOAc/heptane = 10/90]. Fractions were combined and concentrated under reduced pressure providing (2R,6S)-2,6-dimethyldihydro-2H-pyran- 4(3H)-one (600 mg). GCMS: 128 [M]; Rt = 4.25 min. H NMR (400 MHz, DMSO-d6) delta [ppm]: 1.18 (d, J=6.26 Hz, 6 H) 2.1 1 - 2.25 (m, 4 H) 3.58 - 3.77 (m, 2 H). | ||
Step 1. Preparation of (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-oneA solution of 2,6-dimethyl-4H-pyran-4-one (2g, 16.1 mmol) in 20ml ethanol was stirred over 10% Pd/C (0.2g) under hydrogen (15 psi) for 16 hours at ambient temperature. TLC showed two spots; one was desired product and second one was side product in a 1 : 1 ratio. GCMS M+ 128 for product, and M+ 130 for side product.Suspension was filtered off, and the filtrate was concentrated to remove solvent to give 2.3g crude product which contained -30% of the side product. The resulting oily residue was treated with 2.3g Dess-Martin periodinane in 15ml DCM at ambient temperature for 16 hours. GCMS showed oxidation was complete, desired product formation was confirmed by GCMS at M+ 128. ~3ml NaS2C03 was added to the suspension and the resulting mixture was stirred for 1 hour at ambient temperature, then 20ml saturated sodium bicarbonate solution was added to, and new mixture was stirred for another hour. The organic phase was separated, washed with water, brine, dried and filtered through celite. The filtrate was concentrated and resulting residue was purified by ISCO eluting with 10% ethyl acetate in heptane to yield 600 mg of the desired product. GCMS: M=128. HNMR: 1.5ppm (6H), 2.3ppm (4H), 3.75ppm (2H). | ||
A solution of 2,6-dimethyl-4H-pyran-4-one (2 g, 16.1 mmol) in EtOH (20 mL) was stirred over Pd/C (10 wt.%, 0.2 g) under hydrogen (15 psi) for 16 hrs at ambient temperatu The suspension was filtered off and the filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane (15 mL) and treated with Dess-Martin periodinane (2.3 g) at ambient temperature for 16 hrs. To the suspension was added saturated aqueous sodium thiosulfate solution (~3 mL) and the mixture was stirred for 1 hr. The mixture was diluted with saturated aqueous sodium bicarbonate solution (20 mL) and stirred for an additional 1 hr. The separated organic phase was washed with water and brine, dried over sodium sulfate, filtered through celite and concentrated under reduced pressure. The residue was purified by column chromatography [silica gel, EtOAc/heptane = 10/90]. Fractions were combined and concentrated under reduced pressure providing (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-one (600 mg). GCMS: 128 [M]; Rt = 4.25 min. 1 H NMR (400 MHz, DMSO-d6) delta [ppm]: 1 .18 (d, J=6.26 Hz, 6 H) 2.1 1 - 2.25 (m, 4 H) 3.58 - 3.77 (m, 2 H). | ||
With palladium 10% on activated carbon; In tetrahydrofuran; under 2585.81 Torr; for 2h; | 2,6-Dimethyl-4H-pyran-4-one (14 g) and tetrahydrofuran (140 mL) were added to 10% Pd/C, dry (2.8 g) in a 250 mL SS pressure bottle and the mixture was stirred for 2 hours at 50 psi. The mixture was filtered through a nylon membrane and concentrated. The crude product was chromatographed on silica gel with 5-50% ethyl acetate/hexanes to afford the title compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Following the proceduredescribed by Opatz:[ 4 ]Ba(OH)2·8H2O (10.0 g, 31.7 mmol, 2.0 equiv) was dissolved almost completely in boiling water (130mL) under an argon atmosphere. The resulting suspension was added directly to a 50 C warmsolution of 2,6-dimethyl-gamma-pyrone (1.97 g, 15.9 mmol, 1.0 equiv) in aqueous NaOH solution (8 wt %, 4mL). A yellow precipitate formed immediately. The solution was cooled slowly to 0 C, the crystalswere filtered off, washed with aqueous NaOH solution (4 wt %), and then dissolved under ice coolingin aqueous HCl solution (15 wt %, 20 mL). The resulting solution was stirred for 1 h, and extractedwith Et2O. The combined organic layers were dried over anhydrous MgSO4, filtered and concentratedunder reduced pressure. The product was recrystallized from petroleum ether to afford 1b (1.35 g,60%) as a white solid. 1H NMR (300 MHz, CDCl3): delta 15.20 (s, 1H, C), 14.17 (s, 2H, B), 5.55 (s, 1H, C), 5.13 (s, 2H, B), 3.69 (s, 4H, A), 3.39 (s, 2H, C), 2.25 (s, 3H, C), 2.23 (s, 6H, A), 2.07 (s, 3H, C), 1.97 (s, 6H,B). These data are in good agreement with those reported in the literature. | |
55% | 11. Heptane-2,4,6-trione; 50.0 g 2,6-Dimethyl-gamma-pyrone are dissolved in 250 mL ethanol and treated with 50 mL of a 16 M aqueous solution of sodium hydroxide. This mixture is heated for 5 hours at 6O0C and for another 1 hour at 1000C. The residue is filtered off and washed with diethylether. This residue is now dissolved in water and put in 500 mL of a 3 M aqueous solution of hydrochloric acid. The aqueous phase is <n="75"/>extracted with diethylether. The combined organic phase is dried over sodium sulfate and the solvent is evaporated in vacuo. This yields 31.6 g (55%) of the title compound. M. p. 43-45 0C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With palladium 10% on activated carbon; hydrogen; In ethanol; at 35℃; under 2585.81 Torr; for 17h; | The solution of compound cap 2a (73 g, 0.59 mol) in ethanol was added Pd/C (10%, 40 g) and the reaction was stirred at 35C under an H2 (50 Psi) for 17 hours. The reaction was filtered through celite and the volatiles were removed in vacuo to provide compound cap 2b (76 g, 99% yield). 1H-NMR: (CDC13) delta: 3.75 (s, 1 H), 3.44-3.40 (m, 2 H), 1.88 (d, / = 16 Hz, 2 H), 1.19 (d, / = 8 Hz, 6 H), 1.14-1.08 (m, 2 H) |
99% | With palladium 10% on activated carbon; hydrogen; In ethanol; at 35℃; under 2585.81 Torr; for 17h; | The solution of compound cap 4a (73 g, 0.59 mol) in ethanol was added Pd/C (10%, 4 g) and the reaction was allowed to stir at 35 C under H2 (50 Psi) for 17 hours. The reaction was filtered through CELITE and the volatiles were removed in vacuo to provide cap 4b (76 g, 99% yield). 1H NMR: (CDC13) delta: 3.75 (s, 1 H), 3.44-3.40 (m, 2 H), 1.88 (d, / = 16 Hz, 2 H), 1.19 (d, / = 8 Hz, 6 H), 1.14-1.08 (m, 2 H). |
10% | With palladium 10% on activated carbon; hydrogen; In methanol; at 20℃; under 760.051 Torr; for 24h; | To a solution of 2,6-dimethyl-y-pyrone (1.5 g, 12.1mmol) in MeOH (15 mL) was added 10% Pd/C (150.8 mg) at rt and treated with H2 (1 atm) for 24 h. After reaction completion the mixture was filtered through a Celite pad and washed with MeOH and the filtrate was concentrated under reduced pressure to give a pale yellow oil. Purification by flash chromatography using ELSD detector (Biotage Isolera, 50 g HP-SIL, 0-100 % Et20 in hexane) gave the title compound as a pale yellow oil (151 mg, 10 %). ? NMR (400 MHz, CDCl3) delta ppm 3.74-3.81 (m, 1 H), 3.45-3.49 (m, 2 H), 1.90-1.94 (m, 2 H), 1.70 (br. s, 1 H), 1.50 (br. s, 1 H), 1.22 (d, J=6.4 Hz, 6 H) |
With palladium 10% on activated carbon; hydrogen; In methanol; at 50℃; under 2585.81 Torr; for 24h; | A mixture of 2,6-dimethyl-4H-pyran-4-one (50 g, 0.4 mol) and 10% Pd/C (25 g, 24 mmol) in methanol (400 mL) was stirred under 50 psi of at 50 C for 24 h. The catalyst was removed by filtration and the filtrate solvent was removed in vacuo to give the title compound. 1 H NMR delta 3.82 - 3.89 (m, 1 H), 3.67 - 3.74 (m, 1 H), 3.36 - 3.43 (m, 2 H), 1.83 - 1.87 (dd, 2 H), 1.54-1.59 (m, 1 H), 1.29 - 1.39 (m, 1H), 1.16-1.17 (d, 6 H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With acetic anhydride |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
68% | In acetic anhydride; for 5h;Reflux; Inert atmosphere; | General procedure: 2,6-dimethyl-gamma-pyrone (12.50 g, 0.100 mol) and malononitrile (6.90 g, 0.104 mol) were dissolved in 50 mL of acetic anhydride; the solution was refluxed, under nitrogen flux, for 5 h. The system was then slowly cooled down to room temperature and the crystallization of a brown compound occurred. This compound was recovered by suction filtration and recrystallized by chloroform-hexane. Light brown needle-shape crystals were obtained. The yield was 60%. |
68% | With acetic anhydride;Reflux; Inert atmosphere; | General procedure: 2,6-dimethyl-g-pyrone (12.50 g, 0.100 mol) and malononitrile(6.90 g, 0.104 mol) were dissolved in 50 mL of acetic anhydride; thesolution was refluxed, under nitrogen flowing, for 5 h. The systemwas then slowly cooled down to room temperature and the crystallizationof a brown compound occurred. The compound wasrecovered by suction filtration and recrystallized by chloroformhexane.Light brown needle-shape crystals were obtained. Theyield was 60%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | With hydrogen;palladium 10% on activated carbon; In methanol; under 19001.3 Torr; for 24h; | 10 g of 2, 6-dimethyl-gamma-pyrone are dissolved in 200 ml of methanol and then 0.8 g of palladium-on- charcoal at 10% is added. The reaction mixture is stirred for 24 hours under 25 atmospheres of hydrogen. The medium is filtered and then the solvent is evaporated off. 8.81 g of cis-2, 6-dimethyltetrahydro- pyran-4-one are recovered. Yield = 88%. |
With hydrogen;palladium on carbon; In ethanol; under 2585.81 Torr; | Synthesis of (2R)-3-(2-amino-6-o-tolylquinolin-3-yl)-N-(cis-2,6-dimethyltetrahydro- 2H-pyran-4-yl)-2-methylpropanamide; Stepl :; A solution of 2,6-dimethyl-4-pyrone (5.0 g, 40.3 mmol) in ethanol was charged with Pd/C (0.86 g, 0.40 mmol). The mixture was subjected to pressurized H2 conditions using a parr hydrogenator (50 psi) and the mixture was shaken overnight. Afterwards, the mixture was filtered through a pad of celite, and the filtrate was concentrated. The crude material was purified by column chromatography using 5% to 60% EtOAc-hexanes eluent. The desired fractions were combined and concentrated to give cis-2,6- dimethyldihydro-2//-pyran-4(3//)-one as a colorless oil. | |
With 5%-palladium/activated carbon; hydrogen; In ethanol; under 2068.65 Torr; for 24h;Inert atmosphere; | Preparative Example 5.4 czs-2,6-Dimethyltetrahydro-4H-pyran-4-on 2,6-Dimethyl-4H-pyran-4-one (2.0 g, 16 mmol) was dissolved in ethanol (10 niL) and purged under nitrogen. Palladium on carbon (5%, 200 mg) was then added and the reaction mixture stirred under hydrogen gas (40 psi) for 24 hours. The reaction mixture was filtered over CELITE, rinsed with ethanol, and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (5 to 30% EtOAc/hexanes) to afford cis-2,6- dimethyltetrahydro-4H-pyran-4-one as a colorless liquid. XH NMR (500 MHz, CDC13) delta 3.77- 3.70 (m, 2H), 2.38-2.32 (m, 2H), 2.25-2.20 (m, 2H), 1.32 (d, J = 6.1 Hz, 6H). |
With hydrogen;palladium 10% on activated carbon; In ethanol; under 1520.1 Torr; for 2h; | [0343] Intermediate X13 was prepared from commercially available 2,6-dimethyl-g- pyrone (Aldrich Chemical Co., Milwaukee, Wisconsin, USA). A solution of the g-pyrone was dissolved in EtOH and hydrogenated (2 atm. H2) with 10% Pd/C over 2h. The catalyst was subsequently filtered off and the solution was concentrated in vacuo to yield crude X13 which was purified by "column chromatography to yield pure compound X13. 1H-NMR (CDCl3, 500 MHz): 3.72 (m, 2H), 2.35 (m, 2H), 2.21 (dd, 2H), 1.32 (d, 6H) ppm. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; under 775.743 Torr; for 16h; | Step 1. Preparation of (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-one; A solution of 2,6-dimethyl-4H-pyran-4-one (2 g, 16.1 mmol) in 20 ml ethanol was stirred over 10% Pd/C (0.2 g) under hydrogen (15 psi) for 16 hours at ambient temperature. TLC showed two spots; one was desired product and second one was side product in a 1:1 ratio. GCMS M+ 128 for product, and M+ 130 for side product.Suspension was filtered off, and the filtrate was concentrated to remove solvent to give 2.3 g crude product which contained 30%> of the side product. The resulting oily residue was treated with 2.3 g Dess-Martin periodinane in 15 ml DCM at ambient temperature for 16 hours. GCMS showed oxidation was complete, desired product formation was confirmed by GCMS at M+ 128. 3 ml NaS2CO3 was added to the suspension and the resulting mixture was stirred for 1 hour at ambient temperature, then 20 ml saturated sodium bicarbonate solution was added to, and new mixture was stirred for another hour. The organic phase was separated, washed with water, brine, dried and filtered through celite. The filtrate was concentrated and resulting residue was purified by ISCO eluting with 10% ethyl acetate in heptane to yield 600 mg of the desired product. GCMS: M=128. HNMR: 1.5 ppm (6H), 2.3 ppm (4H), 3.75 ppm (2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen;palladium on carbon; In ethanol; at 20℃; under 3620.13 Torr; for 12h; | C - 179, Step a[00310] 2,6-Dimethyl-4H-pyran-4-one (10 g, 81 mmol) was dissolved in ethanol (125 niL) and Pd/C (1 g, 0.94 mmol) was added. The mixture was hydrogenated in a Pan- shaker under ¾ (0.325 g, 161 mmol) (70 psi) at room temperature for 12 hrs. The catalyst was filtered through a pad of CELITE and washed with ethanol. The filtrate was concentrated in vacuum and he residue was purified via BIOTAGE (2% to 25 % EtO Ac/Hex; 160g column). Two fractions of clear oils were isolated. The first eluting one corresponded to (2R,6S)-2,6-dimethyldihydro-2H-pyran-4(3H)-one (1.8 g) while the second one corresponded to Cap- 179, Step a (1.8 g).[00311] (2R,6S)-2,6-Dimethyldihydro-2H-pyran-4(3H)-one data: XH NMR (500 MHz, CDC13) delta ppm 3.69 (2 H, ddd, J=11.29, 5.95, 2.29 Hz), 2.24 - 2.36 (2 H, m), 2.08 - 2.23 (2 H, m), 1.18 - 1.34 (6 H, m); 13C NMR (126 MHz, CDC13) delta ppm 206.96 (1 C, br. s.), 72.69 (2 C, s), 48.70 (2 C, s), 21.72 (2 C, s).[00312] Cap-179, Step a data: ¾ NMR (500 MHz, CDC13) delta ppm 3.69 - 3.78 (1 H, m), 3.36 - 3.47 (2 H, m), 2.10 (1 H, br. s.), 1.88 (2 H, dd, J=12.05, 4.73 Hz), 1.19 (6 H, d, J=6.10 Hz), 1.10 (2 H, q, J=10.70 Hz); 13C NMR (126 MHz, CDC13) delta ppm 71.44 (2 C, s), 67.92 (1 C, s), 42.59 (2 C, s), 21.71 (2 C, s). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | In methanol for 1h; Reflux; | 1. General procedure for preparation of pyrylium sulfanates General procedure: 0.03 mole of sulfonic acid was dissolved in 50 mL methanol and equimolar amount of 4-pyrone soluble in methanol was added. The mixture was stirring and heating at boiling point of methanol using reflexive condenser for 1h. Methanol was removed under reduced pressure (60 °C, 30×102 Pa). The obtained liquid product was shaken with 20 mL diethyl ether and dried out under vacuum for 3 hours or obtained solid product was crystallized from the mixture of methanol/toluene, 1:5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; under 3620.13 Torr; for 72h; | C -179, step a2,6-Dimethyl-4H-pyran-4-one (15 g, 121 mmol) was dissolved in ethanol (300 mL) and 10 % Pd/C (1.28 g, 1.21 mmol) was added. The mixture was hydrogenated in a Parr shaker under ¾ (70 psi) at room temperature for 72 hrs. The reaction mixture was filtered through a pad of diatomaceous earth (Celite ) and washed with ethanol. The filtrate was concentrated in vacuum and the residue was purified via flash chormatography (10% to 30 % EtO Ac/Hex). Two fractions of clear oils were isolated. The first eluting fractions were a mixture of (2R,4r,6S)-2,6- dimethyltetrahydro-2H-pyran-4-ol (Cap-1, step a) and (2R,4s,6S)-2,6- dimethyltetrahydro-2H-pyran-4-ol (1.2 g) while the latter eluting fractions corresponded to only Cap-179, step a (10.73 g). XH NMR (500 MHz, CDC13) delta ppm 3.69 - 3.78 (1 H, m), 3.36 - 3.47 (2 H, m), 2.10 (1 H, br. s.), 1.88 (2 H, dd, J=12.05, 4.73 Hz), 1.19 (6 H, d, J=6.10 Hz), 1.10 (2 H, q, J=10.70 Hz). 13C NMR (126 MHz, CDC13) delta ppm 71.44 (2 C), 67.92 (1 C), 42.59 (2 C), 21.71 (2 C). | |
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; under 3620.13 Torr; for 72h; | 2,6-Dimethyl-4H-pyran-4-one (15 g, 121 mmol) was dissolved in ethanol(300 mL) and 10 % Pd/C (1.28 g, 1.21 mmol) was added. The mixture was hydrogenated in a Parr shaker under ¾ (70 psi) at room temperature for 72 hrs. The reaction mixture was filtered through a pad of diatomaceous earth (Celite ) and washed with ethanol. The filtrate was concentrated in vacuum and the residue was purified via flash chormatography (10% to 30 % EtO Ac/Hex). Two fractions of clear oils were isolated. The first eluting fractions were a mixture of (2R,4r,6S)-2,6- dimethyltetrahydro-2H-pyran-4-ol (Cap-1, step a) and (2R,4s,6S)-2,6- dimethyltetrahydro-2H-pyran-4-ol (1.2 g) while the latter eluting fractions corresponded to only Cap-1, step a (10.73 g). 1H NMR (500 MHz, CDC13) delta ppm 3.69 - 3.78 (1 H, m), 3.36 - 3.47 (2 H, m), 2.10 (1 H, br. s.), 1.88 (2 H, dd, J=12.05, 4.73 Hz), 1.19 (6 H, d, .7=6.10 Hz), 1.10 (2 H, q, J=10.70 Hz). 13C MR (126 MHz, CDC13) delta ppm 71.44 (2 C), 67.92 (1 C), 42.59 (2 C), 21.71 (2 C). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With palladium 10% on activated carbon; hydrogen; In ethanol; at 35℃; under 2585.81 Torr; for 17h; | The solution of compound cap 2a (73 g, 0.59 mol) in ethanol was added Pd/C (10%, 40 g) and the reaction was stirred at 35C under an H2 (50 Psi) for 17 hours. The reaction was filtered through celite and the volatiles were removed in vacuo to provide compound cap 2b (76 g, 99% yield). 1H-NMR: (CDC13) delta: 3.75 (s, 1 H), 3.44-3.40 (m, 2 H), 1.88 (d, J= 16 Hz, 2 H), 1.19 (d, J= 8 Hz, 6 H), 1.14-1.08 (m, 2 H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With sodium ethanolate; In ethanol; at 25 - 40℃; for 48h; | General procedure: 2,6-dimethyl-4-pyrone (0.31g, 2.50mmol) and B-n (6.25mmol) were dissolved in ethyl alcohol (20mL). Sodium ethoxide (0.43g, 6.25mmol) in ethyl alcohol (10mL) was added dropwise to the above solution. After stirring at 25-40C for 2 days, 5% hydrochloric acid was employed to adjust the pH of the mixture to 7. The mixture was then extracted with dichloromethane (3×20mL), the organic phases were washed with brine (3×50mL), dried over anhydrous Na2SO4, concentrated to afford the crude product. It was purified by column chromatography (petroleum ether/ethyl acetate) and recrystallized in ethyl alcohol to afford the target compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With sodium ethanolate; In ethanol; at 25 - 40℃; for 48h; | General procedure: 2,6-dimethyl-4-pyrone (0.31g, 2.50mmol) and B-n (6.25mmol) were dissolved in ethyl alcohol (20mL). Sodium ethoxide (0.43g, 6.25mmol) in ethyl alcohol (10mL) was added dropwise to the above solution. After stirring at 25-40C for 2 days, 5% hydrochloric acid was employed to adjust the pH of the mixture to 7. The mixture was then extracted with dichloromethane (3×20mL), the organic phases were washed with brine (3×50mL), dried over anhydrous Na2SO4, concentrated to afford the crude product. It was purified by column chromatography (petroleum ether/ethyl acetate) and recrystallized in ethyl alcohol to afford the target compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With sodium ethanolate; In ethanol; at 25 - 40℃; for 48h; | General procedure: 2,6-dimethyl-4-pyrone (0.31g, 2.50mmol) and B-n (6.25mmol) were dissolved in ethyl alcohol (20mL). Sodium ethoxide (0.43g, 6.25mmol) in ethyl alcohol (10mL) was added dropwise to the above solution. After stirring at 25-40C for 2 days, 5% hydrochloric acid was employed to adjust the pH of the mixture to 7. The mixture was then extracted with dichloromethane (3×20mL), the organic phases were washed with brine (3×50mL), dried over anhydrous Na2SO4, concentrated to afford the crude product. It was purified by column chromatography (petroleum ether/ethyl acetate) and recrystallized in ethyl alcohol to afford the target compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With sodium ethanolate; In ethanol; at 25 - 40℃; for 48h; | General procedure: 2,6-dimethyl-4-pyrone (0.31g, 2.50mmol) and B-n (6.25mmol) were dissolved in ethyl alcohol (20mL). Sodium ethoxide (0.43g, 6.25mmol) in ethyl alcohol (10mL) was added dropwise to the above solution. After stirring at 25-40C for 2 days, 5% hydrochloric acid was employed to adjust the pH of the mixture to 7. The mixture was then extracted with dichloromethane (3×20mL), the organic phases were washed with brine (3×50mL), dried over anhydrous Na2SO4, concentrated to afford the crude product. It was purified by column chromatography (petroleum ether/ethyl acetate) and recrystallized in ethyl alcohol to afford the target compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With sodium ethanolate; In ethanol; at 25 - 40℃; for 48h; | General procedure: 2,6-dimethyl-4-pyrone (0.31g, 2.50mmol) and B-n (6.25mmol) were dissolved in ethyl alcohol (20mL). Sodium ethoxide (0.43g, 6.25mmol) in ethyl alcohol (10mL) was added dropwise to the above solution. After stirring at 25-40C for 2 days, 5% hydrochloric acid was employed to adjust the pH of the mixture to 7. The mixture was then extracted with dichloromethane (3×20mL), the organic phases were washed with brine (3×50mL), dried over anhydrous Na2SO4, concentrated to afford the crude product. It was purified by column chromatography (petroleum ether/ethyl acetate) and recrystallized in ethyl alcohol to afford the target compound.2.3.1 2,6-bis((E)-4-butoxystyryl)-4H-pyran-4-one (PASP-4) (0009) Yellow solid (0.74g), 67% yield, m.p. 187-188C. IR (KBr, cm-1): 3040, 2930, 2876, 1643, 1615, 1509, 1391, 1245, 1182, 963, 745. 1H NMR (CDCl3, 400MHz) delta (ppm): 7.54 (d, J=8.4Hz, 4H), 7.46 (d, J=16.0Hz, 2H), 6.97 (d, J=8.8Hz, 4H), 6.64 (d, J=16.0Hz, 2H), 6.24 (s, 2H), 4.05 (t, J=12.8Hz, 4H), 1.85-1.78 (m, 4H), 1.58-1.49 (m, 4H), 1.04 (t, J=14.8Hz, 6H). 13C NMR (CDCl3, 100MHz) delta (ppm): 180.40, 161.39, 160.62, 135.55, 129.09, 127.56, 117.48, 114.96, 113.17, 67.89, 31.24, 19.23, 13.83. HRMS (ESI): calcd for C29H32O4: 467.2193 (M+Na)+, found 467.2195. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With sodium ethanolate; In ethanol; at 25 - 40℃; for 48h; | General procedure: 2,6-dimethyl-4-pyrone (0.31g, 2.50mmol) and B-n (6.25mmol) were dissolved in ethyl alcohol (20mL). Sodium ethoxide (0.43g, 6.25mmol) in ethyl alcohol (10mL) was added dropwise to the above solution. After stirring at 25-40C for 2 days, 5% hydrochloric acid was employed to adjust the pH of the mixture to 7. The mixture was then extracted with dichloromethane (3×20mL), the organic phases were washed with brine (3×50mL), dried over anhydrous Na2SO4, concentrated to afford the crude product. It was purified by column chromatography (petroleum ether/ethyl acetate) and recrystallized in ethyl alcohol to afford the target compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | With sodium ethanolate; In ethanol; at 25 - 40℃; for 48h; | General procedure: 2,6-dimethyl-4-pyrone (0.31g, 2.50mmol) and B-n (6.25mmol) were dissolved in ethyl alcohol (20mL). Sodium ethoxide (0.43g, 6.25mmol) in ethyl alcohol (10mL) was added dropwise to the above solution. After stirring at 25-40C for 2 days, 5% hydrochloric acid was employed to adjust the pH of the mixture to 7. The mixture was then extracted with dichloromethane (3×20mL), the organic phases were washed with brine (3×50mL), dried over anhydrous Na2SO4, concentrated to afford the crude product. It was purified by column chromatography (petroleum ether/ethyl acetate) and recrystallized in ethyl alcohol to afford the target compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With sodium ethanolate; In ethanol; at 25 - 40℃; for 48h; | General procedure: 2,6-dimethyl-4-pyrone (0.31g, 2.50mmol) and B-n (6.25mmol) were dissolved in ethyl alcohol (20mL). Sodium ethoxide (0.43g, 6.25mmol) in ethyl alcohol (10mL) was added dropwise to the above solution. After stirring at 25-40C for 2 days, 5% hydrochloric acid was employed to adjust the pH of the mixture to 7. The mixture was then extracted with dichloromethane (3×20mL), the organic phases were washed with brine (3×50mL), dried over anhydrous Na2SO4, concentrated to afford the crude product. It was purified by column chromatography (petroleum ether/ethyl acetate) and recrystallized in ethyl alcohol to afford the target compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With sodium ethanolate; In ethanol; at 25 - 40℃; for 48h; | General procedure: 2,6-dimethyl-4-pyrone (0.31g, 2.50mmol) and B-n (6.25mmol) were dissolved in ethyl alcohol (20mL). Sodium ethoxide (0.43g, 6.25mmol) in ethyl alcohol (10mL) was added dropwise to the above solution. After stirring at 25-40C for 2 days, 5% hydrochloric acid was employed to adjust the pH of the mixture to 7. The mixture was then extracted with dichloromethane (3×20mL), the organic phases were washed with brine (3×50mL), dried over anhydrous Na2SO4, concentrated to afford the crude product. It was purified by column chromatography (petroleum ether/ethyl acetate) and recrystallized in ethyl alcohol to afford the target compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With sodium ethanolate; In ethanol; at 25 - 40℃; for 48h; | General procedure: 2,6-dimethyl-4-pyrone (0.31g, 2.50mmol) and B-n (6.25mmol) were dissolved in ethyl alcohol (20mL). Sodium ethoxide (0.43g, 6.25mmol) in ethyl alcohol (10mL) was added dropwise to the above solution. After stirring at 25-40C for 2 days, 5% hydrochloric acid was employed to adjust the pH of the mixture to 7. The mixture was then extracted with dichloromethane (3×20mL), the organic phases were washed with brine (3×50mL), dried over anhydrous Na2SO4, concentrated to afford the crude product. It was purified by column chromatography (petroleum ether/ethyl acetate) and recrystallized in ethyl alcohol to afford the target compound. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | With sodium ethanolate; In ethanol; at 20℃; for 24h;Inert atmosphere; | General procedure: To a stirred solution of sodium ethoxide prepared from sodium (1.1 g, 22.5 mmol) in ethanol (40 mL) ware added, under inert atmosphere,a solution of pyran-4-one 1 (R = Me) (2.5 g, 20 mmol) in ethanol (40 mL) and then the aldehyde 11 (40 mmol) at a rate that ensured a temperature under 20 C. The reaction mixture was stirred at room temperature for 8 h and is let to stay 16 h when a yellow material precipitates from the solution. This precipitate is filtered on a funnel and was purified by column chromatographyusing silica gel and DCM as eluent and then DCM and AcOEt in increasing amounts. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | With sodium ethanolate; In ethanol; at 20℃; for 24h;Inert atmosphere; | General procedure: To a stirred solution of sodium ethoxide prepared from sodium (1.1 g, 22.5 mmol) in ethanol (40 mL) ware added, under inert atmosphere,a solution of pyran-4-one 1 (R = Me) (2.5 g, 20 mmol) in ethanol (40 mL) and then the aldehyde 11 (40 mmol) at a rate that ensured a temperature under 20 C. The reaction mixture was stirred at room temperature for 8 h and is let to stay 16 h when a yellow material precipitates from the solution. This precipitate is filtered on a funnel and was purified by column chromatographyusing silica gel and DCM as eluent and then DCM and AcOEt in increasing amounts. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With sodium ethanolate; In ethanol; at 20℃; for 24h;Inert atmosphere; | General procedure: To a stirred solution of sodium ethoxide prepared from sodium (1.1 g, 22.5 mmol) in ethanol (40 mL) ware added, under inert atmosphere,a solution of pyran-4-one 1 (R = Me) (2.5 g, 20 mmol) in ethanol (40 mL) and then the aldehyde 11 (40 mmol) at a rate that ensured a temperature under 20 C. The reaction mixture was stirred at room temperature for 8 h and is let to stay 16 h when a yellow material precipitates from the solution. This precipitate is filtered on a funnel and was purified by column chromatographyusing silica gel and DCM as eluent and then DCM and AcOEt in increasing amounts. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86% | With piperidine; In acetonitrile; for 24h;Reflux; Inert atmosphere; | General procedure: A solution of 4H-pyran derivative (1, 3a and 3b) (1.20 mmol),ferrocenecarboxaldehyde (2.40 mmol), and piperidine (1 mL) in dryacetonitrile (10 mL) was refluxed for 24 h under argon atmosphere.The reaction was controlled with TLC method by monitoring theferrocenecarboxaldehyde in the solution of reaction. After the completionof the reaction, the solution was cooled to room temperature andthe product purified using column chromatography over silica gel andEtOAc as eluent. Further purificationwas performed by recrystallizationfrom hexane: EtOAc (8:2) to give the corresponding compound as apure solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | [00137] (±)-l-(5-Methyl-lH-pyrazol-3-yl)propan-2-amine Dihydrochloride (7). Prepared through a modification of a reported procedure (12): To 2,6-dimethyl-4-pyrone (2.50 g, 20.1 mmol) in methanol (6 mL) in a room temperature water bath (to control a minor exothermic event) was added with stirring hydrazine hydrate (19.4 mg, 60.4 mmol). The solution was stirred at rt for 40 h, at which point acetic acid (8 mL) was added. The mixture was then hydrogenated over platinum oxide hydrate (375 mg) at 60 C while maintaining a pressure between 50 and 100 psi. After 5 h, the mixture was cooled to rt and filtered through Celite. The filter cake was rinsed with ethanol. The filtrate was concentrated to a thin oil under reduced pressure. The oil was basified to a pH of 11-12 via the slow addition of 5 N KOH. The resultant solution was then extracted with an equal volume of 2-butanol (4x), and the combined extracts were stirred with solid NaCl for 20 min to draw out water. The resultant brine layer was discarded, and the organic layer was concentrated to afford a viscous oil. This was dissolved in 100 mL of toluene, and the solution was concentrated under vacuum at 60 C to afford a viscous oil containing some white solids. The oil was dissolved in DCM and filtered through a generous wad of cotton to complete the drying process. The resultant pale-yellow solution was concentrated once again to afford a constant mass of 3.79 g (89%) of the free base amine as a viscous syrup. The material was dissolved in 20 mL of methanol and cooled in an ice bath. Concentrated HC1 (5 mL, ~60 mmol) was added, and the solvent was removed under vacuum. The resultant oil was dissolved in 100 mL of methanol and again concentrated to an oil. This was then dissolved in 25 mL of methanol and with stirring was diluted with 100 mL of ethyl acetate. Continued stirring afforded a white precipitate. After stirring overnight, the solid was collected via filtration and rinsed with 1 :9 methanol/ethyl acetate followed by ethyl ether. Drying under a stream of air afforded 2.84 g (67%) of the title compound as a white solid: mp 187.9-189.5 C. NMR (400 MHz, CD3OD) d 6.56 (s, 1H), 3.70 (m, 1H), 3.20 (dd, J = 5.9, 14.8 Hz, 1H), 3.04 (dd, J = 8.6, 14.8 Hz, 1H), 2.46 (s, 3H), 1.34 (d, J = 6.6 Hz, 3H). MS m/z (ion) 140 (M + H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sodium methylate; In methanol; at 20℃; for 24h;Inert atmosphere; | To a magnetically stirred mixture of 4-fluorobenzaldehyde 1(4 mmol) and 2,6-dimethyl-4H-pyran-4-one 2 (2 mmol) in 3mL of dry MeOH, NaOMe (4 mmol) was slowly added undergentle stirring and allowed to react for 24 h at room temperature.The product was obtained as a precipitate, which was collected by filtration and washed with cold MeOH. The solid was then recrystallized with MeOH to give 3 without byproducts. light brown. Yield: 80%; m.p.oC 290-295; IR(KBr, cm-1) upsilon: 1615 (C=O), 1564 (C=C), 848 (C-F). 1HNMR(400 MHz, CDCl3): delta= 6.27 (s, 2H, CH), 6.64-6.68(dd, 2H, =CH), 7.10-7.14 (m, 4H, Aromatic), 7.40- 7.44 (dd,2H, =CH), 7.54-7.58 (m, 4H, Aromatic). 13C-NMR (100MHz, CDCl3): delta= 115.99, 118.49, 128.19, 129.99, 133.35,159.91, 163.61, 179.04. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
76.7% | With sodium methylate; In methanol; at 25℃; for 24h; | 3.96 g (11 mmol) of intermediate ma-2 and 0.62 g (5 mmol) of 2,6-dimethylpyranone and 0.42 g (11 mmol) of fresh sodium methoxide in 30 ml of methanol were reacted at 25 C for 24 h. Completion of the reaction, cooled to room temperature, adjusted to neutral acid, dichloromethane (30ml) and extracted three times, washed with water, the organic phase dried over anhydrous MgSO4, and rotary evaporated to remove the solvent. Column chromatography to give the final desired product La-2, a yield of 76.7%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63.4% | With sodium methylate; In methanol; at 25℃; for 24h; | 4.27 g (11 mmol) of intermediate ma-4 and 2,6-dimethylpyranone 0.62 g (5 mmol) and 0.42 g (11 mmol) of fresh sodium methoxide in 30 ml of methanol were reacted at 25 C for 24 h. Completion of the reaction, cooled to room temperature, adjusted to neutral acid, dichloromethane (30ml) and extracted three times, washed with water, the organic phase dried over anhydrous MgSO4, and rotary evaporated to remove the solvent. Column chromatography to give the final desired product La-4, 63.4% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
57.3% | With sodium methylate; In methanol; at 35℃; for 24h; | 4.58 g (11 mmol) of intermediate ma-6 and 0.66 g (5 mmol) of 2,6-dimethylpyranone and 0.42 g (11 mmol) of fresh sodium methoxide were reacted in 30 ml of methanol at 35 C for 24 h. Completion of the reaction, cooled to room temperature, adjusted to neutral acid, dichloromethane (30ml) and extracted three times, washed with water, the organic phase dried over anhydrous MgSO4, and rotary evaporated to remove the solvent. Column chromatography to give the final target product La-6, a yield of 57.3%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
52.4% | With sodium methylate; In methanol; at 35℃; for 24h; | 4.88 g (11 mmol) of intermediate ma-8 and 0.66 g (5 mmol) of <strong>[1004-36-0]2,6-dimethylpyrone</strong> and 0.76 g (11 mmol) of fresh sodium ethoxide were reacted in 30 ml of ethanol at 35 C for 24 h. Completion of the reaction, cooled to room temperature, adjusted to neutral acid, dichloromethane (30ml) and extracted three times, washed with water, the organic phase dried over anhydrous MgSO4, and rotary evaporated to remove the solvent. Column chromatography to give the final desired product La-8, a yield of 52.4%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
47.3% | With sodium ethanolate; In ethanol; at 40℃; for 24h; | 5.19 g (11 mmol) of intermediate ma-10 and 0.66 g (5 mmol) of <strong>[1004-36-0]2,6-dimethylpyrone</strong> and 0.76 g (11 mmol) of fresh sodium ethoxide were reacted in 30 ml of ethanol at 40 C for 24 hours. After the reaction was completed, the mixture was cooled to EtOAc. Column chromatography was carried out to obtain the final target product La-10, yield 47.3%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
74.5% | With sodium methylate; In methanol; at 25℃; for 24h; | 4.81 g (11 mmol) of intermediate mb-2 and 0.62 g (5 mmol) of 2,6-dimethylpyranone and 0.42 g (11 mmol) of fresh sodium methoxide in 30 ml of methanol were reacted at 25 C for 24 h. Completion of the reaction, cooled to room temperature, adjusted to neutral acid, dichloromethane (30ml) and extracted three times, washed with water, the organic phase dried over anhydrous MgSO4, and rotary evaporated to remove the solvent. Column chromatography to give the final desired product Lb-2, a yield of 74.5%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60.1% | With sodium methylate; In methanol; at 25℃; for 24h; | 5.12 g (11 mmol) of intermediate mb-4 and 2,6-dimethylpyranone 0.62 g (5 mmol) and 0.42 g (11 mmol) of fresh sodium methoxide in 30 ml of methanol were reacted at 25 C for 24 h. Completion of the reaction, cooled to room temperature, adjusted to neutral acid, dichloromethane (30ml) and extracted three times, washed with water, the organic phase dried over anhydrous MgSO4, and rotary evaporated to remove the solvent. Column chromatography to give the final desired product Lb-4, a yield of 60.1%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55.9% | With sodium methylate; In methanol; at 35℃; for 24h; | 5.42 g (11 mmol) of intermediate mb-6 and 2,6-dimethylpyranone 0.62 g (5 mmol) and 0.42 g (11 mmol) of fresh sodium methoxide in 30 ml of methanol were reacted at 35 C for 24 h. Completion of the reaction, cooled to room temperature, adjusted to neutral acid, dichloromethane (30ml) and extracted three times, washed with water, the organic phase dried over anhydrous MgSO4, and rotary evaporated to remove the solvent. Column chromatography to give the final target product Lb-6, a yield of 55.9%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
49.6% | With sodium ethanolate; In ethanol; at 35℃; for 24h; | 5.73 g (11 mmol) of intermediate mb-8 and <strong>[1004-36-0]2,6-dimethylpyrone</strong> 0.62 g (5 mmol) and 0.76 g (11 mmol) of fresh sodium ethoxide were reacted in 30 ml of ethanol at 35 C for 24 h. After completion of the reaction, the mixture was cooled to room temperature, acidified to neutral, extracted with dichloromethane (30 ml), washed with water, and the organic phase was dried over anhydrous MgSO4, Column chromatography was carried out to obtain the final target product Lb-8, yield 49.6%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66.9% | With sodium methylate; In methanol; at 25℃; for 24h; | 6.77 g (11 mmol) of intermediate mc-2 and 2,6-dimethylpyranone 0.62 g (5 mmol) and 0.42 g (11 mmol) of fresh sodium methoxide in 30 ml of methanol were reacted at 25 C for 24 h. After completion of the reaction, the mixture was cooled to room temperature, acidified to neutral, extracted with dichloromethane (30 ml), washed with water, and the organic phase was dried over anhydrous MgSO4. Column chromatography was carried out to obtain the final target product Lc-2, yield 66.9%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56.9% | With sodium methylate; In methanol; at 25℃; for 24h; | 7.07 g (11 mmol) of intermediate mc-4 and 2,6-dimethylpyranone 0.62 g (5 mmol) and 0.42 g (11 mmol) of fresh sodium methoxide in 30 ml of methanol were reacted at 25 C for 24 h. After completion of the reaction, the mixture was cooled to room temperature, acidified to neutral, extracted with dichloromethane (30 ml), washed with water, and the organic phase was dried over anhydrous MgSO4. Column chromatography was carried out to obtain the final target product Lc-4, yield 56.9%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
56.9% | With sodium methylate; In methanol; at 35℃; for 24h; | 7.38 g (11 mmol) of intermediate mc-6 and 2,6-dimethylpyranone 0.62 g (5 mmol) and 0.42 g (11 mmol) of fresh sodium methoxide were reacted in 30 ml of methanol at 35 C for 24 h. After completion of the reaction, the mixture was cooled to room temperature, acidified to neutral, extracted with dichloromethane (30 ml), washed with water, and the organic phase was dried over anhydrous MgSO4. Column chromatography was carried out to obtain the final target product Lc-6, yield 52.7%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With sodium methylate; In methanol; at 20℃; for 24h; | General procedure: To a magnetically stirred mixture of 1 mmol pyranilidenederivatives (1 or 3) in dry MeOH, the appropriate amount(1 or 2 mmol) of 4-bromobenzaldehyde and same amountof NaOMe were added. After 24 h in room temperature,the reaction mixture was filtrated and obtained precipitatewas purified with recrystallization in MeOH. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | With sodium methylate; In methanol; at 20℃; for 24h; | General procedure: To a magnetically stirred mixture of 1 mmol pyranilidenederivatives (1 or 3) in dry MeOH, the appropriate amount(1 or 2 mmol) of 4-bromobenzaldehyde and same amountof NaOMe were added. After 24 h in room temperature,the reaction mixture was filtrated and obtained precipitatewas purified with recrystallization in MeOH. |
Precautionary Statements-General | |
Code | Phrase |
P101 | If medical advice is needed,have product container or label at hand. |
P102 | Keep out of reach of children. |
P103 | Read label before use |
Prevention | |
Code | Phrase |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P210 | Keep away from heat/sparks/open flames/hot surfaces. - No smoking. |
P211 | Do not spray on an open flame or other ignition source. |
P220 | Keep/Store away from clothing/combustible materials. |
P221 | Take any precaution to avoid mixing with combustibles |
P222 | Do not allow contact with air. |
P223 | Keep away from any possible contact with water, because of violent reaction and possible flash fire. |
P230 | Keep wetted |
P231 | Handle under inert gas. |
P232 | Protect from moisture. |
P233 | Keep container tightly closed. |
P234 | Keep only in original container. |
P235 | Keep cool |
P240 | Ground/bond container and receiving equipment. |
P241 | Use explosion-proof electrical/ventilating/lighting/equipment. |
P242 | Use only non-sparking tools. |
P243 | Take precautionary measures against static discharge. |
P244 | Keep reduction valves free from grease and oil. |
P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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