* 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.
With ammonia In water at 120℃; for 0.333333 h; Microwave irradiation
2,6-Dimethyl-pyridin-4-ol (90) EPO <DP n="254"/>Five separate batches of dehydroacetic acid (1.5 g, 8.92 mmol) are each suspended in cone, ammonia (4 mL) and irradiated at 120°C for 20 minutes (150 W, Discover.(R). System microwave reactor by CEM Corporation, Matthews, North Carolina, USA) in the microwave. Once cooled, the solutions are combined and evaporated to dryness to afford the title compound.Yield: 5.91 g (108percent) (at) 73percent purity by LC/MS. The remaining mass balance is unreacted dehydroacetic acid.LC/MS tτ 0.67 min.MS(ES+) m/z 168 (M+CH3CN+H).
100%
With ammonia In water at 120℃; for 0.333333 h; Microwave irradiation
2,6-Dimethyl-pyridin-4-ol (90); EPO <DP n="254"/>Five separate batches of dehydroacetic acid (1.5 g, 8.92 mmol) are each suspended in cone, ammonia (4 mL) and irradiated at 120°C for 20 minutes (150 W, Discover.(R). System microwave reactor by CEM Corporation, Matthews, North Carolina, USA) in the microwave. Once cooled, the solutions are combined and evaporated to dryness to afford the title compound.Yield: 5.91 g (108percent) (at) 73percent purity by LC/MS. The remaining mass balance is unreacted dehydroacetic acid.LC/MS tτ 0.67 min.MS(ES+) m/z 168 (M+CH3CN+H).
100%
With ammonia In water at 120℃; for 0.333333 h; microwave irradiation
Synthesis of Compound Rl.; 2,6-Dimethyl-pyridin-4-ol (90); Five separate batches of dehydroacetic acid (1.5 g, 8.92 mmol) are each suspended in cone, ammonia (4 mL) and irradiated at 120°C for 20 minutes (150 W, Discover.(R). System microwave reactor by CEM Corporation, Matthews, North Carolina, USA) in the microwave. Once cooled, the solutions are combined and evaporated to dryness to afford the title compound.Yield: 5.91 g (108percent) (at) 73percent purity by LC/MS. The remaining mass balance is unreacted dehydroacetic acid.LC/MS tr 0.67 min.MS(ES+) m/z 168 (M+CH3CN+H).
Reference：
[1] Patent: WO2008/57497, 2008, A2, . Location in patent: Page/Page column 252-253
[2] Patent: WO2008/57469, 2008, A1, . Location in patent: Page/Page column 252-253
[3] Patent: WO2008/57468, 2008, A1, . Location in patent: Page/Page column 252-253
[4] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1988, vol. 42, # 6, p. 373 - 377
[5] Chemische Berichte, 1887, vol. 20, p. 159
[6] Chemische Berichte, 1885, vol. 18, p. 452[7] Monatshefte fuer Chemie, 1885, vol. 6, p. 104
[8] Journal of the Chemical Society, 1898, vol. 73, p. 238
[9] Patent: WO2007/89669, 2007, A2, . Location in patent: Page/Page column 164-165
2
[ 520-45-6 ]
[ 4344-87-0 ]
Reference：
[1] Chemische Berichte, 1894, vol. 27, p. 791[2] Journal fuer Praktische Chemie (Leipzig), 1895, vol. <2> 51, p. 61
3
[ 520-45-6 ]
[ 5093-70-9 ]
Reference：
[1] Acta Chemica Scandinavica, Series B: Organic Chemistry and Biochemistry, 1988, vol. 42, # 6, p. 373 - 377
Step A: Magnesium methoxide (6percent in MeOH, 530mL) was added to a suspension of dehydroacetic acid (31 g) in methanol (600 mL) at room temperature. The reaction mixture was refluxed and stirred for 5h. The solvent was removed and the residue dissolved in HCl 1M (1.5 L). The aqueous phase was extracted with EtOAc (2x 750 mL) and then the solvent was evaporated under reduced pressure to give a yellow oil, which was filtered on a silica cartridge using dichloromethane as eluent. After the solvent removal, methyl 3,5-dioxohexanoate was obtained as a light yellow oil (19.9 g).
With ammonia; In water; at 120℃; for 0.333333h;Microwave irradiation;
2,6-Dimethyl-pyridin-4-ol (90) EPO <DP n="254"/>Five separate batches of dehydroacetic acid (1.5 g, 8.92 mmol) are each suspended in cone, ammonia (4 mL) and irradiated at 120C for 20 minutes (150 W, Discover System microwave reactor by CEM Corporation, Matthews, North Carolina, USA) in the microwave. Once cooled, the solutions are combined and evaporated to dryness to afford the title compound.Yield: 5.91 g (108%) (at) 73% purity by LC/MS. The remaining mass balance is unreacted dehydroacetic acid.LC/MS ttau 0.67 min.MS(ES+) m/z 168 (M+CH3CN+H).
100%
With ammonia; In water; at 120℃; for 0.333333h;Microwave irradiation;
2,6-Dimethyl-pyridin-4-ol (90); EPO <DP n="254"/>Five separate batches of dehydroacetic acid (1.5 g, 8.92 mmol) are each suspended in cone, ammonia (4 mL) and irradiated at 120C for 20 minutes (150 W, Discover System microwave reactor by CEM Corporation, Matthews, North Carolina, USA) in the microwave. Once cooled, the solutions are combined and evaporated to dryness to afford the title compound.Yield: 5.91 g (108%) (at) 73% purity by LC/MS. The remaining mass balance is unreacted dehydroacetic acid.LC/MS ttau 0.67 min.MS(ES+) m/z 168 (M+CH3CN+H).
<= 100%
With ammonia; In water; at 120℃; for 0.333333h;microwave irradiation;
Synthesis of Compound Rl.; 2,6-Dimethyl-pyridin-4-ol (90); Five separate batches of dehydroacetic acid (1.5 g, 8.92 mmol) are each suspended in cone, ammonia (4 mL) and irradiated at 120C for 20 minutes (150 W, Discover System microwave reactor by CEM Corporation, Matthews, North Carolina, USA) in the microwave. Once cooled, the solutions are combined and evaporated to dryness to afford the title compound.Yield: 5.91 g (108%) (at) 73% purity by LC/MS. The remaining mass balance is unreacted dehydroacetic acid.LC/MS tr 0.67 min.MS(ES+) m/z 168 (M+CH3CN+H).
With ammonia; In water; at 120℃; for 0.333333h;Microwave irradiation 150 W;
Synthesis of Compound Rl2,6-Dimethyl-pyridin-4-ol (90)Five separate batches of dehydroacetic acid (1.5 g, 8.92 mmol) were each suspended in cone, ammonia (4 mL) and irradiated at 120C for 20 minutes (150 W, Discover <n="166"/>System microwave reactor by CEM Corporation, Matthews, North Carolina, USA) in the microwave. Once cooled, the solutions were combined and evaporated to dryness to afford the title compound.Yield: 5.91 g (108%) (at) 73% purity by LC/MS. The remaining mass balance is unreacted dehydroacetic acid. LC/MS _gamma 0.67 min. MS(ES+) m/z 168 (M+CH3CN+H).
With hydrogen;5%-palladium/activated carbon; In acetic acid; at 23℃; under 7500.75 Torr; for 24h;
A mixture of 1.0 G OF 3-ACETYL-6-METHYL-PYRAN-2, 4-DIONE, 100 mg of palladium-on-carbon (5 %) and 15 mi of acetic acid are hydrogenated at 23C under a hydrogen pressure of 10 bar for 24 hours. The catalyst is filtered off, washed well with tert-butyl methyl ether and the solution is concentrated to dryness by evanoration There are obtained 900 mg of colourless solid 3-acetyl-6-methyl-dihydro-pyran-2, 4- dione
A suspension of 3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione (500 g) in concentrated Eta2SO4 (800 mL) was stirred at 130 0C for 2 h. The mixture was poured into ice-water. The precipitate was collected by filtration, washed with hexane, and dried at 80 0C. A suspension of the above solid in25 28% aqueous NH3 was stirred at 1000C for 7 h. To the mixture was added water (1 L) and the mixture was neutralizing with concentrated HCl. The precipitate was collected by filtration, washed with water and acetone, and dried at 80 0C to give 6-methylpyridine-2,4-diol (135 g) as a pale brown solid. 1HNMR (300 MHz, DMSO-J6, delta): 2.08 (s, 3H), 5.34-5.37 (m, IH), 5.60-5.63 (m, IH), 10.30-10.61 (m, IH), 10.92-11.15 (m, IH); ESI MS m/z 126 (M++., 100%).
A mixture of 8,58 g of dehydroacetic acid with 7,63 g of N.N-Dimethylformamid-dimethyl- acetate in 100 ml of tert.-butylmethylether is stirred for 8 hours at room temperature. Then the product is filtered off, washed with minor amounts of tert.-butylmethylether and dried in vacuum at 400C. The yield is nearly quantitative. Fp: 159-161 0C.
1-(2,6-dimethyl-1,4-dihydropyridin-4-one)-1H-pyrrolo[2,3-b]pyridinium tetrafluoroborate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
A mixture of 1-amino-1H-pyrrolo[2,3-b]pyridinium 2,4,6-trimethylphenylsulfonate (16.6 g) and 3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione (8.8 g) in concentrated hydrochloric acid (40 mL) was stirred at reflux for 4 hours, then cooled and concentrated in vacuo. The residue was dissolved in ethanol (30 mL) and diluted with a solution of tetrafluoroboric acid in diethyl ether (54% v/v, 30 mL) and stirred for 1 hour at room temperature. Filtration gave the title compound (15.0 g) as a white solid, m.p. 247-248 C. 1H NMR [(CD3)2SO]: 9.24 (1H, d, J=7.5 Hz); 9.13 (1H, d, J=7.5 Hz); 8.08 (1H, d, J=4.2 Hz); 7.93 (1H, t, J=7.5 Hz); 7.22 (1H, d, J=4.2 Hz); 6.83 (2H, s); 1.96 (6H, s).
With boron trifluoride diethyl etherate; In acetic anhydride; at 23 - 85℃; for 2h;
34.2 g of dehydroacetic acid are stirred into 100 ml of acetic anhydride at 23C. 104 ml of boron trifluoride etherate are added dropwise to the beige suspension over a period of 30 minutes. The mixture is then heated at 85C for 11/2 hours, a yellow suspension being produced. After cooling to 25C, the suspension is filtered, followed by washing with 200 mi of diethyl ether and drying for 18 hours at 60C/104 Pa. There is obtained a light-yellow product of formula : 17.0 g of this light-yellow product are stirred in 150 mi of acetic anhydride, 15.5 g of diphenylformamidine are added and the mixture is heated at 65C for 2½ hours. The yellow suspension formed is filtered, followed by washing with 100 ml of diethyl ether and drying of the filter residue for 18 hours at 60C/10 4 Pa. There is obtained a yellow product of formula (cis isomerism of the enamine not confirmed): 2.55 g of this yellow product, together with 1.7 g of the intermediate product of Example 8 (benzoylacetone reacted with boron trifluoride etherate), are stirred in 20 ml of dichloromethane. 2 mi of acetic anhydride are then added and the mixture is then heated to reflux (40C). 2.2 ml of triethylamine are then added, whereupon the mixture immediately turns red. After refluxing for 2 hours, the mixture is allowed to cool to 20C. The precipitate that separates out is filtered off ; 50 ml of ether are added to the filtrate and the newly formed precipitate is filtered off. Both residues are combined, washed with 50 ml of diethyl ether and dried for 18 hours at 60oC/104 Pa. There is obtained a blue product of formula : UVNIS (DMF): No.max = 570 nm ; E=120500.
4-hydroxy-6-methyl-3-(4-nitrophenyl)acryloyl-2-pyrone[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
82%
In benzene;
Example 2 Synthesis of Compound 2 4-Nitrobenzaldehyde (4.5 g, 29.7 mmol) and then a number of drops of piperidine were added to a benzene (40 ml) solution of dehydroacetic acid (5.00 g, 29.7 mmol) at room temperature, after which refluxing was performed for 6 hours while eliminating water by azeotropy. The majority of the benzene was distilled of directly, and then the distillation taken to dryness under reduced pressure. Following which, when recrystallization was performed from ethanol, 4-hydroxy-6-methyl-3-(4-nitrophenyl)acryloyl-2-pyrone (7.3 g, 82%) was obtained as orange crystals. Tetrahydrofuran (250 ml), methanol (75 ml) and concentrated hydrochloric acid (25 ml) were added to the compound obtained (5.00 g, 16.6 mmol), then Pd-C (5%, containing 100% of water, 700 mg) added and the atmosphere replaced by hydrogen.
3-(2-dodecenoyl)-6-methyl-2H-pyran-2,4(3H)-dione[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
17%
In hexane; chloroform;
REFERENTIAL EXAMPLE 1 3-(2-Dodecenoyl)-6-methyl-2H-pyran-2,4(3H)-dione To a solution of 30.2 g (0.18 mole) of dehydroacetic acid and 30.0 g (0.19 mole) of decyl aldehyde in 300 ml of chloroform was added dropwise 4.8 g of piperidine at room temperature. The mixture was refluxed for 7 hours, while removing the water formed on the reaction with the aid of a Soxhlet extractor charged with anhydrous sodium sulfate. After the reaction, the reaction mixture was extracted with 600 ml of chloroform. The organic layer was separated, washed with 2N HCl and then with water, and dried over anhydrous sodium sulfate. The extract was concentrated under a reduced pressure and 60 ml of ether/hexane (1/2) was added to the residue. The mixture was allowed to stand overnight. The precipitated crystal was recovered by filtration and recrystallized from tetrahydrofuran to obtain 9.5 g (yield: 17%) of 3-(2-dodecenoyl)-6-methyl-2H-pyran-2,4(3H)-dione in the form of a white crystal, m.p. 112-113 C. 1 H-NMR(CDCl3) delta(ppm) 6.03(s,1H), 2.7-2.8(m, 2H), 2.39(s, 3H), 0.9-2.0(m, 19H).
2-anilino-4-methyl-6-acetonyl-pyrimidine[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
50%
With hydrogenchloride; potassium carbonate; In N-methyl-acetamide;
EXAMPLE 1 Preparation of 2-anilino-4-methyl-6-acetonyl-pyrimidine (VIII) Into a 500 ml reaction flask equipped with a stirrer, a thermometer and a condenser, 200 ml of dimethylformamide, 13.8 g (0.1 mol) of potassium carbonate, 39.6 g (0.2 mol) of phenylguanidine nitrate and 33.6 g (0.2 mol) of dehydroacetic acid were charged, and the reaction was conducted at 140 C. for 3 hours. After completion of the reaction, the reaction solution was cooled and put into ice water. Then, the reaction solution was extracted with toluene and washed with water. Then, 21 g (0.2 mol) of concentrated hydrochloric acid was dropwise added thereto. Precipitated crystals were collected by filtration, washed with toluene, then neutralized with an aqueous sodium carbonate solution and again extracted with toluene. This toluene layer was washed with water and concentrated to obtain 24.1 g of 2-anilino-4-methyl-6-acetonyl-pyrimidine having a melting point of from 77 to 80 C. The yield was 50%. From the following results of analyses, the product was confirmed to be the desired compound. IR(KBr): 740 cm-1, 1240 cm-1, 1440 cm-1, 1530 cm-1 1 H-NMR(CDCl3, delta): 1.9(s), 2.2(s), 2.3(s), 3.6(s), 5.1(s), 6.0(s), 6.4(s), 6.8-7.7(m), 13.8(br)
1,4-dihydro-2,6-dimethyl-4-oxo-1-(2,2,6,6-tetramethyl-4-piperidinyl)-3-pyridinecarboxylic acid[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
111 g (75.6%)
In hexane; water; toluene; benzene;
EXAMPLE 1 Preparation of 1,4-Dihydro-2,6-dimethyl-4-oxo-1-(2,2,6,6-tetramethyl-4-piperidinyl)3-pyridinecarboxylic acid A 1-liter, 3-neck, round-bottom flask was equipped with a mechanical stirrer, thermometer, and a Dean-Stark water trap topped with a water cooled condenser. The flask was charged with a mixture of 80.5 g (0.479 mol) dehydroacetic acid, 75.0 g (0.479 mol) 4-amino-2,2,6,6-tetramethylpiperidine, and 600 ml toluene. The stirred mixture in the flask was heated to the boiling point by means of an oil bath and the water formed during the reaction was collected in the trap. After 6 hours of reflux a total of 7.0 ml water had been collected and the flask and its contents cooled to room temperature. The mixture deposited crystals on standing which were collected by vacuum filtration. Reduction of volume of toluene in the filtrate caused a deposit of a second crop of crystals. The combined crystals were recrystallized from a 65/35 mixture of hexane/benzene to give 111 g (75.6%) of a white to colorless crystalline solid (M.P. 174 C.). The chemical structure and purity of these crystals were verified by mass spectroscopy, nuclear magnetic resonance spectroscopy; and by elemental analysis.
111 g (75.6%)
In hexane; water; toluene; benzene;
Example 1 Preparation of 1,4-Dihydro-2,6-dimethyl-4-oxo-1-(2,2,6,6-tetramethyl-4-piperidinyl)3-pyridinecarboxylic acid A 1-liter, 3-neck, round-bottom flask was equipped with a mechanical stirrer, thermometer, and a Dean-Stark water trap topped with a water cooled condenser. The flask was charged with a mixture of 80.5 g (0.479 mol) dehydroacetic acid, 75.0 g (0.479 mol) 4-amino-2,2,6,6-tetramethylpiperidine, and 600 ml toluene. The stirred mixture in the flask was heated to the boiling point by means of an oil bath and the water formed during the reaction was collected in the trap. After 6 hours of reflux a total of 7.0 ml water had been collected and the flask and its contents cooled to room temperature. The mixture deposited crystals on standing which were collected by vacuum filtration. Reduction of volume of toluene in the filtrate caused a deposit of a second crop of crystals. The combined crystals were recrystallized from a 65/35 mixture of hexane/benzene to give 111 g (75.6%) of a white to colorless crystalline solid (M.P. 174oC). The chemical structure and purity of these crystals were verified by mass spectroscopy, nuclear magnetic resonance spectroscopy, and by elemental analysis.
The extractor is filled with 125 g of type 3A molecular sieves and the flask with 80.5 g (0.479 mole) dehydroacetic acid, 500 ml methyl alcohol, and 20 g of concentrated (96%) sulfuric acid. The stirred mixture in the flask is heated to the boiling point by means of an oil bath. The resulting vapor is condensed and allowed to flow through the molecular sieves and returned to the flask. This process is continued for 24 hours. The cooled mixture is then diluted with 250 ml of methylene chloride and neutralized with aqueous caustic. Water is added to the mixture and the methylene chloride layer is separated from the resulting two-phase system. The water layer is extracted twice more with 250 ml amounts of methylene chloride. The combined methylene chloride extracts are washed twice with water, dried over magnesium sulfate, filtered free of solids, and the solvent is removed on a rotary evaporator. The residue is then subjected to vacuum distillation through a 10 inch Vigreaux column yielding 48 g of methyl 2,6-dimethyl-4-oxopyran-3-carboxylate boiling between 130-136 C. at 1.0 mm pressure. A 500 ml, 3-neck, round-bottom flask is equipped with a mechanical stirrer, thermometer and a Dean-Stark water trap topped with a water cooled condenser.
With sulfuric acid; In dichloromethane; water;
The extractor is filled with 125 g of type 3A molecular sieves and the flask with 80.5 g (0.479 mole) dehydroacetic acid, 500 ml methyl alcohol, and 20 g of concentrated (96%) sulfuric acid. The stirred mixture in the flask is heated to the boiling point by means of an oil bath. The resulting vapor is condensed and allowed to flow through the molecular sieves and returned to the flask. This process is continued for 24 hours. The cooled mixture is then diluted with 250 ml of methylene chloride and neutralized with aqueous caustic. Water is added to the mixture and the methylene chloride layer is separated from the resulting two-phase system. The water layer is extracted twice more with 250 ml amounts of methylene chloride. The combined methylene chloride extracts are washed twice with water, dried over magnesium sulfate, filtered free of solids, and the solvent is removed on a rotary evaporator. The residue is then subjected to vacuum distillation through a 10 inch Vigreaux column yielding 48 g of methyl 2,6-dimethyl-4-oxopyran-3-carboxylate boiling between 130-136oC at 1.0 mm pressure. A 500 ml, 3-neck, round-bottom flask is equipped with a mechanical stirrer, thermometer and a Dean-Stark water trap topped with a water cooled condenser.
Example 51 Preparation of 1-(3-hydroxyphenyl)-2,6-dimethyl-1H-pyridin-4-one hydrochloride 33b A mixture of dehydroacetic acid (25.4 g, 0.151 mol), 3-hydroxyaniline (15 g, 0.137 mol) and concentrated HCl (32 ml) was stirred in a 300 ml round bottom flask fitted with a rotary evaporator trap, a stir bar and a bubbler. The mixture was gradually warmed in an oil bath. At 130 C., a clear solution was obtained and gas evolution occurred. The bath temperature was slowly raised to 160 C. and kept at this temperature for 2 hours until gas evolution ceased. The mixture was cooled down to room temperature and a large amount of white crystals precipitated. Acetone was added to help with crystallization. Crystals were then collected by suction filtration and washed with acetone. The obtained white crystals (24.5 g, 71%) were used directly for the next step: m.p. 288 C. Example 52 Preparation of 1-[4-(2-ethylhexyloxy)phenyl]-2,6-dimethyl-1H-pyridin-4-one 34a
Example 50 Preparation of 1-(4-hydroxyphenyl)-2,6-dimethyl-1H-pyridin-4-one hydrochloride 33a A mixture of dehydroacetic acid (25.4 g, 0.151 mol), 4-hydroxyaniline (15 g, 0.137 mol) and conc. HCl (32 ml) was stirred in a 300 ml round bottom flask fitted with a rotary evaporator trap, a stir bar and a bubbler. The mixture was gradually warmed in an oil bath. At 130 C., a clear solution was obtained and gas evolution occurred. The bath temperature was slowly raised to 160 C. and kept at this temperature for 2 hours until gas evolution ceased. The mixture was cooled down to room temperature and a large amount of white crystals precipitated. Acetone was added to help with crystallization. Crystals were then collected by suction filtration and washed with acetone. The white crystals obtained (26.6 g, 77%) were used directly for the next step: m.p.>300 C.
Example 36; Step A methyl 3,5-dioxohexanoate; A solution of dehydroacetic acid (20.60 g; 168mmol) in methanol (40OmL) was treated with a solution of magnesium methoxide (6wt% in methanol; 350 mL; 184mmol) at ambient temperature. The reaction was refluxed for 5h. The solvent was removed and the residue added to aq. HCl (IL; IN). The aqueous was extracted (EtOAc, 2x500mL). The organic was dried over MgSO4, filtered and evaporated to give the title compound (17.0 g).
19.9 g
With methanol; for 5h;Reflux;
Step A: Magnesium methoxide (6% in MeOH, 530mL) was added to a suspension of dehydroacetic acid (31 g) in methanol (600 mL) at room temperature. The reaction mixture was refluxed and stirred for 5h. The solvent was removed and the residue dissolved in HCl 1M (1.5 L). The aqueous phase was extracted with EtOAc (2x 750 mL) and then the solvent was evaporated under reduced pressure to give a yellow oil, which was filtered on a silica cartridge using dichloromethane as eluent. After the solvent removal, methyl 3,5-dioxohexanoate was obtained as a light yellow oil (19.9 g).
With magnesium methanolate; In methanol; at 20℃; for 5h;Heating / reflux;
A solution of dehydroacetic acid (20.60 g; 168 mmol) in methanol (400 mL) was treated with a solution of magnesium methoxide (6 wt % in methanol; 350 mL; 184 mmol) at ambient temperature. The reaction was refluxed for 5 h. The solvent was removed and the residue added to aq. HCl (1 L; 1N). The aqueous was extracted (EtOAc, 2×500 mL). The organic was dried over MgSO4, filtered and evaporated to give the title compound (17.0 g).
In ethanol; for 0.00833333h;Microwave irradiation;
General Procedure: 2-Amino mono Schiff base ligand was synthesized by ethanolic mixture of DHA (0.1 mol) and aromatic diamines (0.1 mol) were placed in a flask and irradiated in a microwave oven for 30 s at 800 W. Completion of the reaction was monitored by TLC. The reaction mixture was allowed to attain RT. The solid mass obtained and recrystallized from methanol. 0.01 mol of 2-amiono mono Schiff base ligand and each pyrazolone ligands (I), (II) and (III) dissolved in DMF in a flask. The resulting mixture was irradiated in a microwave oven for 1 min at 800 W. The solid mass separated was poured into 1 l ice water in beaker. Brown colored precipitate of unsymmetrical tetradentate Schiff base ligands obtained. The resulting mixture was allowed to stand overnight. It was collected by filtration, washed with distilled water and petroleum ether, and dried.
With zinc/copper couple; hydrogen; In 1,4-dioxane; at 210℃; under 46544.6 - 63093.7 Torr; for 2.5h;Inert atmosphere; Sealed tube;
8.5 g of Copper zinc catalyst tablets were loaded into the steel tube hydrogenation reactor. A stream of 5% hydrogen/95% argon was passed over the catalyst at 0.5 lit/min as the catalyst was heated at 175 C. After reducing for about 18 hours overnight, the reactor was cooled and the catalyst was poured into a porcelain dish at room temperature under an argon atmosphere in a glove bag. 600 mg of DHAA was suspended in 1.2 ml of dioxane and heated with a heat gun. The hot dioxane was immediately added to the catalyst beads to wet the beads, the DHAA began to fall out of solution as the catalyst cooled. The catalyst beads were poured back into the hydrogenation reactor and it was sealed and removed from the glove bag. The reactor was then purged thrice with argon, twice with hydrogen and then filled to 1000 psi. The reactor was heated with the temperature rising to 210 C. Hydrogen was refilled as it was absorbed by the reaction and pressure varied between 900 and 1220 psi. After 2.5 hours an ice bath was placed to cool the liquid sampling tube, heating switched off and a liquid sample collected. GCMS of the sample indicated peaks for 4-heptanone, 4-heptanol, 2-heptanol and 1-butanol in a ratio of 14.2:71.4: 12.6: 1.5 respectively. Other products like 2,6-dimethyl-4-heptanol, n-heptane and 2,6- dimethylheptane were observed as lesser products.
With hydrogen; at 200 - 220℃; under 46544.6 - 56887.8 Torr; for 3.3h;Inert atmosphere; Sealed tube;
In the stainless steel inset was put 3.20 g of 2% Ru-alumina catalyst (Afa-Aesar) and 0.51 g of DHAA and the inset was placed inside of the reactor. The reactor was sealed and purged with argon and hydrogen three times each and then hydrogen filled to a pressure of 1100 psi. Heating was started and temperature of the catalyst bed was maintained at 200-220 C for 3.3 hours. The pressure drop related to hydrogen consumption was observed and in the end of hydrogenation it was 900 psi. The reactor was cooled down, purged with argon, the inset was removed and the catalyst was washed with 5 mL of methyl acetate. The resulting wash was filtered and analyzed by GC/MS. GCMS qualitative analysis of products formed is shown in Table 15 and also presents a theoretical estimation of the calorific value of a mixture. 100% DHAA reacted. 41% was a mixture of higher alcohols and ketones of which 27.7% was higher alcohols and 23.4% of that was heptanols.
With hydrogen; In 1,4-dioxane; at 180 - 207℃; under 37235.6 - 55853.5 Torr; for 2.5h;Inert atmosphere;
0.41 g of DHAA was dissolved in 1.5 mL of hot dioxane (99.8%) and the resulting homogenic solution was immediately pipetted evenly over 4.62 g of 2% Ru-alumina catalyst pellets (Alfa-Aesar). The resulting wetted catalyst was left to air for 30 minutes and then was poured into the reactor. The reactor was sealed and purged with argon and hydrogen three times each and then hydrogen was filled to a pressure of 1010 psi. Heating was started and temperature of the catalyst bed was maintained at about 200 C (180 - 207 C) for 2.5 hours. After 0.5 h the pressure in the reactor was dropped to 720 psi and was refilled with hydrogen to 1080 psi and it was 920 psi in the end of hydrogenation. The reactor was cooled down and a sample of liquid was collected from the reactor bottom and analyzed by GC/MS. The analysis indicated formation of compounds described in Table 1 below. Tables show an analysis of products using calorific values published from literature available on the National Institute of Standards and Technology website at nist.gov. For calorific values of molecules like 2-heptanol and 4-heptanol that were not readily available an isomer's heat of combustion like the 1-heptanol isomer's calorific value was used in calculations. The GCMS peaks were matched by agilent GCMS software to the NIST 2011 library of MS spectra. The quality of matches are listed on the last column of the table. The average energy of a fuel produced from the selected products of an experiment is on the last line of the tables. GCMS qualitative analysis of higher alcohols formed is shown in Table 14 and also presents a theoretical estimation of the calorific value of a mixture. 100% of DHAA was reacted. 33% of product observed was higher alcohols and some ketones. 18% higher alcohols were formed of which 16% was heptanols.
With hydrogen; at 161℃; under 15618.3 Torr; for 1.56667h;Inert atmosphere;
The hydrogenation reactor was filled with 297 g of copper chromite barium hydroxide catalyst and reduced with 5% hydrogen 95% nitrogen overnight at 195 C. The reduction was continued by replacing the hydrogen/argon mixture with hydrogen for another two hours to ensure proper reduction. The reactor was heated to about 350 C at the mid section of the reactor and hydrogen and DHAA flow started. Table 18 below describes some temperatures, pressure and flow rates for the reaction. Seven samples collected weighing 151 g. Total DHAA feed was 297 g. Reaction parameters and products seen in GCMS are shown in Tables 18 and 19 respectively. 100% of DHAA was hydrogenated. 53% of product was observed to contain higher alcohols, alkanes and ketones. 30% was hydrocarbons, 9% was higher alcohols of which 6% was heptanols. Samples were collected and analyzed by GCMS. Table 20 below describes compounds seen in the GCMS qualitative analysis and gives an estimation of the calorific value of a product sample of the reaction.
With hydrogen; In methanol; isopropyl alcohol; at 224 - 271℃; under 50164.7 - 60507.9 Torr; for 3h;Inert atmosphere; Sealed tube;
13 g of a copper chromite barium promoted catalyst containing about 62-64% Cr2Cu04, 22-24% CuO, 6% BaO, 0-4% Graphite, 1% Cr03, was weighed and added to the hydrogenation reactor described above. The reactor was sealed and a mixture of 5% hydrogen/95% nitrogen mixture was passed over the catalyst for about 18 hours at a temperature range of 155 to 180 C. The nitrogen/hydrogen gas mixture was replaced by a hydrogen gas stream and reduction was continued for another one hour at 180 C. The heating was shut off and system allowed to cool to room temperature. 0.5 g of DHAA was suspended in 1.5 ml of methanol and 1.5 ml of isopropanol and warmed gently with a heat gun until a clear solution was formed. The solution was quickly added to the catalyst bed and the reactor was sealed up. The reactor was pressurized with hydrogen at 1100 psi and was heated. Temperature rose to 271 C and the pressure rose to 1170 psi. Heating was decreased and temperature fell to 224 C. H2 pressure dropped to 970 psi over about one and half hour and was refilled to 1140 psi. After running for 3 hours the sampling tube was cooled, sample was taken and heating was shut off. GCMS of the sample indicated formation of 4-heptanol and n- heptane as major products in a ratio of 18.8: 16.7 area percents respectively. Other alcohols such as 2-butanol, 1-butanol, 2-pentanol, etc and alkanes such as 3 -methyl heptanes, 2,6-dimethyl heptanes, etc were observed in lesser amounts. All starting material was consumed. GCMS qualitative analysis of higher alcohols formed is shown in Table 17 and also presents a theoretical estimation of the calorific value of a mixture. 100% of DHAA was reacted. 63% of product mixture was observed to contain higher alcohols and alkanes. 32% were higher alcohols of which 17% was heptanols.
With zinc/copper couple; hydrogen; at 141℃; under 15566.6 Torr; for 2.4h;Inert atmosphere;
The reactor was filled with 544 g of copper zinc catalyst and reduced with 5% hydrogen 95% nitrogen overnight at 195 C. The reduction was continued by replacing the hydrogen/argon mixture with hydrogen for another two hours to ensure proper reduction. The reactor was heated to about 247 C at the mid section of the reactor and hydrogen and DHAA flow started. Table 21 below describes some temperatures, pressure and flow rates for the reaction. Total product collected was 182 g. Samples were collected and analyzed by GCMS. Reaction parameters and products seen in GCMS are shown in Tables 21 and 22 respectively. Table 23 below describes compounds seen in the GCMS qualitative analysis and gives an estimation of the calorific value of a product sample of the reaction. 100% of DHAA was hydrogenated. 73% of product was observed to contain higher alcohols, alkanes and ketone products, 14% was higher alcohols.
With zinc/copper couple; hydrogen; at 144℃; under 15514.9 Torr; for 3.33333h;Inert atmosphere;
The reactor was filled with 580 g of copper zinc catalyst and reduced with 5% hydrogen 95% nitrogen overnight at 195 C. The reduction was continued by replacing the hydrogen/argon mixture with hydrogen for another two hours to ensure proper reduction. The reactor was heated to about 300 C at the mid section of the reactor and hydrogen and DHAA flow started. Table 24 below describes some temperatures, pressure and flow rates for the reaction. 301 g of DHAA was reacted. Sixteen liquid samples were collected over the reaction amounting to 1 17 g of product collected. Samples were collected and analyzed by GCMS. Reaction parameters and products seen in GCMS are shown in Tables 24 and 25 respectively and graph 1 below. Table 26 below describes compounds seen in the GCMS qualitative analysis and gives an estimation of the calorific value of a product sample of the reaction. 100% of DHAA was converted. 75% of product included hydrocarbons and 2% of 4-nonanol. Graph 1 shows composition change of the mixture of the formed products with time and temperature.
The preparation of one representative ligand is presented here. 3-Acetyl-6-methyl-2H-pyran-2,4(3H)-dione (0.840 g, 0.005 mol) and benzoyl hydrazide (0.680 g, 0.005 mol) were dissolved separately in 50 mL of methanol each in a flask. Both solutions were mixed with stirring and the reaction mixture was refluxed on a water bath for 4 h. After cooling the reaction flask at room temperature for 3 h, the separated white solid was collected by filtration, washed with methanol and dried in a vacuum desiccator over silica gel. H2dha-bhz (I): Yield: 1.30 g (90%). Anal. Calc. for C15H14N2O4 (286.28): C, 62.93; H, 4.93; N, 9.79. Found: C, 62.7; H, 4.8; N, 9.7%.
The preparation of one representative ligand is presented here. 3-Acetyl-6-methyl-2H-pyran-2,4(3H)-dione (0.840 g, 0.005 mol) and benzoyl hydrazide (0.680 g, 0.005 mol) were dissolved separately in 50 mL of methanol each in a flask. Both solutions were mixed with stirring and the reaction mixture was refluxed on a water bath for 4 h. After cooling the reaction flask at room temperature for 3 h, the separated white solid was collected by filtration, washed with methanol and dried in a vacuum desiccator over silica gel. H2dha-inh (II): Yield: 1.22 g (84%). Anal. Calc. for C14H13N3O4 (287.27): C, 58.53; H, 4.56; N, 14.63. Found: C, 58.3; H, 4.5; N, 14.7%.
The preparation of one representative ligand is presented here. 3-Acetyl-6-methyl-2H-pyran-2,4(3H)-dione (0.840 g, 0.005 mol) and benzoyl hydrazide (0.680 g, 0.005 mol) were dissolved separately in 50 mL of methanol each in a flask. Both solutions were mixed with stirring and the reaction mixture was refluxed on a water bath for 4 h. After cooling the reaction flask at room temperature for 3 h, the separated white solid was collected by filtration, washed with methanol and dried in a vacuum desiccator over silica gel. H2dha-nah (III): Yield: 1.25 g (87%). Anal. Calc. for C14H13N3O4 (287.27): C, 58.53; H, 4.56; N, 14.63. Found: C, 58.7; H, 4.5; N, 14.6%.
The preparation of one representative ligand is presented here. 3-Acetyl-6-methyl-2H-pyran-2,4(3H)-dione (0.840 g, 0.005 mol) and benzoyl hydrazide (0.680 g, 0.005 mol) were dissolved separately in 50 mL of methanol each in a flask. Both solutions were mixed with stirring and the reaction mixture was refluxed on a water bath for 4 h. After cooling the reaction flask at room temperature for 3 h, the separated white solid was collected by filtration, washed with methanol and dried in a vacuum desiccator over silica gel. H2dha-fah (IV): Yield: 1.10 g (80%). Anal. Calc. for C13H12N2O5 (276.24): C, 56.52; H, 4.38; N, 10.14%. Found: C, 56.7; H, 4.3; N, 10.0%.
General procedure: Schiff bases with semicarbazone and thiosemicarbazone derivatives were prepared asfollows: a methanolic solution (10 mL) of dehydroacetic acid (Hdha) (0.168 g, 0.001 mol)was added to the methanolic solution (10 mL) of 4-phenyl-3-thiosemicarbazide (0.167 g,0.001 mol) (I) or thiosemicarbazide (0.091 g, 0.001 mol) (II) or 4-methyl-3-thiosemicarbazide(0.105 g, 0.001 mol) (III) or 4-phenylsemicarbazide (0.151 g, 0.001 mol) (IV). Theresulting solution was refluxed with stirring for 1-2 h at 50-60 C. The obtained filtratewas concentrated and left overnight at room temperature with solid precipitate of Schiffbases separating from their respective solutions. The obtained precipitate [44] was washedwith methanol, recrystallized from ethanol, and dried in vacuo.
General procedure: Schiff bases with semicarbazone and thiosemicarbazone derivatives were prepared asfollows: a methanolic solution (10 mL) of dehydroacetic acid (Hdha) (0.168 g, 0.001 mol)was added to the methanolic solution (10 mL) of 4-phenyl-3-thiosemicarbazide (0.167 g,0.001 mol) (I) or thiosemicarbazide (0.091 g, 0.001 mol) (II) or 4-methyl-3-thiosemicarbazide(0.105 g, 0.001 mol) (III) or 4-phenylsemicarbazide (0.151 g, 0.001 mol) (IV). Theresulting solution was refluxed with stirring for 1-2 h at 50-60 C. The obtained filtratewas concentrated and left overnight at room temperature with solid precipitate of Schiffbases separating from their respective solutions. The obtained precipitate [44] was washedwith methanol, recrystallized from ethanol, and dried in vacuo.
General procedure: Schiff bases with semicarbazone and thiosemicarbazone derivatives were prepared asfollows: a methanolic solution (10 mL) of dehydroacetic acid (Hdha) (0.168 g, 0.001 mol)was added to the methanolic solution (10 mL) of 4-phenyl-3-thiosemicarbazide (0.167 g,0.001 mol) (I) or thiosemicarbazide (0.091 g, 0.001 mol) (II) or 4-methyl-3-thiosemicarbazide(0.105 g, 0.001 mol) (III) or 4-phenylsemicarbazide (0.151 g, 0.001 mol) (IV). Theresulting solution was refluxed with stirring for 1-2 h at 50-60 C. The obtained filtratewas concentrated and left overnight at room temperature with solid precipitate of Schiffbases separating from their respective solutions. The obtained precipitate [44] was washedwith methanol, recrystallized from ethanol, and dried in vacuo.
General procedure: Schiff bases with semicarbazone and thiosemicarbazone derivatives were prepared asfollows: a methanolic solution (10 mL) of dehydroacetic acid (Hdha) (0.168 g, 0.001 mol)was added to the methanolic solution (10 mL) of 4-phenyl-3-thiosemicarbazide (0.167 g,0.001 mol) (I) or thiosemicarbazide (0.091 g, 0.001 mol) (II) or 4-methyl-3-thiosemicarbazide(0.105 g, 0.001 mol) (III) or 4-phenylsemicarbazide (0.151 g, 0.001 mol) (IV). Theresulting solution was refluxed with stirring for 1-2 h at 50-60 C. The obtained filtratewas concentrated and left overnight at room temperature with solid precipitate of Schiffbases separating from their respective solutions. The obtained precipitate [44] was washedwith methanol, recrystallized from ethanol, and dried in vacuo.
Methanolic solutions (10 mL) of ethylenediamine (10 mmol,0.667 mL), dehydroacetic acid (10 mmol, 1.68 g) and o-vanillin(10 mmol, 1.52 g) were mixed together and allowed to reflux for 5-6 h under constant stirring to result in the formation of a yellow precipitate. The solvent was reduced by slow evaporation followed by cooling. Finally the desired compound was washed with methanoland water several times, dried in vacuo over anhydrous CaCl2and recrystalized from ethanol.Analytical data: Chemical Formula: C18H20N2O5, MolecularWeight: 344, m/z: 344, 345 Decomposition Temperature:1115 C, Elemental Analysis Calc./Found (%): C, 62.78/62.55; H,5.85/5.78; N, 8.13/8.01; O, 23.23/23.10, IR data (cm-1): nuC=O;1696, nu=N; 1663, nuC=N; 1632, nu(OH); 3431; nuC-O; 1358, nuC=C; 1597,1580, 1469.
A solution of glucosamine hydrochloride (0.001 M, 0.215 g) in 20 mL methanol-water (50%)was treated with 10 mL aqueous solution of sodium bicarbonate (0.01 M, 0.84 g) followedby ltration. To the ltrate (0.001 M) dehydroacetic acid dissolved in 20 mL methanol wasadded. The resulting solution was reuxed with stirring for 4 h at 30-40 C. The desiredproduct was obtained by suction ltration of the respective precipitate formed on coolingovernight and was dried in vacuum. Analytical data: (dha-glsH2), empirical formula (formula mass): C14H19NO8 (330), Elementalanalysis: Found (calculated) (%): C 50.99 (51.06), H 5.60 (5.82), N 4.10 (4.25), white color,decomp. temp. (C): 155 and yield: 57%.
3-((2Ε,4Ε)-5-(4-chlorophenyl)-2,4-pentadienyl)-4-hydroxy-6-methyl-2H-pyran-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
75%
With benzoic acid; In acetonitrile; at 20℃;
<strong>[520-45-6]Dehydroacetic acid</strong> (50.4 mg, 0.3 mmol),4-chlorocinnamaldehyde (57.6 mg, 0.36 mmol),alpha,alpha-Diphenylhydrazine silyl ether (35.9 mg, 0.06 mmol),Benzoic acid (14.7 mg, 0.12 mmol) was added to the reaction vessel.Add solvent acetonitrile 2ml,Stir at room temperature,Until the TLC test is complete,After the reaction is complete,A large amount of yellow solids precipitated in the reaction vessel.The precipitated yellow solid was filtered, washed first with 1-2 mL of acetonitrile, then again with 2 mL of n-hexane, and dried to finally obtain the patchosterone derivative (yield 75%, purity ?98%)
With piperidine; In chloroform; at 60℃; for 12h;Inert atmosphere;
Dehydroacetic acid (500 mg, 2.97 mmol),3-formaldehyde benzothiophene (482.34 mg, 2.97 mmol) was dissolved in CHCl3 (4 ml).Piperidine (2d) was added dropwise,Nitrogen protection, reaction at 60 C for 12 h.The post-processing operation is the same as in Embodiment 1,A yellow solid was obtained, 507 mg (yield 54.59%).
(E)-3-(3-(cyclohex-3-en-1-yl)acryloyl)-4-hydroxy-6-methyl-2H-pyran-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55.43%
With piperidine; In chloroform; at 60℃; for 12h;Inert atmosphere;
<strong>[520-45-6]Dehydroacetic acid</strong> (500 mg, 2.97 mmol),3-cyclohexenecarbaldehyde (327.55 mg, 2.97 mmol) was dissolved in CHCl3 (4 mL).Piperidine (2d) was added dropwise,Nitrogen protection, reaction at 60 C for 12 h.The solvent CHCl3 was distilled off under reduced pressure, and a mixed solvent of DCM and PE was recrystallized.429 mg of a white solid were obtained (yield: 55.43%).
(E)-3-(3-(5-bromo-2-fluorophenyl)acryloyl)-4-hydroxy-6-methyl-2H-pyran-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
27.33%
With piperidine; In chloroform; at 60℃; for 12h;Inert atmosphere;
<strong>[520-45-6]Dehydroacetic acid</strong> (500 mg, 2.97 mmol),O-bromobenzaldehyde (603.66 mg, 2.97 mmol) was dissolved in CHCl3 (4 ml).Piperidine (2d) was added dropwise,Nitrogen protection, reaction at 60 C for 12 h.Post-processing is the same as in Embodiment 1,A yellow solid was obtained, 287 mg (yield: 27.33%).
With piperidine; In chloroform; at 60℃; for 12h;Inert atmosphere;
<strong>[520-45-6]Dehydroacetic acid</strong> (1 g, 5.95 mmol),P-nitrobenzaldehyde (898.74 mg, 5.95 mmol) was dissolved in CHCl3 (4 ml).Piperidine (2d) was added dropwise,Nitrogen protection, reaction at 60 C for 12 h.The solvent CHCl3 was distilled off under reduced pressure, and the ethanol was recrystallized.A yellow solid was obtained in 1.23 g (yield: 68.65%).
(E)-3-(3-(1H-indol-5-yl)acryloyl)-4-hydroxy-6-methyl-2H-pyran-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
57.85%
With piperidine; In chloroform; at 60℃; for 12h;Inert atmosphere;
The dehydroacetic acid (500mg, 2.97mmol)And 4-indolecarboxaldehyde (431.64 mg, 2.97 mmol) was dissolved in CHCl3 (4 ml).Piperidine (2d) was added dropwise,Nitrogen protection,The reaction was carried out at 60 C for 12 h.The solvent CHCl3 was distilled off under reduced pressure, and the ethanol was recrystallized.A yellow solid 508 mg (yield: 57.85%) was obtained.
(E)-3-(3-(1H-indol-4-yl)acryloyl)-4-hydroxy-6-methyl-2H-pyran-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
57.85%
With piperidine; In chloroform; at 60℃; for 12h;Inert atmosphere;
The dehydroacetic acid (500mg, 2.97mmol)And 4-indolecarboxaldehyde (431.64 mg, 2.97 mmol) was dissolved in CHCl3 (4 ml).Piperidine (2d) was added dropwise,Nitrogen protection,The reaction was carried out at 60 C for 12 h.Using the same post-treatment step in Example 1,A yellow solid 514 mg (yield: 57.85%) was obtained.
(E)-3-(3-(1H-indol-6-yl)acryloyl)-4-hydroxy-6-methyl-2H-pyran-2-one[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
57.85%
With piperidine; In chloroform; at 60℃; for 12h;Inert atmosphere;
<strong>[520-45-6]Dehydroacetic acid</strong> (500 mg, 2.97 mmol),Indol-6- carbaldehyde (431.64mg, 2.97mmol) was dissolved in CHCl3 (4ml),Piperidine (2d) was added dropwise,Nitrogen protection,The reaction was carried out at 60 C for 12 h.The post-processing operation is the same as in Embodiment 1,A yellow solid was obtained, 512 mg (yield: 58.31%).
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