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CAS No. : | 123-25-1 | MDL No. : | MFCD00009208 |
Formula : | C8H14O4 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | DKMROQRQHGEIOW-UHFFFAOYSA-N |
M.W : | 174.19 | Pubchem ID : | 31249 |
Synonyms : |
Diethyl Butanedioate
|
Num. heavy atoms : | 12 |
Num. arom. heavy atoms : | 0 |
Fraction Csp3 : | 0.75 |
Num. rotatable bonds : | 7 |
Num. H-bond acceptors : | 4.0 |
Num. H-bond donors : | 0.0 |
Molar Refractivity : | 43.14 |
TPSA : | 52.6 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) : | -6.51 cm/s |
Log Po/w (iLOGP) : | 2.09 |
Log Po/w (XLOGP3) : | 1.2 |
Log Po/w (WLOGP) : | 0.89 |
Log Po/w (MLOGP) : | 0.93 |
Log Po/w (SILICOS-IT) : | 1.17 |
Consensus Log Po/w : | 1.26 |
Lipinski : | 0.0 |
Ghose : | None |
Veber : | 0.0 |
Egan : | 0.0 |
Muegge : | 1.0 |
Bioavailability Score : | 0.55 |
Log S (ESOL) : | -1.21 |
Solubility : | 10.6 mg/ml ; 0.0611 mol/l |
Class : | Very soluble |
Log S (Ali) : | -1.9 |
Solubility : | 2.19 mg/ml ; 0.0126 mol/l |
Class : | Very soluble |
Log S (SILICOS-IT) : | -1.65 |
Solubility : | 3.92 mg/ml ; 0.0225 mol/l |
Class : | Soluble |
PAINS : | 0.0 alert |
Brenk : | 1.0 alert |
Leadlikeness : | 1.0 |
Synthetic accessibility : | 1.96 |
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P264-P273-P280-P305+P351+P338-P337+P313-P501 | UN#: | N/A |
Hazard Statements: | H319-H413 | 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 |
---|---|---|
59% | Stage #1: With sodium hydride; <i>tert</i>-butyl alcohol In 1,2-dimethoxyethane; mineral oil at 60℃; Inert atmosphere Stage #2: for 12 h; Inert atmosphere; Microwave irradiation; Reflux |
To a vigorously stirred suspension of NaH (60percent dispersion in mineral oil, 2.54 g, 63.5 mmol) in anhydrous DME (36 mL), t-BuOH (200μL, 2.2 mmol) was added and the mixture was heated to 60 °C under Ar. Diethyl succinate (1) (10 g, 57.4 mmol) was added dropwise over 30 min and the mixture was stirred overnight at 60 °C. The mixture was concentrated under reduced pressure and the resulting pink salt was suspended in distilled dibromoethane (28 mL, 325 mmol). The assembly was transferred to a microwave apparatus and the mixture heated at refluxed temperature by irradiation (80 W) for 12 h under Ar. After cooling, the suspension was filtered and the solid washed with CHCl3 (3 × 10 mL). The filtrate was concentrated under reduced pressure and the residue purified by column chromatography (cyclohexane–EtOAc, 8:2) to afford the title product. Yield: 4.73 g (59percent); white crystals; mp 111 °C. 1H NMR (400 MHz, CDCl3): δ = 1.30 (t, J = 7.2 Hz, 6 H), 2.09–2.15 (m, 2H), 2.46–2.56 (m, 2 H), 2.72 (d, J = 19.4 Hz, 2 H), 3.07 (dd, J = 19.4 Hz, 2.7 Hz, 2 H), 4.26 (q, J = 7.2 Hz, 4 H). 13C NMR (100 MHz, CDCl3): δ = 14.1, 24.5, 41.8, 57.3, 61.8, 168.6 ,203.7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With alumina methanesulfonic acid; at 80℃; for 0.133333h;Microwave irradiation; | General procedure: In a typical reaction, AMA 2:3 (332 g, 0.6 mol), the corresponding carboxylicacid (1 mol), and alcohol (1.5-2 mol) were mixed in the provided reaction glass tubeequipped with a screw cap and magnetic agitation until a wet mixture was achieved.The reaction mixture was irradiated with microwaves (Anton Parr Monowave 300reactor) at 80 C for 8 min or 120 C for 20 min. On cooling, the mixture was diluted with dichloromethane (41 mL), filtered under gravity, and washed with dichloromethane;then the filtrate was washed with Na2CO3 (ss) and water. The organic layerwas dried over Na2SO4, filtered, and concentrated under reduced pressure to give theester. |
60.8% | With carbon dioxide; at 180℃; under 20686.5 Torr; for 5h; | In FIG. 3D, free succinic acid was reacted at 180 C. under operational conditions in n-butanol, which generates dibutyl succinate at about 52.2% yield. |
With acidic cation exchange resin Amberlyst 70; at 50 - 160℃;Flow reactor; Green chemistry; | General procedure: Hexanedioic acid and methanol at a weight ratio of 1:5 were mixed at 50 C., and then introduced into the lower part of the vertical reactor at a liquid hourly space velocity (LHSV) of 6 hour-1. The reaction was performed at 130 to 175 C., as shown in Table 2. The reaction was performed at 115 C.. The esterized mixture was output from the upper part of the vertical reactor, and collected to be analyzed by gas photography. The acid value of the product was determined by titration, and the conversion rate and the selectivity were analyzed. The results were shown in Table 2. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; at 79.84℃; for 24h;Product distribution / selectivity; | EXAMPLE 9; Succinate recovery from fermentation products After demonstration of the process concept using pure succinate salts, a set of solids obtained from fermentation were subjected to theacidification/esterification process in EtOH. Characteristics of these solids are listed in Table 7.; Because of the high glucose content in sample labeled as W-l, a plasticlike sticky solid was obtained after drying. Melting of glucose made difficult water removal under experimental conditions. For this reason, dispersion and dissolution of particles within the reactive media was difficult. Other solids were dried without major difficulties and particle size reduction was conducted until fine-brownish dusts were obtained. Solids from batch 924-24m corresponded to crude SA obtained in the acid form because acidification was carried out in the aqueous broth before evaporation. In this case the amount of H2SO4 added was the required to catalyze esterification reaction (1 wt % of total solution).Acidification conditions for fermentation solids are listed in Table 8 and results are summarized in Table 9. Experiments ("runs") 21 and 22 were carried out in 2L batch reactors to evaluate the process in bench scale. In these runs reaction was performed under total reflux to avoid EtOH losses.; Even with excess of H2SO4, recovery of succinate and acetate species during ; acidification of solid W-1 was lower than that obtained with pure salts.After 2 h, around 40% recovery of succinate species was achieved compared with 80% in pure salts. However, after 24 h, comparable results with those obtained for pure solids are observed. This indicates that transport limitations are playing an important role in the process due to difficulties observed in dissolution of solids W-l. Figures 6A and 6B show the evolution of the recovery process in run 9 with Figure 6A showing succinate species and Figure 6B showing acetate species.Recovery on Runs 12 to 22 was in general lower compared with pure salts. In these experiments sulfuric acid loading was calculated only with respect to SA, therefore when stoichiometric ratio was used molar loading was about 86 % of the required to acidify all the acid species. This might explain the low recovery in experiments 12, 15 and 18. Remarkably, succinate esters were also produced during the process, confirming that H2SO4 acts as a catalyst before being consumed in salt acidification.Increasing H2SO4 loading enhances recovery as observed in experiments 13, 16 and 19 but temperature is still low to promote esterification. Operating at higher temperatures (333 and 383 K) similar recoveries to those obtained with pure salts were achieved as noticed in runs 20 and 21. In bench scale experiments with succinate salts and with crude SA (runs 21 y 22) high recovery and high conversion to MES and DES were obtained verifying feasibility of the process in a big scale. Evolution of succinate recovery in bench scale experiments is presented Figures 7A and 7B. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With sodium; In diethyl ether; at 40℃; for 5h; | To a suspension of sodium (333 mg, 14 mmol, 1.2 eq) in diethyl ether (7 mL) were added <strong>[123-25-1]succinic acid diethyl ester</strong> (2.1 g, 12 mmol, 1 eq) and formic acid ethyl ester (1.7 mL, 20 mmol, 1.7 eq). The mixture was stirred at 40 C. for 5 h. Water (10 mL) was added and the aqueous layer was washed with diethyl ether (2×10 mL). The aqueous layer was then acidified with a 6N solution of hydrochloric acid and extracted with diethyl ether (3×10 mL). The organic layers were dried over magnesium sulfate, filtered and evaporated in vacuo to afford the expected compound as orange oil (2.6 g, quant. yield). |
100% | With sodium; In diethyl ether; at 40℃; for 5h; | To a suspension of sodium (333 mg, 14 mmol, 1.2 eq) in diethyl ether (7 mL) were added <strong>[123-25-1]succinic acid diethyl ester</strong> (2.1 g, 12 mmol, 1 eq) and formic acid ethyl ester (1.7 mL, 20 mmol, 1.7 eq). The mixture was stirred at 40 C. for 5 h. Water (10 mL) was added and the aqueous layer was washed with diethyl ether (2×10 mL). The aqueous layer was then acidified with a 6N solution of hydrochloric acid and extracted with diethyl ether (3×10 mL). The organic layers were dried over magnesium sulfate, filtered and evaporated in vacuo to afford the expected compound as orange oil (2.6 g, quant. yield). |
95.1% | With sodium hydride; In toluene; at 20℃; for 16h; | Dry 10L four-neck flask, add 1800ml of toluene, 60% sodium hydride 200g, slightly hot stirring to disperse;Cool down to below 20C and add <strong>[123-25-1]diethyl succinate</strong> 871gAnd a mixture of ethyl formate 445g;After completion of the dropwise addition, the reaction mixture was stirred at room temperature for 16h until the material disappeared (GC monitoring).The reaction is completed, cooled to below 10 C, add ice water 2kg, stirring for 20min so that the basic full-solution, separation, toluene layer with water twice, each 300ml, combined water layer;The aqueous layer was adjusted to pH 3-4 with concentrated hydrochloric acid, stirred for 20 minutes until the pH was stable, the oil and water were separated, the aqueous layer was extracted three times with ethyl acetate, and the organic layers were combined and washed with saturated saline.The organic layer was dried under reduced pressure to recover ethyl acetate to give 960 g of a brownish-yellow transparent liquid with a yield of 95.1%. |
54% | Diethyl 2-formylsuccinate; To a mixture of sodium (1.66 g, 72.13 mmol) in diethyl ether (35 mL) was added <strong>[123-25-1]diethyl succinate</strong> (10 mL, 60.11 mmol) and ethyl formate (8.25 mL, 102.18 mmol) at room temperature, and the reaction mixture was refluxed for 5 hours. After the cooling to room temperature, water was added to the mixture until the sodium salt was dissolved completely and aqueous layer was separated. The aqueous layer was neutralized by 6M hydrochloric acid (10.8 mL) and extracted with diethyl ether. The extracts were washed with sat. NaHC03, dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by distillation (115- 120C, 10 mmHg) to give diethyl 2-formylsuccinate (6.55 g, 54%) as colorless oil. | |
53% | Intermediate 1; 5,5-dimethyl-7-[(1S' )-1-methylpropyI]-2-(methylsulfonyl)-5,7-dihydro-6H-pyrrolo[2,3- d] pyrimidin-6-one; Step 1 : Diethyl 2-formylsuccmate; Ethanol (27.0 g, 0.574 mol) was added dropwise to a suspension of sodium hydride (60 wt%, 23.0 g, 0.574 mol) in tetrahydrofuran (300 mL); the mixture was stirred at room temperature for 1 hour. Upon cooling to 10 C (cold water bath), solutions of <strong>[123-25-1]diethyl succinate</strong> (100 g, 0.574 mol) in tetrahydrofuran (100 mL) followed by ethyl formate (42.5 g, 0.574 mol) in tetrahydrofuran (100 mL) were added dropwise. After stirring for 16 h at room temperature, water (500 mL) was added and the resulting solution was washed with diethyl ether (2 x 250 mL). The water phase was acidified with 50% aq. H2SO4 and the resulting suspension was extracted with diethyl ether (2 x 250 mL). The combined organic layer was washed with water (3 x 200 mL), dried with sodium sulfate, filtrated through Celite, and concentrated under reduced pressure. The residue was distilled in vacuo (5 mm Hg) to afford 62.1 g (53% yield) of the desired diethyl 2-formylsuccinate, b.p. 90 C. <n="27"/>1H NMR (400 MHz, CDCl3) delta: 11.40 (d, J= 11.0 Hz, 0.5 H), 9.80 (s, 0.5 H), 7.00 (d, J= 11.0 Hz, 0.5 H), 4.30-4.00 (m, 4 H), 3.70-3.61 (m, 0.5 H), 3.00 (s, 1 H), 2.85-2.70 (m, 1 H), 1.28-1.10 (m, 6 H). | |
37% | With sodium; In diethyl ether; at 20℃; for 12h;Inert atmosphere; | 15.1. ethyl 2-formylbutanedioate To a suspension of 1.32 g (57.41 mmol) of sodium in 35 mL of anhydrous Et2O is added dropwise, at 0 C., under argon, a mixture of 10 g (57.41 mmol) of ethyl butanedioate and 4.62 mL (57.41 mmol) of ethyl formate. The medium is then stirred for 12 hours at room temperature, taken up in 100 mL of water and extracted with 100 mL of Et2O. The aqueous phase is acidified to pH 5 and then extracted with 100 mL of Et2O. The organic phase is then dried over Na2SO4, filtered and then concentrated under reduced pressure. The residue obtained is purified by chromatography on a column of silica gel, eluting with a 7/3 cyclohexane/EtOAc mixture. 4.3 g of ethyl 2-formylbutanediaote are obtained in the form of a colourless oil. Yield: 37% 1H NMR, 1H NMR, CDCl3, 400 MHz, delta (ppm): 10.0 (s, 1H); 7.1 (d, 1H); 4.4-4.2 (m, 5H); 2.9 (dd, 2H); 1.3 (m, 6H); |
With sodium; In ethanol; water; toluene; | (i) diethyl (RS)-formylsuccinate Ethanol (20 cm3) was added portionwise to a suspension of finely divided sodium (10.0 g) in dry toluene (100 cm3). On completion of the addition the mixture was heated for 3.5 hours at 80 C. To the resulting yellow suspension, cooled to 20 C., was added dropwise, over a period of 1 hour, a mixture of <strong>[123-25-1]diethyl succinate</strong> (70.0 g) and ethyl formate (35.0 g), whilst the temperature of the mixture was maintained in the range 20 to 30 C. The mixture was kept at the ambient temperature for 16 hours after which water (100 cm3) was added carefully. The aqueous layer was separated, neutralised with 50% aqueous sulphuric acid, and extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate, and concentrated by evaporation of the solvent under reduced pressure. The residual liquid (66 g) was subjected to fractional distillation under reduced pressure to obtain the desired diethyl (RS)-formylsuccinate (46.0 g), boiling range 82 to 86 C./0.53 mmHg. NMR spectroscopy indicated that the product exists as an approximately 1:1 mixture of keto and enol forms. 1 H NMR (CDCl3): 1.10-1.40 (m,3H) 2.90 (d, J=7Hz, 1H); 3.05 (s,1H); 3.75 (t, J=7 Hz, 0.5H); 4.00-4.40 (m,4H); 7.10 (d,J=11 Hz, 0.5H); 9.92 (s, 0.5 H); 11.5 (d, J=11 Hz, 0.5H). | |
With sodium; In ethanol; water; toluene; | EXAMPLE 2 The Example illustrates the preparation of diethyl (RS)-formylsuccinate. Ethanol (20 cm3) was added portionwise to a suspension of finely divided sodium (10.0 g) in dry toluene (100 cm3). On completion of the addition the mixture was heated for 3.5 hours at 80 C. To the resulting yellow suspension, cooled to 20 C., was added dropwise, over a period of 1 hour, a mixture of <strong>[123-25-1]diethyl succinate</strong> (70.0 g) and ethyl formate (35.0 g), whilst the temperature of the mixture was maintained in the range 20 to 30 C. The mixture was kept at the ambient temperature for 16 hours after which water (100 cm3) was added carefully. The aqueous layer was separated, neutralised with 50% aqueous sulphuric acid, and extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate, and concentrated by evaporation of the solvent under reduced pressure. The residual liquid (66 g) was subjected to fractional distillation under reduced pressure to obtain the desired diethyl (RS)-formylsuccinate (46.0 g), boiling range 82 to 86 C./0.53 mmHg. | |
With sodium; In ethanol; water; toluene; | (i) diethyl (RS)-formylsuccinate Ethanol (20 cm3) was added portionwise to a suspension of finely divided sodium (10.0 g) in dry toluene (100 cm3). On completion of the addition the mixture was heated for 3.5 hours at 80C. To the resulting yellow suspension, cooled to 20C, was added dropwise, over a period of 1 hour, a mixture of <strong>[123-25-1]diethyl succinate</strong> (70.0 g) and ethyl formate (35.0 g), whilst the temperature of the mixture was maintained in the range 20 to 30C. The mixture was kept at the ambient temperature for 16 hours after which water (100 cm3) was added carefully. The aqueous layer was separated, neutralised with 50% aqueous sulphuric acid, and extracted with diethyl ether. The ethereal extracts were washed with water, dried over anhydrous magnesium sulphate, and concentrated by evaporation of the solvent under reduced pressure. The residual liquid (66 g) was subjected to fractional distillation under reduced pressure to obtain the desired diethyl (RS)-formylsuccinate (46.0 g), boiling range 82 to 86C/0.53 mmHg. NMR spectroscopy indicated that the product exists as an approximately 1:1 mixture of keto and enol forms. 1H NMR (CDCl3): 1.10-1.40 (m,3H); 2.90 (d, J=7Hz, 1H); 3.05 (s,1H); 3.75 (t, J=7 Hz, 0.5H); 4.00 - 4.40 (m,4H); 7.10 (d,J=II Hz, 0.5H); 9.92 (s, 0.5 H); 11.5 (d, J= 11 Hz, 0.5H). Infra red (liquid film): 3300, 2980, 1735, 1665, 1175, 1030 cmmin1 | |
With sodium; In diethyl ether; at 0 - 20℃; for 17h;Inert atmosphere; | A mixture of <strong>[123-25-1]diethyl succinate</strong> (26.1 g, 25.0 mL, 0.150 mol) and ethyl formate (11.1 g, 12.1 mL, 0.150 mol) was added drop wise over 1.5 hours to a stirred suspension of sodium (3.40 g, 0. 50 mol) in diethyl ether (120 mL) at 0 C under nitrogen. On completion of addition, stirring was continued at room temperature for 7 hours. Water (120 mL) was cautiously added to the resulting suspension and stirring continued until ail the solids were dissolved. The layers were separated and the aqueous layer was washed with diethyl ether (100 mL). The aqueous layer was then acidified to pH 5 using 11 N HCI and extracted with diethyl ether (3x100 mL), the ethereal extracts of the acidified layer were combined, dried (Na2S04) then evaporated to dryness under reduced pressure to give the title compound (1705) (16.5 g) as a yellow mobile liquid. The crude product was not purified further and was used directly in the following step. | |
With sodium; In diethyl ether; at 0 - 20℃; for 17h;Inert atmosphere; | A mixture of <strong>[123-25-1]diethyl succinate</strong> (26.1 g, 25.0 mL, 0.150 mol) and ethyl formate (11.1 g, 12.1 mL, 0.150 mol) was added drop wise over 1.5 hours to a stirred suspension of sodium (3.40 g, 0.150 mol) in diethyl ether (120 mL) at 0 C under nitrogen. On completion of addition, stirring was continued at room temperature for 17 hours. Water (120 mL) was cautiously added to the resulting suspension and stirring continued until all the solids were dissolved. The layers were separated and the aqueous layer was washed with diethyl ether (100 mL). The aqueous layer was then acidified to pH 5 using 11 N HCI and extracted with diethyl ether (3x100 mL), the ethereal extracts of the acidified layer were combined, dried (Na2S04) then evaporated to dryness under reduced pressure to give the title compound (1 /05) (18.5 g) as a yellow mobile liquid. The crude product was not purified further and was used directly in the following step. | |
With sodium hydride; In tetrahydrofuran; ethanol; mineral oil; at 10 - 20℃; for 18h; | Step A: Diethyl 2-formylbutanedioate To a stirred suspension of sodium hydride (60% dispersion in mineral oil, 23.0 g, 0.574 mol) in THF (300 mL) was added EtOH (33.5 mL, 0.574 mol) dropwise. The resulting mixture was stirred at ambient temperature for 1 h then cooled to 10 "C and a solution of <strong>[123-25-1]diethyl succinate</strong> (96 mL, 0.574 mol) in THF (100 mL) was added dropwise, followed by a solution of ethyl formate (46.2 mL, 0.574 mol) in THF (100 mL) dropwise. The reaction mixture was stirred at ambient temperature for 18 h, then diluted with water (500 mL) and extracted with diethyl ether (2 x 250 mL), and these organic extracts were discarded. The aqueous layer was acidified to pH = 3-4 by addition of 50% aqueous sulfuric acid and extracted with diethyl ether (2 x 250 mL). The combined organic layers were washed with brine, dried over a2S04, filtered, and concentrated in vacuo. The residue was purified by vacuum distillation to afford the title compound (b.p. 90-92 C at 2 mm Hg). MS: m/z = 203.0 (M + 1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
64% | With sodium hydride; In 1,2-dimethoxyethane; tert-butyl alcohol; at 60℃; for 18h; | In the equipment with mechanical stirring, thermometer, dropping a funnel and a condenser tube in a 500 mL four-necked flask, 41.14 g (1.2 mol) of sodium hydride was suspended in 340 mL of ethylene glycol dimethyl ether, 1.5 g of t-butanol was added, the temperature was raised to 60 C, and 104.4 g (0.6 mol) of <strong>[123-25-1]diethyl succinate</strong> was started dropping, the rate of dropping is preferably controlled by the hydrogen produced. After completion of the dropwise addition (40 min-2 h), the reaction was continued with stirring to analyze the content of <strong>[123-25-1]diethyl succinate</strong> less than 1% to stop the reaction (18 h); Ethylene glycol dimethyl ether (boiling point 83 C) and ethanol (boiling point 78 C) were removed under reduced pressure, 10% dilute hydrochloric acid added to the kettle, adjust the PH value is weak acid, (1), the solid is succinic acid succinate (2) extracted with methylene chloride to the aqueous layer without diacetyl succinate, Steamed succinate succinate, purity 99%, yield 64%. |
60.4% | Sodium crumb (5.82 g, 253 mmol) was added in ethanol (60 mL) at room temperature, and then the reaction mixture was refluxed until the solid was dissolved. Diethyl succinate (1, 20 mL, 119 mmol) was added in the freshly prepared sodium ethanol/ethanol reagent. The mixture was refluxed for another 5 h. Ethanol was removed under reduced pressure. The residue was acidified with 2N sulfuric acid until the pH was about 2 with the precipitation of yellow solid. The reaction mixture was stirred at room temperature for 5 h. The precipitate was filtered, washed with water and dried at room temperature to afford crude product 2 which was recrystallized with ethyl acetate to obtain off-white crystalline solid (9.25 g, 60.4 %). mp 128--29C (Lit.26 128C) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | With C30H34Cl2N2P2Ru; potassium methanolate; hydrogen; In tetrahydrofuran; at 100℃; under 38002.6 - 76005.1 Torr; for 15h;Glovebox; Autoclave; | General procedure: In a glove box, add a ruthenium complex Ia (0.3 to 0.7 mg, 0.0002 to 0.001 mmol) to a 300 mL autoclave,Potassium methoxide (35-700 mg, 0.5-10 mmol), tetrahydrofuran (4-60 mL), and ester compounds (10-200 mmol).After sealing the autoclave, take it out of the glove box and fill it with 50 100atm of hydrogen.The reaction kettle was heated and stirred in an oil bath at 100 C for 10 to 336 hours.After the reaction kettle was cooled in an ice-water bath for 1.5 hours, the excess hydrogen was slowly released.The solvent was removed from the reaction solution under reduced pressure, and the residue was purified with a short silica gel column to obtain an alcohol compound. The results are shown in Table 5. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrazine hydrate; for 4h;Reflux; | Succinoyldihydrazine was prepared by reacting diethyl succinate (10.0 g, 49.50 mmol) with hydrazine hydrate (5.50 g, 110.00 mmol) under reflux for 4 hrs and recrystallized from methanol. | |
With hydrazine hydrate; In ethanol; | Ligand preparation involves two steps. In the frst step, it involved condensation of diethylsuccinate with hydrazine hydrate in 1:2.5 molar ratio in ethanol to give succinoyldihydrazide.In the second step, condensation of succinoyldihydrazide (2 g, 13.70 mmol) with2-hydroxy-1-benzaldehyde (3.68 g, 30.16 mmol) and 2-hydroxy-1-naphthaldehyde (5.19 g,30.16 mmol) gave the desired ligands H4slsch and H4npsch in moderate yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | To a vigorously stirred suspension of NaH (60% dispersion in mineral oil, 2.54 g, 63.5 mmol) in anhydrous DME (36 mL), t-BuOH (200muL, 2.2 mmol) was added and the mixture was heated to 60 C under Ar. Diethyl succinate (1) (10 g, 57.4 mmol) was added dropwise over 30 min and the mixture was stirred overnight at 60 C. The mixture was concentrated under reduced pressure and the resulting pink salt was suspended in distilled dibromoethane (28 mL, 325 mmol). The assembly was transferred to a microwave apparatus and the mixture heated at refluxed temperature by irradiation (80 W) for 12 h under Ar. After cooling, the suspension was filtered and the solid washed with CHCl3 (3 × 10 mL). The filtrate was concentrated under reduced pressure and the residue purified by column chromatography (cyclohexane-EtOAc, 8:2) to afford the title product. Yield: 4.73 g (59%); white crystals; mp 111 C. 1H NMR (400 MHz, CDCl3): delta = 1.30 (t, J = 7.2 Hz, 6 H), 2.09-2.15 (m, 2H), 2.46-2.56 (m, 2 H), 2.72 (d, J = 19.4 Hz, 2 H), 3.07 (dd, J = 19.4 Hz, 2.7 Hz, 2 H), 4.26 (q, J = 7.2 Hz, 4 H). 13C NMR (100 MHz, CDCl3): delta = 14.1, 24.5, 41.8, 57.3, 61.8, 168.6 ,203.7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | With Na on glass 100 mesh support In tetrahydrofuran at 45℃; for 1.5h; | |
70% | With Na-Glass In tetrahydrofuran at 45℃; for 2h; | |
With sodium In toluene |
(i) Na, toluene, (ii) /BRN= 1209232/; Multistep reaction; | ||
> 83 %Chromat. | With benzophenone; sodium In toluene at 50℃; Inert atmosphere; | 1 Example 1 1), under dry nitrogen protection,To the reactor equipped with a reaction substrate diethyl 1,4-succinate were successively introduced into dry toluene,Trace amount of benzophenone and put into sodium metal, the reaction mixture is fully blue,The anhydrous toluene and traces of benzophenone were added in an amount corresponding to 2 L of solvent per mole of the reaction substrate,The addition of sodium metal is 4 times the molar amount of the reaction substrate;2), and then warmed to 50 , the reactor was added dropwise sequentially,Or at the same time dropping the reaction substrate diethyl 1,4-succinate,And 4-fold molar amount of diethyl 1,4-succinate trimethylchlorosilane;3), dropping completed, the reaction incubated 3-4 hours incubation, until the dark blue reaction solution disappeared,After stirring for an additional 1 hour, the insoluble NaCl was filtered off.The insoluble NaCl was 4 times the molar amount of diethyl 1,4-butanedioate as the reaction substrate.4), the filtrate was concentrated, followed by distilling off by-products of trimethyl ethoxy silane and toluene solvent;Trimethylethoxysilane by-product of the chemical formula TMSOEt,2 times the molar amount of diethyl 1,4-succinate;5), then vacuum distillation,A fraction of 75-76 ° C / 10-11 mmHg was collected,The product 1,2-bistrimethylsilyloxycyclobutene was obtained,Wherein the product 1,2-bistrimethylsilyloxycyclobutene has a yield of more than 83% by GC analysis,The chemical purity of the product is about 98%. |
With sodium In toluene Reflux; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Under an argon atmosphere, trifluoroacetic acid ethyl ester (107 ml_, 899 mmol) is added dropwise during 30 min. to a 60 % suspension of NaH in mineral oil (22.6 g, 940 mmol). The resulting white suspension is heated to 60 0C and succinic acid ethyl ester (62.0 ml_, 370 mmol) is added dropwise during 5 h. The reaction mixture is heated for 18 h at 65 0C, cooled down to room temperature and carefully added to a mixture of ice (130 mg) and a 6 M aqueous H2SO4 solution (200 ml_). The dark brown solution is extracted twice with TBME and the combined organic phases are washed with brine, dried over Na2SO4 and concentrated at reduced pressure to afford a brown oil. The crude product is purified by bulb- to-bulb distillation (100-120 0C, 1 mbar) to afford the title compound as a pale yellow liquid (77.9 g, 288 mmol, 78 %). MS (ES+): 271 (M(C10H13F3O5^H)+. | |
With sulfuric acid; sodium; | STEP A: Ethyl 5,5,5-trifluoro-4-oxo-3-ethoxycarbonyl-pentanoate 200 g of <strong>[123-25-1]diethyl succinate</strong> and 82 g of ethyl trifluoroacetate were mixed together and 13.2 g of sodium and 200 ml of ether were added over 5 minutes. The reaction medium was heated for 18 hours at 80 C., and then poured into 200 ml of iced 10N sulfuric acid. After decanting, drying and concentrating, the expected product was obtained which was used as is for the following step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
59% | With potassium 2-methylbutan-2-olate In pentan-1-ol at 108 - 110℃; for 2h; | |
43% | Stage #1: benzonitrile With sodium tert-pentoxide In tert-Amyl alcohol at 30℃; for 0.0833333h; Stage #2: With 1-butyl-3-methylimidazolium Tetrafluoroborate In tert-Amyl alcohol for 0.166667h; Stage #3: succinic acid diethyl ester In tert-Amyl alcohol at 30℃; for 14h; | (1a) Preparation of 1,4-diketo-3,6-diphenylpyrrolo [3, 4-c]pyrroles General procedure: Benzonitrile (2 ml, 20 mmol) was added to sodium tamyloxide (from sodium, 0.40 g, 17.4 mmol) in dry t-amylalcohol (5ml) and stirred for 5 min at 30°C, and then ionic liquid (0.1 ml) was added to the reaction mixture and stirredfor 10 min. Diethyl succinate (2 ml, 10 mmol) was added slowly at 30°C. Reactions were monitored by TLC and the solution was neutralized with HCl. The precipitated pigment was diluted using 20 ml water and filtrated. Filter cake was rinsed by methanol to remove the remained ionic liquids and dried at 80°C in the vacuum. 1a: Yellowish-red powder; m.p. > 300°C; FT-IR (KBr)(max cm-1): 3439 (NH); 2947(CH); 1654(C=O); 1346,1225(C-N); max/nm (DMSO) 506, 473; 1H-NMR (500 MHz,CDCl3): H 7.33-7.70 (10H, m, 10 CH), 10.43(2H, s, NH). |
31% | With sodium tert-pentoxide In tert-Amyl alcohol Heating; |
With potassium <i>tert</i>-butylate In tert-Amyl alcohol at 130℃; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83% | Sodium (4.94 g, 204 mmol) is partitively dissolved in a solution of 2-methyl-2-butanol (500 ml) and FeCl3 (60 mg). When the sodium is completely dissolved, 2-furonitrile (18.9 ml, 204 mmol) is added thereto, the mixture is stirred under argon at 110 C. for 5 minutes, diethyl succinate (10.0 ml, 71.6 mmol) is added thereto in a dropwise fashion, and the obtained mixture is reacted for 4 hours. The reactants are cooled down to 0 C., and acetic acid (30 ml) dissolved in 50 ml of methanol is added thereto. The obtained mixture is reacted for 30 minutes under a reflux condition and cooled down to 0 C., and methanol (300 ml) is additionally added thereto. The obtained dark black/purple precipitate is filtered, washed with methanol and water, and dried under vacuum at 40 C. to obtain a product (15.96 g, 59.5 mmol, a yield of 83%). | |
21% | General procedure: To argon filled oven-dried three-neck round-bottom flaskequipped with a magnetic stir bar, a dropping funnel and a refluxcondenser, potassiumtert-butoxide (7.72 g, 68.9 mmol) and tertamyl alcohol (35 mL) were added. The mixture was heated to100-110C for 1.5 h. To this mixture 2-thiophenenitrile (5.0 g,45.8 mmol) was injected in one portion and the stirring continuedat 105C for 30 min. A mixture of diethyl succinate (4.00 g,22.9 mmol) intert-amyl alcohol (10 mL) was added drop wise overa period of 1 h with rapid stirring. The mixture was then stirred at100-110C for a further 4 h, and then cooled to 50C. Then themixture was diluted with of methanol (30 mL) and neutralizedwith acetic acid (5 ml). The reaction mixture was then heated toreflux for 45 min before cooling to room temperature. The suspension was filtered over a Buchner funnel and the solid was washedwith hot methanol and water several times and dried under vacuum at 80C for 16 h to give the product |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium tert-pentoxide In tert-Amyl alcohol Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Amberlyst 15; at 120℃; | DIETHYL SUCCINATE EXAMPLE The reactive distillation experiment for esterification of succinic acid used a prereactor at 120C to produce Feed 1 stream from the prereactor stream as shown in Figure 47. The prereactor feed constitutes a 10:1 molar ratio of ethanol to succinic acid. The stream Feed 1 represents an equilibrium mixture. In the reactive distillation column, the conversion of residual succinic acid (SA) from Feed 1 is about 45%. Monoethyl succinate (MES) is also about 50% converted in the RD column to produce additional diethyl succinate, the desired final product. The results of this Example shown in Table 9 illustrate the capability of reactive distillation to produce diethyl succinate from succinic acid. Table 9 Results of Succinic Acid Esterification via Reactive Distillation (All values are species flow rates in g/min) Species Prereactor Feed 1 Feed 2 Distillate Bottoms Succinic acid 4.1 0.2 0 0 0.119 Monoethyl succinate 1.03 0 0 0.514 Diethyl succinate 4.73 0 0 5.39 EtOH 15.9 12.66 15 19.42 8.05 Water 1.29 0 1.36 0 Diethyl ether 0.096 0 0.10 0 TOTAL 20.0 20.0 15.0 20.9 14.1 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
44% | Reference Example 311 A mixture of sodium ethoxide (391 g) and diisopropyl ether (2 L) was added a mixture of diethyl succinate (500 g) and ethyl trifluoroacetate (836 g) at60 C over 3 hours. The reaction mixture was stirred overnight at60 C. The reaction mixture was poured into ice water (2 L) andconc. hydrochloric acid was added to adjust to pH 2. The mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried(MgS04) and concentrated to give an oily substance (796.2 g). A mixture of the obtained oily substance (796.2 g) and40% aqueous sulfuric acid solution (3.3 L) was refluxed overnight. The reaction mixture was added to ice (2 kg), and extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried(MgS04) and concentrated to give an oily substance (401.6 g). To a mixture of the obtained oily substance (401.6 g) and ethanol (1.5 L) was added hydrazine monohydrate (200 ml) at0 C and the mixture was refluxed overnight. The reaction mixture was concentrated and water was added to the residue. The mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, dried(MgS04) and concentrated. The residue was subjected to silica gel column chromatography, and 4,5- <Desc/Clms Page number 272>dihydro-6- (trifluoromethyl)-3-pyridazinone (209.57 g, yield 44%) was obtained as yellow crystals from a fraction eluted with ethyl acetate-hexane (2: 3, volume ratio). melting point:94-95 C.lH-NMR (CDC13)$ : 2.57-2. 85 (4H, m), 9.15(1H, brs). |
Yield | Reaction Conditions | Operation in experiment |
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50% | With sodium; magnesium; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethanol; | Part A: Preparation of ethyl 5-(2',4'-dichlorophenyl)-5-cyano-4-ketopentanoate A clean, dry 500 ml 3-neck R.B. flask was equipped with a reflux condenser, mechanical stirrer, addition funnel, and nitrogen inlet. The flask was charged with 600 ml of ethanol (distilled from magnesium turnings and stored over type 3A molecular sieves) followed by 30.0 g (1.30 mol) of sodium, and the reaction mixture stirred and heated until all the sodium had dissolved. The temperature of the reaction mixture was then raised to the reflux point, and a mixture of 186.03 g (1.00 mol) of 2,4-dichlorobenzyl cyanide and 261.3 g (1.50 mol) of diethylsuccinate added at a rapid drop rate through the addition funnel. The reaction mixture was refluxed for 12 hours, then approximately 2/3 of the ethanol was distilled off, the reaction mixture refluxed for two additional hours, cooled to room temperature, and poured into 600 ml of ice water. The basic solution was extracted twice with 300 ml of ether, and then acidified with 6 N HCl. An oil formed, and the aqueous acid solution was extracted twice with 250 ml portions of ether. The ether extract was washed twice with water, dried (MgSO4), and the ether stripped to leave 156.61 g (50% yield) of product as a viscous red oil. |
50% | With sodium; magnesium; In (2S)-N-methyl-1-phenylpropan-2-amine hydrate; ethanol; | Part A Preparation of ethyl 5-(2',4'-dichlorophenyl)-5-cyano-4-ketopentanoate A clean, dry 500 ml 3-neck R.B. flask was equipped with a reflux condenser, mechanical stirrer, addition funnel, and nitrogen inlet. The flask was charged with 600 ml of ethanol (distilled from magnesium turnings and stored over type 3A molecular sieves) followed by 30.0 g (1.3 0 mol) of sodium, and the reaction mixture stirred and heated until all the sodium had dissolved. The temperature of the reaction mixture was then raised to the reflux point, and a mixture of 186.03 g (1.00 mol) of 2,4-dichlorobenzyl cyanide and 261.3 g (1.50 mol) of diethylsuccinate added at a rapid drop rate through the addition funnel. The reaction mixture was refluxed for 12 hours, then approximately 2/3 of the ethanol was distilled off, the reaction mixture refluxed for two additional hours, cooled to room temperature, and poured into 600 ml of ice water. The basic solution was extracted twice with 300 ml of ether, and then acidified with 6 N HCl. An oil formed, and the aqueous acid solution was extracted twice with 250 ml portions of ether. The ether extract was washed twice with water, dried (MgSO4), and the ether stripped to leave 156.61 g (50% yield) of product as a viscous red oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With hydrogenchloride; In water; toluene; | Ethyl 3-ethoxycarbonyl-4-(pyrazin-2-yl)-4-oxobutyrate can be prepared by adding, over a period of 5 minutes at a temperature of about 35 C, a solution of 2-ethoxycarbonylpyrazine (228 g) and ethyl succinate (261 g) in anhydrous toluene (700 cc) to a suspension of sodium tert.-butoxide (144 g) in anhydrous toluene (300 cc). Thereafter the reaction mixture is stirred for 12 hours at a temperature of about 20 C, and then 12N hydrochloric acid (130 cc) and distilled water (1300 cc) are added. The organic phase is decanted, washed with distilled water (500 cc) and then dried over magnesium sulphate. After filtration and concentration to dryness under reduced pressure, ethyl 3-ethoxycarbonyl-4-(pyrazin-2-yl)-4-oxobutyrate (364 g) is obtained in the form of a red oil. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In toluene; | Example 7 Condensation of Bicyclo[3.2.1]octan-3-one With Diethyl Succinate 7.1 In a modified procedure, a solution of bicyclo[3.2.1]octan-3-one (VIb-) (5 g 0.04 mole) and diethyl succinate (7 g, 0.04 mole) dissolved in toluene (10 cm3), was added dropwise with stirring to a suspension of potassium t-butoxide (5.38 g, 10% excess) in toluene (50 cm3). Work up as before gave the half ester (23; R=H) in 90% yeild. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Description 2; Diethyl 6-fluoro-1,4-dihydroxy-2,3-naphthalenedicarboxylate; <n="26"/>Diethyl succinate (16.26ml, 98.1 mmol) was added to dimethyl 4-fluoro-1 ,2- benzenedicarboxylate (10.4g, 49.1 mmol) and LHMDS (1M in THF, 196ml, 196mmol) in THF (150ml) at 1O0C (internal) over 30 minutes. Allowed to warm to room temperature slowly. After 20 hours, 2M HCI (~500ml) was added to acidify to pH 5. The mixture was extracted with EtOAc, then the organics washed with water, brine, dried over magnesium sulphate and concentrated in vacuo to give a brown oil. This was purified by chromatography on silica gel eluting with EtOAc/hexane (2:98) to yield the title compound as a yellow solid (4.58g, 14.2mmol).LC/MS: Rt=3.50. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | To a solution of 3-methyl-1 H-pyrazole-4-carbaldehyde (9 g, 82 mmol) and diethyl succinate (57 g, 327 mmol) in t-butanol (50 mL), a solution of t-BuOK (37.3 g, 245 mmol) in t-butanol(40 mL) was added and the mixture was heated to 80 3C for 4 hours. The mixture was concentrated; the obtained residue was dissolved in water (50 mL), acidified (pH~2) using 6 N HCI and extracted with ethyl acetate (2x50 mL). The combined organic layers were washed with aqueous NaHCO3 (2x50 mL). The combined aqueous layers were acidified (pH~2) and extracted with ethyl acetate (2x100 mL). The combined ethyl acetate layers were washed with saturated aqueous NaCI (25 mL), dried over anhydrous Na2SO4 and concentrated to afford 3-(ethoxycarbonyl)-4-(3-methyl-1 H-pyrazol-4-yl)but-3-enoic acid (20 g, 100%) as gum. 1H NMR (CDCI3) delta 7.85 (s, 1 H), 7.65 (s, 1 H), 4.3 (t, 2H), 3.65 (s, 2H), 4.4 (s, 3H), 1.3 (t, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: 3-ethyl-1H-pyrazole-4-carbaldehyde; succinic acid diethyl ester With potassium <i>tert</i>-butylate; <i>tert</i>-butyl alcohol at 80℃; for 3h; Stage #2: With hydrogenchloride In water | 2 To a solution of 3-ethyl-1 H-pyrazole-4-carbaldehyde (2.2 g, 18 mmol) and diethyl succinate (12.3 g, 71.0 mmol) in t-butanol (15 mL) was added a solution of t-BuOK (8.08 g, 53.2 mmol) in t-butanol (10 mL). The mixture was heated to 80 eC for 3 hours before the mixture was concentrated. The obtained residue was dissolved in water (30 mL), acidified (pH~2) using 6 N HCI and extracted with ethyl acetate (2x30 mL). The combined organic layers were washed with aqueous NaHCO3 (2x50 mL). The combined aqueous layers were acidified (pH~2) and extracted with ethyl acetate (2x75 mL). The combined ethyl acetate layers were washed with saturated aqueous NaCI (25 mL), dried over anhydrous Na2SO4 and concentrated to afford ethyl 2-[(3-ethyl-1 H-pyrazol-4-yl)methylene]-4-oxopentanoate (4 g, 100%) as gum, which was taken as such into next step. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | In a flame dried schlenk round bottom flask, elementary sodium (3.180 g, 138.26 mmol, 5 equiv)was added to 2-methylbutan-2-ol (75 mL), the mixture was stirred at 110 C until completedissolution. The temperature was then decreased to 90 C and 2-thiophenecarbonitrile (8 mL, 85.83 mmol,3 equiv) was added in one portion, affording a brown medium. A solution of diethylsuccinate (4.8 mL,28.66 mmol, 1 equiv) in 2-methylbutan-2-ol (18 mL) was added dropwise and the solution was stirred at110 C overnight. A solution of acetic acid (20 mL) in methanol (100 mL) was added to the medium, resultingin the precipitation of a deep purple solid, collected by centrifugation. Several washes with hot methanol werecarried out until getting a colorless filtrate. The crude product was dried to give a purple powder (7.916 g,92% yield) and used without further purification. | |
To argon filled oven-dried three-neck round-bottom flaskequipped with a magnetic stir bar, a dropping funnel and a refluxcondenser, potassiumtert-butoxide (7.72 g, 68.9 mmol) and tertamyl alcohol (35 mL) were added. The mixture was heated to100-110C for 1.5 h. To this mixture 2-thiophenenitrile (5.0 g,45.8 mmol) was injected in one portion and the stirring continuedat 105C for 30 min. A mixture of diethyl succinate (4.00 g,22.9 mmol) intert-amyl alcohol (10 mL) was added drop wise overa period of 1 h with rapid stirring. The mixture was then stirred at100-110C for a further 4 h, and then cooled to 50C. Then themixture was diluted with of methanol (30 mL) and neutralizedwith acetic acid (5 ml). The reaction mixture was then heated toreflux for 45 min before cooling to room temperature. The suspension was filtered over a Buchner funnel and the solid was washedwith hot methanol and water several times and dried under vacuum at 80C for 16 h to give the product, 3,6-di (thiophen-2-yl)-2,5-dihydropyrrolo [3,4-c] pyrrole-1,4-dione (S-DPP) (1). Yield:3.6 g (26%) as a red solid. This compound was used without furtherpurification.1H NMR (DMSO-d6, 400 MHz) dppm: 7.30 (dd, 2H,),7.95 (d, 2H), 8.22 (d, 2H), 11.21 (s, 2H);13C NMR (DMSO-d6,400 MHz)dppm: 108.53, 128.65, 130.76, 131.23, 132.58, 136.11,and 161.58. | ||
3.6 g | To argon filled oven-dried three-neck round-bottom flaskequipped with a magnetic stir bar, a dropping funnel and a refluxcondenser, potassium tert-butoxide (7.70 g, 68.8 mmol) and tertamyl alcohol (35 mL) were added. The mixture was heated to100-110 C for 1.5 h. To this mixture 2-thiophenenitrile (5.0 g,45.8 mmol) was injected in one portion and the stirring was continued at 105 C for 30 min. A mixture of diethyl succinate (4.0 g,22.9 mmol) in tert-amyl alcohol (10 mL) was added drop wise overa period of 1 h with rapid stirring. The mixture was then stirred at100-110 C for a further 4 h and then cooled to 50 C. Then themixture was diluted with methanol (30 mL) and neutralized withacetic acid (5 ml).The reaction mixture was then heated to refluxfor 45 min before cooling to room temperature. The suspensionwas filtered through a Buchner funnel, and the solid was washedseveral times with hot methanol and water followed by dryingunder vacuum at 80 C for 16 h to get the product, 6-di(thiophen-2-yl)-2, 5-dihydropyrrolo [3, 4-c] pyrrole-1, 4-dione(S-DPP). Yield: 3.6 g (26%) as a red solid. This compound was usedwithout further purification. 1H NMR (DMSO-d6, 200 MHz) d 7.30(2H, dd, J1 = 6.0, J2 = 3.0), 7.95 (2H, d, J = 6.0), 8.22 (2H, d, J = 3.0),11.21 (2H, s); 13C NMR (DMSO-d6, 200 MHz) 108.53, 128.65,130.76, 131.23, 132.58, 136.11, 161.58. |
To argon filled, oven-dried three-neck round-bottom flaskequipped with a magnetic stir bar, a dropping funnel and a refluxcondenser, potassium tert-butoxide (7.70 g, 68.8 mmol) and tertamylalcohol (35 mL) were added. The mixture was heated to110 C for 1.5 h. To this mixture 2-thiophenenitrile (5.0 g, 45.8mmol) was injected in one portion and the stirring continued at105 C for 30 min. A mixture of diethyl succinate (4.00 g, 22.9 mmol) in tert-amyl alcohol (10 mL) was added drop wise over aperiod of 1 h with rapid stirring. The mixture was then stirred at100-110 C for further 4 h, and then cooled to 50 C. Then the mixturewas diluted with 30 mL methanol and neutralized with aceticacid (5 mL). The reaction mixture was then heated at reflux for 45min before cooling to room temperature. The suspension was filteredover a Buchner funnel and the solid was washed with hotmethanol and water and dried under vacuum at 80 C for 16 h togive the product, 3,6-di (thiophen-2-yl)-2, 5-dihydropyrrolo [3,4-c] pyrrole-1,4-dione (S-DPP) as a red solid (Yield: 3.6 g (26%)). Thiscompound was used without further purification. 1H NMR (DMSOd6,200 MHz) deltappm: 7.30 (2H, dd, J1 = 6.0, J2 = 3.0), 7.95 (2H, d, J =6.0), 8.22 (2H, d, J = 3.0), 11.21 (2H, s); 13C NMR (DMSO-d6, 200MHz) 108.53, 128.65, 130.76, 131.23, 132.58, 136.11, 161.58. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; at 29.84℃; for 6h;Product distribution / selectivity; | EXAMPLE 9; Succinate recovery from fermentation products After demonstration of the process concept using pure succinate salts, a set of solids obtained from fermentation were subjected to theacidification/esterification process in EtOH. Characteristics of these solids are listed in Table 7.; Because of the high glucose content in sample labeled as W-l, a plasticlike sticky solid was obtained after drying. Melting of glucose made difficult water removal under experimental conditions. For this reason, dispersion and dissolution of particles within the reactive media was difficult. Other solids were dried without major difficulties and particle size reduction was conducted until fine-brownish dusts were obtained. Solids from batch 924-24m corresponded to crude SA obtained in the acid form because acidification was carried out in the aqueous broth before evaporation. In this case the amount of H2SO4 added was the required to catalyze esterification reaction (1 wt % of total solution).Acidification conditions for fermentation solids are listed in Table 8 and results are summarized in Table 9. Experiments ("runs") 21 and 22 were carried out in 2L batch reactors to evaluate the process in bench scale. In these runs reaction was performed under total reflux to avoid EtOH losses.; Even with excess of H2SO4, recovery of succinate and acetate species during ; acidification of solid W-1 was lower than that obtained with pure salts.After 2 h, around 40% recovery of succinate species was achieved compared with 80% in pure salts. However, after 24 h, comparable results with those obtained for pure solids are observed. This indicates that transport limitations are playing an important role in the process due to difficulties observed in dissolution of solids W-l. Figures 6A and 6B show the evolution of the recovery process in run 9 with Figure 6A showing succinate species and Figure 6B showing acetate species.Recovery on Runs 12 to 22 was in general lower compared with pure salts. In these experiments sulfuric acid loading was calculated only with respect to SA, therefore when stoichiometric ratio was used molar loading was about 86 % of the required to acidify all the acid species. This might explain the low recovery in experiments 12, 15 and 18. Remarkably, succinate esters were also produced during the process, confirming that H2SO4 acts as a catalyst before being consumed in salt acidification.Increasing H2SO4 loading enhances recovery as observed in experiments 13, 16 and 19 but temperature is still low to promote esterification. Operating at higher temperatures (333 and 383 K) similar recoveries to those obtained with pure salts were achieved as noticed in runs 20 and 21. In bench scale experiments with succinate salts and with crude SA (runs 21 y 22) high recovery and high conversion to MES and DES were obtained verifying feasibility of the process in a big scale. Evolution of succinate recovery in bench scale experiments is presented Figures 7A and 7B. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; at 30℃; for 2h;Product distribution / selectivity; | EXAMPLE 6; The same experimental procedure described in Example 4 was followed. Each tube was loaded with 4.13 g of sodium succinate hexahydrate, 23.74 g of anhydrous ethanol, and 2.1 g of sulfuric acid, which corresponds to a 40% molar excess of H2SO4 relative to that required for acidification. Results of reaction are presented in Table 3. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; at 30℃; for 24h;Product distribution / selectivity; | EXAMPLE 8; Experiments were conducted using the methods described in Example 4, except that only one tube per experiment was used to obtain the final recovery of the carboxylic acids. The conditions and quantities of reagents used are given in Table 5. Results of the experiments are provided in Tables 6.Because succinic acid and acetic acid are formed simultaneously by the microorganisms involved in a number of fermentations, mixtures of succinate salts and acetate salts were subjected to the experimental method described in Example 4 for the purpose of demonstrating the recovery of multiple acids simultaneously. Thus, a mixture of sodium acetate and disodium succinate hexahydrate (Run 5) was used as a model for the simultaneous recovery of succinic and acetic acid via the proposed process. Run 6 involved an azeotropic mixture of ethanol and water was used in place of anhydrous ethanol to recover succinic acid from aqueous solution. Runs 7 and 8 were conducted with sodium and calcium succinate salts at conditions that facilitate a high level of recovery of the succinic acid. Runs 1-4 were discarded due to procedural errors.; These experiments demonstrate the effectiveness of the novel methods described herein for recovering mixtures of organic acids simultaneously. These results also demonstrate that azeotropic mixtures of ethanol and water, which are much less expensive than anhydrous ethanol, are suitable as solvents for the recovery scheme. The results obtained expand the scope of conditions where the proposed recovery scheme is effective.After demonstration of the process concept using pure succinate salts, a set of solids obtained from fermentation were subjected to theacidification/esterification process in EtOH. Characteristics of these solids are listed in Table 7. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sulfuric acid; at 79.84℃; for 24h;Product distribution / selectivity; | EXAMPLE 9; Succinate recovery from fermentation products After demonstration of the process concept using pure succinate salts, a set of solids obtained from fermentation were subjected to theacidification/esterification process in EtOH. Characteristics of these solids are listed in Table 7.; Because of the high glucose content in sample labeled as W-l, a plasticlike sticky solid was obtained after drying. Melting of glucose made difficult water removal under experimental conditions. For this reason, dispersion and dissolution of particles within the reactive media was difficult. Other solids were dried without major difficulties and particle size reduction was conducted until fine-brownish dusts were obtained. Solids from batch 924-24m corresponded to crude SA obtained in the acid form because acidification was carried out in the aqueous broth before evaporation. In this case the amount of H2SO4 added was the required to catalyze esterification reaction (1 wt % of total solution).Acidification conditions for fermentation solids are listed in Table 8 and results are summarized in Table 9. Experiments ("runs") 21 and 22 were carried out in 2L batch reactors to evaluate the process in bench scale. In these runs reaction was performed under total reflux to avoid EtOH losses.; Even with excess of H2SO4, recovery of succinate and acetate species during ; acidification of solid W-1 was lower than that obtained with pure salts.After 2 h, around 40% recovery of succinate species was achieved compared with 80% in pure salts. However, after 24 h, comparable results with those obtained for pure solids are observed. This indicates that transport limitations are playing an important role in the process due to difficulties observed in dissolution of solids W-l. Figures 6A and 6B show the evolution of the recovery process in run 9 with Figure 6A showing succinate species and Figure 6B showing acetate species.Recovery on Runs 12 to 22 was in general lower compared with pure salts. In these experiments sulfuric acid loading was calculated only with respect to SA, therefore when stoichiometric ratio was used molar loading was about 86 % of the required to acidify all the acid species. This might explain the low recovery in experiments 12, 15 and 18. Remarkably, succinate esters were also produced during the process, confirming that H2SO4 acts as a catalyst before being consumed in salt acidification.Increasing H2SO4 loading enhances recovery as observed in experiments 13, 16 and 19 but temperature is still low to promote esterification. Operating at higher temperatures (333 and 383 K) similar recoveries to those obtained with pure salts were achieved as noticed in runs 20 and 21. In bench scale experiments with succinate salts and with crude SA (runs 21 y 22) high recovery and high conversion to MES and DES were obtained verifying feasibility of the process in a big scale. Evolution of succinate recovery in bench scale experiments is presented Figures 7A and 7B. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With iron(III) chloride; sodium; In tert-Amyl alcohol; at 120℃; for 2h; | Sodium metal (75 mg, 3.26 mmol) was dissolved in tert-amylalcohol (10 mL), and then trace amounts of FeCl3 were added. Themixture was refluxed under an argon atmosphere at 100 C untilthe solution became clear. 4-bromobenzonitrile (0.5 g, 2.75 mmol)and <strong>[123-25-1]diethyl succinate</strong> (0.24 g, 1.38 mmol) were added to this solution.The mixture was refluxed at 120 C for 2 h, and then stirred atroom temperature for 24 h. The resulting mixture poured into20 mL of distilled water. The resulting red-colored solids werefiltered. The solids werewashed with cold MeOH and warm MeOH,respectively, finally dried in the oven.Yield 75%, FT-IR (KBr pellet, cm1): 3141 (aromatic nCH stretching),1639 (nC]O), 1603 (aromatic nC]C), 1493, 1438, 1323, 1193, 1140,1072, 1009, 817, 752, 695 cm1. 1H NMR (400 MHz, DMSO-d6d 2.48 ppm): d 7.71e7.85 (8H, multiplet) ppm. |
73% | General procedure: Para-bromobenzonitrile (3.66 g, 20 mmol) was added to sodium t-amyl oxide (from sodium, 0.40 g, 17.4 mmol) in dry t-amyl alcohol (5 ml) and stirred for 5 min at 100C, and then ionic liquid (0.1 ml) was added to the reaction mixture and stirred for 10 min. Diethyl succinate (2 ml, 10 mmol) was added slowly at 30C. Reaction was monitored by TLC and the solution was neutralized with HCl. The precipitated pigment was diluted using 20 ml water and filtrated off. Filter cake was rinsed by methanol to remove the remained ionic liquids and dried at 80C in the vacuum.1c: Red powder; m.p: 297C; IR (KBr) (max cm-1): 3439(NH); 2948 (CH); 1657 (C=O); 1346, 1225(C-N); max/nm(DMSO) 520, 473; 1H-NMR (500 MHz, CDCl3): =7.56 (4H, d, JHH 8.0 Hz, 4CH), 8.70 (4H, d, JHH 8.0 Hz, 4CH), 10.20(2H, s, 2NH). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With Ce(4+)*2HO4P(2-)*4.9H2O; In toluene; for 8h;Heating; Green chemistry;Catalytic behavior; | The mono ester was prepared in first step by taking equimolar proportion (0.025 mol) of acid and alcohol (malonic acid and ethanol for DEM, succinic acid and ethanol for DES, phthalic anhydride and 1-butanol for DBP,phthalic anhydride and 2-ethyl 1-hexanol for DOP) were taken in a round bottomed flask and the reaction mixture stirred at ?80Cfor DEM and DES, ?110C for DBP and ?140C for DOP for about10-15 min in absence of any catalyst and solvent. The dicarboxylic acid and anhydride get completely converted to the monoester,so that the acid concentration at this stage is taken as the ini-tial concentration.The obtained product (monoester) was then subjected to esterification reaction by addition of a second mole(0.025 mol) of respective alcohol, catalyst (0.10-0.20 g) and 15 mL solvent (toluene (110C) for DEM, DES and DBP, and xylene (140C)for DOP). The reactions were carried out optimizing several param-eters such as reaction time, catalyst amount and mole ratio of reactants. The temperature parameter has not been varied as dis-cussed in synthesis of monoesters. In all cases the round bottomed flask was fitted with Dean and Stark apparatus, with a condenser to remove water formed during the reaction. After completion of reac-tion, catalyst was separated by decantation and reaction mixture was distilled to obtain the product. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium In tert-Amyl alcohol at 110℃; for 48h; Schlenk technique; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
53% | With sodium hydride; In toluene; at 55℃; for 1.0h;Inert atmosphere; | To a suspension of NaH (410 mg, 10.24 mmol) in toluene, the solution of compound5 (822 mg, 4.1 mmol) and diethyl succinate (2.14 g, 12.29 mmol) in toluene was addedsimultaneously at room temperature. Then, the reaction mixture was heated up to 55 oCand stirred for 1 hour under nitrogen protection. After 1 hour, concentrated HCl solution(5 mL) and water (7 mL) was added. The mixture was extracted with 1 M Na2CO3 (20mL × 3) and the aqueous layers were collected. The combined aqueous layers wereacidified with HCl and then extracted with Et2O. The organic layers were collected,dried over Na2SO4 and concentrated under reduced pressure to get the reaction crude.The residue was purified with silica gel to give 718 mg of compound 6 in 53% yield. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | With potassium <i>tert</i>-butylate In tetrahydrofuran at 55℃; for 1h; | 1 21.0 g (86.7 mmol) of 4,4'-dimethylbenzophenone and 17.3 g (99.4 mmol) of diethyl succinate were dissolved in 200 ml of tetrahydrofuran, and the temperature was raised to 55 ° C. A tetrahydrofuran solution (200 ml) of 9.7 g (86.7 mmol) of potassium t-butoxide was added dropwise to this solution, and the mixture was stirred for 1 hour. After the reaction, the reaction mixture was washed with concentrated hydrochloric acid and then with water, and the solvent was removed to give the compound represented by the following formula (14), compound as an orange oil (29.3 g, 86.3 mmol, yield: 100%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With potassium tert-butylate; for 12h;Reflux; | General procedure: Was prepared by the Stobbe-Condensation of 4-fluorobenzophenone 7a (10g, 0.05 mol) with diethylsuccinate (8.7g, 0.05 mol) in presence of potassiumt-butoxide (obtained from potassium (1.95g, 0.05 mol)in t-butyl alcohol 100 ml) at reflux temp for 12 hr. Thecooled reaction mixture was treated with 5N HCl (75ml), concentrated to 50 ml and diluted with water (100ml). The Itaconic acid half esters were extracted intoether (2 x 60 ml) and then into saturated sodiumbicarbonate solution (2x 60 ml). The bicarbonatesolution was acidified with conc. HCl to give a brownsemisolid in 69% yield (11.32g). The Itaconic acidhalf esters were saponified by refluxing in methanol(60 ml) and water (60 ml) mixture containing NaOH(6g). The reaction mixture was acidified with conc.HCl to give a white solid. It was recrystallised frommethanol to give white solid in 76% yield (7.86g). M.P.100-102 0 . IR (KBr): 1704 (-CH2-C=O), 1668 (alpha,beta-unsatured C=O), 3490-3255 (Carboxylic OH), 1583(Conjugated C=C), 1598 (aromatic C=C); 1 H NMR(CDCl3): 3.66 (s, 2H, CH2), 6.83-7.16 (m, 3H, C3?-H,C4?-H & C5?-H), 7.34-7.89 (m, 6H, C2?-H, C6?-H, C2-H, C3-H, C5-H and C6-H), 9.7-10.0 (bs, 2H, COOH). [Found: C, 67.97, H, 4.29 C17H13FO4 requires C, 68.00, H,4.33%]. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With [methyl-3-(butyl-4-sulfonate) imidazolium]CuPW12O40; oxygen; at 159.84℃; under 6000.6 Torr; for 5h; | General procedure: In a typical process, 0.25 g lignin, 0.9 mmol POM-IL catalyst and 20 mL 100% ethanol werecharged into a 100 mL stainless autoclave (Andorra MED1220, Premex Co. Ltd.). After airpurging with pure oxygen five times and pressurizing to 0.8 MPa, the reactor was heated to thedesignated temperature and maintained for the desired time. Once the latter elapsed, the autoclavewas cooled rapidly to room temperature in an ice water bath. The reaction mixture was removedand the reactor was washed with anhydrous ethanol (3 5.0 mL). The IL catalyst was precipitatedat room temperature and used for the next run after drying (extra fresh catalyst was added tooffset transfer losses). The liquid mixture was then diluted by ethanol to 50 mL for qualitative andquantitative analysis, while dimethyl phthalate was used as the internal standard. When aqueoussolutions of ethanol were used, the spent mixture was rotary evaporated under reduced pressurefor solvent recovery. The concentrated liquor was esterified with 10 mL anhydrous ethanol at 373K for 2 h and then diluted to 50 mL with ethanol. Volatile products were qualitatively andquantitatively analyzed via gas chromatography-mass spectrometry (GC-MS) and gaschromatography-flame ionization detection (GC-FID). Residual lignin can be obtained throughsimple precipitation processes. Organosolv lignin was recovered as follows: 60 mL deionized water was added into 20 mL of the above reaction mixture causing precipitation. The mixture wasthen separated using centrifugation and was dried until a constant weight was obtained. For therecovery of dealkaline lignin the mixture obtained after reaction was acidified to pH=2 with 1.0mol L-1 HCl solution and the same procedure described for organosolv lignin was conducted.In the atmosphere investigation, a mixture of nitrogen and oxygen with various molar ratioswas used, while depolymerization of lignin was conducted at 433 K for 5.0 h in the single stageexperiments. For a typical two-stage process, the lignin was first depolymerized employing theaforementioned conditions. When the mixture was cooled to room temperature, an extra 0.8 MPanitrogen or oxygen was purged into the reactor and the reaction was heated to 433 K for 1.0 or 2.0h. The product separation and analysis procedure remained unchanged to that describedpreviously. In comparative and control experiments, a series of model compounds (monolignolsand potential intermediate products) were tested under the same procedures as that for lignin (i.e.,0.25 g model compound, 0.9 mmol POM-IL catalyst and 20 mL 100% ethanol solvent). Triplicateexperiments were conducted and the data shown in this study is the average. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With [methyl-3-(butyl-4-sulfonate) imidazolium]CuPW12O40; oxygen; at 159.84℃; under 6000.6 Torr; for 5h; | General procedure: In a typical process, 0.25 g lignin, 0.9 mmol POM-IL catalyst and 20 mL 100% ethanol werecharged into a 100 mL stainless autoclave (Andorra MED1220, Premex Co. Ltd.). After airpurging with pure oxygen five times and pressurizing to 0.8 MPa, the reactor was heated to thedesignated temperature and maintained for the desired time. Once the latter elapsed, the autoclavewas cooled rapidly to room temperature in an ice water bath. The reaction mixture was removedand the reactor was washed with anhydrous ethanol (3 5.0 mL). The IL catalyst was precipitatedat room temperature and used for the next run after drying (extra fresh catalyst was added tooffset transfer losses). The liquid mixture was then diluted by ethanol to 50 mL for qualitative andquantitative analysis, while dimethyl phthalate was used as the internal standard. When aqueoussolutions of ethanol were used, the spent mixture was rotary evaporated under reduced pressurefor solvent recovery. The concentrated liquor was esterified with 10 mL anhydrous ethanol at 373K for 2 h and then diluted to 50 mL with ethanol. Volatile products were qualitatively andquantitatively analyzed via gas chromatography-mass spectrometry (GC-MS) and gaschromatography-flame ionization detection (GC-FID). Residual lignin can be obtained throughsimple precipitation processes. Organosolv lignin was recovered as follows: 60 mL deionized water was added into 20 mL of the above reaction mixture causing precipitation. The mixture wasthen separated using centrifugation and was dried until a constant weight was obtained. For therecovery of dealkaline lignin the mixture obtained after reaction was acidified to pH=2 with 1.0mol L-1 HCl solution and the same procedure described for organosolv lignin was conducted.In the atmosphere investigation, a mixture of nitrogen and oxygen with various molar ratioswas used, while depolymerization of lignin was conducted at 433 K for 5.0 h in the single stageexperiments. For a typical two-stage process, the lignin was first depolymerized employing theaforementioned conditions. When the mixture was cooled to room temperature, an extra 0.8 MPanitrogen or oxygen was purged into the reactor and the reaction was heated to 433 K for 1.0 or 2.0h. The product separation and analysis procedure remained unchanged to that describedpreviously. In comparative and control experiments, a series of model compounds (monolignolsand potential intermediate products) were tested under the same procedures as that for lignin (i.e.,0.25 g model compound, 0.9 mmol POM-IL catalyst and 20 mL 100% ethanol solvent). Triplicateexperiments were conducted and the data shown in this study is the average. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With [methyl-3-(butyl-4-sulfonate) imidazolium]CuPW12O40; oxygen; at 159.84℃; under 6000.6 Torr; for 5h; | General procedure: In a typical process, 0.25 g lignin, 0.9 mmol POM-IL catalyst and 20 mL 100% ethanol werecharged into a 100 mL stainless autoclave (Andorra MED1220, Premex Co. Ltd.). After airpurging with pure oxygen five times and pressurizing to 0.8 MPa, the reactor was heated to thedesignated temperature and maintained for the desired time. Once the latter elapsed, the autoclavewas cooled rapidly to room temperature in an ice water bath. The reaction mixture was removedand the reactor was washed with anhydrous ethanol (3 5.0 mL). The IL catalyst was precipitatedat room temperature and used for the next run after drying (extra fresh catalyst was added tooffset transfer losses). The liquid mixture was then diluted by ethanol to 50 mL for qualitative andquantitative analysis, while dimethyl phthalate was used as the internal standard. When aqueoussolutions of ethanol were used, the spent mixture was rotary evaporated under reduced pressurefor solvent recovery. The concentrated liquor was esterified with 10 mL anhydrous ethanol at 373K for 2 h and then diluted to 50 mL with ethanol. Volatile products were qualitatively andquantitatively analyzed via gas chromatography-mass spectrometry (GC-MS) and gaschromatography-flame ionization detection (GC-FID). Residual lignin can be obtained throughsimple precipitation processes. Organosolv lignin was recovered as follows: 60 mL deionized water was added into 20 mL of the above reaction mixture causing precipitation. The mixture wasthen separated using centrifugation and was dried until a constant weight was obtained. For therecovery of dealkaline lignin the mixture obtained after reaction was acidified to pH=2 with 1.0mol L-1 HCl solution and the same procedure described for organosolv lignin was conducted.In the atmosphere investigation, a mixture of nitrogen and oxygen with various molar ratioswas used, while depolymerization of lignin was conducted at 433 K for 5.0 h in the single stageexperiments. For a typical two-stage process, the lignin was first depolymerized employing theaforementioned conditions. When the mixture was cooled to room temperature, an extra 0.8 MPanitrogen or oxygen was purged into the reactor and the reaction was heated to 433 K for 1.0 or 2.0h. The product separation and analysis procedure remained unchanged to that describedpreviously. In comparative and control experiments, a series of model compounds (monolignolsand potential intermediate products) were tested under the same procedures as that for lignin (i.e.,0.25 g model compound, 0.9 mmol POM-IL catalyst and 20 mL 100% ethanol solvent). Triplicateexperiments were conducted and the data shown in this study is the average. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75.89% | A 1000ml four-necked bottle with a stirring device is installed in a water bath, and the water bath is filled with iced saline.101.2 g (98%, 1.65 mol) of glacial acetic acid and 250 g of n-butanol were added to the four-necked flask, and stirred, and 81.3 g (98.3%, 0.622 mol) of <strong>[39620-04-7]3-chloro-2-aminopyridine</strong> was added.Another 82.2 g (82.0%, 0.654 mol) of n-butyl nitrite n-butanol solution was added to the constant pressure funnel.When the temperature in the four-necked bottle drops to -2 to -5 C, the n-butyl nitrite in the constant-pressure funnel is added dropwise to the four-necked bottle.Control the temperature in the bottle between -5 and 10 C.Incubate at about 0 C, detect <strong>[39620-04-7]3-chloro-2-aminopyridine</strong> content <0.5%, the reaction is over,About 1.9g of urea was added to the starch-KI test paper to detect no change in color.Example 4A 1000ml four-necked bottle with a stirring device is installed in a water bath, and the water bath is filled with iced saline.To a four-necked flask was added 109.8 g of diethyl succinate (98.8%, 0.623 mol).Charge the diazo liquid of Example 3 into the constant pressure funnel several times, and connect the vent tube to the four-necked bottleThe snorkel bottle is inserted below the liquid level and connected to an ammonia gas tank with a pressure of 5-10kPa.When the four-necked bottle is started to stir and the temperature in the bottle drops below 0 C,Add dinitrogen solution into the bottle, and introduce ammonia gas into the bottle.Keep the temperature in the four-necked flask at -5 to 15 C and the pH value to be 4 to 6.5. After the dropwise addition, keep the temperature at 0 to 15 C.Sampling, after HPLC detection of diazonium salt disappeared, switch to water bath heating, continue to pass ammonia to pH 9 10.5 ,,After incubating at 30 to 95 C for 2 hours, the temperature was lowered to room temperature, and glacial acetic acid was added to neutralize to pH 6.5.Dissolve the contents of the four-necked bottle at an absolute pressure of 1 to 5 mmHg and a maximum temperature of 85 C until it is nearly evaporated to dryness.Naturally cooled to normal temperature under vacuum,Obtained gray-yellow loose solid particles, washed with water, dried, and washed with a small amount of ethanol.129.8 g of off-white solid powder was obtained, with a melting point of 132.3 to 133.0, a content of 98.05% by HPLC, and a yield of 75.89%. |
Tags: 123-25-1 synthesis path| 123-25-1 SDS| 123-25-1 COA| 123-25-1 purity| 123-25-1 application| 123-25-1 NMR| 123-25-1 COA| 123-25-1 structure
[ 56149-52-1 ]
4-(4-Hydroxybutoxy)-4-oxobutanoic acid
Similarity: 1.00
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