| 86% |
With thionyl chloride for 2h; Heating; |
|
| 85% |
With thionyl chloride In toluene for 7.5h; Heating / reflux; |
A
The preparation of diphenylketene. The preparation of diphenylketene was carried out according to the published procedure starting from diphenylacetic acid. [Taylor, E. C. , et al. , Org Synth CV 6,549.] A. Diphenylacetyl chloride.; A 500 mL, three-necked flask equipped with a dropping funnel and a reflux condenser carrying a calcium chloride drying tube was charged with diphenylacetic acid (50.0 g, 0.236 mol) and anhydrous toluene (150 mL). The mixture was heated under reflux, and thionyl chloride (132 g, 80.1 mL, 1.11 mol) was added dropwise over 30 minutes. Refluxing was continued for 7 additional hours and then the toluene and excess thionyl chloride were removed by distillation under reduced pressure. The residue was dissolved in 150 mL of refluxing, anhydrous hexane. The hot solution was treated with charcoal and filtered, and the filtrate was cooled to 0°C in a sealed flask. The product, which crystallizes as colorless plates was filtered, washed with a little cold hexane, dried at 25°C under vacuum giving diphenylacetyl chloride (46 g, 85%), m. p. 51-52°C. |
| 68% |
With Amberlite IRA 93 (PCl5 form) In dichloromethane for 6h; Heating; |
|
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With thionyl chloride |
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With phosphorus(V) chloride |
|
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With phosphorus(V) chloride; trichlorophosphate |
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With thionyl chloride |
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With oxalyl dichloride In benzene for 3h; Ambient temperature; |
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With thionyl chloride In dichloromethane for 12h; Heating; Yield given; |
|
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With oxalyl dichloride In 1,4-dioxane for 3h; Heating; |
|
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With thionyl chloride for 15h; |
|
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With thionyl chloride at 90 - 100℃; for 3h; |
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With thionyl chloride for 1h; Heating; |
|
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With oxalyl dichloride; N,N-dimethyl-formamide In benzene for 2h; Ambient temperature; |
|
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With thionyl chloride In toluene for 4h; Heating; |
|
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With thionyl chloride for 2h; Heating; |
|
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With thionyl chloride for 2h; Heating; |
|
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With oxalyl dichloride In dichloromethane at 0 - 20℃; |
|
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With oxalyl dichloride; N,N-dimethyl-formamide In benzene for 18h; |
|
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With oxalyl dichloride |
|
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With thionyl chloride In benzene Heating; |
|
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With thionyl chloride for 0.75h; Heating; |
|
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With thionyl chloride for 0.25h; Heating; |
|
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With thionyl chloride In benzene for 4h; Heating; |
|
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With thionyl chloride In dichloromethane for 1.5h; Heating; |
|
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane for 12h; |
|
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With thionyl chloride In dichloromethane for 1.5h; Heating; |
|
| 100 % Spectr. |
With trichloroacetonitrile; triphenylphosphine In chloroform-d1 at 20℃; for 0.25h; |
|
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With thionyl chloride for 2h; Heating; |
|
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With thionyl chloride; N,N-dimethyl-formamide |
|
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h; |
|
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With thionyl chloride for 2h; Reflux; |
|
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; |
|
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With thionyl chloride In chloroform |
|
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With thionyl chloride at 20 - 50℃; for 1.5h; |
|
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With trichloroacetonitrile; triphenylphosphine In acetonitrile at 20℃; Inert atmosphere; |
|
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With thionyl chloride at 0℃; Reflux; |
|
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With thionyl chloride for 3h; Reflux; |
General procedure: Compound 10 was prepared by a procedure similar to that of Lu and co-workers, and Nagao and co-workers. A solution of octanoic acid (4.43g, 30.74mmol) and thionyl chloride (20mL) was heated under reflux for 3h. The excess thionyl chloride was removed in vacuo and the crude octanoyl chloride taken through to the next step without further purification. A solution of 2 (12.0g, 21.55mmol), triethylamine (4.6mL, 33.3mmol), dimethylaminopyridine (0.26g, 2.16mmol) and crude octanoyl chloride in dimethylformamide (150mL) was then stirred at room temperature for 3h. The mixture was then diluted with ethyl acetate (200mL) and washed with water (200mL). The separated aqueous phase was further extracted with ethyl acetate (2×100mL) and the combined organic phases washed with brine (4×100mL), dried over anhydrous magnesium sulfate, filtered and the solvent removed in vacuo. Purification by flash chromatography (hexane/ethyl acetate 2:1) afforded 10 as an off-white solid (9.92g, 14.66mmol, 68%). |
|
With thionyl chloride at 80℃; for 6h; |
|
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With oxalyl dichloride; N,N-dimethyl-formamide In chloroform at 20℃; for 1h; Inert atmosphere; |
|
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With thionyl chloride; N,N-dimethyl-formamide In toluene at 0℃; for 3h; Reflux; |
|
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With thionyl chloride Reflux; |
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With thionyl chloride Reflux; |
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With thionyl chloride Reflux; |
5.1.1. N-(3-Bromopropyl)-3,5-dichlorobenzamide (10a)
Compound 9a (191 mg, 1 mmol) was refluxed in excess of thionylchloride (3 mL) overnight. Excess of thionyl chloride was evaporatedand the residue was dissolved in CH2Cl2, 3-bromopropylamine hydrobromide (328 mg, 1.5 mmol was addedfollowed by triethylamine (TEA; 0.42 mL, 3 mmol). The reactionmixture was stirred at room temperature. After the reaction wascompleted, the reaction mixture was diluted with CH2Cl2 andsequentially washed with water, 1 N HCl and saturated NaHCO3.The organic layer was dried over MgSO4, filtered and concentrated.The obtained product was purified by column chromatographywith n-hexane/ethyl acetate (EtOAc) = 4:1 to obtain 10a, (236 mg,76%) as white solid. |
|
With I,I-bischloroiodobenzene; triphenylphosphine In dichloromethane for 0.166667h; Reflux; Inert atmosphere; |
|
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With thionyl chloride at 50 - 60℃; |
|
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With phosphorus trichloride at 50 - 60℃; |
In a 250 ml reaction flask, I (20.0 g) was added, stirred, phosphorus trichloride (100 ml) was added, heated to 50-60 ° C, the gas was absrobed from the lye, and reacted for 3-4 h. After completion of the reaction, the organic layer was separated to obtain brown liquid 2,2-diphenylacetyl chloride (formula II). |
|
Multi-step reaction with 2 steps
1: magnesium(II) sulfate; sulfuric acid / dichloromethane / 20 °C / Inert atmosphere
2: thionyl chloride; lithium hydroxide monohydrate / 20 °C / Sealed tube |
|
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With thionyl chloride In tetrahydrofuran; toluene; benzene Reflux; |
4.1.27. N-(2-Chloroethyl)-2,2-diphenylacetamide (18a)
Compound 17a (530 mg, 2.49 mmol) was refluxed in excess of thionyl chloride (10 mL) in presence of benzene for overnight. Excess of thionyl chloride and benzene was evaporated and the residue was dissolved in CH2Cl2, 2-chloroethylamine hydrochloride(432 mg, 3.73 mmol) was added followed by triethylamine(TEA; 1 mL, 7.47 mmol). The reaction mixture was stirred at room temperature. After the reaction was completed, the reaction mixture was diluted with CH2Cl2 and sequentially washed with water,1 N HCl and saturated NaHCO3. The organic layer was dried overMgSO4, filtered and concentrated. The obtained product was purified by column chromatography with n-hexane: Ethyl acetate(EtOAc) = 4:1 to obtain 18a (386 mg, 60%) as light yellow liquid.Rf = 0.82 (n-hexane: EtOAc = 1:1). 1H NMR (300 MHz, CDCl3): d7.43-7.33 (m, 11H), 3.73-3.65 (m, 4H). |
|
In dichloromethane at 20 - 80℃; for 1h; |
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With thionyl chloride In benzine for 24h; Inert atmosphere; Reflux; |
5.8. General procedure for the synthesis of diphenylacetic acid chloride (18)
A solution of diphenylacetic acid 17 (5 g, 23.56 mmol) in benzene (10 mL) was treated by the dropwise addition of SOCl2 (42 g, 0.35 mol, 26 mL) under nitrogen atmosphere. Then the reaction mixture was heated at reflux with stirring for 24 h, cooled to room temperature and stirred for another 24 h. Next, the excess of SOCl2 and benzene were removed under vacuum to obtained desired acid chloride 18 as a colorless oil, which solidified on standing. Diphenylacetic acid chloride (18) was further used without any purification. |
|
Stage #1: 2,2-diphenylacetic acid With oxalyl dichloride In dichloromethane for 0.333333h; Inert atmosphere;
Stage #2: With N,N-dimethyl-formamide In dichloromethane for 2h; Inert atmosphere; |
|
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With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 55℃; for 5h; |
|
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With thionyl chloride In dichloromethane for 6h; Reflux; |
|
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With tungsten hexachloride In dichloromethane-d2 for 18h; Inert atmosphere; |
|
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With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 0.5h; Inert atmosphere; |
|
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With thionyl chloride at 90℃; |
|
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With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 2h; |
|
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With chlorinating agent In dichloromethane at 0℃; |
|
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With thionyl chloride at 25℃; for 0.5h; Inert atmosphere; |
|
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With thionyl chloride In toluene at 55℃; for 0.5h; |
|
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With oxalyl dichloride In dichloromethane; N,N-dimethyl-formamide at 0 - 20℃; for 4h; Inert atmosphere; |
|
|
With thionyl chloride In benzene for 12h; Reflux; |
Synthesis of 1,2-13C-labeled diphenylacetyl chloride (8)
General procedure: According to the literatures,6,7 a solution of 1,2-13C-labeled diphenylacetic acid (7) (7.15 g, 33.4 mmol) and thionyl chloride (5.0 mL, 70 mmol) in dry benzene (5.0 mL) was refluxed for 12 h, and then residual thionyl chloride was removed by distillation under reduced pressures. 1,2-13C-Labeled diphenylacetyl chloride (8) (6.71 g, 28.8 mmol) was obtained as a colorless solid by distillation using a glass tube oven and recrystallization in hexane. 8 was immediately used for the next stage. |
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; for 1h; |
9.8; 10.1
[0145] 2,2-diphenylacetic acid (37 mg, 0.17 mmol) and DMF (1 drop) were added to dry dichloromethane (10 mL). After cooling to 0 °C, oxalyl chloride (27 mg, 0.21 mmol) was added, stirred at room temperature for 1 hour, and then concentrated under reduced pressure. The residue was dissolved in dichloromethane (2 mL) to obtain a 2,2-diphenylacetyl chloride solution. C283-8 (40 mg, 0.14 mmol) and triethylamine (28 mg, 0.28 mmol) were dissolved in dichloromethane (5 mL) and cooled to 0 °C. The previous 2,2-diphenylacetyl chloride solution was then slowly added. The reaction solution was allowed to react at room temperature for 5 hours. LC-MS indicated that the reaction of the starting materials was complete. Dichloromethane (30 mL) was added, washed with saturated brine (20 mL 3), dried over anhydrous sodium sulfate for 30 min and then filtered. The filtrate was concentrated under reduced pressure to obtain a crude compound. The crude product was subjected to separation by thin layer chromatography (petroleum ether:ethyl acetate=2:1) to obtain Compound C283-9 (30 mg, a colorless oily liquid, yield: 44%). MS m/z (ESI): 470.0 [M+H] +. |
|
With thionyl chloride at 100℃; |
|
|
With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 85℃; Inert atmosphere; Schlenk technique; |
|
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