|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane Heating; |
|
|
With thionyl chloride In chloroform at 40℃; for 3h; |
|
|
With thionyl chloride In chloroform |
|
|
With thionyl chloride In benzene for 1h; Heating; |
|
|
With phosphorus pentachloride |
|
|
With thionyl chloride In benzene |
|
|
With pyridine; thionyl chloride |
|
|
With thionyl chloride In benzene for 3h; Heating; |
|
|
With oxalyl dichloride In dichloromethane |
|
|
|
15.a (a)
(a) 4-(1-phenylmethanoyl)benzoyl chloride In a manner similar to Example 9(a), starting with 500 mg (2.2 mmol) of 4-benzoylbenzoic acid, 490 mg (91%) of the expected product are obtained in the form of a white solid. |
|
With thionyl chloride In <i>N</i>-methyl-acetamide; tetramethylsilane; toluene |
1 Preparation of 4-Benzoylbenzoyl Chloride (BBA-Cl) (Compound I)
Example 1 Preparation of 4-Benzoylbenzoyl Chloride (BBA-Cl) (Compound I) 4-Benzoylbenzoic acid (BBA), 1.0 kg (4.42 moles), was added to a dry 5 liter Morton flask equipped with reflux condenser and overhead stirrer, followed by the addition of 645 ml (8.84 moles) of thionyl chloride and 725 ml of toluene. Dimethylformamide, 3.5 ml, was then added and the mixture was heated at reflux for 4 hours. After cooling, the solvents were removed under reduced pressure and the residual thionyl chloride was removed by three evaporations using 3*500 ml of toluene. The product was recrystallized from 1:4 toluene:hexane to give 988 g (91% yield) after drying in a vacuum oven. Product melting point was 92-94° C. Nuclear magnetic resonance ("NMR") analysis at 80 MHz (1H NMR (CDCl3)) was consistent with the desired product: aromatic protons 7.20-8.25 (m, 9H). All chemical shift values are in ppm downfield from a tetramethylsilane internal standard. The final compound (Compound I shown below) was stored for use in the preparation of a monomer used in the synthesis of photoactivatable polymers as described, for instance, in Example 3. |
|
With thionyl chloride In <i>N</i>-methyl-acetamide; tetramethylsilane; toluene |
1 Preparation of 4-Benzoylbenzoyl Chloride (BBA-C1) (Compound I)
Example 1 Preparation of 4-Benzoylbenzoyl Chloride (BBA-C1) (Compound I) 4-Benzoylbenzoic acid (BBA), 1.0 kg (4.42 moles), was added to a dry 5 liter Morton flask equipped with reflux condenser and overhead stirrer, followed by the addition of 645 ml (8.84 moles) of thionyl chloride and 725 ml of toluene. Dimethylformamide, 3.5 ml, was then added and the mixture was heated at reflux for 4 hours. After cooling, the solvents were removed under reduced pressure and the residual thionyl chloride was removed by three evaporations using 3*500 ml of toluene. The product was recrystallized from 1:4 toluene:hexane to give 988 g (91 % yield) after drying in a vacuum oven. Product melting point was 92-94° C. Nuclear magnetic resonance (NMR) analysis at 80 MHz (1H NMR (CDCl3)) was consistent with the desired product: aromatic protons 7.20-8.25 (m, 9H). All chemical shift values are in ppm downfield from a tetramethylsilane internal standard. The final compound was stored for use in the preparation of a monomer used in the synthesis of photoactivatable polymers as described, for instance, in Example 3. |
|
With thionyl chloride In <i>N</i>-methyl-acetamide; tetramethylsilane; toluene |
3.a (a)
(a) Preparation of 4-Benzoylbenzoyl Chloride (BBA-Cl) 4-Benzoylbenzoic acid (BBA), 1 kg (4.42 moles), was added to a dry 5 liter Morton flask equipped with reflux condenser and overhead stirrer, followed by the addition of 645 ml (8.84 moles) of thionyl chloride and 725 ml of toluene. Dimethylformamide, 3.5 ml, was then added and the mixture was heated at reflux for 4 hours. After cooling, the solvents were removed under reduced pressure and the residual thionyl chloride was removed by three evaporations using 3*500 ml of toluene. The product was recrystallized from toluene/hexane (1/4 by volume) to give 988 g (91% yield) after drying in a vacuum oven. Product melting point was 92-94° C. Nuclear magnetic resonance (NMR) analysis at 80 MHz (1H NMR (CDCl3)) was consistent with the desired product: aromatic protons 7.20-8.25 (m, 9H). All chemical shift values are in ppm downfield from a tetramethylsilane internal standard. The final compound was stored for use in the preparation of a monomer used in the synthesis of photoactivatable polymers as described, for instance, in Example 3(c) or for heterobifunctional compounds as described, for instance, in Example 1(a). |
|
With thionyl chloride In toluene |
1.A A.
A. Synthesis of 4-Benzoylbenzoyl Chloride (BBA-Cl) 4-Benzoylbenzoic acid (BBA), 200.0 g (0.884 moles), was added to a dry 2 liter round bottom flask, followed by the addition of 273 ml of thionyl chloride. Dimethylformamide (DMF), 684 ul, was then added and the mixture was refluxed for 3-4 hours. After cooling, the excess thionyl chloride was removed on a rotary evaporator at water aspirator pressure. Any remaining thionyl chloride was removed by repeated evaporation with 3*100 ml of toluene. The final product was then recrystallized from 5:1 hexane: toluene with typical yields of BBA-Cl at >90% and a melting point of 92-94° C. |
|
With thionyl chloride |
R.36 4-(Benzoyl)benzoyl Chloride
Reference Example 36 4-(Benzoyl)benzoyl Chloride The conditions to prepare Reference Example 34 are used with 2.0 g of 4-benzoylbenzoic acid and 30 ml of thionyl chloride to give the desired product in a solution of 30 ml of methylene chloride. |
|
With pyridine; thionyl chloride |
3.a (a)
(a) Synthesis of 4-benzoyl-benzoyl chloride 12.7 ml (0.175 mol) of thionyl chloride and a few drops of pyridine are added to 8 g (0.035 mol) of 4-benzoyl-benzoic acid. The reaction mixture is heated to reflux temperature (about 80°C) and is kept at said temperature until the reaction is complete (i.e., until the evolution of hydrogen chloride has ceased). Thus 8 g of acyl chloride are obtained. The crude reaction product is purified by crystallization from 1:1 ether/pentane. |
|
With thionyl chloride In <i>N</i>-methyl-acetamide; tetramethylsilane; toluene |
A A.
A. Preparation of 4-Benzoylbenzoyl Chloride (BBA-Cl) The compound 4-Benzoylbenzoic acid (BBA), 1.0 kg (4.42 moles), was added to a dry 5 liter Morton flask equipped with reflux condenser and overhead stirrer, followed by the addition of 645 ml (8.84 moles) of thionyl chloride and 725 ml of toluene. Dimethylformamide, 3.5 ml, was then added and the mixture was heated at reflux for 4 hours. After cooling, the solvents were removed under reduced pressure and the residual thionyl chloride was removed by three evaporations using 3*500 ml of toluene. The product was recrystallized from 1:4 toluene:hexane to give 988 g (91% yield) after drying in a vacuum oven. Product melting point was 92-94° C. Nuclear magnetic resonance (NMR) analysis (1H NMR (CDCl3)) was consistent with the desired product: aromatic protons 7.20-8.25 (m, 9H). All chemical shift values are in ppm downfield from a tetramethylsilane internal standard. The final compound was stored for use in the preparation of a monomer used in the synthesis of APMA-HCl below. |
|
With oxalyl dichloride |
|
|
With oxalyl dichloride |
75.A
Example 75 10-(4-BENZOYLBENZOYL)-N-(PYRIDIN-3-YLMETHYL)-10,11-DIHYDRO-5H-PYRROLO[2,1-C][1,4]BENZODIAZEPINE-3-CARBOXAMIDE Step A. Phenyl[4-(5H-pyrrolo[2,1-c][1,4]benzodiazepin-10(11H)-ylcarbonyl)phenyl]methanone; To solution of 10,11-dihydro-5H-pyrrolo[2,1-c][1,4]benzodiazepine (0.807 g, 4.38 mmol) in dry dichloromethane (20 mL) cooled in an ice bath was added N,N-diisopropylethyl amine (1.14 mL). The solution was treated dropwise with a suspension of 4-benzoylbenzoyl chloride (prepared from 3 mmol of 4-benzoylbenzoic acid and oxalyl chloride) in 8 mL of dichloromethane. The solution was stirred overnight at room temperature, diluted with dichloromethane, washed with water, 1 N hydrochloric acid, saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and evaporated to dryness. The residue was flash chromatographed over silica gel Merck-60 with a solvent gradient of 5 to 20% of ethyl acetate in hexane to provide the title compound (1.2 g) as a crystalline solid. MS [(+)ESI, m/z]: 393.12 [M+H]+ |
|
With thionyl chloride for 2h; Reflux; |
1-(4-Benzoyl)benzoyl-3-thiosemicarbazide (3i)
A solution of 4-benzoylbenzoic acid (0.565 g, 2.50 mmol) in thionyl chloride (5 ml) was heated under reflux for 2 h to convert it to its acid chloride. Excess thionyl chloride was evaporated at reduced pressure, then the residue was dissolved in toluene (5 ml) and evaporated at reduced pressure until dry (x2). The acid chloride was added portionwise to a stirred chilled (0 °C) suspension of thiosemicarbazide 2 (0.228 g, 2.50 mmol) in dry pyridine (5 ml) and stirring was overnight at room temperature. The reaction mixture was poured in water (100 ml) with stirring. Stirring was continued for further 2 h until the oily precipitate formed had solidified completely. The solid was then filtered off and recrystallised from aqueous acetic acid. |
|
With thionyl chloride for 2h; Reflux; |
General Procedure: The carboxylic acid (1equiv) was refluxed with excess of thionyl chloride for 2 h. The excess of thionyl chloride was evaporated at reduce pressure. The residue was dissolved in toluene (5 mL) and evaporated at reduce pressure until dryness two times. The crude acid chloride was dissolved in acetone. This solution was treated at 0 °C with (+)-6-aminopenicillanic acid (6-APA, 1.5 equiv) dissolved into a 2% NaHCO3/water solution (50 ml), diluted with acetone (40 ml). After stirring at room temperature for 2-4 h, the reaction mixture was washed with ethyl acetate (25 ml). The aqueous layer was poured into ethyl acetate (50 ml) and acidified with a 0.1M HCl/water solution to pH 2-3. The organic phase was washed three times with water and dried with anhydrous Na2SO4. The organic layer was concentrated by evaporating the solvent at reduced pressure and triturated with petroleum ether and ethyl acetate or dichloromethane to give the title compounds. |
|
With oxalyl dichloride; N,N-dimethyl-formamide In 1,4-dioxane for 0.75h; |
1 Synthesis of 4-Benzoyl Benzoic Acid Choride From 4-Benzoyl Benzoic Acid
To a solution of 4-benzoyl benzoic acid (2.26 g, 10 mmol, Aldrich) in anhydrous 1,4-dioxane (20 mL) was added oxalyl chloride (1.76 mL, 20 mmol), followed by dimethylformamide (4 drops). After 45 minutes the mixture was concentrated to dryness under vacuum. The 4-benzoyl benzoic chloride acid produced was crystallized from 30 mL of 1:4 toluene/hexane. The solid 4-benzoyl benzoic chloride was rinsed with hexane and dried under vacuum to afford a white crystalline solid (1.26 g; melting point 92-92° C). |
| 1.26 g |
With oxalyl dichloride; N,N-dimethyl-formamide In 1,4-dioxane for 0.75h; |
1 Synthesis of 4-Benzoyl Benzoic Acid Chloride From 4-Benzoyl Benzoic Acid
To a solution of 4-benzoyl benzoic acid (2.26 g, 10 mmol, Aldrich) in anhydrous 1,4-dioxane (20 mL) was added oxalyl chloride (1.76 mL, 20 mmol), followed by dimethylformamide (4 drops). After 45 minutes the mixture was concentrated to dryness under vacuum. The 4-benzoyl benzoic chloride acid produced was crystallized from 30 mL of 1:4 toluene/hexane. The solid 4-benzoyl benzoic chloride was rinsed with hexane and dried under vacuum to afford a white crystalline solid (1.26 g; melting point 92-92° C.). |
|
With oxalyl dichloride In dichloromethane at 20℃; for 2h; |
|
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; |
14
Example 14: 4-benzoyl-N-(6-methoxybenzo[d]thiazol-2-yl)benzamide. 4-benzoyl benzoic acid (500 mg, 2.2 mmol) was suspended in methylene chloride (5 ml) and the resulting mixture was treated with DMF (20 μ) and oxalyl chloride (0.93 ml, 11 mmol). The mixture was stirred at room temperature until gas evolution ceased and a clear solution resulted, about 1 h. The solvent was removed and the resulting solid was fused with 6-methoxybenzo[d]thiazol-2-amine (397 mg, 2.2 mmol) in the manner described in Example 15 to give the title compound (779 mg, 91%) as a solid: 1H NMR (400 MHz, Chloroform-d) δ 11.77 (s, 1H), 8.19 (d, J= 8.1 Hz, 2H), 7.86 (d, J= 8.1 Hz, 2H), 7.76 (d, J= 7.6 Hz, 2H), 7.59 (t, J= 7.4 Hz, 1H), 7.53 (d, J= 8.8 Hz, 1H), 7.47 (t, J= 7.6 Hz, 2H), 7.30 (d, J= 2.6 Hz, 1H), 6.98 (dd, J= 8.9, 2.5 Hz, 1H), 3.85 (s, 3H); LCMS (ESI) m/z 386.1 [M- 1]" |
|
With phosphorus pentachloride In chloroform at 0℃; for 0.75h; Inert atmosphere; |
|
| 1.03 g |
With thionyl chloride In N,N-dimethyl-formamide; toluene for 120h; Reflux; |
Synthesis of 4-benzylbenzoyl chloride (96)
4-benzyl benzoic acid (1 g, 4.42 mmol) was added to a dry flask along with thionyl chloride (3 mL), DMF (0.5 mL) and toluene (13 mL). The flask was heated under reflux for 5 days. The solvent was removed under reduced pressure and the product was re-dissolved in toluene (5 mL) twice and the solvent removed. The product was dried under vacuum at room temperature under vacuum to give a white solid. Yield = 1.03 g NMR (CDCh) δ ppm:8.56, 8.54, 8.29, 8.24, 8.24, 8.23, 8.21, 8.20, 8.20, 8.19, 8.18, 7.93, 7.90, 7.89, 7.88, 7.87, 7.86, 7.86, 7.85, 7.84, 7.82, 7.81, 7.80, 7.80, 7.78, 7.78, 7.77, 7.67, 7.66, 7.65, 7.64, 7.63, 7.62, 7.62, 7.61, 7.60, 7.60, 7.59, 7.58, 7.54, 7.53, 7.52, 7.50, 7.50, 7.49, 7.48, 7.47, 7.47, 7.24, 6.82, 3.95, 3.47, 3.33, 2.15, 1.79, 0.217.83 - 7.73 (m, 2H)„ 7.96 - 7.80 (m, 2H), 8.30 - 8.13 (m, 2H), lH NMR (250 MHz, Chloroform-d) δ 7.69 - 7.56 (m, 1H), 7.50 (tt, = 6.6, 1.5 Hz, 2H). MS (+APCI) m/z= Found 245.0366; calculated for Ci4Hi0CliO2245.0364; 0.9 ppm |
|
With thionyl chloride for 1.5h; Reflux; |
5.11 General procedure for the preparation of acyl chlorides
General procedure: A mixture of thionyl chloride (2.0mL, 3.6g, 30mmol) and the corresponding carboxylic acid (3mmol) was refluxed for 1.5h. Excess thionyl chloride was removed by distillation. The residue obtained was co-evaporated with toluene (3×5mL) in vacuo to ensure the complete removal of thionyl chloride. The acyl chloride product was used without further purification in the next step. |
|
With thionyl chloride; N,N-dimethyl-formamide In toluene at 75℃; for 4h; Sealed tube; |
|
|
With 1-pyrrolidinecarboxaldehyde; 1,3,5-trichloro-2,4,6-triazine |
|
|
With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 20℃; for 12h; Schlenk technique; Inert atmosphere; |
|
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; Inert atmosphere; |
|
|
With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 0 - 20℃; |
Acyl chlorides
General procedure: The acid (5 mmol) was dissolved in anhydrous CH2Cl2 (10 mL) and DMF (a few drops) added.Oxalyl chloride (6 mmol, 1.2 equiv.) was added dropwise to the solution, that was cooled in an icewater bath. The resulting mixture was allowed to stir at room temperature for an additional 4 h andthe solvent was evaporated to afford the crude acyl chloride, which was used directly in the nextstep. |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
