Structure of 606-25-7
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CAS No. : | 606-25-7 |
Formula : | C10H9NO2S |
M.W : | 207.25 |
SMILES Code : | O=S(C1=C2C=CC=CC2=CC=C1)(N)=O |
MDL No. : | MFCD00985933 |
InChI Key : | ZFIFHAKCBWOSRN-UHFFFAOYSA-N |
Pubchem ID : | 163571 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H302-H315-H319-H335 |
Precautionary Statements: | P261-P305+P351+P338 |
* 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 |
---|---|---|
96.7% | With ammonium hydroxide; In acetone; at 0℃; | 1-naphthalenesulfonyl chloride (5 g, 21.9 mmol) was added to a 1 L round bottom flask containing 200 ml of acetone, stirred, In the ice bath drop 240ml 0C of ammonia, dripping finished, the thin layer tracking test reaction, the reaction is completed, Vacuum distillation of organic solvents and ammonia decomposition of ammonia, precipitation of solid, filtration, vacuum drying, To give 1-naphthalenesulfonamide (4.35 g, yield 96.7%). The compound was used in the next step without further purification. The experimental data are as follows: |
96.7% | With ammonium hydroxide; In acetone; at 0℃; | Add 1-naphthalenesulfonyl chloride (5g, 21.9mmol) into a 1L round-bottomed flask containing 200ml of acetone, stir, and add 240ml of ammonia at 0C in an ice bath. After the addition is complete,Thin layer tracking detection reaction, after the reaction is completed,Distill under reduced pressure to remove the ammonia gas from the decomposition of organic solvents and ammonia water, and precipitate solids.Filter and vacuum dry to obtain 1-naphthalenesulfonamide (4.35 g, yield 96.7%). This compound does not require further purification and is directly used in the next reaction. |
96.7% | With ammonium hydroxide; In acetone; at 0℃; | Add 1-naphthalenesulfonyl chloride (5g, 21.9mmol) into a 1L round-bottomed flask containing 200ml of acetone, stir, and add 240ml of ammonia water at 0C in an ice bath. After the addition is complete, the reaction will be traced and detected by a thin layer. After the reaction is completed, the organic solvent and the ammonia gas decomposed by the ammonia water are distilled off under reduced pressure, and the solid is separated out, filtered, and dried under vacuum to obtain 1-naphthalenesulfonamide (4.35 g, yield 96.7%). This compound does not require further purification and is directly used in the next reaction. The experimental data are as follows |
96.7% | With ammonia; In acetone; at 0℃; | Add 1-naphthalenesulfonyl chloride (5g, 21.9mmol) into a 1L round-bottomed flask containing 200ml of acetone, stir, and add 240ml of ammonia water at 0C in an ice bath. After the addition is complete, the reaction will be tracked by a thin layer. After the reaction is completed, the organic solvent and the ammonia gas decomposed by the ammonia water are distilled off under reduced pressure, and the solid is precipitated, filtered, and dried under vacuum to obtain 1-naphthalenesulfonamide (4.35 g, yield 96.7%). |
91.8% | With ammonium hydroxide; In acetone; at 20℃; for 3h; | 1-naphthalenesulfonyl chloride (1 , 50 g) was stirred with 28 % ammonium hydroxide (300 ml_) in acetone (1 L) at room temperature for about 3 h, then the reaction mixture was concentrated by rotary evaporation at about 60 C (water bath) to 500 ~ 600 ml_, cooled to room temperature, and 1.5 L of water was added slowly while stirring. Then the formed white precipitate was filtered and washed with 2 L of water. After dried by air, 42 g of white powder 1-naphthalenesulfonamide (2) was obtained in the yield of 91.8%. |
90.2% | With ammonium hydroxide; In acetone; at 0 - 20℃; for 3.08333h; | Synthetic procedure of naphthalene-5,8-dione-1-sulfonamide: naphthalenesulfonylchloride (16.8 g, 74.3 mmol) was dissolved in acetone (100 mL) and was stirred at 0 C for 5 min. Ammonium hydroxide (100 mL) was dropped into the above mixture and stirred at room temperature for 3 h. Precipitated white crystals were filtered then acetone was removed at reduced pressure. The residue was washed in ethyl acetate (3×10 mL), producing a white solid powder, which was used without further purification, yielding naphthalenesulfonamide (15.9 g, 90.2%); mp (147-149 C). |
90.2% | With ammonium hydroxide; In acetone; at 0 - 25℃; for 3h; | a. PREPARATION OF NAPHTHALENESULFONAMIDE [00458] The structure of naphthalenes is shown below: [00459] Naphthalenesulfonylchloride (16.8 g, 74.3 mmol) was dissolved in acetone (100 mL) and was stirred at 0 C for 5 minutes. Ammonium hydroxide (100 mL) was dropped into the above mixture and stirred at room temperature for 3 hours. Precipitated white crystals were filtered then acetone was removed at reduced pressure. The residue was washed in ethylacetate (3 x 10 mL), producing a white solid powder which was used without further purification, yielding naphthalenesulfonamide (15.9 g, 90.2%); mp (147-149 C). |
82.1% | With ammonium hydroxide; In acetone; at 0 - 20℃; for 3.5h; | [0091 ] Synthesis of Compound 2:; Naphthalene sulfonyl chloride (compound 1 ) ( 1 g, 4.41 mmol) was dissolved in acetone (52 ml) and was stirred at 0C for 30 mins. Ammonium hydroxide (52 ml) was cooled to 0"C and was added to the above mixture and stirred at room temperature for 3 hrs. The acetone was then removed at reduced pressure. The residue was dissolved in dichloromethane (100 ml) and washed with water (2 x 100 ml). The organic layer was collected and evaporated under reduced pressure. The residue was purified by silica column chromatography (hexane EtOAc, 3: 1 ) yielding compound 2 (750 mg, 82.1 %); m.p 147-149C (lit. 150C). |
42 g | With ammonium hydroxide; In acetone; at 20℃; for 3h; | Firstly, 1-naphthalenesulfonyl chloride (1, 50 g; what does it mean? 50 g?) was stirred with 28% ammonium hydroxide (300 mL) in acetone (1 L) at rt for about 3 h, concentrated, cooled to rt (room temperature, filtered, washed and dried by air, 42 g of white powder 1-naphthalenesulfonamide (2) was obtained. Secondly, the compound 2 (48 g) was dissolved completely suspended in acetic acid (480 mL) and then cooled to 40 ~ 45C, and CrO3 (104 g) solution in H2O (100 mL) and acetic acid (100 mL) was added in 1 ~ 1.5 h, which was then stirred, filtered,washed and dried by air to obtainthe crude product (24 g). 48g crude product was dissolved in minimum acetone at rt and hexane was added slowly till precipitate was just observed, then place it in refrigerator (about -20C) overnight. Filtration afforded 26.9 g of compound 3. Thirdly, the compound 3 (15.45 g) was dissolved in CH2Cl2 (1.2 L) and methanol (162 mL) at rt, then cooled to -20 ~ -15C and Et3N (1.54 mL) was added. After stirringfor about 15 min, 3-hydroxy-1-pyrone (8.74 g) in 300 mL of CH2Cl2 was added and stirred for about 30 min, then 2 ~ 3 h at rt. The formed yellow precipitate was collected by filter to getthe first crop of LLL12 (3.24 g). Filtrate was concentrated at 33C by rotary evaporation underhose vacuum to 150 ml. Add 250 ml CH2Cl2 to precipitate, filter and wash with small quantityCH2Cl2 to get 2nd crop of LLL12(5.27g). Further purification by silica gel flash column chromatographyeluted with mixed solvents of acetone and hexanes (1:1, V/V) afforded 3.95 g ofLLL12. Finally, LLL12 (2.01 mg) was suspended in pyridine (15 g) at rt, then dimethycarbamylchloride (1.02 g) was added and stirred at rt overnight. Then the reaction mixtures were filteredand washed with CH2Cl2 and then large quantity of acetone (about 1 L) to afford the compound of LLL12B. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With 1,8-diazabicyclo[5.4.0]undec-7-ene; 1,1'-carbonyldiimidazole; | In the same manner as in Example 141, 0.390 g of 1-(2-chlorobenzyl)-2-methyl-6-(1-naphthalenesulfonylcarbamoyl)benzimidazole sodium salt (207) were formed from 0.600 g of 6-carboxy-1(2-chlorobenzyl)-2-methylbenzimidazole, 0.647 g of N,N'-carbonyldiimidazole, 0.829 g of <strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> and 0.608 g of diazabicycloundecene. Properties of Compound (207): 1H-NMR(DMSO-d6, δ): 2.46(3H, s), 5.49(2H, s), 6.39(1H, d, J=7.8 Hz), 7.16(1H, t, J=7.5 Hz), 7.31(1H, t, J=7.3 Hz), 7.36(1H, t), 7.40-7.45(2H, m), 7.50(1H, t, J=7.7 Hz), 7.54(1H, d, J=8.0 Hz), 7.75-7.81(2H, m), 7.87(1H, d, J=7.9 Hz), 7.93(1H, d, J=8.2 Hz), 8.09(1H, d, J=7.3 Hz), 8.86(1H, d, J=8.5 Hz). IR(KBr): 1633 cm-1. Mass(FAB): m/e 512(M+1). mp: ~265 C.(decomp.) |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
86.1% | With triethylamine; In tetrahydrofuran; | EXAMPLE 11 Naphthalenesulfonamide, 5-(dimethylamino)-N-(2-bromoethyl) A suspension of 5-dimethylaminonaphthalene-1-sulfonyl chloride (50.0 g, 0.185 mol) and 2-bromoethylamine hydro-bromide (40.4 g, 0.197 mol) in THF (500 mL) was cooled to 2 C. A solution of triethylamine (38.5 g, 0.380 mol) in THF (250 mL) was added dropwise over a 2 h period while maintaining the internal temperature below 6 C. After complete addition the mixture was stirred at ambient temperature for 17 h. The mixture was clarified then concentrated to an orange oil which was chromatographed over silica (2.2 kg) packed and eluted with hexanes-EtOAc (3:1). Fractions (500 mL) containing the purified product were combined, clarified, then concentrated to a damp solid. This material was triturated in hexanes (250 mL), collected on a filter, washed with hexanes (50 mL) then dried to constant weight in vacuo at 40 C. to give 56.9 g (86.1% yield) of product as a off-white crystalline solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With diaza-bicyclo-undecene; 1,1'-carbonyldiimidazole; | EXAMPLE 100 Production of 3-(2,4-dichlorobenzyl)-2-methyl-5-((1-naphthalene)sulfonylcarbamoyl)indole (130) According to the method of Example 59, obtained is 3-(2,4-dichlorobenzyl)-2-methyl-5-(1-naphthalenesulfonylcarbamoyl)indole (130) (0.191 g) from 5-carboxy-3-(2,4-dichlorobenzyl)-2-methylindole (0.334 g), N,N'-carbonyldiimidazole (0.243 g), <strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> (0.331 g) and diazabicycloundecene (0.228 g). 1H-NMR (DMSO-d6, δ ppm): 2.27 (3H, s), 4.06 (2H, s), 6.85 (1H, d, J=8.4 Hz), 7.21 (1H, dd, J=2.2 and 8.3 Hz), 7.27 (1H, d, J=8.6 Hz), 7.48 (1H, dd, J=1.7 and 8.6 Hz), 7.60 (2H, m), 7.63 (1H, d, J=2.2 Hz), 7.72 (1H, t, J=7.8 Hz), 7.94 (1H, s), 8.08 (1H, m), 8.28 (1H, d, J 8.3 Hz), 8.36 (1H, d, J=7.4 Hz), 8.69 (1H, m), 11.35 (1H, s), 12.50 (1H, brs). IR (Nujol): 1693 cm-1. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With diaza-bicyclo-undecene; 1,1'-carbonyldiimidazole; | EXAMPLE 142 Synthesis of 1-(2-chlorobenzyl)-2-methyl-6-(1-naphthalenesulfonylcarbamoyl)benzimidazole sodium salt (207) In the same manner as in Example 141, 0.390 g of 1-(2-chlorobenzyl)-2-methyl-6-(1-naphthalenesulfonylcarbamoyl)benzimidazole sodium salt (207) were formed from 0.600 g of 6-carboxy-1-(2-chlorobenzyl)-2-methylbenzimidazole, 0.647 g of N,N'-carbonyldiimidazole, 0.829 g of <strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> and 0.608 g of diazabicycloundecene. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93% | In dichloromethane; | To a solution of 2-naphthalene sulfonyl chloride (3 g, 13.23 mmol) and serine benzylester (3.07 g, 13.23 mmol) in 120 mL CH2 Cl2 was added Et3 N (5.53 mL, 13.23 mmol) at 0 C. The reaction was stirred at room temperature for 1 hr and washed with a saturated (sat.) solution of KHSO4, brine, and dried over Na2 SO4. The organic layer was concentrated in vacuo to give the naphthylsulfonamide (93%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
13.1 g (90%) | With triethylamine; In tetrahydrofuran; ethanol; | a. 2-Ethoxalylamino-6-(N-ethoxalyl)sulfamoylnaphthalene To a solution of 7.7 g (34.7 mmol) 2-amino-6-sulfamoylnaphthalene in 250 ml dry tetrahydrofuran was added 21.0 ml (0.15 mol) dry triethylamine, and then dropwise 17.0 ml (0.15 mol) ethoxalylchloride. Stirring was continued at 25C for 24 h. The reaction mixture was filtered and evaporated in vacuo . The residue was stirred with ethanol to give 13.1 g (90%) 2-ethoxalylamino-6-(N-ethoxalyl)sulfamoylnaphthalene, m.p. 191C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | With potassium carbonate; In butanone; | EXAMPLE 8 5,6-Dihydroxy-2-[4-(1-naphthylsulfonylaminocarbonylamino)thien-3-yl]pyrimidine-4-carboxylic Acid (630) A mixture of 1-naphthalene sulfonamide (769 mg, 3.67 mmol) and potassium carbonate (563 mg, 4.07 mmol) in 2-butanone (9 ml) was heated under reflux for 30 min. Ethyl chloroformate (430 mg, 3.96 mmol) was added dropwise and the resulting solution was heated under reflux for 3 h. The mixture was cooled and diluted with H2O (30 ml) and AcOEt (10 ml). The aqueous layer was collected and adjusted to pH 2 by addition of 1N HCl (aq). Extraction with AcOEt (2*20 ml) and concentration of the dried organic extracts afforded ethyl 1-naphthylsulfonylcarbamate (674 mg, 67%) as a white solid. 1H NMR (DMSO-d6): δ 12.35 (bs, 1H), 8.57 (1H, d, J 8.6), 8.29 (2H, m), 8.11 (1H, d, J 7.7), 7.71 (3H, m), 3.90 (2H, q, J 7.1), 0.99 (3H, t, J 7.1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58.43% | With cerium(IV) sulphate; sulfuric acid; acetic acid; In water; at 65℃; for 0.45h; | Dissolve anhydrous cerium sulfate (160g, 677.45mmol) with 750ml 2mol/L dilute sulfuric acid,The temperature is controlled at 65C. Add <strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> (10g, 48.49mmol) into a 500ml round bottom flask containing 200ml of glacial acetic acid, control the temperature at 65C, and stir at this temperature.Slowly add dropwise to the cerium sulfate aqueous system, start timing from the dropwise addition,Monitoring by thin layer chromatography, the reaction was stopped after 27 minutes, and after the reaction solution was cooled, Filter, extract the filtrate with 1200ml of dichloromethane, dry and remove water, and then rotate under low pressure.A light yellow solid was obtained, which was dried under vacuum,5,8-dioxo-dihydronaphthalene (6.72 g, yield 58.43%) was obtained. It is directly used in the next reaction without purification. |
58.43% | With cerium(III) sulfate; sulfuric acid; acetic acid; at 65℃; for 0.45h; | The anhydrous cerium sulfate (160g, 677.45mmol) was dissolved in 750ml of 2mol/L dilute sulfuric acid, and the temperature was controlled at 65C.Add <strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> (10g, 48.49mmol) into a 500ml round bottom flask containing 200ml of glacial acetic acid, control the temperature at 65C, stir at this temperature, and slowly add dropwise to the cerium sulfate aqueous system. Start timing, TLC monitoring, and stop the reaction after 27 minutes. After the reaction solution is cooled, filter, and extract the filtrate with 1200ml of dichloromethane, dry and remove water, and then rotate at low pressure to obtain a pale yellow solid, which is dried in vacuum to obtain 5, 8 -Dioxo-dihydronaphthalene (6.72 g, yield 58.43%). It is directly used in the next reaction without purification. The experimental data are as follows: |
58.43% | With cerium(IV) sulphate; sulfuric acid; acetic acid; In water; at 65℃; for 0.45h; | The anhydrous cerium sulfate (160g, 677.45mmol) was dissolved in 750ml of 2mol/L dilute sulfuric acid, and the temperature was controlled at 65C. . Add <strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> (10g, 48.49mmol) into a 500ml round bottom flask containing 200ml of glacial acetic acid, control the temperature at 65C, and stir at this temperature. Slowly add dropwise to the cerium sulfate aqueous system, start timing from the dropwise addition, Monitoring by thin layer chromatography, the reaction was stopped after 27 minutes, and after the reaction solution was cooled, Filter, extract the filtrate with 1200ml dichloromethane, After drying and removing water, low-pressure rotary evaporation is obtained to obtain a light yellow solid, which is dried in vacuum. 5,8-dioxo-dihydronaphthalene (6.72g, yield 58.43%) was obtained. |
19% | With chromium(VI) oxide; In water; acetic acid; at 90℃; for 0.3h;Reflux; | Naphthalenesulfonamide (500 mg, 2.41 mmol) was dissolved in slowly warming glacial acetic acid (5.0 mL). The mixture was heated to 90 C and chromium trioxide (1.08 g, 10.85 mmol), which was dissolved in a mixture of water and glacial acetic acid (3 mL, v/v: 1/1), and added to the mixture solution. The above solution was stirred under reflux for 18 min and quenched with iced water (50 mL). The solution was cooled to 0 C and stirred 1 h at room temperature. The precipitated yellow powder was filtered and the remaining solution was extracted with ether (3×100 mL). The organic layer was collected, dried, and removed at reduced pressure. The yellow powder was combined and purified with silica column chromatography ethyl acetate/hexane (v/v: 2/3) to yield 1 (110 mg, 19%); mp (186-188 C). |
19.3% | b. PREPARATION OF 5,8-DIOXO-5,6,7,8-TETRAHYDRONAPHTHALENE-1- SULFONAMIDE (COMPOUND 1) [00460] The structure of 5,8-dioxo-5,6,7,8-tetrahydronaphthalene-l-sulfonamide (Compound 1) is shown below: [00461] The numbering scheme for Compound 1 is shown below: [00462] 5,8-dioxo-5,6,7,8-tetrahydronaphthalene-l-sulfonamide was synthesized as previously described (Lin, L., et al. Int. J. cancer. 2012, 130, 1459-69) with some modifications; procedures are shown in Scheme 1. Naphthalenesulfonylchloride reacted with ammonium hydroxide at room temperature, precipitated white crystal <strong>[606-25-7]naphthalenesulfonamide</strong> with high purity ready for next step synthesis and 90.2% yield. Naphthalenesulfonamide was oxidized by chromium trioxide in an acidic environment. This reaction is highly time sensitive, since the longer reaction times result in more byproducts. To achieve the optimal reaction time, the solvent can be preheated to reflux, and then add chromium trioxide into the reaction system. 5H-naphth[l,8-c<i]isothiazol-5-one, 1, 1-dioxide was not very stable during the column separation, so flash column was used for purification. SCHEME 1 [00463] Naphthalenesulfonamide (500 mg, 2.41 mmol) was dissolved in slowly warming glacial acetic acid (5.0 mL). The mixture was heated to 90 C and chromium trioxide (1.08 g, 10.85 mmol), which was dissolved in a mixture of water and glacial acetic acid (1 : 1 v/v, 3 mL), was added to the mixture solution. The above solution was stirred under reflux for 18 minutes. The solution was cooled to 0 C and water (50 mL) was added and stirred overnight at room temperature. The precipitated yellow powder was filtered and the remaining solution was extracted with ether (3x 100 mL). The organic layer was collected, dried, and removed at reduced pressure. The yellow powder was combined and purified with silica column chromatography ethyl acetate-hexane (2:3 v/v) to yield the desired sulfonamide (1 10 mg, 19.3%); mp (186-188 C). | |
17.48% | With chromium(VI) oxide; acetic acid; In water; at 85℃; | <strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> (0.5 g, 2.4 mmol) was added to a 25 ml round bottom flask containing 5 ml of glacial acetic acid, controlled at 85C, Chromium trioxide (1.09 g, 10.9 mmol) was dissolved in 1 ml of water and 1ml of glacial acetic acid, Slowly drip into the system, from the start of the drip, 16 minutes after the reaction, the reaction solution into 80ml ice water containing 100ml beaker quenching, standing overnight, precipitation of light yellow solid, filtration, vacuum drying, 5,8-dioxo-<strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> (100 mg, yield 17.48%). Directly used for the next reaction without purification |
15.4% | With chromium(VI) oxide; acetic acid; In water; for 0.25h;Reflux; | [0092] Synthesis of Compound 3:; Compound 2 (500 mg, 2.41 mmol) was dissolved in glacial acetic acid (5.0 ml). Chromium trioxide ( 1.08 g, 10.85 mmol) was dissolved in a mixture of water/glacial acetic acid ( 1 : 1 , 2 ml) and added to the solution of compound 2 in glacial acetic acid and was stirred under reflux for 15 mins. The solution was cooled to 0C and water (25 ml) was added and the resulting solution was stirred overnight at room temperature. The reaction mixture was diluted with water (500 ml) and extracted with ether (3 x 100 ml). The organic layer was collected and dried under reduced pressure and purified with silica column chromatography ethyl acetate/hexane (2:3) to yield compound 3 (88 mg, 15.4%); m.p ( 187-188C); 1 H NMR (300 MHz, DMSO) δ 7.23 (2H, d, J = 9 Hz), 7.43 (2H, S), 8.1 1 ( 1 H, t, J = 9 Hz), 8.34 ( 1 H, d, J= 9 Hz), 8.515 ( 1 H, d, J=9 Hz). ([M+Na]+ 260.7). |
With chromium(VI) oxide; acetic acid; In water; at 20 - 45℃; | The compound 2 (24 g) was suspended in acetic acid (300 mL) and was heated to dissolved completely, then cooled to 40 ~ 45 C (water bath), and CrC (52 g) solution in H2O (50 mL) and acetic acid (50 mL) was added over 1 ~ 1.5 h and the water bath temperature was maintained around 42 C. After the addition, the reaction mixture was stirred for additional 2 h at room temperature. Then 1 L of water was added and filtered. The obtained yellow solid was washed with large amount of water and dried by air. H NMR spectrum of the crude product indicated that it contained about 50 % of starting material 2 besides the desired 5,8- dioxo-5,8-dihydro<strong>[606-25-7]naphthalene-1-sulfonamide</strong> (3). (0264) [0240] The crude product (36 gm from 6 batch reactions) was dissolved in minimum acetone at room temperature and hexane was added till precipitate was just observed, then place it in refrigerator (about -20 C) overnight. Filtration afforded 13.6 g of compound 3 with purity of 93 %, the final yield was about 8.3 %. | |
With chromium(VI) oxide; acetic acid; In water; at 40 - 45℃; | Firstly, 1-naphthalenesulfonyl chloride (1, 50 g; what does it mean? 50 g?) was stirred with 28% ammonium hydroxide (300 mL) in acetone (1 L) at rt for about 3 h, concentrated, cooled to rt (room temperature, filtered, washed and dried by air, 42 g of white powder <strong>[606-25-7]1-<strong>[606-25-7]naphthalenesulfonamide</strong></strong> (2) was obtained. Secondly, the compound 2 (48 g) was dissolved completely suspended in acetic acid (480 mL) and then cooled to 40 ~ 45C, and CrO3 (104 g) solution in H2O (100 mL) and acetic acid (100 mL) was added in 1 ~ 1.5 h, which was then stirred, filtered,washed and dried by air to obtainthe crude product (24 g). 48g crude product was dissolved in minimum acetone at rt and hexane was added slowly till precipitate was just observed, then place it in refrigerator (about -20C) overnight. Filtration afforded 26.9 g of compound 3. Thirdly, the compound 3 (15.45 g) was dissolved in CH2Cl2 (1.2 L) and methanol (162 mL) at rt, then cooled to -20 ~ -15C and Et3N (1.54 mL) was added. After stirringfor about 15 min, 3-hydroxy-1-pyrone (8.74 g) in 300 mL of CH2Cl2 was added and stirred for about 30 min, then 2 ~ 3 h at rt. The formed yellow precipitate was collected by filter to getthe first crop of LLL12 (3.24 g). Filtrate was concentrated at 33C by rotary evaporation underhose vacuum to 150 ml. Add 250 ml CH2Cl2 to precipitate, filter and wash with small quantityCH2Cl2 to get 2nd crop of LLL12(5.27g). Further purification by silica gel flash column chromatographyeluted with mixed solvents of acetone and hexanes (1:1, V/V) afforded 3.95 g ofLLL12. Finally, LLL12 (2.01 mg) was suspended in pyridine (15 g) at rt, then dimethycarbamylchloride (1.02 g) was added and stirred at rt overnight. Then the reaction mixtures were filteredand washed with CH2Cl2 and then large quantity of acetone (about 1 L) to afford the compound of LLL12B. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
73% | With silver hexafluoroantimonate; dichloro(pentamethylcyclopentadienyl)rhodium (III) dimer; [bis(acetoxy)iodo]benzene; In 1,2-dichloro-ethane; at 80℃; for 16h; | General procedure: In air, a 10 mL of dried Schlenk tube was charged with azoxybenzene (1a; 79.2 mg, 0.40 mmol), TsNH2 (2a; 102.6 mg, 0.60 mmol), [Cp*Rh- Cl2]2 (3.1 mg, 0.005 mmol), AgSbF6 (13.7 mg, 0.04 mmol), and PhI(OAc)2 (193.2 mg, 0.60 mmol). Then the freshly distilled 1,2-dichloroethane (1.0 mL) was injected into the Schlenk tube. The reaction tube was placed in an oil bath and stirred at 80 C for 16 h; then it was cooled to r.t. and the reaction completion was checked by TLC. H2O (10.0 mL) was subsequently added to the reaction mixture and extracted with CH2Cl2 (3 5.0 mL). The organic layers were combined, dried (MgSO4), and concentrated under reduced pressure to yield the crude product, which was further purified by flash chromatography (silica gel, PE/EtOAc 9:1 → 5:1, v/v), affording the product 3a as a pale yellow solid (120.4 mg, 0.33 mmol, 82%); |