| 99% |
With bis(trichloromethyl) carbonate; tetrabutylammonium bromide; potassium bromide In 1,2-dichloro-ethane at 40℃; |
5 Example 5:
In a three-necked flask, add 2-naphthol (6.63g, 0.046mmol), TBAB (7.45g, 0.023mmol), KBr (8.26g, 0.069mmol),1,2-dichloroethane (20mL), stirred at 40 °C, a solution of 1,2-dichloroethane (40 mL) of triphosgene (17.80 g, 0.060 mmol) was added to the reaction solution. After the reaction was completed, the reaction solution was washed with water. After evaporation, 10.16 g of product was obtained with a yield of 99% and a HPLC purity of 99%. |
| 99% |
With hydrogenchloride; sodium trifluoro-methanesulfinate; 1-n-hexyl-3-methylimidazol-1-ium bromide In lithium hydroxide monohydrate at 60℃; for 5h; Ionic liquid; chemoselective reaction; |
General procedures for the trifluoromethylthiolation of indole and its derivatives
General procedure: A mixture of indole (or its derivatives) 1 0.25 mmol, CF3SO2Na 2 0.30 mmol and [Hmim]Br 0.5 mL was charged in an oven-dried reaction vessel, and then concentrated HCl (37 wt.% aqueous solution, 0.5 mmol) was added followed by heating the mixture at 60 oC and stirring for 5 h. Upon completion, the reaction mixture was diluted with MTBE (4.0 mL), filtered through a bed of silica gel layered over Celite. The volatiles were removed in vacuo to afford the crude product. Further column chromatography on silica gel (EtOAc/petroleum ether) was needed to afford the pure desired products 3. |
| 99% |
With 1,3-dibromo-5,5-dimethylhydantoin In diethyl ether at 20℃; for 12h; |
|
| 98% |
With HMTAB In dichloromethane at 20℃; |
|
| 98% |
With 2,4,4,6-tetrabromo-3-n-pentadecylcyclohexa-2,5-dienone In diethyl ether at 20℃; for 0.5h; |
|
| 98% |
With NBS; lithium perchlorate; mesoporous silica In dichloromethane at 20℃; for 0.0833333h; |
|
| 98% |
With dodeca-tungstophosphoric acid; N-bromosaccharin In acetonitrile at 0℃; regioselective reaction; |
|
| 98% |
With 1,3-di-n-butyl-1H-imidazol-3-ium tribromide at 20℃; for 0.05h; Neat (no solvent); regioselective reaction; |
|
| 98% |
With N-bromosaccharin In tetrahydrofuran at 0℃; for 0.0333333h; regioselective reaction; |
|
| 98% |
Stage #1: β-naphthol With toluene-4-sulfonic acid In methanol for 0.166667h;
Stage #2: With NBS In methanol for 0.416667h; |
3.2. General Procedure for Batch Reaction Conditions in ACS-Grade Methanol
General procedure: A solution of the starting material (~10 mmol) and pTsOH (10 mol %) in MeOH (1.0 mL per mmol starting material) was stirred for 10 min, then a solution of NBS (100 mol %; recrystallized from H2O) in MeOH (0.1 M) was added dropwise over 20 min from a foiled reaction flask. The reaction mixture was stirred for a further 5 min and then concentrated in vacuo. The resultant residue was purified using column chromatography (CH2Cl2, or 1% MeOH in CH2Cl2). 3.3. Characterization of Products2-Bromo-4-methylphenol (10) [23]: 10.1 mmol; 1.73 g (92%); |
| 98% |
With 2,4,4,6-tetrabromo-3-n-pentadecylcyclohexa-2,5-dienone In diethyl ether at 20℃; for 0.5h; |
|
| 98% |
With o-xylylene bis(triethylammonium tribromide) In acetonitrile at 20℃; regioselective reaction; |
3.3. General Procedure for Bromination of AromaticCompounds
General procedure: To a magnetic solution of aromatic compound (1 mmol)in acetonitrile (5 mL), OXBTEATB (0.233 g, 0.5 mmol) wasadded and stirred at room temperature for the appropriatetime (Table 1). The reaction was monitored by TLC (eluent:n-hexane/ethyl acetate: 5/1). The reaction mixture was transferredinto a separatory funnel after filtration of OXBTEABand was extracted with water (15 mL) and dichloromethane(20 mL). The organic layer was dried over anhydrousNa2SO4, and the solvent was concentrated in a rotary evaporator.The crude product was purified by passing it over acolumn of silica gel using a mixture of n-hexane and ethylacetate as the eluent. In order to regenerate the reagent, whitesolid was treated with liquid bromine. All the product structureswere confirmed by comparison of melting point or 1HNMR spectra with ones reported in the literature [29a-29e]. |
| 97% |
With 1-butyl-3-methylpyridinium tribromide at 20℃; for 0.75h; |
|
| 97% |
With bromine; calcium bromide In acetonitrile at 25℃; for 0.0833333h; regioselective reaction; |
|
| 97% |
With hydrogen bromide; dimethyl sulfoxide In lithium hydroxide monohydrate; ethyl acetate at 60℃; for 0.166667h; |
|
| 96% |
With N-benzyl-DABCO tribromide In methanol; dichloromethane at 20℃; regioselective reaction; |
|
| 96% |
With hydrogen bromide; oxygen; NaNO2 In lithium hydroxide monohydrate; acetonitrile at 25℃; for 1h; |
|
| 95% |
With tetra-N-butylammonium tribromide In chloroform for 0.0666667h; |
|
| 95% |
With NBS In acetonitrile for 1h; Ambient temperature; |
|
| 95% |
With ethylenebis(N-methylimidazolium) bis(tribromide) In dichloromethane at 20℃; for 0.5h; regioselective reaction; |
|
| 95% |
With NBS; (Z)-N-3,5-bis(trifluoromethyl)phenyl-4-(dimethyliminio)pyridine-1(4H)-carbimidothioate In dichloromethane at 25℃; for 36h; Darkness; regioselective reaction; |
|
| 94% |
With 4,4-dibromo-5-methyl-2,4-dihydro-3H-pyrazol-3-one In glacial acetic acid for 20h; Ambient temperature; |
|
| 94% |
With hydrogen bromide; sodium bromide In chloroform; lithium hydroxide monohydrate at 0℃; Electrochemical reaction; |
|
| 94% |
With hydrogen bromide; 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo-[2.2.2]octane bis(tetrafluoroborate) In lithium hydroxide monohydrate at 20℃; for 0.166667h; regioselective reaction; |
II. Bromination of anilides 1
General procedure: 1a as example: To a stirred suspension of N-(p-tolyl)acetamide 1a (75 mg, 0.5 mmol) and Selectfluor (213 mg, 0.6 mmol) in water (3.0 mL) was added HBr (40% aqueous, 0.08 mL, 0.55 mmol), and the mixture was stirred for 5 min at room temperature. After 1a was consumed, as indicated by TLC, the reaction mixture was quenched with saturated aqueous Na2S2O3 (2.0 mL) and water (20.0 mL), and extracted with CH2Cl2 (10.0 mL) three times. The residue obtained after evaporation of the solvent was purified by column chromatography on silica gel (petroleum ether-ethyl acetate = 6:1, v/v) to afford N-(2-bromo-4-methylphenyl)acetamide 2a as a white solid (108 mg, 95% yield). |
| 94% |
Stage #1: β-naphthol With ammonium bromide In methanol for 0.0333333h;
Stage #2: In methanol |
|
| 93% |
With tetra-N-butylammonium tribromide In methanol; dichloromethane for 0.5h; Ambient temperature; reagent 1.0 equivalent; |
|
| 93% |
With hydrogen bromide; dihydrogen peroxide In methanol at 20℃; for 15h; |
|
| 93% |
With NBS at 20℃; for 2h; regioselective reaction; |
|
| 93% |
With aluminum tri-bromide; [bis(acetoxy)iodo]benzene In acetonitrile at 23℃; |
|
| 93% |
With NBS; methyl 2-pentyl-indole-3-carboxylate In n-heptane at 23℃; for 24h; Darkness; Green chemistry; regioselective reaction; |
|
| 93% |
With potassium peroxodisulfate; sodium bromide In toluene at 80℃; for 1h; |
|
| 93% |
With dimethyl sulfoxide; ethylene dibromide at 20℃; for 4h; |
|
| 92% |
With N-octylquinolinium tribromide at 20℃; for 4h; |
|
| 92% |
With potassium bromide In acetonitrile at 20℃; for 2h; |
|
| 92% |
With trimethylsilyl bromide; 4,4’-dichlorodiphenyl sulfoxide In acetonitrile at 25℃; for 6h; Inert atmosphere; regioselective reaction; |
|
| 92% |
Stage #1: β-naphthol With bromine; glacial acetic acid at 0℃; for 0.333333h; Inert atmosphere;
Stage #2: With dihydrogen peroxide In lithium hydroxide monohydrate at 15℃; for 2h; Inert atmosphere; |
Synthesis of compound 4.
(1) To a solution of naphthalen-2-ol (9.99 g, 69.4 mmol) in glacial acetic acid (90 mL)was added Br2 (2.5 mL, 48.7 mmol) in glacial acetic acid (36 mL) dropwise under N2 at 0 °C. The reaction mixture was stirred for further 20 min, then H2O2 (30%, 1.8 g) was added, allowed the reaction mixture stirred for 120min at 15 °C. After the complete consumption of the starting material, the reaction mixture was poured into 1.2 Lof H2O, massive precipitation was emerged. The reaction mixture was stirred for further 30 min and then filtrated, the filtrate cake was washed with H2O (50 mL × 3). The solid residue was dried at 45 °C for 12 h and gave 1-bromo-2-naphthol C as a gray solid (14.24 g, 92%). |
| 91% |
Stage #1: β-naphthol With toluene-4-sulfonic acid In lithium hydroxide monohydrate; acetonitrile at 20℃; for 0.0833333h;
Stage #2: With NBS In lithium hydroxide monohydrate; acetonitrile at 20℃; for 2h; regioselective reaction; |
|
| 91% |
With NBS; C28H28Se2(2+)*2BF4(1-) In 1,2-dichloro-ethane at 23℃; for 24h; Darkness; |
|
| 90% |
With NBS In Carbon tetrachloride at 25℃; for 4h; Irradiation; |
|
| 90% |
With aluminum(III) oxide; NBS at 45℃; for 0.0833333h; |
|
| 90% |
With benzyltriphenylphosphonium peroxodisulfate; potassium bromide In acetonitrile for 5.5h; Heating; |
|
| 90% |
With hydrogen bromide; dihydrogen peroxide In lithium hydroxide monohydrate at 20℃; for 8h; Darkness; |
|
| 90% |
With N-benzyl-N,N-dimethyl anilinium peroxodisulfate; potassium bromide In acetonitrile for 5.5h; Reflux; regioselective reaction; |
|
| 90% |
With 1,4-bis(3-methylimidazolium-1-yl)butane ditribromide In acetonitrile at 20℃; for 0.833333h; Green chemistry; regioselective reaction; |
|
| 90% |
With 1,2-ethanediylbis(triphenylphosphonium) ditribromide In methanol; dichloromethane at 20℃; for 0.0833333h; regioselective reaction; |
General procedure for bromination of anilines orphenols in the presence of mixture solvents
General procedure: To a mixture of anilines or phenols (0.7 mmol) the brominatingagent (1) (0.72 g, 0.7 mmol) in dichloromethane(30 ml)-methanol (15 ml) was added. The reactionmixture was stirred at room temperature until decolorizationof the orange solution took place. The progress of thereaction was monitored by TLC (eluent: n-hexane/ethylacetate, 7:3). After completion of the reaction, the solventwas evaporated and diethyl ether (10 ml) was added to theresidue. The supernatant was decanted and the insolubleresidue was washed by ether (3 × 10 ml). The combinedether extracts were dried on magnesium sulfate and also evaporated under vacuum to afford monobromo anilines ormonobromo phenols which was purified by flash columnchromatography over silica gel (n-hexane/ethyl acetate,7:3). |
| 90% |
With ferric(III) chloride; NBS; 1-n-butyl-3-methylimidazolium bistrifluoromethylsulfonylamide at 40℃; for 1h; regioselective reaction; |
|
| 90% |
With trimethylsilyl bromide; 4,4’-dichlorodiphenyl sulfoxide In acetonitrile at 0℃; for 6h; Inert atmosphere; |
13 Example 13 Preparation of 1-bromo 2-naphthol by 2-naphthol and trimethylbromosilane
2-naphthol was added sequentially to the tubular reactor (72.0 mg, 0.50 mmol), trimethylbromosilane (84.2 mg, 0.55 mmol, 1.1 equiv.), di-(4-chlorophenyl)sulfoxide (148.5 mg, 0.55 mol) and acetonitrile (1.0 mL), it was then evacuated, protected with nitrogen and reacted at 0 ° C for 6 h. After the reaction was monitored by GC-MS, it was filtered, and the filter cake was washed with a small amount of cold acetonitrile. The recovered filter cake was bis-(4-chlorophenyl)sulfide (102.8 mg). 1M sodium hydroxide (0.6 mL) was added to the filtrate, then transferred to a sep. funnel and extracted with ethyl acetate 5 mL*3. After spinning, it is combined with the above-mentioned filter cake bis-(4-chlorophenyl) sulfide.a mixture of bis-(4-chlorophenyl) sulfoxide (remaining reaction) and bis-(4-chlorophenyl)sulfide (reacted by reaction), The mixture is then completely converted to bis-(4-chlorophenyl)sulfoxide via oxidation. It can be used as a bromination reaction of the next phenol compound as an activator (total recovery is 90%). The obtained aqueous phase was extracted, and 1 M diluted hydrochloric acid was added to adjust the pH to 1, then add ethyl acetate 5 mL*3 again to extract and combine the organic phases.Dry over anhydrous sodium sulfate, spin dry to product 1-bromo 2-naphthol, The isolated yield was 90% (product purity > 97%) (selectivity 99/1). |
| 90% |
With glacial acetic acid; potassium bromide In lithium hydroxide monohydrate; glacial acetic acid at 35℃; regioselective reaction; |
4.2. General Procedure for the Bromination
General procedure: 0.11 g (1.0 mmol) of 4-methylphenol, 5 mL of acetic acid, 0.5 mL of water, and 0.12 g (1.0 mmol)potassium bromide were placed in round-bottomed flask. Then, 0.19 g (0.2 mmol)ZnAl-BrO3--LDHs was added in the flask under stirring at 35 °C. After the addition, stirring wascontinued to the end of reaction (monitored by thin layer chromatography). The residualZnAl-BrO3--LDHs were removed by centrifugation. The product was extracted with 3 × 10 mLdichloromethane. The combined extract was washed with sodium sulfite solution, brine, and dried(Na2SO4). Evaporation of the solvent left the crude product. The crude product was purified bycolumn chromatography over silica gel (ethyl acetate-petroleum ether) to obtain pure product. |
| 89% |
With sulfuric acid; sodium bromide at 60℃; for 2h; |
|
| 89% |
With polyethylene glycol entrapped potassium tribromide In neat (no solvent) for 0.166667h; Green chemistry; |
The bromination reactions were carried out in solvent free manner. In a typical reaction, PEG·KBr3 (1mmol, 4.3g) was added to the aromatic substrate (1mmol) in a mortar and was ground for the desired reaction time. The progress of the reaction was monitored by TLC (10% ethyl acetate/hexane). After completion of the reaction, the product was extracted with ethyl acetate and evaporated under vacuum to obtain the pure brominated product. The products were characterized by IR and NMR spectra (see Supporting information). |
| 89% |
With NBS In acetonitrile at 20℃; for 12h; Inert atmosphere; |
1.1 Synthesis of intermediate product (M-1)
50.0 g (437.9 mmol) of naphthalene-2-ol and 77.9 g (437.9 mmol) of N-bromosuccinimide (NBS) were added to 600 mL of acetonitrile in a 1000 mL flask, Lt; / RTI & gt; at room temperature. The resulting mixture was added to 3000 mL of distilled water, and the crystallized solid was filtered. The resulting solid was dissolved in 1,2-dichloromethane and filtered through silica gel / celite. An organic solvent was removed in an appropriate amount and then recrystallized from methanol to obtain Intermediate M- 1 (87.1 g, 89% yield). |
| 89% |
With NBS; ammonium acetate In acetonitrile at 20℃; |
|
| 89% |
With potassium (aquo)(2‑chlorobenzoato)oxodiperoxo–tungstate(VI) dihydrate; potassium bromide In lithium hydroxide monohydrate; acetonitrile at 20℃; |
Bromination of organic substrates and productanalysis
General procedure: In a representative procedure, organic substrates (1.0 mmol)were added to a solution of acetonitrile/water (1:1, 8 cm3)containing KBr (2 mmol). An accurately weighed amount ofcompound 2 (1.0 mmol) was added to the reaction mixtureat room temperature with continuous stirring. Stirring wascontinued for a further period of ca. 4-5 h. The completionof the reaction was monitored by thin-layer chromatography(TLC). The reaction products as well as the unreactedorganic substrates were separated by column chromatography.The reaction products were analyzed by GC-MS usingbenzophenone as internal standard. |
| 85% |
With pyridinium bromochromate In glacial acetic acid |
|
| 85% |
With ammonium bromide; potassium monopersulfate triple salt In methanol at 20℃; |
|
| 84% |
With N-bromophthalimide; mercury (II) acetate; glacial acetic acid In lithium hydroxide monohydrate at 20℃; |
|
| 82% |
With 2,4-diamino-1,3-thiazole hydrotribromide In glacial acetic acid Ambient temperature; Yields of byproduct given. Title compound not separated from byproducts; |
|
| 82% |
With sodium perborate; potassium bromide In glacial acetic acid at 20℃; for 2.5h; |
|
| 80% |
With NBS; 1,3-di-n-butylimidazolium tetrafluoroborate at 28 - 35℃; for 0.0833333h; |
|
| 80% |
With potassium dichromate||potassium bichromate||K2Cr2O7||Cr2O7K2; glacial acetic acid; copper (II) bromide at 20℃; for 0.5h; |
|
| 80% |
With copper (II) bromide In acetonitrile at 20℃; for 12h; |
|
| 80% |
With NBS; ammonium acetate In acetonitrile at 20℃; for 4h; |
1.1 Preparation of 1-bromo-2-naphthol
17 g (117.91 mmol) of 2-naphthol, 182 mg (2.36 mmol) of ammonium acetate was dissolved in 200 mL of acetonitrile,After the addition of 22.04 g (123.81 mmol) of N-bromosuccinimide slowly under ice bath, the system was allowed to warm to room temperatureThe reaction was carried out for about 4h, and the crude product was purified by column chromatography to obtain 1-bromo-2-naphthol in 80% yield. |
| 79% |
Stage #1: β-naphthol In acetonitrile at 80℃; for 0.166667h;
Stage #2: With NBS In acetonitrile at 80℃; for 8h; regioselective reaction; |
|
| 79% |
With hydrogen bromide In lithium hydroxide monohydrate; dimethyl sulfoxide at 60℃; for 24h; |
1-bromonaphthalen-2-ol (2)1
The reaction of naphthalen-2-ol 1 (72.1 mg, 0.5 mmol), 48%aqueous HBr solution (168.6 mg, 1 mmol) a in DMSO (1 mL) at 60 °C for 24 h, affords 88.1 mg (79%) of 4a as a white solid. |
| 78% |
With NBS In dichloromethane Irradiation; |
|
| 76% |
With tetrabutylammonium bromide; dihydrogen peroxide; vanadium pentoxide In lithium hydroxide monohydrate; acetonitrile at 5℃; for 1h; |
|
| 72% |
With NBS In acetonitrile at 20℃; |
|
| 65% |
With 1,4-diaza-bicyclo[2.2.2]octane; ethyl 2-bromoisobutyrate; dimethyl sulfoxide at 130℃; |
2. General procedure for bromination of phenyl ethers
General procedure: To a mixture of compound 1 (0.4 mmol, 1 equiv) and DABCO (0.4 mmol, 1 equiv) in DMSO (2.0 mL) was added ethyl bromoisobutyrate 2 (2.0 mmol, 5 equiv). The resulting reaction mixture was stirred at 130°C without exclusion of air until complete consumption of compound 1 (monitored by TLC). Then the reaction mixture was cooled to rt, diluted with DCM, and washed with water. The organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified directly by a silica gel flash chromatography (Hexane/EtOAc) to give compound 3. |
| 63% |
With NBS; N,N-dimethyl-formamide; trichlorophosphate at -5 - 39.84℃; for 0.666667h; |
|
| 60% |
With NBS at 35℃; for 0.0333333h; |
|
| 55% |
With dihydrogen peroxide; molibdic acid; potassium bromide for 0.5h; Heating; |
|
| 50% |
With NBS; lithium hydroxide monohydrate; C20H29NO7 at 23℃; for 24h; Sealed tube; Darkness; |
|
| 42% |
With sodium bromide In lithium hydroxide monohydrate; acetonitrile at 20℃; for 2.5h; Electrochemical reaction; |
|
| 40% |
With ammonium metavanadate; dihydrogen peroxide; potassium bromide In lithium hydroxide monohydrate; acetonitrile for 48h; Ambient temperature; pH 5; |
|
|
With bromine; glacial acetic acid Licht; |
|
|
With sulfuric acid; bromine; glacial acetic acid |
|
|
With bromine; glacial acetic acid |
|
|
With 1,4-dioxane; bromine |
|
|
With bromine; anhydrous sodium carbonate |
|
|
With aluminum amalgam; bromine; glacial acetic acid |
|
|
With bromine In glacial acetic acid |
|
|
bromination; |
|
|
With sodium hydroxide; bromine 1) MeOH, 2) MeOH, 0-5 deg C, 1 h; ambient temperature, 20 min; Multistep reaction; |
|
|
With NBS; zirconium tetrachloride In dichloromethane at 20℃; for 2h; |
|
| 97 % Chromat. |
With 4DABCO*6HBr*4Br2; mesoporous silica In dichloromethane at 20℃; for 0.0333333h; |
|
|
With NBS In acetonitrile at 30℃; for 0.05h; UV-irradiation; |
|
|
With NBS In dichloromethane at -78 - 20℃; for 2 - 3h; |
6
Bromination using NBS has been found to be applicable for use with a wide range of aromatic starting materials or substrates, as is EPO summarized in Table 1 . For example, anisole can be brominated by use of 1 equivalent of NBS in the presence of 5 mol % of ZrCI4 at -78 0C to afford p- bromoanisole in 98% yield as sole product (Table 1 , Entry 1 ). However, in the absence of ZrCI4 the halogenation does not proceed, even at room temperature (Table 1 , Entry 1 ).[00111] All of the substrates shown in Table 1 were brominated to give the corresponding monobromo products in excellent yield and regioselectivity. In most cases, the reaction can proceed at very low temperature and no further purification is necessary. In addition. Table 1 reveals that the halogenation of the present invention is compatible with a variety of substituents.Table 1 ZrCI4 Catalyzed Bromination of Aromatic Compounds EPO (5 mol %), CH2CI2 (4d See spectroscopic data for characterization. |
| 99 %Chromat. |
With oxone; ammonium bromide In methanol at 20℃; for 0.75h; regioselective reaction; |
|
| 100 %Spectr. |
With dihydrogen peroxide; glacial acetic acid; potassium bromide In lithium hydroxide monohydrate at 60℃; for 2h; regioselective reaction; |
|
| 94 %Chromat. |
With potassium peroxomonosulfate; ammonium bromide In methanol; lithium hydroxide monohydrate at 20℃; for 0.0333333h; Green chemistry; regioselective reaction; |
|
| 99 %Chromat. |
With dihydrogen peroxide; ammonium bromide; glacial acetic acid In lithium hydroxide monohydrate for 20h; Green chemistry; |
|
|
With potassium(carbonato)oxodiperoxotungstate(VI)monohydrate; potassium bromide In lithium hydroxide monohydrate; acetonitrile at 20℃; for 1h; |
|
|
With pyridinium hydrobromide perbromide In acetonitrile at 0℃; |
|
|
With NBS In N,N-dimethyl-formamide at 0 - 5℃; for 0.333333h; |
1.1 1) Synthesis of 1-bromo-2-naphthol (Synthesis of 1-bromo-2-naphthol by reaction of 2-naphthol and NBS in a solvent):
Add 144.2 g of 2-naphthol (1 mol) and 280 ml of DMF (dimethylformamide) to a 1000 ml reaction flask, stir evenly (mixing time is about 10 minutes), cool down to 0-5 ° C, then add dropwise Adding time is about 20-30 minutes) 178g NBS (N-bromosuccinimide, 1mol), using a water bath to control the temperature of the solution in the reaction flask does not exceed 5 ° C, after the addition is 0-5 ° CThe reaction was kept for 20 minutes. At this time, by HPLC, the starting material 2-naphthol was less than 1%.Add 500 ml of water to the liquid in the reaction flask, quench (the reaction is finished), add 200 ml of toluene, layer, the organic layer is in the upper layer, transfer the organic layer to the pear-shaped separatory funnel, and repeat the toluene extraction operation once. Adding 100 ml of water to the organic layer liquid in the pear-shaped separatory funnel for extraction, removing the water layer (lower layer), and repeating the water extraction operationThen, the organic layer solution was transferred to a spherical bottle of a rotary evaporator, kept at 60-70 ° C until the toluene was no longer distilled off, and lowered to room temperature, and 200 ml of DMF was added to the spherical bottle for use. The solution at this time was a mixture of 1-bromo-2-naphthol and DMF.The mixture contained 0.992 mol of 1-bromo-2-naphthol, so the atomic conversion rate in this step was as high as 99.2%. |
|
With bromine; glacial acetic acid at 0℃; for 0.5h; |
2. General Procedure for Aryne Precursors 1a-1m
The synthesis of compound 1a was examplified. A solution of phenol (1.00 g, 10.63 mmol) and Br2 (0.49 mL, 9.56 mmol) in AcOH (7 mL) was stirred for 30 min at 0 °C, the reaction mixture was poured into a separatory funnel with ice water (10 mL) and the aqueous phase was extracted with DCM (3 × 15 mL). The combined organic extracts were washed with saturated NaCl (aq) and dried over MgSO4 and concentrated under reduced pressure. The crude product was dissolved in THF (15 mL) and added to HMDS (2.44 mL, 11.69 mmol) for reflux at 70 °C for 2 h. The solvent was evaporated under reduced pressure and the crude product was dissolved in THF (15 mL). Finally, the solution was cooled to -78 °C and n-BuLi (5.53 mL, 2.5 M, 13.82 mmol) was added dropwise and stirred for 1 h. Tf2O (1.97 mL, 11.69 mmol) was added dropwise and was stirred for 1.5 h. Cold saturated aqueous NaHCO3 (20 mL) was added after separation, and the aqueous layer was extracted with Et2O. The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography to give 1a. The remaining compounds 1b-1m (structures showed in Figure 1) were obtained by the same synthetic route. |
|
With bis(trichloromethyl) carbonate; tetrabutylammonium bromide; potassium bromide In lithium hydroxide monohydrate; ethyl acetate at 20℃; for 19h; regioselective reaction; |
4-Bromo-1-methoxybenzene (2a).
General procedure: To the solution of anisole (0.50 g, 4.6 mmol), TBAB (0.75 g, 2.3 mmol), KBr (0.83 g, 6.9 mmol), ethyl acetate (3.0 mL) and water (0.050 g, 2.8 mmol) were added and stirred at room temperature. A solution of BTC (1.78 g, 6.0 mmol) in ethyl acetate (6.0 mL) was dropwised to the reaction mixture. After the reaction finished, the reaction mixture was washed with water (10 mL × 2) and evaporated. The product was obtained with 99% purity by HPLC. 1 H NMR (400 MHz, DMSO-d6, ppm): δ 7.46-7.42 (m, 2H), 6.78-6.76 (m, 2H), 3.74 (s, 3H). |
|
With NBS In Carbon tetrachloride at 0 - 20℃; for 3h; |
|
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