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CAS No. : | 827-94-1 | MDL No. : | MFCD00007639 |
Formula : | C6H4Br2N2O2 | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | N/A |
M.W : | 295.92 g/mol | Pubchem ID : | - |
Synonyms : |
|
Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P280 | UN#: | N/A |
Hazard Statements: | H302+H312+H332 | Packing Group: | N/A |
GHS Pictogram: |
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* 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 |
---|---|---|
93% | With sulfuric acid; sodium nitrite; In ethanol; for 3.25h;Heating / reflux; | To a suspension of 2,6-dibromo-4-nitroaniline (75.0 g, 254 mmol) in ethanol (1 L) was added H2SO4 (100 mL). The mixture was heated to reflux and sodium nitrite (50.5 g, 730 mmol) was added portion-wise over a period of 15 min. The mixture was heated at reflux for 3 h and was then cooled to room temperature. The formed thick suspension was poured on ice water (1000 mL) upon which more solid precipitated. The solid was filtered and the filter cake washed with water (2×250 mL) and dried in an oven at 20 mbar/30 C. to give 66.2 g (93%) of 1,3-dibromo-5-nitrobenzene as a brown solid. |
93% | Example 11,3-Dibromo-5-nitrobenzene(The named compound was synthesized according to Dumont, Bull. Soc. Chim. Bel., 505 (1995). This compound is also commercially available from Karl Industries, Aurora, Ohio.) To a suspension of 2,6-dibromo-4-nitroaniline (75.0 g, 254 mmol) in ethanol (1 L) was added H2SO4 (100 mL). The mixture was heated to reflux and sodium nitrite (50.5 g, 730 mmol) was added portion-wise over a period of 15 min. The mixture was heated at reflux for 3 h and was then cooled to room temperature. The formed thick suspension was poured on ice water (1000 mL) upon which more solid precipitated. The solid was filtered and the filter cake washed with water (2×250 mL) and dried in an oven at 20 mbar/30 C. to give 66.2 g (93%) of 1,3-dibromo-5-nitrobenzene as a brown solid. | |
93% | With ethanol; sulfuric acid; sodium nitrite; for 3.25h;Heating / reflux; | Soc. CMm. Bel., 505 (1995). This compound is also commercially available from Karl Industries, Aurora, OH.) To a suspension of 2,6-dibromo- 4-nitroaniline (75.0 g, 254 rnmol) in ethanol (1 L) was added H2SO4 (100 mL). The mixture was heated to reflux and sodium nitrite (50.5 g, 730 mmol) was added portion- wise over a period of 15 min. The mixture was heated at reflux for 3 h and was then cooled to room temperature. The formed thick suspension was poured on ice water (1000 mL) upon which more solid precipitated. The solid was filtered and the filter cake washed with water (2x250 mL) and dried in an oven at 20 mbar/30C to give 66.2 g (93%) of l,3-dibromo-5-nitrobenzene as a brown solid. |
90% | Step 1. 1,3-Dibromo-5-nitro-benzene.To an ice-cold solution of 2,6-dibromo-4-nitro-aniline (100 g, 0.34 mol) in 1.50 L of ethanol was added dropwise cone. H2SO4 (116 ml, 2.15 mol) over 30-45 min with constant stirring. The reaction mixture was heated to 600C and sodium nitrite (72 g, 1.09 mol) was added to the reaction mixture portion wise. The resulting yellow colored reaction mixture was heated slowly to 900C and refluxed for 2 to 2.5 h. After cooling to room temperature, the mixture was poured into ice water. The reddish brown solid thus obtained was filtered, washed with water and dried to give the desired compound as a brown solid (85.0 g, 90%). 1H-NMR (400 MHz, DMSOd6): delta 8.38 (d, J= 1.20 Hz, 1 H) and 8.40 Hz1 br s, 2H). | |
79% | With sulfuric acid; sodium nitrite; In ethanol; at 90℃; for 36h; | In a round bottom flask 2,6-dibromo-4-nitroaniline (29.0 g, 97.73 mmol) were dissolved in 300 mL of ethanol and 35 mL sulfuric acid (conc.). The solution was heated to 90 C. To the solution NaNO2 (21.8 g, 316.1 mmol, 3.23 eq.) was added in small portions and then heated for additional 36 h. The cooled solution was added to ice water. The resulting solid crude product was filtered and washed with water. After recrystallization in ethanol the product was filtered, washed with small portions of ethanol and dried in vacuum overnight (Yield: 21.6 g, 79%). 1H-NMR (CDCl3, 500 MHz): delta (in ppm): 7.98 (t, 4J1,3 = 1.5 Hz, 1 H, 1-H), 8.31 (d, 4J3,1 = 1.5 Hz, 2 H, 3-H). 13C-NMR (CDCl3, 125 MHz): delta (in ppm): 123.43 (Cq, C-2), 125.58 (CH, C-3), 140.03 (CH, C-1), 148.89 (Cq, C-4). |
47% | With sulfuric acid; sodium nitrite; In ethanol; at 90℃; for 30h; | 1,3-dibromo-5-nitrobenzene (30) To a stirred, boiling (90 C.) mixture of 2,6-dibromo-4-nitroaniline (1 g, 3.38 mmol), ethanol (12 mL) and concentrated sulfuric acid (2 mL), sodium nitrite (0.75 g, 10.88 mmol) was added in portions as rapidly as foaming would permit. The reaction mixture was stirred at 90 C. for 30 h. The mixture was allowed to cool, poured into ice water and the solids were collected by filtration and washed with water. The 3,5-dibromobenzene was separated from the remaining inorganic salts by dissolving it in boiling ethanol and filtering the hot solution, from which 0.457 g (47% yield) of the product (30) crystallized on cooling: 1H-NMR (400 MHz, CDCl3) delta 8.32 (d, J=1.6 Hz, 2H), 8.00 (t, J=1.6 Hz, 1H). |
41% | With sulfuric acid; sodium nitrite; In water; ethyl acetate; at 50 - 55℃; for 0.166667h; | Step B: 3,5-Dibromonitrobenzene; NaN02 (4.1 g, 59.1 mmol) was added portionwise to a solution of 2,6-dibromo- 4-nitroaniline (5 g, 3.5eq) in 20% H2S04 and AcOEt (each 40 mL) at a rate to keep the internal temperature at 50-55^. After heating for an additional 10 min, the mixture was cooled, diluted, and extracted with AcOEt . The combined organic layers were dried over Na2S04, filtered and evaporated. The residue was purified by flash chromatography (cyclohexane/ DCM//7/3 then 8/2) to yield expected compound as a white solid (1 .94 g, 41 % yield).H NMR (300 MHz, CDCI3) 5 8.32 (d, J = 1 .8 Hz, 2H), 8.00 (t, J = 1 .8 Hz, 1 H). |
2.23 g | With isopentyl nitrite; In N,N-dimethyl-formamide; at 50℃; for 0.166667h; | To a solution of 4-nitroaniline 2g (14.5 mmol, 1eq) in 30 mL of AcOH was added dropwise 1,62 mL (31.9 mmol, 2.2 eq) of bromine and the resulting mixture was stirred at 50 oC overnight. The resulting precipitate was filtered by suction on a glass frit, washed with H2O and dry under vacuum. The solid was then added by portion to a hot (50 oC) stirred solution of isoamyle nitrite 10 mL in 10 mL of DMF. After 10 min the mixture was cooled to room temperature and poured into 100 mL of HCl 3N, subject to extraction with AcOEt (3 X 40 mL), dry over Na2SO4 and concentrated on a rotary evaporator. Purification of the residue by column chromatography yielded 2.23g (55 %) 9b as a yellow solid.1H NMR (CDCl3), d = 8.00 (s, 1H, CHAr); 8.30 (s, 2H, CHAr). 13C NMR (CDCl3), d = 123.8 (2C, Cq); 125.9 (2C, CHAr); 140.5 (1C, CHAr); 149.3 (1C, Cq). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: 2,6-dibromo-4-nitroaniline With hydrogen bromide; sodium nitrite In water at 0℃; for 2h; Stage #2: With urea for 0.333333h; Stage #3: With hydrogen bromide; copper(I) bromide at 0℃; for 2.25h; | |
With nitric acid Diazotization.Faellen mit Brom-Bromkalium in Bromwasserstoffsaeure und Kochen des Reaktionsprodukts mit Alkohol; | ||
With hydrogen bromide Behandeln mit Natriumnitrit; |
Diazotization.Umsetzen mit Cuprobromid; | ||
With potassium disulphite; nitric acid Behandlung des Reaktionsgemisches mit wss. Brom-KBr-Loesung und Kochen des entstandenen Perbromids mit Aethanol; | ||
Multi-step reaction with 3 steps 1: 97 percent / i-pentyl nitrite; HOAc / 0 - 5 °C 2: 94 percent / aq. NaOH / 0.5 h / 0 - 5 °C 3: 94 percent / aq. HBr / acetonitrile / 2 h / 60 °C | ||
With tert.-butylnitrite; copper(ll) bromide In acetonitrile |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 2,6-dibromo-4-nitroaniline With sulfuric acid; sodium nitrite In acetic acid at 20℃; for 4h; Stage #2: With iodine; potassium iodide In water; acetic acid at 20℃; for 12h; | |
With nitrosylsulfuric acid; sulfuric acid Diazotization.Behandlung der Diazoniumsalz-Loesung mit KI in Wasser; | ||
ueber die Diazoverbindung; |
With sulfuric acid; acetic acid Diazotization.Behandlung der Diazoniumsalz-Loesung mit KI in Wasser; | ||
Multi-step reaction with 3 steps 1: 97 percent / i-pentyl nitrite; HOAc / 0 - 5 °C 2: 94 percent / aq. NaOH / 0.5 h / 0 - 5 °C 3: 79 percent / aq. HI / acetonitrile / 13 h / 60 °C |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | Stage #1: 2,6-dibromo-4-nitroaniline With tin(ll) chloride In tetrahydrofuran; ethanol at 50℃; for 16h; Inert atmosphere; Stage #2: With sodium hydroxide In tetrahydrofuran; ethanol at 25℃; for 2.5h; Inert atmosphere; | |
95% | With hydrazine hydrate In ethanol for 2h; Heating; | |
80% | With iron; acetic acid at 20℃; Inert atmosphere; |
With hydrogenchloride; tin(ll) chloride | ||
With hydrogenchloride; tin(ll) chloride | ||
Stage #1: 2,6-dibromo-4-nitroaniline With sodium tetrahydroborate In methanol for 0.0166667h; Stage #2: With CoCu0.2Fe1.8O4 In methanol for 0.0333333h; | ||
In <i>N</i>-methyl-acetamide; ethanol; dichloromethane; ethyl acetate | XI 4-Amino-2,6-dibromoaniline EXAMPLE XI 4-Amino-2,6-dibromoaniline 20 g of 2,6-Dibromo-4-nitroaniline are taken up in 250 ml of ethanol, 250 ml of ethyl acetate, 100 ml of dimethylformamide and 90 ml of methylene chloride and, after addition of 3.3 g of 5% moist platinum/active carbon catalyst, hydrogenated at room temperature under 50 psi for one hour. The solvent is then distilled off in a rotary evaporator, and the residue is triturated with diethyl ether, filtered off with suction and washed several times with petroleum ether. Yield: 8 g (45% of theory),; Melting point: 127°-132° C.; Rf: 0.59 (silica gel; petroleum ether/ethyl acetate=10:5) | |
With hydrogen In <i>N</i>-methyl-acetamide; ethanol; ethyl acetate | XVIII 1,4-Diamino-2,6-dibromobenzene EXAMPLE XVIII 1,4-Diamino-2,6-dibromobenzene 3.0 g of 2,6-dibromo-4-nitroaniline are dissolved in 150 ml of ethanol, 150 ml of ethyl acetate and 30 ml of dimethylformamide and, after addition of 0.5 g of platinum on carbon (5%), hydrogenated under a pressure of 1.5 bar of hydrogen in a Parr apparatus at room temperature for 1 hour. Cooling is followed by filtration, the solvent is distilled off in a rotary evaporator, and the residue is purified by column chromatography. Yield: 14 g of a colourless oil, Rf: 0.47 (silica gel; petroleum ether/ethyl acetate 2:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
87% | With bromine In tetrachloromethane at 20℃; Cooling with ice; | |
With bromine; acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With bromine In acetic acid | |
98% | With N-Bromosuccinimide; lithium perchlorate; silica gel In dichloromethane at 20℃; for 0.0833333h; | |
98.7% | With hydrogenchloride; brominating reagent In dichloromethane; water at 28℃; for 0.75 - 1h; | 5 EXAMPLE 5 To 5.0 ml of dichloromethane containing 4-nitroaniline (1 g, 7.246 m mole) in a 250 ml round bottom flask, 1.45 ml of 12 N hydrochloric acid and 10 ml of deionised water were added. To this reaction mixture, brominating reagent containing (2.9 g) of brominating reagent dissolved in 20 ml of deionised water was added slowly under continuous stirring at 28° C. for a period of 30 to 45 minutes. After completion of the addition, stirring was continued for another 15 minutes. The organic layer was separated and extracted with dichloromethane. The organic layer and the organic extracts were mixed and then washed successively with sodium thiosulphate solution and brine. The product, 2,6-dibromo-4-nitroaniline was dried over anhydrous sodium sulphate and concentrated to yield 98.7%. It was characterized by melting point; NMR; IR and elemental analysis. _ |
98% | With bromine; calcium bromide In water at 25℃; for 0.333333h; regioselective reaction; | |
98% | Stage #1: 4-nitro-aniline With acetic acid at 65℃; for 0.75h; Stage #2: With bromine for 1.25h; | |
97% | With bromine In acetic acid at 65℃; for 4h; | |
95% | With hydrogen bromide; dihydrogen peroxide In methanol at 0 - 20℃; for 10h; | |
95% | With hydrogen bromide; dihydrogen peroxide In water at 20℃; for 28h; Darkness; | |
95% | Stage #1: 4-nitro-aniline With sulfuric acid In water for 0.0833333h; Green chemistry; Stage #2: With sodium bromate; sodium bromide In water at 20℃; for 4h; Green chemistry; | |
95% | With N-Bromosuccinimide In acetonitrile at 20℃; for 6h; | |
93% | With PyHBrCl2 In methanol at 20℃; for 0.0833333h; | |
93% | With hydrogenchloride; dihydrogen peroxide; sodium bromide In water at 15℃; for 2h; | |
93% | With bromine In methanol; dichloromethane at 20℃; for 2h; | |
92% | With bromine; acetic acid at 65℃; for 4h; | |
92% | With bromine In water at 20℃; for 0.166667h; | |
91% | With methanol; P-benzyltriphenylphosphonium tribromide; sodium hydrogencarbonate In dichloromethane for 0.25h; Ambient temperature; | |
90% | With iodine pentoxide; potassium bromide In water at 20℃; for 23h; regioselective reaction; | Typical Procedure for the Bromination of Aromatic CompoundsUsing I2O5-KBr in Water General procedure: A mixture of arene (0.5 mmol), I2O5 (334 mg, 1.0 mmol), and KBr (148 mg, 1.25 mmol) was dissolved in 2mL of H2O. The reaction was complete after stirring for the indicated time at room temperature. The mixture was extracted by ethyl acetate and concentrated under reduced pressure, and the mixture was purified by flash column chromatography (silica gel) to afford the desired product. |
90% | With dibromamine-T In acetonitrile at 20℃; for 0.166667h; | 2, 6-Dibromo-4-nitroaniline General procedure: TsNBr2 (1 mmol) was added at 0 C to a solution of the aromatic compound(1 mmol) in acetonitrile (2 mL). After 10 min of stirring at room temperature, sodium thiosulfate (200 mg approx.) was added and stirred for 10 min. The reaction wastaken up in ethyl acetate, dried over NaSO4, and concentrated. The crude productwas purified by flash chromatography or silica gel (230-400 mesh) with a mixtureof petroleum ether and ethyl acetate as eluent. |
89% | With bromine | |
85.2% | With bis<dimethylacetamide>hydrogen dibromobromate In ethanol; water | |
85% | With 1-benzyl-1-aza-4-azoniabicyclo<2.2.2>octane bromide; calcium carbonate In methanol at 20℃; for 0.666667h; | |
With bromine | ||
With hydrogenchloride; bromine | ||
With sulfuric acid; bromine | ||
With methanol; bromine | ||
With bromine; acetic acid | ||
With bromine; acetic acid | ||
With bromine; acetic acid for 4h; | ||
With bromine In hydrogenchloride; acetic acid for 3h; | ||
Multi-step reaction with 2 steps 1: bromine / tetrachloromethane / 4 h / 10 - 20 °C 2: bromine / tetrachloromethane / 20 °C / Cooling with ice | ||
With bromine In acetic acid at 50℃; | 3,5-dibromonitrobenzene 9b To a solution of 4-nitroaniline 2g (14.5 mmol, 1eq) in 30 mL of AcOH was added dropwise 1,62 mL (31.9 mmol, 2.2 eq) of bromine and the resulting mixture was stirred at 50 oC overnight. The resulting precipitate was filtered by suction on a glass frit, washed with H2O and dry under vacuum. The solid was then added by portion to a hot (50 oC) stirred solution of isoamyle nitrite 10 mL in 10 mL of DMF. After 10 min the mixture was cooled to room temperature and poured into 100 mL of HCl 3N, subject to extraction with AcOEt (3 X 40 mL), dry over Na2SO4 and concentrated on a rotary evaporator. Purification of the residue by column chromatography yielded 2.23g (55 %) 9b as a yellow solid.1H NMR (CDCl3), d = 8.00 (s, 1H, CHAr); 8.30 (s, 2H, CHAr). 13C NMR (CDCl3), d = 123.8 (2C, Cq); 125.9 (2C, CHAr); 140.5 (1C, CHAr); 149.3 (1C, Cq). | |
With bromine; acetic acid | ||
90 %Chromat. | With Oxone; ammonium bromide In methanol; water at 20℃; for 0.0833333h; Green chemistry; regioselective reaction; | |
With bromine; acetic acid |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
95% | With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,2-dimethoxyethane; ethanol; water for 14h; Heating; | |
94% | With potassium phosphate tribasic heptahydrate; palladium diacetate In water; N,N-dimethyl-formamide at 80℃; for 1h; | |
55% | With sodium carbonate In ethanol; benzene for 48h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | With triethylamine In benzene at 70℃; for 22h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 55 percent / aq. Na2CO3 / Pd(PPh3)4 / benzene; ethanol / 48 h / Heating 2: 48 percent / p-toluenesulfonic acid monohydrate / benzene / 40 h / Heating |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1.1: NaNO2; H2SO4; aq. H3PO4 / 2 h 1.2: urea; H2SO4; aq. H3PO4 / 20 °C 1.3: 85 percent / H2SO4; aq. H3PO4 / 0 - 20 °C 2.1: 99 percent / tin; aq. HCl / 7 h / 90 °C | ||
Multi-step reaction with 2 steps 1: 80 percent / H2SO4; NaNO2 / ethanol / 36 h / 90 °C 2: 89 percent / SnCl2*2H2O / ethanol; tetrahydrofuran / 20 h / 20 °C | ||
Multi-step reaction with 2 steps 1: 97 percent / NaNO2, H2SO4 / ethanol 2: 96 percent / 1.) H2; 2.) aq. HCl / Raney Ni / ethanol |
Multi-step reaction with 2 steps 1: 94 percent / conc. sulfuric acid, sodium nitrite / ethanol / 3 h / Heating 2: 78 percent / 1.) iron powder, acetic acid, 2.) NaOH / ethanol / 2 h / Heating | ||
Multi-step reaction with 2 steps 2: tin; hydrochloric acid | ||
Multi-step reaction with 2 steps 2: iron; diluted sulfuric acid | ||
Stage #1: 2,6-dibromo-4-nitroaniline With sulfuric acid; sodium nitrite In ethanol Stage #2: With water; tin(ll) chloride In ethanol | ||
Multi-step reaction with 2 steps 1: ethanol; sulfuric acid; sodium nitrite / 3 h / 60 - 90 °C / Cooling with ice; Inert atmosphere 2: tin(II) chloride dihdyrate / ethanol / 1.5 h / 80 °C | ||
Multi-step reaction with 2 steps 1: sodium nitrite; sulfuric acid / ethanol / 4 h / 80 °C 2: iron; ammonium chloride / water; acetone / 6 h / 80 °C | ||
Multi-step reaction with 2 steps 1: sulfuric acid; sodium nitrite / ethanol / 90 °C 2: tin(II) chloride dihdyrate / ethanol; tetrahydrofuran / 22 °C | ||
Multi-step reaction with 2 steps 1.1: sulfuric acid; sodium nitrite / ethanol / 40 h / 80 °C 2.1: tin(II) chloride dihdyrate / methanol; tetrahydrofuran / 20 h / 60 °C 2.2: 2 h | ||
Multi-step reaction with 2 steps 1.1: sulfuric acid / ethanol / 0.5 - 0.75 h / 0 °C 1.2: 2 - 2.5 h / 60 - 90 °C / Heating / reflux 2.1: tin(ll) chloride / ethanol / 1.5 h / 20 - 80 °C / Heating / reflux 2.2: pH 12 |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
55.5% | With sodium acetate; sodium nitrite In dichloromethane; chloroform; phosphorus pentoxide; acetic acid | 5.c c c 4-[(2,6-dibromo-4-nitrophenyl)azo]-2-octadecyloxy-1-naphthol 22.7 g (0.33 mol) sodium nitrite are fed into 300 ml concentrated sulphuric acid in a 2 l three-neck flask with stirrer, Claisen attachment and thermometer during 10-15 minutes while stirring whereby the temperature of the reaction solution is allowed to increase to 35° C. It is then cooled to 20° C. and 230 ml glacial acetic acid are added dropwise in ca. 15-20 minutes in such a way that the temperature is held at 20°-25° C. while cooling on ice. Afterwards 97.6 ml (0.33 mol) 2,6-dibromo-4-nitroaniline (Riedel de Haen [99% GC] are added in portions during 10 minutes while cooling occasionally whereby the temperature is kept at 19°-21° C. and it is stirred again for a further 3 hours. Afterwards it is poured onto 3.5 l iced water and the diazonium salt solution which forms is added rapidly to a solution of 124 g (0.3 mol) 2-octadecyloxy-1-naphthol in a mixture of 3 l glacial acetic acid and 300 ml chloroform with addition of 180 g (1.33 mol) sodium acetatetrihydrate. (In the production of the solution of the naphthol ether care must be taken that after it has been fed into glacial acetic acid/chloroform with addition of sodium acetate it is again cooled down to 20° C. after a temperature increase to ca. 45° C.) After stirring for 3 hours in the ice bath the crystallizate which is formed is aspirated, the residue is washed three times with 500 ml water each time and dried in a drying cupboard at 40° C. The crude product--295.5 g light brown crystals--is purified chromatographically. The azo compound is dissolved in 1 l toluol/methylene chloride 2:5 and applied to a silica gel 60 (Merck) column with an inside diameter of 11.5 cm, filling height of 1.2 m and eluted with toluol/methylene chloride 2:5. Fractions of ca. 70 ml are taken. The fractions 57-173 are combined and concentrated by evaporation. One obtains 134.2 g brown crystals. These are dissolved in 480 ml toluol at 80° C., cooled to 65° C. and 800 ml isohexane are added while stirring vigorously. It is allowed to cool to 20° C. while stirring, placed overnight in a refrigerator, the crystals which form are aspirated and the filter cake is washed twice with 300 ml ice-cold toluol/isohexane 1:1.3 and subsequently with 300 ml isohexane. Afterwards it is dried in a drying cupboard at 40° C. over diphosphorus pentoxide until constancy of weight. One obtains 119.9 g (55.5% of the theoretical yield) azo compound, light brown crystals, Fp 102°-103° C. TLC, silica gel 60 (Merck), mobile solvent: toluol/methylene chloride 2:5, Rf =0.37. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium nitrite In sulfuric acid; hydrogen bromide; acetic acid | 2.a a) a) 3,4,5-Tribromonitrobenzene At 20° C., with stirring and cooling with ice, a solution of 2,6-dibromo-4-nitro-aniline (47.2 g) in acetic acid (1.6 liters) is slowly poured into a solution of sodium nitrite (12 g) in concentrated sulphuric acid (85 ml). Then, the mixture is stirred for 20 minutes at ambient temperature. The solution thus prepared is then slowly added with stirring and cooling with ice to a solution of copper (I) bromide (12.8 g) in 63% hydrobromic acid (40 ml). After it has all been added the mixture is stirred for a further 30 minutes. It is diluted with water, the precipitate is filtered off and washed with water. This crude product is recrystallized from methanol. Colorless crystals, m.p. 110° C. | |
With sodium nitrite In sulfuric acid; hydrogen bromide; acetic acid | 2.a (a) (a) 3,4,5-Tribromonitrobenzene At 20° C., with stirring and cooling with ice, a solution of 2,6-dibromo-4-nitro-aniline (47.2 g) in acetic acid (1.6 liters) is slowly poured into a solution of sodium nitrite (12 g) in concentrated sulphuric acid (85 ml). Then, the mixture is stirred for 20 minutes at ambient temperature. The solution thus prepared is then slowly added with stirring and cooling with ice to a solution of copper (I) bromide (12.8 g) in 63% hydrobromic acid (40 ml)/. After it has all been added the mixture is stirred for a further 30 minutes. It is diluted with water, the precipitate is filtered off and washed with water. This crude product is recrystallized from methanol. Colorless crystals, m.p. 110° C. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2,6-dibromo-4-nitroaniline With nitrosylsulfuric acid In water at 15 - 20℃; for 2h; Stage #2: 3-acetylamino-N-(3-phthalimidopropyl)-N-ethylaniline In water; acetic acid at 0 - 20℃; | I.1.B,C 21 g of 40 % nitrosylsulfuric acid are placed in a laboratory reaction apparatus. At 15 - 20°C, 6.1 g of 2,6-dibromo-4-nitroaniline are introduced. After being stirred for 2 hours at 15 - 200C, the mixture is poured into 60 g of ice-water and stirred for a further 15 min. The excess nitrite is destroyed by addition of sulfamic acid.C. Coupling7.4 g of 4-acetylamino-N-(3-phthalimidopropyl)-N-ethylaniline in 50 ml of 80 % acetic acid are placed in a laboratory reaction apparatus and 3 drops of Surfynol 104 E (2,4,7,9-tetramethyl- 5-decyne-4,7-diol) are added thereto. After addition of 40 g of ice, the solution of the diazonium salt prepared under B is slowly added dropwise so that the internal temperature is 0 - 5°C. The mixture is stirred for 1 hour at 0 - 5°C and overnight at RT. After addition of 100 ml of water, the solid is filtered off with suction, washed with deionised water and dried. 13.1 g of the compound of formula (101a) are obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 84% 2: 13% | With dihydrogen peroxide; potassium bromide In water; acetonitrile | |
With N-Bromosuccinimide In water at 20℃; for 8h; | ||
1: 98 %Chromat. 2: 2 %Chromat. | With sodium persulfate; copper(ll) sulfate pentahydrate; sodium bromide In water; acetonitrile at 7 - 25℃; for 24h; Overall yield = 98 percent; Overall yield = 1.5 g; regioselective reaction; | 4-Bromo-2-nitroaniline (2a); Typical Procedure for Bromination General procedure: 2-Nitroaniline (1.0 g, 7.24 mmol) was added to a suspension of CuSO4·5H2O (0.452 g, 1.81 mmol, 25 mol%) in a mixture of CH3CN (20mL) and H2O (10 mL) at 25 °C, and the mixture was stirred at 25 °C for15 min. NaBr (1.34 g, 13.0 mmol, 1.8 equiv.) and Na2S2O8 (2.41 g, 10.1mmol, 1.4 equiv.) were then added simultaneously in three portionsat 7 °C over 15 min. After addition was complete, the mixture was furtherstirred at 7 °C for 2 h and at 25 °C for 22 h. Na2S2O3 (572 mg, 3.62 mmol) was added to the mixture. The pH value of the mixture wasthen adjusted to 9.0 by adding 10% aq. NaOH (8 mL). The mixture wasdiluted with H2O (100 mL) and extracted with AcOEt (100 mL). Theorganic phase was separated and subjected to HPLC analysis (X BridgeC18, 5 m, 4.6 × 150 mm, 30 °C, 1 mL min-1, 50-90% CH3CN (0-20min) then 50% (20-40 min), 254 nm) to obtain the assay yield of 2a(1.49 g, 94.9%) and the ratio of 2a/3a (99.9:0.1). Pure samples of 2aand 3a for analysis were obtained by purification of the evaporatedmixture with silica gel column chromatography (n-hexane/AcOEt =15:1). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 2,6-dibromo-4-nitroaniline With potassium hydride In tetrahydrofuran at 0℃; for 0.25h; Inert atmosphere; Stage #2: 1,1'-carbonyldiimidazole In tetrahydrofuran; 1,4-dioxane at 0 - 20℃; Inert atmosphere; Stage #3: (1R,2R)-N,N-dimethylcyclohexane-1,2-diamine In tetrahydrofuran; 1,4-dioxane at 20℃; for 20h; Inert atmosphere; | 4.2. General procedure for the preparation of ureas from sulfinamides, sulfonamides or anilines (Eq. 1) General procedure: A suspension of potassium hydride (3 equiv) in THF (0.6 M) was cooled in an ice-water bath. A solution of sulfonamide, sulfonamide or aniline (1.0 equiv) in THF (0.20 M) was added dropwise, and the suspension was stirred for 15 min. 1,1'-Carbonyldiimidazole (1.0 equiv) was dissolved in 1:1 THF/dioxane (0.20 M) and added dropwise to the reaction mixture, resulting in the formation of a white precipitate. The ice-water bath was removed, and the reaction mixture was allowed to warm to ambient temperature and was stirred for 2 h. A solution of diamine S-1 (1.0 equiv) in THF (1.0 M) was added dropwise, and the suspension was stirred at room temperature for 20 h. The reaction was quenched with a solution of acetic acid (3 equiv) in THF (1.0 M). The crude product was concentrated in vacuo and purified by silica gel chromatography. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium phosphate tribasic heptahydrate; palladium diacetate In water; N,N-dimethyl-formamide at 80℃; for 0.25h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
99% | With potassium phosphate tribasic heptahydrate; palladium diacetate In water; N,N-dimethyl-formamide at 80℃; for 0.333333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With potassium phosphate tribasic heptahydrate; palladium diacetate In water; N,N-dimethyl-formamide at 80℃; for 0.416667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
98% | With potassium phosphate tribasic heptahydrate; palladium diacetate In water; N,N-dimethyl-formamide at 80℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | With potassium phosphate tribasic heptahydrate; palladium diacetate In water; N,N-dimethyl-formamide at 80℃; for 0.333333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide In N,N-dimethyl-formamide at 20℃; for 5h; | ||
8.08 g | With sodium hydroxide In N,N-dimethyl-formamide at 20℃; for 5h; | 10 The preparation of compound B-115 3.12g (0.078 mol) of sodium hydroxide was added to a solution of 8.07g(0.039 mol) of 2,6-dichloro-4-nitroanilinein 60 mL of DMF, followed by addition of 7.80g (0.039 mol) of 2,4,5,6-tetrafluoroisophthalonitrile under stirring, the mixturewas stirred for 5 h after addition at room temperature. After the reaction was over by Thin-Layer Chromatographymonitoring, the reaction mixture was poured into water and extracted with ethyl acetate, the organic phase was washedwith water and saturated brine, dried over anhydrous magnesium sulfate, filtered and then concentrated under reducedpressure. The residue was purified through silica column (ethyl acetate/petroleum ether (boiling point range 60-90°C)= 1:5, as an eluent) to give 8.08 g of compound B-115 as yellowish solid, m.p. 164-166°C.[0096] 1H-NMR (300MHz, internal standard TMS, solvent CDCl3) δ(ppm): 6.88(br, 1H, NH), 8.53(s, 2H, Ph-3,5-2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With tetrabutylammomium bromide; palladium diacetate; sodium carbonate In water at 150℃; for 0.5h; Inert atmosphere; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2,6-dibromo-4-nitroaniline; naphthalene-1,5-disulfonate In ethyl acetate at 50℃; for 0.166667h; Stage #2: With tert.-butylnitrite In ethyl acetate at 25℃; for 0.333333h; | 2.2 Typical synthesis of stable solid diazonium salt of 2,4-dinitroaniline 2,4-Dinitroaniline (10mmol) and 1,5-naphthalenedisulfonic acid (10mmol) were dissolved in 100mL ethyl acetate at 50°C and the mixture was stirred for 10min. Tert-butyl nitrite (15mmol) was added by dropping to the mixture for about 2minat 25°C. The reaction solution was further stirred for 20min with the temperature maintained at 25°C. A salmon pink solid was obtained by suction filtration and air drying. The yield was 99.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2,6-dibromo-4-nitroaniline With naphthalene-1,5-disulfonate In ethyl acetate at 50℃; for 0.166667h; Stage #2: With tert.-butylnitrite In ethyl acetate at 25℃; for 0.333333h; Stage #3: N-ethyl-N-(2-cyanoethyl)aniline With hydrogenchloride In water at 0 - 5℃; for 0.2h; | 2.4 Typical procedure for coupling General procedure: N,N-Diethylaniline (10mmol) was dissolved in 80mL water with 1.2mL 37% hydrochloric acid and then the salmon pink diazonium salt of 2,4-dinitroaniline was quickly added within 2minat 0°C-5°C followed by adjusting the pH to 4-5 with 2M NaOH solution. The reaction endpoint was confirmed by color reaction using H-acid. The precipitated dye was filtered, washed with water and dried at 80°C to afford the crude product. The crude yield was 95.0% and the degree of purity was 97.0%. | |
Stage #1: 2,6-dibromo-4-nitroaniline With nitrosylsulfuric acid; sulfuric acid at 5 - 40℃; for 5h; Stage #2: N-ethyl-N-(2-cyanoethyl)aniline With urea at 10 - 80℃; for 5.25h; | Preparation 16 A) adding sulfuric acid to the diazo kettle,Open the diazo kettle stir,And then slowly add nitrosyl sulfuric acid,Control the temperature does not exceed 40 ,Plus finished, cooling to 25 ,The intermediate 2,6-dibromo-4-nitroaniline was added slowly,Plus 5 ~ 30 in the incubation reaction 5 hours,To obtain a diazo component, stand-by;B) adding water to the diazo dilution kettle,Ice, cool to below 5 ,Pressed into the above-mentioned diazonium solution for dilution,Control the dilution temperature below 5 ,Pressure, add activated carbon,Stir for 60 minutes, filter,The diazo filtrate into the coupling kettle.C) Diazo filtrate is completed,Open the coupling kettle stir,Ice was added urea and peregal,Stir for 15 minutes,Adding isooctanol,Control the temperature below 10 ,The addition of the coupling component N-ethyl-N-cyanoethylaniline,Dropping time 3 hours, plus finished,Control temperature 10 ~ 15 incubation reaction 2 hours,Slowly warming to 80 turn crystal,Filtered and washed with water to give the product (III-1). | |
1600 kg | Stage #1: 2,6-dibromo-4-nitroaniline With nitrosylsulfuric acid; sulfuric acid at 15 - 25℃; for 5h; Industrial scale; Stage #2: N-ethyl-N-(2-cyanoethyl)aniline With aminosulfonic acid at -3 - 60℃; for 5h; Industrial scale; | 1 Example 1: 98% 500kg sulfuric acid, 40% 1094kg nitrosylsulfuric acid were added to the reaction vessel, cold saline spaced jacket temperature was controlled at 15-25 °C. 93% of 2,6-dibromo-4-nitro aniline 1075.3kg was slowly added. After the addition was complete, the reaction was kept for 5h, to be coupled with the diazonium salt. In the coupling kettle, 5 kg of sulfamic acid, OP-105kg of additive, 587kg (N-ethyl-N-cyanoethylaniline) of 98% coupling component, 7000kg of crushed ice. The diazonium salt was added dropwise under stirring, and the addition time was 2 h. After the completion of the dropwise addition, the ice was kept at a temperature of -3 °C for 2 hours, and then heated to 60 °C with steam for 1 h. The material is pumped into the filter press, washed at 50 °C hot water, and the filter cake is dried 1600 kg, HPLC is 98%. |
Stage #1: 2,6-dibromo-4-nitroaniline With nitrosylsulfuric acid; sulfuric acid at 20 - 40℃; for 6h; Stage #2: N-ethyl-N-(2-cyanoethyl)aniline With urea at 10 - 80℃; for 5h; | 14 Preparation Example 14 a) Add sulfuric acid to the diazo kettle, start stirring,Then slowly add nitrosyl sulfuric acid to control the temperature not to exceed 40 ° C. After the addition, cool down to 20 ° CSlowly and evenly add the intermediate 2,6-dibromo-4-nitroaniline,After the addition, the reaction was incubated at 25-30 ° C for 6 hours, and was set aside.b) Add water and ice to the diazo dilution kettle,Reduce the temperature to below 5 ° C, press in the diazo solution to be used for dilution, control the dilution temperature to not exceed 5 ° C, press down, add diatomite, stir for 30 minutes, and filter.The filtrate was poured into a coupling kettle.c) After the filtration is completed, open the coupling kettle and stir, add ice, urea, and evenly add, stir for 15 minutes.Add isooctanol and control the temperature below 10 ,Adding the coupling component N-ethyl-cyanoethylaniline dropwise,The addition time is about 3 hours.Control the temperature at 10 ~ 15 for 2 hours.The temperature was gradually raised to 50 to 80 ° C, and the crystals were transformed, filtered, and washed with water to obtain product (II-2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
90.45% | Stage #1: 2,6-dibromo-4-nitroaniline With tert.-butylnitrite; naphthalene-1,5-disulfonate In 1,2-dimethoxyethane at 20℃; for 1h; Stage #2: m-acetylamino-N,N-diethylanilne With sodium carbonate; naphthalene-1,5-disulfonate In water at 0℃; for 0.166667h; | 4 Preparation of N,N-diethyl-4-(2,6-dibromo-4-nitrophenylazo)-3-acetamidoaniline dye Diazotization reaction: 2.96 g of 2,6-dibromo-4-nitroaniline was dissolved in 60 mL of ethylene glycol dimethyl ether, To a solution of 2,6-dibromo-4-nitroaniline was added 4.32 g of 1,5-naphthalenedisulfonic acid, 1.72 g of t-butyl nitrite was added with stirring at 20 °C, reacted at 20 ° C for 1 h, Get diazonium salt; Coupling reaction: 2.06 g of N,N-diethyl-3-acetamidoaniline was dissolved in 2.88 g of 1,5-naphthalenedisulfonic acid 100 mL of water was added at 0 °C to a diazonium salt obtained by the diazotization reaction step, With anhydrous sodium carbonate to adjust the pH to 4~6, 0 °C reaction 10min, adjust the pH to neutral, filter, wash,Dried to give N,N-diethyl-4-(2,6-dibromo-4-nitrophenylazo)-3-acetylaminoaniline dye in a yield of 90.45%. |
Stage #1: 2,6-dibromo-4-nitroaniline With naphthalene-1,5-disulfonate In ethyl acetate at 50℃; for 0.166667h; Stage #2: With tert.-butylnitrite In ethyl acetate at 25℃; for 0.333333h; Stage #3: m-acetylamino-N,N-diethylanilne With hydrogenchloride In water at 0 - 5℃; for 0.1h; | 2.4 Typical procedure for coupling General procedure: N,N-Diethylaniline (10mmol) was dissolved in 80mL water with 1.2mL 37% hydrochloric acid and then the salmon pink diazonium salt of 2,4-dinitroaniline was quickly added within 2minat 0°C-5°C followed by adjusting the pH to 4-5 with 2M NaOH solution. The reaction endpoint was confirmed by color reaction using H-acid. The precipitated dye was filtered, washed with water and dried at 80°C to afford the crude product. The crude yield was 95.0% and the degree of purity was 97.0%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: 2,6-dibromo-4-nitroaniline With sulfuric acid at 25 - 35℃; for 2h; Stage #2: With nitrosylsulfuric acid at 20 - 28℃; Stage #3: N,N-bis(2-cyanoethyl)aniline; N-methyl-N-phenyl-benzenemethanamine With sulfuric acid; aminosulfonic acid In water at 0 - 70℃; for 5h; Overall yield = 94.4 %; | 2 Example 2 14.8 g of 2,6-dibromo-4-nitroaniline was added to 12 g of 98% sulfuric acid at 25 to 35 ° C and stirred2 hours.Maintaining at 20 ~ 28 slowly dropping 16.4 g of 40% nitrosyl sulfuric acid solution, and then continue to protectHolding at this temperature for 2 to 4 hours to complete the diazotization reaction.2 g of N, N -dicyanoethylaniline, 8.2Methyl-N-benzylaniline, 90 mL of water, 10 mL of sulfuric acid and 0.2 mL of sulfamic acid to prepare a mixed solutionLiquid, and the prepared diazo solution in the 0-8 ° C coupling reaction, the reaction temperature increased to 3 hours after the65-70 ° C for 2 hours, filtration, washing the product to eluate pH value of 6-7, in compound 3 and4, the yield of the mixed filter cake was 94.4%. The total content of the combined product was 94.3% by HPLC analysis. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | With tetrafluoroboric acid; acetic acid; isopentyl nitrite In water at 20℃; for 0.0833333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With nitrosylsulfuric acid; sulfuric acid In ethyl acetate at 0 - 5℃; for 0.45h; | 2.2.1. Preparation of the stable aryl diazonium sulfate 2,6-dibromo-4-nitrobenzenamine (10 mmol) was dissolved in 150 mlethyl acetate in 50 °C water bath, and then this mixture was cooled to 0 °C. A cold solution of NOHSO4 (11 mmol, 40 wt % in H2SO4) wasadded over 2 min under stirring with the temperature was maintained at0-5° C. The formation of a solid kelly diazonium salt was observed. Thereaction system was stirred for another 25 min and the completion of thereaction was monitored using thin-layer chromatography (TLC). Thenthe solid diazonium salt was gained by filtration. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | Stage #1: 2-oxo-2H-chromene-3-carboxylic acid With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 0.5h; Stage #2: 2,6-dibromo-4-nitroaniline With triethylamine In dichloromethane at 20℃; for 12h; | 4.1.3. Synthesis of 2-Oxo-N-substituted phenyl-2H-chromene-3-carboxamide (13a-13r) General procedure: To the coumarin-3-carboxylic acid (1.0 g) in 20 ml dry DCM was added EDCl-HCl (0.6 g), and HOBt (0.55 g). After stirring at RT for 30 min, the amine (1.1 equiv) was added followed by triethylamine (1 ml). The reaction mixture was stirred at RT for 12 h. The progress of the reaction was monitored by using TLC (ethyl acetate/n-hexane: 30:70). After completion of the reaction, the reaction mixture was diluted with DCM and washed with 1M HCl solution. The organic layer was separated and further treated with saturated sodium bicarbonate solution followed by brine solution. The organic layer was dried on sodium sulfate and concentrated by using rota-evaporator. The crude product was recrystallized in Dichloromethane: Pentane (2:8). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 88% 2: 2% | With indium; acetic acid In toluene at 80℃; for 6h; Inert atmosphere; | 2. General procedure for the indium-mediated reductive reaction of 2,6-disubstutited nitroanilines with 2,5-hexanedione or 1-phenyl-1,4-pentanedione to obtain 4-(1H-pyrrol-1-yl)aniline derivatives General procedure: To a mixture of the 2,6-dihalo-4-nitroaniline derivative (1.0 mmol) and indium powder (459 mg, 4.0 mmol) in toluene (2.5 mL) was added acetic acid (573 μL, 10 mmol) followed by the 1,4-diketone (2.0 mmol) in toluene (2.5 mL). The resulting mixture was stirred at 80 qC (2,5-hexanedione) or reflux (1-phenyl-1,4-pentanedione) under a nitrogen atmosphere. After the reaction was complete, the reaction mixture was diluted with EtOAc (30 mL) or CH 2 Cl 2 (30 mL) and filtered through a celite pad. The filtrate was poured onto a 10% aqueous solution of NaHCO 3 (30 mL), the layers separated, and the aqueous layer extracted with EtOAc (30 mL u 3) or CH2Cl2 (30 mL u 3). The combined organic layers were dried over MgSO 4 , filtered, and concentrated in vacuo. The resulting residue was purified using flash column chromatography on neutral silica gel eluted with EtOAc/hexane (v/v = 5/95) to give the corresponding pyrrole product. The structures of the pyrrole products, which were mostly novel compounds, were characterized using 1 H NMR, 13 C NMR and FTIR spectroscopy, GC-MS, and HRMS. 2,6-Dibromo-4-(2,5-dimethyl-1H-pyrrol-1-yl)aniline (1). Yield 88%. White solid, mp 112-113 o C. TLC (30% EtOAc/hexane) R f 0.68; 1 H NMR (400 MHz, CDCl 3 ) δ 7.27 (s, 2H), 5.84 (s, 2H), 4.67 (s, 2H), 2.02 (s, 6H); 13 C NMR (100 MHz, CDCl 3 ) δ 141.6, 131.5, 129.8, 107.8, 105.6, 12.9; IR 3464, 3356, 3059, 2974, 1612, 1574, 1481, 1408, 1273 cm -1 ; GC-MS m/z (rel intensity) 342 (M + , 100), 327 (7), 261 (7), 247 (14), 171(20), 154 (12), 123 (8); HRMS m/z calc. for C 12 H 12 N 2 Br 2 341.9367, found 341. 9391. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
63% | With indium; acetic acid In toluene for 8h; Inert atmosphere; Reflux; | 2. General procedure for the indium-mediated reductive reaction of 2,6-disubstutited nitroanilines with 2,5-hexanedione or 1-phenyl-1,4-pentanedione to obtain 4-(1H-pyrrol-1-yl)aniline derivatives General procedure: To a mixture of the 2,6-dihalo-4-nitroaniline derivative (1.0 mmol) and indium powder (459 mg, 4.0 mmol) in toluene (2.5 mL) was added acetic acid (573 μL, 10 mmol) followed by the 1,4-diketone (2.0 mmol) in toluene (2.5 mL). The resulting mixture was stirred at 80 qC (2,5-hexanedione) or reflux (1-phenyl-1,4-pentanedione) under a nitrogen atmosphere. After the reaction was complete, the reaction mixture was diluted with EtOAc (30 mL) or CH 2 Cl 2 (30 mL) and filtered through a celite pad. The filtrate was poured onto a 10% aqueous solution of NaHCO 3 (30 mL), the layers separated, and the aqueous layer extracted with EtOAc (30 mL u 3) or CH2Cl2 (30 mL u 3). The combined organic layers were dried over MgSO 4 , filtered, and concentrated in vacuo. The resulting residue was purified using flash column chromatography on neutral silica gel eluted with EtOAc/hexane (v/v = 5/95) to give the corresponding pyrrole product. The structures of the pyrrole products, which were mostly novel compounds, were characterized using 1 H NMR, 13 C NMR and FTIR spectroscopy, GC-MS, and HRMS. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
83.4% | Stage #1: 2,6-dibromo-4-nitroaniline With sulfuric acid; nitrosyl sulphuric acid at 20℃; Cooling with ice; Stage #2: 3-methyl-N-ethyl-N-(2-benzoyloxyethyl)aniline at 0 - 5℃; for 3h; | 1.2 Weigh 6g of concentrated sulfuric acid in a dry 100ml three-necked flask, cool the temperature in a water bath to below 20°C, add 8.7g of nitrosyl sulfuric acid, stir well and then cool down to about 20°C in an ice-water bath, and then slowly add 7.4g to a temperature around 20°C. 2,6-Dibromo-p-nitroaniline, add about 1h, after the addition, control the temperature at 20 and keep it for 3-4h to obtain a transparent diazonium liquid; then, add dropwise within 1h to the product obtained in step A for coupling reaction , Add ice to control the reaction temperature 0-5, and keep it at 0-5 for 2h to complete the coupling reaction, then naturally stir to room temperature, then filter, wash with water, and dry again, the yield of disperse brown is about 83.4%, which is detected by HPLC The purity is 96.3%. |
Tags: 827-94-1 synthesis path| 827-94-1 SDS| 827-94-1 COA| 827-94-1 purity| 827-94-1 application| 827-94-1 NMR| 827-94-1 COA| 827-94-1 structure
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P332 + P313 | IF SKIN irritation occurs: Get medical advice/attention. |
P333 + P313 | IF SKIN irritation or rash occurs: Get medical advice/attention. |
P335 + P334 | Brush off loose particles from skin. Immerse in cool water/wrap in wet bandages. |
P337 + P313 | IF eye irritation persists: Get medical advice/attention. |
P342 + P311 | IF experiencing respiratory symptoms: call a POISON CENTER or doctor/physician. |
P370 + P376 | In case of fire: Stop leak if safe to Do so. |
P370 + P378 | In case of fire: |
P370 + P380 | In case of fire: Evacuate area. |
P370 + P380 + P375 | In case of fire: Evacuate area. Fight fire remotely due to the risk of explosion. |
P371 + P380 + P375 | In case of major fire and large quantities: Evacuate area. Fight fire remotely due to the risk of explosion. |
Storage | |
Code | Phrase |
P401 | |
P402 | Store in a dry place. |
P403 | Store in a well-ventilated place. |
P404 | Store in a closed container. |
P405 | Store locked up. |
P406 | Store in corrosive resistant/ container with a resistant inner liner. |
P407 | Maintain air gap between stacks/pallets. |
P410 | Protect from sunlight. |
P411 | |
P412 | Do not expose to temperatures exceeding 50 oC/ 122 oF. |
P413 | |
P420 | Store away from other materials. |
P422 | |
P402 + P404 | Store in a dry place. Store in a closed container. |
P403 + P233 | Store in a well-ventilated place. Keep container tightly closed. |
P403 + P235 | Store in a well-ventilated place. Keep cool. |
P410 + P403 | Protect from sunlight. Store in a well-ventilated place. |
P410 + P412 | Protect from sunlight. Do not expose to temperatures exceeding 50 oC/122oF. |
P411 + P235 | Keep cool. |
Disposal | |
Code | Phrase |
P501 | Dispose of contents/container to ... |
P502 | Refer to manufacturer/supplier for information on recovery/recycling |
Physical hazards | |
Code | Phrase |
H200 | Unstable explosive |
H201 | Explosive; mass explosion hazard |
H202 | Explosive; severe projection hazard |
H203 | Explosive; fire, blast or projection hazard |
H204 | Fire or projection hazard |
H205 | May mass explode in fire |
H220 | Extremely flammable gas |
H221 | Flammable gas |
H222 | Extremely flammable aerosol |
H223 | Flammable aerosol |
H224 | Extremely flammable liquid and vapour |
H225 | Highly flammable liquid and vapour |
H226 | Flammable liquid and vapour |
H227 | Combustible liquid |
H228 | Flammable solid |
H229 | Pressurized container: may burst if heated |
H230 | May react explosively even in the absence of air |
H231 | May react explosively even in the absence of air at elevated pressure and/or temperature |
H240 | Heating may cause an explosion |
H241 | Heating may cause a fire or explosion |
H242 | Heating may cause a fire |
H250 | Catches fire spontaneously if exposed to air |
H251 | Self-heating; may catch fire |
H252 | Self-heating in large quantities; may catch fire |
H260 | In contact with water releases flammable gases which may ignite spontaneously |
H261 | In contact with water releases flammable gas |
H270 | May cause or intensify fire; oxidizer |
H271 | May cause fire or explosion; strong oxidizer |
H272 | May intensify fire; oxidizer |
H280 | Contains gas under pressure; may explode if heated |
H281 | Contains refrigerated gas; may cause cryogenic burns or injury |
H290 | May be corrosive to metals |
Health hazards | |
Code | Phrase |
H300 | Fatal if swallowed |
H301 | Toxic if swallowed |
H302 | Harmful if swallowed |
H303 | May be harmful if swallowed |
H304 | May be fatal if swallowed and enters airways |
H305 | May be harmful if swallowed and enters airways |
H310 | Fatal in contact with skin |
H311 | Toxic in contact with skin |
H312 | Harmful in contact with skin |
H313 | May be harmful in contact with skin |
H314 | Causes severe skin burns and eye damage |
H315 | Causes skin irritation |
H316 | Causes mild skin irritation |
H317 | May cause an allergic skin reaction |
H318 | Causes serious eye damage |
H319 | Causes serious eye irritation |
H320 | Causes eye irritation |
H330 | Fatal if inhaled |
H331 | Toxic if inhaled |
H332 | Harmful if inhaled |
H333 | May be harmful if inhaled |
H334 | May cause allergy or asthma symptoms or breathing difficulties if inhaled |
H335 | May cause respiratory irritation |
H336 | May cause drowsiness or dizziness |
H340 | May cause genetic defects |
H341 | Suspected of causing genetic defects |
H350 | May cause cancer |
H351 | Suspected of causing cancer |
H360 | May damage fertility or the unborn child |
H361 | Suspected of damaging fertility or the unborn child |
H361d | Suspected of damaging the unborn child |
H362 | May cause harm to breast-fed children |
H370 | Causes damage to organs |
H371 | May cause damage to organs |
H372 | Causes damage to organs through prolonged or repeated exposure |
H373 | May cause damage to organs through prolonged or repeated exposure |
Environmental hazards | |
Code | Phrase |
H400 | Very toxic to aquatic life |
H401 | Toxic to aquatic life |
H402 | Harmful to aquatic life |
H410 | Very toxic to aquatic life with long-lasting effects |
H411 | Toxic to aquatic life with long-lasting effects |
H412 | Harmful to aquatic life with long-lasting effects |
H413 | May cause long-lasting harmful effects to aquatic life |
H420 | Harms public health and the environment by destroying ozone in the upper atmosphere |
Sorry,this product has been discontinued.
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