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CAS No. : | 20265-96-7 | MDL No. : | MFCD00042057 |
Formula : | C6H7Cl2N | Boiling Point : | - |
Linear Structure Formula : | - | InChI Key : | ISJBQSJDQZLCSF-UHFFFAOYSA-N |
M.W : | 164.03 | Pubchem ID : | 5284363 |
Synonyms : |
|
Signal Word: | Danger | Class: | 6.1 |
Precautionary Statements: | P260-P262-P264-P270-P271-P280-P284-P301+P310+P330-P302+P352+P310+P361+P364-P304+P340+P310-P403+P233-P405-P501 | UN#: | 2811 |
Hazard Statements: | H300+H310+H330-H350-H360 | Packing Group: | Ⅲ |
GHS Pictogram: |
* 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 |
---|---|---|
With water |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
67% | In acetic acid for 3h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
50% | With phosphorus pentoxide; N,N-dimethylcyclohexylamine hydrochloride In water at 180℃; for 0.583333h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | In chlorobenzene at 140 - 150℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | In chlorobenzene at 140 - 150℃; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | Stage #1: p-chloroaniline hydrochloride With hydrogenchloride; sodium nitrite at 0℃; Stage #2: azulene With sodium acetate In ethanol at 20℃; for 0.166667h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
66% | With hydrogenchloride; sodium acetate; sodium nitrite In ethanol; water at 0 - 5℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
45% | Stage #1: p-chloroaniline hydrochloride With hydrogenchloride; ethyl nitrite In ethanol at -5 - 0℃; Stage #2: sodium acetylacetonate In ethanol for 0.5h; Heating; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium nitrite In water | ||
With hydrogenchloride; sodium nitrite | ||
With sodium nitrite In hydrogenchloride; water Cooling; liquid HCl; |
With sodium nitrite In water | ||
With sodium nitrite In water | General procedure: A cold solution of aryldiazonium salt (2.0 mmol) was prepared by adding a solution of NaNO2 (2.2 mmol, 0.15 g into 1.0 mL H2O) to a cold solution of arylamine hydrochloride (2.0 mmol of arylamine in 1.5 mL conc. HCl). The resulting solution of aryldiazonium salt was added drop wise to a mixture of 8-methyl-4-hydroxyquinoline-2-(1H)-one (II) (0.35 g, 2.0 mmol) in 10 mL aqueous NaOH (20 mmol, 0.8 g) at 0-5 °C. The pH of the reaction mixture was maintained at 9-10 by adding 2.5% sodium hydroxide solution. The resulting mixture was continually stirred at 0-5 °C for 2 h. After completion of the reaction the pH was regulated to 4-5 by simultaneous additions of 10% hydrochloric acid solution. The resulting solid was then filtered off, washed with cold ethanol, dried at 50 °C in an oven and then recrystallized from DMF. The purity of all compounds was evaluated by thin layer chromatography. The physical and spectral data of the purified dyes are available in the supplementary data accompanied with this paper. | |
With tert.-butylnitrite In acetonitrile at 20℃; for 0.166667h; | ||
With sodium nitrite Cooling; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | Stage #1: p-chloroaniline hydrochloride With sodium nitrite In water Stage #2: ethyl (E)-3-(dimethylamino)acrylate With sodium acetate In ethanol; water at 20℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: p-chloroaniline hydrochloride With sodium nitrite In water Stage #2: (E)-3-(dimethylamino)acrolein With sodium acetate In ethanol; water at 20℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: p-chloroaniline hydrochloride With sodium nitrite In water Stage #2: 2-[(4-chlorophenyl)hydrazono]-3-oxopropionic acid ethyl ester With sodium acetate In ethanol; water at 20℃; for 0.5h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | In water at 20℃; for 24h; | |
75% | In water at 20℃; for 4h; | A.a A - Method of general obtainment of type I 1 ,2 , 3-triazole derivatives :dia Tipo I(Translation: diazomalonaldehyde)In a balloon containing 5 mmol of diazomalonaldehyde 30,0 mL of distilled water was added. Then, a recently prepared solution with 4,5 mmol of the chloride derivative of the desired amine was added slowly into 5 mL of distilled water. The reaction mixture was under disturbance at room temperature, for 4 hours, and the precipitation of triazole product was observed. The solid was insulated by filtration and washed with ice water.This methodology was used to obtain the below mentioned compounds: a - 4-carboxaldehyde-l- (4-chlorophenyl) -IH-I, 2, 3-triazole (114a) The derivate (114a) was prepared with 75,0% of output, as of the reaction of the diazomalonaldehyde with the 4- chloroaniline chloride, thus obtaining an amorphous white EPO solid with fusion point at 159,0 - 161,00C.=> 1H RMN (500,00MHz; CDCl3/Me4Si; δ (ppm) ) : 7,56 (d, 2H, H3X and E5 J=I, 5 and 3,0Hz); 7,74(d, 2H, H2 " and H6 J=7,0Hz); 8,53 (s, IH, H5) ; 10,22 (s, IH, CHO) ; => 13C RMN (125,0 MHz, CDCl3/Me4Si; δ(ppm) ) : 122,0 (C3"and C5^) ; 123,0 (C5) ; 130,2 (C2vand C6^) ; 134,6 (CD; 135,8 (C4X) ; 148,2 (C4) ; 184,9 (CHO) ;=» IV (KBr) cm"1: 3094 (v C-Har) ; 2842 (v C-Haldehyde) ; 1705 (v C=O) ; => EM (m/z) : 207 (M+; 32%); 178 (M+-29; 100%); 151 (M+-56; 75%); 111 (M+- 96; 86%); 89(M+- 118; 35%); 75 (M+-132; 84%); => Elementary Analysis (theoretical / experimental) : C- 52,05% / 52,37%; H- 2,91% / 2,76%; N- 20,24% / 20,64%. b - 4-carboxaldehyde-l- (4-bromophenyl) -IH-I, 2, 3-triazole (114b)The derivative (114b) was prepared with 76,0% of output, as of the reaction of the diazomalonaldehyde with the 4-bromoaniline chloride, thus obtaining an amorphous white solid with fusion point at 190, 0-191, 00C. => RMN de 1H (500,00 MHz; CDCl3/Me4Si; δ (ppm)) : 7,68(d, 2H, H3S and H5 " r 8,54 (s, IH, H5); 10,22 (s, IH, CHO); => 13C RMN (125,0 MHz, CDCl3/Me4Si; δ(ppm)) : 122,2 (C2'and C6') ; 122,9 (C5) ; 123,7 (C4%) ; 133,2 (C3^and C5v) ; 135,1 (Cls) ; 148,2 (C4) ; 184,9 (CHO) ;=> IV (KBr) cm"1: 3098 (v C-Har) ; 2851 (v C-Haidehyde) ; 1698 (v C=O) ; EPO => EM (m/z) : 253 (M+; 11%); 224 (M+ - 29; 32%); 197 (M+ - 56; 18%); 157 (M+ - 96; 42%); 116 (M+ - 137; 100%); => Elementary Analysis (theoretical / experimental) :C- 42,88% / 42,77%; H- 2,40% / 2,36%;N- 16,67% / 16,90%. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
70% | Stage #1: p-chloroaniline hydrochloride With sodium nitrite In water cooling; Stage #2: 4-nitrophenyl-1-piperidinostyrene With sodium acetate In ethanol; water at 20℃; for 0.5h; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: p-chloroaniline hydrochloride With sodium nitrite In water cooling; Stage #2: 2-[2-(4-nitrophenyl)vinyl]malononitrile With sodium acetate In ethanol; water at 20℃; for 0.5h; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Multi-step reaction with 2 steps 1: 95 percent / aq. HCl / ethanol | ||
With hydrogenchloride In lithium hydroxide monohydrate | ||
Multi-step reaction with 2 steps 1: potassium carbonate / propan-2-one / 0 - 15 °C 2: thionyl chloride / methanol / 1.2 h / Reflux |
Multi-step reaction with 2 steps 1: potassium carbonate / propan-2-one / 11 h / 0 - 30 °C 2: thionyl chloride / methanol / 2.5 h / Reflux | ||
With hydrogenchloride In ethanol; lithium hydroxide monohydrate | ||
With hydrogenchloride at 0℃; | ||
With hydrogenchloride In lithium hydroxide monohydrate for 0.5h; Heating; | ||
Multi-step reaction with 2 steps 1: di-isopropyl ether 2: hydrogenchloride / lithium hydroxide monohydrate; ethanol / 40 °C | ||
Multi-step reaction with 2 steps 1: dichloromethane / 1 h / 20 °C / Inert atmosphere 2: hydrogenchloride / dichloromethane; lithium hydroxide monohydrate / 20 °C | ||
With hydrogenchloride In lithium hydroxide monohydrate at 60℃; for 0.166667h; | 1.1; 2.1; 3.1; 4.1; 5.1; 6.1 (1) Preparation of p-chlorobenzenediazonium chloride Weigh 4-chloroaniline (3.83g, 0.03mol), polyethylene glycol-600 (0.10g), measure 15mL (0.072mol) of 16% hydrochloric acid in a 150mL three-necked flask,Dissolve in a water bath at 60°C.Stir for 10 minutes, then put it in a cold water bath to precipitate 4-chloroaniline hydrochloride fine particles, add ice to keep the temperature below 10°C,Slowly add sodium nitrite solution (2.24g, 0.0324mol, add 8mL deionized water to dissolve).After stirring and reacting for 0.5h, a p-chlorobenzene diazonium chloride solution was obtained.Use starch-KI test paper to remove excess nitrous acid with urea. | |
With hydrogenchloride In diethyl ether at 0 - 20℃; for 3.3h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
In ethanol; for 2h;Heating / reflux;Product distribution / selectivity; | A mixture of 0.972 g (3.8 mmol) l-chloro-4-(4- pyridylmethyl)phthalazine, 0.656 g (4 mmol) 4-chloroaniline hydrochloride (Research Organics, Inc., Cleveland, Ohio, USA) and 20 ml ethanol is heated for 2 h under reflux. The reaction mixture is cooled in an ice bath, filtered, and the crystallizate washed with a little ethanol and ether. After drying under HV for 8 h at 110 C. and for 10 h at 150 C, the title compound is obtained as a result of thermal removal of HCl; m.p. >270 C; ' H NMR (DMSO-d 6 ) 9.80-11.40 (br), 8.89-8.94 (m, IH), 8.67 (d, 2H), 8.25-8.30 (m, IH), 8.06-8.17 (m, 2H), 7.87 (d, 2H), 7. 69 (d, 2H), 7.49 (d, 2H), 4.81 (s, 2H); ESI-MS: (M+H) +=347. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide In ethanol; water | 2 Example 2 STR50 (Process a) A mixture of 7.7 g (0.06 mol) of 4-chloroaniline hydrochloride, 7.4 g (0.05 mol) of 2-cyanoamino-4,6-dimethyl-pyrimidine and 150 ml of ethanol is heated at the boil under reflux for 15 hours. After cooling, the reaction mixture is diluted with 150 ml of water, and is rendered alkaline with 2N sodium hydroxide solution. The product which crystallizes out is filtered off under suction. 8.3 g (60% of theory) of N'-(4,6-dimethylpyrimidin-2-yl)-N"-(4-chlorophenyl)-guanidine of melting point 203° C. are obtained. | |
With sodium hydroxide In ethanol; water | 2 EXAMPLE 2 STR53 EXAMPLE 2 STR53 (Process a) A mixture of 7.7 g (0.06 mol) of 4-chloroaniline hydrochloride, 7.4 g (0.05 mol) of 2-cyanoamino-4,6-dimethyl-pyrimidine and 150 ml of ethanol is heated at the boil under reflux for 15 hours. After cooling, the reaction mixture is diluted with 150 ml of water, and is rendered alkaline with 2N sodium hydroxide solution. The product which crystallizes out is filtered off under suction. 8.3 g (60% of theory) of N'-(4,6-dimethylpyrimidin-2-yl)-N"-(4-chlorophenyl)-guanidine of melting point 203° C. are obtained. | |
With sodium hydroxide In ethanol; water | 2 (Process a) EXAMPLE 2 STR54 (Process a) A mixture of 7.7 g (0.06 mol) of 4-chloroaniline hydrochloride, 7.4 g (0.05 mol) of 2-cyanoamino-4,6-dimethyl-pyrimidine and 150 ml of ethanol is heated at the boil under reflux for 15 hours. After cooling, the reaction mixture is diluted with 150 ml of water, and is rendered alkaline with 2N sodium hydroxide solution. The product which crystallizes out is filtered off under suction. 8.3 g (60% of theory) of N'-(4,6-dimethylpyrimidin-2-yl)-N"-(4-chlorophenyl)-guanidine of melting point 203° C. are obtained. |
With sodium hydroxide In ethanol; water | (Process a) (Process a) A mixture of 7.7 g (0.06 mol) of 4-chloroaniline hydrochloride, 7.4 g (0.05 mol) of 2-cyanoamino-4,6-dimethyl-pyrimidine and 150 ml of ethanol is heated at the boil under reflux for 15 hours. After cooling, the reaction mixture is diluted with 150 ml of water, and is rendered alkalkine with 2N sodium hydroxide solution. The product which crystallizes out is filtered off under suction. 8.3 g (60% of theory) of N'-(4,6-dimethylpyrimidin-2-yl)-N"-(4-chlorophenyl)-guanidine of melting point 203° C. are obtained. | |
With sodium hydroxide In ethanol; water | 2 EXAMPLE 2 STR55 EXAMPLE 2 STR55 (Process a) A mixture of 7.7 g (0.06 mol) of 4-chloroaniline hydrochloride, 7.4 g (0.05 mol) of 2-cyanoamino-4,6-dimethyl-pyrimidine and 150 ml of ethanol is heated at the boil under reflux for 15 hours. After cooling, the reaction mixture is diluted with 150 ml of water, and is rendered alkaline with 2N sodium hydroxide solution. The product which crystallizes out is filtered off under suction. 8.3 g (60% of theory) of N'-(4,6-dimethylpyrimidin-2-yl)-N"-(4-chlorophenyl)-guanidine of melting point 203° C. are obtained. | |
With sodium hydroxide In ethanol; water | (Process a) (Process a) A mixture of 7.7 g (0.06 mol) of 4-chloroaniline hydrochloride, 7.4 g (0.05 mol) of 2-cyanoamino-4,6-dimethyl-pyrimidine and 150 ml of ethanol is heated at the boil under reflux for 15 hours. After cooling, the reaction mixture is diluted with 150 ml of water, and is rendered alkaline with 2N sodium hydroxide solution. The product which crystallizes out is filtered off under suction. 8.3 g (60% of theory) of N'-(4,6-dimethylpyrimidin-2-yl)-N"-(4-chlorophenyl)-guanidine of melting point 203° C. are obtained. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With sodium hydroxide In ethyl acetate; butan-1-ol | 14 EXAMPLE 14 EXAMPLE 14 p-Chloroaniline hydrochloride (1.25 g.) was dissolved in n-butanol (10 ml.) and heated to reflux. A cold solution of 2-exo-cyanamidobicyclo[2,2,1]hept-5-ene (1.07 g.) in butanol (10 ml.) was added slowly dropwise so that the mixture continued to reflux. One hour after the addition was complete the mixture was cooled, butanol evaporated off in vacuo and the residue dissolved in ethyl acetate (10 ml.). The organic phase was extracted with water (4 * 5 ml.). The combined aqueous phases were brought to pH7 with aqueous Na2 CO3 solution and extracted with ether. This removed unreacted p-chloroaniline. The residual aqueous phase was brought to pH 12 with aqueous 10N NaOH which precipitated pure product. It was filtered off, washed with water, dried and recrystallized from ethyl acetate to give 2-exo-[3-(p-chlorophenyl)guanidino]bicyclo[2,2,1]hept-5-ene, m.p. 206°-207°. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
46% | at 180℃; for 4h; | Preparation of Intermediate 1-(4-chloro-phenyl)-5-phenyl-pyrrolidin-2-one (1-1 a): EPO 1-1 aA mixture of 2.0 g (12.3 mmol) of 5-phenyl butyrolactone, 6.9 g (54 mmol) of 4- chloroaniline and 3.4 g (21 mmol) of 4-chloroaniline hydrochloride under nitrogen was heated at 18O0C (external temperature, sand bath) for 4 hours. The mixture was cooled to room temperature and poured into 50 ml of 1 M HCI, diluted with water and extracted with methylene chloride. The combined organic layers were dried (magnesium sulfate), filtered and evaporated. Purification by silica gel MPLC with chloroform gave 0.60 g (46%) of the title compound (1-1 a).1 H NMR (CDCI3): δ 2.0 (m, 1 H), 2.55-2.8 (m, 3H), 5.21 (dd, J = 7.5, 4.6, 1 H), 7.1-7.5 (m, 9H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
82% | Stage #1: p-chloroaniline hydrochloride With hydrogenchloride; sodium nitrile Stage #2: 3-Aminocrotononitrile With sodium acetate In ethanol at 20℃; for 1h; Stage #3: With hydrogenchloride; acetic acid for 0.25h; Heating; Further stages.; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
100% | Stage #1: 4-chlorobenzonitrile With 1% platinum on charcoal; ammonia; hydrogen; N-Cyanoguanidine In toluene at 90 - 100℃; for 6h; Autoclave; Large scale; Stage #2: With hydrogenchloride In water at 90 - 100℃; Large scale; | 1; 2; 3 Example 3 Preparation of p-chloroaniline hydrochloride Into a 2000L autoclave, 800L of toluene, 400kg of p-chloronitrobenzene, 1.2kg of 1% platinum-carbon wet product (0.4kg on dry basis, 66.7% of wet product moisture content), 40g of dicyandiamide, and 1.6kg of ammonia were sealed. The autoclave was evacuated for 10 minutes. Nitrogen was used to replace the air three times, and hydrogen was continuously substituted to replace the nitrogen three times. The pressure of the hydrogen gas was controlled to 1.0 MPa. The reaction solution was heated to 90-100 ° C and hydrogenated for 6 hours until the reaction solution ceased. Absorb hydrogen, reduce the temperature of the reaction solution to below 60 ° C, replace the hydrogen with nitrogen, filter off the catalyst by nitrogen pressure (to be applied), collect the filtrate into a 100L enamel reactor, add 4kg of activated carbon to decolorize, and add 424kg of concentrated hydrochloric acid to the filtrate. Warm to 90 ° C for 1 hour, continue to raise the temperature to 100 ° C, reflux through a water trap, toluene with water until no more water is separated, a large amount of white solids are suspended, cool the reaction solution to room temperature, and centrifuge to remove the mother liquor. A small amount of toluene was used to rinse the filter cake, and the filter cake was dried under reduced pressure at 80 ° C for 4 hours to obtain 400 kg of white crystal p-chloroaniline hydrochloride, with a weight yield of 100%, a molar yield of 96%, a purity of 99.94%, and a content of 99.89%. |
99% | Stage #1: 4-chlorobenzonitrile With iron(III) acetylacetonate; 1,1,3,3-Tetramethyldisiloxane In tetrahydrofuran at 60℃; for 48h; Inert atmosphere; Sealed tube; Stage #2: With hydrogenchloride In tetrahydrofuran; diethyl ether for 0.0833333h; | 4.1. General General procedure: In a solution of nitro compound (2 mmol) in 0.6 mL of THF were added Fe(acac)3 (10 mmol %, 70 mg) and TMDS (1.5 equiv or three Si-H, 0.53 mL). After 24 h (unless otherwise indicated) under heating the reaction mixture was diluted in a minimum of Et2O with a constant stirring. HCl (2 equiv) in Et2O was then added dropwise. A precipitate appears; the mixture was stirred for 5 min and filtered. It was washed several times with Et2O and dried to afford the desired product as a hydrochloride salt. |
97% | Stage #1: 4-chlorobenzonitrile With hydrogen; C19H12N4(2-)*C2H6OS*Co(2+) In ethanol at 120℃; for 15h; Autoclave; Stage #2: With hydrogenchloride In diethyl ether; dichloromethane |
95% | Stage #1: 4-chlorobenzonitrile With iron(III)-acetylacetonate; 1,1,3,3-Tetramethyldisiloxane; 1,2,3-trimethoxy glycerol ether at 80℃; for 24h; Inert atmosphere; Sealed tube; Green chemistry; Stage #2: With hydrogenchloride In diethyl ether at 20℃; for 0.0833333h; Green chemistry; | |
94% | Stage #1: 4-chlorobenzonitrile With potassium borohydride; TPGS-750-M In tetrahydrofuran; water at 20℃; for 11.5h; Inert atmosphere; Stage #2: With hydrogenchloride In tetrahydrofuran; water for 1h; | |
91% | Stage #1: 4-chlorobenzonitrile With iododioxobis(triphenylphosphine)rhenium(V); Dimethylphenylsilane In toluene for 1.5h; Reflux; Stage #2: With hydrogenchloride In diethyl ether; toluene | |
620 mg | Stage #1: 4-chlorobenzonitrile With phosgene; sodium tetrahydroborate; copper(II) sulfate In methanol at 20℃; Stage #2: With hydrogenchloride In methanol; diethyl ether | General Procedure for the Reduction of Aromatic Nitro Compounds General procedure: The catalyst precursor in form of a 0.04 M CuSO4 and 0.004 M CoCl2 solution (3.0 ml,3.0 mol% CuSO4, 0.3 mol% CoCl2) was added to a magnetically stirred solution ofthe nitro compound (4 mmol) in 25 ml methanol. The reaction was initiated by addingan initial portion of 210 mg (5.6 mmol) NaBH4, resulting in a color change to black(catalyst generated in situ) and vigorous gas evolution. Additional portions of NaBH4(7 × 35 mg, 7 × 0.9 mmol) NaBH4 were added in intervals of 3 min. Although thereaction was carried out at room temperature and under normal atmosphere, the generation of heat due to the exothermic character of the reaction usually heated the reaction mixture to 30-40C and cooling is generally not necessary on a small scale. However,for large scale reactions (10 mmol), a reflux condenser was attached. After 25 min,the reaction mixture was quenched by adding 30 ml of water and extracted with 3 ×40 ml of CH2Cl2. The combined organic layers were dried over MgSO4. After removal of the drying agent, 6 M HCl in ether (10 ml) was added to produce the more stable hydrochloride, which was freed from excess HCl, CH2Cl2 and Et2O under reduced pressure(10 mmHg). An aliquot of the amine was analyzed using GC-MS, 1H-NMR and 13C-NMR. The NMR data for the compounds are shown in Table 2. |
Multi-step reaction with 2 steps 1: [Fe{N(SiMe3)2}(4,5-bis(silylene)-2,7,9,9-tetramethyl-9H-acridin-10-ide)] / benzene-d6 / 12 h / 20 °C / Inert atmosphere 2: hydrogenchloride / water; diethyl ether |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
92% | Stage #1: p-chloroaniline hydrochloride With sodium nitrite In water Cooling; Stage #2: pyridine-2-acetonitrile With sodium acetate In ethanol; water at 20℃; Cooling; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | Stage #1: p-chloroaniline hydrochloride With sodium nitrite Cooling; Stage #2: (E)-3-(dimethylamino)-1-(naphthalen-1-yl)prop-2-en-1-one With sodium acetate at 20℃; for 0.5h; Cooling; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | With ethanol for 0.0166667h; Microwave irradiation; Neat (no solvent); |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: p-chloroaniline hydrochloride With water; sodium nitrite Cooling; Stage #2: C13H18N2O2 With sodium acetate In ethanol; water at 20℃; Cooling; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
88% | Stage #1: p-chloroaniline hydrochloride With water; sodium nitrite Cooling; Stage #2: C15H22N2O2 With sodium acetate In ethanol; water at 20℃; Cooling; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
91% | Stage #1: p-chloroaniline hydrochloride With water; sodium nitrite Cooling; Stage #2: C15H20N2O2 With sodium acetate In ethanol; water at 20℃; Cooling; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
79% | Stage #1: p-chloroaniline hydrochloride With water; sodium nitrite Cooling; Stage #2: C16H16N2O2 With sodium acetate In ethanol; water at 20℃; Cooling; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
93.1% | With thionyl chloride In methanol for 2.5h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97.9% | With thionyl chloride In methanol for 1.2h; Reflux; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: p-chloroaniline hydrochloride With hydrogenchloride; sodium nitrite In water at 20℃; Stage #2: 3-oxo-N-[4-(3-oxo-3-phenylpropionylamino)phenyl]-3-phenylpropionamide With pyridine In water at 20℃; for 2h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
69% | Stage #1: p-chloroaniline hydrochloride With hydrogenchloride; sodium nitrite In water Stage #2: 4-hydroxybenzo[h]quinolin-2-(1H)-one With sodium hydroxide In water at 0 - 5℃; for 2h; | 2.6 Preparation of arylazobenzoquinolone dyes 1-10 General procedure: A cold solution of aryldiazonium salt (2.0 mmol) was prepared by adding a solution of NaNO2 (2.2 mmol, 0.15 g into 1.0 mL H2O) to a cold solution of arylamine hydrochloride (2.0 mmol of arylamine in 1.5 mL conc. HCl). The resulting solution of aryldiazonium salt was added drop wise to a mixture of compound (IV) (2.0 mmol, 0.42 g) in water (15 mL) containing NaOH (25 mmol, 1.0 g) at 0-5 °C. The reaction mixture was stirred for 2 h at the same temperature and the precipitate was filtered off and the resulting solid was washed with cold ethanol and dried. The crude product was purified using the recrystallization method as mentioned in Table 1. Under the same reaction conditions, a series substituted arylazobenzoquinolone dyes were obtained in satisfactory yields (Table 1, Scheme 2). When aryldiazonium salts bearing an electron-withdrawing group such as nitro and trifluoromethyl or halogen atom were employed, corresponding arylazobenzoquinolone dyes were obtained with satisfied yields from 60 to 75% (Table 1, entries 1-6). However, when substrates bore an electron donating group such as methyl or ethoxy, the corresponding diazonium salts were very unstable in the reaction mixture and evolution of nitrogen gas was observed during the reaction process, thus only a small quantity of products were isolated in 30-42% yields (Table 1, entries 8-10). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
1: 50% 2: 38% | Stage #1: p-chloroaniline hydrochloride With sodium nitrite In water Stage #2: 3-ethylthio-5-cyanomethyl-4-phenyl-1,2,4-triazole With sodium acetate In ethanol at 20℃; for 24h; | 3.2. General Procedure for the Synthesis of Arylhydrazone (or Arylazo) Compounds 3, 5, 7 and 8 General procedure: A cold solution of aryldiazonium salt (4 mmol) was prepared by adding a sodium nitrite solution (0.4 g, 6 mmol, dissolved in 2 mL water) to a pre-cooled solution of arylamine hydrochloride (4 mmol of either of the appropriate aniline derivatives 2 and 4 in 2 mL of 6 M hydrochloric acid) with continuous stirring. The resulting solution of the aryl diazonium salt was then added carefully to a cold solution of 1,2,4-triazole derivative 1 (4 mmol) in ethanol (40 mL) containing sodium acetate (0.66 gin 2 mL H2O). The reaction mixture was stirred at room temperature for 24 h and the resulting solid product was collected by filtration, washed well with H2O and dried to afford compounds 3B and 5A,respectively, which were purified by preparative TLC using silica gel plates (toluene/acetone, 10:2), followed by recrystallization from EtOH. In the case of the reaction of 1 with 6, the resulting solid product was chromatographed on a preparative TLC plate using 10:3 toluene/acetone as eluent to give two zones. Extraction with acetone followed by recrystallization from EtOH gave compounds 7A and 8B, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
72% | Stage #1: 4-chlorobenzonitrile With hydrogen In ethanol at 25℃; Flow reactor; Stage #2: With hydrogenchloride In ethanol Flow reactor; chemoselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
75% | General procedure: A cold solution of aryldiazonium salt (2.0 mmol) was preparedby adding a solution of NaNO2 (2.2 mmol, 0.15 g into 1.0 mL H2O) toa cold solution of arylamine hydrochloride (2.0 mmol of arylaminein 1.5 mL conc. HCl). The resulting solution of aryl diazonium saltwas added drop wise to a mixture of compound (II) (2.0 mmol,0.43 g) in water (15 mL) containing NaOH (25 mmol, 1.0 g) at0e5 C. The pH of the reaction mixture was maintained at 9e10 byadding 2.5% sodium hydroxide solution. Then, the reaction mixturewas stirred for 2 h at the same temperature and the precipitate wasfiltered off and the resulting solid was washed with cold ethanoland dried at 50 C in an oven. The crude product was purified usingthe recrystallization method as mentioned in Table 1. Under thesame reaction conditions, a series substituted arylazo quinolonedyes were obtained in satisfactory yields (Table 1, Scheme 2). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
96% | With hydrogenchloride In dichloromethane; water at 20℃; | 4.5. Typical procedure for recovery of DPPT from DPPTea-mine adducts General procedure: 4.5. Typical procedure for recovery of DPPT from DPPTea-mine adducts DPPT-p-toluidine (200 mg) was dissolved in CH2Cl2 (5.6 mL).The solution was washed with 1 M HCl aq (5.6 mL3). The organiclayer was concentrated in vacuo and the resulting solid was puri-ed by sublimation at 80 C in vacuo for 12 h to obtain DPPT(128 mg, 93%) as a yellow solid. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
39% | In acetonitrile for 24h; | 10 The 1. 340g (5. Ommol) of 1- (2-methoxyethyl) -2- (nitromethylene) hexahydropyrimidine and 0. 606g (5. Ommol) of p-chloroaniline hydrochloride was added to 20ml of acetonitrile was slowly added dropwise 0. 430g (5. Ommol) of butanediol. After 24 hours of reaction, the solvent was removed by column chromatography to give the pure product as a pale yellow powder, yield 39% |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
60% | Stage #1: p-chloroaniline hydrochloride With hydrogenchloride; sodium nitrite In water at 10℃; for 0.0777778h; Flow reactor; Stage #2: ascorbic acid In water at 20℃; for 0.433333h; Flow reactor; | 3.2. Reactor Configuration for the Synthesis of Hydrazine Derivatives from Diazonium Salts 1-18 General procedure: Three stock solutions were prepared and connected to the flow reactor feed lines for Pumps A-C (see Figure 3 for a pictorial layout). Pump A delivered hydrochloric acid (0.84 M), Pump B a solution of aqueous sodium nitrite (0.98 M) and pump C delivered an aqueous solution of ascorbic acid (0.35 M). In addition a further pump was used to provide the solutions of aniline as their HCl salts dissolved in water (0.35 M). The entire reactor was maintained under positive internal pressure using a 75 psi back pressure regulator at the exit of the reactor. To initiate the reaction each flow channel was pumped at 0.5 mL/min. Progressing through the reactor; Channel A and B were mixed in a Uniqsis mixer chip of 0.27 mL internal volume (16 s residence time) before passing into a 2.75 mL PFA tubular residence coil (165 s residence time). The combined flow was then further united with the aniline solution mixing in a second Uniqsis mixer chip of 2 mL internal volume (80 s residence time). The reacting solution then passed into a 5 mL residence PFA foil coil (150 s residence time, the solution turns pale yellow to orange). The whole initial stage mixing unit was temperature regulated (10° C) using a Polar Bear Plus flow reactor unit. In the second stage reactor the freshly prepared diazonium mixture (combined flow rate 2 mL/min) was united at an Upchurch peek T-mixer with a solution of ascorbic acid delivered from Pump C set at 0.5 mL/min. The flow stream was then progressed into a 52 mL PFA flow coil (20.8 min residence time).The isolation of certain intermediate hydroxamic esters, namely 13-18, could be achieved by immediate extraction of the reactor output with ethyl acetate (5 volumes) and washing the organic phase with sodium hydrogen carbonate (2 M; 2). The organic solution was dried over MgSO4, filtered and concentrated in vacuo to provide a pale yellow solid which was triturated with a 1:1 mixture of hexane and acetone to furnishing the desired product. Alternatively, the output solution was collected and left to stir for 1 h to ensure complete hydrolysis to the corresponding oxamic acid, 1-12, had occurred. The products were isolated by basification of the reaction mixture pH ~9 followed by extraction with EtOAc (3 volumes). The aqueous solution was then acidified to pH ~4 and extracted with EtOAc (3 volumes), the organic phase was dried over MgSO4, the solvent evaporated to yield compounds 1-12. Note: for compounds 1-12 a proton signal sites under the residual DMSO signal. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
35% | In isopropyl alcohol for 1h; Reflux; | N-[(1-Phenyl-1H-imidazo[1,2-a]indol-9-yl)methylidene]-anilinium chloride (21a). General procedure: Benzenaminium chloride (648 mg,5.0 mmol) was added to compound 12 (700 mg, 2.5 mmol)in 2-propanol (3 ml). The reaction mixture was refluxed,and a product began to precipitate within 1 h. The precipitatethat formed was filtered off, washed with 2-propanoland petroleum ether, and dried to give the crude product. Yield after recrystallization from 2-propanol 340 mg (49%).Spectroscopically pure substance was obtained by secondrecrystallization from 2-propanol. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
58% | [2025] A solution of 4-chloroaniline hydrochloride (0.600 g, 3.658 mmol) and sodium hydride (60.00 %, 0.154 g, 3.841 mmol) in N,N-dimethylformamide ( 10 mL) was stirred at 0 C for 10 min, and mixed with <strong>[128577-47-9]methyl 4-(bromomethyl)-3-fluorobenzoate</strong> (0.994 g, 4.024 mmol). The reaction mixture was stirred at the same temperature for additional 1 hr, and quenched at the room temperature by the addition of saturated aqueous sodium bicarbonate solution ( 10 mL, 10 min stirring). Then, water was added to the reaction mixture, followed by extraction with dichloromethane. The bi-phasic mixture was passed through a plastic frit to remove solid residues and aqueous layer, and the organic layer collected was concentrated in vacuo. The concentrate was purified and concentrated by column chromatography (Si02, 12 g cartridge; ethyl acetate / hexane = 0 % to 20 ) to give the title compound methyl 4-(((4-chlorophenyl)amino)methyl)-3-fluorobenzoate as pale yellow solid (0.623 g, 58.0 %). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
65% | With 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical In N,N-dimethyl-formamide at 50℃; Green chemistry; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
78% | Stage #1: p-chloroaniline hydrochloride With sodium nitrite In water; acetone for 0.25h; Stage #2: methyl 2-(benzyloxycarbonylamino)acrylate In water; acetone at 0℃; for 0.333333h; Stage #3: With ferrocene In water; acetone at 0℃; for 1h; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
With triethylamine In dichloromethane at 20℃; for 3h; Inert atmosphere; | General procedure for the preparation of 4-18 General procedure: To a solution of compound 27 (1 mmol) in 20 mL dried CH2Cl2 was added oxalyl chloride (4 mmol). The mixture was stirred at room temperature for 24 h under argon and then concentrated to dryness under reduced pressure. Hexane (3 * 10 mL) was added to the residue, then concentrated under vacuum to dryness. To a dried CH2Cl2 (20 mL) solution of aniline hydrochloride, 4-methoxyaniline hydrochloride, 4-(trifluoromethoxy)aniline hydrochloride, 4-fluoroaniline hydrochloride, 4-chloroaniline hydrochloride, 4-bromoaniline hydrochloride, 3-methoxyaniline hydrochloride, 3-chloroaniline hydrochloride, 2-methoxyaniline hydrochloride, 2-chloroaniline hydrochloride, benzylamine hydrochloride, 4-methoxybenzylamine hydrochloride, N,N-Dimethylethylenediamine, or pyrrolidine (1.5 mmol) was added to the above acid chloride in the presence of triethylamine (3.0 mmol). The reaction mixture was stirred at room temperature for 3 h under argon and then concentrated. The obtained residue was dissolved in 2:1 MeOH/CH2Cl2 (15 mL) and then NaOMe was added until pH = 10. After stirred at r.t. for 12 h, the solution was neutralized with Dowex 50 * 8 (H+) resin until pH = 7, filtered and concentrated under vacuum. Then the residue was purified by silica gel column chromatography (CH2Cl2-MeOH, 6:1) to give compounds 4-18, respectively. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
Stage #1: p-chloroaniline hydrochloride With sodium nitrite In water at 10℃; for 0.5h; Stage #2: dicyandiamide With sodium carbonate In water at 20 - 60℃; for 2h; | 1.1-1.2; 2.1-2.2; 3.1-3.2; 4.1-4.2; 5.1-5.2; 6.1-6.2 Example 1 (1) Preparation of p-chlorobenzenediazonium chloride Weigh 4-chloroaniline (3.83g, 0.03mol), polyethylene glycol-600 (0.10g), measure 15mL (0.072mol) of 16% hydrochloric acid in a 150mL three-necked flask,Dissolve in a water bath at 60°C.Stir for 10 minutes, then put it in a cold water bath to precipitate 4-chloroaniline hydrochloride fine particles, add ice to keep the temperature below 10°C,Slowly add sodium nitrite solution (2.24g, 0.0324mol, add 8mL deionized water to dissolve).After stirring and reacting for 0.5h, a p-chlorobenzene diazonium chloride solution was obtained.Use starch-KI test paper to remove excess nitrous acid with urea.(2) Synthesis of 1-(4-chlorophenyl)-3-cyanoguanidine Weigh dicyandiamide (2.65g, 0.0315mol) and anhydrous sodium carbonate (0.95g, 0.009mol) in a beaker,Add 40mL deionized water and dissolve in a 60 water bath.Add the mixed solution slowly from the constant pressure dropping funnel to the above-mentioned p-chlorobenzene diazonium chloride solution,The reaction was stirred at 20°C for 2h; after that, the wet product was separated by suction filtration, and put into 16% dilute hydrochloric acid, and nitrogen was placed in a water bath at 70°C for 2h.Then the crude product is obtained by suction filtration, and it is heated and dissolved in 8% sodium hydroxide solution.Use activated carbon to decolorize, remove the activated carbon by suction filtration, add appropriate amount of hydrochloric acid to neutralize,After the solid is separated out, it is filtered and washed with suction, and dried to obtain the product 1-(4-chlorophenyl)-3-cyanoguanidine. The calculated yield is 82.1% by weighing. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
71% | With bis[tri(2-methoxyphenyl)phosphine]palladium(II) dichloride In tetrahydrofuran at 110℃; for 24h; Autoclave; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
94% | With bis-triphenylphosphine-palladium(II) chloride In tetrahydrofuran at 110℃; for 24h; Autoclave; regioselective reaction; |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
97% | With triethylamine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; | Intermediate Cl To a solution of 4-chloroaniline HCI salt (10.0 g, 61.0 mmol) in anhydrous CH2CI2 (100 mL) was added NEta (10.2 mL, 73.2 mmol). The solution was cooled to 0 °C and chloroacetylchloride (5.80 mL, 73.2 mmol) was added dropwise. The light brown suspension was stirred at room temperature under argon for 16 h. The reaction mixture was washed with H2O (2x30 mL) and 0.5 N HCI solution (1x25 mL). The organic layer was dried over NaaSO4 and concentrated to yield Cl as a light grey solid (12.0 g, 97%). 1H-NMR (300 MHz, CDCIa) 6: 8.21 (br s, 1H), 7.54-7.47 (m, 2H), 7.36-7.29 (m, 2H), 4.19 (s, 2H). UPLC-ESI (m/z): 204, 206, 208 [M+H]+. |
97% | With triethylamine In dichloromethane at 0 - 20℃; for 16h; Inert atmosphere; | Intermediate Cl To a solution of 4-chloroaniline HCI salt (10.0 g, 61.0 mmol) in anhydrous CH2CI2 (100 mL) was added NEta (10.2 mL, 73.2 mmol). The solution was cooled to 0 °C and chloroacetylchloride (5.80 mL, 73.2 mmol) was added dropwise. The light brown suspension was stirred at room temperature under argon for 16 h. The reaction mixture was washed with H2O (2x30 mL) and 0.5 N HCI solution (1x25 mL). The organic layer was dried over NaaSO4 and concentrated to yield Cl as a light grey solid (12.0 g, 97%). 1H-NMR (300 MHz, CDCIa) 6: 8.21 (br s, 1H), 7.54-7.47 (m, 2H), 7.36-7.29 (m, 2H), 4.19 (s, 2H). UPLC-ESI (m/z): 204, 206, 208 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
62% | With benzotriazol-1-ol; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere; | Intermediate G1 Boc-L-Pro (1.00 g, 4.65 mmol), 4-chloroaniline hydrochloride (838 mg, 5.11 mmol), EDC*HCI (2.22 g, 11.6 mmol) and HOBt (1.07 g, 6.98 mmol) were suspended in anhydrous CH2CI2 (30 mL). The suspension was cooled to 0°C, and EtaN (2.33 mL, 16.7 mmol) was added. The resulting light brown solution was stirred at room temperature under argon for 3h. To the mixture was added H2O (15 mL), the resulting mixture was extracted with CH2CI2 (3x20 mL), the organic layer was dried over Na2SO4 and evaporated. The crude product was purified by reversed phase column flash chromatography on C-18-SH modified silica gel (10 - 85 % MeCN in H2O) to yield G1 as a white solid (931 mg, 62%). 1H NMR (CDCk, 300 MHz) 6: 9.62 (s, 1H), 7.49-7.42 (m, 2H), 7.29-7.19 (m, 2H), 4.53-4.34 (m, 1H), 3.52-3.28 (m, 2H), 2.61-2.40 (m, 1H), 2.06-1.84 (m, 3H), 1.49 (s, 9H). UPLC-ESI (m/z): 323, 325 [M-H]'. |
62% | With benzotriazol-1-ol; N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride; triethylamine In dichloromethane at 0 - 20℃; for 3h; Inert atmosphere; | Intermediate G1 Boc-L-Pro (1.00 g, 4.65 mmol), 4-chloroaniline hydrochloride (838 mg, 5.11 mmol), EDC*HCI (2.22 g, 11.6 mmol) and HOBt (1.07 g, 6.98 mmol) were suspended in anhydrous CH2CI2 (30 mL). The suspension was cooled to 0°C, and EtaN (2.33 mL, 16.7 mmol) was added. The resulting light brown solution was stirred at room temperature under argon for 3h. To the mixture was added H2O (15 mL), the resulting mixture was extracted with CH2CI2 (3x20 mL), the organic layer was dried over Na2SO4 and evaporated. The crude product was purified by reversed phase column flash chromatography on C-18-SH modified silica gel (10 - 85 % MeCN in H2O) to yield G1 as a white solid (931 mg, 62%). 1H NMR (CDCk, 300 MHz) 6: 9.62 (s, 1H), 7.49-7.42 (m, 2H), 7.29-7.19 (m, 2H), 4.53-4.34 (m, 1H), 3.52-3.28 (m, 2H), 2.61-2.40 (m, 1H), 2.06-1.84 (m, 3H), 1.49 (s, 9H). UPLC-ESI (m/z): 323, 325 [M-H]'. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
85% | Stage #1: Benzo[b]thiophene-2-carboxylic acid; p-chloroaniline hydrochloride With 4-methyl-morpholine; 4-dimethylaminopyridine In dichloromethane at 20℃; Stage #2: With N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃; | Compound 65 Benzo[b]thiophene-2-carboxylic acid (900 mg, 5.05 mmol), 4-chloroaniline hydrochloride (870 mg, 5.30 mmol) and DMAP (250 mg, 2.02 mmol) were dissolved in CH2CI2 (30 mL). NMM (920 mg, 9.09 mmol) was added and reaction mixture was stirred 10 min at room temperature. 3-(Ethyliminomethyleneamino)-/V,//-dimethylpropan-l-amine hydrochloride (1.45 g, 7.58 mmol) was added in one portion and the resulting solution was stirred at room temperature for 16 h. The resulting suspension was evaporated in vacuo and the residue suspended in a small amount of CH2CI2. The solids were collected by filtration and washed with a minimum of CH2CI2 to give desired product as a white solid (1.23 g, 85%). 1H-NMR (300 MHz, DMSO-dg): 10.63 (s, 1H), 8.38-8.35 (m, 1H), 8.10-7.98 (m, 2H), 7.85-7.77 (m, 2H), 7.54-7.40 (m, 4H). UPLC-ESI (m/z): 288, 290 [M+H]+. |
85% | Stage #1: Benzo[b]thiophene-2-carboxylic acid; p-chloroaniline hydrochloride With 4-methyl-morpholine; 4-dimethylaminopyridine In dichloromethane at 20℃; Stage #2: With N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃; | Compound 65 Benzo[b]thiophene-2-carboxylic acid (900 mg, 5.05 mmol), 4-chloroaniline hydrochloride (870 mg, 5.30 mmol) and DMAP (250 mg, 2.02 mmol) were dissolved in CH2CI2 (30 mL). NMM (920 mg, 9.09 mmol) was added and reaction mixture was stirred 10 min at room temperature. 3-(Ethyliminomethyleneamino)-/V,//-dimethylpropan-l-amine hydrochloride (1.45 g, 7.58 mmol) was added in one portion and the resulting solution was stirred at room temperature for 16 h. The resulting suspension was evaporated in vacuo and the residue suspended in a small amount of CH2CI2. The solids were collected by filtration and washed with a minimum of CH2CI2 to give desired product as a white solid (1.23 g, 85%). 1H-NMR (300 MHz, DMSO-dg): 10.63 (s, 1H), 8.38-8.35 (m, 1H), 8.10-7.98 (m, 2H), 7.85-7.77 (m, 2H), 7.54-7.40 (m, 4H). UPLC-ESI (m/z): 288, 290 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: 5-bromothieno[2,3-b]pyridine-2-carboxylic acid; p-chloroaniline hydrochloride With 4-methyl-morpholine; benzotriazol-1-ol In dichloromethane at 20℃; for 0.166667h; Stage #2: With N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃; for 16h; | 5-bromo-N-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide (N3) 5-Bromothieno[2,3-b]pyridine-2-carboxylic acid (1.00 g, 3.87 mmol), 4-chloroaniline hydrochloride (700 mg, 4.26 mmol) and HOBt-F O (300 mg, 1.94 mmol) were suspended in anhydrous CH2CI2 (20 mL). N-methyl morpholine (780 mg, 7.75 mmol) was added and the reaction mixture was stirred at room temperature for 10 min. 3-(Ethyliminomethyleneamino)-/V,//-dimethylpropan-l-amine hydrochloride (1.11 g, 5.81 mmol) was added in one portion and the resulting solution was stirred at room temperature for 16 h. The resulting suspension was evaporated under reduced pressure, and the residue was suspended in a small amount of 1,2-dichloromethane. The solids were collected by filtration and washed with minimum CH2CI2 to give the desired product as a white solid (1.14 g, 80%). XH NMR (300 MHz, DMSO-dg) 6: 10.81 (s, 1H), 8.79 (s, 2H), 8.31 (s, 1H), 7.83-7.77 (m, 2H), 7.49-7.41 (m, 2H). |
80% | Stage #1: 5-bromothieno[2,3-b]pyridine-2-carboxylic acid; p-chloroaniline hydrochloride With 4-methyl-morpholine; benzotriazol-1-ol In dichloromethane at 20℃; for 0.166667h; Stage #2: With N-[3-(N,N-dimethylamino)-propyl]-N'-ethyl-carbodiimide hydrochloride In dichloromethane at 20℃; for 16h; | 5-bromo-N-(4-chlorophenyl)thieno[2,3-b]pyridine-2-carboxamide (N3) 5-Bromothieno[2,3-b]pyridine-2-carboxylic acid (1.00 g, 3.87 mmol), 4-chloroaniline hydrochloride (700 mg, 4.26 mmol) and HOBt-F O (300 mg, 1.94 mmol) were suspended in anhydrous CH2CI2 (20 mL). N-methyl morpholine (780 mg, 7.75 mmol) was added and the reaction mixture was stirred at room temperature for 10 min. 3-(Ethyliminomethyleneamino)-/V,//-dimethylpropan-l-amine hydrochloride (1.11 g, 5.81 mmol) was added in one portion and the resulting solution was stirred at room temperature for 16 h. The resulting suspension was evaporated under reduced pressure, and the residue was suspended in a small amount of 1,2-dichloromethane. The solids were collected by filtration and washed with minimum CH2CI2 to give the desired product as a white solid (1.14 g, 80%). XH NMR (300 MHz, DMSO-dg) 6: 10.81 (s, 1H), 8.79 (s, 2H), 8.31 (s, 1H), 7.83-7.77 (m, 2H), 7.49-7.41 (m, 2H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
80% | Stage #1: p-chloroaniline hydrochloride With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: ϒ-butyrolactone In tetrahydrofuran; hexane at 20℃; for 1.5h; | Intermediate E2 4-Chloroaniline hydrochloride (1.50 g, 9.14 mmol) was dissolved in anhydrous THF (35 mL). The solution was cooled to -78°C and 2.5M n-BuLi solution in hexanes (9.2 mL, 22.9 mmol) was added dropwise. The resulting light brown solution was stirred at -78°C under argon for 30 min. To the mixture was added y-butyrolactone (1.12 mL, 13.7 mmol). The resulting solution was stirred at room temperature for 1.5 h. The reaction was quenched by addition of aq. sat. NH4CI solution (20 mL). The resulting mixture was extracted with EtOAc (3xl5mL), the organic layer was dried over NajSCU and evaporated. The crude was recrystallized from EtjO to yield DI as a white solid (1.57 g, 80%). 1H NMR (CDCk, 300 MHz) 6: 7.64 (s, 1H), 7.49-7.42 (m, 2H), 7.30-7.24 (m, 2H), 3.77 (t, 7=5.7 Hz, 2H), 2.53 (t, 7=6.9 Hz, 2H), 2.23-2.10 (m,), 2.03-1.92 (m, 2H). UPLC-ESI (m/z): 214, 216 [M+H]+. |
80% | Stage #1: p-chloroaniline hydrochloride With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #2: ϒ-butyrolactone In tetrahydrofuran; hexane at 20℃; for 1.5h; | Intermediate E2 4-Chloroaniline hydrochloride (1.50 g, 9.14 mmol) was dissolved in anhydrous THF (35 mL). The solution was cooled to -78°C and 2.5M n-BuLi solution in hexanes (9.2 mL, 22.9 mmol) was added dropwise. The resulting light brown solution was stirred at -78°C under argon for 30 min. To the mixture was added y-butyrolactone (1.12 mL, 13.7 mmol). The resulting solution was stirred at room temperature for 1.5 h. The reaction was quenched by addition of aq. sat. NH4CI solution (20 mL). The resulting mixture was extracted with EtOAc (3xl5mL), the organic layer was dried over NajSCU and evaporated. The crude was recrystallized from EtjO to yield DI as a white solid (1.57 g, 80%). 1H NMR (CDCk, 300 MHz) 6: 7.64 (s, 1H), 7.49-7.42 (m, 2H), 7.30-7.24 (m, 2H), 3.77 (t, 7=5.7 Hz, 2H), 2.53 (t, 7=6.9 Hz, 2H), 2.23-2.10 (m,), 2.03-1.92 (m, 2H). UPLC-ESI (m/z): 214, 216 [M+H]+. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
61% | In 2-ethoxy-ethanol for 15h; Reflux; | 2 Synthesize 3-3 The preparation method of 3-3, is characterized in that, comprises the steps: take by weighing monomer M2 (bis-hydrochloride form, 2.03g, 7.51mmol, 1eq) and p-aminochlorobenzene (hydrochloride form, 2.45g, 14.94 g) mmol, 2eq), then the solvent ethylene glycol ether was added to reflux for 15h. The mixture obtained after the reaction was washed three times with ethylene glycol ether and glacial ethanol precipitation. The resulting solid was dried in vacuo to give a white powder (2.73 g, 61%). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
89% | In chloroform at 50℃; for 12h; | Synthesis of 1 General procedure: A mixture of 3-tert-butylamino-2-nitropropenal 3 (172 mg, 1.0 mmol), arylamine (1.4 mmol), andarylammonium chloride (1.0 mmol) was stirred in chloroform (5 mL) for 12 h at 50 °C. Thereaction mixture was then diluted with chloroform and washed with water (10 mL) for threetimes. The organic phase was dried over MgSO4 and filtered. The solution was evaporated anddried under vacuum to give a yellow solid. The crude product was purified throughrecrystallization (CH2Cl2/n-hexane) to give yellow-colored crystals of 1. |
Tags: 20265-96-7 synthesis path| 20265-96-7 SDS| 20265-96-7 COA| 20265-96-7 purity| 20265-96-7 application| 20265-96-7 NMR| 20265-96-7 COA| 20265-96-7 structure
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P250 | Do not subject to grinding/shock/friction. |
P251 | Pressurized container: Do not pierce or burn, even after use. |
P260 | Do not breathe dust/fume/gas/mist/vapours/spray. |
P261 | Avoid breathing dust/fume/gas/mist/vapours/spray. |
P262 | Do not get in eyes, on skin, or on clothing. |
P263 | Avoid contact during pregnancy/while nursing. |
P264 | Wash hands thoroughly after handling. |
P265 | Wash skin thouroughly after handling. |
P270 | Do not eat, drink or smoke when using this product. |
P271 | Use only outdoors or in a well-ventilated area. |
P272 | Contaminated work clothing should not be allowed out of the workplace. |
P273 | Avoid release to the environment. |
P280 | Wear protective gloves/protective clothing/eye protection/face protection. |
P281 | Use personal protective equipment as required. |
P282 | Wear cold insulating gloves/face shield/eye protection. |
P283 | Wear fire/flame resistant/retardant clothing. |
P284 | Wear respiratory protection. |
P285 | In case of inadequate ventilation wear respiratory protection. |
P231 + P232 | Handle under inert gas. Protect from moisture. |
P235 + P410 | Keep cool. Protect from sunlight. |
Response | |
Code | Phrase |
P301 | IF SWALLOWED: |
P304 | IF INHALED: |
P305 | IF IN EYES: |
P306 | IF ON CLOTHING: |
P307 | IF exposed: |
P308 | IF exposed or concerned: |
P309 | IF exposed or if you feel unwell: |
P310 | Immediately call a POISON CENTER or doctor/physician. |
P311 | Call a POISON CENTER or doctor/physician. |
P312 | Call a POISON CENTER or doctor/physician if you feel unwell. |
P313 | Get medical advice/attention. |
P314 | Get medical advice/attention if you feel unwell. |
P315 | Get immediate medical advice/attention. |
P320 | |
P302 + P352 | IF ON SKIN: wash with plenty of soap and water. |
P321 | |
P322 | |
P330 | Rinse mouth. |
P331 | Do NOT induce vomiting. |
P332 | IF SKIN irritation occurs: |
P333 | If skin irritation or rash occurs: |
P334 | Immerse in cool water/wrap n wet bandages. |
P335 | Brush off loose particles from skin. |
P336 | Thaw frosted parts with lukewarm water. Do not rub affected area. |
P337 | If eye irritation persists: |
P338 | Remove contact lenses, if present and easy to do. Continue rinsing. |
P340 | Remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P341 | If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P342 | If experiencing respiratory symptoms: |
P350 | Gently wash with plenty of soap and water. |
P351 | Rinse cautiously with water for several minutes. |
P352 | Wash with plenty of soap and water. |
P353 | Rinse skin with water/shower. |
P360 | Rinse immediately contaminated clothing and skin with plenty of water before removing clothes. |
P361 | Remove/Take off immediately all contaminated clothing. |
P362 | Take off contaminated clothing and wash before reuse. |
P363 | Wash contaminated clothing before reuse. |
P370 | In case of fire: |
P371 | In case of major fire and large quantities: |
P372 | Explosion risk in case of fire. |
P373 | DO NOT fight fire when fire reaches explosives. |
P374 | Fight fire with normal precautions from a reasonable distance. |
P376 | Stop leak if safe to do so. Oxidising gases (section 2.4) 1 |
P377 | Leaking gas fire: Do not extinguish, unless leak can be stopped safely. |
P378 | |
P380 | Evacuate area. |
P381 | Eliminate all ignition sources if safe to do so. |
P390 | Absorb spillage to prevent material damage. |
P391 | Collect spillage. Hazardous to the aquatic environment |
P301 + P310 | IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician. |
P301 + P312 | IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell. |
P301 + P330 + P331 | IF SWALLOWED: Rinse mouth. Do NOT induce vomiting. |
P302 + P334 | IF ON SKIN: Immerse in cool water/wrap in wet bandages. |
P302 + P350 | IF ON SKIN: Gently wash with plenty of soap and water. |
P303 + P361 + P353 | IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower. |
P304 + P312 | IF INHALED: Call a POISON CENTER or doctor/physician if you feel unwell. |
P304 + P340 | IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing. |
P304 + P341 | IF INHALED: If breathing is difficult, remove victim to fresh air and keep at rest in a position comfortable for breathing. |
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P306 + P360 | IF ON CLOTHING: Rinse Immediately contaminated CLOTHING and SKIN with plenty of water before removing clothes. |
P307 + P311 | IF exposed: call a POISON CENTER or doctor/physician. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P309 + P311 | IF exposed or if you feel unwell: call a POISON CENTER or doctor/physician. |
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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