Structure of 696-08-2
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CAS No. : | 696-08-2 |
Formula : | C6H6ClNO |
M.W : | 143.57 |
SMILES Code : | [O-][N+]1=CC=C(Cl)C=C1C |
MDL No. : | MFCD09033257 |
GHS Pictogram: |
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Signal Word: | Warning |
Hazard Statements: | H315-H319-H335 |
Precautionary Statements: | P261-P264-P271-P280-P302+P352-P304+P340-P305+P351+P338-P312-P362-P403+P233-P501 |
* 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 |
---|---|---|
In dichloromethane; | i) Production of 4-chloro-2-cyano-6-methylpyridine 32 g (223 mmol) of 4-chloro-2-methylpyridine-1-oxide was dissolved in 250 ml of methylene chloride. The resultant solution was added with 24. 6 g (248 mmol) of trimethyl silylanilide at a room temperature in a manner of spending 5 min. The mixture was stirred for 10 min. and then added with 23. 5 g (219 mmol) of dimethylcarbamoyl chloride at the same temperature in a manner of spending 5 min. At that time, the inner temperature of the mixture had elevated to the reflux temperature thereof due to heat generated by the reaction. While stirring the mixture, the mixture was naturally cooled until the time that the inner temperature of the mixture falls to reach a room temperature. After stirring the mixture for 4 days, the reacted solution was cooled so as to maintain the temperature thereof at 5 C. and was added with 300 ml of 10% aqueous solution of sodium hydrogen atomcarbonate. The organic layer of the mixture was separated, and the aqueous layer was extracted with chloroform. The obtained chloroform layer was unified with the separated organic layer, and the unified mixture was dried with anhydrous magnesium sulfate and then condensed under reduced pressure to obtain a crude product. The obtained crude product was then purified by means of silica gel column chromatography (elude; hexane:ethyl acetate=4:1 (v/v)) to obtain the target compound in an amount of 10 g. 1H-NMR (CDCl3, TMS, delta ppm) data; 2.60 (s, 3H), 7.40 (d, 1H), 7.53 (d, 1H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
84% | With triethylamine; at 20℃; for 44h;Reflux; | To a solution of intermediate 1A (128.0 g, 889 mmol) and triethylamine (260 ml) in propionitrile (1.5 1) was added trimethylsilyl cyanide (334 ml, 2.67 mol). The mixture was stirred at reflux for26 h then left to stand at room temperature for 18 h. The reaction was quenched by the addition of30% aqueous potassium carbonate solution and the layers were separated. The organic layer was washed with 10% aqueous potassium carbonate solution, brine, dried over magnesium sulfate, filtered and concentrated. The resulting dark solid was recrystallized from hot isopropanol (150 ml) and water (300 ml) to give intermediate 2A (114.3 g, 84%). |
75% | c. PREPARATION OF 4-CHLORO-6-METHYLPICOLINONITRILE.[00398] 4-chloro-2-methylpyridine-N-oxide (8.97g, 62.5 mmol, 1 .00 eq) was dissolved in CH2C12 and dried over MgSO^. The solution was added to a flame-dried round-bottom flask and CH2C12 was added to give a total volume of 188 mL. TMS-cyanide (10 mL, 75 mmol, 1.2 eq) was added and the reaction stirred for 1 5 minutes. Dimethylcarbamyl chloride (6.9 mL, 75 mmol, 1.2 eq) was added dropwise over 20 minutes, and the reaction was stirred for 24 hours. An additional one equivalent each of TMS-cyanide and dimethylcarbamyl chloride were added and the reaction was stirred for another 72 hours. The reaction was made basic with 10% K2C03 and extraxcted with CH2C12 (3 ). The combined organics were dried (MgS04), filtered and concentrated in vacuo. Purification by flash chromatography on silica gel afforded 7.2 g (75%) of the title compound as a white solid. NMR (400 MHz, OMSO-d6) delta 8.13 (d, J= 1 .6 Hz, 1), 7.82 (d, J= 1.7 Hz, 1H), 2.52 (s, 3H); ES-MS [M+l ]+: | |
75% | With magnesium sulfate; N,N-Dimethylcarbamoyl chloride; In dichloromethane; for 96.5833h; | b. SYNTHESIS OF 4-CHLORO-6-METHYLPICOLINONITRILE (COMPOUND 2)Compound 1 (8.97 g, 62.5 mmol, 1.00 eq) was dissolved in CH2Cl2 and dried over MgSO4. The solution was added to a flame-dried round-bottom flask and CH2Cl2 was added to give a total volume of 188 mL. TMS-cyanide (10 mL, 75 mmol, 1.2 eq) was added and the reaction stirred for 15 minutes. Dimethylcarbamoyl chloride (6.9 mL, 75 mmol, 1.2 eq) was added dropwise over 20 minutes, and the reaction was stirred for 24 hours. An additional one equivalent each of TMS-cyanide and Dimethylcarbamoyl chloride was added and the reaction was stirred for another 72 hours. The reaction was made basic with 10% K2CO3 and extracted with CH2Cl2 (3x). The combined organics were dried (MgSO4), filtered and concentrated in vacuo. Purification by flash chromatography on silica gel afforded 7.2 g (75%) of the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) delta 8.13 (d, J = 1.6 Hz, 1H), 7.82 (d, J = 1.7 Hz, 1 H), 2.52 (s, 3H); ES-MS [M+1]+: 153.2. |
51% | To a solution of 4-chloro-2-methylpyridine-N-oxide(7, 4.3 kg, 29.94 mol) in dichloromethane (64.5 L, 15 V) was added trimethylsilyl cyanide (9.76 L, 77.83 mol) at 25-30 C over a period of 30 min and furtherstirred for 15 min. Reaction mass was cooled to 0-5 C. N,NDimethylcarbamoylchloride (7.17 L, 77.83 mol) was added drop wise over aperiod of 1 h. The reaction mass was slowly warmed to 25-30 C and stirred for36 h. Reaction was monitored by HPLC [7 NMT 1.0%]. The reaction mass wascooled to 0-5 C. The reaction was quenched with 10% aqueous potassiumcarbonate solution until the pH of aqueous layer was about 9-10. Thetemperature of reaction mass was allowed to attain 25-30 C and the layerswere separated. The aqueous layer was extracted with dichloromethane (8.6 L,2 V). The combined organic layer was washed with 0.5 N HCl solution (21.5 L,5 V) followed by brine solution (21.5 L, 5 V), dried over anhydrous sodiumsulfate and concentrated under vacuum. The residue was chased twice with nheptane(2 17.2 L). The crude product was diluted with 2% ethyl acetate[Ashok alco-chem limited, Purity (area%) by GC - 100%] in hexanes (43 L, 10 V)and filtered through silica plug (21.5 kg, 5% w/w on SM, 230-400 mesh) andsilica plug was washed with 10% ethyl acetate in hexanes till the product was completely eluted (300 L, 69 V). Combined fractions were concentrated andresidue was chased twice with n-heptane (2 17.2 L). Resulting mass wasstirred in n-heptane (21.5 L, 5 V) at 0-5 C for 1 h and filtered. Solid waswashed with cold n-heptane (4.3 L, 1 V) and dried to get 8 as off white solid(2.32 kg, 51%).. 1H NMR (400 MHz, DMSO-d6) d 8.13 (d, J = 1.6 Hz, 1H), 7.82 (d,J = 1.7 Hz, 1H), 2.52 (s, 3H); 13C NMR (100 MHz, DMSO-d6) d = 161.99, 144.13,133.01, 127.65, 126.40, 116.60, 23.57 ppm; LCMS (Method 1): RT = 0.715 min,m/z = 153.2 [M + H]+; HRMS, calc?d for C7H5ClN2 [M], 152.0141; found152.0139. | |
With triethylamine; In acetonitrile;Reflux; | b) To a solution of 4-chloro-2-methyl-pyridine 1 -oxide (2.250 g, 15.67 mmol) in acetonitrile (50 ml) was added Et3N (6.55 ml, 47.0 mmol,) and TMSCN (1 1.76 ml, 94.03 mmol). The resulting brown solution was heated overnight under reflux and then quenched with 60 mL of sat. aqueous NaHC03. The aqueous phase was extracted with CH2CI2 and the combined organic layers were washed with water and brine, dried over Na2S04 and concentrated under reduced pressure. The residue was purified by flash column chromatography (cyclohexane/AcOEt; 100/0 to 0/100) to afford 4-chloro-6-methyl-pyridine-2-carbonitrile as a light orange powder.LCMS: 1.35 min; method A; [M+H]+ = 153 |
Tags: 696-08-2 synthesis path| 696-08-2 SDS| 696-08-2 COA| 696-08-2 purity| 696-08-2 application| 696-08-2 NMR| 696-08-2 COA| 696-08-2 structure
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