* 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.
Reference：
[1] Chemical and Pharmaceutical Bulletin, 1986, vol. 34, # 4, p. 1485 - 1492
[2] Chemical and Pharmaceutical Bulletin, 1986, vol. 34, # 4, p. 1485 - 1492
2
[ 15177-57-8 ]
[ 7677-24-9 ]
[ 85331-33-5 ]
Yield
Reaction Conditions
Operation in experiment
40.2%
With N,N-Dimethylcarbamoyl chloride In dichloromethane at 20℃; for 48 h;
[0166] 21.8 ml (0.174 mmol) of trimethylsilyl cyanide and 14.6 ml (0.158 mmol) of dimethylcarbamoyl chloride are added successively to a solution of 26 g (0.158 mol) of 3,5-dichloropyridine 1-oxide (Johnson et al., J. Chem. Soc. B, 1967, 1211) in 80 ml of dichloromethane and stirred at room temperature for 48 hours. 100 ml of a 10percent strength aqueous NaHCO3 solution are added, and the mixture is vigorously stirred for 10 minutes. Separation of the phases is followed by extraction once with dichloromethane; the combined organic phases are dried and concentrated. The residue is chromatographed on silica gel with dichloromethane and recrystallized from a little methanol. [0167] 11 g (40.2percent) of 2-cyano-3,5-dichloropyridine (melting point: 102° C.) are obtained.
EXAMPLE 27A 2-Cyano-3,5-dichloropyridine 3,5-Dichloropyridine-N-oxide (10.0 g, 61 mmol), trimethysilylcyanide (25 mL, 183 mmol) and triethylamine (17 mL, 122 mmol) combined in acetonitrile (60 mL) and heated to reflux for 6 hr. The solvent was evaporated and the residue was partitioned between diethyl ether and 5percent aq. NaHCO3. The organic phase was dried (MgSO4), evaporated, and the product purified by chromatography over silica gel to yield 10.0 g (97percent) of the title compound: 1 H NMR (300 MHz, CDCl3) δ 7.92 (d, 1H), 8.58 (d, 1H).
Reference：
[1] Patent: US6046207, 2000, A,
[2] Patent: US5891882, 1999, A,
With peracetic acid In chloroform; acetic acid at 50℃; for 67h;
94%
With dihydrogen peroxide; methyltrioxorhenium(VII) In dichloromethane; water at 24℃; for 17h;
90%
With bis-trimethylsilanyl peroxide; per-rhenic acid In dichloromethane; water at 24℃; for 20h;
78%
With 3-chloro-benzenecarboperoxoic acid In dichloromethane at 0 - 20℃;
70%
With dihydrogen peroxide In dichloromethane for 17h;
With dihydrogen peroxide
2 Example 2:
Pyridine-3,5-disulfonic acid is made from 3,5-dichloro-pyridine which is transformed into 3,5-dichloro-pyridine-N-oxide with H2O2. This compound is treated at 135°C in an autoclave with an excess of Na2SC>3, resulting in the sodium salt of pyridine-3,5-disulfonic acid-N-oxide which is reduced by NaBH4 to yield the sodium salt of pyridine-3,5-disulfonic acid. The disalt is alkylated with methyl methanesulfonate to yield sodium [3,5-disulfonato-1 -methyl-pyridinium].
With N,N-Dimethylcarbamoyl chloride; In dichloromethane; at 20℃; for 48h;
[0166] 21.8 ml (0.174 mmol) of trimethylsilyl cyanide and 14.6 ml (0.158 mmol) of dimethylcarbamoyl chloride are added successively to a solution of 26 g (0.158 mol) of 3,5-dichloropyridine 1-oxide (Johnson et al., J. Chem. Soc. B, 1967, 1211) in 80 ml of dichloromethane and stirred at room temperature for 48 hours. 100 ml of a 10% strength aqueous NaHCO3 solution are added, and the mixture is vigorously stirred for 10 minutes. Separation of the phases is followed by extraction once with dichloromethane; the combined organic phases are dried and concentrated. The residue is chromatographed on silica gel with dichloromethane and recrystallized from a little methanol. [0167] 11 g (40.2%) of 2-cyano-3,5-dichloropyridine (melting point: 102 C.) are obtained.
EXAMPLE 27A 2-Cyano-3,5-dichloropyridine 3,5-Dichloropyridine-N-oxide (10.0 g, 61 mmol), trimethysilylcyanide (25 mL, 183 mmol) and triethylamine (17 mL, 122 mmol) combined in acetonitrile (60 mL) and heated to reflux for 6 hr. The solvent was evaporated and the residue was partitioned between diethyl ether and 5% aq. NaHCO3. The organic phase was dried (MgSO4), evaporated, and the product purified by chromatography over silica gel to yield 10.0 g (97%) of the title compound: 1 H NMR (300 MHz, CDCl3) delta 7.92 (d, 1H), 8.58 (d, 1H).
2 Example 2:
Pyridine-3,5-disulfonic acid is made from 3,5-dichloro-pyridine which is transformed into 3,5-dichloro-pyridine-N-oxide with H2O2. This compound is treated at 135°C in an autoclave with an excess of Na2SC>3, resulting in the sodium salt of pyridine-3,5-disulfonic acid-N-oxide which is reduced by NaBH4 to yield the sodium salt of pyridine-3,5-disulfonic acid. The disalt is alkylated with methyl methanesulfonate to yield sodium [3,5-disulfonato-1 -methyl-pyridinium].
With 2,3-dimethyl-2,3-butane diol; bis(N,N-dimethylformamide)dichloridodioxidomolybdenum(VI) In N,N-dimethyl acetamide at 130℃; Microwave irradiation; Sealed tube; Green chemistry; chemoselective reaction;
With lithium tert-butoxide In dimethyl sulfoxide at 40℃; for 2h; Inert atmosphere; regioselective reaction;
4.4. General procedure for C-H fluoromethylation of heteroaryl N-oxides
General procedure: A mixture of heteroaryl N-oxide (0.4 mmol), [Ph3PCFH2]I (337.6 mg, 0.8 mmol), t-BuOLi (96.0 mg, 1.2 mmol) was added in a 10 mL Schlenk tube under N2 atmosphere, and then DMSO (4.0 mL) was added. The mixture was stirred at 40 °C for 2 h. After the reaction was complete, water was added. The resulting mixture was extracted with DCM for four times. The organic layer was washed with brine, dried over Na2SO4, filtered and removed under reduced pressure. The residue was purified by silica gel column chromatography to give the desired product (2a-2p).
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