JPH072775A - Production of substituted phenylpyridine - Google Patents

Abstract

PURPOSE:To produce a substituted phenylpyridine in a short process. CONSTITUTION:A halopyridine is reacted with 4-bromo-3-nitrophenetole in the presence of copper by using tetrakis(triphenylphosphine)palladium or palladium chloride catalyst in DMF or DMSO.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel process for producing substituted phenylpyridines. The object compound of the present invention is a compound useful as an intermediate for the production of pharmaceuticals, agricultural chemicals, liquid crystals and the like.

[0002]

Substituted phenylpyridines such as 3- (4-
Ethoxy-2-nitrophenyl) pyridine can be produced by converting diethyl- (3-pyridyl) borane into 4-bromo-
A method of reacting 3-nitrophenol in the presence of a palladium catalyst is known. However, this method has the problems that the raw materials and the catalyst are expensive, and that the catalyst must be handled carefully under a nitrogen or argon stream, and that the conditions greatly affect the yield. It is difficult to apply.

[0003]

SUMMARY OF THE INVENTION The present invention is to provide a method for producing a substituted phenylpyridine in a short step and in a high yield.

[0004]

Means for Solving the Problems As a result of various studies on the method for producing a substituted phenylpyridine, the present inventors have found a method capable of producing a target compound in an extremely high yield as compared with known methods, and completed the present invention. did.

The present invention involves reacting a halopyridine with 4-bromo-3-nitrophenetol in dimethylformamide or dimethylsulfoxide using a tetrakis (triphenylphosphine) palladium or palladium chloride catalyst in the presence of copper. And a method for producing a substituted phenylpyridine.

As the halopyridine which is the starting material of the present invention, 2-, 3- or 4-bromopyridine, 2-, 3-
Alternatively, 4-iodopyridine or the like is used. As the solvent, a mixture of dimethylformamide and dimethylsulfoxide may be used, or a mixture of dimethylformamide and / or dimethylsulfoxide and another solvent may be used. When iodopyridine is used as the halopyridine, it is preferable to use palladium chloride as the catalyst and dimethyl sulfoxide as the solvent. When bromopyridine is used, it is preferable to use tetrakis (triphenylphosphine) palladium as a catalyst and dimethylformamide as a solvent.

In carrying out the present invention, halopyridine and 4-bromo-3-nitrophenetol as starting materials are dissolved in the above solvent, copper and a catalyst are added to this solution, and then an inert gas atmosphere is added. Lower to react by heating.

The amount of 4-bromo-3-nitrophenol used is 1 to 3 mol, preferably 1.5 to 2.5 mol, per 1 mol of halopyridine. As the copper, copper powder, copper foil, copper wire or the like is used. The amount of copper used is 0.1 to 30 mol, preferably 1 to 10 mol, per 1 mol of halopyridine.
It is a mole. The amount of the catalyst used is 0.001 to 1 mol, preferably 0.01 to 0.5 mol, per 1 mol of halopyridine. For example, nitrogen gas is used as the inert gas. The heating temperature is 80 to 160 ° C., preferably 90 to 14
It is 0 ° C. The reaction is usually completed in 1 to 5 hours. The desired product can be isolated and purified by a conventional method.

[0009]

【Example】

Example 1. Synthesis of 3- (4-ethoxy-2-nitrophenyl) pyridine 700 mg (3.41 mmol) of 3-iodopyridine and 1.68 g (6.
82 mmol) in DMSO (10 ml), copper powder 8
70 mg (13.69 mmol) and Pd Cl ₂ 12 mg
(0.068 mmol) was added, and then under a nitrogen atmosphere, 1
The mixture was heated and stirred at 00 ° C for 2.5 hours. 10% in reaction mixture
Aqueous ammonia and toluene were added, the mixture was stirred, and the insoluble material was filtered. After separating the filtrate, the aqueous layer was further extracted with toluene, and the extract was washed with saturated brine. Then 2N-H
It was back-extracted with Cl, washed with toluene, and then made alkaline with NaOH. The aqueous layer was extracted with toluene, washed with saturated brine, and dried over anhydrous Na ₂ SO ₄ . The solvent was evaporated and the obtained residue was separated and purified by silica gel column chromatography to give the title compound (750 mg, 89.9%) as pale-yellow crystals with a melting point of 72 to 73 ° C.

Embodiment 2. Synthesis of 3- (4-ethoxy-2-nitrophenyl) pyridine 3-iodopyridine hydrochloride 824 mg (3.41 mmo)
l) and 4-bromo-3-nitrophenol 1.68 g
DMSO (4 ml) solution of (6.82 mmol), copper powder 868 mg (13.64 mmol) and PdCl ₂ 12m
After adding g (0.068 mmol), under nitrogen atmosphere 1
The mixture was heated and stirred at 00 ° C for 2.5 hours. Thereafter, post-treatment was carried out in the same manner as in Example 1 to give 696 mg (8
3.5%) was obtained. IR (KBr): 3059, 1625, 1525, 13
44, 1273, 1228, 1040, 870, 80
^{6,712cm -1 1 H-NMR (CDCl} 3) δ: 1.48 (3H, t,
_{J = 6.8Hz, C H 3)} , 4.14 (2H, q, J =
6.8 Hz, C H ₂ CH ₃ ), 7.19 (1 H, dd,
_{J = 8.7,2.9Hz, Ar- H 5)} , 7.31 (1
H, d, J = 8.7Hz, Ar- H 6), 7.30-
7.36 (1H, m, Py- H 5), 7.48 (1H,
d, J = 2.9Hz, Ar- H 3), 7.60 (1H,
dt, J = 7.8,2.0Hz, Py- H 4), 8.5
6 (1H, d, J = 2.0Hz, Py- H 2), 8.6
2 (1H, dd, J = 4.6, 2.0 Hz, Py-
H ₆ ). MS m / z: 244 (M ⁺ ), 199, 186, 17
0.

Embodiment 3. 2- to (4-ethoxy-2-nitrophenyl) pyridine 2-bromopyridine and 4-bromo-3-nitro-off energy Torr DMF solution, copper powder and _{(Ph 3 P) 4 Pd (} O)
After adding, the mixture was heated and stirred at 130 ° C for 3 hours under a nitrogen atmosphere. Then, the post-treatment was carried out in the same manner as in Example 1 to obtain the title compound as a pale yellow oil. Yield 54.3%.

IR (liq.): 2972, 1617,
1530, 1464, 1360, 1283, 1227,
1018,785 cm ^-1 . ¹ H-NMR (CDCl ₃ ) δ: 1.46 (3 H, t,
J = 6.8 Hz, CH ₃ ), 4.12 (2H, q, J =
_{6.8Hz, CH 2 CH 3),} 7.15 (1H, dd,
_{J = 8.7,2.4Hz, Ar- H 5)} , 7.26 (1
H, ddd, J = 7.8, 4.9, 1.4 Hz, Py-
H ₅ ), 7.37 (1H, d, J = 2.4 Hz, Ar−
_{H 3), 7.41 (1H,} d, J = 7.8Hz, Py-
H ₃ ), 7.52 (1H, d, J = 8.7 Hz, Ar−
H ₆ ), 7.75 (1H, dt, J = 7.8, 1.9H
_{z, Py- H 4), 8.61} (1H, br.d, J =
4.9Hz, Py- H _6).

Embodiment 4. Synthesis of 4- (4-ethoxy-2-nitrophenyl) pyridine When 4-bromopyridine is used instead of 2-bromopyridine, and otherwise the same as in Example 3, when heated and stirred at 130 ° C. for 2 hours, the melting point is 75- The title compound was obtained as pale yellow crystals at 77 ° C. Yield 44.0%.

IR (KBr): 3040,2980,1
616, 1600, 1533, 1355, 1269, 1
236, 1041, 815 cm ^-1 . ¹ H-NMR (CDCl ₃ ) δ: 1.48 (3H, t,
_{J = 6.8Hz, C H 3)} , 4.14 (2H, q, J =
_{6.8Hz, C H 2 CH 3)} , 7.16-7.23 (3
_{H, m, Ar- H 5,} Py- H 3 and- H 5), 7.
31 (1H, d, J = 8.3Hz, Ar- H 6), 7.
44 (1H, d, J = 2.4Hz, Ar- H 3), 8.
64 (2H, d, J = 4.9 Hz, Py− H ₂ and−
H ₆ ).

 ─────────────────────────────────────────────────── ─── Continuation of the front page (72) Inventor Yamaguchi ▲ Taka ▼ 7-32, Okayama-cho, Urawa-shi, Saitama Prefecture (72) Tomio Ota 4-41 Unoki, Sayama-shi, Saitama Prefecture

Claims (1)

[Claims] 1. Reacting a halopyridine with 4-bromo-3-nitrophenetol in the presence of copper using tetrakis (triphenylphosphine) palladium or palladium chloride catalyst in dimethylformamide or dimethylsulfoxide. A method for producing a substituted phenylpyridine, which is characterized.