JPH0475228B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel method for producing bipyridine derivatives.

More specifically, the present invention relates to a method for producing bipyridine derivatives, which is characterized by reacting a pyridyl sulfoxide having a substituent with a Grignard reagent.

Bipyridine derivatives can be used as chelating agents and
It is useful as a variety of intermediates for agricultural chemicals, dyes, detergents, pharmaceuticals, etc.

Generally, as a method for synthesizing bipyridine, for example, in the case of 2,2'-bipyridine, pyridine is mixed in a sealed tube,
Methods such as heating with anhydrous ferric chloride and refluxing pyridine in the presence of a Raney-nickel catalyst made by a special method are known. However, all of these methods require a long time for reaction, have low yields, and are complicated to operate, so they are not necessarily satisfactory as industrial production methods. In addition, all of these methods require harsh reaction conditions, so when trying to synthesize bipyridine with a substituent from pyridine with a substituent using these methods, the reality is that the target product is almost never obtained. It was hot.

The present inventors have conducted intensive research on a new method for producing substituted bipyridines, and as a result of their extensive research, they have discovered that 2,2'-
I thought that the method for producing bipyridine could also be used for producing substituted bipyridines, and when I carried out this method, I found that it was very easy and had a good yield.
The present invention was completed by discovering that the desired substituted bipyridines can be obtained.

That is, the present invention has the following general formula: (In the formula, R ¹ represents an alkyl group, an aryl group, an alkyl-substituted aryl group, an alkoxy-substituted aryl group, and Y ¹ to ^{Y 4} each represent hydrogen, an alkyl group, an aryl group, an aralkyl group, an alkoxy group,
Indicates a thioalkoxy group, an amino group, a cyano group, a halogen group, or an alicyclic or aromatic ring formed by bonding any two adjacent groups. however,
At least one of Y ¹ to ^{Y 4} is not hydrogen. ) and a pyridine derivative represented by the general formula R ² MgX [ ] (wherein R ² represents an alkyl group, an aryl group, an alkyl-substituted aryl group, or an alkoxy-substituted aryl group, and X represents a halogen). The general formula is characterized by reacting with a Grignard reagent (In the formula, Y ¹ to ^{Y 4} are the same as above.) This is a novel method for producing a bipyridine derivative represented by the following formula.

In the present invention, even if the pyridine ring has a substituent such as an alkyl group, an alkoxy group, a thioalkoxy group, an amino group, a cyano group, or a halogen group, it is not affected by the Grignard reagent and the substitution Bipyridine derivatives can be synthesized in good yield while leaving the groups intact.

That is, even if a substituent such as a halogen is attached to a pyridyl sulfoxide having a substituent, Grignard exchange between the substituent and the Grignard reagent does not occur, and an alkyl group such as a methyl group does not act as a substituent. Even if it exists as a substituent, bipyridine having the desired substituent group can be obtained in good yield without any proton abstraction reaction caused by the Grignard reagent. Generally, in such a cyclic compound, whether there is a substituent or not,
It is well known that the reactivity is not necessarily the same, and reactions that are possible in the absence of a substituent often do not proceed favorably due to the influence of the substituent. As mentioned above, despite the presence of a substituent such as a halogen, the reaction proceeds in the same way as when no other substituent is present, and the desired substituted bipyridines can be obtained in good yield. is completely surprising.

Used in the present invention, represented by the general formula []
In the bipyridine derivative, R ¹ is, for example,
Alkyl groups such as methyl, ethyl and propyl groups, aryl groups such as phenyl and naphthyl groups, alkyl-substituted aryl groups substituted with methyl, ethyl and propyl groups, methoxy groups, ethoxy groups, etc. and alkoxy-substituted aryl groups. In addition, ^Y1 to ^Y4 are, for example, hydrogen, alkyl groups such as methyl, ethyl, and propyl groups, aryl groups such as phenyl and naphthyl groups, aralkyl groups such as benzyl and phenethyl groups, and methoxy groups. , alkoxy groups such as ethoxy groups,
Thioalkoxy groups such as thiomethoxy group and thioethoxy group, halogen groups such as chlorine, bromine, and iodine,
_NH2 group, and N-monoalkylamino groups such as N-methylamino group and N-ethylamino group, N,N
- N,N-dialkylamino groups such as dimethylamino group, N,N-diethylamino group, N-arylamino group such as N-phenylamino group, N,N-diarylamino group such as N,N-diphenylamino group, N -Methyl-N'-phenylamino group, etc.
-alkyl-N'-arylamino group, cyano group,
Or an alicyclic ring or an aromatic ring formed by bonding any two adjacent groups.

The Grignard reagent used in the present invention includes:
Examples include those represented by the general formula R ² MgX,
Examples of R ² include alkyl groups such as methyl, ethyl, and propyl groups, aryl groups such as phenyl and naphthyl groups, alkyl-substituted aryl groups substituted with methyl groups and ethyl groups, methoxy groups, ethoxy groups, etc. Examples of X include halogens such as chlorine, bromine, and iodine.

The reaction is usually carried out at a temperature of 0 to 30°C, preferably 15 to 25°C.

Pyridyl sulfoxides having substituents used in the present invention can generally be easily obtained as follows.

For example, 2-chloro-6-methylsulfinylpyridine can be obtained as follows.

That is, 2,6-dichloropyridine and methyl mercaptan are mixed in an organic solvent such as benzene,
The reaction is carried out by heating and stirring in the presence of a phase transfer catalyst such as tetra-n-butyl-ammonium bromide. After the reaction, the organic layer is separated, washed with water, dried, and then the solvent is distilled off to quantitatively obtain 2-chloro-6-methylfluphenylpyridine. Next, by oxidizing this with an oxidizing agent such as hydrogen peroxide, the desired 2-chloro-6-methylsulfinylpyridine can be obtained quantitatively.

The present invention can be easily implemented, for example, as follows.

For example, under a nitrogen atmosphere, in an aprotic solvent in which pyridyl sulfoxide with a substituent is dissolved,
At room temperature or under cooling, an aprotic solvent solution containing 0.5 to 1 mole, preferably 0.5 to 0.6 mole of Grignard reagent is added and stirred well. The color of the reaction solution immediately changed from red to yellow,
A precipitate comes out. After stirring for 15 minutes to several hours, water is added to the reaction mixture, and the aqueous layer is extracted several times with a solvent such as dichloromethane. This organic layer is washed with water, dried with a drying agent such as Na ₂ SO ₄ , and if necessary, the solvent is distilled off under reduced pressure to obtain the desired bipyridine derivative. If necessary, it may be purified and isolated by column chromatography or the like.

In this reaction, in addition to the bipyridine derivative, sulfoxide and thiosulfinate are produced as by-products. Therefore, when R ¹ in the formula [] and R ² in the formula [] are a methyl group or an ethyl group, the by-products dimethyl sulfoxide and ethyl methyl sulfoxide are easily soluble in water, so the reaction is difficult. This is preferable because it is easy to process after completion.

The solvent used in the present invention is usually an aprotic solvent, such as benzene, toluene,
Examples include hydrocarbons such as xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, and anisole, and glymes such as ethylene glycol diethyl ether and diethylene glycol dimethyl ether. These solvents can be used alone or in combination. It may also be used as

The present invention provides that a desired bipyridine derivative can be obtained extremely easily and in high yield by reacting a pyridyl sulfoxide having a substituent with a Grignard reagent under mild conditions, and a wide range of bipyridine derivatives can be obtained. This is an extremely excellent manufacturing method.

As described above, the present invention provides a chelating agent,
The present invention provides a method for producing bipyridine derivatives, which are useful as agrochemicals, medicines, dyes, surfactants, and various other synthetic intermediates, very easily and with high yield, and thus makes a huge contribution to this industry.

The present invention will be described below with reference to Reference Examples and Examples, but the present invention is not limited thereto.

Reference example 1 2,6-dichloropyridine 50g (0.338mo)
and sodium methyl mercaptan (15% aqueous solution)
Mix 237g (0.508mo) with 150ml of benzene,
To this was added 3 g (0.0093 mo) of tetra-n-butylammonium bromide, and the mixture was refluxed for 6 hours with vigorous stirring. After the reaction is completed, the organic layer is separated, washed thoroughly with water, dried over anhydrous magnesium sulfate, and then the solvent is distilled off under reduced pressure. By distilling the residue under reduced pressure, 52.9 g of colorless and transparent 2-chloro-6-methylsulfenylpyridine was obtained.
(yield 98%).

bp: 105-107℃/14mmHg.

IR (neat): ν=2940, 1570, 1415, 1160, 795
cm ^-1 .

NMR (CC ₄ ): δ=2.47 (s, CH ₃ , 3H),
6.60-7.37ppm (m, pyrH, 3H).

Elemental analysis: C ₆ H ₆ NSC Actual value (%): C 45.2; H 3.8; N
9.0 Calculated value (%): C 45.1; H 3.8; N
8.8 Similarly, the following sulfenylpyridines are obtained.

2-bromo-6-methylsulfenylpyridine Yield 97%.

bp 128-132℃/16mmHg.

IR (neat): ν=2920, 1560, 1405, 1150, 770
cm ^-1 .

NMR (CDC ₃ ): δ = 2.50 (s, CH ₃ , 3H),
6.78-7.53ppm (m, pyrH, 3H).

Elemental analysis: C ₆ H ₆ NSBr Actual value (%): C 35.7; H 24.9; N
6.95 Calculated value (%): C 35.3; H 3.0; N
6.95 5-chloro-2-methylsulfenylpyridine Yield 92% bp 115-117°C/24mmHg.

IR (neat): ν=2930, 1560, 1410, 1150, 775
cm ^-1 .

NMR (CDC ₃ ): δ=2.54 (s, CH ₃ , 3H),
7.1 (dd, 3-pyrH, 1H, J=10Hz, J=1Hz),
7.45 (dd, 4-pyrH, 1H, J=9Hz, J=3
Hz), 8.38ppm (dd, 6-pyrH, 1H, J=3Hz,
J=1Hz).

Elemental analysis: C ₆ H ₆ NSC Actual value (%): C 44.90; H 3.76; N
8.74 Calculated value (%): C 45.14; H 3.78; N
8.77 3,5-Dichloro-2-methylsulfenylpyridine Yield 95% mp 63-64°C.

NMR (CDC ₃ ): δ=2.54 (s, CH ₃ , 3H),
7.6 (d, 4-pyrH, 1H, J=2Hz), 8.33ppm
(d, 6-pyrH, 1H, J=2Hz).

Elemental analysis: C ₆ H ₅ NSC ₂ Actual value (%): C 37.02; H 2.58; N
7.11 Calculated value (%): C 37.13; H 2.59; N
7.21 3-amino-2-ethylsulfenylpyridine bp 151℃/20mmHg Reference example 2 13g of sodium metal in 200ml of ethanol
(0.505 mo) was dissolved in this under a nitrogen atmosphere.
2-chloro-6-methylsulfenylpyridine 20
g (0.125 mo) is added dropwise. After refluxing the reaction mixture for 13 hours, the solvent is distilled off under reduced pressure. Add water to the residue and extract three times with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was distilled under reduced pressure to obtain 14.8 g (yield: 70%) of the desired 2-ethoxy-6-methylsulfenylpyridine.

bp 118-124℃/26mmHg.

IR (neat): ν=2980, 1565, 1435, 1290, 785
cm ^-1 .

NMR (CC ₄ ): δ = 1.49 (t, OCH ₂ CH ₃ ,
3H, J=8Hz), 2.60 (s, SCH ₃ , 3H), 4.45
(q, OC H ₂ CH ₃ , 2H, J = 8Hz), 6.33 (d, 3
-pyrH, 1H, J=8Hz), 6.69(d, 5-pyrH,
1H, J = 8Hz), 7.34ppm (t, 4-pyrH, 1H,
J=8Hz).

Reference example 3 3.5g of metallic sodium in 200ml of ethanol
(0.150mol) was dissolved in this under a nitrogen atmosphere.
Sodium methyl mercaptan (15% aqueous solution) 70.1
g (0.150 mol) and stirred for 10 minutes.
-chloro-6-methylsulfenylpyridine
Add 20g (0.120mol) dropwise. Reaction mixture 24
After refluxing for an hour, water is added and extracted three times with benzene. The organic layers were combined, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was distilled under reduced pressure to obtain 17.8 g (yield: 83%) of the desired 2,6-bis(methylsulfenyl)pyridine.

bp 95℃/3mmHg.

NMR (CC ₄ ): δ=2.80 (s, CH ₃ , 6H),
6.91-7.53ppm (m, 3, 4, 5, -pyrH, 3H).

Elemental analysis: C ₇ H ₉ NS ₂ Actual value (%): C 49.29; H 5.24; N
8.41 Calculated value (%): C 49.08; H 5.29; N
8.17 Reference example 4 Metallic sodium in 20ml of methanol 1.6
To this solution, 5 ml of ethanethiol was added dropwise under a nitrogen atmosphere, and after stirring for 10 minutes, 9.8 g of 2-bromo-6-methylpyridine was added dropwise.
After heating the reaction mixture to reflux for 48 hours, water was added and
Extract with benzene three times. The organic layers were combined, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was distilled under reduced pressure to obtain 4.5 g of the desired 2-ethylsulfenyl-6-methylpyridine (yield:
52%).

bp 107℃/15mmHg.

NMR ( _CDC3 ): _δ =1.37(t, _-CH2CH3 ,
3H, J=7Hz), 2.49(s, 6-pyr- _CH3 ,
3H), 3.16 (q, -C H ₂ CH ₃ , 2H, J = 7Hz),
7.50-6.75ppm (m, pyrH, 3H).

Elemental analysis: C ₈ H ₁₁ NS Actual value (%): C 62.90; H 7.26; N
9.20 Calculated value (%): C 62.70; H 7.23; N
9.14 Similarly, the following sulfenylpyridines are obtained.

2-ethylsulfenyl-4-methylpyridine Yield 88% bp 117-119/21mmHg NMR ( _CDC3 ): δ= _1.36 (t, _-CH2CH3 ,
3H, J=7Hz), 2.25(s, 4-pyr- _CH3 ,
3H), 3.16 (q, -C H ₂ CH ₃ , 2H, J = 7Hz),
6.78 (d, 5-pyrH, 1H, J=5Hz), 6.97 (s,
3-pyrH, 1H), 8.23ppm (d,6-pyrH, 1H,
J=5Hz).

Reference example 5 2-chloro-6-methylsulfenylpyridine
Dissolve 10g (0.063mol) in 100ml of acetic acid,
While cooling to 15℃, add 9.2 g of 30% H ₂ O ₂ aqueous solution to this.
(0.082 mo) was added dropwise and stirred at room temperature for 12 hours.
After the reaction is complete, saturated aqueous ammonia is added to make the mixture slightly alkaline, followed by extraction three times with dichloromethane.
After combining the organic layers and drying with anhydrous magnesium sulfate,
The solvent was distilled off under reduced pressure. The obtained white solid was recrystallized from benzene-hexane to obtain the desired 2-chloro-6-methylsulfinylpyridine.
Obtain 10.45 g (95% yield).

mp 66.0~66.5℃ IR (KBr): ν=3080, 1555, 1410, 1120,
1050 (S→O), 810, 775 cm ^-1 .

NMR (CDC ₃ ): δ 2.74 (s, CH ₃ , 3H),
7.11-7.80ppm (m, pyrH, 3H).

Elemental analysis: C ₆ H ₆ NOSC Actual value (%): C 40.98; H 3.45; N
7.98 Calculated value (%): C 41.03; H 3.44; N
7.97 Similarly, the following sulfinylpyridines are obtained.

2-Bromo-6-methylsulfinylpyridine Yield 90% mp 76.5-77.0℃.

NMR (CC ₄ ): δ=2.74 (s, SCH ₃ , 3H),
7.25-7.86ppm (m, pyrH, 3H).

Elemental analysis: C ₆ H ₆ BrNOS Actual value (%): C 32.90; H 2.67; N
6.38 Calculated value (%): C 32.74; H 2.74; N
6.36 5-chloro-2-methylsulfinylpyridine Yield 65% mp 52-53°C.

NMR (CDC ₃ ): δ = 2.85 (s, CH ₃ , 3H),
7.98~7.94 (m, 3, 4-pyrH, 2H), 8.61~
8.56ppm (m, 6-pyrH, 1H).

3,5-Dichloro-2-methylsulfinylpyridine Yield 71% mp 95-96°C.

NMR (CDC ₃ ): δ = 2.89 (s, CH ₃ , 3H),
7.82 (d, 4-pyrH, 1H, J=2Hz), 8.69ppm
(d, 6-pyrH, 1H, J=2Hz).

2-Ethoxy-6-methylsulfinylpyridine Yield 52% mp 33-35° _C NMR ( _CDC3 ): δ=1.39 (t, _OCH2CH3 ,
3H, J=7Hz), 2.83(s, S(O)CH ₃ , 3H),
4.36 (q, OC H ₂ CH ₃ , 2H, J = 7Hz), 6.77 (dd,
3-pyrH, 1H, J=8Hz, J=2Hz), 7.48~
7.29ppm (m, 4,5-pyrH, 2H).

2-Methylsulfenyl-6-methylsulfinylpyridine Yield 60% bp 134-137°C/4mmHg.

NMR (CDC ₃ ): δ=2.50 (s, SCH ₃ , 3H),
2.80 (s, S(O)CH ₃ , 3H), 7.01-7.23 (m, 5
-pyrH, 1H), 7.47-7.87ppm (m, 3, 4-
pyrH, 2H).

Elemental analysis: C ₇ H ₉ NS ₂ O Actual value (%): C 44.85; H 4.88; N
7.59 Calculated value (%): C 44.89; H 4.84; N
7.47 2-ethylsulfinyl-4-methylpyridine Yield 66% bp 137-139°C/6mmHg.

NMR ( _CDC3 ): _δ =1.20(t, _-CH2CH3 ,
3H, J=7Hz), 2.47(s, 4-pyr- _CH3 ,
3H), 3.28 _~ 2.47 (m, _-CH2CH3,2H ), 7.22~
7.10 (m, 5-pyrH, 1H), 7.83-7.78 (m, 3-
pyrH, 1H), 8.47 ppm (d,6-pyrH, 1H).

2-ethylsulfinyl-6-methylpyridine Yield 77% bp 103-104℃/4mmHg.

NMR ( _CDC3 ): _δ =1.21(t, _-CH2CH3 ,
3H, J=7Hz), 2.59(s, 6-pyr- _CH3 ,
3H), 3.38 _~ 2.63 (m, _-CH2CH3,2H ), 7.35~
7.14 (m, 5-pyrH, 1H), 7.85-7.76ppm (m,
3,4-pyrH,2H).

Reference example 6 2-chloro-6-methylsulfinylpyridine 2g (0.011mo) and piperidine 3.62g
(0.043 mo) was added and refluxed at 120°C for 1 hour. After the reaction, water was added and extracted with chloroform.
After washing with water and drying, this was purified by column chromatography (silica gel, chloroform) and the solvent was distilled off to obtain 1.8 g of the desired 2-methylsulfinyl-6-piperidinopyridine (yield:
58%).

NMR (CDC ₃ ): δ=1.65(m, (CH ₂ ) ₃ ,
6H), 2.81 (s, CH ₃ , 3H), 3.55 (m, CH ₂ −N
-C H ₂ , 4H), 6.60-7.77ppm (m, 3, 4, 5
−pyrH, 3H).

Example 1 2-chloro-6-methylsulfinylpyridine
9.42 g (0.0536 mo) of diethyl ether (Et ₂
O) Dissolve in 200 ml, add 32 ml of 1M C ₂ H ₅ MgBr/Et ₂ O solution while stirring under cooling in a nitrogen atmosphere, then return to room temperature and continue stirring. The color of the reaction solution changes from red to yellow, and a precipitate begins to separate out. After stirring for 1 hour, water is added to the reaction mixture and extracted three times with dichloromethane. The organic layers were combined, washed with water, and dried over anhydrous sodium sulfate.
By distilling off the solvent under reduced pressure, the desired 6,
3.32 g of 6'-dichloro-2,2'-bipyridine (yield
55%).

mp: 216 ~ 217℃ (lit. 218 ~ 219℃) NMR (CDC ₃ ): δ = 7.35 (dd, 5, 5'-
pyrH, 2H, J=8Hz, J=1Hz), 7.77(t,
4,4′-pyrH,2H,J=7Hz), 8.36ppm(dd,
3,3'-pyrH, 2H, J=7Hz, J=1Hz).

Example 2 In Example 1, 2-bromo-
Using 11.80g of 6-methylsulfinylpyridine,
The reaction and treatment were carried out in the same manner as in Example 1 to obtain 4.21 g of 6,6'-dibromo-2,2'-bipyridine (yield 50%).
get.

mp: 228-229℃ (lit. 226-227℃) NMR (CDC ₃ ): δ = 7.48 (dd, 5, 5'-
pyrH, 2H, J=8Hz, J=2Hz), 7.68(t,
4,4′-pyrH,2H,J=8Hz), 8.38ppm(dd,
3,3′-pyrH,2H,J=7Hz,J=2Hz).

Example 3 In Example 1, 2-chloro-6-methylsulfinylpyridine was replaced with 9.42 g of 2-chloro-6-methylsulfinylpyridine.
Using 10.04 g, the reaction and treatment were carried out in the same manner as in Example 1 to obtain 6,6'-dimethylthio-2,2'-bipyridine.
Obtain 4.06 g (yield 61%).

mp: 130-131℃.

NMR (CDC ₃ ): δ = 2.67 (s, SCH ₃ , 6H),
7.17 (dd, 5, 5'-pyrH, 2H, J=8Hz, J=1
Hz), 7.61 (t, 4, 4'-pyrH, 2H, J = 8 Hz),
8.17ppm (dd, 3, 3'-pyrH, 2H, J = 7Hz, J
= 1Hz).

Elemental analysis: C ₁₂ H ₁₂ N ₂ S ₂ Actual value (%): C 58.03; H 4.87; N
11.27 Calculated value (%): C 57.78; H 4.48; N
11.14 Example 4 In Example 1, 12.02 g of 2-methylsulfinyl-6-piperidinopyridine was used instead of 9.42 g of 2-chloro-6-methylsulfinylpyridine, and the same procedure as Example 1 was carried out. React and process in the same way 6.
6′-dipiperidino-2,2′-bipyridine 3.80g
(yield 44%).

mp: 182-185℃.

NMR (CDC ₃ ): δ = 1.50 to 1.82 (m, CH ₂ ,
12H), 3.45-3.80 (m, CH2 _- N'- _CH2 , 8H),
6.55~6.80 (m, 5, 5′-pyrH, 2H), 7.35~
7.82ppm (m, 3, 3', 4, 4'-pyrH, 4H).

Example 5 In Example 1, 9.93 g of 2-ethoxy-6-methylsulfinylpyridine was used in place of 9.42 g of 2-chloro-6-methylsulfinylpyridine, and the reaction was carried out in the same manner as in Example 1. and processed to give 6,6'-
Diethoxy-2,2'-bipyridine 1.90g (29
%).

mp 78-79℃.

NMR (CDC ₃ ): δ = 1.43 (t, CH ₃ , 6H, J
= 7Hz), 4.51 (q, CH ₂ , 4H, J = 7Hz), 6.71
(dd, 5, 5'-pyrH, 2H, J=7Hz, J=2
Hz), 7.54 (dd, 4, 4'-pyrH, 2H, J=7Hz,
J = 7Hz), 7.97ppm (dd, 3, 3'-pyrH, 2H,
J=7Hz, J=2Hz).

Example 6 In Example 1, 9.07 g of 2-ethylsulfinyl-6-methylpyridine was used in place of 9.42 g of 2-chloro-6-methylsulfinylpyridine, and the reaction was carried out in the same manner as in Example 1. and processed into 6,6'-
Dimethyl-2,2'-bipyridine 2.81g (57%)
get.

mp 89-90℃.

NMR (CDC ₃ ): δ=2.62 (s, CH ₃ , 6H),
7.14 (d, 5, 5'-pyrH, 2H, J = 8Hz), 7.54
(t, 4, 4'-pyrH, 2H, J = 8Hz), 8.20ppm
(d,3,3′-pyrH,2H,J=8Hz).

Example 7 In Example 1, 9.42 g of 2-chloro-6-methylsulfinylpyridine was replaced with 5-chloro-
Using 9.42g of 2-methylsulfinylpyridine,
The reaction and treatment were carried out in the same manner as in Example 1 to obtain 2.41 g (40%) of 5,5'-dichloro-2,2'-bipyridine.

mp200~202℃.

NMR (CDC ₃ ): δ = 7.77 (dd, 3, 3'-
pyrH, 2H, J=9Hz, J=3Hz), 8.35(dd,
4,4'-pyrH,2H, J=9Hz, J=1Hz), 8.63
~8.59ppm (m,6,6′-pyrH,2H).

Example 8 In Example 1, 9.05 g of 2-ethylsulfinyl-4-methylpyridine was used instead of 9.42 g of 2-chloro-6-methylsulfinylpyridine,
React and work up as in Example 1 to obtain 2.46 g (50%) of 4,4'-dimethyl-2,2'-bipyridine.

mp145~152℃.

NMR (CDC ₃ ): δ = 2.41 (s, CH ₃ , 6H),
7.12 (d, 5, 5'-pyrH, 2H, J = 5Hz), 8.24
(s, 3, 3′-pyrH, 2H), 8.43 ppm (d, 6,
6'-pyrH, 2H, J = 5Hz).

Example 9 In Example 1, 9.42 g of 2-chloro-6-methylsulfinylpyridine was replaced with 11.26 g of 3,5-dichloro-2-methylsulfinylpyridine.
was reacted and treated in the same manner as in Example 1 to obtain 3,
3',5,5'-tetrachlor-2,2'-bipyridine
Obtain 4.10g (52%).

mp103~104℃.

NMR (CDC ₃ ): δ = 7.87 (d, 4, 4'-
pyrH, 2H, J = 2Hz), 8.60ppm (d, 6, 6'-
pyrH, 2H, J = 2Hz).

Example 10 4 g (0.0228 mo) of 2-chloro-6-methylsulfinylpyridine was dissolved in 80 ml of Et ₂ O, and 1M was added to the solution under cooling and stirring in a nitrogen atmosphere.
Add 12 ml of C ₆ H ₅ MgBr/Et ₂ O solution, then return to room temperature and continue stirring. The color of the reaction solution changes to red, and a precipitate begins to separate out. After stirring for 1 hour, water was added to the reaction mixture and extracted three times with dichloromethane. The organic layers were combined, washed with water, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. By purifying this material by column chromatography (activated alumina, benzene), 1.79 g of the desired 6,6'-dichloro-2,2'-bipyridine was obtained.
(yield 70%).

Example 11 In Example 10, as a Grignard reagent,
Instead of 12 ml of 1M C ₆ H ₅ MgBr/Et ₂ O solution, 1M
Using 12 ml of p-CH ₃ OC ₆ H ₄ MgBr/Et ₂ O solution,
The reaction and treatment were carried out in the same manner as in Example 10 to obtain 1.72 g of 6,6'-dichloro-2,2'-bipyridine. (Yield 67%) Example 12 In Example 10, as a Grignard reagent,
Instead of 12 ml of 1M C ₆ H ₅ MgBr/Et ₂ O solution,
_{6 . _ _}
1.67 g of 6'-dichloro-2,2'-bipyridine is obtained. (Yield 65%) Example 13 2-chloro-6-methylsulfinylpyridine
Dissolve 4.5 g (0.0256 mo) in 100 ml of Et ₂ O, and add 1M to this in a nitrogen atmosphere while cooling and stirring.
Add 13 ml of CH ₃ MgI/Et ₂ O solution of
Return to room temperature and continue stirring. The color of the reaction solution changes to white, and a precipitate begins to separate out. After stirring for 12 hours,
Water was added to the reaction mixture and treated in the same manner as in Example 1 to obtain the desired 6,6'-dichloro-2,2'-
0.69 g (yield 24%) of bipyridine is obtained.

Example 14 2-chloro-6-methylsulfinylpyridine
Dissolve 4.45g (0.0253mo) in 100ml of tetrahydrofuran (THF) and add to it in a nitrogen atmosphere.
1M C ₂ H ₅ MgBr/THF while stirring under cooling.
Add 13 ml of the solution, then return to room temperature and continue stirring. The color of the reaction solution changes to red, and a precipitate begins to separate out. After stirring for 12 hours, water was added to the reaction mixture and treated in the same manner as in Example 1 to obtain 0.94 g of the desired 6,6'-dichloro-2,2'-bipyridine.
(yield 33%).

Claims (1)

[Claims] 1. General formula (In the formula, R ¹ represents an alkyl group, an aryl group, an alkyl-substituted aryl group, an alkoxy-substituted aryl group, and Y ¹ to ^{Y 4} each represent hydrogen, an alkyl group, an aryl group, an aralkyl group, an alkoxy group,
It represents a thioalkoxy group, an amino group which may have a substituent, a cyano group, a halogen group, or an alicyclic or aromatic ring formed by bonding any two adjacent groups. However, at least one of Y ¹ to ^{Y 4} is not hydrogen. ) and a pyridine derivative represented by the general formula R ² MgX [ ] (wherein R ² represents an alkyl group, an aryl group, an alkyl-substituted aryl group, or an alkoxy-substituted aryl group, and X represents a halogen). The general formula is characterized by reacting with a Grignard reagent (In the formula, ^Y1 to ^Y4 are the same as above.) A method for producing a bipyridine derivative represented by the following.