JPS60188370A - Production of bipyridine derivative - Google Patents

Abstract

PURPOSE:To produce the titled compound useful as a chelating agent, easily in high yield, without being influenced with Grignard reagent, leaving the substituent groups as it is, under mild condition, by reacting a specific pyridine derivative with a Grignard reagent. CONSTITUTION:The objective compound of formula III is produced by reacting the pyridine derivative of formula I [R<1> is alkyl, (alkyl-substituted) aryl or alkoxy-substituted aryl; Y<1>-Y<4> are H, alkyl, aryl, aralkyl, alkoxy, thioalkoxy, amino, cyano, halogen, or adjacent two groups together form alicyclic or aromatic group; at least one of Y<1>-Y<4> is not H] with the Grignard reagent of formula II [R<2> is alkyl, (alkyl-substituted) aryl or alkoxy-substituted aryl; X is halogen] in an aprotic solvent in N2 atmosphere at 0-30 deg.C for 15min- several hours, and distilling out the solvent under reduced pressure. USE:A synthetic intermediate of agricultural chemicals, pharmaceuticals, dyes, surfactants, etc.

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 are still used as pesticides, pesticides, etc.
It is useful as a variety of intermediates for dyes, detergents, pharmaceuticals, etc.

Generally, as a method for synthesizing bipyridine, for example, 2.2'
- In the case of bipyridine, there are known methods such as heating pyridine with anhydrous ferric iron in a sealed tube, and refluxing pyridine in the presence of a Raney nickel catalyst prepared by a special method. However, these methods were not necessarily satisfactory as industrial production methods, such as requiring a long time for reaction, low yields, and complicated operations.

However, all of these methods require harsh reaction conditions, so when trying to synthesize bipyridine with a substituent from pyridine with a substituent, it is difficult to obtain the desired product. was the actual situation.

The present inventors have conducted intensive research on a new method for producing substituted bipyridines, and as a result, the present inventors have previously discovered that 2,2'-bipyridine can be produced from 2-pyridylmethylsulfoxide tophenylmagnesium bromide. We thought that the method for producing substituted bipyridines could also be used for producing substituted bipyridines, and when we carried out this process, we found that the desired substituted bipyridines could be obtained extremely easily and in good yields. completed.

That is, the present invention has the following formula:
-Y' is hydrogen, an alkyl group, an aryl group,
It represents an aralkyl group, an alkoxy group, a thioalkoxy group, an amino group, a cyano group, a )/logen group, or an alicyclic or aromatic ring formed by bonding any two adjacent groups. However, at least one of Yl to Y4 is not hydrogen. )
It is characterized by reacting a pyridine derivative represented by the following with a Grignard reagent represented by the general formula R'MgX [:II].

4- (wherein Y'' to Y'' are the same as above. Even if it has a substituent such as an amino group, a cyano group, or a rogene group, it is not affected by the Grignard reagent, and bipyridine derivatives with the substituent remaining can be synthesized in good yield.

In other words, even if pyridyl sulfoxides have a substituent such as norrogen, glycolation between this and the Grignard reagent does not occur, and pyridyl sulfoxides such as methyl groups do not undergo glycolysis. Even if an alkyl group is present as a substituent, bipyridine having the desired substituent can be obtained in good yield without any proton abstraction reaction using a Grignard reagent. In general, such cyclic compounds It is well known that the reactivity is not necessarily the same in the presence and absence of substituents, and that reactions that are possible in the absence of substituents are more convenient due to the influence of the substituted 5- group. It is a common occurrence that no progress is made. As mentioned above, despite the presence of a substituent such as norogen (7), the reaction proceeds in the same manner as when no other substituent is present, and the desired substituted bipyridine is produced in high yield. It is quite surprising that it is so well obtained.

In the pyridine derivative represented by the general formula [I] used in the present invention, R1 is, for example, an alkyl group such as a methyl group, an ethyl group, or a propyl group, an aryl group such as a phenyl group or a naphthyl group, or a methyl group. Examples include an alkyl-substituted aryl group substituted with an ethyl group, a propyl group, etc., and an alkoxy-substituted aryl group substituted with a methoxy group, an ethoxy group, etc. In addition, for Y1 to Y", for example,
Hydrogen, or alkyl groups such as methyl, ethyl, and propyl; aryl groups such as phenyl and naphthyl; aralkyl groups such as benzyl and phenethyl; alkoxy groups such as methoxy and ethoxy; group, N-monoalkylamino group such as N-ethylamino group, N,N-dialkylamino group such as N,N-dimethylamino group, N,N-diethylamino group, N-aryl such as N-phenylamino group Amino group, N,N-diarylamino group such as N,N-diphenylamino group, N
-N-alkyl- such as methyl-N'-phenylamino group
Examples include an N'-arylamino group, a cyano group, and an alicyclic or aromatic ring formed by bonding any two adjacent groups.

The Grignard reagent used in the present invention has the general formula
Examples of R2 include alkyl groups such as methyl, ethyl and propyl groups, aryl groups such as phenyl and naphthyl groups, and alkyl-substituted aryl groups substituted with methyl groups and ethyl groups. , an alkoxy-substituted aryl group substituted with a methoxy group, an ethoxy group, etc., and X is, for example, chlorine, bromine,
Examples include halogens such as 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 heated and stirred to react in an organic solvent such as benzene in the presence of a phase transfer catalyst such as tetra-butyl-ammonium puromite. After the reaction, the organic layer was separated, washed with water, dried, and the solvent was distilled off to obtain 2-chloro-
6-Methylsulfinylpyridine is obtained quantitatively. Then, by oxidizing this with an oxidizing agent such as hydrogen peroxide, the desired 2-chloro-6-methylsulfinylpyridine is obtained.The present invention can be easily carried out, for example, as follows.

For example, in a nitrogen atmosphere, in an aprotic solvent in which pyridyl sulfoxide having a substituent is dissolved, at room temperature or under cooling, 0.5 to 1 mole, preferably 0.5 to 0.6
Add an aprotic solvent solution containing twice the molar amount of Grignard reagent and stir well. The color of the reaction solution immediately changes from red to yellow, and a precipitate begins to separate out. After stirring for 15 minutes to several hours, water is added to the reaction mixture, and the water 1 is extracted several times with a solvent such as dichloromethane. This organic layer is washed with water, dried with a desiccant such as Na2SO4, 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 bipyridine derivatives, sulfoxide,
Thiosulfinate is produced as a by-product. Therefore, formula [I]
When R1 in the formula and R2 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.
This is preferable because it is easy to process after the reaction is completed.

The solvent used in the present invention is usually an aprotic solvent, such as hydrocarbons such as benzene, toluene, and 9-xylene, ethers such as diethyl ether, tetrahydrofuran, dioxane, and anisole,
Examples include noglymes such as ethylene glycol diethyl ether and diethylene glycol cimether ether,
These solvents may be used alone or in combination.

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. As described above, the present invention allows bipyridine derivatives, which are useful as chelating reagents, agricultural chemicals, pharmaceuticals, dyes, surfactants, and various other synthetic intermediates, to be produced extremely easily. In addition, it provides a method for manufacturing with high yield, making 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.

10- Reference example 1゜2,6-dichloropyridine 50g (0,338mot
) and sodium methylmercabutane (15% aqueous solution) 2
37 i (0,508mol) be/there 150m
To this, add tetra-n-butylammonium Ill? Id 39 (0,0093 mol) was added and the mixture was refluxed for 6 hours with vigorous stirring. After the reaction is complete,
The organic layer is separated, washed thoroughly with water, dried over anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. Distillation of the residue under reduced pressure yields a colorless and transparent 2-chloro-6
-Methylsulfenylpyridi 152.9g (yield 98%)
).

bp: 105-107°C/1.4 rranHg.

TR (neat) Niji = 2940, 1570, 14
]5゜1160.795Crn-1゜NMR (CC14): δ= 2.47 (s, (J
-T3. :H(), 6.60-7.37 Ppm (
m, pYrI (,3H).

Elemental analysis: C6H6N5Ct Actual value (3): C45,2; H3,8; N 9.0 Calculated value (a): C45,1;) (3,8; N 8.8 Similarly, the following sulfenyl Obtain pyridines.

Yield of 2-from-6-methylsulfenyl IJ) 97%.

bp], 28-132°C/16 mmHg.

IR (neat) Niji=2920.1560,140
5゜]1-50, 770c1n, -1゜NMR(C1)Ct, ): δ -2,50(s, C
H3, 3T-1), 6.78 to 7.53 ppm
(m, pyrT-1, 31-T).

Elemental analysis: Ce, 86 N S Br actual value 1%
e: C35,7; H2,94; N 6.95 calculated value n:
c 35.3; H3,0; N 6.955-chloro-2
-Methylsulfenylpyricine yield 92% bp], ], 5-117°O/24 mml-mm
1-T neat) Niji=2930. ] 560,14
10゜1150.775 -1゜N M R (CDCl2) 'δ= 2.54. (s
, Cl-13, 31-T), 7. ], (dd.

3-pYrIT, ]-J-T, J-=I Qllz
, J =], IIz), 7.45 Shiho (d d.

4-pyr((, IH, J=911z, J=3Hz)
, 8.38ppm (dd.

6-pyrl-T, LH, J=3Hz, J=11
Iz).

Elemental analysis C6H6N5ct Actual value n: c 44.90; I-T 3.76; N 8
．． 74 calculated value hook 'C45,14:FT 3.78;N
8,773.5-Dichloro-2-methylsulfenylpyridine Yield 95% mp 63-64°c.

NMR (CDCz3): δ = 2.54 (s, C
H3, 3H), 7.6 (d, 4 pyrH, IH
, J=2Hz), 8.33pprn (d, 6-
pyrI (, IH, J = 2Hz).

Elemental analysis: C6H3NSCt2 Actual value (if!'): ('37.02;H2,58;
N 7.11 Calculated value (To) C37,13: I-T 2.
59;N 7.213-amino-2-ethylsulfenylpyridi/bp '151°C/20 mrrtl-
1g Reference Example 2゜Metal sodium in 2 ooml of ethanol ]-3g (0
, 505mat) and added to this under a nitrogen atmosphere,
2-chloro-6-methylsulfenylpyridi20 jj
(0,125mat) was added dropwise. 1 of the reaction mixture
After refluxing for 3 hours, the solvent was distilled off under reduced pressure.

Add water to the residue and extract three times with dichloromethane. The organic layers were combined, dried over 1 mn of anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue was distilled under reduced pressure to obtain the desired 2-ethoxytoxy-6-methylsulfenylpyridine i4. s,
F (yield 7o%) is obtained.

bp 11.8-124°C/26 mmHg.

IR(neat): shi=2980.1565,1
435°1290.785C7n-1°NMR (CC14): δ-]-,4,9(t, 0C
H2CHs.

3 H, J = 8 fez), 2.60 (s,
5Ci (3, 3H), 4, 45 (q, occi
H3,2H, J=811z), 6.33(d,, 3-
pyrIT, ], IH, J=811z), 6
．． 69 (d.

5-J) yrJ-I, IH, J = 8)
+z), 7.34 ppm (t.

4-pyrH+ 1. H, J = 8Hz).

Reference example 3 35g of metallic sodium in 2ooml of ethanol (0,
150 mol) was dissolved therein under a nitrogen atmosphere, and indium methyl mercapta/(15% aqueous solution) 70.19
(0,150 mol) and stirred for 10 minutes, 2-chloro-6-methylsulfenylpyridine 209
(0,120 mol) was added dropwise. 2 of the reaction mixture
After refluxing for 4 hours, water is added and extracted three times with Be/Ze/. The organic layers were combined, dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The residue is distilled under reduced pressure to obtain the desired product 2.
6-bis(methylsulfenyl)
17.8& (yield s3%) is obtained.

bp 95°C/3 mm’i (g.

NMR (CC14): δ-2,80(s, CH3,
6I-I), 6.91-7.53 ppm (m,
3, 4, 5. -pyre-L3H).

Elemental analysis: C7H9NS2 Actual value (to): C49,29; H5,24; N 8.4
1 calculated value (@:C49,08;I-(5,29;N 8
．． 17 Reference Example 4 Dissolve 1.6 g of sodium metal in 20 ml of methanol, and add ethanethiol 5~ to this under a nitrogen atmosphere.
was added dropwise, and after stirring for 10 minutes, 2-bromo-6-methylpyridine 9. ] Drop j9.

After the reaction mixture is heated under reflux for 48 hours, 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. 4. Distill the residue under reduced pressure to obtain the desired 2-ethylsulfenyl-6-methylpyridine. , 5 g (yield 52%).

bpl, 07°C/15mm ■-■g.

NMR (CDCt,,): δ-1,,37(t,
-CH2CH3゜3H, J =711z), 2.4
9 (s, 6-pyr-CII3゜31-T)
, 3. ]-6(q, -CH2CH3,21-T, J-
71]→, 7, 50-6.751) I) m (m,
1) Yr, T (, 3H).

Elemental analysis゛C3I-■11NS Actual value (ftJ: C62,90; IT 7.26;
N 9.20 calculated value (to): C62,70; I (7,2
3;N In the same manner as in 9.14, the following sulfenylpyridi/s are obtained.

2-ethylsulfenyl-4-methylpyridine yield 88
% b p ]-]17~], 1.9/2], mm
, I-JgNMR(CDCl3) δ-1,36(t
, -CH2CI(3°3H,,T = 7Hz
), 2.25 (s, 4-pyr-CI■3
．． 3 H), 3.16 (q, -C 几, (J-T3. 2
H. T=7Hz), 6.78 (d, 5-
pyrl-T, ], I-I, , T = 5H
z), 6, 97 (s, 3-pYrH, ], H)
, 8. ．． 23 pprn (d.

6 - pyrH, 11 (, J = 5Hz).

Reference example 5゜2-chloro-6-,'frsulfenylhyricin 10j
i (0,063 mol) was dissolved in 100 m, e of acetic acid, and cooled to 10 to 15°C, to which was added 30% H2.
0, aqueous solution 9.2.9 (0,082 mot) was added dropwise and stirred at room temperature for 12 hours. After the reaction is completed, saturated ammonia water is added to make the mixture slightly alkaline, and then extracted three times with dichloromethane. The organic layers were combined, dried over anhydrous magnesium sulfate, and then 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 10.45. ! 9 (yield 95%) is obtained.

mp 66.0~66.5°C IR (KBr) Niji-3080,1555,14]0
゜1.120,1050 (S→O), 810,775C
7n-1°NMR (CDCt3): δ 2.74 (s, C
H3゜3■]), 7.11-7.80 ppm (m
, pYrH.

3H).

Elemental analysis: C61-I6NO8Ct Actual value (to) C40,98; If 3.45; N 7.
98 calculated value (to): C41,03; H3,44; N 7
．． Similarly to 97, the following sulfinylpyridines are obtained.

2-bromo-6-methylsulfinylpyridine yield 90
% mp76.5-77.0°c.

NMR (CCt4): δ-2,74(s, 5CI
(3.

3H), 7.25-7.86 T)pm (m, py
rl-T, 3l-T).

Elemental analysis: C6H6BrNO3 Actual value (to): C32,90; II 2.67; H6,
38 Calculated value (to): C32,74; H2,74; H6,36 5-chloro-2-methylsulfinylpyridine yield 65
% mp 52-53°c.

NMR(CDCl3)'δ= 2.85 (s
, CH3°3H), 7.98-7.94 (m,
3,4. - pyrH.

2H), 8.61-8.56 pI)m (rn,
6-pyrI(.

IH).

3.5-';'Chloro-2-methylsulfinylpyridine Yield 71% mp 95-96°c.

NMR (CDCl3): δ = 2.89 (s, C
H3.

3H), 7.82 (d, 4-pyrH, IH, J=2H
z), 8.69 ppm (d, 6-pyrH
,], II, J=2 Hz).

2-ethoxy-6-methylsulfinylpyridine yield 5
2% mp 33-35℃ NMT ((CDCl3): δ= 1.39 (t
, 0CI-T2CH3.

3 I-T, J-7Hz), 2.83 (s,
5 (0) CH3, 3H), 4.36 (q, QC and 2CI
-I3, 2 I (, J = 7 Hz), 6.7
7 (dd, 3-1) VrH, IH, J=8Hz,
J=2 Hz), 7.48-7.29 ppm (
m, 4. ．． 5-pyrH.

2H).

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

NMR (CDCz3): δ = 2.50 (s,
5CI (3゜3■(), 2.80 (s, S<0)
CH3,3H), 7.01-7.23(rn, 5-p
yrH, IH), 7.47-7.87 ppm (m,
3.4-pyrH, 2H).

Elemental analysis: C7H9NS20 Actual value (to): C44,85; H4,88; N 7.5
9 Calculated value (to): C44,89; H4,84; N 7.
472-Ethylsulfinyl-4-methylhyridine Yield 66% = 19- b p 137-139°O/6 mrn, l-1g
.

NMR (CDCl3): δ-1,20(t, -C
)-12CI-13°3 H, J = 7 Hz),
2.47 (s, 4-pyr CH3°3H),
3.28-2.47 (rn, CH2CI(3, 21
(), 7.22-7.10 (m, 5-pYrI
-T, IH), 783-7.78 (m, 3-p
yrl (, LH), 8.4.7 ppm (d.

6-pyrH, LH).

2-ethylsulfinyl-6-) fruhi IJ, :/
yyield 77% bp 103-1.04°C/4 mrttHg.

NMR (CDC73): δ = 1.21 (t, -
CH2Cl-I3゜3H, J = 714z), 2
．． 59 (s, 6-pyr-CH3°3H), 3
．． 38-2.63 (m, -CH2CH3,2H)
, 7.35-7.14 (m, 5-pyr) (, IH)
, 7.85-7.76 ppm (m, 3.4-
pyrH, 2H).

Reference example 6゜2-chloro-6-methylsulfinylhyridine 2g (0
,011mo7) and piperidi 73.62g (0,043
mol) and reflux at 120°C for 1 hour.

After the reaction, water was added, extracted with chloroform, washed with water, dried, purified by column chromatography (silica gel, chloroform), and the solvent was distilled off to obtain the desired 2-methylsulfinyl-6-
Biperidinoviridine 1.8.9 (58% yield) is obtained.

NMR (CDCl3): δ-]-,65(m, (
CI-I2)3゜6H), 2.81 (s, C
H3, 3H), 3.55 (m.

CH2N CH2, 4H), 6.60-7.77ppm
(m.

3,4,5-pyrH, 3H).

Example 1 2-chloro-6-methylsulfinylpyridine 9.42
g (0,0536 rnot) in diethyl ether (Et
20) Dissolve in 200ml and add to this in a nitrogen atmosphere.
C2H5MgBr/Et2 in IM while stirring under cooling.
Add 32 ml of 0 solution, 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 paste and extracted three times with dichloromethane. Combine the organic layers, wash with water,
After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure to obtain 332 g (yield: 55%) of the desired 6,6'-dichloro-2,2'-bipyridine.

mp: 216-217°C (11t, 218-219°
C) 3 = 7 Hz), 8.36 ppm (d
d, 3,3′-pyrH,2I-T.

J −= 7. Hz,, J"　I　Hz).

Example 2 In Example 1, 11.80.9 g of 2-bromo-6-methylsulfinylpyridine was used in place of 9.42 g of 2-chloro-6-methylsulfinylpyridine, and Example 1
．． 6,6'-dibromo-2,
4.21 g (50% yield) of 2'-bipyridine is obtained.

mp: 228~229°0(lit, 226~227°
C) 2 I-I, J = 8 Hz), 8.38
ppm (dd, 3.3'-pYrI(.

2 H, J = 7. Hz9, ff = 2Hz).

Example 3 In Example 1, instead of 9.42 g of 2-chloro-6-methylsulfinylpyridine y, 0.04 g of 2-methylsulfenyl-6-methylsulfinylpyridine was used. 1 and treated to give 6,6'-dimethylthio-2,2'-bipyridine 4,06.9 (
Yield: 61%).

mp: 130-131°CO NMR (CDC43): δ=2.67 (S + S
CH3+6 I-I), 7.17 (dd, 5.
5'-pyrH+' 2H, J=8Hi.

J・1Hz), 7.61(t, 4.now'-pyrH, 2
H, J = 8Hz), 8, 1.7 ppm (d d
, 3.3'-pyrH, 2H, J=7. H #Az
lb elemental analysis: C32HY2N2S2 Actual value (to): C58,03;I(4,87;N 11
．． 27 tears: (:'57.78; I-T 4.4
8;N 11.14 Example 4゜In Example 1, instead of 942 g of 2-chloro-6-methylsulfinylpyridine, 2-methylsulfinyl-
Using 12.02 g of 6-piperidinopyridine, Example 1. The mixture was reacted and treated in the same manner as above to obtain 380 g (yield: 44%) of 6°6'-dipiveridino-2,2'-bipyridine.

mp: 182~185°CO NMR (CDCl3): δ-1,50~1.82 (
rn.

CH2,12H), 3.45-3. s o (m,
CI-+2-N (J-12°8H), 6.55~
6.80 (m, 5J'-pYrH, 2H), 7,
35-7.82 ppm (m, 3.3:4.4'
-pyr((,4,H).

Example 5 In Example 1, 9.93.9 g of 2-ethoxy-6-methylsulfinylpyridine was used in place of 9.42 g of 2-chloro-6-methylsulfinylpyridine. 6,6'-jetoxy-
2,2'-bipyridy 1.90.9 (29%) is obtained.

mp 78-79°c.

NMR(CDC73)' δ = 1. ．． 4 3
(t, CH3,6I(.

J = 7 Hz), 4.51 (q, CH2, 4H
, J=7Hz), 6.71 (dd, 5.!i'-
pVrH, 2H, J=7Hz, J=2Hz),
7.54 (dd, 4.i'-p3/rH, 2H, J =
7Hz.

J = 7 Hz), 7. 9 7 ppm (d
d, 3.3'1) VrI-I, 2H.

J = 7 H2, J = 2 Hz).

Example 6 In Example 1, instead of 942 g of 2-chloro-6-methylsulfinylpyridine, 2-ethylsulfinyl-
Example 1 using 6-methylpyridine 9.079. 6,6'-dimethyl-2,2'
-Bipyridi/2.81 g (57%) are obtained.

mp 89-90°CO NMR (CDCl2): δ-2,62(s r CH
3+6 H), 7.14 (d, 5.5'-pyr
I-T, 2H, J=8Hz), 7.54 (t
, 4,4′-pyrI(, 2I(, J=8Hz), 8
．． 20 ppm (d, 3.3'-pyrH, 2H
, J=8Hz).

Example 7 In Example 1, 9.4.2 g of 2-chloro-6-methylsulfinylpyridine was replaced with 5-chloro-2-
Using methylsulfinylpyridine 9.4.29, Example 1. 2.41 g (4.0%) of 5°5'-dichloro-2,2'-bipyridine was obtained by reacting and treating in the same manner as above.

mp　200-202°C.

NMR (CDCt3): δ-7,77 (dd, 3
．． 3'-])yrI-T, 2H, J = 9Hz,
J=3Hz), 8.35(dd.

4,4'-pyrH,2H, J = 9 Hz,
, T = ] l1z), 8.63-8. 5 9 p
pm (m, 6.6'-1)yrl-T, 2
1-I).

Example 8 In Example 1, 9.05 g of 2-ethylsulfinyl-4-methylhyridine was used in place of 942 g of 2-chloro-6-methylsulfinylpyridine.
React and treat in the same manner as 4゜4'-dimethyl-2,2
246 g (50%) of '-Bibilisif are obtained.

m p 145-152°CO NMR (CDCt3): δ=2.41 (s,
CD3.

61-I), 7. ], 2 (d, 5,5'-
pyrl-1', 211', J=5H7,),
8,24 (s, 3,3'pYrI-T, 2
I(), 8.4.3 ppm (d+6+b'-p'
yr■■+2 T-T, J = 5 Hz).

Example 9 In Example 1, 2-chloro-6-methylsulfinylpyridine 9.429 was replaced with 3,5-dichloro-2
- Using 11.26 g of methylsulfinylpyridi7,
Example 1. React in the same way as (~, process 3, 3.' 5
．． 5'-tetrachlor-2,2'-bipyridine 4,10
ji (52%).

mp 1.03-1.04 °C6 NMR (CDCt, ): δ-7,87 (d,
4,4'-pyrH.

211, J = 211z), 8.60 ppm
(d, 6J'-pyrLT.

2 tT, , T = 211z).

Example] 0゜2-chloro-6-methylsulfinyl-IJ Syn 4
g (0,0228 mol) was dissolved in 80 ml of Et20, and 1 was added to this in a nitrogen atmosphere while cooling and stirring.
M's C6T-T 5 M g Br /E t 20
Add 1.2 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 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 the solvent was distilled off under reduced pressure.

Column chromatography (activated alumina,
To purify it with be/ze/): s, purpose 6, 6
'-dichloro-2,2'-bipyridine 1, 79 g (
Yield: 70%).

Example 11゜Example 10. In , instead of IM no C6H5MgBr/Et2o solution 12me, IM nop-CH30C6■-1+MgBr/Et was used as Klinyard reagent.
Example 10.20 using 1.2 ml of solution. 6.6'-Dichloro-2,2'-biviridi:y 1.724 is obtained by reaction in the same manner as in Treatment 1. (Yield 67%) Example 12゜Example 10. In the Grignard reagent, instead of 1.2 ml of IM's C6]5MgBr/EL2o solution, 1, M nop-CH3C6)bMgBr7E
Using t2o solution 12me, Example 10. 167 g of 6,6'-dichloro-2,2'-bipyridine was obtained by reacting and treating in the same manner as above. (Yield 65%) Example 13゜2-chloro-6-methylsulfinyl IJ) 4-
．． 5 g (0,0256mat) to Et20]
4. Dissolve in 00ml and add to this in a nitrogen atmosphere under cooling without stirring.4. )c■-■3Mg■/Et2o solution], 33m was added, and then the temperature was returned to room temperature and stirring was continued. 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 the following Example 1. 0.69 g of the desired 6,6'-dichloro-2,2'-bipyridine (yield 24%)
).

Example 14゜2-chloro-6-methylsulfinylpyridine 4,,4
5 jj (0,0253 mol) was dissolved in tetrahydrofura/(Tl(F)) 000 m, and IM C2I (5 MgB
Add 13 ml of VT T(F solution, then continue to stir at room temperature. The color of the reaction solution changes to red. A precipitate begins to precipitate. After stirring for 12 hours, water is added to the reaction mixture. was added and treated in the same manner as in Example 1 to obtain the desired 6,6'-dichloro-2,2'-bipyridine of 0.94.
9 (yield 33%) is obtained.

Patent Applicant Wako Pure Chemical Industries, Ltd. Procedural Amendment Date May 2, 1955 1 Case Description 2 Name of Invention Hypyridine i'A4 270-8571 4 Date of amendment order 5, Claims column and Detailed description of invention column of the specification to be amended.

6. Contents of correction (1) Amend the claims as shown in the attached sheet.

(2) It is characterized by reacting with a Grignard reagent represented by the formula r f4ft' R2MgX (II) described from line 14 on page 4 to line 16 on page 4 of the specification. '' is reacted with a Grignard reagent represented by the general formula R2MgX (II) (wherein R2 represents an alkyl group, an aryl group, an alkyl-substituted aryl group, or an alkoxy-substituted aryl group, and X represents a halogen). "It is characterized by causing

Attachment 2, Claims (In the formula, R1 represents an alkyl group, an aryl group, an alkyl-substituted aryl group, an alkoxy-substituted aryl group, and Y1
~Y4 is hydrogen, an alkyl group, an aryl group, an aralkyl group, an alkoxy group, a 1,000 alkoxy group, an amine group, a cyano group, a halogen group, or an alicyclic ring formed by bonding any two adjacent groups; Indicates an aromatic ring. However, at least one of Y1 to Y4 is not hydrogen. ) A method for producing a bipyridine derivative represented by (wherein Y1 to Y4 are the same as above), characterized by reacting a pyridine derivative represented by the following with a Grignard reagent represented by the general formula R2Mgx group] .

”−

Claims (1)

[Claims] (In the formula, R1 represents an argyl group, an aryl group, an alkyl-substituted aryl group, or an alkoxy-substituted aryl group, and ¥1
~¥4 is hydrogen, an alkyl group, an aryl group, an aralkyl group, an alkoxy group, a thioalkoxy group, an amino group, a cyano group, a halogen group, or an alicyclic ring formed by bonding any two adjacent groups, or Indicates an aromatic ring. However, at least one of Y1 to Y' is not hydrogen. ) is reacted with a Grignard reagent represented by the general formula R''MgX[ID]. Manufacturing method.