JPS58154561A - Preparation of 2-hydroxyhalogenopyridine - Google Patents

Abstract

PURPOSE:To prepare selectively a 2-hydroxyhalogenopyridine useful as a raw material for agricultural chemicals, etc., by hydrolyzing a halogenopyridine with an alkali aqueous solution using a phase transfer catalyst such as a quaternary ammonium salt, quaternary phosphonium salt, etc. as a catalyst. CONSTITUTION:A halogenopyridine (e.g., 2,3-dichloropyridine, etc.) shown by the formulaI(X is halogen; n is 2-4) is hydrolyzed with an alkali aqueous solution (e.g., >=50wt% NaOH aqueous solution, etc.), to give a 2-hydroxyhalogenopyridine shown by the formula II. In the reaction, a phase transfer catalyst such as benzyltriethylammonium chloride, tetraphenylphosphonium chloride, 18- crown-6, etc. or a nitrogen-containing heterocylic compound such as pyridine, etc. is used as a catalyst.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing 2-hydroxydihalogenopyridine.

More specifically, it relates to a catalyst for alkaline processing of halogenopyridine.

2-Hydroxyhalogenopyridine is a compound useful as a raw material for the synthesis of organic compounds, for example, as an intermediate raw material for agricultural products, and has been increasingly used in recent years.

Conventionally, as for the method of preparing 2-hydro-dihalogenopyridine, various methods are known, for example, US 8,
No. 355,456 describes a method in which 2,6-dihalogenopyridine or 2,4-dihalogenopyridine is reacted with Ashikali hydroxide using 1M canol as a solvent, and 5yntk@sis 1974 (1G), TO
? 4: is a method in which 2.6-dichloropyridine is reacted with potassium t-butoxy in t-butyl acetate,
In addition, in 1873-1873 Ganko, a method of reacting halogenopyridine with a carbon end metal salt such as potassium acetate was described.

What is halogenopyridine used in the present invention? , s-dichloropyridine 2.5-dichloropyridine, g, @-dichloropyridine, z, 6-dichloropyridine.

2-chloro-6-fluoropyridine, 2-chloro-6-
Bromopyridine, 2,3.5-)dichloropyridine,!
, 1. i! -) Dichloropyridine, 2,3°5.6-
Tetrachloropyridine, 2,3-zigumoviridine. 2
．． 5-diglomoviridine, 2,6-dibromopyridine,
2-Chloro-3-bromopyridine.

2-chloro-3-bromopyridine, 2,3.5-)dibromopyridine, Z, 8,6-tribromopyridine, 2
-Bromo-3,5-dichloropyridine, z,3-dichloro-5-bromopyridine. 2.3-diglomo, 5-chloropyridine, 2,5-dichloro-3-bromopyridine,
2,5-dibromo-3-chloropyridine, 8. @-dibromo-3-chloropyridine.

2,6-dichloro-3-chloropyridine, 2,6-dichloro-3-bromopyridine, 2,3-dichloro-3-chloropyridine
Promoviridine, 2,3-dibromo-6-chloropyridine, 3,5-dichloro-2-bromopyridine. 3.5-
In addition to diglomo-2-chloropyridine and the corresponding fluorine substituted products, 2.3.5.6-titrapromoviridine, snow, 6-dipromo-3-1-dichloropyridine, 2.6-difluoro-3, 5-dichloropyridine, ! ,! , S, 6-titrafluoropyridine, etc. Refers to compounds having 2 to 4 halogen substituents including the 2 position at the four positions of pidgin S , S , S , . . . There is only one snow position II
All compounds substituted with a tOH group and without a substituent at position 4 are subject to **. Examples of this include 2-hydro-1-chloropyridine, 2-hydroxy-3-bromopyridine, 2-hydroxy-3-bromopyridine, 2-hydroxy-3-bromopyridine, 2-hydroxy-3-bromopyridine,
-ζ-droxy-5-resin m-hydro-5-gromovitudine, 2-r-droxy-5-fluoropyridine, 2-hydro-chloropyridine, hydro-6-promoviridine, Olobiridine in 2-hydro and 6-ph.

2-hydroxy-3,5-dichloropyridine, 3-hydro-3,5-dibromopyridine, S-hydroxy-3,5-difluoropyridine, 2-hydro-3.6
-dipromopyridine, 2-hydro-3,6-dichloropyridine, 2-hydroxy-3,6-diphropyridine, 2-hydroxy-3-chloro-5-bromopyridine, 2-hydroxy-3-chloro- 5-fluoropyridine, 2-hydroxy-3-chloro-6-bromopyridine, 2-L 3-chloro-6-fluoropyridine.

2-Hydroxy-3-bromo-5-chloropyridine, 2
-hydro-3-bromo-5-fluoropyridine, 2
-Hydroxy-3-bromo-6-chloropyridine, 2-
Hydroxy-3-bromo-6-chloropyridine, 2-hydro-3-fluoro-5-chloropyridine, 2-hydro-3-fluoro-5-bromopyridine, 2-hydro-3-fluoro-6-chloropyridine, 2-hydro-3-fluoro-6-promoviridine, 2-hydroxy-3,5,6-)lichloropyridine, 2-hydro-3.5.6-tribromo and lysine, 2-hydroxy-3, 5,6-) Oropyridine in the riff.

2-hydrocarbon 3.5-dichloro-6-bromopyridine, 2-hydroxy-3,5-dichloro-6-fluoropyridine, 2-hydrocarbon 3. s-dibromo-6-chloropyridine, 2-dibromo-6-chloropyridine, s-3,5-dibromo-6
-fluoropyridine, snow-hydroxy-3,5-difluoro-6-chloropyridine, 2-hydroxy-3,5-
cifudio a-6-bromopyridine, 2-hydro cyi 3
．． 6-ditaro-5-bromopyridine, snow-L dorochusea 3.・-dichloro-5-fluoropyridine, 2-hydro-sea 3-dipromo-5-chloropyridine,! - human p+cy 3,6-dipromorph 5-ph with orobidazine;
2-hydro-3,6-difluoro-S-chloropyridine, 2-hydroxy-3,6-difluoro-5-bromopyridine, 2-difluoro-5-bromopyridine, 1-chloro)promo 6
-Fluoroviridine, 8-hydro-3-reglow S
・-Fluoro-・-bromopyridine, 2-human awIF
C-3-promo-chloro-6-fluorobiridine,
2-hydroxy-3-bromo-5-fluoro-6-chloropyridine, 2-hydroxy-3-fluoro-5-chloro-6-bromopyridine, 2-hydro-3-fluoro-5-promo-6-chloropyridine etc.

In this way, according to the present invention, position 2 is 11i! It is characterized in that only I is selectively equipped with a halogenopyridine substituted with an -OH group.

The alkali used in the present invention is preferably an aqueous solution with a concentration of 50% or more, and usually a sodium hydroxide aqueous solution or a potassium hydroxide aqueous solution is used, but it is preferable to use a 60% aqueous solution of sodium hydroxide, or Just add sodium hydroxide and water at once and adjust so that one button is added. If the alkali content is less than 50%, the reaction rate will be severely slowed down and the reaction will have to be carried out under mixed pressure, which is not preferable in terms of MA, but the concentration will increase.
The handling will be 4-. The amount of potassium added to 7 is preferably 1 to 10 gFl&# with respect to the raw material halogenopyridine, and more preferably L (8 to Sθ gives good results. If it is too small, the reaction will not proceed, and if it is too large, the reaction will not proceed. It is not advantageous because it tends to cause a reaction.

Aiko transfer used as a catalyst - What is it as a catalyst? ) trimethylammonium chloride (TMAC)” to pendyltrimethylammonium chloride F (!ITMAC) benzyltrimethylammonium chloride (BTEmC) pendyltriptylammonium chloride (flTBAc)
), tetrabutydiammonium bromide (TIAB)
, Tetrabuti (78AH5).

K ammonium hydrogen sulfz TT 1-octyl methylammonium chloride (TOM C), N-lauryl pyridinium chloride (PYLC), N-lauryl 4-pyridinium va94 FC4PCLC) t
N-49111kI and al=9a chloride (M P
CL C), N-hen! ;w I'av
1o54 FCMPCjlC), 11d1)94
@Ammonium dust, tetraphenylphosphonium chloride (TPPC), tetrabutyl phosphonium chloride (TBPC),) lyobutyl ethylphosphonium bromide (TONf'B), etc. f) $49 Phosphonium salts, 18-crown-6 (18-C) -6),
Dicyclohexyl-18-crown-6 (DC-18-
C-6), dibenzo-18-crown-6 (DB-18
-C-6), crown ether II such as (2,2,2
) - Cryptands such as taleptate, polyethers such as polyethylene glycol and polyethylene glycol digdel ether are all effective, among which mohenzyl triethylammonium chlorite.

Tetrafuchi hair ammonium bromide tetrapheni~
Phosphonium chloride, 18-crown-41, polyethylene glycol with a molecular weight of 600, [2°2.2]-
#4 IIIt ammonium salts such as cributate, quaternary phosphonium salts, borieates, etc. have high yields.
Nitrogen heterocyclic compounds, especially pyridine, have shown favorable effects in terms of cost, economy, and durability.

In some cases, it may be more effective to mix 2111 or more of these catalysts.

The amount of these catalysts to be added cannot be definitively determined as the appropriate amount depends on the woodcutter of the catalyst, but generally it is 0.0 to halogenopyridine.
A range of 1 to 0.8 times mole, particularly o, oz to o, -1 mole, is suitable. If it is less than this, the effect will be visible, but if it is more than this, the effect will not increase that much, so it is not a good idea.

To carry out the method of the present invention, a conventional reaction apparatus may be used, and a predetermined amount of halogenopyridine is added to the reaction vessel.

Add an alkaline water bath solution and a catalyst, and heat for a predetermined period of time to cause a reaction. Alkaline wrinkles can be added in an amount equal to or more than the weight of NA, but the reaction results are rarely influenced by the amount of NA, and the amount of alkali added is usually about 2 to 5 times higher. The reaction temperature is 1
It is heated and maintained at a temperature of 00°C to 200°C, preferably 120°C to 150°C. If the al degree is low, the reaction rate will be slow, and if it is too high, one reaction, decomposition, etc. will occur, which is undesirable.

Hereinafter, the present invention will be explained in further detail by showing 14 actual examples.

Example 1 2,6-dichloropyridine 10K (67,6mmo
l), 1 m/ml of a 50% aqueous solution of benzene triethylammonium chloride was added to 15 g of NaQd and 9 g of water.

The mixture was maintained at 120° C. to 130° C. and reacted for 8 to 1θ hours while stirring. After neutralization with hydrochloric acid, the product was extracted with chloroform. The yield was 95.7%. Further, the roform phase was concentrated to dryness and the residue was recrystallized from methanol L5. :lr white crystals were obtained. One point is 129~l
at 'C, and the molecular weight according to the mass spectrum is 1
It was 29. The kLl spectrum also matched that of standard 2-hydro-6-chloropyridine.

Fruit-H2 2,3,5,6-chitrakalohiriji 710g (48
11 ml of a 50% aqueous solution of ammonium chloride was added to 10 g of NaOH (mmol) and 6 g of water, and the mixture was kept at 146° C. and stirred for 1 hour to react. −
After neutralization with 100% of toluene, the product was neutralized with 100% of toluene. IJF
Extraction was carried out at 5 degrees of heat. The yield was 91.2%. By cooling the toluene phase, 7.02 g of 3. ! 1.
41-Trichlorou-2-viridinol was obtained. One point is 1
The temperature was 14 to 175°C, and the molecular weight according to mass spectrometry was 197.

Examples 3 to 16 z, a, s, e -t trial port a Pyridine (TCP-containing hydroxide) lium, water viscosity, and catalyst were heated and reacted under the conditions shown in Table 1 with stirring. The HL reaction mixture was cooled to room temperature, acidified with 1 concentrated salt, and the product was analyzed by gas chromatography in 4 fil, 1, II fractions.

The results of the production of 6-dolichloro-2-viridinol are shown in Table 1.

Table 1 Examples 20 to 26 Various halogenopyridines 101r were used as raw materials, and benzyltriethylammonium chloride 50 was used as a catalyst.
The reaction mixture was heated and reacted with stirring under the conditions shown in Table 92. The reaction mixture was cooled to room temperature, and the acidity and L1 product were analyzed by gas chromatography to determine the melting point.

The results of the production of the corresponding 2-hydroxyhalogenopyridine are shown in Table 2.

I2 table

Claims (1)

[Scope of Claims] (1) 2-hydroxy represented by the general formula, characterized in that the halogenopyridine represented by the general formula is hydrolyzed by adding an aqueous potassium solution to a in the presence of at least l Hashihata's catalyst. Method for producing halogenopyridine. (2) Claim (1) in which the halogen is m-element
Method described. (3) Claim 11 (method of a&54+1) in which the halogenopyridine is 2,6-dichloropyridine. (4) Patent in which the catalyst is a phase transfer catalyst (
1) Ki's method. (5) The method according to claim 1t(4), wherein the catalyst is 4@ammonium salt IIIN''e. (6) The method according to claim 1, wherein the quaternary ammonium salt is benzyltriethylammonium chloride Method. (7) The method according to claim (4), wherein the catalyst is a 4m phosphonium salt. (8) The method according to claim 4, wherein the 4m phosphonium salt is tetraphenylphosphonium chloride.
the method of. (9) The method according to (4), in which the catalyst is a crown ether. αO) The method according to (9), wherein the crown ether is 18-crown-6. (Separate) Patent claim where the catalyst is polyether - (4)
Method described. (12) Polyether has 1 molecule of 300 to 200
00 polyethylene glycol (
11) Kikai's method. (13) Claim H(4) Kikai's method, wherein the M medium is a cryptand. (14) Claims #V-Claims in which the cryptands are (2,2,2)-cryptands (method described in 13J). (15) Claims in which the catalyst is a Vli-containing node-like compound (1) One method. (16) A patent in which the nitrogen-containing compound is pyridine! (The method described in the 15J journal. The special feature that is llll'Fm*f) [11 (15)
Law. (18) The method of claim M(1)g@, wherein the catalyst is a mixture of lysine and a correlated Ilk catalyst.