JPS5824437B2 - 4-Chlor-2-hydroxybenzothiazole - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION Compound 4-chloro-2-oxobenzothiazoline-3-
Yyl acetic acid (sometimes called benazoline) and its esters and salts are widely used as herbicides.

Typical salts include alkali metal salts such as sodium, and preferably potassium salts, as well as amine salts such as triethylamine or jetanolamine, and also preferably diethylamine salts.

Typical esters include C0 to C7 alkyl esters such as methyl, isopropyl esters, preferably ethyl esters.

Benazoline and its esters and salts are covered by British Patent No. 8
It was first described in No. 62226.

The process for its preparation described herein involves converting 4-chloro- (or 4-promo) 2-oxobenzothiazoline (which is also 4-chloro-2-hydroxybenzothiazole) into a compound that produces an acetate residue, such as bromo. This method involves condensation with ethyl acetate.

This specification also includes 2-oxobenzothiazoline-3
Chlorination or bromination of -yl acetic acid has also been described as an alternative method.

Although the former method is generally industrially satisfactory, it has the disadvantage that it is difficult to obtain the necessary starting materials in high yield and purity.

4-Chlor-2-hydroxybenzothiazole has been previously described in Elderfield and 5hort (J.

Org, Chem, 18.1092, (1953)) diazotization of 2-amino-4-chlorobenzothiazole in a mixture of bromine and hydrobromic acid to produce 2.
-bromo-4-chlorobenzothiazole, which is then hydrolyzed to the desired product.

In this case, the yield is 72% in the first step and 77% in the second step.
The total yield of 410-2-hydroxybenzothiazole synthesis from 2-amino-4-chlorobenzothiazole is 56%.

The manufacturing process is not satisfactory as an industrial manufacturing method.

British Patent No. 966496 discloses the conversion of 2-amino-4-chlorobenzothiazole to 2,4-dichlorobenzothiazole in high yield and the conversion of 2-amino-4-chlorobenzothiazole in high yield to 4-chloro-
A method for converting to 2-hydroxypene/''thiazole is described.

According to this method, the total yield over the entire reaction is at least 80%, which is quite satisfactory.

This method involves diazotizing 2-amino-4-chlorpentthiazole in hydrochloric acid and then hydrolyzing the dichloro compound.

It is stated that this reaction can be accelerated by the presence of a water-miscible solvent, and that particularly desirable conditions are those with the addition of benzene or toluene, with benzene providing the most satisfactory results.

The diazotization time is long, for example 16 hours or more.

Modifications of this method have previously been adopted as large-scale industrial processes.

In this improved process, 2-amino-4-chlorobenzothiazole hydrobromide is introduced into a mixture of 2,4-dichlorobenzothiazole and 2-7''Omu-4-chlorobenzothiazole; Hydrolysis yields 4-chloro-2-hydroxybenzothiazole.

Although the yield of 70 to 80% obtained by this method is much better than the 56% yield obtained by the above-mentioned method, there still remains an industrially undesirable portion.

That is, long reaction times are required to achieve this yield.

Additionally, this 4-chloro-2-hydroxybenzothiazole is contaminated with a significant amount of desirable c-tl organisms, which are generally removed near the end of the entire process for producing benazoline or its esters or salts. must be carried out.

It is clear that this special purification step is time consuming as well as cost disadvantageous, and should be avoided if possible.

Furthermore, the formation of this unnecessary by-product is also a loss of starting materials.

Therefore, it is an object of the present invention to produce 4-chloro-2-hydroxybenzothiazole as an intermediate for the production of benazoline and its esters and salts in a manner with higher purity and higher yield than the methods conventionally carried out on an industrial scale. , and also provide a method for obtaining it in a short reaction time.

The present invention was completed based on the discovery that by using a specific water-immiscible solvent for diazotization, it is possible to surprisingly improve yield, purity, and shorten reaction time.

That is, according to the method of the present invention, benazoline and its esters and salts can be obtained with such high purity that only a small amount of impurities are present and the above-mentioned purification step is no longer necessary.

Also, according to the method of the present invention, higher yields than previously obtained can be achieved with the same reaction times used in the aforementioned methods, and satisfactory with much shorter reaction times than used in the aforementioned methods. high yields can be achieved, and losses of starting materials can be reduced.

In the present invention, in producing 4-chloro-2-hydroxybenzothiazole by diazotizing 2-amino-4-chlorobenzothiazole hydrohalide and hydrolyzing the product, diazotization is performed by diazotization reaction. This method is carried out in the presence of a halogenated aliphatic hydrocarbon solvent in which the main product is dissolved to at least 10% W/V at 20°C.

The main product of the diazotization reaction is 2-halo-4-chlorobenzothiazole.

When 2-amino-4-chlorobenzothiazole is used in its preferred hydrobromide salt form, the main product is 2-bromo-
4-chlorobenzothiazole.

Usually, 2,4-dichlorobenzothiazole is also produced.

Preferred logenated aliphatic hydrocarbons used in the present invention include particularly preferred ethylene dichloride, as well as methylene chloride, chloroform, carbon tetrachloride, tetrachloroethylene (barchlorethylene), 2-dichloropropane,
(2) 1.1-trichloroethane and ethylene tribromide.

The diazotization reaction is carried out at a temperature below 30°C, for example between 20 and 20°C.
At 5°C, usually more than IN, preferably 5.5 to 6
．． Preference is given to carrying out in hydrochloric acid having a concentration of 5N.

This reaction is also preferably carried out in the presence of acetic acid.

The amount of organic solvent is not particularly limited, but it is preferably at least 20% by volume of the total reaction mixture, such as from 25 to 60% by volume.

The diazotization reaction generally takes less than 2 hours but more than
In this case, it will last for 7 hours, on average about 5 hours.

The reaction generally continues until the solid material suspended in the aqueous phase has substantially disappeared.

The organic phase is then separated and preferably evaporated to dryness before hydrolysis.

Hydrolysis can be carried out by reaction with a mineral acid, such as hydrochloric acid, preferably in the presence of a water-miscible solvent, such as methanol, ethanol or technical methanol denatured alcohol.

Hydrolysis is suitably carried out at a temperature of 50 to 150°C, preferably under reflux.

The product can be isolated using conventional methods.

Then optionally benazoline, for example as described in British Patent No. 9.
It can be converted by the method described in No. 66496.

According to the method described in this specification, 4-chloro-2-
Hydroxybenzothiazole as ACH2B or R,0
In the presence of a compound selected from CR2CN (wherein A is a halogen atom, B is a carboxy group or a salt thereof, ester, amide or nitrile, and R1 is an alkanesulfonyl or 7-lenesulfonyl group) and an alkali condensing agent. Condensation is carried out to obtain a compound represented by the formula (1), and if necessary, B is converted into a desired group selected from carboxyl or a salt or ester thereof as described above.

By using the above-mentioned solvent, it has been possible to improve the yield and shorten the reaction time compared to the conventional method, but in the present invention, a halogenated aliphatic hydrocarbon selected from the above-mentioned specific group is used as the solvent. A further important advantage is obtained by using .

It is 2-amino-4-chlorobenzothiazole...
Hydrologenide salts can be prepared by cyclization of N-2-chlorophenylthiourea in the same solvent system used in the subsequent diazotization reaction, resulting in 2-amino-4
After producing the -chlorobenzothiazole hydrohalide salt, it became possible to directly react it in the same solvent system without isolation prior to the diazotization step.

As a result of eliminating the need to isolate this compound prior to diazotization, the overall yield and time required for the entire process for producing benazoline from N-2-chlorophenylthiourea is significantly improved.

Cyclization of N-2-chlorophenylthiourea to form 2-amino-
In producing 4-chlorobenzothiazole hydrohalide, thiourea is reacted with a chlorine or bromine source in the aforementioned logenated aliphatic hydrocarbon solvent.

A preferred chlorine source is sulfuryl chloride and a preferred bromine source is bromine.

The reaction temperature is preferably 30 to 100°C.

Next, the present invention will be explained by examples.

In the examples, "%" means "% by weight".

The yield is for pure material, so the actual yield (with slight impurities) is slightly higher than the indicated value.

Example 1 2-Amino-4-chlorobenzothiazole hydrobromide (79f) and ethylene dichloride (3oOrrtl) were added to a mixture of concentrated hydrochloric acid (114ml), glacial acetic acid (78ml) and water (114TLl) in 11 flasks. Add inside.

Sodium nitrite (41f) in water (67 ml) was added to the whole mixture while stirring and keeping it at 20-25°C with water cooling.
The solution is added at a constant rate over a period of 2 hours.

The mixture is stirred for a further 2 hours.

Water (100 ml) is added and the lower layer is separated and evaporated to dryness.

The residue was dissolved in industrial methanol-modified 7 alcohol under hot conditions, refluxed vigorously, and concentrated hydrochloric acid (182 rrLl) was added under stirring.
Add in 2.5 hours.

Continue stirring and heating for an additional 2 hours.

The mixture is then cooled to below 30°C and water (182ml) is added.

Collect the solids, wash until acid-free, and store in vacuo for 60 minutes.
Dry at °C.

The 4'-chloro-2-hydroxybenzothiazole thus obtained exhibits a purity of 95% when titrated with tetrabutylammonium hydroxide in acetone.

Yield 83%. Example 2 The procedure is as in Example 1, substituting the equivalent volume of methylene chloride for ethylene dichloride.

The purity of the obtained 4-chloro-2-hydroxybenzothiazole is 95% and the yield is 87%.

Example 3 N-2-chlorophenylthiourea (6El') is added to a mixture of glacial acetic acid (48 ml) and ethylene dichloride (195 ml) in a 11 flask.

Stir the mixture vigorously and add bromine (61,51?) in one portion.

Once the temperature has stopped rising, the mixture is boiled under reflux for 4 hours.

Next, cool to 15-20℃ and add concentrated hydrochloric acid (1157711)
and water (115 ml).

Sodium nitrite (
Add the aqueous solution of 4i) in 2 hours.

The following procedure is carried out in the same manner as in Example 1 to obtain 4-chloro-2-hydroxybenzothiazole.

Purity 95%, yield 83%.

Example 4-9 Equivalent volume of chloroform instead of ethylene dichloride (Example 4)
, tetrachlorethylene (Example 5), ■・1,1-trichloroethane (Example 6), ■・2-dichloropropane (Example 7)
), ethylene tribromide (Example 8), and double the volume of carbon tetrachloride (Example 9).

The purity of 4-chloro-2-hydroxybenzothiazole obtained on each side is 93-95%, and the yields are 73%, 66%, 65%, 72%, 61% and 71%, respectively.

The yield will be higher if the diazotization reaction time is increased.

Example 10 Glacial acetic acid (48 ml) and ethylene dichloride (36771
N-2-chlorophenylthiourea (65
This is gradually added to a solution of bromine (61,52) in ethylene dichloride (97 ml) with stirring.

During this time, keep the temperature below 55°C by cooling with water.

Carefully heat the mixture until reflux and bring to this temperature for 4
Hold time.

The mixture is then cooled to 15 to 20 DEG C. and treated in the same manner as in Example 3 to obtain 4-chloro-2-hydroxybenzothiazole.

Purity 95%, yield 84%. Example 11 4-chloro-2-hydroxybenzothiazole (185-5P) obtained in Example 1 was mixed with anhydrous potassium carbonate (185-5P).
3&5S'), sodium iodide (5 g) and methyl ethyl ketone (11).

While stirring and refluxing the mixture, chloroacetic acid ethyl ester (13El) is added.

The mixture was refluxed for a further 4 hours and water (280ml)
is added and the mixture is cooled to 70°C.

The aqueous layer was discarded and the organic layer was evaporated to dryness, and the resulting oil was dissolved in refluxed industrial methanol-denatured alcohol (200 ml).

Aqueous sodium hydroxide solution (2.5N, 440ml) is added and reflux is continued for 2.5 hours.

The solution is then cooled and acidified to pH 1 to 2 with hydrochloric acid.

The product obtained is filtered, washed with water and dried to give benazoline, melting point 185-8°C.

Example 12 Similarly to Example 11, 4 obtained in Examples 2 to 9
Benazoline is obtained from -chloro-2-hydroxybenzothiazole.

Comparative Example In Example 1, benzene was used instead of ethylene dichloride, the addition of nitrous acid was carried out for 5 hours instead of 2 hours, and stirring continued for 16 hours instead of 2 hours.

77% 4-chloro-2-hydroxybenzthiazole
The purity obtained with a yield of 4-
Contaminated with 8.3% chloro-2-phenylbenzothiazole.

It is difficult to remove this at this stage.

When this product is converted to benazoline in the manner described in Example 11, it is necessary to remove this impurity by extraction with methylene chloride after hydrolysis with sodium hydroxide.

The embodiments of the present invention are as follows.

(1) The method according to the claims, wherein the solvent is a chlorinated hydrocarbon.

(2. The method according to the claims, wherein the solvent is ethylene dichloride.

(3) In the claimed method, the solvent is methylene chloride, chloroform, carbon tetrachloride, tetrachloroethane, trichlorethylene, perchloroethylene, 1.1.
A method selected from the group consisting of 1-trichloroethane, dichloropropane and ethylene tribromide.

(4) In the claimed method, diazotization is carried out in hydrochloric acid.

(5) In the claimed method, diazotization is carried out in the presence of acetic acid. (6) In the claimed method, a rogogenated aliphatic hydrocarbon solvent solution resulting from diazotization is reacted. Separation from the medium and evaporation to dryness before hydrolysis of the product.

(7) In the method of the claims, the hydrolysis is a method in which a mineral acid is used. (8) In the method in the Uemachi η section, the mineral acid is a method in which hydrochloric acid is used.

(9) In the method of the claims, 2-amino-4
Chlorbenzothiazole is prepared by cyclization of N-2-chlorophenylthiourea in the same solvent system as used in the next diazotization reaction, and is directly used in the next diazotization reaction without being isolated from this solvent system. How to attach to.

αO) In the claimed method, the obtained 4-chloro-2-hydroxybenzothiazole is combined with ACH2B and R10CH2CN (wherein A is a halogen atom, B is a carboxyl group or a salt thereof, an ester, an amide or a nitrile Next day, R1 is condensed with a compound selected from haalkanesulfonyl or haalenesulfonyl group in the presence of an alkali condensing agent to obtain a compound represented by formula (2), and if necessary, B is converted to carboxyl or a salt thereof or A method of converting the ester into a desired group selected from the ester.

Claims (1)

[Scope of Claims] A compound of the formula 1 (wherein B is a carboxyl group or a salt thereof) is combined with 4-chloro-2-hydroxybenzothiazole (wherein A is a ~rogen atom and B is the above-mentioned compound). In the method of producing 4-chloro-2-hydroxybenzothiazole, 2-amino-4-chlorobenzothiazole hydrohalide ethylene dichloride, methylene chloride, chloroform, etc., in which the main product of the diazotization reaction is dissolved to an extent of at least 10% W/V at 20°C. , carbon tetrachloride, tetrachloroethylene (perchlorethylene), ■・1・1−
g) A method characterized in that it is carried out in the presence of a logogenated aliphatic hydrocarbon solvent selected from chloroethane, ethylene tribromide and 1,2-dichloropropane.