KR20090012625A - Process for preparation of disodium stilbenedisolfonates - Google Patents

Abstract

A method of benzene sulfonic acid sodium salt is provided to raise purity and yield of a final Int-2 by minimizing impurities of the Int-2 and to show series processing usable commercially. A method of benzene sulfonic acid sodium salt indicated as a chemical formula 1 comprises: reacting a compound of a chemical formula 2 and a compound of a chemical formula 3 and producing a compound of a chemical formula 1 and a compound of a chemical formula 4; adding a compound of a chemical formula 5 to the generated mixture and producing the compound of a chemical formula 1 and a compound of a chemical formula 6; adding a compound of a chemical formula 7 to the generated mixture and producing the compound of a chemical formula 1; and manufacturing a final compound(the chemical formula 1).

Description

Process for preparation of disodium stilbenedisolfonates with amino triazine-substituted sodium stilbenesulfonate salt

The present invention relates to a method for preparing sodium stilbendisulfonic acid salt substituted with amino triazine as an intermediate of fluorescent brightener.

The present invention relates to a method for preparing a compound represented by Formula 1, and more particularly, a) reacting a compound of Formula 2 with a compound of Formula 3 to produce a mixture of Formula 1 and Formula 4 ; b) adding a compound of Formula 5 to the mixture produced in step a) to produce a mixture of Formula 1 and Formula 6; c) adding a compound of Formula 7 to the mixture produced in step b) to produce a compound of Formula 1; And d) separating and purifying to obtain the final compound (Formula 1); It relates to a method for producing sodium benzene sulfonate salt comprising a.

[X is a straight or branched saturated or unsaturated (C ₁ -C ₁₀ ) alkyl, (C ₁ -C ₇ ) alkoxy, (C ₁ -C ₇ ) alkoxy (C ₁ -C ₇ ) alkyl, (C _1- C ₇ ) alkoxycarbonyl, (C ₁ -C ₇ ) alkoxycarbonyl (C ₁ -C ₇ ) alkoxy, (C ₁ -C ₇ ) alkoxycarbonyl (C ₁ -C ₇ ) alkylamino, (C _1- C ₇₎ alkoxycarbonyl (C ₁ - C ₇₎ alkyl, aminocarbonyl, (C ₁ - C ₇₎ alkylcarbonyloxy (C ₁ -C ₇₎ alkoxycarbonyl, hydroxy, cyano, nitro, amino, Mono or di (C ₁ -C ₇ ) alkylamino, mono or di (C ₁ -C ₇ ) alkylaminocarbonyl, mono or dibenzylamino, mono or di (C ₁ -C ₇ ) alkylamino (C _1- C ₇ ) _{3 to 7 comprising} at least one alkoxy, (C ₃ -C ₇ ) cycloalkylamino, (C ₁ -C ₇ ) alkylcarbonylamino, aminocarbonyl, oxygen, nitrogen or sulfur in the heterocycle Unsubstituted or substituted saturated or unsaturated heterocycloalkyl, mono or di halogen (C _1- C ₇ ) alkylsulfonamino, morpholin, morpholin oxide, piperazine, piperazine oxide, guanidine, (C ₁ -C ₇ ) alkylguanidine, urea, (C ₁ -C ₇ ) alkylurea, phenyl , Phenoxy, benzyl, benzyloxy, thiobenzyl, carboxylic acid, carboxyl (C ₁ -C ₁₀ ) alkylamino, carboxyl (C ₁ -C ₁₀ ) alkylaminocarbonyl, (C ₁ -C ₇ ) alkyl Ketones, and benzoyl].

The compound of formula 1 is used throughout the chemical industry as an intermediate of a compound that is used as a whitening agent for textile products by substituting organic substituents such as morpholine, morpholine oxide, piperazine, piperazine oxide and guanidine. . A general method for preparing the compound of Formula 1 is shown in Scheme 1 below. 1) 4,4'-Diamino-2,2'-Stilbenesulfonic acid (4,4'-Diamino-2,2'-stilbenedisulfonic acid , Hereinafter referred to as 'DAS') with sodium sulfonate salt, and 2) cyanuric chloride (2,4,6-trichloro-1,3,5-triazine) in the product (1) After the addition of Chemical Formula 5), ammonia aqueous solution was added to the product of 3) 2) (hereinafter referred to as 'Int-1') to give benzenesulfonic acid, 2,2 ′-(1,2-ethendiyl) bis [5- [ 4-amino-6-chloro-1,3,5-triazin-2-yl] amino] -disodium salt (Benzenesulfonic acid, 2,2`- (1,2-ethenediyl) bis [5-[[4 -amino-6-chloro-1,3,5-triazin-2-yl] amino] -disodium salt, hereinafter referred to as 'Int-2').

This method is described in patent WO 2004/069790. Int-2 in the above reaction may be used a variety of organic substituents in addition to the amino group in the present invention will be described by way of example the amino group shown in the literature. In the preparation method as described above, since the compound of Equation 5 not reacted with cyanuric acid (Cyanuric acid), which is a hydrolyzate of Formula 5, is left in the preparation of Int-1, the conversion rate of Int-1 The problem is that this is only about 88-93%. In addition, in the case of commercial production there is a problem that by-products such as cyanuric acid increases by 15%. In addition, there is a problem that the following by-products are generated in the preparation of Int-2.

Since the by-products have similar properties to Int-2 and high boiling point, separation and purification are difficult, so that the overall conversion rate of Int-2 has a low conversion rate of 70 to 73%. In addition, by introducing other substituents such as Morphorine and the like in a continuous process with the above by-products and replacing them with chlorides of Int-2, 5 to 11% of unreacted Int-2 remains, The conversion of substituted compounds is also lowered to 60-70%. In addition, since impurities generated by the by-products of Int-2 are not easy to purify, a low purity compound having a purity of 82 to 85% of a compound substituted with morpholine is produced.

In addition, USP 4,552,959 introduces a method of first substituting an amino group to a compound of Formula 5 and then substituting DAS, but the method of 2-amino-4,6-dichloro-1,3,5-triazine (2 -Amino-4,6-dichloro-1,3,5-triazine (hereinafter referred to as 'ADT') produces side reactions in which only one of the amino groups of the DAS is substituted. It is not easy to separate and purify, and if the process is continuously carried out to the final material without removing the side reactions, the side reactions and by-products of the side reactions are included in the final material, causing problems such as lowering of crystallinity and lowering purity. This makes the final material less commercially viable. Therefore, in order to reduce the above side reactions, ADT is added in excess of the equivalent ratio of DAS or high temperature reaction occurs.When ADT is added in excess of the equivalent ratio, the melting point of ADT is 230 ℃, so it is difficult to separate in continuous process. In other words, the excessive amount of ADT, which remains in excess, causes the formation of side reactions that continue in the next step, resulting in lower overall yield and purity.

Therefore, the present invention uses a dichlorotriazine substituted in position 2 in order to solve the above problems, it is substituted on both sides of the amine group of the compound of Formula 3 to minimize impurities substituted only one amine group, and The purpose of the present invention is to propose a method of manufacturing a commercially available continuous process by increasing the purity and yield of the final Int-2 by minimizing the impurities of Int-2.

In order to achieve the above object, the present invention provides a manufacturing method as follows.

The present invention provides a method for preparing a compound represented by the following formula (1),

a) reacting a compound of Formula 2 with a compound of Formula 3 to produce a mixture of Formula 1 and Formula 4;

b) adding a compound of Formula 5 to the mixture produced in step a) to produce a mixture of Formula 1 and Formula 6;

c) adding a compound of Formula 7 to the mixture produced in step b) to produce a compound of Formula 1; And

d) separating and purifying to obtain a final compound (Formula 1); It relates to a method for producing sodium benzene sulfonate salt comprising a.

[Formula 1]

[Formula 2]

[Formula 3]

[Formula 4]

[Formula 5]

[Formula 6]

[Formula 7]

[X is a straight or branched saturated or unsaturated (C ₁ -C ₁₀ ) alkyl, (C ₁ -C ₇ ) alkoxy, (C ₁ -C ₇ ) alkoxy (C ₁ -C ₇ ) alkyl, (C _1- C ₇ ) alkoxycarbonyl, (C ₁ -C ₇ ) alkoxycarbonyl (C ₁ -C ₇ ) alkoxy, (C ₁ -C ₇ ) alkoxycarbonyl (C ₁ -C ₇ ) alkylamino, (C _1- C ₇₎ alkoxycarbonyl (C ₁ - C ₇₎ alkyl, aminocarbonyl, (C ₁ - C ₇₎ alkylcarbonyloxy (C ₁ -C ₇₎ alkoxycarbonyl, hydroxy, cyano, nitro, amino, Mono or di (C ₁ -C ₇ ) alkylamino, mono or di (C ₁ -C ₇ ) alkylaminocarbonyl, mono or dibenzylamino, mono or di (C ₁ -C ₇ ) alkylamino (C _1- C ₇ ) _{3 to 7 comprising} at least one alkoxy, (C ₃ -C ₇ ) cycloalkylamino, (C ₁ -C ₇ ) alkylcarbonylamino, aminocarbonyl, oxygen, nitrogen or sulfur in the heterocycle Unsubstituted or substituted saturated or unsaturated heterocycloalkyl, mono or di halogen (C _1- C ₇ ) alkylsulfonamino, morpholin, morpholin oxide, piperazine, piperazine oxide, guanidine, (C ₁ -C ₇ ) alkylguanidine, urea, (C ₁ -C ₇ ) alkylurea, phenyl , Phenoxy, benzyl, benzyloxy, thiobenzyl, carboxylic acid, carboxyl (C ₁ -C ₁₀ ) alkylamino, carboxyl (C ₁ -C ₁₀ ) alkylaminocarbonyl, (C ₁ -C ₇ ) alkyl Ketones, and benzoyl].

As described above, when the compound of Formula 5 is directly substituted with the compound of Formula 3, many side reactions occur in the next step. In order to overcome this problem, the compound of Chemical Formula 1 is first produced to react with Chemical Formula 3 to prepare Chemical Formula 1. In the process, Formula 4, which is generated together with Formula 1, is added to Formula 5 to prepare Formula 6, and to which Formula 7 is added to substitute the compound of Formula 1 to produce the above side reaction product. You can reduce the production.

Since the compound of Chemical Formula 2 is lower in reactivity than the compound of Chemical Formula 5, the compound of Chemical Formula 4, which is not reacted, is present, which is difficult to separate and purify. In order to overcome this, it is preferable to minimize the remaining compound of Formula 2 by reacting the compound of Formula 2 with 1 to 2 equivalents with respect to the compound of Formula 3. When the compound of Formula 2 is more than 2 equivalents to the compound of Formula 3, it is difficult to separate and purify the remaining compound of Formula 2 as described above. In addition, if less than 1 equivalent of the compound of formula (3) is not reacted because there is a problem that the compound of formula (5) enters too much in the next step is generated a lot of the above-described side reactions.

In step a), the compound of Chemical Formula 4, which is not substituted with Chemical Formula 2, is produced. The compound of Chemical Formula 4 thus produced is included in the final material, causing problems such as lowering of crystallinity and lowering purity. The compound of Formula 5 is added to the compound to replace the compound of Formula 6. In this case, when the compound of Formula 5 is 1.5 equivalent or more with respect to the compound of Formula 4, the remaining compound of Formula 5 is increased, and the cyanuric acid is by-produced by hydrolysis, thereby producing a by-product. This happens. In addition, since the compound of Formula 4 remains below 1 equivalent, the compound of Formula 5 is preferably added in an amount of 1 to 1.5 equivalents based on the compound of Formula 4.

The compound of formula 7 is added to the compound of formula 6 to form the compound of formula 1, and the remaining traces of the compound of formula 5 and the compound of formula 7 are separated and purified to obtain the desired compound of formula 1 Get

Each of the above steps is characterized in that the successive.

The compound of Formula 1 produced as described above may be substituted with morpholine to obtain a compound of Formula 8.

[X of Formula 8 is the same as defined in Formula 1]

Cyano, nitro, amino, mono- or di (C ₁ -C ₇ ) alkyl amino, (C ₃ -C ₇ ) cycloalkylamino, morpholin oxide, piperazine, pipepe in addition to morpholine in the compound of Formula 8 Razine oxide, guanidine, urea and the like can be used.

As described above, since the impurity in which both of the amine groups of the compound of Formula 3 are substituted by only one amine group is minimized according to the present invention, high economic and industrial benefits can be obtained by omitting unnecessary processes used for purifying impurities. In addition, it showed an excellent effect on the increase of crystallinity and purity of the final material.

Hereinafter, the present invention will be described in more detail with reference to the manufacturing process according to the present invention. However, the present invention is not limited to the following examples.

LC (liquid chromatography) used in the embodiment of the present invention was used Agilent's 1100 Series, the column was Luna C18, the developing solvent using distilled water and Acetonitrile mixed solution, was measured under UV 254nm conditions. NMR used Bruker's 500MHz DRX500 model and IR used Scinco's Nicolet380. In addition, since this embodiment is a continuous process, NMR and IR analysis described only Example 2 and the final material.

[ Example  One] Benzene sulfonic acid , 2,2`- (1,2- Etondiil ) Vis [5-amino]- Disodium salt

After adding 615 ml of cooling water to Reactor-1 at room temperature, 122.23 g (0.5eq., LC Area: 95%) of 4,4'-diamino-2,2'-stilbenesulfonic acid (DAS) was slowly added. And stir. At this time, the reactants are in an emulsion state. Maintaining the stirring speed of the reactor-1 at about 70 rpm and adding 28.06 g of NaOH at room temperature, the 4,4'-diamino-2,2'-stilbendisulfonic acid is completely dissolved to give a clear dark brown color. The prepared benzenesulfonic acid, 2,2`- (1,2-ethendiyl) bis [5-amino] -disodium salt reaction solution is placed in a clean reactor-2. The inside of Reactor-1 is washed with clean water. The washed water is placed in reactor-2. Then used immediately for the next step.

[ Example  2] 4-amino-4,6- Dichloro -1,3,5- Triazine

After 105.8 ml of methyl ethyl ketone was added to Reactor-1, 121.7 g (1.0 eq, purity: 99%) of cyanuric chloride was added thereto, followed by stirring while maintaining the temperature inside the reactor at −5 ^° C. At this time, the reaction solution is in an emulsion state. 88.6 ml (1.1eq) of 28% NH ₄ OH aqueous solution was slowly added to the reaction of Reactor-1 over 20 minutes. At this time, as the reaction proceeds acidic as the reaction proceeds, it is maintained at pH 7 or higher by adding 87 g of 23% Na ₂ CO ₃ aqueous solution. At this time, the reaction is exothermic and the temperature inside the reaction is maintained at 0 ^o C. One hour after completion of the addition of the reactants, the reaction solution is sampled and subjected to structural analysis of 4-amino-4,6-dichloro-1,3,5-triazine (ADT).

¹ H NMR (500MHz, DMSO / TMS): δ 8.56 (s, 2H)

¹³ C NMR (500 MHz, DMSO / TMS): δ 167.32, 169.55

IR (KBr / Film, Cm ^-1 ): 3393, 3210, 2895, 2748, 1734, 1684, 1653, 1541, 1507,1419, 1344, 1319, 1256, 1214, 1077, 1014, 898, 850, 799, 747 , 686, 584, 531

[ Example  3] Benzene sulfonic acid , 2,2`- (1,2- Etondiil ) Vis [5- (4-amino-6- Chloro -1,3,5-triazin-2-yl) amino]- Disodium salt

The reaction solution of Reactor-2 was slowly added to Reactor-1 over 2 hours, and 158 g of 23% Na ₂ CO ₃ aqueous solution was added at the same time to maintain pH at 7 or more. At this time, the reaction is exothermic and maintains the internal temperature at room temperature. After the reaction solution of Reactor-2 was added, the internal temperature was raised to 45 ^° C. and the content of the compound of Formula 1 was analyzed by LC at 30 min intervals. Int-2-half in the following table is a compound in which ADT is substituted only on one side of the compound of Formula 3.

TABLE 1 Hourly LC Analysis of Example 3.

[ Example  4] Benzene sulfonic acid , 2,2`- (1,2- Etondiil ) Vis [5- (4,6- Dichloro -1,3,5- Triazine -2-yl) amino]- Disodium salt  mixture

The mixed solution of Example 3 was kept at 10 ° C. or lower, and slowly added 1.10 g of cyanuric chloride (CNC), followed by addition of 1.34 g of 23% Na ₂ CO ₃ aqueous solution to maintain the pH at 7 or more. At this time, the reaction is exothermic and the internal temperature is maintained at 10 ° C or lower. Thereafter, the internal temperature was raised to 45 ° C. and the content was analyzed by LC at 30-minute intervals. Int-3 in Table 2 is a compound in which CNC is substituted for Int-2-half.

Table 2. Hourly LC Analysis of Example 4

[ Example  5] Benzene sulfonic acid , 2,2`- (1,2- Etondiil ) Vis [5- (4-amino-6- Chloro -1,3,5-triazin-2-yl) amino]- Disodium salt

The mixed solution of Example 4 was maintained at 10 ° C., and 0.55 g of 28% NH ₄ OH aqueous solution was added thereto, and then 1.34 g of 23% Na ₂ CO ₃ aqueous solution was added to maintain the pH at 7 or more. At this time, the reaction is exothermic and the internal temperature is maintained at 10 ° C or lower. Thereafter, the internal temperature was raised to 45 ° C. and the content was analyzed by LC at 30-minute intervals.

Table 3. Hourly LC Analysis of Example 5

[ Example  6] Benzene sulfonic acid , 2,2`- (1,2- Etondiil ) Vis [5- [4-amino-6- (4- Morpholinyl ) -1,3,5- Triazine -2-yl] amino]- Disodium salt

Methyl ethyl ketone inside Reactor-1 is initially distilled under atmospheric pressure at 80 ° C. and distilled under vacuum (90 torr.). At this time, methyl ethyl ketone and a small amount of water are distilled together. 60.8 g of Morphine was then added over 10 minutes at 45 ^° C. and 346 g of 23% Na ₂ CO ₃ solution was added to maintain pH 8.8-9.2. The reaction temperature is maintained at 70 ^° C. for 2 hours while maintaining the temperature. At this time, the content of the final compound is analyzed by LC every 30 minutes. Then, the internal temperature of Reactor-1 is cooled to about 5 ^o C and filtered using a Nuche filter. The filtrate was dried in vacuo at 80 ^° C. to give 252.03 g of final compound. Analyze the purity and yield of the final compound.

Purity of Morpholin Substitute: 97.2%

Yield of morpholine substituent: 99.4%

¹ H NMR (500 MHz, D ₂ O / TMS): δ 7.23 (s.1H), 7.45 (d.1H), 7.61 (s.1H), 8.18 (s.1H)

IR (KBr / Film, Cm ^-1 ): 3363, 2862, 1615, 1539, 1506, 1448, 1407, 1306, 1284, 1223, 1183, 1108, 1081, 1022, 888, 834, 806, 700, 631, 541

Claims (11)

In the method for producing a compound represented by the following formula (1), a) reacting a compound of Formula 2 with a compound of Formula 3 to produce a mixture of Formula 1 and Formula 4; b) adding a compound of Formula 5 to the mixture produced in step a) to produce a mixture of Formula 1 and Formula 6; c) adding a compound of Formula 7 to the mixture produced in step b) to produce a compound of Formula 1; And d) separating and purifying to obtain a final compound (Formula 1); Method for producing sodium benzene sulfonate salt comprising a. [Formula 1]

[Formula 2]

[Formula 3]

[Formula 4]

[Formula 5]

[Formula 6]

[Formula 7]

[X is a straight or branched saturated or unsaturated (C ₁ -C ₁₀ ) alkyl, (C ₁ -C ₇ ) alkoxy, (C ₁ -C ₇ ) alkoxy (C ₁ -C ₇ ) alkyl, (C _1- C ₇ ) alkoxycarbonyl, (C ₁ -C ₇ ) alkoxycarbonyl (C ₁ -C ₇ ) alkoxy, (C ₁ -C ₇ ) alkoxycarbonyl (C ₁ -C ₇ ) alkylamino, (C _1- C ₇₎ alkoxycarbonyl (C ₁ - C ₇₎ alkyl, aminocarbonyl, (C ₁ - C ₇₎ alkylcarbonyloxy (C ₁ -C ₇₎ alkoxycarbonyl, hydroxy, cyano, nitro, amino, Mono or di (C ₁ -C ₇ ) alkylamino, mono or di (C ₁ -C ₇ ) alkylaminocarbonyl, mono or dibenzylamino, mono or di (C ₁ -C ₇ ) alkylamino (C _1- C ₇ ) _{3 to 7 comprising} at least one alkoxy, (C ₃ -C ₇ ) cycloalkylamino, (C ₁ -C ₇ ) alkylcarbonylamino, aminocarbonyl, oxygen, nitrogen or sulfur in the heterocycle Unsubstituted or substituted saturated or unsaturated heterocycloalkyl, mono or di halogen (C _1- C ₇ ) alkylsulfonamino, morpholin, morpholin oxide, piperazine, piperazine oxide, guanidine, (C ₁ -C ₇ ) alkylguanidine, urea, (C ₁ -C ₇ ) alkylurea, phenyl , Phenoxy, benzyl, benzyloxy, thiobenzyl, carboxylic acid, carboxyl (C ₁ -C ₁₀ ) alkylamino, carboxyl (C ₁ -C ₁₀ ) alkylaminocarbonyl, (C ₁ -C ₇ ) alkyl Ketones, and benzoyl]. The method of claim 1, X is nitro, amino, mono or di (C ₁ -C ₇ ) alkylamino, mono or di (C ₁ -C ₇ ) alkylaminocarbonyl, mono or dibenzylamino, mono or di (C ₁ -C ₇ ) Alkylamino (C ₁ -C ₇ ) alkoxy, (C ₃ -C ₇ ) cycloalkylamino, (C ₁ -C ₇ ) alkylcarbonylamino, and unsubstituted mono or di halogen (C ₁ -C ₇ A method for producing sodium benzene sulfonate salt, characterized in that the alkyl sulfonamino. The method of claim 2, X is a method for producing sodium benzene sulfonate salt, characterized in that amino. The method of claim 1, Formula (2) of step a) is a method for producing sodium benzene sulfonate salt, characterized in that the reaction with 1 to 2 equivalents relative to the formula (3). The method of claim 1, Formula 5 of step b) is a method for producing sodium benzene sulfonate salt, characterized in that 1 to 1.5 equivalents to react with the formula (4) of step a). a) reacting the compound of Formula 2 with the compound of Formula 3 to produce a mixture of Formula 1 and Formula 4; b) adding a compound of Formula 5 to the mixture produced in step a) to produce a mixture of Formula 1 and Formula 6; c) adding the compound of Formula 7 to the mixture produced in step b) to produce the compound of Formula 1; d) purification to obtain the compound of Chemical Formula 1; And e) adding a morpholine (Molpholine) to the compound of Formula 1 produced in step d) to generate the formula (8); Method for producing sodium benzene sulfonate salt, characterized in that. [Formula 8]

[X of Formula 8 is the same as defined in Formula 1] The method of claim 6, X is nitro, amino, mono or di (C ₁ -C ₇ ) alkylamino, mono or di (C ₁ -C ₇ ) alkylaminocarbonyl, mono or dibenzylamino, mono or di (C ₁ -C ₇ ) Alkylamino (C ₁ -C ₇ ) alkoxy, (C ₃ -C ₇ ) cycloalkylamino, (C ₁ -C ₇ ) alkylcarbonylamino, and unsubstituted mono or di halogen (C ₁ -C ₇ A method for producing sodium benzene sulfonate salt, characterized in that the alkyl sulfonamino. The method of claim 7, wherein X is a method for producing sodium benzene sulfonate salt, characterized in that amino. The method of claim 6, Formula (2) of step a) is a method for producing sodium benzene sulfonate salt, characterized in that the reaction with 1 to 2 equivalents relative to the formula (3). The method of claim 6, Formula 5 of step b) is a method for producing sodium benzene sulfonate salt, characterized in that 1 to 1.5 equivalents to react with the formula (4) of step a). The method according to any one of claims 1 to 10, Each step is carried out continuously, the method for producing sodium benzene sulfonate salt.