JPH09151162A - Purification of naphthalenedicarboxylic acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a purified product of high purity in a simple step when purifying crude naphthalenedicarboxylic acid. SOLUTION: Crude naphthalenedicarboxylic acid is dissolved in water at a high temperature under a high pressure and hydrogen is then reacted therewith in the presence of a noble metallic catalyst such as platinum to carry out the catalytic reducing treatment. The naphthalenedicarboxylic acid undergoing the catalytic reducing treatment is then crystallized and the resultant crystal is washed with a lower aliphatic carboxylic acid, typically warmed acetic acid.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a method for purifying crude naphthalenedicarboxylic acid obtained by oxidizing a substituent of a naphthalene compound having an alkyl substituent or a partially oxidized alkyl substituent.

[0002]

BACKGROUND OF THE INVENTION Naphthalenedicarboxylic acid, especially 2,6
-Naphthalenedicarboxylic acid is a compound useful as a raw material for highly functional resins such as polyethylene naphthalate (PEN).

As a method for producing 2,6-naphthalenedicarboxylic acid, a liquid phase oxidation method of 2,6-dimethylnaphthalene (for example, JP-A-6-172260) has been conventionally known. However, the naphthalenedicarboxylic acid produced by such a method contains impurities such as 6-formyl-2-naphthoic acid (abbreviated as "6-F-2-NA"). Even if a small amount of such impurities, the polyester produced by polycondensation of 2,6-naphthalenedicarboxylic acid and ethylene glycol is colored and the degree of polymerization is lowered, resulting in a quality defect.

Therefore, 2, including the above-mentioned impurities,
Purification of 6-naphthalenedicarboxylic acid is an important issue, and many solutions have been proposed so far. For example, low-purity 2,6-naphthalenedicarboxylic acid obtained by liquid-phase oxidation was esterified with methanol (Japanese Patent Laid-Open No. Sho 5).
0-95253), followed by distillation (Japanese Patent Publication No. 50-29291) or recrystallization (Japanese Patent Laid-Open No. 50-111056) to highly purify 2,6-naphthalenedicarboxylic acid dimethyl ester. There is. Crude 2,6-naphthalenedicarboxylic acid is dissolved in an alkaline aqueous solution and then decolorized (Japanese Patent Publication Nos. 52-20993 and 52-2099).
4, JP-A-49-133359 and JP-A-50-10563.
9, the same 62-212341, the same 62-212342),
Oxidizing treatment (JP-A-48-68554 and 48-68)
555, JP-A-2-250849) or a hydrogenation treatment (Japanese Patent Publication No. 57-36901).
There is also a method (US Pat. No. 5,256,817) in which a hydrogenated refining method established as a method for producing high-purity terephthalic acid is applied to naphthalenedicarboxylic acid.

Among the above-mentioned purification techniques, the method of advancing the purification in the form of methyl ester requires an esterification reaction between carboxylic acid and methanol prior to the purification, which complicates the process and of course costs too. Get higher
Since other refining methods also use alkalis and acids, they require steps of acid precipitation and neutralization, which are also economically disadvantageous. Since the hydrogenation purification method uses a mixed solvent of a lower aliphatic carboxylic acid and water as a solvent, a step of separating and recovering the solvents after the reaction is required. Further, since the solubility of naphthalenedicarboxylic acid in the lower aliphatic carboxylic acid aqueous solution, which is a solvent, is low, a large amount of solvent is required.

[0006]

SUMMARY OF THE INVENTION The object of the present invention is to solve the above-mentioned drawbacks associated with conventional methods for purifying naphthalenedicarboxylic acid, to simplify the process, and to provide economically highly pure naphthalenedicarboxylic acid. It is to provide a purification method capable of obtaining

[0007]

The method for purifying naphthalenedicarboxylic acid according to the present invention is a crude product obtained by oxidizing a substituent of a naphthalene compound having an alkyl substituent or a partially oxidized alkyl substituent. In the method for purifying naphthalenedicarboxylic acid, crude naphthalenedicarboxylic acid is dissolved in water under high temperature and high pressure, and reduction treatment is carried out by reacting hydrogen in the presence of a hydrogenation catalyst, followed by washing with a lower aliphatic carboxylic acid. It is characterized by doing.

The crude naphthalenedicarboxylic acid to which the purification method of the present invention can be applied is obtained by oxidizing a substituent of a naphthalene compound having an alkyl substituent or a partially oxidized alkyl substituent as described above. A typical example of the alkyl substituent is a lower alkyl group having 1 to 3 carbon atoms such as methyl, ethyl, propyl, isopropyl and the like. Examples of the partially oxidized alkyl substituent include oxygen-containing hydrocarbon groups other than the carboxyl group such as an aldehyde group and a hydroxyalkyl group.

Such crude naphthalene dicarboxylic acid is obtained by completely or partially oxidizing a dialkylnaphthalene or its substituted alkyl group (up to a carboxyl group) or incompletely, and using this as a starting material. Any material can be used as long as it is obtained by oxidation. Specific examples of the starting material include 2,6-dimethylnaphthalene, 2,7-dimethylnaphthalene, 1,2-dimethylnaphthalene and 1,3-
Dimethylnaphthalene, 1,4-dimethylnaphthalene,
1,5-dimethylnaphthalene, 1,6-dimethylnaphthalene, 1,7-dimethylnaphthalene, 1,8-dimethylnaphthalene, 2,3-dimethylnaphthalene, 2,6-diethylnaphthalene, 2,7-diethylnaphthalene, 2 ，
6-diisopropylnaphthalene, 2,7-diisopropylnaphthalene, 6-acetyl-2-methylnaphthalene,
6-formyl-2-methylnaphthalene, 4-hydroxymethyl-1-methylnaphthalene, 6-methyl-2-naphthoic acid and the like can be mentioned.

The products of the oxidation reaction of these starting materials, which are suitable for purification according to the present invention, include a lower aliphatic carboxylic acid as a reaction medium, cobalt, manganese, and
It is a crude product of naphthalene dicarboxylic acid obtained by liquid-phase oxidation with molecular oxygen using a catalyst such as bromine. Examples of such a crude product include a crude naphthalene dicarboxylic acid prepared by the production method described in JP-A-6-172260. In the method for producing naphthalenedicarboxylic acid of JP-A-6-172260, methylnaphthalene is added in an amount of 5 to 3
Dissolved in 8 times the amount of lower aliphatic carboxylic acid, as a catalyst,
Co, Mn and Br are each used in a specific amount with respect to a lower aliphatic carboxylic acid, and methylnaphthalene (having 1 to 4 methyl groups) is oxidized with molecular oxygen.

The reaction medium used in the present invention is water as described above. For example, the use of water such as distilled water or ion-exchanged water is sufficient. The amount of water used as the reaction medium is such that the crude naphthalene dicarboxylic acid is at least partially, preferably completely dissolved at the reaction temperature. Usually, 2 to 20 times the weight of the crude product is used. Particularly, the amount of 3 to 10 times is preferable. If the amount of the reaction medium is too small, needless to say, the amount of the crude naphthalenedicarboxylic acid dissolved will be small, and purification by hydrogeno-reduction will not be sufficiently carried out. If the amount is too large, there is no problem in the reaction, but a large reactor is required, and the energy consumption required for recovery of naphthalenedicarboxylic acid increases, which is economically disadvantageous.

The reaction temperature is the temperature at which the crude naphthalene dicarboxylic acid is sufficiently dissolved in the reaction medium. At low temperatures the solubility is low and large amounts of solvent are required. If the temperature is too high, an undesired decomposition reaction such as cleavage of the naphthalene ring or elimination of the carboxyl group occurs. A preferable temperature is 250 to 330 ° C, and a particularly preferable temperature is 280 to 310 ° C.

The hydrogen reduction treatment of the present invention is carried out using hydrogen gas and a hydrogenation catalyst. The partial pressure of hydrogen is 0.01
-6 MPa is suitable, and 0.5-2 MPa is preferable. The overall pressure of the reaction system is such that at least part of the reaction medium can be present in liquid form. It is preferable that 50 mass% or more is present in the liquid phase portion, and it is particularly preferable that it is present in an amount of about 75 mass%. The pressure cannot be generally specified because it is influenced by the temperature of the system, the hydrogen partial pressure, and the type and amount of the reaction medium, but it is usually 3 to 13 MPa, and the preferable range is 5
10 MPa.

The metal catalyst used as the hydrogenation catalyst is, as described above, a noble metal of Group VIII of the Periodic Table, namely palladium, rhodium, ruthenium, osmium, iridium,
And one or more of platinum. This catalyst hydrogenates formylnaphthoic acid and brominated naphthalenedicarboxylic acid, which are impurities in crude naphthalenedicarboxylic acid, and converts them into compounds that can be easily separated from naphthalenedicarboxylic acid, and also converts colored components into colorless compounds. To do. Highly effective catalysts are platinum, palladium, rhodium and ruthenium. The catalyst may be used in the form of powder or granules, or may be used by supporting it on a carrier.
As the carrier, activated carbon, graphite, alumina, zeolite, silica or the like can be used, but activated carbon is particularly preferable. The supported amount is suitably 0.1 to 5 mass% based on the total amount of catalyst. The amount of the catalyst used is determined by the reaction temperature, the concentration of impurities in the crude naphthalenedicarboxylic acid, the residence time in the reactor, and other conditions, but in general, the crude naphthalenedicarboxylic acid for the noble metal component in the hydrogenation catalyst is The mass ratio may be about 200: 1 to about 30,000: 1, preferably about 2,000: 1 to about 20,000: 1. When the amount of precious metal catalyst is small, the hydrogenation reaction rate of impurities remains at a low value. On the other hand, the presence of an excessive amount of catalyst undesirably promotes the decarbonylation reaction of naphthalenedicarboxylic acid and the nuclear hydrogenation reaction of the naphthalene ring. .

The reaction time depends on the amount ratio of the crude naphthalene dicarboxylic acid to the hydrogenation catalyst, the hydrogen concentration and the reaction temperature. As a measure of actual operation, the residence time during which the reaction mixture is in contact with the hydrogenation catalyst or the feed weight rate (W
HSV), it is about 200 to 200,000 g (reaction solution) / g (noble metal component in the hydrogenation catalyst) · hr, preferably 1,000 to 100,000 g / g · hr.
The reaction system is not limited, and a continuous system or a batch system can be arbitrarily selected.

After the completion of the catalytic reduction treatment, the hydrogenation catalyst existing as a solid in the reaction medium and the naphthalenedicarboxylic acid dissolved in the aqueous medium are separated.

Generally, naphthalenedicarboxylic acid is hardly soluble or almost insoluble in water under normal temperature and normal pressure, but its solubility in the reaction medium increases under high temperature and high pressure. Therefore, it can be dissolved or filtered by a means such as centrifugation. It can be taken out by solid-liquid separation of the hydrogenation catalyst and the reaction product liquid. The conditions of high temperature and high pressure at which naphthalenedicarboxylic acid is easily dissolved in an aqueous reaction medium are a temperature of 250 ° C. or higher and a pressure of 3 MPa or higher. Under these conditions, the solubility of naphthalenedicarboxylic acid in water is at least about 10% by mass. is there. The practical limits are a temperature of 330 ° C and a pressure of 1.
It is 0 MPa. A suitable range is a temperature of 280 to 310 ° C. and a pressure of 7 to 10 MPa.

The reaction may be carried out continuously or in a batch operation. If the reaction is carried out by a continuous method in which the catalyst is used as a fixed bed and the reaction solution is passed therethrough, solid-liquid separation between the catalyst and the reaction solution can be carried out.

Following the solid-liquid separation, the obtained reaction product liquid is cooled to crystallize naphthalenedicarboxylic acid. The crystallization temperature is between 250 ° C and 30 ° C. 100-35 degreeC is preferable. At this time, the cooling rate is preferably 25 ° C / min or less, more preferably 1
Set to 0 ° C / min or less. If the cooling rate is too fast, the precipitated particles of naphthalene dicarboxylic acid will become extremely fine,
Separation from mother liquor becomes difficult. The purified naphthalene dicarboxylic acid that has precipitated is collected by means such as filtration and centrifugation.

The naphthalenedicarboxylic acid obtained by the above operation is mixed with methylnaphthoic acid and naphthoic acid produced by the catalytic reduction treatment. Methylnaphthoic acid and naphthoic acid are those produced by reduction of an oxidizing intermediate such as formylnaphthoic acid contained in crude naphthalene dicarboxylic acid with hydrogen, and the solubility of these compounds in an aqueous solvent is naphthalene. It is as low as dicarboxylic acid and extremely low. Therefore, after catalytic reduction treatment, solid-liquid separation with a hydrogenation catalyst is performed, and the reaction solution is cooled to around room temperature to precipitate naphthalenedicarboxylic acid. Mix in acid. Therefore, by washing the naphthalenedicarboxylic acid with a lower aliphatic carboxylic acid following the catalytic reduction treatment,
Methylnaphthoic acid and naphthoic acid can be removed.

The washing with the lower aliphatic carboxylic acid is carried out by pouring the heated lower aliphatic carboxylic acid from above the solid layer, followed by filtration and washing (rinsing), and after making the solid and the lower aliphatic carboxylic acid into a uniform slurry. Both filtering methods (reslurries) are included. The simplest method is the former method, but the effective method is the latter method. It can be used properly according to the content of impurities. here,
Lower aliphatic carboxylic acid used is an aliphatic carboxylic acid C ₂ -C _6, particularly acetic acid is preferred. The amount of lower aliphatic carboxylic acid used is determined by conditions such as the concentration of methylnaphthoic acid and naphthoic acid contained in naphthalenedicarboxylic acid, the washing time, the temperature of the lower aliphatic carboxylic acid at the time of washing, and the like. The amount may be sufficient to completely dissolve the mixed methylnaphthoic acid and naphthoic acid. Generally, the lower aliphatic carboxylic acid used relative to the naphthalene dicarboxylic acid is about 2-1 by weight.
It is preferably 00 times, particularly 3 to 50 times, and more preferably 5 to 20 times.

The washing temperature may be above the temperature at which the impurities methylnaphthoic acid and naphthoic acid are completely dissolved in the used amount of lower aliphatic carboxylic acid. In general,
25 to 90 ° C. in the case of rinsing among the cleaning methods described above,
It is preferably 40 to 80 ° C., and 2 in the case of reslurry.
It is 5 to 115 ° C, preferably 40 to 100 ° C. If the washing temperature is low, the solubility of methylnaphthoic acid and naphthoic acid cannot be sufficiently obtained, and the purity of naphthalenedicarboxylic acid cannot be improved. On the other hand, if the temperature is too high, the amount of naphthalenedicarboxylic acid dissolved in the lower aliphatic carboxylic acid, which is a washing solvent, increases, and the naphthalenedicarboxylic acid loss due to washing increases, which is not preferable.

Although the cleaning time varies depending on the cleaning method,
Generally, when rinsing is performed as a washing method, it depends on the filtration rate, but generally 5 to 30 minutes, preferably 10 to
It is 30 minutes, and in the case of reslurry, it is 5 to 60 minutes, preferably 10 to 30 minutes.

The thus-obtained naphthalenedicarboxylic acid has very little inclusion of impurities and is highly pure, and can be used as a raw material for polyester resins.

[0025]

EXAMPLES In the following examples, the purity was measured by high performance liquid chromatography (HPLC), analytical column: Asahipak ODP-50 (Shodex), solvent: 10 mM.
-NaH was performed using ₂ PO ₄ + _5mM- tetrabutylammonium bromide (pH 7.5) aqueous solution / acetonitrile. Regarding the hue, the L value (brightness), a value [red (+) to green (-)], and b value [yellow (+) to blue] of a powder sample prepared and packed in a cylindrical glass cell. (-)] Was calculated. The closer the L value is to 100 and the closer the a value and the b value are to 0, the closer it is to white.

Example 1 According to the method described in JP-A-6-172260, 2,6-dimethylnaphthalene was oxidized to produce crude naphthalenedicarboxylic acid. The crude 2,6-naphthalenedicarboxylic acid obtained has a purity of 9
1% of 6-F-2-NA as an impurity at 8.8% by mass
2,000ppm, and the hue is [L90, a-4, b1
2].

The crude naphthalenedicarboxylic acid was purified using the experimental apparatus shown in FIG. This device is provided with a heater and a heat insulating material (not shown), and the temperature is accurately controlled by a temperature controller.

First, 120 g of the crude 2,6-naphthalenedicarboxylic acid was added to a titanium reaction tank (1) having a condenser (11) and a gas blowing pipe (12) at the top and equipped with a stirrer (13). 25.2 g of 0.5% palladium activated carbon catalyst and 600 g of water were charged. Open the valve (3) and add 0.9 hydrogen from the gas injection pipe (12).
Nl was injected. While stirring with the stirrer (13), the reaction tank was heated with the heater (2) to raise the temperature. After the temperature in the reaction tank reached 310 ° C. and the pressure reached 9.0 MPa, the reaction was continued for 30 minutes.

After completion of the reaction, the valve (5) was opened while keeping the temperature, and the reaction mixture was mixed with the sintered metal filter (4).
Through a solid-liquid separation into a catalyst and a reaction product liquid, and the liquid was transferred to a cooling tank (6) provided with a condenser (61) through an introduction pipe (62).

Up to 40 ° C., the mixture was cooled at a cooling rate of 20 ° C./min to crystallize purified 2,6-naphthalenedicarboxylic acid. After lowering the internal pressure of the cooling tank (6) to normal pressure, the valve (7) was opened to collect a slurry containing purified 2,6-naphthalenedicarboxylic acid.

The slurry was filtered under reduced pressure to separate the solid from the mother liquor. Then, from the top of the filtration case, 80
600 g of acetic acid heated to 0 ° C. was poured and filtered while washing. Finally, 120 g of water was poured, washed and filtered.

When the solid was dried and the purity was measured, it was 99.98% by mass or more, the 6-F-2-NA content was 100 ppm or less, 2-naphthoic acid (hereinafter, referred to as "2-
(Abbreviated as "NA") content was 100 ppm or less.
The hue was also improved to [L 95, a -1.7, b 0.5].

Example 2 Using the same apparatus as in Example 1, the crude 2,6-naphthalenedicarboxylic acid produced in the same manner as in Example 1 was catalytically reduced under the same conditions as in Example 1.
After completion of the reaction, 2,6-naphthalenedicarboxylic acid recovered by vacuum filtration was transferred to a 2-liter eggplant flask, 800 g of acetic acid was placed therein, and a condenser was attached.
While stirring with a magnetic stirrer, the temperature was raised to 110 ° C. and the temperature was maintained for 30 minutes. Then, it cooled to 60 degreeC and filtered. Finally, 120 g of water was poured, washed, and filtered. When the solid was dried and the purity was measured, it was 99.98% by mass or more. 6-F-2-
NA content 100ppm or less. 6-Methyl-2-2naphthoic acid (hereinafter abbreviated as "6-M-2-NA") and 2-NA content 100 ppm or less. The hue is also [L 96,
a-1.5, b 0.7].

Example 3 Using the same apparatus as in Example 1, the crude 2,6-naphthalenedicarboxylic acid produced in the same manner as in Example 1 was catalytically reduced under the same conditions as in Example 1.
After completion of the reaction, 2,6-naphthalenedicarboxylic acid recovered by vacuum filtration was charged into a 1.5-liter titanium autoclave. 500 g of acetic acid was charged therein, and the air in the system was replaced with nitrogen. While stirring with a stirrer, the reaction tank was heated with a heater to raise the temperature. After the temperature in the reaction tank reached 300 ° C and the pressure reached 43 MPa, 3
Hold for 0 minutes. Then, after cooling to 40 ° C., the autoclave is opened, the slurry is taken out and filtered under reduced pressure,
Solid 2,6-naphthalenedicarboxylic acid and acetic acid solvent were separated. Finally, 120 g of water was poured into the solid layer and filtered. When the purity was measured after drying the solid, it was 99.98 mass% or more (6-F-2-NA content 1
00 ppm or less, 6-M-2-NA and 2-NA content 100 ppm or less), and the hue is [L 95, a -1.2,
b 0.9].

Example 4 Crude 2,7-naphthalenedicarboxylic acid was produced by oxidizing 2,7-dimethylnaphthalene according to the method described in JP-A-6-172260.
The obtained crude 2,7-naphthalenedicarboxylic acid had a purity of 98.8% by mass, contained 12,000 ppm of 7-F-2-NA as an impurity, and had a hue of [L 90, a -3.
2, b 11].

The above-mentioned crude 2,7-naphthalenedicarboxylic acid was purified using the experimental apparatus shown in FIG.
In the reaction tank, the crude 2,7-naphthalenedicarboxylic acid 1
20 g, 0.5% palladium on activated carbon 25.2 g and water 600 g were charged. Subsequently, 0.9 Nl of hydrogen was injected. The reaction tank was heated with stirring to raise the temperature. After the temperature in the reactor reaches 310 ° C and the pressure reaches 9.0 MPa,
The reaction was continued for 30 minutes.

After completion of the reaction, the reaction mixture was subjected to solid-liquid separation into a catalyst and a reaction product solution through a sintered metal filter while maintaining the temperature, and the solution was transferred to a cooling tank.

The crude 2,7-naphthalenedicarboxylic acid was crystallized by cooling to 40 ° C. at a cooling rate of 20 ° C./min. After reducing the internal pressure of the cooling tank to atmospheric pressure, refine the product 2,7
-A slurry containing naphthalenedicarboxylic acid was collected.

The slurry was filtered under reduced pressure to separate the solid from the mother liquor. Subsequently, 600 g of acetic acid heated to 80 ° C. was poured from above the solid layer and filtered. Finally water 12
0 g was poured, washed and filtered. When the purity was measured after drying the solid, it was 99.98% by mass or more (7-F
-2-NA content 100 ppm or less, 7-M-2-NA and 2-NA content 100 ppm or less), and the hue is [L 9
6, a-1.9, b0.7].

Comparative Example 1 Using the same apparatus as in Example 1, the crude 2,6-naphthalenedicarboxylic acid produced in the same manner as in Example 1 was catalytically reduced under the same conditions as in Example 1.
After completion of the reaction, the purity of 2,6-naphthalenedicarboxylic acid recovered by vacuum filtration was measured without drying, and the purity was measured to be 99.3 mass% (6-F-2-NA content 100 ppm or less, 6- M-2-NA and 2-NA
Content was 7,000 ppm).

Comparative Example 2 Using the same apparatus as in Example 1, the crude 2,6-naphthalenedicarboxylic acid produced in the same manner as in Example 1 was catalytically reduced under the same conditions as in Example 1.
After the reaction was completed, 100 g of acetic acid heated to 80 ° C. was poured over the 2,6-naphthalenedicarboxylic acid recovered by vacuum filtration, washed, and filtered. Finally, 120 g of water was poured and the mixture was filtered and washed. When the purity was measured after drying the solid, it was 99.5 mass% (6-F-2
-NA content was 100 ppm or less, 6-M-2-NA and 2-NA content was 5000 ppm). Since the amount of hot acetic acid used for washing was small, the purification effect was not high.

Comparative Example 3 Using the same apparatus as in Example 1, the crude 2,6-naphthalenedicarboxylic acid produced in the same manner as in Example 1 was catalytically reduced under the same conditions as in Example 1.
After completion of the reaction, 600 g of acetic acid warmed to 25 ° C. was poured over the 2,6-naphthalenedicarboxylic acid recovered by vacuum filtration, washed, and filtered. Finally water 1
20 g was poured and the mixture was filtered and washed. When the purity was measured after drying the solid, it was 99.3% by mass (6-F-2-
NA content 100ppm or less, 6-M-2-NA and 2
-NA content was 7,000 ppm). Since the heating temperature of acetic acid was low, the purification effect was low.

[0043]

Industrial Applicability According to the method of the present invention, crude naphthalene dicarboxylic acid obtained by oxidation of dialkylnaphthalene is effectively purified by a simple process of reduction treatment with hydrogen and washing with lower aliphatic carboxylic acid. A high-purity product can be obtained.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification number Reference number within the agency FI Technical indication location C07C 51/487 2115-4H C07C 51/487 (72) Inventor Mamoru Donomae Central 5 chome, Yamato City, Kanagawa Prefecture 2-26-502

Claims (1)

[Claims] 1. A method for purifying a crude naphthalenedicarboxylic acid obtained by oxidizing a substituent of a naphthalene compound having an alkyl substituent or a partially oxidized alkyl substituent, wherein the crude naphthalenedicarboxylic acid is treated at high temperature and high pressure. A method for purifying naphthalenedicarboxylic acid, which comprises dissolving in water under reduced pressure, reducing the treatment with hydrogen in the presence of a hydrogenation catalyst, and subsequently washing with a lower aliphatic carboxylic acid.