KR880001313B1 - Method for preparing tetrahydroindole derivative - Google Patents

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Description

Method for preparing tetrahydroindole derivative

로 표시되는 아드레노크롬 모노세미카바존(즉, 1-메틸-3-하이드록시-5-세미카바조노-6-옥소-2, 3, 5, 6-테트라하이드로인돌)에 대한 신규이고 효유적인 제조방법에 관한 것이다.The present invention is the following general formula,

Novel and effective against adrenochrome monosemicabazone (ie 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole) represented by It relates to a manufacturing method.

The compound (I) of the present invention is not only useful as a hemostatic agent, but also widely used as a hemostatic agent, carbazochrome sodiumsulfonate (i.e., 1-methyl-5-semicarbazono-6-oxo-2, 3, 5, 6-tetrahydroindole-2-sulfonic acid sodium salt) is also useful as an intermediate of the synthesis.

Several preparation methods for preparing the above compound (I) by oxidizing adrenergic with various oxidants and then treating with semicarbazide are known. Examples of the oxidizing agent include potassium ferricyanide (Journal of Chemical Society, P, 2248-2252, 1951), lead dioxide (Naeji, 166, P, 831-832, 1950), magnesium dioxide (Chemical Abtract, Vol. 4, 4533, 1950), Mercury Halide (Chemical Abtract) , 44, 2580, 1950), cericsulfate (Chemical Abtract, 42, 5075, 1948), Fenton's reagent (Journal of Baral Chemical Chemistry, 220, P, 227-235, 1956) , Diphenic selenoxide (synthesis, P, 172, 1973). However, these oxidation methods have the serious drawback of producing harmful by-products as industrial methods.

It is also known to oxidize adrenaline with sodium persulfate to yield no harmful byproducts (Journal of Chemical Society P, 1276-1282, 1950).

However, the above oxidation method has a defect in yield and purity of the product. Under these circumstances, the need for development of a manufacturing method for adrenochrome monosemicabazone (I), which is economical and of high purity, has been increased.

On the other hand, the method of synthesizing organic compounds using electrolysis using electrons as a reagent has recently attracted attention as a pure method that does not produce harmful by-products.

However, electrolysis generally requires a long time to complete the reaction and must be carried out under constant current or constant voltage.

Thus, since these materials are unstable under electrolysis conditions, the electrosynthesis method has been recognized as unsuitable for industrial production. Compound (I) is an intermediate, adrenochrome, which is very unstable in aqueous solution, and turns into a substance such as rutin or melanin within a few hours at room temperature, and is also easy to oxidize in aqueous solution.

Therefore, in preparing compound (I), no electrolysis method for oxidizing adrenergic to adrenochrome was used.

As a result of extensive research on the oxidation of adrenaline under such circumstances, the inventors of the present invention are stable as adrenochrome is in an aqueous solution containing a salt, and as a result, when electrolytic oxidation is carried out in water containing an auxiliary electrolyte, The present inventors have found that adrenaline is selectively oxidized without being excessively oxidized to adrenochrome, and thus, the present invention has been completed.

An object of the present invention is to adrenochrome (III), that is, by electrolytic oxidation of adrenaline (II) or 3, 4-dihydroxy-α-[(methylamino] methyl] benzin alcohol in water containing an auxiliary electrolyte Adrenochrome monosemicabazone formed by producing 1-methyl-3-hydroxy-5, 6-dioxo-2, 3, 5, 6-tetrahydroindole and reacting this with semicarbazide (IV) (I), i.e., a novel and efficient method for preparing 1-methyl-3-hydroxy-5-semicabanono-6-oxo-2, 3, 5, 6-tetrahydroindole.

The reaction according to the present invention is as follows.

The manufacturing method of the present invention will be described in more detail below.

In the first step of the present invention, the electrolytic oxidation is performed by adding an auxiliary electrolyte to both the catholyte and the anolyte or catholyte, using water as a solvent, and applying a current to an electrolytic cell installed so that the anode and the cathode are separated by a diaphragm such as an anion exchange membrane. It is done by feeding.

As the electrolyzer used in the present invention, various types of electrolyzers such as an H-type electrolyzer and a filter press-type electrolyzer may be used.

The electrolyzer should be made of a material that can withstand the action of the electrolyte. The electrolytic cell should be separated into the anode chamber and the cathode chamber by the diaphragm.

In industrial production, it is preferable to use a filter press type electrolytic cell in which a plurality of positive electrode plates and negative electrode plates are arranged in parallel to each other and a diaphragm is disposed between the positive electrode plates and the negative electrode plates. For example, a graphite electrode, a platinum electrode, a lead electrode, etc. can be used suitably as an anode used for the electrolytic oxidation of this invention, and a graphite electrode, a platinum electrode, a lead electrode, a stainless steel electrode etc. can be used suitably as a cathode.

Separation between the anode chamber and the cathode chamber is used such as an ion exchange membrane, a ceramic membrane, cellophane or sintered glass, and an anion exchange membrane is preferable.

Examples of the auxiliary electrolyte added to both the catholyte or the anolyte or to the cathode include sodium formate, potassium formate, sodium acetate, potassium acetate, lithium acetate, sodium propionate, potassium propionate, sodium citrate, potassium citrate and Alkali metal salts of the same organic compounds, lithium chloride, sodium chloride, potassium chloride, sodium sulfate, potassium sulfate, sodium hydrogen sulfate, potassium hydrogen sulfate, sodium hydrogen phosphate, sodium diahydrogen phosphate, potassium hydrogen phosphate, potassium di Alkali metal salts of inorganic compounds such as hydrogen phosphate, sodium borate, potassium borate, sodium perchlorate, potassium perchlorate, tetramethylammonium chloride, tetramethylammonium Silate, tetramethylammonium chloride, tetramethylammonium bromide, tetraethylammonium tosylate, tetraethylammonium perchlorate, tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium tosylate, tetrabutylammonium perchlorate, tetrabutylammonium tetrafluor There is a tertiary ammonium salt such as bororate.

The above secondary electrolytes are used alone or as a mixture.

Preferred above are alkali metal salts of organic compounds, more preferably sodium acetate.

The amount of auxiliary electrolyte is different in the anolyte and catholyte.

For example, when sodium acetate is used as the auxiliary electrolyte, an amount of 0-0.4 mole is suitable for 1 mole of adrenaline (II) in the anolyte, and preferably 0-0.5 mole.

When the filter press-type electrolytic cell mentioned above is used, addition of the auxiliary electrolyte to the anolyte is not essential because some components of the catholyte may enter the anolyte through the diaphragm.

On the other hand, the catholyte is preferably added at least 0.5 mol, preferably 0.5-60 mol, and more preferably 0.5-25 mol of the auxiliary electrolyte per mol of adrenaline (II).

The electrolytic oxidation is effective to be carried out in the presence of acid in the anolyte solution.

Examples of such acids include organic acids such as formic acid, acetic acid, propionic acid and citric acid, of which acetic acid is preferred.

Such acid is used in an amount of 0.1-10.0 moles, preferably 1.0-2.0 moles, per 1 mole of adrenaline (II).

In the electrolytic oxidation of the present invention, the anolyte which is an aqueous solution containing adrenaline (II), water and an auxiliary electrolyte which may be included if necessary, and the catholyte which is an aqueous solution containing water and an auxiliary electrolyte are respectively an anode chamber and an anode chamber in an electrolytic cell. Located in

Thereafter, a current is passed through the electrolyzer.

The concentration of adrenaline (II) in the anolyte is appropriately 0.5-3W / W%.

The density of the current to be supplied may be appropriately selected, but is preferably about 0.1-50 mA / cm 2.

The electrolytic oxidation is generally carried out at 0-20 占 폚, preferably 1-10 占 폚.

The reaction time depends on the amount of adrenaline (II) used, the amount of current supplied, and the like, but generally 10 hours or less is preferable.

In the electrolytic oxidation as described above, adrenochrome (III) is produced in the anolyte solution, and is treated in the next step without being separated.

The reaction of the adrenochrome (III) and the semicarbazide in the second step can be easily carried out by adding semicarbazide to the anolyte solution in which the electrolytic oxidation reaction is terminated.

It is effective to use the semicarbazide (IV) in the form of hydrochloride. Moreover, as for reaction temperature, 5-20 degreeC is preferable.

The resulting compound (I) is collected by adjusting the pH to 5.0-5.3 by adding an aqueous alkali solution (e.g., an aqueous sodium carbonate solution) or an acidic aqueous solution (e.g., 1N hydrochloric acid) to the reaction mixture, followed by filtration or The treatment is done in the usual way.

According to the production method of the present invention, no harmful substances or by-products are produced, and compound (I) having high purity in a good yield is produced, which is an excellent industrial production method for compound (I).

The manufacturing method of the present invention will be described in more detail with reference to the following examples.

However, this does not limit the present invention.

In addition, adrenochrome (III), an intermediate of the present invention, and adrenochrome monosemicabazone (I), a final product, may be represented in the form of zwitterion as follows.

However, in the present specification, as mentioned above, these compounds are named based on the structures of the general formulas (I) and (III).

Example 1

A mixture of 1.37 g of 3,4-dihydroxy-α-[(methylamino) methyl] benzyl alcohol (i.e., adrenaline), 2.04 g of sodium acetate and trihydrate, 1.72 ml of acetic acid and 137 ml of water was used as an anion exchange membrane. It was placed in the anode chamber in the electrolytic cell installed to be separated.

In addition, a mixture of 2.04 g of sodium acetate trihydrate and 137 ml of water was placed in a cathode chamber.

Graphite electrodes (4 x 5 cm 2) were placed in parallel in each anode chamber.

The electrolysis was carried out under vigorous stirring with a constant current of 102 mA at 1 ° C. until the total current reached 75% of the theoretical amount, followed by lowering the current to a constant current of 75 mA.

After passing the theoretical amount of current, semicarbazide is obtained by taking adrenochrome produced in the anolyte, namely, 1-methyl-3-hydroxy-5, 6-dioxo-2, 3, 5, and 6-tetrahydroindole. Mix with 1.0 g hydrochloride.

The mixture was adjusted to 5.2 with saturated sodium carbonate solution under vigorous stirring and stirred at 8 ° C. for one and a half hours.

The precipitated crystals were collected by filtration, washed with 10 ml of ice water, and then dried in vacuo to give 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetra as red crystals. Hydroindole (ie, adrenochrome monosemicabazone) was obtained. Yield: 1.30 g (74.4%)

NMR (d ₆ -DMSO) δ: 3.01 (s, 3H), 3.33-4.2 (m, 2H), 4.8-5.2 (m, 1H), 5.38 (s, 1H), 5.75 (d, 1H, J = 5Hz ), 6.72 (s, 1H), 7.02 (broad, 2H), 14.71 (broad, 1H)

Example 2

The reaction was carried out in the same manner as in Example 1, except that a platinum electrode (4 x 5 cm 2) was used instead of the graphite electrode.

1.19 g of 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole, which are red crystals, were obtained. Yield: 67.2%

The physicochemical properties of the product were the same as those of the material obtained in Example 1.

Example 3

The reaction was carried out in the same manner as in Example 1, except that the internal temperature of the anolyte solution was maintained at 5 ° C instead of 1 ° C.

1.20 g of 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole as red crystals were obtained. Yield: 72.9%

The physicochemical properties of the product were the same as those of the material obtained in Example 1.

Example 4

The reaction was carried out in the same manner as in Example 1, except that the internal temperature of the anolyte solution was maintained at 10 ° C instead of 1 ° C.

1.26 g of 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole as red crystals were obtained. Yield: 71.2%

The physicochemical properties of the product were the same as those of the material obtained in Example 1.

Example 5

The reaction was carried out in the same manner as in Example 1, except that 1.47 g of potassium acetate was used as the electrolyte instead of sodium acetate.

1.31 g of 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole, which are red crystals, were obtained. Yield: 74.0%

The physicochemical properties of the product were the same as those of the material obtained in Example 1.

Example 6

The reaction was carried out in the same manner as in Example 1, except that 1.02 g of sodium formate and 0.69 g of formic acid were used instead of sodium acetate and acetic acid as the electrolyte.

1.17 g of red crystals 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole were obtained. Yield: 66.1%

The physicochemical properties of the product were the same as those of the material obtained in Example 1.

Example 7

3,4-dihydroxy-α-[(methylamino) methyl] benzyl alcohol, 2.06 g, sodium acetate trihydrate 3.06 g, a mixture of 2.58 ml of acetic acid and 137 ml of water were installed so that the positive and negative electrodes were separated by an anion exchange membrane. It was placed in the anode chamber in the electrolytic cell.

A mixture of 3.06 g of sodium acetate trihydrate and 137 ml of water was placed in a cathode chamber.

Graphite electrodes (4 x 5 cm 2) were placed in parallel in each anode chamber.

The electrolysis was carried out under vigorous stirring with a constant current of 153 mA at 1 ° C. until the total current reached 75% of the theoretical amount, followed by lowering the current to a 75 mA constant current.

After passing the theoretical current, 1-methyl-3-hydroxy-5, 6-dioxo-2, 3, 5, 6-tetrahydroindole produced in the anolyte solution was taken and 1.5 g of semicarbazide hydrochloride was added. Mixed.

The mixture was treated in the same manner as in Example 1 to give red crystals 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole 1.97 g was obtained. Yield: 74.2%

The physicochemical properties of the product were the same as those of the material obtained in Example 1.

Example 8

3,4-Dihydroxy-α-[(methylamino) methyl] benzyl alcohol, 2.74 g, sodium acetate trihydrate 4.08 g, a mixture of 3.44 ml of acetic acid and 137 ml of water were installed so that the positive and negative electrodes were separated by an anion exchange membrane. It was placed in the anode chamber in the electrolytic cell.

A mixture of 4.08 g of sodium acetate and trihydrate and 137 ml of water was added thereto.

Graphite electrodes (5 x 8 cm 2) were placed in parallel in each anode chamber.

Electrolysis was carried out under vigorous stirring at a constant current of 204 mA at 1 ° C. until the total current reached 75% of the theoretical amount, followed by lowering the current to a constant current of 100 mA.

After passing the theoretical amount of current, take 1-methyl-3-hydroxy-5, 6-dioxo-2, 3, 5, 6-tetrahydroindole produced in the anolyte solution, and 2.0 g of semicarbazide hydrochloride. Mixed.

The mixture was treated in the same manner as in Example 1 to give red crystals 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole 2.90 g was obtained. Yield: 82.2%

The physicochemical properties of the product were the same as those of the material obtained in Example 1.

Example 9

The reaction was carried out in the same manner as in Example 8 except that the internal temperature of the anolyte solution was maintained at 5 ° C instead of 1 ° C.

2.59 g of 1-methyl-3-hydroxy-5-semicarbazono-6-oxo-2, 3, 5, 6-tetrahydroindole as red crystals were obtained. Yield: 73.4%

The physicochemical properties of the product were the same as those of the material obtained in Example 1.

Example 10

3, 4-dihydroxy-α-[(methylamino) methyl] benzyl alcohol, 1.37 g, sodium acetate, 1.23 g, a mixture of 1.72 ml of acetic acid and 137 ml of water, the anode in the electrolytic cell installed to separate the anode and cathode by an anion exchange membrane Put it indoors.

Also, a mixture of 1.23 g of sodium acetate and 137 ml of water was added thereto. Graphite electrodes (4 x 5 cm 2) were placed in parallel in each anode chamber.

Electrolysis was carried out under vigorous stirring with a constant current of 100 mA until the total current reached 75% of the theoretical amount, after which the current was lowered to a constant 75 mA.

The internal temperature of the anolyte was kept at 1 ° C. during electrolysis.

After passing the theoretical current, 1-methyl-3-hydroxy-5, 6-dioxo-2, 3, 5, 6-tetrahydroindole produced in the anolyte solution was taken and 1.0 g of semicarbazide hydrochloride was added. Mixed.

The mixed solution was treated in the same manner as in Example 1 to give red crystals 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole 1.39 g was obtained. Yield: 78.5%

The physicochemical properties of the product were the same as those of the material obtained in Example 1.

Example 11

The reaction was carried out in the same manner as in Example 10 except that the internal temperature of the anolyte solution was maintained at 5 ° C instead of 1 ° C.

1.37 g of 1-methyl-3-hydroxy-5-semicarbazono-6-oxo-2, 3, 5, 6-tetrahydroindole, which are red crystals, were obtained. Yield: 77.4%

The physicochemical properties of the product were the same as those of the material obtained in Example 1.

Example 12

3, 4-dihydroxy-α-[(methylamino) methyl] benzyl alcohol, 2.06 g, sodium acetate, 1.85 g, a mixture of 2.58 ml of acetic acid and 137 ml of water, the positive electrode and the negative electrode in an electrolytic cell installed to separate the negative electrode with an anion exchange membrane. Put it indoors.

In addition, a mixture of 1.85 g of sodium acetate and 137 ml of water was added thereto. Graphite electrodes (4 x 5 cm 2) were placed in parallel in each anode chamber. The electrolysis was carried out under vigorous stirring with a constant current of 150 mA until the total current reached 75% of the theoretical amount, after which the current was lowered to a constant current of 112 mA.

The internal temperature of the anolyte was kept at 1 ° C. during electrolysis.

After passing the theoretical current, 1-methyl-3-hydroxy-5, 6-dioxo-2, 3, 5, 6-tetrahydroindole produced in the anolyte solution was taken and 1.5 g of semicarbazide hydrochloride was added. Mixed.

The mixture was treated in the same manner as in Example 1 to give red crystals, 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole 2.11 g was obtained. Yield: 79.4%

The physicochemical properties of the product were the same as those of the material obtained in Example 1.

Example 13

As a device, a filter press type electrolyzer was used, in which a positive electrode plate and a negative electrode plate (14 × 28.5 cm 2 graphite plates, respectively) separated by an anion exchange membrane, and two tanks containing an anolyte and a catholyte were installed.

A mixture of 3,4-dihydroxy-α-[(methylamino) methyl] benzyl alcohol, that is, 13.9 g of adrenaline, 278.6 g of sodium acetate and trihydrate, 11.7 ml of acetic acid, and 2500 ml of water was placed in a positive electrode and a tank. A mixture of 278.6 g of trihydrate and 2830 ml of water was placed in a catholyte tank.

Both anolyte and catholyte are circulated between the tank and the electrolyzer, the current is initially 8.0A, and then gradually lowered to a current such that excessive oxidation of the product (adrenochrome) does not occur. This state was maintained until all the positive current passed.

The internal temperature of the anolyte was maintained at 3-8 ° C. during electrolysis.

After the reaction was completed, the adrenochrome produced in the anolyte, i.e., 1-methyl-3-hydroxy-5, 6-dioxo-2, 3, 5, 6-tetrahydroindole, was taken to give semicarbazide hydrochloride. Mixed with 7.4 g.

The mixture was adjusted to pH 5.2 with saturated sodium carbonate solution under vigorous stirring and stirred at 8 ° C. overnight.

The precipitated crystals were collected by filtration, washed with 100 ml of ice water, and then 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydrolinedol of red crystals. (That is, 44.0 g of adrenochrome monosemicabazone) was obtained. Yield: 91.1%

NMR (d ₆ -DMSO) δ: 3.01 (s, 3H), 3.33-4.2 (m, 2H), 4.8-5.2 (m, 1H), 5.38 (s, 1H), 5.75 (d, 1H, J = 5Hz ), 6.72 (s, 1H), 7.02 (broad, 2H), 14.71 (broad, 1H)

Example 14

Sodium acetate trihydrate, an auxiliary electrolyte added to the catholyte, was reacted in the same manner as in Example 13 except that 13.9 g was used instead of 278.6 g.

43.2 g of red crystals 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole were obtained. Yield: 89.4%

The physicochemical properties of the product were the same as those of the material obtained in Example 13.

Example 15

Sodium acetate trihydrate, an auxiliary electrolyte added to the catholyte solution, was reacted in the same manner as in Example 13 except that 55.7 g was used instead of 278.6 g.

43.9 g of red crystals, 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole were obtained. Yield: 90.9%

The physicochemical properties of the product were the same as those of the material obtained in Example 13.

Example 16

In the same manner as in Example 13, except that 55.7 g of sodium acetate trihydrate, which is an auxiliary electrolyte added to the catholyte, was used instead of 278.6 g of sodium acetate trihydrate without being added to the anolyte solution. Reacted.

43.8 g of red crystals 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole were obtained. Yield: 90.7%

The physicochemical properties of the product were the same as those of the material obtained in Example 13.

Example 17

In Example 13, 13.9 g of sodium acetate trihydrate and 11.7 ml of acetic acid were added to the anolyte solution, and the reaction was carried out in the same manner as in Example 13, except that 111.4 g and 117.0 ml were respectively exceeded.

36.2 g of 1-methyl-3-hydroxy-5-semicarbazono-6-oxo-2, 3, 5, 6-tetrahydroindole, which are red crystals, were obtained. Yield: 74.9%

The physicochemical properties of the product were the same as those of the material obtained in Example 13.

Claims (17)

Electrolytic oxidation of 3,4-dihydroxy-α-[(methylamino) methyl] benzyl alcohol in water containing auxiliary electrolytes yielded 1-methyl-3-hydroxy-5, 6-dioxo-2, 1-methyl-3-hydroxy-5-semicarbazono-6-oxo-2, 3, 5, 6-tetrahydro formed by producing 3, 5, 6-tetrahydroindole and reacting it with semicarbazide Method of preparing indole. The 1-methyl-3-hydride according to claim 1, wherein an aqueous solution of 3,4-dihydroxy-α-[(methylamino) methyl] benzyl alcohol is used as the anolyte and an aqueous solution of the auxiliary electrolyte is used as the catholyte. Process for the preparation of roxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole. The method for producing 1-methyl-3-hydroxy-5-semicarbazono-6-oxo-2, 3, 5, 6-tetrahydroindole according to claim 2, wherein the anolyte solution comprises a co-electrolyte. The preparation of 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole according to claim 2 or 3, wherein the auxiliary electrolyte is an alkali metal salt of an organic acid. Way. The 1-methyl-3-hydroxy-5-semicarbazono-6-oxo-2, 3, 5, 6-tetrahydro according to claim 4, wherein the alkali metal salt of the organic acid is sodium formate, sodium acetate or potassium acetate. Method of preparing indole. The process for producing 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole according to claim 4, wherein the organic acid alkali metal salt is sodium acetate. The method for producing 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole according to claim 2, wherein the anolyte contains an organic acid. The process for producing 1-methyl-3-hydroxy-5-semicarbazono-6-oxo-2, 3, 5, 6-tetrahydroindole according to claim 7, wherein the organic acid is acetic acid. 8. The anolyte according to any one of claims 2, 3, and 7, wherein 0.0-4.0 mol of sodium acetate is added to 1 mol of 3,4-dihydroxy-α-[(methylamino) methyl] benzyl alcohol. The manufacturing method of 1-methyl-3-hydroxy-5-semicarbazono-6-oxo-2, 3, 5, 6-tetrahydroindole containing. 8. The anolyte according to any one of claims 2, 3 and 7, wherein the anolyte contains 1.0-10.0 mol of acetic acid per 1 mol of 3,4-dihydroxy-α-[(methylamino) methyl] benzyl alcohol. 1-methyl-3-hydroxy-5-semicarbazono-6-oxo-2, 3, 5, 6-tetrahydroindole. The anolyte according to any one of claims 2, 3, and 7, 1.0-2.0 mol of acetic acid, sodium based on 1 mol of 3, 4-dihydroxy-α-[(methylamino) methyl] benzyl alcohol A process for preparing 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole containing 0.0-0.5 mole of acetate. 3. The 1-methyl-3-hydroxy- according to claim 2, wherein the catholyte contains 0.5-60.0 moles of sodium acetate per mole of 3, 4-dihydroxy-α-[(methylamino) methyl] benzyl alcohol. Process for preparing 5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole. The process for preparing 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole according to claim 1, wherein the electrolytic oxidation is carried out at 0-10 ° C. . The 1-methyl-3-hydroxy- according to claim 1, wherein the electrolytic oxidation is performed in an electrolytic cell in which a plurality of positive electrode plates and negative electrode plates are arranged in parallel to each other and a diaphragm is disposed between the positive electrode plates and the negative electrode plates. Process for preparing 5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole. The process for producing 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole according to claim 14, wherein the diaphragm is an anion exchange membrane. The process for producing 1-methyl-3-hydroxy-5-semicabazono-6-oxo-2, 3, 5, 6-tetrahydroindole according to claim 14, wherein the electrolytic cell is a filter press type. The 1-methyl-3-hydroxy according to claim 1, wherein the electrolytic oxidation is performed in an electrolytic cell in which the anode chamber and the cathode chamber are disposed opposite each other, and one anode plate and one cathode plate are disposed in parallel in each compartment. -5-Semicarbazono-6-oxo-2, 3, 5, 6-tetrahydroindole.