KR100517343B1 - Preparation method of Methoxyphenylhydrazine - Google Patents

Abstract

The present invention relates to a method for producing methoxyphenylhydrazine, and more particularly, to a sulfite and hydrogen sulfite as a reducing reagent of methoxyphenyldiazonium salt which is neutralized with acid and oxidized by nitrite from methoxyphenylamine or its derivatives. By using sequential reduction reaction under certain conditions to produce methoxyphenylhydrazine, it is an eco-friendly and inexpensive production process with low cost reducing reagent, mild reaction condition and no heavy metal waste. And a method for producing methoxyphenylhydrazine which can be usefully used in the fine chemical industry such as plastic additives.

Description

Preparation method of methoxyphenylhydrazine {Preparation method of Methoxyphenylhydrazine}

The present invention relates to a method for producing methoxyphenylhydrazine, and more particularly, to a sulfite and hydrogen sulfite as a reducing reagent of methoxyphenyldiazonium salt which is neutralized with acid and oxidized by nitrite from methoxyphenylamine or its derivatives. By using sequential reduction reaction under certain conditions to produce methoxyphenylhydrazine, it is an eco-friendly and inexpensive production process with low cost reducing reagent, mild reaction condition and no heavy metal waste. And a method for producing methoxyphenylhydrazine which can be usefully used in the fine chemical industry such as plastic additives.

According to Milos Hudlisky's Reduction in Organic Chemistry, John Willey & Sons, 1984, a method for reducing conventional organic compounds is described for the synthesis of hydrazine from diazonium salts. have.

See also Fischer E., Ann Chem. 190, 67-188, 1878; Reychler A., Chem. Ber. 20, 2463 to 2089, 1887 describe in detail a method for reducing phenyl and phenyl derivatives of diazonium, ie, diazotization from aniline or nitrophenylamine to reduce and synthesize hydrazine. In this document, a method of reducing phenyl and phenyl derivatives of diazonium, which is reduced by using potassium sulfite (K ₂ SO ₃ ) or sodium sulfite (Na ₂ SO ₃ ) alone as a reducing agent, and zinc (Zn) ) And a method for synthesizing hydrazine derivatives by hydrogen reduction using acetic acid (CH ₃ COOH). Such a reduction method is not currently reduced in the known reduction methods or derivatives having a methoxy group attached to phenyl.

Therefore, paramethoxyphenylhydrazine synthesis method [JCS 125 (1), 313, 1924] is prepared by dropping paramethoxyphenylamine (p-anisidine) in a strong hydrochloric acid solution to form a salt, and methoxyphenyldiazonium salt in aqueous sodium nitrite solution. Then, using a high reagent tin chloride (II) (SnCl ₂ ) as a reducing agent was reduced at low temperatures to make paramethoxyphenylhydrazine. This method is also difficult to produce alkoxyphenylamines made from methoxyphenylamines (o-Anisidine, m-Anisidine and p-Anisidine) in the olso, meta, or para-positions without the reduction described above. Therefore, the conventional general method is not reduced by using only sodium sulfite (Na ₂ SO ₃ ) or sodium hyposulfite (Na ₂ S ₂ O ₄ ) commonly used due to thermal instability of methoxyphenyldiazonium, Under strong acidity, it uses the reducing action of divalent tin, a heavy metal. This low temperature reduction reaction causes slurry in the reactor to precipitate or solidify due to precipitation of tin chloride (IV) generated during the reduction process. do. In addition, the waste treatment caused by the heavy metals of tin oxide, which is produced as a by-product after neutralization, has a problem of industrialization and is expensive compared to other reducing reagents.

Another method is not an industrial method, but an electroreduction method [J. Electrochemical Science and technology, Olivier Orange, etc, Vol. 128, No. 9, 1889-1894, 1981], hexafluoroborate of anion chlorine as sodium hexafluoroborate (NaBF ₆ ) in paramethoxydiazonium salts. It is a method of stabilizing salts by substituting with ions and producing paramethoxyhydrazine using an electrochemical reduction method using a mercury electrode. Sodium hexafluoroborate, which is used to stabilize diazonium hydrochloride, is an expensive reagent and consists of a process that is difficult to recover and reuse. In addition, in order to use the electrochemical method, it should be used at a very low concentration ( ^10-4 mol), and the yield is about 65%. This condition is very oxidative, and there is a problem in industrialization.

On the other hand, using a sulfite salt of the existing reduction method [Org syn coll vol 1, pp 442-445 or Mann & Saunders, Practical Organic Chemistry, 3rd Ed] to produce phenylhydrazine from aniline without a methoxy group (Aniline) When the alkoxy phenyl hydrazine is not synthesized due to the following problems effectively. The preparation of the alkoxyphenylhydrazine differs from the synthesis of phenylhydrazine, so that the alkoxyphenyldiazonium salt is made of alkoxyphenyldiazosulphate as sodium sulfite in the alkoxyphenyldiazonium salt. This is not made. The reason for this is that alkoxy groups are electron-gripping roles and low energy bonds. Since alkoxyphenyldiazo salts are very weak to acids and heat, they are completely dissolved by heating the alkoxyphenyldiazosulphite salt. The phenyldiazosulphite salt is neutralized with hydrochloric acid to precipitate into a more stable insoluble alkoxydiazosulphite salt, or under weak acidity, decomposes with the generation of nitrogen to form tar and no reduction [Ber. R. Huisgen and R. Lux, Jahrg. 93, 1960, pp 540-544. Alternatively, dropping the aqueous solution of sodium alkoxyphenyldiazosulphite into a hot aqueous solution at 60 to 90 ° C. causes partial reduction and decomposition, resulting in the formation of tar, which does not increase the yield of hydrazine by more than 35%.

Another method for producing phenylhydrazine from aniline without methoxy group is the reduction of organic compounds commonly used, such as direct hydrogen reduction by a catalyst or reduction methods with strong acids and metals. Due to the decomposition of the diazo and thermal instability due to the formation of tar is not used a lot.

As such, methoxyphenylhydrazine or its derivatives, which are used as intermediates in medicine, pesticides, dyes, and plastic additives, are intermediates of novel substances with new properties. It is being distributed in the market, which is an obstacle to the development of the fine chemical industry such as commercialization of new products.

Accordingly, the present inventors control the reduction of methoxyphenyldiazonium salt formed by neutralization with acid and oxidized by nitrite from methoxyphenylamine (Anisidine) or its derivatives to pH 6-10 with sulfite to solve the above problems. To prepare methoxyphenyldiazosulphite, which was then adjusted to pH 5-7 with hydrogen sulfite to prepare methoxyphenylhydrazine sulfite by hydrolysis reduction with the reaction of hydrogen sulfite, followed by hydrolysis with hydrochloric acid. The present invention was completed by preparing methoxyphenylhydrazine hydrochloride by a method of reducing and then neutralizing the methoxyphenylhydrazine hydrochloride with caustic soda to produce methoxyphenylhydrazine.

Accordingly, the present invention provides a method for producing methoxyphenylhydrazine with high yield because of the environmentally friendly and economical as well as mild reaction conditions by using an environment-friendly and inexpensive reducing agent in the synthesis of methoxyphenylhydrazine. There is this.

The present invention is a method of producing methoxyphenyl hydrazine from the methoxyphenylamine hydrochloride or methoxyphenylamine hydrochloride, methoxyphenyldiazonium salt, methoxyphenylhydrazine sulfite and methoxyphenylhydrazine hydrochloride from As a reducing reagent of the methoxyphenyldiazonium salt, sulfite (M ₂ SO ₃ ; M is Na or K) and hydrogen sulfite (MHSO ₃ ; M is Na or K) are sequentially reduced to react methoxyphenylhydrazine. It is characterized by the manufacturing method.

Referring to the present invention in more detail as follows.

In general, diazonium salts of phenyl derivatives are very weak to temperature, so that decomposition occurs easily. In particular, when the phenyl group contains the oxy, methoxy, halogen groups of the electrophilic radicals, the diazonium salts tend to be more decomposed while releasing nitrogen, so it is difficult to reduce them to conventional methods to form hydrazine compounds.

Accordingly, the present invention is a sulfite commonly used for neutralization by acid and reduction of methoxyphenyldiazonium salt formed by oxidation of nitrite from methoxyphenylamine or a derivative thereof, and methoxyphenyldiazosulphite at a specific pH and at a specific temperature. The precipitate was made and stabilized, and then the aqueous hydrosulfite solution was added again, and then pH and reaction temperature were adjusted to form methoxyphenylhydrazine sulfite, which was hydrolyzed and neutralized to produce methoxyphenylhydrazine. Since there is no decomposition of tar, there is no tar formation, the yield is very high, and it is environmentally friendly, and the reaction conditions are gentle, so that methoxyphenylhydrazine can be produced at low cost.

Such a method for producing methoxyphenylhydrazine according to the present invention will be described in more detail as follows.

First, methoxyphenylamine or a derivative thereof and hydrochloric acid react in one step to form methoxyphenylamine hydrochloride (1) according to the following scheme 1.

In the above scheme, R ₁ represents a methoxy (OCH ₃ ) radical (hereinafter R ₁ is the same).

The reaction is slowly added dropwise methoxyphenylamine or its derivatives to a strong hydrochloric acid solution at a low temperature of 0 to 20 ℃, preferably 5 to 10 ℃ (near the melting point of methoxyphenylamine) to produce methoxyphenylamine hydrochloride. do.

In two steps, the methoxyphenylamine hydrochloride is reacted with nitrite to form a methoxyphenyldiazonium salt (2) according to the following scheme 2.

The reaction is oxidized by dropwise addition of an aqueous nitrite solution to methoxyphenylamine hydrochloride while maintaining the reaction temperature at 0 to 20 ℃, preferably 0 to 10 ℃ to methoxyphenyl diazonium salt. At this time, stoichiometric hydrochloric acid participates in the reaction more than 1.0 mol times, so the amount of hydrochloric acid is added before the reaction sufficiently starts. After the reaction, the solution becomes deep blue.

In three steps, the methoxyphenyldiazonium salt is reacted with sulfite to form methoxyphenyldiazosulphite (3) according to the following scheme 3.

The reaction maintains the temperature of the reactor at room temperature or lower, preferably 0 to 10 ° C. Then, sodium sulfite (Na ₂ SO ₃ ) is measured at a molar ratio of 1 to 1.5 with respect to the methoxyphenyldiazonium salt, and distilled water is poured to be a saturated solution at room temperature and dissolved completely. This aqueous solution is moved to another reactor, and the temperature of a reactor is reduced to 0-20 degreeC, Preferably it is 0-10 degreeC. If the reaction temperature is less than 0 ℃, the reaction rate is slow due to the crystallization of the raw material, the complete reaction is difficult, and there is a problem of causing excessive consumption of power by subcooling. If it exceeds 20 ℃, tar is formed by decomposition of the diazonium salt, yield There is a problem of this lowering. At this time, the saturated aqueous sodium sulfite solution in the reactor becomes supersaturated to produce a white precipitate, regardless of this, the temperature of the reactor is kept at a low temperature. Then, while the methoxyphenyldiazonium salt of Scheme 2 is added to an aqueous solution of supersaturated sodium sulfite, the pH of the reaction mixture is often neutral or weakly alkaline (pH 6-10), preferably as pH paper or pH meta. The pH is adjusted to 7-9 to obtain yellow precipitate, which is methoxyphenyldiazosulphite. If the pH is less than 6, thermally stable and insoluble methoxyphenyldiazosulphite is formed, which leads to an undesirable reaction and lowers the yield.When the pH exceeds 10, the diazonium salt is very weak to alkali and decomposes. There is a problem that tar is generated. After mixing, the temperature of the reactor was raised to room temperature and maintained for 1 to 3 hours to complete the reaction, thereby obtaining methoxyphenyldiazosulphite.

In a four step, the methoxyphenyldiazosulphite is reacted with hydrogen sulfite to form methoxyphenylhydrazine sulfite (4) according to the following scheme 4.

The reaction was determined by dissolving sodium hydrogen sulfite (NaHSO ₃ ) in a 1 to 1.5 molar ratio with respect to the methoxyphenyldiazonium salt, adding distilled water to be saturated at room temperature, and then adding this aqueous solution to the methoxyphenyldiazosulphite prepared above. When the pH of the solution is measured from time to time, the pH of the solution is weakly acidic, preferably pH is adjusted to 5-7, and slowly heated to 50-95 ℃, preferably the reaction proceeds to raise the temperature to completely dissolve the methoxyphenyl Diazosulfite dissolves completely and reacts with sodium bisulfite. If the pH is less than 5, there is a problem that precipitation of methoxyphenyldiazonium bisulfite, which is stable to heat and insoluble in water, is generated. If the pH is above 7, the concentration of sodium bisulfite is lowered, thereby rapidly decreasing the reaction yield. There is. If the reaction temperature is less than 50 ℃ methoxyphenyldiazonium sulfite does not dissolve, there is a problem that the reaction rate is very slow, and if it exceeds 95 ℃, the weak diazonium salt or hydrazine salt formed by heat decomposes by heat, tar is formed, yield There is a difficult problem in purification and lowering. This reaction occurs very quickly, and the intermediate product produced here is converted to a clear pale red yellow solution by the production of sodium methoxyphenylhydrazine sulfite (4) by reduction by hydrolysis with one molecule of water. The reduction reaction by hydrolysis is a very slow reaction, and the reaction proceeds at least about 90% at a temperature between 70 and 80 ° C. usually between 2 and 4 hours. Observe the progress of the reaction by HPLC to cool the solution to room temperature if the reaction rate is more than 90% and no further reaction. Sodium methoxyphenylhydrazine sulfite, the reaction solution after cooling, has a transparent reddish yellow color without precipitation.

In step 5, methoxyphenylhydrazine sulfite forms methoxyphenylhydrazine hydrochloride (5) according to the following scheme.

The reaction was performed by quantitatively stirring the concentrated hydrochloric acid in an aqueous solution of sodium methoxyphenylhydrazine sulfite in Scheme 4 at about 5 to 10 molar ratios, preferably 7 to 9 molar ratios, with respect to the methoxyphenyldiazonium salt at 10 to 65 ° C. When stirred, methoxyphenylhydrazine sulfite rapidly becomes a methoxyphenylhydrazine hydrochloride by reduction reaction by hydrolysis with one molecule of water. At this time, when the concentration of hydrochloric acid is increased, the rate of hydrolysis reduction is increased, and the stability of heat of the hydrazine salt is increased, but the amount of alkali for neutralization is increased, thereby increasing the manufacturing cost. When the concentration of hydrochloric acid is low, the rate of hydrolysis reduction is low, and it is easy to decompose, resulting in greater tar formation and lower yield. In addition, if the temperature of the hydrolysis reduction is less than 10 ℃, the reduction reaction rate by the hydrolysis is slow, the completion time is slow, and if the temperature exceeds 65 ℃, the progress of the hydrolysis reduction reaction is faster, but the decomposition is accelerated to accelerate the formation of tar, yield It is difficult to purify by lowering the concentration and increasing the concentration of impurities. After the hydrolytic reduction reaction with strong hydrochloric acid is completed, the temperature of the reactor is lowered to 0 to 10 ° C.

In six steps, methoxyphenylhydrazine hydrochloride forms methoxyphenylhydrazine (6) according to Scheme 6 below.

The reaction is neutralized by adding strong alkali (caustic soda) to the aqueous solution of methoxyphenylhydrazine hydrochloride of Scheme 5 at 0 to 20 ° C., preferably at 0 to 10 ° C., so that the pH of the aqueous solution is weakly alkaline, preferably pH. It adjusts to 10-12 and obtains methoxyphenylhydrazine. Since the prepared methoxyphenyl hydrazine is dispersed in the form of red oil in the upper layer of the aqueous solution, it is extracted 2 to 4 times with an organic solvent insoluble in water such as toluene, benzene, hexane, ethyl acetate, etc. Recover by vacuum distillation at low temperature. The methoxyphenylhydrazine extracted in the solvent at this time shows a purity of 95% or more by HPLC analysis. Alternatively, the yield of the crystalline methoxyphenylhydrazine recovered by the reaction with methylchloroformate in the extraction solution is 85% or more, which is very economical compared to other synthetic methods.

Hereinafter, the present invention will be described in more detail with reference to Examples, but the present invention is not limited by Examples.

Example 1 Na ₂ SO ₃  And NaHSO ₃ Reduction by

The stirrer and thermometer were attached to a 1000 ml double jacket reactor, and 85 ml of concentrated hydrochloric acid (37%) was added to circulate the cooling water through the outer jacket of the reactor, and the temperature of the reactor was lowered below 5 ° C. 49.96 g (0.4057 mol) of orthomethoxyphenylamine (o-Anisidine, 99 +% aldrich) was slowly added thereto to prepare a slurry solution of white crystal o-AnisidineHCl salt (1). 30.30 g (0.4057 mol) of sodium nitrite (NaNO ₂ ; 97%, Aldrich) was dissolved in 56 ml of water, and the prepared solution was slowly injected into the reactor and reacted with o-AnisidineHCl salt to give a deep blue 2-methoxy- A phenyl diazonium salt (2) was made. The 2-methoxy-phenyl diazonium salt aqueous solution was transferred to another container and stored at 5 degrees C or less. After dissolving 61.99 g (0.4665 mol) of sodium sulfite (Na ₂ SO ₃ ; 98% Aldrich) in 250 ml of water, divide the solution into two and put about 67% of the solution into the reactor. After close proximity, it was placed in another container. When the temperature of the reactor is lowered to 0 ° C, white precipitate of sodium sulfite is generated, but irrespective of this, the prepared 2-methoxy-phenyldiazonium salt aqueous solution is added to adjust the pH to about 7, and the remaining sodium sulfite aqueous solution is added to adjust the pH. I set it to about 8. The aqueous 2-methoxy-phenyl diazonium salt was reacted with sodium sulfite to produce a golden precipitate, i.e., 2-methoxy-phenyl diazonium sulfite (3). After the reaction, the temperature of the reactor was raised to room temperature and maintained for about 1 hour. 83.08 g (0.4671 mol) of sodium hydrogen sulfite (NaHSO ₃ ; 58.5% Samchun chemical) was dissolved in 150 ml of water, and this aqueous solution was added to the reactor. The pH was adjusted to about 6 with concentrated hydrochloric acid, and then slowly heated. As the precipitate in the reactor began to melt, the reaction occurred and the pH of the reaction was adjusted to maintain 5-7. After 2 hours at the temperature of melting the reactant, that is, about 70 ℃, the reaction was confirmed that the reaction proceeds by about 93% or more by HPLC analysis, after which the reaction rate is sharply reduced, the solution was a transparent red-yellow. When the concentration of the product, 2-methoxy-phenyl hydrazine sulfite (4), is no longer raised, lower the temperature of the reactor to room temperature and divide it into two parts for about 8 hours at room temperature using concentrated hydrochloric acid (5 molar ratio for diazonium salt). After hydrolysis reduction to obtain 2-methoxy-phenyl hydrazine hydrochloride (5), the temperature was cooled to near 0 ℃ to neutralize with 50% caustic soda. When the pH of the solution was about 12, stopping the injection of alkali and stopping the stirrer, the oil layer of the red 2-methoxy-phenyl hydrazine (6) was seen floating on the upper layer. The produced 2-methoxy-phenyl hydrazine was extracted four times with 500 ml of toluene, and the extracted 2-methoxy-phenyl hydrazine was reacted with methylchloroformate (CH ₃ OCOCl) at 10-20 DEG C in the presence of alkali. The yields of the 2-methoxy-phenyl hydrazine methylcarbamate crystals obtained were 85.2% and 82.94%, respectively, and the HPLC purity was 99.% or more.

Examples 2 to 3.

2-methoxy-phenyl hydrazine was prepared in the same manner as in Example 1, but only the concentration of hydrochloric acid used in the hydrolytic reduction reaction was changed as shown in Table 1 below.

Increasing the amount of hydrochloric acid increases the hydrolysis reduction, and also has excellent thermal stability, thereby increasing the yield. However, when neutralizing the 2-methoxy-phenyl hydrazine hydrochloride produced, a large amount of alkali is required, which leads to an increase in cost, and therefore, an appropriate amount of hydrochloric acid is required from an economic point of view.

Starting material Reductant I Reductant II Hydrochloric acid (mol / mol-raw material) Yield (%) ^* HPLC (%) Example 2 o-Anisidine Na ₂ SO ₃ NaHSO ₃ 7 84.01 93.97 Example 3 " " " 10 86.55 93.29 * Yield of 2-methoxy-phenyl hydrazine methylcarbamate crystals obtained by making hydrazine and then synthesizing with methylchloroformate.

Examples 4 to 5.

Prepare 2-methoxy-phenyl hydrazine in the same manner as in Example 1, but the concentration of hydrochloric acid used in the hydrolysis reduction reaction is 7, and the raw material was changed as shown in Table 2 and reacted with methylchloroformate to determine Obtained and analyzed. The resulting materials were para-methoxy-phenyl hydrazine methyl carbamate and meta-methoxy-phenyl hydrazine methyl carbamate, respectively. The yield and purity were lower than that of ortho-methoxy-phenyl hydrazine as in Example 1.

Starting material Reductant I Reductant II Hydrochloric acid (mol / mol-raw material) yield(%) HPLC (%) Example 4 p-Anisidine Na ₂ SO ₃ NaHSO ₃ 7 50.98 62.58 Example 5 m-Anisidine " " 7 46.78 55.13

Comparative Example 1.SnCl ₂ Reduction by

The stirrer and thermometer were attached to a 1000 ml double jacket reactor, and 122 ml of concentrated hydrochloric acid (37%) and 255 ml of water were added to circulate the cooling water through the outer jacket of the reactor to lower the temperature of the reactor to 5 ° C or lower. Here, 52.09 g (0.4230 mol) of orthomethoxyphenylamine (o-Anisidine, 99 +%, Aldrich) was slowly added to the reactor to form a white crystal o-AnisidineHCl salt. The reaction is neutralized so that the temperature in the reactor rises, so care should be taken not to exceed 10 ℃. After completion of the injection, the reaction was maintained for about 30 minutes. Then, 30.64 g (0.4441 mol) of sodium nitrite (NaNO ₂ ; 97%, Aldrich) was dissolved in 55 ml of water, and the prepared solution was slowly injected into the reactor to react with o-AnisidineHCl salt to react with 2-methoxy-. A phenyl diazonium salt was made. At this time, the diazonium reaction is an exothermic reaction and the product is very sensitive to temperature, which is easy to decompose, thereby maintaining the reaction temperature at about 0 ° C. The 2-methoxy-phenyl diazonium salt produced by the completion of the reaction was a completely dissolved deep blue aqueous solution. To reduce this 2-methoxy-phenyl diazonium salt, a solution of 205.2 g (0.8459 mol) of tin (II) chloride (SnCl ₂ · 2H ₂ O; 93%, Aldrich) completely dissolved in 100 ml of concentrated hydrochloric acid was slowly added to the reactor. And the reaction temperature was kept below 5 ℃. The reaction changed color from orange to light yellow to white and changed to solid phase in the slurry, resulting in poor stirring. After the completion of the injection, the mixture was stirred for about 2 hours at room temperature, and the temperature of the reactor was lowered to near 0 ° C. to neutralize the product as a concentrated caustic soda solution (50% NaOH). Upon neutralization with alkali, the solid phase reacts gradually with melting of alkali. If the alkali is continuously injected, the reactant is solidified with tin hydroxide (IV) again in the pH range of about 3 to 7, and it is difficult to stir and takes a load on the stirring power. However, when alkali is continuously injected, the tin hydroxide IV slowly dissolves again in the alkali region. When the pH of the solution was about 12, stopping the infusion of alkali and stopping the stirrer showed that the oil layer of red o-methoxyphenylhydrazine floated on the upper layer. The resulting o-methoxyphenylhydrazine was extracted four times with 125 ml of toluene, water was removed with 10 g of NaOH, filtered, and the solvent (500 ml) was removed by vacuum distillation to give 53.13 g of o-methoxyphenylhydrazine (yield). 90.9%). In addition, 3- (2-methoxyphenyl) hydrazine methylcarbamate crystals obtained by reacting o-methoxyphenylhydrazine extracted with toluene with methylchloroformate (CH ₃ OCOCl) at 10 to 20 ° C. in alkali presence were 71.68 g ( HPLC purity 99.2%), yield 86.4%. The yield and purity of the orthomethoxyphenylhydrazine and 2-methoxy-phenyl hydrazine methylcarbamate crystals prepared in Comparative Example 1 were not different from those of Examples 1 to 3, and IR, H ¹ -NMR, C ¹³ -NMR, And elemental analysis results. Therefore, it was confirmed that the reduction by Na ₂ SO ₃ and NaHSO ₃ carried out in Examples 1 to 3 is more environmentally friendly and easier to process than Comparative Example 1.

Comparative Example 2. Sodium sulfite (Na ₂ SO ₃ Reduction by

The stirrer and thermometer were attached to a 1000 ml double jacket reactor, and 85 ml of concentrated hydrochloric acid (37%) was added to circulate the cooling water through the outer jacket of the reactor, and the temperature of the reactor was lowered below 5 ° C. To this was slowly added 49.96 g (0.4057 mol) of orthomethoxyphenylamine (o-Anisidine, 99 +% aldrich) to give o-Anisidine.HCl salt (1) as white crystals. 30.30 g (0.4057 mol) of sodium nitrite (NaNO ₂ ; 97%, Aldrich) was dissolved in 56 ml of water, and the prepared solution was slowly injected into the reactor to react with o-AnisidineHCl salt to react with 2-methoxy-phenyl diazo. Made a salt of nium. It was transferred to another container and stored below 5 ° C. Dissolve 122.7 g (0.9736 mol) of sodium sulfite (Na ₂ SO ₃ ; 98% Aldrich) in 450 ml of water, add half of this solution to the reactor, adjust the pH to around 9 with concentrated hydrochloric acid, and then set the temperature of the reactor to 0. When the temperature was lowered to a white precipitate, the pH was adjusted to about 7 by adding the aqueous 2-methoxy-phenyl diazonium salt prepared previously. The aqueous diazo solution reacted with sodium sulfite to produce a golden precipitate. After raising the temperature of the reactor to room temperature and maintaining for about 1 hour, the remaining half of the sodium sulfite aqueous solution was added, adjusted to pH 6 with concentrated hydrochloric acid, and slowly heated. As the precipitate in the reactor began to melt, the reaction occurred. When the pH was changed, the pH was adjusted to around 6 with concentrated hydrochloric acid or 50% caustic soda solution. The precipitate was completely dissolved at the reaction temperature of about 65 ° C. and after about 3 hours, the reaction proceeded to about 94% by HPLC analysis.

The temperature of the reactor was lowered to room temperature, and divided into two to test the amount of hydrazine produced depending on the concentration of hydrochloric acid during hydrolysis. The hydrolysis reduction method is a method of thermal shock to rapidly drop the aqueous solution added hydrochloric acid to the reactor heated to about 65 ℃ and immediately lower the temperature to obtain the hydrazine hydrochloride. When 1 equivalent mol of mol of diazonium was used as concentrated hydrochloric acid, most of the product was changed to tar and disposed of. However, when hydrolysis reduction was carried out using a trivalent mol using concentrated hydrochloric acid, Tar was formed, resulting in a large amount of impurities, but after methylchloroformate reaction, the product was 30.51 g (HPLC purity 94.03%), yielding 76.68%. Got. The synthesis obtained in Example 1 is regarded as the reaction proceeding as a kind of anion present in the aqueous solution depending on the pH of the aqueous sodium sulfite solution. That is, when the pH is 7 or more, SO ₃ ^-2 , and when 7 or less, it is possible to exist as HSO ₃ ^-1 ion.

Comparative Example 3.

The method of making a diazonium salt aqueous solution and using sodium sulfite in the same manner as in Comparative Example 2 is the same, but the pH of the suspension of 2-methoxyphenyldiazosulphite salt and sodium sulfite (Na ₂ SO ₃ ) aqueous solution of only golden precipitate When the reaction is carried out at 7 to 8 to 9 and heated to 70 ° C. to react, the reactant is not dissolved well and is suspended in an ocher suspension. The solution is cooled to room temperature and the reduction reaction by hydrolysis with concentrated hydrochloric acid solution does not proceed. This result shows that the reactivity of the sodium sulfite aqueous solution is highly dependent on pH.

Comparative Example 4.

The method of making a diazonium salt aqueous solution and using sodium sulfite in the same manner as in Comparative Example 2 is the same, but the pH of the suspension of 2-methoxyphenyldiazosulphite salt and sodium sulfite (Na ₂ SO ₃ ) aqueous solution of only golden precipitate When the reaction is conducted at less than 7 to 2 or 3 and heated to 70 ℃, the reactant melts well and the reaction progresses rapidly. Some hydrazines are formed, resulting in tar, and a side reaction of 2-methoxyphenyldiazohydrosulfite. A stable yellow precipitate is formed and suspended in the suspension. If the solution is cooled to room temperature and hydrolyzed and reduced with concentrated hydrochloric acid, the reaction will not proceed. This result shows that the reactivity of the sodium sulfite solution is highly dependent on pH.

As described above, in the method for preparing methoxyphenylhydrazine according to the present invention, the reduction reaction of methoxyphenyldiazonium salt is performed using reduction sulfide and hydrogen sulfite salt sequentially to stabilize the diazonium salt, followed by reduction reaction. No decomposition of diazo compounds, no tar formation, very high yield, environmentally friendly, mild reaction conditions, methoxyphenylhydrazine can be produced at low cost, pharmacy, pesticide, It can be usefully used in the fine chemical industry such as dyes, antioxidants and plastic additives.

Claims (8)

delete Reacting methoxyphenylamine or a derivative thereof with hydrochloric acid to form methoxyphenylamine hydrochloride; Reacting methoxyphenylamine hydrochloride with nitrite to form a methoxyphenyldiazonium salt; Reacting the methoxyphenyldiazonium salt with sulfite (M ₂ SO ₃ ; wherein M is Na or K) at pH 7-9 and 0-10 ° C. to form methoxyphenyldiazosulphite; Reacting the methoxyphenyldiazosulphite with hydrogen sulfite (MHSO ₃ ; where M is Na or K) at a pH of 5 to 7 and 50 to 95 ° C. to form methoxyphenylhydrazine sulfite; Hydrolyzing and reducing methoxyphenylhydrazine sulfite with hydrochloric acid at a temperature of 10 to 65 ° C. to form methoxyphenylhydrazine hydrochloride; And Neutralizing the methoxyphenylhydrazine hydrochloride with caustic soda to form methoxyphenylhydrazine; Method for producing methoxyphenylhydrazine, characterized in that consisting of. delete The method for producing methoxyphenylhydrazine according to claim 2, wherein the sulfite is added in a 1 to 1.5 molar ratio with respect to the methoxyphenyldiazonium salt in the reaction of the three steps. delete 3. The method for producing methoxyphenylhydrazine according to claim 2, wherein the hydrogen sulfite salt is added in a 1 to 1.5 molar ratio with respect to the methoxyphenyldiazonium salt in the reaction of step 4. The method for producing methoxyphenylhydrazine according to claim 2, wherein the hydrochloric acid is added in a 5 to 10 molar ratio with respect to the methoxyphenyldiazonium salt in the reaction of step 5. delete