Method for synthesizing menadiol acetate

Abstract

The invention relates to a novel method for synthesizing menadiol acetate, which includes the steps: reducing 2-methyl-1,4-aryl-quinone to 2-methyl-1,4-aryl-diphenol via anhydrous zinc chloride and zinc acetate in the presence of HAc (ethanoic acid), then carrying out backflow reaction by means of acetylation of (CH3CO)2O ( acetic anhydride) under the catalysis of NaAc (sodium acetate) to obtain crude menadiol acetate, and obtaining the menadiol acetate after purification. The reduction reaction of 2-methyl-1,4-naphthoquinone can be still completely carried out without adding excessive zinc powder, so that severe waste of the zinc powder is avoided, and a large potential safety hazard that the excessive zinc powder is unsafe in placement after being separated and easy to spontaneously combust is avoided. The method is mild in reaction condition, suitable for industrialized production and high in yield.

Description

technical field

[0001] The invention relates to derivatives of naphthoquinones, in particular to a new method for synthesizing menadione acetate. Background technique

[0002] Menahydroquinone acetate, the chemical name is 2-methyl-1,4-naphthalenediol diacetate, also known as vitamin K4, is a white or white crystalline powder, almost insoluble in water, slightly soluble in ethanol, but easily Soluble in boiling ethanol, it is a synthetic vitamin that belongs to the derivatives of naphthoquinones. It is mainly used clinically for various coagulation disorders caused by vitamin K deficiency.

[0003] The method for preparing menadione acetate in the past mainly is to adopt a large amount of excess zinc dust to reduce 2-methyl-1,4-naphthoquinone to obtain 2-methyl-1,4-naphthalenediol, and then make it under the catalysis of sodium acetate 2-Methyl-1,4-naphthalenediol is acetylated to obtain crude menadione acetate, and then purified to obtain the finished product.

[0004] Ho...

Examples

Embodiment 1

[0028] Put 90 parts by weight of glacial acetic acid into the reaction kettle, slowly add 53 parts by weight of dry 2-methyl-1,4-naphthoquinone under stirring, stir to form a paste, add 20.5 parts by weight of zinc powder at a controlled temperature of 35°C, Then add the anhydrous zinc chloride of 8 weight parts again, continue stirring reaction 40min after adding;

[0029] Slowly add 140 parts by weight of acetic anhydride under stirring, then add 28 parts by weight of NaAc in 4 times, heat up to 138 ° C, boil and reflux for 3 hours, leave to cool to room temperature, filter off zinc chloride and NaAc, the resulting liquid is continuously Pour it into a large amount of ice water under stirring, let it stand for 1 hour, filter, wash with water until it is acid-free, and dry to obtain the crude menadione acetate.

[0030] Dissolve the crude product in about 5 times of hot ethanol solution (ethanol: water = 9: 1), add 1%-2% activated carbon and stir for 30 minutes to filter whil...

Embodiment 2

[0032] Put 100 parts by weight of glacial acetic acid into the reactor, slowly add 62 parts by weight of dry 2-methyl-1,4-naphthoquinone under stirring, stir to form a paste, add 25.9 parts by weight of zinc powder at a controlled temperature of 35°C, Then add the anhydrous zinc chloride of 12 weight parts again, continue stirring reaction 40min after adding;

[0033] Slowly add 160 parts by weight of acetic anhydride under stirring, then add 30 parts by weight of NaAc in 8 times, heat up to 138°C, boil and reflux for 3h, leave to cool to room temperature, filter off zinc chloride and NaAc, and the resulting liquid is continuously Pour it into a large amount of ice water under stirring, let it stand for 1 hour, filter, wash with water until it is acid-free, and dry to obtain the crude menadione acetate.

[0034] Dissolve the crude product in about 5 times of hot ethanol solution (ethanol: water = 9: 1), add 1%-2% activated carbon and stir for 30 minutes to filter while hot, fr...

Embodiment 3

[0036] Put 95 parts by weight of glacial acetic acid into the reaction kettle, slowly add 58 parts by weight of dry 2-methyl-1,4-naphthoquinone under stirring, stir to form a paste, add 23.2 parts by weight of zinc powder at a controlled temperature of 35°C, Then add the anhydrous zinc chloride of 10 weight parts again, continue stirring reaction 40min after adding;

[0037] Slowly add 150 parts by weight of acetic anhydride under stirring, then add 29 parts by weight of NaAc in 6 times, heat up to 138°C, boil and reflux for 3h, leave to cool to room temperature, filter off zinc chloride and NaAc, and the resulting liquid is continuously Pour it into a large amount of ice water under stirring, let it stand for 1 hour, filter, wash with water until it is acid-free, and dry to obtain the crude menadione acetate.

[0038] Dissolve the crude product in about 5 times of hot ethanol solution (ethanol: water = 9: 1), add 1%-2% activated carbon and stir for 30 minutes to filter while ...

technical field

[0001] The invention relates to derivatives of naphthoquinones, in particular to a new method for synthesizing menadione acetate. Background technique

[0002] Menahydroquinone acetate, the chemical name is 2-methyl-1,4-naphthalenediol diacetate, also known as vitamin K4, is a white or white crystalline powder, almost insoluble in water, slightly soluble in ethanol, but easily Soluble in boiling ethanol, it is a synthetic vitamin that belongs to the derivatives of naphthoquinones. It is mainly used clinically for various coagulation disorders caused by vitamin K deficiency.

[0003] The method for preparing menadione acetate in the past mainly is to adopt a large amount of excess zinc dust to reduce 2-methyl-1,4-naphthoquinone to obtain 2-methyl-1,4-naphthalenediol, and then make it under the catalysis of sodium acetate 2-Methyl-1,4-naphthalenediol is acetylated to obtain crude menadione acetate, and then purified to obtain the finished product.

[0004] Ho...

Examples

Embodiment 1

[0028] Put 90 parts by weight of glacial acetic acid into the reaction kettle, slowly add 53 parts by weight of dry 2-methyl-1,4-naphthoquinone under stirring, stir to form a paste, add 20.5 parts by weight of zinc powder at a controlled temperature of 35°C, Then add the anhydrous zinc chloride of 8 weight parts again, continue stirring reaction 40min after adding;

[0029] Slowly add 140 parts by weight of acetic anhydride under stirring, then add 28 parts by weight of NaAc in 4 times, heat up to 138 ° C, boil and reflux for 3 hours, leave to cool to room temperature, filter off zinc chloride and NaAc, the resulting liquid is continuously Pour it into a large amount of ice water under stirring, let it stand for 1 hour, filter, wash with water until it is acid-free, and dry to obtain the crude menadione acetate.

[0030] Dissolve the crude product in about 5 times of hot ethanol solution (ethanol: water = 9: 1), add 1%-2% activated carbon and stir for 30 minutes to filter whil...

Embodiment 2

[0032] Put 100 parts by weight of glacial acetic acid into the reactor, slowly add 62 parts by weight of dry 2-methyl-1,4-naphthoquinone under stirring, stir to form a paste, add 25.9 parts by weight of zinc powder at a controlled temperature of 35°C, Then add the anhydrous zinc chloride of 12 weight parts again, continue stirring reaction 40min after adding;

[0033] Slowly add 160 parts by weight of acetic anhydride under stirring, then add 30 parts by weight of NaAc in 8 times, heat up to 138°C, boil and reflux for 3h, leave to cool to room temperature, filter off zinc chloride and NaAc, and the resulting liquid is continuously Pour it into a large amount of ice water under stirring, let it stand for 1 hour, filter, wash with water until it is acid-free, and dry to obtain the crude menadione acetate.

[0034] Dissolve the crude product in about 5 times of hot ethanol solution (ethanol: water = 9: 1), add 1%-2% activated carbon and stir for 30 minutes to filter while hot, fr...

Embodiment 3

[0036] Put 95 parts by weight of glacial acetic acid into the reaction kettle, slowly add 58 parts by weight of dry 2-methyl-1,4-naphthoquinone under stirring, stir to form a paste, add 23.2 parts by weight of zinc powder at a controlled temperature of 35°C, Then add the anhydrous zinc chloride of 10 weight parts again, continue stirring reaction 40min after adding;

[0037] Slowly add 150 parts by weight of acetic anhydride under stirring, then add 29 parts by weight of NaAc in 6 times, heat up to 138°C, boil and reflux for 3h, leave to cool to room temperature, filter off zinc chloride and NaAc, and the resulting liquid is continuously Pour it into a large amount of ice water under stirring, let it stand for 1 hour, filter, wash with water until it is acid-free, and dry to obtain the crude menadione acetate.

[0038] Dissolve the crude product in about 5 times of hot ethanol solution (ethanol: water = 9: 1), add 1%-2% activated carbon and stir for 30 minutes to filter while ...

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