4-methyl cinnamic acid methyl ester
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Name
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4-methyl cinnamic acid methyl ester
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Molecular Structure
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Alias
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METHYL 4-METHYLCINNAMATE
Methyl trans-4-methylcinnamate
Methyl 3-(p-tolyl)acrylate
methyl (E)-3-(4-methylphenyl)prop-2-enoate
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CAS.No
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20754-20-5
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Molecular formula
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C11H12O2
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Molecular weight
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176.21
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Density
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1.057g/cm3
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Melting Point
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60-61 degree C
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Boiling point
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272.9 degree C at 760 mmHg
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Appearance
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White to light yellow crystalline powder
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Acid value(mgKOH/g)
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Is no more than 3.0
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4-methyl cinnamic acid methyl ester is a pharmaceutical intermediate. It is mainly used for the synthesis of methyl bromomethylcinnamate, the upstream raw material of the antithrombotic drug Ozagrel sodium. Methyl p-methylcinnamate is brominated by N-bromosuccinimide to obtain methyl p-bromomethylcinnamate, methyl p-bromomethylcinnamate in ionic liquid N-n-butylpyridine tetrafluoroboron The acid salt was lyophilized with imidazole at room temperature and then hydrolyzed to obtain an antithrombotic drug, ozagrel sodium, with a total yield of 67%. Methyl p-methylcinnamate is first reacted with p-methylbenzaldehyde and malonic acid to form p-methylcinnamic acid, which is then esterified with p-methylcinnamic acid and methanol to form methyl p-methylcinnamate.
The process for preparing cinnamate by condensation of benzoquinone with acetate is known as the Claisen-Schmidt condensation reaction. The main methods for preparing cinnamate by Claisen-Schmidt reaction are as follows:
1. Prepared with anhydrous ethanol as solvent and 10% NaOH as catalyst, but the method has long reaction time and side reaction.
Should be more, product yield is low, production efficiency is poor.
- The acetic acid ester is used as a solvent and the sodium alkoxide is used as a catalyst to condense. This method improves the product yield, but the post-treatment is complicated and the purification is difficult. In the preparation, a large excess of the raw material ratio of the acetate is used, and the excess acetate is prone to ester condensation reaction under a strong basic catalyst, and a large amount of by-products are formed, which leads to difficulty in product purification.
In addition, methyl methyl cinnamate is mostly obtained by reacting p-methylbenzaldehyde with acetic anhydride or malonic acid to obtain p-methylcinnamic acid, followed by esterification with methanol to obtain methyl p-methylcinnamate. Synthetic method. Because of the existing process steps, poor production conditions, low product yield, high cost and serious pollution, it does not meet the requirements of green production.
Now, A new method for preparing 4-methyl cinnamic acid methyl ester comprises the following steps:
1) stirring and mixing with ethylene glycol dimethyl ether as a solvent and lithium diisopropylamide as a catalyst, and then stirring slowly Add p-methylbenzaldehyde dropwise, keep the temperature below 5 degree C
- After the dropwise addition, keep the reaction at 0 degree C- 10 degree C for 3-6h, slowly add 10% by mass of sulfuric acid to make The PH of the reaction solution is adjusted between 6.8 and 7.2
- The above solution is separated into an organic layer, and the solvent and excess p-methylbenzaldehyde are recovered under reduced pressure to obtain a white solid, which is washed with water and dried to give a crude product. Recrystallization from absolute ethanol gave 4-methyl cinnamic acid methyl ester.
The invention has the advantages of low raw material cost, mild reaction condition, and methyl p-methylcinnamate obtained by one-step reaction, and the method is simple, easy to operate, high in yield, stable and reliable in product quality, and non-polluting to the environment, is a kind of green The method of synthesizing fragrance.
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