Alpha-methylcinnamaldehyde

Alpha-methylcinnamaldehyde also named as alpha-methyl cinnamaldehyde, is a yellow liquid with a cinnamon aroma, soluble in ethanol, propylene glycol and non-volatile oils, insoluble in glycerin and water. It is a widely used synthetic essence and an important fine chemical intermediate, commonly used in the fragrance of cosmetics, soaps, foods, drugs and so on. The alpha-methyl streptopropane obtained by the further reaction thereof is used as a spice and also has a very good aroma. At the same time, alpha-methylcinnamaldehyde is also an important intermediate for the synthesis of the therapeutic drug epalrestat. As the number of diabetic patients increases, the demand for the drug increases, and the demand for intermediates also increases.

Epalrestat can be used to prevent, ameliorate and treat peripheral neuropathy (numbness, pain) associated with diabetes, an aldose reductase inhibitor, and reversibly inhibit glucose metabolism in polyol metabolism associated with the pathogenesis of diabetic complications. It is converted into an aldose reductase of sorbitol, which is known to affect the function of nerve cells. It accumulates in neurons and causes symptoms of peripheral neuropathy that dictate the sensory movement of diabetes. Abnormal vibrational sensation and abnormal heartbeat (showing a high glycosylated hemoglobin value).

Attentions:

(1) For diabetic patients with diet therapy, exercise therapy, oral hypoglycemic agents or insulin therapy with high glycosylated hemoglobin values. Patients with diabetic peripheral neuropathy with irreversible organic changes are not sure of their effects. When the drug is ineffective for 12 weeks, it should be treated with other methods.

(2) After taking this product, the urine is yellowish brown, which will affect the qualitative test of erythropoietin and ketone body urine. Occasionally, creatinine, bilirubin and aminotransferase are elevated, in addition, erythema, blisters and other symptoms may occur, and should be discontinued and disposed of properly. Pregnant and lactating women are hanged. Oral: Adult 50mg once before meals, 3 times a day. Appropriate increase or decrease with age and symptoms.

(3) After taking this product, the urine is yellowish brown, which will affect the qualitative test of bilirubin and ketone body urine.

(4) occasionally elevated creatinine, bilirubin and aminotransferase, in addition, erythema, blisters and other symptoms may occur, should be discontinued and appropriate disposal.

(5) Not available for pregnant and lactating women.

The object of the present invention is to provide a preparation method of alpha-methylcinnamaldehyde, which comprises synthesizing alpha-methyl cinnamon with benzaldehyde and n-propionaldehyde in an alkaline medium and using an aqueous solution of methanol as a solvent. Aldehyde, simple method, convenient operation, low raw material cost, high yield, no pollution to the environment, very suitable for industrial production.

Improve diabetes after meals, hyperglycemia (this product is only suitable for patients who receive diet therapy, exercise therapy has not achieved significant results, or patients with oral hypoglycemic drugs or insulin preparations in addition to diet therapy, exercise therapy without significant results). Patients with severe ketosis, diabetic coma or coma, severe infection, pre- and post-operative, severe trauma. Adrenalin, adrenocortical hormone, and thyroid hormone can reduce the hypoglycemic effect of diabetes drugs. Beta-blockers, salicylic acid preparations, monoamine oxidase inhibitors, clofibrate hyperlipidemia therapeutics, warfarin can enhance the blood sugar lowering effect of diabetes drugs.

At present, the major laboratories mainly synthesize alpha-methylcinnamaldehyde from benzaldehyde and butyraldehyde. The amount of catalyst, molar ratio of raw materials and reaction time have great influence on the yield of alpha-methylcinnamaldehyde. The optimized conditions are as follows: ethanol as solvent, tetrabutylammonium bromide as catalyst, n (benzaldehyde): n (propionaldehyde): n (catalyst) 1.4:1:0.015, reaction at room temperature for 6 hours, yield up to 84.6%, an excess of benzaldehyde can be recovered.

Some other methods of synthesizing alpha-methyl cinnamaldehyde are as follows:

1. Using benzaldehyde and n-propionaldehyde as raw materials, KF/A1203 as catalyst, polyethylene glycol as phase transfer solution, and synthesis of ct-methyl cinnamaldehyde, the yield was 78.9%. The yield of alpha-methylcinnamaldehyde synthesized by the method is high, and the process is relatively simple, but the preparation of the catalyst used is complicated, expensive, and has a little pollution to the environment, and the recycling process is cumbersome.

2. Using benzaldehyde and n-propionaldehyde as raw materials, ethanol as solvent, PEG400 and PEG600 as phase transfer to synthesize alpha-methylcinnamaldehyde, the yield is 54.2%. The alpha-methylcinnamaldehyde synthesized by this method has more negative reaction and product separation. It is difficult to purify.

3. Using benzaldehyde and n-propanal as raw materials, ethanol as solvent, TBAB as phase transfer catalyst, synthesizing a-methyl cinnamaldehyde under alkaline medium, the yield is 59.7%. The alpha-methyl cinnamaldehyde synthesized by this method The synthesis process is simple, but the conversion rate of the raw material reaction is low, and the negative reaction is high, resulting in a low product yield. 

Potential health effects:

     Inhalation May be harmful if inhaled. May cause respiratory irritation.

     Ingestion is harmful if taken.

     Skin absorption through the skin can be harmful. May cause skin irritation.

     Eyes may cause eye irritation.