Study On Synthesis Of Albuterol Sulfate

The bronchus asthma is the most common chronic breathing problem of our times. According to a report of WHO, 1,500 million people suffer from the asthma in the whole world, which figure is still continuing increasing. For example, in Western Europe, the asthma has doubled within ten years. The American asthma patient's figure has already been more than 6 times since the early eighties. The death toll has doubled, and can be up to 5000 people every year. The global number of people dying of this disease has already exceeded 180,000 every year, and the incidence of asthma of our country is close to 1%, the specific area is up to 5%, so the asthma has already become the serious public health problem, arousing great concern from countries all over the world. In our country, asthma and high blood pressure, inferior officer of hygiene, Cardiovascular disease, the malignant tumour are together classified as the chronic disease endangering the human health seriously.Among the numerous treatments to the bronchus asthma at present, resisting the inflammation, expanding the bronchus and towning to cough are the most basic treatment methods. Albuterol sulfate is β2 excited pharmaceutical of receptor. β₂-adrenaline receptor distributes mainly onstingy way around, and the thinner the trachea, the higher density. (32 receptor excited pharmaceutical can make the bronchus smooth muscle diastolic in the smooth muscle to the bronchus. (32 receptors have very strong alternative function. Albuterol sulfate has good drug effect, and is the first-selected medicine for treating asthma and chronic of lung disease (COPD). But the study on synthesis route of the albuterol sulfate at present has such disadvantages as high cost of material, low overall yield. On the basis of typical synthesis routes in the past, this thesis regards realizing the extensive industrialization of the albuterol sulfate as the foothold, considers from different points, and tries to explore one route to be relatively less cost, high security and high overall yields.This text has discussed two different synthetic routes via salicylaldehyde and ter-butylamine as raw materials. Among them, route I is Friedel-Crafts acylation of salicylaldehyde with bromoacetyl chloride. Then the outcome reacts with ter-butylamine, while the halogen is replaced, and condensation reaction takes place, then hydrolyzes, so it becomes hydrochlorate. Carbonyl is reduced and then receives the goal result through condensation with the sulphuric acid finally. Route II is condensation reaction of salicylaldehyde with ter-butylamine first and then, Friedel-Crafts acylation, and II (2) becomes hydrochlorate by hydrochloric acid. Carbonyl is reduced and then receives the goal result through condensation with the sulphuric acid promptly. Among route II,because II (2) have activate group, it takes Friedel-Crafts acylation easily with bromineacetyl chlorine and the overall yield is relatively high. The author uses KBH4/ZnC12(mole ratio 1:1) as the reducing agent in coordination to reduce the carbonyl. It is effectual, and the yield is up to 90.5%, a little higher than that in document, while reducing the cost greatly .The overall yield of route II is slightly higher, while the overall yield is about 50% for two routes.