Epinephrine(link:https://www.bloomtechz.com/synthetic-chemical/api-researching-only/epinephrine-powder-cas-51-43-4.html) is a hormone and neurotransmitter secreted by the human body, released by the adrenal gland. It directly acts on adrenergic receptors, producing strong, rapid, and transient excitatory effects, enhancing myocardial contractility, accelerating heart rate, and increasing myocardial oxygen consumption. Epinephrine has a wide range of clinical applications, such as in cases of cardiac arrest, bronchial asthma, and allergic shock. At the same time, it can also treat urticaria, gum bleeding, and nasal mucosal bleeding. When the human body is subjected to certain stimuli such as excessive excitement, fear, and tension, adrenaline is secreted, which accelerates breathing speed, provides a large amount of oxygen to the body, accelerates blood flow and heartbeat, and dilates the pupils, providing the necessary energy for physical activity and making people react more quickly.
Common methods for synthesizing adrenaline with a single enantiomer. This method includes using α- Halogenated acetophenone serves as the starting material, and through amination and reduction reactions, a single enantiomer of adrenaline is ultimately obtained.
Step 1: Amination reaction
Firstly, the α- Halogenated acetophenones react with amines to form corresponding amide compounds. This reaction is usually carried out under alkaline conditions, such as using sodium carbonate as a catalyst. A key step in the reaction mechanism is nucleophilic addition, forming an imide intermediate.
Chemical reaction formula: R-C6H4CH (Cl) C=O+R'NH2 → R-C6H4CH (NHR ') C=O
Step 2: Reduction reaction
Next, a selective reducing agent is used to reduce the amide to generate the corresponding amino alcohol compound. Commonly used reducing agents include metal hydrides such as lithium aluminum hydride (LiAlH4) or sodium hydride (NaBH4). This reduction step causes the carbonyl group (C=O) in the amide to be reduced to hydroxyl group (- OH).
Chemical reaction formula: R-C6H4CH (NHR ') C=O+2 [H] → R-C6H4CH (NHR') CH2OH
Step 3: Chemical resolution
Finally, chemical resolution was performed to obtain a single enantiomer of adrenaline. This step is usually achieved through chiral separation, such as using methods such as chiral column chromatography, chiral ligand catalysts, or chiral derivatives. By distinguishing the physical or reactive properties of enantiomers, mixed enantiomers can be separated and the target single enantiomer of adrenaline can be obtained.
Chemical reaction formula (chiral separation): R-C6H4CH (NHR ') CH2OH → (R) - or (S) - adrenaline.
The following is a detailed route and related chemical reaction formula for preparing a single enantiomer of adrenaline using catechol and chloroacetyl chloride/chloroacetic acid as raw materials through condensation, amination, reduction, and tartaric acid resolution steps:
Step 1: Condensation reaction:
Firstly, catechins are reacted with chloroacetyl chloride or chloroacetic acid to form chloroacetyl protected catechol compounds. This condensation reaction is usually carried out under alkaline conditions, such as using triethylamine (Et3N) as a catalyst.
Chemical reaction formula: catechol+ClCH2COCl → ClCH2C (OC6H4OH) 2
Step 2: Amination reaction:
Next, the condensation product is reacted with the amine to form the corresponding amide compound. This amination reaction can be carried out under alkaline conditions to promote the nucleophilic addition of amines and generate imide intermediates.
Chemical reaction formula: ClCH2C (OC6H4OH) 2+R'NH2 → ClCH2C (OC6H4OH) 2NH-R '
Step 3: Reduction reaction:
Then, a selective reducing agent is used to reduce the amide to generate the corresponding amino alcohol compound. Commonly used reducing agents include metal hydrides, such as lithium aluminum hydride (LiAlH4) or sodium hydride (NaBH4). This reduction step causes the carbonyl group (C=O) in the amide to be reduced to hydroxyl group (- OH).
Chemical reaction formula: ClCH2C (OC6H4OH) 2NH-R '+2 [H] → ClCH2C (OC6H4OH) 2CH2NH-R'
Step 4: Tartaric acid separation:
Finally, the racemic enantiomer was separated using tartaric acid to obtain a single enantiomer of adrenaline. Tartaric acid is a chiral compound that can form crystalline salts with racemates and be separated based on optical activity.
Chemical reaction formula (resolution): ClCH2C (OC6H4OH) 2CH2NH-R '+C4H6O6 → (R) - or (S) - adrenaline+ClCH2C (OC6H4OH) 2CH2NH-R' (tartrate)
Compound a was obtained by using Xinfulin hydrochloride as the raw material and protected with boc groups under the action of an acid binding agent. Compound b was then oxidized by 2-iodobenzoic acid and reduced by sodium dithionite to obtain compound b. Compound b was then deprotected with boc protection groups by hydrochloric acid to obtain dl adrenaline like white powder. The specific steps are as follows:
Step 1: Preparation of Compound A
1. React Xinfulin hydrochloride with a binding agent to form Xinfulin binding salt.
2. Add a BOC-OSU condensation agent (such as N, N '- dipropylcarbodiimide) to react with a benzoate to generate a protected compound A.
Chemical reaction formula:
Xinfulin hydrochloride+acid binding agent → Xinfulin acid binding salt
Xinfu Linbing Salt+BOC-OSU Condensing Agent → Compound A
Step 2: Preparation of Compound B
1. Oxidize compound A with 2-iodoylbenzoic acid to generate the corresponding acid.
2. Use reducing agents such as sodium hydrosulfite (Na2S2O4) to reduce the acid and obtain compound B.
Chemical reaction formula:
Compound A+2-iodoylbenzoic acid → acid
Acid+sodium hydrosulfite → compound B
Step 3: Prepare DL adrenaline
1. Use hydrochloric acid to remove BOC protection reaction from compound B and restore the natural hydroxyl group of adrenaline.
2. After appropriate subsequent treatment and crystallization purification, DL adrenaline like white powder was obtained.
Chemical reaction formula (BOC protection removed):
Compound B+hydrochloric acid → DL adrenaline
(Note: The specific method of deprotection may vary depending on experimental conditions)