Scopolamine(Hyoscine)(link:https://www.bloomtechz.com/synthetic-chemical/api-researching-only/hyoscine-powder-cas-138-12-5.html), also known as scopolamine, is an alkaloid compound that belongs to the group of tropine alkaloids. The molecular formula is C17H21NO4, CAS 51-34-3, and the molecular weight is 303.35 g/mol. Its structure contains groups such as benzene ring, cyclohexene ring and octadienyl. It is relatively stable under neutral and weakly acidic conditions, but it will decompose under alkaline conditions. Therefore, pH control is important when preparing, storing and using Scopolamine. A range of chemical reactions can occur, including reactions such as esterification, hydrolysis, oxidation, and hydrogenation. It can react with a variety of compounds to generate different derivatives.
1. Alkaline synthesis route of Belladonna:
The method uses Belladonna (belladonna) as the starting material to synthesize Scopolamine through multi-step reactions. Firstly, the Scopolamine in Belladonna is partially extracted, and then Scopolamine is gradually synthesized through acid-base adjustment, esterification, hydrogenation and other steps.
Here are the general steps:
1.1. Extraction of Scopolamine from Belladonna:
First, the leaves and stems of the Belladonna plant are crushed and processed, and then soaked and extracted using an appropriate solvent (such as ethyl acetate, methanol, etc.) to obtain an extract containing Scopolamine.
1.2. Alkalinization adjustment:
The extract is basified, usually with a sodium hydroxide (NaOH) or potassium hydroxide (KOH) alkaline solution. This converts Scopolamine to its salt form (such as Scopolamine hydroxypyruvate).
1.3. Esterification reaction:
The alkaline-conditioned extract is reacted with a suitable acylating agent, such as acetic anhydride (Ac2O) or acetic anhydride (AcOEt), to form the esterification product of Scopolamine. This reaction is usually carried out under mild conditions.
1.4. Hydrogenation reaction:
The esterification product is subjected to hydrotreatment, using a suitable reducing agent such as hydrogen and a catalyst such as platinum or palladium to carry out a catalytic hydrogenation reaction to reduce the ester structure and generate Scopolamine.
1.5. Crystallization and purification:
Purify the desired Scopolamine product from the reaction mixture by crystallization or other purification methods.
2. Synthetic route of scopolamine method:
The method uses scopolamine as the starting material, and gradually synthesizes Scopolamine through esterification, acidification, ester hydrolysis and other reactions. Among them, the esterification step usually adopts the reaction of oxalic acid ester and scopolamine to generate oxalyl scopolamine, and then obtains Scopolamine through acidification and ester hydrolysis.
2.1. Starting material preparation:
In the scopolamine method, the starting material is scopolamine (tropic acid). Scopolamine can be extracted from certain plants, or it can be prepared through chemical synthesis.
2.2. Esterification reaction:
First, scopolamine is reacted with an appropriate alcohol to form a scopolamine product. Commonly used alcohols include methanol, ethanol, and the like. The esterification reaction is usually carried out under acidic conditions, and commonly used acid catalysts include sulfuric acid and ferrous chloride.
Example of a reaction equation:
C17H21NO4 + CH4O → methyl scopolamine + H2O
2.3. Acidification reaction:
The esterified product is acidified to convert it to the corresponding acid. Commonly used acidifying agents include sulfuric acid and ferrous chloride.
Example of a reaction equation:
Methyl scopolamine + acid → C17H21NO4 + CH4O
2.4. Ester hydrolysis:
The esters are hydrolyzed to the corresponding acids and alcohols by acid or base catalysis. In the synthesis of Scopolamine, this step allows scopolamine to react again with the alcohol formed in the previous step to synthesize Scopolamine.
Example of a reaction equation:
Methyl scopolamine + acid/base → C17H21NO + C5H12S (for recycling)
3. Synthetic route of tropic alkaloid conversion method:
The method uses other tropic alkaloids (such as atropine and atorvastatin) as starting materials, and gradually synthesizes Scopolamine through steps such as esterification, acid-base adjustment, oxidation, and acidification. The advantage of this method is that the existing tropic alkaloid structure can be used for synthesis from intermediates and the synthesis efficiency can be improved.
3.1. Starting material preparation:
In the conversion of tropic alkaloids, the starting material is usually an existing related alkaloid, such as L-hyoscyamine (levoisopropylscopolamine) or atropine (atropine). These alkaloids can be extracted from plants or prepared through chemical synthesis.
3.2. Hydrogenation reaction:
Firstly, the starting material is subjected to a hydrogenation reaction, and it is converted into different tropium alkaloids by means of hydrogenation reduction. The hydrogenation reaction is usually carried out in the presence of a catalyst, and typical catalysts include platinum or palladium and the like.
Example of a chemical reaction formula for a hydrogenation reaction:
C17H23NO3 + H2 → C17H21NO4
3.3. Structural change response:
The product of the hydrogenation reaction was further transformed by a structure change reaction to yield the target product Scopolamine. Structural change reactions typically involve acid-catalyzed or base-catalyzed cyclizations, rearrangements, or other specific reactions.
Example of a structural change response:
a) Acid-catalyzed cyclization:
C17H23NO3 → hyoscyamine ketone → C17H21NO4
b) Base-catalyzed rearrangement reactions:
C17H23NO3 → C17H21NO2 → C17H21NO4
4. Hydrogenation synthetic route:
The method uses cyclohexene thiol with tertiary amino groups as the starting material, and gradually synthesizes Scopolamine through steps such as hydrogenation, acid-base adjustment, and esterification. The key to this method is to convert cyclohexene thiol into cyclohexenamine through hydrogenation reaction, and then generate Scopolamine through esterification reaction.
4.1. Starting material preparation:
In hydrogenation, the starting material is usually an alkaloid with a similar structure, such as L-hyoscyamine (Levoisopropylscopolamine) or atropine (Atropine). These starting materials can be obtained by plant extraction or chemical synthesis.
4.2. Hydrogenation reaction:
The hydrogenation reaction is the core step of the hydrogenation method. It converts the starting material to the target product Scopolamine by hydroreduction. Hydrogenation reactions require appropriate catalysts and reaction conditions.
Example of a chemical reaction formula for a hydrogenation reaction:
a) Hydrogenation of L-hyoscyamine:
C17H23NO3 + H2 → C17H21NO4
b) Hydrogenation of Atropine:
C17H23NO3 + H2 → C17H21NO4
4.3. Separation and purification:
After the hydrogenation reaction is complete, the product is usually present along with other reactants and by-products. Therefore, isolation and purification steps are required to obtain high purity Scopolamine. Commonly used separation techniques include crystallization, solvent extraction, chromatography, and the like.
5. Photochemical synthesis route:
This method utilizes a photochemical reaction to synthesize Scopolamine. Usually, a compound with a double bond structure is used as a starting material, and a photochemical reaction occurs under light conditions, and Scopolamine is gradually synthesized through fragmentation and recombination reactions. This method is suitable for specific chemical reactions and conditions.
5.1. Overview:
Photochemical method is a method that utilizes light energy to promote chemical reactions. The electronic transitions in molecules are excited by light, and reactants in excited states are generated to participate in chemical transformations. For the photochemical synthesis of Scopolamine, excitation in the ultraviolet and visible region is usually involved.
5.2. Preparation of starting materials:
In photochemical methods, the starting material can be alkaloids with similar structures, such as L-hyoscyamine (Levoisopropylscopolamine) or atropine (Atropine). These starting materials can be obtained by plant extraction or chemical synthesis.
5.3. Photochemical reaction:
Photochemical reaction is the core step of photochemical synthesis of Scopolamine. This reaction requires an appropriate light source and reaction conditions.
Example of a chemical reaction formula for a photochemical reaction:
a) Photochemical reaction of L-hyoscyamine:
C17H23NO3 + hv → C17H21NO4
b) Photochemical reaction of Atropine:
C17H23NO3 + hv → C17H21NO4
It should be noted that hv in the above chemical reaction formula represents light energy, because the excitation process of photochemical reactions is usually represented by photon energy.
5.4. Separation and purification:
After the photochemical reaction is complete, the product usually exists along with other reactants and by-products. Therefore, suitable isolation and purification steps are required to obtain Scopolamine in high purity. Commonly used separation techniques include crystallization, solvent extraction, chromatography, and the like.
It should be noted that the above synthetic route is based on known literature and research results, and specific reaction conditions and experimental details are omitted. Synthesis of Scopolamine is a complex process involving the synthesis of multiple chemical reactions and intermediates. If you are interested in learning more about the synthetic route of Scopolamine, please refer to the relevant scientific literature or consult a professional chemist.