9,10-dihydroergic acid(6-methylergoline-8beta-carboxylic Acid) is an important intermediate in organic synthesis, commonly used in the synthesis of compounds such as drugs and pesticides. The following are several common methods for synthesizing 9,10-dihydroergic acid in the laboratory:
1. Octadecylation reaction:
9,10-Dihydroergoline+(2E) - but-2-yne-1,4-diol+NaOH → (2E) - but-2-yne-1,4-diol-9,10-dihydroergoline+NaCl+H2O
Among them, 9,10-dihydroergic acid reacts with compounds containing (2E) - but-2-yne-1,4-diol under the action of sodium hydroxide catalyst to produce a product with specific biological activity (2E) - but-2-yne
The octyneylation reaction of 9,10-dihydroergic acid in various aspects mainly refers to the reaction of 9,10-dihydroergic acid with compounds containing octyne groups through certain chemical reactions to obtain products with specific biological activity. The octyneylation reaction usually involves the following steps:
1.1 Preparation work: Before conducting the octyneylation reaction, it is necessary to prepare the necessary 9,10-dihydroergic acid, compounds containing octyne groups, as well as necessary solvents, catalysts, etc.
1.2 Preparation of reaction solution: Dissolve 9,10-dihydroergic acid and compounds containing octanediyne groups in suitable solvents, such as common polar solvents such as DMSO, methanol, etc.
1.3 Catalyst addition: A certain amount of catalyst can be added to the reaction solution as needed to promote the reaction. Commonly used catalysts include organic bases, metal salts, etc., such as sodium hydroxide, copper chloride, etc.
1.4 Reaction temperature and time: Stir the reaction solution at a certain temperature for a period of time to ensure sufficient reaction. Normally, the reaction temperature is between room temperature and heating conditions, and the reaction time ranges from several hours to tens of hours.
1.5 Separation and Purification: After the reaction is completed, the reaction product can be separated from impurities such as catalysts through methods such as filtration and extraction. The separated product can be refined and dried to obtain a high-purity final product.
2. Erectic acid reduction method:
By reducing ergot acid with a catalyst, 9,10-dihydroergot acid can be obtained. Commonly used reducing agents include lithium metal, hydrogen gas, and catalysts (such as palladium, platinum, etc.).
The ergot acid reduction method is a method of converting 9,10-dihydroergot acid into L-ergot acid, usually using chemical reduction or biological reduction methods.
Chemical reduction method:
The chemical reduction method usually uses metal hydrides such as NaBH4 or LiAlH4 as reducing agents to reduce 9,10-dihydroergic acid to L-ergic acid. The following are the detailed steps of the chemical reduction method:
9,10-Dihydroergoline+NaBH4 → L-ergoline+NaBO2+4H2
Among them, 9,10-dihydroergic acid reacts with metal hydride NaBH4 to generate levoroergic acid and other byproducts.
(1) Dissolve 9,10-dihydroergic acid in a suitable solvent such as ethanol, methanol, ether, etc.
(2) Under nitrogen protection, metal hydrides such as NaBH4 or LiAlH4 are added to a solvent containing dissolved 9,10-dihydroergic acid.
(3) Stir the reaction at room temperature for a period of time to ensure sufficient progress of the reaction.
(4) Monitor the reaction process using thin layer chromatography (TLC) and stop stirring when the reaction approaches the endpoint.
(5) Separate and purify the product using methods such as silica gel column chromatography or crystallization.
Biological reduction method:
The bioreduction method uses microorganisms or enzymes as catalysts to reduce 9,10-dihydroergic acid to levoroergic acid. The following are the detailed steps of the bioreduction method:
9,10-Dihydroergoline+Enzyme → L-ergoline
Among them, the enzyme catalyst reduces 9,10-dihydroergic acid to L-ergic acid.
(1) Dissolve 9,10-dihydroergic acid in a suitable solvent such as water, methanol, ethanol, etc.
(2) Add an appropriate amount of microbial or enzyme catalyst to the solvent containing dissolved 9,10-dihydroergic acid.
(3) Under appropriate temperature and pH conditions, stir the reaction for a period of time to ensure the full progress of the reaction.
(4) Monitor the reaction process using thin layer chromatography (TLC) or high-performance liquid chromatography (HPLC), and stop stirring when the reaction approaches the endpoint.
(5) Separate and purify the product using methods such as silica gel column chromatography or crystallization.
3. Babulovic acid cyclization method:
This is a method of synthesizing 9,10-dihydroergic acid from Babulovic acid. Firstly, the reaction of Babulovic acid with phosphorus trichloride is used to generate derivatives of ergot acid. Subsequently, a cyclization reaction was carried out under alkaline conditions to obtain 9,10-dihydroergic acid.
The following are the detailed steps and chemical reaction equations:
9,10-Dihydroergoline+catalyst+dewatering agent → 9,10-Dihydro-8b-ergoline+by products
(1) Preparation work: Before proceeding with the synthesis of Babulovic acid ring, it is necessary to prepare the necessary 9,10-dihydroergic acid, catalysts (such as p-toluenesulfonic acid or pyridine), and dehydrating agents (such as anhydrous zinc chloride or magnesium sulfate).
(2) Preparation of reaction solution: Dissolve 9,10-dihydroergic acid and catalyst in a suitable solvent, such as dichloromethane or tetrahydrofuran. Then add a dehydrating agent to form a uniform solution.
(3) Heating reflux reaction: The prepared reaction solution is reacted in a heating reflux device. Maintain the reaction at a certain temperature for a certain time to fully proceed. The heating reflux time is usually between hours and days, and the temperature is adjusted according to specific experimental conditions.
(4) Cooling and post-treatment: After the reaction is completed, gradually cool the reaction solution to room temperature, and then proceed with post-treatment. Post treatment includes filtering to remove catalysts and dehydrating agents, washing with appropriate solvents, and finally drying to obtain Babulovic acid products.
Among them, the catalyst and dehydrating agent promote the cyclization of the carboxyl and phenyl groups of 9,10-dihydroergic acid to form Babulovic acid. The specific reaction products and by-products may vary slightly depending on the experimental conditions and the specific catalysts and dehydrating agents used.
4. Metal catalyst hydrogenation method:
By using metal catalysts (such as platinum, palladium, etc.) and hydrogen gas, the hydrogenation reaction of ergic acid can be carried out under appropriate reaction conditions to prepare 9,10-dihydroergic acid. This is a commonly used and highly selective synthesis method.
5. Other methods:
In addition to the above methods, there are also some other methods for synthesizing 9,10-dihydroergic acid, such as catalytic hydrogenation, selective reduction of reducing agents, one-step synthesis, etc.
It should be noted that when synthesizing 9,10-dihydroergic acid in the laboratory, attention should be paid to the operating conditions and safety. During the synthesis process, attention should be paid to selecting appropriate solvents, temperatures, and catalysts to ensure the efficiency and selectivity of the reaction. In addition, when conducting experiments, it is also necessary to comply with relevant safety operating regulations and measures. These are several common methods for synthesizing 9,10-dihydroergic acid in the laboratory, each with its own applicability and advantages and disadvantages. The specific method chosen should be comprehensively considered based on actual needs and conditions.