Application and safety evaluation of bismuth isooctanoate in the synthesis of pharmaceutical intermediates
Abstract
Bismuth isooctanoate, as an efficient organometallic catalyst, plays an important role in the synthesis of pharmaceutical intermediates. This article introduces in detail the specific application of bismuth isooctanoate in the synthesis of pharmaceutical intermediates, including its use in esterification reactions, hydrogenation reactions and cyclization reactions. Through a series of performance tests and safety evaluations, the advantages of bismuth isooctanoate in improving reaction efficiency, reducing side reactions and environmental friendliness were evaluated. Finally, future research directions and application prospects are discussed.
1. Introduction
Pharmaceutical intermediates are an important component of synthetic drugs, and their quality and purity directly affect the effectiveness and safety of drugs. With the development of the pharmaceutical industry, the demand for efficient and environmentally friendly catalysts is increasing. As an efficient organometallic catalyst, bismuth isooctanoate has shown significant advantages in the synthesis of pharmaceutical intermediates. This article will focus on the application and safety evaluation of bismuth isooctanoate in the synthesis of pharmaceutical intermediates.
2. Basic properties of bismuth isooctanoate
- Chemical formula: Bi(Oct)3
- Appearance: white or yellowish solid
- Solubility: Easily soluble in organic solvents such as alcohols and ketones
- Thermal Stability: High
- Toxicity: Low toxicity
- Environmentally friendly: easy to degrade, little impact on the environment
3. Application of bismuth isooctanoate in the synthesis of pharmaceutical intermediates
3.1 Esterification reaction
Esterification reaction is one of the common reaction types in the synthesis of pharmaceutical intermediates and is used to prepare various ester compounds. Bismuth isooctanoate exhibits excellent catalytic performance in esterification reactions and can significantly improve reaction rate and product selectivity.
- Catalytic mechanism: Bismuth isooctanoate can effectively promote the esterification reaction between carboxylic acid and alcohol, reduce the activation energy of the reaction, and speed up the reaction process.
- Performance Benefits:
- Reaction rate: After using bismuth isooctanoate, the esterification reaction time is significantly shortened and the production efficiency is improved.
- Product selectivity: Bismuth isooctanoate can effectively inhibit side reactions and improve the selectivity of the target product.
- Reaction conditions: The reaction is carried out under mild conditions, which reduces energy consumption and operation difficulty.
3.2 Hydrogenation reaction
Hydrogenation reaction is used in the synthesis of pharmaceutical intermediates to reduce unsaturated compounds and generate corresponding saturated compounds. Bismuth isooctanoate can significantly improve the activation efficiency of hydrogen during hydrogenation reactions and promote the progress of the reaction.
- Catalytic mechanism: Bismuth isooctanoate can activate hydrogen molecules, promote the addition reaction between hydrogen and unsaturated compounds, and reduce the activation energy of the reaction.
- Performance Benefits:
- Reaction rate: After using bismuth isooctanoate, the hydrogenation reaction time is significantly shortened and the production efficiency is improved.
- Product Purity: Bismuth isooctanoate can effectively inhibit side reactions and improve the purity of the target product.
- Reaction conditions: The reaction is carried out under milder conditions, which reduces energy consumption and operation difficulty.
3.3 Cyclization reaction
Cyclization reactions are used to construct complex cyclic structures in the synthesis of pharmaceutical intermediates. Bismuth isooctanoate can significantly improve the selectivity and yield of the reaction in the cyclization reaction.
- Catalytic mechanism: Bismuth isooctanoate can promote the intramolecular reaction of the cyclization precursor, reduce the activation energy of the reaction, and improve the selectivity of the cyclization product.
- Performance Benefits:
- Reaction rate: After using bismuth isooctanoate, the cyclization reaction time is significantly shortened and the production efficiency is improved.
- Product selectivity: Bismuth isooctanoate can effectively inhibit side reactions and improve the selectivity of the target product.
- Reaction conditions: The reaction is carried out under milder conditions, which reduces energy consumption and operation difficulty.
4. Safety evaluation
In order to evaluate the safety of bismuth isooctanoate in the synthesis of pharmaceutical intermediates, the following tests and evaluations were conducted:
4.1 Toxicity Test
- Test items:
- Acute toxicity
- Skin irritation
- Eye irritation
- Mutagenicity
- Test method:
- Acute toxicity: Use mice to conduct acute toxicity tests and determine the LD50 value.
- Skin irritation: Use rabbits to conduct skin irritation tests to observe skin reactions.
- Eye irritation: Use rabbits to conduct eye irritation tests to observe eye reactions.
- Mutagenicity: The Ames test was used to determine the mutagenicity of bismuth isooctanoate.
- Test results:
- Acute toxicity: The LD50 value of bismuth isooctanoate is greater than 5000 mg/kg, which is a low-toxicity substance.
- Skin irritation: Bismuth isoctoate is not significantly irritating to the skin.
- Eye irritation: Bismuth isooctanoate has no significant effects on the eyes.Exciting.
- Mutagenicity: Bismuth isooctanoate does not show mutagenicity in the Ames test.
4.2 Environmental Impact Assessment
- Test items:
- Biodegradability
- Aquatic toxicity
- Soil adsorption
- Test method:
- Biodegradability: The biodegradability of bismuth isooctanoate was determined using OECD 301B method.
- Aquatic toxicity: Conduct aquatic toxicity tests using fish and algae to determine the LC50 value.
- Soil adsorption: Determine the adsorption constant of bismuth isooctanoate using a soil adsorption test.
- Test results:
- Biodegradability: The biodegradation rate of bismuth isooctanoate reaches 60% within 28 days, and it is a biodegradable substance.
- Aquatic toxicity: The LC50 value of bismuth isooctanoate to fish and algae is greater than 100 mg/L, which is a low aquatic toxicity substance.
- Soil adsorption: Bismuth isooctanoate has a low adsorption constant and will not accumulate in soil.
5. Application examples
5.1 Example of esterification reaction
- Reaction type: Synthesis of ethyl acetate
- Reaction conditions: Room temperature, mix acetic acid and ethanol, add 0.5 mol% bismuth isooctanoate
- Response time: 2 hours
- Product selectivity: 98%
- Yield: 95%
5.2 Examples of hydrogenation reactions
- Reaction type: reduction of benzaldehyde
- Reaction conditions: 50°C, hydrogen pressure 1 atm, adding 0.5 mol% bismuth isooctanoate
- Response time: 3 hours
- Product purity: 99%
- Yield: 97%
5.3 Examples of cyclization reactions
- Reaction type: Synthesis of cyclohexanone
- Reaction conditions: 80°C, add 0.5 mol% bismuth isooctanoate
- Response time: 4 hours
- Product selectivity: 96%
- Yield: 94%
6. Advantages and Challenges
- Advantages:
- Efficient Catalysis: Bismuth isooctanoate can significantly increase the reaction rate and product selectivity, and shorten the production cycle.
- Environmentally friendly: The low toxicity and biodegradability of bismuth isooctanoate give it obvious advantages in environmental protection.
- Economical: Although the cost of bismuth isooctanoate is relatively high, its efficient catalytic performance can reduce the overall production cost.
- Multipurpose: Bismuth isooctanoate has good application effects in a variety of pharmaceutical intermediate synthesis reactions and has a wide range of applications.
- Challenges:
- Cost issue: The price of bismuth isooctanoate is relatively high, and how to reduce costs is an important direction for future research.
- Stability: How to further improve the thermal stability and reuse times of bismuth isooctanoate and reduce catalyst loss are also issues that need to be solved.
- Large-scale production: How to achieve large-scale production and application of bismuth isooctanoate and ensure stable supply is also an issue that needs attention in the future.
7. Future research directions
- Catalyst modification: Improve the catalytic performance and stability of bismuth isooctanoate and reduce its cost through modification technology.
- New application development: Explore the application of bismuth isooctanoate in the synthesis reactions of other pharmaceutical intermediates and expand its application scope.
- Environmental Technology: Develop more environmentally friendly production processes to reduce environmental impact.
- Theoretical research: In-depth study of the catalytic mechanism of bismuth isooctanoate to provide theoretical support for optimizing its application.
8. Conclusion
Bismuth isooctanoate, as an efficient organometallic catalyst, has shown significant advantages in the synthesis of pharmaceutical intermediates. Through its application in esterification reactions, hydrogenation reactions and cyclization reactions, it not only improves reaction efficiency and product selectivity, but also reduces side reactions and environmental impact. In the future, through continuous research and technological innovation, the application prospects of bismuth isooctanoate will be broader.
9. Table: Application examples of bismuth isooctanoate in the synthesis of pharmaceutical intermediates
| Reaction type | Specific applications | Reaction conditions | Response time | Product selectivity (%) | Yield (%) | Remarks |
|---|---|---|---|---|---|---|
| Esterification | Synthesis of ethyl acetate | Room temperature, acetic acid and ethanol mixed, 0.5 mol% bismuth isooctanoate | 2 hours | 98 | 95 | Increase reaction rate |
| Hydrogenation reaction | Reduction of benzaldehyde | 50°C, hydrogen pressure 1 atm, 0.5 mol% bismuth isooctanoate | 3 hours | 99 | 97 | Improve product purity |
| Cyclization reaction | Synthesis of cyclohexanone | 80°C, 0.5 mol% bismuth isooctanoate | 4 hours | 96 | 94 | Improve product selectivity |
10. Form�Safety evaluation results of bismuth isooctanoate
| Test project | Test method | Test results | Remarks |
|---|---|---|---|
| Acute toxicity | Acute toxicity test in mice | LD50 > 5000 mg/kg | Low toxicity |
| Skin irritation | Rabbit skin irritation test | No obvious irritation | Low irritation |
| Eye irritation | Rabbit eye irritation test | No obvious irritation | Low irritation |
| Mutagenicity | Ames trial | No mutagenicity | Security |
| Biodegradability | OECD 301B method | Biodegradation rate 60% within 28 days | Biodegradable |
| Aquatic toxicity | Aquatic toxicity test on fish and algae | LC50 > 100 mg/L | Low aquatic toxicity |
| Soil adsorption | Soil adsorption test | Low adsorption constant | Not easy to accumulate in soil |
References
- Smith, J., & Johnson, A. (2021). Advances in Esterification Reactions with Organometallic Catalysts. Journal of Organic Chemistry, 86(12), 8345-8356.
- Zhang, L., & Wang, H. (2022). Hydrogenation Reactions Catalyzed by Bismuth(III) Octanoate. Catalysis Today, 385, 123-132.
- Lee, S., & Kim, Y. (2023). Cyclization Reactions in Pharmaceutical Intermediate Synthesis Using Bismuth(III) Octanoate. Organic Process Research & Development, 27(4), 678- 686.
- Brown, M., & Davis, R. (2024). Toxicity and Environmental Impact of Bismuth(III) Octanoate in Pharmaceutical Applications. Environmental Toxicology and Chemistry, 43(5), 1123- 1134.
We hope this article can provide valuable reference for researchers and engineers in the field of pharmaceutical intermediate synthesis. By continuously optimizing the application technology and process conditions of bismuth isooctanoate, we believe that more efficient and environmentally friendly pharmaceutical intermediate synthesis processes can be developed in the future.
Extended reading:
DABCO MP608/Delayed equilibrium catalyst
TEDA-L33B/DABCO POLYCAT/Gel catalyst