Diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate
[CAS# 1149-23-1]

Identification

• Classification: API >> Feed drug additive
• Name: Diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate
• Synonyms: 2,6-Dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine; 1,4-Dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid diethyl ester
• Molecular Formula: C₁₃H₁₉NO₄
• Molecular Weight: 253.30
• CAS Registry Number: 1149-23-1
• EC Number: 214-561-6
• SMILES: CCOC(=O)C1=C(NC(=C(C1)C(=O)OCC)C)C

Properties

• Melting point: 176-183 °C

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

Diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate, commonly known as Hantzsch esters, is an important compound in organic chemistry, known for its role in the synthesis of various pharmaceutical agents. Its unique structure and versatile reactivity have led to its widespread use in medicinal chemistry and synthetic organic chemistry.

Hantzsch esters include the synthesis of diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate, which was first reported by Arthur Hantzsch in 1881. The Hantzsch synthesis involves a multicomponent reaction between an aldehyde, a β-ketoester, and ammonia or an ammonium salt. The reaction is known for its high efficiency and simplicity, becoming one of the main methods of organic synthesis. The molecular formula of diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate is C13H19NO4. Its structural feature is that the 1,4-dihydropyridine ring is substituted by two ester groups at the 3 and 5 positions and by methyl groups at the 2 and 6 positions. This structure allows the compound to act as both a hydrogen donor and an electron-rich entity, thus facilitating a range of chemical reactions.

The most important application of diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate is in the synthesis of calcium channel blockers, which are essential for the treatment of cardiovascular diseases such as hypertension and angina pectoris. Nifedipine is a well-known calcium channel blocker and a direct derivative of the 1,4-dihydropyridine skeleton. The compound has antioxidant properties due to its ability to donate hydrogen atoms, protecting cells from oxidative stress. This property is valuable in the development of therapeutics for diseases associated with oxidative damage.

In organic synthesis, Hantzsch esters are widely used as hydride donors in reduction reactions. Its ability to selectively donate hydrogen ions makes it an essential reagent in a variety of chemical transformations, including asymmetric reductions. The compound serves as a versatile building block for the synthesis of complex molecules. Its reactivity allows for a variety of chemical modifications, enabling the creation of a wide range of compounds for research and industrial purposes.

Current research is exploring the use of diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate in the development of functional materials. Its electronic and structural properties can help design novel materials with specific optical, electronic or catalytic properties.

Ongoing research aims to further explore and expand the applications of diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate. The research focuses on optimizing its synthetic routes, improving its reactivity and selectivity, and discovering new applications in pharmaceuticals, materials science and other fields. Due to the mild reaction conditions and high efficiency of this compound, its potential in green chemistry is also being studied.

References

1966. Catalytic reduction of aromatic nitroso compounds with 2,6-dimethyl-3,5-diethoxycarbonyl-1,4-dihydropyridine. Bulletin of the Academy of Sciences of the USSR, Division of chemical science, 15(7).
DOI: 10.1007/bf00847770

1973. Oxidation of 1,4-dihydropyridines. Chemistry of Heterocyclic Compounds, 9(5).
DOI: 10.1007/bf00480581

2024. Hantzsch Synthesis of the Calcium Channel Blockers Nifedipine, Diludine, and Nitrendipine Using Methanesulfonic Acid as Catalyst. Russian Journal of Organic Chemistry, 60(6).
DOI: 10.1134/s1070428024060162