Ethyl 3-amino-4,4,4-trifluorocrotonate
[CAS# 107638-19-7]

Identification

• Classification: Flavors and spices >> Synthetic spice >> Carboxylic acid and ester perfume >> Aliphatic carboxylate
• Name: Ethyl 3-amino-4,4,4-trifluorocrotonate
• Synonyms: methyl (Z)-3-amino-4,4,4-trifluorobut-2-enoate
• Molecular Formula: C₆H₈F₃NO₂
• Molecular Weight: 183.13
• CAS Registry Number: 107638-19-7
• SMILES: COC(=O)/C=C(/C(F)(F)F)\N

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Boiling point: 208.3±40.0 ºC 760 mmHg (Calc.)^*
• Flash point: 79.8±27.3 ºC (Calc.)^*
• Index of refraction: 1.398 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovory and Applicatios

Ethyl 3-amino-4,4,4-trifluorocrotonate is a fluorinated amino ester that has attracted attention because of its utility as a synthetic intermediate in the preparation of biologically active molecules. The compound combines an amino substituent on a conjugated ester backbone with a trifluoromethyl group that contributes unique electronic and steric properties. Its discovery was associated with research into new methods for introducing fluorine into organic frameworks, particularly in the context of heterocyclic and pharmaceutical chemistry. Fluorine-containing groups have long been studied for their ability to modify lipophilicity, metabolic stability, and binding affinity in drug molecules, and the synthesis of ethyl 3-amino-4,4,4-trifluorocrotonate represented a contribution to this area of investigation. The preparation of this compound has been reported in the literature through condensation reactions involving fluorinated intermediates that introduce the trifluoromethyl group into the crotonate framework, followed by amination. Researchers established practical procedures to obtain the compound in laboratory settings, which allowed its further evaluation as a building block.

The importance of ethyl 3-amino-4,4,4-trifluorocrotonate lies in its role as a versatile precursor. The trifluoromethylated double bond system provides a reactive platform for transformations, while the amino group makes it suitable for derivatization into a wide range of products. Applications have been documented in the synthesis of trifluoromethyl-substituted heterocycles such as pyridines and pyrazoles, where the compound serves as a starting point for cyclization reactions. These heterocycles are of great relevance in medicinal chemistry because the introduction of fluorine often enhances biological activity. The compound has also been used in the synthesis of amino acid analogues that incorporate a trifluoromethyl group, providing modified building blocks for peptide chemistry. Such analogues are of interest because the presence of fluorine can alter hydrogen-bonding patterns and enzyme interactions, which is significant in the design of enzyme inhibitors and receptor ligands.

In addition to heterocyclic synthesis, ethyl 3-amino-4,4,4-trifluorocrotonate has been employed in transformations that lead to agrochemicals. The electron-withdrawing character of the trifluoromethyl group modifies the reactivity of the conjugated ester, facilitating selective reactions that can be exploited in the preparation of crop protection agents. Studies in this area have highlighted the growing importance of fluorinated synthons as components in agrochemical research, where metabolic stability and environmental persistence are key considerations. The compound has also served as a reagent in the preparation of specialty materials where fluorine contributes to chemical resistance and altered surface properties.

The discovery and subsequent applications of ethyl 3-amino-4,4,4-trifluorocrotonate reflect broader trends in fluorine chemistry. Since the mid-twentieth century, chemists have explored the introduction of fluorine into small organic molecules as a strategy for fine-tuning physical and biological properties. The development of synthetic routes to this compound expanded the library of fluorinated building blocks available to medicinal and materials chemists. Its use in creating heterocycles, amino acid analogues, and agrochemical intermediates demonstrates the versatility of the scaffold. As research into fluorine-containing molecules continues to grow, ethyl 3-amino-4,4,4-trifluorocrotonate remains a valuable example of how targeted molecular design can provide practical tools for applications across pharmaceutical, agricultural, and industrial fields.

References

2023. Method for preparing intermediate of uracil compound containing isoxazoline. US Patent, US-2023265084-A1.
Priority Date: 2020-07-02

2023. Method for preparing isoxazoline-containing uracil compound intermediates. European Patent, EP-4177251-A1.
Priority Date: 2020-07-02

2003. Substituted phenyluracils. US Patent, US-6649760-B2.
Grant Date: 2003-11-18