Methyl (Z)-3-aminocrotonate
[CAS 21731-17-9]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Carboxylic esters and their derivatives
• Name: Methyl (Z)-3-aminocrotonate
• Synonyms: Methyl (2Z)-3-amino-2-butenoate
• Molecular Formula: C₅H₉NO₂
• Molecular Weight: 115.13
• CAS Registry Number: 21731-17-9
• EC Number: 244-549-6
• SMILES: C/C(=C/C(=O)OC)/N

Properties

• Solubility: Soluble (56 g/L) (25 °C), Calc.^*
• Density: 1.031±0.06 g/cm³ (20 °C 760 Torr), Calc.^*
• Melting point: 81 - 84 °C (Expl.)
• Boiling point: 194.1±13.0 °C 760 mmHg (Calc.)^*, 229.7 °C (Expl.)
• Flash point: 65.3±17.4 °C (Calc.)^*, 91 °C (Expl.)
• Index of refraction: 1.457 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS05;GHS06;GHS07 Danger
• Risk Statements: H302-H317-H318-H319-H330
• Safety Statements: P260-P261-P264-P264+P265-P270-P271-P272-P280-P284-P301+P317-P302+P352-P304+P340-P305+P351+P338-P305+P354+P338-P316-P317-P320-P321-P330-P333+P317-P337+P317-P362+P364-P403+P233-P405-P501

chemBlink Chemical Story

Methyl (Z)-3-aminocrotonate, CAS 21731-17-9, is an enamine ester used primarily as a synthetic intermediate in organic and medicinal chemistry. It is also known as methyl (Z)-3-aminobut-2-enoate and has the molecular formula C₅H₉NO₂ and a molecular weight of 115.13. Its structure combines an amino group, a carbon-carbon double bond, and a methyl ester within a short four-carbon chain. This arrangement gives the molecule characteristics of both an enamine and an α,β-unsaturated ester, making it a useful precursor for constructing nitrogen-containing heterocycles.

The Z designation describes the geometry around the carbon-carbon double bond. In Methyl (Z)-3-aminocrotonate, the higher-priority substituents on the alkene are arranged on the same side according to the Cahn-Ingold-Prelog convention. This stereochemical detail is important because enamines can exist as different geometric isomers, and their reactivity, hydrogen bonding, and conformational preferences can depend on that arrangement.

One of the most useful features of this compound is the combination of nucleophilic and electrophilic character within the same small molecule. The amino-substituted alkene behaves as an enamine, meaning that electron density is available at the carbon-carbon double bond through conjugation with nitrogen. At the same time, the ester carbonyl creates an electron-withdrawing region. This internal electronic contrast makes the molecule well suited to condensation and cyclization reactions.

Enaminones and related β-amino unsaturated carbonyl compounds are widely used as intermediates for heterocycle synthesis. Their preorganized carbon, nitrogen, and carbonyl functionality allows them to react with amidines, guanidines, hydrazines, ureas, and other bifunctional nucleophiles to form rings such as pyrimidines, pyrazoles, and related nitrogen heterocycles. Methyl (Z)-3-aminocrotonate belongs to this broader family of versatile heterocyclic precursors.

A classic application is the synthesis of substituted pyrimidines. Pyrimidine rings contain two nitrogen atoms in a six-membered aromatic ring and occur in nucleic-acid bases, pharmaceuticals, agrochemicals, and many biologically active compounds. In a typical cyclocondensation, the enamine ester contributes a carbon framework while a nitrogen-rich reagent supplies additional nitrogen atoms. New bonds form, small molecules are eliminated, and the initially open-chain precursor is converted into an aromatic heterocycle.

This strategy is attractive because much of the substitution pattern can be programmed into the starting materials. The methyl group already present on Methyl (Z)-3-aminocrotonate can become a substituent on the final heterocycle, while the ester-derived carbonyl contributes to ring construction. By changing the nitrogen-containing reaction partner, chemists can generate a family of differently substituted heterocycles from the same enamine ester.

The molecule has therefore appeared in pharmaceutical synthesis as an upstream intermediate rather than as an active drug itself. Published patent and medicinal-chemistry literature use methyl 3-aminocrotonate in the preparation of substituted pyrimidines and related heteroaromatic systems that are subsequently elaborated into more complex biologically active molecules. This is an important distinction: the biological properties belong to the final heterocycle or drug candidate, not to CAS 21731-17-9 simply because it contributed atoms to the synthesis.

Its chemistry also illustrates why enamines are so valuable. Carbonyl compounds normally react at the carbonyl carbon, but conversion to an enamine changes the distribution of electron density and can make a neighboring carbon nucleophilic. Chemists can therefore use enamines as controlled carbon nucleophiles in bond-forming reactions. In Methyl (Z)-3-aminocrotonate, this enamine character is combined with an ester group, providing both reactivity and a convenient handle for ring formation.

The amino group itself can participate in hydrogen bonding and tautomeric equilibria. The molecule may be described by resonance and tautomeric structures in which electron density is shared between nitrogen and the adjacent double bond. These electronic effects help explain why simple structural formulas can underestimate the flexibility of enamine chemistry.

Methyl 3-aminocrotonate can be prepared from methyl acetoacetate through reaction with ammonia or ammonia equivalents. Methyl acetoacetate is a β-keto ester, and replacing the keto oxygen functionality by an amino-substituted alkene gives the corresponding enamine ester. This transformation is a familiar example of how carbonyl compounds can be converted into nitrogen-containing synthetic intermediates with very different reactivity.

The compound also demonstrates molecular economy. With only five carbon atoms, it already contains the carbon framework, nitrogen atom, alkene geometry, and ester functionality needed for several subsequent transformations. Rather than assembling every heterocycle atom by atom, chemists can begin with a small preorganized precursor in which several future ring atoms and substituents are already correctly positioned.

This is why Methyl (Z)-3-aminocrotonate is best understood as a heterocycle-building reagent. Its importance lies not in a famous final use of its own, but in the way it condenses chemical information into a small structure. The amino group, double bond, ester, and methyl substituent together create a molecular starting point from which much more elaborate nitrogen heterocycles can emerge.

Modern medicinal chemistry depends heavily on such intermediates. A complex drug may contain a pyrimidine or another nitrogen heterocycle that appears highly sophisticated in the final structure, but the ring can often trace its origin to a surprisingly small reagent. Methyl (Z)-3-aminocrotonate is one example of how a simple open-chain molecule can be designed to fold, condense, and reorganize into the rigid heterocyclic frameworks that are so common in bioactive chemistry.

References

1. PubChem. Methyl 3-aminocrotonate. CAS 21731-17-9. Chemical identity and molecular information.

2. Joule, J. A.; Mills, K. (2010). Heterocyclic Chemistry, 5th ed. Wiley. Synthetic chemistry of enamines and pyrimidine-forming cyclocondensations.

3. Katritzky, A. R.; Ramsden, C. A.; Joule, J. A.; Zhdankin, V. V. (2010). Handbook of Heterocyclic Chemistry, 3rd ed. Elsevier. Enamine and β-aminocarbonyl precursors in heterocycle synthesis.

4. Comprehensive Organic Synthesis literature describing methyl 3-aminocrotonate as a precursor for substituted pyrimidines and related nitrogen heterocycles.

5. Commercial and patent synthesis records for CAS 21731-17-9 describing pharmaceutical-intermediate applications.