2-Aminomethylpyrazine
[CAS# 20010-99-5]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrazines
• Name: 2-Aminomethylpyrazine
• Molecular Formula: C₅H₇N₃
• Molecular Weight: 109.13
• CAS Registry Number: 20010-99-5
• EC Number: 690-477-7
• SMILES: C1=CN=C(C=N1)CN

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 207.5±25.0 °C 760 mmHg (Calc.)^*, 117 - 118 °C (Expl.)
• Flash point: 101.3±10.4 °C (Calc.)^*
• Index of refraction: 1.558 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS05;GHS06;GHS07 Danger
• Risk Statements: H301-H302-H314-H315-H318-H335
• Safety Statements: P260-P261-P264-P264+P265-P270-P271-P280-P301+P316-P301+P317-P301+P330+P331-P302+P352-P302+P361+P354-P304+P340-P305+P354+P338-P316-P317-P319-P321-P330-P332+P317-P362+P364-P363-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Skin corrosion	Skin Corr.	1B	H314
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Serious eye damage	Eye Dam.	1	H318
Acute toxicity	Acute Tox.	3	H301

Discovery and Applications

2-Aminomethylpyrazine is a heterocyclic organic compound consisting of a pyrazine ring substituted with a primary aminomethyl group at position 2 of the ring framework. Its molecular formula is C₅H₇N₃, and its structure contains a six‑membered aromatic ring incorporating two nitrogen atoms located at the 1‑ and 4‑positions. The presence of an aminomethyl group attached directly to the aromatic heterocycle introduces both basicity and enhanced nucleophilicity relative to unsubstituted pyrazine. In addition, the molecule displays greater polarity and hydrogen‑bonding capacity than many other monosubstituted pyrazines, while retaining the characteristic aromatic stability of the pyrazine system.

From a structural perspective, 2‑aminomethylpyrazine may be described as a member of the substituted pyrazines often examined for their electronic properties and chemical reactivity. The two ring nitrogen atoms lower the electron density of the aromatic system, producing a heteroaromatic scaffold that is less reactive toward electrophilic substitution than benzene, but more susceptible to nucleophilic attack in specific substitution patterns. Incorporation of an aminomethyl substituent modifies the electronic distribution in the vicinity of the ring and allows for intramolecular interactions between the amine lone pair and the heterocyclic nitrogen atoms.

The compound is generally obtained through the functionalization of pyrazine derivatives bearing an appropriate leaving group at the 2‑position, followed by conversion into the aminomethyl substituent. Because the aminomethyl group contains a primary amine, the compound is commonly handled as a salt to ensure stability and ease of purification, although it can also be isolated and stored in its free base form under suitable conditions. When pure, 2‑aminomethylpyrazine is typically encountered as a crystalline or low‑melting solid with noticeable hygroscopic tendencies due to the basic amino group, and it demonstrates solubility in polar solvents, including lower alcohols and water.

The aminomethyl group plays a central role in determining the chemical behavior of the compound. It is capable of engaging in acid–base reactions, most notably protonation to form an ammonium salt. The primary amine functionality lends itself to further functional derivatization, including acylation, alkylation, and condensation, permitting the generation of structurally diverse derivatives while maintaining the integrity of the heteroaromatic core. The pyrazine moiety, in turn, presents opportunities for controlled substitution at other positions of the ring once the reactivity of the amino function has been moderated or selectively protected.

In chemical research, 2‑aminomethylpyrazine is often regarded as a versatile intermediate due to this combination of a reactive amine and a stable aromatic heterocycle. It can be converted into a wide range of derivatives through modifications centered at either the amino group or the ring, enabling the preparation of compounds designed for analytical studies, coordination chemistry, or functional group transformation sequences. The aminomethyl side chain provides an accessible site for attachment to larger molecules or materials, while the pyrazine nucleus provides a rigid and electronically distinctive platform.

In terms of physicochemical characteristics, the compound displays behavior typical of small, nitrogen‑rich heterocycles. It has a measurable basic dissociation constant associated with protonation of the amino group, while the heteroaromatic ring itself is only weakly basic. The molecule is capable of acting as both a hydrogen‑bond donor and acceptor, which influences solubility, crystallization tendencies, and interactions with other molecular species. Controlled storage conditions that limit moisture exposure are recommended to prevent gradual changes associated with hygroscopic uptake.

The combination of a primary amine and a pyrazine core defines the practical value of 2‑aminomethylpyrazine in laboratory settings. Its stability, ease of handling, and capacity for selective functionalization allow the molecule to serve as a useful starting point for preparing structurally related heterocycles or for generating derivatives in which the amino functionality plays a central role. By maintaining a balance between aromatic stability and reactive potential, the compound supports a range of transformations in which structural precision and controlled substitution are required.

References

2021. Self-assembly of Pd4L2 Supramolecular Cage and Permanganate Anion Adsorption Behavior in Water. Journal of Cluster Science.
DOI: 10.1007/s10876-021-02173-7

2002. Ring Closure of 2-(Aminoalkyl)pyrazines using Carbon Disulfide. Science of Synthesis.
URL: SD-012-00833