2-Amino-4-chloropyrimidine
[CAS# 3993-78-0]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Chloropyrimidine
• Name: 2-Amino-4-chloropyrimidine
• Molecular Formula: C₄H₄ClN₃
• Molecular Weight: 129.55
• CAS Registry Number: 3993-78-0
• EC Number: 627-726-6
• SMILES: C1=CN=C(N=C1Cl)N

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Melting point: 155 - 160 ºC (Decomposes) (Expl.)
• Boiling point: 314.6±34.0 ºC 760 mmHg (Calc.)^*
• Flash point: 144.1±25.7 ºC (Calc.)^*
• Index of refraction: 1.618 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Hazard Statements: H302-H315-H318-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P354+P338-P317-P319-P321-P330-P332+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
Acute toxicity	Acute Tox.	4	H302
Serious eye damage	Eye Dam.	1	H318
Eye irritation	Eye Irrit.	2	H319

Discovory and Applicatios

2-Amino-4-chloropyrimidine is a nitrogen-containing heteroaromatic compound in which a pyrimidine ring is substituted with an amino group at position 2 and a chlorine atom at position 4. Its molecular formula is C₄H₄ClN₃, with a molecular weight of approximately 127.55 g/mol. The pyrimidine ring, containing two nitrogen atoms at positions 1 and 3, is electron-deficient, and the substitution pattern introduces distinct electronic and steric properties that influence reactivity. The amino group is nucleophilic and capable of hydrogen bonding, whereas the chloro group serves as a reactive site for nucleophilic substitution.

Synthesis of 2-amino-4-chloropyrimidine typically involves selective halogenation of 2-aminopyrimidine or nucleophilic substitution on pre-halogenated pyrimidine intermediates. One common approach is the chlorination of 2-aminopyrimidine under controlled conditions to achieve substitution at the 4-position without affecting the amino group. Alternative strategies involve condensation of suitably substituted β-dicarbonyl compounds or amidines to form the pyrimidine ring, followed by introduction of the chloro group through electrophilic chlorination. Reaction conditions are carefully optimized to maintain regioselectivity and prevent overhalogenation or decomposition of sensitive functional groups.

Chemically, the amino group at position 2 can undergo acylation, alkylation, or condensation reactions, allowing the formation of amides, Schiff bases, or other nitrogen-containing derivatives. The chlorine atom at position 4 is susceptible to nucleophilic aromatic substitution with amines, thiols, or alkoxides, enabling the construction of a diverse array of substituted pyrimidines. The electron-deficient nature of the pyrimidine ring also facilitates selective functionalization at other positions when further activated or derivatized.

2-Amino-4-chloropyrimidine is generally a solid at room temperature and shows solubility in polar organic solvents such as dimethylformamide, ethanol, and acetone. It is chemically stable under ambient conditions but should be protected from strong oxidizing agents or bases that could decompose the amino or chloro functionalities. The combination of a nucleophilic amino group and an electrophilic chloro group provides multiple synthetic handles for the preparation of complex heteroaromatic compounds.

In practical applications, 2-amino-4-chloropyrimidine is widely used as a building block in medicinal chemistry, agrochemical synthesis, and heterocyclic chemistry. Its defined substitution pattern enables the preparation of functionalized pyrimidines through selective substitution and derivatization, facilitating the development of biologically active molecules, enzyme inhibitors, and other heterocyclic scaffolds. The amino and chloro groups provide complementary reactivity that allows systematic exploration of structure–activity relationships in synthetic and biological studies.

Overall, 2-amino-4-chloropyrimidine combines a reactive amino group, an electrophilic chloro substituent, and an electron-deficient pyrimidine ring, making it a versatile intermediate in heterocyclic synthesis. Its predictable reactivity and structural features enable selective functionalization and the construction of diverse nitrogen-containing compounds for chemical and pharmaceutical applications.

References

2024. Synthetic account on indoles and their analogues as potential anti-plasmodial agents. Molecular Diversity.
DOI: 10.1007/s11030-024-10842-8

2021. Priority directions in the design of biologically active compounds based on 2-aminopyrimidin-4(3H)-one and its derivatives. Chemistry of Heterocyclic Compounds, 57(2).
DOI: 10.1007/s10593-021-02875-w

2016. Oxyfunctionalization of pyridine derivatives using whole cells of Burkholderia sp. MAK1. Scientific Reports, 6.
DOI: 10.1038/srep39129