5-Bromopyrimidine-2-carbonitrile
[CAS# 38275-57-9]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Cyanopyrimidine
• Name: 5-Bromopyrimidine-2-carbonitrile
• Molecular Formula: C₅H₂BrN₃
• Molecular Weight: 183.99
• CAS Registry Number: 38275-57-9
• EC Number: 691-026-7
• SMILES: C1=C(C=NC(=N1)C#N)Br

Properties

• Density: 1.9±0.1 g/cm³ Calc.^*
• Boiling point: 317.7±34.0 °C 760 mmHg (Calc.)^*
• Flash point: 145.9±25.7 °C (Calc.)^*
• Index of refraction: 1.618 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS05;GHS07;GHS09 Danger
• Risk Statements: H302+H312+H332-H302-H312-H315-H318-H319-H332-H335-H400-H410
• Safety Statements: P261-P264-P264+P265-P270-P271-P273-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P305+P354+P338-P317-P319-P321-P330-P332+P317-P337+P317-P362+P364-P391-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	H312
Acute toxicity	Acute Tox.	4	H302
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	4	H332

Discovery and Applications

5-Bromopyrimidine-2-carbonitrile is a halogenated, nitrogen-containing heteroaromatic compound consisting of a pyrimidine ring bearing a bromine atom at position 5 and a nitrile group at position 2. Its molecular formula is C₅H₂BrN₃, and its molecular weight is approximately 199.00 g/mol. The presence of both a halogen substituent and a cyano functional group on the aromatic ring has a significant influence on its electronic character, reactivity, and synthetic utility. The pyrimidine core is electron deficient due to the two ring nitrogens and the nitrile substituent, and the bromine atom serves as a synthetically versatile functional handle.

The compound is commonly obtained through halogenation of appropriately substituted pyrimidine intermediates or through stepwise assembly of the heterocycle followed by selective introduction of the cyano and bromo substituents. One approach involves nucleophilic substitution on a prefunctionalized 5-halo pyrimidine precursor by a cyanide source to form the nitrile at position 2, followed by purification and crystallization. Alternatively, multistep heterocycle construction strategies assemble the pyrimidine core via condensation of suitable carbonyl and amidine derivatives, after which bromination yields the desired substitution pattern. Reaction conditions are typically optimized to preserve the integrity of the nitrile function and avoid undesired substitution or ring-opening pathways.

From a chemical reactivity perspective, the bromine atom at position 5 provides access to a broad range of substitution and coupling transformations. It can participate in nucleophilic aromatic substitution reactions under appropriate conditions, enabling replacement with amines, thiols, or other nucleophiles. It can also be used in palladium-catalyzed cross-coupling reactions such as Suzuki, Sonogashira, Buchwald–Hartwig, and Stille couplings, facilitating attachment of aryl, alkyl, alkenyl, or heteroatom substituents to the pyrimidine ring. The nitrile group is comparatively robust, yet can undergo typical cyano-group reactions including hydrolysis to the corresponding amide or carboxylic acid, or conversion to amidines under controlled conditions. Together, these two substituents create a platform for diverse transformations, making the compound a flexible intermediate for producing structurally varied derivatives.

In terms of physical properties, 5-bromopyrimidine-2-carbonitrile is typically a crystalline solid at room temperature. It shows solubility in organic solvents such as dimethylformamide, dimethyl sulfoxide, acetone, and dichloromethane, while displaying limited solubility in water. Its stability under ambient storage conditions is generally good, though exposure to strong bases, strong acids, or high temperatures can promote decomposition, hydrolysis of the nitrile group, or substitution of the bromine atom. The aromatic and heterocyclic nature of the compound contributes to its rigidity, and the electron-withdrawing nitrile group often influences crystallization behavior and spectroscopic characteristics.

The compound is used primarily as a synthetic intermediate in heterocyclic and medicinal chemistry. Its substitution pattern allows rapid access to libraries of functionalized pyrimidines, which are widely explored for applications in pharmaceutical research, agrochemical development, and biochemical probe design. The pyrimidine core is a privileged scaffold in molecule development programs, and the ability to selectively modify either the bromine position or the nitrile group allows systematic study of structure–reactivity and structure–function relationships. Its defined geometry and predictable reactivity render it a starting point for the synthesis of heterocycle-rich frameworks, fused ring systems, and diverse analogues.

Overall, 5-bromopyrimidine-2-carbonitrile combines a synthetically reactive halogen, a stable nitrile group, and an electron-deficient heteroaromatic system. These structural features enable selective functionalization and controlled derivatization, supporting its role as a useful intermediate for preparing more complex nitrogen-containing compounds and for advancing research in chemical synthesis and molecular design.

References

2023. Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors. Science, 382(6671).
DOI: 10.1126/science.abo7201