2-[(6-Chloro-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl)methyl]benzonitrile
[CAS 865758-96-9]

Identification

• Classification: Organic raw materials >> Nitrile compound
• Name: 2-[(6-Chloro-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl)methyl]benzonitrile
• Molecular Formula: C₁₃H₁₀ClN₃O₂
• Molecular Weight: 275.69
• CAS Registry Number: 865758-96-9
• EC Number: 695-742-0
• SMILES: CN1C(=O)C=C(N(C1=O)CC2=CC=CC=C2C#N)Cl

Properties

• Density: 1.4±0.1 g/cm³ Calc.^*
• Boiling point: 418.0±55.0 °C 760 mmHg (Calc.)^*
• Flash point: 206.6±31.5 °C (Calc.)^*
• Index of refraction: 1.647 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H317
• Safety Statements: P261-P272-P280-P302+P352-P321-P333+P317-P362+P364-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin sensitization	Skin Sens.	1	H317

Discovery and Applications

2-[(6-Chloro-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl)methyl]benzonitrile is a synthetic heterocyclic compound consisting of a substituted pyrimidinedione (uracil-like) core linked via a methylene bridge to a benzonitrile aromatic system. The molecule belongs to the broader class of functionalized pyrimidines, which are structurally related to nucleobase analogs.

The central heterocyclic portion is a 3,4-dihydro-2,4-dioxo-1(2H)-pyrimidine ring, which is closely related to uracil derivatives. This six-membered ring contains two nitrogen atoms and two carbonyl groups at the 2 and 4 positions. These carbonyl groups are strongly electron-withdrawing and participate in resonance stabilization of the heterocycle, giving the system a polarized and partially aromatic character.

At the 6-position of the pyrimidine ring, a chlorine atom is present. This halogen substituent exerts a strong inductive electron-withdrawing effect, increasing the electrophilicity of the heterocycle and influencing its reactivity toward nucleophiles. The C–Cl bond at this position is also a potential site for substitution reactions under appropriate synthetic conditions.

At the 3-position of the pyrimidine ring, there is a methyl group. This substituent slightly increases electron density through inductive donation and also introduces steric bulk that can influence the overall conformation and intermolecular interactions of the molecule. The N-methyl substitution at position 3 also reduces hydrogen-bond donating ability compared with unsubstituted uracil analogs.

The pyrimidinedione ring is connected through a methylene (-CH2-) linker to a benzonitrile group at the ortho position. This linker provides flexibility between the two aromatic systems, allowing rotational freedom and reducing direct electronic conjugation between them.

The benzonitrile moiety consists of a benzene ring substituted with a nitrile group (–C≡N). The nitrile group is strongly electron-withdrawing due to the high electronegativity of nitrogen and the sp-hybridized carbon. This functional group increases the polarity of the aromatic ring and serves as a hydrogen bond acceptor in intermolecular interactions.

Structurally, the molecule contains two distinct electronic domains: the electron-deficient pyrimidinedione core and the nitrile-substituted benzene ring. These are connected by a saturated methylene linker, which limits conjugation and results in relatively independent electronic behavior of each moiety.

The pyrimidinedione ring is largely planar due to conjugation between the carbonyl groups and the ring nitrogen atoms. This planarity supports resonance stabilization and influences hydrogen bonding capability. In contrast, the benzonitrile ring is also planar, but the overall molecule is not fully rigid due to the flexible methylene bridge.

From a physicochemical perspective, the compound is moderately polar. The pyrimidinedione core contributes hydrogen bond donor and acceptor sites, while the nitrile group adds additional polarity. However, the aromatic systems introduce hydrophobic character, resulting in amphiphilic behavior.

Hydrogen bonding plays an important role in the compound’s properties. The carbonyl oxygens in the pyrimidinedione can act as hydrogen bond acceptors, while the ring nitrogens can participate in tautomeric forms and weak hydrogen bonding interactions. The nitrile group provides an additional acceptor site.

Chemically, the most reactive positions include the carbonyl groups of the pyrimidinedione and the C–Cl bond at the 6-position, which may undergo nucleophilic substitution under suitable conditions. The nitrile group is relatively stable but can participate in hydrolysis or reduction reactions under strong conditions.

The molecule’s structure resembles modified nucleobase derivatives, although the substitution pattern and benzonitrile linkage significantly alter its biological pairing behavior and electronic distribution compared with natural pyrimidines.

Overall, 2-[(6-chloro-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl)methyl]benzonitrile is a substituted pyrimidinedione derivative featuring a halogenated heterocyclic core linked via a methylene bridge to a nitrile-substituted aromatic ring. Its structure combines electron-deficient heterocycle chemistry with aromatic nitrile functionality, resulting in a moderately polar, chemically versatile organic compound.

References

2021. Synthesis of Alogliptin. Synfacts.
DOI: 10.1055/s-0040-1719789

2018. Palladium-Catalyzed Amination of Chloroheteroarenes with Secondary Amines. Synfacts.
DOI: 10.1055/s-0037-1609423

2011. Alogliptin. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-01-0200