4-Chloro-2,3-dihydropyridazin-3-one: Properties & Applications
4-Chloro-2,3-dihydropyridazin-3-one: Properties & Applications
4-chloro-2,3-dihydropyridazin-3-one is a chlorinated dihydropyridazinone heterocycle widely employed as a versatile synthetic building block in medicinal chemistry and the preparation of biologically active pyridazinone derivatives.
- IUPAC Name
- 4-chloro-2,3-dihydropyridazin-3-one
- Molecular Formula
- C4H3ClN2O
- Molecular Weight
- 130.53 g/mol
- Core Scaffold
- Six-membered dihydropyridazinone ring with C4 chloro substituent
- Key Functional Groups
- Vinyl chloride (C4–Cl), lactam carbonyl (C3=O), NH
- Primary Research Use
- Electrophilic building block for nucleophilic aromatic substitution and cross-coupling reactions
- Aladdin SKU
- C174888
Chemical Structure and Key Physicochemical Properties
4-Chloro-2,3-dihydropyridazin-3-one (CAS registry; molecular formula C4H3ClN2O; MW 130.53 g/mol) belongs to the pyridazinone family of nitrogen-containing six-membered heterocycles. The ring system comprises two adjacent nitrogen atoms at positions 1 and 2, a lactam carbonyl at C3, and a chlorine substituent at C4, which activates the adjacent carbon toward nucleophilic displacement.
The partial saturation at the N2–C3 bond confers a dihydro character, distinguishing it from fully aromatic pyridazin-3(2H)-ones. This partial unsaturation lowers the ring aromaticity while retaining the electrophilic character at C4, making the compound a particularly reactive scaffold for downstream functionalization. The NH group at N2 provides an additional handle for N-alkylation or N-acylation reactions under mild basic conditions.
Physical properties such as exact melting point, solubility, and logP should be confirmed from the current certificate of analysis (CoA) supplied with Aladdin product C174888, as batch-specific data may vary.
Synthesis Utility and Reaction Chemistry
The C4 chloro substituent in 4-chloro-2,3-dihydropyridazin-3-one acts as an excellent leaving group under nucleophilic aromatic substitution (SNAr) conditions. The electron-withdrawing lactam carbonyl at C3 and the ring nitrogen atoms combine to sufficiently activate C4 toward attack by oxygen, nitrogen, sulfur, and carbon nucleophiles, enabling library synthesis of 4-substituted pyridazin-3(2H)-one derivatives.
In addition to SNAr chemistry, the vinyl chloride character at C4 makes this building block compatible with palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura, Negishi, and Buchwald–Hartwig protocols, allowing introduction of aryl, heteroaryl, alkyl, and amino groups with high selectivity. The NH functionality can be protected or elaborated prior to cross-coupling when orthogonal functionalization is required.
Common synthetic sequences employing this intermediate include: (1) selective N-alkylation followed by C4-SNAr to install diverse heteroatom substituents; (2) Pd-catalyzed C–C bond formation at C4 to access biaryl pyridazinone pharmacophores; and (3) sequential dual functionalization exploiting both the C4 chlorine and the N–H position to generate structurally complex heterocyclic arrays.
Applications in Medicinal Chemistry and Drug Discovery
The pyridazin-3(2H)-one scaffold is well-represented in bioactive compounds and approved pharmaceuticals, making 4-chloro-2,3-dihydropyridazin-3-one a strategically important intermediate for drug discovery programs. Pyridazinone-containing compounds have been reported to exhibit a range of biological activities, including phosphodiesterase (PDE) inhibition, kinase modulation, antimicrobial activity, and anti-inflammatory effects, underscoring the pharmacological relevance of this heterocyclic core.
By leveraging the reactivity at C4, medicinal chemists can rapidly diversify the pyridazinone core to generate focused libraries for structure–activity relationship (SAR) studies. The compact, planar ring system facilitates favorable interactions with biological targets through hydrogen-bond donation (N–H), hydrogen-bond acceptance (C=O, ring N), and hydrophobic stacking, providing a multi-point pharmacophore in a low-molecular-weight scaffold.
Researchers engaged in fragment-based drug design (FBDD) may find this compound particularly valuable as a fragment hit or fragment linker, given its low molecular weight (130.53 g/mol) and the ease with which structural elaboration can be performed at two distinct sites.
Handling, Storage, and Laboratory Safety Guidelines
As with all reactive heterocyclic intermediates, standard laboratory safety practices must be followed when working with 4-chloro-2,3-dihydropyridazin-3-one. Researchers should consult the Safety Data Sheet (SDS) provided by Aladdin Scientific (product C174888) before use. Personal protective equipment (PPE) including chemical-resistant gloves, safety goggles, and a laboratory coat is recommended. Handling should be performed in a well-ventilated fume hood to minimise inhalation exposure.
For storage, the compound should be kept in a tightly sealed container away from moisture, heat, and incompatible materials such as strong oxidisers and bases. Cool, dry storage conditions (typically 2–8 °C or as specified on the CoA) are advised to preserve reagent integrity over time. The specific hazard classification, GHS pictograms, and first-aid measures are detailed in the product SDS; always refer to the most current version available on the Aladdin Scientific website.
Waste disposal must comply with applicable local, national, and institutional regulations for chlorinated organic compounds. Do not pour down the drain; collect in appropriate labelled waste containers for disposal by a licensed chemical waste contractor.
Frequently asked questions
What types of nucleophiles can displace the chlorine at C4 of 4-chloro-2,3-dihydropyridazin-3-one?
The electron-deficient C4 position undergoes nucleophilic aromatic substitution (SNAr) with a broad range of nucleophiles, including primary and secondary amines (N-nucleophiles), alkoxides and phenols (O-nucleophiles), and thiolates (S-nucleophiles). Carbon nucleophiles may also be employed under appropriate activating conditions or via palladium-catalyzed cross-coupling. Reaction conditions (solvent, base, temperature) should be optimized for each nucleophile class.
Is 4-chloro-2,3-dihydropyridazin-3-one suitable for fragment-based drug discovery?
Yes. With a molecular weight of approximately 130.53 g/mol, the compound falls well within the typical fragment molecular weight range (≤300 g/mol). Its two distinct reactive sites (C4-Cl and N–H) allow rapid structural elaboration in multiple directions, making it an attractive fragment hit or linker for fragment-based drug design (FBDD) campaigns targeting a variety of biological receptors and enzymes.
How should 4-chloro-2,3-dihydropyridazin-3-one (C174888) be stored to maintain stability?
The compound should be stored in a tightly sealed container under cool, dry conditions, typically at 2–8 °C or as specified on the certificate of analysis (CoA) accompanying Aladdin product C174888. Protect from moisture, light, and incompatible reagents such as strong oxidisers and bases. Always refer to the most current SDS and CoA for batch-specific storage guidance.
Can the NH group of 4-chloro-2,3-dihydropyridazin-3-one be selectively functionalized independently of the C4 chloro group?
Yes, selective N-functionalization is achievable. Under mild basic conditions, the N–H can be alkylated using alkyl halides or arylated via Ullmann-type or Buchwald–Hartwig coupling, provided reaction parameters are carefully controlled to avoid concurrent SNAr at C4. Sequential protection–deprotection strategies may also be employed when orthogonal reactivity at both positions is desired.
References
- Aladdin Scientific product page and certificate of analysis for 4-chloro-2,3-dihydropyridazin-3-one, SKU C174888.
- General reference on pyridazinone pharmacology and synthetic utility — textbook-level knowledge; specific literature citations to be confirmed by subject-matter expert.
- General reference on nucleophilic aromatic substitution (SNAr) reactions of chloroheterocycles — standard organic chemistry knowledge; specific literature citations to be confirmed.
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