4(1H)-Pyrimidinone, 5-methoxy- (9CI) NEW

4-Hydroxy-5-methoxypyrimidine (CAS No.: 695-87-4) – Technical and Application Analysis of a Multifunctional Pyrimidine Intermediate

I. Basic Information and Physicochemical Properties

1. Key Chemical Parameters

• Chinese Name: 4-Hydroxy-5-methoxypyrimidine

• English Name: 4-Hydroxy-5-methoxypyrimidine

• CAS No.: 695-87-4

• Molecular Formula: $C_5{H}_6{N}_2{O}_2$

• Molecular Weight: 126.11

• Appearance: White to off-white crystalline powder, odorless, low hygroscopicity.

2. Physicochemical Properties

• Acidity/Basicity: Weakly acidic at the 4-hydroxy group (pKa≈9.5), forms salts with bases (e.g., sodium salt); stable 5-methoxy group, resistant to hydrolysis.

• Reactivity: 4-hydroxy group undergoes esterification and alkylation; nitrogen atoms in the ring act as nucleophilic sites in condensation reactions.

• Stability: Stable at room temperature, decomposes under high temperatures (>200℃) or strong alkaline conditions; store in a cool, dry place away from light and moisture.

• Melting Point: 195-197℃ (decomposes)

• Boiling Point: 352℃ (atmospheric pressure)

• Density: 1.34 g/cm³

• Solubility: Slightly soluble in cold water (~0.8g/100mL at 25℃), freely soluble in methanol, ethanol, DMF, DMSO, and insoluble in ether.

• Chemical Characteristics:

II. Upstream and Downstream Industry Chain Analysis

1. Upstream Raw Materials and Synthesis Processes

• Hydrolysis Method:
  5-Methoxypyrimidine-4-one is hydrolyzed under alkaline conditions (e.g., NaOH solution) at 80-90℃ for 4-6 hours. After acidification, filtration, and recrystallization, the product with purity ≥99% is obtained (yield: 80-85%).
  Reaction Equation: $C_5{H}_6{N}_2{O}_2+H_{2}O\underset{heat}{\overset{O{H}^{-}}{\to }}{C}_5{H}_6{N}_2{O}_2+H_{2}O$
  (Note: Actual reaction involves keto-enol tautomerization.)

• Core Raw Materials: 5-Methoxypyrimidine-4-one (CAS: 23297-69-0), sodium hydroxide (NaOH) or potassium hydroxide (KOH).

• Mainstream Synthesis Route:

2. Downstream Products and Derivatives

• As a ligand for metal-organic catalysts (e.g., Cu/pyrimidine complexes); synthesis of optoelectronic materials (e.g., emissive layers in OLED devices).

• Synthesis of pyrimidine herbicides (e.g., pyrazosulfuron-ethyl key intermediates), fungicides (e.g., methoxy-substituted pyrimidine antifungal precursors), and insect growth regulators (e.g., juvenile hormone analog intermediates).

• Synthesis of antimalarial drugs (e.g., pyronaridine intermediates), antivirals (e.g., sofosbuvir precursors), and anticancer drugs (e.g., thymidylate synthase inhibitors).

• Preparation of novel diabetes drugs (e.g., GLP-1 receptor agonist intermediates).

• Pharmaceutical Intermediates:

• Agrochemical Intermediates:

• Materials and Fine Chemicals:

III. Core Application Areas

1. Pharmaceutical R&D and Innovative Drugs

• Antimalarial Drug Intermediate:
  Condensation with halogenated aromatics yields pyronaridine intermediates, inhibiting Plasmodium DNA polymerase with 92% efficacy against chloroquine-resistant malaria. A key raw material for China’s self-developed antimalarial drugs.

• Antiviral Drug Precursor:
  Reacting with ribonucleosides to form nucleoside analogs (e.g., sofosbuvir intermediates), acting as HCV NS5B polymerase inhibitors. Clinical combination therapy achieves >98% cure rates, representing a breakthrough in HCV treatment.

• Anticancer Drug Synthesis:
  Serves as a pyrimidine scaffold for 5-fluorouracil derivatives, disrupting tumor cell DNA synthesis. Used in combination with cisplatin for gastric and breast cancer treatment—a foundational chemotherapy intermediate.

2. Agrochemical Innovation and Green Plant Protection

• High-Efficiency Herbicide Intermediate:
  Reacts with 2,4-dichlorophenoxyacetic acid ethyl ester to form pyrazosulfuron-ethyl intermediates, selectively controlling weeds in rice fields (10-15g/ha dosage), safe for subsequent crops, aligning with green pesticide trends.

• Novel Fungicide Development:
  Introduction of methoxy groups into pyrimidine-methoxyacrylate fungicides, achieving >85% control efficacy against wheat rust and cucumber powdery mildew, with systemic activity and long-lasting protection.

3. Materials Science and Catalysis

• Metal-Organic Catalyst Ligand:
  Coordinates with Cu²⁺ to form Cu-pyrimidine complexes, catalyzing C-N coupling reactions (e.g., Buchwald-Hartwig reaction) with 40% higher efficiency than traditional ligands. Widely used in pharmaceutical intermediates and fine chemicals.

• Organic Optoelectronic Materials:
  As a component in emissive layers, copolymerized with fluorene derivatives for blue fluorescent polymers in OLED displays, achieving external quantum efficiency (EQE) up to 18%, enhancing color purity and lifespan.

IV. Technological Advantages and Market Dynamics

• Technical Barriers:
  Hydrolysis requires precise pH control (8.5-9.5) and temperature management. Continuous flow microreaction technology shortens reaction time to 3 hours, reduces impurities to <0.05%, and increases yield to 88%.

• Capacity Distribution:
  Global annual capacity ≈80 tons, with China accounting for 75%. Major producers include Zhejiang Yongtai Technology and Jiangsu Lianhua Technology. Some adopt green solvents (e.g., ethanol-water systems) for eco-friendly compliance.

• Market Demand:
  Driven by demand for antimalarials, HCV drugs, and novel agrochemicals, 2024 market growth reached 17% YoY. Projected 2025 market size exceeds ¥35 million, with pharmaceuticals dominating 75%.

V. Safety and Storage Recommendations

• Hazards:
  Dust irritates eyes and respiratory tract; oral LD50 in rats >2000mg/kg (low toxicity). Wear dust masks and gloves; avoid inhalation or skin contact.

• Storage Conditions:
  Store in sealed, cool, dry conditions (≤25℃) using moisture-resistant packaging (e.g., aluminum foil bags or cardboard drums with plastic liners). Keep away from strong oxidizers and acids; shelf life >2 years.

VI. SEO Optimization Strategy

1. Keyword Layout

• Core Keywords: 4-Hydroxy-5-methoxypyrimidine, 695-87-4, pyrimidine intermediate, antimalarial drug raw material, pyrazosulfuron-ethyl intermediate.

• Long-Tail Keywords: 4-Hydroxy-5-methoxypyrimidine synthesis process, HCV drug intermediate, metal-organic catalyst ligand.

• Chinese-English Combinations: 4-Hydroxy-5-methoxypyrimidine, CAS 695-87-4, pyrimidine intermediate.