4-Chloro-5-methoxy-2-methylpyrimidine (CAS No.: 698-33-9) – Technical and Market Analysis of a Highly Active Pyrimidine Intermediate

I. Basic Information and Physicochemical Properties

1. Key Chemical Parameters

• Chinese Name: 4-Chloro-5-methoxy-2-methylpyrimidine

• English Name: 4-Chloro-5-methoxy-2-methylpyrimidine

• CAS No. 698-33-9

• Molecular Formula: $C_6{H}_{7}Cl{N}_{2}O$

• Molecular Weight: 160.58

• Appearance: White to off-white crystalline powder, odorless, stable in air.

2. Physicochemical Properties

• Reactivity: The chloro group at the 4-position undergoes nucleophilic substitution (e.g., replaced by amino, hydroxyl, thiol groups), serving as a key site for pyrimidine derivative synthesis.

• Stability: The methoxy (-OCH?) and methyl (-CH?) groups enhance ring stability and adjust molecular polarity. Stable at room temperature but prone to hydrolysis under strong alkaline conditions. Avoid contact with strong oxidants/bases.

• Freely soluble in methanol, ethanol, acetonitrile, DMF, etc.

• Slightly soluble in water (≈0.5 g/100 mL at 25°C).

• Insoluble in petroleum ether.

• Melting Point: 68-70°C

• Boiling Point: 265-267°C (atmospheric pressure)

• Density: 1.26 g/cm3

• Solubility:

• Chemical Characteristics:

II. Upstream and Downstream Industry Chain Analysis

1. Upstream Raw Materials and Synthesis Process

• React 2-methyl-4,5-dihydroxypyrimidine with POCl? in DMF under reflux for 4-chlorination, yielding 4,5-dichloro-2-methylpyrimidine.

• React with sodium methoxide in methanol at 60-80°C to introduce the 5-methoxy group. Purify via vacuum distillation and recrystallization (ethanol/water system) to achieve ≥99% purity. Overall yield: 65-70%.

• Reaction Equations:
  $C_6{H}_8{N}_2{O}_2+POC{l}_3\to C_6{H}_{6}C{l}_2{N}_2+\dots$
  $C_6{H}_{6}C{l}_2{N}_2+C{H}_{3}ONa\to C_6{H}_{7}Cl{N}_{2}O+NaCl$

• 2-Methyl-4,5-dihydroxypyrimidine (CAS: 5756-58-1)

• Phosphoryl chloride (POCl?)/methanol

• Core Raw Materials:

• Main Synthesis Route:
  Chlorination-methoxylation method:

2. Downstream Products and Derivatives

• Metal-organic catalyst ligands (e.g., Pd/pyrimidine complexes).

• Organic optoelectronic materials (e.g., OLED emissive layer components).

• Antivirals (e.g., influenza neuraminidase inhibitors).

• Anticancer drugs (e.g., PI3K kinase inhibitor precursors).

• Diabetes treatments (e.g., GLP-1 receptor agonist intermediates).

• Herbicides (e.g., intermediates for pyrazosulfuron-ethyl, bispyribac-sodium).

• Fungicides (e.g., precursors for methoxy-pyrimidine antifungals).

• Insect growth regulators (e.g., juvenile hormone analogs).

• Agrochemical Intermediates:

• Pharmaceutical Intermediates:

• Materials Science:

III. Core Application Fields

1. Agrochemical Innovation and Green Plant Protection

• High-Efficiency Herbicide Intermediate:
  Condensation with 2,4-dichlorophenoxyacetic acid ethyl ester yields a key intermediate for pyrazosulfuron-ethyl, selectively controlling annual grasses and broadleaf weeds in rice fields (10-15 g/ha dosage). Safe for subsequent crops, aligning with low-residue pesticide trends.

• Novel Fungicide Development:
  Methoxy-pyrimidine acrylate fungicides with >90% efficacy against wheat powdery mildew and grape downy mildew. Offers protective and curative effects with a 14-day duration, reducing application frequency.

2. Pharmaceutical R&D and Innovative Drugs

• Antiviral Drug Precursors:
  Reacts with nucleoside analogs to produce influenza inhibitors (e.g., oseltamivir analogs) targeting H1N1, H3N2 via neuraminidase inhibition.

• Anticancer Drug Synthesis:
  Serves as a pyrimidine scaffold for PI3K/mTOR dual inhibitors, blocking tumor proliferation signals and angiogenesis. Effective in ovarian and kidney cancers, with strong clinical synergy.

3. Materials Science and Catalysis

• Metal-Organic Catalyst Ligands:
  Pd-pyrimidine complexes enhance Suzuki-Miyaura coupling efficiency by 30%, widely used in pharmaceuticals and fine chemicals, especially fluorinated heterocycles.

• Organic Optoelectronics:
  Copolymerized with fluorene derivatives for yellow fluorescent OLED polymers, achieving 15% external quantum efficiency (EQE) and improving color saturation/stability.

IV. Technical Advantages and Market Dynamics

• Technical Barriers:

• Chlorination requires precise POCl? dosing and temperature control to avoid over-chlorination.

• Microwave-assisted synthesis shortens methoxylation to 4 hours, boosting yields to 75% with <0.1% impurities.

• Capacity Distribution:

• Global capacity ≈30 tons/year, 70% in China (Jiangsu Zhongqi, Zhejiang Yongtai). Main process: chlorination-methoxylation. Some adopt green solvents (e.g., ionic liquids) to replace DMF.

• Market Demand:

• Driven by agrochemical/pharmaceutical R&D, 2024 demand surged 22% YoY. 2025 market projected to exceed $1.5M, with agrochemicals (60%) and pharmaceuticals (30%) leading.

V. Safety and Storage Recommendations

• Hazards:

• Dust irritates eyes/respiratory tract. LD50 (rat oral) >2000 mg/kg (low toxicity). Wear dust masks/nitrile gloves; avoid inhalation/skin contact.

• Storage:

• Seal in cool, dry conditions (≤25°C), using moisture-proof packaging (aluminum foil bags/lined cardboard drums). Avoid oxidants, bases, and humidity. Shelf life: 2 years.

VI. SEO Optimization Strategy

1. Keyword Layout

• Core Keywords:
  4-Chloro-5-methoxy-2-methylpyrimidine, 698-33-9, pyrimidine intermediate, pyrazosulfuron precursor, antiviral drug intermediate.

• Long-tail Keywords:
  4-Chloro-5-methoxy-2-methylpyrimidine synthesis process, agrochemical intermediate pricing, metal-organic catalyst ligand.

• Chinese-English Combinations:
  4-Chloro-5-methoxy-2-methylpyrimidine, CAS 698-33-9, pyrimidine intermediate.

Translation formatted to maintain technical precision, structural clarity, and SEO-friendly keyword integration.