I. Basic Product Information Table
Name: 4-Cyano-2-methoxybenzaldehyde
CAS No.: 21962-45-8
EINECS No.: 804-777-4
Chemical Formula: C₉H₇NO₂
Molecular Weight: 161.16
InChI InChI=1S/C9H7NO2/c1-12-9-4-7(5-10)2-3-8(9)6-11/h2-4,6H,1H3
Density 1.18 g/cm³ (1.2±0.1 g/cm³)
Boiling point 318.2°C at 760 mmHg
Flash point 138.3°C
Water solubility Slightly soluble in water; soluble in organic solvents such as ethanol, acetone, and dichloromethane
Vapor pressure 0.000368 mmHg at 25°C (0.003-2.3 Pa at 20-80°C)
Refractive index 1.54
Storage conditions Store in a sealed container under inert gas (nitrogen or argon) protection at 2-8°C
Sensitivity Sensitive to air
Appearance Grayish-white to pale yellow solid powder
Specific gravity 1.18
Color Grayish-white to pale yellow
MDL number MFCD07779491 Hazard Symbol Xi (Irritant)
Risk Terms R43 (May cause sensitization upon skin contact)
Safety Terms S36/37 (Wear appropriate protective clothing and gloves)
Customs Code 2926909090
II. Properties
4-Cyano-2-methoxybenzaldehyde is an aromatic compound containing three functional groups: an aldehyde group (-CHO), a methoxy group (-OCH₃), and a cyano group (-CN). This compound has a melting point of 109-111°C, a boiling point as high as 318.2°C (760 mmHg), a density of approximately 1.18 g/cm³, and a flash point of 138.3°C, classifying it as a high-boiling-point, low-volatility solid. Its vapor pressure is extremely low (approximately 0.000368 mmHg at 25°C), exhibiting good chemical stability, but it is sensitive to air and requires low-temperature storage under an inert gas atmosphere. This compound is slightly soluble in water but readily soluble in common organic solvents such as ethanol, acetone, dichloromethane, and ethyl acetate. Its PSA value is 50.09, and its LogP is approximately 1.25-1.42, indicating some lipophilicity. The presence of the aldehyde and cyano groups in its molecular structure endows it with strong reactivity, making it a key building block in various organic synthesis reactions.
III. Applications
4-Cyano-2-methoxybenzaldehyde is a key starting material and core intermediate in the synthesis of finerenone. Finerenone, developed by Bayer, is the world’s first nonsteroidal selective mineralocorticoid receptor antagonist (MRA), approved by the FDA in 2021 for the treatment of adult patients with chronic kidney disease (CKD) and type 2 diabetes. It significantly reduces the risk of persistently declining eGFR, end-stage renal disease, cardiovascular death, and hospitalization for heart failure.
Besides serving as a core intermediate in the synthesis of phenelzine, this compound is also widely used in:
Pharmaceutical intermediates: for the synthesis of various drug molecules containing dihydropyridine structures
Fine chemical synthesis: as a bifunctional aromatic building block containing cyano and aldehyde groups, participating in various organic transformations such as Knoevenagel condensation, reductive amination, and Grignard reactions
Pesticide intermediates: used in the construction of novel active pesticide molecules
Materials science: as a precursor for the synthesis of functional aromatic compounds
In the synthesis of phenelzine, 4-cyano-2-methoxybenzaldehyde typically undergoes a condensation reaction with acetoacetate compounds (such as tert-butyl acetoacetate, cyano acetoacetate, or diethyl malonate) to construct a dihydropyridine core structure, followed by ring closure, alkylation, hydrolysis, ammonolysis, and chiral resolution to obtain the final product.
IV. Preparation Methods Currently, the main industrial routes for synthesizing 4-cyano-2-methoxybenzaldehyde are as follows:
Route 1 (Mainstream Industrial Route): Starting with 3-methoxy-4-methylbenzoic acid, the following steps are followed:
The carboxyl acyl group is chlorinated and reacted with ammonia to generate 3-methoxy-4-methylbenzamide.
The amide is dehydrated in the presence of trifluoroacetic anhydride and N-methylmorpholine to generate 3-methoxy-4-methylbenzonitrile.
The methyl group is brominated with NBS to generate 4-dibromomethyl-3-methoxybenzonitrile.
Alkaline hydrolysis (e.g., using sodium iodide to promote hydrolysis) yields the target product, 4-cyano-2-methoxybenzaldehyde.
This route uses readily available raw materials, has clear steps, and is suitable for large-scale production.
Route 2 (Improved Route): Starting with 4-bromo-2-hydroxybenzaldehyde: Methylation occurs with dimethyl sulfate in the presence of potassium carbonate to generate 4-bromo-2-methoxybenzaldehyde. Cyanolysis is then performed using potassium hexacyanoferrate as the cyanide source under palladium acetate catalysis to obtain the target product.
This route has fewer steps but involves a precious metal catalyst and a toxic cyanide source, resulting in higher costs.
Route 3 (Other Routes): Starting with 4-methyl-3-methoxybenzoic acid, a continuous photo-free radical initiator-promoted methyl bromination reaction is used to selectively obtain a dibromo product (with monobromo byproducts controlled below 0.1%), followed by alkaline hydrolysis to an aldehyde. This route offers milder conditions and higher product purity.
V. Safety Information
GHS Hazard Category: Acute Oral Toxicity Category 4 (H302: Hazardous if swallowed)
Signal word: Warning
Pictogram: Exclamation mark (health hazard)
Main hazards: Harmful if swallowed; may cause sensitization upon skin contact; irritating to eyes, skin and respiratory tract
First aid measures:
Inhalation: Move to fresh air
Skin contact: Remove contaminated clothing and wash thoroughly with soap and water
Eye contact: Rinse with running water or saline solution and seek immediate medical attention
Ingestion: Rinse mouth, do not induce vomiting, seek immediate medical attention
Fire-fighting measures: Use dry powder, foam or carbon dioxide fire extinguishers; avoid using direct water streams
Spill handling: Collect spilled material in a closed container and absorb residue with an inert absorbent material
Handling precautions: In a well-ventilated area Handle in a cabinet; wear protective gloves, goggles, and a respirator; avoid inhaling dust; keep away from fire and heat sources.
Incompatible materials: strong oxidizers, strong acids, strong alkalis
Storage requirements: Store at 2-8°C in a sealed container under inert gas (nitrogen or argon) protection; keep away from oxidizers and acidic/alkaline substances.
Disposal: Dispose of according to local regulations; do not discharge into sewers or the natural environment.
Transportation information: Not a hazardous material (DOT/IATA), can be transported as general chemicals.
VI. Our Production Advantages and Capacity
As a professional pharmaceutical intermediate manufacturer, our company has the following core advantages in the production of 4-cyano-2-methoxybenzaldehyde:
Large-scale production capacity: Annual production capacity exceeds 10,000 kg, which can meet the bulk purchasing needs of large domestic and foreign pharmaceutical companies, supporting full-specification coverage from gram-level R&D samples to ton-level commercial supply.
High-purity products: Product purity ≥98% (HPLC), with custom specifications of ≥99% purity available; single impurities controlled below 0.1%, meeting the quality standards for API starting materials.
Strict quality control system: Equipped with a full range of analytical instruments including HPLC, GC, NMR, and MS; each batch provides a Certificate of Analysis (COA) and MSDS (Material Safety Data Sheet); third-party testing and verification supported.
Mature and stable process: Utilizes an optimized multi-step synthesis process with mild reaction conditions, high yield, and low waste emissions; key intermediates are controllable, ensuring a stable supply chain.
Cost competitiveness: Own production base, stable raw material procurement channels, and large-scale production significantly reduce unit costs, providing customers with competitive prices.
Customization services: Supports different packaging specifications (1kg/drum, 5kg/drum, 25kg/drum, etc.); custom products with special purity, crystal form, or particle size can be provided according to customer needs.
Compliance and certification: Production facilities meet GMP requirements and have a complete EHS management system; products can assist customers in completing the starting material audit required for API registration.
Fast Delivery: We maintain a large inventory, delivering to domestic customers within 3-5 business days and to international customers within 7-15 business days; we support various logistics methods including air and sea freight.
Technical Support: Our professional R&D team provides technical support services such as synthetic route consultation, impurity spectrum analysis, and analytical method development.
Post time: Jun-10-2026
