3-Chloro-2-hydroxy-5-methoxybenzaldehyde - ≥95% , CAS No.90110-33-1

CAS: 90110-33-1 Cat. No.: C998362 Formula: C₈H₇ClO₃ Peso molecolare: 186.590 Numero EC: 884-690-6

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifiche e purezza

≥95%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥95%

Nomi e identificatori

Sorrisi canonici

COC1=CC(=C(C(=C1)Cl)O)C=O

IUPAC Name

3-chloro-2-hydroxy-5-methoxybenzaldehyde

InChIKey

QBMCHZROYVXWMF-UHFFFAOYSA-N

INCHI

1S/C8H7ClO3/c1-12-6-2-5(4-10)8(11)7(9)3-6/h2-4,11H,1H3

Peso molecolare

186.590

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Phenols
      • Subclass Methoxyphenols

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Phenols
• Subclass: Methoxyphenols
• Intermediate Tree Nodes: Not available
• Direct Parent: Methoxyphenols
• Alternative Parents: Hydroxybenzaldehydes 4-alkoxyphenols Phenoxy compounds O-chlorophenols Methoxybenzenes Benzoyl derivatives Anisoles Chlorobenzenes Alkyl aryl ethers Aryl chlorides Vinylogous acids Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Methoxyphenol - 4-alkoxyphenol - Hydroxybenzaldehyde - Anisole - Benzaldehyde - Benzoyl - 2-halophenol - Phenoxy compound - 2-chlorophenol - Phenol ether - Methoxybenzene - Aryl-aldehyde - Halobenzene - Chlorobenzene - Alkyl aryl ether - Monocyclic benzene moiety - Aryl halide - Aryl chloride - Vinylogous acid - Ether - Organic oxide - Organooxygen compound - Aldehyde - Organohalogen compound - Organic oxygen compound - Organochloride - Hydrocarbon derivative - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as methoxyphenols. These are compounds containing a methoxy group attached to the benzene ring of a phenol moiety.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Proprietà chimiche e fisiche

• Peso molecolare: 186.590 g/mol
• XLogP3: 2.200
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 186.008 Da
• Monoisotopic Mass: 186.008 Da
• Topological Polar Surface Area: 46.500 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 162.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

Not applicable. No validated immunoassay or cell-based assay protocols are specified for this small-molecule building block. For synthetic use, see the Reaction Conditions section for representative literature procedures. Always adapt conditions to your specific substrate set and consult primary literature.

Biological Roles

• Item-specific note: This product is designated for research use only.

• General context (no clinical claims):

  • 2-Hydroxybenzaldehyde (salicylaldehyde) scaffolds and their imine derivatives are widely studied as ligands in bioinorganic chemistry; the O,N-bidentate chelation motif models enzyme active-site coordination.
  • Salicylaldimine–metal complexes can serve as spectroscopic probes for biomolecules and as catalysts for biomimetic oxidations (research context). The presence of an aryl chloride and methoxy substituent modulates electronic properties (Hammett parameters) and lipophilicity, which can influence binding to proteins and membranes in biochemical assays.
  • Phenolic functionality confers hydrogen-bonding donor ability; the aldehyde facilitates reversible covalent interactions (Schiff bases) with primary amines (e.g., lysine side chains) under certain conditions, a feature exploited in labeling and sensor development (laboratory research).

No endogenous biological role is associated with this synthetic aromatic aldehyde.

Buffer Applications

Not typically used as a buffering agent. As a hydrophobic aromatic aldehyde with a phenolic OH, it lacks the conjugate acid/base pair and pKa profile required for practical buffer systems in aqueous media. For laboratory workflows, refer instead to applications in synthetic chemistry, ligand formation, and condensations.

Green Alternatives

• Solvent choices (greener vs conventional) for typical reactions of salicylaldehydes (literature guidance):

| Application | Conventional solvent | Greener alternative | Notes | |---|---|---|---| | Imine (Schiff base) formation | Toluene, DCM | Ethanol, isopropanol, 2-MeTHF | Often feasible at reflux with azeotropic water removal or with molecular sieves. | | Knoevenagel condensation | DMF, DMSO | Water/ethanol blends, glycerol, PEG-400, MeCN | Organobase catalysis in EtOH/H2O frequently effective; avoids high-boiling dipolar aprotics. | | Cross-coupling (aryl chloride) | Dioxane/DMF | 2-MeTHF, CPME, propylene carbonate | Requires catalyst/ligand re-optimization; greener workup and lower peroxide risk vs ethers like THF. | | Oxidative cyclization to benzoxazoles | CH3CN/DCM | EtOAc, ethanol | Use air or H2O2 as terminal oxidant when compatible. |

• Operational improvements:
  • Replace inorganic bases (NaH, strong hydroxide) with weaker organic bases or solid-supported bases where compatible.
  • Employ flow or microwave heating to reduce reaction time/energy.
  • Prefer catalytic over stoichiometric halogen–metal exchange; use modern Pd/Ni catalysts active for aryl chlorides to avoid pre-activation.

Trade-offs: Greener solvents may reduce substrate solubility or alter selectivity; confirm with small-scale screening.

Pharmaceutical Uses

• Item-specific: No pharmacopeial grade or excipient designation is provided for this item; refer to CoA/Spec Sheet.

• General context (no therapeutic claims):

  • Such functionalized salicylaldehydes are commonly employed as synthetic intermediates in medicinal chemistry programs, enabling rapid access to salicylaldimines, benzoxazoles, benzofurans, chromenes, and elaborated anisoles via cross-coupling at the aryl chloride.
  • The aldehyde can be protected (acetal) to permit downstream manipulations (e.g., Suzuki or Buchwald–Hartwig couplings) toward API candidate scaffolds. Phenolic protection/deprotection strategies (MOM, Bn, SEM, TBS) provide orthogonality in multistep sequences.
  • No established role as an excipient is expected for this class; usage is typically confined to route scouting and library synthesis in R&D.

Physical Properties

• Item-specific (Product Data):

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Storage conditions: Room temperature (per Product Data).
  • Other specifications (bp, mp, density, solubility, UV cutoff, water/peroxide/metal limits): Not specified for this item; refer to CoA/Spec Sheet.

• Literature/expected properties for this class (reference only; not specifications):

  • Physical state: Many substituted salicylaldehydes are crystalline solids at ambient conditions due to intramolecular H-bonding (O–H···O=CH) that promotes lattice stabilization.
  • Polarity/solubility: Sparingly soluble in water; readily soluble in common organic solvents such as ethanol, methanol, acetone, acetonitrile, ethyl acetate, DMSO, DMF, dichloromethane, and THF. Phenolic OH enhances hydrogen-bonding; methoxy increases organic solubility.
  • Acidity/basicity: Phenolic pKa for salicylaldehydes typically ~8–10 (literature, depends on ring substituents); aldehyde carbonyl is not basic and has no pKa in water. Intramolecular H-bonding between 2-OH and the aldehyde oxygen is characteristic.
  • Partitioning: Aromatic aldehydes with phenolic/methoxy substituents generally display moderate hydrophobicity (positive logP) balanced by H-bonding capacity (literature trends).

Note: For any numeric values required in regulated workflows, consult the specific CoA/SDS for this lot.

Quality and Grades

• Item-specific (Product Data):

  • Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
  • Stabilizers/inhibitors: Not specified for this item; refer to CoA/Spec Sheet.

• Guidance on interpreting grades (general):

  • Research/technical grade aromatic building blocks are typically suitable for organic synthesis, screening, and materials R&D. If labeled “HPLC” or “LC-MS” grade, that would imply stringent control of UV-absorbing impurities and residual solvents for analytical applications; absent such notation, assume standard research grade.
  • If a stabilizer is present (not indicated here), it would generally be to suppress oxidation of the aldehyde to the corresponding acid; confirm by CoA.
  • For moisture/air-sensitive workflows (e.g., formation of metal complexes with salicylaldimines), consider purifying by recrystallization or column chromatography and drying under vacuum to remove adventitious water.

• Release documentation:

  • For exact assay, residual solvent profiles, and elemental analysis/HRMS reference, consult the lot-specific CoA/Spec Sheet, which supersedes any general statements.

Reaction and Applications

As an o-hydroxybenzaldehyde (salicylaldehyde) derivative bearing a meta-chloro and meta-methoxy substituent, this building block is versatile in coordination chemistry and heterocycle synthesis.

• Typical transformations (literature):

  • Schiff base formation: Condenses with primary amines/anilines to give salicylaldimines that can chelate metals (O,N-bidentate), enabling preparation of salen/salophen-type ligands and metal–organic frameworks.
  • Knoevenagel condensations: Reacts with active methylene compounds (e.g., malononitrile, cyanoacetates) under base catalysis to give o-hydroxycinnamaldehyde or arylidene products, often leading to cyclized chromenes/coumarans upon further treatment.
  • Intramolecular cyclizations: With o-aminophenols or o-phenylenediamines, forms benzoxazoles/benzimidazoles under oxidative conditions (Cu, I2/DMSO, PIDA, or aerobic catalysis).
  • Acetal/hemiacetal chemistry: Protect aldehyde as acetal for orthogonal manipulation of the aryl chloride or phenol.
  • Cross-coupling at C–Cl: After protecting the phenol if necessary (e.g., as methyl/benzyl ether or silyl ether), the aryl chloride can undergo Suzuki–Miyaura, Buchwald–Hartwig, or Sonogashira couplings (Pd/ligand systems optimized for aryl chlorides).
  • O-functionalization: Phenolic OH allows O-alkylation, O-acylation, carbonate/urethane formation; intramolecular H-bonding to the aldehyde can influence reactivity/stereochemical outcome in condensations.

• Use cases:

  • Precursor to ligand libraries (salicylaldimines) for catalysis and metal sensing.
  • Intermediate for halogen-retentive routes leading to densely substituted anisole/salicylate frameworks.

Practical tip: Drying the substrate (vacuum, mild heat) improves imine/Knoevenagel outcomes; trace water suppresses condensations and shifts equilibria.

Reaction Conditions

Literature-guidance examples for this class of substrates (reference only; not item specifications):

• Schiff base formation (salicylaldimines):

  • Solvent: EtOH, i-PrOH, or toluene; catalytic AcOH or p-toluenesulfonic acid if needed.
  • Conditions: 25–80 °C, 1–12 h; use 3 Å molecular sieves or Dean–Stark (in toluene) to remove water. Typical isolated yields: 70–95% with primary amines/anilines.

• Knoevenagel condensation (with malononitrile or ethyl cyanoacetate):

  • Base: Piperidine, ammonium acetate, or DBU (0.05–0.2 equiv).
  • Solvent: EtOH or EtOH/H2O (1:1); 25–60 °C, 0.5–4 h. Isolated yields often 80–95%.

• Benzoxazole formation (with o-aminophenol):

  • Catalyst/oxidant: Cu(OAc)2 with air or I2/DMSO; MeCN or EtOH as solvent.
  • Conditions: 60–110 °C, 4–16 h. Yields commonly 60–90% depending on substrate.

• Suzuki–Miyaura coupling at aryl chloride:

  • Catalyst: Pd2(dba)3 (1–2 mol%) with bulky biaryl phosphines (e.g., XPhos, SPhos 2–4 mol%).
  • Base: K3PO4 or Cs2CO3 (2–3 equiv). Solvent: 2-MeTHF, dioxane/H2O, or toluene/H2O. 80–110 °C, 6–18 h.
  • Protect phenol as needed to suppress competitive O-arylation.

• Aldehyde protection (acetalization):

  • Reagents: Ethylene glycol (3–5 equiv), catalytic p-TsOH; solvent: toluene or CH2Cl2 with molecular sieves.
  • Conditions: RT–reflux, 1–6 h; near-quantitative conversion commonly observed.

Note: Optimize for this substrate; substituents (OMe, OH, Cl) influence rates and selectivity.

Safety and Handling

• Item-specific (Product Data):

  • GHS classification, signal word, pictograms, H-statements: Not specified for this item; refer to SDS.
  • Storage conditions: Room temperature.

• General safety considerations for aromatic aldehydes/phenols (literature/typical guidance; defer to SDS):

  • Hazards: May cause skin and eye irritation; aldehydes can be sensitizers and irritants to mucous membranes. Phenolic OH may enhance corrosive/irritant effects compared with simple benzaldehydes.
  • PPE: Wear lab coat, safety glasses or goggles, and suitable chemical-resistant gloves (e.g., nitrile). Use in a chemical fume hood to avoid inhalation of vapors/aerosols.
  • Handling: Avoid prolonged exposure to air and strong bases/acids that could promote side reactions (oxidation to the corresponding acid, acetalization, or ether cleavage). Keep container tightly closed to minimize air/moisture ingress.
  • Incompatibilities: Strong oxidizers (risk of rapid oxidation), strong bases (phenolate formation; potential for side reactions), strong acids (may accelerate acetalization or demethylation under harsh conditions), and reducing agents (may reduce the aldehyde).
  • First aid (overview; consult SDS): If on skin/eyes, rinse cautiously with water for several minutes. If inhaled, move to fresh air. If ingested, rinse mouth; do not induce vomiting; seek medical attention.
  • Waste: Collect organic waste according to institutional hazardous waste procedures. Do not release to the environment.

Always consult the product-specific SDS for authoritative hazard classification and response.

Solvent Selection

This compound is a moderately polar, hydrogen-bonding-capable aromatic aldehyde (phenolic donor, ether acceptor) with low water solubility.

• Practical solvent choices (general expectations):

  • Protic: Methanol, ethanol, isopropanol typically dissolve well and are useful for imine (Schiff base) formation and condensations.
  • Aprotic polar: Acetonitrile, acetone, DMF, DMSO provide high solubility for coupling or cyclization chemistry; facilitate base-catalyzed Knoevenagel reactions.
  • Moderately polar aprotic: THF, 2-MeTHF, ethyl acetate, dioxane balance solubility and ease of removal.
  • Nonpolar chlorinated: Dichloromethane/chloroform often give excellent solubility for electrophilic aromatic transformations and acylations.

• Miscibility and selection tips:

  • Water: Generally poor solubility; biphasic or cosolvent systems (EtOH/H2O, MeCN/H2O) are common when using aqueous bases or catalysts.
  • For air/moisture-sensitive steps (e.g., metal complexation of salicylaldimines), use anhydrous solvents and inert atmosphere.
  • For green chemistry, consider 2-MeTHF or EtOAc over DCM/THF when compatible with reactivity.

• Quick comparison (general):

  • Ethanol: benign, supports imine formation; slower for poorly nucleophilic amines.
  • Acetonitrile: good for condensations/oxidations; easy workup.
  • DMSO/DMF: maximum solubility; more challenging removal; useful for high-temperature cyclizations.

Storage and Reconstitution

• Item-specific storage: Room temperature (per Product Data). Protect from moisture and prolonged air exposure to minimize slow oxidation of the aldehyde to the corresponding acid.

• Packaging/shipping: Shipped in standard chemical containment; specific shipping conditions not specified for this item; refer to CoA/Spec Sheet.

• Reconstitution and working solutions (general guidance):

  • Solubility: Readily dissolves in common organic solvents (EtOH, MeOH, acetone, acetonitrile, DMSO, DMF, CH2Cl2, THF). For stock solutions, dry solvent is recommended for water-sensitive condensations.
  • Stock preparation: Prepare concentrated stocks (e.g., 0.1–1.0 M) in dry MeCN, EtOH, or DMSO as required by the intended reaction. Store tightly capped under inert gas for extended periods.
  • Stability: Aldehydes can slowly oxidize; consider storing under nitrogen/argon and including a desiccant. Avoid strong light and heat.
  • Freeze–thaw: Not generally applicable unless storing solutions; minimize freeze–thaw by aliquoting solutions.

For long-term storage recommendations specific to the lot (including retest date), consult the CoA/Spec Sheet and SDS. Research use only.

Structure and Identity

A functionalized salicylaldehyde bearing chloro and methoxy substituents; useful as an electrophilic, orthogonally functionalized aromatic building block.

• Item-specific (Product Data):

  • Product name: 3-Chloro-2-hydroxy-5-methoxybenzaldehyde (SKU: C998362)
  • CAS: 90110-33-1
  • InChIKey: 292595 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular formula: Not specified in Product Data. See computed/literature below.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

• Computed/literature identity (non-specification; for reference):

  • Empirical formula (derived from name): C8H7ClO3
  • Formula mass (calculated): ~186.59 g/mol
  • Core structural features: benzaldehyde ring (–CHO) with ortho phenolic –OH (2-position), chloro at 3-position, and methoxy at 5-position; one aldehydic proton; three oxygen atoms (phenol, methoxy ether, carbonyl); one aryl chloride.
  • 2D description: A 1,2,3,5-tetrasubstituted benzene. Starting from the aldehyde carbon (position 1), clockwise: 2-OH (ortho), 3-Cl (meta), 4-H, 5-OMe (meta), 6-H, returning to 1-CHO.

• Stereochemistry: None (achiral small molecule).

Synthetic Utility

• Orthogonal handles (functional groups):

  • Aldehyde (–CHO): Electrophilic; engages in imine formation, Wittig/HWE olefinations, cyanohydrin formation, and reductive aminations (via imine intermediates).
  • Phenol (–OH): Nucleophilic after deprotonation; O-alkylation/acylation; can direct ortho-metalation (DoM) of adjacent positions when protected; engages in intramolecular H-bonding that can bias conformations.
  • Aryl chloride (–Cl): Cross-coupling handle (Suzuki, Buchwald–Hartwig, Sonogashira) with Pd/Ni catalysts; also enables nucleophilic aromatic substitution in suitably activated contexts (here, activation is limited by ring substitution but can proceed under strong conditions).
  • Methoxy (–OMe): Electron-donating; modulates ring electronics; can be demethylated (e.g., BBr3) to catechol-like patterns if required.

• Retrosynthetic value:

  • Serves as a convergent node: aldehyde allows late-stage diversification (condensations/olefinations) while the aryl chloride enables parallel diversification via C–C/C–N/C–O couplings.
  • Salicylaldimine derivatives are gateways to metal complexes and subsequent oxidative or cycloaddition chemistry.

• Protection strategies:

  • Aldehyde: cyclic/acetonide acetals (ethylene glycol, trimethyl orthoformate) under acid catalysis.
  • Phenol: benzyl, silyl (TBS/TBDPS), or carbonate protections; selection guided by intended coupling/oxidation conditions.

Target Specificity

Not applicable. This product is a small-molecule aromatic aldehyde, not an antibody, protein, or nucleic-acid reagent. No antigen/epitope, species reactivity, clone, or isotype information applies.