This compound belongs to the class of organic compounds known as phenylmorpholines. These are aromatic compounds containing a morpholine ring and a benzene ring linked to each other through a CC or a CN bond.
External Descriptors
Not available
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.
Certificati (CoA, COO, BSE/TSE e tabella di analisi)
C of A & Other Certificates(BSE/TSE, COO):
Analytical Chart:
Proprietà chimiche e fisiche
Peso molecolare
241.670 g/mol
XLogP3
1.800
Hydrogen Bond Donor Count
1
Hydrogen Bond Acceptor Count
4
Rotatable Bond Count
2
Exact Mass
241.051 Da
Monoisotopic Mass
241.051 Da
Topological Polar Surface Area
49.800 Ų
Heavy Atom Count
16
Formal Charge
0
Complexity
256.000
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
Calcolatori di soluzioni
Molarity Calculator
Determine the necessary mass, volume, or concentration for preparing a solution.
Dilution Calculator
Determine the dilution needed to prepare a stock solution.
Reconstitution Calculator
Recensioni
Recensioni dei clienti
Application Protocols
There are no item-specific validated biological assay protocols (e.g., WB, IHC, IF, FC) for this small-molecule reagent.
Practical lab usage guidance (general)
Stock solution preparation for screening: Dissolve in DMSO (e.g., 10–50 mM), sonicate if needed; filter (0.22 µm PTFE) for sterile applications. Dilute into assay buffer maintaining final DMSO ≤1–2% v/v to minimize solvent effects.
Synthetic setup: For amide couplings, dry solvents and bases; consider in situ base (DIPEA) and stoichiometry control. For cross-couplings, pre-dry substrate or convert to an ester to avoid acid–base interactions with catalytic system.
Note: The above are general good-practice pointers, not tested protocols for this specific product.
Biological Roles
Item-specific biological/biochemical roles: Not specified for this item; this product is supplied for research use only.
Literature/general context (no medical claims)
Structural class: Aromatic carboxylic acid bearing a tertiary amino ether (morpholine). Such motifs are frequently used as fragments or pharmacophores in medicinal chemistry due to the balance of polarity (morpholine) and aromaticity (benzoic acid core).
Ionization behavior: The co-existence of a weak base (morpholine N) and a weak acid (benzoic acid) affords pH-dependent ionization states (zwitterionic, cationic, anionic), influencing membrane permeability and aqueous solubility. This is useful for ADME optimization studies and for tuning chromatographic retention in analytical methods.
Protein interaction potential: Carboxylates can engage in salt bridges and H-bonds with basic residues; morpholine oxygen and nitrogen are H-bond acceptors. These features are often exploited in ligand–protein binding design during SAR exploration.
Metabolic considerations (general): Aromatic acids may undergo conjugation (e.g., glucuronidation) and the morpholine ring may be susceptible to N-oxidation or ring-opening under metabolic conditions (literature). These are generalizable features of the motif, not claims about this specific compound’s in vivo fate.
Reminder: This product is intended strictly for laboratory research and development; no clinical, diagnostic, or therapeutic use is implied.
Buffer Applications
This compound is not used as a classical buffering agent. While it contains an acidic carboxyl group and a basic morpholine nitrogen, it is not part of standard biochemical buffer systems.
Practical note
For aqueous workups or analytical methods, pH can modulate solubility: deprotonate (pH > 7) to increase solubility as the carboxylate; protonate (pH < 5) to increase solubility via the morpholinium salt. However, these are solubility strategies, not buffering applications.
For buffering needs, choose established systems (e.g., phosphate, acetate, Tris, HEPES) with well-characterized pKa/pH ranges.
No item-specific buffer recipes or pH ranges are provided for this product.
Green Alternatives
Opportunities to improve the sustainability profile when working with 3-chloro-4-morpholinobenzoic acid largely involve solvent and coupling-reagent choices.
Greener solvent swaps (literature guidance)
Replace DMF/DMAc/NMP with Cyrene, GVL, or propylene carbonate for amidations when compatible with reagents.
Use 2-MeTHF or CPME instead of THF/Et2O; these offer better safety (lower peroxide tendency than ethers like THF) and improved lifecycle metrics.
Favor EtOAc or alcohols (MeOH/EtOH) for extractions and recrystallizations over chlorinated solvents.
Coupling reagent considerations
DMTMM in green solvents can substitute for HATU/HBTU (minimizing PF6− waste).
CDI-mediated couplings generate CO2/imidazole as benign byproducts (ensure amine compatibility).
Enzymatic esterifications in green solvents (e.g., 2-MeTHF, supercritical CO2) may be viable for certain transformations.
Process-intensification options
Microwaves or flow chemistry to shorten reaction times and reduce solvent volumes.
Aqueous micellar catalysis (e.g., TPGS-750-M) for Suzuki couplings of aryl chlorides can cut organic solvent usage (verify substrate compatibility with amphiphiles).
Comparison snapshot (general)
Traditional: DMF/DCM, HATU/DIPEA, Pd(PPh3)4 in dioxane.
Greener: Cyrene/EtOAc, DMTMM or CDI, Pd with tailored ligands in water/micelles or 2-MeTHF.
Note: Evaluate green alternatives with small-scale pilots; substrate-specific solubility and catalyst tolerance determine feasibility.
Pharmaceutical Uses
Item-specific pharmacopeial status or excipient role: Not specified for this item; refer to CoA/Spec Sheet.
General formulation/manufacturing context (no therapeutic claims)
Role in discovery chemistry: 3-chloro-4-morpholinobenzoic acid serves as a versatile intermediate for synthesizing amide, ester, or heterocycle derivatives during lead optimization. The para-morpholine enhances aqueous compatibility, while the carboxylate enables straightforward conjugation to amines.
Salt-formation strategy: The carboxylic acid can form salts with organic bases (e.g., tromethamine) for processability; alternatively, the morpholine nitrogen can be protonated to form acid addition salts, aiding crystallization or purification of intermediates.
Analytical considerations: Dual ionizable centers facilitate LC–MS detection under both positive and negative ESI, beneficial in bioanalytical method development for derived compounds.
Impurity profiling: Monitor for hydrolysis of activated acid derivatives and for dehalogenated aromatics after cross-coupling steps; these considerations pertain to synthetic derivatives rather than this catalog item itself.
Note: This product is supplied strictly for research and development; it is not approved as an active ingredient or excipient.
Physical Properties
Item-specific data from Product Data
Appearance: Not specified for this item; refer to CoA/Spec Sheet.
Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
Literature/computed values (for reference; not item specifications)
Molecular formula (literature): C11H12ClNO3
Molecular weight (calculated): ~241.67 g/mol
Acid–base properties: The molecule contains a carboxylic acid (acidic) and a tertiary amine (basic) in the morpholine ring.
pKa (carboxyl, literature, benzoic-acid class with substituents): approximately 4.2–4.6 depending on medium and ionic strength.
The morpholine nitrogen is typically weakly basic (pKaH ~ 7–8 for morpholine, literature), but aryl attachment can reduce basicity slightly.
Solubility profile (general behavior for such structures):
Water: low at neutral pH as the free acid; markedly increased in basic aqueous media (formation of carboxylate salt). Protonation of the morpholine nitrogen under acidic conditions can also increase aqueous solubility.
Organic solvents: typically soluble in polar aprotic solvents (DMSO, DMF, DMAc, NMP) and moderately soluble in alcohols and acetonitrile; limited solubility in nonpolar solvents.
Partitioning (qualitative): Aromatic carboxylic acids with a morpholine substituent often have cLogP in the ~1.5–2.5 range (literature/computational estimates), reflecting amphipathic character.
Melting point, boiling point, density, refractive index: Not specified for this item; consult primary literature or the CoA/Spec Sheet.
Note: All numerical ranges above are literature/general guidance only and are not Aladdin item specifications.
Quality and Grades
Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
Stabilizers/inhibitors: Not specified for this item; refer to CoA/Spec Sheet.
How to interpret grade in practice (general guidance)
When grade/purity is unspecified, assume a research reagent grade suitable for synthetic and screening applications. For trace-impurity-sensitive operations (e.g., catalytic cross-couplings, high-throughput screening), consult the CoA for detailed assay, residual solvent profile, and any metal content data.
If HPLC, LC–MS, or medicinal chemistry workflows are intended, request low-UV-absorbing solvent residues and confirm identity/purity by orthogonal methods (e.g., 1H NMR, LC–MS, HPLC area %, melting point).
Water/volatile content: Verify via Karl Fischer/LOD if moisture-sensitive steps are planned (e.g., acid chloride formation); specification is not provided for this item.
UV cutoff, metal limits, residual solvents: Not specified for this item; refer to CoA/Spec Sheet.
Batch-to-batch consistency: For scale-up or medicinal chemistry SAR campaigns, retain CoA and request representative spectra/chromatograms for each lot to ensure consistent performance.
Practical note
The presence of both an acid and a tertiary amine can complicate purity assessment due to salt formation with ambient CO2 or acids/bases; confirm the free-acid form or salt form as needed before use.
Reaction and Applications
As a bifunctional aromatic building block, 3-chloro-4-morpholinobenzoic acid combines a reactive carboxylic acid with an aryl chloride and a tertiary amine, enabling diverse transformations.
Carboxylic acid chemistry
Amide coupling: Conversion to amides with primary/secondary amines via carbodiimides (EDC/HOBt, DIC/Oxyma), uronium reagents (HATU, HBTU), CDI, or DMTMM. Useful for generating morpholinobenzamide motifs common in discovery chemistry.
Esterification: Fischer–Speier in alcohols with acid catalysis; Steglich esterification (DCC/DMAP) under mild conditions.
Acid chloride formation: SOCl2, (COCl)2 with catalytic DMF; enables subsequent acylations and Friedel–Crafts acylation on activated arenes.
Curtius/Schmidt pathways: Transform to acyl azide for isocyanate/urea/urethane synthesis (controlled conditions; safety first).
Decarboxylative couplings: Activation as N-hydroxyphthalimide (NHPI) ester for photoredox/Ni-catalyzed C–C/C–N formation (literature).
Aryl chloride handle
Cross-coupling: Suzuki–Miyaura (to install aryl/alkenyl groups), Buchwald–Hartwig amination (C–N), and Sonogashira (C–C) under Pd catalysis with appropriate ligands (e.g., XPhos/SPhos/BrettPhos for aryl chlorides). The para morpholine can enhance oxidative addition rates via electron donation.
Electrophilic aromatic substitution leveraging morpholine activation (directed metalation/electrophilic borylation) may be possible under tailored conditions.
Ionic-state leverage
Tunable solubility by pH: operate as free acid for organic-phase reactions; switch to carboxylate for phase-transfer or aqueous processing.
Representative applications (literature examples)
Library synthesis of morpholinobenzamides (EDC or HATU couplings) for kinase-targeted SAR.
Suzuki diversification at C-3 followed by amidation/esterification of the acid.
Note: Examples are general literature guidance; verify conditions with small-scale trials.
Reaction Conditions
General literature conditions for common transformations of 3-chloro-4-morpholinobenzoic acid (guidance only; not item specifications):
Amide coupling (free acid → amide)
Reagents: HATU (1.1–1.5 eq) or EDC·HCl (1.2–1.5 eq) + Oxyma/HOAt/HOBt; base DIPEA (2–4 eq).
Solvent: DMF, MeCN, DCM, or 2-MeTHF.
Temperature/time: 20–50 °C, 1–16 h.
Notes: If solubility is limiting, pre-form mixed anhydride or acid chloride. Keep water low for maximum conversion.
Esterification
Fischer: ROH (solvent, excess), catalytic H2SO4 or p-TsOH, reflux with Dean–Stark if applicable.
Steglich: DCC (1.1–1.3 eq), DMAP (0.1 eq), DCM/EtOAc, 0–25 °C.
Acid chloride formation
Reagents: SOCl2 (2–5 eq) or (COCl)2 (1.5–2 eq) with catalytic DMF.
Solvent: neat reagent or toluene/DCM; 0–70 °C, 1–4 h.
Caution: Exothermic HCl/SO2/CO evolution; use appropriate scrubbing.
Solvent: 1,4-dioxane/H2O (4:1) or toluene/H2O; 80–110 °C, 4–16 h.
Notes: Free acid can inhibit; protect as ester or add excess base/buffer.
Buchwald–Hartwig amination (on C-3)
Catalyst: Pd2(dba)3 (1–2 mol%) with BrettPhos/SPhos; base NaOtBu or Cs2CO3.
Solvent: toluene, CPME, or dioxane; 80–110 °C.
Decarboxylative coupling (via NHPI ester)
Catalysis: Ni/Pd with photoredox (Ir or organic dyes), blue LED, room temp to 40 °C.
Expected isolated yields vary widely (40–90%) depending on substrate/conditions. Always run small-scale screens to optimize ligand, base, and solvent for this specific scaffold.
Safety and Handling
Item-specific hazard information
GHS Classification: Not specified for this item; refer to SDS.
Signal Word: Not specified for this item; refer to SDS.
H-Statements: Not specified for this item; refer to SDS.
Pictograms: Not specified for this item; refer to SDS.
General laboratory safety guidance (literature/good practice; not item-specific)
Likely hazards: Aromatic carboxylic acids and tertiary amines can be irritants to skin, eyes, and respiratory tract. Dust may cause mechanical irritation.
Personal protective equipment: Use laboratory coat, safety glasses or goggles, and appropriate gloves (e.g., nitrile). Work in a fume hood to avoid inhalation of dust or vapors from solvents used for dissolution.
Handling: Avoid generating dust. Prevent contact with skin and eyes. Wash hands thoroughly after handling.
Incompatibilities: Strong oxidizing agents; strong bases and strong acids may cause decomposition or salt formation. Avoid acylation or chlorination reagents unless intended, as the carboxylic acid moiety is reactive.
Special considerations: The compound is not an ether solvent; peroxide formation is not a concern. As a bifunctional acid/base compound, it can form salts—avoid mixing with incompatible acids/bases without control.
First aid (overview):
Inhalation: Move to fresh air. Seek medical attention if symptoms persist.
Skin/eye contact: Rinse with plenty of water for at least 15 minutes; remove contaminated clothing.
Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
Spill response: Avoid dust. Collect mechanically; place in suitable container for disposal. Ventilate area.
Disposal: Dispose of contents/container in accordance with local/regional regulations.
Always consult the product’s SDS for authoritative hazard classification and response measures.
Solvent Selection
This product is a solid aromatic carboxylic acid with a tertiary amine substituent; solvent choice is typically driven by the intended operation (dissolution for screening vs. participation in coupling chemistry).
Polarity/miscibility (general behavior)
Readily dissolves in polar aprotic media: DMSO, DMF, NMP, DMAc.
Moderately soluble in MeOH/EtOH and MeCN; limited in nonpolar hydrocarbons and chlorinated solvents unless converted to an ester or acid chloride.
Aqueous media: poor solubility at neutral pH; solubility increases strongly above pH ~5 due to carboxylate formation; also increases below pH ~4 via morpholine protonation (forming a dicationic/zwitterionic species depending on pH).
Typical use scenarios
Biological screening stock solutions: DMSO (10–50 mM) with subsequent dilution into buffered media at pH > 7 to keep the acid deprotonated; include cosolvent to avoid precipitation.
Amidation/esterification: DMF, DCM, THF, 2-MeTHF, or MeCN depending on coupling system; ensure base compatibility.
Cross-coupling (using aryl chloride handle): toluene, dioxane, CPME, or mixed dioxane/H2O with appropriate base (K3PO4, Cs2CO3) and ligand system.
Selection guidance
Choose DMSO/DMF for maximum solubilization.
Use alcohols for Fischer esterification (water removal advantageous).
For greener profiles, consider 2-MeTHF or CPME instead of THF/DCM and Cyrene/GVL in place of DMF where feasible.
Note: No item-specific solubility specifications are provided; the above reflects general/literature behavior.
Storage and Reconstitution
Item-specific conditions (from Product Data)
Storage Conditions: Room temperature
Shipped In: Normal
General guidance (supplemental; not item specifications)
Stability: Aromatic carboxylic acids with morpholine substituents are typically stable solids under ambient conditions. Store tightly closed in a dry place, protected from excessive humidity and direct sunlight.
Packaging: Keep container tightly sealed to minimize moisture uptake and potential salt formation with ambient CO2 or acids/bases.
Reconstitution/solution preparation:
Analytical/screening stocks: Prepare in anhydrous DMSO at 10–50 mM. For aqueous use, adjust pH or use cosolvent to maintain solubility upon dilution.
Synthetic operations: If forming acid chlorides or using moisture-sensitive reagents, dry the solid under vacuum (e.g., 40–50 °C, several hours) prior to use.
Freeze–thaw: For DMSO stock solutions, aliquot to avoid repeated freeze–thaw cycles; store at −20 °C to −80 °C if long-term solution stability is required (verify stability by LC–MS/HPLC before critical use).
Shelf life: Not specified for this item; refer to CoA/Spec Sheet.
Research Use Note
For research use only. Not for human or veterinary use.
Structure and Identity
Brief description: 3-Chloro-4-morpholinobenzoic acid is an anilide-like aromatic carboxylic acid bearing a para-morpholinyl substituent and a meta-chloro handle, making it a bifunctional heteroaryl building block.
Item-specific identifiers (from Product Data)
SKU: C183292
CAS: 26586-20-9
InChIKey: 115387 (as provided; full-length standard InChIKey not specified)
SMILES: Not specified for this item; refer to CoA/Spec Sheet.
Literature/computed identity (for reference; not item-specific specs)
Preferred IUPAC-like name (literature): 3-chloro-4-(morpholin-4-yl)benzoic acid
Heteroatoms: one tertiary amine N and three O atoms (two from CO2H, one in morpholine), one Cl
Stereochemistry: achiral; no stereogenic centers
2D description: A benzene ring bearing a carboxylic acid at C-1, a chloro substituent at C-3 (meta to CO2H), and a morpholine ring attached through its nitrogen at C-4 (para to CO2H). The morpholine is a six-membered N,O-heterocycle [–N–(CH2–CH2–O–CH2–CH2)–].
Synthetic Utility
Key reactivity handles
Carboxylic acid (CO2H): Enables amide/ester formation, activation to acid chlorides/anhydrides, Curtius to isocyanates, and decarboxylative couplings after conversion to redox-active esters.
Aryl chloride (C–Cl at C-3): Entry point for Pd-catalyzed cross-coupling (Suzuki–Miyaura, Buchwald–Hartwig, Sonogashira) to diversify the scaffold.
Tertiary amino ether (morpholine): Modulates electronics (para activation), enhances solubility, and can engage in intramolecular H-bonding; it also provides a handle for quaternization if desired.
Strategic considerations in synthesis
Divergent synthesis: Two orthogonal vectors (C-3 and CO2H) allow late-stage diversification—couple first at C-3, then derivatize CO2H (or vice versa) to access matrices of analogs.
Chemoselectivity: Protecting the acid as an ester (e.g., methyl/tert-butyl) can improve solubility and compatibility with strong bases used in cross-coupling. Alternatively, perform coupling under buffered or in situ neutralization to avoid catalyst inhibition by the acid.
Directing/activation effects: The para morpholine donates electron density, often facilitating oxidative addition to aryl chloride under milder Pd–ligand systems compared to deactivated chlorobenzoic acids.
Utilizziamo i cookie per garantire il corretto funzionamento del sito web e, ove consentito, per migliorare la tua esperienza. Puoi gestire le tue preferenze in qualsiasi momento nelle Impostazioni. Per saperne di più, consulta la nostra Cookie Policy.
Desidera che le inviamo un messaggio quando avremo sconti disponibili?
Ricordamelo più tardi
Grazie! Controlli la sua casella di posta per confermare.
Products are supplied to verified businesses, institutions, and qualified professionals for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
