2-(3-Chlorophenoxy)ethanimidamide hydrochloride - Reagent grade

Cat. No.: C483250

GRADE & PURITY Reagent Grade

Storage

Room temperature

Specifications

Especificações e pureza

Reagent grade

Condições de armazenamento de armazenamento

Room temperature

Grau

Reagent Grade

Application Protocols

No validated bioassay or immunoassay protocols are provided for this item. As a synthetic building block, its use protocols are project-specific.

General handling suggestions:

• For stock solutions, dissolve the HCl salt in water, methanol, ethanol, or DMSO to a convenient concentration (e.g., 10–100 mM); filter if needed.
• For cross-coupling or base-mediated reactions, generate the free base prior to use and assess solubility in the intended organic solvent.
• Analytical QC in workflows typically includes 1H NMR, LC-MS, and HPLC purity checks after each transformation involving this building block.

Refer to the primary literature and your internal SOPs for reaction-specific procedures.

Biological Roles

Item-specific biological data are not provided for this product. The following is general background on amidine-containing small molecules (not specific to this item):

• Chemical biology relevance:
  • Amidines are strongly basic and cationic at physiological pH (as amidinium), which promotes binding to anionic biomolecules (e.g., carboxylates, phosphates) through electrostatic and hydrogen-bonding interactions.
  • Phenoxyaryl scaffolds are common motifs in chemical probes and materials interacting with membranes or proteins; the chlorine substituent modulates lipophilicity and electronic character.
• Permeability/solubility considerations (general):
  • Protonated amidines typically display high aqueous solubility but reduced passive membrane permeability unless balanced by hydrophobic substituents or delivered as neutral prodrugs.
• Enzymatic stability (general):
  • Amidines resist many amide-hydrolyzing enzymes due to different electronic structure, making them useful as amide bioisosteres in research compounds.
• Uses in assays/materials:
  • As cationic building blocks, amidines can be incorporated into polymers or surfaces for binding acidic biomolecules in affinity or capture workflows.

No claims are made regarding biological activity, safety in vivo, or clinical utility. For research use only, as stated by the manufacturer.

Buffer Applications

This compound is not a conventional buffering agent. Amidines are strongly basic, and the hydrochloride salt exists predominantly as an amidinium chloride in water, but it does not constitute a defined buffer system with a well-characterized pKa/pH working range like TRIS, HEPES, or phosphate.

Practical notes if used in aqueous systems:

• pH impact: Dissolving the HCl salt will acidify slightly due to chloride counterion from strong acid, while the amidinium remains cationic; do not rely on it to maintain pH.
• If pH control is needed, use a standard buffer (e.g., phosphate, acetate, TRIS) and simply dissolve this compound into that buffered medium at the desired ionic strength.
• Solubility: High aqueous solubility is likely for the salt; filter sterilization (0.22 µm) may be used for biological assays, ensuring compatibility with the assay matrix.

For robust buffering capabilities, select a dedicated buffer component; this product serves as a building block rather than a buffer.

Green Alternatives

This is a solid building block rather than a process solvent. Greener practice focuses on solvent and reagent choices in reactions/workups involving this compound.

Greener solvent options (literature-guided suggestions):

• Replace DMF/NMP/DMAc with:
  • 2-Methyltetrahydrofuran (2-MeTHF): Bio-derived, water-immiscible; good for Pd-couplings and extractions.
  • Ethyl acetate or isopropyl acetate: Low toxicity, readily recoverable; suitable for extractions and some couplings (with phase-transfer or after basification to free base).
  • Propylene carbonate or Cyrene (dihydrolevoglucosenone): Polar aprotic alternatives for certain coupling and substitution reactions.
• Aqueous media:
  • For salt handling and ion-exchange, water/EtOH mixtures can replace chlorinated solvents; employ surfactants or micellar catalysis (e.g., TPGS-750-M) for cross-coupling in water.

Trade-offs and notes:

• Amidines are basic and often require bases for reactions; choose inorganic bases with lower EHS impact (e.g., K2CO3, Na2CO3) over strong alkoxides where feasible.
• Catalyst loading: Modern Pd systems (e.g., XPhos precatalysts) allow ppm-level catalyst use, reducing metal waste; ensure proper metal scavenging in workup.
• Workup/waste minimization:
  • Utilize salt-switching crystallizations instead of chromatographic purifications when possible.
  • Favor aqueous extractions with greener esters over chlorinated solvents.

Always verify solubility and reaction efficiency when substituting greener media.

Pharmaceutical Uses

No pharmacopeial status or excipient role is provided for this item. It is offered for research and laboratory synthesis only.

General context for amidine hydrochlorides in formulation science (not specific to this item):

• Functionality: Amidines can serve as cationic motifs in research intermediates and may be explored as amide bioisosteres. However, their strong basicity and salt forms primarily categorize them as active building blocks rather than excipients.
• Solubility manipulation: Converting between free base and acid salts (HCl, mesylate, tosylate) is a common strategy to tune aqueous solubility and crystallinity during preformulation studies.
• Analytical handling: The cationic nature lends itself to reversed-phase LC with acidic mobile phases, or HILIC; ion-pair reagents may improve peak shape.

No therapeutic claims or uses are implied. Any application in drug product development would require independent assessment of purity, residual solvents, counterion stoichiometry, polymorphism, and stability, none of which are specified for this catalog item.

Physical Properties

Item-specific physical data: Not specified for this item; refer to CoA/Spec Sheet for definitive values (mp, water content, elemental analysis, etc.).

General/literature expectations for amidine hydrochloride salts (contextual, not item specifications):

• Physical state: Typically crystalline, hygroscopic solids; free bases are often oils or low-melting solids, but hydrochloride salts usually have higher melting points.
• Solubility profile:
  • Water: High to moderate solubility expected for amidinium chlorides due to cationic character.
  • Alcohols (MeOH, EtOH): Generally soluble to moderately soluble.
  • Polar aprotic solvents (DMSO, DMF): Usually freely soluble.
  • Nonpolar solvents (hexanes, toluene): Sparingly soluble.
• Acid–base properties (literature): Amidine conjugate acids have high basicity; typical pKaH of amidines ~11–13 (free base), meaning the hydrochloride salt is fully protonated in neutral media.
• Partitioning (qualitative): As an HCl salt, the compound is expected to be hydrophilic with low logP; converting to the free base can increase organic solubility for extractions.
• Hygroscopicity: Many amidine hydrochlorides are moisture sensitive and can absorb water; handle quickly in ambient humidity.

Refractive index, density, boiling/flash point (for solids) are not typically defined; no item-specific values are available for this product.

Quality and Grades

• Item grade: Reagent Grade (as specified for this catalog entry).
• What Reagent Grade implies:
  • Suitable for general laboratory synthesis and research applications where very low trace impurities and low UV background are not critical (unlike HPLC/LC-MS grades used as solvents or analytical reagents).
  • Typical controls include identity and purity by NMR/IR/HPLC or related methods, and acceptance criteria aligned with routine synthetic use. Exact impurity limits, water, and residual solvent specifications are Not specified for this item; refer to CoA/Spec Sheet.
• Stabilizers/additives: None stated; Not specified for this item. If stabilization against moisture is relevant, it will be declared on the CoA.
• Lot-to-lot documentation:
  • For structure-confirmed building blocks, vendors commonly provide HPLC purity, 1H NMR consistency, and sometimes elemental analysis. Request the CoA for your lot for specific numeric data.
• When to choose Reagent Grade for this compound:
  • Route scouting, medicinal chemistry SAR synthesis, heterocycle formation, and cross-coupling building-block use where downstream purification is planned.
  • For trace-analysis or bioanalytical calibration purposes, consider verifying background UV and metal content first (not provided here).

Reaction and Applications

As a chlorinated aryl ether bearing a protonated amidine (amidinium) functionality, this compound serves as a versatile building block.

• Cross-coupling on the aryl chloride (literature context):
  • Suzuki–Miyaura: Installation of aryl/hetaryl groups; requires activating ligands for aryl chlorides (e.g., XPhos/SPhos). Protecting or masking the amidine may be beneficial to avoid catalyst poisoning; salt form can sometimes be tolerated in polar solvents.
  • Buchwald–Hartwig amination or etherification: Formation of C–N or C–O bonds on the ring; strong bases may first liberate the free base from the HCl salt.
• Transformations at the amidine:
  • N-alkylation or acylation to form amidinium derivatives; can tune pKa and solubility of the scaffold.
  • Cyclizations: Condensation with α-haloketones/1,2-dicarbonyls can yield imidazoline/imidazole-type heterocycles (literature precedents for amidines).
  • Salt exchange: Conversion from HCl to alternative counterions (e.g., trifluoroacetate, tosylate) to modify handling and solubility.
• Applications in synthesis:
  • Useful in assembling cationic ligands/surface binders where strong electrostatic interactions are desired (e.g., immobilization on acidic supports, polymer modification).
  • Intermediate toward phenoxy-aryl frameworks where meta-chloro enables regioselective diversification by Pd-catalysis while the ether tether positions the amidine at a defined distance from the ring.
• Practical tips:
  • Drying: If hygroscopic, dry under high vacuum at ambient or mild temperature before moisture-sensitive reactions.
  • Degassing: For Pd-catalysis, standard inert techniques apply; chloride salts can alter catalyst speciation—ligand/catalyst screening is recommended.

Reaction Conditions

General, literature-style guidance for transformations relevant to aryl chlorides and amidines (not item-specific specifications):

• Suzuki–Miyaura coupling on aryl chloride:

  • Catalyst/ligand: Pd2(dba)3 (1–2 mol% Pd) with XPhos/SPhos (2–4 mol%), or commercially available precatalysts (e.g., XPhos Pd G3).
  • Base: K3PO4, K2CO3, or Cs2CO3 (2–3 equiv); aqueous or anhydrous.
  • Solvent: 2-MeTHF, toluene/H2O biphasic, dioxane/H2O, or EtOH/H2O.
  • Temperature/time: 70–110 C, 2–16 h.
  • Notes: Convert HCl salt to free base if basic media lower solubility; amidines may chelate Pd—ligand optimization advised.

• Buchwald–Hartwig amination (aryl chloride):

  • Catalyst/ligand: Pd(OAc)2 (1–3 mol%) + BrettPhos/XPhos; strong bases like NaOtBu or KOtBu (2–3 equiv).
  • Solvent: tBuOH, toluene, 1,4-dioxane, or 2-MeTHF.
  • 80–110 C; inert atmosphere.

• N-alkylation of amidines:

  • Base: Mild (e.g., DIPEA) with alkyl halides or sulfonates; polar solvents (MeCN, DMF, or acetone).
  • Monitor for over-alkylation; salt form may require pre-neutralization.

• Cyclization to imidazolines (generic amidine chemistry):

  • Condensation with α-haloketones under basic conditions in alcohols; 50–100 C.

Yields and conditions vary with substrate and protecting/activation strategies; small-scale screening is recommended. Always confirm compatibility of the amidine with bases/catalysts before scale-up.

Safety and Handling

Item-specific GHS details (signal word, H/P statements, pictograms): Not specified for this item; refer to the SDS for authoritative hazard classification.

General safety considerations for amidine hydrochloride salts (informational only):

• Likely hazards: Irritation to skin, eyes, and respiratory tract is common for basic, cationic organics and HCl salts. Dust may be irritating.
• PPE: Use lab coat, safety glasses or chemical splash goggles, and nitrile gloves. Handle powders in a fume hood to minimize inhalation of dust/aerosols.
• Handling practices:
  • Avoid breathing dust; prevent contact with skin/eyes.
  • Use clean, dry tools; close containers promptly to limit moisture uptake.
  • Prevent cross-contamination; dedicate spatulas/scoops for amine/amidine salts if performing trace-metal or acid-sensitive work.
• Incompatibilities (general): Strong oxidizers; strong bases (may liberate free base and HCl). Avoid mixing with acyl chlorides or isocyanates without proper control due to rapid exothermic reactions.
• First aid (summary; defer to SDS):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing; seek medical attention for persistent irritation.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Fire: Use CO2, dry chemical, or foam. Combustion may produce HCl and nitrogen oxides; firefighters should wear SCBA.

Solvent Selection

This product is a cationic organic salt (amidine·HCl). Solvent choice should balance solubility, base sensitivity, and downstream compatibility.

• Polarity and miscibility (general expectations):
  • Water: Often the best solvent for the HCl salt; facilitates ionization. Add minimal acid to suppress free-base precipitation if needed.
  • Alcohols (MeOH, EtOH, i-PrOH): Good solubility for many amidinium salts; convenient for workup and crystallizations.
  • DMSO/DMF: Excellent solvents for stock solutions and for coupling reactions; ensure dryness if base is present to avoid hydrolysis.
  • 2-MeTHF/EtOAc/toluene: Use after basifying to the free base or for extraction/partitioning steps.
• Practical tips:
  • To perform reactions under basic conditions or in nonpolar media, first convert the HCl salt to the free base (e.g., aqueous NaHCO3 or Na2CO3, then extract into an organic solvent). Validate phase behavior before scale-up.
  • For analytical prep (HPLC), aqueous buffers mixed with MeCN or MeOH are typically suitable due to the compound’s cationic nature; ion-pair reagents can improve peak shape if needed.
• Comparisons:
  • Versus primary amines: Amidines are more basic; salts are more water-soluble—plan purification accordingly.
  • Versus guanidines: Slightly less basic and often less hygroscopic, yet still strongly cationic in water.

Storage and Reconstitution

• Storage conditions (from Product Data): Room temperature.
• Shipping: Not specified for this item; refer to CoA/Spec Sheet.
• Container/atmosphere: Keep tightly closed in the original container with a desiccant if available. Amidinium salts can be hygroscopic; limit exposure to ambient humidity.
• Shelf life: Not specified for this item; monitor by HPLC/NMR for long-term projects.
• Reconstitution/solubility:
  • Aqueous: Dissolve directly in deionized water; if necessary, adjust pH slightly acidic to maintain the salt in solution.
  • Organic: Freely soluble in DMSO and DMF; soluble to moderately soluble in lower alcohols. For nonpolar media, convert to the free base and extract or dissolve in a more suitable solvent.
  • Sterile filtration: For biological assays, pass solutions through a 0.22 µm filter; prepare fresh aliquots to minimize degradation/contamination.
• Freeze–thaw: For DMSO/water stocks, prepare single-use aliquots and avoid repeated freeze–thaw cycles to prevent concentration changes from evaporation or moisture uptake.
• Disposal: Follow institutional and local regulations for organic salts; avoid release to drains. Consult the SDS for detailed guidance.

Structure and Identity

Item-specific identifiers (formula, exact mass, registries): Not specified for this item; refer to CoA/Spec Sheet.

General/literature description:

• Name: 2-(3-Chlorophenoxy)ethanimidamide hydrochloride (protonated amidine, chloride counterion)
• Core structural features:
  • An aryl ether: a 3-chlorophenyl ring linked via an oxygen to a –CH2–CH(=NH)–NH2 fragment (ethanimidamide, as the hydrochloride salt).
  • The amidine is protonated under HCl to an amidinium chloride, yielding a cationic center delocalized over C=N and the adjacent –NH2 group.
  • Aromatic ring substitution pattern: meta-chloro (3-chloro) relative to the phenoxy linkage.
• 2D description in words:
  • A benzene ring bearing chlorine at the meta position and an ether oxygen at the ipso position that connects to a –CH2–C(=NH)–NH2 chain. The cationic amidine nitrogen(s) are paired with a chloride anion in the solid state.
• Functional groups and reactivity highlights:
  • Strongly basic amidine (exists predominantly as amidinium in the HCl salt).
  • Ether linkage is generally stable to bases but can be cleaved under strong Lewis acidic conditions.
  • Aryl chloride suitable for Pd-catalyzed cross-coupling (Buchwald–Hartwig, Suzuki–Miyaura) with appropriate conditions and protection strategies as needed.
• Stereochemistry: None (achiral, no stereocenters).

Note: SMILES, InChI, InChIKey, molecular formula, and molecular weight are not provided for this catalog item; consult the product CoA/SDS for definitive identifiers.

Synthetic Utility

Key reactive elements present and how they can be leveraged in synthesis (general guidance):

• Aryl chloride handle (meta to phenoxy):
  • Cross-coupling platform: Enables diversification via Suzuki–Miyaura (C–C), Buchwald–Hartwig (C–N), or Kumada/Negishi couplings (with appropriate ligands for aryl chlorides). The phenoxy substituent tunes ring electronics; meta-chloro often requires more active catalysts.
• Amidine (as HCl salt):
  • N-functionalization: Alkylation/acylation to form amidinium derivatives; quaternization can provide permanently cationic species.
  • Condensations/cyclizations: Reaction with α-haloketones, orthoesters, or 1,2-dicarbonyls can provide imidazoline/imidazole and related heterocycles (documented for generic amidines).
  • Salt metathesis: Exchange chloride for alternative counterions to alter crystallinity and solubility, aiding isolation or formulation.
• Orthogonality and protection:
  • The basic amidine can coordinate to metals and inhibit catalysts. Temporary protection (e.g., as N-acyl amidinium, or converting to the free base and masking) may improve cross-coupling performance.
  • Ether linkage generally withstands bases but avoid strong Lewis acids that cleave aryl–O bonds.
• Synthesis planning:
  • This scaffold can serve as a node attaching a cationic side chain to a functionalized aryl ether core. Post-coupling manipulations on the amidine allow fine-tuning of pKa and solubility for material or probe development.

Target Specificity

Not applicable. This product is a small-molecule building block, not an antibody, enzyme, or affinity reagent. No target, epitope, clone, or species reactivity information is associated with this item.