N-(3,5-dichlorophenyl)guanidine , CAS No.46113-33-1

CAS: 46113-33-1 Cat. No.: N1020439 Formula: C₇H₇Cl₂N₃ Peso molecolare: 204.050

Storage

Room temperature

Specifications

Condizioni di conservazione di stoccaggio

Room temperature

Nomi e identificatori

• Sorrisi canonici: C1=C(C=C(C=C1Cl)Cl)N=C(N)N
• IUPAC Name: 2-(3,5-dichlorophenyl)guanidine
• InChIKey: PXNBOFBSFXZTES-UHFFFAOYSA-N
• INCHI: 1S/C7H7Cl2N3/c8-4-1-5(9)3-6(2-4)12-7(10)11/h1-3H,(H4,10,11,12)
• Peso molecolare: 204.050

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Benzene and substituted derivatives
      • Subclass Halobenzenes
        • Level5 Chlorobenzenes
          • Level6 Dichlorobenzenes

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Halobenzenes
• Intermediate Tree Nodes: Chlorobenzenes
• Direct Parent: Dichlorobenzenes
• Alternative Parents: Aryl chlorides Guanidines Propargyl-type 1,3-dipolar organic compounds Organochlorides Hydrocarbon derivatives
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: 1,3-dichlorobenzene - Aryl halide - Aryl chloride - Guanidine - Organic 1,3-dipolar compound - Propargyl-type 1,3-dipolar organic compound - Organic nitrogen compound - Hydrocarbon derivative - Organonitrogen compound - Organochloride - Organohalogen compound - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as dichlorobenzenes. These are compounds containing a benzene with exactly two chlorine atoms attached to it.
• 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: 204.050 g/mol
• XLogP3: 1.700
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 1
• Exact Mass: 203.002 Da
• Monoisotopic Mass: 203.002 Da
• Topological Polar Surface Area: 64.400 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 169.000
• 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

No validated bioassay or analytical application protocols are provided for this item.

General laboratory handling (literature/practice)

• Stock solution preparation: Dissolve in dry DMSO to prepare concentrated stocks (e.g., 10–50 mM). Filter (0.2 µm PTFE) if needed. Store aliquots to avoid repeated freeze–thaw.
• Synthetic use: For cross-coupling, consider protection of the guanidine (e.g., bis-Boc) prior to metal-catalyzed steps; after coupling, deprotect under acidic conditions (TFA, 0–25 °C) and neutralize to isolate the free base or form the desired salt.
• Purification: Reverse-phase preparative HPLC (for polar analogs) or normal-phase chromatography with basic modifiers (0.1–1% Et3N) can minimize tailing of basic compounds.

For any standardized or regulated workflow, develop and validate protocols internally. Refer to the CoA/Spec Sheet for any batch-specific notes.

Biological Roles

Item-specific biological/biochemical roles: None provided. This product is supplied for research use only.

General biochemical context (literature)

• Guanidinium functionality: The guanidinium group is strongly basic and can form multiple hydrogen bonds and ionic interactions with anionic biomolecules (e.g., phosphates, carboxylates). This underlies the widespread use of guanidine-containing motifs in biochemical probes and ligands.
• Aryl substitution: Incorporating a dichlorophenyl ring increases hydrophobic surface area and can modulate membrane affinity and binding in structure–activity explorations. However, specific biological targets or activities for N-(3,5-dichlorophenyl)guanidine are not stated here.
• Ionization: At physiological pH, guanidines are predominantly protonated, which can affect permeability and binding profiles; counterions and salt form strongly influence aqueous solubility.

Important: No medical, diagnostic, or therapeutic uses are implied or supported. For any in vitro biochemical experimentation, confirm solubility and protonation state in the chosen buffer system and evaluate nonspecific binding or aggregation empirically.

Buffer Applications

This material is not a conventional buffering agent. While guanidine hydrochloride is widely used as a protein denaturant and chaotrope, N-(3,5-dichlorophenyl)guanidine is a hydrophobic aryl guanidine and is not typically employed to set or maintain pH in biological buffers.

Practical note (literature/general)

• If solutions are prepared for biochemical assays, use standard buffers (e.g., phosphate, HEPES, Tris) and dissolve this compound first in a suitable co-solvent (commonly DMSO), then dilute into the buffer under vigorous mixing to avoid precipitation. Keep DMSO content minimal and consistent across controls.

No item-specific buffer recipes or pH ranges are provided for this product.

Green Alternatives

Although N-(3,5-dichlorophenyl)guanidine is not a solvent, greener choices can be made in the reactions and processing where it is used.

• Solvent selection (literature guidance)

  • Prefer bio-based ethers/esters (2-MeTHF, CPME, EtOAc) over chlorinated/higher-toxicity solvents when compatible with solubility and catalysis.
  • For Pd-catalyzed couplings, aqueous micellar catalysis (TPGS-750-M or similar) can reduce organic solvent use; assess guanidine protonation and surfactant compatibility.
  • Replace DMF/NMP with safer dipolar aprotics where feasible (e.g., propylene carbonate, Cyrene) acknowledging possible solubility/catalyst performance tradeoffs.

• Bases and reagents

  • Use carbonate bases (K2CO3, Cs2CO3) or organic bases with better EHS profiles (DIPEA) instead of stronger, hazardous bases when possible.
  • For acylations, EDCI/HOBt alternatives such as COMU or green carbodiimides can lower urea waste; consider catalytic coupling technologies.

• Process intensification

  • Continuous flow cross-couplings can reduce solvent volumes and improve heat/mass transfer, enabling lower loadings of catalyst and base.

Comparison snapshot (general; pros/cons depend on your transformation)

• 2-MeTHF vs dioxane: 2-MeTHF is renewable, higher boiling, and better EHS; dioxane has excellent miscibility but is a probable carcinogen.
• EtOAc vs DMF: EtOAc is greener and easy to remove; DMF offers superior solubilization and polarity for some couplings.

Always validate greener substitutions at small scale to confirm reactivity, selectivity, and isolation performance.

Pharmaceutical Uses

No pharmacopeial grade, excipient role, or GMP-related status is provided for this item; it is offered for research use only.

General formulation context (literature)

• Guanidine-containing research compounds are commonly handled as DMSO stock solutions for in vitro screening. Where solid formulations are needed, forming a mineral-acid salt (e.g., hydrochloride) can enhance water solubility and crystallinity relative to the free base.
• Compatibility considerations: Guanidines can interact with acidic excipients or reactive carbonyls; avoid excipients prone to acylation/iminyl reactions if stability studies are not performed.

Manufacturing/quality note

• Without a stated pharmacopeial monograph or GMP release, this product is not intended for use in drug product manufacturing. For any regulated application, inquire about custom synthesis and GMP-grade supply options.

All uses must remain within research and laboratory development contexts; no clinical applications are claimed or supported.

Physical Properties

Item-specific specifications

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight (catalog spec): Not specified for this item; refer to CoA/Spec Sheet.

Literature/general expectations for aryl guanidines (non-binding guidance)

• Physical state: typically crystalline solids owing to the guanidinium-centered H-bond network and aromatic stacking.
• Melting point: many N-aryl guanidines exhibit melting points in the ~150–220 °C range (literature ranges for related structures; specific value for this CAS not stated here).
• pKa: the conjugate acid (guanidinium) of aryl guanidines typically shows pKa ~12–13, somewhat attenuated vs aliphatic guanidines due to aryl substitution (literature).
• Solubility: generally sparingly soluble in nonpolar solvents; soluble/moderately soluble in polar aprotic media (DMSO, DMF, NMP) and in alcohols; water solubility can increase markedly as a mineral-acid salt (e.g., HCl) (literature).
• LogP/logS: chlorination increases lipophilicity vs unsubstituted phenylguanidines; exact values vary with protonation state and are not provided here (literature trend only).
• Spectroscopy: guanidine moiety shows characteristic strong IR bands near ~1650–1680 cm⁻¹ (C=N) and 3300–3400 cm⁻¹ (N–H stretches); 1H NMR typically shows downfield NH resonances with exchange broadening (literature patterns).

Important: Do not treat any of the above as product specifications. For regulatory or QC decisions, consult the item’s CoA/Spec Sheet.

Quality and Grades

Item-specific information

• 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 grades and implications (general)

• Research grade: In the absence of a stated analytical or pharmacopeial grade, materials are typically offered for research use. Such materials are suitable for discovery chemistry, method development, and non-GMP laboratory work. Trace-level attributes (e.g., water content, metals, residual solvents) are controlled per internal specifications but may not meet pharmacopeial monographs unless stated.
• Reporting and documentation: For chromatography-intensive applications or structure–activity studies, request the product’s CoA/Spec Sheet for batch-specific purity, residual solvent profile, and analytical data (HPLC/LC–MS, NMR, IR) as available.
• Stabilizer considerations: Guanidines generally do not require added stabilizers; however, they are hygroscopic to varying degrees depending on substitution. If the product includes any stabilizer or is supplied as a salt (e.g., hydrochloride), it will be disclosed on the CoA/label. None are specified here.
• Salt form vs free base: The free base and mineral-acid salts can differ in solubility and melting point. Confirm the supplied form on the label/CoA to ensure reproducible handling and assay calculations.

Recommendation: For sensitive catalytic applications or when trace metals are critical, contact us regarding low-metals or custom purification options.

Reaction and Applications

This compound is a functionalized guanidine bearing a 3,5-dichlorophenyl ring. It serves as both a strong organic base/nucleophile (at the guanidine) and as a dihalogenated aryl building block.

• Representative uses (literature)

  • Cross-coupling diversification at aryl–Cl positions: Suzuki–Miyaura, Buchwald–Hartwig, and (with more activated systems) Ullmann-type couplings to introduce aryl, amine, or heteroaryl groups at C–Cl. The 3,5-dichloro pattern enables selective mono- vs disubstitution under tuned conditions.
  • Acylation to acylguanidines: Reaction with acid chlorides or activated esters (e.g., EDCI/HOBt, HATU) affords acylguanidines, useful as ligands or intermediates.
  • Dehydration to aryl carbodiimides: POCl3, SOCl2, or CDI-mediated dehydrations can convert N-aryl guanidines to the corresponding aryl carbodiimides, which are valuable coupling agents or intermediates.
  • Heterocycle synthesis: Condensation of guanidines with 1,3-dielectrophiles (e.g., β-dicarbonyls, imidates) forms diaminopyrimidines, diaminotriazines, and related heterocycles.

• Practical tips (literature/practice)

  • Catalyst compatibility: Free guanidines can chelate or poison Pd/Cu catalysts. Consider temporary protection (e.g., Boc, Cbz, N,N′-bis-Boc) before cross-coupling, or use robust ligands (BrettPhos/XPhos) and stronger bases to maintain activity.
  • Protonation state control: Use non-nucleophilic bases (DIPEA, i-Pr2NEt) for acylations; acidify workups judiciously to partition between organic (free base) and aqueous (salt) layers.
  • Moisture management: While not highly hydrolysis-prone, maintain anhydrous conditions for coupling chemistry and acylations to maximize yields.

Note: The above are general literature applications to guide planning; optimize conditions for your substrate and consult primary sources.

Reaction Conditions

General literature conditions (optimize for your system; not item specifications)

• Suzuki–Miyaura coupling on aryl chloride sites

  • Catalyst/ligand: Pd2(dba)3 (0.5–1 mol% Pd) with bulky biaryl phosphines (SPhos/XPhos/BrettPhos), or precatalysts (BrettPhos Pd G3 1–2 mol%).
  • Base: K3PO4, Cs2CO3, or K2CO3 (2–3 equiv).
  • Solvent: 1,4-dioxane, toluene/H2O, or 2-MeTHF/H2O; 80–110 °C, 4–16 h.
  • Consider guanidine protection if catalyst deactivation is observed.

• Buchwald–Hartwig amination

  • Catalyst: Pd(OAc)2 or Pd-precatalyst (1–3 mol%) with BrettPhos/Josiphos-type ligands.
  • Base/solvent: NaOtBu or K3PO4; toluene, t-AmylOH, or dioxane; 80–110 °C.

• Acylation to acylguanidines

  • Reagents: acid chloride (1.1–1.5 equiv) or carboxylic acid with HATU/EDCI (1.1–1.5 equiv).
  • Base: DIPEA or i-Pr2NEt (2–3 equiv).
  • Solvent: DCM, DMF, or MeCN; 0–25 °C to control exotherm; 1–4 h typical.

• Dehydration to carbodiimide

  • Reagents: POCl3 or SOCl2 (3–5 equiv) with base (pyridine) or CDI (2–3 equiv) under anhydrous conditions.
  • Solvent: DCM, toluene, or THF; 0–80 °C depending on reagent; monitor by IR (N=C=N ~2110–2140 cm⁻¹).

• Heterocycle formation (e.g., diaminopyrimidines)

  • Combine with 1,3-dielectrophiles (activated β-dicarbonyls, imidates) in polar solvents (EtOH, DMF) with mild heating (50–100 °C); hours to overnight.

Notes

• Free vs salt form profoundly affects solubility and basicity; adjust base equivalents accordingly.
• Dry glassware/degassed solvents improve cross-coupling outcomes. Verify catalyst compatibility with free guanidines.

Safety and Handling

Item-specific hazard communication

• Signal word: Not specified for this item; refer to SDS.
• H-statements: Not specified for this item; refer to SDS.
• GHS classification and pictograms: Not specified for this item; refer to SDS.
• Storage conditions: Room temperature (per Product Data).

General safety considerations for aryl guanidines (literature/practice)

• Hazards: Guanidines are strong organic bases; many are skin/eye irritants and harmful if swallowed or inhaled. Dust may cause respiratory irritation. This compound should be handled to avoid contact and inhalation.
• PPE: Use appropriate lab attire: lab coat, safety glasses or goggles, and nitrile gloves. For solid handling, consider dust mask/respirator if airborne dust may form; work in a fume hood.
• Incompatibilities: Strong acids (will readily form salts with heat evolution), strong oxidizers, acylating agents, and carbonyl-activating chlorinating agents (e.g., oxalyl chloride, SOCl2) can react vigorously. Avoid contact with reactive halogenating agents.
• Engineering controls: Handle powders in a ventilated hood. Use antistatic measures to minimize dust.
• First aid overview (consult SDS for details):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin contact: Wash with soap and water; remove contaminated clothing.
  • Eye contact: Rinse cautiously with water for several minutes; remove contact lenses if present and easy to do; continue rinsing.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Spill/leak: Avoid dust generation; sweep up carefully and place in suitable waste container. Decontaminate surfaces with dilute detergent.

Always refer to the product-specific SDS for authoritative hazard classifications and response measures.

Solvent Selection

Applicability: As a basic, heteroatom-rich aromatic solid, solvent selection is primarily about dissolution for reaction or screening and managing protonation state.

• Polarity/miscibility profile (literature trends)

  • Preferred solvents for dissolution: DMSO, DMF, NMP, and alcohols (MeOH, EtOH) often dissolve aryl guanidines well due to H-bonding and polarity.
  • Limited solubility: Nonpolar solvents (hexanes, toluene) generally give low solubility for the free base.
  • Aqueous systems: Water solubility of the free base may be modest; forming the hydrochloride (or another mineral-acid salt) can substantially enhance aqueous solubility.

• Choosing between options

  • Bioassay stock solutions: DMSO stocks (e.g., 10–50 mM) are common; dilute into aqueous buffers immediately before use to minimize precipitation (literature practice).
  • Synthetic transformations: Polar aprotic media (DMF, DMAc, dioxane, NMP) are favored for cross-couplings on the 3,5-dichloroarene. Protect or buffer the guanidine if catalyst/base sensitive.
  • Crystallization/purification: Alcohols or alcohol/ether mixtures can be useful; salts (e.g., HCl, HBr) often crystallize readily from alcohol/ether systems.

• Comparison snapshot (general)

  • DMSO: Maximum solubilization power; high boiling; miscible with water.
  • DMF/NMP: Excellent for metal-catalyzed couplings; consider rigorous drying.
  • Alcohols: Facilitate salt formation, easier removal; may compete in acylation or H-bonding.

Note: No item-specific solubility specs are provided; verify experimentally and consult the CoA/Spec Sheet when available.

Storage and Reconstitution

Item-specific storage

• Storage conditions: Room temperature (per Product Data).
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

General guidance (literature/practice)

• Container: Store in a tightly closed, chemically compatible container with desiccant to limit moisture uptake. Protect from strong acids/oxidizers.
• Stability: Guanidine derivatives are generally stable solids under ambient, dry conditions. Avoid prolonged exposure to humidity and strong light.
• Reconstitution/solution preparation: For biochemical work, prepare DMSO stock solutions (e.g., 10–50 mM). For synthetic operations, dissolve in polar aprotic solvents (DMF, NMP) or alcohols as appropriate. If aqueous work is required, prepare a mineral-acid salt (e.g., dissolve in minimal HCl, then dilute) to enhance solubility.
• Freeze–thaw: Solid material is not affected by freeze–thaw. For solutions, store aliquots at low temperature (e.g., −20 °C for DMSO stocks) and minimize freeze–thaw cycles to prevent concentration drift from moisture ingress.

Always consult the product label and CoA/Spec Sheet for any batch-specific storage or stability instructions.

Structure and Identity

Brief overview: N-(3,5-dichlorophenyl)guanidine is an anilide-type guanidine in which the guanidinyl moiety is bound to a 3,5-dichlorophenyl ring. The molecule combines a strongly basic, hydrogen-bonding guanidine functionality with a dihalogenated aromatic handle suitable for cross-coupling diversification.

• Item-specific facts (from Product Data)

  • Product name: N-(3,5-dichlorophenyl)guanidine
  • CAS: 46113-33-1
  • PubChem CID: 12253688
  • Storage conditions: Room temperature
  • Research use: For research use only
  • InChIKey (catalog field): Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES (catalog field): Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular formula (catalog field): Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight (catalog field): Not specified for this item; refer to CoA/Spec Sheet.

• Literature identifiers and structural features (informational, non-specification)

  • Typical neutral free-base formula for N-aryl guanidines of this substitution: ~C7H7Cl2N3 (literature, for orientation)
  • Core functional groups: guanidine (–NH–C(=NH)–NH2), dihalogenated phenyl ring (3,5-dichloro)
  • Structural description (2D): a para- and ortho- relation-free 1,3,5-disubstituted benzene bearing chlorine atoms at positions 3 and 5; the aniline nitrogen at position 1 is substituted by a guanidinyl carbon (imino) bearing one terminal –NH2 and one –NH– linked to the ring.
  • Stereochemistry: achiral; no stereogenic centers.

Notes: All literature values here are provided for chemical context only; refer to the CoA/Spec Sheet for item-specific identifiers and release specifications.

Synthetic Utility

Functional elements and reactivity (literature)

• Guanidine core: Strong base/nucleophile capable of forming acylguanidines, thioureas/thioguanidines (with isothiocyanates), and imidoyl derivatives. Under dehydrating conditions, converts to carbodiimides.
• 3,5-Dichloroaryl handle: Two aryl chlorides positioned meta to each other enable regioselective cross-couplings. Chlorides are less reactive than bromides/iodides but can be transformed using modern Pd-catalysis.

Retrosynthetic value

• As a convergent intermediate, it allows late-stage diversification on the aryl ring while preserving the guanidine. Alternatively, protecting the guanidine enables even more aggressive cross-coupling conditions or lithiation chemistry on the aryl ring.

Transformations and named reactions

• Suzuki–Miyaura: Install aryl/heteroaryl boron partners at C–Cl.
• Buchwald–Hartwig amination: Introduce amines at C–Cl; requires strong ligands/catalysts (e.g., BrettPhos Pd G3) and careful base choice to avoid guanidine deactivation.
• Sandmeyer-type routes are not directly applicable here, but SNAr may be viable if additional ring activation is introduced.
• Acylation to acylguanidines via acid chlorides or activated esters (EDCI/HOBt, HATU) under non-nucleophilic base.
• Dehydration to aryl carbodiimide using POCl3/SOCl2 or CDI, then subsequent urea or amide couplings.

Practical notes

• Protecting groups: N,N′-bis-Boc guanidines are robust under Pd-catalyzed conditions; deprotect with TFA.
• Acid–base workup control is key to isolating free base vs salt and for improving extractive separations.

Target Specificity

No target specificity or immunochemical attributes are provided for this product.

• Item-specific test data (WB, IHC, IF, FC, kinetic targets, binding constants): Not specified for this item; refer to CoA/Spec Sheet.
• Context: This compound is a small-molecule building block, not an antibody or affinity reagent. Consequently, target specificity metrics (epitope, isotype, species reactivity) are not applicable.