3,4-Difluorophenylalanine , CAS No.32133-36-1

CAS: 32133-36-1 Cat. No.: D1445678 분자식: C₉H₉F₂NO₂ 분자량: 201.18 EC 번호: 670-832-2 PubChem CID: 2737044

Storage

Store at 2-8°C

Shipped In

Wet ice

개요

3,4-Difluorophenylalanine is a fluorinated peptide with gelation ability.

Specifications

보관 조건

Store at 2-8°C

배송

Wet ice

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이름과 식별자

정식 스마일

C1=CC(=C(C=C1CC(C(=O)O)N)F)F

IUPAC Name

2-amino-3-(3,4-difluorophenyl)propanoic acid

InChIKey

PRAWYXDDKCVZTL-UHFFFAOYSA-N

INCHI

1S/C9H9F2NO2/c10-6-2-1-5(3-7(6)11)4-8(12)9(13)14/h1-3,8H,4,12H2,(H,13,14)

이성체 SMILES

C1=CC(=C(C=C1CC(C(=O)O)N)F)F

PubChem CID

2737044

분자량

201.18

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic acids and derivatives
    • 분류 Carboxylic acids and derivatives
      • Subclass Amino acids, peptides, and analogues
        • Level5 Amino acids and derivatives
          • Level6 Alpha amino acids and derivatives
            • Level7 Phenylalanine and derivatives

• Kingdom: Organic compounds
• Superclass: Organic acids and derivatives
• 분류: Carboxylic acids and derivatives
• Subclass: Amino acids, peptides, and analogues
• Intermediate Tree Nodes: Amino acids and derivatives - Alpha amino acids and derivatives
• Direct Parent: Phenylalanine and derivatives
• Alternative Parents: Phenylpropanoic acids Amphetamines and derivatives Alpha amino acids Fluorobenzenes Aralkylamines Aryl fluorides Amino acids Monocarboxylic acids and derivatives Carboxylic acids Organopnictogen compounds Organofluorides Organic oxides Monoalkylamines Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Phenylalanine or derivatives - 3-phenylpropanoic-acid - Alpha-amino acid - Amphetamine or derivatives - Aralkylamine - Fluorobenzene - Halobenzene - Aryl fluoride - Aryl halide - Monocyclic benzene moiety - Benzenoid - Amino acid - Carboxylic acid - Monocarboxylic acid or derivatives - Organic nitrogen compound - Organohalogen compound - Organofluoride - Primary aliphatic amine - Organonitrogen compound - Organooxygen compound - Primary amine - Carbonyl group - Hydrocarbon derivative - Organic oxide - Organopnictogen compound - Organic oxygen compound - Amine - Aromatic homomonocyclic compound
• 설명: This compound belongs to the class of organic compounds known as phenylalanine and derivatives. These are compounds containing phenylalanine or a derivative thereof resulting from reaction of phenylalanine at the amino group or the carboxy group, or from the replacement of any hydrogen of glycine by a heteroatom.
• 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

Application Protocols

No item-specific tested application protocols are provided. For general use:

• SPPS: Follow standard Fmoc/Boc peptide synthesis protocols with conditions adjusted for aromatic hydrophobic residues; see Reaction Conditions.
• 19F NMR studies: Prepare peptide/protein samples incorporating this residue; typical concentrations 0.1–2 mM in appropriate buffers, acquire 19F spectra with proton decoupling as needed. Exact parameters depend on instrument and sample.

For any specific assay or method, consult internal SOPs and validate conditions with small-scale trials.

Biological Roles

General biological context (no clinical claims)

• Phenylalanine analog: 3,4-Difluorophenylalanine is a noncanonical amino acid in which the aromatic side chain bears two fluorine atoms. This modification preserves the steric footprint of phenylalanine while altering electronics and hydrophobicity, enabling systematic exploration of aromatic interactions in proteins and peptides.
• 19F probe: Fluorine lacks background signals in biological systems, making 19F NMR a sensitive reporter of local environment, conformational changes, and ligand engagement when incorporated into proteins/peptides.
• Effects on structure/function: Electron-withdrawing fluorines reduce ring electron density, which can modulate cation–π and π–π interactions and potentially alter folding stability or binding energetics compared to native phenylalanine. Such effects are context dependent and are commonly assessed empirically.
• Enzymatic incorporation: While not a natural substrate for ribosomal synthesis, difluorophenylalanine residues can be introduced via chemical synthesis (SPPS) or, in specialized systems, by engineered tRNA synthetases in cell-free or cellular expression platforms. The item listing does not specify suitability for biological incorporation workflows—verify configuration and purity.

Usage notes

• Buffer compatibility: As with other amino acids, solubility increases when pH is moved away from the isoelectric point. For biological assays, prepare fresh solutions, filter sterilize, and confirm concentration spectroscopically or by quantitative NMR when precision is required.

Buffer Applications

This compound is not a standard buffering agent. As a zwitterionic amino acid, it can modestly contribute to buffering near its pKa values, but it is not typically used to prepare defined buffer systems.

Practical guidance (general)

• If dissolution is required in aqueous media, adjust pH to ~2–3 (to protonate the amine) or ~9–10 (to deprotonate the carboxylate) to increase solubility, then back-titrate to the working pH after complete dissolution.
• For analytical/sample preparation, conventional buffers (phosphate, HEPES, acetate, Tris) should be used for pH control; add 3,4-difluorophenylalanine as a solute or component as needed.

Green Alternatives

Greener choices focus on solvent and reagent selection rather than on the amino acid itself.

Comparison (general guidance)

• DMF vs. alternatives: DMF is effective for SPPS but has environmental/health concerns.
  • Possible alternatives: NBP (N-butyl-2-pyrrolidone), PC (propyl/propylene carbonate), or bio-based solvents (e.g., Cyrene) have been explored for peptide coupling and resin swelling in certain contexts. Validate compatibility with your resin and coupling system.
• Coupling reagents:
  • Conventional: HATU/HBTU (effective but safety concerns with aza-uroniuim wastes).
  • Greener trend: Use DIC or EDC with OxymaPure or ethyl cyano(hydroxyimino)acetate; minimize excess reagents; implement in situ activation to reduce waste.
• Aqueous routes: For solution-phase work, dissolve by pH adjustment in water where possible; neutralize after dissolution to target conditions. This reduces reliance on dipolar aprotic solvents.

Trade-offs

• Resin compatibility and coupling efficiency may be lower with some greener solvents; minor temperature elevation or longer coupling times may be needed.
• Analytical handling in water-rich media may require anti-oxidants or microbial controls for longer campaigns.

Bottom line

• Start with water (pH-adjusted) when feasible; if SPPS demands strong solvation, evaluate NBP/PC/Cyrene as partial or full DMF replacements using small-scale trials.

Pharmaceutical Uses

No pharmacopeial or excipient grade is claimed for this item.

General formulation/manufacturing context (non-therapeutic claims)

• Building block: Employed in the synthesis of fluorinated peptides and peptidomimetics to enhance metabolic stability or modulate receptor interactions during preclinical research.
• Analytical standard: May be used as a reference material in method development for fluorinated amino acids (e.g., LC–MS quantitation). Purity, enantiomeric composition, and counter-ions (if any) should be verified by CoA.

Notes

• For any application approaching GMP or clinical manufacturing, source a qualified grade with full regulatory documentation. This listing provides research use only.

Physical Properties

Item-specific specifications

• 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 unprotected 3,4-difluorophenylalanine; informational only)

• Approximate formula: C9H9F2NO2; MW ~201.17 g/mol.
• Acid–base: Zwitterionic near neutrality; typical α-CO2H pKa1 ~2.0–2.4, α-NH3+ pKa2 ~8.8–9.5 (literature ranges for phenylalanine analogs; ring fluorination may slightly acidify). Isoelectric point (pI) expected in the ~5.5–6.0 range.
• Solubility: Like many hydrophobic aromatic amino acids, sparingly soluble in neutral water but soluble upon adjustment to acidic (formation of ammonium salt) or basic pH (carboxylate salt). Often insoluble in nonpolar organic solvents; moderately dispersible in polar aprotic media with base (e.g., DMF/DMSO) for coupling.
• LogP: Ring fluorination increases lipophilicity relative to phenylalanine; expect modestly higher logP (literature trend); exact value not widely reported.
• Optical rotation: Enantiomer-dependent; not applicable if racemic.
• Melting point, density, refractive index: Not well-established in public literature for this specific difluoro regioisomer in unprotected form.

Practical notes

• Hygroscopicity can be moderate for free amino acids; handle quickly on the bench, cap promptly, and store desiccated when possible.

Quality and Grades

Item-specific information

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

Context and expectations

• Amino acid building blocks are typically offered as free acid/base forms or with protecting groups for peptide synthesis (e.g., Fmoc-3,4-difluorophenylalanine). Because no protection or enantiopurity is specified here, confirm whether the product is L-, D-, or DL- and whether it is unprotected or protected before planning SPPS or biochemistry workflows.
• Typical quality controls for such materials include: enantiomeric excess (chiral HPLC), assay purity (HPLC), identity (1H/13C/19F NMR, MS), water content (KF), and residual solvents/metals. For this listing, specific numerical specifications are not provided.

Implications for use

• Chromatographic applications (e.g., analytical standards) benefit from high assay purity and well-characterized residuals; verify by CoA.
• Peptide synthesis: Enantiopurity and low racemization propensity are critical. Confirm ee and any stabilizers/additives.

Documentation

• For exact specs, refer to the item’s CoA/Spec Sheet and SDS. If regulatory/compendial status (e.g., JP/Ph. Eur./USP) is required, request documentation—no pharmacopeial grade is claimed here.

Reaction and Applications

Application domains (general, literature)

• Peptide chemistry: Incorporation of 3,4-difluorophenylalanine into peptides by SPPS (Fmoc/Boc strategies) to modulate hydrophobicity, aromatic interactions, and protease resistance. The difluoro motif provides a 19F-NMR probe without significantly altering sterics compared to phenylalanine.
• Biophysical probes: 19F NMR labeling to study protein folding, ligand binding, and local environment polarity; the two ring fluorines improve signal while maintaining compact size.
• Medicinal chemistry: As a building block in peptidomimetics and small molecules to tune pKa, metabolic stability, and binding through halogen effects.

Reaction families and notes

• Amide bond formation: Standard coupling (HATU/HBTU/DIC+Oxyma/EDC) between the α-amine/α-carboxyl and partners; no side-chain protection needed for the difluorophenyl ring.
• Protection strategies: If supplied as free amino acid, convert to Fmoc- or Boc-protected derivatives for SPPS. Enantiopure L-form is typically used in ribosomal peptides; confirm configuration.
• Derivatization: Esterification of the carboxyl (MeOH/HCl or TMS-diazomethane) for analytical methods; N-acylation for prodrugs or intermediates.
• Cross-coupling on aryl-F is generally not feasible; the aryl fluorines are inert under standard Pd-catalyzed conditions—use prefunctionalized analogs if further ring modification is desired.

Practical tips

• Dry solvents/reagents minimize side reactions during coupling. Pre-dissolve in DMF or NMP; gentle heating (30–40°C) can aid dissolution. Monitor for racemization under strongly basic or prolonged activation conditions; Oxyma-based protocols help suppress epimerization.

Reaction Conditions

General guidance (literature/practice)

• SPPS (Fmoc strategy):
  • Solvent: DMF or NBP; resin: Rink Amide or Wang, swollen in DMF/DCM.
  • Deprotection: 20% piperidine in DMF (or 2% DBU/2% piperidine variants) for 5–20 min cycles.
  • Coupling: 3–5 eq amino acid, 3–4 eq HATU or DIC, 3–5 eq DIPEA or 1–2 eq Oxyma/DIC; 30–60 min at RT. Double coupling or mild heating (35–45°C) can improve difficult insertions.
  • Capping: Ac2O/DIPEA in DMF to block unreacted amines.
  • Cleavage (if protected): TFA-based cocktails (e.g., 95% TFA with scavengers) 1–3 h, then precipitate in cold ether.
• Solution-phase coupling:
  • Solvent: DMF, DCM/DMF, or MeCN/water with EDC/Oxyma.
  • Temperature: 0–25°C typical; monitor for epimerization—avoid prolonged preactivation.
• Racemization control: Employ Oxyma or HOAt-derived additives; maintain lower temperatures; minimize base equivalents and activation times.
• Purification: Reverse-phase HPLC is effective; monitor by UV (210–220 nm) and 19F NMR.

Expected outcomes (typical literature ranges)

• Coupling yields per step typically >95% in optimized SPPS; overall isolated peptide yields depend on length and sequence. For small-molecule amide couplings, 70–95% isolated yields are common under optimized conditions.

Note: These are general literature conditions; adjust to your resin, scale, and instrumentation.

Safety and Handling

Item-specific hazard data

• GHS classification, signal word, pictograms, and H-statements: Not specified for this item; refer to SDS.
• Storage: Store at 2-8°C. Shipped on wet ice.

General safety guidance (literature/practice for amino acids and fluorinated aromatics; consult SDS for authoritative instructions)

• Expected hazards: Low volatility solid; dust may cause mechanical irritation to eyes/respiratory tract. No specific acute toxicity information provided for this item.
• PPE: Laboratory coat, safety glasses/goggles, and appropriate gloves (e.g., nitrile). Use in a fume hood when weighing fine powders to minimize dust exposure.
• Incompatibilities: Strong oxidizers and strong acids/bases may cause decomposition; avoid contact until dissolved and pH-adjusted appropriately. Avoid reactive acylating agents unless intended for derivatization.
• Good hygiene: Avoid inhalation of dust, ingestion, or skin contact. Wash thoroughly after handling.
• First aid (general): Eye contact—rinse with water for several minutes; Skin—wash with soap and water; Inhalation—move to fresh air; Ingestion—rinse mouth. Seek medical attention if symptoms persist.
• Waste: Dispose according to institutional and local regulations for organic laboratory solids.

Special notes

• No data on sensitization or environmental hazards are provided here. Always review the product-specific SDS before first use.

Solvent Selection

General solvent behavior (literature/practice)

• Polarity/class: Zwitterionic amino acid; hydrophilic backbone with a moderately lipophilic 3,4-difluorophenyl side chain.
• Miscibility profile:
  • Water: Limited solubility near neutral pH; dissolves better under acidic (NH3+ form) or basic (carboxylate) conditions.
  • Polar aprotic: DMF, DMSO, NMP can solubilize upon gentle warming and/or with base or coupling reagents—common for SPPS.
  • Alcohols: Methanol/ethanol provide limited solubility; use with acid/base adjustment.
  • Nonpolar solvents (hexanes, toluene): Poorly soluble.

When to choose which solvent

• Aqueous buffers: Use for biochemical assays; adjust pH to 2–3 or 9–10 for higher solubility; return to target pH after dissolution.
• SPPS: DMF or NMP are standard. DCM may be used for swell/wash of resins but typically not for dissolving the amino acid itself unless protected and more lipophilic.
• LC method development: Water/acetonitrile (or methanol) with appropriate buffers; 19F-containing aromatics often show strong UV at 210–220 nm.

Small comparison (general)

• Water (pH-adjusted): Greenest option, best for biological work.
• DMF/NMP: Highest solubilizing power for coupling steps; consider greener alternatives if feasible (see Green Alternatives).
• DMSO: Good for stock solutions; compatible with many assays but can affect biological systems at high percentages.

Storage and Reconstitution

Item-specific facts

• Storage conditions: Store at 2-8°C.
• Shipped in: Wet ice.

General handling guidance

• Keep container tightly closed. Protect from moisture; store in a desiccator if possible to maintain consistent weight and performance.
• Avoid repeated warming/cooling cycles; dispense into working aliquots if frequent use is anticipated.

Reconstitution and solution preparation (general)

• Aqueous: To prepare concentrated stocks, adjust water to pH ~2–3 (e.g., dilute HCl) or ~9–10 (e.g., dilute NaOH) before adding the solid to enhance dissolution. After full dissolution, back-titrate to the desired pH. Filter sterilize (0.22 µm) for biological work.
• Organic: For SPPS/derivatization, dissolve in dry DMF/DMSO/NMP; gentle warming (≤40°C) and sonication can help. Prepare fresh solutions for coupling.
• Storage of solutions: Aqueous solutions are best used fresh or stored short-term at 2–8°C. For longer storage, freeze at −20°C or below in aliquots; avoid multiple freeze–thaw cycles.

Note

• Exact concentration limits, stability in solution, and water/residual solvent specs are not provided for this item; refer to the CoA/Spec Sheet and perform small-scale stability checks as needed.

Structure and Identity

Item-specific facts (from Product Data)

• Product name: 3,4-Difluorophenylalanine (SKU D1445678)
• CAS: 32133-36-1
• CID: 2737044
• InChIKey: 284870 (as provided)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Storage: Store at 2-8°C; shipped on wet ice.

Literature/general structural information

• Compound type: Noncanonical aromatic amino acid; phenylalanine analog bearing two fluorine atoms on the benzene ring at the 3- and 4-positions.
• Likely structural features: An α-amino acid backbone (–CH(NH2)–CO2H) attached to a 3,4-difluorophenyl side chain via –CH2–. Stereochemistry at the α-carbon may exist (D/L); unless specified, material may be racemic or a defined enantiomer—verify on CoA.
• Functional groups: Primary amine (basic), carboxylic acid (acidic), aromatic ring with two electron-withdrawing fluorine substituents.
• 2D description (words): A benzenoid ring bearing fluorines at meta and para relative to the benzylic methylene; that methylene connects to a chiral α-carbon bearing an amino group and a carboxyl group.
• Molecular formula (literature/computed): C9H9F2NO2 (for the free amino acid, no protecting groups).
• Molecular weight (literature/computed): ~201.17 g/mol.

Notes

• Isomeric form (D, L, or DL) and presence/absence of protecting groups (e.g., Fmoc-, Boc-) are not specified for this item; verify prior to use.

Synthetic Utility

Strategic roles

• Aromatic, electron-deficient side chain: The 3,4-difluoro substitution fine-tunes π-stacking and cation–π interactions in peptide SAR studies while minimally altering sterics versus Phe.
• 19F handles: Built-in NMR tag(s) for conformational/interaction studies without additional labeling steps.

Transformations

• Amide couplings: Standard peptide bond formation at the α-amine/α-carboxyl. Use Fmoc/Boc protection as appropriate; no side-chain protection needed for the aryl difluoro ring.
• Ester/amide derivatives: Prepare methyl/ethyl esters for resolution or analytical derivatization; N-acyl, N-carbamate variants for protecting group strategies.
• Chiral resolution: If supplied racemic, resolution via diastereomeric salt formation or chiral HPLC.
• Late-stage modification: The aryl–F bonds are robust and generally inert; oxidative or electrophilic aromatic substitutions are deactivated. Plan synthetic routes accordingly—introduce additional ring functionality before fluorination or use other regioisomers with halogen/boronate handles.

Retrosynthetic value

• Serves as a convergent point in peptide assembly to probe position-specific effects. Compatible with standard SPPS resins (Wang, Rink Amide) once protected and activated. Electronic withdrawal can slightly influence coupling kinetics; ensure sufficient activation times.

Analytical

• 1H/13C/19F NMR, LC–MS, and chiral HPLC are routine for ID, purity, and ee. 19F signals provide straightforward tracking of incorporation and purity.

Target Specificity

Not applicable. This product is a small-molecule amino acid building block, not an antibody or affinity reagent. No target/epitope specificity is associated. Refer to Reaction & Applications and Synthetic Utility for relevant usage details.

자주 묻는 질문

How should this product be stored?

Store at 2–8 °C. Refrigerated storage is required to maintain the specified shelf life.

How is this product shipped?

This product ships chilled on wet ice. Unpack on arrival and transfer it to the storage condition stated above.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 32133-36-1, the molecular formula is C9H9F2NO2, and the molecular weight is 201.18 g/mol. InChIKey PRAWYXDDKCVZTL-UHFFFAOYSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.