d(-)-phenylglycinamide - Reagent grade

Cat. No.: D483116

GRADE & PURITY Reagent Grade

Storage

Room temperature

Specifications

Especificaciones y pureza

Reagent grade

Condiciones de almacenamiento de almacenamiento

Room temperature

Grado

Reagent Grade

Application Protocols

No vendor-tested biological assay protocols are provided for this small-molecule reagent. Typical usage depends on the synthetic or analytical objective (e.g., solution-phase coupling, protection/deprotection, crystallization via pH shift). For method development, consult standard peptide/amide coupling protocols and adjust solvent/pH based on solubility screening.

Biological Roles

• Endogenous status: d(-)-Phenylglycinamide is not a natural amino acid; it is an amide derivative of phenylglycine and does not have a known role in primary metabolism (literature).
• Biochemical interactions (literature/general):
  • As a cationizable α-amine adjacent to an aromatic ring, it may interact with amino acid transporters or enzymes as an analog, though such interactions are context-dependent and typically low-affinity without tailored substitution.
  • Amide functionality renders the carboxyl terminus non-ionizable under physiological pH, altering transport and recognition relative to D-phenylglycine.
• Utility in biochemistry: Often employed as a chiral building block or as a reference compound for structure–activity studies in peptide/peptidomimetic research, enzyme substrate specificity assays, or chiral recognition investigations.
• Note: No medical or clinical claims are made; for research use only (per Product Data).

Buffer Applications

This compound is not a standard buffer component. While the α-amine may confer weak buffering capacity around pH ~9–10 (literature expectation for α-amine pKa), d(-)-phenylglycinamide is not typically used to formulate laboratory buffer systems.

• Practical guidance: For buffer preparation in this pH region, dedicated buffering agents (e.g., Tris, CAPSO, CHES) are preferred. If used as a component in assay media, confirm pH stability empirically and do not rely on it as the primary buffer.

Green Alternatives

Greener choices center on solvent/coupling reagent selection rather than replacing the substrate itself.

• Solvent alternatives (literature-based comparison):

  • DMF/DMSO (traditional) vs 2-MeTHF/EtOAc/water–EtOH (greener). Using 2-MeTHF or EtOAc with an alcohol co-solvent can often replace DMF for acylation steps, improving EHS profiles and workup.
  • Aqueous media: For salt manipulations or enzymatic steps, water/ethanol mixtures can minimize VOCs.

• Coupling reagent selection:

  • Replace carbodiimide/HOBt systems with OxymaPure-based protocols (EDC/Oxyma) to reduce energy and safety concerns versus HOBt/HOAt. Enzymatic coupling (protease-mediated) in aqueous media is another route when applicable.

• Workup and isolation:

  • Favor pH-switch crystallizations from aqueous alcohols over chlorinated solvent triturations.

Small comparison (general literature):

• DMF: Excellent solvency; high boiling and regulatory scrutiny.
• 2-MeTHF: Bio-based, lower toxicity; may need co-solvent for complete dissolution.
• EtOAc/EtOH/water: Readily available, lower EHS impact; may lengthen reaction times or require catalyst optimization.

Pharmaceutical Uses

• Role: Not an excipient. Used in process chemistry as a chiral building block/intermediate toward D-phenylglycine–derived side chains and peptidomimetic scaffolds (literature). No therapeutic claims.
• Regulatory status: No pharmacopeial monograph is noted for this specific amide (literature). If materials are destined for GMP environments, vendor qualification and full quality packages (CoA, impurity profiles, residual solvents) are required.
• Formulation context: When used as an intermediate, typical operations include salt formation (e.g., hydrochloride) to aid handling and solubility, followed by protection/deprotection and coupling steps. Solvent and impurity carryover should be controlled per ICH Q3A/B, Q3C guidelines in downstream processes.

Physical Properties

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point: Not specified for this item; refer to CoA/Spec Sheet. (Amino amide solids of this class typically melt/decompose at elevated temperatures; literature values vary by enantiopurity and form.)
• Boiling point: Not meaningful (decomposes before boiling; literature).
• Density: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (qualitative, literature): Expected to be freely soluble in water and polar protic solvents (MeOH, EtOH) due to one cationizable amine and a hydrogen-bonding amide; sparingly soluble in nonpolar solvents (hexanes, toluene). Aqueous solubility increases in mildly acidic media (formation of ammonium salt) and may decrease near neutral-basic pH if extensive H-bonding leads to aggregation/crystallization.
• pKa (literature, α-NH3+/α-NH2): typically ~9–10 for α-amine in related phenylglycine derivatives; amide is non-basic (conjugate acid pKa ≲ –1). Exact values for this item not determined.
• LogP/logD (literature expectation): Low to moderate hydrophilicity (logP likely <1); exact value not specified for this item.
• Optical rotation: Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index: Not applicable to solids (literature).

Quality and Grades

• Grade: Reagent Grade (item-specific). This denotes suitability for general laboratory synthesis and analytical work where high purity is required, but it is not necessarily optimized for specialized applications such as HPLC-UV transparency screening or GMP manufacturing.
• What Reagent Grade implies:
  • Manufactured and packaged to meet general synthetic and preparative requirements.
  • Typical impurity controls include residual solvents/inorganics and stereochemical integrity where applicable; exact limits for this item: Not specified for this item; refer to CoA/Spec Sheet.
• Stabilizers/additives: None indicated; Not specified for this item; refer to CoA/Spec Sheet.
• Batch documentation: For chiral materials, inquire for CoA showing enantiomeric excess (ee), residual solvent profile, and water content (if determined). Item-specific values: Not specified for this item; refer to CoA/Spec Sheet.
• Suitability notes:
  • For stereosensitive syntheses, verify optical purity and absolute configuration on the provided CoA.
  • For chromatography-critical work, pre-test UV baseline and impurity profiles or consider a higher chromatographic grade if available.

Reaction and Applications

As a chiral α-amino amide adjacent to an aryl group, d(-)-phenylglycinamide is a versatile building block in asymmetric synthesis and peptide/amide chemistry.

• Representative applications (literature):
  • Peptide and peptidomimetic synthesis: Acts as an N-terminal amino component; amide handle allows further acylation or cyclization.
  • Side-chain precursor: Useful for constructing D-phenylglycine–derived motifs common in fine chemicals and as intermediates toward active side chains in antibiotic manufacturing (process chemistry context; no clinical claims).
  • Chiral pool approach: The D configuration can be transferred via transformations preserving stereochemistry (e.g., protection–functionalization sequences).
  • Formation of heterocycles: Intramolecular cyclizations (e.g., imidazolinones, oxazolines) from appropriately protected derivatives.
  • Resolution/derivatization: Chiral derivatizing agent (CDA) formation with carbonyls to analyze enantiopurity of complementary amines/aldehydes.
• Functional group reactivity:
  • α-Amine: Protect (Boc, Cbz, Fmoc) to control chemoselectivity; alkylate/acylate under standard conditions.
  • Amide: Generally inert; can be activated (e.g., to imidazolides) or participate in coupling after conversion to acid/activated species via hydrolysis–reacylation sequences.
• Practical tips:
  • Maintain stereochemical integrity by avoiding strong base and high temperatures; use mild coupling reagents (HATU, EDCI/HOBt or Oxyma) and low-temperature protocols.
  • For solubility, employ DMF, DMSO, or aqueous alcohols; protonation (pH 2–4) increases water solubility for processing.

Reaction Conditions

General literature guidance for α-amino amide chemistry (adjust for your specific substrate and target):

• Amide bond formation (as nucleophile at Nα):
  • Solvents: DMF, NMP, DCM, 2-MeTHF, or EtOAc with DMF co-solvent.
  • Reagents: HATU or TBTU (1.0–1.2 eq) with DIPEA (2–3 eq); or EDC·HCl (1.1–1.5 eq) + OxymaPure (1.1–1.5 eq) with DIPEA.
  • Temperature/time: 0–25 °C, 1–12 h; monitor by LC/MS. Avoid strong base and high heat to prevent racemization.
• Reductive amination (install substituent at N via carbonyl partner):
  • Solvent: MeOH, EtOH, or MeCN with acetic acid (catalytic) to form imine, followed by NaBH3CN or STAB.
  • Conditions: 0–25 °C; pH 5–6 favors iminium formation while minimizing amide hydrolysis.
• N-protection:
  • Boc2O (1.1–1.5 eq) in dioxane/water with NaHCO3 or in MeCN with DIPEA, 0–25 °C.
  • Cbz-Cl in biphasic Na2CO3(aq)/EtOAc; Fmoc-Cl in dioxane/water with base.
• Cyclizations to imidazolinones/oxazolines (from suitably functionalized derivatives):
  • Dehydrative conditions with CDI or SOCl2; 0–50 °C; inert atmosphere preferred.
• Notes on stereochemistry:
  • Use mild bases (DIPEA, NaHCO3) and low temperature to limit epimerization at the α-center.
  • Additives like Oxyma reduce racemization during couplings.

All values above are literature-type guidance; optimize per substrate. Item-specific specifications or tested methods: Not specified for this item; refer to CoA/Spec Sheet.

Safety and Handling

• GHS classification, signal word, pictograms, and H-statements: Not specified for this item; refer to the SDS for authoritative hazard information.
• General hazards (class knowledge): Low volatility solid; primary hazards typically relate to dust inhalation, eye/skin irritation, and potential sensitization common to amino acid derivatives. Avoid inhalation and contact.
• PPE: Laboratory coat, safety glasses, and appropriate chemical-resistant gloves (e.g., nitrile). Use a dust mask or work in a fume hood if handling powders.
• Incompatibilities (general): Strong oxidizers; strong acids/bases (may cause degradation or salt formation); acylation/alkylation reagents (reactive amine). Avoid moisture for best stability of fine powders.
• First aid (overview; defer to SDS):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: Rinse thoroughly with water for several minutes; remove contaminated clothing; obtain medical advice if irritation continues.
  • Ingestion: Rinse mouth; seek medical attention.
• Spills: Avoid dust formation; collect with inert absorbent; dispose per institutional and local regulations.
• Fire: Use water spray, CO2, dry chemical, or foam as appropriate for surrounding materials; combustion can produce COx and nitrogen-containing fumes.
• For research use only (per Product Data).

Solvent Selection

• Polarity and solubility profile (literature):
  • Highly polar and hydrogen-bonding; dissolves well in water (especially as the protonated amine salt) and polar protic solvents (MeOH, EtOH). Good solubility also expected in DMSO and DMF.
  • Poor solubility in nonpolar media (hexanes, heptane) and limited in moderately polar aprotics (EtOAc, MTBE) unless partially ionized or aided by co-solvents.
• Practical selection guidance:
  • For coupling or derivatization: DMF, NMP, or DCM/DMF mixtures are typical. For greener profiles, see 2-MeTHF, EtOAc, or Me-CPMO paired with an alcohol co-solvent if needed.
  • For salt formation or purification: Use aqueous alcohols; adjust pH to form ammonium salts to increase aqueous solubility.
  • For analytical prep: Aqueous buffers with acetonitrile or methanol as organic modifiers work well due to amphiphilicity.
• Comparison (literature-based):
  • Water/MeOH: Highest solubility; suitable for crystallizations via pH shift.
  • DMF/DMSO: Excellent solvent power for coupling; harder to remove.
  • 2-MeTHF/EtOAc: Greener options; may require co-solvent or warming to dissolve.

Storage and Reconstitution

• Storage (item-specific): Store at room temperature (per Product Data). Keep container tightly closed in a dry, well-ventilated place. Protect from excessive humidity to avoid caking or deliquescence.
• Shipping: Not specified for this item; refer to CoA/Spec Sheet.
• Stability: Amino amides are generally stable solids when dry and protected from light and heat; avoid prolonged exposure to strong acids/bases.
• Reconstitution/dissolution (general guidance):
  • Water or aqueous alcohols: Often readily soluble, especially upon slight acidification (e.g., 0.1–0.5% HCl) to form the ammonium salt.
  • Polar organics: DMF, DMSO, MeOH, EtOH typically dissolve readily. Warm gently (≤40 °C) and sonicate if needed.
  • Filtration: Use 0.2–0.45 µm PTFE or nylon filters for solution clarification.
• Freeze–thaw: Not applicable to solids; for prepared solutions, store aliquots refrigerated and avoid repeated freeze–thaw. Exact solution stability for this item: Not specified; determine empirically.
• For research use only (per Product Data).

Structure and Identity

d(-)-Phenylglycinamide is the amide derivative of the chiral amino acid phenylglycine, retaining the α-stereocenter and bearing both a primary amide (–CONH2) and a primary α-amine (–CH(NH2)–) adjacent to a phenyl ring.

• Item-specific identifiers (CAS, InChIKey, SMILES): Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula (literature): C8H10N2O
• Molecular weight (literature): ~150.18 g/mol
• Stereochemistry: Single stereogenic center at the α-carbon (D configuration as named; optical rotation sign is stated as “(–)” in the product name). Absolute configuration and [α]D for this item: Not specified; refer to CoA/Spec Sheet.
• Functional groups: Aromatic phenyl ring; α-amine; primary carboxamide. Capable of hydrogen bonding (donor and acceptor).
• 2D structural description (literature): A benzene ring (C6H5–) bonded to a chiral methine carbon bearing –NH2 and –CONH2 substituents (i.e., Ph–CH(NH2)–CONH2).

Synthetic Utility

• Functional handles:
  • Nα (primary amine): Amenable to protection (Boc, Cbz, Fmoc), acylation (amide bond formation), sulfonylation, reductive amination (on carbonyl partners), and urea/thiourea formation via isocyanate/isothiocyanate coupling.
  • Amide carbonyl: Typically inert; can be engaged after activation (e.g., to imidazolides) or leveraged in intramolecular cyclizations (to imidazolinones/oxazolines) with appropriate vicinal functionality.
  • Benzylic position (α to phenyl): Under careful conditions, can participate in oxidative or radical functionalizations when protected to prevent racemization (literature methods).
• Strategic roles:
  • Chiral pool starting material: Transfers the D configuration into target molecules with minimal chiral catalyst use.
  • Precursor to D-phenylglycine derivatives: Hydrolysis to the acid (under controlled conditions) followed by re-functionalization enables installation of diverse side chains.
  • Linker in peptidomimetics: The aryl group modulates lipophilicity and binding interactions, while the α-amino center provides points of diversification.
• Protecting-group strategy:
  • Boc protection favored for robust base stability and acid-labile deprotection.
  • For solid-phase applications, Fmoc protection enables base-labile deprotection with minimized racemization when using modern coupling additives (e.g., Oxyma/DIC).

Target Specificity

Not applicable. This product is a small-molecule reagent, not a biologic or antibody. No antigen/epitope or species reactivity information applies.