Uracil-4-acetic acid - ≥96% , CAS No.4628-39-1

CAS: 4628-39-1 Cat. No.: U1073465 Formula: C₆H₆N₂O₄ Peso molecolare: 170.12 Numero EC: 863-849-3 PubChem CID: 73271

GRADE & PURITY ≥96%

Storage

Room temperature

Specifications

Specifiche e purezza

≥96%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥96%

Nomi e identificatori

Sorrisi canonici

C1=C(NC(=O)NC1=O)CC(=O)O

IUPAC Name

2-(2,4-dioxo-1H-pyrimidin-6-yl)acetic acid

InChIKey

NQAUNZZEYKWTHM-UHFFFAOYSA-N

INCHI

1S/C6H6N2O4/c9-4-1-3(2-5(10)11)7-6(12)8-4/h1H,2H2,(H,10,11)(H2,7,8,9,12)

Isomeri SMILES

C1=C(NC(=O)NC1=O)CC(=O)O

PubChem CID

73271

Peso molecolare

170.12

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Diazines
      • Subclass Pyrimidines and pyrimidine derivatives

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Diazines
• Subclass: Pyrimidines and pyrimidine derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Hydroxypyrimidines
• Alternative Parents: Heteroaromatic compounds Monocarboxylic acids and derivatives Carboxylic acids Azacyclic compounds Organopnictogen compounds Organonitrogen compounds Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Hydroxypyrimidine - Heteroaromatic compound - Azacycle - Monocarboxylic acid or derivatives - Carboxylic acid - Carboxylic acid derivative - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Carbonyl group - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as hydroxypyrimidines. These are organic compounds containing a hydroxyl group attached to a pyrimidine ring. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
• External Descriptors: monocarboxylic acid

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: 170.120 g/mol
• XLogP3: -1.700
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 2
• Exact Mass: 170.033 Da
• Monoisotopic Mass: 170.033 Da
• Topological Polar Surface Area: 95.500 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 281.000
• 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 vendor-tested biological assay protocols are specified for this item. Typical laboratory uses are synthetic and preparative. General, literature-based examples include:

• Preparation of an NHS ester for amine coupling:

  • Dissolve uracil-4-acetic acid (e.g., 0.1 mmol) in dry DMF (1 mL). Add NHS (0.12–0.15 mmol) and EDC·HCl (0.12–0.15 mmol) at 0–5°C, then stir 1–2 h at rt. Use immediately or store aliquots at −20°C (anhydrous) to minimize hydrolysis. Couple to amine-bearing substrates in PBS (pH 7.5–8.5) with 10–20% DMF co-solvent.

• Amide coupling to a resin-bound amine (solid-phase):

  • Swell amine resin in DMF, pre-activate the acid with HATU (1.1–1.5 eq) and DIPEA (2–3 eq) in DMF, then add to resin and agitate 1–2 h. Cap unreacted amines (Ac2O/DIPEA), wash, and cleave per resin protocol.

• Aqueous stock preparation (analytical use):

  • Prepare 10–50 mM stock in 0.1 M NaOH or Tris base, then adjust to the working buffer with minimal DMSO (≤5–10%) if needed to maintain solubility.

These are illustrative, literature-style procedures. Optimize conditions for your substrates and instrumentation. No application-specific validation data are provided for this SKU.

Biological Roles

• General context (literature):

  • Uracil is one of the four canonical RNA nucleobases (pyrimidine-2,4-dione), participating in Watson–Crick base pairing with adenine in RNA. Derivatives such as uracil-4-acetic acid maintain the uracil recognition features (ring carbonyls and N–H donors/acceptors) while introducing a carboxymethyl group for conjugation.
  • Such derivatives are used to probe nucleic acid–protein interactions, RNA-binding domains, and hydrogen-bonding motifs in biochemical systems. The carboxylic acid facilitates immobilization on matrices or coupling to fluorophores/affinity tags.

• Enzymatic and binding considerations:

  • Uracil-recognizing proteins (e.g., uracil-DNA glycosylases) and RNA-binding proteins may interact with substituted uracils depending on substitution position and ionization state. Steric and electronic effects from the acetic acid moiety can modulate affinity.
  • In aqueous buffers near neutral pH, the acid may be partially ionized depending on pKa, influencing uptake into active sites and nonspecific binding to proteins.

• Use in biochemical assays (research use only):

  • As a hapten for generating anti-uracil binding reagents (screening), or as a competitor/ligand in binding assays to evaluate uracil-recognition.
  • As a handle to prepare uracil-bearing probes for RNA-focused pull-downs or surface plasmon resonance studies after coupling to sensor chips.

Note: No clinical or therapeutic claims are made; applicability depends on assay design, substitution pattern, and purity. Validate biological interactions empirically for your system.

Buffer Applications

This compound is not a classical buffering agent. It lacks a conjugate acid/base pair with a suitable pKa spacing to act as a primary buffer across a wide pH range.

• Practical notes (general):
  • Solubility in aqueous media improves above the carboxylic acid pKa where the carboxylate forms. To prepare aqueous solutions, dissolve in a small volume of base (e.g., NaOH, pH > pKa) and adjust with a standard buffer (e.g., phosphate, HEPES, Tris) to the desired pH.
  • For bioconjugation, conduct EDC/NHS activation in mildly acidic buffers (MES, pH 5.0–6.5) to stabilize the O-acylisourea/NHS ester, then couple to amines in phosphate/borate buffers at pH 7.5–8.5.

If a buffering system is required, select a dedicated buffer (phosphate, HEPES, MOPS, borate) appropriate to your target pH and ionic strength. This product functions as a reactant/ligand rather than a buffer.

Green Alternatives

While the molecule itself is a solid building block, greener practices focus on solvent systems and coupling reagents.

• Greener solvent choices (literature/general):

  • Replace DMF/NMP where possible with:
    • 2-Methyltetrahydrofuran (2-MeTHF) or CPME for esterifications and extractions (lower toxicity, better recyclability).
    • Propylene carbonate or ethyl acetate as medium-polarity alternatives for certain couplings.
    • Aqueous micellar media (e.g., TPGS-750-M) for amide bond formation with reduced organic solvent usage.

• Coupling reagent considerations:

  • Use water-soluble carbodiimides (EDC) in buffered aqueous/EtOAc biphasic systems to minimize polar aprotic solvents.
  • Enabling catalysts like DMAP can be replaced or minimized by using organocatalysts compatible with green media; enzyme-catalyzed esterifications are possible for selected alcohol partners.

• Small comparison (general):

  • DMF vs 2-MeTHF: DMF offers superior polarity for dissolving uracil acids; 2-MeTHF is greener but may require a co-solvent or mild base to achieve comparable solubility.
  • DCM vs EtOAc: EtOAc is a safer, greener extraction/column solvent; often sufficient for workups and flash chromatography when polarity is managed via acid/base modulation.

• Waste minimization:

  • Exploit acid/base partitioning to avoid chromatographic purification (salt formation–reprotonation cycles).
  • Recycle mother liquors where feasible; use minimal equivalents of coupling reagents and consider on-water protocols.

Trade-offs: greener media may reduce solubility of this polar heteroaromatic; monitor reaction rates and adjust temperature, concentration, or base accordingly.

Pharmaceutical Uses

• Role in formulation (general; no therapeutic claims):

  • As a carboxylic acid-bearing nucleobase analogue, uracil-4-acetic acid can serve as a synthetic intermediate toward nucleoside/nucleotide analogues, pro-moieties (e.g., esters, amides), and conjugates used in drug discovery screening libraries.
  • The uracil chromophore provides UV detectability for in-process control (IPC) analytics during scale-up (HPLC at ~260–270 nm, literature), aiding impurity tracking and stability studies.

• Excipient status:

  • Not a common pharmacopeial excipient. If an excipient-like role (e.g., counterion, complexant) is contemplated, comprehensive safety/tox data and regulatory assessment would be required.

• Process chemistry considerations:

  • Salt screening (e.g., sodium, tromethamine) can improve solubility for processing or crystallization.
  • Formation of crystalline esters/amides may offer better handling properties (flowability, stability) for intermediates.
  • Control of residual DMF/NMP and coupling reagents (EDC urea, DCC urea byproducts) is critical; define purge strategies and analytical limits early.

All uses are for research and development only. No claims are made regarding efficacy, safety, or suitability for human or veterinary use.

Physical Properties

• Item-specific specifications (this lot):

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Grade/Purity: 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 (general reference; not item specifications):

  • Empirical formula (literature): C6H6N2O4
  • Formula weight (literature): ~170.12 g/mol
  • Physical state: typically a crystalline solid for analogous uracil-carboxylic acids.
  • Acid–base: one carboxylic acid (pKa1 often in the 2–4 range for aryl/heteroaryl acetic acids, literature), ring nitrogens can engage in H-bonding but are weakly basic.
  • Solubility profile: low to moderate in water (increases at basic pH via carboxylate formation); good in polar aprotic solvents (DMSO, DMF), and in aqueous buffers above the pKa due to deprotonation (literature/generic behavior).
  • LogP/logD: expected low to moderate hydrophilicity owing to three carbonyl oxygens (qualitative, literature-based).
  • Thermal transitions: many uracil-carboxylates exhibit high melting points with potential decomposition upon melting; verify for this item with CoA/SDS (literature trend).

• Optical/refractive: Not applicable/typical for solids; specific refractive index not usually reported.

Always consult the item-specific CoA for definitive values (mp, water content, residual solvents, metal analyses, and UV cutoff are Not specified for this item; refer to CoA/Spec Sheet).

Quality and Grades

• Item-specific status:

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

• Interpreting grades (general guidance):

  • Research grade: commonly used for synthesis and biochemical research; typical controls include identity (NMR/IR/HRMS), purity (HPLC/GC), and residual solvents/metals. If UV-transparent material is required (e.g., analytical HPLC), request HPLC-grade or a certificate specifying low UV background.
  • Biochemical grade: if available, implies tighter limits for bioburden/endotoxin and often specific water/metal limits; request documentation if working in enzyme assays or nucleic acid workflows sensitive to trace contaminants.

• What to check on the CoA for this compound class:

  • Identity confirmation: 1H/13C NMR consistent with uracil lactam resonances and carboxymethyl side-chain; melting point range; HRMS for [M±H].
  • Purity assay: HPLC (UV at 260–275 nm typical for uracil chromophore) with area % reported; residual solvents by GC.
  • Water content (Karl Fischer) for hygroscopicity assessment; most such acids are only mildly hygroscopic.
  • Residual inorganic impurities (metals) if intended for coupling chemistry where trace metals can catalyze degradation—request ICP if critical.

For any application demanding defined specifications (e.g., medicinal chemistry SAR, oligonucleotide conjugation), request the latest CoA and, if needed, a tailored specification. All unspecified values: Not specified for this item; refer to CoA/Spec Sheet.

Reaction and Applications

Uracil-4-acetic acid serves as a versatile building block that combines a nucleobase core with a carboxylic acid handle for conjugation and derivatization.

• Representative applications (literature/general):

  • Amide coupling: formation of amides with amines using EDC/HOBt, HATU/DIPEA, or CDI, enabling attachment of the uracil motif to linkers, peptides, or solid supports.
  • Esterification: Fischer esterification (ROH/H+), Steglich esterification (DCC/DMAP) to generate prodrug-like esters or handles for further chemistry.
  • Nucleobase functionalization: the uracil ring can undergo N-alkylation or selective halogenation at C-5 (via NIS/NBS on protected derivatives) after temporary protection or activation strategies.
  • Click-compatible linkers: convert the acid to azides/alkynes via amide/ester linkers to enable CuAAC or SPAAC installation of the uracil unit onto probes or materials.
  • Polymer/materials: immobilization on resins or surfaces through amide bonds to study base-pairing or to create hydrogen-bonding motifs in supramolecular polymers.

• Practical tips:

  • Control ionization: neutral (acid) form extracts well into organic solvents; as carboxylate it partitions into aqueous phases—adjust pH accordingly during workup.
  • Protecting groups: if further electrophilic substitution on the ring is planned, consider N-protection (e.g., benzyl or silyl on N1/N3) to direct reactivity and avoid over-alkylation.
  • Analytical: UV absorbance around 260–270 nm typical for uracil enables convenient HPLC monitoring of couplings and deprotections.

• Use in life-science research: as a uracil-tagged hapten/ligand or as a structural analogue in nucleotide-mimetic libraries (research use only).

Reaction Conditions

The following are general, literature-based conditions for transformations of uracil-derivative carboxylic acids and are not item-specific specifications.

• Amide coupling (to primary amines):

  • Solvent: DMF or DMF/DCM (anhydrous).
  • Reagents: HATU (1.1–1.5 equiv) or EDC·HCl (1.2–1.5 equiv) + HOAt/HOBt/NHS; base DIPEA (2–3 equiv).
  • Temperature/time: 20–25°C, 1–16 h; difficult substrates may require 40–50°C.
  • Workup: dilute with EtOAc, wash with 5% NaHCO3 then brine; or directly precipitate amide into water if insoluble.

• Steglich esterification (to alcohols):

  • Solvent: DCM or DCM/THF.
  • Reagents: DCC (1.1–1.3 equiv) + catalytic DMAP (0.05–0.2 equiv).
  • Temperature/time: 0°C to rt, 2–18 h.
  • Notes: remove dicyclohexylurea by filtration; avoid over-acylation of uracil nitrogens by keeping base catalytic only.

• NHS-ester formation (for bioconjugation):

  • Reagents: EDC (1.2–1.5 equiv) + NHS (1.2–1.5 equiv) in DMF or aqueous MES buffer (pH 5.5–6.0).
  • Couple immediately to amines at pH 7.5–8.5 to minimize hydrolysis.

• N-alkylation of uracil nitrogen (if unprotected):

  • Base: K2CO3 or Cs2CO3 in DMF; electrophile: alkyl bromide/iodide.
  • Temperature: 40–80°C; monitor to avoid dialkylation.

• Hydrogen-bond sensitive operations:

  • Avoid strong acids/bases at high temperature that can induce ring opening or decarboxylation.

Expected yields vary broadly (40–90%) depending on partners; monitor by HPLC at ~260–270 nm (uracil absorbance). Optimize equivalents and concentrations to minimize O→N acyl transfer on the uracil ring.

Safety and Handling

• Regulatory/GHS (item-specific):

  • Signal word: Not specified for this item; refer to SDS.
  • GHS classification: Not specified for this item; refer to SDS.
  • Hazard statements/pictograms: Not specified for this item; refer to SDS.

• General safety guidance for heteroaromatic carboxylic acids (literature/general):

  • Expected hazards: may cause skin and eye irritation; dust may cause respiratory tract irritation. Avoid breathing dust and avoid contact with eyes/skin.
  • PPE: laboratory coat, safety glasses with side shields, and appropriate chemical-resistant gloves (e.g., nitrile). Use a dust mask/respirator if airborne particulates could be generated.
  • Engineering controls: handle powders in a fume hood or ventilated enclosure; minimize dust formation. Use antistatic precautions when weighing dry powders.
  • First aid (overview; follow SDS/medical guidance):
    • 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; seek medical attention if irritation persists.
    • Ingestion: rinse mouth; do not induce vomiting unless directed; seek medical advice.
  • Incompatibilities: strong oxidizers and strong bases/acids that could cause decomposition or salt formation; carbodiimides (during coupling) may form reactive O-acylisourea intermediates—use standard coupling safety practices.
  • Thermal stability: avoid excessive heating; many uracil derivatives char/decompose before boiling.

Defer to the product SDS for authoritative hazard classification, exposure limits, spill response, disposal, and transport details.

Solvent Selection

Uracil-4-acetic acid is a polar, hydrogen-bonding capable heteroaromatic carboxylic acid. Solvent choice should balance dissolution of both the uracil ring system and the carboxylate functionality.

• Polarity/miscibility (general):

  • Highly soluble: DMSO, DMF, NMP.
  • Moderately soluble: methanol, ethanol, water at elevated pH (as the carboxylate salt), aqueous buffers above pH ~pKa.
  • Low solubility: nonpolar hydrocarbons and weakly polar ethers (unless used with base or co-solvent).

• Practical guidance:

  • For stock solutions: 10–100 mM stocks are readily prepared in dry DMSO; for aqueous systems, dissolve in a minimal volume of 0.1–0.5 M NaOH or Tris base, then dilute with buffer to target pH.
  • For coupling reactions: anhydrous DMF or DCM/DMF mixtures are typical with carbodiimide or uronium reagents; add base (DIPEA) as needed.
  • For crystallization/purification: water/MeOH, ethanol/water, or EtOAc/hexanes with an acid/base modulator (AcOH or NH3) can be tuned to control ionization state during crystallization.

• When to choose alternatives:

  • If greener profile desired, consider 2-MeTHF or CPME as co-solvents for workup/extractions when product is in organic phase post-esterification.
  • For bioconjugation in aqueous media, employ buffered saline at pH 7.4–8.5 with a water-miscible co-solvent (10–30% DMF or DMSO) to maintain solubility without denaturing biomolecules.

Note: exact solubility values for this item are Not specified; verify experimentally on your scale and temperature.

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.

• General storage guidance (solid):

  • Keep tightly closed in a dry, well-ventilated place. Protect from prolonged exposure to moisture and strong light. For long-term storage, consider desiccation (P2O5 or silica gel) to maintain consistent mass for analytical weighing.
  • If repeated access is expected, aliquot into smaller containers to minimize ambient humidity uptake.

• Reconstitution recommendations (general):

  • For organic stocks: dissolve in anhydrous DMSO or DMF to 10–100 mM; filter (0.22 μm) if required for cell-free biochemical assays. Record exact concentration gravimetrically.
  • For aqueous use: dissolve in minimal 0.1–0.5 M NaOH or Tris base to aid dissolution, then dilute into buffer; adjust pH to target. Avoid prolonged exposure of activated esters (e.g., NHS-ester derivatives) to moisture; prepare fresh.
  • Freeze–thaw: solid material is unaffected; for solutions, store aliquots at −20°C (DMSO/DMF) or 2–8°C (buffers) and avoid multiple freeze–thaw cycles to prevent hydrolysis and concentration drift.

All unspecified stability limits (shelf life, water content, UV cutoff, metals) are Not specified for this item; refer to CoA/Spec Sheet and SDS for authoritative guidance. Research use only.

Structure and Identity

Uracil-4-acetic acid is a uracil (pyrimidine-2,4-dione) derivative bearing a carboxymethyl substituent on the uracil ring framework, furnishing a bifunctional heteroaromatic acid useful as a nucleotide/nucleoside building block.

• Item-specific (from Product Data):

  • Product name: Uracil-4-acetic acid
  • CAS: 4628-39-1
  • PubChem CID: 73271
  • InChIKey (as provided): 245035
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/consensus identifiers and features (for reference; not item specifications):

  • Typical molecular formula: C6H6N2O4 (literature)
  • Typical molecular weight: ~170.12 g/mol (literature)
  • Core scaffold: pyrimidine-2,4-dione (uracil) ring.
  • Functional groups: two amide-like ring carbonyls (lactam carbonyls at C-2 and C-4 of uracil), one carboxylic acid (–CH2–CO2H) side chain.
  • Tautomerism: uracil ring supports lactam–lactim tautomerism; the lactam form predominates in the solid state and most polar solvents.

• 2D structural description (verbal):

  • A six-membered aromatic-like pyrimidine ring containing two ring nitrogens positioned 1,3 to each other, with carbonyls at the 2- and 4-positions (uracil). An acetic acid side chain (–CH2–CO2H) is attached to the uracil framework (uracil-4-acetic acid nomenclature reflects substitution on the uracil system), yielding a polar, hydrogen-bonding competent heteroaromatic carboxylic acid suitable for conjugation chemistry.

Note: Exact constitutional attachment pattern and electronic descriptors should be confirmed against the certificate of analysis (CoA) and authoritative databases for your lot.

Synthetic Utility

Uracil-4-acetic acid combines a heteroaromatic recognition element with a carboxylic acid functional handle, enabling a wide array of downstream transformations.

• Key reactive sites:

  • Carboxylic acid: amenable to activation (acid chlorides, anhydrides), amide coupling (HATU, EDC/NHS, PyBOP), esterification (Fischer, Steglich), and Curtius/Schmidt-type rearrangements via acyl azides (with due caution).
  • Uracil ring: electrophilic substitution at C-5 (after appropriate protection/activation) to introduce halogens or substituents; N-alkylation at N1/N3 under basic conditions with alkyl halides or sulfonates (regiochemistry controllable via protecting groups and base choice).

• Retrosynthetic value:

  • Serves as a convergent synthon to append uracil onto amine-bearing scaffolds (amide linkage) or alcohol-bearing scaffolds (ester/carbonate), preserving the nucleobase H-bonding face.
  • Precursor to clickable derivatives: conversion to NHS esters, acyl fluorides, or mixed anhydrides for rapid bioconjugation.

• Protecting group strategies:

  • Temporary protection of uracil NH (e.g., benzyl, silyl) can be advantageous to prevent undesired N-acylation or to direct ring functionalization. Acid-labile and hydrogenolysis-cleavable groups are commonly used.

• Purification and analytics:

  • Exploit acid/base switching to shuttle between aqueous and organic phases. HPLC with UV detection near 260–270 nm aids monitoring. NMR in DMSO-d6 or D2O (with base) cleanly resolves carboxymethyl and uracil resonances.

This balanced bifunctional scaffold is well-suited for constructing nucleobase-decorated libraries, surface ligands, and probe molecules.

Target Specificity

Not applicable. This product is a small-molecule uracil derivative, not a biological macromolecule or antibody. No antigen/epitope, species reactivity, clone, or isotype information applies. For biochemical interaction discussions, see Biological Roles and Reaction & Applications.