6-Butyl-2-thiouracil , CAS No.53939-84-7

CAS: 53939-84-7 Cat. No.: B970543 Formule: C₈H₁₂N₂OS Poids moléculaire: 184.26 PubChem CID: 11513878

Storage

Room temperature

Spécifications

Conditions de stockage de stockage

Room temperature

Noms et identifiants

Sourires canoniques

CCCCC1=CC(=O)NC(=S)N1

IUPAC Name

6-butyl-2-sulfanylidene-1H-pyrimidin-4-one

InChIKey

IDHIMFNQCHMJTF-UHFFFAOYSA-N

INCHI

1S/C8H12N2OS/c1-2-3-4-6-5-7(11)10-8(12)9-6/h5H,2-4H2,1H3,(H2,9,10,11,12)

Isomères SMILES

CCCCC1=CC(=O)NC(=S)N1

PubChem CID

11513878

Poids moléculaire

184.26

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: Pyrimidones
• Alternative Parents: Pyrimidinethiones 2-Thiopyrimidines Hydropyrimidines Vinylogous amides Heteroaromatic compounds Thioureas Lactams Azacyclic compounds Organopnictogen compounds Organooxygen compounds Organonitrogen compounds Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: 2-thiopyrimidine - Thiopyrimidine - Pyrimidone - Pyrimidinethione - Hydropyrimidine - Heteroaromatic compound - Vinylogous amide - Thiourea - Lactam - Azacycle - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organosulfur compound - Organooxygen compound - Organonitrogen compound - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as pyrimidones. These are compounds that contain a pyrimidine ring, which bears a ketone. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
• 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

Propriétés chimiques et physiques

• Poids moléculaire: 184.260 g/mol
• XLogP3: 1.300
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 3
• Exact Mass: 184.067 Da
• Monoisotopic Mass: 184.067 Da
• Topological Polar Surface Area: 73.200 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 235.000
• 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 manufacturer-verified application protocols are provided for this item.

General research-use guidance (non-validated; optimize in-house):

• Stock solution preparation: dissolve in anhydrous DMSO (e.g., 10–100 mM), filter (0.22 µm PTFE) if required, store aliquots under inert gas at −20 to 4 °C protected from light; check stability by LC–MS before critical assays.
• Biochemical assays: dilute DMSO stocks into assay buffer to ≤1–2% v/v DMSO final; include vehicle controls. Avoid oxidizing components that might modify the thione.
• Synthetic use: for S- or N-alkylation, see the Reaction Conditions tab for starting points; monitor by LC–MS/1H NMR to resolve S- vs N-alkylation products.

Note: These are general literature-based suggestions and are not product-specific validated protocols.

Biological Roles

General/literature context (not item-specific claims):

• Nucleobase analogue: 2-thiouracil is the thio-analogue of uracil. Sulfur substitution at C2 alters hydrogen-bonding and photophysics compared with uracil. The 6-butyl group increases hydrophobicity, influencing base-stacking and membrane association in model systems.
• Tautomerism and recognition: thione–thiol and lactam–lactim equilibria modulate donor/acceptor patterns at ring nitrogens and heteroatoms, affecting pairing with complementary bases and enzyme recognition (e.g., nucleoside phosphorylases, polymerases—literature observations with thio-nucleobases in general).
• Sulfur in biology: 2-thiouridine modifications occur naturally in tRNA and modulate decoding/thermal stability (literature); while 6-alkyl substitution is not a natural modification, such analogues are used to probe structure–function relationships.
• Enzyme interaction studies: thiouracil scaffolds are widely used in fundamental research on peroxidases and deiodinase-related processes due to their sulfur functionality; any findings are for research understanding only (no clinical/therapeutic claims).

Use guidance:

• Treat this compound strictly as a research tool. If using in biochemical assays, prepare fresh stock solutions (e.g., in DMSO) and verify absence of oxidation products by LC–MS where results are sensitive to redox state.

Buffer Applications

This compound is not a buffering agent and is not typically used to prepare biological buffers. If used in biochemical assays, it is generally dissolved in a suitable co-solvent (e.g., DMSO) and then diluted into the assay buffer.

Practical guidance (general):

• Stock preparation: prepare concentrated stocks in DMSO or DMF; final assay co-solvent level typically kept ≤1–2% v/v to minimize interference (optimize per assay).
• pH effects: solubility may improve in basic buffers due to deprotonation, but verify assay compatibility; avoid strong oxidizing buffer components that could modify the thione.

Green Alternatives

Context: 6-Butyl-2-thiouracil is a solid heterocycle; “greener alternatives” primarily concern solvent and reagent choices during its use, not substitution of the molecule itself in studies requiring this exact scaffold.

Greener solvent strategies (literature/guidance):

• Dissolution/reactions:
  • Prefer EtOAc, 2-MeTHF, or propylene carbonate over DMF/DMSO when feasible (solubility permitting).
  • For S-alkylation, MeCN or 2-MeTHF with K2CO3/Cs2CO3 can reduce EHS burdens vs DMF.
• Work-up and purification:
  • Use ethanol or isopropanol for crystallization instead of chlorinated solvents.
  • Replace dichloromethane with EtOAc/heptane systems where chromatographic resolution allows.

Reagent choices and energy:

• Halogenation at C5: NBS/NCS in safer solvents (EtOAc, MeCN) instead of bromine/chlorine in chlorinated media.
• Bases: carbonate bases (K2CO3) reduce hazards compared to NaH/t-BuOK where S-alkylation selectivity suffices.
• Energy: conduct reactions at ambient temperature with phase-transfer catalysts (e.g., TBAB) when possible to cut heating time.

Trade-offs:

• DMF/DMSO deliver superior solubility and rates but complicate removal and pose EHS concerns.
• Greener ethers (2-MeTHF) may limit solubility; process intensification (ultrasound, higher dilution, or slight warming) may be needed.

Summary table (general):

• DMF vs MeCN: DMF = higher solubility/rate; MeCN = easier work-up, lower EHS impact.
• DCM vs EtOAc: DCM = strong eluent, higher hazard; EtOAc = biodegradable, safer.
• NaH vs K2CO3: NaH = strong, N-alkylation; K2CO3 = milder, favors S-alkylation.

Pharmaceutical Uses

Item-specific regulatory/excipient status: Not specified for this item; refer to CoA/Spec Sheet. Supplied strictly for research use only (per Product Data: Research Use Note).

General context (non-clinical):

• Process and analytical research: thiouracil analogues can serve as reference standards, impurity markers, or synthetic intermediates in medicinal chemistry programs exploring nucleobase-derived scaffolds. 6-Butyl substitution modulates lipophilicity for SAR exploration.
• Formulation research: when used as a model heteroaromatic in preformulation, typical vehicles include DMSO, PEG 400, or mixed co-solvent systems to achieve workable concentrations for in vitro assays. No implication of therapeutic use is intended.

Compliance note: This product is not intended for human or veterinary use, diagnostic procedures, or clinical applications. For any regulated development work, establish your own specifications and qualify the material per your quality system.

Physical Properties

Item-specific properties from Product Data:

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

Literature/class properties for 6-alkyl-2-thiouracils (context only; not item specifications):

• Aggregated molecular properties (literature/computed):
  • Molecular weight: ~184.26 g/mol (for C8H12N2OS).
  • Hydrogen-bond donors/acceptors: 1–2 donors (tautomer dependent), 2 acceptors (C=O, C=S) (literature).
  • Polar surface area: moderate due to C=O/C=S and ring nitrogens (literature trends for thiouracils).
• Phase/thermal behavior (literature): typically crystalline solids with melting points in the 150–220 °C range across 6-alkyl homologs; specific MP for 6-butyl-2-thiouracil not cited here.
• Solubility (literature, qualitative):
  • Water: low to very low at ambient temperature (increasing with pH via deprotonation at N3).
  • Organic: soluble in polar aprotic solvents (DMSO, DMF, NMP); sparing to moderate in alcohols; low in nonpolar hydrocarbons despite the butyl group due to heteroatoms.
• LogP/logD (literature expectation): higher lipophilicity than 2-thiouracil due to the butyl substituent; exact values not cited.
• UV characteristics (literature): conjugated pyrimidinone-thione chromophore absorbs in near-UV; exact λmax not cited here.

Note: Where exact numerical values are required for your method development, please consult the item’s CoA/Spec Sheet or generate in-house measurements.

Quality and Grades

Item-specific quality information from Product Data:

• 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 (general information for planning):

• Research grade heterocycles are commonly supplied at ≥95% purity by HPLC/GC/NMR. For structure–activity studies or analytical calibrants, higher assay (≥98%) and tighter controls on residual solvents/metals are often preferred. Verify the exact assay on the provided CoA.
• HPLC grade designation (if present on a specific pack) indicates low UV-absorbing impurities suited for analytical work; it does not imply suitability for clinical/therapeutic use.
• Stabilizers: 6-Butyl-2-thiouracil typically does not require added stabilizers. If present, stabilizers will be declared on the label/CoA; consider their impact on downstream reactions (e.g., potential interference in S-alkylation or metal catalysis).
• Trace specifications: If your application is catalyst-sensitive (e.g., C–H functionalization, metal-catalyzed cross-coupling on the ring), request metal ion content and water content data. Otherwise, standard research-grade specifications are typically adequate.

Recommendation: Use the exact batch CoA for method validation and regulatory documentation; do not extrapolate from literature values to item specifications.

Reaction and Applications

Research applications (general/literature; expand beyond catalog):

• Nucleobase analogue chemistry: 6-alkyl-2-thiouracils serve as surrogates of uracil with a thioxo at C2 and hydrophobic C6 substitution, useful in probing stacking/H-bonding effects in nucleobase recognition and materials.
• Derivatization handles:
  • S-alkylation at C2 thione to access 2-alkylthio uracils (thioethers), often key intermediates toward nucleoside analogues or sulfur-modified ligands.
  • N-alkylation at N1/N3 to tune basicity and solubility; quaternization possible with powerful electrophiles.
  • Electrophilic substitution at C5 (e.g., bromination/chlorination) enabling further cross-coupling or lithiation–trapping sequences.
• Coordination chemistry: thione/thioamide sulfur can bind soft metals (Cu+, Ag+, Au+), enabling metal–organic frameworks or sensing motifs (literature). The butyl substituent provides hydrophobic anchoring in amphiphilic assemblies.
• Materials/photochemistry: thiouracil chromophores show distinctive n→π* transitions; heavy-atom-free intersystem crossing enhancements have been reported for thio-nucleobases (literature), supporting photophysical studies.

Practical tips (general):

• Drying: brief drying under vacuum at ambient to 40 °C removes residual moisture/solvents without risking decomposition; avoid high temperatures.
• Base choice steers selectivity: mild carbonate promotes S-alkylation; strong bases favor N-alkylation—monitor by LC–MS/NMR.
• Protect from strong oxidants: the thione can oxidize; perform oxidant-sensitive steps under inert atmosphere when needed.
• Purification: product mixtures often resolve well by recrystallization from alcohols or by normal-phase silica with polar eluent modifiers (e.g., 1–2% MeOH in DCM or EtOAc/hexanes).

Reaction Conditions

General literature conditions for common transformations of 2-thiouracil scaffolds (guidance only; optimize per substrate):

• S-Alkylation at C2 (forming 2-thioethers):
  • Typical: K2CO3 or Cs2CO3 (1.5–2.0 equiv) in DMF or MeCN, 0.05–0.2 M, rt to 60 °C, 2–12 h; electrophile = primary alkyl or benzyl bromide/iodide. Often selective for sulfur under these mild conditions. Isolated yields commonly 60–90% (literature range).
• N-Alkylation (N1/N3):
  • Conditions: NaH (60% oil, 1.1–1.5 equiv) in dry THF or DMF, 0 °C to rt, 1–6 h; add alkyl halide slowly. Stronger bases (t-BuOK) and higher temperatures can shift regioselectivity. Mixtures of N1/N3 isomers are common; chromatographic or crystallization separation recommended.
• Electrophilic halogenation at C5:
  • NBS or NCS (1.05–1.2 equiv) in DMF, MeCN, or AcOH at 0–25 °C, 0.1–0.3 M, 0.5–3 h; monitor by TLC/HPLC. Subsequent cross-coupling requires suitable activation and catalyst.
• Directed metalation at C5 (for further elaboration):
  • LDA or s-BuLi at −78 to −40 °C in THF, then trap with electrophiles (CO2, aldehydes, halogens). Protecting groups or temporary metal coordination can improve selectivity (literature advanced practice).
• Oxidation state adjustments:
  • Controlled oxidation of the thione to sulfenyl/sulfinyl/sulfonyl derivatives is possible with mCPBA or oxone at low temperatures; conditions must be tuned to avoid overoxidation and ring degradation.

Work-up tips:

• Quench bases carefully (ice-cooled MeOH/H2O) and neutralize to avoid ring hydrolysis.
• Remove high-boiling solvents (DMF/DMSO) via aqueous work-up and solvent exchange; employ antisolvent crystallization (EtOH/H2O) when feasible.

All conditions above are literature guidance and not specifications for this catalog item.

Safety and Handling

Item-specific hazard data from Product Data:

• GHS classification, signal word, pictograms, H-statements: Not specified for this item; refer to SDS.

General safety considerations for thiouracil derivatives (literature/good laboratory practice):

• Likely hazards: may cause irritation to eyes, skin, and respiratory tract as a fine organic powder. Avoid dust formation and inhalation.
• Endocrine/biochemical activity: thiouracil scaffolds are known to interact with thyroid-related enzymes in biological systems (literature). Handle strictly as a research chemical; avoid exposure and ingestion. No medical/clinical use.
• PPE: wear lab coat, safety glasses, and appropriate disposable gloves (e.g., nitrile). Handle in a fume hood, especially during weighing and when using volatile solvents or bases for derivatization.
• Incompatibilities (general): strong oxidizers (risk of exotherm/oxidation of thione), strong acids/bases (can induce decomposition or undesired alkylation/cleavage), and halogenating agents (electrophilic substitution at C5 possible). Keep away from ignition sources when using organic solvents.
• First aid (overview; defer to SDS):
  • Inhalation: move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: rinse with water for several minutes; remove contaminated clothing; seek medical attention for persistent irritation.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical attention.
• Waste: collect solid residues and contaminated consumables as halogen-free organic waste unless process chemistry introduces halogens/heavy metals; dispose per institutional/EHS guidance.

Always consult the product-specific SDS for authoritative hazard, toxicological, and first-aid information.

Solvent Selection

Applicability: As a moderately polar heteroaromatic solid, 6-butyl-2-thiouracil dissolves best in polar aprotic media; selection depends on transformation (S- vs N-alkylation, electrophilic substitution) and work-up constraints.

• Polarity and miscibility (literature/general):
  • Preferred solvents for dissolution: DMSO, DMF, NMP. Warm ethanol or isopropanol can also dissolve at moderate concentrations. Solubility in water is poor at neutral pH but improves at basic pH via deprotonation.
  • Poor solvents: alkanes and nonpolar aromatics (hexane, toluene) unless used as anti-solvents for crystallization.
• Choosing a solvent by task:
  • S-alkylation at C2 (to form 2-alkylthio derivatives): DMF or MeCN with mild base (K2CO3, Cs2CO3) balance rate and selectivity.
  • N-alkylation (N1/N3): stronger bases (NaH, t-BuOK) in THF/DMF; solvent controls regioselectivity alongside base and temperature.
  • Electrophilic halogenation at C5: DMF, acetonitrile, or acetic acid commonly used with NBS/NCS.
  • Crystallization and purification: alcohols or alcohol/ether mixtures can assist in selective precipitation; water addition to DMSO/DMF solutions can induce crystallization.
• Small comparison (literature guidance):
  • DMSO: highest solvating power; difficult removal; compatible with many bases.
  • DMF: excellent balance of solubility and work-up; consider amide safety policies.
  • MeCN: cleaner work-up; may require longer reaction times due to lower solubility.
  • 2-MeTHF/EtOAc: greener options for work-up and crystallization rather than for initial dissolution.

Note: Verify actual solubility of your batch empirically; consult the CoA if available.

Storage and Reconstitution

Item-specific storage from Product Data:

• Storage conditions: Room temperature.
• 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 (good practice for heteroaromatic thiocarbonyls):

• Protection: Store tightly closed in a desiccator or with a desiccant pack to limit moisture uptake. Protect from prolonged light exposure to minimize potential photochemical changes in the thione chromophore.
• Atmosphere: For long-term storage after opening, consider an inert headspace (argon/nitrogen), especially if frequent opening/closing is expected.
• Reconstitution:
  • For analytical/biological studies: prepare concentrated stocks in anhydrous DMSO or DMF; vortex/sonicate gently to aid dissolution. Filter through PTFE syringe filters if particulate is present.
  • For synthetic use: dry the solid under vacuum at ambient–40 °C before use to remove adsorbed moisture/solvent traces.
• Freeze–thaw: Not typically applicable to solids. For DMSO/DMF stock solutions, aliquot to avoid repeated freeze–thaw; store at −20 °C protected from light and air.

Always refer to the product label and batch CoA for any additional, item-specific handling instructions.

Structure and Identity

Brief: 6-Butyl-2-thiouracil is a sulfur-substituted uracil (pyrimidine-2-thione-4-one) bearing a linear butyl group at C6; a thio-analogue of uracil commonly used as a heteroaromatic building block in nucleobase chemistry.

• Item-specific identifiers (from Product Data):
  • SKU: B970543
  • Product name: 6-Butyl-2-thiouracil
  • CAS: 53939-84-7
  • PubChem CID: 11513878
  • InChIKey: 137967 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Literature/structural description (general):
  • Core scaffold: pyrimidine ring with carbonyl at C4 and thioxo (C=S) at C2; N1 and N3 are ring nitrogens capable of tautomerism and H-bonding.
  • Substitution pattern: n-butyl group at C6 (sp2 carbon of the pyrimidine ring), increasing hydrophobicity vs 2-thiouracil.
  • Functional groups: thioamide-like C=S (thione), lactam C=O (uracil 4-one), two ring nitrogens (one typically NH depending on tautomer), and a linear alkyl chain (CH3–CH2–CH2–CH2–).
  • Tautomerism: thione–thiol and lactam–lactim equilibria possible (literature), with thione/lactam generally dominant in polar media.
• Literature molecular formula and mass (for context; not item-specific):
  • Formula (literature): C8H12N2OS
  • Molecular weight (literature): ~184.26 g/mol
• 2D description in words: a six-membered diazine ring bearing a carbonyl at position 4 and a thioxo at position 2; the carbon at position 6 carries a straight-chain butyl substituent; one ring nitrogen is protonated in the predominant neutral tautomer.

Synthetic Utility

Role as a building block (literature/general):

• Bifunctional heterocycle: combines a thione (C=S) and a pyrimidinone (C=O) enabling orthogonal transformations.
• Electrophile at C2 vs nucleophile at N sites: allows selective S-alkylation at the thione (soft nucleophile) under mild basic conditions, and N-alkylation at N1/N3 under stronger basicity.
• C5 functionalization platform: electrophilic halogenation (NBS/NCS) or lithiation at C5 (via directed metalation) to install handles (e.g., bromo/chloro) for cross-coupling, enabling diversification at the 5-position orthogonal to the existing C6-butyl.

Representative transformations (literature):

• S-Alkylation: 6-butyl-2-thiouracil + R–X (R = benzyl, alkyl) with K2CO3/Cs2CO3 in DMF/MeCN → 2-(thioether) derivatives.
• N-Alkylation: NaH (THF/DMF) with alkyl halides → N1- or N3-alkylated isomers; regioselectivity influenced by base, solvent, and temperature; separable by chromatography.
• Halogenation: NBS/NCS (DMF/AcOH) → 5-halo intermediates, competent partners in Suzuki/Miyaura or Buchwald–Hartwig chemistry after further activation.
• Metal coordination/derivatization: formation of thione–metal complexes (Ag, Cu) used in materials and sensing studies.

Retrosynthetic note: The 6-butyl substituent can be introduced via alkylation of a 6-halo-2-thiouracil or through cyclization strategies from appropriately substituted β-dicarbonyl/thiourea precursors. The presence of the butyl group increases lipophilicity and can aid crystallization and chromatographic separation.

Target Specificity

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

Item-specific data: Not specified for this item; refer to CoA/Spec Sheet if any bioassay characterizations are provided for research context.