6-Methoxymethyl-2-thiouracil - Reagent grade

Cat. No.: M482919

GRADE & PURITY Reagent Grade

Storage

Room temperature

Specifications

Specifiche e purezza

Reagent grade

Condizioni di conservazione di stoccaggio

Room temperature

Grado

Reagent Grade

Application Protocols

No assay-specific protocols are validated or provided in the Product Data for this item.

General laboratory usage suggestions (research context):

• Stock solution preparation: Dissolve in anhydrous DMSO or DMF to prepare a concentrated stock (e.g., 10–100 mM), then dilute into the reaction or assay medium immediately before use to avoid precipitation
• Nucleoside coupling: Follow standard Vorbrüggen protocols after silylation; rigorously exclude water and use freshly dried solvents
• S-alkylation screens: Combine substrate with base (e.g., K2CO3) in DMF or MeCN; add electrophile dropwise at 0–25°C; monitor by LC–MS

For method-critical work, develop and validate internal SOPs. Always consult primary literature for detailed, reaction-specific protocols.

Biological Roles

This product is intended strictly for research use in chemical/biochemical laboratories. No clinical or diagnostic use is intended or implied.

• Context (general literature):

  • Uracil is a canonical RNA nucleobase. 2-Thiouracil (s2U) is a naturally occurring modified nucleobase found in certain tRNAs, where sulfur at C2 modulates codon–anticodon interactions and thermodynamic stability.
  • Substitution at C6, as in 6-methoxymethyl-2-thiouracil, is not a natural RNA nucleobase but represents a synthetic analog useful for probing structure–function relationships and for installing handles for further derivatization.

• Biochemical properties of 2-thiouracil derivatives (literature):

  • Increased polarizability at C=S enhances stacking and H-bonding patterns relative to C=O analogs, potentially affecting duplex stability in nucleoside/nucleotide derivatives
  • The thione can participate in metal coordination or be selectively alkylated, enabling bioconjugation strategies post-glycosylation

• Applications in research:

  • Synthesis of modified nucleosides/nucleotides for enzymology and RNA structure studies
  • Photophysical probes or crosslinking handles upon further modification at sulfur or C6 substituent

Any biological discussion here is general background on nucleobase analogs. Verify compatibility and toxicity in your specific biological system before use; adhere to institutional safety protocols.

Buffer Applications

This compound is not a buffering agent and is not commonly employed to prepare pH buffer systems. It lacks a conjugate acid/base pair with a suitable concentration-independent pKa window for routine buffering.

• Practical note: If used in biochemical assays, select an appropriate buffer (e.g., phosphate, HEPES, MOPS) based on your target pH and ionic strength. Assess the compound’s solubility and stability in the chosen buffer; cosolvents (e.g., ≤1–5% DMSO) may be required to dissolve this heterocycle.

Refer to the Solvent Selection and Storage & Reconstitution sections for dissolution guidance.

Green Alternatives

Greener practice considerations focus on solvent and reagent choices; the heteroaromatic scaffold itself is fixed by design.

• Solvent substitutions (literature-informed):

  • Replace DMF/DMSO (difficult to remove, EHS concerns) with:
    • Dimethyl carbonate (DMC) or propylene carbonate for some SN2 S-alkylations
    • MeTHF or CPME for non-polar steps after silylation (enhanced safety vs DCM/DCE)
    • Acetonitrile remains a balanced choice for Lewis-acid-promoted glycosylations; consider ethanol or ethyl acetate where compatible

• Workup and purification:

  • Favor aqueous ethanol or isopropanol crystallizations instead of extensive silica chromatography when possible
  • Employ minimal solvent volumes; recover and recycle MeCN/EtOAc using in-house distillation where permitted

• Reagent choices:

  • Use catalytic silylation protocols (e.g., HMDS with catalytic ammonium salts) to reduce reagent load
  • Consider solid-supported acids (e.g., silica–TfOH) to simplify quench and reduce solvent use

• Trade-offs (balanced view):

  • MeTHF/CPME provide improved safety and life-cycle metrics but may reduce solubility of unsilylated substrates, requiring higher temperature or longer reaction times
  • Carbonate solvents are greener but may be incompatible with strong Lewis acids or moisture-sensitive steps

Small comparison (general):

• Traditional: DMF, DMSO, DCM, DCE — high solvency/compatibility; EHS and disposal burdens
• Greener: MeTHF, CPME, EtOAc, alcohols, carbonates — improved EHS; verify solubility and reactivity before scale-up.

Pharmaceutical Uses

No pharmacopeial or excipient status is provided in the Product Data for this item, and it is sold for research use only.

• General research/manufacturing context (non-clinical):

  • Can serve as a synthetic intermediate in the preparation of modified nucleosides/nucleotides for SAR studies during preclinical discovery chemistry
  • Potential utility as a building block in library synthesis targeting nucleobase-mimetic scaffolds

• Formulation considerations for research materials (general):

  • For in vitro assays, stock solutions are typically prepared in DMSO due to solubility; dilute into assay buffer immediately before use to minimize precipitation
  • For solid formulations (reference materials), protect from moisture and ambient light as needed; verify polymorph/solvate state if analytical consistency is required

No therapeutic claims are made. This material is not intended for human or veterinary use.

Physical Properties

Item-specific physicochemical specifications (mp, bp, UV cutoff, residue-on-ignition, trace metals, water/peroxide content) are not provided in the Product Data for this SKU.

• Provided for this item:

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet. (See computed value under Structure & Identity.)

• Literature/computed general properties for 2-thiouracil derivatives (for guidance only; not item specifications):

  • Physical state: typically crystalline solids for small thiouracil derivatives
  • Thermal behavior: many substituted thiouracils melt/decompose rather than show a clean boiling transition under ambient pressure
  • Hydrogen-bonding: capable of both H-bond donation (ring NH) and acceptance (C=O, C=S), often leading to limited aqueous solubility
  • Solubility profile (qualitative, literature):
    • Water: sparingly soluble to slightly soluble
    • Alcohols: low to moderate solubility depending on substitution
    • Polar aprotic solvents (DMSO, DMF, NMP): good solubility typical for nucleobase analogs
    • Chlorinated solvents (DCM, DCE): variable; often improved upon silylation
  • Acid–base behavior: ring nitrogens are weakly basic; deprotonation at N1 or thione–thiol tautomerization can occur under strong base

• Refractive index, logP, pKa: Not specified for this item; consult primary literature or perform measurement as required for your application.

Always verify exact specifications for your lot on the CoA; do not rely on generalized literature values for method-critical work.

Quality and Grades

• Item-specific quality:

  • Grade/Purity: Reagent Grade (as provided). No additional assay or impurity specifications are listed in the Product Data.

• What “Reagent Grade” typically signifies (general guidance):

  • Suitable for general laboratory synthesis and preparative work
  • Not certified for chromatographic baselines (unlike HPLC/LC–MS grades) and not intended for clinical or GMP use
  • UV background, trace metals, water/peroxide content, and stabilizers are not controlled to ultra-low levels unless explicitly specified

• Implications for use:

  • For method development in analytical contexts (HPLC/UV), evaluate baseline and potential impurities before use
  • For sensitive organometallic or anhydrous reactions, consider drying and/or recrystallization if your process demands tighter specs; verify residual moisture or impurities experimentally

• Confirmation recommended:

  • If you require defined parameters (e.g., residual solvent content, ash, trace metals), obtain the lot-specific CoA/Specification Sheet. Where exact numbers are absent: “Not specified for this item; refer to CoA/Spec Sheet.”

• Stabilizers and additives:

  • None are stated in the Product Data. If stabilizers are present, they will appear on the CoA/SDS for your lot.

Reaction and Applications

As a 2-thiouracil bearing a benzylic-like 6-methoxymethyl group, this scaffold serves as a versatile building block in nucleoside and nucleobase chemistry.

• Representative application families (literature):

  • Nucleoside synthesis: After N/O-silylation (e.g., HMDS + catalytic TMSCl or imidazole), Vorbrüggen-type glycosylation with protected sugar acetates/halides under Lewis acid activation (TMSOTf, SnCl4) to afford 2-thiouridine analogs
  • S-alkylation/acylation: The thione is nucleophilic; SN2 reactions with alkyl halides or Michael acceptors furnish thioethers or thioesters, enabling late-stage diversification
  • Oxidation/desulfurization: Controlled oxidation (e.g., H2O2, mCPBA) can deliver uracil analogs (desulfurized) or sulfenyl/sulfinyl/sulfonyl derivatives depending on conditions
  • Metal-catalyzed cross-coupling surrogates: After installation of suitable handles (e.g., S-arylation), subsequent functionalization on the 6-substituent can elaborate libraries
  • Protecting-group strategies: The methoxymethyl at C6 can be leveraged as a latent alcohol equivalent; acidic conditions can unmask a cationic intermediate enabling further substitution at C6 (method-dependent)

• Practical tips:

  • Pre-dry and silylate the nucleobase to enhance N1 nucleophilicity and solubility before glycosylation
  • Control chemoselectivity between S- and N-alkylation by base choice, solvent, and temperature (softer bases and polar aprotic solvents favor S-alkylation)
  • Monitor tautomeric state; additives (e.g., silylating agents) shift equilibria beneficially for coupling
  • For oxidative steps, add oxidant slowly at low temperature to minimize over-oxidation and ring degradation

These literature-guided uses should be adapted to your specific substrate protection scheme and desired regiochemistry.

Reaction Conditions

Representative literature-guided conditions (general guidance; optimize for your substrate and scale):

• Pre-activation (silylation) for glycosylation:

  • Reagents: HMDS (hexamethyldisilazane) with catalytic TMSCl or ammonium sulfate; or BSA (N,O-bis(trimethylsilyl)acetamide)
  • Solvent: dry MeCN or toluene; 60–120°C (reflux) until homogeneous
  • Workup: remove volatiles under reduced pressure; co-evaporate with dry solvent prior to coupling

• Vorbrüggen-type N1-glycosylation:

  • Glycosyl donor: per-acetylated ribose or protected sugar halide
  • Promoter: TMSOTf (0.5–1.5 equiv) or SnCl4/BF3·Et2O
  • Solvent: dry MeCN or DCE; temperature −20°C to room temp
  • Typical times: 0.5–6 h; monitor by TLC/LC–MS
  • Notes: Control moisture rigorously; β/α selectivity depends on donor, solvent, and temperature

• S-alkylation (to form thioethers):

  • Base: K2CO3, Cs2CO3, or NaH (for more reactive electrophiles)
  • Electrophiles: primary alkyl bromides/iodides, benzyl halides, Michael acceptors
  • Solvent: DMF, MeCN, or acetone; 0–25°C (SN2) to 50°C as needed
  • Tips: Softer conditions favor S over N alkylation; add electrophile slowly

• Oxidation/desulfurization:

  • Oxidants: H2O2 (acetic acid or MeOH), mCPBA (DCM), Oxone (aqueous–organic)
  • Temperature: 0–25°C to limit over-oxidation; monitor closely

• Purification:

  • Reverse-phase or normal-phase chromatography; or crystallization from alcohol/EtOAc depending on product polarity.

These are literature-style starting points; perform small-scale trials and adjust equivalents/temperature accordingly.

Safety and Handling

GHS classification, signal word, pictograms, and H-statements are not provided in the Product Data for this item. Always consult the product SDS for authoritative safety information before use.

General laboratory safety considerations for heteroaromatic thiocarbonyl compounds (literature/guidance):

• Likely hazards: May cause irritation to skin, eyes, and respiratory tract. Dust may be irritating. Avoid inhalation and contact.
• Personal protective equipment (PPE):
  • Safety glasses or chemical splash goggles
  • Lab coat
  • Nitrile gloves (change regularly); consider double-gloving for extended handling
  • Work in a fume hood to control dust and vapors from reagents/solvents used with the compound
• Handling practices:
  • Minimize dust generation; use disposable weigh boats and antistatic measures
  • Avoid strong oxidizing agents; thioamides can be susceptible to oxidation
  • For moisture-sensitive transformations (e.g., silylation, glycosylation), handle under dry inert atmosphere
• First-aid (overview; follow SDS):
  • 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
  • Inhalation: Move to fresh air; seek medical attention if symptoms develop
  • Ingestion: Rinse mouth; seek medical attention
• Fire response: Use CO2, dry chemical, or foam depending on surrounding materials. Combustion may produce NOx, SOx.

Defer to the SDS for detailed hazard, toxicological, and ecological information specific to this product.

Solvent Selection

6-Methoxymethyl-2-thiouracil is a polar, heteroatom-rich nucleobase analog. Practical solvent selection centers on achieving adequate solubility while preserving chemoselectivity at the thione and ring nitrogens.

• Polarity & interactions (general literature):

  • Capable of multiple H-bonding interactions (donor/acceptor), favoring polar aprotic solvents for dissolution
  • Silylation markedly increases solubility in low-polarity media (useful for glycosylations)

• Recommended solvent choices by task:

  • Stock solutions, screening: DMSO or DMF (good solubility at room temperature); NMP is an alternative
  • Nucleoside glycosylation (Vorbrüggen-type): dry MeCN or DCE after pre-silylation in HMDS/imidazole; promoters such as TMSOTf
  • S-alkylation/S-arylation: DMF, MeCN, acetone, or MeOH with appropriate base; polar solvents facilitate SN2 processes at sulfur
  • Oxidations/desulfurizations: Acetic acid, MeOH, or aqueous-organic media depending on oxidant (verify compatibility)

• Comparison (general guidance):

  • DMSO: maximal solubility; high bp complicates workup
  • DMF: good solvency; may need rigorous drying; challenging to remove
  • MeCN: compatible with Lewis-acid catalysis; moderate solubility unless silylated
  • DCE/DCM: useful after silylation; low polarity may limit raw substrate solubility

Always verify solubility empirically with your lot and planned conditions. For moisture-sensitive steps, ensure anhydrous grade solvents and inert atmosphere.

Storage and Reconstitution

• Storage conditions (from Product Data):

  • Store at room temperature.
  • Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

• Stability considerations (general guidance for thiouracils):

  • Protect from prolonged exposure to strong light and oxidants; store in a tightly closed container with desiccant if possible
  • If repeated handling is expected, consider aliquoting to minimize moisture exposure

• Reconstitution/dissolution (general guidance):

  • Prepare stock solutions in anhydrous DMSO or DMF. Typical laboratory stocks: 10–100 mM depending on solubility and intended use
  • For aqueous applications, first dissolve in a small volume of DMSO, then dilute into buffer with vigorous mixing; final DMSO content is often kept ≤1–5% v/v to limit precipitation
  • Filter sterilization (0.22 µm) may be used for biological assays if compatible; assess adsorption losses on membranes

• Freeze–thaw:

  • If storing solutions, keep at −20°C to −80°C in tightly sealed vials; minimize freeze–thaw cycles by aliquoting
  • Inspect for precipitation or discoloration upon thawing; re-warm gently and sonicate if needed

Always refer to the lot-specific CoA/SDS for definitive storage and handling guidance. Research Use Only: For research use only.

Structure and Identity

A substituted pyrimidine-2-thione (thiouracil) bearing a methoxymethyl substituent at the 6-position; a sulfur replaces the C2 carbonyl oxygen of uracil, and the ring is 1,3-diazine.

• Item-specific identifiers from Product Data:

  • CAS: Not specified for this item; refer to CoA/Spec Sheet.
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Computed/literature identity (for reference; not item specifications):

  • Core scaffold: pyrimidine ring with two endocyclic nitrogens at positions 1 and 3
  • Functional groups: 2-thioxo (C=S) carbonyl surrogate, 4-keto (C=O), 6-(methoxymethyl) substituent (-CH2–O–CH3)
  • Tautomerism: 2-thiouracils exhibit thione–thiol tautomerism; the thione form (C=S) is typically dominant in polar media (literature)
  • Approximate molecular formula: C6H8N2O2S (computed from structure; literature)
  • Approximate molecular weight: ~172.21 g/mol (literature/computed)

• 2D structural description (literature):

  • A six-membered 1,3-diazine ring with carbonyl at C4 and thioxo at C2; N1 and N3 are ring nitrogens capable of hydrogen bonding. The 6-position (para to N1, ortho to N3) bears a –CH2–O–CH3 substituent. The ring typically exists as a planar conjugated system enabling keto–thioamide resonance.

Note: Exact registry identifiers (CAS, InChI, SMILES) are not provided in the Product Data and should be confirmed on the product CoA or specification sheet before use in regulated documentation.

Synthetic Utility

Functional group arrangement confers multiple, orthogonal handles:

• Thione at C2 (C=S):

  • Nucleophilic sulfur enables S-alkylation/acylation to give thioethers/thioesters (literature)
  • Oxidation/desulfurization to the corresponding uracil under controlled conditions (e.g., H2O2, mCPBA, or Raney Ni; literature)
  • Transient metal coordination can activate for subsequent transformations

• Ring nitrogens (N1, N3):

  • After silylation (HMDS, BSA), N1 becomes the principal nucleophile for glycosylation under Vorbrüggen conditions to furnish β-configured nucleosides from acetylated sugars (literature trend)
  • Alkylation selectivity between N1/N3 can be tuned by base, solvent, and temperature

• C6–CH2–OMe substituent:

  • Acts as a benzylic-like methoxymethyl handle; under acidic activation it can be displaced or transformed into other substituents
  • Oxidation to the corresponding aldehyde or alcohol (via demethylation/hydroxymethylation strategies) provides entry to diversified C6 libraries

• Retrosynthetic value:

  • Serves as a convergent nucleobase module for late-stage attachment of sugars, linkers, or labels
  • Orthogonality of S vs N reactivity permits sequential installation of substituents with high chemocontrol

These features make the scaffold suitable for medicinal chemistry exploration and nucleoside analog synthesis workflows.

Target Specificity

Not applicable. This product is a small-molecule research chemical, not an antibody, enzyme, or biologic with defined target binding parameters.

• No antigen/epitope, clone, isotype, or species reactivity information is relevant to this compound type.