4-Chloromethyl-[1,3]dioxane - ≥95% , CAS No.1121-62-6

CAS: 1121-62-6 Cat. No.: C1038982 Formula: C₅H₉O₂Cl Peso molecolare: 136.57 Numero EC: 155-187-2 PubChem CID: 4985599

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifiche e purezza

≥95%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥95%

Nomi e identificatori

Sorrisi canonici

C1COCOC1CCl

IUPAC Name

4-(chloromethyl)-1,3-dioxane

InChIKey

GKUCVLXFBHZZDE-UHFFFAOYSA-N

INCHI

1S/C5H9ClO2/c6-3-5-1-2-7-4-8-5/h5H,1-4H2

Isomeri SMILES

C1COCOC1CCl

PubChem CID

4985599

Peso molecolare

136.57

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Dioxanes
      • Subclass 1,3-dioxanes

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Dioxanes
• Subclass: 1,3-dioxanes
• Intermediate Tree Nodes: Not available
• Direct Parent: 1,3-dioxanes
• Alternative Parents: Oxacyclic compounds Acetals Organochlorides Hydrocarbon derivatives Alkyl chlorides
• Molecular Framework: Aliphatic heteromonocyclic compounds
• Substituents: Meta-dioxane - Oxacycle - Acetal - Organic oxygen compound - Hydrocarbon derivative - Organooxygen compound - Organochloride - Organohalogen compound - Alkyl halide - Alkyl chloride - Aliphatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as 1,3-dioxanes. These are organic compounds containing 1,3-dioxane, an aliphatic six-member ring with two oxygen atoms in ring positions 1 and 3.
• 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

Proprietà chimiche e fisiche

• Peso molecolare: 136.580 g/mol
• XLogP3: 0.800
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 136.029 Da
• Monoisotopic Mass: 136.029 Da
• Topological Polar Surface Area: 18.500 Ų
• Heavy Atom Count: 8
• Formal Charge: 0
• Complexity: 67.400
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 1
• 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 antibody/assay protocols apply to this small-molecule reagent. For practical usage, see Reaction Conditions for representative setups for SN2 substitutions, halide exchange, and subsequent transformations. Always tailor equivalents, solvent, and temperature to your specific nucleophile and scale, and validate by TLC/GC/LC-MS.

Biological Roles

This compound is a synthetic organic building block with no established endogenous biological role.

• Mode of action in biology: None known; it is not a metabolite or cofactor. The 1,3-dioxane ring is an acetal motif occasionally encountered in prodrugs or protecting groups, but this product is intended strictly for chemical synthesis.
• Reactivity considerations in bio-context (general): Primary alkyl chlorides can alkylate nucleophiles (thiols, amines), which is why strict laboratory handling is required; no biological utility is implied.

Research use note: For research use only (per product data). Do not apply to clinical or diagnostic procedures.

Buffer Applications

Not typically applicable. 4-Chloromethyl-[1,3]dioxane is not a buffering agent and is incompatible with standard aqueous buffer systems (risk of hydrolysis/substitution). For practical usage, see Reaction & Applications and Reaction Conditions tabs.

Green Alternatives

Consider greener choices at two levels: (a) the electrophile identity, and (b) the process solvents and conditions.

• Alternative electrophiles to reduce chlorinated waste:
  • 4-(Mesyloxymethyl)- or 4-(tosyloxymethyl)-1,3-dioxane can offer superior leaving groups and may be prepared in situ from the alcohol; they avoid chlorinated byproducts but add a sulfonate step.
  • Carbonate or leaving groups derived from green reagents (e.g., dimethyl carbonate) may be applicable in some substitution manifolds.
• Process solvents (comparative, literature-general):
  • Polar aprotic: Replace DMF/DMSO with safer MeCN or propylene carbonate when feasible.
  • Ethers: 2-MeTHF or CPME can substitute for THF/MTBE offering better sustainability and higher boiling points.
  • Chlorinated solvents: Prefer EtOAc or MeTHF over DCM/toluene when solubility and rate allow.

Trade-offs:

• Sulfonate leaving groups increase molecular weight and may complicate E-factor despite avoiding chlorides.
• Greener solvents can alter rate/selectivity in SN2; small-scale screens are recommended.

Guidance: Begin solvent scouting in MeCN or 2-MeTHF, monitor by GC or HPLC, and benchmark against a conventional solvent (THF or DMF) to quantify performance and environmental impact.

Pharmaceutical Uses

No pharmacopeial or excipient status is provided for this item. It may serve as a synthetic intermediate in medicinal chemistry routes, but it is not intended for human or veterinary administration.

• Item-specific regulatory/compendial status: Not specified for this item; refer to CoA/Spec Sheet.
• Formulation role: None; this material functions as a reactive building block and is unsuitable as an excipient.

Note: All uses are for research and development in a laboratory environment only.

Physical Properties

Item-specific specifications (BP/MP/density/refractive index/assay/UV cutoff/trace metals/peroxides/water): Not specified for this item; refer to CoA/Spec Sheet.

General/literature-leaning insights (for context only):

• Phase: Typically a low- to mid-boiling organic liquid for many small 1,3-dioxane derivatives; exact appearance for this SKU is not specified.
• Expected polarity: Moderately polar due to the acetal oxygens, yet overall neutral and aprotic; miscibility anticipated with common organic solvents (e.g., ethers, chlorinated solvents, esters) and limited solubility in water.
• Partition behavior: Primary chlorides on oxygenated rings tend to show modest lipophilicity; exact logP for this compound is not established here.
• Volatility/odor: Comparable cyclic acetals can be volatile; handle in a fume hood.

Important note: Use these general statements only as orientation. For precise values relevant to your method (e.g., density at 20 °C, GC purity, residual solvents, Karl Fischer water), please consult the item’s CoA/Spec Sheet.

Quality and Grades

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

Interpretation and guidance:

• When provided, assay (GC/LC), residual solvents, and stabilizer content define suitability for sensitive applications (e.g., nucleophile-specific alkylations or medicinal chemistry routes). For electrophiles such as 4-chloromethyl-[1,3]dioxane, trace alcohols/water can consume reagent; water and acid numbers are therefore especially relevant.
• If an inhibitor/stabilizer is listed on the CoA, it is typically to suppress hydrolysis or undesired polymerization; removal (e.g., by short-path distillation or brief passage through basic alumina) may be appropriate before use, depending on your application.
• For chromatography-sensitive applications, low UV background and low nonvolatile residue (NVR) are advantageous. If an “HPLC” or “GC” grade is available, it generally reflects tighter control of these parameters.
• Lot-specific documentation: Always verify assay, identity (NMR/GCMS), and impurity profile on the CoA for your lot. If a specification is critical to your method (water, halide content, UV cutoff, metals), treat as “not specified” until confirmed in writing by the CoA/spec sheet.

Reaction and Applications

4-Chloromethyl-[1,3]dioxane is a versatile electrophile for constructing 4-(substituted-methyl)-1,3-dioxane derivatives and for installing a 1,3-dioxanyl-methyl unit as a masked, oxygen-rich handle.

Representative applications (literature/general):

• SN2 alkylation of heteroatom nucleophiles: Formation of 4-(alkoxymethyl)-, 4-(thiomethyl)-, or 4-(aminomethyl)-1,3-dioxanes using alkoxides, thiolates, or amines, respectively. Azide displacement (NaN3) provides a route to 4-(azidomethyl)-1,3-dioxane for click elaboration.
• Carbon nucleophiles: Cyanide substitution affords 4-(cyanomethyl)-1,3-dioxane; deprotection/oxidation sequences can translate this into carboxamide/acids.
• Halide exchange/activation: Conversion to the corresponding bromide/iodide (e.g., via halide exchange) or sulfonate (e.g., tosylate/mesylate after substitution to the alcohol) for enhanced leaving group ability.
• Reductive manipulations: Hydrogenolysis or metal-mediated reduction of the C–Cl to 4-methyl-1,3-dioxane (with appropriate catalysts/conditions).
• Hydrolysis to alcohol: Nucleophilic substitution with hydroxide or buffered hydrolysis can yield 4-(hydroxymethyl)-1,3-dioxane, a useful intermediate.
• Organometallics: Under controlled conditions, magnesium insertion can generate a 4-(1,3-dioxanyl)methyl Grignard-type species for further C–C bond formation (ensure strict anhydrous handling).

Practical tips:

• Favor SN2 by using polar aprotic solvents and moderate temperatures; avoid strong bases that might induce elimination or ring cleavage.
• Maintain neutral to basic, non-acidic conditions to preserve the acetal ring during transformations and workup.

Reaction Conditions

Guidance below reflects general literature practices for primary-alkyl-chloride SN2 chemistry on oxygenated rings. Optimize for your substrate and scale.

• Nucleophilic substitution (O/N/S nucleophiles):
  • Solvents: MeCN, DMF, DMSO, or 2-MeTHF/THF (dry).
  • Bases: K2CO3, Cs2CO3, NaH (for alkoxides), or tertiary amines, depending on nucleophile strength.
  • Temperature: 20–80 °C; higher temperatures often accelerate conversion for weaker nucleophiles.
  • Stoichiometry: 1.1–1.5 equiv nucleophile; 1.5–2.5 equiv base when generating alkoxides in situ.
  • Typical times: 2–18 h depending on nucleophile and solvent.
• Azide displacement:
  • Solvent: DMF or MeCN; NaN3 (1.5–2.0 equiv).
  • Temperature: 25–80 °C; monitor by TLC/GC.
• Halide exchange (Finkelstein-type):
  • Reagent: NaI in acetone or MeCN.
  • Conditions: Reflux until complete; precipitated NaCl drives equilibrium.
• Formation of alcohol:
  • Reagents: Aqueous NaHCO3/NaOH (mild) or Ag2O/H2O for halide to alcohol conversion; maintain near-neutral pH to limit acetal cleavage.
• Workup/purification:
  • Quench with water or buffer at neutral pH; extract with EtOAc or MTBE. Avoid strong acids during washes.
  • Purify by flash chromatography on silica pre-treated with a small amount of base (e.g., 0.5–1% Et3N in eluent) to minimize acetal hydrolysis.

Note: Yields and exact parameters are substrate- and nucleophile-dependent; confirm by small-scale scouting. Use anhydrous conditions and exclude strong acids to preserve the acetal.

Safety and Handling

Product-specific GHS information (signal word, hazard statements, pictograms, classification): Not specified for this item; refer to SDS.

General safety considerations for primary alkyl chlorides and cyclic acetals (for guidance only; defer to SDS):

• Hazards: May be harmful if inhaled or absorbed through skin; can cause skin/eye irritation. Primary chlorides are electrophilic and may cause irritation to mucous membranes. Avoid inhalation of vapors and contact with skin/eyes.
• Reactivity: Susceptible to SN2 reactions with strong nucleophiles (amines, thiolates, alkoxides). Hydrolysis under strongly acidic conditions can open or cleave the acetal ring.
• Incompatibilities: Strong bases or nucleophiles (risk of exothermic substitution/elimination), strong acids (acetal hydrolysis), strong oxidizers.
• PPE: Lab coat, nitrile gloves (change regularly), splash goggles; use in a certified fume hood. Consider a face shield for scale-up or when there is splash risk.
• First aid (overview):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin: Wash with soap and water; remove contaminated clothing.
  • Eyes: Rinse cautiously with water for several minutes; remove contact lenses if easy to do; seek medical attention if irritation persists.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical advice.
• Storage: Per product data, store at room temperature. Keep tightly closed, in a dry, well-ventilated place; protect from moisture and strong acids/bases. Segregate from oxidizers.

Always consult the official SDS for definitive hazard and response information.

Solvent Selection

This product is a reactive organic building block rather than a solvent. Solvent selection pertains to its use in reactions and workups:

• Polarity and solubility (general): The 1,3-dioxane ring imparts moderate polarity; compound is typically soluble in common organic solvents such as dichloromethane, THF, ethyl acetate, acetonitrile, and toluene (literature/general behavior of small cyclic acetals).
• Choosing a medium for SN2 substitutions:
  • Polar aprotic solvents (e.g., DMF, DMSO, MeCN) often accelerate SN2 on primary chlorides.
  • Ethers (THF, MTBE) are suitable when using organometallics or moisture-sensitive bases.
  • Avoid strongly acidic media that promote acetal hydrolysis.
• Workup solvents: Ethyl acetate/hexanes systems or toluene/EtOAc are common for extraction and chromatography of oxygenated alkyl chlorides.

For solvent-grade specifications (water, peroxides, UV cutoff), none are item-specific here; consult the solvent’s own CoA when optimizing your reaction.

Storage and Reconstitution

• Storage (product-specific): Store at room temperature (per product data). Keep container tightly closed in a dry, well-ventilated place. Protect from moisture, strong acids (risk of acetal hydrolysis), and strong bases/nucleophiles.
• Inert atmosphere: While not strictly required, storing under dry nitrogen/argon and using desiccants can extend shelf life by minimizing hydrolysis.
• Stability: Cyclic acetals are generally stable under neutral, anhydrous conditions. Avoid prolonged exposure to acidic environments and elevated humidity.
• Reconstitution: Not applicable; supply form and appearance are not specified for this item. If solidification occurs upon cooling, warm gently and mix thoroughly before use.
• Handling prep: For moisture-sensitive operations, dry solvents and glassware; consider brief passage through a small plug of neutral/basic alumina if trace HCl or hydrolysis products are suspected.

Always refer to the lot-specific CoA and SDS for definitive handling and storage guidance.

Structure and Identity

Brief description: 4-Chloromethyl-[1,3]dioxane is a six-membered cyclic acetal (1,3-dioxane ring) bearing a primary chloromethyl substituent at the 4-position, making it a useful electrophilic building block for SN2 derivatization.

• CAS: 1121-62-6 (product-specific)
• PubChem CID: 4985599 (product-specific)
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula: C5H9ClO2 (literature)
• Molecular weight: ~136.58 g/mol (literature)
• Structural features (general description):
  • 1,3-dioxane ring (six-membered ring with two heteroatoms at positions 1 and 3), typically adopting chair conformations analogous to cyclohexane.
  • Primary chloromethyl group at C-4 (–CH2Cl), providing a good leaving group for bimolecular nucleophilic substitution.
  • No stereogenic centers in the unsubstituted 1,3-dioxane framework for this substitution pattern; ring conformers may interconvert.
• 2D structure in words: a saturated six-membered ring composed of two oxygens (positions 1 and 3) and four carbons; at the ring carbon opposite the 1,3-dioxa fragment (C-4), a –CH2Cl substituent projects exocyclicly.

Synthetic Utility

Functional group profile and reactivity:

• Electrophile: Primary chloromethyl group enables classic SN2 transformations with a broad range of nucleophiles, yielding 4-substituted-methyl 1,3-dioxanes.
• Acetal stability: The 1,3-dioxane is stable to many neutral/basic conditions, making it a convenient, oxygen-rich scaffold that survives numerous steps. It is cleavable under acidic aqueous conditions, enabling late-stage unmasking when desired.

Representative synthetic maneuvers (literature/general):

• N- and O-alkylations to introduce protecting/solubilizing handles; subsequent acetal hydrolysis can release functionalized primary alcohols or carbonyl equivalents depending on sequence.
• Convergent assembly: Use of 4-(1,3-dioxanyl)methyl units as masked diol/carbonyl surrogates; post-substitution oxidation or reduction diversifies outputs.
• Cross-coupling via halide activation: Halide exchange to iodide followed by metal–halogen exchange can provide organometallic reagents for C–C bond formation with electrophiles (e.g., aldehydes, acid chlorides).
• Cascade strategies: Azide displacement → Staudinger/thiol–ene/click provides rapid entry to amino- or triazole-bearing dioxane derivatives, useful in library synthesis.

Selectivity and protection:

• Favor SN2 by minimizing sterics and employing polar aprotic solvents. Avoid acidic media to preserve the acetal during workup and purification.

Target Specificity

Not applicable. This is a small-molecule reagent, not a biological targeting agent (no antigen/epitope/clone/isotype information). Refer instead to Synthetic Utility and Reaction & Applications for relevant use cases.