Analytical QC: TLC (hexanes/EtOAc), GC–MS or LC–MS for identity/purity; 1H/13C NMR for structural confirmation; IR for C=O verification.
Purification: flash column chromatography on silica gel using hexanes/EtOAc gradients; avoid prolonged exposure to strong acids/bases on silica to minimize side reactions.
For any specific application (chemical transformation, method development), consult the primary literature and adapt conditions to your substrate and scale.
Biological Roles
This product is offered for research and synthetic chemistry use and is not a biological reagent. No endogenous biological role is associated with 3-ethoxyspiro[3.5]nonan-1-one.
General context (informational):
Spiroaliphatic ketones are largely xenobiotic in biological systems; metabolism, when it occurs, typically involves carbonyl reduction (to secondary alcohols), Baeyer–Villiger-type oxidation (to lactones/esters), or oxidative dealkylation of alkoxy substituents via cytochrome P450 enzymes.
The rigid, saturated spiro motif is sometimes explored in medicinal chemistry as a scaffold to increase three-dimensionality (Fsp3) and modulate physicochemical properties such as solubility and permeability. Any such exploration remains purely at the research/chemical probe level and does not imply biological activity of this specific compound.
Use limitations:
For research use only. Not for diagnostic, therapeutic, or other clinical use.
If biological evaluation is planned, consider:
Establishing analytical methods (LC–MS/MS) to monitor metabolic soft spots (carbonyl, ethoxy cleavage) in microsomes/hepatocytes.
Profiling basic ADME physicochemical surrogates (logD, pKa, solubility) to inform assay design, recognizing that aliphatic ketones are generally neutral and hydrophobic.
Buffer Applications
Not typically applicable. 3-Ethoxyspiro[3.5]nonan-1-one is a neutral, hydrophobic organic building block and does not function as a buffering agent. It has limited aqueous solubility and no acid/base functionality in the physiological pH range.
Practical note:
If aqueous handling is necessary (e.g., bioconjugation method development), dissolve first in a water-miscible co-solvent (DMSO, DMF, or ethanol) and add to buffer with vigorous mixing, keeping final organic content within assay tolerances.
For extractions or wash steps, common buffers (phosphate, citrate) may be used to control pH during workup of reactions involving this ketone, but the compound itself does not contribute buffering capacity.
Green Alternatives
As a substrate/building block, the compound itself is not readily substituted by a “green alternative.” However, greener choices can be made for solvents and reagents used with this ketone.
Greener solvent choices (general guidance):
Replace chlorinated solvents (DCM, chloroform) with ethyl acetate, 2-MeTHF, or cyclopentyl methyl ether (CPME) where compatible.
Prefer water/ethanol/i-PrOH for reductions when using borohydrides or catalytic hydrogenations that tolerate protic media.
Use 2-MeTHF or MTBE instead of diethyl ether to reduce volatility and peroxide risk (still monitor peroxides as needed).
Comparison snapshot (general):
DCM vs EtOAc: EtOAc is biodegradable, lower toxicity; may require temperature control for exothermic reactions and can participate in transesterification under strong base.
THF vs 2-MeTHF: 2-MeTHF often allows similar organometallic performance with improved safety profile (bio-based origin, higher bp); water content should be controlled.
Et2O vs CPME: CPME exhibits low peroxide formation rate and broader liquid range; check solubility for organometallics.
Greener reagents/process:
Baeyer–Villiger: consider H2O2/urea adduct or Oxone® systems in place of mCPBA where selectivity permits.
Reductions: catalytic hydrogenation (H2, Pd/C or Raney Ni) can replace stoichiometric hydrides for some targets, reducing waste.
Workup/waste: employ in-line scavengers and solvent recycling; select low-energy purification (e.g., crystallization) when possible.
Note: Always validate performance with small-scale trials when switching to greener media, as ring strain in cyclobutanones can alter reactivity/selectivity under new conditions.
Pharmaceutical Uses
Not an excipient and not intended for clinical use. This item is supplied for research and laboratory synthesis only.
General formulation context (informational):
Spiroaliphatic ketones are occasionally evaluated as discovery-stage intermediates or motifs within small-molecule lead series to adjust molecular shape and physicochemical properties. Any such use is limited to preclinical research chemistry.
As a neat substance, 3-ethoxyspiro[3.5]nonan-1-one has no recognized pharmacopeial monograph and is not used as a standard excipient (e.g., binder, solvent, stabilizer).
If considering formulation-like studies in research:
Solubilization: employ co-solvents (EtOH, PEG 400, propylene glycol), surfactants (Tween 80), or lipid vehicles for in vitro dosing solutions; confirm chemical stability in chosen vehicle.
Stability screening: monitor for carbonyl reduction/oxidation and potential transethoxylation or hydrolysis under acidic/basic conditions.
Compliance reminder:
For research use only. Not for human or animal therapeutic, diagnostic, or clinical applications.
Physical Properties
Item-specific specifications:
Appearance: Not specified for this item; refer to CoA/Spec Sheet.
Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
Other physico-chemical specs (bp, mp, density, UV cutoff, water/peroxide/metal limits): Not specified for this item; refer to CoA/Spec Sheet.
Literature/computed values (for context; not item specifications):
Empirical formula (from structure rationale): C11H18O2 (informational)
Calculated exact mass: ~182.1307 Da (informational)
Functional profile: neutral, non-aromatic ketone with an alkoxy substituent; expected to be a colorless to pale liquid or low-melting solid depending on purity and packing (general expectation for similar spiroketones).
Estimated logP: moderately lipophilic (cLogP likely in the ~2–3 range for related aliphatic spiroketones with an ethoxy group).
Volatility: moderate; ketones of this size commonly boil in the ~190–230 °C range at 1 atm, though actual bp depends on exact structure and purity (literature analogy).
Solubility: expected miscibility with common organic solvents (Et2O, DCM, THF, AcOEt, hexanes); low solubility in water (general for aliphatic ketones of this MW).
General notes for handling based on class behavior:
Carbonyl absorption strong near 1710–1740 cm⁻¹ (IR) for cycloalkanones; ring strain may shift slightly higher.
1H/13C NMR: characteristic carbonyl carbon around 205–215 ppm (cyclobutanone often deshielded); ethoxy CH3 triplet (~1.2–1.3 ppm), CH2 quartet (~3.4–3.7 ppm).
Quality and Grades
Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
Guidance on grades (general information for interpretation):
Research/Bulk grade: often suitable for synthesis and method development; impurity profile may not be fully optimized for trace analysis.
Purified/Distilled grade (if provided): indicates additional purification steps to reduce residual solvents or high-boiling impurities, which can be crucial for moisture- or base-sensitive transformations.
HPLC/UV grade (if applicable): manufactured to minimize UV-absorbing impurities and particulates, intended for chromatographic use. For this spiroketone building block, HPLC grade is typically not relevant unless used as a chromatographic reference.
Stabilizers: Not specified for this item; refer to CoA/Spec Sheet. For ketones, stabilizers are uncommon; impurity control focuses instead on peroxides (less common than in ethers), residual solvents, and aldol-condensation byproducts.
Documentation: request CoA for batch-specific assay, GC purity, residual solvent profile, and water content (Karl Fischer) when your application requires stringent control.
Practical recommendations:
If using in base-sensitive steps (e.g., strong-enolate chemistry), pre-analyze by GC/GC–MS to ensure absence of low-level aldehydes, alcohols, or over-oxidation products.
For scale-up or medicinal chemistry campaigns, keep a consistent lot to avoid micro-variability in side-product profiles caused by trace acidity/basicity.
If optical/stereochemical purity ever becomes relevant (e.g., downstream chiral induction), confirm achirality or racemic composition by chiral analysis even though this compound is not expected to be chiral by name.
Reaction and Applications
This spirocyclic cyclobutanone is a versatile building block leveraging carbonyl reactivity and ring strain.
Representative applications (literature/general, not exhaustive):
Enolate chemistry: α-deprotonation with LDA/LHMDS affords enolates that can be alkylated, acylated, or trapped as silyl enol ethers. Cyclobutanone enolates exhibit enhanced reactivity; careful temperature control minimizes ring opening.
Nucleophilic addition: organomagnesium/organolithium reagents add to the ketone to give tertiary alcohols. Steric/directional effects from the spiro junction can modulate diastereoselectivity.
Baeyer–Villiger oxidation: peracids (mCPBA) or ketone monooxygenases convert the cyclobutanone into the corresponding lactone; migratory aptitude and ring strain favor insertion with potential ring expansion.
Ring-expansion strategies: oxidative or rearrangement chemistry (e.g., Wolff-type, semipinacol after appropriate activation) can selectively expand the four-membered ring, giving access to medium rings with spiro retention.
Reductive transformations: NaBH4 or metal hydrides reduce the carbonyl to a secondary alcohol; subsequent derivatization (esterification, carbonate formation) provides polarity handles.
Heteroatom introduction: formation of oximes/hydrazones for downstream Beckmann or Wolff–Kishner-type modifications; tosylhydrazone generation can enable ring contraction/expansion depending on conditions.
Cross-coupling precursors: α-halogenation of the enol/enolate followed by substitution can introduce handles for further cross-coupling (e.g., via enol triflate formation and Pd-catalyzed coupling).
Use cases in discovery chemistry (general):
Incorporation as a rigid, lipophilicity-tuned motif to increase 3D character (Fsp3) of fragments/leads.
Scaffold hopping: spiro[3.5] frameworks serve as bioisosteres for bicyclic aliphatic scaffolds, modulating metabolic stability and permeability while maintaining compact size.
Reaction Conditions
General conditions for common transformations (literature guidance; adjust to your system):
Enolate generation/alkylation:
Base: LDA or LiHMDS (1.1–1.5 eq)
Solvent: anhydrous THF or DME
Temperature: −78 to −20 °C for deprotonation; 0 to rt for electrophile addition
Notes: slow addition of electrophile; quench at low temperature to minimize side reactions (ring opening/aldol).
Nucleophilic addition to carbonyl (RMgX/RLi):
Solvent: Et2O or THF
Temperature: −78 to 0 °C (RLi); 0 to rt (Grignard)
Workup: saturated NH4Cl or aqueous NH4Cl/NaHCO3; monitor carefully due to ring strain.
Baeyer–Villiger oxidation:
Reagent: mCPBA (1.2–2.0 eq, buffered), or peracetic acid
Solvent: DCM or EtOAc
Temperature: 0 °C to rt
Additives: NaHCO3 to neutralize acid; monitor to control over-oxidation.
Reduction to alcohol:
Reagent: NaBH4 (MeOH/EtOH, 0 to rt) or LiAlH4 (THF, 0 to rt)
Notes: LAH may reduce further under forcing conditions; quench carefully.
Enol triflate formation and cross-coupling:
Reagents: Tf2O, 2,6-lutidine (or pyridine), −78 to 0 °C (THF/DCM)
Coupling: Pd(0) catalyst (e.g., Pd(PPh3)4, 1–3 mol%), base (Cs2CO3), solvent (DMF/THF), 50–80 °C
Ketal protection:
Reagents: ethylene glycol, catalytic TsOH or PTSA
Solvent: toluene, Dean–Stark to remove water
Yields: Highly substrate/condition dependent; for analogous spirocyclobutanone chemistry, isolated yields of 50–85% are typical for well-optimized steps (literature ranges). Always optimize on small scale first.
Safety and Handling
Item-specific hazard data:
GHS classification, signal word, H-statements, pictograms: Not specified for this item; refer to SDS.
General safety guidance for aliphatic ketones and spirocycloalkanones (informational; consult SDS for authoritative instructions):
Likely hazards: combustible liquid; may cause skin and eye irritation; vapor may cause drowsiness or dizziness at elevated concentrations (by analogy to similar ketones).
Personal protective equipment (PPE): lab coat, safety glasses or chemical splash goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a chemical fume hood to minimize inhalation exposure.
Handling: avoid inhalation of vapors/mists; prevent skin contact. Keep away from ignition sources and static discharge. Ground containers when transferring flammable liquids.
Storage incompatibilities: separate from strong oxidizers (e.g., peroxides, chromates), strong reducing agents, and strong bases/acids that could catalyze aldol/enolization or cleavage reactions.
Spill/accidental release: absorb with inert material (vermiculite, sand), collect for disposal. Ventilate area and eliminate ignition sources.
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 present and easy to do; continue rinsing.
Ingestion: rinse mouth; do not induce vomiting; seek medical advice.
Fire-fighting: use dry chemical, CO2, alcohol-resistant foam. Combustion may produce CO/CO2; firefighters should wear SCBA.
Waste: dispose in accordance with local regulations; ketone-containing organic waste stream.
Always refer to the product SDS for definitive GHS classification and response measures.
Solvent Selection
Applicability: This product is an organic substrate/building block rather than a solvent. However, solvent choice is important for its handling and reactions.
General solvent behavior (literature/general):
Polarity class: moderately nonpolar to weakly polar substrate; dissolves well in common organic solvents.
Expected miscibility: high solubility in ethers (THF, MTBE), chlorinated solvents (DCM, chloroform), and esters (EtOAc); good solubility in aromatic and aliphatic hydrocarbons (toluene, heptane). Poor aqueous solubility is expected for this aliphatic ketone.
Dielectric considerations: for enolate chemistry and nucleophilic additions, polar aprotic solvents (THF, DME, DMF, DMSO) often enhance reactivity and control aggregation of organometallic bases.
Choosing a solvent by transformation type:
Enolate formation/alkylation: anhydrous THF, MTBE, or DME at −78 to 0 °C provides good solubility and control with LDA/LHMDS.
Nucleophilic additions (e.g., organolithium/Grignard to carbonyl): ether solvents (Et2O, THF) or toluene/THF mixtures balance reactivity and selectivity; low temperatures recommended to manage cyclobutanone ring strain.
Oxidations/reductions: DCM or EtOAc for peracid oxidations; MeOH/EtOH/i-PrOH or THF for borohydride/metal hydride reductions.
Catalysis (hydrogenation/isomerization): alcohols or toluene under H2 with appropriate catalysts; monitor for over-reduction of the carbonyl.
Practical tips:
Dry and degas solvents where organometallics or moisture-sensitive steps are involved.
Avoid strongly basic alcoholic media if ring-opening or transethoxylation is a concern.
For crystallization or purification, hexanes/EtOAc or heptane/EtOAc systems often provide good selectivity for aliphatic ketones.
Storage and Reconstitution
Item-specific storage/shipping:
Storage conditions: Room temperature (per Product Data).
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 for this class of compounds:
Container: store in a tightly closed, chemically compatible bottle (amber glass recommended) to minimize light exposure and volatilization.
Atmosphere: for long-term storage, consider an inert headspace (N2/Ar) and inclusion of a desiccant in the outer container to limit moisture ingress.
Stability: aliphatic ketones are typically stable at ambient conditions; avoid prolonged exposure to strong acids/bases that could promote aldol-type side reactions or cleavage of the ethoxy substituent.
Freeze/thaw: not applicable; store as supplied. If a low-melting solid or viscous oil, gentle warming to room temperature may be used to liquefy before dispensing.
Preparation for use:
If moisture-sensitive chemistry is planned, dry the material prior to use by brief standing over molecular sieves (3Å/4Å) or by co-evaporation with dry solvent under inert atmosphere.
For solution preparation, use anhydrous solvents and prepare fresh working solutions. Record concentration, solvent, and date on secondary container labels.
Shelf-life and QC:
Inspect periodically by GC or NMR if stored for extended periods. Any unusual odor, color change, or precipitate warrants re-analysis before use.
Structure and Identity
Brief overview: 3-Ethoxyspiro[3.5]nonan-1-one is a spirocyclic aliphatic ketone bearing an ethoxy substituent. It serves as a compact, conformationally restricted building block for synthesis.
Item-specific (from Product Data):
SKU: E947131
Product name: 3-Ethoxyspiro[3.5]nonan-1-one
CAS: 1051379-48-6
PubChem CID: 54595141
Storage conditions: Room temperature
InChIKey: 290788 (as provided in Product Data)
SMILES: 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 (informational, not item specifications):
Likely functional groups: one cyclic ketone (spiro-cycloalkanone) and one ethoxy substituent (–OCH2CH3)
Representative 2D description: a spiro junction connects a four-membered cyclobutanone ring (bearing the C=O) and a six-membered cyclohexane ring; the ethoxy group is attached at C-3 of the cyclobutanone ring (relative to the carbonyl carbon as C-1).
Stereochemistry: overall molecule is achiral unless substituted asymmetrically elsewhere; no stereogenic centers implied by the name.
Spiro junction imposes conformational rigidity and 3D shape (increased Fsp3), useful in lead-optimization to enhance solubility and modulate permeability.
The cyclobutanone ring is strained, increasing the acidity of the α-protons and the reactivity of the carbonyl toward nucleophiles.
The ethoxy substituent provides a masked alcohol motif and a potential handle for substitution via SN1/SN2 at the ethyl or by deprotection/cleavage under specific conditions.
Synthetic Utility
Key functional elements and reactivity (general literature guidance):
Cyclobutanone carbonyl: heightened electrophilicity due to ring strain; facilitates nucleophilic additions and rearrangements.
α-Carbon chemistry: enol/enolate formation enables alkylation, acylation, halogenation, and enol triflate generation for cross-coupling.
Ethoxy substituent: provides a latent alcohol/surface polarity handle; can be transformed via oxidative cleavage or substitution after activation.
Named/typical transformations:
Baeyer–Villiger oxidation to spiro-lactones (mCPBA, peracetic acid, or H2O2-based systems); migratory aptitude can yield predictable regioselectivity.
Mukaiyama aldol using the silyl enol ether derived from the ketone with aldehydes/ketones under Lewis acid catalysis.
Corey–Chaykovsky epoxidation of the carbonyl (via sulfonium ylide) to give epoxides that may undergo ring-opening with control induced by the spiro framework.
Wolff–Kishner/Bamford–Stevens-type sequences on hydrazone/tosylhydrazone derivatives for deoxygenation or skeletal editing.
Enol triflate formation (Tf2O, base) followed by Pd-catalyzed cross-couplings to append aryl/vinyl groups at the α-position.
Strategic value:
Rigid, compact spiro scaffold enhances 3D character (Fsp3), serving as a bioisosteric element for bicyclic aliphatic units in scaffold hopping.
The combination of ring strain and carbonyl functionality allows ring expansion or contraction to access otherwise challenging ring sizes.
Practical considerations:
Temperature control is critical in base- or acid-catalyzed steps to avoid undesired ring cleavage.
Protecting-group strategy is usually minimal; however, transient protection as ketals may be used when aggressive nucleophiles are required elsewhere in a sequence.
Target Specificity
Not applicable. This product is a small-molecule synthetic building block and is not an antibody, probe, or biological targeting agent. No target specificity, epitope, or isotype information applies.
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