3-Ethyloxolane-2,5-dione , CAS No.14035-81-5

CAS: 14035-81-5 Cat. No.: E1311071 Formula: C₆H₈O₃ Molecular Weight: 128.13 EC Number: 884-623-0

Storage

Room temperature

Shipped In

Normal

Specifications

Storage

Room temperature

Shipped In

Normal

Names and Identifiers

Canonical Smiles

CCC1CC(=O)OC1=O

IUPAC Name

3-ethyloxolane-2,5-dione

InChIKey

YRTGWRSQRUHPKX-UHFFFAOYSA-N

INCHI

1S/C6H8O3/c1-2-4-3-5(7)9-6(4)8/h4H,2-3H2,1H3

Molecular Weight

128.13

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic acids and derivatives
    • Class Carboxylic acids and derivatives
      • Subclass Dicarboxylic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Organic acids and derivatives
• Class: Carboxylic acids and derivatives
• Subclass: Dicarboxylic acids and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Dicarboxylic acids and derivatives
• Alternative Parents: Tetrahydrofurans Carboxylic acid anhydrides Lactones Oxacyclic compounds Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aliphatic heteromonocyclic compounds
• Substituents: Dicarboxylic acid or derivatives - Tetrahydrofuran - Carboxylic acid anhydride - Lactone - Oxacycle - Organoheterocyclic compound - Organic oxygen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Carbonyl group - Aliphatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as dicarboxylic acids and derivatives. These are organic compounds containing exactly two carboxylic acid groups.
• 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

Chemical and Physical Properties

• Molecular Weight: 128.130 g/mol
• XLogP3: 0.500
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 1
• Exact Mass: 128.047 Da
• Monoisotopic Mass: 128.047 Da
• Topological Polar Surface Area: 43.400 Ų
• Heavy Atom Count: 9
• Formal Charge: 0
• Complexity: 150.000
• 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

Not applicable. No validated bioassay protocols (e.g., WB, IHC, IF, FC) are associated with this chemical reagent.

General synthetic handling (informational):

• For amide formation: Dissolve the amine (1.0 equiv) in dry DCM, cool to 0 °C, add 3‑Ethyloxolane‑2,5‑dione (1.05 equiv) portionwise; stir 1–2 h at 0–25 °C; concentrate and triturate with ether/hexanes to isolate the amic acid. For imide, heat in toluene with Dean–Stark until cyclization completes (monitor by IR/NMR).
• For half‑ester: Stir the anhydride (1.0 equiv) with ROH (2–5 equiv) and catalytic DMAP (5 mol%) at 0–25 °C; remove solvent, neutralize residual acid, and purify by column chromatography.

Note: These are literature‑style examples to illustrate use; optimize to your substrates and consult the primary literature.

Biological Roles

This product is a synthetic, ethyl‑substituted cyclic anhydride and does not have known endogenous biological roles.

General biochemical context (literature/general):

• Parent motif: Succinic acid and succinate esters are central to metabolic pathways (e.g., the tricarboxylic acid cycle). However, 3‑ethyl substitution renders this compound non‑natural and not part of primary metabolism.
• Reactivity in biological media: Cyclic anhydrides rapidly hydrolyze in aqueous environments to corresponding acids; they may acylate nucleophilic residues in proteins (lysine, serine) under certain conditions, a behavior exploited analytically with other anhydrides (e.g., acetic anhydride) but not typically with alkyl‑substituted succinic anhydrides in vivo.
• Use in bioconjugation (conceptual): Anhydrides can form amide linkages with amines on biomolecules; selectivity and control require buffered, mildly basic aqueous–organic media, but hydrolysis competes strongly. For this substituted anhydride, such applications are niche and require optimization.

Caveat:

• No claims of biological activity, therapeutic benefit, or clinical utility are made. Any use is restricted to research in controlled laboratory settings. For experiments with biological matrices, assess cytotoxicity/irritancy and hydrolysis kinetics independently.

Buffer Applications

Not typically applicable. 3‑Ethyloxolane‑2,5‑dione is a reactive cyclic anhydride that hydrolyzes in water and will not serve as a stable buffering component.

Practical note (if used near aqueous conditions):

• If amide formation with biomolecules is desired, employ mixed aqueous–organic systems (e.g., MeCN/H2O or DMF/H2O) with careful pH control (often pH 7.5–9) and rapid addition to outcompete hydrolysis. However, due to rapid ring opening and limited selectivity, standard biochemical buffers (HEPES, phosphate, Tris) are preferred for maintaining pH, and the reaction should be treated as an acylation, not a buffering application.

Green Alternatives

Perspective on greener choices focuses on reagent and solvent selection, waste minimization, and safer workup.

• Relative to acid chlorides: Using a cyclic anhydride like 3‑ethyloxolane‑2,5‑dione avoids generation of stoichiometric HCl and often proceeds without auxiliary coupling reagents, lowering salt waste. Workups typically produce a carboxylate byproduct rather than chloride.

• Solvent choices (greener options):

  • Consider 2‑methyltetrahydrofuran (2‑MeTHF) or cyclopentyl methyl ether (CPME) instead of DCM for acylations; both can enable efficient extractions and are derived (2‑MeTHF) from biomass. Acetonitrile and ethyl acetate are often preferable to chlorinated solvents where compatible.

• Catalysis and energy:

  • Use nucleophilic catalysts (DMAP) at ambient temperature to reduce heating. For imide formation, azeotropic dehydration in toluene or xylene can be replaced with solvent‑free melt conditions in some cases (verify thermal stability first).

• Comparison table (general):

  • DCM vs 2‑MeTHF: DCM offers excellent solvency but is chlorinated and has higher environmental impact; 2‑MeTHF is bio‑based, less dense than water, and facilitates phase separation.
  • Acid chloride route vs anhydride route: Chloride gives faster reactions with hindered amines but produces corrosive HCl; anhydride is milder, often selective, and safer to handle.

• Waste minimization:

  • Plan stoichiometry to minimize excess anhydride.
  • Recover and reuse solvents; consider in‑process controls (IR) to avoid overreaction and side‑product formation.

Note: Validate green substitutions on small scale to confirm kinetics and selectivity with this specific substrate.

Pharmaceutical Uses

No direct formulation or excipient role is specified for this item. As a reactive cyclic anhydride, 3‑Ethyloxolane‑2,5‑dione is generally unsuitable for inclusion in finished dosage forms.

General context in pharmaceutical process chemistry (literature/general):

• Synthetic intermediate: Cyclic anhydrides are widely used to introduce succinyl motifs and to form imides/amic acids in API intermediate synthesis. The ethyl substituent provides a handle to modulate sterics/lipophilicity in building blocks.
• Advantages over acid chlorides: Reduced corrosive byproducts (no HCl), often manageable at ambient temperature, and amenable to telescoped workups (amic acid precipitation, in situ cyclization).
• Considerations: Residual anhydride and hydrolysis products (monoacid/diacid) must be tightly controlled; validated quench and purge steps are necessary to meet impurity specifications.

Compliance:

• No pharmacopeial monograph is known for this specific substituted anhydride. Any use is for research and process development only. Do not use for human or veterinary 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.

Literature/general values and qualitative behavior (for context; not item specifications):

• Phase at ambient conditions: typically a low‑melting solid or viscous liquid for alkyl‑substituted succinic anhydrides; exact MP varies with substitution and enantiomeric ratio.
• Hydrolytic behavior: cyclic anhydride hydrolyzes in the presence of moisture to the corresponding 3‑ethylsuccinic acid (mono‑ or diacid depending on conditions).
• Solubility (qualitative): miscible with many aprotic organic solvents (e.g., dichloromethane, toluene, THF, acetonitrile); reacts with protic solvents (alcohols, water) to give half‑esters/acids over time.
• Volatility: lower volatility than unsubstituted succinic anhydride due to added ethyl substituent; best handled in a dry environment to minimize hydrolysis.
• Estimated molecular formula/mass (literature): C6H8O3; ~128.12 g/mol.

Not provided for this specific item (consult CoA/SDS or primary literature for numeric values):

• Melting/boiling point, density, refractive index, vapor pressure, pKa(s), logP, UV/Vis cutoff, water content/peroxide content, metal impurities.

Practical notes (general):

• Avoid prolonged exposure to humid air; weigh quickly in a dry box or under inert atmosphere when analytical accuracy is critical.
• For NMR, dry aprotic solvents (CDCl3, DMSO‑d6) are preferred; in CD3OD or D2O, ring opening occurs.

Quality & Grades

Item-specific grade/purity details:

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

General guidance for this compound class:

• For acylation chemistry and materials synthesis, researchers often select “reagent grade” or higher to minimize hydrolysis byproducts (monoacids/diacids). Low water content and low acid number are desirable for reproducible conversions.
• Chromatography/higher‑purity needs: If the compound is used as a derivatization reagent or in polymerizations, additional controls such as low UV‑absorbing impurities and narrow residual solvent profiles may be relevant (check CoA/SDS).
• Assay verification: Cyclic anhydrides can partially hydrolyze upon storage; titrimetric anhydride assays or quantitative NMR are common QA checks prior to critical reactions.
• Trace metals/ionic impurities: Typically not limiting for anhydrides used in organic synthesis; if using in catalytic transformations or electronics materials, request a spec with defined metal limits.

Documentation to consult:

• Certificate of Analysis (CoA): for the specific lot’s assay, byproducts (acid content), and water.
• Specification Sheet: for acceptance criteria, packaging, and any stabilizers.

Practical note:

• Minimize headspace humidity and repeated opening; consider aliquoting under dry nitrogen/argon to maintain grade over time.

Reaction & Applications

As a substituted cyclic anhydride, 3‑ethyloxolane‑2,5‑dione is a versatile acylating building block. Typical applications (literature/general):

• Amide/Imide synthesis:

  • Primary/secondary amines give amic acids under mild conditions (0–25 °C, DCM/THF/MeCN). Subsequent dehydration (thermal or using acetic anhydride, CDI, or Dean–Stark in toluene) yields 3‑ethylsuccinimides.
  • Diamines furnish bis‑amic acids and polyimides after cyclodehydration—useful for materials where an ethyl‑substituted succinate spacer modulates flexibility and Tg.

• Esterification and half‑ester formation:

  • Alcohols open the anhydride to mono‑esters (3‑ethylsuccinic half‑esters). Catalysis with DMAP/Et3N or acid catalysis can tune rates and selectivity. Diesters are accessible by subsequent esterification of the acid.

• Hydrolysis and salt formation:

  • Base‑catalyzed hydrolysis (NaOH, K2CO3, aqueous THF/MeCN) affords 3‑ethylsuccinic acid; neutralization yields defined salts for further transformations.

• Friedel–Crafts acylation (selected aromatics):

  • In the presence of Lewis acids (AlCl3, FeCl3), cyclic anhydrides can deliver acylated aromatics (succinylation). The ethyl substituent introduces an additional carbon framework for further elaboration.

• Carbon–carbon bond formations:

  • Anhydrides react with organocuprates (Gilman reagents) to form ketones (acyl substitution), offering a route to 3‑ethylsuccinyl‑derived ketones.

Practical tips:

• Control moisture; pre-dry glassware and solvents.
• For selective mono‑acylation of amines, employ sub‑stoichiometric base or use in situ base scavengers to avoid over‑acylation.
• Monitor by IR (anhydride bands ~1850/1780 cm⁻¹; literature) and NMR; disappearance of split carbonyl bands indicates consumption.

Reaction Conditions

General literature guidance (typical ranges; verify for your substrates):

• Amic acid formation (amine addition):

  • Solvent: DCM, THF, or MeCN (dry).
  • Temperature: 0 to 25 °C (ice bath start for scale to control exotherm).
  • Stoichiometry: 1.0–1.1 equiv anhydride per equiv amine.
  • Additives: Triethylamine (0–1.0 equiv) or DMAP (0.05–0.10 equiv) may accelerate; avoid strong bases that induce hydrolysis.
  • Time: 0.5–4 h; monitor by IR/NMR.

• Imide cyclization (from amic acid):

  • Solvent: toluene or xylene with Dean–Stark trap; alternatively Ac2O or AcOH as dehydrating media.
  • Temperature: reflux (110–140 °C depending on solvent) for 2–16 h.
  • Catalysts: AcONa or P2O5 (caution) can promote cyclodehydration.

• Half‑ester formation (alcohol opening):

  • Solvent: the alcohol itself or alcohol/CH2Cl2 (anhydrous).
  • Catalysts: DMAP (5–10 mol%) ± Et3N.
  • Temperature: 0–25 °C; times 1–6 h.

• Base hydrolysis to 3‑ethylsuccinic acid:

  • Media: THF/H2O or MeCN/H2O with NaOH (1–2 M aq.).
  • Temperature: 0–25 °C; then acidify to pH ~2 to precipitate the diacid.

• Acylation of aromatics (Friedel–Crafts):

  • Solvent: DCM, 1,2‑DCE, or nitrobenzene.
  • Catalyst: AlCl3 (1–2 equiv) or FeCl3.
  • Temperature: 0–25 °C initial, then warm to RT/reflux as needed; quench cautiously.

Yields: Strongly substrate‑dependent; many amic acid and half‑ester formations proceed in good to excellent yields (>70%) under optimized conditions (literature). Conduct small‑scale trials to establish kinetics/selectivity.

Safety & Handling

Authoritative safety information for this product is not specified in the Product Data; always consult the SDS before use.

Item-specific details:

• Signal Word, H‑Statements, GHS Classification, Pictograms: Not specified for this item; refer to SDS.
• Storage Conditions: Room temperature (as provided). Keep container tightly closed and dry.
• Shipped In: Normal (ambient) conditions (as provided).
• Research Use: For research use only.

General anhydride safety considerations (literature/general guidance):

• Hazards: Cyclic anhydrides are typically irritants/corrosives to skin, eyes, and respiratory tract; they may cause allergic respiratory reactions in sensitized individuals. Hydrolysis liberates carboxylic acids that are also irritants.
• Incompatibilities: Moisture/water (hydrolysis), strong bases (exothermic saponification), strong oxidizers, strong nucleophiles (uncontrolled acylation). Avoid contact with alcohols and amines unless intended for reaction.
• PPE: Chemical‑resistant gloves (e.g., nitrile), lab coat, splash goggles; use in a fume hood to control vapors/aerosols.
• First aid (overview; follow SDS): Eye/skin contact—immediately rinse with water for ≥15 minutes; remove contaminated clothing. Inhalation—move to fresh air; seek medical attention if symptoms persist. Ingestion—rinse mouth; do not induce vomiting; seek medical advice.
• Spill/cleanup: Absorb with inert material, avoid water addition that may generate heat/acids; collect for disposal per institutional and local regulations.
• Special risks: Moisture uptake can alter assay and stoichiometry in syntheses; handle under dry conditions for reproducibility.

Solvent Selection

Polarity and miscibility (general for cyclic anhydrides):

• Polarity class: moderately polar, electrophilic; dissolves well in aprotic organic solvents.
• Typical solvents: dichloromethane (DCM), chloroform, toluene, acetonitrile, ethyl acetate, THF, DMF, DMSO. Avoid protic solvents (water, alcohols) unless controlled ring‑opening is intended.

Choosing a solvent by application:

• N‑acylation (amic acid/imide formation): DCM, THF, or MeCN at 0–25 °C for controlled exotherm; DMF when substrates are poorly soluble (consider base scavenger or triethylamine).
• O‑acylation (half‑esters): corresponding alcohol as solvent with catalytic DMAP or acid/base catalysis; be aware of competing hydrolysis.
• Regioselective ring opening: Addition of amines at lower temperature in DCM/THF can favor formation of amic acids; heating or dehydrating conditions promote cyclization to imides.
• Friedel–Crafts acylation: non-coordinating solvents (e.g., DCM, nitrobenzene, 1,2‑dichloroethane) with Lewis acids, if applicable.

Comparisons (general):

• Versus acid chlorides: anhydrides are less moisture‑sensitive (no HCl release) and often milder; however, they can be less reactive toward hindered nucleophiles.
• Versus carboxylic acids: significantly more electrophilic, enabling room‑temperature acylations without coupling reagents.

Operational tips:

• Dry solvents rigorously; trace water increases monoacid formation.
• For scale‑up, select higher‑boiling solvents (toluene, xylene) to allow azeotropic water removal (Dean–Stark) during imide formation.

Storage & Reconstitution

Item-specific directions:

• Storage Conditions: Room temperature (as provided). Store tightly closed in a dry, well‑ventilated place.
• Shipped In: Normal ambient conditions.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.

General handling and stability for cyclic anhydrides:

• Moisture sensitivity: Hygroscopic hydrolysis converts the anhydride to mono/diacids over time, changing assay and reactivity. Keep desiccated; minimize exposure to humid air.
• Container: Use airtight amber glass where feasible; purge headspace with dry nitrogen/argon for prolonged storage.
• Aliquoting: For frequent use, prepare small aliquots under dry conditions to avoid repeated moisture ingress.
• Reconstitution: Not applicable; this is a neat chemical, not supplied as a lyophile. If solidified or viscous, gently warm (e.g., 30–40 °C) in a sealed container to aid transfer—avoid overheating.
• Stability checks: Periodically verify by IR (anhydride bands) or titration before critical reactions.

Disposal:

• Quench residues by controlled hydrolysis (ice/water under stirring, neutralize) and dispose of according to institutional and local regulations. Consult the SDS for detailed guidance.

Structure & Identity

Brief description: 3‑Ethyloxolane‑2,5‑dione is the 3‑ethyl derivative of oxolane‑2,5‑dione (succinic anhydride), i.e., a five‑membered cyclic anhydride bearing an ethyl substituent at the 3‑position. The 3‑position is stereogenic; commercial material is typically racemic unless otherwise specified.

Item-specific identifiers (from Product Data):

• CAS: 14035-81-5
• PubChem CID: 139667
• InChIKey: 445168 (as provided)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.

Item-specific naming:

• Preferred name: 3-Ethyloxolane-2,5-dione
• Common synonym (general): 3-ethylsuccinic anhydride (literature)

Literature/computed structural details (informational, not item specifications):

• Core scaffold: cyclic anhydride (oxolane-2,5-dione) ring containing one ring oxygen and two anhydride carbonyls at C2 and C5.
• Substitution pattern: ethyl group at C3 (alpha to both carbonyls), generating a stereocenter.
• Functional groups: cyclic carboxylic anhydride (highly electrophilic, hydrolyzable), aliphatic ethyl side chain.
• 2D description in words: a five‑membered ring comprised of –O–C(=O)–CH(R)–CH2–C(=O)–, where R = ethyl; the two carbonyls are anhydride carbonyls flanking the ring oxygen.

Molecular formula and mass:

• Molecular formula (literature): C6H8O3 (informational)
• Molecular weight (literature): ~128.12 g/mol (informational)

Note: Definitive structure, identifiers, and stereochemical composition for this specific lot should be confirmed on the CoA/Spec Sheet.

Synthetic Utility

Key functional elements:

• Cyclic carboxylic anhydride: bifunctional acyl donor enabling stepwise or simultaneous introduction of two carboxyl‑derived functions.
• Stereogenic center at C3: potential to generate diastereomeric products upon further functionalization; racemic starting material can be resolved downstream (e.g., via chiral amine/ester formation).

Typical transformations (literature/general):

• Nucleophilic ring opening:
  • With amines → amic acids; dehydration → imides (thermal, Ac2O, CDI, P2O5, or Dean–Stark in toluene/xylene).
  • With alcohols/phenols → half‑esters; further esterification → diesters.
  • With water/base → 3‑ethylsuccinic acid/salts.
• Acyl transfer to organocuprates → ketones (acyl substitution generating 3‑ethylsuccinyl ketones), useful in convergent assembly.
• Friedel–Crafts acylation of aromatics → aryl 3‑ethylsuccinyl ketones under Lewis acid catalysis.
• Activation downstream: Convert the resulting carboxylic acid to acyl chlorides, mixed anhydrides, or activated esters (NHS, PFP) for coupling cascades.

Retrosynthetic value:

• Serves as a compact synthon for masked 1,4‑dicarboxylate bearing an ethyl‑substituted stereocenter. Strategic for constructing substituted succinates, succinimides, and related heterocycles.

Practical considerations:

• Control regioselectivity and avoid double addition by temperature management and stoichiometry.
• Monitor by IR (anhydride bands ~1850/1780 cm⁻¹; literature) and LC/HPLC to track hydrolysis products that can complicate purifications.

Target Specificity

Not applicable. This product is a small‑molecule cyclic anhydride and is not an antibody, protein, or targeted biological reagent. No antigen/epitope specificity, clone, isotype, or species reactivity data are relevant.