N-(4-Chlorophenyl)glutarimide , CAS No.81305-70-6

CAS: 81305-70-6 Cat. No.: N928517 Formula: C₁₁H₁₀ClNO₂ Peso molecolare: 223.650 Numero EC: 661-395-9

Storage

Room temperature

Specifications

Condizioni di conservazione di stoccaggio

Room temperature

Nomi e identificatori

Sorrisi canonici

C1CC(=O)N(C(=O)C1)C2=CC=C(C=C2)Cl

IUPAC Name

1-(4-chlorophenyl)piperidine-2,6-dione

InChIKey

HXXVDRRWNNHFTI-UHFFFAOYSA-N

INCHI

1S/C11H10ClNO2/c12-8-4-6-9(7-5-8)13-10(14)2-1-3-11(13)15/h4-7H,1-3H2

Peso molecolare

223.650

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Piperidines
      • Subclass Phenylpiperidines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Piperidines
• Subclass: Phenylpiperidines
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylpiperidines
• Alternative Parents: Piperidinediones Delta lactams Chlorobenzenes N-substituted carboxylic acid imides Aryl chlorides Dicarboximides Azacyclic compounds Organopnictogen compounds Organonitrogen compounds Organochlorides Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Phenylpiperidine - Piperidinedione - Chlorobenzene - Delta-lactam - Halobenzene - Piperidinone - Aryl chloride - Aryl halide - Monocyclic benzene moiety - Benzenoid - Carboxylic acid imide, n-substituted - Carboxylic acid imide - Dicarboximide - Lactam - Azacycle - Carboxylic acid derivative - Organohalogen compound - Organooxygen compound - Organic nitrogen compound - Hydrocarbon derivative - Organic oxide - Carbonyl group - Organopnictogen compound - Organic oxygen compound - Organochloride - Organonitrogen compound - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as phenylpiperidines. These are compounds containing a phenylpiperidine skeleton, which consists of a piperidine bound to a phenyl group.
• 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: 223.650 g/mol
• XLogP3: 1.300
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 223.04 Da
• Monoisotopic Mass: 223.04 Da
• Topological Polar Surface Area: 37.400 Ų
• Heavy Atom Count: 15
• Formal Charge: 0
• Complexity: 256.000
• 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 item-specific tested biological or analytical application protocols are provided for this product. For synthetic use, follow general procedures for imide enolate formation, cross‑coupling of aryl chlorides, or imide reductions as outlined under Reaction Conditions, adjusting stoichiometry, temperature, and solvent based on small-scale optimization.

Biological Roles

Item-specific biological roles: Not specified for this item; no biological/physiological role is assigned. For research use only.

General background (non-clinical, literature context):

• The glutarimide ring system appears in several bioactive research molecules (e.g., as a conformationally constrained amide isostere). However, intrinsic biological activity of N‑(4‑chlorophenyl)glutarimide itself is not established here and should not be assumed.
• Imide motifs often modulate H‑bond acceptor capacity and planarity, properties exploited in medicinal chemistry to probe binding in enzyme/protein pockets. Any such use must be empirically validated for the specific target.

No claims are made regarding pharmacology, toxicity, or therapeutic potential. Consult primary literature if exploring target interactions in biochemical assays.

Buffer Applications

This compound is not a buffering agent and is not typically used to prepare biochemical buffers or control pH. If dissolved for biochemical assays, choose an appropriate assay buffer independently (e.g., phosphate, HEPES) and prepare compound stock solutions in DMSO or other miscible organic solvent before diluting into the assay medium as solubility permits.

Green Alternatives

As a solid reagent/intermediate, “green alternatives” focus on process choices rather than replacing the compound itself.

Greener process considerations (general):

• Solvent selection: Prefer low-toxicity, biorenewable, or low‑VOC options when feasible.
  • Examples for dissolving/processing imides:
    • Ethyl acetate and 2‑MeTHF can sometimes substitute for DCM/THF.
    • Acetonitrile may replace DMF when high boiling polar aprotic solvents are undesirable (balance with solubility needs).
• Bases/reagents: Use milder bases (e.g., carbonate) where possible; for enolate chemistry, consider solvent/temperature optimization to minimize waste and side reactions.
• Workups: Employ aqueous biphasic extractions minimizing halogenated solvents; use crystallization instead of chromatography when practicable.

Small comparison (general guidance):

• DMF/DMSO (traditional) vs 2‑MeTHF/EtOAc (greener)
  • Pros (DMF/DMSO): high solubility, broad reaction compatibility
  • Cons: high boiling, challenging removal, environmental burden
  • Pros (2‑MeTHF/EtOAc): lower toxicity/impact, easier recovery
  • Cons: lower solubility for some imides; may require heating or co‑solvents

Note: The compound itself contains a chloroarene; appropriate waste segregation for halogenated organics is recommended.

Pharmaceutical Uses

No excipient or pharmacopeial status is specified for this item; it is offered for research use only.

General discovery chemistry context (non-clinical):

• N‑aryl glutarimides serve as scaffolds/building blocks in medicinal chemistry campaigns due to their rigid, polar yet lipophilic balance. The para‑chloro substituent allows late‑stage diversification by cross‑coupling to rapidly explore SAR.
• Potential roles in preclinical workflows include: intermediate toward more complex heterocycles, fragment in library synthesis, or reference standard. Any formulation development would be purely for research screening and not for human/animal administration.

Physical Properties

Item-specific physical specifications (bp, mp, density, etc.): Not specified for this item; refer to CoA/Spec Sheet.

General/literature characteristics for N‑aryl glutarimides (for guidance only):

• Physical state: typically crystalline solids due to strong imide dipole and planarity of the N‑aryl imide.
• Solubility profile (literature/general):
  • Sparingly soluble in water (imide neutral, limited H‑bond basicity when N‑aryl).
  • Soluble in polar aprotic organics (DMSO, DMF, NMP); moderate solubility in acetone, ethyl acetate; limited in alkanes/hexanes.
• Acid/base: weakly acidic enolizable methylene at C‑3 (between the two carbonyls); N is anilide and not basic.
• logP/logD (qualitative, literature): moderate lipophilicity expected due to para‑chloro phenyl and imide; commonly logP ~1–2 for analogous N‑aryl imides (exact value not specified for this item).
• UV characteristics (general): aromatic chromophore with imide carbonyls; π→π* absorption in near‑UV; not specified for this item.

Note: For exact melting point, purity-related transitions, and analytical constants (UV cutoff, water content, residual solvents), consult the item-specific CoA/SDS.

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• What “research grade” typically implies: material suitable for general laboratory synthesis and screening; not certified for clinical, GMP, or food uses.
• Analytical control considerations for cyclic imides:
  • Identity confirmation: 1H/13C NMR (diagnostic imide carbonyls ~170–180 ppm), IR (imide C=O stretches ~1770–1710 cm−1), MS (M+ at ~223.6 Da for this structure, literature/computed), and HPLC for purity.
  • Residual solvents/water: Karl Fischer and GC are typical; specific limits are item-dependent. For this item: Not specified; refer to CoA/Spec Sheet.
  • Metals/inorganics: Not typically limiting for this class unless used in metal-catalyzed steps; for this item: Not specified; refer to CoA/Spec Sheet.
• Stabilizers/additives: None typically required for imides; any present would be indicated on the CoA. For this item: Not specified; refer to CoA/Spec Sheet.

Recommendation: Request the lot-specific CoA for exact assay, chromatographic purity, and analytical thresholds relevant to your application (e.g., medicinal chemistry, materials screening).

Reaction and Applications

N-(4-Chlorophenyl)glutarimide is a useful scaffold and intermediate in heterocycle and medicinal chemistry programs. Key application themes (general/literature):

• Enolate chemistry at C‑3 (between the two imide carbonyls):
  • Deprotonation with LDA/LHMDS (−78 to 0 °C) forms a stabilized imide enolate suitable for alkylation (primary alkyl halides), acylation, or Michael additions. Regeneration of the imide after trapping maintains the core.
• Ring opening/hydrolysis:
  • Under strong basic or acidic conditions, imides can hydrolyze to the corresponding amino acids/amides (for N‑aryl imides, conditions are harsher due to decreased N‑acyl activation). This enables synthesis of 5‑aminovaleramide/acid derivatives after N–Ar cleavage or via stepwise strategies.
• Reductive transformations:
  • Partial reductions (e.g., with borohydrides/metal hydrides) can access 3‑aminopiperidin‑2‑one motifs; full reductions may lead to diamides or lactams (method dependent, literature precedents on cyclic imides).
• Cross-coupling leveraging the para‑chloro handle (on the aryl ring):
  • The aryl chloride can undergo Pd‑catalyzed Suzuki, Buchwald–Hartwig (after amination), or Ullmann-type reactions to diversify the N‑aryl group while retaining the imide core.
• Medicinal chemistry utility (non-clinical):
  • The glutarimide ring is a privileged motif featured in discovery chemistry (e.g., as a conformationally restricted amide bioisostere). N‑(4‑chloro)phenyl variants provide a handle for further diversification.

Note: The above are literature-based use patterns for N‑aryl glutarimides and should be adapted to your substrate and scale.

Reaction Conditions

General literature guidance for N‑aryl glutarimide transformations (adapt to your substrate and scale):

• Enolate formation/alkylation:
  • Base: LDA or KHMDS (1.1–1.5 equiv) in THF or THF/THF–HMPA alternatives; −78 to 0 °C.
  • Electrophiles: primary alkyl bromides/iodides, benzyl halides, acyl chlorides (for acylation); quench at low temperature, then warm to rt.
  • Typical times: 0.5–2 h for deprotonation; 1–4 h for trapping; workup by aqueous NH4Cl and extraction.
• Cross-coupling on the aryl chloride:
  • Suzuki–Miyaura: Pd(PPh3)4 or Pd-PEPPSI type catalysts (0.5–2 mol%), base K2CO3 or K3PO4, solvent dioxane/H2O, 60–100 °C, 2–12 h.
  • Buchwald–Hartwig amination: Pd2(dba)3/BINAP or BrettPhos precatalysts, NaOtBu as base in toluene/dioxane, 80–110 °C.
• Reductions of the imide:
  • NaBH4 + BF3·Et2O or LiBH4 can give partial/complete reductions; monitor closely (0–25 °C) to avoid overreduction; yields are substrate dependent.
• Hydrolysis/ring opening:
  • Acidic: refluxing mineral acid (e.g., 6 M HCl) can induce opening over hours to days.
  • Basic: aqueous NaOH (2–6 M), reflux; N‑aryl imides are more resistant than N‑alkyl analogs.

Notes:

• Dry, oxygen-free conditions improve outcomes for strong-base chemistry.
• For scale-up, favor safer solvents (2‑MeTHF, CPME) where compatible, and optimize ligand/base to minimize Pd loadings in couplings.
• Expected yields vary widely by substrate and conditions; consult primary literature for close analogs.

Safety and Handling

Authoritative safety information must be taken from the SDS. The following are general considerations for N‑aryl cyclic imides:

• GHS classification, signal word, pictograms, H‑statements: Not specified for this item; refer to SDS.
• Likely hazards (general): may cause skin/eye irritation; dust may irritate respiratory tract. Avoid inhalation of powders and contact with eyes/skin.
• Personal protective equipment (typical lab practice):
  • Lab coat, safety glasses or splash goggles, and suitable chemically resistant gloves (e.g., nitrile).
  • Handle powders in a fume hood or with local exhaust to minimize dust exposure.
• Incompatibilities (general): strong bases/acids (can promote imide hydrolysis or ring opening), strong reducing agents (may attack carbonyls), strong oxidizers (aromatic oxidation risk). Avoid moisture for long-term stability, though many imides are hydrolytically robust under neutral conditions.
• First-aid overview (general):
  • Inhalation: move to fresh air; seek medical advice if symptoms persist.
  • Skin/eye contact: rinse with water for several minutes; remove contaminated clothing; seek medical attention if irritation develops.
  • Ingestion: rinse mouth; do not induce vomiting; obtain medical attention.
• Fire safety: Organic solid; use CO2, dry chemical, or foam. Combustion can produce CO/CO2, HCl from chloroarene.
• Waste disposal: Dispose of in accordance with institutional and local regulations; avoid release to the environment.

Always defer to the product SDS for definitive hazard classification and response measures.

Solvent Selection

This is a solid building block/intermediate rather than a process solvent. Solvent choice pertains to dissolving it for reactions, analytics, or stock solutions.

• Polarity class: moderately polar, aprotic aromatic imide (general characterization).
• Miscibility/solubility (literature/general):
  • Good: DMSO, DMF, NMP; often soluble in acetone and ethyl acetate.
  • Moderate: dichloromethane, acetonitrile, THF (warming/sonication may help).
  • Poor: water, aliphatic hydrocarbons, alcohols with low polarity.
• Practical selection guidance:
  • For reaction media and stock solutions: DMSO or DMF provide highest solubility and stability for imides; consider ACN or acetone when lower boiling point is needed.
  • For chromatographic workup: ethyl acetate/hexanes gradients or DCM/MeOH systems often separate N‑aryl imides cleanly.
  • For crystallization: ethanol/ethyl acetate or acetone/water antisolvent systems can be explored (screen required).
• Comparison (general):
  • DMSO vs DMF: DMSO highest solvating power but more challenging to remove; DMF better for amide couplings; both high‑bp.
  • ACN vs acetone: ACN offers lower proticity and UV transparency; acetone evaporates faster and often dissolves imides adequately.

Storage and Reconstitution

• Storage conditions (from Product Data): Room temperature.
• Container: Store tightly closed in a dry, well‑ventilated place; protect from prolonged humidity and light. Use original container or amber glass if long-term storage is anticipated.
• Stability: Imides are generally stable under neutral, dry conditions. Avoid strong acids/bases and reducing agents during storage.
• Reconstitution/stock solutions (general guidance):
  • Prepare concentrated stocks in DMSO, DMF, or acetonitrile, based on solubility screening. Filter (0.2 µm PTFE) if particulates are present.
  • For biochemical assays, add DMSO stocks to buffer with vigorous mixing to avoid precipitation; keep final DMSO below assay tolerance (commonly ≤1–2%).
  • Store organic stocks at −20 °C for extended periods; allow to warm to rt before opening to minimize moisture uptake. Avoid repeated freeze–thaw by aliquoting.

Research Use Note: For research use only.

Structure and Identity

Brief description: N-(4-Chlorophenyl)glutarimide is a cyclic imide (piperidine-2,6-dione core) bearing an N‑aryl substituent (para‑chloro phenyl). The scaffold is a 6‑membered ring with two opposing imide carbonyls and an anilide-type N–aryl linkage.

• Item-specific IDs (from Product Data):
  • CAS: 81305-70-6
  • CID: 2732366
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula (literature/computed): C11H10ClNO2
• Molecular weight (literature/computed): ~223.65 g/mol
• SMILES (literature/computed): O=C1N(c2ccc(Cl)cc2)C(=O)CCC1
• Core functional groups (general description):
  • Cyclic imide (piperidine-2,6-dione)
  • N-aryl anilide linkage (para-chloro substituent)
  • Two carbonyls enabling enolization at C-3 (between carbonyls)
• 2D structure in words: a six‑membered lactam–lactam ring (positions 2 and 6 carbonyl) with the ring nitrogen bonded to a 4‑chlorophenyl ring; the aromatic ring is para‑chlorinated, otherwise unsubstituted.
• Stereochemistry: achiral; no stereogenic centers expected.

Synthetic Utility

Key functional elements and their reactivity (general/literature):

• 1,3‑Dicarbonyl equivalent: The imide carbonyl pair stabilizes enolates at C‑3, enabling:
  • Alkylation (primary halides, tosylates), acylation (acid chlorides/anhydrides), and conjugate additions (Michael acceptors) under strong base (e.g., LDA, NaH, KHMDS).
• N‑Aryl vector with para‑chloro handle:
  • Pd‑catalyzed Suzuki–Miyaura to install diverse aryl/heteroaryl groups.
  • Buchwald–Hartwig amination to replace the aryl chloride with amines, generating N‑(4‑aminophenyl) variants or further derivatization.
• Carbonyl chemistry:
  • Selective reduction to hemiaminal/lactam derivatives (e.g., NaBH4 with Lewis acids) or full ring opening under forcing conditions to diamide/linear products.
• Late-stage diversification:
  • Electrophilic aromatic substitution on the ring is deactivated by Cl; cross-coupling is generally preferred.
• Protecting group behavior:
  • The imide can act as an amide surrogate; under hydrolytic conditions it can be unmasked to corresponding linear amino acid derivatives.

Retrosynthetic value: Serves as a convergent node linking an aniline (4‑chloro) fragment to a glutarimide core; enables bidirectional diversification at the aromatic ring (via Cl) and the imide α‑position (via enolate chemistry).

Target Specificity

Not applicable. This product is a small‑molecule research chemical, not an antibody, enzyme, or biological probe with defined target specificity provided. No item-specific biological target information is supplied.