Diethyl 2-[(2,5-dimethylanilino)methylene]malonate , CAS No.103976-09-6

CAS: 103976-09-6 Cat. No.: D996830 Formula: C₁₆H₂₁NO₄ Peso molecolare: 291.35 PubChem CID: 2728229

Storage

Room temperature

Specifications

Condizioni di conservazione di stoccaggio

Room temperature

Nomi e identificatori

Sorrisi canonici

CCOC(=O)C(=CNC1=C(C=CC(=C1)C)C)C(=O)OCC

IUPAC Name

diethyl 2-[(2,5-dimethylanilino)methylidene]propanedioate

InChIKey

SAXNLAREMLRWHN-UHFFFAOYSA-N

INCHI

1S/C16H21NO4/c1-5-20-15(18)13(16(19)21-6-2)10-17-14-9-11(3)7-8-12(14)4/h7-10,17H,5-6H2,1-4H3

Isomeri SMILES

CCOC(=O)C(=CNC1=C(C=CC(=C1)C)C)C(=O)OCC

PubChem CID

2728229

Peso molecolare

291.35

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Benzene and substituted derivatives
      • Subclass Xylenes

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Xylenes
• Intermediate Tree Nodes: Not available
• Direct Parent: p-Xylenes
• Alternative Parents: Aniline and substituted anilines Secondary alkylarylamines Dicarboxylic acids and derivatives Vinylogous amides Enoate esters Amino acids and derivatives Enamines Allylamines Organopnictogen compounds Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: P-xylene - Aniline or substituted anilines - Secondary aliphatic/aromatic amine - Dicarboxylic acid or derivatives - Enoate ester - Alpha,beta-unsaturated carboxylic ester - Vinylogous amide - Amino acid or derivatives - Carboxylic acid ester - Carboxylic acid derivative - Enamine - Secondary amine - Allylamine - Organooxygen compound - Organonitrogen compound - Organic nitrogen compound - Organopnictogen compound - Organic oxygen compound - Amine - Organic oxide - Carbonyl group - Hydrocarbon derivative - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as p-xylenes. These are aromatic compounds that contain a p-xylene moiety, which is a monocyclic benzene carrying exactly two methyl groups at the 1- and 4-positions.
• 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: 291.340 g/mol
• XLogP3: 4.000
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 8
• Exact Mass: 291.147 Da
• Monoisotopic Mass: 291.147 Da
• Topological Polar Surface Area: 64.599 Ų
• Heavy Atom Count: 21
• Formal Charge: 0
• Complexity: 372.000
• 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 application protocols are specified for this item. As a synthetic building block, procedures are reaction-specific. For guidance, see the Reaction Conditions and Synthetic Utility sections and consult primary literature for substrate- and catalyst-dependent parameters. Research Use Only.

Biological Roles

This product is a synthetic organic building block and is not intended for biological use beyond research and discovery chemistry.

General context (literature; not product-specific):

• β-Enamino diesters are occasionally used as precursors to heterocycles that are evaluated in medicinal chemistry programs (e.g., pyridines, pyrimidinones, pyrazoles). Any biological activity stems from the downstream scaffolds rather than the starting enaminomalonate itself.
• The 2,5-dimethyl anilide increases lipophilicity and may influence physicochemical properties (e.g., cLogP) of intermediates during library synthesis, but it does not confer a defined biological role.

No endogenous metabolic or signaling function is associated with this compound. For laboratory safety and environmental fate, consult the SDS and local regulations. Research Use Only.

Buffer Applications

Not typically applicable. This compound is a hydrophobic organic reagent, not a buffering agent. It lacks conjugate acid/base pairs with appropriate aqueous pKa and solubility for preparing laboratory buffers. For practical use information, refer instead to the Reaction & Applications, Synthetic Utility, and Solvent Selection sections.

Green Alternatives

Opportunities to increase sustainability when working with anilino-methylene malonates center on solvent choice, activation mode, and workup.

Greener solvent substitutions (general guidance):

• Replace chlorinated solvents (DCM/CHCl3) with 2-MeTHF or ethyl acetate where solubility and rate permit.
• Use acetonitrile instead of DMF/DMSO to ease removal and reduce EHS burden, provided reactivity is maintained.
• Employ toluene or 2-MeTHF for higher-temperature reflux in place of xylene.

Comparison (literature-based, general):

• DCM vs 2-MeTHF: similar solvency for enamino diesters; 2-MeTHF is biorenewable and has lower toxicity, but offers slightly lower polarity which can slow some condensations.
• DMF vs MeCN: DMF enhances solubility of polar partners but is problematic in waste streams; MeCN is volatile and easier to recycle but flammable.

Process and energy:

• Catalysis: adopt Lewis/Brønsted acid catalysis at low loadings or organocatalysis to reduce stoichiometric promoters.
• Solvent-free or mechanochemical approaches: for some condensations and Michael additions, neat milling or melt-phase methods have been reported to reduce solvent use (literature, case-dependent).
• Workup: prefer aqueous bicarbonate quench and phase separation over column chromatography when impurity profile allows; use minimal silica and greener eluents (heptane/EtOAc).

Note: These are general green-chemistry suggestions; verify feasibility and performance for this specific substrate.

Pharmaceutical Uses

No pharmacopeial/excipient status is indicated for this item. It is supplied for research use only as a synthetic intermediate.

General formulation/manufacturing context (literature; not product-specific):

• Enaminomalonates serve as versatile intermediates en route to heteroaromatic scaffolds that may be screened in drug discovery. They are not typically used directly in finished dosage forms.
• If incorporated into process R&D, control of residual aromatic amines and malonate derivatives is important for regulatory toxicology. Validate purge of aniline-related impurities during downstream steps.

Item-specific note: Grade/purity and any compendial compliance are not specified for this item; refer to CoA/Spec Sheet if required for GMP feasibility assessments.

Physical Properties

Item-specific specifications (this product):

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• Melting/boiling points, density, refractive index, UV cutoff, water/peroxide/metal limits: Not specified for this item; refer to CoA/Spec Sheet.

General/literature expectations for anilino-methylene malonates (informational only; not product specifications):

• Physical state: typically low-melting solids or viscous oils; color often pale yellow to orange due to extended conjugation.
• Solubility: good solubility in common organic solvents (e.g., dichloromethane, chloroform, ethyl acetate, THF, toluene, acetonitrile); limited solubility in water.
• Polarity/logP: moderately lipophilic owing to two ethyl esters and an aryl group; logP expected in the mid-range for aromatic diesters (literature, qualitative).
• Spectroscopic handles: strong IR C=O absorptions (~1730–1700 cm⁻¹ for esters) and C=C/N–H bands; 1H NMR shows vinylic CH (downfield), NH (exchangeable), aromatic protons, benzylic methyl singlets, ethyl quartet/triplet patterns; 13C NMR displays two carbonyl carbons and vinylic/aromatic carbons.

Notes for use:

• Moisture sensitivity: enaminomalonates can undergo slow hydrolysis or isomerization; handle under dry conditions for reproducibility (general best practice).

Quality and Grades

Item-specific information:

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

Guidance for interpreting grades (general):

• Research grade: suitable for most synthetic and screening workflows; actual assay and impurity profile should be verified via CoA.
• Analytical/HPLC grade (if applicable): tighter control of volatile/non-volatile impurities and lower UV background; advantageous for photometric detections or when used as reference standards.
• Water and trace metals: for moisture- or metal-sensitive reactions, verify water (Karl Fischer) and elemental impurities if the chemistry demands it. If not listed, request a detailed specification.

Practical quality notes for enaminomalonates (general):

• Isomer content (E/Z): can influence NMR and reactivity. High-purity material typically shows a dominant geometric isomer; confirm by NMR/LC as needed.
• Residual aniline or malonate: common process-related impurities; easy to detect by GC/LC. A brief vacuum strip or triturations can reduce volatiles.
• Color and stability: mild yellowing does not necessarily indicate degradation; monitor by HPLC assay and 1H NMR for hydrolysis (appearance of CH2 at C-2 of malonate) or transamination byproducts.

Reaction and Applications

This compound is a representative anilino-methylene malonate (β-enamino diester), a versatile electrophilic synthon leveraging conjugation with two ester groups and a vinylogous amide. It participates in numerous C–C and C–N bond-forming reactions.

Representative application classes (literature/general):

• Cyclocondensations with 1,2- and 1,3-dinucleophiles to access heterocycles (e.g., pyrazoles from hydrazines, pyrimidinones from urea/thiourea/guanidine, dihydropyridines/pyridines via Hantzsch-type variants using 1,3-dicarbonyl partners).
• Conjugate additions/Michael-type reactions where soft nucleophiles add across the activated C=C, followed by proton transfer and, in some cases, displacement of the anilide under forcing or catalytic conditions.
• Transamination/exchange: the anilide can be replaced by aliphatic amines to furnish dialkylaminomethylene malonates, which are prized as push–pull enamine donors.
• Knoevenagel/Mannich manifolds: as a stabilized donor–acceptor alkene engaged by iminium or enamine catalysis in C–C couplings.

Practical tips:

• Maintain anhydrous conditions to minimize hydrolysis back to diethyl malonate.
• Weak base (e.g., Et3N) or Lewis acids (e.g., ZnCl2, InCl3) can accelerate condensations; Brønsted acids can activate the anilide as a leaving group in cyclizations.
• The 2,5-dimethyl substitution increases steric hindrance at nitrogen, often enhancing chemoselectivity in conjugate addition vs N-acylation, and can influence E/Z ratio.
• Monitor reactions by LC/MS; characteristic UV absorption around 300–350 nm (conjugated system; literature) aids tracking.

Reaction Conditions

General literature guidance for β-enamino diester chemistry (not product specifications):

• Cyclocondensation to pyrazoles:

  • Reagents: hydrazine or substituted hydrazines (1.0–1.5 eq)
  • Solvent: ethanol, acetic acid, or acetonitrile
  • Conditions: 25–80 °C, 1–6 h; catalytic acid (AcOH) can accelerate
  • Notes: monitor by LC/MS; N–N addition across C=C followed by cyclization and proton transfers

• Formation of (thio)pyrimidinones (with urea/thiourea/guanidine):

  • Solvent: EtOH, MeCN, or solvent-free melt
  • Catalyst: Brønsted acid (e.g., p-TsOH) or Lewis acid (ZnCl2, InCl3, FeCl3; 5–10 mol%)
  • Conditions: 60–100 °C, 2–12 h

• Transamination to dialkylaminomethylene malonates:

  • Nucleophile: secondary amine (e.g., morpholine, piperidine; 1.2–2.0 eq)
  • Solvent: toluene, MeCN, or neat
  • Conditions: 60–120 °C; removal of aniline byproduct drives equilibrium; optional acid scavenger (Et3N)

• Michael additions (C-nucleophiles):

  • Nucleophiles: malonates, nitroalkanes, β-dicarbonyls
  • Base: mild (Et3N, DBU, K2CO3)
  • Solvent: MeCN, DCM, or 2-MeTHF
  • Temperature: 0–25 °C (controlled) to limit side reactions

Typical outcome: moderate to high conversions (literature), contingent on nucleophile strength and sterics. Always optimize stoichiometry, temperature, and catalyst loading for the specific substrate pairing.

Safety and Handling

Item-specific hazard data:

• GHS classification, signal word, pictograms, H-statements: Not specified for this item; refer to SDS.

General laboratory safety guidance for β-enamino diesters and aromatic amines (informational; defer to SDS for this product):

• Potential hazards: may cause skin/eye irritation and respiratory irritation; aromatic anilide fragments can be harmful if ingested or absorbed. Avoid inhalation of vapors/aerosols and contact with skin/eyes.
• PPE: wear lab coat, safety glasses or face shield, and appropriate chemical-resistant gloves (e.g., nitrile). Use in a fume hood.
• Storage incompatibilities: avoid strong acids/bases (can catalyze hydrolysis/transamination), strong oxidizers, and moisture. Keep container tightly closed.
• Handling tips: minimize exposure to air and humidity; dispense with dry glassware. Clean up small spills with inert absorbent; prevent material from entering drains.
• First aid (overview; consult SDS):
  • Inhalation: move to fresh air; seek medical attention if symptoms persist.
  • 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; seek medical advice if irritation continues.
  • Ingestion: rinse mouth; do not induce vomiting; seek medical advice.
• Fire safety: many organic enamines/esters are combustible. Use CO2, dry chemical, or foam. Combustion may produce CO/CO2 and nitrogen oxides.

Solvent Selection

This substance is a moderately polar, conjugated diester bearing an anilide. It dissolves well in many organic solvents used in synthesis and cyclocondensation chemistry.

General solvent compatibility (literature-based):

• Highly suitable: dichloromethane, chloroform, ethyl acetate, THF, acetonitrile, toluene, DMF, DMSO.
• Limited: alcohols (risk of transesterification under acidic/basic conditions); water (poor solubility).

Selection guidance:

• Electrophilic/cyclocondensation reactions (e.g., with N–N or N–C–N 1,3-dinucleophiles): choose polar aprotic media (MeCN, DMF, DMSO) to enhance rates; add mild base (e.g., Et3N) or acid catalysis depending on mechanism.
• Conjugate additions/Mannich-type couplings: chlorinated solvents or MeCN balance solubility and stability; keep moisture low.
• Workup/extraction: ethyl acetate/hexanes partitions well; avoid basic aqueous washes that might induce hydrolysis.

Small comparison (general):

• DCM vs. toluene: DCM gives faster kinetics for polar transition states; toluene offers higher boiling point for reflux-driven condensations.
• MeCN vs. DMF: MeCN is easier to remove and more benign; DMF improves solubility for polar partners but complicates workup.
• 2-MeTHF/EtOAc: greener options that often dissolve enamino diesters adequately for many condensations.

Storage and Reconstitution

Item-specific storage:

• Storage Conditions: Room temperature (Product Data).
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

General handling and stability notes for enaminomalonates:

• Keep container tightly closed in a dry, well-ventilated place. Protect from moisture and strong acids/bases to prevent hydrolysis or transesterification.
• If long-term storage is anticipated, consider storing under inert gas and in amber glass to limit oxidative discoloration and UV exposure (general best practice).
• Reconstitution: solid or viscous materials typically dissolve readily in DCM, EtOAc, MeCN, THF, or toluene. Prepare stock solutions using anhydrous solvents; filter if needed through PTFE syringe filters.
• Freeze–thaw: not generally required. If solutions are prepared, store aliquots to avoid repeated freeze–thaw cycles that can introduce moisture.

Research Use Only: This material is for laboratory research and development. Consult the SDS for detailed stability, incompatibilities, and spill/first-aid procedures.

Structure and Identity

Diethyl 2-[(2,5-dimethylanilino)methylene]malonate is a β-enamino diester derived from diethyl malonate and 2,5-dimethylaniline. It features a conjugated C=C–N(H) motif flanked by two ethyl ester groups and a 2,5-dimethyl-substituted anilide.

• CAS: 103976-09-6 (item-specific, Product Data)
• PubChem CID: 2728229 (item-specific, Product Data)
• InChIKey: 331230 (item-specific, 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.

Structural features (general/literature description):

• Core scaffold: diethyl malonate (two ethyl ester groups, –CO2Et) conjugated through a methine (–CH=) to an anilido nitrogen (–NH–Ar), giving a β-enamino diester.
• Aromatic ring: aniline ring substituted with methyl groups at the 2- and 5-positions (ortho and meta to –NH–), increasing lipophilicity and steric bias around the enamine.
• Functional groups: vinylogous amide (enamine), two ester carbonyls, secondary anilide N–H, and two benzylic methyl substituents.
• 2D description: an approximately planar enaminomalonate fragment (O=CO–CH=C–N(H)–) conjugated to a 2,5-dimethylphenyl ring; ethyl groups extend from each carbonyl as flexible alkyl chains.
• Stereochemistry: the C=C (enamine) may exist as E/Z geometrical isomers (literature), with the E-form commonly favored due to minimized steric clash between the anilide and ester substituents.

Synthetic Utility

Functional group reactivity (general literature for anilino-methylene malonates):

• Vinylogous amide (enamine) adjacent to a 1,3-dicarbonyl equivalent (malonate) makes a polarized C=C bond activated toward nucleophilic addition (Michael-type) and cyclocondensation.
• The anilide nitrogen can serve as a leaving group under acidic or thermal conditions, enabling substitution by heteroatom nucleophiles (transamination) to generate dialkylamino-methylene malonates.
• Two ester handles allow downstream diversification: decarboxylation, saponification/ester exchange, or conversion to amides and acids.

Named/typical transformations:

• Hantzsch-like annulations to dihydropyridines/pyridines using ammonia/amine sources and 1,3-dicarbonyl partners.
• Condensations with hydrazines to furnish pyrazoles; with urea/thiourea/guanidine to give (thio)pyrimidinones.
• Mannich/Knoevenagel-type couplings under Lewis acid or organocatalytic activation.

Retrosynthetic value:

• Acts as a masked malonate synthon where the enamine polarity templates regioselective bond construction at the α,β-unsaturated site before unveiling carboxylate functions.

Orthogonal selectivity considerations:

• 2,5-Dimethyl anilide increases steric protection at nitrogen, often favoring C–C bond formation over competing N-acylation; methyl groups can modulate electronics, subtly affecting rate and product distribution.

Target Specificity

Not applicable. This product is a small-molecule synthetic reagent and is not an antibody, probe, or biologic. No antigen/epitope specificity, clone, or isotype information applies.