Ethyl cis-3-Iodoacrylate 31930-36-6 98% Colorless to Pale Yellow Liquid Vinyl Iodide Ester / Organic Synthesis Intermediate

1. Product Overview

Ethyl cis-3-Iodoacrylate (CAS 31930-36-6), also known as (Z)-ethyl 3-iodoacrylate or cis-3-iodoacrylic acid ethyl ester, is a Z-configured vinyl iodide ester. It is prepared from ethyl propiolate via sodium iodide addition and features a reactive C=C double bond with Z-iodine substituent and an ester group, making it a versatile synthon for transition-metal-catalyzed cross-coupling reactions (Suzuki, Stille, Heck), cyclopropanation, and the construction of complex naphtho(benzo)furans. The compound is typically stabilized with a copper chip to prevent premature polymerization or decomposition and is widely used in pharmaceutical intermediate synthesis, materials science, and chemical biology probe development.

2. Key Features and Benefits

• Z-Stereoselectivity: The cis (Z) configuration is locked during synthesis, providing a defined stereochemical starting point for stereoselective transformations and cyclizations.

• Reactive Vinyl Iodide Moiety: The C(sp²)–I bond participates readily in Pd-catalyzed cross-couplings (Suzuki-Miyaura, Stille, Heck) with boronic acids, stannanes, and olefins, enabling rapid molecular diversification.

• Stabilized Formulation: Supplied with a copper chip (Cu) to inhibit radical-mediated polymerization and iodine extrusion, ensuring consistent reactivity over shelf life.

• Ester Handle: The ethyl ester can be hydrolyzed to the carboxylic acid or transesterified, providing access to further derivatization (amide coupling, reduction to alcohol, etc.).

• Proven in Complex Synthesis: Documented in the synthesis of fused naphthofurans, cobalt-catalyzed cross-couplings with functionalized organozinc pivalates, and covalent inhibitor design targeting cysteine proteases.

3. Major Applications

• Transition Metal-Catalyzed Cross-Coupling: Used as a vinyl iodide partner in Suzuki-Miyaura, Stille, and Heck reactions to construct substituted alkenes, dienes, and aromatic systems.

• Heterocycle Synthesis: Employed in the preparation of complex naphtho(benzo)furans and other oxygen-containing fused heterocycles via cyclization strategies.

• Organometallic Chemistry: Serves as a substrate in cobalt-catalyzed cross-coupling of functionalized organozinc pivalates, enabling the introduction of diverse functional groups.

• Covalent Inhibitor / Chemical Biology Probes: The iodoacrylate Michael acceptor moiety can form covalent adducts with cysteine residues in target proteins (e.g., SARS-CoV-2 main protease), serving as a warhead in irreversible inhibitor design.

• Prodrug & Bioavailability Enhancement: Incorporated into prodrug scaffolds to improve membrane permeability and control release profiles.

• Materials Science: Used in the synthesis of functional acrylate-based polymers and organic electronic materials.

4. Technical Specifications

Item Description
Product Name Ethyl cis-3-Iodoacrylate (stabilized with Copper chip)
Synonyms (Z)-Ethyl 3-iodoacrylate; cis-3-Iodoacrylic acid ethyl ester; Ethyl cis-3-iodoacrylate; Ethyl (2Z)-3-iodoprop-2-enoate
CAS Number 31930-36-6
Molecular Formula C₅H₇IO₂
Molecular Weight 226.01 g/mol
MDL Number MFCD00209584
Reaxys Registry 1902819
PubChem SID 87571851
Assay (Purity) ≥95% / ≥98% (GC)
Physical State (20 °C) Colorless to pale yellow transparent liquid
Appearance Clear, light yellow liquid
Boiling Point 85 °C @ 20 mmHg (Literature)
Flash Point 99 °C / 210 °F
Density 1.765 g/mL at 25 °C (Literature)
Refractive Index n²⁰/D = 1.533 (Literature)
Vapor Pressure ~0.359 mmHg at 25 °C
Solubility Soluble: Chloroform (CHCl₃), Dichloromethane (DCM), Ethyl acetate (slightly), THF, Acetone, Acetic acid.
Insoluble:Water (practically insoluble).
Spectral Data ¹H NMR (CDCl₃, 400 MHz): δ 1.30 (t, J≈7.1 Hz, 3H, OCH₂CH₃), 4.20 (q, J≈7.1 Hz, 2H, OCH₂CH₃), 5.85 (d, J≈8.0 Hz, 1H, =CH–COOEt), 7.15 (d, J≈8.0 Hz, 1H, =CH–I).
¹³C NMR (CDCl₃):δ 14.0 (OCH₂CH₃), 60.5 (OCH₂CH₃), 95.5 (C–I), 130.0 (=CH–COO), 143.5 (=CH–I), 165.0 (C=O).
SMILES CCOC(=O)/C=C\I
InChI Key AELYFQSZXFFNGP-ARJAWSKDSA-N
Storage Refrigerated (0–10 °C), under inert gas (N₂/Ar), protected from light
Stabilizer Copper chip (Cu)
Sensitivity Light-sensitive, Air-sensitive, Heat-sensitive
HS Code 2916.19.00 / 2918.99.90

5. Storage and Handling

• Storage: Store refrigerated at 0–10 °C (ideally 2–8 °C) under an inert atmosphere (N₂ or Ar), protected from light. The copper chip stabilizer should remain in the container to prevent decomposition. Stable for ≥12–18 months under these conditions.

• Handling: Allow the sealed container to warm to room temperature in a dark environment before opening to prevent condensation and minimize light exposure. Handle quickly in a fume hood with minimal light exposure.

• Solution Preparation: Dilute in anhydrous CHCl₃, DCM, THF, or EtOAc immediately before use. Avoid protic solvents (MeOH, H₂O) which may hydrolyze the ester or promote HI elimination. Protect from light during all operations.

• Polymerization Risk: The vinyl iodide can undergo radical polymerization if exposed to light, heat, or trace peroxides. The copper chip mitigates this; do not remove until immediately before use.

• Freeze-Thaw: Not applicable (liquid at RT); however, repeated warming/cooling cycles should be minimized.

6. Safety Summary (Full SDS Highlights)

• GHS Classification: GHS07 – Warning

• Signal Word: Warning

• Hazard Statements:

• H315: Causes skin irritation.

• H319: Causes serious eye irritation.

• H335: May cause respiratory irritation.

• Precautionary Statements:

• P261: Avoid breathing vapor/mist. Use only in a well-ventilated area or fume hood.

• P264: Wash hands, forearms, and face thoroughly after handling.

• P270: Do not eat, drink, or smoke in areas where this material is used.

• P271: Use only outdoors or in a well-ventilated area.

• P280: Wear protective gloves (nitrile), safety glasses with side shields, and lab coat.

• P301+P312: IF SWALLOWED: Call a POISON CENTER or physician if you feel unwell.

• P302+P352: IF ON SKIN: Wash with plenty of soap and water.

• P304+P340: IF INHALED: Remove person to fresh air and keep comfortable for breathing.

• P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present and easy to do. Continue rinsing.

• P330: Rinse mouth if swallowed.

• P337+P313: If eye irritation persists: Get medical advice/attention.

• P403+P233: Store in a well-ventilated place. Keep container tightly closed.

• P501: Dispose of contents/container in accordance with local, regional, and national regulations.

• First Aid Measures:

• Inhalation: Remove to fresh air. If breathing difficult, administer oxygen and seek medical attention.

• Skin Contact: Immediately wash with plenty of soap and water. Remove contaminated clothing. Seek medical advice if irritation or rash develops.

• Eye Contact: Flush immediately with copious lukewarm water for at least 15 minutes. Remove contact lenses if possible. Seek medical attention.

• Ingestion: Rinse mouth. Do NOT induce vomiting. Give water to drink if conscious. Seek medical advice.

• Fire-Fighting Measures:

• Suitable Extinguishing Media: Water spray, alcohol-resistant foam, dry chemical, or CO₂.

• Special Hazards: Combustion may produce irritating/acrid smoke (HI, I₂ vapor, CO). Iodine vapors are toxic and corrosive.

• Protective Equipment: Wear self-contained breathing apparatus (SCBA) and full protective clothing.

• Spill Response:

• Absorb with inert material (sand, vermiculite). Do NOT use combustible materials. Prevent runoff from entering waterways. Ventilate area after cleanup. Place residue in sealed container for disposal.

• Handling & Storage:

• Handle in fume hood away from light. Keep container closed when not in use. Store refrigerated (0–10 °C), protected from light and air. Keep away from strong oxidizers, strong bases, and heat sources.

• Intended Use: For laboratory research and development ONLY. Not for human or veterinary therapeutic, diagnostic, or food use. Handle as a potentially hazardous chemical (iodine-containing organics may release HI upon decomposition).

Pls input...