4'-Iodoacetophenone
[CAS# 13329-40-3]

Identification

• Classification: Chemical reagent >> Organic reagent >> Aromatic ketone
• Name: 4'-Iodoacetophenone
• Synonyms: 1-(4-Iodophenyl)ethanone
• Molecular Formula: C₈H₇IO
• Molecular Weight: 246.04
• CAS Registry Number: 13329-40-3
• EC Number: 236-372-8
• SMILES: CC(=O)C1=CC=C(C=C1)I

Properties

• Density: 1.7±0.1 g/cm³ Calc.^*
• Melting point: 82 - 84 °C (Expl.)
• Boiling point: 279.9±23.0 °C 760 mmHg (Calc.)^*
• Flash point: 123.1±22.6 °C (Calc.)^*
• Index of refraction: 1.604 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P271-P280-P302+P352-P304+P340-P305+P351+P338-P319-P321-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

4'-Iodoacetophenone, also known as para-iodoacetophenone or 1-(4-iodophenyl)ethanone, is a halogenated aromatic ketone with the molecular formula C8H7IO. This compound is part of the broader class of acetophenone derivatives, which consist of a phenyl group substituted with a carbonyl-containing ethyl group. In the specific case of 4'-iodoacetophenone, an iodine atom is located at the para (4') position of the phenyl ring relative to the carbonyl group. It appears as a crystalline solid and is typically light-sensitive, requiring storage in dark containers.

This compound holds considerable value in synthetic organic chemistry due to the reactivity of the iodo substituent, which facilitates a wide range of coupling reactions. The carbon–iodine bond is particularly useful in palladium-catalyzed cross-coupling reactions such as Suzuki-Miyaura, Heck, and Sonogashira couplings. These reactions are crucial for constructing carbon–carbon bonds and are widely used in the synthesis of pharmaceuticals, agrochemicals, and organic materials. The high reactivity of the iodine atom in these transformations allows for efficient modification of the aromatic ring with various nucleophilic or organometallic partners.

4'-Iodoacetophenone has been employed as a starting material in the synthesis of more complex aromatic ketones, chalcones, and heterocyclic compounds. The carbonyl group at the acetophenone moiety also participates in diverse organic reactions, including condensation, oxidation, and reduction processes. For example, it can undergo aldol condensation to form enones or react with hydrazines to yield hydrazones, which are useful intermediates in medicinal chemistry.

In pharmaceutical research, 4'-iodoacetophenone serves as a useful building block for synthesizing bioactive molecules, particularly those containing aryl ketone or aryl-alkyne frameworks. The para-substituted iodine atom makes it a key intermediate for the targeted functionalization of aromatic systems, contributing to the modular synthesis of kinase inhibitors, antimicrobial agents, and imaging probes. Due to the presence of the iodine atom, derivatives of 4'-iodoacetophenone are also explored in radiolabeling studies involving iodine-125 or iodine-131 isotopes, useful in radiopharmaceutical development for diagnostic imaging and cancer treatment.

In materials science, the versatility of 4'-iodoacetophenone supports its use in creating functional organic compounds for electronic applications. Through its incorporation into conjugated systems, it can influence electron distribution and participate in the synthesis of light-emitting diodes, liquid crystals, and semiconducting polymers.

Synthesis of 4'-iodoacetophenone can be achieved through the electrophilic iodination of acetophenone using molecular iodine (I2) in the presence of an oxidizing agent or acid catalyst to ensure regioselectivity at the para position. This method is efficient and commonly used in laboratory settings. Purification is typically accomplished via recrystallization or chromatography, depending on the scale and desired purity.

Safety handling of 4'-iodoacetophenone includes the use of protective gloves, goggles, and fume hoods, as halogenated aromatics may pose risks such as skin irritation or organ toxicity upon prolonged exposure. It should be stored in a cool, dry, and light-protected environment to maintain its stability.

Overall, 4'-iodoacetophenone is a versatile and valuable compound in modern synthetic chemistry, supporting applications in drug discovery, materials design, and molecular engineering. Its dual functionality—offering both a reactive iodo substituent and a carbonyl group—makes it an ideal substrate for multi-step organic transformations.

References

1999. The crystal structure of 4-iodoacetophenone azine. Journal of Chemical Crystallography, 29(9).
DOI: 10.1023/a:1009581018860

2000. Near-perfect dipole parallel-alignment in the highly anisotropic crystal structure of 4-iodoacetophenone-(4-methoxyphenylethylidene) hydrazone. Journal of Chemical Crystallography, 30(7).
DOI: 10.1023/a:1011311918880

2001. Voltammetric Reductions of Ring-Substituted Acetophenones. 1. Determination of an Electron-Transfer Mechanism Using Cyclic Voltammetry and Computer Modeling: The Formation and Fate of a Radical Anion. The Chemical Educator, 6(6).
DOI: 10.1007/s00897010522a