3-Propylidenephthalide
[CAS# 17369-59-4]

Identification

• Classification: Flavors and spices >> Synthetic spice >> Lactone and oxygen-containing heterocyclic compound >> Furan and pyran
• Name: 3-Propylidenephthalide
• Synonyms: (3Z)-3-propylidene-2-benzofuran-1-one
• Molecular Formula: C₁₁H₁₀O₂
• Molecular Weight: 174.20
• CAS Registry Number: 17369-59-4
• EC Number: 241-402-8
• FEMA: 2952
• SMILES: CC/C=C\1/C2=CC=CC=C2C(=O)O1

Properties

• Solubility: 1087 mg/L (25 ºC water)
• Density: 1.2±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.651, Calc.^*
• Melting point: 66.78 ºC
• Boiling Point: 318.22 ºC, 298.0±33.0 ºC (760 mmHg), Calc.^*
• Flash Point: 121.2±22.8 ºC, Calc.^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H317
• Precautionary Statements: P261-P264-P270-P272-P280-P301+P312+P330-P302+P352-P333+P313-P363-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Skin sensitization	Skin Sens.	1	H317
Skin sensitization	Skin Sens.	1B	H317
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319

Discovory and Applicatios

3-Propylidenephthalide is an organic compound belonging to the class of phthalides, which are characterized by a fused lactone ring structure derived from isobenzofuranone. The molecular structure of 3-propylidenephthalide consists of a phthalide core substituted with a propylidene group at the 3-position. The compound is known for its occurrence in certain plant-derived essential oils and has been studied in the context of natural product chemistry.

The isolation of 3-propylidenephthalide from natural sources was reported in studies examining the volatile constituents of various aromatic plants. It has been identified in species such as *Levisticum officinale* (lovage), where it contributes to the characteristic odor profile of the plant. Analytical techniques including gas chromatography (GC) and gas chromatography–mass spectrometry (GC–MS) were employed in the identification and quantification of 3-propylidenephthalide in essential oil extracts. The structure was confirmed through spectroscopic methods such as nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry.

The biosynthesis of 3-propylidenephthalide in plants involves the polyketide pathway, which is responsible for the formation of many aromatic and lactone-containing natural products. In the case of phthalides, the biosynthetic precursor is derived from or similar to o-coumaric acid or ferulic acid, and subsequent enzymatic cyclization and modification steps yield the lactone ring and side chain substitution patterns characteristic of this class of compounds.

In terms of chemical reactivity, 3-propylidenephthalide contains a conjugated system involving the lactone and the exocyclic double bond. This structural feature makes the compound amenable to certain electrophilic and nucleophilic addition reactions, which are utilized in the derivatization of phthalide compounds. Laboratory synthesis of 3-propylidenephthalide and its analogs has been achieved through established synthetic routes, typically starting from phthalic anhydride or substituted cinnamic acid derivatives, followed by cyclization and alkylidene introduction.

Applications of 3-propylidenephthalide have primarily been explored in the context of flavor and fragrance chemistry. Due to its aromatic properties and presence in culinary herbs such as lovage, it is considered a contributor to the sensory qualities of food products and essential oils. It has been evaluated as a flavoring ingredient, and its olfactory properties have been characterized in sensory studies. The compound exhibits a warm, celery-like aroma, which aligns with its natural origin and supports its use in flavor formulation.

In addition to its role in flavor chemistry, 3-propylidenephthalide has been the subject of studies in pharmacognosy and natural product research. Some research has investigated the bioactivity of phthalide derivatives, including their antioxidant and antimicrobial properties. However, such biological studies generally involve broader classes of related compounds, and conclusions are drawn based on comparative analysis of structural features. The role of 3-propylidenephthalide in these contexts is documented through its inclusion in compound libraries used for screening assays.

Further analytical studies have used 3-propylidenephthalide as a marker compound in the quality control of herbal preparations and essential oils. Its presence and concentration can serve as indicators of plant authenticity and processing conditions. Standard methods such as GC–MS remain the primary tools for its detection and quantification in complex plant matrices.

3-Propylidenephthalide remains a compound of interest due to its natural occurrence, role in the sensory characteristics of plant materials, and potential as a structural component in further chemical studies. Its identification in essential oils and its significance in flavor chemistry are well-established in the scientific literature.

References

2021. RIFM fragrance ingredient safety assessment, 3-propylidenephthalide, CAS Registry Number 17369-59-4. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 155.
DOI: 10.1016/j.fct.2021.112490

2021. Allergen fragrance molecules: a potential relief for COVID-19. BMC Complementary Medicine and Therapies, 21(1).
DOI: 10.1186/s12906-021-03214-4

2007. Synthesis, resolution, and antiplatelet activity of 3-substituted 1(3H)-isobenzofuranone. Bioorganic & Medicinal Chemistry Letters, 17(18).
DOI: 10.1016/j.bmcl.2007.06.082