120-57-0

Basic information

• Product Name: Piperonyl aldehyde
• Synonyms: HELIOTHROPINE;HELIOTROPIN;HELIOTROPINE;FEMA 2911;LABOTEST-BB LT00933538;3,4-(METHYLENEDIOXY)BENZALDEHYDE;1,3-BENZODIOXOLE-5-CARBOXALDEHYDE;TIMTEC-BB SBB007752
• CAS NO: 120-57-0
• Molecular Formula: C₈H₆O₃
• Molecular Weight: 150.13
• EINECS: 204-409-7
• Product Categories: Food and Feed Additive;Aldehydes;Building Blocks;C8;Carbonyl Compounds;Chemical Synthesis;Organic Building Blocks
• Mol File: 120-57-0.mol

Chemical Properties

• Melting Point: 35-39 °C(lit.)
• Boiling Point: 264 °C(lit.)
• Flash Point: >230 °F
• Appearance: white crystalline solid
• Density: 1.2645 (rough estimate)
• Vapor Pressure: 1 mm Hg ( 87 °C)
• Refractive Index: 1.4500 (estimate)
• Storage Temp.: Dark Room
• Solubility: methanol: 0.1 g/mL, clear
• Water Solubility: Slightly soluble
• Sensitive: Air & Light Sensitive
• Stability: Stable, but air and light sensitive. Combustible. Incompatible with strong oxidizing agents, bases.
• Merck: 13,7556
• BRN: 131691
• CAS DataBase Reference: Piperonyl aldehyde(CAS DataBase Reference)
• NIST Chemistry Reference: Piperonyl aldehyde(120-57-0)
• EPA Substance Registry System: Piperonyl aldehyde(120-57-0)

Safety Data

• Hazard Codes: Xi
• Statements: 38-52/53
• Safety Statements: 61-24/25
• WGK Germany: 2
• RTECS: TO1575000
• F: 8-10-23
• TSCA: Yes
• Hazardous Substances Data: 120-57-0(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Piperonal is used as an impurity of Tadalafil (T004500), specifically as Tadalafil impurity A. This application is important for the pharmaceutical industry as it helps in the development and quality control of Tadalafil, a medication used to treat erectile dysfunction and symptoms of benign prostatic hyperplasia.
Used in Perfumery and Flavor Industry:
Piperonal is used as a fragrance and flavoring agent in the perfumery and flavor industry. Its sweet, flowery odor and bittersweet taste make it a valuable component in creating various scents and flavors. It is used in cherry and vanilla flavors, contributing to the ripe black cherry, ripe berry, sweet, macaroon, Jordan almond, creamy vanilla, spicy cream soda, and slight floral with hay nuances.
Used in Organic Syntheses:
Piperonal is also utilized in organic syntheses, where it serves as a key intermediate or building block for the production of various chemicals and compounds. Its chemical properties, such as being a white crystalline solid with a sweet, floral, slightly spicy, heliotrope-like odor, make it a versatile compound for synthesis purposes.
Aroma threshold values for Piperonal are as follows:
Detection: 62 ppb to 1 ppm
Aroma characteristics at 1.0%: sweet, anise-like, almond vanilla, floral, black cherry pit, berry raspberry, powdery coumarin-like with a hint of hay.

Synthesis

Piperonyl alcohol (0.15 g, 1.00 mmol) was dissolved in EtOAc (7 mL, 0.14 M fifinal concentration), and 1-hydroxy-1,2,benziodoxol-3(1H)-one (IBX 0.84 g, 3.00 mmol) was added. The resulting suspension was immersed in an oil bath set to 80 °C and stirred vigorously open to the atmosphere. After 3.25 h (TLC monitoring), the reaction was cooled to room temperature and fifiltered through a medium glass frit. The fifilter cake was washed with 3 × 2 mL of EtOAc, and the combined fifiltrates were concentrated to yield 0.14 g (90%, > 95% pure by 1 H NMR) of piperonal as a waxy solid. Reference: More, J. D.; Finney, N. S. Org. Lett. 2002, 4, 3001?3003.

Synthesis

By the oxidation of isosafrole with potassium dichromate and sulfuric acid and subsequent steam distillation of piperonal

Preparation

Heliotropin is produced by two main routes:1) From isosafrole: For many years, oxidative cleavage of isosafrole was the only route applicable on an industrial scale. Isosafrole [120-58-1] is obtained by isomerization from safrole [94-59-7], which can be isolated from (Chinese) sassafras oil . Examples of oxidants that give good yields of heliotropin are chromium(VI) salts, oxygen, and ozone.This method is still used currently, but the destructive exploitation of sassafras trees in Southeast Asia has led to a strong decline in the availability of sassafras oil and thus of safrole/isosafrole.2) From catechol: Several routes have recently been developed for the synthesis of heliotropin from catechol. In one such route, catechol is converted into 3,4-dihydroxymandelic acid with glyoxylic acid in an alkaline medium in the presence of aluminum oxide. 3,4-Dihydroxymandelic acid is oxidized to the corresponding keto acid (e.g., with copper-(II) oxide), which is decarboxylated to 3,4-dihydroxybenzaldehyde. The latter product is converted into heliotropin, for example, by reactionwith methylene chloride in the presence of quaternary ammonium salts.In another route, catechol is first reacted with methylene chloride and converted into 1,2-methylenedioxybenzene . Reaction with glyoxylic acid in strongly acidic media yields 3,4-methylenedioxymandelic acid . Subsequent oxidation and decarboxylation with nitric acid afford heliotropin.Alternative routes that start from 1,2-methylenedioxybenzene and use piperonyl chloride as intermediate have been described .

Synthesis Reference(s)

Canadian Journal of Chemistry, 64, p. 225, 1986 DOI: 10.1139/v86-039The Journal of Organic Chemistry, 48, p. 4053, 1983 DOI: 10.1021/jo00170a036Tetrahedron Letters, 33, p. 5909, 1992 DOI: 10.1016/S0040-4039(00)61086-9

Air & Water Reactions

Slightly water soluble .

Reactivity Profile

Piperonyl aldehyde is an aldehyde. Aldehydes are frequently involved in self-condensation or polymerization reactions. These reactions are exothermic; they are often catalyzed by acid. Aldehydes are readily oxidized to give carboxylic acids. Flammable and/or toxic gases are generated by the combination of aldehydes with azo, diazo compounds, dithiocarbamates, nitrides, and strong reducing agents. Aldehydes can react with air to give first peroxo acids, and ultimately carboxylic acids. These autoxidation reactions are activated by light, catalyzed by salts of transition metals, and are autocatalytic (catalyzed by the products of the reaction). The addition of stabilizers (antioxidants) to shipments of aldehydes retards autoxidation. Piperonyl aldehyde is sensitive to light. Piperonyl aldehyde may react with oxidizing materials.

Fire Hazard

Flash point data for Piperonyl aldehyde are not available. Piperonyl aldehyde is probably combustible.

Flammability and Explosibility

Notclassified

Safety Profile

Moderately toxic by ingestion and intraperitoneal routes. Can cause central nervous system depression. A human skin irritant. Mutation data reported. Combustible when exposed to heat or flame; can react with oxidizing materials. See also ALDEHYDES.

Metabolism

In the animal body heliotropin undergoes the expected metabolic reaction involving oxidation to the corresponding acid (Williams, 1959).

Purification Methods

Crystallise piperonal from aqueous 70% EtOH or EtOH/water. [Beilstein 19/4 V 225.]

Upstream product

• 274-09-9 Methylenedioxybenzene 
• 20850-43-5 5-(chloromethyl)-1,3-benzodioxole 
• 94-59-7 1-allyl-3,4-methylenedioxybenzene 
• 25054-53-9 3,4-(methylenedioxy)benzoyl chloride 
• 64-18-6 formic acid 
• 10584-67-5 1-dichloromethyl-3,4-methylenedioxybenzene 
• 2861-28-1 1,3-benzodioxole-5-acetic acid 
• 62396-98-9 benzo[1,3]dioxol-5-yl-oxo-acetic acid 
• 406190-94-1 piperonylic acid-(N'-benzenesulfonyl-hydrazide) 
• 623-11-0 1-methyl-4-nitrosobenzene 
• 98-09-9 benzenesulfonyl chloride 
• 95794-11-9 N-(benzo[d][1,3]dioxol-5-ylmethylene)aniline oxide 
• 586-96-9 Nitrosobenzene 
• 71-43-2 benzene 

Downstream Products

• 3162-29-6 1-(benzo[d][1,3]dioxol-6-yl)ethanone 
• 7470-44-2 safrole 2',3'-oxide 
• 51003-16-8 trans-1-(3,4-methylenedioxyphenyl)-2-phenylethylene 
• 42307-51-7 (Z)-3-(3,4-methylenedioxyphenyl)-2-phenylprop-2-enoic acid 
• 42518-30-9 5-(Z)-benzo[1,3]dioxol-5-ylmethylene-3-phenyl-thiazolidine-2,4-dione 
• 158117-67-0 2,4-dinitro-3',4'-methylenedioxystilbene 
• 28281-49-4 3,4-methylenedioxypropiophenone 
• 1002342-12-2 3c-benzo[1,3]dioxol-5-yl-2-[2]thienyl-acrylonitrile 
• 35546-62-4 benzo[1,3]dioxol-5-ylmethylene-[1,2,4]triazol-4-yl-amine 
• 77669-23-9 (E)-2-(2-(benzo[d][1,3]dioxol-5-yl)vinyl)quinoline 
• 28824-65-9 5-Piperonyliden-2-thiohydantoin 
• 6318-41-8 AS041164 
• 28824-66-0 (5Z)-5-(1,3-benzodioxol-5-ylmethylene)-2-thioxo-1,3-thiazolidin-4-one 
• 28824-66-0 5-(1,3-benzodioxol-5-ylmethylidene)-2-thioxo-1,3-thiazolidin-4-one 

Relevant articles and documents

Production of piperonal, vanillin, and p-anisaldehyde via solventless supported iodobenzene diacetate oxidation of isosafrol, isoeugenol, and anethol under microwave irradiation

A novel experimental procedure to obtain carbonyl compounds under microwave irradiation from activated olefins and supported iodobenzene diacetate is described. By varying the reaction conditions it is possible to generate the corresponding aldehydes in reasonable-to-excellent yields and selectivities. The methodology is simple, clean, and reproducible and presents short reaction times. Using isosafrol, isoeugenol, and anethol it was possible to produce piperonal, vanillin and p-anisaldehyde, respectively.

Productive utilization of chlorobenzene: Palladium-catalyzed selective oxidation of alcohols

(Matrix presented) The palladium/ligand-catalyzed activation of chlorobenzene provides a general, efficient, and functional group friendly method for the selective oxidation of alcohols to carbonyl compounds.

One-Pot Catalytic Approach for the Selective Aerobic Synthesis of Imines from Alcohols and Amines Using Efficient Arene Diruthenium(II) Catalysts under Mild Conditions

A green and efficient catalytic approach for the selective synthesis of imines in air at room temperature was achieved with the aid of newly synthesised diruthenium(II) complexes [(η6-p-cymene)2Ru2Cl2(μ-L)] containing substituted 1,2-diacylhydrazine ligands. All the new complexes were fully characterised by analytical and spectroscopic techniques. The solid-state structure of a representative complex was solved by single-crystal X-ray diffraction analysis. The diruthenium(II) complexes also enable the selective aerobic oxidation of alcohols to aldehydes. The catalytic reaction operates in the presence of air as a green and cheap oxidant, and releases water as the only by-product. A plausible mechanism is proposed for the imine formation, which is believed to proceed via an aldehyde intermediate.

CHEMOSELECTIVE OXIDATION OF BENZYLIC ALCOHOLS BY FREMY'S SALT

A promising chemoselective oxidation of benzylic alcohols has been achieved by using Fremy's salt under phase-transfer conditions.Allylic and saturated alcohols were recovered unchanged.

Asymmetric glycolate alkylation approach towards total synthesis of 8-O.6′ and 8-O.4′-neolignans

The glycolate alkylation approach for the total synthesis of 8-O.6′ and 8-O.4′-neolignans has been optimized affording the natural products with high overall yields and excellent stereoselectivity. The developed approach can be further utilized towards the synthesis of many natural and unnatural neolignans. This is the first approach for the synthesis of neolignans using asymmetric glycolate alkylation approach.

A facile route to a polymer-supported IBX reagent

A three-step preparation of a polymer-supported IBX reagent from poly(p-methylstyrene) is reported. This reagent has been used successfully for the efficient oxidation of a series of alcohols to the corresponding aldehydes.

A new synthesis of aldehydes by the palladium-catalyzed reaction of 2-pyridinyl esters with hydrosilanes

A new synthesis of aldehydes by the palladium-catalyzed reaction of 2-pyridinyl esters with hydrosilanes is described. The reaction is applicable to the preparation of aliphatic, aromatic, and α,β-unsaturated aldehydes. Various functional groups, such as fluoro, methoxy, aldehyde, acetal, and ester, are tolerated. Georg Thieme Verlag Stuttgart.

Optimization of substituted cinnamic acyl sulfonamide derivatives as tubulin polymerization inhibitors with anticancer activity

A new series of novel cinnamic acyl sulfonamide derivatives were designed and synthesized and evaluated their anti-tubulin polymerization activities and anticancer activities. One of these compounds, compound 5a with a benzdioxan group, was observed to be an excellent tubulin inhibitor (IC50 = 0.88 μM) and display the best antiproliferative activity against MCF-7 with an IC50 value of 0.17 μg/mL. Docking simulation was performed to insert compound 5a into the crystal structure of tubulin at colchicine binding site to determine the probable binding model. 3D-QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent anti-tubulin polymerization activity.

A simple biomimetic protocol for the oxidation of alcohols with sodium hypochlorite in the presence of β-cyclodextrin in water

A simple and efficient protocol, which is inexpensive, convenient, clean, and facile, for oxidation of alcohols to carbonyl compounds has been developed using sodium hypochlorite in the presence of β-cyclodextrin with water as solvent. A series of alcohols were oxidized at room temperature in excellent yields.

Design, synthesis, and anti-inflammatory activity of caffeoyl salicylate analogs as NO production inhibitors

Chlorogenic acid (CGA) has been reported to exhibit potent anti-inflammatory activity. However, the development of anti-inflammatory agent based on CGA has not been investigated. In this paper, a series of caffeoyl salicylate compounds derived from CGA were designed, synthesized, and evaluated by LPS-induced nitric oxide synthase inhibition and QRT-PCR technique. Most compounds showed modest activity to inhibit production of nitric oxide (NO) in RAW 264.7 cells induced by lipopolysaccharides (LPS). Among these compounds, QRT-PCR and western blotting results indicated that compounds 6b, 6c, 6f, 6g and D104 that possess 5-member ring or 6-member ring caused a significant inhibition against expression of the iNOS2 in LPS-induced macrophages. In addition, cytotoxic assay displayed most derivatives have good safety in vitro. This new promising scaffold could be further exploited for the development of anti-inflammatory agent in the future.