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
• Article Data: 343

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

Synthesis

Different sources of media describe the Synthesis of 120-57-0 differently. You can refer to the following data:
1. 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.
2. By the oxidation of isosafrole with potassium dichromate and sulfuric acid and subsequent steam distillation of piperonal

Chemical Properties

Different sources of media describe the Chemical Properties of 120-57-0 differently. You can refer to the following data:
1. white crystalline solid
2. Piperonal has a sweet, flowery odor reminiscent of heliotrope and a bittersweet taste.
3. Heliotropin occurs in a number of essential oils, but only in low concentrations. It forms white crystals (mp 37°C) with a sweet, floral, slightly spicy, heliotrope-like odor.

Occurrence

Reported found in the essential oils of Robinia pseudo-acacia and Eryngium poterium; in the oils of Spirea ulmaria and of leaves of Doryphora sassafras; also reported found in Tahitian and Bourbon vanilla, camphor wood oil, violet flowers concrete and absolute, burley tobacco, rabbiteye blueberry, melon, pepper, cooked chicken, sherry and dill.

Uses

Different sources of media describe the Uses of 120-57-0 differently. You can refer to the following data:
1. Piperonal is an impurity of Tadalafil (T004500). Tadalafil impurity A.
2. In perfumery, in cherry and vanilla flavors, in organic syntheses.
3. Piperonal is used as fragrance and flavoring agent.

Definition

ChEBI: An arenecarbaldehyde that is 1,3-benzodioxole substituted by a formyl substituent at position 5. It has been isolated from Piper nigrum.

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 .

Aroma threshold values

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.

Taste threshold values

Taste characteristics at 10 to 50 ppm: ripe black cherry fleshy, ripe berry, sweet, macaroon, Jordan almond, creamy vanilla, spicy cream soda, courmarin, slight floral with hay nuances.

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

General Description

Colorless lustrous crystals.

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 
• 27738-46-1 3,4-(methylenedioxy)mandelic acid 
• 406190-94-1 piperonylic acid-(N'-benzenesulfonyl-hydrazide) 
• 623-11-0 1-methyl-4-nitrosobenzene 
• 98-09-9 benzenesulfonyl chloride 
• 64-17-5 ethanol 
• 64-19-7 acetic acid 

Downstream Products

• 3162-29-6 1-(benzo[d][1,3]dioxol-6-yl)ethanone 
• 7470-44-2 safrole 2',3'-oxide 
• 28824-65-9 5-Piperonyliden-2-thiohydantoin 
• 60546-62-5 6-bromopiperonylic acid 
• 15930-53-7 6-bromo-3,4-methylenedioxybenzaldehyde 
• 139-85-5 3,4-dihydroxybenzaldehyde 
• 1400815-07-7 (E)-N'-(benzo[d][1,3]dioxol-5-ylmethylene)thiophene-2-carbohydrazide 
• 17253-14-4 2-benzo[1,3]dioxol-5-yl-indan-1,3-dione 
• 109695-11-6 (E)-2-(2-(benzo[d][1,3]dioxol-5-yl)vinyl)-4H-chromen-4-one 
• 735-97-7 Heliotropin-isonicotinoylhydrazon 
• 4551-03-5 5-<(3,4-methylenedioxyphenyl) methylene>-2,4,6 (1H,3H,5H)pyrimidinetrione 
• 74051-76-6 5-(benzo[d][1,3]dioxol-5-ylmethylene)-2-thioxodihydropyrimidine-4,6(1H,5H)-dione 
• 80554-37-6 3-[(E)-piperonylidene-chroman-4-one 
• 6286-57-3 4-benzo[1,3]dioxol-5-ylmethylene-3-phenyl-4H-isoxazol-5-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.

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.

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 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.

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.

Amino Benzamidoxime (ABAO)-Based Assay to Identify Efficient Aldehyde-Producing Pichia pastoris Clones

The chemoselective synthesis of aldehydes is a challenging task. Nature provides carboxylic acid reductases (CARs) as elegant tools for the direct reduction of carboxylic acids to their respective aldehydes. The discovery of new CARs and strains that efficiently produce these enzymes necessitates a robust high-throughput assay with selectivity for aldehydes. We recently reported a simple assay that allows the substrate independent and chemoselective quantification of aldehydes (irrespective of their chemical structure). The assay utilized amino benzamidoxime (ABAO), which forms UV-active and fluorescent dihydroquinazolines. In this study, we adapted the ABAO-assay for the identification and comparison of Pichia pastoris clones with the ability to produce aldehydes from carboxylic acids. Specifically, CAR and PPTase from Mycobacterium marinum (MmCAR and MmPPTase) were co-expressed using different bidirectional promoters (BDPs). A library of 598 clones was screened for piperonal production with the ABAO assay and the results were validated by HPLC quantification. 1 OD unit of the best Pichia pastoris clone 2.A7, regulating MmCAR and MmPPTase expression by two strong constitutive promoters, fully converted 5 mM of piperonylic acid within 2 h. (Figure presented.).

Structural optimization of caffeoyl salicylate scaffold as NO production inhibitors

Chlorogenic acid (CGA) has been considered as one of important active components in a number of medicinal herbs. Recently our group demonstrated that caffeoyl salicylate scaffold derived from CGA can be employed for the development of novel anti-inflammatory agents. The most active compound D104 can be a very promising starting point for the further structural optimization. A series of novel caffeoyl salicylate analogs were designed, synthesized, and evaluated by preliminary biological evaluation. The obtained results showed that the two compounds B12 and B13 can not only inhibit production of nitric oxide (NO) in RAW264.7 cells induced by lipopolysaccharides (LPS) effectively, but also have high safety in in vitro cytotoxic test, which could be comparable with D104. Molecular docking study on the peroxisome proliferator-activated receptor γ (PPARγ) protein revealed that compounds B12 and B13 can follow the same binding mode with D104, and the carboxyl group of caffeoyl salicylate scaffold might play a key role in the interaction with protein target, which implied the carboxyl group should be retained in the further optimization.

Design, synthesis, biological evaluation, homology modeling and docking studies of (E)-3-(benzo[d][1,3]dioxol-5-ylmethylene) pyrrolidin-2-one derivatives as potent anticonvulsant agents

A series of (E)-3-(benzo[d][1,3]dioxol-5-ylmethylene)pyrrolidin-2-one derivatives were designed, synthesized, and evaluated for their anticonvulsant activities. In the preliminary screening, compounds 5, 6a–6f and 6h–6i showed promising anticonvulsant activities in MES model, while 6f and 6g represented protection against seizures at doses of 100 mg/kg and 0.5 h in scPTZ model. The most active compound 6d had a high-degree protection against the MES-induced seizures with ED50 value of 4.3 mg/kg and TD50 value of 160.9 mg/kg after intraperitoneal (i.p.) injection in mice, which provided 6d in a high protective index (TD50/ED50) of 37.4 comparable to the reference drugs. Beyond that, 6d has been selected and evaluated in vitro experiment to estimate the activation impact. Apparently, 6d clearly inhibits the Nav1.1 channel. Our preliminary results provide new insights for the development of small-molecule activators targeting specifically Nav1.1 channels to design potential drugs for treating epilepsy. The computational parameters, such as homology modeling, docking study, and ADME prediction, were made to exploit the results.

Simple system for oxidation of alcohols in aqueous solution

A simple and mild system for conversion of primary and secondary alcohols to corresponding aldehydes and ketones has been developed using aqueous sodium dichloroiodate at room temperature in water. This novel application of aqueous sodium dichloroiodate gives high yield and offers a number of advantages in terms of safety and ease of use in comparison to other methods that often employ toxic and hazardous solvents and materials. Copyright Taylor & Francis Group, LLC.

Design and Synthesis of 5-Substituted Benzo[d][1,3]dioxole Derivatives as Potent Anticonvulsant Agents

A series of 5-substituted benzo[d][1,3]dioxole derivatives was designed, synthesized, and tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens. Neurotoxicity was determined by rotarod test. In the preliminary screening, six compounds, 3a, 3c, 3d, and 4d–f, showed promising anticonvulsant activities in the MES model, and compounds 4c and 4d exhibited full protection against seizures at doses of 300 mg/kg in the scPTZ model. Among the synthesized compounds, 3c as the most active compound showed high protection against the MES-induced seizures with an ED50 value of 9.8 mg/kg and a TD50 value of 229.4 mg/kg after intraperitoneal injection into mice, thus providing compound 3c with a high protective index (TD50/ED50) of 23.4 comparable to those of reference antiepileptic drugs.

Heterogeneous Oxidation of Allylic and Benzylic Alcohols Catalyzed by Ru-Al-Mg Hydrotalcites in the Presence of Molecular Oxygen

-

Efficient and green oxidation of alcohols with tert-butyl hydrogenperoxide catalyzed by a recyclable magnetic core-shell nanoparticle-supported oxo-vanadium ephedrine complex

A novel method for the oxidation of alcohols to the corresponding carbonyl compounds has been successfully developed using tert-butyl hydrogenperoxide (TBHP) in the presence of a catalytic amount of recyclable magnetic nanoparticle-supported oxo-vanadium ephedrine complex (VO(ephedrine)2@MNPs) in PEG as a green solvent at 80?°C. The catalyst can be magnetically recycled and successfully reused in six subsequent reaction cycles with only slight decreases of its catalytic activity.

Aerobic oxidation of alcohols enabled by nitrogen-doped copper nanoparticle catalysts

Heterogeneous nitrogen-doped carbon-incarcerated copper nanoparticle catalysts have been developed. The catalysts promoted the oxidation of alcohols to the corresponding aldehydes, including aliphatic substrates, in high yield in the presence of an N-oxyl

Nickel(II)-Catalyzed Selective (E)-Olefination of Methyl Heteroarenes Using Benzyl Alcohols via Acceptorless Dehydrogenative Coupling Reaction

An efficient catalytic protocol for the synthesis of selective (E)-olefins by the newly synthesized nickel complexes via greener acceptorless dehydrogenative coupling methodology is presented. Two nickel(II) N, S chelating complexes were structurally characterized with the aid of spectral and single crystal X-ray diffraction methods. Olefination of 2-methylheteroarenes with benzyl alcohols via acceptorless dehydrogenative coupling is achieved by inexpensive nickel(II) catalysts. The present olefination protocol is simple and furnishes the desired 2-alkenylheteroarenes in 35 h and yields in the range of 40–93 %. The dehydrogenative coupling reaction proceeds via the generation of an aldehyde intermediate and produces water and hydrogen as sole by-products. The wide substrate scope of this catalytic reaction covered the synthesis of drug intermediates.

NOVEL HETEROCYCLIC DERIVATIVES WITH CARDIOMYOCYTE PROLIFERATION ACTIVITY FOR TREATMENT OF HEART DISEASES

Provided are novel heterocyclic derivatives with cardiomyocyte proliferation activity for treatment of heart diseases. Specifically, provided are the compounds of formula (I) or pharmaceutically acceptable salts, stereoisomers, solvates or prodrugs, prepa