94-58-6

Usage

Uses

DIHYDROSAFROL is used as a chemical intermediate in the synthesis of various compounds, including pharmaceuticals and fragrances, due to its unique chemical properties. However, its use is limited due to its carcinogenic nature, and it is essential to handle it with caution and follow safety guidelines to minimize exposure and potential health risks.

Preparation

By catalytic hydrogenation of safrole (Arctander, 1969).

Toxicity evaluation

The acute oral LD50 was reported as 2.26 g/kg (1.84-2.78 g/kg) in rats and as 4.30 g/kg in the mouse (Jenner, Hagan, Taylor, Cook & Fitzhugh, 1964). The acute dermal LD50 in rabbits was reported as > 5 g/kg (Shelanski & Moldovan, 1973). Daily dosage for 4 days with 770 mg dihydrosafrole/kg caused macroscopic liver lesions and one death in six treated rats (Taylor, Jenner & Jones, 1964).

Safety Profile

Confirmed carcinogen with experimental carcinogenic data. Moderately toxic by ingestion and intraperitoneal routes. A skin irritant. When heated to decomposition it emits acrid smoke and irritating fumes.

InChI:InChI=1/C10H12O2/c1-2-3-8-4-5-9-10(6-8)12-7-11-9/h4-6H,2-3,7H2,1H3

Upstream product

• 94-59-7 1-allyl-3,4-methylenedioxybenzene 
• 58095-77-5 (E)-3,4-methylenedioxycinnamaldehyde 
• 4676-39-5 1-(1,3-benzodioxol-5-yl)-2-propanone 
• 120-58-1 isosafrole 
• 6890-30-8 1-piperonyl-1-propanol 
• 64-17-5 ethanol 
• 4043-71-4 isosafrole 
• 120-57-0 piperonal 
• 28281-49-4 3,4-methylenedioxypropiophenone 
• 2525-02-2 4-propylbenzene-1,2-diol 
• 18815-73-1 methylzinc iodide 
• 274-09-9 Methylenedioxybenzene 
• 6006-82-2 3,4-methylenedioxyphenethyl alcohol 
• 124-63-0 methanesulfonyl chloride 

Downstream Products

• 1938-32-5 5-(chloromethyl)-6-propyl-1,3-benzodioxole 
• 34827-26-4 bis(2-propyl-4,5-methylenedioxyphenyl)methane 
• 114888-84-5 5-[4-(3-chloro-propyl)-benzyl]-6-propyl-benzo[1,3]dioxole 
• 68399-69-9 2-ethoxy-5-propyl-phenol 
• 2785-87-7 2-methoxy-4-n-propylphenol 
• 58539-27-8 2-methoxy-4-propylphenol 
• 23950-94-9 methyl-(3-propyl-cyclohexyl)-ether 
• 2525-02-2 4-propylbenzene-1,2-diol 
• 77866-58-1 trans-4-propylcyclohexanol 
• 33943-26-9 dihydroeugenol acetate 
• 89266-70-6 4-propyl-1,2-phenyl diacetate 
• 58095-77-5 (E)-3,4-methylenedioxycinnamaldehyde 
• 4043-71-4 isosafrole 
• 28281-49-4 3,4-methylenedioxypropiophenone 

Relevant academic research and scientific papers

Sonoelectrochemical hydrogenation of safrole: A reactor design, statistical analysis and computational fluid dynamic approach

In this work, ultrasound-assisted electrocatalytic hydrogenation (US-ECHSA) of safrole was carried out in water medium, using sacrificial anode of nickel. The ultrasonic irradiation was carried out at frequency of 20 kHz ± 500 Hz with a titanium cylindrical horn (MS 73 microtip; Ti-6AI-4V alloy; 3.0 mm diameter). The optimal conditions were analyzed by statistical experimental design (fractional factorial). The influence of the sonoelectrochemical reactor design was also investigated by using computational fluid dynamics as simulation tool. Among the five parameters studied: catalyst type, use of β-cyclodextrin as inverse phase transfer catalyst, sonoelectrochemical reactor design, ultrasound mode and the temperature of the solution, only the last three were significant. The hydrogenation product, dihydrosafrole, reached 94% yield, depending on the experimental conditions applied. Data of computational fluid dynamics showed that a wing shape tube added to the sonoelectrochemical reactor can work as a cooling apparatus, during the electrochemical process. The reactional solution temperature diminishes 14 °C when compared to the four-way-type reactor. Cooper cathode, absence of β-cyclodextrin, four-way-type reactor, ultrasound continuous mode (14 W) and absence of temperature control were the most effective reaction parameters for the safrole hydrogenation using US-ECHSA method. The proposed approach represents an important contribution for understanding the hydrodynamic behavior of sonoelectrochemical reactors designs and, consequently, for the reducing of the experimental costs inherent to the sonoelectrochemical process.

AN EFFICIENT PROCESS FOR PREPARATION OF ACYL DERIVATIVES OF ALKYLENEDIOXYBENZENES

The present disclosure provides a process of preparation of compounds of Formula I comprising the step of : reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent, wherein the step of reacting the alkylenedioxybenzene compound of Formula II with the acyl halide of Formula III is effected in presence of an amphoteric oxide and a Lewis acid so as to immediately quench the compound of formula H-X, formed during the course of the reaction, to substantially eliminate degradation of the compound of any of Formula I and II. The present disclosure also provides for process(es) for preparation of compound of Formula IVa, IVb and IVc.

Harnessing Alkylpyridinium Salts as Electrophiles in Deaminative Alkyl-Alkyl Cross-Couplings

A Negishi cross-coupling of alkylpyridinium salts and alkylzinc halides has been developed. This is the first example of alkyl-alkyl bond formation via cross-coupling of an alkyl amine derivative with an unactivated alkyl group, and allows both primary and secondary alkylpyridinium salts to react with primary alkylzinc halides with high functional group tolerance. When combined with formation of the pyridinium salts from primary amines, this method enables the noncanonical transformation of NH2 groups into a wide range of alkyl substituents with broad functional group tolerance.

A PROCESS FOR PREPARATION OF ALKENYL AND ALKYL DERIVATIVES OF ALKYLENEDIOXYBENZENE

The present disclosure generally relates to the method of preparation of compounds of Formula IV. An aspect of the present disclosure relates to a process for preparation of compound of Formula IV, said process comprising the step of reacting an alkylenedioxybenzene compound of Formula II with an acyl halide of Formula III in presence of a solvent, characterized in that the step of reacting the alkylenedioxybenzene compound of Formula II with the acyl halide of Formula III is effected in the presence of an amphoteric oxide so as to in-situ quench the compound of formula H-X formed during the course of the reaction, thereby substantially eliminating degradation of the compounds of Formula IV and Formula II.

A Co2B Mediated NaBH4 Reduction Protocol Applicable to a Selection of Functional Groups in Organic Synthesis

A high-yielding and high-rate reduction method that operates with alkenes, alkynes, azides, nitriles, and nitroarenes was developed and optimized. The method makes use of sodium borohydride reduction of CoSO4 under release of hydrogen along with the formation of Co2B as a nanoparticle material. The produced Co2B activates the various functional groups for hydride reduction. The protocol was proven to operate with an assortment of functional groups to provide good to excellent yields. Furthermore, the reduction method was successfully adapted, implemented, and developed for a continuous flow approach using the multi-jet oscillating disk (MJOD) flow reactor platform at atmospheric pressure.

Ruthenium nanoparticle-intercalated montmorillonite clay for solvent-free alkene hydrogenation reaction

Well-characterized, ruthenium nanoparticle-intercalated montmorillonite clay was used as a catalyst in solvent-free alkene hydrogenation reactions and the corresponding products were obtained in good yields. The catalytic activity of ruthenium nanoparticle-intercalated montmorillonite clay was successfully tested with 16 different functionalized and non-functionalized alkenes. Apart from alkene reduction, the ruthenium nanoparticle-intercalated montmorillonite clay was also tested in Wittig-type reactions for obtaining dehydrobrittonin A, an important intermediate for the synthesis of brittonin A. Ruthenium nanoparticle-intercalated montmorillonite clay was found to be active in the synthesis of dehydrobrittonin A and brittonin A. The ability to recycle the catalyst nine times, together with low catalyst loading, high catalytic activity and catalytic selectivity were noteworthy advantages of the proposed protocol.

Two-chamber hydrogen generation and application: Access to pressurized deuterium gas

Hydrogen and deuterium gas were produced and directly applied in a two-chamber system. These gaseous reagents were generated by the simple reaction of metallic zinc with HCl in water for H2 and DCl in deuterated water for D2. The setup proved efficient in classical Pd-catalyzed reductions of ketones, alkynes, alkenes, etc. in near-quantitative yields. The method was extended to the synthesis and isotope labeling of quinoline and 1,2,3,4-tetrahydroquinoline derivatives. Finally, CX-546 and Olaparib underwent efficient Ir-catalyzed hydrogen isotope exchange reactions.

β-cyclodextrin as inverse phase transfer catalyst on the electrocatalytic hydrogenation of organic compounds in water

The optimum conditions for the electrocatalytic hydrogenation (ECH) of benzaldehyde in water, using a nickel sacrificial anode (SA) (referred to as ECH-SA) and β-cyclodextrin (β-CyD) as inverse phase transfer catalyst (IPTC) were determined. Four parameters were investigated: the morphology of the nickel deposited on the cathode matrix (Cu, Fe, Ni or Fe/Ni alloy (64:36)) during a pre-electrolysis, the size of the CyD cavity, the concentration of β-CyD, the supporting electrolyte concentration and the current density applied. The results showed that a Ni matrix together with ultrasound pre-electrolysis treatment allowed a nanostructured nickel deposit on the cathode surface. Under the best electrolysis conditions (2.8 mmol dm -3 of β-CyD, 1.0 mol dm-3 of NH4Cl and a current density of 330 mA dm-2), the yield of benzyl alcohol (99%) was 27% higher than that obtained under the same conditions but in the absence of β-CyD. Taking into account the hydrophobic character of the β-CyD, the best conditions of the ECH-SA method were applied to the hydrogenation of a variety of organic substrates. Excellent yields and current efficiencies were obtained with arylbenzaldehydes and acetophenone. ECH-SA of styrene gave moderate yield and current efficiency, and the hydrogenation of a terminal non-conjugated olefin (safrole) was not efficient.

Ni(0)-CMC-Na nickel colloids in sodium carboxymethyl-cellulose: Catalytic evaluation in hydrogenation reactions

A recyclable catalyst, Ni(0)-CMC-Na, composed of nickel colloids dispersed in a water soluble bioorganic polymer, sodium carboxymethylcellulose (CMC-Na), was synthesized by a simple procedure from readily available reagents. The catalyst thus obtained is stable and highly active in alkene hydrogenations.

Larvicidal and structure-activity studies of natural phenylpropanoids and their semisynthetic derivatives against the tobacco armyworm Spodoptera litura (Fab.) (Lepidoptera: Noctuidae)

The larvicidal activity of 18 phenylpropanoids, 1-18, including phenylpropenoate, phenylpropenal, phenylpropene, and their semisynthetic analogues, were evaluated against the tobacco armyworm, Spodoptera litura (FAB.), to identify promising structures with insecticidal activity. Amongst various phenylpropanoids, isosafrole, a phenylpropene, showed the best activity, with an LC50 value of 0.6 μg/leaf cm2, followed by its hydrogenated derivative dihydrosafrole (LC50=2.7 μg/leaf cm 2). The overall larvicidal activity of various phenylpropene derivatives was observed in the following order: isosafrole (6) >dihydrosafrole (16)>safrole (12)>anethole (4)>methyl eugenol (11)>eugenol (13)>β-asarone (8)>dihydroasarone (18)>dihydroanethole (15). Dihydrosafrole might be a promising compound, although presenting a lower larvicidal activity than isosafrole, because of its better stability and resistance to oxidative degradation (due to the removal of the extremely reactive olefinic bond) in comparison to isosafrole. Such structure-activity relationship studies promote the identification of lead structures from natural sources for the development of larvicidal products against S. litura and related insect pests.