112111-43-0

Usage

Chemical Properties

White Solid

Originator

Cephalon (US)

Uses

Different sources of media describe the Uses of 112111-43-0 differently. You can refer to the following data:
1. Used for treatment of excessive sleepiness, a1-adrenoceptor agonist
2. Used for treatment of excessive sleepiness, α1-adrenoceptor agonist.
3. analeptic

Definition

ChEBI: A 2-[(diphenylmethyl)sulfinyl]acetamide that has R configuration at the sulfur atom. Like its racemate, modafinil, it is used for the treatment of sleeping disorders such as narcolepsy, obstructive sleep apnoea, and shift-work sleep disord r. Peak concentration in the blood later occurs later following administration than with modafinil, so it is thought that armodafinil may be more effective than modafinil in treating people with excessive daytime sleepiness.

Brand name

Nuvigil

Synthesis

Armodafinil can be obtained starting from (+)-2( diphenylmethylsulfinyl)acetic acid via optical resolution using S-(-)-amethylbenzylamine, followed by esterification to the methyl ester and subsequent amidation with ammonium hydroxide. It can also be derived enantioselectively from 2-(diphenylmethylthio)acetamide via asymmetric oxidation with cumene hydroperoxide and titanium isopropoxide-S,Sdiethyl tartrate complex.

InChI:InChI=1/C15H15NO2S/c16-14(17)11-19(18)15(12-7-3-1-4-8-12)13-9-5-2-6-10-13/h1-10,15H,11H2,(H2,16,17)

Upstream product

• 68524-30-1 2-(diphenylmethylthio)acetamide 
• 90-99-3 diphenylchloromethane 
• 101-81-5 Diphenylmethane 
• 112111-45-2 (R)-Modafinil acid 
• 91-01-0 1,1-Diphenylmethanol 
• 63547-22-8 (benzhydrylthio)acetic acid 
• 713134-72-6 (R)-(-)-methyl (diphenylmethanesulfinyl)-acetate 
• 79-07-2 Chloroacetamide 
• 63547-25-1 methyl (S)-2-(benzhydrylsulfinyl)acetate 
• 68524-29-8 benzhydrylsulfanyl acetyl chloride 
• 63547-24-0 modafinil acid 
• 118286-24-1 methyl diphenylmethylmercaptoacetate 
• 776-74-9 Bromodiphenylmethane 
• 118286-19-4 (diphenylmethyl)(ethyl acetate)sulfoxide 

Downstream Products

• 1502873-99-5 C₂₀H₁₉NO₅S 
• 947318-12-9 2-[(R)-(diphenylmethyl)sulfinyl]acetamide monohydrate 
• 1502874-00-1 C₁₉H₁₇NO₅S 

Relevant academic research and scientific papers

Vanadium–Schiff base complex-functionalized SBA-15 as a heterogeneous catalyst: synthesis, characterization and application in pharmaceutical sulfoxidation of sulfids

VO2(picolinichydrazone) complex as a catalyst was stabilized on a SBA-15 mesoporous silica as a catalytic support by using (3-chloropropyl)triethoxysilane as a connector. SBA-15 is nanoporous and has a high ratio of surface area to volume. The immobilization of a metal–Schiff base complex to the surface area of SBA-15 can improve its catalytic effects by increasing the catalytic surface area. Unlike homogeneous catalysts, heterogeneous catalysts can be recovered and reused several times without any significant loss of catalytic activity. A vanadium–Schiff base complex-functionalized SBA-15 was synthesized by covalency connected by a pre-synthesised VO2(picolinichydrazone) complex to silanated SBA-15. The synthesized vanadium–Schiff base complex was characterized by proton nuclear magnetic resonance (1H NMR) spectroscopy, carbon nuclear magnetic resonance (13C NMR) spectroscopy and Fourier transform infrared spectroscopy (FT-IR), and the final V/SBA-15 was characterized by FT-IR, ultraviolet–visible spectrophotometry and X-ray powder diffraction. The morphology of V/SBA-15 was also obtained by scanning electron microscopy and transmission electron microscopy. The catalytic effect was examined by using V/SBA-15 as a heterogeneous catalyst in sulfoxidation reactions. The synthesis of modafinil and modafinic acid by pharmaceutical sulfoxidation of solfides was carried out and the effects of different solvents, reaction times and also recoverability and reusability of the heterogeneous catalyst were investigated. This catalyst showed high yield of sulfide conversion, stability and recyclability in the sulfoxidation of sulfides.

Two-Phase Oxidations with Aqueous Hydrogen Peroxide Catalyzed by Amphiphilic Pyridinium and Diazinium Salts

Amphiphilic pyridinium and diazinium salts were shown to be effective catalysts in two-phase (water/chloroform or water/dichloromethane) sulfoxidations and N-oxidations with hydrogen peroxide under mild conditions. This unprecedented oxidation method utilizes covalent bonding of hydrogen peroxide to a simple pyridinium or diazinium nucleus to increase the lipophilicity of the hydroperoxide species and to subsequently activate it for oxidations in a non-polar medium. The catalytic efficiency was found to depend on the type of heteroarenium core and on the lipophilicity of the catalyst. Five series of heteroarenium catalysts were prepared and investigated: 1-Alkyl-3,5-dicyanopyridinium, 1-alkyl-3,5-dinitropyridinium, 1-alkyl-3-cyanopyrazinium, 1-alkyl-4-cyanopyrimidinium and 1-alkyl-4-(trifluoromethyl)pyrimidinium triflates (alkyl=butyl, hexyl, octyl, decyl, dodecyl and hexadecyl). Among them, the 1-octyl-3,5-dinitropyridinium and 1-decyl-4-(trifluoromethyl)pyrimidinium triflates were found to be superior catalysts, showing the best stability and the highest catalytic activity, achieving acceleration by a factor of 350 relative to the non-catalyzed reaction. In contrast to other organocatalytic two-phase oxidations that use hydrogen peroxide, the presented method is characterized by high chemoselectivity and low catalyst loading (5mol%) and with the reactions being performed under mild conditions, that is, at 25 C using diluted hydrogen peroxide and a non-basic aqueous phase. The catalysts have simple structures and are readily available from commercial materials. Practical applications are demonstrated via the oxidation of several types of sulfides and amines.

New synthetic route to modafinil drug including desulfobenzhydrylation of sodium carbamoylmethyl thiosulfate: Experimental and quantum chemical studies

A new synthetic route to 2-benzhydrylsulfinylacetamide (1), a nootropic drug modafinil, is described. The synthesis includes the alkylation of sodium thiosulfate with chloroacetamide to sodium carbamoylmethyl thiosulfate, the desulfobenzhydrylation of the latter by benzhydrol in formic acid to form benzhydrylthioacetamide (3a), and the further oxidation of this thioamide with hydrogen peroxide. According to B3LYP/6-31G** DFT calculations, the key step of the synthesis, namely, desulfobenzhydrylation of salt 6a, occurs only insignificantly due to the energetically unfavorable direct attack of this salt by benzhydryl formate; the reaction mainly involves the attack by the benzhydrilium carbocation Ph2CH+. The oxidation of sulfide 3a to sulfinylacetamide 1 is efficiently catalyzed by side proton-donor molecules (constituents of the transition states of the reaction). The oxidant can be the anionic form of the reactant (HO2- ion), which reacts with sulfide 3a via the unusual noncatalytic mechanism. At the step of transition state formation, this mechanism resembles the S N2 substitution.

Luminescent cis-Bis(bipyridyl)ruthenium(II) Complexes with 1,2-Azolylamidino Ligands: Photophysical, Electrochemical Studies, and Photocatalytic Oxidation of Thioethers

New 1,2-azolylamidino complexes cis-[Ru(bipy)2(NH=C(R)az*-κ2N,N)](OTf)2 (R = Me, Ph; az? = pz, indz, dmpz) are synthesized via chloride abstraction after a subsequent base-catalyzed coupling of a nitrile with the previously coordinated 1,2-azole. The synt

Self-repairing metal-organic hybrid complexes for reinforcing immobilized chloroperoxidase reusability

A self-repairing metal-enzyme hybrid nanocatalyst with a sodium alginate (SA) coating was reported in this study. Compared with free CPO, immobilized chloroperoxidase (CPO) has similar Km and Kcat values. SA-coated CPO@Ca3

Efficient atom and step economic (EASE) synthesis of the "smart drug" Modafinil

Modafinil (2-[(diphenylmethyl)sulfinyl]acetamide, MOD) is a key psychostimulant drug used for the treatment of narcolepsy and other sleep disorders that has a very low addiction liability. Recently, MOD has been clinically investigated for the treatment of cocaine addiction and used by astronauts in long-term space missions. We have developed a synthetic strategy for "smart drug" Modafinil. An efficient atom and step economic (EASE) synthesis has been carried out by the direct reaction of benzhydrol and 2-mercaptoacetamide using the recyclable heterogeneous catalyst Nafion-H along with post-sulfoxidation. This protocol exhibits improved sustainability credentials. We have also developed a superior pre-sulfoxidation approach for the synthesis of Modafinil.

Microbial oxidation/amidation of benzhydrylsulfanyl acetic acid. Synthesis of (+)-modafinil

A highly enantioselective oxidation of benzhydrylsulfanyl acetic acid to the corresponding (S)-sulfinyl carboxylic acid was achieved employing the fungus Beauveria bassiana in very good yield. This product was amidated using the bacteria Bacillus subtilis to afford (S)-modafinil in good yield.

Asymmetric synthesis of modafinil and its derivatives by enantioselective oxidation of thioethers: comparison of various methods including synthesis in ionic liquids

The oxidation of 2-(benzhydrylthio)acetic acid and its derivatives was performed with various catalytic and stoichiometric enantioselective reagents, the best results being obtained with stoichiometric chiral oxaziridine 5. The use of [bmim][PF6] as a solvent with 5 gave slightly higher yields and, in the case of the model compound thioanisole, a reversal of the enantioselectivity.

One-pot parallel synthesis of alkyl sulfides, sulfoxides, and sulfones

A simple and cost-effective one-pot parallel synthesis approach to sulfides, sulfoxides, and sulfones from thiourea was elaborated. The method combines two procedures optimized to the parallel synthesis conditions: alkylation of thiourea with alkyl chlorides and mono or full oxidation of in situ generated sulfides with H2O2 or H2O2-(NH4)2MoO4. The experimental set up required commonly used lab equipment: conventional oven and ultrasonic bath; the work up includes filtration or extraction with chloroform. The method was evaluated on an 81 member library of drug-like sulfides, sulfoxides, and sulfones yielding the compounds on a 30-300 mg scale. A small-scale synthesis of 2-(benzhydrylsulfinyl)acetamide (modafinil) utilizing our approach resulted in similar efficiency to the published procedures.

Spectroscopic and molecular modeling methods to investigate the interaction between psycho-stimulant modafinil and calf thymus DNA using ethidium bromide as a fluorescence probe

Interaction type of modafinil with calf thymus DNA (ct-DNA) was examined systematically using ethidium bromide (EB) as a fluorescence probe by fluorescence spectroscopy, UV–Vis spectroscopy, viscosity and molecular docking method. The fluorescence quenchi