4657-12-9

Usage

Synthesis Reference(s)

The Journal of Organic Chemistry, 24, p. 1943, 1959 DOI: 10.1021/jo01094a029

InChI:InChI=1/C7H8O4S/c8-7(12(9,10)11)6-4-2-1-3-5-6/h1-5,7-8H,(H,9,10,11)

Upstream product

• 100-52-7 benzaldehyde 

Downstream Products

• 1574-10-3 benzaldehyde semicarbazone 
• 890-51-7 N-benzylidenenaphthalen-1-amine 
• 932-90-1 syn-benzaldehyde oxime 
• 5097-99-4 α-diethylaminophenylacetonitrile 
• 16663-94-8 phenylammonium 1-anilino-1-phenylmethanesulfonate 
• 46887-57-4 1-phenyl-1-phenylaminomethanesulfonic acid 
• 88485-95-4 [2]naphthylamino-phenyl-acetonitrile 
• 110989-32-7 N-(cyano(phenyl)methyl)-N-methylacetamide 
• 15190-66-6 2-(o-toluidino)-2-phenylacetonitrile 
• 797-20-6 N,N'-dibenzylidene-benzene-1,4-diamine 
• 3999-29-9 2-phenylimidazo[1,2-a]pyridin-3-amine 
• 66348-92-3 p-toluidinium p-toluidine-phenylmethanesulfonate 
• 532-28-5 (RS)-mandelonitrile 
• 100-52-7 benzaldehyde 

Relevant academic research and scientific papers

Bisulfite Addition Compounds as Substrates for Reductive Aminations in Water

Highly valued products resulting from reductive aminations utilizing shelf-stable bisulfite addition compounds of aldehydes can be made under aqueous micellar catalysis conditions. Readily available α-picolineborane serves as the stoichiometric hydride source. Recycling of the aqueous reaction medium is easily accomplished, and several applications to targets in the pharmaceutical industry are documented.

Synthesis, in vitro antiprotozoal activity, molecular docking and molecular dynamics studies of some new monocationic guanidinobenzimidazoles

A series of monocationic new guanidinobenzimidazole derivatives were prepared in a four step process starting from 2-nitro-1,4-phenylendiamine. Their antiparasitic activity against Plasmodium falciparum, Trypanosoma brucei rhodesiense, Trypanosoma cruzi and Leishmania donovani were evaluated in vitro. Two out of 20 tested monocationic compounds (7, 14) showed close activity with reference drug chloroquine against P. Falciparum. To understand the interactions between DNA minor groove and in vitro active compounds (7, 14) molecular docking studies were carried out. Stability and binding energies of DNA-ligand complexes formed by DNA with compounds 7 and 14 were measured by molecular dynamics simulations throughout 200 ns time. Root mean square deviation (RMSD) values of the ligands remained stable below 0.25 mm and root mean square fluctuation (RMSF) values of the active site residues with which it interacted decreased compared to the apo form. All compounds exhibited theoretical absorption, distribution, metabolism and excretion (ADME) profiles conforming to Lipinski's and Ghose's restrictive rules.

High-yield DL-mandelic acid synthesis process

The invention provides a high-yield DL-mandelic acid synthesis process. The synthesis process specifically comprises the following steps: 1, treating benzaldehyde by using sodium hydrogen sulfite to obtain benzaldehyde sodium hydrogen sulfite; 2, extracting the benzaldehyde sodium hydrogen sulfite by using an organic solvent, recovering unreacted benzaldehyde in the benzaldehyde sodium hydrogen sulfite, and adding sodium cyanide after the extraction is completed to prepare mandelonitrile; 3, adding an inorganic acid, and then carrying out heating and pressure maintaining treatment to hydrolyze the mandelonitrile so as to obtain mandelic acid; and 4, purifying the mandelic acid. According to the method, the step of extracting the p-benzaldehyde sodium hydrogen sulfite salt is added, so that the probability that the product purity is reduced due to benzoin condensation is reduced, the recycled benzaldehyde can be returned to the raw material for use, and the yield can be increased in multiple rounds of reactions; and the hydrolysis process of the mandelonitrile adopts heating and pressure maintaining treatment, so that consumption of inorganic acid can be reduced, and the hydrolysis efficiency is improved.

Benzimidazole derivatives as potent and isoform selective tumor-associated carbonic anhydrase IX/XII inhibitors

We describe the synthesis of a series of 2-arylbenzimidazole derivatives bearing sulfonamide functionality (4a–d, 7a–c and 10) as well as hydroxamic acid (15a–b), carboxylic acid (16a–b), carboxamide (17a–b) and boronic acid (22a–b and 26) functionalities, which act as human carbonic anhydrase (hCA, EC 4.2.1.1) inhibitors. The newly synthesized benzimidazole derivatives were evaluated against 4 physiologically relevant CA isoforms (hCA I, II, IX, and XII), and especially the sulfonamide-containing benzimidazoles demonstrated intriguing inhibitory activity against tumor associated CA IX and XII with KI values in the range of 5.2–29.3 nM and 9.9–41.7 nM, respectively. Notably, compound 4c was the most potent and selective CA IX (KI = 6.6 nM) and XII (KI = 9.9 nM) inhibitor with a significant selectivity ratio over cytosolic CA I and II isoforms in the range of 3.4–25.2. In addition, compounds having hydroxamic acid (15a-b) or carboxylic acid (16a-b) functionalities resulted in greater selectivity ratios for CA IX/XII over CAI/II in the range of 4.1–121.5 although with KI values in lower micromolar potency (KIs = 0.36–0.85 μM for CA IX/XII).

An efficient NaHSO3-promoted protocol for chemoselective synthesis of 2-substituted benzimidazoles in water

An efficient protocol for chemoselective synthesis of 2-substituted benzimidazoles from a variety of aliphatic/aromatic/ heteroaryl aldehydes and o-phenylenediamine derivatives promoted by NaHSO3 in water had been developed. The amount of NaHSO3 had a great effect on the reaction selectivity of 2-substituted benzimidazole and 1,2-disubstituted benzimidazole when the reaction was carried out in water. When the amount of the NaHSO3 was more than 11 equivalents, the 2-substituted benzimidazole could be highly selectively formed as the sole product. NaHSO3 was firstly reacted with aldehyde to form the aldehyde sodium bisulfite, which reacted with o-phenylenediamine to form the 2-substituted benzimidazole and inhibited the formation of 1,2-disubstituted benzimidazole. This protocol solved the poor selectivity problem appearing in traditional method when cyclocondensation between o-phenylenediamine and aldehydes. The method also had advantage of simple work up by filtrating the single 2-substituted benzimidazole precipitates from reaction mixture at the end of the reaction without further purification. In addition, the method was applicable to both electron-rich and electron-poor starting materials, which was successfully used for synthesizing nine novel 2-substituted benzimidazole derivatives containing a 1,2,3-triazole moiety. They were characterized by NMR, IR and HRMS spectrum. Moreover, this method had been applied to a large scale synthesis of 2-substituted benzimidazole derivatives.

Facile utilisation of aldehyde bisulfite adducts: Synthesis of (E)-1,2- diphenylethenes

Background: A one-pot coupling reaction of aldehyde bisulfite adducts was developed for McMurry reaction using Zn-TiCl4 in 1,4-dioxane solvent medium. The treatment of sodium hydroxy(phenyl)methane sulfonate (2a) with TiCl4 in 1,4-dioxane favoured the deprotection of the bisulfite adduct 2a, and the in situ regeneration of benzaldehyde (1a) underwent reductive coupling to afford stilbene 3a in a relatively good yield, thus leading to an improved synthesis of a series of (E)-1,2- diphenylethenes 3. The present approach provides a new solution to the inherent instability of aldehydes and also provides a direct access to C'C bond formation for the synthesis of 1,2-diphenylethenes from aryl aldehyde bisulfite adducts. Methods: All reactions were performed at 70-80o and the synthesized compounds were characterized by IR, 1H NMR, 13C NMR, and mass spectrometric techniques. Results: The present approach provides a new solution to the instability of aldehydes and also provides a direct access to C'C bond formation for the synthesis of 1,2-diphenylethenes from aryl aldehyde bisulfite adducts. Conclusion: In the present work, we have reported an efficient method for the synthesis of 1,2- diphenylethene derivatives. Aldehydes are commonly used as the starting materials in the McMurry reaction, which affords the stilbene derivatives, the core skeleton of various valuable compounds. To increase the stability of the aldehydes, bisulfite adducts are usually employed, but the deprotection process causes loss of process efficiency. To address this issue, we developed a method based on the single-pot reaction of aromatic bisulfite adduct using TiCl4/Zn in 1,4-dioxane.

Antituberculosis agents bearing the 1,2-disubstituted benzimidazole scaffold

Abstract: The emergence of drug-resistant strains in recent years has fueled the epidemic of tuberculosis. This necessitates the development of new chemical scaffolds to curb resistant tuberculosis for effective control of this disease. In this study, we have designed and synthesized two series of benzimidazole derivatives. Their antimycobacterial activities were initially evaluated using Mycobacterium tuberculosis H37RV strains. The most potent analog (6h) was further assessed using various drug-resistant M. tuberculosis strains. This report described the importance of benzimidazoles as new antitmycobacterial agents targeting both the M. tuberculosis H37RV as well as the drug-resistant-tuberculosis strains. The trifluoromethyl group which was essential for antimycobacterial activity was also highlighted. Graphical Abstract: Two series of benzimidazole derivatives and their antimycobacterial activities were evaluated using M. tuberculosis H37RV (MTB-H37RV) strains. Compound 6h was identified as the most potent among all synthesized compounds. The most potent analog was further assessed using various drug-resistant MTB strains. In addition, the trifluoromethyl was identified as an important substitution in giving good antimycobacterial effect. [InlineMediaObject not available: see fulltext.]

Synthesis of 3-Formylbenzenesulfonyl Chloride Derivatives

A synthetic route to 3-formylbenzenesulfonyl chloride derivatives from the corresponding benzaldehydes has been developed. The key step in this procedure is the conversion of aldehyde bisulfite adducts to target compounds via a two-stage reaction in the presence of Na 2 SO 4. A series of 3-formylbenzenesulfonyl chloride derivatives were prepared by this method and identified by chemical derivatization method.

Liquid-Liquid Extraction Protocol for the Removal of Aldehydes and Highly Reactive Ketones from Mixtures

The reaction of the bisulfite ion with aldehydes to form charged bisulfite adducts is a well-established method for the purification of aldehydes. This reaction has been modified to create a convenient liquid-liquid extraction method for the removal of aldehydes from mixtures. The use of a water-miscible solvent allows the reaction to occur during a simple 30 s shaking protocol by increasing the contact between the bisulfite ion and the aldehyde. The introduction of an immiscible solvent allows for the extraction of the uncharged organic components away from the bisulfite adduct. The developed protocol is applicable to a wide range of aldehydes, including sterically hindered neopentyl aldehydes. Sterically unhindered cyclic and linear ketones, as well as highly electrophilic ketones, are also removed using this protocol. The mild conditions tolerate a wide range of functional groups, allowing for excellent aldehyde contaminant removal rates with high levels of recovery of the desired component.

The Development of an Effective Synthetic Route of Belinostat

A practical synthetic route of belinostat is reported. Belinostat was obtained via a five-step process starting from benzaldehyde and including addition reaction with sodium bisulfite, sulfochlorination with chlorosulfonic acid, sulfonamidation with aniline, Knoevenagel condensation, and the final amidation with hydroxylamine. Key to the strategy is the preparation of 3-formylbenzenesulfonyl chloride using an economical and practical protocol. The main advantages of the route include inexpensive starting materials and acceptable overall yield. The scale-up experiment was carried out to provide 169 g of belinostat with 99.6% purity in 33% total yield.