34907-24-9

Upstream product

• 22661-28-5 N-(4-nitro-benzyl)-benzaldoxime 
• 108-24-7 acetic anhydride 
• 1485-70-7 N-benzylbenzamide 
• 555-16-8 4-nitrobenzaldehdye 
• 100-47-0 benzonitrile 
• 98-88-4 benzoyl chloride 
• 18600-42-5 4-nitrobenzylamine hydrochloride 
• 23405-15-4 benzoic acid N-hydroxysuccinimide ester 
• 7409-30-5 p-nitrobenzylamine 
• 65-85-0 benzoic acid 
• 619-90-9 4-nitrobenzyl acetate 
• 100-11-8 1-bromomethyl-4-nitro-benzene 
• 455-32-3 benzoyl fluoride 
• 619-73-8 4-nitrobenzyl chloride 

Downstream Products

• 36038-92-3 N-(4-nitrobenzyl)benzimidoyl chloride 
• 32478-52-7 N-p-α-Naphthylazobenzyliden-4-biphenylamin 
• 32479-27-9 N-benzamid 
• 32478-57-2 N-benzamid 
• 32479-30-4 N-benzamid 
• 32479-28-0 N-benzamid 
• 32478-72-1 N-benzamid 
• 32478-91-4 N-Benzyliden-p-benzamidomethyl-anilin 
• 14429-16-4 benzyl(4-nitrobenzyl)amine 
• 41859-85-2 N-benzoyl-4-hydroxybenzylamine 
• 39057-66-4 N-benzoyl-4-nitrobenzamide 
• 32478-65-2 N-(4'-Aminobenzyl)benzamide 

Relevant academic research and scientific papers

FeCl2·4H2O catalyzed ritter reaction with nitriles and halohydrocarbons

An efficient and inexpensive synthesis of N-substituted amides from the Ritter reaction of nitriles with various halohydrocarbons catalyzed by FeCl2·4H2O is described. FeCl2·4H2O economically efficiently catalyzed the Ritter reaction under solvent-free conditions. A range of halohydrocarbons (benzyl, tert-butyl and sec-alkyl halohydrocarbons) were coupled with nitriles to provide the corresponding amides in high to excellent yields.

Convenient synthesis of amides by Zn(ClO4)2·6H2O catalysed Ritter reaction with nitriles and halohydrocarbons

A convenient and high yielding procedure for the synthesis of amides by the Ritter reaction of nitriles and halohydrocarbons in the presence of Zn(ClO4)2·6H2O as a highly stable, effective and available catalyst is described.

Fe(ClO 4) 3 ·h 2 O-Catalyzed Ritter Reaction: A Convenient Synthesis of Amides from Esters and Nitriles

An efficient and inexpensive synthesis of N-substituted amides from the Ritter reaction of nitriles with esters catalyzed by Fe(ClO 4) 3 ·H 2 O is described. Fe(ClO 4) 3 ·H 2 O is an economically efficient catalyst for the Ritter reaction under solvent-free conditions. Reactions of a range of esters (benzyl, sec-alkyl, and tert-butyl esters) with nitriles (primary, secondary, tertiary, and aryl nitriles) were performed to provide the corresponding amides in high to excellent yields.

Sulfur–Fluoride Exchange (SuFEx)-Mediated Synthesis of Sterically Hindered and Electron-Deficient Secondary and Tertiary Amides via Acyl Fluoride Intermediates

Amide bond formation is one of the most executed reactions in chemistry and biology. This is largely due to the ubiquity of the amide functional group in biological molecules, natural products and pharmaceutically important drugs. We report here the development of “SuFExAmide”: a new sulfur–fluoride exchange (SuFEx) click chemistry based protocol for the efficient amidation of carboxylic acids via acyl fluoride intermediates. We have developed benzene-1,3-disulfonyl fluoride as a cost effective, powerful and versatile coupling agent, which delivers challenging secondary and tertiary amides in excellent yields from sterically hindered and electron-deficient amines. The straightforward method offers significant benefits over existing protocols in terms of substrate scope, efficiency and ease of operation and is demonstrated by the synthesis of 44 amides, including GNF6702, an antiprotozoal drug candidate. In the majority of cases, the amide products are obtained in high yield without the need for excess reagents or chromatographic purification.

Synthesis and Biological Evaluation of 2-Aminobenzothiazole and Benzimidazole Analogs Based on the Clathrodin Structure

A series of 2-aminobenzothiazole and benzimidazole analogs based on the clathrodin scaffold was synthesized and investigated for their antimicrobial and antiproliferative activities as well as for their effects in hepatitis C virus (HCV) replicon model. Compound 7, derived from 2-aminobenzothiazole, exhibited moderate antimicrobial activity only against the Gram-positive bacterium, Enterococcus faecalis. In the antiviral assay, compounds 4d and 7 were found to suppress the HCV replicon by >70%, but also to exhibit cytotoxicity against the host cells (35 and 44%, respectively). Compounds 4a and 7 demonstrated good activity in the antiproliferative assays on the human melanoma cell line A-375. To assess the selectivity of the effects between cancerous and noncancerous cells, a mouse fibroblast cell line was used. The IC50 values for compound 7 against the melanoma cell line A-375 and the fibroblast cell line BALB/c 3T3 were 16 and 71 μM, respectively, yielding fourfold selectivity toward the cancer cell line. These results suggest that compound 7 should be studied further in order to fully explore its potential for drug development. A series of novel 2-aminobenzothiazole and benzimidazole derivatives based on the clathrodin structure was synthesized and evaluated for antimicrobial, antiproliferative and antiviral activities. (9H-Fluoren-9-yl)-methyl [(2-aminobenzo[d]thiazol-6-yl)methyl]carbamate 7 exhibited antiproliferative activity against the melanoma cell line A-375 (IC50 = 16 μM) with 4-fold selectivity between cancerous (A-375) and noncancerous (BALB/c 3T3) cells.

Direct synthesis of amides from coupling of alcohols and amines catalyzed by ruthenium(II) thiocarboxamide complexes under aerobic conditions

Four octahedral ruthenium(II) thiocarboxamide complexes of the general formula [RuClCO(AsPh3)2(L)] (L = N-substituted pyridine-2-thiocarboxamide) incorporating carbonyl and triphenylarsine have been synthesized from the reaction of 1 equiv of ruthenium precursor [RuHClCO(AsPh3)3] with 1 equiv of thiocarboxamide ligands in refluxing ethanol in the presence of base. All the new complexes have been fully characterized by means of elemental analysis, IR, UV-vis, and NMR spectral methods. Molecular structures of all the complexes were determined by X-ray crystallography, which confirm the coordination mode of thiocarboxamide and reveal the presence of a distorted octahedral geometry around the Ru ion. All the ruthenium(II) thiocarboxamide complexes were generated as highly efficient catalysts for synthesis of secondary or tertiary amides by coupling of amines and alcohols with low catalyst loading, and the maximum yield was obtained up to 97%. The coupling reaction can be readily carried out under mild aerobic conditions, and release of water is the only byproduct. Further, the effect of substituents of the ligand, solvents, reaction temperature, time, and catalyst loading on the catalytic activity of the complexes has been investigated. A plausible mechanism is proposed for the synthesis of amides via hemiaminal as intermediate through an oxidation of an alcohol to aldehyde.

Substituent effect on exo stereoselectivity in the 1,3-dipolar cycloaddition reaction of tulipalin A with nitrile ylides

(Chemical Equation Presented) 1,3-Dipolar cycloaddition reactions of dihydro-3-methylene-2(3H)-furanone (tulipalin A) with various benzonitrile(p-X-benzylide) ylides prefer formation of exo-cycloadducts in the extent corresponding to an increasing electron donor character of the substituent X in the para-position of the benzylide phenyl ring of the 1,3-dipolar reagent. The substituent effect on diastereoselectivity of the 1,3-DC reaction is rationalized in terms of CH/π interaction between the dipole and the dipolarophile in an exo-transition state. The determining role of such an interaction is demonstrated by the correlation of the observed diastereoselectivities with substituent Hammett σ constants, which shows a small negative ρ value. A certain contribution of CO/π interaction between the lactone carbonyl and the substituted phenyl ring to mediation of the substituent effect is also discussed. The energy profiles of both reaction pathways were analyzed using DFT and RI-MP2 theoretical approaches. Calculated energy and structural differences between located transition states are consistent with reaction diastereoselectivities.

Structure-based design and synthesis of the first weak non-phosphate inhibitors for IspF, an enzyme in the non-mevalonate pathway of isoprenoid biosynthesis

In this paper, we describe the structure-based design, synthesis, and biological evaluation of cytosine derivatives and analogues that inhibit IspF, an enzyme in the non-mevalonate pathway of isoprenoid biosynthesis. This pathway is responsible for the biosynthesis of the C5 precursors to isoprenoids, isopentenyl diphosphate (IPP, 1) and dimethylallyl diphosphate (DMAPP, 2; Scheme 1). The non-mevalonate pathway is the sole source for 1 and 2 in the protozoan Plasmodium parasites. Since mammals exclusively utilize the alternative mevalonate pathway, the enzymes of the non-mevalonate pathway have been identified as attractive new drug targets in the fight against malaria. Based on computer modeling (cf. Figs. 2 and 3), new cytosine derivatives and analogues (Fig. 1) were selected as potential drug-like inhibitors of IspF protein, and synthesized (Schemes 2-5). Determination of the enzyme activity by 13C-NMR spectroscopy in the presence of the new ligands showed inhibitory activities for some of the prepared cytosine and pyridine-2,5-diamine derivatives in the upper micromolar range (IC50 values; Table). The data suggest that it is possible to inhibit IspF protein without binding to the polar diphosphate binding site and the side chain of Asp56′, which interacts with the ribose moiety of the substrate and substrate analogues. Furthermore, a new spacious sub-pocket was discovered which accommodates aromatic spacers between cytosine derivatives or analogues (binding to 'Pocket III') and rings that occupy the flexible hydrophobic region of 'Pocket II'. The proposed binding mode remains to be further validated by X-ray crystallography.

Synthesis of bis(2,4-diarylimidazol-5-yl) diselenides from N-benzylbenzimidoyl isoselenocyanates

The reaction of N-benzylbenzamides 6 with SOCl2 under reflux gave the corresponding N-benzylbenzimidoyl chlorides 7. Further treatment with KSeCN in dry acetone yielded imidoyl isoselenocyanates 3 (Scheme 2). These compounds, obtained in satisfying yields, proved to be stable enough to be purified and analyzed. Reaction of 3 with morpholine in dry acetone led to the corresponding selenourea derivatives 8. On treatment with Et3N, the 4-nitrobenzyl derivatives of type 3 were transformed into bis(2,4-diarylimidazol-5-yl) diselenides 9 (Scheme 3). This transformation takes place only when the benzyl residue bears an NO2 group and the phenyl group is not substituted with a strong electron-donating group. A reaction mechanism for the formation of 9 is proposed in Scheme 4. The key structures have been established by X-ray crystallography.

AMIDINE DERIVATIVES WITH NITRIC OXIDE SYNTHETASE ACTIVITIES

Amidine derivative compounds of formula I as defined in the Specification having nitric oxide synthetase inhibitory activity as well as processes for the preparation of and compositions containing said compounds are described