57499-86-2

Usage

Uses

Used in Pharmaceutical Research:
1-(3,5-dinitro-benzoyl)-piperidine is used as a research compound for its potential applications in the development of new drugs targeting cancer and neurological disorders. Its unique chemical structure allows for exploration into various therapeutic avenues.
Used in Organic Synthesis:
In the field of organic chemistry, 1-(3,5-dinitro-benzoyl)-piperidine serves as a key intermediate in the synthesis of complex organic molecules. Its reactive nature and functional groups make it a valuable building block for creating novel compounds with specific biological activities.

Upstream product

• 110-89-4 piperidine 
• 99-33-2 3,5-dinitrobenoyl chloride 
• 1523-21-3 4-nitrophenyl 3,5-dinitrobenzoate 
• 100-02-7 4-nitro-phenol 
• 136367-45-8 2-chloro-4-nitrophenyl 3,5-dinitrobenzoate 
• 99-34-3 3,5-dinitrobenzoic acid 
• 59658-04-7 2-pyridyl 3,5-dinitrobenzoate 

Downstream Products

• 314047-34-2 (3,5-diaminophenyl)(piperidin-1-yl)methanone 

Relevant academic research and scientific papers

Design, Synthesis and in Vitro Tumor Cytotoxicity Evaluation of 3,5-Diamino-N-substituted Benzamide Derivatives as Novel GSK-3β Small Molecule Inhibitors

Glycogen synthase kinase-3 (GSK-3) plays an important regulatory role in various signaling pathways; such as PI3 K/AKT, which is closely related to the occurrence and development of tumors. At present, the most reported active GSK-3 inhibitors have the same structure: lactam ring or amide structure. To find out the GSK-3β small molecule inhibitor with novel, safe, efficient and more uncomplicated synthesis method, we analyzed in-depth reported crystal-binding patterns of GSK-3β small molecule inhibitor with GSK-3β protein, and designed and synthesized 17 non-reported 3,5-diamino-N-substituted benzamide compounds. Their structures were confirmed by 1H-NMR, 13C-NMR, and HR-MS. The preliminary screening of tumor cytotoxicity of compounds in vitro was detected by MTT, and their structure–activity relationships were illustrated. The results have shown that 3,5-diamino-N-[3-(trifluoromethyl)phenyl]benzamide (4d) exhibited significant tumor cytotoxicity against human colon cancer cells (HCT-116) with IC50 of 8.3 μm and showed commendable selectivity to GSK-3β. In addition, Compound 4d induced apoptosis to some extent and possessed modest PK properties.

Evidence for a catalytic six-membered cyclic transition state in aminolysis of 4-nitrophenyl 3,5-dinitrobenzoate in acetonitrile: Comparative Br?nsted-type plot, entropy of activation, and deuterium kinetic isotope effects

A kinetic study for reactions of 4-nitrophenyl 3,5-dinitrobenzoate (1a) with a series of cyclic secondary amines in acetonitrile is reported. Plots of the pseudo-firstorder rate constant (kobsd) vs [amine] curve upward, while those of kobs

Kinetic study on aminolysis of y-substituted-phenyl x-substituted- benzoates: Effects of substituents x and y on reactivity and reaction mechanism

A kinetic study on aminolysis of 2-chloro-4-nitrophenyl X-substituted-benzoates (2a-k) in 80 mol % H2O/20 mol % DMSO at 25.0 oC is reported. The Bronsted-type plot for the reactions of 2-chloro-4-nitrophenyl benzoate (2g) with a series of cyclic secondary amines curves downward (e.g., β1 = 0.25, β2 = 0.85 and pKa o = 10.3), which is typical of reactions reported to proceed through a stepwise mechanism with a change in ratedetermining step (RDS). The Hammett plot for the reactions of 2a-k with piperidine consists of two intersecting straight lines, while the corresponding Yukawa-Tsuno plot exhibits an excellent linear correlation with ρX = 1.15 and r = 0.59. Thus, it has been concluded that the nonlinear Hammett plot is not due to a change in RDS but is caused by stabilization of substrates through resonance interactions between the electron-donating substituent and the C=O bond. Substrates possessing a substituent at the 2-position of the leaving aryloxide deviate negatively from the curved Bronsted-type plot for the reactions of Y-substituted-phenyl benzoates (3ai), implying that the steric hindrance exerted by the substituent at the 2-position is an important factor which governs the reactivity of Y-substituted-phenyl benzoates.

Kinetic study on aminolysis of 2-chloro-4-nitrophenyl x-substituted-benzoates in acetonitrile and in H2O Containing 20mol% DMSO: Effects of medium and substituent X on reactivity and reaction mechanism

Second-order rate constants for reactions of 2-chloro-4-nitrophenyl X-substituted-benzoates 1a-1j with a series of cyclic secondary amines in MeCN have been measured. Comparison of the kinetic results with those reported previously for the corresponding reactions carried out in H2O containing 20 mol % DMSO has revealed that amines are less reactive in MeCN. The Bronsted-type plot for the aminolysis of 2-chloro-4-nitrophenyl benzoate (1f) in MeCN is linear with βnuc= 0.64, which is in contrast to the curved Bronsted-type plot reported for the reaction performed in the H2O-DMSO misxture. The Hammett plot for the reactions of 1a-1j with piperidine consists of two intersecting straight lines while the Yukawa-Tsuno plot exhibits an excellent linear correlation with ρX= 1.22 and r = 0.60, indicating that the nonlinear Hammett plot is not due to a change in rate-determining step but is caused by stabilization of substrates possessing an electron-donating substituent through resonance interactions between the substituent and the carbonyl functionality. It has been concluded that medium change from the H2O-DMSO mixture to MeCN forces the aminolysis of 1a-1j to proceed through a concerted mechanism by destabilizing the zwitterionic tetrahedral intermediate (T±).

Comparison of aminolysis of 2-pyridyl and 4-pyridyl x-substituted benzoates in acetonitrile: Evidence for a concerted mechanism involving a cyclic transition state

A kinetic study on reactions of 2-pyridyl X-substituted benzoates (6a-i) with a series of cyclic secondary amines in MeCN is reported. The Hammett plot for the reaction of 6a-i with piperidine consists of two intersecting straight lines while the Yukawa-Tsuno plot exhibits an excellent linear correlation with ρX = 1.28 and r = 0.63, indicating that the nonlinear Hammett plot is not caused by a change in the rate-determining step but rather by resonance stabilization of substrates possessing an electron-donating group (EDG) in the benzoyl moiety. The Bronsted-type plots are linear with βnuc = 0.59 ± 0.02, which is typical of reactions reported to proceed through a concerted mechanism. A cyclic transition state (TS), which forces the reaction to proceed through a concerted mechanism, is proposed. The deuterium kinetic isotope effect of 1.3 ± 0.1 is consistent with the proposed mechanism. Analysis of activation parameters reveals that ΔH? increases linearly as the substituent X changes from an electron-withdrawing group (EWG) to an EDG, while TΔS ? remains nearly constant with a large negative value. The constant TΔS? value further supports the proposal that the reaction proceeds through a concerted mechanism with a cyclic TS.

Aminolysis of Y-substituted-phenyl 2-methoxybenzoates in acetonitrile: Effect of the o-methoxy group on reactivity and reaction mechanism

Second-order rate constants (kN) were measured for aminolyses of Y-substituted-phenyl 2-methoxybenzoates 2a-i and 4-nitrophenyl X-substituted-benzoates 3a-j in MeCN at 25.0 °C. The Bronsted-type plot for the reactions of 2a-i with piperidine curves downward, indicating that a change in rate-determining step (RDS) occurs. The Hammett plot for the reactions of 3a-j with piperidine consists of two intersecting straight lines, which might be taken as evidence for a change in RDS. However, the nonlinear Hammett plot has been suggested not to be due to a change in RDS but rather to the stabilization of the ground state of substrates possessing an electron-donating group (EDG) (e.g., 3a-c) through a resonance interaction, since the corresponding Yukawa-Tsuno plot exhibits an excellent linear correlation with ρ = 0.54 and r = 1.54. The ρ value found for the reactions of 3a-j in MeCN is much smaller than that reported previously for the corresponding reactions in H2O (i.e., ρ = 0.75). It is proposed that the reactions of 3a-j in MeCN proceed through a forced concerted mechanism due to instability of T± in the aprotic solvent, while the reactions of 2a-i proceed through a stepwise pathway with a stabilized T ± through an intramolecular H-bonding interaction.

Structure-reactivity correlations in nucleophilic substitution reactions of Y-substituted phenyl X-substituted benzoates with anionic and neutral nucleophiles

A kinetic study is reported for the reactions of 4-nitrophenyl X-substituted benzoates (1a-l) and Y-substituted phenyl benzoates (2a-l) with two anionic nucleophiles (OH- and CN-) and three amines (piperidine, hydrazine, and glycylglycine) in 80 mol% H2O-20 mol% dimethyl sulfoxide (DMSO) at 25.0 ± 0.1 °C. Each Hammett plot exhibits two intersecting straight lines for the reactions of 1a-l with the anionic nucleophiles and piperidine, while the Yukawa-Tsuno plots for the same reactions are linear. The Hammett plots for the reactions of 2a-l with hydrazine and glycylglycine demonstrate much better linear correlations with σ- constants than with σ° or σ constants, indicating that the leaving group departure occurs at the rate determining step (RDS). On the contrary, σ- constants result in poorer Hammett correlation than σ° constants for the corresponding reactions with OH- and CN-, indicating that the leaving group departure occurs after the RDS for the reactions with the anionic nucleophiles. The large ρX value (1.7 ± 0.1) obtained for the reactions of 1a-l with the anionic nucleophiles supports the proposal that the reactions proceed through an addition intermediate with its formation being the RDS. The Royal Society of Chemistry 2006.