42792-81-4

Upstream product

• 108-94-1 cyclohexanone 
• 99-61-6 3-nitro-benzaldehyde 
• 874-23-7 2-acetylcyclohexanone 
• 6651-36-1 1-(Trimethylsilyloxy)cyclohexene 
• 29949-19-7 1,1-diacetoxy-1-(3-nitrophenyl)methane 
• 917-64-6 methyl magnesium iodide 
• 108-93-0 cyclohexanol 

Downstream Products

• 282724-29-2 (2E,6E)-2,6-bis(3-aminobenzylidene)cyclohexanone 
• 127249-00-7 2,6-Bis-<(3-aminophenyl)-methylen>-cyclohexanon 
• 1222559-16-1 C₃₁H₂₅N₃O₇ 

Relevant academic research and scientific papers

Bi-functional modified-phosphate catalyzed the synthesis of α-α′-(EE)-bis(benzylidene)-cycloalkanones: Microwave versus conventional-heating

The impregnation of hydroxyapatite (HAP) by NaNO3 leads to a modified-hydroxyapatite which has a bi-functional acid-base property. Sodium-modified-hydroxyapatite (Na-HAP) efficiently catalyzed the cross-aldol condensation of arylaldehydes and cycloketones to afford α-α′- (EE)-bis(benzylidene)-cycloalkanones in good yields under microwave irradiation. Moreover, the methodology described in this paper provides a very easy and efficient synthesis carried out in water as the greenest available solvent under conventional heating. A comparison study between these two different modes of heating was investigated. The catalyst was easily recovered and efficiently re-used.

Green, rapid, and highly efficient syntheses of α,α′-bis[(aryl or allyl)idene]cycloalkanones and 2-[(aryl or allyl)idene]-1-indanones as potentially biologic compounds via solvent-free microwave-assisted Claisen–Schmidt condensation catalyzed by MoCl5

A new, green, and highly efficient protocol for the expeditious preparation of some α,α′-bis[(aryl or allyl)idene]cycloalkanones and 2-[(aryl or allyl)idene]-1-indanones via a simple microwave-assisted Claisen–Schmidt condensation reaction catalyzed by MoCl5 was successfully developed. Outstanding features of the current methodology include the use of solvent-free conditions, simple operation, use of a very inexpensive and available catalyst, low catalyst loading, short reaction times, high yields of the pure products, no harmful by-products, easy workup, and also the applicability of microwave irradiation as a clean source of energy. Furthermore, a gram-scale reaction was successfully conducted, proving the scalability of this current Claisen–Schmidt condensation reaction.

Synthesis of diarylidenecyclohexanone derivatives as potential anti-inflammatory leads against COX-2/mPGES1 and 5-LOX

Inflammation is a pathophysiological condition which progresses through the prostaglandin (PG) and leukotriene (LT) pathways channelized by the enzymes COX/mPGES1 and 5-LOX respectively. Diarylidenecyclohexanone (DAC) derivatives (Ia-j, IIa-c, IIIa and IVa) were synthesized, characterized and screened for their in vitro anti-inflammatory activity via inhibition of 5-LOX and COX-2/mPGES1 enzymes. Compound Ic inhibited PGE2 production exhibiting an IC50 of 6.7 ± 0.19 μM, comparable to the standard inhibitor, licofelone (IC50 of 5.4 ± 0.02 μM). Compounds Ie and Ig showed maximum in vitro inhibitory activity against 5-LOX, exhibiting an IC50 of 1.4 ± 0.1 μM and 1.5 ± 0.13 μM, respectively, and these are comparable to that of the standard drug, zileuton (IC50 = 1.2 ± 0.11 μM). Ie and Ig do not possess radical scavenging properties and may not be disrupting the redox cycle of the enzyme. Hence they may be inhibiting the enzyme by a competitive mode. One of the compounds in the DAC series (IIc) containing a heterocyclic thienyl ring inhibited all the three enzymes. It inhibited 5-LOX and COX-2/mPGES1 with an IC50 of 1.8 ± 0.12 μM and 7.5 ± 0.4 μM respectively. An RT-PCR based mRNA expression study highlighted that Ic predominantly inhibited the expression of COX-2 rather than mPGES1. No toxicity towards the HeLa cell line indicated that the DACs could serve as structural templates towards lead optimization of compounds for discovery of novel, potent, safe and affordable drugs as anti-inflammatory agents.

Synthesis, characterization, crystal structure of novel bis-thiomethylcyclohexanone derivatives and their inhibitory properties against some metabolic enzymes

In this study, a series of novel bis-thiomethylcyclohexanone compounds (3a–3j) were synthesized by the addition of thio-Michael to the bis-chalcones under mild reaction conditions. The bis-thiomethylcyclohexanone derivatives (bis-sulfides) were characterized by 1H NMR, 13C NMR, FTIR and elemental analysis techniques. Furthermore, the molecular and crystal structures of 3h, 3i and 3j compounds were determined by single crystal X-ray diffraction studies. In this study, X-ray crystallography provided an alternative and often-complementary means for elucidating functional groups at the enzyme inhibitory site. Acetylcholinesterase (AChE) is a member of the hydrolase protein super family and has a significant role in acetylcholine-mediated neurotransmission. Here, we report the synthesis and determining of novel bis-thiomethylcyclohexanone compounds based hybrid scaffold of AChE inhibitors. The newly synthesized bis-thiomethylcyclohexanone compounds showed Ki values of in range of 39.14–183.23 nM against human carbonic anhydrase I isoenzyme (hCA I), 46.03–194.02 nM against human carbonic anhydrase II isoenzyme (hCA II), 4.55–32.64 nM against AChE and 12.77–37.38 nM against butyrylcholinesterase (BChE). As a result, novel bis-thiomethylcyclohexanone compounds can have promising anti Alzheimer drug potential and record novel hCA I, and hCA II enzymes inhibitor.

Syntheses and X-ray crystal structures combined with conformational and Hirshfeld analyses of chalcones based on a cyclohexanone scaffold

Four chalcone structures based on cyclohexanone cores were presented. The structures of bis-benzylidenecyclohexanone analogs 3a-d were elucidated using spectrophotometric and single-crystal X-ray techniques. Compounds 3a, 3b, and 3d crystalized in the monoclinic crystal system with the space group P21/c. However, 3c crystalized in the orthorhombic system with the space group Pna21. A set of computational studies related to the structures were carried out. Using the B3LYP method and the 6-31G(d,p) basis set, the molecular structures of the studied dienones were optimized, followed by the evaluation of their electronic properties and UV–vis spectra. The bond distances and angles well-correlated with the experimental data. All the dienones were stabilized by C–H?O intramolecular H-bonding interactions. The presence of two Cl atoms at the ortho-position of each phenyl ring in 3c caused steric hinderance with the cyclohexanone ring, leading to the weakest H?O interactions among the studied compounds. The TD-DFT method was used to assign and explain the origin of the electronic spectra of the studied dienones.

Hydroxyl-substituted double Schiff-base condensed 4-piperidone/cyclohexanones as potential anticancer agents with biological evaluation

Novel hydroxyl-substituted double Schiff-base 4-piperidone/cyclohexanone derivatives, 3a–e, 4a–e, 5a–d, and 6a–c, were synthesized and fully characterized by 1H NMR, IR and elemental analysis. The cytotoxicity against human carcinoma cell lines

Synthesis, mechanistic and synergy studies of diarylidenecyclohexanone derivatives as new antiplasmodial pharmacophores

Diarylidenecyclohexanone (DAC) derivatives (Ia-i, IIa-c and IIIa-b) were synthesized, characterized and screened for their invitro antiplasmodial activities against erythrocytic stages of chloroquine (CQ) sensitive and resistant strains of P. falciparum by using SYBR green I fluorescence assay. SAR studies of DAC derivatives showed antiplasmodial activity in the order of 3-NO2 (Ib, IC50 0.95 μM) > 3-chloro (Id, IC50 3 μM) > 4-chloro (Ie, IC50 8.5 μM) > 2-chloro (Ic, IC50 13 μM). Further Ib and Id exhibited nearly equal potencies against CQ-resistant strains P. falciparum Dd2, {IC50 1 μM (Ib) and 2.7 μM (Id)} and PfINDO {IC50 1.1 μM (Ib) and 2.5 μM (Id)}. Drug exposure followed by drug withdrawal-based stage-specific kill kinetic studies showed that Ib is shizonticidal within 3 h while the earliest killing actions against Trophozoites and Rings were seen at >3 h and >6 h, respectively. Combination studies of the most potent leads viz. Ib and Id showed strong to moderate synergistic effects with Artemisinin (?FIC50: 0.34 to 0.63) whereas no interaction (?FIC50: 0.65 to 2.36) was observed with Chloroquine. The DACs showed significant insilico binding affinity with β-haematin and P. falciparum lactate dehydrogenase (PfLDH) suggesting these to be the targets of their antiplasmodial action. High compliance with Lipinski rule of 5 and high selectivity index of Ib (105.3) and Id (8.3) against HeLa cell line indicated that Diarylidenecyclohexanones could serve as structural templates towards lead optimization of compounds for discovery of novel, potent, safe and affordable drugs against malaria.

An efficient green approach to aldol and cross-aldol condensations of ketones with aromatic aldehydes catalyzed by nanometasilica disulfuric acid in water

Aldol and cross-aldol condensations of aromatic aldehydes with various ketones in the presence of nanometasilica disulfuric acid (NMSDSA) as heterogeneous catalyst are presented. The catalyst was prepared according to the developed earlier method using inexpensive and readily available starting materials. The highly active catalyst gave excellent yields of the desired aldol products without self-condensation reaction taking place. Reaction times were short, the procedure and work-up were simple, and no volatile or hazardous organic solvents were involved. The catalyst could be recovered three times with only slight reduction in activity.

Design, characterization, and use of N,N-diethyl-N-sulfoethanaminium hydrogen sulfate {[Et3N-SO3H]HSO4} as a novel and highly efficient catalyst for preparation of α,α′-bis(arylidene)cycloalkanones

Abstract: The aim of this work is to introduce a novel and attractive protic acidic ionic liquid as catalyst for organic synthesis. To achieve this aim, N,N-diethyl-N-sulfoethanaminium hydrogen sulfate {[Et3N-SO3H]HSO4} was prepared by reaction of NEt3 with ClSO3H and then with H2SO4. The novel acidic ionic liquid was identified by Fourier-transform infrared (FT-IR), 1H nuclear magnetic resonance (NMR), 13C NMR, and mass spectroscopies. Its catalytic activity was then examined in the cross-aldol condensation reaction of arylaldehydes with cycloalkanones under solvent-free conditions, obtaining α,α′-bis(arylidene)cycloalkanones in high yield after short reaction time. Graphical Abstract: [Figure not available: see fulltext.]

Synthesis of air-stable mixed bis-carboxylate titanocene complexes and their catalytic behaviors in cross-aldol and Mannich reactions

Tunable organometallic Lewis acid catalysts were developed by combining salicylic acid (H2-Sal) with benzoic acid (H-Ben), 4-fluorobenzoic acid (H-BenF) and 3-thiophenic acid (H-Th), as coligands for mixed bis-carboxylate titanocene complexes. Three air-stable complexes [Cp2Ti(η1-HSal)(η1-Ben)] (1), [Cp2Ti(η1-HSal)(η1-BenF)] (2) and [Cp2Ti[η1-HSal][(η1-Th)] (3) were prepared in high yields by the reaction of salicylato titanocene chelate with carboxylate ligands. The mixed bis-carboxylate titanocene complexes were fully characterized by physicochemical and spectroscopic methods. Single-crystal X-ray diffraction studies revealed Ti–O(H-Sal) bond distances in 1, 2 and 3 of 1.972(3), 1.9245(18) and 1.912(5)??, respectively, while the bond distances involving the coligands of 1, 2 and 3 are 1.908(3)?? (Ti–OBen), 1.9296(19)?? (Ti–OBenF) and 1.945(5)?? (Ti–OTh), respectively. These bis-carboxylate titanocene complexes showed satisfactory activities and selectivities in Mannich and cross-aldol reactions. Notably, complex 3 bearing the labile thiophene carboxylate ligand gave high yields with a diastereomer ratio (d.r.) as high as 1:99 for the direct Mannich reactions of benzaldehyde, cyclohexanone and aniline. In cross-aldol reaction of benzaldehyde and cyclohexanone, 1 and 2 successfully catalyzed the formation of double-aldol products in up to 99?% yield.