18989-82-7

Basic information

• Product Name: 2,6-bis(4-chlorobenzylidene)cyclohexan-1-one
• Synonyms: 2,6-bis(4-chlorobenzylidene)cyclohexan-1-one;1,3-Bis(4-chlorobenzylidene)cyclohexane-2-one;2,6-Bis(4-chlorobenzylidene)cyclohexane-1-one;2,6-Bis(p-chlorobenzylidene)cyclohexanone;2,6-Bis[(4-chlorophenyl)methylene]cyclohexanone;2,6-Bis(4-chlorobenzylidene)cyclohexanone;Cyclohexanone, 2,6-bis((4-chlorophenyl)methylene)-;Einecs 242-725-7
• CAS NO: 18989-82-7
• Molecular Formula: C₂₀H₁₆Cl₂O
• Molecular Weight: 343.24644
• EINECS: 242-725-7
• Mol File: 18989-82-7.mol

Chemical Properties

• Melting Point: 147-148 °C
• Boiling Point: 528.7°Cat760mmHg
• Flash Point: 220.4°C
• Appearance: /
• Density: 1.308g/cm³
• Vapor Pressure: 2.91E-11mmHg at 25°C
• Refractive Index: 1.677
• CAS DataBase Reference: 2,6-bis(4-chlorobenzylidene)cyclohexan-1-one(CAS DataBase Reference)
• NIST Chemistry Reference: 2,6-bis(4-chlorobenzylidene)cyclohexan-1-one(18989-82-7)
• EPA Substance Registry System: 2,6-bis(4-chlorobenzylidene)cyclohexan-1-one(18989-82-7)

Safety Data

• Hazardous Substances Data: 18989-82-7(Hazardous Substances Data)

Usage

Uses

Used in Perfumery:
2,6-bis(4-chlorobenzylidene)cyclohexan-1-one is used as a base note in perfumery for its long-lasting and animalic scent, which is sweet, woody, and musky. Its intense fragrance contributes to the depth and complexity of high-end perfumes and colognes.
Used in Pharmaceutical Research:
2,6-bis(4-chlorobenzylidene)cyclohexan-1-one is studied for its potential pharmaceutical properties, indicating that it may have applications in the development of new drugs or treatments.
Used in Flavoring Agents:
In the food and beverage industry, 2,6-bis(4-chlorobenzylidene)cyclohexan-1-one is used as a flavoring agent, adding unique taste profiles to various products.

InChI:InChI=1/C20H16Cl2O/c21-18-8-4-14(5-9-18)12-16-2-1-3-17(20(16)23)13-15-6-10-19(22)11-7-15/h4-13H,1-3H2

Upstream product

• 1670-47-9 1,1-diethoxycyclohexane 
• 104-88-1 4-chlorobenzaldehyde 
• 108-94-1 cyclohexanone 
• 6651-36-1 1-(Trimethylsilyloxy)cyclohexene 
• 13086-93-6 (acetyloxy)(4-chlorophenyl)methyl acetate 

Downstream Products

• 1383970-05-5 (E)-2-(4-bromophenyl)-7-(4-chlorobenzylidene)-3-(4-chlorophenyl)-3,3a,4,5,6,7-hexahydro-2H-indazole 
• 110049-85-9 2,6-bis(4-chlorobenzyl)cyclohexanone 
• 1027003-73-1 9-(4-chlorophenylmethylene)-5-(4-chlorophenyl)-2-thioxo-2,3,6,7,8,9-hexahydropyrimido[4,5-b]quinolin-4(1H)-one 
• 1224967-22-9 3-(4-chlorobenzylidene)-7-(4-chlorophenyl)-3,4,5,6-tetrahydroquinolino[2'',3'':4',5']pyrimido[2',1':2,3]thiazolo[4,5-b]quinoxalin-8-one 
• 94990-32-6 8-(4-chlorobenzylidene)-4-(4-chlorophenyl)-5,6,7,8-tetrahydroquinazolin-2-ylamine 
• 94990-32-6 E-2-amino-4-(4-chlorophenyl)-8-(4'-chlorophenylmethylene)-5,6,7,8-tetrahydrobenzo[d]pyrimidine 
• 178946-89-9 bis(3-indolyl)-4-chlorophenylmethane 

Relevant articles and documents

Design, synthesis and antimicrobial properties of novel 3,3a,4,5,6,7-hexahydroindazole and arylthiazolylpyrazoline derivatives

A remarkable diastereoselective synthesis of some novel arylthiazolyl pyrazoline derivatives 3(a-l) is displayed which were evaluated for their in vitro antimicrobial activities. In particular, compounds 3e, 3g & 3l (MIC 12.5 μg /ml) showed good activity against S. aureus and compounds 3b & 3j (MIC 12.5 μg / ml) against B. subtilis. Compounds 3g, 3i, 3j (MIC 12.5 μg/ ml) and 3l (MIC 6.25 μg / ml) also displayed excellent antifungal activity against C. albicans. Of all the synthesized compounds, 3g and 3e exerted a wide range of antibacterial activities against entire tested gram positive (S. aureus and B. subtilis) and gram negative (E. coli and P. aeruginosa) bacterial strain except P. aeruginosa.

Activated charcoal-mediated synthesis of chalcones catalyzed by NaOH in water

A variety of chalcones were synthesized in good yields by the activated charcoal-mediated aldol reactions between benzaldehydes and acetophenones catalyzed by NaOH in water. 2,6-Bis((E)-benzylidene)cyclohexan-1-ones were prepared by the aldol reactions between benzaldehydes and cyclohexanone. Activated charcoal could be recycled five times without the significant decrease of yields.

Synthesis of thiazolylidenethiazoloquinazolinone hybrids from monocarbonyl curcumin analogues. Characterization, bio-evaluation and DFT study

Given the diverse pharmacological attributes possessed by the curcumin and its analogs, quinazolinethione 3, thiazoloquinazolinone 4, and thiazolylidene thiazoloquinazolinone hybrids D1-D12 were synthesized from α, α’ Bis(arylidene)Cyclohexanone (BAC) as starting material. The proposed structures of all synthesized compounds were confirmed by 1H, 13CNMR, and elemental analysis. The newly synthesized hybrids were screened in vitro for their antimicrobial and antioxidant activities. Preliminary studies showed that compounds D4, D5, D10, D11, and D12 exhibited superior inhibitory behaviors against some microorganisms in comparison with standard drugs. In addition, DPPH radical scavenging assay was used to evaluate their antioxidant property. Accordingly, compound D11 was found to be a more powerful antioxidant than the other compounds. Furthermore, the HOMO–LUMO energy values and some chemical parameters indicate that the synthesized hybrid D11 is more reactive than D7. These results were consistent with our experimental data on antioxidants. Moreover, molecular electrostatic potential (MEP) maps were computed in order to predict the reactive sites for nucleophilic and electrophilic attacks of the synthesized hybrids D7 and D11.

Synthesis and characterization of functionalized NaP Zeolite@CoFe2O4 hybrid materials: a micro–meso-structure catalyst for aldol condensation

In this work, magnetic nanocomposite of NaP Zeolite and CoFe2O4 as magnetic nanoparticles (MNP’s) with different ratios were prepared and in the second step functionalized with 2-aminopyridine as a basic group. All samples were characterized by FT-IR, XRD, VSM, FESEM, EDX, TEM, and BET and thermal analyses. The results show that CoFe2O4 MNP’s was dispersed on NaP Zeolite without any significant aggregation with particle size about 30–50?nm. The BET and TEM confirmed the presence of mesoporous phase in the surface of NaP Zeolite/CoFe2O4 and preparation a micro–meso-structure. The NaP Zeolite/CoFe2O4 and NaP Zeolite/CoFe2O4/Am-Py were used as acid–base catalysts for aldol condensation of cyclohexanone with benzaldehyde, and furfural with acetone which produce curcumin and biofuel intermediates, respectively, in solvent-free condition. The effect of different factors such as the percent of CoFe2O4 MNP’s, catalyst amount, solvent, time and temperature was investigated. The catalyst was easily separated with an external magnet and reused four times without significant change in the yield. These catalysts have various advantages including high loading capacity, low leaching for CoFe2O4 MNP’s and simple and efficient recovery procedure which can be used under mild and ecofriendly condition.

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.

Antiparasitic activity of synthetic curcumin monocarbonyl analogues against Trichomonas vaginalis

Trichomoniasis is a parasitic infection caused by Trichomonas vaginalis and it is considered to be the most common non-viral sexually transmitted infection in the world. Since the 1960s, nitroimidazoles such as metronidazole are the drugs of choice for the treatment of trichomoniasis, but many adverse effects and allergic reactions may result from their use. Reports of metronidazole-resistant infections also highlight the importance for the search of new anti-T. vaginalis agents. Considering this, herein we report the anti-T. vaginalis evaluation of 21 synthetic monocarbonyl analogues of curcumin, which itself has been reported to possess antiparasitic potential. From the in vitro analysis of the synthetic molecules, untreated trophozoites, and metronidazole at 100 μM, it was observed that three curcumin analogues (3a, 3e, and 5e) exhibited anti-T. vaginalis activity comparable to metronidazole (no significant statistical difference). Optimal antiparasitic concentrations were determined to be 80 μM and 90 μM for propanone derivatives 3a and 3e, respectively, and 200 μM for cyclohexanone derivative 5e. Kinetic growth curves showed that, after 24 h, the trophozoites were completely inhibited. At the tested concentrations, natural curcumin did not significantly inhibit the growth of trophozoites, therefore demonstrating that the designed synthetic molecules not only have better chemical stability, but also higher anti-T. vaginalis potential. Cytotoxicity analysis, performed on VERO cells, demonstrated low, moderate and high cytotoxic effects for analogues 3e, 5e and 3a, respectively. This study suggests that these analogues possess chemical features of interest to be further explored as alternatives for the treatment of trichomoniasis.

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.

Symmetrical and unsymmetrical substituted 2,5-diarylidene cyclohexanones as anti-parasitic compounds

Symmetrical and unsymmetrical bis-aryl-α,β-unsaturated ketones were synthesized in moderate to excellent yield by treating cyclohexanone with various aldehydes. Dimethylammonium dimethylcarbamate (DIMCARB) was used as both catalyst and reaction medium for the synthesis of monoarylidenes cycloadduct intermediates, which was further used to produce diarylidene cyclohexanones. All the 34 compounds synthesized were evaluated for their anti-proliferative activity, particularly against promastigote of Leishmania amazonensis, epimastigoteand trypomastigoteof Trypanosoma cruzi. Eighteen compounds displayed anti-leishmanial activity against promastigotes of L. amazonensis with IC50 values ranging from 2.8 to 10 μM. In addition, two compounds exhibited significant antitrypanosomal activity against epimastigotes of T. cruzi with IC50 values of 5.2 ± 0.8 and 3.0 ± 0.0 μM, while five compounds exhibited activity from 15.0 ± 1.4 to 30.2 ± 1.8 μM against trypomastigote of T. cruzi. Moreover, all compounds were more selective against the parasites than the epithelial cells. The unsymmetrical compounds 16, 28, 30 and 33 can be considered as favorable anti-parasitic lead molecule having IC50 and EC50 values in the low-micromolar range, better than the reference drug benznidazole, and low cytotoxicity against Vero cells. The potent compounds were screened in silico against 17 enzymes of T. cruzi and best scoring were found against Dihydroorotate Dehydrogenase.