1125-99-1Relevant academic research and scientific papers
Enamine Organocatalysts for the Thiol-Michael Addition Reaction and Cross-Linking Polymerizations
Sinha, Jasmine,Soars, Shafer,Bowman, Christopher N.
, p. 1693 - 1701 (2021)
This article describes an efficient enamine organocatalyzed thiol-Michael click reaction and its broad application in cross-linking polymerizations. A series of enamines was shown to catalyze the thiol-Michael reaction via a nucleophilic pathway. By varying the amines as well as the ring size of the ketones, enamines were designed with broad ranges of nucleophilic character ranging from 11 to 17 on the Mayr nucleophilicity scale. Upon evaluating the enamines' organocatalytic effect on the kinetics of reactions involving a thiol and Michael acceptor, wherein butyl 3-mercaptopropionate and 1-hexyl acrylate were used as model reactants, enamines were shown to outperform their base analogs. The efficiency and overall reaction yields, ranging from 11 to 92% based on the thiol conversion, were highly dependent upon the nucleophilicity of the enamines employed. Interestingly, in situ formation of an enamine via photo-deprotection of an amine in the presence of cyclic ketones facilitated the thiol-Michael reaction efficiently while simultaneously enabling higher functional group conversion. This efficiency in the reaction kinetics and conversion was extended to multifunctional derivatives, which resulted in the formation of highly cross-linked polymers.
Domino Synthesis of Benzo-Fused β,γ-Unsaturated Ketones from Alkenylboronic Acids and N-Tosylhydrazone-Tethered Benzonitriles
Plaza, Manuel,Paraja, Miguel,Florentino, Lucía,Valdés, Carlos
, p. 632 - 635 (2019)
The transition-metal-free domino reaction between alkenylboronic acids and N-tosylhydrazones from o-(2-oxoalkyl)- and o-(3-oxoalkyl)benzonitriles leads to β, γ-unsaturated indanones and tetralones featuring an α-"all-carbon" quaternary center. The employment of derivatives of α-substituted cyclopentanones and cyclohexanones led to the stereoselective preparation of β, γ-unsaturated tetrahydrocyclopenta[a]inden-8(1H)-ones, hexahydrofluorenones, and hexahydroanthracenones as cis-fused single stereoisomers. A domino sequence involving diazo compound formation/reductive alkenylation/1,3-borotropic rearrangement/intramolecular bora-aza-ene reaction is proposed to justify the formation of the products as well as the stereoselectivity.
Microwave-Assisted Facile Synthesis of Imines and Enamines using Envirocat EPZGR as a Catalyst
Varma, Rajender S.,Dahiya, Rajender
, p. 1245 - 1246 (1997)
In a simple microwave-assisted and environmentally benign approach, aldehydes and ketones react readily with primary and secondary amines to afford imines and enamines, respectively, under solvent-free conditions using Envirocat EPZGR as a catalyst.
Rate constants for 1,2-hydrogen migration in cyclohexylidene and in substituted cyclohexylidenes
Pezacki, John Paul,Couture, Philippe,Dunn, James A.,Warkentin, John,Wood, Paul D.,Lusztyk, Janusz,Ford, Francis,Platz, Matthew S.
, p. 4456 - 4464 (1999)
Laser flash photolysis (UV-LFP, 308 nm) of suitably substituted oxadiazolines leads to cyclohexylidene (14a), 4-tert-butyl-cyclohexylidene (14b), 2-trifluoromethylcyclohexylidene (14d), 8-aza-8-methyl[3.2.1]oct-3- ylidene (14e), diethylcarbene (14f), and ethyl(methyl)carbene (14h). Carbene intermediates were inferred from the products of steady state photolyses, and their pyridinium ylides were inferred from transient absorption spectra observed when pyridine was present. Yields of the pyridinium ylides 15a-h as a function of pyridine concentration gave the lifetimes (τ) for carbenes 14a-h in cyclohexane, cyclohexane-d12, and benzene solutions, at 22 °C. The intermediacy of cyclohexylidene (14a) was inferred from the observation of cyclohexene formed in both the LFP and steady state (SS) experiments. The major products from dual wavelength irradiation of the oxadiazolines (at 254 and 300 nm) were those of 1,2-migration of hydrogen (1,2-H) in the corresponding carbenes. 2-Trifluoromethylcyclohexylidene gave 3- trifluoromethylcyclohexene and 1-trifluoromethylcyclohexene in a 9.8:1 ratio. The kinetic data support the conclusion that 1,2-H in the cyclohexylidenes is accelerated, relative to 1,2-H in dimethylcarbene. A 4-tert-butyl substituent has a negligible effect on the rate constant for 1,2-H, but the CF3 group at the α-position decelerates 1,2-H by roughly 10-fold, as inferred from the distribution of products.
1 microwave-induced montmorillonite-mediated facile synthesis of enamines
Yadav, Ram Naresh,Banik, Indrani,Srivastava, Ashok Kumar,Ramos, Katherine,Banik, Bimal Krishna
, p. 249 - 254 (2020)
Montmorillonite clay-mediated simple and high yielding protocol for the synthesis of various enamines with secondary amines and ketones is developed under microwave condition. This protocol is very convenient to accesses the enamines from cyclic amines with various carbonyl compounds in high yield under mild reaction conditions with short reaction time.
Nitric oxide inhibitory activity and antioxidant evaluations of 2-benzoyl-6-benzylidenecyclohexanone analogs, a novel series of curcuminoid and diarylpentanoid derivatives
Leong, Sze Wei,Mohd Faudzi, Siti Munirah,Abas, Faridah,Mohd Aluwi, Mohd Fadhlizil Fasihi,Rullah, Kamal,Lam, Kok Wai,Abdul Bahari, Mohd Nazri,Ahmad, Syahida,Tham, Chau Ling,Shaari, Khozirah,Lajis, Nordin H.
, p. 3330 - 3337 (2015)
Abstract A series of twenty-four 2-benzoyl-6-benzylidenecyclohexanone analogs were synthesized and evaluated for their nitric oxide inhibition and antioxidant activity. Six compounds (3, 8, 10, 17, 18 and 19) were found to exhibit significant NO inhibitory activity in LPS/IFN-induced RAW 264.7 macrophages, of which compound 10 demonstrated the highest activity with the IC50 value of 4.2 ± 0.2 μM. Furthermore, two compounds (10 and 17) displayed antioxidant activity upon both the DPPH scavenging and FRAP analyses. However, none of the 2-benzoyl-6-benzylidenecyclohexanone analogs significantly scavenged NO radical. Structure-activity comparison suggested that 3,4-dihydroxylphenyl ring is crucial for bioactivities of the 2-benzoyl-6-benzylidenecyclohexanone analogs. The results from this study and the reports from previous studies indicated that compound 10 could be a candidate for further investigation on its potential as a new anti-inflammatory agent.
Synthesis and biological evaluation of asymmetrical diarylpentanoids as antiinflammatory, anti-α-glucosidase, and antioxidant agents
Leong, Sze Wei,Awin, Tahani,Mohd Faudzi, Siti Munirah,Maulidiani,Shaari, Khozirah,Abas, Faridah
, p. 2002 - 2009 (2019)
A series of seven new (1, 3, 6, 7, 10, 12, and 13) and six (2, 4, 5, 8, 9, and 11) known diarylpentanoid analogs were synthesized and assessed for their nitric oxide (NO) and α-glucosidase inhibitory activities as well as their antioxidant capacity. Nine compounds (2, 3, 4, 5, 6, 8, 11, 12, and 13) were found to exhibit comparable activity to that of curcumin (IC50= 13.0 μM), in which compound 8 has displayed strongest NO inhibitory activity with the IC50 values of 17.5 μM. Meanwhile, four compounds (1, 7, 12, and 13) were found to possess better α-glucosidase inhibitory activity than that of curcumin (30.9 μM), with the IC50 values ranging from 19.4 to 24.9 μM. On the other hand, none of the synthesized compounds has achieved better DPPH scavenging activities than that of curcumin, indicating the relatively poor antioxidant potential of desired diarylpentanoid structure. Structure-activity relationship (SAR) study disclosed that the existence of meta-hydroxyphenyl and bromo groups is crucial for antiinflammatory and anti-α-glucosidase activities, respectively. Molecular docking study showed that bromo moiety could form additional hydrophobic contacts with α-glucosidase, thereby increased the inhibition of diarylpentanoid against α-glucosidase. The overall results suggested that diarylpentanoids with poly-meta-hydroxylated phenyl ring and multiple bromo groups may lead to the discovery of new diarylpentanoids with both antiinflammatory and anti-α-glucosidase activities.
Preparation of Hexahydrocarbazole Derivatives by Reductive Indolization
Christoffers, Jens,Dierks, Anna,Fliegel, Lukas,Schmidtmann, Marc
, p. 7164 - 7175 (2020)
The reductive indolization is a two-step protocol performed in one flask: First, the acid-mediated Fischer indolization of a cyclic ketone with phenylhydrazine forms an iminium ion which is subsequently reduced by a hydrido borate reagent to the indoline as the final product. We utilized this new strategy for the preparation of hexahydrocarbazole derivatives with a side chain in the quaternary C4a-position. Starting materials were several N1- and aryl-substituted phenylhydrazines and a cyclic ketone with propanoic ester moiety, which is the product of the conjugated addition of cyclohexanone to ethyl acrylate. Furthermore, benzannulated congeners as well as a pyrido[4,3-b]indole derivative were accessed. The hexahydrocarbazole defines a molecular scaffold with two points of diversification. Therefore, several derivatives at N9 and at the C4a-side chain were prepared.
Are oxazolidinones really unproductive, parasitic species in proline catalysis? - Thoughts and experiments pointing to an alternative view
Seebach, Dieter,Beck, Albert K.,Badine, D. Michael,Limbach, Michael,Eschenmoser, Albert,Treasurywala, Adi M.,Hobi, Reinhard,Prikoszovich, Walter,Linder, Bernard
, p. 425 - 471 (2007)
The N,O-acetal and N,O-ketal derivatives (oxazolidinones) formed from proline, and aldehydes or ketones are well-known today, and they are detectable in reaction mixtures involving proline catalysis, where they have been considered 'parasitic dead ends'. We disclose results of experiments performed in the early 1970's, and we describe more recent findings about the isolation, characterization, and reactions of the oxazolidinone derived from proline and cyclohexanone. This oxazolidinone reacts (THF, room temperature) with the electrophiles β-nitrostyrene and chloral (=trichloroacetaldehyde), to give the Michael and aldol adduct, respectively, after aqueous workup (Scheme 5). The reactions occur even at -75° when catalyzed with bases such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) or EtN(i-Pr)2 (DIPEA) (10%; Table 1). It is shown by NMR (Figs. 1 and 3) and IR analysis (Figs. 2 and 4) that the primarily detectable product (before hydrolysis) of the reaction with the nitro-olefin is again an oxazolidinone. When dissolved in hydroxylic solvents such as MeOH, 'hexafluoroisopropanol' ((CF3) 2CHOH; HFIP), AcOH, CF3COOH, or in LiBr-saturated THF, the ring of the oxazolidinone from cyclohexanone and proline opens up to the corresponding iminium ion (Tables 2-4), and when treated with strong bases such as DBU (in (D8)THF) the enamino-carboxylate derived from proline and cyclohexanone is formed (Scheme 8). Thus, the two hitherto putative participants (iminium ion and enamine) of the catalytic cycle (Scheme 9) have been characterized for the first time. The commonly accepted mechanism of the stereoselective C,C- or C,X-bond-forming step (i.e., A-D) of this cycle is discussed and challenged by thoughts about an alternative model with a pivotal role of oxazolidinones in the regio- and diastereoselective formation of the intermediate enamino acid (by elimination) and in the subsequent reaction with an electrophile (by trans-addition with lactonization; Schemes 11-14). The stereochemical bias between endo- and exo-space of the bicyclo[3.3.0]octane-type oxazolidinone structure (Figs. 5 and 6) is considered to possibly be decisive for the stereochemical course of events. Finally, the remarkable consistency, with which the diastereotopic Re-face of the double bond of pyrrolidino-enamines (derived from proline) is attacked by electrophiles (Schemes 1 and 15), and the likewise consistent reversal to the Si-face with bulky (Aryl) 2C-substituents on the pyrrolidine ring (Scheme 16) are discussed by invoking stereoelectronic assistance from the lone pair of pyramidalized enamine N-atoms.
Chemoenzymatic route to optically active dihydroxy cyclopenta[b]naphthalenones; precursors for decalin-based bioactive natural products
?zdemirhan, Devrim,Sar??elik, ?zlem
, p. 118 - 124 (2017)
The development of an efficient chemoenzymatic route for the synthesis of optically active dihydroxy cyclopenta[b]naphthalenones; (+)-1,4a-dihydroxy-4a,5,6,7,8,8a,9,9a-octahydro-1H-cyclopenta[b]naphthalen-2(4H)-one (+)-10 and (+)-1,8a-dihydroxy-4a,5,6,7,8,8a,9,9a-octahydro-1H-cyclopenta[b]naphthalen-2(4H)-one (+)-11 is described. Different lipases and esterases were tested in the enzymatic hydrolysis of the corresponding acetates (±)-4a-hydroxy-2-oxo-2,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-cyclopenta[b]naphthalen-1-yl acetate (±)-8, (±)-8a-hydroxy-2-oxo-2,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-cyclopenta[b]naphthalen-1-yl acetate (±)-9, CRL (Candida Rugosa Lipase) and PLE (Pig Liver Esterase) were found to be the most effectual enzymes; for (?)-8 by 47% ee with the corresponding dihydroxy; (+)-10 by 98% ee in the presence of CRL; whereas, (?)-8 was obtained with 40% ee with the corresponding dihydroxy, (+)-10 with 58% ee in the PLE hydrolysis. It was concluded that CRL was the best biocatalyst for the substrate (±)-8. Moreover, enzymatic resolution in the presence of CRL yields, (?)-9 with 46% ee with the corresponding dihydroxy derivative; (+)-11 with 98% ee; however, in the presence of PLE, yields (?)-9 with 36% ee as well as the related dihydroxy derivative; (+)-11 with 49% ee respectively. The study concluded that CRL is the best biocatalyst for compounds (±)-8 and (±)-9.
