Letters in Organic Chemistry - Volume 13, Issue 6, 2016

A simple and efficient method has been developed for the synthesis of a new collection of isatin and 5-isatinylidenerhodanine derivatives carrying furan group, from N-(carboxymethyl)isatin through a multi-component reaction is explained. The reactive 1:1 intermediate formed from the reaction of isocyanides and dialkyl acetylenedicarboxylates was trapped at reflux temperature using N-(carboxymethyl)isatin derivatives to produce poly functionalized furan rings in good yields.

A simple and efficient synthesis of biscoumarin and dihydropyrano[c]chromene derivatives using catalytic amounts of imidazole or isoquinoline as organocatalyst under solvent-free conditions is reported. The present procedure offers advantages such as high to excellent yields, short reaction times, inexpensive operation, solvent-free conditions, reduced environmental consequences and simple workup.

In this study, a new, effective and environmentally benign procedure for the synthesis of dihydropyrimidinone and thione derivatives with various benzaldehydes, urea or thiourea, and ethyl acetoacetate in the presence of 1,4-diazabicyclo[2.2.2]octanium diacetate as a novel acidic ionic liquid, in high yield and short reaction time is reported. This method provides several advantages such as easy work-up, green, environmental friendliness and fast reaction condition along with high yields.

Background: In the field of asymmetric aminocatalysis, chiral catalysts derived from azoles (five-membered heterocycles containing exclusively N atoms) play an important role. Surprisingly, all the catalysts used for enamine and/or iminium ion activation derive from pyrrole or imidazole. We decided to test if other reduced azole derivatives could be used as organocatalysts and particularly in aminocatalysis via iminium ion activation. The azole derivatives that came naturally to mind are the 3,5-disubstituted 2-pyrazolines (also called 4,5-dihydro-1H-pyrazoles). Methods: We synthesized racemic 3,5-diphenyl-2-pyrazoline, separated both enantiomers by chiral-HPLC on a Lux-Cellulose-4 column (heptane/ethanol 70:30 as mobile phase), determined the absolute configuration of their hydrochloride salts (pyrazolinium) by the combined use of experimental rotatory power and B3LYP/6-311++G(d,p) theoretical calculations and use one the enantiomers, the R, as the catalyst. Results: We have demonstrated that the enantiopure (R)-3,5-diphenyl-2-pyrazoline is able to catalyze the Michael addition of 1-(4-nitrophenyl)propan-2-one to cinnamaldehyde and crotonaldehyde via iminium activation. Conclusion: This is the first example of activation of both types of enals, aliphatic and aromatic, via pyrazolinium salts and opens new possibilities to the design of other type of chiral organocatalysts than the traditional pyrrole and imidazole derivatives.

Background: Cyclic amino alcohols comprise one of the most important functional motifs of aminoglycoside-type antibiotics. Development of the strategies towards new cyclic amino alcohols allows a broader investigation of these compounds in biology and medicine. Much attention is paid to the preparation of aminoglycoside mimetics that have simpler structures, but retain the biological activity of parent structures. Oxirane ring opening is a synthetically significant reaction for the creation of new pharmaceutically important scaffolds. A distinguishing feature of this approach is the synthesis of amino alcohols with the assigned stereochemistry. Regio- and stereochemical diversity within a sugar-like moiety in those mimetics may subtly influence their biological activity. We propose a regio- and stereospecific route towards trisubstituted cycloheptanes. Methods: Initially, two diastereomeric 1,2-epoxy-3-(N-benzyl-N-methylamino)cycloheptanes with opposite orientation of the oxirane ring to the amino moiety were synthesized. Then, epoxide ring-opening reactions with different nucleophiles under acid- or base-catalyzed conditions were performed. The structure of the products was confirmed by two dimentional NMR methods. Results: Three types of regioisomers, according to the direction of the nucleophilic attack, were obtained. The regio- and stereoselective outcome of these reactions depends on the relative orientation of the oxirane ring and the nature of the catalyst. Conclusion: In summary, the regio- and stereospecific outcome of the epoxide ring cleavage of 1,2-epoxy-3- substituted cycloheptanes was highlighted. The route allows to synthesize new regio- and stereochemically diverse aminocycloheptanol derivatives on multi-gram scale, which could serve as prospective building blocks for the aminoglycoside antibiotic research. The benzyl removal and the further functionalization of nitrogen atom could provide the creation of novel scaffolds for the pharmaceutical and biotech research communities.

A number of thiophen-2(5H)-ones with different substituents in the 3-, 4- and 5-position have been synthesized and tested as inhibitors of biofilm production by the marine bacterium Vibrio harveyi BB120. Concentrations that inhibited 50% or 90% of biofilm formation (BIC50, BIC90) and of plantonic growth (PIC50, PIC90) are reported.

The reactive 1:1 intermediate obtained by the addition of triphenylphosphine to dialkyl acetylenedicarboxylates was trapped by 1,2-diketone monoximes to generate functionalized 1,2-oxazine derivatives through intramolecular Wittig reaction without any catalyst in excellent yields.

The cyclooctadepsipeptide PF1022A (1) and its semisynthetic, commercial analogue emodepside (2) have been established as excellent anthelmintics with resistance breaking properties. For a second generation anthelmintic cyclooctadepsipeptide with improved activity for instance against human worm infections new derivatives are required. We detail here for the first time the synthesis of phenylheteroaromatic analogues of PF1022A prepared by efficient click-reactions.

Background: The commercially available dimeric cinchona alkaloids based on C-9 ether bond connecting are limited by the absence of Brønsted acid moiety and cannot meet the enantioselectivity demand. Objective: In this study, a family of novel C2-symmetric bis-cinchona alkaloid derivatives possessing a range of mono- and bidentate hydrogen bond donor groups at the C-9 is now reported. Method: These novel C2-symmetric bis-cinchona alkaloid derivatives were synthesized by a facile route. Results: These novel C2-symmetric bis-cinchona alkaloid derivatives exhibit a rare example of Brønsted acid moiety of C-9, basic tertiary amine moiety, and a rigid enzyme-like pocket, suggesting their potential, broadly useful bifunctional organic catalysts for asymmetric synthesis.

An efficient process for the large-scale synthesis of 4-methylnicotinic acid is developed. The synthetic route utilized 2,6-dichloro-4-methylnicotinonitrile as the starting material, which was commercially available. The key step in the sequence was the reductive dechlorination in the presence of zinc and ammonia to provide an intermediate which was hydrolyzed to the described acid. The reaction parameters optimization and improvement of purification are also presented. This approach, suitable for batch processing, is of interest basically to research laboratories and also to suppliers in the research and fine chemicals market.

A facile, efficient, green, and environmentally benign method is described for the synthesis of 2,3-dihydroquinazolin-4(1H)-ones by direct cyclocondensation of 2-aminobenzamide with aldehydes or ketones in water using PEG-SO3H as an acidic catalyst under room temperature. This new method totally avoids the use of organic acids, toxic or expensive solvents and affording the corresponding product in good to excellent yields in this reaction.

We easily prepared the well characterized ruthenium nanoparticles intercalated montmorillonite clay catalyst to catalyze amine mediated CO2 hydrogenation to formic acid. Ru exchanged MMT clay was reduced under hydrogen atmosphere in PEG (400) solvent system to achieve the Ru metal nanoparticles with average 25.5±2 nm size within the interlayer spacing of MMT clay. 17 different cyclic and acyclic amines were studied for CO2 loading and further tested as the solvent system with ethanol for CO2 hydrogenation reaction. The corresponding hydrogenated product (formic acid) was obtained in high TON /TOF value with 40% ethanolic solution of tetraethylenepentamine. Six times catalyst recycling is the added advantage of this proposed reaction protocol.