Recent advancement and novel application of organocatalyzed aldol condensation reactions: A comprehensive review

Background: Aldol reactions play an important role in the development of organic synthesis-owing to their critical importance for the forming of carbon-carbon bonds while concurrently one or two chiral centers come into being. In the modern scenario, the Aldol condensation reaction has arisen as perhaps the most significant reaction for the formation of novel medicinal agents exhibits promising pharmacological activities. Objective: The purpose of this study is to present newer synthetic approaches through Aldol condensation reaction for the synthesis of diverse scaffolds to explore the promising various types of biological activities. Methods: Aldol condensation concerns the nucleophilic addition reaction of a ketone enolate to an aldehyde to form aldol or β- hydroxy ketone. Occasionally, the aldol addition product losing water molecule yields an α, β-unsaturated ketone. Results: Results showed that amino acids and all lengths of peptides are utilized as chiral catalysts. As of now, the arrangement of catalysts that have been accounted for is intensely one-sided towards proline. This is to some degree because of its exceptional status among the normally happening amino acids as an auxiliary amine and to its restricted underlying adaptability. Conclusion: The present study thus provides useful insight concerning the promising coherent way for the synthesis of prolinamide analogue of proline, through a direct asymmetric aldol condensation reaction. Thus, the current study summarizes various Aldol condensation reactions for the synthesis of novel agents as well as their promising pharmacological importance.

Catalytic Synthesis of Methacrolein via the Condensation of Formaldehyde and Propionaldehyde with L-Proline Intercalated Layered Double Hydroxides

Aldol condensation reactions are very important C–C coupling reactions in organic chemistry. In this study, the catalytic performance of layered double hydroxides (LDHs) in the aldol condensation reaction of formaldehyde (FA) and propionaldehyde (PA) was investigated. The MxAl-LDHs (denoted as re-MxAl–LDHs; M = Ca and Mg; X = 2–4), as heterogeneous basic catalysts toward the aldol condensation reaction, were prepared via a two-step procedure. The catalyst exhibited a high PA conversion (82.59%), but the methacrolein (MAL) selectivity was only 36.01% due to the limitation of the alkali-catalyzed mechanism. On this basis, the direct intercalation of L-proline into LDHs also has been investigated. The influences of several operating conditions, including the temperature, reaction time, and substrate content, on the reaction results were systematically studied, and the optimized reaction conditions were obtained. The optimized Mg3Al–Pro-LDHs catalyst exhibited a much higher MAL selectivity than those of re-MgxAl–LDHs.

Influence of aldol condensation processes on the formation of surface films during friction in ester lubricants

The boundary lubrication mode is usually implemented in conditions of low sliding speeds and high loads. The formation of strong boundary lubricating films under this friction mode determines the operability and durability of the friction units. It is believed that the formation of surface boundary films during friction includes the stages of the lubricant oxidation, and the aldol condensation reaction of oxidized molecules. As a result, high-molecular substances called “friction polymers” are formed. The paper studies the formation of surface films in the presence of substances with different reactivity in the aldol condensation and Claisen condensation reactions. Sunflower oil, bis (2-ethylhexyl) sebacate (DEHS), triisodecyl benzene-1,2,4-tricarboxylate (TC) were used as lubricants. It is shown by ATR IR-spectroscopy of that the common thing for the studied oils is that the C=O and C-O groups participate in the formation of boundary films in these oils. The addition of substances, active in aldol condensation reactions, into lubricants does not accelerate the formation of boundary films. Additives that can chemically interact with iron contribute to the dissolution of the surface oxide film and accelerate the formation of boundary layers. The formation of “friction polymers” occurs when the lubricant molecules interact with the metal surface.

Functionalization of Betulinic Acid with Polyphenolic Fragments for the Development of New Amphiphilic Antioxidants

The present work aimed at the valorization of biomass derived compounds by their transformation into new added-value compounds with enhanced antioxidant properties. In this context, betulinic acid (BA) was decorated with polyphenolic fragments, and polyhydroxylated (E)-2-benzylidene-19,28-epoxyoleanane-3,28-diones 4a–d were obtained. For that, the synthetic strategy relied on base-promoted aldol condensation reactions of methyl betulonate, which was previously prepared from natural BA, with appropriate benzaldehydes, followed by cleavage of the methyl protecting groups with BBr3. It is noteworthy that the HBr release during the work-up of the cleavage reactions led to the rearrangement of the lupane-type skeleton of the expected betulonic acid derivatives into oleanane-type compounds 4a–d. The synthesized compounds 4a–d were designed to have specific substitution patterns at C-2 of the triterpene scaffold, allowing the establishment of a structure-activity relationship. The radical scavenging ability of 4a–d was evaluated using the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid radical cation (ABTS•+) scavenging assays. In particular, derivative 4c, bearing a catechol unit, revealed to be the most efficient scavenger against both free radicals DPPH• and ABTS•+. Subsequently, we designed two analogues of the hit derivative 4c in order to achieve more potent antioxidant agents: (i) the first analogue carries an additional unsaturation in its lateral chain at C-2 (analogue 5) and (ii) in the second analogue, E-ring was kept in its open form (analogue 6). It was observed that the presence of an extended π-conjugated system at C-2 contributed to an increased scavenging effect, since analogue 5 was more active than 6, α-tocopherol, and 4c in the ABTS•+ assay.

A simple and easy to perform synthetic route to functionalized thienyl bicyclo[3.2.1]octadienes

In order to prepare novel polycyclic derivatives of bicyclo[3.2.1]octadiene systems fused with a thiophene ring, photochemical cyclization and aldol condensation reactions were carried out. The starting substrates were easily obtained by a Vilsmeier–Haack reaction of bicyclo[3.2.1]octadiene thiophene derivatives with dimethylformamide. From the obtained carbaldehydes, novel methyl, methoxy, and cyano-substituted styryl thienobenzobicyclo[3.2.1]octadiene derivatives were synthesized through Wittig reactions and subjected to photochemical cyclization, in terms of obtaining the new annulated structures. As part of this study, the aldol reaction of the starting 2-substituted carbaldehyde with acetone was also performed, which produced the thieno-fused benzobicyclo[3.2.1]octadiene compound with an extended conjugation.

Antioxidant properties of certain C5 substituted 4-arylimino-thiazolidin-2-ones

Aim. Expanding the synthetic potential of 4-arylimino-thiazolidin-2-ones; a study of reactivity; and primary screening for antioxidant activity of synthesized compounds. Materials and Methods. All chemicals were of analytical grade and commercially available. When performing the synthetic part of the work, reagents manufactured by Merck (Germany) and Sigma-Aldrich (USA) were used. All the reagents and solvents were used without further purification and drying. Methods of organic synthesis, physical and physical-chemical methods of analysis of organic compounds (NMR spectroscopy, elemental analysis) were used in the study. Results and Discussions. The peculiar pharmacological activities of 4-iminothiazolidin-2-ones prompted us to synthesize certain С5 substituted 4-arylimino-thiazolidin-2-ones and test them for antioxidant activity. The specified scaffold represents a convenient intermediate in order to afford С5 substituteds 4-arylimino-thiazolidin-2-ones. The active methylene group presence in C5 position of the basic scaffold provides an entry for its utilization in azo coupling and aldol condensation reactions leading to appropriate 5-aryl-hydrazono and 5-arylidene derivatives of 4-arylimino-thiazolidin-2-one generation. The structures of the obtained compounds were confirmed by 1H NMR spectroscopy and elemental analysis. The spectroscopic data of all compounds correspond to the proposed structures. The antioxidant activity of the synthesized compounds was measured in vitro by the method of scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. DPPH radical found many applications due to its high stability in a methanolic solution and intense purple color. In its oxidized form, the DPPH radical has an absorbance maximum at a wavelength of 517 nm. For the first time, antioxidant activity was identified among С5 substituted 4-arylimino-thiazolidin-2-ones. Conclusions. Based on azo coupling and aldol condensation reactions, structural modification of the C5 position of certain 4-arylimino-thiazolidin-2-ones was conducted. For all synthesized compounds, primary pharmacological screening for antioxidant activity was performed. Three highly active compounds with a pronounced antioxidant effect have been identified, which approach or exceed ascorbic acid in terms of activity. Key words: organic synthesis, 4-arylimino-thiazolidin-2-ones, 2,2-diphenyl-1-picrylhydrazyl, antioxidant activity