Current Organic Synthesis - Volume 11, Issue 6, 2014

The Barton-McCombie reaction (B-M reaction) is deoxygenation of aliphatic alcohols via thioacylation followed by a radical cleavage. Variations of the reactions may utilize different thioacyl fragments and hydrogen sources. In this review article, however, we have focused on the applications of this reaction as a mild and functional group tolerant method in deoxygenation step in total syntheses of some well recognized natural products.

Imidazoles are a fascinating group of heterocyclic molecules with varying biological properties. Additionally, they form the nucleus of several commercial drugs. In this review, we describe the history of imidazoles from their discovery to their structural determination. We show that different synthetic methodologies are found in the literature. However, this review focuses on the evolution of the Radziszewski reaction used to synthesise tri- and tetra- substituted imidazoles, the different modifications of this reaction and the utilisation of new tools to construct these compounds. This review as a whole demonstrates the importance of a reaction that is over one century old and is still better than the newer alternatives.

Heterocycles constitute the largest diversity of organic molecules of chemical, biomedical, and industrial significance. They widely exist in numerous natural products, such as vitamins, hormones, antibiotics, alkaloids, herbicides, and dyes. They are also among the most frequently encountered scaffolds in numerous drugs and pharmaceutically relevant substances. This review highlights some remarkable achievements made recently in the application of multicomponent reactions (MCRs) to the design of pyrido- and pyrimidofused heterocycles by multi-component reactions that have appeared in the last ten years. MCRs reactions can dramatically reduce the generation of chemical wastes, costs of starting materials, and the use of energy as well as manpower. Moreover, the reaction period can be substantially shortened.

Many efforts have been made for developing novel and efficient methods to synthesize the glycosylated natural products. This review summed up recent advances on the synthesis of glycosylated natural products.

This present mini-review summarizes the recently published development and trends concerning catalysts based on immobilized complexes of transition metals which are designated for asymmetric Henry reaction. The paper presents examples of originally homogeneous catalysts which were anchored to organic carriers (such as dendrimers, polymers) or inorganic materials. The catalysts based on organic carriers are classified and discussed in accordance to their solubility in reaction medium. In the case of inorganic materials, the discussed catalysts were anchored to different types of surface of micro- and nano-particles. The discussion concerns the effect of immobilization of catalysts on the overall reaction yield, enantioselectivity, possible recycling, and the effect of recycling on the abovementioned parameters.

The pyrrolidine ring can be found in numerous natural products and in many pharmaceuticals. Hygrine, as an example of a pyrrolidine alkaloid, is the biosynthetic precursor of pharmacologically important tropane alkaloids. This review summarizes the synthetic routes toward racemic and enantiopure hygrine.

3,6-diphenyl-1,2,4,5-tetraoxane(DFT) has been prepared in order to study the effect of temperature on the reaction kinetics in methylcellosolve solution. The thermolysis reaction fulfills a kinetic law of the first order up to conversions approximately 60 % of the DFT. The values of ΔH#=20.2±1.0 kcal mol-1 and ΔS#= -25.3±1.4 cal mol-1 K-1 of the rupture of one O-O bond in the diperoxide molecule were obtained by measuring the remanent diperoxide at different reaction times by GC technique. Benzaldehyde and benzoic acid were detected by GC as the major organics products of the reaction.

Ketones were prepared by a modified Nef reaction using heterocyclic aryl nitroalkenes to react in a Fe-FeCl3-CH3COOH mixture with higher yield over 50% in sharp contrast with in Fe-HCl mixture with lower yield less than 30%, thus it’s cost-saving and relative environment friendly.

By an efficient biomimetic synthetic method, several novel 2-substituted benzimidazoles, benzoxazoles, and benzothiadazole were readily prepared in good yields under mild conditions with 2-substituted imidazolinium iodides as the tetrahydrofolate model compounds at the oxidation level of formate. The reaction is probably involved in a nucleophilic addition to the C=N bond at the imidazolinium ring, followed a 1,3-H migration at an imidazolidine intermediate and a salt elimination.

Novel bisquinoline derivatives of tetraazamacrocyclic compounds, namely 4,10-bis(7-chloroquinoline)-1,4,7,10-tetraazacyclododecane (1, Scheme 1); 4,10-bis(7-chloroquinoline)-1,7-dimethyl-1,4,7,10-tetraazacyclododecane (6, Scheme 2); 4,11-bis(7-chloroquinoline)- 1,4,8,11-tetraazabicyclo[6.6.2]hexadecane (6a, Scheme 3) and 4,10-bis(7-chloroquinoline)-1,4,7,10-tetraazabicyclo[5.5.2] tetradecane (6b, Scheme 3) which are potential antimalarial drugs have been synthesized. The macrocycle framework had to be modified to allow attachment of the substituent (4,7-dichloroquinoline) at the nitrogen atom. The initial synthesis of (1) by direct derivatization was inefficient for selective functionalization and consequently the desired product was isolated in low yield. We have found that by choosing N-methylpyrrolidinone as the reaction solvent, with triethylamine as base, and elevating the reaction temperature, product (1) was accessed with yields of up to 45%. Compounds 6, 6a and 6b were synthesized via regioselective modification of the macrocyclic framework before the attachment of the 4,7-dichloroquinoline substituent.

Studies were carried out to explore reactions of the enaminal, N,N-dimethylaminoacrolein (1c), with active methylene compounds. The results show that 1c reacts with 3-oxoalkanenitriles 2a and 2b to yield either the respective 2-(N,N-dialkylamino)pyridines 6a and 6b or pyridine-3-carbonitriles 7a and 7b depending on the reaction conditions. In addition, 1c reacts with malononitrile in ethanolic piperidine to produce N,N-dimethylamino- allylidenemalononitrile 9, whose structure was assigned by using X-ray crystallography. Coupling of 1c with p-chlorobenzenediazonium chloride in the presence of sodium acetate affords 2-(2-(4-chlorophenyl) - hydrazono) malonaldehyde 11, which is also generated by the reaction of 1,1,3,3-tetramethoxypropane with the same aryldiazonium salt. Also, a novel method to produce pyrazole-3-carboxaldehyde 13, involving reaction of 11 with chloroacetone in the presence of ethanolic triethylamine, was uncovered. Pyrazole-3-carboxaldehyde 13 was shown to be a precursor of 1,8-dioxo-octahydroxanthenes 15 and pyranopyrazole 17. Furthermore, 2-(2-(4-chlorophenyl)hydrazono)malonaldehyde 11 undergoes reactions with hydrazine hydrate and phenylhydrazine to give the respective arylazopyrazole derivatives 18a and 18b. Finally, the pyrimidone and thiopyrimidone derivatives 20a and 20b are formed by the reaction of 11 with urea and thiourea, respectively, in refluxing ethanol.