Letters in Organic Chemistry - Volume 8, Issue 9, 2011

A simple and high yield route to 3,4,5-trisubstituted 1,4-dihydropyridine systems via an interesting intermolecular condensation and double decarboxylation is described.

A simple and efficient Michael addit ion of isatin to acrylate in the presence of KOH was described. Methyl β-(2,3-dioxoindolin-1-yl) propanoate was synthesized firstly by the addition of isatin to methyl acrylate in a feasible approach using 10% KOH as catalyst in DMF with the highest yield of 72.5% under the optimized conditions. A series of β-(2,3-dioxoindolin-1-yl) propanoate derivatives was synthesized according to this approach and gave moderate to relative high yields. The directive distinct color changes in this reaction were illuminated by the reaction mechanism analysis.

A mild, efficient and highly convenient protocol is reported for the synthesis of a series of polyphenolic amides using ferric exchanged montmorillonite as a strong solid acid catalyst. This heterogeneous catalyst has an advantage of a strikingly simple work up procedure over conventional homogeneous acids. The catalyst is recoverable and recyclable.

The solid-phase synthesis of di-N-acetyl-β-chitobiosyl allosamizoline 2 was reported. After the 6-O-benzyl allosamizoline 16, NHCbz trichloroacetimidate donors 7, and 14 were synthesized; solid-phase synthesis was performed using the Wang resin as support. The target di-N-acetyl-β-chitobiosyl allosamizoline 2 was obtained by iterative glycosylation reactions, catalytic hydrogenation, acetylation, and deacetylation, respectively.

A simple and practical method to prepare ‘libraries’ of substituted 1-phenylpiperazine building blocks in parallel format has been developed.

A series of mono- and bis-pyrimido-[1,2-a]benzimidazole derivatives is synthesized by the regioselective multicomponent condensation reaction of aldehyde and malononitrile with 2-aminobenzimidazole in the presence of alum as a recyclable and efficient catalyst for this condensation.

A series of novel 6-fluoro1,4-dihydro-4-oxo-3-quinoline carboxylic acid dimers (34-37), were synthesized as potential antibacterial agents from commercially available fluoro benzoic acids.

7-benzyl-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4(3H)-ones were synthesized by base catalytic reactions of nucleophilic reagents (aliphatic amines, alcohols or phenols) with carbodiimides 4, which were obtained from the aza-Wittig reaction of iminophosphoranes 3 with aromatic isocyanates.

A new fluorescent sensor 1 was designed and synthesized through the condensation of indole-3-aldehyde and N-(2-hydroxyethyl)ethylenediamine. It exhibits good sensitivity and selectivity for the copper cation over other cations such as K+, Na+, Ca2+, Cr2+, Mg2+, Zn2+, Al3+ and Fe3+. The fluorescence intensity of the sensor was decreased with increasing the concentration of Cu2+. The analysis of the Benesi-Hildebrand equation indicated the formation 1:1 complex of 1 and Cu2+ with association constant Kass=3.34×105M.

New 1,5-dicarbonyl compounds were prepared, as versatile precursors to pyridine derivatives, by a tandem Claisen-Schmidt condensation/ Michael addition reaction, that is condensation between 5-chloro-3-methyl-1-phenyl-1Hpyrazole- 4-carbaldehyde and acetophenones, and the formed adduct then reacts with a second molecule of acetophenone. The preparation of substituted pyridines was achieved using NH4OAc as nitrogen source under solvent-free microwave irradiation.

Using 5% aq. NaOH, a simple method for the transformation of 3-cyanoacetylindoles 2(a-e) into 3- acetylindoles 3 (a-e), in good yields, is reported. Tetrabutylammoniumbromide (TBAB) is found to be an efficient phase transfer catalyst for the synthesis of N-alkyl derivatives 5(a-t) of 3-acetylindoles 3(a-e) giving products in excellent yields. 2 (a-e) were themselves obtained from simple indoles 1 (a-e) by reaction with cyano acetic acid in the presence of propionic anhydride at 100 °C for 5-10 min. Partial hydrolysis of 2 (a-e) under hot acidic conditions yielded the corresponding carboxamides α-(3-indolecarboxoyl)acetamides 4(a-e). Which could be readily transformed into the respective 3(a-e) by refluxing with 5% aq. NaOH for 2-2.5 h.

Various pyrimidine derivatives (1a-c) were synthesized using the Biginelli three component cyclocondensation reactions of a β-diketone, arylaldehyde, and thiourea, under microwave irradiation and conventional conditions. The acetylation of compound 1a gave 3-acetyl thioxopyrimidin 2. Also, thiazolopyrimidine (3) and (4) derivatives were obtained by a simple one-pot condensation reaction of starting compounds 1a, and 1b with 2-bromopropionic acid. The prepared compounds were screened for their antimicrobial activities against Gram-positive, Gram-negative bacteria and fungi using micro dilution procedure. The results of the study showed that the compound 4 was effective and selective for antimicrobial activity against the tested bacteria and fungi. Thus, we suggested that the compound 4 might be a new potential antimicrobial substance for bacteria and fungi.

Synthesis of Sildenafil by the O-alkylation of 5-[2-hydroxy-5-(4-methylpiperazin-1-ylsulphonyl)phenyl]-1- methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo-[4,3-d]pyrimidin-7-one 8 proved difficult because concomitant alkylation of the pyrimidine moity also occurred. The selective O-alkylation was carried by DCC assisted decarboxilative etherification of the carbonate 9.

Commercially available titanocene dichloride was firstly used as an extremely efficient catalyst for a three component one-pot reaction of an amine, an aldehyde (ketone), and a dialkyl phosphite to form α-aminophosphonates under solvent-free conditions at ambient temperature in good to high yields, providing a green, rapid and convenient method for the synthesis of α-aminophosphonates.

Epimeric 20S, 24-epoxy-dammarane-3β, 6α, 12β, 25-tetraol acetic ester was synthesized from 20(S)- protopanaxatriol in the presence of acetic anhydride and the product oxidated by m-CPBA. 20S, 24R-epoxy dammarane- 3β, 6α, 12β, 25-tetraol (ocotillol derivative) and its epimer were synthesized by saponification in the presence of sodium hydroxide in 1:1 molar ratio. The structures of the two compounds were characterized by X-ray diffraction method. The results showed the configuration of C-24 of two epimers as S-form (4, ocotillol derivative) and R-form (3, epimer), respectively.