Letters in Organic Chemistry - Volume 10, Issue 3, 2013

The synthesis of enantiomers of 6-tert-butyl-6-methylmorpholine-2,5-dione (3) using Wang resin supported 2- chloro- or 2-bromo- pyridinium triflate is described. The applied methodology could be considered as an interesting alternative to “classical” one and enables the synthesis of 6-tert-butyl-6-methylmorpholine-2,5-dione with higher yields and the isolation of product (3) is significantly easier.

A cost-effective synthetic approach to prepare vildagliptin under gentle experimental conditions has been reported with good yield and high purity. It was initiated with L-proline via successful reaction with chloroacetyl chloride in THF (Tetrahydrofuran) to give the 1-(2-chloroacetyl)-pyrrolidine-2-carboxylic acid, which was then treated by TCT (2, 4, 6-trichloro-1, 3, 5-triazine) in DCM (dichloromethane), and converted into 1-(2-chloroacetyl)-pyrrolidine-2-carboxamide, then further converted into 1-(2-chloroacetyl)-pyrrolidine-2-carbonitrile after dehydrated by TCT in DMF (N, N- dimethylformamide), the latter product was reacted with 3-aminoadamantanol to get vildagliptin. The total yield of vildagliptin was about 48%, the purity was about 99%.

A green and efficient method for synthesis of α,α´ -bis (arylidene) cycloalkanones, starting from aromatic aldehydes in reaction with ketones using sulfonated polyethylene glycol 6000 (PEG-SO3H) as a stable, reusable and biodegradable catalyst under solvent-free conditions at 80 °C is described. The use of a nontoxic, inexpensive, easily available and recyclable catalyst makes this protocol practical, environmentally friendly and economically attractive.

La(NO3)3.6H2O was used as an efficient catalyst for highly diastereoselective synthesis of functionalized piperidines by one-pot five-component reactions of anilines and aromatic aldehydes with acetoacetic esters. This strategy proceeds by way of the Knoevenagel reaction followed by inter-molecular aza-Diels-Alder reaction. The main features of the current method comprise mild reaction conditions, easy work-up, eco-friendliness, high atom economy, short times and the products were isolated with high yields.

A novel route for the synthesis of tetrahydroimidazo [1,2-a] pyrimidine-6-carboxylate derivatives in presence of 1-ethyl-3-methyl imidazolium hydrogen sulphate ionic liquid at room temperature has been reported via Biginelli reaction. The process offer several advantages such as short reaction time, excellent yield of products, simple work up procedure etc. 1-ethyl-3-methyl imidazolium hydrogen sulphate ionic liquid is utilized as solvent system and catalyst to enhance the rate of reactions.

New 14-(Aryl)-14H-naphto[2,1-b]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-acetonitriles have been prepared. The chemical behaviour of these compounds was studied towards Knoevenagel condensation with salicylaldelyde derivatives, thus, a series of 2-(coumarin-3’’-yl)-14(Aryl)-14H-naphto[2,1-b]pyrano[3,2-e][1,2,4]triazolo[1,5- c]pyrimidines was obtain-ed. Their structures were characterized with IR, ES-HR-MS, 1H NMR and 13C NMR.

L-proline catalyzed one-pot three-component condensation reaction of aromatic aldehydes, malononitrile and naphthols proceeded in EtOH to afford corresponding 2-amino-4H-chromenes in high to excellent yields at reflux conditions. The protocol found to be fairly general and the catalyst was reused in subsequent reactions with consistent activity. Moreover, this method offers several advantages including high to excellent yields of products as well as a simple experimental, work-up procedure and product separation without further purification with column chromatography which makes it a useful and attractive process for the synthesis of these compounds.

1,4,7,10-Tetraazacyclododecane was synthesized through 4 steps by using easily available diphenylsulfonium triflate as a key annulation reagent. The reaction condition was very mild and the yield was high. After oxidation and hydrolysis, 1,4,7,10-Tetraazacyclododecane, which had been proven to be the pivotal precursor for a wide range of MRI contrast reagents, was produced in an overall yield of 31%.

3,4,5-substituted furan-2(5H)-ones were One-Pot Multi-Component synthesized by the reaction of aldehydes, amines and dialkyl acetylenedicarboxylates using silica gel-supported polyphosphoric acid (PPA/SiO2) at room temperature. This reaction provides a convenient and efficient synthetic method of furan-2(5H)-one derivatives, and also reusability of catalyst.

In this research project, a combination of poly(N,N'-dibromo-N-ethylene-benzene-1,3-disulfonamide) [PBBS] and/or(N,N,N',N'-tetrabromobenzene-1,3-disulfonamide) [TBBDA] with sodium nitrite in the presence of wet SiO2 (50% w/w) was used as an efficient nitrosating agent for the conversion of secondary amines to their corresponding nitroso compounds. N-Nitrosation reaction has been performed in dichloromethane at room temperature under mild and heterogeneous conditions. The reaction is operationally simple and corresponding products were achieved in good to excellent yields.

N-Formylation of amines has efficiently been carried out in excellent yields by treatment of amines with triethyl orthoformate in water under ultrasound irradiation. The process is remarkably simple and environmentally benign.

Cyanation of aryl bromides and K4[Fe(CN)6] were carried out in the presence of catalytic amounts of {[(PhCH2O)2P(CH3)2CHNCH(CH3)2]2PdCl2} (PdCl2L2) in DMF and a variety of Aromatic nitriles were obtained in good yields under aerobic conditions.

A simple methodology has been developed for the synthesis of o-phenolic-l,4-diketones from the o-phenolicl, 3-diketones. The reaction performed in the presence of organozinc reagents under mild conditions afforded the products l,4-diketones in moderate yields.

Three types of photosensitized oxygenations of α-cedrene (CED) were investigated, including: rose bengal( RB)-sensitized photooxygenation of α-cedrene in acetonitrile produced one major stereospecific product (cedr-8- exoen-9α-ol), in which the double bond migrated to an adjacent position, this result demonstrated the singlet oxygen process; 9,10-dicyanoanthrathene (DCA) sensitized photooxygenation led to the formation of cedr-8-en-10β-ol; benzyl (BZ)-sensitized photoepoxidation furnished a stereospecific 8α,9α-cedrene epoxide, this reaction includes radical reaction mechanism.

A series of novel (E)-2,3-dihydro-3-[(phenylamino)methylene]-4H-1-benzothiopyran-4-ones has been synthesized by using 2,3-dihydro-4H-1-benzothiopyran-4-ones as the starting material. The structures of the new compounds are characterized by UV-vis, IR, HRMS, 1H NMR, and 13C NMR. 2D NMR spectroscopic studies revealed that at room temperature, these compounds rather exist in the keto-enamine than in the Schiff base form. The synthesized compounds were evaluated against two species of fungi in vitro by agar double dilution method. The results of antifungal screening revealed that the MIC value of (E)-8-chloro-2,3-dihydro-3-[(4-nitrophenylamino)methylene]-4H-1-benzothiopyran-4-one (4j) against Candida albicans is 32μg· ml-1 while the control Fluconazole is 64 μg· ml-1.