Letters in Organic Chemistry - Volume 9, Issue 7, 2012

The Editorial Board wishes to dedicate this issue of Letters in Organic Chemistry to the Editor-in-Chief of the journal, Prof. Dr. Atta-ur-Rahman, FRS, on his 70th birthday. The Editorial Board acknowledges the tremendous achievements of Prof. Rahman in the fields of Organic Chemistry in general and on bioactive natural products in particular. Prof. Rahman’s honors include: the first scientist from the Muslim world to have won the prestigious UNESCO Science Prize (1999) in the 35-year old history of the Prize; elected as Fellow of Royal Society (London) in July 2006; conferred honorary doctorate degrees from many prestigious universities, including the University of Cambridge. On a national level his services are acknowledged in the form of four prestigious civil awards, including these highest national awards: Nishan-e-Imtiaz (2002), Hilal-e-Imtiaz (1998), Sitara-e-Imtiaz (1991) and Tamgha-e-Imtiaz (1983). At an academic level, Prof. Rahman has 856 publications in several fields of organic chemistry including 658 research publications, 21 patents, 114 books and 65 chapters in books published largely by major U.S. and European presses. He is currently the Editor-in-Chief of 12 scientific journals in fields ranging from Medicinal Chemistry to Pharmaceutical Drug Design. Seventy eight students have completed their Ph.D. degrees under his supervision. He chairs the Network of Academies of Sciences of Islamic Countries (NASIC) and is the Vice-President (Central & South Asia) of the Academy of Sciences for the Developing World (TWAS) Council, and Foreign Fellow of Korean Academy of Sciences. Prof. Atta-ur-Rahman was the President of the Pakistan Academy of Sciences (2003-2006) and was again elected as the President of the Academy from 1st of January 2011. In particular, Prof. Rahman has made outstanding contribution to Letters in Organic Chemistry. The contributions of Prof. Rahman to the uplifting of science in Pakistan in his capacity as the Federal Minister for Science & Technology and later as Chairman Higher Education Commission were acknowledged by a high Civil Award of the government of Austria and TWAS prize for institution building as well as by four editorials in Nature. Atta-ur-Rahman is a famous and worldwide name in chemical and biological sciences, and he merits, without any doubt, to have such a tribute in Letters in Organic Chemistry. The Editorial board wishes health and prosperity to Prof. Atta-ur-Rahman in the years to come.

Modification of nepafenac intermediate synthesis (5A) via Gassman specific ortho-substitution is reported. According to the process, 2-aminobenzophenone (1A) and 2-(methylthio)acetamide (2) were reacted in the convenient temperature conditions, in the presence of N-chlorophthalimide (3) or 1,3-dichloro-5,5-dimethylhydantoin (4), to activate the formation of azasulfonium salt and rearrangement thereof to pure 2-amino-3-benzoyl-α-(methylthio)phenylacetamide (5A). The procedure appears to be suitable for a reaction carried out in a large scale.

Herein, a selected set of chiral N1-(4-oxochromen-7-yl)-4,5-dihydro-1,2,4-triazin-6(1H)-ones (7a-k / 8a-k) were prepared via direct interaction of L-α-amino esters with N1-(4-oxochromen-7-yl) nitrile imines (generated in situ from their hydrazonoyl chloride precursors 5a,b by the action of triethylamine). These novel dihydrotriazinone-flavone hybrid compounds (7), their 2- methylchromenone analogs (8) and the L-proline homologs (9,10) were characterized by microanalytical and spectral (HRMS and NMR) data. Compounds 7a and 7i displayed good activity against (MCF-7) breast cancer.

New potentially biologically active N-bromobenzyl derivatives of α-isosparteine and 2-methylsparteine were obtained. Newly obtained compounds were characterized by IR and NMR spectroscopy. The structure of the new compounds in solution was proposed

Two series of 1,3,4-thiadiazole and 1,3,4-oxadiazole derivatives have been synthesized and characterized by elemental and spectral (IR, 1H-NMR) data. The hydrazide derivatives of 4-hydroxy quinolone and coumarin moiety were refluxed in carbon disulfide in ethanolic potassium hydroxide to obtain the corresponding hydrazinecarbodithioate salts which were then treated in two ways with (i) sulfuric acid and (ii) hydrochloric acid at cooled temperature to furnish the corresponding 1,3,4-thiadiazole and 1,3,4-oxadiazole intermediates, respectively, which were then treated with piperazine bases in the presence of formalin in methanol to furnish the final N-Mannich products 7i-10vi. The newer analogs were examined for their antimicrobial activity against five bacteria (S. aureus and B. cereus, E. coli, P. aeruginosa and K. pneumoniae) and two fungi (A. niger and C. albicans) and the results revealed that compounds demonstrated excellent activity (MICs: 3.12-25 μg/mL) as compared with the standards (MICs: 6.25-25 μg/mL).

The nucleophilic substitution reaction of hydrazono-N-(aryl)-propanehydrazonyl chlorides 7 with piperidine or morpholine, under the same reaction conditions, resulted in the formation of 1-(piperdin-1-yl / morpholine-1-yl)-N2- arylamidrazones 8a-k, respectively. The X-ray diffraction of piperidin-1-yl-N2-arylamidrazone (8b) confirmed its 1Econfiguration in agreement with the previously reported, whereas X-ray showed the unexpected 1Z-configuration of their analogs, morpholin-1-yl-N2-arylamidrazone (8j). This study established the role of hydrogen bond interaction in the stereochemistry of this class of amidrazones.

(3R,4R)-2,2,5,5-tetraphenyltetrahydrofuran-3,4-diol was employed as additive in the L-proline-catalyzed Michael addition of acetone to nitroalkenes, resulting in upgrading 8-28% ee in enantiomeric purity of the products compared with those without additives.

The preparation of substituted piperidines via three-component reaction between aldehydes, aromatic amines and acetoacetic esters has been developed. The process has been carried out under ambient conditions in the presence of zinc hydrogen sulfate [Zn(HSO4)2]. A variety of aldehydes and amines were yielded into the corresponding products demonstrating the versatility of the reaction.

Novel perylenebisimide-based fluorescent chemosensors PBI-5 and PBI-6 were designed and synthesized. Their selective recognition behavior toward metal ions was investigated by visual colorimetry and fluorescence spectroscopy. PBI-5 successfully exhibits a fluorescence turn-on response for Zn2+ and switch-off response for Cu2+ in neutral buffer solution, but the fluorescence turn-on response is moderately perturbed by Cd2+ and Pb2+. PBI-6 can effectively eliminate or weaken Pb2+ and Cd2+ induced interference and shows a better selectivity for Zn2+. Live cell imaging experiments indicates that both PBI-5 and PBI-6 can successfully enter the cell and apply in cell fluorescence imaging.

Three palladium complexes derived from diphenyl-2-pyridylphosphine (PPh2Py) were investigated for their utility as catalysts for the Suzuki-Miyaura reactions of aryl halides in environment friendly solvents such as water, alcohols etc. Good-to-excellent yields of coupling products were achieved with a wide range of aryl halides under mild reaction conditions.

The catalytic asymmetric dihydroxylation (AD) discovered by Sharpless, a Nobel Prize winner in 2001, has rapidly become an invaluable synthetic tool in the possibility of converting prochiral olefins to chiral vicinal diols. After our long-running investigation of optimized methodology for the production of stereo-defined diols based on the AD reaction, an efficient and environmentally friendly approach for the synthesis of (S)-metoprolol via AD reaction was reported. The synthetic route proceeded in four-step reactions of nucleophilic substitution, AD reaction, cyclization, and nucleophilic ring opening. The key step, AD reaction, proceeded effectively in homogeneous catalysis by using a soluble polymer chiral ligand QN-AQN-OPEG-OMe, which can be easily separated from the reaction system and reused at least four times while maintaining its high catalytic activity and enantioselectivity. This protocol has been demonstrated to produce kilogram quantities of (S)-metoprolol on scale.

A practical chemical synthesis of ethyl (R)-(-)-4-Cyano-3-hydroxybutyrate((R)-CNHB) has been accomplished from (S)-3-chloro-1,2-propanediol, which is a main by-product originating from (S,S)-Salen Co(III) catalyzed by hydrolytic kinetic resolution (HKR) of epichlorohydrin. The new synthetic approach demonstrated an efficient utilization of organic by-product for the asymmetric synthesis of the intermediate of atorvastatin.

An efficient solvent-free α-phosphoryloxylation of ketones under microwave irradiation is reported. When ketones reacted with phosphates and (diacetoxyiodo)benzene under microwave irradiation for short time, the α-phosphoryloxylaction of ketones was easily be carried out and the corresponding ketol phosphates were prepared in moderate to good yields.

Eaton's reagent efficiently catalyzed the Claisen-Schmidt condensation reaction of aryl aldehydes with aromatic and cyclic ketones under solvent free microwave irradiation conditions to afford mono and bis-chalcone derivatives. The present approach offers several advantages such as shorter reaction times, cleaner reactions, good yields, inexpensive reagent and mild reaction conditions.

Condensation of 2-acetyl-1-naphthol and 1-acetyl-2-naphthol with benzaldehydes under microwave irradiation gave chalcones or flavanones depending on the type of ketone. Also, 2-pyrazolines were synthesized by the condensation of chalcones with phenyl hydrazine under microwave irradiation in presence of dry acetic acid as a cyclizing agent. The results obtained indicated that, unlike classical heating, microwave irradiation resulted in higher yields, shorter reaction times and cleaner reactions. The structures of the synthesized compounds were elucidated using various spectroscopic methods. Theoretical studies explained the behaviour and reactivity observed for 1-acetyl-2-naphthol with benzaldehydes considering geometries, and electron densities of the formed flavanones.