Simple and Selective Removal of the t‐Butyloxycarbonyl (Boc) Protecting Group on Indoles,Pyrroles, Indazoles,and Carbolines

A highly selective and efficient deprotection of the N‐t‐butoxy carbonyl (N‐Boc) group on indoles, pyrroles, indazoles, and carbolines has been achieved in high yields using a catalytic amount of NaOMe as a base in dry MeOH, at ambient temperature.     

Synthesis of a Novel Dispiroheterocyclic Framework via the Regioselective 1,3‐Dipolar Cycloaddition Reaction of Azomethine Ylides

2‐Arylidene‐1,3‐indanediones undergo regioselective 1,3‐dipolar cycloaddition with the azomethine ylide generated from acenaphthenequinone and sarcosine to afford a rare class of complex dispiropyrrolidines in good yield. Single‐crystal X‐ray crystal analysis of one of the products confirms the structure and regiochemistry of the cycloaddition.     

Synthesis of New Benzoxazaphosphinine/Benzoxazaphosphole/Diazaphosphaphenalene‐2‐sulfides using Lawesson's Reagent

Synthesis of new benzoxazaphosphinine/benzoxazaphosphole/diazaphosphaphenalene 2‐sulfides were accomplished by the reaction of Lawesson's reagent (LR) with 4‐bromo‐2‐[(phenylamino) methyl]phenol (1a), 4‐bromo‐2‐[(4‐chloro/bromo/methoxy/methylphenyl‐amino)methyl]phenol (1b–e), 4‐bromo‐2‐[(benzylamino)methyl]phenol (1f), 2‐amino‐4‐chlorophenol (2a)/2‐amino‐4‐methylphenol (2b), 1,8‐diaminonaphthalene (3) respectively in anhydrous toluene. Products 4a–f, 5a–b and 6 were characterized by IR, ¹H, ¹³C, ³¹P NMR and Mass spectra.     

Synthesis and Characterization of Metabolites and Potential Impurities of the Antiulcerative Drug Tenatoprazole

Tenatoprazole (Ulsacare^®) is a recently developed antiulcerative drug used for the treatment of both erosive and nonerosive gastroesophageal reflux disease. During the bulk synthesis of tenatoprazole, we have observed four impurities (tenatoprazole N‐oxide, tenatoprazole sulfone N‐oxide, N‐methyl tenatoprazole, and desmethoxy tenatoprazole) and two metabolites (tenatoprazole sulfide and tenatoprazole sulfone). The present work describes the synthesis and characterization of these impurities.     

A Facile Synthesis of Pyrimidone Derivatives and Single-Crystal Characterization of Pymetrozine

A facile and efficient synthetic methodology for the preparation of aza-pyrimidone and beno-pyrimidone derivatives is described, in which the triazinone ring and dihydroquinazolin-2(1H)-one was convenient constructed. The structures of all the newly synthesized compounds were characterized by mass, ¹H NMR, and infrared spectroscopy. In additional, the crystal of pymetrozine was obtained to find useful information such as configuration and molecular action mechanisms.     

Copolymerization of 2-Hydtoxypropyl Methacrylate with Alkyl Methacrylates

2-Hydroxypropyl methacrylate (2 HPMA) has been copolym-erized with ethyl methacrylate (EMA), n-butyl methacrylate (BMA), and 2-ethylhexyl methacrylate (EHMA) in bulk at 60°C using benzoyl peroxide as initiator. The copolymer composition has been determined from the hydroxyl content. The reactivity ratios have been calculated by the YBR method. For copolymerization of 2-HPMA (M₁) with EMA (M₂), the reactivity ratios are: r₁=1.807 ± 0.032, r₂=0.245 ± 0.021; with BMA (M₂) they are r₁=2.378 ± 0.001, r₂=0.19 ± 0.01; and with EHMA the values are r₁=4.370 ± 0.048, r₂=0.103 ± 0.006. Since the reactivity ratios are the measure of distribution of monomer units in a copolymer chain, the values obtained are compared and discussed. This enables us to choose a suitable copolymer for synthesizing thermoset acrylic polymers, which are obtained from cross-linking of hydroxy functional groups of HPMA units, for specific end uses.     

Microwave Assisted FriedläNder Condensation Catalyzed by Clay

Clay catalyzed Friedländer condensation of 2-amino arylaldehyde or ketone with carbonyl compounds containing α-methylene group has been achieved in solvent free condition under microwave irradiation to give polycyclic quinoline derivatives.     

Tailoring approach for exploring electron densities and electrostatic potentials of molecular crystals

Experimental and theoretical studies of electron densities and the corresponding derived entities such as electrostatic potentials have been the primary means of understanding the chemical nature and electronic properties of crystalline substances. Conventional crystal calculation methods such as the embedded cluster models are capable of performing calculations on small and medium-sized molecules, while periodic ab initio methods can treat crystals with up to 200 atoms per unit cell. A linear scaling method, viz. the molecular tailoring approach, has recently been developed for obtaining ab initio quality one-electron properties. In the present study, the molecular tailoring approach is employed to generate electron density, electrostatic potential and interaction density maps with the ibuprofen crystal as a test case. The interaction density and electrostatic potential maps produced in the present work succinctly bring out the actual crystalline environment around a given reference molecule by including the interactions with atoms in its neighborhood. The results obtained from the molecular tailoring approach may thus be expected to enhance our understanding of the environment in the crystalline material with reasonably small computational effort.Contribution to the Jacopo Tomasi Honorary Issue     

Differentiation of Boc‐protected α,δ‐/δ,α‐ and β,δ‐/δ,β‐hybrid peptide positional isomers by electrospray ionization tandem mass spectrometry

Two new series of Boc‐N‐α,δ‐/δ,α‐ and β,δ‐/δ,β‐hybrid peptides containing repeats of L ‐Ala‐δ⁵‐Caa/δ⁵‐Caa‐L ‐Ala and β³‐Caa‐δ⁵‐Caa/δ⁵‐Caa‐β³‐Caa (L ‐Ala = L ‐alanine, Caa = C‐linked carbo amino acid derived from D ‐xylose) have been differentiated by both positive and negative ion electrospray ionization (ESI) ion trap tandem mass spectrometry (MS/MS). MSⁿ spectra of protonated isomeric peptides produce characteristic fragmentation involving the peptide backbone, the Boc‐group, and the side chain. The dipeptide positional isomers are differentiated by the collision‐induced dissociation (CID) of the protonated peptides. The loss of 2‐methylprop‐1‐ene is more pronounced for Boc‐NH‐L ‐Ala‐δ‐Caa‐OCH₃ (1), whereas it is totally absent for its positional isomer Boc‐NH‐δ‐Caa‐L ‐Ala‐OCH₃ (7), instead it shows significant loss of t‐butanol. On the other hand, second isomeric pair shows significant loss of t‐butanol and loss of acetone for Boc‐NH‐δ‐Caa‐β‐Caa‐OCH₃ (18), whereas these are insignificant for its positional isomer Boc‐NH‐β‐Caa‐δ‐Caa‐OCH₃ (13). The tetra‐ and hexapeptide positional isomers also show significant differences in MS² and MS³ CID spectra. It is observed that ‘b’ ions are abundant when oxazolone structures are formed through five‐membered cyclic transition state and cyclization process for larger ‘b’ ions led to its insignificant abundance. However, b₁⁺ ion is formed in case of δ,α‐dipeptide that may have a six‐membered substituted piperidone ion structure. Furthermore, ESI negative ion MS/MS has also been found to be useful for differentiating these isomeric peptide acids. Thus, the results of MS/MS of pairs of di‐, tetra‐, and hexapeptide positional isomers provide peptide sequencing information and distinguish the positional isomers. Copyright © 2010 John Wiley & Sons, Ltd.