New diphosphine systems

New bis-phosphines based on pamoic acid have been synthesised by the reaction of pamoic acid with PCl₃. Alternatively new amides were synthesised from pamoic acid and n-butylamine, using N,N′-carbonyldiimidazole as an activation agent. The reaction of these amides with phosphorus trichloride in toluene leads easily to the highly sensitive chlorophosphines which react with trimethylsilylmorpholine to give the corresponding di-phosphines. The new compounds formed from the reactions have been characterised spectroscopically and in one case by X-ray crystallography.     

Measurement of target fragments produced by 160 MeV proton beam in aluminum and polyethylene with CR-39 plastic nuclear track detectors

Production of target fragments from reactions of 160 MeV proton beams in aluminum and polyethylene was measured with CR-39 plastic nuclear track detectors (PNTD). Due to the detection limit of PNTD, primary protons cannot be detected; only low-energy short-range target fragments are registered. As a feasibility study, a so called “two step etching method” was employed to get the linear energy transfer (LET) spectra, absorbed dose, and dose equivalent. This method is discussed in this paper, together with the measured results.     

On DABAL-Me3 promoted formation of amides

The range and utility of DABAL-Me₃ couplings of methyl esters and free carboxylic acids with primary and secondary amines under a variety of conditions (reflux, sealed tube, microwave) has been compared for a significant range of coupling partners of relevance to the preparation of amides of interest in pharmaceutical chemistry. Commercial microwave reactors promote the fastest couplings and allow the use of significantly sterically hindered amines (primary and secondary) and carboxylic acids derivatives. The influence of microwave energy on the reaction system was shown to be typically related to thermal effects (over-pressuring and superheating).     

One-Pot Esterification and Amide Formation via Acid-Catalyzed Dehydration and Ritter Reactions

Esterification of carboxylic acid is achieved using acetonitrile as a water trap. Water liberated during esterification is consumed in cyanide hydrolysis, thereby driving the esterification to completion. Substrates having carboxylic acid and nitrile groups undergo intramolecular dehydration and rehydration to amido esters in the absence of acetonitrile. Cyano acids also undergo esterification and Ritter reaction in one pot when excess alcohol is used. For the first time, we have observed an interesting Ritter reaction of primary alcohols, leading to ester amide product in one pot.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

An eco-benign and highly efficient procedure for N-acylation catalyzed by heteropolyanion-based ionic liquids using carboxylic acid under solvent-free conditions

An eco-benign and highly efficient route for N-acylation of amines has been developed by treating amines with corresponding carboxylic acids in the presence of 2 mol % of heteropolyanion-based ionic liquids as catalysts under solvent-free conditions. This practical reaction could tolerate a wide range of substrates. Thus, various N-acylation products including N-acyl α-amino acid derivatives were obtained in moderate to excellent yields at 70 °C to 120 °C. Moreover, recycling studies revealed that heteropolyanion-based ionic liquids were easily reusable for this N-acylation. This method provides a green and much improved protocol over the existing methods.     

Stereochemistry of alkylated isoquinoline Reissert compounds

A series of alkylated isoquinoline Reissert compounds (2-acyl-1-alkyl-1,2-dihydroisoquinoline-1-nitriles) with either 3-H (3) or 3-CH₃ (4) substituents was examined by ¹H, ¹³C, and ¹⁹F NMR spectroscopies and X-ray crystallography. In all cases the trans-amide conformation, with reference to the carbonyl oxygen and the 3-position of the isoquinoline ring, exists exclusively in the solid state, and predominates in solution. As expected the 1-alkyl groups (isopropyl, isobutyl, benzyl) are nearly pseudo-axial or axial in all cases. In N-aroyl compounds the larger ortho-aroyl substituent lies syn to the 1-alkyl moiety in nine of the 11 cases, as revealed by X-ray crystallographic studies. In solution NMR results show that atropisomerism about the Ar/CO bond is usually rapid at room temperature, but slow at −50 °C and usually favors the syn isomer. CH?π interactions of the 3-methyl protons of 4 with the N-aroyl moieties appear to influence the atropisomerism.     

From isocyanides to trichloropyruvamides: application to a new preparation of oxamide derivatives

Isocyanides react readily with trichloroacetic acid anhydride forming stable hydrates of trichloropyruvamides. These compounds are valuable intermediates for obtaining oxamides by reaction with TMSCl/NEt₃ followed by addition of an amine.     

Synthesis of azide-fluoro-dehydrocoelenterazine analog as a photoaffinity-labeling probe and photolysis of azide-fluoro-coelenterazine

A photosensitive azide-fluoro-dehydrocoelenterazine analog (Az-F-DCT) was synthesized, starting from 4-fluorophenylacetic acid, as a photoaffinity-labeling probe in order to analyze symplectin active site. To examine the photo-reactivity of Az-F-DCT, azide-fluoro-coelenterazine analog (Az-F-CT) was used as a potent symplectin chromophore model. Photolysis of Az-F-CT in 2,2,2-trifluoroethanol afforded nitrene intermediate to give an insertion product. The structure of this product was confirmed through spectroscopic analyses particularly by using a proton/deuterium (H/D) exchange experiments with ESI-Q-TOF-MS and -MS/MS measurement.     

Organocatalytic Friedel–Crafts Alkylation/Lactonization Reaction of Naphthols with 3‐Trifluoroethylidene Oxindoles: The Asymmetric Synthesis of Dihydrocoumarins

Naphthols and 3‐trifluoroethylidene oxindoles were found to undergo an asymmetric Friedel–Crafts alkylation/lactonization reaction, catalyzed by only 2.5 mol % of a quinine‐derived squaramide catalyst, to afford the corresponding α‐aryl‐β‐trifluoromethyl dihydrocoumarin derivatives in high yields (up to 99 %) with excellent enantio‐ and diastereoselectivities (up to 98 % ee , >20:1 d.r.). Importantly, the lactonization proceeded by nucleophilic attack of the naphthol hydroxy group at the amide motif of the oxindoles under mild reaction conditions. This protocol represents a new strategy for the formation of dihydrocoumarins by an efficient intramolecular amide C−N bond‐cleavage and esterification process.