Molecular conformation of the racemic indan derivative (+/-)-1-trans-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-indene-1-carboxamide

This paper presents the structural characterization of the indan derivative (+/-)-1-trans-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-indene-1-carboxamide, which was unambiguously determined by X-ray diffraction (XRD) to be a racemate (R/S: 50/50) crystallizing in an achiral crystal structure (P2(1)/c, a = 9.3180(1) , b = 7.9070(2) , c = 19.7550(4) , beta = 103.250(1)A degrees, V = 1416.75(5) (3) and Z = 4). The diastereomers are related by the inversion symmetry and linked by H bond forming a dimer. The crystal packing is stabilized by hydrogen bonds, including the classical one responsible for the formation of centrosymmetric dimers, and non-classical ones involving C-H center dot center dot center dot O and C-H center dot center dot center dot pi-aryl interactions. The intra and intermolecular geometry of the title compound is compared to the (+/-)-1-trans-3-(3,4-dichlorophenyl)-2,3-dihydro-1H-indene-1-carboxylic acid one, which also present an achiral crystal structure from racemates (R/S: 50/50). The two indan derivatives crystallize in a very similar unit cell.

Síntese de indanos: uma seleção de métodos gerais e eficientes

The indan ring system is present in several compounds with important pharmacological properties. In this account recent examples of selected methods (Friedel-Crafts acylation, cycloaddition reactions, ring contraction, cyclization and resolution) for the synthesis of indans are discussed.

A dimensional analysis of the benzylic hydroxylase active site in mortierella isabellina

The spatial limits of the active site in the benzylic hydroxylase enzyme of the fungus Mortierella isabellina were investigated. Several molecular probes were used in incubation experiments to determine the acceptability of each compound by this enzyme. The yields of benzylic alcohols provided information on the acceptability of the particular compound into the active site, and the enantiomeric excess values provided information on the "fit" of acceptable substrates. Measurements of the molecular models were made using Cambridge Scientific Computing Inc. CSC Chem 3D Plus modeling program. i The dimensional limits of the aromatic binding pocket of the benzylic hydroxylase were tested using suitably substituted ethyl benzenes. Both the depth (para substituted substrates) and width (ortho and meta substituted substrates) of this region were investigated, with results demonstrating absolute spatial limits in both directions in the plane of the aromatic ring of 7.3 Angstroms for the depth and 7.1 Angstroms for the width. A minimum requirement for the height of this region has also been established at 6.2 Angstroms. The region containing the active oxygen species was also investigated, using a series of alkylphenylmethanes and fused ring systems in indan, 1,2,3,4-tetrahydronaphthalene and benzocycloheptene substrates. A maximum distance of 6.9 Angstroms (including the 1.5 Angstroms from the phenyl substituent to the active center of the heme prosthetic group of the enzyme) has been established extending directly in ii front of the aromatic binding pocket. The other dimensions in this region of the benzylic hydroxylase active site will require further investigation to establish maximum allowable values. An explanation of the stereochemical distributions in the obtained products has also been put forth that correlates well with the experimental observations.

A DFT Guided/Experimental Approach to Asymmetric Allylation and Phase-Transfer Catalysis

The Dudding group is interested in the application of Density Functional Theory (DFT) in developing asymmetric methodologies, and thus the focus of this dissertation will be on the integration of these approaches. Several interrelated subsets of computer aided design and implementation in catalysis have been addressed during the course of these studies. The first of the aims rested upon the advancement of methodologies for the synthesis of biological active C(1)-chiral 3-methylene-indan-1-ols, which in practice lead to the use of a sequential asymmetric Yamamoto-Sakurai-Hosomi allylation/Mizoroki Heck reaction sequence. An important aspect of this work was the utilization of ortho-substituted arylaldehyde reagents which are known to be a problematic class of substrates for existing asymmetric allylation approaches. The second phase of my research program lead to the further development of asymmetric allylation methods using o-arylaldehyde substrates for synthesis of chiral C(3)-substituted phthalides. Apart from the de novo design of these chemistries in silico, which notably utilized water-tolerant, inexpensive, and relatively environmental benign indium metal, this work represented the first computational study of a stereoselective indium-mediated process. Following from these discoveries was the advent of a related, yet catalytic, Ag(I)-catalyzed approach for preparing C(3)-substituted phthalides that from a practical standpoint was complementary in many ways. Not only did this new methodology build upon my earlier work with the integrated (experimental/computational) use of the Ag(I)-catalyzed asymmetric methods in synthesis, it provided fundamental insight arrived at through DFT calculations, regarding the Yamamoto-Sakurai-Hosomi allylation. The development of ligands for unprecedented asymmetric Lewis base catalysis, especially asymmetric allylations using silver and indium metals, followed as a natural extension from these earlier discoveries. To this end, forthcoming as well was the advancement of a family of disubstituted (N-cyclopropenium guanidine/N-imidazoliumyl substituted cyclopropenylimine) nitrogen adducts that has provided fundamental insight into chemical bonding and offered an unprecedented class of phase transfer catalysts (PTC) having far-reaching potential. Salient features of these disubstituted nitrogen species is unprecedented finding of a cyclopropenium based C-H•••πaryl interaction, as well, the presence of a highly dissociated anion projected them to serve as a catalyst promoting fluorination reactions. Attracted by the timely development of these disubstituted nitrogen adducts my last studies as a PhD scholar has addressed the utility of one of the synthesized disubstituted nitrogen adducts as a valuable catalyst for benzylation of the Schiff base N-diphenyl methylene glycine ethyl ester. Additionally, the catalyst was applied for benzylic fluorination, emerging from this exploration was successful fluorination of benzyl bromide and its derivatives in high yields. A notable feature of this protocol is column-free purification of the product and recovery of the catalyst to use in a further reaction sequence.

Static and dynamic bimolecular fluorescence quenching of porphyrin dendrimers in solution

The fluorescence quenching kinetics of two porphyrin dendrimer series (GnTPPH(2) and GnPZn) by different type of quenchers is reported. The microenvironment surrounding the core in GnPZn was probing by core-quencher interactions using benzimidazole. The dependence of quencher binding constant (K(a) ) on generation indicates the presence of a weak interaction between branches and the core of the porphyrin dendrimer. The similar free volume in dendrimers of third and fourth generation suggests that structural collapse in high generations occurs by packing of the dendrimer peripheral layer. Dynamic fluorescence quenching of the porphyrin core by 1,3-dicyanomethylene-2-methyl-2-pentyl-indan (PDCMI) in GnTPPH(2) is a distance dependent electron transfer process with an exponential attenuation factor beta=0.33 angstrom(-1). The quenching by 1,2-dibromobenzene occurs by diffusion process of the quencher toward to the porphyrin core, and its rate constant is practically independent of dendrimer generation.

Synthesis of arylated highly congested indans using a domino sequence

A novel and efficient regioselective synthesis of various arylated highly congested 7-aryl-5-methylsulfanylindan-4-carbonitriles (3a-(), methyl 7-aryl-5-methylsulfanylindan-4-carboxylates (lOa-e) and 7-aryl-5-methylsulfanylindan-4-carboxylic acids (lla-e) through base-catalyzed reaction of 6-aryl-4-methylsulfanyl-2-oxo-2H-pyran-3-carbonitriles (la-() and methyl 6-aryl-4-methylsulfanyl-2-oxo-2Hpyran-3-carboxylates (9a-e) by cyclopentanone (2) has been delineated. The synthetic potential of 2-pyranone was explored further to generate mo'iecular diversity using 6-aryl-4-secamino- 2-oxo-2H-pyran-3-carbonitriles (7a-h), 5,6-diaryl-4-methylsulfanyl-2-oxo2H-pyran-3-carbonitriles (Sa,b) and methyl 5,6-diaryl-4- methylsulfanyl-2-oxo-2H-pyran-3-carboxylates (12a,b) as precursors for the ring transformation by cyclopentanone to assess the effects of substituents on the course of the reaction to obtain highly congested indans, 6,7diaryl-5-methylsulfanylindan-4-carbonitriles (6a,b), 7-aryl-5-(piperidin-I-yl)indancarbonitriles (8a-h) and methyl 6,7-4- diaryl-5-methylsulfanylindan-4-carboxylate 13a,b).