Group In Ortho Position Research Articles

Photochemical Transformations of Quintet m-Phenylenedinitrenes

Abstract Photochemical transformations of quintet dinitrenes have been studied for the first time by FTIR spectroscopy during the photolysis of 1,3-diazidobenzene and its 2-methyl- and 2,4,6-trimethyl-substituted derivatives in solid argon at 13 K. The reactions involve two competitive processes. In the first one, the intramolecular insertion of the nitrene unit into the 1,6-aromatic bond induces ring-opening, which leads to the formation of aminoacetylenes. The second process involves the intramolecular addition of the nitrene unit to the 1,2-aromatic bond followed by ring-opening to form 4(2H-azirin-2-ylidene)-2-butenenitrile derivatives. Methyl groups in ortho-positions to the nitrene units of quintet dinitrenes efficiently protect their aromatic ring from nitrene attacks, substantially increasing the photochemical stability of such species. However, even quintet 2,4,6-trimethylphenylene-1,3-dinitrene decomposes to ring-opened products on extended irradiation. This indicates that quintet dinitrenes are much more photochemically reactive species than triplet nitrenes. Undesirable photochemical rearrangements of the latter at early stages of the photolysis of 1,3-diazidobenzenes are suppressed on introducing the methyl group in position 2 of these azides.

An enzyme-labile safety catch linker for synthesis on a soluble polymeric support.

The development of new and broadly applicable linker groups which are stable under a variety of reaction conditions and allow release of the desired products from the solid support under very mild conditions is of great interest in organic synthesis and combinatorial chemistry. We describe an enzyme-labile safety-catch linker which releases alcohols and amines through i) enzymatic cleavage of an amino group and ii) subsequent lactam formation. The linker group was investigated on different polymeric supports: TentaGel. PEGA, CPG-beads and the soluble polymer POE-6000. From these linker-polymer conjugates 2-methoxy-5-nitrobenzyl alcohol was released by penicillin G acylase catalysed cleavage of a phenylacetamide and attack of the liberated benzylamine on the neighbouring ester group in ortho position. The model study revealed that only in the case of soluble POE-6000 conjugate high yields for the cleavage could be achieved. In the case of the other solid supports the enzyme does not have access to the interior of the polymer matrix. The application of the POE-6000 linker conjugate was investigated for various esters in Pd0-catalysed Heck-, Suzuki- and Sonogashira reactions as well as in a Mitsunobu reaction and cycloadditions. These studies proved that the linker is stable under a broad variety of reaction conditions and that the enzymatic method allows for release of the desired product alcohols under extremely mild conditions at pH 7 and 37 degrees C. In addition, the enzymatic reaction proceeds with complete chemoselectivity, that is other esters or amides are not attacked by the biocatalyst. In addition to alcohols amines can also be cleaved by means of the enzyme-initiated two-step process. In these cases the higher stability of amides as compared to esters requires warming to 60 degrees C to induce cyclization and release of the desired product.

Molecular modelling, synthesis and antitumour activity of carbocyclic analogues of netropsin and distamycin--new carriers of alkylating elements.

A series of netropsin and distamycin analogues was synthesised and investigated by molecular modelling. The lowest-energy conformations of four carbocyclic lexitropsins, potential carriers of alkylating elements, were obtained using the HyperChem 4.0 program, and compared with the DNA-lexitropsin crystal structures from the Brookhaven National Laboratory Protein Data Bank. A method for synthesis of carbocyclic lexitropsins was elaborated, with the use of a nitro group or azobenzene as precursors for the aromatic amino group. The influence of methoxy group in ortho position with respect to amide groups on the activity of the new compounds was investigated. All of the compounds tested showed high antitumour activity in the standard cell line of mammalian tumour MCF-7.

Hydrogen Bonding in Methyl-Substituted Pyridine−Water Complexes: A Theoretical Study

Density functional theory (DFT) and second-order Moller−Plesset perturbation theory (MP2) are applied to determine the hydrogen bonding interaction energies in pyridine−water and in a set of methyl-substituted pyridine−water complexes. The results show that methyl substitution stabilizes the hydrogen bond and the degree of stabilization varies with the number and the position of methyl groups. It is demonstrated that the MP2 method yields more reliable relative stabilities for these complexes than does the applied DFT method, which does not take proper account of the dispersion interactions between water and the methyl groups in ortho positions. The comparison of the order of the computed association energies of methyl-substituted pyridine−water complexes with the experimentally observed sequence of the ease of miscibility of these molecules with water shows that there is no simple relationship between the miscibility behavior and the strength of hydrogen bond formed between water and methyl derivatives o...

New feature of the phosphorescence of copper complexes ofmeso-tetraarylporphyrins

Introduction of methyl groups in orthopositions of phenyl rings of a Cu-meso-tetraphenylporphin (Cu-TPhP) molecule is shown to lead to a substantial decrease in the diffusivity of the spectrum of low-temperature (77 K) phosphorescence. It is found that the long-lived (580 μsec) and short-lived (0.7 μsec) components of Cu-TPhP phosphorescence differ in emission and absorption (phosphorescence-excitation) spectra and belong to two forms of molecules. The phosphorescence spectrum of the predominant form with small τp is diffuse, while its absorption spectrum is shifted slightly in a bathochromic manner. The phosphorescence spectrum with large τp is structural and is similar to the spectrum of Cu-meso-tetrakis-(ortho-tolyl)porphin. The difference is attributed to the nonplanarity (saddle distortion) of a Cu-TPhP molecule in the lower triplet state in the case of the form with small τp.

Autoxidation Reactions of Different Aromatic o-Aminohydroxynaphthalenes That Are Formed during the Anaerobic Reduction of Sulfonated Azo Dyes

Mono- and disulfonated naphthalene derivatives with a hydroxy group in ortho-position to an amino group are commonly occurring products of the anaerobic reduction of azo dyes by microorganisms. These substituted o-aminohydroxybenzenes and o-aminohydoxynaphthalenes are oxygen-sensitive and decompose under aerobic conditions. To evaluate their behavior under aerobic conditions, 1-amino-2-hydroxynaphthalene-6-sulfonate [AHNS; a reduction product of Sunset Yellow FCF (FDC a reduction product of Amaranth (Acid Red 27, C.I. No. 16185)], and 1,2,7-triamino-8-hydroxynaphthalene-3,6-disulfonate [TAHNDS; a reduction product of Naphthol Blue Black B (Acid Black 1, C.I. No. 20470)] were chemically prepared and exposed to air at neutral pH. The reactions were analyzed, and the autoxidation products were characterized mainly by LC−MS and UV/VIS spectroscopy. Autoxidation of AHNS led to the formation of a dimer. With AHNDS, 1,2-naphthoq...

Importance of the Conformation of Methoxy Groups on the Vibrational and Electrochemical Properties of Ubiquinones

On the basis of semiempirical calculations, the present study proposes a comprehensive interpretation of the crystallographic, vibrational, and electrochemical data on methoxy-substituted quinones, and in particular for ubiquinones, in terms of the orientation of the methoxy groups relative to the quinone ring plane. “Hindered” and “free” methoxy groups are considered depending on the presence or absence on the quinone ring of a bulky group in ortho position of the considered methoxy group, respectively. The free methoxy groups have their O−CH3 bond in the quinone ring plane while the hindered methoxy groups cannot adopt this conformation and have their methyl group tilted out of the quinone ring plane. The electron donation of the methoxy is dependent on the orientation of the O−CH3 bond and is maximum for a free methoxy group. This effect is revealed by the analysis of both electrochemical and IR data. An assignment of the ν(CO) modes of the quinones bearing such groups is proposed. From electrochemical data in literature, a new coefficient σpara, used in the Hammett equation, is determined for a hindered methoxy group (σpara = −0.07 compared to −0.27 for a free methoxy group). In the specific and biologically important case of the bulky group being another methoxy group, such as in ubiquinones (2,3-dimethoxy-substituted 1,4-benzoquinones), two types of conformation have to be considered. In the first type (conformer A), one methoxy adopts the conformation of a free methoxy group and the second that of a hindered methoxy group. In the second type (conformer B), both methoxy groups adopt the conformation of a hindered methoxy group. Both conformers appear equiprobable within the precision of our semiempirical calculations and a low rotational barrier, compared to kBT at room temperature, is found between them. Only conformers A are encountered in crystals. Using specific 13C labeling, IR data show that conformers A are mostly encountered at room temperature in solution while a mixture of both conformers is present at low temperature. On the other hand, electrochemical data on these quinones are best interpreted as the reduction of conformers B. This is explained by the higher electron affinity of conformers B compared to conformers A and by the low rotational barrier between the two conformers. Taking into account IR data of ubiquinone in the bacterial photosynthetic reaction center of Rhodobacter sphaeroides, the 70 mV difference found in the redox potential of ubiquinone in the two quinone binding sites can be explained by a difference of orientation of the methoxy groups imposed by the protein. By selecting a different orientation of the methoxy groups in the two sites, the protein would thus tune the redox potential of the quinone present in each site.

NMR and AM1 Quantum Chemical Study of the Regioselectivity of the Reaction of 2-Hydroxyethyl Methacrylate with 3-Nitrophthalic Anhydride

The reaction of 2-hydroxyethyl methacrylate with 3-nitrophthalic anhydride catalyzed with triethylamine results in the 3 : 1 mixture of two possible monoesters, the more populated one being that with the ester group in ortho position to the nitro group. The isomers were identified and quantified by 1H and 13C 1D and 2D techniques including APT, INEPT, superselective long-range (SSLR) INEPT, SSLR HHCR, COSY, NOESY, HETCOR and COLOC. Theoretical analysis was done on the model reaction of methanol with the anhydride using semiempirical AM1 quantum chemical calculations. The results indicate that the relative regioselectivity of the reaction is due to both the electron distribution in the anhydride molecule and hydrogen bonding in the stages immediately preceding the transition state.

Use of Mössbauer Spectroscopy to Study Reaction Products of Polyphenols and Iron Compounds

Abstract Mossbauer spectroscopy was used to study parameters of the reaction products of iron compounds (FeIII) and polyphenols with hydroxyl (OH) groups in ortho positions. Polyphenols used in the...

4-Ethoxymethylene-2-phenyl-5(4H)-oxazolone as a Synthon for the Synthesis of Some Fused Pyrimidines

Treatment of 4-ethoxymethylene-2-phenyl-5(4H)-oxazolone with nitrogen-containing heterocycles, having amino group in ortho position to the ring nitrogen, leads to the corresponding 4-(arylamino-methylene)-2-phenyl-5(4H)-oxazolones, which can be further converted into different fused pyrimidinones. The (z)-structure of the oxazolone exocyclic double bond has been determined on the basis of 13 C nmr spectroscopy

2,3-DIHYDROXYBENZOIC ACID AS A SUBSTRATE FOR MUSHROOM TYROSINASE2

When 2, 3-dihydroxybenzoic acid (2, 3-DBA) is acted upon by mushroom tyrosinase, a yellow intermediate, 2, 3-DBA-o-quinone, characterized by a peak at 415 nm, is the first product detected. 2, 3-DBA-o-quinone gives rise to a “final blue product” (λmax = 230, 410, 620 nm), and to “soluble oxidation product(s)” (λmax = 275–280, 350–360 nm). Kinetic data (assayed spectrophotometrically and polarographically) obtained when different concentrations of 2, 3-DBA were oxidized by a fixed amount of mushroom tyrosinase, deviated from classic Michaelis-Menten kinetics. Reduction of the “final blue product” with ascorbate resulted in the loss of the blue chromophore at 620 nm and the concomitant appearance of a “yellowish reduced final product.” The “yellowish reduced final product” could be reoxidized with either mushroom tyrosinase or with NaIO4 to the “final blue product,” indicating that the latter has carbonylic quinonoid groups in ortho position to each other.

Degradation and oligomerization of syringic acid by distinctive ecological groups of fungi

Forty-four terrestrial and aeroaquatic and aquatic fungi, including fifteen species causing white-rot, four species causing brown-rot, and some species causing soft-rot of wood, were tested for their ability to degrade the monomer syringic acid, which is released during decay of angiosperm lignin. None of the white- or brown-rot species caused any detectable degradation of syringic acid under the test conditions; however, six typical white-rot fungi strongly oligomerized syringic acid, both with and without cosubstrate. The main polymerization product was identified as a 1,3-dimethylpyrogallol oligomer by(13)C-NMR. Other minor metabolic products were methylated and hydroxylated derivatives. Oligomerization depended on the presence of 1 or 2 methoxy groups in ortho position to the hydroxy group of the substrate.Among the remaining fungi,Exophiala jeanselmei, Fusarium eumartii, andPaecilomyces variotii completely and rapidly degraded syringic acid (5 g/liter) within 48 to 100 hours. A further seven species were able to degrade syringic acid to some extent when glucose was added. Methylated and demethylated metabolic intermediates were identified by GC/MS.

Preparation and polymerization of dimethylamino(methyl)styrenes

AbstractThree isomers of methylstyrene derivatives with a dimethylamino group in ortho position to the methyl group were prepared through the coupling reaction of the corresponding Grignard reagent and vinyl bromide using a Pd(0) catalyst, and their radical and anionic polymerization was examined. Monomer reactivity ratios in the radical copolymerization with styrene indicate that 3‐dimethylamino‐4‐methylstyrene (3‐DMA‐4‐MS) and 4‐dimethylamino‐3‐methylstyrene (4‐DMA‐3‐MS) have a higher reactivity than styrene, while the reactivity of 3‐dimethyl‐amino‐2‐methylstyrene (3‐DMA‐2‐MS) is lower than that of styrene. The 13C NMR chemical shift of vinyl carbons as well as the e‐values indicate that the electron density at the vinyl carbons of 3‐DMA‐4‐MS and 4‐DMA‐3‐MS is increased by the electron donating effect of the dimethylamino group, which results in lower reactivity of the monomers in anionic polymerization. The anionic copolymerization with 1,1‐diphenylethylene gave an alternating copolymer. In the anionic polymerization of 3‐DMA‐2‐MS, proton transfer reaction from the methyl group to the propagating chain end occurred to some extent to incorporate o‐phenylene units in the chain.

SYNTHESE POLYCYCLISCHER [C]-ANELLIERTER THIOPHENE

Abstract A benzene ring substituted with two acyl groups in ortho-position was built from α-dicarbonyl compounds and dibenzyl ketone via Diels-Alder reaction of the intermediate cyclopentadienones with 1,2-diaroyl acetylenes and subsequent decarbonylation. The polycycles which were synthesized in this way formed interesting new [c]-annellated thiophenes on reaction with tetraphosphorus decasulfide (P4S10).

Synthesis and degradation of aromatic polyamides containing nitro groups

Various aromatic polyamides (aramids) which contain a nitro group at the amino substituted ring were synthesized and their thermal properties and degradation mechanisms were studied. Our present work showed that the nitro group in ortho position to the amide bond acts as an excellent leaving group for intramolecular nucleophilic displacement via the enol form to yield poly-(benzoxazole)s. Thermal decomposition of ortho-substituted aramids proceeds via a two-stage mechanism, whereas unsubstituted aramids decompose in one step. The first step represents the loss of HNO2 and the second step is due to degradation of the resulting benzoxazole polymer. Model compound and high-temperature FT-IR studies of these materials also give supportive evidences for the cyclization reaction.

Diastereoselective reactions of 1 4-bis(bromomagnesio)pentane with lactones and cyclic anhydrides

In the case of aromatic substrates, reactions of 1, 4-bis-(bromomagnesio)pentane with lactones and isatoic anhydrides proceed with a remarkable stereochemical preference leading to the formation of the trans isomer. On the other hand, those with 4H-3, 1-benzoxazin-4-ones provide mainly the cis isomer and, much more dramatic stereoselectivity has been observed in the cases of phthalic and 1, 2-naphthalene dicarboxylic anhydrides. This difference in the stereochemical control of the intramolecular Grignard reaction can be attributed to the chelation between the groups in ortho position of the intermediate oxoalkyl magnesium compound. The alkoxy and the carboxylate seem to have an opposite effect. Furthermore, reactions of 1, 4-bis(bromomagnesio)pentane with non-aromatic cyclic anhydrides yield preferentially the trans diastereoisomer.

ChemInform Abstract: Hydroxyl‐Directed Regioselective Monodemethylation of Polymethoxyarenes.

AbstractMonodemethylation of various polymethoxybenzenes, such as (I), (IV), and (VII), proceeds predominantly at the methoxyl group in ortho position to the hydroxyalkyl substituents, yielding the corresponding demethylated compounds (IIa), (Va), and (VIII) as the main products.

A chain of intramolecular hydrogen bonds, an important factor for the acidity of oligo[(2‐hydroxy‐1,3‐phenylene)methylene

AbstractThe first dissociation constant of oligonuclear phenolic compounds consisting of one nitrophenol unit besides further alkyl phenol units (10 dinuclear, 15 trinuclear, 6 tetranuclear compounds, and 4 nitrophenols as model) was determined spectroscopically in water/methanol (50/50 by vol.) at 25°C. For the ortho‐linked title compounds with the nitrophenol unit at the end of the molecule a decrease of pK1 is observed which becomes stronger with increasing chain length. The introduction of bulky groups in ortho‐position of the dissociating phenolic unit, as well as at the opposite end of the molecule causes a further decrease of pK1. The lowest value is found for a p‐nitrophenol unit in the middle of the molecule. The results do not only prove the stabilization of the monoanion by intramolecular hydrogen bonds, but they give also strong evidence for a chain of intramolecular hydrogen bonds in the undissociated molecule. The UV‐spectra of the monoanions directly show the existence of intramolecular hydrogen bonds. Especially the p‐nitrophenol system makes it possible, to differentiate according to their strength.

Blue color, metal content, and substrate binding in 4-hydroxyphenylpyruvate dioxygenase from Pseudomonas sp. strain P. J. 874.

Purified preparations of 4-hydroxyphenylpyruvate dioxygenase from Pseudomonas sp. strain P. J. 874 are blue, epsilon 595-850 approximately 2.6 +/- 0.5 (n = 6) mM-1 cm-1. Iron and zinc were the only metals detected by x-ray fluorescence of an enzyme preparation and the mean content in different preparation as determined by atomic absorption spectroscopy was determined by atomic absorption spectroscopy was 0.95 +/- 0.17 (n = 6) and 0.68 +/- 0.27 (n = 7) mol/mol 150-kilodalton tetramer, respectively. It is yet unclear if zinc is a contaminant or may be given a structural role. Results with iron chelators and reductants showed that the 595-nm absorbance is linked to enzyme-bound Fe3+ and that reduction of iron, which occurs concomitantly with disappearance of the color, is required for enzyme activity. The enol tautomer of 4-hydroxyphenylpyruvate appeared to form 2:1 a complex with enzyme-bound Fe3+, which may be the cause of the long known substrate inhibition of the enzyme. Iron chelation also seemed to be involved in the inhibition by other substrate analogues, i.e. substituted catechols and those with one phenolic hydroxyl group in ortho position to short carboxylic acid side chains. Together, substrate analogue, pH, and modification studies indicated that the tautomerizable keto group with a double bond in 3-4 position favors productive substrate binding to Fe2+ and a base with a pK alpha of approximately 6.4.

Structural dependence of nonlinear-optical properties of methyl-(2,4-dinitrophenyl)-aminopropanoate crystals

We analyze the structural relationship between microscopic and macroscopic tensors which characterize the linear- and nonlinear-optical properties of molecular crystals exhibiting a strong donor-acceptor intramolecular interaction, with particular reference to methyl-(2,4-dinitrophenyl)-aminopropanoate (MAP). The quasiplanar structure of the active part of these molecules results in a strong and characteristic anisotropy of the optical hyperpolarizabilities, which can be traced up to the macroscopic level when taking into account the crystal symmetry as well as the orientation of the molecules in the unit cell. The experimental data on MAP are thoroughly analyzed on this basis, and it is found that a two-dimensional model of the lowest-order hyperpolarizability tensor results in a structural relation between the macroscopic tensor components, which is in agreement with experimental data. In addition, the principal dielectric axes of this monoclinic crystal are determined by the orientation of the aromatic plane in the unit cell. The overall analysis also enables the determination of four independent components of the molecular hyperpolarizability tensor from experimental data only, and the results have been compared to those of a semiempirical intermediate neglect of differential overlap calculation. The anisotropy of this tensor reveals that the intramolecular charge transfer responsible for the large optical nonlinearity is predominantly from the amino group to the nitro group in para position, rather than towards the nitro group in ortho position. Finally the overall analysis provides a basis for discussing what should be the best orientation of the molecules in the unit cell for maximizing the crystal nonlinearity. The result is that phase-matchable nonlinear coefficients up to six times larger than in MAP could be observed in compounds with similar molecular hyperpolarizabilities but an optimum crystal structure.