Synthesis and Characterization of Far‐Red/NIR‐Fluorescent BODIPY Dyes,Solid‐State Fluorescence,and Application as Fluorescent Tags Attached to Carbon Nano‐onions

A series of π‐extended distyryl‐substituted boron dipyrromethene (BODIPY) derivatives with intense far‐red/near‐infrared (NIR) fluorescence was synthesized and characterized, with a view to enhance the dye’s performance for fluorescence labeling. An enhanced brightness was achieved by the introduction of two methyl substituents in the meso positions on the phenyl group of the BODIPY molecule; these substituents resulted in increased structural rigidity. Solid‐state fluorescence was observed for one of the distyryl‐substituted BODIPY derivatives. The introduction of a terminal bromo substituent allows for the subsequent immobilization of the BODIPY fluorophore on the surface of carbon nano‐onions (CNOs), which leads to potential imaging agents for biological and biomedical applications. The far‐red/NIR‐fluorescent CNO nanoparticles were characterized by absorption, fluorescence, and Raman spectroscopies, as well as by thermogravimetric analysis, dynamic light scattering, high‐resolution transmission electron microscopy, and confocal microscopy.     

New 2,6‐Distyryl‐Substituted BODIPY Isomers: Synthesis,Photophysical Properties,and Theoretical Calculations

A 2,6‐distyryl‐substituted boradiazaindacene (BODIPY) dye and a new series of 2,6‐p‐dimethylaminostyrene isomers containing both α‐ and β‐position styryl substituents were synthesized by reacting styrene and p‐dimethylaminostyrene with an electron‐rich diiodo‐BODIPY. The dyes were characterized by X‐ray crystallography and NMR spectroscopy and their photophysical properties were investigated and analyzed by carrying out a series of theoretical calculations. The absorption spectra contain markedly redshifted absorbance bands due to conjugation between the styryl moieties and the main BODIPY fluorophore. Very low fluorescence quantum yields and significant Stokes shifts are observed for 2,6‐distyryl‐substituted BODIPYs, relative to analogous 3,5‐distyryl‐ and 1,7‐distyryl‐substituted BODIPYs. Although the fluorescence of the compound with β‐position styryl substituents on both pyrrole moieties and one with both β‐ and α‐position substituents was completely quenched, the compound with only α‐position substituents exhibits weak emission in polar solvents, but moderately intense emission with a quantum yield of 0.49 in hexane. Protonation studies have demonstrated that these 2,6‐p‐dimethylaminostyrene isomers can be used as sensors for changes in pH. Theoretical calculations provide strong evidence that styryl rotation and the formation of non‐emissive charge‐separated S₁ states play a pivotal role in shaping the fluorescence properties of these dyes. Molecular orbital theory is used as a conceptual framework to describe the electronic structures of the BODIPY core and an analysis of the angular nodal patterns provides a reasonable explanation for why the introduction of substituents at different positions on the BODIPY core has markedly differing effects.     

Preparation of unsymmetrical distyryl BODIPY derivatives and effects of the styryl substituents on their in vitro photodynamic properties

A series of unsymmetrical distyryl BODIPYs have been prepared which function as highly potent photosensitisers with in vitro IC(50) values as low as 15 nM. Their cellular uptake, subcellular localisation and photocytotoxicity depend greatly on the styryl substituents.     

Synthesis,UV/vis spectra and electrochemical characterisation of arylthio and styryl substituted ferrocenes

Two series of substituted ferrocenes were synthesised using either the Horner-Wadsworth-Emmons reaction or monolithiation of ferrocene. The series consist of arylthio- and styryl-ferrocenes with different substituents in the para position of the aryl rings of the systems. The electronic communication was investigated by comparing the substituent effects in absorption spectroscopy and in cyclic voltammetry. A small substituent effect was found in the electronic transitions of the styryl substituted ferrocenes. The oxidation of the ferrocene derivatives showed clear substituent effects as illustrated by the linear Hammett plots. The effect was shown to be an order of magnitude larger in the arylthio-systems than in the styryl systems. It is suggested that the reason behind the large effect is a direct sulfur-iron orbital overlap.      

The mass spectra of styryl sulfoxides and sulfones

A variety of rearrangement reactions have been documented in the gas phase ion chemistry of styryl sulfoxides and sulfones. The styryl group rearranges from sulfur to oxygen as evidenced by loss of SCH₃ from methyl styryl sulfoxide and loss of SOCH₃ from the corresponding sulfone. The resulting m/e 119 ion loses carbon monoxide in one fragmentation route and alternatively loses a hydrogen atom from the aromatic nucleus to produce the benzofuran molecule ion via an electrophilic aromatic ring closure reaction. Styryl sulfoxides lose both carbon monoxide and formyl radicals directly from their molecule ions, but the corresponding sulfones do not fragment in this manner. The mechanisms of the above reactions, as well as others, were investigated using substituent and deuterium labeling. The styryl group has been shown to migrate in preference to a phenyl or substituted phenyl group by investigation of the mass spectra of appropriate aryl styryl sulfoxides and sulfones.     

Preparation and Regioselective Metalation of Bis(trimethylsilyl)methyl‐Substituted Aryl Derivatives

A range of bis(trimethylsilyl)methyl‐substituted aryl derivatives was prepared by using a Kumada–Corriu cross‐coupling reaction. The regioselective metalation of the resulting bis(trimethylsilyl)methyl‐substituted aryl derivatives bearing this bulky silyl group allowed the generation of functionalized aromatics. A regioselective switch in the presence or in the absence of the bis(trimethylsilyl)methyl group has been demonstrated. Furthermore, this silyl group was converted into a formyl group or a styryl group, enhancing the scope of application of such bis(trimethylsilyl)methyl‐substituted arenes.     

Some N-substituted 2-amino- and 2-methylquinoline-3,4-dicarboximides

The reaction of sodium 2-amino-3-cyanoquinoline-4-carboxylate and 2-methyl-3-cyanoquino-line-4-carboxylic acid in polyphosphoric acid led to 2-amino- and 2-methylquinoline-3,4-dicar-boximide, respectively. Both of these compounds undergo imide N-alkylation reactions with methyl iodide and various chloroalkylaminodialkyl amines, while the latter also condenses with 3,4-dichlorobenzaldehyde to form styryl derivatives. Although some of these compounds may be considered structural analogs of the antimalarial 4-quinolinemethanols, none exhibited antimalarial activity.     

Photoinduced transannular reaction of 1,3-dimethylcyclooctapyrimidine-2,4-diones

This article reports further elaboration of the authors' investigations on the acid-catalyzed photorearrangements undergone by derivatives of 1,3-dimethylcyclooctapyrimidine-2,4-dione. In this case the results are represented for compounds containing a simple methyl or fluorine substituent at different positions in the eight-membered ring. Upon photolysis in frozen benzene containing trifluoroacetic acid, the monomethylated compounds give varying yields of pentalenopyrimidinedione products that are not generated from the fluorinated compounds, which are either inert or undergo hydration accompanied by dehyrofluorination. Plausible mechanisms are advanced to account for the formation of the observed photoproduct species. The work represents an interesting extension and uncovered new aspects of the photorearrangement process.     

Simple and efficient access to pyrazine-2,5- and -2,6-dicarbaldehydes

Efficient two-step synthesis of pyrazine-2,5- and -2,6-dicarbaldehydes is presented that consists of transformation of easily available corresponding dimethylpyrazines to distyryl derivatives and oxidation of the latter with the tandem system of osmium tetroxide/periodate ions. The proper choice of dehydration agent in the first reaction step and the good efficiency of the subsequent low-temperature oxidation are the key points of the developed protocol. Other examined synthesis routes were much less successful, but one of them leads to new powerful routes to methyl (5-hydroxymethyl)pyrazine-2-carboxylate and dimethyl 3,4-dihydropyrazine-2,6-dicarboxylate. Previously unknown characteristics of the title compounds are reported.     

Induction of mesophases through the complexation between benzoic acids with lateral groups and polyamides containing a 2,6-diaminopyridine moiety

Supramolecular liquid crystalline polymeric complexes have been prepared by the complexation of 4-alkyloxybenzoic acid derivatives and polyamides containing a 2,6-diaminopyridine moiety. 4-Alkyloxybenzoic acids substituted by methoxy, methyl, and nitro groups at the 3-position are used for the complexation. These polymeric complexes behave as single component liquid crystalline polymers and exhibit stable and enantiotropic mesophases. In contrast, simple 4-alkyloxybenzoic acids having no substituent at the 3-position, do not form stable complexes with the polymers. For low molecular mass complexes derived from 2,6-bis(acylamino)pyridine and 4-alkyloxybenzoic acid derivatives, substituent effects are different from those for the polymeric system. In these cases, mesomorphic behaviour is observed only for the complexes based on the simple 4-alkyloxybenzoic acid and 4-alkyloxy-3-methylbenzoic acid.     

Synthesis and oxidation of 1,4-dihydroisonicotinic acid derivatives

Dimorpholinoacetic acid morpholide was used as an aldehyde in the Hantzsch synthesis, and the morpholides of the corresponding 1,4-dihydroisonicotinic acid derivatives were obtained. The direct esterification of the morpholides of the 1,4-dihydroisonicotinic acid derivatives gave their methyl, ethyl, and isopropyl esters. The oxidation of 2,6-dimethyl-3,5-dicarbethoxy-l, 4-dihydroisonicotinic acid and its morpholide with sodium nitrite occurs with cleavage, while the oxidation of the methyl esters takes place with retention of the substituent. The morpholide of 10,12-dioxo-5,10,11,12-tetrahydrodiindeno[1,2-b;2',1'-e]pyridinecarboxylic acid is oxidized with retention of the substituent.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 354–356, March, 1972.     

Diene-transmissive hetero-Diels–Alder reaction of distyryl thioketone

The reaction distyryl thioketone with donor alkenes (norbornene and styrene) gives adducts of the hetero-Diels–Alder reaction. In the case of maleic acid derivatives, a tandem reaction occurs which leads to polycyclic derivatives of 3,4-dihydro-2H-thiopyran. The stereochemical features of the ongoing transformations were examined.     

Basicity of the nitrogen atom and of the carbonyl function of methyl isonicotinate and 4-acetylpyridine. An infrared study of the interaction with proton donors

The hydrogen bonded complexes between methyl isonicotinate and 4-acetylpyridine and phenol derivatives acting as proton donors have been investigated by ir spectroscopy. The thermodynamic parameters (K, — ΔH°, — ΔS°) have been determined. The ir data show that the hydrogen bond interaction occurs at the carbonyl function and at the nitrogen atom of the ring. When the acidity of the proton donor increases, N-complexation is favoured over carbonyl complexation and with the stronger acid hydrochloric acid, only N-protonated species are observed. The data are compared with those obtained for closely related pyridine derivatives, bearing a X-C=O substituent and it is shown that the proportion of OH···N and OH···O=C species is related to the basicity of the nitrogen atom of the heterocyclic ring and to inductive and mesomeric effects depending on the nature of X.     

Tandem vicarious nucleophilic substitution of hydrogen/intramolecular Diels-Alder reaction of 1,2,4-triazines into functionalized cycloalkenopyridines

Synthesis of 2,3- and 3,4-cyclopentenopyridines, 5,6,7,8-tetrahydroquinolines and 5,6,7,8-tetrahydroisoquinolines from 1,2,4-triazine derivatives is reported. Introduction of an alpha-functionalized methyl substituent (e.g. arylsulphonyl, sulphonamide, sulphonic acid ester) into position 3- or 6- of triazines by vicarious nucleophilic substitution of hydrogen and subsequent alkylation with alkyl iodides bearing an acetylenic function in terminal position afforded valuable intermediates for intramolecular Diels-Alder reaction with inverse electron demand. When heated at higher temperature, these triazine derivatives gave the Diels-Alder cycloadducts, which, after spontaneous extrusion of nitrogen moiety, led to a variety of functionalized cycloalkenopyridine derivatives.     

Synthesis and structure-activity relationship of a new series of potent angiotensin II receptor antagonists: pyrazolo[1,5-a]pyrimidine derivatives.

We have already reported 7-oxo-4,7-dihydropyrazolo[1,5-a]pyrimidine-3-carboxylic acid derivatives, which are potent in vitro angiotensin II (AII) antagonists, but have no oral antihypertensive activity. Removal of the carboxylic acid and replacement of the heteroaromatic system afforded potent in vitro antagonists. Removal of the carbonyl oxygen and changing the position of the biphenyltetrazole substituent were critical to the display of oral activity. To improve the in vitro and oral activities, modifications were made of the substituents at the 3- and 5-positions of the pyrazolo[1,5-a]pyrimidine. Structure-activity studies showed the methyl substituent at the 3-position to be essential for potent in vivo activity. We present the design, syntheses, and biological data of a series of pyrazolo[1,5-a]pyrimidine derivatives, which are orally active AII receptor antagonists.     

An asymmetric synthesis of carboxylic acid derivatives,including lactic acid and α-amino acid derivatives,from optically active 1-chlorovinyl p-tolyl sulfoxides and ester lithium enolates with creation of chirality at the α-position

Treatment of optically active 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from symmetrical ketones or methyl formate and (R)-(−)-chloromethyl p-tolyl sulfoxide in three steps, with lithium enolate of carboxylic acid tert-butyl esters gave optically active adducts having a substituent (alkyl, alkoxy, or dibenzylamino group) at the α-position with high 1,4-chiral induction from the sulfur chiral center. The adducts were converted to optically active esters, lactic acid, and α-amino acid derivatives having a chiral center at the α-position. When this addition reaction was carried out with an ester enolate generated from excess carboxylic acid tert-butyl ester with LDA in the presence of HMPA, the diastereomer of the adduct was obtained. By using the two reaction conditions for the generation of the ester enolate, a new method for asymmetric synthesis of both enantiomers of carboxylic acid derivatives having a substituent at the α-position from the one chiral source, (R)-(−)-chloromethyl p-tolyl sulfoxide, was achieved.     

Synthesis of β-(о-hydroxybenzyl)pyridines by three-component condensation of ammonia,carbonyl-substituted 4Н-chromenes,and СН acids

Chemistry of Heterocyclic Compounds - A series of pyridine derivatives containing a 2-hydroxybenzyl or (2-hydroxynaphthalen-1-yl)methyl substituent were obtained by treating carbonyl-substituted...     

Selenium dioxide oxidation of alkylcoumarins and related methyl-substituted heteroaromatics

By the use of selenium dioxide as the specific oxidizing agent in the coumarin series, the 4-ethyl, 4-propyl and 4-benzyl substituents of coumarin were converted into α-alcohols 2 and/or ketones 3 , while 3-methyl- and 3-benzylcoumarins were converted into 3-acyl derivatives 7 . The methyl substituent of the analogous thiocoumarin 5 , chromones 10 or thiochromone 11 was also oxidized into the formyl functionality. Facile oxidative desulfurization into the ketone functionality, prior to methyl oxidation, was observed for the thione derivatives of 1a, 5, 6 and 10.     

Mass spectra of some derivatives of O-toluenesulphonic acid

The mass spectra of the derivatives of o-toluenesulphonic acid show a significant interaction of methyl and SO₂R groups. The change of a substituent mainly influences the decomposition mechanism of molecular ions and some fragment ions which are formed from them.¹     

Synthesis of 3‐(2‐benzyloxy‐6‐hydroxyphenyl)‐1‐methylpyrazoles by the reaction of chromones with methylhydrazine

The 3‐(2‐benzyloxy‐6‐hydroxyphenyl)‐5‐(methyl, phenyl or styryl)pyrazoles were prepared from the reaction of 2‐(methyl, phenyl or styryl)chromones with methylhydrazine. The structure of these compounds has been determined by several nmr techniques, and the reaction mechanism is discussed.