Regioorientation in the reaction of side chain activated alkylpyridines with electrophiles

X-ray structural data has shown that condensation of sym-3-nitrocollidine with benzaldehyde occurs at the 6-methyl group. The presence of an acceptor group in the side chain of 2,6-dimethyl-4-cyanomethyl-3-nitropyridine causes condensation to occur at the activated methylene group in the 4-position.M. V. Lomonosov State University, Moscow 119899. A. N. Nesmeyanov Institute of Organoelemental Compounds, Moscow 117813. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11. pp. 1543–1550, November, 1995. Original article submitted June 10, 1995.     

Ionic photodissociation and ionic photosensitized dissociation of charge-transfer complexes

Flash spectroscopic and kinetic studies have been carried out on the charge-transfer complex of tetracyanoethylene with tetrahydrofuran in a liquid paraffin solution at room temperature. The rise and decay curves in transient electronic absorption intensity have been observed with a common rate constant, corresponding to the anion radical of tetracyanoethylene and the triplet state of the charge-transfer complex, respectively. From the kinetic analysis it has been concluded that the ionic photodissociation of this complex takes place in its lowest excited triplet state. This dissociation mechanism has also been confirmed by employing a triplet energy transfer technique with which “ionic photosensitized-dissociation” phenomenon is observed. Furthermore, a few other examples of ionic photosensitized-dissociation are demonstrated in rigid glasses with typical weak charge-transfer complexes whose photodissociation processes are well-known.     

Nitropyridines: X. Palladium-catalyzed cross-coupling of 2-bromo-5-nitropyridine with terminal acetylenes

Substituted 5-nitro-2-ethynylpyridines were synthesized by the Sonogashira reaction of 2-bromo-5-5-nitropyridine with terminal acetylenes. Desilylation, oxidative decarbonylation, and the retro-Favorskii reaction of the cross-coupling products of 2-bromo-5-nitropyridine with trimethylsilylacetylene, prop-2-ynyl alcohol, and 2-methylbut-3-yn-2-ol, respectively, gave 2-ethynyl-5-nitropyridine. The hydration of 2-ethynyl-5-nitropyridine and 5-nitro-2-(phenylethynyl)pyridine according to Kucherov afforded 2-acetyl-5-nitropyridine and 5-nitro-2-phenacylpyridine, respectively.     

An effective new synthesis of 2-aminopyrrole-4-carboxylates

Efficient syntheses of 2-aminopyrroles are presented starting from β-dicarbonyl compounds, bromoacetonitrile, and amines. Alkylation of β-dicarbonyl compounds with bromoacetonitrile furnished α-cyanomethyl-β-dicarbonyl compounds. The condensation reaction of α-cyanomethyl-β-dicarbonyl compounds with amines catalyzed by p-TsOH affords the corresponding enamines in good yields. Base catalyzed cyclization via the addition of an amine moiety to the carbon-nitrogen triple bond of nitrile furnished 2-aminopyrroles in high yields.     

Selective one-pot synthesis of substituted pyrrole-3-phosphonates from α-cyanomethyl-β-ketoesters

A one-step synthesis of 5-alkoxypyrrole-3-phosphonates is presented starting from suitable α-cyanomethyl-β-ketophosphonates. The key step in the synthesis involves a one-pot addition and heteroannulation sequence. The zinc perchlorate-catalyzed addition of alcohols to the nitrile carbon of α-cyanomethyl-β-ketophosphonates followed by annulation furnished 5-alkoxypyrrole-3-phosphonates. The addition-annulation process is carried out in the presence of water and 4,5-dihydro-5-oxo-1H-pyrrole-3-phosphonates (pyrrolinones) are obtained in good yields.     

An efficient synthesis of 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles

Ethyl α-(dimethylaminomethylene)-2-cyanomethyl-4-phenylquinoline-3-carboxylate(2) as new synthons directed to 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitriles was obtained by the condensation of ethyl 2-cyanomethyl-4-phenylquinoline-3-carboxylate(1) and N,N-dimethylformamide dimethyl acetal(DMFDMA).Reaction of this enamine with primary amines(3) in HOAc-DMF at120 ℃then affords 2-substituted 1-oxo-1,2-dihydrobenzo[b][1,6]naphthyridine-4-carbonitrile derivatives(4) in good yields by a tandem addition-elimination-cyclization reaction.     

Design and chemical synthesis of [1,2,4]triazol[1,5-c]pyrimidin-5-yl amines, a novel class of VEGFR-2 kinase inhibitors

The Letter describes a facile approach to 7,8-dihydro[1,2,4]triazol[1,5-c]pyrimidin-5-yl amines, a novel class of potent inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). The synthetic sequence is centered around preparation of the key 3(5)-cyanomethyl-1,2,4-triazole intermediates and their Knoevenagel condensation with aromatic aldehydes. A subsequent three-step conversion of Knoevenagel adducts involving a reduction of vinyl nitriles followed by the reaction of the resulting amines with aryl isothiocyanates and cyclization of the respective thioureas yielded targeted heterocycles as a 1:1 mixture of tautomers. A representative molecule featured sound activity against VEGFR-2 in both enzymatic and cellular assays.     

Reduction of 2-amino-3- and -5-nitropyridine derivatives with hydrazine hydrate

The reactions of 2-amino-3-nitropyridine and 2-amino-5-nitropyridine with hydrazine hydrate resulted in elimination of the amino group and reduction of the nitro group with formation of 3-aminopyridine. A probable reaction mechanism involves addition of hydrazine hydrate at the N-C² bond, followed by elimination of ammonia and reduction of the nitro group to amino. 2-Amino-4-methyl-3-nitropyridine and 2-amino-5-methyl-3-nitropyridine reacted with hydrazine hydrate in a similar way.     

Synthesis of pyrido[1,2-a]benzimidazoles by cyclizative condensation of 2-halopyridines and 1,2-benzenediamines. Scope and mechanism of the reaction

The scope and mechanism of acid-catalyzed cyclizative condensation of 2-halopyridines with 1,2-benzene-diamines has been explored. The reaction requires a 2-halopyridine which is activated toward nucleophilic substitution. Evidence in favor of a mechanism involving pyridine ring opening is presented. Of three substituted 1,2-benzenediamines which were examined, the 4-nitro compound gave a single cyclization product whereas 4-chloro and 4-methy 1-derivatives gave isomeric mixtures. The structure of the product from 2-chloro-5-nitropyridine and 4-nitro-1,2-benzenediamine is shown to be 2,8-dinitropyrido[1,2-a]benz-imidazole.     

Cyanoacetylene and Its Derivatives. 29. New Data on Synthesis and Properties of Substituted 1,3-Oxathiolan-2-ones

We have determined the conditions for carrying out the reaction of 4-alkyl-4-hydroxy-2-alkynonitriles containing bulky or spirocyclic substituents with the KSCN-KHSO₄ system, leading to 5,5-dialkyl-4-cyanomethylene-1,3-oxathiolan-2-ones in quantitative yield (for this, we had to increase the reaction time and use a 10-fold excess of the hydrothiocyanating system compared with the known conditions). 5,5-Dimethyl-4-cyanomethyl-1,3-oxathiolan-2-one reacts with methanol in the presence of triethylamine (20±2°C), forming 2-cyanomethyl-4-cyanomethylene-2-[(1-methoxycarbonyloxyethyl-1-methyl)]-5,5-dimethyl-1,3-dithiolane (yield 90%).     

Structures of the intermediates formed in the ring-opening reaction of 2-chloro-3-nitropyridine

The reaction of 2-chloro-3-nitropyridine with two equivalents of hydroxide ion was studied by NMR and X-ray crystallography. On the basis of NMR coupling constants, the originally formed ring-opened intermediate is the pseudo-cis form, as predicted by the SN(ANRORC) mechanism. However, the first intermediate is unstable and isomerizes to a second intermediate, which was isolated. The pseudo-trans geometry of the second intermediate [3-pentenenitrile, 2-nitro-5-oxo, ion(-1), sodium] explains why additional base does not lead to the ring-closing reaction as observed with 2-chloro-5-nitropyridine.     

Isomer differentiation by charge inversion tandem mass spectrometry: an investigation into the structure of the ionic products from an SN(ANRORC) eeaction

Negative ion fast atom bombardment and negative ion chemical ionization tandem mass spectrometry combined with charge inversion reactions are used to confirm that 2-chloro-5nitropyridine reacts with the hydroxide ion by an S_N(ANRORC) mechanism in solution to form a ring-opened C₅H₃N₂O ₃ ^? anion that has the structure of the (M-H)^? anion of 2-nitro-4-cyano-2-butenal. The addition of excess hydroxide ion forms the expected 2-oxy5-nitropyridine anion. In the gas phase the same reaction forms only the 2-oxy-5-nitropyridine anion. High energy charge inversion is shown to be an excellent means of differentiating between these isomeric negative ions.     

Decrease of the XPS shake-up intensity on going from paranitroaniline to nitro-amino azabenzenes

The intensity of the shake-up satellites present in the solid-phase XPS spectra of paranitroaniline (1), 2-amino-5-nitropyridine (2) and 2-amino-5-nitropyrimidine (3) decreases from (1) to (3) in agreement with CNDO/S CI calculations. The HOMO—LUMO energy gap appears to be responsible for the observed trend.     

Reaction of nitriles of enyne acids with hydrazines. synthesis of cyano derivatives of 2-pyrazolines

The reaction of nitriles of enyne acids with hydrazine, alkylhydrazines, and phenylhydrazine gives 5-cyanomethyl-2-pyrazolines. The possible mechanism of the cyclization is examined.     

Ensembles of rings with a coumarin unit 1. Synthesis of 3-(2-R-thiazol-4-yl)-and 3-(4-R-thiazol-2-yl)coumarins

We have synthesized 3-(2-R-thiazol-4-yl)coumarins (R=H, CH₃, CH₂CN, Ar) by condensation of 3-(-bromoacetyl)coumarins with thioamides. We obtained 3-(4-R-thiazol-2-yl)coumarins (R=H, Ar) by several methods. By reaction of 2-cyanomethyl-4-phenylthiazole with 2-hydroxybenzaldehydes, we synthesized 2-imino-3-(4-phenylthiazol-2-yl)coumarins, which were converted to the corresponding coumarins by acid hydrolysis. For 3-(2-R-thiazol-4-yl)coumarins (R=CH₂CN), we carried out reactions with aromatic aldehydes. We propose alternative methods for synthesis of 2-[2-aryl(hetaryl)-1-cyanoethenyl]-4-(coumarin-3-yl)thiazoles.Ukrainian Pharmaceutical Academy, Kharkov 310002. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1345–1355, October, 1997.     

Synthesis of 5-Aryl-4-aroyl-3-hydroxy-1-cyanomethyl-3-pyrrolin-2-ones

5-Aryl-4-aroyl-3-hydroxy-1-cyanomethyl-3-pyrrolin-2-ones were synthesized by a three-component reaction of methyl aroylpyruvate with a mixture of aromatic aldehyde and 2-aminoacetonitrile sulfate in glacial acetic acid in the presence of anhydrous sodium acetate.     

Femtosecond studies of charge-transfer mediated proton transfer in 2-butylamino-6-methyl-4-nitropyridine N-oxide

We have unraveled the effects of an amino substituent in the ortho position on the excited-state dynamics of 4-nitropyridine N-oxide by studying the picosecond fluorescence kinetics and femtosecond transient absorption of a newly synthesized compound, 2-butylamino-6-methyl-4-nitropyridine N-oxide, and by quantum chemical calculations. Similar to the parent compound, the S(1) state of the target molecule has significant charge-transfer character and shows a large (approximately 8000 cm(-1)) static Stokes shift in acetonitrile. Analysis of the experimental and the theoretical results leads, however, to a new scenario in which this intramolecular charge transfer triggers in polar, aprotic solvents an ultrafast (around 100 fs) intramolecular proton transfer between the amino and the N-O group. The electronically excited N-OH tautomer is subsequently subject to solvent relaxation and decays with a lifetime of approximately 150 ps to the ground state.     

Interfacial charge-transfer absorption: semiclassical treatment

Optically induced charge transfer between adsorbed molecules and a metal electrode was predicted by Hush to lead to new electronic absorption features but has not been experimentally observed. However, Gerischer characterized photocurrents arising from such absorption between adsorbed metal atoms and semiconductor conduction bands. Interfacial charge-transfer absorption (IFCTA) provides information concerning the barriers to charge transfer between molecules and the metal/semiconductor and the magnitude of the electronic coupling and could thus provide a powerful tool for understanding interfacial charge-transfer kinetics. Here we provide a framework for modeling and predicting IFCTA spectra. The key feature of optical charge transfer to or from a band of electronic levels (taken to have a constant density of states and electronic coupling element) is that the absorption probability reaches half intensity at lambda + DeltaG(theta), where lambda and DeltaG(theta) are the reorganization energy and free-energy gap for the optical charge transfer, attains >90% intensity at lambda + DeltaG(theta) + 0.9 square root[4lambdak(B)T], and remains essentially constant until the top (bottom) level of the band is attained. However, when the electronic coupling and transition moment are assumed to be independent of photon energy (Mulliken-Hush model), a peaked, highly asymmetric absorption profile is predicted. We conclude that, in general, the electronic coupling between molecular adsorbates and the metal levels is so small that absorption is not detectable, whereas for semiconductors there may be intense features involving coupling to surface states.     

Photopolymerization initiated by charge-transfer complex. I. Photopolymerization of methylmethacrylate with the use of quinaldine-bromine and lutidine–bromine charge-transfer complexes as photoinitiator

Photopolymerization of MMA was carried out with quinaldine–bromine (QN–Br₂) and lutidine–bromine (LU–Br₂) charge-transfer complexes as initiators. The rate of polymerization R_p increased with rising monomer concentration and the monomer exponent was computed as unity. At first the rate of polymerization accelerated and then reduced as the initiator concentration was increased. The initiator exponent was 0.5. The reaction was carried out at three different temperatures and overall activation energy was calculated at 4.0 kcal/mol. The kinetic data and other evidence indicate that the overall polymerization takes place in a radical mechanism. A suitable mechanism is suggested.     

ReBr(CO)_5-Catalyzed Knoevenagel Condensation

Knoevenagel condensations are especially important reactions for the synthesis of alkene compounds having electron-withdrawing groups such as COR,CN,COOR,NO2 etc. Recently, transition metal hydride ruthenium1, hydride and polyhydride rhenium2, and polyhydride iridium complexes have been found to be the efficient catalysts for Knoevenagle condensation. However the mentioned-above transition metal hydride complexes are not easily prepared. In addition, all of them are oxygen and H2O-sensit…