Reactivities of heterocyclic compounds during nitration

The mechanism of nitration of 2-nitro-, 3-nitro-, 1-methyl-, and 2-and 1-methyl-3-nitropyrroles in a mixture of sulfuric and nitric acids is similar to the mechanism of nitration of benzene. A 1-methyl group activates the investigated compounds only slightly.     

Reactivities of heterocyclic compounds in nitration. 5. Kinetics of nitration of 5-substituted 2-picrylaminopyridines

The kinetics of nitration of 5-bromo-, 5-chloro-, and 5-nitro-2-picrylaminopyridines in 80–96% sulfuric acid were studied by a spectrophotometric method. The kinetic parameters of nitration were calculated. The UV spectra of the neutral and protonated forms in aqueous sulfuric acid solutions were identified. It was established that the indicated compounds are nitrated in the protonated form. The relative (as compared with benzene) rates of nitration were calculated.See [1] for communication 4.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1632–1636, December, 1980.     

Reactivities of heterocyclic compounds in niration. 4. Kinetics and mechanism of nitration of 2-picrylaminopyridine in sulfuric acid

The kinetics of nitration of 2-picrylaminopyridine with nitric acid in 85– 96% sulfuric acid were studied by a spectrophotometric method. It is shown that 2-picrylaminopyridine undergoes the reaction in the protonated form. The kinetic parameters of the nitration and the relative reactivity as compared with benzene were calculated. See [1] for communication 3. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 363–365, March, 1980.     

Systematic effect of benzo-annelation on oxo-hydroxy tautomerism of heterocyclic compounds. Experimental matrix-isolation and theoretical study

Oxo-hydroxy tautomerism and phototautomerism of 2-quinolinone, 1-isoquinolinone, 3-hydroxyisoquinoline, 2-quinoxalinone, and 4-quinazolinone were studied using the matrix-isolation technique. These compounds contain a benzene ring fused with a heterocyclic ring of 2-pyridinone, 2-pyrazinone, or 4-pyrimidinone. It turned out that direct attachment of a benzene ring to a heterocycle leads to a very pronounced increase of the relative stability of oxo tautomers (in comparison with the tautomerism of the parent compounds 2-pyridinone, 2-pyrazinone, and 4-pyrimidinone). The only exception concerns 3-hydroxyisoquinoline, where fusion with a benzene ring enforces rearrangement of the double- and single-bond system in the oxo tautomer. This destabilizes substantially the oxo form with respect to the hydroxy tautomer. The ratios of population of the oxo and hydroxy tautomers observed in Ar matrixes correspond to the tautomeric equilibria of the compounds in the gas phase. These equilibria were well reproduced by theoretical calculations carried out at the QCISD and QCISD(T) levels. The combined experimental and theoretical results reveal links between aromaticity and tautomerism. Moreover, a UV-induced phototautomeric reaction transforming the oxo forms into the hydroxy tautomers was observed for all (except 3-hydroxyisoquinoline) studied compounds. This photoeffect allowed separation of the IR spectra of the tautomers in question.     

Reactivities of heterocyclic amides and thioamides

2-Alkylmercapto-4-hydroxy-3,4,5,6-tetrahydro- and 2-alkylmercapto-3,6-dihydropyrimidines were synthesized by the reaction of substituted 4-hydroxyhexahydro- and 1,2,3,6-tetrahydropyrimidine-2-thiones with alkyl halides. It is shown that the nucleophilic center in the alkylation is the sulfur atom. The capacity of the synthesized compounds for prototropic ring-chain tautomerism was established.     

Reactivity of heterocyclic compounds in nitration. 8. Nitration of 3-hydroxypyridine and its substituted forms

Nitration of 3-hydroxypyridine and its substituted forms has been studied under various conditions. It is shown that, depending on the reaction temperature and the nitrating agent, the end products of the synthesis can be 3-hydroxy-2,6-dinitropyridine or 3-hydroxy-2,4,6-trinitropyridine. The possibility of substitutional nitration of iodine derivatives of 2- and 3-hydroxypyridine is demonstrated.For Communication 7, see [1].Kazan' State Technological University, Kazan' 420015, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 958–961, July, 1998.     

Synthesis of heterocyclic compounds. II. A simple one-step synthesis of pyridines from aldehydes and malononitrile

The condensation of several aldehydes with malononitrile in the presence of a alcohol-alkoxide system provides a new simple, one-step route to 4-substituted 2-amino-3,5-dieyano-6-alkoxy-pyridines. The best results are obtained with the aromatic aldehydes. The structure of these compounds was established from a study of their infrared, ultraviolet and nuclear magnetic resonance spectra.     

Direct nitration of aldehyde arylhydrazones and the use of the products in the synthesis of some heterocyclic compounds

Direct nitration of substituted benzaldehyde p-nitrophenylhydrazones 1 gave α-nitroarylidene-p-nitrophenylhydrazines 2 . Reactions of 2 with nucleophiles result in displacement of the nitrite. Treatment of 2 with potassium thiocyanate gave 5-imino-1,3,4-Δ²-thiadiazolines 10 . Reactions of 2 with carbanions of active methylene compounds yielded the pyrazole derivatives 15–20 . 1,3-Dipolar cycloadditions of 2 onto acrylonitrile and benzalacetophenone afforded the expected cycloadducts 21 and 22 , respectively.     

Mass-spectrometer study of heterocyclic compounds

A study is made of mass-spectra of aldehydes and carboxylic acid esters of indoles. It is shown that the mass-spectra can be used to differentiate -carbonyl derivatives of indole from the -analogs.For Parts I–III see [1–3].     

Experimental and theoretical studies on the thermal decomposition of heterocyclic nitrosimines

A series of substituted 2-nitrosiminobenzothiazolines (2) were synthesized by the nitrosation of the corresponding 2-iminobenzothiazolines (6). Thermal decomposition of 2a--f and of the seleno analogue 7 in methanol and of 3-methyl-2-nitrosobenzothiazoline (2a) in acetonitrile, 1,4-dioxane, and cyclohexane followed first-order kinetics. The activation parameters for thermal deazetization of 2a were measured in cyclohexane (Delta H(++) = 25.3 +/- 0.5 kcal/mol, Delta S(++) = 1.3 +/- 1.5 eu) and in methanol (Delta H(++) = 22.5 +/- 0.7 kcal/mol, Delta S(++) = -12.9 +/- 2.1 eu). These results indicate a unimolecular decomposition and are consistent with a proposed stepwise mechanism involving cyclization of the nitrosimine followed by loss of N(2). The ground-state conformations of the parent nitrosiminothiazoline (9a) and transition states for rotation around the exocyclic C==N bond, electrocyclic ring closure, and loss of N(2) were calculated using ab initio molecular orbital theory at the MP2/6-31G* level. The calculated gas-phase barrier height for the loss of N(2) from 9a (25.2 kcal/mol, MP4(SDQ, FC)/6-31G*//MP2/6-31G* + ZPE) compares favorably with the experimental barrier for 2a of 25.3 kcal/mol in cyclohexane. The potential energy surface is unusual; the rotational transition state 9a-rot-ts connects directly to the orthogonal transition state for ring-closure 9aTS. The decoupling of rotational and pseudopericyclic bond-forming transition states is contrasted with the single pericyclic transition state (15TS) for the electrocyclic ring-opening of oxetene (15) to acrolein (16). For comparison, the calculated homolytic strength of the N--NO bond is 40.0 kcal/mol (MP4(SDQ, FC)/6-31G*//MP2/6-31G* + ZPE).     

Aromatic hydrocarbon nitration under tropospheric and combustion conditions. A theoretical mechanistic study

The viability of some nitration pathways is explored for benzene (B), naphthalene (N), and in part pyrene (P). In principle, functionalization can either take place by direct nitration (NO2 or N2O5 attack) or be initiated by more reactive species, as the nitrate and hydroxyl radicals. The direct attack of the NO2 radical on B and N, followed by abstraction of the H geminal to the nitro group (most likely accomplished by 3O2) could yield the final nitro-derivatives. Nevertheless, the initial step (NO2 attack) involves significant free energy barriers. N2O5 proves to be an even worst nitrating agent. These results rule out direct nitration at room temperature. Instead, NO3 and, even more easily, HO can form pi-delocalized nitroxy- or hydroxycyclohexadienyl radicals. A subsequent NO2 attack can produce several regio- and diastereoisomers of nitroxy-nitro or hydroxy-nitro cyclohexadienes. In this respect, the competition between NO2 and O2 is considered: the rate ratios are such to indicate that the NO3 and HO initiated pathways are the major source of nitroarenes. Finally, if the two substituents are 1,2-trans, either a HNO3 or a H2O concerted elimination can give the nitro-derivatives. Whereas HNO3 elimination is feasible, H2O elimination presents, by contrast, a high barrier. Under combustion conditions the NO2 direct nitration pathway is more feasible, but remains a minor channel.     

A theoretical study of nonlinearity in heterocyclic hydrogen-bonded complexes

Ab initio calculations are performed at the MP2/6-311++G(d,p) and DFT/B3LYP/6-311++G(d,p) theoretical levels to obtain geometries, H-bond energies and harmonic infrared vibrational properties for the Cs symmetry structures of heterocyclic hydrogen-bonded complexes, CnHmY-HX. The H-bond lengths in DFT/B3LYP calculation level are in better agreement with the experimental values than the MP2 results. The geometry optimization are interpreted in terms of hydrogen bond nonlinearity represented by theta; and phi angles, once the hydrogen bond is formed among n-electrons pairs of the heteroatom in heterocyclic and the hydrogen atom in HX. The hydrogen bond energy after of the zero-point vibrational energy (ZPE) and basis set superposition error (BSSE) corrections are overestimated at DFT/B3LYP, whereas the MP2 BSSE corrections are very large than corresponding DFT/B3LYP. For example, the BSSE corrections for the C2H4S-HNC complex are 7.60 and 0.09 kJ mol(-1) in MP2 and DFT/B3LYP calculations levels, respectively. The new vibrational modes in infrared harmonic spectrum arising from complexation show several interesting features, especially the intermolecular stretching mode.     

A theoretical study on nitration mechanism of benzene and solvent effects

Aromatic nitration is an important and canonical example of electrophilic substitution in organic chemistry. The research on nitration mechanism is also very important for synthesis of explosives since benzene molecule is a basic unit to build up into the energetic material. Besides the electrophilic substitution mechanism, there is an electron transfer mechanism[1,2]. The nitronium ion (NO+ 2), however, is a generally accepted active nitrating agent in the aromatic nitration. Therefore, the …     

Experimental and theoretical study of two-photon absorption in nitrofuran derivatives: Promising compounds for photochemotherapy

We report experimental and theoretical studies of the two-photon absorption spectrum of two nitrofuran derivatives: nitrofurantoine, (1-(5-nitro-2-furfurilideneamine)-hidantoine) and quinifuryl, 2-(5(')-nitro-2(')-furanyl)ethenyl-4-{N-[4(')-(N,N-diethylamino)-1(')-methylbutyl]carbamoyl} quinoline. Both molecules are representative of a family of 5-nitrofuran-ethenyl-quinoline drugs that have been demonstrated to display high toxicity to various species of transformed cells in the dark. We determine the two-photon absorption cross-section for both compounds, from 560 to 880 nm, which present peak values of 64 GM for quinifuryl and 20 GM for nitrofurantoine (1 GM = 1×10(-50)cm(4).s.photon(-1)). Besides, theoretical calculations employing the linear and quadratic response functions were carried out at the density functional theory level to aid the interpretations of the experimental results. The theoretical results yielded oscillator strengths, two-photon transition probabilities, and transition energies, which are in good agreement with the experimental data. A higher number of allowed electronic transitions was identified for quinifuryl in comparison to nitrofurantoine by the theoretical calculations. Due to the planar structure of both compounds, the differences in the two-photon absorption cross-section values are a consequence of their distinct conjugation lengths.     

Reactivities of aromatic compounds towards the amino radical

The reaction between hydroxylamine and a reducing ion such as V(III) or Ti(III) was studied at the dropping mercury electrode in the pH range 0–7 in presence of a substrate as benzenesulfonic acid or phenol.A method has been developed to calculate, from measurements of catalytic currents, the competition between the reducing ion and the benzene derivative for the amino radical. The strong change in the reactivities observed around pH 3 was interpreted in terms of protonation of the amino radical.The relative reactivities of the phenol and benzenesulfonic acid towards the NH·₃⁺ and NH·₃⁺ radicals were measured; assuming for the pK_a of the NH·₃⁺ radical the literature value of 3.65 the relative rate of addition of the charged and uncharged amino radical to the same aromatic substrate was obtained. An interpretation of the experimental results in terms of inductive effect is given.     

Cytotoxicity and 2D-QSAR study of some heterocyclic compounds

Herein we have studied the cytotoxicity and quantitative structure–activity relationship (QSAR) of heterocyclic compounds containing cyclic urea and thiourea nuclei. A set of 22 hydantoin and thiohydantoin related heterocyclic compounds were investigated with respect to their LC₅₀ values (Log of LC₅₀) against brine shrimp lethality bioassay in order to derive the 2D-QSAR models using MLR, PLS and ANN methods. The best predictive models by MLR, PLS and ANN methods gave highly significant square correlation coefficient (R²) values of 0.83, 0.81 and 0.91 respectively. The model also exhibited good predictive power confirmed by the high value of cross validated correlation coefficient Q² (0.74).