Catalytic ipso-Nitration of Organosilanes Enabled by Electrophilic N-Nitrosaccharin Reagent

Nitroaromatic compounds represent one of the essential classes of molecules that are widely used as feedstock for the synthesis of intermediates, the preparation of nitro-derived pharmaceuticals, agrochemicals, and materials on both laboratory and industrial scales. We herein disclose the efficient, mild, and catalytic ipso-nitration of organotrimethylsilanes, enabled by an electrophilic N-nitrosaccharin reagent and allows chemoselective nitration under mild reaction conditions, while exhibiting remarkable substrate generality and functional group compatibility. Additionally, the reaction conditions proved to be orthogonal to other common functionalities, allowing programming of molecular complexity via successive transformations or late-stage nitration. Detailed mechanistic investigation by experimental and computational approaches strongly supported a classical electrophilic aromatic substitution (S_EAr) mechanism, which was found to proceed through a highly ordered transition state.     

Computational study of TNT synthesis in solvated nitration reaction systems

Mononitrotoluene (MNT) was incorporated into solvated reaction systems and was subjected to subsequent nitration (electrophilic and free radical substitution) to obtain corresponding dinitrotoluene (DNT) and trinitrotoluene (TNT) products. In the electrophilic nitration system, the energy barrier of the reaction to produce o,p‐dinitrotoluene from p‐nitrotoluene was found to decrease from 62.7 to 14.7 kJ/mol to 9.2 kJ/mol in solventless, hydrated, and methanol‐solvated molecular reaction systems, respectively. Further nitration to produce TNT in related solventless and solvated systems also led to a stepwise decreasing trend in the required energy, from 297.6 to 118.6 kJ/mol to 42.8 kJ/mol. Comparative synthesis using ·NO₂ as the nitrating reagent to obtain o,p‐DNT or TNT in the hydrated system shows a lower reaction energy barrier than that of the same reaction in the solventless system. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009     

An “Ortho Effect” in Electrophilic Aromatic Nitrations: Theoretical Analysis and Experimental Validation

Usually, a π‐donor substituent acts as an ortho/para directing group in an electrophilic aromatic substitution reaction, and a π‐acceptor substituent acts as a meta directing group. Interestingly, when a π‐acceptor substituent is meta to a π‐donor substituent, certain electrophilic aromatic nitration occurs ortho to the acceptor substituent rather than para. The “ortho effect”, highlighted in various text books, has been tentatively analyzed here based on ab initio calculations. The reliability of the calculations was verified by the corresponding experimental data, including a new‐designed electrophilic aromatic nitration that also gave reasonable product distributions.     

Nitration of Porphyrin Systems: A Toolbox of Synthetic Methods

This review addresses nitration reactions of porphyrin derivatives. Simple porphyrins modifications afford valuable intermediates in this area of chemistry. They are useful materials for further transformations, as the NO₂ group introduced into parent porphyrin system increases its electrophilic character, thus allowing a broad spectrum of subsequent reactions, e. g. reduction of NO₂ to NH₂, subsequent diazotisation, nucleophilic substitution of hydrogen (in ortho-position to NO₂), a variety of cyclizations, etc. Such reactions are often utilized in the first steps of the designed syntheses, leading to attractive and useful target porphyrin molecules. This approach (via nitro-derivatives) allows synthesizing numerous porphyrin-like compounds of a high degree of complexity, and has thus become one of the methods choice. The substitution by NO₂ group can take place at all positions of the porphyrin systems: four meso-positions (5, 10, 15, 20) and eight positions β (2, 3, 7, 8, 12, 13, 17, 18). The third possibility includes the nitration in meso-aryl rings attached to positions 5, 10, 15, and 20. The latter derivatives (meso-aryl substituted ones) are a large, well-known group of synthetic porphyrins. The nitration reactions described herein follow three various mechanisms: (a) radical, (b) via π-cation radicals and π-dications, and (c) electrophilic. All the above cases are discussed in detail. According to our knowledge, this is the first such systematic account concerning these reactions.     

Enantioselective Electrophilic Aromatic Nitration: A Chiral Auxiliary Approach

Enantioselective electrophilic aromatic nitration methodology is needed to advance chirality‐assisted synthesis (CAS). Reported here is an enantioselective aromatic nitration strategy operating with chiral diester auxiliaries, and it provides an enantioselective synthesis of a C_3v‐symmetric tribenzotriquinacene (TBTQ). These axially‐chiral structures are much sought‐after building blocks for CAS, but they were not accessible prior to this work in enantioenriched form without resolution of enantiomers. This nitration strategy controls the stereochemistry of threefold nitration reactions from above the aromatic rings with chiral diester arms. Dicarbonyl‐to‐arenium chelation rigidifies the reaction systems, so that remote stereocenters position the ester‐directing groups selectively over specific atoms of the TBTQ framework. Closely guided by computational design, a more selective through‐space directing arm was first predicted with density functional theory (DFT), and then confirmed in the laboratory, to outperform the initial structural design. This enantio‐ and regioselective TBTQ synthesis opens a new pathway to access building blocks for CAS.     

Computational study of FOX‐7 synthesis in a solvated reaction system

Ethene and two kinds of nitrating reagents (HNO₃ and N₂O₅) in a variety of solvents were included in respective molecular systems, and each underwent a two‐stage electrophilic and free radical nitro‐substitution reaction to obtain the corresponding nitroethene compounds. Subsequent halogenation (using Cl₂ and Br₂) and amination (using NH₃) were then performed in solvents, also by electrophilic and radical substitution, to produce the desired 1,1‐diamino‐2,2‐dinitroethene (FOX‐7) derivatives. The reaction energy barrier in the nitration stage for obtaining each kind of mononitro ethene exhibited a stepwise decreasing trend when the reaction was carried out in H₂O‐solvated and CH₃OH‐solvated systems, no matter what nitrating agent was used. Related energy barrier data showed that the nitration reaction is more feasible in an H₂O‐solvated than a CH₃OH‐solvated system. The modeling results suggested that N₂O₅ is the better agent for nitration to proceed in water, bromine is suitable for halogenation, and the bromine derivatives are convenient for further amination in an H₂O‐solvated system. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Organophotocatalyzed Synthesis of Vinyl-SCF3 and Benzoyl-SCF3 Using a New N-(SCF3)(CF3)-Shelf-Stable Reagent

We report the photocatalyzed C−SCF₃ bond formation using a new shelf-stable PhPh-N-(SCF₃)(CF₃) reagent I in combination with 4CzIPN as organophotocatalyst under blue LED irradiation. While the synthesis of vinyl-SCF₃ is performed in the presence of bromide salts as an activator of reagent I , the synthesis of trifluoromethylthioesters was undertaken using aldehydes as starting material in the presence of a hydrogen atom transfer catalyst (HAT). Preliminary mechanistic investigations including EPR spectroscopy and cyclic voltammetry analysis shed the light on the reaction mechanisms.     

Solid-State Properties of Hexaazatriphenylenehexacarbonitrile HAT(CN)6.− Radical Anions in Crystalline Salts Containing Cryptand(M+) and Crystal Violet Cations

Crystalline {Cryptand[2.2.2](Na⁺)}{HAT(CN)₆^.−}⋅0.5C₆H₄Cl₂ ( 1 ), {Cryptand[2.2.2](K⁺)}{HAT(CN)₆^.−} ( 2 ), (CV⁺){HAT(CN)₆^.−} ( 3 ), and (CV⁺){HAT(CN)₆^.−}⋅2C₆H₄Cl₂ ( 4 ) salts (where CV⁺ is the crystal violet cation) containing hexaazatriphenylenehexacarbonitrile radical anions have been obtained. The solid-state molecular structure as well as the optical and magnetic properties of HAT(CN)₆^.− are studied. The formation of HAT(CN)₆^.− in 1 – 4 leads to the appearance of new bands in the visible range, at 694 and 740 nm. The HAT(CN)₆^.− radical anions have spin state S=1/2 and are packed in one-dimensional stacks containing the {HAT(CN)₆^.−}₂ dimers alternated with weaker interacting pairs of HAT(CN)₆^.− in 1 and nearly isolated {HAT(CN)₆^.−}₂ dimers in 2 . The {HAT(CN)₆^.−}₂ dimers are diamagnetic in 1 but they effectively mediate one-dimensional antiferromagnetic coupling of spins within the stacks with moderate exchange interaction of J/k_B = −80 K. The behaviour of salt 2 is described by a singlet–triplet model for the {HAT(CN)₆^.−}₂ dimers with an energy gap of 434(±7) K. Magnetic behaviour of both salts agree well with the data of extended Hückel calculations. Salts 3 and 4 contain isolated stacks of alternated HAT(CN)₆^.− and CV⁺ ions, and in this case, nearly paramagnetic behaviour is observed with Weiss temperatures of −1 and −7 K, respectively. Narrow Lorentzian EPR signals with g = 2.0033–2.0039 were found for the HAT(CN)₆^.− radical anions in 1 and 4 but in solution g-factor shifts to 1.9964. The electronic structure of HAT(CN)₆^.− is analysed based on X-ray diffraction data for 2 , showing a Jahn–Teller distortion of the radical anion that reduces the symmetry from D_3h to C_s and splits the initially degenerated LUMOs.     

The Chemical Behavior of Multibridged [2n] Cyclophanes

Multibridged [2_n] cyclophanes comprise a novel class of aromatic compounds, in which two benzene rings are connected by three up to a maximum of six ethano bridges. Compared to classical nonannelated arenes, their most distinct chemical property is the ease with which, particularly the higher-bridged homologs, take part in addition reactions (Diels-Alder additions, hydrogenations, and ionic additions). On the other hand, the typical regenerative behavior of aromatic molecules is not fully suppressed in the [2_n]cyclophanes as evidenced by such typical electrophilic aromatic substitution reactions as bromination, Friedel-Crafts acylation, and nitration. Besides these reactions in which the benzene rings are either destroyed or retained, reactions at and with the ethano bridges, e.g. their cleavage, isomerization, and functionalization can also occur.     

Nitration in the imidazo[1,2-a]pyrazine series. Experimental and computational results

Nitration was carried out on a series of imidazo[1,2-a]pyrazine derivatives. The reactivities of diversely substituted derivatives and of all positions of substitution were analysed and experimental results compared with ¹³-nmr data and semi empirical calculations (AMI). Although the unsubstituted heterocycle is highly resistant to nitration, electron-donating groups such as alkoxy or alkylamino on position 8 enhance the reactivity of the imidazo[1,2-a]pyrazine derivatives towards electrophilic substitution and, more specifically, nitration. The ¹³-nmr experiments, electronic distributions and Molecular Electrostatic Potential isodensity surfaces calculated on the neutral forms are in good agreement with experimental results indicating position 3 is the most reactive position towards nitration.     

Synthesis and some transformations of 2-(2′-thienyl)benzothiazole

Condensation of ortho-aminothiophenol with 2-thenoyl chloride in 1-methyl-2-pyrrolidone was used to synthesize 2-(2′-thienyl)benzothiazole. Its reactions of electrophilic (nitration, bromination, oxymethylation, formylation, acylation) and radical (nitration, arylation) substitution were studied.     

Oxygen Transfer from Inorganic and Organic Peroxides to Organic Substrates: A Common Mechanism?

In this progress report an attempt is made to rationalize, from a mechanistic point of view, the different ways in which oxygen is transferred from inorganic and organic peroxides to nucleophilic substrates, particularly olefins. Oxygen transfer from transition-metal peroxides, which is relevant to catalytic oxidations using O₂, H₂O₂ or ROOH, occurs via a cyclic or “pseudocyclic” peroxymetalation in which a dioxametallacycle is formed. Owing to the wide discrepancy between peroxymetalation and the conventional oxidation mechanism, i.e. nucleophilic attack of the substrate at the electrophilic “active oxygen”, we propose an alternative mechanism involving dioxiranes as the reactive species. The generation of dioxiranes appears to be a common denominator in the reactions of most organic peroxides e.g. peroxy acids, the reaction of electrophilic ketones with H₂O₂, or ozonizations. Oxygen transfer from dioxirane reagents probably involves the formation of a charge-transfer π-complex between the substrate and the carbon atom of the dioxirane, and the subsequent formation of a cyclic peroxidic intermediate.     

1-Methyl-2-(1′-methyl-2′-pyrrolyl)-1H-phenanthro[9,10-d]-imidazole. Synthesis and electrophilic substitution reactions

2-(1′-Methyl-2′-pyrrolyl)-1H-phenanthro[9,10-d]imidazole was synthesized by heating 9,10-phenanthrenequinone and 1-methyl-2-pyrrolecarboxaldehyde in glacial acetic acid in the presence of ammonium acetate. The reactions of electrophilic substitution (nitration, bromination, sulfonation, formylation, acylation) were studied for the product of its N-methylation in the KOH-DMSO medium. The electrophilic attack was found to affect exclusively the pyrrole ring.     

Über Synthese und Strukturbeweis von substituierten 5-Phenyl-1H-thieno[3,4—e]1,4-diazepin-2(3H)-onen

Chlorination and nitration of 5-phenyl-1H-thieno-[3.4-e]1.4-diazepin-2(3H)-one (1) are described. It is proved by unambiguous synthesis of the chloro derivative that electrophilic substitution of1 occurs in position 8. Chlorinated1 is methylated in position 1.     

Electrophilic substitution reactions in 4H-benzo[d,e,f]carbazole

The behavior of 4H-benzo[d,e,f]earbazole and its N-aeetyl derivative in various electrophilic substitution reactions (e.g. nitration, nitrosation, bromination, Friedel-Crafts acylations) has been investigated, and a number of new derivatives of this heterocycle (some of which are to be tested as potential carcinogens and enzyme-inducers) have been synthesized.     

NEW NONGEMINAL CYCLOPHOSPHAZENES

A series of new nongeminally-substituted cyclic phosphazenes with various substituents has been prepared via deprotonation-substitution reactions at the Me groups of both the cis and trans isomers of [(Me)(Ph)PN] ₃ . Treatment of [(Me)(Ph)PN] ₃ with n-BuLi followed by reaction with organic electrophilic reagents affords a variety of cyclic derivatives, [(RCH ₂ )(Ph)PN] ₃ , [R = Me, Cl, Br, I, (CH ₂ ) ₂ Br, CH ₂ CH═CH ₂ , SR, C(═O)OLi, C(═O)OMe, C(═O)OEt]. The structures of theses cis cyclic phosphazenes, which were obtained by x-ray diffraction, illustrate the basket-like shape of the molecules. Heating the cis and trans isomers of the parent [(Me)(Ph)PN] ₃ produced mixtures of cyclic trimers and tetramers. The latter were isolated and characterized by x-ray crystallography. Nanoparticles of gold and silver were prepared by reduction of metal salts with a reducing agent in the presence of selected trimers.     

A study of electrophilic substitution in the pyrrolo[2,3-d]pyrimidine ring

Several 4,5-disubstituted pyrrolo[2,3-d ]pyrimidines were prepared for the first time via electrophilic substitution, e.g. halogenation, nitration and sulfonation. PMR data for certain pyrrolo[2,3-d]pyrimidines are included which has furnished conclusive evidence that electrophilic substitution occurred at position 5. These pyrrolo[2,3-d]pyrimidines, with electron -withdrawing substituents at position 5, are of considerable interest as bases for the preparation of nucleoside derivatives related to tubercidin, toyocamcin and sangivamycin.     

The reaction of N2O4 with organic compounds

The reaction of N₂O₄ with oximes of formylimidazoles is examined. It is shown that, in addition to the conversion of the oxime group to trinitromethyl, nitration of the imidazole ring occurs including nitration in the 2-position, which is not activated towards electrophilic substitution in acid media.For part VIII, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 5, pp. 669–673, May, 1970.     

Oxidation of α-amino acids promoted by the phthalimide N-oxyl radical: A kinetic and product study

A kinetic study of the hydrogen atom transfer (HAT) reaction from a series of N-Boc- or N-Acetyl-protected amino acids to the phthalimide N-oxyl radical (PINO) was carried out to obtain information about reactivity and selectivity patterns. With amino acids containing aliphatic side chains, the 2nd order rate constants are of the same order of magnitude, in agreement with a HAT process involving the Cα?H bond. Proline is the most reactive substrate suggesting that HAT process involves the C_δ?H bond instead of C_α?H bond. These results are confirmed by the product analysis of the aerobic oxidations of the corresponding N-Boc and N-Ac protected amino acids methyl esters promoted by N-hydroxyphthalimide. Comparison of our results with those reported for HAT reactions to other radical species indicates that PINO displays electrophilic characteristics that are intermediate between those observed for the more stable Br radical and the more reactive cumyloxyl radical.     

Synthesis and reaction of 2,7-dimethylpyrrolo[1,2-A]quinoline with electrophilic reagents

2,7-Dimethylpyrrolo[1,2-a]quinoline (1) was synthesized from 2,6-dimethylquinoline and bromoaeetone via a Tsebitsehibabin reaction. The electrophilic substitution reactions of I, namely, nitrosation, acylation, diazonium coupling, formylation, bromination, and nitration were studied.