Direct Reductive Cyclocondensation of the Nitro Group with the Amido Group: Key Role of the Iminophosphorane Intermediate in the Synthesis of 1,4-Dibenzodiazepine Derivatives

(+)-Complestatin 3 shows promising activity against HIV infectivity. Dale L. Boger of Scripps/La Jolla described (J. Am. Chem. Soc. 2010, 132, 7776) an elegant multicomponent assembly of 3, the key step of which was the atropisomer-selective intramolecular Larock cyclization of 1 to 2. The preparation of 1 began with the protected phenethylamine 5, prepared by Sharpless asymmetric aminohydroxylation of the styrene 4. Conversion of 5 to the areneboronic acid followed by coupling with 6 delivered 7. Acylation led to 8, with the stage set for nitro-assisted addition-elimination, to form the first bis-aryl ether of 3. The product was a mixture of atropisomers, subsequently symmetrized to 9 by removal of the nitro group. Acylation of 9 led to 1. The role of the silyl group on the alkyne of 1 was to direct the regioselectivity of the intramolecular Larock indole synthesis. Again, two atropisomers were possible from the cyclization. Earlier model studies had suggested some preference for one over the other. As it turned out, in this case the desired atropisomer was the only one observed. It is particularly striking that the coupling was efficient even in the presence of the readily reduced and unprotected chlorophenols. The modular nature of this route to (+)-complestatin 3 will make it possible to prepare a variety of analogues. As long as only the substituents on the periphery are changed, the atropisomer selectivity in the Larock cyclization should be maintained.

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Reductive Condensation of a Nitro Group with Carboxylic Acids Promoted by Phosphorus(III) Compounds: A Short Route to 5H-Dibenzo[b,e][1,4]diazepin-11(10H)-ones

Synthesis ◽

10.1055/s-0040-1707347 ◽

2020 ◽

Author(s):

Zbigniew Wróbel ◽

Michał Tryniszewski ◽

Robert Bujok ◽

Roman Gańczarczyk

Keyword(s):

Nitro Group ◽

Carboxylic Acids ◽

Carboxyl Group ◽

Short Route ◽

Step Method ◽

One Pot ◽

Aryl Group ◽

Intramolecular Condensation ◽

Reductive Condensation

Tributyl- or triphenylphosphine promotes a one-pot, three-step method for the synthesis of differently substituted dibenzodiazepinones from N-aryl-2-nitroanilines. Pyridine analogues and the corresponding thiazepinones can also be formed using this method. The process involves deoxygenation of the nitro group, then formation of an iminophosphorane intermediate and its intramolecular condensation with a carboxyl group placed in the N-aryl group. The role of the carboxyl group in the formation of the iminophosphorane and the mode of cyclization are discussed.

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ChemInform Abstract: PHOTOCHEMICAL METHOXIDE EXCHANGE IN SOME NITROMETHOXYBENZENES. ROLE OF THE NITRO GROUP IN SN2 AR REACTIONS

Chemischer Informationsdienst ◽

10.1002/chin.198211096 ◽

1982 ◽

Vol 13 (11) ◽

Author(s):

H. C. H. A. VAN RIEL ◽

G. LODDER ◽

E. HAVINGA

Keyword(s):

Nitro Group

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4,6-Dichloro-5-Nitrobenzofuroxan: Different Polymorphisms and DFT Investigation of Its Reactivity with Nucleophiles

International Journal of Molecular Sciences ◽

10.3390/ijms222413460 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13460

Author(s):

Elena Chugunova ◽

Nurgali Akylbekov ◽

Alexey Dobrynin ◽

Alexander Burilov ◽

Carla Boga ◽

...

Keyword(s):

Dft Calculations ◽

Nucleophilic Substitution ◽

Nitro Group ◽

Kinetic Data ◽

Aromatic Nucleophilic Substitution ◽

X Ray ◽

Nucleophilic Reactivity ◽

Amino Derivatives ◽

Torsional Angles

This research focuses on the X-ray structure of 4,6-dichloro-5-nitrobenzofuroxan 1 and of some of its amino derivatives (4a, 4e, 4g, and 4l) and on DFT calculations concerning the nucleophilic reactivity of 1. We have found that by changing the solvent used for crystallization, it is possible to obtain 4,6-dichloro-5-nitrobenzofuroxan (1) in different polymorphic structures. Moreover, the different torsional angles observed for the nitro group in 1 and in its amino derivatives (4a, 4e, 4g, and 4l) are strictly dependent on the steric hindrance of the substituent at C-4. DFT calculations on the course of the nucleophilic substitution confirm the role of the condensed furoxan ring in altering the aromaticity of the carbocyclic frame, while chlorine atoms strongly influence the dihedral angle and the rotational barrier of the nitro group. These results corroborate previous observations based on experimental kinetic data and give a deep picture of the reaction with amines, which proceeds via a “non-aromatic” nucleophilic substitution.

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The role of nitro groups in the binding of nitroaromatics to protein MOPC 315

Biochemical Journal ◽

10.1042/bj1730713 ◽

1978 ◽

Vol 173 (3) ◽

pp. 713-722 ◽

Cited By ~ 10

Author(s):

P Gettins ◽

D Givol ◽

R A Dwek

Keyword(s):

Hydrogen Bond ◽

Hydrogen Bonding ◽

High Resolution ◽

Hydrogen Bonds ◽

Fluorescence Quenching ◽

Nitro Group ◽

Protein Interactions ◽

Chemical Shifts ◽

Binding Constants

Two series of dinitrophenyl haptens, in which chlorine replaces one or both nitro groups, were used to investigate, by a combination of high-resolution 1H n.m.r. and fluorescence quenching, the presence of groups in the combining site of protein MOPC 315, which form hydrogen bonds to the aromatic-ring substituents of the hapten. The large differences in binding constants on successive replacement of nitro groups were shown to be due to specific hapten-substituent-protein interactions by (a) showing that there was little difference in the interaction between these haptens and 3-methylindole (a model for the residue tryptophan-93L with which the hapten stacks in protein MOPC 315), (b) proving by 1H n.m.r. that the mode of hapten binding is constant and (c) showing that the differences in Kd were consistent with the relative hydrogen-bonding capacities of chlorine and the nitro moiety. In this way it was established that each nitro group forms a hydrogen bond. Furthermore, from consideration of the 1H n.m.r. chemical shifts of several dinitrophenyl haptens and their trinitrophenyl analogues, it was shown that there is no distortion of the o-nitro group on binding to the variable fragment of protein MOPC 315.

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