Nitro group structure

The treatment of conjugated systems in terms of electron systems that extend smoothly over all atoms allows the treatment of a variety of structural phenomena, as may be explained with a spedes that shows hindered rotation and with the nitro group. 

Figure 2-52. a) Two semipolar resonance structures are needed in a correct VB representation of the nitro group, b) Representation of a nitro group by a structure having a pentavalent nitrogen atom, c) The RAMSES notation of a nitro group needs no charged resonance structures. One jr-system contains four electrons on three atoms. 

In the search for new structures with antiinflammatory activities some 1-substituted 3-dimethylaminoalkoxy-lJ/-indazoles (704) have been synthesized and pharmacologically tested (66JMC38). Doses of 20-40 mg g i.p. produced sedation, muscle relaxation and motor incoordination, whereas doses of 80-100 mg kg produced depression. Toxicity was fairly constant in all series, varying from 120 to 150 mg kg i.p., with the exception of compounds possessing a nitro group or an amino group in the indazole nucleus, which provoked cyanosis. 

From the various modifications that have been made on the phenylbutazone structure in order to increase activity and reduce toxicity it has been found that the activity persists when methyl, chloro, hydroxy or nitro groups are introduced into the para position of one or both benzene rings (see oxyphenbutazone (712) as an example). Mofebutazone (714) has also been used in Europe for several years as an antirheumatic drug. 

Treatment of l,2-difluoro-3,5-dinitrobenzene with methoxide leads to a single isomer of fluorodinitroanisole. Obtain the energies of the possible Meisenheimer complexes and predict the structure of the product. Is this outcome consistent with the previously-established directing effect of the nitro group ... 

Secondary steric effects of nitro groups are more easily detected by comparing the reactivities with those of aza derivatives. For example, in structure 20 the rate depression on passing from methyl to -butyl is only 2.5-fold and can be attributed to an inductive effect, whereas in structure 21 a similar change involves the factor 16, which can be attributed in part to steric inhibition of resonance (S.I.R.) of thep-N02 group (reaction with piperidine). 

The catalytic effect of aromatic nitro groups in the substrate and product or in an added inert nitro compoimd (e.g., w-dinitrobenzene in 18) has been observed in the reaction of 2,4-dinitrochlorobenzene with an amine in chloroform. Hydrogen bonding to benzil or to dimethyl sulfone and sulfoxide also provided catalysis. It is clear that the type of catalysis of proton transfer shown in structure 18 will be more effective when hydrogen bonding is to an azine-nitrogen. 

Intramolecular nucleophilic displacement reactions of aromatic nitro group by various nucleophiles include cydization reactions, which provide practical methods for the synthesis of a variety of heterocycles. 1 hope that the text of this review suggests a wide range of potential of this reaction in organic synthesis of various heterocycles. However, it is necessary to stress that some structural types described in this review could be prepared with similar, or even better yields by other methods. In spite of this, there are many heterocyclic systems for the synthesis of which the denitrocyclization strategy is a method of choice. 

A nitro group in the 4-position markedly increases the instability of the isoxazole ring in alkaline medium. This effect is clearly demonstrated by 3,5-dime thy 1-4-nitroisoxazole. Whereas 3,5-dimethyl-isoxazole is not affected by alkali, its 4-nitro-derivative (134) is cleaved by 2% sodium hydroxide. The structure of the product was proved by its conversion into a triazole (135) with phenyl diazonium chloride, according to the original authors. ... 

The majority of analgesics can be classified as either central or peripheral on the basis of their mode of action. Structural characteristics usually follow the same divisions the former show some relation to the opioids while the latter can be recognized as NSAlD s. The triamino pyridine 17 is an analgesic which does not seem to belong stmcturally to either class. Reaction of substituted pyridine 13 (obtainable from 12 by nitration ) with benzylamine 14 leads to the product from replacement of the methoxyl group (15). The reaction probably proceeds by the addition elimination sequence characteristic of heterocyclic nucleophilic displacements. Reduction of the nitro group with Raney nickel gives triamine 16. Acylation of the product with ethyl chlorofor-mate produces flupirtine (17) [4]. 

Most of the widely used antidepressants are tricyclics related to imipramine. A 1-phenyltetrahy-droisoquinoline analogue, nomifensine (60), departs from this structural pattern. Hiarmacologi-cally it inhibits the reuptake of catecholamines such as dopamine at neurons. It can be synthesized by alkylation of 2-nitrobenzyl-methylamine with phenacyl bromide followed by catalytic reduction of the nitro group (Pd-C) and then hydride reduction of the keto moiety to give 59. Strong acid treatment leads to cyclodehydration to nomifensine (60) [17]. 

Problem 16.7 Write resonance structures for nitrobenzene to show the electron-withdrawing reso-] nance effect of the nitro group. 

Hammett (1937) observed that the value of the constant op for a nitro group as obtained from the acidity constant of 4-nitrobenzoic acid (crp = 0.78) was applicable, for example, to the rate of hydrolysis of ethyl 4-nitrobenzoate, but not to the acidity constants of 4-nitrophenol and 4-nitroanilinium ion. These two acidities were compatible only with significantly higher constants denoted by op (1.21 and 1.27, respectively). This was (correctly) interpreted as resulting from the donor-acceptor interaction represented by the mesomeric structures 7.7. 

---