Nitrofluorobenzene

Properties attributed to the intermediate complex from reaction of 4-nitrofluorobenzene with azide ion were found later to be due to an artifact resulting from photolytic decomposition of the... 

TABLE 27. Rate constants (dm3 mol 1 s 1) for the reactions of 2-cyano- and 2-trifluoromethyl-4-nitrofluorobenzenes and 2-cyano-4-nitrophenylphenyl ether with some amines in aprotic solvents at... 

The activation energy, AG VkJ mol 1, of the SN2 replacement of fluoride by azide on 4-nitrofluorobenzene (circles, continuous line) and the SN1 solvolysis of /-butyl chloride (triangles, dashed line) as a function of the acceptor number, AN, of the solvent (Parker et al. 1978)... 

The nucleophilic reaction between two uncharged partners is strongly dependent on the polarity of the solvent (69CRVI), as exemplified by the reaction between 4-nitrofluorobenzene and piperidine (63MI1) which is — 10 times faster in dimethylsulfoxide (DMSO), DMF. or N-methylpyr-rolidone than in benzene and is furthermore base catalyzed by the piperidine (63M1I 64CB3277). As mentioned in Section 1II,B, polar solvents such as A-methylformamide, DMF, A-methylpyrrolidone or HMPA can also serve as reactants in special cases to transform nitrogen heterocycles... 

Treatment of the isoquinoline Reissert compound (2) with sodium hydride in dimethylformamide,96 with 50% aqueous sodium hydroxide-TEBA chloride,61 or with 50% aqueous sodium hydroxide-TBA chloride963 and an activated aryl halide, such as 2,4-dinitrofluorobenzene,96 2-bromo-3-nitropyridine,96 4-nitrochlorobenzene,61 t-butyl 2-chloro-5-nitrobenzoate,61 2-chloro-3-nitropyridine,963 4-chloro-3-nitropyridine,96a or 9-chloroacri-dine96b leads to the arylation product 43. Arylation of the quinoline Reissert compound (1) with 4-nitrofluorobenzene in the presence of sodium hydride in dimethylformamide leads to 44.96 It should be noted that alkylation of... 

It should also be noted that there is the possibility of complications arising from reaction of the nucleophile with the solvent to give the lyate anions. For example, phenoxides may react with alcohols to form alkoxide ions, so that reaction of 4-nitrofluorobenzene with sodium phenoxide in methanol was found to give 99% of 4-nitroanisole and only 1 % of the nitrophenyl phenyl ether [58]. 

Substitutions involving anionic nucleophiles generally proceed much more rapidly in dipolar aprotic solvents, such as DMSO and DMF, than in protic solvents, such as water and methanol. For example, the substitution of fluoride ions by azide ions in 4-nitrofluorobenzene is roughly four orders of magnitude faster in DMSO than in methanol [81]. When nucleophilic attack is rate limiting, the solvation of the reactants and of the transition state for formation of the intermediate are... 

Umansky et al. [106] showed that the intensive factor (acid site strengths) dominates over the extensive factor (concentration of the active sites) in controlling acid-base properties and the catalytic activity. The conclusion was reached by comparing the activity to convert isobutane of silica-aluminas, Y, ZSM-5, MOR, and b-zeolites, as well as sulfated zirconia and SbFs-promoted silica-alumina to the acidity expressed as Ho values of the strongest acid sites, which were determined from the spectral shift of adsorbed 4-nitrotoluene and 4-nitrofluorobenzene. 

Also obtained by adding under an argon atmosphere, 60% sodium hydride in oil to a mixture of 4-nitrofluorobenzene, 3-methoxybenzaldehyde and 1,3,4,5-tetram-ethylimidazolium iodide in DMF. The mixture was stirred at -15° for 15 min then at -5° for 2 h (70%) [1641]. 

Display electrostatic potential maps for phenyl fluoride, para-nitrofluorobenzene and 2,4,6-trinitrofluorobenzene. Which should be the most susceptible toward nucleophiUc attack Which should be the least susceptible Explain. 

Is para-nitrofluorobenzene more or less susceptible to attack by methoxide than fluorobenzene Calculate the energetics of the reaction. (Energies for phenyl fluoride and para-nitrofluorobenzene methoxide anion adducts are available.)... 

Electrostatic potential map for para-nitrofluorobenzene shows positively-charged regions (in blue) as likely sites for nucleophilic attack. 

The number of reactions that fit into this second class are manifold. Some typical examples are the amine-catalyzed reactions of 2,4-dinitrochlorobenzene with n-butylamine in chloroform (k"/k = 2.59 l.mole-1)23, with allylamine in chloroform (k"jk — 4.60 l.mole-1)24 and with allylamine in ethanol (k"fk =0.36 l.mole-1)25 and the amine-catalyzed reaction of p-nitrofluorobenzene with piperidine in polar solvents (k"/k < 3.2 l.mole-1)26. A typical example of a strongly catalyzed system is the reaction of 2,4-dinitrophenyl phenyl ether with piperidine in 60 % dioxan-40 % water27. 

Manetz, T.C., Pettit, D.A. and Meade, B.J., The determination of draining lymph node cell cytokine mRNA levels in BALB/c mice following dermal sodium lauryl sulfate, di-nitrofluorobenzene, and toluene diisocyanate exposure. Toxicol. Appl. Pharm., 171, 174, 2001. 

The main interaction of the complex of equilibrium 31 is probably a hydrogen bonding interaction between nitrofluorobenzenes and some amines. These complexes are more stable when the nitro groups are in position 2 of fluorobenzene than when they are in position 4. A reasonable explanation of this trend is the interaction of the ortho nitro group with the amine shown in 110, in which a second hydrogen bond (between the amino and the nitro groups) enhances the interaction. 

For n-butylamine, the -nitrofluorobenzene -nitrofluorobenzene ratio equals whUe for the secondary amine piperidine the ratio is higher ( c2-mtrofluorobenzene c4-mtrofluorobenzene = 9). This supports an interaction between the two nitrogen atoms as shown in 111, where the nitrogen of the amine is the electron donor and the nitrogen of the nitro group is the electron acceptor. 

Two of three nitrofluorobenzene isomers react with methoxide, but the third is unreactive. Obtain energies of methoxide anion (at left), ortho, meta and para-nitrofluorobenzene, and the corresponding ortho, meta and para-methoxide anion adducts (so-called Meisenheimer complexes). Calculate the energy of methoxide addition to each of the three substrates. Which substrate is probably unreactive What is the apparent directing effect of a nitro group Does a nitro group have the same effect on nucleophilic aromatic substitution that it has on electrophilic aromatic substitution (see Chapter 13, Problem 4) Examine the structures and electrostatic potential maps of the Meisenheimer complexes. Use resonance arguments to rationalize what you observe. 

Display electrostatic potential maps for phenyl fluoride, para-nitrofluorobenzene and 2,4,6-trinitrofluorobenzene. 

Studies with the reagent 4-sulfonyloxy-2-nitrofluorobenzene at 28° again showed major reaction at Lys 41 but at a rate about equal to that at the a-amino group (109, 110). No reaction was observed at Lys 7. The pKa of the other 9 lysine residues was 10.1 in agreement with titration data. In the thermal transition region above 50° the behavior of Lys 41 approached that of the other normal lysine residues. 

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