Dinitrophenyl ethers, reactions with amine

If one limits the consideration to only that limited number of reactions which clearly belong to the category of nucleophilic aromatic substitutions presently under discussion, only a few experimental observations are pertinent. Bunnett and Bernasconi30 and Hart and Bourns40 have studied the deuterium solvent isotope effect and its dependence on hydroxide ion concentration for the reaction of 2,4-dinitrophenyl phenyl ether with piperidine in dioxan-water. In both studies it was found that the solvent isotope effect decreased with increasing concentration of hydroxide ion, and Hart and Bourns were able to estimate that fc 1/ for conversion of intermediate to product was approximately 1.8. Also, Pietra and Vitali41 have reported that in the reaction of piperidine with cyclohexyl 2,4-dinitrophenyl ether in benzene, the reaction becomes 1.5 times slower on substitution of the N-deuteriated amine at the highest amine concentration studied. 

There has been a review of relationships between activation parameters and mechanisms for biomolecular reactions in solution, including both nucleophilic substitutions and additions.5 Several studies have been reported involving substitutions by amine nucleophiles where both electronic and steric effects may be important. Kinetic studies of the reactions of 2,4-dinitrophenyl 2,4,6-trinitrophenyl ether (1) with ring-substituted... 

As is shown in Scheme 13.5, the authors found that treatment of enol ether 32 with TEA resulted in both the removal of the Boc group and hydration of the enol ether to give lactol 33. After removal of the DNs (2-(2,4-dinitrophenyl)ethoxycarbonyl) group with pyrrolidine, the hemiacetal moiety reacted with the prereleased secondary amine to produce the cyclic enamine 34. Subsequently, the Michael addition of the enamine to the unsaturated ester and Mannich reaction of the indole to the resultant iminium ion furnished the desired 35 as the sole isomer. Finally, a regioselective dehydration and stereoselective epoxidation, followed by a deprotection step, gave the desired lower segment (-)-taberhanine, which was used for the total synthesis of conophylline. 

In the reaction of aryloxypyridines with amines, the aryl group is in competition with the pyridine ring for the nucleophile. In fact, 3- and 4-(4 -nitrophenoxy) pyridine in reaction with piperidine give 3- and 4-hydroxy-pyridine and N-(4 -nitrophenyl)piperidine. Dinitrophenyl ethers behave similarly707, It would be interesting to know quantitatively the relative success of the pyridyl and aryl groups in these competitive reactions. 

Arylations are commoner than alkylations. Ullmann and Nadai s preparation of dinitrochlorobenzenes, and its extension to that of diphenyl ethers—reactions in which the nucleophiles are chloride ions and phenols, respectively—have been mentioned already (p. 268). Applied to l-(2,4-dinitronaphthyl)pyridinium chloride, the reaction gives l-chloro-2,4-dinitronaphthalene, and the same salt reacts with water to give the naphthol, with hydrogen sulphide to yield the thionaphthol, and with carboxylic acids to form dinitronaphthyl esters . Amines , alcohols , mercaptans and thiophenols have been dinitrophenylated with pyridinium salts. Styrylpyridinium salts give N-styrylpiperidine with piperidine . 

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. 

As base. Numerous reactions that are initiated by deprotonation have been conducted with KF-AI2O3. These include the synthesis of diaryl ethers, amines, and sulfides by nucleophilic aromatic substitutions, AJ-alkylation of 2,4-dinitrophenyl-hydrazones, condensation of 3-phenylisoxazol-5-one with aldehydes, and ring closure of /V-(w-chloroalkyl) carboxamides to afford 1,3-oxazolines and 1,3-oxazines. ... 

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