Quinoline, amination nitration

Because of these difficulties, special mechanisms were proposed for the 4-nitrations of 2,6-lutidine i-oxide and quinoline i-oxide, and for the nitration of the weakly basic anilines.However, recent remeasurements of the temperature coefficient of Hq, and use of the new values in the above calculations reconciles experimental and calculated activation parameters and so removes difficulties in the way of accepting the mechanisms of nitration as involving the very small equilibrium concentrations of the free bases. Despite this resolution of the difficulty some problems about these reactions do remain, especially when the very short life times of the molecules of unprotonated amines in nitration solutions are considered... 

Cava and coworkers demonstrated that ceric ammonium nitrate oxidation of 4,6,7-trimethoxytryptamines, followed by cyclization, can efficiently generate the pyrrolo[4,3,2-de]quinoline nucleus which forms the heterocyclic core of a group of marine alkaloids which includes the makaluvamines and discorhabins. <95JOC 1800> Previous studies in this area have shown that the methoxy group can subsequently be replaced by amines to provide the natural substances. 

EtOH), were first isolated in 1872 and 1877, respectively (14). Quin-amine was observed to give indole color reactions (7, 15), and 2,3-dimethylindole was a result of zinc dust distillation of the alkaloid (15). With chromic acid (9), the quinuclidine carboxylic acid (III) was obtained, and with nitric acid 3,6,8-trinitro-4-hydroxyquinoline was isolated (15, 16). This quinoline is a consequence of fission of the indole and recyclization, with nitration preceding and following these steps [cf. ozonolysis of yohimbine to furnish a 2,3-disubstituted 4-hydroxy-quinoline (17)]. 

The first example of a low-temperature amination was reported by Bergstrom (34JA1748). He successfully aminated isoquinoline with potassium amide at room temperature in liquid ammonia. With quinoline, it was necessary to add potassium nitrate to promote amination in liquid ammonia (38JOC411). As shown in Section II,A,2, hydride-ion elimination is generally difficult. Introduction of an oxidant can sometimes lead to mild conditions for carrying out the amination. 

Amination of aromatic nitro compounds often occurs smoothly and directly also on condensation with hydroxylamine in alkaline solution, the amino group normally entering ortho or para to the nitro group. One nitro group activates naphthalene derivatives sufficiently, but in the benzene series two are necessary to induce this reaction. 2-Nitro-l-naphthylamine was thus obtained (80%) from 2-nitronaphthalene,400 and 4-nitro-l-naphthyl-amine (60%) from 1-nitronaphthylamine.401 The amino group also enters the nitrated ring of quinoline derivatives. 

Oimethyldioxirane (1) is a mild and efficient oxidant for pyridine pyridines and quinolines have also been oxidized in good yield by t-pentylhydroperoxide in the presence of molybdenum(V) chlraide. /V-Halogenation and other oxidative reactions of pyridines and related heterocycles have been re-viewed. ° Thus, pyridines and some diazines can be aminated by niesitylenesulifonylhydioxylamine (32) and similar reagents. N-Nitration of 2-picoline by nitronium tetrafluoroborate gives die (46) which is itself a nitrating agent. 

The Povarov reaction is related to the previous examples in that it can be defined as the formal imino Diels-Alder reaction between aromatic imines and electron-rich olefins. It is one of the most popular methods for the synthesis of tetrahydro-quinolines [40], and two examples of Povarov reactions in water are summarized in Scheme 1.27. In an eaily example of the use of ceric ammonium nitrate as a catalyst in synthesis [41], Perumal reported a few examples of a CAN-catalyzed Povarov reaction of aldehydes, amines and N-viitylpyrroUdin-2-ones as the olefin component in water for the synthesis of heteroaiyl-substituted tetrahydroquinolines 54 [42]. Using a different approach, Vaultier later described an onium salt-supported Povarov three-component reaction in water at room temperature affording tricyclic compounds 55. In this study, either the aldehyde or the amine components were linked to a side chain containing an onium salt, which confers solubility to the reactant [43]. 

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