Quinoline production

ChemicalLand21.com (2007) Quinoline product identification webpage. http //chemicalland21.com/industrialchem/organic/QUINOLINE.htm. (last visited 8 July 2007)... 

Isatinates, obtained from the alkaline hydrolysis of isatin derivatives, are the precursors of the quinoline-4-carboxylic acids. These compounds are prepared by the Pfitzinger reaction from isatins in the presence of enolizable keto compounds in strongly alkaline medium, such as 8N KOH. In these solutions, isatinates condense with the keto compound and subsequently cyclize to the quinoline products. Recently, a modified procedure has been described, using acidic conditions. This methodology was subsequently applied to a concise manner for the preparation of derivatives of camptothecin, a topoisomerase I inhibitor23 (Scheme 115). 

With this substrate (28) the ring closure can be conveniently accomplished with either stannyl or sulfanyl radicals with no concomitant formation of the six-membered-cyclization quinoline product, which is present instead, or is predominantly formed, in all of the reaction mixtures obtained with group other than TMS. At the same time, both radical precursors, that is, stannane and thiol, can serve as nucleophiles for the intermediate indolenines 29 and 31, which are trapped to give the final substituted indoles 30 and 32 with high efficiency. 

The proposed mechanistic sequence is shown in Scheme 6.1. Because the reaction is carried out under an atmosphere of CO, carbonyl loss and addition are likely to be reversible in many of these species. For simplicity, deuterium is shown only in one ortho-aryl position so that its rearrangements can be followed. The proposed mechanism relies upon the isotopic preference for deuterium on carbon to account for the location of deuterium in the quinoline product. Commencing with the cleavage of the ortho-aryl C-D bond by Co2(CO)7 in an intramolecular complex, hydride is eliminated as DCo(CO)3 which then coordinates to and inserts into an aUyl C-C double bond. The preference for a primary Co-C bond over a secondary Co-C bond leads to deuterium incorporation selectively at the (3-position of the alkyl group to form the intermediate A. This insertion is reversible, but the isotopic... 

Scheme 54 A Skraup method for quinoline production in an acid ionic liquid.

Alternatively, a SchifTs base (53), obtained from condensation of 2-aminobenzonitrile 49 and an aryl or heteroaryl methyl ketone 52, was deprotonated with LDA, and the resulting carbanion underwent cyclization to form a 4-aminoquinoline product 54 in high yield. It is interesting that when this reaction was carried out with the ethyl ketone analog of 52 it did not produce the analogous quinoline product. Instead, it was determined that rather than undergoing deprotonation, the more sterically hindered ethyl ketone derivative underwent an addition reaction with LDA to form 55. ... 

A solution of A -arylaldimine 62 (0.4 mmol) in MeCN (1 mL) was added to a solution of Yb(OTf)3 (25 mg, 0.04 mmol) in MeCN (1 mL) and the mixture was stirred at room temperature for 10 min. Then 2-methoxypropene (1.0 mmol) was added to the mixture and stirring was continued at room temperature for 0.5 to 4 h. The mixture was quenched with 2 M HCI (1 mL) and extracted with CHCI3 (3 x 5 mL). The combined organic layer were washed with brine, dried (MgS04), and concentrated in vacuo. The residue was chromatographed on silica gel using hexane/EtOAc as eluent to give pure quinoline product. 

This important Pt system was followed up with the report of a cationic Ru-alkylidene complex (21) that provided a mixture of N-ethylaniline and quinoline products in a 1 1 mixture (Scheme 15.20) [157]. While different reaction conditions were screened with a variety of cationic Ru complexes, either preformed or generated in situ, no optimized reaction conditions that yielded the desired hydroamination product in significant excess were reported. 

The Friedlander reaction. Scheme 14, is used to prepare biologically active substituted quinolines and fused polycyclic quinolines. The HBIm containing PILs trialed for this reaction led to yields from 50 to 96%, with a good correlation between the yield, the of the anion, and the chemical shift of the proton on the cation. In contrast, the BBIm AILs with the same anions had yields of only 37—75%. [HBIm]-BF4 led to the highest yields of 90—98%, which were obtained under much milder conditions than in conventional systems. An additional advantage of the PILs was that, when unsymmetric ketones reactants were used, only the desired quinoline product formed, compared to only 80% for the AILs.142... 

The X-ray crystal structure of Rh2(02CCH3)4(IMes) (64) (Figure 9.23 IMes = l,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) was determined by Chang et al. [150]. Catalyst 64 was employed for the arylation at position 8 of quinoline (Scheme 9.21), which is a prominent structural entity in many natural products. The dirhodium tetracarboxylate itself failed to catalyze the reactions, but C-C bonded quinoline products were obtained in high yield with the dirhodium-NHC catalyst when quinoline and aryl bromide were reacted. 

The stereochemical rationale put forth for the observed stereoisomers involves examination of four transition states (I-IV). Adducts 52 and 53 would arise from the chair-like conformations I and II respectively (Scheme 2.7). The formation of 52 as the major product was anticipated since the related transition-state conformation II leading to 53 is destabilized by an eclipsing interaction between Ha and Hb. Not surprisingly, the octahydro-quinoline products, 54 and 55, derived from the two boatlike conformations, III and IV, are not detected. 

Ishii and coworkers reported that the JV-heterocyclization of naphthylamines with diols can be achieved with an iridium catalyst. In a typical example, the reaction of 1-naphthylamine with 1,3-propanediol was carried out with a catalytic amount of IrClg (5 mol%), r c-2,2 -bis(diphenylphosphino)-l,l -binaphthyl (BINAP) (10 mol%), and the corresponding 7,8-benzoquinoline was obtained in 96% yield (Scheme 11.11) [159]. The proposed reaction mechanism indicates that the imine intermediate is formed by the reaction of the amine and aldehyde by Ir-catalyzed dehydrogenation. Subsequent hydrogenation by the in situ generated Ir hydride leads to an aminoalcohol followed by cyclization to the desired quinoline products. 

Through a combined photoredox reaction, Swaminathan et al. [22] have demonstrated that Au-Ti02 can enable efficient quinoline production from nitroarenes and ethanol. Scheme 14.13 provided a tentative overview of plausible reaction mechanisms leading to the cyclization products identified by GC-MS. 

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