Lepidine, reactions

The easier elimination of pyridine compared to quinoline-4 may be related to the pK value of 4-methylthiazole, which is between those of lepidine and 2-picoline (25. 55). This reaction explains also why a neutrodimethine cyanine is obtained with such good yields when reacting together a quaternary salt, ketomethylene, and o-ester in a basic medium. As the reaction proceeds, the trimethine cyanine is attacked by the ketomethylene. The resulting 2-methyl quaternary salt is transformed into trimethine cyanine, consuming the totality of the ketomethylene (1, p. 512 661). The mesosubstituted neutrodimethine cyanine is practically pure. 

Table II shows that, at least for the reactions with quinoline and with 4-methylquinoline (lepidine), nickel-alumina and degassed Raney nickel catalysts are of similar efficiency but better yields have been obtained with degassed Raney nickel, and only this catalyst produces the biaryl from 7-methyIquinoIine.

Most of the reactions with quinolines and degassed Raney nickels have been carried out at the atmospheric boiling point (above 230 C), a condition which is known to favor the formation of by-products. With quinoline and 4-methylquinoline (lepidine), however, the yields of the 2,2 -biquinolines were increased three to four times by heating in vacuo at 150° C, and it seems probable that other quinolines will behave similarly. Table II also shows that the yields of 2,2 -biquino-lines obtained under comparable conditions vary with the position of the methyl group in a fashion reminiscent of the trends observed with the pyridines (Table I). This similarity extends to the behavior of the two 2-methyl substituted quinolines studied, which undergo loss of the 2-methyl group to some extent and form traces of 2,2 -biquinolines. 

A solution of A-adamantanecarbonyloxy-2-thiopyridone (145 mg, 0.5 mmol), cam-phorsulfonate salt of lepidine (1.23 g, 3.27 mmol), and dichloromethane (6 ml) was irradiated with a tungsten lamp (200 W, W-hv) under nitrogen atmosphere at the range of 20 25 °C for 1 h. After the reaction, the reaction mixture was poured into... 

To a mixture of adamantyl bromide (0.5 mmol) and trifluoroacetate salt of lepidine (2.5 mmol) in benzene (6 ml) were added (trimethylsilyl)silane (1.0 mmol) and AIBN (1.0 mmol). The mixture was heated at 80 °C for 14 h under an argon atmosphere. After the reaction, the reaction mixture was washed with sat. aq. NaHC03. The organic layer was dried over Na2S04. After removal of the solvent, the residue was chromatographed on silica gel to give 2-(l-adamantyl)-4-methylquinoline in 90% (125 mg) yield [33]. 

The reaction worked well when run to ca. 50% conversion, but has yet to be scoped as a general method for the alkenylation of heteroaromatic bases. One further example was examined involving the union of 1-methylcyclohexene and lepidine 31. In that case, elimination of benzoic acid was less favourable and the only product identified was adduct 63, formed in an unspecified yield (Scheme 14). A related metal-catalysed procedure has been described and its effectiveness is also influenced by the nature of the substrates to be coupled <83JCS(P2)531>. 

The scope of the reaction has yet to be established and may prove rather limited. When applied to 4-cyanopyridine, for example, the main product was 2-butyl-4-cyanopyridine 81 (Scheme 27). With lepidine trifluoroacetate 35, 2-n-butyllepidine 82 was formed in 25% yield (Scheme 28). 

Lemieux-Johnson oxidation, 812-813 Lepidine, 702, 1026 Lethargic reactions, 939-940 Leuchs anhydrides, 1014 DL-Leucine, 633 L-Leucine, 839, 1124 amino peptidase, 1204 ethyl ester, 88... 

The Minisci reaction has successfully been applied for the alkylation of various heteroarenes, i. e. lepidine, pyrazine, quinoline and quinoxaline [2e, 2g, 10]. Organic compounds such as alkanes, alkenes, carboxylic acids, esters, amides, amines, alcohols, ethers, aldehydes, ketones, halides etc. have been successfully used as radical precursors in the Minisci reaction. A good overview of the different methods which have been applied to generate the alkyl radicals in these processes is summarized in [10b]. 

Chlorolepidine (20 g) and potassium hydroxide (6.3 g) are dissolved in alcohol (150 ml). Raney nickel (3 g) is added and hydrogenation (1 mole of hydrogen) is carried out at room temperature and atmospheric pressure. Reaction is complete in 16 h. The catalyst is filtered off and the alcohol is removed by distillation. The residue is extracted with ether, and the extracts are washed with water, dried, and evaporated. The crude lepidine is purified by distillation. Its boiling point is 126°/40mm. The yield amounts to 94%. 

The action of acids on these anhydro bases brings about, on the one hand, cleavage to meroquinene and the corresponding lepidine, and on the other, a complicated reaction leading to the new bases, apocinchene and apo-quinene (XLVIII) (13, 56, 68, 92, 93). 

Thiazole green represents another class of carbocyanines, which was recently utilized in the low-level detection of DNA restriction fragments by Soper et al. [74]. This dye is comprised of a quinolinium and a thiazolium nucleus joined by a pen-tamethine chain. The synthetic route to the thiazole green 34 is shown in Fig. 14.7. 2-Methylbenzothiazole 29 was allowed to react with methyl iodide to give the N-methyl derivative 30 which was further treated with malonaldehyde-dianil hydrochloride to afford the intermediate product 31. The intermediate product 31 was then allowed to react with N-(3-iodopropyl)lepidinium iodide 33, which had been obtained from the reaction of lepidine with 1,3-diiodopropane, to finally afford the asymmetrical thiazole green 34. 

This reaction was reported first by Ruzicka et al. in 1924 and was extended by Ainley and King in 1935. It is a multistep synthesis of a-piperidyl-4-quinolinemethanols (or quinolyl-4-a -piperidylcarbinols" ), involving the reaction of (a) amidation of p-anisidineby an acetoacetic ester, electrophilic cyclization to give 2-hydroxy-lepidine, (c) replacement... 

Although the general reaction route of the Ainley and King synthesis is generally followed, each step has been modified in same way to produce large quantities of quinine. Some of the modifications are the removal of chlorine by zinc and acetic acid to form lepidine and the formation of quininic acid in acetone during the oxidation. ... 

Synthesis of Quinaldines and Lepidines by a Doebner-Miller Reaction Under Thermal and Microwave Irradiation Conditions... 

Shivaprasad G, Rajesh R, Perumal PT (2006) Synthesis of quinaldines and lepidines by a Doebner-Miller reaction under thermal and microwave irradiation conditions using phospho-tungstic acid. Tetrahedron Lett 47 1783-1785... 

Electron transfer reactions involving hexabutylditm have also been reported, and these types of reactions have been shown to lead to the alkylation of protonated pyridine derivatives including lepidine (Scheme 3). Similar reactions using tetraalkyltin compounds are also possible, as outlined in the next section of this chapter. 

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