Quinolines conversion into

The synthesis of meconin has been referred to already (p. 201). Cotarnine has been synthesised by Salway from myristicin (I) as a starting-point. This was transformed into jS-3-methoxy-4 5-methylenedioxy-phenylpropionic acid (II), the amide of which was converted by Hofmann s reaction into )S-3-methoxy-4 5-methylenedioxyphenylethylamine, and the phenylacetyl derivative (HI) of this condensed, by heating it in xylene solution with phosphoric oxide, giving rise to the two possible dihydroiso-quinoline derivatives. The first of these substances, 8-methoxy-6 7-methylenedipxy-1-benzyl-3 4-dihydroiioquinoline (IV), on conversion into the methochloride and reduction with tin and hydrochloric acid, gave... 

These results indicate that quinine and quinidine differ in structure from cinchonine and cinehonidine in containing a methoxyl group in position 6 in a quinoline nucleus. The identity of the other oxidation products, meroquinenine, cincboloiponic and loiponic acids, in all foiu" cases indicates that the second half of the molecule has the same structure in all four alkaloids. Further, this second half must be joined to the quinoline nucleus at position 4 by a group capable of conversion into carboxyl. 

The quinaldine can also be separated from the crude mixture of bases by conversion into the zinc chloride double salt in the manner described in the case of quinoline. This furnishes a somewhat smaller yield of a purer preparation. 

Irradiation of 2-(2-hydroxyethyl)quinoline resulted in 73% conversion into 2-methylquinoline and formaldehyde. In this case the abstraction of H from OH must occur if the reaction is to be similarly described [Eq. (27)]. 

Further examples of ANRORC reactions are the conversions of quinoline (896) into quinazoline (897) and of pyrimidine (898) into triazine (899). 

A -oxide similarly yields 1-cyanoisoquinoline, in 81% yield. ° Tetrahydro-quinoline is activated to deprotonation at the 2-position by conversion into the formamidine derivative (66). Subsequent reaction of the anion with electrophiles leads to 2-substituted derivatives (see also p. 311) (Scheme 42), ... 

Azaserine, a glutamine antagonist," is known to inhibit the NAD synthetase reaction in which nicotinic acid adenine dinucleotide is converted into NAD with glutamine or ammonia as the nitrogen donor. ° When azaserine or azaleucine was fed to Ricinus communis plants followed by [6- C]quinolinic acid, a marked decrease in incorporation of radioactivity into ricinine was observed with azaleucine, less so with azaserine." Both azaserine and azaleucine were found also to inhibit the incorporation of [6- " C]quinolinic acid into pyridine nucleotide cycle intermediates [in the case of azaserine the conversion of nicotinic acid dinucleotide into nicotinamide adenine dinucleotide (NAD ) was apparently inhibited]. 

The mechanism of nucleophilic reduction involves the formation of an intermediate containing exocyclic C=CF2 double bond and its further conversion into —CH3 group through the sequential hydrogenation/HF elimination processe. Interestingly, 3-CF3 quinoline reacts with LiAlFLj with the formation of dihydroquinoline 105 and the product of similar structure 106 was isolated in the reaction of 3-CF3-pyridine with butyl lithium. ... 

A suspension of 2,6-di-p-bromophenyl-4-phenylpyrylium tetrachloroferrate in 96%-ethanol refluxed 14 hrs. with excess phenylhydrazine -> pyrazolo[2,3-a]-quinoline deriv. Y 60%. - Phenylhydrazine acts also as catalyst. Other agents such as hydrazine, hydroxylamine, or triethylamine were ineffective. F. e. and reactions of the products such as conversion into N-aminocarbostyrils, s. C. L. Pedersen and O. Buchardt, Acta Chem. Scand. 24, 834 (1970). 

Dewar published many papers on spectroscopy, partly with G. D. Liveing in Cambridge. Besides his work on pyridine (see p. 564) he published on the oxidation of phenol and the structure of unsaturated hydrocarbons, derivatives of meconic acid, cystine (with Gamgee), the conversion of quinoline (leucoline) into aniline, the quinoline series, the formation of hydrocyanic acid in the carbon arc burning in air, and the reduction of invett sugar by sodium amalgam, in which he found that both glucose and fructose are reduced, not fructose alone as Linnemann supposed (see p. 820). 

The idea that the opium alkaloid morphine is a modified benzyliso-quinoline provided the key to the structure 6.152) for the alkaloid twisting of the benzylisoquinoline skeleton into that shown for reticuline (6.127) in (6.148) illustrates this relationship and suggests a possible biogenesis. This was later proved correct in the course of a study which is one of the classics of alkaloid biosynthesis. In the first experiments ever to be carried out with complex plant-alkaloid precursors, [1- C]- and [S- Cj-norlaudanosoline [as (6.123) were fed to opium poppies [99, 100]. They were found to label morphine (6.152), codeine (6.153) and thebaine (6.151) specifically, thus establishing that these alkaloids are indeed benzylisoquinoline derivatives. The key intermediate [101] proved to be reticuline (6.148). Both (R) and (5)-isomers were utilized, the latter by way of (6.155) [101, 102] which allowed its conversion into (i )-reticuline (6.148), the correct intermediate, with the same configuration as the three opium alkaloids [as (6.151). ... 

Condensation of an aniline with a dione with loss of water provides enamine 16. Ketone protonation and cyclization forms 18 followed by loss of water provides quinoline 4. Some have suggested the formation of dication 19 as a requirement to cyclization. Cyclization of 19 to 20 and subsequent conversion to quinoline 4 requires loss of water and acid. Another rendering of the mechanism takes into account participation of an electron-donating group (EDG), which stabilizes intermediate 21. 

These effects are not entirely understood because cyclizations forming 5,8-dimethyl quinolines are not problematic as shown below by the conversion of 46 into 47. 

Analogous to the selectivity observed for the conversion of 48 into 50, pyridyl 51 formed enamine 52 which underwent cyclization to give 4-pyridyl-substituted quinoline 53. Again, imine formation first occurs on the less hindered ketone and subsequent cyclization on the more reactive carbonyl occurred in high yield. ... 

The Meth-Cohn quinoline synthesis involves the conversion of acylanilides 1 into 2-chloro-3-substituted quinolines 2 by the action of Vilsmeier s reagent in warmed phosphorus oxychloride (POCI3) as solvent. ... 

In the Meth-Cohn quinoline synthesis, the acetanilide becomes a nucleophile and provides the framework of the quinoline (nitrogen and the 2,3-carbons) and the 4-carbon is derived from the Vilsmeier reagent. The reaction mechanism involves the initial conversion of an acylanilide 1 into an a-iminochloride 11 by the action of POCI3. The a-chloroenamine tautomer 12 is subsequently C-formylated by the Vilsmeier reagent 13 derived from POCI3 and DMF. In examples where acetanilides 1 (r = H) are employed, a second C-formylation of 14 occurs to afford 15 subsequent cyclisation and... 

Under the conditions of the attempted conversion of the indolenine 17 into the quinoline 18 most of the indolenine was recovered, but there was also formed a small amount of a hydrolysis product, o-acetamido-jS-chloro-a-methylstyrene (22), obtainable in good yield with aqueous ethanolic potassium hydroxide. By analogy with a similar sequence of reactions in the carbocyclic series the hydrolysis product 22 might possibly undergo acid-catalyzed cyclodehydration to the quinoline... 

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