Pyrroles reaction with quinolines

Heterocyclic amines are compounds that contain one or more nitrogen atoms as part of a ring. Saturated heterocyclic amines usually have the same chemistry as their open-chain analogs, but unsaturated heterocycles such as pyrrole, imidazole, pyridine, and pyrimidine are aromatic. All four are unusually stable, and all undergo aromatic substitution on reaction with electrophiles. Pyrrole is nonbasic because its nitrogen lone-pair electrons are part of the aromatic it system. Fused-ring heterocycles such as quinoline, isoquinoline, indole, and purine are also commonly found in biological molecules. 

Mono- and dilithio derivatives of p-tosylmethyl isocyanide 297a were shown to display interesting reactions. Reaction of the monoanion with unsaturated esters was shown to give pyrrole derivatives . Dianion 297b was found to add to the carbon-nitrogen double bonds of isoquinoline, quinoline and quinoxaline affording compounds 298, 299 and 300, respectively. In the reactions with pyridine iV-oxide and pyridazine iV-oxide, unstable open-chain products 301 and 302 were obtained . 

The reagent reacts with pyrrole (4) at temperatures below 40° to give N -clhoxy-carbonylpyrrolc-2-thiocarboxamidc (5) in 93% yield. When (5) is heated with quinoline it is converted into 2-thiopyrrole-l,2-dicarboximide (6). Reaction of pyrrlyl-... 

More recently, Lautens has also employed l-(2-iodophenyl)-pyrrole as a bifunctional aryl iodide/acceptor for the synthesis of substituted pyrrolo[l,2]quinolines (Scheme 34)[82], During Catellani s application of the Cassar-Sonogashira reaction to the ort/m-alkylation sequence [70] it was found that alkynes can undergo further carbopalladation reactions with arylpalladium(II) species. It was this reactivity which led Lautens to explore the use of bromoalkylalkynes as species which can undergo an ort/zo-alkylation, followed by a cyclocarbopalladation onto the alkyne,... 

Homologs of pyridine, quinoline, thiophen, and various other heterocycles can be oxidized to carboxylic acids generally without destruction of the hetero ring in the pyrrole series, however, this cannot be done directly but requires intervention of an intermediate (see Fischer et al.A05). More circuitous routes are also sometimes preferable in the quinoline series for instance, in their total synthesis of hydroquinine Rabe et a/.406 obtained the 4-carboxylic acid from 6-methoxy-4-methylquinoline by oxidizing the 4-styryl derivative (obtained by reaction with benzaldehyde) instead of oxidizing the methyl compound directly. Alkyl groups at positions 2 and 4 of pyridine are more easily oxidized than those at position 3. 

Ludwig Elnorr (Munich, 2 December 1859-Jena, 5 June 1921), a pupil of Baeyer, Bunsen, and Emil Fischer, was associate professor in Wurzburg (1888) and professor in Jena (1889). He did much work on pyrazolones (1883-1911) by condensing acetoacedc ester and phenylhydrazine he obtained 3-methyl-i-phenylpyrazolone, which on methylation forms antipyrine. He synthesised quinoline, pyrazole derivatives from jS-diketones or ketonic esters and phenylhydrazine, and pyrrole derivatives, and discovered morpholine. He worked on diacetylsuccinic ester, acetylacetone," and acetoacetic ester, from the point of view of tautomerism, calling them allelotropic mixtures (see p. 816), and ised the colour reaction with ferric chloride in detecting the enol-forms. He woiiced on aminoethyl ether and diaminoethyl ether. ... 

In a similar way, the authors of (Lancelot et al. 1983b) synthesized pyrido[2,3-/j] pyrrolo[l,2-a]quinoxalines 223 and 157b from the hydrohalide of 6-amino-5-(pyrrol-l-yl)quinoline 222. The reactions of the 6-amino derivative 222 with... 

In 1931 Ing pointed out that formula (II) and (III) do not contain methyl or potential methyl groups in j ositions 6 and 8 which they occupy in cytisoline. Further, a partially reduced quinoline ought to oxidise easily to a benzenecarboxylic acid and so far the only simple oxidation, products recorded from cytisine were ammonia, oxalic acid and isovaleric acid. Distillation of cytisine with zinc dust or soda-lime yields pyrrole and pyridine, but no quinoline. On these grounds Ing suggested that cytisine should be formulated without a quinoline nucleus, and that the reactions which indicate the presence of an aromatic nucleus in the alkaloid can be accounted for by an a-pyridone ring. This a-pyridone nucleus can... 

These reactions are related to the formation of pyrroles and quinolines from aminocarbonyl compounds and acetylenes (582,583) and may be contrasted with the formation of pyran derivatives by electrophilic attack on an enamine, followed by addition of an oxygen function to the imonium carbon (584-590). 

The idea that dichlorocarbene is an intermediate in the basic hydrolysis of chloroform is now one hundred years old. It was first suggested by Geuther in 1862 to explain the formation of carbon monoxide, in addition to formate ions, in the reaction of chloroform (and similarly, bromoform) with alkali. At the end of the last century Nef interpreted several well-known reactions involving chloroform and a base in terms of the intermediate formation of dichlorocarbene. These reactions included the ring expansion of pyrroles to pyridines and of indoles to quinolines, as well as the Hofmann carbylamine test for primary amines and the Reimer-Tiemann formylation of phenols. 

Oximes and their derivatives are widely used in organic synthesis. A number of reviews are devoted to the chemistry and biological activity of oximes and their derivatives The synthesis, reactions and biological activity of oximes containing a heterocyclic substituent, e.g. furan and thiophene", indole and isatin, pyridine, pyrrole, quinoline and five-membered heterocycles with two heteroatoms have been reviewed. 

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