Fischer polyphosphoric acid

Reaction of phenyldiazonium chloride with 66 provides 6-phenylhydrazono derivative 72. Fischer indolization reaction of 72 in polyphosphoric acid gives pentacyclic 3-azarutecarpine derivatives 73 (Equation 3) <1996T7789>. 

FISCHER INDOLE SYNTHESIS Phosphorus trichloride. Polyphosphoric acid. 

A variety of both protic and Lewis acids have been used to effect Fischer cyclizations. Hydrochloric acid or sulfuric acid in aqueous, alcohol or acetic acid solution are frequently used. Polyphosphoric acid and BF3 in acetic acid have also been employed[10]. Zinc chloride is the most frequently used of the common Lewis acids. This choice is supported by comparative studies with FeCI3, AICI3, CoCI2 and NiCl2, which found ZnCl2 to be the most effective catalyst[l 1]. Zinc chloride can be used either as a solid mixture with the hydrazone reactant or in ethanol or acetic acid solution[12]. 

The synthesis of indoles by the Fischer method has been the subject of a review, where phosphorus trichloride and polyphosphoric acid were used as cyclizing agents [6], Although the first publication on the synthesis of phosphorus-containing indoles appeared in 1930 [7], reviews on this subject are few. The treatment of the subject in [8] was fragmentary, while the review [9] covered the literature up to 1975. It is also possible to mention [10], which was devoted to the phosphorylation of pyrrole and its carbonyl derivatives. 

The synthesis of dialkyl 3-aryl-2-indolylphosphonates 171 by the Fischer indole synthesis by the cycloaddition of arylhydrazines with a-ketophosphonates in polyphosphoric acid or under the influence of zinc chloride was described [183] ... 

The Fischer indole synthesis itself is catalysed in this case by polyphosphoric acid (PPA), a sticky gum based on phosphoric acid (H3PO4) but dehydrated so that it contains some oligomers. It is often used as a catalyst in organic reactions and residues are easily removed in water. 

He and his students developed C-alkylation with quaternary ammonium salts and nucleophilic displacements on such salts, including the stereochemistry. His name is immediately associated with important innovations in the use of polyphosphoric acid for inter- and intramolecular condensations, cyclizations, and functional conversions in organic chemistry. He pioneered the use of boron trifluoride as an efficient catalyst in the Fischer indole synthesis and discovered new reactions of anils, including Diels-Alder reactions. He and his students delineated the requirements for disproportionation of tertiary amines. He developed the synthesis and chemistry of arylboranic acids. One of his fundamental ideas was for the incorporation of sufficient boron into organ-specific drugs that they could then be... 

Efforts to synthesize apoharmine (1, R = Me) by Fischer cyclization of ethyl pyruvate 2-methyl-3-pyridylhydrazone failed, whereas its cyclohexanone hydrazone gave tetrahydroharman (27, R = Me) in 11 % yield on heating with zinc chloride. This yield seems quite low compared to the 94 % yield of a 2 1 mixture of tetrahydro-S-carboline (28) and tetrahydro-j8-carboline (27, R = H), respectively, obtained from cyclohexanone 3-pyridylhydrazone under similar conditions. Okuda and Robison were able to cyclize cyclohexanone 2-pyridyl-hydrazone to 5,6,7,8-tetrahydro-a-carboline in 53 %yield on heating in polyphosphoric acid, but the acetaldehyde, acetone, and pyruvic acid... 

Fischer ineiole synthesis Ethylene glycol. Polyphosphate ester. Polyphosphoric acid. Zinc chloride. 

Appreciable formation of the linear 2-benzyl-3-/f-indole by the Fischer synthesis with 1-phenyl-2-propanone was only observed with polyphosphoric acid and not at all with zeolite beta, although this product resembles, in bulkiness, 2-benzyl-3-methylindole, the linear indole isomer obtained from 1-phenyl-2-buta-none. If the production of the linear isomer depended solely on suppression of the formation of the bulky product, then the trends in the selectivities for 1-phenyl-... 

It is worth pointing out that reaction of the phenylhydrazone of 402 in polyphosphoric acid did not give a compound in the Aspidosperma series but one derived by Fischer cyclization at the other a-position. Lithium aluminum hydride reduction then gave the indole derivative 404. 

A -Arylhydrazones, derived from enolizable aldehydes or ketones 30, are converted into indoles 31 under Lewis (ZnCl2, BF3) or Bronsted acid (H2SO4, polyphosphoric acid, CH3COOH, HCl in ethanol) catalysis with loss of ammonia Fischer synthesis, E. Fischer 1883) ... 

An important type of aromatic Claisen rearrangement occurs in the Fischer indole synthesis. " The Fischer indole synthesis involves the condensation of an arylhydrazine with an aldehyde or ketone to give an arylhydrazone, which, in the presence of a catalyst undergoes rearrangement and elimination of ammonia to give the indole ring. One of many different protic or Lewis acid catalysts can be used. For example, Woodward s synthesis of strychnine commenced with the condensation of the ketone 303 and phenylhydrazine in the presence of polyphosphoric acid to give the indole 304 (3.194). 

According Fischer reaction from 1-acetyladamantane and phenyl hydrazine 2-(l-adamantyl)indole(I) was obtained in polyphosphoric acid. As a result of its aminomethylation according Mamiich ieaction[7] w as obtained an analog of indole alkaloid gramine - 2-(l-adamantyl)-3- dimethylaminomethylindole(III). Reaction was carried out at the condition similar to indole [8]. As a result of interaction between indole-2-carboxylic acid chloride (II) [4] and 1-adamantyl-amine in absolute benzene was obtained 2-(l-adamantyl)amino-carbonylindole(IV) with 31% yield. Compound III was transformed into water-soluble salt - methylsulphate-V, methyliodide VI and hydrochloride-VII. 

Friedel-Crafts reactions, the Fischer indole synthesis, the Beckmann rearrangement, and other dehydrations an alternative to polyphosphoric acid )... 

Woodward s strychnine synthesis commences with a Fischer indole synthesis using phenylhydrazine (24) and acetoveratrone (25) as starting materials (see Scheme 2). In the presence of polyphosphor-ic acid, intermediates 24 and 25 combine to afford 2-veratrylindole (23) through the reaction processes illustrated in Scheme 2. With its a position suitably masked, 2-veratrylindole (23) reacts smoothly at the ft position with the Schiff base derived from the action of dimethylamine on formaldehyde to give intermediate 22 in 92% yield. TV-Methylation of the dimethylamino substituent in 22 with methyl iodide, followed by exposure of the resultant quaternary ammonium iodide to sodium cyanide in DMF, provides nitrile 26 in an overall yield of 97%. Condensation of 2-veratryl-tryptamine (20), the product of a lithium aluminum hydride reduction of nitrile 26, with ethyl glyoxylate (21) furnishes Schiff base 19 in a yield of 92%. 

Fischer indole synthesis. The synthesis of a 2-substituted indole by the method of Fischer " can be interpreted as shown in the formulation. An Organic Syntheses preparation of 2-phenylindole specified heating acetone phenylhydrazone with five times its weight of zinc chloride al 170° and adding 4 parts of sand to prevent solidification on cooling (yield of 2-phenyllndole 72-HO%). Chapman el /. studied various cyclizing agents (coped, hydrochloric acid, dry HCI, BFn. polyphosphoric... 

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