Friedel-Crafts Cyclialkylations Research Articles

Friedel–Crafts Chemistry. Part 46. Unprecedented Construction of Tricyclic Pyrazolo[3,4-b]quinolines, -[1,8]naphthyridines, -azepines, -azocines, -pyrido[3,2-g]azocines, and pyrazolo[3,4-b]azonines via Friedel–Crafts Ring Closures

A series of keto-substituted pyrazolo[3,4-b]quinolines, pyrazolo[3,4-b][1,8]naphthyridines, benzo[e]pyrazolo[3,4-b]azepines, benzo[g]pyrazolo[3,4-b]azocines, pyrazolo[3,4-b]pyrido[3,2-g]azocines, and benzo[g]pyrazolo[3,4-b]azonines scaffolds were synthesized via a Friedel–Crafts cyclialkylation approach. The precursor acids were obtained by utilizing the modified Ullman coupling reactions of 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carboxylic acid with different aryl amines followed by ring closures in the presence of AlCl3/CH3NO2 or P2O5 or polyphosphoric acid catalysts. Particular attention is given to the novel structures especially in regard to the promising pharmaceutical and therapeutic values associated with their skeletons.

ChemInform Abstract: Friedel—Crafts Chemistry. Part 39. Unprecedented Facile Route to the Synthesis of Benzo[b][1]benzazepines via Intramolecular Friedel—Crafts Cyclialkylations.

A series of six pharmaceutically promising 5,6-dihydro-11H-benzo[b][1]benzazepine derivatives (1c–h) were cleanly prepared by Friedel–Crafts cyclialkylations of nitrogen-containing alkanols in the presence of AlCl3, 85 % H2SO4 or polyphosphoric acid catalysts. The precursor alkanols (13a–f) were readily prepared by reaction of two synthesized carboxylic acid esters (12a, b) with different Grignard reagents. Also, two dibenzo[b,f]azepinones (15a, b) were prepared by Friedel–Crafts cycliacylation and reduced to the corresponding 5,6-dihydro-11H-benzo[b][1]benzazepines (1a, b). Overall, this approach allows easy and efficient access to polytricyclic amines from easily synthesized alkanols or cycloketones. A plausible carbocation mechanism is proposed to account for the results.

Modern Friedel-Crafts Chemistry. Part 38. Facile Synthesis of Acenaphthenes via Direct and Rearranged Intramolecular Friedel-Crafts Cyclialkylations of Intermediate Carbinols

A novel one-pot synthesis of six di-, tri-, and tetra-substituted acenaphthenes 18a-f via direct and/or rearranged Friedel-Crafts cyclialkylations of seven novel carbinols 1a-g is described. The methodology involves treatment of alkanols 1a-g in the presence of both Brønsted (PPA, H2SO4) and Lewis (AlCl3/CH3NO2) acid catalysts. The method offers several advantages such as high yields, high selectivities, and easily accessible starting materials. A plausible mechanism for this type of Friedel-Crafts cyclialkylation is proposed.

Friedel–Crafts Chemistry. Part 39. Unprecedented Facile Route to the Synthesis of Benzo[b][1]benzazepines via Intramolecular Friedel–Crafts Cyclialkylations

A series of six pharmaceutically promising 5,6-dihydro-11H-benzo[b][1]benzazepine derivatives (1c–h) were cleanly prepared by Friedel–Crafts cyclialkylations of nitrogen-containing alkanols in the presence of AlCl3, 85 % H2SO4 or polyphosphoric acid catalysts. The precursor alkanols (13a–f) were readily prepared by reaction of two synthesized carboxylic acid esters (12a, b) with different Grignard reagents. Also, two dibenzo[b,f]azepinones (15a, b) were prepared by Friedel–Crafts cycliacylation and reduced to the corresponding 5,6-dihydro-11H-benzo[b][1]benzazepines (1a, b). Overall, this approach allows easy and efficient access to polytricyclic amines from easily synthesized alkanols or cycloketones. A plausible carbocation mechanism is proposed to account for the results.

Modern Friedel-Crafts chemistry: Part 36. Facile synthesis of some new pyrido[3,2,1-jk]carbazoles via Friedel-Crafts cyclialkylations

An efficient methodology for the synthesis of novel substituted pyrido[3,2,1-jk]carbazole via Friedel-Crafts cyclialkylations is reported. The methodology was realized by three-step protocol involved the addition of carbazole to 3-methylcrotononitrile. The resulted nitrile was hydrolyzed to desired ester, followed by addition of Grignard reagents to afford tertiary alcohols and/or reacted directly with different Grignard reagent to form the desired ketones. The later ketones were converted to both secondary and tertiary alcohols by reduction with LAH and addition of Grignard reagents respectively. These carbinols were cyclialkylated under Friedel-Crafts conditions catalyzed by AlCl3/CH3NO2, PTSA and PPA to give tri-and tetrasubstituted pyrido[3,2,1-jk]carbazole.

Modern Friedel-Crafts chemistry. Part 35. New synthetic approach to substituted indolo[2,1-a][2]benzazepines and indolo[2,1-a]isoquinolines via Friedel-Crafts cyclialkylations

Facile procedures for the construction of fused indole-containing heteropolycycles 1a-f and 2a-c have been developed. The methodology involves Friedel-Crafts cyclialkylations of heteoraryl alkanols in the presence of both Bronsted (PPA) and Lewis (AlCl3/CH3NO2) acid catalysts. The starting alkanols 6a-f and 12a-c were smoothly obtained both by reactions of the corresponding carboxylic acid esters and the corresponding ketones with Grignard reagents. Overall, this approach allows for easy and efficient access to polycyclic indoles from easily synthesized precursors.

Total Synthesis of (±)-Komaroviquinone

(±)-Komaroviquinone (1) was synthesized from 3,4,5-trimethoxybenzoic acid in twenty-two steps. The key transformations in this synthesis are: (1) the construction of the cycloheptane ring via a Friedel-Crafts cyclialkylation; (2) a regiospecific benzylic oxidation; (3) a conformationally controlled introduction of the C(10) hydroxyl group and (4) intramolecular hemi-acetal formation.

A New Synthesis of Isochromans and Phtalans

Abstract A short and efficient synthesis of isochromans and phtalans has been devised. This synthesis involves the intramolecular Friedel-Crafts cyclialkylation of oxonium species generated by reaction of MEM ethers with Lewis acids.

Friedel-Crafts cyclialkylations of some epoxides. 3. Cyclizations of tertiary and meta-substituted arylalkyl epoxides

Friedel-Crafts cyclialkylations of some epoxides. 3. Cyclizations of tertiary and meta-substituted arylalkyl epoxides

Friedel-Crafts cyclialkylations of some epoxides. 2. Stereospecificity, substituent, product, and kinetic studies

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTFriedel-Crafts cyclialkylations of some epoxides. 2. Stereospecificity, substituent, product, and kinetic studiesStephen K. Taylor, Mark E. Davisson, B. Rolf Hissom Jr., Sandra L. Brown, Holle A. Pristach, Scott B. Schramm, and Suzanne M. HarveyCite this: J. Org. Chem. 1987, 52, 3, 425–429Publication Date (Print):February 1, 1987Publication History Published online1 May 2002Published inissue 1 February 1987https://doi.org/10.1021/jo00379a021RIGHTS & PERMISSIONSArticle Views425Altmetric-Citations28LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (643 KB) Get e-Alerts Get e-Alerts

Friedel-Crafts cyclialkylations of some epoxides

On etudie les reactions de cyclialkylation d'une serie d'arylalkylepoxydes conduisant a des derives du tetrahydronaphtalenemethanol-1, du tetrahydronaphtol-2 et du benzocycloheptene methanol-5

Ortho Diquaternary Aromatic Compounds. IV. Acid-catalyzed Rearrangements of Polyalkyltetralones and Related Ketones

The ketones 1,1,4,4-tetramethyl-2-tetralone (1a), 1,1,4,4,7-pentamethyl-2-tetralone (1b), and 1,1,4,4,6-pentamethyl-2-tetralone (1c) undergo rearrangement on heating with aluminum chloride or ferric chloride in tetrachloroethane or nitromethane into mixtures of their respective isomeric ketones, 1-acetyl-1,3,3-trimethylindane (2a) and 2,2,4,4-tetramethyl-1-tetralone (3a) from 1a, 1-acetyl-1,3,3,6-tetramethylindane (2b) and 2,2,4,4,7-pentamethyl-1-tetralone (3b) from 1b, and 1-acetyl-1,3,3,5-tetramethylindane (2c) and 2,2,4,4,6-pentamethyl-1-tetralone (3c) from 1c. A quantitative study using g.l.c. of the distribution of the ketones with time shows that the sequence of the rearrangement is: [Formula: see text]. A methyl group homologously para to the carbonyl (1c) accelerates the rearrangement. The same kind of rearrangement takes place during Friedel–Crafts cyclialkylation with 2,2,5,5-tetramethyltetrahydrofuranone. A unifying reaction mechanism is postulated to account for the rearrangements. This mechanism also accounts for the rearrangement and fragmentation products from treatment of 1,1,4,4-tetramethyl-2,3-dioxotetralin (9) with aluminum chloride or sulphuric–acetic acids. The products from 9 include 1-acetyl-1,3,3-trimethyl-2-indanone, 1,1,3-trimethyl-2-indanone, and, from the aluminum chloride – catalyzed rearrangement, 5(or 6)-acetyl-1,1,3-trimethyl-2-indanone.

Friedel-Crafts cyclialkylations of certain mono- and diphenyl-substituted alcohols and alkyl chlorides

Friedel-Crafts cyclialkylations of certain mono- and diphenyl-substituted alcohols and alkyl chlorides

Experiments directed toward the total synthesis of terpenes. XVII. Development of methods for the synthesis of pentacyclic triterpenes based on a mechanistic interpretation of the stereochemical outcome of the Friedel-Crafts cyclialkylation reaction

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExperiments directed toward the total synthesis of terpenes. XVII. Development of methods for the synthesis of pentacyclic triterpenes based on a mechanistic interpretation of the stereochemical outcome of the Friedel-Crafts cyclialkylation reactionRobert E. Ireland, Steven W. Baldwin, and Steven C. WelchCite this: J. Am. Chem. Soc. 1972, 94, 6, 2056–2066Publication Date (Print):March 1, 1972Publication History Published online1 May 2002Published inissue 1 March 1972https://doi.org/10.1021/ja00761a044RIGHTS & PERMISSIONSArticle Views243Altmetric-Citations25LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts Get e-Alerts

New Friedel-Crafts chemistry. XXV. Friedel-Crafts cyclialkylations and bicyclialkylations with diphenylalkyl chlorides

New Friedel-Crafts chemistry. XXV. Friedel-Crafts cyclialkylations and bicyclialkylations with diphenylalkyl chlorides

Friedel–Crafts rearrangements. III. Deuterium tracer studies of the mechanism of cyclialkylation of phenylalkyl chlorides

A series of dideuterated primary phenylalkyl chlorides 1-chloro-3-phenylpropane-2,2-d2 (4), 1-chloro-3-phenylpropane-1,1-d2 (9), 1-chloro-4-phenylbutane-2,2-d2 (8), 1-chloro-5-phenylpentane-4,4-d2 (5), 1-chloro-5-phenylpentane-3,3-d2 (6), and 1-chloro-5-phenylpentane-2,2-d2 (7) were synthesized by alkylations of malonic ester with phenylalkyl chlorides. Deuterium was introduced by exchange of the sodium salt of the alkylated malonic ester with D2O, followed by hydrolysis and decarboxylation. The resulting acids were reduced by hydride to primary alcohols and these were converted to the dideuterated primary chlorides by decomposition of the intermediate chlorosulfite esters. Nuclear magnetic resonance (n.m.r.) spectra confirmed the position of the deuterium in the chlorides. Friedel–Crafts cyclialkylation of the deuterated phenylpentyl chlorides yielded labelled 1-methyltetralins in which the label was located by n.m.r. and mass spectroscopy. The results demonstrated that rearrangement precedes cyclialkylation of 1-chloro-5-phenylpentane. Extensive deuterium scrambling between C-1, C-2, and C-3 accompanied the cyclialkylation of 5 but not that of 8. Reaction mechanisms are suggested to account for these results.

Friedel–Crafts rearrangements. IV. Cyclialkylations and hydride transfers on phenylalkyl chlorides

A number of phenylalkyl chlorides were synthesized for a comparative study of Friedel–Crafts cyclialkylations and competing reactions involving hydride exchange. The synthetic work showed that phenylbutyl alcohols, especially a tertiary alcohol, may cyclize directly with chlorinating agents to yield tetralins. Cyclialkylation products from phenylpentyl chloride include 1-methyltetralin (4), n-pentylbenzene, 1-methyl-3,4-dihydronaphthalene, and methylnaphthalene. A reaction sequence is given involving dealkylation of 4 and hydride transfers. Phenylbutyl chloride yielded tetralin, n-butylbenzene, and naphthalene. 1-Chloro-4-methyl-4-phenylpentane yielded 1,1-dimethyltetralin (10), 2-methyl-5-phenylpentane (11), and a small amount of 2-methyl-2-phenylpentane (12). Hydrocarbon 11 formed from 10 after cyclialkylation, while 12 formed by hydride transfer preceding cyclization. Phenylpropyl chloride yielded mainly a hydride transfer product (propylbenzene) and not indane. Treatment of this chloride containing deuterium labels at C-1 and C-2 showed that the hydride ion rearranges from the carbon adjacent to the halogen. 1-Chloro-3-methyl-3-phenylbutane yielded a complex mixture including t-pentylbenzene, 2-phenyl-3-methylbutane, and products of higher molecular weight.

FRIEDEL–CRAFTS REARRANGEMENTS: II. REARRANGEMENTS DURING CYCLIALKYLATION OF ε-ARYL-SUBSTITUTED COMPOUNDS

Friedel–Crafts cyclialkylation of aromatics such as 1,1,4,4-tetramethyltetralin with 2,6-dichloro-2,6-dimethylheptane does not yield a benzsuberane as previously reported. Several 5-phenyl-substituted chlorides, alcohols, and olefins were synthesized for cyclialkylation studies. These included 2-chloro-2,6-dimethyl-6-phenylheptane (Xa), 3-chloro-3,7-dimethyl-7-phenyloctane (Xb), 2,6-dimethyl-6-phenyl-2-heptanol, 2,6-dimethyl-6-phenyl-2-hepten-4-one (XX), 2-chloro-6-methyl-6-phenylheptane, and 1-chloro-5-phenylpentane (XXIV). Cyclialkylation of Xa (and the corresponding alcohol), Xb, 2-chloro-6-methyl-6-phenyl-heptane, and XXIV produced alkyltetralins instead of benzsuberanes. Evidence is presented and discussed which indicates that the alkyltetralins form by rearrangements in the side chains of the aryl-substituted systems. The alternative mechanism involving rearrangement of a benzsuberane intermediate via a phenonium ion mechanism was unequivocally ruled out in at least one case—the cyclization of Xb. Nuclear magnetic resonance evidence is presented for the structural assignments.