Pyrrole chemistry. XXVIII. Substitution reactions of 1-(phenylsulfonyl)pyrrole and some derivatives

Anderson, Hugh J.; Loader, C. E.; Xu, Ru Xun; Le, Nghia; Gogan, Niall J.; McDonald, Robert; Edwards, Louise

doi:10.1139/v85-149

Cited by 107 publications

(46 citation statements)

References 8 publications

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“…The synthesis of 4,5,6,7-tetrahydroindole derivative 15 (Scheme 2), also proceeding smoothly, followed the same route employed by Huffman and co-workers for the preparation of 1-pentyl-3-(1-naphtoyl)pyrrole (7a). 13 Thus, 12 23 was regioselectively acylated, 24 deprotected by alkaline treatment, and eventually alkylated in standard conditions to give 15. Compound 17 was obtained from 2,5-dimethyl-1-pentylpyrrole 25 (16), prepared by the already mentioned N-alkylation procedure, and g-butyrolactone in polyphosphoric acid, according to the method of Moussavi et al 26 (Scheme 3).…”

Section: Resultsmentioning

confidence: 99%

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Synthesis and structure–activity relationships of a series of pyrrole cannabinoid receptor agonists

Tarzia

Duranti

Tontini

et al. 2003

Bioorganic & Medicinal Chemistry

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Abstract-We designed and synthesized a series of pyrrole derivatives with the aim of investigating the structure-activity relationship (SAR) for the binding of non-classical agonists to CB 1 and CB 2 cannabinoid receptors. Superposition of two pyrrole-containing cannabinoid agonists, JWH-007 and JWH-161, allowed us to identify positions 1, 3 and 4 of the pyrrole nucleus as amenable to additional investigation. We prepared the 1-alkyl-2,5-dimethyl-3,4-substituted pyrroles 10a-e, 11a-d, 17, 21, 25 and the tetrahydroindole 15, and evaluated their ability to bind to and activate cannabinoid receptors. Noteworthy in this set of compounds are the 4-bromopyrrole 11a, which has an affinity for CB 1 and CB 2 receptors comparable to that of well-characterized heterocyclic cannabimimetics such as Win-55,212-2; the amide 25, which, although possessing a moderate affinity for cannabinoid receptors, demonstrates that the 3-naphthoyl group, commonly present in indole and pyrrole cannabimimetics, can be substituted by alternative moieties; and compounds 10d, 11d, showing CB 1 partial agonist properties. #

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Section: Resultsmentioning

confidence: 99%

“…The organic layer was dried (Na 2 SO 4 ), and concentrated. Purification of the residue by column chromatography (cyclohexane/EtOAc 8:2) afforded pure 1,3-dicyclohexyl-2-(2,5-dimethyl-1-pentyl-1H-pyrrole-3-carbonyl)isourea (24) …”

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confidence: 99%

Synthesis and structure–activity relationships of a series of pyrrole cannabinoid receptor agonists

Tarzia

Duranti

Tontini

et al. 2003

Bioorganic & Medicinal Chemistry

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“…8,11 In contrast, nitration (HNO 3 −Ac 2 O) proceeds almost exclusively in the 3-position. 10 As was established recently, the same orientation applies to the sulfonation of unsubstituted pyrrole and N-methylpyrrole with pyridine sulfotrioxide.…”

Section: Methodsmentioning

confidence: 99%

“…The effect of the N-phenylsulfonyl substituent was studied in detail. This substituent was simultaneously offered by two groups of researchers [8][9][10][11] as an original protecting group that owing to its electron-withdrawing effect deactivates preferably the α-position and allows one to obtain β-substituted derivatives, the PhSO 2 group being readily removed on alkaline hydrolysis. 10 The effect of the PhSO 2 group was studied in most detail for Friedel−Crafts acylation.…”

Section: Issn 1551-7012mentioning

confidence: 99%

“…10 The effect of the PhSO 2 group was studied in most detail for Friedel−Crafts acylation. [8][9][10][11][12][13][14][15] The role of the nature of the reagent reveals itself most distinctly in the fact that in the presence of aluminum chloride the 3-acylsubstituted derivatives are obtained, while reaction in the presence of boron trifluoride etherate gives the 2-isomers 10 (Scheme 2).…”

Section: Issn 1551-7012mentioning

confidence: 99%

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Positional selectivity in reactions of pyrrole and its N-substituted derivatives with electrophiles

Беленький¹,

Kim²,

Suslov³

et al. 2003

Arkivoc

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Experimental data on the positional selectivity (α:β-ratios) in reactions of N-substituted pyrroles with electrophiles have been considered. Based on the results of quantum chemical calculations of model N-R-pyrroles (R=H, Me, Et, i-Pr, t-Bu, CH=CH 2 , C≡CH, Ph, PhSO 2 , 4-O 2 NC 6 H 4 ) and their α-or β-protonated σ-complexes, carried out using ab initio methods (RHF/6-31G(d), MP2/6-31G(d)//RHF/6-31G(d)), and within the framework of density functional theory (B3LYP/6-31G(d)), it has been shown that the predominant α-or β-orientation is determined by steric factors and charges on the atoms β-С, α-С, N, and on the substituents at the N atom. We conclude that it is not determined by differences in the relative stabilities of the onium state N + depending on the nature of a substituent at the N atom, or reflecting the role of the heteroatom in the stabilization of σ-complexes formed by β-substitution.

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TheVilsmeier Reaction of Fully Conjugated Carbocycles and Heterocycles

Jones

Stanforth

1996

Organic Reactions

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In 1925 Fischer, Müller, and Vilsmeier published a paper describing the reaction between phosphoryl chloride and N ‐methylacetanilide, giving a number of products, including the quinolinium salt and another salt. The probable course of the reaction was given in a paper by Vilsmeier and Haack in 1927, and they made the important discovery that the reagent obtained from N ‐methylformanilide and phosphoryl chloride, represented as a salt, would react with N,N ‐dimethylaniline, giving 4‐ N,N ‐dimethylaminobenzaldehyde. No 2‐substituted products were observed in this reaction. Other N,N ‐dialkylaniline derivatives, including 3, N,N ‐trimethylaniline and 1‐ N,N ‐dimethylaminonaphthalene were also successfully used as substrates to prepare aromatic aldehyde derivatives. The gradual development of the reagent for synthesis was accompanied by interest in the nature of the reagent. It was discovered that other acid chlorides (e.g., thionyl chloride, carbonyl chloride, and oxalyl chloride) could be used in the reaction and that substituted amides other than formamides gave ketones, although in generally poorer yields. Thionyl chloride frequently gives sulfur‐containing products. The most commonly used amide is dimethylformamide (DMF) and there is now a consensus that the reagent formed from DMF and most acid chlorides, other than phosphoryl chloride, can be represented by the structure given in the chapter, and this is illustrated for the reaction between DMF and carbonyl chloride. The salt is a stable compound and is often isolated before being reacted with a substrate. It seems likely that the most commonly used reagent, that made from DMF and phosphoryl chloride, is an equilibrium mixture of iminium salts. Recent unpublished spectroscopic studies have indicated that in DMF solution there is an equilibrium mixture of iminium compounds. One of the electrophilic chloroiminium salts then reacts with a substrate in an electrophilic substitution process yielding an iminium salt, which is usually hydrolyzed to the aromatic aldehyde. Vinylogous chloroiminium salts can be prepared from the corresponding vinylogous formamide derivatives and these yield, after hydrolysis, α,β‐unsaturated products. This particular reaction is generally limited to more reactive substrates. The formation of carbon–carbon bonds to fully conjugated carbocycles and heterocycles is the subject of this chapter; a subsequent chapter considers carbon–carbon bond‐formation reactions in alkenes (including heterosubstituted alkenes such as enamines and enol ethers), alkynes, and activated methyl and methylene compounds (aldehydes, ketones, carboxylic acid derivatives, and nitriles). It is not surprising that the Vilsmeier reaction has been the subject of many review articles of varying scope and length. With so many excellent reviews dealing with the Vilsmeier reaction, its mechanism, and the structure of the various electrophilic reagents, coverage is restricted to important concepts rather than reiterate all the literature material. A brief description of the mechanism and regiochemistry of the Vilsmeier reaction is presented and this is elaborated with appropriate cases that deal with specific compound types.

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Pyrrole chemistry. XXVIII. Substitution reactions of 1-(phenylsulfonyl)pyrrole and some derivatives

Cited by 107 publications

References 8 publications

Synthesis and structure–activity relationships of a series of pyrrole cannabinoid receptor agonists

Synthesis and structure–activity relationships of a series of pyrrole cannabinoid receptor agonists

Positional selectivity in reactions of pyrrole and its N-substituted derivatives with electrophiles

TheVilsmeier Reaction of Fully Conjugated Carbocycles and Heterocycles

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