Intramolecular Ipso Substitution Research Articles

Intermolecular Ipso Aromatic Nucleophilic Substitution of Electron‐Deficient Aryl Sulfonyl Chlorides

AbstractA mild and efficient approach is described for generating substitution products of electron‐deficient benzenesulfonyl chlorides via intermolecular ipso aromatic nucleophilic substitution reaction. Various amines and thiols effectively undergo a transition‐metal‐free coupling process, leading to diaryl or arylalkyl amines and thioethers with the formation of C─N and C─S bonds. The regioselective attack of N‐nucleophiles produces sulfonamides in the absence of a base. This reaction generates the Smiles rearrangement products. However, a series of mechanistic investigations point toward the intermolecular pathway in contrast to the intramolecular ipso substitution, known as Smiles rearrangement.

Brønsted acid- and Ni(II)-catalyzed C-H oxidation/rearrangement of cyclotriveratrylenes (CTVs) to cyclic and acyclic quinones as potential anti-cancer agents.

This paper describes a simple and practical protocol for the direct synthesis of acyclic and cyclic quinone derivatives via an acid-promoted nickel(II)-catalyzed inner rim C-H oxidation of cyclotriveratrylene (CTV) and its analogues. The cyclic quinone derivatives resulted from trimethoxy-cyclotriveratrylene (TCTV) through C-C bond formation via intramolecular ipso substitution followed by subsequent anionic rearrangement containing stereo-vicinal quaternary centers. The DFT calculations strongly support the experimental findings and reveal the role of Brønsted acids in the C-H bond activation of CTV. All the newly synthesized compounds were screened for their in vitro anti-cancer activity using colorimetric SRB assay analysis. Among them, compounds 3a, 3d, 3h, 4a, 4b, 4c and 4e exhibited moderate anticancer activity against A549, HCT-116, PC-3, MDA-MB-231, HEK-293 and SW620 human cancer cell lines.

Pd-catalysed intramolecular transformations of indolylbenzenesulfonamides: ortho-sulfonamido-bi(hetero)aryls via C2-arylation and polycyclic sultams via C3 arylation

Palladium-catalysed and base-dependent intra-molecular ipso-substitution and cyclisation strategies involving N-indolyl-substituted aryl-sulfonamides for the rapid construction of 2-aryl indole and indole-fused six-membered sultams are described. The Pd(OAc)2/Ph3P/Et3N combination delivers indolyl C2 arylated motifs via C(2)-N bond cleavage followed by C-C bond formation. In sharp contrast to this, the Pd(OAc)2/Ph3P/K2CO3 combination induced intramolecular-Heck cross-coupling affords polycyclic sultams exclusively. Thus, this strategy is completely additive-dependent. It also shows a broad substrate scope and delivers the corresponding products in good to high yields.

Thermally Induced Cyclization of Electron-Rich N-Arylthiobenzamides to Benzothiazoles

Heating N-(2-methoxyphenyl)benzenecarbothioamides in refluxing nitrobenzene for 24 hours gives the corresponding benzothiazoles with intramolecular ipso substitution of the ortho-methoxy­ substituent. The thermal cyclization of various other N-arylthiobenzamides is also explored.

セシウムエノラートの分子内 ipso 置換を経由する5, 4'-二置換型フラボン類の効率的合成

セシウムエノラートの分子内 ipso 置換を経由する5, 4'-二置換型フラボン類の効率的合成

An Effective Synthesis of 5,4'-Disubstituted Flavones via a Cesium Enolate Assisted Intramolecular ipso-Substitution Reaction

A variety of 5,4'-disubstituted flavones, which are anticipated to be androgen receptor antagonists to treat diseases mediated by the androgen receptor, were synthesized. It was found that an intramolecular ipso-substitution reaction via cesium enolate using 2-fluoro-6-hydroxyacetophenone and various benzoyl chlorides was effective in the preparation of 5-hydroxy-4'-alkylflavones.

Solid phase synthesis of 3-(5-arylpyridin-2-yl)-4-hydroxycoumarins

A solid phase strategy has been developed for the synthesis of 3-(5-arylpyridin-2-yl)-4-hydroxycoumarins. The key transformation is an intramolecular ipso substitution reaction which forms the coumarin heterocycle and culminates with cleavage of product from the polymer support. The pyridine moiety at C3 can be further modified with Suzuki coupling. A sample library with two diversity elements has been synthesized to demonstrate this ipso substation-based cyclo-elimination strategy.

Synthesis and Thermal Transformations of 5‐Nitropyrimidin‐4‐yl Dialkyldithiocarbamates.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and thermal transformations of 5-nitropyrimidin-4-yl dialkyldithiocarbamates

On heating, 5-nitropyrimidin-4-yl dialkyldithiocarbamates undergo two types of transformations. One type of these transformations involves intramolecular ipso-substitution of the nitro group to form bis(4-dialkylcarbamoylthiopyrimidin-5-yl) disulfides, whereas another type of transformations involves elimination of carbon disulfide to give 4,6-diamino-5-nitropyrimidine derivatives. The reaction pathway is controlled by the steric effect of the substituent at position 6 of the pyrimidine ring.

Intramolecular alkene Friedel–Crafts cyclization of 1-allyl-1- N-( ortho-alkylphenylamino)cyclohexanes. A useful route to alkyl substituted dihydrospiro[(1 H)quinoline-2,1 ′-cyclohexanes]. Unprecedented ipso-substitution of alkyl groups

An unprecedented intramolecular Friedel–Crafts ipso-alkylation at the ortho-alkyl group of the N-arylamino moiety of 1-allyl-1- N-arylaminocycloalkanes to give alkyl substituted dihydrospiro[(1 H) quinoline-2,1 ′-cycloalkanes] is reported. Unexpected results were explained in the context of intramolecular ipso-substitution of alkyl groups and their 1,2-rearrangement. A plausible mechanism for this type of Friedel–Crafts alkylation by an alkene moiety promoted by a Brönsted acid (H 2SO 4) is proposed.

Radical Cyclization by Ipso Substitution of the Methoxy Group: Considerable Effect of HMPA on Samarium‐Mediated Cyclization.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Radical cyclization by ipso substitution of the methoxy group: considerable effect of HMPA on samarium-mediated cyclization.

Alkyl radicals generated by treatment of thiocarbamates of conformationally favorable 3-alkyl-3-arylpropan-1-ols with tris(trimethylsilyl)silane and AIBN efficiently undergo intramolecular ipso substitution of the methoxy group, yielding the corresponding cyclized products. In contrast, either conformationally favorable or flexible 1-arylalkan-3- or 4-ones easily cyclize into five- or six-membered condensed rings by treatment with SmI(2) via ketyl radical intermediates. The addition of HMPA as cosolvent dramatically changes the cyclization mode of the SmI(2)-induced reaction, and the para-cyclization products are exclusively formed. This "HMPA effect" can be rationalized by the strong chelating ability of HMPA with the samarium atom.

A new cascade radical reaction for the synthesis of biaryls and triaryls from benzyl iodoaryl ethers

The paper describes a new method of synthesizing biaryls and triaryls through an intramolecular ipso-substitution reaction initiated by the addition of an aryl radical to a benzyl ether. A tandem variant of the reaction has also been demonstrated. A short synthesis of isoaucuparin 27 , a natural product found in the sapwood tissue of Sorbus aucuparia, is also described.

Radical isomerization via intramolecular ipso substitution of N-arylamides: Aryl translocation from nitrogen to carbon

N-Aryl-N-(3-bromopropyl)amides are converted to N-(3-arylpropyl)amides under standard radical generating conditions via intramolecular ipso attack of the alkyl radicals which generates spiro cyclohexadienyl radical intermediates.

Radical isomerization via intramolecular ipso substitution of aryl ethers: Aryl translocation from oxygen to carbon

Bromopropyl aryl ethers an converted to 3-arylpropanols under standard radical generating conditions in the presence of tributylstannane and AIBN. This rearrangement involves intramolecular ipso attack of the alkyl radicals which generates spiro cyclohexadienyl radical intermediates.

ChemInform Abstract: A Novel Spiro Adduct from Intramolecular ipso Substitution in the Photolysis of an α‐(p‐(2‐Hydroxyalkoxy)phenyl)vinyl Bromide.

AbstractIrradiation of the vinyl bromide (I) in the presence of sodium isopropoxide produces the dioxaspirodecadiene (II).

A novel spiro adduct from intramolecular ipso substitution in the photolysis of an α-[p-(2-hydroxyalkoxy)phenyl]vinyl bromide

A 1,4-dioxaspiro[4.5]deca-6,9-diene was obtained in high yield by photolysis of 1-bromo-1-[p-(2-hydroxy-2-methylpropoxy)phenyl]-2,2-diphenylethene in the presence of sodium 2-propoxide.

Pyrolysis studies of some simple coal related aromatic methyl ethers

Pyrolysis of the coal related model compounds o-, m-, and p-hydroxy and methoxyanisoles has been studied under inert atmosphere at reaction temperatures from 598 to 673 K, and for reaction times from 1 to 600 min. The thermal decomposition of all these anisoles takes place via two main primary pathways, namely by demethylation of the methoxyl groups, and by an intramolecular ipso substitution of the methoxyl groups via a spiranic oxiran intermediate. The demethoxylation under mild reaction conditions obviously takes place as a secondary reaction via the ipso substitution pathway. The demethylation of o-hydroxyanisole (guaiacol) is partly concerted on the basis of kinetics and of e.p.r. measurements of the residual spin concentration of the pyrolysis products. There is, however, no indication of a concerted mechanism for 0-methoxyanisole (veratrole). The apparent first order activation energy of all the anisoles studied is of the order 240 ± 20 kJ mol −1 corresponding to the average bond energy of the methyl CO bond in the aromatic methoxyl group.

ChemInform Abstract: SYNTHESIS OF GRISA‐2′,5′‐DIEN‐3,4′‐DIONES BY INTRAMOLECULAR IPSO‐SUBSTITUTION

AbstractDie Phenoxybenzoesäureester (I) werden in Gegenwart von trockenem Chlorwasserstoff und Titantetrachlorid zu den Grisadiendionen (II) cyclisiert.

Synthesis of grisa-2′,5′-dien-3,4′-diones by intramolecular ipso-substitution

Appropriately substituted o-phenoxybenzoic esters on treatment with dry hydrogen chloride and titanium(IV) chloride in dichloromethane yield grisa-2′,5′-dien-3,4′-diones by intramolecular ipso-substitution.