Halogenation of Alkyl <i>p</i>-Tolyl Sulfones with Carbon Tetrahalides. Application to the Synthesis of Aromatic Ketones

Kotake, Hiroshi; Inomata, Katsuhiko; Kinoshita, Hideki; Sakamoto, Yoko; Kaneto, Yoko

doi:10.1246/bcsj.53.3027

Cited by 17 publications

(3 citation statements)

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“…Trichloromethylsulfonyl-THIQ ( 23 ) was prepared from 38 (Scheme ). Deprotonation of the acidic methanesulfonyl group with 1 equiv of n -BuLi resulted in a monoanion which was treated with an excess of carbon tetrachloride . The resulting monochlorosulfonebeing more acidic than the trichloromethyl anionwas deprotonated and chlorinated.…”

Section: Chemistrymentioning

confidence: 99%

Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1

et al. 1998

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7-Substituted-1,2,3,4-tetrahydroisoquinolines (7-substituted-THIQs) are potent inhibitors of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28), the enzyme involved in the biosynthesis of epinephrine. Unfortunately, most of these compounds also exhibit strong affinity for the alpha2-adrenoceptor. To design a selective (PNMT vs alpha2-adrenoceptor affinity) inhibitor of PNMT, the steric and electrostatic factors responsible for PNMT inhibitory activity and alpha2-adrenoceptor affinity were investigated by evaluating a number of 7-substituted-THIQs. A classical quantitative structure-activity relationship (QSAR) study resulted in a three-parameter equation for PNMT (PNMT pKi = 0.599pi - 0.0725MR + 1. 55sigmam + 5.80; n = 27, r = 0.885, s = 0.573) and a three-parameter equation for the alpha2-adrenoceptor (alpha2 pKi = 0.599pi - 0. 0542MR - 0.951sigmam + 6.45; n = 27, r = 0.917, s = 0.397). These equations indicated that steric effects and lipophilicity play a similar role at either active site but that electronic effects play opposite roles at either active site. Two binding orientations for the THIQs were postulated such that lipophilic and hydrophilic 7-substituents would not occupy the same region of space at either binding site. Using these two binding orientations, based on the lipophilicity of the 7-substituent, comparative molecular field analysis (CoMFA) models were developed that showed that the steric and electrostatic interactions at both sites were similar to those previously elaborated in the QSAR analyses. Both the QSAR and the CoMFA analyses showed that the steric interactions are similar at the PNMT active site and at the alpha2-adrenoceptor and that the electrostatic interactions were different at the two sites. This difference in electrostatic interactions might be responsible for the selectivity of THIQs bearing a nonlipophilic electron-withdrawing group at the 7-position. These QSAR and CoMFA results will be useful in the design of potent and selective (PNMT vs alpha2-adrenoceptor affinity) inhibitors of PNMT.

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Section: Chemistrymentioning

confidence: 99%

Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1

et al. 1998

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“…H3C-o-S02CHNa Existem também na literatura estudos envolvendo a polialogenação de carbânions de sulfonas com tetraaletos de alquila 23 ,24. Assim, Inomata e col. 23 mostraram que a etil p-tolil sulfona (17) reage com quantidade equimolar de n-BuLi a -78°C em THF, gerando o respectivo carbânion que, após tratamento com excesso de tetracloreto de carbono, fornece a sulfona diclorada 18 correspondente (esquema 6). Por outro lado, Daweyko e Regis25, ao utilizarem o sistema NaOH / DMF (N,N-dimetilformamida) em reações de halogenação de uma série de sulfonas empregando tetracloreto de carbono como agente clorante, obtiveram como produto apenas as sulfonas monocloradas correspondentes em rendimentos que variaram de 68-96%.…”

Section: Esquemaunclassified

“…Por outro lado, Daweyko e Regis25, ao utilizarem o sistema NaOH / DMF (N,N-dimetilformamida) em reações de halogenação de uma série de sulfonas empregando tetracloreto de carbono como agente clorante, obtiveram como produto apenas as sulfonas monocloradas correspondentes em rendimentos que variaram de 68-96%. 23 Kotake, H. ; Inomata, K. ; Kinoshita, H. ; Sakamoto, Y; Kaneto, H., Buli. Chem.…”

Section: Esquemaunclassified

Reações de α-sulfonil carbânions: alquilação e sulfenilação de alguns α-sulfonil tioésteres. Descarboxilação alquilativa dos ácidos α-fenilsulfonil-α-fenilpropanóicos racêmico e opticamente ativo

Neves¹

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Preparation of Ketones

1984

Compendium of Organic Synthetic Methods

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Halogenation of Alkyl p-Tolyl Sulfones with Carbon Tetrahalides. Application to the Synthesis of Aromatic Ketones

Abstract: Carbanions of alkyl p-tolyL sulfones reacted with carbon tetrahalides to give the corresponding polyhalogenated products in good yields. Some chlorinated sulfones were converted to unsymmetrical ketones by treatment with silver perchlorate in trifluoroacetic acid.

Cited by 17 publications

References 7 publications

Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1

Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1

Reações de α-sulfonil carbânions: alquilação e sulfenilação de alguns α-sulfonil tioésteres. Descarboxilação alquilativa dos ácidos α-fenilsulfonil-α-fenilpropanóicos racêmico e opticamente ativo

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Halogenation of Alkyl p-Tolyl Sulfones with Carbon Tetrahalides. Application to the Synthesis of Aromatic Ketones

Abstract: Carbanions of alkyl p-tolyL sulfones reacted with carbon tetrahalides to give the corresponding polyhalogenated products in good yields. Some chlorinated sulfones were converted to unsymmetrical ketones by treatment with silver perchlorate in trifluoroacetic acid.

Cited by 17 publications

References 7 publications

Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α2-Adrenoceptor,1

Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α2-Adrenoceptor,1

Reações de α-sulfonil carbânions: alquilação e sulfenilação de alguns α-sulfonil tioésteres. Descarboxilação alquilativa dos ácidos α-fenilsulfonil-α-fenilpropanóicos racêmico e opticamente ativo

Preparation of Ketones

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Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1

Synthesis, Biochemical Evaluation, and Classical and Three-Dimensional Quantitative Structure−Activity Relationship Studies of 7-Substituted-1,2,3,4-tetrahydroisoquinolines and Their Relative Affinities toward Phenylethanolamine N-Methyltransferase and the α₂-Adrenoceptor^,1