Benzeneselenenyl Chloride Research Articles

ChemInform Abstract: Formation and Electrophilic Reactions of Benzeneselenenyl p- Toluenesulfonate. Preparation and Properties of Addition Products with Acetylenes.

Benzeneselenenyl p-toluenesulfonate (1) was generated in situ by the reaction of silver p-toluenesulfonate with benzeneselenenyl chloride in acetonitrile. The reagent reacted with acetylenes by electrophilic 1,2-addition to afford the β-(phenylseleno)vinyl p-toluenesulfonates 2−12, generally in high yield. Selenenyl sulfonate 1 was also unexpectedly produced via radical pathways by heating p-toluenesulfonic acid with AIBN in the presence of diphenyl diselenide, or from the pyrolysis of sulfinyl sulfone 15 with the diselenide. The regioisomeric adducts 3 and 4 were prepared from 1 and 1-decyne, and both underwent elimination with potassium tert-butoxide to afford the acetylenic selenide 19 initially, which isomerized to a 6:1 mixture of the propargylic and allenic selenides 20 and 21 upon further equilibration

On the Mechanism of the Selenolactonization Reaction with Selenenyl Halides

The mechanism of selenocyclization reactions of beta,gamma-unsaturated acids and their derivatives has been studied. The reactions of (E)-4-phenyl-3-butenoic acid 10 and its silyl and alkyl esters with benzeneselenenyl chloride (PhSeCl) and bromide (PhSeBr) have been examined by VT-NMR and in situ IR spectroscopic methods. Whereas the reactions of the acid 10 in the presence of a base were irreproducible and complicated, reactions of the silyl esters were clean and spontaneously and quantitatively afforded a chloroselenylation adduct at -70 degrees C as a single (Markovnikov) isomer. This adduct underwent three processes as the temperature was raised: (1) reversal to the starting materials, (2) isomerization to the anti-Markovnikov product, and (3) cyclization to the selenolactone 12. All of these processes are believed to proceed via a seleniranium ion the intermediacy of which was established by independent synthesis and spectroscopic identification. The reversible formation of chloro selenide adducts was unambiguously established by crossover experiments. The reaction of 10 with PhSeBr was found to be rapid but thermodynamically unfavorable at room temperature.

Regio‐ and Stereoselective Methoxyselenenylation of Chiral 2‐Vinyl Perhydro‐1,3‐benzoxazines Promoted by Selenium‐Heteroatom Nonbonded Interactions.

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1,4-Asymmetric Induction in Methoxyselenenylation of Double Bonds at the Nitrogen Side of Chiral Perhydro-1,3-benzoxazines Promoted by Nonbonded Se···N Interactions

Regio- and diastereoselective methoxyselenenylation of cinnamylamines attached to a chiral perhydrobenzoxazine occurs in high yields by reaction with benzeneselenenyl chloride in dichloromethane-methanol. The diastereoselection is dependent on the temperature of the reaction and the structure of the substituent at C-2 and can be rationalized by accepting a 1,4-asymmetric induction process after coordination of the selenium to the nitrogen atom of the allylamine system.

Regio- and Stereoselective Methoxyselenenylation of Chiral 2-Vinyl Perhydro-1,3-benzoxazines Promoted by Selenium-Heteroatom Nonbonded Interactions

Regio- and diastereoselective methoxyselenenylations of double bonds attached to the N,O-ketalic carbon of chiral perhydrobenzoxazines occur in high yields by reaction with benzeneselenenyl chloride in dichloromethane-methanol. The diastereoselection is dependent on the reaction conditions and the structure of the starting compounds and can be rationalized by accepting the coordination of the selenium to the oxygen atom of the heterocycle.

Reactions of Tris(2‐pyridyl)phosphine Oxides with Electrophiles: Formation of 5‐Substituted 2,2′‐Bipyridyls.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Reactions of tris(2‐pyridyl)phosphine oxides with electrophiles: Formation of 5‐substituted 2,2′‐bipyridyls

AbstractThe reaction of tris(2‐pyridyl)phosphine oxides with benzeneselenenyl chloride in methanol gave the corresponding 5‐phenylseleno‐2,2′‐bipyridyls together with a small amount of 2,2′‐bipyridyls. Similarly, the reaction with arenesulfenyl chlorides in aqueous acetonitrile afforded two kinds of coupling products, 5‐phenylthio‐2,2′‐bipyridyls and 2,2′‐bipyridyls. While in the reaction with arenesulfinyl chlorides in aqueous acetonitrile, four corresponding bipyridyl derivatives, 2,2′‐bipyridyls, 5‐arylthio‐2,2′‐bipyridyls, 5‐arylsulfinyl‐2,2′‐bipyridyls, and 5‐arylsulfonyl‐2,2′‐bipyridyls, were formed. © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:72–81, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10085

Ring-opening reactions of cyclopropanes. Part 7.1 Selenenylation and cyanoselenenylation of ethyl 2,2-dimethoxycyclopropanecarboxylates

The uncatalyzed reaction of C3-substituted cyclopropanes 1b–d with benzeneselenenyl chloride 3 leads to 1-ethyl 4-methyl 2-(phenylseleno)butanedioates 5b–d while the unsubstituted 1a gives the 3-phenylseleno derivative 6a. Formation of 5b–d occurs regio- and stereoselectively via electrophilic ring-opening of 1 while 6a results from the selenenylation of the alkene 2a formed via isomerization of 1a. The presence of TiCl4 influences the stereochemistry of the reaction with chloride 3 while it is essential for reaction of the less reactive PhSeCN 4. With this electrophile the reactions lead to α,α-dimethoxycarbonitriles 13a–d while only 1a and 1b give also the expected cyanoselenenyl derivatives 12a and 12b. Moreover, from 1b compound syn- 5b is obtained, and 1a gives, via the alkene 2a, esters 14a and 6a. A mechanistic interpretation suggests the intermediacy of well-stabilized dipolar species 9 which should be formed by coordination of the Lewis acid to the carbonyl oxygen of 1 and subsequent ring opening.

The Reactions of N-Substituted 2-(Dimethylallyl)aniline Compounds with Phenylselanyl Halides

Cyclization of the carbamate of 2-(dimethylallyl)aniline with phenylselanyl chloride (benzeneselenenyl chloride) gave a 1 : 1 mixture of a dihydroindole and a tetrahydroquinoline. With phenylselanyl bromide only the dihydroindole was obtained. Addition of methanol to the silica used in the procedure trapped the reaction at the non-cyclized stage forming a 3-methoxy-3-methyl-2-(phenylselanyl)butyl side chain. The sulfonamide of 2- (dimethylallyl)aniline only formed the dihydroindole with phenylselanyl chloride. The corresponding trifluoroacetamide derivative did not form any cyclized product under the same conditions. The dihydroindole could be converted into the corresponding alkene by oxidative removal of the phenylseleno group. 4-Ethoxycarbonyl-2-(3,3-dimethylallyl)aniline cyclized with mercuric nitrate to give, after a reductive workup, a 2,2-dimethyltetrahydroquinoline. The X-ray crystal structures of ethyl N-{2-[3-methoxy-3-methyl-2- (phenylselanyl)butyl]phenyl}carbamate and 2-[1-methyl-1-(phenylselanyl)ethyl]-1-[(4-methylphenyl)sulfonyl]-indoline are reported.

Selenium redox biochemistry of zinc-sulfur coordination sites in proteins and enzymes.

Selenium has been increasingly recognized as an essential element in biology and medicine. Its biochemistry resembles that of sulfur, yet differs from it by virtue of both redox potentials and stabilities of its oxidation states. Selenium can substitute for the more ubiquitous sulfur of cysteine and as such plays an important role in more than a dozen selenoproteins. We have chosen to examine zinc-sulfur centers as possible targets of selenium redox biochemistry. Selenium compounds release zinc from zinc/thiolate-coordination environments, thereby affecting the cellular thiol redox state and the distribution of zinc and likely of other metal ions. Aromatic selenium compounds are excellent spectroscopic probes of the otherwise relatively unstable functional selenium groups. Zinc-coordinated thiolates, e.g., metallothionein (MT), and uncoordinated thiolates, e.g., glutathione, react with benzeneseleninic acid (oxidation state +2), benzeneselenenyl chloride (oxidation state 0) and selenocystamine (oxidation state -1). Benzeneseleninic acid and benzeneselenenyl chloride react very rapidly with MT and titrate substoichiometrically and with a 1:1 stoichiometry, respectively. Selenium compounds also catalyze the release of zinc from MT in peroxidation and thiol/disulfide-interchange reactions. The selenoenzyme glutathione peroxidase catalytically oxidizes MT and releases zinc in the presence of t-butyl hydroperoxide, suggesting that this type of redox chemistry may be employed in biology for the control of metal metabolism. Moreover, selenium compounds are likely targets for zinc/thiolate coordination centers in vivo, because the reactions are only partially suppressed by excess glutathione. This specificity and the potential to undergo catalytic reactions at low concentrations suggests that zinc release is a significant aspect of the therapeutic antioxidant actions of selenium compounds in antiinflammatory and anticarcinogenic agents.

Additions of Organocopper Reagents and Heteroatom Nucleophiles to 1-Phenylseleno-2-(p-toluenesulfonyl)ethyne. Preparation of Vinyl and Allenic Sulfones and Formation of Michael, Anti-Michael, and Rearrangement Products

1-Phenylseleno-2-(p-toluenesulfonyl)ethyne (4) was produced nearly quantitatively from p-(toluenesulfonyl)ethyne and benzeneselenenyl chloride. It underwent stereo- and regioselective syn-additions of organocopper reagents RCu(CN)Li to the β-position of the sulfone moiety to afford adducts 5. Further reaction of the products with reagents RCu(SePh)Li resulted in substitution of the phenylseleno group with retention of configuration. Control of E,Z-stereochemistry in the product β,β-disubstituted vinyl sulfones is therefore achieved by the order of addition of the reagents. Selenoxide syn-elimination of adducts 5 afforded the corresponding allenic sulfones. The additions of amines and alkoxides to 4 produced the corresponding anti-Michael regioisomers (where attack occurred α to the sulfone group) as the major or sole products. The additions were highly stereoselective, proceeding by anti-addition in the anti-Michael series and by syn-addition in the corresponding Michael regioisomers. The reactions of 4 with thiolates and selenolates were more complex, affording rearranged adducts and Michael adducts as the major and minor products, respectively. The formation of the rearranged products can be rationalized by a series of addition−elimination processes. Phenylselenoethyne (43) underwent conjugate additions of pyrrolidine, sodium methoxide, sodium ethanethiolate, and benzeneselenolate anion, affording the corresponding cis isomers via anti-addition. The experiments with heteroatom nucleophiles and acetylenes 4 and 43 show that the phenylseleno group has a surprisingly large activating effect upon conjugate additions.

Synthesis and Substitution Reactions of N-Protected 2-(Phenylselenonylmethyl)pyrrolidines

Alkyl phenyl selenides derived from the benzeneselenenyl chloride induced cyclization of N-protected pent-4-enylamines can be converted in good yield into the corresponding 2-hydroxymethyl- or 2- alkoxymethyl-substituted pyrrolidines by oxidation to the corresponding selenone, followed by reaction with water (or hydroxide) or with the corresponding alcohol. Details of the reactions and possible mechanisms for the substitution are discussed.

Molecular and electronic structure of benzeneselenenyl molecules and cations

AbstractMolecular and electronic structures of a select group of molecules and cations, including benzeneselenenyl chloride, benzeneselenenyl bromide, and benzeneselenol have been studied using ab initio calculations at the Hartree–Fock and MP2 levels of theory. Very few experimental data are available for this class of compounds. The properties and structures of these molecules are compared. © John Wiley & Sons, Inc.

ChemInform Abstract: Cyclization of Hex‐5‐enylcarbamates and Related Compounds with Benzeneselenenyl Chloride and Some Reactions of the 2‐Substituted Piperidine Products.

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1-(Phenylseleno)-2-(p-toluenesulfonyl)ethyne. A Novel Acetylenic Sulfone That Undergoes Normal and Anti-Michael Nucleophilic Additions

1-(Phenylseleno)-2-(p-toluenesulfonyl)ethyne (3) was prepared from p-toluenesulfonyl-ethyne and benzeneselenenyl chloride in the presence of triethylamine. It undergoes sequential conjugate addition and substitution of the selenium moiety with higher order cuprates, and preferential anti-Michael additions with amines, alkoxides, thiolates or selenolates.

1-(Phenylseleno)-2-(p-toluenesulfonyl)ethyne. A novel acetylenic sulfone that undergoes normal and anti-Michael nucleophilic additions

1-(Phenylseleno)-2-(p-toluenesulfonyl)ethyne ( 3) was prepared from p-toluenesulfonyl-ethyne and benzeneselenenyl chloride in the presence of triethylamine. It undergoes sequential conjugate addition and substitution of the selenium moiety with higher order cuprates, and preferential anti-Michael additions with amines, alkoxides, thiolates or selenolates.

The Cyclization of Hex-5-Enylcarbamates and Related Compounds With Benzeneselenenyl Chloride and Some Reactions of the 2-Substituted Piperidine Products

The reaction of hex-5-enylcarbamates with benzeneselenenyl chloride gives adducts which cyclize , in the presence of silica or stannic chloride, to 2-phenylselenomethylpiperidine-1-carboxylates. The corresponding selenoxides eliminate to form 2-methylenepiperidine derivatives which are unstable, both thermally and on silica. The selenoxides also undergo a Pummerer-type reaction to form 2-acetoxy( phenylseleno ) methylpiperidine systems which can be oxidatively converted into a piperidine 2-aldehyde. The selenoxides react with carbon tetrachloride in base to form a 2,2,2-trichloroethyl substituent . Both the selenoxides and the phenylseleno groups of the cyclized products can be displaced by nucleophiles. Ethyl hept-6-enylcarbamate did not give a cyclic product with benzeneselenenyl chloride and silica, and gave a poor yield of a hexahydroazepine with stannic chloride. Hex-5-enamide cyclized to give a lactone, rather than a lactam , product. Hex-5-enenitrile gave Ritter reaction products with benzeneselenenyl chloride in acetonitrile , and a dimer in non- nucleophilic solvents.

Phenylselenenyl- and phenylthio-substituted pyrimidines as inhibitors of dihydrouracil dehydrogenase and uridine phosphorylase.

Lithiation of 5-bromo-2,4-bis(benzyloxy)pyrimidine (3) with n-BuLi at -80 degrees C followed by the addition of diphenyl diselenide or diphenyl disulfide as an electrophile furnished the corresponding 5-(phenylhetera)-2,4-bis(benzyloxy)pyrimidine, which on exposure to trimethylsilyl iodide in CH2-Cl2 at room temperature yielded the 5-(phenylhetera)uracils in 70-75% yield. Similarly, the 6-(phenylhetera)uracils were prepared from 6-bromo-2,4-bis(benzyloxy)pyrimidine (10). 1-[(2-Hydroxyethoxy)methyl]-5-(phenylselenenyl)uracil (PSAU, 18) and 1-(ethoxymethyl)-5-(phenylselenenyl)uracil (17) were synthesized by the electrophilic addition of benzeneselenenyl chloride to the acyclic uracils under basic conditions. These compounds were evaluated for their ability to inhibit dihydrouracil dehydrogenase (DHUDase, E.C. 1.3.1.2), orotate phosphoribosyltransferase (OPRTase, E.C. 2.4.2.10), uridine phosphorylase (UrdPase, E.C. 2.4.2.3), and thymidine phosphorylase (dThdPase, E.C. 2.4.2.4). 5-(Phenylselenenyl)uracil (PSU, 6) and 5-(phenylthio)uracil (PTU, 7) inhibited DHUDase with apparent K(i) values of 4.8 and 5.4 microM, respectively. The corresponding 6-analogues, compounds 13 and 14, demonstrated inhibitory activity against OPRTase. PTU as well as PSU and its riboside, 2'-deoxyriboside, and acyclonucleosides were inhibitors of UrdPase, with PSAU (18) being the most potent with an apparent K(i) value of 3.8 microM. None of the compounds evaluated had any effect on dThdPase. Interestingly, most of the compounds showed modest selective anti-human-immunodeficiency-virus activity in acutely infected primary human lymphocytes.

Mechanism and stereochemistry of the enzyme-catalysed formation of a 2,2-dimethylchromene ring from a prenylated phenol: conversion of rot-2′-enonic acid into deguelin by deguelin cyclase

The stereochemistry of the enzymic conversion of rot-2′-enonic acid into deguelin, mediated by deguelin cyclase, has been studied. Using both an enzyme preparation and seedlings of Tephrosia vogellii, it is shown that (6aS,12aS,5′R/S)-5′-hydroxy-4′,5′-dihydro[6′,6′-C3H3]deguelin is not an acceptable intermediate: no evidence for other oxygenated intermediates was found.The (pro-R)- and (pro-S)-6′-methyl groups of deguelin were identified by synthesis from [(E)-4′-13C]rot-2′-enonic acid. Addition of benzeneselenenyl chloride gives two diastereoisomeric 5′-(phenyl selenides) of 4′,5′-dihydrodeguelin which are separated and their stereochemistry established by X-ray crystallography. Elimination of selenoxide from the (5′S)-stereoisomer then gives (6′R)-deguelin (δc 28.20): (6′S)-deguelin has δc 28.52.Although a chemical conversion of [4′-13C]rot-2′-enonic acid into labelled deguelin produces a 1:1 distribution of label between the (pro-R)- and (pro-S)-6′-methyls, the enzyme-mediated conversion results unexpectedly in a 76% incorporation into the (pro-R)- and 24% into the (pro-S)-form. The stereochemistry of the removal of the key 1′-hydrogens in rot-2′-enonic acid was therefore examined.Addition of benzenesulfenyl chloride to deguelin gave a highly reactive chloro sulfide by syn-addition through attack from the less hindered β-face of the molecule. Treatment with sodium cyanoborohydride displaced the reactive chlorine with complete inversion to give (6aS,12aS,5′S)-5′-phenylthio-4′,5′-dihydrodeguelin. Ring-E scission of the latter proceeded satisfactorily using sodium naphthalenide only after reduction of the 1,2-carbonyl to the alcohol: periodinane oxidation then produced rot-2′-enonic acid. Replacement of the unlabelled cyanoborohydride by cyanoborotritide gave the desired (6aS,12aS,1′S)-[1′-3H]rot-2′-enonic acid. The (6aS,12aS,1′R)-[1′-3H]-counterpart was made by first preparing [4′-3H]deguelin by syn-elimination from the sulfoxide formed from (6aS,12aS,4′R,5′S)-5′-phenylthio-4′,5′-dihydro-[4′-3H] deguelin. Addition of benzenesulfenyl chloride to the [4′-3H]deguelin, followed by a sequence parallelling that above, using unlabelled sodium cyanoborohydride, gave the required (6aS,12aS,1′R)-[1′-3H]rot-2′-enonic acid.Enzymic conversion of each [3H]-labelled rot-2′-enonic acid into deguelin along with a [14C]-labelled monitor, shows that a 73% loss of (pro-4′S-H) in rot-2′-enonic acid correlates with a 76% attainment of a (pro-6′R-Me) in deguelin, whilst a 27% loss of (pro-4′R-H) in the former correlates with a 24% attainment of a (pro-6′S-Me) in the latter. The possible enzymic mechanism of the reaction is discussed and related to a similar mechanism we have suggested for the enzymic formation of rotenone from rot-2′-enonic acid.

Facile Access to 2-Alkylidene 3-Oxy Propanals and Propionic Acids from Conjugated Enals

Abstract Conjugated enals or their methyl acetals react with benzeneselenenyl chloride in the presence of an oxygen nucleophile to give Michael-type adducts. The latter are oxidized into 2-alkylidene 3-oxy propanals and propionic acids.