Benzeneselenol1

[645-96-5]  · C6H6Se  · Benzeneselenol  · (MW 157.07)

(a source of selenolate ions; a selenation reagent for organic halides, alcohols, amines, ethers, alkynes, and carbonyl compounds; a mild reducing agent)

Physical Data: bp 73-74 °C/20 mmHg.

Solubility: sol benzene, Et2O, THF, acetonitrile; insol H2O, but sol aq NaOH.

Preparative Methods: benzeneselenol is synthesized by the reaction of Phenylmagnesium Bromide with metallic Selenium, followed by quenching with aqueous hydrochloric acid.2a Similar hydrolysis of sodium selenolate prepared by the reduction of Diphenyl Diselenide with Sodium Borohydride is a convenient alternative.2b In addition, Phenyl Trimethylsilyl Selenide can be employed as a useful precursor of benzeneselenol upon treating with methanol.2c Purification of benzeneselenol is performed by distillation under reduced pressure. 1H NMR (CDCl3) d 1.54 (PhSeH); 13C NMR (CDCl3) d 124.46, 126.45, 129.26, 132.71 (PhSeH).

Handling, Storage, and Precautions: pure benzeneselenol is a colorless liquid, but, on exposure to air, the liquid turns yellow to an extent that depends on the concentration of diphenyl diselenide formed by air-oxidation of PhSeH. Thus, it should be stored under nitrogen in the dark, and is conveniently handled using syringe technique. Use in a fume hood.

Generation of Phenylselenolate Ions.

Benzeneselenol has greater acidity than benzenethiol (pKa = 5.9 (PhSeH); 6.5 (PhSH)),2b and therefore it gives lithium or sodium phenylselenolates in the presence of bases such as MeLi (in Et2O),3a NaH (in THF),3b,c and aq NaOH.3d Alternatively, phenylselenolate ions are prepared by the reduction of Diphenyl Diselenide with NaBH4 (in EtOH or DMF),4 Na (in THF, HMPA, or liq NH3),3b,c,5 or NaH (in THF or DMF).6 Sodium selenolate prepared by the NaBH4 reduction of (PhSe)2 is considered to be a complex with triethyl borate of the form Na+[PhSeB(OEt)3]-,4c and indeed has lower nucleophilicity in comparison with uncomplexed PhSeNa generated by the reduction of (PhSe)2 with Na (or NaH).3b,c The selenolate ions are generally much more sensitive to air (molecular oxygen) compared with PhSeH itself. The oxidation of PhSeH or its anions by air or other oxidizing agents such as H2O2 or Br2 provides a general method for synthesis of diphenyl diselenide,7 which is a key intermediate compound for preparation of various organoselenium reagents.

Substitution Reactions.

The selenolate ions generated are widely utilized as reagents for introducing a PhSe group into organic molecules. For example, nucleophilic substitution of organic halides by selenolates leads to the corresponding selenides in good yields (i.e. RX + PhSe- -> RSePh + X-).5a,8 A similar reaction using acid halides affords selenoesters,9 which are utilized as precursors of acyl radicals (eq 1).10

Organic sulfonates also undergo displacement by PhSe- to give selenides.5a,11 Amines can be converted into selenides via the nucleophilic displacement of corresponding ditosylamides by selenolate ions (i.e. RNH2 -> RNTs2 -> RSePh),12 or by reaction with benzeneselenol at high temperatures.2b

Upon treatment of esters with selenolate ions, alkyl-oxygen cleavage reaction occurs to provide carboxylic acids and alkyl selenides (i.e. RCOORŽ + PhSe- -> RCOOH + PhSeRŽ).3b,c The use of lactones as the substrates leads to the synthesis of o-phenylselenenyl carboxylic acids.4b,5b,6,13 Ring-opening of epoxides also takes place by PhSe- to give b-hydroxy selenides,14a-c which can be converted into allylic alcohols via oxidative elimination of the phenylseleno group (eq 2).4a Acyclic ethers undergo C-O bond cleavage upon a similar treatment.14d Furthermore, C-C bond cleavage of activated cyclopropanes by PhSe- can proceed efficiently.15

The ring-opening of epoxides16a and the alkyl-oxygen cleavage of esters are also attained by the use of benzeneselenol under acidic conditions. For example, alkyl acetates are converted to the corresponding selenides by the assistance of BF3.Et2O (i.e. ROAc + PhSeH -> RSePh).16b,c Direct transformation of alcohols to selenides is possible by treatment with PhSeH in the presence of H2SO4, HCl, ZnCl2, or BF3.Et2O (i.e. ROH + PhSeH -> RSePh).17

Other preparative methods of selenides using selenolate ions are the transition metal-catalyzed reactions with organic halides18a-c or amines,18d and the photostimulated SRN1 reactions with aryl or some alkyl halides.19

Addition Reactions.

In general, addition of benzeneselenol to unactivated alkenes20a hardly proceeds. However, if the alkenes bear a conjugated carbonyl group, such as -CHO, -C(O)R, -COOR, etc., the selenol adds smoothly under acidic,20b basic,20c-f or neutral2c conditions. Similarly, addition to conjugate dienes occurs under neutral conditions to give mainly 1,4-adducts.21 In the presence of an optically active base such as an alkaloid, the addition of PhSeH to enones proceeds with asymmetric induction (eq 3).20f

Addition of benzeneselenol to alkynes is a useful tool for the synthesis of vinylic selenides. Under neutral conditions, the addition is initiated by a trace amount of oxygen contained in the reaction system, and proceeds by a radical chain mechanism. In this case, anti-Markovnikov-type adducts are formed exclusively (eq 4).22 Contrary to this, when the same reaction is conducted in the presence of a catalytic amount of Palladium(II) Acetate, Markovnikov-type adducts are obtained selectively in place of anti-Markovnikov adducts.23 When the oxygen-induced radical reaction of allenes with PhSeH is examined, vinylic selenides are formed via the selective attack of PhSe&bdot; at the central carbon atom of allenes.24

Lewis acid-assisted addition of benzeneselenol to aldehydes and ketones affords synthetically important selenoacetals, which serve as precursors of a-selenoalkyllithiums (eq 5).25

Reduction.

Benzeneselenol is not only a selenation reagent as described above, but is also utilized as a mild reducing agent for various classes of organic compounds. The reduction of the carbon-carbon double bond of a,b-unsaturated carbonyl compounds with PhSeH is caused by an introduction of molecular oxygen into the reaction system26a or by irradiation with a sunlamp.26b The reduction proceeds by a radical chain mechanism, as illustrated in eq 6.

By a similar radical chain mechanism, aromatic aldehydes are reduced to benzylic alcohols at room temperature.26c In these reactions, no oxygen incorporation products are formed. This is due to the extremely high hydrogen-donating ability of PhSeH (the rate constant of hydrogen transfer from PhSeH to carbon radicals is estimated as 2.0 × 109 M-1 s-1 at 20 °C in THF).27

In addition, benzeneselenol reduces some nitrogen-containing functional groups such as nitro (NO2), azo (N=N), and imino groups (C=N) to corresponding amino groups.28 Organic sulfoxides are reduced to sulfides by treatment with PhSeH as exemplified in eq 7.29

Related Reagents.

Methanethiol; Methaneselenol; Thiophenol.


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Noboru Sonoda & Akiya Ogawa

Osaka University, Osaka, Japan



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