Diphenyl diselenide explained

Diphenyl diselenide is the chemical compound with the formula (C₆H₅)₂Se₂, abbreviated Ph₂Se₂. This yellow-coloured solid is the oxidized derivative of benzeneselenol. It is used as a source of the PhSe unit in organic synthesis.

Preparation and properties

Ph₂Se₂ is prepared by the oxidation of benzeneselenoate, the conjugate base of benzeneselenol which is generated via the Grignard reagent:

PhMgBr + Se → PhSeMgBr

2 PhSeMgBr + Br₂ → Ph₂Se₂ + 2 MgBr₂

The molecule has idealized C₂-symmetry, like hydrogen peroxide and related molecules. The Se-Se bond length of 2.29 Å the C-Se-Se-C dihedral angle is 82° and the C-Se-Se angles are near 110°.^[1]

Medical applications

Diphenyl diselenide alleviates methylmercury poisoning in grass carp.^[2]

Reactions

A reaction characteristic of Ph₂Se₂ is its reduction:

Ph₂Se₂ + 2 Na → 2 PhSeNa

PhSeNa is a useful nucleophile used to introduce the phenylselenyl group by nucleophilic substitution of alkyl halides, alkyl sulfonates (mesylates or tosylates) and epoxides. The example below was taken from a synthesis of morphine.^[3]

Another characteristic reaction is chlorination:

Ph₂Se₂ + Cl₂ → 2 PhSeCl

PhSeCl is a powerful electrophile, used to introduce PhSe groups by reaction with a variety of nucleophiles, including enolates, enol silyl ethers, Grignard reagents, organolithium reagents, alkenes and amines. In the sequence below (early steps in the synthesis of Strychnofoline), a PhSe group is introduced by reaction of a lactam enolate with PhSeCl.^[4] This sequence is a powerful method for the conversion of carbonyl compounds to their α,β-unsaturated analogs.^[5]

Diphenyl diselenide itself is also a source of a weakly electrophilic PhSe group in reactions with relatively powerful nucleophiles like Grignard reagents, lithium reagents and ester enolates (but not ketone enolates or weaker nucleophiles). PhSeCl is both more reactive, and more efficient, since with Ph₂Se₂ half of the selenium is wasted.

Ph₂Se₂ + Nu⁻ → PhSeNu + PhSe⁻

N-Phenylselenophthalimide (N-PSP) can be used if PhSeCl is too strong and diphenyl diselenide is too weak or wasteful.^[6]

Notes and References

1. Marsh . R. E. . The Crystal Structure of Diphenyl Diselenide . 10.1107/S0365110X52001349 . Acta Crystallographica . 5 . 4 . 458–462 . 1952 . free.
2. Baldissera. Matheus D.. Souza. Carine F.. da Silva. Aleksandro S.. Henn. Alessandra S.. Flores. Erico M. M.. Baldisserotto. Bernardo. 2020. Diphenyl diselenide dietary supplementation alleviates behavior impairment and brain damage in grass carp (Ctenopharyngodon idella) exposed to methylmercury chloride. Comparative Biochemistry and Physiology. Toxicology & Pharmacology. 229. 108674. 10.1016/j.cbpc.2019.108674. 1532-0456. 31760078. 208274623.
3. Taber . D. F. . Neubert . T. D. . Rheingold . A. L. . 10.1021/ja027882h . Synthesis of (−)-Morphine . Journal of the American Chemical Society . 124 . 42 . 12416–12417 . 2002 . 12381175.
4. Lerchner, A. . Carreira, E. M. . First Total Synthesis of (±)-Strychnofoline via a Highly Selective Ring-Expansion Reaction . . 2002 . 124 . 50 . 14826–14827 . 10.1021/ja027906k . 12475306.
5. Preparation of α,β-Unsaturated Carbonyl Compounds and Nitriles by Selenoxide Elimination . Reich, H. J. . Wollowitz, S. . . 1993 . 44 . 1–296 . 10.1002/0471264180.or044.01 . 0471264180.
6. Barrero . A. F. . Alvarez-Manzaneda, E. J. . Chahboun, R. . Corttés, M. . Armstrong, V. . Synthesis and Antitumor Activity of Puupehedione and Related Compounds . . 1999 . 55 . 52 . 15181–15208 . 10.1016/S0040-4020(99)00992-8.