[6486-05-1]  · CH4Se  · Methaneselenol  · (MW 95.01)

(powerful nucleophilic species able to produce methaneselenolates and methyl selenides including functionalized ones; methaneselenol and methaneselenolates are valuable reducing agents)

Physical Data: bp 25.5 °C.1a

Solubility: sol most organic solvents.

Form Supplied in: sealed ampoule.

Analysis of Reagent Purity: as stable, benzene-soluble MeSe-DNP selenides using Sanger's reagent (1-fluoro-2,4-dinitrobenzene, FDNB) in DMF.2,3 The molecular ion of MeSe-DNP is prominent in the spectra (m/e 262, with selenium fragments at 247 (-Me) and 169 (-2NO2); a peak corresponding to the loss of MeSe is not observed).3 TLC plate (including its visualization)2,3 and HPLC2 of MeSe-DNP are described.

Handling, Storage, and Precautions: volatile, bad smelling compound; use only in a fume hood. Store in cold room. Destroy by slow addition to a cold aqueous solution of NaOCl in the presence of an organic solvent. Clean the vessel with aqueous solution of NaOCl.

General Considerations.

Methaneselenol is a volatile, bad smelling liquid usually prepared by reduction of dimethyl diselenide (prepared from elemental selenium, aqueous KOH and potassium bisulfite) with Hypophosphorous Acid (H3PO2) or by acid hydrolysis of methaneselenolates (eq 1).4,5 Methaneselenolates are prepared from Methyllithium or methylmagnesium iodide and elemental Selenium6 or from methaneselenol and bases (such as K2CO3,7 NEt3, pyridine,4 KOH, or NaH) or more conveniently by reduction of dimethyl diselenide with Sodium Borohydride8,9 or with metal hydrides (eqs 1 and 2).10 The synthesis of a series of methylseleno derivatives of Group 14 has been achieved6 from methaneselenol with Group 14 amines or halides or on reaction of the latter compounds with methylselenolithium, methylselenomagnesium iodide, lithium tetra(methylseleno)aluminate, or methylseleno(trimethyl)silane.

Methaneselenol and the corresponding metal selenolates are powerful nucleophiles and in some cases act as reducing agents. Although methaneselenol is easily oxidized by oxygen present in air to dimethyl diselenide, the reaction is best achieved using Hydrogen Peroxide (stoichiometric),11 methaneseleninic acid,11 or Sodium Perborate, (eq 3).12 Use of an excess of hydrogen peroxide leads to methaneseleninic acid or methaneperseleninic acid, depending upon the amount of reagent used.11,13

Reactions of Methaneselenol.

Methaneselenol reacts with alcohols in the presence of an acid catalyst to form methyl selenides (eq 4).14,15 The reaction, which is best achieved in the presence of Zinc Chloride, only occurs with those alcohols which can form an intermediate carbenium ion, such as tertiary alcohols,16 s-allyl and t-allyl alcohols,15-18 and benzyl alcohols.14,16 This reaction is used to form t-alkyl methyl selenides which cannot be prepared efficiently from methaneselenolates and alkyl halides. Methaneselenol reacts with ethylene oxide to produce 2-methylselenoethanol.19

Methaneselenol (1 equiv) and Hydrobromic Acid or Hydrochloric Acid also react with aldehydes to form a-haloalkyl selenides (45-54% yields) and small amounts (20%) of selenoacetals.20 The synthesis of the latter, which proved to be particularly valuable starting materials for the synthesis of a-selenoalkyllithiums,21-23 is achieved by reaction of methaneselenol (2 equiv) with aldehydes or ketones in the presence of an acid catalyst (eq 5).24 Best results are usually obtained using zinc chloride (0.5 equiv), although Titanium(IV) Chloride (0.3 equiv) is best used for aromatic or hindered carbonyl compounds (eq 5).24 Reduction leading to methyl selenides occurs from aromatic ketones and with ketones when the reaction is carried out with an excess of zinc chloride for a long time (eq 5).24,25 The reaction has been successfully used for the synthesis of a large variety of selenoacetals,16,21,23,24,26-35 including those derived from (a) cyclanones (4-7 membered), b-chloropropanal (HCl, 20 °C, 65% yield), which proved to be a valuable precursor of 1,1-bis(methylseleno)cyclopropane,31 and (b) unsaturated carbonyl compounds which afford, besides the expected unsaturated selenoacetals, products resulting from 1,4-addition.36 Straight-chain enals and enones mainly lead to selenoacetals,36 whereas cyclic enones produce 1,3-bis(methylseleno)propenes.36 Modification of this method allows the direct synthesis of 2-methylseleno-2-phenylthiopropane from propanal, methaneselenol, benzenethiol (1 equiv each), and zinc chloride and of 1-methoxy-1-methylselenodecane from decanal, methaneselenol (1 equiv each), methanol, and Boron Trifluoride Etherate in THF.37

Acetals also produce selenoacetals under closely related conditions. Best results are obtained with BF3.OEt2 as catalyst on straight-chain derivatives (eq 6)37 and with ZnCl2 on 1-ethoxy-1-trimethylsilyloxycyclopropane (eq 7 60% yield).38 Extension of this reaction to orthoesters leads to selenoorthoesters (eq 8).39

Reactions of Methaneselenolates.

Methaneselenolates are excellent nucleophiles which react with a large variety of organic halides and usually provide the corresponding methyl selenides (eq 9).1a,1b,10,40,41 However, primary benzyl halides, especially iodides bearing a nitro group on the aromatic ring, suffer significant reduction to the corresponding arylalkane.42 Potassium or sodium methaneselenolates react with (a) a,a-dihalomethanes which leads to 1,1-bis(methylseleno)methane (MeSeK, CH2I2 or CH2Br2, EtOH, 20 °C, 76%30 or CH2Cl2, phase-transfer catalysis, MeSeNa, Et4N+Cl-, DMF, 93%),43 (b) aromatic halides bearing an electron-withdrawing group on the aromatic ring such as 4,6-dibromoisophthalaldehyde (DMF, 20 °C, 12 h, 74%)7 and ethyl 2-chloronicotinate (EtOH, reflux, 1 h, 88%)44 to furnish 4,6-dimethylselenoisophthalaldehyde and ethyl 2-methylselenonicotinate, respectively (eq 10). b-Halo- and b-selenoalkyl halides do not produce the corresponding selenides but instead lead to alkenes (eq 11).45 This reduction reaction is stereospecific with vic-dibromides and occurs by a formal antiperiplanar elimination reaction.

Methaneselenolates react with epoxides8,9 and diethyl cyclopropane-1,1-dicarboxylate46 to produce b-hydroxyalkyl methyl selenides and g-methylselenobutyrates, respectively (eq 12). In HMPA or DMF they deprotect47,48 aryl methyl ethers, sulfides, and selenides, producing the corresponding phenolates, arylthiolates, and arylselenolates (eq 13).

Methaneselenol, in the presence of pyridine, selectively adds to a,b-unsaturated aldehydes and ketones49 and reacts with acid chlorides to produce the corresponding methylselenoesters.4 If the reaction is performed in the presence of Chlorotrimethylsilane, the intermediate enolates are trapped and g-methylseleno-1-silyloxyalkenes are isolated.50

Methaneselenol or its sodium salt react with imidates or chloroimidates, respectively, and produce selenoimidates in poor (15%) to moderate (40-50%) yields.51 Finally, Beckmann rearrangement of oxime O-sulfonates with simultaneous nucleophilic trapping of the imino carbocation intermediate by aluminum selenolate provides a new and highly efficient route to imino selenoethers (eq 14).52

Related Reagents.

Benzeneselenol; Methanethiol; Phenyl Trimethylsilyl Selenide.

1. (a) Rheinboldt, H. MOC 1955, 9, 917. (b) Organic Selenium Compounds: Their Chemistry and Biology; Klayman, D. L.; Günther, W. H. H., Eds.; Wiley: New York, 1973, p 1. (c) Krief, A.; Hevesi, L. Organoselenium Chemistry I; Springer: Heidelberg, 1988; p 1.
2. Ganther, H. E.; Kraus, R. J. Anal. Biochem. 1984, 138, 396.
3. Ganther, H. E.; Kraus, R. J. Methods Enzymol. 1987, 143, 32.
4. Kelly, T. R.; Ghoshal, M. JACS 1985, 107, 3879.
5. Coates, G. E. JCS 1953, 2839.
6. Anderson, J. W.; Barker, G. K.; Drake, J. E.; Rodger, M. JCS(D) 1973, 1716.
7. Jakobs, A.; Christiaens, L.; Renson, M. BSB 1991, 100, 1.
8. Remion, J.; Dumont, W.; Krief, A. TL 1976, 1385.
9. Remion, J.; Krief, A. TL 1976, 3743.
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12. McKillop, A.; Koyuncu, D.; Krief, A.; Dumont, W.; Renier, P.; Trabelsi, M. TL 1990, 31, 5007.
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28. Balenovic, K.; Krizancic, V.; Roglic, G. Bull. Sci. Cons. Acad. Sci. Arts RSF Yougoslavie Sect. A 1973, 18, 227 (CA 1974, 80, 81 982y).
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32. Halazy, S.; Krief, A. TL 1980, 21, 1997.
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38. Krief, A. Top. Curr. Chem. 1987, 135, 1.
39. Van Ende, D.; Cravador, A.; Krief, A. JOM 1979, 177, 1.
40. Barton, D. H. R.; Bridon, D.; Herve, Y.; Potier, P.; Thierry, J.; Zard, S. Z. T 1986, 42, 4983.
41. Paulmier, C. Selenium Reagents And Intermediates In Organic Synthesis; Pergamon: Oxford, 1986, p 1.
42. Hevesi, L. TL 1979, 3025.
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44. Pirson, P.; Christiaens, L. BSF(2) 1973, 704.
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Alain Krief

Facultés Universitaires Notre-Dame de la Paix, Namur, Belgium

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