Triphenyl Phosphite1


[101-02-0]  · C18H15O3P  · Triphenyl Phosphite  · (MW 310.30)

(mildly nucleophilic phosphite for converting alcohols to alkyl halides;3 coupling agent in peptide and related syntheses,1b,12 as its ozone adduct, a low-temperature source of singlet oxygen1b)

Physical Data: mp 22-25 °C; bp 360 °C, 180-189 °C/1 mmHg; n25D 1.5890; d 31P 125-129.

Solubility: insol H2O (hydrolyzes to (PhO)2P(O)H); miscible most organic solvents; alcoholic solvents may transesterify.

Form Supplied in: colorless liquid, 97% pure, widely available, showing only one peak in 31P NMR. The balance is largely phenol.

Purification: an ethereal solution is washed with aqueous alkali, dried, and distilled.

Handling, Storage, and Precautions: fairly safe to handle, but it is a skin sensitizer and will usually contain phenol.

General Discussion.

The ester converts alcohols to alkyl halides in the presence of a hydrogen halide, a halogen, or another alkyl halide (eqs 1 and 2), the two last being mild and convenient procedures.2,3 Good yields are obtained, even with neopentyl halides, and the reaction proceeds with inversion at carbon.4 The intermediate phosphonium salts may be prepared independently but are very susceptible to hydrolysis and are conveniently generated and used as required. Methyltriphenoxyphosphonium iodide has also found use in the deoxygenation of epoxides5 (with retention of stereochemistry) and the dehydration of secondary alcohols.6 Phenyl esters of carboxylic acids can be made from the salts and a carboxylate ion7 or from the free acid and the neutral ester8 (eqs 3 and 4). Phosphorus9 and sulfur10 acids may be esterified similarly.

The adduct of (PhO)3P and Ozone,1b apparently a cyclic phosphorane (d 31P -63), is stable below -35 °C and on warming liberates oxygen. It functions in many ways as a convenient low-temperature source of singlet oxygen (eq 5),11 though there are some significant differences and it functions similarly at temperatures as low as -70 °C where the adduct is quite stable.

In the presence of bases, particularly Imidazole, (PhO)3P acts either alone12 or with 2,2-Dipyridyl Disulfide13 as a coupling agent for peptide synthesis (eq 6) with very little if any racemization. With 2,2-Dipyridyl Diselenide, it has found use in the preparation of nucleoside phosphoranilidates14 and oligonucleotides.15 The ester has been occasionally used as a mild deoxygenation agent (eq 5), and in the cyclization of 2-acylaminobenzoic acids to the corresponding 4H-3,1-benzoxazin-4-ones.16 It is a convenient reagent for purifying Thionyl Chloride.17

Related Reagents.

Bromine-Triphenyl Phosphite.

1. (a) Gerrard, W.; Hudson, H. R. Organic Compounds of Phosphorus; Kosolapoff, G. M.; Maier, L., Eds.; Wiley: New York, 1973; Vol. 5, p 21. (b) Organophosphorus Reagents in Organic Synthesis; Cadogan, J. I. G., Ed.; Academic: London, 1979.
2. Landauer, S. R.; Rydon, H. N. JCS 1953, 2224.
3. (a) Coe, D. G.; Landauer, S. R.; Rydon, H. N. JCS 1954, 2281. (b) Black, D. K.; Landor, S. R.; Patel, A. N.; Whiter, P. F. TL 1963, 483.
4. Verheyden, J. P. H.; Moffat, J. G. JOC 1970, 35, 2319.
5. Yamada, K.; Goto, S.; Nagase, H.; Kyotani, Y.; Hirata, Y. JOC 1978, 43, 2076.
6. Spangler, C. W.; Hartford, T. W. S 1976, 108.
7. Hudson, R. F.; Chopard, P. A. HCA 1962, 45, 1137.
8. Iselin, B.; Rittel, W.; Sieber, P.; Schwytzer, R. HCA 1957, 40, 374.
9. Markowska, A.; Olejnik, J.; Mlotkowska, B.; Sobanska, M. PS 1981, 10, 143.
10. Rafik, K.; Leader, H.; Goldblum, A.; Poreuer, E. CI(L) 1987, 857.
11. Foster, C. H.; Berchtold, G. A. JOC 1975, 40, 3743.
12. (a) Mitin, V. V.; Glinskaya, O. V. TL 1969, 5267. (b) Stelzel, P. MOC 1974, 15/2, 2.46.
13. Veki, M.; Takushi, S.; Hayashida, A.; Mukayama, T. CL 1973, 733.
14. Takaku, H.; Yamazaki, T. Nucleic Acid Chem. 1978, 2, 869.
15. Takaku, H.; Shimida, Y.; Nakazima, Y.; Hata, T. Nucleic Acids Res. 1976, 3, 1233.
16. Rabilloud, G.; Sillion, B. JHC 1980, 17, 1065.
17. Friedman, L.; Wetter, W. P. JCS(A) 1967, 36.

Michael J. Gallagher

University of New South Wales, Kensington, NSW, Australia

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