Silver(I) Nitrate

AgNO3

[7761-88-8]  · AgNO3  · Silver(I) Nitrate  · (MW 169.88)

(mild oxidizing agent and Lewis acid used in a wide variety of chemical reactions)

Physical Data: mp 212 °C; d 4.352 g cm-3.

Solubility: sol H2O, MeCN, alcohol, acetonitrile, DMF.

Form Supplied in: white crystalline solid; widely available.

Handling, Storage, and Precautions: mild oxidizing agent; may be fatal if inhaled or swallowed.

Deprotection.

Silver nitrate is used as a deprotecting agent for a number of functional groups. Thus S-trityl ethers are readily cleaved (AgNO3/Pyridine, 5 min, rt)1a to the thiol silver salts which are converted to the thiols on treatment with Hydrogen Sulfide. The method has been applied to S-trityl ethers in nucleoside,1a peptide,1b and b-lactam1c chemistry, although it is not always successful.2 Selective cleavage of an S,S-diaryl phosphorodithioate in the presence of an O-dimethoxytrityl group occurs using a large excess of AgNO3 (eq 1).3 Other deprotecting agents such as NaIO4, H2O2, and NCS are unsuccessful in this process.3

Thioacetals,4 1,3-dithianes,5 and 1,3-oxathianes6 are converted, on treatment with AgNO3/N-Chlorosuccinimide (or N-Bromosuccinimide), to the corresponding ketones. The method is specially useful when sensitive 1,4-unsaturated diones are being liberated.5b Cyanuric acid can be used in place of NCS for the particularly difficult task of converting a diphenyl thioacetal to its ketone derivative.7 Benzothiazoles are readily converted, via their 2-lithio derivatives, to a variety of intermediates.8 Treatment of these derivatized benzothiazoles with Iodomethane followed by Sodium Borohydride gives the corresponding N-methylbenzothiazolines, which are readily cleaved with AgNO3 in methanol to the corresponding aldehydes in high yields. This is a useful high yielding procedure for the preparation of a,b-unsaturated aldehydes.8 Cleavage of O-methylethoxymethoxy ethers (OMEM ethers) in the presence of a dithiane is accomplished by converting the OMEM ether to the O-isopropylthiomethyl ether, which is then cleaved to the desired alcohol with AgNO3 in the presence of 2,6-Lutidine.9 AgNO3 has also been used for the hydrolysis of enol thioethers,10 tetrahydropyranylthio ethers,11 S-t-butyl esters,12 and thiobenzoates,12 to the respective alcohols, for the conversion of dithiobenzoates to S-benzoates,13 thioamides to amides,14 thioureas to ureas,15 and for the conversion of orthothioesters to orthoesters.16

Protection.

Reaction rates for the conversion of the primary OH groups of nucleosides to the protected O-trityl ethers with 4,4,4-tris(4,5-dichlorophthalimido)trityl bromide are considerably enhanced by the addition of AgNO3.17 AgNO3 is also used for the selective preparation of primary t-butyldimethylsilyl ethers by the reaction of nucleosides with t-Butyldimethylchlorosilane in MeCN.18 Yields in both reactions are high. AgNO3 is an effective agent for the conversion of several glucopyranoses to their 1,2-orthoacetates19 and as an agent for the formation of glycosides20 (see also Silver(I) Nitrite).

Ring Expansions, Contractions, and Rearrangements.

AgNO3-promoted rearrangements occur in numerous instances; a few examples are given. Thus the 4-cyano-4,5-dihydroazepine in eq 2 gives the furo[2,3-b]pyridine on heating with an aqueous solution of AgNO3.21 Treatment of the N-chloroenolamine in eq 3 with a threefold excess of AgNO3 gives the b-lactam; yields are about 50%, depending on the substituent used.22 The 1,1-bishomocubane in eq 4, on treatment with AgNO3 in aqueous methanol, rearranges to the pentacycle in quantitative yield.23

Dehalogenations.

AgNO3 has been widely used for solvolysis with concomitant rearrangement of dihalocyclopropanes. Thus the trichlorocyclopropa[c]chromene in eq 5 gives the (dichloromethylene)chroman-4-one in 93% yield.24 Many other examples are known. Dehydrobromination of the bromotetralone in eq 6 with AgNO3 gives exclusively the endocyclic unsaturated ketone in 90% yield; other reagents for this reaction give mixtures of the exo- and endocyclic alkenes.25

Solvolysis of arylmethyl halides with AgNO3 in hot aqueous ethanol gives the corresponding alcohols,26 whereas a similar reaction on alkyl bromides in MeCN is reported to be an excellent procedure for the preparation of pure nitrate esters.27 Benzyl dibromides are converted to the corresponding aldehydes in high yields,28 and a-bromo ketones give high yields (>80%) of the corresponding a-diketones on treatment with AgNO3 in MeCN.29

Cycloadditions.

The electrophilic nature of AgNO3 enables it to complex with alkynes and allenes, thus enabling intramolecular cycloadditions to proceed. For example, treatment of a series of phenolic keto-ynes (eq 7) with a catalytic amount of AgNO3 in methanol promotes cycloaddition to the triple bond in high yield.30 Similarly, a-hydroxyallenes are rapidly converted to 2,5-dihydropyrans on treatment with AgNO3/CaCO3 in aq acetone (eq 8).31

On extending the hydroxy alkyl chain from the allenic group by two or three carbon atoms, cyclization results in the formation of the corresponding a-vinyltetrahydrofuran32 or a-vinyltetrahydropyran,33 respectively, both in high yields. In a similar manner, treatment of a-, g- and d-aminoallenes with AgNO3 in aqueous acetone gives the corresponding 2,3-dihydropyrroles,34 a-vinylpyrrolidines,35 and a-vinylpiperidines,35 respectively, in good yields.

Oxidative Couplings.

Alkylboranes, formed on reaction of terminal alkenes with diborane, dimerize on treatment with an aqueous solution of AgNO3/NaOH. Thus hexene gives a 66% yield of dodecane,36 and the dienes 1,5-hexadiene and geranyl acetate are converted to cyclohexane (66%) and trans-p-menthane (85%).37 Although the use of AgNO3/NaOH for these coupling reactions is, to all accounts, equivalent to the use of Silver(I) Oxide, oxidative cyclization is reported to be less successful when this latter reagent is used. Oxidative dimerization of the dianions of a,b-unsaturated carboxylic acids with AgNO3/THF gives moderate yields of the dienedioic acids, but the use of Iodine for this coupling gives higher yields (40-80%).38

Coverage of the use of AgNO3/NaOH for oxidation of alcohols, aldehydes, etc., has not been included in this section as this ostensively amounts to the use of Silver(I) Oxide.

Related Reagents.

Zinc-Copper(II) Acetate-Silver Nitrate.


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2. Hiskey, R. G.; Harpold, M. A. JOC 1968, 33, 559.
3. Sekine, M.; Hamaoki, K.; Hata, T. JOC 1979, 44, 2325.
4. Geiss, K.; Sevring, B.; Pieter, R.; Seebach, D. AG(E) 1974, 13, 479.
5. (a) Corey, E. J.; Erickson, B. W. JOC 1971, 36, 3553. (b) Corey, E. J.; Grouse, D. JOC 1968, 33, 298.
6. Frye, S. V.; Eliel, E. L. TL 1985, 26, 3907.
7. Cohen, T.; Nolan, S. M. TL 1978, 3533.
8. Corey, E. J.; Boger, D. L. TL 1978, 5; 1978, 13.
9. Corey, E. J.; Weigel, L. O.; Chamberlin, R.; Cho, H.; Hua, D. H. JACS 1980, 102, 6613.
10. Kejian, C.; Sanner, M. A.; Carlson, R. M. SC 1990, 20, 901.
11. Kruse, C. G.; Poels, E. K.; Jonkers, F. L.; van der Gem, A. JOC 1978, 43, 3548.
12. Shenvi, A. B.; Gerlach, H. HCA 1980, 63, 2426.
13. Hedgley, E. J.; Leon, N. H. JCS(C) 1970, 467.
14. Barrett, C. G. JCS 1965, 2825.
15. Mechoulam, R.; Sondheimer, F.; Melera, A. JACS 1961, 83, 2022.
16. Breslow, R.; Pandey, P. S. JOC 1980, 45, 740.
17. (a) Sekine, M.; Hata, T. JACS 1984, 106, 5763. (b) Sekine, M.; Hata, T. JACS 1986, 108, 4586.
18. Hakimelahi, G. H.; Proba, Z. A.; Ogilvie, K. K. TL 1981, 22, 4775.
19. Tsui, D. S. K.; Gorin, P. A. J. Carbohydr. Res. 1985, 144, 137.
20. Nashed, E. M.; Glaudemans, C. P. J. JOC 1987, 52, 5255.
21. Bullock, E.; Gregory, B.; Johnson, A. W. JCS 1964, 1632.
22. Wasserman, H. H.; Adickes, H. W.; de Ochoa, O. E. JACS 1971, 93, 5586.
23. Dauben, W. G.; Buzzolini, M. G.; Schallhorm, C. H.; Whalen, D. L.; Palmer, K, J. TL 1970, 787.
24. Brown, P. E.; Islam, Q. TL 1987, 28, 3047.
25. Cromwell, N. H.; Ayer, R. P.; Foster, P. W. JACS 1960, 82, 130.
26. Aldous, D. L.; Riebsomer, J. L.; Castle, R. N. JOC 1960, 25, 1151.
27. Ferris, A. F.; McLean, K. W.; Marks, I. G.; Emmons, W. D. JACS 1953, 75, 4078.
28. Buggy, T.; Ellis, G. P. JCR(S) 1980, 159.
29. Kornblum, N.; Frazier, H. W. JACS 1966, 88, 865.
30. Jong, T-T.; Leu, S-J. JCS(P1) 1990, 423.
31. Marshall, J. A.; Wang, X. J. JOC 1990, 55, 2995.
32. Gore, J.; Audin, P.; Dootheau, A.; Ruest. L. BSF 1981, 313.
33. Gallagher, T. CC 1984, 1554.
34. Arseniyadis, S.; Gore, J. TL 1983, 24, 3997.
35. Arseniyadis, S.; Sartoretti, J. TL 1985, 26, 729.
36. Brown, H. C.; Hebert, N. C.; Snyder, C. H. JACS 1961, 83, 1002.
37. Murphy, R.; Prager, R. H. TL 1976, 463.
38. Aurell, M. J.; Gil, A.; Tortajada, A.; Mestres, R. S 1990, 317.

Duncan R. Rae

Organon Laboratories, Motherwell, UK



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