Acetyl Nitrate1

[591-09-3]  · C2H3NO4  · Acetyl Nitrate  · (MW 105.05)

(nitrating agent for arenes and selected nonaromatics;9-13 can functionalize alkenes to b-nitroacetates;14-17 oxidizes thioethers and disulfides to sulfoxides22)

Physical Data: colorless, mobile liquid; bp 22 °C/70 mmHg,2 2-3 °C/14 mmHg;3 d 1.24 g cm-3.

Solubility: miscible with common organic solvents.

Analysis of Reagent Purity: physicochemical studies indicate a dependence on preparatory method and starting material ratios, as well as age. In commonly used Ac2O/HNO3 mixtures, acetyl nitrate, HOAc, and excess Ac2O are present if the Ac2O/HNO3 ratio is >1; if <1, H2O and even N2O5 can be present.6

Preparative Methods: a typical approach is to add conc Nitric Acid (38 mL) slowly to stirred, cooled Acetic Anhydride (150 mL).7 In the earliest report,2 N2O5 was dissolved in Ac2O; though less practical, this is recommended for preparing anhydrous inorganic nitrates.5 Other methods involve reaction of HNO3 and ketene,3 or AcCl and AgNO3 in MeCN in the presence of the substrate to be nitrated.8

Handling, Storage, and Precautions: unstable and explosive upon heating.2,4 Isolation or distillation is not recommended unless extreme care is taken; freshly prepared solutions should be employed. Controlled thermolysis at ~60 °C leads to N-oxides, tetranitromethane,2 and a yellow oil.5 Highly acidic; avoid skin contact. Reactions should be conducted in a well-ventilated fume hood.

Electrophilic Nitrations.

Solutions of acetyl nitrate behave as NO2+ AcO-, with no sign of acetylation.9 Its synthetic utility is often quite comparable with that of other nitronium reagents, e.g. reaction with toluene gives a mixture of o-, m-, and p-nitrotoluenes in a 60:3:37 ratio at rt,9 and biphenyl yields o- and p-nitro derivatives in a 58:42 ratio (87% yield).10 Naphthalene and pyrene give the corresponding 1-nitro derivatives, while 3-fluoroanthracene and phenanthrene result in nitration at the 9-position.11 Regioselectivity of the nitration reaction can be solvent dependent; in most solvents, reaction with phenanthrene leads to 9-nitrophenanthrene, but in CH2Cl2 or nitrobenzene the 1-nitro isomer dominates.12 Enols can react analogously, as demonstrated with acetoacetate esters (eq 1).13

Addition to Alkenes.

Simple alkenes react with acetyl nitrate to give b-nitroacetates, although nitroalkenes and nitronitrates are often also formed (eq 2).14

Others have found more complex reaction mixtures in this case, and with other cycloalkenes,15 making the synthetic usefulness doubtful; another example concerns methyl-2-furoate.16 Reaction of AcONO2 with 4-methylstilbene yielded the DL-threo derivative (eq 3),17 in line with the nitronium acetate character of the reagent. Cyclic dienes18 also mostly give product mixtures (eq 4).19

Other Applications.

Alcohols can be converted to their nitrates (eq 5),20 and tertiary amines give nitrosamines in fair yields (eq 6).21

Acetyl nitrate reacts rapidly with thioethers and disulfides to give sulfoxides, even at temperatures far below 0 °C; no further oxidation to sulfones occurs, even with an excess of reagent, and yields are near quantitative (eqs 7 and 8).22 With sulfides that are susceptible to Pummerer-type reactions with Ac2O, the use of Benzoyl Nitrate is preferred.

1. (a) FF 1968, 1, 13. (b) Hoggett, J. G.; Moodie, R. B.; Penton, J. R.; Schofield, K. Nitration and Aromatic Reactivity; Cambridge: London, 1971; p 76. (c) Taylor, R. Electrophilic Aromatic Substitution; Wiley: New York, 1990, p 269.
2. Pictet, A.; Khotinsky, E. CB 1907, 40, 1163.
3. Farbw. Hoechst, Ger. Patent 849 405, 1952 (CA 1953, 47, 4899).
4. (a) König, W., AG 1955, 67, 157. (b) Brown, T. A.; Watt, J. A. C. Chem. Br. 1967, 3, 504. (c) Gilbert, E. E. Chem. Eng. News 1980, 58 (40), 5.
5. Chrétien, A.; Boh, G. CR(C) 1945, 220, 822.
6. (a) Chédin, J.; Fénéant, S. CR(C) 1949, 229, 115. (b) Tsvetkov, V. G.; Shmakov, V. A.; Sopin, V. F.; Ivanov, A. V.; Ikonnikov, A. A.; Marchenko, G. N. JGU 1989, 59, 1220.
7. Folsum, H. E.; Castrillón, J. SC 1992, 22, 1799.
8. Olah, G. A.; Lin, H. C.; Olah, J. A.; Narang, S. C. PNA 1978, 75, 1045.
9. Burton, H.; Praill, P. F. G. JCS 1955, 729.
10. Hayashi, E.; Inana, K.; Ishikawa, T. YZ 1959, 79, 972.
11. Velichko, L. I.; Kachurin, O. I.; Balabanov, E. Yu. UKZ 1983, 49, 1293 (CA 1984, 100, 138 725).
12. Velichko, L. I.; Kachurin, O. I.; Balabanov, E. Yu. UKZ 1988, 54, 171 (CA 1989, 110, 38 364).
13. Sifniades, S., JOC 1975, 40, 3562.
14. Bordwell, F. G.; Garbisch, E. W., Jr. JACS 1960, 82, 3588.
15. Borisenko, A. A.; Nikulin, A. V.; Wolfe, S.; Zefirov, N. S.; Zyk, N. V. JACS 1984, 106, 1074.
16. Kolb, V. M.; Darling, S. D.; Koster, D. F.; Meyers, C. Y. JOC 1984, 49, 1636.
17. (a) Drefahl, G.; Crahmer, H. CB 1958, 91, 745; (b) Drefahl, G.; Crahmer, H. CB 1958, 91, 750.
18. Zyk, N. V.; Nikulin, A. V.; Ugrak, B. I.; Borisenko, A. A.; Zefirov, N. S. ZOR 1985, 21, 1189 (CA 1986, 104, 186 032).
19. Liepins, E.; Zolotoyabko, R. M.; Stradins, J.; Trusule, M.; Venters, K. KGS 1980, 741 (CA 1980, 93, 220 008).
20. Bonner, T. G. JCS 1959, 3908.
21. Boyer, J. H.; Pillai, T. P.; Ramakrishnan, V. T. S 1985, 677.
22. Louw, R.; Vermeeren, H. P. W.; van Asten, J. J. A.; Ultée, W. J. CC 1976, 496.

Robert Louw

Leiden University, The Netherlands

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.