The First Conversion of Primary Alkyl Halides to Nitroalkanes under Aqueous Medium Roberto Ballini,* Luciano Barboni, and Guido Giarlo Dipartimento di Scienze Chimiche dell’Universita ` di Camerino, Via S. Agostino 1, 62032 Camerino, Italy roberto.ballini@unicam.it Received June 7, 2004 Abstract: Primary nitroalkanes and R,ω-dinitroalkanes can be easily obtained in aqueous medium by reaction of the corresponding halo derivatives with silver nitrite. The procedure works well with both alkyl bomide and alkyl iodide and proceeds in satisfactory to good yields even in the presence of other functionalities, minimizing the forma- tion of the undesired alkyl nitrites. Nitroalkanes are one of the fundamental classes of substances in organic chemistry. 1 Historically, they have been important as explosives and precursors for azo dyes. 2 Today, they play a key role as synthetic intermedi- ates or targets in the preparation of dyes, plastics, perfumes, pharmaceuticals and many natural products. 3 This is primarily due to the fact that the nitroalkanes undergo a variety of carbon-carbon bond-forming pro- cesses, and the nitro group can be converted into several other functional groups. 4 Thus, an easy and convenient availability of the aliphatic nitro compounds is crucial. These molecules can be obtained (i) by direct nitration of aliphatic hydrocarbons under certain conditions, ac- tivated hydrocarbons via anionic intermediates, alkenes, and ketones (R-nitration), 4e,5 (ii) by conversion of other functionalities to the nitro group (carbonyls, oximes, azides, etc.), 3a,4c,6 and (iii) by nitration of the alkyl halides with metal nitrites. For the latter method, silver nitrite in diethyl ether (Victor-Meyer reaction), potassium nitrite, or sodium nitrite in N,N-dimethylformamide (DMF) or in dimethyl sulfoxide (DMSO) (Kornblum reaction) have been frequently used. 7,8 The conversion of alkyl halides to nitro compounds is one of the most used methods for the preparation of nitroalkanes; any way, long-reaction times, the use of toxic solvents, and tedious workup are demanded and/or low yields are obtained. Moreover, a further and serious drawback is that the obtained products are usually a mixture, difficult to purify, of the desired nitroalkanes together with the undesired alkyl nitrites. Increasingly demanding environmental legislation, public and corporate pressure, and the resulting drive toward clean technology in the chemical industry, with emphasis on reduction of waste at the source, will require increasing attention on the use of less toxic and environ- mentally compatible materials in the design of new syn- thetic methods. 9 Recently, there has been increasing recognition that organic reactions carried out in water may offer advantages over those occurring in organic sol- vents because water is cheap and safe, it allows a precise control of the reactivity, and/or the selectivity of the reaction can be dramatically influenced when carried out in water. 10 With the aim to develop more efficient pro- cesses and in continuation with our studies devoted to the chemistry of aliphatic nitro compounds, 4c,11 we have now found the first methodology for the title conversion in aqueous medium. In fact, treatment of primary alkyl hal- ides 1 with 4 equiv of silver nitrite at room temperature or 60 °C (Scheme 1) allows satisfactory to good yields (53-90%, Table 1) of a variety of primary nitroalkanes 2, mainly in very short reaction times (0.5-1.25 h). The reason for using 4 equiv of silver nitrite is that in these conditions the reaction is fast enough to minimize the competitive formation of the corresponding alcohol. Although our method works well with both alkyl bromides and alkyl iodides, the latter often show a higher reactivity (e.g., 1g vs 1a, 1g vs 1c, and 1j vs 1d). Furthermore, other functionalities such as carbon- carbon double bonds, ester, imide, and ketone are pre- served under our mild reaction conditions. Of particular interest is the possibility to perform the one-pot trans- (1) (a) Mu ¨ ller, E., Ed. Houben-Weyl: Methoden der Organischen Chemie; Thieme: Stuttgart, 1971; Vol. 10/1. (b) Mu ¨ ller, E., Ed. Houben- Weyl: Methoden der Organischen Chemie; Thieme: Stuttgart, 1992; Vol. E16D/1. (c) Feuer, H., Ed. The Chemistry of the Nitro and Nitroso Group; Wiley-Interscience: New York, 1969, Part 1, 1970; Part 2, 1982, supplement F. (2) See for example: (a) Wade, P. A.; Kondracki, P. A.; Carrol, P. J. J. Am. Chem. Soc. 1991, 113, 8807-8811. (b) Marchand, A. P.; Rajagopal, D.; Bott, S. G. J. Org. Chem. 1994, 59, 5499-5501. (3) (a) Ono, N. The Nitro Group in Organic Synthesis; Wiley-VCH: New York, 2001. (b) Feuer, H.; Nielson, A. T. Nitro Compounds: Recent Advances in Synthesis and Chemistry; VCH: New York, 1990. (c) Torssell, K. B. G. Nitrile Oxides, Nitrones, and Nitronates in Organic Synthesis; VCH: New York, 1988. (d) Ballini, R. In Studies in Natural Products Chemistry; Atta-ur-Rahman, Ed.; Elsevier: Amsterdam, 1997; Vol. 19, pp 117-184. (4) (a) Barret, A. G. M.; Graboski, G. G. Chem. Rev. 1986, 86, 751- 762. (b) Varma, R. S.; Kabalka, G. W. Heterocycles 1986, 24, 2645- 2677. (c) Rosini, G.; Ballini, R. Synthesis 1988, 833-847. (d) Ballini, R.; Petrini, M. Tetrahedron 2004, 60, 1017-1047. (5) Olah, G. A.; Malhotra, R.; Narang, S. C. Nitration: Methods and Mechanisms; VCH: New York, 1990. (6) Seebach, D.; Colvin, E. W.; Lehr, F.; Weller, T. Chimia 1979, 33,1-18. (7) (a) Kornblum, N. Org. React. 1962, 12, 101. (b) Feuer, H.; Leston, G. Organic Syntheses; Wiley: New York, 1963; Collect. Vol. 4, p 368. (8) An alternative method with pre-prepared anion-exchange resins, in benzene, has been also reported: Gelbard, G.; Colonna, S. Synthesis 1977, 113-116. (9) (a) Amato, J. Science 1993, 259, 1538-1541. (b) Ilman, D. L. Chem. Eng. News 1993, 71,5-6. (c) Ilman, D. L. Chem. Eng. News 1994, 72, 22-27. (10) (a) Grieco, P. A. Organic Synthesis in Water; Blackie Academic and Professional: London, 1998. (b) Li, C. J.; Chan, T. H. Organic Reactions in Aqueous Media; John Wiley and Sons: New York, 1997. (c) Lubineau, A. Chem. Ind. 1996, 123. (d) Fringuelli, F.; Piermatti, O.; Pizzo, F. In Target in Heterocycles Systems, Chemistry and Properties; Attanasi, O., Spinelli, D., Eds.; Italian Society of Chemistry: Rome, 1997; Vol. 1, p 57. (e) Li, C. J. Chem. Rev. 1993, 93, 2023-2035. (11) (a) Rosini, G.; Ballini, R.; Petrini, M.; Marotta, E.; Righi, P. Org. Prep. Proc. Int. 1990, 22, 707-746. (b) Ballini, R.; Bosica, G. Recent Research Development in Organic Chemistry; Transworld Research Network: Trivandrum, 1997; Vol. 1, pp 11-24. (c) Ballini, R. Synlett 1999, 1009-1018. SCHEME 1 10.1021/jo049048b CCC: $27.50 © 2004 American Chemical Society J. Org. Chem. 2004, 69, 6907-6908 6907 Published on Web 09/04/2004