NO Photochemical Release from Diazeniumdiolates
A R T I C L E S
temperature over 24 h. Diethyl ether (20 mL) was then added; the
sodium bromide was removed by gravity filtration, diethyl ether and
tetrahydrofuran were removed by rotary evaporation, and DMF was
removed under vacuum. The resulting yellow oil was dissolved in
dichloromethane and washed with water. The organic layer was dried
over magnesium sulfate and concentrated by rotary evaporation to yield
the desired product, which was purified on a silica column using
dichloromethane as the eluent.
(300 MHz, CDCl3) δ 1.07 (t, 6H, J ) 8 Hz), 2.97 (s, 6H), 3.06 (q, 4H,
J ) 8 Hz), 5.24 (s, 2H), 6.67-6.75 (m, 3H), 7.18-7.26 (m, 1H); 13C
NMR (400 MHz, CDCl3) δ 11.6, 40.69, 48.86, 76.4, 112.46, 112.82,
116.73, 129.28, 136.61, 150.85; MS (FAB) m/z (rel intens) 289 (M +
Na, 100), 265 (M - H, 5); UV-vis (CH3CN) λmax 306 nm (ꢀ ) 3058
M-1 cm-1).
Data for O2-(3,5-bis(dimethylamino)benzyl)-1-(N,N-diethylami-
no)diazen-1-ium-1,2-diolate (8): 20% yield as a yellow oil; 1H NMR
(300 MHz, CDCl3) δ 1.05 (t, 6H, J ) 8 Hz), 2.96 (s, 12H), 3.07 (q,
4H, J ) 8 Hz), 5.20 (s, 2H), 6.02-6.03 (s, 1H), 6.19-6.20 (s, 2H);
13C NMR (400 MHz, CDCl3) δ 11.81, 41.03, 48.95, 77.235, 97.78,
102.53, 137.24, 152.01; MS (FAB) m/z (rel intens) 332 (M + Na, 82),
309 (M+, 20); UV-vis (CH3CN) λmax 317 nm (ꢀ ) 3704 M-1 cm-1).
O2-(3,5-Dihydroxybenzyl)-1-(N,N-diethylamino)diazen-1-ium-1,2-
diolate (9). The commercially available 3,5-dihydroxybenzoic acid was
esterified in quantitative yield to afford the corresponding methyl ester.39
The phenolic hydroxy groups were converted to methoxymethyloxy
functionalities.40 Lithium aluminum hydride reduction gave the alco-
hol,39 which was brominated under nonacidic conditions.34 The bromide
was coupled with 15 as described above in high yield, and the
methoxymethyloxy groups were removed using aqueous acid to afford
9 in quantitative yield: 1H NMR (300 MHz, CDCl3), δ 1.15 (s, 6H, J
) 7 Hz), 3.09 (q, 4H, J ) 7 Hz), 5.12 (s, 2H), 6.30 (t, 1H, J ) 2 Hz),
6.44 (d, 2H, J ) 2 Hz), 6.80 (s br, 2H).
Data for O2-(3-methoxybenzyl)-1-(N,N-diethylamino)diazen-1-
1
ium-1,2-diolate (5): 80% yield as a yellow oil; H NMR (300 MHz,
CDCl3) δ 1.05 (t, 6H, J ) 8 Hz), 3.07 (q, 4H, J ) 8 Hz), 3.82 (s, 3H),
5.25 (s, 2H), 6.86-6.88 (d, 1H, J ) 8.5 Hz), 6.93-6.99 (m, 2H), 7.23-
7.28 (m, 1H); 13C NMR (400 MHz, CDCl3) δ 11.64, 48.89, 55.39,
75.71, 113.62, 114.56, 128.81, 129.71, 137.38, 159.86; MS (FAB) m/z
(rel intens) 276 (M + Na, 100), 254 (M + H, 3); UV-vis (CH3CN)
λmax 273 nm (ꢀ ) 3555 M-1 cm-1).
Data for O2-(3,5-dimethoxybenzyl)-1-(N,N-diethylamino)diazen-
1-ium-1,2-diolate (6): 90% yield as a yellow oil; 1H NMR (300 MHz,
CDCl3) δ 1.05 (t, 6H, J ) 7 Hz), 3.05 (q, 4H, J ) 7 Hz), 3.80 (s, 6H),
5.27 (s, 2H), 6.41 (t, 1H), 6.53 (d, 2H).
Preparation of O2-(3-(Dimethylamino)benzyl)- and O2-(3,5-Bis-
(dimethylamino)benzyl)-1-(N,N-diethylamino)diazen-1-ium-1,2-di-
olate (7, 8). The methyl esters of the commercially available 3-amino-
and 3,5-diaminobenzoic acids were prepared according to literature
procedures.36 Each amino group was then methylated to the corre-
sponding trimethylammonium salt using a 5-fold excess of methyl
iodide.37 Reduction of the ammonium salts with a large excess of lithium
aluminum hydride38 gave the desired 3-(dimethylamino)- and 3,5-bis-
(dimethylamino)benzyl alcohols, respectively, in 80% yield. The
bromide precursors were prepared by reacting the corresponding benzyl
alcohols with bromide ion.34 These bromides were too reactive to be
isolated and were coupled immediately with diazeniumdiolate 15 to
afford 7 and 8 in yields of ca. 20%.
Preparation of Authentic Samples for Product Analysis. The
required benzaldehyde41 and oxime42 derivatives were synthesized (from
the corresponding benzyl alcohols) according to literature procedures.
Acknowledgment. J.P.T. gratefully acknowledges the Na-
tional Institutes of Health (Grant R01 GM58109) for generous
support of this research. A Camille Dreyfus Teacher-Scholar
Award and an Alfred P. Sloan Research Fellowship also support
this research.
Data for O2-(3-(dimethylamino)benzyl)-1-(N,N-diethylamino)-
Supporting Information Available: Quantification of the
amount of NO formed following thermal dissociation of varying
concentrations of diazeniumdiolate 15 (PDF). This material is
1
diazen-1-ium-1,2-diolate (7): 30% yield as a yellow oil; H NMR
(36) (a) Methyl 3-aminobenzoate: Elhadi, F. E., Ollis, W. D., Stoddart, J. F. J.
Chem. Soc., Perkin Trans. 1 1982, 8, 1727-1730. (b) Methyl 3,5-
diaminobenzoate: Kraft, A.; Osterod, F. J. Chem. Soc., Perkin Trans. 1
1998, 6, 1019-1025.
(37) Drewes, S. E.; Magojo, H. E. M.; Sutton, D. A. J. Chem. Soc., Perkin
Trans. 1 1975, 13, 1283-1284.
(38) (a) 3-(Dimethylamino)benzyl alcohol: Sakurai, H.; Izuoka, A.; Sugawara,
T. J. Am. Chem. Soc. 2000, 122, 9723-9734. (b) 3,5-Bis(dimethylamino)-
benzyl alcohol: Connolly, C. J. C.; Hamby, J. M.; Schroeder, M. C.;
Barvian, M.; Lu G. H.; Paneck, R. L.; Amar, A.; Shen, C.; Kraker, A. J.;
Fry, D. W.; Klohs, W. D.; Doherty, A. M. Biol. Org. Med. Chem. Lett.
1997, 7, 2415-2420.
JA026900S
(39) Stewart, G. M.; Fox, M. A. J. Am. Chem. Soc. 1996, 118, 4354-4360.
(40) Duffley, R. P.; Handrick, G. R.; Uliss, D. B.; Lambert, G.; Dalzell, H. C.;
Razdan, R. K. Synthesis 1980, 9, 733-736.
(41) Sakurai, H.; Izuoka, A.; Sugawara, T. J. Am. Chem. Soc. 2000, 122, 9723-
9734.
(42) Gale, D. J.; Wilshire, J. F. K. Aust. J. Chem. 1975, 28, 2447-2458.
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J. AM. CHEM. SOC. VOL. 124, NO. 33, 2002 9811