Cyclic R-Acetoxynitrosamines
J. Am. Chem. Soc., Vol. 121, No. 22, 1999 5163
chloride/ether in the cases of 12 and 13. The compound 14 was similarly
purified using methylene chloride as eluant. 12: 1H NMR (CD3CN) δ
10.00 (1H, s), 6.22 (1H, m), 3.50 (2H, m), 2.10 (4H, m) ppm; 13C
NMR (CD3CN) δ 95.03, 45.18, 29.14, 20.97 ppm. Anal. Calcd: C,
36.36; H, 6.10; N, 21.20. Obsd: C, 36.56; H, 6.14; N, 21.04. 13: 1H
NMR (CDCl3) δ 8.32 (1H, s), 6.25 (1H, t), 4.85 (1H, q), 2.75 (1H, m),
2.25 (1H, m), 1.8 (5H, m) ppm; 13C NMR (CDCl3) δ 91.84, 36.10,
28.15, 23.69, 18.94 ppm. Anal. Calcd: C, 41.09; H, 6.90; N, 19.17.
Obsd: C, 41.34; H, 6.85; N, 18.89. 14: 1H NMR (CDCl3) δ 8.53 (1H,
b), 3.69 (2H, m), 2.46 (1H, m), 2.07 (3H, m), 1.99 (3H, s) ppm; 13C
NMR (CDCl3) δ 101.44, 47.94, 37.83, 23.39, 21.16 ppm.
r-Hydroxynitrosamines. In a NMR tube, the R-hydroperoxy
compound was converted to the R-hydroxy compound by addition of
triphenylphosphine in 0.7 mL of CDCL3 or CD3CN. Conversion
occurred within the time required to shake the tube, shim the instrument,
and record the spectrum. 8:1H NMR (CD3CN) δ 6.10 (1H, t), 4.88
(OH, d), 3.50 (2H, m), 2.10 (4H, m) ppm; 13C NMR (CD3CN) δ 84.60,
44.89, 33.03, 20.49 ppm. 9: 1H NMR (CDCl3) δ 6.22 (1H, b), 4.75-
(1H, q), 4.60 (OH, b), 2.80 (1H, m), 2.00 (6H, m) ppm; 13C NMR
(CDCl3) δ 81.62, 35.77, 31.66, 24.12, 18.23 ppm. 10: 1H NMR (CDCl3)
δ 3.49 (1H, t), 2.59 (2H, m), 2.37 (1H, m), 2.16 (3H, s), 1.95 (2H, m)
ppm.
Figure 1. Plot of the log of ko, the buffer independent rate constant,
against pH for the decay of cyclic R-acetoxynitrosamines 6 (solid
circles) and 7 (squares) and cyclic R-hydroxynitosamines 8 (triangles),
9 (diamonds), and 10 (inverted triangles) at 25 °C ionic strength 1M
(NaClO4). Open circles are for 9 derived from the decay kinetics of 7
(see text).
2,4-Dinitrophenyl Hydrazones 15, 16, and 17.18 To a solution of
0.2 g of 2,4-dinitrophenylhydrazine in 50 mL of HCl (2N) at 60 °C
was added 0.1 g of 2,3-dihydrofuran, 3,4-dihydro-2H-pyran or cro-
tonaldehyde to generate 15, 16, and 17, respectively. The solution was
cooled at 0 °C for 30 min and filtered. The yellow solid was washed
with HCl (2 N) and purified by recrystallization in EtOH. 15:1H NMR
(CDCl3) δ 11.20 (1H, b), 9.10(1H, d), 8.30 (1H, q), 7.90 (1H, d), 7.60
(1H, t), 3.80 (2H, t), 2.60 (2H, m), 1.95 (2H, m), 1.55 (1H, b) ppm.
16: 1H NMR (CDCl3) δ 11.10 (1H, b), 9.20 (1H, d), 8.30 (1H, q),
8.00 (1H, d), 7.60 (1H, t), 3.80 (2H, t), 2.55 (2H, m), 1.8 (4H, m),
1.30 (1H, t) ppm. 17: 1H NMR (CDCl3) δ 11.10 (1H, b), 9.12(1H, d),
8.33 (1H, q), 8.27 (1H, d), 7.97 (1H, d), 7.75 (1H, d), 6.31 (2H, m),
1.96 (3H, d) ppm; 13C NMR (CDCl3) δ 150.06, 144.79, 140.81, 138.81,
129.93, 128.5, 127.83, 123.49, 116.59, 18.84 ppm.
r-Azido-N-nitrosopyrrolidine, 18. R-Acetoxy-N-nitrosopyrrolidine
(0.16 g) was added to 10 mL of water containing 0.65 g of NaN3 and
0.146 g of cacodyllic acid, and the reaction was gently stirred for 40
h at room temperature. The reaction was extracted into ether and dried
with Na2SO4. Final purification was carried out by column chroma-
tography using silica gel and CH2Cl2 as eluant. Yield: 30%. 1H NMR
(CDCl3): E(87%) 6.25 (b, 1H); 3.4-3.8 (d of m, 2H); 1.95-2.2 (m,
4H). Z(13%) 5.71 (b,1H); 4.35 (m, 2H); 1.95-2.2 (m). Anal. Calcd:
C, 34.04; H, 5.00; N, 49.62. Obsd: C, 34.32; H, 5.00; N, 49.36.
r-Azido-N-nitrosopiperidine, 19. This was isolated using a prod-
cedure analogous to that above for the pyrrolidine compound from 0.035
g of the corresponding R-acetoxy compound. The purified material
(preparative TLC) migrated as a single spot on TLC and was >97%
pure on HPLC analysis monitoring at 230 nm. 1H NMR (CDCl3): 6.45
(s, 1H), 2.93 (t of d, 2H), 2.05 (m, 2H); 1.70-1.90 (m, 4H).
Figure 2. Plot of absorbance at 230 nm versus time for the decay of
7 at pH 5.2, 0.02 M acetate buffer 25 °C, ionic strength 1 M (NaClO4).
Solid line is a best fit to eq 14.
cation). The value of kobsd in 0.15 M buffer solution increased
104% above ko. The change in ko as a function of pH is indicated
in Figure 1.
In the case of R-acetoxynitrosopiperidine, below pH 6, the
kinetics of decay were not first order, as typified by the
absorbance versus time plot in Figure 2. Such behavior was
reminiscent of our earlier observation that some acyloxydialky-
lnitrosamines have a reactivity comparable with the product
R-hydroxydialkylnitrosamine so that the latter is formed as a
non-steady-state intermediate.6b Treatment of these data is
explained in the Discussion section.
Results
r-Acetoxynitrosamines. In the case of R-acetoxynitrosopy-
rrolidine, 6, at all values of pH, and R-acetoxynitrosopyrrolidine,
7, above pH ) 6, the kinetics of decay of the N-NO
chromophore exhibited good first-order behavior for 3-5 half-
lives of reaction. The values of kobsd varied only slightly with
buffer concentration at constant buffer ratio, typically changing
less than 10% over a change in concentration that ranged
between 0.03 and 0.3 M. Plots of kobsd versus buffer concentra-
tion, usually containing three points, were extrapolated to zero
buffer concentration and the corresponding rate constant was
taken as ko, the buffer-independent rate constant. The largest
effect of buffer concentration was observed with the reaction
R-acetoxynitrosopyrrolidine in hydrazine buffer (80% mono-
Activation parameters for the decay of the cyclic R-acetox-
ynitrosamines 6 and 7 were obtained from measurements of
kobsd in 0.05 M cacodylic acid buffers containing 50% buffer
base form. The decay curves in all cases exhibited clean first-
order behavior over 5 half-times of reaction. At 25 °C, plots of
kobsd against buffer concentration showed increases in kobsd of
less than 3% at 0.2 M buffer above the value of ko. Eyring plots
of ln(h(kobsd/kBT)) against 1/T are linear for 6 and 7 (six data
points each, r2 ) 0.999 and 0.998, respectively). The values of
the slopes permit calculation of ∆H† ) 21.8 ( 3.4 and 17.8 (
0.8 kcal/mol and the values of the intercepts permit calculation
of ∆S† ) -4.8 ( 1.1 and -8.2 ( 1.2 cal/deg mol.
The effect of acetate concentration on the values of kobsd/ko
is indicated in Figure 3. The experiments were carried out in
0.05 M cacodylic acid buffers containing 50% buffer base form.
(18) Paul, R.; Fluchaire, M.; Collardeau, G. Bull. Soc. Chim. Fr. 1950,
55, 668.