Nitrosation of Amines in Nonaqueous Solvents
J . Org. Chem., Vol. 64, No. 24, 1999 8891
Sch em e 3
Sch em e 4
DCEN
diate formation, k2 (Scheme 1), (k2)TCEN
morpholine/(k2)
morpholine
BrCH2CH2ONO
piperidine
) 6.46, (k2)DCEN
piperidine/(k2)
) 12.3, (b) that the
Ta ble 2. Qu a lita tive Dep en d en ce of Con sta n ts in
Sch em e 2 on th e Na tu r e of th e Am in e a n d Alk yl Nitr ite
relative values of k2 for the amines pyrrolidine, piperi-
dine, N,N′-dimethylethylenediamine, N-methylpipera-
zine, diethylamine, and morpholine exhibit practically
the same order as the reactivities of these amines with
the NdO group in water, generally increasing with the
basicity of the amine, and (c) that k2 is nevertheless much
less sensitive to amine basicity than is the reactivity
in water, ka2mine/km2 orpholine ) 13:3.3:3.3:2.2:1.4:1, respec-
tively, whereas in water ka2mine/km2 orpholine ) 167:32:28:
1.6:11.7:1, respectively.3 Findings (a) and (b) suggest that
in the transition state of T0 formation, N-N bond
formation must have progressed considerably more than
proton transfer, although finding (c) implies that some
degree of proton transfer has also occurred. Electron-
withdrawing substituted alkyl nitrites increase the elec-
trophilicity of the nitroso group and decrease the proton
affinity of the nitroso oxygen, hindering the intramolecu-
lar proton transfer. In the same way increasing the
basicity of the amine increases its nucleophilicity but
decreases its proton donor ability. We have also reported
that both the formation and decomposition of the inter-
mediate exhibit isotope effects indicative of proton trans-
fer in the slow steps.1 These conclusions are summarized
schematically in the More O’Ferrall diagram13 shown in
Scheme 3. Note that the HBC is shown in the bottom
left-hand corner of this diagram as being formed via the
nitroso oxygen of the alkyl nitrite, which is more nega-
tively charged than the alkoxide oxygen due to the
coexistence of the resonance structures 5 and 6. Although
k′′
k′′
K′′
k′′
2
-2
2
3
increasing the electron-withdrawing
groups on the RONO
increasing the amine basicity
v
v
V
v
v
v
v
vV
Introduction), suggest that k′′ must increase with the
3
ability of the amine to support positive charge, and hence
that the transition state of this step must lie below the
diagonal of the More O’Ferrall diagram of Scheme 4. This
location not only avoids the development of positive
charge on the alkoxide oxygen that occurs above the
diagonal, but is also supported by k′′ apparently being
3
increased in solvents with high proton donicity capable
of stabilizing the development of negative charge on the
alkoxide oxygen; in Cl3CH, for example, the rate-control-
ling step is the formation of the intermediate at all amine
concentrations in the range (2-1000) × 10-3 M.2
In view of the amine basicity argument justifying
Scheme 4, the results listed in Table 1 for k′′ have impli-
3
+
cations for the relative values of the pKRa NH of MMA
2
2
and MeAn in cyclohexane, which are not known. The fact
that k′′ is greater for MeAn/DCEN than for MMA/TCEN
3
means that pKRa NH +(MeAn) minus pKRa NH +(MMA)
must be large enough to outweigh TCEN’s being better
able to support negative charge on its alkoxide oxygen
2
2
2
2
than DCEN. This suggests that the difference in
+
pKRa NH between MeAn and MMA is greater in cyclo-
hexane than in water, in which they are quite similar
(4.85 and 4.75, respectively).
2
2
Table 2 summarizes the qualitative influence of the
natures of amine and alkyl nitrite on the constants
involved in the formation and decomposition of T0. We
have already seen that k′′ and k′′ are increased both by
2
3
increasing the basicity of the amine and by increasing
the number or efficacy of the charge-withdrawing groups
in the alkyl nitrite. Since increasing charge withdrawal
in the alkyl nitrite reduces its stability, it must diminish
the stabilization of alkyl nitrites by resonance is limited
by the scant capacity of oxygen to support positive charge,
and is thus less intense than the stabilization of N-
nitrosamines by resonance between 1 and 2, it is suf-
ficient to make the nitroso oxygen the preferred site for
hydrogen bonding (which parallels the behavior of car-
boxylic esters14).
k′′ and hence, given its effect on k′′, increase K′′.
-2
2
2
However, the positive charge on the amine nitrogen in
the transition state of the k′′ process implies that this
-2
constant may be expected to increase with the basicity
As regards the decomposition of T0, the nonaccumu-
lation of intermediate in our earlier studies with more
basic amines,1,2 and the partial positive charge on the
amine nitrogen of nitrosamines (as discussed in the
of the amine (leaving the response of K′′ to amine
2
basicity uncertain). Finally, KC may be expected to be
diminished both by increasing amine basicity and by
increasing charge withdrawal in the alkyl nitrite (which
reduces the negative charge on the hydrogen-bonding
nitroso group).
(13) (a) More O’Ferrall, R. A. J . Chem. Soc. B 1970, 274. (b) J encks,
W. P. Chem. Rev. 1972, 72, 705.
(14) (a) Nagy, J . B.; Nagy, O. B.; Bruylants, A. Bull. Soc. Chim. Belg.
1973, 82, 539. (b) Mukana, D.; Nagy, J . B.; Nagy, O. B.; Bruylants, A.
Bull. Soc. Chim. Belg. 1974, 83, 201. (c) Nagy, O. B.; Muanda, M.;
Nagy, J . B. J . Phys. Chem. 1979, 83, 1961.
Nitr osa tion of MeAn by TCEN. For T0 to ac-
cumulate, it must be generated faster than it is removed
by either the backward (k′′ ) or forward (k′′) decomposi-
-2
3