Mechanism of the Gibbs Reaction
J . Org. Chem., Vol. 64, No. 18, 1999 6539
transferred in a 25 mL normal flask, and borate buffer (5.0
mL), water (15 mL), and a solution of quinone 11b [0.30 mL
of asolution of 11b (26.9 mg, 0.15 mmol) dissolved in aceto-
nitrile (5 mL) and filled to 25 mL with water)] were added.
The volume was brought to 25 mL with water. The reaction
was monitored by UV where quinone 11b was also in the
reference solution. The conversion of N-chloroimine 1b to imine
6b was 70% after 30 min (6b λmax: 258 nm20).
P r ep a r a tion of Sp in Tr a p p in g Ad d u ct 12. N-chloroimine
1a (84 mg, 0.4 mmol) was dissolved in acetonitrile (10 mL)
and diluted with water (120 mL), and borate buffer (30 mL)
was added. A solution of TEMPO (25 mg, 0.16 mmol) in
acetonitrile (2 mL) and a solution of KCN (78 mg, 1.2 mmol)
in borate buffer (5 mL) were added. After 25 min at 25 °C, the
mixture was extracted with hexane (2 × 100 mL), the
combined organic extracts were washed with NaOH (0.1 M, 2
× 100 mL) (separation of the layers was facilitated by addition
of solid NaCl) and water (3 × 50 mL), dried, and evaporated.
Crude 12 was purified by preparative TLC (silica, benzene).
12 was contaminated with 13a and 14a according to 1H NMR.
12: 1H NMR (CDCl3) δ 8.56 (d, J ) 2.5 Hz, 1H), 7.42 (d, J )
2.5 Hz), 1.9-1.3 (m, 6H), 1.46 (s, 6H), 1.39 (s, 6H); 13C NMR
δ 172.4 (s), 138.9 (d), 131.7 (s), 129.2 (s), 127.4 (d), 127.3 (s),
88.6 (s), 74.6 (s), 42.3 (t), 39.5 (t), 27.7 (q, br), 19.5 (t). MS (EI)
m/z (rel intensity) 330/332 ([M]+•, 65/47), 315/317 ([M - •CH3]+,
52/37), 69 (100).
(q). MS (EI) m/z (rel intensity) 330/332 ([M]+• , 0.4/0.2), 313/
•
315 ([M - OH]+, 11/8), 69 (100).
Rea ction of N-Ch lor oim in e 1a w ith KCN. Solution A
(0.2 mL) was transferred into an NMR tube, and borate buffer
(0.2 mL), CD3CN (0.1 mL), and a solution of KCN [0.2 mL of
a solution of KCN (16 mg, 0.25 mmol) was dissolved in borate
buffer (0.2 mL) and D2O (2.3 mL)] were added. 1a : 1H NMR
δ 8.20 (s, br, 1H), 7.71 (s, br, 1H). 6a : 7.62 (s, br, 1H), 7.42 (s,
br, 1H) (the spectra should be recorded within 8 min). After
recording the spectra, the solution was extracted with CDCl3
(0.5 mL), and the 1H NMR spectra was recorded again. 1a :
1H NMR δ 8.02 (d, J ) 2.6 Hz, 1H), 7.55 (d, J ) 2.6 Hz, 1H).
6a : 7.51 (d, J ) 2.3 Hz, 1H), 7.21 (d, J ) 2.3 Hz, 1H) (the
ratio of 1a /6a was ≈ 55/45). Then, 0.1 mL of the dried CDCl3
layer was diluted with n-hexane (4 mL) to record the UV
spectrum of the mixture: 1a (λmax 301 and 310 nm) and 6a
(λmax 278 nm, shoulder at 270 nm). When a mixture of
2-propanol (0.1 mL), water (2 mL), and borate buffer (0.1 mL)
was added to the CDCl3 solution (0.1 mL), the unreacted
N-chloroimine 1a was transformed into imine 6a immed-
iately.37b,c
Rea ction of N-Ch lor oim in e 1a w ith KCN in th e P r es-
en ce of TEMP O. Compound 1a (21 mg, 0.1 mmol) was
dissolved in CD3CN (2 mL). Then, 0.2 mL of this solution was
transferred into an NMR tube, and CD3CN (0.1 mL), borate
buffer (0.2 mL), TEMPO [0.1 mL of a solution of TEMPO (15.6
mg, 0.1 mmol) dissolved in CD3CN (0.1 mL) and D2O (1.9 mL)],
and KCN [0.4 mL of solution of KCN (6.5 mg, 0.1 mmol)
dissolved in borate buffer (0.2 mL) and D2O (1.8 mL)] were
P r ep a r a tion of Sp in Tr a p p in g Ad d u cts 13a a n d 14a .
N-chloroimine 1a (147 mg, 0.7 mmol) was dissolved in aceto-
nitrile (5 mL) and diluted with water (10 mL), and TEMPO
[109 mg, 0.7 mmol in acetonitrile (5 mL) and in water (5 mL)]
and KCN (182 mg, 2.8 mmol in borate buffer (20 mL) were
added. After 10 min at 25 °C, the pH was adjusted to 5-6
with HCl. The reaction mixture was extracted with chloroform
(2 × 25 mL), and the combined organic extracts were washed
with borate buffer (2 × 20 mL) and water (2 × 30 mL), dried,
and concentrated. The crude product (the ratio of 13a /14a was
∼1/1) was purified on preparative TLC (silica, benzene). 13a
and 14a were isolated as a mixture and characterized with
UV, 1H and 13C NMR, and mass spectrometry. The pH
dependence of the UV spectrum in a basic medium suggests
that both compounds have a phenolic hydroxyl group. The
dissociation is considerable in both water and 95% ethanol,
showing that the aromatic nucleus carries substituents with
negative inductive effect. Both the neutral and the dissociated
form show a pronounced bathochromic effect compared to the
spectrum of 2,6-dichlorophenol 4g. This indicates that the para
substituent is in donor-acceptor interaction with the phenolic
hydroxyl which facilitates delocalization. λmax (95% ethanol)
315 and 367 nm; λmax 306 nm (with one drop of 0.1 N HCl
added to the solution (4 mL) in the cuvette); and λmax 363 nm
(with one drop of triethylamine added). (The corresponding
data for phenol 4g are 282 and 302 nm in neutral, 282 nm in
acidic, and 302 nm in basic media, respectively.) According to
1
added. Monitoring the reaction with H NMR, the consumption
of 1a (s,br) was observed, but in the presence of TEMPO 1a
gave compounds 12, 13a , and 14a instead of 6a . When the
experiment was repeated without KCN, although 1a was
decomposed in a radical reaction again in the alkaline solution,
compounds 12, 13a , and 14a were formed, but in a signifi-
cantly lower ex´ıtent.
Rea ction of N-Ch lor oim in e 1b w ith P h en ol 4a in th e
P r esen ce of TEMP O. To a solution of 1b (26 mg, 0.2 mmol)
in acetonitrile (1 mL) were added a solution of phenol 4a (67
mg, 0.7 mmol) in acetonitrile (0.5 mL), borate buffer (5 mL,
50 mM, D2O), and a solution of TEMPO (31 mg, 0.2 mmol) in
acetonitrile (0.5 mL) and D2O (3 mL) (with D2O the rate was
higher than with H2O). After 5 h at 25 °C, water (10 mL) was
added, and the pH was adjusted to 5.5-6.5 with HCl. The
mixture was extracted with CHCl3 (2 × 10 mL), and the
combined organic layers were washed with water (l0 mL),
dried, and concentrated to 0.5-1 mL at reduced pressure
(water bath temperature 30-35 °C). Then n-hexane (25 mL)
was added, and the organics were washed with HCl (0.1 M, 2
× 20 mL) and water (2 × 10 mL) to separate from indophenol
3 and the excess of phenol, dried and evaporated. 1b: 1H NMR
(acetone-d6, T ) 323 K, reference standard TMS) δ 7.72 (dd,
J 1 ) 10.2 Hz, J 2 ) 2.7 Hz, 1H), 1H), 7.21 (dd, J 1 ) 10.2 Hz, J 2
) 2.7 Hz), 6.54 (dd, J 1 ) 10.2 Hz, J 2 ) 1.3 Hz, 1H), 6.44 (dd,
J 1 ) 10.2 Hz, J 2 ) 1.3 Hz, 1H). 13b: 8.35 (s, br, OH), 7.82 (d,
J ) 8.0 Hz, 2H), 6.74 (d, J ) 8.0 Hz, 2H), 4.78 (s, br, 2H).
14b: 8.35 (s, br, OH), 7.82 (d, J ) 8.0 Hz, 2H), 6.74 (d, J )
8.0 Hz, 2H), 5.0 (br, 1H). MS (EI) m/z (rel intensity) 262 ([M]+•,
1
the H and 13C NMR spectra, in 13a and 14a , the part derived
from N-chloroimine 1a was reduced into a phenol derivative
and the piperidine ring of TEMPO was cleaved in both cases;
however, whereas in the structures of 13a one of the methyl
groups was turned into a terminal double bond, in 14a a CHd
•
2), 245 ([M - OH]+, 28), 121 (10), 69 (100).
1
1
C(CH3)2 group was formed. H homo decoupling and H NOE
difference experiments made the identification of the charac-
teristic signals of 13a and 14a possible. 13a : 1H NMR (C6D6,
T ) 318 K) δ 8.17 (s, 2H, overlapping with the signal 14a ),45
5.47 (br, 1H, exchangeable with D2O; overlapping with the
signal 14a ), 4.75 (s, br, 1H), 4.71 (s, br, 1H), 1.57 (s,br, 3H),
1.39 or 1.38 (s, 6H). 14a : 8.17 (s, 2H), 5.47 (br, 1H, exchange-
able with D2O; overlapping with the signal 13a ), 5.07 (t, br, J
) 6.9 Hz and ∼1 Hz with two methyls), 1.60 (s, br, 3H), 1.47
(s, br, 3H), 1.39 or 1.38 (s, 6H). 13a and 14a :13C NMR (CDCl3,
298 K) δ 147.7 (s), 145.0 (s), 137.6 (s), 132.4 (s), 125.4 (d), 123.0
(d), 120.4 (s), 110.4 (t), 80.7 (s), 80.6 (s), 41.1 (t), 40.8 (t), 37.6
(t), 26.4 (q), 26.4 (q), 25.6 (q), 22.9 (t), 22.2 (q), 21.9 (t), 17.6
Rea ction of N-Ch lor oim in e 1a w ith 2,4,6-Tr i-ter t-bu -
tylp h en ol 4h . Meth od a (r ea ction w ith ou t d eoxigen a -
tion , in 17 vol % a qu eou s a ceton itr ile). To a solution of
N-chloroimine 1a (105 mg, 0.5 mmol) in acetonitrile (20 mL)
and water (200 mL) were added borate buffer (20 mL), TEMPO
(6 mg, 0.04 mmol) in acetonitrile (1 mL), and 4h (39 mg, 0.15
mmol) in acetonitrile (25 mL). After shaking and standing for
25 min at room temperature, the mixture was neutralized with
HCl and extracted with chloroform (2 × 100 mL). The organic
phase was washed with water (100 mL), dried (Na2SO4), and
concentrated to 5 mL (water pump, max. 30 °C). Then, 2-3
drops of 1,1,2,2-tetrachloroethane-d2 (TCE-d2) were added, and
after the removal of the rest of the chloroform, CDCl3 (0.5 mL)
was added. 1a : 1H NMR δ (reference, the signal of TCE-d2,
6.00 ppm) 7.97 (d, J ) 2.6 Hz, 1H), 7.49 (d, J ) 2.6 Hz, 1H).
13a and 14a : 8.02 (s, br, 2 × 2H), 5.04 (br, 1H, overlapping
(45) The chemical shifts (δ) of the aromatic protons of 13a and 14a ,
respectively, were 8.07 and 8.08 in CDCl3 (or tetrachloroethane-d2).