Toward a 6π+6π zwitterion or a bioinhibitors-related OH-substituted aminoquinone: Identification of a key intermediate in their pH controlled synthesis

Article abstract of DOI:10.1002/chem.200400244

Their pH-controlled reactivity places the N,N-dialkyl-2-amino-5-lithium alcoholate-,4-benzoquinonemonoimines [C₆H₂(NHCH ₂R′) (=NCH₂R′)(=O)(OLi)] 7 (R′ = tBu) and 8 (R′ =p-C₆H₄-tBu) at the c

Full text of DOI:10.1002/chem.200400244

FULL PAPER
Toward a 6p+6p Zwitterion or a Bioinhibitors-Related OH-Substituted
Aminoquinone: Identification of a KeyIntermediate in Their pH Controlled
Synthesis
Pierre Braunstein,* Olivier Siri, Jean-philippe Taquet, and Qing-Zheng Yang[a]
Dedicated to Professor Pierre Potier on the occasion of his 70th birthday
Abstract: Their pH-controlled reactivi-
ty places the N,N’-dialkyl-2-amino-5-
lithium alcoholate-1,4-benzoquinone-
tive substituted aminobenzoquinones,
for which changes of the N-substituent
will become readily possible. The
results of the first X-ray structural
determination of such compounds
the influence of the number of N-sub-
stituents of the C6 ring on the
supramolecular networks resulting
from self-assembling of 13, zwitter-
ionic N,N’-dineopentyl-2-amino-5-alco-
holate-1,4-benzoquinonemonoiminium
monoimines
(=NCH2R’)(=O)(OLi)]
[C6H2(NHCH2R’)
(R’=tBu)
7
and 8 (R’=p-C6H4-tBu) at the cross-
roads of a new versatile strategy for
the preparation of two very different
classes of substituted quinones. We de-
scribe new 2-(N-alkyl)amino-5-hy-
droxy-1,4-benzoquinones, which are
parent molecules to biologically ac-
([C6H2(NHCH2tBu)(OH)(=O)2]
13)
are also reported and we compare
[C6H2(PNHCH2tBu)2(PO)2]
9
and
N,N’,N’’,N’’’-tetraneopentyl-2,5-diamino-
1,4-benzoquinone diimine [C6H2(NHCH2-
tBu)2(=NCH2tBu)2] 15.
Keywords: p interactions ¥ amino-
quinones ¥ supramolecular chemis-
try ¥ synthetic methods ¥ zwitterions
Introduction
The synthesis of quinonoid
molecules has attracted the at-
tention of a large scientific
community for decades owing
to their importance in many
areas of chemistry and biolo-
gy.[1] In particular, benzoqui-
nones containing an hydroxy
group of type 1 are of considerable interest in biochemistry
since closely related C-substituted benzoquinones such as
the marine quinone sesquiterpenes nakijiquinone A (2) and
smenospongidine (3) or embelin derivatives 4 possess very
weight analogues of these inhibitors is considered to repre-
sent a most promising approach towards the development of
new alternative antitumor drugs.[2]
Despite very intensive research efforts directed towards
the synthesis of OH-substituted benzoquinones, their access
10]
diverse and remarkable biological activities.[2
11]
Quinones with an OH substituent play an important role
as inhibitors of hydroxyphenylpyruvate dioxygenase,[4] of
tumors[2] or of the receptor tyrosine kinase involved in an-
giogenesis by interaction with the ATP binding site through
hydrogen bonding.[2] The development of low molecular
has remained rather limited.[5,9 A simple and more versa-
tile route that would not require their extraction from natu-
ral products,[4,5,10] multisteps procedures,[2,3] or oxidation
processes before nucleophilic attack of amines[11] or water[12]
on the quinonoid skeleton would obviously be of considera-
ble interest.
[a] Dr. P. Braunstein, Dr. O. Siri, J.-p. Taquet, Dr. Q.-Z. Yang
Laboratoire de Chimie de Coordination
UMR 7513 CNRS Universitÿ Louis Pasteur
4, rue Blaise Pascal, 67070 Strasbourg Cÿdex (France)
Fax : (+33)390-241-322
To the best of our knowledge, only four molecules of type
1 (i.e., without substitution at the olefinic carbon) have
been described in the literature: one compound for which R
is a phenyl group[11] and three compounds for which R is a
carbonyl substituent.[12,13] Although theoretical calculations
E-mail: braunst@chimie.u-strasbg.fr
Chem. Eur. J. 2004, 10, 3817 3821
DOI: 10.1002/chem.200400244
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FULL PAPER
have been performed on molecules such as 1 for which R is
a phenyl group and on hypothetical analogues with aryl sub-
stituents, no X-ray structural analysis is available.[5]
zwitterions 9 and 10 in high yield (assignment of the 1H
NMR resonance for the NCH2 protons is facilitated by the
3
occurrence of a JHH coupling in [D6]DMSO, see Experimen-
Herein, we report the high yield synthesis of new OH-
substituted aminoquinones [C6H2(NHCH2R’)(OH)(=O)2] re-
lated to 1, for which the N-susbtituent is an alkyl group.
These compounds, 13 (R’=tBu) and 14 (R’=p-C6H4-tBu),
which may be considered as parent compounds to 2 and 3,
were obtained from versatile alcoholate precursors
[C6H2(NHCH2R’)(=NCH2R’)(=O)(OLi)] 7 (R’=tBu) and 8
(R’=p-C6H4-tBu), that are also able to lead under different
pH conditions to zwitterionic p-benzoquinonemonoimines,
tal Section). We have now found that prior dissolution of 7
and 8 in a mixture of THF/H2O containing LiOH (basic
pH) prevents protonation and instead leads by slow hydroly-
sis to the alcoholates intermediates 11 and 12, which can be
subsequently protonated to the OH-substituted amino-p-
benzoquinones [C6H2(NHCH2tBu)(OH)(=O)2] 13 and
[C6H2(NHCH2-p-C6H4-tBu)(OH)(=O)2] 14, respectively, in
good yields (Scheme 1).
The highest yields of 13 and 14 were obtained by direct
synthesis without isolation of the intermediates 7 and 8
since their competitive protonation which leads to the zwit-
terions 9 and 10 cannot be completely avoided (see Experi-
mental Section). However, we have found that selective
mono-deprotonation of 9 or 10 with LiOH in THF affords
in high yields 7 and 8, respectively.
known
[C6H2(PNHCH2tBu)2(PO)2]
9[15]
and
new
[C6H2(PNHCH2p-C6H4-tBu)2(PO)2] 10, respectively. Nonco-
valent interactions such as hydrogen bonding are suggested
to participate in the interactions between nakijiquinones
and the ATP binding sites of kinases,[2] and we will examine
if our systems have interesting potential as tunable building
blocks in hydrogen-bonded molecular networks.
1
The H NMR spectrum of 13 contains two signals at 6.62
and 8.24 ppm for the N-H and O-H protons, respectively,
whereas its 13CNMR spectrum confirmed the presence of
two carbonyl groups (d(C=O)=178.27 and 182.52 ppm).
Contrary to the UV/Vis spectra of the zwitterions which re-
vealed two strong absorptions at 350 nm (log e=4.49) and
343 nm (log e=4.45) for 9,[15] 352 nm (log e=4.25) and
340 nm (log e=4.23) for 10, that of 13 is characterized by
only one strong absorption at 303 nm (log e=4.11) which
corresponds to the intraquinone charge transfer, and by the
presence of one more band at 486 nm (log e=3.26). Similar-
ly, 14 revealed in CH2Cl2 two absorption bands at 301 nm
(log e=3.97) and 478 nm (log e=3.16). The main absorp-
tions can be attributed to the p p* transition of the benzo-
Results and Discussion
A straightforward synthesis of the p-benzoquinonemono-
imine (9), which is a rare example of zwitterion being more
stable than its canonical forms, was recently described from
5.[14] To explain the formation of this unique 12 p electron
system, which is actually best described as constituted of
two chemically connected but electronically not conjugated
6 p electron subunits (Scheme 1),[14] we suggested that inter-
mediate B (not isolated in CH2Cl2) would rearrange to 9 by
proton migration from oxygen onto the more basic nitrogen
atom.[15] By studying this reac-
tion in more detail, we have
now isolated and characterized
a new intermediate 7, obtained
during the air oxidation
workup of intermediate A. Its
13CNMR spectrum contains
two signals at d=162.53 and
180.07 ppm which are consis-
tent with a localized p-system
À
(d(C O) and d(C=O), respec-
tively), in contrast to 9 for
which the negative charge is
delocalized between the two
oxygen
atoms
(d(CPO)=
172.13 ppm).[15] The diester di-
amido derivative 6, obtained
by reaction between 4,6-diami-
noresorcinol dihydrochloride
and (4-tert-butyl)-benzoyl chlo-
ride, was reduced with LiAlH4
and the subsequent aerobic
workup similarly led to
8
(Scheme 1). In the presence of
water, 7 and 8 afforded by
rapid protonation intermediate
B
which rearranges to the
Scheme 1.
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OH-Substituted Aminoquinones
3817 3821
quinone derivatives, whereas the weak absorption band cor-
responds to a n p* transition originating at the nitrogen
lone pair.[16] Recent publications[17,18] have described theo-
retical analyses of 9. Sawicka, Skurski and Simons[17] as-
signed the band at 350 nm to the first p p* absorption and
that at 343 nm to a vibrational excitation on top of the elec-
tronic transition, whereas if Delaere, Nam and Nguyen[18a]
confirmed that both UV absorption peaks at 350 and
343 nm belong to the same electronic transition but with dif-
ferent vibrational states, they assigned them to a transition
from the ground electronic state to the second 21B2 state
rather than to the first 11B2 state.
An X-ray diffraction study on single crystals of 13,[19] ob-
tained by slow evaporation of a dichloromethane solution,
established the p-benzoquinone structure of the molecule
À
À
and showed that the C(1) C(2) and C(4) C(5) distances of
1.504(2) and 1.521(2) ä, respectively, correspond to two
single bonds (Figure 1).
Figure 2. a) View of the stacking arrangement generated by 13 in the
solid state. b) View of the supramolecular array generated by 13 in the
solid state. Colour coding: nitrogen, blue; oxygen, red; hydrogen, green.
(Figure 2). It is interesting to recall that similar H-bond
donors in nakijiquinones are suggested to participate in hy-
drogen bonding to the ATP binding sites of kinases.[2]
For comparison, it is relevant to recall that two related
molecules, which also possess two H-donor sites and two H-
acceptor sites, form different supramolecular architectures
in the solid state. Although 9 led also to the formation of a
head-to-tail hydrogen-bonded network, it revealed an unex-
pected wave-like arrangement owing to the presence of two
N-neopentyl substituents (Figure 3a).[15]
Figure 1. View of the structure of 13 in the crystal. Selected bond lengths
À
À
À
[ä] and angles [8]: O(1) C(5) 1.330(2), C(5) C(8) 1.344(2), C(8) C(6)
À
À
À
1.440(2), C(6) O(2) 1.231(2), C(5) C(2) 1.504(2), C(6) C(4) 1.521(2),
À
À
À
À
O(3) C(2) 1.242(2), C(2) C(3) 1.418(2), C(3) C(4) 1.374(2), C(4) N(1)
1.332(2); O(1)-C(5)-C(8) 121.8(1), C(5)-C(8)-C(6) 120.2(1), C(8)-C(6)-
O(2) 122.7(1), O(1)-C(5)-C(2) 116.4(1), O(2)-C(6)-C(4) 118.7(1), C(5)-
C(2)-O(3) 117.0(1), C(6)-C(4)-N(1) 113.6(1), O(3)-C(2)-C(3) 124.4(1),
C(2)-C(3)-C(4) 121.0(1), C(3)-C(4)-N(1) 126.7(1).
With four N-neopentyl substituents, the 2,5-diamino-1,4-
Examination of the bond lengths within the O(1)-C(1)-
C(6)-C(5)-O(3) and O(2)-
benzoquinonediimine
[C6H2(NHCH2tBu)2(=NCH2tBu)2]
C(2)-C(3)-C(4)-N
moieties
reveal an alternating succes-
sion of single and double
bonds which is consistent with
two independent conjugated
but not delocalized p systems.
Furthermore, the O(1)-H(1)
and N-H(4) protons of 13 es-
tablish intramolecular hydro-
gen bonding with the H-bond
acceptor
quinone
oxygen
atoms O(2) and O(3), respec-
tively. Compound 13 forms in-
termolecular interactions in
the solid state which lead to a
p-stacking arrangement of
head-to-tail H-bonded copla-
Figure 3. a) View of the head-to-tail array generated by 9 in the solid state. b) View of the stacking arrange-
ment generated by 15 in the solid state. Colour coding: nitrogen, blue; oxygen, yellow; hydrogen, red.
nar
six-membered
rings
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P. Braunstein et al.
FULL PAPER
15[20] led instead to a different packing
arrangement owing to the steric hin-
drance induced by the presence of
these four substituents (Figure 3b).[21]
In this case, the stacking results from
intermolecular p p interactions.
N,N’-Dineopentyl-2-amino-5-lithiumalcoholate-1,4-benzoquinonemono-
imine (7) and N,N’-di-(4-tert-butylbenzyl)-2-amino-5-lithium alcoholate-
1,4-benzoquinonemonoimine (8)
General procedure A: Diamido diester 5 or 6 was dissolved in dry THF
and an excess of LiAlH4 (10 equiv) was added to the solution. The mix-
ture was then refluxed for 4 h and excess of LiAlH4 was quenched by ad-
dition of water (2 mL). After filtration of aluminium salts and evapora-
tion of the solution to dryness, the orange product was suspended in di-
chloromethane to remove soluble zwitterion and residual impurities, and
the solid was collected by filtration.
The present study has demonstrated
the chemical versatility of the inter-
mediates 7 and 8 and confirmed that although molecules 9,
13 and 15 possess two H-donor sites and two H-acceptor
sites, the number of N-substituents as well as the nature of
the atoms involved in the hydrogen-bonding interactions
(i.e., oxygen or nitrogen) play a key role in the construction
of supramolecular architectures.
General procedure B: Zwitterion 9 or 10 was dissolved in anhydrous
THF (50 mL) and 1 equiv solid LiOH was added to the solution. The
mixture was then stirred overnight at room temperature. After evapora-
tion of the solvent, 7 and 8, respectively, were obtained quantitatively as
orange powders and used without further purification.
Compound 7: MS (FAB+, 70 eV): m/z: 285.2 [M+H]+; 1H NMR
3
(300 MHz, [D6]DMSO): d = 0.93 (brs, 18H, CH3), 2.86 (d, JHH =5.7 Hz,
2H, HNCH2), 3.05 (s, 2H, CH2), 4.98 (s, 1H, N-C=C-H), 5.20 (s, 1H, O-
C=C-H), 6.28 (brt, 1H, N-H); 13C{1H} NMR (125.8 MHz, [D6]DMSO): d
Conclusion
=
27.34 (CMe3), 28.10 (CMe3), 32.05 (CMe3), 32.16 (CMe3), 52.73
(CH2N), 62.17 (CH2N), 83.47 (H-C=C), 99.78 (H-C=C), 147.16 (C-N),
162.53 (C-O), 176.68 (C=N), 180.07 (C=O); 7Li NMR (155.5 MHz,
[D6]DMSO) d = 0.35 (brs).
Compound 8: MS (FAB+, 70 eV): m/z: 437.5 [M+H]+; 1H NMR
Because of their versatile pH-controlled reactivity, com-
pounds 7 and 8 are at the crossroads of a new strategy for
the preparation of two very different classes of substituted
aminobenzoquinones: 6p+6p zwitterions such as 9 and 10
or OH-substituted aminobenzoquinones of type 1, such as
13 and 14, for which changes of the N-substituent become
readily possible. The first structural determination of a com-
pound of the latter type is now available with molecule 13
which can be used for future correlations with theoretical
calculations performed on analogues.[5] In addition to their
relevance to bioinhibitor molecules, these OH-substituted
aminobenzoquinones have furthermore a considerable po-
tential in inorganic chemistry since they present two differ-
ent bidentate donor sets suitable for the preparation of het-
erobinuclear complexes.
(300 MHz, [D6]DMSO): d = 1.27 (brs, 18H, CH3), 4.35 (brs, 4H, CH2),
À
À
4.90 (brs, 1H, N-C=C-H), 5.30 (brs, 1H, O C=C H), 7.20 (brd, A part
of an AB system, 3JHH =7.5 Hz, 4H, C-H aryl), 7.30 (brd, B part of an
AB system, 3JHH =7.5 Hz, 4H, C H aryl. Owing to the poor solubility of
À
8, it was impossible to obtain a 13CNMR spectrum.
N,N’-Dineopentyl-2-amino-5-alcoholate-1,4-benzoquinonemonoiminium
(9) and N,N’-di-(4-tert-butylbenzyl)-2-amino-5-alcoholate-1,4-benzoqui-
nonemonoiminium (10)
General procedure A (one-pot procedure from 5 and 6 without isolation
of 7 and 8): Similarly to the procedure previously described for the syn-
thesis of 9,[15] compound 10 was obtained as a purple solid.
General procedure B (procedure from 7 and 8): Compound 7 or 8 was
dissolved in a water/dichloromethane mixture. The zwitterions 9[15] and
10 were extracted in the dichloromethane phase and after drying on mag-
nesium sulfate, evaporation of the solvent and recrystallisation from a di-
chloromethane/hexane, isolated in quantitative yields as purple solids. In
order to see all 13CNMR signals, it was essential to increase the pulse
delay from 0.8 to 2 s.
Experimental Section
Compound 10: (1.05 g, 80% based on 6). HRMS (EI+, 70 eV): m/z:
calcd for: 431.2698; found: 431.2657 [M+H]+; 1H NMR (300 MHz,
CDCl3): d = 1.33 (s, 18H, CH3), 4.50 (s, 4H, CH2), 5.34 (s, 1H, NPCPC-
General: Analytical-grade reagents were obtained from commercial sup-
pliers and were used directly without further purification. Solvents were
distilled under argon prior to use and dried by standard methods. All re-
duction reactions were performed under N2. 1H NMR spectra were re-
corded in CDCl3 and [D6]DMSO with a AC300 Bruker spectrometer, op-
erating at 300 MHz for 1H spectra. Chemical shifts are reported in parts
per million (ppm) relative to the singlet at d=7.26 for CDCl3. Splitting
patterns are designated as s, singlet; d, doublet; t, triplet; br, broad. Ele-
mental analyses were performed by the ™service de microanalyse de
l×universitÿ Louis Pasteur,∫ Strasbourg. FAB mass spectral analyses were
recorded on an autospec HF mass spectrometer and EI high resolution
mass spectral analyses were recorded on a Finnigan TSQ 700.
3
À
H), 5.44 (s, 1H, OPCPC H), 7.20 (d, A part of an AB system, JHH
=
8.35 Hz, 4H, C-H aryl), 7.42 (d, B part of an AB system, 3JHH =8.35 Hz,
1
4H, C-H aryl), 8.52 (brs, 2H, N-H); H NMR (300 MHz, [D6]DMSO): d
=
1.27 (s, 18H, CH3), 4.58 (d, 3JHH =6.3 Hz, 4H, CH2), 4.97 (s, 1H,
NPCPC-H), 5.76 (s, 1H, OPCPC-H), 7.28 (d, A part of an AB system,
3
3JHH =8.35 Hz, 4H, C-H aryl), 7.35 (d, B part of an AB system, JHH
=
8.35 Hz, 4H, C-H aryl), 9.66 (t, 2H, N-H); 13C{1H} NMR (75 MHz,
CDCl3): d = 31.29 (CMe3), 34.70 (CMe3), 47.24 (CH2N), 81.61 (H-C=C),
98.91 (H-C=C), 126.23, 127.71 (H-C aryl), 131.00, 151.98 (C aryl), 156.95
(CPN), 172.13 (CPO); elemental analysis calcd (%) for C28H34N2O2¥H2O:
C74.97, H 8.09, N 6.24; found: C74.87, H 7.48, N 6.28.
Synthesis of the diester diamidobenzene 6: Similarly to the procedure de-
scribed for the synthesis of analogues,[15] compound 6 was obtained as a
white solid (2.38 g, 65%). HRMS (EI+, 70 eV): m/z: calcd for: 781.4216;
found: 781.4042 [M+H]+; 1H NMR (300 MHz, CDCl3): d=1.30 (s, 18H,
CH3), 1.36 (s, 18H, CH3), 7.34 (s, 1H, aromatic), 7.39 (d, A part of an
2-(Neopentyl)amino-5-hydroxy-1,4-benzoquinone (13) and 2-(4-tert-bu-
tylbenzyl)amino-5-hydroxy-1,4-benzoquinone (14)
General procedures
Procedure A (one-pot procedure from 5 and 6 without isolation of 7 and
8): Diamido diester 5 (1.00 g, 2.10 mmol) or 6 (1.00 g, 1.28 mmol) was dis-
solved in dry THF and an excess of LiAlH4 (10 equiv) was added to the
solution. The mixture was then refluxed for 4 h, excess LiAlH4 was
quenched by addition of water (100 mL) and this suspension was stirred
overnight at room temperature. The aluminium salts were filtered and di-
chloromethane added to the THF/H2O. Protonation of the water-soluble
alcoholate 11 followed by dichloromethane extraction, drying on magne-
sium sulfate and evaporation of the solvent afforded 13 as a red-orange
solid. For 14, addition of dichloromethane to the THF/H2O solution ex-
AB system, 3JHH =8.7 Hz, 4H, C H aryl), 7.52 (d, A part of an AB
À
system, 3JHH =8.7 Hz, 4H, C H aryl), 7.72 (d, B part of an AB system,
À
3JHH =8.7 Hz, 4H, C H aryl), 8.12 (d, B part of an AB system, JHH
=
3
À
8.7 Hz, 4H, C H aryl), 8.16 (s, 2H, N-H), 9.05 (s, 1H, aromatic); 13C{1H}
NMR (75 MHz, CDCl3): d = 31.09 (CMe3), 31.12 (CMe3), 34.96 (CMe3),
35.30 (CMe3), 116.68, 118.93, 126.65, 125.84, 127.08, 130.33 (H-Caryl),
125.72, 128.19, 131.50, 138.56, 155.43, 158.14 (Caryl), 164.39 (C =O),
165.27 (C=O); elemental analysis calcd (%) for C50H56N2O6: C76.89, H
7.23, N 3.59; found: C76.78, H 7.29, N 3.56.
À
3820
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OH-Substituted Aminoquinones
3817 3821
tracts traces of zwitterion 10 and leads to the formation of a pink precipi-
tate collected by filtration. The THF/H2O phase is then discarded and
the precipitate suspended in a water/dichloromethane mixture. Addition
of HCl, dichloromethane extraction, drying of the solution on magnesium
sulfate and evaporation of the solvent leads to 14 as a red-orange solid.
[4] G. Meazza, B. E. Scheffler, M. R. Tellez, A. M. Rimando, J. G. Ro-
magni, S. O. Duke, D. Nanayakkara, I. A. Khan, E. A. Abourashed,
F. E. Dayan, Phytochemistry 2002, 59, 281.
[5] M. Aguilar-MartÏnez, J. A. Bautista-MartÏnez, N. MacÏas-Ruvalcaba,
I. Gonz‡lez, E. Tovar, T. M. del Alizal, O. Collera, G. Cuevas, J.
Org. Chem. 2001, 66, 8349.
[6] N. U. Frigaard, S. Tokita, K. Matsuura, Biochim. Biophys. Acta 1999,
1413, 108.
[7] J. J. Inbaraj, R. Gandhidasan, R. Murugesan, Free Radical Biol.
Med. 1999, 26, 1072.
[8] N. R. Bachur, S. L. Gordon, M. V. Gee, Cancer Res. 1978, 38, 1745.
[9] N. Subbarayudu, Y. D. Satyanarayana, E. Venkata-Rao, D. Venkata-
Rao, Ind. J. Pharm. Sc. 1978, 40, 173.
[10] B. S. Joshi, V. N. Kamat, Ind. J. Chem. 1975, 13, 795.
[11] M. K. Manthey, S. G. Pyne, R. J. W. Truscott, Aust. J. Chem. 1989,
42, 365.
[12] P. D. Mize, P. W. Jeffs, K. Boekelheide, J. Org. Chem. 1980, 45, 3540.
[13] H. Hitomi, M. Yutaka, K. Yutaka, H. Mitsunobu, A. Kazuhito, A.
Shiro, M. Chikara, I. Shun-ichi, S. Kendo, WO 9817629, 1998.
[14] P. Braunstein, O. Siri, J.-P. Taquet, M.-M. Rohmer, M. Bÿnard, R.
Welter, J. Am. Chem. Soc. 2003, 125, 12246.
[15] O. Siri, P. Braunstein, Chem. Commun. 2002, 208.
[16] R. Zhang, H. Zheng, J. Shen, J. Mol. Struct. 1998, 446, 103.
[17] A. Sawicka, P. Skurski, J. Simons, Chem. Phys. Lett. 2002, 362, 527.
[18] a) D. Delaere, P.-C. Nam, M. T. Nguyen, Chem. Phys. Lett. 2003,
382, 349; b) H. T. Le, P.-C. Nam, V. L. Dao, T. Veszprÿmi, M. T.
Nguyen, Mol. Phys. 2003, 101, 2347.
Procedure B (procedure from 7 and 8): Compound 7 or 8, best obtained
from 9 and 10, were dissolved in THF/H2O 1:1 (100 mL) and a concen-
trated solution of LiOH in water (pH > 10) was added to the solution
which was then stirred overnight at room temperature. Protonation of
the water-soluble alcoholates 11 and 12, respectively, followed by di-
chloromethane extraction, drying on magnesium sulfate and evaporation
of the solvent afforded quantitatively 13 and 14 as red-orange solids. Red
crystals of 13 suitable for X-ray analysis were isolated by slow evapora-
tion of a dichloromethane solution.
Compound 13: (80% based on 5). MS (FAB+, 70 eV): m/z: 210 [M+H]+;
1H NMR (300 MHz, CDCl3): d = 1.01 (s, 9H, CH3), 2.95 (d, 3JHH =6.4 Hz,
À
À
2H, CH ), 5.46 (s, 1H, N-C=C-H), 5.91 (s, 1H, O C=C H), 6.62 (brs, 1H,
2
N-H), 8.24 (brs, 1H, OH); 13C{1H} NMR (75 MHz, CDCl3): d = 27.44
(s, CMe3), 32.42 (s, CMe3), 54.26 (s, CH2N), 92.22 (s, H-C=C), 102.25 (s,
À
À
H-C=C), 150.44 (s, C N), 159.49 (s, C O), 178.27 (s, C=O), 182.52 (s,
C=O); elemental analysis calcd (%) for C11H15NO3: C63.14, H 7.23,
N 6.69; found: C62.77, H 7.52, N 6.67.
Compound 14: (46% based on 6). HRMS (EIÀ, 70 eV): m/z: calcd for:
284.1286; found: 284.1326 [MÀH]+; 1H NMR (300 MHz, CDCl3): d =
1.33 (s, 9H, CH3), 4.31 (d, 3JHH =5.7 Hz, 2H, CH2), 5.51 (s, 1H, N-C=C-
H), 5.92 (s, 1H, O-C=C-H), 6.63 (brs, 1H, N-H), 7.20 (d, A part of an
AB system, 3JHH =8.1 Hz, 2H, C-H aryl), 7.40 (d, B part of an AB
system, 3JHH =8.1 Hz, 2H, C-H aryl), 8.14 (brs, 1H, OH); 13C{1H} NMR
[19] Crystal data for 13: C11H15NO3, M=209.24, triclinic, space group
≈
P1; a=5.732(5), b=9.787(5), c=10.020(5) ä, a=105.188(5), b=
(100 MHz, CDCl3): d
= 31.33 (s, CMe3), 34.69 (s, CMe3), 46.83 (s,
100.990(5), g=90.945(5)8, V=531.2(6) ä3, Z=2, m(MoKa)=
CH2N), 93.09 (s, H-C=C), 102.51 (s, H-C=C), 126.13, 127.63 (s, H-C aryl),
0.71069 mmÀ1
,
T=173(2) K, 2309 data with I>2s(I), final R=
0.0696, Rw=0.1217, GOF=0.923. Selected crystal was mounted on
Nonius Kappa-CCD area detector diffractometer (MoKa l=
À
À
131.97, 149.70 (Caryl), 151.66 (s, C N), 159.11 (s, C O), 178.59 (s,
C=O), 182.57 (s, C=O);); elemental analysis calcd (%) for C17H19NO3:
C71.56, H 6.71, N 4.91; found: C71.42, H 6.86, N 4.74.
a
,
0.71073 ä). The cell parameters were determined from reflections
taken from one set of ten frames (1.08 steps in phi angle), each at
20 s exposure. The structure was solved using direct methods
(SIR97) and refined against F2 using the SHELXL97 software. The
absorption was not corrected. All non-hydrogen atoms were refined
anisotropically. Hydrogen atoms were generated according to ster-
Acknowledgments
We are grateful to the Centre National de la Recherche Scientifique for
financial support and the Ministõre de l×Education Nationale, de l×En-
seignement Supÿrieur et de la Recherche for a PhD grant to J.-p.T. and a
post-doctoral grant to Q.-Z.Y. We are also grateful to Prof. R. Welter
(ULP Strasbourg) for the crystal structure determination.
eochemistry and refined using
a riding model in SHELXL97.
CCDC-236259 contains the supplementary crystallographic data
(excluding structure factors) for this paper. These data can be ob-
tained free of charge via www.ccdc.cam.ac.uk/conts/retrieving.html
(or from the Cambridge Crystallographic data Centre, 12 Union
Road, Cambridge CB2 1EZ, UK (fax: (+)(1223)336 033; or deposit@
ccdc.cam.ac.uk).
[1] S. PataÔ, Z. Rappoport, The Chemistry of the quinonoid compounds,
Vol. 1, Wiley, New York, 1988.
[2] P. Stahl, L. Kissau, R. Matzischek, A. Giannis, H. Waldmann,
Angew. Chem. 2002, 114, 1222; Angew. Chem. Int. Ed. 2002, 41,
1174.
[20] O. Siri, P. Braunstein, Chem. Commun. 2000, 2223.
[21] O. Siri, P. Braunstein, M.-M. Rohmer, M. Bÿnard, R. Welter, J. Am.
Chem. Soc. 2003, 125, 13793.
[3] T. Ling, E. Poupon, E. J. Rueden, S. H. Kim, E. A. Theodorakis, J.
Am. Chem. Soc. 2002, 124, 12261.
Received: March 15, 2004
Published online: June 21, 2004
Chem. Eur. J. 2004, 10, 3817 3821
www.chemeurj.org
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3821