Highly stereoselective nitration of chalcone derivatives with nitric oxide

Article abstract of DOI:10.1055/s-2006-939700

A novel nitration of chalcone derivatives with nitric oxide affords E-α-nitropropenones exclusively in good yield. The reaction is most likely initiated by electrophilic addition of nitric dioxide to the C=C double bond at the α-position. Georg Thieme Ver

Full text of DOI:10.1055/s-2006-939700

LETTER
1367
Highly Stereoselective Nitration of Chalcone Derivatives with Nitric Oxide
Stereoselective
N
u
itration of
C
i
halcone
D
eriv
L
atives i,a Zhongquan Liu,a,b Yulu Zhou,a Longmin Wu*a
a
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, P. R. of China
b
Academy of Organic Chemistry, Gannan Teachers’ College, Ganzhou, Jiangxi 341000, P. R. of China
Fax +86(931)8625657; E-mail: nlaoc@lzu.edu.cn
Received 19 December 2005
geometry of 2 was well controlled. The nitro group was
located exclusively at the a-position with respect to the
carbonyl group of E-configured chalcone derivates
(Scheme 1).2,10
Abstract: A novel nitration of chalcone derivatives with nitric
oxide affords E-a-nitropropenones exclusively in good yield. The
reaction is most likely initiated by electrophilic addition of nitric
dioxide to the C=C double bond at the a-position.
Key words: stereoselective, nitration, chalcone, nitric oxide, E-2-
nitropropenone
O
H
R
NO2
R'
NO (trace O2)
CH2Cl2
R
R'
O
Introduction of nitrogen-containing functional groups into
organic compounds is one of the important subjects in
synthetic organic chemistry.1 There has been much effort
invested in discovering new methods to effect this trans-
formation, among them, the nitration of olefins is a facile
method for C–N bond formation. Although great progress
has been made in this field, the a-vinylic nitration of a,b-
unsaturated systems has not been well documented so far.
It is particularly noteworthy that the a-vinylic nitration of
a,b-unsaturated systems has elicited wide interest. The re-
sulting a-nitrochalcones are important intermediates in
organic synthesis because of their activated C=C double
bond and their adjacent nitro and carbonyl groups.2
Dorrow3 reported that the condensation of N-benzalbutyl-
amine with w-nitroacetophenone afforded a-nitrochal-
cone in 48% yield. Later, Lehnert modified this procedure
using titanium tetrachloride in anhydrous tetrahydrofuran,
for the condensation of aromatic aldehydes with w-ni-
troacetophenone at a lower temperature, afforded a-nitro-
chalcones in 76% yield.2a,4 Yet, these methods have
suffered from one or more of the following drawbacks:
harsh conditions, expensive reagents, multi-step prepara-
tion of materials, or unsatisfactory yield. As part of our
ongoing research program on the chemistry of nitric oxide
(NO), reactions of NO with arylhydrazones,5 epoxides,6
1
2
R = Ar, R' = Ar or Me
Scheme 1
It is well known that NO is a highly stable free radical. It
neither abstracts a hydrogen atom nor adds to an unacti-
vated double bond, but it can couple with other radicals.
NO2 is appreciably more reactive than NO and reacts pre-
ferentially with dienes.11 In the present case, a trace of
oxygen oxidizes NO to NO2, then electrophilic addition of
NO2 to the double bond of the chalcone derivative occurs
selectively at the a-position with respect to its carbonyl
group to give a carbon-centered radical 3 (Scheme 2).
Coupling of NO with the b-carbon of 3 takes place afford-
ing nitroso compound 4. Addition of two equivalents of
NO to the nitroso group of 4 gives an N-nitroso-N-nitrite
511 which rearranges to diazonium nitrate 6. Finally, the
intermediate 6 undergoes anti-elimination to give the final
product 2. No reaction occurred when the system was
completely protected from air. Attempted nitration of
chalcones with NO2 led to very complicated reaction mix-
tures. Therefore, a trace of oxygen is considered to initiate
the reaction via NO2. At the very beginning of the reac-
tion, oxygen oxidizes NO to NO2, which then initiates the
reaction. Once the reaction is initiated, the NO2 required
afterward comes from the reaction of NO with HNO3,11
which is produced during the elimination (Scheme 2),
rather than from NO and O2. An excess of NO2 will react
with the intermediates to give many byproducts.12 Actual-
ly, the coupling of NO with the intermediate 3 is diastere-
oselective because both possible diastereomers may be
stable. The formation of the E-2-nitropropenone, ex-
clusively, is most likely attributed to the energetically
favorable anti-elimination and the higher stability10 of the
E-isomer with respect to the Z-isomer.
8
aziridines,7 and Wittig reagent were studied. Our inter-
ests in NO have prompted us to perform the nitration of
chalcone derivatives with NO. In this communication, we
will report a novel approach to a-nitrochalcones.
In a typical experiment,9 the reaction of chalcone deriva-
tive 1 with NO was carried out at ambient temperature,
which was initiated by nitric dioxide (NO2), and gave the
single mono-nitration product, E-2-nitropropenone (2),
with yields ranging from 73% to 90% (Table 1). Spectral
data (1H and 13C NMR, MS, HRMS, IR,9 1D NOE,
HMQC, and HMBC) obtained for 2 indicated that the
The results listed in Table 1 seem to indicate roughly that
an electron-donating substituent at the para-position of
the phenyl ring (R) in 1 leads to a higher yield as can be
seen for 1d and 1e. It may be attributed to the electron-
SYNLETT 2006, No. 9, pp 1367–1368
Advanced online publication: 22.05.2006
DOI: 10.1055/s-2006-939700; Art ID: W11405ST
© Georg Thieme Verlag Stuttgart · New York
0
1.
0
6.
2
0
0
6

1368
R. Li et al.
LETTER
O
References and Notes
COR'
NO2
COR'
NO2
H
H
R
R
NO (O2)
R'
NO
2 NO
.
(1) (a) Kabalka, G. W.; Varma, S. R. Org. Prep. Proced. Int.
1987, 19, 283. (b) Barrett, A. G. M. Chem. Soc. Rev. 1991,
20, 95. (c) Reddy, M. V. R.; Mehrotra, B.; Vankar, Y. D.
Tetrahedron Lett. 1995, 36, 4861.
(2) (a) Mélot, J. M.; Texier-Boullet, F.; Foucaud, A.
Tetrahedron 1988, 44, 2215. (b) Ciller, J. A.; Seoane, C.;
Soto, J. L. J. Hetreocycl. Chem. 1985, 22, 1663. (c) Boger,
D. L.; Lerner, R. A.; Cravatt, B. F. J. Org. Chem. 1994, 59,
5078.
R
H
H
ON
1
3
4
ONO2
COR'
NO2
H
N
N
COR'
NO2
– N2
..
N
N
H
O
2
R
– HNO3
R
N
H
..
O
..
H
O
..
5
6
(3) Dornow, A.; Müller, A.; Lupfer, S. Justus Liebigs Ann.
Chem. 1955, 594, 191.
Scheme 2
(4) Lehnert, W. Tetrahedron 1972, 28, 663.
(5) Yang, D. S.; Lei, L. D.; Liu, Z. Q.; Wu, L. M. Tetrahedron
Lett. 2003, 44, 7245.
(6) Liu, Z. Q.; Li, R.; Yang, D. S.; Wu, L. M. Tetrahedron Lett.
2004, 45, 1565.
(7) Liu, Z. Q.; Fan, Y.; Li, R.; Zhou, B.; Wu, L. M. Tetrahedron
Lett. 2005, 46, 1023.
(8) Liu, Z. Q.; Zhou, B.; Liu, Z. L.; Wu, L. M. Tetrahedron Lett.
2005, 46, 1095.
donating group stabilizing the radical 3 through reso-
nance. Neither the substituents on the phenyl ring (R¢) nor
the replacement of the aryl group with an alkyl group have
any obvious effects on the chemical yields, as shown in
the cases of 1b, 1c, and 1h. This is reasonable when you
consider the large distance between R¢ and the radical
center of the intermediate 3.
(9) Typical Procedure A stock solution was prepared by
dissolving 1a (104 mg, 0.5 mmol) in anhyd CH2Cl2 (100
mL). NO was produced by the reaction of a 1 M H2SO4
solution with a sat. aq solution of NaNO2 under an argon
atmosphere (H2SO4 was added dropwise). NO was carried
by argon and purified by passing it through a series of
scrubbing bottles containing distilled water, 4 M NaOH, and
CaCl2 (in this order; bottles were kept under an argon
atmosphere). Purified NO was bubbled through the stock
solution, which was previously degassed with argon for
6 min. In the course of degassing, the argon flow rate was
controlled by regulating the flow-meter at 0.8 Lmin–1 and the
stock solution was kept at a pressure of up to +10 mm (water
column over local atmospheric pressure at 10 °C). The total
amount of NO was passed through the solution estimated to
be roughly 300 mmol at local atmospheric pressure using the
ideal gas law. After completion of the reaction, as indicated
by TLC, the reaction mixture was dried over anhyd MgSO4,
concentrated under vacuum, and purified by column
chromatography on silica gel (200–300 mesh, EtOAc–PE),
giving pure 2a (98 mg, 78%); mp 92 °C. IR (KBr): 3062,
2923, 1679, 1638, 1522, 1316, 1231, 947, 765, 687 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.35 (m, 2 H), 7.42 (m, 3
H), 7.49 (m, 2 H), 7.63 (m, 1 H), 7.96 (m, 2 H), 8.34 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 128.9, 129.2 (2 C), 129.3,
131.0, 132.3, 133.5, 134.9, 137.3, 144.7, 188.2. MS-EI:
m/z = 253 (M+), 191, 132, 105, 102, 77, 63. HRMS-ESI:
m/z calcd for C15H12NO3: 254.0812; found: 254.0811.
(10) (a) Watarai, S.; Yamamura, K.; Kinugasa, T. Bull. Chem.
Soc. Jpn. 1967, 40, 1448. (b) Yamamura, K.; Watarai, S.;
Kinugasa, T. Bull. Chem. Soc. Jpn. 1971, 44, 2440.
(11) Kelly, D. R.; Jones, S.; Adigun, J. O.; Koh, K. S. V.; Hibbs,
D. E.; Hursthouse, M. B.; Jackson, S. K. Tetrahedron 1997,
53, 17221.
Table 1 Reaction of Chalcone Derivatives with NO at Ambient
Temperature in CH2Cl2
a
Entry
1
R
R¢
2
Yield (%)b
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
Ph
Ph
2a
2b
2c
2d
78
75
76
89
90
82
73
80
Ph
p-FC6H4
p-BrC6H4
Ph
Ph
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-OMeC6H4 2e
p-ClC6H4
2f
1g
1h
p-OMeC6H4 p-BrC6H4
Ph Me
2g
2h
a All reaction times were 15 h.
b Isolated yields after column chromatography.
We have presented a new approach for preparing a-nitro
chalcone derivatives directly from chalcone derivatives
using NO. The main advantages of this methodology are
its high steroselectivity, readily available starting materi-
als, and convenient performance under mild conditions.
We are currently working on extending the scope of the
reaction by broadening both the range of substrates and
nitrogen sources.
(12) Brown, J. F. Jr. J. Am. Chem. Soc. 1957, 79, 2480.
Acknowledgment
Projects 20572040 and 20272022 were supported by the National
Natural Science Foundation of China.
Synlett 2006, No. 9, 1367–1368 © Thieme Stuttgart · New York