Electrophilic reaction of nitric oxide with Wittig reagents

Article abstract of DOI:10.1016/j.tetlet.2004.12.087

Reaction of nitric oxide (NO) with p-substituted benzyl triphenylphosphonium chlorides or bromides (Wittig reagents) in CH ₂Cl₂ under argon undergoes electrophilic attack of NO on the carbon center of phosphonium ylides, producing be

Full text of DOI:10.1016/j.tetlet.2004.12.087

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 1095–1097
Electrophilic reaction of nitric oxide with Wittig reagents
Zhongquan Liu, Bo Zhou, Zhongli Liu and Longmin Wu*
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
Received 22 July 2004; revised 6 October 2004; accepted 20 December 2004
Available online 11 January 2005
Abstract—Reaction of nitric oxide (NO) with p-substituted benzyl triphenylphosphonium chlorides or bromides (Wittig reagents) in
CH
2 2
Cl under argon undergoes electrophilic attack of NO on the carbon center of phosphonium ylides, producing benzonitriles.
ꢀ
2004 Elsevier Ltd. All rights reserved.
1
Increasing interest in NO in biological systems pro-
moted us to perform a research project designed to
investigate the chemical behaviors of NO. In general,
the chemistry of NO has been learned in two categories:
free radical and oxidant. As a radical species, it reacts
We let the strong nucleophilic p-substituted benzyl tri-
phenylphosphonium ylides (Wittig reagents) react with
NO and benzonitriles were obtained. We believe that
the reactions most probably proceed on an electrophilic
reaction of NO with the carbon center of ylides.
2
rapidly with other radicals. NO can be oxidized to
3
the nitrosonium or reduced to the nitroxyl anion. Re-
cently, we reported that reaction of epoxides with NO
In a representative experiment, a 15 mL CH Cl solu-
2
2
tion of (p-nitrobenzyl)triphenylphosphonium bromide
(1b) (1 mmol) was thoroughly deaerated by bubbling
argon through for about 30 min. A 3 mL via the same
way deaerated of aqueous solution of sodium hydroxide
(25%) was then slowly added under Ar and stirring.
NO was immediately passed through the mixed solution
for ca. 5 h at room temperature. The total amount of
NO passing through the solution was estimated to be
roughly 100 mmol at the local atmosphere pressure
using the ideal gas law. Preparation, purification, and
transportation of NO were carried out under an argon
atmosphere. The mixture was then extracted with
three 10 mL portions of ether. The ethereal extract
was washed with 3 · 10 mL of water. Afterwards, the
organic phase was dried with magnesium sulfate over
night. Product identification indicates the formation of
4
obtained the corresponding ring-opened products.
The aromatization of Hantzsch dihydropyridines and
the deamination of aromatic primary amines by the
reaction of substrates with NO exhibit the oxidative
reactivity of NO, particularly in the presence of a cata-
lytic amount of oxygen. Although the electrophilic
reactions of NO are very rare, they have been observed
for a long time. Reaction of amides with NO seems to
undergo an electrophilic reaction. The rapid reaction of
NO with O2 yields peroxynitrite and the diffusion-con-
5
,6
7
Àꢀ
8
2
c
trolled reaction of NO with radical anions imply the
electrophilic property of NO, although it is considered
to possess some negative charge character on its nitro-
9
gen. In fact, the synthetic investigation of the clear elec-
1
0
trophilic reaction of NO started from JosephÕs work.
Traube found that NO reacted with enolate anions
1
1
12
p-nitrobenzonitrile (2b), p-nitrotoluene (3b) and tri-
phenylphosphine oxide (Ph P@O) (Scheme 1). IR
to produce compounds with N O bound to nitrogen.
2
2
3
-
X
NO
+
Ph3P H2C
R
R
CN + O PPh3 + R
CH3
NaOH, CH2Cl2
rt, Ar
(
X=CI, Br)
3
1
2
Scheme 1.
Keywords: Electrophilic reaction; Nitric oxide; Wittig reagents.
*
Corresponding author. Tel.: +86 931 8912500; fax: +86 931 8625657; e-mail: nlaoc@lzu.edu.cn
0
040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.12.087

1096
Z. Liu et al. / Tetrahedron Letters 46 (2005) 1095–1097
identification of the residual compounds in the aqueous
phase presented the generation of sodium nitrite (KBr, m
NO 1269 cm ) in the reaction. The experimental re-
by deprotonation of phosphonium salts in the presence
of a strong base, giving a betaine-like zwitterionic 4
shown in Scheme 2. An oxaphosphetane-like four-mem-
bered ring (5 in Scheme 2) in a species and lastly the open-
ing of the four-member ring occurs, generating two frag-
ments, one with a phosphorus–oxygen double bond, that
À
À1
2
sults are summarized in Table 1. The solvent effect on
product yields was investigated using 1b as a substrate.
The yields listed in Table 2 suggest that (1) aprotic sol-
vents such as CCl , CH Cl are greatly favorable for
1
3
is, Ph P@O and the other with a carbon–nitrogen double
4
2
2
3
the formation of benzonitriles; (2) solubility of Wittig re-
agents is another key factor of influencing the yield of 2.
bond, that is, phenylimino radical (6 in Scheme 2). In the
1
4
past several decades, Ingold and co-workers had done
embedded work focus on such imino radicals. As a result,
nitriles were obtained as a major product during these
On the basis of our experimental results, we believe that
the reaction of NO with Wittig reagents most likely
undergoes an electrophilic reaction of NO with the car-
bon center of phosphonium ylides, which are formed
1
5
courses. The byproduct, toluene (3), is directly formed
1
2
from the Wittig reagent under alkaline conditions. In
conclusion, we describe a novel reaction of NO with
Wittig reagents to give nitriles and it was considered to
attribute to the electrophility of NO.
Table 1. Formation of benzonitriles and toluenes from the reaction of
NO with Wittig reagents in CH
2
Cl
2
under an Ar atmosphere
a
Yield of 2 (%)
a
Yield of 3 (%)
Entry
Wittig
reagent
R
Acknowledgements
1
2
3
4
5
6
1a
1b
1c
1d
1e
1f
H
80
95
55
78
65
72
15
5
We thank The National Natural Science Foundation of
China (Research Grant 20272022) for the financial sup-
port. We thank Dr. Botao Fan of University Paris 7 for
the molecule calculation.
NO
Cl
2
40
20
32
25
CN
OC
2 5
H
CH
3
a
Products were characterized by GC-MS.
References and notes
Table 2. Solvent effect on the reaction of NO with 1b
1
2
. (a) Murad, F. Angew. Chem., Int. Ed. 1999, 38, 1856; (b)
Furchgott, R. F. Angew. Chem., Int. Ed. 1999, 38, 1870; (c)
Ignarro, L. J. Angew. Chem., Int. Ed. 1999, 38, 1882; (d)
Pfeiffer, S.; Mayer, B. Angew. Chem., Int. Ed. 1999, 38,
Solvent
CCl
CH
CHCl
Yield of 2 (%)
Yield of 3 (%)
4
98
95
40
60
35
45
Trace
5
60
2
Cl
2
1
714.
3
a
. (a) Janzen, E. G.; Wilcox, A. L.; Manoharan, V. J. Org.
Chem. 1993, 58, 3597; (b) Wilcox, A. L.; Janzen, E. G. J.
Chem. Soc., Chem. Commun. 1993, 1377; (c) Czapski, G.;
Holcman, J.; Bielski, B. H. J. J. Am. Chem. Soc. 1994, 116,
11465; (d) Rockenbauer, A.; Elek, G. Magn. Reson. Med.
DCE
CH CN
Benzene
38
65
3
55
b
THF
30
70
1
995, 6, 352.
c
DMSO
Trace
Trace
3
. Stamler, J. S.; Signel, D. J.; Losacalzo, J. Science 1992,
258, 1898.
a
b
c
1
,2-Dichloroethane.
Tetrahydrofuran.
Dimethylsulfoxide.
4. Liu, Z. Q.; Li, R.; Yang, D. S.; Wu, L. M. Tetrahedron
Lett. 2004, 45, 1565.
NaX +
R
CH3
+
Ph3PO
NaOH
3
+
R
CH2P Ph3
-
X
NaOH
H2O+NaX
1
NO, Ar
H
H
R
C
PPh3
O
R
C
PPh3
O
.N
.
N
4
R
CH PPh3
.
N
O
5
R
CN
R
O PPh3
CH
N
.
2
6
Scheme 2.

Z. Liu et al. / Tetrahedron Letters 46 (2005) 1095–1097
1097
5
6
7
8
. Itoh, T.; Nagata, K.; Matsuya, Y.; Miyazaki, M.; Ohsawa,
A. J. Org. Chem. 1997, 62, 3582.
. Itoh, T.; Nagata, K.; Okada, M.; Ohsawa, A. Tetrahedron
Lett. 1995, 36, 2269.
. Itoh, T.; Nagata, K.; Matsuya, Y.; Miyazaki, M.; Ohsawa,
A. Tetrahedron Lett. 1997, 38, 5017.
. (a) Blough, N. V.; Zafirou, O. C. Inorg. Chem. 1985, 24,
11. Traube, W. Liebigs Ann. Chem. 1898, 300, 81.
12. Froehnke, F. Angew. Chim. 1950, 3, 291.
13. (a) Johnson, A. W. Ylide Chemistry; Academic: New
York, 1995; (b) Pommer, H. Angew. Chem., Int. Ed. Engl.
1977, 16, 423; (c) Maercker, A. Org. React. 1965, 4, 270;
(d) Bruce, E. M.; Allen, B. R. Chem. Rev. 1989, 89, 863.
14. Griller, D.; Mendenhall, G. D.; Van Hoof, W.; Ingold, K.
U. J. Am. Chem. Soc. 1974, 96, 6068.
3
502; (b) Saran, M.; Michel, C.; Bors, W. Free Radical
Res. Commun. 1990, 10, 221; (c) Huie, R. E.; Padmaja, S.
Free Radical Res. Commun. 1993, 18, 195.
. Janzen, E. G. In Bioradicals Detected by ESR spectros-
copy; Ohya-Nishigushi, H., Packer, L., Eds.; Birkhaeuser:
Basel, 1995; pp 113–142.
15. (a) Ogilvie, J. F. Chem. Commun. 1965, 359; (b) Binkley,
R. W. J. Org. Chem. 1968, 33, 2311; (c) Kamachi, M.;
Kuwata, K.; Murahashi, S. J. Phys. Chem. 1971, 75, 164;
(d) Middleton, W. J. J. Am. Chem. Soc. 1971, 93, 423; (e)
Havel, J. J.; Skell, P. S. J. Org. Chem. 1972, 37, 3744; (f)
Poutsma, M. L.; Ibarbia, P. A. J. Org. Chem. 1969, 34,
2848.
9
1
0. Joseph, A. H.; Aloka, S.; Clifford, G.; Larry, K. K.
Tetrahedron Lett. 1998, 39, 5933.