Bismuth chloride-sodium nitrite: A novel reagent for chemoselective N-nitrosation

Article abstract of DOI:10.1080/00397910802413881

Bismuth(III) chloride-sodium nitrite was used as a mild and efficient reagent for N-nitrosation of various tetrazoles, secondary amines, and amides under ambient conditions. Nitrosation took place chemoselectively at the nitrogen atom, giving corresponding N-nitroso derivatives in good to excellent yield. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802413881

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Bismuth Chloride–Sodium
Nitrite: A Novel Reagent for
Chemoselective N-Nitrosation
Atul C. Chaskar a , Bhushan P. Langi a , Amol
Deorukhkar b & Hrushikesh Deokar a
a C. K. Thakur Research Center, Panvel, Navi
Mumbai, India
b The Institute of Science, Mumbai, India
Version of record first published: 27 Jan 2009.
To cite this article: Atul C. Chaskar , Bhushan P. Langi , Amol Deorukhkar &
Hrushikesh Deokar (2009): Bismuth Chloride–Sodium Nitrite: A Novel Reagent for
Chemoselective N-Nitrosation, Synthetic Communications: An International Journal
for Rapid Communication of Synthetic Organic Chemistry, 39:4, 604-612
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Synthetic Communications1, 39: 604–612, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802413881
Bismuth Chloride–Sodium Nitrite: A Novel
Reagent for Chemoselective N-Nitrosation
Atul C. Chaskar,1 Bhushan P. Langi,1 Amol Deorukhkar,2
and Hrushikesh Deokar1
1C. K. Thakur Research Center, Panvel, Navi Mumbai, India
2The Institute of Science, Mumbai, India
Abstract: Bismuth(III) chloride–sodium nitrite was used as a mild and efficient
reagent for N-nitrosation of various tetrazoles, secondary amines, and amides
under ambient conditions. Nitrosation took place chemoselectively at the nitro-
gen atom, giving corresponding N-nitroso derivatives in good to excellent yield.
Keywords: Bismuth(III) chloride, N-nitrosation, nitrosotetrazoles, nitrosamides,
nitrosamines
INTRODUCTION
Nitrosation is an important and well-established reaction in organic
synthesis. The nitrosation of amines is of particular interest as the corre-
sponding N-nitrosamines obtained are found to be biologically active and
show activities such as vasodilatation, platelet aggregation, inflamma-
tion, and neuronal plasticity.[1] N-Nitrosamines have also been used as
pesticides and additives.[2] The N-nitrosamino group is used in the synth-
esis of various a-amino compounds and as synthetic intermediates with
an NO activating group.[3]
N-Nitroso compounds are generally synthesized by N-nitrosation of
the corresponding NH-containing compound (amine, amide, etc.) by
reaction with nitrosating agents.[4] The most general nitrosating reagent
Received June 11, 2008.
Address correspondence to Atul C. Chaskar, C. K. Thakur Research Center,
Panvel, Navi Mumbai 410206, India. E-mail: achaskar@rediffmail.com
604

Bismuth Chloride–Sodium Nitrite
605
Scheme 1. N-Nitrosation of tetrazoles, amines, and amides.
is nitrous acid formed by reaction of a mineral acid, with sodium nitrite
in water or in a mixture of water and an organic solvent (i.e., EtOH,
CHCl3, etc.).[5] In a strongly acidic medium (pH < 4), the main nitrosat-
ing species are nitrosonium ion, dinitrogen trioxide (N2O3), and nitrosyl
halides.[5] In a basic or neutral medium, nitroprusside[4] and alkyl
nitrites[6] are effective nitrosating agents. Several other nitrosating agents
such as N-methyl-N-nitroso-p-toluenesulfonamide (MNTS),[7] peroxy-
nitrite,[8] Fremy’s salt,[9] Angeli’s salt (oxyhyponitrite N2O32ꢀ [10] nitroso-
)
nium tetrafluoroborate,[11] moist SiO2=NaNO2 in the presence of an acid
(mostly solid acids or inorganic halides),[12] [NOþ-crown-H(NO3)2ꢀ],[13]
and PVP–N2O4,[14] and more recently charcoal impregnated with
N2O4,[15] bis(triphenylphosphine) nitrogen(1þ) nitrite,[16] trichloronitro-
methane,[17] some supramolecular complexes of NOx=NOþ,[18] oxalic acid
dihydrate,[19] silica sulfuric acid, and trichlorocyanuric acid[20] have also
been reported.
Recently, use of BiCl3 as a catalyst in organic synthesis has increased
considerably because of its properties such as mild Lewis acidity, low
cost, relatively nontoxic nature, insensitivity to small amounts of water,
and easy availability. Herein we report the combination of bismuth
(III) chloride–sodium nitrite as a novel and efficient nitrosating agents
for various tetrazoles, sec. Amines, and amides (Scheme 1).
RESULTS AND DISCUSSION
The reactions were carried out by adding bismuth chloride to the stirred
solution of NH-containing compounds and sodium nitrite in dichloro-
methane at room temperature. After removal of the insoluble material
by filtration and evaporation of solvents, N-nitroso compounds were
obtained. In some cases, purification was carried out by using column
chromatography.
Several tetrazoles, secondary amines, and amides were subjected to
the nitrosation reaction by using bismuth chloride–sodium nitrite systems
in dichloromethane at room temperature with good to excellent yields,

606
A. C. Chaskar et al.
and the results are listed in Table 1. To the best of our knowledge,
N-nitroso derivative in entry 1 is unknown in the literature. Physical
and spectral data of known compounds are in agreement with those
reported in the literature.[12]
The method was found to be chemoselective. As in the case of
N-methyl aniline, nitrosation took place selectively at N-H and not on
the aromatic ring (Scheme 2). The actual nitrosating agent may be NOCl,
which is produced in situ by bismuth chloride and sodium nitrite.
CONCLUSION
In conclusion, an efficient, simple, and novel methodology for chemo-
selective N-nitrosation of tetrazoles, amines, and amides is developed.
Relatively short reaction times, utilization of cheap and readily available
reagents, and high yield of products are some of the advantages of the
present protocol. These advantages make the present method useful for
large-scale operations.
EXPERIMENTAL
All commercial reagents were used as received without purification, and
all solvents were reagent grade. The reaction mixture was stirred
magnetically in a round-bottom flask and was monitored by thin-layer
chromatography (TLC) using on 0.25-mm E-Merck silica-gel 60 F254
precoated glass plates, which were visualized with UV light and then
purified by using silica gel, 60–120 mesh. Melting points were taken in
open capillaries. The IR spectra were recorded on a Perkin-Elmer 257
spectrometer using KBr discs. 1H NMR and 13C NMR spectra in
DMSO-d6 were recorded on VXR 300-MHz instrument using TMS as
internal standard, and mass spectra were recorded on a Shimadzu
GC-MS. The characterization data is given below.
N-Nitrosation of 3-(10 H-tetrazol-50-yl)-8-methyl-2H,5H-pyrano[3,2-c]
benzopyran-2,5-dione, a Typical Procedure
To a stirred suspension of sodium nitrite (4.3 mmol) and 3-(10 H-tetrazol-
50-yl)-8-methyl-2H,5H-pyrano[3,2-c]benzopyran-2,5-dione (4.1 mmol) in
CH2Cl2 (15 mL), BiCl3 (4.3 mmol) was added at room temperature.
The reaction mixture was stirred for 40 min. The insoluble solid was
removed by filtration, and the filtrate was concentrated under reduced

Bismuth Chloride–Sodium Nitrite
607
Table 1. N-Nitrosation of tetrazoles, amines, and amides
Isolated
Time yield
(min) (%)
Sr.
no.
Substrate
Product
1
40
89
2
3
35
10
91
97
4
5
20
35
96
99
6
7
40
25
87
90
(Continued )

608
A. C. Chaskar et al.
Table 1. Continued
Isolated
Time yield
(min) (%)
Sr.
no.
Substrate
Product
8
20
88
9
40
78
10
11
30
25
91
87
12
35
87
13
14
70
40
76
87
(HOCH2CH2)2NH
(HOCH2CH2)2N—NO
(Continued )

Bismuth Chloride–Sodium Nitrite
609
Table 1. Continued
Isolated
Time yield
(min) (%)
Sr.
no.
Substrate
Product
15
120
68
16
30
90
17
18
25
50
89
74
19
55
76
20
21
95
90
86
110

610
A. C. Chaskar et al.
Scheme 2. Nitrosation of N-methyl aniline.
pressure to get 3-(10 nitroso-tetrazol-50-yl)-8-methyl-2H,5H-pyrano [3,2-
c]benzopyran-2,5-dione.
Data
IR (KBr): 1720 (>C ¼ O), 1640, 1620, 1516, 1513 (N ¼ O), 1394, 1267,
1
1174, 1071, 871, 791 cmꢀ1. H NMR DMSO-d6 (d ppm): 2.30 (s, 3H,
CH3), 6.70 (s, 1H, C4-H), 7.20 (d, 1H, C9-H, J ¼ 8 Hz), 7.31 (d, 1H,
C10-H, J ¼ 8 Hz), 7.49 (s, 1H, C7-H). 13C NMR DMSO-d6 (d ppm):
20.1 (CH3), 101.5 (C4a), 119.5 (C7), 121.0 (C9), 122.0 (C10), 127.5
(C10a), 129.5 (C4), 132.6 (C8), 152.2 (C6a and C11), 155.3 (N-C ¼ N),
159.1 (C3), 162.1 (C5), 164.5 (C2). Mass m=z (%): 325 (26%) Mþ,
295(43), 277(10), 268(100), 267(69), 240(13), 214(13), 212(7), 190(9),
184(16), 175(23), 161(17), 150(25), 143(20), 137(29), 121(37), 105(35),
91(79), 77(70), 44(62). Elem. anal. calcd: C, 51.69; H, 2.15; N, 21.54;
O, 24.62. Found: C, 51.64; H, 2.19; N, 21.58; O, 24.58.
ACKNOWLEDGMENT
Authors are grateful to acknowledge the financial support from the
University Grant Commission (UGC), New Delhi. The authors are also
thankful to Dr. S. T. Gadade, principal, C. K. Thakur College, for
providing laboratory and other facilities.
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