626 J. CHEM.

RESEARCH (S), 2003

SHORT PAPER J. Chem. Research (S),

A simple and efficient method for the N-nitrosation

Province, P.R. China

P.R. China

Secondary amines can be easily converted into their corresponding nitroso derivations using NaNO2–Ac2O as a
nitrosating agent in dichloromethane at room temperature with high yields.

Keywords: N-nitrosation, secondary amines, NaNO2–Ac2O

N-Nitrosation of secondary amines is very important in organic Table 1 N-Nitrosation of Ph2NH with different molar ratio of
synthesis. Some nitroso compounds are widely produced in NaNO2–Ac2O
industry. Various nitrosating agents have been reported, such as, Entry Ph2NH : NaNO2:Ac2O Time/h Yield/%
the most general, nitrous acid, generated from sodium nitrite
and mineral acid in water or in mixed alcohol-water solvents,1 1 1 1 1 1.5 45
nitrosyl salts,2 alkyl nitrites,3 dinitrogen tetroxide,4 2 1 1.5 1.5 1.5 55
oxyhyponitrite,5 Fremy’s salt,6 N-haloamides and sodium nitrite 3 1 2 2 1.5 90
4 1 2.5 2.5 1.5 95
under phase-transfer conditions,7 bis(triphenylphosphine) 5 1 3 3 1.5 98
ammonium nitrite,8 solid acids (i.e. oxalic acid dihydrate,9 6 1 3.5 3.5 1.5 96
inorganic acidic salts10 and hydrolysable chloride salts11) and
sodium nitrite, [NO+. Crown. H (NO3)2-],12 and silica chloride/
NaNO2 Ac2O
NaNO2.13 R1 R2 NH R1R2N N O
CH2Cl2 , r.t.
We wished to develop a new nitrosating agent. In the course
of our study on the oxidation of aryl substituted
semicarbazides to aryl azo compounds with NaNO2–Ac2O,14 Scheme 1
we found the generation of NO+ in this oxidation system. It is
well known that the nitrosating key is the generation of NO+ Table 2 N-Nitrosation of secondary amines using
in the nitrosating reaction. Therefore, we evaluated NaNO2–Ac2O as the nitrosating agent
NaNO2–Ac2O as the nitrosation agent for secondary amines. Entry R1 R2 Time/h Yield/%
In our experiment, we selected Ph2NH as a model. The
optimum molar ratio was sought by using Ph2NH (1 mmol) 1 Me Me 1 91
2 Et Et 1 94
with different molar ratios of NaNO2: Ac2O. The optimum 3 iso-Pr iso-Pr 1.5 93
molar ratio (NaNO2: Ac2O) (3: 3) is required for the most 4 Butyl Butyl 1.5 94
excellent yields. The results are summarised in Table 1.
All reactions were performed smoothly in dichloromethane 5 1 96
at room temperature (Scheme 1) and completed with excellent
6 Ph Ph 1.5 98
yields. The results are summarised in Table 2.
7 Ph COCH3 2 86
To conclude, we recommend this simple, efficient method 8 Ph Me 1 89
for the N-nitrosation of secondary amines under mild
conditions with excellent yields. In all cases, reactions can be
washed with dichloromethane (2×8 ml). The solvent was evaporated
monitored by TLC. We believe that the present methodology
from the combined dichloromethane solutions and the N-nitroso
is an important addition to existing methodology. compounds were obtained. If further purification is needed, column
chromatography on silica gel [eluent: acetone/petroleum ether (10:90)]
Experimental gives pure N-nitroso compounds.
Melting points and boiling points were measured using uncorrected Data on products: N-Nitrosodimethylamine: Yellow liquid, b.p.
temperature gauges. Yields refer to isolated pure products. The 154°C/774mm (Lit.15 153°C /774mm); IR (KBr)ν:2970, 1440, 1305,
nitrosation products were characterised by comparison of their 1048; 1H NMR (CDCl3 ) δ:2.93 (s, 3H, CH3), 3.69 (s, 3H, CH3);
melting or boiling points, Anal. Calcd and spectral (IR, 1H NMR). Anal. Calcd for C2H6N2O:C, 32.41;H, 8.16; N, 37.83. Found: C,
A mixture of secondary amine (1 mmol), acetic anhydride (0.306 g, 32.36; H, 8.23; N, 37.88.
3 mmol) and NaNO2 (0.207 g, 3 mmol) in dichloromethane (10 ml) was N-Nitrosodiethylamine: Yellow oil, b.p. 175–177°C (Lit.15 177°C);
vigorously stirred at room temperature. The progress of the reaction IR (KBr)ν: 2973, 1451, 1223, 1058; 1H NMR (CDCl3)δ : 1.12 (t, 3H,
was monitored by TLC. After completion of the reaction, the reaction CH3), 1.44 (t, 3H, CH3), 3.61 (q, 2H, CH2), 4.13 (q, 2H, CH2); Anal.
mixture was filtered, the undesired precipitates were removed and Calcd for C4H10N2O: C, 47.02; H, 9.87; N, 27.43. Found: C, 47.12;
H, 9.80; N, 27.46.
* To receive any correspondence. E-mail: [email protected] N-Nitrosodiisopropylamine: White crystal, m.p. 47–48°C (Lit.15
† This is a Short Paper, there is therefore no corresponding material in 48°C); IR (KBr)ν: 2962, 1466, 1382, 1120; 1H NMR (CDCl3)δ :
J Chem. Research (M). 1.13(d, 6H, 2CH3), 1.51(d, 6H, 2CH3), 2.8-3.4 (m, 2H, 2CH); Anal.
 J. CHEM. RESEARCH (S), 2003 627

Calcd for C6H14N2O: C, 55.33; H, 10.84; N, 21.53. Found: C, 55.18; T.L. Reynold, C. Fuson, D.Y. Curtin and T.C. Morrill.
H,10.89; N, 21.48. The Systematic Identification of Organic Compounds 6th. Ed.
N-Nitrosodibutylamine: Yellow liquid, b.p. 103–104°C /8 mm John Wiley and Sons, 1980, pp.220-223.
(Lit.16 104–105°C /8mm); IR (KBr)ν: 2978, 1449, 1382, 1070; 2 (a) G.A. Olah, Aldrichimica Acta. 1979, 12, 43; (b) H.S. Tasker
1H NMR (CDCl )δ: 0.92 (t, 6H, 2CH ), 1.12–2.13 (m, 8H, 4CH ),
3 3 2 and H.O. Jones, J. Chem. Soc. 1909, 95, 1910.
3.58 (t, 2H, CH2), 4.09 (t, 2H, CH2); Anal. Calcd for C8H18N2O: C, 3 (a) H. Lecher and W. Siefhen, Chem.Ber. 1926, 59, 1314; (b)
60.70; H, 11.47; N, 17.71. Found: C, 60.10; H, 11.58; N, 17.68. H. Lecher and W. Siefhen, Chem.Ber. 1926, 59, 2594.
N-Nitrosopyrrolidine: Yellow oil, b.p. 213°C (Lit.15 214°C); IR 4 N.N. Makhora, G.A. Karpov, A.N. Mikhailyuk, A.E. Bova,
(KBr)ν: 2983, 1445, 1305, 1202; 1H NMR (CDCl3) δ: 2.10 (m, 4H, L.I. Khmel’nitskii and S.S. Novikov, lzv. Akad.Nauk SSSR, Ser.
2CH2), 3.51 (t, 2H, CH2), 4.23 (t, 2H, CH2); Anal. Calcd for C4H8N2O: Khim. 1978, 1, 226.
C, 47.96; H, 8.06; N, 27.99. Found: C, 47.86; H, 7.98; N, 28.12. 5 S.K. Chang, G.W. Hrrington, M. Rothstein, W.A. Shergalis,
N-Nitrosodiphenylamine: Yellow crystal, m.p. 65–66°C (Lit.15 D. Swern, S.K. Vohra, Cancer Res. 1979, 39, 3871.
66.5°C); IR (KBr)ν: 3070, 1470, 1040, 748, 690; 1H NMR (CDCl3) 6 L. Castedo, R. Riguera and M.P. Vázquez, J. Chem. Soc. Chem.
δ: 7.02–7.56 (m, 10H, 2C6H5); Anal. Calcd for C12H10N2O: C, 72.69; Commun. 1983, 301.
H, 5.09; N, 14.14. Found: C, 72.72; H, 5.02; N, 14.21. 7 M. Nakajima, J.C. Warner, J.P. Anselme, Tetrahedron Lett. 1984,
N-Nitrosoacetanilide: Yellow needles, m.p. 51–52°C (Lit.15 51°C); 25, 2619.
8 J.C. Fanning, L.K. Keefer, K. Larry, J. Chem. Soc. Chem.
IR (KBr)ν: 3050, 2980, 1790, 1455, 760, 701; 1H NMR (CDCl3)δ: 2.06
Commun. 1987, 955.
(s, 3H, CH3), 7.01–7.65 (m, 5H, C6H5); Anal. Calcd for C8H8N2O2:
9 M.A. Zolfigol, Synth. Commun. 1999, 29, 905.
C, 58.51; H, 4.92; N, 17.07. Found: C, 58.45; H, 5.02; N, 17.14. 10 M.A. Zolfigol, E. Ghaemi, E. Madrakian, M. Kiany-Borazjani,
N-Methyl-N-nitrosoaniline:Yellow oil, b.p. 129°C /19 mm (Lit.15 Synth. Commun. 2000, 30, 2057.
128–128.4°C /19mm); IR (KBr)ν: 3070, 2973, 1595, 1450, 1091, 11 M.A. Zolfigol, F. Shirini, A. Ghorbani Choghamarani,
758, 704; 1H NMR (CDCl3) δ: 3.40 (s, 3H, CH3), 7.18–7.55 (m, 5H, A. Taqiannasab, H. Keypour, S. Salehzadeh, J. Chem. Res. (S)
C6H5); Anal. Calcd for C7H8N2O: C, 61.73; H, 5.92; N, 20.59. Found: 2000, 420.
C, 61.43; H, 6.01; N, 20.54. 12 M.A. Zolfigol, M.H. Zebarjadian, G. Chehardoli, H. Keypour,
S. Salehzadeh and M. Shamsipur, J. Org. Chem. 2001, 66, 3619.
Received 18 January 2003; accepted 4 July 2003 13 M.A. Zolfigol, F. Shirini, A.G. Choghamarani, Synth. Commun.
Paper 03/1739 2002, 32, 1809.
14 X.CH. Li, Y.L. Wang, J.Y. Wang, J. Chem. Res. (S) 2002, 284.
15 I. Heilbron and H.M. Bunbury, Dictionary of Organic
References Compounds, London, 1953
1 (a) Vogels Text Book of Practical Organic Chemistry 4th. 16 NMR spectra, Sadlter Research Laboratories, Inc., 1974, 28–30,
Ed, Longman, London and New York 1986; (b) R.L. Sheriner, 19135M.