Mendeleev Commun., 2012, 22, 67–69
Table 2 Nitration of alcohols and polyols using procedures A and B.a
Isolated yield of 2 (%)
in CO2 (procedure B). The yields of nitrate esters 2a–j prepared
in this way were 3–11% higher than attained by the procedure A
(Table 2). Unavailable by the procedure A pentaerythritol tetra-
nitrate 2k and d-mannitol hexanitrate 2l were readily generated in
91–94% yields under proposed conditions.
In summary, an efficient procedure for O-nitration of alcohols
by a dinitrogen pentoxide/carbon dioxide liquid system has been
proposed. Due to a high heat capacity (Cp 6.35 J g–1 K–1 at 25°C
and a pressure of 64 bar,19 cf. for dichloromethane Cp 1.70 J g–1 K–1
at 20°C20), carbon dioxide effectively consumes the heat of exo-
thermic nitration reaction and prevents uncontrollable processes
to occur. Active ingredients 2j,k,l of pharmaceuticals for curing
cardiovascular diseases21 have been synthesized in high yields
by the developed method.
Starting
alcohol
Nitric
ester
n
Procedure A Procedure B
n-Butanol 1a
2a
2b
2c
2d
1
1
1
1
91
85
90
87
94
91
97
90
Butan-2-ol 1b
n-Hexanol 1c
Cyclohexanol 1d
3-Methyl-3-oxetanemethyl
alcohol 1e
2e
2f
2g
2h
2i
2j
2k
2l
1
2
2
2
2
3
4
6
—
85
—
—
—
95
—
—
95
96
89
93
98
98
94
91
Ethylene glycol 1f
1,3-Propylene glycol 1g
1,4-Butylene glycol 1h
Diethylene glycol 1i
Glycerol 1j
Pentaerythritol 1k
d-Mannitol 1l
This work was supported by the Russian Foundation for Basic
Research (grant no. 11-03-12163-ofi_m).
a The reactions were carried out using an alcohol (8.0 mmol), N2O5 (8.8–
52.8 mmol) at 60–80 bar and 0°C for 30 min.
References
1 (a) T. Urbánski, Chemistry and Technology of Explosives, Pergamon Press,
Oxford, 1965, vol.2; (b) R. Mayer, Explosives, 5th edn. (electronic),
Wiley-VCH Verlag, GmbH, 2002.
2 (a) J.Ahlner, R. G.Andersson, K. Torfgard and K. L.Axelsson, Pharmacol.
Rev., 1991, 43, 351; (b) K. Lange, A. Koenig, C. Roegler, A. Seeling and
J. Lehmann, Bioorg. Med. Chem. Lett., 2009, 19, 3141; (c) M. H. Litchfield,
J. Pharm. Sci., 2006, 60, 1599; (d) G. Wang and Q. L. Lu, US Patent
2011130455, 2011.
comparable with those reported in the literature4(e),7(e),8(d),(e)
(Table 2, procedure A). Corresponding polynitrates 2f,j were
synthesized from polyols 1f and 1j in the presence of 2.2 or
3.3 equiv. of N2O5, respectively. However, the procedure A was
not suitable to the nitration of poorly soluble in liquid CO2 penta-
erythritol 1k and d-mannitol 1l. Moreover, an excessive amount
of nitrating agent at the reaction start may make the procedure
explosion-risky in scaling-up experiments.
3 (a) D. O’Meara and D. M. Shepherd, J. Chem. Soc., 1955, 4232; (b) J. Dewar
and G. Fort, J. Chem. Soc., 1944, 492.
4 (a) R. Boschan, R.W. Van Dolah and R. T. Merrow, Chem. Rev., 1955,
55, 485; (b) J. Honeyman and J. W. W. Morgan, Adv. Carbohydr. Chem.,
1957, 12, 117; (c) G. V. Oreshko and L. T. Eremenko, Izv. Akad. Nauk
SSSR, Ser. Khim., 1989, 1107 (Bull. Acad. Sci. USSR, Div. Chem. Sci.,
1989, 38, 1003); (d) J. P. Agrawal, Mehilal, S. H. Sonawane and R. N.
Surve, J. Hazard. Mater., 2000, 77, 11; (e) G. A. Olah, R. Malhotra and
S. C. Narang, Nitration: Methods and Mechanisms, VCH Publishers,
New York, 1989.
5 (a) H. J. Cook, S. M. David and F. Kaufman, J. Am. Chem. Soc., 1952,
74, 4997; (b) A. Chaney, G. H. McFadden and M. L. Wolfrom, J. Org.
Chem., 1960, 25, 1079; (c) H. Laurent, G. Snatzke and R. Wiechert,
Tetrahedron, 1969, 25, 761; (d) F. E. Behr and R. D. Campbell, J. Org.
Chem., 1973, 38, 1183; (e) N. Hussain, D. O. Morgan, J. A. Murphy and
C. R. White, Tetrahedron Lett., 1994, 35, 5069; (f) J. H. Johnson Jr. and
K.V. Rao, Tetrahedron Lett., 1998, 39, 4611.
6 (a) Yu. V. Guk, M. A. Ilyushin, E. L. Golod and B. V. Gidaspov, Usp.
Khim., 1983, 52, 499 (Russ. Chem. Rev., 1983, 52, 284); (b) J. H. Ridd
and T. Yoshida, in Industrial and Laboratory Nitrations, ACS Symposium
Series 22, eds. L. F. Albright and C. Hanson, American Chemical Society,
Washington, DC, 1976, ch. 6; (c) G. A. Olah, in Chemistry of Energetic
Materials, eds. G. A. Olah and D. R. Squire, Academic Press, New York,
1991, ch. 7.
7 (a) W. R. Feldman and E. H. White, J. Am. Chem. Soc., 1957, 79, 5832;
(b) G. B. Bachman and N. W. Connon, J. Org. Chem., 1969, 34, 4121;
(c) W. E. Elias and L. D. Hayward, Tappi J., 1958, 41, 246; (d) P. Golding,
R. W. Millar, N. C. Paul and D. H. Richards, Tetrahedron Lett., 1988,
29, 2731; (e) P. Golding, R. W. Millar, N. C. Paul and D. H. Richards,
Tetrahedron, 1993, 49, 7037; (f) P. Golding, R. W. Millar, N. C. Paul
and D. H. Richards, Tetrahedron, 1993, 49, 7051; (g) R. W. Millar, M.
E. Colclough, A. W. Arber, R. P. Claridge, R. M. Endsor and J. Hamid,
in Energetic Materials: Chemistry, Hazards and Environmental Aspects,
eds. J. R. Howell and T. E. Fletcher, Nova Science Pub. Inc., New York,
2010.
To overcome these problems, we examined a reverse mode of
components mixing, gradually pressurizing the N2O5/CO2 liquid
system to a stirred solution (emulsion or suspension) of an alcohol
Cyclohexyl nitrate 2d: bp 78–79°C/18 Torr (lit.,8(d) 52–53°C/3 Torr),
nD20 1.4546 (lit.,16 1.4560). IR (NaCl, n/cm–1): 1628 (NO2as), 1264 (NO2 ).
s
1H NMR (CDCl3) d: 4.98–4.90 (m, 1H, CHONO2), 1.99–1.94 (m, 2H,
CH2), 1.81–1.72 (m, 2H, CH2), 1.58–1.24 [m, 6H, (CH2)3]. 13C NMR
(CDCl3) d: 82.38, 29.81, 25.02, 23.52.
3-Methyl-3-(nitroxymethyl)oxetane 2e: bp 39°C/4 Torr, nD20 1.4486. IR
s
(NaCl, n/cm–1): 1634 (NO2as), 1270 (NO2 ). 1H NMR (CDCl3) d: 4.60 (s,
2H, CH2ONO2), 4.51 (d, 2H, CH2O, J 6.2 Hz), 4.42 (d, 2H, CH2O, J 6.2
Hz), 1.39 (s, 3H, Me). 13C NMR (CDCl3) d: 79.24, 77.14, 38.55, 20.91.
Ethylene glycol dinitrate 2f: bp 71–72°C/4 Torr (lit.,16 63–64°C/1.5 Torr)
,
nD20 1.4475 (lit.,16 1.4480). IR (NaCl, n/cm–1): 1640 (NO2as), 1270 (NO2 ).
s
1H NMR (CDCl3) d: 4.76 (s, 4H, CH2ONO2). 13C NMR (CDCl3) d: 68.23.
1,3-Propylene glycol dinitrate 2g: bp 67°C/4 Torr (lit.,16 65°C/1 Torr),
nD20 1.4485. IR (NaCl, n/cm–1): 1633 (NO2as), 1268 (NO2 ). 1H NMR (CDCl3)
s
d: 4.58 (t, 4H, CH2ONO2, J 6.1 Hz), 2.23–2.13 (m, 2H, CH2). 13C NMR
(CDCl3) d: 68.86, 24.89.
1,4-Butylene glycol dinitrate 2h: bp 104–105°C/4 Torr (lit.,17 89–90°C/
2 Torr), n2D0 1.4515. IR (NaCl, n/cm–1): 1621 (NO2as), 1260 (NO2 ). 1H NMR
s
(CDCl3) d: 4.50 (s, 4H, CH2ONO2), 1.88 (s, 4H, CH2). 13C NMR (CDCl3)
d: 72.19, 23.37.
Diethylene glycol dinitrate 2i: bp 132°C/4 Torr (lit.,17 94–95°C/1 Torr),
nD20 1.4525. IR (NaCl, n/cm–1): 1636 (NO2as), 1281 (NO2 ). 1H NMR (CDCl3)
s
d: 4.61 (t, 4H, CH2ONO2, J 4.4 Hz), 3.78 (t, 4H, CH2O, J 4.5 Hz). 13C NMR
(CDCl3) d: 71.87, 67.45.
Glyceryl trinitrate (nitroglycerin) 2j: bp 141–142°C/4 Torr (lit.,16 108–
110°C/1 Torr), nD20 1.4725 (lit.,16 1.4730). IR (NaCl, n/cm–1): 1640
(NO2as), 1270 (NO2 ). 1H NMR (CDCl3) d: 5.57–5.51 (m, 1H, CHONO2),
s
8 (a) G. A. Olah, J. A. Olah and N. A. Overchuk, J. Org. Chem., 1965, 30,
3373; (b) C. A. Cupas, S. C. Narang, G. A. Olah, J. A. Olah and R. L.
Pearson, J. Am. Chem. Soc., 1980, 102, 3507; (c) G. H. Hakimalahi,
A. Khalafi-Nehzad, H. Sharghi and H. Zarrinmayeh, Helv. Chim. Acta,
1984, 67, 906; (d) X.-Y. Li, G. A. Olah, G. K. Surya Prakash and Q. Wang,
Synthesis, 1993, 207; (e) C. A. Cupas, S. C. Narang, G. A. Olah and R. L.
Pearson, Synthesis, 1978, 452; (f) L. Castedo, C. F. Marcos, M. Monteagudo
and G. Tojo, Synth. Commun., 1992, 22, 677.
4.84 (dd, 2H, CH2ONO2, JAA 13.0 Hz, JAB 3.8 Hz), 4.68 (dd, 2H, CH2ONO2,
JAA 13.0 Hz, JAB 5.9 Hz). 13C NMR (CDCl3) d: 74.75, 68.12.
P
entaerythritol tetranitrate 2k: mp 141–142°C (lit.,2(b) 142.2°C). IR (KBr,
s
n/cm–1): 1658 (NO2as), 1288 (NO2 ). 1H NMR (DMSO-d6) d: 4.70 (s, 8H,
CH2ONO2). 13C NMR (CDCl3, 75 MHz) d: 70.30, 40.86.
d-Mannitol hexanitrate 2l: mp 111–112°C (lit.,18 112°C). IR (KBr,
n/cm–1): 1658 (NO2as), 1273 (NO2 ). 1H NMR (CDCl3) d: 6.18–6.08 (m,
s
9 J. P. Agrawal, Chemical World, 2006, 5, 40.
10 M. B. Talawar, R. Sivabalan, B. G. Polke, U. R. Nair, G. M. Gore and
S. N. Asthana, J. Hazard. Mater., 2005, B124, 153.
2H, CHONO2), 6.07–5.97 (m, 2H, CHONO2), 5.12 (dd, 2H, CH2ONO2,
JAA 13.1 Hz, JAB 3.2 Hz), 4.91 (dd, 2H, CH2ONO2, JAA 13.1 Hz, JAB 5.7 Hz).
13C NMR (DMSO-d6) d: 77.12, 76.70, 68.79.
– 68 –