Zn(NO3)2·6H2O/2,4,6-trichloro-1,3,5-triazine (TCT) a mild and selective system for nitration of phenols

Article abstract of DOI:10.1016/j.cclet.2009.11.017

Certain phenols and naphthols were nitrated regioselectively with Zn(NO₃)₂·6H₂O/TCT in acetonitrile as solvent at room temperature and short reaction time in good yields. The reaction condition was mild. TCT is a cheap and commercially available reagent. It performed as an acid catalyst in this transformation.

Full text of DOI:10.1016/j.cclet.2009.11.017

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Chinese Chemical Letters 21 (2010) 403–406
www.elsevier.com/locate/cclet
Zn(NO3)2Á6H2O/2,4,6-trichloro-1,3,5-triazine (TCT) a mild and
selective system for nitration of phenols
*
Firouzeh Nemati , Hossein Kiani
Department of Chemistry, Faculty of Science, Semnan University, Semnan, Iran
Received 18 August 2009
Abstract
Certain phenols and naphthols were nitrated regioselectively with Zn(NO3)2Á6H2O/TCT in acetonitrile as solvent at room
temperature and short reaction time in good yields. The reaction condition was mild. TCT is a cheap and commercially available
reagent. It performed as an acid catalyst in this transformation.
# 2009 Firouzeh Nemati. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Nitration; Phenols; 2,4,6-Trichloro-1,3,5-triazine; Regioselective
Nitration of aromatic compounds is an industrially important reaction [1]. They are important intermediates for the
manufacture of drugs and pharmaceuticals. Among these compounds o-nitro phenols and naphthols are important
starting material used in synthesis of valuable compounds [2].
Most phenolic nitration, as classically performed with mixtures of nitric and sulfuric acids, give predominantly
ortho and para products, that their distribution is close to the statically 2:1 ratio [3]. It has remained unchanged in the
commercial area owing to uneconomical alternative options.
Nitration using other acid sources may be the answer to these problems. In recent years different solid acids tested
so far include zeolite-based solid acid catalysts [4], silica supported sulfuric acid [5], p-toluenesulfonic acid [6],
MCM-41 [7], heteropolyacids [8], silica chloride [9], nanosized tungsten oxide supported on sulfated SnO2 [10].
Considering these reactions and with the cause of environmental concerns, there is still a good scope for research
towards finding green and eco-friendly process for regioselective nitration of phenols.
2,4,6-Trichloro[1,3,5]triazine (cyanuric chloride or TCT) is a stable, non-volatile, inexpensive and safe reagent
(Fig. 1) which has been used synthetically for the preparation of various types of compounds [11–15]. We used it as a
dry acid source in Mannich reaction [16]. It is highly soluble in organic solvents, which makes it an ideal catalyst for
organic syntheses. Cyanuric acid (the waste product of this reaction) is a non-hazardous substance and is readily
removable by water.
In this manuscript, we wish to report a regioselective and mild route to the nitration of phenols using
Zn(NO3)2Á6H2O as nitrating agent and 2,4,6-trihloro-1,3,5-triazine (TCT) as acid catalyst (Scheme 1).
* Corresponding author.
E-mail address: fnemati_1350@yahoo.com (F. Nemati).
1001-8417/$ – see front matter # 2009 Firouzeh Nemati. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2009.11.017

404
F. Nemati, H. Kiani / Chinese Chemical Letters 21 (2010) 403–406
Fig. 1. The structure of TCT.
Scheme 1. Nitration phenols using Zn(NO3)2Á6H2O/TCT.
Table 1
Nitration phenol using different metal nitrates in the presence of 2 or 3 mol% TCT in acetonitrile at room temperature.
Entry
Metal nitrates
TCT (mmol)
Time (h)
% o-nitro phenol
1
2
NaNO2
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.03
0.03
18
16
1
60
55
40
55
50
75
75
60
80
60
NaNO3
3
Cr(NO3)3Á9H2O
Fe(NO3)3Á9H2O
Co(NO3)2Á6H2O
Ni(NO3)2Á6H2O
Mn(NO3)2Á4H2O
Bi(NO3)3Á5H2O
Zn(NO3)2Á6H2O
Cu(NO3)2Á3H2O
4
0.5
10
2
5
6
7
3
8
9
9
1.5
7
10
Avariety of metal nitrates in the presence of catalytic amount of TCTwere screened and the results are summarized
in Table 1. Among them Zn(NO3)2Á6H2O was remarkable.
In a typical general experimental procedure, phenolic compound and Zn(NO3)2Á6H2O stirred in acetonitrile in the
presence of a catalytic amount of TCT(3 mol%, 0.03 mmol) for a period of time required to complete the reaction (10–
100 min). The results are summarized in Table 2. All the selected phenols yielded the o-nitro product exclusively in
good to excellent yields.
TCT reacted with incipient moisture and released 3 mol of HCl and cyanuric acid (removable by washing with
water) as by-product [17]. The in situ generated HCl acts as a protic acid and produce NO2+ from the nitrating agent.
Table 3 compares the efficiency of our method with the efficiency of some other works in the nitration of phenols.
Table 2
Nitration of phenols using Zn(NO3)2Á6H2O/TCT in acetonitrile at room temperature.
Entry
Substrate
Products
Time (min)
Yield (%)a
1
2
Phenol
o-Nitro phenol
90
60
80
85
90
65
75
90
85
90
90
90
Naphthalen-1-ol
Naphthalen-2-ol
m-cresol
2-Nitronaphthalen-1-ol
1-Nitronaphthalen-2-ol
5-methyl-2-nitrophenol
4-Nitrobenzene-1,3-diol
2-Hydroxy-3-Nitrobenzaldehyde
2-Chloro-6-nitrophenol
4-Chloro-2-nitrophenol
4-Methyl-2-nitrophenol
4-Hydroxy-3-nitrobenzaldehyde
3
50
4
30
5
Resorcinol
80
6
2-Hydroxybenzaldehyde
2-Chlorophenol
4-Chlorophenol
p-Cresol
100
100
90
7
8
9
10
10
2-Hydroxybenzaldehyde
70
a
Isolated yield.

F. Nemati, H. Kiani / Chinese Chemical Letters 21 (2010) 403–406
405
Table 3
Comparison of results using Zn(NO3)2Á6H2O/TCT with results obtained by other workers for the nitration of phenol.
Nitrating agent/Acid catalyst
Conditions
Time/(h)
Yield (%)a
Ref.
MCM-41/HNO3 30%
WSSnO2b/HNO3
DCE/RT
2
1
90
80
40
41
36
30
93
80
[7]
[10]
[18]
[19]
[20]
[5]
60 8C
ZrO(NO3)2ÁxH2O
Acetone/RT
THF/30 8C
CH2Cl2/RT
CH2Cl2/RT
CHCl3/À20 8C
CH3CN/RT
0.5
12
0.5
1.5
2
Metal modified KSF/HNO3
Mg(HSO4)2/NaNO3/wet SiO2
NaNO2/SSA/Wet SiO2
Acetyl nitrate/SiO2
[21]
–
Zn(NO3)2Á6H2O/TCT
1.5
a
o-Nitro phenol.
b
Nanosized tungsten oxide supported on sulfated SnO2.
In summary, the ortho nitration of phenols with Zn(NO3)2Á6H2O and catalytic amount of TCT has been achieved
with high regioselectivity and excellent yields. The use of inexpensive acid catalyst made this methodology green and
wide synthetic and commercial utility.
1. Experimental
Chemicals were purchased from the Fluka, Merck and Aldrich chemical companies. The nitration products
1
characterized by comparison of their spectral (IR, H NMR), TLC and melting point with authentic samples.
1.1. General procedure for mononitration of phenols
Phenol (0.094 g, 1 mmol), Zn(NO3)2Á6H2O (0.297 g, 1 mmol) and TCT (0.006 g, 0.03 mmol) in 10 mL of
acetonitrile were magnetically stirred at room temperature. After the completion of the reaction, the reaction solvent
dried over anhydrous sodium sulfate. The solvent was removed under vacuum (35–40 8C). The crude product was
purified by silica-gel dry flash chromatography using petroleum ether–ethyl acetate (98:2) as eluent. The yield was
0.11 g (80%), mp 43 8C (Ref. [18] mp 44 8C).
1
1.2. The spectral (IR, H NMR,) and analytical data for 5-methyl-2-nitrophenol (entry4, Table 2)
Mp: 53–54 8C(Ref. [6] mp 53–56 8C); IR (KBr) ymax (cmÀ1): 3249, 1632, 1332, 766.
1H NMR (300 MHz; CDCl3; Me4Si): d 10.75 (s, 1H), 7.79 (d, 1H, J = 8.4 Hz), 6.91 (s, 1H), 6.76 (dd, 1H, J = 8.4,
J = 0.9 Hz), 2.29 (s, 3H).
1
1.3. The spectral (IR, H NMR,) and analytical data for 4-chloro-2-nitrophenol (entry 8, Table 2)
Mp: 89–90 8C (Ref. [5] mp: 89 8C); IR (KBr): ymax/cmÀ1: 3290, 1631, 1484, 850.
1H NMR (300 MHz; CDCl3; Me4Si): d 11.26 (s, 1H), 7.90 (d, 1H, J = 2.6 Hz), 7.55 (dd, 1H, J = 8.9, J = 2.6 Hz),
7.13 (d, 1H, J = 8.94 Hz).
Acknowledgment
We thank the Department of Chemistry of Semnan University for supporting this work.
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