Nitration of arenes by 1-sulfopyridinium nitrate as an ionic liquid and reagent by in situ generation of NO₂

Abstract

1-Sulfopyridinium nitrate was synthesized as a potent nitrating agent for the nitration of arenes without the need for any co-catalysts. A variety of nitro compounds were synthesized and fully characterized by IR, ¹H NMR, ¹³C NMR, thermal gravimetric analysis (TGA), differential thermal gravimetry (DTG), CHN analysis and mass spectroscopy. Mechanistically, in situ generated nitrogen dioxide as a radical from the reagent is proposed for the presented nitration protocol.

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Nitro compounds are one of the principal groups of compounds that have been widely used in organic chemistry and industry.^1–5 Nitro compounds hold many applications such as in high-energy materials, dyes, pharmaceuticals, perfumes, medicine and plastics and also play a significant role in the development of the concept of mechanisms.⁶ Therefore, great attention has been centered on the development of efficient and practical approaches for the synthesis of nitro compounds. The conventional nitration protocols are performed by the use of an excess of nitric acid or a mixture of nitric acid and sulfuric acid or dinitrogen pentoxide. As an alternative, yet efficient procedure, mixtures of nitric acid with aluminum chloride, polyphosphoric acid, perchloric acid, methanesulfonic acid, hydrogen fluoride and superacids such as boron trifluoride, triflic acid, fluorosulfonic acid and many others have been reported.⁷ However, many of the reported approaches are associated with some drawbacks including: low yields, long reaction times, over nitration, the use of a large catalyst loading, low regioselectivity, oxidation of reagents and safety problems.⁸ Therefore, designing an efficient nitration protocol is still of practical importance.

Recently, we reported sulfonic acid functionalized imidazolium salts (SAFIS) as a new class of acidic ionic liquids in which S–N bond has been formed leading to imidazole derivatives, as five-membered heterocyclic compounds. We found these materials have interesting applications as green and eco-friendly solvents, catalysts and reagents in organic transformations.^8–23 In continuation of our previous works, we also recently reported a new category of ionic liquids, namely sulfonic acid-functionalized pyridinium salts. In such systems, S–N bonds are formed and we use them as organocatalysts for the synthesis of bis(pyrazolil)methans,²⁴ xanthene derivatives,²⁵ bis(coumarin)methans,²⁶ and hexahydroquinolines.²⁷

Having above facts and according to our previous work in the field of nitration,⁸ we were interested in the development of green chemistry protocols using new approaches such as the use of ionic liquids to reduce/eliminate co-catalysts and/or solvents. We prepared the ionic liquid 1-sulfopyridinium nitrate and found it is a highly efficient and green reagent without the need of a co-catalyst for the nitration of arenes and alkenes (Fig. 1, Schemes 1 and 2).

Fig. 1 The structure and color of [pyridine–SO₃H]NO₃.

Scheme 1 Preparation of 1-sulfopyridinium nitrate {[pyridine–SO₃H]NO₃}.

Scheme 2 Nitration of aromatic compounds using [pyridine–SO₃H]NO₃.

1-Sulfopyridinium chloride was synthesized by the reaction of pyridine with ClSO₃H according to literature.^24,25 Then, by the reaction of [pyridine–SO₃H]Cl with HNO₃, [pyridine–SO₃H]NO₃ was prepared and characteized by IR, ¹H and ¹³C NMR, mass spectroscopy as well as CHN analysis.

The IR spectrum of the reagent shows two strong peaks at about 1308 cm⁻¹ and 1543 cm⁻¹ which are typical of ν_O–N=O symmetric stretching vibration and ν_O–N=O asymmetric stretching vibration, respectively (Fig. 2). Moreover, two peaks observed at 1183 cm⁻¹ and 1334 cm⁻¹ are related to vibrational modes of N–SO₂ and O–SO₂ bonds and a broad peak at 3100–3600 cm⁻¹ could be signatures of O–H stretching of SO₃H group.

Fig. 2 IR spectrum of 1-sulfopyridinium chloride {[pyridine–SO₃H]NO₃}.

The ¹H NMR spectrum of [pyridine–SO₃H]NO₃ shows the acidic hydrogen (SO₃H) peak at 11.37 ppm (Fig. 2). To confirm that this peak is indeed related to the hydrogen of SO₃H in the compound, we also compared the ¹H NMR spectra of ClSO₃H, [PySO₃H]Cl and pyridinium chloride with HNO₃ in DMSO-d₆. In these spectra, the peaks of the acidic hydrogens of [pyridine–SO₃H]NO₃, ClSO₃H, [pyridine–SO₃H]Cl, pyridinium chloride and HNO₃ were observed at 11.37, 13.45, 13.96, 8.46, and 13.01 ppm, respectively (Fig. 3).^8,24 The mass spectrum of the compound gave the consistent molecular ion peak at 222 m/z.

Fig. 3 The ¹HNMR and ¹³CNMR spectra of the 1-sulfopyridinium nitrate.

The thermogram (TG) of the reagent was studied and showed two main weight losses. The first loss of weight of the reagent was observed during the range of 60 °C to 160 °C, which could be related to loss of NO₂. The second weight loss occurred between 240 °C and 320 °C and the loss after 320 °C is related to molecular decomposition (Fig. 4).

Fig. 4 TG/DTG of the 1-sulfopyridinium nitrate.

In another experiment, the gas (nitrogen dioxide) that was released from [pyridine–SO₃H]NO₃ upon heating at about 60 °C was collected in a test tube, transferred to a round-bottomed flask in the presence of copper powder and ethyl acetate. NO₂ in equilibrium with dinitrogen tetroxide (N₂O₄)²⁸ reacts with copper metal to give Cu(NO₃)₂. In this reaction, appearance of the blue color due to copper nitrate formation in anhydrous media is a convincing evidence of the release of nitrogen dioxide (Fig. 5).^8,29 Additionally, the excess copper powder residue turned black over time, suggesting that O₂ is produced from [pyridine–SO₃H]NO₃ as well. Oxygen reacts with copper metal to form the black copper oxide as an insoluble residue (Scheme 3).

Fig. 5 Preparation of copper nitrate (with blue color, right picture) from copper powder (left picture) as an evidence for the release of nitrogen dioxide.

Scheme 3 The identification of nitrogen dioxide and oxygen using copper powder.

A wide range of compounds including benzene, toluene, o-xylene, naphthalene, anthracene, phenols, anisol, 2-naphthol, anilines, styrene and bromobenzene were also nitrated with [pyridine–SO₃H]Cl (Table 1). By the reaction of [pyridine–SO₃H]NO₃ with benzenethiol and naphthalene-2-thiol the main products were 1,2-diphenyldisulfane and 1-(naphthalen-2-yl)-2-(naphthalen-6-yl) disulfane respectively (Table 1, entries 11 and 14). In this reaction conditions thiols were converted to the corresponding Ar–S˙ radical in the presence of NO₂. Two of these radicals dimerize to give diaryldisulfane and nitrous acid as a byproduct. Nitration of styrene as olefin compound was also studied and only the E isomer was obtained. 1-((E)-2-nitrovinyl)benzene was prepared in 62% yield after three minutes in presented reaction conditions. In our presented method, the regioselective nitration of styrene by 1-sulfopyridinium nitrate is more efficient in compared with previous literature reports (Scheme 4).³⁰

Table 1 Nitration of aromatic and aliphatic compounds by using {[pyridine–SO₃H]NO₃}

Product	Time (min)	Yield^a (%)	m.p/b.p (°C) [ref]
a Yield of purified product.
Nitrobenzene (1)	2	84	209–211 (ref. 31a)
4-Nitrotoluene (2)	2	83	52–54 (ref. 31a)
2-Nitrophenol (3a)	1	53	44–47 (ref. 32)
4-Nitrophenol (3b)		35	114–116 (ref. 31a)
1-Nitronaphtalene-2-ol (4)	Immediately	92	101–103 (ref. 32)
4-Chloro-2-nitrophenol (5)	2	78	83–85 (ref. 31b)
4-Bromo-2-nitrophenol (6)	Immediately	85	82–84 (ref. 31b)
1-Nitronaphthalene (7)	Immediately	82	58–61 (ref. 8)
9-Nitroanthracene (8)	2	83	137–140 (ref. 33)
2-Nitro4-benzyl phenol (9)	1	81	83–86
2-Nitroaniline (10a)	Immediately	45	71–73 (ref. 34)
4-Nitroaniline (10b)		40	148–151 (ref. 35)
1,2-Diphenyldisulfide (11)	2	83	62–65 (ref. 31a)
1-Bromo 4-nitrobenzene (12)	2	80	122–124
1-(Naphthalen-2-yl)-2-(naphthalen-6-yl)disulfane (13)	2	75	138–141
4-Nitro anisol (14)	1	90	52–54 (ref. 31a)
1-((E)-2-nitrovinyl)benzene (15)	3	62	55–58 (ref. 30)

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Scheme 4 Regioselective nitration of styrene.

In a proposed mechanism which is supported by literature,⁸ NO₂ gas released from [pyridine–SO₃H]NO₃ reacts with aromatic compound to give the aromatic radical and nitrous acid (HNO₂). Second NO₂ radical and the aromatic radical react to yield nitro naphthalene (Scheme 5).

Scheme 5 The proposed mechanism for the nitration of aromatic compounds using [pyridine–SO₃H]NO₃.

To investigate the regeneration of [pyridine–SO₃H]NO₃, the reaction of 2-naphthol with reagent was carried out several times, and the resulting ionic liquid phases (unreacted [pyridine–SO₃H]NO₃, the zwitterionic salt, and pyridinium salt) were combined. Water was added to the reaction mixture, and the reaction mixture was stirred for 5 min and then filtered. [Pyridine–SO₃H]NO₃ and zwitterionic salt is soluble in water and separated from the remained starting material and the product. [Pyridine–SO₃H]NO₃ and the zwitterionic salt were hydrolyzed in aqueous media. A solution of NaOH (10%) was then added to the reaction media, and the mixture was stirred for 5 min to give pyridine. The solution was extracted with ethyl acetate, washed with water, and dried. By the evaporation of the solvent, pyridine was separated (96% recovery). The recovered pyridine was reacted with chlorosulfonic acid to afford [pyridine–SO₃H]NO₃. Then, [pyridine–SO₃H]NO₃ reacted with nitric acid (100%) to prepare [pyridine–SO₃H]NO₃. The activity of the reproduced [pyridine–SO₃H]NO₃ as nitration agent was almost identical to the original version (Scheme 6).

Scheme 6 Regeneration of [pyridine–SO₃H]NO₃.

To compare the efficiency of the solution versus solvent-free conditions, a mixture of 2-naphthol (1 mmol) and [pyridine–SO₃H]NO₃ (1 mmol) in some various solvents was investigated at room temperature. In the presence of several various solvents such as CH₂Cl₂, CHCl₃, EtOAc, EtOH and H₂O, the product was obtained in low yields (Table 2).

Table 2 Effect of various solvents on the reaction of 2-naphthol (1 mmol) with {[pyridine–SO₃H]NO₃} (1 mmol) at room temperature

Solvent	Time (min)	Yield^a (%)
a Yield of purified product.
EtOAC	60	65
CHCl3	60	60
CH2Cl2	10	92
EtOH	60	25
H2O	60	15

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To confirm the existence of NO₂ radical in the reaction media, we studied the effective application of NO₂ with iodine or butylated hydroxytoluene (BHT) as a radical scavenger on a model reaction with naphthalene (Scheme 7).³⁶ In the presence of iodine; the yield of 1-nitro naphthalene was very low even after 24 hours. Nitration of naphthalene was also tested using butylated hydroxytoluene (BHT) as a radical scavenger. In this reaction condition, nitration process was carried out slowly and the yield of 1-nitronaphthalene was decreased even after long reaction time due to major suppression of the active species in this reaction condition (Table 3).

Scheme 7 Trapping NO₂ radical with iodine and butylated hydroxytoluene (BHT).

Table 3 Effect of iodine and butylated hydroxytoluene as radical scavengers on the nitration of naphthalene (1 mmol) in the presence of {[pyridine–SO₃H]NO₃} (1 mmol)

Entry	Radical scavenger (mmol)	Time (min)	Yield^a (%)
a Yield of purified product.
1	—	Immediately	92
2	I2 (0.3)	1440	35
3	I2 (0.7)	1440	20
4	I2 (1)	1440	10
5	BHT (0.3)	1440	45
6	BHT (0.7)	1440	35
7	BHT (1)	1440	20

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To compare the efficiency of [pyridine–SO₃H]NO₃ with the reported nitrating methods nitration of toluene was chosed. As Table 4 indicates that, [pyridine–SO₃H]NO₃ has remarkably improved result compared with other methods shown in Table 4.

Table 4 Comparison of the results on the nitration of toluene using [pyridine–SO₃H]NO₃ with those obtained by the recently reported methods

Reaction condition	Time (min)	Yield^a (%)	Ref.
a Isolated yield.b Our work.
PVP–HNO3 and PVP–H2SO4 CH2Cl2, r.t.	120	55	37
Bi(NO3)3·5H2O (1.5 equv.) bmim (PF6), 85 °C	90	39	38
Bi(NO3)3·5H2O (1.5 equv.) 1,2-DCE, 85 °C	1380	50	38
[Msim] NO3, CH2Cl2, r.t.	2	70	8
VO(NO3)3, CH2Cl2, r.t.	6	41	39
Toluene (1 mmol), NaNO2 (1 mmol), CF3CO2H (34 mmol), r.t.	240	48	40
[Py–SO3H]NO3, solvent-free, r.t.	2	83	–^b

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1. Conclusions

Herein, we designed and synthesized the ionic liquid 1-sulfopyridinium nitrate [pyridine–SO₃H]NO₃ as a new, a highly efficient and organic reagent without the need of a co-catalyst and solvent for the nitration of various aromatic compounds at room temperature.

2. Experimental

2.1. General

All chemicals were purchased from Merck or Fluka Chemical Companies. The known products were identified by comparison of their melting points and spectral data with those reported in the literature. Progress of the reactions was monitored by TLC using silica gel SIL G/UV 254 plates.

The ¹H NMR (400 or 300 MHz) and ¹³C NMR (100 or 75 MHz) were recorded on a Bruker Avance DPX FT-NMR spectrometer (δ in ppm). Melting points were recorded on a Büchi B-545 apparatus in open capillary tubes. Thermogravimetric (TG) and differential thermal gravimetric (DTG) were analyzed by a Perkin Elmer (model: Pyris 1). TG/DTG analysis (0 to 600 °C, temperature increase rate of 10 °C min⁻¹, nitrogen atmosphere).

2.2. General procedure for the preparation of the ionic liquid [pyridine–SO₃H]NO₃

A solution of pyridine (0.395 g, 5 mmol) in CH₂Cl₂ (40 mL) was added dropwise to a stirring solution of chlorosulfonic acid (0.58 g, 5 mmol) in dry CH₂Cl₂ (40 mL) over a period of 10 min at 0 °C. After the addition was completed, the reaction mixture was stirred for 20 min, stood and for 5 min, and the CH₂Cl₂ was decanted. Afterwards the liquid residue was triturated with CH₂Cl₂ (3 × 10 mL), and dried under powerful vacuum at 90 °C to give [pyridine–SO₃H]Cl as a viscous colorless oil in 95% yield (0.929 g).^24,25 Then, nitric acid 100% (0.315 g, 5 mmol) was dropwise added to [PySO₃H]Cl (0.993 g, 5 mmol) over a period of 5 min at room temperature under a continuous flow of nitrogen to remove the HCl gas that is produced. The resulting mixture was stirred for 10 min under these conditions to give [pyridine–SO₃H]NO₃ as a viscous yellow red oil in 97% yield.

1-Sulfopyridinium nitrate. Yellow Red oil; IR (Nujol) cm⁻¹; 1183, 1308, 1543, 3100–3600; ¹H NMR (300 MHz, DMSO-d₆) δ (ppm) 8.11–8.14 (t, J = 9 Hz, 2H), 8.64–8.69 (m, 1H), 8.95–8.97 (d, J = 6 Hz, 2H), 11.37 (s, 1H); ¹³C NMR (75 MHz, DMSO-d₆) δ (ppm) 127.85, 142.17, 147.23. Anal. calcd (%) for C₅H₆N₂O₆: C, 25.03; H, 3.36; N, 11.66; S, 13.35. Found: C, 24.22; H, 3.115; N, 11.95; S, 13.51.

2.3. General procedure for the nitration of compounds

To a round-bottomed flask (10 mL) was added [pyridine–SO₃H]NO₃ (0.222 g, 1 mmol). The aromatic compound (1 mmol) was then added, and the mixture was stirred at room temperature. After the reaction was completed (monitored with TLC), dichloromethane (5 mL) was added to the reaction mixture, and the mixture was stirred for 2 min and separated. The organic solvent was evaporated, and the product was easily purified by short column chromatography. Note: for the nitration of aniline, after the reaction was completed, the reaction mixture was basified to pH 8 by the slow addition of 10% NaOH solution. The organic layer was separated, and the aqueous layer was extracted with dichloromethane. The combined organic solution was washed with brine, dried over MgSO₄, filtered, and concentrated to give a crude product, which was purified with short column chromatography.

Acknowledgements

We thank Bu-Ali Sina University and Iran National Science Foundation (INSF) (The Grant of Allameh Tabataba'i's Award, Grant Number BN093) and Sayyed Jamaleddin Asadabadi University for providing support to this work.

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra15922b

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