Solid-Phase Aromatic Nitration with Mg ( NO 3 ) 2 on Silica Gel

Nitroaromatics are usually prepared using a mixed acid of nitric acid with strong acids. However, the use of strong acids caused dangerous work-up and the disposal of large amounts of acid-waste. Therefore, much effort has been made on the improvement of nitration process without strong acids. We examined solid-phase aromatic nitration with Mg(NO3)2 on silica gel in order to establish the nitration process without strong acids. The nitration of 1,2and 1,3-, 1,4-dimethoxybenzenes and 4-methylanisole with Mg(NO3)2 proceeded by heating on silica gel at 150 ̊C for 4 5 h to produce the nitroaromatics. The nitration of 1,3,5-trimethoxybenzene produced the nitrated dimer, 2,4,6,2’, 4’,6’-hexamethoxy-3-nitrobiphenyl, which was not isolated in other solid-phase nitration. In the cases of naphthalene derivatives, the α-nitrated compounds were obtained. In the cases of p-cresol and 2-naphthol, the esterification occurred at the hydroxyl group to give 4-tolyl nitrate and 2-naphthyl nitrate, respectively. It is synthetic interest to note that nitrate esters were isolated in solid phase. Thus Mg(NO3)2-SiO2 composite was mild reagent for solid-phase nitration. Acidity of Mg(NO3)2-SiO2 composite was determined to be pH 0.96 by the measurement of absorption spectra on a micro spectrophotometer using meso-tetra(p-cyanophenyl)porphyrin as a pH-indicator. Mg(NO3)2-SiO2 composite made acidic conditions. Therefore, it was suggested that Mg(NO3)2 reacted with proton on silica gel to form the 2 NO + . Thus, electron-rich aromatic hydrocarbons led the efficient nitration through electrophilic attack of 2 NO + . After the nitration, acidic Mg(NO3)2-SiO2 composite could be turned into neutrality by exposing wet conditions and disposed safely since the composite did not involve harmful elements. Thus the solid-phase nitration using Mg(NO3)2-SiO2 composite will provide safety and environmentally conscious chemical process. How to cite this paper: Matsumoto, T., Yamauchi, A., Ishikawa, J., Jin, G.-H., Matsumoto, J., Fueda, Y. and Yasuda, M. (2017) Solid-Phase Aromatic Nitration with Mg(NO3)2 on Silica Gel. International Journal of Organic Chemistry, 7, 1-11. https://doi.org/10.4236/ijoc.2017.71001 Received: September 30, 2016 Accepted: December 24, 2016 Published: December 27, 2016 Copyright © 2017 by authors and Scientific Research Publishing Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0). http://creativecommons.org/licenses/by/4.0/ Open Access


Introduction
Nitroaromatics are important chemicals which are applicable to dyes, explosives, pharmaceuticals, and the intermediates to prepare amines.Industrial synthesis of nitroaromatics has been achieved using a mixed acid of nitric acid with strong acids (e.g.sulfuric acid).However, the use of strong acids caused dangerous work-up and the disposal of large amounts of acid-waste.Therefore, much effort has been made on the improvement of nitration process without strong acids [1].Preliminarily in order to avoid the risk of sulfuric acid, sulfuric acid was supported on silica gel to apply to the aromatic nitration with nitric acid (HNO 3 ) [2].Recently, silica gel which is the most commonly desiccant [3] has been used as a dehydration agent instead of sulfuric acid together with nitration reagents such as Bi(NO 3 ) 3 [4], HNO 3 [5], Ce(NH 4 )(NO 3 ) 5 [6], and AcONO 2 [7] in solid state.Also, montmorillonite and charcoal were used for solid-state aromatic nitration with Bi(NO 3 ) 3 [8] and Zn(NO 3 ) 2 [9].Also, Bi(NO 3 ) 3 [10] and NaNO 2 [11] were used as reagents for indirect nitration in solution phase.Thus solid-phase nitration using nitrate salts such as Bi(NO 3 ) 3 , Al(NO 3 ) 3 •9H 2 O [12] [13] and Zn(NO 3 ) 2 on silica gel has been reported so far.
More than a decade ago, we started to develop cobalt-free humidity indicator for silica gel desiccant using Mg salts and porphyrins [14].In those days, the desiccant ability of silica gel has been checked by color change of the CoCl 2 adsorbed on silica gel (CoCl 2 -SiO 2 , silica gel blue).However, considerable caution had to be paid to the CoCl 2 -SiO 2 because CoCl 2 was determined to be carcinogenic to humans by International Agency for Research on Cancer [15].Therefore, it was required to use the humidity indicators instead of CoCl 2 -SiO 2 .On the other hand, Gordeeva and co-workers have reported that acidic conditions were made by the reaction of SiO 2 with CaCl 2 under dry conditions [16].In order to develop new type of humidity indicator, we mixed MgCl 2 -SiO 2 with pH-sensitive tetraphenylporphyrin and dried under heating to prepare a porphyrin-MgCl 2 -SiO 2 (Indicator F TM , Fuji Silysia), which caused color change from green under dry conditions to pink under wet conditions [17].During the investigations, we measured the pH of the composites of Mg salts (MgCl 2 , MgSO 4 , Mg(NO 3 ) 2 ) with SiO 2 using several kinds of tetraarylporphyrins with different basicity [18].In the case of the combination of Mg(NO 3 ) 2 -SiO 2 and tetra(p-methoxyphenyl) porphyrin, the porphyrin was nitrated.This observation led us to use Mg(NO 3 ) 2 for the solid-phase aromatic nitration since there was no report on the nitration using Mg(NO 3 ) 2 .
Here, we investigated the solid-phase nitration of aromatic hydrocarbons (1) with a composite of Mg(NO 3 ) 2 with silica gel (Mg(NO 3 ) 2 -SiO 2 ) in order to establish the nitration process without strong acids.

Instrument
1 H NMR (400 MHz) and 13 C NMR (100 MHz) spectra were taken with a Bruker AV 400M spectrometer for CDCl 3 solution using SiMe 4 as an internal standard.High-resolution mass spectra (HRMS) were measured on a Thermo Scientific Q Exactive mass spectrometer equipped with an electrospray ionization source.Almost HRMS spectra were measured at positive mode except for the cases of 4f and 4j which were measured in negative mode.Microscopic spectrophotometry was performed on a confocal laser scanning microscope (CLSM; Olympus FV-300, Japan) equipped with a spectrophotometer (STFL 250, Seki Technotron, Japan) linked to the CLSM by an optical fiber.Using a 10 folds magnification lens, the measurable area was restricted to the inside of a circle with a 8.56 μmdiameter [18].Microscopic absorption spectra were taken using a back-light as the light source.

Nitration of Aromatic Hydrocarbons (1) with Mg(NO 3 ) 2 on Silica Gel
General procedure of solid-phase nitration was performed as follows.A MeOH solution (10 mL) containing 1,4-dimethoxybenzene (1a; 3.62 mmol, 500 mg) and Mg(NO 3 ) 2 •6H 2 O (504.9 mg, 1.97 mmol, Wako Chemicals, Japan ) was added slowly to silica gel (2.92 g, 48.7 mmol, Fuji Silysia A type, the average diameter = 79 μm) in a flask.After standing for 30 min to adsorb 1a and Mg(NO 3 ) 2 on silica gel, the solvent was removed by evaporation.The resulting composite of 1a, Mg(NO 3 ) 2 , and silica gel was heated at a given temperature under N 2 atmosphere for 4-10 h under vigorous magnetic steering.The reacted composite was set on a silica gel column (Fuji Silysia BW 300, 50 mL) and was subjected to chromatography.Starting material (1a) and the nitrated products (2a) were isolated by elution with hexane and CHCl 3 , respectively.The products were listed in Scheme 1.The 2a-2c, 2e-2i, 3d, 4f, and 4j had the following spectral data.

Measurement of Acidity of the Mg(NO 3 ) 2 -SiO 2 Composite
According to the reported method [18], the acidity of the Mg(NO 3 ) 2 -SiO 2 composite was measured as follows.At first, absorption spectra of H 2 tcp were measured in CHCl 3 -MeOH (1:2, v/v) under different pHs which were adjusted by HClO 4 .The absorptions were observed at 514 and 645 nm due to purple free base porphyrin (H 2 tcp) and the greenish protonated porphyrin (H 4 tcp 2+ ), respectively.The absorbances (A P and A G ) were measured at 514 nm and 645 nm, respectively.Fraction (F = A P /(A G + A P )) was calculated at every pH and plotted against the pH to make the pH-profile of F values (Figure 1).The pH-profile was fitted by sigmoid curves (Equation ( 1)) which was presented by three parameters, F max , pKa, and S, which denotes maximum F values, acid dissociation constant of H 4 tcp 2+ , and slope of the fitting curve at pKa, respectively.The relative standard deviation (RSD) was 0.9996.Each value of F max , pKa, and S for H 2 tcp were determined to be 0.875, 1.376, and 6.220, respectively.
When the aromatic hydrocarbon was not added the Mg(NO 3 ) 2 -SiO 2 composite, acidity of the Mg(NO 3 ) 2 -SiO 2 composite was measured in a solid state using the pH-profile as follows.A CHCl 3 solution (10 mL) of H 2 tcp (0.7 μmol) and an aqueous solution (2 mL) of Mg(NO 3 ) 2 (173 mg) were mixed with SiO 2 (1.0 g, Fuji silysia A type, 1.8 -5.0 mm).Here, large sizes of silica gel were used for CLSM analysis.After standing for 2 h until almost all of the H 2 tcp had been adsorbed on Mg(NO 3 ) 2 -SiO 2 composite, the solvent was evaporated and the H 2 tcp-Mg(NO 3 ) 2 -SiO 2 composite was dried under reduced pressure.Figure 2 shows the absorption spectra of H 2 tcp adsorbed on a Mg(NO 3 ) 2 -SiO 2 composite which was measured for five beads on CLSM.The F-values were determined to be 0.06 ± 0.04 by averaging five spectra.Using fitting curves, F-values were converted to pH, which was determined to be 0.96 for the Mg(NO 3 ) 2 -SiO 2 composite under dry conditions.
The results are summarized in Table 1.

Reaction Pathways
The silica gel is constructed by Si-O bonds such as Si-O-Si, Si=O, and Si-OH.It is well-known that the Si-OH group remained on the surface under heating below 300˚C [7].We previously elucidated that the Si-OH on silica gel could react with MgCl 2 and MgSO 4 under dry conditions to release proton [18].Their acidities were determined by the colorimeter analysis using meso-tetraarylporphyrin as a pH-indicator.In the present study, the reaction of Mg(NO 3 ) 2 with silica gel generated HNO 3 along with the adsorption of Mg 2+ ion on silica gel (Equation ( 2)).The acidity (pH) of Mg(NO 3 ) 2 -SiO 2 composite was determined to be 0.96, which was more acidic compared with MgCl 2 -SiO 2 and MgSO 4 -SiO 2 composites whose pH were 1.73 and 1.61, respectively.The presence of excess water made the pH of Mg(NO 3 ) 2 -SiO 2 neutral.Aromatic nitration usually occurs under acidic conditions.It was suggested that HNO 3 reacted with the proton to form the 2 NO + (Equation ( 3)).More electron-rich aromatic hydrocarbons (1a and 1d) were allowed the efficient nitration.Therefore, the nitration proceeded through electrophilic attack of 2 NO + to the aromatic ring (Equation ( 4)).Mg(NO 3 ) 2 and silica gel played as nitration reagent and desiccant, respectively.

Generation of H
In order to elucidate the mechanism of the formation of 3d, acid-catalyzed dimerization of 1d was attempted by the heating of 1d on silica gel at 150˚C for 7 h with MgCl 2 which can release proton but has no electrophilicity.The dimerization of 1d did not occur.It is well known that the dimerization of aromatic hydrocarbons in the presence of electrophiles has been reported [28].The electrophilic attack of NO 2 + to 1d gave intermediates 5A and/or 5B.The 5A is less stable and more reactive than 5B, leading to the reaction of 5Awith another 1d at ortho and/or para positions (Friedel-Crafts acylation) to give the dimer which allowed the nitration to form 3d (Scheme 2).

Conclusion
In conclusion, the solid phase nitration of electron-rich aromatic hydrocarbons such as 1,4-dimethoxybenzene (1a) proceeded using Mg(NO 3 ) 2 on silica gel.Unique nitration occurred in 1,3,5-trimethoxybenzene (1d) which afforded nitrated dimer.In the cases of p-cresol (1f) and 2-naphthol (1j), esterification occurred to give aromatic nitrates.Thus the combination of Mg(NO 3 ) 2 with silica gel can eliminate the use of sulfuric acid from the aromatic nitration.Moreover, the acidic Mg(NO 3 ) 2 -SiO 2 composite could be turned into neutrality by only exposing wet conditions and disposed safely since the composite did not involve harmful elements.Thus the solid-phase nitration using Mg(NO 3 ) 2 -SiO 2 composite will provide safety and environmentally conscious chemical process.

Figure 1 .
Figure 1.The pH-dependence of F values of H2tcp in CHCl3-MeOH.The pH was adjusted by HClO4.

Figure 2 .
Figure 2. Measurement of absorption spectra of five beads of the H2tcp-adsorbed Mg(NO3)2-SiO2 under dry conditions using CLSM.