Bromodimethylsulfonium bromide/tetrabutylammonium nitrite: An efficient catalyst mixture for the nitration of phenols

Article abstract of DOI:10.3906/kim-0909-246

Nitrophenols were obtained via direct nitration of phenols with tetrabutylammonium nitrite in the presence of bromodimethylsulfonium bromide at room temperature in high yields under aprotic conditions. TUeBITAK.

Full text of DOI:10.3906/kim-0909-246

Turk J Chem
34 (2010) , 753 – 759.
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˙
c
ꢀ TUBITAK
doi:10.3906/kim-0909-246
Bromodimethylsulfonium bromide/tetrabutylammonium
nitrite: an efficient catalyst mixture for the nitration of
phenols
Batool AKHLAGHINIA1,∗, Alireza POURALI2
1Department of Chemistry, Faculty of Sciences, Ferdowsi University of Mashhad,
Mashhad-IRAN
2School of Chemistry, Damghan University of Basic Sciences, Damghan-IRAN
e-mail: akhlaghinia@um.ac.ir
Received 19.09.2009
Nitrophenols were obtained via direct nitration of phenols with tetrabutylammonium nitrite in the
presence of bromodimethylsulfonium bromide at room temperature in high yields under aprotic conditions.
Key Words: Bromodimethylsulfonium bromide, nitration, nitrophenol, tetrabutylammonium nitrite
Introduction
The nitration of aromatic compounds is an important industrial process and nitro aromatic compounds so
produced are widely utilized for the synthesis of dyes, pharmaceuticals, perfumes, and plastics.1 Therefore, the
nitration of aromatic rings has received considerable attention of late, due to unsolved problems pertaining to
regioselectivity, polynitration, and competitive oxidation of substrates.2,3 Nitration of the phenol as a special
case has been studied by various nitrating agents under different conditions.1−26 Among the methods that have
been reported in the literature for the regioselective nitration of phenols, 3 procedures yield excellent results.
Two of them used microemulsion and a surface mediated system.21 In the third one, an enzymatic method
was reported for the nitration of phenols.22 Zolfigol and co-workers have reported the use of some hydrated
metal nitrates and their dinitrogen tetroxide complex analogues, as well as ionic metal nitrates or nitrites in
the presence of inorganic acidic salts, for the nitration of phenols under various conditions.23 They have also
reported the application of trichloroisocyanuric acid/NaNO2 /wet SiO2 for mononitration of phenols.26
∗Corresponding author
753

Bromodimethylsulfonium bromide/tetrabutylammonium nitrite: an..., B. AKHLAGHINIA, A. POURALI
To overcome the limitations and drawbacks of the classic methods such as strongly acidic media,15b
tedious work-up,16,17 oxidation and polynitration, and safety problems (storage, handling, using, and also
presence of toxic transition metal cations such as Cr+3 , Hg+2 , and Cu+2 within molecular structure of
the reagents),24,25 and to develop a high-yielding one-pot synthesis of nitrophenols, in this research a novel
combination of bromodimethylsulfonium bromide (BDMS) and tetrabutylammonium nitrite is introduced.
In recent years, the use of BDMS has gained more attention in synthetic organic chemistry. 27 This reagent
is a readily accessible, conveniently stored, less hazardous, easy to handle crystalline solid. So far, BDMS
has been utilized for the transformation of alcohols to the corresponding bromides,28a oxidation of thiols to
disulfides,28b deprotection of dithioacetals,28c preparation of α-bromoenones from the corresponding enones,28d
electrophilic aromatic bromination,28e regioselective α-bromination of β-keto esters and 1,3-diketones,28b and
thiocyanation of aromatic compounds.28f Herein, we report a novel, mild, and efficient approach for the nitration
of aromatic compounds using BDMS in the presence of tetrabutylammonium nitrite (Scheme 1).
OH
OH
NO2
(CH3)2SBr2
/
n-Bu4NNO2
CH3CN , room temperature
R
2
R
1
R
1A, 2A: CH3
R
1G, 2G: F
1B, 2B: CH2Ph
1C, 2C: OCH3
1H, 2H: CHO
1I, 2I: COOH
1J, 2J: CN
1D, 2D: Ph
1E, 2E: Br
1F, 2F: Cl
1K, 2K: NO2
Scheme 1
Experimental
The products were purified by column chromatography and the purity determinations of the products were
accomplished by GLC on a Shimadzu model GC-10A instrument or by TLC on silica-gel polygram STL G/UV
254 plates. FT-IR spectra were recorded on a Shimadzu–IR 470 spectrometer. NMR spectra were recorded on
a Bruker AC 300 MHz instrument. Elemental analyses were performed using a Thermofinnigan Flash EA 1112
Series instrument.
754

Bromodimethylsulfonium bromide/tetrabutylammonium nitrite: an..., B. AKHLAGHINIA, A. POURALI
All products were identified by their comparison with authentic samples. Bromodimethylsulfonium
bromide was prepared and purified by the method described in the literature.28f
General Procedure for Nitration of Substituted Phenols with Bromodimethylsul-
fonium Bromide/n-Bu4 NNO2
To a yellow suspension of bromodimethylsulfonium bromide (0.332 g, 1.5 mmol) and tetrabutylammonium
nitrite (0.864 g, 3 mmol) in anhydrous CH3 CN (10 mL) was added the substrate (1 mmol) in one portion. The
reaction mixture was stirred at r.t. until complete consumption of the starting material as observed by TLC.
After completion of the reaction, it was quenched with saturated solution of NaHCO3 (10 mL) and the solid
residue was removed by filtration and the residue was washed with EtOAc. The organic layer was separated,
washed with H2 O (10 mL) and brine (10 mL), dried over anhydrous Na2 SO4 , and concentrated under reduced
pressure to give the crude nitro product. Pure product was obtained after column chromatography using
n-hexane/ethylacetate (3/2 v/v) as eluent.
Results and discussion
To begin our study, the effect of various reaction conditions on the nitration of p-cresol was examined.
The reaction was carried out with different molar ratios of p-cresol, bromodimethylsulfonium bromide and
tetrabutylammonium nitrite. The optimized stoichiometric molar ratios of p-cresol/BDMS/n-Bu4 NNO2 were
found to be 1/1.5/3 and the best results (1 h, 100% conversion) were obtained when the reaction was performed
in CH3 CN at room temperature (Table, entry A).
Different kinds of 4-substituted phenols were also subjected to nitration in the presence of BDMS /n-
Bu4 NNO2 in acetonitrile (Scheme 1). The nitration reactions were performed under mild and non-acidic
conditions at room temperature with excellent conversion and high isolated yields (Table). The present nitration
reactions can be readily carried out by placing the nitrating agents, phenols, and the solvent in a reaction vessel
and efficiently stirring the resultant mixture at room temperature. Highly pure mono nitrophenols can be
obtained.
All the substrates, even those with electron-withdrawing substituents, exhibit high reactivity toward
nitration and the corresponding mononitrated phenols were produced in good to excellent yields.
These results indicate that bromodimethylsulfonium bromide is a more superior reagent for electrophilic
aromatic nitration than the previous reported methods. Its high reactivity makes it the reagent of choice for
the nitration of a variety of arenes.
In fact, the mixture of bromodimethylsulfonium bromide and tetrabutylammonium nitrite could promote
the electrophilic reaction via oxidation of nitrite ion (Scheme 2). The mechanism in Scheme 2 suggests that
an initial interaction within bromodimethylsulfonium bromide and tetrabutylammonium nitrite causes the
oxidation of nitrite ion, which generates 1. Then, upon electrophilic attack of 3 as a source of NO+2 , nitrated
phenols are produced followed by elimination of HBr molecule and (CH3)2 S. Nevertheless, at this time there is
no experimental evidence for this feature of 3, and the actual role of this reagent should be further studied in
detail.
755

Bromodimethylsulfonium bromide/tetrabutylammonium nitrite: an..., B. AKHLAGHINIA, A. POURALI
Table. Nitration of substituted phenols using bromodimethylsulfonium bromide/n-Bu4 NNO2 in CH3 CN at room
temperature.
Entry
A
Substrate
1
Producta
2
Time(h)
1
Conversion % b
Isolated
Yield %
(substrate consumption)
1A
1B
2A
2B
OH
OH
NO2
100
100
96
98
CH3
OH
CH3
OH
NO2
NO2
B
70(min)
75(min)
CH2Ph
OH
CH2Ph
OH
1C
2C
C
D
E
100
95
96
OCH3
OH
OCH3
OH
2D
2E
1D
1E
NO2
NO2
NO2
1.5
100
100
Ph
Ph
OH
OH
75(min)
98
88
Br
Br
1F
2F
OH
OH
F
90(min)
1.5
100
100
Cl
Cl
1G
2G
OH
OH
NO2
G
90
F
F
756

Bromodimethylsulfonium bromide/tetrabutylammonium nitrite: an..., B. AKHLAGHINIA, A. POURALI
Table. Continued.
Entry
H
Substrate
1
Producta
2
Time(h)
2
Conversion % b
Isolated
Yield %
(substrate consumption)
1H
2H
OH
OH
100
100
NO2
95
CHO
OH
CHO
OH
2I
1I
NO2
I
93
96
2
COOH
OH
COOH
OH
1J
1K
2J
NO2
J
2.5
100
100
CN
OH
CN
OH
2K
NO2
K
24
97
NO2
NO2
a The products was identified by the comparison of its physical constants and IR and NMR spectral data with those
of an authentic sample. 2A: Mp 28-30 ◦ C, Lit17,29 : 31 ◦ C, 2B: Mp 60-64 ◦ C, Lit23d : 61-66 ◦ C, 2C: Mp 53-55 ◦ C,
Lit23d : 54-56 ◦ C, 2D: Mp 63-65 ◦ C, Lit30 : 66 ◦ C. 2E Mp 81-83 ◦ C, Lit17,29 : 84 ◦ C, 2F: 1 H-NMR (CDCl3): δ 7.13
(d ,1 H, J= 9.27 Hz), 7.53 (dd ,1 H, J=9.1, 2.4 Hz) 8.09 (d, 1 H, J=2.4 Hz), 10.46 (1 H) Mp 88-90 ◦ C, Lit17,29 : 91 ◦ C,
2G: Mp 71-74 ◦ C, Lit15c : 73-74 ◦ C, 2H:1 H-NMR (CDCl3): δ 7.29 (d, 1 H, J=9 Hz), 8.4 (dd, 1H, J= 8.58, 2.07 Hz),
8.62 (d, 1 H, J= 2 Hz), 9.92 (1H ), 10.9 (1 H, CHO). Mp 138-142 ◦ C, Lit15c : 140-142 ◦ C, 2I: Mp 179-182 ◦ C, Lit23d
:
180-184 ◦ C, 2J: Mp 141-143 ◦ C, Lit 15c,29 : 145 ◦ C, 2K: 1 H-NMR (CDCl3): δ 7.32 (d, 1 H, J= 9.0 Hz), 8.44 (dd,
1H, J= 9.27, 2.76 Hz), 9.4 (d, 1 H, J=2.76 Hz), 10.99 (1 H). Elemental analysis data: C%: 38.49 (calc. 39.13), H%: 2.14
(calc.: 2.17), N%: 16.05 (calc.: 15.22).
b GC yield using internal standard (Decalin).
757

Bromodimethylsulfonium bromide/tetrabutylammonium nitrite: an..., B. AKHLAGHINIA, A. POURALI
+ Br
+
Br-
Br-
+
n-Bu4NNO2
(CH3)2S
(CH3)2SNO2
+
n-Bu4NBr
3
OH
OH
NO2
+NO
(CH3)2S
2 Br-
+
(CH3)2S
HBr
+
+
3
R
R
Scheme 2
To conclude, in this research, we have developed a novel method for aromatic nitration of phenols using
a combination of bromodimethylsulfonium bromide and tetrabutylammonium nitrite under aprotic conditions.
The method is a regioselective, efficient, and mild mononitration of phenols with good to excellent yields and
short reaction times.
Acknowledgements
We gratefully acknowledge the partial support of this study by Ferdowsi University of Mashhad Research Council
(Grant no. P/27).
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