The Journal of Organic Chemistry
NOTE
a six-membered structure (ii), and enable elimination of ammonia
rather than an amide anion (iii). The six-membered hydrogen-
3-Hydroxy-4-nitroaniline (2e). 1H NMR (400 MHz, DMSO-d6)
δppm 6.11 (dd, J = 8, 2 Hz, 1H), 6.27 (d, J = 2 Hz, 1H), 7.38 (br s, 2H),
7.86 (d, J = 8 Hz, 1H), 10.62 (br s, 1H); 13C NMR (100 MHz,
DMSO-d6) δppm 100.8, 107.1, 124.5, 128.0, 148.8, 164.0; ESI-MS
m/z 153 [(M ꢀ H)ꢀ].
bonded Meisenheimer complex eq-7aꢀ H2O are suggested by
ꢀ3 3 3
DFT calculations for a set of 2a, OH , and H2O.18 The results
contrast with those emanating from studies of conventional SNAr
chemistry that show the nitroanilines have low SNAr reactivities in
organic solvents. This rule is generally applicable for various
nitroanilines. As a result, the present findings add a new insight
into the long history of the SNAr chemistry.
3-Chloro-4-nitrophenol (4d). 1H NMR (400 MHz, DMSO-d6)
δppm 7.05 (dd, J = 8, 2 Hz, 1H), 7.18 (d, J = 2 Hz, 1H), 7.94 (d, J = 8 Hz,
1H), 11.50 (br s, 1H); 13C NMR (100 MHz, DMSO-d6) δppm 118.5,
119.3, 127.0, 135.9, 139.0, 152.9; ESI-MS m/z 173 [(M ꢀ H)ꢀ].
2-Hydroxy-4-nitrophenol (4-Nitrocatechol, 4f). 1H NMR
(400 MHz, DMSO-d6) δppm 6.93 (d, J = 8 Hz, 1H), 7.64 (s, 1H),
7.67 (d, J = 8 Hz, 1H), 10.30 (br s, 2H); 13C NMR (100 MHz, DMSO-
d6) δppm 110.5, 115.0, 116.5, 139.6, 145.5, 152.9; EI-MS m/z 155 (M+).
2-Methyl-4-nitrophenol (4-Nitro-2-cresol, 4g). Mp 96ꢀ
’ EXPERIMENTAL SECTION
General Methods. 1H and 13C NMR spectra were recorded at 400
and 100 MHz, respectively. All melting points were measured on a
melting point apparatus and are reported uncorrected.
1
97 °C (lit. 93ꢀ98 °C23); H NMR (400 MHz, CDCl3) δppm 2.32
(s, 3H), 5.87 (s, 1H), 6.87 (d, J = 9 Hz, 1H), 8.01 (dd, J = 9, 3 Hz, 1H),
8.07 (d, J = 3 Hz, 1H); 13C NMR (100 MHz, CDCl3) δppm 15.8,
114.9, 123.7, 125.2, 126.9, 141.3, 159.7; EI-MS m/z 153 (M+).
2-Methoxy-4-nitrophenol (4h). Mp 103ꢀ104 °C (lit. 103ꢀ
Typical Procedure for SNAr Reactions of Nitroanilines in
Aqueous NaOH. A mixture of 4-nitroaniline (2a, 4.4 g, 32 mmol) and
1.5 M aqueous NaOH (110 mL, containing 165 mmol of NaOH) was
stirred for 4 h at 100 °C. The smell of ammonia showed progress of the
reaction. The mixture was cooled to room temperature, 200 mL of H2O
was added before extracting twice with EtOAc, and the combined
organic layers were washed with dilute aqueous NaOH and H2O, dried
over Na2SO4, and concentrated in vacuo giving 2.7 g of yellow solid of
recovered 2a (60%). The aqueous alkali layer obtained from the
extractions was neutralized by addition of 17 g of acetic acid and the
resulting solution was extracted twice with EtOAc. The combined
extracts were washed with brine, dried over Na2SO4, and concentrated
in vacuo giving 1.7 g of yellowish solid of 4-nitrophenol (4a) (40%).
Typical Procedure of SNAr Reaction of 2,4-Dinitroanilines
in Aqueous nBu4NOH (Table 2, entries 1 and 2). A solution of
1
104 °C20); H NMR (400 MHz, CDCl3) δppm 4.00 (s, 3H), 6.21 (s,
1H), 6.99 (d, J = 9 Hz, 1H), 7.77 (d, J = 2 Hz, 1H), 7.89 (dd, J = 9, 2 Hz,
1H); 13C NMR (100 MHz, CDCl3) δppm 56.4, 106.3, 113.9, 118.6,
141.2, 146.1, 151.6; EI-MS m/z 169 (M+).
2-Amino-4-nitrophenol (4i). Mp 141ꢀ142 °C (lit. 140ꢀ
1
143 °C23); H NMR (400 MHz, DMSO-d6) δppm 5.17 (br s, 2H),
6.75 (d, J = 9 Hz, 1H), 7.37 (dd, J = 9, 3 Hz, 1H), 7.44 (d, J = 3 Hz,
1H), 10.53 (br s, 1H); 13C NMR (100 MHz, DMSO-d6) δppm 107.7,
113.0, 113.1, 137.6, 140.2, 150.6; EI-MS m/z 154 (M+).
2-Nitrophenol (9j). 1H NMR (400 MHz, CDCl3) δppm 7.00 (t, J =
8 Hz, 1H), 7.16 (d, J = 8 Hz, 1H), 7.58 (t, J = 8 Hz, 1H), 8.10 (d, J = 8 Hz,
1H), 10.57 (br s, 2H); 13C NMR (100 MHz, CDCl3) δppm 120.0, 120.2,
125.1, 133.8, 137.6, 155.2; EI-MS m/z 139 (M+).
n
sulfolane (65 mL), 40 wt % (1.5 M) aqueous Bu4NOH (112 mL,
containing 168 mmol of nBu4NOH), and toluene (60 mL) was distilled
under atmospheric pressure to remove 66 mL of H2O and 60 mL of
toluene before the addition of 1b or 2b (32 mmol). The resulting solutions
were stirred for 16 h at100°C and then subjected to the workup procedure
described above.
4-Methoxy-2-nitrophenol (9k). Mp 79ꢀ80 °C (lit. 78ꢀ
1
80 °C23); H NMR (400 MHz, CDCl3) δppm 3.83 (s, 3H), 7.09
(d, J = 9 Hz, 1H), 7.22 (dd, J = 9, 3 Hz, 1H), 7.51 (d, J = 3 Hz, 1H),
10.33 (s, 1H); 13C NMR (100 MHz, CDCl3) δppm 56.0, 105.7,
120.8, 127.2, 133.0, 150.0, 152.6; EI-MS m/z 169 (M+).
1
4-Nitrophenol (4a). Mp 113ꢀ114 °C (lit. 114 °C19); H NMR
4-Amino-2-nitrophenol (9l). Mp 125ꢀ126 °C (lit. 125ꢀ
1
127 °C23); H NMR (400 MHz, DMSO-d6) δppm 5.10 (br s, 2H),
(400 MHz, DMSO-d6) δppm 6.96 (AA0XX0, J = 8 Hz, 2H), 8.14
(AA0XX0, J = 8 Hz, 2H), 11.10 (br s, 1H).
6.87 (br s, 1H), 6.87 (br s, 1H), 7.09 (br s, 1H), 9.80 (br s, 1H); 13C
NMR (100 MHz, DMSO-d6) δppm 107.0, 119.9, 123.5, 135.6, 141.7,
143.8; EI-MS m/z 154 (M+).
2,4-Dinitrophenol (4b). Mp 112ꢀ113 °C (lit. 108ꢀ112 °C20);
1H NMR (400 MHz, DMSO-d6) δppm 7.35 (d, J = 8 Hz, 1H), 8.48 (dd,
J = 8, 2 Hz, 1H), 9.08 (d, J = 2 Hz, 1H, Ph), 10.97 (br s, 1H); 13C NMR
(100 MHz, DMSO-d6) δppm 121.3, 121.9, 131.7, 132.6, 140.3, 159.1;
ESI-MS m/z 183 [(M ꢀ H)ꢀ].
’ ASSOCIATED CONTENT
1
S
Supporting Information. The DFT calculations for
N,N-Di-n-butyl-2,4-dinitroaniline (5b). H NMR (400 MHz,
b
7aꢀ H2O and for Figure 2 and the complete ref 16. This material
CDCl3) δppm 0.90 (t, 6H, CH3), 1.27 (sex, 4H, CH2), 1.59 (f, 4H, CH2),
3.28 (t, 4H, CH2), 7.07 (d, J = 8 Hz, 1H), 8.19 (dd, J = 8, 2 Hz, 1H), 8.64
(d, J = 2 Hz, 1H); 13C NMR (100 MHz, CDCl3) δppm 13.7, 20.0, 29.4,
52.0, 118.8, 124.0, 127.6, 136.7, 137.6, 148.7; EI-MS m/z 295 (M+).
3 3 3
’ AUTHOR INFORMATION
1
3-Hydroxy-4-nitrochlorobenzene (1e). H NMR (400 MHz,
Corresponding Author
*E-mail: mizuno@chem.osakafu-u.ac.jp; ikeda@chem.osakafu-u.ac.jp.
DMSO-d6) δppm 7.05(dd, J = 8, 2 Hz, 1H), 7.19 (d, J = 2 Hz, 1H), 7.94 (d,
J = 8 Hz, 1H), 11.50 (br s, 1H); 13C NMR (100 MHz, DMSO-d6) δppm
118.6, 119.4, 127.0, 135.9, 139.1, 153.0; ESI-MS m/z 172 [(M ꢀ H)ꢀ].
3-Amino-4-nitrophenol (4c). Mp 183ꢀ184 °C (lit. 185ꢀ
’ ACKNOWLEDGMENT
1
186 °C21); H NMR (400 MHz, DMSO-d6) δppm 6.13 (dd, J = 8,
This study was supported by the Cooperation for Innovative
Technology and Advanced Research in Evolutional Area (CITY
AREA) program by the Ministry of Education, Culture, Sports,
Science and Technology (MEXT), Japan. H.I. gratefully ac-
knowledges financial support in the form of a Grant-in-Aid for
Scientific Research on Priority Areas “New Frontiers in Photo-
chromism” (Nos. 20044027 and 21021025 in the Area No. 471)
and Innovative Areas “π-Space” (Nos. 21108520 and 23108718
2 Hz, 1H), 6.29 (d, J = 2 Hz, 1H, Ph), 7.40 (br s, 2H, NH2), 7.88 (d, J =
8 Hz, 1H), 11.60 (br s, 1H); 13C NMR (100 MHz, DMSO-d6) δppm
100.8, 107.1, 124.6, 128.0, 148.8, 164.0; ESI-MS m/z 153 [(M ꢀ H)ꢀ].
3-Hydroxy-4-nitrophenol (4-Nitroresorcinol, 4e). Mp 121ꢀ
122 °C (lit. 121ꢀ122 °C22); 1H NMR (400 MHz, DMSO-d6) δppm 3.51
(br s, 1H), 6.43 (dd, J = 8, 2 Hz, 1H), 6.46 (d, J = 2 Hz, 1H), 7.92 (d, J = 8
Hz, 1H), 10.88 (br s, 1H); 13C NMR (100 MHz, DMSO-d6) δppm 103.6,
108.8, 127.7, 128.0, 156.0, 165.0; ESI-MS m/z 154 [(M ꢀ H)ꢀ].
6360
dx.doi.org/10.1021/jo2007219 |J. Org. Chem. 2011, 76, 6356–6361