Oppi briefs practical and efficient synthesis of 4,4'-dihydroxy-3,3'- dinitrodiphenyl ether and 1,3-bis(4-hydroxy-3-nitrophenoxy)benzene in aqueous alkaline medium

Full text of DOI:10.1080/00304941003689419

Organic Preparations and Procedures International, 42:161–167, 2010
Copyright © Taylor & Francis Group, LLC
ISSN: 0030-4948 print
DOI: 10.1080/00304941003689419
OPPI BRIEFS
Practical and Efficient Synthesis
of 4,4ꢀ-Dihydroxy-3,3ꢀ-dinitrodiphenyl Ether
and 1,3-bis(4-Hydroxy-3-nitrophenoxy)benzene
in Aqueous Alkaline Medium
Mitsutaka Imoto,1,2 Motonori Takeda,2 Akihiro Tamaki,2
Hisaji Taniguchi,1 and Kazuhiko Mizuno1
1Department of Applied Chemistry, Graduate School of Engineering,
Osaka Prefecture University Naka-ku, Sakai, Osaka, Japan
2Wakayama Seika Kogyo Co. Ltd. Wakayama, Japan
4,4ꢀ-Dihydroxy-3,3ꢀ-dinitrodiphenyl ether (4) and 1,3-bis(4-hydroxy-3-nitrophenoxy)
benzene (9) are valuable precursors of 3,3ꢀ-diamino-4,4ꢀ-dihydroxydiphenyl ether1 (5)
and 1,3-bis(3-amino-4-hydroxyphenoxy)benzene2 (10) respectively. The latter two com-
pounds are interesting because of their amphoteric properties in acid-base behavior3 and
as precursors of symmetrical bisphenolic Mannich derivatives of biological interest.4 Fur-
thermore, they are also important starting materials for thermally stable plastics such as
polyamides, polyarylates, polyimides and polybenzoxazoles, which are especially useful as
positive-working photosensitive polymer precursor compositions to form electric interlayer
insulators and protective films for semiconductors.5–11
The critical problem is the synthesis of 4 and 9 as precursors of 5 and 10. So far,
their synthesis has involved the nitration of 4,4ꢀ-dihydroxydiphenyl ether4,7 and 1,3-bis(4-
hydroxyphenoxy)benzene.2 However, the preparation of these compounds12–33 suffers from
very serious problems such as low yields due to low conversion, formation of many unde-
sired by-products, the use of high reaction temperatures and of environmentally harmful
reagents.
In contrast, 4,4ꢀ-diaminodiphenyl ether (1) and 1,3-bis(4-aminophenoxy)benzene
(6) are commercially available and can be selectively nitrated, providing 4,4ꢀ-
diamino-3,3ꢀ-dinitrodiphenyl ether (3) and 1,3-bis(4-amino-3-nitrophenoxy)benzene (8)
quantitatively.34,35 Although compound 4 could be obtained by decomposition of the
Submitted May 22, 2009.
Address correspondence to Mitsutaka Imoto, Department of Applied Chemistry, Graduate School
of Engineering, Osaka Prefecture University, 1-1 Gakuen-choNaka-ku, Sakai, Osaka 599-8531, Japan.
E-mail: m-imoto@waseika.com.
161

162
Imoto et al.
O2N
HO
O
NO2
OH
H2N
HO
O
NH2
OH
NH2NH2 H2O
Pd/C, MeOH, 60 oC
4
5
H2N
O
O
NH2
OH
O2N
HO
O
O
NO2
NH2NH2 H2O
Pd/C, MeOH, 60 oC
HO
OH
9
10
Scheme 1
diazonium salt derived from 3 via the Sandmeyer reaction, the yield was very low due
to many undesired by-products which required complicated purification.
So far, there has been no study on reactions to convert dianilines directly into corre-
sponding diphenols. Although the amino group is generally considered a much poorer leav-
ing group than halide ions in aromatic nucleophilic substitution reactions, there are examples
of replacement of aromatic amino groups activated by one or more nitro groups in aque-
ous alkaline solutions or aqueous organic solvents, providing corresponding phenols,36–42
naphthols43 and quinolinols.44 However, most applications of the reaction are limited to
very activated substrates such as derivatives of 2,4,6-trinitroaniline, 2,4-dinitroaniline.
Thus, the investigations of the reactions of 3 and 8 with hydroxide ion have been
neglected for a long time. It was thought, however, that amino groups of 3 and 8, which have
only one nitro group ortho to the amino group, might become good leaving groups, if the
amino groups are protonated and turned into ArNH3+ in water. From these considerations,
the direct conversion of the amino groups might prove to be a practical synthetic methods
of 4 and 9. This consideration prompted us to investigate the direct conversion of 3, 8 and
of their acetylated derivatives (2 and 7) into 4 and 9 in aqueous alkaline media.
O2N
O
NO2
O
1. Ac2O/AcOH
2. Fuming HNO3
AcNH
NHAc
H2N
NH2
2
1
O2N
H2N
O
NO2
NaOH
100 oC
NaOH
150 oC
4
NH2
3
Scheme 2
Commercially available 1 and 6 were used without further purification. 4,4ꢀ-
bis(N-Acetylamino)-3,3ꢀ-dinitrodiphenyl ether (2) was obtained form 1 in excellent
yield. The deacetylation of 2 provided 3 quantitatively. 1,3-bis(4-N-Acetylamino-3-
nitrophenoxy)benzene (7) was obtained in the same manner.

4,4ꢀ-Dihydroxy-3,3ꢀ-dinitrodiphenyl Ether
163
1. Ac2O/AcOH
2. Fuming HNO3
O2N
O
O
NO2
O
O
AcNH
NHAc
H2N
NH2
6
7
O2N
H2N
O
O
NO2
NH2
NaOH
150 oC
NaOH
100 oC
9
8
Scheme 3
The substitution of 3 in aqueous alkaline media was examined and the results are sum-
marized in Table 1. The reaction was very slow at 100◦C (Entries 1 and 2), but was very
rapid at 150◦C (Entry 3) and provided 4 in an excellent yield after neutralization. Higher
concentration of sodium hydroxide (Entry 4) or addition of tetrabutylammonium chloride
(Entry 5) accelerated the reaction only slightly. Use of tetrabutylammonium hydroxide
in place of sodium hydroxide at 100◦C (Entry 6) showed somewhat more acceleration
albeit the yield of 4 was only 23% due to the high solubility of 9 in 1.5 M aqueous tetra-
butylammonium hydroxide solution. However, cumbersome purification processes were
required to remove a large amount of tar generated through the decomposition of qua-
ternary ammonium ions with hydroxide ions (Hoffmann elimination). Under these condi-
tions, the main product was 4-amino-4ꢀ-hydroxy-3,3ꢀ-dinitrodiphenyl ether (11) formed in
50% yield.
The reaction of 2 and 7 in aqueous sodium hydroxide was examined at 150◦C in
an autoclave and the results are shown in Table 2. Even when the acetylated deriva-
tive 2 was used, the deacetylation and the hydroxylation proceeded simultaneously to give 4
Table 1
Hydrolysis of 3 into 4 in 1.5 M Aqueous Sodium Hydroxide
Temp.
(◦C)
Time
(h)
Recovery of
Yield of
4 (%)
Yield of
11 (%)
Entry
3 (%)
1
2
3
4b
5c
6d
100
100
150a
100
100
100
1
10
1
1
1
100
93
0
91
90
21
0
2
97
2
2
23
0
0
0
5
6
1
50
aCarried out in an autoclave. b6.0 M Sodium hydroxide was used. cTetrabutylammonium chloride
(10 mol %) was added. d1.5 M Aqueous tetrabutylammonium hydroxide was used instead of sodium
hydroxide.

164
Imoto et al.
Table 2
Hydrolysis in 1.5 M Aqueous NaOH at 150 ◦Ca
Entry
Substrate
Product
Time (h)
Yield (%)
1
2b
2
7
4
9
1
5
98
100
aCarried out in an autoclave. b3.0 M aqueous sodium hydroxide was used.
O2N
HO
O
NO2
NH2
1.5 M NaOH-aq.
3
4
+
11
in excellent yields. Similarly, the hydroxylation of diacetylated derivative 7 provided 9
quantitatively, though higher concentration of sodium hydroxide and longer reaction time
were required.
The Pd-charcoal-catalyzed hydrogenation of 4 and 9 with aqueous hydrazine hydrate
in methanol provided 5 and 10 in excellent yields, respectively.
In conclusion, we have developed an efficient synthesis of 3,3ꢀ-diamino-4,4ꢀ-
dihydroxydiphenyl ether (5) and of 1,3-bis(3-amino-4-hydroxyphenoxy)benzene (10) by
the facile and direct conversion of 4,4ꢀ-diamino-3,3ꢀ-dinitrodiphenyl ether (3) and 1,3-bis(4-
amino-3-nitrophenoxy)benzene (8) into 4,4ꢀ-dihydroxy-2,2ꢀ-dinitrodiphenyl ether (4) and
1,3-bis(4-hydroxy-3-nitrophenoxy)benzene (9), respectively. The present method is envi-
ronmentally friendly, because the reactions proceed in water without organic solvents and
consume just one equivalent amount of H2O to provide the target compounds, releasing
ammonia as the sole by-product. Further studies directed toward expansion of the scope of
application and elucidation of the mechanism are in progress in our laboratory.
Experimental Section
Melting points were determined on a Yamato MP-21 melting point apparatus. 1H and 13
C
NMR spectra were recorded at 400 MHz and 100 MHz, respectively (Bruker Co. Ltd.,
Avance 400) and mass spectra were recorded on an ESI-TOF/MS Per Septive Biosystems
Mariner. A stainless-steel autoclave manufactured by Nac-autoclave Co. Ltd. (SIF-2 type,
SUS316) was used for the reactions.
4,4ꢀ-Dihydroxy-3,3ꢀ-dinitrodiphenyl Ether (4)
In a 300 mL stainless-steel autoclave were placed 4,4ꢀ-diamino-3,3ꢀ-dinitrodiphenyl ether
(9.3 g, 32.0 mmol) and 1.5 M sodium hydroxide aqueous solution (224 g, 336 mmol) and
the mixture was heated and kept at 150◦C for 1 h. TLC (silica gel 60, EtOAc/hexane 1:1)
showed that the spot of the starting compound (Rf: 0.50) had disappeared and only the spot
of 4,4ꢀ-dihydroxy-3,3ꢀ-dinitrodiphenyl ether (Rf: 0.85) appeared. The smell of ammonia
indicated the satisfactory progress of the reaction. Upon cooling the solution and addition of
28.5 g (276 mmol) of 95% sulfuric acid, the red solution turned to an orange-colored slurry.

4,4ꢀ-Dihydroxy-3,3ꢀ-dinitrodiphenyl Ether
165
Then the slurry was cooled to 5◦C and the precipitated orange-colored solid was collected.
The solid was extracted into EtOAc (100 mL) and washed with water. The combined
organic layer was dried over Na2SO4, and the solvent was removed under reduced pressure
to give 9.0 g (97%) of 4,4ꢀ-dihydroxy-3,3ꢀ-dinitrodiphenyl ether (4) as an orange-colored
solid, mp. 156–157◦C (lit:20 156–157◦C). The solid was sufficiently pure as confirmed by
its NMR, though recrystallization from methanol gave orange colored needles (91%, mp.
157–158◦C). 1H-NMR (400 MHz, DMSO): δ 7.17 (d, 2H, Ph), 7.35 (dd, 2H, Ph), 7.55 (d,
2H, Ph). 13C-NMR (100 MHz, DMSO): δ 114.42, 120.55, 126.27, 136.50, 148.10, 148.46.
m/z 291 (M-H).
1,3-bis(4-Hydroxy-3-nitrophenoxy)benzene (9)
1,3-bis(4-N-Acetylamino-3-nitrophenoxy)benzene (14.9 g, 32.0 mmol) was transformed
into 9 as described above [3.0 M NaOH aqueous solution was used instead of 1.5 M NaOH
aqueous solution. The reaction time was 5 h at 150◦C] to yield 12.3 g (100%) of 1,3-
bis(4-hydroxy-3-nitrophenoxy)benzene as an orange-colored solid, mp. 128–130◦C (lit.2
1
128.5–130◦C). H-NMR (400 MHz, DMSO): δ 6.67 (s, 1H, Ph), 6.73 (d, 2H, Ph), 7.17
(d, 2H, Ph), 7.36 (d, 2H, Ph), 7.39 (t, 1H, Ph), 7.58 (s, 2H, Ph), 10.88 (br s, 2H, OH).
13C-NMR (100 MHz, DMSO): δ 107.51, 112.37, 115.54, 120.60, 127.23, 131.28, 136.59,
147.00, 148.89, 158.48. m/z 383 (M-H).
1
The melting point, H-NMR and 13C-NMR are agreement with data given in the
literature.2
References
1. A. Iwabuchi, E. Tanaka, K. Ogawa, and K. Koike, Jp Patent 2004131386 (2004); Chem. Abstr.,
140, 375666 (2004).
2. N. Nagai and M. Senda, JP Patent 2003012611 (2003); Chem. Abstr., 138, 90638 (2003).
3. E. A. Emelin, L. B. Sokolov, and S. S. Gitis, Sintez, Analiz I Struktura Organ. Soedin., 7, 56
(1976); Chem. Abstr., 87, 101775 (1977).
4. C. J. Korpics, W. T. Jr. Smith, and J. R. Meadow, Trans. Kentucky Acad. Sci., 1961, 22, 60; Chem.
Abstr., 1962, 57, 36065.
5. R. Taniguchi, T. Yumiba, and M. Tomikawa, JP Patent 2006047627 (2006); Chem. Abstr., 144,
243390 (2006).
6. F. Toyokawa, K. Fukukawa, Y. Shibasaki, S. Ando, and M. Ueda, J. Polym. Sci., Part A: Polym.
Chem., 43, 2527 (2005).
7. T. Enoki, M. Fujimoto, and M. Murayama, PCT Int., Appl. WO2005019305 (2005); Chem. Abstr.,
142, 262690 (2005).
8. A. Izumi, M. Matsutani, A. Yoshihashi, and K. Murayama, JP Patent 2004143143, (2004); Chem.
Abstr., 140, 407263 (2004).
9. V. V. Korshak, A. A. Izyneev, and V. G. Samsonova, Republique Francaise FR 1584795 (1970);
Chem. Abstr., 73, 121257 (1970).
10. N. Yoda, M. Kurihara, S. Tohyama, K. Ikeda, N. Dokoshi, and R. Nakanishi, US Patent 3598786,
(1971); Chem. Abstr., 71, 31059 (1969).

166
Imoto et al.
11. R. J. Angelo and C. E. Berr, Republique Francaise FR 1399076 (1965); Chem. Abstr., 64, 20212
(1966).
12. M. Oesterlin, Monatsh. Chem., 57, 31 (1931).
13. M. Tomita, Yakugaku Zasshi, 53, 775 (1933); Chem. Abstr., 28, 28473 (1934).
14. A. Luttringhaus, Ann. Chim., 528, 223 (1937); Chem. Abstr., 31, 47797 (1937).
15. G. S. Stamatoff, US Patent 3290386 (1966); Chem. Abstr., 66, 37637 (1967).
16. K. W. Ritter, Ger. Offen. DE 609080 (1935); Chem. Abstr., 29, 22903 (1935).
17. H. Braus, US Patent 4326088 (1982); Chem. Abstr., 97, 23443 (1982).
18. R. Poschenrieder and E. Boettner, Ger. Offen. DE 1810179 (1969); Chem. Abstr., 71, 91074
(1969).
19. R. C. Desai, W. Han, E. J. Metzger, J. P. Bergman, D. F. Gratale, K. L. MacNaul, J. P. Berger, T.
W. Doebber, K. Leung, D. E. Moller, J. V. Heck, and S. P. Sahoo, Bioorg. Med. Chem. Lett., 13,
2795 (2003).
20. V. G. Kaloshin and I. V. Khvostov, Metody Poluch. Khim. Reaktiv. Prep., 23, 54 (1971); Chem.
Abstr., 78, 29358.
21. J. H. Burckhalter, F. H. Tendick, E. M. Jones, W. F. Holcomb, and A. L. Rawlins, J. Am. Chem.
Soc., 68, 1894 (1946).
22. B. Haussermann, Ber., 30, 738 (1897).
23. G. Koga, M. Yasaka, and Y. Nakano, Org. Prep. Proced., 1, 205 (1969).
24. C. B. Linn, US Patent 2739171 (1956); Chem. Abstr., 51, 9544 (1957).
25. E. Spaeth and K. Eiter, Ber., 74, 1854, 1863 (1941).
26. T. Kiyoura, JP Patent 2001089408 (2001); Chem. Abstr., 134, 252147 (2001).
27. T. Fujita, K. Takahata, and H. Taniguchi, JP Patent 60025946 (1985); Chem. Abstr., 102, 220561
(1985).
28. E. Biller, F. P. Schmock, and B. Haas, US Patent 3886218 (1975); Chem. Abstr., 80, 133009
(1974).
29. H. Taniguchi, H. Nakamura, and T. Fujita, JP Patent 59206326 (1984); Chem. Abstr., 102, 148876
(1985).
30. H. Heuer, R. Wehrmann, M. Erkelens, A. Meyer, and M. Mothrath, US Patent 2005250915
(2005); Chem. Abstr., 143, 460960 (2005).
31. V. Percec, M. Grigoras, R. S. Clough, and J. Fanjul, J. Polym. Sci., Part A: Polym. Chem., 33,
331 (1995).
32. R. S. Irwin, Macromolecules, 26, 7125 (1993).
33. A. Shirai, Y. Takahashi, and K. Toyofuku, JP Patent 03063179 (1991); Chem. Abstr., 115, 194275
(1991).
34. V. S. Pilyugin, Y. E. Sapozhnikov, G. V. Kiseleva, N. A. Sapozhnikova, T. P. Vorob’eva, and E.
V. Klimakova, J. Gen. Chem. USSR, 75, 1509 (2005).
35. A. R. Katritzky, Z. Yang, and D. J. Cundy, Org. Prep. Proced. Int., 25, 478 (1993).
36. J. Hlavac, M. Soural, P. Hradil, I. Frysova, and J. Slouka, J. Heterocyclic Chem., 41, 633 (2004).

4,4ꢀ-Dihydroxy-3,3ꢀ-dinitrodiphenyl Ether
167
37. A. R. Mitchell, M. D. Coburn, G. S. Lee, R. D. Schmidt, P. F. Pagoria, and P. C. Hsu, US Patent.
2005070743 (2005); Chem. Abstr., 142, 336118 (2005).
38. M. Baltas, L. Cazaux, A. D. Blic, L. Gorrichon, and P. J. Tisnes, Chem. Research (S), 284, 9
(1988).
39. N. L. Drake, H. C. Harris, and C. B. Jaeger, Jr., J. Am. Chem. Soc., 70, 168 (1948).
40. Braun, Ger. Offen. DE 3536192 (1987); Chem. Abstr., 107, 39386 (1987).
41. E. I. Bujan, A. I. Canas, and R. H. Rossi, J. Chem. Soc. Perkin 2, 1973 (2001).
42. E. I. Bujan, M. V. Remedi, and R. H. Rossi, J. Chem. Soc. Perkin 2, 969 (2000).
43. S. J. Kesten, J. Johnson, and L. M. Werbel, J. Med. Chem., 30, 906 (1987).
44. A. V. Belov and V. M. Nichvoloda, Russ. J. Org. Chem., 41, 124 (2005).

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