6262
R. W. Sabnis / Tetrahedron Letters 50 (2009) 6261–6263
Table 1
color-change concept. Currently, we are investigating the synthesis
A facile synthesis of phthalein indicator dyes 3a–m
of novel dye libraries, details of which will be published in due
course. These dyes have potential applications in medical, coatings,
and electronics field.
R6
R6
HO
R5
R5
OH
R2
O
R6
O
HO
R2
R5
O
R2
Acknowledgments
O
2
R3
O
+
methanesulfonic acid
R3
The author thanks the Department of Chemistry, University of
Minnesota, for recording FTIR, NMR, and mass spectra.
R3
3
1
2
References and notes
Entry
R2
R3
R5
R6
Producta
Yield (%)
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1
2
3
4
5
6
7
8
9
10
11
12
13
H
CH3
C2H5
iso-Propyl
sec-Butyl
OCH3
C6H5
CH3
iso-Propyl
CH3
OCH3
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
CH3
CH3
H
H
H
H
H
H
H
H
H
H
H
3a
3b
3c
3d
3e
3f
3g
3h
3i
94
92
81
83
77
79
94
85
90
91
84
89
73
H
CH3
OCH3
iso-Propyl
CH3
3j
3k
3l
iso-Propyl
CH3
CH3
H
3m
a
The reaction was conducted in anhydrous conditions.
yields (upto 73–94%) of the target phthalein dyes 3a–m. Phthalein
indicator dyes 3a–m formed by this method are highly pure show-
ing single spot on TLC (Thin Layer Chromatography) and no by-
products were detected.
5. Baeyer, A. Justus Liebigs Ann. Chem. 1880, 202, 36–140.
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Patent 4252725, 1981; Chem. Abstr. 1981, 94, 208695.; (e) Hubacher, M. H. J. Am.
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Stefan, M. Rom. RO 91178, 1987; Chem. Abstr. 1988, 108, 112216.; (g) McKenna,
J. F.; Sowa, F. J. J. Am. Chem. Soc. 1938, 60, 124–125; (h) Orndorff, W. R.; Murray,
R. R. J. Am. Chem. Soc. 1917, 39, 679–697; (i) Gronowska, J. Rocz. Chem. 1959, 33,
191–195; Chem. Abstr. 1959, 53, 94608.; (j) Jaczewski, Z.; Karminski, W.;
Kasprzyk, J.; Atamanczuk, B. Przem. Chem. 1982, 61, 93–95; Chem. Abstr. 1982,
97, 127423.; (k) Kasprzyk, J.; Wagner, A.; Karminski, W.; Jaczewski, Z.; Langier,
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108001.
7. (a) Rangnekar, D. W.; Kulkarni, V. S.; Ranade, P. V.; Sabnis, R. W. Synth. Commun.
2007, 37, 425–430; (b) Jachak, M. N.; Avhale, A. B.; Toche, R. B.; Sabnis, R. W. J.
Heterocycl. Chem. 2007, 44, 343–347; (c) Toche, R. B.; Jachak, M. N.; Dalvi, T. S.;
Sabnis, R. W.; Junek, H.; Kappe, T. Org. Prep. Proced. Int. 1998, 30, 367–372; (d)
Sabnis, R. W.; Rangnekar, D. W. J. Heterocycl. Chem. 1992, 29, 1027–1029.
8. (a) Deligeorgiev, T. G.; Zaneva, D. A.; Kim, S. H.; Sabnis, R. W. Dyes Pigm. 1998, 37,
205–211; (b) Timcheva, I. I.; Maximova, V. A.; Deligeorgiev, T. G.; Gadjev, N. I.;
Sabnis, R. W.; Ivanov, I. G. FEBS Lett. 1997, 405, 141–144; (c) Sabnis, R. W.;
Deligeorgiev, T. G.; Jachak, M. N.; Dalvi, T. S. Biotech. Histochem. 1997, 72, 253–
258; (d) Rangnekar, D. W.; Sabnis, R. W. J. Chem. Technol. Biotechnol. 1993, 56,
401–405; (e) Sabnis, R. W.; Rangnekar, D. W. J. Heterocycl. Chem. 1992, 29, 65–
68; (f) Sabnis, R. W.; Kazemi, G.; Rangnekar, D. W. Bull. Chem. Soc. Jpn. 1991, 64,
3768–3770.
It is noteworthy that the starting materials and catalyst are
readily available and highly economical. The reaction time is short
(5 h) and work-up is easy. The products can be easily purified by
recrystallization using charcoal treatment. The products are
formed in excellent yields (Table 1). The phthalein compounds
generated by this elegant method are pH indicators or acid–base
indicators. They are colorless in acidic pH and deeply colored in
alkaline pH. They exhibited red, pink, magenta, purple, violet, blue,
and teal colors in basic pH. The color-change transition of phtha-
lein indicator dyes is given in Table 2. This facile synthetic method-
ology can be applied to manufacture phthalein indicator dyes on
an industrial scale in excellent yield and in high purity.
In conclusion, we have successfully developed an elegant, one-
pot synthesis for phthalein indicator dyes using readily available
and economical starting materials in the presence of methanesulf-
onic acid as a catalyst. The beauty of this method lies in the fact
that the synthetic method offers short reaction time, ease of puri-
fication through crystallization, and high yields on an industrial
scale. There is a huge scope to expand this approach for advancing
9. General procedure: A mixture of phenol 1 (0.133 mol) and phthalic anhydride 2
(0.074 mol) in methanesulfonic acid (0.416 mol) was stirred and heated at 90 °C
for 5 h. The reaction mixture was cooled to room temperature and slowly added
to ice-water when the product precipitated. The product was filtered, throughly
washed with water, and dried. The crude product was purified by
Table 2
Color-change transition of phthalein indicator dyes 3a–m
Product
Color-change transition (pH: acidic to alkaline)
recrystallization from
a suitable solvent with charcoal treatment-furnished
pure phthalein dye 3.
3a
3b
3c
3d
3e
3f
3g
3h
3i
Colorless to pink
Colorless to red
Compound 3a: mp 261–263 °C (from methanol); FTIR (KBr):
m 3383, 3292, 2954,
1738, 1611, 1266 cmÀ1 1H NMR (300 MHz, DMSO-d6): d 9.65 (s, 2H, 2OH), 6.79
;
Colorless to magenta
Colorless to pink
Colorless to purple
Colorless to violet-blue
Colorless to purple
Colorless to indigo-blue
Colorless to blue
Colorless to violet
Colorless to teal
Colorless to violet
Colorless to teal
(dd, 4H, aromatic), 7.10 (dd, 4H, aromatic), 7.64–7.91 (m, 4H, aromatic) ppm;
Mass spectra (70 eV): m/z 318 (M+). Anal. Calcd for C20H14O4: C, 75.47; H, 4.40.
Found: C, 75.49; H, 4.44.
Compound 3b: mp 221–223 °C (from ethanol); FTIR (KBr):
m 3463, 1739, 1714,
1612, 1276 cmÀ1 1H NMR (300 MHz, DMSO-d6): d 9.58 (s, 2H, 2OH), 2.08 (s, 6H,
;
2CH3), 6.78–6.98 (m, 6H, aromatic), 7.63–7.89 (m, 4H, aromatic) ppm; Mass
spectra (70 eV): m/z 346 (M+). Anal. Calcd for C22H18O4: C, 76.30; H, 5.20. Found:
C, 76.27; H, 5.19.
3j
3k
3l
Compound 3c: mp 145–148 °C (from ethyl acetate/petroleum ether, 1:1); FTIR
(KBr):
m ;
3389, 1783, 1718, 1605 cmÀ1 1H NMR (300 MHz, DMSO-d6): d 9.54 (s,
2H, 2OH), 2.43–2.50 (q, 4H, 2CH2), 1.00–1.05 (t, 6H, 2CH3), 6.74–6.96 (m, 6H,
aromatic), 7.57–7.89 (m, 4H, aromatic) ppm; Mass spectra (70 eV): m/z 374
3m