Facile Synthesis of Catechol Azo Dyes

Full text of DOI:10.1021/jo972151z

J . Org. Chem. 1998, 63, 4503-4505
4503
F a cile Syn th esis of Ca tech ol Azo Dyes
Sch em e 1
Kamaldin Haghbeen and Eng Wui Tan*
Department of Chemistry, University of Otago,
Dunedin, New Zealand
Received November 25, 1997
Resu lts a n d Discu ssion
Azo dyes of catechol (1,2-dihydroxybenzene) are of
interest due to their chromophoric nature and the biden-
tate character of their ortho phenolic hydroxyl groups.
These properties have made them useful for metal
Ta ble 1. Yield s (%) of Azo Com p ou n d s 2-4 Obta in ed
fr om Rea ction of th e Ap p r op r ia te Dia zon iu m Sa lt w ith
Ca tech ol, Gu a ia col, a n d P h en ol, Resp ectively
1
complexation studies and for spectroscopic measurement
2
3
4
of cation concentrations.2 Their wider utility is limited
,3
a
b
c
d
30
35
92
90
85
78
quantitative
quantitative
90
85
by a lack of generally applicable, yet efficient, methods
for their synthesis. The limitations of existing methods4-8
became obvious in our attempts to prepare catechol azo
compounds 2a -d for use as chromophoric substrates for
redox enzymes.
5
fluoroborate diazonium salts, strong acidic conditions in
6
2
a mixture of water and ethanol, and the addition of Al -
7
(
SO
4 3
) .
When the direct coupling method was used for the
synthesis of compounds 2-4, it was found that apart from
the consideration of pH the efficiency of diazo coupling
reactions is dependent on the nature of the substituents
on the aryldiazonium salts (Table 1). Aryldiazonium
salts with electron-withdrawing substituents, such as
nitro and sulfonamide, gave higher yields of diazo product
than phenyldiazonium, whereas aryldiazonium salts with
electron-donating substituents, such as methyl or meth-
oxy, gave only intractable dark material. Regardless of
the substituent on the diazonium salt, the yield of
catechol diazo compound was low and substantial amounts
of impurities were produced.
The coupling reaction of catechol with a diazonium salt
Scheme 1) is accompanied by side reactions that have
The low yields are not surprising when it is taken into
account that aryldiazonium salts undergo homolytic
dediazotization reactions under certain reducing condi-
tions. It has been reported that p-hydroquinone and
ascorbic acid can reduce diazonium salts.9 EPR studies
have shown that even under acidic conditions catechol
can reduce 4-methoxyphenyldiazonium through a one-
electron reduction to form the aryl radical intermedi-
ate.10
There are at least two factors affecting the dediazoti-
zation reaction. One factor concerns the structure of the
reducing agent, which determines the transition state of
the redox reaction. The primary factor, however, is the
reducing ability of the reducing agent. It has been shown
that molecules with oxidation potentials higher than 1
V versus normal hydrogen electrode (NHE) are poor
reducing agents for diazonium salts.11 Taking the de-
diazotization reaction into account, it was not unexpected
that phenol gave the highest yield from diazo coupling
compared to guaiacol (2-methoxyphenol) and catechol
(
not been thoroughly studied. An important aspect to
consider for catechol in a diazo coupling reaction is its
tendency to oxidize to unstable o-quinone. Oxidation of
catechol becomes increasingly rapid with increasing
alkaline pH. However, a high pH also increases the
reactivity of catechol to diazo coupling. It is the balanc-
ing of these two characteristics of catechol which leads
to compromises in the yield of reaction. Several methods
have been reported to address these two aspects of diazo
coupling with catechol. These have included alkaline
4
conditions, an acetate-buffered solution at pH 4 using
(
1) Kupletskaya, N. B.; Tikhonova, T. N.; Kashin, A. N. J . Anal.
Chem. USSR (Zh. Anal. Khim.) 1988, 43, 2070-2073.
2) Barek, J .; Berka, A.; Borek, V. Collect. Czech. Chem. Commun.
982, 47, 7 (2), 495-502.
3) Myasoedova, A. S.; Ivanov, V. M.; Busev, A. I. J . Anal. Chem.
USSR (Zh. Anal. Khim.) 1977, 32, 391-395.
4) Kokkinos, V. K.; Wizinger, R. Helv. Chim. Acta 1971, 54, 335-
38.
5) Vauquelin, G.; Verheyden, R.; Ebinger, G.; Strosberg, A. D. Clin.
Chem. 1976, 22, 1955-1961.
6) Kuznetsov, V. I.; Nemodeuk, A. A. Sb. Statei Obshch. Khim.
953, 2, 1378-1381.
7) Barkane, V.; Gudriniece, E.; Liepins, E. Khim. Seraorg. Soedin.,
Soderzh. Neftyakh Nefteprod. 1986, 4, 484-486.
8) Barton, D. H. R.; Linnell, W. H.; Senior, N. Q. J . Pharm.
Pharmacol. 1945, 18, 41-47.
(
1
(
(
3
(
(Table 1). Guaiacol, which has a peak current potential
(
1
(9) Galli, C. Chem. Rev. 1988, 88, 765-792.
(10) (a) Reszka, K. J .; Chignell, C. F. J . Am. Chem. Soc. 1993, 115,
(
7752-7760. (b) Reszka, K. J .; Chignell, C. F. Chem. Biol. Interact. 1995,
(
96, 223-234.
(11) Galli, C. J . Chem. Soc., Perkin Trans. 2 1981, 1459-1461.
S0022-3263(97)02151-8 CCC: $15.00 © 1998 American Chemical Society
Published on Web 06/05/1998

4
504 J . Org. Chem., Vol. 63, No. 13, 1998
Notes
Ta ble 2. Recover y (%) of Ca tech ol Dyes 2 Obta in ed
fr om Dem eth yla tion of Gu a ia col Dyes 3 w ith BBr 3 a n d
AlCl3/P yr id in e
BBr3
AlCl3/pyridine
2
2
2
2
a
b
c
d
incomplete reaction
incomplete reaction
72
65
80
85
72
65
ing acetonitrile13 was tried but gave no reaction after 48
1
4
h. Boron tribromide in methylene chloride could effect
the demethylation of the guaiacol azo dyes with electron-
donating groups but was completely ineffective for the
nitro and sulfonamide derivatives 3a ,3b. The method
which was applicable to all of the guaiacol dyes tested
was treatment with aluminum trichloride and pyridine
F igu r e 1. Cyclic voltammograms (SCE) of azo dyes 2b,d and
catechol, measured at pH 6.8, showing the lower oxidation
potentials of the catechol azo dyes.
3
in refluxing chloroform. The workup of the AlCl /
(
0.52 V) lower than that of phenol (0.60 V) but higher
pyridine procedure is under acidic conditions which
decreases the possibility of autoxidation. The results are
shown in Table 2.
than that of catechol (0.42 V), gave yields in diazo
coupling between that obtained for catechol and phenol.
The peak current potential for catechol is comparable to
that of p-hydroquinone. Presumably, guaiacol can reduce
diazonium salts, albeit to a lesser extent than catechol.
The dependency of the yield of diazo product on the
nature of the diazonium salt (Table 1) is in agreement
with the premise that electron-withdrawing groups in-
crease the reactivity of diazonium salts. However, these
groups also promote the ability of the diazonium salt to
accept an electron in homolytic dediazotization reac-
tions.12 The results in Table 1 show the expected effect
of the various substituents on the efficiency of the
coupling reaction between aryl diazonium salt with
phenol, guaiacol, and catechol. However, the fact that
Many factors in catechol diazo coupling reactions serve
to lower the yield of azo product. Given the nature of
catechol and of diazonium salts, these factors are gener-
ally unavoidable. The indirect method described above
affords high yields and uses reaction conditions which
allow the product to be readily purified. Moreover it is
applicable to systems with electron-donating as well as
electron-withdrawing groups.
Exp er im en ta l Section
1
Gen er a l.
in deuteriochloroform. Cyclic voltammetry was carried out at
0 °C using a 0.7-mm diameter platinum disk electrode,
H NMR spectra were recorded as dilute solutions
2
1
a ,b formed the corresponding azo compounds with
platinum wire auxiliary electrode, and aqueous KCl-saturated
calomel reference electrode (SCE).
catechol while 1c,d did not appears to contradict the
expected trend for substituent effects on homolytic de-
diazotization reactions. From peak current potentials
catechol is expected to be midway in reducing ability
between phenol and p-hydroquinone. This indicates that
diazo coupling and dediazotization reactions are in
competition in reactions between catechol and diazonium
salts. To the extent that the reactivity of the diazonium
salt is enhanced by electron-withdrawing groups, the
chance of diazo compound formation increases. By
decreasing the activity of the diazonium salt, the dedia-
zotization reaction becomes progressively dominant.
Another factor which limits the yield of catechol diazo
coupling reactions is the lower oxidation potential of
catechol azo compounds relative to that of catechol
Gen er a l P r oced u r e for P r ep a r a tion of Dia zon iu m Ch lo-
r id e Solu tion s of Su lfa n ila m id e (1b), An ilin e (1c), a n d
p-Tolu id in e (1d ). The desired aromatic amine (0.01 mol) was
dissolved in a mixture of concentrated HCl (5 mL) and distilled
water (20 mL). A solution of sodium nitrite (0.83 g, 0.012 mol)
in distilled water (5 mL) was prepared in a test tube. Sodium
nitrite solution was added dropwise to the acidic solution of
amine over 5 min at 0 °C. The mixture was stirred at 0 °C for
4
0 min.
P r oced u r e for P r ep a r a tion of Dia zon iu m Ch lor id e
Solu tion s of p-Nitr oa n ilin e (1a ). p-Nitroaniline (1.38 g, 0.01
mol) was dissolved in a mixture of methanol (20 mL) and
concentrated HCl (5 mL). Isoamyl nitrite (1.34 mL, 0.01 mol)
was added to this solution at 0 °C. A yellow precipitate
gradually appeared. The reaction mixture was kept stirring at
0
°C for 45 min.
(
Figure 1). Apparently the products may be oxidized
Gen er a l P r oced u r e for P r ep a r in g Dia zo Der iva tives of
more readily than catechol. Therefore, they are able to
dediazotize diazonium salts and lead to byproducts.
The high efficiency of the direct diazo coupling of
guaiacol led to the consideration that the guaiacol azo
dyes be used as precursors to the desired catechol azo
dyes (Scheme 1). An indirect method for the preparation
of catechol dyes has been reported previously which
involved protection of one of the hydroxyl groups of
catechol as a benzoate ester prior to coupling with
diazonium salts.8 However, this method requires alka-
line hydrolysis of the benzoyl protecting group with KOH
which promotes the autoxidation of the catechol azo dye
product.
Ca tech ol (2) th r ou gh Dir ect Dia zo Cou p lin g. The desired
deoxygenated benzonium salt solution was injected dropwise to
a deoxygenated solution of catechol (1.1 g, 0.01 mol) at 0 °C
under an N atmosphere while the pH of the reaction mixture
2
was kept between 6 and 7 by addition of the appropriate amount
of deoxygenated K CO3 (1 M) solution. The reaction mixture
2
2
was kept stirring under N at 0 °C for 30 min by which time the
product precipitated. Precipitation was driven to completion by
the addition of a few drops of dilute HCl (10%). The precipitate
was extracted with diethyl ether and evaporated to dryness
under reduced pressure. The resulting solid was washed with
heptane.
4-[(4-Nitr op h en yl)a zo]-1,2-ben zen ed iol (2a ). Using the
direct coupling procedure described above, compound 2a was
obtained in 30% yield: mp 232-234 °C; λmax 396 nm (ꢀ 13 000,
1
5
% 2-propanol-H
2
O); H NMR (acetone-d
6
) δ 7.05 (d, J ) 8.0
To cleave the methyl ether bond of the guaiacol azo
dyes, chlorotrimethylsilane with sodium iodide in reflux-
(
(
13) Bhatt, M. V.; Kulkarni, S. U. Synthesis 1983, 249-282.
14) Olah, G. A.; Narang, S. C.; Gupta, B. G. B.; Malhotra, R. J .
(12) Galli, C. J . Chem. Soc., Perkin Trans. 2 1984, 897-902.
Org. Chem. 1979, 44, 1247-1251.

Notes
J . Org. Chem., Vol. 63, No. 13, 1998 4505
Hz, 1H), 7.54 (m, 2H), 8.03 (d, J ) 9.0 Hz, 2H), 8.40 (d, J ) 9.0
quantitative yield: mp 190-192 °C; λmax 377 nm (ꢀ 25 230, 15%
+
1
Hz, 2H), 8.53 (s, 1H), 8.91 (s, 1H); LRMS (EI) 259 (M ), 242
ethanol-H
2
O); H NMR (CDCl
3
) δ 5.28 (1H, s), 6.98 (2H, d, J )
+
+
+
(M
- OH), 137 (M - C
6
H
4
NO
2
), 122 (M - C
6
H
5
N
2
O
2
).
9.1 Hz), 7.81 (2H, q, J ) 8.9 Hz), 7.88 (2H, d, J ) 8.9 Hz), 8.34
9 3 3
(2H, d, J ) 9.1 Hz). Anal. Calcd for C12H N O : C, 59.26; H,
3.73; N, 17.28. Found: C, 59.14; H, 3.56; N, 17.54.
4
-[(4-Su lfon a m id op h en yl)a zo]-1,2-ben zen ed iol (2b). Us-
ing the direct coupling procedure described above, compound 2b
was obtained in 35% yield: mp 240-242 °C; λmax 381 nm (ꢀ
4-[(4-Hyd r oxyp h en yl)a zo]ben zen esu lfon a m id e (4b). Us-
ing the general procedure described above, compound 4b was
1
1
2
2
5 730, 5% 2-propanol-H
2
O); H NMR (acetone-d
6
) δ 6.70 (s,
H), 7.02 (d, J ) 9.1 Hz, 1H), 7.50 (m, 2H), 7.94 (d, J ) 9.0 Hz,
obtained in quantitative yield: mp 254-256 °C; λmax 359 nm (ꢀ
1
H), 8.37 (d, J ) 9.0 Hz, 2H), 8.52 (s, 1H), 8.82 (s, 1H). Anal.
30 510, 15% ethanol-H
2
O); H NMR (in alkaline D
2
O) δ 6.57
Calcd for C12
H
11
N
3
O
4
S: C, 49.14; H, 3.75; N, 14.33; S, 10.92.
(2H, d, J ) 8.7 Hz), 7.59 (2H, d, J ) 6.0 Hz), 7.62 (2H, d, J )
11 3 3
6.0 Hz), 7.79 (2H, d, J ) 8.7 Hz). Anal. Calcd for C12H N O S:
C, 51.98; H, 4.00; N, 15.15; S, 11.56. Found: C, 51.84; H, 4.02;
N, 15.20; S, 11.53.
Found: C, 49.14; H, 3.96; N, 14.68; S, 10.91.
Gen er a l P r oced u r e for P r ep a r a tion of Dia zo Der iva -
tives of Gu a ia col (3). Guaiacol (1.24 g, 0.01 mol) was dissolved
in ethanol (15 mL), and the mixture was added to a solution of
4-(P h en yla zo)p h en ol (4c). Using the general procedure
K
2
CO
3
(1.4 g in 50 mL). A solution of the desired arylazonium
atmosphere
described above, compound 4c was obtained in 90% yield: mp
1
salt was added to the guaiacol solution under an N
2
149-151 °C; λmax 348 nm (ꢀ 20 350, 5% 2-propanol-H O);
H
2
at 0 °C. The resultant mixture was stirred under an N
atmosphere for 40 min at 0 °C.
2
NMR (CDCl ) δ 5.21 (1H, s), 6.93 (2H, d, J ) 8.7 Hz), 7.46-7.52
3
(3H, m), 7.86-7.90 (4H, m). Anal. Calcd for C12
10 2
H N O: C,
2
-Meth oxy-4-[(4-n itr op h en yl)a zo]p h en ol (3a ). From the
72.71; H, 5.08; N, 14.13. Found: C, 72.55; H, 4.89; N, 14.16.
4-[(4-Meth ylp h en yl)a zo]p h en ol (4d ). Using the general
procedure described above, compound 4d was obtained in 85%
general procedure described above, the reaction mixtures were
acidified by addition of cold HCl (10%) and the resulting
precipitate was dissolved in ethanol and reprecipitated by the
yield: mp 143-144 °C; λ
2
max
352 nm (ꢀ 20 800, 5% 2-propanol-
addition of water to afford 3a in 92% yield: mp 167-169 °C;
1
3
H O); H NMR (CDCl ) δ 2.44 (3H, s), 5.40 (1H, s), 6.93 (2H, d,
1
λ
4
2
max 396 nm (ꢀ 22 910, 15% ethanol-H
2
O); H NMR (CDCl
3
), δ
J ) 8.3 Hz), 7.30 (2H, d, J ) 8.3 Hz), 7.78 (2H, q, J ) 9.1 Hz),
7.86 (2H, d, J ) 9.1 Hz). Anal. Calcd for C13 N O: C, 73.56;
H, 5.70; N, 13.20. Found: C, 73.62; H, 5.45; N, 13.27.
BBr Rea ction w ith Dia zo Gu a ia col Der iva tives. An
excess of BBr (10 mol equiv) was added to a solution of the
appropriate guaiacol dye (1.0 mmol) in dried acetonitrile (25 mL)
under N The mixture was left stirring overnight at room
temperature. The resulting solution was poured slowly onto ice
300 g) which resulted in the formation of a precipitate. The
.01 (s, 3H), 6.10 (s, 1H), 7.09 (d, J ) 8.7 Hz, 1H), 7.53 (d, J )
H
12
2
.1 Hz, 1H), 7.68 (dd, J ) 8.7 Hz, 2.1 Hz, 1H), 7.98 (d, J ) 8.7
Hz, 2H), 8.36 (d, J ) 8.7 Hz, 2H). Anal. Calcd for C13
11 3 4
H N O :
3
C, 57.14; H, 4.06; N, 15.38. Found: C, 56.92; H, 4.05; N, 15.65.
-Meth oxy-4-[(4-su lfon am idoph en yl)azo]ph en ol (3b). The
same procedure as described for 3a was used to afford 3b in
0% yield: mp 241-243 °C; λmax 378 nm (ꢀ 20 120, 15% ethanol-
3
2
2
.
9
1
2 6
H O); H NMR (acetone-d ) δ 3.95 (s, 3H), 6.58 (s, 1H), 6.97 (d,
(
J ) 8.2 Hz, 1H), 7.48 (d, J ) 2.2 Hz, 1H), 7.52 (dd, J ) 8.2, 2.2
Hz, 1H), 7.88 (q, J ) 8.5 Hz, 2H), 7.98 (q, J ) 8.5 Hz, 2H). Anal.
product was extracted from the collected precipitate with diethyl
ether. The solvent was removed by evaporation under reduced
pressure, and the resulting solid was washed with heptane.
Calcd for C13
Found: C, 50.42; H, 4.41; N, 13.47; S, 10.47.
-Meth oxy-4-(p h en yla zo)p h en ol (3c). Using the general
13 3 4
H N O : C, 50.8; H, 4.26; N, 13.67; S, 10.43.
4
3
-(P h en yla zo)-1,2-ben zen ed iol (2c). Using the BBr pro-
2
cedure described above, compound 2c was obtained in 72%
procedure described above, a black precipitate was collected after
decreasing the pH of the reaction mixture to 4 by addition of
HCl (10%). This precipitate was dissolved in acetone, and an
excess amount of water (8 times in volume) was slowly added
to the acetone solution. The resulting mixture was left overnight
at room temperature to allow the product to precipitate.
yield: mp 145-147 °C, λmax 364 nm (ꢀ 15 650, 5% 2-propanol-
1
H
2
O); H NMR (acetone-d
6
) δ 7.00 (1H, d, J ) 8.2 Hz), 7.44-
7
8
1
.60 (5H, m), 7.82 (2H, dd, J ) 7.7 Hz, J ) 1.8 Hz), 8.62 (1H, s),
.91 (1H, s). Anal. Calcd for C12 : C, 67.29; H, 4.7; N,
3.08. Found: C, 67.13; H, 4.49; N, 13.11.
-[(4-Meth ylp h en yl)a zo]-1,2-ben zen ed iol (2d ). Using the
BBr procedure described above, compound 2d was obtained in
10 2 2
H N O
4
Compound 3c was obtained in 85% yield: mp 69-71 °C; λmax
3
1
3
(
4
64 nm (ꢀ 17 280, 15% ethanol-H
2
O); H NMR (CDCl
3
), δ 4.00
6
5% yield: mp 180-182 °C, λmax 364 nm (ꢀ 15 400, 5% 2-pro-
s, 3H), 5.95 (s, 1H), 7.04 (d, J ) 8.4 Hz, 1H), 7.41-7.54 (m,
H), 7.60 (q, J ) 2.2 Hz, 8.4 Hz, 1H), 7.867 (dd, J ) 8.1 Hz, 1.3
Hz, 2H). Anal. Calcd for C13 : C, 68.41; H, 5.3; N, 12.27.
Found: C, 68.18; H, 5.18; N, 12.47.
-Meth oxy-4-[(4-m eth ylp h en yl)a zo]p h en ol (3d ). From
1
2 6
panol-H O); H NMR (acetone-d ) δ 2.40 (3H, s), 6.99 (1H, d, J
)
8.4 Hz), 7.33 (2H, d, J ) 8.2 Hz), 7.40 (1H, dd, J ) 8.4 Hz, 2.1
12 2 2
H N O
Hz), 7.49 (1H, d, J ) 2.1 Hz), 7.75 (2H, d, J ) 8.2 Hz), 8.54 (s,
H), 8.83 (s, 1H). Anal. Calcd for C13 : C, 68.4; H, 5.30;
N, 12.27. Found: C, 68.30; H, 5.25; N, 12.17.
AlCl /P yr id in e Rea ction w ith Dia zo Gu a ia col Der iva -
1
12 2 2
H N O
2
the general procedure described above, the reaction mixture was
acidified by the addition of dry ice which caused precipitation
of the product. The collected dye was dissolved in ethanol and
precipitated by the addition of water. Compound 3d was
3
tives 3a ,b. To a solution of the desired guaiacol dye (1.0 mmol)
in dry chloroform (20 mL) was added an excess of anhydrous
AlCl (1 g). The resultant mixture was kept under an N
3 2
atmosphere and was heated to 50 °C. Pyridine (2.1 mL) was
added dropwise, and the mixture was refluxed for 30 h and then
cooled to room temperature. Hydrochloric acid (10%) was added,
and the product was extracted from the aqueous phase with
diethyl ether. The solvent was removed under reduced pressure,
and the resulting solid was washed with chloroform to give 2a ,b
in 80% and 85% yields, respectively.
obtained in 78% yield: mp 75-771 °C; λmax 363 nm (ꢀ 22 840,
1
1
5
7
5% ethanol-H
2
O); H NMR (CDCl
3
), δ 2.44 (s, 3H), 4.00 (s, 3H),
.92 (s, 1H), 7.04 (d, J ) 8.4 Hz, 1H), 7.29 (d, J ) 8.4 Hz, 2H),
.50 (d, J ) 2.0 Hz, 1H), 7.60 (dd, J ) 8.4 Hz, 2.0 Hz), 7.78 (d,
J ) 8.4 Hz, 2H). Anal. Calcd for C14
14 2 2
H N O : C, 69.4; H, 5.82;
N, 11.56. Found: C, 69.3; H, 5.57; N, 11.47.
Gen er a l P r oced u r e for th e P r ep a r a tion of Dia zo De-
r iva tives of P h en ol (4). Phenol (0.94 g, 0.01 mol) was
dissolved in a solution (20 mL) of sodium hydroxide (4 g, 0.1
mol) and cooled to 0 °C. The appropriate aryldiazonium salt
solution was added slowly to the phenolic solution at 0 °C. The
resultant colored mixture was stirred for 1 h at 0 °C. The
product was precipitated by addition of HCl solution (20%). For
further purification the phenolic dye was dissolved in acetone
and recrystallized by addition of water.
3
AlCl /P yr id in e Rea ction w ith Dia zo Gu a ia col Der iva -
tives 3c,d . A similar method as mentioned above for the
preparation of 2a ,b from the corresponding guaiacol dyes was
applied for 3c,d , except that acetonitrile was used in place of
chloroform. The product was extracted with diethyl ether, and
the solvent was removed under reduced pressure. The resulting
solid was washed with heptane to give 2c,d in 75% and 68%
yields, respectively.
4
-[(p-Nitr op h en yl)a zo]p h en ol (4a ). Using the general
procedure described above, compound 4a was obtained in
J O972151Z