One-pot oxidation of azomethine compounds into arenecarboxylic acids

Article abstract of DOI:10.1081/SCC-100105891

Aromatic azomethine compounds, such as aldazines 1, aldoximes 7 and tosylhydrazones 8 oxidized with 30% hydrogen peroxide in the presence of poly(bis-1,2-phenylene) diselenide (6) as catalyst produce arenecarboxylic acids 2 mostly in high to excellent yields. The presented one-pot procedure has a synthetic value.

Full text of DOI:10.1081/SCC-100105891

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ONE-POT OXIDATION OF AZOMETHINE COMPOUNDS
INTO ARENECARBOXYLIC ACIDS
Mirosław Giurg a , Samy B. Said b , Ludwik Syper a & Jacek Młochowski c
a Institute of Organic Chemistry, Wrocław University of Technology, Biochemistry and
Biotechnology, Wroclaw, 50 370, Poland
b Faculty of Sciences, Chemistry Department, Mansoura University, P.O. Box 60, New
Damietta, Egypt
c Institute of Organic Chemistry, Wrocław University of Technology, Biochemistry and
Biotechnology, Wroclaw, 50 370, Poland
Published online: 16 Aug 2006.
To cite this article: Mirosław Giurg , Samy B. Said , Ludwik Syper & Jacek Młochowski (2001): ONE-POT OXIDATION OF
AZOMETHINE COMPOUNDS INTO ARENECARBOXYLIC ACIDS, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:20, 3151-3159
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SYNTHETIC COMMUNICATIONS, 31(20), 3151–3159 (2001)
ONE-POT OXIDATION OF
AZOMETHINE COMPOUNDS INTO
ARENECARBOXYLIC ACIDS
Miroslaw Giurg,1 Samy B. Said,2
Ludwik Syper,1 and Jacek Mlochowski1,
*
1Institute of Organic Chemistry, Biochemistry and
Biotechnology, Wroclaw University of Technology,
50 370 Wroclaw, Poland
2Mansoura University, Faculty of Sciences,
Chemistry Department, New Damietta,
P.O. Box 60, Egypt
ABSTRACT
Aromatic azomethine compounds, such as aldazines 1, aldox-
imes 7 and tosylhydrazones 8 oxidized with 30% hydrogen
peroxide in the presence of poly(bis-1,2-phenylene) diselenide
(6) as catalyst produce arenecarboxylic acids 2 mostly in high
to excellent yields. The presented one-pot procedure has a
synthetic value.
*Corresponding author.
3151
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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GIURG ET AL.
The carboxylic acids are group of compounds important for industrial
and preparative organic chemistry.1,2 One of the simplest method applied
for their synthesis is oxidation of the carbonyl compounds,2,3 also
with hydrogen peroxide in the presence of selenium compounds, such as
selenium(IV) oxide,4 benzeneseleninic acid5 and poly(bis-9,10-anthracenyl)
diselenide (PADS).6
The main goal of the work presented here was to extend the
methodology of arenecarboxylic acids synthesis through hydrogen peroxide
oxidation of aromatic aldehyde derivatives having azomethine moiety
C¼N instead of carbonyl group. This approach seems to be attractive
because azomethine compounds are easily available crystalline species
and some of them (e.g. azines, oximes and hydrazones) can also be obtained
by the particular ways other than direct synthesis from aldehydes and
ketones.7 Moreover, they also play an important role in the protecting
and deprotecting procedures of carbonyl compounds.8 According to the
tendency of contemporary organic chemistry the oxidant should be easily
available, cheap and environmentally friendly. The hydrogen peroxide fulfill
these requirements, although in most of the reactions is used in the presence
of suitable catalyst.9
Continuing our studies on hydrogen peroxide oxidation catalyzed by
selenium compounds,4,6,9,10 we have found that oxidation of benzaldazine
(1a) in THF11 leads to the mixture of benzoic acid (2a), benzaldehyde (3),
benzyl alcohol (4) and benzyl benzoate (5) (Scheme 1).
Scheme 1.
A variety of diaryl diselenides and other selenium compounds such
as selenium(IV) oxide, 2-phenylbenzisoselenazol-3(2H)-one (ebselen),
and benzene-1,2-diseleninic acid were examined as catalyst in this model
reaction.12

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3153
The highest total yield (95%) of the oxidation products 2a, 3 and 5 was
found when poly(bis-1,2-phenylene)diselenide (6) was used as catalyst. The
major product was desired acid 2a (79%), accompanied by the aldehyde 3
(16%) and trace amounts of the alcohol 4 and ester 5. Thus, diselenide 6 was
selected as a catalyst for preparative hydrogen peroxide oxidation of various
aromatic aldazines (1), aldoximes (7) and tosylhydrazones (8) (Scheme 2).
The reaction was carried out in THF under reflux for the period from 6
hours to 10 days depending on the substrate used (Table 1).
Scheme 2.
Oxidation of the aromatic azomethine compounds having no substi-
tuents 1a,b, 7a,b, 8a,b and these ones bearing alkyl group 1c–e, 7c–e, 8c–e
and electron withdrawing substituents 1f–i, 1k–n, 1p, 7f–p, 8f–p gave corre-
sponding carboxylic acid despite of the type of azomethine group. When the
substituent was present in ortho-position 1l–n, 7l–n, 8l–n or two substituents
were in both of ortho-positions 1p, 7o,p, 8o,p the reaction proceded more
slowly. In all these cases, arenecarboxylic acids (2a–p) were isolated in yields
above 90%.
When the electron-donating methoxy groups were present in the ortho
or para positions of aromatic ring, the yields of acid 2q–s were substantially
lower (15–68%). The acids were accompanied with tarry mixtures of the
phenols and the products of their subsequent transformations.
Exceptionally, oxidation of azine 1t, oxime 7t and tosylhydrazone
8t lead to 1-naphthoic acid (2t) and (1-oxo-1,3-dihydroisobenzofuran-1-
yl)acetic acid (9)15 resulted from oxidative transformations of the generated

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GIURG ET AL.
Table 1. Oxidation of Aldazines 1, Aldoximes 7, and Tosylohydrazones 8 into
Carboxylic Acids 2
Yield of Acid 2 [%]
(Reaction Time [h])
Product 2
from 1
from 7
from 8
Mp., (Ref.14)
120–122
185–186
179–180
117–118
164–166
184–186
240
a
b
c
d
e
f
99 (18)
99 (72)
99 (60)
96 (72)
97 (75)
94 (48)
91 (38)
99 (20)
95 (24)
99 (10)
99 (36)
100 (42)
100 (70)
92 (40)
100 (24)
92 (24)
98 (28)
96 (24)
94 (38)
96 (42)
100 (63)
90 (63)
98 (145)
92 (240)
100 (72)
15 (41)
23(65)
98 (9)
97 (20)
96 (18)
95 (15)
93(16)
98 (12)
92 (15)
90 (10)
98 (8)
94 (12)
98 (10)
96 (8)
98 (85)
100 (48)
94 (144)
99 (52)
41 (6)
(121–123)
(185–187)
(180–182)
(117–120)
(165–167)
(184–187)
(239–241)
(252–254)
(221–223)
(239–245)
(140–142)
(146–148)
(138–140)
(157–160)
g
h
i
254–256
220–221
238–239
140–141
142–145
140–141
156–159
142–14–31(4154)3
157–158
99–100
a
–
j
k
l
100 (40)
93(86)
m
n
o
p
q
r
98 (140)
100 (240)
b
–
100 (160)
18 (50)
25 (50)
33 (40)
24c (115)
92 (41)
91 (66)
(159–161)
(99–100)
40 (16)
68 (20)
16c (24)
99 (14)
90 (24)
181–183
168–170
159–161
104–105
147–148
(182–185)
(168–171)
(160–162)
(106–108)
(149–150)
s
16 (50)
30c (115)
96 (42)
94 (28)
t
u
v
aThe substrate 1j was completely insoluble in THF-H2O2; bafter 10 days only a little
reaction progress was observed; caccompanied with (1-oxo-1,3-dihydroisobenzo-
furan-1-yl)-acetic acid (915 24–70% yield).
in situ 1-naphtol.16 3-Methoxy, and 3-phenoxybenzaldazines 1u–v, related
oximes 7u,v and tosylhydrazones 8u,v were oxidized exclusively to acids
2u,v (90–99%).
EXPERIMENTAL
All isolated acids 2 presented in Table were identified after their recrys-
tallization from ethanol-water (2a,k,l,q,v), methanol-water (2c–e, 2n–p, 2u),
chloroform (2b,f,j,r), THF-water (2g–i), by their melting points (Digital

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3155
Melting Point Apparatus Electrothermal IA 91100) and by comparison
of their 1H NMR data (CDCl3 or DMSO-d6, TMS, Bruker DRX 300
Spectrometer) with these reported in ref.19 Commercially available starting
materials Aldrich and Fluka of purity above 95% were used without
additional purification. Aldazines 1a–v and aldoximes 8a–v were obtained
from corresponding aldehydes 3a–v by their treating with hydrazine
or hydroxylamine respectively, according to the procedures reported in
ref.20 Tosylhydrazones 8a–v were prepared with modified procedure
reported in ref.21,22
Poly(bis-1,2-phenylene) Diselenide (6)23
The solution of lithium diselenide prepared according to ref.6 from
lithium (0.75 g, 0.10 mol) and selenium (8.0 g, 0.10 mol) in HMPT (30 ml)
was added to a stirred solution of 1,2-diiodobenzene26 (16 g, 0.048 mol) in
THF (40 ml). Tetrahydrofuran was distilled off and the reaction was con-
tinued at 100ꢀC for 6 h, and then at 130ꢀC for 24 h. After cooling, methanol
(200 ml) was added to the reaction mixture and it was stirred at room
temperature for 24 h. The product 6 was filtered off and washed sub-
sequently with methanol and dried in air. Yellow-brown powder. Yield
10.21 g (90%), softening at 73–150ꢀC, IR (KBr) cmꢁ1 3039, 2956, 2849
(CH), 1558, 1473, 1463, 1432 (C-C aromatic) 742 (CH aromatic out of
plane) 689, 642 (CSe). Sparingly soluble in the solvents used for NMR
spectroscopy. Found: C, 30.25; H, 2.01. (C6H4Se2)n, (234.03)n requires C,
30.79; H, 1.72.
Oxidation of Aldazines (1). General Procedure
The solution or suspension of aldazine 1a–i, 1k–v (10 mmol) in
tetrahydrofuran (20 ml), 30% hydrogen peroxide (6 ml, 60 mmol) and dis-
elenide 6 (0.024 g, 0.10 mmol), was magnetically stirred and slowly heated
to gently reflux (ca. 1 h). The reaction progress was monitored by TLC using
dichloromethane as an eluent, and it was continued until the spot of parent
aldehyde 3 vanished. When the reaction was prolonged above 12 h, the
additional portions of hydrogen peroxide (2.5 ml) and THF (in the
amount made the reaction homogenous) were added after each 12 h
period. The acids (2g–i) crystallized directly after the cooling of
the reaction mixture in 60–80% yield and were filtered off. The filtrates
(2g–i) or the reaction mixtures containing acids 2a–f, 2k–n, 2p–v were
treated with a pinch of Pt/C and then the solution of NaHCO3 (5g) and

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3156
GIURG ET AL.
NaCl (15 g) in water (200 ml) was added stepwise until evolution of carbon
dioxide ceased. The solution was washed with chloroform (3 ꢂ 25 ml)
and the layers were separated. The aqueous layer was acidified with
concentrated hydrochloric acid (pH 1–2) and it was extracted with diethyl
ether (3 ꢂ 150 ml) (2i) or with chloroform (100 ml and 4 ꢂ 25 ml) (2a–h,
2k–n, 2p–v). The extract was dried over anhydrous sodium sulfate,
the solvent was removed in vacuo and the residue was a pure acid 2a–k,
2q–s, 2u, 2v. The acids 2i–n, 2p, 2t were purified on the column with
silicagel (70–230 mesh) using hexane-ethyl acetate-acetic acid as an eluent.
The additional amounts of the acids soluble in chloroform (2b–e)
were obtained from chloroform layer by alkaline extraction as described
above.
Oxidation of Aldoximes (7). General Procedure
The solution of aldoxime 7a–v, (20 mmol) in tetrahydrofuran (30 ml),
30% hydrogen peroxide (10 ml, 0.1 mol) and diselenide 6 (0.047 g,
0.20 mmol), was magnetically stirred and slowly heated to gently reflux
(ca. 1 h) and the reaction was carried out in the same manner as described
for the azines 1. After the reaction finished, the acids (2g–i) crystallized
directly after the cooling of the reaction mixture and were filtered off. The
filtrates (2g–i) or the reaction mixtures containing acids 2a–f, 2j–v were
worked up as described for the azines 1. The acid was purified chromato-
graphically.
Oxidation of Tosylhydrazones (8). General Procedure
To the magnetically stirred solution of tosylhydrazone 8a–x (20 mmol)
in tetrahydrofuran (70 ml), containing suspended diselenide 6 (0.094 g,
0.40 mmol), 30% hydrogen peroxide (20 ml, 0.2 mol) was added dropwise.
The mixture was slowly heated to gently reflux (ca. 1 h) and the reaction was
carried out in the same manner as described for the azines 1. When the
reaction was prolonged above 24 h (for 8m–p), the additional portions of
hydrogen peroxide (20 ml) were added each day. After the reaction finished,
a pinch of Pt/C was added, the reaction mixture was left stirred at room
temperature overnight and then it was treated with solution of NaHCO3
(5 g) and NaCl (15 g) in water (200 ml). The acids 2a–f, 2j–v were isolated in
the same manner as described for oxidation of aldazines 1. The acids 2g–i
crystallized from the solutions concentrated in vacuo to a half of the volume
and cooled to ꢁ10ꢀC.

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selective.
12. The diselenides tested as catalyst, such as 2- and 4-pyridyl, 6-methyl-2-
pyridyl, 2-quinolyl, 5-pyrimidinyl, 2- and 4-nitrophenyl and poly(bis-9,
10-anthracenyl) diselenide (PADS) were synthesized according to the
ref.6,13 Synthesis of diselenide RSeSeR (R: 3-nitro-2-pyridyl, 2-nitrio-
4(trifluoromethyl)phenyl, 2-(trifluoromethyl) phenyl (bis-1,4-pheny-
lene) and benzene-1,2-diseleninic acid will be published in due course.

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GIURG ET AL.
Selenium dioxide and diphenyl diselenide were purchased from
Aldrich. Poly (bis-1,2-phenylene) diselenide (6) was synthesized in the
way reported.
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15. The compound 9 was isolated in the 24% yield16 from mixture 2t and 9
by using column chromatography. Colorless prisms, mp ¼
149.5–150.5ꢀC (toluene), lit.17 mp ¼ 150–151ꢀC. IR (KBr): 3500–
1
2200 cmꢁ1 (COOH), 1759 and 1709 cmꢁ1 (C¼O). H NMR (CDCl3):
8.30 (s, 1H, COOH), 7.93 (d, 1H, J ¼ 7.5 Hz, ArH), 7.72 (t, 1H,
J ¼ 7.5 Hz, ArH), 7.58 (t, 1H, J ¼ 7.5 Hz, ArH), 7.54 (d, 1H,
J ¼ 7.5 Hz, ArH), 5.80 (t, 1H, J ¼ 6.5 Hz, CH), 2.99 (d, 2H,
J ¼ 6.5 Hz, CH2). 13C NMR data are identical as these reported in ref.18
16. The compd. 9 was also obtained in 26% yield by the oxidation of
1-naphtol.
17. Gabriel, S.; Michael, A. Chem. Ber. 1877, 10, 1551.
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22. Said, S.B. private communication, to be published.
23. Toxicity of poly(bis-1,2-phenylene) diselenide (6) is unknown.
According to know rules its toxicity should be low.24,25 Nevertheless
avoid skin contact by use of gloves. All manipulations should be done
in a hood.
24. Shamberger, R.J. Biochemistry of Selenium, Plenum Press, New York,
1983, p. 203.
25. Information on Uses, Handling and Storage of Selenium, Selenium-
Tellurium Development Association, Grimberg (Belgium), 1993.

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26. 1,2-Diiodobenzene was easily prepared (85% yield) in molar scale by
conversion of 2-iodoaniline to diazonium salt by treatment with acidic
sodium nitrite in acetic acid solution and subsequent reaction with
aqueous sodium iodide. From the solution 1,2-diiodobenzene was
extracted with dichloromethane and purified by destillation in vacuo
at 152ꢀ/15 mm.
Received in the Netherlands January 2, 2001

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