Synthesis of 2-{2-hydroxy-3-[2-(vinyloxy)ethoxy]propoxy}-benzaldehyde and Schiff bases derived therefrom

Article abstract of DOI:10.1134/S1070428008100151

Base-catalyzed reaction of 2-hydroxybenzaldehyde with 2-{[2-(vinyloxy) ethoxy]methyl}oxirane gave 2-{2-hydroxy-3-[2-(vinyloxy)ethoxy]propoxy} benzaldehyde in 42% yield, and subsequent condensations of the product with thiosemicarbazide and primary aliphat

Full text of DOI:10.1134/S1070428008100151

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 10, pp. 1494–1496. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © B.F. Kukharev, V.K. Stankevich, G.R. Klimenko, V.A. Kukhareva, E.V. Bragin, 2008, published in Zhurnal Organicheskoi Khimii,
2008, Vol. 44, No. 10, pp. 1518–1520.
Dedicated to Full Member of the Russian Academy of Sciences
B.A. Trofimov on his 70th anniversary
Synthesis of 2-{2-Hydroxy-3-[2-(vinyloxy)ethoxy]propoxy}-
benzaldehyde and Schiff Bases Derived Therefrom
B. F. Kukharev, V. K. Stankevich, G. R. Klimenko, V. A. Kukhareva, and E. V. Bragin
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: irk_inst_chem@irioch.irk.ru
Received June 17, 2008
Abstract—Base-catalyzed reaction of 2-hydroxybenzaldehyde with 2-{[2-(vinyloxy)ethoxy]methyl}oxirane
gave 2-{2-hydroxy-3-[2-(vinyloxy)ethoxy]propoxy}benzaldehyde in 42% yield, and subsequent condensations
of the product with thiosemicarbazide and primary aliphatic amines afforded the corresponding thiosemicarba-
zone (yield 86%) and 1-{2-[(alkylimino)methyl]phenoxy}-3-[2-(vinyloxy)ethoxy]propan-2-ols (74–81%).
DOI: 10.1134/S1070428008100151
Aldehydes constitute one of the most reactive
classes of organic compounds; they possess a broad
spectrum of useful properties and are important
starting materials in organic synthesis [1]. However,
methods for the preparation of aldehydes containing
other functional groups and multiple bonds are few in
number. A general procedure for the synthesis of such
compounds may be nucleophilic addition of hydroxy
aldehydes to epoxyalkyl vinyl ethers. This reaction
could give rise to new polyfunctional derivatives
having aldehyde, hydroxy, and vinyloxy groups. Acid-
catalyzed reactions of epoxyalkyl vinyl ethers with
alcohols and phenols to give the corresponding epoxy
acetals have been reported [2]. Opening of the epoxy
group in epoxyalkyl vinyl ethers has been observed
only in their base-catalyzed reactions with ketone and
aldehyde oximes [3].
The present communication reports on the reaction
of ethylene glycol glycidyl vinyl ether (I) with 2-hy-
droxybenzaldehyde (II), which leads to the formation
of previously unknown 2-{2-hydroxy-3-[2-(vinyloxy)-
ethoxy]propoxy}benzaldehyde (III) (Scheme 1).
Molecule III contains several functional groups and
attracts interest as starting material for the synthesis of
organic compounds belonging to different classes.
When the reaction was carried out in the presence
of acid catalysts (such as trifluoroacetic, perfluoro-
butyric, or phosphoric acid), only tarry products and
Scheme 1.
CHO
CHO
OH
OH
O
O
CH2
O
O
CH2
O
+
O
I
II
III
NR
OH
O
O
RNH2 (IVa–IVd)
O
CH2
Va–Vd
R = Me (a), CH2=CHCH2 (b), t-Bu (c), NH2C(S)NH (d).
1494

SYNTHESIS OF 2-{2-HYDROXY-3-[2-(VINYLOXY)ETHOXY]PROPOXY}BENZALDEHYDE
1495
those arising from decomposition of initial vinyl ether
I were obtained. Presumably, this is the result of
decomposition of thermally unstable epoxy acetals
having 2-hydroxybenzaldehyde fragment during dis-
tillation.
hexamethyldisiloxane as internal reference. The IR
spectra were measured on a Specord 75IR spectrom-
eter from thin films (neat).
2-Hydroxybenzaldehyde, amines IVa–IVc, and
thiosemicarbazide (IVd) were commercial products.
2-{[2-(Vinyloxy)ethoxy]methyl}oxirane (I) was syn-
thesized from 2-vinyloxyethanol and 2-chloromethyl-
oxirane according to the procedure described in [5].
Taking into account that alkali metal hydroxides
could promote the Cannizzaro reaction, we used tri-
ethylamine as base catalyst. According to the GLC
data, no reaction occurred on heating an equimolar
mixture of epoxy ether I with 2-hydroxybenzaldehyde
(II) and 0.3% of triethylamine at 70°C over a period of
5 h. A probable reason is reduced reactivity of the
phenolic hydroxy group in salicylaldehyde molecule
due to formation of intramolecular hydrogen bond with
the carbonyl oxygen atom [4]. Raising the temperature
to 200°C and prolonged reaction time (2 h) resulted in
the formation of 20% of aldehyde III. The yield of III
was further improved (to 31%) by heating the reaction
mixture to 290°C and subsequent fast cooling. Alde-
hyde III was also formed in a poor yield (9%) at
290°C in the absence of a catalyst.
2-{2-Hydroxy-3-[2-(vinyloxy)ethoxy]propoxy}-
benzaldehyde (III). A mixture of 12.2 g (0.1 mol) of
2-hydroxybenzaldehyde (II), 15 g (0.104 mol) of vinyl
ether I, and 0.3 g (0.003) mol of triethylamine was
quickly heated to 290°C, cooled, and distilled under
reduced pressure. Yield 31%, bp 224–226°C (4 mm),
d420 = 1.1621, nD20 = 1.5395. IR spectrum, ν, cm–1: 3420,
3110, 3070, 3035, 2920, 2870, 1680, 1610, 1590,
1570, 1475, 1450, 1380, 1310, 1275, 1220, 1190,
1150, 1120, 1085, 1035, 1010, 975, 825, 745. 1H NMR
spectrum, δ, ppm: 3.30 br.s (1H, OH), 3.69–3.79 m
2
(6H, CH2OCH2CH2O), 3.96 d.d (1H, cis-CH=C, J =
3
2.1, Jcis = 6.8 Hz), 4.09–4.11 m (4H, OCHCH2O,
3
trans-CH=C), 6.40 d.d (1H, OCH=C, Jcis = 6.8,
In all cases, the reaction mixtures contained a large
amount of undistillable tars. Presumably, opening of
the epoxide ring by the action of phenolic hydroxy
group was accompanied by subsequent hydroxyalkyla-
tion with participation of the side-chain hydroxy group
in aldehyde III and hydroxy-containing products thus
formed. We succeeded in raising the yield of aldehyde
III to 42% by using 5 equiv of 2-hydroxybenzaldehyde
and heating the mixture for 2 h at the boiling point
which did not exceed 204°C.
3Jtrans = 14.3 Hz), 6.96 m (2H, 3-H, 5-H), 7.47 d.d (1H,
2
3
4-H, J4,5 = 6.9, J4,6 = 1.8 Hz), 7.74 d.d (1H, 6-H,
2J5,6 = 7.4, J4,6 = 1.8 Hz), 10.38 s (1H, HC=O).
3
13C NMR spectrum, δC, ppm: 67.42 (CH2OCH=),
68.97 (HOCH), 69.81 (OCH2CH2O), 70.13 (OCH2-
CHOH), 72.28 (HOCHCH2OCH2), 87.15 (=CH2),
113.07 (C3), 121.21 (C5), 125.18 (C1), 129.18 (C6),
136.07 (C4), 151.72 (OCH=), 160.97 (C2), 189.83
(O=C). Found, %: C 63.01; H 6.771. C14H18O5. Calcu-
lated, %: C 63.15; H 6.81.
Condensation of aldehyde III with methyl-, allyl-
and tert-butylamines IVa–IVc gave the corresponding
Schiff bases Va–Vc. Compound Va displayed in the 1H
NMR spectrum signals from protons in the CH3N=CH
fragment as a doublet (CH3) and quartet (CH) with
1-[2-(Methyliminomethyl)phenoxy}-3-[2-(vinyl-
oxy)ethoxy]propan-2-ol (Va). Aldehyde III, 13.3 g
(0.05 mol), was added to 78 g (0.5 mol) of 20% aque-
ous methylamine. The mixture was stirred for 2 h and
extracted with diethyl ether (3×30 ml). The extract
was dried over anhydrous K2CO3, the solvent was dis-
tilled off, and the residue was distilled under reduced
4
1
a coupling constant J of 1.4 Hz. In the H NMR
spectra of Schiff bases Vb and Vc the CH=N proton
resonated as a singlet at δ 8.42 and 8.52 ppm, respec-
tively, indicating the presence of only one Z isomer.
pressure. Yield 81%, bp 227–230°C (4 mm), nD20
=
1.5385. IR spectrum, ν, cm–1: 3390, 3115, 3075, 3045,
2930, 2880, 1630, 1610, 1595, 1575, 1480, 1445,
1395, 1360, 1310, 1290, 1240, 1190, 1150, 1130, 1100,
1
The H NMR spectrum of thiosemicarbazone Vd ob-
tained from aldehyde III and thiosemicarbazide (IVd)
contained two singlets from the CH=N proton at δ 8.58
and 8.61 ppm. Judging by the signal intensities, the
ratio of the Z and E isomers of Vd was 1:19.
1
1040, 1025, 995, 965, 805, 750. H NMR spectrum, δ,
4
ppm: 3.27 br.s (1H, OH), 3.50 s (3H, J = 1.4 Hz),
3.51 s (3H, Me), 3.69–3.85 m (7H, CH2OCH2CH2O,
2
3
cis-CH=C), 4.02 d.d (1H, trans-CH=C, J = 1.9, J =
EXPERIMENTAL
6.8 Hz), 4.18 m (3H, OCHCH2O), 6.48 d.d (1H,
1
The H and 13C NMR spectra were recorded at
3
3
OCH=C, Jcis = 6.8, Jtrans = 14.3 Hz), 6.98 m (2H,
2
3
26°C on a Bruker DPX-400 instrument at 400 and
100 MHz, respectively, using CDCl3 as solvent and
3-H, 5-H), 7.34 d.d (1H, 4-H, J4, 5 = 7.0, J4, 6 =
1.5 Hz), 7.72 d.d (1H, 6-H, J5,6 = 7.6, J4,6 = 1.5 Hz),
2
3
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008

KUKHAREV et al.
1496
4
13
8.54 q (1H, N=CH, J = 1.4 Hz). C NMR spectrum,
δC, ppm: 48.42 (CH3), 67.33 (CH2OC=), 68.92
(HOCH), 70.04 (OCH2CH2OC=), 70.88 (OCH2-
CHOH), 72.30 (HOCHCH2OCH2), 86.92 (=CH2),
113.97 (C3), 121.52 (C5), 125.26 (C1), 128.99 (C6),
131.67 (C4), 151.72 (OCH=), 157.94 (C2), 160.65
(N=C). Found, %: C 64.32; H 7.43; N 4.91. C15H21NO4.
Calculated, %: C 64.50; H 7.58; N 5.01.
into diethyl ether (3×30 ml), the extract was dried over
anhydrous K2CO3, and the solvent was evaporated.
The residue was a very viscous uncrystallizable tar.
Yield 86%. IR spectrum, ν, cm–1: 3350, 3310, 3180,
3080, 3050, 2930, 2880, 1690, 1640, 1615, 1600, 1525,
1490, 1460, 1370, 1320, 1295, 1260, 1200, 1170, 1120,
1
1050, 975, 880, 820, 765. H NMR spectrum, δ, ppm:
3.61–3.84 m (6H, CH2OCH2CH2O), 3.93–4.24 m (7H,
cis-CH=C, NCH2, OCHCH2O, trans-CH=C), 6.43 d.d
(1H, OCH=C, Jcis = 6.7, Jtrans = 14.3 Hz), 6.82–
Schiff bases Vb and Vc (general procedure).
A mixture of 0.05 mol of aldehyde III, 0.15 mol of
amine IVb or IVc, and 50 ml of diethyl ether was kept
for 20 h over anhydrous K2CO3. The product was
isolated by vacuum distillation.
3
3
6.92 m (2H, 3-H, 5-H), 7.21–7.31 m (5H, 4-H, OH,
2
NH, NH2), 7.73 d (1H, 6-H, J5,6 = 7.6 Hz), 8.58 s
(0.05H, HC=N, Z isomer), 8.61 s (0.95H, HC=N,
E isomer). 13C NMR spectrum, δC, ppm: 67.35 (OCH2-
CH2OC=), 69.05 (HOCH), 69.83 (OCH2CH2OC=),
69.91 (OCH2CHOH), 72.27 (HOCHCH2OCH2), 87.11
(=CH2), 112.03 (C3), 121.08 (C5), 126.03 (C1), 128.98
(C6), 131.92 (C4), 141.45 (N=C), 151.59 (OC=),
157.67 (C2), 177.36 (S=C). Found, %: C 53.12;
H 6.12; N 12.21; S 9.38. C15H21N3O4S. Calculated, %:
C 53.08; H 6.24; N 12.38; S 9.45.
1-[2-(Allyliminomethyl)phenoxy]-3-[2-(vinyloxy)-
ethoxy]propan-2-ol (Vb). Yield 74%, bp 232–235°C
(2 mm), nD20 = 1.5338. IR spectrum, ν, cm–1: 3400,
3115, 3080, 3045, 3020, 2940, 2880, 1640, 1615,
1605, 1595, 1585, 1485, 1460, 1405, 1445, 1370,
1310, 1250, 1200, 1150, 1145, 1045, 980, 815, 750.
1H NMR spectrum, δ, ppm: 3.23 br.s (1H, OH), 3.65–
3.83 m (8H, CH2OCH2CH2O, CH2CH=), 3.95–4.18 m
(7H, cis-CH=C, NCH2, OCHCH2O, trans-CH=C),
5.45 m (2H, CCH=CH2), 6.12 m (1H, CCH=), 6.46 d.d
REFERENCES
3
3
(1H, OCH=C, Jcis = 6.8, Jtrans = 14.3 Hz), 6.91–
7.62 m (4H, Harom), 8.42 s (1H, HC=N). Found, %:
C 66.45; H 7.69; N 4.35. C17H23NO4. Calculated, %:
C 66.86; H 7.59; N 4.59.
1. Roberts, J.D. and Caserio, M., Basic Principles of
Organic Chemistry, New York: W.A. Benjamin, 1975,
2nd ed. Translated under the title Osnovy organicheskoi
khimii, Moscow: Mir, 1978, vol. 1, p. 457; Comprehen-
sive Organic Chemistry, Barton, D. and Ollis, W.D.,
Eds., Oxford: Pergamon, 1979, vol. 1. Translated under
the title Obshchaya organicheskaya khimiya, Moscow:
Khimiya, 1982, vol. 2, p. 488; Khimicheskaya entsiklope-
diya (Chemical Encyclopedia), Knunyants, I.L., Ed.,
Moscow: Sovetskaya Entsiklopedia, 1988, vol. 1, p. 196.
1-[2-(tert-Butyliminomethyl)phenoxy]-3-[2-(vinyl-
oxy)ethoxy]propan-2-ol (Vc). Yield 77%, bp 235–
238°C (2 mm), nD20 = 1.5285. IR spectrum, ν, cm–1:
3400, 3110, 3070, 3030, 2960, 2920, 2870, 1630, 1615,
1595, 1580, 1485, 1445, 1365, 1310, 1280, 1250, 1120,
1
1100, 1030, 975, 930, 900, 865, 800, 750. H NMR
2. Nedolya, N.A. and Trofimov, B.A., Zh. Org. Khim., 1985,
spectrum, δ, ppm: 1.31 s (9H, CH3), 3.65–3.87 m (7H,
OH, CH2OCH2CH2O), 3.91–4.24 m (7H, cis-CH=C,
NCH2, OCHCH2O, trans-CH=C), 6.48 d.d (1H,
OCH=C, Jcis = 6.7, Jtrans = 14.3 Hz), 6.87–7.61 m
(4H, Harom), 8.52 s (1H, HC=N). Found, %: C 67.43;
H 8.51; N 4.28.C18H27NO4. Calculated, %: C 67.26;
H 8.47; N 4.36.
vol. 21, p. 271.
3. Nedolya, N.A., Khil’ko, M.Ya., Mikhaleva, A.I., and
Trofimov, B.A., Zh. Org. Khim., 1987, vol. 23, p. 1426;
Kukharev, B.F., Stankevich, V.K., Klimenko, G.R., and
Shaposhnikova, A.N., Russ. J. Org. Chem., 2007, vol. 43,
p. 181.
4. Comprehensive Organic Chemistry, Barton, D. and
Ollis, W.D., Eds., Oxford: Pergamon, 1979, vol. 1.
Translated under the title Obshchaya organicheskaya
khimiya, Moscow: Khimiya, 1982, vol. 2, p. 175.
5. Trofimov, B.A., Stankevich, V.K., Belozerov, L.E.,
Kukharev, B.F., Klimenko, G.R., Nedolya, N.A., Khari-
tonov, V.I., Popov, D.A., Tyun’kov, O.V., and Moshchen-
ko, Yu.A., USSR Inventor’s Certificate no. 1129208,
1982; Byull. Izobret., 1984, no. 46.
3
3
2-{2-Hydroxy-3-[2-(vinyloxy)ethoxy]propoxy}-
benzaldehyde thiosemicarbazone (Vd). A solution of
4.6 g (0.05 mol) of thiosemicarbazide in 150 ml of
water was heated to 80°C, and a solution of 13.3 g
(0.05 mol) of aldehyde III in 50 ml of ethanol was
added under stirring. After cooling to room tempera-
ture, a viscous oily material separated. It was extracted
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 10 2008