Reaction of resorcinol and its derivatives with urea acetals

Article abstract of DOI:10.1134/S107036320906022X

Reaction of 2-methylresorcinol and pyrogallol with urea acetals of various structures was studied. Depending on the structure of the acetal used, reaction was established to result in eiter calix[4]resorcinols containing urea fragment or in imidazolidin-2

Full text of DOI:10.1134/S107036320906022X

ISSN 1070-3632, Russian Journal of General Chemistry, 2009, Vol. 79, No. 6, pp. 1163–1166. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © M.S. Khakimov, A.S. Gazizov, A.R. Burilov, M.A. Pudovik, A.I. Konovalov, 2009, published in Zhurnal Obshchei Khimii, 2009,
Vol. 79, No. 6, pp. 991–994.
Reaction of Resorcinol and Its Derivatives with Urea Acetals
M. S. Khakimov, A. S. Gazizov, A. R. Burilov, M. A. Pudovik, and A. I. Konovalov
Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences,
ul. Arbuzova 8, Kazan, 420088 Tatarstan, Russia
e-mail: burilov@iopc.knc.ru
Received November 10, 2008
Abstract—Reaction of 2-methylresorcinol and pyrogallol with urea acetals of various structures was studied.
Depending on the structure of the acetal used, reaction was established to result in eiter calix[4]resorcinols
containing urea fragment or in imidazolidin-2-one derivatives.
DOI: 10.1134/S107036320906022X
involving urea fragments, we used 1-(4,4-diethoxy-
butyl)-3-phenylurea I obtained by reaction of 4,4-
diethoxybutylamine with phenylisocyanate, in the
reaction with resorcinol derivatives.
According to published data, the calixarene
containing urea fragments can be used as anion
selective complexing agents [1], as building blocks for
molecular container constructions carcerands and
carceplexes [2], and as stationary phases for the liquid
chromatography [3, 4]. Considering these data, calix
[4]resorcinols containing urea fragments at the
molecule lower rim are of undoubted interest.
Compounds of this type can possess biological activity
and can be used as new synthetic platforms for construc-
tion of the new type supramolecular compounds.
PhNCO + H2N(CH2)3CH(OEt)2
→ PhNHC(O)NH(CH2)3CH(OEt)2.
I
The reaction of acetal I with pyrogallol II was
carried out in the chloroform medium in the presence
of trifluoroacetic acid. As a result, calix[4]resorcinol
III was obtained, composition and structure of which
were confirmed by elemental analysis and spectral
methods.
We have show earlier that a convenient method of
obtaining calix[4]resorcinols is reaction of func-
tionalized acetals with resorcinol and its derivatives
[5]. Aiming at the synthesis of calix[4]resorcinols
OH
OH
HO
OH
OH
HO
4 I + 4
H+
CH
−2 EtOH
(CH2)3
II
NHC(O)NHPh
4
III
Calixarene of the similar composition was also
obtained by other way. Initially we carried out reaction
of 2-methylresorcinol IV with 4,4-diethoxy-1-butyl-
amine V in water–alcohol solution of hydrochloric
acid, resulted in formation of calixarene VI containing
ammonium fragments (Scheme 1).
Treatment of calixarene VI with hexamethyl-
disilazane excess affords calixarene VII containing
free primary amino groups. The latter reacts readily
with phenylisocyanate to form calixarene VIII
involving four urea fragments. Methanolysis of the
crude compound VIII proceeds with desilylation re-
1163

1164
KHAKIMOV et al.
Scheme 1.
Me
OH
HO
Me
OH
HO
H+
4
+ 4 H2N(CH2)3CH(OEt)2
CH
(CH2)3
NH+3
IV
V
Cl−
4
VI
Scheme 2.
Me
Me
OSiMe3
OSiMe3
Me3SiO
Me3SiO
PhNCO
VI + (Me3Si)2NH
CH
CH
(CH2)3
NH2
(CH2)3
NHC(O)NHPh
4
4
VII
VIII
Me
OH
HO
MeOH
CH
(CH2)3
NHC(O)NHPh
4
IX
dimethoxyethyl)-1-methyl-3-phenylurea X, in which
acetal and urea fragments are bound through two
carbon links only. The result was found to be
sufficiently unexpected: the reaction product was
corresponding imidazolidin-2-one XI (Scheme 3).
sulted in calixarene IX, which was isolated and
characterized by elemental analysis, Н NMR and IR
spectroscopy data (Scheme 2).
1
To elucidate influence of urea acetal structure,
including the size of carbon chain binding urea and
acetal fragments, on the synthetic result of reaction, we
studied reaction of pyrogallol II with 1-(2,2-
We supposed that the result obtained is explained
by a possibility of initial monomolecular hetero-
Scheme 3.
OH
11
12
10
OH
HO
Me
14
15
4
CF3COOH
−2 MeOH
9
13
3
16
5
II + PhNHC(O)NCH2CH(OMe)2
N 2
1
8
X
N
6
O
Me
XI
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 6 2009

REACTION OF RESORCINOL AND ITS DERIVATIVES WITH UREA ACETALS
1165
cyclization of acetal X into 1-methyl-3-phenyl-
imidazol-2-one XII followed by reaction of the latter
with pyrogallol. Actually we established by special
experiment that acetal X under the reaction conditions
(in the presence of trifluoroacetic acid) exerts
cyclization into imidazole XII, which reacts with
pyrogallol to form the final product XI (Scheme 4).
(4Н, р-СНAr), 7.18 m (8Н, т-СНAr), 7.27 m (8Н, о-
СНAr). Found, %: C 69.74; H 6.52; N 8.95.
C72H80N8O12. Calculated, %: C 69.21; H 6.45; N 8.97.
4,6,10,12,16,18,22,24-Octahydroxy-5,11,17,23-
tetramethyl-2,8,14,20-tetra(3-ammoniochloridepro-
pyl)pentacyclo[19.3.1.13,7.19,13.115,19]octacoza-1(25),3,5,7-
(28),9,11,13(27),15,17,19(26),21,23-dodecaene (VI).
A mixture of 0.77 g of resorcinol IV, 1.0 g of acetal V,
2.5 ml of concentrated hydrochloric acid, 6 ml of
ethanol and 6 ml of water distilled was heated for 8 h
at 80°С. After the solvent removal the residue was
washed twice with ethanol and dried in vacuum (20°С,
5 mm Hg, 24 h). Yield 1.37 g (24.0%), mp >250°C. IR
Scheme 4.
8
9
5
4
3
CF3COOH
II
Me N1
10
7
XI
X
N
6
2
O
1
spectrum, ν, cm–1: 1600 (СНAr), 3320 (ОН). Н NMR
XII
spectrum (D2O), 20°С, δ, ppm: 1.59 m (8Н, СН2), 1.62
s (12Н, СН3), 2.34 m (8Н, СН2), 3.02 t (8Н, СН2, 3JНН
EXPERIMENTAL
3
7.52 Hz), 4.36 t (4Н, СН, JНН 7.88 Hz), 7.22 s (4Н,
The Н and 13С NMR spectra were registered on a
Bruker AVANCE-600 device (600 and 150 МHz
respectively). The IR spectra were recorded on a UR-
20 device in the range of 400–3600 cm–1 (vaseline oil).
1
СНAr). Found, %: C 57.01; H 6.95; Cl 15.01; N 6.0.
C44H64Cl4N4O8. Calculated, %: C 57.52; H 7.02; Cl
15.43; N 6.10.
4,6,10,12,16,18,22,24-Оctahydroxy-5,11,17,23-
tetramethyl-2,8,14,20-tetra[3-(3-phenylureid)propyl]-
pentacyclo[19.3.1.13,7.19,13.115,19]octacoza-1(25),3,5,7-
(28),9,11,13(27),15, 17,19(26),21,23-dodecaene (IX).
A mixture of 0.45 g of calixarene VI and 5 ml of
hexamethyldisilazane (HMDS) was refluxed for 48 h
to ammoniac release stopping and HMDS excess was
removed under vacuum. The residue was dissolved
into 5 ml of benzene. To this solution 0.23 g of phenyl-
isocyanate was added dropwise and stirred for 14 h at
20°С. Then 5 ml ethanol was added and the reaction
mixture was heated for 3 h at 50°С. After the solvent
removal the residue was reprecipitated from chloro-
form with pentane. Yield 0.22 g (18.4%), mp >250°С.
IR spectrum, ν, cm–1: 1598 (СНAr), 1648 (С=О), 3338
(ОН). 1Н NMR spectrum (CDCl3), 20°С , δ, ppm: 1.34
m (8Н, СН2), 1.51 m (4Н, СН2), 1.95 m (4Н, СН2),
1.72 s (6Н, СН3), 2.09 s (6Н, СН3), 2.79 m (4Н, СН2),
3.35 m (4Н, СН2), 4.31 m (4Н, СН), 6.45 m (4Н,
СНAr), 6.91 m (4Н, р-СНAr), 7.11 m (8Н, т-СНAr),
7.24 m (8Н, о-СНAr). Found, %: C 69.00; H 6.12; N
8.41. C72H80N8O12. Calculated, %: C 69.21; H 6.45; N
8.97.
1-(4,4-Diethoxybutyl)-3-phenylurea (I). To a solu-
tion of 6.0 g of 4,4-diethoxy-1-butylamine in 12 ml of
benzene was added dropwise 4.43 g of phenyl-
isocyanate in 6 ml of benzene under argon atmosphere
at 10–15°С. The reaction mixture was stirred for 1 h at
30°С. Then the solvent was removed and residue was
recrystallized from benzene. Yield 9.2 g (65%), mp
66–68°С. IR spectrum, ν, cm–1: 1580 (СНAr), 1634, 1593
1
(C=O), 3284 (NH). Н NMR spectrum [(CD3)2C=O],
3
20°С , δ, ppm: 1.14 t (6Н, СН3CH2O, JНН 6.97 Hz),
3
1.60 q (4Н, CH2O, JНН 3.67 Hz), 3.23 q (2Н, СН2,
3JНН 5.87 Hz), 3.61 m (2Н, СН2), 3.47 m (2Н, NСН2)
3
4.50 t (1Н, СН, JНН 5.13 Hz), 6.92 m (1Н, p-СНAr),
7.22 m (2Н, m-СНAr), 7.46 m (2Н, о-СНAr), 7.86 s
(1Н, NH). Found, %: С 64.07; Н 8.82, N 10.18.
C15H24N2O3. Calculated, %: C 64.26; H 8.63; N 9.99.
4,5,6,10,11,12,16,17,18,22,23,24-Dodecahydroxy-
2,8,14,20-tetra[3-(3-phenylureido)propyl]penta-
cyclo[19.3.1.13,7.19,13.115,19]octacoza-1(25),3,5,7(28),9,11,-
13(27),15,17,19(26),21,23-dodecaene (III). A mixture
of 0.3 g of acetal I, 0.14 g of pirogallol, 0.1 ml of
trifluoroacetic acid and 3 ml of chloroform was heated
for 25 h at 60°С. After the solvent removal the residue
was reprecipitated from chloroform with pentane as a
grey powder. Yield 0.25 g (64%), mp >250°C. IR
spectrum, ν, cm–1: 1608 (СНAr), 1653 (С=О), 3330
1-(2,2-Dimethoxyethyl)-1-methyl-3-phenylurea (X).
A solution of 3.0 g of 2,2-dimethoxyethylmethylamine
and 3.0 g of phenylisocyanate in 9 ml of benzene was
heated for 1 h at 30°С. After the solvent removal the
residue was recrystallized from benzene. Yield 3.9 g
(65%), mp 66–68°С . IR spectrum, ν, cm–1: 1461, 1580
1
(ОН). Н NMR spectrum (CD3OD), 20°С , δ, ppm:
1.48 m (8Н, СН2), 1.98 m (8Н, СН2), 3.18 m (8Н,
СН2), 4.42 m (4Н, СН), 6.37 m (4Н, СНAr), 6.93 m
1
(СНAr), 1634 (C=O), 3284 (NH). Н NMR spectrum
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 6 2009

1166
KHAKIMOV et al.
(CDCl3), δ, ppm: 3.04 s (3Н, СН3N), 3.41 s (6Н,
9.66 Hz, 3JНН 7.05 Hz), 6.41 d (1Н, НС9, 3JНН 8.36 Hz),
6.51 d (1Н, НС8, 3JНН 8.36 Hz), 6.97 t (1Н, НС16, 3JНН
7.31 Hz), 7.25 t (2Н, НС15, 3JНН 8.09 Hz), 7.48 d (2Н,
3
СН3О), 3.43 d (2Н, СН2, JНН 5.30 Hz), 4.55 t (1Н,
3
СН, JНН 5.30 Hz), 7.22 m (5Н, С6Н5). Found, %: С
3
13
60.07; Н 7.82, N 11.58. C12H18N2O3. Calculated, %: C
60.49; H 7.61; N 11.76.
НС14, JНН 7.84 Hz). C NMR spectrum (CD3OD), δ,
1
1
ppm: 29.57 (С6, JСН 137.84 Hz), 51.86 (С4, JСН
145.95 Hz), 55.39 (С5, JСН 145.40 Hz), 108.34 (С9,
1
1-Methyl-3-phenylimidazol-2-one (XII). A mix-
ture of 4.0 g of urea X, 2.1 g of trifluoroacetic acid and
25 ml of chloroform was heated for 4 h at 60°С. After
the solvent removal the residue was washed with
diethyl ether. Yield 2.45 g (90.8%), mp 117°С. IR
spectrum, ν, cm–1: 1595 (СНAr), 1642 (С=С), 1679
1JСН 161.43 Hz), 118.40 (С14, JСН 158.66 Hz), 118.49
1
1
1
(С7), 119.29 (С15, JСН 159.22 Hz), 123.70 (С16, JСН
160.32 Hz), 129.84 (С8, JСН 158.66 Hz), 141.85 (С13),
1
134.49 (С11), 147.23, 146.18 (С10, С12), 160.30 (С2).
Found, %: C 63.56; H 5.25; N 9.53. С6H16N2O4.
Calculated, %: C 63.99; H 5.37; N 9.33.
1
(С=О). Н NMR spectrum (CDCl3), 20°С, δ, ppm:
3.28 s (3H, HC6), 6.29 d (1Н, НС4, 3JНН 2.93 Hz), 6.54
ACKNOWLEDGMENTS
3
3
d (1Н, НС5, JНН 2.93 Hz), 7.21 t (1Н, НС10, JНН
7.33 Hz), 7.38 t (2Н, НС9, 3JНН 7.92 Hz), 7.59 d (2Н,
НС8, 3J 8.21 Hz). Found, %: C 68.43; H 6.21; N 16.54.
C10H10N2O. Calculated, %: C. 68.95; H 5.79; N 16.08.
This work was financially supported by the Russian
Foundation for Basic Research (grant no. 08-03-
00512).
3-Methyl-1-phenyl-4-(2,3,4-trihydroxyphenyl)-
imidazolydin-2-one (XI). To a mixture of 1.6 g of
pyrogallole, 1.58 g of trifluoroacetic acid and 25 ml of
chloroform was slowly added dropwise a solution of
3.0 g of urea X in 15 ml of chloroform. The reaction
mixture was heated for 8 h at 60°С. After the solvent
removal the residue was dissolved into 3 ml of
chloroform and kept overnight. The precipitate was
filtered off and washed with 50 ml of diethyl ether.
Yield 2.93 g (80.7%), mp 150–151°С. IR spectrum, ν,
REFERENCES
1. Budka, J., Lhotak, P., Michlova, V., and Stibor, I.,
Tetrahedron Lett., 2001, vol. 42, p. 1583.
2. Mogck, O., Bohmer, V., and Vogt, W., Tetrahedron,
1996, vol. 52, no. 25, p. 8489.
3. Oi, N., Kitahara, H., Aoki, F., and Kisu, N., J. Chrom.
A., 1995, vol. 689, p. 195.
4. Oi, N., Kitahara, H., and Aoki, F., J. Chrom. A., 1995,
vol. 694, p. 129.
1
cm–1: 1600 (СНAr), 1692, 1653 (С=О), 3337 (ОН). Н
5. Burilov, A.R., Volodina, Yu.М., Popova, E.V., Gazi-
zov, A.S., Knyazeva, I.R., Pudovik, М.А., Khabi-
kher, V.D., and Konovalov, А.I., Zh. Obshch. Khim.,
2006, vol. 76, no. 3, p. 433.
NMR spectrum (CD3OD), δ, ppm: 2.67 s (3Н, НС6),
3
3.61 d. d (1Н, НС4, 2JНН 8.88 Hz, J 6.79 Hz), 4.07 t
3
2
(1Н, НС5, JНН 9.40 Hz), 4.87 d. d (1H, НС4, JНН
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 79 No. 6 2009