Synthesis of 1-(oxiran-2-ylmethyl)-1H-indole-3-carbaldehyde and its reaction with active methylene compounds

Article abstract of DOI:10.1007/s10593-011-0878-x

Treatment of indole-3-carbaldehyde with epichlorohydrin gave 1-(oxiran-2-ylmethyl)-1H-indole-3-carb-aldehyde, reaction of which with 1,3-dimethylbarbituric acid or malononitrile gave crotonic condensation products with retention of the oxirane ring. The s

Full text of DOI:10.1007/s10593-011-0878-x

Chemistry of Heterocyclic Compounds, Vol. 47, No. 9, December, 2011 (Russian Original Vol. 47, No. 9, September, 2011)
SYNTHESIS OF 1-(OXIRAN-2-YLMETHYL)-1H-INDOLE-
3-CARBALDEHYDE AND ITS REACTION WITH ACTIVE
METHYLENE COMPOUNDS
K. F. Suzdalev1 and S. V. Den'kina1*
Treatment of indole-3-carbaldehyde with epichlorohydrin gave 1-(oxiran-2-ylmethyl)-1H-indole-3-carb-
aldehyde, reaction of which with 1,3-dimethylbarbituric acid or malononitrile gave crotonic
condensation products with retention of the oxirane ring. The structure of the reaction products with
aroylglycines depends on the conditions. In acetic anhydride a simultaneous formation of an oxazolone
ring and bisacylation of the oxirane fragment occurs; the use of ethyl chloroformate in the presence of
triethylamine allows to carry out only the heterocyclization process. When treated with the cyclic
amines (N-methylpiperazine or morpholine) opening of the oxazolone ring in the products occurs with
formation of the corresponding amides.
Keywords: amide, indolylmethyleneoxazolone, 1-(oxiran-2-ylmethyl)-1H-indole-3-carbaldehyde, crotonic
condensation, oxazolone ring opening.
1-(Oxiran-2-ylmethyl)-1H-indoles [1] are convenient starting materials for the synthesis of a series of
compounds with promising practical uses. The amino alcohol hydrochlorides, obtained by alkylation of 3-ethoxy-
carbonyl-5-methoxyindoles using epichlorohydrin and subsequent opening of the oxirane ring in the presence of
amines, show high neurotropic activity approaching that of imipramine and capable of increasing the
pharmacological activity of the medicine Levodopa [2]. Publication [3] reports the synthesis of amino alcohols
containing an unsaturated ketone residue at the position 3 of an indole ring. 1-(Oxiran-2-ylmethyl)-1H-indoles and
carbazoles have been used in the preparation of compounds with photosemiconductor properties [4].
The presence of a carbonyl group and an oxiranylmethyl group simultaneously in the indole molecule
increases its synthetic potential due to the presence of two, nonequivalent reaction centers [5]. The aldehyde
group can be used in the preparation of crotonic condensation products. In this respect the reaction with
aroylglycines is of particular interest because it gives indolyl methyleneoxazolones which are reagents used in
the synthesis of amino acid derivatives [6].
_______
*To whom correspondence should be addressed, e-mail: sofia1984@inbox.ru.
1Institute of Physical and Organic Chemistry, Southern Federal University, 194/2 Stachka Ave., Rostov-on Don
344090, Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1321-1327, September, 2011.
Original article submitted November 10, 2010. Revision submitted March 1, 2011.
0009-3122/11/4709-1085©2011 Springer Science+Business Media, Inc.
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4-Hydroxy-1-(oxiran-2-ylmethyl)-1H-indole-3-carbaldehyde was prepared in 44% yield together with
1-(3-chloro-2-hydroxypropyl)-1H-indole-3-carbaldehyde (42%) by treating 4-hydroxy-1H-indole-3-carbalde-
hyde with epichlorohydrin in the presence of sodium ethylate [7]. The analogous 1-(1-methyl-1-oxiranylethyl)-
1H-indole-3-carbaldehyde has been reported as an intermediate product in the synthesis of the natural cyclic
peptide cyclomarin A [8].
In this publication we report the synthesis of the simplest representative of this class of compound, i.e.
the 1-(oxiran-2-ylmethyl)-1H-indole-3-carbaldehyde (2) and its reactions with active methylene compounds.
Treatment of the indole-3-carbaldehyde (1) with epichlorohydrin in the presence of sodium hydroxide gives the
expected epoxide 2 and the compound 3 having two indole fragments. Formation of the latter is a result of the
oxirane ring opening in compound 2 induced by the N-indolyl anion present in the reaction mixture.
O
O
O
O
O
Cl
N
N
+
OH
NaOH, DMSO
N
N
H
O
1
2
3
1
In the H NMR spectrum signals for the OCH2 group protons of the oxirane fragment of product 2 are
nonequivalent due to the presence of an asymmetric carbon atom. The multiplet signal for the proton on the
chiral carbon atom is in the range of 3.29-3.40 ppm. The signals for the NCH2 group protons are observed as a
1
doublet of doublets at 4.15 and 4.56 ppm. In the H NMR spectrum of compound 3 the signal for the hydroxyl
group appears as a doublet at 5.58 ppm, disappearing upon deuteration.
Reaction of aldehyde 2 with the active methylene compounds (1,3-dimethylbarbituric acid and malono-
nitrile) gives the condensation products 4 and 5 respectively.
On an attempt to synthesize the oxazolone by a classical Erlenmeyer-Plöchl reaction (heating the indole-
3-carbaldehyde 2 with hippuric acid in acetic anhydride) both the formation of the oxazolone ring and
bisacylation of the epoxy fragment occurred. This was indicated by the appearance of two methyl groups
1
singlets at 2.02 and 2.12 ppm in the H NMR spectrum of the product 6. The oxazolones 7a,b (retaining the
oxiranylmethyl group at position 1 of the indole fragment) were prepared by a modified Erlenmeyer-Plöchl
reaction in which the starting aldehyde 2 reacted with aroylglycines and ethyl chloroformate in the presence of
triethylamine [9].
It is known that in the reaction of indolylmethylene isoxazoles of type 6 and 7a,b with amines 2-amino-
3-indolylacrylic acid amides can be obtained [10]. They include in their structure an amino group separated by
two carbon atoms from the indole bicycle. Such a structure is a characteristic for many biologically active
natural indoles, viz. the amino acid tryptophan, the neurotransmitter serotonin, and -carboline series alkaloids
[11]. We have previously shown that several 2-amino-3-indolylacrylic acid amides possess local anesthetic and
anti-arrhythmic activity [12]. With the aim to synthesize analogous substances containing an oxirane ring in
addition to a tryptophan fragment, we have treated the oxazolones 6 and 7a,b with amines.
Compounds 6 and 7a,b were reacted with cyclic amines (N-methylpiperazine or morpholine) to give the
amides 8 and 9a-d respectively as the products of an oxazolone ring opening. Compounds 9a-d were obtained
when the reaction was carried out at room temperature but heating in benzene led to the formation of a mixture
of unidentified products.
Hence examples presented show that on the basis of 1-(oxiran-2-ylmethyl)-1H-indole-3-carbaldehyde (2),
heterocyclic indole derivatives having an oxiran-2-ylmethyl fragment on the nitrogen atom can be obtained.
1086

O
O
Me
Me
Me
O
N
N
CN
CN
N
O
O
CH2(CN)2,
Et3N
N
Me
O
2
BuOH
2-PrOH
N
N
Hippuric
Aroylglycines
acid
O
ClCO2Et
Et3N
Ac2O
O
5
O
O
4
O
O
Ph
N
N
R
N
N
AcO
AcO
O
X
7a,b
Et3N
6
HN
PhH
HN
N Me
PhH
O
O
N
N Me
N
X
NH
NH
Ph
O
O
N
R
N
AcO
AcO
9a–d
O
8
7a R = H, b R = Me; 9a,b R = H, c,d R = Me; 9a,c X = O, b,d X = NMe
EXPERIMENTAL
IR spectra were recorded on a Varian 3100 FT-IR Excalibur Series instrument by the attenuated total
1
reflectance method using a zinc selenide crystal. H and 13C NMR spectra were taken on a Bruker DPX-250
spectrometer (250 and 60 MHz respectively) using CDCl3 (compounds 2, 4-9) and DMSO-d6 (compound 3)
with the residual protons of the deuterated solvent as internal standard. Mass spectra (EI, 70 eV) were obtained
on a Varian MAT-44 spectrometer.
N-(p-Methylbenzoyl)glycine was prepared by method [13] and the indole-3-carbaldehyde (1) by
method [14].
1-(Oxiran-2-ylmethyl)-1H-indole-3-carbaldehyde (2) and 1,1'-(2-Hydroxypropane-1,3-diyl)bis-
(1H-indole-3-carbaldehyde) (3). NaOH (9.2 g, 230 mmol) in water (10 ml) was added to the aldehyde 1 (30 g,
200 mmol) in DMSO (40 ml) and the mixture was stirred for 1-1.5 h at room temperature. Epichlorohydrin
(47 ml, 600 mmol) was added to the solution obtained and the product was left for 1 h at room temperature and
then slowly heated to 60ºC. The warm mixture was poured into water (300 ml) and extracted with benzene
(350 ml). The precipitate of the product 3 formed by cooling the aqueous layer was filtered off and
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recrystallized from n-butanol. The benzene extract was dried over Na2SO4, evaporated to a volume of 10-15 ml,
and passed through an alumina column (alumina layer thickness 30 cm, diameter 4 cm, eluent benzene). The
filtrate was evaporated and the residue was recrystallized from benzene to give compound 2 (10 g, 25%); mp
90-92ºC. IR spectrum, , cm-1: 1528, 1574, 1611 (C–C arom.), 1646 (C=O). 1H NMR spectrum, , ppm (J, Hz):
2.46-2.53 (1H, m) and 2.80-2.93 (1H, m, OCH2); 3.29-3.40 (1H, m, OCH); 4.15 (1H, dd, 2J = 15.6, 3J = 5.2) and
2
3
4.56 (1H, dd, J = 15.6, J = 3.3, NCH2); 7.26-7.48 (3H, m, H-5,6,7); 7.76 (1H, s, H-2); 8.29-8.38 (1H, m,
H-4); 10.00 (1H, s, CH=O). 13C NMR spectrum, , ppm: 45.5; 48.9; 50.6; 110.3; 119.1; 122.6; 123.5; 124.7;
125.6; 137.9; 139.3; 185.1. Found, %: C 71.34; H 5.49; N 6.93. C12H11NO2. Calculated, %: C 71.63; H 5.51;
N 6.96.
Compound 3. Yield 4 g (12%); mp 222-225ºC. IR spectrum, , cm-1: 1609 (C–C arom.), 1643 (C=O),
1
3426 (OH). H NMR spectrum, , ppm (J, Hz): 4.15-4.30 (3H, m, NCH2, CH); 4.50-4.65 (2H, m, NCH2); 5.58
(1H, d, J = 4.4, OH); 7.20-8.33 (10H, m, H Ar); 9.91 (2H, s, CH=O). 13C NMR spectrum, , ppm: 51.2 (2C);
69.0 (1C); 112.2 (2C); 118.1 (2C); 121.9 (2C); 123.3 (2C); 124.3 (2C); 125.6 (2C); 138.4 (2C); 142.7 (2C);
185.6 (2C). Mass spectrum, m/z (Irel, %): 346 [M]+ (6.6). Found, %: C 72.53; H 5.22; N 8.06. C21H18N2O3.
Calculated, %: C 72.82; H 5.24; N 8.09.
1,3-Dimethyl-5-{[1-(oxiran-2-ylmethyl)-1H-indol-3-yl]methylidene}pyrimidine-2,4,6(1H,3H,5H)-
trione (4). 1,3-Dimethylbarbituric acid (310 mg, 2 mmol) was added to compound 2 (402 mg, 2 mmol) in
n-butanol (7 ml). The reaction product was refluxed for 1 h. After cooling, the yellow precipitate formed was
filtered off and recrystallized from acetonitrile to give compound 4 (410 mg, 61%); mp 220-224ºC. IR spectrum,
, cm-1: 1499, 1581 (C–C arom.), 1650, 1716 (C=O). 1H NMR spectrum, , ppm (J, Hz): 2.53-2.69 (1H, m) and
2
3
2.86-3.01 (1H, m, OCH2); 3.33-3.60 (7H, m, 2CH3, OCH); 4.29 (1H, dd, J = 15.2, J = 5.7) and 4.68 (1H, dd,
2J = 15.2, 3J = 2.7, NCH2); 7.16-7.58 (3H, m, H-5,6,7); 7.85-8.02 (1H, m, H-4); 8.90 (1H, s, H-2); 9.53 (1H, s,
CH=O). 13C NMR spectrum, , ppm: 28.5; 29.2; 45.7; 50.0; 50.6; 109.3; 111.3; 112.8; 119.2; 123.8; 124.7;
130.8; 137.4; 142.7; 146.5; 152.1; 162.5; 164.1. Found, %; C 63.46; H 5.03; N 12.33. C18H17N3O4. Calculated,
%: C 63.71; H 5.05; N 12.38.
{[1-(Oxiran-2-ylmethyl)-1H-indol-3-yl]methylidene}malononitrile (5). Malononitrile (100 mg,
1.5 mmol) and triethylamine (0.1 ml, 1 mmol) were added to compound 2 (201 mg, 1 mmol) in 2-propanol
(2 ml). The product was heated to reflux for 1-2 min. The yellow precipitate formed on cooling was filtered off
and recrystallized from 2-propanol to give compound 5 (110 mg, 44%); mp 158-160ºC. IR spectrum, , cm-1:
1574, 1587, 1616 (C–C arom.), 2211 (CN). 1H NMR spectrum, , ppm (J, Hz): 2.50-2.58 (1H, m) and 2.86-2.92
(1H, m, OCH2); 3.29-3.37 (1H, m OCH); 4.19 (1H, dd, 2J = 15.2, 3J = 6.0) and 4.62 (1H, dd, 2J = 15.2, 3J = 2.6,
NCH2); 7.32-7.76 (4H, m, H-4,5,6,7); 8.03 (1H, s, H-2); 8.46 (1H, s, CH=). 13C NMR spectrum, , ppm: 45.8;
50.0; 50.5; 70.4; 111.3; 111.5; 115.8 (2C); 118.7; 124.0; 125.3; 128.0; 135.0; 137.0; 150.4. Found, %: C 71.99;
H 4.43; N 16.79. C15H11N3O. Calculated, %: C 72.28; H 4.45; H 16.86.
3-{3-[(5-Oxo-2-phenyl-1,3-oxazol-4(5H)-ylidene)methyl]-1H-indol-1-yl}propane-1,2-diyl
Diacetate
(6). Hippuric acid (1.43 g, 8 mmol) was added to compound 2 (1.61 g, 8 mmol) in acetic anhydride (3 ml). The
mixture was held for 3 h at 120-135ºC. The cooled reaction product was poured into water (100 ml) and the
precipitate formed was filtered off, dried, dissolved in dichloromethane, and passed through an alumina column
(thickness 30 cm, diameter 4 cm, eluent dichloromethane). Solvent was distilled off on a water bath and diethyl
ether (5 ml) was added to the oily residue. The solid formed was filtered off and recrystallized from benzene to
give compound 6 (360 mg, 10%); mp 165-168ºC. IR spectrum, , cm-1: 1644 (C–C arom.), 1747, 1777 (C=O).
1H NMR spectrum, , ppm (J, Hz): 2.02 (3H, s CH3); 2.12 (3H, s, CH3); 4.05-4.18 (1H, dd, 2J = 12.3, 3J = 4.9)
2
3
and 4.25-4.35 (1H, dd, J = 12.1, J = 4.4, NCH2); 4.40-4.52 (2H, m, CH2OAc); 5.35-5.50 (1H, m, CHOAc);
7.20-8.20 (10H, m, H Ar). 8.46 (1H, s, CH=). 13C NMR spectrum, , ppm: 21.2 (2C); 47.1; 62.8; 70.1; 110.4;
112.8; 120.0; 122.8; 124.3; 125.0; 126.6; 128.2 (2C); 128.3; 129.1; 129.3 (2C); 133.0; 136.3; 137.2; 161.2;
168.1; 170.3; 170.7. Found, %: C 66.99; H 4.95; N 6.24. C25H22N2O6. Calculated, %: C 67.26; H 4.97; N 6.27.
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4-{[1-(Oxiran-2-ylmethyl)-1H-indol-3-yl]methylidene}-2-phenyl-1,3-oxazol-5(4H)-one (7a) and
2-(p-Methylphenyl)-4-{[1-(oxiran-2-ylmethyl)-1H-indol-3-yl]methylidene}-1,3-oxazol-5(4H)-one (7b)
(General Method). Triethylamine (11.3 ml, 81 mmol) was added to the aroylglycine (47 mmol) in absolute
benzene (45 ml). After 40 min, ethyl chloroformate (5.6 ml, 59 mmol) was added dropwise. The precipitated
triethylamine hydrochloride was filtered off and washed with benzene and compound 2 (9.4 g, 47 mmol) was
added to the combined filtrate. The reaction product was refluxed for 3-4 h. Solvent was distilled off on a rotary
evaporator to a volume of 10-15 ml. The precipitate formed on cooling this material was filtered off and
recrystallized from 2-propanol.
Compound 7a. Yield 5.2 g (32%); mp 174-184ºC. IR spectrum, , cm-1: 1597, 1637 (C–C arom), 1758,
1
1777 (C=O). H NMR spectrum, , ppm (J, Hz): 2.53-2.61 (1H, m) and 2.84-2.92 (1H, m, OCH2); 3.33-3.43
2
3
2
3
(1H, m, OCH); 4.27 (1H, dd, J = 15.2, J = 5.4) and 4.61 (1H, dd, J = 15.2, J = 2.8, NCH2); 7.28-8.19
(10H, m, H Ar); 8.51 (1H, s, CH=). 13C NMR spectrum, , ppm: 45.6; 49.2; 50.9; 110.8; 112.4; 119.9; 122.7;
124.1; 125.2; 126.6; 128.2 (2C); 128.3; 128.8; 129.3 (2C); 132.9; 136.5; 137.3; 161.0; 168.2. Found, %:
C 73.22; H 4.66; N 8.09. C21H16N2O3. Calculated, %: C 73.24; H 4.68; N 8.13.
Compound 7b. Yield 6.2 g (37%); mp 165-168ºC. IR spectrum, , cm-1: 1511, 1553, 1578, 1642 (C–C
1
arom.), 1760, 1776 (C=O). H NMR spectrum, , ppm (J, Hz): 2.44 (3H, s, CH3); 2.53-2.60 (1H, m) and
2
3
2.85-2.91 (1H, m, OCH2); 3.34-3.42 (1H, m, OCH); 4.29 (1H, dd, J = 15.2, J = 5.7) and 4.59 (1H, dd,
2J = 15.2, 3J = 3.2, NCH2); 7.25-8.08 (9H, m, H Ar); 8.50 (1H, s, CH=). 13C NMR spectrum, , ppm: 22.2; 45.6;
49.2; 50.9; 110.8; 112.4; 119.8; 122.5; 123.8; 124.0; 124.5; 128.2 (2C); 128.3; 128.9; 130.0 (2C); 136.3; 137.2;
143.7; 161.1; 168.3. Found, %: C 73.44; H 5.04; N 7.79. C22H18N2O3. Calculated, %: C 73.73; H 5.06; N 7.82.
3-{3-[2-(Benzoylamino)-3-(4-methylpiperazin-1-yl)-3-oxoprop-1-en-1-yl]-1H-indol-1-yl}propane-
1,2-diyl Acetate (8). N-Methylpiperazine (0.17 g, 1.5 mmol) was added to compound 6 (450 mg, 1 mmol) in
benzene (3 ml). The reaction mixture was refluxed for 20-30 min until the yellow color disappeared. The white
precipitate formed on cooling was filtered off and recrystallized from benzene to give compound 8 (350 mg,
67%); mp 173-176ºC. IR spectrum, , cm-1: 1532, 1605 (C–C arom.), 1650, 1743 (C=O), 3263 (NH). 1H NMR
spectrum, , ppm (J, Hz): 1.85 (3H, s, CH3); 1.95 (3H, s, CH3); 2.30 (3H, s, NCH3); 2.36-2.48 (4H, m, N(CH2)2
piperazine); 3.59-3.86 (4H, m, N(CH2)2 piperazine); 3.96-4.07 (1H, m) and 4.17-4.41 (3H, m, NCH2, CH2OAc);
5.23-5.37 (1H, m, CHOAc); 6.41 (1H, s, CH=); 7.15-7.95 (10H, m, H Ar); 8.51 (1H, s, NH). 13C NMR
spectrum, , ppm: 20.9; 21.1; 46.4; 46.5; 54.9 (4C); 62.3; 70.3; 110.2; 110.3; 115.8; 119.3; 121.2; 123.5; 126.7;
127.9; 128.2 (2C); 128.8 (2C); 129.1; 132.2; 133.2; 136.7; 166.5; 168.8; 170.4; 170.6. Found, %: C 65.66;
H 6.25; N 10.21. C30H34N4O6. Calculated, %: C 65.92; H 6.27; N 10.25.
N-[1-(Morpholin-4ylcarbonyl)- (9a), N-[1-(4-Methylpiperazin-1-ylcarbonyl)- (9b), 4-Methyl-
N-[1-(morpholin-4-ylcarbonyl)- (9c), and 4-Methyl-N-{1-[(4-methylpiperazin-1-yl)carbonyl]- (9d)
2-[1-(oxiran-2-ylmethyl)-1H-indol-3-yl]vinyl Benzamide (General Method). Compound 7 (1 mmol) and
triethylamine (0.1 ml, 1 mmol) were added to N-methylpiperazine or morpholine (1.5 mmol) in benzene (3 ml).
After the color of the solution had disappeared, diethyl ether was added in small portions. The white precipitate
of compound 9 was filtered off and recrystallized from benzene.
Compound 9a. Yield 36%; mp 135-136ºC. IR spectrum, , cm-1: 1603 (C–C arom.), 1649 (C=O), 3260
1
(NH). H NMR spectrum, , ppm (J, Hz): 2.40-2.46 (1H, m) and 2.74-2.82 (1H, m, OCH2); 3.22-3.30 (1H, m,
OCH); 3.59-3.77 (8H, m, 2(CH2)2 morpholine); 4.13 (1H dd, 2J = 15.1, 3J = 5.6) and 4.47 (1H, dd, 2J = 15.1,
3J = 2.8, NCH2); 6.39 (1H, s, CH=); 7.15-7.94 (10H, m, H Ar); 8.60 (1H, s, NH). 13C NMR spectrum, , ppm:
45.5; 48.5; 51.1; 66.9 (4C); 109.8; 110.4; 115.8; 119.2; 121.1; 123.5; 126.2; 127.8; 128.2 (2C); 128.8 (2C);
129.2; 132.2; 133.1; 136.7; 166.5; 169.2. Mass spectrum, m/z (Irel, %): 431 [M]+ (0.8). Found, %: C 69.31;
H 5.82; N 9.70. C25H25N3O4. Calculated, %: C 69.59; H 5.84; N 9.74.
Compound 9b. Yield 51%; mp 172-176ºC. IR spectrum, , cm-1: 1532, 1602, 1603 (C–C arom.), 1650
1
(C=O), 3249 (NH). H NMR spectrum, , ppm (J, Hz): 2.31 (3H, s, CH3); 2.38-2.50 (5H, m, OCH2, N(CH2)2
piperazine); 2.75-2.82 (1H, m, OCH2); 3.21-3.32 (1H, m, OCH); 3.66-3.86 (4H, m, N(CH2)2 piperazine); 4.14
(1H, dd, 2J = 15.3, 3J = 5.5) and 4.49 (1H, dd, 2J = 15.3, 3J = 2.6, NCH2); 6.43 (1H, s, CH=); 7.13-7.95 (10H,
1089

m, H Ar); 8.31 (1H, s, NH). 13C NMR spectrum,, ppm: 45.6; 46.4; 48.6; 51.1; 55.0 (4C); 110.0; 110.4; 115.9;
119.2; 121.1; 123.4; 126.4; 128.0; 128.2 (2C); 128.8 (2C); 129.2; 132.1; 133.3; 136.7; 166.5; 168.9. Found, %:
C 69.97; H 6.32; N 12.55. C26H28N4O3. Calculated, %: C 70.25; H 6.35; N 12.60.
Compound 9c. Yield 34%; mp 151-154ºC. IR spectrum, , cm-1: 1470, 1528, 1606 (C–C arom.); 1647
(C=O); 3250 (NH). 1H NMR spectrum, , ppm (J, Hz): 2.35 (3H, s, CH3); 2.39-2.45 (1H, m) and 2.74-2.83 (1H,
2
3
m, OCH2); 3.21-3.31 (1H, m, OCH); 3.55-3.85 (8H, m, 2(CH2)2 morpholine); 4.14 (1H, dd, J = 15.3, J = 5.5)
2
3
and 4.47 (1H, dd, J = 15.3, J = 2.7, NCH2); 6.37 (1H, s, CH=); 7.06-7.86 (9H, m, H Ar); 8.42 (1H, s, NH).
13C NMR spectrum, , ppm: 21.8; 45.5; 48.5; 51.1; 66.9 (4C); 109.9; 110.3; 115.0; 119.3; 121.1; 123.4; 126.6;
127.8; 128.1 (2C); 129.0; 129.5 (2C); 130.4; 136.7; 142.7; 166.3; 169.1. Found, %: C 69.82; H 6.09; N 9.39.
C26H27N3O4. Calculated, %: C 70.10; H 6.11; N 9.43.
Compound 9d. Yield 32%; mp 182-184ºC. IR spectrum, , cm-1: 1470, 1530, 1603 (C–C arom.), 1648
(C=O), 3267 (NH). 1H NMR spectrum, , ppm (J, Hz): 2.32 (3H, s, CH3); 2.37 (3H, s, CH3); 2.37-2.49 (5H, m,
OCH2, N(CH2)2 piperazine); 2.75-2.82 (1H, m, OCH2); 3.21-3.31 (1H, m, OCH); 3.60-3.86 (4H, m, N(CH2)2
2
3
2
piperazine); 4.15 (1H, dd, J = 15.2, J = 5.4) and 4.47 (1H, dd, J = 15.2, 3J = 2.8, NCH2); 6.39 (1H, s, CH=);
7.10-7.83 (9H, m, H Ar); 8.03 (1H, s, NH). 13C NMR spectrum, , ppm: 21.8; 45.5; 46.4; 48.5; 51.1; 55.0 (4C);
110.0; 110.3; 114.8; 119.4; 121.1; 123.4; 126.8; 127.8; 128.1 (2C); 128.9; 129.5 (2C); 130.6; 136.7; 142.6;
166.1; 168.6. Found, %: C 70.44; H 6.56; N 12.17. Calculated, %: C 70.72; H 6.59; N 12.22.
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