Reduction of 3-carbonyl-substituted 5,6-dicyanobenzofurans with sodium borohydride

Article abstract of DOI:10.1007/s11172-011-0256-y

Reduction of 3-R-carbonyl-substituted 5,6-dicyanobenzofurans with sodium borohydride was studied under various conditions. 3-R-Carbonyl-substituted 5,6-dicyanobenzofurans are selectively reduced in ethanol to substituted 3-R-(hydroxymethyl)-5,6-dicyano-2-

Full text of DOI:10.1007/s11172-011-0256-y

Russian Chemical Bulletin, International Edition, Vol. 60, No. 8, pp. 1719—1722, August, 2011
1719
Reduction of 3ꢀcarbonylꢀsubstituted 5,6ꢀdicyanobenzofurans
with sodium borohydride
Zh. V. Chirkova,a S. I. Filimonov,a I. G. Abramov,a S. I. Firgang,b and G. A. Stashinab
aYaroslavl State Technical University,
88 Moskovskii prosp., 150023 Yaroslavl, Russian Federation.
Fax: +7 (485) 244 0729. Eꢀmail: filimonovsi@ystu.ru
bN. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (499) 135 5328
Reduction of 3ꢀRꢀcarbonylꢀsubstituted 5,6ꢀdicyanobenzofurans with sodium borohydride
was studied under various conditions. 3ꢀRꢀCarbonylꢀsubstituted 5,6ꢀdicyanobenzofurans are
selectively reduced in ethanol to substituted 3ꢀRꢀ(hydroxymethyl)ꢀ5,6ꢀdicyanoꢀ2ꢀmethylbenzoꢀ
furans, products of more deep reduction, viz., substituted 3ꢀRꢀ(hydroxymethyl)ꢀ2ꢀmethylꢀ
2,3ꢀdihydroꢀ5,6ꢀdicyanobenzofurans, 3ꢀRꢀ(hydroxymethyl)ꢀ5,6ꢀdicyanoꢀ2ꢀmethylbenzoꢀ
furans, and 3ꢀalkylꢀsubstituted 4ꢀhydroxyphthalonitriles, are formed in tetrahydrofuran.
Key words: 3ꢀRꢀcarbonylꢀsubstituted 5,6ꢀdicyanobenzofurans, sodium borohydride, carboꢀ
nyl group, 3ꢀRꢀ(hydroxymethyl)ꢀ5,6ꢀdicyanoꢀ2ꢀmethylbenzofurans, 3ꢀRꢀ(hydroxymethyl)ꢀ5,6ꢀ
1
dicyanoꢀ2ꢀmethylꢀ2,3ꢀdihydrobenzofurans, stereoꢀ and regioselective reduction, Hꢀ1Hꢀcorꢀ
relation NOESY spectroscopy.
Pharmaceutical drugs of benzofuran series containing
a keto group at position 3 are well known. Such medicines
as Amiodarone, the third class antiarrhythmic, Benzbromꢀ
arone and Benziodarone, medicines assisting in liberation
of uric acid,1 Вenzofurocainum, the local anaesthetic,2
Cloridarol, a vasodilator, whose carbonyl group at posiꢀ
tion 3 is substituted for the hydroxy one. Application of
compounds of dihydrobenzofuran series in practical medꢀ
icine is also described.1 All this confirm actuality of the
studies directed on the development of methods for the
synthesis of new compounds of benzofuran series by the
selective reduction of the carbonyl group.
We studied reduction of 3ꢀRꢀcarbonylꢀsubstituted
5,6ꢀdicyanoꢀ2ꢀmethylbenzofurans11 1a—e with NaBH4 in
EtOH and THF. It was found that the reduction of benzoꢀ
furans 1a—d in EtOH with a twoꢀfold excess of NaBH4
(20—25 °C, 30 min) leads to 3ꢀRꢀ(hydroxymethyl)ꢀ5,6ꢀdiꢀ
cyanoꢀ2ꢀmethylbenzofurans 2a—d in high yield (60—75%).
Reduction of benzofurans 1a—d in THF (20—25 °C, 2 h)
is nonselective and leads to the mixtures of products with
different extent of reduction: 3ꢀRꢀ(hydroxymethyl)ꢀ5,6ꢀdiꢀ
cyanoꢀ2ꢀmethylbenzofurans 2a—d (40—60%), 3ꢀRꢀ(hydrꢀ
oxymethyl)ꢀ5,6ꢀdicyanoꢀ2ꢀmethylꢀ2,3ꢀdihydrobenzoꢀ
furans 3b—d (20—40%), and 4ꢀhydroxyꢀ5ꢀ{1ꢀ[hydroxyꢀ
(4ꢀR)methyl]propyl}phthalonitriles 4b—d (Scheme 1).
Compound 1a was an exception, since no products of its
deep reduction were isolated. In the case of compound 1d,
the reduction product 3d was obtained in low yield (18%),
whereas the corresponding phenol compound 4d was deꢀ
tected in trace amounts.
It was found that treatment of benzofuran 1e with
NaBH4 in EtOH and in THF does not lead to the reducꢀ
tion of the ester group to form the corresponding aliphatic
alcohol.9 Reduction in ethanol results in the benzofuran
ring opening and leads to a mixture of E/Zꢀisomers of
ethyl 2ꢀ(4,5ꢀdicyanoꢀ2ꢀhydroxyphenyl)butꢀ2ꢀenecarbꢀ
oxylate 5 (62%) in the ratio 2 : 3 (Scheme 2). The process
in THF is more deep and results in the reduction of the
double bond in butene 5 to yield ethyl 2ꢀ(4,5ꢀdicyanoꢀ2ꢀ
hydroxyphenyl)butanoate 6 (58%).
It is known from the literature that a carbonyl group
can be reduced with NaBH4 to the corresponding alcohols
in dioxane,3 in acetic acid,4 in alcohols,5,6 with additives
of cobalt, palladium, and lanthanide salts,6,7 in alcohols
in the presence of iodine,8 ZnCl2 in THF. Reductions
9
of benzofuran ring to 2,3ꢀdihydrobenzofuran with sodiꢀ
um amalgam or catalytically with hydrogen10 are also
described, but some of these methods require prolong
heating and are accompanied by reduction of cyano
groups.6,8
The purpose of the present work is to develop selective
methods for the reduction of the carbonyl group in 3ꢀRꢀcarbꢀ
onylꢀsubstituted 5,6ꢀdicyanobenzofurans with NaBH4,
with the cyano groups remaining intact and leading to the
synthesis of 3ꢀhydroxymethylꢀsubstituted 5,6ꢀdicyanobenzoꢀ
furans earlier unreported in literature.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1693—1696, August, 2011.
1066ꢀ5285/11/6008ꢀ1719 © 2011 Springer Science+Business Media, Inc.

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Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
Chirkova et al.
Scheme 1
NOESY spectrum for compound 3b. Analysis of the specꢀ
trum showed that there are no contacts between the 2ꢀCH3
protons and H(2″) and H(6″) protons of the phenyl subꢀ
stituent, whereas the crossꢀpeaks between the H(2) and
H(3) atoms have low intensity, that allows us to draw
a conclusion on the transꢀarrangement of these substituꢀ
ents. This agrees with the literature data12,13 for similar
compounds, whose constants have the following values
Jtrans 7 Hz and Jcis 8—9 Hz. It was found that reduction
of the double bond is diastereoselective to yield only
transꢀisomer 3b—d with the spinꢀspin coupling constant
J2,3 = 6.7—7.3 Hz.
We failed in separation of compound 5 to individual
isomers by column chromatography. The ratio of isomers
of compound 5 (E/Z 2/3) was determined from the inteꢀ
1
gral intensities of a double set of signals in the H NMR
1—4: R = Me (a), 4ꢀC6H4OMe (b), 4ꢀC6H4Me (c), 2ꢀthienyl (d)
i. EtOH or THF.
spectrum, assignments of signals were made based on the
NOESY spectrum, which showed a correlation between
the methyl proton at the double bond and the lowꢀfield
hydroxyl proton in phthalonitrile.
Scheme 2
The studies performed showed that 3ꢀRꢀcarbonylꢀsubꢀ
stituted 5,6ꢀdicyanobenzofurans are selectively reduced
with NaBH4 in ethanol to the substituted 3ꢀRꢀ(hydroxymꢀ
ethyl)ꢀ5,6ꢀdicyanoꢀ2ꢀmethylbenzofurans. In THF, in adꢀ
dition to the indicated target compounds, products of more
deep reduction, viz., transꢀ3ꢀRꢀ(hydroxymethyl)ꢀ5,6ꢀdiꢀ
cyanoꢀ2ꢀmethylꢀ2,3ꢀdihydrobenzofurans and 3ꢀalkylꢀsubꢀ
stituted 4ꢀhydroxyphthalonitriles are formed.
Experimental
IR spectra of suspensions in Nujol were recorded on a Perkin—
Elmer RXꢀ1 spectrometer with the wavelength 700—4000 cm–1
.
Mass spectra were recorded on a FINNIGAN MAT INCOS 50
massꢀspectrometer (70 eV). NMR spectra were recorded on
a Bruker DRXꢀ500 spectrometer for solutions in DMSOꢀd6 at
30 °C. Signals for the residual protons in the solvents were referꢀ
The structures of new compounds were confirmed by
a combination of the IR and NMR spectroscopic and mass
spectrometric data. It should be noted that not all the
compounds gave a molecular ion, that is due to the instaꢀ
bility of the compounds under electron impact.
ences for the chemical shifts in the proton spectra (Δδ 2.50),
H
signals for DMSOꢀd6, in the carbon spectra (Δδ 39.5). The
C
standard Bruker procedures were used for twoꢀdimensional spectra.
The time of mixing in the NOESY spectra was 0.3 s.
Synthesis of compounds 2a—d and 5 (general procedure). Soꢀ
dium borohydride (0.0044 mol) was added to a suspension of
compound 1 (0.002 mol) in EtOH (3 mL) and the mixture was
stirred at 20—25 °C for 0.5 h, then it was poured into 1% aqueous
HCl (10 mL). A resinous precipitate that formed was extracted
with dichloromethane, the extract was thoroughly washed with
water and subjected to chromatography on silica gel (eluent:
hexane—ethyl acetate, 2 : 1). The eluent was evaporated, a preꢀ
cipitate was filtered off and recrystallized from EtOH.
1
The H NMR data showed that formation of comꢀ
pounds 2 leads to the appearance of closely positioned
signals for the OH and H(1´) protons in the region δ 5.0—6.5
as a pair of doublets with the common constant 4.0—4.5 Hz.
For more accurate assignment of signals for the protons in
compound 2a, we recorded an 1Hꢀ1Hꢀcorrelation NOESY
spectrum. Analysis of the crossꢀpeaks for the protons OH,
H(1´), 2´ꢀMe (the contacts with both one of the protons
in the phthalonitrile ring and the protons of the 2ꢀMe
group are observed) allowed us to draw a conclusion that
the OH group is at position 3 and to accurately assign the
phthalonitrile protons.
Compound 5 was additionally purified by the acidꢀbase reꢀ
precipitatation from water and isolated as a hydrate.
Synthesis of compounds 2a—d, 4a—d, and 6 (general proceꢀ
dure). Sodium borohydride (0.0044 mol) was added to a suspenꢀ
sion of compound 1 (0.002 mol) in THF (3 mL) and the mixture
was stirred at 20—25 °C for 2 h, then it was poured into 1% aq.
HCl (10 mL). A resinous precipitate that formed was extracted
For determination of cisꢀ or transꢀarrangement of proꢀ
1
tons in the furan ring, we recorded an Hꢀ1H correlation

Reduction of substituted 5,6ꢀdicyanobenzofurans
Russ.Chem.Bull., Int.Ed., Vol. 60, No. 8, August, 2011
1721
with dichloromethane, the extract was thoroughly washed with
water. Individual compounds were separated by preparative
column chromatography (silica gel was a stationary phase, hexꢀ
ane—ethyl acetate (2 : 1) was an eluent). The eluent was evapoꢀ
rated, a precipitate was filtered off and recrystallized from EtOH.
3ꢀ(1ꢀHydroxyethyl)ꢀ2ꢀmethylꢀ1ꢀbenzofuranꢀ5,6ꢀdicarboniꢀ
trile (2a). The yield was 67%, m.p. 134—136 °C (from ethanol).
Found (%): C, 68.74; H, 4.20; N, 12.18. C13H10N2O2. Calculatꢀ
ed (%): C, 69.02; H, 4.46; N, 12.38. IR (ν/cm–1): 3199 (OH);
2233 (C≡N); 1613 (Ar); 1596; 1234 (C—O—C). MS (EI, 70 eV),
m/z (Irel (%)): 226 [M+] (27.4), 211 [M+ – Me] (100), 181
[M+ – MeCHOH] (14.7). 1H NMR (DMSOꢀd6), δ: 1.45 (d, 3 H,
2´ꢀCH3, J = 6.5 Hz); 2.54 (s, 3 H, 2ꢀCH3); 5.05 (dq, 1 H, H(1´),
J = 3.8 Hz, J = 6.5 Hz); 5.40 (d, 1 H, OH, J = 3.8 Hz); 8.41
(s, 1 H, H(7)); 8.45 (s, 1 H, H(4)).
3ꢀ[Hydroxy(4ꢀmethoxyphenyl)methyl]ꢀ2ꢀmethylꢀ1ꢀbenzofuꢀ
ranꢀ5,6ꢀdicarbonitrile (2b). The yield was 76%, m.p. 139—141 °C.
Found (%): C, 71.36; H, 4.22; N, 8.75. C19H14N2O3. Calculatꢀ
ed (%): C, 71.69; H, 4.43; N, 8.80. IR (ν/cm–1): 3491 (OH);
2232 (C≡N); 1612 (Ar); 1511; 1283 (C—O—C). MS (EI, 70 eV),
m/z (Irel (%)): 318 [M+] (10.5), 301 [M+ – OH] (14.6), 209, 181
[M+ – CHOH – 4ꢀMeꢀC6H4] (18.6), 137 [+CHOH – 4ꢀMeꢀ
C6H4] (17.8), 109 (100). 1H NMR (DMSOꢀd6), δ: 2.58 (s, 3 H,
CH3); 3.72 (s, 3 H, OMe); 6.01 (d, 1 H, OH, J = 2.6 Hz); 6.07
(br.s, 1 H, CH); 6.89 (d, 2 H, H(3´), H(5´), J = 8.3 Hz); 7.38
(d, 2 H, H(2´), H(6´), J = 8.3 Hz); 8.19 (s, 1 H, H(4)); 8.42
(s, 1 H, H(7)).
3ꢀ[Hydroxyꢀ(4ꢀmethylphenyl)methyl]ꢀ2ꢀmethylꢀ1ꢀbenzofuꢀ
ranꢀ5,6ꢀdicarbonitrile (2c). The yield was 68%, m.p. 150—152 °C
(from ethanol). Found (%): C, 75.18; H, 4.46; N, 9.15.
C19H14N2O2. Calculated (%): C, 75.48; H, 4.67; N, 9.27. IR
(ν/cm–1): 3490 (OH); 2224 (C≡N); 1611 (Ar); 1511 (Ar); 1273
(C—O—C). MS (EI, 70 eV), m/z (Irel (%)): 121 [CHOH –
– 4ꢀMeꢀC6H4+] (100), 91 [4ꢀMeꢀC6H4+] (56.6). 1H NMR
(DMSOꢀd6), δ: 2.26 (s, 3 H, 4´ꢀCH3); 2.58 (s, 3 H, 2ꢀCH3); 6.00
(d, 1 H, H(1´), J = 4.0 Hz); 6.09 (d, 1 H, OH, J = 4.0 Hz); 7.13
(d, 2 H, H(3´), H(5´), J = 7.7 Hz); 7.34 (d, 2 H, H(2´), H(6´),
J = 7.7 Hz); 8.17 (s, 1 H, H(4)); 8.42 (s, 1 H, H(7)).
3ꢀ[Hydroxy(2ꢀthienyl)methyl]ꢀ2ꢀmethylꢀ1ꢀbenzofuranꢀ5,6ꢀdiꢀ
carbonitrile (2d). The yield was 62%, m.p. 115—117 °C (from
ethanol). Found (%): C, 64.95; H, 3.40; N, 9.46. C16H10N2O2S.
Calculated (%): C, 65.29; H, 3.42; N, 9.52. IR (ν/cm–1): 3499
(OH); 2229 (C≡N); 1597 (Ar); 1284 (C—O—C). MS (EI, 70 eV),
m/z (Irel (%)): 294 [M+] (8.8), 277 [M+ – OH] (7.6), 209 (12.7),
182 [M+ – CHOH – C4H3S] (12.4), 111 (24.3), 85 (100).
1H NMR (DMSOꢀd6), δ: 2.60 (s, 3 H, CH3); 6.31 (d, 1 H,
H(1´), J = 4.4 Hz); 6.51 (d, 1 H, OH, J = 4.2 Hz); 6.96 (dd, 1 H,
H(4´), J = 3.5 Hz, J = 5.0 Hz); 6.99 (d, 1 H, H(5´), J = 3.5 Hz);
7.44 (dd, 1 H, H(3´), J = 1.3 Hz, J = 5.0 Hz); 8.23 (s, 1 H, H(4));
8.47 (s, 1 H, H(7)).
J = 4.4 Hz); 6.91 (d, 2 H, H(3´), H(5´), J = 8.7 Hz); 7.26
(d, 2 H, H(2´), H(6´), J = 8.7 Hz); 7.50 (s, 1 H, H(7)); 7.70
(s, 1 H, H(4)).
3ꢀ[Hydroxy(4ꢀmethylphenyl)methyl]ꢀ2ꢀmethylꢀ2,3ꢀdihydroꢀ
1ꢀbenzofuranꢀ5,6ꢀdicarbonitrile (3c). The yield was 28%, m.p.
147—149 °C (from ethanol). Found (%): C, 74.69; H, 5.06;
N, 8.91. C19H16N2O2. Calculated (%): C, 74.98; H, 5.30; N, 9.20.
IR (ν/cm–1): 3550 (OH); 2231 (C≡N); 1596 (Ar); 1257 (C—O—C).
+
MS (EI, 70 eV), m/z (Irel (%)): 121 [CHOH – 4ꢀMeꢀC6H4
]
1
(100), 91 [4ꢀMeꢀC6H4+] (46.2). H NMR (DMSOꢀd6), δ: 1.09
(d, 3 H, 2ꢀCH3, J = 6.3 Hz); 2.30 (s, 3 H, 4´ꢀCH3); 3.48 (dd, 1 H,
H(3), J = 6.3 Hz, J = 7.0 Hz); 4.72 (dd, 1 H, H(1´), J = 4.5 Hz,
J = 7.0 Hz); 4.78 (quint, 1 H, H(2), J = 6.3 Hz); 5.85 (d, 1 H,
OH, J = 4.5 Hz); 7.16 (d, 2 H, H(3´), H(5´), J = 8.0 Hz); 7.22
(d, 2 H, H(2´), H(6´), J = 8.0 Hz); 7.53 (s, 1 H, H(7)); 7.68 (s, 1 H,
H(4)). 13C NMR (DMSOꢀd6), δ: 20.74 (4´ꢀMe); 20.96 (2ꢀMe);
55.10 (C(3)); 73.47 (C(1″)); 84.09 (C(2)); 105.56 (C(5)); 114.54
(C(7)); 115.49 (C≡N); 116.00 (C≡N); 115.62 (C(6)); 126.73
(C(2´), C(6´)): 128.77 (C(3´)/C(5´)); 131.76 (C(4)); 135.79
(C(3a)); 136.78 (C(4´)); 138.99 (C(1´)); 162.96 (C(7a)).
3ꢀ[Hydroxy(2ꢀthienyl)methyl]ꢀ2ꢀmethylꢀ2,3ꢀdihydroꢀ1ꢀ
benzofuranꢀ5,6ꢀdicarbonitrile (3d). The yield was 18%, m.p.
143—146 °C (from ethanol). Found (%): C, 64.58; H, 3.89;
N, 9.34. C16H12N2O2S. Calculated (%):C, 64.85; H, 4.08; N, 9.45.
IR (ν/cm–1): 3560 (OH); 2220 (C≡N); 1244 (C—O—C). MS
(EI, 70 eV), m/z (Irel (%)): 296 [M+] (14.8), 184 [M+ – CH –
– OH – C4H3S] (24.4), 169 [M(184)+ – Me] (40.9), 113 [CH –
– OH – C4H3S+] (100). 1H NMR (DMSOꢀd6), δ: 1.20 (d, 3 H,
CH3, J = 6.4 Hz); 3.53 (dd, 1 H, H(3), J = 6.4 Hz, J = 6.7 Hz);
4.89 (quint, 1 H, H(2), J = 6.4 Hz); 5.10 (dd, 1 H, H(1´), J = 4.5 Hz,
J = 6.7 Hz); 6.34 (d, 1 H, OH, J = 4.5 Hz); 6.31 (br.d, 1 H,
H(1´), J = 4.2 Hz); 6.51 (d, 1 H, OH, J = 4.2 Hz); 6.94 (br.d, 1 H,
H(5´), J = 3.5 Hz); 6.99 (dd, 1 H, H(4´), J = 3.5 Hz, J = 5.0 Hz);
7.47 (dd, 1 H, H(5´), J = 1.2 Hz, J = 5.0 Hz); 7.55 (s, 1 H, H(4)),
7.74 (s, 1 H, H(7)). 13C NMR (DMSOꢀd6), δ: 11.74; 13.82;
23.76; 45.66; 60.32; 104.04; 114.34: 115.67: 116.31; 119.65;
132.54; 134.62; 159,43; 171.88.
4ꢀHydroxyꢀ5ꢀ{1ꢀ[hydroxy(4ꢀmethoxyphenyl)methyl]propyl}ꢀ
phthalonitrile (4b). The yield was 28%, m.p. 233—235 °C (from
ethanol). Found (%): C, 66.95; H, 5.72; N, 8.20. C19H18N2O3•
•H2O. Calculated (%): C, 67.05; H, 5.92; N, 8.23. IR (ν/cm–1):
3562 (OH); 2321 (C≡N); 1590, 1618 (Ar). 1H NMR (DMSOꢀd6),
δ: 0.61 (t, 3 H, CH3, J = 7.4 Hz); 1.46, 1.52 (both ddq, 1 H each,
CH2, J = 7.4 Hz, J = 13.8 Hz, J = 7.4 Hz); 3.28 (br.m, 1 H,
CHCH2); 3.78 (s, 3 H, 4´ꢀOCH3); 4.80 (d, 1 H, CHO, J = 7.4 Hz);
5.35 (br.s, 1 H, OH); 6.97 (d, 2 H, H(3´), H(5´), J = 8.5 Hz);
7.21 (d, 2 H, H(2´), H(6´), J = 8.5 Hz); 7.30 (s, 1 H, H(3)); 7.96
(s, 1 H, H(6)); 11.29 (br.s, 1 H, 4ꢀOH).
4ꢀHydroxyꢀ5ꢀ{1ꢀ[hydroxy(4ꢀmethylphenyl)methyl]propyl}ꢀ
phthalonitrile (4c). The yield was 38%, m.p. 240—242 °C (from
ethanol). Found (%): C, 70.19; H, 5.97; N, 8.41. C19H18N2O2•
•H2O. Calculated (%): C, 70.35; H, 6.21; N, 8.64. IR (ν/cm–1):
3ꢀ[Hydroxy(4ꢀmethoxyphenyl)methyl]ꢀ2ꢀmethylꢀ2,3ꢀdihydroꢀ
1ꢀbenzofuranꢀ5,6ꢀdicarbonitrile (3b). The yield was 38%, m.p.
153—155 °C (from ethanol). Found (%): C, 70.95; H, 4.86;
N, 8.59. C19H16N2O3. Calculated (%): C, 71.24; H, 5.03;
N, 8.74. IR (ν/cm–1): 3558 (OH), 2238 (C≡N); 1598 (Ar); 1253
(C—O—C). MS (EI, 70 eV), m/z (Irel (%)): 320 [M+] (2.4), 209,
183 [M+ – CHOH – 4ꢀMeOꢀC6H4] (10.6), 137 [+CHOH –
3560 (OH); 2320 (C≡N); 1592, 1610 (Ar). MS (EI, 70 eV), m/z
+
(Irel (%)): 121 [CHOH – 4ꢀMeꢀC6H4+] (100), 91 [4ꢀMeꢀC6H4
]
(49.0). 1H NMR (DMSOꢀd6), δ: 0.59 (t, 3 H, CH3, J = 7.4 Hz);
1.44, 1.50 (both ddq, 1 H each, CH2, J = 7.4 Hz, J = 13.8 Hz,
J = 7.4 Hz); 2.26 (s, 3 H, 4´ꢀCH3); 3.27 (br.s, 1 H, CHCH2);
4.81 (d, 1 H, CHO, J = 7.3 Hz); 5.37 (br.s, 1 H, OH); 7.07
(d, 2 H, H(3´), H(5´), J = 8.1 Hz); 7.11 (d, 2 H, H(2´), H(6´),
J = 8.1 Hz); 7.28 (s, 1 H, H(3)); 7.92 (s, 1 H, H(6)); 11.25
(br.s, 1 H, 4ꢀOH). 13C NMR (DMSOꢀd6), δ: 11.93 (1´ꢀCH3);
1
– 4ꢀMeOꢀC6H4] (100). H NMR (DMSOꢀd6), δ: 1.10 (d, 3 H,
2ꢀCH3, J = 6.4 Hz); 3.47 (dd, 1 H, H(3), J = 6.3 Hz, J = 7.3 Hz);
3.75 (s, 3 H, OCH3); 4.70 (dd, 1 H, H(1´), J = 4.4 Hz, J = 7.3 Hz);
4.77 (qd, 1 H, H(2), J = 6.4 Hz, J = 6.3 Hz); 5.77 (d, 1 H, OH,

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Chirkova et al.
21.08 (4″ꢀCH3); 24.43 (C(2´)); 47.30 (C(3´)); 74.62 (C(4´));
103.97 (C(1)); 113.11 (C(2)); 116.45 (C≡N); 117.24 (C≡N);
119.27 (C(3)); 126.80 (C(2″)/C(6″)); 128.71 (C(3″)/C(5″));
135.57 (C(5)); 136.19 (C(6)); 137.18 (C(1″)); 141.79 (C(4″));
160.79 (C(4)).
A mixture of E/Zꢀisomers 5 in the ratio 2 : 3. The yield was
62%, m.p. 124—126 °C (from hexane). Found (%): C, 61.13;
H, 5.02; N, 10.15. C14H12N2O3•H2O. Calculated (%): C, 61.31;
H, 5.14; N, 10.21. MS (EI, 70 eV), m/z (Irel (%)): 256 [M+]
(8.7), 210 [M+ – OEt] (91.3), 195 [M+ – OEt – Me] (47.8), 181
[M+ – OEt – Me – OH] (100).
Ethyl (2Z)ꢀ2ꢀ(4,5ꢀdicyanoꢀ2ꢀhydroxyphenyl)butꢀ2ꢀenecarbꢀ
oxylate (Zꢀ5). 1H NMR (DMSOꢀd6), δ: 1.15 (t, 3 H, CH3,
J = 7.1 Hz); 2.05 (d, 3 H, 4ꢀCH3, J = 7.2 Hz); 4.13 (q, 2 H, CH2,
J = 7.1 Hz); 6.45 (q, 1 H, H(3), J = 7.2 Hz); 7.3 (s, 1 H, H(3´));
7.91 (s, 1 H, H(6´)); 11.75 (s, 1 H, OH).
Ethyl (2E)ꢀ2ꢀ(4,5ꢀdicyanoꢀ2ꢀhydroxyphenyl)butꢀ2ꢀenecarbꢀ
oxylate (Eꢀ5). 1H NMR (DMSOꢀd6), δ: 1.16 (t, 3 H, CH3,
J = 7.1 Hz); 1.66 (d, 3 H, 4ꢀCH3, J = 7.2 Hz); 4.11 (q, 2 H, CH2,
J = 7.1 Hz); 7.13 (q, 1 H, H(3), J = 7.2 Hz); 7.4 (s, 1 H, H(3´));
7.83 (s, 1 H, H(6´)); 11.75 (s, 1 H, OH).
Ethyl 2ꢀ(4,5ꢀdicyanoꢀ2ꢀhydroxyphenyl)butanoate (6). The
yield was 58%, m.p. 160—162 °C (from hexane). Found (%):
C, 60.68; H, 5.72; N, 10.01. C14H14N2O3•H2O. Calculated (%):
C, 60.86; H, 5.84; N, 10.14. IR (ν/cm–1): 3546 (OH); 2233
(C≡N); 1598, 1615 (Ar). MS (EI, 70 eV), m/z (Irel (%)): 258
[M+] (39.5), 212 [M+ – C2H5OH] (100), 184 [M+ – C2H5OH –
– Et] (81), 169 (34), 157 (98), 141 (22), 102 (25), 76 (10).
1H NMR (DMSOꢀd6), δ: 0.80 (d, 3 H, 4ꢀCH3, J = 7.4 Hz); 1.12
(d, 3 H, OCH2CH3, J = 7.1 Hz); 1.77 (ddq, 1 H, 3ꢀCH2, J = 7.5 Hz,
J = 14.1 Hz, J = 7.4 Hz); 1.98 (ddq, 1 H, 3ꢀCH2, J = 7.5 Hz,
J = 14.1 Hz, J = 7.4 Hz); 3.82 (t, 1 H, H(2), J = 7.4 Hz, J = 7.5 Hz);
4.06 (q, 2 H, OCH2, J = 7.1 Hz); 7.33 (s, 1 H, H(3´)); 7.87
(s, 1 H, H(6´)); 11.74 (s, 1 H, OH).
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Received November 12, 2010;
in revised form May 11, 2011