Preparative synthesis of 2-[3-alkoxy-4-(hydroxy, alkoxy, acyloxy)phenyl]-1H-benzimidazoles proceeding from substituted benzaldehydes

Article abstract of DOI:10.1134/S1070428010020211

New functionally-substituted 2-[3-alkoxy-4-(hydroxy, alkoxy, acyloxy)phenyl]-1H-benzimidazoles were synthesized in preparative yields from aldehydes of vanillin series, their ethers and esters by the reaction with 1,2-phenylenediamine in the presence of s

Full text of DOI:10.1134/S1070428010020211

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 2, pp. 268−273. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © E.A. Dikusar, V.I. Potkin, 2009, published in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 2, pp. 273−278.
Preparative Synthesis of 2-[3-Alkoxy-4-(hydroxy, alkoxy,
acyloxy)phenyl]-1H-benzimidazoles Proceeding from Substituted
Benzaldehydes
E. A. Dikusar and V. I. Potkin
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus,
Minsk, 220072 Belarus
e-mail: evgen_58@mail.ru
Received May 6, 2009
Abstract—New functionally-substituted 2-[3-alkoxy-4-(hydroxy, alkoxy, acyloxy)phenyl]-1H-benzimidazoles were
synthesized in preparative yields from aldehydes of vanillin series, their ethers and esters by the reaction with 1,2-
phenylenediamine in the presence of sodium hydrogen sulfite in DMF solution at 80°C.
DOI: 10.1134/S1070428010020211
We formerly reported on the synthesis of 2-[3-alkoxy-
4-(hydroxy, alkoxy, acyloxy)phenyl]-2,3-dihydro-1H-
benzimidazoles, unstable compounds quickly darkening
in the light and at contact with the air oxygen with the
formation of tarry products [1]. Yet it is known that many
functionally substituted 1H-benzimidazoles are stable
compounds exhibiting a high antiviral action; the latter
fact stimulates the studies on their synthesis [2]. However
our attempts failed to adjust the procedure of synthesis
of 1H-benzimidazoles published in [2] that was aimed to
preparation of semimicro quantities of the target products
(up to 0.5 mmol) for the preparative synthesis of
functionally substituted 2-[3-alkoxy-4-(hydroxy, alkoxy,
acyloxy)phenyl]-1H-benzimidazoles IIIa–IIIv, IVa–IVl
using benzaldehydes of the vanillin series, their ethers
and esters I.
The target of the present study was the development
of a preparative synthesis of functionally substituted
2-[3-alkoxy-4-(hydroxy, alkoxy, acyloxy)phenyl]-1H-
benzimidazoles IIIa–IIIv, IVa–IVl by oxidative
condensation of benzaldehydes of the vanillin series, their
ethers and esters I with 1,2-phenylenediamine (II) in the
presence of a mild and selective oxidant, sodium hydrogen
sulfite, in DMF solution at 80°C. We employed the
R
O
N
O
CHO
C
C
H
N
H2N
N
H
N
DMF, NaHSO3
R
C
R',
+
_NaHS
N
H2N
R
O
O
R
R'
I
N
H
IIIa_IIIu, IVa_IVk
II
IIIv, IVl
III, R = H, R1 = MeO (a); R = MeO, R1 = HO (b), MeO (c), MeC(O)O (d), EtC(O)O (e), PrC(O)O (f), Me2CHC(O)O (g), BuC(O)O
(h), Me2CHCH2C(O)O (i), Me(CH2)6C(O)O (j), Me(CH2)8C(O)O (k), Me(CH2)16C(O)O (l), H2C=C(Me)C(O)O (m),
C6H5CH2C(O)O (n), C6H5CH(Me)CH2C(O)O (o), C6H5C(O)O (p), 2,4-Cl2C6H3C(O)O(q), 4-BrC6H4C(O)O (r), 3-O2NC6H4C(O)O
(s), MeOC(O)O (t), EtOC(O)O (u); R = MeO (v); IV, R = EtO, R1 = HO (a), MeO (b), MeC(O)O (c), EtC(O)O (d), PrC(O)O (e),
Me2CHC(O)O (f), BuC(O)O (g), Me2CHCH2C(O)O (h), 4-MeC6H4C(O)O (i), MeOC(O)O (j), EtOC(O)O (k); R = EtO (l).
268

PREPARATIVE SYNTHESIS OF 2-[3-ALKOXY-4-(HYDROXY,ALKOXY,ACYLOXY)PHENYL]-...
269
preparative stoichiometric ratio of reagents (5 mol of
aldehyde I, 5 mol of phenylenediamine II, and 1.67 mmol
of NaHSO3), the reaction time was 1 h. The yields of
target compounds IIIa–IIIv, IVa–IVl attained 75–85%.
The sodium hydrogen sulfite in the course of the oxidative
condensation was quantitatively reduced to sodium
hydrogen sulfide as was proved by the gravimetric
determination of S2– after its precipitation in the form of
ZnS from the water solutions obtained after the isolation
of compounds IIIa and IVa [3].
sulfite, and 2 ml of DMF was stirred for 1 h at 80°C,
cooled to 20–23°C, and diluted with 20 ml of methanol to
prevent too fast coagulation of a precipitate, the solution
obtained was added dropwise over 30–45 min to 200 ml
of distilled water at vigorous stirring. In the syntheses of
compounds IIIv and IVl per 5 mol of initial dialdehyde I
was taken a double amount of the other reagents. The
separated fine crystalline precipitate of compounds IIIa–
IIIv, IVa–IVl was filtered off, washed with water, and
dried in air at 20–23°C for 5–7 days.
The obtained compounds IIIa–IIIv, IVa–IVl are
stable yellow crystalline substances, their structure was
confirmed by elemental analysis, measurement of the
molecular mass by cryoscopy and GC-MS method, and
2-(4-Methoxyphenyl)-1H-benzimidazole (IIIa).
Yield 76%, mp 222–223°C. IR spectrum, cm–1: 3085,
3054, 3033, 3005 (CHarom); 2952, 2923, 2855, 2835
(CHaliph); 1627 (C=N); 1611, 1501 (C=Carom); 1296, 1255,
1179, 1125, 1034, 966 (CO); 845, 790, 760, 746, 740
(CHarom). UV spectrum, λmax, nm (ε): 213 (14000), 250
1
IR, UV, H NMR spectra. The purity of compounds
1
obtained according to H NMR spectra and GC-MS
analysis reached 95±1%. Functionally substituted 2-[3-
alkoxy-4-(hydroxy, alkoxy, acyloxy)phenyl]-1H-
benzimidazoles IIIa–IIIv, IVa–IVl are interesting for
testing their biological activity [4].
1
(9000), 305 (16000). H NMR spectrum, δ, ppm: 3.84 s
(3H, MeO), 6.95–8.25 m (9H, NH and Harom). Mass
spectrum: m/z 224 [M]+. Found, %: C 75.17; H 5.53;
N 2.13. M 216.8. C14H12N2O. Calculated, %: C 74.98;
H 5.39; N 12.49. M 224.3.
EXPERIMENTAL
4-(1H-Benzimidazol-2-yl)-2-methoxyphenol
(IIIb). Yield 78%, mp 84–85°C. IR spectrum, cm–1: 3405
(OH); 3060, 3030, 3004 (CHarom); 2960, 2927, 2852
(CHaliph); 1624 (C=N); 1601, 1515, 1501, 1495 (C=Carom);
1274, 1213, 1154, 1124, 1032 (CO); 870, 815, 746 (CHarom).
UV spectrum, λmax, nm (ε): 218 (18000), 302 (10000),
358 (1000). 1H NMR spectrum, δ, ppm: 3.74 s (3H,
MeO), 5.39 s (1H, OH), 6.60–7.95 m (8H, NH and
Harom). Found, %: C 70.28; H 5.17; N 11.32. M 228.4.
C14H12N2O2. Calculated, %: C 69.99; H 5.03; N 11.66.
M 240.3.
IR spectra were recorded on an IR Fourier
spectrophotometer Nicolet Protege-460 from pellets with
KBr, UV spectra were taken on a spectrophotometer
Specord UVVis from 1 × 10–4 M solutions of compounds
in methanol. 1H NMR spectra were registered on a spec-
trometer Tesla BS-587A (100 MHz) from 5% solutions
in DMSO-d6 or deuterochloroform, the chemical shifts
were measured from an internal reference TMS. Mass
spectra were obtained on a GC-MS instrument Hewlett
Packard 5890/5972 in the electron impact ionization mode
at the electrons energy 70 eV; capillary column HP-5MS
30 m×0.25 mm, stationary phase (5% PhMe Silicone)
0.25 μm, vaporizer temperature 250°C. Elemental
analyses were carried out on a C,H,N,O,S-analyzer
Elementar Vario EL-III, error of the determination 0.1%.
The molecular mass of compounds was measured by
cryoscopy in benzene.
2-(3,4-Dimethoxyphenyl)-1H-benzimidazole
(IIIc). Yield 80%, mp 83–84°C. IR spectrum, cm–1: 3060,
2999 (CHarom); 2960, 2932, 2901, 2835 (CHaliph); 1623
(C=N); 1605, 1591, 1503 (C=Carom); 1264, 1233, 1176,
1138, 1023 (CO); 860, 810, 765, 744 (CHarom). UV
spectrum, λmax, nm (ε): 219 (18000), 306 (14000), 358
1
(1000). H NMR spectrum, δ, ppm: 3.90 s (3H, 3-MeO),
3.93 s (3H, 4-MeO), 6.80–7.78 m (8H, NH and Harom).
Mass spectrum: m/z 254 [M]+. Found, %: C 71.09; H
5.58; N 10.82. M 244.0. C15H14N2O2. Calculated, %: C
70.85; H 5.55; N 11.02. M 254.3.
The vanillin and vanillal esters I were obtained by
procedures [5–8], 1,2-phenylenediamine (II) used was
of “pure for analysis” grade, purity 98%, mp 102–103°C,
sodium hydrogen sulfite was of “pure” grade, purity 97%.
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl
acetate (IIId). Yield 84%, mp 95–96°C. IR spectrum,
cm–1: 3061, 3009 (CHarom); 2961, 2935, 2848 (CHaliph);
1766 (C=O); 1624 (C=N); 1501 (C=Carom; 1268, 1214,
1197, 1214, 1197, 1173, 1122, 1032, 1010 (CO); 877, 830,
766, 746 (CHarom). UV spectrum, λmax, nm (ε): 217
2-[3-Alkoxy-4-(hydroxy, alkoxy, acyloxy)phenyl]-
1H-benzimidazoles IIIa–IIIv, IVa–IVl. General
procedure. A mixture of 5 mol of the functionally
substituted benzaldehyde of the vanillin series I, 5 mol of
1,2-phenylenediamine (II), 1.67 mol of sodium hydrogen
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DIKUSAR, POTKIN
270
(21000), 242 (7000), 280 (13000), 308 (14000), 320 (7000).
1H NMR spectrum, δ, ppm: 2.29 c (3H, Me), 3.92 c (3H,
MeO), 6.85–8.00 m (8H, NH and Harom). Mass spectrum:
m/z 282 [M]+. Found, %: C 68.41; H 5.19; N 9.64.
M 273.6. C16H14N2O3. Calculated, %: C 68.08; H 5.00;
N 9.92. M 282.3.
1501 (C=Carom); 1267, 1231, 1202, 1171, 1127, 1096, 1031
(CO); 868, 825, 784, 762, 744 (CHarom). UV spectrum,
λ
max, nm (ε): 219 (20000), 243 (8000), 282 (13000), 308
(15000), 320 (7000). 1H NMR spectrum, δ, ppm: 0.98 t
(3H, Me), 1.12–1.95 m [4H, (CH2)2], 2.56 t[2H,
CH2C(O)], 3.92 s (3H, MeO), 6.85–8.04 m (8H, NH
and Harom). Mass spectrum: m/z 324 [M]+. Found, %:
C 70.73; H 6.28; N 8.19. M 315.9. C19H20N2O3.
Calculated, %: C70.35; H 6.21; N 8.64. M 324.4.
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl
propionate (IIIe). Yield 82%, mp 44–45°C. IR
spectrum, cm–1: 3062, 3002 (CHarom); 2978, 2940, 2922,
2883, 2850 (CHaliph); 1763 (C=O); 1624 (C=N); 1606,
1501 (C=Carom); 1267, 1203, 1172, 1129, 1075, 1032 (CO);
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl
isovalerate (IIIi). Yield 77%, mp 103–104°C. IR
spectrum, cm–1: 3067, 3035, 3007 (CHarom); 2972, 2938,
2877, 2847 (CHaliph); 1758 (C=O); 1624 (C=N); 1607,
1593, 1504 (C=Carom); 1268, 1244, 1174, 1126, 1093, 1033
(CO); 867, 814, 783, 765, 743 (CHarom). UV spectrum,
884, 860, 830, 809, 760, 756 (CHarom). UV spectrum, λmax
,
nm (ε): 218 (21000), 242 (7000), 280 (13000), 308
(14000), 320 (7000). 1H NMR spectrum, δ, ppm: 1.16 t
(3H, Me), 2.55 q (2H, CH2), 3.91 s (3H, MeO), 6.85–
8.00 m (8H, NH and Harom). Mass spectrum: m/z 296
[M]+. Found, %: C69.20; H 5.48; N 9.12. M 282.7.
C17H16N2O3. Calculated, %: C 68.91; H 5.44; N 9.45.
M 296.3.
λ
max, nm (ε): 218 (22000), 243 (8000), 280 (14000), 308
(14000), 320 (7000). 1H NMR spectrum, δ, ppm: 1.14 d
(6H, Me2C), 1.45–2.92 m (3H, CH and CH2), 3.92 s (3H,
MeO), 6.85–8.00 m (8H, NH and Harom). Mass spectrum:
m/z 324 [M]+. Found, %: C 70.78; H 6.22; N 8.36. M
318.0. C19H20N2O3. Calculated, %: C 70.35; H 6.21; N
8.64. M 324.4.
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl
butyrate (IIIf). Yield 85%, mp 54–55°C. IR spectrum,
cm–1: 3061, 3007 (CHarom); 2964, 2934, 2874, 2847
(CHaliph); 1762 (C=O); 1624 (C=N); 1606, 1596, 1501
(C=Carom); 1267, 1240, 1203, 1171, 1128, 1094, 1031 (CO);
871, 832, 802, 760, 744 (CHarom). UV spectrum, λmax, nm
(ε): 219 (21000), 242 (8000), 280 (13000), 308 (14000),
320 (7000). 1H NMR spectrum, δ, ppm: 1.03 t (3H, Me),
1.77 m (2H, MeCH2), 2.54 t [2H, CH2C(O)], 3.91 s (3H,
MeO), 6.84–8.00 m (8H, NH and Harom). Mass spectrum:
m/z 310 [M]+. Found, %: C 69.95; H 5.92; N 8.87.
M 301.4. C18H18N2O3. Calculated, %: C 69.66; H 5.85;
N 9.03. M 310.4.
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl
caproate (IIIj). Yield 79%, mp 59–60°C. IR spectrum,
cm–1: 3062, 3040, 3025, 3015, 3003 (CHarom); 2955, 2927,
2867, 2855 (CHaliph); 1756 (C=O); 1624 (C=N); 1606,
1504 (C=Carom); 1269, 1246, 1200, 1172, 1131, 1104, 1033
(CO); 870, 825, 760, 745 (CHarom). UV spectrum, λmax
,
nm (ε): 218 (23000), 243 (8000), 280 (14000), 308
(14000), 320 (7000). 1H NMR spectrum, δ, ppm: 0.94 t
(3H, Me), 1.34 m [8H, (CH2)4], 1.82 m (2H, MeCH2),
2.60 t [2H, CH2C(O)], 3.92 s (3H, MeO), 6.84–8.00 m
(8H, NH and Harom). Mass spectrum: m/z 366 [M]+.
Found, %: C 72.56; H 7.28; N 7.30. M 352.5.
C22H26N2O3. Calculated, %: C 72.11; H 7.15; N 7.64.
M 366.5.
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl
isobutyrate (IIIg). Yield 82%, mp 94–95°C. IR
spectrum, cm–1: 3066, 3035, 3007 (CHarom); 2972, 2937,
2877, 2847 (CHaliph); 1759 (C=O); 1624 (C=N); 1607,
1592, 1504 (C=Carom); 1268, 1242, 1202, 1174, 1126, 1093,
1033 (CO); 867, 813, 783, 765, 743 (CHarom). UV
spectrum, λmax, nm (ε): 218 (21000), 243 (8000), 280
(13000), 308 (14000), 320 (7000). 1H NMR spectrum, δ,
ppm: 1.38 d (6H, Me2C), 2.90 m (1H, CH), 3.92 s (3H,
MeO), 6.84–8.02 m (8H, NH and Harom). Mass spectrum:
310 [M]+. Found, %: C 69.98; H 5.96; N 8.80. M 303.2.
C18H18N2O3. Calculated, %: C 69.66; H 5.85; N 9.03.
M 310.4.
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl
octanoate (IIIk). Yield 78%, mp 43–44°C. IR spectrum,
cm–1: 3060, 3005 (CHarom); 2954, 2925, 2854 (CHaliph);
1764 (C=O); 1624 (C=N); 1606, 1503 (C=Carom); 1270,
1232, 1202, 1175, 1134, 1106, 1034 (CO); 885, 860, 840,
812, 765, 745 (CHarom). UV spectrum, λmax, nm (ε): 218
(22000), 244 (8000), 280 (14000), 308 (14000), 320 (7000).
1H NMR spectrum, δ, ppm: 0.93 t (3H, Me), 1.35 m
[12H, (CH2)6], 1.84 m(2H, MeCH2), 2.60 t [2H,
CH2C(O)], 3.92 s (3H, MeO), 6.84–8.00 m (8H, NH
and Harom). Found, %: C 73.39; H 7.73; N 6.85. M 383.4.
C24H30N2O3. Calculated, %: C 73.07; H 7.66; N 7.10.
M 394.5.
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl
pentanoate (IIIh). Yield 80%, mp 41–42°C. IR
spectrum, cm–1: 3098, 3060, 3006 (CHarom); 2957, 2931,
2871 (CHaliph); 1762 (C=O); 1624 (C=N); 1606, 1593,
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PREPARATIVE SYNTHESIS OF 2-[3-ALKOXY-4-(HYDROXY,ALKOXY,ACYLOXY)PHENYL]-...
271
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl
stearate (IIIl). Yield 81%, mp 42–43°C. IR spectrum,
cm–1: 3076, 3060, 3004 (CHarom); 2965, 2918, 2850
(CHaliph); 1765 (C=O); 1624 (C=N); 1602, 1503
(C=Carom); 1268, 1240, 1202, 1174, 1128, 1031 (CO); 870,
835, 760, 745, 730 (CHarom). UV spectrum, λmax, nm (ε):
218 (2100), 243 (8000), 280 (1300), 308 (14000), 320
(600). 1H NMR spectrum, δ, ppm: 0.91 t(3H, Me), 1.10–
2.14 m [30H, (CH2)15], 2.68 t [2H, CH2C(O)], 3.92 s
(3H, MeO), 6.84–8.04 m (8H, NH and Harom). Found,
%: C 76.04; H 9.29; N 5.33. M 482.0. C32H46N2O3.
Calculated, %: C 75.85; H 9.15; N 5.53. M 506.7.
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl
benzoate (IIIp). Yield 85%, mp 82–83°C. IR spectrum,
cm–1: 3090, 3061, 3040, 3008 (CHarom); 2961, 2933, 2850
(CHaliph); 1743 (C=O); 1625 (C=N); 1501 (C=Carom);
1263, 1202, 1174, 1122, 1079, 1058, 1024 (CO); 872, 818,
799, 760, 746, 706, 685 (CHarom). UV spectrum, λmax, nm
1
(ε): 204 (30000), 210 (25000), 308 (16000). H NMR
spectrum, δ, ppm: 3.94 s (3H, MeO), 6.90–8.18 m (13H,
NH and Harom). Found, %: C 73.56; H 4.82; N 7.86.
M 331.8. C21H16N2O3. Calculated, %: C 73.24; H 4.68;
N 8.13. M 344.4.
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl 2,4-
dichlorobenzoate (IIIq). Yield 83%, mp 77–78°C. IR
spectrum, cm–1: 3090, 3069, 3009 (CHarom); 2960, 2924,
2851 (CHaliph); 1753 (C=O); 1625 (C=N); 1606, 1584,
1500 (C=Carom); 1266, 1236, 1199, 1173, 1147, 1121, 1085,
1031 (CO); 873, 822, 760, 744 (CHarom). UV spectrum,
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl
methacrylate (IIIm). Yield 80%, mp 119–120°C. IR
spectrum, cm–1: 3090, 3080, 3070, 3060, 3030, 3004
(CHarom); 2962, 2924, 2852 (CHaliph); 1739 (C=O); 1636
(C=C); 1624 (C=N); 1607, 1501 (C=Carom); 1267, 1203,
1175, 1126, 1032 (CO); 880, 820, 760, 745 (CHarom). UV
spectrum, λmax, nm (ε): 213 (24000), 244 (7000), 308
λ
max, nm (ε): 220 (40000), 244 (22000), 309 (16000).
1H NMR spectrum, δ, ppm: 3.94 s (3H, MeO), 6.90–
8.16 m (11H, NH and Harom). Found, %: C 61.32; H 3.58;
Cl 16.90; N 6.29. M 395.5. C21H14Cl2N2O3. Calculated,
%: C 61.03; H 3.41; Cl 17.16; N 6.78. M 413.3.
1
(13000). H NMR spectrum, δ, ppm: 2.10 s (3H, Me),
3.92 s (3H, MeO), 5.81 s and 6.41 s 1H and 1H, C=CH2),
6.85–8.00 m (8H, NH and Harom). Found, %: C 70.42; H
5.24; N 8.78. M 288.1. C18H16N2O3. Calculated, %:
C 70.12; H 5.23; N 9.09. M 308.3.
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl 4-
bromobenzoate (IIIr). Yield 84%, mp 108–109°C. IR
spectrum, cm–1: 3090, 3070, 3060, 3040, 3005 (CHarom);
2970, 2921, 2860, 2850 (CHaliph); 1740 (C=O); 1627
(C=N); 1609, 1589, 1508 (C=Carom); 1261, 1202, 1172,
1122, 1071, 1032, 1011 (CO); 876, 840, 804, 747 (CHarom).
UV spectrum, λmax, nm (ε): 203 (32000), 248 (22000),
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl
phenylacetate (IIIn). Yield 82%, mp 56–57°C. IR
spectrum, cm–1: 3090, 3070, 3045, 3006 (CHarom); 2961,
2934, 2849 (CHaliph); 1760 (C=O); 1624 (C=N); 1605,
1498 (C=Carom); 1267, 1233, 1202, 1174, 1120, 1030
(CO); 840, 827, 760, 745, 730, 700 (CHarom). UV
spectrum, λmax, nm (ε): 210 (30000), 245 (7000), 308
(12000). 1H NMR spectrum, δ, ppm: 3.82 s (2H, CH2),
3.93 s (3H, MeO), 6.90–8.00 m (13H, NH and Harom).
Found, %: C 74.10; H 5.13; N 8.49. M 343.7.
C22H18N2O3. Calculated, %: C 73.73; H 5.06; N 7.82.
M 358.4.
1
308 (18000). H NMR spectrum, δ, ppm: 3.94 s (3H,
MeO), 6.90–8.24 m (12H, NH and Harom). Found, %:
C 59.84; H 3.66; Br 18.31; N 6.34. M 415.7.
C21H15BrN2O3. Calculated, %: C 59.59; H 3.57; Br 18.88;
N 6.62. M 423.3.
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl 3-
nitrobenzoate (IIIs). Yield 83%, mp 70–71°C. IR
spectrum, cm–1: 3084, 3070, 3010 (CHarom); 2980, 2932,
2872, 2853 (CHaliph); 1746 (C=O); 1627 (C=N); 1616,
1608, 1500 (C=Carom); 1532, 1350 (NO2); 1291, 1254,
1201, 1175, 1114, 1056, 1032 (CO); 862, 811, 785, 746,
715 (CHarom). UV spectrum, λmax, nm (ε): 217 (34000),
242 (13000), 309 (16000). 1H NMR spectrum, δ, ppm:
3.94 s (3H, MeO), 6.90–8.42 m (12H, NH and Harom).
Found, %: C 65.06; H 3.87; N 10.30. M 380.1.
C21H15N3O5. Calculated, %: C 64.78; H 3.88; N 10.79.
M 389.4.
4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl 3-
phenylbutyrate (IIIo). Yield 80%, mp 59–60°C. IR
spectrum, cm–1: 3090, 3060, 3026, 3003 (CHarom); 2961,
2925, 2890, 2870, 2850 (CHaliph); 1759 (C=O); 1624
(C=N); 1605, 1499 (C=Carom); 1266, 1233, 1201, 1175,
1081, 1032 (CO); 880, 840, 765, 745, 700 (CHarom). UV
spectrum, λmax, nm (ε): 210 (29000), 244 (7000), 308
1
(12000). H NMR spectrum, δ, ppm: 1.45 d(3H, Me),
2.92 d (2H, CH2), 3.40 q (1H, CH), 3.93 s (3H, MeO),
6.90–8.00 m (13H, NH and Harom). Found, %: C 74.83;
H 5.80; N 7.00. M 372.5. C24H22N2O3. Calculated, %:
C 74.59; H 5.74; N 7.25. M 386.4.
[4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl]-
methylcarbonate (IIIt). Yield 77%, mp 58–59°C. IR
spectrum, cm–1: 3059, 3009 (CHarom); 2956, 2940, 2890,
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DIKUSAR, POTKIN
272
2848 (CHaliph); 1768 (C=O); 1625 (C=N); 1608, 1502
(C=Carom); 1259, 1204, 1176, 1124, 1056, 1030 (CHarom).
UV spectrum, λmax, nm (ε): 218 (21000), 242 (7000),
280 (13000), 308 (14000), 320 (7000). 1H NMR spectrum,
δ, ppm: 3.92 (3H, 3-MeO), 3.96s [3H, 4-MeOC(O)O],
6.84–8.00 m (8H, NH and Harom). Found, %: C 64.71; H
4.87; N 9.02. M 287.2. C16H14N2O4. Calculated, %:
C 64.42; H 4.73; N 9.39. M 298.3.
(CHarom). UV spectrum, λmax, nm (ε): 218 (17000), 305
1
(14000), 358 (1000). H NMR spectrum, δ, ppm: 1.28 t
(3H, Me), 3.82 s (3H, MeO), 3.90 q (2H, CH2O), 6.55–
7.85 m (8H, NH and Harom). Mass spectrum: m/z 268
[M]+. Found, %: C 71.92; H 6.16; N 10.05. M 258.7.
C16H16N2O2. Calculated, %: C 71.62; H 6.01; N 10.44.
M 268.3.
4-(1H-Benzimidazol-2-yl)-2-ethoxyphenyl
acetate (IVc). Yield 82%, mp 66–67°C. IR spectrum,
cm–1: 3060, 3038, 3002 (CHarom); 2979, 2928, 2901, 2845
(CHaliph); 1767 (C=O); 1627 (C=N); 1605, 1501
(C=Carom); 1269, 1212, 1187, 1123, 1040, 1010 (CO); 870,
830, 808, 760, 746 (CHarom). UV spectrum, λmax, nm (ε):
218 (22000), 243 (8000), 280 (14000), 308 (14000), 320
[4-(1H-Benzimidazol-2-yl)-2-methoxyphenyl]
ethylcarbonate (IIIu). Yield 79%, mp 50–51°C. IR
spectrum, cm–1: 3060, 3007 (CHarom); 2979, 2936, 2874,
2850 (CHaliph); 1764 (C=O); 1625 (C=N); 1608, 1503
(C=Carom); 1251, 1203, 1177, 1122, 1095, 1053, 1030 (CO);
860, 834, 803, 775, 765, 744 (CHarom). UV spectrum, λmax
,
1
(7000). H NMR spectrum, δ, ppm: 1.27 t (3H, Me),
nm (ε): 218 (22000), 243 (7000), 280 (12000), 308
(14000), 320 (7000). 1H NMR spectrum, δ, ppm: 1.45 t
(3H, Me), 3.92 s (3H, MeO), 4.18 q (2H, CH2), 6.85–
8.00 m (8H, NH and Harom). Found, %: C 65.70; H 5.26;
N 8.50. M 304.6. C17H16N2O4. Calculated, %: C 65.38;
H 5.16; N 8.97. M 312.3.
2.32 s (3H, Me), 3.95 q (2H, CH2O), 7.00–7.95 m (8H,
NH and Harom). Mass spectrum: m/z 296 [M]+. Found,
%: C 69.14; H 5.62; N 9.06. M 284.0. C17H16N2O3.
Calculated, %: C 68.91; H 5.44; N 9.45. M 296.3.
4-(1H-Benzimidazol-2-yl)-2-ethoxyphenyl
propionate (IVd). Yield 81%, mp 63–64°C. IR
spectrum, cm–1: 3059, 3025, 3006 (CHarom); 2980, 2939,
2898, 2880, 2850 (CHaliph); 1764 (C=O); 1627 (C=N);
1607, 1501 (C=Carom); 1268, 1173, 1125, 1076, 1042 (CO);
885, 835, 812, 760, 745 (CHarom). UV spectrum, λmax, nm
(ε): 219 (22000), 244 (7000), 292 (14000), 308 (16000),
325 (7000). 1H NMR spectrum, δ, ppm: 1.32 t [3H,
MeCH2C(O)], 1.37 t (3H, MeCH2O), 2.60 q [2H,
CH2C(O)], 4.14 q (2H, CH2O), 7.05–7.90 m (8H, NH
and Harom). Mass spectrum: m/z 310 [M]+. Found, %:
C69.93; H 5.99; N 8.86. M 301.6. C18H18N2O3.
Calculated, %: C 69.66; H 5.85; N 9.03. M 310.4.
Bis[4-(1H-benzimidazol-2-yl)-2-methoxyphenyl]
succinate (IIIv). Yield 80%, mp 92–93°C. IR spectrum,
cm–1: 3062, 3008 (CHarom); 2960, 2927, 2851 (CHaliph);
1762 (C=O); 1625 (C=N); 1606, 1501 (C=Carom); 1267,
1231, 1201, 1126, 1032 (CO); 883, 824, 806, 760, 746
(CHarom). UV spectrum, λmax, nm (ε): 216 (38000), 243
(12000), 280 (23000), 308 (20000), 318 (12000). 1H NMR
spectrum, δ, ppm: 3.06 s [4H, (CH2)2], 3.92 s (6H,
2MeO), 6.82–8.00 m (16H, 2NH and Harom). Found, %:
C 68.54; H 4.82; N 9.71. M 542.3. C32H26N4O6.
Calculated, %: C 68.32; H 4.66; N 9.96. M 562.6.
4-(1H-Benzimidazol-2-yl)-2-ethoxyphenol(IVa).
Yield 75%, mp 107–108°C. IR spectrum, cm–1: 3374
(OH); 3061, 3040, 3002 (CHarom); 2979, 2929, 2898, 2870,
2845 (CHaliph); 1628 (C=N); 1601, 1501 (C=Carom); 1271,
1232, 1209, 1125, 1041 (CO); 872, 810, 760, 746 (CHarom).
UV spectrum, λmax, nm (ε): 216 (18000), 304 (10000),
357 (1000). 1H NMR spectrum, δ, ppm: 1.27 t (3H,
Me), 4.06 q (2H, CH2O), 6.04 br.s(1H, OH), 6.60–7.93
m (8H, NH and Harom). Found, %: C 71.11; H 5.68;
N 10.86. M 243.5. C15H14N2O2. Calculated, %: C 70.85;
H 5.55; N 11.02. M 254.3.
4-(1H-Benzimidazol-2-yl)-2-ethoxyphenyl
butyrate (IVe). Yield 82%, mp 52–53°C. IR spectrum,
cm–1: 3065, 3049, 3004 (CHarom); 2970, 2933, 2878, 2855
(CHaliph); 1752 (C=O); 1627 (C=N); 1605, 1591, 1504
(C=Carom); 1270, 1247, 1198, 1134, 1108, 1096, 1041 (CO);
869, 823, 790, 760, 744 (CHarom). UV spectrum, λmax, nm
(ε): 222 (22000), 241 (15000), 290 (22000), 308 (24000),
321 (17000). 1H NMR spectrum, δ, ppm: 1.03 t [3H,
MeCH2C(O)], 1.37 t (3H, MeCH2O), 1.71 m (2H,
MeCH2CH2), 2.52 t [2H, CH2C(O)], 4.16 q (2H, CH2O),
7.05–8.00 m (8H, NH and Harom). Mass spectrum: m/z
324 [M]+. Found, %: C 70.74; H 6.35; N 8.28. M 313.8.
C19H20N2O3. Calculated, %: C 70.35; H 6.21; N 8.64.
M 324.4.
2-(4-Methoxy-3-ethoxyphenyl)-1H-benz-
imidazile (IVb). Yield 78%, mp 72–73°C. IR spectrum,
cm–1: 3060, 3030, 3002 (CHarom); 2982, 2928, 2902, 2880,
2860, 2840 (CHaliph); 1625 (C=N); 1606, 1590, 1501
(C=Carom); 1263, 1138, 1027 (CO); 878, 811, 766, 746
4-(1H-Benzimidazol-2-yl)-2-ethoxyphenyl
isobutyrate (IVf). Yield 80%, mp 161–162°C. IR
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PREPARATIVE SYNTHESIS OF 2-[3-ALKOXY-4-(HYDROXY,ALKOXY,ACYLOXY)PHENYL]-...
273
spectrum, cm–1: 3062, 3030, 3003 (CHarom); 2977, 2933,
2900, 2877, 2855 (CHaliph); 1763 (C=O); 1628 (C=N);
1608, 1592, 1500 (C=Carom); 1266, 1179, 1124, 1092, 1040
M 360.8. C23H20N2O3. Calculated, %: C 74.18; H 5.41;
N 7.52. M 372.4.
[4-(1H-Benzimidazol-2-yl)-2-ethoxyphenyl]
methylcarbonate (IVj). Yield 75%, mp 71–72°C. IR
spectrum, cm–1: 3060, 3030, 3004 (CHarom); 2980, 2956,
2931, 2898, 2853 (CHaliph); 1770 (C=O); 1626 (C=N);
1608, 1501 (C=Carom); 1259, 1197, 1125, 1055, 1039 (CO);
(CO); 866, 810, 761, 744 (CHarom). UV spectrum, λmax
,
nm (ε): 220 (22000), 242 (15000), 290 (21000), 308
1
(24000), 321 (16000). H NMR spectrum, δ, ppm: 1.35 d
(6H, Me2C), 1.42 t (3H, Me), 2.86 m (1H, CH), 4.16 q
(2H, CH2O), 7.02–8.00 m (8H, NH and Harom). Mass
spectrum: m/z 324 [M]+. Found, %: C 70.78; H 6.31;
N 8.37. M 316.3. C19H20N2O3. Calculated, %: C 70.35;
H 6.21; N 8.64. M 324.4.
874, 830, 820, 776, 767, 745 (CHarom). UV spectrum, λmax
,
nm (ε): 223 (22000), 241 (15000), 290 (22000), 308
(24000), 321 (17000). 1H NMR spectrum, δ, ppm: 1.27 t
(3H, Me), 3.95 q (2H, CH2O), 3.96 s (3H, MeO), 7.00–
7.94 m (8H, NH and Harom). Found, %: C 65.57; H 5.22;
N 8.64. M 313.6. C17H16N2O4. Calculated, %: C 65.38;
H 5.16; N 8.97. M 312.3.
4-(1H-Benzimidazol-2-yl)-2-ethoxyphenyl
valerate (IVg). Yield 84%, mp 138–139°C. IR spectrum,
cm–1: 3057, 3031, 3003 (CHarom); 2955, 2926, 2901, 2971,
2863 (CHaliph); 1766 (C=O); 1627 (C=N); 1608, 1595,
1503 (C=Carom); 1254, 1232, 1192, 1131, 1096, 1039 (CO);
893, 870, 830, 760, 755 (CHarom). UV spectrum, λmax, nm
(ε): 220 (23000), 242 (15000), 290 (21000), 307 (24000),
[4-(1H-Benzimidazol-2-yl)-2-ethoxyphenyl]
ethylcarbonate (IVk). Yield 77%, mp 56–57°C. IR
spectrum, cm–1: 3061, 3027, 3003 (CHarom); 2981, 2931,
2900, 2855 (CHaliph); 1765 (C=O); 1626 (C=N); 1608,
1503 (C=Carom); 1249, 1195, 1124, 1095, 1040 (CO); 867,
830, 809, 772, 760, 745 (CHarom). UV spectrum, λmax, nm
(ε): 222 (21000), 242 (15000), 290 (22000), 308 (24000),
1
321 (16000). H NMR spectrum, δ, ppm: 0.96–1.50 m
(6H, 2Me), 1.55–2.20 m [4H, (2CH2)2], 2.52 t [2H,
CH2C(O)], 4.16 q (2H, CH2O), 7.00–8.00 m (8H, NH
and Harom). Mass spectrum: m/z 338 [M]+. Found, %:
C 71.25; H 6.63; N 8.07. M 322.5. C20H22N2O3.
Calculated, %: C 70.99; H 6.55; N 8.28. M 338.4.
1
322 (17000). H NMR spectrum, δ, ppm: 1.20–1.72 m
(6H, 2Me), 4.00–4.54 m (4H, 2CH2O), 7.00–7.96 m (8H,
NH and Harom). Found, %: C 66.59; H 5.64; N 8.19.
M 318.2. C18H18N2O4. Calculated, %: C 66.25; H 5.56;
N 8.58. M 326.3.
4-(1H-Benzimidazol-2-yl)-2-ethoxyphenyl
isovalerate (IVh). Yield 81%, mp 56–57°C. IR
spectrum, cm–1: 3061, 3030, 3004 (CHarom); 2961, 2931,
2900, 2873, 2850 (CHaliph); 1761 (C=O); 1627 (C=N);
1607, 1501 (C=Carom); 1265, 1181, 1151, 1121, 1091, 1040
Bis[4-(1H-benzimidazol-2-yl)-2-ethoxyphenyl]
succinate (IVl). Yield 83%, mp 111–112°C. IR spectrum,
cm–1: 3062, 3030, 3002 (CHarom); 2979, 2928, 2897, 2855
(CHaliph); 1764 (C=O); 1627 (C=N); 1610, 1501
(C=Carom); 1265, 1232, 1194, 1123, 1039 (CO); 885, 838,
803, 762, 746 (CHarom). UV spectrum, λmax, nm (ε): 214
(39000), 242 (13000), 280 (24000), 308 (20000), 318
(CO); 867, 831, 766, 744 (CHarom). UV spectrum, λmax
,
nm (ε): 220 (24000), 243 (15000), 290 (22000), 307
1
(24000), 321 (16000). H NMR spectrum, δ, ppm: 1.12
d (6H, Me2C), 1.42 t (3H, Me), 1.40–2.90 m (3H, CH
and CH2), 4.15 q (2H, CH2O), 7.00–8.02 m (8H, NH
and Harom). Mass spectrum: m/z 338 [M]+. Found, %:
C 71.18; H 6.67; N 7.54. M 329.1. C20H22N2O3.
Calculated, %: C 70.99; H 6.55; N 8.28. M 338.4.
1
(13000). H NMR spectrum, δ, ppm: 1.26 t (6H, Me),
3.06 s [4H, (CH2)2], 3.95 q (4H, 2CH2O), 6.82–8.02 m
(16H, 2NH and Harom). Found, %: C 69.47; H 5.21;
N 9.18. M 576.7. C33H30N4O6. Calculated, %: C 69.14;
H 5.12; N 9.49. M 590.6.
4-(1H-Benzimidazol-2-yl)-2-ethoxyphenyl
4-methylbenzoate (IVi). Yield 80%, mp 86–87°C. IR
spectrum, cm–1: 3090, 3060, 3040, 3005 (CHarom); 2978,
2925, 2905, 2880, 2850 (CHaliph); 1741 (C=O); 1626
(C=N); 1610, 1504 (C=Carom); 1263, 1194, 1177, 1122,
1062, 1039, 1019 (CO); 873, 840, 830, 811, 760, 744
(CHarom). UV spectrum, λmax, nm (ε): 309 (30000), 340
REFERENCES
1. Dikusar, E.A., Kozlov, N.G., and Potkin, V.I., Zh. Obshch.
Khim., 2007, vol. 77, p. 1871.
2. Xiangming, Han, Huiqiang, Ma, Yulu, and Wang., Zh. Org.
Khim., 2008, vol. 44, p. 872.
1
(19000). H NMR spectrum, δ, ppm: 1.44 t (3H, MeCH2),
2.49 s (3H, MeC6H4), 4.18 q (2H, CH2O), 7.00–8.22 m
(12H, NH and Harom). Found, %: C 74.45; H 5.46; N 7.23.
3. Alekseev, V.N., Kurs kachestvennogo khimicheskogo
polumik-roanaliza (Course of Qualitative Chemical
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DIKUSAR, POTKIN
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 2 2010