A Convenient Synthesis of Novel 1-[2-(Benzimidazol-2-yl)ethoxy]-2,6-diarylpiperidin-4-ones

Article abstract of DOI:10.1081/SCC-120028643

Upon the study of biological evaluation of benzazolylethoxypiperidones, an array of novel benzimidazolylethoxypiperidones were synthesized. 2,6-Diarylpiperidin-4-ones upon strategical N-hydroxylation, cyanoethylation followed by acid aided condensation wi

Full text of DOI:10.1081/SCC-120028643

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A Convenient Synthesis of Novel
1‐[2‐(Benzimidazol‐2‐yl)ethoxy]‐2,6‐diarylpiperidin‐4‐on
C. Ramalingan a , S. Balasubramanian a & S. Kabilan a
a Department of Chemistry , Annamalai University , Annamalainagar, 608 002, India
Published online: 21 Aug 2006.
To cite this article: C. Ramalingan , S. Balasubramanian & S. Kabilan (2004) A Convenient Synthesis of Novel
1‐[2‐(Benzimidazol‐2‐yl)ethoxy]‐2,6‐diarylpiperidin‐4‐ones, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 34:6, 1105-1116, DOI: 10.1081/SCC-120028643
To link to this article: http://dx.doi.org/10.1081/SCC-120028643
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SYNTHETIC COMMUNICATIONSw
Vol. 34, No. 6, pp. 1105–1116, 2004
A Convenient Synthesis of Novel
1-[2-(Benzimidazol-2-yl)ethoxy]-
2,6-diarylpiperidin-4-ones
*
C. Ramalingan, S. Balasubramanian, and S. Kabilan
Department of Chemistry, Annamalai University, Annamalainagar, India
ABSTRACT
Upon the study of biological evaluation of benzazolylethoxypiperidones,
an array of novel benzimidazolylethoxypiperidones were synthesized.
2,6-Diarylpiperidin-4-ones upon strategical N-hydroxylation, cyano-
ethylation followed by acid aided condensation with o-phenylenediamine
afforded a convenient route to novel 1-[2-(benzimidazol-2-yl)ethoxy]-
2,6-diarylpiperidin-4-ones.
Key Words: Cyanoethylation; Piperidine derivatives; Benzimidazole
moiety, Synthetic compounds.
Substituted piperidin-4-ones are important synthetic intermediates for the
preparation of various alkaloids and pharmaceuticals.[1] The piperidine
*
Correspondence: S. Kabilan, Department of Chemistry, Annamalai University,
Annamalainagar-608 002, India; E-mail: kabilan@satyam.net.in.
1105
DOI: 10.1081/SCC-120028643
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

ORDER
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1106
Ramalingan, Balasubramanian, and Kabilan
nucleus can also be frequently recognized in the structure of numerous
naturally occurring alkaloids and synthetic compounds with interesting bio-
logical and pharmacological properties. As a consequence, the development of
general methods for the synthesis of piperidine derivatives has been the
subject of considerable synthetic effort.[2] Benzimidazole (1,3-dideazapurine)
is an important nucleus which has been extensively used in medicinal
chemistry, notable clinical examples being the antihistaminic astemizole and
the antiulcerative omeprazole.[3] Benzimidazoles are marked for their anti-
inflammatory,[4] macrofilaricidal,[5] antibiotic,[6] antiarrythemic,[6] anthel-
mintic,[7] antibacterial,[7] antifungal,[8] antihistaminic,[9] anticancer,[10]
angiotension receptor antagonist,[11] potent and selective 5-HT4 receptor
antagonist,[12] antitumour[13] and antiviral[14] activities. An essential com-
ponent of the search for new leads in a drug designing program is the synthesis
of molecules, which are novel yet resemble known biologically active
molecules by virtue of the presence of some critical structural features.[15] In
the interest of above, we planned to synthesize a system which combines these
two biolabile components together to give a compact structure like title
compounds.
Recently, we exploited the synthesis of 2,6-diarylpiperidin-4-one deriva-
tives with a view to incorporate various other bioactive heterocyclic nucleus
intact for evaluation of their biological importance and also as a reagent for
effecting functional group interconversion.[16]
Cyclic ketones normally undergo Baeyer–Villeger oxidation (oxygen
insertion reaction) to yield lactones upon treatment with peracids.[17] When
2,6-diarylpiperidin-4-ones were subjected to Baeyer–Villeger type of reaction
by using m-CPBA, 1-hydroxy-2,6-diarylpiperidin-4-ones[18] resulted instead
of lactones. On treatment with acrylonitrile, substituted tetrahydrothiopyran-
4-ones containing active hydrogen underwent cyanoethylation yielding 3-[2-
cyanoethoxy]derivatives.[19] In 1-hydroxy-2,6-diarylpiperidin-4-ones, there
are active methylenic hydrogens at C3 and C5. Hence expectation of
cyanoethylation to occur at these positions besides at 1-hydroxyl group is
quite normal. However in all the cases, specifically the 1-hydroxy group alone
underwent cyanoethylation[20] to afford 1-(2-cyanoethoxy)-2,6-diarylpiper-
idin-4-one in good yields (60%–74%) upon treatment with acrylonitrile in the
presence of catalyst triton B. Usually cyanoethylation[21] is a base catalyzed
reaction and invariably requires an alkaline catalyst. But certain amines are
quite exceptional. Oxides, hydroxides, alkoxides, alkali metal hydrides, etc.,
are useful for this purpose. Solubility of the bases in organic solvents should
be taken in to account. Mono or multiple cyanoethylation depends upon the
proper choice of a catalyst with sufficient basicity to remove the labile proton
from the compound undergoing cyanoethylation. Triton B is particularly
employed here on account of its basicity and its solubility in organic media.

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1-[2-(Benzimidazol-2-yl)ethoxy]-2,6-diarylpiperidin-4-ones
1107
Cyanoethylation requires cooling to avoid polymerization of acrylonitrile.
Inert solvents like benzene, dioxane, acetonitrile, or pyridine can be used to
dissolve solid reactants or to moderate the reaction.
1-(2-Cyanoethoxy)-2,6-diarylpiperidin-4-ones upon condensation with o-
phenylenediamine in acid medium resulted 1-[2-(benzimidazol-2-yl)ethoxy]-
2,6-diarylpiperidin-4-ones in moderate yields (40%–62%). Formation of an
iminoyl chloride from the cyanoethylated compound in the presence of HCl is
presumed to be essential for the condensation. The importance of the title
compounds is due to their diverse potential, broad-spectrum biological
activity. The schematic representation and the analytical data of compounds
25–42 are given in Sch. 1 and Table 1, respectively. The spectral character-
ization data for the novel intermediates 25–33 are furnished in Table 2.
Scheme 1.

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Ramalingan, Balasubramanian, and Kabilan
Table 1. Analytical data for compounds 25–42.
Elemental analysis
Yield
(%)
M.P.
(8C)
Entry
R1
R2
R
C (%) H (%) N (%)
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
H
H
H
H
H
70
74
69
65
64
67
69
70
63
60
62
60
40
35
35
52
55
47
87
76
92
71
60
68
80
73
62
128
74.92 6.24
75.39 6.57
75.81 6.89
61.79 4.63
62.62 4.97
63.39 5.28
69.42 6.31
69.96 6.58
70.46 6.85
8.73
8.37
8.04
7.23
6.95
6.72
7.36
7.10
6.87
CH3
CH3
H
CH3
H
H
Cl
H
CH3
CH3
H
Cl
Cl
CH3
H
OCH3
OCH3
OCH3
H
H
CH3
CH3
H
CH3
H
75.93 5.98 10.16
H
CH3
CH3
H
H
107–108 76.20 6.31
9.82
9.50
8.71
8.48
8.24
8.90
8.60
8.39
CH3
H
H
Cl
98
79
76.49 6.56
64.98 4.83
65.58 5.04
66.14 5.28
71.27 6.15
H
CH3
CH3
H
Cl
Cl
92
71–72
113
CH3
H
OCH3
OCH3
OCH3
H
CH3
CH3
CH3
102–103 71.77 6.36
85–86 72.10 6.57
EXPERIMENTAL
The TLC was performed to access the reactions and purity of products.
Melting points were recorded in open capillaries and were uncorrected. IR
spectra were recorded in Perkin–Elmer 297 spectrophotometer in KBr pellets
1
and only noteworthy absorption levels (reciprocal centimeter) are listed. H-
NMR spectra were recorded at 400 MHz on Bruker AMX 400 MHz
spectrophotometer in CDCl3 using TMS as internal standard and 13C-NMR
spectra were recorded at 100 MHz on Bruker AMX 400 MHz spectropho-
tometer in CDCl3. Mass spectra were recorded on a VG analytical 7070E
instrument equipped with VG 11–250 data acquisition system. Satisfactory
microanalysis were obtained on Carlo Erba 1106 and Perkin Elmer models
240 CHN analyzer.
From the literature precedent,[22] 2,6-diarylpiperidin-4-ones (7–15) were
prepared by the condensation of appropriate ketones, aldehydes, and
ammonium acetate in 1 : 2 : 1 ratio.

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1-[2-(Benzimidazol-2-yl)ethoxy]-2,6-diarylpiperidin-4-ones
1109
Table 2. Spectral characterization data for compounds 25–33.
Entry
Spectral characterization data
25
Mass: m/z 320 (Mþ) (M.F. C20H20O2N2), 294, 280, 267, 250, 222, 208, 194,
163, 91, 77 (100%), 65, 53, 51. 1H NMR: d 2.58–2.81 (m, 6H, H3, H5,
OCH2CH2), 3.75 (t, 2H, OCH2CH2), 4.01 (dd, 2H, H2, H6), 7.25–7.46 (m, 10H,
aryl protons). 13C NMR: d 19.623 (OCH2CH2), 51.078 (C3, C5), 65.314 (C2,
;;
C6), 70.123 (OCH2CH2), 124.310 (C N), 124.862, 126.537, 127.131, 146.810
(aryl carbons), 206.310 (C55O).
26
Mass: m/z 334 (Mþ) (M.F. C21H22O2N2), 294, 281, 264, 222, 177, 131, 118,
105, 91, 77 (100%), 65, 53, 51. 1H NMR: d 0.81 (d, 3H, CH3), 2.57–2.84
(m, 5H, H3, H5, OCH2CH2), 3.57 (d, 1H, H2), 3.74 (t, 2H, OCH2CH2), 3.95 (dd,
1H, H6), 7.28–7.48 (m, 10H, aryl protons). 13C NMR: d 10.604 (CH3 at 3),
19.629 (OCH2CH2), 50.908 (C3) 51.592 (C5), 65.625 (C6), 70.131 (OCH2CH2),
;;
71.136 (C2), 124.324 (C N), 124.642 126.312, 126.463, 127.192, 127.560,
139.958, 149.548 (aryl carbons), 207.712 (C55O).
27
28
29
Mass: m/z 348 (Mþ) (M.F. C22H24O2N2), 308, 298, 278, 144, 121, 84, 77
1
(100%), 59, 56, 53. H NMR: d 0.82 (d, 6H, CH3), 2.59 (t, 2H, OCH2CH2),
2.71–2.78 (m, 2H, H3, H5), 3.60 (d, 2H, H2, H6), 3.77 (t, 2H, OCH2CH2), 7.27–
7.53 (m, 10H, aryl protons). 13C NMR: d 10.981 (CH3 at 3), 19.627
(OCH2CH2), 51.210 (C3, C5), 70.123 (OCH2CH2), 71.326 (C2, C6), 124.298
;;
(C N), 124.936, 126.692, 127.252, 147.821 (aryl carbons), 209.448 (C55O).
Mass: m/z 388 (Mþ) (M.F. C20H18O2N2Cl2), 362, 348, 338, 290, 276, 197, 137,
111, 75, 65, 53 (100%), 50. 1H NMR: d 2.58–2.84 (m, 6H, H3, H5, OCH2CH2),
3.76 (t, 2H, OCH2CH2), 4.04 (dd, 2H, H2, H6), 7.30, 7.36 (2d, 8H, aryl protons).
13C NMR: d 19.663 (OCH2CH2), 51.325 (C3, C5), 64.524 (C2, C6), 70.129
;;
(OCH2CH2), 124.410 (C N), 128.054, 128.203, 133.106, 146.538 (aryl
carbons), 204.982 (C55O).
Mass: m/z 402 (Mþ) (M.F. C21H20O2N2Cl2), 362, 349, 304, 290, 239, 196, 152,
1
139, 111, 75, 65, 53 (100%), 50. H NMR: d 0.78 (d, 3H, CH3), 2.59–2.87
(m, 5H, H3, H5, OCH2CH2), 3.64 (d, 1H, H2), 3.76 (t, 2H, OCH2CH2), 4.03 (dd,
1H, H6), 7.32–7.45 (m, 8H, aryl protons). 13C NMR: d 10.712 (CH3 at 3),
19.674 (OCH2CH2), 51.165 (C3) 51.842 (C5), 64.825 (C6), 70.141 (OCH2CH2),
;;
70.524 (C2), 124.372 (C N), 127.186, 128.652, 128.783, 131.243, 131.980,
133.924, 138.911, 146.392 (aryl carbons), 206.204 (C55O).
30
Mass: m/z 416 (Mþ) (M.F. C22H22O2N2Cl2), 376, 363, 318, 207, 183, 155, 111,
1
91, 84, 75, 65, 53 (100%), 50. H NMR: d 0.79 (d, 6H, CH3), 2.61 (t, 2H,
OCH2CH2), 2.73–2.88 (m, 2H, H3, H5), 3.62 (d, 2H, H2, H6), 3.75 (t, 2H,
OCH2CH2), 7.33, 7.39 (2d, 8H, aryl protons). 13C NMR: d 10.870 (CH3 at 3),
19.668 (OCH2CH2), 51.462 (C3, C5), 70.133 (OCH2CH2), 70.526 (C2, C6),
;;
124.640 (C N), 128.216, 128.386, 133.192, 146.738 (aryl carbons), 208.196
(C55O).
(continued)

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Ramalingan, Balasubramanian, and Kabilan
Table 2. Continued.
Entry
Spectral characterization data
31
Mass: m/z 380 (Mþ) (M.F. C22H24O4N2), 340, 327, 282, 254, 193, 133, 107, 75,
65, 53 (100%). 1H NMR: d 2.50–2.79 (m, 6H, H3, H5, OCH2CH2), 3.76 (t, 2H,
OCH2CH2), 3.81 (s, 6H, aryl OCH3), 4.03 (dd, 2H, H2, H6), 6.89, 7.34 (2d, 8H,
aryl protons). 13C NMR: d 19.638 (OCH2CH2), 50.981 (C3, C5), 54.314 (aryl
;;
OCH3), 64.669 (C2, C6), 70.160 (OCH2CH2), 124.432 (C N), 115.532,
127.841, 141.897, 157.874 (aryl carbons), 206.194 (C55O).
32
Mass: m/z 394 (Mþ) (M.F. C23H26O4N2), 354, 341, 296, 207, 192, 148, 107, 75,
1
65, 53 (100%), 50. H NMR: d 0.79 (d, 3H, CH3), 2.51–2.81 (m, 5H, H3, H5,
OCH2CH2), 3.62 (d, 1H, H2), 3.76 (t, 2H, OCH2CH2), 3.81 (s, 6H, aryl OCH3),
4.03 (dd, 1H, H6), 6.84–6.86, 7.35–7.37 (m, 8H, aryl protons). 13C NMR: d
10.608 (CH3 at 3), 19.667 (OCH2CH2), 50.810 (C3) 51.497 (C5), 54.423 (aryl
;;
OCH3), 64.980 (C6), 70.172 (OCH2CH2), 70.548 (C2), 124.278 (C N),
114.380, 115.786, 128.016, 130.943, 134.723, 141.598, 157.271, 159.216 (aryl
carbons), 207.792 (C55O).
33
Mass: m/z 408 (Mþ) (M.F. C24H28O4N2), 368, 355, 310, 204, 151, 133, 107, 84,
75, 59, 53 (100%), 50. 1H NMR: d 0.81 (d, 6H, CH3), 2.61 (t, 2H, OCH2CH2),
2.70–2.87 (m, 2H, H3, H5), 3.62 (d, 2H, H2, H6), 3.77 (t, 2H, OCH2CH2), 3.82
(s, 6H, aryl OCH3), 6.89, 7.36 (2d, 8H, aryl protons). 13C NMR: d 10.897 (CH3
at 3), 19.693 (OCH2CH2), 51.117 (C3, C5), 54.562 (aryl OCH3), 70.166
;;
(OCH2CH2), 71.196 (C2, C6), 124.512 (C N), 115.386, 127.792, 141.898,
158.486 (aryl carbons), 207.430 (C55O).
1-Hydroxy-2,6-diphenylpiperidin-4-one[17] (16)
A solution of 2,6-diphenylpiperidin-4-one (7) (0.005 mol) and m-CPBA
(0.005 mol) in 40 mL of chloroform was stirred for 15 min and allowed to
stand at 208C overnight. The mixture was diluted with chloroform and washed
with 10% sodium bicarbonate solution. The chloroform layer was dried over
anhydrous sodium sulfate and concentrated under reduced pressure.
Purification of the residue by silicagel column chromatography with 8 : 12
benzene-petroleum ether as element yielded the product 16. The compounds
17–24 were prepared similarly.
1-(2-Cyanoethoxy)-2,6-diphenylpiperidin-4-one (25)
A mixture of 1-hydroxy-2,6-diphenylpiperidin-4-one (16) (0.005 mol)
and acrylonitrile (0.005 mol) in 50 mL of 1,4-dioxane was taken in 100 mL

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1-[2-(Benzimidazol-2-yl)ethoxy]-2,6-diarylpiperidin-4-ones
1111
round bottom flask and cooled in an ice bath. A few crystals of resorcinol were
added followed by dropwise addition of triton B (5 mL) with shaking. The
mixture was stirred at 658C–758C for 9 hr during which time some of the
solvent evaporated. After cooling, the resulting solution was poured over
benzene : petroleum ether, 1 : 3 mixture. The solid thus obtained was
recrystallized from methanol to afford 25. The compounds 26–33 were
prepared similarly.
1-[2-(Benzimidazol-2-yl)ethoxy]-2,6-diphenylpiperidin-4-one
(34)
To a mixture of 1-(2-cyanoethoxy)-2,6-diphenylpiperidin-4-one 25
(0.005 mol) and o-phenylenediamine (0.005 mol), dilute hydrochloric acid
(10 cc of conc. HCl in 100 cc of water) was added with constant shaking. Then
the contents of the flask was allowed to reflux in an oil bath for 12 hr. After the
addition of 50 mL of water into to reaction mass, it was filtered to remove
impurities. To isolate 34 as a base, the acid solution was treated with strong
ammonia (15 cc) and was poured into water. The precipitated base was
recrystallized twice from ethanol. IR: cm21 (KBr) 3256, 2942, 2930, 1705.
Mass: m/z 411(Mþ) (M.F.: C26H25N3O2), 320, 294, 280, 267, 250, 222, 208,
194, 163, 144, 117, 103 (100%), 91, 77, 65, 51. 1H-NMR: d 4.04 (dd,
3J ¼ 12.64 Hz; 3.86 Hz, 2H, H2, H6), 2.61–2.85 (m, 6H, H3, H5, –OCH2–
CH2–), 7.27–7.49 (m, 14H, arylprotons), 3.86 (t, J ¼ 6.50 Hz, 2H, –OCH2–
CH2–), 12.83 (br.s, 1H, NH). 13C-NMR: d 69.27 (C2, C6), 49.29 (C3, C5),
206.11 (C55O), 69.31 (–OCH2–CH2–), 19.86 (–OCH2–CH2–), 110.23,
115.01, 115.13, 120.99, 121.01, 127.78, 129.78, 130.72, 137.25 (aryl
carbons), 141.73(C20 , C60 ), 157.15 (C2 of benzimidazole moiety).
The compounds 35–42 were synthesised similarly.
1-[2-(Benzimidazol-2-yl)ethoxy]-2,6-diphenyl-3-
methylpiperidin-4-one (35)
IR: cm21 (KBr) 3250, 2942, 2807, 1695. Mass: m/z 425(Mþ) (M.F.:
C27H27N3O2), 294, 281, 264, 236, 222, 205, 177, 162, 144, 131, 118, 117, 105
(100%), 91, 77, 65, 51. 1H-NMR: d 4.02 (dd, 3J ¼ 13.03 Hz; 3.36 Hz, 1H, H6),
3.59(d, 3J ¼ 11.65 Hz, 1H, H2), 2.60–2.88 (m, 5H, H3, H5, –OCH2–CH2–),
7.28–7.48 (m, 14H, arylprotons), 3.85 (t, J ¼ 6.49 Hz, 2H, –OCH2–CH2–),
0.80 (d, J ¼ 6.54 Hz, 3H, CH3), 12.85 (br.s, 1H, NH). 13C-NMR: d 75.80 (C2),
69.58 (C6), 49.12 (C3), 48.77 (C5), 207.55 (C55O), 69.32 (–OCH2–CH2–),
19.87 (–OCH2–CH2–), 110.20, 115.01, 115.14, 120.98, 121.05, 127.74,

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Ramalingan, Balasubramanian, and Kabilan
127.71, 129.83, 130.59, 130.70, 137.27 (aryl carbons), 140.99 (C20 ), 141.83
(C60 ), 157.16 (C2 of benzimidazole moiety), 10.60 (CH3).
1-[2-(Benzimidazol-2-yl)ethoxy]-2,6-diphenyl-3,5-
dimethylpiperidin-4-one (36)
IR: cm21 (KBr) 3258, 2932, 2848, 1698. Mass: m/z 439 (Mþ) (M.F.:
C28H29N3O2), 308, 295, 278, 250, 173, 144, 121, 118, 117, 103 (100%), 91,
84, 77, 59, 56, 51. 1H-NMR: d 3.62 (d, 3J ¼ 11.66 Hz, 2H, H2, H6), 2.82–2.88
(m, 2H, H3, H5), 2.72 (t, J ¼ 6.52 Hz, 2H, –OCH2–CH2–), 7.27–7.54
(m, 14H, arylprotons), 3.86 (t, J ¼ 6.50 Hz, 2H, –OCH2–CH2–), 0.81
(d, J ¼ 6.58 Hz, 6H, CH3), 12.92 (br.s, 1H, NH). 13C-NMR: d 76.03 (C2, C6),
49.42 (C3, C5), 209.21 (C55O), 69.32 (–OCH2–CH2–), 19.87 (–OCH2–
CH2–), 110.19, 115.02, 115.14, 120.99, 121.03, 127.85, 129.80, 130.66,
137.24 (aryl carbons), 141.10 (C20 , C60 ), 157.14 (C2 of benzimidazole moiety),
10.98 (CH3).
1-[2-(Benzimidazol-2-yl)ethoxy]-2,6-
bis(p-chlorophenyl)piperidin-4-one (37)
IR: cm21 (KBr) 3224, 2927, 2792, 1708. Mass: m/z 479 (Mþ) (M.F.:
C26H23N3O2Cl2), 388, 362, 348, 335, 318, 290, 276, 262, 197, 167, 145, 137,
1
3
117, 111, 91, 75, 65, 53 (100%), 50. H-NMR: d 4.07 (dd, J ¼ 12.64 Hz;
3.87 Hz, 2H, H2, H6), 2.60–2.89 (m, 6H, H3, H5, –OCH2–CH2–), 7.29–7.53
(m, 12H, arylprotons), 3.86 (t, J ¼ 6.50 Hz, 2H, –OCH2–CH2–), 12.89 (br.s,
1H, NH). 13C-NMR: d 68.48 (C2,C6), 48.96 (C3, C5), 205.11 (C55O), 69.32
(–OCH2–CH2–), 19.88 (–OCH2–CH2–), 110.24, 115.03, 115.14, 120.99,
121.05, 129.01, 129.99, 137.27 (aryl carbons), 134.92 (C20000, C60000), 139.88 (C20 ,
C60 ), 157.20 (C2 of benzimidazole moiety).
1-[2-(Benzimidazol-2-yl)ethoxy]-2,6-bis(p-chlorophenyl)-3-
methylpiperidin-4-one (38)
IR: cm21 (KBr) 3220, 2961, 2857, 2728, 1694. Mass: m/z 493 (Mþ)
(M.F.: C27H25N3O2Cl2), 362, 349, 332, 304, 290, 239, 211, 196, 165, 152,
145, 139, 131, 117, 111, 91, 75, 53 (100%), 50. 1H-NMR: d 4.06 (dd,
3J ¼ 13.02 Hz; 3.36 Hz, 1H, H6), 3.68 (d, 3J ¼ 11.64 Hz, 1H, H2), 2.61–2.90
(m, 5H, H3, H5, –OCH2–CH2–), 7.18–7.51 (m, 12H, arylprotons), 3.86
(t, J ¼ 6.50 Hz, 2H, –OCH2–CH2), 0.79(d, J ¼ 6.58 Hz, 3H, CH3), 12.85

ORDER
REPRINTS
1-[2-(Benzimidazol-2-yl)ethoxy]-2,6-diarylpiperidin-4-ones
1113
(br.s, 1H, NH). 13C-NMR: d 75.00 (C2), 68.86 (C6), 48.82 (C3), 48.46 (C5),
206.24 (C55O), 69.33 (–OCH2–CH2–), 19.88 (–OCH2–CH2–), 110.21,
115.01, 115.14, 121.00, 121.10, 129.37, 129.38, 129.86, 129.99, 137.30 (aryl
carbons), 134.74 (C20000), 134.90 (C60000), 139.10 (C20 ), 139.97 (C60 ), 157.16 (C2 of
benzimidazole moiety), 10.70 (CH3).
1-[2-(Benzimidazol-2-yl)ethoxy]-2,6-bis(p-chlorophenyl)-3,5-
dimethyl piperidin-4-one (39)
IR: cm21 (KBr) 3217, 2958, 2841, 2798, 1695. Mass: m/z 507 (Mþ)
(M.F.: C28H27N3O2Cl2), 376, 363, 346, 318, 207, 183, 155, 145, 137, 117,
1
3
111, 91, 75, 59, 53 (100%), 50. H-NMR: d 3.65 (d, J ¼ 11.66 Hz, 2H, H2,
H6), 2.83–2.89 (m, 2H H3, H5), 2.73 (t, J ¼ 6.53 Hz, 2H, –OCH2–CH2–),
7.31–7.53 (m, 12H, arylprotons), 3.86 (t, J ¼ 6.49 Hz, 2H, –OCH2–CH2–),
0.80 (d, J ¼ 6.61 Hz, 6H, CH3), 12.96 (br.s, 1H, NH). 13C-NMR: d 75.29 (C2,
C6), 49.18 (C3, C5), 208.23 (C55O), 69.30 (–OCH2–CH2–), 19.87 (–OCH2–
CH2–), 110.20, 115.02, 115.15, 121.00, 121.04, 129.24, 129.84, 137.25 (aryl
carbons), 134.82 (C20000, C60000), 139.12 (C20 , C60 ), 157.58 (C2 of benzimidazole
moiety), 10.87 (CH3).
1-[2-(Benzimidazol-2-yl)ethoxy]-2,6-bis(p-
methoxyphenyl)piperidin-4-one (40)
IR: cm21 (KBr) 3235, 2942, 2830, 2787, 1704. Mass: m/z 471(Mþ)
(M.F.: C28H29N3O4), 380, 354, 340, 327, 310, 282, 268, 254, 193, 167, 144,
133, 117, 107, 91, 75, 65, 53 (100%), 50. 1H-NMR: d 4.06 (dd, 3J ¼ 12.65 Hz;
3.85 Hz, 2H, H2, H6), 2.58–2.84 (m, 6H, H3, H5, –OCH2–CH2–), 6.88; 7.21–
7.52 (d, 4H; m, 8H, arylprotons), 3.85 (t, J ¼ 6.52 Hz, 2H, –OCH2–CH2–),
3.81 (s, 6H, OCH3), 12.83 (br.s, 1H, NH). 13C-NMR: d 68.63 (C2, C6), 49.38
(C3, C5), 206.20 (C55O), 69.40 (–OCH2–CH2–), 19.84 (–OCH2–CH2–),
110.28, 114.50, 115.06, 115.20, 120.06, 121.10, 132.99, 137.34 (aryl
carbons), 158.81 (C20000, C60000), 135.55 (C20 , C60 ), 157.34 (C2 of benzimidazole
moiety), 55.01 (OCH3).
1-[2-(Benzimidazol-2-yl)ethoxy]-2,6-bis(p-methoxyphenyl)-3-
methyl piperidin-4-one (41)
IR: cm21 (KBr) 3238, 2950, 2847, 1699. Mass: m/z 485 (Mþ) (M.F.:
C29H31N3O4), 354, 341, 324, 296, 282, 265, 207, 192, 161, 148, 131, 117, 107,

ORDER
REPRINTS
1114
Ramalingan, Balasubramanian, and Kabilan
91, 75, 65, 53 (100%), 50. 1H-NMR: d 4.05 (dd, 3J ¼ 12.99 Hz: 3.33 Hz, 1H,
3
H6), 3.66 (d, J ¼ 11.67 Hz, 1H, H2), 2.58–2.87 (m, 5H, H3, H5, –OCH2–
CH2–), 6.87; 7.26–7.51 (d, 4H; m, 8H, arylprotons), 3.85 (t, J ¼ 6.52 Hz, 2H,
–OCH2–CH2–), 3.80 (s, 6H, OCH3), 0.80 (d, J ¼ 6.54 Hz, 3H, CH3), 12.75
(br.s, 1H, NH). 13C-NMR: d 75.18 (C2), 69.00 (C6), 49.21 (C3), 48.88 (C5),
207.42 (C55O), 69.43 (–OCH2–CH2–), 19.87 (–OCH2–CH2–), 110.20,
114.89, 114.97, 114.98, 120.99, 121.00, 132.98, 133.11, 137.35 (aryl
carbons), 158.56 (C20000), 158.95 (C60000), 135.13 (C20 ), 135.83 (C60 ), 157.16 (C2 of
benzimidazole moiety), 10.61 (CH3).
1-[2-(Benzimidazol-2-yl)ethoxy]-2,6-bis(p-methoxyphenyl)-
3,5-dimethyl piperidin-4-one (42)
IR: cm21 (KBr) 3227, 2927, 2848, 1697. Mass: m/z 499 (Mþ) (M.F.:
C30H33N3O4), 368, 355, 338, 310, 204, 179, 151, 145, 133, 117, 107, 91, 84,
75, 53 (100%), 50. 1H-NMR: d 3.64 (d, 3J ¼ 11.69 Hz, 2H, H2, H6), 2.81–2.87
(m, 2H, H3, H5), 2.72 (t, J ¼ 6.51 Hz, 2H, –OCH2–CH2–), 6.87; 7.25–7.51
(d, 4H; m, 8H, arylprotons), 3.86 (t, J ¼ 6.50 Hz, 2H, –OCH2–CH2–), 3.81
(s, 6H, OCH3), 12.94 (br.s, 1H, NH), 0.81 (d, J ¼ 6.57 Hz, 6H, CH3). 13C-
NMR: d 75.46 (C2, C6), 49.54 (C3, C5), 209.43 (C55O), 69.31 (–OCH2–
CH2–), 19.89 (–OCH2–CH2–), 110.00, 114.13, 114.97, 115.00, 120.98,
120.99, 133.20, 137.25 (aryl carbons), 158.88 (C20000, C60000), 135.11 (C20 , C60 ),
157.56 (C2 of benzimidazole moiety), 55.21 (OCH3), 10.97 (CH3).
ACKNOWLEDGMENT
The authors are grateful to Prof. K. Pandiarajan, Head, Department of
Chemistry, Annamalai University for providing needed facilities. One of the
authors, S.K., is grateful to University Grants Commission, New Delhi for
financial support. SB wishes to thank Council of Scientific & Industrial
Research, New Delhi for the award of Senior Research Fellowship.
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Received in India September 11, 2003

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